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<journal-id journal-id-type="publisher-id">Front. Pharmacol.</journal-id>
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<journal-title>Frontiers in Pharmacology</journal-title>
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<issn pub-type="epub">1663-9812</issn>
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<article-id pub-id-type="publisher-id">1651219</article-id>
<article-id pub-id-type="doi">10.3389/fphar.2025.1651219</article-id>
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<subject>Review</subject>
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<title-group>
<article-title>Advances in traditional Chinese medicine for burn treatment: mechanisms, therapeutic approaches, and innovative preparations</article-title>
<alt-title alt-title-type="left-running-head">Liu et al.</alt-title>
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<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fphar.2025.1651219">10.3389/fphar.2025.1651219</ext-link>
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<surname>Liu</surname>
<given-names>Ying</given-names>
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<xref ref-type="aff" rid="aff1">
<sup>1</sup>
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<surname>Yu</surname>
<given-names>Caiyuan</given-names>
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<surname>Dou</surname>
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<surname>Li</surname>
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<surname>Liu</surname>
<given-names>Mengyan</given-names>
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<surname>Zeng</surname>
<given-names>Weijia</given-names>
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<surname>Feng</surname>
<given-names>Zizhao</given-names>
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<surname>Huang</surname>
<given-names>Ming</given-names>
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<surname>Zhu</surname>
<given-names>Yizhun</given-names>
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<aff id="aff1">
<label>1</label>
<institution>School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology</institution>, <city>Taipa</city>, <country country="CN">Macao SAR, China</country>
</aff>
<aff id="aff2">
<label>2</label>
<institution>School of Pharmacy, Guangzhou Xinhua University</institution>, <city>Guangzhou</city>, <country country="CN">China</country>
</aff>
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<label>3</label>
<institution>School of Pharmacy, Sun Yat-sen University</institution>, <city>Guangzhou</city>, <country country="CN">China</country>
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<author-notes>
<corresp id="c001">
<label>&#x2a;</label>Correspondence: Ying Liu, <email xlink:href="yingliu@xhsysu.cn">yingliu@xhsysu.cn</email>; Yizhun Zhu, <email xlink:href="yzzhu@must.edu.mo">yzzhu@must.edu.mo</email>
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<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2025-11-17">
<day>17</day>
<month>11</month>
<year>2025</year>
</pub-date>
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<year>2025</year>
</pub-date>
<volume>16</volume>
<elocation-id>1651219</elocation-id>
<history>
<date date-type="received">
<day>21</day>
<month>06</month>
<year>2025</year>
</date>
<date date-type="rev-recd">
<day>09</day>
<month>10</month>
<year>2025</year>
</date>
<date date-type="accepted">
<day>10</day>
<month>10</month>
<year>2025</year>
</date>
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<permissions>
<copyright-statement>Copyright &#xa9; 2025 Liu, Yu, Dou, Shen, Li, Liu, Xie, Zeng, Feng, Huang and Zhu.</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Liu, Yu, Dou, Shen, Li, Liu, Xie, Zeng, Feng, Huang and Zhu</copyright-holder>
<license>
<ali:license_ref start_date="2025-11-17">https://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p>
</license>
</permissions>
<abstract>
<p>Traditional Chinese Medicine (TCM) possesses a well-documented historical legacy and substantial clinical experience in treating burn injuries and diverse wound conditions. Grounded in TCM theory, therapeutic strategies incorporate herbal medicine and its external preparations, as well as TCM auxiliary treatment, forming a comprehensive treatment framework. A systematic evaluation of burn management, particularly recent advancements in TCM research, carries significant implications for both theoretical and clinical applications. This paper synthesizes information from a plethora of online resources to explicate the mechanisms of TCM in burn treatment from multifaceted perspectives. Specifically, a comprehensive collection of literature pertaining to TCM burn treatment from the past three&#xa0;decades was amassed from electronic databases including PubMed, CNKI, and Web of Science. A meticulous keyword information statistical analysis was performed on this corpus. The search strategy employed keyword clusters such as &#x201c;traditional Chinese medicine, phytochemistry, or herbs&#x201d; combined with &#x201c;burn, scald, or skin wound&#x201d;. The scientific nomenclature of plants was verified using &#x201c;The Plant List&#x201d; (<ext-link ext-link-type="uri" xlink:href="http://www.plantsoftheworldonline.org">www.plantsoftheworldonline.org</ext-link>). This review encapsulates the methodologies of burn treatment within TCM and underscores a multitude of herbs with burn-treating capabilities, including <italic>Arnebia euchroma</italic> (Royle ex Benth.) I.M.Johnst., <italic>Rheum palmatum</italic> L.<italic>, Coptis chinensis</italic> Franch., <italic>Phellodendron chinense</italic> C.K.Schneid., <italic>Sanguisorba officinalis</italic> L., and <italic>Angelica sinensis</italic> (Oliv.) Diels<italic>,</italic> as well as natural borneol (from <italic>Dryobalanops aromatica</italic> C.F.Gaertn.), Frankincense (from <italic>Boswellia sacra</italic> Fl&#xfc;ck.), and Myrrh (from <italic>Commiphora myrrha</italic> (T.Nees) Engl.). The principal active ingredients identified are shikonin, emodin, berberine, ferulic acid, and curcumin; however, their mechanisms warrant further in-depth investigation. Notable strides have been made in the innovation and research of TCM in burn treatment. Beyond traditional external formulations, hydrogel, liposome, microsphere, and nanofibers have emerged as pivotal elements in burn management. These advanced materials have introduced an innovative drug delivery system by integrating the active components, thereby enhancing the efficacy of burn treatment.</p>
</abstract>
<abstract abstract-type="graphical">
<title>Graphical Abstract</title>
<p>
<fig>
<graphic xlink:href="FPHAR_fphar-2025-1651219_wc_abs.tif" position="anchor">
<alt-text content-type="machine-generated">Circular infographic illustrating traditional Chinese medicine (TCM) for burn injury treatment. The center features an image of a burn injury surrounded by medicinal plants like Coptis chinensis, Frankincense, and Myrrh. Various forms of treatments are listed, including ointments, oils, powders, and hydrogels. Around the circle, the effects on biological processes are indicated, such as reduced inflammation and enhanced tissue growth. The layout is divided into concentric rings, linking each plant with its treatment form and biological effect.</alt-text>
</graphic>
</fig>
</p>
</abstract>
<kwd-group>
<kwd>traditional Chinese medicine</kwd>
<kwd>burn injury</kwd>
<kwd>active ingredients</kwd>
<kwd>mechanism</kwd>
<kwd>preparation</kwd>
</kwd-group>
<funding-group>
<award-group id="gs1">
<funding-source id="sp1">
<institution-wrap>
<institution>Macau University of Science and Technology Foundation</institution>
<institution-id institution-id-type="doi" vocab="open-funder-registry" vocab-identifier="10.13039/open_funder_registry">10.13039/501100011322</institution-id>
</institution-wrap>
</funding-source>
</award-group>
<funding-statement>The author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by Macau Science and Technology Development fund (FDCT (0012/2021/AMJ, 003/2022/ALC, 0092/2022/A2,0144/2022/A3)). Shenzhen-Hong Kong-Macao Science and Technology Fund (Category C: SGDX20220530111203020). Guangdong Province&#x2019;s Special Fund for Science and Technology Innovation Strategy (pdjh2024a523).</funding-statement>
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<meta-name>section-in-acceptance</meta-name>
<meta-value>Ethnopharmacology</meta-value>
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</front>
<body>
<sec sec-type="intro" id="s1">
<title>Introduction</title>
<p>Burns represent a prevalent form of accidental injury in clinical practice, with an estimated 70 million cases occurring globally each year. These injuries result in approximately 18 million disabilities and over 20,000 deaths annually (<xref ref-type="bibr" rid="B62">Peck, 2011</xref>; <xref ref-type="bibr" rid="B63">2012</xref>). Burns are caused by thermal, electrical, radiation, chemical (acids, alkalis, irritants, and corrosive substances), or other physical and chemical factors, leading to damage and necrosis of superficial and subcutaneous tissues, accompanied by a cascade of pathological changes (<xref ref-type="bibr" rid="B36">Jeschke et al., 2020</xref>). The efficacy of burn treatment depends on the extent and severity of the injury, as well as the timeliness and precision of therapeutic interventions (<xref ref-type="bibr" rid="B71">Radzikowska-B&#xfc;chner et al., 2023</xref>). Conventional treatments often include antibiotics, energy supplements, micronutrients, immune-modulating agents, and topical growth factors or recombinant human growth hormone therapy. However, these treatments may carry potential side effects, such as disruptions to metabolic processes, induction of secondary diseases, or drug dependence (<xref ref-type="bibr" rid="B73">Roshangar et al., 2019</xref>; <xref ref-type="bibr" rid="B55">Markiewicz-Gospodarek et al., 2022</xref>).</p>
<p>Traditional Chinese Medicine (TCM) has a long history of treating burns, with the earliest records dating back to the <italic>Fifty-Two Diseases Prescriptions</italic> from the pre-Qin period in recent years, TCM has gained increasing recognition in burn management due to its notable efficacy, low toxicity, and diverse formulation types (<xref ref-type="bibr" rid="B125">Zhou et al., 2024</xref>). Despite this, there is a notable lack of comprehensive reviews on TCM approaches to burn treatment. Despite this, there is a notable lack of comprehensive reviews on TCM approaches to burn treatment. The existing literature on this topic often remains at the overview level (<xref ref-type="bibr" rid="B40">Kopp et al., 2003</xref>; <xref ref-type="bibr" rid="B32">Herman and Herman, 2020</xref>; <xref ref-type="bibr" rid="B59">Mrabti et al., 2022</xref>), and more detailed studies exploring the underlying mechanisms are still needed. Furthermore, reviews that integrate modern medical methodologies with TCM strategies or explore burn treatment from a contemporary TCM perspective are currently limited.</p>
<p>To address this research gap, a systematic and comprehensive literature review was conducted to evaluate the current application of TCM in burn treatment. The literature search was performed across multiple electronic databases, including PubMed, CNKI, and Web of Science. The search strategy utilized the following keyword clusters: (&#x201c;traditional Chinese medicine&#x201d; OR &#x201c;phytochemistry&#x201d; OR &#x201c;herbs&#x201d;) AND (&#x201c;burn&#x201d; OR &#x201c;scald&#x201d; OR &#x201c;skin wound&#x201d;). The scientific nomenclature of medicinal plants was verified using &#x201c;The Plant List&#x201d; (<ext-link ext-link-type="uri" xlink:href="http://www.plantsoftheworldonline.org">www.plantsoftheworldonline.org</ext-link>). The initial search yielded 92 records from PubMed, 256,153 from CNKI, and an unspecified number from Web of Science. After importing all records into EndNote literature management software (<ext-link ext-link-type="uri" xlink:href="https://endnote.com/">https://endnote.com/</ext-link>), 75 duplicates were removed. The remaining articles underwent a two-stage screening process based on the following criteria: Inclusion Criteria: Studies focused on the use of TCM compounds, single herbs, or active ingredients in the treatment of burns, scalds, or skin wounds. Articles published in peer-reviewed journals within the past 30 years. Reports available in either English or Chinese. Studies involving <italic>in vitro</italic>, <italic>in vivo</italic>, or clinical evaluations. Exclusion Criteria: Publications not relevant to TCM or burn treatment (e.g., veterinary use, non-therapeutic research). Non-original research articles such as editorials, commentaries, or conference abstracts without full text.</p>
<p>After title and abstract screening, irrelevant studies were excluded manually. Ultimately, 109 articles met the inclusion criteria and were selected for in-depth analysis. Additionally, 20 supplementary literatures were included to provide foundational context: 8 pertaining to general burn overviews, 6 related to wound healing mechanisms, and 6 focused on TCM auxiliary therapies. The literature selection process is summarized in <xref ref-type="fig" rid="F1">Figure 1</xref>.</p>
<fig id="F1" position="float">
<label>FIGURE 1</label>
<caption>
<p>Flowchart for inclusion and exclusion of literature in this review.</p>
</caption>
<graphic xlink:href="fphar-16-1651219-g001.tif">
<alt-text content-type="machine-generated">Flowchart depicting a literature review process. Records identified: PubMed (92), CNKI (256), Web of Science (153). Records excluded before screening: 75 duplicates. Records screened: 426. Records excluded due to titles: 235. Reports screened: 191. Reports excluded for irrelevant abstracts and texts: 82. Reports screened again: 109. Other literatures include overview of burns (8), wound healing (6), TCM auxiliary treatment (6). All references for the review: 129.</alt-text>
</graphic>
</fig>
<p>This paper summarizes the understanding of burns in TCM and modern medicine, particularly focused on underlying mechanisms, therapeutic approaches, innovative external preparations, and TCM auxiliary therapies, aims to provide valuable insights and research directions regarding therapeutic drugs for burn management.</p>
<sec id="s1-1">
<title>Burn pathology in modern medicine</title>
<p>Burn injuries are classified into four degrees (I&#x2013;IV) based on the depth and extent of tissue damage (<xref ref-type="bibr" rid="B97">Warby and Maani, 2023</xref>). Superficial burns (first-degree or superficial second-degree) affect only the epidermis, typically healing with minimal scarring. Deep second-degree burns involve the deep dermal layer, presenting with blisters, a red-white base, and increased exudate, often leading to hypertrophic scarring. Third-degree burns extend through the entire dermis, usually requiring surgical intervention, while fourth-degree burns involve deeper structures such as muscle or bone, resulting in significant functional impairment (<xref ref-type="bibr" rid="B127">&#x17b;wiere&#x142;&#x142;o et al., 2023</xref>).</p>
<p>Wound healing aims to restore tissue integrity and homeostasis through three overlapping phases: inflammation, proliferation, and remodeling. Disruptions in these phases can lead to delayed healing or chronic wounds (<xref ref-type="bibr" rid="B91">Wallace et al., 2023</xref>; <xref ref-type="bibr" rid="B64">Pena and Martin, 2024</xref>). Inflammatory Phase initiated by immune responses to remove damaged tissue and pathogens, this phase involves vascular and cellular responses. Cytokines such as transforming growth factor (TGF-&#x3b2;), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), and interleukin-8 (IL-8) are released, recruiting neutrophils and macrophages for pathogen clearance, inflammation resolution, and tissue repair (<xref ref-type="bibr" rid="B13">Childs and Murthy, 2017</xref>; <xref ref-type="bibr" rid="B98">Wilkinson and Hardman, 2020</xref>). The proliferative phase occurs 2&#x2013;10 days post-injury, this phase is driven by macrophages, which release growth factors to recruit fibroblasts and keratinocytes. Angiogenesis, mediated by vascular endothelial growth factor (VEGF) and FGF, is initiated, and fibroblasts synthesize extracellular matrix (ECM) proteins to form granulation tissue (<xref ref-type="bibr" rid="B23">G El Baassiri et al., 2023</xref>). Finally, remodeling phase begins 2&#x2013;3&#xa0;weeks post-injury and lasting up to 2&#xa0;years, this phase involves the maturation of the scar. Fibroblasts, macrophages, and endothelial cells secrete matrix metalloproteinases (MMPs) to degrade type III collagen, which is replaced by type I collagen organized into parallel fibrils. Apoptosis of excess cells and remodeling of the epidermis, vasculature, and nerves occur during this stage (<xref ref-type="bibr" rid="B56">Mathew-Steiner et al., 2021</xref>). Effective wound healing relies on growth factors, nutrient supply, cell-to-cell interactions, and oxygen availability. Disruptions due to infection, malnutrition, chronic diseases, or diabetes can impair healing, leading to chronic wounds. Understanding these mechanisms is critical for optimizing burn treatment strategies (<xref ref-type="fig" rid="F2">Figure 2</xref>).</p>
<fig id="F2" position="float">
<label>FIGURE 2</label>
<caption>
<p>Burn pathology in modern medicine.</p>
</caption>
<graphic xlink:href="fphar-16-1651219-g002.tif">
<alt-text content-type="machine-generated">Diagram showing wound healing progress with four stages: Hemostasis, Inflammation, Proliferation, and Remodeling. It illustrates cellular and molecular interactions at each phase. Accompanying visuals depict the pharmacological effects of Traditional Chinese Medicine (TCM) on burns and scalds, highlighting antibacterial, anti-inflammatory, pain relief, skin growth promotion, apoptosis inhibition, cell proliferation, antioxidant effects, and scar inhibition.</alt-text>
</graphic>
</fig>
</sec>
<sec id="s1-2">
<title>TCM perspective on burn</title>
<p>In TCM, burn injury is collectively referred to as &#x201c;water and fire burns&#x201d;. It occurs when the skin and deeper tissues are exposed to high temperatures, leading to Qi and blood stagnation and an imbalance between defensive (Wei) Qi and nourishing (Ying) Qi. The pathogenesis involves heat acting on the superficial muscles, causing local Qi stagnation and meridian obstruction. This weakens the Wei Qi, the body&#x2019;s first line of defense, reducing its protective function and resulting in fluid leakage, blister formation, and exudate (<xref ref-type="bibr" rid="B69">Que et al., 2005</xref>). Excessive blistering may deplete Yin fluids, eventually leading to Yin deficiency, Yang collapse, and an imbalance between Yin and Yang (<xref ref-type="bibr" rid="B72">Ripszky Totan et al., 2022</xref>). Furthermore, the invasion of fire toxins can impair the functions of the spleen, kidney, and heart, exacerbating Qi stagnation. Sleep disorders in burn patients are closely associated with Yin-Yang imbalances and internal organ dysfunctions (<xref ref-type="bibr" rid="B46">Liang et al., 2021</xref>; <xref ref-type="bibr" rid="B49">Liu et al., 2023</xref>). In TCM, normal sleep relies on the harmonious coordination of Yin-Yang and mental tranquility. Disruptions in these factors or mental unrest can lead to sleep disturbances (<xref ref-type="bibr" rid="B61">O&#x27;Brien and Weber, 2016</xref>). Burn patients often experience severe nocturnal skin itching, which disrupts sleep and may result in neurasthenia or other health complications (<xref ref-type="bibr" rid="B14">Chung et al., 2020</xref>) (<xref ref-type="fig" rid="F3">Figure 3</xref>).</p>
<fig id="F3" position="float">
<label>FIGURE 3</label>
<caption>
<p>TCM perspective on burn injury.</p>
</caption>
<graphic xlink:href="fphar-16-1651219-g003.tif">
<alt-text content-type="machine-generated">Illustration of burns and scalds mechanism in Traditional Chinese Medicine (TCM). It depicts deficiency of Qi in heart and lung, disharmony of nutrient-defensive qi, itching and pain, and sleep dysregulation. The graphic shows stages of burns and scalds with varying redness and tissue loss. It explains heat impairing yin, disrupting yin-yang balance, and factors like dampness evil, stasis evil, and fire evil affecting health. Elements like heart, kidney, spleen, and toxins are included to show their interactions, with arrows indicating connections.</alt-text>
</graphic>
</fig>
<p>Based on the fundamental tenets of TCM, burn injuries can be classified into three distinct stages according to their typical symptomatic manifestations: the stage of excessive heat - toxin accumulation, the stage of Yin - fluid depletion, and the stage of Yin deficiency. These stages often exhibit overlapping pathological features. In the early stage, treatment predominantly focuses on heat-clearing and detoxification strategies to prevent the intrusion of toxins into the body. In the middle stage, the emphasis lies in nourishing Yin, promoting blood generation, clearing heat toxins, and facilitating tissue regeneration. In the late stage, the focus is on Qi supplementation, blood nourishing, and regulating the balance of Qi and blood.</p>
</sec>
<sec id="s1-3">
<title>Treatment of burn with Chinese herbal medicine</title>
<p>With the advancement of modern TCM, there is a growing body of theoretical and practical evidence supporting its use in burn treatment. TCM employs a holistic approach, utilizing single herbs (e.g., <italic>Rheum palmatum</italic> L.), <italic>Coptis chinensis</italic> Franch., <italic>Angelica sinensis</italic> (Oliv.) Diels) and compound prescriptions to address both systemic and local symptoms of burn injuries. Therapeutic methods include internal administration, which regulates systemic conditions and enhances the body&#x2019;s resistance to pathogens, and external application, which directly targets the burn site to promote wound healing and prevent complications such as tissue necrosis, vascular occlusion, and infection. External medications, including ointments, sprays, and hydrogels, play a critical role in addressing local blood circulation disorders and controlling wound infections. Additionally, auxiliary TCM therapies such as acupuncture, cupping, guasha, tuina, and aromatherapy provide complementary benefits by improving blood flow, reducing pain, and enhancing overall recovery (<xref ref-type="fig" rid="F4">Figure 4</xref>).</p>
<fig id="F4" position="float">
<label>FIGURE 4</label>
<caption>
<p>Treatment of burn injury with TCM and modern medical.</p>
</caption>
<graphic xlink:href="fphar-16-1651219-g004.tif">
<alt-text content-type="machine-generated">Flowchart illustrating burn injury treatments categorized into Traditional Chinese Medicine (TCM) and modern medicine. TCM includes TCM drugs, TCM formulae, and other traditional therapies like acupuncture and cupping. Modern medicine involves topical antibacterial drugs, wound dressings, physiotherapy, stem cell therapy, and surgery.</alt-text>
</graphic>
</fig>
<p>Chinese herbal medicine and natural products are widely recognized for their efficacy, low side effects, and minimal resistance development in treating burns. The healing process of burn wounds is highly complex, involving growth factors, inflammatory mediators, and ECM remodeling. TCM exerts its therapeutic effects through multi-component, multi-target, and multi-pathway mechanisms. Experimental studies have demonstrated that products used in TCM can enhance the production and secretion of growth factors, including VEGF and EGF. Additionally, they have been shown to reduce the expression of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-&#x3b1;), inhibit bacterial proliferation, improve immune function, and regulate collagen synthesis along with ECM remodeling. Furthermore, TCM-based treatments exhibit antioxidant properties, eliminate free radicals, facilitate cell proliferation, inhibit apoptosis, and provide analgesic and antipruritic effects.</p>
<p>This review highlights the active ingredients, traditional uses, pharmacological actions, target functions, and mechanisms of commonly used Chinese herbal medicine, underscoring their potential in modern burn treatment strategies (<xref ref-type="table" rid="T1">Table 1</xref>).</p>
<table-wrap id="T1" position="float">
<label>TABLE 1</label>
<caption>
<p>Commonly used Chinese herbal medicine for treating burns.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="center">Chinese herbal medicine</th>
<th align="center">Origin and medicinal parts</th>
<th align="center">Active ingredients</th>
<th align="center">Traditional use</th>
<th align="center">Pharmacological action</th>
<th align="center">Target function</th>
<th align="center">Mechanism</th>
<th align="center">References</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="center">Radix arnebiae (Zi Cao)</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx1.tif"/>
<italic>Arnebia euchroma</italic> (Royle) Johnst Rhizoma</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx2.tif"/>Shikonin</td>
<td align="center">Cool blood and promote blood circulation<break/>Clear internal heat<break/>Neutralize toxins</td>
<td align="center">Anti-inflammatory<break/>Wound healing<break/>Promotes epithelial regeneration</td>
<td align="center">TGF-&#x3b2;1/PI3K/Akt<break/>NF-&#x3ba;B<break/>Wnt4<break/>Bax/Bcl-2</td>
<td align="center">&#x2191;SOD activity<break/>&#x2193;MDA<break/>&#x2193;IL-6/IL-1&#x3b2;/TNF-&#x3b1;<break/>&#x2191;VEGF/EGF/TGF-&#x3b2;<break/>Activates Wnt pathway<break/>Inhibits NF-&#x3ba;B</td>
<td align="center">
<xref ref-type="bibr" rid="B79">Shu et al. (2022)</xref>, <xref ref-type="bibr" rid="B84">Sun et al. (2022)</xref>, <xref ref-type="bibr" rid="B101">Wu T. et al. (2022)</xref>, <xref ref-type="bibr" rid="B24">Gao et al. (2023)</xref>
</td>
</tr>
<tr>
<td align="center">Rhubarb (Da Huang)</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx3.tif"/>
<italic>Rheum palmatum</italic> L. Rhizoma</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx4.tif"/>Emodin Rhubarb-derived characoal</td>
<td align="center">Eliminate heat toxins<break/>Remove accumulations and stagnations<break/>Promote circulation of blood stasis</td>
<td align="center">Anti-inflammatory<break/>Antimicrobial<break/>Promotes collagen synthesis</td>
<td align="center">TLR4/NF-&#x3ba;B<break/>AMPK/mTOR<break/>Notch/TGF-&#x3b2;</td>
<td align="center">&#x2191;SOD<break/>&#x2193;oxidative stress<break/>Inhibits NF-&#x3ba;B<break/>Modulates AMPK pathway to reduce fibrosis<break/>
</td>
<td align="center">
<xref ref-type="bibr" rid="B87">Tang et al. (2007)</xref>, <xref ref-type="bibr" rid="B74">S&#xe1;nchez et al. (2020)</xref>, <xref ref-type="bibr" rid="B94">Wang et al. (2023)</xref>, <xref ref-type="bibr" rid="B86">Tan et al. (2024)</xref>
</td>
</tr>
<tr>
<td align="center">Angelica sinensis (Dang Gui)</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx5.tif"/>
<italic>Angelica sinensis</italic> (Oliv.) Diels Root</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx6.tif"/>Ferulic acid Polysaccharides</td>
<td align="center">Blood-nourishing and circulation-activating<break/>Menstruation-regulating and pain-relieving<break/>Intestine-moistening and laxative</td>
<td align="center">Anti-inflammatory<break/>Angiogenesis<break/>Collagen synthesis Promotes re-epithelialization</td>
<td align="center">p38/JNK1/2<break/>VEGF</td>
<td align="center">&#x2191;HUVEC proliferation<break/>&#x2191;type I collagen</td>
<td align="center">
<xref ref-type="bibr" rid="B42">Lam et al. (2008)</xref>, <xref ref-type="bibr" rid="B118">Zhao et al. (2012)</xref>, <xref ref-type="bibr" rid="B90">Tsai et al. (2016)</xref>, <xref ref-type="bibr" rid="B44">Li et al. (2021)</xref>
</td>
</tr>
<tr>
<td align="center">Coptis chinensis (Huang Lian)</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx7.tif"/>
<italic>Coptis chinensis</italic> Franch Rhizoma</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx8.tif"/>Berberine</td>
<td align="center">Dispel pathogenic fire Remove dampness<break/>Neutralize toxins</td>
<td align="center">Antibacterial<break/>Anti-inflammatory</td>
<td align="center">NF-&#x3ba;B<break/>S100B/caspase-8/<break/>&#x3b2;-catenin</td>
<td align="center">&#x2193;TNF-&#x3b1;/IL-23<break/>&#x2193;neutrophil aggregation<break/>Enhance granulation tissue<break/>Inhibit M1 macrophages</td>
<td align="center">
<xref ref-type="bibr" rid="B28">Habtemariam (2020)</xref>, <xref ref-type="bibr" rid="B22">Feng et al. (2024)</xref>, <xref ref-type="bibr" rid="B96">Wang S. et al. (2024)</xref>
</td>
</tr>
<tr>
<td align="center">Phellodendron amurense (Huang Bo)</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx9.tif"/>
<italic>Phellodendron chinense</italic> Schneid. Bark</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx10.tif"/>Phellamurin<break/>Berberine</td>
<td align="center">Clearing internal heat<break/>Removing dampness<break/>Reducing pathogenic fire<break/>Detoxification</td>
<td align="center">Immunomodulation Antimicrobial</td>
<td align="center">INF-&#x3b3;<break/>IL-1<break/>TNF-&#x3b1;<break/>IL-2</td>
<td align="center">&#x2193;Pro-inflammatory cytokines<break/>Scavenges free radicals Enhances phagocytosis</td>
<td align="center">
<xref ref-type="bibr" rid="B102">Xian et al. (2011)</xref>, <xref ref-type="bibr" rid="B48">Liu et al. (2022)</xref>
</td>
</tr>
<tr>
<td align="center">Sanguisorba officinalis (Di Yu)</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx11.tif"/>
<italic>Sanguisorba officinalis</italic> L. Rhizoma</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx12.tif"/>Quercetin<break/>Tannins Polysaccharides</td>
<td align="center">Cool blood for hemostasis<break/>Polysaccharides<break/> Clear heat and remove toxins<break/> Reduce swelling Promote ulcer healing.</td>
<td align="center">Antibacterial<break/>Anti-inflammatory</td>
<td align="center">NF-&#x3ba;B/NLRP3<break/>VEGF<break/>IL-1&#x3b2;</td>
<td align="center">&#x2193;<italic>S. aureus</italic>/<italic>P. aeruginosa</italic>
<break/>&#x2191;collagen/angiogenesis Promotes M2 macrophage polarization</td>
<td align="center">
<xref ref-type="bibr" rid="B115">Zhang et al. (2018)</xref>, <xref ref-type="bibr" rid="B81">Song et al. (2023)</xref>
</td>
</tr>
<tr>
<td align="center">Angelica dahurica (Bai Zhi)</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx13.tif"/>
<italic>Angelica dahurica (</italic>Fisch.ex Hoffm.)Benth. et Hook.f. Rhizoma</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx14.tif"/>Imperatorin<break/>Isorhamnetin</td>
<td align="center">Dispel pathogenic wind<break/>Eliminate dampness<break/>Subside swelling<break/>Relieve pain</td>
<td align="center">Antibacterial<break/>Angiogenesis<break/>Anti-inflammatory</td>
<td align="center">HIF-1&#x3b1;/PDGF-&#x3b2;<break/>ERK1/2/Akt/eNOS</td>
<td align="center">Modulates M1/M2 macrophages<break/>&#x2191;NO production</td>
<td align="center">
<xref ref-type="bibr" rid="B114">Zhang et al. (2017)</xref>, <xref ref-type="bibr" rid="B27">Guo et al. (2020)</xref>, <xref ref-type="bibr" rid="B109">Yang et al. (2020)</xref>, <xref ref-type="bibr" rid="B34">Hu et al. (2021)</xref>
</td>
</tr>
<tr>
<td align="center">Natural Borneol (Long Nao)</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx15.tif"/>
<italic>Dryobalanops aromatica</italic> C.F.Gaertn.<break/>Natural crystalline</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx16.tif"/>Borneol</td>
<td align="center">Revives consciousness<break/>Reduces fever and pain<break/>Enhances vision and clears eye opacity</td>
<td align="center">Antioxidant<break/>Anti-inflammatory<break/>Enhance collagen density</td>
<td align="center">HIF-1&#x3b1;/NF-&#x3ba;B</td>
<td align="center">&#x2193;IL-1&#x3b2;/IL-6/TNF-&#x3b1;</td>
<td align="center">
<xref ref-type="bibr" rid="B4">Barreto et al. (2016)</xref>, <xref ref-type="bibr" rid="B52">Lv et al. (2022)</xref>, <xref ref-type="bibr" rid="B12">Chen et al. (2024)</xref>
</td>
</tr>
<tr>
<td align="center">Frankincense (Ru Xiang)</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx17.tif"/>
<italic>Boswellia carterii</italic> Birdw. Resin</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx18.tif"/>Boswellic acid</td>
<td align="center">Regulate qi and promote blood circulation<break/>Relieve pain<break/>Eliminate toxins</td>
<td align="center">Anti-inflammatory<break/>Tissue regeneration</td>
<td align="center">&#x3b2;-catenin<break/>Dlk1<break/>COX-2</td>
<td align="center">&#x2193;Oxidative stress<break/>&#x2193;Apoptosis<break/>&#x2191;collagen/angiogenesis<break/>&#x2191;Growth factors</td>
<td align="center">
<xref ref-type="bibr" rid="B65">Pengzong et al. (2019)</xref>, <xref ref-type="bibr" rid="B110">Yin et al. (2022)</xref>
</td>
</tr>
<tr>
<td align="center">Myrrh (Mo Yao)</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx19.tif"/>
<italic>Commiphora myrrha</italic>
<break/> (T.Nees) Engl. <break/>Resin</td>
<td align="center">
<inline-graphic xlink:href="fphar-16-1651219-fx20.tif"/>Bisacurone</td>
<td align="center">Disperse and eliminate blood stasis Subside swelling Relieve pain</td>
<td align="center">Angiogenesis<break/>Anti-inflammatory</td>
<td align="center">Oxidative stress markers pro-inflammatory cytokines</td>
<td align="center">&#x2193;Inflammatory response<break/>&#x2191;granulation tissue</td>
<td align="center">
<xref ref-type="bibr" rid="B128">Soliman et al. (2019)</xref>, <xref ref-type="bibr" rid="B5">Batiha et al. (2023)</xref>, <xref ref-type="bibr" rid="B107">Yan et al. (2023)</xref>
</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
</sec>
<sec id="s2">
<title>Radix arnebiae</title>
<p>Radix Arnebiae (Zi Cao), derived from the dried roots of <italic>Arnebia euchroma</italic> (Royle) Johnst. or <italic>Arnebia guttata</italic> Bunge as specified in the Chinese Pharmacopoeia, is widely used in TCM to clear heat, cool blood, promote circulation, detoxify, and eliminate rashes (<xref ref-type="bibr" rid="B112">Zhan et al., 2015</xref>). Clinically, it is often combined with herbs such as <italic>Phellodendron amurense</italic> Rupr.<italic>, Saposhnikovia divaricata</italic> (Turcz. ex Ledeb.) Schischk.<italic>, Angelica dahurica</italic> (Hoffm.) Benth. &#x26; Hook.f.<italic>, Angelica sinensis</italic> (Oliv.) Diels, and borneol to accelerate wound healing and reduce treatment time for burns (<xref ref-type="bibr" rid="B26">Guo et al., 2019</xref>). Radix arnebiae oil (RAO), a common TCM formulation, has shown significant therapeutic efficacy in burn treatment. In a rat burn model, topical application of RAO at a dose of 0.3&#xa0;g twice daily was initiated on day 1 post-burn. This treatment regimen significantly enhanced superoxide dismutase activity, reduces malondialdehyde production, downregulates pro-inflammatory cytokines (IL-6, IL-1&#x3b2;, and TNF-&#x3b1;), and promotes the secretion of growth factors (VEGF, EGF, and TGF-&#x3b2;), thereby accelerating epithelial regeneration and scar repair. Its mechanism may involve activation of the TGF-&#x3b2;1/PI3K/Akt pathway (<xref ref-type="bibr" rid="B24">Gao et al., 2023</xref>).</p>
<p>Shikonin (SNK), the principal active component of Arnebia euchroma (Royle) Johnst., exhibits anti-inflammatory, antibacterial, and wound-healing properties. SNK suppresses inflammation by inhibiting the NF-&#x3ba;B signaling pathway, reducing the expression of Bax, p-p65, and p-p38, while upregulating Bcl-2. It also activates the Wnt signaling pathway through the upregulation of Wnt4, promoting cell proliferation and epithelial tissue regeneration (<xref ref-type="bibr" rid="B84">Sun et al., 2022</xref>). Topical SNK ointment enhances wound healing by activating the PI3K/Akt pathway and protecting deep hair follicles (<xref ref-type="bibr" rid="B101">Wu T. et al., 2022</xref>).</p>
<p>Hypertrophic scar formation remains a significant clinical challenge post-burn. SNK regulates the AMPK/mTOR signaling pathway, promoting autophagy and apoptosis in hypertrophic scar-derived fibroblasts (HSFs) (<xref ref-type="bibr" rid="B103">Xie et al., 2015</xref>; <xref ref-type="bibr" rid="B116">Zhang et al., 2023</xref>). Animal studies demonstrate that sprayed 1&#xa0;mL of 1.0&#xa0;&#x3bc;g/mL SNK onto the surface of hypertrophic scars every 2&#xa0;days improves scar repair. This improvement is mediated by the suppression of p63, keratin 10, &#x3b1;-smooth muscle actin, TGF-&#x3b2;, and type I collagen (<xref ref-type="bibr" rid="B16">Deng et al., 2018</xref>). A recent innovation involves a temperature-sensitive hydrogel composed of chitosan-&#x3b2;-glycerophosphate, mesoporous carbon nanospheres, nitric oxide (NO) donor sodium nitroprusside, and SNK (loaded at 800&#xa0;&#x3bc;g/mL). This hydrogel exhibits broad-spectrum antibacterial activity, releases NO under near-infrared (NIR) laser irradiation to promote angiogenesis, inhibits fibroblast overproliferation, and effectively reduces scars in deep second-degree burns, highlighting its potential as a novel clinical product for scar treatment (<xref ref-type="bibr" rid="B3">Bai et al., 2024</xref>).</p>
<p>Burn wounds are prone to bacterial infections, including methicillin-resistant <italic>Staphylococcus aureus</italic> (MRSA), which often form drug-resistant biofilms. SNK-liposomes (SNK concentration 4.6% &#xb1; 0.17%), prepared using a film formation method, exhibit sustained release and strong antibacterial activity by disrupting bacterial cell walls and membranes. These liposomes modulate the I&#x3ba;B&#x3b1;/NF&#x3ba;B-p65 signaling pathway, alleviating inflammation and promoting healing in MRSA-infected burn wounds (<xref ref-type="bibr" rid="B79">Shu et al., 2022</xref>). Additionally, bio-adhesive nanoparticles (BNP) based on polylactic acid-hyperbranched polyglycerol (PLA-HPG) enhance SNK&#x2019;s (loaded at 3.6% &#xb1; 0.1%) anti-biofilm and wound-healing properties, making SNK/BNP a promising treatment for infected burn wounds (<xref ref-type="bibr" rid="B31">Han et al., 2023</xref>).</p>
<sec id="s2-1">
<title>Rhubarb</title>
<p>Rhubarb (Da Huang), the dried rhizome and root of <italic>Rheum palmatum</italic> L. is widely used in TCM to eliminate heat-toxins, clear accumulations, promote blood circulation, and facilitate tissue regeneration. Standardized extracts (typically containing 2%&#x2013;4% total anthraquinones) is frequently employed in burn treatment. Animal studies demonstrate that rhubarb extract (administered at 50&#xa0;mg/kg/day) enhances the activity of cytochrome oxidase and superoxide dismutase (SOD) in intestinal mucosal epithelial cells of burned rats, reducing mitochondrial oxygen free radical leakage. It also decreases immunoglobulin A (IgA) content in intestinal fluid and alleviates trauma or burn-induced intestinal mucosal damage (<xref ref-type="bibr" rid="B8">Chen et al., 2000</xref>). A clinical trial involving 30 severely burned patients revealed that rhubarb (at 30g/day) increases gastrointestinal hormone secretion, restores gastrointestinal motility, and protects the intestinal mucosal barrier (<xref ref-type="bibr" rid="B57">Meng et al., 2011</xref>). Furthermore, rhubarb (at 50&#xa0;mg/kg) mitigates antibiotic-induced dysbiosis by reducing the bactericidal effect on symbiotic bacteria in early sepsis and exerts anti-inflammatory and immune-regulating effects during burn-induced sepsis (<xref ref-type="bibr" rid="B9">Chen et al., 2009</xref>; <xref ref-type="bibr" rid="B47">Liu et al., 2019</xref>). Recent studies highlight a scaffold composed of cross-linked chitosan and rhubarb-derived charcoal (RCS/SF), which exhibits rapid hemostasis, antibacterial activity, and efficient drug release (rhubarb extract loaded at 20 or 100&#xa0;mg). This scaffold promotes diabetic wound healing in db/db mice by enhancing neovascularization, collagen deposition, and re-epithelialization within 2&#xa0;weeks. Additionally, it modulates the AMPK signaling pathway, reducing hepatic lipid accumulation, inflammation, and oxidative stress, underscoring its systemic regulatory role (<xref ref-type="bibr" rid="B94">Wang et al., 2023</xref>; <xref ref-type="bibr" rid="B86">Tan et al., 2024</xref>).</p>
<p>Emodin, a primary active compound in rhubarb (standardized to &#x3e;90% purity), enhances fibroblast fibrinolytic activity and migration at concentrations of 30 or 50&#xa0;&#x3bc;M, facilitating wound healing (<xref ref-type="bibr" rid="B70">Radha et al., 2008</xref>). It also promotes type I collagen synthesis in dermal fibroblasts at 1&#xa0;&#x3bc;M (<xref ref-type="bibr" rid="B80">Song et al., 2021</xref>). In animal studies, emodin (applied at (400&#xa0;&#x3bc;g/mL) accelerates excisional wound healing by stimulating epidermal cell proliferation, capillary generation, and microcirculation, while reducing inflammation via inhibition of the TLR4/NF-&#x3ba;B signaling pathway (<xref ref-type="bibr" rid="B87">Tang et al., 2007</xref>). Emodin also alleviates hypertrophic scar formation by inhibiting macrophage polarization (at 10&#x2013;40&#xa0;&#x3bc;M), potentially through suppression of the Notch and TGF-&#x3b2; pathways (<xref ref-type="bibr" rid="B74">S&#xe1;nchez et al., 2020</xref>). Additionally, emodin shows therapeutic potential for corneal alkali burns (at 10&#x2013;20&#xa0;&#x3bc;M) by suppressing inflammatory cell infiltration and angiogenesis (<xref ref-type="bibr" rid="B38">Kitano et al., 2007</xref>; <xref ref-type="bibr" rid="B106">Xueying et al., 2024</xref>). To address bacterial infections, a critical factor in wound healing, nano-emodin (N-EMO)-mediated photodynamic therapy (at 40&#xa0;&#x3bc;g/mL) effectively targets multi-species bacterial biofilms, reducing biofilm formation and virulence factors (<xref ref-type="bibr" rid="B66">Pourhajibagher et al., 2021</xref>). A recent study developed a double-network hydrogel incorporating emodin (at a concentration of 0.03%) and chitosan, which significantly promotes blood vessel and collagen regeneration, accelerating wound healing in animal models (<xref ref-type="bibr" rid="B92">Wan et al., 2023</xref>).</p>
</sec>
<sec id="s2-2">
<title>Angelica sinensis</title>
<p>Angelica sinensis, the dried root of <italic>Angelica sinensis</italic> (Oliv.) Diels (known as Dang Gui), is widely used in TCM to promote blood circulation, regulate menstruation, alleviate pain, and relieve constipation (<xref ref-type="bibr" rid="B60">Nai et al., 2021</xref>). Standardized extracts (often containing ligustilide &#x3e;0.5%) are clinically employed to treat various skin wounds and accelerate wound healing. Research has shown that Angelica sinensis extract (at 100&#xa0;&#x3bc;g/mL) promotes the proliferation of human umbilical vein endothelial cells (HUVECs) by modulating the phosphorylation of p38 and JNK 1/2, upregulating VEGF expression, and facilitating angiogenesis (<xref ref-type="bibr" rid="B42">Lam et al., 2008</xref>). Additionally, it enhances the proliferation of human dermal fibroblasts and the production of type I collagen, significantly accelerating wound healing in mice (topical application of 2% gel) (<xref ref-type="bibr" rid="B118">Zhao et al., 2012</xref>).</p>
<p>The main bioactive constituents of <italic>Angelica sinensis</italic> (Oliv.) Diels include Angelica sinensis polysaccharides, ligustilide, and ferulic acid (FA). FA (typically used at 10&#x2013;100&#xa0;&#x3bc;M <italic>in vitro</italic> or 5&#x2013;100&#xa0;mg/kg <italic>in vivo</italic>), in particular, exhibits multifunctional properties such as anti-inflammatory, antibacterial, collagen-promoting, angiogenic, and re-epithelialization effects, making it a promising candidate for burn-related wound healing (<xref ref-type="bibr" rid="B44">Li et al., 2021</xref>). Yuhong Ointment (YHO), a traditional formulation used for over 600 years to treat skin diseases, contains active constituents such as FA, L-hydroxyproline, chlorogenic acid, and sermanine. These components exert anti-inflammatory and tissue-regenerative effects, demonstrating significant therapeutic efficacy in burns and scalds (<xref ref-type="bibr" rid="B111">Yu et al., 2023</xref>).</p>
<p>A recent study developed a biodegradable, multifunctional spray hydrogel containing FA (at 1.0&#xa0;wt%), which significantly enhances fibroblast proliferation, accelerates infected wound healing, and prevents secondary injuries, highlighting its potential for clinical application (<xref ref-type="bibr" rid="B123">Zhong et al., 2024</xref>). In a rabbit corneal alkali burn model, a thermosensitive chitosan-based hydrogel containing FA (1&#xa0;mg/mL) significantly reduced inflammatory factors and suppressed cell apoptosis, promoting corneal wound healing (<xref ref-type="bibr" rid="B90">Tsai et al., 2016</xref>). Furthermore, a multifunctional hydrogel containing FA (at 2% (w/v)) has been shown to inhibit MRSA infection, reduce excessive inflammation, promote angiogenesis, and accelerate wound healing and skin tissue regeneration (<xref ref-type="bibr" rid="B45">Li et al., 2024</xref>). A nano-hydrogel composed of FA-grafted chitosan exhibits enhanced antioxidant activity by scavenging ABTS and DPPH free radicals, while effectively inhibiting <italic>Bacillus subtilis</italic>, MRSA, <italic>Escherichia coli</italic>, and <italic>Pseudomonas aeruginosa</italic>, facilitating the healing of infected wounds (<xref ref-type="bibr" rid="B67">Prasathkumar et al., 2024</xref>).</p>
</sec>
<sec id="s2-3">
<title>Coptis chinensis</title>
<p>Coptis chinensis (Huang Lian), the dried <italic>rhizome of Coptis chinensis</italic> Franch., is widely used in TCM to clear heat and dampness, purge fire, and detoxify (<xref ref-type="bibr" rid="B93">Wang et al., 2019</xref>). Its standardized extracts, which typically contain total alkaloids &#x3e;10% (including berberine &#x3e;5%), are commonly incorporated into modern formulations. Huang Lian Jie Du Decoction, a classic TCM formula, exhibits anti-inflammatory, antibacterial, and microcirculation-improving effects, making it effective for treating burns and febrile diseases (<xref ref-type="bibr" rid="B68">Qi et al., 2019</xref>). Berberine (BBR), the main active ingredient of <italic>Coptis chinensis</italic> Franch. (standardized to &#x3e;97% purity), demonstrates potent antibacterial and anti-inflammatory properties (<xref ref-type="bibr" rid="B39">Kong et al., 2022</xref>). BBR inhibits the secretion of pro-inflammatory cytokines (e.g., TNF-&#x3b1; and IL-23) by suppressing NF-&#x3ba;B activity, modulating neutrophil migration, and reducing neutrophil aggregation in inflammatory regions, thereby mitigating inflammatory responses (<xref ref-type="bibr" rid="B28">Habtemariam, 2020</xref>). Recent studies indicate that BBR (at 100&#xa0;mg/kg/d) reduces burn-induced gut vascular barrier hyperpermeability by modulating the S100B/caspase-8/&#x3b2;-catenin pathway, potentially involving enteric glial cells (<xref ref-type="bibr" rid="B22">Feng et al., 2024</xref>).</p>
<p>To address antibiotic resistance, Sun S. et al. developed an antibiotic-free polysaccharide-based hydrogel dressing (ATB) containing BBR hydrochloride (loaded at 1&#xa0;mg/mL). This dressing synergistically eliminates bacteria and accelerates wound healing in both <italic>in vitro</italic> and <italic>in vivo</italic> experiments, offering a solution to the overuse of antibiotics (<xref ref-type="bibr" rid="B85">Sun et al., 2024</xref>). Additionally, silk fibroin microspheres loaded with berberine (Ber@MPs, BBR loading 40&#xa0;mg) exhibit strong antibacterial effects against <italic>Staphylococcus aureus</italic> and <italic>Staphylococcus epidermidis</italic>, reduce inflammation, promote fibroblast migration and endothelial cell neovascularization, and significantly accelerate infected wound healing (<xref ref-type="bibr" rid="B75">Sang et al., 2023</xref>; <xref ref-type="bibr" rid="B117">Zhang et al., 2024</xref>).</p>
<p>Wound healing, a complex biological process critical for tissue repair, is enhanced by BBR-containing cryogels (loading at 2.08%&#x2013;5.88%), which accelerate granulation tissue formation, epithelial regeneration, and collagen deposition (<xref ref-type="bibr" rid="B15">Dar et al., 2024</xref>). Furthermore, nanofiber dressing patches containing BBR (loading at 4.82%&#x2013;13.69%) inhibit pro-inflammatory factor secretion by M1 macrophages, promote fibroblast proliferation, and exhibit broad-spectrum antimicrobial activity. Animal studies demonstrate that these dressings (applied at 1&#x2013;2&#xa0;mg/cm<sup>2</sup>) accelerate full-thickness skin wound healing, shorten healing time, and improve healing quality, highlighting their potential for treating chronic and difficult-to-heal wounds (<xref ref-type="bibr" rid="B95">Wang Q. et al., 2024</xref>).</p>
</sec>
<sec id="s2-4">
<title>Phellodendron amurense</title>
<p>Phellodendri Cortex (Huang Bo), the dried bark of <italic>Phellodendron chinense</italic> Schneid. or <italic>Phellodendron amurense</italic> Rupr. as specified in the Chinese Pharmacopoeia, is widely used in TCM to clear heat, remove dampness, purge fire, and detoxify (<xref ref-type="bibr" rid="B83">Sun et al., 2019</xref>). Standardized extracts (typically containing berberine &#x3e;3%, total alkaloids &#x3e;5%) are commonly used. Research demonstrates that <italic>Phellodendron chinense Schneid.</italic> extract (at 100&#x2013;500&#xa0;mg) exerts immunomodulatory effects by inhibiting the production and secretion of key cytokines such as interferon-&#x3b3; (INF-&#x3b3;), IL-1, TNF-&#x3b1;, and IL-2, thereby alleviating inflammatory damage (<xref ref-type="bibr" rid="B102">Xian et al., 2011</xref>). It also exhibits antioxidant effects by scavenging free radicals and enhances the phagocytic function of monocytes/macrophages, improving nonspecific immunity (<xref ref-type="bibr" rid="B48">Liu et al., 2022</xref>). The main bioactive constituents, including phellodendri, berberine, and other alkaloids, display significant antimicrobial activity against pathogens such as <italic>Staphylococcus aureus</italic>, <italic>Streptococcus albus</italic>, <italic>Streptococcus pneumoniae</italic>, <italic>Bacillus subtilis</italic>, and <italic>Pseudomonas aeruginosa</italic> (<xref ref-type="bibr" rid="B10">Chen et al., 2010</xref>).</p>
</sec>
<sec id="s2-5">
<title>Sanguisorba officinalis</title>
<p>Sanguisorba officinalis (Di Yu), the dried rhizome of <italic>Sanguisorba officinalis</italic> L., is widely used in TCM to cool blood, stop bleeding, clear heat, detoxify, reduce swelling, and promote wound healing. Standardized extracts (often containing tannins &#x3e;10%, total flavonoids &#x3e;2%) are typically employed. Modern research has identified a rich variety of bioactive compounds in Sanguisorba officinalis, including tannins, triterpenoids, flavonoids, and polysaccharides. Pharmacological studies have demonstrated its diverse functions, such as hemostatic, antibacterial, anti-tumor, anti-allergic, anti-inflammatory, and anti-edema effects (<xref ref-type="bibr" rid="B124">Zhou et al., 2021</xref>). The antibacterial activity of <italic>Sanguisorba officinalis</italic> L. is primarily attributed to its tannin components, which exhibit inhibitory effects against pathogens such as <italic>Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and Streptococcus pneumoniae</italic> (<xref ref-type="bibr" rid="B119">Zhao et al., 2017</xref>). Quercetin, a flavonoid present in <italic>Sanguisorba officinalis</italic>, has been identified as a key contributor to its antioxidant effects, which are beneficial for promoting wound healing (<xref ref-type="bibr" rid="B35">Jang et al., 2018</xref>). Additionally, the ethanol extract of <italic>Sanguisorba officinalis</italic> extracts (at 2.5&#x2013;10&#xa0;g/kg/d) accelerates diabetic wound healing by inhibiting the NF-&#x3ba;B/NLRP3 signaling pathway and facilitating macrophage polarization from the M1 to the M2 phenotype (<xref ref-type="bibr" rid="B81">Song et al., 2023</xref>). A purified polysaccharide (SOP) extracted from <italic>Sanguisorba officinalis</italic> L. has shown remarkable efficacy in mouse burn models, significantly accelerating wound contraction and reducing epithelialization time. SOP administration increases levels of IL-1&#x3b2; and VEGF, promoting granulation tissue formation, collagen synthesis, and angiogenesis, thereby expediting wound repair (<xref ref-type="bibr" rid="B115">Zhang et al., 2018</xref>).</p>
</sec>
<sec id="s2-6">
<title>Angelica dahurica</title>
<p>Angelica dahurica (Bai Zhi), the dried root of <italic>Angelica dahurica</italic> (Fisch. ex Hoffm.) Benth. &#x26; Hook.f., is traditionally used in TCM to dispel wind, eliminate dampness, reduce swelling, and relieve pain. Standardized extracts (typically containing imperatorin &#x3e;0.5%, total coumarins &#x3e;2%) are used. Modern pharmacological studies reveal its anti-inflammatory, analgesic, antispasmodic, and antibacterial properties (<xref ref-type="bibr" rid="B120">Zhao et al., 2022</xref>). Animal experiments demonstrate that <italic>Angelica dahurica</italic> (Fisch. ex Hoffm.) Benth. &#x26; Hook.f. water extract (at 6g//kg/d) modulates macrophage polarization (M1/M2), exerting anti-inflammatory effects and promoting wound healing (<xref ref-type="bibr" rid="B34">Hu et al., 2021</xref>). Its combination with <italic>Angelica sinensis</italic> (Oliv.) Diels and <italic>Rheum officinale Baill.</italic> enhances wound healing during inflammatory and proliferative phases (<xref ref-type="bibr" rid="B108">Yang et al., 2017</xref>; <xref ref-type="bibr" rid="B7">Chao et al., 2021</xref>). Additionally, <italic>Angelica dahurica</italic> (Fisch. ex Hoffm.) Benth. &#x26; Hook.f. promotes angiogenesis in HUVECs by upregulating the HIF-1&#x3b1;/PDGF-&#x3b2; pathway and enhancing angiogenic signals such as ERK1/2, Akt, eNOS, and NO production, suggesting its potential for vascular injury-related wounds (<xref ref-type="bibr" rid="B114">Zhang et al., 2017</xref>; <xref ref-type="bibr" rid="B27">Guo et al., 2020</xref>). Key bioactive compounds include imperatorin, isoimperatorin, and psoralen. Recent studies highlight isorhamnetin (applied at 0.1%&#x2013;0.5% topically), which alleviates chronic inflammation, promotes epithelial regeneration, and accelerates <italic>Staphylococcus aureus</italic> infected wound healing through its anti-inflammatory, proliferative, and antibacterial properties (<xref ref-type="bibr" rid="B109">Yang et al., 2020</xref>; <xref ref-type="bibr" rid="B41">Lakshmanan et al., 2024</xref>).</p>
</sec>
<sec id="s2-7">
<title>Natural borneol</title>
<p>Natural borneol, which is derived from the tree <italic>Dryobalanops aromatica</italic> C.F.Gaertn. and standardized to a purity of &#x3e;96%, is used in TCM for opening the orifices, improving mental alertness, clearing heat, and relieving pain. Research shows that borneol promotes wound healing by mitigating oxidative stress, facilitating neutrophil recruitment, and suppressing inflammatory cytokines (IL-1&#x3b2;, IL-6, and TNF-&#x3b1;) via inhibition of the HIF-1&#x3b1;/NF-&#x3ba;B pathway (<xref ref-type="bibr" rid="B12">Chen et al., 2024</xref>). A chitosan-based film containing 1% borneol (QUIBO1) accelerates wound contraction, enhances granulation tissue formation, and improves collagen density (<xref ref-type="bibr" rid="B4">Barreto et al., 2016</xref>). Nanofibers incorporating alum and borneol, fabricated via coaxial electrospinning, increase borneol dissolution and wound healing efficacy (<xref ref-type="bibr" rid="B52">Lv et al., 2022</xref>). Additionally, a natural antibacterial hydrogel, synthesized through Schiff base cross-linking of carboxymethyl chitosan and dialdehyde dextran grafted with borneol, exhibits strong antibacterial activity against <italic>Escherichia coli</italic> and <italic>Staphylococcus aureus</italic>, excellent cytocompatibility, and targeted delivery potential for localized wound infections (<xref ref-type="bibr" rid="B121">Zhao et al., 2024</xref>).</p>
</sec>
<sec id="s2-8">
<title>Frankincense</title>
<p>Frankincense (Chinese name: Ru Xiang), the resin obtained from <italic>Boswellia sacra</italic> Fl&#xfc;ck<italic>.</italic> and related species and standardized to contain boswellic acids (&#x3e;30%), is traditionally used in TCM to promote blood circulation, alleviate pain, and eliminate toxins. Its bioactive constituents, primarily pentacyclic triterpenes (e.g., boswellic acids) and volatile oils, have been demonstrated to possess anti-inflammatory, anti-proliferative, analgesic, antioxidant, and antibacterial properties (<xref ref-type="bibr" rid="B58">Morikawa et al., 2017</xref>). Boswellic acids (effective at 5&#x2013;50&#xa0;&#x3bc;M) promote wound healing by inhibiting oxidative inflammatory markers, enhancing collagen synthesis and angiogenesis, promoting growth factors, and suppressing apoptosis (<xref ref-type="bibr" rid="B65">Pengzong et al., 2019</xref>). Clinical studies confirm the efficacy of myrrh and frankincense-based sitz baths in post-episiotomy wound healing (<xref ref-type="bibr" rid="B20">Faraji et al., 2021</xref>). Incorporating essential oils (e.g., clove, cinnamon, frankincense) into biodegradable polymer membranes enhances biological activity and protects against degradation, offering a novel approach to wound healing dressings (<xref ref-type="bibr" rid="B6">Borges et al., 2024</xref>). ShengFu Oil, a topical TCM formulation, contains standardized extracts of <italic>Scutellaria baicalensis</italic> Georgi, <italic>Boswellia carterii</italic> Birdw., and <italic>Rheum palmatum</italic> L. It has been demonstrated to possess anti-inflammatory, analgesic, and antibacterial properties. It facilitates burn wound healing through the regulation of key biomarkers (&#x3b2;-catenin, Dlk1, COX-2) and concurrent modulation of the inflammatory microenvironment, playing a vital role in the prevention and treatment of oral chemical burns (<xref ref-type="bibr" rid="B30">Han et al., 2017</xref>; <xref ref-type="bibr" rid="B110">Yin et al., 2022</xref>).</p>
</sec>
<sec id="s2-9">
<title>Myrrh</title>
<p>Myrrh (Chinese name: Mo Yao), the resin obtained from <italic>Commiphora</italic> myrrha (T.Nees) Engl. and standardized to contain volatile oils (&#x3e;5%), is traditionally used in TCM to disperse blood stasis, alleviate pain, reduce swelling, and promote tissue regeneration.</p>
<p>The therapeutic efficacy and indications of myrrh are highly similar to those of frankincense, often resulting in their combined application in clinical practice. Research results have shown that the topical application of perilla-frankincense-myrrh volatile oil can attenuate the inflammatory response in the early stage of wounds and expedite wound healing in mice (<xref ref-type="bibr" rid="B5">Batiha et al., 2023</xref>). Jinchuang ointment, a TCM compound composed of borneol, catechu, frankincense, and myrrh, displays the functions of promoting angiogenesis, cell proliferation, and migration activity, which is conducive to the enhancement of the wound healing process (<xref ref-type="bibr" rid="B33">Ho et al., 2016</xref>). Bisacurone is one of the main bioactive compounds in myrrh. Recent research has demonstrated that the topical application of bisacurone gel (0.5%&#x2013;2% concentration) can effectively diminish oxidative stress and pro-inflammatory cytokines, promote angiogenesis and granulation tissue formation, and remarkably accelerate the healing of wounds in second-degree burn rats (<xref ref-type="bibr" rid="B107">Yan et al., 2023</xref>).</p>
</sec>
</sec>
<sec id="s3">
<title>Treatment of burn with TCM preparations</title>
<p>TCM external treatments are a cornerstone of burn management, offering remarkable therapeutic efficacy with minimal side effects. With advancements in modern TCM pharmacology, a variety of external preparations, such as ointments, sprays, powders, tinctures, hydrogels, and nanofibers, have been developed and widely used in clinical practice. These formulations, combined with innovations in biomaterials and tissue engineering, provide effective solutions for wound management. This review systematically summarizes the application of TCM preparations in burn treatment, with a focus on their active ingredients, therapeutic effects and mechanisms (<xref ref-type="table" rid="T2">Table 2</xref>).</p>
<table-wrap id="T2" position="float">
<label>TABLE 2</label>
<caption>
<p>TCM preparations for burn treatment.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="center">Herbs/Active ingredients</th>
<th align="center">Dosage form</th>
<th align="center">Preparations</th>
<th align="center">Therapeutic effects</th>
<th align="center">Mechanism</th>
<th align="center">References</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="center">Radix arnebiae Shikonin (SNK)</td>
<td align="center">Oil<break/>Spray<break/>Ointment<break/>Hydrogel<break/>Liposome<break/>Nanoparticle</td>
<td align="center">Radix arnebiae oil (RAO)<break/>Radix arnebiae spray<break/>Shikonin (SNK) ointment<break/>Temperature-sensitive hydrogel<break/>SNK-liposomes<break/>SNK/BNP nanoparticles</td>
<td align="center">Anti-inflammatory<break/>Antibacterial<break/>Promotes epithelial regeneration<break/>Promotes angiogenesis<break/>Wound healing<break/>Scar reduction</td>
<td align="center">Inhibit NF-&#x3ba;B<break/>Activate Wnt/PI3K/Akt<break/>Modulate TGF-&#x3b2;1/PI3K/Akt<break/>AMPK/mTOR pathways</td>
<td align="center">
<xref ref-type="bibr" rid="B79">Shu et al. (2022)</xref>, <xref ref-type="bibr" rid="B101">Wu T. et al. (2022)</xref>, <xref ref-type="bibr" rid="B31">Han et al. (2023)</xref>, <xref ref-type="bibr" rid="B50">Liu et al. (2024)</xref>
</td>
</tr>
<tr>
<td align="center">Rhubarb<break/>Emodin<break/>Rhubarb-derived charcoal</td>
<td align="center">Scaffold<break/>Biofilm<break/>Hydrogel</td>
<td align="center">Rhubarb charcoal-crosslinked chitosan/silk fibroin sponge scaffold<break/>Nano-emodin (N-EMO) biofilms<break/>Chitosan-emodin network hydrogel</td>
<td align="center">Antioxidant<break/>Anti-inflammatory<break/>Promote tissue regeneration<break/>Wound healing</td>
<td align="center">Enhance SOD activity<break/>Inhibit TLR4/NF-&#x3ba;B<break/>Modulate AMPK pathway</td>
<td align="center">
<xref ref-type="bibr" rid="B66">Pourhajibagher et al. (2021)</xref>, <xref ref-type="bibr" rid="B92">Wan et al. (2023)</xref>, <xref ref-type="bibr" rid="B94">Wang et al. (2023)</xref>, <xref ref-type="bibr" rid="B86">Tan et al. (2024)</xref>
</td>
</tr>
<tr>
<td align="center">Angelica sinensis<break/>Ferulic acid (FA)<break/>Angelica polysaccharides<break/>Ligustilide</td>
<td align="center">Ointment<break/>Hydrogel</td>
<td align="center">Yuhong Ointment (YHO)<break/>CSMA-FA/OBSP (CSOB-FA) hydrogel<break/>Thermosensitive chitosan-FA hydrogel<break/>Bioactive poly(FA) hydroge<break/>FA-grafted chitosan nano-hydrogel</td>
<td align="center">Angiogenesis<break/>Collagen synthesis<break/>Anti-inflammatory<break/>Anti-scarring</td>
<td align="center">Upregulate VEGF<break/>Modulate p38/JNK pathways<break/>Promote fibroblast proliferation</td>
<td align="center">
<xref ref-type="bibr" rid="B90">Tsai et al. (2016)</xref>, <xref ref-type="bibr" rid="B111">Yu et al. (2023)</xref>, <xref ref-type="bibr" rid="B45">Li et al. (2024)</xref>, <xref ref-type="bibr" rid="B67">Prasathkumar et al. (2024)</xref>, <xref ref-type="bibr" rid="B123">Zhong et al. (2024)</xref>
</td>
</tr>
<tr>
<td align="center">Coptis chinensis<break/>Berberine (BBR)</td>
<td align="center">Decoction<break/>Hydrogel<break/>Cryogel<break/>Microsphere<break/>Nanofiber</td>
<td align="center">Huang Lian Jie Du Decoction<break/>Polysaccharide-based hydrogel with BBR<break/>BBR-containing cryogels<break/>Berberine-loaded silk fibroin microspheres<break/>BBR nanofiber dressing patches</td>
<td align="center">Antibacterial<break/>Anti-inflammatory<break/>Promote fibroblast migration<break/>Enhance neovascularization<break/>Wound healing</td>
<td align="center">Inhibit NF-&#x3ba;B, Modulates S100B/caspase-8/&#x3b2;-catenin<break/>&#x2191;Granulation tissue formation, collagen deposition and<break/>epithelial regeneration</td>
<td align="center">
<xref ref-type="bibr" rid="B68">Qi et al. (2019)</xref>, <xref ref-type="bibr" rid="B75">Sang et al. (2023)</xref>, <xref ref-type="bibr" rid="B15">Dar et al. (2024)</xref>, <xref ref-type="bibr" rid="B85">Sun et al. (2024)</xref>, <xref ref-type="bibr" rid="B95">Wang Q. et al. (2024)</xref>
</td>
</tr>
<tr>
<td align="center">Phellodendron amurense<break/>Coptis chinensis<break/>Scutellaria</td>
<td align="center">Ointment</td>
<td align="center">Moist Exposed Burn Ointment (MEBO)</td>
<td align="center">Antibacterial Analgesi<break/>Promote granulation tissue formation<break/>Activate epidermal stem cells</td>
<td align="center">&#x2191;VEGF/bFGF<break/>Activate PI3K-Akt-mTOR pathway<break/>Induce the autophagy process</td>
<td align="center">
<xref ref-type="bibr" rid="B53">Mabvuure et al. (2020)</xref>, <xref ref-type="bibr" rid="B122">Zheng et al. (2020)</xref>
</td>
</tr>
<tr>
<td align="center">Phellodendron amurense<break/>Coptis chinensis<break/>Rhubarb</td>
<td align="center">Powder</td>
<td align="center">Sanhuang powder</td>
<td align="center">Anti-inflammatory<break/>Heat-clearing<break/>Detoxifying</td>
<td align="center">&#x2193;IL-8/GM-CSF</td>
<td align="center">
<xref ref-type="bibr" rid="B99">Wu et al. (2021)</xref>
</td>
</tr>
<tr>
<td align="center">Phellodendron amurense Cinnabar, Safflower</td>
<td align="center">Tincture</td>
<td align="center">Qi Wei Anti-burn Tincture</td>
<td align="center">Anti-inflammatory<break/>Antioxidant<break/>Liver protection</td>
<td align="center">&#x2191;TGF-&#x03B2;1, FGF-2<break/>&#x2193;TNF-&#x03B1;, IL-1&#x03B2;, IL-6<break/>&#x2193;ROS reduction </td>
<td align="center">(<xref ref-type="bibr" rid="B96">Wang S. et al., 2024b</xref>)</td>
</tr>
<tr>
<td align="center">Borneol</td>
<td align="center">Film<break/>Hydrogel<break/>Nanofiber</td>
<td align="center">Borneol-chitosan film<break/>Schiff base-crosslinked hydrogel<break/>Alum/borneol coaxial nanofibers</td>
<td align="center">Anti-inflammatory<break/>Antibacterial activity<break/>Wound healing</td>
<td align="center">Inhibit HIF-1&#x3b1;/NF-&#x3ba;B<break/>Promote granulation<break/>Improve collagen density</td>
<td align="center">
<xref ref-type="bibr" rid="B4">Barreto et al. (2016)</xref>, <xref ref-type="bibr" rid="B52">Lv et al. (2022)</xref>, <xref ref-type="bibr" rid="B121">Zhao et al. (2024)</xref>
</td>
</tr>
<tr>
<td align="center">Aloe vera, Borneol Musk, Mint</td>
<td align="center">Gel</td>
<td align="center">Aloe vera gel</td>
<td align="center">Reduce itching and pain<break/>Enhance re-epithelialization</td>
<td align="center">Stimulate fibroblast<break/>and keratinocyte proliferation</td>
<td align="center">
<xref ref-type="bibr" rid="B54">Mahboub et al. (2021)</xref>
</td>
</tr>
<tr>
<td align="center">Scutellaria baicalensis<break/>Frankincense, Rhubarb</td>
<td align="center">Oil</td>
<td align="center">ShengFu Oil</td>
<td align="center">Anti-inflammatory<break/>Wound healing</td>
<td align="center">Regulate &#x3b2;-catenin/Dlk1/COX-2</td>
<td align="center">
<xref ref-type="bibr" rid="B110">Yin et al. (2022)</xref>
</td>
</tr>
<tr>
<td align="center">Borneol, Catechu, Frankincense, Myrrh</td>
<td align="center">Ointment</td>
<td align="center">Jinchuang ointment</td>
<td align="center">Stimulate angiogenesis<break/>Promote cell proliferation<break/>Enhance cell migration</td>
<td align="center">Angiogenic activity<break/>Wound healing promotion</td>
<td align="center">
<xref ref-type="bibr" rid="B33">Ho et al. (2016)</xref>
</td>
</tr>
<tr>
<td align="center">Bisacurone</td>
<td align="center">Gel</td>
<td align="center">Chitosan-based bisacurone gel&#xa0;</td>
<td align="center">Anti-inflammatory<break/>Oxidative stress reduction<break/>Enhance angiogenesis</td>
<td align="center">&#x2193;Pro-inflammatory cytokines<break/>&#x2193;MDA, NO; &#x2191;SOD, glutathione<break/>&#x2191;Growth factors</td>
<td align="center">
<xref ref-type="bibr" rid="B107">Yan et al. (2023)</xref>
</td>
</tr>
<tr>
<td align="center">Curcumin</td>
<td align="center">Hydrogel<break/>Nanofiber</td>
<td align="center">&#xa0;Curcumin-loaded magnesium polyphenol network (Cur-Mg@PP)&#xa0;hydrogel<break/>mPEG-CUR loaded PVA/CS-g-PNVIS nanofibers</td>
<td align="center">Antimicrobial<break/>Antioxidant, Anti-inflammatory Analgesic, Angiogenesis<break/>Tissue regeneration</td>
<td align="center">Enhance biocompatibility<break/>Enable electrospinning process<break/>Structure mimics ECM<break/>Moist wound environment maintenance</td>
<td align="center">
<xref ref-type="bibr" rid="B25">Gong et al. (2023)</xref>; <xref ref-type="bibr" rid="B76">Shaabani et al. (2023)</xref>
</td>
</tr>
<tr>
<td align="center">Epigallocatechin gallate</td>
<td align="center">Injectable hydrogel</td>
<td align="center">GelMA/HA-E/Ag@MOF composite hydrogel</td>
<td align="center">Antibacterial/Anti-inflammatory<break/>Accelerated wound closure<break/>Angiogenesis promotion</td>
<td align="center">Macrophage polarization (M1&#x2192;M2)<break/>Activation Noncanonical Wnt pathway</td>
<td align="center">
<xref ref-type="bibr" rid="B105">Xiong et al. (2022)</xref>
</td>
</tr>
<tr>
<td align="center">Asiaticoside</td>
<td align="center">Injectable hydrogel</td>
<td align="center">rColMA/QCSG/LIP@AS/Ag@MOF (RQLAg) hydrogel</td>
<td align="center">Antibacterial<break/>Anti-inflammatory<break/>Accelerates wound healing</td>
<td align="center">Activate M1 macrophages<break/>Promote angiogenesis<break/>Enhance cell migration</td>
<td align="center">
<xref ref-type="bibr" rid="B21">Feng et al. (2023)</xref>
</td>
</tr>
<tr>
<td align="center">Alginate</td>
<td align="center">Core-shell nanofiber</td>
<td align="center">Asiaticoside-loaded nanofibers</td>
<td align="center">Antibacterial/Anti-inflammatory Angiogenesis promotion</td>
<td align="center">&#x2191;VEGF, CD31 expression<break/>&#x2193;TNF-&#x3b1;, IL-6<break/>Improve cell proliferation</td>
<td align="center">
<xref ref-type="bibr" rid="B126">Zhu et al. (2016)</xref>
</td>
</tr>
<tr>
<td align="center">Lavender active compound</td>
<td align="center">Electrospun nanofiber</td>
<td align="center">Alginate-lavender essential oil nanofibers</td>
<td align="center">Antibacterial,Anti-inflammatory<break/>UVB burn protection<break/>Prevent erythema formation<break/>Promote tissue regeneration</td>
<td align="center">Moist wound environment Biocompatibility<break/>Wound exudate management</td>
<td align="center">
<xref ref-type="bibr" rid="B29">Hajiali et al. (2016)</xref>
</td>
</tr>
<tr>
<td align="center">Bakuchiol</td>
<td align="center">Nanofibrous electrospun scaffold</td>
<td align="center">Bakuchiol nanoemulsion-loaded gelatin scaffold</td>
<td align="center">Antioxidant, Analgesic<break/>Enhanced wound healing<break/>Antibacterial, Anti-inflammatory</td>
<td align="center">Enhance BAK stability<break/>Controll drug release<break/>Uniform biomarker distribution</td>
<td align="center">
<xref ref-type="bibr" rid="B37">Kaur et al. (2024)</xref>
</td>
</tr>
</tbody>
</table>
</table-wrap>
<sec id="s3-1">
<title>Ointments</title>
<p>Ointments are a common dosage form for burn treatment, offering excellent adhesiveness and direct application to wounds. They prevent external stimuli and bacterial infections while providing anti-inflammatory, analgesic, and tissue-repairing effects. Moist Exposed Burn Ointment (MEBO), a patented TCM formulation, accelerates wound healing, exhibits antibacterial properties, and alleviates pain (<xref ref-type="bibr" rid="B53">Mabvuure et al., 2020</xref>). MEBO enhances granulation tissue formation, promotes the production of VEGF and bFGF, and activates epidermal stem cells (<xref ref-type="bibr" rid="B18">El-Hadidy et al., 2014</xref>; <xref ref-type="bibr" rid="B88">Tang et al., 2014</xref>). It also facilitates diabetic ulcer healing through autophagy and the PI3K-Akt-mTOR signaling pathway (<xref ref-type="bibr" rid="B122">Zheng et al., 2020</xref>). Aloe vera burn cream stimulates fibroblast and keratinocyte proliferation, significantly improving re-epithelialization rates and outperforming 1% sulfadiazine silver cream in treating second-degree burns (<xref ref-type="bibr" rid="B89">Teplicki et al., 2018</xref>; <xref ref-type="bibr" rid="B54">Mahboub et al., 2021</xref>).</p>
</sec>
<sec id="s3-2">
<title>Sprays</title>
<p>Sprays offer a convenient application method, reducing pain during drug administration and making them ideal for large-area burns. They form a breathable, elastic film on the wound surface, promoting granulation tissue growth. A spray formulation containing the extracts of <italic>Arnebia euchroma</italic> (Royle) Johnst.), <italic>Taraxacum mongolicum</italic> Hand.-Mazz., <italic>Phellodendron chinense</italic> Schneid. and borneol rapidly forms a protective film within 3&#x2013;5&#xa0;min. This film effectively shields wounds from contamination and infection while accelerating eschar formation (<xref ref-type="bibr" rid="B50">Liu et al., 2024</xref>). Autologous cell spray grafting, an innovative approach, uses a suspension of the patient&#x2019;s skin cells to treat deep burns, significantly enhancing re-epithelialization and wound healing (<xref ref-type="bibr" rid="B19">Esteban-Vives et al., 2016</xref>; <xref ref-type="bibr" rid="B77">Shree and Vagga, 2022</xref>).</p>
</sec>
<sec id="s3-3">
<title>Powders</title>
<p>Powders are simple to prepare and effectively absorb necrotic tissue from burn wounds. However, they may cause excessive crust formation and contamination risks. Sanhuang Powder, a classic TCM formula composed of <italic>Rheum palmatum</italic> L., <italic>Phellodendron chinense</italic> Schneid., and <italic>Coptis chinensis</italic> Franch., is used to clear heat and resolve toxins. Modern studies indicate that it also reduces the levels of pro-inflammatory cytokines, including IL-8 and GM-CSF (<xref ref-type="bibr" rid="B99">Wu et al., 2021</xref>). Jinhuang powder, a classic TCM surgical preparation, promotes fibroblast proliferation and migration via the Wnt/&#x3b2;-catenin signaling pathway, effectively treating diabetic foot wounds when combined with MEBO (<xref ref-type="bibr" rid="B113">Zhan et al., 2021</xref>; <xref ref-type="bibr" rid="B100">Wu M. et al., 2022</xref>).</p>
</sec>
<sec id="s3-4">
<title>Tinctures</title>
<p>Tinctures, which are herbal extracts dissolved in ethanol, facilitate easy monitoring of wounds; however, their irritant properties limit their application to first-degree burns. The Qi Wei Anti-burn Tincture, formulated with <italic>Phellodendron chinense</italic> C.K.Schneid., <italic>Melaleuca phoenicea</italic> (Lindl.) Craven and synthetic borneol, has been demonstrated to upregulate the expression of growth factors TGF-&#x3b2;1 and FGF-2, while downregulating the levels of pro-inflammatory mediators (TNF-&#x3b1;, IL-1&#x3b2;, IL-6) and reactive oxygen species in the livers of burned mice (<xref ref-type="bibr" rid="B17">Dinda et al., 2015</xref>; <xref ref-type="bibr" rid="B96">Wang S. et al., 2024</xref>).</p>
</sec>
<sec id="s3-5">
<title>Hydrogels</title>
<p>Hydrogels are highly promising for burn treatment due to their ability to adhere to uneven wound surfaces, inhibit bacterial growth, and reduce pain during dressing changes (<xref ref-type="bibr" rid="B82">Stoica et al., 2020</xref>). Multifunctional hydrogels derived from TCM active components offer antibacterial, anti-inflammatory, hemostatic, and tissue-regenerative properties (<xref ref-type="bibr" rid="B78">Shu et al., 2021</xref>). For example, a magnesium polyphenol network (Cur-Mg@PP) hydrogel loaded with curcumin demonstrates excellent therapeutic effects in pain relief, anti-inflammation, angiogenesis, and tissue regeneration (<xref ref-type="bibr" rid="B25">Gong et al., 2023</xref>). Another hydrogel loaded with epigallocatechin gallate exhibits dual antibacterial and anti-inflammatory properties, accelerating wound healing via the non-classical Wnt signaling pathway (<xref ref-type="bibr" rid="B105">Xiong et al., 2022</xref>). Additionally, a liposome-based hydrogel containing asiaticoside and superfine silver nanoparticles promotes cell migration, angiogenesis, and M1 macrophage polarization, effectively treating bacterial-infected burn wounds (<xref ref-type="bibr" rid="B21">Feng et al., 2023</xref>).</p>
</sec>
<sec id="s3-6">
<title>Nanofibers</title>
<p>Nanofibers loaded with bioactive compounds like curcumin and quercetin mimic the extracellular collagen matrix, supporting cell growth and accelerating burn wound healing (<xref ref-type="bibr" rid="B76">Shaabani et al., 2023</xref>). Asiaticoside-loaded nanofibers exhibit fast drug release and anti-inflammatory effects, significantly promoting healing in deep partial-thickness burns (<xref ref-type="bibr" rid="B126">Zhu et al., 2016</xref>). Alginate-lavender nanofibers possess antibacterial and anti-inflammatory properties, effectively treating burns by inhibiting <italic>Staphylococcus aureus</italic> growth and reducing inflammation in fibroblasts (<xref ref-type="bibr" rid="B29">Hajiali et al., 2016</xref>). Recent research shows that bakuchiol nanoemulsion-loaded gelatin scaffold exhibit significant analgesic, anti-inflammatory and wound healing promoting effects, and have potential application value in the treatment of burn wounds (<xref ref-type="bibr" rid="B37">Kaur et al., 2024</xref>).</p>
</sec>
<sec id="s3-7">
<title>Treatment of burn with TCM auxiliary therapies</title>
<p>In addition to TCM drugs and preparations, the TCM system includes unique therapies such as acupuncture, cupping, gua sha, tuina, and aromatherapy. These therapies complement conventional treatments, enhancing burn recovery and improving patients&#x2019; quality of life. Acupuncture, a cornerstone of TCM, plays a vital role in burn management. It alleviates pain, modulates inflammatory responses, promotes epithelialization and angiogenesis, and accelerates wound healing. A case study involving 1,008 burn patients demonstrated that acupuncture significantly improves wound healing outcomes in medical, economic, and biopsychosocial aspects (<xref ref-type="bibr" rid="B51">Loskotova and Loskotova, 2017</xref>). Acupoint stimulation therapy, a key form of acupuncture, modulates the neuroendocrine system by targeting specific acupoints such as Quchi, Hegu, Taichong, Xuehai, Sanyinjiao, and Zhiyang, reducing pain and inflammation. Electroacupuncture, which combines traditional acupuncture with electrical stimulation, enhances blood circulation, improves nerve conduction, reduces edema, and promotes wound healing. A randomized controlled trial showed that electroacupuncture at the bilateral Dingchuan acupoint improves lung function and diaphragm activity in patients with inhalation burns (<xref ref-type="bibr" rid="B2">Ali et al., 2022</xref>). Auricular therapy, targeting ear acupoints like Shenmen and Subcortical, effectively reduces pain, itching, and sleep disturbances in burn patients (<xref ref-type="bibr" rid="B11">Chen et al., 2021</xref>). Cupping induces local congestion through negative pressure, promoting blood circulation and lymphatic drainage. This process accelerates toxin elimination and generates anti-inflammatory, analgesic, and wound-healing effects. Before treatment, the burn area must be thoroughly cleaned, and key acupoints such as DU14 (Dazhui), LI11 (Quchi), and ST36 (Zusanli) are selected. Cupping can be performed using fire cups, air cups, or electric cups, followed by skin cleaning and medicinal cream application (<xref ref-type="bibr" rid="B1">Al-Bedah et al., 2019</xref>). Gua sha and tuina improve local blood circulation, enhance metabolic processes, relieve inflammation and edema, reduce pain, and promote wound healing. These manual therapies are particularly effective in managing burn-related discomfort and accelerating recovery (<xref ref-type="bibr" rid="B104">Xie et al., 2022</xref>). Aromatherapy utilizes plant essential oils extracted from flowers, leaves, and fruits to promote physical and mental wellbeing. It helps relax the nervous system, reduce stress, facilitate deep sleep, and alleviate the physical and mental stress caused by burns (<xref ref-type="bibr" rid="B43">Lee et al., 2021</xref>).</p>
</sec>
<sec id="s3-8">
<title>Combined treatment of burn with TCM and modern medicine</title>
<p>The integration of TCM and modern medicine represents a pivotal strategy in burn treatment, combining the strengths of both systems to optimize patient outcomes. Western medicine excels in rapid infection control, pain relief, and body temperature regulation, while TCM offers a holistic approach, minimal side effects, and favorable conditions for recovery. Together, they provide complementary benefits that address the multifaceted challenges of burn management. Modern medicine&#x2019;s dry therapy facilitates convenient wound observation and rapid healing by drying the wound and promoting scabbing, often followed by surgical or other reparative interventions. In contrast, TCM&#x2019;s moist therapy emphasizes moist wound repair, promotes physiological regeneration, and reduces scar formation. Additionally, traditional TCM therapies such as acupuncture and cupping play a distinctive role in alleviating pain, enhancing local blood circulation, and improving overall recovery. The research and development of TCM preparations further expand treatment options through the integration of TCM and modern medicine. However, several challenges remain. Firstly, the multifaceted components and diverse mechanisms of TCM make it difficult to fully elucidate its efficacy using modern medical standards. Secondly, inconsistent quality control standards in TCM may lead to batch-to-batch variations, affecting reproducibility and reliability. Finally, variations in treatment methods and medication practices between TCM and Western medicine necessitate enhanced communication and collaboration to bridge gaps and optimize integrated care.</p>
</sec>
</sec>
<sec sec-type="conclusion" id="s4">
<title>Conclusion</title>
<p>TCM has a long history and a well-established theoretical system for treating burn injuries, providing a robust foundation for modern scientific evaluation. As TCM modernization advances, the active ingredients and molecular mechanisms underlying its efficacy in burn treatment have been increasingly elucidated. This review explores the approaches and research progress in TCM for burn management, summarizing current TCM drugs, external preparations, adjunctive therapies, and their potential mechanisms. Regarding safety concerns, topical TCM applications for burn treatment generally demonstrate favorable safety profiles with minimal systemic side effects, owing to their localized administration and natural origins. However, vigilance remains essential as certain herbal components may cause local skin reactions, allergic responses, or interact with conventional therapies. High-dose applications of specific active ingredients, particularly alkaloids and anthraquinones, warrant careful consideration due to potential cytotoxic effects at elevated concentrations. Furthermore, the integration of TCM with modern burn therapies necessitates attention to potential pharmacological interactions, especially when combining herbal preparations with systemic medications.</p>
<p>Future research should prioritize comprehensive safety assessments, including long-term toxicity studies and drug interaction profiling, to establish evidence-based guidelines for safe clinical application. Most TCM burn treatments remain limited to animal models, highlighting the need for randomized, double-blind, placebo-controlled clinical trials in human patients to validate their efficacy and safety. Furthermore, the diversification of TCM external dosage forms, driven by advancements in pharmaceutical technology, presents both challenges and opportunities. Future research should focus on enhancing TCM preparation development, establishing systematic quality control systems, and improving therapeutic efficacy and safety. These efforts are essential for integrating TCM into mainstream burn treatment protocols and optimizing patient outcomes.</p>
</sec>
</body>
<back>
<sec sec-type="author-contributions" id="s5">
<title>Author contributions</title>
<p>YL: Writing &#x2013; original draft, Funding acquisition, Writing &#x2013; review and editing, Conceptualization. CY: Writing &#x2013; review and editing, Validation. TD: Writing &#x2013; review and editing, Software. YS: Writing &#x2013; review and editing. HL: Writing &#x2013; review and editing, Validation. ML: Data curation, Writing &#x2013; review and editing. WX: Writing &#x2013; review and editing. WZ: Writing &#x2013; review and editing. ZF: Writing &#x2013; review and editing. MH: Supervision, Writing &#x2013; review and editing. YZ: Writing &#x2013; review and editing, Supervision.</p>
</sec>
<sec sec-type="COI-statement" id="s7">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
<p>The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.</p>
</sec>
<sec sec-type="ai-statement" id="s8">
<title>Generative AI statement</title>
<p>The author(s) declare that no Generative AI was used in the creation of this manuscript.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p>
</sec>
<sec sec-type="disclaimer" id="s9">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<fn-group>
<fn fn-type="custom" custom-type="edited-by">
<p>
<bold>Edited by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1460255/overview">Mariangela Marrelli</ext-link>, University of Calabria, Italy</p>
</fn>
<fn fn-type="custom" custom-type="reviewed-by">
<p>
<bold>Reviewed by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2286432/overview">Francisco Cruz-Sosa</ext-link>, Universidad Aut&#xf3;noma Metropolitana, Mexico</p>
<p>
<ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3173034/overview">Maria Rosaria Perri</ext-link>, National Research Council of Italy, Italy</p>
</fn>
</fn-group>
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<sec id="s10">
<title>Glossary</title>
<def-list>
<def-item>
<term id="G1-fphar.2025.1651219">
<bold>TCM</bold>
</term>
<def>
<p>Traditional Chinese Medicine</p>
</def>
</def-item>
<def-item>
<term id="G2-fphar.2025.1651219">
<bold>TGF-&#x3b2;</bold>
</term>
<def>
<p>transforming growth factor-&#x3b2;</p>
</def>
</def-item>
<def-item>
<term id="G3-fphar.2025.1651219">
<bold>PDGF</bold>
</term>
<def>
<p>platelet-derived growth factor</p>
</def>
</def-item>
<def-item>
<term id="G4-fphar.2025.1651219">
<bold>EGF</bold>
</term>
<def>
<p>epidermal growth factor</p>
</def>
</def-item>
<def-item>
<term id="G5-fphar.2025.1651219">
<bold>FGF</bold>
</term>
<def>
<p>fibroblast growth factor</p>
</def>
</def-item>
<def-item>
<term id="G6-fphar.2025.1651219">
<bold>IL-8</bold>
</term>
<def>
<p>interleukin-8</p>
</def>
</def-item>
<def-item>
<term id="G7-fphar.2025.1651219">
<bold>IL-6</bold>
</term>
<def>
<p>interleukin-6</p>
</def>
</def-item>
<def-item>
<term id="G8-fphar.2025.1651219">
<bold>IL-1&#x3b2;</bold>
</term>
<def>
<p>interleukin-8</p>
</def>
</def-item>
<def-item>
<term id="G9-fphar.2025.1651219">
<bold>IL-2</bold>
</term>
<def>
<p>interleukin-8</p>
</def>
</def-item>
<def-item>
<term id="G10-fphar.2025.1651219">
<bold>IL-23</bold>
</term>
<def>
<p>interleukin-8</p>
</def>
</def-item>
<def-item>
<term id="G11-fphar.2025.1651219">
<bold>TNF-&#x3b1;</bold>
</term>
<def>
<p>tumor necrosis factor-alpha</p>
</def>
</def-item>
<def-item>
<term id="G12-fphar.2025.1651219">
<bold>VEGF</bold>
</term>
<def>
<p>vascular endothelial growth factor</p>
</def>
</def-item>
<def-item>
<term id="G13-fphar.2025.1651219">
<bold>ECM</bold>
</term>
<def>
<p>extracellular matrix</p>
</def>
</def-item>
<def-item>
<term id="G14-fphar.2025.1651219">
<bold>MMPs</bold>
</term>
<def>
<p>matrix metalloproteinases</p>
</def>
</def-item>
<def-item>
<term id="G15-fphar.2025.1651219">
<bold>RAO</bold>
</term>
<def>
<p>Radix arnebiae oil</p>
</def>
</def-item>
<def-item>
<term id="G16-fphar.2025.1651219">
<bold>SNK</bold>
</term>
<def>
<p>shikonin</p>
</def>
</def-item>
<def-item>
<term id="G17-fphar.2025.1651219">
<bold>HSFs</bold>
</term>
<def>
<p>hypertrophic scar-derived fibroblasts</p>
</def>
</def-item>
<def-item>
<term id="G18-fphar.2025.1651219">
<bold>MRSA</bold>
</term>
<def>
<p>methicillin-resistant <italic>Staphylococcus aureus</italic>
</p>
</def>
</def-item>
<def-item>
<term id="G19-fphar.2025.1651219">
<bold>SOD</bold>
</term>
<def>
<p>superoxide dismutase</p>
</def>
</def-item>
<def-item>
<term id="G20-fphar.2025.1651219">
<bold>IgA</bold>
</term>
<def>
<p>immunoglobulin A</p>
</def>
</def-item>
<def-item>
<term id="G21-fphar.2025.1651219">
<bold>HUVECs</bold>
</term>
<def>
<p>human umbilical vein endothelial cells</p>
</def>
</def-item>
<def-item>
<term id="G22-fphar.2025.1651219">
<bold>FA</bold>
</term>
<def>
<p>ferulic acid</p>
</def>
</def-item>
<def-item>
<term id="G23-fphar.2025.1651219">
<bold>BBR</bold>
</term>
<def>
<p>Berberine</p>
</def>
</def-item>
<def-item>
<term id="G24-fphar.2025.1651219">
<bold>MEBO</bold>
</term>
<def>
<p>Moist Exposed Burn Ointment</p>
</def>
</def-item>
<def-item>
<term id="G25-fphar.2025.1651219">
<bold>NO</bold>
</term>
<def>
<p>nitric oxide</p>
</def>
</def-item>
<def-item>
<term id="G26-fphar.2025.1651219">
<bold>NIR</bold>
</term>
<def>
<p>near-infrared</p>
</def>
</def-item>
<def-item>
<term id="G27-fphar.2025.1651219">
<bold>BNP</bold>
</term>
<def>
<p>bio-adhesive nanoparticles</p>
</def>
</def-item>
<def-item>
<term id="G28-fphar.2025.1651219">
<bold>PLA-HPG</bold>
</term>
<def>
<p>polylactic acid-hyperbranched polyglycerol</p>
</def>
</def-item>
<def-item>
<term id="G29-fphar.2025.1651219">
<bold>RCS/SF</bold>
</term>
<def>
<p>scaffold composed of cross-linked chitosan and rhubarb-derived charcoal</p>
</def>
</def-item>
<def-item>
<term id="G30-fphar.2025.1651219">
<bold>N-EMO</bold>
</term>
<def>
<p>nano-emodin</p>
</def>
</def-item>
<def-item>
<term id="G31-fphar.2025.1651219">
<bold>SDT</bold>
</term>
<def>
<p>photodynamic therapy</p>
</def>
</def-item>
<def-item>
<term id="G32-fphar.2025.1651219">
<bold>YHO</bold>
</term>
<def>
<p>Yuhong Ointment</p>
</def>
</def-item>
<def-item>
<term id="G33-fphar.2025.1651219">
<bold>ABTS</bold>
</term>
<def>
<p>2,2&#x2032;-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid)</p>
</def>
</def-item>
<def-item>
<term id="G34-fphar.2025.1651219">
<bold>DPPH</bold>
</term>
<def>
<p>1,1-Diphenyl-2-picrylhydrazyl radical</p>
</def>
</def-item>
<def-item>
<term id="G35-fphar.2025.1651219">
<bold>ATB</bold>
</term>
<def>
<p>antibiotic-free polysaccharide-based hydrogel dressing</p>
</def>
</def-item>
<def-item>
<term id="G36-fphar.2025.1651219">
<bold>Ber@MPs</bold>
</term>
<def>
<p>silk fibroin microspheres loaded with berberine</p>
</def>
</def-item>
<def-item>
<term id="G37-fphar.2025.1651219">
<bold>SOP</bold>
</term>
<def>
<p>polysaccharide</p>
</def>
</def-item>
<def-item>
<term id="G38-fphar.2025.1651219">
<bold>QUIBO1</bold>
</term>
<def>
<p>chitosan-based film containing 1% borneol</p>
</def>
</def-item>
<def-item>
<term id="G39-fphar.2025.1651219">
<bold>Cur-Mg@PP</bold>
</term>
<def>
<p>magnesium polyphenol network</p>
</def>
</def-item>
</def-list>
</sec>
</back>
</article>