Sesquiterpenoids, as one of the active ingredients of agarwood, are formed by three isoprene units, and its content in agarwood extracts is high, accounting for 52% of the chemical composition of agarwood (Chen et al., 2012). It can be regarded as a criterion for grading the quality of agarwood. More than 210 sesquiterpenes have been extracted from agarwood, which can be categorized into eight main types (Smiley et al., 2015). Sesquiterpenes from agarwood exhibit a wide range of pharmacological effects, including anti-inflammatory, anti-tumor, antibacterial activities, inhibition of glycosidase, and regulation of the central nervous system (Wang Y. et al., 2022; Chen X. et al., 2022; Yang et al., 2019). A study by Xie demonstrated that sesquiterpenes from agarwood have significant anti-inflammatory activity, with an IC50 value for NO in lipopolysaccharide-induced RAW264.7 cells ranging from 5.46 to 14.07 μM (using aminoguanidine as a positive control with an IC50 of 20.33 ± 1.08 μM) (Xie et al., 2021). Huang’s research showed that sesquiterpenes from agarwood are effective against tumors and malaria (Huang X. L. et al., 2023). Additionally, the 2-(2-phenylethyl) chromone-sesterterpene hybrid compounds found in agarwood have protective effects on gastric mucosal cells and may be used to treat renal fibrosis by inhibiting the phosphorylation of Smad 3 (Huang et al., 2022; Zhang et al., 2023).

2-(2-Phenylethyl) chromone is synthesized through the substitution of the phenylethyl moiety at the C-2 position of the chromogenic ketone, which accounts for 41% of the content in agarwood (Lee and Mohamed, 2016). The high cost of obtaining agarwood samples and chromone standards presents a significant challenge in the identification of agarwood chromone derivatives. To address this, Du has developed an enhanced data integration and filtering strategy that provides a detailed characterization and summary of the characteristic fragments and cleavage rules for 2-(2-phenylethyl) chromone monomers and their dimers, which introduces a novel research approach for the identification of agarwood chromone monomers and dimers (Li W. et al., 2021). As a principal bioactive constituent of agarwood, 2-(2-Phenylethyl)chromone exhibits a wide range of therapeutic properties, including anti-inflammatory, anti-tumor, neuroprotective functions, and the inhibition of acetylcholinesterase and glucosidases (Chen et al., 2012). The 2-(2-phenylethyl)chromone derivatives extracted from agarwood exhibit significant inhibitory effects on α-glucosidase, with IC50 values ranging from 7.8 ± 0.3 to 137.7 ± 3.0 μM (Acarbose, 743.4 ± 3.3 μM; Genistein, 8.3 ± 0.1 μM) (Wang Y. et al., 2022). Sarmah utilized computational simulation methods such as molecular docking, absorption, distribution, metabolism, excretion, toxicity, and molecular dynamics to discover that 2-(2-phenylethyl) chromone from agarwood can efficiently inhibit cyclooxygenase (COX) and lipoxygenase (LOX), with a higher affinity compared to ibuprofen, which suggests its potential as an effective inhibitor for the treatment of inflammatory diseases (Yang et al., 2019). Agarwood possesses unique advantages in the treatment of cardiovascular diseases. Derivatives of 2-(2-phenylethyl) chromone have been shown to mitigate the expression of CD36 in macrophages mediated by endoplasmic reticulum stress, thereby inhibiting the formation of foam cells and exerting a therapeutic effect on atherosclerosis (Chen L. et al., 2022). This mechanism of action represents a promising approach in the management of cardiovascular conditions, where the regulation of cellular processes and inflammation plays a pivotal role. The ability of these chromone derivatives to modulate key pathways involved in atherosclerotic plaque development highlights their potential as novel therapeutic agents. In addition, research by Ma has demonstrated that agarwood extracts rich in 2-(2-phenylethyl)chromone can ameliorate taurocholic acid-induced apoptosis in gastric epithelial cells by modulating endoplasmic reticulum stress, thereby exhibiting therapeutic efficacy against bile reflux gastritis (Xie et al., 2021). This finding underscores the potential of 2-(2-phenylethyl) chromone-enriched agarwood extracts in treating gastrointestinal conditions, particularly those characterized by cellular damage and inflammatory responses.

Agarwood has a long-standing history in aromatherapy (Huang X. L. et al., 2023), where its unique fragrance emitted upon heating is known for its beneficial effects on sleep disorders. The smoke from burning agarwood contains a significant amount of LACs, which, when inhaled, can aid in sleep induction and improvement (Huang et al., 2022). Benzyl acetone is a key component responsible for the sedative effects (Zhang et al., 2023). Research by Castro has indicated that while LACs from agarwood exhibit sedative potential when inhaled individually, the combined use of these compounds results in a diminished sedative effect (Castro and Ito, 2021). This reduction in efficacy may be attributed to antagonistic actions due to the structural similarities among the LACs (Table 1).

As mentioned above, the natural formation of agarwood has several drawbacks, making the technology of artificial induction of agarwood a key solution to address the issues mentioned above, with the aim of increasing agarwood production to meet market demand. With the advancement of technology, the quality of artificially induced agarwood has significantly improved. Research by Ma has shown that the chemical composition of artificially induced agarwood is similar to that of wild agarwood, and its antioxidant properties, as well as its ability to inhibit glucosidase and acetylcholinesterase, are comparable to those of wild agarwood (Ma et al., 2023).

The artificial induction of agarwood formation is primarily categorized into traditional methods, biological induction, and chemical induction (Yan et al., 2019). Traditional methods involve creating wounds on the tree through manual drilling, hole-making, burning, or chopping to simulate the natural conditions under which a tree would be injured, thereby inducing resin secretion and the formation of agarwood. The advantage of these methods is that they do not require guidance from specialized technical personnel. However, the downside is that agarwood is formed only locally at the site of injury, leading to inconsistent yields and average quality (Azren et al., 2018). Xu’s research on the dynamic response of agarwood to mechanical damage has revealed the molecular mechanisms behind agarwood formation, providing a new reference for the quality assessment of agarwood (Xu et al., 2023).

Artificial biological induction involves drilling into the tree and implanting biological inducers to simulate the natural infection of trees. However, not all microorganisms are capable of inducing healthy agarwood trees to form agarwood. Commonly used fungal species include Fusarium, Lasiodiplodia, Penicillium, and Aspergillus (Chen et al., 2017; Sangareswari Nagajothi et al., 2016). Phaeoacremonium rubrigenum can promote the accumulation of sesquiterpene compounds in agarwood by inducing plant host phosphorylation (Liu et al., 2022). Huang has demonstrated that agarwood induced artificially using fungal inducers prepared from wild agarwood is similar in quality to wild agarwood (Huang M. et al., 2023). Wu has developed the Biologically Agarwood-Inducing Technique (Agar-Bit), where biological inducers are injected into the heartwood part of the agarwood tree (Wu and Yu, 2023). This method can induce agarwood formation within 6 months while maintaining the health and vitality of the tree, offering a new approach to whole-tree agarwood induction. The advantages of biological induction include low cost and ease of operation. However, the downside is the potential inconsistency in agarwood quality due to variations in microbial populations at the inoculation sites (Naziz et al., 2019).

When it was discovered that certain signaling molecules could trigger the defense response of agarwood trees, promoting the secretion of resin components in healthy agarwood to resist external stimuli, chemical induction became a new research hotspot (Wu et al., 2024). Chemical induction can solve the problem of poor repeatability in the quality of agarwood formed through biological induction, and it appears to be the most ideal and reliable alternative to natural agarwood formation.

Chemical induction can solve the problem of poor reproducibility of agarwood formation quality in biological induction and seems to be the most ideal and reliable alternative to natural agarwood formation. Chemical induction refers to the direct application of chemical agents such as ferrous chloride, hydrogen peroxide, and methyl jasmonate to trees to induce agarwood formation. For example, hydrogen peroxide promotes programmed cell death in agarwood and the accumulation of salicylic acid and sesquiterpene compounds (Lv et al., 2019; Liu et al., 2015). Methyl jasmonate promotes the formation of sesquiterpene compounds in agarwood (Xu et al., 2016; Sun P. W. et al., 2020). Currently, several techniques for chemical induction of agarwood have been developed, such as the Cultivated Agarwood Kit (CA-kit), Biological Agarwood Induction Technology (Agar-bit), and Whole-Tree Agarwood Induction Technology (Agar-Wit) (Tan et al., 2019). The advantages of chemical induction include convenient operation, stable and reliable agarwood quality, and the ability to induce the entire tree. However, the downside is that it can easily cause tree rot, high concentrations of chemical agents can cause the death of the tree, and the potential environmental hazards of chemical agents must still be considered (Azren et al., 2018; Faizal et al., 2021). Therefore, before the large-scale promotion of the chemical induction method, extensive experiments are still needed to verify its safety and feasibility repeatedly (Table 2).

Inflammatory response refers to maintaining homeostasis by eliminating pathogenic microorganisms through intrinsic and adaptive immune responses when pathogenic microorganisms stimulate the organism. There has been a significant amount of research on the anti-inflammatory effects of agarwood essential oil against inflammatory diseases, and the anti-inflammatory effects of agarwood are attributed to its ability to modulate the production of inflammatory mediators and reduce oxidative stress, which are critical factors in the pathogenesis of various inflammatory diseases (Alamil et al., 2022). As previously mentioned, sesquiterpenes and 2-(2-phenylethyl) chromone compounds exhibit potent anti-inflammatory activities. Numerous vitro studies have demonstrated that sesquiterpene compounds isolated from agarwood can effectively inhibit the release of nitric oxide by macrophages induced by lipopolysaccharide (Xie et al., 2021; Zhao et al., 2016; Hu et al., 2024). However, the specific mechanisms by which sesquiterpene compounds exert their anti-inflammatory effects remain to be elucidated. In contrast, 2-(2-phenylethyl) chromone compounds have been shown to suppress the release of nitric oxide in RAW 264.7 cells during inflammation by inhibiting the activation of NF-κB without cytotoxicity (Wang S. L. et al., 2018; Yu et al., 2020; Yang et al., 2023). Additionally, 2-(2-phenylethyl)chromone compounds can inhibit the release of inflammatory mediators such as NO, TNF-α, IL-6, IL-1β, and PGE2 by suppressing the STAT and MAPK signaling pathways (Zhu et al., 2016a). Gao administered agarwood essential oil via gavage, effectively suppressing ear edema induced by dimethyl benzene and foot edema caused by carrageenan (Gao et al., 2019). This anti-inflammatory effect may be associated with the inhibition of p-STAT3 protein expression. In addition, agarwood extracts have been shown to provide protective effects against gastric ulcers and intestinal mucositis by suppressing inflammatory responses and alleviating anxiety symptoms (Wang C. et al., 2021; Zheng et al., 2019; Wang S. et al., 2018). Inflammatory responses are closely related to conditions such as cancer and immune reactions, and agarwood has demonstrated inhibitory effects on various inflammatory diseases, which could potentially validate the broad pharmacological activities of agarwood from a different perspective (Table 3).

Chronic respiratory diseases such as chronic obstructive pulmonary disease and asthma often exhibit pathological characteristics of oxidative stress and inflammatory responses. Agarwood essential oil, rich in functionally active components such as sesquiterpenes and 2-(2-phenylethyl) chromones, can be a potential source of antioxidant active materials. Chen’s research indicates that agarwood essential oil’s DPPH and ABTS radical scavenging abilities are positively correlated with concentration (Chen L. et al., 2022). At a 5 mg/mL concentration, agarwood essential oil obtained by supercritical extraction exhibited a DPPH radical scavenging rate of over 50%. At a concentration of 2 mg/mL, the ABTS radical scavenging rate ranged from 53.03% to 83.26%. Ma’s research shows that the DPPH and ABTS radical scavenging capabilities of Induced agarwood (IA) and wild agarwood (WA) are close (Ma et al., 2023). At a concentration of 0.8 mg/mL, the DPPH radical scavenging rates for IA and WA were 91.26% and 91.59%, respectively. At 0.2 mg/mL, the ABTS radical scavenging rates for IA and WA were 91.03% and 94.80%, respectively.

Due to the poor solubility and low bioavailability of agarwood essential oil, these factors have become barriers to its clinical application and promotion. To address this issue, Rubis utilized ultrasonication to prepare agarwood essential oil into a nanoemulsion, investigating its potential antioxidant and anti-inflammatory effects on airway basal epithelial cells under cigarette smoke extract stimulation. The experimental results showed that the agarwood nanoemulsion could inhibit oxidative stress by inducing the expression of antioxidant genes and exert protective effects by suppressing inflammatory responses, demonstrating the therapeutic potential of agarwood for chronic obstructive pulmonary disease (De Rubis et al., 2023). In further research, Malik prepared agarwood oil nanoemulsions and explored its antioxidant and anti-inflammatory capabilities on lipopolysaccharide-induced RAW264.7 macrophages. The results demonstrated that the agarwood oil nanoemulsions significantly reduced the production of reactive oxygen species (ROS) and the expression of the antioxidant gene heme oxygenase-1 (HO-1), revealing a strong antioxidant potential (Malik et al., 2023). In addition to the studies above, Wang prepared an animal model of alcoholic fatty liver disease and found that agarwood extract could effectively reduce the expression levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and cholesterol (CHO), lower blood lipid levels, and improve liver function through its antioxidant effects, alleviating the damage to the liver caused by a high-fat diet and alcohol consumption (Wang et al., 2023). Through in vivo studies on the effects of agarwood extracts on myocardial ischemia, Wang discovered that agarwood extracts could upregulate and activate the Nrf2-ARE pathway, exhibiting significant antioxidant effects, thereby playing a protective role against myocardial infarction (Wang et al., 2020) (Table 4).

The antibacterial activity of agarwood is beneficial in combating bacterial and fungal infections. An increasing body of research in vitro has demonstrated that agarwood essential oil exhibits significant inhibitory effects against Staphylococcus aureus and Bacillus subtilis (Chen et al., 2011). Dahham isolated β-caryophyllene from agarwood essential oil and investigated its antimicrobial and antioxidant properties. In vitro, experimental results indicated that β-caryophyllene present in agarwood has notable antibacterial effects against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Moreover, its antifungal activity against Trichoderma reesei is superior to that of kanamycin (Dahham et al., 2015). Hu compared the antimicrobial activity of smoke produced by burning both Qi-Nan agarwood and ordinary agarwood (induced by the knife-cutting method), revealing that both demonstrated potent antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, with Qi-Nan agarwood showing greater efficacy than ordinary agarwood (Hu et al., 2023). Nurminah’s research suggested that agarwood distillate water extracts also possess inhibitory effects on Streptococcus mutans in vitro (Nurminah et al., 2021) (Table 5).

Aromatherapy has long been utilized to relax the mind and body and relieve stress. Agarwood essential oil, known for its unique aromatic scent and practical components, is commonly used in the treatment of insomnia, anxiety, and depression, offering distinct advantages in the treatment of psychiatric disorders. Agarwood emits a distinctive fragrance when heated, and inhaling the smoke generated can help with sleep induction and improve sleep disorders (Wang C. et al., 2022). Agarwood essential oil is also calming by regulating the expression of GABA_A receptors and enhancing receptor function (Wang et al., 2017). Through experiments such as the light-dark box test and the tail suspension test, Wang found that agarwood essential oil may exert anxiolytic and antidepressant effects by inhibiting the release of corticotropin-releasing factor and the activation of the hypothalamic-pituitary-adrenal (HPA) axis, with effects similar to those of diazepam (2.5 mg/kg) (Wang S. et al., 2018). Li, through preparing a mixed essential volatile oil of Aquilaria sinensis (Lour.) Gilg and Aucklandia costus Falc, arrived at conclusions consistent with those of Wang’s research (Li H. et al., 2021). Using network pharmacology combined with solid-phase microextraction/gas chromatography-time of flight mass spectrometry, Pang discovered that sesquiterpenes in agarwood can exert anxiolytic effects by acting on multiple targets and signaling pathways (Pang et al., 2024). Han, through the injection of scopolamine to induce a model of learning and memory impairments, demonstrated significant alleviation of symptoms after inhalation of agarwood smoke (Han et al., 2021) (Table 6).

Agarwood’s anti-tumor effects are of interest in oncology, as it may inhibit tumor growth and induce apoptosis in cancer cells. Studies have indicated that oral administration of agarwood essential oil at doses of 100 mg/kg and 500 mg/kg for 28 consecutive days had no significant impact on the vital signs of mice. However, it exhibited inhibitory effects on the growth of colon cancer cells (Dahham et al., 2016). As its active constituents, the sesquiterpenes and chromone compounds in agarwood have also been extensively studied for their cytotoxicity. A new sesquiterpene compound was isolated from Aquilaria sinensis, which exhibited strong sensitivity to breast cancer cells. The relevant mechanism may be promoting the expression of reactive oxygen species (ROS) in cells, which promotes cancer cell apoptosis. This compound could potentially become a promising anticancer agent (Chen L. et al., 2022). Utilizing LC-MS-guided fractionation, Chen obtained five new derivatives of 2-(2-phenylethyl) chromone, which significantly inhibited the growth of five types of human cancer cells (IC50 13.40–28.96 μM), with cisplatin serving as a positive control (IC50 3.08–11.29 μM) (Chen et al., 2023). Similar findings were observed in cytotoxicity studies of 2-(2-phenylethyl) chromone derivatives isolated from agarwood (Xia et al., 2019). β-Caryophyllene isolated from the essential oil of Aquilaria crassna effectively inhibited the proliferation, migration, invasion, and spheroid formation of colorectal cancer cells (Dahham et al., 2015) (Table 7).

As a key enzyme in glucose metabolism, α-glucosidase has the dual role of hydrolysis and transglycosidation in the catalytic reaction of sugar. Inhibition of α-glucosidase can effectively improve the efficiency of glucose absorption in the intestine, ameliorate postprandial blood glucose levels, and exert effects in delaying the progression of diabetes. The active component of agarwood, 2-(2-phenylethyl)chromone derivatives, possesses significant inhibitory effects on α-glucosidase (IC50 7.8 ± 0.3–137.7 ± 3.0 μM), which is more potent than acarbose (IC50 743.4 ± 3.3 μM) (Mi et al., 2021). Sesquiterpenes in agarwood also exhibit inhibitory effects on α-glucosidase, with effects superior to acarbose (Mi et al., 2019; Yang et al., 2019). Furthermore, phenethyl chromone compounds from agarwood may improve diabetes by modulating adiponectin secretion (Ahn et al., 2019) (Table 8).

Acetylcholinesterase (AChE) is responsible for the breakdown of acetylcholine at synaptic junctions, terminating the excitatory action of the neurotransmitter on the postsynaptic membrane. The deficiency of acetylcholine is a primary cause of Alzheimer’s disease, and the inhibition of AChE can slow the progression of the condition. The compound 5,6,7,8-Tetrahydro-2-(2-phenylethyl)chromones, isolated from agarwood, has been found to exhibit potent inhibitory effects against AChE, with an inhibition rate of up to 47.9% (with tacrine as a positive control, showing an inhibition rate of 66.7%) (Liao et al., 2017). Epoxy-5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones, isolated from agarwood by Li, also demonstrated significant inhibitory activity, with an AChE inhibition rate of 47.9% ± 0.3% at a concentration of 50 μg/mL (Li et al., 2019). In contrast, 2-(2-phenylethyl) chromone derivatives isolated by Chen, Yang, and others from agarwood exhibited weaker inhibitory activity, with inhibition rates ranging from 12.0% to 15.7% (Yang et al., 2017; Yang et al., 2014) (Table 9).

In addition to the aforementioned pharmacological effects, agarwood possesses various other pharmacological properties, including immune modulation, neuroprotection, and gastrointestinal protection.

The agarwood epoxy compound 2-(2-phenylethyl) chromone derivative (GYF-21) can inhibit both innate and adaptive immune responses by suppressing the STAT1/3 and NF-κB signaling pathways, making it a potential candidate for the treatment of multiple sclerosis (Guo et al., 2017). GYF-21 can also inhibit B cells’ activation, proliferation, and differentiation functions by inhibiting the BAFF signaling pathway, offering potential therapeutic effects for systemic lupus erythematosus (Guo et al., 2019). Furthermore, the sesquiterpene derivative from agarwood (HHX-5) can regulate immune responses by inhibiting macrophage activation, CD4⁺ T cell differentiation, and B cell activation by suppressing the STAT pathway (Zhu et al., 2016b). Also, the hybrid of agarwood 2-(2-phenylethyl)chromone-sesquiterpene can protect gastric mucosal cells by downregulating endoplasmic reticulum stress induced by taurocholic acid (Zhang et al., 2023). The dimer of sesquiterpenes from agarwood wood also exhibits antimalarial effects (IC50 21.67 ± 1.25 nM), with artemisinin serving as a positive control (IC50 559.4 ± 66.55 nM) (Huang X. L. et al., 2023). Agarwood also has therapeutic effects in treating cardiovascular diseases, where 2-(2-phenylethyl) chromone derivatives can mitigate atherosclerosis by reducing endoplasmic reticulum stress-mediated macrophage CD36 expression and inhibiting foam cell formation (Ma et al., 2024).

Macrophages play a crucial role in maintaining homeostasis and defense in periodontal tissues. However, their excessive aggregation and activation can damage periodontal tissue. Under the stimulation of pathogenic microorganisms and inflammatory cells, macrophages can polarize into M1 type macrophages through the STAT 1 signaling pathway (Han et al., 2020; Wang W. et al., 2021), and secrete inflammatory factors such as PGE2, TNF-α, IL-1β, IL-6, and iNOS. PGE2 is the most potent cytokine in promoting periodontal bone destruction, which can mediate destructive processes of alveolar bone and cementum by downregulating the mineralization ability of osteoblasts and promoting osteoclast formation (Oka et al., 2007). TNF-α, IL-1β, and IL-6 primarily stimulate the chemotaxis and migration of inflammatory cells to periodontal tissues, enhance the expression of neutrophil adhesion factors on the vascular surface, and augment the synthesis of other pro-inflammatory cytokines. They also exert destructive effects on bone and connective tissues by promoting the expression of MMPs and RANKL (Cekici et al., 2014). iNOS can catalyze NO production from L-arginine until the substrate is depleted (Fretwurst et al., 2020). Low NO concentrations within the periodontal tissue are beneficial for exerting anti-inflammatory effects. In contrast, high NO concentrations can exacerbate inflammatory responses caused by bacteria and endotoxins, accelerating the destruction of alveolar bone (Sun S. et al., 2020). Zhu investigated the anti-inflammatory activity of agarwood 2-(2-phenylethyl)chromone derivative (GYF-17) against LPS-induced RAW264.7 cells and its potential mechanisms, and the results showed that GYF-17 could reduce the expression of iNOS induced by LPS and downregulate the release of NO. In addition, GYF-17 significantly inhibited the expression and secretion of vital pro-inflammatory factors such as IL-1β, IL-6, PGE2, and TNF-α (Zhu et al., 2016a). Wang’s research indicates that agarwood extract can effectively reduce the expression levels of inflammatory cytokines such as TNF-α and IL-6 (Wang et al., 2023).

In states of inflammation, CD4⁺ T cells in the periodontal tissue can proliferate and differentiate into various subtypes of Th cells, such as Th1, Th2, and Th17. Th1 cells, characterized by their role in cell-mediated immunity, can lead to alveolar bone resorption and promote the progression of periodontal inflammation by releasing IFN-γ, IL-2, and RANKL. Th17 cells produce vital cytokines such as IL-17, which plays a positive role in bone remodeling and homeostasis (Yu et al., 2007). However, excessive IL-17 production can exacerbate periodontal tissue destruction by upregulating the expression of chemokine ligands (CXCL1, CXCL2, and CXCL5), IL-1β, MMPs, granulocyte colony-stimulating factors (G-CSF) and granulocyte-macrophage colony-stimulating factors (GM-CSF) (Veldhoen, 2017). The upregulation of G-CSF and GM-CSF increases tissue permeability, mediating chemotaxis and activation in periodontal tissues, thereby exacerbating damage through phagocytosis and cellular immunity.

In periodontitis patients, the proportion of B cells in the lesion tissue correlates positively with the severity of periodontitis (Reinhardt et al., 1988). Under the stimulation of pathogenic microorganisms, B cells perform antigen presentation to trigger immune responses in CD4⁺ T cells and differentiate themselves into plasma cells that secrete immunoglobulins to neutralize antigens. B cells can also produce inflammatory cytokines such as TGF-β, TNF-α, IL-10, and IL-6 to modulate inflammatory responses and generate matrix metalloproteinases (MMPs), which are crucial in physiological and pathological processes. Collagenases like MMP-1 and MMP-8 can dissolve types I, II, and III collagen fibers, leading to collagen dissolution and periodontal connective tissue destruction (Zou et al., 2022; Nędzi-Góra et al., 2021; Luchian et al., 2022). B cell activating factor (BAFF) plays a critical regulatory role, enhancing B cell survival, proliferation, and antigen presentation by binding to receptors, including BAFFR, and promoting plasma cell differentiation. As mentioned earlier, agarwood possesses significant immunomodulatory functions, and its active components could potentially serve as a source of immunosuppressive agents. The sesquiterpene derivative from agarwood (HHX-5) can effectively inhibit the activation, proliferation, and differentiation of CD4⁺ and CD8⁺ T cells, thereby suppressing cell-mediated immune responses (Zhu et al., 2016b). Furthermore, the 2-(2-phenylethyl) chromone derivative from agarwood (GYF-21) can inhibit B cells’ activation, proliferation, and differentiation by blocking the signaling pathway activated by BAFF (Guo et al., 2019).