Ultraviolet (UV) radiation is a primary oxidative stressor for skin (Rinnerthaler et al., 2015; Poplová et al., 2023). Sea buckthorn seed oil has demonstrated potential as a natural skin photoprotective metabolite, reducing UV irradiation-induced inflammatory responses by protecting the redox balance and lipid metabolism of skin cells, increasing antioxidant levels, and inhibiting the production of lipid peroxidation products. This effect is mediated through the upregulation of Nrf2 activity (Gęgotek et al., 2018). Further supporting this mechanism, a recent study utilizing primary human dermal fibroblasts (HDFs) and Balb/c mouse models revealed that Naringenin—a flavonoid isolated from sea buckthorn fruit pulp—effectively alleviates UV-B-induced oxidative stress and inflammation. Specifically, Naringenin reduced oxidative stress by scavenging reactive oxygen species (ROS) and upregulating key antioxidant enzymes, including catalase and Nrf2. Concurrently, it restored mitochondrial dynamics balance by reducing fragmentation and suppressed the phosphorylation of nuclear factor-kappa B (NF-κB), thereby blocking the production of pro-inflammatory cytokines (Sajeeda et al., 2024). Beyond this inhibitory effect on UV-induced inflammation, studies have also found that a sea buckthorn fruit mixture (SFB) can address skin aging issues caused by UV exposure, reducing wrinkles and improving skin texture, firmness, and hydration, while simultaneously downregulating the expression of matrix metallo proteinases (MMPs) and preventing oxidative and photo-damage (Hwang et al., 2012). Collectively, these findings underscore the crucial role of sea buckthorn-derived metabolites in mitigating skin oxidative stress, primarily via the Nrf2 antioxidant pathway.

Mucosal tissues are frequently exposed to oxidative challenges from various sources, including pathogens, chemicals, and drugs, which can lead to tissue damage and inflammation (Bhattacharyya et al., 2014). Evidence from studies on sea buckthorn demonstrates its potential to alleviate such oxidative stress. A study using a chronic obstructive pulmonary disease (COPD)-like mouse model established by long-term cigarette smoke exposure combined with intratracheal lipopolysaccharide (LPS) challenge confirmed that total flavonoids from sea buckthorn (TFSB) could alleviate inflammatory responses by activating the Nrf2 pathway and upregulating protective factors in the lungs (Xu et al., 2022). Furthermore, in a mouse model of LPS-induced acute lung injury, Sea buckthorn paste (SP), a traditional Tibetan medicine with high polyphenol content, significantly attenuated oxidative stress and lung tissue injury by promoting Nrf2 nuclear translocation and activation, manifested by suppressing the accumulation of the lipid peroxidation product malondialdehyde (MDA) and enhancing the levels of superoxide dismutase (SOD) and glutathione peroxidase (Du et al., 2017). Similarly, in a monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) rat model, Isorhamnetin (ISO)—a major natural flavonoid extracted from sea buckthorn—improved hemodynamic parameters and pulmonary vascular remodeling by upregulating Nrf2 protein expression in lung tissue, enhancing SOD activity, and inhibiting the NADPH oxidase 1 (NOX1) and p-c-src signaling pathways, thereby alleviating oxidative stress (Chen Y. et al., 2024).

In the digestive tract, in the context of Helicobacter pylori infection, sea buckthorn organic acid extracts (SOA) was shown to reduce ROS and pro-inflammatory cytokines, such as interleukin (IL)-β, IL-6, and IL-8, in gastric mucosal cells, indicating its direct role in countering oxidative and inflammatory pathways (Gao et al., 2025). Similarly, in rat models of methotrexate (MTX)-induced oral and oropharyngeal mucositis, sea buckthorn extract significantly lowered MDA levels—a marker of lipid peroxidation—and increased total glutathione (tGSH), an antioxidant, while suppressing inflammatory cytokines such as IL-1β and tumor necrosis factor -alpha (TNF-α) at both biochemical and gene expression levels (Dilber et al., 2023; Kuduban et al., 2016). Additionally, in an alcohol-induced intestinal barrier dysfunction model, flavonoids from Hippophae rhamnoides ssp. Sinensis seed residue (HRSF) attenuated oxidative stress (e.g., by inhibiting ROS and MDA accumulation and enhancing glutathione levels and SOD activity) and enhanced the expression of tight junction proteins (e.g., occludin and zona occludens 1 (ZO-1)) by modulating the Nrf2-mediated pathway, thereby protecting intestinal barrier integrity (Wei et al., 2023). Likewise, in high-fat diet (HFD)-fed zebrafish, Sea Buckthorn Polysaccharide (SP) enhanced the antioxidant capacity of the liver and intestine by upregulating Nrf2 expression (e.g., increasing Cu/Zn-SOD activity) and improved gut microbiota balance, thereby reducing lipid accumulation and inflammatory responses (Lan et al., 2022).

In skin inflammation, the NF-κB and MAPK pathways are activated in keratinocytes and immune cells by various triggers, driving pathologies like PSO and AD (Hao et al., 2023; Zhang et al., 2023; Ni et al., 2022; Yang et al., 2021). Sea buckthorn derivatives have been shown to target these pathways effectively. For instance, in a dinitrochlorobenzene (DNCB)-induced AD-like mouse model, topical application of sea buckthorn oil ameliorated dermatitis severity, reduced epidermal thickness, and suppressed mast cell infiltration by inhibiting NF-κB, janus kinase 2/signal transducer and activator of transcription 1 (JAK2/STAT1), and p38-MAPK signaling, thereby reducing the production of T helper cell 2 (Th2) chemokines thymus and activation-regulated chemokine (TARC) and MDC (Hou et al., 2017). Similarly, in a tissue plasminogen activator (TPA)-induced PSO-like model, sea buckthorn oil (SBKT) demonstrated anti-psoriatic efficacy by downregulating NF-κB expression and subsequent pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, leading to reduced ear edema and epidermal thickness (Balkrishna et al., 2019). Additionally, casuarinin, a tannin isolated from sea buckthorn, suppressed TNF-α/interferon (IFN)-γ-induced expression of TARC and MDC in human keratinocytes (HaCaT cells) by blocking p38 MAPK activation and subsequent inhibition of NF-κB and STAT1, highlighting its potential as a therapeutic agent for inflammatory skin diseases (Kwon et al., 2012).

In mucosal tissues, such as the intestine, these pathways are often triggered by microbial components (De Plaen et al., 2006; O'Mahony et al., 2008; Böhringer et al., 2016). Sea buckthorn metabolites exhibit protective effects by modulating these signaling cascades. For example, in LPS-induced porcine intestinal epithelial cells (IPEC-J2), pre-treatment with sea buckthorn polysaccharide (HRP) reduced inflammatory factors (e.g., IL-1β, IL-6, IL-8, TNF-α) and apoptosis while enhancing tight junction proteins and immunoglobulins, via inhibition of the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/NF-κB pathway (Zhao et al., 2020b). Proteomic analysis further confirmed that HRP pre-treatment alleviated LPS-induced inflammation by modulating differentially expressed proteins involved in immune-related pathways such as MAPK and NF-κB, with Western blotting validating the reduction in phosphorylated MAPK7, reticuloendotheliosis viral oncogene homolog A (RELA), NF-κB1, and NF-κB2 (Zhao et al., 2020a). In respiratory mucosa, TFSB prevented LPS/cigarette smoke-induced airway inflammation in mice and HBE16 bronchial epithelial cells by suppressing the expression of IL-1β, IL-6, chemokine (C-X-C motif) ligand 1 (CXCL1), and mucin 5 subtype AC (MUC5AC) through inhibition of extracellular regulated protein kinases (ERK), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and protein kinase C-alpha (PKCα) pathways, as supported by molecular docking studies showing binding affinities to upstream kinases (Ren et al., 2019).

Skin inflammation involves dysregulated crosstalk between various immune cells (Zouboulis et al., 2022; Honda and Kabashima, 2020). Sea buckthorn and its bioactive components have demonstrated efficacy in rebalancing immune responses in models of AD and PSO. For instance, in a DNCB-induced AD-like mouse model, topical application of sea buckthorn oil ameliorated dermatitis severity, reduced epidermal thickness, decreased spleen and lymph node weights, and suppressed mast cell infiltration, primarily through dose-dependent inhibition of Th2 chemokines TARC and MDC via NF-κB, JAK2/STAT1, and p38-MAPK signaling pathways (Hou et al., 2017). Similarly, in a PSO-like model induced by TPA in mice, sea buckthorn oil exhibited anti-inflammatory and anti-psoriatic effects by reducing ear edema and skin lesion scores, suppressing NF-κB activation, and inhibiting pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 (Balkrishna et al., 2019). Another key component, isorhamnetin (IRh), derived from sea buckthorn, alleviated imiquimod (IMQ)-induced psoriasiform lesions in mice by reducing oxidative stress (e.g., lowering MDA and restoring SOD and catalase (CAT) levels), suppressing pro-inflammatory cytokines (TNF-α, IL-6, IL-17A), and modulating T helper cell 1 (Th1) and T helper cell 17 (Th17) cell populations and dendritic cell maturation (Wu et al., 2022). Furthermore, topical application of total flavonoids from sea buckthorn (TFH) in an Calcipotriol (MC903)-induced AD model improved skin barrier function by upregulating filaggrin expression, reduced mast cell infiltration, and balanced Th1/Th2 cytokines (e.g., decreasing TNF-α, IL-4, IFN-γ, and thymic stromal lymphopoietin (TSLP)), while inhibiting NF-κB, ERK, and p38 signaling in keratinocytes (Gu et al., 2022). Additionally, extracts from sea buckthorn fruit peel showed anti-allergic effects in metabolite 48/80-induced paw edema by stabilizing mast cell membranes and inhibiting degranulation, with ursolic acid and oleanolic acid identified as active metabolites (Rédei et al., 2018). These studies collectively underscore sea buckthorn’s ability to modulate cutaneous immune responses through multiple pathways, including chemokine suppression, oxidative stress reduction, and cytokine network rebalancing.

Mucosal immunity is distinguished by its intimate interaction with the microbiota (Mowat and Agace, 2014; Shi et al., 2017). Sea buckthorn exerts regulatory effects on mucosal immunity by influencing gut microbiota composition, barrier function, and immune cell activity. In an intestinal model using colorectal adenocarcinoma (Caco-2)cells, an aqueous extract of sea buckthorn fruits inhibited LPS leakage through the epithelial monolayer, reduced pro-inflammatory cytokine secretion (e.g., IL-8, IL-1β, IL-6, TNF-α), and maintained glucose transporter protein 2 (GLUT2) expression, suggesting a role in preventing metabolic endotoxemia and low-grade inflammation (Laskowska et al., 2022). In a COPD rat model induced by LPS and smoking, Sea buckthorn Wuwei Pulvis (SWP)—a traditional Mongolian medicine containing sea buckthorn—improved pulmonary function (e.g., Forced Expiratory Volume (FEV)0.3/Forced Vital Capacity (FVC) ratio), reduced lung inflammatory cytokines (TNF-α, IL-8, IL-6, IL-17), and enhanced intestinal barrier integrity by upregulating tight junction proteins (ZO-1 and occludin-1). These effects were linked to modulation of gut microbiota (e.g., increased Ruminococcaceae and Christensenellaceae) and elevated short-chain fatty acid (SCFA) production (Wang et al., 2023). Moreover, in immunosuppressed mice induced by cyclophosphamide, sea buckthorn pulp oil enhanced systemic and mucosal immunity by promoting T lymphocyte proliferation, NK cell cytotoxicity, macrophage phagocytosis, and cytokine production (e.g., IFN-γ, IL-2, IL-4, IL-12, TNF-α, and secretory Immunoglobulin A (sIgA)). This was accompanied by increased SCFA levels and restoration of gut microbiota diversity, with elevated beneficial genera (e.g., Lactobacillus and Roseburia) and reduced pathobionts (e.g., Mucispirillum and Acinetobacter) (Zhang et al., 2021). In a zebrafish model of foodborne enteritis, sea buckthorn supplementation alleviated intestinal and hepatic inflammation by improving villi morphology, reducing immune cell infiltration (e.g., neutrophils and T cells), and modulating gut microbiota (e.g., reducing TM7 and Shigella). It also inhibited the p53 signaling pathway in the intestine while activating peroxisome proliferator activated receptor (PPAR) signaling and fatty acid metabolism in the liver, highlighting its role in gut-liver axis regulation (Li M. et al., 2022). These findings demonstrate that sea buckthorn stabilizes mucosal immunity by reinforcing barrier function, shaping microbial communities, and fine-tuning immune cell responses through SCFA and cytokine networks.

Skin repair involves re-epithelialization, collagen deposition, and angiogenesis (Sarate et al., 2024). Sea buckthorn extracts and oils have been extensively studied for their efficacy in enhancing these processes. For instance, seed oil enriched with saturated and unsaturated fatty acids, such as palmitic acid, promotes the proliferation of normal keratinocytes and skin fibroblasts, indicating regenerative properties on skin cells (Dudau et al., 2021). Topical application of sea buckthorn flavone accelerates wound contraction and epithelialization in rat models, as evidenced by reduced epithelialization time (16.3 days vs. 24.8 days in controls) (Gupta et al., 2006). Preclinical studies on leaf extracts further support wound healing, with polyvinyl alcohol-blended pectin hydrogel containing leaf extracts significantly reducing wound size and improving recovery rates in rats (Kim and Lee, 2017). In burn wound models, lyophilized aqueous leaf extract enhances collagen synthesis and stabilization, upregulates collagen type-III expression, and promotes angiogenesis via increased vascular endothelial growth factor (VEGF) expression, while also boosting antioxidant levels and reducing lipid peroxidation (Upadhyay N. K. et al., 2009). Similarly, supercritical CO₂-extracted seed oil augments burn wound healing by increasing wound contraction, hydroxyproline, hexosamine, DNA, and total protein content, up-regulating matrix metalloproteinases (MMP-2 and -9), collagen type-III (Upadhyay N. et al., 2009). In large animal models, seed oil application to full-thickness burns and donor sites in sheep significantly improves epithelization rates (95% ± 2.2% vs. 83% ± 2.9%) and shortens complete epithelization time (14.20 ± 0.48 days vs. 19.60 ± 0.40 days), confirming its efficacy in promoting re-epithelialization and graft healing (Ito et al., 2014). These findings collectively demonstrate that sea buckthorn components, including fatty acids, flavones, and leaf extracts, enhance skin repair through multiple mechanisms, including cell proliferation, collagen deposition, antioxidant activity, and angiogenesis.

Mucosal repair focuses on rapid epithelial renewal and restoration of barrier function (Chen et al., 2022; Kuo et al., 2021). Sea buckthorn has shown promise in accelerating mucosal healing, particularly in gastric ulcer models. CO2-extracted seed and pulp oils, when administered orally, significantly reduce ulcer formation in water-immersion and reserpine-induced models in rats, and accelerate the healing of acetic acid-induced gastric ulcers, indicating both preventive and curative effects (Xing et al., 2002). Further, sea buckthorn procyanidins (SBPC) from bark extract enhance the healing of acetic acid-induced gastric lesions by reducing ulcer size in a dose-dependent manner, increasing epidermal growth factor (EGF) levels in plasma, and up-regulating the expression of epidermal growth factor receptor (EGFR) and proliferating cell nuclear antigen (PCNA) around the ulcer site, which promotes mucosal repair and epithelial renewal (Xu et al., 2007). These studies highlight the role of sea buckthorn oils and procyanidins in restoring mucosal integrity through enhanced epithelial cell proliferation and growth factor signaling. Table 1 presents the experimental models and mechanisms of skin and mucosal inflammation modulation by sea buckthorn and its derivatives.