Background and Purpose: Psoriasis is an inflammatory skin disease of chronic recurrence mediated by the interaction between IL‐17 and keratinocytes, which sustains a vicious circle of inflammation. Safe and effective natural medicine is a potential strategy for the clinical treatment of psoriasis. Given its prominent anti‐proliferative and anti‐inflammatory properties, we investigated the actions of allicin in improving psoriasis.Experimental Approach: Pharmacodynamic studies were carried out in mice after topical administration of allicin against psoriasis‐like lesions induced by imiquimod. Skin sensitization tests were evaluated on guinea pigs. Toxicological studies and skin irritation tests were assessed by consecutive topical allicin alone on the skin of rabbits. RNA‐seq probed transcriptomic changes following allicin. Western blot explored the actions of allicin on the interaction between IL‐17A and keratinocytes. Changes in inflammatory factor expression were analysed by qPCR and immunohistochemistry.Key Results: Allicin significantly improved the epidermal structure by inhibiting the excessive proliferation and reduced apoptosis of keratinocytes. Furthermore, allicin reduced the secretion of inflammatory cytokines (IL‐17A/F, IL‐22, IL‐12, and IL‐20), chemokines (CXCL2, CXCL5, and CCL20), and anti‐bacterial peptides (S100a8/9). Mechanistically, allicin directly inhibited the IL‐17‐induced TRAF6/MAPK/NF‐κB and STAT3/NF‐κB signalling cascades in keratinocytes, thus breaking the positive inflammatory feedback and alleviating imiquimod‐induced psoriasis‐like dermatitis in mice. Importantly, topical administration of allicin did not cause skin allergy, and the safety and adaptability of long‐term application were verified.Conclusions and Implications: Interfering with IL‐17 signalling in keratinocytes with allicin is a promising strategy for treating psoriasis, given its safety and effectiveness.
Objective: This study assessed the major nutrients and antioxidant properties of Berberis heteropoda Schrenk fruits collected from the Nanshan Mountain area of Urumqi City, Xinjiang Uygur Autonomous Region, China. Methods and materials: We assessed the basic nutrients, including amino acids, minerals, and fatty acids, and determined the total phenol, flavonoid, and anthocyanin contents of the extracts. Results: The analytical results revealed the average water (75.22 g/100 g), total fat (0.506 g/100 g), total protein (2.55 g/100 g), ash (1.31 g/100 g), and carbohydrate (17.72 g/100 g) contents in fresh B. heteropoda fruit, with total phenol, flavonoid, and anthocyanin contents of B. heteropoda fruits at 68.55 mg gallic acid equivalents/g, 108.42 mg quercetin equivalents/g, and 19.83 mg cyanidin-3-glucoside equivalent/g, respectively. Additionally, UPLC-Q-TOF-MSE analysis of polyphenols in B. heteropoda fruit revealed 32 compounds. Conclusion: B. heteropoda fruits may have potential nutraceutical value and represent a potential source of nutrition and antioxidant phytochemicals in the human diet.
Three new polycyclic polyprenylated acylphloroglucinol derivatives, hyperacmosins H-J (1–3), with four known compounds (4–7), were isolated from the air-dried aerial parts of Hypericum acmosepalum. Especially, compounds 1 and 2 were identified as methylated polycyclic polyprenylated acylphloroglucinol derivatives (mPPAPs). Their structures were established by NMR, HRESIMS and experimental electronic circular dichroism (ECD) spectra. The hepatoprotective activity of seven compounds were evaluated. Compounds 1 and 5 exhibited hepatoprotective activity against paracetamol-induced HepG2 cell damage.
Background/Objectives: Astragalus root is a classical qi-tonifying traditional Chinese medicine that has demonstrated potential therapeutic efficacy in type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). However, the precise mechanisms underlying its effects on the comorbidity of these two disorders remain unclear. This study investigated the molecular mechanisms by which Astragalus root ameliorated T2DM-NAFLD comorbidity. Methods: Network pharmacology, molecular docking, molecular dynamics simulation, and in vitro experiments were employed to elucidate the potential roles and mechanisms of Astragalus root in the management of T2DM-NAFLD comorbidity. Results: A total of 25 bioactive constituents and 152 corresponding targets associated with Astragalus root were identified. PPI network analysis revealed the top ten core candidate targets, among which six possessed suitable crystal structures for molecular docking, including interleukin-6 (IL-6), threonine-protein kinase 1(AKT1), transcription factor AP-1(JUN), tumor necrosis factor (TNF), cysteine-dependent aspartate-specific protease 3 (CASP3), and estrogen Receptor 1(ESR1). Kyoto encyclopedia of genes and genomes (KEGG) analysis further identified the phosphatidylinositol 3-kinase (PI3K)-AKT as the most significantly enriched pathway. Molecular docking validated the potential binding modes of formononetin to the six core targets, a finding that was further confirmed by molecular dynamics simulations, which proved the stability of the resulting complexes. In vitro experiments demonstrated that formononetin obviously decreased lipid droplet accumulation, downregulated total cholesterol (TC) and triglyceride (TG) levels, suppressed the expression of TNF-α, IL-6, and interleukin-1β (IL-1β), decreased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and enhanced glutathione (GSH) content and superoxide dismutase (SOD) activity. These therapeutic effects were achieved through inhibition of protein expression within the PI3K/AKT/mechanistic target of rapamycin (mTOR) signaling pathway. Conclusions: This study determined the potential therapeutic targets and underlying mechanisms of formononetin derived from Astragalus root in the T2DM-NAFLD management, thereby providing a scientific basis for its clinical application.