Atopic dermatitis (AD), characterized by eczema as a chronic pruritic inflammatory skin disease, has become a serious health problem with recurrent clinical episodes. However, current clinical treatments have limited relief and are accompanied by adverse effects. Therefore, there is a necessity to develop new effective drugs for AD treatment. Angelica Yinzi (AYZ) is a classic ancient prescription for nourishing blood, moistening dryness, dispelling wind, and relieving itching. However, its mechanism for alleviating atopic dermatitis remains unknown. Therefore, this study aimed at determining the effects of AYZ and its potential mechanism in alleviating AD-like symptoms. In the present study, we used 1-chloro-2,4-dinitrobenzene (DNCB) to establish a mouse model of atopic dermatitis, where DNCB readily penetrates the epidermis to cause inflammation. Histopathological analysis was performed to examine the thickening of dorsal skin and infiltration in the inflammatory and mast cells in C57BL/6 mice. Additionally, the immunoglobulin E (IgE) levels in serum were determined by enzyme-linked immunosorbent assay (ELISA) kits. The IL-1β and TNF-α expression were detected using qRT-PCR. Next, the Western blotting and immunohistochemistry assays were performed to assess the contribution of MAPKs/NF-κB signaling pathways and the NLRP3 inflammasome in AD responses. Histopathological examination revealed that AYZ reduced the epidermal thickness of AD-like lesioned skin and repressed the infiltration of mast cells into AD-like lesioned skin. AYZ significantly decreased the phosphorylation of p38 MAPK, JNK, ERK and NF-κB and downregulated serum IgE levels and IL-1β and TNF-α mRNA levels. Additionally, the NLRP3, ASC, Caspase-1, and IL-1β expression in dorsal skin were effectively down-regulated following AYZ treatment (p < 0.05 and p < 0.01). These findings revealed that AYZ effectively suppressed AD-induced skin inflammation by inhibiting the activation of the NLRP3 inflammasome and the MAPKs/NF-kB signaling. Therefore, AYZ is a potential therapeutic agent against AD in the clinical setting.

Background: Pruritus ani (PA), a neurofunctional dermatosis, is one of the most common complications of hemorrhoids, which seriously affects the quality of life of patients. Medical hemorrhoid gel (MHG), a product mainly composed of herbal medicine, is widely used for treatment of PA clinically. This study aim to assess the alleviating effect and mechanism of MHG on PA based on rectal epidermis-spinal cord-brain axis using animal models.Methods: A chloroquine-induced mouse itching model and a croton oil preparation-induced rat hemorrhoid model were established to evaluate anti-PA effect of MHG. Scratching behaviors of mice were recorded, and histopathology of mice skin and rat ano-rectal tissues was observed through H&E staining. Network pharmacology and western blotting were employed to explore potential mechanism of MHG.Results: The study indicated that MHG significantly alleviated chloroquine-induced skin itching and improved pathological injuries in mice skin and rat ano-rectal tissues. Network pharmacology suggested that MHG might regulate the JAK/STAT signaling pathway. Experimental findings showed that MHG significantly downregulated TRPV1 and TRPA1 in rectal tissue, c-Fos and GRPR in spinal cord tissue, and 5-HT1a protein in brain tissue, while upregulating TRPM8 protein in rectal tissue. Furthermore, MHG inhibited the activation of the JAK2/STAT3 signaling pathway in the rectal epidermis-spinal cord-brain axis.Conclusion: MHG improves PA by inhibiting the transmission of itching signals in rectal epidermis-spinal cord-brain axis via the JAK2/STAT3 signaling pathway, providing experimental evidence for its clinical application.

Background: Hemorrhoidal disease (HD) is characterized by the pathological dilation of anal vascular cushions, causing pain, itching and bleeding. Recent evidence links HD onset and progression to rectal inflammation. Medical Hemorrhoid Gel (MHG), a multi-component botanical preparation, has gained empirical validation for HD management. This study aims to systematically evaluate the safety, efficacy, and mechanism of action of MHG in treating HD. Methods: The phytochemical composition of MHG was characterized using UPLC-QTOF-MS/MS and GC-MS/MS analyses. In vivo, the efficacy was assessed in a croton oil preparation (COP)‑induced HD rat model (n=10 per group) via anorectal coefficient (ARC) measurement, macroscopic severity score, Evans blue extravasation quantification, and H&E/PAS staining. Transcriptomic sequencing of anorectal tissues was integrated with experimental validation using ELISA, immunohistochemistry (IHC), and Western blotting to delineate molecular mechanism. Data were analyzed by one-way analysis of variance (ANOVA) followed by Dunnett’s multiple comparison post hoc test (significance at p< 0.05). Results: MHG significantly reduced ARC, macroscopic severity score, and Evans blue extravasation, restored intestinal villus structure and goblet cell numbers, and alleviated inflammation. Acute toxicity tests showed that MHG did not cause anorectal abnormalities or systemic toxicity in rats. Transcriptomic analysis integrated with experimental validation suggested the therapeutic mechanism of MHG involves inflammation response and NF-κB pathway. Specifically, MHG suppressed the levels of the pro-inflammatory mediator TNF-α, while it enhanced the levels of the anti-inflammatory mediator IL-10. Mechanistic studies revealed that MHG inhibited NLRP3 inflammasome activation, reduced the phosphorylation level of p65 and enhanced IκBα expression. Phytochemical analysis identified 20 constituents that contribute to the bioactivity of MHG. Conclusion: Our study substantiated that MHG exerts anti-hemorrhoidal effects through NLRP3 inflammasome suppression via NF-κB pathway regulation. This mechanistic insight provides scientific validation for clinical application of MHG in HD management.