Exploring the mechanism of Zanthoxylum bungeanum essential oil in alleviating acute pruritus in rats based on network pharmacology, molecular docking, and experimental pharmacology.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum bungeanum, as a crucial "dual-purpose resource for food and medicine", has been proven to possess a wide range of biological activities, including antimicrobial, anti-inflammatory, analgesic, and antioxidant effects. In the traditional application of Traditional Chinese Medicine, external use of Zanthoxylum bungeanum exhibits antipruritic efficacy and is commonly used to alleviate pruritus caused by eczema and mosquito bites. However, its underlying mechanism of action has not yet been systematically elucidated. AIM OF THE STUDY: This study aims to identify the compounds in Zanthoxylum bungeanum essential oil (ZO), preliminarily analyze the pathways and targets related to its alleviation of acute pruritus using network pharmacology and molecular docking, and verify the findings through in vivo experiments. MATERIALS AND METHODS: The compounds of ZO was analyzed using GC-MS. Pathways and targets related to acute pruritus were screened through databases including GenGards, OMIM, DrugBank, TTD, and Disgenet. Molecular docking was employed to examine the interactions between active compounds and potential targets. A rat model of acute pruritus was induced by subcutaneous injection of 5 mg/mL histamine phosphate solution into the nape of the neck. After 14 days of topical application of the test substance, behavioral observations were conducted; the levels of IL-4, IL-7,IgE, and IgM in serum were determined; and skin and spleen tissues were collected for pathological examination and detection of other relevant indicators. RESULTS: In total,21 compounds were identified from ZO. Among the identified compounds, linalool (81.60 %), 4-terpineol (3.18 %), D-limonene (3.12 %), and sabinene (3.07 %) being confirmed as the major bioactive constituents. Network pharmacology predicted that ZO alleviates acute itch potentially through targeting JAK1, STAT3, and STAT6, which was further supported by molecular docking simulations demonstrating strong binding affinity between these targets and the corresponding compounds. In vivo experiments revealed that ZO significantly alleviated acute itch in rats by: Downregulating serum levels of IL-4, IL-7, IgM, and IgG; Reducing CD3, CD4, and CD8T-cell populations in the spleen; Inhibiting phosphorylation of JAK1, STAT3, and STAT6 proteins in the skin. CONCLUSIONS: ZO demonstrated significant efficacy in alleviating acute itch in rats, It may alleviate skin pruritus in rats by down-regulating the levels of IL-4, IL-7, IgE, and IgM in serum, reducing the contents of CD3, CD4, and CD8in the spleen, inhibiting the expression of JAK1, STAT3, and STAT6 proteins, and weakening their immune capacity.