Association and mechanism of Ligusticum chuanxiong alleviating itch: A combination of experimental and network pharmacology study

Ethnopharmacological relevance Ligusticum chuanxiong (CX) is a traditional Chinese medicine with diverse effects, such as anti-inflammatory, antioxidant, neuroprotective, anti-nociceptive, and anticancer properties. It has been used in clinical applications with satisfying therapeutic effects. However, the underlying mechanism that contributes to the anti-pruritic effects remains to be comprehensively investigated. Aim of the study The study aims to elucidate the effects and underlying molecular mechanisms of CX on alleviating the acute itch. Materials and methods Network pharmacology was conducted to identify protein-protein interactions and key therapeutic targets and pathways of CX on itch. The prediction results were verified by molecular docking and animal experiments, the acute itching mouse model was simulated by intradermal injection of histamine. The scratching behavior, c-Fos expression, and activation of GPER + neurons in the spinal cord were subsequently assessed and analyzed through behavioral testing and chemogenetic methodologies. Results A total of 7 bioactive components of CX could act on 72 itch potential targets, the GO analysis and the KEGG pathway were collected including hormone, membrane raft, transmembrane receptor, and estrogen signaling pathway. As illustrated in the molecular docking structure, the CX seven active monomers exhibited significant binding affinity towards three estrogen receptors. Animal experiments demonstrated that intraperitoneal administration of CX in a dose-dependent manner mitigated histamine-induced acute pruritus and concurrently elevated spinal c-Fos expression. CX substantially attenuates acute itch in acute chemical itching mice and suggests that CX inhibits itch information development and progression. GPER + neurons are more likely to play a role in the transmission of chemical itch. GPER + neurons may selectively contribute to acute itch, and CX inhibited the activation of GPER + neurons located in the spinal dorsal horn. Conclusions The study implies a potential positive association and mechanisms between CX and itch by combining network pharmacology and in vivo experiments. It is suggested that CX may offer a promising therapeutic application for patients suffering from itch, particularly in cases of severe itching.