Investigation of the anti-inflammatory, anti-pruritic, and analgesic effects of sophocarpine inhibiting TRP channels in a mouse model of inflammatory itch and pain

Article

作者: Zhou, Dan ; Nie, Hong ; Zeng, Hekun ; Verkhratsky, Alexei ; Zhang, Zhe ; Wang, Ranjing

ETHNOPHARMACOLOGICAL RELEVANCESophocarpine is a bioactive compound extracted from the dried root of Sophorae Flavesentis Aiton, a plant that has been used for thousands of years for various conditions including skin itch and pain. Its antipruritic and analgesic effects are suggested in publications, while the molecular mechanisms underneath interacting with TRP channels are not understood.AIM OF THE STUDYWe investigated the anti-inflammatory, antipruritic, and analgesic effects of sophocarpine in a murine inflammatory itch and pain model to elucidate the underlying mechanisms.MATERIALS AND METHODSWe evaluated sophocarpine's anti-pruritic and analgesic effects by monitoring mice's scratching and wiping behaviors, and the anti-inflammatory effect by measuring psoriasis area and severity index (PASI) score. The mRNA and protein expression of TRPA1/TRPV1 was analyzed by real-time quantitative polymerase chain reaction and western blotting. We further investigated the relationship between sophocarpine and TRPA1/TRPV1 in mice administered allyl-isothiocyanate (AITC) or capsaicin and by molecular docking.RESULTSWe found that sophocarpine decreased scratching bouts, wipes, and the PASI score, reduced the TNF-α and IL-1β in the skin and TRPA1 and TRPV1 in the trigeminal ganglion. Pretreatment of sophocarpine decreased AITC-induced scratching bouts and wipes and capsaicin-induced wipes. We also found potential competitive bindings between sophocarpine and AITC/capsaicin to TRPA1/TRPV1.CONCLUSIONSSophocarpine is a potential competitive inhibitor of TRPA1 and TRPV1 channels eliciting strong anti-inflammatory, anti-pruritic, and analgesic effects, suggesting its significant therapeutic potential in treating diseases with inflammatory itch and pain.

2024-11-06·Journal of Agricultural and Food Chemistry

Semi-Preparation and X-ray Single-Crystal Structures of Sophocarpine-Based Isoxazoline Derivatives and Their Pesticidal Effects and Toxicology Study

Article

作者: Chen, Lin ; Xu, Jianwei ; Lv, Min ; Xu, Hui ; Hao, Meng ; Wang, Yanyan ; Dou, Zihan ; Zuo, Sihui

Recently, research and development of novel pesticides from natural plant products have received much attention. To accelerate the application of sophocarpine as the agrochemical candidate, a series of novel sophocarpine-based isoxazoline derivatives were prepared by the 1,3-dipolar [2 + 3] cycloaddition reaction of sophocarpine with different chloroximes. Their structures were well characterized by high-resolution mass spectra, infrared spectra, and proton/carbon-13 nuclear magnetic resonance spectra. Eight steric configurations of compounds 5a, 5e', 5f, 5g, 5h, 5i, 5r, and 5u' were further determined by X-ray single-crystallography. Against Aphis citricola Van der Goot, compounds 5n (LD₅₀: 0.032 μg/nymph) and 5o (LD₅₀: 0.024 μg/nymph) exhibited greater than 3.7- and 4.9-fold potent aphicidal activity compared to sophocarpine (LD₅₀: 0.118 μg/nymph). Against Tetranychus cinnabarinus Boisduval, derivative 5g displayed the most promising acaricidal activity with the LC₅₀ value of 0.247 mg/mL, which was 14.2-fold that of sophocarpine. Compounds 5d and 5g also exhibited good control efficacy against T. cinnabarinus. Scanning electron microscopy images indicated that compound 5g can destroy the mite cuticle layer. These results will provide the foundation for the structural modification and use of sophocarpine derivatives as agrochemicals in the future.

2024-03-01·European Journal of Pharmacology

Sophocarpine alleviates intestinal fibrosis via inhibition of inflammation and fibroblast into myofibroblast transition by targeting the Sirt1/p65 signaling axis

Article

作者: Fang, Zihan ; Lai, Yueyang ; Li, Liu ; Tao, Lihuiping ; Fan, Minmin ; Shen, Weixing ; Cheng, Haibo ; Yu, Chengtao ; Jiang, Ruiyang ; Tan, Jiani ; Xu, Changliang ; Sun, Dongdong

In this study, we used alkaloids from Sophora flavescens to inhibit the SASP, leading to fibroblast-into-myofibroblast transition (FMT) to maintain intestinal mucosal homeostasis in vitro and in vivo. We used western blotting (WB) and immunofluorescence staining (IF) to assess whether five kinds of alkaloids inhibit the major inflammatory pathways and chose the most effective compound (sophocarpine; SPC) to ameliorate colorectal inflammation in a dextran sulfate sodium (DSS)-induced UC mouse model. IF, Immunohistochemistry staining (IHC), WB, disease activity index (DAI), and enzyme-linked immunosorbent assay (ELISA) were conducted to investigate the mechanism of action of this compound. Next, we detected the pharmacological activity of SPC on the senescence-associated secretory phenotypes (SASP) and FMT in interleukin 6 (IL-6)-induced senescence-like fibroblasts and discussed the mucosal protection ability of SPC on a fibroblast-epithelium/organoid coculture system and organ-on-chip system. Taken together, our results provide evidence that SPC alleviates the inflammatory response, improves intestinal fibrosis and maintains intestinal mucosal homeostasis in vivo. Meanwhile, SPC was able to prevent IL-6-induced SASP and FMT in fibroblasts, maintain the expression of TJ proteins, and inhibit inflammation and genomic stability of colonic mucosal epithelial cells by activating SIRT1 in vitro. In conclusion, SPC treatment attenuates intestinal fibrosis by regulating SIRT1/NF-κB p65 signaling, and it might be a promising therapeutic agent for inflammatory bowel disease.

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