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在炎性瘙痒和疼痛小鼠模型中,研究槐果碱抑制瞬时受体电位(TRP)通道的抗炎、止痒和镇痛作用。

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

作者信息

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

机构信息

State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, College of Pharmacy, Jinan University, Guangzhou, Guangdong, 510632, China.

State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, College of Pharmacy, Jinan University, Guangzhou, Guangdong, 510632, China.

出版信息

J Ethnopharmacol. 2025 Jan 30;337(Pt 2):118882. doi: 10.1016/j.jep.2024.118882. Epub 2024 Oct 2.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Sophocarpine 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 STUDY

We 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 METHODS

We 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.

RESULTS

We 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.

CONCLUSIONS

Sophocarpine 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.

摘要

民族药理学相关性

槐果碱是从苦参干燥根中提取的一种生物活性化合物,苦参这种植物已被用于治疗包括皮肤瘙痒和疼痛在内的各种病症长达数千年。其止痒和镇痛作用在出版物中有所提及,但其与瞬时受体电位(TRP)通道相互作用的分子机制尚不清楚。

研究目的

我们在小鼠炎症性瘙痒和疼痛模型中研究了槐果碱的抗炎、止痒和镇痛作用,以阐明其潜在机制。

材料与方法

我们通过监测小鼠的搔抓和擦拭行为来评估槐果碱的止痒和镇痛作用,并通过测量银屑病面积和严重程度指数(PASI)评分来评估其抗炎作用。通过实时定量聚合酶链反应和蛋白质印迹法分析TRPA1/TRPV1的mRNA和蛋白表达。我们进一步研究了在给予异硫氰酸烯丙酯(AITC)或辣椒素的小鼠中槐果碱与TRPA1/TRPV1之间的关系,并进行了分子对接。

结果

我们发现槐果碱减少了搔抓发作、擦拭次数以及PASI评分,降低了皮肤中的肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)以及三叉神经节中的TRPA1和TRPV1。槐果碱预处理减少了AITC诱导的搔抓发作和擦拭次数以及辣椒素诱导的擦拭次数。我们还发现槐果碱与AITC/辣椒素之间对TRPA1/TRPV1存在潜在的竞争性结合。

结论

槐果碱是TRPA1和TRPV1通道的潜在竞争性抑制剂,具有强大的抗炎、止痒和镇痛作用,表明其在治疗炎症性瘙痒和疼痛疾病方面具有显著的治疗潜力。

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