藏药独一味镇痛作用、有效成分和镇痛作用机制的研究

Lamiophlomis rotata (Benth.) Kudo, a Tibetan herbal painkiller, has been clinically used for the management of various pain states in China. Lamiophlomis rotata, along with its formulations of pills, capsules, has been listed in China Pharmacopoeia. Within its broad constituents, China Pharmacopoeia has listed shanzhiside methyl ester, 8-O-acetylshanzhiside methyl ester and luteolin as quality control ingredients for Lamiophlomis rotata and its formulations. This study aims to 1) systemically study the analgesic property and tolerance of Lamiophlomis rotata aqueous extract on experimental pain models of bone cancer pain, neuropathic pain, diabetic pain and CFA-induced arthritis pain, supporting clinical application of Lamiophlomis rotata as a painkiller for patients with chronic pain states, 2) indentify whether shanzhiside methyl ester and 8-O-acetylshanzhiside methyl ester are principle effective ingredients, 3) explore whether Lamiophlomis rotata produces analgesia through direct activation of spinal glucagon-like peptide-1 receptors (GLP-1Rs), which in turn induces β-endorphin release. This study, for the first time, systemically investigates the analgesic property, effective ingredients and the underling mechanism of Lamiophlomis rotata, and may have high impacts on academia and practical implications.

独一味系藏族习用药材，具有止血和镇痛等活性，在临床上用来治疗 多种疼痛，疗效确切，其药材、制剂和适应症已收录中国药典。独一味含有多种成分，山栀苷甲酯和8-O-乙酰山栀苷甲酯甲酯以及芦丁为独一味药材及其制剂的质量控制指标化合物。本项目旨在骨癌疼痛、神经源性疼痛、糖尿病疼痛和CFA关节炎疼痛等慢性疼痛动物模型上，系统地研究独一味水提物对慢性疼痛的特异性镇痛作用和 镇痛耐受性，以支持独一味临床长期治疗慢性疼痛疗效；阐明独一味的指标成分山栀苷甲酯和8-O-乙酰山栀苷甲酯为独一味镇痛的有效成分；并从分子、细胞水平（包括稳定表达人GLP-1受体的HEK293细胞）和在体水平上进一步证明独一味通过激动脊髓背角小胶质细胞上GLP-1受体及其后续β-endorphin释放而产生有效镇痛作用。本研究系首次系统地研究独一味镇痛作用、有效成分和作用机制，具有较高学术水平和实用意义。

独一味系藏族习用药材，具有止血和镇痛等活性，在临床上用来治疗 各种疼痛，疗效确切，其药材、制剂和适应症已收录中国药典。本项目在骨癌疼痛、神经源性疼痛、糖尿病疼痛和CFA关节炎疼痛等慢性疼痛动物模型上，系统地研究了独一味水提物对慢性疼痛的特异性镇痛作用和镇痛耐受性；阐明独一味的指标成分山栀苷甲酯和8-O-乙酰山栀苷甲酯为独一味镇痛的有效成分；并从分子、细胞水平（包括稳转人GLP-1受体的HEK293细胞）和整体水平上进一步证明独一味通过激动脊髓背角小胶质细胞上GLP-1受体及其后续β-endorphin释放而产生有效镇痛作用。