黄柏不同炮制品中生物碱类成分在肾小管上皮细胞中的摄入差异考察  

Difference of intake of alkaloids in renal tubular epithelial cells from different kinds of processed products of Phellodendri Chinensis Cortex

作　　者：葛修通 赵佳慧 任文静 周悦 张凡[1,2] GE Xiu-tong;ZHAO Jia-hui;REN Wen-jing;ZHOU Yue;ZHANG Fan(College of Pharmacy,Liaoning University of Traditional Chinese Medicine,Dalian 116000,China;Liaoning TCM Processing Technology Innovation Center,Dalian 116000,China)

机构地区：[1]辽宁中医药大学药学院,辽宁大连116000 [2]辽宁省中药炮制专业技术创新中心,辽宁大连116000

出　　处：《中草药》2023年第18期5993-6000,共8页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学青年基金资助项目(81903801);辽宁省自然科学基金面上项目(2022-MS-287);沈阳市中青年科技创新人才项目(RC210192)。

摘　　要：目的探讨人肾小管上皮HK-2细胞摄取黄柏Phellodendri Chinensis Cortex中生物碱类成分的情况,以及HK-2细胞摄取黄柏中生物碱类成分的途径,从细胞层面验证黄柏“盐炙入肾”理论。方法利用UPLC-QqQ-MS技术分析HK-2细胞摄取生黄柏、盐黄柏和酒黄柏中的黄柏碱、木兰花碱、药根碱、小檗红碱和小檗碱5种成分差异,黄柏及其炮制品中5种生物碱类成分随着给药时间的含量变化;以及分析有机阴离子转运蛋白(organic anion transporters,OATs)抑制剂丙磺舒和有机阳离子转运蛋白(organic cation transporters,OCTs)抑制剂四乙基氯化铵对HK-2细胞摄取黄柏及其炮制品中5种生物碱类成分的影响。结果HK-2细胞对黄柏不同炮制品摄取差异表现为盐黄柏组>生黄柏组>酒黄柏组。抑制剂组HK-2细胞摄取差异主要表现为丙磺舒(OATs抑制剂)组>四乙氯化基铵(OCTs抑制剂)组。结论黄柏中生物碱成分可以被HK-2细胞摄取,其转运机制主要是OCTs介导的结果。盐炙品生物碱摄取较高,可能是盐炙提高了肾脏摄取型转运蛋白的活性。Objective To investigate the uptake of alkaloids from Huangbo(Phellodendri Chinensis Cortex)by human renal tubular epithelial HK-2 cells and the pathway of alkaloid uptake by HK-2 cells,so as to verify the theory of“entering into kidney through salt-water processing”from Phellodendri Chinensis Cortex at the cellular level.Methods UPLC-QqQ-MS technique was used to analyze the differences of phellodendrine,magnoflorine,jatrorrhizine,berberrubine and berberine uptake by HK-2 cells in raw Phellodendri Chinensis Cortex,salt-water processed of Phellodendri Chinensis Cortex and wine processed of Phellodendri Chinensis Cortex.The contents of five alkaloids in Phellodendri Chinensis Cortex and its processed products changed with the time of administration.The effects of organic anion transportors(organic anion transporters,OATs)inhibitor probenecid and organic cationic transportors(organic cation transporters,OCTs)inhibitor tetraethyl ammonium chloride on uptake of five alkaloids from Phellodendri Chinensis Cortex and its processed products by HK-2 cells were analyzed.Results The difference of HK-2 cell uptake of different processed products of Phellodendri Chinensis Cortex was as follows:salt-water processed group>raw group>wine processed group.The difference in uptake of HK-2 cells in the inhibitor group was mainly manifested as that of the probenecid(OATs inhibitor)group>tetraethyl ammonium chloride(OCTs inhibitor)group.Conclusion The alkaloids in Phellodendri Chinensis Cortex can be taken up by HK-2 cells,and their transport mechanism is mainly mediated by OCTs.The higher intake of alkaloids in salt-water processed group may be due to the increased activity of kidney uptake transporters.

关 键 词：黄柏 盐炙 肾小管上皮细胞 UPLC-QqQ-MS 黄柏碱 木兰花碱 药根碱 小檗红碱 小檗碱 有机阴离子转运蛋白 有机阳离子转运蛋白 

分 类 号：R285.61[医药卫生—中药学]