Affiliation:
1. Institute of Traditional Chinese Medicine & Natural Products College of Pharmacy Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research and International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China Jinan University Guangzhou P. R. China
2. College of Medicine Henan Engineering Research Center of Funiu Mountain's Medicinal Resources Utilization and Molecular Medicine Pingdingshan University Pingdingshan Henan P. R. China
3. PuraPharm Research Institute of PuraPharm(Nanning) Pharmaceutical Co. Ltd. Nanning P. R. China
4. R&D Centre of PuraPharm Corporation Ltd. Hong Kong SAR P. R. China
Abstract
An efficient strategy for the identification of potential nephroprotective substances in Zhu‐Ling decoction has been established with the integration of absorbed components characterization, pharmacokinetics, and activity evaluation. A qualitative method was developed to characterize the chemical constituents absorbed components in vivo of Zhu‐Ling decoction by using ultra‐performance liquid chromatography‐quadrupole‐time‐of‐flight mass spectrometry. A quantitative method was established and validated for the simultaneous determination of eight compounds in rat plasma by using ultra‐performance liquid chromatography‐triple quadruple tandem mass spectrometry. Finally, the nephroprotective activities of absorbed components with high exposure were assessed by cell survival rate, superoxide dismutase, and malondialdehyde activities in hydrogen peroxide–induced Vero cells. As a result, 111 compounds in Zhu‐Ling decoction and 36 absorbed components were identified in rat plasma and urine, and poricoic acid A, poricoic acid B, alisol A, 16‐oxo‐alisol A, and dehydro‐tumulosic acid had high exposure levels in rat plasma. Finally, poricoic acid B, poricoic acid A, 16‐oxo‐alisol A, and dehydro‐tumulosic acid showed remarkable nephroprotective activity against Vero cells damage induced by hydrogen peroxide. Besides, superoxide dismutase and malondialdehyde activities were obviously regulated in hydrogen peroxide–induced Vero cells by treatment with the four compounds mentioned above. Therefore, these four compounds were considered to be effective substances of Zhu‐Ling decoction due to their relatively high exposure in vivo and biological activity. This study provided a chemical basis for the action mechanism of Zhu‐Ling decoction in the treatment of chronic kidney diseases.
Subject
Filtration and Separation,Analytical Chemistry
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