Treatment and management of primary and secondary kidney diseases based on Chinese medicine : the roles of renal herb formula and isochlorogenic acid A

Abstract

Abstract of Thesis Entitled Treatment and Management of Primary and Secondary Kidney Diseases Based on Chinese Medicine: The Roles of Renal Herb Formula and Isochlorogenic Acid A Submitted by Guoyi TANG for the degree of Doctor of Philosophy at The University of Hong Kong in December 2023

Background Renal herb formula (RHF) was self-designed based on traditional Chinese medicine theory and clinical practice for the treatment of kidney diseases. It was hypothesized that RHF may exert reno-protective effects against certain types of kidney diseases. Objective This study was conducted to preliminarily determine the chemical, stability, and safety profiles of RHF, to systematically evaluate the effects of RHF on anti-GBM nephritis, nephrotic syndrome, hypertensive nephropathy, diabetic nephropathy, and hyperuricemic nephropathy, to thoroughly investigate the mechanisms involved in the effects of RHF against hyperuricemic nephropathy, and to deeply explore the roles of isochlorogenic acid A in treating hyperuricemic nephropathy. Methodology The fingerprint, chemical composition, stability profile of RHF was established using ultra-performance liquid chromatography-diode-array detector. The potential in-vitro toxicity of RHF was tested on HK-2 and AML12 cells, while in-vivo toxicity was assessed on C57BL/6N mice. The effects of RHF against anti-GBM nephritis, nephrotic syndrome, hypertensive nephropathy, diabetic nephropathy, and hyperuricemic nephropathy were evaluated on corresponding mice models. After that, the underlying mechanisms involved in the reno-protective effects of RHF against hyperuricemic nephropathy, and the potential roles of isochlorogenic acid A in treating hyperuricemic nephropathy, were further investigated using in vivo and in vitro assays accompanied by proteomics plus bioinformatics analysis. Result Chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, isochlorogenic acid A – C were identified as the characteristic compounds of RHF. These compounds were stable in storage conditions. The in-vitro and in-vivo toxicities of RHF were quite low, thus indicating acceptable safety profiles. RHF exerted some positive effects against anti-GBM nephritis, diabetic nephropathy, and hyperuricemic nephropathy, but not nephrotic syndrome and hypertensive nephropathy. Mechanism studies revealed that RHF may protect against hyperuricemic nephropathy by inhibiting NF-κB-mediated inflammatory p-53-associated apoptotic pathways. Isochlorogenic acid A as main bioactive compound of RHF showed potent effects against hyperuricemic nephropathy in vivo and in vitro, which involved the upregulation of TOMM20 that may facilitate protein transportation into mitochondria and promote cell proliferation. Conclusion Taken together, it may be a promising approach for the treatment of primary and secondary kidney diseases using Chinese medicine formula RHF. In particular, RHF and the bioactive compound isochlorogenic acid A may serve as safe and efficient candidates for hyperuricemic nephropathy, owing the inhibitory effects on kidney inflammation and cell apoptosis. Keyword Kidney disease; anti-GBM nephritis; nephrotic syndrome; hypertensive nephropathy; diabetic nephropathy; hyperuricemic nephropathy; traditional Chinese medicine; medicinal herb; chlorogenic acid; isochlorogenic acid A

Total words of this abstract: 440