Progress of Chinese Medicine in Regulating Altered Lipid Metabolism in Renal Fibrosis

Authors

  • Liang Ma Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi, China
  • Xiaoyong Yu Shaanxi Provincial Hospital of Chinese Medicine, Xi’an 710003, Shaanxi, China

DOI:

https://doi.org/10.53469/jcmp.2025.07(03).08

Keywords:

Renal fibrosis, Lipid metabolism, Lipoproteins, Fatty acid oxidation, Traditional Chinese medicine, Review

Abstract

Renal fibrosis leads to progressive impairment of renal structure and function, which is a common pathologic impairment. There are few interventions targeting the mechanisms of fibrosis that can delay renal decompensation in patients. This review highlights the potential “antibiotic” of lipid metabolism and lipoproteins in ameliorating renal fibrosis, some representative targets and several other metabolic modulators with anti-fibrotic effects in the kidney, as well as the roles of fatty acid oxidation, lipids, and lipoprotein synthesis and catabolism in the prophylactic treatment of fibrosis. We describe the effects of lipid abnormalities on renal fibrosis and the renal pathophysiological lesions caused by lipid abnormalities, summarize the enzymes, transporter proteins, and transcription factors that contribute to the dysregulation of lipid metabolism in renal fibrosis, and discuss their roles in renal fibrosis. We summarized the renal protective effects of TCM monomers and TCM combinations mediating the pathways related to lipid metabolism flocculation, and made a review of them, aiming to provide theoretical basis for the drug development, basic research and clinical application of TCM in the prevention and treatment of renal fibrosis.

References

Wynn, T.A. and T.R. Ramalingam, Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med, 2012. 18(7): p. 1028-40.

Mora, A.L., et al., Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease. Nat Rev Drug Discov, 2017. 16(11): p. 755-772.

Nastase, M.V., et al., Targeting renal fibrosis: Mechanisms and drug delivery systems. Adv Drug Deliv Rev, 2018. 129: p. 295-307.

Shihab, F.S., Do we have a pill for renal fibrosis? Clin J Am Soc Nephrol, 2007. 2(5): p. 876-8.

Hinz, B. and D. Lagares, Evasion of apoptosis by myofibroblasts: a hallmark of fibrotic diseases. Nat Rev Rheumatol, 2020. 16(1): p. 11-31.

Djudjaj, S. and P. Boor, Cellular and molecular mechanisms of kidney fibrosis. Mol Aspects Med, 2019. 65: p. 16-36.

Humphreys, B.D., Mechanisms of Renal Fibrosis. Annu Rev Physiol, 2018. 80: p. 309-326.

Hwang, S. and K.W. Chung, Targeting fatty acid metabolism for fibrotic disorders. Arch Pharm Res, 2021. 44(9-10): p. 839-856.

Palm, W. and J. Rodenfels, Understanding the role of lipids and lipoproteins in development. Development, 2020. 147(24).

Suganami, T., M. Tanaka and Y. Ogawa, Adipose tissue inflammation and ectopic lipid accumulation. Endocr J, 2012. 59(10): p. 849-57.

Lin, T.A., V.C. Wu and C.Y. Wang, Autophagy in Chronic Kidney Diseases. Cells, 2019. 8(1).

Herman-Edelstein, M., et al., Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy. J Lipid Res, 2014. 55(3): p. 561-72.

Su, K., et al., Liraglutide attenuates renal tubular ectopic lipid deposition in rats with diabetic nephropathy by inhibiting lipid synthesis and promoting lipolysis. Pharmacol Res, 2020. 156: p. 104778.

Gao, Z. and X. Chen, Fatty Acid β-Oxidation in Kidney Diseases: Perspectives on Pathophysiological Mechanisms and Therapeutic Opportunities. Front Pharmacol, 2022. 13: p. 805281.

Ung, C.Y., et al., Metabolic perturbations in fibrosis disease. Int J Biochem Cell Biol, 2021. 139: p. 106073.

Chung, K.W., et al., Impairment of PPARα and the Fatty Acid Oxidation Pathway Aggravates Renal Fibrosis during Aging. J Am Soc Nephrol, 2018. 29(4): p. 1223-1237.

Kang, H.M., et al., Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nat Med, 2015. 21(1): p. 37-46.

Michalik, L., et al., International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol Rev, 2006. 58(4): p. 726-41.

Piret, S.E., et al., Loss of proximal tubular transcription factor Krüppel-like factor 15 exacerbates kidney injury through loss of fatty acid oxidation. Kidney Int, 2021. 100(6): p. 1250-1267.

Frangogiannis, N., Transforming growth factor-β in tissue fibrosis. J Exp Med, 2020. 217(3): p. e20190103.

Chen, L., et al., Central role of dysregulation of TGF-β/Smad in CKD progression and potential targets of its treatment. Biomed Pharmacother, 2018. 101: p. 670-681.

Gu, Y.Y., et al., TGF-β in renal fibrosis: triumphs and challenges. Future Med Chem, 2020. 12(9): p. 853-866.

Sun, I.O. and L.O. Lerman, Urinary microRNA in kidney disease: utility and roles. Am J Physiol Renal Physiol, 2019. 316(5): p. F785-F793.

Chau, B. N., et al., MicroRNA-21 promotes fibrosis of the kidney by silencing metabolic pathways. Sci Transl Med, 2012. 4(121): p. 121ra18.

Chen, Y.Y., X.G. Chen and S. Zhang, Druggability of lipid metabolism modulation against renal fibrosis. Acta Pharmacol Sin, 2022. 43(3): p. 505-519.

Jiayi X, Huifang Z, Luqun L, et al. Pathogenic role of microrna-21 in lipid metabolism disorder to promote fibrotic lesions in renal tissues andtubular epithelial cels of diabetic rats through downregulation of ppar-al [J]. J Chin J Pathophysiol, 2021, 37(10): 1858-67.

Price, N.L., et al., Genetic deficiency or pharmacological inhibition of miR-33 protects from kidney fibrosis. JCI Insight, 2019. 4(22).

Rysz, J., et al., The Role and Function of HDL in Patients with Chronic Kidney Disease and the Risk of Cardiovascular Disease. Int J Mol Sci, 2020. 21(2).

Rampanelli, E., et al., Excessive dietary lipid intake provokes an acquired form of lysosomal lipid storage disease in the kidney. J Pathol, 2018. 246(4): p. 470-484.

Du XG and X.Z. Ruan, Lipid Metabolism Disorder and Renal Fibrosis. Adv Exp Med Biol, 2019. 1165: p. 525-541.

Gao, X., et al., Oxidized high-density lipoprotein impairs the function of human renal proximal tubule epithelial cells through CD36. Int J Mol Med, 2014. 34(2): p. 564-72.

Yuanlin P, Dehai Y. Mechanism underlying treatment of diabetic kidney disease using traditional Chinese medicine based on theory of Yin and Yang balance [J]. Journal of Traditional Chinese Medicine, 2018, 38(5): 797-802.

Zhu Q., et al., Research progress of Chinese medicine on renal fibrosis. Guangming Traditional Chinese Medicine, 2013. 28(01): p. 205-207.

Ma L., et al., An analysis of the turbid-toxin theory for the treatment of renal fibrosis in Chinese medicine. Journal of Gansu College of Traditional Chinese Medicine, 2011. 28(02): p. 23-24.

Huang S T, Ding S C, Xu G F. Traditional Chinese medicine combined with low-dose glucocorticoid for treating nephrotic syndrome: A case report [J]. Drug Combination Therapy, 2019, 2(1): 34-44.

Li, B., et al., Research progress of berberine in the treatment of diabetes mellitus and its complications. Journal of Hubei Institute of Science and Technology (Medical Edition), 2021. 35(05): p. 448-452.

Rong, Q., et al., Berberine Reduces Lipid Accumulation by Promoting Fatty Acid Oxidation in Renal Tubular Epithelial Cells of the Diabetic Kidney. Front Pharmacol, 2021. 12: p. 729384.

CHEN X M, TIAN L X, GUO S X. Research progress on chemical constituents and pharmacological effects of sclerotia of polyporus umbellatus (polyporaceae, basidiomycota) [J]. Mycosystema, 2017, 36(1): 35-47.

Zhao, Y.Y., et al., Bioactivity-directed isolation, identification of diuretic compounds from Polyporus umbellatus. J Ethnopharmacol, 2009. 126(1): p. 184-7.

Zhao, Y.Y., et al., Ergosta-4, 6, 8(14), 22-tetraen-3-one isolated from Polyporus umbellatus prevents early renal injury in aristolochic acid-induced nephropathy rats. J Pharm Pharmacol, 2011. 63(12): p. 1581-6.

Wang, Y.N., et al., Polyporus Umbellatus Protects Against Renal Fibrosis by Regulating Intrarenal Fatty Acyl Metabolites. Front Pharmacol, 2021. 12: p. 633566.

Xiao, Y., et al., Baicalin inhibits pressure overload-induced cardiac fibrosis through regulating AMPK/TGF-β/Smads signaling pathway. Arch Biochem Biophys, 2018. 640: p. 37-46.

Lu, J., et al., Baicalin alleviates radiation-induced epithelial-mesenchymal transition of primary type II alveolar epithelial cells via TGF-β and ERK/GSK3β signaling pathways. Biomed Pharmacother, 2017. 95: p. 1219-1224.

Zheng, X.P., et al., Kidney-targeted baicalin-lysozyme conjugate ameliorates renal fibrosis in rats with diabetic nephropathy induced by streptozotocin. BMC Nephrol, 2020. 21(1): p. 174.

Wang Y, Zhou M, YU R. Reevaluation of systematic evaluation of Tripterygium glycosides in the treatment of diabetic kidney disease [J]. China Pharmacy, 2023: 2915-2921.

Ai Wei et al., Overview of raffinose polyglucoside treatment for lipid metabolism disorders secondary to nephrotic syndrome. Straits Pharmacology, 2015. 27(07): p.128-129.

Zhang, F., et al., Nephroprotective and nephrotoxic effects of Rhubarb and their molecular mechanisms. Biomed Pharmacother, 2023. 160: p. 114297.

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Published

2025-03-28

How to Cite

Ma, L., & Yu, X. (2025). Progress of Chinese Medicine in Regulating Altered Lipid Metabolism in Renal Fibrosis. Journal of Contemporary Medical Practice, 7(3), 43–47. https://doi.org/10.53469/jcmp.2025.07(03).08