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Clinical efficacies, underlying mechanisms and molecular targets of Chinese medicines for diabetic nephropathy treatment and management.
Acta Pharm Sin B. 2021 Sep; 11(9):2749-2767.AP

Abstract

Diabetic nephropathy (DN) has been recognized as a severe complication of diabetes mellitus and a dominant pathogeny of end-stage kidney disease, which causes serious health problems and great financial burden to human society worldwide. Conventional strategies, such as renin-angiotensin-aldosterone system blockade, blood glucose level control, and bodyweight reduction, may not achieve satisfactory outcomes in many clinical practices for DN management. Notably, due to the multi-target function, Chinese medicine possesses promising clinical benefits as primary or alternative therapies for DN treatment. Increasing studies have emphasized identifying bioactive compounds and molecular mechanisms of reno-protective effects of Chinese medicines. Signaling pathways involved in glucose/lipid metabolism regulation, antioxidation, anti-inflammation, anti-fibrosis, and podocyte protection have been identified as crucial mechanisms of action. Herein, we summarize the clinical efficacies of Chinese medicines and their bioactive components in treating and managing DN after reviewing the results demonstrated in clinical trials, systematic reviews, and meta-analyses, with a thorough discussion on the relative underlying mechanisms and molecular targets reported in animal and cellular experiments. We aim to provide comprehensive insights into the protective effects of Chinese medicines against DN.

Authors+Show Affiliations

School of Chinese Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR 999077, China.School of Chinese Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR 999077, China.School of Chinese Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR 999077, China.School of Chinese Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR 999077, China.School of Chinese Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR 999077, China.School of Chinese Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR 999077, China.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

34589395

Citation

Tang, Guoyi, et al. "Clinical Efficacies, Underlying Mechanisms and Molecular Targets of Chinese Medicines for Diabetic Nephropathy Treatment and Management." Acta Pharmaceutica Sinica. B, vol. 11, no. 9, 2021, pp. 2749-2767.
Tang G, Li S, Zhang C, et al. Clinical efficacies, underlying mechanisms and molecular targets of Chinese medicines for diabetic nephropathy treatment and management. Acta Pharm Sin B. 2021;11(9):2749-2767.
Tang, G., Li, S., Zhang, C., Chen, H., Wang, N., & Feng, Y. (2021). Clinical efficacies, underlying mechanisms and molecular targets of Chinese medicines for diabetic nephropathy treatment and management. Acta Pharmaceutica Sinica. B, 11(9), 2749-2767. https://doi.org/10.1016/j.apsb.2020.12.020
Tang G, et al. Clinical Efficacies, Underlying Mechanisms and Molecular Targets of Chinese Medicines for Diabetic Nephropathy Treatment and Management. Acta Pharm Sin B. 2021;11(9):2749-2767. PubMed PMID: 34589395.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical efficacies, underlying mechanisms and molecular targets of Chinese medicines for diabetic nephropathy treatment and management. AU - Tang,Guoyi, AU - Li,Sha, AU - Zhang,Cheng, AU - Chen,Haiyong, AU - Wang,Ning, AU - Feng,Yibin, Y1 - 2021/02/02/ PY - 2020/08/17/received PY - 2020/10/17/revised PY - 2020/12/25/accepted PY - 2021/9/30/entrez PY - 2021/10/1/pubmed PY - 2021/10/1/medline KW - ACEI, angiotensin-converting enzyme inhibitor KW - ADE, adverse event KW - AGEs, advanced glycation end-products KW - AM, mesangial area KW - AMPKα, adenosine monophosphate-activated protein kinase α KW - ARB, angiotensin receptor blocker KW - AREs, antioxidant response elements KW - ATK, protein kinase B KW - BAX, BCL-2-associated X protein KW - BCL-2, B-cell lymphoma 2 KW - BCL-XL, B-cell lymphoma-extra large KW - BMP-7, bone morphogenetic protein-7 KW - BUN, blood urea nitrogen KW - BW, body weight KW - C, control group KW - CCR, creatinine clearance rate KW - CD2AP, CD2-associated protein KW - CHOP, C/EBP homologous protein KW - CI, confidence interval KW - COL-I/IV, collagen I/IV KW - CRP, C-reactive protein KW - CTGF, connective tissue growth factor KW - Chinese medicine KW - D, duration KW - DAG, diacylglycerol KW - DG, glomerular diameter KW - DKD, diabetic kidney disease KW - DM, diabetes mellitus KW - DN, diabetic nephropathy KW - Diabetic kidney disease KW - Diabetic nephropathy KW - EMT, epithelial-to-mesenchymal transition KW - EP, E-prostanoid receptor KW - ER, endoplasmic reticulum KW - ESRD, end-stage renal disease KW - ET-1, endothelin-1 KW - ETAR, endothelium A receptor KW - FBG, fasting blood glucose KW - FN, fibronectin KW - GCK, glucokinase KW - GCLC, glutamate-cysteine ligase catalytic subunit KW - GFR, glomerular filtration rate KW - GLUT4, glucose transporter type 4 KW - GPX, glutathione peroxidase KW - GRB 10, growth factor receptor-bound protein 10 KW - GRP78, glucose-regulated protein 78 KW - GSK-3, glycogen synthase kinase 3 KW - Gαq, Gq protein alpha subunit KW - HDL-C, high density lipoprotein-cholesterol KW - HO-1, heme oxygenase-1 KW - HbA1c, glycosylated hemoglobin KW - Herbal medicine KW - ICAM-1, intercellular adhesion molecule-1 KW - IGF-1, insulin-like growth factor 1 KW - IGF-1R, insulin-like growth factor 1 receptor KW - IKK-β, IκB kinase β KW - IL-1β/6, interleukin 1β/6 KW - IR, insulin receptor KW - IRE-1α, inositol-requiring enzyme-1α KW - IRS, insulin receptor substrate KW - IκB-α, inhibitory protein α KW - JAK, Janus kinase KW - JNK, c-Jun N-terminal kinase KW - LC3, microtubule-associated protein light chain 3 KW - LDL, low-density lipoprotein KW - LDL-C, low density lipoprotein-cholesterol KW - LOX1, lectin-like oxidized LDL receptor 1 KW - MAPK, mitogen-activated protein kinase KW - MCP-1, monocyte chemotactic protein-1 KW - MD, mean difference KW - MDA, malondialdehyde KW - MMP-2, matrix metallopeptidase 2 KW - MYD88, myeloid differentiation primary response 88 KW - Molecular target KW - N/A, not applicable KW - N/O, not observed KW - N/R, not reported KW - NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells KW - NOX-4, nicotinamide adenine dinucleotide phosphate-oxidase-4 KW - NQO1, NAD(P)H:quinone oxidoreductase 1 KW - NRF2, nuclear factor erythroid 2-related factor 2 KW - OCP, oxidative carbonyl protein KW - ORP150, 150-kDa oxygen-regulated protein KW - P70S6K, 70-kDa ribosomal protein S6 kinase KW - PAI-1, plasminogen activator inhibitor-1 KW - PARP, poly(ADP-Ribose) polymerase KW - PBG, postprandial blood glucose KW - PERK, protein kinase RNA-like eukaryotic initiation factor 2A kinase KW - PGC-1α, peroxisome proliferator-activated receptor gamma coactivator 1α KW - PGE2, prostaglandin E2 KW - PI3K, phosphatidylinositol 3 kinases KW - PINK1, PTEN-induced putative kinase 1 KW - PKC, protein kinase C KW - PTEN, phosphatase and tensin homolog KW - RAGE, receptors of AGE KW - RASI, renin-angiotensin system inhibitor KW - RCT, randomized clinical trial KW - ROS, reactive oxygen species KW - SCr, serum creatinine KW - SD, standard deviation KW - SD-rat, Sprague–Dawley rat KW - SIRT1, sirtuin 1 KW - SMAD, small mothers against decapentaplegic KW - SMD, standard mean difference KW - SMURF-2, SMAD ubiquitination regulatory factor 2 KW - SOCS, suppressor of cytokine signaling proteins KW - SOD, superoxide dismutase KW - STAT, signal transducers and activators of transcription KW - STZ, streptozotocin KW - Signaling pathway KW - T, treatment group KW - TBARS, thiobarbituric acid-reactive substance KW - TC, total cholesterol KW - TCM, traditional Chinese medicine KW - TFEB, transcription factor EB KW - TG, triglyceride KW - TGBM, thickness of glomerular basement membrane KW - TGF-β, tumor growth factor β KW - TGFβR-I/II, TGF-β receptor I/II KW - TII, tubulointerstitial injury index KW - TLR-2/4, toll-like receptor 2/4 KW - TNF-α, tumor necrosis factor α KW - TRAF5, tumor-necrosis factor receptor-associated factor 5 KW - UACR, urinary albumin to creatinine ratio KW - UAER, urinary albumin excretion rate KW - UMA, urinary microalbumin KW - UP, urinary protein KW - VCAM-1, vascular cell adhesion molecule-1 KW - VEGF, vascular endothelial growth factor KW - WMD, weight mean difference KW - XBP-1, spliced X box-binding protein 1 KW - cAMP, cyclic adenosine monophosphate KW - eGFR, estimated GFR KW - eIF2α, eukaryotic initiation factor 2α KW - mTOR, mammalian target of rapamycin KW - p-IRS1, phospho-IRS1 KW - p62, sequestosome 1 protein KW - α-SMA, α smooth muscle actin SP - 2749 EP - 2767 JF - Acta pharmaceutica Sinica. B JO - Acta Pharm Sin B VL - 11 IS - 9 N2 - Diabetic nephropathy (DN) has been recognized as a severe complication of diabetes mellitus and a dominant pathogeny of end-stage kidney disease, which causes serious health problems and great financial burden to human society worldwide. Conventional strategies, such as renin-angiotensin-aldosterone system blockade, blood glucose level control, and bodyweight reduction, may not achieve satisfactory outcomes in many clinical practices for DN management. Notably, due to the multi-target function, Chinese medicine possesses promising clinical benefits as primary or alternative therapies for DN treatment. Increasing studies have emphasized identifying bioactive compounds and molecular mechanisms of reno-protective effects of Chinese medicines. Signaling pathways involved in glucose/lipid metabolism regulation, antioxidation, anti-inflammation, anti-fibrosis, and podocyte protection have been identified as crucial mechanisms of action. Herein, we summarize the clinical efficacies of Chinese medicines and their bioactive components in treating and managing DN after reviewing the results demonstrated in clinical trials, systematic reviews, and meta-analyses, with a thorough discussion on the relative underlying mechanisms and molecular targets reported in animal and cellular experiments. We aim to provide comprehensive insights into the protective effects of Chinese medicines against DN. SN - 2211-3835 UR - https://www.unboundmedicine.com/medline/citation/34589395/Clinical_efficacies_underlying_mechanisms_and_molecular_targets_of_Chinese_medicines_for_diabetic_nephropathy_treatment_and_management_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2211-3835(21)00002-2 DB - PRIME DP - Unbound Medicine ER -
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