Clinical efficacies, underlying mechanisms and molecular targets of Chinese medicines for diabetic nephropathy treatment and management

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.

Effects of Tang Shen 2 Hao Fang, a Traditional Chinese Medicine, on Diabetic Nephropathy in Sprague–Dawley Rats

“…The results demonstrate that TS2HF was effective in the treatment of diabetic nephropathy in vivo when evaluated in rats with T2D nephropathy, similar to results of other TCM remedies. 10 These results are consistent with what is known about the effects of specific ingredients in the TS2HF mixture. According to traditional medicine theories, Astragalus mongholicus Bunge lowers blood glucose in type 1 and type 2 diabetes.…”

Bibliometric Study of Trends in the Diabetic Nephropathy Research Space from 2016 to 2020

“…As the onset of DN is often asymptomatic in its early stages, many diabetic patients exhibit proteinuria and, in some cases, nephrotic syndrome [ 13 ], with a subset of these patients ultimately developing ESRD and requiring dialysis. DN thus imposes a major medical and economic burden on affected patients, their families, and society as a whole [ 5 ]. However, research efforts pertaining to DN are complex and multifaceted, necessitating a comprehensive systematic overview of this research space in order to effectively identify current trends and emerging hotspots in the field.…”

“…The pathogenesis of DN is characterized by basement membrane thickening and glomerular extracellular matrix accumulation [ 3 ], with proteinuria serving as one of the earliest clinical signs of this disease prior to its progression to ESRD [ 4 ]. To date, traditional diabetes-related therapies such as weight loss, glycemic control, and renin-angiotensin-aldosterone system (RAAS) inhibitor administration have failed to yield satisfactory clinical outcomes as a means of treating DN [ 5 ].…”

Ginsenoside compound K inhibits obesity-induced insulin resistance by regulation of macrophage recruitment and polarization via activating PPARγ

“…28,29 For instance, TNF-α is a mononuclear macrophage pro-inflammatory factor, which is the earliest inflammatory factor to appear during the inflammatory response of the organism and it is elevated in patients with abnormal glucose tolerance. 30 Studies have shown that TNF-α also reduces the DNA binding activity of PPARγ, thereby inhibiting the expression of adiponectin mRNA, which in turn affects insulin signaling. 31 Our experimental results showed that prolonged feeding of the high-fat diet led to an expansion of adipocytes with severe inflammatory infiltration and significant positive expression of macrophage factors such as CD68 and CD11c in line with the literature description.…”