A Network Pharmacology-Based Approach for Exploring Key Active Compounds and Pharmacological Mechanisms of Tangshen Formula for Treatment of Diabetic Nephropathy

Abstract

Diabetic nephropathy (DN) is one of the common and severe microvascular complications of diabetes mellitus (DM). The occurrence and development of DN are related to multiple factors in the human body, which makes DN a complex disease, and the pathogeneses of DN have not yet been fully illustrated. Furthermore, DN lacks effective drugs for treatment nowadays. Chinese herbal medicine (CHM) often shows the feature of multicomponents, multitargets, multipathways, and synergistic effects and shows a promising source of new therapeutic drugs for DN. As a CHM, Tangshen Formula (TSF) was used to treat DN patients in China. However, its bioactive compounds and holistic pharmacological mechanisms on DN are both unclear. A network pharmacology approach was firstly applied to explore multiple active compounds and multiple key pharmacological mechanisms for TSF treating DN by drug-targeted interaction databases, herb-compound-target network, protein-protein interaction network, compound-target-pathway network, and analysis methods. And the results showed that TSF have the characteristic of multicomponents, multitargets, multipathways, and synergistic effects for treating DN. The quercetin, naringenin, kaempferol, and isorhamnetin as key active compounds and the PI3K-Akt signaling pathway, TNF signaling pathway, nonalcoholic fatty liver disease (NAFLD), focal adhesion, rap1 signaling pathway, T cell receptor signaling pathway, MAPK signaling pathway, and insulin resistance as the key molecular mechanisms play important roles in TSF treating DN. Moreover, quercetin, naringenin, kaempferol, and isorhamnetin were successfully detected in TSF by the UHPLC-MS/MS analysis method. And their concentrations were 0.224, 8.295, 0.0564, and 0.0879 mg·kg-1, respectively. The present findings not only provide new insights for a deeper understanding of the constituent basis and pharmacology of TSF but also provide guidance for further pharmacological studies on TSF.

Evidential support for garlic supplements against diabetic kidney disease: a preclinical meta-analysis and systematic review

“…The scores for included studies ranged from 2 to 6. Only one study got 2 points (4.17%), 74 4 studies got 3 points (20.83%), 58,60,68,69,81 14 studies got 4 points (58.33%), 59,61,66,67,70,72,73,75,77–80,82,84 3 studies got 5 points (12.5%), 62,76,83 and 1 study got 6 points (4.17%). 71 Only one study divided experimental animals into groups using a random number table, 71 while one study was assigned according to the results of body weight; 73 the information concerning this procedure was not mentioned in the remaining research.…”

“…Eventually, this systematic review and meta-analysis included 24 publications. 58–62,66–84 Over 70% of the literature was published within the previous ten years ( i.e. , 2012–2022), and the first of these included studies appeared in 2007, indicating that the great potential of garlic in the treatment of DKD is of increasing recent interest.…”

“…Since the housing conditions for animals were stated in 18 studies in all as being the same, we assumed that the animals were randomly housed during the experiment. 59–62,66,67,70,71,73,75–81,83,84 Two studies 60,81 performed random outcome assessment, but the specific randomized procedures were not reported. In terms of blinding of intervention measures and outcome evaluation, every study was unable to determine the precise risk.…”

Bioinformatics‐based and molecular docking study on the mechanism of action of Galla chinensis in the treatment of diabetic foot ulcers

“…Diabetic foot ulcers (DFUs) are the most common type of diabetes and one of the serious complications of diabetes, which can lead to amputation or even endanger patients' lives. DFU has a global prevalence of 6.3% 11–15 . Affecting 15% of diabetic patients, the treatment of DFU is still a challenge, the current treatment is still based on surgical debridement, and people suffering from diabetes endure the pain of long‐term lower limb ulcers 16–18 .…”

“…DFU has a global prevalence of 6.3%. [11][12][13][14][15] Affecting 15% of diabetic patients, the treatment of DFU is still a challenge, the current treatment is still based on surgical debridement, and people suffering from diabetes endure the pain of long-term lower limb ulcers. [16][17][18] Peripheral neuropathy and diabetic ulcers of the lower extremities are the main causes of hospitalization of patients.…”