Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
1.
J Ethnopharmacol ; 293: 115283, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35427726

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Purendan (PRD), as a Chinese medicinal formula, behaves remarkable therapeutic effects on diabetes and complications in clinical and experimental research. However, the underlying pharmacological mechanism in the treatment of diabetic nephropathy (DN) is still unclear. AIMS: To investigate the therapeutical effects of PRD on DN and to explore its pharmacological mechanisms using network pharmacology and experimental verification. MATERIALS AND METHODS: The active compounds and putative targets in PRD, and disease-related targets of DN were extracted from public databases. The key targets were identified through the protein-protein interaction (PPI) network and module analysis. The GO and KEGG enrichment analysis were performed to discover potential pharmacological mechanisms. The expression of the key targets was detected in kidney tissue in Gene Expression Omnibus (GEO) dataset. The affinity between key proteins and corresponding compounds was evaluated by molecular docking and validated by the surface plasmon resonance (SPR) assay. The indicators on major pathways and hub genes were verified by in vivo experiments. RESULTS: In network pharmacology, 137 common targets in PRD for DN treatment were screened. The key targets and main signaling pathways including AGE-RAGE and lipid pathways were identified. The statistical difference in the expression of the key targets was verified in GSE96804 database, confirming the association with DN. The docking scores obtained from molecular docking illustrated good binding force between hub proteins and active compounds. And the good component-protein affinities were validated by SPR assay. Furthermore, the results of animal experiment indicated that PRD could ameliorate the level of serum glucose and renal function in rat model. It could regulate the expression of hub targets (AKT1, MAPK3, and STAT3) and improve indicators related with oxidative stress and lipid metabolism. CONCLUSION: The key targets and major signaling pathways in the treatment of PRD on DN were identified. The mechanism might relate to regulation of oxidative stress and lipid metabolism.

2.
Biomed Pharmacother ; 148: 112697, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35176709

ABSTRACT

Older people are more likely to develop insulin resistance and lipid metabolism disorders. Purendan (PRD) is a clinically verified traditional Chinese medicine compound, which plays an obvious role in regulating lipid metabolism disorder and improving insulin sensitivity. Our study aimed to investigate the efficacy and mechanism of PRD on aged type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD) rats. Sprague-Dawley rats (13 months) were fed with high-fat diet (HFD) and injected with low-dose STZ to replicate T2DM model. PRD was treated at three concentrations with metformin as a positive control. After administration, blood and liver tissue samples were collected to measure glucose metabolism indexes such as serum glucose and insulin, as well as lipid metabolism indexes such as TC, TG, LDL, HDL and FFA. Liver fat accumulation was observed by HE staining and oil red O staining. And protein expression levels of mTOR, p-mTOR, S6K1, p-S6K1 and SREBP-1c were detected by western blot. After PRD treatment, not only the insulin sensitivity and insulin resistance were significantly improved, but also the TC, TG, LDL, FFA, AST and ALT in serum and the lipid accumulation in liver tissue were significantly decreased. Moreover, PRD significantly down-regulated the expression of p-mTOR, p-S6K1 and SREBP-1c in liver tissues. In conclusion, PRD can alleviate NAFLD in aged T2DM rats by inhibiting the mTOR /S6K1/ SREBP-1c pathway.


Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Non-alcoholic Fatty Liver Disease , Aged , Animals , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Diet, High-Fat/adverse effects , Humans , Lipid Metabolism , Liver/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction , Sterol Regulatory Element Binding Protein 1/metabolism , TOR Serine-Threonine Kinases/metabolism
4.
Chin J Nat Med ; 18(8): 612-619, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32768168

ABSTRACT

Macroangiopathy is a complication of Type II Diabetes Mellitus (T2DM), which is mainly caused by fibrosis of blood vessels. Using T2DM rat models, we investigated whether the traditional Chinese medicine, Di-Dang Decoction (DDD), exhibited anti-fibrotic actions on great vessels. T2DM rats were randomly divided into non-intervention group, early-, middle-, late-stage DDD intervention groups and control groups, including pioglitazone group and aminoguanidine group. After administration of DDD to T2DM rats at different times, we detected the amount of extracellular matrix (ECM) deposition in the thoracic aorta. The results showed that early-stage intervention with DDD could effectively protect great vessels from ECM deposition. Considering that TGF-ß1 is the master regulator of fibrosis, we further validated at the molecular level that, compared to middle- and late-stage intervention with DDD, early-stage intervention with DDD could significantly decrease the expression levels of factors related to the activated TGF-ß1/Smad signalling pathway, as well as the expression levels of downstream effectors including CTGF, MMP and TIMP family proteins, which were directly involved in ECM remodelling. Therefore, early-stage intervention with DDD can reduce macrovascular fibrosis and prevent diabetic macroangiopathy.


Subject(s)
Diabetes Complications/prevention & control , Drugs, Chinese Herbal/therapeutic use , Fibrosis/prevention & control , Signal Transduction/drug effects , Vascular Diseases/prevention & control , Animals , China , Diabetes Mellitus, Experimental , Male , Rats , Rats, Sprague-Dawley , Smad Proteins/metabolism , Transforming Growth Factor beta1/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL