ArticleThe Journal of biological chemistry2016
Effects of the Nrf2 Protein Modulator Salvianolic Acid A Alone or Combined with Metformin on Diabetes-associated Macrovascular and Renal Injury.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 60 citations in OpenAlex.
- Salvia miltiorrhiza (Danshen) and its extracts in the alternative treatment of diabetic nephropathy: mechanisms and clinical perspectives.Journal of natural medicines · 2026Review
- Mechanisms of salvianolic acids in kidney disease therapy: advances and perspectives.Frontiers in pharmacology · 2026Review
- Salvianolic Acids and Their Pharmacological Promise in Kidney Diseases: A Narrative Review.International journal of nephrology and renovascular disease · 2026Review
- NRF2 Dysregulation and Therapeutic Insights Across Chronic Kidney Diseases.International journal of molecular sciences · 2025Review
- Exploration of metformin-based drug combination for mitigating diabetes-associated atherosclerotic diseases.World journal of diabetes · 2025Article
- Mechanism of Jianpixiaoke Recipe in Treating Type 2 Diabetes Based on Network Pharmacology and Molecular Docking.International journal of endocrinology · 2025Article
- Cocoa and Carob Supplementation, Alone or in Combination with Metformin, Protects against Hepatorenal Injury in Zucker Diabetic Fatty Rats.Nutrients · 2024Article
- Pharmacological characterization of the antidiabetic drug metformin in atherosclerosis inhibition: A comprehensive insight.Immunity, inflammation and disease · 2024Review
- Targeting oxidative stress as a preventive and therapeutic approach for cardiovascular disease.Journal of translational medicine · 2023Review
- Salvianolic acids and its potential for cardio-protection against myocardial ischemic reperfusion injury in diabetes.Frontiers in endocrinology · 2023Review
- Salvianolic acid A promotes mitochondrial biogenesis and function via regulating the AMPK/PGC-1α signaling pathway in HUVECs.Experimental and therapeutic medicine · 2022Article
- The effects of metformin monotherapy and combination of metformin and glibenclamide therapy on the expression ofJournal of diabetes and metabolic disorders · 2022Article
- Antioxidant effects of astaxanthin and metformin combined therapy in type 2 diabetes mellitus patients: a randomized double-blind controlled clinical trial.Research in pharmaceutical sciences · 2022Article
- A Review on the Antidiabetic Properties ofFrontiers in pharmacology · 2022Review
- Baicalein pre-treatment alleviates hepatic ischemia/reperfusion injury in mice by regulating the Nrf2/ARE pathway.Experimental and therapeutic medicine · 2021Article
- Ginkgolide B‑induced AMPK pathway activation protects astrocytes by regulating endoplasmic reticulum stress, oxidative stress and energy metabolism induced by Aβ1‑42.Molecular medicine reports · 2021Article
- Pharmacotherapy against Oxidative Stress in Chronic Kidney Disease: Promising Small Molecule Natural Products Targeting Nrf2-HO-1 Signaling.Antioxidants (Basel, Switzerland) · 2021Review
- A combination of herbal compound (SPTC) along with exercise or metformin more efficiently alleviated diabetic complications through down-regulation of stress oxidative pathway upon activating Nrf2-Keap1 axis in AGE rich diet-induced type 2 diabetic mice.Nutrition & metabolism · 2021Article
- Antioxidant Therapy and Antioxidant-Related Bionanomaterials in Diabetic Wound Healing.Frontiers in bioengineering and biotechnology · 2021Review
- Unfolding Nrf2 in diabetes mellitus.Molecular biology reports · 2021Review
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Authors and funding
11 authors at 2 institutions in 1 country.
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Abstract
Nuclear factor E2-related factor 2 (Nrf2) is considered a promising target against diabetic complications such as cardiovascular diseases and diabetic nephropathy. Herein, we investigated the effects of a potential Nrf2 modulator, salvianolic acid A (SAA), which is a natural polyphenol, on diabetes-associated macrovascular and renal injuries in streptozotocin-induced diabetic mice. Given that lowering glucose is the first objective of diabetic patients, we also examined the effects of SAA combined with metformin (MET) on both complications. Our results showed that SAA significantly increased the macrovascular relaxation response to acetylcholine and sodium nitroprusside in diabetic mice. Interestingly, treatment with SAA alone only provided minor protection against renal injury, as reflected by minor improvements in impaired renal function and structure, despite significantly reduced oxidative stress observed in the diabetic kidney. We demonstrated that decreased oxidative stress and NF-κB p65 expression were associated with SAA-induced expression of Nrf2-responsive antioxidant enzymes heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase (quinone) 1 (NQO-1), and glutathione peroxidase-1 (GPx-1) in vivo or in vitro, which suggested that SAA was a potential Nrf2 modulator. More significantly, compared with treatment with either SAA or MET alone, we found that their combination provided further protection against the macrovascular and renal injury, which was at least partly due to therapeutic activation of both MET-mediated AMP-activated protein kinase and SAA-mediated Nrf2/antioxidant-response element pathways. These findings suggested that polyphenol Nrf2 modulators, especially combined with drugs activating AMP-activated protein kinase, including hypoglycemic drugs, are worthy of further investigation to combat diabetic complications.
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