Apigenin ameliorates streptozotocin-induced diabetic nephropathy in rats via MAPK-NF-κB-TNF-α and TGF-β1-MAPK-fibronectin pathways.

Abstract

Diabetic nephropathy (DN), a microvascular complication of diabetes, has emerged as an important health problem worldwide. There is strong evidence to suggest that oxidative stress, inflammation, and fibrosis play a pivotal role in the progression of DN. Apigenin has been shown to possess antioxidant, anti-inflammatory, antiapoptotic, antifibrotic, as well as antidiabetic properties. Hence, we evaluated whether apigenin halts the development and progression of DN in streptozotocin (STZ)-induced diabetic rats. Male albino Wistar rats were divided into control, diabetic control, and apigenin treatment groups (5-20 mg/kg po, respectively), apigenin per se (20 mg/kg po), and ramipril treatment group (2 mg/kg po). A single injection of STZ (55 mg/kg ip) was administered to all of the groups except control and per se groups to induce type 1 diabetes mellitus. Rats with fasting blood glucose >250 mg/dl were included in the study and randomized to different groups. Thereafter, the protocol was continued for 8 mo in all of the groups. Apigenin (20 mg/kg) treatment attenuated renal dysfunction, oxidative stress, and fibrosis (decreased transforming growth factor-β1, fibronectin, and type IV collagen) in the diabetic rats. It also significantly prevented MAPK activation, which inhibited inflammation (reduced TNF-α, IL-6, and NF-κB expression) and apoptosis (increased expression of Bcl-2 and decreased Bax and caspase-3). Furthermore, histopathological examination demonstrated reduced inflammation, collagen deposition, and glomerulosclerosis in the renal tissue. In addition, all of these changes were comparable with those produced by ramipril. Hence, apigenin ameliorated renal damage due to DN by suppressing oxidative stress and fibrosis and by inhibiting MAPK pathway.

• Authors: Salma Malik, Kapil Suchal, Sana Irfan Khan, Jagriti Bhatia, Kamal Kishore, Amit Kumar Dinda, Dharamvir Singh Arya
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 313 Issue 2 Pg. F414-F422 (Aug 01 2017) ISSN: 1522-1466 [Electronic] United States
• PMID: 28566504 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2017 the American Physiological Society.

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Anti-Inflammatory Agents
• Antioxidants
• Apoptosis Regulatory Proteins
• Collagen Type IV
• Fibronectins
• Inflammation Mediators
• NF-kappa B
• Tgfb1 protein, rat
• Transforming Growth Factor beta1
• Tumor Necrosis Factor-alpha
• Streptozocin
• Apigenin
• Mitogen-Activated Protein Kinases
• Ramipril

Topics

• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Apigenin (pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Collagen Type IV (metabolism)
• Diabetes Mellitus, Experimental (chemically induced, drug therapy, enzymology, pathology)
• Diabetes Mellitus, Type 1 (chemically induced, drug therapy, enzymology, pathology)
• Diabetic Nephropathies (chemically induced, enzymology, pathology, prevention & control)
• Fibronectins (metabolism)
• Fibrosis
• Inflammation Mediators (metabolism)
• Kidney (drug effects, enzymology, pathology)
• Male
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• Oxidative Stress (drug effects)
• Ramipril (pharmacology)
• Rats, Wistar
• Signal Transduction (drug effects)
• Streptozocin
• Transforming Growth Factor beta1 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)