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

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.

Malik S ，Suchal K ，Khan SI ，Bhatia J ，Kishore K ，Dinda AK ，Arya DS ... -  《-》

Anti-diabetic and renoprotective effects of aliskiren in streptozotocin-induced diabetic nephropathy in female rats.

Mahfoz AM ，El-Latif HA ，Ahmed LA ，Hassanein NM ，Shoka AA ... -  《-》

Renal-protective effect of thalidomide in streptozotocin-induced diabetic rats through anti-inflammatory pathway.

Zhang H ，Yang Y ，Wang Y ，Wang B ，Li R ... -  《Drug Design Development and Therapy》

Danshen injection ameliorates STZ-induced diabetic nephropathy in association with suppression of oxidative stress, pro-inflammatory factors and fibrosis.

Diabetic nephropathy (DN) is one of the most frequent complications in diabetes mellitus. This study aimed to explore whether Danshen injection is protective to renal tissue in diabetes. Intraperitoneal injection of streptozotocin (STZ) (60mg/kg) was used to induce diabetes in rats. Some STZ-induced diabetic rats were also intraperitoneally injected with Danshen solution at two different dosages (0.5 or 1ml/kg/day) for 6weeks. Our results showed that serum creatinine (sCr) and blood urea nitrogen were significantly increased in STZ-induced diabetic rats, which was alleviated upon Danshen injection. Danshen injection was also found to ameliorate hypertrophy and dilatation of renal tubule and glomeruli possibly by decreasing the expression of collagen and fibronectin in association with suppression of TGF-β1/Smad pathway. Further investigation revealed that Danshen injection could increase the activity of superoxide dismutase (SOD), and reduce reactive oxygen species (ROS) and malondialdehyde (MDA) levels in STZ-induced diabetic rats, indicating suppression of oxidative stress. In addition, we also found that Danshen injection could suppress IκB/NF-κB signaling pathway and reduce the level of a number of pro-inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the diabetic renal tissue, indicating suppression of inflammation. In conclusion, our results demonstrated that Danshen injection may rescue STZ-induced diabetic nephropathy, possibly via suppressing the oxidative stress, inflammatory responses and fibrosis progression.

Xu L ，Shen P ，Bi Y ，Chen J ，Xiao Z ，Zhang X ，Wang Z ... -  《-》

Renoprotective effect of Hypericum perforatum against diabetic nephropathy in rats: Insights in the underlying mechanisms.

Oxidative stress and inflammation play a key role in the initiation and progression of diabetic nephropathy (DN). The present study aimed to investigate the possible protective effect of hypericum perforatum (HP) against DN. Rats were allocated into six groups: control, received normal saline; diabetic untreated (DM), received single dose of streptozotocin (STZ) after injection of nicotinamide (NA); gliclazide, received STZ,NA + gliclazide (10 mg/kg); DM + HP50, DM + HP100, DM + HP200, received STZ,NA and HP 50, 100, 200 mg/kg, respectively. Gliclazide and HP were administered daily via gavage for 8 weeks. Serum glucose, insulin, kidney function and histopathological picture were assessed. Furthermore, oxidative/nitrosative stress, inflammatory cytokines, apoptotic and fibrotic markers were measured. Diabetic untreated group showed increase in serum glucose, urea, creatinine with albuminurea. Renal expression of protein for nuclear factor kappa-B (NF-кB), renal expression of inducible nitric oxide synthase (iNOS), cyclooxygenase II (COXII), collagen IV, fibronectin were elevated. Malondialdehyde (MDA), nitric oxide (NO), tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), intracellular adhesion molecule (ICAM-1), monocellular chemoattractant protein-1 (MCP-1), tumour growth factor- β (TGF-β), caspase-3 and cytochrome c contents were also increased consequently with decline of serum insulin, expression of peroxisome proliferator-activated receptor (PPARγ), renal reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Treatment with either gliclazide or HP mitigated the deleterious effects of STZ on the tested parameters. These findings indicate for the first time that HP may have a renoprotective effect against DN through reduction of oxidative/nitrosative stress, enhancement of antioxidant defense mechanisms, decline of inflammatory cytokines, antifibrotic, antiapoptotic and blood glucose lowering properties.

Abd El Motteleb DM ，Abd El Aleem DI 《-》