Antioxidant and anti-inflammatory activities of Centratherum anthelminticum (L.) Kuntze seed oil in diabetic nephropathy via modulation of Nrf-2/HO-1 and NF-κB pathway.

BACKGROUND: Type 2 diabetes mellitus (T2DM) approximately constitutes 90% of the reported cases. 30-40% of diabetics eventually develop diabetic nephropathy (DN); accounting for one of the major causes of morbidity and mortality. Increased glucose autoxidation and non-enzymatic glycation of proteins in diabetic kidneys lead to the excessive generation of reactive oxygen species (ROS) that results in lipid peroxidation and activation of inflammatory mediators which overwhelms the scavenging capacity of the antioxidant defense system (Nrf2/Keap1/HO-1). Centratherum anthelminticum commonly called as kali zeeri (bitter cumin) and its seeds are well known for culinary purposes in Asia (Pakistan). It has reported anti-inflammatory, antioxidant, and anti-diabetic activities. The present study has attempted to explore the in-vivo anti-inflammatory, antioxidant and antihyperglycemic potential of the C. anthelminticum seed's fixed oil (FO) and its fractions in high fat-high fructose-streptozotocin (HF-HFr-STZ) induced T2DM rat model. METHODS: The T2DM rat model was developed by giving a high-fat and high-fructose diet followed by a single intraperitoneal injection of streptozotocin (STZ 60 mg/kg) on 28th day of the trial. After 72 hours of this injection, rats showing fasting blood glucose (FBG) levels≥230 mg/dL were recruited into six groups. These groups were orally administered distilled water (1 mL/kg), Gliclazide (200 mg/kg), Centratherum anthelminticum seed (FO) and its hexane (HF), chloroform (CF) and ethanol (EF) soluble fractions (200 mg/kg each), respectively for 4 weeks (i.e. 28 days). Blood, serum, and kidney tissue samples of euthanized animals were used for biochemical, pro-inflammatory, and antioxidant markers (ELISA, qRT-PCR, and spectrophotometric assays) and histology, respectively. RESULTS: C. anthelminticum FO and its fractions reduced the lipid peroxidation, and improved the antioxidant parameters: enzymatic (SOD, CAT, and GPx), non-enzymatic (GSH), and mRNA expression of anti-inflammatory markers (Nrf-2, keap1, and HO-1). mRNA expression of inflammatory and apoptotic markers (TNF-α, IL-1ß, COX-1, NF-κB, Bax, and Bcl-2) were attenuated along with improved kidney architecture. CONCLUSION: C. anthelminticum can mitigate inflammation and oxidative stress in early DN. The anti-nephropathic effect can be attributed to its ability to down-regulate NF-κB and by bringing the Nrf-2 expression levels to near normal.

Protective role of Avena fatua against drug-induced liver toxicity.

The study was conducted to examine the protective potential of ethanol seed extract (ESEt) of Avena fatua (wild oats) against antituberculosis drug (ATD)-induced hepatotoxicity in rats. Four groups of rats (n=6) were used. Of which, three groups were given ATD (Rimstar 900mg/15kg) and divided them into hepatotoxic control (distilled water 1mL/kg), positive control (silymarin 200mg/kg) and test group (ESEt 800mg/kg). The fourth was the normal control group treated only with distilled water (1mL/kg). All treatments were orally administered in their respective groups for 26 days. On the 27thday, rats were decapitated. Body and liver weights were measured whereas serum and liver samples were collected for biochemical and histopathological assessments. The rats treated with silymarin and ESEt showed a significant decrease (p<0.05, 0.01& 0.0001) in liver enzymes including alanine & aspartate transaminases, gamma glutamyltranspeptidase and alkaline phosphatase. ESEt also improved total bilirubin (particularly indirect bilirubin), total protein, albumin and low density lipoprotein cholesterol levels in test group. The hepatoprotective ability of extract was also evident by histological study of liver tissues of the test group that showed normal architecture as compared to liver of ATD treated hepatotoxic control group displayed heterogeneous hepatocytes, inflamed central vein, fatty deposits, enlarged sinusoid, Kupffer's cells infiltration, hypertrophy and fibrosis. In conclusion, ESEt of A.fatua is hepatoprotective in nature which may be due to the presence of total phenols and flavonoids already reported from the seeds of this plant.

Therapeutic role of Rauwolfia serpentina in minimizing the risk of glycosylation and associated biomarkers in experimentally induced type 1 diabetic mice.

Present work investigates the effects of hydro-methanolic roots extract (HyMREt) of Rauwolfia serpentina in type 1 diabetic mice. Mice were divided into normal, diabetic, negative and positive controls (I-IV) and three test (HyMREt doses) groups (V-VII - 50, 100, &150mg/kg). Allocated treatment of each group was given orally for 14 days in overnight fasted state. Percent change in fasting blood glucose (FBG), body weights, body tissue weights, hepatic glycogen, total lipids, glycosylated hemoglobin (HbA1c), complete blood profile and antioxidant enzymes including catalase (CAT) and superoxide dismutase (SOD) were estimated. HyMREt doses produced meaningful (p<0.0001) reduction (-39 to -53%) in FBG. Hemoglobin (Hb) levels were raised, HbA1c were considerably decreased (4.5-3.77%) and glycosylation (HbA1c to Hb) ratio was expressively (p<0.0001) improved in test groups. Dose-wise improvement (p< 0.05) in total glycogen and decrement (p<0.05) in lipids were observed in livers of test groups. HyMREt significantly decreased (p<0.05) percent inhibition of SOD and CAT. HyMREt doses progressively (p<0.05) improved RBC and other hematological parameters while decrement was only noticed in leucocyte counts. Administration of test doses of HyMREt were significantly reduced the glycosylation, oxidative stress and anemia caused by alloxan intoxication in mice.

Presence of gallic acid and rutin improve the hepatoprotective strength of Withania coagulans.

Carbon tetrachloride (CCl4) is one of the chemicals used in industry reported to accelerate the risk of liver diseases in workers especially in developing countries, if it is not handled carefully. Therefore, the present study conducted to evaluate the liver protective and oxidative stress reducing activities of methanolic (MFEt) and aqueous methanolic fruits (AqMFEt) extracts of Withania coagulans against CCl4-induced liver damage in rats. These fruits extracts in oral doses of 800 mg/kg were found effective in their respective test groups in decreasing weight loss, maintaining hepatic membrane integrity, biosynthetic and conjugative abilities by improving liver and bile duct specific enzymes (alanine and aspartate transferases, alkaline phosphatase, γ-glutamyltranstransferase), total protein and bilirubin profiles, uric acid levels plus uplifting the efficacy of hepatic antioxidant enzymes and protein by minimizing lipid peroxidation. All these beneficial effects confirmed by observing normal anatomical features of liver tissues in test groups. Total phenolic compounds were found high in AqMFEt. Interestingly, for the first time, gallic acid and rutin are identified and quantified in these extracts and thought to improve hepatoprotective potential of W. coagulans.