Hepatoprotective effect of taxifolin on cyclophosphamide-induced oxidative stress, inflammation, and apoptosis in mice: Involvement of Nrf2/HO-1 signaling

Taxifolin (TA) is a natural flavonoid found in many foods and medicinal plants with well-documented antioxidant and anti-inflammatory properties. Cyclophosphamide (CP) is an effective antineoplastic and immunosuppressive agent; however, it is associated with numerous adverse events, including hepatotoxicity. Herein, we aimed to investigate the potential protective effects of TA using a mouse model of CP-induced hepatotoxicity. Mice were co-treated with TA (25 and 50 mg/kg, orally) and CP (30 mg/kg, i.p.) for 10 consecutive days and sacrificed 24 hours later. CP induced increased transaminases (ALT and AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) paralleled with pronounced histopathological alterations in the liver. Moreover, hepatic tissues of CP-injected mice showed increased malondialdehyde (MDA), protein carbonyl, and nitric oxide (NO) levels, accompanied by decreased antioxidant defenses (glutathione [GSH], superoxide dismutase [SOD], and catalase [CAT]). Livers of CP-injected mice also showed increased inflammatory response (nuclear transcription factor kappa-B [NF-κB] p65 activation, increased levels of proinflammatory cytokines tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL-1β], and IL-6) and apoptosis (decreased Bcl-2 and increased Bax and caspase-3 expression levels). Remarkably, TA ameliorated markers of liver injury and histological damage in CP-injected mice. TA treatment also attenuated numerous markers of oxidative stress, inflammation, and apoptosis in the liver of CP-injected mice. This was accompanied by increased nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) expression in the liver tissues of CP-injected mice. Taken together, this study indicates that TA may represent a promising new avenue to prevent/treat CP-induced hepatotoxicity and perhaps other liver diseases associated with oxidative stress and inflammation

Antioxidant, Anti-Obesity, and Hypolipidemic Effects of Polyphenol Rich Star Anise (<i>Illicium verum</i>) Tea in High-Fat-Sugar Diet-Induced Obesity Rat Model

Star anise (Illicium verum Hook. fil.) is commonly utilized as a culinary and medicinal fruit and is most famous in indigenous systems of medicine. The present research work aims to appraise and validate the potential of polyphenol-rich star anise tea (SAT) on oxidative stress, obesity and related biochemical parameters in high-fat-sugar-diet (HFSD)-induced obesity model in rats. SAT was prepared using the traditional method in warm water. The Reverse Phase High Pressure Liquid Chromatography (RP-HPLC) analysis was performed for the simultaneous determination of phenolic acids and flavonoids in SAT. Two doses (250 and 500 mg/kg body weight) were selected to investigate the anti-obesity potential of SAT using HFSD-induced obese rat model. Major (>5 mg/100 mL) phenolic acids in SAT were p-coumeric acid, gallic aid, cinamic acid, chlorogenic acid and ferulic acid while catechin and rutin were the major flavonoids detected in the SAT. SAT exhibited 51.3% DPPH radical scavenging activity. In vivo study showed that higher doses of SAT (500 mg/kg body weight) significantly reduced the body weight increase (74.82%) and BMI (0.64 g/cm2). Moreover, significant reductions in the levels of serum total cholesterol, triglyceride, LDL and VLDL were recorded in all the treatment groups in comparison to the HFSDC group. Furthermore, SAT reduced the alterations in MDA, SOD and GSH levels of experimental groups thus showing the potential against oxidative stress. The SAT-500 group showed a significant decrease in the elevated kidney and liver weights and atherogenic index in comparison to the HFSDC group. The present study proved that SAT exhibited strong protective effects against obesity and oxidative stress, especially at higher doses

Cardioprotective Effect of Taxifolin against Isoproterenol-Induced Cardiac Injury through Decreasing Oxidative Stress, Inflammation, and Cell Death, and Activating Nrf2/HO-1 in Mice

Oxidative stress and inflammation are key components in cardiovascular diseases and heart dysfunction. Herein, we evaluated the protective effects of (+)-taxifolin (TAX), a potent flavonoid with significant antioxidant and anti-inflammatory actions, on myocardial oxidative tissue injury, inflammation, and cell death, using a mouse model of isoproterenol (ISO)-induced acute myocardial injury. Mice were given TAX (25 and 50 mg/kg, orally) for 14 days before receiving two subsequent injections of ISO (100 mg/kg, s.c.) at an interval of 24 h on the 15th and 16th days. The ISO-induced cardiac tissue injury was evidenced by increased serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), and lactate dehydrogenase (LDH), along with several histopathological changes. The ISO also induced increased malondialdehyde (MDA) with concomitant declined myocardial glutathione level and antioxidant enzymes activities. Moreover, ISO-induced heart injury was accompained with elevated cardiac NF-&kappa;B p65, TNF-&alpha;, IL-1&beta;, Bax, and caspase-3, as well as decreased Bcl-2, Nrf2, and HO-1. Remarkably, TAX reduced the severity of cardiac injury, oxidative stress, inflammation, and cell death, while enhancing antioxidants, Bcl-2, and Nrf2/HO-1 signaling in ISO-injected mice. In conclusion, TAX protects against ISO-induced acute myocardial injury via activating the Nrf2/HO-1 signaling pathway and attenuating the oxidative tissue injury and key regulators of inflammatory response and apoptosis. Thus, our findings imply that TAX may constitute a new cardioprotective therapy against acute MI, which undoubtedly deserves further exploration in upcoming human trials

Antioxidant, carbonic anhydrase inhibition and diuretic activity of Leptadenia pyrotechnica Forssk. Decne

Background: Leptadenia pyrotechnica Forssk. Decne is a member of family Apocynaceae and locally known as ‘Khipp’. It is found in dry, sandy habitat of Pakistan and in several other regions around the world including Asia, Tropical Africa, Western Gulf and Mediterranean countries. It has nutritional value, containing 4 % lipids, 23 % proteins, 28 % carbohydrates, 4 % fibers, vitamin E and several minerals. Traditionally, this plant has been used by several communities for pain, different inflammatory and kidney disorders. Ethno-botanical studies have reported the use of L. pyrotechnica in nephrolithiasis, kidney disorders and induction of diuresis, which requires a detailed pharmacological study to validate the folkloric use of L. pyrotechnica as diuretic. Methods: The 70 % methanolic L. pyrotechnica (Lp.Cr) extract was prepared and qualitatively checked for the presence of various phytochemicals. Phenolic, flavonoid, tannin and saponin contents were quantified. GC-MS analysis of Lp.Cr was also performed. Antioxidant potential of Lp.Cr was evaluated by DPPH, ABTS and nitrite radical scavenging assays. CUPRAC and FRAP assay described the reducing potential of Lp.Cr. Diuretic activity was performed in both acute and prolonged models at different doses followed by the estimation of electrolytes, urea and creatinine levels. The mechanism of diuresis was described by pre-treatment with atropine, l-NAME, indomethacin and carbonic anhydrase inhibition. Results: Lp.Cr. indicated high phenolic and flavonoid contents which correlated with good antioxidant activity. GC-MS analysis showed the presence of 104 compounds from different phytochemical classes. Diuretic activity was performed at 10–300 mg/kg concentrations where the dose of 100 and 300 mg/kg showed good diuretic and saluretic activity comparable to furosemide. Lp.Cr exhibited diuresis both in acute and prolonged study protocols which can be attributed to carbonic anhydrase inhibition, effect on prostaglandins and cholinergic pathways. Conclusion: L. pyrotechnica contained several phytochemicals and exhibited good antioxidant activity. It induced diuresis and saluretic activity which was comparable to furosemide at higher doses. Diuretic activity can be attributed to carbonic anhydrase inhibition, prostaglandin synthesis and cholinergic pathways

Betulin prevents high fat diet-induced non-alcoholic fatty liver disease by mitigating oxidative stress and upregulating Nrf2 and SIRT1 in rats

Non-alcoholic fatty liver disease (NAFLD) is a common chronic hepatic disorder characterized by hepatic lipid accumulation. This study explored the effect of betulin (BE), a terpenoid with promising antioxidant, anti-inflammatory and insulin sensitizing effects, on NAFLD induced by high fat diet (HFD). Rats received HFD and BE (15 and 30 mg/kg) for 12 weeks and blood and liver samples were collected for analyses. HFD caused hyperlipidemia, cholesterol and triglycerides accumulation in the liver, hepatocellular ballooning, fibrosis, insulin resistance (IR), lipid peroxidation (LPO), and NF-kB p65 upregulation. BE ameliorated serum and liver lipids, blood glucose and insulin, liver LPO, prevented steatosis and fibrosis, suppressed NF-kB p65 and enhanced antioxidants in HFD-fed rats. BE downregulated acetyl-CoA carboxylase (ACC1) and fatty acid synthase (FAS), and upregulated Nrf2, HO-1 and SIRT1 in the liver of HFD-fed rats. In silico investigations revealed the binding affinity of BE towards FAS, NF-kB, Keap1, HO-1 and SIRT1. In conclusion, BE attenuated HFD-induced NAFLD by ameliorating hyperlipidemia, IR, lipogenesis, liver lipid accumulation, and oxidative stress. The protective effect of BE was associated with enhanced Nrf2/HO-1 signaling and SIRT1