Sheikh Bilal Ahmad

Naringenin (4,5,7-trihydroxyflavanone) suppresses the development of precancerous lesions via controlling hyperproliferation and inflammation in the colon of Wistar rats

Colon cancer is a world‐wide health problem and one of the most dangerous type of cancer, affecting both men and women. Naringenin (4, 5, 7‐trihydroxyflavanone) is one of the major flavone glycoside present in citrus fruits. Naringenin has long been used in Chineses traditional medicine because of its exceptional pharmacological properties and non‐toxic nature. In the present study, we investigated the chemopreventive potential of Naringenin against 1,2‐dimethyhydrazine (DMH)‐induced precancerous lesions, that is, aberrant crypt foci (ACF) and mucin depleted foci (MDF), and its role in regulating the oxidative stress, inflammation and hyperproliferation, in the colon of Wistar rats. Animals were divided into five groups. In groups 3‐5, Naringenin was administered at the dose of 50 mg/kg b. wt. orally while in groups 2‐4, DMH was administered subcutaneously in the groin at the dose of 20 mg/kg b. wt. once a week for first 5 weeks and animals were euthanized after 10 weeks. Administration of Naringenin ameliorated the development of DMH‐induced lipid peroxidation, ROS formation, precancerous lesions (ACF and MDF) and it also reduced the infiltration of mast cells, suppressed the immunostaining of NF‐κB‐p65, COX‐2, i‐NOS PCNA and Ki 67 Naringenin treatment significantly attenuated the level of TNF‐α and it also prevented the depletion of the mucous layer. Our findings suggest that Naringenin has strong chemopreventive potential against DMH‐induced colon carcinogenesis but further studies are warranted to elucidate the precise mechanism of action of Naringenin.

Zingerone (4-(4-hydroxy-3-methylphenyl)butan-2-one) ameliorates renal function via controlling oxidative burst and inflammation in experimental diabetic nephropathy

Abstract Development of diabetic nephropathy (DN) is directly linked to oxidative stress and inflammation. In this context, inflammatory and oxidative markers have gained much attention as targets for therapeutic intervention. We studied the effect of zingerone in a streptozotocin/high fat diet (STZ/HFD)-induced type 2 diabetic Wistar rat model. Zingerone also known as vanillyl acetone is a pharmacologically active compound present usually in dry ginger. STZ/HFD caused excessive increase in ROS and inflammation in experimental animals. The treatment with zingerone markedly abrogated ROS levels, inhibited the NF-кB activation and considerably reduced level of other downstream inflammatory molecules (TNF-α, IL-6, IL-1β), furthermore, zingerone treatment improved renal functioning by significantly decreasing the levels of kidney toxicity markers KIM-1, BUN, creatinine, and LDH and suppressed TGF-β. Collectively, these findings indicate that zingerone treatment improved renal function by anti-hyperglycaemic, anti-oxidant, and anti-inflammatory effects, suggesting the efficacy of zingerone in the treatment of DN.

Zingerone (4-(4-hydroxy-3-methylphenyl) butan-2-one) protects against alloxan-induced diabetes via alleviation of oxidative stress and inflammation: Probable role of NF-kB activation

Diabetes is considered as the most common metabolic disease affecting millions of people all around the world. Use of natural herbal medicines can be effective in treating diabetes. Zingerone (4-(4-hydroxy-3-methylphenyl) butan-2-one) a polyphenolic alkanone extracted from ginger has a broad spectrum of pharmacological properties and thus can be used as a promising candidate against various ailments. In the current study we aimed at demonstrating the protective effect of zingerone against diabetes mellitus and elucidating its possible mechanism. Five groups of animals (I-V) were made with ten animals each. Group I (control) was given normal saline orally. Group II (diabetic positive control) was given alloxan at the dose rate of 100 mg/kg bwt once. Group III and IV was given alloxan once at the dose rate of 100 mg/kg bwt. and received oral treatment of zingerone at a dose rate of 50 and 100 mg/kg bwt respectively daily for 21 days. Group V was given alloxan at the dose of 100 mg/kg bwt. and was treated with standard drug glibenclamide at the dose rate of 4.5 mg/kg bwt. daily for 21 days. According to our findings we confirmed that zingerone restrained the alloxan induced oxidative stress by increasing the activity of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and reducing the peroxidative damage. We also confirmed that zingerone suppressed the level of redox sensitive transcription factor NFκB and downregulated other downstream inflammatory cytokines like interleukins (IL1-β IL-2, IL-6) and tumor necrosis factor alpha (TNF-α). Moreover, the experimental findings suggested that zingerone improved the insulin levels. Taken together our results indicated that zingerone effectively ameliorated the diabetes induced complications which provide a strong theoretical basis for zingerone to be used clinically for treatment of diabetes.

Antifibrotic effects of D-limonene (5(1-methyl-4-[1-methylethenyl]) cyclohexane) in CCl4 induced liver toxicity in Wistar rats

This study was designed to assess the potential antifibrotic effect of D‐Limonene—a component of volatile oils extracted from citrus plants. D‐limonene is reported to have numerous therapeutic properties. CCl4‐intduced model of liver fibrosis in Wistar rats is most widely used model to study chemopreventive studies. CCl4‐intoxication significantly increased serum aminotransferases and total cholesterol these effects were prevented by cotreatment with D‐Limonene. Also, CCl4‐intoxication caused depletion of glutathione and other antioxidant enzymes while D‐Limonene preserved them within normal values. Hydroxyproline and malondialdehyde content was increased markedly by CCl4 treatment while D‐Limonene prevented these alterations. Levels of TNF‐α, TGF‐β, and α‐SMA were also assessed; CCl4 increased the expression of α‐SMA, NF‐κB and other downstream inflammatory cascade while D‐Limonene co‐treatment inhibited them. Collectively these findings indicate that D‐Limonene possesses potent antifibrotic effect which may be attributed to its antioxidant and anti‐inflammatory properties.

Endocrine Disrupting Chemicals (EDCs) and Fish Health- A Brief Review

Health of an intact organism or its progeny depends on a proper-functioning of endocrine system to regulate the release of certain hormones that are essential for functions such as growth, metabolism, development, mood, sleep etc. Substances disrupting or interfering with normal hormonal balance and hence exerting adverse effects on health of an organism are known as Endocrine disrupting chemicals (EDCs). Principal toxic effects of EDCs were reported to be related to infertility, thyroid function disruption and teratogenicity, but other important toxic effects of EDCs such as carcinogenicity and mutagenicity have also been demonstrated. Large amounts of EDCs are found in aquatic environments from wastewater, industrial contamination and hospital runoffs. The exposure to EDCs to commercial and ecologically important marine and freshwater fish stocks has seriously affected their production. Current write up provides an assessment of recent investigations into endocrine disruption in fresh and aquatic life. We focused on natural or synthetic chemical compound in water that effect endocrine functioning in fishes.

Biochemical Profile and Genetic Polymorphism of MTHFRC677T in Risk of Type 2 Diabetes Mellituss

Diabetes mellitus (DM) is a common endocrine metabolic disorder and a leading cause of death worldwide Diabetes type-2 is a multicausal disease which develops slowly and in a stepwise order. Our study showed there was no significant difference in serum high density lipoprotein (HDL) and Tri glyceride (TG) of patients and controls (0.90±0.59 vs 1.15±0.39 p>0.05) and (1.19±0.70 vs 1.01±0.52 p>0.060) respectively. Low density lipoprotein (LDL) and total cholesterol (TC) are significantly higher in patients than control group (4.09±1.14 vs 3.01±1.02 p<0.0002) and (4.21±1.28 vs 3.78±1.29 p<0.05). However, HDL/TC ratio is significantly higher in patients than controls (0.21±0.91 vs 0.30±0.99 p<0.05). Serum levels of all liver enzymes (ALT, AST, and ALP) analyzed are significantly higher in patients than controls (12.69±10.80 vs 4.95±2.66, p<0.0002), (15.99±10.70 vs 6.95±3.84, p<0.0002) and 68.29±27.78 vs 21.27±7.77, p<0.0001) respectively. On genetic level the role of MTHFR C677T polymorphisms our results showed 63% of the cases showed homozygous mutant condition. The allelic association of polymorphism of controls with cases was found to be significant (P=0.007). Homozygous mutant condition of MTHFRC677T gene was found to be certainly higher in Diabetes Mellitus 2 Cases of above 60 years of age (80%), than ages below 60 years and in controls (16.6%) and was significant as p=0.005, compared to below 60 years of age (33.3%) and in controls (0%) and association was insignificant as p=0.4667. Our data suggest that there is an important role of LDL, TC, HDL/TC, ALT, AST, and ALP in type-2 Diabetes, also gene polymorphisms of MTHFR C677T gene may act synergistically to increase the risk of type 2 diabetes.

Ameliorative Effects of Vitamin C in Cholpyrifos Induced Toxicity in Snow Trout (Schizothorax niger)

The present study was carried out to investigate the ameliorative potential of vitamin C in chlorpyrifos induced toxicity in snow trout (Schizothorax niger). Forty healthy fishes were divided into 4 groups of ten fishes each. Group I was a normal control group (without chlorpyrifos and vitamin-C), group II was given chlorpyrifos at the dose of 0.075 mg/L without vitamin C, group III was exposed with chlorpyrifos at the dose of 0.075 mg/L and co treated with vitamin C (40 ppm) whereas group IV was exposed with chlorpyrifos at the dose of 0.075 mg/L and co treated with vitamin C (70 ppm). Treatment was continuously carried out for 41 days. Liver tissue homogenate was analyzed for antioxidant parameters. It was found that chlorpyrifos suppressed the antioxidant enzyme activity significantly and negatively affected the haematological parameters while supplementation with vitamin-C markedly improved the antioxidant status, hematological parameters and reduced the lipid peroxidation. The present study revealed that supplementation of vitamin-C in a balanced quantity can be a potent remedy for the protection of chlorpyrifos toxicity in fishes.