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Prevention of anticancer drugs-induced cardiotoxicity remains an imperative area of oncology research as it continues to be a major challenge in cancer chemotherapy. This study was undertaken to investigate the protective effect of methanol extract of Morchella esculenta (ME) against cyclophosphamide (CP)-induced cardiotoxicity. Myocardial damage was assessed by biochemical and histopathological methods. Proinflammatory cytokines gene expression was determined by RT-PCR analysis. To assess the mitochondrial dysfunction, TCA cycle and electron transport chain complexes enzymes activities were determined. Chemical finger print of ME was accomplished by HPTLC. CP (200 mg/kg) treated animals showed elevation in cardiac injury markers which was attenuated by ME (p < 0.05). CP-induced decline of antioxidant status and expression of nuclear factor erythroid 2-related factor 2 were restored by ME. CP-induced expression of NF-ĸB, IL1-ß, IL-6, TNF-α, COX-2 and iNOS (p < 0.05) was attenuated by ME (500 mg/kg). Bioactive compounds namely, 5-eicosapentaenoicacid (C20H30O2), 8-hydroxyoctadecadienoic acid (C18H32O3), 4,4-dipo-zetacarotene (C30H44), CynarosideA (C21H32O10) present in the extract might be responsible for cardioprotection. The findings reveal the protective effect of ME against CP-induced cardiomyopathy.

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Morel mushrooms, Morchella species are highly nutritious and excellently edible wild mushrooms abundantly growing in Kashmir Himalayas. The free radical scavenging, anti-inflammatory, and arthritis edema-inhibiting properties of bioactive extract of Morchella elata (EAE) were evaluated. EAE inhibited 53.2% formalin-induced paw edema at a dose of 500 mg/kg b.wt and 75.0% croton oil-induced skin inflammation at a dose of 50 mg topical application. EAE exhibited 51.8% COX inhibiting activity at a concentration of 100 µg/ml when assayed using LPS-stimulated RAW 264.7 cells exposed to the extract. NF-kB inhibiting activity of EAE was assayed using Lentix-293T P65 Ds Red stable cell line. High-throughput fluorescent imaging and flow cytometry showed profound ability of EAE to inhibit NF-kB activity. HPTLC analysis revealed that EAE is composed of several chemical components. The mushroom is a source of therapeutically useful functional food that can provide relief in arthritis.

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Alpha-lipoic acid (ALA) is a naturally occurring dithiol micronutrient which acts as a cofactor for mitochondrial enzyme activity. Due to its potential antioxidant activity, it is considered as "universal antioxidant". Previous studies reported the pharmacological benefits of ALA such as glycaemic control, improved insulin sensitivity and alleviation of diabetic complications such as neuropathy and cardiovascular diseases. Dry eye disease and retinopathy are prevalent in diabetic patients. Experimental studies demonstrated the beneficial effects of ALA in dry eye and diabetic retinopathy. ALA can prevent the dry eye by down regulating the expression of matrix metalloproteinase-9 in the corneal epithelial cells and activating the antioxidant status of the ocular surface. Furthermore, its direct antioxidant effect can also prevent oxidative stress-induced corneal surface erosion and lachrymal gland damage. ALA prevents diabetic retinopathy through inhibition of O-linked ß-N-acetylglucosamine transferase and nuclear factor-kappa B activity and alleviation of oxidative stress. It can activate the nuclear factor erythroid-2-related factor 2 and AMP-activated protein kinase in retinal ganglion cells. Clinical trials conducted in pre-retinopathic diabetic patients showed ALA with genistein and vitamins could protect the retinal cells and decline the inflammatory effect in diabetic patients. However, studies are scant to explore its beneficial effects in dry eye disease and diabetic retinopathy. Therefore, this review article discusses an update on the role of ALA in dry eye disease and diabetic retinopathy, two ocular diseases prevalent in diabetic patients.

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Magnesium (Mg2+) is one of the major elements required to maintain normal metabolism and ionic balances in ocular tissues. The physiological role of Mg2+ is mediated through maintaining the Na+-K+-ATPase on membrane, favoring energy-generating reactions, replication of DNA and protein synthesis. Despite the wide availability of this element, hypomagnesemia has been associated with many human ailments. Recent studies highlighted the association of hypomagnesemia and, thereby, supplementation of Mg2+ in the management of eye diseases. Glaucoma, senile cataract and diabetic retinopathy were associated with low level of extracellular Mg2+. The neurovascular protective effects of Mg2+ mediated through activation of endothelial nitric oxide synthase and inhibition of endothelin-1 eventually result in vasodilatation of retinal vessels. Mg2+ can maintain the lens sodium pump activity and antioxidant status and block the calcium channels and release of glutamate in nerve endings. Furthermore, it can prevent the apoptosis of retinal ganglion cells. All these effects contribute to its being a pharmacological agent against ocular diseases. However, clinical trials are scant. This article discusses the role of Mg2+ as a possible therapeutic agent in the management of glaucoma, cataract and diabetic retinopathy.

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Incidence of coronary heart disease (CHD) increases worldwide with varying etiological factors. In addition to the control of risk factors, dietary modification has been recommended to reduce the prevalence. Omega-3 (ω-3) fatty acids (FAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), of fish oil are beneficial for the prevention of CHD. The effect can be ascribed to anti-inflammatory, vasodilating, antiarrhythmic, antihypertensive activities and lowering of triacyl glycerol level. The American Heart Association advises two fish meals per week in subjects without CHD or supplementation of 1 g of EPA plus DHA per day in subjects with CHD. Despite the beneficial effects of EPA/DHA reported in some of the clinical trials, results of many others were inconsistent that can be ascribed to short duration of studies, low doses of ω-3 FAs, variations in the EPA:DHA ratio, selection of patients with different risk factors or interaction of ω-3 FAs with drugs used in the therapy. Therefore, well designed clinical trials in various populations are warranted. This article discusses the current situation and future prospective of ω-3 FAs in CHD.

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Hypoxia-inducible factors (HIFs) are transcription factors that are expressed in the hypoxic tumor microenvironment. They are involved in the cellular adaptations by improving the metabolism of glucose and enhance the expression of vascular endothelial growth factor, platelet-derived growth factor and angiopoietin, thereby they play a pivotal role in the angiogenesis. Hypoxia can increase the expression of nuclear factor-kappa B which promotes the pro-inflammatory status. Abnormally high angiogenesis, inflammation, antiapoptosis and anaerobic glycolysis can augment the progression and metastasis of tumor. Hence, HIFs remain one of the promising antiangiogenic agents as well as a direct target for interfering with the energetic of cancer cells in order to regulate the tumor growth. Previous studies found agents like topotecan, acriflavine and benzophenone-1B etc. to block the HIF-α mediated angiogenesis. The effect is mediated through interfering any one of the processes in the activation of HIF such as nuclear translocation of HIF-1α; dimerization of HIF-1α with ß in the nucleus; HIF-1α/HIF-2α mediated induction of VEGF or translation of HIF-1α mRNA. Despite the experimental studies on the inhibitory molecules of HIFs, none of them are available for the clinical use. This review article discusses the recent update on the HIF-targeted therapy in cancer.

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OBJECTIVE: Chemopreventive agents which exhibit activities such as anti-inflammation, inhibition of carcinogen induced mutagenesis and scavenging of free radical might play a decisive role in the inhibition of chemical carcinogenesis either at the initiation or promotion stage. Many synthesized palladium (Pd) complexes tested experimentally for antitumor activity are found effective. Poly-MVA is a liquid blend preparation containing B complex vitamins, ruthenium with Pd complexed with alpha lipoic acid as the major ingredients. The antitumor effect of Poly-MVA was evaluated against 7,12-dimethylbenz[a] anthracene-initiated croton oil-promoted papilloma formation on mice skin. Skin tumor was initiated with a single application of 390 nmol of DMBA in 20 µl acetone. The effect of Poly-MVA against croton oil- induced inflammation and lipid peroxidation on the mice skin was also evaluated. Topical application of Poly-MVA (100 µl, twice weekly for 18 weeks) 30 minutes prior to each croton oil application, significantly decreased the tumor incidence (11%) and the average number of tumor per animals. Application of Poly-MVA (100 µl) before croton oil significantly (p &#60; 0.05) protected the mouse skin from inflammation (36%) and lipid peroxidation (14%) when compared to the croton oil alone treated group. Experimental results indicate that Poly-MVA attenuate the tumor promoting effects of croton oil and the effect may probably be due to its anti-inflammatory and antioxidant activity.

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Advanced glycation end products (AGE) such as N-ε-carboxy-ethyl-lysine (CEL), N-ε-carboxy-methyl-lysine (CML), imidazolone, methyl-glyoxal-lysine dimer (MOLD), glyoxal-lysine dimer (GOLD), pyrraline and pentosidine have been imparted in the development and worsening of complications of diabetes. They are also involved in atherosclerosis, normal aging process, arthritis, cancer and progression of age-related neurodegenerative diseases like Alzheimer`s disease. Endogenously, they are formed by nonenzymatic glycation by aldoses/ketoses to form intermediate precursor that were slowly converted into AGE. A positive correlation was observed with the level of AGEs formation and progression of the diseases. Exogenously, they formed in foods when they were cooked at very high temperature. AGEs can interact with the cell surface receptors of AGE (RAGE) to release cytokines, free radicals as well as directly modify the extracellular matrix and action of hormones. Hence, the mechanism of AGE association with pathogenesis of diseases can be ascribed mainly to the generated cytokines and free radicals. Second type of receptors such as AGE receptor-1, 2 and 3 were more specific and involved in their detoxification and clearance. Therapeutic agents were used to inhibit AGEs formation, traps the reactive carbonyl intermediate precursors, interfering with Amadori`s products, cross-link breaker and low molecular weight inhibitors of RAGE had been described as well. Despite the several therapeutic agents described so far, none of them have proven to be recommended for clinical use. Furthermore, no methods or standard units were accepted universally to measure AGEs are existing. This review discusses AGEs formation, association with diseases and therapeutic agents to alleviate them.

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Phellinus rimosus is a parasitic host specific polypore mushroom with profound antioxidant, antihepatotoxic, anti-inflammatory, antitumor, and antimutagenic activities. This study investigated the hypoglycemic and hypolipidemic activities of the wood-inhabiting polypore mushroom Ph. Rimosus in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by single intraperitoneal injection of STZ (45 mg/kg) to Wistar rats. The effects of 30 days treatment with Ph. Rimosus (50 and 250 mg/ kg) and glibenclamide (0.65 mg/kg) on blood glucose level, serum insulin, serum lipid profile, liver glycogen, liver function enzymes, and non-enzymic and enzymic antioxidants activities in pancreas, liver, and kidney were evaluated in STZ-induced diabetic rats. Oral administration of Ph. Rimosus extract exhibited a significant reduction in blood glucose, triacylglycerol, total cholesterol, LDL-cholesterol, and liver function enzymes, and increased serum insulin, liver glycogen, and HDL-cholesterol levels in STZ-induced diabetic rats. Furthermore, Ph. Rimosus treatment increased antioxidant status in pancreas, liver, and kidney tissues with concomitant decreases in levels of thiobarbituric acid- reactive substances. Results of this study indicated that Ph. Rimosus possessed significant hypoglycemic and hypolipidemic activities and this effect may be related to its insulinogenic and antioxidant effect.

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Association between amyloid-ß (Aß) toxicity, mitochondrial dysfunction, oxidative stress and neuronal damage has been demonstrated in the pathophysiology of Alzheimer's disease (AD). In the early stages of the disease, the defect in energy metabolism was found to be severe. This may probably due to the Aß and ROS-induced declined activity of complexes in electron transport chain (ETC) as well as damages to mitochondrial DNA. Though clinically inconclusive, supplementation with antioxidants is reported to be beneficial especially in the early stages of the disease. A mild to moderate improvement in dementia is possible with therapy using antioxidants viz coenzyme Q10 (ubiquinone), α -lipoic acid, selenium, omega-3 fatty acids and vitamin E, emphasize their possible role as an adjuvant with the existing conventional treatment. Since mitochondrial dysfunction has been observed, a new therapeutic strategy called as 'Mitochondrial Medicine' which is aimed to maintain the energy production as well as to ameliorate the enhanced apoptosis of nerve cells, has been developed. Mitochondrial CoQ10, Szeto-Schiller peptide-31 and superoxide dismutase/ catalase mimetic, EUK-207 were the mitochondrial targeted agents demonstrated in experimental studies. This article discusses the mitochondrial impairment and the possible mitochondria targeted therapeutic intervention in AD.

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Alcohol abuse and alcoholism remain one of the major health issues worldwide, especially in developing countries. The protective effect of Phellinus rimosus against acute alcohol-induced lipid peroxidation in the liver, kidney, and brain as well as its effect against antioxidant enzyme activity such as superoxide (SOD) and catalase (CAT) in the liver was evaluated in mice. Ethyl acetate extract of Ph. Rimosus (50 mg/kg body wt, p.o.) 1 h before each administration of alcohol (3 mL/kg, p.o.; total 2 doses at 24-h intervals) protected against lipid peroxidation in all organs and attenuated the decline of SOD and CAT activity in the liver. The fold increase in lipid peroxidation, including conjugated diene and thiobarbituric acid reactive substance (TBARS) levels, was highest in the liver. There were 2.6- and 1.5- fold increases in TBARS levels in the liver of the alcohol alone- and alcohol+Ph. Rimosus-treated groups, compared with that of the normal group. Activity of SOD and CAT in the liver of alcohol- and alcohol+Ph. Rimosus- treated animals was 9.05±1.38, 18.76±1.71, and 11.26±1.02, 31.58±3.35 IU/mg protein, respectively. Extract at 1 mg/mL inhibited 50.6% activity of aniline hydroxylase (CYP2E1) in liver homogenate. From these results, we concluded that the extract significantly protected against the lipid peroxidation. Protection in the liver may be due to the inhibitory effect on CYP2E1 as well as the direct radical scavenging effect of Ph. Rimosus, which warrants further research.

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Diabetes is usually associated with increased production of reactive oxygen species (ROS), impaired antioxidant defense systems, or both, which result in oxidative damage and lead to ROS-mediated diabetic pathogenesis. This investigation was undertaken to evaluate the role of extract from the wood-inhabiting polypore medicinal mushroom Phellinus rimosus in an alloxan-induced diabetic model and the oral glucose tolerance test in rats. Oral administration of extract at doses of 50 and 250 mg/kg body weight/day for 10 days to rats with alloxan-induced diabetes was found to possess significant dose-dependent hypoglycemic activity. In the oral glucose tolerance test, hypoglycemic effect of P. rimosus (250 mg/kg) was significant (P < 0.01) and maximum at 90 minutes after the glucose challenge when compared with that of control group. The effect of extract on antioxidant status in the pancreas, liver, and kidney was estimated. The diabetic control rats exhibited elevated levels of lipid peroxidation and lower activities of copper/zinc superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) content in pancreatic, hepatic, and renal tissues compared with normal tissues. The activities of SOD, CAT, GPx, and GSH were found to be increased in diabetic rats treated with the extract. The increased level of lipid peroxidation in diabetic rats also was found to revert to near-normal status in groups treated with the extract. The findings thus suggest the therapeutic efficiency of Ph. Rimosus against declined antioxidant status as well as hyperglycemia associated with diabetes.

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