Flavonoids: A Reservoir of Drugs from Nature.

Flavonoids are associated with many plants and dietary foods; their chemical study has always attracted the interest of chemists working in the area of natural products and synthetic chemistry. Research in phytochemistry has produced many useful drugs. The analogs of flavonoids exhibit anticancer, anti-tuberculosis, anti-diabetic, antiviral, antibacterial, antioxidant, anti-inflammatory, antiproliferative, anti-spermatogenic, and antipsychotic activities. This review article highlights flavonoids' significance and medicinal application and displays a comparative overview of the biological activities of flavonoids and flavonoid derivatives. It covers almost all necessary reports for future directions in drug discovery.

Microcystin-leucine arginine (MC-LR) induces bone loss and impairs bone micro-architecture by modulating host immunity in mice: Implications for bone health.

Osteoporosis or enhanced bone loss is one of the most commonly occurring bone conditions in the world, responsible for higher incidence of fractures leading to increased morbidity and mortality in adults. Bone loss is affected by various environmental factors including diet, age, drugs, toxins etc. Microcystins are toxins produced by cyanobacteria with microcystin-LR being the most abundantly found around the world effecting both human and animal health. The present study demonstrates that MC-LR treatment induces bone loss and impairs both trabecular and cortical bone microarchitecture along with decreasing the mineral density and heterogeneity of bones in mice. This effect of MC-LR was found due to its immunomodulatory effects on the host immune system, wherein MC-LR skews both T cell (CD4+ and CD8+ T cells) and B cell populations in various lymphoid tissues. MC-LR further was found to significantly enhance the levels of osteoclastogenic cytokines (IL-6, IL-17 and TNF-α) along with simultaneously decreasing the levels of anti-osteoclastogenic cytokines (IL-10 and IFN-γ). Taken together, our study for the first time establishes a direct link between MC-LR intake and enhanced bone loss thereby giving a strong impetus to the naïve field of "osteo-toxicology", to delineate the effects of various toxins (including cyanotoxins) on bone health.

Amelioratory effect of coenzyme Q10 on potential human carcinogen Microcystin-LR induced toxicity in mice.

Microcystins are a group of cyclic heptapeptide toxins produced by cyanobacteria. More than 100 microcystin analogues have been detected, among which microcystin-LR is the most abundant and toxic variant. Present study was designed to reveal whether potential human carcinogen microcystin-LR could imbalance the glycolytic-oxidative-nitrosative status of heart, kidney and spleen of mice and also to explore the amelioratory effect of coenzyme Q10 on microcystin-LR induced toxicity. Microcystin-LR was administered at a dose of 10 µg/kg bw/day, ip for 14 days in male mice. In microcystin-LR treated mice as compared to control, significant increase in the level of lipid peroxidation, hydrogen peroxide, lactate dehydrogenase, nitric oxide with a concomitant decrease in the level of glutathione was observed, suggesting microcystin-LR induced toxicity via induction of oxidative-nitrosative-glycolytic pathway. Although several studies have evaluated numerous antioxidants but still there is no effective chemoprotectant against microcystin-LR induced toxicity. When microcystin-LR treated mice were co-administered coenzyme Q10 (10 mg/kg bw/day, im) for 14 days, it was observed that coenzyme Q10 ameliorates microcystin-LR induced toxicity via modulation of glycolytic-oxidative-nitrosative stress pathway. Thus, the results suggest that coenzyme Q10 has a potential to be developed as preventive agent against microcystin-LR induced toxicity.

Microcystin-LR Induced Immunotoxicity in Mammals.

Microcystins are toxic molecules produced by cyanobacterial blooms due to water eutrophication. Exposure to microcystins is a global health problem because of its association with various other pathological effects and people all over the world are exposed to microcystins on a regular basis. Evidence shows that microcystin-LR (MC-LR) may adversely affect the immune system, but its specific effects on immune functions are lacking. In the present review, immunotoxicological effects associated with MC-LR in animals, humans, and in vitro models have been reported. Overall, the data shows that chronic exposure to MC-LR has the potential to impair vital immune responses which could lead to increased risk of various diseases including cancers. Studies in animal and in vitro models have provided some pivotal understanding into the potential mechanisms of MC-LR related immunotoxicity suggesting that further investigation, particularly in humans, is required to better understand the relationship between development of disease and the MC-LR exposure.

Effect of certain entomopathogenic fungi on oxidative stress and mortality of Periplaneta americana.

The present paper reports the effects of Metarhizium anisopliae, Isaria fumosoroseus and Hirsutella thompsonaii on Periplaneta americana. I. fumosoroseus and H. thompsonaii were cultured at 28±1°C on potato carrot agar and M. anisopliae was cultured at 28±1°C on potato dextrose agar for 14days. Conidial suspensions of fungi were given to cockroaches through different routes. M. anisopliae shows high virulence against adult cockroaches and mortality ranges from 38.65% to 78.36% after 48h. I. fumosoroseus and H. thompsonii show less virulence compared to M. anisopliae. We also investigated the effect of these three fungi on the activity of lactate dehydrogenase, lipid peroxidation and catalase in different tissues of the insect to gain an understanding of the different target site. The result suggested that the activity of lactate dehydrogenase, catalase and level of malondialdehyde varies in different organs and through different routes of exposure. Based on mortality percentages, all tested fungi had high potentials for biocontrol agents against P. americana. Our study reveals for the first time that I. fumosoroseus and H. thompsonaii fungal infections initiate oxidative stress in the midgut, fat body, whole body and hemolymph of cockroach thereby suggesting them to be the target organs for oxidative damage.

An overview of the toxic effect of potential human carcinogen Microcystin-LR on testis.

The worldwide occurrence of cyanobacterial blooms due to water eutrophication evokes extreme concerns. These blooms produce cyanotoxins which are hazardous to living organisms. So far among these toxins, Microcystin-LR (MC-LR) is the most toxic and the most frequently encountered toxin produced by the cyanobacteria in the contaminated aquatic environment. Microcystin-LR is a potential carcinogen for animals and humans, and the International Agency for Research on Cancer has classified Microcystin-LR as a possible human carcinogen. After liver, testis has been considered as one of the most important target organs of Microcystin-LR toxicity. Microcystin-LR crosses the blood-testis barrier and interferes with DNA damage repair pathway and also increases expression of the proto-oncogenes, genes involved in the response to DNA damage, cell cycle arrest, and apoptosis in testis. Toxicity of MC-LR disrupts the motility and morphology of sperm and also affects the hormone levels of male reproductive system. MC-LR treated mice exhibit oxidative stress in testis through the alteration of antioxidant enzyme activity and also affect the histopathology of male reproductive system. In the present review, an attempt has been made to comprehensively address the impact of MC-LR toxicity on testis.