Swathi Putta

Synthesis of new secretory phospholipase A2-inhibitory indole containing isoxazole derivatives as anti-inflammatory and anticancer agents

Secretory phospholipase A2 (sPLA2) is an important enzyme that plays a key role in various inflammatory diseases including cancer and its inhibitors have been developed as preventive or therapeutic agents. In the present study, a series of new indole containing isoxazole derivatives (10a-10o) is synthesized and evaluated for their sPLA2 inhibitory activities. All compounds (10a-10o) showed significant sPLA2 inhibition activities both in vitro and in vivo studies which is substantiated in in silico studies. Among all the tested compounds, 10o showed potent sPLA2 inhibition activity, that is comparable or more to ursolic acid (positive control). Further studies demonstrated that 10o showed in vitro antiproliferative activity when tested against MCF-7 breast and DU145 prostate cancer cells. Furthermore, compounds 10a-10o obeyed lipinskys rule of 5 and suggesting druggable properties. The in vitro, in vivo and in silico results are encouraging and warrant pre-clinical studies to develop sPLA2-inhibitory compound 10o as novel therapeutic agent for various inflammatory disorders and several malignancies.

Biological and phytopharmacological descriptions of Litchi chinensis

Plants remain a vital source of drugs and at present, much emphasis is given to nutraceuticals. Herbal medicines have been the basis of treatment and cure for various diseases and physiological conditions in the traditional methods practiced such as ayurveda and homeopathy. Litchi chinensis belongs to the Sapindaceae family and is well-known in the Indian traditional system for its traditional uses. The parts of the plant used are leaves, flowers, fruits, seed, pulp, and pericarp. All parts of the plant are rich sources of phytochemicals––epicatechin; procyanidin A2 and procyanidin B2; leucocyanidin; cyanidin glycoside, malvidin glycoside, and saponins; butylated hydroxytoluene; isolariciresinol; kaempferol; rutin; and stigmasterol. In the present review, we explore the lychees description, traditional medicinal uses, and phytoconstituents, and investigate the pharmacological activities in various parts of the lychee to show its importance in ethanopharmacology. This is so that this review can serve as a ready-to-use material for further research on the plant.

Delayed progression of diabetic cataractogenesis and retinopathy by Litchi chinensis in STZ-induced diabetic rats

Abstract Context: The study was carried out to evaluate the effect of the aqueous fruit pericarp extract of Litchi chinensis (APLC) on parameters which leads to diabetic cataractogenesis and retinopathy in the streptozotocin-induced diabetic rats. Objective: The objective of the study is to evaluate the APLC for in vivo antioxidant activity and its role in inhibiting the polyol pathway and formation of advanced glycation end products (AGEs). Materials and methods: The diabetic animals were treated with L. chinensis for a period of 12 weeks. At the end of 12 weeks, the animals were killed and the biochemical pathways involved in the pathogenesis of cataract such as oxidative stress by protein content, superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and polyolpathway by aldose reductase (AR) in lens homogenates, alterations in protein carbonyl content (PCO) and AGEs in both serum and lens the APLC-treated diabetic rats were compared against diabetic control rats. Cataract progression due to hyperglycemia was monitored by slit lamp bio microscope and classified into four stages. Fundoscope test and retinal histopathology were done for assessing retinopathy. Results: Statistically significant reduction in glucose, and elevation of protein content, SOD, CAT, and GSH levels and decreased levels of AR and PCO in lens homogenate and significant reduction in AGEs serum and lens homogenate were observed. Slit lamp examination, fundoscope, and histopathology showed improvement in retinal changes in APLC-treated rats compared to diabetic control animals. Conclusion: The treatment with APLC found to delay the progression of diabetic cataractogenesis and retinopathy, which might be due to its antioxidant activity, because of the presence of active phytochemicals in APLC.

Therapeutic Potentials of Triterpenes in Diabetes and its Associated Complications.

Diabetes is a major chronic metabolic disorder globally and around of 285 million people are affected by the disease and the number is expected to double in the next two decades. The major focus of anti-diabetic therapies is to enhance insulin production, sensitivity and/or reduce the blood glucose level. Although several synthetic drugs have been developed as antidiabetic agents but their utility has been hampered due to their side effects and poor efficacy. In this scenario, research on natural products has been gained importance due their safety profile in toxicity studies. Terpenoids belong to an important class of natural products and several terpenoids have been reported as antidiabetic agents. Some of them are under various stages of pre-clinical and clinical evaluation to develop them as antidiabetic agents. These agents can inhibit enzymes responsible for the development of insulin resistance, normalization of plasma glucose and insulin levels and glucose metabolism. Triterpenes can act as promising agents in the treatment of diabetic retinopathy, neuropathy and nephropathy or in impaired wound healing by inhibiting several pathways involved in the diabetes and associated complications. However, efforts in understanding the biological actions and clinical studies involving the applications of triterpenes in treating diabetes are very limited. Hence, special attention is imperative to explore the therapeutic potential of these compounds and provide new information to the scientific community. This review aims to provide the recent advances in triterpenes chemistry, its derivatives, biological interventions and its therapeutic applications with special emphasis on diabetes and its associated disorders.

Diabetes Mellitus and Male Aging: Pharmacotherapeutics and Clinical Implications

Andropause or male menopause is defined as androgen decline and onset of hypogonadism in the aging male. Testosterone deficiency in adult male is associated with diabetes mellitus, coronary artery disease, and heart failure. Type 2 diabetic male patients aged above 30 years showed low testosterone levels which is common in diabetic men and had symptoms of hypogonadism. Male sexual dysfunction among diabetic patients can include disorders of libido, ejaculatory problems, and erectile dysfunctions are common among people with diabetes, particularly in older men who had diabetes for years. Older diabetics tend to have both impaired insulin release as well as insulin resistance. There is growing evidence indicating the pathophysiological connections among the mechanisms of oxidative damage by disruption of the oxidative balance, increased levels of enzymatic glycation products in testicular region and glucose transporters, obesity and proinflammatory cytokines in male infertile patients with diabetes. Epidemiological studies suggest that many clinical findings in diabetics are linked to low testosterone levels. This article reviews pathophysiological mechanisms, observational studies, and clinical implications of testosterone therapy in type 2 diabetes mellitus.

Preventive and Therapeutic potentials of Anthocyanins in diabetes and associated complications

Diet is an essential factor affecting the development of and risk for diabetes mellitus. In search of preventative and therapeutic strategies, the potential role of certain foods and their bioactive compounds to prevent the pathogenesis associated with metabolic diseases is to be considered. Human consumption of anthocyanins is among the highest of all flavonoids. Epidemiological studies have suggested that the consumption of anthocyanins lowers the risk of diabetes and diabetic complications. Anthocyanins are important natural bioactive pigments responsible for red to blue colour of fruits, leaves, seeds, stems and flowers, which are present in a variety of plant species particularly in berries and cherries. A large number of bioactive anthocyanins, such as cyanidin, malvidin, delphinidin, pelargonidin, peonidin, petunidin and their metabolites have shown multiple biological activities with apparent effects on glucose absorption, glucose uptake, insulin secretion and sensitivity, on the enzymes involved in glucose metabolism, gene expressions, inflammatory mediators, glucose transporters in progression of diabetes and associated complications, such as diabetic retinopathy, nephropathy, neuropathy and diabetic vascular diseases. The versatility of the anthocyanins provides a promising approach for diabetes management than synthetic drugs. Here we summarize the effect of several anthocyanins on many in vitro, in vivo and clinical studies and also reveal the mechanisms which could prevent or reverse the underlying mechanisms of diabetic pathologies including promotion of antioxidant, antihyperlipidemic, anti-inflammatory and anti-apoptotic activities.

Type 2 Diabetes Study, Introduction and Perspective

CLINICAL TRIAL STUDY Type 2 Diabetes Study, Introduction and Perspective Da-Yong Lu, Jin-Yu Che, Nagendra Sastry Yarla, Hong Zhu, Ting-Ren Lu, Bin Xu and Swathi Putta Shanghai University, Shanghai 200444, P. R. China Divisions of Biochemistry & Chemistry, City University of New York School of Medicine, 160 Convent Avenue, New York, NY 10031, USA College of Pharmaceutical Science, Zhejiang University, Hangzhou, P. R. China Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P. R. China College of Pharmaceutical Science, Andhra University, Visakhapatnam, AP, India

A Critical Appraisal of Different Food Safety and Quality Management Tools to Accomplish Food Safety

Abstract Food safety has become an emerging issue these days, because of the consumer concern as well as the regulatory concerns toward quality and safety of food. Physical, chemical, and biological contaminants action are the tri- factorial causes of food spoilage. To minimize or manage the food safety risk, there is a need to design and implement food safety and quality standards and quality assurance systems in food industries in order to produce safe food. Food safety requires very close concern at all stages in the food chain from farm to folk, which involves the harvesting stage to the consumption stage. Expansion of food supply chain takes place from the regional level to the international level, and therefore there must be a mutual understanding needed between government bodies, manufacturers, and customers. This chapter gives a overview picture of different food safety certification schemes and quality management systems & other popular standards to bring out quality products from a food industry in a safe manner.

Probiotics: Supplements, Food, Pharmaceutical Industry

Abstract Advances in microbiology and molecular biology, along with the adoption of organisms not previously used as probiotics, have contributed to a growing concern about the potential safety of these microorganisms. There was an increased demand day by day for the production and improvement in the safety and quality of probiotics. Probiotics with Lactobacillus, Bifidobacterium, Streptococcus and Enterococcus are widely used as food and drugs. Different varieties of probiotic formulations are available as capsules, liquids, and powders. The strain selection and differentiation was based on the genetic complement with consumers and depends on interactions with co-administered agents or drugs. The first commercially sold dairy based probiotic was Yakult, a fermented milk with added Lactobacillus. Many more probiotic foods have come on the market, including kefir, yogurt, kombucha, kimchi, sauerkraut, other fermented foods and beverages, soft cheeses, probiotic filled drinks, sour dough breads, and milk with probiotics. Physicians have recommended probiotics as supplements to improve the efficacy of the conventional medications in such conditions as alcoholic liver diseases, urinary, respiratory and digestive tract infections, diabetes and cancer. They reduce flatulence and bloating, protect DNA, protect proteins and lipids from oxidative damage, and the maintain individual intestinal microbiota. Research is being done on the combined formulation of selected drugs with probiotics using nanotechnology to improve the patience compliance. Scientifically established health claims are a high priority to companies who seek to promote the health benefits of their particular probiotics.

Inhibition of In Vitro Fructose-Induced Protein Glycation by Litchi chinensis

Non enzymatic glycation is a chain reaction between reducing sugars and the free amino groups of proteins, involved in severity of diabetes and diabetic complications. Litchi chinensis used as consumed fruit and as a drug to treat certain diseases. In this study the antioxidative effects of L.chinensis and also its effect against protein oxidation and advanced glycation end products. The antioxidant potential of aqueous fruit pericarp extract of L.chinensis (APLC) was evaluated in vitro using a model of fructose-mediated protein glycation. The antioxidant activity of APLC conducted for superoxide, hydroxyl, hydrogen peroxide, nitric oxide radical scavenging activities and also demonstrated antioxidant activity with Fe+2 chelating activity, ferric reducing antioxidant power (FRAP) and Trolox equivalent antioxidant capacity (TEAC) were applied. Fructose (100mM) increased fluorescence intensity of glycated bovine serum albumin (BSA) in terms of total AGEs during 21 days of exposure. Moreover, fructose caused more protein carbonyl (PCO) formation in native BSA. The APLC prevents oxidative protein damages including effect on PCO formation which are believed to form under the glycoxidation process. The APLC at different concentrations (25-250μg/ml) has significantly decreased the formation of AGEs in term of the fluorescence intensity of glycated BSA.