Indian folklore medicine in managing men's health and wellness.

India is a home for a large variety of plants with remarkable medicinal and pharmacological value. Traditional medicine in the form of Ayurveda, Siddha and Unani has used many of these plants since ancient days for treating and curing various ailments of the body. When it comes to issues related to reproductive health, people still hesitate to discuss and/or accept it openly and hence look for alternate and natural remedies. The various tribal populations distributed across different parts of the country still use these plant extracts in various formulations for maintenance of good health. The medical utilities of several of these plants have been documented; however, there are many more, whose potential is yet to be explored. This review discusses the role of various plants grown in the Indian subcontinent that have been widely used in maintaining various aspects of reproductive health in men such as infertility, aphrodisiac, contraception, libido, sexually transmitted infections and reproductive tract cancers as well as in treating chronic disorders.

Oxidatively modified phosphatidylserines on the surface of apoptotic cells are essential phagocytic 'eat-me' signals: cleavage and inhibition of phagocytosis by Lp-PLA2.

Diversified anionic phospholipids, phosphatidylserines (PS), externalized to the surface of apoptotic cells are universal phagocytic signals. However, the role of major PS metabolites, such as peroxidized species of PS (PSox) and lyso-PS, in the clearance of apoptotic cells has not been rigorously evaluated. Here, we demonstrate that H2O2 was equally effective in inducing apoptosis and externalization of PS in naive HL60 cells and in cells enriched with oxidizable polyunsaturated species of PS (supplemented with linoleic acid (LA)). Despite this, the uptake of LA-supplemented cells by RAW264.7 and THP-1 macrophages was more than an order of magnitude more effective than that of naive cells. A similar stimulation of phagocytosis was observed with LA-enriched HL60 cells and Jurkat cells triggered to apoptosis with staurosporine. This was due to the presence of PSox on the surface of apoptotic LA-supplemented cells (but not of naive cells). This enhanced phagocytosis was dependent on activation of the intrinsic apoptotic pathway, as no stimulation of phagocytosis occurred in LA-enriched cells challenged with Fas antibody. Incubation of apoptotic cells with lipoprotein-associated phospholipase A2 (Lp-PLA2), a secreted enzyme with high specificity towards PSox, hydrolyzed peroxidized PS species in LA-supplemented cells resulting in the suppression of phagocytosis to the levels observed for naive cells. This suppression of phagocytosis by Lp-PLA2 was blocked by a selective inhibitor of Lp-PLA2, SB-435495. Screening of possible receptor candidates revealed the ability of several PS receptors and bridging proteins to recognize both PS and PSox, albeit with diverse selectivity. We conclude that PSox is an effective phagocytic 'eat-me' signal that participates in the engulfment of cells undergoing intrinsic apoptosis.

Di 2-ethyl hexyl phthalate affects differentiation and matrix mineralization of rat calvarial osteoblasts--in vitro.

Di-2-ethyl hexyl phthalate (DEHP), an industrial plasticizer and a ubiquitous environmental contaminant, is an established endocrine disruptor (ED). Increasing evidences indicate that some EDs interfere with osteoblast differentiation and function. In the present study, we investigated the effects of DEHP on the expression of cell cycle proteins, differentiation markers, Runx2 and its co-activator TAZ in osteoblasts derived from neonatal rat calvaria. A significant decrease in protein levels of cyclin D1 and CDK-2 was found at high dosage of DEHP (100 µM) after 24h treatment. DEHP treatment caused a significant decrease in ALP mRNA. While DEHP treatment significantly decreased the TAZ at mRNA and protein levels, it decreased only the Runx2protein levels. Histochemical localization of ALP, collagen and mineralized nodules studied from cells treated with DEHP (10 and 100 µM) for 21 days revealed a drastic decrease in collagen, ALP and mineralization. In conclusion, DEHP affected differentiation of neonatal rat calvarial osteoblasts and mineralization of matrix secreted by these cells.

Insulin mimetic impact of Catechin isolated from Cassia fistula on the glucose oxidation and molecular mechanisms of glucose uptake on Streptozotocin-induced diabetic Wistar rats.

Diabetes mellitus is the most common and serious metabolic disorder among people all over the world. Many plants have successfully been used to overcome this problem. Cassia fistula, an ethnomedicnal plant, is widely used in Indian medicine to treat diabetes. Methanol extract of stem of plant, reduced the blood glucose levels in Streptozotocin-induced diabetic rats. Bioassay guided fractionation was followed to isolate Catechin from methanol extract. Catechin was administered to Streptozotocin (60mg/kg b.w.)-induced diabetic male Wistar rats at different doses (5, 10, 20mg/kg b.w.) for 6 weeks to assess its effect on fasting plasma glucose. The plasma glucose was significantly (p<0.05) reduced when compared to the control. Oral administration of Catechin (20mg/kg b.w.) markedly increased tissue glycogen, and (14)C-glucose oxidation without any change in plasma insulin and C-peptide. Catechin restored the altered Glucokinase, glucose-6 Phosphatase, Glycogen Synthase and Glycogen Phosphorylase levels to near normal. GLUT4 mRNA and protein expression were enhanced after Catechin treatment. The results of this experimental study indicated that Catechin possesses hypo-glycemic, Glucose oxidizing and insulin mimetic activities and hence it could be used as a drug for treating diabetes.

Studies on hypoglycaemic effects of polyherbal preparation in streptozotocin-induced diabetic male albino rats.

Many traditional treatments have been recommended in the alternative system of medicine for diabetes mellitus. However, the mode of action of most of the herbals used has not been defined. It has been reported that sex hormones are important regulators of insulin-mediated events in skeletal muscles. In view of this, a novel herbal preparation containing antidiabetic and aphrodisiac plants was used in the present study. Adult male albino rats were divided into following groups after induction of diabetes. Rats were given an intraperitoneal (i.p.) injection of streptozotocin (STZ), at a dose of 65 mg/kg body weight after overnight fasting, to induce diabetic state with blood glucose levels >250 mg/dL. Group 1-Control rats treated with single i.p. injection of vehicle, Group 2-Rats treated with polyherbal preparation (PHP; 500 mg/kg body weight by oral intubation, morning and evening for 30 days), Group 3-STZ-diabetic rats treated orally with equal volumes of vehicle (water) alone and Group 4-STZ-diabetic rats treated with PHP after 10 days of diabetic induction. STZ-diabetes decreased the body weight, serum insulin level and glucose oxidation in liver and skeletal muscles but increased the fasting blood glucose level. After polyherbal treatment, body weight and glucose oxidation were completely restored to control level while serum insulin level was restored partially and the glucose tolerance was significantly improved. There was a significant decrease in total haemoglobin (Hb) level of diabetic rats when compared to control but polyherbal treatment significantly improved the same. However, the other parameters studied (red blood cell [RBC], white blood corpuscle [WBC], packed cell volume [PCV], mean corpuscular volume [MCV] and mean corpuscular haemoglobin [MCH]) were unaltered. In conclusion, the anti-diabetic properties of PHP appear to be mediated through pancreatic beta-cell regeneration, resulting in maintenance of optimal blood glucose and its oxidation in liver and skeletal muscles.

Intestinal mucosal alterations in rats with carbon tetrachloride-induced cirrhosis: changes in glycosylation and luminal bacteria.

Spontaneous bacterial peritonitis is a major cause of mortality after liver cirrhosis. Altered permeability of the mucosa and deficiencies in host immune defenses through bacterial translocation from the intestine due to intestinal bacterial overgrowth have been implicated in the development of this complication. Molecular mechanisms underlying the process are not well known. In order to understand mechanisms involved in translocation of bacteria, this study explored the role of oxidative stress in mediating changes in intestinal mucosal glycosylation and luminal bacterial content during cirrhosis. CCl4-induced cirrhosis in rats led to prolonged oxidative stress in the intestine, accompanied by increased sugar content of both intestinal brush border and surfactant layers. This was accompanied by changes in bacterial flora in the gut, which showed increased hydrophobicity and adherence to the mucosa. Inhibition of xanthine oxidase using sodium tungstate or antioxidant supplementation using vitamin E reversed the oxidative stress, changes in brush border membrane sugar content, and bacterial adherence. In conclusion, oxidative stress in the intestine during cirrhosis alters mucosal glycosylation, accompanied by an increased hydrophobicity of luminal bacteria, enabling increased bacterial adherence onto epithelial cells. This might facilitate translocation across the mucosa, resulting in complications such as spontaneous bacterial peritonitis.

Antioxidant effect of ascorbic acid on PCB (Aroclor 1254) induced oxidative stress in hypothalamus of albino rats.

BACKGROUND: PCBs are one of the environmental toxicants and neurotoxic compounds which induce the production of free radicals leading to oxidative stress. Vitamin C is well known as an outstanding antioxidant. We determined the protective role of ascorbate on hypothalamic antioxidant system of Aroclor 1254 exposed rats. METHODS: The rats were injected Aroclor 1254 at a dose of 2 mg/kg bw/day intraperitoneally for 30 days. One group of rats received vitamin C (100 mg/kg bw/day) orally simultaneously with Aroclor 1254 for 30 days. Twenty-four hours after last treatment, the animals were killed and hypothalamic region was separated from brain tissue. Enzymatic and non-enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and vitamin C were estimated. Hydrogen peroxide (H(2)O(2)), lipid peroxidation (LPO) and acetylcholine esterase (AchE) activity were determined. Serum gonadotropins such as luteinizing hormone (LH) and follicle stimulating hormone (FSH) were also assayed. RESULTS: Activities of SOD, CAT, GPx, GR, AchE and the concentration of vitamin C were decreased while an increase in H(2)O(2) and LPO were observed in hypothalamus of PCB treated animals. LH and FSH concentrations were also decreased in serum of PCB exposed animals. Vitamin C administration retrieved all the parameters significantly except serum hormonal profiles. CONCLUSION: PCB induces oxidative stress in hypothalamus by decreasing the activities of antioxidant enzymes, which can be protected by vitamin C treatment.

Surgical manipulation of the intestine and distant organ damage-protection by oral glutamine supplementation.

BACKGROUND: The intestine is increasingly recognized as a primary effector of distant organ damage, such as the lung, after any abdominal surgery. Earlier studies have shown that surgical manipulation of the intestine induces generation of reactive oxygen species in the intestine, resulting in mucosal and lung damage. Because glutamine is preferentially used by the small intestine as an energy source, this study examined the effect of glutamine and glutamic acid on intestinal and lung damage after surgical manipulation. METHODS: Controls and rats were pretreated for 7 days with 2% glutamine or glutamic acid, or the isonitrogenous amino acids glycine or alanine in the diet and subjected to surgical manipulation of the intestine. The intestine and lung were assessed for damage, and protection offered by various amino acids was studied. RESULTS: Surgical manipulation resulted in oxidative stress in the intestine as evidenced by increased xanthine oxidase activity and decreased antioxidant status. Enterocyte mitochondria were also functionally impaired with altered calcium flux, decreased respiratory control ratio, and increased swelling. Gut manipulation also resulted in neutrophil infiltration and oxidative stress in the lung as assessed by an increase in myeloperoxidase activity, lipid peroxidation, and antioxidant status. Glutamine or glutamic acid supplementation for 7 days before surgical manipulation showed a protective effect against the intestinal and lung damage. CONCLUSIONS: This study suggests that preoperative enteral glutamine or glutamic acid supplementation attenuates intestinal and lung damage in rats during surgical manipulation and that this effect might offer protection from postsurgical complications.

Heat preconditioning prevents oxidative stress-induced damage in the intestine and lung following surgical manipulation.

BACKGROUND: The intestine is increasingly recognized as a primary effector of distant organ damage, such as lung, following abdominal surgery. Surgical manipulation of the intestine generates oxygen free radicals resulting in mucosal damage. Heat preconditioning has been proposed to prevent various stress-induced alterations in cells and tissues, including oxidative stress. This study examined the effect of heat preconditioning on oxidative stress-induced damage to the intestine and lung, following surgical manipulation. METHODS: Control rats and rats pretreated with heat were subjected to surgical manipulation by opening the abdominal wall and handling the intestine as done during laparotomy. Intestine and lung were assessed for damage by histology and markers of oxidative stress. RESULTS: Surgical manipulation resulted in ultrastructural changes in the intestine. Biochemical alterations in the enterocytes were evident, with increased xanthine oxidase activity resulting in production of superoxide anion and with a decrease in antioxidant status. Gut manipulation also resulted in neutrophil infiltration and oxidative stress in the lung as assessed by histology, myeloperoxidase activity, lipid peroxidation and antioxidant status. Heat conditioning before surgical manipulation had a protective effect against this intestinal and lung damage. CONCLUSION: This study suggests that mild whole-body hyperthermia before surgery might offer protection from postoperative complications.

Heat preconditioning prevents enterocyte mitochondrial damage induced by surgical manipulation.

BACKGROUND: The small intestine is susceptible to free radical-induced damage and our earlier work has shown that surgical manipulation of the intestine results in generation of oxygen free radicals, leading to mucosal damage. Heat preconditioning has been shown to offer protection against various stresses including oxidative stress and this study looked at the effect of heat preconditioning on surgical manipulation-induced intestinal mitochondrial alterations. METHODS: Control and rats pretreated with heat were subjected to surgical manipulation by opening the abdominal wall and handling the intestine as done during laparotomy. Mitochondria were prepared from isolated enterocytes and structural and functional alterations were assessed. RESULTS: Surgical manipulation of the intestine resulted in mitochondrial alterations as seen by ultrastructural changes and altered lipid composition. Mitochondria were functionally impaired as evidenced by altered calcium flux, decreased respiratory control ratio, and increased tetrazolium dye reduction and swelling. Along with this, biochemical alterations such as increased lipid and protein oxidation were seen following surgical manipulation. Mild heat preconditioning of the animal prevented these damaging effects. CONCLUSIONS: These studies suggest that stress in the small intestine due to surgery can affect enterocyte mitochondrial structure and function and these effects can be prevented by mild whole body hyperthermia prior to surgery.

Heat preconditioning attenuates oxygen free radical-mediated alterations in the intestinal brush border membrane induced by surgical manipulation.

BACKGROUND: The intestine is highly susceptible to free radical-induced damage and our earlier work has shown that surgical manipulation of the intestine results in generation of oxygen free radicals and mucosal damage along with alterations in the brush border membrane (BBM). Heat preconditioning is known to offer protection against various stresses including oxidative stress and this study looked at the effect of heat preconditioning on the intestinal BBM alterations following surgical manipulation. METHODS: Control and rats heat preconditioned were subjected to surgical manipulation by opening the abdominal wall and handling the intestine. BBM were isolated from the intestine and structural and functional alterations to these membranes were assessed. RESULTS: Surgical manipulation resulted in oxidative stress suggested by a decrease in alkaline phosphatase activity and alpha-tocopherol content, accompanied by an increase in lipid peroxidation. A decrease in glucose transport by the isolated BBM vesicles suggested functional impairment. Surgical manipulation resulted in phospholipid degradation with generation of arachidonic acid along with appearance of cPLA(2) in the membrane. These changes were prevented by heat preconditioning of the animal prior to surgical manipulation. CONCLUSION: These results suggest that heat preconditioning offers protection from damage to the intestinal BBM following surgical manipulation and mild whole body hyperthermia might prevent postsurgical complications.

Enhancement of beta-glucosidase and beta-galactosidase of Trigonella foenum-graecum by exposure to the allelochemical mimosine.

Glycohydrolases assume significance in the metabolism of biological systems and have important industrial applications in the areas of pharmaceuticals, food, and medicine. Glycosidases were screened in germinating seeds, and attempts were made to enhance their levels. Screening of glycosidases in the seedlings during a 72 h germination period revealed higher levels of beta-glucosidase and beta-galactosidase in Trigonella foenum-graecum compared to Cicer arietinum and Vigna radiata. Activity of beta-galactosidase was in general higher than that of beta-glucosidase in all the seedlings tested. During growth, exposure of the seedlings to an allelochemical, mimosine, at 0.1 mM resulted in the enhancement of enzyme levels by 50% in the seedlings of T. foenum-graecum, whereas the addition of mimosine to the assay medium in vitro did not affect the enzyme activities. Hydrolytic activity was enhanced by addition of glycerol in the medium up to 0.1 M in the case of beta-glucosidase and with 0.05 M in the case of beta-galactosidase. In general, the hydrolytic rate was higher by about 30% in the seedlings exposed to mimosine compared to that of the control. Concomitant enhancement in the rates of transgalactosidation by 51% and transglucosidation by 23% was also noted, underscoring the relevance of plant glycohydrolases for appropriate applications.

Glutathione modulates lipid composition of human colon derived HT-29 cells.

Glutathione (GSH) is important in maintaining intracellular thiol status. The present study looked at the effect of GSH depletion on lipid composition of colon-derived HT-29 cells. GSH was depleted in HT-29 cells by incubation either with buthionine-S, R-sulfoximine (BSO) or diethylmaleate (DEM). GSH was restored during early periods of cells growth by supplementation of growth medium with either GSH ester or N-acetyl cysteine (NAC). Lipids were analysed following GSH depletion and supplementation. Among the neutral lipids, an increase in free cholesterol and diacylglycerol and decrease in cholesteryl ester and triacylglycerol were seen in GSH-depleted cells as compared to control cells. There were no detectable free fatty acids either in control or GSH-depleted cells. Among the phospholipids, a decrease in phosphatidylcholine and phosphatidylinositol and an increase in phosphatidylethanolamine were observed. These changes were a completely reversed by supplementation of BSO-treated cells with GSH ester and partially reversed by N-acetyl cysteine. These results suggest that the GSH status of the cell plays an important role in the lipid composition of the cells.

Effect of enterotoxin on glutathione status in the intestinal mucosa.

The effect of luminal exposure of enterotoxins on the intestinal mucosal glutathione (GSH) was studied in rat. Cholera toxin induced fluid secretion and decreased mucosal GSH by 35% without altering oxidized glutathione (GSSG) level. Toxin induced fluid secretion was tested after mucosal GSH depletion by compounds such as diethyl maleate (DEM) and buthionine sulfoximine (BSO) and thiol supplementation with N-Acetyl cysteine (NAC). Fluid secretion was not altered by prior thiol depletion or supplementation. Exposure of intestinal lumen to bacterial endotoxin resulted in 25% decrease in mucosal GSH with two fold increase in GSSG. Luminal exposure of Shiga toxin did not alter the mucosal thiol. The level of other low molecular weight thiols, cysteine and cystine was not altered by luminal exposure of any of these toxins. These results show that although cholera toxin decreased the mucosal GSH level, prior modulation of thiol status of the mucosa may not have any effect on toxin-induced fluid secretion.

Specific activities of seminal vesicular phosphomonoesterases and Mg2+-,Ca2+- and Na+/K(+)-adenosine triphosphatases in hypo- and hyperthyroid albino rats.

Hypothyroidism (surgical thyroidectomy) inhibited the activities of acid phosphatase and Mg(2+)-ATPase in seminal vesicular tissue and fluid and that of Ca(2+)- and Na+/K(+)-ATPases in fluid alone, and T4 supplementation restored normalcy in all, except acid phosphatase. Hyperthyroidism (T4 25 micrograms/100g body weight/day for 60 days, im) enhanced the activities of alkaline phosphatase and ATPases in seminal vesicular tissue and fluid, and decreased acid phosphatase activity in tissue alone. Withdrawal of T4 treatment from hyperthyroid rats (after 30 days) augmented the activity of ATPases in tissue and impaired the same in fluid, while phosphomonoesterases remained at hyperthyroid level. The results suggest specific responses of various seminal vesicular phosphatases to altered thyroid hormone status. Modification in the specific threshold of androgen/estrogen action on different phosphatases in seminal vesicles appears to be the plausible mechanism underlying these changes in hypo- and hyperthyroid conditions.

Therapeutic potential and clinical efficacy of acid-resistant fungal lipase in the treatment of pancreatic steatorrhoea due to cystic fibrosis.

We investigated the therapeutic potential of an acid-resistant fungal lipase prepared from Aspergillus niger. We first demonstrated in vitro that it had a wide pH optimum of 2.5-5.5 and was resistant to pepsin and trypsin. We gave the enzyme or matching placebo in random order by mouth with a fatty meal to 10 adult patients with pancreatic steatorrhoea due to cystic fibrosis (CF) and sampled gastric contents for the following 2 h. Mean acid-resistant lipase activity was 330 nmol/ml/min free fatty acid released on placebo, compared with 896 nmol/ml/min on fungal lipase (p = 0.006 for area under the curve). We compared this lipase's clinical efficacy with that of two conventional pancreatin microsphere formulations in an open randomised crossover fat-balance study in 10 similar patients. Each preparation was given for 2 weeks, and a fat-balance study, using a faecal recovery marker, was performed on the final 3 days; a period without treatment was also included. The fungal lipase had no effect on faecal wet weight or on the coefficient of fat absorption (59.0% vs. 52.3%; NS) in comparison with placebo. The established enteric-coated microsphere preparation (Creon) produced a significant reduction in faecal wet weight and improvement in coefficient of fat absorption (81.4% vs. 52.3%; p less than 0.01) in comparison with placebo. The newer microsphere preparation (Pancrex M) was also effective, but perhaps less so than Creon; there were no significant differences between the two preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Formation of methylglyoxal by bacteria isolated from human faeces.

Bacteria present in the human gut may produce methylglyoxal--a cytotoxic substance in mammals. This was investigated by studying the activity of methylglyoxal synthase, which produces methylglyoxal from dihydroxyacetone phosphate, and methylglyoxal concentration in growth medium of various bacteria isolated from human faeces. Facultative and strictly anaerobic bacteria isolated from faeces were able to produce methylglyoxal in both defined and complex media. Proteus spp. produced large amounts of methylglyoxal and had the greatest methylglyoxal synthase activity. Supplementing defined medium for facultative anaerobes with glucose 1% w/v did not significantly alter enzyme activity or methylglyoxal production. Inclusion of short chain fatty acids or bile acids in the medium reduced methylglyoxal synthase activity and methylglyoxal production by Proteus spp. None of the organisms examined had amine oxidase activity which could have contributed to methylglyoxal production from aminoacetone.

Faecal free fatty acids in tropical sprue and their possible role in the production of diarrhoea by inhibition of ATPases.

Faecal excretion of fatty acids is increased in patients with tropical sprue because of unabsorbed dietary fatty acids. The excretion of fatty acids correlates well with faecal wet weight. In vitro unsaturated fatty acids inhibited Na K-ATPase and Mg-ATPase isolated from basolateral membranes of enterocytes and colonocytes. These findings are a possible explanation for the observed abnormalities in water and electrolyte absorption by the colon in patients with tropical sprue and steatorrhoea.