Medicinal mushrooms occurring in South India namely Ganoderma lucidum, Phellinus rimosus, Pleurotus florida and Pleurotus pulmonaris possessed profound antioxidant and antitumor activities. This indicated that these mushrooms would be valuable sources of antioxidant and antitumor compounds. Investigations also revealed that they had significant antimutagenic and anticarcinogenic activities. Thus, Indian medicinal mushrooms are potential sources of antioxidant and anticancer compounds. However, intensive and extensive investigations are needed to exploit their valuable therapeutic use.
Traditional Medicines derived from medicinal plants are used by about 60% of the world's population. This review focuses on Indian Herbal drugs and plants used in the treatment of diabetes, especially in India. Diabetes is an important human ailment afflicting many from various walks of life in different countries. In India it is proving to be a major health problem, especially in the urban areas. Though there are various approaches to reduce the ill effects of diabetes and its secondary complications, herbal formulations are preferred due to lesser side effects and low cost. A list of medicinal plants with proven antidiabetic and related beneficial effects and of herbal drugs used in treatment of diabetes is compiled. These include, Allium sativum, Eugenia jambolana, Momordica charantia Ocimum sanctum, Phyllanthus amarus, Pterocarpus marsupium, Tinospora cordifolia, Trigonella foenum graecum and Withania somnifera. One of the etiologic factors implicated in the development of diabetes and its complications is the damage induced by free radicals and hence an antidiabetic compound with antioxidant properties would be more beneficial. Therefore information on antioxidant effects of these medicinal plants is also included.
Understanding of the efficacy and mechanism for the reaction of the biologically important radicals with natural and/or synthetic antioxidants is the first step towards the development of future therapeutic agents. The kinetic parameters e.g., formation and decay rate constants predict the efficacy of an antioxidant and its fate after reaction. These parameters also dictate the ease with which competing reactions would occur in a bio-environment. The spectroscopic parameters provide the clue to the site of free radical attack to these antioxidants. Here, in this article an attempt has been made to show the use of physico-chemical methods in the evaluation of antioxidant activity of some important medicinal plants commonly used in India and the subcontinent. The systems chosen here for discussions are herbal extracts as such, curcumin from turmeric, methoxy phenols from Indian spices, dehydrogingerdione from ginger and bakuchiol from Psoralea corylifolia. All the examples shown in this article illustrate the potential of the pulse radiolysis coupled with kinetic spectroscopy and other physicochemical techniques for the study of antioxidants either in the form of mixture as in herbal extract or as an isolated compound.
To elucidate the roles of enteric bacteria and immunological interactions among liver, spleen and intestine in the pathogenesis of liver injury during obstructive jaundice, we studied the effects of antibiotics and splenectomy on bile-duct-ligated C57BL mice. When animals were subjected to bile-duct-ligation (BDL), plasma levels of bilirubin, alanine aminotransferase and aspartate aminotransferase increased markedly. However, the increases in plasma transaminases were significantly lower in splenectomized or antibiotics-treated groups than in the control BDL group. Histological examination revealed that liver injury was also low in the two groups. BDL markedly increased plasma level of interferon-γ (IFN-γ) and the expression of inducible nitric oxide synthase (iNOS) in liver and spleen. These changes were suppressed either by splenectomy or administration of antibiotics. Kinetic analysis revealed that BDL-induced liver injury and the increase of interleukin-10 (IL-10) and INF-γ were lower in iNOS−/− than in wild type animals. BDL markedly increased the expression of IgA in colonic mucosa. These observations suggest that enteric bacteria, nitric oxide and cytokines including IFN-γ and IL-10 derived from spleen and intestines form a critical network that determines the extent of liver injury during obstructive jaundice.
The effects of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase), on oxidative stress resistance and the protective effects of coenzyme Q (CoQ) were investigated. When simvastatin was administered orally to mice, the levels of oxidized and reduced CoQ9 and CoQ10 in serum, liver, and heart, decreased significantly when compared to those of control. The levels of thiobarbituric acid reactive substances induced by Fe2+-ascorbate in liver and heart mitochondria also increased significantly with simvastatin. Furthermore, cultured cardiac myocytes treated with simvastatin exhibited less resistance to oxidative stress, decreased time to the cessation of spontaneous beating in response to H2O2 addition, and decreased responsiveness to electrical field stimulation. These results suggested that oral administration of simvastatin suppresses the biosynthesis of CoQ, which shares the same biosynthesis pathway as cholesterol up to farnesyl pyrophosphate, thus compromising the physiological function of reduced CoQ, which possesses antioxidant activity. However, these undesirable effects induced by simvastatin were alleviated by coadministering CoQ10 with simvastatin to mice. Simvastatin also reduced the activity of NADPH-CoQ reductase, a biological enzyme that converts oxidized CoQ to the corresponding reduced CoQ, while CoQ10 administration improved it. These findings may also support the efficacy of coadministering CoQ10 with statins.
The development of multiple gastric cancer is a major problem after the endoscopic resection of the first early gastric cancer. To find out markers to identify high risk patients, we analyzed the microsatellite instability (MSI) status and hypermethylation of tumor-related genes in multiple gastric cancers. Sixty-four adenocarcinomas resected by endoscopy, including 32 early solitary gastric cancers (SGCs) from 32 patients and 32 multiple gastric cancers (MGCs) from 14 patients, were employed. We analyzed MSI and the methylation status of promoter regions of the hMLH1, MGMT, p16 and E-cadherin using methylation-specific Polymerase Chain Reaction. Expression levels of hMLH1 were examined by immunohistochemistry. MSI (+) was detected in 5 of the 14 (35.7%) patients with MGCs, and in only 3 of the 32 patients (9.3%) with SGCs. Significant differences were observed between the 2 groups (p<0.001). Hypermethylation of hMLH1 was more frequently detected in MGCs than in SGCs (p<0.01), whereas significant difference was not observed in the frequency of MGMT, p16 or E-cadherin promoter methylation between the 2 groups. In conclusion, our results indicate that inactivation of hMLH1 through promoter hypermethylation may be involved in the development of multiple gastric cancers following the MSI pathway.
The mechanisms that cause chemoresistance of gastric cancer have yet to be elucidated. Taxanes and promising agents that were recently approved for treatment of advanced or recurrent gastric cancer. Mutations of beta-tubulin, which is a target of taxianes, have been shown to confer chemoresistance against these agents. The aim of the present study is to investigate the presence of mutations of the beta-tubulin in gastric cancer tissues. Sixty-six patients with advanced stage III or IV gastric cancer patients enrolled in this study. Paired samples of gastric cancer tissue and normal mucosa were obtained by endoscopy. The guanosine 5'-triphosphate (GTP)-binding site in exon 4 of the beta-tubulin gene was examined by polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) analysis, followed by sequencing of the products with abnormally shifted bands. SSCP analysis showed abnormal bands upstream of the GTP-binding site in 7 of the 66 patients, but sequence analysis found no nucleotide substitutions in these patients. Three variant bands were also detected down stream of the the GTP-binding site, but the sequences of the 3 products corresponded to those of two independent pseudogenes. Thus, none of the tumor samples showed mutation of the beta-tubulin exon 4 GTP-binding site. In conclusion, these findings suggest that mutations of the beta-tubulin gene are rare and are unlikely to be an important cause of taxane resistance to taxians.
Small intestinal resection rats are used widely as a malabsorption model, but the immunological changes are unclear. We examined the changes in systemic and mucosal immune status after a small intestinal resection in rats with a controlled nutritional status. Rats had 60% of their small intestine removed. At 5 days after the surgery, spleen cells and intraepithelial lymphocytes (IEL) were isolated. The phenotypes of spleen cells and IEL, the production patterns of Th1 and Th2 cytokines, and the proinflammatory cytokine levels in the plasma were measured. CD4+ T cells in the blood and spleen were significantly decreased in the Resection group (p<0.05). In contrast, IEL subpopulations were not different between the two groups. Interferon-γ production from the spleen cells was significantly decreased in the Resection group (p<0.05). Interleukin (IL)-4 production was not different between the two groups. Plasma IL-6 concentrations were significantly elevated in the Resection group 6 h after surgery (p<0.05). In conclusions, small intestinal resection in rats suppressed systemic immunity, and this model is useful as a surgical stress model.
The amount of phosphorus contained in food as food additives is currently increasing and a high intake of phosphorus can cause various diseases. To determine the effects of a prolonged high phosphorus diet, here we investigated the phosphorus and calcium balance and expression of type IIa sodium-dependent phosphate transporter (Npt IIa) in mature rats. Wistar male rats (8-weeks old) were divided into five groups and fed diets containing 0.6% calcium plus 0.3, 0.6, 0.9, 1.2 or 1.5% phosphorus for 4 weeks. Urinary and fecal phosphorus excretions were significantly increased by the high phosphorus diets (from 0.6 to 1.5%), dependent on the amount of dietary phosphorus. The net absorption of intestinal phosphorus was also significantly increased by high phosphorus diets. As a result, a negative phosphorus balance was observed in rats given the 1.2% or 1.5% phosphorus diets. Serum parathyroid hormone and 1,25-dihydroxyvitamin D3 concentrations were increased by high phosphorus diets. In addition, high phosphorus diets decreased the expression of Npt IIa mRNA and protein in the renal brush border membrane. Taken together, these results suggest that diets containing 1.2 or 1.5% phosphorus plus 0.6% calcium have potentially adverse effects on phosphorus homeostasis in mature rat.
Medicinal plants constitute an important source of potential therapeutic agents for diabetes. In the present study, we investigated the effects of Moringa oleifera (MO) Lam, Moringacea, on glucose tolerance in Wistar rats and Goto-Kakizaki (GK) rats, modeled type 2 diabetes. Major polyphenols in MO powder were quercetin glucosides, rutin, kaempferol glycosides and chlorogenic acids by HPLC analysis. As the results of glucose tolerance test, MO significantly decreased the blood glucose at 20, 30, 45and 60 min for GK rats and at 10, 30 and 45 min for Wistar rats (p<0.05) compared to the both controls after glucose administration. The area under the curve of changes in the blood glucose was significantly higher in the GK control group than in the GK plus MO group (p<0.05) in the periods 30-60 min and 60-120 min. Furthermore, MO significantly decreased stomach emptying in GK rats (p<0.05). The results indicated that MO has an ameliorating effect for glucose intolerance, and the effect might be mediated by quercetin-3-glucoside and fiber contents in MO leaf powder. The action of MO was greater in GK rats than in Wistar rats.
Abdominal obesity is a principal risk factor in the development of metabolic syndrome. Previously, we showed that a palatinose-based liquid formula, Inslow/MHN-01, suppressed postprandial plasma glucose level and reduced visceral fat accumulation better than the standard formula (SF). To elucidate the mechanism of Inslow-mediated anti-obesity effect, expression levels of genes involved in the glucose and lipid metabolism were compared in Inslow- and SF-fed rats. Both fasting plasma insulin level and average islet sizes were reduced in the Inslow group. We also found less abdominal fat accumulation and reduced hepatic triacylglycerol content in the Inslow group. Expression of the β-oxidation enzymes and uncoupling potein-2 (UCP-2) mRNAs in the liver of the Inslow group were higher than the SF group, which was due to a concomitant higher expression of the peroxisome proliferator-activated receptor (PPAR)-α mRNA in the former. Furthermore, expression of the UCP-2 and adiponectin mRNAs in the epididymal fat were higher in the Inslow group than the SF group, and were stimulated by a concomitant increase of the PPAR-γ gene expression in the former. These results strongly suggested that the anti-obesity effect of Inslow was due to an increase in the hepatic PPAR-α and adipocyte PPAR-γ gene expressions.