Effect of brahma rasayana on antioxidant system after radiation.

Oral administration of brahma rasayana (BR; 50 mg/animal for 10 and 30 days) significantly increased the liver antioxidant enzymes such as superoxide dismutase (SOD), catalase(CAT) and tissue and serum levels of reduced glutathione (GSH). Whole body irradiation suppressed the levels of SOD, CAT and GSH. Reduced activity of SOD, CAT and GSH was significantly elevated by treatment with BR after radiation treatment. Similarly radiation exposure induced increase in serum and liver lipid peroxides was significantly reduced by further treatment with BR. The results indicate that BR could ameliorate the oxidative damage produced in the body by radiation and may be useful as an adjuvant during radiation therapy.

Cancare-a herbal formulation inhibits chemically induced tumours in experimental animals.

Cancer chemopreventive potential of Cancare, a multi-herbal formulation on chemically induced tumours was studied by N-nitrosodiethylamine (NDEA) induced hepatocarcinogenesis in rats and 20-methylcholanthrene (20-MC) induced sarcoma development in mice. Oral administration of Cancare was found to inhibit the liver tumour development induced by N-nitrosodiethylamine. Animals administered with NDEA had visible liver tumours by the end of 30th weeks and the liver weight was raised to 6.1 +/- 1.4 g/ 100 g body wt. None of the animals treated with Cancare (150 mg/ kg) developed any visible liver tumours by this period and the liver weight was 3.0 +/- 0.6 g/ 100 g body wt. Gamma-Glutamyl transpeptidase, a marker of hepatocellularcarcinoma, which was raised to 83.7 +/- 8. 9 U/l in serum of NDEA treated group was reduced to 35.2 +/- 6.1 U/l by simultaneous administration of Cancare. Elevated levels of serum alkaline phosphatase, glutamate pyruvate transaminase, bilirubin, liver glutathione S-transferase, glutathione and gamma-Glutamyl transpeptidase in the NDEA administered group was significantly reduced by Cancare administration. Cancare administration inhibited the sarcoma development and increased the life span of mice administered with 20-MC dose dependently. All animals in the control group developed sarcomas by 150th day and dead by 174th day after 20-MC administration. Cancare administration (30 mg and 150 mg/kg) inhibited the sarcoma development (46.7 and 60%) as well as increased the life span (53.3 and 66.7%) as estimated on 240th day after 20-MC administration. The results are indicative of the chemopreventive potential of Cancare against chemically induced neoplasmas.

Antioxidant activity of brahma rasayana.

Free oxygen radical scavenging activity of brahma rasayana (BR) was studied by in vitro and in vivo models. Addition of aqueous extract of BR was found to scavenge the lipid peroxides already present in rat liver homogenate (IC50 700 micrograms/ml) and inhibit the lipid peroxide generated by Fe(2+)-ascorbate (IC50 2600 micrograms/ml) and Fe(3+)-ADP-ascorbate system (IC50 1200 micrograms/ml). BR was found to scavenge the hydroxyl radical generated by Fenton reaction (IC50 7400 micrograms/ml) and superoxide generated by photoreduction of riboflavin (IC50 180 micrograms/ml). BR was also found to inhibit the nitric oxide radical generated in vitro from sodium nitroprusside (IC50 5.5 micrograms/ml). Oral administration of BR (50 mg/dose/animal) was found to inhibit the PMA induced superoxide generation in mice peritoneal macrophages. Oral administration of BR; 10 and 50 mg/dose/animal was also found to inhibit the nitrite production in peritoneal macrophages and percentage inhibition was 25.2% and 37.8% respectively. These results indicate significant antioxidant activity of BR in vitro and in vivo.

Effect of herbal preparation, brahma rasayana, in amelioration of radiation induced damage.

Oral administration of brahma rasayana (BR; 10 and 50 mg/dose/animal) for 15 days increased significantly total leukocyte count and percentage of polymorphonuclear cells in irradiated mice. Bone marrow cellularity and alpha-esterase positive cells also increased significantly in radiation-treated animals after BR administration. Number of nodular colonies on the surface of spleen on day seven increased significantly in lethally irradiated recipients receiving bone marrow cells from animals treated with BR. Oral administration of BR also enhanced in serum level of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and granulocyte macrophage-colony stimulating factor(GM-CSF) in normal and irradiated mice. These results indicated that proliferation of stem cells induced by BR in irradiated mice may be related to its stimulation of cytokine production.

Antioxidant and anticarcinogenic activity of Lycovin--an indigenous herbal preparation.

Aqueous extract of Lycovin has been found to be a potent inhibitor of lipid peroxide formation, (IC50 = 500 micrograms/ml) and scavenger of hydroxyl radical (IC50 = 44 micrograms/ml) and superoxide radical (IC50 = 30 micrograms/ml) in vitro. Lycovin syrup 1.5 ml and 7.5 ml/kg body wt administered orally, reduced the development of sarcoma induced by 20 MC by 35% and 70% respectively. Lycovin syrup was also found to inhibit the hepatocarcinogenesis induced by NDEA. The tumour incidence was 100% in the control group, while none of the drug treated animals developed tumour. Liver weight, gamma-glutamyl transpeptidase (GGT), GSH-S-transferase (GST), reduced glutathione, (GSH) and aniline-4-hydroxylase in liver were elevated in NDEA alone treated animals. The serum parameters indicative of liver injury such as bilirubin, lipid peroxides, alkaline phosphatase and glutamate pyruvate transaminase were also elevated by NDEA administration. These elevated parameters were significantly reduced in animals treated with Lycovin syrup along with NDEA in a dose dependent manner. Even though the exact mechanism of action is not known at present, the observed anticarcinogenic activity may be due to the inhibition of P.450 enzyme activity and subsequent inhibition of the production of the ultimate carcinogen as well as scavenging of oxygen free radicals during promotion of the transformed cell.

Effect of "rasayanas", a herbal drug preparation on immune responses and its significance in cancer treatment.

Rasayanas are considered to be immunostimulating preparations used extensively in indigenous medical practice. However there are only very few reports to substantiate this claim, and this paper gives preliminary evidence for the potentiation of immunity by Rasayanas given to mice orally. Administration of Rasayanas were found to enhance the proliferation of spleen cells significantly especially in the presence of mitogen. Similar result was also seen with bone marrow cells; however mitogenic stimulation could not be observed. Esterase activity was found to be enhanced in bone marrow cells indicating increased maturation of cells of lymphoid linkage. Rasayanas also enhanced humoral immune response as seen from the increased number of antibody forming cells and circulating antibody titre. These results indicate the usefulness of Rasayana as immunostimulating agent.

Effect of "rasayanas" a herbal drug preparation on cell-mediated immune responses in tumour bearing mice.

Administration of herbal preparation, Rasayanas has been found to enhance the natural killer cell activity in normal as well asin tumour bearing animals. Brahma Rasayana (BR) was found to have the maximum activity. BRand Aswagandha Rasayana (AR) were found to activate antibody-dependent cellular cytotoxicity significantly. AR was also found to activate macrophages. All the Rasayanas were found to stimulate antibody dependent complement mediated tumour cell lysis. The results of these studies indicate usefullness of Rasayanas for immunostimulation in normal and in disease state.

Immunopotentiating activity of septilin.

Oral administration of septilin (100mg/animal/dose; five doses) was found to enhance natural killer cell mediated cytotoxicity and antibody-dependent cellular cytotoxicity in normal mice as well as tumour-bearing mice. Septilin treatment also activated the peritoneal macrophages which produced cytotoxicity to L929 cells. Septilin increased proliferation of bone-marrow cells and there was an increase in the number of alpha-naphthyl acetate esterase staining cells in the bone-marrow. In addition to the activation of cellular immunity, septilin was found to increase the number of antibody producing cells in the spleen and activation of antibody-dependent complement-mediated cell lysis. These studies justifies the use of this herbal preparation in improving immunocompetence in disease states.

Inhibition of liver fibrosis by ellagic acid.

Chronic administration of carbon tetrachloride in liquid paraffin (1.7) ip; 0.15 ml, (20 doses) has been found to produce severe hepatotoxicity, as seen from the elevated levels of serum and liver glutamate-pyruvate transaminase, alkaline phosphatase and lipid peroxides. The chronic administration of carbon tetrachloride was also found to produce liver fibrosis as seen from pathological analysis as well as elevated liver-hydroxy proline. Oral administration of ellagic acid was found to significantly reduce the elevated levels of enzymes, lipid peroxide and liver hydroxy proline in these animals and rectified liver pathology. These results indicate that ellagic acid administration orally can circumvent the carbon tetrachloride toxicity and subsequent fibrosis.

Protective effect of curcumin, ellagic acid and bixin on radiation induced toxicity.

Whole body irradiation of rats (10 Gy as five fractions) found to produce lung fibrosis within 2 months as seen from increased lung collagen hydroxyproline and histopathology. Oral administration of antioxidants curcumin, ellagic acid, bixin and alpha-tocopherol at a concentration 200 mumole/kg body weight significantly reduced the lung collagen hydroxyproline in these animals. In serum and liver lipid peroxidation which were found to be increased by irradiation was reduced significantly by antioxidant treatment. The liver superoxide dismutase and glutathione peroxidase activity were also found to be increased and catalase activity decreased in irradiated control. Superoxide dismutase activity reduced significantly by antioxidant treatment while catalase activity was found to be increased with alpha-tocopherol treatment. The increased frequency of micronucleated polychromatic erythrocytes after whole body irradiation of mice was found to be significantly reduced with antioxidants.

Radioprotective effects of Rasayanas.

Oral administration of Rasayanas (indigenous preparations made up of herbal drugs) significantly increased total WBC count, bone marrow cellularity, natural killer cell and antibody dependent cellular cytotoxicity in gamma radiation (4 Gy) exposed mice. Also, Rasayanas reduced radiation induced lipid peroxidation in liver. The possible mechanisms of action of Rasayanas could be increased stem cell proliferation and its effect on free radical induced injury produced by radiation.

Mutagenicity and anti-mutagenicity of selected spices.

Using Salmonella typhimurium strains TA 100 and TA 1535, the mutagenicity and anti-mutagenicity of extracts of several spices were checked. Spices like pepper, pippali, ginger and mustard increased the number of revertants indicating their mutagenic potential. Garlic extract on the other hand was found to inhibit the mutagenicity produced by direct acting mutagens such as N-methyl N'-nitro-N-nitrosoguanidine and sodium azide. Asafoetida and turmetic extract were found to inhibit microsomal activation dependent mutagenicity of 2-acetamidofluorene. Similar results were also obtained using curcumin and eugenol which are phenolics present in turmeric and clove respectively. These results indicated that some of the spices may ameliorate the effect of environmental mutagens especially present in the food.

Inhibition of tumour promotion in mice by eugenol.

Number of tumours (papillomas) produced by the application of 7,12-dimethyl benz (a) anthracene as initiator and croton oil promoter in mice were considerably inhibited (84%) by the prior application of eugenol. Moreover, there was considerable decrease in the number of tumour bearing animals and their onset. Eugenol inhibited superoxide formation and lipid peroxidation and the radical scavenging activity may be responsible for its chemopreventive action.

Inhibition of lipid peroxidation and cholesterol levels in mice by curcumin.

Effect of oral administration of curcumin (diferuloyl methane) on lipid peroxidation in various organs of mice like liver, lung, kidney and brain was studied in control animals as well as those given carbon tetrachloride, paraquat and cyclophosphamide. Oral administration of curcumin significantly lowered the increased peroxidation of lipids in these tissues produced by these chemicals. Administration of curcumin was also found to lower significantly the serum and tissue cholesterol levels in these animals, indicating that the use of curcumin helps in conditions associated with peroxide induced injury such as liver damage and arterial diseases.

Effect of oral curcumin administration on serum peroxides and cholesterol levels in human volunteers.

The effect of curcumin administration in reducing the serum levels of cholesterol and lipid peroxides was studied in ten healthy human volunteers, receiving 500 mg of curcumin per day for 7 days. A significant decrease in the level of serum lipid peroxides (33%), increase in HDL Cholesterol (29%), and a decrease in total serum cholesterol (11.63%) were noted. As curcumin reduced serum lipid peroxides and serum cholesterol, the study of curcumin as a chemopreventive substance against arterial diseases is suggested.

Unique bioactivation of tiazofurin--studies with resistant cells.

Using resistant cells mechanism of action of new oncolytic nucleoside, tiazofurin (2-beta-D-ribofuranosyl thiazole-4 carboxamide, RTC) was studied in tissue cultured cells of Chinese Hamster Ovary cells (CHO-cells). Tiazofurin got converted in CHO-cells to tiazofurin-monophosphate and to NAD-analogue, a potent inhibitor of inosinate dehydrogenase. Resistant cells produced tiazofurin-5'-monophosphate in vitro but had a much reduced capacity to produce NAD-analogue, indicating absence of any effect of tiazofurin on incorporation of [14C]formate into guanine, inhibition of inosinate dehydrogenase as well as GTP levels in resistant cells. Using competition with various possible substrates it is found that the initial tiazofurin metabolism is catalysed by nicotinamide nucleoside kinase and NAD-analog formation is mediated by NAD-pyrophosphorylase. Decreased activity of the latter enzyme found in tiazofurin resistant cells not only inhibited the NAD analog formation from tiazofurin-5'-monophosphate but also the NAD-formation from nictotinamide-5'-monophosphate.

Detection and estimation of 3,4-dehydroproline.

A method has been described for the detection and estimation of 3,4-dehydroproline using initial oxidation with isatin or H2O2 and subsequent reaction with p-dimethylamino benzaldehyde (Ehrlich reagent). The method is sensitive enough to detect as low as 0.6 micrograms of 3,4-dehydroproline/sq. cm on paper chromatogram. 3,4-dehydroproline could also be estimated by the classical H2O2-oxidation procedure employed for hydroxyproline apparently yielding the same chromophore on a molar basis. However, when estimated by the chloramine-T oxidation method, its sensitivity was only 1/100th of that of 4-hydroxyproline. The usefulness of these procedures in the detection and estimation of 3,4-dehydroproline has been described.

Effect of gold thiomalate on cell proliferation and collagen synthesis of synovial cells in culture.

Human synovial cells from cases of rheumatoid and osteoarthritis were cultured and at their 3-5 passages, were treated with gold thiomalate. At early-log phase gold thiomalate arrested the proliferation of cells. However, at confluent state shere was a slight proliferation of synovial cells. This was followed by an increase in prolyl hydroxylase, collagen and protein synthesis, indicating that gold salts directly stimulate the synovial cells.