Antitumour activity of Emblica officinalis

Aqueous extract of Emblica officinalis (E.O) was found to be cytotoxic to L 929 cells in culture in a dose dependent manner. Concentration needed for 50% inhibition was found to be 16.5 microg/ml. E.O and chyavanaprash (a non-toxic herbal preparation containing 50% E.O) extracts were found to reduce ascites and solid tumours in mice induced by DLA cells. Animals treated with 1.25 g/kg b.wt. of E.O extract increased life span of tumour bearing animals (20%) while animals treated with 2.5 g/kg b.wt. of chyavanaprash produced 60.9% increased in the life span. Both E.O and chyavanaprash significantly reduced the solid tumours. Tumour volume of control animals on 30th day was 4.6 ml where as animals treated with 1.25 g/Kg b.wt. of E.O extract and 2.5 g/kg b.wt. of chyavanaprash showed a tumour volume of 1.75 and 0.75 ml, respectively. E.O extract was found to inhibit cell cycle regulating enzymes cdc 25 phosphatase in a dose dependent manner. Concentration needed for 50% inhibition of cdc 25 phosphatase was found to be 5 microg/ml and that needed for inhibition of cdc2 kinase was found to be >100 microg/ml. The results suggest that antitumour activity of E.O extract may partially be due to its interaction with cell cycle regulation.     

Antitumour property and toxicity of Barringtonia racemosa Roxb seed extract in mice

Ethnomedical survey has shown that the seeds of Barringtonia racemosa Roxb are traditionally used in certain remote villages of Kerala (India) to treat cancer like diseases. So the seed extracts were tested for their antitumour activity and toxicity. Intraperitoneal (i.p.) daily administration of 50% methanol extract of this seed to mice challenged with 1 million Dalton's Lymphoma Ascitic (DLA) cells resulted in remarkable dose dependent anti-DLA activity in mice. The optimum dose was found to be 6 mg/kg. This dose protected all the animals challenged with the tumour cells. The efficacy of the drug was found to be better than that of a standard drug, vincristine in this tumour model. However, the oral administration showed only marginal activity compared to i.p. administration. The extract was found to be devoid of conspicuous acute and short-term toxicity to mice, when administered daily, (i.p.) for 14 days up to a dose of 12 mg/kg (which was double the concentration of optimum therapeutic dose). The treated mice showed conspicuous toxic symptoms only at 24 mg/kg. The LD(50) to male mice for a single i.p. dose was found to be 36 mg/kg. The seed extract is an attractive material for further studies leading to drug development.     

Evaluation of antidepressant activity of methanolic and hydroalcoholic extracts of Acorus calamus L. rhizome through tail suspension test and forced swimming test of mice

ObjectiveAcorus calamus (AC) L. (Araceae) is an annual semi-aquatic and aromatic plant found in Europe, North America and Asia. Its rhizomes are often used by Native Americans, Americans, and Chinese as well as by other cultures. Ethnobotanical studies and documents have shown their use in various disease treatments, such as insomnia, mental disorders, diabetes mellitus, epilepsy, inflammation, asthma, neuropathic pain, and diarrhea. In this study, the antidepressant activity of methanolic and hydroalcoholic extracts of the AC rhizome part in mice was investigated.MethodsThree doses of methanolic extract of AC rhizome (MEACR) (25, 50 and 100 mg/kg b.wt), three doses of hydroalcoholic extract of AC rhizome (HAACR) (100, 200 and 400 mg/kg b.wt), and standards (imipramine, 15 mg/kg b.wt and fluoxetine, 20 mg/kg b.wt) was daily oral administration to the mice for consecutive 14 days. The extract effect on the immobility time was monitored by a tail suspension test (TST) and a forced swimming test (FST). Monoamine oxidase (MAO) levels were also analyzed using standard methods.ResultsThe optimum antidepressant activity was viewed at 100 mg/kg b.wt of MEACR extract and 400 mg/kg b.wt of HAACR extract with 23.82% and 20.59% immobility period reduction, respectively. Besides, the extracts weakened the FST-induced elevation of MAO activity significantly and returned to near-normal levels of neurotransmitters in the brain. 100 mg/kg b.wt or above of MEACR extract significantly prevented the MAO-A and MAO-B activities in mice brain at a dose-dependent fashion. But, just 400 mg/kg b.wt of HAACR extract prevented the activity of MAO-A and MAO-B. Fluoxetine and imipramine showed a tendency to prevent the activity of MAO-A and MAO-B.ConclusionThis study suggests that AC rhizome extract mediated antidepressant activity by modulating the central neurochemical and hypothalamic-pituitary-adrenal (HPA) axis in response to FST and TST-induced stress. Therefore, AC rhizome extract can be used as a valuable plant supplement to treat depressive disorders.     

In vitro cytotoxic and antitumor property of Emilia sonchifolia (L.) DC in mice

Methanolic extract of Emilia sonchifolia (Compositae), a folklore medicinal plant, was found to be cytotoxic to Daltons lymphoma (DL), Ehrlich ascites carcinoma (EAC) and mouse lung fibroblast (L-929) cells, but not toxic to normal human lymphocytes, under in vitro conditions. Oral administration of the extract (100 mg/kg, b. wt) to mice reduced the development of both solid and ascites tumors and increased the life span of these tumor bearing mice. Further, the extract inhibited DNA synthesis as judged from a reduction in tritiated thymidine incorporation into DL cells under in vitro conditions.     

Effect of Picrorrhiza kurroa extract on transplanted tumours and chemical carcinogenesis in mice

Anti-tumour and anti-carcinogenic activity of Picrorrhiza kurroa extract were studied in mice. Administration of 20-methylcholanthrene (20 MC) produced 100% induction of sarcoma in control mice, whereas the tumour incidence and tumour related deaths were significantly inhibited by the oral administration of P. kurroa extract 150 and 750 mg/kg body weight, respectively. The extract was also found to reduce the volume of transplanted solid tumours induced by Dalton's lymphoma ascites (DLA) tumour cell lines and increased the life span of ascites tumour bearing mice. P. kurroa extract inhibited yeast topoisomerase I and II enzyme activity when tested on Saccharomyces cerevisiae mutant cell cultures. The extract did not inhibit the enzyme involved in the activation of carcinogen and the cell cycle regulatory enzyme cdc2 kinase.     

Evaluation of chemopreventive action and antimutagenic effect of the standardized Panax ginseng extract, EFLA400, in Swiss albino mice

In the present investigation the chemopreventive action and antimutagenic effects of a standardized Panax Ginseng extract (EFLA400, processed Panax ginseng extract containing a high titre of ginsenoside Rg3 (>3.0% w/w) known as Phoenix ginseng) in Swiss albino mice have been evaluated. The oral administration of EFLA400 at 1, 3 and 10 mg/kg body weight at pre, peri and post-initiational phases, showed significant reductions in the number, size and weight of the papillomas. A significant reduction in tumour incidence (71.41 +/- 6.73%, 72.19 +/- 4.54% and 70.46 +/- 0.38% at 1, 3 and 10 mg/kg body weight, respectively) was observed in animals in the EFLA400 treated group compared with 100% tumour incidence in the control group. The cumulative number of papillomas during an observation period of 16 weeks was significantly reduced in the EFLA400 treated group (24 +/- 0.94, 16 +/- 1.41 and 11 +/- 1.41 at 1, 3 and 10 mg/kg body weight, respectively). However, the average latent period was significantly increased from 10.81 +/- 0.1 weeks in the control group to 12.39 +/- 0.28 weeks in the treated group (10 mg/kg body weight). The average tumour weight was recorded as 128.55 +/- 8.48, 116.00 +/- 8.48 and 57.5 +/- 3.29 mg in 1, 3 and 10 mg/kg body weight EFLA400 treated groups respectively. Chromosomal aberrations and micronuclei induction was also evaluated in bone marrow cells. These genotoxicity end-points were compared with papilloma occurrence at the same dose levels of carcinogen and ginseng. In the EFLA400 treated groups significantly reduced frequencies of chromosomal aberrations and micronuclei induced by DMBA and croton oil were observed. However, the maximum decrease in the frequencies of chromosomal aberrations and micronuclei were recorded in the 10 mg/kg body weight EFLA400 treated group than that of the 1 and 3 mg/kg body weight EFLA400 treated animals. The results from the present study suggest the dose dependent effectiveness of EFLA400 in chemoprevention and antimutagenicity in Swiss albino mice.     

Anti-diabetic activity of green tea polyphenols and their role in reducing oxidative stress in experimental diabetes

An aqueous solution of green tea polyphenols (GTP) was found to inhibit lipid peroxidation (LP), scavenge hydroxyl and superoxide radicals in vitro. Concentration needed for 50% inhibition of superoxide, hydroxyl and LP radicals were 10, 52.5 and 136 micro g/ml, respectively. Administration of GTP (500 mg/kg b.wt.) to normal rats increased glucose tolerance significantly (P<0.005) at 60 min. GTP was also found to reduce serum glucose level in alloxan diabetic rats significantly at a dose level of 100 mg/kg b.wt. Continued daily administration (15 days) of the extract 50, 100 mg/kg b.wt. produced 29 and 44% reduction in the elevated serum glucose level produced by alloxan administration. Elevated hepatic and renal enzymes produced by alloxan were found to be reduced (P<0.001) by GTP. The serum LP levels which was increased by alloxan and was reduced by significantly (P<0.001) by the administration of 100 mg/kg b.wt. of GTP. Decreased liver glycogen, after alloxan administration showed a significant (P<0.001) increase after GTP treatment. GTP treated group showed increased antioxidant potential as seen from improvements in superoxide dismutase and glutathione levels. However catalase, LP and glutathione peroxidase levels were unchanged. These results indicate that alterations in the glucose utilizing system and oxidation status in rats increased by alloxan were partially reversed by the administration of the glutamate pyruvate transaminase.     

Cytotoxic and antitumour activity from Bursera fagaroides ethanol extract in mice with L5178Y lymphoma

Chloroform extracts of Bursera fagaroides (Burseracea) have previously shown antitumour activity against the Walker carcinoma 256 tumour system (WA16). In the present work we have determined the cytotoxic and antitumour activity of the ethanol extract (70%) of the bark of B. fagaroides using the L5178Y lymphoma. The cytotoxic activity is expressed as the ED₅₀ of the L5178Y lymphoma cells in culture, (20 µg/mL) whilst the antitumour activity was shown via a tumour growing inhibition test, measuring survival of BALB/c mice (2 × 10⁴ cells L5178Y i.p.). 24 h after inoculation mice were treated with 50 or 100 mg/kg of extract daily, over 15 days in independent groups of 10, using two administration routes. We observed the tumour evolution with and without treatment. Oral administration resulted in 8% of mice being tumour free after 60 day whilst intraperitoneal administration showed 26% survived at a dose of 100 mg/kg/day for 15 days. A significant increase in the survival of the treated animals (at 50 mg/kg/day over 15 days) was found compared with those treated with placebo or without treatment. Copyright © 1998 John Wiley & Sons, Ltd.     

Effect of Withania somnifera on DMBA induced carcinogenesis

Administration of an extract of Withania somnifera was found to reduce two stage skin carcinogenesis induced by DMBA (dimethyl benzanthracene) and croton oil. Withania somnifera was administered at a concentration of (20 mg/dose/animal i.p.) consecutively on 5 days prior to DMBA administration and continued twice weekly for 10 weeks. After the 180th day of carcinogen administration, all of the animals developed papilloma in the control group whereas only six out of 12 animals developed papilloma in the treated group. A total of 11 papillomas were found in the control group while only six developed them in the Withania somnifera treated group. Enzyme analysis of skin and liver showed significant enhancement in antioxidant enzymes such as GSH, GST, Glutathione peroxides and Catalases in Withania somnifera treated group when compared with the control. The elevated level of lipid peroxide in the control group was significantly inhibited by Withania somnifera administration. These studies indicate that Withania somnifera could reduce the papilloma induced alterations to the antioxidant defense systems.     

Immunomodulatory and antitumor activity of Piper longum Linn. and piperine

Alcoholic extract of the fruits of the plant Piper longum and its component piperine was studied for their immunomodulatory and antitumor activity. Alcoholic extract of the fruits was 100% toxic at a concentration of 500 microg/ml to Dalton's lymphoma ascites (DLA) cells and 250 microg/ml to Ehrlich ascites carcinoma (EAC) cells. Piperine was found to be cytotoxic towards DLA and EAC cells at a concentration of 250 microg/ml. Alcoholic extract and piperine was also found to produce cytotoxicity towards L929 cells in culture at a concentration of 100 and 50 microg/ml, respectively. Administration of alcoholic extract of Piper longum (10 mg/dose/animal) as well as piperine (1.14 mg/dose/animal) could inhibit the solid tumor development in mice induced with DLA cells and increase the life span of mice bearing Ehrlich ascites carcinoma tumor to 37.3 and 58.8%, respectively. Administration of Piper longum extract and piperine increased the total WBC count to 142.8 and 138.9%, respectively, in Balb/c mice. The number of plaque forming cells also enhanced significantly by the administration of the extract (100.3%) and piperine (71.4%) on 5th day after immunization. Bone marrow cellularity and alpha-esterase positive cells were also increased by the administration of Piper longum extract and piperine.     

Treatment of mice with a herbal preparation (mentat) protects against radiation-induced mortality

The effect of various doses (0, 5, 10, 20, 40, 80, 100, 120 and 160 mg/kg b. wt.) of 50% ethanolic extract of mentat (a herbal preparation) was studied on the survival of mice exposed to 10 Gy of gamma-radiation. Treatment of mice with different doses of mentat consecutively for fi ve days before irradiation delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the non-drug treated irradiated controls. Most of the doses of mentat provided protection against the gastrointestinal (GI) death, however, the highest protection against GI death was observed for 80 mg/kg mentat. This was also true for bone marrow deaths, where the highest number of survivors were observed at 30 days post-irradiation in this group (i.e. 80 mg/kg) when compared with the other doses of mentat. The evaluation of acute toxicity showed that mentat was non-toxic up to a dose of 1.5 g/kg b. wt., where no drug-induced mortality was observed. The LD50 dose of mentat was found to be 1.75 g/kg b. wt. Our study demonstrates that mentat can provide good radioprotection at a dose of 80 mg/kg, which is far below its toxic dose.     

Evaluation of antidiabetic, antioxidant and vasoprotective effects of Posidonia oceanica extract

The aim of this study is to evaluate antidiabetic, antioxidant and vasoprotective effects of Posidonia oceanica extract (POE) in alloxan diabetic rats. Posidonia oceanica (L) Delile (Posidoniaceae), is a widely allocated phanerogam in Mediterranean and Aegean Sea. Up to date, no published data relevant to use of the plant in traditional medicine are available. However, decoction of the leaves has been quoted to be used as a remedy for diabetes mellitus and hypertension by villagers living by the sea coast of Western Anatolia. Oral administration of extract for 15 days (50, 150, and 250 mg/kg b.wt.) resulted in a dose-dependent decrease in blood glucose. Relaxant responses to acetylcholine (ACh) in diabetic thoracic aorta were restored by POE treatment (50, 150, and 250 mg/kg b.wt.). POE also attenuated the augmented phenylephrine (PE) and serotonin (5-HT) contractions. At concentration levels of 150 and 250 mg/kg b.wt., POE exerted a protective effect on the significantly decreased levels of antioxidants namely, glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase and nitric oxide (NO). POE (50mg/kg b.wt.) produced no effect on alloxan-induced alterations in the antioxidant status while possessing glucose lowering and vasoprotective activities. Furthermore, liver and kidney function markers, leucocyte counts, body weight and liver glycogen content remained unchanged at dose level of 50mg/kg b.wt., when compared with diabetic control group. These results suggest that antidiabetic and vasoprotective effects of POE may be unrelated to its antioxidant properties.     

Antiinvasive,antiangiogenic and antitumour activity of Ephedra sinica extract

A water fraction (EW), the remaining water phase from the methanol extract of Ephedra sinica after extraction with ethyl acetate and butanol, has been investigated for its antiangiogenic, antiinvasive and antitumour activities. It was observed that EW, at 30 micro g/mL, a non-cytotoxic concentration, inhibited the tube formation induced by human umbilical venous endothelial cells and the invasion of B16F10 melanoma cells through a matrix membrane by more than 90%. At 30 mg/kg/day, the inhibitory activity of EW on the growth of a tumour mass in BDF1 mice inoculated with B16-F10 murine melanoma cells was comparable to that of adriamycin (ADR) administered at 2 mg/kg/day. From these results, it could be postulated that the antitumour activity of the water fraction might be attributed to its antiangiogenic and antiinvasive activities.     

Anti-inflammatory properties of Bridelia ferruginea stem bark. Inhibition of lipopolysaccaride-induced septic shock and vascular permeability

The anti-inflammatory activity of the aqueous extract of Bridelia ferruginea stem bark was further evaluated in models which are mediated by tumour necrosis factor-alpha (TNFalpha). The effect of the extract on lipopolysaccharide (LPS)-induced septic shock was evaluated by measuring the number of deaths and the levels of serum alanine and aspartate aminotransferases following intraperitoneal injection of LPS (1 microg/kg) into D-galactosamine-primed mice. LPS-induced vascular permeability on the back skin of mice was measured by the local accumulation of Evan's blue after subcutaneous injection of LPS. Pre-treatment with Bridelia ferruginea extract (10-80 mg/kg) produced a dose-dependent inhibition of the septic shock syndrome in mice, with 80 mg/kg of the extract exhibiting comparable activity as pentoxifylline (100 mg/kg). LPS-induced dye leakage in the skin of mice was also suppressed by the extract (10-80 mg/kg). Our study suggests that one of the mechanisms of the anti-inflammatory effects of Bridelia ferruginea possibly involve the suppression of TNFalpha up-regulation.     

Evaluation of the radioprotective action of geriforte in mice exposed to different doses of gamma-radiation

The effect of 5, 10, 20, 40 and 80 mg/kg b. wt. of hydroalcoholic extract of geriforte (an Ayurvedic herbal medicine) administered intraperitoneally was studied on the radiation-induced mortality in mice exposed to 10 Gy of gamma-radiation. Treatment of mice with different doses of geriforte consecutively for 5 days before irradiation delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the non-drug treated irradiated controls. A maximum protection was observed for 10 mg/kg geriforte, where a highest number of survivors were reported by 30 days post-irradiation and further experiments were carried out using this dose of geriforte. The mice were treated with 10 mg/kg b. wt. geriforte or double distilled water (DDW) and exposed to 7, 8, 9, 10 and 11 Gy of gamma radiation and observed for the induction of symptoms of radiation sickness and mortality up to 30 days post-irradiation. The geriforte treatment protected the mice against the GI death as well as bone marrow deaths and the dose reduction factor (DRF) was found to be 1.14. Toxicity study showed that geriforte was non-toxic up to a dose of 4250 mg/kg, where no drug-induced mortality was observed. The LD50 dose of geriforte was found to be 4750 mg/kg b. wt. To understand the mechanism of action of geriforte, free radical scavenging activity of the drug was evaluated. Geriforte was found to scavenge *OH, O2*- ABTS*+ and NO* in a dose-dependent manner. Our study demonstrates that geriforte is a good radioprotective agent and the optimum protective dose of 10 mg/kg was 1/475th of the LD50 dose.     

Withania somnifera and Bauhinia purpurea in the regulation of circulating thyroid hormone concentrations in female mice

The effects of daily administration of Withania somnifera root extract (1.4 g/kg body wt.) and Bauhinia purpurea bark extract (2.5 mg/kg body wt.) for 20 days on thyroid function in female mice were investigated. While serum triiodothyronine (T3) and thyroxine (T4) concentrations were increased significantly by Bauhinia, Withania could enhance only serum T4 concentration. Both the plant extracts showed an increase in hepatic glucose-6-phosphatase (G-6-Pase) activity and antiperoxidative effects as indicated either by a decrease in hepatic lipid peroxidation (LPO) and/or by an increase in the activity of antioxidant enzyme(s). It appears that these plant extracts are capable of stimulating thyroid function in female mice.     

Inhibition of clastogenic effects of nicotine by chlorophyllin in mice bone marrow cells in vivo

The effect of chlorophyllin in modifying the clastogenic action of nicotine was tested in vivo on mice bone marrow cells. Nicotine, when administered by gavage, induced chromosomal aberrations in frequencies directly proportional to the dose. Maximum effects were recorded at 6 h after exposure. Chlorophyllin, when given alone, was not clastogenic even at the highest concentration (1.50 mg/kg body wt). Simultaneous administration of nicotine and chlorophyllin with even lower doses (1.25 and 0.77 mg/kg body wt) reduced the frequency of chromosomal aberrations to the normal level. Chlorophyllin alone, given 2 h before nicotine, however, did not counteract the effects of nicotine. The use of green plant parts in modifying the genotoxicity of different agents may be related to the protective action of chlorophyllin.     

Protection by garlic against adriamycin induced alterations in the oxido-reductive status of mouse red blood cells

The effects of oral garlic supplementation on the activities of (a) the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPX) and (b) lipid peroxidation, as assessed by malondialdehyde (MDA) production in red blood cells of normal mice and those subject to oxidative stress by chronic administration of the anti-tumour drug adriamycin has been investigated. As expected, adria-mycin administration resulted in a significant increase in MDA generation (by 105.4%) and a decrease in GPX activity (by 23.8%) in the red blood cells. Although garlic had no significant effects on the basal levels of the antioxidant enzymes or MDA generation in red blood cells of normal mice (untreated with adriamycin), at doses of 20 mg/kg or 100 mg/kg, garlic was able to decrease significantly the adriamycin induced changes in the oxido-reductive status of the red blood cells. Thus, on administration of adriamycin to mice fed diets containing 20 mg/kg or 100 mg/kg garlic, the drug-induced increase in MDA generation was 38.2% and 22.5% respectively, less than that produced by adriamycin in mice fed normal diets, containing no garlic (105.4%). Similarly, in mice fed diets providing 20 mg/kg and 100 mg/kg garlic, adriamycin was able to decrease GPX activity by only 15.1% and 7.6% respectively, less than that produced by adriamycin in rats fed normal diets, containing no garlic (23.9%).     

Polyherbal extract of septilin protects mice against whole body lethal dose of gamma radiation

The effect of various doses (5, 10, 20, 40, 60, 80, 100, 120, 140 and 160 mg/kg b. wt.) of 50% ethanolic extract of Septilin (a herbal preparation) was studied on the radiation-induced mortality in mice exposed to 10 Gy of gamma-irradiation. Treatment of mice with different doses of Septilin, consecutively for 5 days before irradiation, delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the non-drug treated irradiated controls. All doses of Septilin provided protection against gastrointestinal (GI) deaths (death within 10 days of irradiation). However, the best protection was observed at 100 mg/kg b. wt. of Septilin, as the number of survivors after 30 days post-irradiation was highest (58.33%) in this group when compared with the other doses of Septilin. The number of survivors was 1.75 fold greater for 100 mg/kg Septilin when compared with the 2-mercaptopropionylglycine (MPG, 33.33%) which was used as a positive control. The LD(50) of Septilin was 1250 mg/kg as against the optimum protective dose of 100 mg/kg. Our study demonstrates Septilin as a good radioprotective agent.     

Effect of Cuscuta chinensis water extract on 7,12-dimethylbenz[a]anthracene-induced skin papillomas and carcinomas in mice

Cuscuta chinensis, known as Aftimun, is reputed to have antitumour activity in the Unani system of medicine in India. The effect of a hot water extract of C. chinensis on 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin papillomas and carcinomas in Swiss albino mice was studied. Oral administration of the extract (1 g/kg body wt) thrice a week in 22 mice, started on the tenth day after the first application of DMBA to the 252nd day, markedly delayed the appearance and retarded the growth of papillomas and the incidence of carcinoma, relative to a control group with 28 mice, in a two-stage system of tumorigenesis. Its prophylactic effect was found to be statistically significant.