Ponemone Venkatesh

Influence of Ginger Rhizome (Zingiber officinale Rosc) on Survival, Glutathione and Lipid Peroxidation in Mice after Whole-Body Exposure to Gamma Radiation

Abstract Jagetia, G. C., Baliga, M. S., Venkatesh, P. and Ulloor, J. N. Influence of Ginger Rhizome (Zingiber officinale Rosc) on Survival, Glutathione and Lipid Peroxidation in Mice after Whole-Body Exposure to Gamma Radiation. Radiat. Res. 160, 584–592 (2003). The radioprotective effect of the hydroalcoholic extract of ginger rhizome, Zingiber officinale (ZOE), was studied. Mice were given 10 mg/kg ZOE intraperitoneally once daily for five consecutive days before exposure to 6–12 Gy of γ radiation and were monitored daily up to 30 days postirradiation for the development of symptoms of radiation sickness and mortality. Pretreatment of mice with ZOE reduced the severity of radiation sickness and the mortality at all doses. The ZOE treatment protected mice from GI syndrome as well as bone marrow syndrome. The dose reduction factor for ZOE was found to be 1.15. The optimum protective dose of 10 mg/kg ZOE was 150 of the LD50 (500 mg/kg). Irradiation of the animals resulted in a dose-dependent elevation in the lipid peroxidation and depletion of GSH on day 31 postirradiation; both effects were lessened by pretreatment with ZOE. ZOE also had a dose-dependent antimicrobial activity against Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli and Candida albicans.

Fruit Extract of Aegle marmelos Protects Mice Against Radiation-Induced Lethality

The radioprotective effect of a hydroalcoholic extracted material from the fruit of Aegle marmelos (AME) was studied in mice exposed to different doses of γ radiation. The optimum dose for radioprotection was determined by administering 0, 5, 10, 20, 40, or 80 mg/kg body weight of AME intraperitoneally (ip) once daily, consecutively for 5 days before exposure to 10 Gy of γ radiation. A total of 20 mg/kg of AME for 5 consecutive days before irradiation was found to afford maximum protection as evidenced by the highest number of survivors after 30 days postirradiation. Animals from all groups were monitored for 30 days postirradiation for development of symptoms of radiation sickness and mortality. Treatment of mice with AME before exposure to different doses of γ radiation reduced the severity of symptoms of radiation sickness and mortality with all exposure doses. This was accompanied by an increase in number of survivors in the AME + irradiation group when compared with the concurrent sterile physiological saline (SPS) + irradiation group. AME pretreatment protected mice against the gastrointestinal as well as bone marrow deaths, as evidenced by the greater number of survivors on day 10 or 30, respectively. LD50/30 was found to be 8.2 Gy for the SPS + irradiation group, while it was 8.8 Gy for AME + irradiation. The dose-reduction factor (DRF) was found to be 1.1 for AME + irradiation group. The acute toxicity study of AME showed that it was nontoxic up to a dose of 6 g/kg body weight, the highest drug dose that could be administered. Irradiation of animals resulted in a dose-dependent elevation in lipid peroxidation in liver, kidney, stomach, and intestine of mice. Conversely, GSH concentration declined in a dose-dependent manner. Treatment of animals with AME before irradiation caused a significant decrease in the lipid peroxidation accompanied by a significant elevation in the GSH concentration in liver, kidney, stomach, and intestine of mice determined at 31 days postirradiation.

Effect of Sapthaparna (Alstonia scholaris Linn) in modulating the benzo(a)pyrene-induced forestomach carcinogenesis in mice

The chemopreventive effect of various doses of hydroalcoholic extract of Alstonia scholaris (ASE) was studied on the benzo(a)pyrene (BaP) induced forestomach carcinoma in female mice. The treatment of mice with different doses, i.e. 1, 2 and 4 mg/ml ASE in drinking water before, during and after the treatment with carcinogen, exhibited chemopreventive activity. The highest activity was observed for 4 mg/ml ASE, where the tumor incidence (93.33%) was reduced by 6.67%. Similarly, the tumor multiplicity reduced (61.29%) significantly (P<0.02) at 4 mg/ml in the pre-post-ASE treated group. However, the pre or post-treatment of mice with 4 mg/ml ASE did not show chemopreventive activity. These findings are corroborated by micronucleus assay, where treatment of mice with ASE before, during and after carcinogen treatment reduced the frequency of micronuclei (MN) in the splenocytes in a dose dependent manner. The MN frequency reached a nadir at 4 mg/ml ASE, the highest drug dose which showed maximum chemopreventive action. The ASE treatment not only reduced the frequency of splenocytes bearing one MN but also cells bearing multiple MN indicating the efficacy of ASE in inhibiting mutagenic changes induced by BaP. The pre or post-treatment of mice with 4 mg/ml ASE also significantly reduced the frequency of BaP-induced MN in the splenocytes of treated animals.

Evaluation of the cytotoxic effect of the monoterpene indole alkaloid echitamine in‐vitro and in tumour‐bearing mice

The cytotoxic effect of various concentrations of echitamine chloride was studied in HeLa, HepG2, HL60, KB and MCF‐7 cell lines in‐vitro and in mice bearing Ehrlich ascites carcinoma (EAC). Exposure of various cells to different concentrations of echitamine chloride resulted in a concentration‐dependent cell killing, and KB cells were found to be most sensitive amongst all the cells evaluated. EAC mice treated with 1, 2, 4, 6, 8, 12 or 16 mgkg−1 echitamine chloride showed a dose‐dependent elevation in the anti‐tumour activity, as evident by increased number of survivors in comparison with the non‐drug treated controls. The highest dose of echitamine chloride (16 mg kg−1) caused toxicity in the recipient mice, therefore 12 mg kg−1 was considered the best cytotoxic dose for its anti‐tumour effect. Administration of 12 mg kg−1 echitamine chloride resulted in an increase in the median survival time (MST) up to 30.5 days, which was 11.5 days higher than the non‐drug treated control (19 days). Administration of 16 mg kg−1 echitamine chloride to EAC mice resulted in a time dependent elevation in lipid peroxidation that reached a peak at 6 h post‐treatment, whereas glutathione concentration declined in a time dependent manner and a maximum decline was reported at 3 h post‐treatment. Our study demonstrated that echitamine chloride possessed anti‐tumour activity in‐vitro and in‐vivo.

Radioprotective Effects of Aegle marmelos (L.) Correa (Bael): A Concise Review

The effective use of radiotherapy in cancer cure and palliation is compromised by the side-effects resulting from radiosensitivity of bordering normal tissues, which are invariably exposed to the cytotoxic effects of ionizing radiation during treatment. In this situation, use of radioprotective compounds that can protect normal tissues against radiation injury are of immense use. In addition to protecting normal tissue these compounds will also permit use of higher radiation doses to obtain better cancer control and possible cure. However, to date, no ideal radioprotectors are available as most synthetic compounds are toxic at their optimal concentrations and have produced little success in clinics. Radiation ill-effects are principally the result of generation of free radicals, and the antioxidant compounds that counter them are supposed to be of immense use in preventing them. In Ayurveda, the traditional Indian system of medicine, several plants have been observed to avert/ameliorate free radical-mediated ailments--an effect that has been documented--and such plants have recently been the focus of attention. Aegle marmelos (L.) Correa (Bael), commonly known as bael, has been used since antiquity for treating various ailments, some of which are now known to be the result of oxidative stress. In studies spanning nearly a decade, it has been observed that bael prevented radiation-induced ill-effects, and the results of these studies indicate that it has the potential to be an effective, nontoxic radioprotective agent. In this current review, for the first time, an attempt is made to summarize these observations and to discuss the plausible reasons responsible for baels radioprotective effects.

Aegle marmelos (L.) Correa (Bael) and Its Phytochemicals in the Treatment and Prevention of Cancer

Aegle marmelos, commonly known as Bael and belonging to the family Rutaceae is an important medicinal plant in the traditional Indian system of medicine, the Ayurveda. The extract prepared by boiling the bark, leaves or roots in water is useful as laxative, febrifuge, and expectorant. The extract is also useful in ophthalmia, deafness, inflammations, catarrh, diabetes, and asthmatic complaints. The fruits are used in treating diarrhea, dysentery, stomach ache, and cardiac ailments. Scientific studies have validated many of Bael’s ethnomedicinal properties and its potential antimicrobial effects, hypoglycemic, astringent, antidiarrheal, antidysenteric, demulcent, analgesic, anti-inflammatory, antipyretic, wound-healing, insecticidal, and gastroprotective properties. In addition, studies have also shown that Bael and some of the Bael phytochemicals possess antineoplastic, radioprotective, chemoprotective, and chemopreventive effects, properties efficacious in the treatment and prevention of cancer. For the first time, the current review summarizes the results related to these properties and emphasizes aspects that require further investigation for Bael’s safe and effective use in the near future.

Polyphenols in the Prevention of Ulcerative Colitis: Past, Present and Future

Ulcerative colitis (UC) is an idiopathic disease of the intestine. The etiology ranges from immune dysfunction, bacterial infiltration, and genetics to environment. Several medications have been employed to treat UC, but most have several side effects. To counter this problem, alternate therapy has been employed, which includes the use of plant-derived phytochemicals that have been investigated. Reports indicate them to be effective in reducing the severity of symptoms associated with UC with concomitant reductions in several markers of inflammation. This chapter deals with polyphenols in the prevention of UC due to their widely accepted benefits and ease of availability. Polyphenols have several applications, ranging from industrial to household and recently in medicine. They have been implicated in the treatment of several diseases and disorders like hypertension, allergies, cancer, diabetes, inflammatory bowel disease, hypercholesterolemia, and several other metabolic and genetic disorders. Several polyphenols, including curcumin and their role in the different pathways leading to the inflammation and pathology of UC, are discussed in this chapter. Curcumin is an active compound found in the turmeric plant and has been found to reduce inflammation, ulcerations and prevent the formation of the pre-cancerous lesions. Clinical trials have shown that curcumin could prevent clinical relapse in patients with inflammatory bowel disease (IBD) with an additional benefit of free radical scavenging leading to reduced oxidative stress. Tea, native to China and Southeast Asia, has several active components like catechins, flavonols, gallic acids and theanine, which were found to be protective against colitis by downregulation of pro-inflammatory cytokines and COX-2. Grape seed polyphenols were also found to be effective in reducing the macroscopic and microscopic lesions of colitis, histological score and reducing translocation of NF-κB in the colon mucosa. Cocoa, another common beverage and the content of chocolate, was found to be protective when co-administered with dextran sodium sulfate (DSS) and decreased colon crypt damage and leucocyte infiltration. Resveratrol is another common polyphenol produced by plants under stress led by pathogenic attack like bacteria and fungi. It is widely accepted for its anti-inflammatory and anti-cancerous effects and has also been found to reduce the pathology of UC. It mediates its protective effects by decreasing neutrophil’s percentage and downregulation of inflammatory markers with reduced myeloperoxidase (MPO) and lipid peroxidation in colon. It is mainly found in the skin of red grapes. Therefore, although the amount in red wine is insignificant, it is available commercially for use as a supplement. Quercetin, silymarin, kaempferol, ellagic acid, and rutoside are some of the other polyphenols discussed in this chapter. They were found to be effective in reducing the pathology and symptoms associated with UC. There are very few studies that indicate the adverse effects of these polyphenols, including the oral administration of 1% green tea polyphenols which increased kidney weight and decreased mRNA expression of HSPs and several antioxidant enzymes. There could be a few exceptions regarding the safety of the use of polyphenols as therapeutic agents in the treatment of UC, and hence more intensive research is needed to declare polyphenols, or any other phytochemicals obtained, as safe for medicinal use. Also, their dosage and the adverse effects of different polyphenols in different disease models need to be established with human studies before the declaration of their use in a particular disease.