Polyphenols as anticancer agents: Toxicological concern to healthy cells.

Polyphenols are a group of diverse chemical compounds present in a wide range of plants. Various biological properties such as antiallergic, antiviral, antibacterial, anticarcinogenic, antiinflammatory, antithrombotic, vasodilatory, and hepatoprotective effect of different polyphenols have been reported in the scientific literature. The major classes of polyphenols are flavonoids, stilbenoids, lignans, and polyphenolic acids. Flavonoids are a large class of food constituents comprising flavones, isoflavanones, flavanones, flavonols, catechins, and anthocyanins sub-classes. Even with seemingly broad biological activities, their use is minimal clinically. Among the other concurrent problems such as limited bioavailability, rapid metabolism, untargeted delivery, the toxicity associated with these polyphenols has been a topic of concern lately. These polyphenols have been reported to result in different forms of toxicity that include organ toxicity, genotoxicity, mutagenicity, cytotoxicity, etc. In the present article, we have tried to unravel the toxicological aspect of these polyphenols to healthy cells. Further high-quality studies are needed to establish the clinical efficacy and toxicology concern leading to further exploration of these polyphenols.

Hepato-protective effect of Allium sativum against immobilization stress in rats.

The purpose of the current study was to examine immobilization stress-induced antioxidant defense changes and estimation of the antioxidant potential of pre and post stress treatment of aqueous garlic extract in rat's liver. For this purpose, male Albino Wistar rats were treated with aqueous garlic extract both pre and after 6 h of immobilization stress. Pro-oxidant status of rat liver was evaluated by determining the levels of reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), glucose, uric acid and the activities of super oxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST). In response to 6 h of immobilization stress a significant rise in the level of above mentioned liver enzymes were recorded. However, SOD, CAT and GST enzymatic activities showed a sharp decline. The extract treatment before and after stress, almost reverted the activities of studied biochemical parameters towards their control values. Current study highlighted the antioxidant potential of garlic extracts. Based on our study, we recommend the use of garlic extract as nutritional supplement for combating oxidative stress induced damage.

Garlic extract attenuates immobilization stress-induced alterations in plasma antioxidant/oxidant parameters and hepatic function in rats.

OBJECTIVE: To investigate the oxidative stress induced by 6 h of immobilization stress in Albino Wistar rats. Further, the pre- and post-treatment of aqueous garlic extract was studied to evaluate its preventive and curative efficacy on stress-induced altered oxidative parameters in rats. METHODS: Albino Wistar rats were exposed to 6 h of immobilization stress, and received garlic extract (100 mg/kg body weight) treatment pre- or post-stress exposure. The oxidative status of plasma after various treatments were evaluated by determining the levels of reduced glutathione, glucose, uric acid, thiobarbituric acid reactive substances, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and the activities of superoxide dismutase, catalase and glutathione-S-transferase by standardized procedures. RESULTS: Immobilization of rats generated oxidative stress in rat plasma, by decreasing the activities of antioxidant enzymes, glutathione levels and glucose, while increasing the lipid peroxidation, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, ALP and uric acid compared to the non-stressed controls (P<0.01). The garlic extract administration both pre- and post-stress exposure significantly prevented the rise in the diagnostic liver enzymes and reverted the decrease of antioxidant enzymatic activities compared to the stressed group (P<0.05 or P <0.01). Post-stress treatment of extract was found more effective than pre-stress treatment in reverting the values back to normal (P<0.01). CONCLUSION: Garlic extract seems promising as a nutritional supplement for scavenging free radicals generated in the plasma and to prevent resulting oxidative stress.

Chronic unpredictable stress deteriorates the chemopreventive efficacy of pomegranate through oxidative stress pathway.

Chronic unpredictable stress (CUS) can influence the risk and progression of cancer through increased oxidative stress. Pomegranate is known to protect carcinogenesis through its anti-oxidative properties. This study is carried out to examine whether CUS affects the chemopreventive potential of pomegranate through oxidative stress pathway. Role of CUS on early stages of 7, 12 dimethyl benz(a) anthracene (DMBA) induced carcinogenesis, and its pre-exposure effect on chemopreventive efficacy of pomegranate juice (PJ) was examined in terms of in vivo antioxidant and biochemical parameters in Swiss albino rats. Rats were divided in various groups and were subjected to CUS paradigm, DMBA administration (65 mg/kg body weight, single dose), and PJ treatment. Exposure to stress (alone) and DMBA (alone) led to increased oxidative stress by significantly decreasing the antioxidant enzymes activities and altering the glutathione (GSH), malondialdehyde (MDA), glutamate oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT) levels. A significant increase in DNA damage demonstrated by comet assay was seen in the liver cells. Stress exposure to DMBA-treated rats further increased the oxidative stress and disturbed the biochemical parameters as compared to DMBA (alone)-treated rats. Chemoprevention with PJ in DMBA (alone)-treated rats restored the altered parameters. However, in the pre-stress DMBA-treated rats, the overall antioxidant potential of PJ was significantly diminished. Our results indicate that chronic stress not only increases the severity of carcinogenesis but also diminishes the anti-oxidative efficacy of PJ. In a broader perspective, special emphasis should be given to stress management and healthy diet during cancer chemoprevention.

Protective Effect of Solanum nigrum Leaves Extract on Immobilization Stress Induced Changes in Rat's Brain.

The prophylactic or curative antioxidant efficacy of crude extract and the active constituent of S. nigrum leaves were evaluated in modulating inherent antioxidant system altered due to immobilization stress in rat brain tissues, in terms of measurement of glutathione (GSH), lipid peroxidation (thiobarbituric acid reactive substances, TBARS), and free radical scavenging enzymes activities. Rats were treated with single dose of crude extract of S. nigrum prior to and after 6 h of immobilization stress exposure. Exposure to immobilization stress resulted in a decrease in the brain levels of glutathione, SOD, GST, and catalase, with an increase in thiobarbituric acid reactive substances (TBARS) levels. Treatment of S. nigrum extract and its active constituents to both pre- and poststressed rats resulted in significant modulation in the above mentioned parameters towards their control values with a relative dominance by the latter. Brain is vulnerable to stress induced prooxidant insult due to high levels of fat content. Thus, as a safe herbal medication the S. nigrum leaves extract or its isolated constituents can be used as nutritional supplement for scavenging free radicals generated in the brain due to physical or psychological stress or any neuronal diseases per se.