It produces chemopreventive effect by modulating lipid peroxidation and augmenting antioxidant defense system [59, 60]. Supplementation of selleck piperine causes inhibition of Phase I and II enzymes, elevation of glutathione metabolizing enzymes, reduction in DNA damage, and DNA protein cross-links in benzo(a)pyrene-induced lung carcinogenesis in mice [38, 61].The antiapoptotic efficacy of piperine has been demonstrated against cisplatin-induced apoptosis via heme oxygenase-1 induction in auditory cells [62]. Piperine can reverse the corticosterone induced reduction of brain-derived neurotrophic factor mRNA expression in cultured hippocampal neurons [44]. Gallic acid exerts a synergistic effect when administered with piperine and provides a more pronounced therapeutic potential in reducing beryllium-induced hepatorenal dysfunction and oxidative stress consequences [63].

Piperine contains pentacyclic oxindole group which is effective for immunomodulation. This immunomodulation activity is due to its multifaceted activities such as antioxidative, antiapoptotic, and restorative ability against cell proliferative mitogenic response, thymic and splenic cell population, and cytokine release [64].Daily supplement taken with a nutrient or nutrients by an average healthy adult, piperine is effective and safe in a broad dose range. A preferred effective dose range of piperine for oral use to enhance gastrointestinal nutrient absorption is 0.0004�C0.15mg/kg/day. The recommended dose of piperine for a healthy individual for oral use is approximately 5mg/person/day.

Black pepper contains approximately 5�C9% piperine, listed by the Food and Drug Administration (FDA) as an herb which is generally recognized as safe (GRAS) for its intended use as spice, seasoning, or flavoring. The bioenhancing dose of piperine is approximately 15mg/person/day and no more than 20mg/day in divided doses, which corresponds to from several thousands to up to 40,000 times less than the LD50 dose of piperine, as established in various experiments on rodents. The effective bioenhancing dose of piperine for drug compounds varies, but the prior art studies indicated that a dose of approximately 10% (w/w) of the active drug could be regarded as an appropriate bioenhancing dose for most drugs [19]. LD50 of piperine has been found to be 330 and 514mg/kg in mice and rats, respectively. In subacute toxicity tests, piperine in a dosage of 100mg/kg Drug_discovery was found to be nontoxic [65].