Pharmacokinetic Drug Interactions of Piperine: A Review of Pre-clinical and Clinical Studies.

Piperine (amide alkaloid) derived from pepper is globally utilized in diverse conventional and traditional systems of medicine. The co-administration of piperine has been observed to induce subtle modifications in the absorption, membrane transport, and drug metabolism of several high-efficacy medicines. The occurrence of medication interactions might have a notable impact on the pharmacokinetic parameters, resulting in either a favorable or unfavorable pharmacological effect. This comprehensive pharmacokinetic drug interaction evaluation of piperine encompasses a total of 34 scholarly articles (specific for pharmacokinetic interactions), consisting of 62 studies (56 preclinical studies and 6 clinical investigations). In this study, we propose that piperine has the ability to increase the bioavailability and bioactive molecules of a natural origin of a variety of medications, making it an effective bioenhancer. By enhancing bioavailability, piperine can reduce the required dosage, lower drug costs, minimize the occurrence of drug resistance, and mitigate dose-dependent side effects associated with various medications such as ciprofloxacin, ampicillin, metronidazole carbamazepine, curcumin, and oxytetracycline. However, a limited number of published studies have indicated a reduction in bioavailability following oral administration of isoniazid, puerarin, diltiazem, desacetyldiltiazem, and magnolol in combination with piperine or pepper/Trikatu (containing piperine majorly). Several other critical studies have demonstrated that there is no significant variation in pharmacokinetic characteristics along with piperine. The medications containing piperine have led to significant modifications in their pharmacokinetic properties, finally yielding advantageous outcomes for drugs with low bioavailability. Additionally, these alterations have resulted in reduced side effects and extended half-life (T1/2) for specific drugs.

Beneficial effect of hesperidin on lipopolysaccharide-induced hepatotoxicity.

Hesperidin (HDN) is a flavanone glycoside abundantly found in citrus fruits. HDN has been reported to possess significant activities against allergy, haemorrhoids, hormonal disorders and ulcers. Other reported activities include anti-inflammatory, analgesic, antibacterial, antifungal, antiviral, antioxidant and free radical scavenger activity. A potentially important effect of endotoxin is the increased production of reactive oxygen intermediates as O(2)(-), peroxides and nitric oxide. The study reported here show a beneficial effect of HDN in amelioration of endotoxin-induced hepatic dysfunction and oxidative stress in the liver of rats. Hepatotoxicity was induced by administering lipopolysaccharide (LPS), in a single dose of 1mg/kg intraperitoneally to the rats. A marked hepatic dysfunction evident by rise in serum levels of liver enzymes (ALT, AST, ALP) and total bilirubin (p<0.05) was observed. Serum and tissue nitrite levels were also increased. LPS challenge further increased thiobarbituric acid reactive substances (TBARS) levels, whereas glutathione (GSH) content and superoxide dismutase (SOD) activity were decreased in the liver homogenates of the rats showing a marked oxidative stress. HDN administration successfully and dose dependently attenuated these effects of LPS. In conclusion, these findings suggest that HDN attenuates LPS-induced hepatotoxicity possibly by preventing cytotoxic effects of NO and oxygen free radicals.

Curcumin, a diferuloylmethane, attenuates cyclosporine-induced renal dysfunction and oxidative stress in rat kidneys.

BACKGROUND: In India, Curcumin (CMN) is popularly known as "Haldi", and has been well studied due to its economic importance. Traditional Indian medicine claims the use of its powder against biliary disorders, anorexia, coryza, cough, diabetic wounds, hepatic disorder, rheumatism and sinusitis. This study was designed to examine the possible beneficial effect of CMN in preventing the acute renal failure and related oxidative stress caused by chronic administration of cyclosporine (CsA) in rats. CMN was administered concurrently with CsA (20 mg/kg/day s.c) for 21 days. Oxidative stress in kidney tissue homogenates was estimated using thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) content, superoxide dismutase (SOD), and Catalase (CAT). Nitrite levels were estimated in serum and tissue homogenates. RESULTS: CsA administration for 21 days produced elevated levels of TBARS and marked depletion of renal endogenous antioxidant enzymes and deteriorated the renal function as assessed by increased serum creatinine, Blood Urea Nitrogen (BUN) and decreased creatinine and urea clearance as compared to vehicle treated rats. CMN markedly reduced elevated levels of TBARS, significantly attenuated renal dysfunction increased the levels of antioxidant enzymes in CsA treated rats and normalized the altered renal morphology. CONCLUSION: In conclusion our study showed that CMN through its antioxidant activity effectively salvaged CsA nephrotoxicity.