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At least 361 records · Page 20Linked to original sources
PubMed1998

Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava).

Kava-kava, a psychoactive beverage, induces relaxation, improves social interaction, promotes sleep and plays an important role in the sociocultural life in the islands of the South Pacific. On the other hand, standardized extracts of kava-kava roots are used for the therapy of anxiety, tension and restlessness. Kava pyrones, the major constituents of kava kava, are generally considered to be responsible for the pharmacological activity in humans and animals. To obtain more information on the mechanisms by which kava-kava exerts psychotropic properties we investigated the in vitro effects of kava-kava extract and pure synthetic kava pyrones on human platelet MAO-B, in comparison to amitriptyline, imipramine and brofaromine. Kava-kava extract was found to be a reversible inhibitor of MAO-B in intact platelets (IC50 24 microM) and disrupted platelet homogenates (IC50 1.2 microM). Structural differences of kava pyrones resulted in a different potency of MAO-B inhibition. The order of potency was desmethoxyyangonin > (+/-)-methysticin > yangonin > (+/-)-dihydromethysticin > (+/-)- dihydrokavain > (+/-)-kavain. The two most potent kava pyrones, desmethoxyyangonin and (+/-)-methysticin displayed a competetive inhibition pattern with mean Ki 0.28 microM and 1.14 microM respectively. The inhibition of MAO-B by kava pyrone-enriched extracts might be an important mechanism for their psychotropic activity.

Amitriptyline↗
PubMed2006

Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans.

Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC((0-3)), AUC((0-24)), CL/F, t(1/2), and C(max), whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C(max) (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo.

Adult↗
PubMed2003

He who pays the piper calls the tune: the role of the industry sponsor in acute stroke trials.

Ischemic stroke remains a complex neurobiological and clinical disease, and stroke drug development remains time consuming and costly. In addressing these challenges, the pharmaceutical industry has a principal responsibility to ensure that the acute stroke trials it sponsors are ethically conducted, scientifically sound and satisfy global regulatory requirements. The industry must also be a leader in promoting the innovative and effective partnerships between the public, private and academic sectors that are necessary if new therapies for patients with acute stroke are to be developed.

Acute Disease↗
PubMed1991

Carcinogenic effect of force-feeding an extract of black pepper (Piper nigrum) in Egyptian toads (Bufo regularis).

50 male and 50 female Bufo regularis were treated, by force-feeding, with an extract of black pepper, at a dose level of 2 mg, 3 times a week for 5 months. The first tumors appeared after 2 months. Liver tumors (hepatocellular carcinomas, lymphosarcomas and fibrosarcomas) were found in 12 males and 18 females. Metastatic deposits of hepatocellular carcinomas were registered in the spleen, kidney, fat body and ovary.

Animals↗