A Chemical and Pharmacological Investigation of Piper Methysticum Forst

Abstract

Piper methysticum Forst. (family Piperaceae) is a shrub common to the islands of Polynesia, where it is known in various dialects as Kawa, Kava or Ava. The root of the kawa plant has been held in high esteem by the Polynesians from ancient times for its use in preparing an extract which, upon drinking, is reported to reduce fatigue and produce complete freedom from anxiety.1The remarkable physiological action of Piper methysticum has prompted numerous chemical investigations, dating from that of Gobley and O'Robke in 1850.2 The most extensive work on the constituents of this plant was carried out by Bobsche3 and his co-workers, who, in a series of 13 papers, reported the isolation and structure of two new compounds, kawain (I)4 and dihydrokawain (II),4 and the structural elucidation of the other crystalline components, methysticin (III),5 dihydromethysticin (IV)6-8' b and yangonin (V),7 which had previously been isolated from this

Survey of 55 Turkish Salvia taxa for their acetylcholinesterase inhibitory and antioxidant activities

“…Our primitive thin layer chromatography (TLC) analysis on the dichloromethane extract of S. fruticosa using 5% sulphuric acid and 1% vanillin as colouring agents pointed out to existence of terpene-like components which appeared as spots in violet-pinkish colours in TLC. It has been proposed that biological activity of plant extracts are usually due to synergistic interaction between components rather than a single compound (Klohs, Keller, & Williams, 1959;Miyazawa, Tougo, & Ishihara, 2001;Savelev, Okello, Perry, Wilkins, & Perry, 2003). Besides, in one of former studies on the same topic (Orhan, Kartal, Kan, & S ßener, 2008), we screened a number of essential oils together with single terpene derivatives, widely found in essential oils (c-terpinene, 4-allyl-anisole, (À)-carvone, dihydrocarvone, (À)-phencone, cuminyl alcohol, cumol, 4-isopropylbenzaldehyde, trans-anethole, camphene, iso-borneol, (À)-borneol, L-bornyl acetate, 2-decanol, 2-heptanol, methyl-heptanol, farnesol, nerol, iso-pulegol, eucalyptol, citral, citronellal, citronellol, geraniol, linalool, a-pinene, b-pinene, piperitone, isomenthone, menthofurane, linalyl oxide, linalyl ester, geranyl ester, carvacrol, thymol, menthol, vanilline, and eugenol) towards AChE and BChE using the same method, and finally came to the point that almost all of the essential oils showed a very high inhibitory activity (over 80%) against both enzymes, whereas the single components were not as active as the essential oils.…”

Piperine-Type Amides: Review of the Chemical and Biological Characteristics

“…Thus, lignans may be formed by oxidative dimerization of the C 6 -C 3 unit, while the piperamides may be derived from the extension of the cinnamic 'starter' unit by increments of C 2 units (malonyl-SCoA). Similarly, it has been suggested that the kavapyrones arise from the cyclisation of the extended phenylpropanoid unit, a process that has been used to synthesise dl-methysticin (Klohs, Keller, William, Teokes, & Cronheim, 1959). The co-occurence of lignans and a number of piperine-type amides, including piperine, in extracts of Piper nigrum (Table 1) is suggestive of a common biogenetic route for these compounds (Grewe, Freist, Neumann, & Kerstein, 1970).…”

Pharmacokinetic and pharmacodynamic drug interactions with Kava (Piper methysticum Forst. f.)

“…The drug screen in this patient was negative for alcohol but positive for benzodiazepines. Prior pharmacological studies, indicating additive effects between kava constituents, pentobarbital and pregnane steroids (Klohs et al, 1959;Meyer, 1962), led these authors to suggest a possible pharmacodynamic interaction between kava and alprazolam. However, the assumption of interactions between kava and alprazolam was criticised by The American Botanical Council (cited in Schmidt, 2003).…”

“…As CYP3A4 is also inhibited by kava and kavalactones (Mathews et al, 2002;Unger et al, 2002;Zou et al, 2002), a pharmacokinetic interaction between alprazolam and kava is another plausible explanation. However, pharmacodynamic interactions might well have occurred, as animal studies with the barbiturates, pentobarbital and hexobarbital, and other non-barbiturate CNS-depressants like urethane and glutethimide suggest synergistic, not simply additive, effects with kavalactones (Klohs et al, 1959;Meyer, 1962). In an early study, Klohs et al (1959) found increased pentobarbital-induced sleeping times (410% compared to controls, groups of at least 10) in mice after oral administration of 60 mg/kg dihydromethysticin.…”