Quote: “The biology lab tucked away in Snyder Hall of Science on the Greenville College campus may look unremarkable, but looks can be deceiving. There, students have discovered a potential key to relief for sufferers of neurological disorders. Their work has drawn international attention.
Juliana Phillips ’17, Kellie Steele ’18 and Michael Shawn Mengarelli ’15 recount their recent discovery in The Journal of Experimental Neuroscience, a peer reviewed international journal. Assistant Professor of Biology Bwarenaba Kautu supervised their work with help from Eric Nord, also assistant professor of biology. … The trio discovered that chemicals in kava seem to affect the transmission of acetylcholine, an important neurotransmitter that is critical to vital functions like cognition, learning and memory, movement, muscle contractions and heartbeat.
“Many psychiatric and neurological disorders have been linked to problems with the transmission of acetylcholine,” Kautu explains. “To the best of my knowledge, our research team is most likely the first in the world to show the link between kava metabolism and acetylcholine transmission in an intact living eukaryotic nervous system (neuromuscular junction). These students are instrumental in this discovery.””
From the paper: “The inhibitory-excitatory balance at the C elegans NMJ is maintained by the opposing actions of GABA and ACh. When the level of ACh signaling (excitation) is substantially greater than the level of GABA transmission (inhibition) at the C elegans NMJ, this results in muscle hypercontraction, which can manifest as a convulsion or paralysis. In our study, we showed that treatment of C elegans with kavalactones resulted in convulsions and paralysis (Figure 1). We hypothesized that these responses are indicative of elevated or prolonged ACh transmission at the NMJ.”
Kava is normally thought of as acting in a GABAergic way, so this result is the opposite of what one would expect.
Interestingly, they noted that kavain has a different effect on worms than the other KLs.
Kautu, Bwarenaba B., et al. “A Behavioral Survey of the Effects of Kavalactones on Caenorhabditis elegans Neuromuscular Transmission.” Journal of experimental neuroscience 11 (2017): 1179069517705384.
Originally posted on Kava Science Forum, April 2017
On another forum, a member asked if it was OK to drink kava while recovering from surgery, due to the possibility that kava could act as a “blood thinner.” This is a summary of the research that I learned about while trying to answer this question. There is not much research on this topic, but there have been a couple scientific papers that suggested kava could act as a “blood thinner” (meaning it could inhibit blood platelets from coagulating, similar to the action of aspirin and other drugs) due to the COX-inhibiting effect of some of it’s constituents.
First, what is “COX?”
Cyclooxygenase, abbreviated to COX, is an enzyme that is involved in the production of prostaglandins and thromboxanes, which are hormone-like chemicals in the body that are involved with blood platelet aggregation (clotting). If the activity of COX is inhibited, it indirectly leads to interference with blood clotting. The most common example of COX inhibiting drugs are non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin and ibuprofen.
(1) The following paper demonstrates that the kavalactones in kava have a COX-inhibiting effect that is similar in magnitude to aspirin or ibuprofen:
“Cyclooxygenase enzyme inhibitory assay-guided purification of ethyl acetate extract of Piper methysticum (kava kava) roots yielded six biologically active compounds (1–7), which were purified using MPLC, preparative TLC and HPLC methods. These compounds were also evaluated for antioxidant activities. Dihydrokawain (1) and yangonin (6) showed the highest COX-I and COX-II inhibitory activities at 100 µg/ml, respectively. The lipid oxidation assay did not reveal antioxidant activities for demethoxyangonin (2), dihydrokawain (1), kawain (4), dihydromethysticin (5) or methysticin (7) at 50 µg/ml. The antioxidant activities of flavokawain A (3) and yangonin (6) could not be tested in the lipid oxidation assay due to solubility problems. However, yangonin and methysticin showed moderate antioxidant activities in the free radical scavenging assay at 2.5 mg/ml. “
This figure from the paper compares the COX inhibiting activities of the kavalactones to ibuprofen, naproxen and aspirin:
Now, what I don’t know is if 100 μg/ml is actually a normally occurring physiological concentration of the chemicals in kava.
(2) This is another paper by the authors of the above paper. They show that other chemicals in kava, in addition to kavalactones, can also inhibit COX, including FKB:
Abstract: “Milled Piper methysticum roots were extracted sequentially with hot water and methanol. Cyclooxygenase (COX) enzyme inhibitory assay directed purification of the methanol extract yielded bornyl esters of 3,4-methylenedioxy cinnamic acid (1) and cinnamic acid (2), pinostrobin (3), flavokawain B (4), and 5,7-dimethoxyflavanone (5). The structures of compounds 1−5 were accomplished by spectral experiments. The aqueous extract contained previously reported kava lactones, as confirmed by TLC analysis. Compounds 3 and 5 were isolated for the first time from kava kava roots. Compound 4 showed the highest COX-I inhibitory activity at 100 μg/mL. All the compounds tested gave good COX-I and moderate COX-II enzyme inhibitory activities at 100 μg/mL. This is the first report of COX-I and -II inhibitory activities for compounds 1−5.”
(3) An older paper specifically about kavain (also concludes that kavain is a COX inhibitor):
Abstract: “(+)-Kavain, a 4-methoxy-alpha-pyrone prepared from Piper methysticum Forst. (Piperaceae), was investigated regarding its assumed antithrombotic action on human platelets which was deduced from its ability to suppress arachidonic acid (AA)-induced aggregation, exocytosis of ATP, and inhibition of cyclooxygenase (COX) and thromboxane synthase (TXS) activity, the latter two effects being estimated from the generation of prostaglandin E2 (PGE2) and thromboxane A2 (TXA2), respectively. Exogenously applied AA (100 mumol/l) provoked a 90% aggregation of platelets, the release of 14 pmol ATP, and the formation of either 220 pg TXA2 or 43 pg PGE2, each parameter being related to 10(6) platelets. An application of (+)-kavain 5 min before AA, dose-dependently diminished aggregation, ATP-release, and the synthesis of TXA2 and PGE2 with IC50 values of 78, 115, 71, and 86 mumol/l, respectively. The similarity of the IC50 values suggest an inhibition of COX by (+)-kavain as primary target, thus suppressing the generation of TXA2 which induces aggregation of platelets and exocytosis of ATP by its binding on TXA2-receptors.”
(4) Also see the following paper about a “TNF‐α” mediated anti-inflammatory activity of kavain and some synthetic derivatives:
Pollastri, Michael P., et al. “Identification and Characterization of Kava‐derived Compounds Mediating TNF‐α Suppression.” Chemical biology & drug design 74.2 (2009): 121-128.
“There is a substantial unmet need for new classes of drugs that block TNF-α-mediated inflammation, and particularly for small molecule agents that can be taken orally. We have screened a library of natural products against an assay measuring TNF-α secretion in lipopolysaccharide (LPS)-stimulated THP-1 cells, seeking compounds capable of interfering with the TNF-α inducing transcription factor Lipopolysaccharide Induced TNF Alpha Factor (LITAF). Among the active compounds were several produced by the kava plant (Piper mysticum), extracts of which have previously been linked to a range of therapeutic effects. When tested in vivo, a representative of these compounds, kavain, was found to render mice immune to lethal doses of LPS. Kavain displays promising pharmaceutical properties, including good solubility and high cell permeability, but pharmacokinetic experiments in mice showed relatively rapid clearance. A small set of kavain analogs was synthesized, resulting in compounds of similar or greater potency in vitro compared to kavain. Interestingly, a ring-opened analog of kavain inhibited TNF-α secretion in the cell based assay and suppressed LITAF expression in the same cells, whereas the other compounds inhibited TNF-α secretion without affecting LITAF levels, indicating a potential divergence in mechanism of action.”