POTENSI KAVAIN DALAM PIPER METHYSTICUM SEBAGAI TATALAKSANA PREVENTIF GENERALIZED ANXIETY DISORDER
Abstract
Introduction: Generalized Anxiety Disorder (GAD) was a psychiatric disorder characterized by anxiety, motor tension, and autonomic overactivity. Piper methysticum was a plant that had efficacy in various therapies including GAD because of its chemical substance cavaine. Cavaine was a biological ingredient in Piper methysticum which had potent anxiolytic activity. Piper methysticum extract can be used as a preventive therapy for GAD due to its anxiolytic effect on the symptoms of GAD.
Discussion: Piper methysticum in its efficacy was able to potentiate GABAARs without subtype selectivity, besides that the concentration of GABA responds to the performance of 4?2? GABAARs significantly, so that the performance of cavaine works effectively and sensitively in the target system in addition to the 1?2?2L receptor. Cavaine also showed a modest increase in GABA concentrations below EC45, but it did not affect EC50 and maximal efficacy of GABA. In addition, the chalcone synthase chain which is broken due to neurodegeneration by the RpBASi enzyme which can extend a single polypeptide chain can be repaired by cavaine. Another effect of cavaine was that it can modulate volt-gated calcium and sodium channels and antagonize Ca2+ channels. Another important activity of cavaine was being able to bind to GABA receptors in the central nervous system besides functioning as an anxiolytic in the serotonergic and glutamanergic pathways. Piper methysticum in its properties is able to potentiate GABAARs without subtype selectivity, besides that the concentration of GABA responds to the performance of 4?2? GABAARs significantly, so that the performance of cavaine works effectively and sensitively in the target system in addition to the 1?2?2L receptor. Cavaine also showed a modest increase in GABA concentrations below EC45, but it did not affect EC50 and maximal efficacy of GABA. In addition, the chalcone synthase chain which was broken due to neurodegeneration by the RpBASi enzyme which can extend a single polypeptide chain can be repaired by cavaine. Another effect of cavaine, that it was able to modulate volt-gated calcium and sodium channels and acts as an antagonist to Ca2+ channels. Another important activity of cavaine was its ability to bind to GABA receptors in the central nervous system in addition to functioning as anxiolytics in serotonergic and glutamanergic pathways.
Conclusion: The use of Piper methysticum as an effort to prevent GAD has proven to be superior because it was cheap and easy to obtain, had no side effects, and had high effectiveness in reducing GAD in accordance with its effects and clinical features. Therefore, further research on clinical trials of the use of Piper methysticum continues to be developed so that it can be implemented ethically to prevent GAD.
Keywords: Piper methysticum, cavaine, GAD
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References
2. World Health Organization. Noncommunicable Disease Country Profil 2018[Internet]. Geneva: World Health Organization; 2018. Available from: https://www.who.int/nmh/countries/2018/idn_en.pdf?ua=1.
3. Kementerian Kesehatan Republik Indonesia. Penyakit tidak menular (PTM) penyebab kematian terbanyak di Indonesia[Internet]. Kemenkes. 2011 [cited 2021 Oct 5]. Available from: http://www.depkes.go.id/article/print/1637/penyakit-tidak-menular-ptm penyebab-kematian-terbanyak-di-indonesia.html.
4. Ermalena MHS. Indikator sdgs di indonesia. Jakarta: The 4th ICTOH; 2017.
5. Cable News Network. Penyakit Kesehatan Jiwa dalam Perlindungan BPJS[Internet]. Available from: https://www.cnnindonesia.com/gaya-hidup/20181012193101-255-338079/penyakit-kesehatan-jiwa-dalam perlindungan-bpjs.
6. Kementerian Kesehatan Republik Indonesia[Internet].Kemenkes. 2011 [cited 2021 Oct 5]. Available form: http://www.depkes.go.id/article/print/1588/tujuh-kementerian-berkoordinasi-tanggulangi-masalah-kesehatan-jiwa-di-indonesia.html.
7. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-5®). Washington, DC: American Psychiatric Publishing; 2013.
8. American Psychiatric Association (APA). Diagnostic and statistical manual of mental disorders, 5th ed. Arlington: VA APA; 2013.
9. Stein MB, Sareen J. Generalized anxiety disorder. N Engl J Med. 2015;373:2059-68.
10. Kementerian Kesehatan Republik Indonesia. Riset kesehatan dasar indonesia tahun 2018. Jakarta: Kemenkes RI; 2018.
11. Wetherell J, Petkus A, Nguyen H. Antidepressant medication augmented with cognitive-behavioral therapy for generalized anxiety disorder in older adults. Am J Psychiatry. 2013;170:782-9.
12. Revicki D, Travers K, Wyrwich K. Humanistic and economic burden of generalized anxiety disorder in north america and europe. J Affect Disord. 2016;140:103-12.
13. Amir N. Buku ajar psikiatri edisi ke-3. Jakarta: FKUI; 2017.
14. Sadock BJ, Sadock VA, Kaplan HI. Kaplan sadock's synopsis of psychiatry: behavioral sciences/clinical psychiatry. edisi ke-11. Philladelphia: Lippincott Williams & Wilkins; 2018.
15. Spett M. Cognitive-behaviour therapy for panic attacks; 2016 [diperbarui 2016].[diakses pada tanggal 5 Oktober 2021]. Tersedia dari: http://www.njact. org/panic.html.
16. Lebot V, Merlin M, Lindstrom L. Kava: the Pacific drug. New Haven, Connecticut: Yale University Press; 2014.
17. Lebot V, Levesque J. The Origin and distribution and distribution of kava (piper methysticum forst. f, piperaceae) a phytochemical approach, allertonia .national tropical botanical garden. J Lawai Hawaii. 2017;5: 27.
18. Singh YN. Kava: an overview. J Ethnopharmacol. 2014;37:13–45.
19. Mathews JM, Etheridge AS, Valentine JL. Pharmacokinetics and disposition of the kavalactone kavain: interaction with kava extract and kavalactones in vivo and in vitro. Drug Metab Dispos. 2015;33:1555–63.
20. Gleitz J, Beile A, Peters T. (+/−)-Kavain inhibits veratridine-activated voltagedependent Na(+)-channels in synaptosomes prepared from rat cerebral cortex. Neuropharmacol. 2015;34:1133–8.
21. Walden J, von Wegerer J, Winter U. Effects of kavain and dihydromethysticin on field potential changes in the hippocampus. Prog Neuropsychopharmacol Biol Psychiatry. 2017;21:697–706.
22. Uebelhack R, Franke L, Schewe HJ. Inhibition of platelet MAO-B by kavapyrone-enriched extract from Piper methysticum Forster (kava-kava). Pharmacopsychiatry. 1998;31:187–92.
23. Seitz U, Schule A, Gleitz J. [3H]-monoamine uptake inhibition properties of kava pyrones. Planta Med. 1997;63:548–9.
24. Hunot V, Churchill R, Teixeira V, Silva de Lima M. Psychological therapies for generalised anxiety disorder (Review). Cochrane Database of Systematic Reviews. 2016; 24:1848.
25. Etkin, Amit, Prater, Katherine E, Schatzberg, Alan F, et.al. Disrupted amygdalar subregion functional connectivity and evidence of a compensatory network in generalized anxiety disorder. archives of general psychiatry. 2016;66:1361–72.
26. Stahl S. Anxiety disorders and anxiolytics. in: stahl’s essential psychopharmacology, 4th ed. New York: Cambridge University Press, 2013.
27. Sheehan D, Svedsater H, Locklear. Effects of extended-release quetiapine fumarate on long-term functioning and sleep quality in patients with generalized anxiety disorder (gad): data from a randomizedwithdrawal, placebo-controlled maintenance study. J Affect Dis.2013;151:906-13.
28. Chua HC, Absalom NL, Hanrahan JR, Viswas R, Chebib M. The direct actions of GABA, 2'-methoxy-6-methylflavone and general anaesthetics at β3γ2L GABAA receptors: Evidence for receptors with different subunit stoichiometries. PloS one. 2015;10:10-7.
29. Janssen PA, Niemegeers CJ, Schellekens KH, Lenaerts FM. Etomidate, R-(+)-ethyl-1-(α-methyl-benzyl) imidazole-5-carboxylate (R 16659), a potent, short-acting and relatively atoxic intravenous hypnotic agent in rats. Arzneimittel-Forschung. 2013;30:1234-43.
30. Feng HJ, Jounaidi Y, Haburcak M, Yang X, Forman SA. Etomidate produces similar allosteric modulation in α1β3δ and α1β3γ2L GABAA receptors. British Journal of Pharmacology. 2014; 171:789-98.
31. Keledjian J, Duffield PH, Jamieson DD, Lidgard RO, Duffield AM. Uptake into mouse brain of four compounds present in the psychoactive beverage kava. Journal of Pharmaceutical Sciences. 2018;77:1003-6.
32. Mathews JM, Etheridge AS, Valentine JL, Black SR, Coleman DP, Patel P, et. al. Pharmacokinetics and disposition of the kavalactone kawain: interaction with kava extract and kavalactones in vivo and in vitro. Drug Metabolism and Disposition. 2005;33:1555-63.
33. Burbulis IE, Lacobucci M, Shirley BW. A null mutation in the first enzyme of flavonoid biosynthesis does not affect male fertility in Arabidopsis. Plant Cell 8. 2015;2:1013-25.
34. Akiyama T, Shibuya M, Liu HM. Ebizuka Y. p-Coumaroyltriacetic acid synthase, a new homologue of chalcone synthase, from Hydrangea macrophylla var. thunbergii. FEBS J. 2014;263:834-9.
35. Schirrmacher K, Büsselberg D, Langosch JM, Walden J, Winter U. Effects of (+/-)-kavain on voltage-activated inward currents of dorsal root ganglion cells from neonatal rats. Eur Neuropsychopharmacol. 2013;9:171-6.
36. Strahl S, Ehret V, Dahm HH, Maier KP Necrotizing hepatitis after taking herbal remedies. Dtsch Med Wochenschr. 2012; 123:1410-4.
37. Guro RS, Anand P, Hu Q, Mir R. Dermatomyositis-like illness following kava-kava ingestion. J Clin Rheumatol. 2016;5:342-5.
38. Russmann S, Barguil Y, Cabalion P, Kritsanida M, Duhet D. Hepatic injury due to traditional aqueous extracts of kava root in New Caledonia. Eur J Gastroenterol Hepatol. 2014;15:1033-6.
39. Richardson WN, Henderson L. The safety of kava—aregulatory perspective. Br J Clin Pharmacol. 2012;64:418-20.
40. Sarris J, Stough C, Bousman CA, Wahid, Murray ZT, Teschke G, Schweitzer RI. Kava in the Treatment of generalized anxiety disorder. Journal of Clinical Psychopharmacology. 2013;33:643-8.
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