POTENSI KAVAIN DALAM PIPER METHYSTICUM SEBAGAI TATALAKSANA PREVENTIF GENERALIZED ANXIETY DISORDER
Abstrak
Pendahuluan: Generalized Anxiety Disorder (GAD) merupakan gangguan psikiatri yang ditandai dengan kecemasan, ketegangan motorik, dan overaktivitas autonomik. Piper methysticum merupakan tumbuhan yang memiliki khasiat dalam berbagai terapi termasuk GAD karena senyawa kavain sebagai substansi kimiawinya. Kavain merupakan kandungan biologis dalam Piper methysticum yang memiliki aktivitas ansiolitik poten. Ekstrak Piper methysticum dapat digunakan sebagai terapi preventif GAD terkait dengan kemampuannya dalam efek ansiolitik mengatasi gejala dari GAD.
Pembahasan: Piper methysticum dalam khasiatnya mampu untuk mempotensiasi GABAARs tanpa selektivitas subtipe, selain itu konsentrasi GABA merespon kinerja ?4?2? GABAARs secara signifikan, sehingga kinerja kavain bekerja secara efektif dan sensitif dalam sistem target disamping pada reseptor ?1?2?2L. Kavain juga menunjukkan peningkatan sederhana pada konsentrasi GABA di bawah EC45, tetapi tidak memengaruhi EC50 dan kemanjuran maksimal GABA. Selain itu rantai kalkon sintase yang terputus akibat adanya neurodegenerasi oleh enzim RpBASi yang dapat memperpanjang rantai polipeptida tunggal dapat diperbaiki oleh kavain. Efek kavain lainnya adalah kavain mampu memodulasi saluran kalsium juga natrium volt-gated dan berperan antagonis terhadap saluran Ca2+. Aktivitas penting lain dari kavain yaitu mampu mengikat reseptor GABA dalam sistem saraf pusat disamping berfungsi sebagai ansiolitik di jalur serotonergik dan glutamanergik.
Simpulan: Penggunaan Piper methysticum sebagai upaya preventif GAD terbukti unggul karena murah dan mudah didapatkan, tidak ada efek samping, serta memiliki efektivitas tinggi dalam menurunkan GAD yang sesuai dengan efek dan fitur klinisnya. Oleh karena itu, penelitian lebih lanjut mengenai uji klinis penggunaan Piper methysticum terus dikembangkan agar dapat diimplementasikan secara etis untuk mencegah GAD.
Kata kunci: Piper methysticum, kavain, GAD
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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.
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.
Diterbitkan
2022-07-20
##submission.howToCite##
MAHENDIKA, Devin.
POTENSI KAVAIN DALAM PIPER METHYSTICUM SEBAGAI TATALAKSANA PREVENTIF GENERALIZED ANXIETY DISORDER.
Essence of Scientific Medical Journal, [S.l.], v. 20, n. 1, p. 27-34, july 2022.
ISSN 2655-6472.
Tersedia pada: <http://103.29.196.112/index.php/essential/article/view/78348>. Tanggal Akses: 04 mar. 2026
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