title: Ursolic acid enhances pentobarbital-induced sleeping behaviors via GABAergic neurotransmission in mice.
abstract: Prunella vulgaris is widely used as a herbal medicine for cancers, inflammatory diseases, and other infections. Although it has long been used, few studies have examined its effects on central nervous system function. Here, we first observed that ethanolic extracts of P. vulgaris (EEPV) prolonged pentobarbital-induced sleep duration in mice. It is known that EEPV consists of many active components including triterpenoid (ursolic acid and oleanolic acid), which have many biological activities. Therefore, we evaluated which EEPV components induced sleep extension in pentobarbital-mediated sleeping model in mice. Surprisingly, despite their structural similarity and other common functions such as anti-inflammation, anti-cancer, and tissue protection, only ursolic acid enhanced sleep duration in pentobarbital-treated mice. These results were attenuated by bicuculline treatment, which is a GABAA receptor antagonist. The present results suggest that ursolic acid from P. vulgaris enhances sleep duration through GABAA receptor activation and could be a therapeutic candidate for insomnia treatment.
authors.affiliation: Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Kyunghee-daero 26, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jeon
authors.affiliation: Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Kyunghee-daero 26, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Kyunghee-daero 26, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Kyunghee-daero 26, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Qingtao
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Department of Pharmacy, Sahmyook University, Seoul 139-742, Republic of Korea.
authors.forename: Irene Joy Dela
authors.initials: IJ
authors.lastname: Pena
authors.affiliation: Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Kyunghee-daero 26, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Kyunghee-daero 26, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Kyunghee-daero 26, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Kyunghee-daero 26, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Hyung Eun
authors.initials: HE
authors.lastname: Lee
authors.affiliation: Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Kyunghee-daero 26, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Kyunghee-daero 26, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Woo
authors.affiliation: Department of Pharmacy, Sahmyook University, Seoul 139-742, Republic of Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, Sahmyook University, Seoul 139-742, Republic of Korea.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Cheong
authors.affiliation: Natraceutical & Functional Foods Center, CJ Foods R&D, Seoul 152-051, Republic of Korea.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Hong
authors.affiliation: Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Kyunghee-daero 26, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea; Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Kyunghee-daero 26, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Kyunghee-daero 26, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea. Electronic address: jhryu63@khu.ac.kr.
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Ryu
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D058256:Brain Waves / Q000187:drug effects; D000431:Ethanol / Q000737:chemistry; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010424:Pentobarbital / Q000494:pharmacology*; D031347:Prunella / Q000737:chemistry; D011963:Receptors, GABA-A / Q000378:metabolism; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000431:Ethanol; D058787:GABA-A Receptor Antagonists; D010424:Pentobarbital; D011963:Receptors, GABA-A; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: GABA(A) receptor; Prunella vulgaris; Sleep; Triterpenoid; Ursolic acid