In vitro Na+/K+-ATPase inhibitory activity and antimicrobial activity of sesquiterpenes isolated from Thujopsis dolabrata

Abstract

A series of sesquiterpenes and hinokitiol-related compounds (1-15) was isolated from the essential oil of Thujopsis dolabrata Sieb. et Zucc. var. hondai Makino, and their structures were determined by combined spectroscopic analyses. The inhibitory effects of these compounds on microbial cell growth and Na(+)/K(+)-ATPase were evaluated in vitro. It was found that (-)-elema-1,3,11(13)-trien-12-ol (5), α,β,γ-costol (8), and chamigrenol (11) inhibit the activities of Na(+)/K(+)-ATPase, with IC(50) values of 11.2 ± 0.11, 12.2 ± 0.09, and 15.9 ± 0.54 μg/mL, respectively. Thujopsene (1), cedrol (9), γ-cuparenol (10), and chamigrenol (11) showed potent antibacterial activity, with MIC values in the range of 25-50 μg/mL, and β-thujaplicin (12) exhibited a broad spectrum of antibacterial and antifungal activity. These results indicate that these isolated compounds are promising candidates for the development of potent Na(+)/K(+) ATPase inhibitors and antimicrobial agents.

Mast Cell Stabilizing Effect of (−)-Elema-1,3,11(13)-trien-12-ol and Thujopsene from <i>Thujopsis dolabrata</i> Is Mediated by Down-Regulation of Interleukin-4 Secretion in Antigen-Induced RBL-2H3 Cells

“…MeOH), then further purified by reversed-phase HPLC (55% aq. MeCN) to afford 11.6 mg and 14.3 of (−)-elema-1,3,11(13)-trien-12-ol (1) 30) and thujopsene-12-ol (3), 27) respectively. The aliquot (551 mg) of the fraction eluted with 100% nhexane from flash chromatography was separated by silica HPLC (YMC-silica, 100% n-hexane), then further purified by reversed-phase HPLC (YMC ODS-A column, 1 cm×25 cm, 5% aq.…”

“…The aliquot (551 mg) of the fraction eluted with 100% nhexane from flash chromatography was separated by silica HPLC (YMC-silica, 100% n-hexane), then further purified by reversed-phase HPLC (YMC ODS-A column, 1 cm×25 cm, 5% aq. MeOH) to afford 451.4 and 14.3 mg of thujopsene (2) 27) and cuparene (4), 27) respectively. Finally an aliquot (289 mg) of the fraction eluted with 30% EtOAc in n-hexane from flash chromatography was separated by reversed-phase HPLC (25% aq MeOH) to afford 5.3, 6.1, 7.4 mg of (−)-elema-1,3,11(13)-trien-12-ol (1), thujopsene-12-ol (3), and γ-cuparenol (5), 27) respectively.…”

“…MeOH) to afford 451.4 and 14.3 mg of thujopsene (2) 27) and cuparene (4), 27) respectively. Finally an aliquot (289 mg) of the fraction eluted with 30% EtOAc in n-hexane from flash chromatography was separated by reversed-phase HPLC (25% aq MeOH) to afford 5.3, 6.1, 7.4 mg of (−)-elema-1,3,11(13)-trien-12-ol (1), thujopsene-12-ol (3), and γ-cuparenol (5), 27) respectively. Based upon the results of combined spectroscopic analysis and comparison of the Cell Culture The Rat basophilic leukemia (RBL-2H3) cells (ATCC No.…”

“…27) In our previous study, it was reported that essential oil from Thujopsis dolobrata reduced both serum levels of histamine and IgE in atopic dermatitis (AD)-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) in NC/Nga mice, and furthermore it presented a mast cell stabilizing effect by inhibiting the release of β-hexosaminidase from antigen-induced RBL-2H3 mast cells. 29) In present study, two compounds, (−)-elema-1,3,11(13)-trien-12-ol (1) and thujopsene (2) isolated from essential oil of Thujopsis dolabrata were investigated for the inhibition of mast cell degranulation, IL-4 secretion, and IL-4 mRNA and protein expression in antigen-induced RBL-2H3 mast cells.…”

“…26) (−)-Elema-1,3,11(13)-trien-12-ol (1) has been reported that (−)-elema-1,3,11(13)-trien-12-ol (1) has inhibitory effects on Na + /K + -ATPase activity 27) and inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production, 28) and thujopsene (2) has antibacterial activity. 27) In our previous study, it was reported that essential oil from Thujopsis dolobrata reduced both serum levels of histamine and IgE in atopic dermatitis (AD)-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) in NC/Nga mice, and furthermore it presented a mast cell stabilizing effect by inhibiting the release of β-hexosaminidase from antigen-induced RBL-2H3 mast cells.…”