Endothelium-dependent and endothelium-independent vasorelaxant effects of tiliacorinine 12'-O-acetate and mechanisms on isolated rat aorta

Luckika Panthiya; Rungusa Pantan; Jiraporn Tocharus; Archawin Nakaew; Apichart Suksamrarn; Chainarong Tocharus

doi:10.1016/j.biopha.2018.11.062

Endothelium-dependent and endothelium-independent vasorelaxant effects of tiliacorinine 12'-O-acetate and mechanisms on isolated rat aorta

Biomed Pharmacother. 2019 Jan:109:2090-2099. doi: 10.1016/j.biopha.2018.11.062. Epub 2018 Nov 26.

Authors

Luckika Panthiya¹, Rungusa Pantan¹, Jiraporn Tocharus², Archawin Nakaew³, Apichart Suksamrarn⁴, Chainarong Tocharus⁵

Affiliations

¹ Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
² Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
³ Department of Chemistry and Center of Excellence of Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok, 10240, Thailand.
⁴ Department of Chemistry and Center of Excellence of Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok, 10240, Thailand. Electronic address: s_apichart@ru.ac.th.
⁵ Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Center for Research and Development of Natural Products for Health, Chiang Mai University, Chiang Mai, 50200, Thailand. Electronic address: chainarong.t@cmu.ac.th.

PMID: 30551466
DOI: 10.1016/j.biopha.2018.11.062

Abstract

Tiliacorinine 12'-O-acetate is a modified analog of Tiliacorinine, a major compound in Tiliacora triandra. The present study explored the vasorelaxation property of tiliacorinine 12'-O-acetate and its mechanism in isolated rat aorta using the organ bath technique. Tiliacorinine 12'-O-acetate exhibited concentration-dependent (10^-15-10^-3.5 M) vasorelaxation in endothelium-intact rings (E_max = 93.53 ± 2.79%) and endothelium-denuded rings (E_max = 74.31 ± 5.09%). The effects of tiliacorinine 12'-O-acetate were attenuated by pre-incubation with N(ω)-nitro-l-arginine methyl ester (L-NAME, endothelium nitric oxide synthase inhibitor) (100 μM), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, soluble quanylylcyclase inhibitor) (1 μM), and 4-aminopyridine (1 mM, K_v channel blocker). However, this effect was not impacted by indomethacin (10 μM, cyclooxygenase inhibitor), tetraethylammonium (5 mM, K_ca channel blocker), barium chloride (1 mM, K_IR channel blocker), or glibenclamide (10 μM, K_ATP channel blocker). Moreover, pretreatment with tiliacorinine 12'-O-acetate reduced the effect of L-NAME (100 μM) on acetylcholine-induced vasorelaxation. Tiliacorinine 12'-O-acetate showed inhibitory effects on CaCl₂-induced contracted rings and reduced the contraction induced by phenylephrine (10 μM) and caffeine (20 mM) in a Ca²⁺-free solution. The results of this study suggest that tiliacorinine 12'-O-acetate induced endothelium-dependent vasorelaxation through the eNOS/NO/sGC pathway, and also induced endothelium independent vasorelaxation involving the modulation of sGC activity, K_v channels, Ca²⁺ influx through Ca²⁺ channels and intracellular Ca²⁺ release. The data concerning the benefits of tiliacorinine 12'-O-acetate might be further investigated for the application of tiliacorinine 12'-O-acetate as an antihypertensive compound.

Keywords: Endothelium-dependent; Endothelium-independent; Hypertension; Tiliacorinine 12′-O-acetate; Vasorelaxant effect.

Publication types

Comparative Study

MeSH terms

Acetic Acid / chemical synthesis
Acetic Acid / pharmacology*
Animals
Aorta, Thoracic / drug effects*
Aorta, Thoracic / physiology
Benzylisoquinolines / chemical synthesis
Benzylisoquinolines / pharmacology*
Dose-Response Relationship, Drug
Endothelium, Vascular / drug effects*
Endothelium, Vascular / physiology
Male
Organ Culture Techniques
Rats
Rats, Wistar
Vasodilation / drug effects*
Vasodilation / physiology
Vasodilator Agents / pharmacology*

Substances

Benzylisoquinolines
Vasodilator Agents
tiliacorinine
Acetic Acid