Baicalin, a flavonoid from Scutellaria baicalensis Georgi, activates large-conductance Ca2+-activated K+ channels via cyclic nucleotide-dependent protein kinases in mesenteric artery

Lin, Yi-Ling; Dai, Zen-Kong; Lin, Rong-Jyh; Chu, Koung-Shing; Chen, Ing-Jun; Wu, Jiunn-Ren; Wu, Bin-Nan

doi:10.1016/j.phymed.2010.01.003

« Previous Next »Phytomedicine
Volume 17, Issue 10 , Pages 760-770, August 2010

Baicalin, a flavonoid from Scutellaria baicalensis Georgi, activates large-conductance Ca²⁺-activated K⁺ channels via cyclic nucleotide-dependent protein kinases in mesenteric artery

Yi-Ling Lin
- Department of Pharmacology, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Zen-Kong Dai
- Department of Pediatrics, Division of Pediatric Pulmonology and Cardiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Rong-Jyh Lin
- Department of Parasitology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Koung-Shing Chu
- Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Ing-Jun Chen
- Department of Pharmacology, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan
Jiunn-Ren Wu
- Department of Pediatrics, Division of Pediatric Pulmonology and Cardiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Corresponding author at: Department of Pharmacology and Department of Pediatrics, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan. Fax: +88673234686
Bin-Nan Wu
- Department of Pharmacology, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Corresponding author at: Department of Pharmacology and Department of Pediatrics, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan. Fax: +88673234686

published online 19 February 2010.

Abstract

Baicalin isolated from Scutellaria baicalensis is a traditional Chinese herbal medicine used for cardiovascular dysfunction. The ionic mechanism of the vasorelaxant effects of baicalin remains unclear. We investigated whether baicalin relaxes mesenteric arteries (MAs) via large-conductance Ca²⁺-activated K⁺ (BK_Ca) channel activation and voltage-dependent Ca²⁺ channel (VDCC) inhibition. The contractility of MA was determined by dual wire myograph. BK_Ca channels and VDCCs were measured using whole-cell recordings in single myocytes, enzymatically dispersed from rat MAs. Baicalin (10-100μM) attenuated 80mM KCl-contracted MA in a concentration-related manner. L-NAME (30μM) and indomethacin (10μM) little affected baicalin (100μM)-induced vasorelaxations. Contractions induced by iberiotoxin (IbTX, 0.1μM), Bay K8644 (0.1μM) or PMA (10μM) were abolished by baicalin 100μM. In MA myocytes, baicalin (0.3-30μM) enhanced BK_Ca channel activity in a concentration-dependent manner. Increased BK_Ca currents were abolished by IbTX (0.1μM). Baicalin-mediated (30μM) BK_Ca current activation was significantly attenuated by an adenylate cyclase inhibitor (SQ 22536, 10μM), a soluble guanylate cyclase inhibitor (ODQ, 10μM), competitive antagonists of cAMP and cGMP (Rp-cAMP, 100μM and Rp-cGMP, 100μM), and cAMP- and cGMP-dependent protein kinase inhibitors (KT5720, 0.3μM and KT5823, 0.3μM). Perfusate with PMA (0.1μM) abolished baicalin-enhanced BK_Ca currents. Additionally, baicalin (0.3-30μM) reduced the amplitude of VDCC currents in a concentration-dependent manner and abolished VDCC activator Bay K8644-enhanced (0.1μM) currents. Baicalin produced MA relaxation by activating BK_Ca and inhibiting VDCC channels by endothelium-independent mechanisms and by stimulating the cGMP/PKG and cAMP/PKA pathways.