Liposome intracellular delivery of Salvia miltiorrhiza Bge. deprivative DS-201 improves its BKCa channel-activating and vasorelaxing effects

Yu, Lei; Cheng, Jun; Huang, Wen‐Jun; Tan, Xiaoqiu; Mao, Liang; Liu, Zhi-Fei; Zeng, Xiaorong; Yang, Yan

doi:10.1007/s11434-016-1046-6

Cited by 4 publications

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References 18 publications

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“…Danshen is a commonly used traditional Chinese medicinal herb, and numbers of studies have been carried out to elucidate the mechanisms ( Cheng, 2007 ; Kim et al, 2007 ; Morton et al, 2015 ; Yu et al, 2016 ). Here we for the first time found a novel mechanism underlying the vasorelaxing effect of DS-201 (a main active derivative of Danshen), i.e., DS-201 inhibited L-type Ca 2+ channel and modulated intracellular Ca 2+ level through complex effects on K + and Ca 2+ channels, and finally reduced the vascular tension.…”

Section: Discussionmentioning

confidence: 99%

“…Large conductance Ca 2+ -activated K + (BK Ca ) channel is the main K + channel in blood vessel for carrying 60-70% of the outward currents, thus it plays a pivotal role in vascular relaxation ( Jaggar et al, 2000 ; Wray et al, 2005 ). We previously reported that DS-201 induced vasodilatation via activating the BK Ca channel in a concentration-dependent manner ( Yang et al, 2008 ; Tan et al, 2011 ; Yu et al, 2016 ). We also found that DS-201 at high concentration (more than 100 μM) decreased BK Ca currents, especially STOCs, suggesting that Ca 2+ -associated action may play a role in the process of BK Ca activity.…”

Section: Introductionmentioning

confidence: 99%

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Sodium Tanshinone II-A Sulfonate (DS-201) Induces Vasorelaxation of Rat Mesenteric Arteries via Inhibition of L-Type Ca2+ Channel

Zhang

Cheng

et al. 2018

Front. Pharmacol.

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Background: We previously have proved that sodium tanshinone II-A sulfonate (DS-201), a derivative of traditional Chinese medicinal herb Danshen (Salvia miltiorrhiza), is an opener and vasodilator of BKCa channel in the vascular smooth muscle cells (VSMCs). Vascular tension is closely associated with Ca2+ dynamics and activation of BKCa channel may not be the sole mechanism for the relaxation of the vascular tension by DS-201. Therefore, we hypothesized that the vasorelaxing effect of DS-20 may be also related to Ca2+ channel and cytoplasmic Ca2+ level in the VSMCs.Methods: Arterial tension was measured by Danish Myo Technology (DMT) myograph system in the mesentery vessels of rats, intracellular Ca2+ level by fluorescence imaging system in the VSMCs of rats, and L-type Ca2+ current by patch clamp technique in Ca2+ channels transfected human embryonic kidney 293 (HEK-293) cells.Results: DS-201 relaxed the endothelium-denuded artery rings pre-constricted with PE or high K+ and the vasorelaxation was reversible. Blockade of K+ channel did not totally block the effect of DS-201 on vasorelaxation. DS-201 suppressed [Ca2+]i transient induced by high K+ in a concentration-dependent manner in the VSMCs, including the amplitude of Ca2+ transient, the time for Ca2+ transient reaching to the [Ca2+]i peak and the time to remove Ca2+ from the cytoplasm. DS-201 inhibited L-type Ca2+ channel with an EC50 of 59.5 μM and at about 40% efficacy of inhibition. However, DS-201did not significantly affect the kinetics of Ca2+ channel. The effect of DS-201 on L-type Ca2+ channel was rate-independent.Conclusion: The effect of DS-201 on vasorelaxation was not only via activating BKCa channel, but also blocking Ca2+ channel and inhibiting Ca2+ influx in the VSMCs of rats. The results favor the use of DS-201 and Danshen in the treatment of cardiovascular diseases clinically.

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