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. 2021 Nov 8:12:749915.
doi: 10.3389/fphar.2021.749915. eCollection 2021.

Anticonstriction Effect of MCA in Rats by Danggui Buxue Decoction

Ying Guo  1   2 , Yating Zhang  3 , Ya Hou  3 , Pengmei Guo  4 , Xiaobo Wang  4 , Sanyin Zhang  4   5 , Peng Yang  2
Affiliations

Anticonstriction Effect of MCA in Rats by Danggui Buxue Decoction

Ying Guo et al. Front Pharmacol. .

Abstract

Objective: Danggui Buxue decoction (DBD), consisting of Angelicae Sinensis Radix (ASR) and Astragali Radix (AR), is a famous prescription with the function of antivasoconstriction. This study intends to probe its mechanisms on the relaxation of the middle cerebral artery (MCA). Methods: Vascular tension of rat MCA was measured using a DMT620 M system. First, the identical series of concentrations of DBD, ASR, and AR were added into resting KCl and U46619 preconstricted MCA. According to the compatibility ratio, their dilatation effects were further investigated on KCl and U46619 preconstricted vessels. Third, four K+ channel blockers were employed to probe the vasodilator mechanism on KCl-contracted MCA. We finally examined the effects of DBD, ASR, and AR on the vascular tone of U46619-contracted MCA in the presence or absence of Ca2+. Results: Data suggested that DBD, ASR, and AR can relax on KCl and U46619 precontracted MCA with no effects on resting vessels. The vasodilator effect of ASR was greater than those of DBD and AR on KCl-contracted MCA. For U46619-contracted MCA, ASR showed a stronger vasodilator effect than DBD and AR at low concentrations, but DBD was stronger than ASR at high concentrations. Amazingly, the vasodilator effect of DBD was stronger than that of AR at all concentrations on two vasoconstrictors which evoked MCA. The vasodilator effect of ASR was superior to that of DBD at a compatibility ratio on KCl-contracted MCA at low concentrations, while being inferior to DBD at high concentrations. However, DBD exceeded AR in vasodilating MCA at all concentrations. For U46619-constricted MCA, DBD, ASR, and AR had almost identical vasodilation. The dilation of DBD and AR on KCl-contracted MCA was independent of K+ channel blockers. However, ASR may inhibit the K+ channel opening partially through synergistic interactions with Gli and BaCl2. DBD, ASR, and AR may be responsible for inhibiting [Ca2+]out, while ASR and AR can also inhibit [Ca2+]in. Conclusion: DBD can relax MCA with no effects on resting vessels. The mechanism may be related to ASR's inhibition of KATP and Kir channels. Meanwhile, the inhibition of [Ca2+]out by DBD, ASR, and AR as well as the inhibition of [Ca2+]in by ASR and AR may contribute to dilate MCA.

Keywords: Ca2+ channel; Danggui Buxue decoction; K+ channel; middle cerebral artery; vascular tone.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Origin and function of DBD in traditional Chinese medicine. DBD was originally recorded in Differentiation on Endogenous (Neiwaishang Bianhuo Lun, 《内外伤辨惑论》), which was composed of AR and ASR in a ratio of 1:5. DBD ameliorated the deficiency of Qi and blood by tonifying Qi and generating blood, thus treating atherosclerosis, anemia, and diseases related to cerebrovascular injuries. AR, Astragali Radix. ASR, Angelicae Sinensis Radix. DBD, Danggui Buxue decoction.
FIGURE 2
FIGURE 2
Laboratory technology roadmap. After dissection and isolation of the MCA of rats, the changes of DBD, ASR, and AR on the vascular tension were monitored and recorded using the DMT620 M vascular tension detection system. The potential regulatory activities of K+ and Ca2+ channels were further demonstrated to clarify the anticonstriction effect by DBD, ASR, and AR. AR, Astragali Radix. ASR, Angelicae Sinensis Radix. DBD, Danggui Buxue decoction. MCA, middle cerebral artery.
FIGURE 3
FIGURE 3
HPLC analysis of four compounds in lyophilized powder of DBD. Column A represents HPLC chromatograms of standard substances astragaloside IV (A1), ferulic acid (A2), formononetin (A3), and ligustalide (A4). Column B represents HPLC chromatograms of astragaloside IV (B1), ferulic acid, and formononetin (B2) and ligustalide (B3) in lyophilized powder of the DBD sample.
FIGURE 4
FIGURE 4
Effects of serial concentrations of DBD, ASR, and AR (8, 16, 32, 64, 128, and 256 mg/ml) on MCA vessels under resting tension. PSS (control, A), DBD (B), ASR (C), and AR (D) had no effects on resting tension of MCA vessels. DBD, Danggui Buxue decoction. ASR, Angelicae Sinensis Radix. AR, Astragali Radix. MCA, middle cerebral artery.
FIGURE 5
FIGURE 5
Effect of DBD, ASR, and AR on vascular tension of 60 mM KCl precontracted MCA of rats. Diagrams of the effect of cumulative addition of PSS (A), DBD (B), AR (C), and ASR (D) on KCl preconstricted MCA of rats. (E) Comparison of vasodilators by DBD, ARS, and AR on MCA of rats. Data were expressed as the mean ± S.E.M. (n = 5). △ p < 0.05 vs the control group; * p < 0.05 vs the DBD group. DBD, Danggui Buxue decoction. ASR, Angelicae Sinensis Radix. AR, Astragali Radix. MCA, middle cerebral artery.
FIGURE 6
FIGURE 6
Effect of DBD and its compatibility ratio of ASR and AR monotherapy on the regulation of 60 mM KCl precontracted vascular tension. Diagrams of the effect of cumulative addition of DBD (A), ASR (B), and AR (C) on KCl preconstricted MCA of rats. Data were expressed as the mean ± S.E.M. (n = 5). DBD, Danggui Buxue decoction. ASR, Angelicae Sinensis Radix. AR, Astragali Radix. MCA, middle cerebral artery.
FIGURE 7
FIGURE 7
Effect of DBD, ASR, and AR on vascular tension of MCA under 1 μM U46619 precontraction conditions. Diagrams of the effect of cumulative addition of PSS (A), DBD (B), ASR (C), and AR (D) on U46619 preconstricted MCA of rats. (E) Comparison of vasodilators by DBD, ARS, and AR on MCA of rats. Data were expressed as the mean ± S.E.M. (n = 5). △ p < 0.05 vs the control group; * p < 0.05 vs the DBD group. DBD, Danggui Buxue decoction. ASR, Angelicae Sinensis Radix. AR, Astragali Radix. MCA, middle cerebral artery.
FIGURE 8
FIGURE 8
Effect of DBD and its compatibility ratio of ASR and AR monotherapy on vascular tension of MCA under 1 μM U46619 precontraction condition. Diagrams of the effect of cumulative addition of DBD (A), ASR (B), and AR (C) on U46619 preconstricted MCA of rats (D) Comparison of vasodilators by DBD, ARS, and AR on MCA of rats. Data were expressed as the mean ± S.E.M. (n = 5). DBD, Danggui Buxue decoction. ASR, Angelicae Sinensis Radix. AR, Astragali Radix. MCA, middle cerebral artery.
FIGURE 9
FIGURE 9
Regulation of DBD, ASR, and AR on K+ channels. Potentially inhibiting K+ channels opening (TEA, KCa blocker; Gli, KATP blocker; BaCl2, KIR blocker; 4-AP, KV blocker) by DBD (A–D), ASR (E–H), and AR (I–L) on 60 mM KCl precontracted MCA of rats. Statistical results and detailed values of DBD (M), ASR DBD (N), and AR DBD (O) dilating MCA of rats by regulating four kinds of K+ channels. KCa, Ca2+-activated K+ channel. KATP, ATP-sensitive K+ channel. KIR, inwardly rectifer K+ channel. KV, voltage-dependent K+ channel. Data were expressed as the mean ± S.E.M. (n = 5). * p < 0.05 vs the control group. DBD, Danggui Buxue decoction. ASR, Angelicae Sinensis Radix. AR, Astragali Radix. MCA, middle cerebral artery.
FIGURE 10
FIGURE 10
Effect of DBD, ASR, and AR on 1 μM U46619 precontracted MCA of rats by regulation of [Ca2+]out and [Ca2+]in. (A) U46619 contraction of vessels without Ca2+ and secondary contraction of vessels after recalcification. The effect of DBD (B), ASR (C), and AR (D) on vasodilation of MCA in the presence and absence of Ca2+. (E) Statistical results and detailed values of DBD, ASR, and AR on [Ca2+]out and [Ca2+]in. [Ca2+]out, the influx of extracellular Ca2+. [Ca2+]in, the release of internal Ca2+ from organelles. Data were expressed as the mean ± S.E.M. (n = 5). * p < 0.05 vs the control group. DBD, Danggui Buxue decoction. ASR, Angelicae Sinensis Radix. AR, Astragali Radix. MCA, middle cerebral artery.
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