**5. Conclusions**

This study demonstrated that *B. monnieri* active components, including both saponins and flavonoids, produced vasodilatory effects on rat isolated mesenteric arteries partially via endothelial dependent release of vasodilators and also by direct effects on vascular smooth muscle cells via blockade of Ca2<sup>+</sup> influx and its release from SR. This study for the first time reports the comparative vasodilatory effects of saponins and flavonoids found in *B. monnieri* extract. However, *B. monnieri* extract, flavonoids i.e., luteolin and apigenin would be more potent vasodilators but saponins have a greater effect because of their greater contents. Accordingly, the clinical benefits on enhanced blood flow and cognitive function may arise from a combination of flavonoids and particularly the saponins.

**Supplementary Materials:** Supplementary materials are available online. Figure S1: Representative HPLC-UV chromatogram of mixed seven standards at 20 μg/mL for 1 and 2 and 100 μg/mL for 3–7 (A) and Brahmi extract (2 mg/mL) (B); luteolin (1), apigenin (2), bacoside A3 (3), bacopaside II (4), bacopaside X (5), bacopasaponin C (6) and bacopaside I (7), Table S1: Amount of each compound in 95% ethanolic extract of Brahmi analyzed by HPLC.

**Author Contributions:** Conceptualization, K.I., N.W. and K.C.; methodology and experimental design, N.K., T.U.P. and K.C.; software, N.K.; validation, N.K., T.U.P. and K.C.; formal analysis, N.K. and K.C.; investigation, N.K.; resources, K.I., N.W. and K.C.; data curation and interpretation, N.K. and K.C.; writing—original draft preparation, N.K.; manuscript writing—review and editing, T.U.P. and K.C.; visualization, K.I., N.W. and K.C.; supervision, K.I., N.W. and K.C.; project administration, K.C.; funding acquisition, K.C.

**Funding:** This research was funded by National Research Council of Thailand (NRCT), grant No. R2561B032.

**Acknowledgments:** We would like to acknowledge the Center of Excellence for Innovation in Chemistry (PERCH-CIC) and the International Research Network (IRN61W0005) on research facility support. We would like to thank C. Norman Scholfield for his constructive criticism of the manuscript.

**Conflicts of Interest:** The authors declared no conflict of interest.

#### **References**


51. Wisutthathum, S.; Chootip, K.; Martin, H.; Ingkaninan, K.; Temkitthawon, P.; Totoson, P.; Demougeot, C. Vasorelaxant and hypotensive effects of an ethanolic extract of *Eulophia macrobulbon* and Its main compound 1-(4- -hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol. *Front. Pharmacol.* **2018**, *9*, 484. [CrossRef] [PubMed]

**Sample Availability:** Samples of the compounds, luteolin, apigenin, bacoside A and bacopaside I are not available from the authors.

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