Vasodilatory Effect of <i>n</i>-Butanol Extract from <i>Sanguisorba officinalis</i> L. and Its Mechanism
The dried root of <i>Sanguisorba officinalis</i> L. (commonly known as Diyu) has been studied for its various pharmacological effects, including its antibacterial, antitumor, antioxidant, and anti-inflammatory activities. In the present study, primary cultured vascular endothelial cells...
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2025-04-01
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| author | Hangyu Jin Jiaze Li Shuyuan Wang Enyi Jin Jun Zhe Min Gao Li Yun Jung Lee Lihua Cao |
| author_facet | Hangyu Jin Jiaze Li Shuyuan Wang Enyi Jin Jun Zhe Min Gao Li Yun Jung Lee Lihua Cao |
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| description | The dried root of <i>Sanguisorba officinalis</i> L. (commonly known as Diyu) has been studied for its various pharmacological effects, including its antibacterial, antitumor, antioxidant, and anti-inflammatory activities. In the present study, primary cultured vascular endothelial cells (HUVECs) and isolated phenylephrine-precontracted rat thoracic aortic rings were examined to investigate the possible mechanism of a butanol extract of Diyu (BSO) in its vascular relaxant effect. HUVECs treated with BSO produced a significantly higher amount of nitric oxide (NO) compared to the control. However, its production was inhibited by pretreatment with N<sup>G</sup>-nitro-L-arginine methylester (L-NAME) or wortmannin. BSO also increased the phosphorylation levels of endothelial nitric oxide synthase (eNOS) and Akt. In the aortic ring, BSO relaxed PE-precontracted rat thoracic aortic rings in a concentration-dependent manner. The absence of the vascular endothelium significantly attenuated BSO-induced vasorelaxation. The non-selective NOS inhibitor, L-NAME, and the selective inhibitor of soluble guanylyl cyclase (sGC), 1H-[1,2,4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ), dramatically inhibited the BSO-induced relaxation effect of the endothelium-intact aortic ring. Ca<sup>2+</sup>-free buffer and intracellular Ca<sup>2+</sup> homeostasis regulators (TG, Gd<sup>3+</sup>, and 2–APB) inhibited BSO-induced vasorelaxation. In Ca<sup>2+</sup>-free Krebs solution, BSO markedly reduced PE-induced contraction. Vasodilation induced by BSO was significantly inhibited by wortmannin, an inhibitor of Akt. Pretreatment with the non-selective inhibitor of Ca<sup>2+</sup>-activated K<sup>+</sup> channels (K<sub>Ca</sub>), tetraethylammonium (TEA), significantly attenuated the BSO-induced vasorelaxant effect. Furthermore, BSO decreased the systolic blood pressure and heart rate in a concentration-dependent manner in rats. In conclusion, BSO induces vasorelaxation via endothelium-dependent signaling, primarily through the activation of the PI3K-Akt-eNOS-NO signaling pathway in endothelial cells, and the activation of the NO-sGC-cGMP-K⁺ channels pathway in vascular smooth muscle cells. Additionally, store-operated Ca<sup>2+</sup> entry (SOCE)-eNOS pathways and the inhibition of Ca<sup>2</sup>⁺ mobilization from intracellular stores contribute to BSO-induced vasorelaxation. |
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| spelling | doaj-art-9e7531b63dbf4bec9a0f374b039a9ced2025-08-20T03:08:53ZengMDPI AGPlants2223-77472025-04-01147109510.3390/plants14071095Vasodilatory Effect of <i>n</i>-Butanol Extract from <i>Sanguisorba officinalis</i> L. and Its MechanismHangyu Jin0Jiaze Li1Shuyuan Wang2Enyi Jin3Jun Zhe Min4Gao Li5Yun Jung Lee6Lihua Cao7Clinical Medicine, College of Medicine, Yanbian University, Yanji 133002, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Medical Pharmacy, Yanbian University, Yanji 133002, ChinaCenter of Morphological Experiment, College of Medicine, Yanbian University, Yanji 133002, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Medical Pharmacy, Yanbian University, Yanji 133002, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Medical Pharmacy, Yanbian University, Yanji 133002, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Medical Pharmacy, Yanbian University, Yanji 133002, ChinaWonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan 54538, Republic of KoreaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Medical Pharmacy, Yanbian University, Yanji 133002, ChinaThe dried root of <i>Sanguisorba officinalis</i> L. (commonly known as Diyu) has been studied for its various pharmacological effects, including its antibacterial, antitumor, antioxidant, and anti-inflammatory activities. In the present study, primary cultured vascular endothelial cells (HUVECs) and isolated phenylephrine-precontracted rat thoracic aortic rings were examined to investigate the possible mechanism of a butanol extract of Diyu (BSO) in its vascular relaxant effect. HUVECs treated with BSO produced a significantly higher amount of nitric oxide (NO) compared to the control. However, its production was inhibited by pretreatment with N<sup>G</sup>-nitro-L-arginine methylester (L-NAME) or wortmannin. BSO also increased the phosphorylation levels of endothelial nitric oxide synthase (eNOS) and Akt. In the aortic ring, BSO relaxed PE-precontracted rat thoracic aortic rings in a concentration-dependent manner. The absence of the vascular endothelium significantly attenuated BSO-induced vasorelaxation. The non-selective NOS inhibitor, L-NAME, and the selective inhibitor of soluble guanylyl cyclase (sGC), 1H-[1,2,4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ), dramatically inhibited the BSO-induced relaxation effect of the endothelium-intact aortic ring. Ca<sup>2+</sup>-free buffer and intracellular Ca<sup>2+</sup> homeostasis regulators (TG, Gd<sup>3+</sup>, and 2–APB) inhibited BSO-induced vasorelaxation. In Ca<sup>2+</sup>-free Krebs solution, BSO markedly reduced PE-induced contraction. Vasodilation induced by BSO was significantly inhibited by wortmannin, an inhibitor of Akt. Pretreatment with the non-selective inhibitor of Ca<sup>2+</sup>-activated K<sup>+</sup> channels (K<sub>Ca</sub>), tetraethylammonium (TEA), significantly attenuated the BSO-induced vasorelaxant effect. Furthermore, BSO decreased the systolic blood pressure and heart rate in a concentration-dependent manner in rats. In conclusion, BSO induces vasorelaxation via endothelium-dependent signaling, primarily through the activation of the PI3K-Akt-eNOS-NO signaling pathway in endothelial cells, and the activation of the NO-sGC-cGMP-K⁺ channels pathway in vascular smooth muscle cells. Additionally, store-operated Ca<sup>2+</sup> entry (SOCE)-eNOS pathways and the inhibition of Ca<sup>2</sup>⁺ mobilization from intracellular stores contribute to BSO-induced vasorelaxation.https://www.mdpi.com/2223-7747/14/7/1095<i>Sanguisorba officinalis</i>DiyuvasorelaxationNO-cGMPK<sup>+</sup> channelsPI3K-Akt |
| spellingShingle | Hangyu Jin Jiaze Li Shuyuan Wang Enyi Jin Jun Zhe Min Gao Li Yun Jung Lee Lihua Cao Vasodilatory Effect of <i>n</i>-Butanol Extract from <i>Sanguisorba officinalis</i> L. and Its Mechanism Plants <i>Sanguisorba officinalis</i> Diyu vasorelaxation NO-cGMP K<sup>+</sup> channels PI3K-Akt |
| title | Vasodilatory Effect of <i>n</i>-Butanol Extract from <i>Sanguisorba officinalis</i> L. and Its Mechanism |
| title_full | Vasodilatory Effect of <i>n</i>-Butanol Extract from <i>Sanguisorba officinalis</i> L. and Its Mechanism |
| title_fullStr | Vasodilatory Effect of <i>n</i>-Butanol Extract from <i>Sanguisorba officinalis</i> L. and Its Mechanism |
| title_full_unstemmed | Vasodilatory Effect of <i>n</i>-Butanol Extract from <i>Sanguisorba officinalis</i> L. and Its Mechanism |
| title_short | Vasodilatory Effect of <i>n</i>-Butanol Extract from <i>Sanguisorba officinalis</i> L. and Its Mechanism |
| title_sort | vasodilatory effect of i n i butanol extract from i sanguisorba officinalis i l and its mechanism |
| topic | <i>Sanguisorba officinalis</i> Diyu vasorelaxation NO-cGMP K<sup>+</sup> channels PI3K-Akt |
| url | https://www.mdpi.com/2223-7747/14/7/1095 |
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