Pretreatment with β-Boswellic Acid Improves Blood Stasis Induced Endothelial Dysfunction: Role of eNOS Activation.
Vascular endothelial cells play an important role in modulating anti-thrombus and maintaining the natural function of vascular by secreting many active substances. β-boswellic acid (β-BA) is an active triterpenoid compound from the extract of boswellia serrate. In this study, it is demonstrated that β-BA ameliorates plasma coagulation parameters, protects endothelium from blood stasis induced injury and prevents blood stasis induced impairment of endothelium-dependent vasodilatation. Moreover, it is found that β-BA significantly increases nitric oxide (NO) and cyclic guanosine 3', 5'-monophosphate (cGMP) levels in carotid aortas of blood stasis rats. To stimulate blood stasis-like conditions in vitro, human umbilical vein endothelial cells (HUVECs) were exposed to transient oxygen and glucose deprivation (OGD). Treatment of β-BA significantly increased intracellular NO level. Western blot and immunofluorescence as well as immunohistochemistry reveal that β-BA increases phosphorylation of enzyme nitric oxide synthase (eNOS) at Ser1177. In addition, β-BA mediated endothelium-dependent vasodilatation can be markedly blocked by eNOS inhibitor L-NAME in blood stasis rats. In OGD treated HUEVCs, the protective effect of β-BA is attenuated by knockdown of eNOS. In conclusion, the above findings provide convincing evidence for the protective effects of β-BA on blood stasis induced endothelial dysfunction by eNOS signaling pathway.
Department of pharmacy, Xijing Hospital, Fourth Military Medical University, Shaanxi, Xi'an 710032, China.|Shaanxi University of Chinese Medicine, Shaanxi, Xian-yang 712046, China.
Mingming
M
Wang
Department of pharmacy, Xijing Hospital, Fourth Military Medical University, Shaanxi, Xi'an 710032, China.
Minchun
M
Chen
Department of pharmacy, Xijing Hospital, Fourth Military Medical University, Shaanxi, Xi'an 710032, China.
Yi
Y
Ding
Department of pharmacy, Xijing Hospital, Fourth Military Medical University, Shaanxi, Xi'an 710032, China.
Zhihui
Z
Zhu
Department of pharmacy, Xijing Hospital, Fourth Military Medical University, Shaanxi, Xi'an 710032, China.
Yikai
Y
Zhang
Shaanxi University of Chinese Medicine, Shaanxi, Xian-yang 712046, China.
Peifeng
P
Wei
Department of pharmacy, Xijing Hospital, Fourth Military Medical University, Shaanxi, Xi'an 710032, China.
Jingwen
J
Wang
Department of pharmacy, Xijing Hospital, Fourth Military Medical University, Shaanxi, Xi'an 710032, China.
Yi
Y
Qiao
Department of pharmacy, Xijing Hospital, Fourth Military Medical University, Shaanxi, Xi'an 710032, China.
Liang
L
Li
Department of pharmacy, Xijing Hospital, Fourth Military Medical University, Shaanxi, Xi'an 710032, China.
Yuwen
Y
Li
Department of pharmacy, Xijing Hospital, Fourth Military Medical University, Shaanxi, Xi'an 710032, China.
Aidong
A
Wen
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010101:Oxygen Consumption; D010766:Phosphorylation; D051381:Rats; D014315:Triterpenes / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014315:Triterpenes; D009569:Nitric Oxide; C054625:boswellic acid; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP; D005947:Glucose