Paeoniflorin Alleviates NG-nitro-L-arginine Methyl Ester (L-NAME)-induced Gestational Hypertension and Upregulates Silent Information Regulator 2 Related Enzyme 1 (SIRT1) to Reduce HO-induced Endothelial Cell Damage

Overview

Journal Bioengineered

Date 2022 Jan 15

PMID 35030965

Authors

Jingjing Wu

Dongmei Zhang

Linlin Hu

Xiaowei Zheng

Caihong Chen

Affiliations

Soon will be listed here.

Abstract

Pregnancy-induced hypertension (PIH) is a leading cause of maternal mortality. Paeoniflorin has been reported to alleviate hypertension, thus relieving the injury of target organ. This study aimed to investigate the role of paeoniflorin in PIH development by regulating SIRT1 in rats. The mean arterial pressure (MAP), urine protein and histopathological damage of placenta in gestational hypertension rats were, respectively, detected by noninvasive tail-artery pressure measuring instrument, BCA method and H&E staining. The viability of human umbilical vein endothelial cells (HUVECs) treated with paeoniflorin or/and HO was observed by CCK-8 assay. SIRT1 protein expression in HUVECs treated with paeoniflorin or/and HO was analyzed by Western blot. Tunel assay, wound healing assay and tube formation assay were used to detect the apoptosis, migration and tube formation of HUVECs administrated with paeoniflorin or/and HO or/and EX527 (SIRT1 inhibitor). As a result, MAP, urine protein and histopathological damage of placenta were enhanced in PIH rats, which were then alleviated by paeoniflorin. Paeoniflorin decreased the levels of sFlt-1, PlGF and VEGF in serum and placental tissues of gestational hypertension rats as well as the inflammatory response and oxidative stress. In addition, paeoniflorin promoted the expressions of SIRT1 and NO/eNOS and inhibited the production of iNOS in gestational hypertension rats to improve vascular endothelial cell injury. However, SIRT1 inhibition could suppress the protective effects of paeoniflorin on endothelial dysfunction of HO-induced HUVECs. In conclusion, paeoniflorin could improve gestational hypertension development by upregulating SIRT1.

Citing Articles

Changes of maternal carotid artery elasticity in patients with pregnancy concurred with hypertension.

Lan Q, Liu S, He Q, Li Y Arch Gynecol Obstet. 2025; .

PMID: 39907747 DOI: 10.1007/s00404-025-07941-8.

Expression of long non-coding RNA GAS5 by first trimester screening predicts the occurrence of gestational hypertension and pre-eclampsia.

Wang L, Chen J, Li H, Zhou Q, Zhang C J Assist Reprod Genet. 2024; 41(6):1661-1667.

PMID: 38530512 PMC: 11224183. DOI: 10.1007/s10815-024-03093-x.

Natural Monoterpenes as Potential Therapeutic Agents against Atherosclerosis.

Yang J, Zhong C, Yu J Int J Mol Sci. 2023; 24(3).

PMID: 36768748 PMC: 9917110. DOI: 10.3390/ijms24032429.

Therapeutic potential of paeoniflorin in atherosclerosis: A cellular action and mechanism-based perspective.

Yu W, Ilyas I, Hu X, Xu S, Yu H Front Immunol. 2023; 13:1072007.

PMID: 36618414 PMC: 9811007. DOI: 10.3389/fimmu.2022.1072007.

Leukotriene Receptor Antagonist, Montelukast Ameliorates L-NAME-Induced Pre-eclampsia in Rats through Suppressing the IL-6/Jak2/STAT3 Signaling Pathway.

Abdelzaher W, Mostafa-Hedeab G, Bahaa H, Mahran A, Fawzy M, Abdel Hafez S Pharmaceuticals (Basel). 2022; 15(8).

PMID: 35893738 PMC: 9332684. DOI: 10.3390/ph15080914.

References

Zhong S, Ge Q, Li Q, Qu R, Ma S . Peoniflorin attentuates Abeta((1-42))-mediated neurotoxicity by regulating calcium homeostasis and ameliorating oxidative stress in hippocampus of rats. J Neurol Sci. 2009; 280(1-2):71-8. DOI: 10.1016/j.jns.2009.01.027. View

Visintin C, Mugglestone M, Almerie M, Nherera L, James D, Walkinshaw S . Management of hypertensive disorders during pregnancy: summary of NICE guidance. BMJ. 2010; 341:c2207. DOI: 10.1136/bmj.c2207. View

Xu K, Zang X, Peng M, Zhao Q, Lin B . Magnesium Lithospermate B Downregulates the Levels of Blood Pressure, Inflammation, and Oxidative Stress in Pregnant Rats with Hypertension. Int J Hypertens. 2020; 2020:6250425. PMC: 7519462. DOI: 10.1155/2020/6250425. View

Liu X, Chen K, Zhuang Y, Huang Y, Sui Y, Zhang Y . Paeoniflorin improves pressure overload-induced cardiac remodeling by modulating the MAPK signaling pathway in spontaneously hypertensive rats. Biomed Pharmacother. 2019; 111:695-704. DOI: 10.1016/j.biopha.2018.12.090. View

Chong Z, Wang S, Shang Y, Maiese K . Targeting cardiovascular disease with novel SIRT1 pathways. Future Cardiol. 2011; 8(1):89-100. PMC: 3254055. DOI: 10.2217/fca.11.76. View

Alma L, de Groot C, de Menezes R, Hermes W, Hordijk P, Kovacevic I . Endothelial dysfunction as a long-term effect of late onset hypertensive pregnancy disorders: High BMI is key. Eur J Obstet Gynecol Reprod Biol. 2018; 225:62-69. DOI: 10.1016/j.ejogrb.2018.04.003. View

Schiessl B, Mylonas I, Hantschmann P, Kuhn C, Schulze S, Kunze S . Expression of endothelial NO synthase, inducible NO synthase, and estrogen receptors alpha and beta in placental tissue of normal, preeclamptic, and intrauterine growth-restricted pregnancies. J Histochem Cytochem. 2005; 53(12):1441-9. PMC: 3957537. DOI: 10.1369/jhc.4A6480.2005. View

Yin Y, Feng Y, Zhao H, Zhao Z, Yua H, Xu J . SIRT1 inhibits releases of HMGB1 and HSP70 from human umbilical vein endothelial cells caused by IL-6 and the serum from a preeclampsia patient and protects the cells from death. Biomed Pharmacother. 2017; 88:449-458. DOI: 10.1016/j.biopha.2017.01.087. View

Lyall F, Bulmer J, Kelly H, Duffie E, Robson S . Human trophoblast invasion and spiral artery transformation: the role of nitric oxide. Am J Pathol. 1999; 154(4):1105-14. PMC: 1866547. DOI: 10.1016/S0002-9440(10)65363-1. View

10.

Yu J, Zhu X, Qi X, Che J, Cao B . Paeoniflorin protects human EA.hy926 endothelial cells against gamma-radiation induced oxidative injury by activating the NF-E2-related factor 2/heme oxygenase-1 pathway. Toxicol Lett. 2013; 218(3):224-34. DOI: 10.1016/j.toxlet.2013.01.028. View

11.

Zhao Y, He X, Ma X, Wen J, Li P, Wang J . Paeoniflorin ameliorates cholestasis via regulating hepatic transporters and suppressing inflammation in ANIT-fed rats. Biomed Pharmacother. 2017; 89:61-68. DOI: 10.1016/j.biopha.2017.02.025. View

12.

He H, Venema V, Gu X, Venema R, Marrero M, Caldwell R . Vascular endothelial growth factor signals endothelial cell production of nitric oxide and prostacyclin through flk-1/KDR activation of c-Src. J Biol Chem. 1999; 274(35):25130-5. DOI: 10.1074/jbc.274.35.25130. View

13.

Say L, Chou D, Gemmill A, Tuncalp O, Moller A, Daniels J . Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014; 2(6):e323-33. DOI: 10.1016/S2214-109X(14)70227-X. View

14.

Giancane G, Alongi A, Ravelli A . Update on the pathogenesis and treatment of juvenile idiopathic arthritis. Curr Opin Rheumatol. 2017; 29(5):523-529. DOI: 10.1097/BOR.0000000000000417. View

15.

Zhang H, Qi Y, Yuan Y, Cai L, Xu H, Zhang L . Paeoniflorin Ameliorates Experimental Autoimmune Encephalomyelitis via Inhibition of Dendritic Cell Function and Th17 Cell Differentiation. Sci Rep. 2017; 7:41887. PMC: 5292961. DOI: 10.1038/srep41887. View

16.

Li B, Yang Z, Lei S, Su J, Pang M, Yin C . Beneficial Effects of Paeoniflorin Enriched Extract on Blood Pressure Variability and Target Organ Damage in Spontaneously Hypertensive Rats. Evid Based Complement Alternat Med. 2017; 2017:5816960. PMC: 5294363. DOI: 10.1155/2017/5816960. View

17.

Dong H, Li R, Yu C, Xu T, Zhang X, Dong M . Paeoniflorin inhibition of 6-hydroxydopamine-induced apoptosis in PC12 cells via suppressing reactive oxygen species-mediated PKCδ/NF-κB pathway. Neuroscience. 2014; 285:70-80. DOI: 10.1016/j.neuroscience.2014.11.008. View

18.

Kim Y, Park H, Lee H, Ha E, Suh S, Oh S . Reduced L-arginine level and decreased placental eNOS activity in preeclampsia. Placenta. 2005; 27(4-5):438-44. DOI: 10.1016/j.placenta.2005.04.011. View

19.

Wang Y, Che J, Zhao H, Tang J, Shi G . Paeoniflorin attenuates oxidized low-density lipoprotein-induced apoptosis and adhesion molecule expression by autophagy enhancement in human umbilical vein endothelial cells. J Cell Biochem. 2018; 120(6):9291-9299. DOI: 10.1002/jcb.28204. View

20.

Li S, Xiong X, Harville E, Zhang T, Sun D, Fernandez C . Childhood Risk Factors and Pregnancy-Induced Hypertension: The Bogalusa Heart Study. Am J Hypertens. 2016; 29(10):1206-11. PMC: 5018998. DOI: 10.1093/ajh/hpw057. View