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Inflammopharmacology

Erschienen in:

27.07.2019 | Original Article

Betulinic acid attenuates lipopolysaccharide-induced vascular hyporeactivity in the rat aorta by modulating Nrf2 antioxidative function

verfasst von: Yao-Yao Bai, Dong Yan, Hui-Ying Zhou, Wei-Xin Li, Yang-Yun Lou, Xin-Ru Zhou, Ling-Bo Qian, Chi Xiao

Erschienen in: Inflammopharmacology | Ausgabe 1/2020

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Abstract

Betulinic acid (BA), a pentacyclic triterpenoid, has been reported to inhibit cardiovascular dysfunction under sepsis-induced oxidative stress. Nuclear factor erythroid-2 related factor-2 (Nrf2) is regarded as a key transcription factor regulating expression of endogenous antioxidative genes. To explore the preventive effects of BA against vascular hyporeactivity and the related antioxidative mechanism in sepsis, contraction and relaxation in aortas isolated from lipopolysaccharide (LPS)-challenged rats were performed. Male Sprague–Dawley rats were pretreated with brusatol (Bru, 0.4 mg/kg/2 days, i.p.), an inhibitor of Nrf2, and BA (10, 25, 50 mg/kg/day, i.g.) for 3 days and injected with LPS (10 mg/kg, i.p.) at the 4th day. Rats were anesthetized and killed by cervical dislocation after they were treated with LPS for 4 h. Thoracic aortas were immediately dissected out to determine contraction and relaxation using the organ bath system. Pro-inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) and oxidative stress were measured in aortic tissues and plasma. mRNA expression of Nrf2-regulated antioxidative enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and heme oxygenase-1 (HO-1), in rat aortas was determined. Increases of IL-1β, TNF-α, nitric oxide, and malondialdehyde and the decrease of glutathione induced by LPS were significantly attenuated by pretreatment with different doses of BA in plasma and aortas (p < 0.05 versus LPS), all of which were blocked by Bru (p < 0.01). Inhibition of phenylephrine (PE)- and KCl-induced contractions and acetylcholine (ACh)-induced vasodilatation in aortas from LPS-challenged rats was dose-dependently reduced by BA (p < 0.05; percentage improvements by BA in PE-induced contraction were 55.38%, 96.41%, and 104.33%; those in KCl-induced contraction were 15.11%, 23.96%, and 22.96%; and those in ACh-induced vasodilatation were 16.08%, 42.99%, and 47.97%), all of which were reversed by Bru (p < 0.01). Improvements of SOD, GPx, and HO-1 mRNA expression conferred by BA in LPS-challenged rat aortas were inhibited by Bru (p < 0.01; 145.45% versus 17.42%, 160.69% versus 22.76%, and 166.88% versus 23.57%). These findings suggest that BA attenuates impairments of aortic contraction and relaxation in LPS-challenged rats by activating Nrf2-regulated antioxidative pathways.

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Titel: Betulinic acid attenuates lipopolysaccharide-induced vascular hyporeactivity in the rat aorta by modulating Nrf2 antioxidative function
verfasst von: Yao-Yao Bai
Dong Yan
Hui-Ying Zhou
Wei-Xin Li
Yang-Yun Lou
Xin-Ru Zhou
Ling-Bo Qian
Chi Xiao
Publikationsdatum: 27.07.2019
Verlag: Springer International Publishing
Erschienen in: Inflammopharmacology / Ausgabe 1/2020
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-019-00622-4

Springer Medizin

Abstract

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