The role of salvianolic acid B and benzoylpaeoniflorin in enhancing angiogenesis through Nrf2/HO-1/VEGFA signaling axis in ischemic stroke recovery

Sep 30, 2026

Uploaded by Melati

Angiogenesis supports neural repair and regeneration after ischemic stroke, and salvianolic acid B (SAB) and benzoylpaeoniflorin (BP), derived from Salvia miltiorrhiza and Paeonia suffruticosa, are investigated for their combined pro-angiogenic effects. The study evaluates SAB-BP in a middle cerebral artery occlusion rat model, a ponatinib-induced zebrafish ischemic model, and oxygen-glucose deprivation/reperfusion human umbilical vein endothelial cells. Neuroprotection is assessed by behavioral and histopathology assays, while angiogenesis is measured via zebrafish thrombosis and endothelial functional assays plus Nrf2/HO-1/VEGFA protein analyses. SAB-BP promotes functional vessel formation and up-regulates Nrf2, HO-1, HIF-1α, and VEGFA, with inhibition by an Nrf2 blocker.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Abstract

Introduction

Materials and methods

Results

Discussion and conclusion

Keywords

Pharmaceutical Biology 2026, Vol. 64, No. 1, 67–86 [https://doi.org/10.1080/13880209.2025.2605571](https://doi.org/10.1080/13880209.2025.2605571) ReseaRch aRticle The role of salvianolic acid B and benzoylpaeoniflorin in enhancing angiogenesis through Nrf2/HO-1/VEGFA signaling axis in ischemic stroke recovery chao Zhaoa,b\#, Xiaodan Baic\#, Yi Dinga, aiguo Zengb, aidong Wena, Qiang Fub,d and Jingwen Wanga aDepartment of Pharmacy, Xijing hospital, Fourth military medical university, Xi’an, china; bDepartment of Pharmaceutical analysis, School of Pharmacy, Xi’an Jiaotong university, Xi’an, china; cDepartment of Pharmacy, tangdu hospital, Fourth military medical university, Xi’an, china; dDepartment of Pharmaceutical analysis, college of Pharmacy, Shenzhen technology university, Shenzhen, china ABSTRACT Context: angiogenesis is one of the essential protective mechanisms that promote neural repair and regeneration after ischemic stroke (is). salvianolic acid B (saB) and Benzoyl paeoniflorin (BP) are compounds extracted from the chinese medicines Salvia miltiorrhiza Bunge and Paeonia suffruticosa andrews, respectively. Objective: We investigated whether saB combined with BP alleviated is by promoting micrangium angiogenesis and determined the potential molecular mechanisms. Materials and methods: the impact of saB-BP on angiogenesis after is was investigated in middle cerebral artery occlusion (McaO) rat model, ponatinib-induced ischemic stroke in zebrafish, and human umbilical vein endothelial cells (hUVecs). the neuroprotective effect of saB-BP in rats was assessed using behavior tests and histopathological staining. the cerebral thrombosis assessment and angiogenesis assay were performed in the zebrafish model. cell proliferation and angiogenesis in oxygen-glucose deprivation andreperfusion (OGD/R) hUVecs were assessed through cell viability, tube formation, migration, and invasion assays. Western blot analysis and immunofluorescence staining were used to determine the protein expression levels of Nrf2, hO-1, and VeGFa. Results: the findings indicated that saB-BP significantly reduced neurological impairment following is and promoted the formation of functional vessels in the cerebral ischemic penumbra. Furthermore, saB-BP up-regulated the protein expression of Nrf2, hO-1, hiF-1α, and VeGFa. intriguingly, the pro-angiogenic effect of saB-BP markedly restrained by adding the inhibitor of Nrf2 (Ml385). Discussion and conclusion: Our study demonstrates that saB-BP enhances angiogenesis following is by modulating the Nrf2/hO-1/VeGFa signaling axis both in vivo and in vitro. saB-BP could serve as a promising therapeutic agent for is recovery. Introduction ARTICLE HISTORY received 21 august 2025 revised 8 December 2025 accepted 12 December 2025 KEYWORDS Salvianolic acid B; benzoylpaeoniflorin; ischemic stroke; angiogenesis; Nrf2/ho-1/ VegFa signaling axis Ischemic stroke (IS), resulting from disrupted cerebral blood flow, causes major neural damage and is a leading global cause of death and disability (Caplan 1991) . The management of IS has traditionally focused on the early reperfusion of at-risk tissue through intravenous thrombolysis and/or endovascular thrombectomy. However, surgical thrombectomy may paradoxically exacerbate ischemia-reperfusion injury, thereby worsening cerebral damage (Krishnan et al. 2021) . Tissue plasminogen activator is the only FDA-approved drug for IS, but its use is limited by a short therapeutic window, reduced effectiveness, and potential for causing hemorrhagic complications. Increased microvessel density in the peri-infarct region indicates that angiogenesis regulation is vital for neural repair and regeneration after IS (Kanazawa et al. 2019; Fang et al. 2023) . CONTACT Jingwen Wang [wangjingwen8021@163.com](wangjingwen8021@163.com) Department of Pharmacy, Xijing hospital, Fourth military medical university, No. 127 West changle road, Xincheng District, Xi’an ci

FAQs

What is the main objective of this study on SAB and BP?

To determine whether salvianolic acid B combined with benzoylpaeoniflorin alleviates ischemic stroke by promoting microvascular angiogenesis and to identify underlying molecular mechanisms.

Which experimental models are used to test the effects of SAB-BP?

A middle cerebral artery occlusion rat model, a ponatinib-induced ischemic stroke zebrafish model, and oxygen-glucose deprivation/reperfusion-treated human umbilical vein endothelial cells are used.

How does SAB-BP influence the Nrf2/HO-1/VEGFA signaling axis?

SAB-BP up-regulates Nrf2, HO-1, HIF-1α, and VEGFA protein expression, and its pro-angiogenic effect is reduced by the Nrf2 inhibitor ML385.

Sep 30, 2026

Uploaded by Melati