Critical role of high-dose Astragalus in Buyang Huanwu Decoction for enhancing neurovascular coupling in a Qi Deficiency and Blood Stasis animal model.

Overview

1. College of Pharmacy, Changchun University of Chinese Medicine,Changchun, 130012 Jilin China
2. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing, 100050 China
3. Shanxi Key Laboratory of Integrative Systemic Regulation for Qi-Blood Homeostasis, National International Joint Research Center for Molecular Chinese Medicine, Shanxi University of Chinese Medicine,Taiyuan, 030024 China
4. Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Chinese Medicine & Pharmaceutical Science,Nanning, 530022 China

Abstract

Background: Buyang Huanwu Decoction (BHD) is a classical Traditional Chinese Medicine (TCM) formula effective for treating Chronic Cerebral Ischemia with Qi Deficiency and Blood Stasis Syndrome (CCIQDBS), which is known to alleviate neuronal damage and improve cerebral blood flow. The use of a high dose of Astragalus (Huangqi) has been clinically emphasized as crucial to BHD's efficacy, yet the pharmacological basis for this requirement remains unelucidated.

Objective: This study aimed to compare the therapeutic efficacy of BHD with a high dose of Astragalus (120 g, BHDHA) versus a low dose (30 g, BHDLA) in treating CCIQDBS and to investigate the underlying mechanisms.

Methods: A mouse model of CCIQDBS was established by combining systemic hypotension with bilateral common carotid artery occlusion and sleep deprivation. The necessity of high-dose Astragalus in BHD was evaluated by assessing syndrome-specific symptoms, cognitive performance, and brain functional connectivity via functional magnetic resonance imaging (fMRI). Neurovascular coupling (NVC) function was visualized in real-time using two-photon in vivo microscopy. RNA sequencing and immunofluorescence were employed to explore the molecular mechanisms by which BHDHA improves NVC and mitigates brain injury. Finally, the role of nuclear Factor IA (NFIA) was validated through targeted gene silencing using an AAV-shRNA vector (pAVV-U6-shNfia).

Results: BHDHA demonstrated significantly superior therapeutic effects compared to BHDLA. It more effectively ameliorated CCIQDBS-induced deficits, including memory impairment and fatigue-like behaviors, and significantly enhanced brain functional connectivity. Mechanistically, BHDHA induced the morphological recovery of astrocytes, increased their perivascular coverage, and restored impaired NVC function. These beneficial effects were found to be dependent on the upregulation of NFIA. Silencing Nfia abolished the therapeutic advantages of BHDHA in improving NVC and cognitive function.

Conclusion: Our findings demonstrate that the high dose of Astragalus is essential for the therapeutic efficacy of BHD under the conditions of the present experimental model. BHDHA alleviates CCIQDBS by modulating NFIA to maintain the stability of the neurovascular unit (NUV), thereby improving neurovascular coupling, remodeling brain functional connectivity, and restoring cognitive function. This study provides a scientific basis for the high-dose application of Astragalus in this classical formula. This study provides a scientific basis for the high-dose application of Astragalus in the treatment of CCIQDBS using BHD.

Supplementary Information: The online version contains supplementary material available at 10.1186/s13020-026-01443-8.

Reproduced under the paper's license (CC BY), from the paper cited above.

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• figshare:32738119, at figshare; found in DataCite

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 14 authors, 5 keywords, 2 funders, 36 references.

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This paper

Hu, K., Yang, J., Wei, G., Zhao, Y., Chu, S., Li, L., Wang, S., Qu, S., Chen, L., Zhang, Y., Yan, X., Zhang, Z., Chen, N., & He, W. (2026). Critical role of high-dose Astragalus in Buyang Huanwu Decoction for enhancing neurovascular coupling in a Qi Deficiency and Blood Stasis animal model. Chinese medicine, 21(1), 170. https://doi.org/10.1186/s13020-026-01443-8

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