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Buqi Huoxue Tongnao prescription protects against chronic cerebral hypoperfusion via regulating PI3K/AKT and LXRα/CYP7A1 signaling pathways.
Gao, Yinhuang; Zhao, Peng; Wang, Chunyan; Fang, Keren; Pan, Yueqing; Zhang, Yan; Miao, Zhishuo; Wang, Meirong; Wei, Minlong; Zou, Wei; Liu, Menghua; Peng, Kang.
Afiliación
  • Gao Y; Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Peng Kang National Famous Traditional Chinese Medicine Expert Inheritance Studio, Southern Medicine University, Guangzhou 510315, China; Key Laboratory of Drug Metabolism Research and Evaluation of the State
  • Zhao P; Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Peng Kang National Famous Traditional Chinese Medicine Expert Inheritance Studio, Southern Medicine University, Guangzhou 510315, China.
  • Wang C; Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Peng Kang National Famous Traditional Chinese Medicine Expert Inheritance Studio, Southern Medicine University, Guangzhou 510315, China.
  • Fang K; Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Peng Kang National Famous Traditional Chinese Medicine Expert Inheritance Studio, Southern Medicine University, Guangzhou 510315, China.
  • Pan Y; Key Laboratory of Drug Metabolism Research and Evaluation of the State Drug Administration, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
  • Zhang Y; Key Laboratory of Drug Metabolism Research and Evaluation of the State Drug Administration, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
  • Miao Z; Key Laboratory of Drug Metabolism Research and Evaluation of the State Drug Administration, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
  • Wang M; Key Laboratory of Drug Metabolism Research and Evaluation of the State Drug Administration, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
  • Wei M; Key Laboratory of Drug Metabolism Research and Evaluation of the State Drug Administration, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
  • Zou W; Changsha Research and Development Center on Obstetric and Gynecologic Traditional Chinese Medicine Preparation, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan 410008, China.
  • Liu M; Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Peng Kang National Famous Traditional Chinese Medicine Expert Inheritance Studio, Southern Medicine University, Guangzhou 510315, China; Key Laboratory of Drug Metabolism Research and Evaluation of the State
  • Peng K; Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Peng Kang National Famous Traditional Chinese Medicine Expert Inheritance Studio, Southern Medicine University, Guangzhou 510315, China. Electronic address: Pkang12@smu.edu.cn.
Phytomedicine ; 132: 155844, 2024 Sep.
Article en En | MEDLINE | ID: mdl-38959552
ABSTRACT

BACKGROUND:

Chronic cerebral hypoperfusion (CCH) has been confirmed as one of the pathogenesis underlying vascular cognitive impairment. A series of pathological changes, including inflammation, oxidative stress, and apoptosis, are involved in this pathophysiology and contribute to cognitive impairment and neuropathological alterations. The traditional Chinese medicine (TCM) of Buqi Huoxue Tongnao (BQHXTN) prescription possesses a remarkable clinical efficacy for treating patients with CCH, but still lacks a scientific foundation for its pharmacological mechanisms.

PURPOSE:

To investigate the role and underlying mechanism of the effects of BQHXTN on CCH both in vitro and in vivo.

METHODS:

In this study, we established a two-vessel occlusion (2-VO) induced CCH model in Sprague-Dawley rats, an oxygen-glucose deprivation model in BV2 cells, and a steatosis cell model in L02 cells to reveal the underlying mechanisms of BQHXTN by behavioral test, histopathological analysis and the detection of pro-inflammatory cytokine, apoptotic factors and reactive oxide species. Donepezil hydrochloride and Buyang Huanwu decoction were used as positive drugs.

RESULTS:

Compared with the 2-VO group, BQHXTN treatment at three doses significantly enhanced the memory and learning abilities in the Y-maze and novel object recognition tests. The hematoxylin-eosin staining indicated that BQHXTN protected against hippocampal injury induced by CCH. Of note, in both in vivo and in vitro experiments, BQHXTN prominently inhibited the production of IL-1ß, TNF-α, cleaved-caspase 3, and iNOS by regulating the PI3K/AKT pathway, consequently exerting anti-inflammatory, anti-apoptotic, and antioxidant effects. Moreover, it provided the first initial evidence that BQHXTN treatment mitigated dyslipidemia by increasing the LXRα/CYP7A1 expression, thereby delaying the neuropathological process.

CONCLUSION:

In summary, these findings firstly revealed the pharmacodynamics and mechanism of BQHXTN, that is, BQHXTN could alleviate cognitive impairment, neuropathological alterations and dyslipidemia in CCH rats by activating PI3K/AKT and LXRα/CYP7A1 signaling pathways, as well as providing a TCM treatment strategy for CCH.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Medicamentos Herbarios Chinos / Transducción de Señal / Ratas Sprague-Dawley / Fosfatidilinositol 3-Quinasas / Proteínas Proto-Oncogénicas c-akt / Receptores X del Hígado Límite: Animals Idioma: En Revista: Phytomedicine Asunto de la revista: TERAPIAS COMPLEMENTARES Año: 2024 Tipo del documento: Article Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Medicamentos Herbarios Chinos / Transducción de Señal / Ratas Sprague-Dawley / Fosfatidilinositol 3-Quinasas / Proteínas Proto-Oncogénicas c-akt / Receptores X del Hígado Límite: Animals Idioma: En Revista: Phytomedicine Asunto de la revista: TERAPIAS COMPLEMENTARES Año: 2024 Tipo del documento: Article Pais de publicación: Alemania