Comparative evaluation of the therapeutic effects of Schisandra chinensis and Schisandra sphenanthera on vascular cognitive impairment and their drug-like compounds

Abstract

The fruits of Schisandra chinensis (SCF) and Schisandra sphenanthera (SSF) are traditional Chinese herbal medicines classified as medicinal and food homologous materials, known for their significant neuroprotective efficacy. However, the differences in their therapeutic effects and active components for the treatment of vascular cognitive impairment (VCI) remain unclear. This study aimed to elucidate the neuroprotective activities of SCF and SSF on VCI and investigate the compositional disparities between the two. The lipopolysaccharide-induced and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced BV2 cell models were used to evaluate the protective effects of SCF and SSF against neuroinflammation and mitochondrial damage, respectively. The therapeutic effects were further validated using a bilateral common carotid artery stenosis mouse model. Compositional differences were analyzed using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), and drug-like properties of their constituents were assessed. In vitro experiments showed that SCF and SSF at concentrations of 6.4, 16, and 40 μg/mL reduced nitric oxide, tumor necrosis factor-alpha, and interleukin-6 levels in a dose-dependent manner. Notably, at the same concentrations, SCF significantly mitigated OGD/R-induced mitochondrial damage, whereas SSF showed no significant effect. Compared with SSF, SCF exhibited stronger anti-neuroinflammatory and antioxidant properties. In vivo experiments further demonstrated that SCF, administered at 400 mg/kg, was more effective in improving learning ability, spatial learning and memory, cerebral blood flow, and nerve fiber repair than SSF. Moreover, 71 and 64 compounds were identified in SCF and SSF, respectively, using UPLC-Q-TOF/MS. Drug-like property analysis of these compounds revealed that the superior therapeutic effects of SCF may be attributed to differences in biphenylcyclooctene-type lignans. Our data support the conclusion that SCF possesses significantly superior neuroprotective activity compared to SSF, providing a theoretical basis for its clinical application in VCI.

Keywords

Schisandra chinensis / Schisandra sphenanthera / Vascular cognitive impairment / Neuroinflammation / Mitochondrial damage / UPLC-Q-TOF/MS

Funding

This work was supported by the CAMS Innovation Fund for Medical Sciences (2023-I2M-QJ-013, 2021-I2M-1-031, 2023-I2M-2-006, and 2022-I2M-2-002), the Beijing Natural Science Foundation (No. Z220019), and National Natural Science Foundation of China (No. U23A20511, No. 82304708).

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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