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Global Translational Medicine Comparative study of Schisandra species on VCI

2 The National Clinical Research Center for Mental Disorders and Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital
and Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China

1. Introduction stroke, Alzheimer’s disease, and Parkinson’s disease. 16-20 In
contrast, research on SSF remains relatively limited. It is
Vascular cognitive impairment (VCI) refers to a clinical unclear whether SCF and SSF exhibit significant therapeutic
syndrome characterized by the impairment of at least one effects against VCI. The differences in pharmacological
cognitive function domain, caused by cerebrovascular efficacy and contributing constituents between SCF and
disease and its associated risk factors. It encompasses SSF are also uncertain.
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a broad spectrum of cognitive disorders, ranging from
mild cognitive impairment to dementia. The prevalence In this study, we evaluated the therapeutic differences
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of VCI increases rapidly with age, making it the second between SCF and SSF in VCI using in vivo and in vitro
most prevalent type of cognitive deficit after Alzheimer’s models, characterized their chemical composition through
disease. The primary symptoms of VCI, including attention ultraperformance liquid chromatography-quadrupole
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deficits, memory loss, language impairment, executive time-of-flight mass spectrometry (UPLC-Q-TOF/
dysfunction, and spatial cognitive decline, significantly MS), and evaluated the drug-like properties of their
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impact patients’ quality of life. Although studies have components. The findings aim to provide valuable insights
shown that medications, such as donepezil can benefit into the pharmacological difference of SCF and SSF against
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VCI patients, their clinical efficacy remains contentious. VCI and offer a reference for their clinical applications.
This underscores the imperative for developing safe and
effective therapeutic agents for VCI. 2. Materials and methods
Traditional Chinese medicine (TCM) has attracted 2.1. Cell culture
growing attention owing to its efficacy in the prevention and BV2 cells were cultured in Dulbecco’s Modified Eagle
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treatment of VCI. More importantly, TCM is recognized Medium (DMEM) supplemented with 10% fetal bovine
for its safety and effectiveness, especially in managing serum (Gibco, USA). Cells at 80% – 90% confluence
chronic conditions. Wuweizi, a well-known TCM, has were used for experiments. For neuroinflammation
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been used as a tonic and sedative agent for thousands of modeling, BV2 cells were seeded into 96-well plates
years. Modern pharmacological studies have suggested at a density of 3 × 10 cells/mL, pretreated with SCF
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that Wuweizi possesses a range of biological activities, or SSF (at concentrations of 0 – 40 μg/mL) for 2 h, and
such as neuroprotective, anti-inflammatory, antioxidative, subsequently stimulated with lipopolysaccharide (LPS,
and hepatoprotective properties. 9-12 Historically, Wuweizi 1 μg/mL, Sigma, Germany) for 24 h. For the oxygen and
is referred to as the ripe fruit of both Schisandra chinensis glucose deprivation/reperfusion (OGD/R) model, SCF- or
(SCF) and Schisandra sphenanthera (SSF). However, since SSF-pretreated cells were incubated in oxygen deprivation
the 2000 edition of Chinese Pharmacopoeia (ChP), SCF (94% N + 5% CO + 1% O ) and glucose-free DMEM for
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2
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and SSF have been classified as distinct crude drugs with 6 h, followed by normal incubation for an additional 6 h.
independent quality standards, despite similarities in their
described efficacies in ChP. 13 2.2. Cell viability assay
Dibenzocyclooctadiene lignans are the major bioactive Cells were assessed using the Cell Counting Kit-8 (CCK8,
components responsible for many of the pharmacological Solarbio, China) according to the manufacturer’s protocol.
activities of SCF and SSF. 14,15 Compounds, such as Cells were incubated with CCK8 solution (10% v/v)
schisandrol A-B, schisandrin A-C, and schisantherin A for 1.5 h. Absorbance was measured at 450 nm using a
are present in both SCF and SSF, although their quantities microplate reader (Spark, Tecan, Switzerland).
differ, potentially contributing to both similar and 2.3. Griess and ELISA assay for inflammatory
distinct pharmacological effects. Recent studies have cytokines
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highlighted the neuroprotective properties of SCF and its
major constituents, particularly dibenzocyclooctadiene- After treatment, cell culture supernatants were collected
type lignans, including schisandrin A, schisandrin B, and centrifuged. The levels of nitric oxide (NO) in cell
schisandrin C, schisantherin A, schisandrin, schisandrol supernatants were determined using commercial kits
B, gomisin A, and gomisin N. These compounds have (Griess, Beyotime Biotechnology, China) according to
demonstrated protective effects against neurodegenerative the manufacturer’s instructions, and absorbance was
and hypoxia-ischemia-related neural injuries, including measured at 540 nm using a microplate reader (Spark,

Volume 4 Issue 1 (2025) 91 doi: 10.36922/gtm.6879