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Outline
Plant-derived nanovesicles are nano-sized extracellular vesicles that encapsulate nucleic acids, proteins, and lipids, and exert antioxidant, anti-inflammatory, antitumor, and tissue-regenerative effects, showing great potential for disease intervention. Schisandra chinensis (Turcz.) Baill., a traditional medicinal plant, has been extensively studied by our group and others for its hepatoprotective constituents and mechanisms of action. Excessive acetaminophen (APAP) intake is the leading cause of drug-induced liver injury in clinical practice, yet effective and low-toxicity preventive or therapeutic strategies are still lacking. To investigate the protective effect and mechanism of Schisandra chinensis-derived nanovesicles (SSDNs) against APAP-induced acute liver injury in mice, SSDNs were first isolated from Schisandra chinensis by gradient ultrahigh-speed centrifugation. Transmission electron microscopy and nanoparticle tracking analysis revealed an exosome-like bilayer membrane, uniform morphology, and a mean diameter of 205.4 nm. In vitro CCK-8 assays showed that SSDNs exhibited no cytotoxicity. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis identified schisandrol A as the major lignan component of SSDNs. Furthermore, we evaluated the protective effect of SSDNs on APAP-induced acute liver injury in mice. All experimental protocols were approved by the Animal Ethics Committee of Southern Medical University (approval No. SMUL202408016). C57BL/6 mice were pretreated with SSDNs via tail vein injection for 4 days and then given a single intraperitoneal injection of APAP (400 mg·kg-1). Pretreatment with SSDNs significantly lowered serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, reduced hepatic necrosis, and restored lobular architecture. Concurrently, SSDNs elevated the hepatic glutathione (GSH) level, decreased protein expression of APAP-metabolizing enzymes cytochrome P450 (CYP) 2E1 and CYP3A11, and upregulated proliferating cell nuclear antigen (PCNA) and cell-cycle proteins [cyclin-dependent kinase 4 (CDK4), cyclin A1 (CCNA1), cyclin D1 (CCND1), and cyclin E1 (CCNE1)]. In conclusion, SSDNs mitigate APAP-induced acute liver injury in mice by preserving hepatic GSH, suppressing CYP450 enzymes involved in APAP metabolic activation, and promoting hepatocyte proliferation and repair. These findings offer a novel strategy for the modern application of Schisandra chinensis and the clinical prevention of APAP-induced hepatotoxicity.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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