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Edible Fungus Compound Cordycepin Protects Against Acetaminophen-Induced Liver Injury
Chunjin Fu1, Shuyu Li1, Shengnan Shen1
1State Key Laboratory for Quality Assurance and Sustainable Use of Dao-di Herbs, China Academy of Chinese Medical Sciences, Beijing, China.
Cordyceps militaris (COR) pretreatment protects against acetaminophen (APAP)-induced liver injury by reducing inflammation, oxidative stress, and apoptosis. COR modulates ER proteostasis and signaling pathways, showing promise as a hepatoprotective agent.
Area of Science:
- Pharmacology
- Toxicology
- Natural Products Chemistry
Background:
- Medicinal-edible natural products like Cordyceps militaris (C. militaris) offer health benefits.
- Cordycepin (COR), found in C. militaris, has anti-inflammatory and antioxidant properties.
- The protective effects of COR against acetaminophen (APAP)-induced liver injury are not well understood.
Purpose of the Study:
- To evaluate the protective effects of COR pretreatment against APAP-induced acute liver injury in mice.
- To elucidate the underlying molecular mechanisms of COR's hepatoprotective action.
Main Methods:
- Male C57BL/6 mice were pretreated with COR (50, 100, or 200 mg/kg) or N-acetylcysteine (NAC) for 7 days.
- Liver injury was induced by APAP administration (400 mg/kg).
- Evaluations included serum transaminases, histopathology, inflammatory cytokines, oxidative stress markers, TUNEL staining, and RNA-seq transcriptomic analysis.
Main Results:
- COR pretreatment significantly reduced serum transaminases and alleviated liver necrosis and inflammation.
- RNA-seq analysis showed COR reversed APAP-induced changes in genes related to ER protein processing, HIF-1, and PPAR signaling.
- COR decreased pro-inflammatory cytokines, mitigated oxidative damage, and inhibited hepatocyte apoptosis.
Conclusions:
- COR pretreatment attenuates APAP-induced hepatotoxicity by modulating ER proteostasis and influencing HIF-1 and PPAR signaling.
- COR exhibits anti-inflammatory, antioxidant, and anti-apoptotic effects.
- COR is a promising candidate for mitigating APAP-induced liver damage.
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