Chlorpyrifos (CPF) is widely used in agriculture, plants, and buildings to kill pests and worms. Excessive environmental residues of CPF will result in soil and ecological contamination and toxicity to animals and humans. Baicalein (Bai), derived from the root of natural Scutellaria baicalensis, is a potent anti-inflammatory, antioxidant, and antitumor agent. The objective of this paper is to investigate the molecular mechanism by which Bai prevents CPF-induced hepatotoxic injury. Carp were kept in water containing CPF (23.2 μg/L) and/or fed diets containing Bai (0.15 g/kg). We found that Bai attenuated liver tissue damage and vacuolization caused by CPF. We confirmed that CPF causes M1/M2 polarization imbalance in macrophages and hepatocyte pyroptosis, which ultimately leads to liver injury. Further exploration of the internal mechanism shows that CPF participates in liver toxicity damage by destroying the AMPK/SIRT1/pGC-1α pathway and causing mitochondrial biogenesis and mitochondrial dynamics imbalance. Notably, Bai significantly attenuated CPF-induced inhibition of the AMPK/SIRT1/pGC-1α pathway. In summary, our results suggest that Bai alleviates CPF exposure-induced inhibition of the AMPK/SIRT1/pGC-1α pathway, thereby attenuating macrophage M1 hyperpolarization and pyroptosis by inhibiting the NF-κB pathway. These results may provide new insights into the detoxification mechanism of Bai on the same type of organophosphorus pesticides.
Man Hu,Wen Jiang,Chen Ye,Ting Hu,Qingqing Yu,Moran Meng,Lijuan Sun,Jichao Liang,Yong Chen
Schwann cells injury induced by high glucose (HG) contributes to the development of diabetic peripheral neuropathy (DPN). Honokiol has been reported to regulate glucose metabolism, however, its effect on DPN and the precise molecular mechanisms remain unclear. This study aimed to investigate the role of AMPK/SIRT1/PGC-1α axis in the protective effects of honokiol on DPN. The biochemical assay and JC-1 staining results demonstrated that honokiol reduced HG-induced oxidative stress and ferroptosis as well as mitochondrial dysfunction in Schwann cells. RT-qPCR and western blotting were utilized to investigate the mechanism of action of honokiol, and the results showed that HG-induced inhibition of AMPK/SIRT1/PGC-1α axis and changes of downstream gene expression profile were restored by honokiol. Moreover, silencing of Sirt1 by siRNA delivery markedly diminished the changes of gene expression profile induced by honokiol in HG-induced Schwann cells. More importantly, we found that administration of honokiol remarkably attenuated DPN via improving sciatic nerve conduction velocity and increasing thermal and mechanical sensitivity in streptozotocin-induced diabetic rats. Collectively, these results demonstrate that honokiol can attenuate HG-induced Schwann cells injury and peripheral nerve dysfunction, suggesting a novel potential strategy for treatment of DPN.
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