Objective To investigate the effects of Angelica sinensis and Astragalus membranaceus extract joint intervention on cold resistance in mice, as well as its influence on endoplasmic reticulum stress (ERS) and mitophagy-related proteins in the liver. Methods Twenty-four 8-week-old male C57BL/6 mice were acclimatized for 5 days and then divided into C group, M group and Y group by body weight, with 8 mice in each group. The C group and M group received distilled water by daily gavage, while the Y group was administered 100 mg/kg Angelica sinensis extract and 800 mg/kg Astragalus membranaceus extract. After 14 days of gavage, mice in M group and Y group were exposed to 4℃ environment for 24 hours. At the end of cold exposure, rectal temperature (core body temperature) was measured. Serum and liver samples were collected. The levels of transaminases in serum and liver were measured. Histopathology observation was conducted, and ERS and mitophagy related proteins were detected in liver. Results 4℃ exposure significantly reduced the core body temperature of mice in the M group (P<0.05). Compared with the M group, core body temperature of the Y group was significantly increased (P<0.05). Liver tissues of M group exhibited mild hydropic degeneration, enlarged intercellular spaces, disordered liver lobule structure, mitochondria swollen, rough endoplasmic reticulum locally blurred, and autophagosomes reduction. Serum and liver alanine aminotransferase (AST) and alanine aminotransferase (ALT) activities were significantly increased (P<0.05). The expressions of ERS-related proteins glucose regulated protein78 (GRP78), PKR-like ER-resident kinase (PERK), eukaryotic initiation factor 2 alpha (eIF2α), p-eIF2α, activating transcription factor-4 (ATF4), p-ATF4 and C/EBP homologous protein (CHOP) in liver tissues was significantly upregulated (P<0.05). The expression of mitophagy protein ubiquitin-binding protein p62 (p62) was significantly increased (P<0.05), while autophagy-related protein 1 with BECN1 domain (Beclin1) and the microtubule-associated proteins light chain3 (LC3）I and LC3II ratio were significantly decreased (P<0.05). In the Y group, liver structure showed significant improvements, mitochondrial edema was alleviated, and autophagosomes were visible. AST and ALT activities in the serum and liver were significantly reduced, and the expression of ERS-related proteins in the liver was significantly downregulated (P<0.05). The expression of mitophagy protein p62 was significantly decreased (P<0.05), while Beclin1 and LC3II/I ratio were significantly increased (P<0.05). Conclusion The Angelica sinensis and Astragalus membranaceus extract joint intervention elevates core body temperature during acute cold exposure, possibly through regulating liver ERS and autophagy to ameliorating liver injury.
Key words
Angelica sinensis /
Astragalus membranaceus /
acute cold exposure /
endoplasmic reticulum stress /
autophagy /
mouse
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