Echinacoside improves diabetic liver injury by regulating the AMPK/SIRT1 signaling pathway in db/db mice

Aims: Echinacoside (ECH) is a natural compound extracted from the stem of the Cistanche deserticola plant, has significant biological properties, including antioxidant, anti-inflammatory, neuroprotective, anti-tumor, hepatoprotective, and immunomodulatory properties. In this study, we aimed to explore the protection effects and mechanisms of ECH on diabetic liver injury in db/db mice. Main methods: Overall, 6-week-old db/db mice (n = 20) were randomly allocated to 2 groups: diabetic model group (db/db group, intragastric administration of normal saline, n = 10) and ECH-treated group (db/db + ECH group, n = 10). Additionally, the normal control group comprised 6-week-old db/m mice (db/m group, normal saline intragastric administration, n = 10). ECH was administered once a day for 10 weeks. Weight and fasting blood glucose (FBG) were measured biweekly. HE staining and Oil O staining were used to evaluate liver tissue pathological changes and lipid accumulation respectively. Immunofluorescence staining, Western blot and RT-PCR analysis were used to detect the expression of components of the AMPK/SIRT1 signaling axis. Key findings: The results showed that the administration of echinacoside for 10 weeks could significantly improve liver injury and insulin resistance in db/db mice (p < 0.01). Also, echinacoside treatment helped to reduce blood lipids and blood glucose (p < 0.01). Moreover, ECH actived AMPK/SIRT1 signaling, upregulated pemxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1 alpha), proliferator-activated receptor-alpha (PPAR alpha), carnitine palmitoyl transferase-1A (CPT1A) in db/db mice (p < 0.01). Significance: The effect of ECH may be elicited by the activation of the liver AMPK/SIRT1 pathway and its downstream factors to improve adiposity, insulin resistance, and dyslipidemia.

Automated summary

The study demonstrated that echinacoside treatment significantly improved liver injury and insulin resistance in db/db mice, reduced blood lipids and glucose levels. Additionally, ECH activated the AMPK/SIRT1 signaling pathway and upregulated key factors in lipid metabolism in the mice.