Zingerone ameliorates non‐alcoholic fatty liver disease in rats by activating AMPK

Abstract

This study was conducted to test the protective potential of Zingerone against a highfat diet (HFD)-mediated non-alcoholic fatty liver disease (NAFLD) development in rats and examined in this protection is mediated modulating AMP-activated protein kinase (AMPK). Animals were segregated based on their diet and treatment into four groups (n = 6 each): (a) fed standard diet (STD), (b) treated with Zingerone (100 mg/kg), (c) fed HFD, (d) HFD + Zingerone (100 mg/kg), and (e) HFD + Zingerone (100 mg/kg) + compound c (CC) (an AMPK inhibitor) (0.2 mg/kg). The treatment with Zingerone attenuated the gain in final body weights, preserved liver structure, and downregulated the transcription of Bax and cleaved caspase-3. In the HFD and STD-fed rats, Zingerone reduced levels of fasting glucose and insulin and circulatory levels of cholesterol (CHOL) and triglycerides (TGs). Concomitantly, Zingerone enhanced glutathione (GSH) and superoxide dismutase (SOD) levels, depleted levels of malondialdehyde (MDA), and enhanced the nuclear levels of the nuclear factor erythroid 2-related factor 2 (Nrf2).In addition, it lowered the levels of inflammatory cytokines and the nuclear levels of the nuclear factor kappa beta p65 (NF-κB p65). All these biochemical changes were associated with an increment in the phosphorylation of AMPK (p-AMPK) (activation) and reduced mRNA levels of SREBP1 and SREBP2. All observed effects afforded by Zingerone were abolished by CC. In conclusion, Zingerone prevents hepatic oxidative stress, inflammation, and apoptosis by activating AMPK.

Neonatal Orally Administered Zingerone Attenuates Alcohol-Induced Fatty Liver Disease in Experimental Rat Models

“…In vivo zingerone activates PPAR-α [ 57 ]. It is therefore possible that it exerted its antisteatotic effects by preventing the downregulation of PPAR-α Additionally, previous research had found that zingerone can suppress the expression of SREBP1c [ 33 ] to protect against fatty liver formation and lipid accumulation therefore our findings are in tandem with other research outcomes.…”

“…Several pharmacological agents have proven effective as potential prophylaxes in managing adverse effects induced by exposure to toxic substances during periods of developmental plasticity [ 32 , 33 , 34 ]. Zingerone has been reported to possess antisteatotic properties that can protect against the development of fatty liver via the activation of AMP-activated protein kinase (AMPK) [ 33 , 35 ]. Furthermore, oral supplementation of 40 mg/kg body wt of zingerone via intragastric intubation to alcohol-fed Wistar rats protected against hepatoxicity [ 36 ].…”

Unveiling the Hub Genes Associated with Manganese-Induced Hepatotoxicity

“…Mohammed (2022) found that the activation of AMPK signaling pathway reduced hepatic oxidative stress, in ammation, and apoptosis in NAFLD. The phosphorylation of AMPK enhanced the activities of GSH and SOD, depleted MDA concentration, and enhanced NRF2 level [44]. AMPK signaling pathway exerts hepatoprotective effect against concanavalin A-induced hepatitis in mice [45].…”

Plantamajoside modulates immune dysregulation and hepatic lipid metabolism in rats with nonalcoholic fatty liver disease viaAMPK/Nrf2 elevation

“…PMS was bought from Sigma (PHL83304, St. Louis, MO, USA) with a purity of ≥95.0% (HPLC). Rats in HFD + 80 mg/kg PMS + CC group were intraperitoneally injected with 80 mg/kg PMS and intragastrically administered with the inhibitor of AMPK pathway compound C (CC, 0.2 mg/kg) (P5499, purity≥98% [HPLC], Sigma) 18 once a day for 4 weeks. At the end of experiment, rats were weighed, and then intraperitoneally injected with sodium pentobarbital (100 mg/kg) for sacrifice.…”

“…[HPLC], Sigma) 18 once a day for 4 weeks. At the end of experiment, rats were weighed, and then intraperitoneally injected with sodium pentobarbital (100 mg/kg) for sacrifice.…”