Alleviation of nonalcoholic steatohepatitis induced by tetracycline in rats by Coffee Arabica extract through autophagy signals (mTOR/LC3-B)

Abstract

The autophagy mechanism is a key point for liver protection against nonalcoholic steatohepatitis (NASH). By specifically selecting Coffea arabica, this study leverages its high concentration of chlorogenic acid to modulate autophagy, a critical cellular recycling process that is typically suppressed during the development of NASH-related liver damage. We investigated the impact of Coffea Arabica methanolic extract (CAME) on autophagy-related markers (mTOR and LC3-B) mediated abrogation of tetracycline (TET) induced NASH in rats. Sixty male albino rats weighing 150 ± 10 g were equally divided into six groups: group 1 (control) received a chow diet; group 2 (NASH) received TET orally (1 g/kg bw) for 8 days; group 3 (CAME) received Coffea Arabica methanolic extract (CAME) orally (100 mg/kg bw) for 28 days; group 4 (treatment) received TET then CAME treatment for 28 days; group 5 (preventive) received CAME (100 mg/kg) for 28 days then TET orally (1 g/kg) for 8 days; and group 6 (protective) received both TET and CAME orally for 8 days. ELISA technique was used to measure mTOR and LC3-B content in liver tissue homogenate. Moreover, transmission electron microscope analysis carried out to detect pathological alterations in liver tissue. Also, molecular docking analysis was done. Coffea Arabica methanolic extract analysis by GC/MS revealed that CAME contained the highest percentage of chlorogenic acid (12.7963%). The biochemical data obtained pointed out that the mTOR level was significantly increased (~71.62%) while LC3-B decreased (~28.08%) in the NASH group compared with control. Administration of CAME abrogated these abnormalities. Liver examination by electron microscope indicated improvement abnormalities caused by TET in treatment with CAME. Docking study showed that chlorogenic acid has binding energy − 7.554 favorable to mTOR than ATP-γS. We concluded that CAME stimulated a protective mechanism against NASH via LC3B and mTOR modulation which should attract further research to confirm our results and fully understand its mechanism of induction.