The effect of gallic acid on memory and anxiety-like behaviors in rats with bile duct ligation-induced hepatic encephalopathy: Role of AMPK pathway

Document Type : Original Research Article


1 Department of Anatomical Sciences, Afzalipour Medical School, Kerman University of Medical Sciences, Kerman, Iran

2 Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

3 Physiology Research Center, Institute of Basic and Clinical Physiology Sciences and Department of Physiology and Pharmacology, Kerman University of Medical Sciences, Kerman, Iran

4 Medical Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. Razi Herbal Medicine Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran


Objective: Hepatic encephalopathy (HE) is a serious neurological syndrome which is caused by acute and chronic liver diseases. In this study, the effect of gallic acid (GA) as an activator of AMP-activated protein kinase (AMPK) on memory and anxiety-like behaviors in rats with HE caused by bile duct ligation (BDL) was investigated.
Materials and Methods: The rats were randomly divided into the following eight groups (n=7): sham; BDL; BDL+GA 20 mg/kg; BDL+GA 30 mg/kg; sham+dorsomorphin or compound C (CC) (as AMPK inhibitors); BDL+CC; BDL+GA 20 mg/kg+CC; and BDL+GA 30 mg/kg+CC. The rats received GA once daily by gavage for four weeks, and dorsomorphin 6.2 µg per rat was administered on a daily basis via bilateral intraventricular injection for four weeks. Behavioral tests including novel object recognition (NOR), open field and Morris water maze (MWM) were used to evaluate anxiety and memory in the rats.
Results: Examining some parameters of NOR and MWM tests showed that memory performance was significantly reduced in the BDL versus the sham group, and in the BDL+CC versus the sham+CC group (p<0.05). GA intake improved memory in the GA-receiving groups compared with the BDL and BDL+CC groups (p<0.05). Examining some parameters of open field test showed that anxiety was significantly increased in the BDL versus the sham group, and the BDL+CC versus the sham+CC group (p<0.05). GA intake reduced anxiety in GA-receiving groups compared with the BDL+BDL+CC group (p<0.05).
Conclusion: GA was effective in improving cognitive and anxiety-like behaviors through activating AMPK.


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