Hepatoprotective Effects of Gac (Momordica cochinchinensis) Aril Extract in Acetaminophen-Induced Liver Injury: Modulation of Oxidative Stress, Inflammation, and Glucose Metabolism
Piyanuch Lonan,1 Varitha Ariyabukalakorn,2 Bhornprom Yoysungnoen,3 Kanathip Singsai,4 Ratsada Praphasawat,5 Sarawut Sangkham,6 Nattanida Jantarach,2 Prathakphong Riyamongkhol,7 Nuntiya Somparn,8 Narongsuk Munkong5 1Traditional Chinese Medicine Program, School of Public Health, University of Phayao,...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2025-08-01
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| Series: | Journal of Experimental Pharmacology |
| Subjects: | |
| Online Access: | https://www.dovepress.com/hepatoprotective-effects-of-gac-momordica-cochinchinensis-aril-extract-peer-reviewed-fulltext-article-JEP |
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| Summary: | Piyanuch Lonan,1 Varitha Ariyabukalakorn,2 Bhornprom Yoysungnoen,3 Kanathip Singsai,4 Ratsada Praphasawat,5 Sarawut Sangkham,6 Nattanida Jantarach,2 Prathakphong Riyamongkhol,7 Nuntiya Somparn,8 Narongsuk Munkong5 1Traditional Chinese Medicine Program, School of Public Health, University of Phayao, Phayao, Thailand; 2Applied Thai Traditional Medicine Program, School of Public Health, University of Phayao, Phayao, Thailand; 3Division of Physiology, Department of Preclinical Science, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand; 4Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; 5Department of Pathology, School of Medicine, University of Phayao, Phayao, Thailand; 6Department of Environmental Health, School of Public Health, University of Phayao, Phayao, Thailand; 7Laboratory Animal Research Center Innovation and Technology Transfer Institute, University of Phayao, Phayao, Thailand; 8Division of Pharmacology, Department of Preclinical Science, Faculty of Medicine, Thammasat University, Pathum Thani, ThailandCorrespondence: Narongsuk Munkong, Department of Pathology, School of Medicine, University of Phayao, Phayao, 56000, Thailand, Tel +66 84 140 0249, Email jittmunkong@gmail.comBackground: N-acetyl-p-aminophenol (APAP) overdose remains a leading cause of acute liver failure worldwide. The aril extracts derived from Gac (Momordica cochinchinensis) (MC) fruit contain diverse phytonutrients that exhibit a range of pharma-nutritional properties, including antioxidant and anti-hepatic damage properties. Despite the therapeutic potential, the molecular mechanisms underlying its hepatoprotective action, particularly in preventing drug-induced toxicity, remain unelucidated.Purpose: This study investigated the hepatoprotective potential of MC in a mouse model of APAP-induced acute liver injury and characterized its bioactive compounds.Methods: MC was prepared using aqueous extraction. Mice were pre-treated with either 500 or 1,000 mg/kg of MC for seven consecutive days prior to intraperitoneal administration of APAP 300 mg/kg to induce hepatotoxicity. Serum and liver samples were then collected to analyze biochemical changes, histopathological changes, oxidative stress markers, and/or mRNA expression. Standard chemical tests were used to identify bioactive compounds.Results: APAP administration caused a marked rise in liver enzymes, extensive histological necrosis, suppression of hepatocyte proliferation, infiltration of neutrophils and macrophages, and significant oxidative damage (p < 0.05). Studies revealed the constitution of MC as phenolic compounds, flavonoids, proanthocyanidins, and ascorbic acid, significantly attenuated the hepatotoxicity (p < 0.05). Mechanistically, MC ameliorated hepatic mRNA expression of CYP2E1, JNK, Ddit3, Bax, Casp3, NF-κB, and MCP-1, while increasing Bcl-2, IL-10, VEGF, Nrf2, SOD2, and GCLC mRNA (p < 0.05). Furthermore, MC prevented hyperglycemia by influencing the expression of AdipoR1, GLUT-2, and PEPCK (p < 0.05).Conclusion: MC exhibits hepatoprotective effects against APAP-induced liver injury through multifaceted modulation of toxic metabolism (CYP2E1), cell death and ER stress (JNK, Ddit3, Bax, Casp3, and Bcl-2), antioxidant response (Nrf2 pathway), inflammation (NF-κB pathway and IL-10), tissue repair (VEGF), and glucose metabolism (AdipoR1, GLUT-2, and PEPCK). Keywords: acetaminophen, anti-hyperglycemia, antioxidant, immunomodulation, Momordica cochinchinensis |
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| ISSN: | 1179-1454 |