J. Pharm. Pharmacogn. Res., vol. 11, no. 6, pp. 1002-1016, Nov-Dec 2023.
DOI: https://doi.org/10.56499/jppres23.1732_11.6.1002
Original Article
Hepatoprotective study of Indonesian water kefir against CCl4-induced liver injury in rats
[Estudio hepatoprotector del kéfir de agua indonesio contra la lesión hepática inducida por CCl4 en ratas]
Widhya Aligita1,3*, Marlia Singgih2, Entris Sutrisno3, I Ketut Adnyana1*
1Department of Pharmacology & Clinical Pharmacy, School of Pharmacy, Bandung Institute of Technology, Bandung, Indonesia.
2Department of Pharmacochemistry, School of Pharmacy, Bandung Institute of Technology, Bandung, Indonesia.
3Department of Pharmacology & Clinical Pharmacy, Faculty of Pharmacy, Bhakti Kencana University, Bandung, Indonesia.
*E-mail: widhya.aligita@bku.ac.id; ketut@itb.ac.id
Abstract
Context: Water kefir is a fermented beverage that is typically made in the home by inoculating a sugar-rich solution with a microbial community (water kefir grains). Several studies on the metabolite content and hepatoprotective effects of water kefir have been published, but carbon tetrachloride (CCl4)-induced acute liver injury has not been studied.
Aims: To evaluate the efficacy of water kefir in vivo against hepatoprotective CCl4-induced acute liver injury and to in silico investigate metabolites that play an important role in hepatoprotective mechanisms.
Methods: The present study aimed to investigate the hepatoprotective activity of water kefir in an animal model caused by CCl4. Furthermore, using molecular docking, the metabolites found in water kefir were evaluated for their role in the NF-κB and Nrf2 signaling pathways.
Results: Water kefir significantly and dose-dependently alleviated acute liver injury caused by CCl4. Water kefir administration at all doses produced results comparable to the positive control (Curcuma extract). Molecular docking simulations showed that, compared to Nrf2, the 25 metabolites were more likely to interact with the NF-kB receptor. Fumaric acid is the strong metabolite that interacts with the NF-κB receptor with a free energy of binding and an inhibition constant of -6.66 kcal/mol and 13.22 µM, respectively.
Conclusions: Water kefir administration improved the condition of liver damage, characterized by a decrease in serum levels of AST, ALT, TNF-a, TGF-b, and an improvement in the liver tissue profile. In silico evaluation showed that the metabolites in water kefir were able to interact with target proteins in the NF-kB and Nrf2 pathways. It was concluded that water kefir improves the condition of the liver by reducing the level of necrosis and fibrosis.
Keywords: free radicals; liver diseases; kefir; molecular docking simulation; probiotics.
Resumen
Contexto: El kéfir de agua es una bebida fermentada que se suele elaborar en casa inoculando una solución rica en azúcar con una comunidad microbiana (granos de kéfir de agua). Se han publicado varios estudios sobre el contenido de metabolitos y los efectos hepatoprotectores del kéfir de agua, pero no se ha estudiado la lesión hepática aguda inducida por tetracloruro de carbono (CCl4).
Objetivos: Evaluar la eficacia del kéfir de agua in vivo contra la lesión hepática aguda inducida por CCl4 hepatoprotectora e investigar in silico los metabolitos que desempeñan un papel importante en los mecanismos hepatoprotectores.
Métodos: El presente estudio tuvo como objetivo investigar la actividad hepatoprotectora del kéfir de agua en un modelo animal causado por CCl4. Además, mediante docking molecular, se evaluó el papel de los metabolitos presentes en el kéfir de agua en las vías de señalización NF-κB y Nrf2.
Resultados: El kéfir de agua alivió de forma significativa y dependiente de la dosis la lesión hepática aguda causada por CCl4. La administración de kéfir de agua a todas las dosis produjo resultados comparables a los del control positivo (extracto de cúrcuma). Las simulaciones de acoplamiento molecular mostraron que, en comparación con el Nrf2, los 25 metabolitos eran más propensos a interactuar con el receptor NF-kB. El ácido fumárico es el metabolito más potente. El ácido fumárico es el metabolito fuerte que interacciona con el receptor NF-κB con una energía libre de unión y una constante de inhibición de -6,66 kcal/mol y 13,22 µM, respectivamente.
Conclusiones: La administración de kéfir de agua mejoró el estado de daño hepático, caracterizado por una disminución de los niveles séricos de AST, ALT, TNF-α, TGF-b, y una mejora del perfil tisular hepático. La evaluación in silico mostró que los metabolitos del kéfir de agua eran capaces de interactuar con proteínas diana en las vías NF-kB y Nrf2. Se concluyó que el kéfir de agua mejora el estado del hígado al reducir el nivel de necrosis y fibrosis.
Palabras Clave: enfermedades hepáticas; kéfir; probióticos; radicales libres; simulación de acoplamiento molecular.
Citation Format: Aligita W, Singgih M, Sutrisno E, Adnyana IK (2023) Hepatoprotective study of Indonesian water kefir against CCl4-induced liver injury in rats. J Pharm Pharmacogn Res 11(6): 1002–1016. https://doi.org/10.56499/jppres23.1732_11.6.1002
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