Hepatoprotective potential of Vitis gracilis


J. Pharm. Pharmacogn. Res., vol. 12, no. 6, pp. 1178-1186, Nov-Dec 2024. DOI: https://doi.org/10.56499/jppres24.1983_12.6.1178 Original Article Assessing the hepatoprotective efficacy of Vitis gracilis Wall. against doxorubicin-induced hepatic injury in rats [Evaluación de la eficacia hepatoprotectora de Vitis gracilis Wall. contra la lesión hepática inducida por doxorrubicina en ratas] Yurnadi Hanafi Midoen1, Syafruddin Ilyas2*, Putra Santoso3 … Continue reading Hepatoprotective potential of Vitis gracilis

J. Pharm. Pharmacogn. Res., vol. 12, no. 6, pp. 1178-1186, Nov-Dec 2024.

DOI: https://doi.org/10.56499/jppres24.1983_12.6.1178

Original Article

Assessing the hepatoprotective efficacy of Vitis gracilis Wall. against doxorubicin-induced hepatic injury in rats

[Evaluación de la eficacia hepatoprotectora de Vitis gracilis Wall. contra la lesión hepática inducida por doxorrubicina en ratas]

Yurnadi Hanafi Midoen1, Syafruddin Ilyas2*, Putra Santoso3

1Department of Medical Biology, Faculty of Medine, Universitas Indonesia, Jakarta, Indonesia.

2Study Program of Biology, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Medan, Indonesia.

3Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Andalas, Padang, Indonesia.

*E-mail: syafruddin6@usu.ac.id


Context: Doxorubicin is an anticancer drug that can adversely affect the liver. Therefore, seeking medical attention to manage pain and minimize side effects is crucial.

Aims: To evaluate the hepatoprotective potential of Vitis gracilis Wall. nanoherbs against doxorubicin-induced hepatotoxicity.

Methods: The study included five treatment groups: T0 (negative control), T+ (positive control with doxorubicin alone), TC (doxorubicin + vitamin C at 0.2 mg/kg body weight/day), T125 (doxorubicin + V. gracilis at 125 mg/kg body weight/day), and T150 (doxorubicin + V. gracilis at 150 mg/kg body weight/day). Doxorubicin, administered intraperitoneally at 0.0019 mg/kg body weight once a week for three weeks, induced hepatotoxicity in the T+ group.

Results: Serum transaminases were significantly reduced in the T125 and T150 groups, indicative of the hepatoprotective effects of V. gracilis. Immunohistochemical analysis demonstrated the modulation of key markers, with decreased levels of pro-inflammatory tumor necrosis factor-α and increased levels of anti-inflammatory interleukin 10 in the T125 and T150 groups. The activities of oxidative stress markers, including superoxide dismutase and caspase 3, were favorably influenced by V. gracilis nanoherb treatment.

Conclusions: These findings suggest that V. gracilis nanoherbs may effectively attenuate doxorubicin-induced hepatotoxicity, evidenced by biochemical and immunohistochemical changes. This study provides a foundation for further exploration of V. gracilis nanoherbs as a potential adjunctive therapy in preventing chemotherapy-associated liver damage.

Keywords: CASP3; IL-10; serum transaminases; SOD; TNF-α.

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Contexto: La doxorrubicina es un fármaco anticancerígeno que puede afectar negativamente al hígado. Por lo tanto, es fundamental buscar atención médica para controlar el dolor y minimizar los efectos secundarios.

Objetivos: Evaluar el potencial hepatoprotector de Vitis gracilis Wall. nanohierbas contra la hepatotoxicidad inducida por doxorrubicina.

Métodos: El estudio incluyó cinco grupos de tratamiento: T0 (control negativo), T+ (control positivo con doxorrubicina sola), TC (doxorrubicina + vitamina C a 0,2 mg/kg de peso corporal/día), T125 (doxorrubicina + V. gracilis a 125 mg/kg de peso corporal/día) y T150 (doxorrubicina + V. gracilis a 150 mg/kg de peso corporal/día). La doxorrubicina, administrada por vía intraperitoneal a 0,0019 mg/kg de peso corporal una vez por semana durante tres semanas, indujo hepatotoxicidad en el grupo T+.

Resultados: Las transaminasas séricas se redujeron significativamente en los grupos T125 y T150, lo que indica los efectos hepatoprotectores de V. gracilis. El análisis inmunohistoquímico demostró la modulación de marcadores clave, con niveles reducidos de factor de necrosis tumoral α proinflamatorio y niveles elevados de interleucina 10 antiinflamatoria en los grupos T125 y T150. Las actividades de los marcadores de estrés oxidativo, incluidas la superóxido dismutasa y la caspasa 3, se vieron influenciadas favorablemente por el tratamiento con nanoherbas de V. gracilis.

Conclusiones: Estos hallazgos sugieren que las nanohierbas de V. gracilis pueden atenuar eficazmente la hepatotoxicidad inducida por doxorrubicina, evidenciada por cambios bioquímicos e inmunohistoquímicos. Este estudio proporciona una base para una mayor exploración de las nanohierbas de V. gracilis como posible terapia complementaria para prevenir el daño hepático asociado a la quimioterapia.

Palabras Clave: CASP3; IL-10; SOD; TNF-α; transaminasas séricas.

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Citation Format: Midoen YH, Ilyas S, Santoso P (2024) Assessing the hepatoprotective efficacy of Vitis gracilis Wall. against doxorubicin-induced hepatic injury in rats. J Pharm Pharmacogn Res 12(6): 1178–1186. https://doi.org/10.56499/jppres24.1983_12.6.1178

Ajami M, Seyfi M, Abdollah Pouri Hosseini F, Naseri P, Velayati A, Mahmoudnia F, Zahedirad M, Hajifaraji M (2020) Effects of stevia on glycemic and lipid profile of type 2 diabetic patients: A randomized controlled trial. Avicenna J Phytomed 10(2): 118–127. http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7103435/

AlAsmari AF, Alharbi M, Alqahtani F, Alasmari F, Alswayyed M, Alzarea SI, Al-Alallah IA, Alghamdi A, Hakami HM, Alyousef MK, Sari Y, Ali N (2021) Diosmin alleviates doxorubicin-induced liver injury via modulation of oxidative stress-mediated hepatic inflammation and apoptosis via NfkB and MAPK pathway: A preclinical study. Antioxidants 10(12): 1998. https://doi.org/10.3390/antiox10121998

Allameh A, Niayesh-Mehr R, Aliarab A, Sebastiani G, Pantopoulos K (2023) Oxidative stress in liver pathophysiology and disease. Antioxidants 12(9): 1653. https://doi.org/10.3390/antiox12091653

Allison R, Guraka A, Shawa IT, Tripathi G, Moritz W, Kermanizadeh A (2023) Drug induced liver injury–a 2023 update. J Toxicol Environ Health B Crit Rev 26(8): 442–467. https://doi.org/10.1080/10937404.2023.2261848

Alshanwani AR, Hagar H, Shaheen S, Alhusaini AM, Arafah MM, Faddah LM, Alharbi FM, Sharma AK, Fayed A, Badr AM (2022) A promising antifibrotic drug, pyridoxamine attenuates thioacetamide-induced liver fibrosis by combating oxidative stress, advanced glycation end products, and balancing matrix metalloproteinases. Eur J Pharmacol 923: 174910. https://doi.org/10.1016/j.ejphar.2022.174910

Arman M, Chowdhury KAA, Bari MS, Khan MF, Huq MMA, Haque MA, Capasso R (2022) Hepatoprotective potential of selected medicinally important herbs: evidence from ethnomedicinal, toxicological and pharmacological evaluations. Phytochem Rev 21(6): 1863–1886. https://doi.org/10.1007/s11101-022-09812-5

Ballotin VR, Bigarella LG, Brandão ABM, Balbinot RA, Balbinot SS, Soldera J (2021) Herb-induced liver injury: Systematic review and meta-analysis. World J Clin Cases 9(20): 5490–5513. https://doi.org/10.12998/wjcc.v9.i20.5490

Chang CL, Lin Y, Bartolome AP, Chen YC, Chiu SC, Yang WC (2013) Herbal therapies for type 2 diabetes mellitus: chemistry, biology, and potential application of selected plants and compounds. Evid Based Complement Alternat Med 2013:378657. https://doi.org/10.1155/2013/378657

Chen Y, Huang Y, Huang R, Chen Z, Wang X, Chen F, Huang Y (2024) Interleukin-10 gene intervention ameliorates liver fibrosis by enhancing the immune function of natural killer cells in liver tissue. Int Immunopharmacol 127: 111341. https://doi.org/10.1016/j.intimp.2023.111341

El-Gindy YM, Abu Hafsa SH, El-Deeb NM (2023) The expression of liver TNF-α gene, liver and small intestine histology of thermal stressed growing rabbits affected by allicin and lycopene. J Therm Biol 113: 103521. https://doi.org/10.1016/j.jtherbio.2023.103521

Erekat NS (2017) Cerebellar Purkinje cells die by apoptosis in the shaker mutant rat. Brain Res 1657: 323–332. https://doi.org/10.1016/j.brainres.2016.12.025

Erekat NS (2022) Programmed cell death in cerebellar Purkinje neurons. J Integr Neurosci 21(1): 30. https://doi.org/10.31083/j.jin2101030

Fathy AH, Naji RM, Bashandy MA (2023) Antioxidant and hepatoprotective effects of fig fruit extract with olive oil and date-palm fruit extract on hepatic toxicity of oral subchronic exposure to some nanoparticles in Wistar rats. J Food Qual 2023: 7584688. https://doi.org/10.1155/2023/7584688

Gajendiran P, Vega LI, Itoh K, Sesaki H, Vakili MR, Lavasanifar A, Hong K, Mezey E, Ganapathy-Kanniappan S (2018) Elevated mitochondrial activity distinguishes fibrogenic hepatic stellate cells and sensitizes for selective inhibition by mitotropic doxorubicin. J Cell Mol Med 22(4): 2210–2219. https://doi.org/10.1111/jcmm.13501

Hamaidia K, Soltani N (2019) Compensation of kinoprene effect on reproduction of Culex pipiens by methoxyfenozide, an ecdysone agonist. J Entomol Res 43(2): 125–130. https://doi.org/10.5958/0974-4576.2019.00024.0

Hammer M, Storey S, Hershey DS, Brady VJ, Davis E, Mandolfo N, Bryant AL, Olausson J (2019) Hyperglycemia and cancer: A state-of-the-science review. Oncol Nurs Forum 46(4), 459–472. https://doi.org/10.1188/19.ONF.459-472

Ilyas S (2014) Effect of methanolic Momordica charantia seed extract and depot medroxyprogesterone acetate (DMPA) to quantity and quality of rat sperm. Int J PharmTech Res 6(6): 1817–1823.

Ilyas S, Hutahaean S, Elimasni, Panjaitan SRN (2019a) Effect of turmeric rhizome extract (Curcuma longa L.) on kidney histology of preeclampsia rats (Rattus norvegicus L.). IOP Conf Ser: Earth Environ Sci 305: 012078. https://doi.org/10.1088/1755-1315/305/1/012078

Ilyas S, Santoso P, Midoen YH, Situmorang PC (2023) Improvement of spermatozoa concentration due to maximal exercise with Vitis gracilis Wall. J Pharm Pharmacogn Res 11(5): 874–886. https://doi.org/10.56499/jppres23.1685_11.5.874

Ilyas S, Tanjung RS, Hutahaean S, Tanjung M, Elimasni, Jamilah I, Murdela F (2019b) Antioxidant activity of haramounting leaf ethanol extract (Rhodomytrus tomentosa) in preventing heart damage of mice (Mus musculus L.) after exposure to electronic cigarette. IOP Conf Ser: Earth Environ Sci 305: 012080. https://doi.org/10.1088/1755-1315/305/1/012080

Irianti E, Ilyas S, Hutahaean S, Rosidah, Situmorang PC (2020) Placental histological on preeclamptic rats (Rattus norvegicus) after administration of nanoherbal haramonting (Rhodomyrtus tomentosa). Res J Pharm Technol 13(8): 3879–3882. https://doi.org/10.5958/0974-360X.2020.00686.1

Iruoghene G, Ngukuran A, Ogheneoruese F, Akpoghelie O, Johnson J, Avuokerie H, Ugbune U, Okeoghene G, Lucky O, Evi E, Oghroro A, Elizabeth A, Ahamefula K (2024) The ameliorative effects of Vernonia amygdalina extract on superoxide dismutase and glutathione s-transferase on alloxan induced diabetes on male Wistar rats. Food Chem Adv 4: 100620. https://doi.org/10.1016/j.focha.2024.100620

Januszewski AS, Blake R, Zhang M, Ma B, Anand S, Pinkert CA, Kelly DJ, Jenkins AJ, Trounce IA (2024) Increased diabetes complications in a mouse model of oxidative stress due to ‘mismatched’ mitochondrial DNA. Antioxidants (Basel) 13(2): 187. https://doi.org/10.3390/antiox13020187

Johra FT, Hossain S, Jain P, Bristy AT, Emran T, Ahmed R, Sharker SM, Bepari AK, Reza HM (2023) Amelioration of CCl4-induced oxidative stress and hepatotoxicity by Ganoderma lucidum in Long Evans rats. Sci Rep 13(1): 9909. https://doi.org/10.1038/s41598-023-35228-y

Khairani EY, Sumarmin R (2018) Effect of mangosteen fruit peel extract (Garcinia mangostana L.) on the histology of sucrose-induced pancreas of mice (Mus musculus L. Swiss Webster). [Indonesian]. EKSAKTA 19(1): 100-112. https://doi.org/10.24036/eksakta/vol19-iss01/123

Kong CY, Guo Z, Song P, Zhang X, Yuan YP, Teng T, Yan L, Tang QZ (2022) Underlying the mechanisms of doxorubicin-induced acute cardiotoxicity: Oxidative stress and cell death. Int J Biol Sci 18(2): 760–770. https://doi.org/10.7150/ijbs.65258

Kustarini I, Dewi SS, Pawitra IM (2012) Ethanol extract of Morinda citrifolia L (mengkudu), blood glucose, neutrophyl count, and glomerulus fibronectin in diabetes mellitus rat. Media Medika 46(5): 178–183.

Li Y, Zhou F, Liu F, Wang M, Xing W (2020) Experimental study on evaluation of blood supply level and embolization ratio of liver cancer based on I-Flow software. Technol Cancer Res Treat 19: 1533033820970665. https://doi.org/10.1177/1533033820970665

Linders AN, Dias IB, López Fernández T, Tocchetti CG, Bomer N, Van der Meer P (2024) A review of the pathophysiological mechanisms of doxorubicin-induced cardiotoxicity and aging. NPJ Aging 10: 9. https://doi.org/10.1038/s41514-024-00135-7

Midoen YH, Ilyas S, Santoso P, Situmorang PC (2023) Effect of maximal physical exercise on apoptosis via cytochrome c in hippocampus cells after administration of Vitis gracilis Wall. J Pharm Pharmacogn Res 11(2): 297–307. https://doi.org/10.56499/JPPRES22.1563_11.2.297

Mohammad FS, Das U, Samanta SK, Irfan Z, Gopinath SC, Mostafa MAH, Al-Haidari RA, Abdellatif AAH, Shehata AM, Gouda MM (2024) Evaluation of Sechium edule fruit attenuation impact on the cardiomyopathy of the STZ-induced diabetic rats. Heliyon 10(9): e30440. https://doi.org/10.1016/j.heliyon.2024.e30440

Nagata K, Nishiyama C (2021) IL-10 in mast cell-mediated immune responses: Anti-inflammatory and proinflammatory roles. Int J Mol Sci 22(9): 4972. https://doi.org/10.3390/ijms22094972

Raghavan G, Bapna A, Mehta A, Shah A, Vyas T (2023) Effect of sugar replacement with stevia-based tabletop sweetener on weight and cardiometabolic health among Indian adults. Nutrients 15(7): 1744. https://doi.org/10.3390/nu15071744

Sabri E, Ilyas S, Prasetiawan E (2018) The effect of n-hexane extract of andaliman (Zanthoxylum acanthopodium DC.) fruit in the liver tissues of mice during post implantation of pregnancy. J Phys: Conf Ser 1116(5): 052056. https://doi.org/10.1088/1742-6596/1116/5/052056

Santoso P, Ilyas S, Midoen YH, Situmorang PC (2023) Effect of Vitis gracilis Wall. administration on maximal swimming exercise apoptosis via cytochrome c in rat lung cells. J Pharm Pharmacogn Res 11(3): 381–390. https://doi.org/10.56499/jppres23.1603_11.3.381

Satria D, Silalahi J, Haro G, Ilyas S, Hasibuan PAZ (2019) Chemical analysis and cytotoxic activity of N-hexane fraction of Zanthoxylum acanthopodium DC. fruits. Rasayan J Chem 12(2): 803-808. https://doi.org/10.31788/RJC.2019.1225180

Senavirathna T, Shafaei A, Lareu R, Balmer L (2024) Unlocking the therapeutic potential of ellagic acid for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Antioxidants 13(4): 485. https://doi.org/10.3390/antiox13040485

Shati AA, Eid RA, El-Kott AF, Alqahtani YA, Shatoor AS, Ahmed Zaki MS (2024) Curcumin attenuates doxorubicin-induced cardiotoxicity via suppressing oxidative stress, preventing inflammation and apoptosis: Ultrastructural and computational approaches. Heliyon 10(5): e27164. https://doi.org/10.1016/j.heliyon.2024.e27164

Shen B, Zhang H, Zhu Z, Ling Z, Zeng F, Wang Y, Wang J (2023) Baicalin relieves LPS-induced lung inflammation via the NF-κB and MAPK pathways. Molecules 28(4): 1873. https://doi.org/10.3390/molecules28041873

Sheweita SA, Alian DME, Haroun M, Nounou MI, Patel A, El-Khordagui L (2023) Chitosan nanoparticles alleviated the adverse effects of sildenafil on the oxidative stress markers and antioxidant enzyme activities in rats. Oxid Med Cell Longev 2023(1): 9944985. https://doi.org/10.1155/2023/9944985

Silitonga M, Ilyas S, Hutahaean S, Sipahutar H (2014) Levels of apigenin and immunostimulatory activity of leaf extracts of bangunbangun (Plectranthus amboinicus Lour). Int J Biol 7(1): 46–53. https://doi.org/10.5539/ijb.v7n1p46

Situmorang PC, Ilyas S (2018) Study of preeclampsia in placenta, kidney, and hepatic diseases. Asian J Pharm Clin Res 11(11): 21–28. https://doi.org/10.22159/ajpcr.2018.v11i11.27540

Situmorang PC, Ilyas S, Hutahaean S, Rosidah R (2019) Effect of nanoherbal andaliman (Zanthoxylum acanthopodium) and extra virgin olive oil combination on preeclamptic rats liver histology. Open Access Maced J Med Sci 7(14): 2226–2231. https://doi.org/10.3889/oamjms.2019.651

Stamataki NS, Scott C, Elliott R, McKie S, Bosscher D, McLaughlin JT (2020) Stevia beverage consumption prior to lunch reduces appetite and total energy intake without affecting glycemia or attentional bias to food cues: A double-blind, randomized controlled trial in healthy adults. J Nutr 150(5): 1126–1134. https://doi.org/10.1093/jn/nxaa038

Stoessel MB, Majewska AK (2021) Little cells of the little brain: microglia in cerebellar development and function. Trends Neurosci 44(7): 564–578. https://doi.org/10.1016/j.tins.2021.04.001

Taepongsorat L, Phadungkit M (2018) Effects of Asparagus racemosus root extracts on serum lipid profiles, lipid peroxidation and superoxide dismutase in ovariectomized rat. Pharmacogn J 10(5): 1036–1041. https://doi.org/10.5530/pj.2018.5.175

Wasnis NZ, Ilyas S, Hutahaean S, Silaban R, Situmorang PC (2022) Effect of Vitis gracilis Wall (gagatan harimau) in the recovery of gastrocnemius muscle cells and cytochrome c expression of Mus musculus. J Pharm Pharmacogn Res 10(2): 303–309. https://doi.org/10.56499/jppres21.1208_10.2.303

Xiaobo W, Yating Z, Ya H, Hong J, Yi Z, Sanyin Z, Xianli M (2023) Preclinical anti-apoptotic properties of salidroside for hypoxic-ischemic cerebral damage: A systematic review and meta-analysis. Digit Chin Med 6(2): 121–135. https://doi.org/10.1016/j.dcmed.2023.07.003

Yashkin AP, Gorbunova GA, Tupler L, Yashin AI, Doraiswamy M, Akushevich (2023) Differences in risk of Alzheimer’s disease following later-life traumatic brain injury in veteran and civilian populations. J Head Trauma Rehabil 38(6): E384–E393. https://doi.org/10.1097/HTR.0000000000000865

Yulizal OK, Lelo A, Ilyas S, Kusumawati RL (2020) Correlation of macrophage migration inhibitory factor (MIF) expression and asymmetric dimethylarginine (ADMA) levels in Helicobacter pylori Infection. In: Proceedings of the 2020 12th International Conference on Bioinformatics and Biomedical Technology (ICBBT '20). New York, NY, USA: Association for Computing Machinery, pp. 134–138. https://doi.org/10.1145/3405758.3405779

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