Effect of Vernonia Cinerea Water Extract on the Protection of Liver Tissue in Chronic Nicotine-Treated Rats

Chamaiporn Promputta; Vipavee Anupunpisit; Gun  Anantasomboon; Ronnarong Palasoon; Anucha Wimoonchart; Wauranittha Timklay

doi:10.59796/jcst.V14N3.2024.67

Authors

Chamaiporn Promputta Anatomy unit, Department of Biomedical Science, Faculty of Science, Rangsit University, Pathum Thani 12000, Thailand
Vipavee Anupunpisit Kasem Bundit University, Bangkok 10250, Thailand
Gun Anantasomboon Anatomy unit, Department of Biomedical Science, Faculty of Science, Rangsit University, Pathum Thani 12000, Thailand
Ronnarong Palasoon Anatomy unit, Department of Biomedical Science, Faculty of Science, Rangsit University, Pathum Thani 12000, Thailand
Anucha Wimoonchart Anatomy unit, Department of Biomedical Science, Faculty of Science, Rangsit University, Pathum Thani 12000, Thailand
Wauranittha Timklay Anatomy unit, Department of Biomedical Science, Faculty of Science, Rangsit University, Pathum Thani 12000, Thailand

DOI:

https://doi.org/10.59796/jcst.V14N3.2024.67

Keywords:

Vernonia cinerea Less., Chronic nicotine, Kupffer cell, Liver inflammation, Liver fibrosis

Abstract

Nicotine, a highly toxic alkaloid found in tobacco, is known for its addictive properties and systemic side effects, including carcinogenic potential and multi-organ damage. Recent evidence indicates that nicotine can significantly impair liver function and regeneration by promoting fibrogenesis and oxidative stress. This study aimed to investigate the protective effects of Vernonia cinerea (VC) against nicotine-induced liver damage in Wistar rats, focusing on inflammation and pro-fibrosis markers. Thirty male Wistar rats were divided into three groups: a control group, a nicotine group (1 mg/kg/day), and a nicotine plus VC group (1 mg/kg/day nicotine and 100 mg/kg/day VC). Liver tissues were examined using Hematoxylin and Eosin staining, and Masson's trichrome staining to evaluate histological changes. Kupffer cell counts were determined using a Panoramic digital slide scanner. Statistical analyses were conducted to compare the groups. Nicotine exposure led to significant liver damage, characterized by increased inflammation, collagen deposition, and disruption of liver architecture. VC supplementation ameliorated these effects, reducing inflammation and fibrosis markers. Kupffer cell counts were lower in the nicotine plus VC group compared to the nicotine group alone. Conclusion: VC demonstrates a protective role in mitigating nicotine-induced liver damage, highlighting its potential as a therapeutic agent for preventing liver fibrosis and maintaining liver health in nicotine-exposed individuals.

References

Al-Khayri, J. M., Sahana, G. R., Nagella, P., Joseph, B. V., Alessa, F. M., & Al-Mssallem, M. Q. (2022). Flavonoids as Potential Anti-Inflammatory Molecules: A Review. Molecules, 27(9), Article 2901. https://doi.org/10.3390/molecules27092901

Amuthan, A., Devi, V., Shreedhara, C. S., Rao, V., Jasphin, S., & Kumar, N. (2021). Vernonia cinerea regenerates tubular epithelial cells in cisplatin induced nephrotoxicity in cancer bearing mice without affecting antitumor activity. Journal of Traditional and Complementary Medicine, 11(3), 279–286. https://doi.org/10.1016/j.jtcme.2020.08.004

Bataller, R., & Brenner, D. A. (2005). Liver fibrosis. Journal of Clinical Investigation, 115(2), 209–218. https://doi.org/10.1172/JCI200524282

Benowitz, N. L. (2010). Nicotine addiction. The New England Journal of Medicine, 362(24), 2295–2303. https://doi.org/10.1056/NEJMra0809890

Bissel, D. M., Gores, G. J., Laskin, D. L., & Hoorhagle, J. H. (2001). Drug-induced liver injury: mechanisms and test systems. Hepatology, 33(4), 1009–1013. https://doi.org/10.1053/jhep.2001.23505

Borém, L. M., Neto, J. F., Brandi, I. V., Lelis, D. F., & Santos, S. H. (2018). The role of the angiotensin II type I receptor blocker telmisartan in the treatment of non-alcoholic fatty liver disease: a brief review. Hypertension Research, 41(6), 394-405. https://doi.org/10.1038/s41440-018-0040-6

Demiroren, K., Basunlu, M. T., Erten, R., & Cokluk, E. (2018). A comparison of the effects of thymoquinone, silymarin and N-acetylcysteine in an experimental hepatotoxicity. Biomedicine & Pharmacotherapy, 106, 1705-1712. https://doi.org/10.1016/j.biopha.2018.07.125

Emadi, S. A., Rahbardar, M. G., Mehri, S., & Hosseinzadeh, H. (2022). A review of therapeutic potentials of milk thistle (Silybum marianum L.) and its main constituent, silymarin, on cancer, and their related patents. Iranian Journal of Basic Medical Sciences, 25(10), 1166–1176. https://doi.org/10.22038/IJBMS.2022.63200.13961

Hukkanen, J., Jacob, P., & Benowitz, N. L. (2005). Metabolism and disposition kinetics of nicotine. Pharmacological Reviews, 57(1), 79-115. https://doi.org/10.1124/pr.57.1.3

Hwang, J. H., Heo, W., Park, J. I., Kim, K. M., Oh, H. T., Yoo, G. D., ... & Hong, J. H. (2023). Endothelial TAZ inhibits capillarization of liver sinusoidal endothelium and damage-induced liver fibrosis via nitric oxide production. Theranostics, 13(12), 4182–4196. https://doi.org/10.7150/thno.83714

Jensen, K., Afroze, S., Ueno, Y., Rahal, K., Frenzel, A., Sterling, M., ... & Glaser, S. S. (2013). Chronic nicotine exposure stimulates biliary growth and fibrosis in normal rats. Digestive and Liver Disease, 45(9), 754–761. https://doi.org/10.1016/j.dld.2013.02.023

Jongrungruangchok, S., Pradubyat, N., Songsak, T., Jarintanun, F., Wall, M., Chang, L. C., & Wongwiwatthananukit, S. (2019). Cytotoxicity and induction of the apoptotic activity of hirsutinolide series/sesquiterpene lactones from Vernonia cinerea on human colorectal cancer cells (COLO 205). Journal of Current Science and Technoogy, 9(1), 41-47. https://ph04.tci-thaijo.org/index.php/JCST/article/view/456

Kierszenbaum, A. L., & Tres, L. L. (2019). Histology and Cell Biology An Introduction to Pathology (3rd ed). US: StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK482489/?report

Kim, H., Baek, C. H., Lee, R. B., Chang, J. W., Yang, W. S., & Lee, S. K. (2017). Anti-Fibrotic Effect of Losartan, an Angiotensin II Receptor Blocker, Is Mediated through Inhibition of ER Stress via Up-Regulation of SIRT1, Followed by Induction of HO-1 and Thioredoxin. International Journal of Molecular Sciences, 18(2), Article 305. https://doi.org/10.3390/ijms18020305

Latha, L. Y., Darah, I., Jain, K., & Sasidharan, S. (2010). Toxicity study of Vernonia cinerea. Pharmaceutical Biology, 48(1), 101–104. https://doi.org/10.3109/13880200903046203

Leelaprakash, G. Mohan Dass, S., & Sivajothi, V. (2011). Antioxidant and hepatoprotective activities of Vernonia cinerea extract against CCL4 induced hepatotoxicity in albino rats. International Journal of Pharmaceutical Sciences Review and Research, 10(2). Article 5. https://globalresearchonline.net/journalcontents/volume10issue2/Article-005.pdf

Leelavathi, L., Sushanthi, S., Rajeshkumar, S., Meignana Arumugham, I., & Jayaseelan, V.P. (2023). In Vitro Biological Activity of Aqueous Extract of Cyanthillium Cinereum Against Oral Pathogens. Journal of Population Therapeutics and Clinical Pharmacology, 30(6), Article e94-e101. https://doi.org/10.47750/jptcp.2023.30.06.013

Liu, Y., Tian, F., Shan, J., Gao, J., Li, B., Lv, J., ... & Ma, X. (2020). Kupffer Cells: Important Participant of Hepatic Alveolar Echinococcosis. Frontiers in Cellular and Infection Microbiology, 10, Article 8. https://doi.org/10.3389/fcimb.2020.00008

Liu, T., Zhang, L., Joo, D., & Sun, S. C. (2017). NF-κB signaling in inflammation. In Signal Transduction and Targeted Therapy, 2. Springer Nature. https://doi.org/10.1038/sigtrans.2017.23

Loguercio, C., & Festi, D. (2011). Silybin and the liver: From basic research to clinical practice. World Journal of Gastroenterology, 17(18), 2288-2301. https://doi.org/10.3748/wjg.v17.i18.2288

Mayer, B. (2014). How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century. Archives of Toxicology, 88(1), 5–7. https://doi.org/10.1007/s00204-013-1127-0

Mazumder, U. K., Gupta, M., Manikandan, L., Bhattacharya, S., Haldar, P. K., & Roy, S. (2003). Evaluation of anti-inflammatory activity of Vernonia cinerea less. extract in rats. Phytomedicine, 10(2-3), 185-188. https://doi.org/10.1078/094471103321659915

Moesan, K., Phetnoi, K., Buathong, N., Chariyavilaskul, P., Wattanavijitkul, T., & Sukarnjanaset, W. (2024). Nicotine Gum in Thai Smokers with Different CYP2A6 Enzymes: A Population Pharmacokinetic Analysis. Siriraj Medical Journal, 76(8), 504–513. https://doi.org/10.33192/smj.v76i8.267636

Monton, C., Chankana, N., Suksaeree, J., Duangjit, S. (2023). Impact of Solvent-to-Solid Ratio and Infusion Duration on Extraction Yield and Nitrate Content of Cyanthillium cinereum (L.) H.Rob. and Clausena anisata (Willd.) Hook.f. ex Benth.: An Optimization Approach. Interprofessional Journal of Health Sciences, 21(1-2), Article IJHS-0239. Available from: https://li05.tci-thaijo.org/index.php/IJHS/article/view/239

Musial, C., Kuban-Jankowska, A., & Gorska-Ponikowska, M. (2020). Beneficial properties of green tea catechins. International Journal of Molecular Sciences, 21(5), Article 1744. https://doi.org/10.3390/ijms21051744

Neuman, M. G., Cohen, L., Opris, M., Nanau, R. M., Hyunjin, J. (2015). Hepatotoxicity of Pyrrolizidine Alkaloids. Journal of Pharmaceutical Sciences, 18(4), 825-843. https://doi.org/10.18433/j3bg7j

Panossian, A., & Wikman, G. (2008). Pharmacology of Schisandra chinensis Bail.: An overview of Russian research and uses in medicine. Journal of Ethnopharmacology, 118(2), 183-212. https://doi.org/10.1016/j.jep.2008.04.020

Pfingstgraf, I. O., Taulescu, M., Pop, R. M., Orăsan, R., Vlase, L., Uifalean, A., ... & Pârvu, A. E. (2021). Protective Effects of Taraxacum officinale L. (Dandelion) Root Extract in Experimental Acute on Chronic Liver Failure. Antioxidants (Basel), 10(4), Article 504. https://doi.org/10.3390/antiox10040504

Picciotto, M. R., Caldarone, B. J., King, S. L., & Zachariou, V. (2000). Nicotinic Receptors in the Brain: Links between molecular biology and behavior molecular biology and neurophysiology of nAChRs. Neuropsychopharmacology, 22(5), 451-465. https://doi.org/10.1016/S0893-133X(99)00146-3

Pratheeshkumar, P., & Kuttan, G. (2011). Protective role of Vernonia cinereal L. against gamma radiation induced immunosupression and oxidative stress in mice. Human and Experimental Toxicology, 30(8), 1022-1038. https://doi.org/10.1177/0960327110385959

Sansone, L., Milani, F., Fabrizi, R., Belli, M., Cristina, M., Zagà, V., ... & Russo, P. (2023). Nicotine: From Discovery to Biological Effects. International Journal of Molecular Sciences, 24(19), Article 14570. https://doi.org/10.3390/ijms241914570

Singh, S., & Sharma, B. (2011). Hepatoprotective Effect of Curcumin on Lindane-induced Oxidative Stress in Male Wistar Rats. Toxicology International, 18(2), 124-129. https://doi.org/10.4103/0971-6580.84264

Slevin, E., Baiocchi, L., Wu, N., Ekser, B., Sato, K., Lin, E., ... & Meng, F. (2020). Kupffer Cells: Inflammation Pathways and Cell-Cell Interactions in Alcohol-Associated Liver Disease. The American Journal of Pathology, 190(11), 2185-2193. https://doi.org/10.1016/j.ajpath.2020.08.014

Soeda, J., Morgan, M., McKee, C., Mouralidarane, A., Lin, C., Roskams, T., & Oben, J. A. (2012). Nicotine induces fibrogenic changes in human liver via nicotinic acetylcholine receptors expressed on hepatic stellate cells. Biochemical and Biophysical Research Communications, 417(1), 17-22. https://doi.org/10.1016/j.bbrc.2011.10.151

Sonibare, M. A., Aremu, O. T., & Okorie, P. N. (2016). Antioxidant and antimicrobial activities of solvent fractions of Vernonia cinerea (L.) Less leaf extract. African Health Sciences Journal, 16(2), 629-639. https://doi.org/10.4314/ahs.v16i2.34

Srithanee, K., Ruttanatam, P., Loachai, S., & Puchomkaeo, R. (2022). The effectiveness of Ya Dok Khao (Vernonia cinerea (L.) Less.) herbal products in reducing smoking behavior of people in Ban Kham Pa-O community, Kuddon sub-district, Huai Mek district, Kalasin Province. SciTech Research Journal, 5(1), 29–48. https://ph02.tci-thaijo.org/index.php/jstrmu/article/view/246383

Teerapong, S., Faisaikarm, T., Nimsanor, N., Changsangfa, C., Promthep, K., & Saikhun, K. (2019). Effect of nicotine on gene expression and developmental competence of bovine oocytes. The Thai Journal of Veterinary Medicine, 49(1), 43–48. https://he01.tci-thaijo.org/index.php/tjvm/article/view/193682

Trang, N. M., Vinh, L. B., Phong, N. V., Yang, S. Y. (2024). Traditional Uses, Phytochemistry, and Pharmacological Activities of Vernonia cinerea (L.) Less.: An Updated Review. Nutrients, 16(9), Article 1396. https://doi.org/10.3390/nu16091396

Van Rossum, T. G., Vulto, A. G., de Man, R. A., Brouwer, J. T., & Schalm, S. W. (1998). Review article: glycyrrhizin as a potential treatment for chronic hepatitis C. Alimentary Pharmacology & Therapeutics, 12(3), 199-205. https://doi.org/10.1046/j.1365-2036.1998.00