Volume: 44 Issue: 1
Year: 2024, Page: 65-70, Doi: https://doi.org/10.51248/.v44i1.4066
Received: Jan. 21, 2024 Accepted: Feb. 28, 2024 Published: May 1, 2024
Introduction and Aim: The incidence of non-alcoholic fatty liver disease is increasing steadily across the global population. NAFLD may progress to the more serious non-alcoholic steatohepatitis (NASH), a condition that can subsequently advance to fibrosis, cirrhosis, and in many cases, to hepatocellular carcinoma (HCC). There are currently no drugs approved by the FDA for the treatment of NAFLD. We previously reported the remarkable therapeutic potency of Utt-B, a saponin isolated in our lab, from the leaves of Solanum nigrum Linn (S. nigrum), against hepatocellular carcinoma (HCC). In the current study, we have investigated the therapeutic efficacy of Utt-B against NAFLD, which eventually leads to NASH.
Materials and Methods: HepG2 cells were used for in vitro experiments. MTT assay, Oil Red O staining and Immunoblotting were used to evaluate the hepatoprotective and therapeutic effects of Utt-B against NAFLD.
Results: Utt-B treatment effectively reduced lipid droplet accumulation within HepG2 cells, demonstrating its potential in mitigating fat deposition associated with NAFLD. Utt-B activated AMPK signaling, leading to the down-regulation of FASN, a key enzyme regulating lipogenesis, suggesting its ability to modulate pathways involved in lipid metabolism.
Conclusion: Our results highlight Utt-B as a promising therapeutic agent for metabolic liver disorders, including NAFLD and NASH, warranting further exploration of the molecule in clinical settings.
Keywords: NAFLD; NASH; lipogenesis; AMPK; liver disease
1. Allen, A.M., Therneau, T.M., Ahmed, O.T., Gidener, T., Mara, K.C., Larson, J.J., et al., Clinical course of non-alcoholic fatty liver disease and the implications for clinical trial design. Journal of Hepatology. 2022;77(5):1237-1245.
2. Marchisello, S., Di Pino, A., Scicali, R., Urbano, F., Piro, S., Purrello, F., et al., Pathophysiological, molecular and therapeutic issues of nonalcoholic fatty liver disease: an overview. International Journal of Molecular Sciences. 2019; 20(8):1948.
3. Tanaka, N., Kimura, T., Fujimori, N., Nagaya, T., Komatsu, M., Tanaka, E. Current status, problems, and perspectives of non-alcoholic fatty liver disease research. World Journal of Gastroenterology. 2019;25(2):163.
4. Ampofo, A.G., Boateng, E.B. Beyond 2020: Modelling obesity and diabetes prevalence. Diabetes Research and Clinical Practice. 2020;167:108362.
5. Chakraborty, S., Ganie, M.A., Masoodi, I., Jana, M., Gupta, N., Sofi, N.Y. Fibroscan as a non-invasive predictor of hepatic steatosis in women with polycystic ovary syndrome. The Indian Journal of Medical Research. 2020;151(4):333.
6. Nath, L.R., Gorantla, J.N., Thulasidasan, A.K.T., Vijayakurup, V., Shah, S., Anwer, S., et al., Evaluation of uttroside B, a saponin from Solanum nigrum Linn, as a promising chemotherapeutic agent against hepatocellular carcinoma. Scientific Reports. 2016;6(1):36318.
7. Nath, L.R., Swetha, M., Vijayakurup, V., Thangarasu, A.K., Haritha, N.H., Shabna, A., et al., Blockade of uttroside b-induced autophagic pro-survival signals augments its chemotherapeutic efficacy against hepatocellular carcinoma. Frontiers in Oncology. 2022;12:812598.
8. Swetha, M., Keerthana, C.K., Rayginia, T.P., Nath, L.R., Haritha, N.H., Shabna, A., et al., Augmented efficacy of uttroside B over sorafenib in a murine model of human hepatocellular carcinoma. Pharmaceuticals. 2022;15(5):636.
9. Krithika, R., Verma, R.J. Solanum nigrum confers protection against CCl4-induced experimental hepatotoxicity by increasing hepatic protein synthesis and regulation of energy metabolism. Clinical Phytoscience. 2019;5(1):1-8.
10. Chang, J.J., Chung, D.J., Lee, Y.J., Wen, B.H., Jao, H.Y., Wang, C.J. Solanum nigrum polyphenol extracts inhibit hepatic inflammation, oxidative stress, and lipogenesis in high-fat-diet-treated mice. Journal of Agricultural and Food Chemistry. 2017;65(42):9255-9265.
11. Wang, K., Li, C., Lin, X., Sun, H., Xu, R., Li, Q., et al., Targeting alkaline ceramidase 3 alleviates the severity of nonalcoholic steatohepatitis by reducing oxidative stress. Cell Death & Disease. 2020;11(1):28.
12. Gu, D., Yu, B., Zhao, C., Ye, W., Lv, Q., Hua, Z., et al., The effect of pleiotrophin signaling on adipogenesis. FEBS letters. 2007;581(3):382-388.
13. Li, W., Saud, S.M., Young, M.R., Chen, G., Hua, B. Targeting AMPK for cancer prevention and treatment. Oncotarget. 2015; 6(10):7365.
14. Ng, C.H., Huang, D.Q., Nguyen, M.H. Nonalcoholic fatty liver disease versus metabolic-associated fatty liver disease: Prevalence, outcomes and implications of a change in name. Clinical and Molecular Hepatology. 2022;28(4):790.
15. Pouwels, S., Sakran, N., Graham, Y., Leal, A., Pintar, T., Yang, W., et al., Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss. BMC Endocrine Disorders. 2022;22(1):1-9.
16. Keerthana, C.K., Rayginia, T.P., Shifana, S.C., Anto, N.P., Kalimuthu, K., Isakov, N, et al., The role of AMPK in cancer metabolism and its impact on the immunomodulation of the tumor microenvironment. Frontiers in Immunology. 2023;14: 1114582.
17. Choi, Y.K., Park, K.G. Metabolic roles of AMPK and metformin in cancer cells. Molecules and cells. 2013;36:279-287.
18. Liu, S., Jing, F., Yu, C., Gao, L., Qin, Y,. Zhao, J. AICAR-induced activation of AMPK inhibits TSH/SREBP-2/HMGCR pathway in liver. PLoS One. 2015;10(5):e0124951.
Tennyson P. Rayginia, Chenicheri K. Keerthana, Sadiq C. Shifana, Sreekumar U. Aiswarya, Retnakumari Archana P, Maria Joy P, Ravi S. Lankalapalli, Kuzhuvelil B. Harikumar, Ruby John Anto. Evaluation of Uttroside B, a potent bioactive from Solanum nigrum Linn, as a candidate drug molecule against non-alcoholic fatty liver disease. Biomedicine: 2024; 44(1): 65-70