Anti-Obesity Effects of Cissus Quadrangularis (Cissuslean®) in C57bl/6j Mice with High-Fat-Diet Induced Obesity and 3t3-L1 Adipocytes

Sudhanva M S¹, Akhina Tom², Firoz H M², Zayeem Firoz Hussain³, Sadashiva CT^2, and Shobith Rangappa^1,

¹Adichunchanagiri Institute for Molecular Medicine, Adichunchanagiri University, B G Nagara- 571 448, Mandya

²Department of Research and Development, Star Hi Herbs Pvt Ltd, Jigani, Bangalore-560105, Karnataka, India

³Department of Biotechnology, The Oxford College of Engineering, Bangalore, Karnataka, India

Cite this paper:
Sudhanva M S, Akhina Tom, Firoz H M, Zayeem Firoz Hussain, Sadashiva CT and Shobith Rangappa. Anti-Obesity Effects of Cissus Quadrangularis (Cissuslean®) in C57bl/6j Mice with High-Fat-Diet Induced Obesity and 3t3-L1 Adipocytes. Journal of Food and Nutrition Research. 2025; 13(1):9-17. doi: 10.12691/jfnr-13-1-2

Abstract

Obesity is gradually becoming a widespread health problem, and treatment using natural compounds has seen an increasing trend. The aim of this study investigated the effects and underlying mechanisms of Cissus quadrangularis (Cissuslean®) on adipogenesis and high-fat diet (HFD)-induced obesity. The inhibitory effects of Cissuslean® on adipocyte differentiation were evaluated in vitro using 3T3-L1 preadipocyte cells, focusing on AMPK signaling and lipid metabolism. Subsequently, an in vivo trial with male C57BL/6J mice fed HFD was conducted to examine the effects of Cissuslean® at 25, 50, and 100 mg/kg on adipose tissue characteristics, body weight, fat mass, and obesity-related gene expression. Cissuslean® significantly inhibited preadipocyte differentiation by reducing intracellular lipid accumulation and suppressing the expression of key adipogenic regulators. It also enhanced AMPK phosphorylation during early adipocyte differentiation. In HFD-induced obese mice, Cissuslean® administration resulted in marked reductions in body weight gain, adipose tissue mass, and hepatic lipid accumulation. Furthermore, decreased serum ALT and AST levels indicated attenuation of HFD-induced hepatic injury. According to these results, Cissuslean® reduces body fat mass by inhibiting lipase activity and regulating genes and proteins involved in adipogenesis and lipogenesis in epididymal adipose tissue. Our results suggest that Cissuslean® may be used as an anti-obesity agent.

Keywords:
Anti-obesityCissus quadrangularisCissuslean® DEXAhigh-fat diet

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Figures

References:

[1]	Lin, X., Li, H, Obesity: Epidemiology, Pathophysiology, and Therapeutics. Front Endocrinol (Lausanne).12, 706978. Sep. 2021.
[2]	WHO. Obesity and overweight. Available online: www.who.int/ mediacentre/factsheets/fs311/en/2021(cited 2022 August).
[3]	World Health Organization. World Obesity Day 2022 – Accelerating action to stop obesity. https:// www.who.int/ news/item/04-03-2022-world-obesity-day-2022-accelerating-action-to-stop-obesity (4 March 2022).
[4]	Jiang, J., Cai X., Pan Y., Du X., Zhu H., Yang X., Zheng D., Gaisano H., Wei T., He Y, Relationship of obesity to adipose tissue insulin resistance. BMJ Open Diabetes Res Care. 8(1), e000741. Apr. 2020.
[5]	Shaik Mohamed Sayed UF., Moshawih, S., Goh, H.P., Kifli, N., Gupta, G., Singh, S.K., Chellappan DK., Dua K., Hermansyah A., Ser H.L., Ming L.C., Goh B.H, Natural products as novel anti-obesity agents: insights into mechanisms of action and potential for therapeutic management. Front Pharmacol. 14, 1182937. Jun. 2023.
[6]	Chopra SS, Patel MR, Gupta LP, Datta IC. Studies on Cissusquadrangularis in experimental fracture repair: effect on chemical parameters in blood. Indian J Med Res. 63(6), 824-8. Jun. 1975.
[7]	Oben, J., Kuate, D., Agbor, G., Momo, C., Talla ,X, The use of a Cissusquadrangularis formulation in the management of weight loss and metabolic syndrome. Lipids Health Dis. 5, 24. Sep. 2006.
[8]	Bhujade, A.M., Talmale, S., Kumar, N., Gupta, G., Reddanna , P., Das, S.K., Patil, M.B, Evaluation of Cissusquadrangularis extracts as an inhibitor of COX, 5-LOX, and proinflammatory mediators. J Ethnopharmacol, 141(3), 989-96. Jun. 2012.
[9]	Mehta M, Kaur N, Bhutani KK. Determination of marker constituents from Cissusquadrangularis Linn. and their quantitation by HPTLC and HPLC. PhytochemAnal.12 (2),91-5.Mar-Apr. 2001.
[10]	Sharp, Hazel &Hollinshead, Jackie & Bartholomew, Barbara &Oben, Julius & Watson, Alison & Nash, Robert. Inhibitory effects of Cissusquadrangularis L. derived components on lipase, amylase and alpha-glucosidase activity in vitro. Natural product communications, 2, 817-822. 2019.
[11]	Kopelman, P.G. Obesity as a medical problem. Nature 2000, 404, 635–43.
[12]	Choi, J.S., Kim, J.H., Ali, M.Y., Min, B.S., Kim, G.D., Jung, H.A, Coptischinensis alkaloids exert anti-adipogenic activity on 3T3-L1 adipocytes by downregulating C/EBP-α and PPAR-γ. Fitoterapia. 98, 199-208. Oct. 2014.
[13]	Zeng XY, Zhou X, Xu J, Chan SM, Xue CL, Molero JC, Ye JM. Screening for the efficacy on lipid accumulation in 3T3-L1 cells is an effective tool for the identification of new anti-diabetic compounds. BiochemPharmacol. 84(6), 830-7. Sep. 2012.
[14]	Jung, C.H.; Jang, S.J.;Ahn, J.;Gwon, S.Y.;Jeon,T.-I.; Kim, T.W.; Ha, T.Y. Alpiniaofficinarum inhibits adipocyte differentiation and high-fat diet–induced obesity in micethrough regulation of adipogenesis and lipogenesis. J. Med. Food. 15, 959–967. 2012.
[15]	Yang, J.-W.; Kim, S.S. GinsenosideRc promotes anti-adipogenic activity on 3T3-L1adipocytes by down-regulating C/EBPα and PPARγ, Molecules20, 1293–1303. 2015.
[16]	Song, Y., Park, H.J,, Kang, S.N., Jang, S.H., Lee, S.J., Ko, Y.G., Kim, G.S., Cho, J.H, Blueberry peel extracts inhibit adipogenesis in 3T3-L1 cells and reduce high-fat diet-induced obesity. PLoS One8 (7), e69925. Jul. 2013.
[17]	Jeon, T., Hwang, S.G., Hirai, S., Matsui, T., Yano, H., Kawada, T., Lim, B.O., Park, D.K, Red yeast rice extracts suppress adipogenesis by down-regulating adipogenic transcription factors and gene expression in 3T3-L1 cells. Life Sci. 75(26),.3195-203. Nov. 2004.
[18]	Otto, T.C., Lane, M, Adipose development: from stem cell to adipocyte. Crit Rev BiochemMol Biol. 40(4), 229-42. 2005 Jul-Aug.
[19]	Spiegelman, B.M., Flier, J.S, Obesity and the regulation of energy balance. Cell104 (4), 531-43. 2001 Feb.
[20]	Trigueros, L., Peña, S., Ugidos, A.V,, Sayas-Barberá, E., Pérez-Álvarez, J.A., Sendra, E, Food ingredients as anti-obesity agents: a review. Crit Rev Food SciNutr. 53(9), 929-42. 2013.
[21]	Dulloo, A.G, The search for compounds that stimulate thermogenesis in obesitymanagement: From pharmaceuticals to functional food ingredients. Obes. Rev. 12,866–883. 2011.
[22]	Park, Y.H., Lee, J.J., Son, H.K., Kim, B.H., Byun, J., Ha, J.H, Antiobesity Effects of Extract from Spergularia marina Griseb in Adipocytes and High-Fat Diet-Induced Obese Rats. Nutrients. 12(2), 336. Jan. 2020.
[23]	Choi, B.R., Kim, H.J., Lee, Y.J., Ku, S.K, Anti-Diabetic Obesity Effects of Wasabia Japonica Matsum Leaf Extract on 45% Kcal High-Fat Diet-Fed Mice. Nutrients. 12(9), 2837. Sep. 2020.
[24]	Kirtikar, K.R., Basu, B.D., Basu, L.M, Indian Medicinal Plants, 3rd ed.; Lalit Mohan Basu:Allahabad, India, 2000.
[25]	Greenberg, A.S., Obin, M.S, Obesity and the role of adipose tissue in inflammation andmetabolism. Am. J. Clin. Nutr83, 461–465.2006.
[26]	Kim, J.Y., Nolte, L.A., Hansen, P.A., Han, D.H., Ferguson, K., Thompson, P.A., Holloszy, J.O, High-fat diet-induced muscle insulin resistance: relationship to visceral fat mass. Am J PhysiolRegulIntegr Comp Physiol. 279(6), R2057-65. Dec. 2000.
[27]	de, Jong, J.M., Larsson, O., Cannon, B., Nedergaard, J, A stringent validation of mouseadipose tissue identity markers. Am. J. Physiol. Endocrinol. Metab. 308, E1085–E1105.2015.
[28]	Tilg, H., Moschen, A.R, Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nature reviews. Immunology. 6(10), 772-783. Oct. 2006.
[29]	Aguila, M.B., Mandarim-de-Lacerda, C.A, Heart and blood pressure adaptations in Wistar rats fed with different high-fat diets for 18 months. Nutrition. 19(4), 347-52. Apr. 2003.
[30]	Tripathy, D., Mohanty, P., Dhindsa, S., Syed, T., Ghanim, H., Aljada, A., Dandona, P, Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects. Diabetes. 52(12), 2882-7. Dec. 2003.
[31]	Mopuri, R., Ganjayi, M., Banavathy, K.S, Evaluation of anti-obesity activities of ethanolic extract of Terminaliapaniculata bark on high fat diet-induced obese rats. BMC Complement Altern Med 15, 76 (2015).