The present study demonstrates a novel herbal formulation LI85008F inhibiting adipocyte differentiation and potentiates lipolysis in 3T3-L1 mouse adipocytes. LI85008F is formulated by combining extracts of three Indian herbs Moringa oleifera, Murraya koenigii and Curcuma longa. Oil red O staining of 3T3-L1 adipocytes reveals that LI85008F is a synergistic formulation that inhibits adipocyte differentiation in a dose dependent manner and concurrently down regulates the key adipogenic transcription factors Peroxisome Proliferator-Activated Receptor gamma (PPAR) and CCAAT/enhancer binding protein α (C/EBP). LI85008F confers significant reductions in intracellular triglyceride content in a dose dependent manner. Evidence suggests that LI85008F antagonizes PPAR through Ser112 phosphorylation via MAPK/ERK activation. Immunoblot analyses reveal that LI85008F treatment also down regulates the protein expressions of key PPAR responsive gene products such as Adipocyte differentiation related protein (ADRP), CD36, Adipocyte specific binding protein 2 (aP2) and perilipin. In differentiated adipocytes culture, LI85008F treatment results in significantly (p = 0.0169) increased lipolysis as measured by the release of glycerol. LI85008F does not exhibit cytotoxic effect on adipocytes. Taken together, the results suggest that LI85008F inhibits lipogenesis in adipocytes and concurrently antagonizes PPAR? and other lipogenic factors and in addition, potentiates triglyceride mobilization from the fat cells or enhances lipolysis.
S. R. Farmer and J. Auwerx, “Adipose Tissue: New Therapeutic Targets from Molecular and Genetic Studies: IASO Stock Conference 2003 Report,” Obesity Research, Vol. 5, No. 4, 2004, pp. 189-196. doi:10.1111/j.1467-789X.2004.00157.x
W. J. Lee, E. H. Koh, J. C. Won, M. S. Kim, J. Y. Park and K. U. Lee, “Obesity: The Role of Hypothalamic AMPactivated Protein Kinase in Body Weight Regulation,” The International Journal of Biochemistry & Cell Biology, Vol. 37, No. 11, 2005, pp. 2254-2259. doi:10.1016/j.biocel.2005.06.019
M. Chopra, S. Galbraith and I. Darnton-Hill, “A Global Response to a Global Problem: The Epidemic of over Nutrition,” Bulletin of the World Health Organization, Vol. 80, No. 12, 2002, pp. 952-958.
D. Rucker, R. Padwal, S. K. Li, C. Curioni and D. C. Lau, “Long Term Pharmacotherapy for Obesity and Overweight: Updated Meta Analysis,” BMJ, Vol. 335, No. 7631, 2007, pp. 1194-1199.
F. M. Gregore, C. M. Smas and H. S. Sul, “Understanding Adipocyte Differentiation,” Physiological Reviews, Vol. 78, No. 3, 1998, pp. 783-809.
J. M. Ntambi and K. Young-Cheul, “Adipocyte Differentiation and Gene Expression,” Journal of Nutrition, Vol. 130, No. 12, 2000, pp. 3122S-3126S.
S. Dev, “Ancient-Modern Concordance in Ayurvedic Plants: Some Examples,” Environmental Health Perspectives, Vol. 107, 1999, pp. 783-789. doi:10.1289/ehp.99107783
B. N. Sastri, “The Wealth of India-Raw Materials,” CSIR, New Delhi, 1962.
K. M. Nadkarni and A. K. Nadkarni, “The Indian Materia Medica,” Popular Prakasan, Bombay, 1976.
J. Dolly, K. R. Prashant, K. Amit, M. Shikha and W. Geeta, “Effect of Moringa oleifera Lam. Leaves Aqueous Extract Therapy on Hyperglycemic Rats,” Journal of Ethnopharmacology, Vol. 123, No. 3, 2009, pp. 392-396. doi:10.1016/j.jep.2009.03.036
P. Arulselvan and S. P. Subramanian, “Beneficial Effects of Murraya koenigii Leaves on Antioxidant Defense System and Ultra Structural Changes of Pancreatic Beta-Cells in Experimental Diabetes in Rats,” Chemico-Biological Interactions, Vol. 165, No. 2, 2007, pp. 155-164. doi:10.1016/j.cbi.2006.10.014
S. Yadav, V. Vats, Y. Dhunnoo and J. K. Grover, “Hypoglycemic and Anti-Hyperglycemic Activity of Murraya koenigii Leaves in Diabetic Rats,” Journal of Ethnopharmacology, Vol. 82, No. 2-3, 2002, pp. 111-116. doi:10.1016/S0378-8741(02)00167-8
I. Chattopadhyay, K. Biswas, U. Bandyopadhyay and R. K. Banerjee, “Turmeric and Curcumin: Biological Actions and Medicinal Applications,” Current Science, Vol. 87, No. 1, 2004, pp. 44-53.
K. Sengupta, J. N. Kolla, A. V. Krishnaraju, N. Yalamanchili, C. V. Rao, T. Golakoti, S. Raychaudhuri and S. P. Raychaudhuri, “Cellular and Molecular Mechanisms of Anti-Inflammatory Effect of Aflapin: A Novel Boswellia serrata Extract,” Molecular and Cellular Biochemistry, Vol. 354, No. 1-2, 2011, pp. 189-197. doi:10.1007/s11010-011-0818-1
H. Erding, K. J. Bum, S. Pasha and B. M. Spiegelman, “Inhibition of Adipogenesis through MAP Kinase-Mediated Phosphorylation of PPAR?,” Science, Vol. 27, Vol. 4, 1996, pp. 2100-2103.
H. S. Camp, A. Chaudhury and T. Leff, “A Novel Potent Antagonist of Peroxisome Proliferator-Activated Receptor Blocks Adipocyte Differentiation but Does Not Revert the Phenotype of Terminally Differentiated Adipocytes,” Endocrinology, Vol. 142, No. 7, 2001, pp. 3207-3213. doi:10.1210/en.142.7.3207
Y. Tanabe, M. Koga, M. Saito, Y. Matsunaga and K. Nakayama, “Inhibition of Adipocyte Differentiation by Mechanical Stretching through ERK-Mediated Downregulation of PPAR?,” Journal of Cell Science, Vol. 117, No. 16, 2004, pp. 3605-3614. doi:10.1242/jcs.01207
F. M. Gregoire, “Adipocyte Differentiation: From Fibro-Blast to Endocrine Cell,” Experimental Biology and Medicine, Vol. 226, No. 11, 2001, pp. 997-1002.
S. Rayalama, M. A. Della-Feraa and C. A. Bailea, “Phytochemicals and Regulation of the Adipocyte Life Cycle,” Journal of Nutrition Biochemistry, Vol. 19, No. 11, 2008, pp. 717-726. doi:10.1016/j.jnutbio.2007.12.007
M. Dell’Agli and E, Bosisio, “Biflavones of Ginkgo biloba Stimulate Lipolysis in 3T3-L1 Adipocytes,” Planta Medica, Vol. 68, No. 1, pp. 76-79. doi:10.1055/s-2002-19876
D. A. Moreno, N. Ilic, A. Poulev, D. L. Brasaemle, S. K. Fried and I. Raskin, “Inhibitory Effects of Grape Seed Extract on Lipases,” Nutrition, Vol. 19, No. 10, 2003, pp. 876-879. doi:10.1016/S0899-9007(03)00167-9
M. Mori and N. Hasegawa, “Superoxide Dismutase Activity Enhanced by Green Tea Inhibits Lipid Accumulation in 3T3-L1 Cells,” Phytotherapy Research, Vol. 17, No. 5, 2003, pp. 566-567. doi:10.1002/ptr.1182
F. M. Gregoire, C. M. Smas and H. S. Sul, “Understanding Adipocyte Differentiation,” Physiological Reviews, Vol. 78, No. 3, 1998, pp. 783-809.
P. Tontonoz, E. Hu and B. M. Spiegelman, “Regulation of Adipocyte Gene Expression and Differentiation by Peroxisome Proliferator Activated Receptor Gamma,” Current Opinion in Genetics & Development, Vol. 5, No. 5, 1995, pp. 571-576. doi:10.1016/0959-437X(95)80025-5
E. D. Rosen and B. M. Spiegelman, “Molecular Regulation of Adipogenesis,” Annual Review of Cell and Developmental Biology, Vol. 16, 2000, pp. 145-171. doi:10.1146/annurev.cellbio.16.1.145
M. Kimihiko, J. M. Peters and F. J. Gonzalez, “PPAR?/ ??Potentiates PPAR?-Stimulated Adipocyte Differentiation,” FASEB Journal, Vol. 18, No. 12, 2004, pp. 1477-1479.
A. V. Krishnaraju, D. Sundararaju, P. Srinivas, C. V. Rao, K. Sengupta and G. Trimurtulu, “Safety and Toxicological Evaluation of a Novel Anti-Obesity Formulation LI85008F in Animals,” Toxicology Mechanisms and Methods, Vol. 20, No. 2, 2010, pp. 59-68. doi:10.3109/15376510903483722
K. J. Soeder, S. K. Snedden, W. Cao, G. J. Della-Rocca, K. W. Daniel, L. M. Luttrell and S. Collins, “The 3-Adrenergic Receptor Activates Mitogen-activated Protein Kinase in Adipocytes through a Gi-Dependent Mechanism,” The Journal of Biological Chemistry, Vol. 274, No. 17, 1999, pp. 12017-12022.