Zyflamend Inhibits Adipogenesis: A mechanistic study evaluating the impact of phytonutrients on adipocyte differentiation

Zyflamend, a polyphenol herbal supplement, includes numerous different extracts. This botanical complex has been used as a natural anti-inflammatory due to its impact on COX-2. More recently, research has exhibited its potential as an anti-cancer agent. Currently, the effects of Zyflamend in non-cancer cells, specifically adipocytes, has yet to be explored. Due to Zyflamend's ability to promote activation of AMPK, it may prove relevant to study the potential interactions with cells treated with Zyflamend during differentiation, a metabolically involved process. This study sought to determine the impact of Zyflamend on non- cancer cells such as 3T3-L1 adipocytes during differentiation and identify the mechanisms involved. Zyflamend was shown to effectively and significantly attenuate adipogenesis by downregulating markers of lipogenesis, decreasing glucose uptake by downregulating GLUT4, and upregulating hormone-sensitive lipases. These effects halted differentiation of 3T3-L1 cells and altered their metabolic dynamic. As evidenced in previous research, Zyflamend was found to increase phosphorylation AMPK, affecting fatty acid metabolism. Furthermore, an upregulation of PKA-regulated lipolysis through pHSLS660 was unexpectedly observed. In addition, Zyflamend drastically increased activity of JNK. Through investigation of these effects, partial rescue of adipogenesis was observed through treatments with PKA inhibitor H89 and AMPK inhibitor BML275; however, the presence of JNK inhibitor SP600125 showed the strongest rescue over the effects of Zyflamend on differentiation. These results suggest Zyflamend's effect on attenuating adipogenesis may be modulated in part by upregulation of JNK and PKA. The ability of Zyflamend to attenuate the adipogenesis process suggest a potential to target cell differentiation mechanisms relevant to energy metabolism.