## 3 Results
On the other hand, the formulation of butein-chitosan did not show the predicted synergistic glucose-lowering activity [55]. Chlorogenic acid is a naturally occurring compound isolated from _Cecropia obtusifolia_ that can exert many beneficial health effects, like anticarcinogenic, neuroprotective, antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic properties. In this context, a survey explored whether chlorogenic acid can act as an insulin secretory agent by increasing the concentration of intracellular calcium ([Ca2+] in RINm5F cells and as an insulin sensitizer and lipid-lowering factor by triggering PPAR-\(\gamma\) and PPAR-\(\alpha\) expression, respectively, in the 3T3-L1 adipocyte cells [56]. RINm5F cells exposed to a concentration of 200 uM chlorogenic acid were characterized by a nine-times enhancement in [Ca2+]i in comparison with the controls and four-times in comparison with the positive controls. An enhancement in insulin release was also found analogously to that of the positive controls. Chlorogenic acid also considerably enhanced the PPAR-\(\gamma\) and GLUT4 mRNA expression as well as PPAR-\(\alpha\) and fatty acid translocase protein (FATP) [56]. Furthermore, a chemoinformatic analysis supported the evidence that chlorogenic acid may have appropriate physicochemical characteristics to be regarded as a lead bioactive for the design of novel drug candidates with analogous activities. Collectively, these findings suggest that chlorogenic acid has multiple modes of activity for developing potential efficient therapies for metabolic diseases like diabetes [56]. The hypocholesterolemic and hepatoprotective effects of chlorogenic acid intake were also explored by assessing the plasma lipid profile (total cholesterol, triglycerides, HDL, and LDL) in rats provided a normal diet, a cholesterol-rich diet, or a cholesterol-rich diet including a chlorogenic acid supplement [57]. The chlorogenic acid significantly changed the hypercholesterol diet-induced elevations in plasma total cholesterol and LDL, whereas it decreased the HDL with dose-dependent improvements in the atherogenic index and cardiovascular risk factors [57]. The lipid deposition in the liver was considerably reduced in hypercholesterol animals exposed to chlorogenic acid. The hypocholesterolemic activity of the chlorogenic acid was ascribed to enhanced hepatic fatty acid catabolism via upregulation of PPAR-\(\alpha\) mRNA expression [57]. A study by [PERSON] et al. explored dehydrodiabetic acid, a natural molecule contained in pine wood and rosin, assessing whether it could stimulate PPAR-\(\gamma\) and PPAR-\(\alpha\) to reduce insulin resistance and liver steatosis in high-fat diet (HFD)-fed mice [58]. Dehydroahetic acid was found to bind to PPAR-\(\gamma\) and PPAR-\(\alpha\) LBDs by stable hydrogen bonds. Dehydroahetic acid has also been shown to promote 3T3-L1 differentiation by activating PPAR-\(\gamma\) and stimulating oxygen uptake in mitochondria in HL7702 cells through PPAR-\(\alpha\) motivation [58]. In HFD-fed mice, dehydrodiabetic acid administration reduced glucose intolerance and insulin resistance and lowered liver steatosis, biomarkers of hepatic damage (alanine aminotransferase--ALT; aspartate aminotransferase--AST), and lipid accumulation [58]. Moreover, dehydrodiabetic acid induced PPAR-\(\gamma\) and PPAR-\(\alpha\) mRNA signaling factorsparticipating in insulin sensitivity and fat metabolism, in vitro and in vivo, and downregulated the mRNA expression of the modulators involved in inflammation [58]. Therefore, dehydrodiabetic acid may be a dual PPAR-\(\alpha\)/\(\gamma\) and PPAR-\(\gamma\) partial agonist. It is also able to alleviate insulin resistance and liver steatosis caused by HFD intake in mice [58]. Pelargonidin constitutes a naturally occurring molecule that is commonly found in fruits. It exerts diverse beneficial properties against oxidation, atherosclerosis, inflammation, hyperglycemia, and diabetes disease states. A study by [PERSON] et al.