## 3 Results
The findings were negated by the treatment with GW9662, indicating that auraptene may exert the above beneficial effects by activating PPAR-\(\gamma\)[80]. It is likely that auraptene may control the mRNA expression of both PPAR-\(\gamma\) and PPAR-\(\alpha\) target genes. These activities may contribute to the effects of citrus fruits on cardiovascular disease [80]. Furthermore, a natural pigment widely utilized in various processed foodstuffs is anantto, which is extracted from the outer layer of _Bixa urellana_ seeds [81]. Both bixin and norbixin, which belong to the carotenoid phytochemical class, are principal ingredients of anntto that can exert antioxidant and anticarcinogenic activities [82]. The anntto extracts and norbixin exerted hypoglycemic properties in non-obese dogs and mice, respectively [83; 84]. Moreover, it was shown that bixin and norbixin triggered PPAR-\(\gamma\) and bixin stimulated PPAR-\(\gamma\) target genes in 3T3-L1 adipocytes, resulting in enhanced adipose tissue cellular differentiation and insulin-induced glucose treatment [85]. Therefore, PPAR-\(\gamma\) activation may be responsible for the hypoglycemic effects of anntto and norbixin. Certain polychlorinated compounds called chlorophellins A-C were extracted from the fungus _Phellinus ribis_[86], together with the recognized compound drosophilin A, in an attempt to find naturally occurring compounds that can activate PPAR-\(\gamma\). Nuclear magnetic resonance (NMR) and mass spectrometry were applied to assign their chemical structures. Chlorophellin C was the strongest PPAR-\(\gamma\) agonist. It exerted rather similar PPAR-\(\gamma\) agonistic activity to that of rosiglitazone, a common pharmacological agent applied for the treatment of diabetes [86]. Abscisic acid is a naturally occurring phytohormone and a promising PPAR-\(\gamma\) ligand that can substantially improve insulin sensitivity in db/db mice [87]. Indeed, [PERSON] et al. applied a loss-of-function methodology to explore if abscisic acid could ameliorate insulin resistance in a PPAR-\(\gamma\)-dependent manner on immunological cells. In db/db mice, ab-scisic acid significantly reduced the infiltration of CCR2(+) F4/80(hi) into white adipose tissue and inhibited the expression of MCP-1 in both white adipose tissue and plasma [87]. The PPAR-\(\gamma\) deficiency in immunological cells, such as macrophages, reduced the abscisic acid properties to suppress white adipose tissue F4/80(hi) ATM infiltration, inhibit MCP-1 expression, and attenuate glucose tolerance [87]. Several studies have shown that oleoylethanolamide, a natural fatty acid ethanolamide, stimulates satiety and suppresses weight increase in rats and mice by activating PPAR-\(\alpha\)[88; 89; 90]. PPAR-\(\alpha\) mRNA and its downstream genes were examined in another study. FAT/CD36, a fatty acid binding protein (L-FABP) in liver, and uncoupling protein-2 (UCP-2) were measured to investigate the possible molecular mechanisms that might reduce lipid buildup in Zucker rats exposed to oleoylethanolamide [91]. Indeed, a two-week administration of a reasonably reduced dosage of oleoylethanolamide (5 mg/kg, single dose daily, i.p.) substantially enhanced the levels of the 3 PPAR-\(\alpha\) target genes in the hepatic tissue of obese Zucker rats: _FAT/CD36, UCP-2_, and _L-FABP_[91]. Moreover, the protective role of ferulic acid and fish oil regarding gentamicin-induced nephrotoxicity in rats has been investigated in a recent study [92]. The pre- and co-administration of ferulic acid or fish oil attenuated the nephrotoxic impact of gentamicin, as reflected by the significant reductions in the serum blood urea nitrogen (BUN), creatinine, urinary albumin, and N-acetyl-beta-D-glucosamineaminidase (NAG) actions [92]. Both interventions significantly elevated the renal catalase (CAT) activity and PPAR-\(\gamma\) gene expression. Resolvin E1 was significantly raised in the fish oil group but not in the ferulic acid group [80].