## 3 Results
In this context, the function of HKC as a dual PPAR-\(\alpha\)/\(\gamma\) ligand was assessed in a survey investigating its antidiabetic effects on renal impairment in male Sprague-Dawley rats [66]. For this purpose, rats with diabetes-related nephropathy received HKC for 12 weeks at three different dosages: a high dosage (300 mg/kg/d), a medium dosage (175 mg/kg/d), and a low dosage (75 mg/kg/d). It was found that HKC diminished the ER/c-Jun NH2-terminal kinase action in the hepatic and renal tissues of diabetic nephropathy rats and then ameliorated kidney damage by activating PPAR-\(\alpha\)/\(\gamma\)[66]. These findings provide strong evidence that HKC may have potential as an antidiabetic nephropathy factor for the therapy of diabetic nephropathy in humans through the activation of PPAR-\(\alpha\)/\(\gamma\)[66]. Hyperin is a flavonoid substance that is found in a variety of plants, such as _Ericaceae_, _Guttifera_, and _Celastraceae_. [PERSON] et al. showed that it is characterized by several pharmacological properties such as antioxidant, anti-cancer, anti-coagulant, and anti-inflammatory activities [67]. In a comprehensive study, hyperin substantially diminished the inflammatory levels in C57 BL/6J mice with acute hepatic damage and lowered the TNF-\(\alpha\) and IL-6 expression in LPS-exposed RAW264.7 cells [67]. Likewise, this study revealed that hyperin significantly stimulated PPAR-\(\gamma\) expression in vivo and in vitro. Interestingly, a specific blocker of PPAR-\(\gamma\) T0070907 and PPAR-\(\gamma\) small interfering (si)-RNA-facilitated silencing in RAW264.7 cells were utilized in comparison to the hyperin treatment group to assess the contribution of hyperin in improving LPS-induced inflammation [67]. Notably, in the LPS-exposed RAW264.7 cells, PPAR-\(\gamma\) overexpression after hyperin administration had an opposite effect on the TNF-\(\alpha\) and IL-6 levels. In addition, P-ERK1/2 and P-P38 MAPK were significantly suppressed by hyperin [67]. Taken together, all the above results supported that hyperin could be considered a useful PPAR-\(\gamma\) modulator, decreasing ERK1/2 and p38 MAPK throughout the inflammatory process [67]. [PERSON] et al. examined the effect of natural molecules on adopophilin [perilipin 2, (PLIN2)] levels, a recognized target of PPAR-\(\gamma\)[68]. In a recent study, PPAR-\(\gamma\) antagonist 2-chloro-5-nitro-N-phenylbenzamide (GW9662) was used to verify whether natural compounds can control PLIN2 expression through PPAR-\(\gamma\)[68]. Surprisingly, the PLIN2 expression was upregulated at a concentration-dependent level by GW9662 rather than opposing the upregulation of PLIN2 expression in THP-1 macrophages [68]. In many human and mice macrophage cell models, this unexpected upregulation was also found to occur [56]. GW9662 increased lipogenesis and increased the TG levels in line with the upregulation of PLIN2 protein. Finally, PPAR\(\beta\)/\(\delta\) was identified as a substantial agent of the above important GW9662 actions [68]. Phydol, a diterpene alcohol that is included in the chlorophyll molecule, is implicated in the energy assembly from light. As approximately all photosynthetic organisms utilize chlorophylls, phytol is widely found in nature among diverse vegetables [69]. Phytanic acid was shown to stimulate PPAR-\(\gamma\) and RXR, promoting cellular differentiation in both white and brown adipose tissue [70]. Additionally, phytanic acid can stimulate PPAR-\(\alpha\), affecting lipid metabolism in certain cell categories [71]. Phytanic acid can additionally be delivered from the transformation of dietary phytol in the human body [72]. Moreover, a phytol-enriched diet was found to elevate the plasma and liver amounts of phytanic acid and stimulate the mRNA levels of the PPAR-\(\alpha\) target genes implicated in peroxisomes and mitochondria \(\beta\)-oxidation and fatty acid metabolism [73]. Another study examined whether _hydroxysafflower_ may exert protective effects against liver fibrosis [74].