## 3 Results
More specifically, it was found that _hydroxysafflower yellow A_ decreased carbon tetrachloride (CCI4)- and HFD-regulated hepatic fibrosis and decreased the serum biochemical indicator, decreased TIMP-1 and TGF-\(\beta\)1 expression, and increased PPAR-\(\gamma\) and matrix metallopeptidase-2 (MMP-2) expression [74]. The above outcomes were substantially decreased by the PPAR-\(\gamma\) antagonist GW9662 by preventing p38 MAPK phosphorylation [74]. These data highlight that both PPAR-\(\gamma\) and p38 MAPK signaling may exert critical preventive impacts against hepatic fibrogenesis and demonstrate a new potential role for _hydroxysafflower yellow A_ in the suppression of CCI4- and HFD-associated liver fibrosis [74]. Various terpenoids can activate PPAR-\(\gamma\) from 50 to 100 \(\upmu\)M [63]. In this regard, isogenous like geraniol, famesol, and geranylgeraniol were shown to exert a possible effect to stimulate PPAR-\(\gamma\) in 3T3-L1 adipocytes and HepG2 hepatocytes [75]. In the above assays, geranylgeraniol, famesol, and geranylgeraniol were 2.2, 4.1, and 3.7 times, respectively, greater than the vehicle controls. Farnesol and geranylgeraniol were also dose-dependent PPAR-\(\alpha\) activators in the PPAR-\(\alpha\) ligand assay system. In fact, they showed increases equal to 10 and 8.6 times compared to the vehicle controls, respectively [75]. These activities were as strong and nearly equal to 10 \(\upmu\)M fenofibrates, which were used as positive controls for PPAR-\(\alpha\). In this context, it seems that these farnesols and the geranylgeraniol isoprenols exert their effects through a dual stimulation of both PPAR-\(\gamma\) and PPAR-\(\alpha\)[76]. Two new oleanane-type triterpene saponins, tarasaponin IV and elatoside L, and four well-recognized ones, namely stipuleanoside R, kalopanax-saponin F, kalopanax-saponin F-methylester, and elatoside D, were extracted from _elatoside L_ and _kalopanax saponin F_ and found to suppress at a dose-dependent manner TNF-\(\alpha\)-stimulated NF-\(\kappa\)B activation compared to the positive control, sulfasalazine [77]. Both elatoside L and kalopanax saponin inhibited the expression of iNOS and COX-2 mRNA produced by TNF-\(\alpha\). In addition, kalopanax saponin F, kalopanax saponin F methyl ester, and elatoside D drastically enhanced the PPAR-\(\gamma\) expression. No other PPAR subtype was activated by the above compounds [77]. Two novel meroterpene analogues, chrysogenester and 5-farnesyl-2-methyl-1-O-methylhydroquinone, have recently been isolated by jellyfish fungus _Penicillium chrysogenum_ J08 NF-4 [78]. Four well-known farnesyl meroterpenes were also isolated [78]. The dock analysis of the chrysogen ester showed that it could bind to PPAR-\(\gamma\) in a similar manner to amorftutin B, a naturally occurring PPAR-\(\gamma\) ligand [78]. Chrysogenester induced the activation of PPAR-\(\gamma\) in mice Ac2F hepatic cells and enhanced the PPAR-\(\gamma\) protein amounts in mice RAW 264.7 macrophages. To investigate the potential anti-inflammatory properties of chrysogenester and the mechanisms involved, an in vitro study was also carried out [78]. In RAW 264.7 macrophages, chrysogenester suppressed the NF-\(\kappa\)B p65 subunit phosphorylation and reduced the levels of several pro-inflammation-related molecules such as iNOS, NO, COX-2, TNF-\(\alpha\), IL-18, and IL-6 [78]. Thus, chrysogenes may suppress the inflammatory response through the stimulation of PPAR-\(\gamma\) and the subsequent inhibition of the NF-\(\kappa\)B signaling pathway, thereby reducing the levels of the above pro-inflammation-related agents [78]. Auraptene is found in several citrus fruits and has been found to have anti-inflammatory and anticarcinogenic properties [79]. In adipocytes cultures, auraptene increased the antiatherogenic, antidiabetic, and anti-inflammatory cytokine, adiponectin, and decreased the pro-inflammatory cytokine, monocyte chemoattractant protein-1 (MCP-1) [80].