## 3 Results
Ferulic acid and fish oil were shown to have anti-inflammation and renal-protective properties that were ascribed to their capability to activate PPAR-\(\gamma\). Given that ferulic acid and fish oil are naturally occurring agents, they could be considered as less dangerous alternatives when exposed to nephrotoxins [92]. _Conocarpus lancifolius_ (Combretaceae), a Saudi Arabian medicinal plant, was found to have potent antidiabetic activity, and its fruit extract has been shown to have cytotoxic effects against MRC-5 cancer cells, as well as notable antimicrobial action [93]. In this regard, a study assessed the anti-inflammation, cytotoxicity, PPAR, and antioxidant properties of _C. lancifolius_ plant extracts and their pure isolated components [93]. A novel trimethoxylelike acid derivative and two molecules, kaempfer-3-O-rutinoside and beta-sitosterolglucoside 3, were extracted from _Conocarpus lancifolius_. Kaempfer 3-O-rutinoside was found to activate both PPAR-\(\alpha\) and PPAR-\(\gamma\) with a 2.6-times increase in the PPAR-\(\alpha\) activity and a 2.2-times increase in the PPAR-\(\gamma\) activity [93]. This was the initial study that isolated and screened the potential pharmacological properties of the extracts and pure compounds from _C. lancifolius_ fruits, which were associated with PPAR-\(\alpha\) and PPAR-\(\gamma\) activity [93]. A 4D label-free quantitative proteomics and network pharmacological survey assessed the molecular action of a _Fructus alpiniae zerumbet_ essential oil on the vascular endothelium cellular senescence in diabetes [94]. In this study, mice with diabetes receiving a high fat and high glucose diet in combination with an intraperitoneal infusion of a low dosage of streptozotocin (STZ, 30 mg/kg) and an oral administration of _Fructus alpiniae zerumbet_ essential oil were used [94]. A model of human aortic endothelium cellular senescence treated with high palmitic acid and high glucose concentrations in vitro was also used. Treatment with _Fructus alpiniae zerumbet_ essential oil improved the aberrant lipids' metabolic process, the pathological tissue impairment to the vessels, as well as the ageing of the vascular endothelium in diabetic mice [94]. The proteomics and network pharmacological analysis confirmed the different proteins' expressions and the potential drug targets, which were related to the PPAR-\(\gamma\) signaling pathway. In addition, the molecular dock analysis showed that certain small molecules derived by _Fructus alpiniae zerumbet_ essential oil had an enhanced PPAR-\(\gamma\) affinity [94]. Thus, the _Fructus alpiniae zerumbet_ essential oil improved the vascular endothelium cellular senescence in diabetic mice by activating the PPAR-\(\gamma\) signaling, highlighting the possible advantageous pharmacological properties of _Fructus alpiniae zerumbet_ essential oil and providing a rationale for its clinical implementation in diabetic endothelium cellular senescence [94]. The objective of another study was to explore a novel naturally occurring PPAR-\(\gamma\) ligand with fewer side effects compared to rosiglitazone in db/db mouse animals [95]. A PPAR-\(\gamma\) ligand, 18:0 lysophosphatidylcholine, was identified using an in-house natural products' database with a virtual screening methodology. Further, 18:0 Lysophosphatidylcholine showed similar hypoglycemic efficacy to rosiglitazone via PPAR-\(\gamma\) activation. It had significantly lower side effects compared to rosiglitazone [95]. Notably, 18:0 lysophosphatidylcholine reduced liver injury and cardiotoxicity in db/db mouse animals. A decrease in fatty acid biosynthesis, facilitated by the stimulation of the phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase-alpha (AMPK\(\alpha\)) and acetyl-CoA carboxylase (ACC), and an enhancement in the expression of UCP1 and PPAR-\(\gamma\) coactivator-1 alpha (PGC1-\(\alpha\)), may be the potential mechanisms by which this naturally occurring molecule can attenuate the symptoms of metabolic syndrome [96].