## 3 Effect of PS on Components of MetS
### Effect of PS on Obesity  
Obesity is a major risk factor for developing MetS. Central obesity occurs when the excess energy in the body is stored in adipocytes, causing them to undergo hypertrophy [38]. The hypertrophic adipocytes actively secrete proinflammatory cytokines, such as IL-1, IL-6, and TNF-\(\alpha\), resulting in low-grade chronic systemic inflammation [39; 40]. Inadequate blood supply of the expanded adipose tissue results in cellular hypoxia and necrosis. Inflammation infiltration at the necrotic sites and the removal of cellular debris through phagocytosis could increase oxidative stress due to the release of free radicals such as NO and H\({}_{2}\)O\({}_{2}\)[41; 42], which further exacerbates the metabolic derangements [43]. Obesity is also associated with increased levels of the highly reactive advanced glycation and lipoxidation end-products [44; 45], which support the development of other MetS components. Weight loss interventions, such as lifestyle, dietary, pharmacological, and surgical interventions, are frequently prescribed to MetS patients [12; 46]. PS has been reported to reduce visceral fat in vivo [47]. Visceral fat is a hormonally active component of total body fat with distinct biochemical properties that influence various physiological and pathological processes in the human body [48]. Medical conditions such as metabolic syndrome and cardiovascular disease have been linked to abnormally high visceral fat deposition [48]. Chronic glucocorticoid therapy causes weight gain and visceral adiposity [49]. Excess glucocorticoids can cause a rise in circulating free fatty acids, lipid build-up in skeletal muscle and the liver, and adipocyte differentiation and  
Figure 1: PRISMA flow chart for the literature search. size, thereby increasing visceral adiposity [50]. In a study by [PERSON] et al. [47], PS aqueous extract (125 mg/kg/day for 48 days) reduced visceral fat deposition and the diameter of an adipocyte membrane in adrenalectomized male Sprague Dawley rats with obesity induced by dexamethasone. This suggests that PS might reduce lipid content in adipose tissues as the thickening of the adipocyte membrane is associated with an increased lipid content of adipose tissue [51]. However, the area, perimeter, and width of the individual perirenal adipocytes were not significantly different between the PS-treated and untreated groups. These findings suggested that it did not suppress adipocyte hypertrophy [47]. 11\(\beta\)-hydroxysteroid dehydrogenase type 1 (11\(\beta\)HSD-1) is an enzyme that catalyses the conversion of 11-dehydrocorticosterone to corticosterone and vice versa, leading to hypertrophy and hyperplasia of adipocytes [47] and decreased adiponectin levels [52]. 11\(\beta\)HSD-1 activity has been reported to be increased in animal models of obesity and the subcutaneous adipose tissue of obese human subjects [53]. Adiponectin is an adipocyte-derived hormone negatively regulated by visceral fat accumulation [54]. Even though adiponectin is secreted by fat cells, obese people have significantly lower levels of adiponectin than non-obese people [55; 56; 57]. Women are reported to have higher plasma adiponectin levels than men, despite having a higher body fat percentage. According to [PERSON] et al. [58], plasma adiponectin levels in women are 65% higher than in men, especially in relatively lean individuals. This sex difference in adiponectin levels has been confirmed by other studies [56; 59]. Moreover, overexpression of 11\(\beta\)HSD-1 has been reported to increase leptin levels [60; 61]. Leptin is a hormone secreted by adipocytes that reduces food intake and regulates body fat by increasing energy expenditure [62]. Leptin increases with adiposity [63; 64], as evidenced by obese rodents and humans having higher levels of circulating leptin. These observations suggest the development of leptin resistance [64; 65]. Leptin resistance promotes hunger and increases food intake, resulting in weight gain [66].