Pharmacological Approaches to Attenuate Inflammation and Obesity with Natural Products Formulations by Regulating the Associated Promoting Molecular Signaling Pathways

Abstract

Obesity is a public health problem characterized by increased body weight due to abnormal adipose tissue expansion. Bioactive compound consumption from the diet or intake of dietary supplements is one of the possible ways to control obesity. Natural products with adipogenesis-regulating potential act as obesity treatments. We evaluated the synergistic antiangiogenesis, antiadipogenic and antilipogenic efficacy of standardized rebaudioside A, sativoside, and theasaponin E1 formulations (RASE1) in vitro in human umbilical vein endothelial cells (HUVECs), 3T3-L1 preadipocytes respectively, and in vivo using a high-fat and carbohydrate diet-induced obesity mouse model. Orlistat was used as a positive control, while untreated cells and animals were normal controls (NCs). Adipose tissue, liver, and blood were analyzed after dissection. Extracted stevia compounds and green tea seed saponin E1 exhibited pronounced antiobesity effects when combined. RASE1 inhibited HUVEC proliferation and tube formation by suppressing VEGFR2, NF-κB, PIK3, and-catenin beta-1 expression levels. RASE1 inhibited 3T3-L1 adipocyte differentiation and lipid accumulation by downregulating adipogenesis- and lipogenesis-promoting genes. RASE1 oral administration reduced mouse body and body fat pad weight and blood cholesterol, TG, ALT, AST, glucose, insulin, and adipokine levels. RASE1 suppressed adipogenic and lipid metabolism gene expression in mouse adipose and liver tissues and enhanced AMP-activated protein kinase levels in liver and adipose tissues and in serum adiponectin. RASE1 suppressed the NF-κB pathway and proinflammatory cytokines IL-10, IL-6, and TNF-α levels in mice which involve inflammation and progression of obesity. The overall results indicate RASE1 is a potential therapeutic formulation and functional food for treating or preventing obesity and inflammation.

Dietary tea seed saponin combined with aerobic exercise attenuated lipid metabolism and oxidative stress in mice fed a high‐fat diet (HFD)

“…We also discovered that TSS + AE has a synergistic effect in promoting hepatic AMPK and SIRT1 and that TSS and TSS + AE have similar activity in modulating PGC‐1α protein levels in the liver of obese mice. Theasaponin E1 enhances AMPK phosphorylation and inhibits lipid synthesis in 3T3‐L1 preadipocytes (Khan et al, 2021). EGCG can activate hepatic AMPK activity, upregulate SIRT1 protein expression, promote lipolysis and FA oxidation, and reduce levels of TC, non‐esterified Fas, and LDL‐c in serum of the obese mice.…”

Current Evidence of Natural Products Against Overweight and Obesity: Molecular Targets and Mechanisms of Action

“…A rich in saponins fraction obtained from green tea seeds was used to design a formulation with glucosides extracted from Stevia rebaudiana (stevia) and evaluated in 3T3-L1 cells. The combination showed a synergic behavior and significantly inhibited the expression of adipogenesis and lipogenesis related genes and signaling molecules: PPARγ, C/EBPα, aP2, and SREBP-1c (sterol regulatory element-binding protein) [73].…”

Sulfated Glucan from the Green Seaweed Caulerpa sertularioides Inhibits Adipogenesis through Suppression of Adipogenic and Lipogenic Key Factors

“…Yet, the use of these drugs is associated with serious negative side effects, with gastrointestinal disturbances, oily stools, incontinence, and cases of pancreatitis being described [ 5 ]. Therefore, significant attention has been paid to natural compounds to develop new approaches to preventing and treating obesity and its related diseases [ 6 , 7 , 8 ].…”