Abstract
Hispidulin is abundant in Arrabidaea chica, Crossostephium chinense, and Grindelia argentina, among others. p-Synephrine is the main phytochemical constituent of Citrus aurantium. It has been used in combination with various other phytochemicals to determine synergistic effects in studies involving human participants. However, there have been no reports comparing the anti-adipogenic effects of the combination of hispidulin and p-synephrine. The current study explores the anti-adipogenic effects of hispidulin alone and in combination with p-synephrine in a murine preadipocyte cell line, 3T3-L1. Co-treatment resulted in a greater inhibition of the formation of red-labeled lipid droplets than the hispidulin or p-synephrine-alone treatments. Co-treatment with hispidulin and p-synephrine also significantly inhibited adipogenic marker proteins, including Akt, mitogen-activated protein kinases, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, glucocorticoid receptor, and CCAAT/enhancer-binding protein β. Although further studies are required to assess the effects of each drug on pharmacokinetic parameters, a combination treatment with hispidulin and p-synephrine may be a potential alternative strategy for developing novel anti-obesity drugs.
Highlights
IntroductionIn the development of obesity, an increased adipose tissue size results in an increased adipocyte cell size (adipocyte hypertrophy) and adipocyte cell number (adipocyte hyperplasia) [2]
Adipogenesis is a process by which preadipocytes differentiate into mature adipocytes [1].In the development of obesity, an increased adipose tissue size results in an increased adipocyte cell size and adipocyte cell number [2]
AKT1, SRC, EGFR, and GSK3B were identified as key anti-obesity target genes of hispidulin, and estrogen, prolactin, Rap1, and PI3K-Akt signaling pathways were predicted to be involved in the anti-obesity effects of hispidulin
Summary
In the development of obesity, an increased adipose tissue size results in an increased adipocyte cell size (adipocyte hypertrophy) and adipocyte cell number (adipocyte hyperplasia) [2]. These mechanisms are implicated in childhood obesity and obesity-related metabolic disturbances [3]. The use of these drugs is limited due to critical side effects, such as dizziness, dry mouth, anxiety, insomnia, and increased blood pressure [11]. For these reasons, several studies have attempted to find safe phytochemicals
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