Zanthoxylum schinifolium leaf ethanol extract inhibits adipocyte differentiation through inactivation of the extracellular signal regulated kinase and phosphoinositide 3-kinase/Akt signaling pathways in 3T3-L1 pre-adipocytes

Abstract

Zanthoxylum schinifolium is widely used as a food flavoring in east Asia. Although this plant has also been used in traditional oriental medicine for the treatment of the common cold, toothache, stomach ache, diarrhea and jaundice, its anti-obesity activity remains to be elucidated. The present study investigated the effects of ethanol extract from the leaves of Z. schinifolium (EEZS) on adipocyte differentiation, and its underlying mechanism, in 3T3-L1 pre-adipocytes. The results demonstrated that EEZS effectively suppressed intracellular lipid accumulation at non-toxic concentrations, and was associated with the downregulation of several adipocyte-specific transcription factors, including peroxisome proliferation-activity receptor γ (PPARγ), CCAAT/enhancer binding protein (C/EBP)α and C/EBPβ, in a concentration-dependent manner. Furthermore, it was observed that EEZS markedly inactivated the extracellular signal-regulated protein kinase (ERK) and phosphatidylinositide 3-kinase (PI3K)/Akt pathways, which act upstream of PPARγ and C/EBPs in adipogenesis. These results suggested that EEZS inhibited lipid accumulation by downregulating the major transcription factors involved in the pathway of adipogenesis, including PPARγ, C/EBPα and C/EBPβ, via regulation of the ERK and PI3K/Akt signaling pathways in 3T3-L1 adipocyte differentiation. This indicated the potential use of EEZS as an anti-obesity agent.

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“…PI3K/Akt pathway has different function between different adipocytes. In human adipocytes, PI3K/Akt pathway can promote the proliferation and differentiation [ 35 ], while, PI3K/Akt pathway can inhibit the proliferation and differentiation in 3T3-L1 [ 36 ]. In our study, PI3K/Akt pathway was enriched.…”

Aged green tea reduces high-fat diet-induced fat accumulation and inflammation via activating the AMP-activated protein kinase signaling pathway

“…The commonly prescribed weight-loss drugs like orlistat, sibutramine, and rimonabant cause side effects, such as oily stools and flatulence (30). Several studies have identified plant-derived bioactive compounds with significant anti-obesity and weight-loss effects (31)(32)(33)(34). For instance, tea brewed from fresh leaves of C. sinensis has several beneficial effects.…”

Induction of apoptotic cell death in human bladder cancer cells by ethanol extract of Zanthoxylum schinifolium leaf, through ROS-dependent inactivation of the PI3K/Akt signaling pathway

“…EEZS was extracted as described previously [ 19 ]. Briefly, 80 g finely powdered dried leaves of Z. schinifolium were soaked in 1,500 mL 100% ethanol for 48 h. The liquid extract was then filtered using filter paper (Whatman No.…”

“…Z. schinifolium is also prescribed as a herbal medicine in traditional practice to treat several symptoms [ 14 15 16 ]. To corroborate these applications, a number of pharmacological activities of the plant have been reported, which include anti-viral, anti-obesity, antioxidant, immunostimulatory, and anti-inflammatory effects [ 15 17 18 19 20 21 22 23 ]. Although recent studies show that Z. schinifolium exerts antitumor effects on human cancer cells [ 24 25 26 27 ], the underlying mechanisms have not been clearly elucidated.…”