Ergosterol Peroxide from the Medicinal Mushroom Ganoderma lucidum Inhibits Differentiation and Lipid Accumulation of 3T3-L1 Adipocytes

Abstract

Ergosterol peroxide is a natural compound of the steroid family found in many fungi, and it possesses antioxidant, anti-inflammatory, anticancer and antiviral activities. The anti-obesity activity of several edible and medicinal mushrooms has been reported, but the effect of mushroom-derived ergosterol peroxide on obesity has not been studied. Therefore, we analyzed the effect of ergosterol peroxide on the inhibition of triglyceride synthesis at protein and mRNA levels and differentiation of 3T3-L1 adipocytes. Ergosterol peroxide inhibited lipid droplet synthesis of differentiated 3T3-L1 cells, expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAT/enhancer-binding protein alpha (C/EBPα), the major transcription factors of differentiation, and also the expression of sterol regulatory element-binding protein-1c (SREBP-1c), which promotes the activity of PPARγ, resulting in inhibition of differentiation. It further inhibited the expression of fatty acid synthase (FAS), fatty acid translocase (FAT), and acetyl-coenzyme A carboxylase (ACC), which are lipogenic factors. In addition, it inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) involved in cell proliferation and activation of early differentiation transcription factors in the mitotic clonal expansion (MCE) stage. As a result, ergosterol peroxide significantly inhibited the synthesis of triglycerides and differentiation of 3T3-L1 cells, and is, therefore, a possibile prophylactic and therapeutic agent for obesity and related metabolic diseases.

Effects of different graphene‐based nanomaterials as elicitors on growth and ganoderic acid production by Ganoderma lucidum

“…28,29 G. lucidum is one of the most well-known medicinal mushrooms and has been used for its therapeutic effects for more than 2,000 years. [31][32][33][34] GAs are the most significant secondary metabolites of G. lucidum and have many potential therapeutic applications, as claimed by numerous literature. 35,36 There is a considerable amount of researches that describes the influence of different parameters on growth and GA production of G. lucidum, such as optimization of fermentation conditions, elicitation, and molecular biology technique to achieve higher expression of GA biosynthesis-related genes.…”

“…In the last two decades, numerous studies have explored the active components of G. lucidum and their biological effects along with underlying mechanisms of action 30 . To date, over 300 active compounds have been isolated from G. lucidum with numerous biological activities, including anti‐inflammatory, immune regulation, anti‐tumor, hepatoprotective, hypoglycemic, anti‐aging, neuroprotection, and antioxidant activities 31‐34 . GAs are the most significant secondary metabolites of G. lucidum and have many potential therapeutic applications, as claimed by numerous literature 35,36 .…”

Implementation of food safety management systems that meets ISO 22000:2018 and HACCP: A case study of capsule biotechnology products of chaga mushroom

“…The functional properties of edible mushrooms have received much attention. For instance, Ganoderma lucidum is used in the prevention and treatment of obesity and other metabolic diseases (Jeong & Park, 2020); Agaricus blazei has been demonstrated to have antitumor, anti‐inflammatory, and antiallergic effects (Hetland et al., 2020); and Trametes versicolor was shown to exhibit AChE inhibitory activity as well as tumor cell cytotoxic activity (Janjušević et al., 2017; 2018). The diversity of functional and appealing product properties offered by biotechnology products have grown over the years, and among them, the chaga mushroom ( Inonotus obliquus ) is a product that has been shown by several studies to contain biologically active ingredients, such as polysaccharides, triterpenoids, steroids, phenolic compounds, and melanin complexes (Chen, Chen, Liu, Liou, & Chen, 2020; Huang, Ding, & Fan, 2012; Kukulyanskaya, Kurchenko, Kurchenko, & Babitskaya, 2002; Liu et al., 2014; Nakajima, Sato, & Konishi, 2007; Wang et al., 2014; Zheng et al., 2011), earning it a reputation as the “King of Immune‐Boosting Foods and the Diamond of the Forest.” In terms of health benefits, the chaga mushroom contains antioxidants capable of scavenging free radicals, and possesses blood sugar reducing, antiviral, anti‐inflammatory, blood lipid reducing, blood pressure alleviating, immunomodulatory, and anticancer properties (Chen, Liu et al., 2020; Chen, Xu, & Zhu 2010; Choi et al., 2010; Kim et al., 2005; Patel & Goyal 2012; Song, Liu, Kong, Chang, & Song, 2013; Sun et al., 2008; Zheng, Zhang, Zhao, Miao, & Jiang, 2009), while not causing any unacceptable side effects (Chen, Chen, Liu, Liou, & Chen, 2019; Hou & Wei, 2008; Song et al., 2008).…”

Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies

“…Ergosterol peroxide (5α,8α-epidioxiergosta-6,22-dien-3β-ol, EP) is a member of a class of fungal secondary metaboliters of sterol 5α,8α-endoperoxidederivatives ( Figure 2). A number of biological activities have been attributed to EP, including antitumor, anti-inflammatory, antiviral and immunomodulatory activities and antioxidant activities [16][17][18][19][20][21]. As an important active lead compound in drug discovery, EP is well known for its 5α,8α-peroxy moiety.…”