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  • IOX2 Introduction Psoralea corylifolia L Leguminosae

    2020-05-21

    Introduction Psoralea corylifolia L. (Leguminosae) is a well-known traditional Chinese medicine, and it has been widely used for the treatment of various diseases like bronchial asthma, leucopenia, vitiligo and psoriasis in East Asian countries (Zhang et al., 1990). Previous studies have reported that the major metabolites of P. corylifolia are coumarins, flavonoids, and meroterpenoids of the monoterpene phenol class (Haraguchi et al., 2002; Wang et al., 2001; Cho et al., 2001). In addition, these chemical constituents exhibited several therapeutic activities including antioxidant activities, stimulate osteoblast proliferation and hepatoprotective effect. Recent pharmacological and clinical studies showed that extract of P. corylifolia possess diverse bioactivities, such as antidermatophytic, antihyperglycemic, antiplatelet and antitumor activities (Tsai et al., 1996; Krenisky et al., 1999; Latha et al., 2000). Published article showed that the ethanol extract of Psoralen seed exhibit antihyperglycemic and antioxidative effects on the type 2 diabetes (Kamboj et al., 2011). Therefore, we explored more bioactive compounds of P. corylifolia to conduct a more in-depth study of Psoralen seed, and provide lead compounds for future treatment with diabetes. Triacylglycerol (TG) is a kind of fat molecule which participate in the physiological metabolism. Excess TG accumulation would result in obesity and related diseases. So inhibiting TG synthesis may ameliorate obesity and its related medical consequences. DGAT is a key enzyme in TG synthesis and catalyzes the final step of the TG synthesis pathway by using diacylglycerol and fatty acyl CoA as substrates (Kim et al., 2013). DGAT1 and DGAT2 are two forms of DGAT, which have been identified and both enzymes are ubiquitously expressed especially in white adipose tissue, small intestine and liver (Turchetto-Zolet et al., 2011). However, only DGAT1 is regarded as a key enzyme that responsible for synthesis of TG. Thus, DGAT1 may be an important target to alter the IOX2 equation. As a part of our research on seeking active compounds of inhibiting DGAT from the seed of P. corylifolia, we reported the isolation and structure elucidation of eleven flavonoid derivatives, of which 1–4 were new compounds, 9 was isolated from this plant for the first time. Their DGAT inhibitory activities were evaluated separately.
    Experimental
    Acknowledgements This research was financially supported by the Scientific and Technological Developing Scheme of Jilin Province of People’s Republic of China (20150101225JC).
    Introduction Modern lifestyle is marked by increased caloric intake, decreased mobility, and a paradoxical demand for slimmer body silhouettes. Data collected from 199 countries between 1980 and 2008 suggest a steadily increasing prevalence of obesity in every region of the world [1]. The World Health Organization has estimated the number of overweight persons to be 1.9 billion adults as of 2016, increased 0.5 billion (35% rise) since 2014, and about 650 million of these were categorized as obese, which is 50 million more than the number of obese adults in 2014 (8.3% rise) [2]. Given the health burden, there has been a sustained interest in the enzymes contributing to triacylglycerol (TAG) synthesis. Excessive accumulation of TAGs in adipose and non-adipose tissues is a hallmark of obesity and the ancillary problem of metabolic syndrome characterized by a cluster of metabolic disarrangement such as insulin resistance, type 2 diabetes, hypertension, dyslipidemia, cardiovascular disease, and non-alcoholic fatty liver disease [[3], [4], [5]]. Reduced lipid storage in obese adipose tissue limits the capacity of the subcutaneous adipose tissue to act as a protective metabolic sink for the clearance and storage of the extra energy derived from the diet [6]. This exposes cells to the toxic impact of the excess lipids [7]. At the cellular level, a widening waistline is a result of lipid accumulation in adipose tissue, and the morbidities are linked to ectopic lipid accumulation in non-adipose tissues such as liver, skeletal muscle, and pancreas [8]. The accumulated lipids are largely TAG sequestered into lipid droplets (LDs) stored in the cytoplasm in adipose and non-adipose tissues [9]. TAG is synthesised de novo by sequential addition of fatty acyl moieties to a glycerol-3-phosphate (G3P) backbone (the G3P pathway, also known as the Kennedy pathway as it was originally described by Kennedy et al. in 1956) [10], the re-esterification of hydrolysed TAG, diacylglycerol (DAG) and monoacylglycerol (MAG) (the re-esterification of partial glycerides pathway), and the MAG pathway in the endoplasmic reticulum (ER) membrane [11,12] (Fig. 1). In the liver, the TAGs are mainly synthesized de novo by the G3P pathway and by re-esterification of DAG and MAG, and the synthesised TAGs are largely packed into very low-density lipoproteins (VLDLs) in the lumen of the ER. The VLDLs are then transported in the membrane-bound VLDL transport vesicles across the Golgi apparatus to the plasma membrane and secreted into the circulatory system [13] (Fig. 1). In adipose tissue, the de novo synthesized TAGs or TAGs derived from the re-esterification of DAG are stored as LDs in the cytoplasm as energy reserves [14,15]. In the small intestine, dietary TAGs are broken down to fatty acids (FAs) and MAGs that are then re-synthesized into new TAGs using the MAG pathway. The new TAGs are packed as chylomicrons and secreted into the circulatory system [15].