br Introduction The traditional Chinese medicine TCM Ganoder

Introduction The traditional Chinese medicine (TCM), Ganoderma (G.) lucidum Karst is a well-known mushroom which has been used clinically in some Asian countries. It is termed “Lingzhi” in China, “Reishi” in Japan and “Yeongji” in Korea. It has long been used in TCM for the promotion of longevity and maintenance of vitality [1]. Modern chemical researches on G. lucidum have revealed a wide array of bioactive metabolites, such as polysaccharides, triterpenoids, meroterpenoids and sterols, alkaloids [2]. Bioactivity studies has shown that G. lucidum possess various biological properties, such as antihypertensive, anticancer, antiviral and immunomodulatory activities [3], [4], [5], [6]. Metabolic syndrome characterized by insulin resistance, central obesity, elevated blood pressure and dyslipidemia have become a worldwide public health issue [7], [8]. The current clinical drugs for the treatment of diabetes and metabolic syndrome (e.g. insulin, statins, fibrates and angiotensin-converting enzyme inhibitors) are still facing some problems due to the limitation of the therapeutic efficacy and the accompanying side effects. Considerable efforts have been made to develop a new drug that can ameliorate the metabolism of both 103 9 and lipids without side effects in the pharmaceutical industry. HMG-CoA reductase, aldose reductase and α-glucosidase are targets of various drugs to treat metabolic syndrome. In our continuous researches on bioactive components from Ganoderma species, some meroterpenoids and triterpenoids showed strong inhibitory activities against HMG-CoA reductase, aldose reductase or α-glucosidase activity [5], [9]. In an early report, an in silico screening method was used to predict the interaction of Ganoderma constituents with the targets involved in the metabolic syndrome [10]. A number of triptepenes from G. lucidum were disclosed as putative bioactive agents for the treatment of metabolic syndrome. To confirm the hypoglycemic and hypolipidemic bioactivities of Ganoderma tripterpenes in vitro, we conducted chemically investigated on the fruiting bodies of G. lucidum collected from Sichuan and Fujian Province of China. As a result, 73 known compounds (Fig. 2 & Table 1) and 7 new compounds (Fig. 1) including four lanostane triterpenes (1–4) and three triterpene-farnesyl hydroquinone conjugates (5–7) were obtained. And one farnesyl hydroquinone (8) (Fig. 1) was first reported as a natural product. Bioactivities of 81 compounds were tested against HMG-CoA reductase, aldose reductase (AR), α-glucosidase, and protein tyrosine phosphatase 1B (PTP1B). Herein, we reported the isolation, structural determination, and bioactivities of compounds isolated from the fruiting bodies of G. lucidum.
Experimental
Acknowledgements Financial supports of the National Natural Science Foundation of China (21472233 and 81673334), the Ministry of Science and Technology of the People’s Republic of China (2014CB138304), the Youth Innovation Promotion Association of Chinese Academy of Sciences (2014074) are acknowledged. Dr. Jinwei Ren and Dr. Wenzhao Wang (State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences) are appreciated for their help in measuring the NMR and MS data.
Introduction Diabetes mellitus (DM) is a prevalent metabolic disease globally affecting almost 366 million individuals and the number is predicted to increase up to 552 million by the year 2030 [1]. Diabetic patients have high level of blood glucose that results in structural and functional changes in various tissues like retina, kidney and peripheral nerves, hence leading to long term complications [2]. Aldose reductase (ALR2; EC 1.1.1.21) belongs to the aldo-keto superfamily. ALR2 is the first and rate-limiting enzyme involved in polyol pathway which, utilizing NADPH asa co-factor, converts glucose into sorbitol [3]. Sorbitol dehydrogenase further converts sorbitol into fructose using NAD+ asa co-factor [4], [5], [6]. Under normal physiological balance, glucose is metabolized in the liver by glycolytic pathway for energy utilization, in this condition ALR2 plays a minor role in glucose metabolism [4], [5]. However, the role of ALR2 is significantly enhanced during hyperglycemic condition and it converts excess glucose to sorbitol in insulin independent tissues like nerve, lens, retina and kidney [7]. This excess amount of sorbitol cannot pass through the cell membrane and results in osmotic stress, which finally leads to innumerable tissue-based pathologies associated with the long-term diabetic disorders including cataract formation, nephropathy, retinopathy and neuropathy [8], [9], [10].