No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Exposure assessment of lovastatin in Pu-erh tea
Abstract
This paper reports the results of an extensive survey on the levels of lovastatin in Pu-erh tea samples. The microbial source of lovastatin was assessed by testing the ability of fungi with higher isolation frequency in the Pu-erh tea samples to produce lovastatin on Czapek yeast extract agar (CYA). Lovastatin was not detected in any of the raw Pu-erh tea samples without storage but was found in almost all the ripe Pu-erh tea samples, with lovastatin contents ranging from 20.61ng/gdw to 226.38ng/gdw. After five years' storage, the lovastatin levels increased obviously in ripe Pu-erh tea samples and 55% of raw Pu-erh tea samples from 2007 were found to contain lovastatin with concentrations ranging between 28.41ng/gdw and 228.61ng/gdw. With increasing storage time, lovastatin concentration in ripe Pu-erh tea, and the occurrence and concentration of lovastatin for raw Pu-erh tea increased significantly. Three genera of fungi: Aspergillus, Penicillium and Trichoderma were often isolated from Pu-erh tea samples. A total of 40 strains from 3 fungal genera were selected to test their ability to produce lovastatin. Only 6 strains, Aspergillus tubingensis, Aspergillus wentii, Aspergillus fumigatus, Penicillium chrysogenum, Trichoderma asperellum and Trichoderma citrinoviride, were able to produce lovastatin reaching concentrations of 9.59±0.42ng/g CYA, 2.33±0.21ng/g CYA, 2.77±0.13ng/g CYA, 3.36±0.69ng/g CYA, 4.8±0.17ng/g CYA, and 1.47±0.36ng/g CYA respectively in Czapek yeast extract agar.
... As a world-recognized, low-grade eukaryote with edible safety, Aspergillus niger is the dominant flora of Aspergillus, occupying 70-80% of Aspergillus and can thrive at 50 • C . Aspergillus fumigatus and Aspergillus tubingensis are also important components of Aspergillus, which can produce lovastatin that lowers cholesterol (Zhao et al., 2013). In addition, Penicillium belongs to the subphylum Deuteromycetes, which is able to produce a variety of enzymes and organic acids. ...
... In addition, Penicillium belongs to the subphylum Deuteromycetes, which is able to produce a variety of enzymes and organic acids. Its metabolite penicillin can inhibit the growth of miscellaneous bacteria and spoilage bacteria to a certain extent (Zhao et al., 2013). ...
Pu‐erh tea belongs to dark tea among six major teas in China. As an important kind of post‐fermented tea with complex microbial composition, Pu‐erh tea is highly praised by many consumers owing to its unique and rich flavor and taste. In recent years, Pu‐erh tea has exhibited various physiological activities to prevent and treat metabolic diseases. This review focuses on the fungi in Pu‐erh tea and introduces the sources, types, and functions of fungi in Pu‐erh tea, as well as the influence on the quality of Pu‐erh tea and potential safety risks. During the process of fermentation and aging of Pu‐erh tea, fungi contribute to complex chemical changes in bioactive components of tea. Therefore, we examine the important role that fungi play in the quality formation of Pu‐erh tea. The associations among the microbial composition, chemicals excreted, and potential food hazards are discussed during the pile‐fermentation of Pu‐erh tea. The quality of Pu‐erh tea has exhibited profound changes during the process of pile‐fermentation, including color, aroma, taste, and the bottom of the leaves, which are inseparable from the fungus in the pile‐fermentation of Pu‐erh tea. Specifically, the application prospects of various detection methods of mycotoxins in assessing the safety of Pu‐erh tea are proposed. This review aims to fully understand the importance of fungi in the production of Pu‐erh tea and further provides new insights into subtly regulating the piling process to improve the nutritional properties and guarantee the safety of Pu‐erh tea.
... Pu-erh tea also known as dark tea is produced in Yunnan, China. It is a traditional raw fermented tea, produced by microbial fermentation of freshly picked leaves of C. sinensis through two processes: the traditional raw fermented process and the speedier, ripened fermented process (Zhao et al. 2013). The post-fermentation stage is the most susceptible to mold invasion, and the pu-erh tea mycoflora deserves special attention. ...
... The post-fermentation stage is the most susceptible to mold invasion, and the pu-erh tea mycoflora deserves special attention. Fungal species such as Aspergillus, Blastobotrytis, Penicillium, Rhizopus, and Mucor have been found associated with pu-erh tea during fermentation process (Mogensen et al. 2009;Abe et al. 2008;Zhao et al. 2013;Zhao, Hu, and Liu 2015b). The study of Zhang et al. (2016a) reported A. niger, A. penicilloides, and A. cibarius were the major molds contaminating 85% of ripe and 60% of raw pu-erh tea out of 60 samples studied. ...
Tea (Camellia sinensis L.) is a high valued beverage worldwide since ancient times; more than three billion cups of tea are consumed each day. Leaf extracts of the plant are used for food preservation, cosmetics, and medicinal purposes. Nevertheless, tea contaminated with mycotoxins poses a serious health threat to humans. Mycotoxin production by tea fungi is induced by a variety of factors,
including poor processing methods and environmental factors such as high temperature and humidity. This review summarizes the studies published to date on mycotoxin prevalence, toxicity, the effects of climate change on mycotoxin production, and the methods used to detect and decontaminate tea mycotoxins. While many investigations in this domain have been carried out on the prevalence of aflatoxins and ochratoxins in black, green, pu-erh, and herbal teas, much less information is available on zearalenone, fumonisins, and Alternaria toxins. Mycotoxins in teas were detected using several methods; the most commonly used being the High-Performance Liquid Chromatography (HPLC) with fluorescence detection, followed by HPLC with tandem mass spectrometry, gas chromatography and enzyme-linked immunosorbent assay. Further, mycotoxins
decontamination methods for teas included physical, chemical, and biological methods, with physical methods being most prevalent. Finally, research gaps and future directions have also been discussed.
... Pu-erh tea is a unique Chinese tea, made from leaves from mature wild Bbroad leaf tea^trees, Camellia sinensis (L.) O. Kuntze var. assamica Kitamura, a tea variety from the Yunnan Province in China (Zhao et al. 2013), and can be classified into raw pu-erh tea (green tea like) and ripened pu-erh tea (post-fermented tea) according to processing procedures (Lee et al. 2013;Lv et al. 2014a). Generally, raw pu-erh tea will be considered ripened tea after having been naturally aged for several years. ...
... Generally, raw pu-erh tea will be considered ripened tea after having been naturally aged for several years. Ripened pu-erh tea is different from other teas for its fermentation (Zhao et al. 2013). Numerous socio-linguistic group in Yunnan Province, including the Bulang (Blang), Wa, Akha (Hani), Lahu, Yao, Hmong (Miao), Jinuo, De'ang, Dai and Han, have produced pu-erh tea for centuries (Gong et al. 2012). ...
A simple and efficient fingerprint analysis method was developed and validated for the quality consistency control and authentication of Deepure instant pu-erh tea within different manufacturers using high-performance liquid chromatography (HPLC) coupled with chemometrics. To compare the HPLC fingerprint chromatograms between batches, varieties and manufacturers, the correlation coefficients of similarities of 60 samples and the relative peak areas of 11 characteristic compounds were calculated. Different pattern recognition procedures, including hierarchical cluster analysis, principal component analysis and partial least squares discriminant analysis, were then applied to classify the instant pu-erh tea samples according to their variety and manufacturer. Results showed that the developed method has potential application for the quality consistency evaluation and discrimination of instant pu-erh tea samples from similar products.
... The water extract content of tea was measured according to the Chinese standard (GB/T 8305-2013 [24]); the tea polyphenol content was identified by the Folin-Ciocalteu method (GB/T 8313-2018 [25]); the free amino acid was assessed by the ninhydrin col-Nutrients 2024, 16, 998 3 of 18 orimetry method (GB/T 8314-2013 [25]); and total soluble sugars were detected by the anthrone-sulfuric acid colorimetric method [26]; determination of flavonoids by the method of aluminum trichloride [26]; theaflavins, thearubigins, and theabrownins were measured with the People's Republic of China Agricultural Industry Standard (NY/T 3675-2020 [27]). ...
Black tea (BT), the most consumed tea worldwide, can alleviate hyperlipidemia which is a serious threat to human health. However, the quality of summer BT is poor. It was improved by microbial fermentation in a previous study, but whether it affects hypolipidemic activity is unknown. Therefore, we compared the hypolipidemic activity of BT and microbially fermented black tea (EFT). The results demonstrated that BT inhibited weight gain and improved lipid and total bile acid (TBA) levels, and microbial fermentation reinforced this activity. Mechanistically, both BT and EFT mediate bile acid circulation to relieve hyperlipidemia. In addition, BT and EFT improve dyslipidemia by modifying the gut microbiota. Specifically, the increase in Lactobacillus johnsonii by BT, and the increase in Mucispirillum and Colidextribacter by EFT may also be potential causes for alleviation of hyperlipidemia. In summary, we demonstrated that microbial fermentation strengthened the hypolipidemic activity of BT and increased the added value of BT.
... In vitro demonstration of the presence of lovastatin in ripe Pu-Erh tea leaves, and increased levels after five years of storage which may be attributable to growth of fungal populations (Aspergillus, Penicillium and Trichoderma genera) [46] Bacopa/ Brahmi ...
... These studies did not take in to account the possible contribution of natural sources of lovastatin-like (monacholin K) compound present in food and drinks, e.g. pu-erh tea [62], oyster mushroom [63] and red yeast rice [64]. It is unclear whether age plays a role in the pathogenesis of anti-HMGCR myopathy; 92.3% (n = 24/26) of the subgroup of patients aged ≥ 50 years had exposure to statin before [58]. ...
Purpose of Review
We describe and discuss the safety of statins and non-statin drugs in neuromuscular disorders (NMDs). We also propose a pragmatic model of care for the management of such cases.
Recent Findings
Patients with both NMD and hypercholesterolemia may be particularly disadvantaged owing to the toxic effects of cholesterol-lowering therapy and the inability to take medication. Specifically, the management of hypercholesterolemia in patients with NMD is complicated by the increased risk of statin-related myotoxicity and concerns that statins may aggravate or possibly induce the onset of a specific NMD. The most severe form of statin-related myotoxicity is immune-mediated necrotizing myopathy.
Summary
Management of hypercholesterolemia in patients with NMDs include treating modifiable factors, consideration of toxicity risk of statin, use of non-statin lipid lowering agents, noting possible drug interactions, and careful monitoring.
... This drug inhibits the enzyme hydroxyl methylglutaryl CoA (HMG-CoA reductase) to limit cholesterol production. [1] Recent research has found that Lov demonstrated the ability to kill tumor cells by suppressing the genes involved in cell division, increasing the activity of cell cycle inhibitors, [2,3] to inhibit the growth of human acute myeloid leukemia (AML) cells [4] and the metabolism of breast cancer cells. [5] However, the Lov which is mainly absorbed in the gastrointestinal tract is poorly soluble in water (4.10 -3 mg/mL) [6] leading to its low bioavailability. ...
The chitosan/carrageenan/lovastatin biomaterials were prepared using a solution technique with 5 % lovastatin and a variable chitosan/carrageenan mass ratio. Fourier transform infrared spectroscopy (FT-IR) and field emission scanning electron microscopy (FESEM) images revealed that the complex's components were well dispersed into each other without changing the chemical structure, forming dipole interactions and hydrogen bonds among them. The abilities to release Lovastatin (Lov) in pH 2 and pH 7.4 solutions, corresponding to the environments in stomach and intestinal fluids, respectively, are both affected by the ratio of polymer components. The best results were obtained with the chitosan/carrageenan/lovastatin (w/w/%w = 10/90/5%) (CsCL195) biomaterial sample in which the particles are evenly dispersed. While the drug release process was poor in the pH 2 solution (gastric juice), a good release observed in the pH 7.4 solution (intestinal fluid) allows facilitating drug absorption through the intestinal mucosa cells into the blood, from which the effects of hypercholesterolemia treatment can be obtained.
... The first FDA-approved secondary metabolite was Lovastatin, to lower cholesterol levels. In oyster mushrooms [42], red yeast rice [43], and Pu-erh [44], Lovastatin occurs naturally in low concentrations. Their mode of action is inhibition of HMG-CoA reductase, and it is the enzyme responsible for converting HMG-CoA to mevalonate. ...
Natural products are substances that are confined from living organisms, they are in the form of primary or secondary metabolites. Secondary metabolites are compounds with varied chemical structures, produced by some plants and strains of microbial species. Unlike primary metabolites (nucleotides, amino acids, carbohydrates , and lipids) that are essential for growth, secondary metabolites are not. Secondary metabolites are produced or synthesized during the stationary stage. In this chapter, we will discuss secondary metabolites from natural products synthesized mainly by plants, fungi, and bacteria. Plants synthesize a large diversity of secondary metabolites; plant secondary metabolites are split into four groups namely alkaloids, phenolic compounds, terpenoids, and glucosinolates. Several classes of fungal and bacterial secondary metabolites, their sources, and pharmacological uses associated with the secondary metabolites are also discussed. Therefore, several classes of secondary metabolites are responsible for the biological and pharmacological activities of plants and herbal medicines.
... assamica (Mast.) Kitamura [1]. The production of Pu-erh tea requires special piling and aging processes which results in the unique stale aroma and a mellow, thick taste [2,3]. ...
The aroma characteristics of Pu-erh tea were studied in this work. A total of 117 volatile compounds were identified by HS-SPME combined with GC–TOF/MS, of which 29 active aroma compounds were identified by olfactometry. The active aroma compounds of Pu-erh tea were analyzed by intensity aroma (IA), aroma extraction dilution (AEDA), sensory quantification value (MF), detection frequency (DFA) and odor activity value (OAV). 24, 21 and 23 active aroma components were identified by DFA, AEDA and OAV, while 20 by IA and MF. Recombination of the obtained active aroma components indicated that OAV method was best for determining the active aroma compounds as the aroma profile of OAV recombination model was the most similar to that of Pu-erh tea sample. Omission test of the OAV recombination model furtherly identified 19 characteristic active aroma compounds of Pu-erh tea, and linalool, 1,2,3-trimenthoxybenzebe, 1,2,4-trimethoxybenzene and ɑ-ionone were the key characteristic active aromatic compounds.
... Many Aspergillus species produce and secrete various enzymes, such as α-amylase, glucoamylase, cellulase, pectinase, xylanase, hemicellulase, and protease, which are applied on an industrial scale to improve the taste of food items by breaking down proteins or lipids and developing unique flavors (Ward et al., 2005). Additionally, A. cristatum is widely used in making crimson soup from dark tea, and lovastatin, a chemical secreted by this genus, is a statin that lowers cholesterol levels (Shi et al., 2005;Zhao et al., 2013). Further studies are needed to explore the probiotic properties of individual fungal species and their role in nutrition enhancement. ...
The fungi present during pile-fermentation of Sichuan dark tea play a pivotal role in the development of its aroma and physical characteristics. Samples of tea leaves were collected on days 0 (YC-raw material), 8 (W1-first turn), 16 (W2-second turn), 24 (W3-third turn), and 32 (W4-out of pile) during pile-fermentation. High-throughput sequencing revealed seven phyla, 22 classes, 41 orders, 85 families, 128 genera, and 184 species of fungi. During fermentation, the fungal diversity index declined from the W1 to W3 stages and then increased exponentially at the W4 stage. A bar plot and heatmap revealed that Aspergillus , Thermomyces , Candida , Debaryomyces , Rasamsonia , Rhizomucor , and Thermoascus were abundant during piling, of which Aspergillus was the most abundant. Cluster analysis revealed that the W4 stage of fermentation is critical for fungal growth, diversity, and the community structure in Sichuan dark tea. This study revealed the role of fungi during pile-fermentation in the development of the essence and physical characteristics of Sichuan dark tea. This study comes under one of the Sustainable Development Goals of United Nations Organization (UNO) to “Establish Good Health and Well-Being”.
... Това се дължи на гъбичните щамове -Aspergillus tubingensis, Aspergillus wentii, Aspergillus fumigatus, Penicillium chrysogenum, Trichoderma asperellum и Trichoderma citrinoviride, които участват във ферментационните процеси на Пу-ер чай и са в състояние да продуцират значителни количества lovastatin. (12) Основните предполагаеми механизми, чрез които Пу-ер чаят успява да реализира антиобезните си ефекти, включват модулиране на AMПK (АМФ-активирани протеин кинази) и повлияване на стеароил-КoA десатураза (SCD). ...
Introduction: Overweight (obesity) is a high content of fat in the body and is associated with numerous debilitating and life threatening diseases such as cardiovascular, metabolic and many others. The potential benefits of weight reduction by consuming dietary supplements or teas made from the tea bush Camellia sinensis are a subject to an increased number of scientific researches.
The aim of the study is to collect the data and discuss the bioactive ingredients of Pu-erh tea, as well as the molecular mechanisms involved in the reduction of body weight.
Materials and Methods: The study will include researches conducted in in vitro conditions, on experimental animals, as well as clinical studies. For this purpose, there will be used databases such as Pubmed and Scince direct.
Results and Discussion: Chinese black tea (Puerh) is produced in the Yunnan province by a special technology in which leaves are fermented by using microorganisms and the final product has a unique taste, color, aroma, as well as specific biological components, such as rust-brown colored pigment – theabrownin. The possible molecular mechanisms of
the anti-obesity activity include the influence of acetyl-CoA carboxylase activity by modulation of AMPK
... Aspergillus tubingensis, Aspergillus wentii and Aspergillus fumigatus isolated from PFPT produced lovastatin https://doi.org/10.1016/j.foodchem.2020.127560 Received 24 October 2019; Received in revised form 22 June 2020; Accepted 9 July 2020 (Zhao, Pan, Liu & Li, 2013). Aspergillus spp. ...
Post-fermented Pu-erh tea (PFPT) is a microbially-fermented tea with distinct sensory qualities and multiple health benefits. Aspergillus are the dominant fungi in the fermentation and the main contributors to the characteristics of PFPT, so their underlying functions warrant detailed study. Here, tea leaves were fermented by Aspergillus niger, Aspergillus tamarii and Aspergillus fumigatus, and resulting samples (designated as Asn, Ast and Asf, respectively) were analyzed by proteomic and metabolomic methods. Changes to the composition of flavonoids, glycerophospholipids, organo-oxygen compounds and fatty acids resulting from Aspergillus fermentation were observed. Carbohydrate-active enzymes, e.g., endoglucanases and cellulases, for degradation of cellulose, starch, lignin, pectin, xylan and xyloglucan were identified. Glycoside hydrolase, glycosyltransferases, tannase, laccases, vanillyl-alcohol oxidases and benzoquinone reductase were identified and hypothesized to catalyze hydrolysis, oxidation, polymerization and degradation of phenolic compounds. Together, functions of Aspergillius were demonstrated as production of enzymes to change concentrations and compositions of metabolites in tea leaves.
... Lovastatin belongs to a group of drugs known as statins that are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Lovastatin was discovered in the late 1970s at Merck Research Laboratories (Kenilworth, NJ, USA) and is a natural compound obtainable, for example, from red rice [312] or Pu-erh tea [313]. Lovastatin is a prodrug and is widely used as a cholesterol-lowering drug and for the treatment of cardiovascular disease. ...
Selectins belong to a group of adhesion molecules that fulfill an essential role in immune and inflammatory responses and tissue healing. Selectins are glycoproteins that decode the information carried by glycan structures, and non-covalent interactions of selectins with these glycan structures mediate biological processes. The sialylated and fucosylated tetrasaccharide sLex is an essential glycan recognized by selectins. Several glycosyltransferases are responsible for the biosynthesis of the sLex tetrasaccharide. Selectins are involved in a sequence of interactions of circulated leukocytes with endothelial cells in the blood called the adhesion cascade. Recently, it has become evident that cancer cells utilize a similar adhesion cascade to promote metastases. However, like Dr. Jekyll and Mr. Hyde’s two faces, selectins also contribute to tissue destruction during some infections and inflammatory diseases. The most prominent function of selectins is associated with the initial stage of the leukocyte adhesion cascade, in which selectin binding enables tethering and rolling. The first adhesive event occurs through specific non-covalent interactions between selectins and their ligands, with glycans functioning as an interface between leukocytes or cancer cells and the endothelium. Targeting these interactions remains a principal strategy aimed at developing new therapies for the treatment of immune and inflammatory disorders and cancer. In this review, we will survey the significant contributions to and the current status of the understanding of the structure of selectins and the role of selectins in various biological processes. The potential of selectins and their ligands as therapeutic targets in chronic and acute inflammatory diseases and cancer will also be discussed. We will emphasize the structural characteristic of selectins and the catalytic mechanisms of glycosyltransferases involved in the biosynthesis of glycan recognition determinants. Furthermore, recent achievements in the synthesis of selectin inhibitors will be reviewed with a focus on the various strategies used for the development of glycosyltransferase inhibitors, including substrate analog inhibitors and transition state analog inhibitors, which are based on knowledge of the catalytic mechanism.
... Some other herbal compounds also have the ability to lower blood lipids by inhibiting the 3-hydroxy-3-methylglutaryl-CoA reductase enzyme among which one can name puerh tea and green tea (due to EGCG; Cuccioloni et al., 2011;Zhao, Pan, Liu, & Li, 2013 (Topping, 1991). and reduce blood glucose levels (Samad & Ruf, 2013). ...
The cover image is based on the Review* Effect of the Herbal medicines in obesity and metabolic syndrome: A Systematic Review and Meta-analysis of clinical trials by Moloud Payab ** et al., https://doi.org/10.1002/ptr.6547.***
... Some other herbal compounds also have the ability to lower blood lipids by inhibiting the 3-hydroxy-3-methylglutaryl-CoA reductase enzyme among which one can name puerh tea and green tea (due to EGCG; Cuccioloni et al., 2011;Zhao, Pan, Liu, & Li, 2013 (Topping, 1991). and reduce blood glucose levels (Samad & Ruf, 2013). ...
Obesity is a medical situation in which excess body fat has gathered because of imbalance between energy intake and energy expenditure. In spite of the fact that the variety of studies are available for obesity treatment and management, its “globesity” still remains a big challenge all over the world. The current systematic review and meta‐analysis aimed to evaluate the efficacy, safety, and mechanisms of effective herbal medicines in the management and treatment of obesity and metabolic syndrome in human. We systematically searched all relevant clinical trials via Web of Science, Scopus, PubMed, and the Cochrane database to assess the effects of raw or refined products derived from plants or parts of plants on obesity and metabolic syndrome in overweight and obesity adult subjects. All studies conducted by the end of May 2019 were considered in the systematic review. Data were extracted independently by two experts. The quality assessment was assessed using Consolidated Standards of Reporting Trials checklist. The main outcomes were anthropometric indices and metabolic syndrome components. Pooled effect of herbal medicines on obesity and metabolic syndrome were presented as standardized mean difference (SMD) and 95% confidence interval (CI). A total of 279 relevant clinical trials were included. Herbals containing green tea, Phaseolus vulgaris, Garcinia cambogia, Nigella sativa, puerh tea, Irvingia gabonensis, and Caralluma fimbriata and their active ingredients were found to be effective in the management of obesity and metabolic syndrome. In addition, C. fimbriata, flaxseed, spinach, and fenugreek were able to reduce appetite. Meta‐analysis showed that intake of green tea resulted in a significant improvement in weight ([SMD]: −0.75 [−1.18, −0.319]), body mass index ([SMD]: −1.2 [−1.82, −0.57]), waist circumference ([SMD]: −1.71 [−2.66, −0.77]), hip circumference ([SMD]: −0.42 [−1.02, −0.19]), and total cholesterol, ([SMD]: −0.43 [−0.77, −0.09]). In addition, the intake of P. vulgaris and N. sativa resulted in a significant improvement in weight ([SMD]: −0.88, 95 % CI: [−1.13, −0.63]) and triglyceride ([SMD]: −1.67, 95 % CI: [−2.54, −0.79]), respectively. High quality trials are still needed to firmly establish the clinical efficacy of the plants in obesity and metabolic syndrome.
... Post-fermented tea Pu-erh needs a dozen years of maturation to be considered ripened [24]. Wet piling is an alternative, affording to speed up the process. ...
Tea is one of the most popular beverages all over the world. Being an everyday drink for almost everyone, for centuries tea was considered safe and healthy. However, fungal contamination of tea at any stage of commodity production can pose a serious health hazard due to the accumulation of toxic secondary metabolites of moulds. Contemporary research revealed incidences of highly contaminated samples. Mycotoxin transfer from naturally contaminated raw tea into beverage was well studied for ochratoxin A only, and the possible leak of other mycotoxins is discussed. The results of several surveys were combined to evaluate aflatoxin B1 and ochratoxin A contamination levels in black tea and Pu-erh. Exposure estimate to aflatoxin B1 and ochratoxin A due to tea consumption was carried out based on these data. Average contamination level corresponds to the exposure of 3–40% (aflatoxin B1) and 5–24% (ochratoxin A) of mean overall estimates for different cluster diets. Lack of data does not allow the conclusion for the necessity of public health protection measures. It is necessary to perform representative studies of different kinds of tea for regulated mycotoxins at least. Contemporary techniques for analysis of mycotoxins in tea are summarised in the present review.
... levure rouge de riz, les pleurottes ou le thé fermenté(Gunde-Cimerman and Cimerman, 1995;Li et al., 2004;Zhao et al., 2013). Cependant, il semble peu probable que les doses de statine naturelle rencontrées par les patients non exposés aux statines médicamenteuses (Tableau 12) soient assez élevées ou assez régulières pour provoquer une MNAI, et suggère la nécessité d'un autre facteur déclenchant.Il existe des différences entre les patients exposés aux statines et les non-exposés. ...
Les myopathies auto-immunes (MAI), classiquement appelées myosites ou myopathies inflammatoires idiopathiques, représentent un groupe de maladies définies par des caractéristiques cliniques, histopathologiques et biologiques. Une des caractéristiques les plus notables est la présence d’auto-anticorps (aAc) chez environ 60% des patients. Les MAI regroupent : les dermatomyosites, les polymyosites, les myosites à inclusion, les myosites de chevauchement incluant le syndrome des anti-synthétases et les myopathies nécrosantes auto-immunes (MNAI). Les MNAI ont été récemment individualisées parmi les MAI comme des maladies graves fréquemment associées à la présence d’aAc dirigés contre la Signal Recognition Particle (SRP) ou la 3-Hydroxy-3-MéthylGlutaryl-CoA Réductase (HMGCR). La localisation de SRP et HMGCR étant intracellulaire, le rôle des aAc dans la physiopathologie des MNAI reste mal compris. La pathogénicité des aAc anti-SRP et anti-HMGCR envers des cellules musculaires cultivées in vitro a récemment été mise en évidence mais leurs effets in vivo demeurent inconnus.Au cours de cette thèse, j’ai étudié le rôle physiopathologique des aAc anti-SRP et anti-HMGCR in vivo chez la souris. Le transfert passif d’IgG de patients atteints de MNAI, positifs pour les aAc anti-SRP ou anti-HMGCR, à la souris sauvage entraîne un déficit musculaire. Ce déficit était prolongé chez la souris immunodéficiente Rag2-/-, et limité chez la souris déficiente pour la fraction C3 du complément. Chez les souris recevant les IgG anti-SRP+, le déficit musculaire était important et accompagné de quelques signes de nécrose myocytaire. Les IgG anti-HMGCR+ induisaient une faiblesse musculaire moindre, et des signes histopathologiques rares ou absents. Ces résultats sont en accord avec l’observation chez l’homme d’une maladie plus grave chez les patients anti-SRP+ par rapport aux patients anti-HMGCR+. La supplémentation en complément humain des souris augmentait le déficit musculaire induit par les IgG anti-HMGCR+ et de façon moindre pour les IgG anti-SRP+. En collaboration avec l’INSERM UMRS974, nous avons montré que les cibles SRP et HMGCR peuvent être détectées à la surface des fibres musculaires in vitro, suggérant qu’elles puissent être accessibles aux aAc in vivo.Ces résultats démontrent pour la première fois le rôle pathogène des aAc anti-SRP et anti-HMGCR in vivo et l’implication du complément, contribuant à une avancée dans la compréhension de la physiopathologie des MNAI.
... This mold produces lovastatin in its natural form, the so-called monacolin K, its pharmacologic active compound, and a well-known type of statin [58]. After long-term storage, Pu-erh tea is rich in Aspergillus terreus, which plays a role in its maturation and specific flavor and is also a source of lovastatin [59]. Of note, the first statin synthesized in 1976 by Akira Endo, a Japanese biochemist, was derived from the fungus species Penicillium citrinum [60]. ...
Introduction: Musculoskeletal manifestations are well-recognized side effects of treatment with statins. New advances in this field have appeared in recent years. This review focuses on the diagnosis of these conditions and their underlying pathogenesis, in particular immune-mediated necrotizing myopathy.
Areas covered: Clinical phenotypes including rhabdomyolysis, myalgia and/or mild hyperCKemia, self-limited toxin statin myopathy, and immune-mediated necrotizing myopathy are herein described. Therapeutic recommendations and a diagnostic algorithm in statin-associated myopathy are also proposed. The etiology and pathogenesis of statin-induced myopathy has mainly focused on the anti-HMGCR antibodies and the responsibility of the immune-mediated necrotizing myopathy is discussed. The fact that patients who have not been exposed to statins may develop statin-associated autoimmune myopathy with anti-HMGCR antibodies is also addressed. The literature search strategy included terms identified by searches of PubMed between 1969 and December 2017. The search terms ‘myositis’, ‘statin-induced autoimmune myopathy’, ‘immune-mediate necrotizing myopathy’, ‘statins’, ‘muscular manifestations’, and ‘anti-HMGCR antibodies’ were used.
Expert commentary: Full characterization of the known phenotypes of statin toxicity and the specific role of the anti-HMGCR in those exposed and not exposed (i.e. juvenile forms) to statins and in some types of neoplasms is of paramount relevance.
... Lovastatin (Merck's Mevacor) is a kind of statin drug like 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) used for lowering cholesterol in those with hypercholesterolemia to reduce risk of cardiovascular disease [7]. Lovastatin is a naturally occurring compound found in low concentrations in food such as oyster mushrooms [8], red yeast rice [9], and Pu-erh [10]. Lovastatin was beneficial in a lot of immunologic cardiovascular diseases and widely used in the world [11]. ...
... The first statins identified were mevastatin (mevinolin) isolated from Penicillium citrinum [110], and lovastatin (also referred to as monacolin K) isolated from Aspergillus terreus [111]. Lovasatin is also present in oyster mushrooms (Pleurotus ostreatus) [112], red yeast rice [113], and ripe (but not raw) leaves of Camellia sinensis used in the Chinese tea Pu-erh [114]. Red yeast rice is obtained by cultivation with the mold Monascus purpureus, the latter being the source of several compounds that inhibit HMG-CoA reductase including monacolin K (lovastatin) [113]. ...
The user has requested enhancement of the downloaded file.
... p0315 The first statins identified were mevastatin (mevinolin) isolated from Penicillium citrinum [110], and lovastatin (also referred to as monacolin K) isolated from Aspergillus terreus [111]. Lovasatin is also present in oyster mushrooms (Pleurotus ostreatus) [112], red yeast rice [113], and ripe (but not raw) leaves of Camellia sinensis used in the Chinese tea Pu-erh [114]. Red yeast rice is obtained by cultivation with the mold Monascus purpureus, the latter being the source of several compounds that inhibit HMG-CoA reductase including monacolin K (lovastatin) [113]. ...
Cardiovascular diseases (CVDs) are a leading cause of global morbidity, mortality, and health care spending. The current goal of the United Nations is a 25% reduction in deaths owing to noncommunicable diseases such as CVDs by 2025. The economic costs of contemporary therapeutic approaches to reduce the major CVD risk factors of hyperlipidemia, atherosclerosis, and hypertension cannot be sustained on a global scale. Novel sources of bioactive molecules for use in low cost therapies will be essential to accomplish this goal. In this chapter, we review the natural products containing bioactivities for which compelling evidence of efficacy in ameliorating hyperlipidemia, atherosclerosis, and hypertension has been obtained in the laboratory or a clinical setting. The pathophysiological basis of hyperlipidemia, atherosclerosis, and hypertension and current synthetic drug therapies are reviewed and the major sources and candidate bioactive molecules as well as their postulated mechanism(s) of action are discussed.
... including in the fruiting bodies or mycelia of Agaricus, Antrodia, Ganoderma, Ophiocordyceps and Pleurotus species 91,92 , as well as in Chinese fermented pu-erh tea (FIG. 1,2) 93 . Compounds such as EGCG also inhibit HMG-CoA reductase activity in vitro 94 , and might contribute to the reduction of hyperlipidaemia and lipid deposition in vivo. ...
Obesity is reaching global epidemic proportions as a result of factors such as high-calorie diets and lack of physical exercise. Obesity is now considered to be a medical condition, which not only contributes to the risk of developing type 2 diabetes mellitus, cardiovascular disease and cancer, but also negatively affects longevity and quality of life. To combat this epidemic, anti-obesogenic approaches are required that are safe, widely available and inexpensive. Several plants and mushrooms that are consumed in traditional Chinese medicine or as nutraceuticals contain antioxidants, fibre and other phytochemicals, and have anti-obesogenic and antidiabetic effects through the modulation of diverse cellular and physiological pathways. These effects include appetite reduction, modulation of lipid absorption and metabolism, enhancement of insulin sensitivity, thermogenesis and changes in the gut microbiota. In this Review, we describe the molecular mechanisms that underlie the anti-obesogenic and antidiabetic effects of these plants and mushrooms, and propose that combining these food items with existing anti-obesogenic approaches might help to reduce obesity and its complications.
... 27 The statin compound lovastatin has been identified in Puer tea, 28 and lovastatin levels increase with fermentation of tea leaves. 29,30 However, the levels of statins that can be found in some sources of Puer tea are several hundredfold lower than a low dose of statin delivered as a drug for hyperlipidemia, 29,31 and thus quite unlikely to contribute significantly to the overall effects of Puer tea consumption. ...
Objective
The goal for this study was to evaluate the effects of daily consumption of Puer tea extract (PTE) on body weight, body-fat composition, and lipid profile in a non-Asian population in the absence of dietary restrictions.
Materials and methods
A randomized, double-blind, placebo-controlled study design was used. A total of 59 overweight or mildly obese subjects were enrolled upon screening to confirm fasting cholesterol level at or above 220 mg/dL (5.7 mmol/dL). After giving informed consent, subjects were randomized to consume PTE (3 g/day) or placebo for 20 weeks. At baseline and at 4-week intervals, blood lipids, C-reactive protein, and fasting blood glucose were evaluated. A dual-energy X-ray absorptiometry scan was performed at baseline and at study exit to evaluate changes to body composition. Appetite and physical and mental energy were scored at each visit using visual analog scales (0–100).
Results
Consumption of PTE was associated with statistically significant weight loss when compared to placebo (P<0.05). Fat loss was seen for arms, legs, and the gynoid region (hip/belly), as well as for total fat mass. The fat reduction reached significance on within-group analysis, but did not reach between-group significance. Consumption of PTE was associated with improvements to lipid profile, including a mild reduction in cholesterol and the cholesterol:high-density lipoprotein ratio after only 4 weeks, as well as a reduction in triglycerides and very small-density lipoproteins, where average blood levels reached normal range at 8 weeks and remained within normal range for the duration of the study (P<0.08). No significant changes between the PTE group and the placebo group were seen for fasting glucose or C-reactive protein. A transient reduction in appetite was seen in the PTE group when compared to placebo (P<0.1).
Conclusion
The results from this clinical study showed that the daily consumption of PTE was associated with significant weight loss, reduced body mass index, and an improved lipid profile.
... The closest sequences were assigned to an undescribed Leptosphaeria sp. isolated from plant specimens in China [31] The genus Leptosphaeria includes a large number of species mainly considered saprobic or necrotrophic on stems and leaves. The genus also comprises highly pathogenic species such as L. maculans and L. biglobosa, the causal agents of 'blackleg' of Brassicae crops [32], and L. coniothyrium causal agent of stem canker of raspberry and roses [33]. ...
Recent disease outbreaks caused by alien invasive pathogens into European forests
posed a serious threat to forest sustainability with relevant environmental and economic
effects. Many of the alien tree pathogens recently introduced into Europe were not
previously included on any quarantine lists, thus they were not subject to phytosanitary inspections.
The identification and description of alien fungi potentially pathogenic to native
European flora before their introduction in Europe, is a paramount need in order to limit
the risk of invasion and the impact to forest ecosystems. To determine the potential invasive
fungi, a sentinel trees plot was established in Fuyang, China, using healthy seedlings
of European tree species including Quercus petreae, Q. suber, and Q. ilex. The fungal assemblage
associated with symptomatic specimens was studied using the tag-encoded
454 pyrosequencing of the nuclear ribosomal internal transcribed spacer-1 (ITS 1). Taxa
with probable Asiatic origin were identified and included plant pathogenic genera. These
results indicate that sentinel plants may be a strategic tool to improve the prevention
of bioinvasions.
... For example, the endophytic A. fumigatus of the conifer Podocarpus macrophyllus produces the antitumor agent taxol (Sun et al. 2008); gliotoxin and its derivatives are also produced by A. fumigatus H1204 isolated from a marine source (Han et al. 2007); and compounds with antimycotic activity against the yeast, Malassezia furfur, have been reported in A. fumigatus (Kang et al. 2013). A. fumigatus isolates from Pu-erh tea have produced lovastatin (Zhao et al. 2013), a compound with cholesterol-lowering properties. In view of its widespread occurrence in fermented foods with a long history of safe consumption, the use of a suitable strain of A. fumigatus in combination with a well-controlled fermentation process may be quite satisfactory for producing theabrownins from infusions of sun-dried green tea. ...
Theabrownins (TB) are water-soluble phenolic compounds associated with the various health benefits of Pu-erh tea, a post-fermented Chinese dark tea. This work reports on the production of theabrownins from infusions of sun-dried green tea leaves using a pure culture of Aspergillus fumigatus isolated from a solid-state Pu-erh tea fermentation. A theabrownins yield of 158 g kg(-1) sun-dried green tea leaves was obtained in 6 days at 45 °C in an aerobic fermentation. In a 2 l fermenter, the yield of theabrownins was 151 g kg(-1) sun-dried green tea leaves in 48 h of aerobic culture (45 °C, 1 vvm aeration rate, 250 rpm agitation speed). Extracellular polyphenol oxidase and peroxidase of A. fumigatus contributed to this bioconversion. Repeated batch fermentation process was used for producing theabrownins but was less productive than the batch process.
Statins are the first line of treatment for both primary and secondary prevention of atherosclerotic cardiovascular disease. Despite the positive effects of statins on car-diovascular events, not all patients can use them at an optimized dose. The reason for this is the skeletal muscle side effects, termed statin-associated muscle symptoms (SAMS). Despite extensive research, the precise pathophysiology of SAMS remains unclear and multiple mechanisms may contribute to this phenomenon. Various therapeutic options are available for the management of SAMS, ranging from rechallenging with the same or a different statin to utilizing non-statin therapeutic alternatives in patients intolerant to statins. However, the lack of consensus on the definition of SAMS, the absence of a definitive diagnostic test, and lack of a universally accepted management algorithm pose a great challenge in dealing with this entity. This review aims to explore the various pathophysiological mechanisms involved in SAMS and understand the difference between self-limited toxic myopathy and immune-mediated myopathy requiring immunomodulatory therapy. The conundrum of statin withdrawal , tapering, and rechallenge in SAMS will also be explored in detail along with the newer non-statin therapies that are available.
Penicillium is universal in dark tea, and Penicillium citrinum can produce a kidney toxin called citrinin (CIT). Determining CIT is difficult because of the complexity of the dark tea substrate and the diversity of CIT-producing fungi. Therefore, this study established a real-time PCR (qPCR) detection method for CIT-related synthetic genes (ctnD, orf1, ctnA, pksCT, orf5, orf7, and ctnG) in Liupao tea and determined the content of CIT in samples at different production stages and the toxin-producing abilities of fungi (Aspergillus oryzae, etc.) in Liupao tea. CIT was found in all samples during the pile-fermentation process of Liupao tea, and CIT was detected in two samples during the aging process. The established method demonstrated good sensitivity and specificity in detecting CIT-related synthetic genes. The reaction efficiency was within the preferred range of 100 ± 10%. CIT was not detected or was below the detection limit when the Ct value of one or more related synthetic genes was greater than 33.5. Therefore, the established qPCR method can effectively predict the production of CIT in Liupao tea, and it is applicable to the judgment of whether fungi produce CIT.
Lovastatin is a statin produced by Monascus purpureous-fermented pu-erh tea, which is used in the treatment of cardiovascular diseases and prostate cancer. Bacteria-mediated cancer immunotherapy (BCI), which is an effective antitumor strategy compared with conventional immunotherapies, targets neutrophil infiltration associated with tumor recurrence and metastasis. In mouse colon cancer models, combination treatment with lovastatin and BCI suppressed tumor progression by extending the survival of tumor-colonizing bacteria. We used zebrafish live imaging to show that lovastatin decreases the recruitment of neutrophils to the inflammatory site by inducing neutrophil apoptosis via phosphorylation of ERK and AKT. The present findings suggest that the combination of BCI with lovastatin or fermented pu-erh tea is an effective approach compared with conventional cancer immunotherapy.
Pu-erh tea is a post-fermentation tea with unique flavor and multiple health benefits. Due to the various microorganisms involved in the post-fermentation process, Pu-erh tea contains highly complex components, which have rich interactions with the gut microbiomes (GMs). Because the structure and homeostasis of GMs are closely related to human wellness and the various diseases progress, the beneficial effects of Pu-erh tea on GMs have a great potential for application in health care. However, there is no systematic summary of the bioactive components of Pu-erh tea, and their effects on the GMs. Here, we review the current studies on the effects of Pu-erh tea and its bioactive components on the structure of GMs as well as on health improvement, and further discuss the relevant quality indicators. This “components – function - indicators” clue will hopefully stimulate the standardization of Pu-erh tea fermentation process and the development of its functional products.
Ripened Pu-erh tea is a traditional microbial-fermented tea with multiple beneficial effects and the genus Aspergillus were considered as the dominant fungi. In this study, six Aspergillus and one Penicillium fungi, abbreviated as AniPT1, AsyPT2, ApaPT3, AsePT4, PmaPT5, AusPT6 and AtaPT7, were inoculated into sun-dried green tea-leaves for the microbial fermentation. Based on 42 chemical components belonging to several classes as polyphenols, amino acids and purine alkaloids, PCA and HCA revealed the significant differences in tea-leaves microbial fermentation of seven tea-derived fungi. Most of catechins, flavonoids and free amino acids were decreased highly significantly (p < 0.001), while theabrownins, theaflavins and gallic acid contents were increased highly significantly (p < 0.001) in all microbial fermentation. Additionally, several tea-derived fungi contributed to the accumulation of (+)-catechin, (-)-epicatechin, kaempferol, myricetin, theophylline, L-methionine, L-tryptophan, L-cysteine, L-histidine and γ-aminobutyric acid, and the improvement of antioxidant activity in tea-leaves after inoculated fermentation. Particularly, AsyPT2 converted caffeine into theophylline mainly. The bivariate correlation analysis confirmed the extremely significantly (p < 0.001) positive correction of gallic acid and kaempferol to antioxidant activity in fermented tea-leaves. This study provided reference for the application of tea-derived fungi in ripened Pu-erh tea.
Purpose of review
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are a class of lipid-lowering medications by inhibiting the enzyme HMG-CoA reductase. Statins are important drugs for the prevention of cardiovascular disease. The prominent value of statins is well established during the past three decades. The efficacy and safety of statins have been evaluated in many large randomized controlled trials.
Recent findings
Currently, emerging concerns with statin-induced liver toxicity (SILT) and muscle toxicity (SIMT) have been introduced. However, exact mechanisms of SILT and SIMT have not been well understood. Moreover, there is an increasing concern currently about their safety associated with genetic polymorphisms. Thus, this article reviews the mechanisms of statin-drug interactions and their adverse effects with a particular focus on SILT and SIMT. It is recommended that the specific pharmacology for the different statins should be understood to maximize their benefit and minimize statin-induced toxicity. Significant toxicity may be induced by statin-drug interactions, and understanding how certain drugs interact with statins will help physicians in safely prescribing these agents.
Lovastatin exists in red yeast rice, post-fermented pu-erh tea, oyster mushroom, and different varieties of fungi. It is used to treat dyslipidemia, prevent cardiovascular disease, or combined with dietary interventions. However, it is not effective in treatment of receptor-negative homozygous familial hypercholesterolemia. Lovastatin was originally known as an HMG-CoA reductase inhibitor, thus reducing cholesterol biosynthesis; more complicated mechanism of actions were discovered later. Pharmaceutical preparation strategies are needed to improve the absorption and bioavailability of lovastatin. Lovastatin can lead to drug-drug interactions and several adverse reactions though. Chemical structure modifications led to series of new statins, one of which has been list in the best-selling drugs in the history of pharmaceuticals.
Koji products have been considered as an effective fermented food consumed in East Asia with many health benefits. Particularly, rice koji with Aspergillus terreus (RAT) has been reported to be able to prevent hyperlipidemia and hepatic steatosis through regulating cholesterol synthesis. Despite its biological activities, there is a lack of comprehensive information to give an assurance of its safety. Therefore, the objective of this study was to perform a series of toxicological studies (repeated dose oral toxicity and genotoxicity) according to test guidelines published by the Organization for Economic Cooperation and Development. Along with acute toxicity study using rats and beagle dogs, a 13-week toxicity study revealed no clear RAT-related toxic changes, including body weight, mortality, hematology, serum biochemistry, organ weight, and histopathology after oral administration at doses of 500, 1000, and 2000 mg/kg BW. The no-observed-adverse-effect level of RAT was considered to be more than 2000 mg/kg BW/day in rats of both genders. In addition, potential genotoxicity was evaluated using a standard battery of tests (Ames test, chromosome aberration assay, and micronucleus assay) which revealed that RAT showed no genotoxicity. Accordingly, these results suggest that RAT is a safe and non-toxic functional food for human consumption at proper dose.
Matrix effect-free UHPLC–MS/MS method was developed and validated for the determination of cholesterol-lowering lovastatin in food samples represented by Pu-erh tea, oyster mushroom, and red yeast rice. The resulting method was fully validated in terms of intra-day and inter-day precision, accuracy, linearity, range, LOD, LOQ, and matrix effects. The matrix effect phenomenon evaluated by comparison of slopes of calibration curves was completely eliminated by solid-phase extraction based on the technique of molecularly imprinted polymers (MIPs). Comparison of elution profiles obtained on the MIP and corresponding control non-imprinted polymer (NIP) showed selectivity of the extraction procedure. In addition, selectivity of the MIP material and the molecularly imprinted solid-phase extraction (MISPE) was also proved by experiments evaluating retention of analytes physico-chemically similar to the target molecule. Extraction recoveries of these analytes represented by estrogen derivatives (estrone, estriol, 17α‐ethinylestradiol, and β-estradiol) were very low or even null. Synthesis and preparation of the resulting MIP sorbent was characterized by excellent repeatability expressed as RSD 7.7% (n = 9) of extraction recoveries. The determined capacity of the MIP material reaching 375 ng/mg is sufficient for analysis of the evaluated statin in its natural sources. Suitability of the resulting MISPE-UHPLC-MS/MS procedure for real sample analysis was verified by the determination of lovastatin in one dietary supplement based on the red yeast rice with a given amount of the target analyte. Finally, three mushroom and fifteen tea samples obtained in Czech food stores and tearooms were subjected to analysis. Low or null amount of lovastatin was found in these samples.
Methane produced by the methanoarchaeon Methanobrevibacter smithii (M. smithii) has been linked to constipation, irritable bowel syndrome with constipation (IBS-C), and obesity. Lovastatin, which demonstrates a cholesterol-lowering effect by the inhibition of HMG-CoA reductase, may also have an anti-methanogenesis effect through direct inhibition of enzymes in the archaeal methanogenesis pathway. We conducted protein-ligand docking experiments to evaluate this possibility. Results are consistent with recent clinical findings.
METHODS: F420-dependent methylenetetrahydromethanopterin dehydrogenase (mtd), a key methanogenesis enzyme was modeled for two different methanogenic archaea: M. smithii and Methanopyrus kandleri. Once protein models were developed, ligand-binding sites were identified. Multiple ligands and their respective protonation, isomeric and tautomeric representations were docked into each site, including F420-coenzyme (natural ligand), lactone and β-hydroxyacid forms of lovastatin and simvastatin, and other co-complexed ligands found in related crystal structures.
RESULTS: 1) Generally, for each modeled site the lactone form of the statins had more favorable site interactions compared to F420; 2) The statin lactone forms generally had the most favorable docking scores, even relative to the native template PDB ligands; and 3) The statin β-hydroxyacid forms had less favorable docking scores, typically scoring in the middle with some of the F420 tautomeric forms. Consistent with these computational results were those from a recent phase II clinical trial (NCT02495623) with a proprietary, modified-release lovastatin-lactone (SYN-010) in patients with IBS-C, which showed a reduction in symptoms and breath methane levels, compared to placebo.
CONCLUSION: The lactone form of lovastatin exhibits preferential binding over the native-F420 coenzyme ligand in silico and thus could inhibit the activity of the key M. smithii methanogenesis enzyme mtd in vivo. Statin lactones may thus exert a methane-reducing effect that is distinct from cholesterol lowering activity, which requires HMGR inhibition by statin β-hydroxyacid forms.
Methane produced by the methanoarchaeon Methanobrevibacter smithii ( M. smithii) has been linked to constipation, irritable bowel syndrome with constipation (IBS-C), and obesity. Lovastatin, which demonstrates a cholesterol-lowering effect by the inhibition of HMG-CoA reductase, may also have an anti-methanogenesis effect through direct inhibition of enzymes in the archaeal methanogenesis pathway. We conducted protein-ligand docking experiments to evaluate this possibility. Results are consistent with recent clinical findings.
METHODS: F420-dependent methylenetetrahydromethanopterin dehydrogenase ( mtd), a key methanogenesis enzyme was modeled for two different methanogenic archaea: M. smithii and Methanopyrus kandleri. Once protein models were developed, ligand-binding sites were identified. Multiple ligands and their respective protonation, isomeric and tautomeric representations were docked into each site, including F420-coenzyme (natural ligand), lactone and β-hydroxyacid forms of lovastatin and simvastatin, and other co-complexed ligands found in related crystal structures.
RESULTS: 1) Generally, for each modeled site the lactone form of the statins had more favorable site interactions compared to F420; 2) The statin lactone forms generally had the most favorable docking scores, even relative to the native template PDB ligands; and 3) The statin β-hydroxyacid forms had less favorable docking scores, typically scoring in the middle with some of the F420 tautomeric forms. Consistent with these computational results were those from a recent phase II clinical trial (NCT02495623) with a proprietary, modified-release lovastatin-lactone (SYN-010) in patients with IBS-C, which showed a reduction in symptoms and breath methane levels, compared to placebo.
CONCLUSION: The lactone form of lovastatin exhibits preferential binding over the native-F420 coenzyme ligand in silico and thus could inhibit the activity of the key M. smithii methanogenesis enzyme mtd in vivo. Statin lactones may thus exert a methane-reducing effect that is distinct from cholesterol lowering activity, which requires HMGR inhibition by statin β-hydroxyacid forms.
Methane produced by the methanoarchaeon Methanobrevibacter smithii ( M. smithii) has been linked to constipation, irritable bowel syndrome with constipation (IBS-C), and obesity. Lovastatin, which demonstrates a cholesterol-lowering effect by the inhibition of HMG-CoA reductase, may also have an anti-methanogenesis effect through direct inhibition of enzymes in the archaeal methanogenesis pathway. We conducted protein-ligand docking experiments to evaluate this possibility. Results are consistent with recent clinical findings.
METHODS: F420-dependent methylenetetrahydromethanopterin dehydrogenase ( mtd), a key methanogenesis enzyme was modeled for two different methanogenic archaea: M. smithii and Methanopyrus kandleri. Once protein models were developed, ligand-binding sites were identified. Multiple ligands and their respective protonation, isomeric and tautomeric representations were docked into each site, including F420-coenzyme (natural ligand), lactone and β-hydroxyacid forms of lovastatin and simvastatin, and other co-complexed ligands found in related crystal structures.
RESULTS: 1) Generally, for each modeled site the lactone form of the statins had more favorable site interactions compared to F420; 2) The statin lactone forms generally had the most favorable docking scores, even relative to the native template PDB ligands; and 3) The statin β-hydroxyacid forms had less favorable docking scores, typically scoring in the middle with some of the F420 tautomeric forms. Consistent with these computational results were those from a recent phase II clinical trial (NCT02495623) with a proprietary, modified-release lovastatin-lactone (SYN-010) in patients with IBS-C, which showed a reduction in symptoms and breath methane levels, compared to placebo.
CONCLUSION: The lactone form of lovastatin exhibits preferential binding over the native-F420 coenzyme ligand in silico and thus could inhibit the activity of the key M. smithii methanogenesis enzyme mtd in vivo. Statin lactones may thus exert a methane-reducing effect that is distinct from cholesterol lowering activity, which requires HMGR inhibition by statin β-hydroxyacid forms.
This study aimed to characterize the thermophilic fungi in pile-fermentation process of Pu-erh tea. Physicochemical analyses showed that the high temperature and low pH provided optimal conditions for propagation of fungi. A number of fungi, including Blastobotrys adeninivorans, Thermomyces lanuginosus, Rasamsonia emersonii, Aspergillus fumigatus, Rhizomucor pusillus, Rasamsonia byssochlamydoides, Rasamsonia cylindrospora, Aspergillus tubingensis, Aspergillus niger, Candida tropicalis and Fusarium graminearum were isolated as thermophilic fungi under combination of high temperature and acid culture conditions from Pu-erh tea pile-fermentation. The fungal communities were analyzed by PCR-DGGE. Results revealed that those fungi are closely related to Debaryomyces hansenii, Cladosporium cladosporioides, A. tubingensis, R. emersonii, R. pusillus, A. fumigatus and A. niger, and the last four presented as dominant species in the pile process. These four preponderant thermophilic fungi reached the order of magnitude of 10(7), 10(7), 10(7) and 10(6)copies/g dry tea, respectively, measured by real-time quantitative PCR (q-PCR). The results indicate that the thermophilic fungi play an important role in Pu-erh tea pile fermentation.
Statins are potent inhibitors of the enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) that catalyzes the rate limiting step in cholesterol biosynthesis pathway. Statins lowers the plasma cholesterol level, thus effective in the treatment of hypercholesterolemia. Statins are compounds of natural origin that are biosynthesized as secondary metabolites of filamentous fungi and act as competitive inhibitors of HMGR. Sales of statins have dominated the pharmaceutical market in recent years, consistently ranking as the number one class of drugs, so are called “the golden child” for pharmaceutical companies. Statins have also been reported as a potential therapeutic agent in the regulation of inflammatory and immune response, bone turnover, neovascularisation, vascular tone, and arterial pressure along with hypocholestremic property. With the emerging multiple therapeutic effects, the wonder drugs “statins” are proving to be much more powerful drugs than ever thought
The pure lovastatin-producing strains isolated from Pu-erh tea such as Aspergillus fumigatus, Penicillium chrysogenum, Aspergillus wenti and Aspergillus tubingensis, were inoculated individually in CYA medium with different tea polyphenol concentrations. The contents of lovastatin in the medium were assayed by HPLC. Results showed that tea polyphenol had the obvious inhibitory effects on Aspergillus fumigatus (10-day incubation), Penicillium chrysogenum and Aspergillus wenti (both incubated for 5 days) to produce lovastatin. And during the rest incubating period of 5 to 15 days for Aspergillus wenti, and 10 to 15 days for Penicillium chrysogenum and Aspergillus fumigatus, tea polyphenol presented improved effects significantly on them to produce lovastatin compared to the control, and the maximum yield increased by 22.79% (Aspergillus wenti incubated on the medium with 10% tea polyphenol for 10 days). Moreover, when Aspergillus tubingensis was cultured on the medium with 30% tea polyphenol for 10 days, tea polyphenol promoted it to produce lovastatin with the maximum yield improved by 17.69%.
Pu-erh tea is one sort of unique Chinese post-fermented tea. Fungi play an important role in forming its special flavor, taste and healthy function During the post-fermentation process of Pu-erh tea, meanwhile, some harmful fungi may bring potential safety hazards to the production of Pu-erh tea. This paper summarizes recent advances on the Fungi of Pu-erh ripe tea,which concerned about fungal colonization, metabolism and safety of fungi.
Aroma volatiles from ripened and raw pu-erh tea were extracted by headspace solid-phase microextraction (HS-SPME) and simultaneous distillation-extraction (SDE). They were then characterized and identified using gas chromatography-olfactometry (GC-O) and gas chromatography-mass spectrometry (GC-MS). The conditions of HS-SPME including fiber selections and sampling condition optimization have been previously investigated. With the two methods, 39 and 33 aroma-active compounds were detected and characterized in ripened and raw pu-erh tea samples, respectively. The aroma-active compounds with similar sensory descriptors were grouped into the same category, and the sum of individual aroma intensity values within each category showed that the floral aroma (33.01 %), stale/musty aroma (25.24 %), and woody aroma (11.17 %) were the major aroma categories in ripened pu-erh tea. Alcohols (floral aroma notes), methoxyphenolic compounds (stale/musty aroma notes), and ketones (woody or floral aroma notes) play a vital role in the special flavor of ripened pu-erh tea. In raw pu-erh tea, the floral aroma (38.62 %) and fruity aroma (16.55 %) were the major aroma categories. These aromas were closely related to the characteristics of raw pu-erh tea aroma and its sensory perception.
Overgrowth by spreading molds such as Rhizopus and Mucor species is a problem with fungal enumeration media used for foods. Thirty-one antifungal compounds were surveyed for their ability to selectively inhibit such fungi while allowing growth of mycotoxigenic molds and other species of significance in food spoilage. Dichloran (2,6 dichloro-4-nitroaniline) restricted growth of Rhizopus stolonifer while allowing satisfactory growth of the other test molds. Three Rhizopus and Mucor species were encountered that were not inhibited by dichloran; these were controlled by the addition of rose bengal. The optimal medium, designated DRBC, contained 2 micrograms of dichloran and 25 micrograms of rose bengal per ml. DRBC, in pure culture tests and with food samples, restricted the colony size of spreading molds and recovered a wider range of species in higher numbers than other enumeration media.
The determination of eight components including CaO in converter slag by X-ray fluorescence spectrometry combined with pressing method was studied. The effects of sample preparation conditions, instrument parameters, matrix interference and curve fitting were investigated. Proper grinding time, sample granularity, pressing time and pressure were obtained. The analytical conditions such as channel type, crystal type, detector type, tube voltage and tube current were investigated to find the optimal analytical parameters. The calibration curve was established by characterization of the samples matrix-matched with determined samples to eliminate matrix interference. The interference of coexisting elements with the determination of FeO was eliminated by empirical coefficient method. This method had wide determination range, high precision and good stability. The relative standard deviations were all less than 2%. The measuring errors of standard sample accorded with the allowable value of GB method. Compared with chemical analysis and ICP-AES, this method had many merits such as simple operation, easy to learn and low cost. This method was satisfactory for the demands of actual production.
Pu-Erh tea is a fermented tea produced in Yunnan area, a southwestern part of China. The manufacture of Pu-Erh tea involves natural fermentation and prolonged storage at ambient temperature. Lovastatin was identified in batches of Pu-Erh tea. This study demonstrated that uptake of Pu-Erh tea reduced plasma cholesterol and triacylglycerol in cholesterolfed hamsters. Results also suggested that the cholesterollowering effect of Pu-Erh tea was caused by a combination of lovastatin and tea polyphenols. Although the content of EGCG was low, Pu-Erh tea yet exhibited strong antioxidant activities that scavenged DPPH radical and inhibited LDL oxidation in vitro and ex vivo. This study indicates that Pu-Erh tea drinking may reduce the risk factors in atherosclerosis-related ischemic heart disease.
The 5.8S gene and flanking internal transcribed spacers (ITS1 and ITS2) of the rDNA were amplified from total DNA extracted from frond tissues of Livis-tona chinensis with universal and fungal-specific primers. These amplified fragments were cloned and sequenced. Phylogenetic analysis based on the 5.8S gene sequences indicated that the six clone sequences obtained were of different origins. Five sequences, P1-9, P2-6, P4-4, P4-5, and P4-7, belonged to the fungi and one sequence, P3-2, belonged to the plants. P1-9 was inferred to belong to the Basidiomycota based on the phylogenetic analysis of the 5.8S gene sequences but could not be identified to lower taxonomic levels. Further identification of the other four fungal clones to lower taxonomic levels was attempted based on phylogenetic analysis and sequence comparison of both the conserved 5.8S gene and the variable ITS regions. The origin of P2-6 was identified to be Glomer-ella and its anamorph Colletotrichum, the origins of P4-5 and P4-7 were Mycosphaerella and its anamorph Cladosporium, and the origin of P4-4 was the Herpo-trichiellaceae. The direct approach to detection and taxonomic placement of endophytic fungi within host tissue without the need for conventional in vitro cul-turing is discussed.
Mevinolin, a fungal metabolite, was isolated from cultures of Aspergillus terreus. The structure and absolute configuration
of mevinolini and its open acid form, mevinolinic acid, were determined by a combination of physical techniques. Mevinolin
was shown to be 1,2,6,7,8,8a-hexahydro-beta, delta-dihydroxy-2,6-dimethyl-8-(2-methyl-1-oxobutoxy)-1-naphthalene-hepatanoic
acid delta-lactone. Mevinolin in the hydroxy-acid form, mevinolinic acid, is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme
A reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34]; its Ki of 0.6 nM can be compared to 1.4 nM for
the hydroxy acid form of the previously described related inhibitor, ML-236B (compactin, 6-demethylmevinolin). In the rat,
orally administered sodium mevinolinate was an active inhibitor of cholesterol synthesis in an acute assay (50% inhibitory
dose = 46 microgram/kg). Furthermore, it was shown that mevinolin was an orally active cholesterol-lowering agent in the dog.
Treatment of dogs for 3 weeks with mevinolin at 8 mg/kg per day resulted in a 29.3 +/- 2.5% lowering of plasma cholesterol.
Pu‐erh tea is a popular beverage in Southeast Asia, especially in many areas of China. Natural fungal inoculation and fermentation form its special quality and function in health care. At the same time, a common assumption is that unknown fungi from natural inoculation may pose a risk for safety of drinking the beverage, leading to an urgent need for a thorough fungal survey of Pu‐erh tea. The present paper reports the natural fungal colonizations isolated from 60 representative samples. The results of the survey showed that the fungal colonizations were isolated from all the samples studied, ranging from 1.6 × 10 ³ to 1.16 × 10 ⁵ cfu/g, and 62 isolates were identified to belong to 41 species of 19 genera, including 13 species of Aspergillus and seven species of Penicillium, and 21 species of other genera. The predominant fungi were yeasts and different species of the genus Aspergillus. The concrete species of the dominant fungi varied with environment conditions of various production places. Sample parameters such as water content, A W , pH, polyphenol content were recorded, though they appeared to have no obvious effects on the total number of fungi, whereas processing and storage methods evidently affected total number of fungi. Some species of fungi such as Aspergillus fumigatus, Penicillium spp., Trichoderma spp. and Fusarium culmorum, etc., which maybe excrete toxic metabolites, were isolated in the survey. Further evaluation on the safety of these fungi isolated from Pu‐erh tea products is needed.
PRACTICAL APPLICATIONS
This study investigated the fungal colonizatins exisiting in Pu‐erh tea and some parameters concerning the storage of Pu‐erh tea. These findings will help to evaluate the safety of Pu‐erh tea products, and also facilitate the formulation of microbiologically sound methods for the manufacture and storage of Pu‐erh tea, especially for the supervision of microbic fermentation during the process of ripe Pu‐erh tea manufacture, thus contributing to avoid the contamination from toxigenic or potentially toxic fungi, and to ensure the safety of drinking Pu‐erh tea.
Puer tea is a unique Chinese fermented tea with natural flora manufactured in Yunnan Province of China. Very complex changes take place to form special quality and flavor characteristics in Puer tea due to the coordination of microbial metabolic action and natural oxidation. This paper investigates the isolation and identification of fungi responsible for the fermentation and the development of main volatile compounds of Puer tea during the fermentation process by means of GC/MS. Aldehydes and ketones in parched green tea (raw material) with low boiling-points decreased significantly, while the amount of terpene alcohols – such as linalool and linalool oxides, methoxybenzene and derivatives, and indole – increased remarkably from the parched green tea to the Puer tea product after the manufacturing process. Degradation caused by heat and microbial growth at the piling stage likely played a key role in the generation of these compounds that contributed to the aromatic characteristics of Puer tea. It is hypothesized that the fungus Aspergillus niger plays a decisive role in the development of the volatile compounds.
The 5.8S gene and flanking internal transcribed spacers (ITS1 and ITS2) of the rDNA were amplified from total DNA extracted from frond tissues of Livistona chinensis with universal and fungal-specific primers. These amplified fragments were cloned and sequenced. Phylogenetic analysis based on the 5.8S gene sequences indicated that the six clone sequences obtained were of different origins. Five sequences, P1-9, P2-6, P4-4, P4-5, and P4-7, belonged to the fungi and one sequence, P3-2, belonged to the plants. P1-9 was inferred to belong to the Basidiomycota based on the phylogenetic analysis of the 5.8S gene sequences but could not be identified to lower taxonomic levels. Further identification of the other four fungal clones to lower taxonomic levels was attempted based on phylogenetic analysis and sequence comparison of both the conserved 5.8S gene and the variable ITS regions. The origin of P2-6 was identified to be Glomerella and its anamorph Colletotrichum, the origins of P4-5 and P4-7 were Mycosphaerella and its anamorph Cladosporium, and the origin of P4-4 was the Herpotrichiellaceae. The direct approach to detection and taxonomic placement of endophytic fungi within host tissue without the need for conventional in vitro culturing is discussed.
As the consumption of Puerh tea is booming because of its multiple health-promoting effects, the possible health risks resulting from long-term exposure to metals contained in this tea need to be evaluated. To assess the human risk associated with drinking Puerh tea, concentrations of aluminium, lead, cadmium, mercury, zinc, copper and arsenic were determined in samples of Puerh tea, tea leaves from the plants, and planted soil collected from the Yunnan province, China. Site-specific exposure parameters such as body weight and consumption rate of Puerh tea were investigated in Kunming and Puer cities using face-to-face surveys. Health risks were evaluated for the inhabitants of Kunming and Puer cities by gender and by age groups. Although the Puerh tea plant easily absorbs aluminium from soil, the concentrations of Al and six other elements in Puerh tea were all far below the safety concentration limits of China. Both the HQ (Hazard Quotient) values for single elements and the HI (Hazard Index) value for all seven elements were far below one, indicating no non-carcinogenic risks from these seven elements for inhabitants of Kunming and Puer under the current consumption rates of Puerh tea. However, probabilistic estimation of carcinogenic risk shows that the 95th percentile carcinogenic rate of arsenic in Puerh tea approaches the accepted risk level of 10(-4) for the highest exposure group. Therefore, the arsenic in Puerh tea is of concern.
The effect of water extracts of Pu-Erh tea (products of Yunnan district, China, preserved for 2 or 20 years) and of green tea (products of Shizuoka prefecture, Japan) on lipid level, tissue weight, lipoprotein lipase (LPL) and adrenalin-induced lipolytic (AIL) activity in rats were examined. Female Wistar rats (8 weeks old) were fed a diet containing 1% cholesterol and given the above tea extracts in drinking water for 8 or 16 weeks ad libitum. The levels of plasma cholesterol ester in rats given Pu-Erh tea or green tea were significantly lower than those of control rats after 6-8 weeks, though the difference became smallar after 10 weeks. The triglyceride (TG) level in plasma was also low in rats given Pu-Erh tea for 16 weeks. This effect on TG was not observed in the case of green tea. Among 6 organs or tissues of rats examined, the weight of abdominal adipose tissue was significantly lower in rat fed Pu-Erh tea for 16 weeks. The LPL activity in abdominal adipose tissue tended to be low (though not statistically significant), while the activity of AIL was significantly elevated in rats given Pu-Erh tea for 8 or 16 weeks. A negative correlation was observed between AIL activity and the ratio of adipose tissue/body weight. These data suggest that the successive administration of Pu-Erh tea could stimulate the degradation of TG in adipose tissue and thereby decrease its weight.
A simple screening method has been developed for detecting ochratoxin production by fungi, based on high-performance liquid chromatographic determinations on extracts obtained from agar plugs cut from pure Petri dish cultures. Two culture media. Yeast Extract Sucrose agar and Czapek Yeast Extract agar, and three extraction solvents (methanol, methylene chloride/formic acid, and methanol/formic acid) were compared. All of the isolates tested produced ochratoxin A in one or both culture media after 7 or 14 days of incubation. Based on the results obtained, the use of both culture media is recommended. As extraction solvent, either methanol or methanol-formic acid could be used. This method also provides quantitative information on the level of ochratoxin produced by the cultures. The simplicity of the method makes it very useful when many fungal isolates need to be screened.
The effects of pu-erh tea, which is prepared by fermentation of tea, on oxidative damage and nitric oxide scavenging, compared with various other brands of tea were investigated. The total antioxidant activity was determined using the Trolox equivalent antioxidant capacity (TEAC) assay. The results showed that TEAC values of the 200 microg/mL water extracts of pu-erh tea (WEPT), green tea, oolong tea, and black tea were 86.3, 85.3, 87.4, and 80.3 (microg/mL), respectively, indicating that WEPT showed a significant antioxidant activity. WEPT, like green tea extract, oolong tea extract, and black tea extract, exhibited a remarkable protective effect in lipid (liposome) and nonlipid (protein and deoxyribose) model systems, implying that it is an inhibitor of lipid and nonlipid oxidative damage. It also exhibited metal-binding ability, reducing power, and scavenging effect for free radicals. Moreover, WEPT showed a decreasing effect on nitric oxide production of lipopolysaccharide-induced RAW 264.7 macrophages. In addition, the results revealed that epicatechin (EC), flavonoid, ascorbic acid, and polyphenolic compounds are present in WEPT, which may partially account for the protective effect on oxidative damage. Thus, WEPT may have potential as an antioxidant and as a nitric oxide scavenging agent.
The four major commercial teas, oolong, black, pu-erh, and green teas, have been manufactured in southeast Asia. In this study, we evaluated the growth suppressive and hypolipidemic effect of these four different tea leaves by oral feeding to male Sprague-Dawley rats for 30 weeks. The results showed that the suppression of body weights of tea leaves-fed groups were in the order: oolong tea > pu-erh tea > black tea > green tea. Pu-erh tea and oolong tea could lower the levels of triglyceride more significantly than that of green tea and black tea, but pu-erh tea and green tea were more efficient than oolong tea and black tea in lowering the level of total cholesterol. In lipoprotein, 4% pu-erh tea could increase the level of HDL-C and decrease the level of LDL-C, but other teas simply decrease the levels of both. The activity of antioxidant enzyme SOD is increased in all tea-fed groups as compared to the basal diet-fed group. Finally, relative weight ratios of liver to epididylmal adipose tissue were lower in feeding oolong tea and pu-erh tea groups. On the basis of these findings, it seemed that the fully fermented pu-erh and black tea leaves and partially fermented oolong tea leaves were more effective on their growth suppressive and hypolipidemic effects as compared to the nonfermented green tea leaves.
Conversions of statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, from lactone forms to their corresponding hydroxy acid form in 0.1 N NaOH or 0.05 N KOH (prepared with 25, 50, 75, 90% acetonitrile or methanol in water or 100% water) were evaluated. Results showed that lactone form statins could be transformed almost completely only in alkaline solutions prepared with 25 or 50% acetonitrile. In all methanolic alkaline solutions, lactone form statins could also be converted entirely, nevertheless, they would be further transformed to the methyl ester of the hydroxy acid form and the transformation increased as methanol rises. When lactone and hydroxy acid forms of statins were in methanol, ethyl acetate, 70% acetonitrile in water (with 0.5% acetic acid or no) for 0-48 h at room temperature or in 100 degrees C water for 0-2 h, lactone form statins were converted to their corresponding hydroxy acids, which were raised as time extends and the highest conversions of them were about 35% in 100 degrees C water and 70% acetonitrile, slightly transformed for lactone form statins in 70% acetonitrile (with 0.5% acetic acid) after 8 h, and the other treatments for all statins showed no significant changes. Interferences would be reduced efficiently when statins were extracted from Pu-Erh tea with methanol, ethyl acetate or 100 degrees C water followed by purifying through a C18 solid-phase extraction cartridge. Lovastatin was the only statin found in Pu-Erh tea and the highest content of it was found under ethyl acetate extraction. In ethyl acetate and methanol extracts, lovastatin existed merely as lactone form. The lowest content of lovastatin was found in the 100 degrees C water extract of Pu-Erh tea, however, both of lactone and hydroxy acid forms were found to exist in the extract.
Fatty acid synthase (FAS) is a key enzyme of lipogenesis. Overexpression of FAS is dominant in cancer cells and proliferative tissues. The expression of FAS in the livers of rats fed pu-erh tea leaves was significantly suppressed. The gains in body weight, levels of triacylglycerol, and total cholesterol were also suppressed in the tea-treated rats. FAS expression in hepatoma HepG2 cells was suppressed by the extracts of pu-erh tea at both the protein and mRNA levels. FAS expression in HepG2 cells was strongly inhibited by PI3K inhibitor LY294002 and JNK inhibitor II and slightly inhibited by p38 inhibitor SB203580 and MEK inhibitor PD98059, separately. Based on these findings, we suggest that the suppression of FAS in the livers of rats fed pu-erh tea leaves may occur through downregulation of the PI3K/AKt and JNK signaling pathways. The major components of tea that have been demonstrated to be responsible for the antiobesity and hypolipidemic effects are catechins, caffeine, and theanine. The compositions of catechins, caffeine, and theanine varied dramatically in pu-erh, black, oolong, and green teas. The active principles and molecular mechanisms that exerted these biological effects in pu-erh tea deserve future exploration.
Adlay angkak a new developed product from an adlay substrate fermented by Monascus fungi can be used both as a natural coloring and a dietary supplement. However, not only useful secondary metabolites such as mevinolin and pigments are produced; the fungi also produce toxin substance called citrinin. This study conducted the cultivation of M. purpureus (ATCC 16365, BCC 6131, DMKU and FTCMU) and M. ruber TISTR 3006 on the adlay substrate for mevinolin, citrinin, pigments and glucosamine synthesis at room temperature (32-35 degrees C) for 28 days. The results elucidated that glucosamine levels expressed as the mold growth in solid-state fermentation corresponded as a relatively reliable indicator to the mevinolin, citrinin and pigments production. M. purpureus DMKU produced the lowest citrinin content of 0.26 ppm and the highest mevinolin content of 25.03 ppm with pigment concentrations expressed by absorbance at wavelengths of 400, 470 and 500 nm for yellow, orange and red pigments of 9.76, 3.03 and 3.43 units respectively and moisture content and pH of 83.51% and 6.54 respectively. This study suggested that M. purpureus DMKU has a potential for the production of adlay angkak within an authorized citrinin level.