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The synthetic compound NO-1886 is a lipoprotein lipase activator that has been proven to be highly effective in lowering plasma triglycerides and elevating high-density lipoprotein cholesterol. Recently, we found that NO-1886 also had a plasma glucose-reducing action in high-fat/high-sucrose diet-induced diabetic rabbits. In the current study, we investigated the effects of NO-1886 on the morphology of adipocytes, plasma levels of tumor necrosis factor-α (TNF-α) and free fatty acids (FFA) in miniature pigs fed a high-fat/high-sucrose diet. Our results showed that feeding a high-fat/high-sucrose diet to miniature pigs increased the size of adipocytes, and the plasma levels of TNF-α, FFA, and glucose. This diet also induced insulin resistance and impaired the acute insulin response to glucose loading. Supplementing 1% NO-1886 to the high-fat/high-sucrose diet inhibited adipocyte enlargement, and suppressed plasma levels of TNF-α, FFA, and glucose. The decrease in plasma TNF-α and FFA was simultaneous with the decrease in plasma glucose. We also found an increased whole body glucose clearance and an increased acute insulin response to intravenous glucose loading by NO-1886 supplementation. These data suggest that NO-1886 improves the glucose metabolism in high-fat/high-sucrose diet-induced diabetic minipigs by decreasing fat deposit, and suppressing plasma TNF-α and FFA levels. Therefore, NO-1886 is potentially beneficial for the treatment of insulin-resistant syndrome. [Copyright &y& Elsevier]

Background: Depression is a recurrent and devastating mental disease that is highly prevalent worldwide. Prolonged exposure to stressful events or a stressful environment is detrimental to mental health. In recent years, an inflammatory hypothesis has been implicated in the pathogenesis of stress-induced depression. However, less attention has been given to the initial phases, when a series of stress reactions and immune responses are initiated. Peripheral CD4+ T cells have been reported as the major contributors to the occurrence of mental disorders. Chronic stress exposure-evoked release of cytokines can promote the differentiation of peripheral CD4+ cells into various phenotypes. Among them, Th17 cells have attracted much attention due to their high pathogenic potential in central nervous system (CNS) diseases. Thus, we intended to determine the crucial role of CD4+ Th17 cells in the development of specific subtypes of depression and unravel the underpinnings of their pathogenetic effect.Methods: In the present research, a daily 6-h restraint stress paradigm was employed in rats for 28 successive days to mimic the repeated mild and predictable, but inevitable environmental stress in our daily lives. Then, depressive-like symptoms, brain-blood barrier (BBB) permeability, neuroinflammation, and the differentiation and functional changes of CD4+ cells were investigated.Results: We noticed that restrained rats showed significant depressive-like symptoms, concomitant BBB disruption and neuroinflammation in the dorsal striatum (DS). We further observed a time-dependent increase in thymus- and spleen-derived naïve CD4+ T cells, as well as the aggregation of inflammatory Th17 cells in the DS during the period of chronic restraint stress (CRS) exposure. Moreover, increased Th17-derived cytokines in the brain can further impair the BBB integrity, thus allowing more immune cells and cytokines to gain easy access to the CNS. Our findings suggested that, through a complex cascade of events, peripheral immune responses were propagated to the CNS, and gradually exacerbated depressive-like symptoms. Furthermore, inhibiting the differentiation and function of CD4+ T cells with SR1001 in the early stages of CRS exposure ameliorated CRS-induced depressive-like behaviour and the inflammatory response.Conclusions: Our data demonstrated that inflammatory Th17 cells were pivotal in accelerating the onset and exacerbation of depressive symptoms in CRS-exposed rats. This subtype of CD4+ T cells may be a promising therapeutic target for the early treatment of stress-induced depression. [ABSTRACT FROM AUTHOR]

Nowadays, the root of Rose cymosa Tratt. (Rosaceae) is widely used in clinic as one of the sources of Chinese herb medicine Jinyinggen. However, only few studies have been done on its chemical composition and quality control. In this study, 27 monomeric compounds were obtained from the ethanol extract of the roots of R. cymosa Tratt., including two undescribed triterpenes, one of which contains a distinctive contracted five‐membered A‐ring ursane‐type skeleton and the other is a common ursane‐type tritepene. Then, triterpenoids, the main components of the R. cymosa root, were qualitatively and quantitatively analyzed by thin‐layer chromatography and high‐performance liquid chromatography methods. Thin‐layer chromatography can identify seven triterpenoids in R. cymosa Tratt. spontaneously. For the high‐performance liquid chromatography fingerprint, total of 16 chromatographic peaks were selected as the common peaks of 20 batches of samples, ten of which were identified by reference substances. At the same chromatographic condition, five abundant triterpenoids were quantitatively assayed. R. cymose, as one of the origins of Jinyinggen, was similar to R. laevigata in triterpenoids compounds, which demonstrated that both of them could be used in the clinical medication. These work also laid a foundation for the further research and development of triterpenoids in R. cymosa root. [ABSTRACT FROM AUTHOR]

The uptake of modified low-density lipoprotein (LDL) and the accumulation of lipid droplets induce the formation of vascular smooth muscle cells (VSMCs)-derived foam cells, thereby promoting the development and maturation of plaques and accelerating the progression of atherosclerosis. Celastrol is a quinine methide triterpenoid isolated from the root bark of traditional Chinese herb Tripterygium wilfordii. It possesses various biological properties, including anti-obesity, cardiovascular protection, anti-inflammation, etc. In the present study, we found that celastrol significantly reduced lipid accumulation induced by oxidized LDL (ox-LDL) in VSMCs. Mechanistically, celastrol up-regulated adenosine triphosphate-binding cassette transporter A1 (ABCA1) expression through activating liver X receptor α (LXRα) expression, which contributed to inhibit lipid accumulation in VSMCs. Meanwhile, celastrol decreased lipid accumulation by triggering autophagy in VSMCs. Therefore, these findings supported celastrol as a potentially effective agent for the prevention and therapy of atherosclerosis. Image 1 • Celastrol suppresses lipid accumulation by activating LXRα/ABCA1 signaling in VSMCs. • Celastrol inhibits lipid storage by inducing autophagy in VSMCs. • Celastrol is a potentially effective agent for treatment of atherosclerosis. [ABSTRACT FROM AUTHOR]

Prunella vulgaris polysaccharides (PVPs) have a variety of biological activities, but the mechanism and extent of their anti-hyperlipidaemic effect remain unclear. In vitro, PVPs had a significant inhibitory effect on angiotensin (Ang II)-induced vascular smooth muscle cell (VSMC) proliferation. A metabolomics approach based on gas chromatography–mass spectrometry (GC–MS) and chemometrics was established in this study to evaluate the anti-hyperlipidaemic activity of PVPs in a high-fat Sprague-Dawley rat model. In vivo, PVPs could significantly reduce the weight gain and the increases in serum total cholesterol (TC), low-density lipoprotein (LDL)-C and non-high-density lipoprotein (HDL)-C levels observed in rats fed a high-fat diet; they could also significantly increase serum GSH-Px activity, reduce the content of MDA and TNF-α and decrease abdominal fat volume in rats. Furthermore, PVPs exerted a repairing effect on morphological and structural damage in liver tissue cells in hyperlipidaemic rats fed a high-fat diet. PVPs improved lipid metabolism disorder in rats. Alanine, threonine, succinic acid, proline, inositol and arachidonic acid levels in the serum were considered potential biomarkers involved in amino acid, glucose, energy and lipid metabolism. Therefore, PVPs may interfere with hyperlipidaemia through anti-lipid peroxidation effects, attenuation of inflammation and regulation of glucose, amino acid, energy and lipid metabolism. [ABSTRACT FROM AUTHOR]

Overexpression and activation of Axl receptor tyrosine kinase have been widely accepted to promote cell proliferation, chemotherapy resistance, invasion, and metastasis in several human cancers, such as lung, breast, and pancreatic cancers. Axl, a member of the TAM (Tyro3, Axl, Mer) family, and its inhibitors can specifically break the kinase signaling nodes, allowing advanced patients to regain drug sensitivity with improved therapeutic efficacy. Therefore, the research on Axl is promising and it is worthy of further investigations. In this review, we present an update on the Axl inhibitors and provide new insights into their latent application. [ABSTRACT FROM AUTHOR]

Excessive autophagic activity of alveolar type II epithelial (AT-II) cells is one of the main causes of acute lung injury (ALI); however, the underlying molecular mechanism remains to be determined. The microRNAs (miRNAs) are involved with autophagy in many diseases. The objective of this study was therefore to investigate the relationship between the miRNA expression and the autophagic activity of the AT-II cells in the pathogenesis of ALI and its molecular mechanism. A mouse model of ALI and AT-II cell injury was induced using lipopolysaccharide (LPS) in vivo and in vitro, and the expression of miR-34a and the autophagy-related proteins LC3 II/I and p62 were determined. Moreover, the autophagic activity was investigated after miR-34a overexpression and inhibition. The effects of miR-34a on its target gene, FoxO3, in regulating autophagic activity in AT-II cells were also determined. LPS induced autophagic activity and increased the expression of miR-34a in lung tissues and in AT-II cells. The in vitro results showed that the upregulation of miR-34a suppressed, whereas the inhibition of miR-34a promoted, autophagy in AT-II cells. Moreover, miR-34a could directly bind to the 3′-untranslated region of the autophagy-related gene, FoxO3, to decrease its expression. In addition, the knockdown of FoxO3 expression inhibited the autophagic activity in AT-II cells. Together, this study suggested that miR-34a might suppress the excessive autophagic activity in AT-II cells via targeting FoxO3 to reduce the damage of LPS-induced ALI. [ABSTRACT FROM AUTHOR]

Prunella is a genus of perennial herbaceous plants in the Labiatae family. There are approximately 15 species worldwide, distributed widely in the temperate regions and tropical mountains of Europe and Asia. In the genus Prunella , P. vulgaris is the most studied, following a several thousand-year history as a traditional antipyretic and antidotal Chinese herb. Furthermore, since ancient times, P. vulgaris has been widely used as a cool tea ingredient and consumed as a vegetable. The genus Prunella contains triterpenoids and their saponins, phenolic acids, sterols and associated glycosides, flavonoids, organic acids, volatile oil and saccharides. Modern pharmacological studies have revealed that Prunella possess antiviral, antibacterial, anti-inflammatory, immunoregulatory, anti-oxidative, anti-tumor, antihypertensive and hypoglycemic functions. The active components related to these functions are mainly triterpenoids, phenolic acids, flavonoids and polysaccharides. This review mainly summarizes recent advances in traditional usage, chemical components and pharmacological functions. [ABSTRACT FROM AUTHOR]

Prunella vulgaris L. (P. vulgaris , Labiatae) is a perennial medicinal and edible plant widely used in China, Korea, Japan and Europe. The reddish brown spica of P. vulgaris (Prunellae Spica), which is collected in summer, has been commonly used in traditional medicine and food industry, while it is also used with whole grass in Europe and Taiwan. To clarify the regulatory pathways and mechanism of quality formation in P. vulgaris , targeted metabolomic, transcriptomic, and proteomic analyses of Prunellae Spica samples from five consecutive developmental stages were carried out. The results showed that terpenoids were mainly synthesized in the maturity stage of Prunellae Spica, with the key enzymes and coding genes in downstream pathways being mainly expressed during ripening, while related enzymes in the upstream pathway showed the opposite pattern. Flavonoids mainly accumulated before ripening, with highly expressed pathway enzymes and coding genes. The accumulation of phenylpropanoids was relatively active throughout the development process. Rosmarinic acid (RA) and its synthetic intermediate products mainly accumulated via more active pathway enzymes and coding genes before ripening. The regulatory factors and metabolites related to RA synthesis were mainly enriched in phenylpropanoid biosynthesis, plant hormone signal transduction, plant pathogen interaction, oxidative phosphorylation, and endoplasmic reticulum protein processing pathways. [Display omitted] [ABSTRACT FROM AUTHOR]

Curcumin nicotinate (Curtn) is a synthesized ester derivative of curcumin and niacin. Our previous study has shown that Curtn lowers serum low-density lipoprotein cholesterol (LDL-C) levels in apoE−/− mice and promotes LDL-C uptake into HepG2 cells in vitro. The present study was to test the hypothesis that Curtn decreases serum LDL-C levels through decreased expression of pro-protein convertase subtilisin/kexin type 9 (PCSK9) and subsequent increase in LDL receptor expression. Male Wistar rats on high-fat diet (HFD) were treated with Curtn or rosuvastatin. Curtn or rosuvastatin treatment significantly decreased serum levels of total cholesterol (TC) and LDL-C in rats on HFD with increased liver LDL receptor expression. LDL-C-lowering effect of Curtn was not observed in LDL receptor deficient (LDLR−/−) mice on HFD, while rosuvastatin still decreased serum lipid levels in LDLR−/− mice, indicating that the reduction of serum LDL-C levels by Curtn treatment was LDL receptor-dependent. Curtn treatment also significantly decreased the protein expression of PCSK9 in Wistar rats and LDLR−/− mice. In HepG2 cells with overexpression of human PCSK9, Curtn treatment significantly increased LDL-C uptakes into hepatocytes, and increased LDL receptor distribution on cell surface in association with decreased PCSK9 protein expression. RNAi-LDLR significantly attenuated the effect of Curtn on LDLR distribution on cell surface. These data indicates that Curtn would decrease serum LDL-C level at least partially through inhibition of PCSK9 expression, and subsequent increase in LDL receptor expression and distribution in hepatocytes, serving as a potential novel compound to treat hyperlipidemia. [ABSTRACT FROM AUTHOR]

The classical traditional Chinese formulation LiuweiDihuang, shown to have clinical efficacy for 'nourishing kidney-yin' in traditional Chinese medicine, has been used for thousands of years in China. Little attention, however, has been paid to quality control methods for this formulation. Hence, a rapid and sensitive analytical technique is urgently needed for the evaluation of LiuweiDihuang preparations to assess its quality and pharmacological functionality. In this study, an ultra high performance liquid chromatography dual-wavelength method was developed to simultaneously determine 11 constituents in LiuweiDihuang preparations. This robust approach provided a fast and comprehensive quantitative determination of the major bioactive markers within LiuweiDihuang preparations. To distinguish four dosage forms of LiuweiDihuang preparations, a random forest technique was applied on the spectrometric fingerprint data obtained. This combination approach of chromatographic techniques and data analyses might serve as a rapid and efficient tool to ensure the quality of LiuweiDihuang preparations and other Chinese medicinal formulations and can support quality control and scientific research into the pharmacological potential for these formulations. [ABSTRACT FROM AUTHOR]

An investigation of Hedyotis corymbosa resulted in the isolation of eighteen compounds, including six iridoids ( 1 – 6 ), six monocyclic phenols ( 7 – 12 ), one triterpene ( 13 ), two sterols ( 14 – 15 ), one anthranquinone ( 16 ), one oxylipin ( 17 ) and one coumarin ( 18 ). The compounds were identified as scandoside methyl ester ( 1 ), deacetyl asperulosidic acid ( 2 ), deacetyl asperulosidic acid methyl ester ( 3 ), daphylloside ( 4 ), 10- O -benzoyl deacetyl asperulosidic acid methyl ester ( 5 ), 10- O -benzoyl scandoside methyl ester ( 6 ), p -hydroxybenzaldehyde ( 7 ), 4-methoxybenzene-1,2-diol ( 8 ), Z - p -hydroxyphenylacetyl ( 9 ), p -hydroxybenzoic acid ( 10 ), E - p -hydroxyphenylacetyl ( 11 ), protocatechuic acid ( 12 ), oleanic acid ( 13 ), daucosterol ( 14 ), β -sitosterol ( 15 ), 1-methoxy-2-hydroxyanthraquinone ( 16 ), (9R*,10S*,7E)-6,9,10-trihydroxyocta- dec-7-enoic acid ( 17 ) and hedyotiscone A ( 18 ). Compounds 4 , 7 – 9 , 11 and 17 were isolated from H . corymbosa for the first time, compound 8 was a new natural product. The chemotaxonomic significance of these compounds was summarized in the paper. The presence of (9R*,10S*,7E)-6,9,10-trihydroxyoctadec-7-enoic acid ( 17 ) in H . corymbosa could be used to differentiate it from Hedyotis diffusa . Compounds with a 10- O -benzoyl structure, such as compounds 5 and 6 , could be used as typical components for quality control. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are highly conserved, small, noncoding RNAs that regulate gene expression at the posttranscriptional level. Their actions affect numerous important biological processes, including adipocyte differentiation and function, sugar and lipid metabolism, and insulin production and secretion. Recent reports suggest miRNAs may also be involved in the pathogenic processes of obesity, diabetes, and insulin resistance. In this review, we summarize research progresses on adipocyte miRNAs and their physiological and pathological implications. [ABSTRACT FROM AUTHOR]

The idiosyncratic hepatotoxicity of Polygonum multiflorum Thunb. (PM) has attracted great interest, and tetrahydroxy stilbene glucoside (TSG) was the main idiosyncratic hepatotoxicity constituent, but biological detoxification on idiosyncratic hepatotoxicity of PM was not well investigated. This study aimed to illustrate biological detoxification mechanism on PM-induced idiosyncratic hepatotoxicity by Ganoderma lucidum (G. lucidum). G. lucidum was used for biological detoxification of tetrahydroxy stilbene glucoside (TSG)-induced idiosyncratic hepatotoxicity of PM. The TSG consumption and products formation were dynamically determined during transformation using high-performance liquid chromatography coupled with diode-array detection and electrospray ionization tandem mass spectrometry (HPLC-DAD-MSn). The transformation invertases (β -D-glucosidase and lignin peroxidase) were evaluated by using intracellular and extracellular distribution and activity assay. The key functions of lignin peroxidase (LiP) were studied by experiments of adding inhibitors and agonists. The entire TSG transformation process was confirmed in vitro simulated test. The cellular toxicity of TSG and the transformation products was detected by MTT. A suitable biotransformation system of TSG was established with G. lucidum , then p -hydroxybenzaldehyde and 2,3,5-trihydroxybenzaldehyde can be found as transformation products of TSG. The transformation mechanism involves two extracellular enzymes, β -D-glucosidase and LiP. β -D-glucosidase can remove glycosylation of TSG firstly and then LiP can break the double bond of remaining glycosides. The toxicity of TSG after biotransformation by G. lucidum was attenuated. This study would reveal a novel biological detoxification method for PM and explain degradation processes of TSG by enzymic methods. [Display omitted] • The idiosyncratic hepatotoxicity of Polygonum multiflorum Thunb. has attracted great interest. • Ganoderma lucidum can used for biological detoxification of tetrahydroxy stilbene glucoside (TSG) of Polygonum multiflorum. • TSG first formed TSG aglycone, and then formed p -hydroxybenzaldehyde and 2,3,5-trihydroxybenzaldehyde. • β -D-glucosidase can remove glycosylation of TSG firstly and then LiP can break the double bond of remaining glycosides. • The cellular toxicity of TSG was attenuated after biotransformation in vitro. [ABSTRACT FROM AUTHOR]

Abstract: Evidences indicate that a complex relationship exists among sleep disorders, obesity and insulin resistance. NEU-P11 is a novel melatonin agonist used in treatment of psychophysiological insomnia, and in animal studies NEU-P11 showed sleep-promoting effect. In this study, we applied NEU-P11 on obese rats to assess its potential melatoninergic effects in vivo. Obese models were established using high-fat/high-sucrose-fed for 5 months. NEU-P11 (10mg/kg)/melatonin (4mg/kg)/vehicle were administered by a daily intraperitoneal injection respectively for 8 weeks. Our results showed that NEU-P11 or melatonin inhibited both body weight gain and deposit of abdominal fat with no influence on food intake. The impaired insulin sensitivity and antioxidative potency were improved and the levels of plasma glucose, total cholesterol (TC), triglycerides (TG) decreased with an increased in HDL-cholesterol (HDL-c) after NEU-P11 or melatonin administration. These data suggest that NEU-P11, like melatonin, decreased body weight gain and improved insulin sensitivity and metabolic profiles in obese rats. We conclude that NEU-P11 has a melatoninergic effect on regulating body weight in obese rats and also improving metabolic profiles and efficiently enhancing insulin sensitivity. [Copyright &y& Elsevier]

Abstract: Inflammation, closely associated with obesity, is emerging as an important risk factor for the pathophysiological development of atherosclerosis and diabetes mellitus. Fat balance is critical in the aetiology of obesity. Lipoprotein lipase is an important enzyme in lipid metabolism. The aim of this study was to investigate the long-term effect of the lipoprotein lipase activator, NO-1886, on inflammation cytokines, adiposity and related diseases in miniature pigs fed a high-fat/high-sucrose/high-cholesterol diet (HFSC diet). Chinese Bama-miniature pigs were fed a control diet or HFSC diet with or without NO-1886 for 5 months. The levels of inflammation-associated cytokines were determined using the antibody arrays. Feeding of the HFSC diet to miniature pigs markedly increased the expression of inflammatory cytokines. On the other hand, supplementation of NO-1886 to HFSC diet decreased the expression of inflammatory cytokines significantly, protecting against the development of atherosclerosis and diabetes mellitus. NO-1886 may have a beneficial effect on the most inflammation-associated cytokines, and this effect may contribute to improving atherosclerosis and diabetes mellitus. [Copyright &y& Elsevier]

Prunella vulgaris L., better known as 'self-heal', has been extensively used in the traditional system of medicines. To reveal the regulatory mechanism of its development, TMT-based quantitative proteome analysis was performed in the Prunella vulgaris L. spica before and during ripening (Group A and Group B, respectively). This analysis resulted in the identification of 7655 proteins, of which 1910 showed differential abundance between the two groups. Pronounced changes in the proteomic profile included the following: 1) Stress-responsive proteins involved in protecting cells and promoting fruit ripening and seed development were highly abundant during ripening. 2) The degradation of chlorophyll, inhibition of chlorophyll biosynthesis and increased abundance of transketolase occurred simultaneously in the spica of Prunella vulgaris L., resulting in the spica changing color from green to brownish red. 3) The abundance of protein species related to phenylpropanoid biosynthesis mainly increased during ripening, while flavonoid and terpenoid backbone biosynthesis mostly occurred before ripening. This study establishes a link between protein profiles and mature phenotypes, which will help to improve our understanding of the molecular mechanisms involved in the maturation of Prunella vulgaris L. at the proteome level and reveal the scientific connotation for the best time to harvest Prunella vulgaris L. This work provides a scientific basis for the production of high-quality medicinal Prunella vulgaris L., as well as a typical demonstration of molecular research used for the harvest period of traditional Chinese medicine. This work provided a comprehensive overview on the functional protein profile changes of Prunella vulgaris L. spica at different growing stages, as well as the scientific rationale of Prunella vulgaris L. harvested in summer after brownish red, thus laid an intriguing stepping stone for elucidating the molecular mechanisms of quality development. Unlabelled Image • Prunella vulgaris L. spica was sampled at five developmental stages (from heading to physiological maturity). • LC-MS matched 7655 proteins, of which 6405 can be quantified and 1910 proteins showed differences in abundance. • High abundance of stress-responsive protein species involved in fruit maturity and seed development during spica ripening. • The up-representation of transketolase, the degradation and inhibition synthesis of chlorophyll cause the spica changing color. • Increased levels of protein related to phenylpropanoid biosynthesis were observed during spica ripening [ABSTRACT FROM AUTHOR]

Abstract: A new steroid, 3β, 16α-dihydroxy-(5α)-cholestan-21-oic acid , was isolated from the aerial parts of Selaginella pulvinata. Its structure was elucidated on the basis of spectral analysis. [Copyright &y& Elsevier]

Review: 70 refs. [ABSTRACT FROM AUTHOR]