Natural bioactive constituents from herbs and nutraceuticals promote browning of white adipose tissue.

Obesity is a significant public health problem worldwide that is characterized by abnormal or excessive fat accumulation. Unfortunately, the application of available weight-loss drugs has been restricted because of their serious adverse effects. Browning of white adipose tissue (WAT), which refers to the transformation of white adipocytes to beige adipocytes under certain stimulations, is regarded as a new strategy to solve the obesity problem. Numerous studies have recently evidenced that traditional Chinese medicine (TCM) could promote browning of WAT with multi-component and multi-target characteristics. This article summarizes natural constituents from TCM with stimulatory effects on browning of WAT in the past two decades. The active ingredients can be generally divided into polyphenols, saponins, alkaloids, terpenoids, phenylpropanoids and others, such as resveratrol, quercetin, curcumin, genistein, capsaicin, epigallocatechin gallate (EGCG), berberine, menthol, emodin and ginsenosides. Simultaneously, the chemical structures, source, model, efficacy and mechanism of these monomeric compounds are also described. And the mechanisms of these active ingredients are mainly involved in the regulation of PRDM16, PGC-1α, PPARγ, SIRT1, AMPK, ß3-adrenergic receptors, TRPV1 and TRPM8 channels, FGF21 and miRNAs. The present article opens opportunities for developing novel drugs or supplements from TCM with wide acceptability to prevent obesity progression and its associated metabolic disorders.

Study on the correlation between homocysteine-related dietary patterns and gestational diabetes mellitus:a reduced-rank regression analysis study.

BACKGROUND: This study aimed to evaluate the association between homocysteine-related dietary patterns and gestational diabetes mellitus. METHODS: A total of 488 pregnant women at 24-28 weeks of gestation between January 2019 and December 2020 were included. Demographic characteristics, dietary intake, and multivitamin supplement intake information were collected using a food frequency questionnaire (FFQ); fasting venous blood samples were collected for serum index detection. Serum homocysteine (Hcy), folic acid, and B12 were selected as response variables, and hyperhomocysteinemia (hHcy)-related dietary patterns were extracted using the reduced rank regression.. The relationship between the score of hHcy-related dietary patterns and GDM was analyzed using a multivariate logistic regression model. RESULTS: Three hHcy-related dietary patterns were extracted. Only mode 2 had a positive and significant relationship with the risk of developing GDM. After adjusting for confounding factors, the risk of GDM was significantly increased in the highest quartile array compared with the lowest quartile of the pattern (OR = 2.96, 95% Confidence Interval: 0.939-9.356, P = 0.004). There was no significant correlation between dietary pattern 1 and GDM risk (P > 0.05). CONCLUSIONS: Homocysteine-related dietary patterns were positively associated with gestational diabetes mellitus. Adjusting dietary patterns may contribute to the intervention and prevention of GDM.

Glycoside constituents with various antioxidant effects from fresh Cynomorium songaricum.

Cynomorium songaricum Rupr. (CSR), an edible and medicinal material, is widely cultivated in desert regions of Eastern and Western Asia, Europe, and North Africa. Ten glycoside constituents 1-10 including one new songaricumone A (1) were isolated from the fresh C. songaricum. Their structures were elucidated by comprehensive NMR data analysis. Further, various antioxidant effects of isolated compounds (1-3 and 5-10) were comprehensively and comparatively investigated. In conclusion, it is obvious that different glycosides vary significantly toward different sources of free radicals, which are attributed to different aglycones and substituted positions of sugar unit in structures.

Antidepressant active ingredients from herbs and nutraceuticals used in TCM: pharmacological mechanisms and prospects for drug discovery.

Depression is a widespread psychological disorder that affects up to 20% of the world's population. Traditional Chinese medicine (TCM), with its unique curative effect in depression treatment, is gaining increasing attention as the discovery of novel antidepressant drug has become the pursuit of pharmaceutical. This article summarizes the work done on the natural products from TCM that have been reported to conceive antidepressant effects in the past two decades, which can be classified according to various mechanisms including increasing synaptic concentrations of monoamines, alleviating the hypothalamic-pituitary-adrenal (HPA) axis dysfunctions, lightening the impairment of neuroplasticity, fighting towards immune and inflammatory dysregulation. The antidepressant active ingredients identified can be generally divided into saponins, flavonoids, alkaloids, polysaccharides and others. Albiflorin, Baicalein, Berberine chloride, beta-Asarone, cannabidiol, Curcumin, Daidzein, Echinocystic acid (EA), Emodin, Ferulic acid, Gastrodin, Genistein, Ginsenoside Rb1, Ginsenoside Rg1, Ginsenoside Rg3, Hederagenin, Hesperidin, Honokiol, Hyperoside, Icariin, Isoliquiritin, Kaempferol, Liquiritin, L-theanine, Magnolol, Paeoniflorin, Piperine, Proanthocyanidin, Puerarin, Quercetin, Resveratrol (trans), Rosmarinic acid, Saikosaponin A, Senegenin, Tetrahydroxystilbene glucoside and Vanillic acid are Specified in this review. Simultaneously, chemical structures of the active ingredients with antidepressant activities are listed and their sources, models, efficacy and mechanisms are described. Chinese compound prescription and extracts that exert antidepressant effects are also introduced, which may serve as a source of inspiration for further development. In the view of present study, the antidepressant effect of certain TCMs are affirmative and encouraging. However, there are a lot of work needs to be done to evaluate the exact therapeutic effects and mechanisms of those active ingredients, specifically, to establish a unified standard for diagnosis and evaluation of curative effect.

Citrus aurantium L. var. amara Engl. inhibited lipid accumulation in 3T3-L1 cells and Caenorhabditis elegans and prevented obesity in high-fat diet-fed mice.

Natural products with anti-obesity effects and few side effects have attracted great attention recently. Citrus aurantium L. var. amara Engl. (CAVA) is popularly consumed as an edible and medicinal resource in China. However, its anti-obesity effects were poorly understood. The anti-obesity effects of CAVA extracts were systematically evaluated using 3T3-L1 cells, Caenorhabditis elegans (C. elegans) and high fat diet (HFD)-fed mice. Flavonoid-rich (EA) extracts with neohesperidin, hesperidin and naringin comprising 32.15%, were isolated from CAVA. EA extracts treatment significantly inhibited differentiation of 3T3-L1 preadipocytes by modulating lipid metabolism-related mediators. EA extracts supplementation also inhibited antioxidant responses in C. elegans by decreasing reactive oxygen species generation and malonaldehyde value, and increasing superoxide dismutase content. EA extracts feeding markedly decreased triglyceride (TG) content, and affected expression of genes involved in lipid and glucose metabolism in wild type C. elegans. TG content in mdt-15 (XA7702) mutants was not decreased by EA extracts administration, suggesting that EA extracts treatment might inhibit lipid accumulation in C. elegans dependent on mdt-15. EA extracts intervention further reduced body weight gain and modulated plasma biochemical parameters in HFD-fed mice. EA extracts treatment prevented HFD-induced epididymal adipose hypertrophy, liver oxidative injuries and steatosis. EA extracts administration also strongly prevented HFD-induced reduction of gut microbial diversity, decreased the Firmicutes-to-Bacteroidetes ratio and the Erysipelotrichaceae abundance, and enhanced the Bifidobacteriace abundance in HFD-fed mice. EA extracts from blossoms of CAVA were excellent antiobesogenic candidates that acted through multiple mechanisms that acted simultaneously.

Live births resulting from 0PN-derived embryos in conventional IVF cycles.

PURPOSE: The aim of this study was to (1) investigate the incidence of embryos derived from "unfertilized oocytes" i.e., oocytes not displaying pronuclei (0PN) at the time of the fertilization check and (2) determine the clinical pregnancy rates when transferring 0PN-derived embryos. METHODS: In this retrospective study, 4424 IVF-ET cycles were reviewed. RESULTS: In total, 11.3% (4966/43,949) 0PN-derived embryos were observed. It was found that female age, number of oocytes, and the top-quality embryo rate were significantly correlated with 0PN-derived embryo occurrence. The source of embryos transferred did not impact significantly on clinical pregnancy and live-birth rates. Of the 183 cycles included in this study where 275 0PN-derived embryos were transferred in total, only 0PN-derived embryos were available in 70 of those cycles. It was noteworthy that 13 healthy infants resulted from 0PN-derived embryos with an implantation rate of 17.0%. CONCLUSION: These results indicate that the traditional method of excluding embryos because of those oocytes originally lacking any sign of a pronucleus at the fertilization check should be re-considered as transferring 0PN-derived embryos with subsequent expected developmental performance may be considered as an option for those patients where no other embryos are available.

Sedative and hypnotic effects of the saponins from a traditional edible plant Liriope spicata Lour. in PCPA-induced insomnia mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Liriope spicata Lour., a species listed in the catalogue of 'Medicinal and Edible Homologous Species', is traditionally used for the treatment of fatigue, restlessness, insomnia and constipation. AIM OF THE STUDY: This study is aimed to evaluate the sedative and hypnotic effect of the saponins from a natural plant L. spicata Lour. in vivo. MATERIALS AND METHODS: The total saponin (LSTS) and purified saponin (LSPS) were extracted from L. spicata, followed by a thorough analysis of their major components using the HPLC-MS. Subsequently, the therapeutic efficacy of LSTS and LSPS was evaluated by the improvement of anxiety and depression behaviors of the PCPA-induced mice. RESULTS: LSTS and LSPS exhibited similar saponin compositions but differ in their composition ratios, with liriopesides-type saponins accounting for a larger proportion in LSTS. Studies demonstrated that both LSTS and LSPS can extend sleep duration and immobility time, while reducing sleep latency in PCPA-induced mice. However, there was no significant difference in weight change among the various mice groups. Elisa results indicated that the LSTS and LSPS could decrease levels of NE, DA, IL-6, and elevate the levels of 5-HT, NO, PGD2 and TNF-α in mice plasma. LSTS enhanced the expression of neurotransmitter receptors, while LSPS exhibited a more pronounced effect in regulating the expression of inflammatory factors. In conclusion, the saponins derived from L. spicata might hold promise as ingredients for developing health foods with sedative and hypnotic effects, potentially related to the modulation of serotonergic and GABAAergic neuron expression, as well as immunomodulatory process.

Sedative and hypnotic effects of Polygala tenuifolia willd. saponins on insomnia mice and their targets.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygala tenuifolia Willd. has been widely used in the treatment of cancer, forgetfulness, depression and other diseases. AIM OF REVIEW: The purpose of this study was to investigate the sleep-enhancing effect and mechanism of P. tenuifolia saponins (PTS). MATERIALS AND METHODS: The total saponin (YZ-I) and purified saponin (YZ-II) fractions were extracted and ICR mice model of insomnia was established by p-chlorophenylalanine (PCPA) induction to observe anxiety and depression behaviors. Effects of YZ-I and YZ-II on the levels of neurotransmitters, hormones, and inflammation cytokines were detected by ELISA, RT-qPCR and western blotting. RESULTS: The results showed that YZ-I and YZ-II reduced the immobility time of mice and prolonged the sleep time of mice and significantly increased the concentrations of 5-HT, NE, PGD2, IL-1ß and TNF-α. YZ-I and YZ-II regulated GABAARα2, GABAARα3, GAD65/67, 5-HT1A and 5-HT2A, while regulated the levels of inflammatory cytokines such as DPR, PGD2, iNOS and TNF-α to exert sedative and hypnotic effects. CONCLUSION: PTS are mainly achieved sedative and hypnotic effects by altering serotonergic, GABAergic and immune systems, but the effects and mechanisms of action of YZ-I were different from YZ-II.

Comparative Activities of Three Compounds from Citrus aurantium L. var. amara Engl. to Improve Oxidized Low-Density Lipoprotein-Induced Lipid Deposition.

The active ingredients of Citrus aurantium have been shown to possess a variety of biological activities, especially anti-inflammatory effects. However, its antiatherosclerotic effects need to be further investigated. The aim of this study is to identify compounds with antiatherosclerotic effects from C. aurantium and to further investigate their mechanisms. Three compounds were separated, and then their antiatherosclerotic effect on foam cells induced by oxidized low-density lipoprotein (ox-LDL) was screened by oil red O staining, BODIPY staining, and Dil-ox-LDL uptake measurement. Cholesterol uptake, cholesterol efflux, RT-PCR, and Western blot analysis were used to comprehensively and comparatively explore the potential mechanisms. Nobiletin (NOB), caffeine (CAF), and naringin (NARG), which were separated from C. aurantium, mainly inhibit the formation of foam cells in different ways. NOB reduced cholesterol uptake and enhanced cholesterol efflux and mainly regulated the expressions of ABCA1, ABCG1, and SRA1. CAF promoted cholesterol efflux, mainly by stimulating the expressions of ABCA1 and ABCG1. NARG was more effective in reducing the expression of SRA1 and CD36, which indicated that NARG mainly prevented atherosclerosis by blocking cholesterol uptake. The above results show in detail the antiatherosclerotic activity and mechanism of these compounds, making contributions to their potential applications.

Chemical Composition and Antibacterial and Antiulcerative Colitis Activities of Essential Oil from Pruni Semen.

This study was sought to investigate the chemical composition and antibacterial and antiulcerative colitis (UC) effects of essential oil from Pruni Semen (PSEO). A GC-MS assay showed that the major compounds in PSEO were products of amygdalin hydrolysis, which possessed great antibacterial and anti-inflammatory potential. In vitro antibacterial experiments demonstrated that PSEO treatment inhibited activity of four kinds of intestinal pathogens probably by disrupting the cell wall. Further in vivo studies showed that PSEO administration significantly improved physiological indexes, attenuated histopathological characteristics, and inhibited proinflammatory cytokine production in dextran sulfate sodium (DSS)-induced UC mice. Network pharmacology and molecular docking results predicted that PSEO might prevent UC via regulating the PI3K/AKT pathway. Western blotting and immunofluorescence assays were further conducted for verification, and the results evidenced that PSEO intervention significantly regulated the PI3K/AKT pathway and the expression of its downstream proteins in DSS-induced mice. PSEO might provide a new dietary strategy for UC treatment.

Flavonoid extracts of Citrus aurantium L. var. amara Engl. Promote browning of white adipose tissue in high-fat diet-induced mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Obesity has become a public burden worldwide due to its booming incidence and various complications, and browning of white adipose tissue (WAT) is recognized as a hopeful strategy to combat it. Blossom of Citrus aurantium L. var. amara Engl. (CAVA) is a popular folk medicine and dietary supplement used for relieving dyspepsia, which is recorded in the Chinese Materia Medica. Our previous study showed that blossom of CAVA had anti-obesity potential, while its role in browning of WAT was still unclear. AIM OF THE STUDY: This study aimed to characterize the constituents in flavonoids from blossom of CAVA (CAVAF) and to clarify the anti-obesity capacities especially the effects on browning of WAT. MATERIALS AND METHODS: Gradient ethanol eluents from blossom of CAVA were obtained by AB-8 macroporous resin. 3T3-L1 cells and pancreatic lipase inhibition assay were employed to investigate the potential anti-obesity effects in vitro. HPLC and UPLC/MS assays were performed to characterize the chemical profiles of different eluents. Network pharmacology and molecular docking assays were used to reveal potential anti-obesity targets. Furthermore, high-fat diet (HFD)-induced mice were constructed to explore the anti-obesity actions and mechanisms in vivo. RESULTS: 30% ethanol eluents with high flavonoid content and great inhibition on proliferation of 3T3-L1 preadipocytes and pancreatic lipase activity were regarded as CAVAF. 19 compounds were identified in CAVAF. Network pharmacology analysis demonstrated that AMPK and PPARα were potential targets for CAVAF in alleviating obesity. Animal studies demonstrated that CAVAF intervention significantly decreased the body weight, WAT weight, serum TG, TC and LDL-C levels in HFD-fed obese mice. HFD-induced insulin resistance and morphological changes in WAT and brown adipose tissue were also markedly attenuated by CAVAF treatment. CAVAF supplementation potently inhibited iWAT inflammation by regulating IL-6, IL-1ß, TNF-α and IL-10 mRNA expression in iWAT of mice. Furthermore, the gene expression levels of thermogenic markers including Cyto C, ATP synthesis, Cidea, Cox8b and especially UCP1 in iWAT of mice were significantly up-regulated by CAVAF administration. CAVAF intervention also markedly increased the expression levels of PRDM16, PGC-1α, SIRT1, AMPK-α1, PPARα and PPARγ mRNA in iWAT of mice. CONCLUSION: CAVAF treatment significantly promoted browning of WAT in HFD-fed mice. These results suggested that flavonoid extracts from blossom of CAVA were probably promising candidates for the treatment of obesity.

Antioxidant, Antimicrobial, and Anti-Inflammatory Effects of Liriodendron chinense Leaves.

Liriodendron chinense has been widely utilized in traditional Chinese medicine to treat dispelling wind and dampness and used for alleviating cough and diminishing inflammation. However, the antioxidant, antimicrobial, and anti-inflammatory effects of L. chinense leaves and the key active constituents remained elusive. So, we conducted some experiments to support the application of L. chinense in traditional Chinese medicine by investigating the antioxidant, antibacterial, and anti-inflammatory abilities, and to identify the potential key constituents responsible for the activities. The ethanol extract of L. chinense leaves (LCLE) was isolated and extracted, and assays measuring ferric reducing antioxidant power, total reducing power, DPPH•, ABTS•+, and •OH were used to assess its in vitro antioxidant capacities. Antimicrobial activities of LCLE were investigated by minimal inhibitory levels, minimum antibacterial concentrations, disc diffusion test, and scanning electron microscope examination. Further, in vivo experiments including macro indicators examination, histopathological examination, and biochemical parameters measurement were conducted to investigate the effects of LCLE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. LCLE was further isolated and purified through column chromatography, and LPS-induced RAW264.7 cells were constructed to assess the diminished inflammation potential of the identified chemical composites. ABTS•+ and •OH radicals were extensively neutralized by the LCLE treatment. LCLE administration also presented broad-spectrum antimicrobial properties, especially against Staphylococcus epidermidis by disrupting cell walls. LPS-induced ALI in mice was significantly ameliorated by LCLE intervention, as evidenced by the histological changes in the lung and liver tissues as well as the reductions of nitric oxide (NO), TNF-α, and IL-6 production. Furthermore, three novel compounds including fragransin B2, liriodendritol, and rhamnocitrin were isolated, purified, and identified from LCLE. These three compounds exhibited differential regulation on NO accumulation and IL-10, IL-1ß, IL-6, TNF-α, COX-2, and iNOS mRNA expression in RAW264.7 cells induced by LPS. Fragransin B2 was more effective in inhibiting TNF-α mRNA expression, while rhamnocitrin was more powerful in inhibiting IL-6 mRNA expression. LCLE had significant antioxidant, antimicrobial, and anti-inflammatory effects. Fragransin B2, liriodendritol, and rhamnocitrin were probably key active constituents of LCLE, which might act synergistically to treat inflammatory-related disorders. This study provided a valuable view of the healing potential of L. chinense leaves in curing inflammatory diseases.

p-Synephrine ameliorates alloxan-induced diabetes mellitus through inhibiting oxidative stress and inflammation via suppressing the NF-kappa B and MAPK pathways.

Oxidative stress and inflammation play important roles in the development of diabetes mellitus. p-Synephrine, the primary pharmacologically active protoalkaloid in Citrus species, has been popularly consumed as a dietary supplement for weight loss management. However, the effects of p-synephrine on diabetes mellitus and the action mechanisms have not been clearly elucidated. In this study, the in vitro antioxidant effects of p-synephrine were evaluated. The data showed that p-synephrine treatment exhibited significant scavenging effects against DPPH, ABTS and OH radicals and showed high reducing power. Diabetic mice were developed by alloxan injection, followed by p-synephrine administration to investigate its hypoglycemic effects in vivo. The results showed that p-synephrine intervention significantly prevented alloxan-induced alteration in body weight, organ indexes, serum uric acid content and serum creatinine content. Meanwhile, p-synephrine application significantly improved the lipid profiles, superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) contents in the serum and kidneys of diabetic mice and reduced the malondialdehyde (MDA) content in the serum of diabetic mice. Further assays suggested that p-synephrine treatment improved alloxan-induced decreases of glucose tolerance and insulin sensitivity. Also, p-synephrine supplementation altered histopathological changes in the kidneys and interscapular brown adipose tissues in diabetic mice. In addition, p-synephrine administration inhibited renal inflammation through suppressing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) gene expression levels, as well as CD45 expression levels. The anti-inflammatory effects were probably involved in the regulation of nuclear factor-κB (NF-κB) activation and mitogen-activated protein kinase (MAPK) phosphorylation. In conclusion, p-synephrine application significantly ameliorated alloxan-induced diabetes mellitus by inhibiting oxidative stress via suppressing the NF-κB and MAPK pathways.

[Effects of bone morphogenetic protein-7 therapy on E3 ubiquitin ligase expression in mouse liver with experimentally induced fibrosis].

OBJECTIVE: This study explored the dynamic expression of the E3 ubiquitin-protein ligase gene, Arkadia, in response to carbon tetrachloride (CCl4)-induced liver fibrosis in a mouse model and investigated the differential expression that occurs following treatment with the anti-fibrotic bone morphogenetic protein-7 (BMP-7). METHODS: Thirty healthy male imprinting control region (ICR) mice were randomly assigned to three groups: normal (control; n = 6), CCl4-induced model group (model; n = 18), and CCl4-induced model with BMP-7 treatment group (treatment; n = 6). The model group was further divided into three subgroups (n = 6 each) for analysis at 4, 8 and 12 weeks after fibrosis induction. Liver fibrosis was induced by hypodermic injections of 60% CCl4 /peanut oil (5 mL/kg) to the hind legs of mice two-times per week in alternating legs for a period of 12 weeks. At week 9, the treatment group of CCl4-induced mice were given an intraperitoneal injection of BMP-7 (300 pg/g) simultaneously with that day's hypodermic injection of 60% CCl4 /peanut oil, and then every other day for a period of four weeks. The pathological changes in liver tissues were observed after staining with hematoxylin-eosin (HE) and Masson's trichrome. Messenger RNA (mRNA) and protein expression of Arkadia in liver were evaluated using reverse transcription-polymerase chain reaction and immunohistochemistry and Western blotting, respectively. RESULTS: Mouse models of liver fibrosis were successfully established by CCl4 exposure. Arkadia, Smad7 and TGF-beta1 mRNA levels were up-regulated in the model group in a time-dependent manner (vs. control group), and BMP-7 treatment led to significant down-regulation of the CCl4-induced expression of the three genes (vs. control group: F = 812.80, 451.46, and 998.96, respectively; P less than 0.01). At week 12, the mRNA levels of Arkadia, Smad7, and TGF-b1 were significantly lower in the BMP-7 treatment group than in the model group (t = 12.108, 18.737, and 16.364, respectively; P less than 0.01). Arkadia, Smad7, and TGF-b1 protein staining was weak in the portal area of control liver tissue. In contrast, the model group showed significantly stronger staining for all three proteins in the portal area and in the cytoplasm of liver cells. The staining of Arkadia, Smad7, and TGF-b1 proteins was significantly lower in the treatment group (vs. control group: F = 8.399, 609.690, and 900.561, respectively; P < 0.01). At week 12, the protein levels of Arkadia, Smad7, and TGF-b1 were significantly lower in the treatment group than in the model group (t = 23.438, 11.667, and 42.889, respectively; P < 0.01). CONCLUSION: Arkadia expression gradually increased along with the development of liver fibrosis but was suppressed by treatment with the anti-fibrotic factor, BMP-7.

Role of polyphenols from Polygonum multiflorum Caulis in obesity-related disorders.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygoni Multiflori Caulis (PMC) has been widely consumed as folk medicine in China for anti-obesity, sleep-enhancing and many other pharmacological effects. However, the material basis and underlying mechanism of PMC on obesity-related disorders were still not clear. AIM OF THE STUDY: To screen active constituents from PMC and explore their multitarget mechanisms in the treatment of obesity and its associated disorders. MATERIALS AND METHODS: Several major constituents were extracted from PMC and LC-MS assay were used to identify the compounds. The lipase inhibitory activity and lipid accumulation in 3T3-L1 preadipocytes were determined. Furthermore, Caenorhabditis elegans (C. elegans) and high-fat diet (HFD)-induced mice were established to explore the potential pharmacological functions and related mechanisms using kits, RT-qPCR and biochemical analysis. RESULTS: Regarding the lipase inhibitory activity, the inhibition rate of EA and n-Bu extracts at 4 mg/mL reached over 80%. Effects on 3T3-L1 preadipocytes proliferation and differentiation were also obvious, indicating that EA and n-Bu extracts might exert potential anti-obesity functions. LC-MS assay further showed that polyphenols including emodin and physcion comprised majority of EA and n-Bu extracts. EA and n-Bu extracts treatment could significantly modulate the antioxidant response and lipid accumulation in C. elegans, as evidenced by increased SOD and CAT contents, reduced MDA levels, higher TG contents and changes of related mRNA expression levels. In HFD-induced mice, the inhibition ratio of body weight as well as the histological and biochemical indexes of liver, plasma and epididymal adipose tissues were also reversed by EA and n-Bu extracts treatment. Moreover, EA and n-Bu extracts administration increased the microbial diversity, reshaped the microbiota structure and enhanced the relative abundance of Bifidobacterium. CONCLUSIONS: This study demonstrated the multicomponent and multitarget characteristics of PMC in preventing obesity related disorders. The results provided novel insights for the development and utilization of PMC.

Optimization of the extract from flower of Citrus aurantium L. var. amara Engl. and its inhibition of lipid accumulation.

Flower of Citrus aurantium L. var. amara Engl. (CAVA) has been confirmed to have promising anti-obesity effects. However, the regulation of alkaloid extracts from flower of CAVA (Al) on lipid metabolism remain unknown. In this study, Al was optimized by ultrasound-assisted extraction using response surface methodology. The optimal conditions were ultrasonic time 72 min, ethanol concentration 78% and liquid/solid ratio 30 ml/g with the maximum alkaloid yield 5.66%. LC-MS assay indicated that the alkaloid compounds were enriched in Al after optimization. Nine alkaloid compounds were identified in Al by LC-MS assay and stachydrine, caffeine and cathine appeared as the major alkaloid compounds. Bioactivity assay showed that Al treatment significantly increased superoxide dismutase (SOD) activity, and reduced malonaldehyde (MDA) and reactive oxygen species (ROS) levels. Al administration also reversed oleic acid-induced hepatic steatosis in Hep G2 cells by inhibiting the expression of lipogenesis-signaling genes including fatty acid synthase (FAS), peroxisome proliferator-activated receptor subtype γ (PPARγ), uncoupling protein 2 (UCP2), and retinol binding protein (RBP4). However, OA-induced reduction of lipolysis-related gene carnitine palmitoyl transferase 1A (CPT1A) in Hep G2 cells was not improved by Al supplementation. Moreover, the increased SOD activity and decreased MDA and ROS contents were also observed in Caenorhabditis elegans by Al addition. Al intervention exhibited the ability to inhibit lipid accumulation in C. elegans by suppressing expression of lipid metabolism-related genes. These results suggested that the alkaloid extracts from the flower of CAVA showed great potential to regulate lipid metabolism. PRACTICAL APPLICATIONS: The extraction of alkaloid extracts from the flower of CAVA was optimized with a maximum yield of 5.66%. The regulatory effects and mechanisms of Al on lipid metabolism of Hep G2 cells and Caenorhabditis elegans were also investigated. More clinical studies are required to evaluate the potential of using alkaloids from the flower of CAVA as therapeutic agents against lipid metabolic disorders.

Explore the Anti-Acne Mechanism of Licorice Flavonoids Based on Metabonomics and Microbiome.

Acne vulgaris is one of the most common inflammatory dermatoses in dermatological practice and can affect any gender or ethnic group. Although in previous studies, we had found that licorice flavonoids (LCF) play an anti-acne role by inhibiting PI3K-Akt signaling pathways and mitochondrial activity, the mechanism of LCF regulating skin metabolism, serum metabolism and skin microbes is still unclear. Here, we performed a full spectrum analysis of metabolites in the skin and serum using UHPLC-Triple TOF-MS. The results showed that LCF could treat acne by regulating the metabolic balance of amino acids, lipids and fatty acids in serum and skin. Similarly, we performed Illumina Hiseq sequencing of DNA from the skin microbes using 16S ribosomal DNA identification techniques. The results showed that LCF could treat acne by regulating the skin microbes to interfere with acne and make the microecology close to the normal skin state of rats. In summary, this study confirmed the anti-acne mechanism of LCF, namely by regulating metabolic balance and microbial balance. Therefore, this discovery will provide theoretical guidance for the preparation development and clinical application of the drug.

Structural characterization of novel arabinoxylan and galactoarabinan from citron with potential antitumor and immunostimulatory activities.

This study aimed to extract polysaccharides from citron and analyze their structures and potential bioactivities. Two novel polysaccharides CM-1 and CM-2 were purified from citron by DEAE-Sepharose Fast Flow and Sephadex G-100 column chromatography. Monosaccharide composition, linkage and NMR data were used to infer their sugar chains composition. The anti-breast cancer cells and immunoregulatory activities of CM-1 and CM-2 were investigated. Results indicated that CM-1 (Mw = 21,520 Da), composed of arabinose, xylose, mannose and glucose in a molar ratio of 10.78:11.53:1.00:1.70, was arabinoxylan (AX) with (1 â†’ 4)-linked ß-d-Xylp skeleton monosubstituted with α-l-Araf units at O-3 position. While CM-2 (Mw = 22,303 Da), composed of arabinose, mannose, glucose and galactose in a molar ratio of 25.46:1.45:1.00:6.57, was galactoarabinan (GA) with (1 â†’ 5)-linked α-l-Araf backbone substituted by ß-d-Galp units at O-2 and/or O-3 positions. Both polysaccharides exhibited potential inhibiting cancer and immunostimulatory activities in vitro, especially CM-1. These results provide a basis for further research on citron polysaccharides.

Targets and underlying mechanisms related to the sedative and hypnotic activities of saponins from Rhodiola rosea L. (crassulaceae).

Rhodiola rosea L. (Crassulaceae) are popularly used as a natural supplement for the treatment of insomnia and anxiety. Here, saponin extracts from R. rosea were investigated for their roles on relieving sleeplessness. The levels of neurotransmitters, hormones, and inflammation cytokines in plasma, and the expression of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), prostaglandin D2 (PGD2), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in the hypothalamus and hippocampus were detected using ELISA, RT-PCR, and western blotting. First, the butanol fraction extracted from R. rosea was collected as the total saponins (HJT-I), then a saponin-rich fraction (HJT-II) was obtained after the further purification of HJT-I. The saponin contents of HJT-I and HJT-II were 28.92% and 65.69%, respectively. Second, behavioral tests were performed and showed that both HJT-I and HJT-II could effectively reduce the duration of immobility in the tail suspension test, and shorten sleep latency and prolong the sleep duration time in the sodium barbital-induced sleeping test, with HJT-II better than HJT-I. Third, ELLISA results showed that the concentrations of GABA, 5-HT, norepinephrine (NA), PGD2, and IL-1ß in plasma were significantly increased after HJT-I and HJT-II administration, while IL-6 was decreased. HJT-I and HJT-II also exhibited differential modulation of the receptors of 5-HT, GABA, PGD2, and IL-1ß expression. In hypothalamus, HJT-II was more powerful than HJT-I in regulation of the GABAARα2, GABAARα3, and glutamic acid decarboxylase (GAD) 65/67 expression, as well as 5-HT2A and IL-1ß. As for DPR and PGD2, HJT-II was more effective in the hippocampus. The efficacy of HJT-I was better than HJT-II at stimulating GABAARα2, GAD 65/67, 5-HT1A, and IL-1ß expression in the hippocampus. In conclusion, the potential sedative and hypnotic effects of HJT-I and HJT-II may possibly be related to the serotonergic, GABAAergic, and immune systems, while the underlying mechanism of HJT-I and HJT-II differed from each other.

Flavonoids from Rosa davurica Pall. fruits prevent high-fat diet-induced obesity and liver injury via modulation of the gut microbiota in mice.

Rosa davurica Pall. (RDP) fruits are popularly consumed as beverages and healthy food in China because of their various beneficial activities. In particular, flavonoids are one of the major active ingredients of RDP fruits with predominant pharmacological effects. However, the anti-obesity activities of flavonoids from RDP fruits and their regulation effect on the gut microbiota have not been determined. In the present study, the flavonoid-rich extracts (RDPF) were isolated from RDP fruits and their anti-obesity effects were investigated using a high-fat diet (HFD)-induced obese mouse model. The results showed that RDPF intervention significantly inhibited the body weight, liver weight, kidney weight and epididymal adipose tissue weight of HFD-fed mice without affecting the calorie intake. Plasma lipid levels were also significantly lowered by RDPF treatment. Histological examination showed that RDPF supplementation partially recovered HFD-induced hepatic steatosis in the liver. RDPF also prevented oxidative injury of the liver, as evidenced by the altered superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels. The expression levels of CCAAT/enhancer binding protein α (C/EBPα), sterol regulatory element binding protein-1C (SREBP-1C), fatty acid synthase (FAS), acyl-coenzyme A oxidase 1 (ACOX1), peroxisome proliferator-activated receptor (PPARα) and CAT mRNA in the livers of mice were also regulated by RDPF administration. 16S rRNA gene sequence data further indicated that RDPF addition increased the microbial diversity and reshaped the community composition. Intriguingly, RDPF intervention did not exhibit inhibitory tendency toward the ratio of Firmicutes to Bacteroidetes, but markedly decreased the relative abundance of Erysipelotrichaceae. This study provided novel insights into the application of RDPF in the food industry.