Effects of Fermented Extracts of Wuniuzao Dark Loose Tea on Hepatic Sterol Regulatory Element-Binding Protein Pathway and Gut Microbiota Disorder in Obese Mice.

BACKGROUND: Artificially fermented dark loose tea is a type of novel dark tea prepared via fermentation by Eurotium cristatum. The effects of artificially fermented dark loose tea on lipid metabolism are still unclear. OBJECTIVES: This study aimed to explore if artificially fermented dark loose tea has the same effects as naturally fermented dark loose tea in regulating hepatic lipid metabolism. METHODS: Thirty-six 8-wk-old male C57BL/6 mice were randomly divided into 6 treatment groups, including normal control (NC), high-fat diet (HFD), positive control (PC), Wuniuzao dark raw tea (WDT), Wuniuzao naturally fermented dark loose tea (NFLT), and Wuniuzao artificially fermented dark loose tea (AFLT) groups. The HFD, PC, WDT, NFLT, and AFLT groups were fed a HFD. The PC group was supplemented with atorvastatin (10 mg/kg). The WDT group was supplemented with WDT (300 mg/kg), the NFLT group with NFLT (300 mg/kg), and the AFLT group with AFLT (300 mg/kg). RESULTS: The study compared the effect of WDT, NFLT, and AFLT on liver steatosis and gut microbiota disorder in obese mice. All 3 tea extracts reduced body weight, glucose tolerance, and serum lipid concentrations. Via sterol-regulatory element binding protein (SREBP)-mediated lipid metabolism, all 3 tea extracts alleviated hepatic steatosis in mice with obesity. Furthermore, NFLT and AFLT intervened in the abundance of Firmicutes, Bacteroidetes, Clostridia, Muribaculaceae, and Lachnospiraceae. CONCLUSION: In mice with obesity induced by a HFD, WDT, NFLT, and AFLT may improve hepatic steatosis through an SREBP-mediated lipid metabolism. Moreover, NFLT and AFLT improved the composition of gut microbiota.

Anxiolytic interventions of extracts and pure compounds from Adenanthera pavonina and Peltophorum pterocarpum leaves to treat acute anxiety and depression symptoms in mice.

Anxiolytic effect of ethanol, hexane extracts and pure compounds ß- sito sterol glucoside and bergenin isolated from Adenanthera pavonina AP (Fabaceae) and Peltophorum pterocarpum PP (Fabaceae) leaves were monitored in this study. Mice were treated with dose of 125mg/kg body weight of ethanol and hexane leaves extracts of both tested plants while, 5mg/kg body weight of ß-sito sterol glucoside and 25mg/kg body weight of bergenin. The effect was monitored by hole board test, forced swimming test, open field apparatus and stationary rod test. Results from neuropharmacological effects revealed that ethanol extract of AP leaves and hexane extract of PP leaves had significant anxiolytic (forced swimming test) exploratory (head dip and open field test) and neuro activator activity (stationary rod test) at tested dose. The greatest anti-depressant and anxiolytic effect was found in ethanol extract of AP leaves when compared to all treated drugs. A part from memory enhancing effects, diazepam treated mice also exhibited anxiolytic and antidepressant effects and found comparable with ethanol extract of AP. These findings may clarify the impact of ethanol, hexane extracts and pure substances ß-sitosterol glucoside and bergenin at tested concentrations, as well as their potential to treat the Parkinson's and related disorders as an alternative therapy.

Honokiol Inhibits the Inflammatory Response and Lipid Metabolism Disorder by Inhibiting p38α in Alcoholic Liver Disease.

Alcoholic liver disease is one of the leading causes of liver-related morbidity and mortality worldwide, but effective treatments are still lacking. Honokiol, a lignin-type natural compound isolated from the leaves and bark of Magnolia plants, has been widely studied for its beneficial effects on several chronic diseases. Accumulating studies have revealed that honokiol displays a potential therapeutic effect on alcoholic liver disease. In this study, the protective activity of honokiol on alcoholic liver disease was confirmed due to its significant inhibitory activity on the expression levels of inflammatory cytokines (such as tumor necrosis factor-alpha, interleukin-6, and interleukin-1ß) in EtOH-fed mice and in EtOH-induced AML-12 cells. Meanwhile, the expression of the lipid metabolic parameter sterol regulatory element-binding protein-1c was also reduced. However, peroxisome proliferator-activated receptor α was increased in animal and cell experiments, which indicates that the activity of honokiol was related to its regulated activity on lipid metabolism. The result showed that honokiol significantly inhibited the expression level of p38α in vivo and in vitro. Blocking p38α inhibited the expression levels of tumor necrosis factor-alpha, interleukin-6, interleukin-1ß, and sterol regulatory element-binding protein-1c but promoted the expression level of peroxisome proliferator-activated receptor α compared with the honokiol-treated group. Moreover, the forced expression level of p38α further produced the opposite effect on inflammatory cytokines and lipid metabolism indicators. Furthermore, p38α has been related to the activation of the nuclear factor kappa B signaling pathway. In our study, honokiol significantly inhibited the activation of the nuclear factor kappa B signaling pathway mediated by p38α. In conclusion, the results suggest that honokiol might be an effective regulator of p38α by downregulating the nuclear factor kappa B signaling pathway, thereby reducing the inflammatory response and lipid metabolism disorder in alcoholic liver disease.

Identification of a Hydroxygallic Acid Derivative, Zingibroside R1 and a Sterol Lipid as Potential Active Ingredients of Cuscuta chinensis Extract That Has Neuroprotective and Antioxidant Effects in Aged Caenorhabditis elegans.

We examined the effects of the extracts from two traditional Chinese medicine plants, Cuscuta chinensis and Eucommia ulmoides, on the healthspan of the model organism Caenorhabditis elegans. C. chinensis increased the short-term memory and the mechanosensory response of aged C. elegans. Furthermore, both extracts improved the resistance towards oxidative stress, and decreased the intracellular level of reactive oxygen species. Chemical analyses of the extracts revealed the presence of several bioactive compounds such as chlorogenic acid, cinnamic acid, and quercetin. A fraction from the C. chinensis extract enriched in zingibroside R1 improved the lifespan, the survival after heat stress, and the locomotion in a manner similar to the full C. chinensis extract. Thus, zingibroside R1 could be (partly) responsible for the observed health benefits of C. chinensis. Furthermore, a hydroxygallic acid derivative and the sterol lipid 4-alpha-formyl-stigmasta-7,24(241)-dien-3-beta-ol are abundantly present in the C. chinensis extract and its most bioactive fraction, but hardly in E. ulmoides, making them good candidates to explain the overall healthspan benefits of C. chinensis compared to the specific positive effects on stress resistance by E. ulmoides. Our findings highlight the overall anti-aging effects of C. chinensis in C. elegans and provide first hints about the components responsible for these effects.

New insights into the antiviral activity of nordihydroguaiaretic acid: Inhibition of dengue virus serotype 1 replication.

BACKGROUND: Dengue virus (DENV) is considered one of the most important pathogens in the world causing 390 million infections each year. Currently, the development of vaccines against DENV presents some shortcomings and there is no antiviral therapy available for its infection. An important challenge is that both treatments and vaccines must be effective against all four DENV serotypes. Nordihydroguaiaretic acid (NDGA), isolated from Larrea divaricata Cav. (Zygophyllaceae) has shown a significant inhibitory effect on a broad spectrum of viruses, including DENV serotypes 2 and 4. PURPOSE: We evaluated the in vitro virucidal and antiviral activity of NDGA on DENV serotype 1 (DENV1), including the study of its mechanism of action, to provide more evidence on its antiviral activity. METHODS: The viability of viral particles was quantified by the plaque-forming unit reduction method. NDGA effects on DENV1 genome and viral proteins were evaluated by qPCR and immunofluorescence, respectively. Lysosomotropic activity was assayed using acridine orange and neutral red dyes. RESULTS: NDGA showed in vitro virucidal and antiviral activity against DENV1. The antiviral effect would be effective within the first 2 h after viral internalization, when the uncoating process takes place. In addition, we determined by qPCR that NDGA decreases the amount of intracellular RNA of DENV1 and, by immunofluorescence, the number of cells infected. These results indicate that the antiviral effect of NDGA would have an intracellular mechanism of action, which is consistent with its ability to be incorporated into host cells. Considering the inhibitory activity of NDGA on the cellular lipid metabolism, we compared the antiviral effect of two inhibitors acting on two different pathways of this type of metabolism: 1) resveratrol that inhibits the sterol regulatory element of binding proteins, and 2) caffeic acid that inhibits the 5-lipoxygenase (5-LOX) enzyme. Only caffeic acid produced an inhibitory effect on DENV1 infection. We studied the lysosomotropic activity of NDGA on host cells and found, for the first time, that this compound inhibited the acidification of cell vesicles which would prevent DENV1 uncoating process. CONCLUSION: The present work contributes to the knowledge of NDGA activity on DENV. We describe its activity on DENV1, a serotype different to those that have been already reported. Moreover, we provide evidence on which stage/s of the viral replication cycle NDGA exerts its effects. We suggest that the mechanism of action of NDGA on DENV1 is related to its lysosomotropic effect, which inhibits the viral uncoating process.

A Nutraceutical Formulation Containing Brown Algae Reduces Hepatic Lipid Accumulation by Modulating Lipid Metabolism and Inflammation in Experimental Models of NAFLD and NASH.

Recently, some preclinical and clinical studies have demonstrated the ability of brown seaweeds in reducing the risk factors for metabolic syndrome. Here, we analyzed the beneficial effect of a nutraceutical formulation containing a phytocomplex extracted from seaweeds and chromium picolinate in animal models of liver steatosis of differing severities (rats with non-alcoholic fatty liver disease (NAFLD) and its complication, non-alcoholic steatohepatitis (NASH)). This treatment led to a significant drop in hepatic fat deposition in both models (p < 0.01 vs. untreated animals), accompanied by a reduction in plasma inflammatory cytokines, such as interleukin 6, tumor necrosis factor α, and C reactive protein, and myeloperoxidase expression in liver tissue. Furthermore, a modulation of the molecular pathways involved in lipid metabolism and storage was demonstrated, since we observed the significant reduction of the mRNA levels of fatty acid synthase, diacylglycerol acyltransferases, the sterol-binding protein SREBP-1, and the lipid transporter perilipin-2, in both treated NAFLD and NASH rats in comparison to untreated ones. In conclusion, this nutraceutical product was effective in reducing liver steatosis and showed further beneficial effects on hepatic inflammation and glycemic control, which were particularly evident in rats characterized by a more severe condition, thus representing a therapeutic option for the treatment of NAFLD and NASH patients.

Metabolomic Profiling Reveals Protective Effects and Mechanisms of Sea Buckthorn Sterol against Carbon Tetrachloride-Induced Acute Liver Injury in Rats.

The present study was designed to examine the efficacy and protection mechanisms of sea buckthorn sterol (SBS) against acute liver injury induced by carbon tetrachloride (CCl4) in rats. Five-week-old male Sprague-Dawley (SD) rats were divided into six groups and fed with saline (Group BG), 50% CCl4 (Group MG), or bifendate 200 mg/kg (Group DDB), or treated with low-dose (Group LD), medium-dose (Group MD), or high-dose (Group HD) SBS. This study, for the first time, observed the protection of SBS against CCl4-induced liver injury in rats and its underlying mechanisms. Investigation of enzyme activities showed that SBS-fed rats exhibited a significant alleviation of inflammatory lesions, as evidenced by the decrease in cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and gamma-glutamyl transpeptidase (γ-GT). In addition, compared to the MG group, the increased indices (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), total antioxidant capacity (T-AOC), and total protein (TP)) of lipid peroxidation and decreased malondialdehyde (MDA) in liver tissues of SBS-treated groups showed the anti-lipid peroxidation effects of SBS. Using the wide range of targeted technologies and a combination of means (UPLC-MS/MS detection platform, self-built database, and multivariate statistical analysis), the addition of SBS was found to restore the expression of metabolic pathways (e.g., L-malic acid, N-acetyl-aspartic acid, N-acetyl-l-alanine, etc.) in rats, which means that the metabolic damage induced by CCl4 was alleviated. Furthermore, transcriptomics was employed to analyze and compare gene expression levels of different groups. It showed that the expressions of genes (Cyp1a1, Noct, and TUBB6) related to liver injury were regulated by SBS. In conclusion, SBS exhibited protective effects against CCl4-induced liver injury in rats. The liver protection mechanism of SBS is probably related to the regulation of metabolic disorders, anti-lipid peroxidation, and inhibition of the inflammatory response.

Effects of Non-Polar Dietary and Endogenous Lipids on Gut Microbiota Alterations: The Role of Lipidomics.

Advances in sequencing technologies over the past 15 years have led to a substantially greater appreciation of the importance of the gut microbiome to the health of the host. Recent outcomes indicate that aspects of nutrition, especially lipids (exogenous or endogenous), can influence the gut microbiota composition and consequently, play an important role in the metabolic health of the host. Thus, there is an increasing interest in applying holistic analytical approaches, such as lipidomics, metabolomics, (meta)transcriptomics, (meta)genomics, and (meta)proteomics, to thoroughly study the gut microbiota and any possible interplay with nutritional or endogenous components. This review firstly summarizes the general background regarding the interactions between important non-polar dietary (i.e., sterols, fat-soluble vitamins, and carotenoids) or amphoteric endogenous (i.e., eicosanoids, endocannabinoids-eCBs, and specialized pro-resolving mediators-SPMs) lipids and gut microbiota. In the second stage, through the evaluation of a vast number of dietary clinical interventions, a comprehensive effort is made to highlight the role of the above lipid categories on gut microbiota and vice versa. In addition, the present status of lipidomics in current clinical interventions as well as their strengths and limitations are also presented. Indisputably, dietary lipids and most phytochemicals, such as sterols and carotenoids, can play an important role on the development of medical foods or nutraceuticals, as they exert prebiotic-like effects. On the other hand, endogenous lipids can be considered either prognostic indicators of symbiosis or dysbiosis or even play a role as specialized mediators through dietary interventions, which seem to be regulated by gut microbiota.

Taraxasterol mitigates Con A-induced hepatitis in mice by suppressing interleukin-2 expression and its signaling in T lymphocytes.

Discovery of anti-inflammatory drugs that can suppress T lymphocyte activation and proliferation by inhibiting TCR/CD3 and IL-2/IL-2R signaling is still needed in clinic, though rapamycin and other related reagents have made great success. Taraxasterol (TAS) is an active ingredient of dandelion, an anti-inflammatory medicinal herb with low in vivo toxicity that has long been used in China. Yet the action mechanism of TAS on lymphocytes remains elusive. The anti-inflammatory effects of TAS were evaluated in C57BL/6 mouse primary lymphocytes stimulated with concanavalin A (Con A) in vitro and in mouse model of Con A-induced acute hepatitis in vivo. Our results showed that TAS significantly suppressed Con A-induced acute hepatitis in a mouse model, reducing the hepatic necrosis areas, the release of aminotransferases, and the production of IL-2 and other inflammatory cytokines. Supporting this, in vitro study also showed that TAS reduced the production of IL-2 and the expression of IL-2 receptor subunit α (CD25) upon the stimulation of Con A, which was likely mediated by suppressing NF-κB activation. The downstream pathways of IL-2/IL-2R signaling, including the activation of PI3K/PDK1/mTOR, STAT3 and STAT5, were also suppressed by TAS. Consistently, Con A-induced T cell proliferation was also inhibited by TAS in vitro. Our data indicate that TAS can suppress both T lymphocyte activation and cell proliferation by down-regulating IL-2 expression and its signaling pathway thereby ameliorating Con A-induced acute hepatitis, highlighting TAS as a potential drug candidate for treating inflammatory diseases including autoimmune hepatitis.

Protective effect of sterols extracted from Lotus plumule on ethanol-induced injury in GES-1 cells in vitro.

In this study, sterols were isolated from Lotus plumule by Soxhlet extraction and saponification and were further characterized by GC-MS analysis. The results showed that the sterols extracted from Lotus plumule mainly contained ß-sitosterol, fucosterol, and campesterol. Models were established in vitro to investigate the protective effects of Lotus plumule sterols (LPSs) on ethanol-induced injury in human gastric epithelium (GES-1) cells. The results showed that appropriate concentrations of LPSs and ß-sitosterol could protect GES-1 cells from ethanol-induced injury by reducing ROS levels, reducing calcium ion release, increasing antioxidant enzyme activity and maintaining mitochondrial membrane potential. Western blot experiment results also showed that appropriate concentrations of LPSs and ß-sitosterol could up-regulate the expression of the anti-apoptotic protein Bcl-2 and down-regulate the pro-apoptotic proteins Bax and caspase-3 in GES-1 cells. Meanwhile, sterol pretreatment groups down-regulated the protein expression levels of p-P38 and p-JNK in ethanol-damaged GES-1 cells and up-regulated the expression level of p-ERK, suggesting that sterols protect GES-1 cells from ethanol-induced damage by regulating the MAPK signaling pathway. Taken together, Lotus plumule sterols could effectively prevent gastric cell damage in vitro and suggest the potential application of LPSs as bioactive ingredients for healthy foods.

Screening Reveals Sterol Derivatives with Pro-Differentiation, Pro-Survival, or Potent Cytotoxic Effects on Oligodendrocyte Progenitor Cells.

Inducing the formation of new oligodendrocytes from oligodendrocyte progenitor cells (OPCs) represents a potential approach to repairing the loss of myelin observed in multiple sclerosis and other diseases. Recently, we demonstrated that accumulation of specific cholesterol precursors, 8,9-unsaturated sterols, is a dominant mechanism by which dozens of small molecules enhance oligodendrocyte formation. Here, we evaluated a library of 56 sterols and steroids to evaluate whether other classes of bioactive sterol derivatives may also influence mouse oligodendrocyte precursor cell (OPC) differentiation or survival. From this library, we identified U-73343 as a potent enhancer of oligodendrocyte formation that induces 8,9-unsaturated sterol accumulation by inhibition of the cholesterol biosynthesis enzyme sterol 14-reductase. In contrast, we found that mouse OPCs are remarkably vulnerable to treatment with the glycosterol OSW-1, an oxysterol-binding protein (OSBP) modulator that induces Golgi stress and OPC death in the low picomolar range. A subsequent small-molecule suppressor screen identified mTOR signaling as a key effector pathway mediating OSW-1's cytotoxic effects in mouse OPCs. Finally, evaluation of a panel of ER and Golgi stress-inducing small molecules revealed that mouse OPCs are highly sensitive to these perturbations, more so than closely related neural progenitor cells. Together, these studies highlight the wide-ranging influence of sterols and steroids on OPC cell fate, with 8,9-unsaturated sterols positively enhancing differentiation to oligodendrocytes and OSW-1 able to induce lethal Golgi stress with remarkable potency.

Sterol sulfate alleviates atherosclerosis via mediating hepatic cholesterol metabolism in ApoE-/- mice.

Compared with terrestrial organisms, the sterols in sea cucumber exhibit a sulfate group at the C-3 position. Our previous study demonstrated that dietary sterol sulfate was superior to phytosterol in alleviating metabolic syndrome by ameliorating inflammation and mediating cholesterol metabolism in high-fat-high-fructose diet mice, which indicated its potential anti-atherosclerosis bioactivity. In the present study, administration with sea cucumber-derived sterol sulfate (SCS) significantly decreased the cholesterol level in oleic acid/palmitic acid-treated HepG2 cells, while no significant changes were observed in the triacylglycerol level. RNA-seq analysis showed that the metabolic changes were mostly attributed to the steroid biosynthesis pathway. ApoE-/- mice were used as an atherosclerosis model to further investigate the regulation of SCS on cholesterol metabolism. The results showed that SCS supplementation dramatically reduced atherosclerotic lesions by 45% and serum low-density lipoprotein cholesterol levels by 59% compared with the model group. Dietary SCS inhibited hepatic cholesterol synthesis via downregulating SREBP-2 and HMGCR. Meanwhile, SCS administration increased cholesterol uptake via enhancing the expression of Vldlr and Ldlr. Noticeably, SCS supplementation altered bile acid profiles in the liver, serum, gallbladder and feces, which might cause the activation of FXR in the liver. These findings provided new evidence about the high bioactivity of sterols with the sulfate group on atherosclerosis.

New sterols from the South China Sea sponges Halichondria sp.

A detailed chemical investigation of two specimen of South China Sea sponges Halichondria sp. (No. 19-XD-47 and No. 17-XD-87) have resulted in the isolation of three new sterols, namely, halichsterols A (1), B (2) and C (3), together with seven related known ones (4-10). Their structures were determined by extensive spectroscopic analysis and by comparison with the spectral data reported in the literature. In bioassay, compound 2 displayed significantly anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells.

Inhibition of NLRP3 Inflammasome Activation and Pyroptosis in Macrophages by Taraxasterol Is Associated With Its Regulation on mTOR Signaling.

Taraxasterol (TAS) is an active ingredient of Dandelion (Taraxacum mongolicum Hand. -Mazz.), a medicinal plant that has long been used in China for treatment of inflammatory disorders. But the underlying mechanism for its therapeutic effects on inflammatory disorders is not completely clear. Inflammasome activation is a critical step of innate immune response to infection and aseptic inflammation. Among the various types of inflammasome sensors that has been reported, NLR family pyrin domain containing 3 (NLRP3) is implicated in various inflammatory diseases and therefore has been most extensively studied. In this study, we aimed to explore whether TAS could influence NLPR3 inflammasome activation in macrophages. The results showed that TAS dose-dependently suppressed the activation of caspase-1 in lipopolysaccharide (LPS)-primed murine primary macrophages upon nigericin treatment, resulting in reduced mature interleukin-1ß (IL-1ß) release and gasdermin D (GSDMD) cleavage. TAS greatly reduced ASC speck formation upon the stimulation of nigericin or extracellular ATP. Consistent with reduced cleavage of GSDMD, nigericin-induced pyroptosis was alleviated by TAS. Interestingly, TAS time-dependently suppressed the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) and mTORC2 signaling induced by LPS priming. Like TAS, both INK-128 (inhibiting both mTORC1 and mTORC2) and rapamycin (inhibiting mTORC1 only) also inhibited NLRP3 inflammasome activation, though their effects on mTOR signaling were different. Moreover, TAS treatment alleviated mitochondrial damage by nigericin and improved mouse survival from bacterial infection, accompanied by reduced IL-1ß levels in vivo. Collectively, by inhibiting the NLRP3 inflammasome activation, TAS displayed anti-inflammatory effects likely through regulation of the mTOR signaling in macrophages, highlighting a potential action mechanism for the anti-inflammatory activity of Dandelion in treating inflammation-related disorders, which warrants further clinical investigation.

Root Extracts of Two Cultivars of Paeonia Species: Lipid Composition and Biological Effects on Different Cell Lines: Preliminary Results.

The roots of two cultivars of Paeonia, namely Paeonia officinalis "Rubra Plena" and Paeonia "Pink Hawaiian Coral", have been extracted with chloroform. The composition of the lipid fraction, analyzed by GC-MS technique, revealed the absence of paeonol and the presence of phenol, benzoic acid, fatty acid-and some sterol-derivatives. The chloroformic extracts have been tested on normal and several cancer cell lines but showed antiproliferative activity only on the ovarian carcinoma and the osteosarcoma. The biological activity of extracts was investigated mainly by confocal microscopy, flow cytometry and quantum phase imaging. The results indicated that the root extracts induced a hyperpolarization of mitochondria and an increase in reactive oxygen species levels, without inducing cell death. These effects are associated to an increased doubling time and a retarded confluence.

Network pharmacology of bioactives from Sorghum bicolor with targets related to diabetes mellitus.

BACKGROUND: Sorghum bicolor (SB) is rich in protective phytoconstituents with health benefits and regarded as a promising source of natural anti-diabetic substance. However, its comprehensive bioactive compound(s) and mechanism(s) against type-2 diabetes mellitus (T2DM) have not been exposed. Hence, we implemented network pharmacology to identify its key compounds and mechanism(s) against T2DM. METHODS: Compounds in SB were explored through GC-MS and screened by Lipinski's rule. Genes associated with the selected compounds or T2DM were extracted from public databases, and the overlapping genes between SB-compound related genes and T2DM target genes were identified using Venn diagram. Then, the networking between selected compounds and overlapping genes was constructed, visualized, and analyzed by RStudio. Finally, affinity between compounds and genes was evaluated via molecular docking. RESULTS: GC-MS analysis of SB detected a total of 20 compounds which were accepted by the Lipinski's rule. A total number of 16 compounds-related genes and T2DM-related genes (4,763) were identified, and 81 overlapping genes between them were selected. Gene set enrichment analysis exhibited that the mechanisms of SB against T2DM were associated with 12 signaling pathways, and the key mechanism might be to control blood glucose level by activating PPAR signaling pathway. Furthermore, the highest affinities were noted between four main compounds and six genes (FABP3-Propyleneglyco monoleate, FABP4-25-Oxo-27-norcholesterol, NR1H3-Campesterol, PPARA-ß-sitosterol, PPARD-ß-sitosterol, and PPARG-ß-sitosterol). CONCLUSION: Our study overall suggests that the four key compounds detected in SB might ameliorate T2DM severity by activating the PPAR signaling pathway.

Cytotoxic, Apoptosis-Inducing Activities, and Molecular Docking of a New Sterol from Bamboo Shoot Skin Phyllostachys heterocycla var. pubescens.

Phytochemical screening of nonpolar fractions from the methanol extract of the Bamboo shoot skin Phyllostachys heterocycla var. pubescens resulted in the isolation of a new sterol-glucoside-fatty acid derivative (6'-O-octadeca-8'',11''-dienoyl)-sitosterol-3-O-ß-d-glucoside (1), together with six known compounds. The chemical structures of the pure isolated compounds were deduced based on different spectral data. The isolated compounds were assessed to determine their cytotoxic activity, and the results were confirmed by determining their apoptotic activity. Compound 1 was more cytotoxic against the MCF-7 cells (IC50 = 25.8 µM) compared to Fluorouracil (5-FU) (26.98 µM), and it significantly stimulated apoptotic breast cancer cell death with 32.6-fold (16.63% compared to 0.51 for the control) at pre-G1 and G2/M-phase cell cycle arrest and blocked the progression of MCF-7 cells. Additionally, RT-PCR results further confirmed the apoptotic activity of compound 1 by the upregulation of proapoptotic genes (P53; Bax; and caspases 3, 8, and 9) and downregulation of the antiapoptotic genes (BCL2). Finally, the identified compounds, especially 1, were found to have high binding affinity towards both tyrosine-specific protein kinase (TPK) and vascular endothelial growth factor receptor (VEGFR-2) through the molecular docking studies that highlight its mode of action.

Cytotoxic polyhydroxy sterols from the Egyptian Red Sea soft coral Sarcophyton acutum.

The methanolic extract and its sub-extracts (viz, n-hexane, DCM, EtOAc and MeOH) of the soft coral Sarcophyton acutum were evaluated as anti-Leishmania major and as anticancer (against the HepG2, MCF-7, and A549 cell lines) using the MTT assay. Six polyhydroxy sterols (1-6) were isolated from the most active cytotoxic and anti-leishmanial EtOAc-soluble fraction. Their structures were established as two new polyhydroxy sterols, acutumosterols A (1) and B (2), and four known structural analogues (3-6) by intensive spectroscopic analyses, and by comparison with data of related compounds. Compound 4 exerted noticeable cytotoxicity against HepG2 cell line (IC50 17.2 ± 1.5 µg/mL), while the other pure isolates showed weak to moderate cytotoxicity (24.8 ± 2.8-57.2 ± 5.2). The results were discussed in relation to the structural features of these closely related sterols.

Cichorins D-F: Three New Compounds from Cichorium intybus and Their Biological Effects.

Cichorium intybus L., (chicory) is employed in various traditional medicines to treat a wide range of diseases and disorders. In the current investigation, two new naphthalane derivatives viz., cichorins D (1) and E (2), along with one new anthraquinone cichorin F (3), were isolated from Cichorium intybus. In addition, three previously reported compounds viz., ß-sitosterol (4), ß-sitosterol ß-glucopyranoside (5), and stigmasterol (6) were also isolated from Cichorium intybus. Their structures were established via extensive spectroscopic data, including 1D (1H and 13C) and 2D NMR (COSY, HSQC and HMBC), and ESIMS. Cichorin E (2) has a weak cytotoxic effect on breast cancer cells (MDA-MB-468: IC50: 85.9 µM) and Ewing's sarcoma cells (SK-N-MC: IC50: 71.1 µM); cichorin F (3) also illustrated weak cytotoxic effects on breast cancer cells (MDA-MB-468: IC50: 41.0 µM and MDA-MB-231: IC50: 45.6 µM), and SK-N-MC cells (IC50: 71.9 µM). Moreover compounds 1-3 did not show any promising anthelmintic effects.

Reversal of heavy metal-induced antibiotic resistance by dandelion root extracts and taraxasterol.

Introduction. Metal exposure is an important factor for inducing antibiotic resistance in bacteria. Dandelion extracts have been used for centuries in traditional Chinese and Native American medicine.Aim. We assessed the effects of dandelion water extracts and taraxasterol on heavy metal-induced antibiotic resistance in Escherichia coli as well as the underlying mechanisms.Methodology. Dandelion extracts were obtained through 4 h of boiling in distilled water. Bacterial growth was monitored with a spectrophotometer. Biochemical assays were performed to assess the activities and gene transcriptions of ß-lactamase and acetyltransferase. Oxidative stress was determined using an oxidation-sensitive probe, H2DCFDA.Results. The present study demonstrated that higher concentrations of nickel (>5 µg ml-1), cadmium (>0.1 µg ml-1), arsenic (>0.1 µg ml-1) and copper (>5 µg ml-1) significantly inhibited the growth of E. coli. Lower concentrations of nickel (0.5 µg ml-1), cadmium (0.05 µg ml-1) and arsenic (0.05 µg ml-1) had no effect on bacterial growth, but helped the bacteria become resistant to two antibiotics, kanamycin and ampicillin. The addition of dandelion root extracts and taraxasterol significantly reversed the antibiotic resistance induced by these heavy metals. The supplements of antibiotics and cadmium generated synergistic effects on the activities of ß-lactamase and acetyltransferase (two antibiotic resistance-related proteins), which were significantly blocked by either dandelion root extract or taraxasterol. In contrast, oxidative stress was not involved in the preventative roles of dandelion root extracts and taraxasterol in heavy metal-induced antibiotic resistance.Conclusion. This study suggests that heavy metals induce bacterial antibiotic resistance and dandelion root extracts and taraxasterol could be used to help reverse bacterial resistance to antibiotics.