The effect of Tai Chi/Qigong on depression and anxiety symptoms in adults with Cancer: A systematic review and meta-regression.

OBJECTIVE: We expand on prior systematic reviews of Tai chi/Qigong (TCQ) practice on depression or anxiety symptoms in adults with cancer to estimate the mean effect of TCQ on depression and anxiety in randomized controlled trials. Additionally, we perform moderator analysis to examine whether effects vary based on patient features, TCQ stimuli properties, or characteristics of research design. METHODS: Guided by PRISMA guidelines, we located articles published before August 31, 2023 using a combination of electronic database search and a complementary manual search through reference lists of articles and published reviews. Two separate multilevel meta-analyses with random-effects model were employed to estimate the overall effect of TCQ on depression and anxiety respectively. Further, multilevel meta-regression analysis was utilized to examine moderating effects based on moderators derived from patient features, TCQ stimuli properties, or characteristics associated with research design. Meta-analyses were performed in R4.0.0 and certainty of evidence with GRADEpro software. RESULTS: The TCQ intervention yielded a standardized mean effect size of 0.29 (95% CI, 0.18 to 0.40) for anxiety, indicating homogeneity among the included studies. Conversely, for depression, the standardized mean effect size was 0.35 (95% CI, 0.14 to 0.55), signifying heterogeneity: reductions were larger when the trial primary outcome, predominantly function-related outcomes, changed significantly between the TCQ and control group. CONCLUSIONS: TCQ practice exhibits small-to-moderate efficacy in alleviating depression and anxiety symptoms among cancer patients and survivors. Moreover, patients with depressive symptoms for whom TCQ intervention coupled with improvements in function-related outcomes manifested greater antidepressant effect.

A novel deep eutectic solvent modified magnetic covalent organic framework for the selective separation and determination of trace copper ion in medicinal plants and environmental samples.

BACKGROUND: Pretreatment techniques should be introduced before metal ion determination because there is very low content of heavy metals in Chinese medicinal plants and environmental samples. Magnetic dispersive micro solid phase extraction (MDMSPE) has been widely used for the separation and adsorption of heavy metal pollutants in medicinal plants and environmental samples. However, the majority of MDMSPE adsorbents have certain drawbacks, including low selectivity, poor anti-interference ability, and small adsorption capacity. Therefore, modifying currently available adsorption materials has gained attention in research. RESULTS: In this study, a novel adsorbent MCOF-DES based on a magnetic covalent organic framework (MCOF) modified by a new deep eutectic solvent (DES) was synthesized for the first time and used as an adsorbent of MDMSPE. The MDMSPE was combined with inductively coupled plasma optical emission spectrometry (ICP-OES) for selective separation, enrichment, and accurate determination of trace copper ion (Cu2+) in medicinal plants and environmental samples. Various characterization results show the successful preparation of new MCOF-DES. Under the optimal conditions, the enrichment factor (EF) of Cu2+ was 30, the limit of detection (LOD) was 0.16 µg L-1, and the limit of quantitation (LOQ) was 0.54 µg L-1. The results for the determination of Cu2+ were highly consistent with those of inductively coupled plasma mass spectrometry (ICP-MS), which verified the accuracy and reliability of the method. SIGNIFICANCE: The established method based on a new adsorption material MCOF-DES has achieved the selective separation and determination of trace Cu2+ in medicinal and edible homologous medicinal materials (Phyllanthus emblica Linn.) and environmental samples (soil and water), which provides a promising, selective, and sensitive approach for the determination of trace Cu2+ in other real samples.

The comparative effects of Tai chi versus non-mindful exercise on measures of anxiety, depression and general mental health: A systematic review and meta-analysis.

BACKGROUND: Tai chi has been commonly used as an allied health strategy that can support the improvement of mental health for individuals, yet the comparative effects of Tai chi versus non-mindful exercise on measures of anxiety, depression and general mental health are unknown. This study aims to quantitatively estimate the comparative effects between Tai chi and non-mindful exercise on measures of anxiety, depression, and general mental health and examine whether selected moderators of theoretical or practical importance moderate the effects. METHODS: Consistent with PRISMA guidelines for conduct and reporting, we located articles published before 31 Dec 2021 using Google Scholar, Pubmed, Web of Science, EBSCO (PsycArticles, PsycExtra, PsycInfo, Academic Search Premier, ERIC, MEDLINE). To be included in the analysis, studies were required to have (1) a design that randomly assigned participants to Tai chi and non-mindful exercise comparison condition or group. (2) anxiety, depression, or general mental health outcome measured at baseline and during or after Tai chi and exercise intervention. Study quality was judged using the tool for assessing study quality and reporting in exercise (TESTEX) for randomized controlled trials (RCTs). Three separate multilevel meta-analyses with random effects were performed to estimate the comparative effects of Tai chi versus non-mindful exercise on psychometric measures of anxiety, depression, and general mental health respectively. In addition, possible moderators were assessed accordingly for each meta-analysis. RESULTS: Twenty-three studies that included measures of anxiety (10), depression (14), and general mental health (11) involved 4370 participants (anxiety, 950; depression, 1959; general mental health,1461) and yielded 30 effects on anxiety, 48 on depression, and 27 on general mental health outcomes. Tai Chi training consisted of 1-5 sessions per week, 20-83 min per session, and 6-48 weeks. After adjusting for nesting effects, the results showed significant small-to-moderate effects of Tai chi versus non-mindful exercise on the measure of anxiety (d = 0.28, 95 % CI, 0.08 to 0.48), depression (d = 0.20, 95 % CI, 0.04 to 0.36), and general mental health (d = 0.40, 95 % CI, 0.08 to 0.73). Further moderator analyses showed that baseline general mental health T-score and study quality influenced the effects of Tai chi versus non-mindful exercise on measure of general mental health. CONCLUSION: Compared to non-mindful exercise, the small body of studies reviewed here tentatively supports that Tai chi is more effective in reducing anxiety and depression and improving general mental health than non-mindful exercise. Higher-quality trials are needed to standardize Tai chi and non-mindful exercise exposure, quantify mindfulness elements in Tai chi practice, and control expectations on conditions to better determine the psychological effects of both exercise properties.

Determination of 44 major components and chemical profiling of saccharide in Chinese medicinal formula Lanqin Oral Liquid.

INTRODUCTION: Lanqin Oral Liquid (LQL) is a traditional Chinese medicine preparation (TCMP) containing five herbal medicines and has been commonly used for the treatment of pharyngitis and hand-foot-and-mouth disease in clinic. The material basis of LQL has been reported in our previous study, but the contents of the major components and the features of saccharide in LQL are still unclear. OBJECTIVES: This study aimed to establish accurate and rapid methods for the quantification of the major components and profiling of saccharide in LQL. The quantitative results combined with similarity evaluation were applied to improve the quality control of LQL. METHODOLOGY: An ultra-high performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UPLC-QQQ-MS) method was utilised to determine 44 major components. Cosine similarity was used to evaluate the similarities among 20 batches of LQL based on the quantitative results of 44 major components. The physicochemical properties, structure, composition, and contents of saccharide in LQL were detected by a combination of chemical and instrumental analysis. RESULTS: A total of 44 compounds, including flavonoids, iridoid glycosides, alkaloids, and nucleosides, were accurately determined. The 20 batches of LQL were remarkably similar (> 0.95). In addition, d-glucose, galactose, d-glucuronic acid, arabinose, and d-mannose were detected in saccharide of LQL. The contents of saccharide in LQL were 13.52-21.09 mg/ml. CONCLUSIONS: The established methods can be applied for the comprehensive quality control of LQL, including characterisation of saccharide and quantification of representative components. Our study will provide a robust chemical foundation for disclosing the quality markers of its therapeutic effect.

Characterization and comparison of polysaccharides from Achyranthes bidentata, Cyathula officinalis and Achyranthes aspera by saccharides mapping.

Although the roots of Achyranthes bidentata (AB), Cyathula officinalis (CO) and Achyranthes aspera (AA) are different drugs, they are always confused in clinical practice due to their similar chemical components and functions. As polysaccharides are abundant in these drugs, a systematic comparison of polysaccharides from AB, CO and AA is not only necessary to understand their similar but not identical functions, but also helpful for the quality control of them. In this study, polysaccharides from 22 batches of AB, CO and AA were compared with monosaccharide composition, molecular weight distribution and saccharide mapping. Polysaccharides of AB, CO and AA had similar monosaccharide compositions but their relative contents of fructose, glucuronic acid, galacturonic acid and glucose were significant different, and could be used as key markers to distinguish them. Results from molecular weight distribution and saccharide mapping showed polysaccharides from AB, CO and AA were mainly composed of fructans with ß-2,1 and ß-2, 6-D-fructosidic linkages, but their degree of polymerization were different. Meanwhile, pectins were also contained in these three drugs. AB is partial to immunomodulation while CO is partial to removing blood stasis. Fructans and pectins are the similar bioactive substance basis of AB, CO and AA whereas their structural difference might be contributed to the efficacy differentia of these three drugs. This study provides a better understanding on the profiles of polysaccharides from AB, CO and AA, further guiding their clinical usage and facilitating their quality control.

Simiao Wan modulates the gut microbiota and bile acid metabolism during improving type 2 diabetes mellitus in mice.

BACKGROUND: Gut microbiota coupled with their metabolites (bile acids, BAs) get involved in diabetic pathogenesis. Simiao Wan is a famous traditional Chinese formula consisting on Phellodendron chinense C.K.Schneid. (Rutaceae), Atractylodes lancea (Thunb.) DC. (Asteraceae), Achyranthes bidentata Blume (Amaranthaceae) and Coix lacryma-jobi var. ma-yuen (Rom.Caill.) Stapf (Poaceae), and used to treat gouty arthritis and hyperuricemia for thousands of years. However, the mechanisms underlying its beneficial efficacy on diabetes still needs to be explored. PURPOSE: Our study was performed to reveal the effects of the 75% ethanol extraction of Simiao Wan (SMW) on diabetes, gut microbiota and bile acids (BAs) in diabetic mice. METHODS: The effects of SMW on diabetes were evaluated in mice treated by high-fat diet (HFD)/streptozotocin (STZ). The 16S rDNA sequencing and BAs metabolomics were performed to assess the changes of BAs profiles and gut microbiota induced by SMW. Western blot and real-time quantitative PCR were conducted to evaluate the possible mechanism of SMW. RESULTS: SMW significantly improved insulin resistance and hepatic lipid accumulation in HFD/STZ mice. It remarkably enriched in the bacteria Allobaculum, Clostridium, Akkermansia, Lactobacilus and Bilophila whereas decreased Coprococcus and Halomonas in diabetic mice. Furthermore, the profiles of BAs were also modulated by SMW, indicated by the reduction of conjugated BAs and 12α-OH/non-12α-OH BAs ratio in liver as well as the increase of primary BAs in feces. SMW also activated farnesoid X receptor and inhibited sterol regulatory element-binding protein-1 expression, contributing to its beneficial actions on lipid accumulation in liver. CONCLUSION: Our results showed that SMW exerted its beneficial effects on insulin resistance and hepatic lipid accumulation indirectly through regulating profiles of gut microbe and BAs.

Effective fraction from Simiao Wan prevents hepatic insulin resistant by inhibition of lipolysis via AMPK activation.

Simiao Wan (SMW) is a traditional Chinese formula, including Atractylodis Rhizoma, Achyranthis Bidentatae Radix, Phellodendri Chinensis Cortex and Coicis Semen at the ratio of 1:1:2:2. It can be used to the treatment of diabetes. However, its bioactive compounds and underlying mechanism are unclear. This study aimed to screen the antilipolytic fraction from SMW and investigate its therapeutic mechanisms on hepatic insulin resistance. Different fractions of SMW were prepared by membrane separation combined with macroporous resin and their antilipolytic activities were screened in fasted mice. The effects of 60% ethanol elution (ESMW) on lipolysis were investigated in 3T3-L1 adipocytes stimulated by palmitic acid (PA) and high fat diet (HFD)-fed mice. In our study, ESMW is the bioactive fraction responsible for the antilipolytic activity of SMW and 13 compounds were characterized from ESMW by UHPLC-QTOF-MS/MS. ESMW suppressed protein kinase A (PKA)-hormone-sensitive lipase (HSL) related lipolysis and increased AMP-activated protein kinase (AMPK) phosphorylation in PA challenged 3T3-L1 adipocytes. AMPKα knockdown abolished the inhibitory effects of ESMW on IL-6 and HSL pSer-660, revealing that the antilipolytic and anti-inflammatory activities of ESMW are AMPK dependent. Furthermore, ESMW ameliorated insulin resistance and suppressed lipolysis in HFD-fed mice. It inhibited diacylglycerol accumulation in the liver and inhibited hepatic gluconeogenesis. Conditional medium collected from ESMW-treated 3T3-L1 cells ameliorated insulin action on hepatic gluconeogenesis in liver cells, demonstrating the antilipolytic activity contributed to ESMW beneficial effects on hepatic glucose production. In conclusion, ESMW, as the antilipolytic fraction of SMW, inhibited PKA-HSL related lipolysis by activating AMPK, thus inhibiting diacylglycerol (DAG) accumulation in the liver and thereby improving insulin resistance and hepatic gluconeogenesis.

Identification of a new azoreductase driven prodrug from bardoxolone methyl and 5-aminosalicylate for the treatment of colitis in mice.

For local treatment of ulcerative colitis, a new azoreductase driven prodrug CDDO-AZO from bardoxolone methyl (CDDO-Me) and 5-aminosalicylate (5-ASA) was designed, synthesized and biologically evaluated. It is proposed that orally administrated CDDO-AZO is stable before reaching the colon, while it can also be triggered by the presence of azoreductase in the colon to fragment into CDDO-Me and 5-ASA, generating potent anti-colitis effects. Superior to olsalazine (OLS, a clinically used drug for ulcerative colitis) and CDDO-Me plus 5-ASA, CDDO-AZO significantly attenuated inflammatory colitis symptoms in DSS-induced chronic colitis mice, which suggested that CDDO-AZO may be a promising anti-ulcerative colitis agent.

Antifungal Activity and Possible Mode of Action of Ningnanmycin Against Tea Gray Blight Disease Pathogen Pseudopestalotiopsis camelliae-sinensis.

Gray blight is a serious disease of tea (Camellia sinensis) for which there is currently no effective control or preventive measure apart from fungicides. Screening for effectiveness of a natural antimicrobial against this pathogen and identifying its mode of action could contribute to the management of this disease. Antifungal activity of the antimicrobial ningnanmycin (NNM) from Streptomyces noursei var. xichangensis against the pathogen causing gray blight disease, Pseudopestalotiopsis camelliae-sinensis strain GZHS-2017-010, was confirmed in vitro by the mycelial growth rate method. Optical microscopy, scanning electron microscopy, and transmission electron microscopy were used to observe morphological changes in hyphae of P. camelliae-sinensis treated with NNM. RNA sequencing, bioinformatics, and quantitative real-time PCR were used to identify genes in the hyphae that were differentially expressed in response to treatment with NNM. Thirty-eight genes from 16 pathways, known as targets of antifungal agents, were used to investigate gene expression in hyphae at the half-maximal effective concentration (EC50), EC30, and EC70 for 1, 7, or 14 h. The results indicated that NNM can inhibit the growth of hyphae in vitro, with an EC50 of 75.92 U/ml, inducing morphological changes in organelles, septa, and extracellular polysaccharides, targeting ribosomes to disturb translation in protein synthesis and influencing some biosynthetic functions of the hyphae.

UHPLC-qMS spectrum-effect relationships for Rhizoma Paridis extracts.

Rhizoma Paridis (RP) with significant anti-tumor and haemostatic effects, has been used as the raw material of many Traditional Chinese preparations. However, its active ingredients are still unclear. The present study aimed to discover bioactive ingredients from RP based on spectrum-relationship and chemometric methods. Firstly, the saponins extract was prepared by phytochemical methods. Furthermore, UHPLC-QTOF-MS and UHPLC-qMS were incorporated to establish an efficient and sensitive method for obtaining the chemical profiles of RP. A total of 34 saponins were characterized in RP and 13 of them were assigned as common peaks in 25 batches of samples. After evaluation of the anti-tumor and haemostatic activities of samples, spectrum-effect relationships were investigated by the grey relational analysis (GRA), orthogonal projections to latent structures (OPLS) and back propagation artificial neural network (BP-ANN). These analyses showed that polyphyllin VII (P27), polyphyllin II (P30), dioscin (P31) and polyphyllin I (P33) play a role in the haemostatic effects of RP whereas polyphyllin VII (P27), dioscin (P31), polyphyllin I (P33), progenin III (P34) were assigned as candidate ingredients accounting for the anti-tumor activity of RP. The anti-tumor and haemostatic activities of these screened ingredients were subsequently verified in vitro. Collectively, the present study established the spectrum-effect relationship mode of RP and discovered the bioactive compounds of RP, which could be also used for exploration of bioactive compounds in herbal medicines, especially for trace compounds.

Chemical profile of Xian-He-Cao-Chang-Yan formula and its effects on ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Xian-He-Cao-Chang-Yan formula (XHCF) is consisting of six crude drugs including Agrimoniae Herba, Coptidis Rhizoma, Aucklandiae Radix, Cicadae Periostracum, Acori Tatarinowii Rhizoma, and Platycodonis Radix at the ratio of 5:1.5:1.5:1.5:1.5:1. It has been used to improve syndromes of ulcerative colitis (UC) for many years. AIM OF THE STUDY: This study was designed to study the bioactive ingredients and therapeutic mechanisms of XHCF. MATERIALS AND METHODS: The chemical profile of XHCF was characterized by UHPLC-QTOF-MS/MS. The effects and mechanisms of XHCF on UC were investigated in colitis mice induced by dextran sulfate sodium (DSS) and LPS-stimulated RAW 264.7 cells. RESULTS: A total of 103 compounds were characterized in XHCF. XHCF could effectively improve acute colitis induced by DSS. More importantly, XHCF significantly decreased M1 macrophage markers (CD11c, IL-6 and IL-1ß) whereas increased M2 macrophage markers (CD206) in colitis mice, suggesting it could regulate macrophage polarization. Furthermore, the levels of HK2 and lactic acid in colon tissues were significantly reduced by XHCF, indicating that XHCF could inhibit glycolysis. It also down-regulated HK2 expression in macrophages challenged by LPS. In addition, XHCF enhanced the phosphorylation of AMPK both in vivo and in vitro, suggesting the involvement of AMPK in XHCF function. CONCLUSIONS: XHCF ameliorated DSS-induced colitis in mice via inhibition of M1 macrophage polarization, probably by the modulation of macrophage metabolic reprogramming via AMPK, contributing to its anti-inflammatory activity. The synergistic actions of multiple ingredients might be responsible for the therapeutic benefits of XHCF on UC.

Study on the hepatobiliary behavior of Ermiao wan formula by microdialysis- LC-qTOF-MS.

An improved bile microdialysis sampling technique was established and coupled with liquid chromatography quadrupole time-of-flight mass spectrometry (LC-qTOF-MS) analysis. This method was successfully applied to investigate the metabolic profiles of Ermiao wan (EMW) formula in the bile of Sprague-Dawley (SD) rats. Based on accurate mass information and fragment patterns, 23 alkaloids and lactones metabolites were tentatively identified. Their metabolic pathway involved in glucuronidation, sulfation, hydroxylation and hydrolysis. Because of the high time resolution of microdialysis, the metabolic profiles of EMW were also investigated. Jatrorrhizine, columbamine and other components showed a "double-peak" profiles, suggesting the existence of enterohepatic circulation. The developed microdialysis sampling/ LC-qTOF-MS method provides a simple and efficient research tool for understanding and clarifying the mechanism of hepatobiliary excretion of complex components.

Ilexgenin A prevents early colonic carcinogenesis and reprogramed lipid metabolism through HIF1α/SREBP-1.

BACKGROUND: Ilexgenin A (IA), the main bioactive compound from Ilex hainanensis Merr., has significant hypolipidemic activities. However, the effects of IA on colitis-associated colorectal cancer (CRC) and its mechanisms are still unknown. PURPOSE: The study was designed to evaluate the effect of IA on CRC and explore its underlying mechanisms. STUDY DESIGN: The effect of IA on colitis related CRC were evaluated in azoxymethane (AOM)/dextran sulfate sodium (DSS) mice and the underlying mechanisms were revealed by metabolomics, which were further validated in vivo and in vitro. METHODS: The Balb/c mice were treated with AOM/DSS to induce CRC model and fed with normal diet with or without 0.02% IA. After the experimental period, samples of plasma were collected and analyzed by ultra-high-performance liquid chromatography/quadrupole time off light mass spectrometry (UHPLC-Q-TOF). Multivariate statistical tools were used to identify the changes of serum metabolites associated with CRC and responses to IA treatment. HT 29 and HCT 116 cells were stimulated by palmitate (PA) and cultured under hypoxia. Western blot, Q-PCR, and Immunofluorescence staining were performed to confirm the molecular pathway in vivo and in vitro. RESULTS: Our results showed IA significantly inhibited the inflammatory colitis symptoms such as disease activity index score, shortening of colon tissues and the increase of inflammatory cytokines. In metabolomic study, 31 potential metabolites associated with CRC were identified and 24 of them were reversed by IA treatment. Most of biomarkers were associated with arachidonic acid metabolism, glycerophospholipid catabolism, and phospholipid metabolism, suggesting lipid metabolism might be involved in the beneficial effect of IA on CRC. Furthermore, we also found IA could decrease the expressions of SREBP-1 and its target gene in the colon tissues of AOM/DSS mice. It could down-regulate the triglyceride (TG) content and the expressions of HIF1α, SREBP-1, FASN, and ACC in HT 29 and HCT 116 cells. The inhibitory effect of IA on SREBP-1 was also attenuated by desferrioxamine (DFX), suggesting HIF1α is involved in the regulation of IA on SREBP-1. CONCLUSION: IA prevents early colonic carcinogenesis in AOM/DSS mice and reprogramed lipid metabolism partly through HIF1α/SREBP-1.

Ilexgenin A enhances the effects of simvastatin on non-alcoholic fatty liver disease without changes in simvastatin pharmacokinetics.

Cardiovascular disease (CVD) is the most common cause of death in patients with non-alcoholic fatty liver disease (NAFLD). New therapeutic strategies which have the potential for slowing down the evolution of NAFLD and reducing CVD-related mortality are urgently needed. Statins are well recognized in the treatment of dyslipidemia, but their use in the treatment of NAFLD is limited due to the safety concerns. Ilexgenin A (IA) is one of the main bioactive compounds in 'Shan-lv-cha', an herbal tea commonly used in China. In the present study, we investigated the possible synergistic therapeutic effects of IA and simvastatin (SV) on NAFLD. IA or SV showed beneficial effects on the rats with NAFLD by lowering the liver weight, liver index and plasma levels of alanine aminotransferase and aspartate aminotransferase, regulating abnormal metabolism of lipids and ameliorating steatosis in liver. IA significantly enhanced the hypolipidemic and anti-inflammation effects of SV. Furthermore, a sensitive, accurate, convenient and reproducible LC-MS method was developed to investigate the effects of IA on the pharmacokinetics of SV. No significant changes were observed in pharmacokinetic parameters of SV and simvastatin hydroxy acid in the IA plus SV co-treated group in comparison with those in the group treated with SV alone. The mRNA levels and activity of CYP3A1 were not altered by IA. In conclusion, the results obtained from the present study should be helpful for further clinical application of SV and IA alone or in combination.

Naringenin reduces oxidative stress and improves mitochondrial dysfunction via activation of the Nrf2/ARE signaling pathway in neurons.

Oxidative stress and mitochondrial dysfunction are considered to be major contributing factors in the development and progression of many neurodegenerative diseases. Naringenin (NAR) is an abundant flavanone in the Citrus genus and has been found to exert antioxidant, anticarcinogenic and antimutagenic effects. However, the potential underlying mechanism of its antioxidant effects remains unclear. In the present study, the authors investigated the antioxidant effect of NAR on neurons in vitro. Neurons isolated from the brains of Sprague-Dawley rats were randomly divided into a control group, model group, NAR-L group, NAR-M group and NAR-H group. The model group received hypoxia and re-oxygenation treatment, and the NAR-L, NAR-M and NAR-H groups received 20, 40 and 80 µM NAR, respectively. The levels of reactive oxygen species (ROS) in each group were detected by chloromethyl-2',7'dichlorodihydro fluorescein diacetate staining, and differences in mitochondrial dysfunction were analyzed through measurement of mitochondrial membrane potential (∆ψm), adenine nucleotide translocase transport activity and adenine nucleotide levels. MTT and flow cytometry assays were also used to analyze cell proliferation and apoptosis, and the effects of NAR on the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway were investigated using small interfering RNA methods. The authors detected an increased accumulation of ROS in the model group, and high-dose NAR could significantly reduce the levels of ROS. Furthermore, NAR could improve mitochondrial dysfunction, as indicated by increased levels of high-energy phosphates, enhanced mitochondrial ANT transport activity and increased mitochondrial membrane potential. Moreover, NAR increased cell viability and decreased the rate of cell apoptosis. NAR also increased the expression of Nrf2 and its downstream target genes. These findings demonstrated that NAR could reduce oxidative stress and improve mitochondrial dysfunction via activation of the Nrf2/ARE signaling pathway in neurons.

Polyyne-Enriched Extract from Oplopanax elatus Significantly Ameliorates the Progression of Colon Carcinogenesis in ApcMin/+ Mice.

Colorectal cancer (CRC) is the third most common cancer in the world. Oplopanax elatus is widely used in traditional medicine. However, little is known about its pharmacological effects and bioactive compounds. We evaluated the effects of the polyyne-enriched extract from O. elatus (PEO) on the progression of colon carcinogenesis in ApcMin/+ mice. In addition, these effects were also investigated in HCT116 and SW480 cells. After PEO oral administration (0.2% diet) for 12 weeks, PEO significantly improved body weight changes and reduced the tumor burden and tumor multiplicity compared with the untreated mice. Meanwhile, western blot and immunohistochemistry results showed PEO significantly reduced the expression of ß-catenin and cyclinD1 in both small intestine and the colon tissues compared with the untreated mice. In addition, PEO treatment significant decreased the cell viability in both HCT116 and SW480 cell lines. It also decreased the levels of ß-catenin, cyclinD1, c-myc and p-GSK-3ß in HCT116 and SW480 cells at 25 µM. These results indicate that PEO may have potential value in prevention of colon cancer by down-regulating Wnt-related protein.

Triterpenoids-Enriched Extract from the Aerial Parts of Salvia miltiorrhiza Regulates Macrophage Polarization and Ameliorates Insulin Resistance in High-Fat Fed Mice.

Adipose tissue inflammation and macrophage polarization are tightly associated with the development of obesity-associated insulin resistance. Our previous studies have demonstrated the triterpenoids-enriched extract from the aerial parts of Salvia miltiorrhiza (TTE) could significantly improve atherosclerosis in LDLR-/- mice. However, its molecular mechanisms of TTE ameliorating insulin resistance remain unclear. In the present study, obesity model with insulin resistance induced by feeding high-fat diet (HFD) was established. Dietary TTE attenuated hyperlipidemia, improved glucose intolerance in mice and mediated the activation of IRS-1/PI3K/Akt insulin signaling pathway. Meanwhile, dietary TTE also attenuated macrophage infiltrations into adipose tissue and modified the phenotype ratio of M1/M2 macrophages. Furthermore, our results showed that TTE regulated the polarization of macrophages partly via adenosine monophosphate-activated kinase (AMPK). Taken together, these findings suggested that TTE has a potential clinical utility in improving insulin resistance. Its mechanisms might be contributed to its beneficial effects on macrophage polarization via AMPK. Copyright © 2016 John Wiley & Sons, Ltd.

Pharmacokinetic profiles of falcarindiol and oplopandiol in rats after oral administration of polyynes extract of Oplopanax elatus.

Polyynes, such as facarindiol (FAD) and oplopandiol (OPD), are responsible for anticancer activities of Oplopanax elatus (O. elatus). A novel approach to pharmacokinetics determination of the two natural polyynes in rats was developed and validated using a liquid chromatography-electrospray ionization-mass spectrometry (LC-MS) method. Biosamples were prepared by liquid-liquid extraction using ethyl acetate/n-hexane (V : V = 9 : 1) and the analytes were eluted on an Agilent ZORBAX Eclipse Plus C18 threaded column (4.6 mm × 50 mm, 1.8 µm) with the mobile phase of acetonitrile-0.1% aqueous formic acid at a flow-rate of 0.5 mL·min(-1) within a total run time of 11 min. All analytes were simultaneously monitored in a single-quadrupole mass spectrometer in the selected ion monitoring (SIM) mode using electrospray source in positive mode. The method was demonstrated to be rapid, sensitive, and reliable, and it was successfully applied to the pharmacokinetic studies of the two polyynes in rat plasma after oral administration of polyynes extract of O. elatus.

American Ginseng Attenuates Colitis-Associated Colon Carcinogenesis in Mice: Impact on Gut Microbiota and Metabolomics.

Inflammatory bowel disease is a risk factor for colorectal cancer initiation and development. In this study, the effects of American ginseng on chemically induced colitis and colon carcinogenesis were evaluated using an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model. During the acute phase on day 15, the oral administration of ginseng (15 and 30 mg/kg/day) significantly suppressed AOM/DSS-induced colitis, as demonstrated by the disease activity index and colon tissue histology. During the chronic phase in week 13, AOM/DSS-induced tumor multiplicity was significantly suppressed by ginseng. Ginseng significantly attenuated the increase of inflammatory cytokines, such as IL1α, IL1ß, IL6, G-CSF, and GM-CSF. Serum metabolomics data in the PCA plots showed good separation between the AOM/DSS model and ginseng-treated mice, and the most important endogenous metabolite changes were identified. The 16S rRNA data showed that after AOM/DSS, the microbiome community in the model group was obviously changed, and ginseng inhibited these changes. Fecal metabolomics analysis supported these findings. In conclusion, oral ginseng significantly decreased AOM/DSS-induced colitis and colon carcinogenesis by inhibiting inflammatory cytokines and restoring the metabolomics and microbiota profiles accordingly. Selective endogenous small molecules could be used as biomarkers to elucidate the effects of ginseng treatment. Cancer Prev Res; 9(10); 803-11. ©2016 AACR.

Corosolic acid inhibits adipose tissue inflammation and ameliorates insulin resistance via AMPK activation in high-fat fed mice.

BACKGROUND: Adipose tissue inflammation is tightly associated with the development of insulin resistance. Corosolic acid (CRA), a natural triterpenoid, is well known as "phyto-insulin" due to its insulin-like activities. However, its underlying mechanism remains unknown. PURPOSE: In this study, we investigated the mechanisms of CRA on improving insulin resistance both in vivo and in vitro. METHODS: C57BL/6 mice were fed with normal diet, high-fat diet (HFD) or HFD with CRA, respectively. General biochemical parameters in blood and glucose intolerance in mice were assayed. Meanwhile, proinflammatory cytokines and macrophage infiltrations in adipose tissues were analyzed by real-time PCR and immunohistochemical staining. The effects of CRA on insulin signaling transduction and AMPK activity in adipose tissues were investigated by western blot. Furthermore, the effects of CRA on AMPK were confirmed on 3T3-L1 cells by using both AMPK inhibitor and AMPKα1/2-specific siRNA RESULTS: CRA attenuated hyperlipidemia, improved insulin sensitivity and glucose intolerance in mice. Meanwhile, it alleviated inflammation in adipose tissues, demonstrated by the suppression of IKKß phosphorylation and down-regulation of gene expressions of proinflammatory cytokines. Histological analysis revealed that CRA attenuated macrophage infiltrations into adipose tissue. It also improved insulin signaling transduction by modification of Ser/Thr phosphorylation of IRS-1 and downstream Akt, thereby improved insulin sensitivity in HFD-fed mice. Furthermore, CRA regulated AMPK activation in a LKB1-dependent manner. AMPKα knockdown in adipocytes abolished the inhibitory effects of CRA on IKKß and IRS-1 serine phosphorylation, indicating that CRA inhibited inflammation and ameliorated insulin resistance via AMPK activation. CONCLUSIONS: CRA inhibited inflammation with improvement in adipose tissue dysfunction and ameliorated insulin resistance in an AMPK-dependent manner.