Brevilin A exerts anti-colorectal cancer effects and potently inhibits STAT3 signaling invitro.

Colorectal cancer (CRC) is the third most common cause of cancer-related morbidity worldwide, with an estimated of 1.85 million new cases and 850,000 deaths every year. Nevertheless, the current treatment regimens for CRC have many disadvantages, including toxicities and off-targeted side effects. STAT3 (signal transducer and activator of transcription 3) has been considered as a promising molecular target for CRC therapy. Brevilin A, a sesquiterpene lactone compound rich in Centipedae Herba has potent anticancer effects in nasopharyngeal, prostate and breast cancer cells by inhibiting the STAT3 signaling. However, the anti-CRC effect of brevilin A and the underlying mechanism of action have not been fully elucidated. In this study, we aimed to investigate the involvement of STAT3 signaling in the anti-CRC action of brevilin A. Here, HCT-116 and CT26 cell models were used to investigate the anti-CRC effects of brevilin A in vitro. HCT-116 cells overespressing with STAT3 were used to evaluate the involvement of STAT3 signaling in the anti-CRC effect of brevilin A. Screening of 49 phosphorylated tyrosine kinases in the HCT-116 cells after brevilin A treatment was performed by using the human phospho-receptor tyrosine kinase (phospho-RTK) array. Results showed that brevilin A inhibited cell proliferation and cell viability, induced apoptosis, reduced cell migration and invasion, inhibited angiogenesis, lowered the protein expression levels of phospho-Src (Tyr416), phospho-JAK2 (Y1007/1008) and phospho-STAT3 (Tyr705), and inhibited STAT3 activation and nuclear localization. Brevilin A also significantly reduced the protein expression levels of STAT3 target genes, such as MMP-2, VEGF and Bcl-xL. More importantly, over-activation of STAT3 diminished brevilin A's effects on cell viability. All these results suggest that brevilin A exerts potent anti-CRC effects, at least in part, by inhibiting STAT3 signaling. Our findings provide a strong pharmacological basis for the future exploration and development of brevilin A as a novel STAT3-targeting phytotherapeutic agent for CRC treatment.

Therapeutic effects of Siegesbeckia orientalis L. and its active compound luteolin in rheumatoid arthritis: network pharmacology, molecular docking and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a common difficult disease with a high disability rate. Siegesbeckia orientalis L. (SO), a Chinese medicinal herb that is commonly used for treating RA in clinical practice. While, the anti-RA effect and the mechanisms of action of SO, as well as its active compound(s) have not been elucidated clearly. AIM OF THE STUDY: We aim to explore the molecular mechanism of SO against RA by using network pharmacology analysis, as well as the in vitro and in vivo experimental validations, and to explore the potential bioactive compound(s) in SO. METHODS: Network pharmacology is an advanced technology that provides us an efficient way to study the therapeutic actions of herbs with the underlying mechanisms of action delineated. Here, we used this approach to explore the anti-RA effects of SO, and then the molecular biological approaches were used to verify the prediction. We first established a drug-ingredient-target-disease network and a protein-protein interaction (PPI) network of SO-related RA targets, followed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Further, we used lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and vascular endothelial growth factor-A (VEGFA)-induced human umbilical vein endothelial cell (HUVEC) models, as well as adjuvant-induced arthritis (AIA) rat model to validate the anti-RA effects of SO. The chemical profile of SO was also determined by using the UHPLC-TOF-MS/MS analysis. RESULTS: Network pharmacology analysis highlighted inflammatory- and angiogenesis-related signaling pathways as promising pathways that mediate the anti-RA effects of SO. Further, in both in vivo and in vitro models, we found that the anti-RA effect of SO is at least partially due to the inhibition of toll like receptor 4 (TLR4) signaling. Molecular docking analysis revealed that luteolin, an active compound in SO, shows the highest degree of connections in compound-target network; moreover, it has a direct binding to the TLR4/MD-2 complex, which is confirmed in cell models. Besides, more than forty compounds including luteolin, darutoside and kaempferol corresponding to their individual peaks were identified tentatively via matching with the empirical molecular formulae and their mass fragments. CONCLUSION: We found that SO and its active compound luteolin exhibit anti-RA activities and potently inhibit TLR4 signaling both in vitro and in vivo. These findings not only indicate the advantage of network pharmacology in the discovery of herb-based therapeutics for treating diseases, but also suggest that SO and its active compound(s) could be developed as potential anti-RA therapeutic drugs.

Brevilin A is a potent anti-metastatic CRC agent that targets the VEGF-IL6-STAT3 axis in the HSCs-CRC interplay.

BACKGROUND: More than half of the colorectal cancer (CRC) patients will develop liver metastasis that underlies the cancer mortality. In the hepatic tumor microenvironment, the interplay between CRC cells and hepatic stellate cells (HSCs), and the activation of HSCs to become carcinoma-associated fibroblasts (CAFs) will further promote the cancer development. Nevertheless, the critical signaling molecule that involved in these processes remains unknown, which hinders the development of effective therapeutic agents for the treatment of metastatic CRC (mCRC). METHODS: Conditioned medium system and co-cultured system were used to examine the interplay between CRC cells and HSCs. Luminex liquid suspension chip detection and enzyme-linked immunosorbent assay were used to screen for the mediators in the conditioned medium that facilitated the CRC-HSCs interplay and HSCs-to-CAFs differentiation. Cell and animal models were used to examine whether brevilin A inhibited CRC liver metastasis via the VEGF-IL6-STAT3 axis. RESULTS: In the CRC-HSCs interplay, CRC promoted HSCs-to-CAFs differentiation by releasing vascular endothelial growth factor (VEGF); and HSCs released interleukin 6 (IL6) that activated signal transducer and activator of transcription 3 (STAT3) in the CRC and hence increased the cancer metastatic potential. The functions of the VEGF-IL6-STAT3 axis in the HSCs-CRC interplay were further validated by VEGF recombinant protein and IL6 neutralizing antibody. More importantly, brevilin A, an active compound isolated from Centipeda minima (L.) A. Br. et Aschers, targeted the VEGF-IL6-STAT3 axis in the CRC-HSCs interplay, hence significantly inhibited colorectal liver metastasis and cancer growth both in vitro and in vivo. CONCLUSIONS: We are the first to demonstrate brevilin A possesses potent anti-mCRC effect by targeting the VEGF-IL6-STAT3 axis in the CRC-HSCs interplay. Our findings not only support the development of brevilin A as a novel therapeutic agent for mCRC treatment, but also pave the path for the development of other VEGF-IL6-STAT3 targeting therapeutic strategies.

Fucoxanthin Is a Potential Therapeutic Agent for the Treatment of Breast Cancer.

Breast cancer (BC) is one of the most common cancers diagnosed and the leading cause of cancer-related death in women. Although there are first-line treatments for BC, drug resistances and adverse events have been reported. Given the incidence of BC keeps increasing, seeking novel therapeutics is urgently needed. Fucoxanthin (Fx) is a dietary carotenoid commonly found in seaweeds and diatoms. Both in vitro and in vivo studies show that Fx and its deacetylated metabolite fucoxanthinol (Fxol) inhibit and prevent BC growth. The NF-κB signaling pathway is considered the major pathway contributing to the anti-proliferation, anti-angiogenesis and pro-apoptotic effects of Fx and Fxol. Other signaling molecules such as MAPK, MMP2/9, CYP and ROS are also involved in the anti-cancer effects by regulating the tumor microenvironment, cancer metastasis, carcinogen metabolism and oxidation. Besides, Fx also possesses anti-obesity effects by regulating UCP1 levels and lipid metabolism, which may help to reduce BC risk. More importantly, mounting evidence demonstrates that Fx overcomes drug resistance. This review aims to give an updated summary of the anti-cancer effects of Fx and summarize the underlying mechanisms of action, which will provide novel strategies for the development of Fx as an anti-cancer therapeutic agent.

miR-7/TGF-ß2 axis sustains acidic tumor microenvironment-induced lung cancer metastasis.

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-ß2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-ß2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-ß2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-ß2; the expressions of both miR-7-5p and TGF-ß2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-ß2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.

Cell death mechanisms induced by synergistic effects of halofuginone and artemisinin in colorectal cancer cells.

Our previous study found that the combination of halofuginone (HF) and artemisinin (ATS) synergistically arrest colorectal cancer (CRC) cells at the G1/G0 phase of the cell cycle; however, it remains unclear whether HF-ATS induces cell death. Here we report that HF-ATS synergistically induced caspase-dependent apoptosis in CRC cells. Specifically, both in vitro and in vivo experiments showed that HF or HF-ATS induces apoptosis via activation of caspase-9 and caspase-8 while only caspase-9 is involved in ATS-induced apoptosis. Furthermore, we found HF or HF-ATS induces autophagy; ATS can't induce autophagy until caspase-9 is blocked. Further analyzing the crosstalk between autophagic and caspase activation in CRC cells, we found autophagy is essential for activation of caspase-8, and ATS switches to activate capase-8 via induction of autophagy when caspase-9 is inhibited. When apoptosis is totally blocked, HF-ATS switches to induce autophagic cell death. This scenario was then confirmed in studies of chemoresistance CRC cells with defective apoptosis. Our results indicate that HF-ATS induces cell death via interaction between apoptosis and autophagy in CRC cells. These results highlight the value of continued investigation into the potential use of this combination in cancer therapy.

Chinese Medicinal Herbs Targeting the Gut-Liver Axis and Adipose Tissue-Liver Axis for Non-Alcoholic Fatty Liver Disease Treatments: The Ancient Wisdom and Modern Science.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. The pathogenesis of NAFLD is complex. Frontline western medicines only ameliorate the symptoms of NAFLD. On the contrary, the uniqueness of Chinese medicine in its interpretation of NAFLD and the holistic therapeutic approach lead to a promising therapeutic efficacy. Recent studies reveal that the gut-liver axis and adipose tissue-liver axis play important roles in the development of NAFLD. Interestingly, with advanced technology, many herbal formulae are found to target the gut-liver axis and adipose tissue-liver axis and resolve the inflammation in NAFLD. This is the first review summarizes the current findings on the Chinese herbal formulae that target the two axes in NAFLD treatment. This review not only demonstrates how the ancient wisdom of Chinese medicine is being interpreted by modern pharmacological studies, but also provides valuable information for the further development of the herbal-based treatment for NAFLD.

Resveratrol Stimulates the Na+-Ca2+ Exchanger on the Plasma Membrane to Reduce Cytosolic Ca2+ in Rat Aortic Smooth Muscle Cells.

Resveratrol is well known to exhibit vascular relaxant and antihypertensive effects. In this study, we determined the effects of resveratrol on the modulation of cytosolic [Ca] level and adenosine 5'-triphosphate-induced Ca release from the sarcoplasmic reticulum (SR) in rat aortic smooth muscle cells (ASMCs) and explored its underlying mechanisms. In this article, cytosolic [Ca] and SR [Ca] in ASMCs were determined by Fluo-4/acetoxymethyl and Mag-Fluo-4/acetoxymethyl respectively. Resveratrol (20, 50, and 100 µM) caused a rapid and substantial reduction in cytosolic [Ca] in ASMCs bathed in normal Hank's Balanced Salt Solution or Ca-free Hank's Balanced Salt Solution. Pretreatment with resveratrol reduced adenosine 5'-triphosphate-induced SR Ca release and SR Ca content. In the cells bathed in Na-free physiological saline, which favors the reverse mode of the Na-Ca exchanger (NCX), resveratrol induced an increase in cytosolic [Ca] and SR [Ca]. However, its effect on cytosolic [Ca] was inhibited by the selective NCX inhibitor, SEA0400. Our findings suggest that resveratrol reduces cytosolic [Ca] and SR [Ca] in ASMCs in normal physiological saline, which might be, at least in part, mediated by the NCX.

Silibinin Promotes Cell Proliferation Through Facilitating G1/S Transitions by Activating Drp1-Mediated Mitochondrial Fission in Cells.

Heart, liver, and kidney, which are known as the essential organs for metabolism, possess the unique ability to regulate the proliferation function of the body against injury. Silibinin (SB), a natural polyphenolic flavonoid extracted from traditional herb Silybum marianum L., has been used to protect hepatocytes. Whether SB can regulate mitochondrial fission in normal cells and the underlying mechanisms remain unclear. Here, we showed that SB markedly promoted cell proliferation by facilitating G1/S transition via activating dynamin-related protein 1 (Drp1), which in turn mediated mitochondrial fission in these normal cells. SB dose-dependently increased the mitochondrial mass, mtDNA copy number, cellular adenosine triphosphate production, mitochondrial membrane potential, and reactive oxygen species in normal cells. Furthermore, SB dose-dependently increased the expression of Drp1. Blocking Drp1 abolished SB-induced mitochondrial fission. In conclusion, we demonstrate that SB promotes cell proliferation through facilitating G1/S transition by activating Drp1-mediated mitochondrial fission. This study suggests that SB is a potentially useful herbal derivative for the daily prevention of various diseases caused by impaired mitochondrial fission.

Silibinin Induces G2/M Cell Cycle Arrest by Activating Drp1-Dependent Mitochondrial Fission in Cervical Cancer.

Cervical cancer is the fourth leading cancer type and the second most common gynecological malignancy among women worldwide. Silibinin (SB), a chief bioactive natural polyphenolic flavonoid of Silybum marianum L., has been used clinically for its hepatocyte protective effects. It also has anticancer effects via the induction of apoptosis and cell cycle arrest. However, the effects of SB on cervical cancer cells through mitochondrial fission have not been studied. Here, we showed that SB markedly suppressed cervical cell proliferation by inducing G2/M cell cycle arrest via the activation of dynamin-related protein 1 (Drp1), which in turn mediated the mitochondrial fission dysfunction both in vitro and in vivo. SB decreased the ATP content, mitochondrial membrane potential, and mtDNA copy number, as well as reduced the reactive oxygen species levels in cervical cells. Furthermore, SB induced excessive mitochondrial fragmentation and reduced tubule formation. Further study showed that knockdown of Drp1 abolished the SB-induced G2/M cell cycle arrest in cervical cancer cells by inhibiting the mitochondrial fission pathway. More importantly, SB inhibited Hela cell growth in vivo model. In conclusion, we are the first to demonstrate that SB induces cervical cancer cell G2/M cell cycle arrest by activating Drp1-dependent mitochondrial fission dysfunction. This study suggests the strategy of inducing Drp1-dependent mitochondrial fission for cervical cancer prevention and treatment.

Saturated long-chain fatty acid-producing bacteria contribute to enhanced colonic motility in rats.

BACKGROUND: The gut microbiota is closely associated with gastrointestinal (GI) motility disorder, but the mechanism(s) by which bacteria interact with and affect host GI motility remains unclear. In this study, through using metabolomic and metagenomic analyses, an animal model of neonatal maternal separation (NMS) characterized by accelerated colonic motility and gut dysbiosis was used to investigate the mechanism underlying microbiota-driven motility dysfunction. RESULTS: An excess of intracolonic saturated long-chain fatty acids (SLCFAs) was associated with enhanced bowel motility in NMS rats. Heptadecanoic acid (C17:0) and stearic acid (C18:0), as the most abundant odd- and even-numbered carbon SLCFAs in the colon lumen, can promote rat colonic muscle contraction and increase stool frequency. Increase of SLCFAs was positively correlated with elevated abundances of Prevotella, Lactobacillus, and Alistipes. Functional annotation found that the level of bacterial LCFA biosynthesis was highly enriched in NMS group. Essential synthetic genes Fabs were largely identified from the genera Prevotella, Lactobacillus, and Alistipes. Pseudo germ-free (GF) rats receiving fecal microbiota from NMS donors exhibited increased defecation frequency and upregulated bacterial production of intracolonic SLCFAs. Modulation of gut dysbiosis by neomycin effectively attenuated GI motility and reduced bacterial SLCFA generation in the colon lumen of NMS rats. CONCLUSIONS: These findings reveal a previously unknown relationship between gut bacteria, intracolonic SLCFAs, and host GI motility, suggesting the importance of SLCFA-producing bacteria in GI motility disorders. Further exploration of this relationship could lead to a precise medication targeting the gut microbiota for treating GI motility disorders.

Cell imaging of dopamine receptor using agonist labeling iridium(iii) complex.

Dopamine receptor expression is correlated with certain types of cancers, including lung, breast and colon cancers. In this study, we report luminescent iridium(iii) complexes (11-14) as intracellular dopamine receptor (D1R/D2R) cell imaging agents. Complexes 11 and 13, which are conjugated with a dopamine receptor agonist, showed superior cell imaging characteristics, high stability and low cytotoxicity (>100 µM) in A549 lung cancer cells. siRNA knockdown and dopamine competitive assays indicated that complexes 11 and 13 could selectively bind to dopamine receptors (D1R/D2R) in A549 cells. Fluorescence lifetime microscopy demonstrated that complex 13 has a longer luminescence lifetime at the wavelength of 560-650 nm than DAPI and other chromophores in biological fluids. The long luminescence lifetime of complex 13 not only provides an opportunity for efficient dopamine receptor tracking in biological media, but also enables the temporal separation of the probe signal from the intense background signal by fluorescence lifetime microscopy for efficient analysis. Complex 13 also shows high photostability, which could allow it to be employed for long-term cellular imaging. Furthermore, complex 13 could selectively track the internalization process of dopamine receptors (D1R/D2R) in living cells. To the best of our knowledge, complex 13 is the first metal-based compound that has been used to monitor intracellular dopamine receptors in living cells.

The Role of Healthy Lifestyle in the Implementation of Regressing Suboptimal Health Status among College Students in China: A Nested Case-Control Study.

BACKGROUND: Suboptimal health status (SHS) is the intermediate health state between health and disease, it is medically undiagnosed and is also termed functional somatic syndrome. Although its clinical manifestations are complicated and various, SHS has not reached the disease status. Unhealthy lifestyle is associated with many chronic diseases and mortality. In accordance with the impact of lifestyle on health, it is intriguing to determine the association between unhealthy lifestyle and SHS risk. METHODS: We conducted a nested case-control study among healthy Chinese college students from March 2012 to September 2013, which was nested in a prospective cohort of 5676 students. We performed 1:1 incidence density sampling with matched controls for birth year, sex, grade, specialty and individual character. SHS was evaluated using the medical examination report and Sub-health Measurement Scale V1.0 (SHMS V1.0). Exposure was defined as an unhealthy lifestyle per the frequency of six behavioral dimensions from the Health-promoting Lifestyle Profile (HPLP-II). RESULTS: We matched 543 cases of SHS (42.66%) in a cohort of 1273 students during the 1.5 years mean follow-up time with controls. A significant difference (t = 9.79, p < 0.001) and a reduction in HPLP-II total score was present at 1.5 years follow-up (135.93 ± 17.65) compared to baseline (144.48 ± 18.66). A level-response effect was recorded with an increase of the total HPLP-II (every dimension was correlated with a decreased SHS risk). Compared to respondents with the least exposure (excellent level), those reporting a general HPLP-II level were approximately 2.3 times more likely to develop SHS (odd ratio = 2.333, 95% CI = 1.471 to 3.700); and those with less HPLP-II level (good level) were approximately 1.6 times more likely (1.644, 1.119-2.414) to develop SHS (p < 0.05). Our data indicated that unhealthy lifestyle behavior with respect to behavioral dimensions significantly affected SHS likelihood. Further analyses revealed a marked increase (average increased 14.73 points) in lifestyle level among those SHS regression to health after 1.5 years, with respect to the HPLP-II behavioral dimensions, in addition to the total score (t = -15.34, p < 0.001). CONCLUSIONS: SHS is highly attributable to unhealthy lifestyles, and the Int. J. Environ. Res. Public Health 2017, 14, 240 2 of 17 mitigation of modifiable lifestyle risk factors may lead to SHS regression. Increased efforts to modify unhealthy lifestyles are necessary to prevent SHS.

The effects of short-term high-fat feeding on exercise capacity: multi-tissue transcriptome changes by RNA sequencing analysis.

BACKGROUND: The effects of short-term high fat diets on physiology are elusive and the molecular changes following fat overconsumption remain largely unknown. In this study, we aimed to evaluate exercise capacity in mice fed with a high fat diet (HFD) for 3 days and investigate the molecular mechanisms in the early response to high-fat feeding. METHODS: Exercise capacity was assessed by weight-loaded swimming test in mice fed a control diet (10 kcal% fat) or a HFD (60 kcal% fat) for 3 days. Global gene expression of ten important tissues (brain, heart, liver, spleen, lung, kidney, stomach, duodenum, skeletal muscle and blood) was analyzed using RNA Sequencing. RESULTS: A HFD for just 3 days can induce 71% decrease of exercise performance prior to substantial weight gain (P <0.01). Principle component analysis revealed that differential gene expression patterns existed in the ten tissues. Out of which, the brain, spleen and lung were demonstrated to have more pronounced transcriptional changes than other tissues. Biological process analysis for differentially expressed genes in the brain, spleen and lung showed that dysregulation of peripheral and central immune response had been implicated in the early stage of HFD exposure. Neurotransmission related genes and circulatory system process related genes were significantly down-regulated in the brain and lung, respectively. CONCLUSIONS: Our findings provide new insights for the deleterious effects of high-fat feeding, especially revealing that the lung maybe as a new important target attacked by short-term high-fat feeding.

Sensitization of melanoma cells to alkylating agent-induced DNA damage and cell death via orchestrating oxidative stress and IKKß inhibition.

Nitrosourea represents one of the most active classes of chemotherapeutic alkylating agents for metastatic melanoma. Treatment with nitrosoureas caused severe systemic side effects which hamper its clinical use. Here, we provide pharmacological evidence that reactive oxygen species (ROS) induction and IKKß inhibition cooperatively enhance nitrosourea-induced cytotoxicity in melanoma cells. We identified SC-514 as a ROS-inducing IKKß inhibitor which enhanced the function of nitrosoureas. Elevated ROS level results in increased DNA crosslink efficiency triggered by nitrosoureas and IKKß inhibition enhances DNA damage signals and sensitizes nitrosourea-induced cell death. Using xenograft mouse model, we confirm that ROS-inducing IKKß inhibitor cooperates with nitrosourea to reduce tumor size and malignancy in vivo. Taken together, our results illustrate a new direction in nitrosourea treatment, and reveal that the combination of ROS-inducing IKKß inhibitors with nitrosoureas can be potentially exploited for melanoma therapy.

Comparative evaluation of chemical profiles of three representative 'snow lotus' herbs by UPLC-DAD-QTOF-MS combined with principal component and hierarchical cluster analyses.

Herbal healthcare products are used worldwide as relatively safe and effective alternatives to allopathic drugs. Saussurea laniceps Hand.-Mazz. (SL), S. medusa Maxim. (SM) and S. involucrata (Kar. et Kir.) Sch.Bip. (SI) are three sources of the renowned 'snow lotus', Chinese materia medica for treating inflammatory diseases. The three species have different therapeutic effects, among which SL has been proved to be the most potent, but they are frequently confused on the market and in the academic community. An ultra-high performance liquid chromatography-diode array detector-quadrupole time of flight-mass spectrometry (UPLC-DAD-QTOF-MS) method was developed and used to analyze 49 herbal samples for species analysis and overall quality evaluation. With 25 simultaneously identified constituents, of which 12 were quantified, the three herbs showed different chemical profiles. Four-dimensional principle component analysis (4D-PCA) and orthogonal hierarchical cluster analysis (2D-HCA) results illustrated that SL should be grouped away from SM and SI, contradicting the botanical record in Flora of China. The present chemical determination and pattern recognition results directly explain the therapeutic potency of SL and distinguish the three confused snow lotus herbs. Furthermore, the findings suggest a possible extensive quality evaluation model for multi-origin medicinal plants and help monitor falsification of snow lotus herbal products on the market, contributing to a more regulated pharmaceutical industry. Copyright © 2016 John Wiley & Sons, Ltd.

The Role of Stress Management in the Relationship between Purpose in Life and Self-Rated Health in Teachers: A Mediation Analysis.

BACKGROUND: To examine whether stress management mediates the relationship between purpose in life and self-rated health status (SRH). METHODS: A cross-sectional survey was conducted among 6840 teachers in 2013 in Guangzhou, China. Purpose in life was assessed through the Purpose in Life Subscale of the Psychological Well-being Scale. Stress management was assessed using the eight-item questionnaire adapted from the Health-promoting Lifestyle Profile II. SRH was assessed by the Suboptimal Health Measurement Scale Version 1.0. The mediation hypothesis was tested by the structural equation model for path analysis. RESULTS: It was found that purpose in life had direct and indirect effects on SRH. The path analysis showed the total effect (ß = 0.563) of purpose in life on SRH was comprised of a direct effect (ß = 0.319) and an indirect effect (ß = 0.244), which was mediated by stress management. CONCLUSIONS: By supporting the mediation hypothesis, our results indicate that stress management mediated the effect of purpose in life on SRH. Enhancement of teachers' purpose in life and improvement of training skills of stress management should be incorporated in the strategy of improving teachers' health.

Work-Recreation Balance, Health-Promoting Lifestyles and Suboptimal Health Status in Southern China: A Cross-Sectional Study.

Suboptimal health status (SHS)-an intermediate state between health and illness--refers to functional somatic symptoms that are medically undiagnosed. Although- SHS has become a great challenge for global public health, very little about its etiology and mechanisms are known. Work-recreation balance is a part of work-life balance, and is related to stress which greatly influences health status. We therefore carried out a cross-sectional investigation between 2012 and 2013 within a clustered sample of 24,475 individuals aged 15-60 years from a population in southern China. In so doing, we hoped to illuminate the associations between work-recreation balance conditions, healthy lifestyles, and SHS. Work-recreation balance conditions were categorically defined by frequency ("rarely, sometimes, or always"). Health-Promoting Lifestyle Profile (HPLP-II) was used to evaluate the level of healthy lifestyles, and the medical examination report and Sub-Health Measurement Scale V1.0 (SHMS V1.0) were both used to evaluate health status. The ratio of SHS (46.3%) is higher than health status (18.4%) or disease status (35.3%). Overall, 4.9% of respondents reported the lowest level of work-recreation balance, and they scored lower on both the HPLP-II and SHMS V1.0 compared with those who frequently maintained a work-recreation balance. Significant association was found between work-recreation balance behaviors and healthy lifestyles (p < 0.001) after demographic adjustment. In comparison with those reporting a frequent work-recreation balance, individuals whose work-recreation balance was categorically "rare" were 1.69 times as likely to develop SHS (odds ratio (OR): 1.69, 95% confidence interval (CI): 1.49-1.92), and those with infrequent work-recreation balance ("sometimes") were 1.71 times more likely to develop SHS (OR: 1.71, 95% CI: 1.62-1.81). These findings suggest that work-recreation balance conditions are significantly associated with, and seem to be accurate behavioral indicia of a healthy lifestyle. Poor work-recreation balance is associated with increased risk for SHS; thus, a healthier lifestyle that maintains a work-recreation balance should be promoted in order to reduce the development of SHS or disease in southern China.

Inhibition of the STAT3 signaling pathway contributes to apigenin-mediated anti-metastatic effect in melanoma.

Signal transducer and activator of transcription 3 (STAT3) signaling is constantly activated in human melanoma, and promotes melanoma metastasis. The dietary flavonoid apigenin is a bioactive compound that possesses low toxicity and exerts anti-metastatic activity in melanoma. However, the anti-metastasis mechanism of apigenin has not been fully elucidated. In the present study, we showed that apigenin suppressed murine melanoma B16F10 cell lung metastasis in mice, and inhibited cell migration and invasion in human and murine melanoma cells. Further study indicated that apigenin effectively suppressed STAT3 phosphorylation, decreased STAT3 nuclear localization and inhibited STAT3 transcriptional activity. Apigenin also down-regulated STAT3 target genes MMP-2, MMP-9, VEGF and Twist1, which are involved in cell migration and invasion. More importantly, overexpression of STAT3 or Twist1 partially reversed apigenin-impaired cell migration and invasion. Our data not only reveal a novel anti-metastasis mechanism of apigenin but also support the notion that STAT3 is an attractive and promising target for melanoma treatment.

A herbal formula comprising Rosae Multiflorae Fructus and Lonicerae Japonicae Flos, attenuates collagen-induced arthritis and inhibits TLR4 signalling in rats.

RL, a traditional remedy for Rheumatoid arthritis (RA), comprises two edible herbs, Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. We have reported that RL could inhibit the production of inflammatory mediators in immune cells. Here we investigated the effects and the mechanism of action of RL in collagen-induced arthritis (CIA) rats. RL significantly increased food intake and weight gain of CIA rats without any observable adverse effect; ameliorated joint erythema and swelling; inhibited immune cell infiltration, bone erosion and osteophyte formation in joints; reduced joint protein expression levels of TLR4, phospho-TAK1, phospho-NF-κB p65, phospho-c-Jun and phospho-IRF3; lowered levels of inflammatory factors (TNF-α, IL-6, IL-1ß, IL-17A and MCP-1 in sera and TNF-α, IL-6, IL-1ß and IL-17A in joints); elevated serum IL-10 level; reinvigorated activities of antioxidant SOD, CAT and GSH-Px in the liver and serum; reduced Th17 cell proportions in splenocytes; inhibited splenocyte proliferation and activation; and lowered serum IgG level. In conclusion, RL at nontoxic doses inhibited TLR4 signaling and potently improved clinical conditions of CIA rats. These findings provide further pharmacological justifications for the traditional use of RL in RA management.