High dietary intake of unsaturated fatty acids is associated with improved insulin resistance - a cross-sectional study based on the NHANES database.

BACKGROUND: A moderate intake of unsaturated fatty acids (UFA) is associated positively with improved insulin resistance. The aim of this study was to investigate the relationship between the dietary intake of unsaturated fatty acids/total fats (UFA/TF) and insulin resistance. METHODS: 15,560 participants were selected from the National Health and Nutrition Examination Survey (NHANES) database enrolled between March 2017 and 2020, and excluded those under 20 years of age, pregnant, or with missing data for key research items. Finally, 7,630 participants were included in the study. R software was used for data analysis that included: (1) general descriptive statistics; (2) comparison of differences in baseline information of three UFA/TF groups, namely low, medium, and high ratios; (3) calculation of the correlation between the UFA/TF ratio and markers of insulin resistance: triglyceride-glucose index (TyG) and homeostatic model assessment for insulin resistance (HOMA-IR); (4) stratification of the study subjects into two groups, with or without insulin resistance, using a cut-off value of HOMA-IR ≥ 2, followed by logistic regression analysis to examine the relationship between UFA/TF and insulin resistance status in the two groups; and (5) further stratification of the subjects according to age, gender, body mass index (BMI), race, total energy intake, total protein, total carbohydrate, total sugars, total dietary fiber, total fat, alcohol consumption, diabetes, hypercholesterolemia to analyze the impact of UFA/TF on insulin resistance status in different subgroups. RESULTS: (1) A high UFA/TF level was associated with a low TyG index and HOMA-IR [ß (vs. TyG index) = -0.559, 95% CI: (-0.821~-0.297), P < 0.001; ß (vs. HOMA-IR) = -0.742, 95% CI: (-1.083~-0.402), P < 0.001]. This negative relationship became more pronounced when UFA/TF exceeded 57.9% (i.e., the higher group). (2) Logistic regression analysis showed that a higher UFA/TF level was associated with a lower risk of developing insulin resistance [Q3 vs. Q1: 0.838 (95%CI: 0.709 ~ 0.991); P for trend = 0.038]. After adjusting for covariates such as gender, age, and BMI, this protective effect remained significant (P value < 0.05). (3) Analysis also showed that increased UFA/TF intake reduced the risk of developing insulin resistance (OR = 0.266, 95% CI: (0.075 ~ 0.946), P = 0.041). Subgroup analysis showed that although elevated UFA/TF intake showed no statistically significant difference in its effect in most subgroups, the large study population in this study provides valuable insights on potential changes. Increased UFA/TF intake may confer relatively greater benefits within specific subgroups, particularly among the elderly [Q3 age group, OR = 0.114, 95%CI: (0.012 ~ 1.078), P = 0.058], females [OR = 0.234, 95%CI: (0.041 ~ 1.333), P = 0.102], those with a BMI ≤ 25 kg/m²[OR = 0.191, 95%CI: (0.016 ~ 2.344), P = 0.196], and individuals without hypercholesterolemia [OR = 0.207, 95%CI: (0.042 ~ 1.013), P = 0.0519]. The impact of high UFA/TF levels within subgroups based on the presence or absence of coronary heart disease and stroke displayed contrasting trends. In those without coronary heart disease, there was a significant protective effect against insulin resistance [OR = 0.254, 95% CI: (0.07 ~ 0.929), P = 0.0384], while in the stroke subgroup, a significantly protective effect against insulin resistance was observed [OR = 0.002, 95%CI: (0 ~ 0.695), P = 0.0376]. CONCLUSION: A high dietary intake of UFA relative to total fat consumption could be a protective factor against the risk of developing insulin resistance.

Hydrogen sulfide alleviates heart failure with preserved ejection fraction in mice by targeting mitochondrial abnormalities via PGC-1α.

AIM: Increasing evidence has proposed that mitochondrial abnormalities may be an important factor contributing to the development of heart failure with preserved ejection fraction (HFpEF). Hydrogen sulfide (H2S) has been suggested to play a pivotal role in regulating mitochondrial function. Therefore, the present study was designed to explore the protective effect of H2S on mitochondrial dysfunction in a multifactorial mouse model of HFpEF. METHODS: Wild type, 8-week-old, male C57BL/6J mice or cardiomyocyte specific-Cse (Cystathionine γ-lyase, a major H2S-producing enzyme) knockout mice (CSEcko) were given high-fat diet (HFD) and l-NAME (an inhibitor of constitutive nitric oxide synthases) or standardized chow. After 4 weeks, mice were randomly administered with NaHS (a conventional H2S donor), ZLN005 (a potent transcriptional activator of PGC-1α) or vehicle. After additional 4 weeks, echocardiogram and mitochondrial function were evaluated. Expression of PGC-1α, NRF1 and TFAM in cardiomyocytes was assayed by Western blot. RESULTS: Challenging with HFD and l-NAME in mice not only caused HFpEF but also inhibited the production of endogenous H2S in a time-dependent manner. Meanwhile the expression of PGC-1α and mitochondrial function in cardiomyocytes were impaired. Supplementation with NaHS not only upregulated the expression of PGC-1α, NRF1 and TFAM in cardiomyocytes but also restored mitochondrial function and ultrastructure, conferring an obvious improvement in cardiac diastolic function. In contrast, cardiac deletion of CSE gene aggravated the inhibition of PGC-1α-NRF1-TFAM pathway, mitochondrial abnormalities and diastolic dysfunction. The deleterious effect observed in CSEcko HFpEF mice was partially counteracted by pre-treatment with ZLN005 or supplementation with NaHS. CONCLUSION: Our findings have demonstrated that H2S ameliorates left ventricular diastolic dysfunction by restoring mitochondrial abnormalities via upregulating PGC-1α and its downstream targets NRF1 and TFAM, suggesting the therapeutic potential of H2S supplementation in multifactorial HFpEF.

Multiple approaches to characterize and visualize the chemical composition of Sijunzi Decoction comprehensively.

Sijunzi Decoction is composed of Ginseng Radix et Rhizoma, Atractylodes Macrocephalae Rhizoma, Poria, and Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle, and it is a classic formula for treating spleen deficiency syndrome in Chinese medicine. Clarifying the active substances is an effective way to develop Traditional Chinese medicine and innovative medicines. Carbohydrates, proteins, amino acids, saponins, flavonoids, phenolic acids, and inorganic elements in the decoction were analyzed by multiple approaches. A molecular network was also used for visualizing the ingredients in Sijunzi Decoction, and representative components were also quantified. The detected components accounted for 74.544% of the Sijunzi Decoction freeze-dried powder, including 41.751% crude polysaccharides, 17.826% sugars (degree of polymerization 1-2), 8.181% total saponins, 2.427% insoluble precipitates, 2.154% free amino acids, 1.177% total flavonoids, 0.546% total phenolic acids, and 0.483% inorganic elements. Molecular network and quantitative analysis used to characterize the chemical composition of Sijunzi Decoction. The present study systematically characterized the constituents of Sijunzi Decoction, revealed the composition ratio of each type of constituent, and provided a reference for study on the substance basis of other Chinese medicine.

A mechanism of Sijunzi decoction on improving intestinal injury with spleen deficiency syndrome and the rationality of its compatibility.

ETHNOPHARMACOLOGICAL RELEVANCE: Sijunzi Decoction (SJZD) is a renowned formula for the treatment of spleen deficiency syndrome (SDS) in traditional Chinese medicine (TCM). Its non-polysaccharides (NPS) component, dominated by various compounds of SJZD, has shown the remarkable efficacy in SDS, especially in gastrointestinal injury. However, the principle of compatibility of SJZD and the micro-mechanism of effect on SDS are still unclear. AIM OF THE STUDY: To elucidate the scientific implications of SJZD compatibility and its micro-mechanism in the treatment of SDS-induced intestinal injury. MATERIALS AND METHODS: First, the chemical composition of NPS in SJZD and incomplete SJZD (iSJZD, including SJZD-R, SJZD-A, SJZD-P, SJZD-G) were comprehensively analyzed by UPLC-QTOF-MS, and comparing their chemical composition by multivariate statistical analysis to reveal the effect of a single herb on SJZD compatibility. Second, network pharmacology and molecular docking were used to uncover the micro-mechanisms of potential active compounds in SJZD for the treatment of SDS, and develop an active component combination (ACC) by accurate quantification. Subsequently, the action of the potential active compounds and ACC was verified through in vivo and in vitro. RESULTS: A total of 112, 77, 93, 87, and 67 compounds were detected in NPS of SJZD, SJZD-R, SJZD-A, SJZD-P, and SJZD-G, respectively. Changes in the chemical components of SJZD_NPS and iSJZD_NPS revealed that RG and RAM, as well as RAM and Poria significantly affected the dissolution of each other's chemical components, and the co-decoction of four herbs promoted the dissolution of the active compounds and inhibited toxic compounds. Furthermore, network pharmacology showed that 274 compounds of 15 categories in SJZD_NPS acted on the 186 key targets to treat SDS by inhibiting inflammation, enhancing immunity, and regulating gastrointestinal function and metabolism. Finally, through in vitro experiments, six compounds among 18 potential compounds were verified to markedly repair intestinal epithelium injury by modulating the FAK/PI3K/Akt or LCK/Ras/PI3K/Akt signaling pathway. It is worth mentioning that ACC, composed of 11 compounds accurately quantified, demonstrated significant in vivo treatment effects on intestinal damage with SDS similar to NPS or SJZD. CONCLUSIONS: This study elucidates the scientific evidence of the "Jun-Chen-Zuo-Shi" and "detoxification and synergistic" in the decocting process of SJZD. An ACC, the active component of SJZD, ameliorate SDS-induced intestinal injury by the FAK/PI3K/Akt signaling pathway, which provides a strategy for screening alternatives to effective combinations of TCMs.

Drug-polysaccharide/herb interactions and compatibility rationality of Sijunzi decoction based on comprehensive pharmacokinetic screening for multi-components in rats with spleen deficiency syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Sijunzi decoction (SJZD) is composed of four herbs, namely Ginseng Radix et Rhizoma (RG, Panax ginseng C.A.Mey.), Atractylodes Macrocephalae Rhizoma (AM, Atractylodes macrocephala Koidz.), Poria (Poria cocos (Schw.) Wolf), and Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle (GRP, derived from Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L.) based on the compatibility theory of traditional Chinese medicine (TCM), which is a classical formula for the treatment of spleen deficiency syndrome (SDS) in TCM. The polysaccharides and non-polysaccharides (NPSs) composition represented by flavonoids, saponins and terpenoids are the important pharmacodynamic material basis of SJZD. AIM OF THE STUDY: The aim of this study was to investigate the pharmacokinetic characteristics of SJZD in normal rats and SDS rats, and explore the potential interactions between NPSs and polysaccharides in SJZD, as well as the compatibility rationality of SJZD. MATERIALS AND METHODS: SDS model was established by oral administration of Radix Rhei (Rheum officinale Baill.) extract, loaded swimming, and intermittent fasting. A rapid, sensitive and reliable ultrafast liquid chromatography tandem mass spectrometry (UFLC-MS/MS) method was developed for the simultaneous analysis of fifteen representative compounds in rat plasma to investigate the differences in pharmacokinetics between normal and SDS rats. The SJZD-NPS samples were prepared by removing the polysaccharides of SJZD to explore the interactions between NPSs and polysaccharides of SJZD. According to the compatibility theory of TCM, four incomplete formulae of SJZD were obtained by randomly removing an herb (also called 'que fang' in TCM), and their pharmacokinetic differences were compared to elucidate the rationality of SJZD compatibility with oral administration to SDS rats. RESULTS: The established UFLC-MS/MS method showed perfect performance in simultaneously analyzing fifteen compounds of SJZD in rat plasma. Compared with normal rats, the absorption efficiency of NPSs in SDS rats was lower, accompanied by the prolonged residence time (Cmax and AUC0-t reduced, while MRT0-t increased). Polysaccharides have the potential to enhance intestinal metabolism of glycosides among these components, thereby contributing to the circulating distribution of corresponding metabolites (e.g. aglycones). Furthermore, the compatibility of the four herbs in SJZD could alter their pharmacokinetic characteristics, and potentially improve the absorption of the effective components of RG and AM, which is in accordance with the principle that "monarch" and "minister" herbs play a major role in TCM. In detail, the improved absorption of ginsenosides was mainly regulated by GRP (the "guide" herb in SJZD), together with the effects of AM ("minister" herb) and Poria ("adjuvant" herb) on the pharmacokinetics of components in GRP, implying that herb-herb interactions existed in SJZD and demonstrated the compatibility rationality of SJZD potentially. CONCLUSION: This study laid a solid foundation for revealing the pharmacodynamic material basis and subsequent action mechanism of SJZD, as well as provided new insights into the compatibility of SJZD. The comprehensive pharmacokinetic approach adopted in the current research also provides a valuable strategy for TCM formulae research.

Chinese dragon's blood ethyl acetate extract suppresses gastric cancer progression through induction of apoptosis and autophagy mediated by activation of MAPK and downregulation of the mTOR-Beclin1 signalling cascade.

Gastric cancer (GC) is a malignancy with high morbidity and mortality. Chinese dragon's blood is a traditional Chinese medicine derived from the red resin of Dracaena cochinchinensis (Lour.) S. C. Chen. However, the antigastric cancer effect of Chinese dragon's blood has not yet been reported. Herein, we demonstrated that Chinese dragon's blood ethyl acetate extract (CDBEE) suppressed the proliferative and metastatic potential of human gastric cancer MGC-803 and HGC-27 cells. CDBEE suppressed epithelial-mesenchymal transition in MGC-803 and HGC-27 cells. Moreover, CDBEE induced apoptotic and autophagic cell death in MGC-803 and HGC-27 cells. The cytotoxicity of CDBEE in human gastric epithelial GES-1 cells was dramatically weaker than that in human gastric cancer cells. Mechanistically, the activation of the mitogen-activated protein kinase (MAPK) signalling pathway was involved in the growth inhibition of MGC-803 and HGC-27 cells by CDBEE. Additionally, CDBEE-induced autophagic cell death was mediated by downregulation of the mammalian target of rapamycin (mTOR)-Beclin1 signalling cascade and upregulation of the ATG3/ATG7-LC3 signalling cascade. Importantly, CDBEE exhibited potent anti-GC efficacy in vivo without obvious toxicity or side effects. Therefore, CDBEE may be a promising candidate drug for the treatment of gastric cancer, especially for GC patients with aberrant MAPK signalling or mTOR signalling.

Citrate and hydroxycinnamate derivatives from Mume Fructus protect LPS-injured intestinal epithelial cells by regulating the FAK/PI3K/AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Mume Fructus (MF) is processed from the near-ripe fruit of Prunus mume (Siebold) Siebold & Zucc by drying at low temperature until the color turns black. MF is often used in Chinese medicine for the treatment of chronic diarrhea and dysentery. Previous studies have shown that the active components of MF against Crohn's disease (CD) are mainly citrate and hydroxycinnamate derivatives, which can alleviate the CD-induced inflammatory response and intestinal barrier damage. However, their molecular mechanisms on CD still need further elucidation. AIM OF THE STUDY: To investigate the protective effects and underlying mechanisms of citrate and hydroxycinnamate derivatives in MF on intestinal epithelial injury. MATERIALS AND METHODS: Network pharmacology technology was used to predict the anti-CD targets and molecular mechanisms of 4 citrate and 11 hydroxycinnamate derivative prototypes and 5 hydroxycinnamate derivative metabolites in the 40% ethanol fraction of MF (MFE40), the active anti-CD ingredient group of MF. Lipopolysaccharide (LPS)-treated IEC-6 cells were used to investigate the effects of the above components on the proliferation of damaged IEC-6 cells and to verify the molecular mechanism of their regulation on the FAK/PI3K/AKT signaling pathways for the promotion of the proliferation of IEC-6 cells. RESULTS: A "compound-target-pathway" network was constructed based on network pharmacology analysis, including 20 citrate and hydroxycinnamate derivatives that target 316 core proteins and 36 CD-related pathways, of which PI3K-AKT pathway and focal adhesion were the most enriched pathways. Further cell validation experiments showed that 1 citric acid (CA) compound and 10 hydroxycinnamate derivatives, including 3-O-caffeoylquinic acid (3CQA), 4-O-caffeoylquinic acid (4CQA), 5-O-caffeoylquinic acid (5CQA), caffeic acid (CFA), p-coumaric acid (PCMA), m-coumaric acid (MCMA), ferulic acid (FUA), isoferulic acid (IFUA), 3-hydroxyphenylpropionic acid (3HPPA) and hippuric acid (HPP), could promote the proliferation of IEC-6 cells and inhibit the damage of LPS to IEC-6 cells. Ethyl caffeate (ECFA), a hydroxycinnamic acid derivative, had no effect on promoting the proliferation of IEC-6 cells and was weak in inhibiting the damage of IEC-6 cells caused by LPS. Further mechanistic verification experiments showed that 7 citrate and hydroxycinnamate derivatives (CA, CFA, 3CQA, MCMA, FUA, 3HPPA, and HPP) could upregulate the expression of p-FAK, p-PI3K, and p-AKT proteins. Among them, CA had the better effect on activating the FAK-PI3K-AKT signaling pathway. CONCLUSIONS: Citrate and hydroxycinnamate derivatives in MF can ameliorate LPS-induced intestinal epithelial cell injury to demonstrate potential for Crohn's disease alleviation. This protective effect can be achieved by upregulating FAK/PI3K/AKT pathway.

Integrated analysis of phytochemical composition, pharmacokinetics, and network pharmacology to probe distinctions between the stems of Cistanche deserticola and C. tubulosa based on antidepressant activity.

Cistanches Herba (CH), as a nutritional and functional supplement used in food and health care products for centuries, consists of the stems of Cistanche deserticola and C. tubulosa. Our previous studies confirmed that the stems of C. tubulosa exerted advantageous antidepressant effect. However, whether the difference in the phytochemical compositions between the stems of C. deserticola and C. tubulosa would lead to diverse bioavailability and accompanying antidepressant effects remain unclear, as well as their specific bioactive compounds and underlying mechanism. In this study, a series of comparative studies showed that the antidepressant activity of C. tubulosa extract (CTE) was stronger than that of the C. deserticola extract (CDE), which was accompanied with the discovery of 10 differential markers from 52 identified compounds between CTE and CDE, and different pharmacokinetic behaviors of 9 prototype and 4 metabolites belonging to the glycosides between the CTE-treated and CDE-treated group in normal and depressive rats were simultaneously found by a validated UPLC-QTRAP-MS/MS method. Subsequently, network pharmacology prediction, in vitro and in vivo experiment verification from these differential markers further revealed that 7 compounds were confirmed to contribute to the antidepressant action of CH by inhibiting neuronal apoptosis mediated by mitochondrial function and activation of the AKT/GSK3ß signaling pathway, synchronously indicating most of those, with higher bioavailability in vivo after CTE administration, that were responsible for the stronger antidepressant effect of CTE over CDE. Hence, the integrated analysis of phytochemical composition, pharmacokinetics, and network pharmacology provide new insights into the applications of CH from different botanical origins against depression.

[Research progress on anti-tumor effect of Chinese dragon's blood].

As a traditional Chinese medicine, Chinese dragon's blood has multiple effects, such as activating blood to remove blood stasis, softening and dispelling stagnation, astringent and hemostasis, clearing swelling and relieving pain, regulating menstruation and rectifying the blood, so it is called "an effective medicine of promoting blood circulation". It has been widely used clinically to treat a variety of diseases. With the further research on Chinese dragon's blood, its anti-tumor medicinal value is gradually emerging. Modern pharmacological studies have shown that Chinese dragon's blood exerts anti-tumor effects mainly by inhibiting cell proliferation, inducing apoptosis, inducing DNA damage and cell cycle arrest, inducing senescence and autophagy of tumor cells, inhibiting metastasis and angiogenesis, as well as reversing multidrug resistance. This article focuses on the research progress on anti-tumor effects of Chinese dragon's blood extract and its chemical components, with a view to provide new references for the in-depth research and reasonable utilization of Chinese dragon's blood.

Coffee consumption and risk of prostate cancer: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review with meta-analysis of cohort studies to evaluate the association of coffee consumption with the risk of prostate cancer. DATA SOURCES: PubMed, Web of Science and Embase were searched for eligible studies up to September 2020. STUDY SELECTION: Cohort studies were included. DATA EXTRACTION AND SYNTHESIS: Two researchers independently reviewed the studies and extracted the data. Data synthesis was performed via systematic review and meta-analysis of eligible cohort studies. Meta-analysis was performed with the "metan" and "glst" commands in Stata 14.0. MAIN OUTCOMES AND MEASURES: Prostate cancer was the main outcome. It was classified as localised prostate cancer which included localised or non-aggressive cancers; advanced prostate cancer which included advanced or aggressive cancers; or fatal prostate cancer which included fatal/lethal cancers or prostate cancer-specific deaths. RESULTS: Sixteen prospective cohort studies were finally included, with 57 732 cases of prostate cancer and 1 081 586 total cohort members. Higher coffee consumption was significantly associated with a lower risk of prostate cancer. Compared with the lowest category of coffee consumption, the pooled relative risk (RR) was 0.91 (95% CI 0.84 to 0.98), I2= 53.2%) for the highest category of coffee consumption. There was a significant linear trend for the association (p=0.006 for linear trend), with a pooled RR of 0.988 (95% CI 0.981 to 0.995) for each increment of one cup of coffee per day. For localised, advanced and fatal prostate cancer, the pooled RRs were 0.93 (95% CI 0.87 to 0.99), 0.88 (95% CI 0.71 to 1.09) and 0.84 (95% CI 0.66 to 1.08), respectively. No evidence of publication bias was indicated in this meta-analysis. CONCLUSIONS: This study suggests that a higher intake of coffee may be associated with a lower risk of prostate cancer.

[Effect of Huaier aqueous extract on growth and metastasis of human non-small cell lung cancer NCI-H1299 cells and its underlying mechanisms].

This study aims to investigate the effect of Huaier aqueous extract on the growth and metastasis of human non-small cell lung cancer NCI-H1299 cells and its underlying mechanisms. MTT assay was used to detect the effect of Huaier aqueous extract on the proliferation of NCI-H1299 cells. Flow cytometry was used to examine the effect of Huaier aqueous extract on the apoptosis, cell cycle, and ROS level of NCI-H1299 cells. Wound healing assay was used to evaluate the effect of Huaier aqueous extract on the migration ability of NCI-H1299 cells. Western blot was used to detect the levels of proteins involving apoptosis, epithelial-mesenchymal transition(EMT), and MAPK signaling pathway in NCI-H1299 cells exposed to Huaier aqueous extract. The results showed that Huaier aqueous extract inhibited the proliferation of NCI-H1299 cells, and induced cell-cycle arrest at the phase S. Huaier aqueous extract promoted the apoptosis of NCI-H1299 cells by down-regulating the expression of anti-apoptotic protein Bcl-2. Moreover, Huaier aqueous extract increased ROS level and induced ferroptosis in NCI-H1299 cells. EMT played a critical role in cancer metastasis. Huaier aqueous extract reduced the migration ability of NCI-H1299 cells by inhibiting EMT of NCI-H1299 cells. In addition, this study revealed that Huaier aqueous extract inhibited MAPK signaling pathway in human non-small cell lung cancer NCI-H1299 cells, which may be one of Huaier's mechanisms in inhibiting growth and metastasis of NCI-H1299 cells. This study provides a new theoretical basis for the clinical treatment of lung cancer with Huaier, and important reference significance for further studies on the anti-tumor mechanisms of Huaier.

Chinese Dragon's Blood EtOAc Extract Inhibits Liver Cancer Growth Through Downregulation of Smad3.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies, which ranks the third leading cause of cancer-related death worldwide. The screening of anti-HCC drug with high efficiency and low toxicity from traditional Chinese medicine (TCM) has attracted more and more attention. As a TCM, Chinese dragon's blood has been used for the treatment of cardiovascular illness, gynecological illness, skin disorder, otorhinolaryngological illness, and diabetes mellitus complications for many years. However, the anti-tumor effect and underlying mechanisms of Chinese dragon's blood remain ill-defined. Herein we have revealed that Chinese dragon's blood EtOAc extract (CDBEE) obviously suppressed the growth of human hepatoma HepG2 and SK-HEP-1 cells. Moreover, CDBEE inhibited the migration and invasion of HepG2 and SK-HEP-1 cells. Additionally, CDBEE displayed good in vitro anti-angiogenic activity. Importantly, CDBEE treatment significantly blunted the oncogenic capability of HepG2 cells in nude mice. Mechanistically, CDBEE inhibited Smad3 expression in human hepatoma cells and tumor tissues from nude mice. Using RNA interference, we demonstrated that CDBEE exerted anti-hepatoma activity partially through down-regulation of Smad3, one of major members in TGF-ß/Smad signaling pathway. Therefore, CDBEE may be a promising candidate drug for HCC treatment, especially for liver cancer with aberrant TGF-ß/Smad signaling pathway.

Phenolic constituents, pharmacological activities, quality control, and metabolism of Dracaena species: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Dragon's blood (Chinese name: Xuejie), which comprises red resins obtained from several plants (27 species from 4 families), is drawing worldwide interests in medicinal applications owing to its broad pharmacological spectrum such as promoting blood circulation, regenerating muscle, relieving swelling and pain, maintaining hemostasis, etc. AIM OF THE STUDY: This work aims to evaluate current research progress on phenolic constituents, pharmacological activities, quality control, and metabolism of six Dracaena plants, namely, Dracaena cochinchinensis (Lour.) S.C.Chen, D. cambodiana Pierre ex Gagnep., D. cinnabari Balf. f., D. draco (L.) L., D. loureiroi Gagnep., and D. schizantha Baker, figure out the shortcomings of existing studies, and provide meaningful guidelines for future investigations. METHODS: Extensive database retrieval, such as SciFinder, PubMed, CNKI, ChemSpider, etc., was performed by using the keywords "Dracaena," "dragon's blood," as well as the Latin names of the six Dracaena species. In addition, relevant textbooks, patents, reviews, and documents were also employed to ensure sufficient information is collected. RESULTS: Flavonoids and their oligomers are the primary chemical clusters distributed in Dracaena plants. Pharmacological activities including analgesic, anti-inflammatory, antibacterial, hypolipidemic, hypoglycemic, and cytotoxic effects; bi-directional regulation effects on hemorheology; and cardiovascular and cerebrovascular effects have been disclosed by modern pharmacological evaluations. The chemical and metabolic profiles after oral administration of dragon's blood extract were preliminarily characterized. However, some of the pharmacological investigations reported only elementary methodologies and unreliable findings, and even worse, some important aspects were questionable or missing in these articles. CONCLUSIONS: Dragon's blood is a valuable source of bioactive compounds, mainly flavonoids and their oligomers. Its potential therapeutic effects on different diseases are attractive, such as the notable effect on cardiovascular diseases. In future studies, there is an urgent need to test the effect of this extract on appropriate cell lines and animal models to analyze its ethnopharmacological applications; moreover, "composition-effect correlation" methods and omics technologies are demanded for identifying the effective material basis and therapeutic mechanisms before entering into clinical trials. Moreover, attention should be paid to the chemical profiling and quality evaluation of this precious herbal medicine.

[Preparation, characterization and dissolution characteristics of dragon's blood extract nanosuspensions].

The single-factor test was used to optimize the high-pressure homogenization method to prepare the phenolic extract nanosuspensions(DBNs). The physicochemical properties of the obtained nanosuspensions were characterized and the cumulative release in vitro was evaluated. The results showed that the drug concentration was 0.5 g·L~(-1), the mass concentrations of PVPK30 and SDS were 0.5 and 0.25 g·L~(-1), respectively, the probe ultrasonic time was 5 min, the homogenization pressure was 900 bar, and the number of homogenization was 2 times. The prepared DBNs had an average particle size of(168.80±0.36) nm, polydispersity index(PDI) of 0.09±0.04, stability index(SI) of 0.85, and DBNs were stable for storage within 30 days. Scanning electron microscopy showed that the particle size of the dragon's blood extract was reduced and the uniformity was improved in the obtained nanosuspensions. X-ray diffraction pattern and differential scanning calorimetry showed that the phenolic extract of dragon's blood was still in an amorphous state after being prepared into nanosuspensions. The results of saturated solubility measurement showed that the solubility of DBNs lyophilized powder reached 6.25 g·L~(-1), while the solubility of DB raw powder was only 28.67 mg·L~(-1). The in vitro dissolution experiments showed that DBNs lyophilized powder accumulated in gastrointestinal fluid for 8 h. The release amount was 90%,the cumulative release of the raw powder in the gastrointestinal fluid for 24 h was less than 1%, and the solubility and dissolution rate of the DBNs lyophilized powder were significantly higher than the DB raw powder. The method is simple in process and convenient in operation, and can successfully prepare uniform and stable nanosuspensions to improve its solubility, and provides a research basis for solving the application limitation of dragon's blood extract.

[LC-MS guided isolation of two anti-inflammatory cyclic dihydrochalcane trimers from Chinese dragon's blood].

As an important integral part of traditional Chinese medicine chemical biology( TCMCB),it is of great importance to rapid isolate,and reliably identify the chemical components in herbal medicines. Phytochemical studies on the anti-inflammatory active part of Chinese dragon's blood,the red resin of Dracaena cochinchinensis,resulted in the isolation of two compounds,nordracophane( 1) and dracophane( 2),using LC-MS and chromatographic techniques( Silica gel,ODS and preparative HPLC). The structures,cyclic dihydrochalcane trimers,were elucidated on the basis of 1 D and 2 D NMR,MS,IR and UV spectral analysis. Compound 1 is a new compound,and 2 is isolated from D. cochinchinensis for the first time. Both compounds exhibited significant inhibition of nitric oxide production in lipopolysaccharides( LPS)-stimulated RAW264. 7 cells with IC50 values of( 14. 9±4. 50) and( 9. 0±0. 7) µmol·L-1.

[Anti-tumor activity of HIS-4,a biflavonoid from Resina draconis,on human hepatoma HepG2 and SK-HEP-1 cells].

The research of anti-hepatocellular carcinoma(HCC) drug has attracted more and more attention. Natural products are the important source of active compounds for cancer treatment. A biflavonoid HIS-4 was isolated from Resina draconis in our previous study. MTT assay, hoechst staining, and flow cytometry analysis were used to investigate the effects of HIS-4 on the proliferation and apoptosis of human hepatoma HepG2 and SK-HEP-1 cells. Moreover, the effects of HIS-4 on the migration and invasion ability of HepG2 and SK-HEP-1 cells were evaluated by wound healing assay and Transwell assay. In addition, MTT assay, flow cytometry analyses, Hoechst staining, wound healing assay, Transwell assay, and tube formation assay were used to explore the anti-angiogenic activity of HIS-4 in human umbilical vein endothelial cells(HUVECs). Mechanistically, the HIS-4 regulatory of signal pathways in H9 epG2 and SK-HEP-1 cells were analyzed by Western blot. This results showed that HIS-4 suppressed the proliferation of human hepatoma HepG2 and SK-HEP-1 cells. Moreover HIS-4 induced their apoptosis of HepG2 and SK-HEP-1 cells. HIS-4 inhibited the migration and invasion of HepG2 and SK-HEP-1 cells. Additionally, HIS-4 exhibited angiogenesis effects. Mechanistically, up-regulation of MAPK signaling pathway and down-regulation of mTOR signaling pathway may be responsible for anti-hepatoma activity of HIS-4. Therefore, HIS-4 may be a promising candidate drug for HCC treatment.

Rhamnolipid-involved antibiotics combinations improve the eradication of Helicobacter pylori biofilm in vitro: A comparison with conventional triple therapy.

Antibiotics resistance of H. pylori has been increasing constantly accompanied with decreasing clearance rate clinically, which is demonstrated to be closely related to biofilms with higher resistance than planktonic bacteria for the dense extracellular polymeric substances. Rhamnolipid (RHL) is proved to not only damage the structure of biofilm, but also potentially inhibit bacterial adhesion. To investigate if RHL could promote eradicating rate of the conventional triple therapy to H. pylori biofilm and hence attenuate the resistance and relapse of H. pylori, first-line antibiotics clarithromycin (CLR), amoxicillin (AMX) or/and proton pump inhibitor (PPI) involved single, dual or triple therapies were compared with RHL-containing drug combinations on eradicating H. pylori biofilm. The residual biofilm biomass, the survival of bacteria inside the remaining biofilm and the planktonic bacteria dispersed from the biofilm after treatment were tested. Combination with RHL significantly improved the ability of antibiotics to eradicate H. pylori biofilm, especially RHL combined with AMX and PPI could eradicate more than 95% of biofilm showing much more effective ability than the conventional triple therapy CLR + AMX + PPI. Additionally, the combination of RHL and antibiotics could effectively inhibit the biofilm formation at lower concentration. Thus, RHL might be used as a potential antibiotic adjuvant on anti-H. pylori therapy to enhance eradicating ability of antibiotics to biofilms.

[Identification of active components in Longxue Tongluo Capsules against ischemic brain injury based on component-activity relationship].

Ten fractions(A-J) were prepared by separation of Longxue Tongluo Capsules(LTC) by using silica gel column chromatography and orthogonal experimental design,showing similar chemical profiles with different abundances of peaks.These ten samples were assessed with UHPLC-QE OrbitrapHRMS for 97 common peaks.For the pharmacological activity experiment,three kinds of in vitro cell models including lipopolysaccharide(LPS)-induced BV-2 microglial cells NO release model,oxygen-glucose deprivation/reoxygenation(OGD/R)-treated HUVEC vascular endothelial cells injury model,and OGD/R-treated PC-12 nerve cells injury model were employed to evaluated the bioactivity of each fraction.Based on the contribution of each identified component,grey relation analysis and partial least squares(PLS) analysis were performed to establish component-activity relationship of LTC,identify the potential active components.After that,validation of the potential active components in LTC was carried out by using the same models.The results indicated that 4 phenolic compounds including 7,4'-dihydroxyhomoisoflavanone,loureirin C,4,4'-dihydroxy-2,6-dimethoxydihydrochalcone,and homoisosocotrin-4'-ol,might be the active components for anti-neuroinflammation effect;five phenolic compounds such as 3,5,7,4'-tetrahydroxyhomoisoflavanone,loureirin D,7,4'-dihydroxyhomoisoflavane,and 5,7-dihydroxy-4'-methoxy-8-methyflavane,might have positive effects on the vascular endothelial injury;three phenolic compounds including 5,7,4'-trihydroxyflavanone,7,4'-dihydroxy-5-methoxyhomoisoflavane,and loureirin D,might be the active components in LTC against neuronal injury.

LC-MS-guided isolation of anti-inflammatory 2-(2-phenylethyl)chromone dimers from Chinese agarwood (Aquilaria sinensis).

Fifteen previously undescribed 2-(2-phenylethyl)chromone dimers, along with two known analogues were isolated from Chinese agarwood (Aquilaria sinensis) by a LC-MS-guided fractionation procedure. Their structures were elucidated on the basis of spectroscopic and spectrometric data (1D and 2D NMR, IR, and HRESIMS). The isolated compounds exhibited significant inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with IC50 values in the range 0.6-37.1 µM.

High-Throughput Electrophysiology Screen Revealed Cardiotoxicity of Strychnine by Selectively Targeting hERG Channel.

Although the efficacy and the health care advantages of Chinese herbal medicine (CHM) have become increasingly recognized worldwide, the potential side effects and toxicity still restrict its broader application. This study established and applied an integrated platform anchored on automatic patch clamp system to screen and evaluate a collection of CHM extracts, compositions and monomeric compounds for in vitro cardiac toxicity. Of 1036 CHM samples screened, 2.79% significantly inhibited hERG channel activity. Among them, Strychnine was identified for the first time as a potent hERG inhibitor with an IC 50 of 6.65±1.04µ M in comparison to that of Dofetilide at 1.80±0.24µ M and Quinidine at 7.42±0.54µ M. Langendorff-perfusion experiments confirmed that strychnine increased QT interphase from 71.69±5.34 ms to 98.61±5.54 ms and decreased heart rates from 227.65±5.40 bmp to 162.91±14.70 bmp in isolated rat hearts. The cardiac toxicity effect of strychnine appears to be specific to hERG channel since an in vitro multiplex imaging analysis showed that it did not affect cellular phenotypes such as cell vitality, nucleus area, mitochondria mass and function, nor intracellular calcium in rat primary myocytes. This integrated high-throughput hERG patch clamp and high-content multi-parameter imaging cardiac toxicity screen approach should be useful for large-scale preclinical evaluation of complex Chinese herbal medicine.