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Two unique windmill-like aziridine-containing indole alkaloids, possessing an unprecedented 6/5/5/6/6/5/3 rigid ring system and an unusual azabicyclo[3.1.0]hexane core, were isolated from Alstonia scholaris. Their structures were established by spectroscopy, X-ray diffraction, and electronic circular dichroism calculations. The novel compounds exhibited significant anti-inflammatory bioactivity in vitro and alleviated LPS-induced acute lung injury in mice. [ABSTRACT FROM AUTHOR]

One novel naphthalene derivative, 2-octa-2′,4′,6′-atriynenaphthalene (1), together with eighteen known compounds (2–19) were isolated from the aerial parts of Dracocephalum moldavica L. Compounds 2, 8, 10, 13, 15–17 and 19 were obtained from the family Lamiaceae for the first time, and compounds 11 and 18 were firstly identified from the genus of Dracocephalum. All the isolates were evaluated for anti-complementary activities through the classical and alternative pathways, and the targets of the most active compounds on the complement activation cascade were also investigated. [ABSTRACT FROM AUTHOR]

Two new cassane-type derivatives (1–2), together with three known compounds (3–5), were isolated from the seed kernels of Caesalpinia sinensis. Their structures were elucidated on the basis of interpretation of comprehensive spectroscopic data, including HRESIMS and 1D/2D NMR spectroscopy, and the absolute configuration were established by means of ECD calculation. Compound 2, possessing a 16-degradative cassane skeleton, was rarely encountered in cassane diterpenoids isolated from the genus Caesalpinia. All compounds were evaluated for their anti-inflammatory activities against the overproduction of NO in LPS-stimulated RAW 264.7 macrophages, and compounds 1–5 could inhibit production of NO at the concentration of 50 μM. [ABSTRACT FROM AUTHOR]

1,8-Cineole (also known as eucalyptol) is mostly extracted from the essential oils of plants, which showed extensively pharmacological properties including anti-inflammatory and antioxidant mainly via the regulation on NF-κB and Nrf2, and was used for the treatment of respiratory diseases and cardiovascular, etc. Although various administration routes have been used in the application of 1.8-cineole, few formulations have been developed to improve its stability and bioavailability. This review retrospects the researches on the source, biological activities, mechanisms, and application of 1,8-cineole since 2000, which provides a view for the further studies on the application and formulations of 1,8-cineole. [ABSTRACT FROM AUTHOR]

The present study aims to investigate the roles of herb pairs containing Angelicae Sinensis Radix (Danggui) in Xin-Sheng-Hua Granule (XSHG) on hemolytic and aplastic anemia (HAA) mice. HAA model mice were induced by acetyl phenylhydrazine and cyclophosphamide; then the samples of XSHG and its decomposed recipes (DY, DC, DT, DH, DJ, and DZ) were orally administrated to these mice. Indicators of peripheral blood routine, organ index, and ATPase activities were tested. Moreover, the main effective components in these samples were also analyzed by UHPLC-TQ-MS/MS. Clear separation between the control and model groups from score plot of principal component analysis (PCA) was easily seen, indicating that HAA model was successfully conducted. Afterwards, relative distance calculation method between dose groups and control group from PCA score plot was adopted to evaluate the integrated effects of hematinic function of different samples. And the orders of hematinic effects were as follows: XHSG > DJ > DT > DZ > DH > DC > DY. Further analysis of these samples by UHPLC-TQ-MS/MS revealed that XSHG underwent complicated changes when herb pairs containing Danggui were excluded from XSHG, respectively. Compared with XSHG, the vast majority of active compounds in sample DY (formula minus herb pair Danggui-Yimucao) decreased significantly, which could partly explain why herb pair Danggui-Yimucao made great contribution to XSHG. These findings showed that withdrawal analysis method is a valuable tool to analyze the impacts of herb pairs containing Danggui on XSHG, which could lay foundation to reveal the compatibility rules of this formula. [ABSTRACT FROM AUTHOR]

Rhizoma Dioscoreae Collettii, is known as Huang Dioscorea collettii, Rhizoma Coptidis Brevisepalae or yellow ginger. It is neutral in nature and bitter in taste which is described to Gan (Liver) meridian, Wei (Stomach) meridian and Pangguang (Bladder) meridian. It was often used in the treatment of chyloid stranguria, gonorrhea, leucorrhagia, rheumatism arthralgia pain, joints disable, and lumbar knee pain syndrome in clinical. [ABSTRACT FROM AUTHOR]

Flacourtiaceae plants are widely used as folk medicines in traditional medicine systems for its chemical diversity and pharmacological activities. In many different areas, Flacourtiaceae plants are used as traditional medicines for the treatment of ulcers, malaria, rheumatism. The Flacourtiaceae plants contain a very plentiful chemical composition, and phytochemical studies show that the Flacourtiaceae plants contained terpenoids, aromatic glycosides, flavnoids, phenylpropanoids, alkaloids, fatty hydrocarbon, and other compounds. In pharmacological studies, various extract and isolated individual compounds exhibited antitumor, anti-oxidation, and anti-inflammatory activities. In this review, the literature data on the chemical constituents and pharmacological investigations of the Flacourtiaceae plants are summarized, to provide information about a more comprehensive chemical composition and detailed pharmacological activities of Flacourtiaceae plants, with a view of further development of clinical medication. However, research on quantitative analysis, toxicity, and drug safety in vitro and in vivo is still insufficient, and further research is required. [ABSTRACT FROM AUTHOR]

The rhizomes of the medicinal plant Hemsleya amabilis (Cucurbitaceae) yielded three new cucurbitane-type triterpene saponins xuedanosides K-M (1–3) by silica gel column, ODS column, and pre-HPLC techniques. The structure was determined by spectroscopic analysis and examined alongside existing data from prior studies. Compounds 1–3 were evaluated for cytotoxic activity against HeLa and HCT-8 human cancer cell lines and showed significant cytotoxicity with IC50 values of 2.01–14.56 and 8.94–27.48 μM, respectively. [ABSTRACT FROM AUTHOR]

Objective: To characterize the molecular mechanism underlying the antineoplastic activity of Celastrus orbiculatus Thunb. extracts (COE). Methods: The human hepatocellular carcinoma HepG2 cells with mammalian target of rapamycin (mTOR) knockdown expressed (HepG2/mTOR) were constructed using molecular biological technology. In vitro, the HepG2/mTOR− cells were treated with COE at various concentrations (10, 20, 40, 80, 160 and 320 µ g/mL). Cell viability was determined using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. According to the half-maximal inhibitory concentration (IC50) value (140 mg/L), the concentrations of COE in the subsequent experiment was set to alleviate cytotoxicity. The HepG2/mTOR− cells were divided into 5 groups: negative control (untreated), COE treatment groups (40, 80, 120 mg/L COE) and positive control group (cisplatin, DDP, 2 mg/L), respectively. Wild-type HepG2 cells were used as a blank control. The effects of COE on the cell apoptosis were analyzed by flow cytometry and transmission electronic microscopy (TEM), respectively. The protein expression levels of mTOR signal pathways were determined by Western blotting. In vivo, HepG2/mTOR− cells (2 × 106 cell/mice) were subcutaneously injected into the right flank of nude mice. Thirty-six female nude mice were randomly assigned to 6 groups according to body weight (6 mice per group) as follows: solvent vehicle control, Banmao Capsule treated group (BM, 195 mg/kg), Tegafur, Gimeracil and Oteracil Potassium Capsules (10 mg/kg) treated group, and different dosages of COE (10, 20, 40 mg/kg) groups. Tumor growth was monitored and immunohistochemical staining was used to examine the expression of apoptosis-related proteins in tumor tissues. Results: COE inhibited the proliferation significantly in a concentration-dependent manner in HepG2/mTOR− cells (P<0.01). COE significantly induced the apoptosis of HepG2/mTOR− cells (P<0.01), and the apoptotic bodies can be observed under TEM. COE significantly inhibits the proteins expression of mTOR-related signal pathways. In vivo, COE significantly inhibited tumor growth in nude mice (P<0.01). Moreover, the results showed that COE down-regulated the expression of Bcl-2 and Bcl-xL, and up-regulated the levels of Bax and caspase-3 protein (P<0.01). Conclusion: COE was a potential chemotherapeutic drug in HCC treatments via targeting mTOR signal pathway. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of Celastrus Orbiculatus extracts (COE) on metastasis in hypoxia-induced hepatocellular carcinoma cells (HepG2) and to explore the underlying molecular mechanisms. Methods: The effect of COE (160, 200 and 240 µ g/mL) on cell viability, scratch-wound, invasion and migration were studied by 3-4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide (MTT), scratch-wound and transwell assays, respectively. CoCl2 was used to establish a hypoxia model in vitro. Effects of COE on the expressions of E-cadherin, vimentin and N-cadherin were investigated with Western blot and immunofluorescence analysis, respectively. Results: COE inhibited proliferation and metastasis of hypoxia-induced hepatocellular carcinoma cells in a dose-dependent manner (P<0.01). Furthermore, the expression of epithelial-mesenchymal transition (EMT) related markers were also remarkably suppressed in a dose-dependent manner (P<0.01). In addition, the upstream signaling pathways, including the hypoxia-inducible factor 1 α (Hif-1 α) and Twist1 were suppressed by COE. Additionally, the Hif-1 α inhibitor 3-5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1), potently suppressed cell invasion and migration as well as expression of EMT in hypoxia-induced HepG2 cells. Similarly, the combined treatment with COE and YC-1 showed a synergistic effect (P<0.01) compared with the treatment with COE or YC-1 alone in hypoxia-induced HepG2 cells. Conclusions: COE significantly inhibited the tumor metastasis and EMT by suppressing Hif-1 α/Twist1 signaling pathway in hypoxia-induced HepG2 cell. Thus, COE might have potential effect to inhibit the progression of HepG2 in the context of tumor hypoxia. [ABSTRACT FROM AUTHOR]

Three new Lycopodium alkaloids (1–3), together with 15 known alkaloids, were isolated from club moss Lycopodium japonicum. Their structures were determined by extensive spectroscopic analysis, including 1D and 2D NMR spectra. Compound 1 has an unusual β-oriented methyl group substituted at C-15 and an α-hydroxy cyclopentenone moiety. All new alkaloids were evaluated for the inhibition of T-type calcium channel. [ABSTRACT FROM AUTHOR]

Background: Celastrus orbiculatus (Celastraceae) are used as traditional Chinese medicine to treat inflammation and cancer. This study aims to evaluate the effect of Celastrus orbiculatus extract (COE) on the apoptosis in human hepatic carcinoma HepG2 cells with mTOR overexpression. Methods: The stable expression of mTOR in HepG2 cells (HepG2/mTOR+) were established by lipofectin transfection of GV238-mTOR recombinant plasmids and further antibiotic selection. Human hepatic carcinoma HepG2/mTOR+ cells were treated with different concentrations (20, 40, 80, 160, and 320 μg/mL) of COE for 24 h. The cell proliferation upon COE treatment was detected by MTT. Apoptosis was measured by Flow Cytometry. The activity of mTOR signaling pathway was detected by Western Blotting. Results: COE significantly inhibited the proliferation of HepG2/mTOR+ cells. The expression levels of Bax and Caspase-3 protein were increased in the HepG2/mTOR+ cells in a dose-dependent manner. The proteins expression of Bcl2, Bcl-2 L12, mTOR, phospho-mTOR, 4EBP1, phospho-4EBP1, P70S6k, and phospho-P70S6k in HepG2/mTOR+ cells were reduced in dose-dependent manners. Furthermore, COE and mTOR inhibitor rapamycin (RAPA) synergistically induced apoptosis in HepG2/mTOR+ cells by regulating apoptosis-related proteins and inhibiting mTOR signaling pathways. Conclusion: COE could inhibit the proliferation of HepG2/mTOR+ cells, and induce the cell apoptosis. The mechanisms may be related to the regulation of the expression of Bcl-2, Bcl-2 L12, and mTOR signaling pathways. These data suggest that COE may be a potential treatment for human hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

The compatibility between Danggui (Angelicae Sinensis Radix) and Honghua (Carthami Flos) is a known herb pair, which could activate blood circulation and dissipate blood stasis effects. In this paper, we quantified seven main bio-active components (hydroxysafflor yellow A, caffeic acid, p-coumaric acid, kaempferol-3-O-rutinoside, ferulic acid, 3-n-butylphthalide, and ligustilide) in plasma samples in vivo by UPLC-TQ/MS method and investigatedwhether the pharmacokinetic (PK) behaviors of the seven components could be altered in blood stasis rats after oral administration of the Gui-Hong extracts. It was found that the Cmax and AUC0-t of these components in blood stasis rats had increasing tendency compared with normal rats. Most components in model and normal rats had significant difference in some pharmacokinetic parameters, which indicated that the metabolism enzymes and transporters involved in the metabolism and disposition of these bio-active componentsmay bealtered in blood stasis rats. This study was the first report about the pharmacokinetic investigation between normal and blood stasis rats after oral administrationof Gui-Hong extracts, and these results are important and valuable for better clinical applications of Gui-Hong herb pair and relatedTCM formulae. [ABSTRACT FROM AUTHOR]

Objective. To investigate the absorption property of the representative hydrolyzable tannin, namely corilagin, and its hydrolysates gallic acid (GA) and ellagic acid (EA) from the Fructus Phyllanthi tannin fraction (PTF) in vitro. Methods. Caco-2 cells monolayer model was established. Influences of PTF on Caco-2 cells viability were detected with MTT assay. The transport across monolayers was examined for different time points, concentrations, and secretory directions. The inhibitors of P-glycoprotein (P-gp), multidrug resistance proteins (MRPs), organic anion transporting polypeptide (OATP) and sodium/glucose cotransporter 1 (SGLT1), and tight junction modulators were used to study the transport mechanism. LC-MS method was employed to quantify the absorption concentration. Results. The apparent permeability coefficient (Papp) values of the three compounds were below 1.0 × 10−6 cm/s. The absorption of corilagin and GA were much lower than their efflux, and the uptake of both compounds was increased in the presence of inhibitors of P-gp and MRPs. The absorption of EA was decreased in the company of OATP and SGLT1 inhibitors. Moreover, the transport of corilagin, GA, and EA was enhanced by tight junction modulators. Conclusion. These observations indicated that the three compounds in PTF were transported via passive diffusion combined with protein mediated transport. P-gp and MRPs might get involved in the transport of corilagin and GA. The absorption of EA could be attributed to OATP and SGLT1 protein. [ABSTRACT FROM AUTHOR]

The plants of the genus Phyllanthus (Euphorbiaceae) have been used as traditional medicinal materials for a long time in China, India, Brazil, and the Southeast Asian countries. They can be used for the treatment of digestive disease, jaundice, and renal calculus. This review discusses the ethnopharmacological, phytochemical, and pharmacological studies of Phyllanthus over the past few decades. More than 510 compounds have been isolated, the majority of which are lignins, triterpenoids, flavonoids, and tannins. The researches of their remarkable antiviral, antioxidant, antidiabetic, and anticancer activities have become hot topics. More pharmacological screenings and phytochemical investigations are required to support the traditional uses and develop leading compounds. [ABSTRACT FROM AUTHOR]

5,7-dihydroxy-3',4',6-trimethoxyflavone, commonly known as eupatilin, is a traditional Asian medicinal plant, which is mainly used for the treatment of gastritis, as well as its use as an anti-inflammatory agent. Eupatilin is a bioactive compound; however, its effects on osteosarcoma (OS) have remained to be elucidated. Therefore, the present study aimed to investigate the effects of eupatilin on this malignant bone tumor, using the U-2 OS cell line. The experimental results revealed t hat eupatilin i nhibited U -2 OS cell growth in a concentration-dependent manner and induced G2/M phase cell cycle arrest and apoptosis. Additionally, western blot analysis indicated that eupatilin was able to trigger the mitochondrial apoptotic pathway, demonstrated by the enhanced Bax/B cell lymphoma-2 ratio, decrease in mitochondrial membrane potential, release of cytochrome c, caspase-3 and -9 activation and poly(ADP-ribose)polymerase cleavage detected in the U-2 OS cells. These results indicated that eupatilin was able to inhibit U-2 OS cancer cell proliferation by the induction of apoptosis via the mitochondrial intrinsic pathway. Eupatilin may therefore represent a novel anticancer drug for use in the treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Houttuynia cordata (HC) has been used as a folk therapy to treat pulmonary infections. This study aimed to determine the role and mechanism of action of polysaccharides isolated from HC (HCP) in lipopolysaccharide (LPS)-induced ALI in the mice. Materials and methods LPS was delivered by the intratracheal route to Balb/c mice 2 h before HCP (40, 80 and 160 mg/kg) administration. Results The number of total cells, protein and tumor necrosis factor-α (TNF-α) concentrations in bronchoalveolar lavage fluid, the wet/dry weight ratio (w/d) of lungs and pulmonary pathology of each mouse were analyzed, it was found that HCP significantly alleviated ALI induced by LPS. Moreover, in lungs of mice, it was found that the infiltration of inflammatory cells, the expression of Toll-like receptor 4 and complement deposition were significantly decreased by HCP treatment. In vitro assays showed that C5a, a complement activation product, induced significant macrophage migration and treatment with HCP prevented it. The in vitro results also proved that LPS increased nitric oxide and pro-inflammatory cytokines (TNF-α, interleukin-6, and interleukin-1β) production, and HCP antagonized these effects of LPS. It was also found that HCP alone augmented secretion of some pro-inflammatory cytokines. Conclusion These results indicate that HCP may alleviate LPS induced lung inflammatory injury, which may be associated with its inhibitory effect on the over activation of complement and macrophages. This suggests a potential role to treat ALI. [ABSTRACT FROM AUTHOR]

Background What was the relationship of Fuzheng Huayu recipe (FZHY) inhibiting hepatocyte apoptosis and HSC activation at different stage of liver fibrosis? In order to answer this question, the study was carried out to dynamically observe FZHY's effect on hepatocyte apoptosis and HSC activation and further explored underling mechanism of FZHY against hepatocyte apoptosis. Methods Mice were randomly divided into four groups: normal, model, FZHY, and N-acetylcystein (NAC) groups. Acute hepatic injury and liver fibrosis in mice were induced by CCl4. Three days before the first CCl4 injection, treatment with FZHY powder or NAC respectively was started. In vitro, primary hepatocytes were pretreated with FZHY medicated serum or ZVAD- FMK and then incubated with ActD and TNF-α. Primary HSCs were treated with DNA from apoptotic hepatocytes incubated by Act D/TNF-α or FZHYmedicated serum. Liver sections were analyzed for HE staining and immunohistochemical evaluation of apoptosis. Serum ALT and AST levels and Alb content and TNF-α expression in liver tissue were detected. Hyp content was assayed and collagen deposition was visualized. Expressions of α-SMA and type I collagen were analyzed by immunofluorescence and immunoblotting. Flow cytometry, immunofluorescence, and DNA ladder for hepatocyte apoptosis and immunoblotting for TNF-R1, Bcl-2 and Bax were also analyzed. Results Mice showed characteristic features of massive hepatocytes apoptosis in early stage of liver injury and developed severe hepatic fibrosis in later phase. FZHY treatment significantly alleviated acute liver injury and hepatocyte apoptosis, and inhibited liver fibrosis by decreasing α-SMA expression and hepatic Hyp content. In vitro, primary hepatocytes were induced by TNF-α and Act D. The anti-apoptotic effect of FZHY was generated by reducing TNFR1 expression and balancing the expressions of Bcl-2 and Bax. Meanwhile, the nuclear DNA from apoptotic hepatocytes stimulated HSC activation in a dose dependent manner, and the DNA from apoptotic hepatocytes treated with FZHY or Z-VAD-FMK reduced HSC activation and type I collagen expression. Conclusion These findings suggested that FZHY suppressed hepatocyte apoptosis through regulating mediators in death receptor and mitochondrial pathways, and the effect of FZHY on hepatocyte apoptosis might play an important role in inhibiting liver fibrosis. [ABSTRACT FROM AUTHOR]

As a traditional folk medicine, Acorus tatarinowii Schott was used to treat digestive diseases, such as diarrhea, which may be related to Candida albicans infection; however according to literature surveys, there have been few studies of A. tatarinowii focusing on its antimicrobial activity, and almost all describe investigations using crude extracts or fractions. The aims of the current study were to isolate and identify antifungal fractions of A. tatarinowii based on their antifungal activity, explore the preliminary mechanism of 60% ethanol elution (AT60) by metabonomics, and evaluate the antifungal activity of AT60 in vivo and in vitro , to provide natural resources against fungal infections. As a pilot evaluation of activity, A. tatarinowii fractions and compounds with antifungal bioactivity were isolated by bioactive-guided column chromatography, and identified by LC-QTOF-MS/MS and NMR spectroscopy. The antifungal effects of the active ingredients against resistant C. albicans were evaluated by in vivo and in vitro colony forming unit assays. The mechanism underlying the activity of AT60 against C. albicans was explored using an LC-QTOF-based metabonomics approach and fluorescence microscopy imaging. AT60 showed better activity against C. albicans than the same dose of the first line antifungal drugs, fluconazole and itraconazole (positive control drugs). Subsequent phytochemical investigation of AT60 identified twenty-five known compounds, six of which were isolated: asaraldehyde (7), 1-(2,4,5-trimethoxyphenyl)-1,2-propanediol (12), α-asarone (14), β-asarone (15), γ-asarone (18), acotatarone C (19). Further, the compounds α-asarone (14) and acotatarone C (19) may be responsible for the antifungal activity, and exhibit synergistic effects. Metabonomics analysis indicated that AT60 can inhibit biofilm formation by regulating the C. albicans protein kinase C pathway. Our results show that A. tatarinowii has potent bioactivity against C. albicans in vitro and in vivo, and can be considered an antifungal botanic agent. Image 1 [ABSTRACT FROM AUTHOR]

As a folk medicine, Phlomis likiangensis is traditionally used in China to activate collaterals and protect cardiovascular system. We hypothesized that the beneficial effects of Phlomis likiangensis may be related to vasodilatation. In the present study, twelve known iridoid glucosides (1−12) were isolated from Phlomis likiangensis. The vasodilatory effects and the underlying mechanisms of the main components (iridoid glucosides) of Phlomis likiangensis on rat aortic rings were investigated. The result showed that iridoid glucosides significantly increased the vasodilatation in rat aortic rings, which was abolished by removing the endothelium of the vessels or by eliminating the generation of nitric oxide. Finally, the structure-activity relationship of compounds 1–12 was also speculated. Our findings provide the first evidence that the iridoid glucosides of Phlomis likiangensis may be the pharmacodynamic basis for its traditional efficacy. Unlabelled Image [ABSTRACT FROM AUTHOR]

Dendranthema morifolium cv. 'jinsidaju', cultivated only in Kaifeng, has been eaten for more than 1000 years. During the antioxidant-activity-guided studies on its chemistry and health care function, two new bisabolane-type sesquiterpenes, (6 R ,7 R)-7-hydroxybisabol-2,9 E ,11-triene-4-one (jinsidajuol A, 1) and (6 R ,7 R)-7-hydroxy-11-methoxybisabol-2,9 E -diene-4-one (jinsidajuol B, 2), and thirteen known compounds (3 – 15) were isolated from the flowers. Their structures were elucidated by 1D and 2D NMR spectroscopy and HRMS. 1 and 2 are the first example of bisabolane-type sesquiterpenes isolated from the genus Dendranthema. Compounds 6 – 8 , 12 and 13 exhibited strong scavenging activities on the ABTS radical cation with IC 50 3.33, 5.67, 2.00, 2.50, 5.33 μg/mL, respectively. The IC 50 values of all compounds on HepG2 human hepatoma tumor cell line were higher than 50 μM. Unlabelled Image [ABSTRACT FROM AUTHOR]

Background Triple-negative breast cancer (TNBC) is an aggressive and deadly breast cancer subtype with limited treatment options. It is necessary to seek complementary strategies for TNBC management. Taraxacum mongolicum , commonly named as dandelion, is a herb medicine with anti-cancer activity and has been utilized to treat mammary abscess, hyperplasia of mammary glands from ancient time in China, but the scientific evidence and action mechanisms still need to be studied. Aim of the study This study was intended to investigate the therapeutic effect and molecular mechanisms of dandelion extract in TNBC cell line. Methodology Dandelion extract was prepared and purified, and then its chemical composition was determined. Cell viability was evaluated by MTT assay. Analysis of cell apoptosis and cell cycle was assessed by flow cytometry. The expression levels of mRNA and proteins were determined by real-time PCR and Western blotting, respectively. Caspase inhibitor Z-VAD-FMK and CHOP siRNA were used to confirm the cell apoptosis induced by dandelion extract. Results Dandelion extract significantly decreased MDA-MB-231cell viability, triggered G2/M phase arrest and cell apoptosis. Concurrently, it caused a markedly increase of cleaved caspase-3 and PARP proteins. Caspase inhibitor Z-VAD-FMK abolished the apoptosis triggered by dandelion extract. The three ER stress-related signals were strongly induced after dandelion treatment, including increased mRNA expressions of ATF4, ATF6, XBP1s, GRP78 and CHOP genes, elevated protein levels of phosphorylated PERK, eIF-2α, IRE1, as well as the downstream molecules of CHOP and GRP78. MDA-MB-231 cells transfected with CHOP siRNA significantly reduced apoptosis induced by dandelion extract. The underlying mechanisms at least partially ascribe to the strong activation of PERK/p-eIF2α/ATF4/CHOP axis. Conclusion ER stress related cell apoptosis accounted for the anti-cancer effect of dandelion extract, and these findings support dandelion extract might be a potential therapeutic approach to treat TNBC. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Acute alcohol intoxication (AAI) is a frequent emergency, but therapeutic drugs with superior efficacy and safety are lacking. Panax ginseng (PG) and Hippophae rhamnoides (HR) respectively has a wide application as a complementary therapeutic agent in China for the treatment of AAI and liver injury induced by alcohol. We investigated the effects of aqueous extracts from PG and HR (AEPH) on AAI mice and identified its underlying mechanisms. Materials and methods Models of AAI were induced by intragastric administration of ethanol (8 g/kg). Seventy-two Specific pathogen-free (SPF) male Kunming mice were randomly divided into six groups: normal group, positive control group, AEPH of low dosage (100 mg/kg) group, AEPH of medium dose (200 mg/kg) group, AEPH of high dosage (400 mg/kg) group and model group. The mice were treated with metadoxine (MTD, 500 mg/kg) and AEPH. Thirty minutes later, the normal group was given normal saline, while the other groups were given ethanol (i.g., 8 g/kg). The impact of AEPH was observed. In the same way, another seventy-two Kunming mice were randomly divided into six groups equally. The blood ethanol concentration at 0.5, 1, 1.5, 2, 3 and 6 h after ethanol intake was determined by way of gas chromatography. The activity of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and microsomal ethanol oxidase (EO) in liver, and the concentration of β-endorphin (β-EP), leucine-enkephalin (LENK) in the brain were determined by enzyme-linked-immunosorbent serologic assay (ELISA). Results AEPH markedly prolonged alcohol tolerance time and shortened sober-up time after acute ethanol administration. AEPH decreased blood ethanol levels in six tests after ethanol intake. The 7-day survival rate of AEPH group was obviously superior to model group. AEPH increased the activities of ADH, ALDH, and decreased EO activity in liver. The crucial find was that AEPH markedly decreased β -EP and LENK concentration in the brain. Conclusions AEPH can markedly increase the levels of ADH, ALDH, decrease EO activity in liver and decrease the concentration of β-EP and LENK in the brain to against acute alcohol intoxication in mice. [ABSTRACT FROM AUTHOR]

Saposhnikoviae Radix (SR) is a traditional Chinese medicine, known as "Fangfeng". As one of the main active components, Saposhnikoviae Radix polysaccharides (SP) demonstrated a range of biological activities, especially immunity regulation activity. This study aimed at exploring whether polysaccharides have activity after degradation, then discovering the potential effective fragments of SP. Here we establish the chromatographic fingerprints method for 32 batches of 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatives of oligosaccharides by HPLC, meanwhile evaluating its immunomodulatory activity in vivo. Then, the potential effective fragments of SP were screened out based on the spectrum-effect relationship analysis between fingerprints and the pharmacological results. Besides, liquid chromatography ion trap-time of flight mass spectrometry (LC-IT-TOF MS) coupled with multiple data-mining techniques was used to identify the potential effective oligosaccharides. These findings showed that the hydrolysate of SP have significant immunomodulatory, and the immunity regulation activity varies under different hydrolysis conditions. The 4 potential effective peaks of the hydrolysate of SP were mined by spectrum-effect relationship. Finally, the chemical structure of 4 potential effective oligosaccharide fragments of SP was elucidated based on LC-IT-TOF MS. F10 was inferred tentatively to be Hex1→6Hex1→6Hex1→6Hex1→6Hex1→6Gal; F18 was confirmed to be Rhamnose; F14 was inferred tentatively to be Hex1→4Hex1→ 4Hex1→4Gal and F25 was tentatively inferred to be Ara1→6Gal. This study may provide a sound experimental foundation in the exploration of the active fragments from macromolecular components with relatively complex structures such as polysaccharides. [Display omitted] • An integrated strategy for the discovery of the active fragments of polysaccharides. • Developed a general workflow for the characterization of oligosaccharides. • Evaluated the immunomodulatory effect of polysaccharides after degradation. [ABSTRACT FROM AUTHOR]

The combination of Astragulus embranaceus (Fisch.) Bge (Huangqi) and Dioscorea opposita Thunb (Shanyao) are one of the most widely accepted herb pairs in traditional Chinese medicine prescriptions for treating sarcopenia. However, the mechanisms underlying the combination of these herbs for anti-sarcopenia treatment are not yet fully understood. To investigate the potential effect of the Astragulus embranaceus (Fisch.) Bge and Dioscorea opposita Thunb herb pair (Ast-Dio) on sarcopenia in mice that have been induced with senile type 2 diabetes mellitus, as well as to explore the underlying mechanisms related to the Rab5a/mTOR signaling pathway and mitochondrial quality control. Network pharmacology was utilized to identify the main active ingredients of Ast-Dio and potential therapeutic targets for sarcopenia. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted to explore the underlying mechanisms of Ast-Dio in treating sarcopenia. The high-performance liquid chromatography method coupled with triple-quadrupole tandem mass spectrometry was developed to quantify the major constituents of Ast-Dio. Male C57/BL6 mice, aged 12 months, induced with type 2 diabetes mellitus via streptozotocin were divided into three groups for 8 weeks: the model group, Ast-Dio treatment group (7.8 g/kg), and metformin treatment group (100 mg/kg). Normal control groups included mice aged 3 and 12 months, respectively. The study monitored changes in fasting blood glucose levels, grip strength, and body weight during 8 weeks of intragastric administration. Liver and kidney function in mice was evaluated by measuring the levels of serum creatinine, alanine transaminase, and aspartate transaminase. Skeletal muscle mass condition was evaluated by muscle weight, and hematoxylin and eosin staining. Protein and mRNA expressions related to muscle atrophy, mitochondrial quality control, and the Rab5a/mTOR signaling pathway were detected using immunofluorescence staining, immunohistochemical staining, Western blotting, and quantitative real-time polymerase chain reaction. In addition, transmission electron microscopy was employed to investigate the condition of mitochondria in the groups. Through the prediction analysis of network pharmacology, we identified mTOR as one of the primary targets for Ast-Dio therapy of sarcopenia. Gene Ontology functional enrichment analysis revealed that mitochondrial control quality is crucial in the treatment of sarcopenia with Ast-Dio. Our findings showed that senile type 2 diabetes mellitus induced muscle mass loss and a reduction in grip strength, both of which were dramatically restored by Ast-Dio treatment. Notably, Ast-Dio increased Myogenin expression while decreasing Atrogin-1 and MuRF-1 expression. Additionally, Ast-Dio activated Rab5a/mTOR and its downstream effector AMPK. Moreover, Ast-Dio modulated mitochondrial quality control by decreasing Mitofusin-2 expression while increasing the expression of TFAM, PGC-1α, and MFF. Our results suggest that Ast-Dio treatment may alleviate sarcopenia in mice with senile type 2 diabetes mellitus through its effects on the Rab5a/mTOR pathway and mitochondrial quality control. [Display omitted] • Sarcopenia is a generalized skeletal muscle disorder that can be induced by a senile type 2 diabetes mellitus. • Ast-Dio relieve sarcopenia by the downregulation of mitochondrial fusion, and upregulation of fission and biogenesis. • The Rab5a/mTOR signaling pathway plays a significant role in the treatment of sarcopenia with the Ast-Dio. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance : Sennoside A is a natural anthraquinone component mainly derived from rhubarb and has been routinely used as a clinical stimulant laxative. However, long-term application of sennoside A may lead to drug resistance and even adverse reactions, thus limiting its clinical use. Therefore, to reveal the time-dependent laxative effect and potential mechanism of sennoside A is of critical importance. Aim of the study : This study was conducted to investigate the time-dependent laxative effect of sennoside A and unveil its underlying mechanism from the perspective of gut microbiota and aquaporins (AQPs). Materials and methods : Based on a mouse constipation model, 2.6 mg/kg sennoside A was administered orally for 1, 3, 7, 14 and 21 days, respectively. The laxative effect was assessed by the fecal index and fecal water content, the histopathology of the small intestine and colon was evaluated by hematoxylin-eosin staining. Gut microbiota changes was observed by 16S rDNA sequencing, and colonic AQPs expression was analyzed by quantitative real-time polymerase chain reaction and western blotting. Partial least-squares regression (PLSR) was used to screen out the effective indicators contributing to the laxative effect of sennoside A. The effective indicators were then fitted to time by a drug-time curve model to analyze the trend of efficacy of sennoside A, and the optimal time of administration was derived by comprehensive analysis with a three-dimensional (3D) time-effect image. Results : Sennoside A had a significant laxative effect at 7 days of administration with no pathological changes in the small intestine or colon; however, at 14 or 21 days of administration, the laxative effect diminished and slight damage to the colon was observed. Sennoside A affects the structure and function of gut microbes. The alpha diversity showed that the abundance and diversity of gut microorganisms reached the highest value after 7 days of administration. Partial least squares discriminant analysis showed that the composition of the flora was close to normal when administered for less than 7 days, but was closest to the composition of constipation over 7 days. The expression of aquaporin 3 (AQP3) and aquaporin 7 (AQP7) decreased gradually after the administration of sennoside A, with the lowest expression at 7 days, and then increased gradually afterwards, while the expression of aquaporin 1 (AQP1) was the opposite. The PLSR results showed that AQP1, AQP3, Lactobacillus , Romboutsia , Akkermansia and UCG_005 contributed more to the laxative effect of the fecal index, and after fitting with the drug-time curve model, each index showed a trend of increasing and then decreasing. The comprehensive evaluation of the 3D time-effect image concluded that the laxative effect of sennoside A reached its best after 7 days of administration. Conclusion : Sennoside A should be used in regular dosages for less than one week, as it provides significant relief of constipation and exhibits no colonic damage within 7 days of administration. In addition, Sennoside A exerts its laxative effect by regulating gut microbiota of Lactobacillus Romboutsia , Akkermansia and UCG_005 and water channels of AQP1 and AQP3. [Display omitted] • For constipation relief, Sennoside A should be used at regular dose for less than 7 days. • Sennoside A exerts the laxative effect by regulating gut microbiota and aquaporins. • The optimal time is obtained through a comprehensive analysis of fecal index, intestinal histopathology, gut microbiota and aquaporins. [ABSTRACT FROM AUTHOR]

A phytochemical investigation of the whole plants of T. delavayi led to the isolation of five new dimeric benzylisoquinoline alkaloids, thalidelavines A–E (1 – 5), together with six known congeners (6 – 11). The structures and absolute configurations of new compounds were established based on analyses of spectroscopic data, ECD calculations, and single crystal X-ray crystallography. Thalidelavines A–E (1 – 5) were structurally complex bisbenzylisoquinoline alkaloids with various configurations. These isolated alkaloids were evaluated for their cytotoxic and immunosuppressive effects. Among them, both 9 and 10 displayed significant cytotoxicities against T98G cell lines with an IC 50 value of 2.1 μM, compared with the positive CPT-11 (IC 50 = 3.0 μM). In addition, 5 – 7 showed remarkable immunosuppressive effects. These findings not only enrich the structural diversity of bisbenzylisoquinoline alkaloids, but also provide potential candidates for the further development of the antitumor and immunosuppressive agents. [Display omitted] [ABSTRACT FROM AUTHOR]

The flower of Edgeworthia gardneri is consumed in beverages in Tibet and has potential health benefits for diabetes. As a part of our continuous studies on dietary supplements for diabetes, two monomers, five dimers and one trimer of coumarins were isolated from the flowers of E. gardneri . One dimer was a new compound ( 1 ) and its structure was determined by spectroscopic methods, including multiple NMR techniques and mass spectrometry. The inhibitory activities of all coumarins against α-amylase and α-glucosidase were evaluated. Compound 4 displayed potent inhibitory effect on both α-amylase and α-glucosidase, with an IC 50 of 90 and 86 μg/mL, respectively. The IC 50 of compound 3 against α-glucosidase was 18.7 μg/mL, and its inhibition mode was noncompetitive. Based on the fluorescence analysis, the binding constant and the number of binding sites of compound 3 were calculated as 2.05 × 10 5 and 1.24, respectively. Furthermore, the interaction between compound 3 and α-glucosidase was a spontaneous process that was driven mainly by hydrophobic force. This study could facilitate the utilization of E gardneri as functional food ingredient. [ABSTRACT FROM AUTHOR]

The root bark of Morus alba Linn. (M. alba), a traditional folk medicine, has been documented in the Chinese Pharmacopoeia, which has been widely used for asthma, fever, pneumonia, edema, vomit, colitis, bronchitis and keratitis diseases. Some of the diseases may be related to respiratory, digestive, urinary tract infections. Although Diels-Alder adducts (DAAs), flavonoids, 2-arylbenzofurans and stilbene compounds have been isolated from the root bark of M. alba , few compounds are reported for their antimicrobial efficacy in viv o and the mechanism. The aim of the study was to isolate and identify compounds of the root bark of M. alba in view of their anti-MRSA bioactivity, evaluate the anti-MRSA bioactivity of compounds and 60% ethanol elution (MA-6) in vitro and in vivo , and explore preliminary antibacterial mechanism in order to provide natural resources against MRSA infection. Systematic phytochemical investigations were carried out according to the thin layer chromatography (TLC) of the active fraction MA-6 to find more anti-MRSA ingredients. The compounds of the root bark of M. alba were separated by column chromatography and identified by LC-MS/MS and NMR spectroscopy. The anti-MRSA efficacy of the active ingredients were evaluated by broth microdilution method and a murine infection model. The mode of action of compounds was explored by time-kill curve and post-contact effect. The preliminary mechanism of compounds against MRSA was explored by drug efflux pumps and bacterial biofilms. Chemical isolation resulted in twenty-nine known compounds, most with one or more geranyl and prenyl units exhibited superior anti-MRSA bioactivity, with MIC values of 2–16 μg/mL. In addition, the mode of action indicated that compounds presented persistent antimicrobial effect, which also produced concentration-dependent and time-dependent killing activity or property. Preliminary mechanism showed that the compound kuwanon O (29) damaged the bacterial cell membranes, leading to the accumulation of antibiotics inside bacterial cells, moreover, MA-6 and kuwanon O (29) inhibited the efflux of drugs by combining with methicillin or ethidium bromide (EtBr), resulting in the MICs of EtBr and methicillin were obviously decreased three-fold. The anti-MRSA efficacy in vivo indicated that the active fraction MA-6 could reduce bacteria in spleen, liver, kidney and mortality of acutely infectious mice, which was better than the positive drug berberine chloride. Experimental investigation showed that the MA-6 and compound 29 have promising bioactivity against MRSA in vitro and in vivo , which might be used as a potential source of new antibacterial medicine or a potential efflux pump inhibitor against MRSA infection. [Display omitted] [ABSTRACT FROM AUTHOR]

Prunella vulgaris L. (P. vulgaris) is a medicinal plant belonging to the Labiatae family, and its dried spikes is called as Xiakucao in China, which is a common traditional Chinese medicine with the activities of clearing the liver and expelling fire, improving eyesight, dispersing nodules and detumescence. Modern pharmacological studies have proved that P. vulgaris has various pharmacological activities such as immunomodulatory, antiviral, antibacterial and anti-insomnia activities. P. vulgaris have been reported to have anti-insomnia effects. Nevertheless, the pharmacodynamic substance basis of this anti-insomnia effect is still unclear. The aim of this study was to identify the active components responsible for evoking the anti-insomnia effect of P. vulgaris and to evaluate its anti-insomnia effect. In this study, we proposed a method combined with pharmacodynamic experiments, extraction and enrichment of chemical components, and the plasma pharmacochemistry to screen out the anti-insomnia components of P. vulgaris. Firstly, the active eluted fraction of the ethanol extract was screened out based on pharmacodynamic tracing method, and then the chemical composition was analyzed systematically by UPLC-MS/MS. Thirdly, pharmacodynamic tracing method and silica gel column chromatography were employed to screen out the active fraction of 70% ethanol eluted fraction, and its bioactive components in vitro and in vivo were identified by UPLC-MS/MS. Finally, screening out the anti-insomnia components of P. vulg aris by comparing the difference between in vivo and in vitro components, and three potentially bioactive ingredients were validated experimentally. It was confirmed that the fraction eluted with 70% ethanol from macroporous adsorption resin column was responsible for the anti-insomnia efficacy, and 55 compounds were identified or preliminarily identified. Then totally 9 compounds in vitro and 12 compounds in vivo from the active fraction of 70% ethanol eluted fraction were tentatively identified. Among them, mangiferin, rosmarinic acid and salviaflaside were the prototype components of P. vulgaris , which indicated that the three compounds might play the key role in the anti-insomnia activities. In vivo, compared to blank control group, the three compounds significantly shortened the sleeping latency and prolonged the sleeping time produced by pentobarbital sodium. This study clarified that mangiferin, rosmarinic acid and salviaflaside were considered as the anti-insomnia components of P. vulgaris. This is the first study on screening out the active ingredients responsible for evoking the anti-insomnia effect of P. vulgaris. The three compounds of P. vulgaris may help develop one or more drugs to prevent or treat insomnia. Further investigations are recommended to define the mechanism of the anti-insomnia activity of P. vulgaris. [Display omitted] • 55 compounds were identified from the effective fraction 1 of Prunella vulgaris L by UPLC-MS/MS. • Mangiferin, abscisic acid and daidzein were identified in Prunella vulgaris L. for the first time. • Mangiferin, rosmarinic acid and salviaflaside were considered as the anti-insomnia components of Prunella vulgaris L. [ABSTRACT FROM AUTHOR]

Clematis chinensis Osbeck (C. chinensis), Clematis hexapetala Pall (C. hexapetala) and Clematis terniflora var. mandshurica Rupr (C. mandshurica) are collectively referred to as Clematidis Radix et Rhizome (CRR) in China. CRR is widely distributed in China, which is used as a traditional Chinese medicine to treat rheumatic arthralgia, limb numbness, tendon constriction and inconvenience in flexion and extension. This review systematically summarized the research progress on uses, chemical components, pharmacological activities and toxicology of CRR, listed the chemical structures of main compounds for clarifying the differences in chemical compositions. Meanwhile, the review will provide a theoretical and practical basis for the further research and development of CRR. The available information on CRR was collected using published materials and electronic databases, including ancient and modern books, Chinese Pharmacopoeia, Ph.D. and M. Sc. dissertations, CNKI, SciFinder, WanFang data, PubMed, ScienceDirect and Web of Science. The starting and ending years of references is 1965–2020, the search strategy was conducted by key words such as uses, chemical components, pharmacology and toxicology of CRR. Up to now, CRR has been used to treat various diseases/disorders, such as relieving rheumatism pain, treating cervical spondylopathy and scapulohumeral periarthritis, treating hepatic carcinoma and gastrointestinal, etc. In addition, more than 200 compounds have been isolated from the three plant species of Clematidis. Moreover, the crude extracts and isolated compounds of CRR have been reported to have a wide range of pharmacological activities, such as anti-inflammatory, anti-tumor, antimicrobial and antioxidant activities, etc. Toxicity studies have shown that CRR can cause oral burning, swelling, abdominal pain or severe diarrhea, difficulty breathing, dilated pupils, renal tissue structural changes, and severe death. Researches in recent years mainly focused on C. chinensis and C. mandshurica , while there are a few reports on the pharmacological studies of C. hexapetala. Therefore, it is necessary to conduct further research on C. hexapetala. Meanwhile, it is important to pay attention to pursue research on the similarities and differences between the three plant species of Clematidis to find their respective advantages and make rational use of CRR. In addition, there is no report on the mechanism of toxicity research, which needs more attention. Image 1 • The usage history of Clematidis Radix et Rhizome in China was introduced and Chinese patent medicines containing CRR were listed. • The chemical constituents and structures of Clematidis Radix et Rhizome were summarized. • The research on pharmacological effects and toxicity of Clematidis Radix et Rhizome were summarized. [ABSTRACT FROM AUTHOR]

Danggui Buxue Decoction (DBD), as a classical Chinese medicine prescription, is composed of Danggui (DG) and Huangqi (HQ) at a ratio of 1:5, and it has been used clinically in treating anemia for hundreds of years. The aim of this study was to explore the treatment mechanisms of DBD in anemia rats from the perspective of thymus and spleen. In this study, a successful hemorrhagic anemia model was established, and metabolomics (UPLC-QTOF-MS/MS) and proteomics (label-free approach) together with bioinformatics (Gene Ontology analysis and Reactome pathway enrichment), correlation analysis (pearson correlation matrix) and joint pathway analysis (MetaboAnalyst) were employed to discover the underlying mechanisms of DBD. DBD had a significant blood enrichment effect on hemorrhagic anemia rats. Metabolomics and proteomics results showed that DBD regulated a total of 10 metabolites (lysophosphatidylcholines, etc.) and 41 proteins (myeloperoxidase, etc.) in thymus, and 9 metabolites (L-methionine, etc.) and 24 proteins (transferrin, etc.) in spleen. With GO analysis and Reactome pathway enrichment, DBD mainly improved anti-oxidative stress ability of thymocyte and accelerated oxidative phosphorylation to provide ATP for splenocyte. Phenotype key indexes were strongly and positively associated with most of the differential proteins and metabolites, especially nucleosides, amino acids, Fabp4, Decr1 and Ndufs3. 14 pathways in thymus and 9 pathways in spleen were obtained through joint pathway analysis, in addition, the most influential pathway in thymus was arachidonic acid metabolism, while in spleen was the biosynthesis of phenylalanine, tyrosine and tryptophan. Furthermore, DBD was validated to up-regulate Mpo, Hbb and Cp levels and down-regulate Ca2+ level in thymus, as well as up-regulate Fabp4, Ndufs3, Tf, Decr1 and ATP levels in spleen. DBD might enhance thymus function mainly by reducing excessive lipid metabolism and intracellular Ca2+ level, and promote ATP production in spleen to provide energy. Image 1 [ABSTRACT FROM AUTHOR]