Efficacy and mechanism of action of Yanxiao Di'naer formula for non-alcoholic steatohepatitis treatment based on metabolomics and RNA sequencing.

ETHNOPHARMACOLOGICAL RELEVANCE: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is a crucial component of this disease spectrum. The Yanxiao Di'naer formula (YXDNE) is an Uyghur medical extract that has been used in folk medicine to treat hepatitis for a long time. However, the role and mechanism of action of YXDNE in NASH treatment remains unclear. OBJECTIVE: The objective of this study was to assess the effectiveness of YXDNE in treating NASH induced by injections of carbon tetrachloride combined with a high-fat high-cholesterol diet (HFHCD), and to clarify the underlying mechanisms. METHODS: The compounds in the YXDNE extract were analysed for classification and proportions using ultra-performance liquid chromatography-mass spectrometry. The efficacy of YXDNE in treating abnormal lipid metabolism was evaluated in L02 cells in vitro. In addition, a C57BL/6 mouse model of NASH was established to evaluate the therapeutic efficacy of YXDNE in vivo. Metabolomics and RNA sequencing were used to analyse the therapeutic effects of YXDNE on the liver. The corresponding signalling pathways were found to target AMPKα1, PPARα, and NF-κB. The efficacy of YXDNE was validated using inhibitors or silencing RNA (siRNA) against AMPKα1 and PPARα. RESULTS: This study confirmed that YXDNE treatment ameliorated NASH in a murine model of this disease. Metabolomics analysis suggested that YXDNE efficacy was associated with fatty acid catabolism and AMPK signalling pathways. RNA sequencing results showed that YXDNE efficacy in treating NASH was highly correlated with the AMPK, PPARα and NF-κB pathways. Both in vitro and in vivo experimental data demonstrated that YXDNE affected the expression of p-AMPKα1, PPARα, p-NF-κB, IκB, and p-IκB. The efficacy of YXDNE in treating NASH in vitro was cancelled when AMPK was inhibited with Compound C or PPARα was modulated via siRNA. CONCLUSIONS: YXDNE may have a therapeutic effect on abnormal lipid metabolism in L02 cells and in a murine model of NASH by affecting the AMPKα1/PPARα/NF-κB signalling pathway. Therefore, YXDNE has the potential for clinical application in the prevention and treatment of NASH.

Cistanche tubulosa alleviates ischemic stroke-induced blood-brain barrier damage by modulating microglia-mediated neuroinflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke (IS) has both high morbidity and mortality. Previous research conducted by our group demonstrated that the bioactive ingredients of the traditional medicinal and edible plant Cistanche tubulosa (Schenk) Wight (CT) have various pharmacological effects in treating nervous system diseases. However, the effect of CT on the blood-brain barrier (BBB) after IS are still unknown. AIM OF THE STUDY: This study aimed to identify CT's curative effect on IS and explore its underlying mechanism. MATERIALS AND METHODS: IS injury was established in a rat model of middle cerebral artery occlusion (MCAO). Gavage administration of CT at dosages of 50, 100, and 200 mg/kg/day was carried out for seven consecutive days. Network pharmacology was used for predicting the pathways and potential targets of CT against IS, and subsequent studies confirmed the relevant targets. RESULTS: According to the results, both neurological dysfunction and BBB disruption were exacerbated in the MCAO group. Moreover, CT improved BBB integrity and neurological function and protected against cerebral ischemia injury. Network pharmacology revealed that IS might involve neuroinflammation mediated by microglia. Extensive follow-up studies verified that MCAO caused IS by stimulating the production of inflammatory factors and microglial infiltration. CT was found to influence neuroinflammation via microglial M1-M2 polarization. CONCLUSION: These findings suggested that CT may regulate microglia-mediated neuroinflammation by reducing MCAO-induced IS. The results provide theoretical and experimental evidence for the efficacy of CT therapy and novel concepts for the prevention and treatment of cerebral ischemic injuries.

Assessment of prophylactic antibiotics administration for acute pancreatitis: a meta-analysis of randomized controlled trials.

BACKGROUND: Recent evidence has shown that prophylactic antibiotic treatment in patients with acute pancreatitis is not associated with a significant decrease in mortality or morbidity. The use and efficacy of prophylactic antibiotic treatment in acute pancreatitis remain controversial. This meta-analysis was conducted to assess whether antibiotic prophylaxis is beneficial in patients with acute pancreatitis. METHODS: We searched randomized controlled trials (RCTs) of prophylactic use of antibiotics using Medline (PubMed), Embase, the Cochrane Library, and Web of Science. The data were analyzed using Review Manager 5.3 software. We performed pooled analyses for infected pancreatic necrosis, mortality, surgical intervention, and non-pancreatic infection. Odds ratios (ORs) from each trial were pooled using a random or fixed effects model, depending on the heterogeneity of the included studies. Sub-group analysis or sensitivity analysis was conducted to explore potential sources of heterogeneity, when necessary. RESULTS: Totally, 11 RCTs involving 747 participants were included, with an intervention group (prophylactic use of antibiotics, n = 376) and control group (n = 371). No significant differences were found regarding antibiotic prophylaxis with respect to incidence of infected pancreatic necrosis (OR, 0.74; 95% confidence interval [CI], 0.50-1.09; P = 0.13), surgical intervention (OR, 0.92; 95% CI, 0.62-1.38; P = 0.70), and morality (OR, 0.71; 95% CI, 0.44-1.15; P = 0.16). However, antibiotic prophylaxis was associated with a statistically significant reduction in the incidence of non-pancreatic infection (OR, 0.59; 95% CI, 0.42-0.84; P = 0.004). CONCLUSIONS: Prophylactic antibiotics can reduce the incidence of non-pancreatic infection in patients with AP.

A new cytotoxic isoflavane from Dalbergiae Odoriferae Lignum / 中国中药杂志

Fourteen compounds were isolated from the ethanol extract of Dalbergiae Odoriferae Lignum by various chromatographic techniques, including column chromatographies on silica gel, Sephadex LH-20 and semi-preparative HPLC. Their structures were determined by spectroscopic techniques as S-3'-hydroxy-7,2',4'-trimethoxyisoxane(1), 2-(2',4'-dimethoxyphenyl)-6-hydroxybenzofuran(2), 2-(2'-hydroxy-4'-methoxyphenyl)-6-methoxybenzofuran(3), 7,2',4'-trimethoxydihydroisoflavone(4), sativanone(5), 3,9-dimethoxy-6H-benzofuro[3,2-c]chromen-6-one(6),(6 aS,11 aS)-homopterocarpin(7),(6 aS,11 aS)-8-hydroxy-3,9-dimethoxypterocarpan(8),(6 aS,11 aS)-3,8,9-trimethoxypterocarpan(9), isodalbergin(10), isoliquiritigenin(11), butein(12), butin(13) and 3,7,4'-trihydroxyflavone(14). Among them, compound 1 was a new compound, while 2 and 3 were new natural products, 6, 8, 9 and 14 were isolated for the first time from Dalbergiae Odoriferae Lignum. Compounds 1-14 were tested for their cytotoxic activity against human hepatoma cell line BEL-7402, human gastric cancer cell line SCG-7901, human lung cancer cell line A549, human chronic myeloid leukemia cell line K562 and HeLa human cervical cancer cellline by MTT method. Compound 1 exhibited significant cytotoxicity with IC_(50) values ranging from 2.85 to 11.62 μg·mL~(-1). In addition, 2, 11 and 12 showed weak cytotoxic activities.

A new eudesmane type sesquiterpene from cultivated Clerodendranthus spicatus in Hainan / 中国中药杂志

Six compounds were isolated from the aerial part of cultivated Clerodendranthus spicatus in Hainan with various chromatographic techniques,and their structures were determined as:1-dehydroxy-1-oxo-rupestrinol(1),N-trans-feruloyltyramine(2),methyl 3,4-dihydroxyphenyllactate(3),caffein acid(4),methyl caffeate(5) and ethyl caffeate(6),via analysis of physicochemical properties and spectroscopic evidence.Compound 1 was a new compound,while compounds 2 and 3 were isolated from C.spicatus for the first time.Biological activity results showed that compounds 2-4 exhibited α-glucosidase inhibitory activity with different inhibition ratio.

Study on sesquiterpenes from agarwood originating from Gyrinops salicifolia / 中国中药杂志

Two sesquiterpenes were isolated from the agarwood originating from Gyrinops salicifolia with various chromatographic techniques, and their structures were determined as 12-hydroxy-dihydrocyperolone(1) and(rel)-4β,5β,7β-eremophil-9-en-12,8α-olide(2), through a combined analysis of physicochemical properties and spectroscopic evidence. Compound 1 was a new compound. Compound 2 showed cytotoxicities against K562 and BEL-7401 cell lines, with IC_(50) values of(17.85±0.04) and(21.82±0.07) mg·L~(-1), respectively [taxol as positive control, with IC_(50) values of(1.97±0.11) and(6.31±0.08) mg·L~(-1)].

A new sesquiterpene from Chinese agarwood induced by artificial holing / 中国中药杂志

In order to study the chemical constituents of n-butanol fraction of ethanol extract from Chinese agarwood induced by artificial holing, various chromatographic techniques were carried out to isolate compounds, and the structures of compounds were determined through a combined analysis of physicochemical properties and spectroscopic evidence. Seven compounds were obtained and identified as selina-3,11-dien-9,15-diol (1), aquilarone D (2), 5α,6β,7α,8β-tetrahydroxy-2-[2-(2-hydroxyphenyl)ethyl]-5,6,7,8-tetrahydrochromone (3), 6,7-dimethoxy-2-[2-(4-methoxyphenyl)ethyl]chromone (4), syringin (5), methyl (Z)-p-coumarate (6), and 4'-methoxycinnamic acid (7), among which compound 1 was a new compound and compounds 5-7 were isolated from agarwood for the first time. The bioactivity assay results concluded that compounds 6 and 7 showed certain nematicidal activity against Panagrellus redivivus, and compounds 4, 6 and 7 exhibited cytotoxicity against BEL-7402, SGC-7901 and A549 carcinoma cell lines.

Antibacterial components from artificially induced dragon's blood of Dracaena cambodiana / 中国中药杂志

Ten compounds were isolated from the artificially induced dragon's blood of Dracaena cambodiana by various column chromatographies on silica and sephadex LH-20 gel. Based on spectral analysis of NMR and MS, their structures were identified as 3, 4-dihydroxyallylbenzene (1), 3', 4', 5'-trimethoxycinnamylalcohol (2), pinoresinol (3), (2R)-7, 4'-dihydroxy-8-methylflavane (4), (2R)-7,4'-dihydroxy-5-methoxy-8-methylflavane(5),(2S)-7,3'-dihydroxy-4'-methoxy-8-methylflavane(6) ,(2S)-4',7-dihydroxy-6, 8-dimethylflavane(7), 4,2',4'-trihydroxychalcone(8), 4,4'-dihydroxy-2-methoxydihydrochalcon(9) and Cambodianin E (10). Antibacterial activity assay showed that compounds 1, 4 and 10 have inhibitory effect on Fusarium oxysporum f. sp. cuben, Fusarium oxysporum f. sp. niveum, Fusarium oxysporum f. sp. vasinfectum and Ralstonia solanacearum.

Synergism and rules of the new combination drug Yiqijiedu formulae (YQJD) on ischemic stroke based on amino acids (AAs) metabolism.

The use of combination drugs is considered to be a promising strategy to control complex diseases such as ischemic stroke. The detection of metabolites has been used as a versatile tool to reveal the potential mechanism of diverse diseases. In this study, the levels of 12 endogenous AAs were simultaneously determined quantitatively in the MCAO rat brain using RRLC-QQQ method. Seven AAs were chosen as the potential biomarkers, and using PLS-DA analysis, the effects of the new combination drug YQJD, which is composed of ginsenosides, berberine, and jasminoidin, on those 7 AAs were evaluated. Four AAs, glutamic acid, homocysteine, methionine, and tryptophan, which changed significantly in the YQJD-treated groups compared to the vehicle groups (P < 0.05), were identified and designated as the AAs to use to further explore the synergism of YQJD. The result of a PCA showed that the combination of these three drugs exhibits the strongest synergistic effect compared to other combination groups and that ginsenosides might play a pivotal role, especially when combined with jasminoidin. We successfully explored the synergetic mechanism of multi-component and provided a new method for evaluating the integrated effects of combination drugs in the treatment of complex diseases.

Metabolites from the endophytic fungus HP-1 of Chinese eaglewood / 中国天然药物

AIM@#To study the chemical constituents from the fermentation of the endophytic fungus HP-1 of Chinese eaglewood.@*METHODS@#The chemical constituents were isolated by column chromatography on silica gel and Sephadex LH-20, and their structures were elucidated on the basis of spectroscopic analysis.@*RESULTS@#Four compounds were isolated and identified as 3α, 3β, 10β-trimethyl-decahydroazuleno[6, 7]furan-8, 9, 14-triol (1), 4-hydroxyphenylacetic acid (2), 4-hydroxyphenethyl alcohol (3), and 5-hydroxymethyl-2-furancarboxaldehyde (4).@*CONCLUSION@#Compound 1 was a new compound. Compound 2 showed antibacterial activity against Staphylococcus aureus.

A new diterpene from the stems of Trigonostemon heterophyllus / 中国天然药物

AIM@#To investigate the chemical constituents in the stems of Trigonostemon heterophyllus.@*METHOD@#The chemical constituents were isolated by column chromatography on silica gel, Rp-18, and Sephadex LH-20, and their structures were elucidated on the basis of spectroscopic analysis.@*RESULTS@#Three compounds were isolated and identified as a new diterpene, trigonoheterene B (1), together with two known compounds, trigonostemone (2) and trigonochinene B (3).@*CONCLUSION@#Compound 1 is new. Compounds 2 and 3 showed antibacterial activities.

Chemical constituents of Dalbergia odorifera / 中国中药杂志

Fourteen compounds were isolated from Dalbergia odoriferae and purified by repeated column chromatography on silica and sephadex LH-20 gel and structurally identified by spectral analysis. These compounds were identified as 4, 9-dimethoxy-3-hydroxypterocarpan (1), medicarpin (2), 2', 4', 5-trihydroxy-7-methoxyisoflavone (3), 2', 3', 7-trihydroxy-4'-methoxyisoflavan (4), formononetin (5), 3, 8-dihydroxy-9-methoxypterocarpan (6), koparin (7), 3-hydroxy-9-methoxypterocarp-6a-ene (8), 2'-hydroxyformononetin (9), stevenin (10), 2', 7-dihydroxy-4', 5'-dimethoxyisoflavone (11), lyoniresinol (12), 2, 4-dihydroxy-5-methoxy-benzophenone (13) and neokhriol A (14). Compounds 1, 3, 4, 6, 8, 12 and 14 were isolated from this plant for the first time. Antibacterial activity assay showed that compound 4 had inhibitory effect on Ralstonia solanacearum.

Metabolites from the endophytic fungus Penicillium sp. FJ-1 of Ceriops tagal / 药学学报

To investigate the chemical constituents of the endophytic fungus Penicillium sp. FJ-1 of Ceriops tagal, the chemical constituents were isolated by column chromatography on silica gel and Sephadex LH-20. Their structures were elucidated on the basis of spectroscopic analysis. Their antibacterial activity was tested by paper disco diffusion method. Two compounds were isolated and identified as 7-hydroxy-deoxytalaroflavone (1), and deoxytalaroflavone (2). Compound 1 is a new compound, and compounds 1 and 2 showed weak activity against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus.

Chemical constituents from stems of Aquilaria sinensis / 中国中药杂志

<p><b>OBJECTIVE</b>To study the constituents from the stems of Aquilaria sinensis.</p><p><b>METHOD</b>The chemical constituents were isolated by various column chromatographic methods. The structures were identified by spectral analysis including NMR and MS data.</p><p><b>RESULT</b>Sixteen compounds were isolated and identified as threo-buddlenol C (1), thero-ficusesquilignan A (2), erythro-buddlenol C (3), (+/-) buddlenol D (4), (-) medioresinol (5), (-) pinoresinol (6), 5'-methoxy lariciresinol (7), erythro-guaiacylglycerol-beta-coniferyl ether (8), thero-guaiacylglycerol-beta-coniferyl ether (9), herpetin (10), (+) syringaresinol (11), curuilignan (12), ciwujiatone (13), coniferyl alcohol (14), 3, 4, 5-trimethoxyphenol (15) and cucurbitacin (16).</p><p><b>CONCLUSION</b>All the compounds, except for 11-13 were obtained from A. sinensis for the first time.</p>

Toxicarioside A, isolated from tropical Antiaris toxicaria, blocks endoglin/TGF-β signaling in a bone marrow stromal cell line

OBJECTIVE@#To investigate possible mechanism of toxicarioside A in HS-5 bone stromal cells.@*METHODS@#HS-5 bone stromal cells were cultured in media supplemented with various concentrations of toxicarioside A or control DMSO (not treatment). Endoglin and TGF-β were detected by Northern and Western blot analysis and quantified in a standard method. Downstream molecules of endoglin and TGF-β (Smad1, Smad2 and their active phosphorylated counterparts, pSmad1 and pSmad2) were also detected and quantified by Western blot analysis. In addition, cell proliferation assay and small interfering RNA (siRNA) against endoglin were used to certificate the function of endolgin in the HS-5 cells.@*RESULTS@#Compared with the not treated (0 μg/mL) or DMSO treated control HS-5 cells, HS-5 cells treated with toxicarioside A were found significant attenuation of endolgin and TGF-β expression. Significant inhibition of cell proliferation was also found in the HS-5 cells treated with toxicarioside A. ALK1-related Smad1 and ALK5-related Smad2 were decreased in HS-5 cells treated with toxicarioside A. In addition, phosphorylated Smad1 (pSmad1) and Smad2 (pSmad2) were also found attenuation in toxicarioside A-treated HS-5 cells. RNA interference showed that blockage of endoglin by siRNA also decreased Smad1 and Smad2 expression in HS-5 cells.@*CONCLUSIONS@#Our results indicate that toxicarioside A can influence bone marrow stromal HS-5's function and inhibit HS-5 cell proliferation by alteration of endoglin-related ALK1 (Smad1) and ALK5 (Smad2) signaling.

Cytochalasin D, a tropical fungal metabolite, inhibits CT26 tumor growth and angiogenesis

OBJECTIVE@#To investigate whether cytochalasin D can induce antitumor activities in a tumor model.@*METHODS@#Murine CT26 colorectal carcinoma cells were cultured in vitro and cytochalasin D was used as a cytotoxic agent to detect its capabilities of inhibiting CT26 cell proliferation and inducing cell apoptosis by MTT and a TUNEL-based apoptosis assay. Murine CT26 tumor model was established to observe the tumor growth and survival time. Tumor tissues were used to detect the microvessel density by immunohistochemistry. In addition, alginate encapsulated tumor cell assay was used to quantify the tumor angiogenesis in vivo.@*RESULTS@#Cytochalasin D inhibited CT26 tumor cell proliferation in time and dose dependent manner and induced significant CT26 cell apoptosis, which almost reached the level induced by the positive control nuclease. The optimum effective dose of cytochalasin D for in vivo therapy was about 50 mg/kg. Cytochalasin D in vivo treatment significantly inhibited tumor growth and prolonged the survival times in CT26 tumor-bearing mice. The results of immunohistochemistry analysis and alginate encapsulation assay indicated that the cytochalasin D could effectively inhibited tumor angiogenesis.@*CONCLUSIONS@#Cytochalasin D inhibits CT26 tumor growth potentially through inhibition of cell proliferation, induction of cell apoptosis and suppression of tumor angiogenesis.

Screening of Antitumor and Antimicrobial Activities of the Endophytic Fungi Isolated from Cephalotaxus hainanensis Li / 微生物学通报

Seventy-two endophytic fungi isolated from Cephalotaxus hainanensis Li were screened for antitumor and antimicrobial activities. The results showed that 9 strains presented cytotoxic activities to at least one of the tested tumor cells, five strains exhibited strong antimicrobial activity against Staphylococcus aureus, one strain had inhibitory effect on Phytophthora parasitica. It was evidently that the endophytic fungi of C. hainanensis are potential resources to find valuable bioactive components.

Isolation and Primary Identification of Endophytic Fungi from Cephalotaxus hainanensis L / 微生物学通报

Seventy-two strains of endophytic fungi were isolated from the healthy bark, branches and leaves of Cephalotaxus hainanensis L.. Sixty-eight of them were morphologically classified into Fungi Imperfecti, thirty-three sporulated were identified to five genera. For those did not sporulate, one was identified to Rhizoctonia sp., the rest were tentatively classified into Mycelia Sterilia. Four were identified to Basidiomycetes. The result indicated the endophytic fungi of C. hainanensis show a degree of tissue specificity. There were significant differences about the quantity, genera and composition between the fungi isolated from bark and those from branches and leaves.

Volatile Oil Constituents of Two Acremonium Endophyte Isolates from Aquilaria sinensis / 微生物学通报

The volatile oils of endophyte isolates R1 (Acremonium sp.) and R2 (Acremonium sp.) from Aqui-laria sinensis were extracted by solvent method. Twenty and sixteen ingredients were identified from the volatile oils of R1 and R2 by GC-MS, respectively. Fatty acids, such as oleic acid, linoleic acid, hexa-decanoic acid etc., were the main components, whereas terpenoids like 1,8-cineole, zingiberene, ar-curcumene were also found in both oils. It’s the first report about the volatile oil constituents of endophyte isolates from A. sinensis.

Study on Cytotoxic Activity and Chemical Constitunents of Marine Actinomycets Strain 124092 / 微生物学通报

The hexane extract from marine actinomycetes 124092 showed potent inhibition on B16 cell line by MTT assay. The hexane extract was fractionationed on silica gel column by vacuum liquid chromatography to afford 6 fractions(Fr1~Fr6), and Fr6 showed cytotoxic activity. To determine the bioacitve components of hexane extract, Fr6 was analyzed by GC/MS. The main components were identified as palmitic acid (11.76%), oleic acid (12.16%), linoleic acid (14.77%), and lactobacillic acid (61.31%). It have been reported that palmitic acid, oleic acid, and linoleic acid possess cytotoxic activity on rat ascites tumor cells and linoleic acid have suppressive effect on human lung adenocarcinoma cells.