[Research progress on natural products of fungi of Diaporthe sp.]

Diaporthe sp. fungi is one of the important sources of active natural products. Polyketides, alkaloids, terpenes, anthraquinones and other types of novel metabolic products are found from this genus, and many of them have significant anti-tumor, antibacterial, anti-hyperlipidemia, inhibition of pulmonary fibrosis, antioxidant and other biological activities. This paper reviewed source, structure and biological activity of natural products from Diaporthe sp. in the past two decades, and provided a reference for in-depth study of natural product of this genus fungus and innovative drug development.

[Research progress on sesquiterpenes and its pharmacological activities in genus Carpesium].

The genus Carpesium plants contain many kinds of sesquiterpenes. Up to now, more than 201 sesquiterpene compounds have been isolated and identified, including 86 germacranolides, 30 eudesmanolides, 29 guaianolides, 23 sesquiterpene dimers, 9 pseudoguaianes, 9 carabranolides, 7 xanthanolides, 6 sesquiterpenes without lactone, 1 eremophilane and 1 tricyclo dodecane sesquiterpene. The reported sesquiterpenes possess a series of pharmacological properties, such as anti-tumor, anti-inflammatory, antibacterial, antiparasitic, insecticidal, and antiviral activities. This paper summarizes the 201 chemical structures and biological activities of sesquiterpenes in genus Carpesium, and provides the scientific basis for the further development and utilization.

New Risk Factors for Infected Pancreatic Necrosis Secondary to Severe Acute Pancreatitis: The Role of Initial Contrast-Enhanced Computed Tomography.

BACKGROUND AND AIMS: Pancreatic necrosis is a risk factor for poor prognosis of acute pancreatitis (AP). However, the associations between the findings on initial contrast-enhanced computed tomography (CT) of the pancreas and infected pancreatic necrosis (IPN) are unclear. METHODS: This was a retrospective cohort study. Patients with severe AP (SAP) from January 2014 to December 2016 at the First Affiliated Hospital of Nanchang University were enrolled and assigned to an IPN group and a non-IPN group. Univariate and multivariate logistic regression analyses were sequentially performed to assess the associations between the variables and IPN development. A receiver operating characteristic (ROC) curve was generated for the qualified independent risk factor. RESULTS: Forty-two patients with IPN were compared with 100 patients without IPN. Contrast-enhanced CT was performed 7 (range 3-10) days after AP onset. Multivariate stepwise logistic regression analyses showed that the number of acute peripancreatic fluid collections (APFCs) (OR 1.328, P = 0.006), presence of peripancreatic and pancreatic parenchymal necrosis (OR 4.001, P = 0.001), and gastrointestinal wall thickening (OR 3.353, P = 0.006) were independent risk factors for IPN secondary to SAP. The area under an ROC curve for the number of APFCs was 0.714, the sensitivity was 78.60%, and the specificity was 57.30% at a cutoff value of 4.5. CONCLUSIONS: The number of APFCs, presence of peripancreatic and pancreatic parenchymal necrosis, and gastrointestinal wall thickening were independent risk factors associated with IPN. As initial contrast-enhanced CT (about 7 days from AP onset) plays an important role in predicting IPN, it is important for clinicians to consider initial imaging of the pancreas.

Proteomic Analysis of the Antidepressant Effects of Shen-Zhi-Ling in Depressed Patients: Identification of Proteins Associated with Platelet Activation and Lipid Metabolism.

Shen-Zhi-Ling (SZL) is a Chinese medicine formulated from a Kai-Xin-San decoction that is commonly used to treat depression caused by dual deficiencies in the heart and spleen. However, the underlying mechanisms remain unclear. We investigated biological changes in depression patients (DPs) exhibiting antidepressant responses to SZL treatment using proteomic techniques. We performed label-free quantitative proteomic analysis and liquid chromatography-tandem mass spectrometry to discover and examine altered proteins involved in depression and antidepressant treatment. Serum samples were collected from DPs, DPs who underwent 8 weeks of SZL treatment and healthy controls (HCs). The proteins that differed among the three groups were further validated by Western blot analysis. By performing multivariate analyses, we identified 12 potential serum biomarkers that were differentially expressed among the HC, DP, and SZL groups. We then confirmed the significant changes in alpha-1-antitrypsin, von Willebrand factors, apolipoprotein C-III, and alpha-2-macroglobulin among the three groups by performing Western blot analysis, which supported the proteomic results. Profiling the proteomic changes in DPs treated with SZL could improve our understanding of the pathways involved in SZL responses, such as alterations in platelet activation, inflammatory regulation, and lipid metabolism. Future studies involving larger patient cohorts are necessary to draw more definitive conclusions.

[Isolation of endophytic fungi from Zanthoxylum simulans and screening of its active strain].

This study aims at making full use of microbial resources, and screening the active endophytic fungi of anti-rheumatoid arthritis from Zanthoxylum simulans. The endophytic fungi were cultured and isolated by tissue culture and scribing method, and the active strain of inhibiting the proliferation of human rheumatoid arthritis synovial fibroblasts (HFLS-RA) was screened by MTT method. Morphological characteristics and rDNA ITS1-5.8S-ITS2 sequences were applied for the taxonomy of endophytic fungi. Strains were isolated from Z. simulans. Among them, MK-05, MK-17, MK-19, MK-23 having inhibiting activity to HFLS-RA, the IC50 were 0.367, 0.775, 0.689, 0.757 g·L⁻¹, respectively. By classic morphologic classification and sequencing the PCR-amplified rDNA ITS1-5.8S-ITS2 regions, four effective strains were identified as Botryosphaeria dothidea, Phomopsis sp., P. liquidambari and Diaporthe perseae. The active endophyic fungi that inhibited the proliferation of HFLS-RA were screened from Z. simulans for the first time, and the results lay the foundation for the development and utilization of the Z. simulans resources.

[Study on effects of total saponins from Lilii Bulbus on proliferation, apoptosis, invasion and metastasis of lung cancer cells and its preliminary mechanism].

The potential role of total saponins extracted from Lilium lancifolium bulbs (TSLL) on the proliferation, apoptosis, migration and invasion of human lung cancer A549 cells and its possible mechanism were discussed. Effect of TSLL on proliferation of A549 cells were detected by CCK-8, clone formation assay and EdU staining. Effect of TSLL on apoptosis morphology of A549 cells was observed by fluorescence microscope using Annexin V/PI double staining and Hoechst 33342 staining. Effect of TSLL on cell migration and invasion was detected by Transwell migration test and Transwell invasion test, respectively. Western blot was used to detect TSLL on the expression change of intracellular associated proteins. Results showed that TSLL intervention in A549 cells within 24, 48 or 72 h significantly inhibited cell growth, and its IC50values were about 229, 173 and 71 mg·L⁻¹, respectively. TSLL significantly reduced the clone formation rate of A549 cells and decreased the DNA synthesis rate of A549 cells in a concentration dependent manner. TSLL induced A549 cells apoptosis and reduced the migratory behavior of A549 cells. TSLL decreased invasion of A549 cells to the artificial basement membrane. The expression level of intracellular PCNA and the ratio of Bcl-2/Bax protein were down-regulated and procaspase 3 was activated. In addition, TSLL had no obvious effect on epithelial mesenchymal transition (EMT) related marker proteins E-cadherin and vimentin expression. The above results indicated that TSLL possess inhibitory effects against proliferation, migration and invasion of lung cancer A549 cells and apoptosis-induced effect. The anti-proliferation effect of TSLL is very likely by inhibiting intracellular DNA synthesis through reducing the expression of PCNA in lung cancer cells. And the apoptosis induction of TSLL on lung cancer cells is associated with the regulation of Bcl-2 and Bax proteins expression. Nevertheless, there is no incontestable correlation between anti-invasion and metastasis effects of TSLL and EMT in lung cancer cells.

[Advances in studies on steroidal saponins and their pharmacological activities in genus Lilium].

Genus Lilium plants contain a variety of steroidal saponins, so far at least 82 steroidal saponins have been found in the bulbs of Lilium species, including 13 spirostanol saponins (1-13), 39 isospirostanol saponins (14-52), 7 pseudospirostanol saponins (53-59), and 23 furostanol saponins (60-82). Studies have showed that these steroidal saponins exhibit a wide range of pharmacological activities, including antitumor, antibacterial, antiinflammatory, antioxidant, antidepressant, hepatoprotective, hypoglycemic, sedative-hypnotic effect, and inhibition of cAMP phosphodiesterase and Na⁺-K⁺ ATP, et al. This paper has classified and summarized the 82 steroidal saponins isolated and identified from the bulbs of Lilium species and their correlative biological activities. Also, their structural characteristics and structure-activities relationship have been discussed, which could provide references for further research and application development of Lilium plants.

Value of Raw Rhubarb Solution in the Precaution of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis in Patients with High-Risk Factors: A Predictive Random Compared Research in One Center.

BACKGROUND AND AIMS: Post-ERCP pancreatitis and hyperamylasemia are common complications of endoscopic retrograde cholangiopancreatography (ERCP), especially in high-risk patients. The aim of this study is to evaluate whether a raw rhubarb solution can reduce the incidence of PEP and post-ERCP hyperamylasemia. METHODS: From October 2012 to October 2013, 2100 patients received ERCP in our Endoscopic Center. Five hundred patients with high-risk factors were enrolled randomly into the raw rhubarb group (RG, 250 cases drank a raw rhubarb soak solution per 3 h until defecation after ERCP) and the control group (CG, 250 cases drank water after ERCP) in the study. The serum amylase concentration was measured. The abdominal pain, purge time and symptoms of patients were observed in the two groups. RESULTS: There were no differences in patient demographics, medical history, ERCP procedure, and patient- and procedure-related high-risk factors between the two groups. PEP incidence was 2% (5/250) in the RG group, which was lower than that in the CG group (7.6%, 19/250) (P < 0.01). The rate of post-ERCP hyperamylasemia was 5.2% (13/250) and 16.8% (42/250) in the RG group and CG group, respectively. The incidence of hyperamylasemia in the RG group was significantly lower than that in the CG group (P < 0.01). The incidence of abdominal pain 24 h after ERCP in the RG group was lower than that in the CG group (P < 0.01). No side effects were observed for raw rhubarb solution. CONCLUSIONS: A raw rhubarb solution is safe and effective in preventing the incidence of PEP and hyperamylasemia in high-risk patients.

Antitubercular and cytotoxic tigliane-type diterpenoids from Croton tiglium.

Five new tigliane diterpene esters (1-5), highly oxygenated tetracyclic diterpenoid carbon skeleton, together with three known analogues (6-8) were isolated from the leaves of Croton tiglium. Extensive NMR and mass spectroscopic analysis were used to elucidate their structures. Most of the isolated compounds were tested for their cytotoxic and antitubercular activities. Among them, the cytotoxic activities of these tigliane-type diterpenes strongly depend on the species of the tumor cells. Especially, these bioactivity compounds showed strong cytotoxic activities against the K562 cell line, and their inhibition effects were close to the positive control Taxol. Furthermore, compounds 1, 2, 6, and 7 showed potent antitubercular activities with MIC values of 19.5, 20.9, 20.5, and 13.4µM, respectively.

Single-channel endoscopic closure of large endoscopy-related perforations.

BACKGROUND AND STUDY AIMS: Gastrointestinal endoscopy procedures, such as endoscopic retrograde cholangiopancreatography (ERCP), endoscopic submucosal dissection (ESD), and colonoscopy are widely used for the diagnosis or treatment of digestive diseases. Perforation is a rare but potentially lethal complication. Large perforations usually require immediate endoscopic or surgical repair. Endoscopic closure using a nylon loop pouch suture is usually performed with a double-channel endoscope. This paper describes the endoscopic closure of large procedure-related perforations using a single-channel endoscope. PATIENTS AND METHODS: A total of 10 patients with large perforations (2.5 - 4.0 cm), which occurred during ERCP, ESD, or colonoscopy, were treated using the single-channel endoscope technique. RESULTS: All perforations were successfully closed using a nylon loop pouch suture through the single-channel endoscope. No surgery or further endoscopic intervention was required. CONCLUSIONS: Nylon loop pouch suture through a single-channel endoscope was easy to perform and was feasible for the closure of large gastrointestinal perforations.

AG4, a compound isolated from Radix Ardisiae Gigantifoliae, induces apoptosis in human nasopharyngeal cancer CNE cells through intrinsic and extrinsic apoptosis pathways.

3ß-O-{α-L-Pyran rhamnose-(1→3)-[ß-D-xylopyranose-(1→2)]-ß-D-glucopyranose-(1→4)-[ß-D-lucopyranose-(1→2)]-α-L-pyran arabinose}-cyclamiretin A (AG4) is a saponin component obtained from the Giantleaf Ardisia Rhizome (Rhizoma Ardisiae Gigantifoliae). The present study aimed to investigate the antitumor potential of AG4 and its possible mechanisms in human nasopharyngeal carcinoma cells (CNE). We exposed tumor cells to AG4 to investigate which cell line was the most sensitive to AG4. Cell viability was assessed using the MTT reduction assay, and the effects of AG4 on apoptosis, reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP), and cell cycle were detected using a flow cytometer; the glutathione, superoxide dismutase and malondialdehyde activities were measured using colorimetric methods. The relative expressions of Bax, Bad, Bid, Bcl-2, and Fas mRNA were calculated using the (Equation is included in full-text article.)comparative method by real-time PCR studies and protein was detected by western blotting. AG4 markedly inhibited the growth of CNE cells by decreasing cell proliferation, inducing apoptosis, and blocking the cell cycle in the S phase. The release of caspase-3, caspase-8, and caspase-9 was stimulated by AG4 in CNE, and the decreased proliferation induced by AG4 was blocked by the inhibitor of pan caspase (Z-VAD-FMK). Moreover, the MMP was decreased in AG4-treated cells, and AG4-induced cell apoptosis was accompanied by a rapid and lasting increase in ROS, which was abolished by N-acetyl-L-cysteine (NAC); glutathione, superoxide dismutase, and malondialdehyde were regulated by AG4. AG4 inhibited Bcl-2 mRNA and protein expression and stimulated Bax, Bad, Bid, Fas mRNA, and protein expression in CNE cultures, suggesting an effect at the transcriptional and protein level. In addition, both the FasL inhibitor (AF-016) and the Bcl-2 family inhibitor (GX15-070) could prevent the cell apoptosis induced by AG4. The findings suggested that AG4-induced apoptosis in CNE cells involved a death receptor pathway and a Bcl-2 family-mediated mitochondrial signaling pathway by decreasing the MMPs in an ROS-dependent manner and regulating genes and proteins relative to apoptosis; also, regulation of cell cycles may also play a role in the antitumor mechanism of AG4.

Dicarabrol, a new dimeric sesquiterpene from Carpesium abrotanoides L.

A new dimeric sesquiterpene, dicarabrol (1), together with three known sesquiterpenes, carabrol (2), 11(13)-dehydroivaxillin (3), and 2-desoxy-4-epi-pulchellin (4), were isolated from the whole plant of Carpesium abrotanoides L. Their structures were elucidated on the basis of spectroscopic analysis, and single crystal X-ray diffraction analysis. Compound 1 possessed a dimeric sesquiterpene core featured with a cyclopentane ring connecting two sesquiterpene lactone units rarely discovered in nature. Dicarabrol (1), as well as three known sesquiterpenes (2-4), had potent in vitro cytotoxicities against the K562, MCF-7, Hela, DU145, U937, H1975, SGC-7901, A549, MOLT-4, and HL60 cell lines with IC50 values ranging from 0.10 to 46.7 µM, while they showed significant antiviral (H1N1 and H3N2) activities. Furthermore, compounds 1, 3 and 4 displayed significant antimycobacterial activity (IC50 3.7, 6.0, and 7.6 µM, respectively).

Five new phorbol esters with cytotoxic and selective anti-inflammatory activities from Croton tiglium.

Five new phorbol esters, (four phorbol diesters, 1-4, and one 4-deoxy-4α-phorbol diester, 5), as well as four known phorbol esters analogues (6-9) were isolated and identified from the branches and leaves of Croton tiglium. Their structures were elucidated mainly by extensive NMR spectroscopic, and mass spectrometric analysis. Among them, compound (1) was the first example of a naturally occurring phorbol ester with the 20-aldehyde group. Compounds 2-5, and 7-9 showed potent cytotoxicity against the K562, A549, DU145, H1975, MCF-7, U937, SGC-7901, HL60, Hela, and MOLT-4 cell lines, with IC50 values ranging from 1.0 to 43 µM, while none of the compounds exhibited cytotoxic effects on normal human cell lines 293T and LX-2, respectively. In addition, compound 3 exhibited moderate COX-1 and COX-2 inhibition, with IC50 values of 0.14 and 8.5 µM, respectively.

Lignans from the bark of Zanthoxylum simulans.

Investigation on the EtOAc extract of the bark of Zanthoxylum simulans led to the isolation of four new lignans including zanthoxylumin A (1), zanthoxylumin B (2), ( - )-magnolin (3), and ( - )-pinoresinol-di-3,3-dimethylallyl ether (4). Their structures were established by comprehensive analysis of the spectral data, especially 1D and 2D NMR spectra.

[Simultaneous determination of five sesquiterpene lactones in Carpesium abrotanoides by HPLC].

An HPLC method was established to simultaneously determine the five sesquiterpene lactones, carabrone, carabrol, 2-desoxy-4-epi-pulchellin, telekinand 11(13)-dehydroivaxillin in Carpesium abrotanoides. Samples were analyzed on a kromasil C18 column (4.6 mm x 250 mm, 5 µm); mobile phase: A was acetonitrile, B was water, with gradient elution; flow speed: 1.0 mL · min(-1); detection was carried out using a photodiode array detector at 211 nm; temperatureof column: 30 °C. The five sesquiterpene lactones were well separated with good linear correlations in the range of 0.270-2.700 (r = 0.999 7 ), 1.336-13.360 (r = 0.999 6), 0.258-2.580 (r = 0.999 7), 0.238-2.380 (r = 0.999 9), 0.490-4.900 µg (r = 0.999 9) for carabrone, carabrol, 2-desoxy-4-epi-pulchellin, telekin and 11 (13) -dehydroivaxillin. The average recoveries of these five sesquiterpene lactoneswere 96.78%-98.41% (RSD 1.3%-2.9%). The method was simple, repeatable and stable, which could be used for quality control of C. abrotanoide.

A new dimeric lignan from Zanthoxylum simulans.

To study the chemical constituents from Zanthoxylum simulans and their anti-inflammatory activity. The constituents of Z. simulans were isolated and purified using various column chromatographies. Their chemical structures were elucidated using extensive spectroscopic methods. The compounds were assayed inhibitory activity against NO production in LPS stimulated RAW 264.7 cells. Four compounds were obtained from the ethanol extract of Z. simulans and determined to be isozanthpodocarpin B(1), kobusin (2), (+)-fargesin (3), and epieudesmin (4). Compound 1 exhibited NO production inhibitory effect with IC50 value of 14.49 µmol · L(-1). Compound 1 is a new dimeric lignan and may be serve as potential anti-inflammatory agent in the future.

[Study on Chemical Constituents from Ethyl Acetate Extraction of Sanicula lamelligera].

OBJECTIVE: To study the chemical constituents from ethyl acetate extraction of Sanicula lamelligera. METHODS: Compounds were isolated and purified by silica gel and Sephadex LH-20 column chromatographic method, and their structures were identified by using spectroscopic analysis. RESULTS: Nine compounds were isolated and identified as angelicin (I), isoferulaldehyde (II), 12- hydroxybakuchiol (III), 22-angeloyl-R1-barrigenol (IV), 5,6,7,8,4'-pentamethoxyflavone (V),3,5,6,7,8,3',4'-heptamethoxyflavone (VI), isobavachin (VII), isoliquiritigenin (VIII) and furano (2",3",7,6) 4'-hydroxyflavanone (IX). CONCLUSION: All compounds are isolated from this plant for the first time.

Characterization and biological evaluation of six new dimeric lignans with an unusual α,ß-unsaturated ketone motif from Zanthoxylum simulans.

Investigation of the bark of Zanthoxylum simulans afforded six new dimeric lignans zanthpodocarpins C-H (1-6) bearing an unusual α,ß-unsaturated ketone group. The new structures of 1-6 were determined by using detailed spectroscopic analysis. All of the isolated compounds were examined for their inhibitory effects against rat joint synovial cell and splenocyte proliferation. Compounds 1-6 showed potent anti-inflammatory activities with IC50 values ranging from 18.6 to 36.1µM, and 13.8 to 74.3µM.

Antidepressant and neuroprotective effect of the Chinese herb kaixinsan against lentiviral shRNA knockdown brain-derived neurotrophic factor-induced injury in vitro and in vivo.

Depression has been associated with reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. Previous studies have demonstrated that the herbal medicine formula, 'kaixinsan' (KXS), could ameliorate the severity of depression and increase cAMP response element-binding protein expression. There is direct evidence suggesting that the reduction of the BDNF protein in specific brain sites can provoke depressive-like behaviour or affect neurogenesis in vivo. However, the biological mechanisms between the antidepressant and neuroprotective effect of KXS and the alterations in BDNF levels in in vivo and in vitro models remain unclear. Using BDNF knockdown mediated by lentiviral vectors (LV-shBDNF-3) transfected with primary hippocampal neurons and following injection into the dentate gyrus of the hippocampus, it was demonstrated that a reduction in BDNF expression affects cell viability and animal behaviours associated with depression. During treatment with KXS after the lentiviral shRNA silencing of BDNF in cell and animal, cell viability, body weight, the sucrose preference test (SPT), the open field test (OFT) the Morris Water Maze (MWM) task and BDNF expression were measured. KXS attenuated LV-shBDNF-3-induced cell death in primary hippocampal neurons and also improved the sucrose intake in SPT, ambulatory response in OFT and learning ability in MWM against LV-shBDNF-3-induced depressive-like syndromes. Moreover, immunoblot analysis confirmed that KXS could reverse LV-shBDNF-induced BDNF reduction either in vitro or in vivo. These findings provide substantial evidence for supporting a neurotrophic hypothesis of depression and specify BDNF targets for potential antidepressant interventions. Moreover, the antagonism between LV-shRNA BDNF knockdown and KXS may depend on multiple compounds with synergistic mechanisms that modulate the different signal transduction networks directly or indirectly, increasing BDNF expression and exerting its neuroprotective and antidepressant-like effects.

[Study on Chemical Constituents from Carpesium abrotanoides].

OBJECTIVE: To study the chemical constituents from Carpesium abrotanoides. METHODS: Compounds were isolated and pu- rified by silica gel and Sephadex LH-20 column chromatography, their structures were determined by using spectroscopic analysis. RESULTS: Ten compounds were isolated and identified as Vomifoliol (I), 2-Desoxy-4-epi-pulchellin (II), 8-epi-Confertin (III), 1-epi-Inuviscolide (IV), Telekin (V), Isotelekin (VI), 4 (15)-ß-Epoxyisotelekin (VII), Carabrone (VIII), Carabrol (IX), and 3- Deuteriomethyl-5-methyl-2,3-dihydrobenzofuran (X). CONCLUSION: Compounds I, III, IV,VII, VII and X are isolated from this plant for the first time.