Pararorine A, isoindolinone alkaloid from the endophytic fungus Paramyrothecium roridum and its anti-tumor activity.

Pararorine A, a new isoindolinone alkaloid was isolated from Paramyrothecium roridum, an endophytic fungus from the medicinal plant Gynochthodes officinalis (F.C. How) Razafim. & B. Bremer. The structure of this compound was elucidated by extensive spectroscopic (UV, IR, MS, and NMR) analyses. In addition, the antitumor activity of pararorine A was evaluated against SF-268, MCF-7, HepG2, and A549 tumor cell lines. The results revealed that pararorine A exhibited potent antitumor activities with the IC50 values ranging from 1.69 to 8.95 µM. Moreover, the tumor cell inhibitory activity of pararorine A was evidenced by promoting cytochrome C release and cell cycle arrest as well as the induction of apoptosis by the up-regulation of the protein expressions of JNK and Bax through PARP-cleavage and caspase 3-cleavage.

Irpexols A-C, xanthone derivatives from the endophyte fungus Irpex laceratus A878.

Three new xanthone derivatives irpexols A-C (1-3) and five known xanthones including three dimeric ones were successfully isolated from Irpex laceratus A878, an endophytic fungus of the family Irpicaceae from the medicinal plant Pogostemon cablin (Blanco) Bentham (Lamiaceae). The structures of these compounds were elucidated by extensive spectroscopic analyses including ultraviolet-visible spectroscopy (UV), infrared spectroscopy (IR), mass spectrometry (MS), and nuclear magnetic resonance (NMR). All of the three new compounds (1-3) share a de-aromatic and highly­oxygenated xanthone skeleton. In addition, the cytotoxic activity of compounds 1-8 were evaluated against SF-268, MCF-7, HepG2, and A549 tumor cell lines. The results revealed that compound 6 showed moderate cytotoxic activity with the IC50 values ranging from 24.83 to 45.46 µM, while the IC50 values of the positive control adriamycin was ranging from 1.11 to 1.44 µM.

3-Carboxy-indole derivatives from the deep-sea-derived fungus Phomopsis tersa FS441.

Three new compounds phomtersines A-C (1-3) together with nine known compounds were isolated from the marine-derived fungus Phomopsis tersa FS441. Their structures were sufficiently established by spectroscopic methods, including extensive 1D and 2D NMR techniques and modified Snatzke's method. Moreover, compounds 1-12 were evaluated for cytotoxic and anti-inflammatory activities. As a result, phomtersine B (2) and the known compound 10 showed moderate cytotoxic activity against the four tested cell lines with IC50 values ranging from 20.21 to 36.53 µM, and phomtersine A (1) exhibited moderate inhibitory activity against LPS-induced NO production.

Cytospotones A-D, four new polyketones from the endophytic fungus Cytospora sp. A879.

Three new α-pyrone derivatives cytospotones A-C (1-3) and a new cyclohexenone derivative cytospotone D (4) together with four known α-pyrones were isolated from the endophytic fungus Cytospora sp. A879 of Pogostemon cablin (Blanco) Benth. The structures of 1-4 were elucidated primarily by spectroscopic methods (1D, 2D NMR and HRESIMS), ECD spectra analyses, and ECD calculations. Furthermore, the four new compounds (1-4) were evaluated for their anti-inflammatory and α-glucosidase inhibitory activities. The results showed that compound 1 had moderate inhibitory effect on LPS-induced NO production in RAW 264.7 macrophages.

Cytospones E-J from the endophytic fungus Cytospora rhizophorae.

Cytospones E-J (1-6), six unreported α-pyrone derivatives, together with six known ones (7-12) were isolated from the solid culture of the endophytic fungus Cytospora rhizophorae A761, an endophytic fungus from Gynochthodes officinalis. The structures of the unreported compounds were unambiguously elucidated through spectroscopic analyses (1D, 2D NMR and HRESIMS), and their absolute configurations were assigned by single-crystal X-ray diffraction (Cu Kα) analyses. Furthermore, cytospones E-J were evaluated for anti-inflammatory and α-glucosidase inhibitory activities.

Cytotoxic diaporindene and tenellone derivatives from the fungus Phomopsis lithocarpus.

Nine new compounds, including five natural rarely-occurring 2, 3-dihydro-1H-indene derivatives named diaporindenes E-I (1-5), and four new benzophenone analogues named tenellones J-M (6-9) were isolated from the deep-sea sediment-derived fungus Phomopsis lithocarpus FS508. All the structures for these new compounds were fully characterized on the basis of spectroscopic data, NMR spectra, and ECD calculation and single-crystal X-ray diffraction analysis. The potential anti-tumor activities of compounds 1-9 against four tumor cell lines SF-268, MCF-7, HepG-2, and A549 were evaluated using the SRB method. Compound 7 exhibited cytotoxic activity against the SF-268 cell line with an IC50 value of 11.36 µmol·L-1.

Asperorydines N-P, three new cyclopiazonic acid alkaloids from the marine-derived fungus Aspergillus flavus SCSIO F025.

Three new tricyclic cyclopiazonic acid (CPA) related alkaloids asperorydines N-P (1-3), together with six known compounds (4-9) were isolated and characterized from the fungus Aspergillus flavus SCSIO F025 derived from the deep-sea sediments of South China Sea. The structures including absolute configurations of 1-3 were deduced from spectroscopic data, X-ray diffraction analysis, and electronic circular dichroism (ECD). All compounds were evaluated for the antioxidative activities against DPPH, cytotoxic activities against four tumor cell lines (SF-268, HepG-2, MCF-7, and A549), and antimicrobial activities. Compound 9 showed significant radical scavenging activities against DPPH with an IC50 value of 62.23 µM and broad-spectrum cytotoxicities against four tumor cell lines with IC50 values ranging from 24.38 to 48.28 µM. Furthermore, compounds 4-9 exhibited weak antimicrobial activities against E scherichia coli, and compound 9 also showed antibacterial activity against Bacillus thuringiensis, Micrococcus lutea, Staphylococcus aureus, Bacillus subtilis, Methicillin resistant Staphylococcus aureus.

Salicylaldehyde derivatives from a marine-derived fungus Eurotium sp. SCSIO F452.

Two pairs of new salicylaldehyde derivative enantiomers, salicylaldehydiums A and B (1 and 2), along with five known analogues were isolated and identified from a marine-derived fungus Eurotium sp. SCSIO F452. Their structures and absolute configuration were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. All the new optical pure enantiomers [(+)-1, (-)-1, (+)-2, (-)-2] were evaluated for their cytotoxic and antioxidative activities. Compound (-)-1 exhibited weak cytotoxic activity.

Trichothecene macrolides from the endophytic fungus Paramyrothecium roridum and their cytotoxic activity.

The chemical investigation of the secondary metabolites of Paramyrothecium roridum (homotypic synonym: Myrothecium roridum), an endophytic fungus isolated from the medicinal plant Morinda officinalis, led to the isolation of twelve cytotoxic trichothecene macrolides, including two new ones, named myrothecines H and I. The structures of the new macrolides were elucidated by extensive spectroscopic measurements analyses. In addition, the cytotoxic activities of these compounds were evaluated against SF-268, NCI-H460, and HepG-2 tumor cell lines, and all isolated compounds (1-12) exhibited significant cytotoxic activity with the IC50 ranging from 0.0002-16.2 µM. Moreover, the inhibitory activity of myrothecines H and I was evidenced by inducing phosphorylation of JNK (c-Jun N-terminal protein kinase) protein and the PARP (poly ADP-ribose polymerase) cleavage, and eventually induce apoptosis of HepG-2 cells. The results indicated that myrothecines H and I could be applied as chemotherapeutic agents.

Four new metabolites from the endophytic fungus Diaporthe lithocarpus A740.

One new benzophenone derivative, named tenllone I (1), two new eremophilane derivatives lithocarins B (2) and C (3), and a new monoterpentoid lithocarin D (4), together with two know compounds (5 and 6) were isolated from the endophytic fungus Diaporthe lithocarpus A740. All of the structures for these new compounds were fully characterized and established on the basis of extensive spectroscopic interpretation. In addition, all the isolated compounds were evaluated in vitro for their cytotoxic activity. Compounds 2, 3, and 5 showed weak inhibitory activities against tumor cell lines.

Two new metabolites from Daldinia eschscholtzii, an endophytic fungus derived from Pogostemon cablin.

The chemical investigation of the mycelia of endophytic fungus Daldinia eschscholtzii A630, which was isolated from the medicinal plant Pogostemon cablin, resulted in the isolation of two new compounds, named eschscholin A (1), 3-ene-2-methyl-2H-1-benzopyran-5-ol (2), and one new natural product 3,5-dihydroxy-2-methyl-4H-chromen-4-one (3), along with seven known compounds. Their structures were fully characterized by means of detailed spectroscopic analysis, and in comparison with published data for known compounds. All of the isolated compounds (1-10) were evaluated for their antibacterial activities.

Cerrenins A-C, cerapicane and isohirsutane sesquiterpenoids from the endophytic fungus Cerrena sp.

One new cerapicane cerrenin A (1), and two new isohirsutane sesquiterpenoids cerrenins B and C (2 and 3), were isolated from the broth extract of Cerrena sp. A593. Cerrenin A featured a rare cage-like bicyclo[3.2.1]octane skeleton, and cerrenin B represented the rearranged triquinane-type sesquiterpenoid. Their structures were extensively elucidated by NMR spectroscopic analysis with the absolute configuration determined by X-ray crystallography and ECD calculations. The anti-cancer activity for all the compounds were evaluated, and their plausible biosynthetic relationships involving fascinating carbon skeleton rearrangements were also suggested.

[Sesquiterpenoids of endophytic fungus Cerrena sp. from Pogostemon cablin and their cytotoxic activities].

The secondary metabolites of endophytic fungus Cerrena sp.A593 from Pogostemon cablin and their cytotoxic activities were investigated. Eight sesquiterpenoids were isolated from the fermentation broth of the strain A593 by silica gel, reverse phase silica gel, Sephadex LH-20, HPLC and so on. Their structures were identified as chloriolin B(1), chloriolin C(2), pleurocybellone A(3), dihydrohypnophilin(4), cucumin F(5), antrodin A(6), 10α-hydroxyamorphan-4-en-3-one(7), and connatusin A(8). Compounds 1- 8 were firstly found from the genus Cerrena. All isolated sesquiterpenoids were evaluated for in vitro cytotoxic activities against HepG-2, SF-268, MCF-7 and NCI-H460 tumor cell lines. Compounds 1-3 showed inhibitory activities against the four tumor cell lines with IC50 values ranging from 20.33 to 63.13 µmol•L⁻¹.

Influence of autologous blood transfusion in liver transplantation in patients with hepatitis B on the function and hemorheology of red blood cells.

The present study aimed to characterize the function and hemorheology of red blood cells (RBCs) recovered during liver transplantation surgery in patients with hepatitis B and decompensation. A total of 15 hepatitis B patients with decompensation who underwent liver transplantation surgery were included in the present study. Blood samples were recovered during the liver transplantation surgery using an Autologous Blood Recovery System. The morphology and structure of RBCs were characterized and compared between pre-operative and recovered blood samples. In addition, the physiological functions of RBCs were measured and compared between pre-operative and recovered blood samples. No significant differences in the morphological score, 2,3-diphosphoglycerate, Na+K+-ATPase, Ca2+-ATPase, Mg2+-ATPase, malondialdehyde and osmotic fragility were identified between RBCs in the pre-operative and recovered blood samples. The level of free hemoglobin in RBCs of the recovered blood samples was significantly higher than in the pre-operative blood samples (P<0.05). Medium- and high-shear blood viscosities in the recovered blood samples were significantly lower than those observed in the pre-operative blood samples (P<0.05). Casson viscosity in the recovered blood samples was significantly higher compared with the pre-operative blood samples. However, no significant differences (P>0.05) in the low-shear blood viscosity, plasma viscosity, relative blood viscosity, erythrocyte aggregation index or Casson yield stress were identified between recovered and pre-operative blood samples. These findings suggested that autologous blood transfusion in liver transplantation surgery in patients with hepatitis B and decompensation had no significant influence on the morphology, structure, function and hemorheology of RBCs.

Two New Metabolites from the Endophytic Fungus Alternaria sp. A744 Derived from Morinda officinalis.

Two new compounds isobenzofuranone A (1) and indandione B (2), together with eleven known compounds (3-13) were isolated from liquid cultures of an endophytic fungus Alternaria sp., which was obtained from the medicinal plant Morinda officinalis. Among them, the indandione (2) showed a rarely occurring indanone skeleton in natural products. Their structures were elucidated mainly on the basis of extensive spectroscopic data analysis. All of the compounds were evaluated with cytotoxic and α-glucosidase inhibitory activity assays. Compounds 11 and 12 showed significant inhibitory activities against four tumor cell lines; MCF-7, HepG-2, NCI-H460 and SF-268, with IC50 values in the range of 1.91-9.67 µM, and compounds 4, 5, 9, 10, 12 and 13 showed excellent inhibitory activities against α-glucosidase with IC50 values in the range of 12.05-166.13 µM.

[Acupuncture mainly with "guoyanre" manipulation for amblyopia in children].

OBJECTIVE: To observe the effect difference between reinforcing-reducing manipulation and "guoyanre" manipulation for amblyopia in children. METHODS: A total of 68 children patients with amblyopia were assigned into an observation group and a control group by random number table, 34 cases (68 eyes) in each one. In the observation group, reinforcing-reducing manipulation was used at Yuyao (EX-HN 4), Taiyang (EX-HN 5), Tongziliao (GB 1), Jingming (BL 1), Cuanzhu (BL 2), and Chengqi (ST 1); twirling-reinforcing method was applied at Ganshu (BL 18), Shenshu (BL 23), and Guangming (GB 37);"guoyanre"manipulation was applied at bilateral Fengchi (GB 20). The acupoints and manipulations in the control group were the same as those in the observation group, except Fengchi (GB 20) with reinforcing-reducing method. All the treatment was given for 4 courses, 5 times as a course and once a day. The vision improvement was observed half a year after treatment. RESULTS: The effective rates for ametropic amblyopia in the observation and control groups were respectively 92.0% (23/25) and 70.4% (19/27); anisometropic amblyopia, 85.7% (18/21) and 55.0% (11/20); strabismic amblyopia, 66.7% (12/18) and 29.4% (5/17). The effect of each type in the observation group was better than that in the control group (all P<0.05). CONCLUSION: "Guoyanre"manipulation for amblyopia is superior to reinforcing-reducing method and can obviously improve the vision.

Three new highly-oxygenated metabolites from the endophytic fungus Cytospora rhizophorae A761.

Cytosporaphenones A-C, one new polyhydric benzophenone and two new naphtopyrone derivatives, along with eight known ones, were isolated from Cytospora rhizophorae, an endophytic fungus from Morinda officinalis. Their structures were fully characterized by means of detailed spectroscopic analysis and X-ray single crystal diffraction. To our knowledge, the three new compounds were the most highly oxygenated metabolites of their families discovered in nature. Moreover, all of the compounds were evaluated for in vitro cytotoxic activities against MCF-7, NCI-H460, HepG-2 and SF-268 tumor cell lines, and the new compound 1 exhibited weak growth inhibitory activity against the tumor cell lines MCF-7 and HepG-2 with IC50 values of 70 and 60µM, respectively.

Acylphloroglucinols from the leaves of Callistemon viminalis.

A phytochemical study on the leaves of Callistemon viminalis, a widely distributed ornamental and medicinal plant of agricultural importance in China, resulted in the isolation of eleven acylphloroglucinols, including six new ones named callistenones F-K (1-6), as well as five known congeners. Their structures were fully characterized using spectral data interpretation for the new structures and compared to published data for the known ones. All the isolated compounds were evaluated for in vitro antimicrobial activity and growth inhibitory activity against four tumor cell lines (MCF-7, NCI-H460, SF-268 and HepG-2).

Two Trichothecene Mycotoxins from Myrothecium roridum Induce Apoptosis of HepG-2 Cells via Caspase Activation and Disruption of Mitochondrial Membrane Potential.

Trichothecene mycotoxins are a type of sesquiterpenoid produced by various kinds of plantpathogenic fungi. In this study, two trichothecene toxins, namely, a novel cytotoxic epiroridin acid and a known trichothecene, mytoxin B, were isolated from the endophytic fungus Myrothecium roridum derived from the medicinal plant Pogostemon cablin. The two trichothecene mytoxins were confirmed to induce the apoptosis of HepG-2 cells by cytomorphology inspection, DNA fragmentation detection, and flow cytometry assay. The cytotoxic mechanisms of the two mycotoxins were investigated by quantitative real time polymerase chain reaction, western blot, and detection of mitochondrial membrane potential. The results showed that the two trichothecene mycotoxins induced the apoptosis of cancer cell HepG-2 via activation of caspase-9 and caspase-3, up-regulation of bax gene expression, down-regulation of bcl-2 gene expression, and disruption of the mitochondrial membrane potential of the HepG-2 cell. This study is the first to report on the cytotoxic mechanism of trichothecene mycotoxins from M. roridum. This study provides new clues for the development of attenuated trichothecene toxins in future treatment of liver cancer.

Two new xyloketals from the endophytic fungus Endomelanconiopsis endophytica derived from medicinal plant Ficus hirta.

Chemical examination of the liquid culture of Endomelanconiopsis endophytica A326 isolated from the Chinese folk medicine Ficus hirta resulted in the isolation of two new xyloketals named xyloketals K and L (1-2) and three known analogs (3-5) including a new natural product (5). Their structures were determined on the basis of extensive spectroscopic analysis. All compounds were evaluated for their cytotoxic activities against the SF-268, MCF-7, NCI-H460, and HepG-2 tumor cell lines. Nonetheless, no significant activity was observed.