Daonian Zhou

Anti-tumor and anti-angiogenic effects of Macrothelypteris viridifrons and its constituents by HPLC–DAD/MS analysis

ETHNOPHARMACOLOGICAL RELEVANCE Macrothelypteris viridifrons is widely distributed in south of China and has been used as folk medicine to treat cancer, hydropsy, and traumatic bleeding. AIM OF THE STUDY To investigate the chemical constituents and the anti-tumor and anti-angiogenic effects of Macrothelypteris viridifrons. MATERIALS AND METHODS An HPLC-DAD/MS technique was used to determine the flavonoid profile of Macrothelypteris viridifrons. The anti-tumor effect of Macrothelypteris viridifrons was evaluated by in vivo mice bearing H22 hepatoma cells transplantation tumor model. And the anti-angiogenic activity was investigated by measuring the effects on the in vitro proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). Furthermore, the in vivo zebrafish model was applied to evaluate the anti-angiogenic effect of Macrothelypteris viridifrons. RESULTS 18 flavonoids were identified from Macrothelypteris viridifrons. Administration of Macrothelypteris viridifrons significantly inhibited the tumor growth and the expression of vascular endothelial growth factor (VEGF) and CD34. Meanwhile, Macrothelypteris viridifrons showed significant inhibition on proliferation, migration and tube formation of HUVECs in vitro and the intersegmental vessels formation in zebrafish model. CONCLUSIONS Macrothelypteris viridifrons showed significant anti-tumor and anti-angiogenic effects and might be developed as a novel anti-tumor drug.

Chemical constituents of radix Ranunculus ternati.

3β-Acetoxy-(20S, 22E)-dammaran-22-en-25-ol, a new triterpene, was isolated along with five known triterpenes (ursolic acid, oleanolic acid, betulinic acid, 3-epiocotillol acetate, and dimmarenediol II acetate), and α-D-glc and sucrose from Radix Ranunculus ternati All of them, except oleanolic acid and α-D-glc, were isolated from the family of Ranunculaceae for the very first time, and the NMR data of sucrose was first described. In addition, the absolute configurations of α-D-glc and the glucose component of sucrose were determined.

A new flavonoid from Macrothelypteris torresiana

A new flavonoid, 5,7-dihydroxy-2-(1-hydroxy-2,6-dimethoxy-4-oxo-cyclohex)-chromen-4-one (1), was isolated from the roots of Macrothelypteris torresiana (Gaud.) Ching. (Thelypteridaceae). The structure of the product was identified on the basis of detailed spectral analysis, including X-ray structure analysis.

Flavonoids from the aerial parts of Macrothelypteris torresiana.

Two new flavone derivatives (1 and 2) were isolated from the aerial parts of Macrothelypteris torresiana, along with four known flavonoids: protoapigenin, apigenin, kaempferol and quercetin. The structures were determined on the basis of spectroscopic data. Compound 1 showed weak cytotoxic activity against human tumour cell lines HepG2, MCF7 and K562.

DICO, a novel nonaromatic B-ring flavonoid, induces G2/M cell cycle arrest and apoptosis in human hepatoma cells.

DICO was a novel nonaromatic B-ring flavonoid obtained from Macrothelypteris torresiana. In the present work, we investigated the antitumor activity and the antineoplastic mechanism of DICO. Our study showed that DICO inhibited the growth of HepG2 cells in dose and time-dependent manners. As well as DICO induced G2/M cell cycle arrest and apoptosis via a ROS-mediated mitochondrial pathway. Western blot assay demonstrated that DICO decreased Bcl-2 level and induced Bax translocation to cause cytochrome c release. Subsequently, caspase-9 and caspase-3 were activated. Meanwhile, the alterations of cyclin A and B1, p-CDK1 and p-cdc25c levels were also observed in response to DICO treatment. Taken together, DICO displayed a significant antitumor effect through G2/M cell cycle arrest and apoptosis induction, which suggested DICO might have therapeutic potential against tumors.

Parathelypteriside attenuates cognition deficits in d-galactose treated mice by increasing antioxidant capacity and improving long-term potentiation

Parathelypteriside (PG), a stilbenoid compound, was extracted from Parathelypteris glanduligera (kze.) ching that exhibits antioxidative and anti-inflammatory effects. The aim of this study was to investigate the protective effect of PG against the d-galactose (d-gal)-induced neurotoxicity in mice. It was found that long-term intraperitoneal (i.p.) injection of PG (5 or 10 mg/(kg day)) for two weeks significantly improved the behavioral performance of d-gal-treated mice in both Morris water maze test and step-down avoidance test. Biochemical examination revealed that PG reduced the increased levels of malondialdehyde (MDA), and attenuated the decreased activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase in the hippocampus of d-gal-treated mice. Furthermore, the electrophysiological assay showed that PG significantly rescued the long-term potentiation (LTP) impairment in mice hippocampus, and western blotting analysis indicated that the effects of PG on LTP might be attributed to the activation of cAMP-response element-binding protein (CREB). Together, these results suggested that the natural product PG represented a potential source of medicine for the treatment of the neurodegenerative diseases.

Three new polyphenols from the rhizomes of Arachniodes exilis

Three new polyphenols, araspidin BB (1), arachniodesin A (2) and arachniodesin B (3), together with two known compounds, epicatechin (4) and procyanidin B-2 (5), were isolated from the rhizomes of Arachniodes exilis. The structures of three new compounds were elucidated as 5-methyl-methylene-bis-phlorobutyrophenone (1), 4β-ethoxycarbonylmethylepicatechin (2) and epicatechin-(4β → 8)-4β-ethoxycarbonylmethylepicatechin (3), on the basis of their spectral analysis and by comparing them with the related model compounds. Compounds 4 and 5 were obtained from the title plant for the first time.

Determination of protoapigenone in rat plasma by high-performance liquid chromatography with UV detection and its application in pharmacokinetic studies.

A simple and sensitive HPLC method using UV detection was developed to determine the concentration of protoapigenone in rat plasma. Chromatographic separation was conducted on a C18 column with a mobile phase consisting of an acetonitrile-methanol-aqueous phase (containing 0.2% acetic acid, pH 3.0) system at a flow rate of 1.0 mL/min. The UV detector was set at 248 nm. The calibration curve was linear over the range of 0.031-10.0 µg/mL. The lower limit of quantification was 31 ng/mL. The recoveries for plasma samples ranged from 70.3 to 82.5%. The intra- and inter-day accuracy and precision fulfilled the international standards. This method was successfully applied to a pharmacokinetic study of protoapigenone in rats after oral administration of protoapigenone. It was shown that protoapigenone could be absorbed rapidly after oral administration and could reach the maximum concentration within 1 h.