Fu-Shuang Li

Anticancer potential of Hericium erinaceus extracts against human gastrointestinal cancers

ETHNOPHARMACOLOGICAL RELEVANCE Hericium is a genus of mushrooms (fungus) in the Hericiaceae family. Hericium erinaceus (HE) has been used for the treatment of digestive diseases for over 2000 years in China. HE possesses many beneficial functions such as anticancer, antiulcer, antiinflammation and antimicrobial effects, immunomodulation and other activities. The aim of the studies was to evaluate the anticancer efficacy of two extracts (HTJ5 and HTJ5A) from the culture broth of HE against three gastrointestinal cancers such as liver, colorectal and gastric cancers in both of in vitro of cancer cell lines and in vivo of tumor xenografts and discover the active compounds. MATERIALS AND METHODS Two HE extracts (HTJ5 and HTJ5A) were used for the studies. For the study of chemical constituents, the HTJ5 and HTJ5A were separated using a combination of macroporous resin with silica gel, HW-40 and LH-20 chromatography then purified by semipreparative high-performance liquid chromatography (HPLC) and determined by nuclear magnetic resonance (NMR) spectra. For the in vitro cytotoxicity studies, HepG2 and Huh-7 liver, HT-29 colon, and NCI-87 gastric cancer cell lines were used and MTT assay was performed to determine the in vitro cytotoxicity. For in vivo antitumor efficacy and toxicity studies, tumor xenograft models of SCID mice bearing liver cancer HepG2 and Huh-7, colon cancer HT-29 and gastric cancer NCI-87 subcutaneously were used and the mice were treated with the vehicle control, HTJ5 and HTJ5A orally (500 and 1000 mg/kg/day) and compared to 5-fluorouraci (5-FU) at the maximum tolerated dose (MTD, 25-30 mg/kg/day) intraperitoneally daily for 5 days when the tumors reached about 180-200 mg (mm(3)). Tumor volumes and body weight were measured daily during the first 10 days and 2-3 times a week thereafter to assess the tumor growth inhibition, tumor doubling time, partial and complete tumor response and toxicity. RESULTS Twenty-two compounds were obtained from the fractions of HTJ5/HTJ5A including seven cycli dipeptides, five indole, pyrimidines, amino acids and derivative, three flavones, one anthraquinone, and six small aromatic compounds. HTJ5 and HTJ5A exhibited concentration-dependent cytotoxicity in vitro against liver cancer HepG2 and Huh-7, colon cancer HT-29, and gastric cancer NCI-87 cells with the IC50 in 2.50±0.25 and 2.00±0.25, 0.80±0.08 and 1.50±0.28, 1.25±0.06 and 1.25±0.05, and 5.00±0.22 and 4.50±0.14 mg/ml; respectively. For in vivo tumor xenograft studies, HTJ5 and HTJ5A showed significantly antitumor efficacy against all four xenograft models of HepG2, Huh-7, HT-29 and NCI-87 without toxicity to the host. Furthermore, HTJ5 and HTJ5A are more effective than that of 5-FU against the four tumors with less toxicity. CONCLUSION HE extracts (HTJ5 and HTJ5A) are active against liver cancer HepG2 and Huh-7, colon cancer HT-29 and gastric cancer NCI-87 cells in vitro and tumor xenografts bearing in SCID mice in vivo. They are more effective and less toxic compared to 5-FU in all four in vivo tumor models. The compounds have the potential for development into anticancer agents for the treatment of gastrointestinal cancer used alone and/or in combination with clinical used chemotherapeutic drugs. However, further studies are required to find out the active chemical constituents and understand the mechanism of action associated with the super in vivo anticancer efficacy. In addition, future studies are needed to confirm our preliminary results of in vivo synergistic antitumor efficacy in animal models of tumor xenografts with the combination of HE extracts and clinical used anticancer drugs such as 5-FU, cisplatin and doxurubicin for the treatment of gastrointestinal cancers.

Two new selaginellin derivatives from Selaginella tamariscina (Beauv.) Spring

Two new selaginellin derivatives, selaginellins K (1) and L (2), were isolated from Selaginella tamariscina (Beauv.) Spring and characterized as 2-formyl-4,4′-dihydroxy-3-[(4-hydroxyphenyl)ethynyl]biphene and 4,4′-dihydroxy-2-methyl-3-[(4-hydroxyphenyl)ethynyl]biphene on the basis of their spectroscopic data including UV, IR, 1D, and 2D NMR as well as HR-ESI-MS spectroscopic analysis.

Selaginellin C, a new natural pigment from Selaginella pulvinata Maxim (Hook et Grev.)

A novel compound, selaginellin C (1), was isolated from Selaginella pulvinata Maxim (Hook et Grev.) as (R,S)-4-((1,2-dihydroxyethyl)-2′,4′-dihydroxy-3-((4-hydroxyphenyl)ethynyl)biphenyl-2-yl)((4-hydroxyphenyl)methylene)cyclohexa-2,5-dienone, along with two known compounds, selaginellin (2) and selaginellin A (3). The structure of the new compound was elucidated on the basis of 1D and 2D NMR as well as HR-ESI-MS spectroscopic analysis.

Selaginellins I and J, two new alkynyl phenols, from Selaginella tamariscina (Beauv.) Spring

Selaginellins I (1) and J (2), two new compounds, were isolated from Selaginella tamariscina (Beauv.) Spring and were characterized as (R,S)-4-((2′,4′-dihydroxy-4-(hydroxymethyl)-3-((4-hydroxyphenyl)ethynyl)biphenyl-2-yl)(4-hydroxyphenyl)methylene)cyclohexa-2,5-dienone (1) and (R,S)-4-((3-((3,4-dihydroxyphenyl)ethynyl)-4′-hydroxy-4-(hydroxymethyl)biphenyl-2-yl)(4-hydroxyphenyl)methylene)cyclohexa-2,5-dienone (2) on the basis of UV, IR, 1D and 2D NMR, and HR-ESI-MS spectroscopic analysis.

Selaginellin M, a new selaginellin derivative from Selaginella pulvinata

A new selaginellin derivative, selaginellin M (1), together with one known compound, selaginellin E (2), was isolated from Selaginella pulvinata. The structure of the new compound was elucidated and named as (R,S)-4-((4′-hydroxy-4-((2-hydroxyethoxy)methyl))-3-((4-hydroxyphenyl)ethynyl)biphenyl-2-yl)(4-hydroxyphenyl)methylene)cyclohexa-2,5-dienone on the basis of the spectroscopic data including UV, IR, 1D, and 2D NMR as well as HR-ESI-MS analysis.

Unciflavones A–F, six novel flavonoids from Selaginella uncinata (Desv.) Spring

Six new flavonoids, unciflavones A-F (1-6), have been isolated from medicinal plant Selaginella uncinata (Desv.) Spring. Their structures were established on the basis of extensive NMR analysis including 1D NMR ((1)H, (13)C and DEPT) and 2D NMR (COSY, HSQC, HMBC) experiments as well as HRESIMS analysis. All compounds possess exceptional structural features with an aryl substituent at the C-8 position, which are uncommonly encountered in natural resources and firstly reported in genus Selaginella.

Uncinataflavone, a new flavonoid with a methyl benzoate substituent from Selaginella uncinata

Uncinataflavone (1), a new flavonoid, together with four known compounds (2–5), was isolated from Selaginella uncinata (Desv.) Spring. Compounds 2 and 3 were isolated from the genus selaginella for the first time. The structure of the new compound was determined as methyl 3-(5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-6-yl)-4-methoxybenzoate by means of spectroscopic evidence, including UV, IR, 1D and 2D NMR analyses as well as HR-ESI-MS. These compounds (1–5) were evaluated for the antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl assay system.

A new flavonoid with 6-phenyl substituent from Selaginella uncinata

A new flavonoid, 6-(5-acetyl-2-methoxyphenyl)-apigenin (1), together with nine known compounds (2–10), was isolated from Selaginella uncinata (Desv.) Spring. This is the first report of the spectroscopic data of compound 3. Compound 2 was first reported from this species. The structure of the new compound was elucidated on the basis of spectroscopic evidence, including 1D and 2D NMR as well as HR-EI-MS analysis.

Anthraquinones and biflavonoids from Selaginella delicatula

0009-3130/11/4704-0627 2011 Springer Science+Business Media, Inc. Department of Medicinal Chemistry, Central South University, Changsha 410013, P. R. China, fax: +86 731 82650386, e-mail: tgs395@yahoo.com.cn. Published in Khimiya Prirodnykh Soedinenii, No. 4, pp. 553–554, July–August, 2011. Original article submitted November 15, 2009. Chemistry of Natural Compounds, Vol. 47, No. 4, September, 2011 [Russian original No. 4, July–August, 2011]

A new flavonol from Sophora tonkinensis

A new flavonol, tonkinensisol, was isolated from the roots of Sophora tonkinensis, together with three known compounds named as bayin, vitexin and lupeol. Their structures were elucidated on the basis of spectroscopic evidence. Additionally, tonkinensisol showed moderate cytotoxicity suppressing the proliferation of HL-60 cells in vitro.