Jiaqing Cao

Steroidal glycosides from the roots of Cynanchum amplexicaule Sieb. et Zucc.

Seven new steroidal glycosides (amplexicosides A (4), B (7), C (8), D (9), E (10), F (11), and G (12)), along with six known compounds (cynatratoside A (1), tylophoside A (2), cynatratoside B (3), glaucogenin A (5), glaucoside A (6), and hancoside A (13)) were isolated from the 95% ethanol extract of the roots of Cynanchum amplexicaule (Sieb. et Zucc.). Their structures were determined based on spectral and chemical evidence. Compound 12 has a 14, 15-secopregnane-type skeleton aglycone, which has not been reported in literature.

New dammarane-type triterpenoids from the leaves of Panax notoginseng and their protein tyrosine phosphatase 1B inhibitory activity

Background Panax notoginseng has been used as a general tonic agent to invigorate human body for millennia in China and continued to be used until present. Methods Some chromatographic methods were performed to isolate pure triterpenoids, and their structures were determined by nuclear magnetic resonance (NMR) experiments. Anti-diabetes activities of isolated compounds were evaluated through their inhibitory activity of protein tyrosine phosphatase 1B (PTP1B) enzyme. Results and Conclusion Three new dammarane-type triterpenoids, notoginsenoside-LX (1), notoginsenoside-LY (2), and notoginsenoside-FZ (3) together with eighteen known compounds were isolated from the Panax notoginseng leaves. The structure-activity relationship of the compounds with dammarane-type triterpenoids and their PTP1B inhibitory activity were also reported. Results showed that compounds 2, 15, 20, and 21 can significantly inhibit the enzyme activity of PTP1B in a dose-dependent manner, with inhibitory concentration 50 (IC50) values of 29.08 μM, 21.27 μM, 28.12 μM, and 26.59 μM, respectively. The results suggested that Panax notoginseng leaves might have potential as a new therapeutic agent for the treatment of diabetes.

New compounds from acid hydrolyzed products of the fruits of Momordica charantia L. and their inhibitory activity against protein tyrosine phosphatas 1B.

Four new cucurbitane-type triterpene sapogenins, compounds 1-4, together with other eight known compounds were isolated from the acid-hydrolyzed fruits extract of Momordica charantia L. Their chemical structures were established by NMR, mass spectrometry and X-ray crystallography. Compounds 1-7 and 9-12 were evaluated for their inhibitory activities toward protein tyrosine phosphatase 1B (PTP1B), a tyrosine phosphatase that has been implicated as a key target for therapy against type II diabetes. Compounds 1, 2, 4, 7 and 9 were shown inhibitory activities of 77%, 62%, 62% 60% and 68% against PTP1B, respectively. All of these tested compounds were exhibited higher PTP1B inhibition activities than that of the Na3VO4, a known PTP1B inhibitor used as positive control in present study. Structure activity relationship (SAR) analysis indicated that the inhibition activity of PTP1B was associated with the presence and number of -OH groups.

Novel dammarane-type triterpenes isolated from hydrolyzate of total Gynostemma pentaphyllum saponins

In this study, five novel triterpenes were isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum and identified as gypensapogenin H (1), gypensapogenin I (2), gypensapogenin L (3), gypensapogenin J (4) and gypensapogenin K (5), three of which (1-3) possess unprecedented ring A. All the isolated compounds were evaluated for cytotoxic activities in five cell lines and all the tested compounds showed significant anti-cancer activities against a series of human cancer cell lines, while having much weaker effect on the growth of normal cell. Among them, compound 1 showed strong inhibition toward MCF-7 human breast cancer cells (IC50 values 6.85 μM). Further mechanistic study demonstrated that compound 1 significantly induced MCF-7 cell apoptosis. Our results indicated that compound 1 may be a promising lead agent for further study.

Two new compounds from Carthamus tinctorius

From the dried petals of Carthamus tinctorius, a new flavonoid, (2R)-4′,5-dihydroxyl-6,7-di-O-β-d-glucopyranosyl flavanone (1) and a new aromatic glucoside, methyl-3-(4-O-β-d-glucopyranosylphenyl) propionate (4) were isolated along with four known compounds (2S)-4′,5-dihydroxyl-6,7-di-O-β-d-glucopyranosyl flavanone (2), 6-hydroxykaempferol-3,6-di-O-β-d-glucopyranoside (3), 4-O-β-d-glucosyl-trans-p-coumaric acid (5), and 4-O-β-d-glucosyl-cis-p-coumaric acid (6). Their structures were identified on the basis of chemical and spectroscopic methods.

New cytotoxic compounds from flowers of Lawsonia inermis L.

Three new compounds, a bicoumarin A (1), a biflavonoid A (2), and a biquinone A (3), as well as 12 other known compounds, were isolated from the flower of Lawsonia inermis L. The structures were elucidated by spectral analysis and new compounds 2 and 3 then were further confirmed by ECD calculations and single-crystal X-ray diffraction crystallography respectively. The cytotoxicity of the compounds against four cancer cell lines, including MCF-7, Hela, HCT-116, and HT-29 were evaluated using MTT assay. The IC50 values of compounds 3 and 5 against MCF-7, Hela, HCT-116, and HT-29 were 2.24, 1.42, 24.29, and 7.02 μM and 6.1, 2.44, 5.58, and 10.21 μM respectively. The two compounds exhibited stronger inhibitory activities than the positive control 5-fluorouracil (IC50=7.34, 11.50, 36.17, 18.83 μM) against the four tested cell lines. These results demonstrated that compounds from the flowers of L. inermis L. showed cytotoxic activity on MCF-7, Hela, HCT-116, and HT-29 cell lines.

Protein tyrosine phosphatase 1B inhibitory effect by dammarane-type triterpenes from hydrolyzate of total Gynostemma pentaphyllum saponins

Protein tyrosine phosphatase 1B (PTP1B) is an important factor in non-insulin-dependent diabetes mellitus (type-2 diabetes), and a promising target for treatment of diabetes and obesity. Therefore, the aim of this study is to investigate the inhibitory activities of constituents (three new together with twelve known triterpenes compounds) isolated from the hydrolyzate of total saponins from Gynostemma pentaphyllum. Their structures were accomplished mainly base on the spectroscopic methods, and then were further confirmed by X-ray crystal diffraction. All the compounds were evaluated for inhibitory activity against PTP1B. Current data suggested that the compounds 1, 3, 12, 13 and 14 were considered to be potential as antidiabetic agents, in which they could significantly inhibit the PTP1B enzyme activity in a dose-dependent manner.

Triterpenoid saponins from Gynostemma pentaphyllum.

Four new dammarane-type triterpene saponins, 1–4, were isolated from the aerial parts of Gynostemma pentaphyllum (Thunb.) Makino. Their structural elucidations were accomplished mainly on the basis of spectroscopic methods, such as IR, HR-TOF-MS, and NMR. Compounds 1–4 showed moderate cytotoxic activities against cancer cell lines HL-60, Colon205, and Du145 in vitro.

Depside derivatives with anti-hepatic fibrosis and anti-diabetic activities from Impatiens balsamina L. flowers.

Eighteen compounds (1-18), seven new (3-9) and eleven previously reported (1, 2, and 10-18), were isolated from the flowers of Impatiens balsamina (Linn). The structures of the isolated compounds were elucidated using different spectroscopic methods, including NMR (1D and 2D), UV, IR, and HR-ESI-MS. Analysis of the bioassay results showed the compounds had notable anti-hepatic fibrosis activity against murine Hepatic Stellate Cells (t-HSC/Cl-6) and anti-diabetics activity against α-glucosidase. Specifically, new compounds 7, 8, 9 showed significant inhibitory activity on t-HSC/Cl-6 cells with IC50 values of 42.12, 109.2, and 34.04 μg/mL respectively, while the IC50 values of positive control Silymarin and Fufang Biejia Ruangan Pian were 202.34 and 231.56 μg/mL, respectively. In addition, compounds 2, 4, 7, 8, 10, 11, 17, and 18 exhibited excellent α-glucosidase inhibitory activity. Among these compounds, 7 exhibited the highest activity with an IC50 value of 0.72 μg/mL, while the IC50 value of the positive control acarbose was 3.36 μg/mL. This is the first study evaluating the anti-hepatic fibrosis and anti-diabetic activities of compounds isolated from the flowers of I. balsamina.

25-Methoxylprotopanaxadiol derivatives and their anti-proliferative activities.

(20R)-25-Methoxyl-dammarane-3β,12β,20-triol (25-OCH₃-PPD) is a dammarane-type sapogenin showing anti-proliferative potential. In our study, two series of analogs substituted at the C-3 or C-3 and C-12 positions with fatty acids were prepared conveniently. The cytotoxic activity of these compounds was evaluated using four different human tumor cell lines (A549, Hela, HT-29 and MCF-7) and a normal cell line (IOSE144). As compared with 25-OCH₃-PPD, compounds 1a, 1b, 2a and 2b showed better anti-proliferative activities against all tumor cell lines and all the derivatives, with low toxicities in the normal cell line. Compound 1a (C-3 monoformiate) exhibited the strongest activity with the IC₅₀ value of 5.2 μM towards HT29 cells. The results indicated that the difference in the substituents may affect the anti-proliferative activity of the compounds. The longer the side chain of 25-OCH₃-PPD is, the lower the anti-proliferative activity would be. This information may be useful for evaluating the structure-activity relationship of other dammarane-type sapogenins and for development of novel antineoplastic agents.