Yin Nian

Cycloartane triterpenoids from Cimicifuga yunnanensis induce apoptosis of breast cancer cells (MCF7) via p53-dependent mitochondrial signaling pathway

The present study was carried out to investigate the antitumor activity of five cycloartane triterpenoids isolated from Cimicifuga yunnanensis on the breast cancer cell line MCF7 and its corresponding drug resistant subline R‐MCF7, including cimigenol‐3‐O‐β‐d‐xylopyranoside (compound 1), 25‐O‐acetylcimigenol‐3‐O‐β‐d‐xylopyranoside (compound 2), 25‐chlorodeoxycimigenol‐3‐O‐β‐d‐xylopyranoside (compound 3), 25‐O‐acetylcimigenol‐3‐O‐α‐l‐arabinopyranoside (compound 4) and 23‐O‐acetylcimigenol‐3‐O‐β‐d‐xylopyranoside (compound 5). The results showed that compounds 2–5 have relatively high antitumor activity on both MCF7 and R‐MCF7 cells. The involvement of apoptosis as a major cause of cycloartane triterpenoids‐induced cell death was further confirmed. The results of RT‐PCR showed that compounds 2–5 increased the expression of p53 and bax, which led to the loss of mitochondrial potential and then resulted in the activation of caspase‐7. These findings collectively demonstrated that compounds 2–5 induced apoptosis of MCF7 via p53‐dependent mitochondrial pathway. Copyright

Two New Classes of T-Type Calcium Channel Inhibitors with New Chemical Scaffolds from Ganoderma cochlear.

T-type calcium channel (TTCC) inhibitors hold great potential for the treatment of a variety of neurological disorders. Cochlearoids A-E (1-5), five pairs of dimeric meroterpenoid enantiomers, and cochlearines A (6) and B (7), two pairs of enantiomeric hybrid metabolites, were isolated and characterized from Ganoderma cochlear. Biological evaluation found that compounds (+)-1, (-)-3, and (±)-6 significantly inhibited Cav3.1 TTCC and showed noticeable selectivity against Cav1.2, Cav2.1, Cav2.2, and Kv11.1 (hERG) channels.

Triterpenes from the aerial parts of Cimicifuga yunnanensis and their antiproliferative effects on p53(N236S) mouse embryonic fibroblasts.

Nine new triterpene derivatives, yunnanterpenes A-F (1-6), 15,16-seco-cimiterpenes A and B (7, 8), and cimilactone C (9), and 15 known analogues (10-24) were isolated from the aerial parts of Cimicifuga yunnanensis. The new structures were established using a combination of MS, NMR, and single-crystal X-ray diffraction techniques. WT MEFs (wild-type mouse embryonic fibroblasts) and tumorigenic cell lines p53(-/-)+H-RasV12 and p53(-/-)+p53(N236S)+H-RasV12 were used for evaluating active structures, targeting p53(N236S) (corresponding to p53(N239S) in humans) mutation. Compound 5 showed nonselective activities against these cell lines, with IC50 values of 5.8, 8.6, and 6.0 μM, respectively. Compound 4 exhibited greater selectivity against the p53(-/-)+p53(N236S)+H-RasV12 cells (IC50 5.5 μM) than against the WT MEFs cells (IC50 14.3 μM).

Cytotoxic Cycloartane Triterpenes of the Traditional Chinese Medicine “Shengma” (Cimicifuga dahurica)

Twelve new 9,19-cycloartane triterpenes (1-12), together with fourteen known compounds (13-26), were isolated from the roots of Cimicifuga dahurica. Their structures were determined by application of spectroscopic analyses and chemical methods. Biological evaluation of the compounds against human HL-60, SMMC-7721, A549, MCF-7, and SW-480 cell lines indicated that cimigenol-type glycosides (1-3, 19, and 20) showed broad-spectrum and moderate cytotoxicities, with IC50 values ranging from 4.2 to 14.5 µM. Meanwhile, cimigenol-type aglycones (6-8, 15, 16, and 18) exhibited broad-spectrum and week cytotoxicities, having IC50 values around 20 µM. In addition, the key points of the structure-activity relationships of aglycones with a cimigenol skeleton were discussed.

Six new physalins from Physalis alkekengi var. franchetii and their cytotoxicity and antibacterial activity.

Six new physalin steroids, 7β-methoxylisophysalin B (1), 7β-methoxylphysalin C (2), physalin V (3), physalin VI (4), physalin VII (5), isophysalin I (6), together with 20 known physalins (7-26) were isolated from calyces of Physalis alkekengi var. franchetii. Structures of the new compounds were revealed through 1D and 2D NMR and mass spectroscopic methods. Compounds 1-26 were evaluated for cytotoxicity against human HL-60, SMMC-7721, A-549, MCF-7 and SW-480, and the results indicated that compounds 8, 11, and 14 displayed potent cytotoxicities (IC50<5μM) in vitro. Further antibacterial assay indicated that compounds 8, 14, and 19 showed high antibacterial activities against Bacillus subtilis and Escherichia coli.

Cytotoxic 9,19-cycloartane triterpenes from the aerial parts of Cimicifuga yunnanensis.

Six new 9,19-cycloartane triterpenes (1-6) were isolated from the aerial parts of Cimicifuga yunnanensis. The new chemical structures were determined by extensive analyses of 1D and 2D NMR spectroscopy. Compounds 1 and 2 are the first 9,19-cycloartane triterpenes characterized by CH₃-18 shifting from C-13 to C-12 in the Cimicifuga spp. The evaluation of inhibition activity against human HL-60, SMMC-7721, A-549, MCF-7, and SW480 cell lines indicated that compounds 1-6 showed different levels of cytotoxic activities with IC₅₀ values ranging from 1.2 to 27.8 μm.

New potential beneficial effects of actein, a triterpene glycoside isolated from Cimicifuga species, in breast cancer treatment.

Actein is a triterpene glycoside isolated from the rhizomes of Cimicifuga foetida (Chinese herb “shengma”) which could inhibit the growth of breast cancer cells. Nevertheless, the effect of actein on angiogenesis, which is an essential step for tumor growth and metastasis, has never been reported. Hence, this study aimed to investigate the in vitro and in vivo effects of actein on angiogenesis using human microvascular endothelial cells (HMEC-1), matrigel plug and tumor-bearing mouse models. Our results showed that actein significantly inhibited the proliferation, reduced the migration and motility of endothelial cells, and it could suppress the protein expressions of VEGFR1, pJNK and pERK, suggesting that JNK/ERK pathways were involved. In vivo results showed that oral administration of actein at 10 mg/kg for 7 days inhibited blood vessel formation in the growth factor-containing matrigel plugs. Oral actein treatments (10–15 mg/kg) for 28 days resulted in decreasing mouse 4T1 breast tumor sizes and metastasis to lungs and livers. The apparent reduced angiogenic proteins (CD34 and Factor VIII) expressions and down-regulated metastasis-related VEGFR1 and CXCR4 gene expressions were observed in breast tumors. Our novel findings provide insights into the use of actein for development of anti-angiogenic agents for breast cancer.

New Anti-angiogenic Leading Structure Discovered in the Fruit of Cimicifuga yunnanensis

Cimyunnins A–C (1–3), characterized with an unusual fused cyclopentenone ring G, together with cimyunnin D (4), possessing a highly rearranged γ-lactone ring F, were characterized from the fruit of Cimicifuga yunnanensis. Their structures were elucidated by spectroscopic analysis, X-ray diffraction, and density functional theory calculations. In addition, cimyunnin A exhibited comparable anti-angiogenic activities to those of sunitinib, a clinically-used first-line angiogenesis inhibitor, in the in vitro and ex vivo studies.

Cucurbitane triterpenoids from Hemsleya penxianensis

Two new cucurbitacins, jinfushanencins A (1) and B (2), seven new cucurbitane glycosides, jinfushanosides E-K (3–9), along with nine known analogues, were obtained from the tubers of Hemsleya penxianensis. Their structures were elucidated on the basis of extensive spectroscopic and chemical methods. Selected isolates were tested their anti-HIV-1 activities, and compound 5 showed weak anti-HIV-1 in C8166 cell (EC50 = 5.9 µg/mL) with a selectivity index of 13.5.

A cytotoxic 4α-methyl steroid from the aerial parts of Cimicifuga foetida L

A new 4α-methyl sterol, cimisterol A (1), together with five known compounds (2-6), were isolated from the aerial parts of Cimicifuga foetida L. The new compounds structure was determined with the help of extensive 1D and 2D NMR spectroscopy. Compound 1 exhibited broad-spectrum and potent cytotoxic activities against human HL-60, Jurkat, K562, U937, HepG-2, and SGC-7091 cell lines, with IC(50) values of 7.23, 2.89, 6.88, 3.38, 4.21, and 4.89 μM, respectively. Compound 3 showed moderate to weak activities to all cell lines, except for SGC-7091, having IC(50) values ranging from 13.37 to 17.72 μM. This is the first time a cytotoxic 4α-methyl sterol constituent was discovered from Cimicifuga spp.