Bioactive Triterpenes from the Root of Salvia miltiorrhiza Bunge

Danshen (Salvia miltiorrhiza) is a well‐known medicinal herb in the oriental medicine. The current study on bioactive triterpenoid in the root of S. miltiorrhiza led to the isolation of a new highly hydroxylated ursane‐type triterpene, urs‐12‐ene‐2α,3β,7β,16α‐tetraol (1) and five known ones including 2β‐hydroxypomolic acid (2), maslinic acid (3), asiatic acid (4), ursolic acid (5), and oleanolic acid (6). Their structures were elucidated on the basis of extensive spectroscopic analyses and comparison with literature data. The antiproliferative testing against HL‐60 cells revealed that the new compound 1 and ursolic acid (5) showed weak and moderate activities with IC₅₀ values of 42.2 and 11.7 μM. In addition, compounds 1–3 showed inhibitory effect on ghrelin activity. Copyright © 2017 John Wiley & Sons, Ltd.     

Antioxidant,antimutagenic and antiproliferative activities in selected seaweed species from Sinaloa,Mexico

Context Seaweeds from the Mexican Pacific Ocean have not been evaluated as a source of chemoprotectants.

Objective The objective of this study is to evaluate chemopreventive activities of the seaweeds Phaephyceae – Padina durvillaei (Dictyotaceae) – Rodhophyceae – Spyridia filamentosa (Spyridiaceae), Gracilaria vermiculophylla (Gracilariaceae) – and Chlorophyceae – Ulva expansa (Ulvaceae), Codium isabelae (Codiaceae), Rhizoclonium riparium (Cladophoraceae) and Caulerpa sertularioides (Caulerpaceae).

Materials and methods Methanol, acetone and hexane seaweed extracts were assessed at 30 and 3?mg/mL on antioxidant capacity (DPPH and ABTS assays), 0.003–3.0?mg/plate on antimutagenic activity against AFB₁ using Salmonella typhimurium TA98 and TA100 tester strains in Ames test, and 12.5 to 100?μg/mL on antiproliferative activity on Murine B-cell lymphoma. Phenols, flavonoids and pigments content were also assessed as antioxidant compounds.

Results Extraction yield was higher in methanol than in acetone and hexane extracts (6.4, 2.7 and 1.4% dw). Antioxidant capacity was higher in brown and green than in red seaweed species, particularly in P. durvillaei extracted in acetone (EC_50? value=_?16.9 and 1.56?mg/mL for DPPH and ABTS). Flavonoids and chlorophylls were identified as mainly antioxidant components; particularly in hexane extracts, which were correlated with the antioxidant capacity. Highest mutagenesis inhibition (>?40%) occurred in R. riparium at the lowest concentration assayed (0.003?mg/plate), while highest antiproliferative inhibition (37 and 72% for 12.5 and 25?μg/mL) occurred in C. sertularioides.

Discussion and conclusion Flavonoids and chlorophylls explained the chemopreventive activities assessed in S. filamentosa, R. riparium and C. sertularioides. These seaweeds have a high potential as a source of novel chemoprotectants.     

Design,synthesis, and molecular docking study of new monastrol analogues as kinesin spindle protein inhibitors

Lung, colorectal, and breast cancers are the top three types of cancer by incidence and are responsible for one-third of the cancer incidence and mortality. A series of 18 3,4-dihydropyrimidine analogues bearing a 1,2-methylenedioxybenzene component at position 4 with diverse side chains at positions 5 and 6 was designed and synthesized as inhibitors of the Eg5 kinesin enzyme. Target compounds were screened for their anticancer activity according to the NCI-USA protocol toward a panel of 60 cancer cell lines. Compounds 12a and 12b displayed the best antiproliferation activity against many cell lines. Interestingly, compound 12a displayed lethal effects against non-small-cell lung cancer NCI-H522 cells (−42.26%) and MDA-MB-468 breast cancer cells (−1.10%) at a single-dose assay concentration of 10⁻⁵ M. Compounds 11c, 11d, 11g, 12a – d, 13, 15 , and 18a were assayed against the kinesin enzyme, with IC₅₀ values ranging from 1.2 to 18.71 μM, which were more potent compared with monastrol (IC₅₀ = 20 μM). Cell cycle analysis of NCI-H522 cells treated with compound 12a showed cell cycle arrest at the G2/M phase. Furthermore, the expression levels of active caspase-3 and -9 were measured. A molecular docking study was performed for some demonstrative compounds as well as monastrol docked into the allosteric binding site of the kinesin spindle protein.     

糖皮质激素及其受体对细胞数量稳态调节的作用

糖皮质激素(GC)/糖皮质激素受体(GR)能够抑制体内多种细胞的增殖,近年来还发现GC/GR对多种凋亡诱导因子导致的细胞凋亡具有拮抗作用。我们因此提出GC/GR可能通过上述作用来维持细胞数量的稳定,这种对细胞数量的稳态调节可能是GC/GR对机体稳态调节的一个重要方面。本文结合我们自身的工作综述了GC/GR抑制细胞增殖和抗凋亡的作用,并简述了其作用机制的研究进展。这方面的研究有助于充分了解GC的生理和药理作用以及副作用产生的机制,有助于临床合理用药。     

Ginger's (Zingiber officinale Roscoe) inhibition of rat colonic adenocarcinoma cells proliferation and angiogenesis in vitro

Ginger's (Zingiber officinale Roscoe) natural bioactives, specifically ginger extract and 6‐gingerol, were measured for their in vitro inhibition of two key aspects of colon cancer biology – cancer cell proliferation and angiogenic potential of endothelial cell tubule formation. Ginger extract was obtained via column distillation, while the 6‐gingerol was purchased from Calbiochem. Antiproliferation activity was assessed through tritiated thymidine ([³H]Tdr) incorporation studies of YYT colon cancer cells; the anti‐angiogenic ability of gingerol was assessed by a Matrigel assays using MS1 endothelial cells. These selected ginger bioactives had: 1) a direct effect on YYT rat cancer cell proliferation (6–1.5% ginger extract; 100–4 µM 6‐gingerol); 2) an indirect effect on MS1 endothelial cell function either at the level of endothelial cell proliferation or through inhibition of MS1 endothelial cell tube formation (100–0.8 µM). Compound 6‐gingerol was most effective at lower doses in inhibiting endothelial cell tube formation. These in vitro studies show that 6‐gingerol has two types of antitumor effects: 1) direct colon cancer cell growth suppression, and 2) inhibition of the blood supply of the tumor via angiogenesis. Further research is warranted to test 6‐gingerol in animal studies as a potential anticancer plant bioactive in the complementary treatment of cancer. Copyright © 2008 John Wiley & Sons, Ltd.     

Ellagitannin (BJA3121), an anti‐proliferative natural polyphenol compound,can regulate the expression of MiRNAs in HepG2 cancer cells

MicroRNAs (miRNAs) play an important role in cancers. A number of miRNA expression‐profiling studies have been done to identify the miRNA signatures of cancers from different cellular origin. There is, however, relatively little information on how anticancer agents regulate miRNA expression. Ellagitannin (BJA3121), 1,3‐Di‐O‐galloyl‐4,6‐(s)‐HHDP‐b‐D‐glucopyranose, is a new natural polyphenol compound isolated from Balanophora Japonica MAKINO. Our preliminary results have shown that BJA3121 had antiproliferative effect and modified the expression of different genes in human HepG₂ cancer cells. In this study, we further evaluate whether this antineoplastic compound is able to alter miRNA expression in HepG₂ cells. We demonstrated for the first time that BJA3121 can regulate the expression of 25 miRNAs, including 17 upregulated and 8 downregulated miRNAs in HepG₂ cells. Our results suggested that BJA3121‐modifed miRNA expression can mediate, at least in part, the antiproliferative and multigene regulatory action induced by the compound on HepG₂ cancer cells. Copyright © 2009 John Wiley & Sons, Ltd.     

Insights into the In Vitro Antitumor Mechanism of Action of a New Pyranoxanthone

Naturally occurring xanthones have been documented as having antitumor properties, with some of them presently undergoing clinical trials. In an attempt to improve the biological activities of dihydroxyxanthones, prenylation and other molecular modifications were performed. All the compounds reduced viable cell number in a leukemia cell line K-562, with the fused xanthone 3,4-dihydro-12-hydroxy-2,2-dimethyl-2H,6H-pyrano[3,2-b]xanthen-6-one (5) being the most potent. The pyranoxanthone 5 was particularly effective in additional leukemia cell lines (HL-60 and BV-173). Furthermore, the pyranoxanthone 5 decreased cellular proliferation and induced an S-phase cell cycle arrest. In vitro, the pyranoxanthone 5 increased the percentage of apoptotic cells which was confirmed by an appropriate response at the protein level (e.g., PARP cleavage). Using a computer screening strategy based on the structure of several anti- and pro-apoptotic proteins, it was verified that the pyranoxanthone 5 may block the binding of anti-apoptotic Bcl-xL to pro-apoptotic Bad and Bim. The structure-based screening revealed the pyranoxanthone 5 as a new scaffold that may guide the design of small molecules with better affinity profile for Bcl-xL.     

Antimutagenic and antiproliferative effects of roasted and defatted peanut dregs on human leukemic U937 and HL-60 cells

The antimutagenic effects on Salmonella typhimurium TA98 and TA100 strains and antiproliferative effects on leukemia cell lines (U937 and HL-60) of peanut protein isolate (PPI), peanut protein isolate enzyme hydrolysate (PPIEH), roasted and defatted peanut dregs (RDPD), and roasted and defatted peanut dregs enzyme hydrolysate (RDPDEH) were investigated. The antimutagenic effects on B(a)P and 4-NQO toward the TA98 and TA100 strains were found to follow a diminishing order: RDPD > RDPDEH > PPI = PPIEH with dose-dependency. Antiproliferative effects on leukemia cells U937 and HL-60 were also detected. RDPD was found to be the most effective of all the peanut preparations. At 100 microg/mL concentration, RDPD inhibited the proliferation of U937 and HL-60 cells by 56% and 52%, respectively. We propose to consider RDPD and RDPDEH in the development of natural chemotherapeutic or chemopreventive dietary supplements against leukemia and to upgrade the utilization of these by-products in peanut oil production.     

壳聚糖及其衍生物对肝癌细胞SMMC7721的生长抑制作用

目的观察壳聚糖及其衍生物对肝癌细胞SMMC7721的生长抑制作用。方法采用四甲基偶氮唑盐(MTT)法研究了不同浓度水溶性壳聚糖、磺化壳聚糖、羧甲基壳聚糖和壳寡糖对肝癌细胞株SMMC7721的生长抑制作用。结果在4种不同壳聚糖及其衍生物中,水溶性壳聚糖和磺化壳聚糖可显著抑制肝癌细胞的生长,并在一定范围内(50~400 mg/L)呈剂量依赖关系,其中以磺化壳聚糖最为显著,羧甲基壳聚糖和壳寡糖对肝癌细胞无生长抑制作用。结论壳聚糖及其衍生物可抑制肝癌细胞的生长,并且呈剂量依赖关系。