Cancer chemopreventive activity of terpenoid coumarins from Ferula species

Several natural products have been found to have anti-tumor promoting activity. In the present study, we carried out a primary screening of ten terpenoid coumarins isolated from plants of the Ferula species, examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12- O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells. Auraptene (7-geranyloxycoumarin, 1) and umbelliprenin (7-farnesyloxycoumarin, 2) were found to significantly inhibit EBV-EA activation and preserved the high viability of Raji cells, suggesting that they might be valuable anti-tumor-promoting agents (IC (50) 8.3 and 9.1 nM, respectively). Our findings revealed that the presence of a prenyl moiety in the terpenoid coumarins plays an important role in anti-tumor promoting activity as previously reported for xanthones, coumarins, flavonoids and phenylpropanoids.     

Hypolipemic and potential antiatherosclerotic properties of diprophyllinyl-4-benzyloxybenzoate

To assess the hypolipemic and antiatherosclerotic activity of diprophyllinyl-4-benzyloxybenzoate guinea-pigs were kept on a high-lipid diet alone or with the tested compound for 21 days, and rabbits--for 3 months. It was found that diprophyllinyl-4-benzyloxybenzoate displays a distinct hypolipemic activity, particularly with respect to cholesterol, both in guinea-pigs and rabbits. It also depresses the cholesterol and the trigliceride content in liver homogenates and shows a tendency to normalize the low-density-lipoprotein fraction in guinea-pigs, as well as cholesterol of the high-density lipoprotein fraction, and malon dialdehyde in rabbits. The area of intima covered with atheromatous plaques was smaller in rabbits receiving the high-lipid diet with diprophyllinyl-4-benzyloxybenzoate than in those receiving that diet alone.     

Trimerization of apolipoprotein A-I retards plasma clearance and preserves antiatherosclerotic properties

An increased plasma level of the major high-density lipoprotein (HDL) component, apolipoprotein A-I (apoA-I) is the aim of several therapeutic strategies for combating atherosclerotic disease. HDL therapy by direct intravenous administration of apoA-I is a plausible way; however, a fast renal filtration is a major obstacle for this approach. Using protein engineering technology, we have fused apoA-I to the trimerization domain of human tetranectin and thus constructed a high-mass recombinant trimeric apoA-I variant. The recombinant fusion protein was stable and expressed well; upon purification and intravenous injection into mice, it exhibited prolonged plasma retention time compared to wild type apoA-I. Trimeric apoA-I was biologically active in terms of promoting cholesterol efflux, stimulation of lecithin cholesterol acyltransferase-mediated cholesterol esterification, and reducing progression of atherosclerosis in cholesterol-fed low-density lipoprotein receptor-deficient mice. Direct administration of recombinant high-mass apoA-I analogues with retarded clearance is therefore a potential novel therapeutic approach for atherosclerotic plaque stabilization.     

Hypolipidaemic and antiatherosclerotic effects of plumbagin in rabbits

Plumbagin (2-methyl-5-hydroxy, 1:4 naphthoquinone) isolated from the roots of Plumbago zeylanica when administered to hyperlipidaemic rabbits, reduced serum cholesterol and LDL-Chol. by 53 to 86 percent and 61 to 91 percent respectively. It lowered cholesterol/phospholipid ratio by 45.8 percent and elevates the decreased HDL-Chol significantly. Further, Plumbagin treatment prevented the accumulation of cholesterol and triglycerides in liver and aorta and regressed atheromatous plaques of thoracic and abdominal aorta. Plumbagin treated hyperlipidaemic subjects excreted more fecal cholesterol and phospholipids. In conclusion-Plumbagin feeding brings about a definite regression of atheroma and prevents the accumulation of cholesterol and triglycerides in liver and aorta.     

Adrenomedullin as a potent antioxidative and antiatherosclerotic substance

Adrenomedullin was originally discovered as a vasodilative peptide, but recent studies have revealed its pleiotropic effects. Among these studies, the antioxidative properties of adrenomedullin were observed in adrenomedullin knockout mice. Through its antioxidative effect, adrenomedullin can protect organs from damage induced by high blood pressure, ischemia and aging. This indicates that antioxidants that can inhibit reactive oxygen species production but do not have a scavenging effect could be a new effective therapeutic target for organ protection in hypertension as well as metabolic syndrome, in which higher oxidative stress plays a pivotal role.     

Experimental hypolipidemic and antiatherosclerotic activity of bisanions]

Experiments on rabbits with experimental cholesterol atherosclerosis have shown bisanions :formula: see text.     

Studying plant-derived coumarins for their pharmacological and therapeutic properties as potential anticancer drugs

Coumarins have attracted intense interest in recent years because of their diverse pharmacological properties. Among these properties, their anticancer effect was most extensively examined. In this review, their broad range of effects on the tumours as shown by various in vitro and in vivo experiments as well as clinical investigations is discussed. Studies have indicated that coumarins elicit inhibitory effects on cell growth of various carcinoma cell lines and may be potential candidates for cancer therapy. These natural compounds have served as valuable leads for further design and synthesis of more active analogues. In view of the relative simplicity of the coumarin compounds and their mechanism of action, the coumarin pharmacophore may serve as an important model on which to develop new patterns in cancer chemotherapy. The aim of this review is to examine in detail the properties of the title compounds as anticancer agents. In view of their comparatively low toxicity, relative cheapness, presence in the diet and occurrence in various herbal remedies, it appears important to evaluate their anticancer potentialities. Moreover their synergistic activity in combination therapy with other well-known anticancer drugs could be the basis for the development of rational approaches to new forms of cancer chemotherapy.     

Hypolipidemic activity of trimethylglycine

Hypolipidemic properties of a native trimethyl derivative of glycine, trimethylglycine (TMGl), were studied in hyperlipidemic rats and guinea pigs. The administration of TMGl to the hyperlipidemic rats and guinea pigs produced a pronounced hypolipidemic effect. A positive action of TMGl on the lipid profile of blood serum of the experimental animals was observed as manifested by a decrease in the level of cholesterol of low density lipoproteins (LDL) and an increase in the cholesterol level of high density lipoproteins (HDL).     

An efficient synthesis and antioxidant properties of novel imino and amino derivatives of 4-hydroxy coumarins

Series of imino and amino derivatives of 4-hydroxy coumarins were synthesized via conventional and microwave promoted procedure and evaluated for antioxidant potential through different in vitro models such as (DPPH) free radical scavenging activity, linoleic acid emulsion model system, reducing power assay and phosphomolybdenum method. All prepared compounds possess good antioxidant activity and among them p-nitro-phenyl derivative 6c with IC₅₀ at 25.9 μM possesses radical scavenging activity which is comparable to standard BHT, while the best reducing power was observed in a case of benzyl amino compound 8c (RP₅₀ 255.6 μM). Also, observed data indicated that compounds may serve as inhibitors of lipid peroxidation process.     

几丁糖酯抗动脉粥样硬化作用研究

用高脂膳食喂养家兔建立动脉粥样硬化模型,观察几丁糖酯对脂质代谢及主动脉斑块形成的影响,结果表明,几丁糖酯可以降低家兔血清中甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）及丙二醛（MDA）含量,升高高密度脂蛋白胆固醇（HDL-C）,减轻肝脏脂肪样变,砬轻主动脉斑块形成程度;在体外培养牛主动脉平滑肌细胞,观察几丁糖酯对细胞增殖的影响。结果表明,几丁糖酯可抑制血管平滑肌细胞增殖。透射电镜观察,给药组细胞呈现收缩型的形态学特征,而对照组则呈现合成型的特征。     

Sensitization and crossreaction of simple coumarins

The contact sensitization of 11 simple coumarins was examined by subcutaneous sensitizing of guinea pigs, and the structure-activity relationship and cross-reactivity were investigated. Esculetin, 4-methylesculetin, and dephnetin were found to be strong sensitizers, and 4-hydroxy-coumarin to be a moderate sensitizer. Other simple coumarins tested had a weak sensitivity to mild sensitizers. The results suggest that the introduction of hydroxy group, especially adjacent substitution at the 6, 7, and 8 positions of the coumarin ring with two hydroxy groups, may play an important role in exhibiting the contact sensitization activity. The cross-reactivity was observed between esculetin and 4-methylesculetin, esculin or isoscoporetin, and also between daphnetin and 4-methylumbelliferone or umbelliferone, although there was no mutual cross-reactivity between esculetin and daphnetin. It is interesting to note that guinea pigs, which had a weak sensitivity to umbelliferone, showed a strong cross-reactivity to daphnetin, while those, which had a weak sensitivity to daphnetin, showed a weak cross-reactivity to umbelliferone. It is assumed that a skin-protein conjugation at 5 or 6 positions of the coumarin ring is important to elicit the cross-reactivity of esculetin or daphnetin groups.