Cytotoxicity of alkaloids isolated from peganum harmala seeds

Ethnopharmacological relevance: Peganum harmala is used in traditional medicine to treat a number of diseases including cancer. Our preliminary studies show that the alkaloidal extract of PH seed is cytotoxic to several tumor cell lines in vitro and has antitumor effect in a tumor model in vivo. The present investigation was aimed at extending our previous studies in identifying the components in P. harmala seedextract responsible for the cytotoxic effects, and study the cytotoxic and antiproliferative activity of isolated alkaloids and total alkaloidal fraction [TAF] in several tumor cell lines. Four alkaloids: harmalicidine, harmine, peganine [vasicine] and vasicinone were isolated from the P. harmala seedextract and their activity and that of TAF were tested a] for their cytotoxic activity against four tumor cell lines [three developed by us by chemical-induction in Wistar rats: 1] Med-mek carcinoma ; 2] UCP-med carcinoma ; 3] UCP-med sarcoma]; and 4] SP2/O-Ag14, and b] for antiproliferative effect on cells of Jurkat, E6-1 clone [inhibition of incorporation of [[3]H-thymidine] in cellular DNA]. The alkaloids and TAF inhibited the growth of tumor cell lines to varying degrees; Sp2/O-Ag14 was the most sensitive, with IC[50] values [concentration of the active substance that inhibited the growth of the tumor cells by 50%] ranging between 2.43 microg/mL and 19.20 microg/mL, while UCP-med carcinoma was the least sensitive [range of IC[50] = 13.83 microg/mL to 59.97 microg/mL]. Of the substances evaluated, harmine was the most active compound [IC[50] for the 4 tumor cell lines varying between 2.43 microg/ml and 18.39 microg/mL], followed by TAF [range of IC[50] = 7.32 microg/mL to 13.83 microg/mL]; peganine was the least active [IC[50] = 50 microg/mL to > 100 microg/ml]. In terms of antiproliferative effect, vasicinone and TAF were more potent than other substances: the concentration of vasicinone, and TAF needed to inhibit the incorporation of [[3]H-TDR] in the DNA cells of Jurkat, E6-1 clone by 50% [IC[50]] were 8.60 +/- 0.023 microg/mL and 8.94 +/- 0.017 microg/mL, respectively, while peganine was the least active [IC[50] >100 microg/mL]. The IC[50] values for harmalacidine [27.10 +/- 0.011 microg/mL] and harmine [46.57 +/- 0.011 microg/mL] were intermediate. The harmala alkaloids inhibited the growth of four tumor cell lines, and proliferation of Jurkat cells with varying potencies. Harmine was the most potent in inhibiting cell growth, and vasicinone was most active as antiproliferating substance. The TAF had significant cytotoxic as well as antiproliferating activity

Hypoglycemic and hypolipidemic effects of an aqueous extract of chamaerops humilis leaves in obese, hyperglycemic and hyperlipidemic meriones SHAWI rats

Ethnopharmacological relevance: An aqueous concoction made from the leaves of Chamaerops humilis [L.] [dwarf fan palm], is used in the Moroccan traditional medicine for the treatment of diabetes, as well as a number of other diseases. The aim of the study was to experimentally validate the use of C. humilis in the folk treatment of diabetes as well as to determine if the aqueous leaf extract of this plant has hypolipidemic properties in an animal model of obesity, hyperglycemia and hyperlipidemia. The animal model consisted of experimentally induced obesity, hyperglycemia and hyperlidemia [OHH] in Meriones shawi rats. In the acute study, OHH M. shawi rats [n = 8] were given a single oral dose [10 mg/kg] of an aqueous extract of C. Humilis leaves [plant-extract]; taurine [8 mg/kg] was used as the positive control. Plasma glucose levels were determined at 2-, 4- and 6-hr after the dose. In the sub-chronic study, groups of OHH rats [n = 8 for each group] were given daily oral doses of the plant-extract and taurine [at the above doses] for 30 days. Body weight [BW], plasma glucose, total cholesterol and triglycerides were measured at 15 and 30 days of dosing. The M. shawi rats developed OHH when maintained on a hypercaloric diet and forced physical inactivity for 90 days. A single oral dose of the plant-extract decreased plasma glucose levels with the maximum effect occurring at 4-hr after the dose [6.88 +/- 1.38 mmol/L compared to baseline 12.04 +/- 0.94 mmol/L; P<0.01]. Taurine also decreased plasma glucose [from 12.26 +/- 1.27 mmol/L to 9.15 +/- 1.27 mmol/L; P<0.05]; water treated control group did not show any effect. In normal M. shawi [normal] rats, none of the treatments had significant effect on glucose levels. In the sub-chronic study, daily oral administration of the plant-extract or taurine for 30 days to the OHH rats resulted in a significant decrease in BW [from 241 +/- 8 g to 165 +/- 11 g; P<0.001 for the extract, and from 221 +/- 13 g to 189 +/- 11 g; P<0.05 for taurine]; water treated control rats showed no effect. In normal rats, administration of the plant-extract or taurine for 30 days resulted in an insignificant decrease in BW, while water administration caused a small [normal] increase in the weight Plasma glucose levels of the OHH rats decreased significantly with daily dosing with the plant-extract [from baseline 12.04 +/- 0.94 mmol/L to 6.10 +/- 0.27 mmol/L [P<0.05] after 15 days, and to 4.84 +/- 0.22 mmol/L [P<0.001] after 30 days]. Taurine was less effective [P<0.05], while water treated control group did not show any effect. In the normal rats, administration of the plant-extract or taurine for 30 days resulted in a small decrease in glycemia. Administration of plant-extract caused a significant decrease in plasma levels of total cholesterol [from baseline of 3.46 +/- 0.21 mmol/L to 1.05 +/- 0.06 mmol/L [p<0.0l] after 15 days and to 0.62 +/- 0.02 mmol/L [p<0.00l]] after 30 days, and triglycerides [from baseline of 1.15 +/- 0.17 mmol/L to 0.47 +/- 0.04 mmol/L [p<0.00l] after 15 days and to 0.37 +/- 0.03 mmol/L [p<0.001] after 30 days]. Taurine was less effective, while water treated control group did not show any effect. There was no effect of these treatments on lipid levels in normal rats. The results of this study validate the traditional use of the leaves of C. humilis in the treatment of diabetes in Morocco. Since, the aqueous leaf extract also decreased total cholesterol and triglycerides, the plant may also be useful in the management of secondary complications of diabetes [dyslipidemia] Furthermore, the plant may become a good source of antidiabetic medication

Ethnopharmacology of the plants of genus Ajuga

The plants of genus Ajuga are evergreen, clump-forming rhizomatous perennial or annual herbaceous flowering species, with Ajuga being one of the 266 genera of the family Lamiaceae. There are at least 301 species of the genus Ajuga with many variations. These plants, growing in Europe, Asia, Africa, Australia and North America, are used in gardens as ground cover or border for their foliage and beautiful flowers. Many of these plants have been used in traditional medicine as a remedy for fever, toothache, dysentery, malaria, high blood pressure, diabetes, gastrointestinal disorders, as anthelmintic, diuretic and antifungal, anti-inflammatory, and antimycobacterial agents. They are also used as insect growth inhibitor s. A large number of compounds have been isolated from the Ajuga plants, including phytoecdysteroids, Neo-clerodane-diterpenes and diterpenoids, triterpenes, sterols, anthocyanidin-glucosides and iridoid glycosides, withanolides, flavonoids, triglycerides and essential oils. These compounds possess a broad spectrum of biological, pharmacological and medicinal properties, such as anabolic, analgesic, antibacterial, antiestrogenic, antifungal, anti-inflammatory, antihypertensive, antileukemic, antimalarial, antimycobacterial, antioxidant, antipyretic, cardiotonic, cytotoxic, hypoglycemic, and vasorelaxing activity, as well as antifeedant and insect growth-inhibitory properties. Thus, genus Ajuga has significant medicinal and economic importance

Acute hypoglycemic, hypocholesterolemic and hypotriglyceridemic effects of continuous intravenous infusion of a lyophilised aqueous extract of Ajuga iva l. Schreber whole plant in streptozotocin-induced diabetic rats

The hypoglycemic and hypolipidemic effect of continuous intravenous infusion of a lyophilised aqueous extract of the whole plant Ajuga iva [L.] Schreber [Labiatae] [Al-extract] was investigated in anesthetized normal and streptozotocin [STZ]-induced diabetic rats. The Al-extract was administered to a group of rats by continuous intravenous infusion for 4 h at a dose of 4.2 microg/min/l00g body weight; another group was infused with taurine, the reference compound, at the same dose. In normal rats, Al-extract infusion had no effect on plasma glucose or triglycerides, but plasma cholesterol levels were significantly decreased [22%; P<0.05]. However, taurine infusion produced significant hypoglycemic, hypocholesterolemic and hypotriglyceridemic effects [all changes, P<0.05]. In STZ-diabetic rats, Al-extract infusion reduced plasma levels of glucose by 24% [P<0.05], cholesterol by 35% [P<0.01] and triglycerides by 13% [P<0.05]. Infusion with taurine produced a greater fall in plasma glucose [72%, P<0.01], cholesterol [54%; P < 0.001] and triglyceride [24%; P < 0.001] levels. Our results indicate that intravenously administered Al-extract exerts hypoglycemic and hypolipidemic effects in diabetic rats by mechanism [s] which appear to be similar to that of taurine, which involve insulin sensitization or an insulin-like effect. The identity and the exact mechanism [s] of action of the active component [s] of the Al-extract are not known. Ajuga iva appears to be a useful plant in the therapy of diabetes, a condition in which hyperglycemia and dyslipidemia coexist quite often