Toxicity assessment of 3-O-[6-deoxy-3-O-methyl-ß-D-allopyranosyl-(1 → 4)-ß-D-oleandropyranosyl]-17ß-marsdenin isolated from Gongronema latifolium leaf on selected brain and kidney function indices in mice.

The safety of bioactive compounds, especially those isolated from medicinal plants, is a major concern for health authorities, pharmaceutical industries, and the public. Of recent, anti-tumor pregnane glycosides were isolated from Gongronema latifolium leaf, of which the toxicity of one, 3-O-[6-deoxy-3-O-methyl-ß-D-allopyranosyl-(1 â†’ 4)-ß-D-oleandropyranosyl]-17ß-marsdenin (3DMAOM), has not been evaluated. This study, therefore, evaluated the effects of 3DMAOM on selected brain and kidney function indices in mice. Female Swiss albino mice were randomly administered 5% dimethyl sulphoxide and different doses of 3DMAOM (0.5, 1, 2, and 4 mg/kg body weight) for fourteen (14) days, and their blood, brains, and kidneys were collected for biochemical analysis. There was no significant alteration in the activities of alkaline phosphatase (ALP), acetylcholinesterase, creatine kinase, Na+/K+-ATPase, Ca2+/Mg2+-ATPase, and Mg2+-ATPase in the brain of the treated groups compared to control. Also, no significant changes in the activities of ALP, gamma-glutamyltransferase, Na+/K+-ATPase, Ca2+/Mg2+-ATPase, and Mg2+-ATPase in the kidney of the treated groups compared to control. The plasma concentrations of Na+, K+, Cl-, PO43-, creatinine, and urea of mice were not significantly altered at all doses of the 3DMAOM compared to controls. However, the plasma concentration of Ca2+ was significantly reduced (p < 0.05) at all doses of the 3DMAOM, and the plasma concentration of uric acid was significantly reduced (p < 0.05) at 2 mg/kg body weight of the 3DMAOM compared to controls. These findings suggest that 3DMAOM isolated from Gongronema latifolium leaf may not adversely affect brain function but may affect calcium ion homeostasis in subjects.

Effects of Cysteine-Stabilised Peptide Fraction of Aqueous Extract of Morinda lucida Leaf on Selected Cardiovascular Disease Indices in Mice.

This study evaluated the effects of cysteine-stabilised peptide fraction (CSPF) of aqueous extract of Morinda lucida leaf on selected cardiovascular disease indices in mice. Sixty adult Swiss Albino mice were randomly divided into 6 groups (n = 10). Group A served as control and received 5% DMSO. Half of the mice in groups B, C, D, E and F received 31.25, 62.5, 125, 250, and 500 mg/kg body weight of CSPF respectively for 7 days while the other half received the various doses for 28 days. After the experimental period, selected cardiovascular disease indices were determined in the mice. The results revealed that CSPF significantly reduced (p < 0.05) atherogenic index, plasma concentrations of total cholesterol and LDL-cholesterol but significantly increased (p < 0.05) plasma HDL-cholesterol concentration at higher doses after 28 days of administration. Plasma lactate dehydrogenase, aspartate aminotransferase and alkaline phosphatase activities were not significantly altered (p > 0.05) at all doses of the CSPF after 7 and 28 days of administration  compared to controls. After 7 days of CSPF administration, the activities of heart Ca2+, Mg2+-ATPase and Na+-K+-ATPase were not significantly altered (p > 0.05) but heart Mg2+-ATPase activity was significantly increased (p < 0.05) at 250 mg/kg body weight compared to controls. Also, 28 days of CSPF administration at all doses had no significant effect (p > 0.05) on the activities of heart Mg2+-ATPase and Na+-K+-ATPase of mice compared to controls but heart Ca2+-Mg2+-ATPase activity was significantly increased (p < 0.05) at the highest dose with no significant alteration (p > 0.05) at other doses compared to controls. Generally, CSPF administration had no significant effect (p > 0.05) on haematological parameters after 7 and 28 days. These results suggest that CSPF may not predispose subjects to cardiovascular diseases.

Effects of Cysteine-stabilized Peptide Fraction of Morinda lucida Leaf on Selected Kidney Function Indices in Mice.

OBJECTIVE: This study evaluated the effect of cysteine-stabilized peptide fraction (CSPF) of Morinda lucida leaf on selected kidney function indices in mice. METHODS: Sixty mice were assigned into six groups. Group A served as the control while groups B, C, D, E and F received 31.25, 61.5, 125, 250, and 500 mg/kg body weight of CSPF respectively for 7 or 28 days. RESULTS: Administration of CSPF for 7 and 28 days caused no significant (p>0.05) alteration in kidney-body weight ratio, plasma concentrations of the selected electrolytes, urea and creatinine at all doses compared to controls. However, plasma uric acid concentration was significantly increased (p<0.05) after administration of CSPF for 7 days at doses of 125 and 500 mg/kg body weight while it was significantly reduced (p<0.05) after administration for 28 days at doses higher than 31.25 mg/Kg body weight compared to controls. The activities of Ca2+, Mg2+-ATPase and Na+, K+-ATPases in the kidney and the histology of the kidney remained unaltered (p>0.05) throughout the experimental period compared to controls. CONCLUSION: CSPF may adversely affect uric acid metabolism after prolonged administration.

Mesoporous silica nanocarriers encapsulated antimalarials with high therapeutic performance.

The use of nanocarriers in drug delivery is a breakeven research and has received a clarion call in biomedicine globally. Herein, two newly nano-biomaterials: MCM-41 encapsulated quinine (MCM-41 ⊃ QN) (1) and 3-phenylpropyl silane functionalized MCM-41 loaded QN (pMCM-41 ⊃ QN) (2) were synthesized and well characterized. 1 and 2 along with our two already reported nano-antimalarial drugs (MCM-41 ⊃ ATS) (3) and 3-aminopropyl silane functionalized MCM-41 contained ATS (aMCM-41 ⊃ ATS) (4) were screened in vitro for their activity against P. falciparium W2 strain, cytotoxicity against BGM cells and in vivo for their activity against Plasmodium bergheiNK65. 1 has the highest antimalarial activity in vivo against P. berghei NK65, (ED50: < 0.0625 mg/kg body weight) and higher mean survival time compared to the other nano biomaterials or unencapsulated drugs at doses higher than 0.0625 mg/kg body weight. This encapsulation strategy of MCM-41 ⊃ QN (1) stands very useful and effective in delivering the drug to the target cells compared to other delivery systems and therefore, this encapsulated drug may be considered for rational drug design.

Iloneoside: a cytotoxic ditigloylated pregnane glycoside from the leaves of Gongronema latifolium Benth.

Gongronema latifolium Benth (Asclepiadaceae) is an edible-green-leafy vegetable with known medicinal value. A chemical investigation of the 80% methanolic extract of the leaves led to the isolation of a new pregnane glycoside: iloneoside (3-O-[6-deoxy-3-O-methyl-ß-D-allopyranosyl-(1→14)-ß-D-oleandropyranosyl]-11,12-di-O-tigloyl-17ß-marsdenin), together with four known constituents. Their chemical structures were determined by spectroscopic analysis. The isolates were tested for their in vitro growth inhibitory activity against human leukemia HL-60 cells. Iloneoside was the most active and gave apoptotic response. Molecular docking analysis demonstrated that iloneoside could be accommodated within hot spots of anti-apoptotic protein Bcl-2. These results suggest G. latifolium as a reliable source of potent anticancer compounds.

In vivo antimalarial activity and toxicological effects of methanolic extract of Cocos nucifera (Dwarf red variety) husk fibre.

OBJECTIVE: Phytochemical constituents as well as antimalarial and toxicity potentials of the methanolic extract of the husk fibre of Dwarf Red variety of Cocos nucifera were evaluated in this study. METHODS: The dried powdered husk fibre was exhaustively extracted with hexane, ethyl acetate and methanol successively and the methanolic extract was screened for flavonoids, phenolics, tannins, alkaloids, steroids, triterpenes, phlobatannins, anthraquinones and glycosides. A 4-day suppressive antimalarial test was carried out using Plasmodium berghei NK65-infected mice, to which the extract was administered at doses of 31.25, 62.5, 125, 250 and 500 mg/kg body weight (BW). Toxicity of the extract was evaluated in rats using selected hematological parameters and organ function indices after orally administering doses of 25, 50 and 100 mg/kg BW for 14 d. RESULTS: Phytochemical analysis revealed the presence of alkaloids, tannins, phenolics, saponins, glycosides, steroids and anthraquinones in the extract. Moreover, the extract reduced parasitemia by 39.2% and 45.8% at doses of 250 and 500 mg/kg BW respectively on day 8 post-inoculation. Various hematological parameters evaluated were not significantly altered (P>0.05) at all doses of the extract, except red blood cell count which was significantly elevated (P<0.05) at 100 mg/kg BW. The extract significantly increased (P<0.05) urea, creatinine, cholesterol, high-density lipoprotein-cholesterol and bilirubin concentrations in the serum as well as atherogenic index, while it reduced albumin concentration significantly (P<0.05) at higher doses compared to the controls. Alanine aminotransferase activity was reduced in the liver and heart significantly (P<0.05) but was increased in the serum significantly (P<0.05) at higher doses of the extract compared to the controls. CONCLUSION: The results suggest that methanolic extract of the Dwarf red variety has partial antimalarial activity at higher doses, but is capable of impairing normal kidney and liver function as well as predisposing subjects to cardiovascular diseases.

In vivo antimalarial activity and toxicological effects of methanolic extract of Cocos nucifera (Dwarf red variety) husk fibre / 中西医结合学报

Phytochemical constituents as well as antimalarial and toxicity potentials of the methanolic extract of the husk fibre of Dwarf Red variety of Cocos nucifera were evaluated in this study.