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Highlights • MIMO2 had myelin-potentiating effects at 10 mg/kg. • MIMO2 showed no side-effects. • MIMO2 reduced neuropathologies., Vanadium, a transition series metal released during some industrial activities, induces oxidative stress and lipid peroxidation. Ameliorative effect of a pure compound from the methanolic extract of Moringa oleifera leaves, code-named MIMO2, in 14-day old mice administered with vanadium (as sodium metavanadate 3 mg/kg) for 2 weeks was assessed. Results from body weight monitoring, muscular strength, and open field showed slight reduction in body weight and locomotion deficit in vanadium-exposed mice, ameliorated with MIMO2 co-administration. Degeneration of the Purkinje cell layer and neuronal death in the hippocampal CA1 region were observed in vanadium-exposed mice and both appeared significantly reduced with MIMO2 co-administration. Demyelination involving the midline of the corpus callosum, somatosensory and retrosplenial cortices was also reduced with MIMO2. Microglia activation and astrogliosis observed through immunohistochemistry were also alleviated. Immunohistochemistry for myelin, axons and oligodendrocyte lineage cells were also carried out and showed that in vanadium-treated mice brains, oligodendrocyte progenitor cells increased NG2 immunolabelling with hypertrophy and bushy, ramified appearance of their processes. MIMO2 displayed ameliorative and antioxidative effects in vanadium-induced neurotoxicity in experimental murine species. This is likely the first time MIMO2 is being used in vivo in an animal model.

Bacopa monnieri is an Ayurvedic plant with rising interest in the pharmacological effects of its extract and constituents, including flavonoids, saponins, and triterpenes such as cucurbitacins, betulinic acid, and bacosine. The latter two compounds are isomeric 3-hydroxy lupenoic acids, which vary only in the arrangement of the carboxylic acid group and the methyl group at C-27 and C-28 and the orientation of the hydroxy group at C-3. In this study, we have reinvestigated the contents of betulinic acid and bacosine, respectively, in extracts from various commercially available B. monnieri powders and food supplements. To our surprise, HPLC-ion trap time-of-flight analyses identified only betulinic acid, but not bacosine, in all extracts under study, which was verified by GC-MS, HPLC-ELSD, 1D NMR (1H,13C), and 2D NMR (1H,1H COSY, 1H,13C HMBC, 1H,13C HSQC, 1H,1H NOESY) experiments. Moreover, it turned out that commercially available reference samples of bacosine were structurally identical with betulinic acid.

Pan-assay interference compounds (PAINS) are molecules showing promising but deceptive activities in various biochemical screenings mainly due to unselective interactions with the target. Overall awareness of this problem has been raised recently. Many natural products inherently have PAINS characteristics but are nevertheless uncritically acclaimed as new antiprotozoal lead structures. However, a non-selective mode of action may be the cause of observed activity. This review describes the most common assay-interfering characteristics of antiprotozoal natural products, discusses significant examples from the recent literature and strategies to deal with these promiscuous structures.

Moringa oleifera is reported to be a miracle plant, with positive effects on practically every system in the animal body. The methanolic extract of Moringa oleifera leaves was fractionated using liquid-liquid fractionation, column chromatography and preparative high-performance liquid chromatography (HPLC). Bioassay guided fractionation using Ferric Reducing Antioxidant Power (FRAP) was used to determine the fraction with the highest antioxidative power. Chemical structure was elucidated with nuclear magnetic resonance (NMR) spectroscopy. FRAP showed that the pure compound, butyl p-hydroxyphenyl-acetate (MIMO2) exhibited an antioxidant activity higher than TEMPOL (positive control). Vanadium is a metal, which as a salt has been shown to be a neurotoxicant; and was therefore used to assess the efficacy of MIMO2 in this experiment. HT22 (immortalized mouse hippocampal) cells were used for cell culture. The Comet assay showed a statistically significant reduction (p .05) in DNA damage when 0.25 and 0.5 μM MIMO2 as well as 0.1 and 0.2 mg of the methanolic extract of Moringa oleifera leaves (MO) were used in combination with 200 μM vanadium (sodium metavanadate). Analogously, a reduced formation of superoxide was observed using dihydroethidium (2,7-Diamino-10-ethyl-9-phenyl-9,10-dihydrophenanthridine-DHE) stain after 0.5 μM MIMO2 and 0.063 mg MO were used in combination with vanadium 100 μM. MIMO2 and MO gave a statistically significant (p .05) protective effect against vanadium toxicity on neuronal cells. Further assays may need to be performed to assess the extent of protection that MIMO2 may offer, and also to better understand its mechanisms of action.

Bioassay-guided fractionation of a chloroform extract of Valeriana wallichii (V. wallichii) rhizomes lead to the isolation and identification of caffeic acid bornyl ester (1) as the active component against Leishmania major (L. major) promastigotes (IC50 = 48.8 µM). To investigate the structure-activity relationship (SAR), a library of compounds based on 1 was synthesized and tested in vitro against L. major and L. donovani promastigotes, and L. major amastigotes. Cytotoxicity was determined using a murine J774.1 cell line and bone marrow derived macrophages (BMDM). Some compounds showed antileishmanial activity in the concentration range of pentamidine and miltefosine which are the standard drugs in use. In the L. major amastigote assay compounds 15, 19 and 20 showed good activity with relatively low cytotoxicity against BMDM, resulting in acceptable selectivity indices. Molecules with adjacent phenolic hydroxyl groups exhibited elevated cytotoxicity against murine cell lines J774.1 and BMDM. The Michael system seems not to be essential for antileishmanial activity. Based on the results compound 27 can be regarded as new lead structure for further structure optimization.