Micro-Vesicles of Moringa oleifera Seeds in Heterozygous Rats for DAT Gene: Effects of Oral Intake on Behavioral Profile and Hematological Parameters.

Previous studies have shown multiple biological properties of Moringa oleifera, a plant native to Africa and Asia. In the present study, potential physiological properties of microvesicles extracted from Moringa oleifera seeds were assessed. For this purpose, we investigated behavioral profile and hematological parameters in a recent rat model characterized by dysregulation in dopamine transporter, a key regulator of dopaminergic system. Experimental design consisted of male Wistar-DAT rats aged between two and four months: wild-type (WT) (n = 5) and heterozygous (DATHET) (n = 4) control groups, which drank tap water; WT (n = 5) and DATHET (n = 6) groups which drank a solution of Moringa microvesicles and water (2: 68 mL per day), which was orally administered for two months. Rats were monitored for spontaneous locomotor activity on a 24/7 basis. In the early lit hours, treated DATHET subjects showed higher locomotor activity, proposing a sleep-delay effect of Moringa. In forced swimming test, WT subjects who took Moringa exhibited more depressive behavior. In DATHET rats, Moringa seemed to potentiate the struggle to find a way out, counteracting an initial panic. Hemoglobin and hematocrit underwent opposite changes in either genotype, supporting the opposite effects on behavioral phenotype observed. Future work is clearly needed to further explore these preliminary profiles.

Effect of microvesicles from Moringa oleifera containing miRNA on proliferation and apoptosis in tumor cell lines.

Human microvesicles are key mediators of cell-cell communication. Exosomes function as microRNA transporters, playing a crucial role in physiological and pathological processes. Plant microvesicles (MVs) display similar features to mammalian exosomes, and these MVs might enhance plant microRNA delivery in mammals. Considering that plant microRNAs have been newly identified as bioactive constituents in medicinal plants, and that their potential role as regulators in mammals has been underlined, in this study, we characterized MVs purified from Moringa oleifera seeds aqueous extract (MOES MVs) and used flow cytometry methods to quantify the ability to deliver their content to host cells. The microRNAs present in MOES MVs were characterized, and through a bioinformatic analysis, specific human apoptosis-related target genes of plant miRNAs were identified. In tumor cell lines, MOES MVs treatment reduced viability, increased apoptosis levels associated with a decrease in B-cell lymphoma 2 protein expression and reduced mitochondrial membrane potential. Interestingly, the effects observed with MOES MVs treatment were comparable to those observed with MOES treatment and transfection with the pool of small RNAs isolated from MOES, used as a control. These results highlight the role of microRNAs transported by MOES MVs as natural bioactive plant compounds that counteract tumorigenesis.

Plant microRNAs from Moringa oleifera Regulate Immune Response and HIV Infection.

Traditional medicine is often chosen due to its affordability, its familiarity with patient's cultural practices, and its wider access to the local community. Plants play an important role in providing indispensable nutrients, while specific small RNAs can regulate human gene expression in a cross-kingdom manner. The aim of the study was to evaluate the effects of plant-enriched purified extract microRNAs from Moringa oleifera seeds (MO) on the immune response and on HIV infection. Bioinformatic analysis shows that plant microRNAs (p-miRs) from MO belonging to 18 conserved families, including p-miR160h, p-miR166, p-miR482b, p-miR159c, p-miR395d, p-miR2118a, p-miR393a, p-miR167f-3p, and p-miR858b are predicted to target with high affinity BCL2, IL2RA, TNF, and VAV1, all these being involved in the cell cycle, apoptosis, immune response and also in the regulation of HIV pathogenesis. The effects of MO p-miRs transfected into HIV+ PBMCs were analyzed and revealed a decrease in viability associated with an increase of apoptosis; an increase of T helper cells expressing Fas and a decrease of intracellular Bcl2 protein expression. Meanwhile no effects were detected in PBMCs from healthy donors. In CD4+ T cells, transfection significantly reduced cell activation and modified the T cell differentiation, thereby decreasing both central and effector memory cells while increasing terminal effector memory cells. Interestingly, the p-miRs transfection induces a reduction of intracellular HIV p24 protein and a reduction of viral DNA integration. Finally, we evaluated the effect of synthetic (mimic) p-miR858b whose sequence is present in the MO p-miR pool and predicted to target VAV1, a protein involved in HIV-Nef binding. This protein plays a pivotal role in T cell antigen receptor (TCR) signaling, so triggering the activation of various pathways. The transfection of HIV+ PBMCs with the synthetic p-miR858b showed a reduced expression of VAV1 and HIV p24 proteins. Overall, our evidence defines putative mechanisms underlying a supplementary benefit of traditional medicine, alongside current antiretroviral therapy, in managing HIV infection in resource-limited settings where MO remains widely available.

Cytotoxic and apoptotic effects of different extracts of Moringa oleifera Lam on lymphoid and monocytoid cells.

Moringa oleifera Lam. (MO) is one of the most well-known and widely distributed species of the Moringaceae family in African communities, and various preparations of M. oleifera are used for the treatment of several diseases. Due to the extensive worldwide use of MO products, and the use of MO aqueous extract in traditional African medicine, the aim of the present study was to investigate the anti-proliferative, cytotoxic and pro-apoptotic activities of different aqueous extracts from leaves and seeds of M. oleifera (MOE), which have been prepared using different protocols, in lymphoid and monocytoid cells. The results of the present study demonstrated the anti-proliferative and pro-apoptotic effects of the aqueous extracts obtained from M. oleifera leaves and seeds on tumour cells; however, not on peripheral blood mononuclear cells (PBMCs) from healthy donors. The pro-apoptotic effect of MO seed aqueous extract (MOE-S) was correlated with decreased B-cell lymphoma 2 (BCL2) and sirtuin-1 (SIRT1) protein expression, which are involved in apoptosis. Considering the effects of plant secondary metabolites on human cells and the role of plant microRNA in cross-kingdom interactions, the presence of secondary metabolites and microRNA in MOE was characterised. In conclusion, M. oleifera aqueous extracts appeared to be able to differentially regulate proliferation and apoptosis in healthy cells and cancer cells, and this ability could be associated with the microRNA present in the extracts. These results highlighted the possible use of MOE as an adjuvant in traditional cancer therapy.