gedunin and nimbolide

For centuries, agents derived from natural sources (mother nature), especially plants have been the primary source of medicine. Neem, also referred to as Azadirachta indica is one such plant that has been so named because it provides freedom from all diseases, and used for thousands of years in Indian and African continents. Different parts of the plant including flowers, leaves, seeds and bark have been used to treat both acute and chronic human diseases; and used as insecticide; antimicrobial, larvicidal, antimalarial, antibacterial, antiviral, and spermicidal.. What is there in neem and how it manifests its wide variety of effects is the focus of this review. How neem and its constituents modulate various cellular pathways is discussed. The animal and human studies carried out with neem and its constituents is also discussed.. Over 1000 research articles published on neem has uncovered over 300 structurally diverse constituents, one third of which are limonoids including nimbolide, azadarachtin, and gedunin. These agents manifest their effects by modulating multiple cell signaling pathways.

Topics: Animals; Azadirachta; Clinical Trials as Topic; Flowers; Humans; Limonins; Molecular Structure; Phytochemicals; Plant Bark; Plant Extracts; Plant Leaves; Seeds

In vitro evaluation of chemotherapeutic agents against Babesia and Theileria parasites has become routine, and the effectiveness of these chemicals is usually determined by comparing the parasitemia dynamics of untreated and treated parasites. Although microscopy is widely used to calculate parasitemia, several disadvantages are associated with this technique. The present study evaluated a fluorescence-based method using SYBR green I stain (SG I) to screen antibabesial agents in in vitro cultures of Babesia bovis. The linearity between relative fluorescence units (RFU) and parasitemia was found to be well correlated with a 0.9944 goodness-of-fit (r(2)) value. Subsequently, 50% inhibitory concentration (IC50) values were calculated for 3 antiprotozoan agents, diminazene aceturate, nimbolide, and gedunin, by this method. For diminazene aceturate and nimbolide, the IC(50)s determined by the fluorescence-based method (408 nM and 8.13 μM, respectively) and microscopy (400.3 nM and 9.4 μM, respectively) were in agreement. Furthermore, the IC50 of gedunin determined by the fluorescence-based method (19 μM) was similar to the recently described microscopy-based value (21.7 μM) for B. bovis. Additionally, the Z' factor (0.80 to 0.90), signal-to-noise (S/N) ratio (44.15 to 87.64), coefficient of variation at the maximum signal (%CVmax) (0.50 to 2.85), and coefficient of variation at the minimum signal (%CVmin) (1.23 to 2.21) calculated for the fluorescence method using diminazene aceturate were comparable to those previously determined in malaria research for this assay. These findings suggest that the fluorescence-based method might be useful for antibabesial drug screening and may have potential to be developed into a high-throughput screening (HTS) assay.

Topics: Antiprotozoal Agents; Babesia bovis; Benzothiazoles; Diamines; Diminazene; Fluorescence; Fluorescent Dyes; High-Throughput Screening Assays; Inhibitory Concentration 50; Limonins; Organic Chemicals; Parasitic Sensitivity Tests; Quinolines; Signal-To-Noise Ratio; Spectrometry, Fluorescence