azadirachtin and nimbin

Azadirachta indica L. is a multipurpose medicinal tree of family Meliaceae. It occurs in tropical and semitropical regions of the world. Different parts of this miraculous tree are used to treat pyrexia, headache, ulcer, respiratory disorders, cancer, diabetes, leprosy, malaria, dengue, chicken pox, and dermal complications. The tree is popular for its pharmacological attributes such as hypolipidemic, antifertility, microbicidal, antidiabetic, anti-inflammatory, hepatoprotective, antipyretic, hypoglycemic, insecticidal, nematicidal, antiulcer, antioxidant, neuroprotective, cardioprotective, and antileishmaniasis properties. A. indica is also rich in various phytochemicals for pharmaceuticals such as alkaloids, steroids, flavonoids, terpenoids, fatty acids, and carbohydrates. The fungicidal potential of the tree is due to the presence of azadirachtin and nimbin. Herein, we have compiled a comprehensive review of phytochemical profile, pharmacological attributes, and therapeutic prospective of this multipurpose tree.

Topics: Azadirachta; Humans; Limonins; Neoplasms; Phytochemicals; Phytotherapy; Plant Extracts; Prospective Studies; Terpenes

One new compound, 2H, 3H-cyclopent[b] furo [2',3':4,5] naphtho [2,4-d] heptlactone-[3,7] furan-6aceticacid, 3-(acetyloxy)-8-(3-furyl)-2a, 4a, 4b, 4c,5,5a, 6, 6a, 8, 9,9a, 10a,10b-13 hydrogen-2a,5a,6a,5-tetramethyl-3-[[(2E)-2-methyl-1-oxo-2-butenyl]oxy]-methyl ester, named azadirachta R (1), along with 10 known ones, Azadirachta A, AZ-B, AZ-D, AZ-H, AZ-I, nimbin, deacetylnimbin, salannin, deacetylsalannin and azadiradione were isolated from the crude extracts of neem (Azadirachta indica A. Juss) seeds, which were determined by UV, IR, HR-ESI-MS and NMR data analyses. According to the in vitro antibacterial activity experimental results, this compound showed good antibacterial activity to two bacteria, the minimum inhibitory concentration and the minimum bactericidal concentration of compound 1 to two kinds of bacteria are 50 and 25 mg/L, respectively, which were determined by resazurin colour-micro-dilution method. The experimental results provide a theoretical basis for the comprehensive utilisation of azadirachtin compounds in the future.

Topics: Anti-Bacterial Agents; Azadirachta; Drug Evaluation, Preclinical; Limonene; Limonins; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Molecular Structure; Plant Extracts; Seeds; Triterpenes

Azadirachta indica, known as neem tree and traditionally called "nature's drug store" makes part of several African pharmacopeias and is widely used for the preparation of homemade remedies and commercial preparations against various illnesses, including malaria. Employing a bio-guided fractionation approach, molecules obtained from A. indica ripe and green fruit kernels were tested for activity against early sporogonic stages of Plasmodium berghei, the parasite stages that develop in the mosquito mid gut after an infective blood meal. The limonoid deacetylnimbin (3) was identified as one the most active compounds of the extract, with a considerably higher activity compared to that of the close analogue nimbin (2). Pure deacetylnimbin (3) appeared to interfere with transmissible Plasmodium stages at a similar potency as azadirachtin A. Considering its higher thermal and chemical stability, deacetylnimbin could represent a suitable alternative to azadirachtin A for the preparation of transmission blocking antimalarials.

Topics: Animals; Antimalarials; Azadirachta; Female; Limonins; Mice, Inbred BALB C; Molecular Structure; Plasmodium berghei; Seeds

Thirty-five limonoids, including 15 of the azadiradione type (1-15), five of the gedunin type (16-20), four of the azadirachtin type (21-24), nine of the nimbin type (25-33), and two degraded limonoids (34, 35), isolated from Azadirachta indica seed extracts, were evaluated for their cytotoxic activities against five human cancer cell lines. Seven compounds (3, 6, 7, 16, 18, 28, and 29) exhibited cytotoxic activity against one or more cell lines. Among these compounds, 7-deacetyl-7-benzoylepoxyazadiradione (7), 7-deacetyl-7-benzoylgeduin (18), and 28-deoxonimbolide (28) exhibited potent cytotoxic activity against HL60 leukemia cells with IC(50) values in the range 2.7-3.1 μM. Compounds 7, 18, and 28 induced early apoptosis in HL60 cells, observed by flow cytometry. Western blot analysis showed that compounds 7, 18, and 28 activated caspases-3, -8, and -9 in HL60 cells. This suggested that compounds 7, 18, and 28 induced apoptotic cell death in HL60 cells via both the mitochondrial- and the death receptor-mediated pathways. Futhermore, compound 7 was shown to possess high selective cytotoxicity for leukemia cells since it exhibited only weak cytotoxicity against a normal lymphocyte cell line (RPMI 1788).

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Azadirachta; Drug Screening Assays, Antitumor; HL-60 Cells; Humans; Limonins; Lymphocytes; Mitochondria; Molecular Structure; Receptors, Death Domain; Seeds

The degradation of the main azadirachtoids on tomatoes was studied after greenhouse treatment. These experiments were carried out at 1 and 5x the concentration recommended by the manufacturer. In all experiments the deposition of azadirachtin A (AZA-A) was below the maximum residue level (MRL). Even if at the highest dose, AZA-A half-life time calculated as pseudo first order kinetic was 1.2 days in agreement with the recommended preharvest interval (PHI) of 3 days. Experiments with a model system showed that sunlight photodegradation is the main factor influencing the rate of disappearance of AZA-A after greenhouse treatment while tomato epicuticular waxes doubled the photodegradation rate of AZA-A in a commercial formulation.

Topics: Chromatography, High Pressure Liquid; Food Technology; Half-Life; Insecticides; Kinetics; Limonene; Limonins; Photolysis; Solanum lycopersicum; Spectrometry, Mass, Electrospray Ionization; Sunlight; Triterpenes

Azadirachtoids were determined by liquid chromatography/mass spectrometry (LC/MS) in five methanolic seed extracts of the neem tree and in a commercial formulation. On average, seed extracts contain azadirachtin A (10.9%), azadirachtin B (3.5%), nimbin (10.4%), and large quantities of salannin (19.0%). The composition of the commercial formulations may present different azadirachtoids contents depending on the natural extracts used in the preparation. Because these compounds may also show insecticide activity, the efficacy on field of these formulations may be very different. Photodegradation of pure azadirachtoids was also studied. Azadirachtins and related compounds are very sensitive to sunlight, degrading rapidly, with half-lives of the order of 11.3 h for azadirachtin A and 5.5 h for azadirachtin B and few minutes for the other limonoids compounds studied. The residues of azadirachtins and the main constituents, e.g., salannin, nimbin, deacetylnimbin, and deacetylsalannin, of the neem seed extract were determined on strawberries after field treatment using two different formulations. This residue study on strawberry was carried out to assess not only the azadirachtin content but also the main azadirachtoids contents. Three days after field application at five times the dose recommended by the manufacturer, residues of azadirachtin A and B were 0.03 and 0.01 mg/kg, respectively, while residues of salannin (LOQ 0.01 mg/kg) and nimbin (LOQ 0.5 mg/kg) were not detectable.

Topics: Azadirachta; Fragaria; Fruit; Half-Life; Limonene; Limonins; Plant Extracts; Sunlight; Triterpenes

A range of cultured cells of invertebrate and vertebrate origin was grown in the presence of a number of phytochemical pesticides to test the effect of the latter on cell proliferation. The main observation was that azadirachtin was a potent inhibitor of insect cell replication, with an EC50 of 1.5 x 10(10) M against Spodoptera cells and of 6.3 x 10(9) M against Aedes albopictus cells, whilst affecting mammalian cells only at high concentrations (> 10(-4) M). As expected, the other phytochemical pesticides, except for rotenone, had little effect on the growth of the cultured cells. Rotenone was highly effective in inhibiting the growth of insect cells (EC50:10(-8) M) but slightly less toxic towards mammalian cells (EC50:2 x 10(-7) M). Neem terpenoids other than azadirachtin and those very similar in structure significantly inhibited growth of the cell cultures, but to a lesser degree. The major neem seed terpenoids, nimbin and salannin, for example, inhibited insect cell growth by 23% and 15%, respectively.

Topics: Animals; Cell Division; Cell Line; Cells, Cultured; Chrysanthemum cinerariifolium; Diterpenes; Dose-Response Relationship, Drug; Humans; Insecta; Insecticides; Invertebrates; Limonene; Limonins; Molecular Structure; Rotenone; Terpenes; Triterpenes; Tumor Cells, Cultured

A simple and rapid method involving solid phase extraction and liquid chromatography for the determination of azadirachtin-A and -B, nimbin and salannin at nanogram levels in neem oil samples is presented. The neem oil samples are defatted and the compounds of interest extracted by mixing the sample with hexane and passing the hexane solution through a graphitised carbon black column. After washing the column with 2 ml of hexane, azadirachtin-A and -B, nimbin and salannin are eluted with 5 ml of acetonitrile and quantified using HPLC with UV detection. The recoveries of azadirachtin-A and -B, nimbin and salannin in fortified oil samples were 97.4-104.7%. The upper limit of quantification is up to 100 micrograms ml-1 without any additional clean-up and with little interference from lipids during the analysis by HPLC. The method was successfully applied to various neem oil samples collected from different locations in India.

Topics: Antiviral Agents; Diterpenes; Enzyme Inhibitors; Glycerides; Humans; Insect Repellents; Insecticides; Limonene; Limonins; Terpenes; Triterpenes

The effects of azadirachtin, salannin, nimbin, and 6-desacetylnimbin on ecdysone 20-monooxygenase (E-20-M) activity were examined in three insect species. Homogenates of wandering stage third instar larvae of Drosophila melanogaster, or abdomens from adult female Aedes aegypti, or fat body or midgut from fifth instar larvae of Manduca sexta were incubated with radiolabeled ecdysone and increasing concentrations (from 1 x 10(-8) to 1 x 10(-3) M) of the four compounds isolated from seed kernels of the neem tree, Azadirachta indica. All four neem tree compounds were found to inhibit, in a dose-dependent fashion, the E-20-M activity in three insect species. The concentration of these compounds required to elicit a 50% inhibition of this steroid hydroxylase activity in the three insect species examined ranged from approximately 2 x 10(-5) to 1 x 10(-3).

Topics: Aedes; Animals; Aryl Hydrocarbon Hydroxylases; Diterpenes; Drosophila melanogaster; Enzyme Inhibitors; Female; Insecticides; Limonene; Limonins; Manduca; Steroid Hydroxylases; Triterpenes