Prophylactic Dose of Neem (Azadirachta indica) Leaf Preparation Restricting Murine Tumor Growth is Nontoxic,Hematostimulatory and Immunostimulatory

Significant restriction of growth of Ehrlich's carcinoma was observed following prophylactic treatment on Swiss albino mice with neem leaf preparation (NLP-1 unit) once weekly for four weeks. Toxic effects of this particular dose (1 unit), along with 0.5 unit and 2 units of NLP doses, were evaluated on different murine physiological systems. One hundred percent of mice could tolerate 4 injections of 0.5 and 1 unit NLP doses. Body weight, different organ-body weight ratios and physical behavior of treated mice remained completely unchanged during treatment with different NLP doses. All of these NLP doses were observed to stimulate hematological systems as evidenced by the increase in total count of RBC, WBC and platelets and hemoglobin percentage. As histological changes as well as elevation in serum alkaline phosphatase, SGOT, SGPT were not observed in mice treated with three different doses of NLP, the nonhepatotoxic nature of NLP was proved. The level of serum urea remained unaltered and normal architecture of the cortical and medullary parts of the kidney were also preserved after NLP treatment. Increased antibody production against B16 melanoma antigen was detected in mice immunized with 0.5 unit and 1 unit of NLP. Number of splenic T lymphocytes (CD4+ and CD8+) and NK cells were also observed to be increased in mice injected with 0.5 unit and 1 unit of NLP. However, NLP dose of 2 units could not exhibit such immunostimulatory changes; NLP mediated immunostimulation was correlated well with the growth restriction of murine carcinoma. In other words, tumor growth restriction was observed only when mice were injected with immunostimulatory doses of NLP (0.5 unit and 1 unit).     

Azadirachta indica Leaf Extract as Green Corrosion Inhibitor for Reinforced Concrete Structures: Corrosion Effectiveness against Commercial Corrosion Inhibitors and Concrete Integrity

The construction industry has extensively demanded novel green inhibition strategies for the conservation and protection of carbon steel-reinforced concrete structures. For the first time, the effect of Azadirachta indica leaf extract (Neem) as a potential corrosion inhibitor of carbon steel in reinforced concrete under corrosion in saline simulated media was evaluated. To assess the corrosion inhibition behavior of the Neem natural organic extract, three inorganic commercial inhibitors were tested to compare following the criteria established by Stratful for half-cell potential under a simulated chloride environment. Moreover, the effect of concrete integrity by the Neem treatment was recorded after different temperature conditions, slump, weight alteration, air content, compressive strength, and chloride-ions penetration. The results suggested that the Neem treatments did not alter the concrete integrity and the physicochemical parameters. We reached a promoted long-term corrosion protection of 95% after 182 days of evaluation. Thus far, our current results open up a new promising “green” road to the conservation of carbon steel in reinforced concrete for the construction industry.     

Efficacy of crude neem seed kernel extracts against natural infestation of Sarcoptes scabiei var. ovis

This study was aimed to evaluate the efficacy of crude aqueous-methanol and aqueous extracts of neem (Azadirachta indica) seed kernel against sarcoptic mange of sheep. Crude aqueous-methanol (AME) and aqueous extracts (AE) of neem seed kernel (NSK) were prepared and formulated as 10% and 20% ointments (w/w), using Vaseline as vehicle. Forty-two lambs of Pak Karakul breed, having natural infection of sarcoptic mange were divided into seven experimental groups. Skin scrapings and clinical examination were carried out at scheduled intervals after treatment. Ivermectin (positive control) completely cleared infesting mites from animals after 10 days and 20% AME after 16 days. While, clinical mange was completely cured after 16 and 20 days with ivermectin and 20% AME, respectively, under field conditions. Only the higher concentration (20% AME) of NSK extracts completely cured the clinical mange, suggesting a dose-dependent response. Our results consolidate the belief that use of folk remedies can provide an effective and economic way of combating sarcoptic mange in sheep.     

Neem leaf glycoprotein regulates function of tumor associated M2 macrophages in hypoxic tumor core: Critical role of IL-10/STAT3 signaling

Heterogeneous tumor microenvironment (TME), broadly divided into tumor core and peripheral sub-microenvironments, differentially polarize normal macrophages into a different form known as tumor associated M2 macrophages (M2TAMs) to promote tumor growth. In view of the extensive immune-editing role of NLGP, here, we have observed that NLGP is effective to convert M2TAMs (CD11b⁺F4/80^high) to M1 (CD11b⁺F4/80^low) more prominently in tumor core, along with downregulation of other M2 associated markers, like, ManR, Ym1, Fizz1. High IL-10:IL-12 ratio at tumor core was downregulated in NLGP treated melanoma bearing mice. Decrease in IL-10 by NLGP is again associated with the decrease in hypoxia, as indicated by prominent downregulation of HIF1α and VEGF, particularly at tumor core. Macrophages exposed to hypoxic tumor core lysates in vitro exhibited high IL-10, HIF1α and VEGF expression that was significantly downregulated by NLGP. Further evidences suggest M2TAM to M1 conversion by NLGP is associated with STAT3-regulated IL-10 dependent pathway without affecting the IL-4 dependent one. Such TAM modulatory functions of NLGP might help in the restriction of melanoma growth by increasing the proportion of M1 TAMs in tumor core that helps in prevention of tumor relapse and dissemination of the tumor mass.     

Evaluation of Azadirachta indica leaf fractions for in vitro antioxidant potential and in vivo modulation of biomarkers of chemoprevention in the hamster buccal pouch carcinogenesis model

We evaluated the chemopreventive potential of Azadirachta indica (neem) leaf fractions based on in vitro antioxidant assays, and in vivo inhibitory effects on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. In addition we also identified the major constituents in neem leaf fractions by HPLC. Analysis of the free radical scavenging activities and reducing potential of crude ethanolic extract (CEE), ethyl acetate fraction (EAF) and methanolic fraction (MF) of neem leaf revealed a concentration-dependent increase in antioxidant potential that was in the order EAF>MF>CEE. Administration of neem leaf fractions reduced the incidence of DMBA-induced HBP carcinomas at a lower concentration compared to the crude extract. Chemoprevention by neem leaf fractions was associated with modulation of phase I and phase II xenobiotic-metabolising enzymes, lipid and protein oxidation, upregulation of antioxidant defences, inhibition of cell proliferation and angiogenesis, and induction of apoptosis. However, EAF was more effective than MF in terms of antiproliferative and antiangiogenic effects, and expression of CYP isoforms. The greater efficacy of EAF may be due to higher content of constituent phytochemicals as revealed by HPLC analysis. The results of the present study suggest that the antioxidant properties of neem leaf fractions may be responsible for modulating key hallmark capabilities of cancer cells such as cell proliferation, angiogenesis and apoptosis in the HBP carcinogenesis model.     

An antimalarial extract from neem leaves is antiretroviral

An acetone-water neem leaf extract with antimalarial activity was evaluated in vitro at 5 microg/ml for inhibition of adhesion of malaria parasite-infected erythrocytes and cancer cells to endothelial cells, and at 10 microg/ml for protection of lymphocytes against invasion by HIV. The extract was also evaluated in 10 patients with HIV/AIDS at 1000 mg daily for 30 d. The mean binding of infected erythrocytes and cancer cells per endothelial cell was 15 and 11 respectively in the absence of the extract, and 0 and 2 respectively in with the extract. In the absence and presence of the extract, 0% and 75%, respectively, of lymphocytes were protected. In the treated patients, haemoglobin concentration, mean CD4+ cell count and erythrocyte sedimentation rate, which were initially 9.8 g/dl, 126 cells/microl and 90 mm/h respectively, improved to 12.1 g/dl, 241 cells/microl and 49 mm/h. Mean bodyweight and platelet count, initially 57 kg and 328 x 10(3)/mm3 respectively, increased to 60 kg and 359 x 10(3)/mm3. No adverse effects were observed during the study. The extract showed antiretroviral activity with a mechanism of action that may involve inhibition of cytoadhesion. The results may help in the development of novel antiretroviral and antimalarial drugs.     

Neem oil poisoning

Twelve children were admitted with convulsions and altered sensorium following ingestion of locally obtained neem oil. Ten died within 24 hours. Of the six children investigated completely, four showed significant acidosis and all showed significant rise in serum transaminases suggesting liver damage. All had normal CSF values. Liver biopsy done in one showed fatty degeneration.     

Prophylactic dose of neem (Azadirachta indica) leaf preparation restricting murine tumor growth is nontoxic, hematostimulatory and immunostimulatory

Significant restriction of growth of Ehrlich's carcinoma was observed following prophylactic treatment on Swiss albino mice with neem leaf preparation (NLP-1 unit) once weekly for four weeks. Toxic effects of this particular dose (1 unit), along with 0.5 unit and 2 units of NLP doses, were evaluated on different murine physiological systems. One hundred percent of mice could tolerate 4 injections of 0.5 and 1 unit NLP doses. Body weight, different organ-body weight ratios and physical behavior of treated mice remained completely unchanged during treatment with different NLP doses. All of these NLP doses were observed to stimulate hematological systems as evidenced by the increase in total count of RBC, WBC and platelets and hemoglobin percentage. As histological changes as well as elevation in serum alkaline phosphatase, SGOT, SGPT were not observed in mice treated with three different doses of NLP, the nonhepatotoxic nature of NLP was proved. The level of serum urea remained unaltered and normal architecture of the cortical and medullary parts of the kidney were also preserved after NLP treatment. Increased antibody production against B16 melanoma antigen was detected in mice immunized with 0.5 unit and 1 unit of NLP. Number of splenic T lymphocytes (CD4+ and CD8+) and NK cells were also observed to be increased in mice injected with 0.5 unit and 1 unit of NLP. However, NLP dose of 2 units could not exhibit such immunostimulatory changes; NLP mediated immunostimulation was correlated well with the growth restriction of murine carcinoma. In other words, tumor growth restriction was observed only when mice were injected with immunostimulatory doses of NLP (0.5 unit and 1 unit).     

Urea-formaldehyde nanocapsules for the controlled release of diclofenac sodium

Urea-formaldehyde (UF), polymerized in situ in aqueous media, is a rigid polymer that can be used in the controlled release of bioactive molecules. During the process of polymerization, liquid neem seed oil (NSO) was encapsulated at three different loadings, which was then replaced by diclofenac sodium (DS), the presence of which was confirmed by FTIR spectra. The nanocapsules thus prepared were evaluated for percentage loading of the drug, particle size and release characteristics. Thermal analysis and x-ray data were obtained to understand the physical nature of the encapsulated drug. The surface characteristics of the nanocapsules were studied using a scanning electron microscope. Particles in the size range around 500nm were obtained. The percentage loading efficiency of NSO was 90-95, whereas for DS, the loading efficiency was only 50-60%. Complete release of the drug from the matrices occurred in 24h, whereas, at 8h only 60%of the drug was released.