title: Neem leaf glycoprotein is nontoxic to physiological functions of Swiss mice and Sprague Dawley rats: histological, biochemical and immunological perspectives.
abstract: We have evaluated the toxicity profile of a unique immunomodulator, neem leaf glycoprotein (NLGP) on different physiological systems of Swiss mice and Sprague Dawley rats. NLGP injection, even in higher doses than effective concentration caused no behavioral changes in animals and no death. NLGP injection increased the body weights of mice slightly without any change in organ weights. NLGP showed no adverse effect on the hematological system. Moreover, little hematostimulation was noticed, as evidenced by increased hemoglobin content, leukocyte count and lymphocyte numbers. Histological assessment of different organs revealed no alterations in the organ microstructure of the NLGP treated mice and rats. Histological normalcy of liver and kidney was further confirmed by the assessment of liver enzymes like alkaline phosphatase, SGOT, SGPT and nephrological products like urea and creatinine. NLGP has no apoptotic effect on immune cells but induces proliferation of mononuclear cells collected from mice and rats. Number of CD4(+), CD8(+) T cells, DX5(+) NK cells, CD11b(+) macrophages and CD11c(+) dendritic cells is upregulated by NLGP without a significant change in CD4(+)CD25(+)Foxp3(+) regulatory T cells. Type 1 cytokines, like IFNγ also increased in serum with a decrease in type 2 cytokines. Total IgG content, especially IgG2a increased in NLGP treated mice. These type 1 directed changes help to create an anti-tumor immune environment that results in the restriction of carcinoma growth in mice. Accumulated evidence strongly suggests the non-toxic nature of NLGP. Thus, it can be recommended for human use in anti-cancer therapy.
authors.affiliation: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, 37 S. P. Mukherjee Road, Kolkata, India.
authors.forename: Atanu
authors.initials: A
authors.lastname: Mallick
authors.forename: Sarbari
authors.initials: S
authors.lastname: Ghosh
authors.forename: Saptak
authors.initials: S
authors.lastname: Banerjee
authors.forename: Sayantani
authors.initials: S
authors.lastname: Majumder
authors.forename: Arnab
authors.initials: A
authors.lastname: Das
authors.forename: Bipasha
authors.initials: B
authors.lastname: Mondal
authors.forename: Subhasis
authors.initials: S
authors.lastname: Barik
authors.forename: Kuntal K
authors.initials: KK
authors.lastname: Goswami
authors.forename: Smarajit
authors.initials: S
authors.lastname: Pal
authors.forename: Subrata
authors.initials: S
authors.lastname: Laskar
authors.forename: Koustav
authors.initials: K
authors.lastname: Sarkar
authors.forename: Anamika
authors.initials: A
authors.lastname: Bose
authors.forename: Rathindranath
authors.initials: R
authors.lastname: Baral
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D031601:Azadirachta; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology* / Q000627:therapeutic use; D007136:Immunoglobulins / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008517:Phytotherapy; D018515:Plant Leaves; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology; D047368:Tumor Burden / Q000187:drug effects; D014508:Urea / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D006023:Glycoproteins; D007136:Immunoglobulins; D007155:Immunologic Factors; D014508:Urea; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase