Investigation of the chemopreventive potential of neem leaf subfractions in the hamster buccal pouch model and phytochemical characterization

• Published in: European journal of medicinal chemistry 2012-10, Vol.56, p.271-281
• Main Authors: Manikandan, Palrasu, Ramalingam, Senthil Murugan, Vinothini, Govindarajah, Ramamurthi, Vidya Priyadarsini, Singh, Inder Pal, Anandan, Rangasamy, Gopalakrishnan, Mannathusamy, Nagini, Siddavaram
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Azadirachta - chemistry; Azadirachta indica; Biological and medical sciences; Body Weight - drug effects; Cell Proliferation - drug effects; Chemistry, Physical; Chemoprevention; Cricetinae; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Enzymes - metabolism; Medical sciences; Miscellaneous; Molecular Structure; Neoplasms - drug therapy; Neoplasms - pathology; Nuclear factor-κB; Pharmacology. Drug treatments; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plant Leaves - chemistry; Signal Transduction - drug effects; Structure-Activity Relationship; Xenobiotic-metabolizing enzymes
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2012.08.008

Chemoprevention by medicinal plants has evolved as a practical strategy to control the incidence of cancer. Azadirachta indica (neem) containing various bioactive components is a promising candidate for chemoprevention. The present study was undertaken to evaluate the chemopreventive efficacy of the bioactive subfractions ethyl acetate chloroform insoluble fraction (ECIF) and the methanol ethyl acetate insoluble fraction (MEIF) following activity-guided fractionation of neem leaf extract. Analysis of the mechanism of chemoprevention revealed multitargeted mode of action that involved modulation of xenobiotic-metabolizing enzymes, inhibition of cell proliferation, induction of mitochondrial apoptosis, and abrogation of NF-κB signaling. HP-TLC, GC-MS and LC-MS analyses indicated the presence of several polar phytochemical entities in the neem leaf subfractions that might be responsible for their potent chemopreventive efficacy. Chemoprevention by medicinal plants has evolved as a practical strategy to control the incidence of cancer. The chemopreventive potential of neem leaf subfractions may be attributed to the constituent phytochemicals. [Display omitted] ► Neem leaf subfractions modulate XMEs, cell proliferation, apoptosis, and NF-κB signaling. ► ECIF contains nimbolide, nimonol,6-deacetylnimbinene. ► MEIF contains nimbolide, nimonol, 6-deacetyl nimbinene and quercetin.