Anti-inflammatory, pro-apoptotic, and anti-proliferative effects of a methanolic neem (Azadirachta indica) leaf extract are mediated via modulation of the nuclear factor-κB pathway

Abstract

Azadirachta indica (neem tree) is used in traditional Indian medicine for its pharmacological properties including cancer prevention and treatment. Here, we studied a neem extract's anti-inflammatory potential via the nuclear factor-jB (NF-jB) signaling pathway, linked to cancer, inflammation, and apoptosis. Cultured human leukemia cells were treated with a methanolic neem leaf extract with or without tumor necrosis factor (TNF)-a stimulation. Inhibition of NF-jB activity was demonstrated by luciferase assay and electrophoretic mobility shift assay (EMSA). Inhibition of viability by neem extracts was assessed by luminescent assays. Western blot analysis allowed assessing the inhibitory effect of the neem extract on TNF-a-induced degradation of inhibitor of jB (IjB) and nuclear translocation of the NF-jB p50/p65 heterodimer. Inhibition of IjB kinase (IKK) activity was shown as well as the effect of neem extract on the induction of apoptotic cell death mechanisms by nuclear fragmentation analysis and flow cytometry analysis. In conclusion, our data provide evidence for a strong effect of the neem extract on proinflammatory cell signaling and apoptotic cell death mechanisms, contributing to a better understanding of the mechanisms triggered by Azadirachta indica.

Comparative Study on in-Vivo Anti-Inflammatory Potential From Leaves of Methanol and Chloroform Extracts of Azadirachta Indica A. Juss and Justicia Adhatoda in Nepal

“…Similar studies conducted before showed potent anti-inflammatory activity of methanol and chloroform extract of both plants [26][27][28] . …”

Prevention of TLR9 Pathway in Warm Ischemia in Porcine Donor Liver after Cardiac Death

“…It is well known that NF-κB is constantly functional in the cell as a transcription factor protein [18]. In resting cells, NF-κB and IκB form an inactive cytoplasm complex.…”

Anti-Inflammatory and Anticancer Drugs from Nature

“…Recently, we provided evidence that nature provides excellent inhibitors of NF-jB: we showed that curcumin [21][22][23]; b-lapachone and emodin, sanguinarine, and capsaicin [24]; kawains [25]; naphtopyrones [26]; cardenolides [27,28]; heteronemin [29]; polyketide derivatives [30]; chalcones [31,32]; and neem leaf extract [33] efficiently inhibit NF-jB cell signaling pathways. Recent reports demonstrate that this is a very active field of research worldwide [6,22,[34][35][36][37][38][39].…”