Nimbolide, a Neem Limonoid, Is a Promising Candidate for the Anticancer Drug Arsenal

Abstract

Nimbolide, a major limonoid constituent of Azadirachta indica, commonly known as neem, has attracted increasing research attention owing to its wide spectrum of pharmacological properties, predominantly anticancer activity. Nimbolide is reported to exert potent antiproliferative effects on a myriad cancer cell lines and chemotherapeutic efficacy in preclinical animal tumor models. The potentiality of nimbolide to circumvent multidrug resistance and aid in targeted protein degradation broaden its utility in enhancing therapeutic modalities and outcome. Accumulating evidence indicates that nimbolide prevents the acquisition of cancer hallmarks such as sustained proliferation, apoptosis evasion, invasion, angiogenesis, metastasis, and inflammation by modulating kinase-driven oncogenic signaling networks. Nimbolide has been demonstrated to abrogate aberrant activation of cellular signaling by influencing the subcellular localization of transcription factors and phosphorylation of kinases in addition to influencing the epigenome. Nimbolide, with its ever-expanding repertoire of molecular targets, is a valuable addition to the anticancer drug arsenal.

The Antimicrobial Potential of the Neem Tree Azadirachta indica

“…The neem tree contains hundreds of compounds (i.e., phytochemicals), many of which have been found to be bioactive and to have diverse utility on their own. Out of the more than 300 unique compounds have been identified within the neem tree, some of the more abundant phytochemicals (e.g., azadirachtin, gedunin, and nimbolide) have already been defined as potential drugs with a wide range of biological activities ( Saleem et al, 2018 ; Braga et al, 2020 ; Nagini et al, 2021 ). The compounds that have been most thoroughly investigated for their individual antimicrobial properties thus far are limonoids, which are compounds that typically consist of four, six-membered rings and one five-membered aromatic ring (i.e., a furanolactone core) and make up one-third of the phytochemicals derived from the neem tree ( Roy and Saraf, 2006 ; Gupta et al, 2017 ).…”

Molecular docking study of GSK‐3β interaction with nomilin, kihadanin B, and related limonoids and triterpenes with a furyl‐δ‐lactone core

“…(Figure 5). [72,73] This latter compound has been previously shown to be able to bind to the kinase domaine of GSK-3β (and to other kinases) increasing the activity of the enzyme and exerting prominent anticancer effects. [74,75] We can consider nimbolide (11) as another reference compound in the limonoid series.…”

Phytochemicals for the Prevention and Treatment of Renal Cell Carcinoma: Preclinical and Clinical Evidence and Molecular Mechanisms

“…Nimbolide (Figure 3), a major limonoid constituent present in the leaves and flowers of neem (Azadirachta indica), has been shown to exhibit potent antiproliferative effects against various cancer cell lines and chemotherapeutic efficacy in animal tumor models [218,219]. In a study performed on 786-O and A-498 RCC cells, nimbolide treatment demonstrated increased cytotoxicity with increased concentrations of up to 6 µM compared to human normal renal tubular cells (HK2 cells), which revealed an absence of increased cytotoxicity for concentrations below 6 µM.…”