NRF2 Activation by Nitrogen Heterocycles: A Review

Several nitrogen heterocyclic analogues have been applied to clinical practice, and about 75% of drugs approved by the FDA contain at least a heterocyclic moiety. Thus, nitrogen heterocycles are beneficial scaffolds that occupy a central position in the development of new drugs. The fact that certain nitrogen heterocyclic compounds significantly activate the NRF2/ARE signaling pathway and upregulate the expression of NRF2-dependent genes, especially HO-1 and NQO1, underscores the need to study the roles and pharmacological effects of N-based heterocyclic moieties in NRF2 activation. Furthermore, nitrogen heterocycles exhibit significant antioxidant and anti-inflammatory activities. NRF2-activating molecules have been of tremendous research interest in recent times due to their therapeutic roles in neuroinflammation and oxidative stress-mediated diseases. A comprehensive review of the NRF2-inducing activities of N-based heterocycles and their derivatives will broaden their therapeutic prospects in a wide range of diseases. Thus, the present review, as the first of its kind, provides an overview of the roles and effects of nitrogen heterocyclic moieties in the activation of the NRF2 signaling pathway underpinning their antioxidant and anti-inflammatory actions in several diseases, their pharmacological properties and structural–activity relationship are also discussed with the aim of making new discoveries that will stimulate innovative research in this area

Restorative effects of ethanolic leaf extract of Datura stramonium against methotrexate-induced hematological impairments

AbstractOne of the prominent complications observed in those undergoing treatment with methotrexate (MTX) is hematological profile alterations which could culminate in severe anemia. In this study, we assessed the hematological profile indices in MXT-treated rats and the effect of leaf extract of Datura stramonium (LEDS) supplementation in MXT-treated rats. Ethanol (98%) was the solvent used in extraction. Animals were divided at random into four groups. Animals in group 1 received normal saline (5 mg/kg) orally and feeding was limitless and did not receive MXT. Animals in group 2 were given LEDS orally (200 mg/kg body weight) for 21 days while group 3 received 20 mg/kg body weight (bw) of MXT on day 18 via the intra-peritoneum without LEDS. Rats in group 4 were given the extract (200 mg/kg bw) and also injected with 20 mg/kg bw of MXT on day 18 of the study via the intra-peritoneum. Serum levels of hemoglobin, red blood cells, packed cell volume, total white blood cells, neutrophils, lymphocytes, and platelets were determined. Rats treated with MXT had notable depletion in hemoglobin, red blood cells, packed cell volume, total white blood cells, neutrophils, and platelets, unlike the control group. Interestingly, LEDS supplementation markedly restored the altered hematological profiles. MXT injection caused hematological dysfunction while co-supplementation with LEDS restored the impaired hematological indices. Therefore, LEDS could be a promising tool in arresting hematological dysfunctions accompanying MXT chemotherapy. However, we advocate for further prospective scrutiny