Nyctanthes arbor-tristis L.: Perspective of phytochemical-based inhibition of fatty acid biosynthesis in Mycobacterium tuberculosis

Nyctanthes arbor-tristis L. contains various phytochemicals with tremendous potential to fight against different infections. However, the effect of these phytochemicals on Mycobacterium tuberculosis is yet unknown. Treatment of multi-drug resistance (MDR) and extensively drug-resistant (XDR) strains of the tuberculosis bacterium are still challenging. Therefore, there is an urgent need to overcome this problem. The present review focuses on the potential action of the hypolipidemic phytochemicals obtained from N. arbor-tristis on the growth and survival of M. tuberculosis in the human host. The extracts from different parts of this plant are hypolipidemic by various established mechanisms. Phytochemicals like iridoids and flavonoids from plant origin exhibit a high capacity to regulate cholesterol and fatty acid biosynthesis in vivo. The hypolipidemic properties of N. arbor-tristis-derived extracts are probably due to the presence of phytochemicals such as iridoids, flavonoids, etc. It may regulate fatty acid biosynthesis in M. tuberculosis by targeting bacterial fatty acid synthase enzyme. Additionally, these phytochemicals also inhibit cholesterol biosynthesis in the host by interrupting the function of HMG-CoA reductase. M. tuberculosis is an intracellular pathogen. It is also established fact as on date that entry of tuberculosis bacterium in the macrophage is macrophage membrane cholesterol-dependent. Host cholesterol is also otherwise necessary by multiple mechanisms for the pathogenesis of tuberculosis. Based on the above facts, we believe that N. arbor-tristis derived phytochemicals can act both on the tuberculosis bacterium and on the host for prevention and cure of tuberculosis

Cutaneous Epithelial to Mesenchymal Transition Activator ZEB1 Regulates Wound Angiogenesis and Closure in a Glycemic Status–Dependent Manner

Epithelial to mesenchymal transition (EMT) and wound vascularization are two critical interrelated processes that enable cutaneous wound healing. Zinc finger E-box binding homeobox 1 (ZEB1), primarily studied in the context of tumor biology, is a potent EMT activator. ZEB1 is also known to contribute to endothelial cell survival as well as stimulate tumor angiogenesis. The role of ZEB1 in cutaneous wounds was assessed using Zeb1+/− mice, as Zeb1−/− mice are not viable. Quantitative stable isotope labeling by amino acids in cell culture (SILAC) proteomics was used to elucidate the effect of elevated ZEB1, as noted during hyperglycemia. Under different glycemic conditions, ZEB1 binding to E-cadherin promoter was investigated using chromatin immunoprecipitation. Cutaneous wounding resulted in loss of epithelial marker E-cadherin with concomitant gain of ZEB1. The dominant proteins downregulated after ZEB1 overexpression functionally represented adherens junction pathway. Zeb1+/− mice exhibited compromised wound closure complicated by defective EMT and poor wound angiogenesis. Under hyperglycemic conditions, ZEB1 lost its ability to bind E-cadherin promoter. Keratinocyte E-cadherin, thus upregulated, resisted EMT required for wound healing. Diabetic wound healing was improved in ZEB+/− as well as in db/db mice subjected to ZEB1 knockdown. This work recognizes ZEB1 as a key regulator of cutaneous wound healing that is of particular relevance to diabetic wound complication