Extending the lore of curcumin as dipteran Butyrylcholine esterase (BChE) inhibitor: A holistic molecular interplay assessment.

Since its origin, the emergence of vector-borne infections has taken a toll on incalculable human lives. The use of chemical insecticides is one of the early known methods of vector control and although their use is still a prevalent way to combat insect population sadly the perils of insects related transmission still persists. Most commonly, the existing insecticides face the wrath of getting resisted repeatedly, paying way to develop resilient, efficient, and cost-effective natural insecticides. In this study, computational screening was performed using homology modelling, E-pharmacophore feature mapping, molecular docking, Density Function Theory (DFT) assessment, Molecular mechanics generalized Born surface area (MM-GBSA) based binding free energy calculations and Molecular Dynamics (MD) simulation to identify a potential lead phytochemical out of a manually curated library from published literature. The protein target used under this study is insect Butyrylcholine esterase (BChE). Additionally, in vitro insect (Aedes aegypti) BChE inhibition assay was also performed with the top phytochemical identified from in silico assessments. Our research highlights that curcumin leads to inhibition of enzyme BChE of Ae. aegypti. The identified mode of action of curcumin as an insect BChE inhibitor indicates the possibility of its use as an environment friendly and natural futuristic insecticide.

Curcumin improves insulin sensitivity and increases energy expenditure in high-fat-diet-induced obese mice associated with activation of FNDC5/irisin.

OBJECTIVE: Curcumin (Cur) has a beneficial role in preventing metabolic dysfunctions; however, the underlying mechanism are not yet fully understood. The aim of this study was to evaluate whether the beneficial metabolic effects of curcumin are associated with the regulation of energy metabolism and activation of fibronectin type 3 domain-containing protein 5 (FNDC5)/irisin. METHODS: We used cellular and molecular techniques to investigate the effects of Cur on C57 BL/6 mice that were fed either a control diet or a high-fat diet (HFD) with or without 0.2% Cur for 10 wk. Factors involved in energy metabolism, inflammatory responses, and insulin signaling, as well as the involvement of FNDC5/irisin pathway, were assessed. RESULTS: Cur alleviated adiposity and suppressed inflammatory response in white adipose tissue (WAT) of HFD mice. Meanwhile, Cur administration increased plasma irisin concentration and improved insulin sensitivity of HFD mice. Cur increased the oxygen consumption and heat production and reduced respiratory exchange ratio (RES) in HFD mice, which were accompanied by the enhancement of metabolic activity in brown fat and inguinal WAT. Additionally, the improvement of basal metabolic rate by Cur may be partly regulated by the FNDC5/ p38 mitogen-activated protein kinase (p38 MAPK)/extracellular signal-related kinase (ERK) 1/2 pathway. CONCLUSIONS: These findings demonstrated that dietary Cur alleviated diet-induced adiposity by improving insulin sensitivity and whole body energy metabolism via the FNDC5/p38 MAPK/ERK pathways.

Combining in vitro digestion model with cell culture model: Assessment of encapsulation and delivery of curcumin in milled starch particle stabilized Pickering emulsions.

To investigate the encapsulation and oral delivery efficiency of milled starch particles stabilized Pickering emulsions for lipophilic bioactive compounds, in vitro digestion model coupled with Caco-2 cells models were used. Physicochemical and biological properties of curcumin encapsulated Pickering emulsions were analyzed regarding to emulsion structure, curcumin retention, in vitro digestion, in vitro anti-proliferate ability and cellular uptake. Milled starch particles stabilized Pickering emulsion system was able to protect curcumin against harsh gastric conditions. Around 80% of the encapsulated curcumin was retained after 2 h of simulated gastric digestion. By being encapsulated in Pickering emulsion, the bioaccessibility of curcumin was increased from 11% for curcumin in bulk oil phase to 28% under simulated intestinal digestion process. The resulting curcumin-loaded micelle phase from digested emulsion exhibited significant anti-cancer ability and enhanced cellular uptake. This research provides an exploratory study on the possible future application of milled starch particles stabilized Pickering emulsions as nutraceutical delivery vehicles in the creation of novel functional foods.

Assessment of dynamic bioaccessibility of curcumin encapsulated in milled starch particle stabilized Pickering emulsions using TNO's gastrointestinal model.

Pickering emulsions stabilized by milled starch particles have been developed as a novel food-grade formulation to enhance the bioaccessibility of poorly soluble bioactive compounds (i.e., curcumin) by controlling the digestion of lipids in the human gastrointestinal (GI) tract. The dynamic bioaccessibilities of curcumin with and without encapsulation in the Pickering emulsion were evaluated using the dynamic TNO's gastrointestinal (TIM-1) model. For comparison, their digestion profiles were also studied using the in vitro pH-stat lipolysis model. With the combination of two in vitro models, the effect of the milled starch particle stabilized Pickering emulsions on the bioaccessibility of curcumin was fully revealed. There are large differences between the bioaccessibility values of curcumin samples obtained by these two models. Simulated small intestinal lipolysis in the pH-stat model revealed that the bioaccessibility of curcumin encapsulated in the Pickering emulsion was 27.6%, which was larger than 22.1% for free curcumin suspended in the bulk oil phase. The bioaccessibility of curcumin was 50.7% in the emulsion system and 7.8% in the bulk oil when using the TIM-1 model, which simulated the digestion conditions of the entire human GI tract. The digestion mechanism of the milled starch particle stabilized Pickering emulsions in the upper GI tract was well elucidated by the TIM-1 model. The gradual release and improved dissolution profile of the milled starch particle stabilized Pickering emulsions highlighted their potential as delivery systems for lipophilic bioactive compounds.