Curcumin, a yellow-colored molecule derived from the rhizome of Curcuma longa, has been identified as the bioactive compound responsible for numerous pharmacological activities of turmeric, including anticancer, antimicrobial, anti-inflammatory, antioxidant, antidiabetic, etc. Nevertheless, the clinical application of curcumin is inadequate due to its low solubility, poor absorption, rapid metabolism and elimination. Advancements in recent research have shown several components and techniques to increase the bioavailability of curcumin. Combining with adjuvants, encapsulating in carriers and formulating in nanoforms, in combination with other bioactive agents, synthetic derivatives and structural analogs of curcumin, have shown increased efficiency and bioavailability, thereby augmenting the range of applications of curcumin. The scope for incorporating biotechnology and nanotechnology in amending the current drawbacks would help in expanding the biomedical applications and clinical efficacy of curcumin. Therefore, in this review, we provide a comprehensive overview of the plethora of therapeutic potentials of curcumin, their drawbacks in efficient clinical applications and the recent advancements in improving curcumin’s bioavailability for effective use in various biomedical applications.

Intestinal epithelial tight junctions (TJs), a dynamically regulated barrier structure composed of occludin and claudin family of proteins, mediate the interaction between the host and the external environment by allowing selective paracellular permeability between the luminal and serosal compartments of the intestine. TJs are highly dynamic structures and can undergo constant architectural remodeling in response to various external stimuli. This is mediated by an array of intracellular signaling pathways that alters TJ protein expression and localization. Dysfunctional regulation of TJ components compromising the barrier homeostasis is an important pathogenic factor for pathological conditions including inflammatory bowel disease (IBD). Previous studies have elucidated the significance of TJ barrier integrity and key regulatory mechanisms through various in vitro and in vivo models. In recent years, considerable efforts have been made to understand the crosstalk between various signaling pathways that regulate formation and disassembly of TJs. This review provides a comprehensive view on the novel mechanisms that regulate the TJ barrier and permeability. We discuss the latest evidence on how ion transport, cytoskeleton and extracellular matrix proteins, signaling pathways, and cell survival mechanism of autophagy regulate intestinal TJ barrier function. We also provide a perspective on the context-specific outcomes of the TJ barrier modulation. The knowledge on the diverse TJ barrier regulatory mechanisms will provide further insights on the relevance of the TJ barrier defects and potential target molecules/pathways for IBD.

Candida albicans is the primary etiological agent associated with the pathogenesis of candidiasis. Unrestricted growth of C. albicans in the oral cavity may lead to oral candidiasis, which can progress to systemic infections in worst scenarios. Biofilm of C. albicans encompasses yeast and hyphal forms, where hyphal formation and yeast to hyphal morphological transitions are contemplated as the key virulence elements. Current clinical repercussions necessitate the identification of therapeutic agent that can limit the biofilm formation and escalating the susceptibility of C. albicans to immune system and conventional antifungals. In the present study, a plant-derived alkaloid molecule, piperine, was investigated for the antibiofilm and antihyphal activities against C. albicans. Piperine demonstrated a concentration-dependent antibiofilm activity without exerting negative impact on growth and metabolic activity. Inhibition in the hyphal development was witnessed through confocal laser-scanning microscopy and scanning electron microscopy. Interestingly, piperine displayed a tremendous potential to inhibit the virulence-associated colony morphologies, such as filamentation and wrinkling. Furthermore, piperine regulated morphological transitions between yeast and hyphal forms by inhibiting hyphal extension and swapping hyphal phase to yeast forms yet under filamentation-inducing circumstances. Remarkably, piperine-challenged C. albicans exhibited low potential for spontaneous antibiofilm resistance development. In addition, piperine effectively reduced in vivo colonization and prolonged survival of C. albicans-infected Caenorhabditis elegans, thereby expounding the distinct antivirulent potential. Transcriptomic analysis revealed piperine significantly downregulating the expression of several biofilm related and hyphal-specific genes (ALS3, HWP1, EFG1, CPH1, etc.). Furthermore, no acute toxicity was observed in the HBECs and nematodes exposed to piperine. Altogether, results from this study reveals the potential of piperine to inhibit biofilm and hyphal morphogenesis, and its in vivo efficacy and innocuous nature to HBECs suggests that piperine may be considered as a potential candidate for the treatment of biofilm-associated C. albicans infection, especially for oral candidiasis.

The effects of two prominent copper oxide nanoparticles (CuO-NP and Cu₂O-NP), with the oxidation state of Cu⁺⁺ (cupric) and Cu⁺ (cuprous), on Candida albicans were evaluated. CuO-NP and Cu₂O-NP were synthesized and characterized by XRD, FESEM, HR-TEM and Zeta potential. At sub-MIC (50 µg ml⁻¹), both cupric and cuprous oxide NPs prevented yeast-to-hyphae switching and wrinkling behaviour in C. albicans. The mechanism for the antifungal action of the two NPs differed; CuO-NP significantly elicited reactive oxygen species, whereas membrane damage was more pronounced with Cu₂O-NP. Real time PCR analysis revealed that CuO-NP suppressed the morphological switching of yeast-to-hyphae by down-regulating cph1, hst7 and ras1 and by up-regulation of the negative regulator tup1. In comparison, Cu₂O-NP resulted in down-regulation of ras1 and up-regulation of the negative regulators nrg1 and tup1. Between the two NPs, CuO exhibited increased antifungal activity due to its stable oxidation state (Cu⁺⁺) and its smaller dimensions compared with Cu₂O-NP.

In the present study, we have explored the interaction of the active components from 10 different medicinal plants of Indian origin that are commonly used for treating cold and respiratory-related disorders, through molecular docking analysis. In the current scenario, COVID-19 patients experience severe respiratory syndromes, hence it is envisaged from our study that these traditional medicines are very likely to provide a favourable effect on COVID-19 infections. The active ingredients identified from these natural products are previously reported for antiviral activities against large group of viruses. Totally 47 bioactives identified from the medicinal plants were investigated against the structural targets of SARS-CoV-2 (Mpro and spike protein) and human ACE2 receptor. The top leads were identified based on interaction energies, number of hydrogen bond and other parameters that explain their potency to inhibit SARS-CoV-2. The bioactive ligands such as Cucurbitacin E, Orientin, Bis-andrographolide, Cucurbitacin B, Isocucurbitacin B, Vitexin, Berberine, Bryonolic acid, Piperine and Magnoflorine targeted the hotspot residues of SARS-CoV-2 main protease. In fact, this protease enzyme has an essential role in mediating the viral replication and therefore compounds targeting this key enzyme are expected to block the viral replication and transcription. The top scoring conformations identified through docking analysis were further demonstrated with molecular dynamics simulation. Besides, the stability of the conformation was studied in detail by investigating the binding free energy using MM-PBSA method. Overall, the study emphasized that the proposed hit Cucurbitacin E and orientin could serve as a promising scaffold for developing anti-COVID-19 drug. Communicated by Ramaswamy H. Sarma