Atherosclerosis, a chronic inflammatory disease defined by plaque formation in artery walls, is still a significant cause of cardiovascular morbidity and mortality globally. Despite advancements in conventional medicines, the search for natural substances with several therapeutic applications continues. Curcumin, a polyphenol produced from Curcuma longa, has emerged as a promising anti-atherosclerosis treatment due to its powerful anti-inflammatory, antioxidant, lipid-modulating, and endothelial-protective characteristics. This article explores how curcumin reduces atherosclerosis by inhibiting NF-κB and MAPK signaling pathways, reducing oxidative stress, modulating lipid metabolism, and increasing nitric oxide bioavailability. Curcumin has been shown in preclinical studies to reduce aortic lesion area, inhibit pro-inflammatory cytokines, and improve endothelial function, and clinical trials show that it has the potential to improve vascular health in at-risk groups. However, issues such as low bioavailability demand additional research into improved formulations. By integrating current information, this article highlights curcumin's therapeutic potential and advocates for robust clinical trials to validate its efficacy and establish standardized dose regimens for cardiovascular disease prevention and treatment.
Nucleolin (NCL) is a multifunctional, highly conserved protein that shuttles between the nucleus, cytoplasm, and cell surface, playing pivotal roles in cellular homeostasis and disease. In recent years, NCL has emerged as a central host factor exploited by a wide array of viruses-including Herpesviridae, Flaviviridae, Pneumoviridae, Picornaviridae, Orthomyxoviridae, Coronaviridae, Caliciviridae, and Morbillivirus-to facilitate viral entry, replication, assembly, and immune evasion. This review provides a comprehensive, comparative synthesis of the mechanisms by which diverse viruses hijack distinct structural domains of nucleolin, highlighting both proviral and antiviral activities that are context- and compartment-dependent. We critically evaluated the strength and limitations of current evidence, discuss contradictory findings across virus families, and identify patterns in domain-specific and compartmentalized viral exploitation of NCL. Special emphasis is placed on recent advances in targeting nucleolin-virus interactions for therapeutic intervention, including aptamers, G-quadruplex stabilizers, and domain-specific inhibitors. While nucleolin's essential cellular functions present challenges for drug development, emerging strategies that exploit its unique roles in viral pathogenesis offer promising avenues for broad-spectrum and precision antivirals. By integrating mechanistic insights across virus families, this review positions nucleolin as a universal node in viral infection and a compelling target for next-generation antiviral therapies.
Helicobacter pylori is a pathogenic bacterium that causes various gastric diseases in humans. It secretes virulence factors such as the CagA protein, which plays a crucial role in its pathogenesis. The C-terminal domain (CTD) of the CagA protein plays a crucial role in facilitating its attachment to host cell membranes and interacting with various intracellular proteins. These interactions are essential for the growth and infection of H. pylori. Strain-specific sequence polymorphism of H. pylori, specifically at the C-terminal of the CagA protein, is responsible for its differential oncogenic potential. Curcumin is a natural compound with pharmacological properties like anti-oxidant, anti-bacterial, anti-inflammatory, and anti-cancer effects. Additionally, several studies have reported the anti-H. pylori effects of curcumin. In this study, we investigated mechanisms of binding of curcumin and its non-oxidizable derivatives (acetalcurcumin and diacetalcurcumin) with CTD of CagA protein. We used computational strategies such as docking and molecular dynamics simulation for the analysis. Curcumin was found to have more binding affinity with the CagA protein than its acetal and diacetal analogs. This suggests that the OH-group present in the structure of curcumin, which gets modified in its acetal and diacetal analogs, may have an essential role in the interaction with the CagA protein. Results showed that curcumin binds to the residues within the active pocket formed by the EPIYA-C motif and CM motif located in the C-terminal domain (CTD) of the CagA protein. Additionally, curcumin was observed to interact with the TYR970 residue within the EPIYA-C motif of the CTD of the CagA protein. Notably, TYR970 phosphorylation is a known event during H. pylori-mediated pathogenesis. Therefore, this study suggests that curcumin's anti-H. pylori activity may be triggered by inhibiting the phosphorylation of the CagA protein.
This review traces the development of vaccines from ancient times to the present, highlighting major milestones and challenges. It covers the significant impact of vaccines on public health, including the eradication of diseases such as smallpox and the reduction of others such as polio, measles, and influenza. The review provides an in-depth look at the COVID-19 vaccines, which were developed at unprecedented speeds due to the urgent global need. The study emphasizes the ongoing potential of vaccine development to address future global health challenges, demonstrating the critical role vaccines play in disease prevention and public health. Moreover, it discusses the evolution of vaccine technology, from live-attenuated and inactivated vaccines to modern recombinant and mRNA vaccines, showcasing the advancements that have enabled rapid responses to emerging infectious diseases. The review underscores the importance of continued investment in research and development, global collaboration, and the adoption of new technologies to enhance vaccine efficacy and coverage. By exploring historical and contemporary examples, the article illustrates how vaccines have transformed medical practice and public health outcomes, providing valuable insights into future directions for vaccine innovation and deployment.
Targeting interactions between a virus and a host protein is one of the important approaches to developing antiviral therapies. We previously identified host nucleolin as a novel interacting partner of the influenza A virus nucleoprotein, and it was demonstrated that this interaction restricts virus replication. In the current study, we examined the interaction of nucleolin with the viral nucleoprotein at the domain and amino acid levels using in vitro and in silico approaches. Both approaches demonstrated a direct and specific interaction between these two proteins. Furthermore, it was observed that previous pandemic strains of influenza A virus had specific amino acid residues in their nucleoproteins that were predicted to be critical for interaction with nucleolin. This preliminary analysis provides insights into the binding process, which could be explored for developing antiviral strategies.
Since the dawn of time, several uses for vegetable oils have been known to exist such as in the nutritional, industrial, biofuel and pharmaceutical industries. Vegetable oils have significant pharmacological properties as antioxidant, anti-inflammatory, antifungal, antipyretic, analgesic, antibacterial, and anti-hyperglycemia that have gained popularity in the pharmaceutical industry. These oils are incredibly popular for treatment of many illnesses among the general public in nations like India due to their significant efficacy, manageable cost, low adverse effect profile, and favourable efficacy. Vegetable oils like Sunflower, sweet almond, olive and coconut oils, etc., were successfully used in the improvement of liver functioning, boosting immunity, encouraging hair development, and treating skin and scalp conditions, superficial wounds, sore throats, obesity, cancer and many other pathological conditions. Numerous different oils have been employed, and newer ones are always being developed. Vegetable oils have been incorporated into nanoemulsions which is thought to be a viable method for making these natural substances more usable and for amplifying their effects. A promising area for the treatment of several illnesses is the creation of lipid nanoparticles using vegetable oils. The purpose of this review is to report on some properties and uses and assess current studies that have been published in the literature about the use of vegetable oils with therapeutic properties.
Curcumin is a hydrophobic polyphenol derived from turmeric with potent anti-oxidant, anti-microbial, anti-inflammatory and anti-carcinogenic effects. Curcumin is degraded into various derivatives under in vitro and in vivo conditions, and it appears that its degradation may be responsible for the pharmacological effects of curcumin. The primary risk factor for the cause of gastric cancer is Helicobacter pylori (H. pylori). A virulence factor vacuolating cytotoxic A (VacA) is secreted by H. pylori as a 88 kDa monomer (p88), which can be fragmented into a 33 kDa N-terminal domain (p33) and a 55 kDa C-terminal domain (p55). Recently it has been reported that curcumin oxidation is required to inhibit the activity of another major H.pylori toxin CagA. We performed molecular docking of curcumin and its oxidative derivatives with p33 and p55 domains of VacA. Further, we have examined the effect of the oxidation of curcumin on the vacuolation activity of VacA protein. We observed the binding of curcumin to the p55 domain of VacA at five different sites with moderate binding affinities. Curcumin did not bind to p33 domain of VacA. Remarkably, cyclobutyl cyclopentadione and dihydroxy cyclopentadione, which are oxidized products of curcumin, showed a higher binding affinity with VacA protein at all sites except one as compared to parent curcumin itself. However, cyclobutyl cyclopentadione showed a significant binding affinity for the active site 5 of the p55 protein. Active site five (312–422) of p55 domain of VacA plays a crucial role in VacA-mediated vacuole formation. Invitro experiments showed that curcumin inhibited the vacuolation activity of H. pylori in human gastric cell line AGS cells whereas acetyl and diacetyl curcumin, which cannot be oxidized, failed to inhibit the vacuolation in AGS cells after H. pylori infection. Here our data showed that oxidation is essential for the activity of curcumin in inhibiting the vacuolation activity of H. pylori. Synthesis of these oxidized curcumin derivatives could potentially provide new therapeutic drug molecules for inhibiting H. pylori-mediated pathogenesis.
Curcumin is a potential natural remedy for preventing Helicobacter pylori-associated gastric inflammation and cancer. Here, we analyzed the effect of a phospholipid formulation of curcumin on H. pylori growth, translocation and phosphorylation of the virulence factor CagA and host protein kinase Src in vitro and in an in vivo mouse model of H. pylori infection. Growth of H. pylori was inhibited dose-dependently by curcumin in vitro. H. pylori was unable to metabolically reduce curcumin, whereas two enterobacteria, E. coli and Citrobacter rodentium, which efficiently reduced curcumin to the tetra- and hexahydro metabolites, evaded growth inhibition. Oxidative metabolism of curcumin was required for the growth inhibition of H. pylori and the translocation and phosphorylation of CagA and cSrc, since acetal- and diacetal-curcumin that do not undergo oxidative transformation were ineffective. Curcumin attenuated mRNA expression of the H. pylori virulence genes cagE and cagF in a dose-dependent manner and inhibited translocation and phosphorylation of CagA in gastric epithelial cells. H. pylori strains isolated from dietary curcumin-treated mice showed attenuated ability to induce cSrc phosphorylation and the mRNA expression of the gene encoding for IL-8, suggesting long-lasting effects of curcumin on the virulence of H. pylori. Our work provides mechanistic evidence that encourages testing of curcumin as a dietary approach to inhibit the virulence of CagA.
Curcumin, a secondary metabolite from the turmeric plant is one of the most promising natural products, which has been studied extensively for decades. It has demonstrated several pharmacological activities in vitro and in vivo. Various studies have indicated that the pharmacological activity of curcumin is contributed by its metabolites. The aim of this review is to present an overview of metabolic products of curcumin produced upon its reduction like di, tetra, hexa and octa-hydrocurcumin. In addition, this paper has systematically analyzed the current information regarding medicinal use of reduced metabolites of curcumin and identified the limitations which have hindered its widespread usage in the medical world. Several diverse therapeutic effects have shown to be exhibited by reduced metabolites of curcumin such as antioxidant, anti-cancerous, anti-inflammatory and immunoregulatory activities. The potential underlying molecular mechanisms of the biological activities of reduced metabolites of curcumin have also been highlighted, which may provide insight into the principle of effectiveness of curcumin.
Viral infections are responsible for many illnesses, and recent outbreaks have raised public health concerns. Despite the availability of many antiviral drugs, they are often unsuccessful due to the generation of viral mutants and less effective against their target virus. Identifying novel antiviral drugs is therefore of critical importance and natural products are an excellent source for such discoveries. Coumarin is one such natural compound that is a potential drug candidate owing to its properties of stability, solubility, and low toxicity. There are numerous evidences showing its inhibitory role against infection of various viruses such as HIV, Influenza, Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16). The mechanisms involve either inhibition of proteins essential for viral entry, replication and infection or regulation of cellular pathways such as Akt-Mtor (mammalian target of rapamycin), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), and anti-oxidative pathway including NrF-2 (The nuclear factor erythroid 2 (NFE2)-related factor 2). This review summarizes the present state of understanding with a focus on coumarin's antiviral effect and their possible molecular mechanisms against Influenza virus, HIV, Hepatitis virus, Dengue virus and Chikungunya virus.