Regulation of Zbp1 by miR-99b-5p in microglia controls the development of schizophrenia-like symptoms in mice.

Current approaches to the treatment of schizophrenia have mainly focused on the protein-coding part of the genome; in this context, the roles of microRNAs have received less attention. In the present study, we analyze the microRNAome in the blood and postmortem brains of schizophrenia patients, showing that the expression of miR-99b-5p is downregulated in both the prefrontal cortex and blood of patients. Lowering the amount of miR-99b-5p in mice leads to both schizophrenia-like phenotypes and inflammatory processes that are linked to synaptic pruning in microglia. The microglial miR-99b-5p-supressed inflammatory response requires Z-DNA binding protein 1 (Zbp1), which we identify as a novel miR-99b-5p target. Antisense oligonucleotides against Zbp1 ameliorate the pathological effects of miR-99b-5p inhibition. Our findings indicate that a novel miR-99b-5p-Zbp1 pathway in microglia might contribute to the pathogenesis of schizophrenia.

Gamma entrainment using audiovisual stimuli alleviates chemobrain pathology and cognitive impairment induced by chemotherapy in mice.

Patients with cancer undergoing chemotherapy frequently experience a neurological condition known as chemotherapy-related cognitive impairment, or "chemobrain," which can persist for the remainder of their lives. Despite the growing prevalence of chemobrain, both its underlying mechanisms and treatment strategies remain poorly understood. Recent findings suggest that chemobrain shares several characteristics with neurodegenerative diseases, including chronic neuroinflammation, DNA damage, and synaptic loss. We investigated whether a noninvasive sensory stimulation treatment we term gamma entrainment using sensory stimuli (GENUS), which has been shown to alleviate aberrant immune and synaptic pathologies in mouse models of neurodegeneration, could also mitigate chemobrain phenotypes in mice administered a chemotherapeutic drug. When administered concurrently with the chemotherapeutic agent cisplatin, GENUS alleviated cisplatin-induced brain pathology, promoted oligodendrocyte survival, and improved cognitive function in a mouse model of chemobrain. These effects persisted for up to 105 days after GENUS treatment, suggesting the potential for long-lasting benefits. However, when administered to mice 90 days after chemotherapy, GENUS treatment only provided limited benefits, indicating that it was most effective when used to prevent the progression of chemobrain pathology. Furthermore, we demonstrated that the effects of GENUS in mice were not limited to cisplatin-induced chemobrain but also extended to methotrexate-induced chemobrain. Collectively, these findings suggest that GENUS may represent a versatile approach for treating chemobrain induced by different chemotherapy agents.

Multisensory gamma stimulation promotes glymphatic clearance of amyloid.

The glymphatic movement of fluid through the brain removes metabolic waste1-4. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer's disease5-8. Here we show that multisensory gamma stimulation promotes the influx of cerebrospinal fluid and the efflux of interstitial fluid in the cortex of the 5XFAD mouse model of Alzheimer's disease. Influx of cerebrospinal fluid was associated with increased aquaporin-4 polarization along astrocytic endfeet and dilated meningeal lymphatic vessels. Inhibiting glymphatic clearance abolished the removal of amyloid by multisensory 40 Hz stimulation. Using chemogenetic manipulation and a genetically encoded sensor for neuropeptide signalling, we found that vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility. Our findings establish novel mechanisms that recruit the glymphatic system to remove brain amyloid.

A Single-Cell Transcriptomic Analysis of the Mouse Hippocampus After Voluntary Exercise.

Exercise has been recognized as a beneficial factor for cognitive health, particularly in relation to the hippocampus, a vital brain region responsible for learning and memory. Previous research has demonstrated that exercise-mediated improvement of learning and memory in humans and rodents correlates with increased adult neurogenesis and processes related to enhanced synaptic plasticity. Nevertheless, the underlying molecular mechanisms are not fully understood. With the aim to further elucidate these mechanisms, we provide a comprehensive dataset of the mouse hippocampal transcriptome at the single-cell level after 4 weeks of voluntary wheel-running. Our analysis provides a number of interesting observations. For example, the results suggest that exercise affects adult neurogenesis by accelerating the maturation of a subpopulation of Prdm16-expressing neurons. Moreover, we uncover the existence of an intricate crosstalk among multiple vital signaling pathways such as NF-κB, Wnt/ß-catenin, Notch, and retinoic acid (RA) pathways altered upon exercise in a specific cluster of excitatory neurons within the Cornu Ammonis (CA) region of the hippocampus. In conclusion, our study provides an important resource dataset and sheds further light on the molecular changes induced by exercise in the hippocampus. These findings have implications for developing targeted interventions aimed at optimizing cognitive health and preventing age-related cognitive decline.

A clinical study and future prospects for bioactive compounds and semi-synthetic molecules in the therapies for Huntington's disease.

A neurodegenerative disorder (ND) refers to Huntington's disease (HD) which affects memory loss, weight loss, and movement dysfunctions such as chorea and dystonia. In the striatum and brain, HD most typically impacts medium-spiny neurons. Molecular genetics, excitotoxicity, oxidative stress (OS), mitochondrial, and metabolic dysfunction are a few of the theories advanced to explicit the pathophysiology of neuronal damage and cell death. Numerous in-depth studies of the literature have supported the therapeutic advantages of natural products in HD experimental models and other treatment approaches. This article briefly discusses the neuroprotective impacts of natural compounds against HD models. The ability of the discovered natural compounds to suppress HD was tested using either in vitro or in vivo models. Many bioactive compounds considerably lessened the memory loss and motor coordination brought on by 3-nitropropionic acid (3-NP). Reduced lipid peroxidation, increased endogenous enzymatic antioxidants, reduced acetylcholinesterase activity, and enhanced mitochondrial energy generation have profoundly decreased the biochemical change. It is significant since histology showed that therapy with particular natural compounds lessened damage to the striatum caused by 3-NP. Moreover, natural products displayed varying degrees of neuroprotection in preclinical HD studies because of their antioxidant and anti-inflammatory properties, maintenance of mitochondrial function, activation of autophagy, and inhibition of apoptosis. This study highlighted about the importance of bioactive compounds and their semi-synthetic molecules in the treatment and prevention of HD.

Targeted therapies of curcumin focus on its therapeutic benefits in cancers and human health: Molecular signaling pathway-based approaches and future perspectives.

The curry powder spices turmeric (Curcuma longa L.), which contains curcumin (diferuloylmethane), an orange-yellow chemical. Polyphenols are the most commonly used sources of curcumin. It combats oxidative stress and inflammation in diseases, such as hyperlipidemia, metabolic syndrome, arthritis, and depression. Most of these benefits are due to their anti-inflammatory and antioxidant properties. Curcumin consumption leads to decreased bioavailability, resulting in limited absorption, quick metabolism, and quick excretion, which hinders health improvement. Numerous factors can increase its bioavailability. Piperine enhances bioavailability when combined with curcumin in a complex. When combined with other enhancing agents, curcumin has a wide spectrum of health benefits. This review evaluates the therapeutic potential of curcumin with a specific emphasis on its approach based on molecular signaling pathways. This study investigated its influence on the progression of cancer, inflammation, and many health-related mechanisms, such as cell proliferation, apoptosis, and metastasis. Curcumin has a significant potential for the prevention and treatment of various diseases. Curcumin modulates several biochemical pathways and targets involved in cancer growth. Despite its limited tissue accumulation and bioavailability when administered orally, curcumin has proven useful. This review provides an in-depth analysis of curcumin's therapeutic applications, its molecular signaling pathway-based approach, and its potential for precision medicine in cancer and human health.

Novel computational and drug design strategies for the inhibition of human T-cell leukemia virus 1-associated lymphoma by Astilbin derivatives.

Human T-cell leukemia virus 1 (HTLV-1) associated lymphoma is a devastating malignancy triggered by HTLV-1 infections. We employeda comprehensive drug design and computational strategy in this work to explore the inhibitory activitiesof Astilbin derivatives against HTLV-1-associated lymphoma. We evaluated the stability, binding affinities, and various computational analysis of Astilbin derivatives against target proteins, such as HTLV-1 main protease and HTLV-1 capsid protein. The root mean square deviation (RMSD), root mean square fluctuation, radius of gyration, hydrogen bond analysis, principal component analysis (PCA) and dynamic cross-correlation matrix (DCCM) were applied to characterize these protein-ligand interactions further. Ligand-03 and ligand-04 exhibited notable binding affinity to HTLV-1 capsid protein, while ligand-05 displayed high binding affinity to HTLV-1 protease. MD simulation analysis revealed that ligand-03, bound to HTLV-1 capsid protein, demonstrated enhanced stability with lower RMSD values and fewer conformational changes, suggesting a promising binding orientation. Ligand-04, despite stable binding, exhibited increased structural deviations, making it less suitable. Ligand-05 demonstrated stable binding to HTLV-1 protease throughout the simulation period at 100 nanoseconds. Hydrogen bond analysis indicated that ligand-05 formed persistent hydrogen bonds with significantresidues, contributing to its stability. PCA highlighted ligand-03's more remarkable conformational changes, while DCCM showed ligand-05's distinct dynamics, indicating its different behavior in the complex. Furthermore, binding free energy calculations supported the favorable interactions of ligand-03 and ligand-04 with HTLV-1 capsid protein, while ligand-05 showed weaker interactions with HTLV-1 protease. Molecular electrostatic potential and frontier molecular orbital analyses provided insights into these compounds' charge distribution and stability. In conclusion, this research found Astilbin derivatives as potential inhibitors of HTLV-1-associated lymphoma. Future attempts at drug development will benefit from the steady interaction landscape provided by Ligand-03, Ligand-04 and Ligand-05, which showed the most attractive binding profile with the target protein. These results open up new opportunities for innovative drug development, and more experimental testing should be done between Astilbin derivatives and HTLV-1-associated lymphoma.Communicated by Ramaswamy H. Sarma.

Bioactive molecules from terrestrial and seafood resources in hypertension treatment: focus on molecular mechanisms and targeted therapies.

Hypertension (HTN), a complex cardiovascular disease (CVD), significantly impacts global health, prompting a growing interest in complementary and alternative therapeutic approaches. This review article seeks to provide an up-to-date and thorough summary of modern therapeutic techniques for treating HTN, with an emphasis on the molecular mechanisms of action found in substances found in plants, herbs, and seafood. Bioactive molecules have been a significant source of novel therapeutics and are crucial in developing and testing new HTN remedies. Recent advances in science have made it possible to understand the complex molecular mechanisms underlying blood pressure (BP)-regulating effects of these natural substances better. Polyphenols, flavonoids, alkaloids, and peptides are examples of bioactive compounds that have demonstrated promise in influencing several pathways involved in regulating vascular tone, reducing oxidative stress (OS), reducing inflammation, and improving endothelial function. The article explains the vasodilatory, diuretic, and renin-angiotensin-aldosterone system (RAAS) modifying properties of vital plants such as garlic and olive leaf. Phytochemicals from plants are the primary in traditional drug development as models for novel antihypertensive drugs, providing diverse strategies to combat HTN due to their biological actions. The review also discusses the functions of calcium channel blockers originating from natural sources, angiotensin-converting enzyme (ACE) inhibitors, and nitric oxide (NO) donors. Including seafood components in this study demonstrates the increased interest in using bioactive chemicals originating from marine sources to treat HTN. Omega-3 fatty acids, peptides, and minerals obtained from seafood sources have anti-inflammatory, vasodilatory, and antioxidant properties that improve vascular health and control BP. Overall, we discussed the multiple functions of bioactive molecules and seafood components in the treatment of HTN.

Novel computational and drug design strategies for inhibition of human papillomavirus-associated cervical cancer and DNA polymerase theta receptor by Apigenin derivatives.

The present study deals with the advanced in-silico analyses of several Apigenin derivatives to explore human papillomavirus-associated cervical cancer and DNA polymerase theta inhibitor properties by molecular docking, molecular dynamics, QSAR, drug-likeness, PCA, a dynamic cross-correlation matrix and quantum calculation properties. The initial literature study revealed the potent antimicrobial and anticancer properties of Apigenin, prompting the selection of its potential derivatives to investigate their abilities as inhibitors of human papillomavirus-associated cervical cancer and DNA polymerase theta. In silico molecular docking was employed to streamline the findings, revealing promising energy-binding interactions between all Apigenin derivatives and the targeted proteins. Notably, Apigenin 4'-O-Rhamnoside and Apigenin-4'-Alpha-L-Rhamnoside demonstrated higher potency against the HPV45 oncoprotein E7 (PDB ID 2EWL), while Apigenin and Apigenin 5-O-Beta-D-Glucopyranoside exhibited significant binding energy against the L1 protein in humans. Similarly, a binding affinity range of - 7.5 kcal/mol to - 8.8 kcal/mol was achieved against DNA polymerase theta, indicating the potential of Apigenin derivatives to inhibit this enzyme (PDB ID 8E23). This finding was further validated through molecular dynamic simulation for 100 ns, analyzing parameters such as RMSD, RMSF, SASA, H-bond, and RoG profiles. The results demonstrated the stability of the selected compounds during the simulation. After passing the stability testing, the compounds underwent screening for ADMET, pharmacokinetics, and drug-likeness properties, fulfilling all the necessary criteria. QSAR, PCA, dynamic cross-correlation matrix, and quantum calculations were conducted, yielding satisfactory outcomes. Since this study utilized in silico computational approaches and obtained outstanding results, further validation is crucial. Therefore, additional wet-lab experiments should be conducted under in vivo and in vitro conditions to confirm the findings.

A drug design strategy based on molecular docking and molecular dynamics simulations applied to development of inhibitor against triple-negative breast cancer by Scutellarein derivatives.

Triple-negative breast cancer (TNBC), accounting for 10-15% of all breast malignancies, is more prevalent in women under 40, particularly in those of African descent or carrying the BRCA1 mutation. TNBC is characterized by the absence of estrogen and progesterone receptors (ER, PR) and low or elevated HER2 expression. It represents a particularly aggressive form of breast cancer with limited therapeutic options and a poorer prognosis. In our study, we utilized the protein of TNBC collected from the Protein Data Bank (PDB) with the most stable configuration. We selected Scutellarein, a bioactive molecule renowned for its anti-cancer properties, and used its derivatives to design potential anti-cancer drugs employing computational tools. We applied and modified structural activity relationship methods to these derivatives and evaluated the probability of active (Pa) and inactive (Pi) outcomes using pass prediction scores. Furthermore, we employed in-silico approaches such as the assessment of absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and quantum calculations through density functional theory (DFT). Within the DFT calculations, we analyzed Frontier Molecular Orbitals, specifically the Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO). We then conducted molecular docking and dynamics against TNBC to ascertain binding affinity and stability. Our findings indicated that Scutellarein derivatives, specifically DM03 with a binding energy of -10.7 kcal/mol and DM04 with -11.0 kcal/mol, exhibited the maximum binding tendency against Human CK2 alpha kinase (PDB ID 7L1X). Molecular dynamic simulations were performed for 100 ns, and stability was assessed using root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) parameters, suggesting significant stability for our chosen compounds. Furthermore, these molecules met the pharmacokinetics requirements for potential therapeutic candidates, displaying non-carcinogenicity, minimal aquatic and non-aquatic toxicity, and greater aqueous solubility. Collectively, our computational data suggest that Scutellarein derivatives may serve as potential therapeutic agents for TNBC. However, further experimental investigations are needed to validate these findings.

Natural polymers as potential P-glycoprotein inhibitors: Pre-ADMET profile and computational analysis as a proof of concept to fight multidrug resistance in cancer.

P-glycoprotein (P-gp) is known as the "multidrug resistance protein" because it contributes to tumor resistance to several different classes of anticancer drugs. The effectiveness of such polymers in treating cancer and delivering drugs has been shown in a wide range of in vitro and in vivo experiments. The primary objective of the present study was to investigate the inhibitory effects of several naturally occurring polymers on P-gp efflux, as it is known that P-gp inhibition can impede the elimination of medications. The objective of our study is to identify polymers that possess the potential to inhibit P-gp, a protein involved in drug resistance, with the aim of enhancing the effectiveness of anticancer drug formulations. The ADMET profile of all the selected polymers (Agarose, Alginate, Carrageenan, Cyclodextrin, Dextran, Hyaluronic acid, and Polysialic acid) has been studied, and binding affinities were investigated through a computational approach using the recently released crystal structure of P-gp with PDB ID: 7O9W. The advanced computational study was also done with the help of molecular dynamics simulation. The aim of the present study is to overcome MDR resulting from the activity of P-gp by using such polymers that can inhibit P-gp when used in formulations. The docking scores of native ligand, Agarose, Alginate, Carrageenan, Chitosan, Cyclodextrin, Dextran, Hyaluronic acid, and Polysialic acid were found to be -10.7, -8.5, -6.6, -8.7, -8.6, -24.5, -6.7, -8.3, and -7.9, respectively. It was observed that, Cyclodextrin possess multiple properties in drug delivery science and here also demonstrated excellent binding affinity. We propose that drug efflux-related MDR may be prevented by the use of Agarose, Carregeenan, Chitosan, Cyclodextrin, Hyaluronic acid, and/or Polysialic acid in the administration of anticancer drugs.

Novel computational and drug design strategies for inhibition of monkeypox virus and Babesia microti: molecular docking, molecular dynamic simulation and drug design approach by natural compounds.

Background: The alarming increase in tick-borne pathogens such as human Babesia microti is an existential threat to global public health. It is a protozoan parasitic infection transmitted by numerous species of the genus Babesia. Second, monkeypox has recently emerged as a public health crisis, and the virus has spread around the world in the post-COVID-19 period with a very rapid transmission rate. These two novel pathogens are a new concern for human health globally and have become a significant obstacle to the development of modern medicine and the economy of the whole world. Currently, there are no approved drugs for the treatment of this disease. So, this research gap encourages us to find a potential inhibitor from a natural source. Methods and materials: In this study, a series of natural plant-based biomolecules were subjected to in-depth computational investigation to find the most potent inhibitors targeting major pathogenic proteins responsible for the diseases caused by these two pathogens. Results: Among them, most of the selected natural compounds are predicted to bind tightly to the targeted proteins that are crucial for the replication of these novel pathogens. Moreover, all the molecules have outstanding ADMET properties such as high aqueous solubility, a higher human gastrointestinal absorption rate, and a lack of any carcinogenic or hepatotoxic effects; most of them followed Lipinski's rule. Finally, the stability of the compounds was determined by molecular dynamics simulations (MDs) for 100 ns. During MDs, we observed that the mentioned compounds have exceptional stability against selected pathogens. Conclusion: These advanced computational strategies reported that 11 lead compounds, including dieckol and amentoflavone, exhibited high potency, excellent drug-like properties, and no toxicity. These compounds demonstrated strong binding affinities to the target enzymes, especially dieckol, which displayed superior stability during molecular dynamics simulations. The MM/PBSA method confirmed the favorable binding energies of amentoflavone and dieckol. However, further in vitro and in vivo studies are necessary to validate their efficacy. Our research highlights the role of Dieckol and Amentoflavone as promising candidates for inhibiting both monkeypox and Babesia microti, demonstrating their multifaceted roles in the control of these pathogens.

Target specific inhibition of West Nile virus envelope glycoprotein and methyltransferase using phytocompounds: an in silico strategy leveraging molecular docking and dynamics simulation.

Mosquitoes are the primary vector for West Nile virus, a flavivirus. The virus's ability to infiltrate and establish itself in increasing numbers of nations has made it a persistent threat to public health worldwide. Despite the widespread occurrence of this potentially fatal disease, no effective treatment options are currently on the market. As a result, there is an immediate need for the research and development of novel pharmaceuticals. To begin, molecular docking was performed on two possible West Nile virus target proteins using a panel of twelve natural chemicals, including Apigenin, Resveratrol, Hesperetin, Fungisterol, Lucidone, Ganoderic acid, Curcumin, Kaempferol, Cholic acid, Chlorogenic acid, Pinocembrin, and Sanguinarine. West Nile virus methyltransferase (PDB ID: 2OY0) binding affinities varied from -7.4 to -8.3 kcal/mol, whereas West Nile virus envelope glycoprotein affinities ranged from -6.2 to -8.1 kcal/mol (PDB ID: 2I69). Second, substances with larger molecular weights are less likely to be unhappy with the Lipinski rule. Hence, additional research was carried out without regard to molecular weight. In addition, compounds 01, 02, 03, 05, 06, 07, 08, 09, 10 and 11 are more soluble in water than compound 04 is. Besides, based on maximum binding affinity, best three compounds (Apigenin, Curcumin, and Ganoderic Acid) has been carried out molecular dynamic simulation (MDs) at 100 ns to determine their stability. The MDs data is also reported that these mentioned molecules are highly stable. Finally, advanced principal component analysis (PCA), dynamics cross-correlation matrices (DCCM) analysis, binding free energy and dynamic cross correlation matrix (DCCM) theoretical study is also included to established mentioned phytochemical as a potential drug candidate. Research has indicated that the aforementioned natural substances may be an effective tool in the battle against the dangerous West Nile virus. This study aims to locate a bioactive natural component that might be used as a pharmaceutical.

Pomegranate-specific natural compounds as onco-preventive and onco-therapeutic compounds: Comparison with conventional drugs acting on the same molecular mechanisms.

Pomegranate, scientifically known as Punica granatum, has been a traditional medicinal remedy since ancient times. Research findings have shown that using pomegranate extracts can positively affect a variety of signaling pathways, including those involved in angiogenesis, inflammation, hyperproliferation, cellular transformation, the beginning stages of tumorigenesis, and lastly, a reduction in the final stages of metastasis and tumorigenesis. This is due to the fact that pomegranate extracts are rich in polyphenols, which are known to inhibit the activity of certain signaling pathways. In the United States, cancer is the second biggest cause of death after heart disease. The number of fatalities caused by cancer in the United States escalates yearly. Altering one's diet, getting involved in regular physical activity, and sustaining a healthy body weight are three easy steps an individual may follow to lower their cancer risk. Simply garnishing one's diet with vegetables and fruits has the potential to avert at least 20% of all cancer diagnoses and around 200,000 deaths caused by cancer each year. Vegetables, fruits, and other dietary constituents, such as minerals and phytochemicals, are currently being researched for their potential to prevent cancer. It is being done because they are safe, have minimal toxicity, possess antioxidant properties, and are universally accepted as dietary supplements. Ancient civilizations used the fruit of pomegranate (Punica granatum L.) to prevent and cure a number of diseases. The anti-tumorigenic, anti-inflammatory and anti-proliferative qualities of pomegranate have been shown in studies with the fruit, juice, extract, and oil of the pomegranate. Pomegranate has the capacity to affect several signaling pathways, which implies that it may have the potential to be employed not only as a chemopreventive agent but also as a chemotherapeutic drug. This article elaborates on some recent preclinical and clinical research which shows that pomegranate seems to have a role in the prevention and treatment of a number of cancers, including but not limited to breast, bladder, skin, prostate, colon, and lung cancer, among others.

Development of a new drug candidate for the inhibition of Lassa virus glycoprotein and nucleoprotein by modification of evodiamine as promising therapeutic agents.

The Lassa virus (LASV), an RNA virus prevalent in West and Central Africa, causes severe hemorrhagic fever with a high fatality rate. However, no FDA-approved treatments or vaccines exist. Two crucial proteins, LASV glycoprotein and nucleoprotein, play vital roles in pathogenesis and are potential therapeutic targets. As effective treatments for many emerging infections remain elusive, cutting-edge drug development approaches are essential, such as identifying molecular targets, screening lead molecules, and repurposing existing drugs. Bioinformatics and computational biology expedite drug discovery pipelines, using data science to identify targets, predict structures, and model interactions. These techniques also facilitate screening leads with optimal drug-like properties, reducing time, cost, and complexities associated with traditional drug development. Researchers have employed advanced computational drug design methods such as molecular docking, pharmacokinetics, drug-likeness, and molecular dynamics simulation to investigate evodiamine derivatives as potential LASV inhibitors. The results revealed remarkable binding affinities, with many outperforming standard compounds. Additionally, molecular active simulation data suggest stability when bound to target receptors. These promising findings indicate that evodiamine derivatives may offer superior pharmacokinetics and drug-likeness properties, serving as a valuable resource for professionals developing synthetic drugs to combat the Lassa virus.

Oleuropein: Chemistry, extraction techniques and nutraceutical perspectives-An update.

Olive family (Oleaceae) contains several species among which Olea europaea L. is mostly used for production of olive oils. Various parts of olive tree are rich source of diverse bioactive compounds such as Apigenin, elenolic acid, Hydroxytyrosol, Ligstroside, Oleoside, Oleuropein, Oleuropein aglycone, Tyrosol, etc. Among these, oleuropein, a secoiridoid is predominantly found in olive leaves and young olive fruits of different species of Oleaceae family. Scientists have adopted numerous extraction methods (conventional & latest) to increase the yield of oleuropein. Among these techniques, maceration, soxhlet, microwave-assisted, ultrasonication, and supercritical fluid methods are most commonly employed for extraction of oleuropein. Evidently, this review emphasizes on various in-vitro and in-vivo studies focusing on nutraceutical properties of oleuropein. Available literature highlights the pharmaceutical potential of oleuropein against various diseases such as obesity, diabetes, cardiovascular complications, neurodegenerative diseases, cancer, inflammation, microbial infections, and oxidation. This review will benefit the scientific community as it narrates comprehensive literature regarding absorption, metabolism, bioavailability, extraction techniques, and nutraceutical perspectives associated with oleuropein.