Cholesterol Absorption Inhibition by Some Nutraceuticals.

Hyperlipidemia, characterized by elevated levels of lipids in the blood, represents a major risk factor for cardiovascular diseases, a leading cause of morbidity and mortality worldwide. Conventional pharmacological interventions have been effective in managing hyperlipidemia, but concerns about side effects and long-term use have prompted interest in alternative approaches, particularly the use of nutraceuticals. This comprehensive review aims to summarize and critically evaluate the current body of knowledge surrounding the role of nutraceuticals in the management of hyperlipidemia. We provide an overview of the different classes of nutraceuticals, including plant sterols, omega-3 fatty acids, soluble fiber, antioxidants, and various herbal extracts, which have been investigated for their lipid-lowering properties. The mechanisms of action of these nutraceuticals are discussed, highlighting their ability to modulate lipid metabolism, reduce oxidative stress, and promote cardiovascular health. Furthermore, we review the results of clinical trials and epidemiological studies that have assessed the efficacy of nutraceutical interventions in lowering cholesterol levels, improving lipid profiles, and reducing the risk of cardiovascular events. In addition to their lipid-lowering effects, we examine the safety profile, dosage recommendations, and potential interactions of nutraceuticals with conventional lipid-lowering medications. We also address the importance of patient adherence to dietary and lifestyle modifications in conjunction with nutraceutical supplementation. While nutraceuticals offer a promising avenue for managing hyperlipidemia, we emphasize the need for further research to establish evidence-based guidelines for their use in clinical practice. Challenges related to standardization, quality control, and regulatory considerations are also discussed. In conclusion, this comprehensive review provides valuable insights into the potential of nutraceuticals as adjunctive or alternative therapies for managing hyperlipidemia. While further research is needed, the accumulating evidence suggests that nutraceuticals can play a valuable role in promoting cardiovascular health and reducing the burden of hyperlipidemia- related diseases.

Recent Advances in Pharmaceutical Design: Unleashing the Potential of Novel Therapeutics.

Pharmaceutical design has made significant advancements in recent years, leading to the development of novel therapeutics with unprecedented efficacy and safety profiles. This review highlights the potential of these innovations to revolutionize healthcare and improve patient outcomes. The application of cutting-edge technologies like artificial intelligence, machine learning, and data mining in drug discovery and design has made it easier to find potential drug candidates. Combining big data and omics has led to the discovery of new therapeutic targets and personalized medicine strategies. Nanoparticles, liposomes, and microneedles are examples of advanced drug delivery systems that allow precise control over drug release, better bioavailability, and targeted delivery to specific tissues or cells. This improves the effectiveness of the treatment while reducing side effects. Stimuli-responsive materials and smart drug delivery systems enable drugs to be released on demand when specific internal or external signals are sent. Biologics and gene therapies are promising approaches in pharmaceutical design, offering high specificity and potency for treating various diseases like cancer, autoimmune disorders, and infectious diseases. Gene therapies hold tremendous potential for correcting genetic abnormalities, with recent breakthroughs demonstrating successful outcomes in inherited disorders and certain types of cancer. Advancements in nanotechnology and nanomedicine have paved the way for innovative diagnostic tools and therapeutics, such as nanoparticle-based imaging agents, targeted drug delivery systems, gene editing technologies, and regenerative medicine strategies. Finally, the review emphasizes the importance of regulatory considerations, ethical challenges, and future directions in pharmaceutical design. Regulatory agencies are adapting to the rapid advancements in the field, ensuring the safety and efficacy of novel therapeutics while fostering innovation. Ethical considerations regarding the use of emerging technologies, patient privacy, and access to advanced therapies also require careful attention.

Unveiling the Anti-Convulsant Potential of Novel Series of 1,2,4-Triazine-6H-Indolo[2,3-b]quinoline Derivatives: In Silico Molecular Docking, ADMET, DFT, and Molecular Dynamics Exploration.

BACKGROUND: Epilepsy is a chronic neurological disorder caused by irregular electrical activity in the brain. To manage this disorder effectively, it is imperative to identify potential pharmacological targets and to understand the pathophysiology of epilepsy in depth. OBJECTIVE: This research aimed to identify promising leads from a library of 1,2,4-triazine-6H-indolo[2,3-b]quinoline derivatives and optimize them using in silico and dynamic processes. METHODS: We used computational studies to examine 1,2,4-Triazine-6H-indolo[2,3-b]quinoline derivatives. Some methods were used to strengthen the stability of binding sites, including Docking, ADMET, IFD, MMGBSA, Density Functional Theory (DFT), and Molecular Dynamics. RESULTS: HRSN24 and HRSN34 exhibited promising pharmacokinetic and pharmacodynamic characteristics compared to standard drugs (Carbamazepine and Phenytoin) and a co-crystal ligand (Diazepam). Both HRSN24 and HRSN34 presented notable Glide Xp docking scores (-4.528 and -4.633 Kcal/mol), IFD scores (-702.22 and -700.3 Kcal/mol), and MMGBSA scores (-45.71 and -14.46 Kcal/mol). HRSN24 was selected for molecular dynamics and DFT analysis. During MD, HRSN24 identified LYS21, GLY22, ASP24, ARG26, VAL53, MET55, and SER308 as the most important amino acid residues for hydrophobic interactions. A DFT computation was performed to determine the physicochemical properties of HRSN24, revealing a total energy of -1362.28 atomic units, a HOMO value of -0.20186, and a LUMO value of -0.01915. CONCLUSION: Based on computational modelling techniques, an array of 1,2,4-Triazine-6H-indolo[2,3-b]quinoline derivatives were evaluated for their anti-convulsant properties. A stable compound within the GABAA receptor was identified by HRSN24, suggesting its affinity as an anti-convulsant.

A Comprehensive Review on Niosomes as a Tool for Advanced Drug Delivery.

Over the past few decades, advancements in nanocarrier-based therapeutic delivery have been significant, and niosomes research has recently received much interest. The self-assembled nonionic surfactant vesicles lead to the production of niosomes. The most recent nanocarriers, niosomes, are self-assembled vesicles made of nonionic surfactants with or without the proper quantities of cholesterol or other amphiphilic molecules. Because of their durability, low cost of components, large-scale production, simple maintenance, and high entrapment efficiency, niosomes are being used more frequently. Additionally, they enhance pharmacokinetics, reduce toxicity, enhance the solubility of poorly water-soluble compounds, & increase bioavailability. One of the most crucial features of niosomes is their controlled release and targeted diffusion, which is utilized for treating cancer, infectious diseases, and other problems. In this review article, we have covered all the fundamental information about niosomes, including preparation techniques, niosomes types, factors influencing their formation, niosomes evaluation, applications, and administration routes, along with recent developments.

Attenuation of Strychnine-Induced Epilepsy Employing Amaranthus viridis L. Leaves Extract in Experimental Rats.

Objective: Epilepsy is one of the most prevalent neurological illnesses defined by periodic seizures with or without loss of consciousness caused by aberrant neural activity. There are many allopathic medications available for the treatment of epilepsy such as phenytoin (PHY), but the side effects are a major concern. Therefore, the present study involved the evaluation of the pharmacological significance of Amaranthus viridis L. extract (EAV) in the management of strychnine (STR)-induced epilepsy. Method: STR (3.5 mg/kg, i.p.) was injected into male rats 30 minutes after the pre-treatment of a standard drug (PHY: 20 mg/kg) and the two doses of EAV (EAV-200 and EAV-400 mg/kg, p.o.) to the respective groups to cause the convulsions. The anti-convulsant effect of EAV-200 and EAV-400 against STR-induced convulsion in rats was investigated in terms of convulsion onset, duration of convulsions, number of convulsions, and convulsion score. Furthermore, the mitochondrial function and integrity in the brain's prefrontal cortex (PFC) were also estimated. Results: EAV-400 significantly increased the onset of convulsion from 61.67 ± 3.051 to 119.2 ± 2.738 and reduced the STR-induced duration of convulsions from 144.8 ± 3.582 to 69.17 ± 3.736, number of convulsions from 4.000 ± 0.1592 to 1.533 ± 0.1542, and convulsion score from 5.000 ± 0.3651 to 2.833 ± 0.3073 in rats. EAV-400 significantly attenuated the STR-induced decrease in the mitochondrial function and integrity of the rat PFC. In rats, EAV-400 significantly accelerated the onset of convulsions while decreasing the STR-induced duration, frequency, and score. Conclusion: Based on investigational findings, EAV-400 could be inferred to be a possible anti-epileptic option for the treatment of epilepsy of this plan in preclinical research.

Artificial Intelligence-Based Data-Driven Strategy to Accelerate Research, Development, and Clinical Trials of COVID Vaccine.

The global COVID-19 (coronavirus disease 2019) pandemic, which was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a significant loss of human life around the world. The SARS-CoV-2 has caused significant problems to medical systems and healthcare facilities due to its unexpected global expansion. Despite all of the efforts, developing effective treatments, diagnostic techniques, and vaccinations for this unique virus is a top priority and takes a long time. However, the foremost step in vaccine development is to identify possible antigens for a vaccine. The traditional method was time taking, but after the breakthrough technology of reverse vaccinology (RV) was introduced in 2000, it drastically lowers the time needed to detect antigens ranging from 5-15 years to 1-2 years. The different RV tools work based on machine learning (ML) and artificial intelligence (AI). Models based on AI and ML have shown promising solutions in accelerating the discovery and optimization of new antivirals or effective vaccine candidates. In the present scenario, AI has been extensively used for drug and vaccine research against SARS-COV-2 therapy discovery. This is more useful for the identification of potential existing drugs with inhibitory human coronavirus by using different datasets. The AI tools and computational approaches have led to speedy research and the development of a vaccine to fight against the coronavirus. Therefore, this paper suggests the role of artificial intelligence in the field of clinical trials of vaccines and clinical practices using different tools.

Antidepressive-Like Effect of Aegle marmelos Leaf Extract in Chronic Unpredictable Mild Stress-Induced Depression-Like Behaviour in Rats.

Background: Depression is a psychiatric disorder leading to anhedonia and lack of interest and motivation. Depressive symptoms are triggered by stressful life events, and patients with major depression are at significantly increased risk of attempting suicide. The crucial concern in depression treatment with antidepressant medications is that few weeks are required to show the therapeutic effect along with moderate side effects. The use of herbal medications is a new strategy for the treatment of depression which is often based on medicinal plants.Aegle marmelos (L.) Corr. (family: Rutaceae) is reported to have several actions on the central nervous system producing beneficial effects in anxiety, Alzheimer's disease, Parkinson's disease, epilepsy, and convulsion. Thus, the current investigation designed to assess the antidepressant activity of the standardized hydroethanolic extract of Aegle marmelos (EAM) leaves in male rats exposed to the chronic unpredictable mild stress (CUMS) paradigm. Methods: Rats were divided in 5 groups. The control group was not subjected to experimental CUMS paradigm, while 4 other groups were subjected to CUMS paradigm to induce depression-like behaviour from day 1 to day 28. Following the CUMS paradigm, 4 groups were divided as CUMS disease control, CUMS+EAM (150 mg/kg, p.o.), CUMS+EAM (300 mg/kg, p.o.), and CUMS+imipramine (15 mg/kg, p.o.), and treatment was given for seven consecutive days to the respective groups (day 29 to day 35). Behavioural parameters such as open field test, forced swim test, sucrose feeding test, and tail suspension test on day 1, day 28, and day 35 were measured, and biochemical parameters such as plasma corticosterone level, serotonergic system (5-HT, 5-HIAA, and 5-HT/5-HIAA), mitochondrial function, and proinflammatory mediators (TNF-α, IL-1ß, and IL-6) were estimated in hippocampus (HIP) and prefrontal cortex (PFC) regions of the brain on day 35, after the behavioural observations. On the other hand, phytochemical profile of Aegle marmelos was done. Results: On day 35, EAM (300 mg/kg) significantly reduced the immobility time during the tail suspension test from 208.66 ± 4.72 s to 108.83 ± 4.81 s and forced swim test from 200.16 ± 4.12 s to 148.5 ± 4.58 s. It also enhanced the behavioural parameters in the open field test such as ambulation from 26.5 ± 2.14 to 56.5 ± 1.80, rearing from 8.33 ± 0.71 to 19 ± 0.57, time spent in centre from 9.16 ± 0.9 to 17.16 ± 0.79 s, total distance travelled from 2.36 ± 0.12 to 4.68 ± 0.10 m, and anhedonia in the sucrose feeding test from 109.33 ± 1.08 to 135.83 ± 3.91 mL. The stimulation of the HPA axis resulting elevated corticosterone level caused by CUMS was reduced by EAM (300 mg/kg) from 80.12 ± 2.020 to 48.25 ± 2.407 µg/dL. Furthermore, EAM (300 mg/kg) increase CUMS-induced changes in serotonin (5-HT) level in HIP and PFC from 3.132 ± 0.09586 to 4.518 ± 0.1812 and 4.308 ± 0.1593 to 5.262 ± 0.1014 ng/mg protein, respectively. EAM (300 mg/kg) significantly attenuated the CUMS-induced changes in proinflammatory cytokine production and mitochondrial function in HIP and PFC. One group used to determine the acute toxicity as per OECD-23 standard protocol which resulted that 300 mg/kg EAM has no significant acute toxicity. Total phenolic content and total flavonoid content of standardized hydroalcoholic extract of AM was found 95.024 ± 2.431 and 36.820 ± 3.41, respectively, and additional identification tests showed the presence of alkaloids, tannins, saponins, cardiac glycosides, flavonoids, and terpenoids. Conclusion: On the basis of findings, EAM can be inferred as a potential antidepressant-like effect of this plan in preclinical research.

1,3,4-oxadiazole and its derivatives: A review on recent progress in anticancer activities.

The 1,3,4-oxadiazole nucleus is a biologically imperative scaffold possesses numerous biological activities. The broad and potent activity of 1,3,4-oxadiazole and their derivatives has established them as important pharmacological scaffolds especially in the treatment of cancer disease. Several di-, tri-, aromatic, and heterocyclic substituted 1,3,4-oxadiazole derivatives have been reported to possess potent anticancer activity. These substituted 1,3,4-oxadiazoles had shown different mechanism of action and participated in anticancer drug discovery and development. This review is complementary to earlier reviews and aims to review the work reported on anticancer activities of 1,3,4-oxadiazole derivatives from year 2000 to the beginning of 2020.

Anticancer Agents Based on Vulnerable Components in a Signalling Pathway.

Traditional cancer treatment includes surgery, chemotherapy, radiotherapy and immunotherapy that are clinically beneficial, but are associated with drawbacks such as drug resistance and side effects. In quest for better treatment, many new molecular targets have been introduced in the last few decades. Finding new molecular mechanisms encourages researchers to discover new anticancer agents. Exploring the mechanism of action also facilitates anticipation of potential resistance mechanisms and optimization of rational combination therapies. The write up describes the leading molecular mechanisms for cancer therapy, including mTOR, tyrosine Wee1 kinase (WEE1), Janus kinases, PI3K/mTOR signaling pathway, serine/threonine protein kinase AKT, checkpoint kinase 1 (Chk1), maternal embryonic leucine-zipper kinase (MELK), DNA methyltransferase I (DNMT1), poly (ADP-ribose) polymerase (PARP)-1/-2, sphingosine kinase-2 (SK2), pan-FGFR, inhibitor of apoptosis (IAP), murine double minute 2 (MDM2), Bcl-2 family protein and reactive oxygen species 1 (ROS1). Additionally, the manuscript reviews the anticancer drugs currently under clinical trials.

Anticancer Potential of Thiazole Derivatives: A Retrospective Review.

This review brings forth the potential of thiazole derivatives for their anticancer activities. The emphasis is placed on the structural diversity of thiazole derivatives, responsible for their specific anticancer activity. Multiple classes of thiazole derivatives such as Schiff base, mono-, di-, tri-, and heterocyclic substituents that possess anticancer activity have been exemplified. Molecular modelling of compounds that predicts enhanced anticancer activity of the modified structures has also been elaborated in the review. Significant advancements in synthetic chemistry related to cytotoxicity can now better position the drug discovery team to undertake thiazoles as valuable leads. The beneficial thiazole derivatives possessing anticancer activity will reignite the interest of medicinal chemists in thiazole and their derivatives.

Anticonvulsant evaluation of some newer benzimidazole derivatives: design and synthesis.

A series of new 2-[(1-substituted phenylethylidine) hydrazine]-N-phenyl-1H-benzo[d]imidazole-1-carbothioamides (4a-n) were designed and synthesized to have the pharmacophoric elements essential for anticonvulsant activity. The key step in the synthesis of the title compounds involves the reaction of 2-mercaptobenzimidazole with hydrazine hydrate, substituted acetophenones and phenylisothiocyanate to get the compounds in good yields. All the newly synthesized compounds were screened by two most adopted models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). Interestingly, compounds 4e, 4f, 4g, 4h and 4j exhibited potent anticonvulsant results and in the neurotoxicity screening, most of the compounds were devoid of toxicity at the dose of 60 and 100 mg/kg.

Microwave-assisted, solvent-free and parallel synthesis of some novel substituted imidazoles of biological interest.

Solvent free microwave assisted synthesis of some novel substituted imidazoles of biological interest is reported. First, primary aromatic or heteryl amine was condensed with aryl or heteryl aldehydes to afford corresponding Schiff's base. The Schiff's base further on treatment with ammonium acetate (NH(4)OAC) and isatin using silica gel as the solid support, yielded the corresponding aryl imidazoles. In this paper a comparative study between the developed microwave method and conventional method is described. The synthesized compounds were analyzed by physical and analytical data. The synthesized compounds were evaluated for their antibacterial, anthelmintic, short-term anticancer and antitubercular activity. All the synthesized substituted imidazoles have shown good antibacterial activity against gram negative bacterial strains Klebsiella pneumoniae and Escherichia coli and moderate to good anthelmintic activity. The synthesized imidazole derivative possessed significant cytotoxic activity against Ehrlich's ascites carcinoma (EAC) cell lines. None of the compounds exhibited prominent antitubercular activity.

Synthetic studies on novel benzimidazolopeptides with antimicrobial, cytotoxic and anthelmintic potential.

Four substituted benzimidazolyl-benzoic/salicylic acids 5-8 were synthesized by interaction of 5,6-dimethyl-/6-nitrobenzimidazoles with diazotized substituted/unsubstituted aminobenzoic acids in the presence of cupric chloride. The coupling of compounds 5-8 with different amino acid ester hydrochlorides/dipeptide/tripeptide/tetrapeptide methyl esters afforded novel benzimidazolopeptide derivatives 5a-f, 6a-h, 7a-g and 8a-g. The structures of all newly synthesized compounds were established on the basis of analytical, IR, (1)H NMR, (13)C NMR and mass spectral data. Selected peptide ester derivatives were further hydrolyzed by using lithium hydroxide (LiOH) to yield corresponding acid derivatives 5b(a)-d(a), 6e(a)-g(a), 7c(a)-e(a) and 8e(a)-g(a). All peptide derivatives were screened for their antimicrobial, anthelmintic and cytotoxic activities. Almost all newly synthesized benzimidazolopeptides have shown moderate to good anthelmintic activity against all three earthworm species and good antimicrobial activity against pathogenic fungal strains Candida albicans and Aspergillus niger, gram negative bacterial strains Pseudomonas aeruginosa and Escherichia coli. Compounds 8g and 8g(a) possessed significant cytotoxic activity against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines.

First total synthesis and biological screening of hymenamide E.

A new potent bioactive, proline-rich cyclic heptapeptide hymenamide E (13) was synthesized using the solution phase technique by cyclization of the linear peptide Boc-Phe-Pro-Thr-Thr-Pro-Tyr-Phe-OMe (12) after proper deprotection at carboxyl and amino terminals. Linear peptide segment was prepared by coupling the tripeptide unit Boc-Phe-Pro-Thr-OH (10a) with the tetrapeptide unit Thr-Pro-Tyr-Phe-OMe (11a) using dicyclohexylcarbodiimide as the coupling agent and N-methylmorpholine as the base. Structures of all new compounds were characterized by IR, 1H NMR spectral data as well as elemental analyses. In addition, the structure of compound 13 was verified by 13C NMR, fast atom bombardment mass spectroscopy and differential scanning calorimetry. The newly synthesized cyclopeptide was screened for its antibacterial, antifungal and anthelmintic activities against eight pathogenic microbes and two earthworm species. Compound 13 showed potent antifungal activity against Candida albicans and Ganoderma species comparable to that of griseofulvin as a reference drug and potent anthelmintic activity against earthworms Megascoplex konkanensis and Eudrilus species in comparison to piperazine citrate.