The Potential of Natural Products in the Management of Cardiovascular Disease.

Cardiovascular Disease (CVD) is one of the most prevalent diseases in the world, comprising a variety of disorders such as hypertension, heart attacks, Peripheral Vascular Disease (PVD), dyslipidemias, strokes, coronary heart disease, and cardiomyopathies. The World Health Organization (WHO) predicts that 22.2 million people will die from CVD in 2030. Conventional treatments for CVDs are often quite expensive and also have several side effects. This potentiates the use of medicinal plants, which are still a viable alternative therapy for a number of diseases, including CVD. Natural products' cardio-protective effects result from their anti-oxidative, anti-hypercholesterolemia, anti-ischemic, and platelet aggregation-inhibiting properties. The conventional therapies used to treat CVD have the potential to be explored in light of the recent increase in the popularity of natural goods and alternative medicine. Some natural products with potential in the management of cardiovascular diseases such as Allium sativum L., Ginkgo biloba, Cinchona ledgeriana, Ginseng, Commiphora mukul, Digitalis lanata, Digitalis purpurea L., Murrayakoenigii, Glycyrrhiza glabra, Polygonum cuspidatum, Fenugreek, Capsicum annuum, etc. are discussed in this article.

Exploring the Potential of Essential Oil from Plectranthus amboinicus Leaves against Breast Cancer: In vitro and In silico Analysis.

Plectranthus amboinicus leaves were subjected to hydrodistillation to obtain essential oil (EO). Phytochemical analysis using gas chromatography-mass spectrometry revealed a diverse range of compounds in the EO, with p-cymen-4-ol (18.57%) emerging as the most predominant, followed by isocaryophyllene (12.18%). The in vitro antiproliferative activity of EO against breast cancer was assessed in MCF-7 and MDA-MB-231 cell lines. The MTT assay results revealed that EO showed IC50 values of 42.25 µg/mL and 13.44 µg/mL in MCF-7 cells and 63.67 µg/mL and 26.58 µg/mL in MDA-MB-231 cells after 24 and 48 h, respectively. The in silico physicochemical and pharmacokinetic profiles of the EO constituents were within acceptable limits. Molecular docking was conducted to investigate the interactions between the constituents of the EO and protein Aromatase (PDB ID:3S79). Among the EO constituents, 4-tert-butyl-2-(5-tert-butyl-2-hydroxyphenyl)phenol (4BHP) exhibited the highest dock score of -6.580 kcal/mol when compared to the reference drug, Letrozole (-5.694 kcal/mol), but was slightly lesser than Anastrozole (-7.08 kcal/mol). Molecular dynamics simulation studies (100 ns) of the 4BHP complex were performed to study its stability patterns. The RMSD and RMSF values of the 4BHP protein complex were found to be 2.03 Å and 4.46 Å, respectively. The binding free energy calculations revealed that 4BHP displayed the highest negative binding energy of -43 kcal/mol with aromatase protein, compared to Anastrozole (-40.59 kcal/mol) and Letrozole (-44.54 kcal/mol). However, further research is required to determine the safety, efficacy, and mechanism of action of the volatile oil. Taking into consideration the key findings of the present work, the development of a formulation of essential oil remains a challenging task and novel drug delivery systems may lead to site-specific and targeted delivery for the effective treatment of breast cancer.

An Update on Pharmacological and Phytochemical Aspects of Costus pictus D. Don - A Promising Anti-diabetic Plant.

BACKGROUND: The genus Costus is the largest genus in the family Costaceae and encompasses about 150 known species. Among these, Costus pictus D. Don (Synonym: Costus mexicanus) is a traditional medicinal herb used to treat diabetes and other ailments. Currently, available treatment options in modern medicine have several adverse effects. Herbal medicines are gaining importance as they are cost-effective and display improved therapeutic effects with fewer side effects. Scientists have been seeking therapeutic compounds in plants, and various in vitro and in vivo studies report Costus pictus D. Don as a potential source in treating various diseases. Phytochemicals with various pharmacological properties of Costus pictus D. Don, viz. anticancer, anti-oxidant, diuretic, analgesic, and anti-microbial have been worked out and reported in the literature. OBJECTIVE: The aim of the review is to categorize and summarize the available information on phytochemicals and pharmacological properties of Costus pictus D. Don and suggest outlooks for future research. METHODS: This review combined scientific data regarding the use of Costus pictus D. Don plant for the management of diabetes and other ailments. A systematic search was performed on Costus pictus plant with anti-diabetic, anti-cancer, anti-microbial, anti-oxidant, and other pharmacological properties using several search engines such as Google Scholar, PubMed, Science Direct, SciFinder, other online journals and books for detailed analysis. RESULTS: Research data compilation and critical review of the information would be beneficial for further exploration of its pharmacological and phytochemical aspects and, consequently, new drug development. Bioactivity-guided fractionation, isolation, and purification of new chemical entities from the plant as well as pharmacological evaluation of the same will lead to the search for safe and effective novel drugs for better healthcare. CONCLUSION: This review critically summarizes the reports on natural compounds, and different extract of Costus pictus D. Don with their potent anti-diabetic activity along with other pharmacological activity. Since this review has been presented in a very interactive manner showing the geographical region of availability, parts of plant used, mechanism of action and phytoconstituents in different extracts of Costus pictus responsible for particular action, it will be of great importance to the interested readers to focus on the development of the new drug leads for the treatment of diseases.

Exploring the Promising Role of Guggulipid in Rheumatoid Arthritis Management: An In-depth Analysis.

BACKGROUND: Guggulipid, an oleo-gum resin extracted from the bark of Commiphora wightii of the Burseraceae family, holds a significant place in Ayurvedic medicine due to its historical use in treating various disorders, including inflammation, gout, rheumatism, obesity, and lipid metabolism imbalances. OBJECTIVE: This comprehensive review aims to elucidate the molecular targets of guggulipids and explore their cellular responses. Furthermore, it summarizes the findings from in-vitro, in-vivo, and clinical investigations related to arthritis and various inflammatory conditions. METHODS: A comprehensive survey encompassing in-vitro, in-vivo, and clinical studies has been conducted to explore the therapeutic capacity of guggulipid in the management of rheumatoid arthritis. Various molecular pathways, such as cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), PI3-kinase/AKT, JAK/STAT, nitric oxide synthase (iNOS), and NFκB signaling pathways, have been targeted to assess the antiarthritic and anti-inflammatory effects of this compound. RESULTS: The research findings reveal that guggulipid demonstrates notable antiarthritic and anti-inflammatory effects by targeting key molecular pathways involved in inflammatory responses. These pathways include COX-2, VEGF, PI3-kinase/AKT, JAK/STAT, iNOS, and NFκB signaling pathways. in-vitro, in-vivo, and clinical studies collectively support the therapeutic potential of guggulipid in managing rheumatoid arthritis and related inflammatory conditions. CONCLUSION: This review provides a deeper understanding of the therapeutic mechanisms and potential of guggulipid in the management of rheumatoid arthritis. The collective evidence strongly supports the promising role of guggulipid as a therapeutic agent, encouraging further research and development in guggulipid-based treatments for these conditions.

Advances in Nanogel as Drug Delivery System for Cancer Therapeutics: An Overview.

Nanogels have gotten much attention as nanoscopic drug carriers, especially for delivering bioactive mediators to specific sites or at certain times. The versatility of polymer systems and the ease with which their physicochemical properties can be changed have resulted in versatile nano gel formulations. Nanogels offer exceptional stability, drug-loading capacity, biological consistency, strong penetration ability, and the ability to respond to environmental stimuli. Nanogels have shown great promise in various sectors, including gene delivery, chemotherapeutic medication delivery, diagnostics, organ targeting, and many more. This review focuses on various types of nanogels, preparation methods, including drug loading methods, various modes of biodegradation mechanisms, and primary mechanisms of drug release from nanogels. The article also focuses on the historical data for herb-related nanogels that are used to treat various disorders with great patient compliance, delivery rate, and efficacy.

Exploring sodium glucose cotransporter (SGLT2) inhibitors with machine learning approach: A novel hope in anti-diabetes drug discovery.

Conventional anti-diabetes agents exhibit some undesirable side effects. Recently, lactic acidosis and/or bladder cancer were also reported with the use of these agents. Hence, there is an urgent need for alternative anti-diabetes in order to reduce/avoid the unwanted effects. In this scenario sodium glucose cotransporter 2 (SGLT2) inhibitors has already been established as an important class of anti-diabetic drug. The search for new generation SGLT2 inhibitors with high affinity is still an ongoing process. Here, we aim to develop computational models to predict the SGLT2 inhibitory activity of small molecules based on chemical structures. This work provides in-silico analysis to propose possible fragment/fingerprint identification recommended for SGLT2 inhibitors. Up-to-our knowledge, this study is an initiative to propose fingerprints responsible for SGLT2 inhibition. Furthermore, we used nine different algorithms to build machine learning (ML) models that could be used to prioritize compounds as SGLT2 inhibitors from large libraries. The best performing ML models were applied to virtually screen a large collection of FDA approved drugs. The best predicted compounds have been recommended to be biologically investigated in future in order to identify next generation SGLT2 inhibitors with different chemical structure.

Identification of structural requirements and prediction of inhibitory activity of natural flavonoids against Zika virus through molecular docking and Monte Carlo based QSAR Simulation.

There has been growing interest in the research of flavonoids due to their potential antiviral activities. Recently, some natural flavonoids have shown potential inhibitory activity against zika virus NS3-NS2B protease. In order to accelerate the drug discovery efforts using flavonoids, a Monte Carlo simulation-based QSAR method has been applied to find out the structural requirements for the inhibitory activity. The best QSAR model was obtained using SMILES descriptors and HSG descriptors with 1EC connectivity with the following statistical parameters: R 2 = 0.9569 and Q 2 = 0.9050 for the test set. The best model was further utilised for the prediction of inhibitory activity of some other natural flavonoids. Four flavonoids (amentoflavone, fisetin, isorhamnetin and theaflavin-3-gallate) have shown higher predicted inhibitory activity and further validated by performing docking analysis. This study may help in understanding and performing natural flavonoids-based drug discovery against zika virus.

Design, synthesis and biological evaluation of some novel benzimidazole derivatives for their potential anticonvulsant activity.

Selective GABA(A) receptor ligands are widely used clinically to reduce the occurrence of convulsions. Hence there is an intense interest in developing new benzimidazole derivatives demonstrating high selectivity and high affinity for GABA(A) receptors. With the purpose of designing new chemical entities with an enhanced binding affinity for GABA(A)/BZd receptor complex, we carried out a QSAR study on benzotriazine derivatives. We studied 28 potent GABA(A) receptor ligands; derivatives of benzotriazines, using a combination of various tested physicochemical, steric, electronic and thermodynamic descriptors to determine the quantitative correlation between binding affinity and structural features. The developed and validated final model showed a good correlative and predictive ability expressed by a squared correlation co-efficient (r(2)) of 0.954. The equation indicated that the binding affinity is strongly dependent upon the thermodynamic properties (CDE, DDE and PC). Correlation between these properties and anticonvulsant activity was used to synthesize compounds possessing potent anticonvulsant activity. Most of the compounds showed an ability to inhibit the maximum electroshock (MES) and pentylenetetrazole (PTZ)-induced convulsions. Compound 1A, i.e. 2-(4-Chloro-phenyl)-5-nitro-1H-benzimidazole exhibited maximum activity in both the convulsion models.