Advancements in liposomal formulations: A comprehensive exploration of industrial production techniques.

Liposomes are nanosized, spherical vesicles consisting of an aqueous core encircled by one or more phospholipid bilayer shells. Liposomes have found extensive use in numerous biomedicine and nanomedicine applications due to their excellent biocompatibility, adaptable chemical composition, ease of preparation, and diverse structural characteristics. These applications include nanocarriers for drug delivery, immunoassays, nutraceuticals, tissue engineering, clinical diagnostics, and theranostics formulations. These applications stimulated significant efforts toward scaling up formation processes in anticipation of appropriate industrial advancement. Despite the advancements in conventional methods and the emergence of new approaches for liposome production, their inherent susceptibility to chemical and mechanical influences contributes to critical challenges, including limited colloidal stability and decreased efficiency in encapsulating cargo molecules. With this context, the current review provides brief insights into liposomes conventional and novel industrial production techniques. With a special focus on the structural parameters, and pivotal elements influencing the synthesis of an appropriate and stable formulation, followed by the various regulatory aspects of industrial production.

Insights of biopolymeric blended formulations for diabetic wound healing.

Diabetic wounds (DWs) pose a significant health burden worldwide, with their management presenting numerous challenges. Biopolymeric formulations have recently gained attention as promising therapeutic approaches for diabetic wound healing. These formulations, composed of biocompatible and biodegradable polymers, offer unique properties such as controlled drug release, enhanced wound closure, and reduced scarring. In this review, we aim to provide a comprehensive overview of the current state of research and future prospects regarding the application of biopolymeric formulations for diabetic wound healing. The review begins by highlighting the underlying pathophysiology of DWs, including impaired angiogenesis, chronic inflammation, and compromised extracellular matrix (ECM) formation. It further explores the key characteristics of biopolymeric materials, such as their biocompatibility, biodegradability, and tunable physicochemical properties, which make them suitable for diabetic wound healing applications. The discussion further delves into the types of biopolymeric formulations utilized in the treatment of DWs. These include hydrogels, nanoparticles (NP), scaffolds, films, and dressings. Furthermore, the review addresses the challenges associated with biopolymeric formulations for diabetic wound healing. In conclusion, biopolymeric formulations present a promising avenue for diabetic wound healing. Their unique properties and versatility allow for tailored approaches to address the specific challenges associated with DWs. However, further research and developments are required to optimize their therapeutic efficacy, stability, manufacturing processes, and regulatory considerations. With continued advancements in biopolymeric formulations, the future holds great promise for improving the management and outcomes of DWs.

Exploring progress in iron supplement formulation approaches for treating iron deficiency anemia through bibliometric and thematic analysis.

Anemia is a severe health issue that affects around one-third of the global population. Therefore, the present study aims to conduct a bibliometric analysis to investigate the research trends regarding advancements on iron formulations in treating iron deficiency anemia via oral or parenteral route. This study adopts thematic and bibliometric methods on existing research on novel iron formulations. It also provides perspective into the existing understanding on treatment strategies for iron deficiency anemia. This study is conducted on 543 papers on various ferrous and ferric formulations used in the treatment of iron deficiency anemia. The study period is from 1977 to 2022, and the papers are identified from the Scopus database. The bibliometric analysis was carried out using the R tool's Bibliometrix package. The study discusses performance analysis, including annual publications, geographic analysis, relevant affiliations, journal analysis, and citation analysis. In addition, the conceptual structure, including the co-occurrence network, thematic map, thematic evolution, intellectual structure highlighting co-citation analysis, and social structure depicting the collaboration network and collaboration world map, are presented. The results showed increased research on formulation strategies for the treatment of iron deficiency anemia from 2010 onwards. The top 5 contributing countries are the USA, Italy, India, Germany, and the UK, and peer-reviewed journals from the area of nutrition. The most trending areas of study are iron deficiency anemia in pregnancy, chronic kidney diseases, inflammatory bowel diseases, and various intravenous formulations used in its treatment. The authors from Europe collaborate the most with authors from other countries. The study concludes that a safer and more effective iron formulation is needed to reduce the prevalence of anemia. The findings of the study are helpful in advancing research on innovative formulations for treating iron deficiency anemia. The insights from the study are helpful to policymakers in designing specific health policies and investing more in research and development of novel formulations for the treatment of iron deficiency anemia.

Hematopoietic cell kinase as a nexus for drug repurposing: implications for cancer and HIV therapy.

Hematopoietic cell kinase (HCK) has emerged as a potential target for therapeutic intervention in cancer and HIV infection because of its critical role in critical signaling pathways. Repurposing FDA-approved drugs offers an efficient strategy to identify new treatment options. Here, we address the need for novel therapies in cancer and HIV by investigating the potential of repurposed drugs against HCK. Our goal was to identify promising drug candidates with high binding affinities and specific interactions within the HCK binding pocket. We employed an integrated computational approach combining molecular docking and extensive molecular dynamics (MD) simulations. Initially, we analyzed the binding affinities and interaction patterns of a library of FDA-approved drugs sourced from DrugBank. After careful analysis, we focused on two compounds, Nilotinib and Radotinib, which exhibit exceptional binding affinities and specificity to the HCK binding pocket, including the active site. Additionally, we assessed the pharmacological properties of Nilotinib and Radotinib, making them attractive candidates for further drug development. Extensive all-atom MD simulations spanning 200 nanoseconds (ns) elucidated the conformational dynamics and stability of the HCK-Nilotinib and HCK-Radotinib complexes. These simulations demonstrate the robustness of these complexes over extended timescales. Our findings highlighted the potential of Nilotinib and Radotinib as promising candidates against HCK that offer valuable insights into their binding mechanisms. This computational approach provides a comprehensive understanding of drug interactions with HCK and sets the stage for future experimental validation and drug development endeavors.Communicated by Ramaswamy H. Sarma.

In-silico evaluation of Bismurrayaquinone-A phytochemical as a potential multifunctional inhibitor targeting dihydrofolate reductase: implications for anticancer and antibacterial drug development.

Dihydrofolate reductase (DHFR) has gained significant attention in drug development, primarily due to marked distinctions in its active site among different species. DHFR plays a crucial role in both DNA and amino acid metabolism by facilitating the transfer of monocarbon residues through tetrahydrofolate, which is vital for nucleotide and amino acid synthesis. This considers its potential as a promising target for therapeutic interventions. In this study, our focus was on conducting a virtual screening of phytoconstituents from the IMPPAT2.0 database to identify potential inhibitors of DHFR. The initial criterion involved assessing the binding energy of molecules against DHFR and we screened top 20 compounds ranging energy -13.5 to -11.4 (kcal/Mol) while Pemetrexed disodium bound with less energy -10.2 (kcal/Mol), followed by an analysis of their interactions to identify more effective hits. We prioritized IMPHY007679 (Bismurrayaquinone-A), which displayed a high binding affinity and crucial interaction with DHFR. We also evaluated the drug-like properties and biological activity of IMPHY007679. Furthermore, MD simulation was done, RMSD, RMSF, Rg, SASA, PCA and FEL explore the time-evolution impact of IMPHY007679 comparing it with a reference drug, Pemetrexed disodium. Collectively, our findings suggest that IMPHY007679 recommend further investigation in both in vitro and in vivo settings for its potential in developing anticancer and antibacterial therapies. This compound holds promise as a valuable candidate for advancing drug research and treatment strategies.Communicated by Ramaswamy H. Sarma.

PLGA nanomedical consignation: A novel approach for the management of prostate cancer.

The malignancy of the prostate is a complicated ailment which impacts millions of male populations around the globe. Despite the multitude of endeavour accomplished within this domain, modalities that are involved in the ameliorative management of predisposed infirmity are still relent upon non-specific and invasive procedures, thus imposing a detrimental mark on the living standard of the individual. Also, the orchestrated therapeutic interventions are still incompetent in substantiating a robust and unabridged therapeutic end point owing to their inadequate solubility, low bioavailability, limited cell assimilation, and swift deterioration, thereby muffling the clinical application of these existing treatment modalities. Nanotechnology has been employed in an array of modalities for the medical management of malignancies. Among the assortment of available nano-scaffolds, nanocarriers composed of a bio-decomposable and hybrid polymeric material like PLGA hold an opportunity to advance as standard chemotherapeutic modalities. PLGA-based nanocarriers have the prospect to address the drawbacks associated with conventional cancer interventions, owing to their versatility, durability, nontoxic nature, and their ability to facilitate prolonged drug release. This review intends to describe the plethora of evidence-based studies performed to validate the applicability of PLGA nanosystem in the amelioration of prostate malignancies, in conjunction with PLGA focused nano-scaffold in the clinical management of prostate carcinoma. This review seeks to explore numerous evidence-based studies confirming the applicability of PLGA nanosystems in ameliorating prostate malignancies. It also delves into the role of PLGA-focused nano-scaffolds in the clinical management of prostate carcinoma, aiming to provide a comprehensive perspective on these advancements.

Hesperidin-loaded cubogel as a novel therapeutic armamentarium for full-thickness wound healing.

Wounds are a physical manifestation of injury to the skin causing it to rupture or tear. The process of wound healing naturally restores skin integrity while minimizing the extent of the damage. Hesperidin (HPN) is a natural polyphenolic flavonoid and is effective in treating wounds due to its ability to reduce inflammation and stimulate angiogenesis. However, its use is limited by its poor physicochemical attributes such as poor solubility in water. Recently, nanoparticles, particularly Cubosomes, are found to be promising candidates for advancing wound-healing therapies, owing to their unique properties. The present study was conducted to develop a hydrogel system based on Cubosomes encapsulating HPN (HPN-Cubogel), with the potential to mitigate full-thickness wounds. The therapeutic efficacy of the formulation assessed in the animal model showed that the HPN-Cubogel formulation group exhibited a wound closure rate of 98.96 ± 1.50% after 14 days post-wounding compared to 89.12 ± 2.6% in the control group suggesting superior wound contraction activity. Collagen synthesis was superior in the formulation compared to the control group, as determined through MT staining. In summary, the HPN-Cubogel formulation was found to be the most effective in enhancing full-thickness wound healing.

Targeting Sirtuin 1 for therapeutic potential: Drug repurposing approach integrating docking and molecular dynamics simulations.

Identifying novel therapeutic agents is a fundamental challenge in contemporary drug development, especially in the context of complex diseases like cancer, neurodegenerative disorders, and metabolic syndromes. Here, we present a comprehensive computational study to identify potential inhibitors of SIRT1 (Sirtuin 1), a critical protein involved in various cellular processes and disease pathways. Leveraging the concept of drug repurposing, we employed a multifaceted approach that integrates molecular docking and molecular dynamics (MD) simulations to predict the binding affinities and dynamic behavior of a diverse set of FDA-approved drugs from DrugBank against the SIRT1. Initially, compounds were shortlisted based on their binding affinities and interaction analyses to identify safe and promising binding partners for SIRT1. Among these candidates, Doxercalciferol and Timiperone emerged as potential candidates, displaying notable affinity, efficiency, and specificity towards the binding pocket of SIRT1. Extensive evaluation revealed that these identified compounds boast a range of favorable biological properties and prefer binding to the active site of SIRT1. To delve deeper into the interactions, all-atom MD simulations were conducted for 500 nanoseconds (ns). These simulations assessed the conformational dynamics, stability, and interaction mechanism of the SIRT1-Doxercalciferol and SIRT1-Timiperone complexes. The MD simulations illustrated that the SIRT1-Doxercalciferol and SIRT1-Timiperone complexes maintain stability over a 500 ns trajectory. These insightful outcomes propose that Doxercalciferol and Timiperone hold promise as viable scaffolds for developing potential SIRT1 inhibitors, with implications for tackling complex diseases such as cancer, neurodegenerative disorders, and metabolic syndromes.

Potential Pharmacological Applications of Nigella Seeds with a Focus on Nigella sativa and Its Constituents against Chronic Inflammatory Diseases: Progress and Future Opportunities.

The leading cause of death worldwide has been identified as chronic illnesses, according to the World Health Organization (WHO). Chronic inflammatory conditions such as asthma, cancer, diabetes, heart disease, and obesity account for three out of every five deaths. Although many people benefit from using nonsteroidal anti-inflammatory medicines (NSAIDs) for pain and inflammation relief, there are significant adverse effects to using these medications. Medicinal plants possess anti-inflammatory properties with minimal or no side effects. Nigella sativa (NS), also known as black cumin, is one of the plants used in traditional medicine the most. Many studies on the NS have shown that their therapeutic properties are attributed to the seed, oil, and secondary metabolites. This plant has been studied extensively and has many medical uses, such as anti-inflammatory. NS or its phytochemical compounds, such as thymoquinone, can cause cell apoptosis via oxidative stress, block efflux pumps, enhance membrane permeability, and exert potent biocidal effects. Notwithstanding the extensively documented anti-inflammatory effectiveness observed in the experimental model, the precise mechanisms underlying its anti-inflammatory effects in diverse chronic inflammatory diseases and its multi-targeting characteristics remain largely unexplored. This review examines NS or its secondary metabolites, a valuable source for the therapeutic development of chronic inflammatory diseases. Most clinical studies were done for diabetes and cardiovascular disease; therefore, more studies are required to examine the NS extracts and phytoconstituents to treat cancer, obesity, diabetes, asthma, neurological disorders, and COVID-19. This study will be a significant resource for clinicians and biologists seeking a pharmaceutical solution for inflammatory diseases.

Prediction of molecular interaction of Phosphodiesterase 10A inhibition by natural compounds: insights from structure-based screening and molecular dynamics simulations.

Phosphodiesterase 10 A (PDE10A) is an enzyme that regulates cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels in the brain, particularly in the striatum, which plays a critical role in movement control and reward processing. Inhibition of PDE10A can increase cAMP and cGMP levels, improving neuronal signaling and reducing symptoms of neuropsychiatric disorders such as schizophrenia, Huntington's disease, and Parkinson's disease. In this study, a structure-based virtual screening was conducted to identify potential anti-neuropsychiatric disorders compounds from phytoconstituents in the IMPPAT database. The ligands were docked against PDE10A, resulting in 40 compounds with appreciable docking scores. These 40 compounds underwent further ADMET predictions and drug likeliness, resulting in five potential compounds. Finally, based on the specific interactions, two compounds (Colladonin and Isopongachromene), were subjected to molecular dynamics (MD) simulation and MM-PBSA studies. The MM-PBSA analysis validated and captured the intermolecular interactions, indicating that Colladonin and Isopongachromene had appreciable binding affinities of -155.60 kJ.mol-1 and -108.28 kJ.mol-1, respectively and were promising candidates against neuropsychiatric disorders, targeting PDE10A. Overall, this study provides insight into the potential of PDE10A inhibitors as therapeutic agents for treating neuropsychiatric disorders, and Colladonin and Isopongachromene are promising compounds for further development.Communicated by Ramaswamy H. Sarma.

Insight into the Biological Roles and Mechanisms of Phytochemicals in Different Types of Cancer: Targeting Cancer Therapeutics.

Cancer is a hard-to-treat disease with a high reoccurrence rate that affects health and lives globally. The condition has a high occurrence rate and is the second leading cause of mortality after cardiovascular disorders. Increased research and more profound knowledge of the mechanisms contributing to the disease's onset and progression have led to drug discovery and development. Various drugs are on the market against cancer; however, the drugs face challenges of chemoresistance. The other major problem is the side effects of these drugs. Therefore, using complementary and additional medicines from natural sources is the best strategy to overcome these issues. The naturally occurring phytochemicals are a vast source of novel drugs against various ailments. The modes of action by which phytochemicals show their anti-cancer effects can be the induction of apoptosis, the onset of cell cycle arrest, kinase inhibition, and the blocking of carcinogens. This review aims to describe different phytochemicals, their classification, the role of phytochemicals as anti-cancer agents, the mode of action of phytochemicals, and their role in various types of cancer.

Inhibition of microtubule affinity regulating kinase 4 by an acetylcholinesterase inhibitor, Huperzine A: Computational and experimental approaches.

Microtubule affinity regulating kinase 4 (MARK4), 752 amino acids long, belonging to the AMPK superfamily, plays a vital role in regulating microtubules due to its potential to phosphorylate microtubule-associated proteins (MAP's) and thus, MARK4 plays a key role in Alzheimer's disease (AD) pathology. MARK4 is a druggable target for cancer, neurodegenerative diseases, and metabolic disorders. In this study, we have evaluated the MARK4 inhibitory potential of Huperzine A (HpA), an acetylcholinesterase inhibitor (AChEI), a potential AD drug. Molecular docking revealed the key residues governing the MARK4-HpA complex formation. The structural stability and conformational dynamics of the MARK4-HpA complex was assessed by employing Molecular dynamics (MD) simulation. The results suggested that the binding of HpA with MARK4 leads to minimal structural alterations in the native conformation of MARK4, implying the stability of the MARK4-HpA complex. Isothermal titration calorimetry (ITC) studies deciphered that HpA binds to MARK4 spontaneously. Moreover, the kinase assay depicted significant inhibition of MARK by HpA (IC50 = 4.91 µM), implying it to be a potent MARK4 inhibitor that can be implicated in the treatment of MARK4-directed diseases.

A cross-sectional study on Saudi pharmacists working as medical representatives: What attracted them and what is keeping them in this sector-Misconceptions and reality.

Background: The government in Saudi Arabia issued a labor reform initiative to renationalize the pharmacy profession in pharmaceutical companies to generate more employment for Saudi pharmacists. Considering the nationalization of the pharmacy workforce employed in this sector, as well as the pharmacists' preferences toward working in this setting, the current study was conducted determine the reasons to choose this career pathway, to clarify the common misconceptions about this sector and to assess job satisfaction, work commitment, and intentions to leave. Methods: An online self-administered questionnaire was used to collect data from pharmacists working as medical representatives across Saudi Arabia. A total of 133 medical representatives participated in the study. Results: The main factors that motivated study participants to join this sector included performing a socially important job, receiving a high salary, and further career development. The common misconceptions about the sector, such as lacking honor and value and considering commercial values to be accepted, were found to be incorrect by the medical representatives. A high job satisfaction level, high work commitment, and low intentions to leave the sector were reported by participants. Conclusion: Working as a medical representative in a pharmaceutical company is an appealing career choice that fulfills pharmacists' career ambitions and may help in creating more jobs for the increasing numbers of pharmacy graduates.

Wound healing properties of a new formulated flavonoid-rich fraction from Dodonaea viscosa Jacq. leaves extract.

Background: Dodonaea viscosa Jacq. (D. viscosa) belongs to the family of Sapindaceae, commonly known as "Sinatha," and is used as a traditional medicine for treating wounds due to its high flavonoids content. However, to date there is no experimental evidence on its flavonoid-rich fraction of D. viscosa formulation as an agent for healing wounds. Objective: The present study aimed to evaluate the wound healing effect of ethyl acetate fraction of D. viscosa leaves on dermal wounds. Methods: The ethyl acetate fraction was produced from a water-ethanol extract of D. viscosa leaves and was quantitatively evaluated using the HPLC technique. The in-vivo wound healing ability of the ethyl acetate fraction of D. viscosa ointment (DVFO, 2.5%w/w and 5%w/w) was investigated in Sprague-Dawley rats utilizing an incision and excision paradigm with povidone-iodine ointment (5% w/w) as a control. The percentage of wound closure, hydroxyproline and hexosamine concentrations, tensile strength and epithelialization duration were measured. Subsequently, histopathology analysis of skin samples as well as western blots were performed for collagen type 3 (COL3A1), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Results: The ethyl acetate fraction of D. viscosa revealed flavonoids with high concentrations of quercetin (6.46% w/w) and kaempferol (0.132% w/w). Compared to the control group, the DVFO (2.5% and 5.0% w/w) significantly accelerated wound healing in both models, as demonstrated by quicker wound contraction, epithelialization, elevated hydroxyproline levels and increased tensile strength. Histopathological investigations also revealed that DVFO treatment improved wound healing by re-epithelialization, collagen formation and vascularization of damaged skin samples. Western blot analysis further demonstrated an up-regulation of COL3A, vascular endothelial growth factor and bFGF protein in wound granulation tissue of the DVFO-treated group (p < 0.01). Conclusion: It is concluded that flavonoid-rich D. viscosa ethyl acetate fraction promotes wound healing by up-regulating the expressions of COL3A, VEGF and bFGF protein in wound granulation tissue. However, extensive clinical and pre-clinical research on the flavonoid-rich fraction of D. viscosa is needed to determine its significant impact in the healing of human wounds.

Linagliptin and Empagliflozin Inhibit Microtubule Affinity Regulatory Kinase 4: Repurposing Anti-Diabetic Drugs in Neurodegenerative Disorders Using In Silico and In Vitro Approaches.

Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are significant public health burdens. Many studies have revealed the possibility of common pathophysiology between T2DM and AD. Thus, in recent years, studies deciphering the action mechanism of anti-diabetic drugs with their future use in AD and related pathologies are on high demand. Drug repurposing is a safe and effective approach owing to its low cost and time-saving attributes. Microtubule affinity regulating kinase 4 (MARK4) is a druggable target for various diseases and is found to be linked with AD and diabetes mellitus. MARK4 plays a vital role in energy metabolism and regulation and thus serves as an irrefutable target to treat T2DM. The present study was intended to identify the potent MARK4 inhibitors among FDA-approved anti-diabetic drugs. We performed structure-based virtual screening of FDA-approved drugs to identify the top hits against MARK4. We identified five FDA-approved drugs having an appreciable affinity and specificity toward the binding pocket of MARK4. Among these identified hits, two drugs, linagliptin, and empagliflozin, favorably bind to the MARK4 binding pocket, interacting with its critical residues and thus subjected to detailed analysis. All-atom detailed molecular dynamics (MD) simulations revealed the dynamics of binding of linagliptin and empagliflozin with MARK4. Kinase assay showed significant inhibition of MARK4 kinase activity in the presence of these drugs, implying them as potent MARK4 inhibitors. In conclusion, linagliptin and empagliflozin may be promising MARK4 inhibitors, which can further be exploited as potential lead molecules against MARK4-directed neurodegenerative diseases.

Anti-Tumor Potential of Gymnema sylvestre Saponin Rich Fraction on In Vitro Breast Cancer Cell Lines and In Vivo Tumor-Bearing Mouse Models.

Gymnema sylvestre (GS) is a perennial woody vine native to tropical Asia, China, the Arabian Peninsula, Africa and Australia. GS has been used as a medicinal plant with potential anti-microbial, anti-inflammatory and anti-oxidant properties. This study was conceptualized to evaluate the cytotoxicity potential of Gymnema sylvestre saponin rich fraction (GSSRF) on breast cancer cell lines (MCF-7 and MDA-MB-468) by SRB assay. The anti-tumor activity of GSSRF was assessed in tumor-bearing Elrich ascites carcinoma (EAC) and Dalton's lymphoma ascites (DLA) mouse models. The anti-oxidant potential of GSSRF was assessed by DPPH radical scavenging assay. The acute toxicity of GSSRF was carried out according to OECD guideline 425. The yield of GSSRF was around 1.4% and the presence of saponin content in GSSRF was confirmed by qualitative and Fourier transform infrared spectroscopic (FTIR) analysis. The in vitro cytotoxic effects of GSSRF on breast cancer cell lines were promising and found to be dose-dependent. An acute toxicity study of GSSRF was found to be safe at 2000 mg/kg body weight. GSSRF treatment has shown a significant increase in the body weight and the life span of EAC-bearing mice in a dose-dependent manner when compared with the control group. In the solid tumor model, the doses of 100 and 200 mg/kg body weight per day have shown about 46.70% and 60.80% reduction in tumor weight and controlled the tumor weight until the 30th day when compared with the control group. The activity of GSSRF in both models was similar to the cisplatin, a standard anticancer agent used in the study. Together, these results open the door for detailed investigations of anti-tumor potentials of GSSRF in specific tumor models, mechanistic studies and clinical trials leading to promising novel therapeutics for cancer therapy.

Role of lisinopril in the therapeutic management of cardiovascular disease by targeting microtubule affinity regulating kinase 4: molecular docking and molecular dynamics simulation approaches.

Cardiovascular diseases (CVDs) are a major cause of premature adult death. Various factors contribute to the development of CVDs, such as atherosclerosis leading to myocardial infarction (MI), and compromised cardiac function after MI leads to chronic heart failure with systemic health complications and a high mortality rate. Microtubule detyrosination has rapidly evolved as an essential mechanism to regulate cardiomyocyte contractility. Microtubule affinity regulating kinase 4 (MARK4) regulates cardiomyocyte contractility in a way that it promotes phosphorylation of microtubule-associated protein 4, thereby facilitating the access of vasohibin 2-a tubulin carboxypeptidase-to microtubules for the detyrosination of α-tubulin. Lisinopril, a drug belonging to the class of angiotensin-converting enzyme inhibitors, is used to treat high blood pressure. This is also used to treat heart failure, which plays a vital role in improving the survival rate post-heart attack. In this study, we will evaluate the MARK4 inhibitory potential of lisinopril employing molecular docking and molecular dynamics (MD) simulation approaches. Molecular docking analysis suggested that lisinopril binds to MARK4 with a significant binding affinity forming interactions with functionally essential residues of MARK4. Additionally, MD simulation deciphered the structural dynamics and stability of the MARK4-lisinopril complex. The findings of MD studies established that minimal structural deviations are observed during simulation, affirming the stability of the MARK4-lisinopril complex. Altogether, this study demonstrates lisinopril's crucial role in the therapeutic management of CVD by targeting MARK4.Communicated by Ramaswamy H. Sarma.

Pharmacological and Clinical Efficacy of Picrorhiza kurroa and Its Secondary Metabolites: A Comprehensive Review.

Traditional remedies for the treatment of various ailments are gaining popularity. Traditionally, one of the most valuable therapeutic herbs has been Picrorhiza kurroa Royle ex Benth. Traditional and folk uses of P. kurroa include chronic constipation, skin-related problems, burning sensation, chronic reoccurring fever, jaundice, heart problems, breathing, digestion, allergy, tuberculosis, blood-related problems, prediabetes and obesity, laxative, cholagogue, and liver stimulatory. Phytoconstituents such as glycosides, alkaloids, cucurbitacins, iridoids, phenolics, and terpenes in P. kurroa have shown promising pharmacological potential. In order to uncover novel compounds that may cure chronic illnesses, such as cardiovascular, diabetes, cancer, respiratory, and hepatoprotective diseases, the screening of P. kurroa is essential. This study comprehensively evaluated the ethnopharmacological efficacy, phytochemistry, pharmacological activity, dose, and toxicity of P. kurroa. This review provides comprehensive insights into this traditional medication for future research and therapeutic application. The purpose of this review article was to determine the pharmacological effects of P. kurroa on a variety of disorders. P. kurroa may be a natural alternative to the standard treatment for eradicating newly evolving diseases. This study is intended as a resource for future fundamental and clinical investigations.

In Vitro, Molecular Docking and In Silico ADME/Tox Studies of Emodin and Chrysophanol against Human Colorectal and Cervical Carcinoma.

Anthraquinones (AQs) are present in foods, dietary supplements, pharmaceuticals, and traditional treatments and have a wide spectrum of pharmacological activities. In the search for anti-cancer drugs, AQ derivatives are an important class. In this study, anthraquinone aglycons chrysophanol (Chr), emodin (EM) and FDA-approved anticancer drug fluorouracil were analyzed by molecular docking studies against receptor molecules caspase-3, apoptosis regulator Bcl-2, TRAF2 and NCK-interacting protein kinase (TNIK) and cyclin-dependent protein kinase 2 (CDK2) as novel candidates for future anticancer therapeutic development. The ADMET SAR database was used to predict the toxicity profile and pharmacokinetics of the Chr and EM. Furthermore, in silico results were validated by the in vitro anticancer activity against HCT-116 and HeLa cell lines to determine the anticancer effect. According to the docking studies simulated by the docking program AutoDock Vina 4.0, Chr and EM had good binding energies against the target proteins. It has been observed that Chr and EM show stronger molecular interaction than that of the FDA-approved anticancer drug fluorouracil. In the in vitro results, Chr and EM demonstrated promising anticancer activity in HCT-116 and HeLa cells. These findings lay the groundwork for the potential use of Chr and EM in the treatment of human colorectal and cervical carcinomas.

The Structural, Biological, and In-Silico Profiling of Novel Capryloyl Tetra-Glucoside and Aliphatic Ester Constituents from the Abutilon indicum Offers New Perspectives on the Treatment of Pain and Inflammation.

Abutilon indicum L. (Malvaceae), more often referred to as Peeli booti, Kanghi, and Kakhi, is a perennial shrub found in many countries of Asia. Traditionally, this plant is used as a diuretic to treat inflammation, discomfort, urethral infections, and gout. Inflammation and pain are key topics of interest for researchers throughout the globe, since they are linked to almost every illness that could affect humans or animals. The present study was conducted to isolate the phytoconstituents from the methanolic extract of Abutilon indicum collected from the Bihar state Koshi river belt in India, and to evaluate the isolated phytoconstituents' ability to reduce nociception and inflammation. Furthermore, molecular docking was performed to investigate the molecular interaction profile, with possible therapeutic targets for anti-inflammatory medicines. A. indicum methanolic extract yielded two novel phytocompounds identified as 5'-hydroxyhexyl n-hexadecanoate (AB-01) and n-octanoyl-ß-D-glucopyranosyl-(2'-1'')-ß-D-glucopyranosyl-(2''-1''')-ß-D-glucopyranosyl-(2'''-1'''')-ß-D-glucopyranoside (AB-05), together with three previously recognized phytocompounds such as ester glucoside. All isolated molecules were tested for the efficacy of analgesic and anti-inflammatory characteristics at doses of 5 and 10 mg/kg body weight. The isolated compound's molecular interaction profile with anti-inflammatory drug targets cyclooxygenase-2 and tumor necrosis factor-alpha possessed high potential energy in molecular docking. These findings may aid in developing anti-inflammatory and analgesic drugs from A. indicum.