In Silico Prediction and Pharmacokinetic Comparison of Ursodeoxycholic Acid and Obeticholic Acid in the Management of Primary Biliary Cholangitis

Background: Primary Biliary Cholangitis (PBC) is a persistent liver disease. Ursodeoxycholic acid is used as a first-line treatment for the past two decades. However, concurrent use of Ursodeoxycholic acid reported with a severe adverse drug reaction. Obeticholic acid has been started utilizing as monotherapy and also with Ursodeoxycholic acid in a patient who is intolerant to Ursodeoxycholic acid therapy. We primarily aimed to compare the pharmacokinetic & toxicity profiles of Ursodeoxycholic acid and Obeticholic acid using in silico methods. Method: The pharmacokinetic profile of UDCA & OCA was observed from PKCSM server online database, OSIRIS® property Explorer, T.E.S.T. (Toxicity estimation software tool) & Molinspiration® is used to estimate the drug toxicity profiles. Result: This computer-aided response provides a great understanding and creates a gap between the theoretical and clinical evidence for UDCA & OCA's preference in PBC management. Conclusion: Co-administration of Obeticholic acid with Ursodeoxycholic acid will be an effective treatment for PBC in patients with UDCA intolerants. However, both medications are well-recognized substrates of the CYP3A4 enzyme and may lead to unintended drug interactions and side effects. Keywords: Primary Biliary Cholangitis, Obeticholic acid, Ursodeoxycholic acid, CYP3A4, Drug Interactions, Pharmacokinetics

Necessity of Herbal Medicine in the Management of Metabolic Syndrome

People are more susceptible to a variety of diseases based on their lifestyle and occupational patterns. Metabolic syndrome (MS) is a worldwide health issue that is linked to a variety of risk factors, including hyperglycemia, dyslipidemia, hypertension, and obesity. Herbal medicine has been used for a long time. Herbal medicines have emerged as a significant source and major focus for future drug development and human health care. Botanicals may be useful for treating or preventing metabolic syndrome because they often have a wide range of biologically active compounds that can work together to boost each other’s effectiveness or have a synergistic effect, giving more benefit than a single chemical substance. Some extracts of botanicals frequently contain natural active components that act on multiple biological targets, creating an opportunity to concurrently resolve multiple defects associated with metabolic syndrome. To find out if botanicals can be used to treat metabolic syndrome as a group, trials must be stratified to look at differences in disease severity, age, gender, and genetic variation in the sample populations

Synthesis of quercetin–iron (Fe) complex and its in silico and in vitro confirmation towards antibacterial activity

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Network pharmacology based pharmacokinetic assessment and evaluation of the therapeutic potential of catechin derivatives as a potential myostatin inhibitor: A special view on Sarcopenic Obesity

Sarcopenic obesity has become a significant age-related metabolic problem. Catechins are flavanol, derivatives which poses a strong antioxidant activity. The major components of catechin derivatives. were identified through our physicochemical and pharmacokinetic parameters estimation. Therefore, in this study, network pharmacology was used to explore the multiple targets related to Sarcopenia, Metabolic syndrome, and obesity. The targets were identified from network analysis. The catechin derivatives were screened using Lipinski’s rule of five, Veber scale, Egan scale, and Muegge scale. From this drugglikness property catechin and Epicatechin was selected which were docked towards the myostatin inhibition PDB ID: 3HH2. Furthermore, the computational docking method on Catechin and Epicatechin with the stronger interaction towards myostatin inhibition receptor with the binding energy of −6.90 kcal/mol. and −7.0 kcal/mol from autodock software, respectively, for catechin and Epicatechin. Higher binding energy confirms the pharmacotherapeutic activity of Catechin and Epicatechin toward the myostatin inhibitor target.</p

Physicochemical investigation and molecular docking analysis of Maha yogaraj Guggulu tablet and virtual screening of its major bioactive compound

Guggulsterone plays a significant role in cholesterol-lowering by inhibiting Farnesoid X Receptor. The present study aims to identify the isomers of Guggulsterone with high binding affinity and good binding interaction with targeted protein and positive control atorvastatin. The pharmacokinetic parameters of Guggulsterone isomers were estimated from P.K.C.S.M. online server, and molecular docking analysis was performed from Autodock V.® 4.2.6 Program. From the computer-aided drug designing, we have confirmed that guggulsterone isomers are inhibitors of the CYP3A4 enzyme and hepatotoxic. Guggulsterone isomer showed a stronger binding affinity when compared with atorvastatin. The docking score for Guggulsterone was −9.28 kcal/mol, E-Guggulsterone −9.56 kcal/mol, Z-Guggulsterone −9.79 kcal/mol, M-Guggulsterone −9.45 kcal/mol, and positive control atorvastatin −8.26 kcal/mol. The present study revealed that the isomers of Guggulsterone have high binding affinity and good binding interaction with targeted proteins.</p

HCIP: An Online database for prediction CYP450 Enzyme Inhibition potential of bioactive compounds

Background: Concomitant administration of herbal medicine and conventional may lead to severe metabolism-oriented herb-drug interactions. However, detecting herb-drug interaction is expensive and higher time-consuming. Several computer-aided techniques have been proposed in recent years to predict drug interactions. However, most of the methods cannot predict herb-drug interactions effectively. Methods: Canonical SMILES of bioactive compounds was gathered from the PubChem online database, and its inhibition details were gathered PKCSM from the webserver. Results: By searching the bioactive compound name in the search bar of “The Herb-CYP450 Enzyme Inhibition Predictor online database” (HCIP- http://hcip.in/), it will provide the liver enzyme inhibition profile of the selected bioactive compound. For example; Guggulsterone:&nbsp; CYP3A4 inhibitor.&nbsp; Conclusion: The Herb-CYP450 Enzyme Inhibition Predictor online database is very peculiar and easy to determine the inhibition profile of the targeted bioactive compound. Keywords: CYP450; Enzyme inhibition; Bioactive Compounds; Online database; Herb-Drug Interactio

Novel Essential Oils Blend as a Repellent and Toxic Agent against Disease-Transmitting Mosquitoes

Bio-insecticidal research has focused on long-term vector control using essential oils (EOs). This study examined the larvicidal, oviposition-deterrent, and repellent properties of five medicinal herb-based EO formulations (EOFs) on mosquitoes that are vectors of dengue, filariasis, and malaria. EOFs were significantly more toxic to the larvae and pupae of Culex quinquefasciatus, Anopheles stephensi, and Aedes aegypti with LC50 = 9.23, 12.85, and 14.46 ppm, as well with 10.22, 11.39, and 12.81 ppm, with oviposition active indexes of −0.84, −0.95, and −0.92, respectively. Oviposition-deterrent repellence was found in 91.39%, 94.83%, and 96.09%. EOs and N, N-Diethyl-3-methylbenzamide (DEET) were prepared at various concentrations for time duration repellent bioassays (6.25–100 ppm). Ae. aegypti, An. stephensi, and Cx. quinquefasciatus were monitored for 300, 270, and 180 min, respectively. At 100 ppm, EOs and DEET had comparable repellence in terms of test durations. EOF’s primary components d-limonene (12.9%), 2,6-octadienal, 3,7-dimethyl, (Z) (12.2%), acetic acid, phenylmethyl ester (19.6%), verbenol (7.6%), and benzyl benzoate (17.4%) may be combined to make a mosquito larvicidal and repellant equivalent to synthetic repellent lotions. In the molecular dynamics simulations, limonene (−6.1 kcal/mol) and benzyl benzoate (−7.5 kcal/mol) had a positive chemical association with DEET (−6.3 kcal/mol) and interacted with the OBP binding pocket with high affinity and stability. This research will help local herbal product manufacturers and the cosmetics industry in developing 100% herbal insect repellent products to combat mosquito-borne diseases, including dengue, malaria, and filariasis