Synthesize palladium nanoparticles from the macroalgae Sargassum fusiforme: An eco-friendly tool in the fight against Plasmodium falciparum?

Although numerous drugs are practiced to control malaria and its vectors, more recently, eco-friendly control tools have been proposed to battle its etiologic agents. Thus, using green bionanotechnology approaches, we aimed to synthesize palladium nanoparticles (Pd NPs) from the macroalgae Sargassum fusiforme (Sf), its potential antiparasitic activity against P. falciparum, as well as its possible cytotoxicity, in HeLa cells. After the biosynthesis of the PdSf NPs, their characterization was carried out by UV-Vis, FESEM, and EDX analyses, and their hydrodynamic size, zeta potential, and surface area were determined. Furthermore, the functional groups of the PdSf NPs were analyzed by FT-IR and GC-MS. While PdSf NPs had an IC50 of 7.68 µg/mL (Chloroquine (CQ)-s) and 16.42 µg/mL, S. fusiforme extract had an IC50 of 14.38 µg/mL (CQ-s) and 35.27 µg/mL (CQ-r). With an IC50 value of 94.49 µg/mL, PdSf NPs exhibited the least toxic effect on the HeLa cells. The Lipinski rule of five and ADMET prediction were used to assess the in silico models of caffeine acid hexoside and quercetin 7-O-hexoside for the presence of drug-like properties. Pathogenic proteins, primarily responsible for motility, binding, and disease-causing, were the target of the structurally based docking studies between plant-derived compounds and pathogenic proteins. Thus, our study pioneered promising results that support the potential antiplasmodial activity of eco-friendly synthesized PdSf NPs using S. fusiforme extract against P. falciparum, opening perspectives for further exploration into the use of these NPs in malaria therapy.

Isolation and In silico Study of Curcumin from Curcuma longa and Its Anti-Diabetic Activity.

Natural products have been widely used for the management of various diseases that affect human health. Natural products are chemical substances that can be extracted with solvents and isolated by column chromatography techniques from the plant source. The development of new drugs from natural products is still challenging, and the most extensively studied plant material is turmeric, Curcuma longa, which is the chief source of curcumin. Curcumin is a bright yellow solid. In our present study, we have taken Curcuma longa, which is defatted with hexane, followed by being extracted with methanol as a solvent. The turmeric methanolic extract is taken for the isolation of curcumin. This was carried out and confirmed by spectroscopy techniques including 1H NMR, 13C NMR, ESI-HRMS, and FT-IR. The compound in silico ADME properties estimate falls within an acceptable range, and a molecular docking analysis shows that it has a higher binding affinity than reference standards. Based on the findings, it can be said that curcumin, a natural substance, has good therapeutic qualities when it is isolated.

CYP3A4 mediated pharmacokinetics drug interaction potential of Maha-Yogaraj Gugglu and E, Z guggulsterone.

Maha yogaraja guggulu (MYG) is a classical herbomineral polyherbal formulation being widely used since centuries. The aim of this study was to investigate the effect of MYG formulation and its major constituents E & Z guggulsterone on CYP3A4 mediated metabolism. In vitro inhibition of MYG and Guggulsterone isomers on CYP3A4 was evaluated by high throughput fluorometric assay. Eighteen Adult male Sprague-Dawley rats (200 ± 25 g body weight) were randomly divided into three groups. Group A, Group B and Group C were treated with placebo, MYG and Standard E & Z guggulsterone for 14 days respectively by oral route. On 15th day, midazolam (5 mg/kg) was administered orally to all rats in each group. Blood samples (0.3 mL) were collected from the retro orbital vein at 0.25, 0.5, 0.75, 1, 2, 4, 6, 12 and 24 h of each rat were collected. The findings from the in vitro & in vivo study proposed that the MYG tablets and its guggulsterone isomers have drug interaction potential when consumed along with conventional drugs which are CYP3A4 substrates. In vivo pharmacokinetic drug interaction study of midazolam pointed out that the MYG tablets and guggulsterone isomers showed an inhibitory activity towards CYP3A4 which may have leads to clinically significant interactions.

A Short Exploration of Selected Sensitive CYP3A4 Substrates (Probe Drug).

BACKGROUND: CYP450 enzymes in the liver have a significant role in the metabolism of xenobiotics. Probe drug strategy is broadly used to evaluate the pharmacodynamic and pharmacokinetic drug/ herb-drug interactions/ food-drug interactions. Probe drugs reveal the exact pathway of drug metabolism in the liver by their targeted tractability property. The CYP3A4 isoenzyme metabolizes the majority of the drugs (65%). METHODS: The characteristics of targeted probe drugs were observed from the admetSAR (version2) online database. RESULTS: Midazolam is widely used as a probe drug because of its peculiar character. Midazolam affirms the accurate and consistent prediction of pharmacokinetic mediated drug interactions even in nanogram concentrations with or without a potent CYP3A inhibitor. Remarkably, midazolam is used as a CYP3A4 substrate in the majority of in vivo studies. CONCLUSION: It is concluded that midazolam shows a good response in all clinical studies because of its lesser half-life and bioavailability when compared with other probe drugs.

Assessment of Herb-drug Interactions Based on the Pharmacokinetic Changes of Probe Drug, Midazolam.

BACKGROUND: In healthy volunteers, the probe drug method is widely practised to assess the pharmacokinetic mediated herb-drug interactions (HDI). We analyzed the clinical evidence of CYP3 A4 probe drug, Midazolam. METHODS: Literatures, where Midazolam was used as a probe drug for prediction of herb-drug interaction, were surveyed through an online database such as google scholar, Scopus, Cochrane, PubMed and clinicaltrials.gov. RESULTS: Midazolam was considered a sensitive probe for CYP3A4 substrates due to its bioavailability. We observed that not all the herbs are causing drug interaction. However, significant changes of the Midazolam pharmacokinetics were found after high-dose and long-term intake of some herbs and food supplements, suggesting the induction and/or inhibition of CYP activities. CONCLUSION: Probe drug technique is one of the easiest ways for predicting CYP enzyme-mediated herb-drug interactions. Midazolam shows a good response in clinical studies because of short halflife and low harmfulness compared with other probe drugs.