An in vivo and in silico evaluation of the hepatoprotective potential of Gynura procumbens: A promising agent for combating hepatotoxicity.

INTRODUCTION: The liver, the most important metabolic organ of the body, performs a wide variety of vital functions. Hepatic cell injury occurs by the activation of reactive oxygen species (ROS) that are generated by carbon tetrachloride (CCl4), xenobiotics, and other toxic substances through cytochrome P450-dependent steps resulting from the covalent bond formation with lipoproteins and nucleic acids. Observing the urgent state of hepatotoxic patients worldwide, different medicinal plants and their properties can be explored to combat such free radical damage to the liver. In vivo and in silico studies were designed and conducted to evaluate the antioxidant and hepatoprotective properties of Gynura procumbens in rats. MATERIALS AND METHODS: Gynura procumbens leaves were collected and extracted using 70% ethanol. The required chemicals CCl4, standard drug (silymarin), and blood serum analysis kits were stocked. The in vivo tests were performed in 140 healthy Wister albino rats of either sex under well-controlled parameters divided into 14 groups, strictly maintaining Institutional Animal Ethics Committee (IEAC) protocols. For the histopathology study, 10% buffered neutral formalin was used for organ preservation. Later the specimens were studied under a fluorescence microscope. In silico molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies were performed, and the results were analyzed statistically. RESULTS AND DISCUSSION: Gynura procumbens partially negate the deleterious effect of carbon tetrachloride on normal weight gain in rats. The elevated level of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), creatinine, LDH, total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG), malondialdehyde (MDA), deoxyribonucleic acid (DNA) fragmentation ranges, gamma-glutamyl transferase (γ-GT) in CCl4 treated groups were decreased by both standard drug silymarin and G. procumbens leaf extract. We have found significant & highly significant changes statistically for different doses, here p<0.05 & p<0.01, respectively. On the other hand, G. procumbens and silymarin displayed Statistically significant (p<0.05) and high significant(p<0.01) increased levels of HDL, CAT SOD (here p<0.05 & p<0.01 for different doses) when the treatment groups were compared with the disease control group. Because the therapeutic activity imparted by plants and drugs accelerates the movement of the disturbed pathophysiological state toward the healthy state. In the molecular docking analysis, G. procumbens phytoconstituents performed poorly against transforming growth factor-beta 1 (TGF-ß1) compared to the control drug silymarin. In contrast, 26 phytoconstituents scored better than the control bezafibrate against peroxisome proliferator-activated receptor alpha (PPAR-α). The top scoring compounds for both macromolecules were observed to form stable complexes in the molecular dynamics simulations. Flavonoids and phenolic compounds performed better than other constituents in providing hepatoprotective activity. It can, thus, be inferred that the extract of G. procumbens showed good hepatoprotective properties in rats.

Aggregation kinetics and stability of biodegradable nanoplastics in aquatic environments: Effects of UV-weathering and proteins.

Plastic pollution caused by conventional plastics has promoted the development and use of biodegradable plastics. However, biodegradable plastics do not degrade readily in water; instead, they can generate micro- and nanoplastics. Compared to microplastics, nanoplastics are more likely to cause negative impacts to the aquatic environment due to their smaller size. The impacts of biodegradable nanoplastics highly depend on their aggregation behavior and colloidal stability, which still remain unknown. Here, we studied the aggregation kinetics of biodegradable nanoplastics made of polybutylene adipate co-terephthalate (PBAT) in NaCl and CaCl2 solutions as well as in natural waters before and after weathering. We further studied the effect of proteins on aggregation kinetics with both negative-charged bovine serum albumin (BSA) and positive-charged lysozyme (LSZ). For pristine PBAT nanoplastics (before weathering), Ca2＋ destabilized nanoplastic suspensions more aggressively than Na+, with the critical coagulation concentration being 20 mM in CaCl2 vs 325 mM in NaCl. Both BSA and LSZ promoted the aggregation of pristine PBAT nanoplastics, and LSZ showed a more pronounced effect. However, no aggregation was observed for weathered PBAT nanoplastics under most experimental conditions. Further stability tests demonstrated that pristine PBAT nanoplastics aggregated substantially in seawater, but not in freshwater, and only slightly in soil pore water; while weathered PBAT nanoplastics remained stable in all natural waters. These results suggest that biodegradable nanoplastics, especially weathered biodegradable nanoplastics, are highly stable in the aquatic environment, even in the marine environment.

Minimal Impacts of Microplastics on Soil Physical Properties under Environmentally Relevant Concentrations.

Agricultural soils are a major reservoir of microplastics, and concerns have arisen about the impacts of microplastics on soil properties and functioning. Here, we measured the physical properties of a silt loam in response to the incorporation of polyester fibers and polypropylene granules over a wide range of concentrations. We further elucidated the underlying mechanisms by determining the role of microplastic shape and the baseline effects from the amendment of soil particles. The incorporation of microplastics into soil tended to increase contact angle and saturated hydraulic conductivity and decrease bulk density and water holding capacity, but not affect aggregate stability. Polyester fibers affected soil physical properties more profoundly than polypropylene granules, due to the vastly different shape of fibers from that of soil particles. However, changes in soil properties were gradual, and significant changes did not occur until a high concentration of microplastics was reached (i.e., 0.5% w/w for polyester fibers and 2% w/w for polypropylene granules). Currently, microplastic concentrations in soils not heavily polluted with plastics are far below these concentrations, and results from this study suggest that microplastics at environmentally relevant concentrations have no significant effects on soil physical properties.

Assessing the Self-reported After Events Following Immunization of COVID-19 Vaccines in Turkey and Bangladesh.

Though mass vaccination programs helped to reduce the severity of the ongoing pandemic, various unwanted effects were reported in Turkey and Bangladesh after taking vaccines. The purpose of this study was to evaluate and compare the adverse effects of several vaccines in Turkey and Bangladesh and how the population of both countries prioritizes the continuation of vaccination compared to the side effects. An online survey with a pretest was conducted to gather data over the research period from July 10, 2021 to December 10, 2021. Finally, the questionnaire was shared with the mass population of Turkey and Bangladesh who have received at least one or two doses of the COVID-19 vaccines. The quality of the questionnaire was evaluated with Cronbach's alpha test. The study consisted of 1508 respondents from Bangladesh and 602 respondents from Turkey. Among the total 2110 respondents, 50.0% were male 66.8% were from the 18-30 years age range, and 77.5% reported living in the city area. Among all the respondents, 64.99% of those vaccinated in Bangladesh and 67.28% of those vaccinated in Turkey reported side effects after vaccinations. Participants receiving mRNA vaccines (Pfizer and Moderna) experienced the most side effects, with many reporting pain at the injection site in both nations. Following that, fever, body pain, and headache were common in Bangladesh, whereas body pain, fatigue, and arm numbness were common in Turkey. The study found no significant adverse events reported in Turkey and Bangladesh following the first and second doses of COVID-19 vaccination. These COVID-19 vaccines showed similar patterns of efficacy and safety during the short period of analysis. Vaccines from different manufacturers showed a non-significant level of adverse events during this binational AEFI approach to COVID-19 vaccines. More studies are recommended on the efficacy and safety of several vaccines to discover unexpected effects.

In Vivo and In Silico Assessment of Diabetes Ameliorating Potentiality and Safety Profile of Gynura procumbens Leaves.

BACKGROUND: Diabetes mellitus is one of the most notable health dilemmas. Analyzing plants for new antidiabetic remedies has become an impressive territory for life science researchers. Gynura procumbens has long been used to treat diabetes. Thus, we strived to ascertain the hypoglycemic potentiality of extract of leaves of G. procumbens by in vivo and in silico approaches. METHODS: Fresh leaves of G. procumbens were collected and shade-dried to prepare ethanolic extracts to evaluate pharmacological parameters. Diabetes was induced in rats via injecting alloxan through the intraperitoneal route at a dose of 150 mg/kg body weight. Humalyzer 3000 was used to perform a biochemical assay of collected samples from rats. Anti-hyperglycemic activity study along with overdose toxicity test was performed. The pharmacological activity of this plant was also evaluated through a molecular docking study. This in silico study investigated the binding affinity of natural ligands from G. procumbens against glycoside hydrolase enzymes. RESULTS: We detected a peak plasma concentration of G. procumbens at 3 hours 45 minutes that is roughly similar to the peak plasma concentration of metformin. Again, in OGTT and anti-hyperglycemic tests, it has been ascertained that both plant extract and metformin can exert significant (P < 0.05) and highly significant (P < 0.01) hypoglycemic activity in a dose-dependent manner. Metformin exhibited better therapeutic efficacy than that of plant extract, but it possessed null statistical significance. Also, our safety profile expressed that, similar to metformin, the plant extract can restore the disturbed pathological state in a dose-oriented approach with a wide safety margin. In silico study also validated the potentialities of natural constituents of G. procumbens. Conclusion. This study suggested that G. procumbens can be considered as potential antidiabetic plant. Robust and meticulous investigation regarding plant chemistry and pharmacology in the future may bring about a new dimension that will aid in discovering antidiabetic drugs from this plant in the diabetes management system.

An evaluation of pharmacological healing potentialities of Terminalia Arjuna against several ailments on experimental rat models with an in-silico approach.

Herbal remedies have been used in many cultures for decades to treat illnesses. These medicinal plants have been found to contain various phytochemical compounds that can help to cure mild to severe illnesses. The inadequacies of conventional medicines and their unusual side effects sparked a determined search for alternative natural therapeutic agents. Another reason for this hunt could be the availability and fewer side effects of natural products. T. arjuna is widely used in traditional medicine to alleviate various diseases like relieving pain, ameliorating diabetes, mitigating inflammation, and back-pedaling of depression. In this study, the ethanolic extract of T. arjuna possesses a promising effect on the animal model (p < 0.05/p < 0.01) as an antihyperglycemic, analgesic, anti-inflammatory, and antidepressant agent, but in a dose-dependent manner. The lower dose of T. arjuna was found to be capable of reversing the disturbed physiological state at a significant level (p < 0.05). However, a higher dose of T. arjuna exerts better therapeutic effects for those diseases. This animal study aims to evaluate the anti-diabetic, anti-depressant, and anti-inflammatory properties of T. arjuna compared to conventional marketed drugs. We will perform an in-silico study for active constituents of T. arjuna against their proposed targets and look for the molecular cascade on their claimed pharmacological properties. This study shows that different doses of T. arjuna bark extracts give similar therapeutic responses compared with established marketed drugs in managing hyperglycemia, stress-induced depression, and inflammation. Besides, our docking study reveals that flavonoids and triterpenoid active constituents of T. arjuna play an important role in its usefulness. This study, therefore, scientifically confirmed the traditional use of this medicinal plant in the management of several diseased conditions.

Current Knowledge Regarding Pharmacological Profile and Chemical Constituents of Gynura procumbens.

Gynura procumbens (Lour.) Merr. is a well-known plant used in folkloric medicine in tropical Asian countries. The plant is prevalently employed by traditional healers in the treatment of diabetes, cancer, hypertension, inflammation, fever, and skin disorders. Several scientific studies reported that Gynura procumbens possesses considerable therapeutic value for the development of emerging treatment options. The diverse pharmacological effects of this plant are attributed to its vast phytoconstituent content. Different chemical classes, including alkaloids, flavonoids, phenolics, steroids, proteins, and polysaccharides, have been isolated from this plant. In this review, we tried to explore the different aspects of Gynura procumbens as an established medicinal plant. The data gathered here give an indication that the plant Gynura procumbens is a good natural source of chemical compounds with different types of pharmacological actions, and these chemical compounds can be used as models for the development of de novo therapeutic agents.

A Retrospective Cross-Sectional Study Assessing Self-Reported Adverse Events following Immunization (AEFI) of the COVID-19 Vaccine in Bangladesh.

BACKGROUND: The Oxford-AstraZeneca vaccine (Covishield) was the first to be introduced in Bangladesh to fight the ongoing global COVID-19 pandemic. As this vaccine had shown some side-effects in its clinical trial, we aimed to conduct a study assessing short-term adverse events following immunization (AEFIs) in Bangladesh. METHOD: A cross-sectional study was conducted on social and electronic media platforms by delivering an online questionnaire among people who had taken at least one dose of the COVID-19 vaccine. The collected data were then analysed to evaluate various parameters related to the AEFIs of the respondents. RESULTS: A total of 626 responses were collected. Of these, 623 were selected based on complete answers and used for the analysis. Most of the respondents were between 30-60 years of age, and 40.4% were female. We found that a total of 8.5% of the total respondents had been infected with the SARS-CoV-2 virus. Our survey revealed that out of 623 volunteers, 317 reported various side-effects after taking the vaccine, which is about 50.88% of the total participants. The majority of participants (37.07%, 231/623) reported swelling and pain at the injection site and fever (25.84%, 162/623); these were some of the common localized and generalized symptoms after the COVID-19 vaccine administration. CONCLUSION: The side-effects reported after receiving the Oxford-AstraZeneca vaccine (Covishield) are similar to those reported in clinical trials, demonstrating that the vaccines have a safe therapeutic window. Moreover, further research is needed to determine the efficacy of existing vaccines in preventing SARS-CoV-2 infections or after-infection hospitalization.

Effects of Surfactants on Itraconazole-HPMCAS Solid Dispersion Prepared by Hot-Melt Extrusion I: Miscibility and Drug Release.

Hydroxypropyl methylcellulose acetate succinate (HPMCAS) has been widely investigated as a carrier for amorphous solid dispersion (ASD) of poorly water-soluble drugs. However, its use has mostly been limited to ASDs prepared by spray drying using organic solvents, and the solvent-free method, hot-melt extrusion (HME), has only limited use because it requires high processing temperature where the polymer and drug may degrade. In this investigation, surfactants were used as plasticizers to reduce the processing temperature. Their effects on drug release were also determined. To determine suitability of using surfactants, the miscibility of HPMCAS with 3 surfactants (poloxamer 188, poloxamer 407, and d-alpha tocopheryl polyethylene glycol 1000 succinate) and a model drug, itraconazole (ITZ), was studied by film casting. HPMCAS was miscible with ITZ (>30%) and each surfactant (>20%), and in ternary HPMCAS-ITZ-surfactant (60:20:20) system. ASDs prepared by HME of HPMCAS-ITZ-surfactant mixtures (70:20:10 and 65:20:15) at 160°C were physically stable after exposure to 40°C and 75% relative humidity for 1 month. The presence of 15% w/w surfactant provided up to 50% drug release at pH 1 as compared to only 8% from ASDs with HPMCAS alone. On changing the pH of the dissolution medium from 1 to 6.8 in a step-dissolution process, complete drug release (90%-100%) and extremely high apparent supersaturation (∼75,000 times) of ITZ were observed when the solutions were filtered through 0.45 µm filters. The apparently supersaturated solutions consisted of colloidal particles of ∼300 nm size. The present study demonstrates that stable ASDs with improved processability and drug release may be prepared by HME.

Formulation of 3D Printed Tablet for Rapid Drug Release by Fused Deposition Modeling: Screening Polymers for Drug Release, Drug-Polymer Miscibility and Printability.

The primary aim of this study was to identify pharmaceutically acceptable amorphous polymers for producing 3D printed tablets of a model drug, haloperidol, for rapid release by fused deposition modeling. Filaments for 3D printing were prepared by hot melt extrusion at 150°C with 10% and 20% w/w of haloperidol using Kollidon® VA64, Kollicoat® IR, Affinsiol™15 cP, and HPMCAS either individually or as binary blends (Kollidon® VA64 + Affinisol™ 15 cP, 1:1; Kollidon® VA64 + HPMCAS, 1:1). Dissolution of crushed extrudates was studied at pH 2 and 6.8, and formulations demonstrating rapid dissolution rates were then analyzed for drug-polymer, polymer-polymer and drug-polymer-polymer miscibility by film casting. Polymer-polymer (1:1) and drug-polymer-polymer (1:5:5 and 2:5:5) mixtures were found to be miscible. Tablets with 100% and 60% infill were printed using MakerBot printer at 210°C, and dissolution tests of tablets were conducted at pH 2 and 6.8. Extruded filaments of Kollidon® VA64-Affinisol™ 15 cP mixtures were flexible and had optimum mechanical strength for 3D printing. Tablets containing 10% drug with 60% and 100% infill showed complete drug release at pH 2 in 45 and 120 min, respectively. Relatively high dissolution rates were also observed at pH 6.8. The 1:1-mixture of Kollidon® VA64 and Affinisol™15 cP was thus identified as a suitable polymer system for 3D printing and rapid drug release.