Dose-dependent Efficacy Research Articles

Enhanced brain delivery and antiproliferative activity of resveratrol using milk-derived exosomes

The polyphenol resveratrol (RSV) undergoes extensive phase II metabolism, which limits its bioavailability and bioactivity, including anticancer effects. Growing preclinical evidence reinforces milk-derived exosomes (EXOs) as promising nanocarrier drugs and bioactives delivery systems. Herein, to overcome the mentioned RSV’s drawbacks, EXOs were loaded with RSV (EXO-RSV) to evaluate its brain delivery in Sprague-Dawley rats and its in vitro antiproliferative effects against human neuroblastoma SH-SY5Y and glioblastoma U-87MG cancer cells compared with non-encapsulated RSV. Pharmacokinetic analyses in perfused brains showed RSV detection only after EXO-RSV administration, not after non-encapsulated RSV administration. Encapsulation also resulted in lower concentrations of phase II-derived RSV metabolites in circulation. Additionally, blood-brain barrier (BBB) transport assays using human brain microvascular endothelial cells (HBMECs) corroborated that encapsulation enhanced RSV transport efficiency and protected it from cellular metabolism. In vitro and in silico analyses of phase-II conjugates, primarily RSV 3-glucuronide, showed lower capacity than RSV to cross the BBB. Finally, EXO-RSV (47−750 nM) showed an increased dose-dependent antiproliferative efficacy on both cancer cell lines compared with the non-encapsulated RSV (10 μM), which was ineffective after 72 h of treatment. Our findings suggest that EXOs protect RSV from phase II metabolism and enhance its brain delivery and antiproliferative activity.

Effect of Zinc on improving silver diamine fluoride-derived tooth discoloration in vitro.

Silver Diamine Fluoride (SDF) is effective for arresting dental caries, presenting a valuable non-invasive treatment option in dentistry. Despite its therapeutic advantages, a significant drawback is the tooth discoloration that follows its application, which can affect patient acceptance. Addressing this aesthetic concern without diminishing the treatment's efficacy remains challenging in dental practice. This study explores strategies to improve the aesthetic outcomes of SDF treatments. This in vitro study assessed the efficacy of Zinc in reducing SDF-induced discoloration on dentin blocks and examined its impact on the physical properties of dentin, including hardness and roughness. Dentin blocks were pre-treated with various concentrations of Zinc, followed by SDF application. Color changes were analyzed using Image J software, and cytotoxicity was evaluated using the CytoTox-ONE™ Homogeneous Membrane Integrity Assay. Dentin surface characteristics, including micro-hardness and roughness, were assessed using scanning electron microscopy. The study results revealed a dose-dependent efficacy of Zinc in reducing discoloration caused by SDF on dentin, with higher Zinc concentrations showing better improvement in color outcomes. The application of a 20M Zinc solution prior to SDF treatment significantly reduced discoloration compared to SDF alone, measured on day 14. Additionally, no significant changes in the hardness or roughness of etched dentin were observed in Zinc + SDF group compared to the SDF alone group. Zinc treatments demonstrated a desirable outcome on mucosal cytotoxicity, comparable to that of the negative control. Zinc significantly reduced SDF-induced tooth discoloration in a dose-dependent manner without affecting the etched dentin's micro-hardness and roughness, potentially improving patient acceptance, especially in visible areas of the mouth. Further research is warranted to validate the effectiveness of this zinc-enhanced treatment protocol in vivo. Zinc-enhanced SDF treatments could enhance patient acceptance, especially in visible areas of the mouth, offering an improved option for caries management.

Paclitaxel and myricetin encapsulated hemoglobin nanoparticles: characterization and application

Hb is used as a carrier protein to encapsulate hydrophobic drugs PTX and MYN and has applications in cancer treatment. PTX and MYN encapsulated Hb NPs are synthesized by the acid denature method and are characterized by spectroscopic and electron microscopic techniques. The binding constant calculated for Hb and PTX is 3.83 x 108 M-1, which is the highest in the pH range tested for both drugs. The CD spectra also demonstrated maximum denaturation of Hb at pH 5.0 evidencing the opening of the Hb hydrophobic core. The acidic condition at pH 5.0 is optimized for the synthesis of drug- encapsulated NPs. FTIR spectra of Hb PTX NPs recorded higher shifts in the OH/carboxyl peak compared to Hb-MYN. SEM images of Hb-PTX NPs highlight the tetrahedral structure of the NPs and the round shape of Hb-MYN NPs. The size of Hb-MYN and Hb-PTX is around 38.0 and 44.0 nm respectively as measured by DLS. PTX-Hb NPs demonstrated higher dose-dependent apoptosis-inducing efficacy than MYN-Hb in the K562 cells.

Structure-based design and synthesis of novel FXIa inhibitors targeting the S2' subsite for enhanced antithrombotic efficacy.

Factor XIa (FXIa), a key component of the intrinsic coagulation pathway, has recently been recognized as a safe and effective target for antithrombotic therapy. Research indicates that FXIa inhibitors can lower bleeding risk compared to novel oral anticoagulants. In this study, we designed and synthesized a series of novel FXIa inhibitors based on the structure of Asundexian, with a particular focus on optimizing the P2' region to enhance binding to the S2' subsite of FXIa. This strategy led to the discovery of compound F47, which demonstrated significantly greater FXIa inhibition (IC50 = 2.0nM) compared to Asundexian (IC50 = 5.0nM). F47 also showed excellent anticoagulant activity in the aPTT assay (EC2x = 0.4μM), with strong efficacy and minimal impact on the extrinsic coagulation pathway. Additionally, F47 exhibited inhibitory activity against plasma kallikrein (PKal), with selectivity comparable to that of Asundexian. The compound also displayed acceptable stability in human liver microsomal stability assays. Molecular modeling revealed that F47 binds tightly to the S1, S1', and S2' pockets of FXIa while maintaining key interactions; notably, its P2' moiety forms two additional π-π stacking interactions with the crucial amino acid TYR143. Further studies demonstrated that F47 exhibits dose-dependent antithrombotic efficacy in a rat FeCl3-induced thrombosis model. Ongoing research aims to further elucidate the potential of compound F47 as a promising lead in antithrombotic therapy.

First-choice hormonal therapies for children with infantile epileptic spasms syndrome in South Asia: A network meta-analysis of randomized controlled trials.

Considering the peculiar challenges with infantile epileptic spasms syndrome (IESS) in South Asia and a wide variation in the usage of hormonal therapies, we compared the efficacy and safety of various hormonal therapies for children with IESS in South Asia. We searched PubMed, Embase, Scopus, and Web of Science databases from the inception until April 2024. We included only randomized clinical trials (RCTs) evaluating the efficacy and safety of hormonal therapies for IESS in the South Asian region. Complete cessation of epileptic spasms (ES), electro-clinical response, and time taken to be spasm-free at 2 or 6 weeks of therapy were efficacy outcomes, while the occurrence of adverse events was the safety outcome. Effect estimates were reported as odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CI) and Cochrane risk of bias 2.0 (ROB 2.0) used for quality assessment of each study. The surface under the cumulative ranking curve (SUCRA) was used to rank the different therapies and reported as a p-score ranging from 0 to 1. Of 747 citations, nine RCTs comprising 566 children with IESS were included. After 2-week treatment, dexamethasone (OR: 6.72; 95% CI: 1.47, 30.72), adrenocorticotropic hormone therapy (ACTH) high dose (HD) (OR: 5.30; 95% CI: 1.05, 26.91), and prednisolone HD (OR: 2.41; 95% CI:1.07, 5.46) had shown significantly greater efficacy for cessation of EScompared with ACTH low dose (LD). Similarly, for electroclinical response, dexamethasone (OR: 9.63; 95% CI: 1.99, 46.70) and prednisolone HD (OR: 3.46; 95% CI: 1.38, 8.68) had greater efficacy compared with ACTH LD. Safety outcomes revealed that hypertension was significantly less common with ACTH LD and prednisolone HD as compared with ACTH HD. This study provides quality evidence on preferred first-choice hormonal therapy for managing IESS in South Asia. ACTH HD, dexamethasone, and prednisolone HD are the most effective hormonal therapy options with dose-dependent therapeutic efficacy. PLAIN LANGUAGE SUMMARY: This study provides insights into the selection of first-line hormonal therapies among the various treatments for managing infantile epileptic spasms syndrome (IESS) in South Asia. The study findings suggested that the effectiveness of these therapies is dose-dependent, with high doses of ACTH, dexamethasone, and prednisolone being the most effective for achieving cessation of epileptic spasms.

Targeting protein homeostasis with small molecules as a strategy for the development of pan-coronavirus antiviral therapies

The COVID-19 pandemic has created a global health crisis, with challenges arising from the ongoing evolution of the SARS-CoV-2 virus, the emergence of new strains, and the long-term effects of COVID-19. Aiming to overcome the development of viral resistance, our study here focused on developing broad-spectrum pan-coronavirus antiviral therapies by targeting host protein quality control mechanisms essential for viral replication. Screening an in-house compound library led to the discovery of three candidate compounds targeting cellular proteostasis. The three compounds are (1) the nucleotide analog cordycepin, (2) a benzothiozole analog, and (3) an acyldepsipeptide analog initially developed as part of a campaign to target the mitochondrial ClpP protease. These compounds demonstrated dose-dependent efficacy against multiple coronaviruses, including SARS-CoV-2, effectively inhibiting viral replication in vitro as well as in lung organoids. Notably, the compounds also showed efficacy against SARS-CoV-2 delta and omicron strains. As part of this work, we developed a BSL2-level cell-integrated SARS-CoV-2 replicon, which could serve as a valuable tool for high-throughput screening and studying intracellular viral replication. Our study should aid in the advancement of antiviral drug development efforts.

Oral oxaborole MRX-5 exhibits efficacy against pulmonary Mycobacterium abscessus in mouse.

Mycobacterium abscessus (Mab) is an opportunistic pathogen common in patients with lung comorbidities and immunosuppression. There are no FDA-approved treatments, and current treatment has a failure rate exceeding 50%. The intravenous oxaborole MRX-6038 is active against Mab. This study evaluated MRX-5, the oral prodrug, against five Mab isolates in a mouse lung infection model. MRX-5 showed dose-dependent efficacy, with 15 and 45 mg/kg doses comparable to the standard of care, supporting progression to clinical trial.

33 - EG110A, a novel non-replicative HSV1-derived vector expressing the light chain of botulinum toxin F, shows dose-dependent efficacy in an acute intravesical capsaicin rat model

33 - EG110A, a novel non-replicative HSV1-derived vector expressing the light chain of botulinum toxin F, shows dose-dependent efficacy in an acute intravesical capsaicin rat model

The anticoagulant effects of milvexian, a novel small molecule factor XIa inhibitor, are neutralized by activated prothrombin complex concentrates and recombinant factor VIIa in human plasma and whole blood in vitro

BackgroundThe development of anticoagulants that provide antithrombotic efficacy without a concomitant bleeding risk remains an unmet clinical need in thrombosis. Although direct oral anticoagulants (DOACs) have a reduced incidence of major bleeding compared with warfarin, they still carry a bleeding risk, resulting in a suboptimal therapeutic index. Epidemiologic data suggest that inhibiting activated factor (F)XI may offer an improved safety profile with respect to bleeding risk compared with current-generation DOACs. Additionally, a phase II trial of milvexian in patients undergoing elective total knee replacement demonstrated robust dose-dependent efficacy with no statistically significant increase in bleeding. Nevertheless, the ability to rapidly and effectively correct FXIa inhibitor–induced anticoagulation may still be important in situations where patients experience uncontrolled bleeding or require emergency surgery. ObjectivesWe assessed the ability to normalize the anticoagulant effects of the novel small molecule FXIa inhibitor milvexian (BMS-986177/JNJ-70033093) in vitro using commercially available prohemostatic agents. MethodsMilvexian-associated anticoagulation and correction was evaluated in activated partial thromboplastin time clotting assays, thromboelastography, and kaolin-initiated thrombin generation assays. ResultsActivated prothrombin complex concentrates (PCCs) and recombinant factor (rF)VIIa corrected the anticoagulant effects of milvexian in activated partial thromboplastin time clotting assays, thromboelastography, and kaolin-initiated thrombin generation assays. In contrast, other agents including PCCs, rFIX, and rFVIII demonstrated either modest or no correction of milvexian-associated anticoagulation. ConclusionThis study demonstrated that currently available activated PCCs and rFVIIa normalize anticoagulation induced by milvexian in vitro. The clinical utility of these agents remains to be established.

Design of a potent and selective dual JAK1/TYK2 inhibitor

Janus kinase (JAK) inhibitors have gathered interest as treatments for several inflammatory and autoimmune diseases. The four first marketed inhibitors target JAK1, with varying selectivity towards other JAK family members, but none inhibit tyrosine kinase-2 (TYK2) at clinically relevant doses. TYK2 is required for the signaling of the interleukin (IL)-12 and IL-23 cytokines, which are key to the polarization of TH1 and TH17 cells, respectively; two cell subtypes that play major roles in inflammatory diseases. Herein, we report our effort towards the optimization of a potent and selective dual JAK1/TYK2 inhibitor series starting from a HTS hit. Structural information revealed vectors required to improve both JAK1 and TYK2 potency as well as selectivity towards JAK2. The potent inhibition of both JAK1 (3.5 nM) and TYK2 (5.7 nM) in biochemical assays by our optimized lead compound, as well as its notable selectivity against JAK2, were confirmed in cellular and whole blood assays. Inhibition of TYK2 by the lead compound was demonstrated by dose-dependent efficacy in an IL-23-induced psoriasis-like inflammation mouse model.

Design, Biological Characterization, and Discovery of Novel Cyclohexenyl Derivatives as Kinesin KIF18A Inhibitors for the Treatment of Ovarian Cancer.

A novel class of kinesin KIF18A inhibitors were discovered through modification of the clinical compound AMG650. Structure-activity relationship (SAR) study led to the discovery of compound 16 with an alkenyl motif, a highly potent KIF18A inhibitor, which displayed a favorable pharmacological profile and excellent efficacy in a mouse model of an OVCAR-3 xenograft tumor. Oral administration of 16 can induce a dose-dependent antitumor efficacy in the OVCAR-3 model without significant reduction in body weight. Compound 16 showed potential as a candidate for the clinical treatment of ovarian cancer.

Dynamic monitoring of a 3D-printed airway tissue model using an organic electrochemical transistor

Assessing the transepithelial resistance to ion flow in the presence of an electric field enables the evaluation of the integrity of the epithelial cell layer. In this study, we introduce an organic electrochemical transistor (OECT) interfaced with a 3D living tissue, designed to monitor the electrical resistance of cellular barriers in real-time. We have developed a non-invasive, tissue-sensing platform by integrating an inkjet-printed large-area OECT with a 3D-bioprinted multilayered airway tissue. This unique configuration enables the evaluation of epithelial barrier integrity through the dynamic response capabilities of the OECT. Our system effectively tracks the formation and integrity of 3D-printed airway tissues in both liquid-liquid and air-liquid interface culture environments. Furthermore, we successfully quantified the degradation of barrier function due to influenza A (H1N1) viral infection and the dose-dependent efficacy of oseltamivir (Tamiflu®) in mitigating this degradation. The tissue-electronic platform offers a non-invasive and label-free method for real-time monitoring of 3D artificial tissue barriers, without disturbing the cellular biology. It holds the potential for further applications in monitoring the structures and functions of 3D tissues and organs, significantly contributing to the advancement of personalized medicine.

Novel biopolymer spray formulation for drug delivery in precision dentistry

Addressing the growing challenges of periodontal and peri-implant diseases, this study first reports a promising advancement in precision dentistry: an intricately formulated biopolymer spray designed for precise, localized drug delivery during tailored dental procedures. Poly (lactic-co-glycolic acid) (PLGA), recognized for its controlled release, biodegradability, and FDA-approved biocompatibility, forms the core of this formulation. Utilizing the double emulsion method, PLGA microparticles (PLGA-MPs) were loaded with dental antibiotics: sodium amoxicillin (AMX-Na), trihydrate amoxicillin (AMX-Tri), and metronidazole (Met). This antibiotic combination was thoughtfully selected to meet the distinctive requirements of the most impacting dental treatments. The newly developed biopolymer spray underwent thorough in-vitro analysis, revealing an optimized release curve for antibiotics over time, guaranteeing sustained therapeutic efficacy, and dose-dependent efficacy, accommodating personalized treatment approaches. The positive outcomes position the novel biopolymer spray formulation the leaders in advancing localized drug delivery during dental procedures. Moreover, the precise application and the tunable formulation meets the concept of precision medicine: in detail, this formulation represents a significant stride in dental therapeutics, significantly contributing to the predictability of dental implantology.

Assessment of Phytochemical Constituents, Antimicrobial Activity, Impurity and Heavy Metal Content of Gynura nepalensis

This study explores the multifaceted area of herbal medicine, focusing on Gynura nepalensis, a medicinal plant. The qualitative analyses confirmed the presence of alkaloids, glycosides, phenols, tannins, flavonoids, protein-amino acids, saponins, and carbohydrates. Terpenoids and resin were apparently missing. The antimicrobial activity of the plant extract was assessed and it revealed dose-dependent efficacy against microbial growth. Additionally, the study scrutinized the total ash content, suggesting a moderate level of impurity, and evaluated the heavy metal concentration, finding it well below acceptable limits. Overall, the findings establish the promising role of Gynura nepalensis in natural medicine, urging further investigations and potential applications in integrated healthcare. Bangladesh Pharmaceutical Journal 27(2): 193-200, 2024 (July)

Biocontrol Mechanisms of Three Plant Essential Oils Against Phytophthora infestans Causing Potato Late Blight.

Late blight, caused by the notorious pathogen Phytophthora infestans, poses a significant threat to potato (Solanum tuberosum) crops worldwide, impacting their quality as well as yield. Here, we aimed to investigate the potential use of cinnamaldehyde, carvacrol, and eugenol as control agents against P. infestans and to elucidate their underlying mechanisms of action. To determine the pathogen-inhibiting concentrations of these three plant essential oils (PEOs), a comprehensive evaluation of their effects using gradient dilution, mycelial growth rate, and spore germination methods was carried out. Cinnamaldehyde, carvacrol, and eugenol were capable of significantly inhibiting P. infestans by hindering its mycelial radial growth, zoospore release, and sporangium germination; the median effective inhibitory concentration of the three PEOs was 23.87, 8.66, and 89.65 μl/liter, respectively. Scanning electron microscopy revealed that PEOs caused the irreversible deformation of P. infestans, resulting in hyphal shrinkage, distortion, and breakage. Moreover, propidium iodide staining and extracellular conductivity measurements demonstrated that all three PEOs significantly impaired the integrity and permeability of the pathogen's cell membrane in a time- and dose-dependent manner. In vivo experiments confirmed the dose-dependent efficacy of PEOs in reducing the lesion diameter of potato late blight. Altogether, these findings provide valuable insight into the antifungal mechanisms of PEOs vis-à-vis late blight-causing P. infestans. By utilizing the inherent capabilities of these natural compounds, we could effectively limit the harmful impacts of late blight on potato crops, thereby enhancing agricultural practices and ensuring the resilience of global potato food production.

Metformin monotherapy versus predominantly older non-metformin antidiabetic medications for cerebrovascular risk in early type 2 diabetes management.

Choosing the initial treatment for type 2 diabetes (T2D) is pivotal, requiring consideration of solid clinical evidence and patient characteristics. Despite metformin's historical preference, its efficacy in preventing cerebrovascular events lacked empirical validation. This study aimed to evaluate the associations between first-line monotherapy (metformin or non-metformin antidiabetic medications) and cerebrovascular complications in patients with T2D without diabetic complications. We analysed 9090 patients with T2D without complications who were prescribed either metformin or non-metformin medications as initial therapy. Propensity score matching ensured group comparability. Cox regression analyses, stratified by initial metformin use, assessed cerebrovascular disease risk, adjusting for multiple covariates and using competing risk analysis. Metformin exposure was measured using cumulative defined daily doses. Metformin users had a significantly lower crude incidence of cerebrovascular diseases compared with non-users (p < .0001). Adjusted hazard ratios (aHRs) consistently showed an association between metformin use and a lower risk of overall cerebrovascular diseases (aHRs: 0.67-0.69) and severe events (aHRs: 0.67-0.69). The association with reduced risk of mild cerebrovascular diseases was significant across all models (aHRs: 0.73-0.74). Higher cumulative defined daily doses of metformin correlated with reduced cerebrovascular risk (incidence rate ratio: 0.62-0.94, p < .0001), indicating a dose-dependent effect. Metformin monotherapy is associated with a reduced risk of cerebrovascular diseases in early-stage T2D, highlighting its dose-dependent efficacy. However, the observed benefits might also be influenced by baseline differences and the increased risks associated with other medications, such as sulphonylureas. These findings emphasize the need for personalized diabetes management, particularly in mitigating cerebrovascular risk in early T2D stages.

Implications of silver nanoparticles for H. pylori infection: modulation of CagA function and signaling.

Helicobacter pylori infection poses a significant health burden worldwide, and its virulence factor CagA plays a pivotal role in its pathogenesis. In this study, the interaction between H. pylori-infected AGS cells and silver nanoparticles (AgNPs) was investigated, with a focus on the modulation of CagA-mediated responses, investigated by western blotting. Both, the dose-dependent efficacy against H. pylori (growth curves, CFU assay) and the impact of the nanoparticles on AGS cells (MTT assay) were elucidated. AGS cells infected with H. pylori displayed dramatic morphological changes, characterized by elongation and a migratory phenotype, attributed to CagA activity. Preincubation of H. pylori with AgNPs affected these morphological changes in a concentration-dependent manner, suggesting a correlation between AgNPs concentration and CagA function. Our study highlights the nuanced interplay between host-pathogen interactions and the therapeutic potential of AgNPs in combating H. pylori infection and offers valuable insights into the multifaceted dynamics of CagA mediated responses.

Evaluation of the impact of systemic dexamethasone dosage on docetaxel-induced hand-foot syndrome in patients with breast cancer

Hand-foot syndrome (HFS) is a frequently occurring and treatment-requiring adverse effect of docetaxel. We previously reported that systemic dexamethasone (DEX) prevents the other docetaxel-induced adverse inflammatory effects in a dose-dependent manner. This study aimed to evaluate the dose-dependent efficacy of systemic DEX in attenuating HFS in patients with breast cancer receiving docetaxel. Patients with breast cancer receiving docetaxel (75 mg/m2)-containing regimens (n = 111) were divided into 4 and 8 mg/day DEX groups, with each DEX dose administered on days 2–4, and analyzed retrospectively. Development of all-grade HFS in all treatment cycles was significantly lower in the 8 mg group (50.0%) than in the 4 mg group (73.0%, P = 0.03), with primary endpoint accomplishment. Moreover, its development in the first cycle was also lower in the 8 mg group than in the 4 mg group. These results were confirmed in a propensity score-matched population. Logistic regression analysis suggested higher DEX dosage as an independent preventive factor (adjusted odds ratio 0.35; 95% confidence interval 0.14–0.86, P = 0.02 for all cycles; 0.26, 0.11–0.63, P = 0.003 for the first cycle). Our study suggests that systemic DEX prevents the occurrence of docetaxel-induced HFS in patients with breast cancer in a dose-dependent manner in a real-world setting.

Efficacy and Safety of Oral Semaglutide in the Treatment of Type 2 Diabetes: A Meta-Analysis.

This study aims to systematically review the efficacy and safety of oral semaglutide in the treatment of type 2 diabetes mellitus (T2DM) and provide a basis for the rational use of the drug in clinical practice. From the database's inception until February 2023, a systematic search was conducted in PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and China Science and Technology Journal Database to identify randomized controlled trials (RCTs) comparing the efficacy of oral semaglutide at dosages of 3, 7, and 14 mg (trial group) against placebo or other positive control drugs (control group) for the treatment of T2DM. Following literature screening and data extraction, the bias risk assessment tool in the Cochrane reviewer handbook 5.1.0 was used to evaluate the literature quality. Meta-analysis was carried out with RevMan 5.4 software. A total of 10 RCTs with 9541 patients were included. The meta-analysis results revealed that compared with placebo or positive control drugs (empagliflozin, sitagliptin, liraglutide, and dulaglutide), oral semaglutide significantly reduced the hemoglobin A1c (HbA1c) in patients (compared to placebo, 3 mg [MD = -0.61%, 95% CI (-0.89, -0.34)], 7 mg [MD = -1.12%, 95% CI (-1.45, -0.79)], 14 mg [MD = -1.08%, 95% CI (-1.32, -0.85)]; compared to positive control drugs (7 mg [MD = -0.26%, 95% CI (-0.38, -0.15)], 14 mg [MD = -0.37%, 95% CI (-0.52, -0.23)]). Oral semaglutide also showed certain advantages over placebo or positive control drugs in terms of weight loss, HbA1c reduction achievement rate, fasting plasma glucose level, and body mass index with overall dose-dependent efficacy. The incidence of nausea, diarrhea, and vomiting caused by oral semaglutide was higher than that of the placebo or positive control drugs, and the incidence of appetite decrease or constipation was higher than that of the placebo. Severe or symptomatic hypoglycemic episodes were reduced compared to positive control drugs. Oral semaglutide has definite clinical benefits of reducing blood glucose, body weight, reducing the risk of hypoglycemia, and with good safety.

Assessment of &lt;i&gt;In vitro&lt;/i&gt; antioxidant and Analgesic activity of Ethyl acetate fraction of &lt;i&gt;Urena Lobata&lt;/i&gt; leaves

Background: The primary aim of this study is to identify the most active fraction from Urena lobata leaves and subsequently evaluate the analgesic and antioxidant accomplishments of the identified potent extract. The focus is on determining the fraction with the highest efficacy for potential therapeutic applications. Methods: U. lobata leaves were consecutively extracted with solvents like n-hexane, chloroform, ethyl acetate, and methanol. The concentrated fractions underwent initial phytochemical screening. The fraction exhibiting the highest activity, as determined by the carrageenan model, was further evaluated for its analgesic potential through the hot plate and acetic acid-induced writhing methods. In-vitro antioxidant activity was evaluated through DPPH and FRAP assays. Results: The preliminary phytochemical analysis of U. lobata leaf fractions exposed the presence of steroids, triterpenes, alkaloids, carbohydrates, tannins, and flavonoids. In the carrageenan-induced hind paw edema model, the ethyl acetate fraction of U. lobata leaf (ULEAF) demonstrated the highest anti-inflammatory effects, comparable to the standard drug Diclofenac sodium. Evaluation of analgesic potential using the hot-plate method and acetic acid-induced writhing test showed dose-dependent efficacy, with 500 mg/kg ULEAF exhibiting effects similar to ibuprofen. In vitro, antioxidant assays indicated potent radical scavenging and reducing power in the ethyl acetate fraction. Conclusion: In conclusion, U. lobata leaf fractions exhibited potent anti-inflammatory properties, with the ethyl acetate fraction demonstrating notable analgesic and antioxidant activity. These findings support the plant’s therapeutic potential for further exploration in pharmaceutical development.