A comprehensive account on ethnobotany, phytochemistry and pharmacological insights of genus Celtis.

The plants of Celtis L. genus have been traditionally used to cure aches, sore throats, fevers, cancer, sexually transmitted diseases, sexual weakness, diarrhea, stomach problems, amenorrhea, menstrual disorders, kidney stones, and pain. The review aims to give a comprehensive account of the current state of ethnopharmacology, phytochemistry, and biological activities of the Celtis genus, as well as to describe the potential area of future avenues. Information on the Celtis genus was obtained from internet sources such as Google Scholar, Web of Science, PubMed, ScienceDirect, and so on by using appropriate keywords, including ethnobotanical, pharmacological, pharmaceutical, bioactivity, phytochemistry, and botanical features of the Celtis genus. This review identified 14 species in the genus Celtis that have a phytopharmacological investigation, including C.africana Burm. f., C. australis L., C. occidentalis L., C. sinensis Pers., C. philippensis Blanco., C. tetrandra Roxb., C. tessmannii Rendle., C. jessoensis Koidz., C. adolfi-friderici Engl., C. iguanaea (Jacq.) Sarg., C. laevigata Wild., C. pallida Torr., C. zenkeri Engl., and C. tournefortii Lam. This genus contains many classified phytoconstituents, such as terpenoids, organic acids, flavonoids, and volatile compounds. Their extracts and pure substances have been shown to have the same anticancer, antibacterial, anti-inflammatory, antioxidant, hepatoprotective, cardioprotective, urease-inhibiting, and antidiarrheal properties as their traditional uses. In terms of current information on ethnopharmacology, phytochemicals, and pharmacological uses, the data acquired in this review could be beneficial and needed for future research. Some phytoconstituents (for instance, kaempferol, myricetin, quercetin, and eugenol) and extracts (for example, leaves, seeds, and ripe fruits extracts of C. australis) showed tremendous results in preliminary testing with promising antimicrobial, anticancer, and urease inhibitory effects. Further research and clinical investigations are needed to develop them as lead compounds and neutraceuticals, which may provide an advance over traditional medicinal systems.

Uncovering Novel Protein Partners of Inducible Nitric Oxide Synthase in Human Testis.

Peroxidative damage to human spermatozoa has been shown to be the primary cause of male infertility. The possible role of nitric oxide (NO) in affecting sperm motility, capacitation, and acrosome reaction has been reported, too. The overproduction of NO by the enzyme inducible nitric oxide synthase (iNOS) could be responsible as it has been implicated in the pathogenesis of many diseases. There have been many studies on regulating iNOS function in various tissues, especially by protein-protein interaction; however, no study has looked for iNOS-interacting proteins in the human testis. Here, we have reported the identification of two proteins that interact with iNOS. We initially undertook a popular yeast two-hybrid assay to screen a human testis cDNA library in yeast using an iNOS-peptide fragment (amino acids 181-335) as bait. We verified our data using the mammalian chemiluminescent co-IP method; first, employing the same peptide and, then, a full-length protein co-expressed in HEK293 cells in addition to the candidate protein. In both cases, these two protein partners of iNOS were revealed: (a) sperm acrosome-associated 7 protein and (b) retinoblastoma tumor-suppressor binding protein.

Isolation and immunosuppressive functions of myeloid-derived suppressor cell-derived exosomes.

Myeloid-derived suppressor cells (MDSCs) are an integral part of the tumor microenvironment (TME). MDSC's involvement in the TME starts as soon as the primary tumor starts to get its blood supply causing an immunosuppressive environment and tumor cell invasion, and then at the formation of premetastatic niche through full-blown metastasis in distal organs. All of these functions don't require physical interaction of MDSC as some of the MDSC's functions can be replicated by secreted exosomes (MDSC-derived exosomes), which can alter the microenvironment through cellular interaction by fusion with the plasma membrane and subsequent release of their cargo, consisting of proteins, soluble factors, lipids, DNAs, microRNAs (miRNAs), and RNAs. In this method paper, we explained how to isolate MDSC exosomes and how to use the exosome to observe immunosuppressive function. We also discussed how to measure the number of exosomes by nanoparticle tracking analysis. Additionally, we outlined how to measure the protein of exosomes as well as the types of protein by Bradford assay and membrane cytokine array respectively. We also provided instructions on how to utilize MDSC-derived exosomes to get knowledge about in vitro immune cell migration, scratch assay with the tumor cells, and in vivo effect of MDSC exosome along with T cell function and proliferation.

A comprehensive dataset for sentiment and emotion classification from Bangladesh e-commerce reviews.

In the rapidly evolving domain of e-commerce, analyzing customer feedback through reviews is crucial, particularly for understanding and enhancing consumer experience in the Bangladeshi market. Our comprehensive dataset, derived from two Bangladeshi e-commerce platforms, Daraz and Pickaboo, features a diverse collection of reviews in both Bengali and English, covering a broad range of products. These reviews are not only rich in linguistic variety but also encapsulate a spectrum of emotions, some even conveyed through emojis, offering a deep dive into consumer sentiment. Expert annotators have meticulously examined and categorized each review, classifying emotions into five distinct types - Happiness, Sadness, Fear, Anger, and Love - and sentiments into Positive (Happiness, Love) and Negative (Sadness, Anger, Fear) categories. This level of detailed annotation enables precise assessments of customer emotions and preferences, which are essential for evaluating and improving existing product offerings. Moreover, the insights gleaned from this dataset are invaluable for guiding future product development and uncovering new opportunities in the dynamic Bangladeshi market. Ultimately, this dataset not only serves as a significant resource for sentiment analysis using natural language processing (NLP) techniques but also contributes valuable insights into the unique consumer behavior patterns in Bangladesh, enriching the NLP community's understanding of diverse market dynamics.

Two rare flavonoid glycosides from Litsea glutinosa (Lour.) C. B. Rob.: experimental and computational approaches endorse antidiabetic potentiality.

BACKGROUND: Litsea glutinosa (Lour.) C. B. Rob. belongs to the Litsea genus and is categorized under the family of Lauraceae. The study aimed to investigate the phytoconstituents and pharmacological properties of methanol extract of leaves of Litsea glutinosa, focusing on antidiabetic activity via in vivo and in silico techniques. METHODS: Extensive chromatographic and spectroscopic techniques were applied to isolate and characterize the constituents from the L. glutinosa plant species. The antidiabetic activity was studied in streptozotocin-induced diabetes mice, and the computational study of the isolated compounds was carried out by utilizing AutoDock Vina programs. In addition, the pharmacokinetic properties in terms of absorption, distribution, metabolism and excretion (ADME) and toxicological profiles of the isolated compounds were examined via in silico techniques. RESULTS: In the present study, two flavonoid glycosides 4΄-O-methyl (2 ̋,4 ̋-di-E-p-coumaroyl) afzelin (1) and quercetin 3-O-(2 ̋,4 ̋-di-E-p-coumaroyl)-α-L-rhamnopyranoside (2) were isolated from the leaves of L. glutinosa and characterized by 1H and 13C NMR, COSY, HSQC, HMBC, and mass spectral data. Although compounds 1 and 2 have been reported twice from Machilis litseifolia and Lindera akoensis, and Machilis litseifolia and Mammea longifolia, respectively, this is the first report of this isolation from a Litsea species. Administering the methanolic extract of L. glutinosa at doses of 300 and 500 mg/kg/day to mice with diabetes induced by streptozotocin led to a significant decrease in fasting blood glucose levels (p < 0.05) starting from the 7th day of treatment. Besides, the computational study and PASS analysis endorsed the current in vivo findings that the both isolated compounds exerted higher binding affinities to human pancreatic α-amylase and aldose reductase than the conventional drugs. The in silico ADMET analysis revealed that the both isolated compounds have a favorable pharmacokinetic and safety profile suitable for human consumption. CONCLUSION: According to the current outcomes obtained from in vivo and in silico techniques, the leaf extract of L. glutinosa could be a natural remedy for treating diabetes, and the isolated phytoconstituents could be applied against various illnesses, mainly hyperglycemia. However, more investigations are required for extensive phytochemical isolation and pharmacological activities of these phytoconstituents against broader targets with exact mechanisms of action.

Morbidity and mortality of common femoral endarterectomy.

OBJECTIVE: Common femoral endarterectomy (CFE) comprises the current standard-of-care for symptomatic common femoral artery occlusive disease. Although it provides effective inflow revascularization via a single incision, it remains an invasive procedure in an often-frail patient population. The purpose of this retrospective clinical study was to assess the morbidity and mortality of CFE in a contemporary cohort. METHODS: Consecutive CFEs performed at a large, urban hospital were reviewed. Six-month mortality, local complications (hematoma, lymphatic leak, pseudoaneurysm, wound infection, and/or dehiscence), and systemic complications were analyzed using univariate and multivariate analyses. RESULTS: A total of 129 isolated CFEs were performed over 7 years for claudication (36%), rest pain (16%), tissue loss (29%), or acute on chronic limb ischemia (21%). Mean age was 75 ± 9 years, and 68% of patients were male. Comorbidities were prevalent, including coronary artery disease (54%), diabetes (41%), chronic pulmonary disease (25%), and congestive heart failure (22%). The majority of CFEs were performed under general anesthesia (98%) with patch angioplasty using bovine pericardium (73% vs 27% Dacron). Twenty-two patients (17%) sustained local complications following the procedure; their occurrence was significantly associated with obesity (P = .002) but no technical or operative factors. Nineteen patients (15%) sustained serious systemic complications; their occurrence was significantly associated with chronic limb-threatening ischemia (P < .001), and a high American Society of Anesthesiologists (ASA) class (P = .002). By 6 months, 17 patients (13%) had died. Being on dialysis, presenting with chronic limb-threatening ischemia, and being in a high ASA class at the time of operation were all associated with 6-month mortality; a high ASA class at the time of operation was independently predictive of mortality (odds ratio, 3.08; 95% confidence interval, 1.03-9.24; P = .044). CONCLUSIONS: Although commonly performed, CFE is not a benign vascular procedure. Disease presentation, anesthetic risk, and expected longevity play an important role in clinical outcomes. Evolving endovascular approaches to the common femoral artery could serve to reduce morbidity and mortality in the future.

ArsenicSkinImageBD: A comprehensive image dataset to classify affected and healthy skin of arsenic-affected people.

Compared to other popular research domains, dermatology got less attention among machine learning researchers. One of the main concerns for this problem is an inadequate dataset since collecting samples from the human body is very sensitive. In recent years, arsenic has emerged as a significant issue for dermatologists. Arsenic is a highly toxic substance found in the earth's crust whose small amounts can be very injurious to the human body. People who are exposed to arsenic for a long time through water and food can get cancer and skin lesions. With a view to contributing to this aspect, this dataset has been organized with the help of which the researchers can understand the impact of this contamination and design a solution using artificial intelligence. To the best of our knowledge, this is the first standard, easy-to-use, and open dataset of arsenic diseases. The images were collected from four places in Bangladesh, under the Department of Public Health Engineering, Chapainawabganj, where they are working on arsenic contamination. The dataset has 8892 skin images, with half of them showing people with arsenic effects and the other half showing mixed skin images that are not affected by arsenic. This makes the dataset useful for treating people with arsenic-related conditions. Eventually, this dataset can attract the attention of not only the machine learning researchers, but also scientists, doctors, and other professionals in the associated research field.

Differential Distribution of the DNA-PKcs Inhibitor Peposertib Selectively Radiosensitizes Patient-derived Melanoma Brain Metastasis Xenografts.

Radioresistance of melanoma brain metastases limits the clinical utility of conventionally fractionated brain radiation in this disease, and strategies to improve radiation response could have significant clinical impact. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is critical for repair of radiation-induced DNA damage, and inhibitors of this kinase can have potent effects on radiation sensitivity. In this study, the radiosensitizing effects of the DNA-PKcs inhibitor peposertib were evaluated in patient-derived xenografts of melanoma brain metastases (M12, M15, M27). In clonogenic survival assays, peposertib augmented radiation-induced killing of M12 cells at concentrations ≥100 nmol/L, and a minimum of 16 hours exposure allowed maximal sensitization. This information was integrated with pharmacokinetic modeling to define an optimal dosing regimen for peposertib of 125 mpk dosed just prior to and 7 hours after irradiation. Using this drug dosing regimen in combination with 2.5 Gy × 5 fractions of radiation, significant prolongation in median survival was observed in M12-eGFP (104%; P = 0.0015) and M15 (50%; P = 0.03), while more limited effects were seen in M27 (16%, P = 0.04). These data support the concept of developing peposertib as a radiosensitizer for brain metastases and provide a paradigm for integrating in vitro and pharmacokinetic data to define an optimal radiosensitizing regimen for potent DNA repair inhibitors.

Thiazolobenzamide-Naphthalene Hybrids as Potent Anticancer agents compared to Doxorubicin: Design, Synthesis, SAR, In-silico and Toxicity Analysis.

In order to determine whether thiazolobenzamide molecules connected to naphthalene could inhibit the growth of three different tumor cell lines, MCF7 (breast carcinoma), A549 (pulmonary carcinoma), and DU145 (prostatic adenocarcinoma) a novel series of ten molecules, designated TA 1-10, was designed, synthesized, and tested. Among these compounds, TA7 showed promising results against cell lines, especially showing exceptional efficacy against breast cancer. Antioxidant activity tests consistently showed the best performance from the TA7 molecule. Furthermore, when a dose of 50 to 500 mg/kg of the total mass of rats is given, the most effective chemical, TA7, did not exhibit any harmful effects during acute oral toxicity tests. The biochemical indicators (SGOT and SGPT) for hepatotoxicity associated with compound TA7 were found to be fairly similar to those of the control group. The findings from molecular docking, XP visualization, and MM-GBSA dG binding investigations are in agreement with the outcomes of in-vitro tests of antioxidant and anticancer capabilities. TA7 was the most effective compound among those that were docked; it bound free energy and had adequate properties for metabolism (biochemical processes), distribution (dispersion), absorption (assimilation), and excretion (elimination). This study found that the TA7 molecule, a thiazole ring system derivative connected to naphthalene, is to be a promising and possible anticancer agent and its efficacy may be further explored in clinical studies.

Perovskenes: two-dimensional perovskite-type monolayer materials predicted by first-principles calculations.

Inspired by the successful transfer of freestanding ultrathin films of SrTiO3 and BiFeO3 onto various substrates without any thickness limitation, in this study, using density functional theory (DFT), we assessed the structural stability of a group of two-dimensional perovskite-type materials which we call perovskenes. Specifically, we analyzed the stability of 2D SrTiO3, SrZrO3, BaTiO3, and BaZrO3 monolayers. Our simulations revealed that the 2D monolayers of SrTiO3, BaTiO3, and BaZrO3 are at least meta-stable, as confirmed by cohesive energy calculations, evaluation of elastic constants, and simulation of phonon dispersion modes. With this information, we proceeded to investigate the electronic, optical, and thermoelectric properties of these perovskenes. To gain insight into their promising applications, we investigated the electronic and optical properties of these 2D materials and found that they are wide bandgap semiconductors with significant absorption and reflection in the ultraviolet (UV) region of the electromagnetic field, suggesting them as promising materials for use in UV shielding applications. In addition, evaluating their thermoelectric factors revealed that these materials become better conductors of electricity and heat as the temperature rises. They can, hence, convert temperature gradients into electrical energy and transport electrical charges, which is beneficial for efficient power generation in thermoelectric devices. This work opens a new window for designing a novel family of 2D perovskite type materials termed perovskenes. The vast variety of different perovskite compounds and their variety of applications suggest deeper studies on the perovskenes materials for use in innovative technologies.

Angelica gigas extract inhibits acetylation of eNOS via IRE1α sulfonation/RIDD-SIRT1-mediated posttranslational modification in vascular dysfunction.

Angelica gigas NAKAI (AG) is a popular traditional medicinal herb widely used to treat dyslipidemia owing to its antioxidant activity. Vascular disease is intimately linked to obesity-induced metabolic syndrome, and AG extract (AGE) shows beneficial effects on obesity-associated vascular dysfunction. However, the effectiveness of AGE against obesity and its underlying mechanisms have not yet been extensively investigated. In this study, 40 high fat diet (HFD) rats were supplemented with 100-300 mg/kg/day of AGE to determine its efficacy in regulating vascular dysfunction. The vascular relaxation responses to acetylcholine were impaired in HFD rats, while the administration of AGE restored the diminished relaxation pattern. Endothelial dysfunction, including increased plaque area, accumulated reactive oxygen species, and decreased nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) Ser1177 phosphorylation, were observed in HFD rats, whereas AGE reversed endothelial dysfunction and its associated biochemical signaling. Furthermore, AGE regulated endoplasmic reticulum (ER) stress and IRE1α sulfonation and its subsequent sirt1 RNA decay through controlling regulated IRE1α-dependent decay (RIDD) signaling, ultimately promoting NO bioavailability via the SIRT1-eNOS axis in aorta and endothelial cells. Independently, AGE enhanced AMPK phosphorylation, additionally stimulating SIRT1 and eNOS deacetylation and its associated NO bioavailability. Decursin, a prominent constituent of AGE, exhibited a similar effect in alleviating endothelial dysfunctions. These data suggest that AGE regulates dyslipidemia-associated vascular dysfunction by controlling ROS-associated ER stress responses, especially IRE1α-RIDD/sirt1 decay and the AMPK-SIRT1 axis.

Brain-wide correspondence of neuronal epigenomics and distant projections.

Single-cell analyses parse the brain's billions of neurons into thousands of 'cell-type' clusters residing in different brain structures1. Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific cell types. Here we used epi-retro-seq2 to link single-cell epigenomes and cell types to long-distance projections for 33,034 neurons dissected from 32 different regions projecting to 24 different targets (225 source-to-target combinations) across the whole mouse brain. We highlight uses of these data for interrogating principles relating projection types to transcriptomics and epigenomics, and for addressing hypotheses about cell types and connections related to genetics. We provide an overall synthesis with 926 statistical comparisons of discriminability of neurons projecting to each target for every source. We integrate this dataset into the larger BRAIN Initiative Cell Census Network atlas, composed of millions of neurons, to link projection cell types to consensus clusters. Integration with spatial transcriptomics further assigns projection-enriched clusters to smaller source regions than the original dissections. We exemplify this by presenting in-depth analyses of projection neurons from the hypothalamus, thalamus, hindbrain, amygdala and midbrain to provide insights into properties of those cell types, including differentially expressed genes, their associated cis-regulatory elements and transcription-factor-binding motifs, and neurotransmitter use.

The selective cyclooxygenase-2 inhibitor NS398 ameliorates cisplatin-induced impairments in mitochondrial and cognitive function.

Chemobrain is a condition that negatively affects cognition in cancer patients undergoing active chemotherapy, as well as following chemotherapy cessation. Chemobrain is also known as chemotherapy-induced cognitive impairment (CICI) and has emerged as a significant medical contingency. There is no therapy to ameliorate this condition, hence identification of novel therapeutic strategies to prevent CICI is of great interest to cancer survivors. Utilizing the platinum-based chemotherapy cisplatin in an investigative approach for CICI, we identified increased expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in the adult mouse hippocampus, and in human cortical neuron cultures derived from induced pluripotent stem cells (iPSCs). Notably, administration of NS398, a selective COX-2 inhibitor, prevented CICI in vivo without negatively affecting the antitumor efficacy of cisplatin or potentiating tumor growth. Given that dysfunctional mitochondrial bioenergetics plays a prominent role in CICI, we explored the effects of NS398 in cisplatin-induced defects in human cortical mitochondria. We found that cisplatin significantly reduces mitochondrial membrane potential (MMP), increases matrix swelling, causes loss of cristae membrane integrity, impairs ATP production, as well as decreases cell viability and dendrite outgrowth. Pretreatment with NS398 in human cortical neurons attenuated mitochondrial dysfunction caused by cisplatin, while improving cell survival and neurite morphogenesis. These results suggest that aberrant COX-2 inflammatory pathways may contribute in cisplatin-induced mitochondrial damage and cognitive impairments. Therefore, COX-2 signaling may represent a viable therapeutic approach to improve the quality of life for cancer survivors experiencing CICI.

Comprehensive dataset of annotated rice panicle image from Bangladesh.

Bangladesh's economy is primarily driven by the agriculture sector. Rice is one of the staple food of Bangladesh. The count of panicles per unit area serves as a widely used indicator for estimating rice yield, facilitating breeding efforts, and conducting phenotypic analysis. By calculating the number of panicles within a given area, researchers and farmers can assess crop density, plant health, and prospective production. The conventional method of estimating rice yields in Bangladesh is time-consuming, inaccurate, and inefficient. To address the challenge of detecting rice panicles, this article provides a comprehensive dataset of annotated rice panicle images from Bangladesh. Data collection was done by a drone equipped with a 4 K resolution camera, and it took place on April 25, 2023, in Bonkhoria Gazipur, Bangladesh. During the day, the drone captured the rice field from various heights and perspectives. After employing various image processing techniques for curation and annotation, the dataset was generated using images extracted from drone video clips, which were then annotated with information regarding rice panicles. The dataset is the largest publicly accessible collection of rice panicle images from Bangladesh, consisting of 2193 original images and 5701 augmented images.

An Empirical Analysis of Sacha Inchi (Plantae: Plukenetia volubilis L.) Seed Proteins and Their Applications in the Food and Biopharmaceutical Industries.

Sacha Inchi (Plukenetia volubilis L.) is a plant native in the Amazon rainforest in South America known for its edible seeds, which are rich in lipids, proteins, vitamin E, polyphenols, minerals, and amino acids. Rural communities in developing nations have been using this plant for its health benefits, including as a topical cream for rejuvenating and revitalising skin and as a treatment for muscle pain and rheumatism. Although Sacha Inchi oil has been applied topically to soften skin, treat skin diseases, and heal wounds, its protein-rich seeds have not yet received proper attention for extensive investigation. Proteins in Sacha Inchi seeds are generally known to have antioxidant and antifungal activities and are extensively used nowadays in making protein-rich food alternatives worldwide. Notably, large-scale use of seed proteins has begun in nanoparticle and biofusion technologies related to the human health-benefitting sector. To extract and identify their proteins, the current study examined Sacha Inchi seeds collected from the Malaysian state of Kedah. Our analysis revealed a protein concentration of 73.8 ± 0.002 mg/g of freeze-dried seed flour. Employing liquid chromatography-tandem mass spectrometry (LC-MS/MS) and PEAKS studio analysis, we identified 217 proteins in the seed extract, including 152 with known proteins and 65 unknown proteins. This study marks a significant step towards comprehensively investigating the protein composition of Sacha Inchi seeds and elucidating their potential applications in the food and biopharmaceutical sectors. Our discoveries not only enhance our knowledge of Sacha Inchi's nutritional characteristics but also pave the way for prospective research and innovative advancements in the realms of functional food and health-related domains.

Prodrug Rewards in Medicinal Chemistry: An Advance and Challenges Approach for Drug Designing.

This article emphasizes the importance of prodrugs and their diverse spectrum of effects in the field of developing novel drugs for a variety of biological applications. Prodrugs are chemicals that are supplied inactively, but then go through enzymatic and chemical transformation in vivo to release the active parent medication that can have the desired pharmacological effect. By adding an inactive chemical moiety, prodrugs are improved in a number of ways that contribute to their potency and durability. For the purpose of illustrating the usefulness of the prodrug approach, this review covers examples of prodrugs that have been made available or are now undergoing human trials. Additionally, it included lists of the most common functional groups, carrier linkers, and reactive chemicals that can be used to create prodrugs. The current study also provides a brief introduction, several chemical methods and modifications for creating prodrugs and mutual prodrugs, as well as an explanation of recent advancements and difficulties in the field of prodrug design. The primary chemical carriers employed in the creation of prodrugs, such as esters, amides, imides, NH-acidic carriers, amines, alcohols, carbonyl, carboxylic, and azo-linkages, are also discussed. This review also discusses glycosidic and triglyceride mutually activated prodrugs, which aim to deliver the drugs after bioconversion at the intended site of action. The article also discusses the extensive chemistry and wide variety of applications of recently approved prodrugs, such as antibacterial, anti-inflammatory, cardiovascular, antiplatelet, antihypertensive, atherosclerotic, antiviral, etc. In order to illustrate the prodrug and mutual drug concept's various applications and highlight its many triumphs in overcoming the formulation and delivery of problematic pharmaceuticals, this work represents a thorough guide that includes the synthetic moiety for the reader.

Exploring therapeutic potential of Woodfordia fruticosa (L.) Kurz leaf and bark focusing on antioxidant, antithrombotic, antimicrobial, anti-inflammatory, analgesic, and antidiarrheal properties.

Background and Aims: The study aimed to evaluate the pharmacological properties of methanolic extracts of leaves and barks of Woodfordia fruticosa (L.) Kurz (family: Lythraceae) focusing on antioxidant, thrombolytic, anti-inflammatory, antibacterial, analgesic, and antidiarrheal effects. Methods: 1,1-Diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay, clot lysis, disc diffusion, and membrane stabilizing methods were employed to assess in vitro antioxidant, thrombolytic, antibacterial, and anti-inflammatory properties of the leaf and bark methanolic extracts (ME) of W. fruticosa and different organic solvents, that is, petroleum ether (PE), dichloromethane (DCM), chloroform (CL), and aqueous (AQ) fractions. In addition, in vivo central and peripheral analgesic and antidiarrheal activities of both crude extracts were evaluated at two doses (200 and 400 mg/kg of body weight [bw]). Results: All the extracts and fractions showed promising antioxidant properties by scavenging DDPH free radicals with IC50 of 6.11-20.79 µg/mL. AQ fraction (41.24%) of leaves and ME (44.90%) of bark exerted notable in vitro thrombolytic activity. The CL fraction of leaves and AQ fraction of the bark showed 43.16% and 45.37% inhibition of RBC hemolysis, respectively, compared to the inhibition of RBC hemolysis by aspirin in a hypotonic-induced membrane stabilizing assay. Besides, both extracts were observed to provide significant (p < 0.001) central and peripheral analgesic responses at both doses of 200 and 400 mg/kg bw. Furthermore, both doses of bark extract (p < 0.001) and the 400 mg/kg bw of leaf extract (p < 0.05) were observed to possess statistically significant antidiarrheal activity. Additionally, in an in vivo acute toxicity investigation, both extracts had a median lethal dose (LD50) greater than 5000 mg/kg bw, indicating their safety level. Conclusion: The current study proves the ethnomedicinal uses of W. fruticosa; however, further studies are required for phytochemical screening to isolate the responsible bioactive compounds and discover the lead molecules from the plant species.

Chemico-pharmacological and computational studies of Ophiorrhiza fasciculata D. Don and Psychotria silhetensis Hook. f. focusing cytotoxic, thrombolytic, anti-inflammatory, antioxidant, and antibacterial properties.

The current study sought to examine the pharmacological potentials of crude methanolic extracts of Ophiorrhiza fasciculata and Psychotria silhetensis, as well as their various solvent fractionates, with a focus on cytotoxic, thrombolytic, membrane stabilizing, antioxidant, and antibacterial activities via in vitro and in silico approaches. The extensive chromatographic and spectroscopic analyses confirmed and characterized two compounds as (±)-licarin B (1) and stigmasterol (2) from O. fasciculata and P. silhetensis, respectively. Petroleum ether soluble fraction of O. fasciculata and the aqueous soluble fraction of P. silhetensis showed the lowest 50% lethal concentrations (1.41 and 1.94 µg/mL, respectively) in brine shrimp bioassay. Likewise, petroleum ether soluble fraction of O. fasciculata and aqueous soluble fraction of P. silhetensis showed the highest thrombolytic activity with 46.66% and 50.10% lyses of the clot, respectively. The methanol and dichloromethane soluble fractions of O. fasciculata reduced erythrocyte hemolysis by 64.03% and 37.08%, respectively, under hypotonic and heat-induced conditions, compared to 81.97% and 42.12% for standard acetylsalicylic acid. In antioxidant activity test, aqueous soluble fraction O. fasciculata (IC50 = 7.22 µg/mL) revealed promising antioxidant potentialities in comparison to standard butylated hydroxytoluene (IC50 = 21.20 µg/mL). In antibacterial screening, chloroform, and dichloromethane soluble fractions of P. silhetensis showed a mild antibacterial activity compared with the standard drug ciprofloxacin. Additionally, the molecular docking study corroborated the current in vitro findings, and the isolated two constituents had higher binding affinities toward epidermal growth factor receptor, tissue plasminogen activator, vFLIP-IKK gamma stapled peptide dimer, glutathione reductase, and dihydrofolate reductase enzyme than their corresponding standard drugs. In addition, the both isolated compounds exerted favorable pharmacokinetics (absorption, distribution, metabolism, excretion) and toxicological profiles with drug-like qualities in computational-based ADMET and drug likeliness analyses. The current research suggests that both plants have potential as a natural treatment for treating thrombosis, inflammation, and oxidative stress. However, more thorough research is required to thoroughly screen for phytochemicals and pinpoint the precise mechanisms of action of the bioactive metabolites derived from these plants against a broad range of molecular targets.

The Role of Reactive Oxygen Species, Inflammation, and Endoplasmic Reticulum Stress Response in the Finasteride Protective Effect against Benign Prostate Hyperplasia.

PURPOSE: Benign prostate hyperplasia (BPH) is a common age-related chronic condition. Its pathogenesis involves androgen imbalance, inflammation, oxidative stress, and endoplasmic reticulum (ER) stress. This study aims to assess the protective effect of finasteride, a 5α-reductase inhibitor, against testosterone propionate (TP)-induced BPH in rats and explore its potential mechanism of action. MATERIALS AND METHODS: TP-induced BPH rats received either saline or finasteride (1 mg/kg) orally once a day for 7 weeks. Prior to sacrificing the animals, blood samples were collected. After sacrifice, prostate and tissue around the prostate were dissected from seminal vesical for further analysis. Body weight, prostate weight, dihydrotestosterone (DHT), 5α-reductase type 2 (5-AR2), and prostate-specific antigen (PSA) levels were measured. In addition, HIF-1α, VEGF, MMP-2 expressions in prostate, oxidative stress, inflammation, and ER stress responses were analyzed to understand the mechanism of action of finasteride. RESULTS: Finasteride administration inhibited prostate enlargement, DHT, 5-AR2, and PSA levels in BPH rats. Additionally, finasteride inhibited angiogenesis markers such as HIF-1α, VEGF, and MMP-2. Moreover, components of oxidative stress, inflammation, and ER stress responses were significantly regulated by finasteride treatment. CONCLUSIONS: This study suggests that finasteride prevents BPH-associated symptoms by regulating angiogenesis, reactive oxygen species, ER stress responses, and inflammation, another mechanism to explain the effect of the 5α-reductase against BPH.