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Dietary phytochemicals are important contributors to various diseases prevention, due to their interactions with CYP family enzymes. Safranal and crocin are bioactive compounds present in Crocus sativus L., commonly known as saffron. In present study, we prepared saffron extract and performed its HPLC phytochemical analysis for safranal and crocin content. We have also determined the effect of crocin and safranal on the metabolic activity of CYP2C9 by using in-silico approaches such as 3D-QSAR molecular docking and pharmacophore mapping studies. The extraction method was simple and the content of crocin and safranal was obtained to be 26.45 ± 0.03 and 11.0 ± 0.02 mg/g of saffron respectively. The predictivity of the best 3D-QSAR model developed for flavonoid derivatives was found to be 91.3%. The predicted activities of crocin and safranal for CYP2C9 were found to be 7.805 and 7.120 respectively. Further, docking studies revealed that crocin bonded CYP2C9 protein with binding affinity -9 kcal/mol, whereas, co-crystallized standard flurbiprofen bonded with 8.2 kcal/mol only. The results obtained in the present study furnish primary data for future in vitro and in vivo herb-drug interaction studies involving CYP2C9 enzyme. [ABSTRACT FROM AUTHOR]

Context: Rumex vesicarius L. (Polygonaceae), an edible plant, is reported to have many bioactive phytochemicals, especially flavonoids and anthraquinones with antioxidant and detoxifying properties. Objective: This study evaluated the methanolic extract of R. vasicarius (MERV) for hepatoprotective activity in rats against CCl4-induced liver damage. Materials and methods: The whole plant extract was prepared and investigated for its hepatoprotective activity. Rats were pretreated with MERV (100 and 200 mg/kg, p.o.) for 7 d prior to the induction of liver damage by CCl4. Animals were then sacrificed 24 h after CCl4 administration for the biochemical (AST, ALT, and ALP activity in serum; lipid peroxidation (LPO) and glutathione (GSH) levels in liver tissue) and histological analyses. Results: CCl4-induced hepatotoxicity was confirmed by an increase ( p < 0.05) in serum AST (4.55-fold), ALT (3.51-fold), and ALP (1.82-fold) activities. CCl4-induced hepatotoxicity was also manifested by an increase ( p < 0.05) in LPO (3.88-fold) and depletion of reduced glutathione (3.14-fold) activity in liver tissue. The multiple dose MERV administration at 200 mg/kg showed promising hepatoprotective activity as evident from significant decrease levels of serum AST (230.01 ± 13.21), serum ALT (82.15 ± 5.01), serum ALP (504.75 ± 19.72), hepatic LPO (3.38 ± 0.33), and increased levels of hepatic glutathione (0.34 ± 0.04) towards near normal. Further, biochemical results were confirmed by histopathological changes as compared with CCl4-intoxicated rats. Discussion and conclusion: The results obtained from this study indicate hepatoprotective activity of Rumex plant against CCl4-induced liver toxicity; hence, it can be used as a hepatoprotective agent. [ABSTRACT FROM AUTHOR]

The present study evaluated the cardioprotective potential of ethanol extract of Embelia ribes Burm. (Myrsinaceae) fruits on left anterior descending coronary artery ligation (LAD)-induced myocardial infarction in albino rats. In open-chest chloral hydrate (400 mg/kg, i.p.) anesthetized rats, the left anterior descending coronary artery was occluded for 30 min followed by 90 min of reperfusion. Vehicle (1% Tween 80 in distilled water) or ethanol Embelia ribes extract (100 and 200 mg/kg, orally) was administered for 7 days (pre-treatment). In the vehicle-treated group, ischemic-reperfusion injury (IRI) was evidenced by depression of hemodynamic function (heart rate), raised levels of serum lactate dehydrogenase (LDH) and myocardial thiobarbituric acid reactive substances (TBARS) levels and depletion of endogenous myocardial antioxidants (glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)) and Na-K-ATPase levels, as compared to sham rats. Pre-treatment with ethanol Embelia ribes extract prevented 1) loss of myocardial hemodynamic function, 2) rise in serum LDH and myocardial TBARS levels, and 3) depletion of myocardial endogenous antioxidants and Na-K-ATPase levels. The results of the present study, suggests that ethanol Embelia ribes extract treatment enhances the antioxidant defense against LAD-induced ischemic-reperfusion injury in rats and exhibits cardioprotective property. [ABSTRACT FROM AUTHOR]

Baricitinib (BTB) is an orally administered Janus kinase inhibitor, therapeutically used for the treatment of rheumatoid arthritis. Recently it has also been approved for the treatment of COVID-19 infection. In this study, four different BTB-loaded lipids (stearin)-polymer (Poly(d,l-lactide-co-glycolide)) hybrid nanoparticles (B-PLN1 to B-PLN4) were prepared by the single-step nanoprecipitation method. Next, they were characterised in terms of physicochemical properties such as particle size, zeta potential (ζP), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL). Based on preliminary evaluation, the B-PLN4 was regarded as the optimised formulation with particle size (272 ± 7.6 nm), PDI (0.225), ζP (−36.5 ± 3.1 mV), %EE (71.6 ± 1.5%) and %DL (2.87 ± 0.42%). This formulation (B-PLN4) was further assessed concerning morphology, in vitro release, and in vivo pharmacokinetic studies in rats. The in vitro release profile exhibited a sustained release pattern well-fitted by the Korsmeyer–Peppas kinetic model (R2 = 0.879). The in vivo pharmacokinetic data showed an enhancement (2.92 times more) in bioavailability in comparison to the normal suspension of pure BTB. These data concluded that the formulated lipid-polymer hybrid nanoparticles could be a promising drug delivery option to enhance the bioavailability of BTB. Overall, this study provides a scientific basis for future studies on the entrapment efficiency of lipid-polymer hybrid systems as promising carriers for overcoming pharmacokinetic limitations. [ABSTRACT FROM AUTHOR]

Sirtuins or Sir (Silent information regulator) are NAD+-dependent enzymes playing an important part in the pathogenesis and treatment of various disorders. They have ubiquitously expressed protein deacetylases. They are implicated in several cellular activities like DNA repair, cellular metabolism, mitochondrial function, and inflammation. Deletion of sirtuin protein, SIRT1 in the organs like brain, heart, liver and pancreas can cause inflammation and increases the level of free radical ions causing oxidative stress. Inflammation and oxidative stress are closely associated with pathophysiological events in many chronic diseases, like diabetes, cancer, cardiovascular, osteoporosis, and neurodegenerative diseases. Modulation of SIRT1 gene expression might help in preventing the progression of chronic diseases related to the brain, heart, liver, and pancreas. SIRT2 proteins play an essential role in tumorigenesis, including tumor-suppressing and tumor-promoting functions. Sirtuin activators are molecules that upregulate the activity of Sirtuins in the body. Their multifaceted uses have surprised the global scientific community. They are found to control obesity, lower cardiac risks, battle cancer, etc. This article provides an update on the pharmacological effect of SIRT1 and SIRT 2 proteins, their activators and inhibitors, and their molecular mechanism. It provides novel insights for future research in targeted therapy and drug development. [ABSTRACT FROM AUTHOR]

Monocarboxylate transporter 4 (MCT-4) is involved in various metabolic processes which are crucial in maintaining cellular pH and energy metabolism, and thus influence the tumor microenvironment. The study is aimed to rationally design effective Small interfering RNA (siRNA) that can silence MCT-4. We utilized a comprehensive workflow integrating multiple tools such as siDirect version 2.0, Oligowalk and i-score designer, to evaluate sequence features and predict target site accessibility, Guanine-Cytosine (GC) content and thermodynamic stability. Five (M1, M2, M3, M4 and M5) siRNAs sequences were retrived and subjected to further scrutiny on the account of off-target elimation, sequence conservation, secondary structure formation, and thermodynamic properties. The M1 demonstrated off targets and the M2 sequence showed secondry conformation and therefore M3, M4 and M5 were considered for further evaluation. Additionally, molecular docking and simulations (50 ns) were conducted with human Argonaute 2 protein (h-Arg-2). The post- molecular dynamics (MD) analysis revealed M4 (5'UUGAAGAAGACACUGACGG3') as a most appropriate siRNA candidate agsint MCT-4 on the basis of Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), and H-Bond results. The Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) analysis was also performed to further validate the selected siRNA candidates, which further affirmed M4 (5'UUGAAGAAGACACUGACGG3') as an potential candidate for future in-vitro and in-vivo evaluation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The biotechnology field has witnessed rapid advancements, leading to the development of numerous proteins and peptides (PPs) for disease management. The production and isolation of bioactive milk peptides (BAPs) involve enzymatic hydrolysis and fermentation, followed by purification through various techniques such as ultrafiltration and chromatography. The nutraceutical potential of bioactive milk peptides has gained significant attention in nutritional research, as these peptides may regulate blood sugar levels, mitigate oxidative stress, improve cardiovascular health, gut health, bone health, and immune responses, and exhibit anticancer properties. However, to enhance BAP bioavailability, the encapsulation method can be used to offer protection against protease degradation and controlled release. This article provides insights into the composition, types, production, isolation, bioavailability, and health benefits of BAPs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Hypoxia inducible factors (HIFs) are heterodimeric proteins that belong to a small group of transcription factors, which mainly regulates transcription of genes under hypoxic conditions. Particularly, oxygen sensing subunit of HIF-1α is a predominant subtype that heterodimerizes with oxygen-independent HIF-1β subunit, to trigger the transcription of hypoxia responsive genes. Due to poor supply of blood and rapid division of cancerous cells, tumor microenvironment exhibits low oxygen condition and therefore increased levels of HIF-1α. One of the promising therapeutic strategies to cancer is modulation of HIF-1α signaling pathway. Small interfering RNA (siRNA) mediated downregulation of HIF-1α has been reported to prevent growth and progression of various types of cancer and holds great promise in the cancer treatment. In this study, computational approaches were used to design potential siRNAs targeting HIF-1α and investigate their interaction with the human argonaute-2 (hAgo2). Molecular dynamic simulation of HIF-1α siRNAs-hAgo2 complexes revealed key interactions required for the efficient binding of guide strand to hAgo2 protein. Two siRNAs (S2 and S5) exhibiting strong binding with hAgo2 were further considered. Subsequently, we transfected the MCF-7 cell line with both standard HIF-1α and our designed siRNAs (S2 and S5). Following transfection, translation changes in the MCF-7 cells were assessed through western blotting. S2 and S5 efficiently reduced the expression of HIF-1α in hypoxic conditions. The aim of the present study is to understand the siRNA-hAgo2 interaction. It is also focused on the desiging of effective siRNA against HIF-1α., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Lung cancer (LC) ranks second most prevalent cancer in females after breast cancer and second in males after prostate cancer. Based on the GLOBOCAN 2020 report, India represented 5.9% of LC cases and 8.1% of deaths caused by the disease. Several clinical studies have shown that LC occurs because of biological and morphological abnormalities and the involvement of altered level of antioxidants, cytokines, and apoptotic markers. In the present study, we explored the antiproliferative activity of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues against LC using in-vitro, in-silico, and in-vivo models. In-vitro screening against A549 cells revealed compounds 9B (8-methoxy-5-(3,4,5-trimethoxyphenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) and 12B (5-(4-chlorophenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) as potential pyrimidine analogues against LC. Compounds 9B and 12B were docked with different molecular targets IL-6, Cyt-C, Caspase9, and Caspase3 using AutoDock Vina 4.1 to evaluate the binding affinity. Subsequently, in-vivo studies were conducted in albino Wistar rats through ethyl-carbamate (EC)- induced LC. 9B and 12B imparted significant effects on physiological (weight variation), and biochemical (anti-oxidant [TBAR's, SOD, ProC, and GSH), lipid (TC, TG, LDL, VLDL, and HDL)], and cytokine (IL-2, IL-6, IL-10, and IL-1β) markers in EC-induced LC in albino Wistar rats. Morphological examination (SEM and H&E) and western blotting (IL-6, STAT3, Cyt-C, BAX, Bcl-2, Caspase3, and caspase9) showed that compounds 9B and 12B had antiproliferative effects. Accordingly, from the in-vitro, in-silico, and in-vivo experimental findings, we concluded that 9B and 12B have significant antiproliferative potential and are potential candidates for further evaluation to meet the requirements of investigation of new drug application., (© 2024. The Author(s).)

Anemia is a severe health issue that affects around one-third of the global population. Therefore, the present study aims to conduct a bibliometric analysis to investigate the research trends regarding advancements on iron formulations in treating iron deficiency anemia via oral or parenteral route. This study adopts thematic and bibliometric methods on existing research on novel iron formulations. It also provides perspective into the existing understanding on treatment strategies for iron deficiency anemia. This study is conducted on 543 papers on various ferrous and ferric formulations used in the treatment of iron deficiency anemia. The study period is from 1977 to 2022, and the papers are identified from the Scopus database. The bibliometric analysis was carried out using the R tool's Bibliometrix package. The study discusses performance analysis, including annual publications, geographic analysis, relevant affiliations, journal analysis, and citation analysis. In addition, the conceptual structure, including the co-occurrence network, thematic map, thematic evolution, intellectual structure highlighting co-citation analysis, and social structure depicting the collaboration network and collaboration world map, are presented. The results showed increased research on formulation strategies for the treatment of iron deficiency anemia from 2010 onwards. The top 5 contributing countries are the USA, Italy, India, Germany, and the UK, and peer-reviewed journals from the area of nutrition. The most trending areas of study are iron deficiency anemia in pregnancy, chronic kidney diseases, inflammatory bowel diseases, and various intravenous formulations used in its treatment. The authors from Europe collaborate the most with authors from other countries. The study concludes that a safer and more effective iron formulation is needed to reduce the prevalence of anemia. The findings of the study are helpful in advancing research on innovative formulations for treating iron deficiency anemia. The insights from the study are helpful to policymakers in designing specific health policies and investing more in research and development of novel formulations for the treatment of iron deficiency anemia., Competing Interests: The authors declare no conflict of interest. The items expressed in this article are personal and do not represent to Lupin Research Park., (© 2024 The Authors.)

Pulmonary diseases like asthma, chronic obstructive pulmonary disorder, lung fibrosis, and lung cancer pose a significant burden to global human health. Many of these complications arise as a result of exposure to particulate matter (PM), which has been examined in several preclinical and clinical trials for its effect on several respiratory diseases. Particulate matter of size less than 2.5 μm (PM 2.5 ) has been known to inflict unforeseen repercussions, although data from epidemiological studies to back this are pending. Conventionally utilized two-dimensional (2D) cell culture and preclinical animal models have provided insufficient benefits in emulating the in vivo physiological and pathological pulmonary conditions. Three-dimensional (3D) structural models, including organ-on-a-chip models, have experienced a developmental upsurge in recent times. Lung-on-a-chip models have the potential to simulate the specific features of the lungs. With the advancement of technology, an emerging and advanced technique termed microfluidic organ-on-a-chip has been developed with the aim of identifying the complexity of the respiratory cellular microenvironment of the body. In the present Review, the role of lung-on-a-chip modeling in reproducing pulmonary complications has been explored, with a specific emphasis on PM 2.5 -induced pulmonary complications., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Postpartum depression (PPD) is a challenging psychological disorder faced by 10-30% of mothers across the globe. In India, it occurs among 22% of mothers. Its aetiology and pathophysiology aren't fully understood as of today but multiple theories on the interplay of hormones, neurotransmitters, genetics, epigenetics, nutrients, socio-environmental factors, etc. exist. Nutrients are not only essential for the synthesis of neurotransmitters, but they may also indirectly influence genomic pathways that methylate DNA, and there is evidence for molecular associations between nutritional quality and psychological well-being. Increased behavioural disorders have been attributed to macro- and micronutrient deficiencies, and dietary supplementation has been effective in treating several neuropsychiatric illnesses. Nutritional deficiencies occur frequently in women, especially during pregnancy and breastfeeding. The aim of this study was to perform a comprehensive literature review of evidence-based research in order to identify, gather and summarize existing knowledge on PPD's aetiology, pathophysiology, and the role of nutrients in its prevention as well as management. The possible mechanisms of action of nutrients are also presented here. Study findings show that the risk of depression increases when omega-3 fatty acid levels are low. Both fish oil and folic acid supplements have been used to effectively treat depression. Antidepressant efficacy is lowered by folate insufficiency. Folate, vitamin B12, iron, etc. deficiencies are more prevalent in depressed people than in non-depressed people. Serum cholesterol levels and plasma tryptophan levels are found to be inversely correlated with PPD. Serum vitamin D levels were associated inversely with perinatal depression. These findings highlight the importance of adequate nutrition in the antepartum period. Given that nutritional therapies can be affordable, safe, simple to use, and are typically well-accepted by patients, more focus should be placed on dietary variables in PPD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Antibiotics and immunotherapies possess unavoidable adverse effects that hinder sepsis management. Herbal drugs have demonstrated potential immunomodulatory properties vital for sepsis treatment. We hypothesized in the present study that the use of Carica papaya leaves extract had the potential to improve survival and modulate immune cytokine release during sepsis. Animals were subjected to cecal ligation and puncture (CLP) to induce sepsis. Septic rats divided into 10 groups received ethanol extract of C. papaya leaves (50 and 100 mg/kg), imipenem (120 mg/kg) and cyclophosphamide (CP, 10 mg/kg). To investigate the immunomodulatory potentials of EE, cytokine levels like interleukin (IL-6), tumor necrosis factor (TNF-α), and IL-10 along with hematological and biochemical parameters were analyzed. Our results exhibited improved survival rates concerning ethanol extract treatment alone and in combination with imipenem and CP (100%) as compared to the CLP group (33.3%) on day 7 post-surgery. The combination treatment of ethanol extract with imipenem and CP significantly (P < 0.001) ameliorated cytokine levels and hematological and biochemical parameters in septic rats. A histopathological examination suggested improved liver and kidney tissue condition after combination treatment as compared to the CLP group. Therefore, it was concluded that combination therapy of extract with imipenem and CP improved survival rates and marked immunomodulatory potential in septic rats compared to monotherapy. The findings suggested the use of a mixture of these drugs in clinical settings to treat sepsis., Competing Interests: Conflict of interestThe authors of the present study declare no conflict of interest., (© King Abdulaziz City for Science and Technology 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The study was aimed to evaluate in vitro antioxidant, α-amylase inhibitory and in vivo antidiabetic activities of Myrica salicifolia root extracts. The powdered roots of M. salicifolia were extracted with 80% methanol and then dried. The dried extract was further fractionated into chloroform, ethyl acetate, butanol and aqueous fractions. The phytochemical screening of the crude extract was performed using standard chemical identification tests. The antioxidant activity of the extracts was determined by in vitro method using 2,2-diphenyl-1-picrylhydrazyl (DPPH) as radical scavenging reagent. The in vitro α-amylase inhibitory activity was performed using the chromogenic3,5-dinitrosalicylic (DNSA) method. The antidiabetic activity of M. salicifolia root crude extract (200, 400 and 600 mg/kg) and fractions (400 mg/kg) were evaluated in normal, glucose loaded hyperglycemic and streptozotocin (STZ)-induced diabetic mice. The crude root extract of M. salicifolia showed strong DPPH radical scavenging activity (IC50 = 4.54µg/ml) which was comparable with the standard antioxidant, ascorbic acid. In α-amylase inhibitory activity, the crude extract and butanol fraction showed highest enzyme inhibition. In the antidiabetic activity, daily administration of the crude extract, aqueous and butanol fractions for fifteen days showed highest significant reduction in fasting blood glucose level (BGL) compared to diabetic control in STZ-induced diabetic mice model. The root extract and fractions of M. salicifolia exhibited significant antihyperglycemic, α-amylase inhibitory and antioxidant activity with no sign of toxicity. The antidiabetic effect of the plant could be due to the synergistic effect of various classes of constituents present in the root part of the plant.