Introduction: Psorospermum febrifugum is traditionally used in Africa for the treatment of inflammation andmalaria. This study aimed to isolate and characterize a bioactive compound from its leaves, evaluate its anti-inflammatory activity, assess the antiplasmodial activity of the CH2Cl2/MeOH crude extract, and predict potential molecular targets through docking studies.Methods: A bioactive compound was isolated from the leaves using chemical, chromatographic, and spectroscopictechniques. Anti-inflammatory activity was evaluated by inhibition of egg albumin and bovine serum albumin (BSA) denaturation. The CH2Cl2/MeOH crude extract was tested against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum strains using the SYBR Green assay. Molecular docking of the isolated compound was performed against BSA (4JK4), cyclooxygenase-1 (COX-1), P. falciparum lactate dehydrogenase(PfLDH), and dihydroorotate dehydrogenase (PfDHODH).Results: Apigenin-7-O-glucuronide was isolated and is reported here for the first time from P. febrifugum. Thecompound exhibited strong anti-inflammatory activity, with IC50 values of 40.61 ± 0.92 and 87.62 ± 0.60 μg/mLagainst egg albumin and BSA denaturation, respectively. The crude extract showed moderate antiplasmodialactivity against 3D7 and Dd2 strains, with IC50 values of 44.61 ± 0.08 and 49.08 ± 0.10 μg/mL, respectively. Dockinganalysis suggested favorable interactions of apigenin-7-O-glucuronide with PfLDH, PfDHODH, BSA, and COX-1,indicating potential anti-inflammatory and antiplasmodial mechanisms.Conclusion: These findings provide scientific support for the traditional use of P. febrifugum in treating inflammation and malaria and identify apigenin-7-O-glucuronide as a promising bioactive constituent warranting further pharmacological investigation.
Introduction: Toxic hepatitis is characterized by enhanced oxidative stress and disruption of antioxidant defense mechanisms in the liver mitochondria. In this study, we investigated the effects of polyphenolic extracts (Helmar- 1 and Helmar-2) obtained from Helichrysum maracandicum on mitochondrial antioxidant systems in rats with experimentally induced toxic hepatitis. Methods: Experimental toxic hepatitis was established in rats through intraperitoneal administration of carbon tetrachloride (CCl₄) diluted in olive oil (50%, 1 mL/kg), administered twice weekly over a two-week period. Liver injury was verified by elevated plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The animals were subsequently treated with Helmar-1 and Helmar-2 extracts at a dose of 20 mg/kg per day for 10 consecutive days. The activities of key antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), malondialdehyde (MDA) content, and mitochondrial respiration and oxidative phosphorylation parameters (V₂, V₃, V₄, RCR, and ADP/O ratio) were assessed in liver mitochondria. Results: Treatment with both Helmar-1 and Helmar-2 extracts resulted in a significant enhancement of antioxidant enzyme activities, a marked reduction in MDA levels, and substantial improvement in mitochondrial respiration and oxidative phosphorylation parameters compared to untreated toxic hepatitis groups. Conclusion: Overall, these results confirm that Helichrysum maracandicum polyphenol extracts improve mitochondrial respiration, oxidative phosphorylation efficiency, antioxidant defense, and membrane stability in toxic hepatitis.
Introduction: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide, with a five-year survival rate of only 19%. Although Sorafenib is the primary systemic therapy, its limited efficacy and complex interactions with signaling pathways highlight the need for multi-target drugs. Methods: This study evaluates the anti-cancer properties of selected phytochemicals against six key HCC target proteins, utilizing sorafenib tosylate as a positive control. Molecular docking was performed to evaluate binding affinities and interactions, and ADME/T predictions were generated to estimate drug-like properties. The topranking candidates were further evaluated using 100-ns molecular dynamics simulations to analyze conformational stability, protein-ligand interactions, and residue mobility. Results: Silymarin (SA) emerged as the most effective compound, demonstrating greater predicted inhibitory activity than Sorafenib. SA showed high binding affinity for target proteins 6HH1 (−9.9 kcal/mol) and 1CM8 (−9.6 kcal/mol). Molecular dynamics simulations also revealed increased stability of the SA-protein complexes, particularly for the 1CM8-SA complex, which maintained high conformational stability. The root-mean-square deviation (RMSD) value was found to be around 2.1 Å, and the root-mean-square fluctuation (RMSF) values were below 3 Å, indicating lower protein flexibility compared to both the native and sorafenib-bound complexes. Conclusion: These computational findings provide a strong theoretical basis for Silymarin’s efficacy as a highly potent, multi-targeted therapeutic agent against HCC. The improved stability and binding properties of Silymarin compared with Sorafenib provide a strong rationale for advancing this compound into preclinical and clinical studies.
Introduction: Withania somnifera, commonly known as Ashwagandha, is one of the most widely prescribed plants in the Indian system of traditional medicine. Its roots are believed to impart comprehensive health benefits supporting lifespan and healthspan through their anti-stress, immunomodulatory, and neuroprotective activity. Scientific validation of its claimed biological effects is warranted. Methods: The nematode worm Caenorhabditis elegans was challenged with heat or certain neurotoxic/mitotoxic chemical stressors, and worm activity (healthspan) was compared between W. somnifera root extract (WSRE)- exposed and control worm populations through an automated worm tracker. Results: Previous exposure of worms to WSRE conferred prophylactic benefit on them in the face of subsequent challenge with rotenone, MnCl2, or levamisole. Worms pre-exposed to either of these toxins were able to recover faster in the presence of WSRE. This extract was also able to reduce the susceptibility of wild-type worms to heatinduced paralysis and that of transgenic worms to beta-amyloid-mediated paralysis. Conclusions: W. somnifera root extract improved the ability of C. elegans to withstand and recover from multiple stressors, consistent with its adaptogenic-like effects mentioned in traditional medicine. WSRE conferred protection on this worm against multiple stressors acting through different toxicological mechanisms. Our results support the candidature of W. somnifera roots as a potent nutraceutical. However, the underlying molecular targets and pathways remain to be elucidated.
Introduction: Free radicals are key contributors to several diseases, including cancer, inflammation, pain, and neurodegenerative disorders such as Alzheimer’s disease. Due to the limitations and adverse effects of synthetic antioxidants, naturally occurring phytochemicals offer safer, more sustainable alternatives. This study investigates the antioxidant potential of twigs of Combretum molle R. Br. ex G. Don through integrated experimental and computational approaches. Methods: Compounds were isolated using chromatographic methods, and their structures established by 1Dand 2D-NMR, HR-ESI-MS, and comparison with reported data. Antioxidant activity was assessed through DPPH radical scavenging and FRAP assays, while molecular docking against xanthine oxidase (PDB: 1FIQ) explored possible mechanisms beyond direct radical scavenging. Results: A new macrocyclic bisbibenzyl derivative, combrebisbibenzyl A (1), was identified along with corosolic acid (2), maslinic acid (3), a mixture of asiatic acid (4) and arjunolic acid (5), combregenin (6), and β-sitosterol glucoside (7). The MeOH extract and EtOAc fraction showed notable DPPH scavenging activity (IC₅₀ = 170.21 and 197.41 μg/mL) and strong reducing power (65.04 ± 1.07 and 67.42 ± 0.82 mM Vit C/g). Among the isolated compounds, combrebisbibenzyl A (1) displayed the strongest radical scavenging effect (IC₅₀ = 175.64 μg/mL) and high reducing capacity (57.46 ± 0.42 mM Vit C/g). Docking indicated favorable interactions for all compounds, with combrebisbibenzyl A (1) showing the highest affinity (–9.1 kcal/mol), outperforming salicylate (–7.7 kcal/mol). Conclusion: These findings support the traditional use of C. molle and highlight combrebisbibenzyl A (1) as a promising natural antioxidant with multi-mechanistic potential.
Introduction: Atypical hemolytic uremic syndrome (aHUS) is a potentially life-threatening condition associated with poor clinical outcomes if not treated adequately. Eculizumab has become the standard of care, whereas ravulizumab, a second-generation, high-affinity complement C5 inhibitor, demonstrates comparable efficacy in improving renal function, hematological markers, and dialysis rates. In addition, ravulizumab offers practical advantages, including a longer dosing interval and immediate, complete, and sustained inhibition of free C5, making it a valuable therapeutic option. Methods: Given the limited real-world experience with ravulizumab, we present a case series of six treatmentnaïve aHUS patients who received ravulizumab as first-line therapy. Results: These cases include one pregnancy-related aHUS, one postpartum case, one related to a urinary tract infection, one associated with hypertension, one with a pneumonia-related trigger, and one kidney transplant patient with a prior verotoxin-producing E. coli infection. Altogether, these cases illustrate the challenges in diagnosing aHUS. The choice to administer ravulizumab as first-line treatment was sometimes made in the presence of a clear clinical suspicion, even when not all minor criteria seemed to confirm the diagnosis. In most patients, renal function improved rapidly after ravulizumab administration, followed by recovery of hematological parameters, which were stable in the longer term. As improvements remained sustained over time, the possibility of discontinuing ravulizumab can be evaluated on a case-by-case basis. Conclusion: These cases highlight the importance of early diagnosis, prompt intervention, and multidisciplinary care in managing aHUS. Ravulizumab as first-line therapy proved effective and well-tolerated, with sustained clinical improvements observed across diverse real-world scenarios.
Introduction: This study aimed to detect the co-occurrence of carbapenem resistance genes along with aminoglycoside-modifying enzyme (AME) genes in clinical Enterobacterales isolates to understand the distribution of multiple resistance genes among clinical isolates. Methods: This prospective study was conducted for six months (November 2024 to April 2025) in the department of microbiology of a tertiary care hospital. A total of 30 blood culture isolates were identified as resistant to both carbapenem and aminoglycoside antibiotics using the automated VITEK 2 compact system. The genes responsible for carbapenem resistance (blaNDM, blaOXA-48, blaKPC, blaIMP, and blaVIM) were detected by multiplex realtime PCR, and the aminoglycoside-modifying enzyme genes [APH(3’)-Ia, APH(2”)-Ib, AAC(3)-IIc, AAC(6’)-Ib, and ANT(3”)-I] were detected by the conventional polymerase chain reaction method. All the clinical data, patient demographics, and molecular findings were entered in an MS Excel spreadsheet version 14.0.4734.1000 and analyzed using GraphPad/PRISM software version 10.5.0. Results: Of the 30 Enterobacterales isolates, Klebsiella pneumoniae was the most common isolate (66.7%). Molecular detection revealed blaNDM in 40% isolates and blaOXA48 in 10% isolates. The majority of the AME genes were in combination. The most common combination of the AME gene was AAC(6’)-Ib+ AAC(3)-IIc+ ANT(3”)-I + APH(3’)-I detected in 4 (13.3%) isolates. The most common combination of carbapenem and aminoglycoside resistant genes was blaNDM + blaOXA48 + AAC(6’)-Ib+ AAC(3)-IIc+ ANT(3”)-I+ APH(3’)-I (13.3%). The blaOXA-48 gene had a statistically significant association with AAC(6’)-Ib, ANT(3”)-I, and APH(3’)-I (p <0.05). Conclusion: The Co-occurence of carbapenem resistance and aminoglycoside-modifying enzyme genes in clinical Enterobacterales isolates limits the therapeutic option.
Introduction: Bushenhuoxue formula is a traditional Chinese medicine formula with relatively safe clinical effects, but its mechanism in recurrent spontaneous abortion (RSA) is still unclear. Our present study used Network pharmacology an experimental validation to discuss how Bushenhuoxue formula improves prethrombotic state in RSA. Materials and methods: The active ingredients of Bushenhuoxue formula (Drug) were acquired from our previous study. The putative targets of ZYP relevant to AS were obtained from TCMSP, Swiss Target Prediction, STITCH, DisGeNET, and Gene Cards databases. Protein-protein interactions (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted using the Cytoscape software. Furthermore, in vivo experiments were carried out for target validation in BALB/c mice, collecting placental tissue from different groups, the cell apoptosis by TUNEL assay; the pathology by HE staining; relative mRNA expression by qRT-PCR assay; relative protein expression by IHC and WB assay. Results: Animal experiments, compared with the NC group, the AT-III, PROG, HCG, APC and t-PA concentrations were significantly depressed (P˂0.05, respectively), Apoptosis cell numbers were significantly up-regulated with PI3K/AKT/HIF-1α VEGF significantly depressing (P˂0.001, respectively). With Bushenhuoxue formula supplement, AT-III, PROG, HCG, APC and t-PA concentrations were significantly improved in RSA model mice; and improved pathological changes and apoptosis cell number in placenta tissues (P˂0.05, respectively). However, with LY294002 supplement, the drug treatment effects were disappeared. Conclusion: Bushenhuoxue formula improves prethrombotic state in RSA via stimulating PI3K/AKT/HIF-1α/VEGF pathway in vivo.
Introduction: Diabetes mellitus (DM), particularly type 2 DM (T2DM), is a chronic metabolic disorder requiring novel therapeutic approaches as the available therapies are not meeting the current challenges. This study investigates the anti-diabetic potential of Vigna unguiculata using a network pharmacology approach, supported by in vitro and in silico analyses. Methods: The plant was collected from Khyber Pakhtunkhwa, Pakistan, and subjected to hydroalcoholic extraction and fractionation. In vitro assays included α-amylase, α-glucosidase, and aldose reductase. Target prediction using STITCH and SwissTargetPrediction identified 88 common genes linked to T2DM. Protein-protein interaction (PPI) network analysis highlighted key genes like EGFR, PTGS2, and TLR4 as central nodes in diabetes-related pathways. Molecular docking was used to study the binding affinities of compounds. Results: IC50 values were determined using IBM SPSS Statistics 21 software. The data underwent analysis using one-way ANOVA followed by Dunnett’s multiple comparison test. Significance value was determined at *p < 0.05, **p < 0.01 and ***p < 0.001. In-vitro assays demonstrated significant α-amylase, α-glucosidase, and aldose reductase inhibitory activities. Phytochemical screening identified several bioactive compounds. Functional annotation and KEGG pathway analysis confirmed these genes’ roles in crucial metabolic pathways. Virtual screening revealed strong binding affinities of compounds like Stigmasterol, Luteoline, and Quercetin with GSK3B, PTGS2, and TLR4. The Molecular Dynamics (MD) simulation, binding free energy calculations (MM-PBSA and MM-GBSA), confirmed the results of Virtual screening. Conclusion: In short, these findings underscore V. unguiculata as a promising source for anti-diabetic agents, supporting further clinical trials for T2DM management.
Introduction: Keloid scars are a kind of skin disorder in which the scar grows beyond the boundaries of the original wound. Baicalein, a flavonoid, may treat keloids by targeting fibrosis, inflammation, and possible viral factors. Methods: In silico studies were conducted to evaluate the potential anti-keloid effects of baicalein by predicting its interactions with three key proteins of the transforming growth factor-β (TGF-β) family (PDB IDs: 1VJY, 3TZM, and 7DV6). POM analysis was also used to understand the conditions that could enhance baicalein’s efficacy. Results: The results indicated that baicalein binds effectively to TGF-β family proteins via hydrogen bonds, showing strong affinities (1VJY: -9.9 kcal/mol, 3TZM and 7DV6: -9.3 kcal/mol), indicating its potential as a TGF-β receptor ligand. Osiris analysis gave a drug score of 75% for baicalein, while Molinspiration indicated good bioavailability with a cLogP of 2.84. Atomic charge distribution and pharmacophore site mapping through POM analysis indicate that baicalein exhibits an antiviral pharmacophoric moiety akin to known antiviral agents. This indicates that baicalein may act as a pro-drug, undergoing metabolic transformation to form a bis-bidentate ligand. Such ligands are crucial for forming bimetallic complexes that can function as efficient biocatalysts against various biological targets. Conclusion: In-silico analysis suggests that baicalein may influence TGF-β receptors and exhibit anti-keloid activity. Additionally, POM analysis recommends that baicalein may serve as a lead compound with the potential to modulate TGF-β signalling and exhibit antiviral properties, indicating it as a dual-action agent against keloids and viral infections.
Introduction: Wound management presents significant challenges, requiring effective treatments. Herbal extracts have been traditionally used to support healing due to their anti-inflammatory, antimicrobial, and cellregenerative properties. Methods: This study aimed to evaluate the therapeutic efficacy of Pau D’Arco (Tabebuia), Yarrow (Achillea millefolium), Gotu Kola (Centella asiatica), Figwort (Scrophularia nodosa), and Broadleaf (Plantago major) extracts, both individually and combined, on wound healing in vitro and in vivo in equine models. In vitro tests using human macrophages and keratinocyte cell lines to assess cellular responses such as cytokine secretion and phagocytic activity under simulated inflammatory conditions. Additionally, pilot case studies on equines with open wounds provided practical insights into the extracts’ healing capabilities. Results: MTT assay was used to assess cytotoxicity. The extracts did not significantly affect the viability of HaCaT or THP-1 cells. The herbal extracts reduced IL-8 levels and increased phagocytic activity in macrophages, indicating an ability to modulate inflammatory responses. In vivo, the extracts were well tolerated and associated with supported healing in equines. These effects were suggested to be attributed to the synergistic actions of the herbal components. Conclusion: These findings suggest that the herbal extracts may be useful for supporting wound healing. Their natural anti-inflammatory and healing properties could provide an additional option alongside traditional wound management approaches.
Introduction: The current scenario of tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) has presented an almost insurmountable challenge to hospitals with high patient numbers. Delayed diagnosis of TB is a major hurdle in preventing the employment of efficient therapeutics, leading to the development of drug resistance. Hence, an easily accessible diagnostic method, particularly for resource for resource-limited settings, is pertinent for the rapid identification of MTB-infected patients. In pursuit of developing such an assay, the present study offers a CLAP-TB (CRISPR-Cas coupled RT-LAMP Amplification Protocol for Tuberculosis) assay, which will allow us to diagnose TB rapidly and visually. Methods and results: Herein, the visual MTB detection consists of a method utilizing 232 different samples (spu tum, urine, serum) from 82 patients for reverse transcription loop-mediated isothermal amplification (RT-LAMP). Additionally, the assay also utilizes the integration of a CRISPR-Cas12-based system using different guide RNAs of IS6110 and an internal control POP7 (human RNase P) genes along with visual detection via lateral flow readout based dipsticks with the unaided eye (~134 min). Overall, the limit of detection for CLAP-TB assay was up to 1 ag of RNA, while the clinical sensitivity and specificity were 98.27% and 100%, respectively, on the pilot scale. Conclusion: Together, our CLAP-TB assay offers proof of concept for a rapid, sensitive, and specific method with the minimum technical expertise required for TB diagnosis in developing and resource-limited settings.
Introduction: Adequate hyperglycemic control is still a huge challenge with the clinically used therapeutics. New, more effective anti-diabetic agents are on the top list of drug discovery projects. Methods: This article deals with the in vitro anti-diabetic potential of 2, 3 dichloroIndolinone (C1) and 2, 6-dichloroIndolinone (C2) on α-glucosidase and α-amylase followed by in silico analysis. Results: Both compounds, C-1 and C-2, caused significant inhibition of α-glucosidase at various test concentrations with IC50 of 35.266 μM and 38. 379 μM, respectively. Similarly, compounds C-1 and C-2 elicited significant anti-α-amylase action with IC50 values of 42.449 μM and 46.708 μM, respectively. The molecular docking investigation regarding the α-glucosidase and α-amylase binding site was implemented to attain better comprehension with respect to the pattern in which binding mechanics occur between the C1 and C2 molecules and the active sites, which illustrated a higher binding efficacy in appraisal with reference inhibitor and acarbose. The interactions between the active compounds C1 and C2 with the active site residues were mainly polar bonds, hydrogen bonding, π−π, and π−H interactions, which contributed to a strong alignment with the enzyme backbone. Similarly, effective binding is frequently indicated by a strong and stable hydrogen-bonding pattern, which is suggested by the minimal fluctuation in MM-PBSA values. Conclusion: In short, this study will contribute to providing these compounds with an improved anti-diabetic profile and decreased toxicity.
Introduction: Candida albicans biofilm formation contributes significantly to antifungal resistance, necessitating new treatment strategies. Annona muricata Lin., a traditional herbal remedy, has shown promise in combating microbial infections. This study evaluated the antibiofilm activity of the methanol extract of A. muricata leaves, alone or combined with fluconazole, against C. albicans. Methods: Phytochemicals in the methanol extract were analyzed using LC-MS, biofilm metabolic activity was assessed with the XTT assay, and morphological changes were examined via scanning electron microscopy (SEM). Molecular docking evaluated the binding of compounds in the A. muricata extract to the Sap3 receptor (PDB: 2H6T). Results: LC-MS identified 17 phytochemicals in the methanol extract. The extract showed dose-dependent inhibition of biofilm formation, reaching ~60% inhibition at 240 μg/ml. Fluconazole inhibition increased from 32% to 76% as concentrations rose from 15 to 240 μg/ml. The combination of A. muricata and fluconazole enhanced inhibition, ranging from 74% to 78% at 15–240 μg/ml. SEM analysis revealed altered biofilm morphology and loss of cell integrity with the combination treatment. Phytochemicals showed high binding affinity (−9.7 to −8.0 kcal/mol) for the Sap3 enzyme, suggesting therapeutic potential. Conclusion: These findings suggest that compounds in the A. muricata methanol extract synergize with fluconazole at sub-inhibitory concentrations to suppress C. albicans biofilm formation. This paves the way for antifungal treatments that may mitigate fluconazole resistance using this plant extract.
Background: Withania somnifera is among the most widely prescribed medicinal plants in traditional Indian medicine. Hydroalcoholic extract of the roots of this plant was investigated for its effects on the overall health and lifespan of the model worm Caenorhabditis elegans. Methods: The extract’s effect on worm lifespan and fertility was observed microscopically. Worm motility was quantified through an automated worm tracker. The metabolic activity of the worms was captured using the Alamar Blue® assay. Differential gene expression in extract-treated worms was revealed through a whole transcriptome approach. Results: Extract-exposed gnotobiotic worms, in the absence of any bacterial food, registered longer lifespan, higher fertility, better motility, and metabolic activity. Whole transcriptome analysis of the extract-treated worms revealed the differential expression of the genes associated with lifespan extension, eggshell assembly and integrity, progeny formation, yolk lipoproteins, collagen synthesis, cuticle molting, etc. This extract seems to exert its beneficial effect on C. elegans partly by triggering the remodeling of the developmentally programmed apical extracellular matrix (aECM). Differential expression of certain important genes (cpg-2, cpg-3, sqt-1, dpy-4, dpy-13, and col-17) was confirmed through PCR assay too. Some of the differently expressed genes (gfat-2, unc-68, dpy-4, dpy-13, col-109, col-169, and rmd-1) in worms experiencing pro-health effect of the extract were found through co-occurrence analysis to have their homologous counterpart in humans. Conclusions: Our results validate the suitability of W. somnifera extract as a nutraceutical for healthy aging.
Objectives: To assess through an indirect treatment comparison (ITC) the potential benefit of faricimab over the anti-vascular endothelial growth factor (VEGF) real-life scenario, hereby defined standard of care (SoC), in Italy, that is, aflibercept, bevacizumab, and ranibizumab, in patients with neovascular age-related macular degeneration (nAMD) naïve to any anti-VEGF treatment. Methods: Individual patient-level data from the phase III clinical trials TENAYA and LUCERNE (faricimab cohort) and the real-world study RADIANCE (RADIANCE cohort) were used. Efficacy was evaluated with changes in best corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to 1 year (week 52 in the RADIANCE and week 48 in the faricimab cohorts, respectively). Propensity score-based inverse probability of treatment weighting was utilized to balance cohorts and mitigate bias due to potential confounding. Sensitivity analyses were performed to evaluate treatment differences adjusted for the number of injections. Results: The ITC included 513 patients treated with faricimab and 263 patients treated with SoC. At 1 year, faricimab showed a greater mean BCVA gain (treatment difference +5.4 letters, p<0.001) and CST reduction (treatment difference −71.8 μm, p<0.001) compared to SoC. Sensitivity analyses confirmed the robustness of results, showing a BCVA improvement of +4.0 letters and a CST reduction of −71.5 μm in favor of faricimab. Conclusions: Despite the limitations due to the use of ITC and the comparison between clinical trials and real-world cohorts, the present analysis suggests potential benefits in terms of vision gain and CST reduction in naïve nAMD patients treated with faricimab compared with SoC in a real-world setting.
Introduction: Colorectal cancer incidences continue to increase annually, worldwide. Herbal plants with antiproliferative properties received research interest as agents that can be adjuvant therapies with chemotherapy drugs to enhance their efficacy and reverse drug resistance. Methods: Sclerocarya birrea ethanolic (SBE) and aqueous (SBW) extracts combined with doxorubicin (DOX) against drug-sensitive and drug-resistant colorectal cancer cells were investigated for their potential adjuvant and drug resistance reversal. The extracts were assessed for their potential anticancer activities on HCT15 and HT29 cell lines as well as their doxorubicin potentiating and drug resistance reversal effects respectively. The extracts were assessed for their cytotoxicity on normal 3T3-L1 fibroblast cells. Results: Both SBE and SBW extracts exhibited no toxicity against normal 3T3 cells and showed low activity on the HT29 cell line. Contrarily, resistant HCT15 cells showed moderate to low activity with significantly higher inhibitory concentration (IC)50 values. The combination of SBE with DOX and SBW with DOX resulted in antagonistic interactions, causing an increase in IC50 values for HT29 and HCT15 cells. In contrast, the combination of DOX and verapamil (VER) produced an additive effect, with no change in their IC50 values. Conclusion: Based on the findings from the combination treatment, the SBE and SBW extracts demonstrated higher efficacy and synergistic effects combined with DOX at IC75 compared to the combination of DOX and VER, suggesting their potential as anticancer agents. However, further research on both the SBE and SBW extracts’ mechanisms of action and in vivo effects is warranted.
Background: Edible fruits and resins provide various benefits to mankind including potential medicinal applications. This study aimed to determine the cytotoxicity, selectivity, and clonogenicity of fruits and exudates of certain Saudi medicinal plants (Anethum graveolens (BEP-09), Opuntia ficus-indica (L.) Miller (BEP-10), Boswellia serrata Roxb. ex Colebr. (BEP-11), and Commiphora myrrha (BEP-12)) against human liver adenocarcinoma (HepG2). Methods: Initial cytotoxicity and cell line selectivity against different cell lines were screened using MTT assay. The most promising extract was subjected to gas chromatography-mass spectrometry (GC-MS) analysis to determine the main phytoconstituents. Clonogenicity was checked for the most active extract. Results: The selected plants’ fruits and resins possess a significant cytotoxic activity estimated as IC50. The fruit of BEP-10 was found to be the most active extract against liver cancer cells (IC50 = 2.82) comparable to both doxorubicin (IC50 = 1.40) and camptothecin (IC50 = 1.11). It showed a selectivity index of 4.47 compared to the normal human foetal lung fibroblast (MRC5) cells. BEP-10 showed a dose-dependent clonogenic effect against HepG2 cells comparable to the effect of doxorubicin. The GC-MS chromatogram of BEP-10 extract revealed the presence of eight small polar molecules, representing 73% of the total identified compounds and the rest three molecules (27%) were non-polar constituents. The furan derivatives represent the chief components in BEP-10 (16.3%), while the aldehyde 5-(hydroxymethyl)-2-furancarboxaldehyde was found to be the main molecule (13.2%). Conclusion: The fruits of BEP-10 have a potential cytotoxic effect particularly against HepG2. The identified phytoconstituents in the tested plant extract might contribute to the investigated cytotoxic activity.
Background: Levofloxacin, a fluoroquinolone, is an extensively used antibiotic effective against both positively and negatively staining bacteria. It works by inhibiting bacterial topoisomerase type II and topoisomerase type IV, resulting in impaired DNA synthesis and bacterial cell death. Eryptosis is another term for apoptotic cell death of erythrocyte marked by cell shrinkage, phosphatidylserine (PS) flipping, and membrane blebbing. Methods: The intent of the present research was to look at the eryptotic effect of levofloxacin by exposing erythrocytes to therapeutical doses (7, 14 µM) of levofloxacin for 48 hours. Cell size evaluation, PS subjection to outside, and calcium channel inhibition were carried out to investigate eryptosis. Oxidative stress generated by levofloxacin was measured as a putative mechanism of eryptosis using glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase activities. Similarly, hemolysis measurements demonstrated levofloxacin’s cytotoxic effect. Results: Our findings showed that therapeutic doses of levofloxacin can cause a considerable decline in antioxidant enzymes activities, as well as induce cell shrinkage, PS externalization, and hemolysis in erythrocytes. The role of calcium in triggering erythrocyte shrinkage was also confirmed. Conclusion: In conclusion, our findings showed that the indicated levofloxacin doses caused oxidative stress, which leads to erythrocyte death via eryptosis and hemolysis. These findings emphasize the importance of using levofloxacin with caution and the need for additional research to mitigate these side effects.
