Introduction: Persistent microbial biofilms and complex root canal anatomy continue to challenge effective endodontic disinfection. This systematic review aimed to evaluate the antimicrobial, antibiofilm, anti-inflammatory, and regenerative effects of propolis nanoparticles (PNPs) in endodontic applications. Methods: A comprehensive search of Web of Science, PubMed, Scopus, EMBASE, and the Cochrane Library was conducted from database inception to April 2026 according to PRISMA guidelines. In vitro, animal, and clinical studies evaluating PNP-based delivery systems in endodontics were included. Risk of bias and methodological quality were assessed using Quality Assessment Tool for In Vitro Studies (QUIN), SYRCLE, and RoB 2 tools. Results: Fifteen studies met the inclusion criteria, most of which were in vitro investigations. PNP-based systems demonstrated antimicrobial and antibiofilm activity, particularly against Enterococcus faecalis. Several studies also reported reduced inflammation, improved dentinal tubule penetration, sustained bioactive release, and favorable biocompatibility compared with conventional materials and pure propolis formulations. Conclusion: PNPs show promising potential as adjunctive endodontic therapeutic agents due to their antimicrobial and biocompatible properties. However, current evidence is limited by the predominance of heterogeneous preclinical studies; well-designed clinical studies are required to confirm their efficacy and safety.
Introduction: Hedysarum alpinum L. (HA) contains considerable amounts of polyphenols and saponins, and exhibits immune-enhancing and antiviral properties. Evidence indicates that triterpenoid saponins possess neuroprotective effects against neurodegenerative damage. The present study evaluated the effect of an HA saponin-rich n-butanol fraction (HABF) on cognitive deficits induced by scopolamine in a rat model. Methods: Cognitive impairment was assessed using passive avoidance (PA) and novel object recognition (NOR) tasks. Total triterpene saponins of HABF were quantified by the colorimetric method using oleanolic acid as a standard compound. Biochemical analyses of hippocampus tissue included measurements of acetylcholinesterase (AChE) activity, choline acetyltransferase (ChAT), catalase (CAT), and tumor necrosis factor-α (TNF-α). Results: HABF contained 131 ± 0.02 mg oleanolic acid equivalent (OAE)/g of total triterpene saponins. Scopolamine significantly impaired memory, as shown by a decreased discrimination index in the NOR test and reduced retention latency in the PA test. Pretreatment with HABF (40 and 80 mg/kg) significantly alleviated the memory deficits in both tasks. Scopolamine significantly increased AChE activity and TNF-α levels, and decreased CAT activity compared to the vehicle-treated group. These alterations were significantly reversed by HABF treatment, whereas ChAT activity remained unchanged compared with the MPTP-treated group. Conclusion: HABF, rich in triterpene saponins, ameliorates scopolamine-induced memory impairment, likely through the inhibition of AChE activity and modulation of oxidative stress and inflammation. These findings may suggest its potential neuroprotective effect in cognitive dysfunction.
Oxidative stress and antioxidant systems are complex components of human physiology and pathology. Reactive oxygen species (ROS), previously viewed as undesirable byproducts of cellular metabolism, have now been identified as critical signaling agents that participate in cell proliferation, differentiation, and immune responses. Both endogenous and exogenous antioxidants play a critical role in redox homeostasis by countering surplus ROS and preventing oxidative injury. Nevertheless, growing evidence points to the paradoxical dual nature of antioxidants, casting doubt on their universally positive effects. This paradox is particularly pronounced in cancer. Although high levels of ROS promote tumor development and progression by causing genomic instability and activating oncogenic signaling, high levels of ROS can also cause cancer cell death and represent a major mechanism of action of anticancer therapies. Tumor cells respond by increasing their antioxidant capacity, which enables them to maintain ROS at levels that promote survival without causing cytotoxicity. Exogenous antioxidant supplementation can therefore disrupt this balance, potentially stimulating tumor growth, enabling metastasis, and diminishing the efficacy of ROS-dependent therapies like chemotherapy and radiotherapy. Moreover, plant-derived antioxidants, such as polyphenols and flavonoids, exhibit both antioxidant and pro-oxidant effects, highlighting the context-specificity of redox modulation in cancer. Although these compounds may have chemopreventive advantages, their impact on established malignancies is complex and requires additional research. This review provides a broad description of the duality of oxidative stress and antioxidants, specifically regarding their implications in cancer treatment and resistance. A better comprehension of redox biology is needed to develop more effective and personalized therapeutic interventions based on the specific regulation of oxidative stress.
Introduction: Inflammation plays a central role in various chronic diseases. Flavonoids are widely recognized for their pharmacological potential, including anti-inflammatory properties. This study aimed to isolate O-methylated flavonols from Alpinia monopleura and to predict their potential anti-inflammatory activity using computational approaches. Methods: Rhizomes of A. monopleura were extracted with methanol, partitioned, and fractionated by vacuum liquid chromatography (VLC). Isolated compounds were characterized by 1H- and 13C-NMR spectroscopy. The anti-inflammatory potential was evaluated by molecular docking against multiple inflammation-related targets using AutoDock Vina, with native ligands as references, followed by in silico pharmacokinetic and toxicity predictions using pkCSM and ProTox 3.0. Results: Two O-methylated flavonols, kaempferol 3,7,4′-trimethyl ether (2a) and quercetin 3,7,4′-trimethyl ether (2b), were isolated from the ethyl acetate fraction of A. monopleura. Both compounds exhibited favorable binding energies toward multiple inflammatory targets. Compounds 2a and 2b showed stronger binding than native ligands against inducible nitric oxide synthase (iNOS), lipoxygenase (LOX), and mPGES-1, and interacted with COX-2, IKK, JAK2, and NOX5, which are key proteins regulating inflammatory signaling pathways, with binding energies generally below −8.0 kcal/mol. Predicted pharmacokinetic profiles indicated good intestinal absorption and membrane permeability, with acceptable toxicity, with binding energies generally below −8.0 kcal/mol. Predicted pharmacokinetic profiles indicated good intestinal absorption and membrane permeability, with acceptable toxicity. Conclusion: O-methylated flavonols from A. monopleura showed potential as multi-target anti-inflammatory leads based on in silico analyses. These findings provide a scientific basis for further experimental studies and support the exploration of A. monopleura–derived flavonols as candidate compounds for the development of safer anti-inflammatory agents. Future in vitro and in vivo studies are warranted to validate their pharmacological efficacy and relevance to clinical practice.
Introduction: Eugenol, a natural phenolic compound obtained from clove and cinnamon, has been reported to show anticancer properties in breast cancer models. Metabolic reprogramming is a hallmark of breast cancer and can be regulated by AMPK. The PRKAA1 gene encodes the catalytic subunit of AMPKα1. This study aimed to investigate the effects of eugenol on cell viability and PRKAA1 expression in human breast cancer cell lines. PRKAA1 expression patterns and prognostic relevance in breast cancer patient datasets were also analyzed. Methods: RNA-seq data from ENCORI/StarBase were employed to compare PRKAA1 expression in tumor and normal breast tissues. Kaplan–Meier analysis evaluated possible associations between PRKAA1 expression levels and overall survival. MCF-7 and MDA-MB-231 cell lines were treated with eugenol, and cell viability was assessed using the MTT assay. PRKAA1 expression levels were measured by RT-qPCR after eugenol treatment and compared with controls. Results: Bioinformatics analysis showed lower PRKAA1 expression in breast cancer compared with normal breast samples (P = 4.3e-24, false discovery rate [FDR] = 4.4e-23). Survival analysis showed no significant association between PRKAA1 expression and overall survival in breast cancer patients (P = 0.69; hazard ratio [HR] = 1.07). Eugenol reduced the viability of both cell lines and showed greater toxicity with increasing concentrations and exposure time. Eugenol treatment downregulated PRKAA1 expression (P < 0.001). Conclusion: Eugenol treatment altered PRKAA1 expression in both cell lines. These findings may suggest a potential link between eugenol induced cytotoxicity and changes in energy homeostasis genes; however, further studies are required to clarify the role of AMPK signaling in this context.
Introduction: Soybean-derived peptides have emerged as promising therapeutic agents in oncology due to their bioactivity, low toxicity, and biocompatibility. This study aimed to conduct a comparative analysis to assess whether soybean-derived anticancer peptides could serve as therapeutic agents in hepatocellular carcinoma (HCC). Methods: The peptide structures were predicted using UCSF ChimeraX, while the preparation of target proteins and peptides was performed using BIOVIA Discovery Studio Visualizer. The interactions between the peptides and the SALL4-NuRD, VEGF, and GPC3 proteins were analyzed through molecular docking studies. Results: Docking results revealed that the peptide WMLPSYSPY exhibited superior binding affinity (-237.813) compared to other peptides. Alanine scanning assays demonstrated that residues Tyr6 and Tyr9 played crucial roles in peptide interactions with SALL4-NuRD and VEGF, while Trp1 and Tyr6 were crucial for peptide interaction with GPC3. Conclusion: Predictive characteristics of the WMLPSYSPY peptide suggest its potential as a therapeutic agent for HCC, albeit with low stability and uptake. Further in vitro and in vivo studies are warranted, alongside structural modifications to enhance its pharmacological properties.
Introduction: This study evaluated the traditional uses of Tamarix dioica stem bark extracts, with emphasis on antioxidant, anti-inflammatory, antimicrobial, antidiarrheal, and antipyretic activities, using both laboratory- and animal-based experimental approaches, to evaluate its traditional uses. Methods: The methanolic and n-hexane extracts of T. dioica stem bark were analyzed for phytochemical constituents, total phenolic and flavonoid content, and antioxidant activity. Radical scavenging capacity was determined through DPPH and nitric oxide assays using ascorbic acid as a reference standard. Additional evaluations included antimicrobial screening, thrombolytic and membrane stabilization assays, and cytotoxic assessment. Biological activities, including analgesic, antidiarrheal, and antipyretic effects, were examined in Swiss albino male mice at oral doses of 200 and 400 mg/kg body weight. Results: Among the tested extracts, the methanolic fraction demonstrated stronger antioxidant performance than the n-hexane fraction, producing lower IC₅₀ values in both DPPH and nitric oxide scavenging assays (28.91 ± 0.64 µg/mL and 26.24 ± 0.58 µg/mL, respectively). Antimicrobial testing revealed mild inhibitory effects, with the n-hexane fraction producing inhibition zones up to 8 mm against selected bacterial strains and 7 mm against Candida albicans. Both extracts reduced diarrheal frequency, achieved 70.27% inhibition at the higher dose. Pronounced analgesic and antipyretic responses were observed in the n-hexane extract-treated groups, with maximal writhing suppression of 78.43% (P < 0.001) and temperature reduction of 4.4 % (P < 0.001). Conclusion: Stem bark extracts of T. dioica exhibited multiple pharmacological activities, particularly antioxidant, antimicrobial, analgesic, and antidiarrheal effects, confirming its traditional uses. These findings support continued investigation into the isolation and characterization of the active phytochemicals responsible for the observed responses.
Introduction: Melia dubia seeds are traditionally used against diabetes mellitus and cancer. Molecular docking studies were performed to evaluate the binding affinity of major compounds against α-glucosidase and the mechanistic target of rapamycin (mTOR), a key regulator of cell growth and proliferation. Methods: Phytoconstituents of the alcoholic seed extract were analyzed using network pharmacology to identify key molecular targets along with signaling pathways involved in diabetes and cancer. Molecular docking studies were performed to identify the binding affinity for major compounds against α-glucosidase and mTOR, which regulates cell division and proliferation. In vitro antidiabetic activity was assessed using an α-glucosidase inhibition assay, while anticancer activity was evaluated through a cytotoxicity assay using the MTT method. Results: Network pharmacology analysis revealed that the phytoconstituents modulate critical pathways, consisting of phosphoinositide 3-kinase–Akt, adenosine monophosphate-activated protein kinase, nuclear factor kappa-B, vascular endothelial growth factor, and insulin signaling pathways. Molecular docking demonstrated strong binding affinities of compounds such as 2-phenylanthraquinone, 2,2-dimethylpropyl, and quebrachamine with α-glucosidase and the mTOR. The extract exhibited significant α-glucosidase inhibition with an IC₅₀ value of 33.59 µg/mL, against 28.11 µg/mL for Acarbose. A cytotoxicity assay showed dose-dependent cancer cell inhibition with an IC₅₀ of 31.82 µg/mL, compared to 20.41 µg/mL for cisplatin. Conclusion: The findings may support the dual antidiabetic and anticancer potential of the alcoholic extract of M. dubia seeds. The integrated in silico and in vitro results suggest a promising natural therapeutic candidate requiring further validation.
Insulin resistance is a significant metabolic dysfunction that contributes to the pathogenesis of type 2 diabetes mellitus (T2DM). As interest grows in functional foods for chronic disease management, seeds of various plants, such as Linum usitatissimum (flaxseed), Salvia hispanica (chia), Cucurbita pepo (pumpkin), Cannabis sativa (hemp), and Sesamum indicum (Sesame) have gained prominence due to their rich profile of bioactive compounds. These seeds contain polyunsaturated fatty acids (PUFAs), dietary fibre, lignans, polyphenols, and key micronutrients that act synergistically to enhance insulin sensitivity. The mechanisms by which these components exert their effects include modulation of insulin signaling pathways, activation of AMP-activated protein kinase (AMPK), enhancement of adiponectin secretion, and improvement of gut microbiota composition. For instance, chia and pumpkin seed extracts have shown reductions in serum glucose and hemoglobin A1C (HbA1c) in diabetic rodent models. Though little evidence from both animal and human studies suggests that some seed extracts and oils can lower blood glucose, reduce insulin resistance, and improve lipid profiles. This review summarises the mechanistic insights, preclinical and clinical evidence, and functional food applications of these seeds, while highlighting current research gaps. Incorporating functional seeds into dietary interventions may offer a sustainable and accessible approach for managing insulin resistance and preventing T2DM. Despite promising findings, more robust and long-term human clinical trials are required to validate these effects and establish standardized dosages.
Introduction: Drug resistance has heightened the demand for natural antiviral agents. Thymoquinone (TQ), a major bioactive component of black seed oil, has demonstrated antiviral activity in numerous studies. However, its potential efficacy against herpes simplex virus type 1 (HSV-1) has not been extensively explored. This research aimed to assess the in vitro antiviral effect of TQ and its synergistic relationship with acyclovir against HSV-1. Methods: In this experimental study, the cytotoxic effects of TQ and acyclovir on Vero cells were evaluated using the MTT test. The antiviral activity of TQ and acyclovir with sub-cytotoxic doses and combinations with TQ (CC10) on HSV-1 virus replication was investigated using both MTT and 50% tissue culture infectious dose (TCID50) assays. Compusyn software was used to analyze the combination index (CI) of TQ and acyclovir. Results: The 50% cytotoxic concentration (CC50) values of acyclovir and TQ were calculated to be 537.7 and 57.5 μM, respectively. The 50% inhibitory concentration (IC50) values of acyclovir, TQ, and acyclovir together with 10 μM TQ (CC10) were obtained to be 0.25, 13.38, and 0.04 μM, respectively. Based on the TCID50 findings, both drugs, whether used separately or in combination, significantly diminished viral titers. Synergistic effects were identified at most concentrations, with the strongest synergy observed at 0.3 μM TQ in combination with 0.03 μM acyclovir. Conclusion: TQ possesses potent antiviral activity against HSV-1 virus and has synergistic effects with acyclovir to inhibit virus replication. Further studies need to be carried out to assess its utility and safety profile.
Introduction: Staphylococcus aureus is a pathogenic bacterium commonly present in chronic wounds and can contribute to clinical complications, particularly among diabetic patients. Quercetin is a natural flavonoid with outstanding antioxidant and antibacterial properties. This study aimed to elucidate the molecular mechanisms of quercetin in modulating S. aureus-infected wound healing, particularly by identifying key target genes, in silico molecular docking verification, and investigating its in vitro antibacterial properties. Methods: A bioinformatics investigation was conducted to identify interrelated genes, using a Venn diagram and protein–protein interaction (PPI) analysis. Hub genes were identified using the Maximal clique centrality (MCC) and Density of maximum neighbourhood component (DMNC) algorithms. Molecular docking assessed interactions between quercetin and key targets (TP53 and CYP3A4), followed by in vitro validation of quercetin’s antibacterial activity against S. aureus. Results: Protein-protein interaction (PPI) and Gene Ontology (GO) analyses showed that quercetin regulates the genes involved in apoptosis (TP53, MCL1), oxidative stress (CYP3A4, CYP2E1), and the insulin-related pathway (INS, SLC2A2, HNF1A). TP53, INS, and CYP3A4 exhibited the highest DMNC and MCC scores. Quercetin bound to CYP3A4 (–6.74 kcal/mol) and TP53 (–5.89 kcal/mol), and stabilized by multiple hydrogen and hydrophobic interactions. In vitro antibacterial assays confirmed that quercetin inhibited S. aureus growth in a dose-dependent manner with MIC and IC50 values of 62.5 and 111.23 µg/mL, respectively. Conclusion: The integrated gene network and molecular interaction approach highlight quercetin’s potential as a bioactive compound for accelerating healing in infected and diabetic wounds.
Introduction: Acacia tortilis ssp. raddiana is rich in bioactive phytochemicals, particularly phenolic constituents, exhibiting antioxidant and anti-inflammatory activities. Therefore, this study investigated the phytochemical composition and analgesic, anti-inflammatory, and anti-fibrotic effects of Acacia raddiana. Methods: The antinociceptive and anti-inflammatory effects of the hydroethanolic leaf extract (0.5–1 g/kg) were evaluated in Swiss albino mice using the models of thermal nociception, chemical nociception, and carrageenan-induced paw inflammation. The early therapeutic effects of the leaf extract and gum solution were assessed in an experimental pulmonary fibrosis model induced by bleomycin. The phytochemical composition was investigated using standard qualitative and quantitative methods based on precipitation and colorimetric reactions. Moreover, the leaf extract was analyzed by high-performance liquid chromatography (HPLC) to identify phenolic compounds. Results: Phytochemical screening revealed flavonoids, saponins, tannins, anthraquinones, coumarins, steroids, and triterpenes in the leaf extract, and saponins, terpenes, sterols, and coumarins in the gum. The polysaccharide content of the gum was estimated at 58.8% (w/w). HPLC analysis showed that rutin was the major constituent of the leaf extract (24%). Pretreatment with the extract (0.5–1 g/kg, p.o.)significantly reduced acetic acid–evoked writhing, carrageenan-mediated paw swelling, and increased reaction latency in the hot plate test (P<0.01). Both the extract and gum attenuated weight loss, oxidative damage, pulmonary collagen accumulation, and inflammatory alterations associated with bleomycin-mediated lung injury. Conclusion: These results may support the therapeutic potential of A. tortilis ssp. raddiana in pain, inflammation, and pulmonary fibrosis.
Introduction: Marchantia paleacea contains macrocyclic bisbibenzyls, including marchantins with known cytotoxic, antioxidant, and antimicrobial activities, with no known mechanism of action. This study aimed to evaluate the cytotoxic potential of three solvent extracts—70% ethanol (EEMP), ethyl acetate (EAEMP), and n-hexane (NHEMP)—of M. paleacea and to assess molecular interactions of their bioactive compounds through in silico simulations against cancer-related proteins. Methods: Cytotoxicity was determined on MCF-7 and T47D breast cancer cell lines using the MTT assay, with doxorubicin as a positive control. Chemical profiling of the most active extract was performed using Fourier-transform infrared (FTIR) spectroscopy and gas chromatography-mass spectrometry (GC-MS), followed by molecular docking against carbonic anhydrase II (CA-II, PDB ID: 1T47) and cyclin-dependent kinase 2 (CDK2, PDB ID: 1T46). Results: Among the tested extracts, EAEMP showed the strongest cytotoxicity (IC₅₀ = 8.68 µg/mL for MCF-7; 12.78 µg/mL for T47D), compared with EEMP (119.2 and 64.33 µg/mL) and NHEMP (62.07 and 229.8 µg/mL). GC–MS identified Marchantin A, B, and C as major constituents, with Marchantin C exhibiting the highest docking affinity (ΔG = −8.62 kcal/mol) at residues D810 and E640. Conclusion: The ethyl-acetate extract of M. paleacea demonstrates significant in vitro and in silico anticancer potential, suggesting its promise as a semi-polar source of cytotoxic bisbibenzyl compounds for future natural anticancer drug development.
Introduction: Acacia raddiana is a Saharan medicinal plant traditionally used to treat respiratory disorders. This study investigated the protective effects of A. raddiana gum against urethane-induced pulmonary alterations in rats. Methods: Twenty rats were divided into four groups: control, urethane, and urethane plus gum (1 g/kg or 2 g/kg). Urethane was administered at a dose of 0.375 g/kg over 14 weeks, with 3-week intervals between injections (i.p.). The gum was administered daily during the final four weeks of the study. Clinical, macroscopic, histopathological, and oxidative stress parameters were assessed. Results: Urethane caused epistaxis, palpable thoracic and cervical masses, lung tumors, bronchiolar epithelial hyperproliferation, mucin overproduction, and alveolar wall cellular hyperplasia. Urethane also increased catalase (272.7 ± 19.94; P < 0.01) and peroxidase (1.64 ± 0.02; P < 0.0001) activities in lung tissue compared with the control group (124.1 ± 27.28 and 0.12 ± 0.0, respectively). Treatment with A. raddiana gum (1 g/kg) attenuated lung damage, reducing tumor formation, epithelial hyperproliferation, alveolar hyperplasia, and mucin overproduction. It also significantly increased catalase and peroxidase activities compared to the urethane-treated rats (P < 0.05). At 2 g/kg, gum decreased catalase (120.4 ± 14.29; P < 0.01) and peroxidase (0.64 ± 0.02; P < 0.0001) activities compared to the urethane group. At this dose, dark-red lung coloration indicated potential toxicity. Conclusion: This study demonstrates that A. raddiana gum at 1 g/kg protects against urethane-induced pulmonary carcinogenesis in rats by preserving lung structure, reducing mucin overproduction, and modulating oxidative stress.
Introduction: Leishmaniasis is a major global health challenge with limited treatment options and rising drug resistance. Medicinal plants, traditionally used in many regions, offer a promising source of new antileishmanial agents. This study aims to systematically review global in vitro evidence on the antileishmanial activity of medicinal plants. Methods: Data published between 2013 and 2025 were systematically retrieved from four databases: ScienceDirect, Scopus, PubMed, and Web of Science. The search used combinations of the keywords "plant extract," "Leishmania," "medicinal plants," "herbal extract," "traditional medicine," and "herbal medicine." A total of 29 studies met the inclusion criteria, encompassing 271 in vitro experiments. The difference in half-maximal inhibitory concentration (D-IC₅₀) was calculated to compare the efficacy of the tested extracts or compounds relative to the positive control, with negative values indicating stronger inhibitory activity. Results: Seventy-two different plant species were thoroughly tested against Leishmania spp. On the other hand, the heterogeneity study revealed significant variations among studies (I-square greater than 75%). Linear regression analysis demonstrated significant antileishmanial activity for several medicinal plants and their bioactive compounds. Myrtus communis L., Peganum harmala, and Ferula macrecolea showed notable effects, with D-IC₅₀ values of −20.315, −69.650, and −13.200 μg/mL, respectively (P < 0.001). Among the bioactive molecules, terpinolene (−262.570), plumericin (−241.850), and ergosterol peroxide (−240.470) exhibited the strongest inhibitory effects, all highly significant (P < 0.001). Conclusion: This review highlights promising natural compounds with antileishmanial properties that warrant further investigation in upcoming laboratory and clinical studies.
Introduction: The process of wound healing is intricate and includes tissue remodelling, cell proliferation, and inflammation. Elemi essential oil (EEO) from Canarium luzonicum exhibits anti-inflammatory, antibacterial, and antioxidant properties, yet its wound-healing efficacy in vivo remains untested. This study aimed to evaluate the therapeutic potential of EEO in promoting wound healing in rats. Methods: Male Wistar rats were assigned to EEO-treated (10% w/w), reference-treated (1% silver sulfadiazine), and control (soft paraffin) groups (n=6 each). Full-thickness dorsal wounds (2 cm) were created. Wound contraction was monitored on days 1, 4, 8, 12, 16, and 21. Serum interleukin-1-beta (IL-1β), tumour necrosis factor-alpha (TNF-α), and CD68 were measured via enzyme-linked immunosorbent assay (ELISA). Tissue reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) levels were assessed. Histopathology and caspase-3 immunohistochemistry (IHC) were also performed. Results: EEO accelerated wound closure, achieving complete healing by day 16 (P<0.001). IL-1β and TNF-α levels were reduced in EEO-treated rats (658.3 ± 52.3 pg/mg; 333.3±24.72 pg/mg) compared with the control (983.2 ± 60.2 pg/mg; 650 ± 42.82 pg/mg; P<0.001) and reference (841.7 ± 32.7 pg/mg; 466.7 ± 33.3 pg/mg; P<0.01). CD68 decreased significantly (16.8 ± 0.9 ng/dl; P<0.001 vs. control). EEO enhanced GSH and SOD and reduced ROS and MDA (P<0.01). Histology showed improved re-epithelialization, granulation, and angiogenesis. Caspase-3 staining indicated controlled apoptosis. Conclusion: EEO significantly enhances wound healing, possibly by modulating oxidative stress, inflammation, and apoptosis, thereby surpassing the efficacy of conventional therapy.
Introduction: Chrysin (CHY) is a naturally occurring flavonoid known for its anti-inflammatory and antioxidant properties. This systematic review aims to evaluate the photosensitizing and radiosensitizing effects of CHY and its nanoparticle (NP) formulations, and their potential to enhance therapeutic efficacy while reducing treatment-related adverse effects. Methods: This systematic review included 14 in vivo and in vitro studies published before October 21, 2025, that met specific inclusion and exclusion criteria. After screening, 14 studies met the inclusion criteria. Then information from each study was extracted and recorded. Subsequently, a risk-of-bias assessment was conducted for experimental studies, followed by a final analysis of the results. Results: CHY and its NPs, when combined with radiotherapy (RT) and phototherapy (PT), generate singlet oxygen (¹O₂) and various reactive oxygen species (ROS), causing photooxidative damage, DNA injury, cell-cycle arrest often at the G1 phase, and apoptotic cell death. Beyond direct cytotoxicity, CHY participates in key regulatory signaling pathways, including the modulation of apoptotic pathways, thereby enhancing apoptotic responses while increasing the production of inflammatory mediators. Under RT conditions, CHY and its nanoformulations boost γ-irradiation-induced tumor suppression by shifting the redox balance toward oxidative stress, increasing caspase-3 activity, and downregulating survival markers. Conversely, CHY shows notable protective effects in normal cells by reducing oxidative stress, neuroinflammation, and DNA damage through restoring antioxidant defenses, lowering lipid peroxidation, and maintaining neuronal integrity. Conclusion: Overall, CHY and its NPs suggest potential dual roles based on preclinical evidence as photo- and radiosensitizers while also providing protective effects against therapy-induced adverse outcomes.
Introduction: Ovarian cancer is a serious disease with high incidence and mortality in women, despite advances in surgical and medical therapies. Continuous efforts to develop safer and more effective treatments are crucial. The aim of this study was to explore the potential of 5,7-dihydroxy-3(R)-methylphthalide against ovarian cancer. Methods: This study utilized a bioinformatics approach with network pharmacology to collect active compounds and genes related to ovarian cancer, predict targets, perform network analysis, gene and pathway enrichment, molecular docking and molecular dynamics, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) prediction. Results: The bioinformatics approach revealed that the SRC protein was the most promising target among 28 potential target genes related to ovarian cancer influenced by the active compound. Molecular docking results indicated that the compound formed major hydrogen bond interactions with amino acid residues and exhibited relatively low binding energy values, indicating strong binding affinity. Molecular dynamics simulations confirmed the stability of the protein and ligand over 100 ns. MM-PBSA (Poisson-Boltzmann Surface Area Molecular Mechanics) analysis indicated lower binding energy for the compound. ADMET analysis indicated that the evaluated compounds did not violate the Lipinski, Ghose, Veber, and Egan rules, considering that the formulation changes showed no indication of cytotoxicity, mutagenicity, hepatotoxicity, neurotoxicity, cardiotoxicity, or immunotoxicity. Conclusion: The compound 5,7-dihydroxy-3(R)-methylphthalide has potential compared to its native ligand (1BU) and epirubicin as a control drug in targeting the SRC protein in ovarian cancer. Further in vitro and in vivo evaluation is needed to validate the activity.
Introduction: Metals are crucial for cellular physiology; however, their excessive accumulation triggers neuronal damage and leads to the progression of diverse neurodegenerative disorders, notably Alzheimer’s disease (AD). Accumulating evidence explored several plants and their active metabolites with established antioxidant properties as critical therapeutic interventions to allay metal-mediated neurotoxicity. In this avenue, both Rosa damascena and Commiphora wightii have demonstrated significant antioxidant and neuroprotective behaviours. Thus, the present research investigated the effects of R. damascena, C wightii, and their significant phytoconstituents, per se and in combinations, in the aluminum chloride (AlCl3)-induced neuronal damage in Drosophila. Methods: Following dose optimization via 7-day toxicity and 14-day survival assays, flies (50 per vial) were exposed to AlCl3 and various treatments for 7 consecutive days. On 7th day, the oxidative stress markers, the level of neurotransmitters and mitochondrial complexes were assessed following locomotion and memory assessment. Results: Results demonstrated that R. damascena and C. wightii per se enhanced motor activity and exhibited antioxidant potential in fruit flies, and their combination showed more significant improvement (P<0.001). Similarly, a noteworthy modulation in the mitochondrial complexes and neurotransmitter levels was also observed. Moreover, their phytoconstituents combination, i.e. geraniol and guggulsterone, respectively, was also found effective in mitigating the neurotoxic effect induced by AlCl3 overexposure, demonstrating a significant improvement in neuroprotective effect in flies. Conclusion: The overall outcomes suggest the potential of R. damascena and C. wightii or their combination as therapeutic agents for aluminum-induced neuronal toxicity and related neurodegenerative conditions.
Introduction: Milk kefir, a fermenting milk made with kefir grains, has shown potential in promoting apoptosis, regulating the cell cycle, and reducing tumor growth in breast cancer cells. This study aimed to investigate the stability and potential of milk kefir metabolites as inhibitors of breast cancer growth by interacting with the estrogen receptor alpha (ER-α), a key protein involved in breast cancer cell proliferation. We used computational methods, specifically molecular docking simulations with AutoDock and molecular dynamics (MD) simulations with Gromacs, to analyze how these metabolites bind to ER-α. Methods: A combination of molecular docking and MD simulations was used to explore how metabolites derived from milk kefir interact with ER-α, a crucial target in breast cancer therapy. The methodology included multiple stages: preparation of target proteins, preparation and screening of the metabolites, geometry optimization, molecular docking, and MD simulations. Results: The molecular docking simulations of 43 metabolites revealed three promising candidates: 2-Methyl (S35), benzeneethanol (S42), and 2,6-dimethyl-4-heptanone (S54), with binding affinities (ΔG) of -5.08, -5.06, and -4.90 kcal/mol, respectively. MD simulations further showed that the selected metabolites stabilized the ER-α-metabolite complex, with the 2,6-dimethyl-4-heptanone (S54) metabolite demonstrating the most negative total MM-GBSA energy value (ΔG = -22.98 kcal/mol), indicating a strong and stable binding interaction. Conclusion: 2,6-Dimethyl-4-heptanone, a metabolite from milk kefir, showed promising potential as a candidate for further development as a breast cancer treatment, offering a novel alternative to conventional therapies.
