Arterial hypertension is a worldwide challenging medical condition that continues to raise havoc despite existing treatments, prompting the need to develop new medicine. In a pilot study, we demonstrated that Tricalysia okelensis exhibits a vasorelaxant effect. This study evaluates the antihypertensive effect of the leaf aqueous (AETO) and ethanolic (EETO) extracts of T. okelensis against L-NAME-induced-hypertension, cardiac, and vascular remodeling. AETO and EETO underwent LC-MS/MS to identify potential metabolites responsible for the activity. Adult male Wistar rats were orally administered L-NAME (30 mg/kg/day) for 3 consecutive weeks. L-NAME administration was continued either alone or with captopril (20 mg/kg/day, p.o.), AETO, or EETO at doses of 85 and 170 mg/kg/day for another 3 consecutive weeks, while the naive group received the vehicle for 6 weeks. Blood pressure (BP) and heart rate were recorded before and weekly after the beginning of each treatment. Plasma angiotensin II (Ang II), serum nitric oxide (NO), lactate dehydrogenase (LDH), cardiac myeloperoxidase (MPO), and NO were assessed at the end of the experiment. Sections from the heart and aorta were analyzed for histological changes and immunohistochemical expression of atrial natriuretic peptide (ANP), endothelial (eNOS), and inducible (iNOS) nitric oxide synthases. AETO and EETO are rich in flavonoids and phenolic compounds. LC-MS/MS-based molecular networking enabled the putative annotation of several polyphenolic metabolites, including chlorogenic acid, neochlorogenic acid, rutin, quercetin derivatives, kaempferol derivatives, isorhamnetin, avicularin, and guaijaverin. L-NAME significantly increased BP and heart rate, Ang II, LDH, cardiac MPO, and heart weight (p < 0.05 - 0.001) while decreasing NO (p > 0.05). AETO and EETO reversed these alterations and also inhibited L-NAME-induced immune cell infiltration, fibrosis, cardiac and vascular eNOS downregulation, and iNOS overexpression, as well as ANP upregulation in heart tissue. AETO and EETO exhibit antihypertensive and anti-remodeling effects probably by modulating the renin-angiotensin system, improving endothelial function, and reducing inflammation and fibrosis.
Introduction:Azadirachta indica and Cryptolepis sanguinolenta are herbs commonly used together in polyherbal products in Ghana for the treatment of malaria. Aim:This research investigated the combined effects of Azadirachta indica and Cryptolepis sanguinolenta extracts against chloroquine-sensitive (3D7) and resistant (DD2) strains of Plasmodium falciparum. Methods:In vitro antimalarial activity was assayed on the aqueous extracts of both plants using a fluorescence-based SYBR Green assay. The combined effects of the two extracts were determined using computer-based software, CompuSyn. Results:Aqueous extracts of Azadirachta indica and Cryptolepis sanguinolenta exerted high antimalarial activities (IC50 ≤ 10 μg/mL) against both 3D7 and DD2 strains of the Plasmodium falciparum. Azadirachta indica and Cryptolepis sanguinolenta displayed strong synergistic activity with combination index (CI) values ranging from 0.15 to 0.52 for 53%-99% inhibition of 3D7 Plasmodium falciparum. Also, CI values for the plants against DD2 were from 0.23 to 0.61 with corresponding 30%-97% parasitemia inhibitions. Azadirachta indica and Cryptolepis sanguinolenta exerted a dose reduction index (DRI) value greater than 1 (DRI > 1) in both strains. Conclusion:Cryptolepis sanguinolenta and Azadirachta indica exerted synergistic interactions against 3D7 and DD2 strains of Plasmodium falciparum. The extracts are desirable when used in combination rather than alone.
Atherosclerosis develops as a persistent inflammatory condition that gradually alters the vascular structure and condition, in which the formation of macrophage-derived foam cells plays a central role in disease initiation and progression. Although proprotein convertase subtilisin/kexin type 9 (PCSK9) is widely recognised for its involvement in low-density lipoprotein receptor regulation and systemic lipid homeostasis, growing evidence indicates that PCSK9 also exerts a direct influence on macrophage inflammatory responses and intracellular lipid metabolism. Within atherosclerotic lesions, PCSK9 accelerates foam cell development by promoting oxidised low-density lipoprotein uptake, impairing cholesterol efflux through ABCA1 downregulation and activating key inflammatory pathways, particularly those mediated by TLR4/NF-κB and the NLRP3 inflammasome. This review emphasises recent findings that identify natural bioactive compounds as a novel and biologically relevant approach to counteracting PCSK9-driven inflammatory foam cell formation. Compounds such as salvianolic acid B, curcumin, quercetin, fisetin and myricetin display broad antiatherogenic properties by concurrently regulating macrophage polarisation, limiting scavenger receptor expression, suppressing inflammasome activation and modulating PCSK9 expression or function. In contrast to monoclonal PCSK9 inhibitors, which primarily address lipid lowering, these natural agents offer integrated anti-inflammatory and lipid-modulatory effects at the cellular level. Collectively, the evidence discussed in this review positions PCSK9 modulation by natural compounds as an emerging therapeutic concept that links lipid dysregulation with vascular inflammation. This multitarget strategy may complement current lipid-lowering therapies and support the development of more accessible and inflammation-focused interventions for atherosclerosis.
Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse event caused by drugs such as bortezomib, vincristine, paclitaxel, and oxaliplatin (L-OHP). This condition can lead to the discontinuation of anticancer drug administration and a diminished quality of life, posing a significant clinical problem. However, the only currently recognized effective treatment is duloxetine, and new therapeutic options are urgently required. Lentinula edodes mycelia extract (LEM) has been reported to improve CIPN in mouse models and alleviate numbness in patients with persistent neuropathy following L-OHP treatment. However, the active ingredients responsible for the attenuation of neuropathy remain unknown. We extracted the fractions from LEM, and an L-OHP-evoked allodynia mouse model was used to investigate which fraction contained the active ingredient. LEM was separated into an ethanol-soluble fraction (LES), an ethanol-insoluble fraction (LEP), and LEM(-), a hot water extract from the LEM-free medium. LEP abolished L-OHP-evoked allodynia, whereas LES and LEM(-) did not. In addition, fractionation of LEP based on molecular weight sieving yielded fractions LEP-1 (molecular weight ≥ 100,000) and LEP-2 (molecular weight < 100,000), the latter of which was found to inhibit L-OHP-evoked allodynia. Similarly, fractionation of LEP-2 gave rise to LEP-3 (molecular weight 3500-50,000) and LEP-4 (molecular weight ≤ 3500), the former of which had no inhibitory effects on L-OHP-evoked allodynia, whereas an inhibitory effect was observed in response to the administration of LEP-4. In addition, LEP-4 was found to abrogate the expression of NR2A and Cav3.2 mRNAs in the dorsal root ganglion (DRG), and inhibited the activation of extracellular regulated-protein kinase 1/2 (ERK1/2) in both the spinal cord and DRG. Moreover, oral administration of 0.25 g/kg LEP-4 ameliorated allodynia, which had developed following L-OHP administration. These findings indicate that the active component preventing CIPN in LEM resides in LEP-4. This compound has prophylactic and therapeutic potential for L-OHP-evoked allodynia by abrogating NR2A and Cav3.2 mRNA expression and activating ERK1/2.
Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator (SERM) approved for osteoporosis treatment, is attracting attention for drug repurposing, especially in cancer research. While designed primarily for estrogen receptors, BZA exhibits in vitro off-target interactions that may explain novel therapeutic benefits or account for potential side effects. This review comprehensively examines both established and newly identified targets of BZA beyond estrogen receptors. To gather relevant data, we reviewed over 1500 articles selecting key studies proposing insights into BZA targets and mechanisms. This review details BZA’s roles in estrogen receptor signaling and its interactions with glycoprotein 130, elaborating on vital components of each signaling pathway. It also compiles its potential interactions with cannabinoid receptors, as well as BZA targets related to biotransformation, absorption/transport, DNA cycle, Sars-CoV-2, ferroptosis, ROS production, and cholesterol biosynthesis. For each target, we discuss evidence from computational studies, direct interaction assay, and functional testing. This work provides the most complete overview of BZA’s molecular mechanisms to date and suggests new avenues for future research and potential applications beyond osteoporosis.
Background:Gentian violet (GV) is a broad-spectrum antimicrobial agent with documented efficacy against oropharyngeal candidiasis and periodontal pathogens, but its clinical use is limited by poor local retention. In situ forming matrices (ISMs) offer a promising strategy for sustained, localized drug delivery. Objectives:This study aimed to develop and evaluate GV-loaded ISMs using ibuprofen (IBU) and palmitic acid (PA) as dual-function matrix-forming agents in DMSO and NMP solvents for the localized treatment of oropharyngeal candidiasis and periodontitis. Methods:ISM formulations were prepared by simple mixing and characterized for viscosity, rheological behavior, injectability, mechanical properties, and in situ matrix formation. In vitro drug release of GV and IBU was quantified by a validated simultaneous HPLC method using an ACE C18 column with UV detection at 590 and 222 nm, respectively. Drug-release kinetics were modeled using zero-order, first-order, Higuchi, Korsmeyer-Peppas, and Peppas-Sahlin models. Antimicrobial activity against Staphylococcus aureus, Candida albicans, C. tropicalis, and Porphyromonas gingivalis was assessed by agar diffusion over 15 days. Molecular interactions were investigated using density functional theory (DFT) calculations at the B3LYP-D3BJ/6-31G(d,p) level. Results:All formulations showed Newtonian-flow behavior and acceptable injectability (0.78-1.50 N). GV and IBU release followed the Peppas-Sahlin model, with NMP-based systems releasing GV and IBU faster due to more porous matrix architecture, while DMSO-based systems formed denser matrices with slower release. All GV-containing formulations maintained antimicrobial inhibition zones for up to 15 days. DFT calculations revealed strong GV-IBU (-1.63 eV) and GV-PA (-1.53 eV) binding energies, supporting sustained drug entrapment. Conclusions:GV-loaded IBU/PA-based ISMs demonstrate sustained antimicrobial efficacy for up to 15 days with solvent-dependent release behavior. These systems show potential as localized, single-injection therapies for oral infections. Stability evaluation and in vivo biocompatibility studies are identified as necessary future steps.
Fingerroot (Boesenbergia rotunda (L.) Mansf.), a member of the Zingiberaceae family, exhibits anticariogenic activity against Streptococcus mutans. This study aimed to optimize ultrasound-assisted extraction and solvent system selection for oral spray development. Extraction conditions were optimized using a Box-Behnken design, evaluating ultrasonication time, solvent-to-solid ratio, and ethanol concentration. The optimal conditions-45-min ultrasonication, 30:1 solvent-to-solid ratio, and 85% ethanol-yielded the highest contents of pinocembrin, pinostrobin, and panduratin A. The optimized extract was then subjected to solvent system optimization using an I-optimal design to identify combinations of water, polyethylene glycol 400, and 95% ethanol for effective flavonoid recovery and solubilization. Three solvent systems (12:13:75, 10:30:60, and 6:60:34) were selected for oral spray formulation. Each formulation contained 0.03% sucralose, 0.3% menthol, 0.02% sodium methylparaben, and 0.18% sodium propylparaben. The resulting sprays demonstrated anticariogenic activity against S. mutans. Stability studies showed a decline in pH and flavonoid content over time, whereas viscosity and antimicrobial activity remained stable, as evidenced by inhibition zones. In summary, this study successfully combined extraction and solubilization optimization strategies to develop a fingerroot oral spray with potential anticariogenic properties.
Steroid-induced diabetes mellitus (SIDM) is a well-known side effect of corticosteroid agents. While diabetes induced by systemic corticosteroids has been extensively studied for over 60 years, evidence regarding the association between topical corticosteroids and Type 2 diabetes remains limited. This study aimed to investigate the relationship between topical corticosteroid use and the risk of Type 2 diabetes. A nationwide, population-based cohort study was conducted using data from the Korea National Health Insurance Service National Sample Cohort Database (NHIS-NSC2). A total of 186,057 adults without prior Type 2 diabetes were included in the cohort for follow-up. Among these, 14,944 adults who had been treated with topical corticosteroids and 171,113 adults with no history of topical corticosteroid use were included and followed prospectively for approximately 9 years. The primary outcome was the incidence of Type 2 diabetes following topical corticosteroid use, with additional analyses by frequency and potency of corticosteroid use. Kaplan-Meier curves and Cox proportional hazard models were used to estimate hazard ratios (HR) for Type 2 diabetes. The use of topical corticosteroids was significantly associated with an increased risk of Type 2 diabetes (adjusted HR [aHR] 1.13, 95% CI 1.06-1.20). The high-frequency corticosteroid group demonstrated the highest risk (aHR 1.27, 95% CI 1.09-1.48), while the moderate-potency corticosteroid group also showed a significant increase in risk (aHR 1.15, 95% CI 1.04-1.27). Notably, the diabetes risk in the moderate-potency group was comparable to that observed in the systemic corticosteroid group (aHR 1.20, 95% CI 1.14-1.26). In this study, the use of topical corticosteroids was significantly associated with the incidence of Type 2 diabetes. These findings highlight the importance of considering diabetes risk factors when prescribing topical corticosteroids.
Myocardial infarction (MI) involves a pathological process in which its association with ferroptosis is notably pronounced, and targeted regulation of ferroptosis presents a promising approach for treating MI. This work delineates the molecular basis by which the natural sesquiterpene germacrone protects against cardiomyocyte ferroptosis following isoproterenol (ISO)-induced MI. We established a murine model of ISO-induced MI, paired with an injured H9c2 cardiomyocyte model in vitro. Mice in the experimental group received daily oral germacrone (25, 50, and 100 mg/kg) for 7 consecutive days. We profiled myocardial injury markers and key nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) axis proteins. The mechanism of action was confirmed by utilizing ML385, the Nrf2-specific inhibitor. Germacrone significantly reduced ISO-induced myocardial injury in mice, improving cardiac function and decreasing myocardial histopathological damage. Germacrone universally attenuated the elevation of myocardial injury and inflammatory markers in all experimental models. It also decreased the apoptosis rate of H9c2 cells. Germacrone inhibited myocardial ferroptosis and upregulated the abundance of pivotal regulatory proteins, including Nrf2, GPX4, and heme oxygenase-1 (HO-1), along with solute carrier family 7 member 11 (SLC7A11). ML385, an Nrf2 antagonist, can block germacrone's protective effect against ISO-induced myocardial ferroptosis and reverse its upregulation of these pathway proteins. These findings provide a new potential target and experimental foundation for MI treatment.
The worldwide prevalence of allergic rhinitis (AR) is substantial and is considered a global health problem. Allergen immunotherapy (AIT) is the only approach that treats the underlying cause of allergy by inducing a desensitization response to the allergen. In this study, we investigated the effectiveness and the possible desensitization mechanisms of house dust mite (HDM) allergen extract-based IT against mice models of AR. The experimental mice were divided into six groups: normal group, normal group with HDM challenge, AR group, and three AR groups that received HDM-IT at low, moderate, and high doses. The effectiveness of HDM-IT was evaluated based on nose-rubbing and sneezing behavior, IL-4 mRNA expression, eosinophil infiltration into nasal mucosal tissue, serum IgE levels, serum IgG2a levels, and serum IgE/IgG2a ratio. This study discovered that the administration of HDM-IT reduced nose-rubbing and sneezing behavior, decreased IL-4 mRNA expression and eosinophil infiltration into nasal mucosal tissue, decreased serum IgE levels, increased serum IgG2a levels, and decreased serum IgE/IgG2a ratio in AR mice. Thus, HDM-IT effectively promotes a desensitization response to HDM allergens in mouse models of AR.
The etiological contribution of male factors to infertility remains a significant concern in reproductive health. Natural dietary products are gaining attention as promising interventions to improve male infertility. This study investigates the effects of aqueous extract of Sesamum indicum L. (S. indicum) on male reproductive parameters and potential anti-infertility mechanisms. Male Sprague-Dawley rats were randomly assigned to five groups: a control group (distilled water), two treatment groups receiving aqueous S. indicum extract (1.5 and 3.0 g/kg) for 30 days, and corresponding recovery groups. Reproductive organs were assessed for weight and sperm parameters. Blood serum was analyzed for luteinizing hormone (LH), testosterone, and lipid profile parameters. Incorporating in silico approaches, bioactive compounds of S. indicum were screened from a database, and their targets were predicted via network pharmacology, followed by functional enrichment analyses and molecular docking. Findings show that S. indicum significantly increased (p < 0.05) the weights of the hearts, adrenal glands, livers, and accessory reproductive organs. Sperm count and morphology, as well as LH and testosterone levels, were significantly increased (p < 0.05). Network pharmacology identified linoleic acid, oleic acid, biotin, and esculentic acid as key contributors to the extract's anti-infertility effects, potentially via interactions with EGFR, HIF1, BCL2, TNF, and AKT1. These interactions, supported by favorable binding affinities, may involve antioxidative pathways. Although the exposure duration, differences in extraction methods, paucity of experimental molecular data, and algorithmic constraints represent potential limitations, the present findings provide pharmacological insights into the therapeutic role of S. indicum in male infertility.
Objective:Desmos chinensis (Annonaceae) is an underexplored medicinal plant from Southeast Asia with limited pharmacological validation. This study investigated, for the first time, the analgesic, anti-pyretic, anti-inflammatory, and anti-arthritic potential of the methanolic extract of D. chinensis leaf and its solvent-soluble fractions (n-hexane, dichloromethane, and ethyl acetate) using in vivo, in vitro, and in silico approaches. Methods:Analgesic activity was assessed using the acetic acid-induced writhing method; anti-pyretic activity was assessed using the brewer's yeast-induced pyrexia model; anti-inflammatory activity was assessed using protein denaturation; and anti-arthritic activity was assessed using the human red blood cell membrane stabilization method. Result:In the writhing test, the ME and ethyl acetate fractions at 400 mg/kg produced marked analgesic effects, with 86.36% and 65.91% inhibition of writhing, respectively, compared with diclofenac (90.45%). In the anti-pyretic model, ME significantly reduced yeast-induced hyperthermia, achieving up to 100% reduction in pyrexia within 4 h at 400 mg/kg (p < 0.001). In vitro assays showed concentration-dependent anti-inflammatory and anti-arthritic activities. ME inhibited protein denaturation with an IC50 of 337.42 μg/mL, while HRBC membrane stabilization revealed strong anti-arthritic potential with an IC50 of 246.34 μg/mL, comparable to diclofenac sodium. Docking analysis revealed favorable interactions between phytoconstituents and inflammation-related targets. Conclusion:This study provides the first integrated pharmacological evidence that D. chinensis leaves possess significant analgesic, anti-pyretic, anti-inflammatory, and anti-arthritic activities. The quantitative efficacy and in silico findings highlight D. chinensis as a promising source of bioactive compounds, warranting further isolation, mechanistic, and preclinical investigations.
Background:This study is designed to overcome the limitations of transdermal drug delivery by developing a customized iontophoretic device to rapidly increase the delivery of NSAIDs (diclofenac sodium [DS]). Methods:Three concentrations of DS topical solution were prepared. A customized iontophoretic device has been designed to study the effect of the device in vitro, ex vivo, and in vivo on the release of DS topical solution. Results:Release of DS using an iontophoretic device was found proportional to the drug concentration with respect to time and current applied, i.e., 2.0% solution showed more promising drug release than 1.5% and 1.0%. Likewise, the release rate of DS is much higher at 5 mA than at 1 mA current. The most prominent in vitro concentration of DS (2%) showed a significant reduction in the rat's paw size compared with the in vivo control and passive control groups. Conclusion:The consistency of these results across both ex vivo and in vivo studies underscores the efficacy and preclinical proof-of-concept for this iontophoretic technique. While these results are promising, further studies on long-term skin tolerability and irritation are required to establish its safety profile for human use in enhancing drug delivery. This work provides a solid foundation for further development of noninvasive drug delivery systems for topical applications, offering a promising approach for improving therapeutic outcomes.
An acne treatment patch was developed by incorporating Rhodomyrtus tomentosa (RT) leaf extract into hyaluronic acid serum, followed by integration with high-quality block natural rubber using a two-roll milling process. RT hyaluronic acid serum exhibited strong antibacterial activity against pathogens associated with acne vulgaris. The minimum inhibitory concentrations and minimum bactericidal concentrations ranged from 0.39% to 12.5% and 0.39% to 25%, respectively. Acne patches containing RT hyaluronic acid serum (RT patch) were evaluated for their structural, mechanical, and physical properties. Atomic force microscopy revealed changes in surface roughness due to the incorporation of RT serum into the rubber matrix. FTIR spectroscopy confirmed the successful incorporation of RT serum into the patch, with no chemical interactions observed. The peel and shear strength of the RT patch were 1.46 & times; 10-2 N/m and 3.76 & times; 104 N/m2, respectively. RT patches had a water contact angle of 109 degrees, indicating hydrophobic surfaces. The dry patch could absorb up to 900 times its weight in solution and release rhodomyrtone, the major bioactive component of RT extract. The amounts of rhodomyrtone released at 2, 8, and 12 h were 0.241 +/- 0.001, 0.246 +/- 0.001, and 0.202 +/- 0.001 mg/L, respectively. Antibacterial activity of RT patches was evaluated using an ex vivo porcine skin infection model. The developed patches demonstrated potent antibacterial activity by inhibiting S. aureus and S. epidermidis by more than 99.9%, compared to blank patches. RT patches exhibited significant scavenging activity and showed no cytotoxic effects on L929 fibroblast cells. In addition, both RT serum and RT patch suppressed the inflammatory process by reducing nitric oxide production in macrophage cells, resulting in decreases of up to 80% and 60%, respectively. The findings highlight the promising potential of the RT patch as an effective alternative for the treatment of acne vulgaris.
Background and Aim Anemia affects billions, primarily young women and men. Taking steroids and immunosuppressants might cause side effects. So recent studies are focusing on natural hematinic agents to cure anemia. This study examined Artocarpus chaplasha seeds against phenyl hydrazine-induced hemolytic anemia in Swiss albino mice. Methods To induce anemia, mice administered 60 mg/kg phenyl hydrazine intraperitoneally for 2 days. On Day 3, decreased RBC, hemoglobin, and hematocrit levels revealed anemia. Mice were orally treated with A. chaplasha seed methanol extract. Vitamin B-12 was the reference standard. Post 200 and 400 mg/kg test extract administration, blood was taken for hematological analysis on Day 15. All in vivo results were analyzed and supported through in silico approach. Results Compared to positive control group, A. chaplasha seeds doses of 200 and 400 mg/kg significantly ((& lowast;& lowast;)p < 0.01) increased RBC levels. Hemoglobin levels considerably increased with 200 mg/kg ((& lowast;)p < 0.05) and 400 mg/kg ((& lowast;& lowast;)p < 0.01). The 200 and 400 mg/kg doses significantly elevated hematocrit (PCV) levels ((& lowast;)p < 0.05 and (& lowast;& lowast;& lowast;)p < 0.001). Furthermore, in silico molecular docking studies showed significant binding affinity of the compounds against the receptor protein (PDB ID: 2HHB). With -7.2 kcal/mol, neophytadiene bound strongly. Conclusion The in vivo activity demonstrate increase in the RBC level, and docking score shows comparability to the positive control, folinic acid with a score of -6.9 kcal/mol. Thus, the A. chaplasha seed may be a promising natural anemic treatment.
Purpose This study aimed to identify high-risk drugs for drug-induced extrapyramidal disorder (EPD) and explore their molecular mechanisms by integrating pharmacovigilance analytics with genetic and computational approaches. Methods We performed disproportionality analysis on FAERS data (2004-2024) to detect EPD signals, time-to-onset analysis to assess risk timing, Mendelian randomization (MR) to infer causal effects of drug-target gene expression (e.g., HTR1D, ADRA2B) on EPD risk, and molecular docking to evaluate drug-target binding affinities. Results Metoclopramide, risperidone, and haloperidol decanoate showed the strongest EPD signals. TTO analysis revealed an early failure pattern (Weibull beta < 1), indicating highest risk during initial treatment. MR identified brain-expressed HTR1D and ADRA2B as causally linked to EPD risk. Molecular docking confirmed strong binding of risperidone and paliperidone to these targets. Conclusions This study is the first to integratively link pharmacovigilance signals with genetic causality and structural binding insights for EPD. Our findings support deprescribing high-risk agents, preemptive genetic screening, and enhanced early monitoring to mitigate drug-induced EPD, offering a translational framework for precision pharmacovigilance.
Breast cancer remains the most prevalent cancer in women globally, with cases projected to exceed 3 million by 2040. Current treatments, including chemotherapy with 5-fluorouracil (5FU), are often hindered by multidrug resistance (MDR) and significant toxicities. This study investigated the potential of lutein (Lut), a bioactive xanthophyll with pro-oxidant activity that could enhance 5FU's efficacy while reducing the dosage in MCF-7 cells analyzed via CompuSyn software. The result revealed that the Lut:5FU combination at a ratio of 0.25:1 had a synergistic effect at Fraction affected (Fa) of 0.49 with a combination index (CI) value of 0.09, indicating synergistic effects (CI < 1), and the dose-reduction index (DRI) of Lut and 5FU was 11.27- and 277.16-fold, respectively. Moreover, Lut encapsulation in niosomes could protect Lut's photodegradation, offer controlled release, and enhance cancer cell inhibition. In addition, the total cell death of Lut:5FU encapsulated in niosomes (Lut:5FU-N) was investigated by apoptosis assay, which was the highest efficacy at 43.11 +/- 3.29% compared to Lut encapsulated in niosomes (Lut-N) and 5FU encapsulated in niosomes (5FU-N) as a single treatment (32.27 +/- 1.17 and 24.97 +/- 1.96%, respectively). This study presented that Lut could improve the therapeutic efficacy of 5FU by combination and encapsulation in niosomes for breast cancer treatment, providing a promising strategy to enhance anticancer effects, address the limitations of conventional cytotoxic agents, and mitigate associated toxicities.
Six new phenyl-1H-pyrazole-carbaldehyde isonicotinylhydrazone derivatives 1-10 were synthesized and characterized by spectroscopic (FT-IR, 1H NMR, and 13C NMR) techniques and electrospray ionization-mass spectrometry (ESI-MS). Homonuclear data from 2D-NMR (1H-1H NOESY) revealed that 3 and 5 adopt the transE isomeric form. The in vitro antitubercular activity of all the synthesized compounds was determined against Mycobacterium tuberculosis (sensitive H37RV and resistant TB DM97). With respect to the isoniazid (INH) standard drug (MIC = 0.91 mu M), all the prepared compounds showed greater antitubercular activity with MIC values in the range of 0.38-0.82 mu M against Mtb H37Rv-sensitive strain. However, the preliminary results indicated that Compounds 1-10 tested against the TB DM97-resistant strain showed low bioactivity. The optimized geometry of Compounds 1-10 has been determined by density functional theory (DFT) calculations. For Compounds 1-6, the most stable isomers (in DMSO) exhibited an E geometrical configuration, while Compounds 7-10 exhibited a Z configuration. The global reactivity values indicate that Compounds 1-10 are slightly more reactive and less stable than the standard (INH). Additionally, they exhibit a strong binding capacity to biomolecules, comparable to INH. The MEP map reveals that the negative and positive potential sites are predominantly located on the C=O and HN-NH groups, respectively, similar to those observed for INH. Drug-likeness and ADME properties were evaluated. All compounds showed adequate ADME properties and are drug-like. Molecular docking studies (Compounds 1-10) into the active site of mycobacterial InhA showed an acceptable dissociation constant with improved binding energy (from -6.7 to -8.1 kcal mol-1) compared to isoniazid (-5.6 kcal mol-1). Molecular dynamics simulations revealed that the molecules cmp3 (3) and cmp5 (5) form stable ternary complexes with InhA through persistent hydrogen bonding and hydrophobic interactions. These compounds showed reduced active-site fluctuations and superior binding free energies compared to INH. The findings represent a significant advancement in the discovery of potential antitubercular agents.
Laportea decumana (Roxb.) Wedd. is known for its analgesic, antioxidant, anti-inflammatory, and antibacterial properties. This study aimed to evaluate the wound-healing effects of LDE incorporated into a biocellulose dressing for the treatment of polymicrobial-infected wounds. The metabolite profile of LDE was characterized using UPLC-Q-TOF/MS. Biocellulose dressings were prepared with and without 4% LDE for the in vivo study. Fifteen male rats were each subjected to three biopsy punch wounds, which were infected with a polymicrobial mix of Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa. The wounds were treated with either blank or 4% LDE-fortified biocellulose dressing, or left untreated for 14 days. Wound diameters were measured daily, and histological analyses were conducted on Days 3, 7, and 11 to evaluate the inflammatory, proliferative, and maturation phases of wound healing. In vivo experiments showed that wounds treated with 4% LDE-fortified biocellulose had significantly smaller diameters from Day 11 onward compared to untreated wounds or blank control. While all wounds exhibited edema and leukocyte infiltration during the inflammatory phase, treatment with 4% LDE significantly enhanced granulation tissue formation, fibroblast activity, and collagen deposition in the proliferative phase. During maturation, LDE-fortified dressings accelerated re-epithelialization. In conclusion, the 4% LDE-fortified biocellulose dressing exhibited wound-healing effects in a rat model of infected wounds by promoting cell proliferation and accelerating the maturation phase of wound repair. Further studies are needed to clarify the underlying antimicrobial and inflammatory mechanisms.
Aim: Myrtus communis is a medicinal plant known for its pharmacological potential against cardiovascular, metabolic, and infectious disorders. This study aimed to analyze the phytochemical composition of Myrtus communis essential oil (MCEO) and to evaluate its antioxidant, antimicrobial, and antidiabetic activities through in vitro and in silico approaches. Methods: The chemical profile of MCEO was determined by gas chromatography-mass spectrometry (GC-MS). Antioxidant activity was assessed using DPPH and FRAP assays. Antimicrobial activity was evaluated against Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and yeasts (Candida albicans and Candida krusei) using the broth microdilution method. Antidiabetic activity was tested by measuring the inhibition of alpha-amylase and alpha-glucosidase. To complete the experimental results, ADMET and molecular docking analyses were performed. Results: GC-MS analysis identified 1,8-cineole (54.84%), p-cymene (19.42%), and beta-pinene (4.66%) as the major constituents of MCEO. The oil exhibited notable antioxidant activity, showing free radical scavenging in the DPPH assay and strong reducing capacity in the FRAP assay. Antimicrobial testing revealed significant effects against all strains, with minimum inhibitory concentrations (MICs) ranging from 0.019% to 0.312% (v/v) for bacteria and from 0.019% to 0.078% (v/v) for fungi, suggesting potential bactericidal and fungicidal properties. Furthermore, MCEO demonstrated moderate inhibitory activity on alpha-amylase (IC50 = 0.179 +/- 0.091 mg/mL) and a statistically significant but lower inhibition of alpha-glucosidase (IC50 = 0.086 +/- 0.017 mg/mL, p < 0.001). Conclusion: The results indicate that MCEO possesses promising antioxidant, antimicrobial, and moderate in vitro alpha-amylase and alpha-glucosidase inhibitory activity. These findings suggest its potential as a natural source for the development of new pharmacological agents.
