Dental caries is a highly prevalent and costly biofilm-dependent disease that affects about 2.3 billion people in their permanent teeth and 532 million people in their primary teeth according to the World Health Organization. The condition is often accompanied by inflammation of the pulp and root apex. Given the high cost of dental procedures, and also the toxicity and antimicrobial resistance linked to antibiotic use, emphasis should be placed on prevention and alternative therapies. Hence, the present study was aimed at evaluating the ethnopharmacology of some plants used in the management of dental caries.Information on plant use, indications, and preparation methods was collected from participants (dental caries patients and traditional medicinal practioners) using the snowball/purposive sampling technique. Quantitative phytochemical analysis and evaluation of free radical scavenging (antioxidant) activity of hydroethanolic extracts were done using spectrophotometry. Anticariogenic activity was assessed in vitro using antibacterial broth microdilution and antibiofilm assays, while lytic and outer membrane permeability activities were also determined spectrophotometrically.Twenty participants reported the effectiveness of medicinal plants in the management of pulpitis, leading to the documentation of 14 plant species. Phytochemical analysis revealed varying concentrations of the assayed compounds. ET (Vitellaria paradoxa) had the highest total phenol content (142.57 ± 2.49 mg GAE/g), while total flavonoid and tannin contents were dominated by PB (Persea americana) (39.04 ± 2.31 mg QE/g) and EP (Euphorbia prostata) (18.46 ± 0.75 mg TAE/g) respectively. Antioxidant evaluation showed notable activities, with EP (Euphorbia prostrata) demonstrating the strongest DPPH radical scavenging activity (IC₅₀ = 1.12 ± 0.11 µg/mL) and FRAP activity (135.03 ± 0.33 µmol FeSO₄/g), as well as concentration-dependent hydroxyl radical scavenging activity. ET (Vitellaria paradoxa) showed the highest antibacteial activities of 64 and 128 µg/ml respectively for MIC and MBC and also demonstrated the strongest antibiofilm activity, with inhibition and eradication rates of 92.72 ± 2.68% and 81.41 ± 0.08%, respectively. In addition, PB (Persea americana) showed the highest lytic activity while ET (Vitellaria paradoxa) produced the highest outer membrane permeability effect.Hydroethanolic extracts of plants in the present study showed good anticariogenic and antioxidant activities. The high phenolic contents could explain their use as anti-inflammatories. These findings suggest that the studied plants and their bioactive constituents may serve as potential sources of novel anticariogenic agents for the prevention and management of dental caries.
Cisplatin is a prevalent anti-tumor agent despite its association with DNA damage, oxidative stress, myelosuppression, and hepatotoxicity, which may limit its use. The current study aims to assess the mitigating effect of selenium on cisplatin-induced hepatotoxicity. Thirty-two adult albino rats were evenly divided into four groups: the control group received normal saline, the CIS group was IP injected with a single dose of cisplatin (7.5 mg/kg BW) on the 22nd day, the SE group received selenium (1 mg/kg BW, orally) for 21 days, and the SE + CIS group received selenium daily followed by a single IP dose of cisplatin. Samples were collected for hemogram, liver function tests, hepatic redox status, expression of pro- and anti-inflammatory cytokines, and evaluation of pro-apoptotic proteins. In the CIS group, hepatobiliary enzymes, bilirubin, cholesterol, triglycerides, blood glucose, hepatic MDA, and TNF-α mRNA expression increased significantly (P ≤ 0.001) and correlated positively (r = 0.99-0.80) with hepatocyte necrosis, pro-apoptotic Bax, and Caspase-3 markers immunoreactivity. Total protein, albumin, globulin, SOD, CAT, GSH, and IL-10 expression significantly decreased (P ≤ 0.001) and correlated negatively (r = -0.99 to -0.80) with hepatopathies and pro-apoptotic marker expression. Indeed, hepatic damage scores and immunoreactivity for the pro-apoptotic markers Bax and caspase-3 were significantly ameliorated in the SE + CIS group. These mitigations showed strong correlations with improved liver function panel results, antioxidant capacity, and hepatocyte expression of IL-10 and TNF-α. Pretreatment with selenium mitigates cisplatin-induced hepatocellular toxicity by promoting IL-10 expression, quenching free radicals, and activating downstream Bax/Caspase-3 apoptotic signaling cascades.
Antioxidant activity is commonly discussed in fields like chemistry, biology, nutrition, and medicine, but it is often viewed in functional terms rather than as a process controlled by basic radical kinetics. In many cases, antioxidant efficiency is described within a simple scavenging model, where antioxidants mainly intercept reactive radicals stoichiometrically and are then irreversibly consumed. While this model highlights an important aspect of antioxidant behavior, it does not fully capture the complexity of oxidative processes.In this review, antioxidant chemistry is examined as a competitive reaction network where chemical repair and regeneration pathways play a key mechanistic role. These pathways allow for the restoration of radical intermediates before damage terminates and enable the recycling of oxidized antioxidant species, thus extending antioxidant activity beyond just radical trapping. In this context, the identity of radicals, branching ratios, oxygen-dependent competition, and radical lifetimes are crucial factors that determine whether oxidative processes lead to propagation, termination, or repair.Special focus is given to phenolic antioxidants and to reaction networks involving the hydroperoxyl/superoxide couple (HO2•/O2•-). Although superoxide is often described as a weak oxidant or a precursor to more reactive species, its reactivity depends heavily on conditions. Under the right kinetic conditions, superoxide can participate in reductive pathways that contribute to antioxidant regeneration and radical repair.By combining insights from radiation chemistry, electrochemistry, and computational kinetics, this review highlights chemical repair as an important mechanistic component of antioxidant activity and offers a unified framework for understanding antioxidant function in various chemical and biological settings.
Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) were once regarded solely as toxic environmental gases. However, accumulating evidence over the past several decades has established them as the three principal endogenous gasotransmitters that regulate a wide spectrum of physiological and pathological processes. Unlike conventional signaling molecules, gasotransmitters diffuse freely across biological membranes and exert potent biological effects through receptor-independent mechanisms, including redox-sensitive post-translational modifications and modulation of heme-containing proteins. Although the individual functions of NO, CO, and H2S have been extensively reviewed, emerging studies indicate that these gaseous mediators rarely operate in isolation. Instead, they form a highly integrated signaling network characterized by direct chemical interactions, reciprocal enzymatic regulation, and convergence upon common downstream pathways. In this mini-review, we propose the concept of a "Gasotransmitter Trio Network," emphasizing the molecular crosstalk among NO, CO, and H2S as a fundamental determinant of cellular homeostasis. We first summarize the biosynthetic pathways and major signaling mechanisms of the gasotransmitter trio, including S-nitrosylation, persulfidation, and heme-dependent regulation. We then discuss recent advances revealing how interactions among these gases generate novel bioactive intermediates and coordinate redox signaling. Particular attention is given to the emerging roles of gasotransmitters in regulating ferroptosis, autophagy, and mitophagy by modulating iron metabolism, lipid peroxidation, mitochondrial quality control, and antioxidant defense systems. These findings support a unified framework in which gasotransmitters function as master regulators of cellular fate under conditions of physiological and pathological stress. Finally, we highlight recent progress in stimuli-responsive donors, CO-releasing molecules (CORMs), NO-releasing materials (NORMs), H2S donors, and advanced nanoplatforms that enable spatiotemporally controlled gas delivery. We propose that future therapeutic strategies will increasingly rely on programmable multi-gas systems that recapitulate endogenous gasotransmitter networks. Collectively, this review provides a systems-level perspective on gasotransmitter biology and outlines emerging opportunities for the development of precision gas medicine in cardiovascular, neurodegenerative, inflammatory, metabolic, and malignant diseases.
Real-time visualization of oxidative stress in living systems poses a formidable challenge in epilepsy research, primarily due to the scarcity of tools capable of selectively distinguishing structurally similar reactive oxygen species (ROS) with high specificity. Here, we present a dual-functional fluorescent probe, HH, capable of independently detecting hydrogen peroxide (H2O2) and hydroxyl radicals (•OH) through distinct recognition mechanisms, yielding spectrally resolved signals with high sensitivity, selectivity, and biocompatibility. HH enables high-resolution, interference-free imaging of redox dynamics in both gasdermin-mediated pyroptosis and pentylenetetrazol (PTZ)-induced epileptic cell models. Furthermore, HH was successfully employed in PTZ-induced zebrafish and kainic acid (KA)-induced mouse epilepsy models, revealing elevated ROS levels under seizure-like conditions. Notably, ROS-targeted therapeutic interventions significantly modulated oxidative profiles, demonstrating HH's potential for therapeutic evaluation. This work not only fills a critical methodological gap in ROS biology and epilepsy research but also provides a versatile platform for studying redox regulation in neurological and inflammatory diseases and enabling mechanistic and therapeutic investigations.
Sex-related differences in kidney cancer incidence and tumor biology are well established; however, their impact on peri‑operative performance and long-term oncologic outcomes after surgery remains incompletely characterized. We evaluated the association between biological sex and surgical, pathological, and oncologic outcomes in a large contemporary cohort. We retrospectively analyzed a prospectively maintained institutional database including patients undergoing partial or radical nephrectomy as primary treatment for kidney cancer at a high-volume tertiary center (1987-2024). Peri-operative outcomes, adverse pathological features, and long-term oncologic endpoints were compared according to biological sex. Multivariable regression models were used to adjust for baseline clinical, surgical, and tumor-related confounders. Survival outcomes were assessed using Kaplan-Meier estimates and Cox proportional hazards models. In addition, a sensitivity analysis restricted to patients treated between 2005 and 2020 (n = 2,227) was performed to evaluate the robustness and contemporary applicability of the findings. Overall, 3,956 patients were included, of whom 30.5% were female. After multivariable adjustment, male sex was independently associated with longer operative time (β: 13, 95% confidence interval [CI] 6.3-19; P < 0.001) and a higher risk of post-operative acute kidney injury (odds ratio [OR] 1.49, 95% CI 1.21-1.84; P < 0.001), but not with major complications, peri‑operative transfusions, or prolonged length of stay (all P > 0.5). From a pathological standpoint, male patients were more likely to harbor high-grade tumors (OR 1.52, 95% CI 1.19-1.96; P = 0.001) and tumor necrosis (OR 1.38, 95% CI 1.10-1.75; P = 0.006). While biological sex was not independently associated with relapse-free, progression-free, or overall survival (all P > 0.1), male patients exhibited a significantly higher risk of progression at unfavorable metastatic sites (hazard ratio 1.78, 95% CI 1.09-2.89; P = 0.02). Importantly, these findings showed consistent directionality and statistical significance in the contemporary surgical era sensitivity analysis. Biological sex emerged as a relevant determinant of peri‑operative outcomes, tumor aggressiveness, and patterns of disease progression in surgically treated kidney cancer patients. Male sex was independently associated with less favorable peri‑operative metrics, adverse pathological features, and a higher risk of progression at unfavorable metastatic sites, although these differences did not independently translate into worse long-term relapse-free, progression-free, or overall survival.
The mesorectal and anti-mesorectal sides of the rectum differ considerably in embryonic origin, blood supply, lymphatic distribution, and anatomical relations. Tumor location (mesenteric vs. anti-mesenteric) may therefore influence tumor biology and clinical outcomes. This study aimed to evaluate the impact of axial tumor location on clinicopathological features and prognosis in rectal cancer using preoperative high-resolution pelvic MRI. We retrospectively reviewed 380 rectal cancer patients who underwent radical resection between January 2017 and July 2023. Based on preoperative MRI axial images, tumors were classified by their deepest point of invasion relative to the rectal lumen: the mesenteric side group (3-9 o'clock, posterior/posterolateral walls, n=213) and the anti-mesenteric side group (9-3 o'clock, anterior/anterolateral walls, n=167). Demographic, clinicopathological, surgical, and survival data were compared between groups. Among the 380 patients, 213 were assigned to the mesenteric side tumor group and 167 to the anti-mesenteric side tumor group. Baseline characteristics, including age, gender, BMI, TNM stage, MRF status, EMVI, and vascular/nerve invasion, did not differ significantly between two groups (all P > 0.05). With a median follow-up of 56 months, the 3-year local recurrence-free survival (LRFS) rate was significantly lower in the anti-mesenteric group than in the mesenteric group (91.6% vs. 97.1%, P = 0.029). No significant differences were observed in 3-year disease-free survival (83.2% vs. 82.1%, P = 0.832) or overall survival (85.6% vs. 81.7%, P = 0.501) between the two groups. Multivariable Cox regression analysis identified age (HR = 1.043, P = 0.002), surgical procedure (APR vs. LAR, HR = 1.967, P = 0.022), pathological T stage (HR = 2.800, P = 0.023), and pathological N stage (HR = 3.683, P < 0.001) as independent prognostic factors for overall survival. Pathological N stage was the sole independent predictor for disease-free survival (HR = 3.088, P < 0.001). Although axial location was not an independent predictor of overall or disease-free survival (P > 0.05), it was significantly associated with LRFS (anti-mesenteric vs. mesenteric: HR = 2.684, 95% CI: 1.126-6.398, P = 0.026) along with pathological N stage (HR = 3.960, 95% CI: 1.316-11.919, P = 0.014).These findings suggest that anti-mesenteric tumor location is an independent predictor of increased local recurrence risk, providing valuable information for surgical planning and postoperative surveillance beyond conventional staging. Anti-mesenteric rectal tumors are associated with a higher risk of local recurrence, likely due to complex local anatomy and surgical challenges. While pathological N stage, pathological T stage, age, and surgical procedure remain primary independent prognostic factors for survival outcomes, preoperative MRI assessment of axial location provides valuable supplemental information that may help stratify local recurrence risk, refine surgical planning, and optimize postoperative monitoring.
Hypertension is a major contributor to cardiovascular morbidity and mortality, largely driven by oxidative stress, mitochondrial dysfunction, endothelial injury, and chronic vascular inflammation. Emerging evidence suggests that targeting vascular bioenergetics may provide complementary therapeutic strategies beyond conventional antihypertensive drugs. This review explores the mitochondrial protective mechanisms of Piper retrofractum and its major bioactive compounds in the context of hypertension and oxidative vascular injury. The phytochemical profile of P. retrofractum, particularly piperine, piplartine, pipernonaline, and retrofractamides, demonstrates significant antioxidant, anti-inflammatory, and metabolic regulatory activities. Mechanistically, these compounds may attenuate mitochondrial reactive oxygen species (mtROS), restore endothelial nitric oxide synthase (eNOS) coupling, activate AMPK-SIRT1-PGC-1α signaling, induce Nrf2-HO-1 antioxidant pathways, and modulate mitochondrial dynamics and mitophagy. Collectively, these effects contribute to improved endothelial function, reduced vascular remodeling, suppression of inflammatory cascades, and enhanced mitochondrial resilience. In addition, emerging omics technologies, network pharmacology, and AI-assisted nutraceutical discovery offer new opportunities to elucidate multitarget mechanisms and optimize P. retrofractum-based interventions. Despite promising preclinical evidence, important limitations remain, including insufficient clinical studies, limited mitochondrial-specific investigations, and challenges related to bioavailability and standardization. Overall, P. retrofractum represents a promising mitochondria-centered nutraceutical candidate for hypertension management and vascular protection, warranting further translational and clinical investigation.
A catalyst-free visible-light-induced protocol for the C4-selective C-H arylation of pyrimidine derivatives has been developed using arylazo sulfones as aryl radical precursors. Under mild conditions and without external photocatalysts or transition metals, a broad range of arylated pyrimidines were obtained in moderate to excellent yields. Mechanistic studies, including radical trapping experiments and light-control tests, support a visible-light-triggered radical pathway. Selected compounds exhibited promising antiproliferative activities against A549 and MCF-7 cell lines.
The design, synthesis, and biological assessment of new heterocyclic compounds containing the 1,3,4-thiadiazole moiety, a well-known pharmacophore with substantial medicinal significance, are the main topics of this study. To create a variety of thiadiazole-based heterocyclic systems, such as pyrazoles, triazoles, pyrimidines, and thiophenes, a novel cyanoacetohydrazide derivative was created and used as a crucial intermediate. IR, 1H-NMR, 13C-NMR, and mass spectrometry were the spectroscopic methods used to confirm the structures of produced compounds. The synthesized compounds' biological properties were assessed for their potential as antioxidants and anticancer agents. Several derivatives showed impressive activity in cytotoxicity tests against HePG-2 and MCF-7 cancer cell lines, with several compounds showing greater potency than the reference medication 5-fluorouracil. Compounds 17, 18, and 13 exhibited the strongest anticancer activity, highlighting the significance of structural and electronic properties in improving biological performance. Furthermore, an assessment of the synthesized compounds' antioxidant activity revealed that they have differing levels of free radical scavenging activity, with compounds 17 and 18 exhibiting the most notable benefits, albeit still less than ascorbic acid. Electron-donating and electron-withdrawing groups, molecular conjugation, and lipophilicity all play a part in regulating antioxidant and anticancer actions, according to structure-activity relationship (SAR) studies. Additionally, substantial interactions between specific drugs and the EGFR tyrosine kinase domain were suggested by molecular docking studies, indicating their possible mode of action. All things considered, our work shows that thiadiazole-based heterocycles are attractive candidates for the creation of novel antioxidants and anticancer medicines and offers insightful information for future drug design.
Owing to the inert nature and limited mass transfer of gaseous CO2 into the biphasic reaction medium, the direct incorporation of CO2 into complex molecular architectures at ambient temperature and pressure remains a daunting challenge. Here, the study reports a transition metal-free organophotoredox-catalyzed three-component difunctionalization of alkenes that integrates carbamoyl radicals with CO2 fixation under visible light irradiation via a reductive radical-polar crossover (RRPCO) mechanism. Remarkably, oxamic acids serve as bifunctional reagents, and the protocol operates under mild conditions, proceeds under direct sunlight irradiation, and is amenable to 13C labeling, late-stage modification of drugs, and succinimide and diamide scaffold synthesis. Mechanistic investigations and density functional theory calculations support the RRPCO pathway.
Biomaterials have been developed with a great potential in tissue engineering. Hydrogels, especially those based on poly-N-isopropylacrylamide (PNIPAM), have innate mechanical and physicochemical similarities with the native extracellular matrix. We have previously reported the in Vitro compatibility of PNIPAM and its copolymers with a varied number of cell lines, displaying good proliferation rates and bioadhesive capacity. However, the in Vivo biocompatibility assessment is necessary to evaluate. In this work, biocompatibility and immunological acceptance of macroporous hydrogels based on PNIPAM and its co-polymer PNIPAM-co-3%APTA (3-acrylamidopropyl chloride)trimethyl-ammonium) were analyzed using a Wistar female rat model. Hydrogels were synthesized by free radical polymerization and an in Vitro assessment was performed in RAW 264.7 murine macrophages. Then, polymers were implanted subcutaneously and 3-months afterward, grafts were retrieved along with blood and organ samples for haematological, blood chemistry and histological analysis. Cytotoxicity and nitric oxide production did not show variability for the hydrogels. No alterations in the healing process and complete blood count were observed as well as in systemic, liver or kidney toxicity. Histological analysis revealed graft´s integration with the surrounding tissue, without evidence of fibrous capsule or immune cell infiltration. Therefore, these hydrogels are promising biocompatible scaffolds to be used as tissue-engineered constructs.
Harpagophytum procumbens (Burch.) DC., commonly known as devil's claw, is traditionally used in southern Africa for treating inflammatory conditions. Despite its widespread use, comprehensive toxicological and antioxidant evaluations using alternative invertebrate models remain limited. This study investigated the phytochemical composition, acute toxicity, repellent activity, antioxidant capacity, and effects on oxidative stress markers of H. procumbens dry extract (HpDE) using Nauphoeta cinerea as a model organism. HPLC analysis identified six major phenolic compounds: gallic acid, catechin, caffeic acid, rosmarinic acid, rutin, and quercetin. Survival assays using concentrations of 15.625, 31.25, 62.5, 125, and 250 mg/mL demonstrated 100% survival of N. cinerea over 72 h, indicating the absence of acute toxicity in this specific invertebrate model. Behavioral tests revealed concentration-dependent repellent effects at 4 and 8 mg/mL. The DPPH radical scavenging assay showed moderate antioxidant activity with an IC₅₀ of 178.00 mg/mL, approximately 11-fold lower than that of ascorbic acid (IC₅₀ = 16.18 mg/mL). Biochemical analysis demonstrated significant reduction in total free iron levels following treatment with 15.625 and 125 mg/mL HpDE, suggesting modulation of iron homeostasis and potential protective effects against oxidative stress. These findings provide evidence that HpDE exhibits low acute toxicity in N. cinerea while displaying antioxidant properties and iron-modulating activity. The results support the traditional use of H. procumbens and establish N. cinerea as a suitable invertebrate model for preliminary toxicological screening of this botanical extract, although species-specific responses necessitate caution when extrapolating these findings to other organisms.
Momordica charantia L. is a medicinal plant rich in bioactive compounds, including steroidal glycosides, flavonoids, phenolics, triterpenoids, saponins, and polysaccharides, which exhibit antidiabetic, antioxidant, anti-inflammatory, hepatoprotective, and anticancer activities. This review summarizes its nutritional and phytochemical composition, green extraction technologies, molecular mechanisms, and industrial applications based on literature from Google Scholar, PubMed, Scopus, Web of Science, ScienceDirect, and other scientific databases. Ultrasound-assisted extraction is an efficient and eco-friendly method that provides higher recovery of bioactive compounds from M. charantia and improved bioavailability compared with enzyme-assisted, microwave-assisted, and conventional methods. The phytochemicals of M. charantia regulate oxidative stress, inflammation, lipid peroxidation, and glucose homeostasis. Studies show that its antidiabetic effects involve improved insulin sensitivity, enhanced glucose uptake, and inhibition of carbohydrate-digesting enzymes. These compounds also exhibit antioxidant activity through free radical scavenging and anti-inflammatory effects via inhibition of the NF-κB and MAPK pathways. M. charantia further demonstrates anticancer activity by inducing apoptosis, causing cell-cycle arrest, and downregulating proliferation pathways in several cancer cell lines, including MCF-7, HCT-116, HepG2, A549, and PANC-1. Beyond medicinal uses, it is applied in the food industry as a functional ingredient in products such as yogurt, cookies, pickles, bread, juice, oil, and beverages. Overall, M. charantia shows strong potential for therapeutic applications, including functional foods and pharmaceutical formulations targeting diabetes, inflammation, liver diseases, and cancer; however, further studies are needed to confirm its clinical efficacy.
The pineal gland regulates circadian physiology through the periodic production of melatonin (MLT). In addition to its established role as a chronobiotic agent, MLT regulates redox homeostasis and mitochondrial physiology. Mitochondria and redox-active molecules, particularly reactive oxygen species (ROS), play essential roles in reproduction, including gamete physiology, fertilization, and early embryonic development. Although excessive oxidative stress (OS) impairs fertility, controlled ROS signaling is necessary for normal reproductive function. This comprehensive review synthesizes current evidence regarding MLT as a key intermediary linking circadian signaling with mitochondrial physiology and redox homeostasis. We discuss molecular pathways through which MLT regulates mitochondrial function, including activation of the Nrf2 signaling pathway, modulation of mitochondrial permeability transition, regulation of electron transport chain (ETC) efficiency, and apoptotic signaling. Furthermore, this study investigates MLT's ability to scavenge free radicals and activate antioxidant defense mechanisms. Moreover, we review novel findings regarding the effects of MLT in experimental animals and humans, assisted reproductive technologies (ART) such as in vitro fertilization (IVF), and consider the translational significance of the hormone as an enhancer of fertility. We also highlight gaps in the literature, including methodological inconsistencies, supraphysiologic doses, and insufficient data from large human cohorts. Lastly, we discuss an integrative model whereby MLT may function as an important regulator of mitochondrial redox balance, with potential implications for reproductive physiology and reproductive outcomes, and propose new avenues for investigation.
Plant-derived compounds have recently attracted considerable scientific attention due to their potential therapeutic applications, which are largely attributed to their antioxidant properties. Tert-butyl hydroperoxide (t-BHP) is a potent inducer of intracellular oxidative stress, generating reactive free radicals, which significantly contribute to hepatic and renal damage. Micromeria frivaldszkyana (M. frivaldszkyana), a Bulgarian endemic species, contains high levels of phenolic compounds, including linarin, rosmarinic acid (RA), chlorogenic acid, rutin, quercetin, naringenin, and apigenin. In this study, male Wistar rats received oral treatment for 5 days comprising saline, 250, 400, or 500 mg/kg of M. frivaldszkyana methanolic extract, 100 mg/kg RA, or 125 mg/kg silymarin. On the final day, 0.5 mmol/kg of t-BHP was injected intraperitoneally, and blood and liver tissue samples were collected 18 h later for biochemical and histological analysis. Liver and kidney function was evaluated using biochemical markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine (Cr), uric acid (UA)), indicators of oxidative stress (malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT)), and histopathology. Exposure to t-BHP resulted in significant hepatic and renal damage, including elevated serum markers, increased lipid peroxidation, and deoxyribonucleic acid (DNA) damage. Administration of 500 mg/kg M. frivaldszkyana markedly lowered elevated serum ALT and AST levels. The extract also significantly mitigated t-BHP-induced increases in serum Cr and UA. However, no significant increase in the levels of the antioxidant enzymes SOD and CAT or in GSH was observed at all tested doses. Malondialdehyde and 8-OHdG levels increased markedly following t-BHP exposure, whereas pretreatment with M. frivaldszkyana at all tested doses significantly ameliorated these oxidative alterations. These findings suggest that the methanolic extract of M. frivaldszkyana confers protective effects against t-BHP-induced toxicity, potentially through stabilisation of cell membranes, inhibition of lipid peroxidation, and reduction in DNA damage. The extract may therefore serve as a potential natural therapeutic agent against injuries caused by oxidative stress.
Vasodilation is a defence mechanism during inflammation and infection that is regulated by nitric oxide produced by endothelial nitric oxide synthase (eNOS) and the generation of endothelium-dependent hyperpolarization. Several viral infections have been shown to alter vascular biology, but effects of bacterial pathogens are unclear. Here using an ex vivo blood vessel model and human primary endothelial cells, we show that Klebsiella pneumoniae, a prevalent bloodstream pathogen, inhibits vasodilation pathways. The type VI secretion system (T6SS) effector VgrG4 activates the mitochondrial receptor NLRX1, which leads to increased mitochondrial reactive oxygen species and phosphorylation of the eNOS inhibitory site by the kinase PKCβ, which in turn reduces eNOS activity. K. pneumoniae capsule polysaccharide also activates the phosphatase PP2Ac, which reduces phosphorylation of the eNOS activation site. VgrG4-induced mitochondrial reactive oxygen species attenuate endothelium-dependent hyperpolarization by impairing signalling of the Ca2+-activated K+ channel axis. This work reveals that T6SS activity can modulate host vascular biology by targeting eNOS post-translational modifications.
Coreopsis tinctoria Nutt. (commonly known as Kunlun snow chrysanthemum) is a traditional medicinal and edible plant distributed mainly in the high-altitude regions of Xinjiang, China. In traditional medical practices, the dried flower heads (capitula) of C. tinctoria have been widely consumed as an herbal tea for clearing heat, detoxifying, and alleviating inflammatory conditions. In traditional medical theory, the accumulation of "heat and toxins" is closely associated with skin disorders, oxidative damage, and premature aging. However, direct ethnobotanical evidence for its skin-specific or topical use remains limited. Therefore, the present study investigated the skin-protective potential of the dried flower heads of C. tinctoria as an ethnopharmacology-guided extension of its documented heat-clearing, detoxifying, and inflammation-related traditional uses. This study aimed to screen and identify active constituents from the dried flower heads of C. tinctoria and to evaluate their multi-target skin-protective activities related to melanogenesis, oxidative stress, and extracellular-matrix degradation, thereby providing pharmacological evidence for its potential skin-protective applications. A lysozyme-assisted ligand-fishing approach was established by immobilizing tyrosinase, elastase, and hyaluronidase onto lysozyme-modified filter paper to screen potential enzyme inhibitors from the dried flower extract. The isolated compounds were evaluated using α-MSH-induced B16 melanoma cells, UVB-induced HaCaT keratinocytes, and human dermal fibroblasts (HDFs). Western blot analysis, molecular docking, and network pharmacology were used to explore possible mechanisms and structure-related interactions. Fourteen compounds were successfully isolated and identified. In cell-free enzyme assays, quercetagetin-7-O-β-glucoside (2) and okanin (8) showed measurable tyrosinase inhibitory activity, with IC50 values of 78.3 ± 0.0 μM and 66.2 ± 0.4 μM, respectively. Naringenin (12) and luteolin (14) showed elastase inhibitory activity, with IC50 values of 162 μM and 143 μM, respectively. Compound 2 reduced melanin content in the α-MSH-treated B16 cells from 167% to 91.5%, compared to 100% of the untreated normal cells set as control group. Compound 8 exhibited strong radical-scavenging activity (for DPPH· IC50 = 4.23 μM). Several flavonoids also attenuated UVB-induced oxidative-stress-related changes in HaCaT cells and modulated photo-damage-related protein expression in HDFs. The identified multi-target enzyme inhibitors and bioactive flavonoids provide a material basis for the anti-photoaging properties of the flowers of C. tinctoria. These findings support an ethnopharmacology-guided extension of its traditional heat-clearing and detoxifying use into modern skin-protection research, while further studies are required to clarify compound uptake, skin permeability, and in vivo efficacy.
Cirsium boluense P.H.Davis & Parris (Kartal Kangalı) is a local endemic species in Bolu, Türkiye. Members of the Cirsium genus have long been used for cancer, bronchitis, and cough in Anatolia. This study investigated the antimutagenic, antibacterial, and antioxidant properties of methanol extracts obtained from 1st year (leaf and root) and 2nd year (capitulum, stem, leaf, and root) plant materials, along with total phenolic-flavonoid levels and LC-MS/MS profiles. Roots from both growth stages and 2nd year leaves demonstrated the most effective antimutagenic activity, which may be relevant to traditional uses associated with cancer prevention. The 2nd year leaf had the strongest free radical scavenging activity, followed by the capitulum. Leaves showed the highest phenolic-flavonoid content overall. Five bacterial strains were inhibited, with the capitulum showing the most notable antibacterial effect. LC-MS/MS analysis identified apigenin, chlorogenic acid, 1,5-dicaffeoylquinic acid (cynarin), and luteolin as major phenolics in capitulum and leaves. The findings validate traditional medicinal uses and indicate significant pharmacological and nutraceutical potential for C. boluense.
The interaction between medicinal plants and their root-associated microbes plays a key role in shaping rhizosphere chemistry and bioactivity. This study evaluates the antioxidant potential and metabolic profiles of Viola odorata roots and associated Rhizobium sp. BR7 using in vitro DPPH, ABTS, FRAC based antioxidant assays and LC-MS-based untargeted metabolomics. Both plant and microbial extracts exhibited significant free radical-scavenging capacity. The isolate BR7 showed the most potent antioxidant activity (IC50 = 69 µg/mL), followed by AH3, JN9, and SGA9. Isolates BR5 and KB11 showed lower efficacy. The inverse correlation was observed between flavonoid content and ABTS based antioxidant activity, indicating the key role of flavonoids in antioxidant potential. LC-MS based analysis revealed overlapping antioxidant metabolites such as caffeic acid derivatives, kaempferol-3-O46 glucoside, apigenin, and chlorogenic acid, indicating metabolic complementarity between plant and bacteria. Besides these, BR7 also contained unique compounds including indole-3-acetic acid (IAA) fragments, rhamnolipid-like biosurfactants, and alkylresorcinols, suggesting strong rhizosphere adaptability. Overall, Rhizobium sp. BR7 emerges as a promising source of antioxidant co-metabolites with potential applications in biopharmaceutical and functional food development.