Search Results (2,853)

Chilean Schinus molle has been used in traditional medicine for effects such as antibacterial, antifungal, anti-inflammatory, analgesic, antiviral, antitumoral, antioxidant, antispasmodic, astringent, antipyretic, cicatrizant, cytotoxic, diuretic, among others. In this study, we evaluated the pharmacological potential of Schinus molle seed essential oil extract (SM_EO) through in vitro and in silico approaches. In vitro, the antioxidant potential was analyzed, and antitumor activity was evaluated in non-tumor and human epithelial tumor cell lines. Caenorhabditis elegans was used as a model for evaluating toxicity, and the chemical composition of the SM_EO was analyzed using gas chromatography–mass spectrometry. The oil contained four major monoterpenes: α-phellandrene (34%), β-myrcene (23%), limonene (13%), and β-phellandrene (7%). Based on quantum mechanical calculations, the reactivity of the molecules present in the SM_EO was estimated. The results indicated that α- phellandrene, β-phellandrene, and β-myrcene showed the highest nucleophilic activity. In addition, the compounds following these as candidates for antioxidant and antiproliferative activities were α-phellandrene, β-phellandrene, ρ-cymene, sabinene, caryophyllene, l-limonene, and α-pinene, highlighting β-myrcene. Based on ADME-Tox properties, it is feasible to use these compounds as new drug candidates. Moreover, the antibacterial activity MIC value obtained for B. cereus was equivalent to 2 μg/mL, and for Y. enterocolitica, S. enteritidis, and S. typhimurium, the MIC value was 32.5 μg/μL. SM_EO could selectively inhibit the proliferation of human epithelial mammary tumor MCF7 cells treated with SM_EOs at 64 and 16 ug/mL—a significant increase in BCL-2 in a dose-dependent manner—and showed low toxicity against Caenorhabditis elegans (from 10 to 0.078 mg·mL⁻¹). These findings suggest that SM_EO may be a potential source of bioactive compounds, encouraging further investigation for applications in veterinary medicine, cosmetics, and sanitation. Full article

Acute Respiratory Distress Syndrome (ARDS) is a complex and devastating form of respiratory failure, with high mortality rates, for which there is no pharmacological treatment. The acute exudative phase of ARDS is characterized by severe damage to the alveolar–capillary barrier, infiltration of protein-rich fluid into the lungs, neutrophil recruitment, and high levels of inflammatory mediators. Rapid resolution of this reversible acute phase, with efficient restoration of alveolar functional integrity, is essential before the establishment of irreversible fibrosis and respiratory failure. Several lines of in vitro and in vivo evidence support the involvement of potassium (K⁺) channels—particularly KvLQT1, expressed in alveolar cells—in key cellular mechanisms for ARDS resolution, by promoting alveolar fluid clearance and epithelial repair processes. The aim of our study was to investigate whether pharmacological activation of KvLQT1 channels could elicit beneficial effects on ARDS parameters in an animal model of acute lung injury. We used the well-established bleomycin model, which mimics (at day 7) the key features of the exudative phase of ARDS. Our data demonstrate that treatments with the KvLQT1 activator R-L3, delivered to the lungs, failed to improve endothelial permeability and lung edema in bleomycin mice. However, KvLQT1 activation significantly reduced neutrophil recruitment and tended to decrease levels of pro-inflammatory cytokines/chemokines in bronchoalveolar lavages after bleomycin administration. Importantly, R-L3 treatment was associated with significantly lower injury scores, higher levels of alveolar type I (HTI-56, AQP5) and II (pro-SPC) cell markers, and improved alveolar epithelial repair capacity in the presence of bleomycin. Together, these results suggest that the KvLQT1 K⁺ channel may be a potential target for the resolution of the acute phase of ARDS. Full article

Essential oils (EOs) constitute intricate mixtures of volatile phytochemicals that have garnered significant attention due to their multifaceted biological effects. Notably, the presence of bioactive constituents capable of inhibiting tyrosinase enzyme activity and scavenging reactive oxygen species (ROS) underpins their potential utility in skin-related applications, particularly through the modulation of melanin biosynthesis and protection of skin-relevant cells from oxidative damage—a primary contributor to hyperpigmentation disorders. Zingiber officinale Rosc. (ginger) and Humulus lupulus L. (hop) are medicinal plants widely recognized for their diverse pharmacological properties. To the best of our knowledge, this study provides the first report on the synergistic interactions between essential oils derived from these species (referred to as EOZ and EOH) offering novel insights into their combined bioactivity. The purpose of this study was to evaluate essential oils extracted from ginger rhizomes and hop strobiles with respect to the following: (1) chemical composition, determined by gas chromatography–mass spectrometry (GC-MS); (2) tyrosinase inhibitory activity; (3) capacity to inhibit linoleic acid peroxidation; (4) ABTS^•+ radical scavenging potential. Furthermore, the study utilizes both the combination index (CI) and dose reduction index (DRI) as quantitative parameters to evaluate the nature of interactions and the dose-sparing efficacy of essential oil (EO) combinations. GC–MS analysis identified EOZ as a zingiberene-rich chemotype, containing abundant sesquiterpene hydrocarbons such as α-zingiberene, β-bisabolene, and α-curcumene, while EOH exhibited a caryophyllene diol/cubenol-type profile, dominated by oxygenated sesquiterpenes including β-caryophyllene-9,10-diol and 1-epi-cubenol. In vitro tests demonstrated that both oils, individually and in combination, showed notable anti-tyrosinase, radical scavenging, and lipid peroxidation inhibitory effects. These results support their multifunctional bioactivity profiles with possible relevance to skin care formulations, warranting further investigation. Full article

Virgin coconut oil (VCO) has emerged as a functional food oil with considerable health benefits and wide applications in the food, pharmaceutical, and cosmetic industries due to its resident bioactive compounds, including lauric acid (LA). LA is the most abundant saturated medium-chain fatty acid in VCO and has been associated with several pharmacological activities. The literatures show the pharmacological effects of VCO and LA on chronic pathologies, infectious diseases, and metabolic disorders. A robust body of evidence shows that LA and other phenolic compounds are responsible for the VCO protection against toxicities and pharmacological efficacies. This review elucidates the anticancer mechanisms of VCO/LA and their modulation of the chemotherapy-induced side effect toxicity. VCO, LA, and their nanomaterial/encapsulated derivatives promote ROS generation, antiproliferation, apoptosis, cell cycle arrest, the inhibition of metastasis, and the modulation of cancer-related signaling pathways for cancer cell death in vivo and in vitro. VCO mitigates oxidative inflammation and apoptosis to block the underlying mechanisms of the side effect toxicity of chemotherapy. However, the possible beneficial effect of LA on the toxicity of chemotherapy is currently unknown. The available evidence emphasizes the anticancer effect and mechanism of VCO and LA, and the VCO potential to combat adverse side effects of chemotherapy. Thus, VCO and LA are potential adjuvant therapeutic agents in the management of various cancers. Nevertheless, future studies should be targeted at elucidating cancer-related molecular mechanisms to bridge the gap in knowledge. Full article

The MIM1-BH3 mimetic, which inhibits the Mcl-1 antiapoptotic protein, may be an efficacious molecule able to induce apoptosis. Previously, we found that moxifloxacin (MXFL) is able to modulate Mcl-1 protein expression. Therefore, in the current study, we assessed the impact of the MXFL, MIM1, and MXFL/MIM1 mixtures on viability and apoptosis in amelanotic A375 and melanotic G361 melanoma cells. The obtained results showed that MXFL and MIM1 exerted high cytotoxic and proapoptotic potential. In the case of two-component models, we have demonstrated that the use of the MIM1 and MXFL mixtures resulted in a significant intensification of both cytotoxic and proapoptotic activity, shown as a modulatory effect on the early and late phases of apoptosis toward the analyzed melanoma cells when compared with MIM1 or MXFL alone. We report, for the first time, the high proapoptotic activity of MIM1 and MXFL applied in a two-component model toward melanoma cells, pointing to the Mcl-1 protein as an important molecular target. The observed potential synergistic mode of action—expressed as cytotoxic and proapoptotic activity enhancement, detected for MIM1 and MXFL—may represent a new direction for further in vitro and in vivo experiments concerning the role of the Mcl-1 protein in the treatment of melanoma. Moreover, the presented results certainly contribute to expanding the knowledge of the pharmacology of both fluoroquinolones and BH3 mimetics, and also enable a better understanding of melanoma cell biology. Full article

Allicin (ALC), a naturally occurring organosulfur compound derived from garlic (Allium sativum), exhibits potential neuroprotective properties. Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by degeneration of dopaminergic neurons and motor dysfunction. This study utilized bioinformatics and network pharmacology methods to predict the anti-PD mechanism of ALC and established in vivo and in vitro PD models using 6-hydroxydopamine (6-OHDA) for experimental verification. Network pharmacological analysis indicates that apoptosis regulation and the PKA/p-CREB/BDNF signaling pathway are closely related to the anti-PD effect of ALC, and protein kinase A (PKA) and dopamine transporter (DAT) are key molecular targets. The experimental results show that ALC administration can alleviate the cytotoxicity of SH-SY5Y induced by 6-OHDA and simultaneously improve the motor dysfunction and dopaminergic neuron loss in PD mice. In addition, ALC can also activate the PKA/p-CREB/BDNF signaling pathway and increase the DAT level in brain tissue, regulate the expression of BAX and Bcl-2, and reduce neuronal apoptosis. These results indicate that ALC can exert anti-PD effects by up-regulating the PKA/p-CREB/BDNF/DAT signaling pathway and inhibiting neuronal apoptosis, providing theoretical support for the application of ALC in PD. Full article

Ischemic stroke is a serious disease that frequently occurs in the elderly and is characterized by a complex pathophysiology and a limited number of effective therapeutic agents. Salvianolic acid A (SAL-A) is a natural product derived from the rhizome of Salvia miltiorrhiza, which possesses diverse pharmacological activities. This study aims to investigate the effect and mechanisms of SAL-A in inhibiting ferroptosis to improve ischemic stroke. Brain injury, oxidative stress and ferroptosis-related analysis were performed to evaluate the effect of SAL-A on ischemic stroke in photochemical induction of stroke (PTS) in mice. Lipid peroxidation levels, antioxidant protein levels, tissue iron content, nuclear factor erythroid 2-related factor 2 (Nrf2), and mitochondrial morphology changes were detected to explore its mechanism. SAL-A significantly attenuated brain injury, reduced malondialdehyde (MDA) and long-chain acyl-CoA synthase 4 (ACSL4) levels. In addition, SAL-A also amplified the antioxidative properties of glutathione (GSH) when under glutathione peroxidase 4 (GPX4), and the reduction in ferrous ion levels. In vitro, brain microvascular endothelial cells (b.End.3) exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) were used to investigate whether the anti-stroke mechanism of SAL-A is related to Nrf2. Following OGD/R, ML385 (Nrf2 inhibitor) prevents SAL-A from inhibiting oxidative stress, ferroptosis, and mitochondrial dysfunction in b.End.3 cells. In conclusion, SAL-A inhibits ferroptosis to ameliorate ischemic brain injury, and this effect is mediated through Nrf2. Full article

Background: Hepatocellular carcinoma (HCC) is one of the most common and fatal malignancies worldwide, characterized by remarkable molecular heterogeneity and poor clinical outcomes. Despite advancements in diagnosis and treatment, the prognosis for HCC remains dismal, largely due to late-stage diagnosis and limited therapeutic efficacy. Therefore, there is a critical need to identify novel therapeutic targets and explore alternative strategies, such as drug repurposing, to improve patient outcomes. Methods: In this study, we employed network pharmacology, molecular docking, and molecular dynamics (MD) simulations to explore the potential therapeutic targets of Nirmatrelvir in HCC. Results: Nirmatrelvir targets were predicted through SwissTarget (101 targets), SuperPred (1111 targets), and Way2Drug (38 targets). Concurrently, HCC-associated genes (5726) were retrieved from DisGeNet. Cross-referencing the two datasets identified 29 overlapping proteins. A protein–protein interaction (PPI) network constructed from the overlapping proteins was analyzed using CytoHubba, identifying 10 hub genes, with HDAC1, HDAC3, and STAT3 achieving the highest degree scores. Molecular docking revealed a strong binding affinity of Nirmatrelvir to HDAC1 (docking score = −7.319 kcal/mol), HDAC3 (−6.026 kcal/mol), and STAT3 (−6.304 kcal/mol). Moreover, Nirmatrelvir displayed stable dynamic behavior in repeated 200 ns simulation analyses. Binding free energy calculations using MM/GBSA showed values of −23.692 kcal/mol for the HDAC1–Nirmatrelvir complex, −33.360 kcal/mol for HDAC3, and −21.167 kcal/mol for STAT3. MM/PBSA analysis yielded −17.987 kcal/mol for HDAC1, −27.767 kcal/mol for HDAC3, and −16.986 kcal/mol for STAT3. Conclusions: The findings demonstrate Nirmatrelvir’s strong binding affinity towards HDAC3, underscoring its potential for future drug development. Collectively, the data provide computational evidence for repurposing Nirmatrelvir as a multi-target inhibitor in HCC therapy, warranting in vitro and in vivo studies to confirm its clinical efficacy and safety and elucidate its mechanisms of action in HCC. Full article

Idiopathic pulmonary fibrosis (IPF) is characterized by excessive extracellular matrix (ECM) deposition driven by aberrant fibroblast-to-myofibroblast transition (FMT). However, the upstream regulators and downstream effectors of this process remain incompletely understood. Here, we identify acyl-CoA synthetase long-chain family member 4 (ACSL4), a lipid metabolic enzyme, as a critical mediator linking complement component 5a (C5a)/C5a receptor 1 (C5aR1) signaling to FMT via calcium signaling. In bleomycin (BLM)-induced pulmonary fibrosis of C57BL/6JGpt mice, and in C5a-stimulated primary lung fibroblasts, the expression of ACSL4 was markedly upregulated. Pharmacological inhibition of ACSL4 (PRGL493) or C5aR1 (PMX53) attenuated the deposition of ECM and suppressed the expression of fibrotic markers in vivo and in vitro. Mechanistically, the activation of C5a/C5aR1 signaling increased intracellular calcium levels and promoted the expression of ACSL4, while inhibition of calcium signaling (FK506) reversed the upregulation of ACSL4 and FMT-related changes, including the expression of α-smooth muscle actin (αSMA) and the migration of fibroblasts. Notably, inhibition of ACSL4 did not affect the proliferation of fibroblasts, suggesting its specific role in phenotypic transition. These findings demonstrate that ACSL4 functions downstream of C5a/C5aR1-induced calcium signaling to promote FMT and the progression of pulmonary fibrosis. Targeting ACSL4 may therefore offer a novel therapeutic strategy for IPF. Full article

Murine microglia exhibit rapid self-renewal upon removal from the postnatal brain. However, the signaling pathways that regulate microglial repopulation remain largely unclear. To address this knowledge gap, we depleted microglia from mixed glial cultures using anti-CD11b magnetic particles and cultured them for 4 weeks to monitor their repopulation ability in vitro. Flow cytometry and immunocytochemistry revealed that anti-CD11b bead treatment effectively eliminated >95% of microglia in mixed glial cultures. Following removal, the number of CX3CR1-positive microglia gradually increased; when a specific threshold was reached, repopulation ceased without any discernable rise in cell death. Cell cycle and 5-ethynyl-2′-deoxyuridine incorporation assays suggested the active proliferation of repopulating microglia at d7. Time-lapse imaging demonstrated post-removal division of microglia. Colony-stimulating factor 1 receptor-phosphoinositide 3-kinase-protein kinase B signaling was identified as crucial for microglial repopulation, as pharmacological inhibition or neutralization of the pathway significantly abrogated repopulation. Transwell cocultures revealed that resident microglia competitively inhibited microglial proliferation probably through contact inhibition. This in vitro microglial removal system provides valuable insights into the mechanisms underlying microglial proliferation. Full article

The thalamus is an important sensory relay station. It integrates all somatic sensory pathways (excluding olfaction) and transmits information through thalamic relay neurons before projecting to the cerebral cortex via thalamocortical axons (TCAs). Emerging evidence has shown that FGF3, a member of the morphogen family, is an axon guidance molecule that repels TCAs away from the hypothalamus and into the internal capsule so that they subsequently reach different regions of the cortex. However, current studies on FGF-mediated axon guidance predominantly focus on phenomenological observations, with limited exploration of the underlying molecular mechanisms. To address this gap, we investigated both direct and indirect downstream signaling pathways mediating FGF3-dependent chemorepulsion of TCAs at later developmental stages. Firstly, we used pharmacological inhibitors to identify the signaling cascade(s) responsible for FGF3-triggered direct chemorepulsion of TCAs, in vitro and in vivo. Our results demonstrate that the PC-PLC pathway is required for FGF3 to directly stimulate the asymmetrical repellent growth of developing TCAs. Then, we found the FGF3-mediated repulsion can be indirectly induced by Slit1 because the addition of FGF3 in the culture media induced an increase in Slit1 expression in the diencephalon. Furthermore, by using downstream inhibitors, we found that the indirect repulsive effect of FGF3 is mediated through the PI3K downstream pathway of FGFR1. Full article

Moringa oleifera (MO), a nutritionally and pharmacologically potent species, is emerging as a sustainable candidate for applications across bioenergy, agriculture, textiles, pharmaceuticals, and biomedicine. This review explores recent advances in MO-based biotechnologies, highlighting novel extraction methods, green nanotechnology, and clinical trial findings. Although MO’s resilience offers promise for climate-smart agriculture and public health, challenges remain in standardizing cultivation and verifying therapeutic claims. This work underscores MO’s translational potential and the need for integrative, interdisciplinary research. MO is used in advanced materials, like electrospun fibers and biopolymers, showing filtration, antibacterial, anti-inflammatory, and antioxidant properties—important for the biomedical industry and environmental remediation. In textiles, it serves as an eco-friendly alternative for wastewater treatment and yarn sizing. Biotechnological advancements, such as genome sequencing and in vitro culture, enhance traits and metabolite production. MO supports green biotechnology through sustainable agriculture, nanomaterials, and biocomposites. MO shows potential for disease management, immune support, metabolic health, and dental care, but requires further clinical trials for validation. Its resilience is suitable for land restoration and food security in arid areas. AI and deep learning enhance Moringa breeding, allowing for faster, cost-effective development of improved varieties. MO’s diverse applications establish it as a key element for sustainable development in arid regions. Full article

Some studies performed in our laboratory on pyrrole and its derivatives pointed towards the enrichment of the evaluations of these promising chemical structures for the potential treatment of neurodegenerative conditions in general and Parkinson’s disease in particular. A classical Paal-Knorr cyclization approach is applied to synthesize the basic hydrazine used for the formation of the designed series of hydrazones (15a–15g). The potential neurotoxic and neuroprotective effects of the newly synthesized derivatives were investigated in vitro using different models of induced oxidative stress at three subcellular levels (rat brain synaptosomes, mitochondria, and microsomes). The results identified as the least neurotoxic molecules, 15a, 15d, and 15f applied at a concentration of 100 µM to the isolated fractions. In addition, the highest statistically significant neuroprotection was observed for 15a and 15d at a concentration of 100 µM using three different injury models on subcellular fractions, including 6-hydroxydopamine in rat brain synaptosomes, tert-butyl hydroperoxide in brain mitochondria, and non-enzyme-induced lipid peroxidation in brain microsomes. The hMAOA/MAOB inhibitory activity of the new compounds was studied at a concentration of 1 µM. The lack of a statistically significant hMAOA inhibitory effect was observed for all tested compounds, except for 15f, which showed 40% inhibitory activity. The most prominent statistically significant hMAOB inhibitory effect was determined for 15a, 15d, and 15f, comparable to that of selegiline. The corresponding selectivity index defined 15f as a non-selective MAO inhibitor and all other new hydrazones as selective hMAOB inhibitors, with 15d indicating the highest selectivity index of >471. The most active and least toxic representative (15d) was evaluated in vivo on Rotenone based model of Parkinson’s disease. The results revealed no microscopically visible alterations in the ganglion and glial cells in the animals treated with rotenone in combination with 15d. Full article

The fungal component of microbiota, known as the mycobiome, inhabits different body niches such as the skin and the gastrointestinal, respiratory, and genitourinary tracts. Much information has been gained on the bacterial component of the human microbiota, but the mycobiome has remained somewhat elusive due to its sparsity, variability, susceptibility to environmental factors (e.g., early life colonization, diet, or pharmacological treatments), and the specific in vitro culture challenges. Functionally, the mycobiome is known to play a role in modulating innate and adaptive immune responses by interacting with microorganisms and immune cells. The latter elicits anti-fungal responses via the recognition of specific fungal cell-wall components (e.g., β-1,3-glucan, mannan, and chitin) by immune system receptors. These receptors then regulate the activation and differentiation of many innate and adaptive immune cells including mucocutaneous cell barriers, macrophages, neutrophils, dendritic cells, natural killer cells, innate-like lymphoid cells, and T and B lymphocytes. Mycobiome disruptions have been correlated with various diseases affecting mostly the brain, lungs, liver and pancreas. This work reviews our current knowledge on the mycobiome, focusing on its composition, research challenges, conditioning factors, interactions with the bacteriome and the immune system, and the known mycobiome alterations associated with disease. Full article

Resistance of various bacterial pathogens to the activity of clinically approved drugs currently leads to serious infections, rapid spread of difficult-to-treat diseases, and even death. Taking the threats for human health in mind, researchers are focused on the isolation and characterization of novel natural products, including plant secondary metabolites. These molecules serve as inspiration and a suitable structural platform in the design and development of novel semi-synthetic and synthetic derivatives. All considered compounds have to be adequately evaluated in silico, in vitro, and in vivo using relevant approaches. The current review paper briefly focuses on the chemical and metabolic properties of resveratrol (1), as well as its oligomeric structures, viniferins, and viniferin-based molecules. The core scaffolds of these compounds contain so-called privileged structures, which are also present in many clinically approved drugs, indicating that those natural, properly substituted semi-synthetic, and synthetic molecules can provide a notably broad spectrum of beneficial pharmacological activities, including very impressive antimicrobial efficiency. Except for spectral verification of their structures, these compounds suffer from the determination or prediction of other structural and physicochemical characteristics. Therefore, the structure–activity relationships for specific dihydrodimeric and dimeric viniferins, their bioisosteres, and derivatives with notable efficacy in vitro, especially against chosen Gram-positive bacterial strains, are summarized. In addition, a set of descriptors related to their structural, physicochemical, pharmacokinetic, and toxicological properties is generated using various computational tools. The obtained values are compared to those of clinically approved drugs. The particular relationships between these in silico parameters are also explored. Full article