Underlying Mechanism Of Action Research Articles

Biocontrol Mechanisms of Three Plant Essential Oils Against Phytophthora infestans Causing Potato Late Blight.

Late blight, caused by the notorious pathogen Phytophthora infestans, poses a significant threat to potato (Solanum tuberosum) crops worldwide, impacting their quality as well as yield. Here, we aimed to investigate the potential use of cinnamaldehyde, carvacrol, and eugenol as control agents against P. infestans and to elucidate their underlying mechanisms of action. To determine the pathogen-inhibiting concentrations of these three plant essential oils (PEOs), a comprehensive evaluation of their effects using gradient dilution, mycelial growth rate, and spore germination methods was carried out. Cinnamaldehyde, carvacrol, and eugenol were capable of significantly inhibiting P. infestans by hindering its mycelial radial growth, zoospore release, and sporangium germination; the median effective inhibitory concentration of the three PEOs was 23.87, 8.66, and 89.65 μl/liter, respectively. Scanning electron microscopy revealed that PEOs caused the irreversible deformation of P. infestans, resulting in hyphal shrinkage, distortion, and breakage. Moreover, propidium iodide staining and extracellular conductivity measurements demonstrated that all three PEOs significantly impaired the integrity and permeability of the pathogen's cell membrane in a time- and dose-dependent manner. In vivo experiments confirmed the dose-dependent efficacy of PEOs in reducing the lesion diameter of potato late blight. Altogether, these findings provide valuable insight into the antifungal mechanisms of PEOs vis-à-vis late blight-causing P. infestans. By utilizing the inherent capabilities of these natural compounds, we could effectively limit the harmful impacts of late blight on potato crops, thereby enhancing agricultural practices and ensuring the resilience of global potato food production.

Therapeutic potential of Buddleja Polystachya Fresen (stem and leaves) extracts: antimicrobial and cytotoxic properties for ocular disease management

This study on Buddleja polystachya highlights its phytochemical composition, antimicrobial activity, and cytotoxic impacts. The study emphasizes the plant’s potential to treat ocular diseases by identifying important compounds involved in the bioactivity through GC-MS analysis. This study explores the antimicrobial and cytotoxic potential of Buddleja polystachya (stem and leaves) extracts, with a focus on their application in treating bacterial ocular infections and their efficacy against MCF7, HT29, and HepG2 cancer cells. Through comprehensive GC-MS analysis, a diverse array of phytochemicals was identified within Buddleja polystachya stem and leaves extracts, including carbohydrates, phenolic derivatives, fatty acids, and steroidal components. The extracts were then evaluated for their biological activities, revealing significant antimicrobial properties against a range of bacterial strains implicated in ocular infections. The research findings demonstrate that stem extracts derived from Buddleja polystachya demonstrated high to moderate cytotoxic effects on cancer cell lines MCF7, HT29, and HepG2. Notably, these effects were characterized by varying IC50 values, which suggest distinct levels of sensitivity. In contrast, leaf extracts exhibited reduced cytotoxicity when tested against all these cell lines, although they did so with a significantly higher cytotoxicity aganist HepG2 cells. The results of this investigation highlight the potential therapeutic utilization of Buddleja polystachya extracts in the management of ocular infections and cancer. These results support the need for additional research to elucidate the underlying mechanisms of action of these extracts and explore their potential as drugs.

Human amniotic membrane modulates collagen production and deposition in vitro

Pathological fibrosis is a significant complication of surgical procedures resulting from the accumulation of excess collagen at the site of repair which can compromise the tissue architecture and severely impede the function of the affected tissue. Few prophylactic treatments exist to counteract this process; however, the use of amniotic membrane allografts has demonstrated promising clinical outcomes. This study aimed to identify the underlying mechanism of action by utilizing relevant models that accurately represent the pathophysiology of the disease state. This study employed a pro-fibrotic in vitro system using TGFβ1 stimulation and macromolecular crowding techniques to evaluate the mechanism by which amniotic membrane allografts regulate collagen biosynthesis and deposition. Following treatment with dehydrated human amnion chorion membrane (DHACM), subsequent RNA sequencing and functional enrichment with Reactome pathway analysis indicated that amniotic membranes are indeed capable of regulating genes associated with the composition and function of the extracellular matrix. Furthermore, macromolecular crowding was used in vitro to expand the evaluation to include both the effects of DHACM and a lyophilized human amnion/chorion membrane (LHACM). DHACM and LHACM regulate the TGFβ pathway and myofibroblast differentiation. Additionally, both DHACM and LHACM modulate the production, secretion, and deposition of collagen type I, a primary target for pathological fibrosis. These observations support the hypothesis that amniotic membranes may interrupt pathological fibrosis by regulating collagen biosynthesis and associated pathways.

E-waste: mechanisms of toxicity and safety testing.

Currently, information on the toxicity profile of the majority of the identified e-waste chemicals, while extensive and growing, is admittedly fragmentary, particularly at the cellular and molecular levels. Furthermore, the toxicity of the chemical mixtures likely to be encountered by humans during and after informal e-waste recycling, as well as their underlying mechanisms of action, is largely unknown. This review paper summarizes state-of-the-art knowledge of the potential underlying toxicity mechanisms associated with e-waste exposures, with a focus on toxic responses connected to specific organs, organ systems, and overall effects on the organism. To overcome the complexities associated with assessing the possible adverse outcomes from exposure to chemicals, a growing number of new approach methodologies have emerged in recent years, with the long-term objective of providing a human-based and animal-free system that is scientifically superior to animal testing, more effective, and acceptable. This encompasses a variety of techniques, typically regarded as alternative approaches for determining chemical-induced toxicities and holds greater promise for a better understanding of key events in the metabolic pathways that mediate known adverse health outcomes in e-waste exposure scenarios. This is crucial to establishing accurate scientific knowledge on mixed e-waste chemical exposures in shorter time frames and with greater efficacy, as well as supporting the need for safe management of hazardous chemicals. The present review paper discusses important gaps in knowledge and shows promising directions for mechanistically anchored effect-based monitoring strategies that will contribute to the advancement of the methods currently used in characterizing and monitoring e-waste-impacted ecosystems.

Nicotinamide riboside restores nicotinamide adenine dinucleotide levels and alleviates brain injury by inhibiting oxidative stress and neuroinflammation in a mouse model of intracerebral hemorrhage.

Hemorrhagic stroke is a global health problem owing to its high morbidity and mortality rates. Nicotinamide riboside is an important precursor of nicotinamide adenine dinucleotide characterized by a high bioavailability, safety profile, and robust effects on many cellular signaling processes. This study aimed to investigate the protective effects of nicotinamide riboside against collagenase-induced hemorrhagic stroke and its underlying mechanisms of action. An intracerebral hemorrhage model was constructed by stereotactically injecting collagenase into the right striatum of adult male Institute for Cancer Research mice. After 30 minutes, nicotinamide riboside was administered via the tail vein. The mice were sacrificed at different time points for assessments. Nicotinamide riboside reduced collagenase-induced hemorrhagic area, significantly reduced cerebral water content and histopathological damage, promoted neurological function recovery, and suppressed reactive oxygen species production and neuroinflammation. Nicotinamide riboside exerts neuroprotective effects against collagenase-induced intracerebral hemorrhage by inhibiting neuroinflammation and oxidative stress.

Nicotinamide riboside restores nicotinamide adenine dinucleotide levels and alleviates brain injury by inhibiting oxidative stress and neuroinflammation in a mouse model of intracerebral hemorrhage.

Hemorrhagic stroke is a global health problem owing to its high morbidity and mortality rates. Nicotinamide riboside is an important precursor of nicotinamide adenine dinucleotide characterized by a high bioavailability, safety profile, and robust effects on many cellular signaling processes. This study aimed to investigate the protective effects of nicotinamide riboside against collagenase-induced hemorrhagic stroke and its underlying mechanisms of action. An intracerebral hemorrhage model was constructed by stereotactically injecting collagenase into the right striatum of adult male Institute for Cancer Research mice. After 30 minutes, nicotinamide riboside was administered via the tail vein. The mice were sacrificed at different time points for assessments. Nicotinamide riboside reduced collagenase-induced hemorrhagic area, significantly reduced cerebral water content and histopathological damage, promoted neurological function recovery, and suppressed reactive oxygen species production and neuroinflammation. Nicotinamide riboside exerts neuroprotective effects against collagenase-induced intracerebral hemorrhage by inhibiting neuroinflammation and oxidative stress.

Advancing understanding of the role of IL-22 in myelination: insights from the Cuprizone mouse model

Despite significant advancements in the field, the pathophysiology of multiple sclerosis (MS) remains partially understood, with limited therapeutic options available for this debilitating condition. The precise impact of Interleukin-22 (IL-22) in the context of MS is still incompletely elucidated with some evidence suggesting its protective role. To provide a more comprehensive understanding of the role of IL-22, we investigated its effect on remyelination in a mouse model of demyelination induced by Cuprizone. Mice underwent a 6 week regimen of Cuprizone or vehicle, followed or not by intraperitoneal administration of IL-22. Behavioral assessments including tail suspension and inverted screen tests were conducted, alongside histological, histochemical, and quantitative PCR analyses. In Cuprizone-treated mice, IL-22 significantly improved motor and behavioral performance and robustly promoted remyelination in the corpus callosum. Additionally, IL-22 administration led to a significant elevation in MBP transcription in brain biopsies of treated mice. These findings collectively suggest a crucial role for IL-22 in the pathophysiology of MS, particularly in supporting the process of remyelination. These results offer potential avenues for expanding therapeutic strategies for MS treatment. Ongoing experiments aim to further unravel the underlying mechanisms of IL-22 action.

Clinical metabolomics investigation of rheumatoid arthritis patients receiving ayurvedic whole system intervention

BackgroundArthritis is a common clinical condition seen in Ayurveda clinics. Clinical trials have reported Ayurvedic interventions to be of benefits in many arthritic conditions including Rheumatoid Arthritis (RA). No mechanistic details however are available about how such interventions on their own or as a combination of whole system Ayurveda might be working. Objective: The study aims to evaluate simultaneously the clinical outcome of Ayurveda whole system (AWS) intervention in RA patients and identifying the serum metabolic signatures which could be useful for diagnosing the disease and monitoring treatment response. Material and methodsRA patients (n = 37) simultaneously diagnosed as Amavata fulfilling the specific inclusion and exclusion criteria were recruited in the study and were given Ayurveda whole system (AWS) intervention comprised of oral medicines, local therapy and dietary recommendation for 3 months. The clinical and serum metabolic changes were investigated for pre-treatment RA patients (baseline RA group, n = 37) and post-treatment RA patients (following treatment of 6-weeks (RA_F, n = 26) and three months (RA_T, n = 36). For comparative serum metabolomics analysis, 57 normal healthy control (HC) subjects were also involved and the serum metabolic profiles were measured at high-field 800 MHz NMR spectrometer. The serum metabolic profiles were compared using multivariate statistical analysis and discriminatory metabolic features were evaluated for diagnostic potential using receiver operating characteristic (ROC) curve analysis. ResultsA significant reduction in DAS-28 ESR, AAM Score, total swollen joints, total tender joints were observed following AWS intervention. The clinical outcomes were concordant with changes in metabolic profiles of RA patients as these were also shifting towards the normal levels following the intervention. Compared to healthy control (HC) subjects, the sera of baseline RA patients were characterised by increased circulatory level of succinate, lysine, mannose, creatine, and 3-Hydroxybutyrate (3-HB) and decreased levels of alanine. The present study also evaluated the serum metabolic ratios for their discriminatory and diagnostic potential and notably, six metabolic ratios (KHR, KThR, KVR, GHR, PTR and SHR) were found significantly altered (elevated) in baseline RA patients. However, in RA patients receiving AWS treatment, these metabolic changes showed marked convergence towards the metabolic signatures of healthy controls. ConclusionThis first of its kind study clearly shows the clinical efficacy of Ayurvedic Whole System (AWS) intervention in the management of Rheumatoid Arthritis (RA), as demonstrated by significant improvements in key clinical parameters. The intervention not only alleviated symptoms but also induced a profound metabolic shifting towards normalization; thus, underscoring the potential of AWS intervention to modulate cellular metabolism in a manner that facilitates a return to homeostasis in RA patients. However, future studies are imperative to confirm these preliminary observations and delineate the underlying mechanisms of action of intervention in cases of RA.

Plasma-activated water: candidate hand disinfectant for SARS-CoV-2 transmission disruption

The global epidemic caused by SARS-CoV-2 has brought about worldwide burden and a sense of danger for more than two years, leading to a wide range of social, public health, economic and environmental issues. Self-inoculation through hands has been the primary way for environmental transmission of SARS-CoV-2. Plasma-activated water (PAW) has been reported as an effective, safe and environmentally friendly disinfectant against SARS-CoV-2. However, the inactivating effect of PAW on SARS-CoV-2 located on skin surface and its underlying mechanism of action have not been elucidated. In this study, PAW was prepared using an air-pressure plasma jet device. The antiviral efficiency of PAW1, PAW3, and PAW5 on the SARS-CoV-2 pseudovirus was 8.20% (±2.88%), 46.24% (±1.79%), and 91.71% (±0.47%), respectively. Additionally, determination of PAW’s physicochemical properties, identification of major sterile effector in PAW, transmission electron microscopy analysis, malondialdehyde (MDA) assessment, SDS-PAGE, ELISA, and qPCR were conducted to reveal the virucidal mechanism of PAW. Our experimental results suggested that peroxynitrite, which was generated by the synergism of acidic environment and reactive species, was the major sterile effector of PAW. Furthermore, we found that PAW treatment significantly inactivated SARS-CoV-2 pseudovirus through the destruction of its structure of and the degradation of the viral RNA. Therefore, the possible mechanism for the structural destruction of SARS-COV-2 by PAW is through the action of peroxynitrite generated by the synergism of acidic environment and reactive species, which might react with and destroy the lipid envelope of SARS-CoV-2 pseudovirus. Nevertheless, further studies are required to shed light on the interaction mechanism of PAW-inherent RONS and viral components, and to confirm the determinant factors for virus inactivation of SARS-COV-2 by PAW. Therefore, PAW may be a candidate hand disinfectant used to disrupt the transmission of SARS-CoV-2.

Plasma-activated water: candidate hand disinfectant for SARS-CoV-2 transmission disruption

The global epidemic caused by SARS-CoV-2 has brought about worldwide burden and a sense of danger for more than two years, leading to a wide range of social, public health, economic and environmental issues. Self-inoculation through hands has been the primary way for environmental transmission of SARS-CoV-2. Plasma-activated water (PAW) has been reported as an effective, safe and environmentally friendly disinfectant against SARS-CoV-2. However, the inactivating effect of PAW on SARS-CoV-2 located on skin surface and its underlying mechanism of action have not been elucidated. In this study, PAW was prepared using an air-pressure plasma jet device. The antiviral efficiency of PAW1, PAW3, and PAW5 on the SARS-CoV-2 pseudovirus was 8.20% (±2.88%), 46.24% (±1.79%), and 91.71% (±0.47%), respectively. Additionally, determination of PAW’s physicochemical properties, identification of major sterile effector in PAW, transmission electron microscopy analysis, malondialdehyde (MDA) assessment, SDS-PAGE, ELISA, and qPCR were conducted to reveal the virucidal mechanism of PAW. Our experimental results suggested that peroxynitrite, which was generated by the synergism of acidic environment and reactive species, was the major sterile effector of PAW. Furthermore, we found that PAW treatment significantly inactivated SARS-CoV-2 pseudovirus through the destruction of its structure of and the degradation of the viral RNA. Therefore, the possible mechanism for the structural destruction of SARS-COV-2 by PAW is through the action of peroxynitrite generated by the synergism of acidic environment and reactive species, which might react with and destroy the lipid envelope of SARS-CoV-2 pseudovirus. Nevertheless, further studies are required to shed light on the interaction mechanism of PAW-inherent RONS and viral components, and to confirm the determinant factors for virus inactivation of SARS-COV-2 by PAW. Therefore, PAW may be a candidate hand disinfectant used to disrupt the transmission of SARS-CoV-2.

Targeting mitochondrial dysfunction in atopic dermatitis with trilinolein: A triacylglycerol from the medicinal plant Cannabis fructus

BackgroundAtopic dermatitis (AD) is a common skin condition that causes chronic and recurring eczema lesions. Prior research has indicated that Cannabis fructus, the mature fruit of Cannabis sativa, has an antioxidant effect. Historically, Cannabis fructus has been used in cosmetics and medicine. However, there is limited knowledge regarding its biological components and the mechanisms by which it prevents and treats AD. ObjectivesHPLC-ESI-MS/MS analysis was utilized to identify the main compounds of Cannabis fructus, and trilinolein was extracted using chromatographic techniques. The potential of trilinolein in the prevention of AD was assessed, and its underlying mechanisms of action were elucidated. MethodsThe distribution of distinct cellular subpopulations and the principal biological processes implicated in the pathogenesis of AD were assessed through a comparative study involving chronic AD patients and healthy controls (HCs). Differential gene expression was validated in clinical samples from the lesions of AD patients and the healthy skin of controls. The pharmacodynamic activity of trilinolein was validated in dinitrochlorobenzene (DNCB)-induced BALB/c mice and in IL-4- and TNF-α-induced HaCaT cells. Proteomics analyse was employed to investigate its mechanisms. ResultsSingle-cell transcriptome analysis revealed that chronic AD is characterized by abnormal keratinocyte differentiation and oxidative stress damage. When topically applied, trilinolein can effectively improve AD-like skin lesions induced by DNCB. It increases the expression of terminal differentiation proteins and decreases the expression of NADPH oxidase 2 (NOX2), with a therapeutic effect comparable to that of the positive control drug crisaborole. Additionally, trilinolein reduced ROS fluorescence intensity, restored mitochondrial morphology and membrane potential, and decreased mitochondrial DNA (mtDNA) release in keratinocytes stimulated with IL-4 and TNF-α. Moreover, trilinolein increased the protein expression of AhR, CYP1A1, and Nrf2 in a dose-dependent manner. The effect of trilinolein on keratinocyte terminal differentiation proteins and ROS levels was blocked by the addition of an AhR inhibitor. ConclusionThe study suggests that trilinolein from Cannabis fructus alleviates NOX2-dependent mitochondrial dysfunction and repair the skin barrier via AhR-Nrf2 pathway, making it a promising agent for the prevention and treatment of AD.

Korean Mint (Agastache rugosa) Extract and Its Bioactive Compound Tilianin Alleviate Muscle Atrophy via the PI3K/Akt/FoxO3 Pathway in C2C12 Myotubes.

Skeletal muscle atrophy, which is characterized by diminished muscle mass, strength, and function, is caused by malnutrition, physical inactivity, aging, and diseases. Korean mint (Agastache rugosa Kuntze) possesses various biological functions, including anti-inflammatory, antioxidant, anticancer, and antiosteoporosis activities. Moreover, it contains tilianin, which is a glycosylated flavone that exerts antioxidant, anti-inflammatory, antidiabetic, and neuroprotective activities. However, no studies have analyzed the inhibitory activity of A. rugosa extract (ARE) and tilianin on muscle atrophy. Thus, the present study investigated the potential of ARE and tilianin on muscle atrophy and their underlying mechanisms of action in C2C12 myotubes treated with tumor necrosis factor-α (TNF-α). The results showed that ARE and tilianin promoted the phosphatidylinositol 3-kinase/protein kinase B pathway, thereby activating mammalian target of rapamycin (a protein anabolism-related factor) and its downstream factors. Moreover, ARE and tilianin inhibited the mRNA expression of muscle RING-finger protein-1 and atrogin-1 (protein catabolism-related factors) by blocking Forkhead box class O3 translocation. ARE and tilianin also mitigated inflammatory responses by downregulating nuclear factor-kappa B expression levels, thereby diminishing the expression levels of inflammatory cytokines, including TNF-α and interleukin-6. Additionally, ARE and tilianin enhanced the expression levels of antioxidant enzymes, including catalase, superoxide dismutase, and glutathione peroxidase. Overall, these results suggest that ARE and tilianin are potential functional ingredients for preventing or improving muscle atrophy.

Evidence of synergistic mechanisms of hepatoprotective botanical herbal preparation of Pueraria montana var. lobata and Schisandra sphenanthera.

Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) and Schisandra sphenanthera Rehder & E.H. Wilson are traditional edible and medicinal hepatoprotective botanical drugs. Studies have shown that the combination of two botanical drugs enhanced the effects of treating acute liver injury (ALI), but the synergistic effect and its action mechanisms remain unclear. This study aimed to investigate the synergistic effect and its mechanism of the combination of Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) (PM) and Schisandra sphenanthera Rehder & E.H. Wilson (SS) in the treatment of ALI. High performance liquid chromatography (HPLC) were utilized to conduct the chemical interaction analysis. Then the synergistic effects of botanical hybrid preparation of PM-SS (BHP PM-SS) against ALI were comprehensively evaluated by the CCl4 induced ALI mice model. Afterwards, symptom-oriented network pharmacology, transcriptomics and metabolomics were applied to reveal the underlying mechanism of action. Finally, the key target genes were experimentally by RT-qPCR. Chemical analysis and pharmacodynamic experiments revealed that BHP PM-SS was superior to the single botanical drug, especially at 2:3 ratio, with a better dissolution rate of active ingredients and synergistic anti-ALI effect. Integrated symptom-oriented network pharmacology combined with transcriptomics and metabolomics analyses showed that the active ingredients of BHP PM-SS could regulate Glutathione metabolism, Pyrimidine metabolism, Arginine biosynthesis and Amino acid sugar and nucleotide sugar metabolism, by acting on the targets of AKT1, TNF, EGFR, JUN, HSP90AA1 and STAT3, which could be responsible for the PI3K-AKT signaling pathway, MAPK signaling pathway and Pathway in cancer to against ALI. Our study has provided compelling evidence for the synergistic effect and its mechanism of the combination of BHP PM-SS, and has contributed to the development and utilization of BHP PM-SS dietary supplements.

Integrating network pharmacology and Mendelian randomization to explore potential targets of matrine against ovarian cancer.

Matrine has been reported inhibitory effects on ovarian cancer (OC) cell progression, development, and apoptosis. However, the molecular targets of matrine against OC and the underlying mechanisms of action remain elusive. This study endeavors to unveil the potential targets of matrine against OC and to explore the intricate relationships between these targets and the pathogenesis of OC. The effects of matrine on the OC cells (A2780 and AKOV3) viability, apoptosis, migration, and invasion was investigated through CCK-8, flow cytometry, wound healing, and Transwell analyses, respectively. Next, Matrine-related targets, OC-related genes, and ribonucleic acid (RNA) sequence data were harnessed from publicly available databases. Differentially expressed analyses, protein-protein interaction (PPI) network, and Venn diagram were involved to unravel the core targets of matrine against OC. Leveraging the GEPIA database, we further validated the expression levels of these core targets between OC cases and controls. Mendelian randomization (MR) study was implemented to delve into potential causal associations between core targets and OC. The AutoDock software was used for molecular docking, and its results were further validated using RT-qPCR in OC cell lines. Matrine reduced the cell viability, migration, invasion and increased the cell apoptosis of A2780 and AKOV3 cells (P< 0.01). A PPI network with 578 interactions among 105 candidate targets was developed. Finally, six core targets (TP53, CCND1, STAT3, LI1B, VEGFA, and CCL2) were derived, among which five core targets (TP53, CCND1, LI1B, VEGFA, and CCL2) differential expressed in OC and control samples were further picked for MR analysis. The results revealed that CCND1 and TP53 were risk factors for OC. Molecular docking analysis demonstrated that matrine had good potential to bind to TP53, CCND1, and IL1B. Moreover, matrine reduced the expression of CCND1 and IL1B while elevating P53 expression in OC cell lines. We identified six matrine-related targets against OC, offering novel insights into the molecular mechanisms underlying the therapeutic effects of matrine against OC. These findings provide valuable guidance for developing more efficient and targeted therapeutic approaches for treating OC.

Protective effects of Amauroderma rugosum on dextran sulfate sodium-induced ulcerative colitis through the regulation of macrophage polarization and suppression of oxidative stress

BackgroundAmauroderma rugosum (AR) is a medicinal mushroom commonly used to treat inflammation, gastric disorders, epilepsy, and cancers due to its remarkable anti-inflammatory and anti-oxidative properties. This study was designed to evaluate the pharmacological effects of AR and its underlying mechanism of action against ulcerative colitis (UC) in vitro and in vivo. MethodsA UC mouse model was established by administration of dextran sulfate sodium (DSS). AR extract was administered intragastrically to mice for 7 days. At the end of the experiment, histopathology, macrophage phenotype, oxidative stress, and inflammatory status were examined in vivo. Furthermore, RAW 264.7, THP-1, and Caco-2 cells were used to elucidate the mechanism of action of AR in vitro. ResultsAR extract (0.5–2 mg/mL) significantly suppressed lipopolysaccharide (LPS) and interferon-gamma (IFN-γ)-induced M1 macrophage (pro-inflammatory) polarization in both RAW 264.7 and THP-1 cells. LPS-induced pro-inflammatory mediators (nitric oxide, TNF-α, IL-1β, MCP-1, and IL-6) were reduced by AR extract in a concentration-dependent manner. Similarly, AR extract downregulated MAPK signaling activity in LPS-stimulated RAW 264.7 cells. AR extract elicited a concentration-dependent increase in the mRNA expression of M2 (anti-inflammatory) phenotype markers (CD206, Arg-1, Fizz-1, and Ym-1) in RAW 264.7 cells. Moreover, AR extract suppressed DSS-induced ROS generation and mitochondrial dysfunction in Caco-2 cells. The in vivo experiment revealed that AR extract (200 mg/kg) increased colon length compared to the DSS-treated group. In addition, disease activity index, spleen ratio, body weight, oxidative stress, and colonic inflammation were markedly improved by AR treatment in DSS-induced UC mice. Finally, AR suppressed M1 and promoted M2 macrophage polarization in UC mice. ConclusionThe AR extract protected against DSS-induced UC by regulating macrophage polarization and suppressing oxidative stress. These valuable findings suggest that adequate intake of AR can prevent and/or treat UC.

Amazonite (A Microcline Feldspar) - An Anti-Cancerous Geo-Biotechnological Approach for H460: Human Lung Cancer with Validation via Ros Anti-Oxidant Analysis

The research delves into the medicinal properties of amazonite, with a particular focus on its potential application in nanomedicine for combating lung cancer. Employing the MTT Assay, the authors observed amazonite's impact on H460 lung cancer cells, revealing its cytotoxic effects and thereby suggesting its promise as an anti-cancer agent. Moreover, through ROS antioxidant analysis, the study unveiled amazonite's ability to regulate reactive oxygen species levels, indicating its potential in mitigating oxidative stress-induced damage, a hallmark of cancer progression. FTIR spectroscopy emerged as a crucial tool in the research, offering insights into amazonite's molecular composition and its possible interactions with biological molecules. Of paramount importance is the toxicity analysis conducted in the study, which revealed amazonite's low toxicity profile. This aspect is particularly significant as it underscores the safety of amazonite for potential therapeutic applications, including in conjunction with treatments like radiotherapy. The assurance of low toxicity is pivotal in ensuring the viability of amazonite as a candidate for clinical use, instilling confidence in its safety profile and minimizing adverse effects on patients. Overall, the findings of the research underscore amazonite's potential as a safe and effective nanomedicine for the treatment of lung cancer. The observed cytotoxic effects on cancer cells, coupled with its ability to modulate reactive oxygen species levels and low toxicity profile, position amazonite as a promising candidate for further exploration in the realm of cancer therapy. However, the study also highlights the need for continued research to fully elucidate the underlying mechanisms of amazonite's action and to explore its potential clinical applications comprehensively.

Unlocking nature’s potential: anticancer potential of Helichrysum sanguineum (L.) Kostel on breast cancer cells and its chemical composition

ABSTRACT Helichrysum sanguineum (L.) Kostel (H. sanguineum), a member of the Asteraceae family, has been traditionally employed for various medicinal purposes owing to its rich phytochemical composition. This study investigates the anticancer properties of various extracts of H. sanguineum (ethanol, acetonitrile, hexane, and chloroform) against breast cancer cells, shedding light on its chemical constituents and their potential therapeutic effects. In vitro assays demonstrate the profound inhibitory effects of H. sanguineum extract on human fibroblast and breast cancer cells. Furthermore, we elucidate the underlying mechanisms of action, revealing its ability to induce apoptosis and cell cycle arrest in breast cancer cells. The cytotoxicity and apoptosis outcomes in breast cancer cells varied across different extracts, yet no adverse effects were observed on healthy cells at equivalent concentrations. Furthermore, all extracts initially promoted breast cancer cell proliferation, with the chloroform extract notably reducing cancer cell proliferation even at low concentrations. GC-MS analysis identifies the major chemical constituents of the extract, including flavonoids, terpenoids, and phenolic compounds, which likely contribute to its anticancer activity. Our findings highlight the potential of H. sanguineum extract as a natural agent for breast cancer treatment and the need for further exploration of its mechanisms and clinical applications.

Exploring the therapeutic potential of achyranthes aspera: A comprehensive review

Achyranthes aspera, commonly known as "Prickly Chaff Flower," is a medicinal plant extensively used in traditional medicine systems worldwide. This review provides a comprehensive overview of the phytochemical constituents, pharmacological properties, and therapeutic potential of Achyranthes aspera. The phytochemical analysis reveals the presence of various bioactive compounds such as alkaloids, flavonoids, saponins, and terpenoids, among others, which contribute to its medicinal properties. Pharmacological studies have demonstrated the diverse therapeutic effects of Achyranthes aspera, including anti-inflammatory, analgesic, antioxidant, antimicrobial, antidiabetic, hepatoprotective, and anticancer activities. Furthermore, the plant has been utilized in the management of various ailments such as arthritis, diabetes, respiratory disorders, gastrointestinal disorders, and skin diseases. However, despite its promising therapeutic potential, further research is warranted to elucidate the underlying mechanisms of action and evaluate its safety and efficacy for clinical applications. This review aims to consolidate the existing knowledge on Achyranthes aspera, providing insights for future research and potential development of novel therapeutic agents.

Cellular mechanisms mediating the anti-cancer effects of carnosol on gingiva carcinoma

Carnosol, a rosemary polyphenol, displays anticancer properties and is suggested as a safer alternative to conventional surgery, radiotherapy, and chemotherapy. Given that its effects on gingiva carcinoma have not yet been investigated, the aim of this study was to explore its anti-tumor selectivity and to unravel its underlying mechanisms of action. Hence, oral tongue and gingiva carcinoma cell lines exposed to carnosol were analyzed to estimate cytotoxicity, cell viability, cell proliferation, and colony formation potential as compared with those of normal cells. Key cell cycle and apoptotic markers were also measured. Finally, cell migration, oxidative stress, and crucial cell signaling pathways were assessed. Selective anti-gingiva carcinoma activity was disclosed. Overall, carnosol mediated colony formation and proliferation suppression in addition to cytotoxicity induction. Cell cycle arrest was highlighted by the disruption of the c-myc oncogene/p53 tumor suppressor balance. Carnosol also increased apoptosis, oxidative stress, and antioxidant activity. On a larger scale, the alteration of cell cycle and apoptotic profiles was also demonstrated by QPCR array. This was most likely achieved by controlling the STAT5, ERK1/2, p38, and NF-ĸB signaling pathways. Lastly, carnosol reduced inflammation and invasion ability by modulating IL-6 and MMP9/TIMP-1 axes. This study establishes a robust foundation, urging extensive inquiry both in vivo and in clinical settings, to substantiate the efficacy of carnosol in managing gingiva carcinoma.

Multi-targeted effects of D-carvone against Non-Small Cell Lung Cancer (NSCLC): A network pharmacology-based study

Non-small cell lung cancer (NSCLC) is a complex malignancy with a high degree of heterogeneity, representing approximately 85% of all lung cancer cases. The treatment landscape for NSCLC has been revolutionised by incorporating targeted and immunotherapies; however, novel therapeutic modalities are consistently needed to enhance the treatment outcomes. Indeed, alternative anti-cancer therapies involving natural products have drawn the attention of clinicians and scientists owing to their remarkable chemopreventive potential, often displaying minimal toxicity. D-carvone (CN) is one such natural product that has exhibited numerous promising therapeutic benefits, yet its efficacy against NSCLC remains enigmatic. In the present study, network pharmacological studies and molecular docking in conjunction with in-vitro validation were used to elucidate the underlying mechanism of action of CN comprehensively. Different databases revealed a total of 77 putative anti-NSCLC targets of CN. The identified core targets were utilised to construct a “Compound- Target- Disease” network by Cytoscape (v3.9.0). Further analysis identified 5 core/ hub targets of CN including JAK2, ERK1, ESR1, GSK3B and HSP90AA1. Molecular docking indicated a strong binding interaction of the compound with these core targets. Also, Gene Ontology and KEGG analysis validated the involvement of multiple biological processes. Additionally, CN significantly inhibited cell proliferation, clonogenicity, and wound healing potential while promoting apoptosis in a dose-dependent manner in H1299 and A549 cell lines as examined by flow cytometry, morphological assessment, and western blotting. In conclusion, this study delineates the therapeutic effects of CN on NSCLC, thus highlighting CN as a putative drug candidate for further analysis.