[Inhibitory effect of 5-hydroxy-6,7-dimethoxyflavone on H1N1 influenza virus-induced ferroptosis and inflammation in A549 cells and its possible mechanisms].

OBJECTIVE: To investigate the protective effect of 5-hydroxy-6,7-dimethoxyflavone (5-HDF), a compound extracted from Elsholtzia blanda Benth., against lung injury induced by H1N1 influenza virus and explore its possible mechanism of action. METHODS: 5-HDF was extracted from Elsholtzia blanda Benth. using ethanol reflux extraction and silica gel chromatography and characterized using NMR and MS analyses. In an A549 cell model of H1N1 influenza virus infection (MOI=0.1), the cytotoxicity of 5-HDF was assessed using MTT assay, and its effect on TRAIL and IL-8 expressions was examined using flow cytometry; Western blotting was used to detect the expression levels of inflammatory, apoptosis, and ferroptosis-related proteins. In a mouse model of H1N1 influenza virus infection established by nasal instillation of 50 µL H1N1 virus at the median lethal dose, the effects of 30 and 60 mg/kg 5-HDF by gavage on body weight, lung index, gross lung anatomy and lung histopathology were observed. RESULTS: 5-HDF exhibited no significant cytotoxicity in A549 cells within the concentration range of 0-200 µg/mL. In H1N1-infected A549 cells, treatment with 5-HDF effectively inhibited the activation of phospho-p38 MAPK and phospho-NF-κB p65, lowered the expressions of IL-8, enhanced the expression of anti-ferroptosis proteins (SLC7A11 and GPX4), and inhibited the expressions of apoptosis markers PARP and caspase-3 and the apoptotic factor TRAIL. In H1N1-infected mice, treatment with 5-HDF for 7 days significantly suppressed body weight loss and increment of lung index and obviously alleviated lung tissue pathologies. CONCLUSION: 5-HDF offers protection against H1N1 influenza virus infection in mice possibly by suppressing H1N1-induced ferroptosis, inflammatory responses, and apoptosis via upregulating SLC7A11 and GPX4, inhibiting the activation of phospho-NF-κB p65 and phospho-p38 MAPK, and decreasing the expression of cleaved caspase3 and cleaved PARP.

Anti-inflammatory and antiarthritic properties of Marrubium vulgare aqueous extract in an animal model.

This study aimed to investigate the potential anti-inflammatory properties of aqueous extract of Marrubium vulgare (AEMV) using various animal models. Several inflammatory models including xylene-induced ear edoema, carrageenan-induced paw edoema, and Freund's adjuvant-induced arthritis were employed to evaluate the anti-inflammatory effects of AEMV. LC-MS/MS of AEMV revealed that the major component was Marrubiin, a diterpenoid lactone. AEMV demonstrated significant anti-inflammatory effects in all animal models tested. It effectively reduced ear and paw edoema induced by xylene and carrageenan, respectively. Furthermore, AEMV attenuated arthritis symptoms and hyperalgesia in rats with Freund's adjuvant-induced arthritis. Biochemical analyzes revealed normalisation of inflammatory markers, including C-reactive protein (CRP) levels, in treated animals. The findings suggest that AEMV possesses promising anti-inflammatory properties, supporting its potential therapeutic application in inflammatory conditions such as arthritis. Further investigations are needed to clarify the underlying mechanisms and optimise dosing regimens for clinical use.

Egg white hydrolysate peptides act as antimicrobial and anti-inflammatory agents for acne.

A simple method to generate antibacterial peptides by alkaline hydrolysis of hen egg whites is reported. The method reproducibly generates short peptides with molecular weight of less than 14.4 kDa that exhibit low to no cytotoxicity on RAW 264.7 macrophage cells, but do inhibit the bacterial growth of Cutibacterium acnes (C. acnes), Staphylococcus aureus (S. aureus) and antibiotic-resistant S. aureus (MRSA), while also reducing nitric oxide production from heat-killed C. acnes-treated RAW 264.7 cells. Peptidomics revealed at least thirty peptides within the complex mixture, of which eight were evaluated individually. Three peptides (PK8, EE9 and RP8) were potent anti-inflammation and antibacterial agents, but notably the complex egg white hydrolysate (EWH) was more effective than the individual peptides. Electron microscopy suggests the antibacterial mechanism of both the hydrolysate and the selected peptides is through disruption of the cell membrane of C. acnes. These findings suggest that EWH and EWH-derived peptides are promising candidates for infection and inflammation treatment, particularly in managing acne and combating antibiotic-resistant bacteria like MRSA.

An updated review of the pharmacological effects and potential mechanisms of hederagenin and its derivatives.

Hederagenin (HG) is a natural pentacyclic triterpenoid that can be isolated from various medicinal herbs. By modifying the structure of HG, multiple derivatives with superior biological activities and safety profiles have been designed and synthesized. Accumulating evidence has demonstrated that HG and its derivatives display multiple pharmacological activities against cancers, inflammatory diseases, infectious diseases, metabolic diseases, fibrotic diseases, cerebrovascular and neurodegenerative diseases, and depression. Previous studies have confirmed that HG and its derivatives combat cancer by exerting cytotoxicity, inhibiting proliferation, inducing apoptosis, modulating autophagy, and reversing chemotherapy resistance in cancer cells, and the action targets involved mainly include STAT3, Aurora B, KIF7, PI3K/AKT, NF-κB, Nrf2/ARE, Drp1, and P-gp. In addition, HG and its derivatives antagonize inflammation through inhibiting the production and release of pro-inflammatory cytokines and inflammatory mediators by regulating inflammation-related pathways and targets, such as NF-κB, MAPK, JAK2/STAT3, Keap1-Nrf2/HO-1, and LncRNA A33/Axin2/ß-catenin. Moreover, anti-pathogen, anti-metabolic disorder, anti-fibrosis, neuroprotection, and anti-depression mechanisms of HG and its derivatives have been partially elucidated. The diverse pharmacological properties of HG and its derivatives hold significant implications for future research and development of new drugs derived from HG, which can lead to improved effectiveness and safety profiles.

A study on the antioxidant, anti-inflammatory, and xanthine oxidase inhibitory activity of the Artemisia vulgaris L. extract and its fractions.

ETHNOPHARMACOLOGICAL RELEVANCE: Vietnamese people use mugwort (Artemisia vulgaris L.) to treat arthritis and gout. Our previous research shows that mugwort contains flavonoids, and its extract possesses antibacterial and anti-inflammatory activities. However, no publications have been on the xanthine oxidase inhibitory activity of mugwort and acute anti-inflammatory activity in vivo. AIM OF THE STUDY: The study aimed to verify the antioxidant, xanthine oxidase inhibitory, and anti-inflammatory capabilities of mugwort extract in vitro and in vivo, isolate phyto-compounds from potential bioactive fractions, and then evaluate their potential in inhibiting xanthine oxidase. METHODS: According to established methods, the extract and the active flavonoids were obtained using different chromatographic techniques. DPPH, ABTS, reducing power, and H2O2 elimination were used to evaluate antioxidant activity. The model of LPS-induced RAW264.7 cells was used to measure the inhibition of NO production. The carrageenan-induced paw oedema model was used to assess acute inflammation in mice. In vitro, xanthine oxidase inhibition assay was applied to investigate the effects of extract/compounds on uric acid production. Chemical structures were identified by spectral analysis. RESULTS: The assessment of the acute inflammatory model in mice revealed that both the 96% ethanol and the 50% ethanol extracts significantly decreased oedema in the mice's feet following carrageenan-induced inflammation. 96% ethanol extract exhibited a better reduction in oedema at the low dose. The analysis revealed that the ethyl acetate fraction had the highest levels of total polyphenols and flavonoids. Additionally, this fraction demonstrated significant antioxidant activity in various assays, such as DPPH, ABTS, reducing power, and H2O2 removal. Furthermore, it displayed the most potent inhibition of xanthine oxidase, an anti-inflammatory activity. Five phytochemicals were isolated and determined from the active fraction such as luteolin (1), rutin (2), apigenin (3), myricetin (4), and quercetin (5). Except for rutin, the other compounds demonstrated the ability to inhibit effective xanthine oxidase compared to standard (allopurinol). Moreover, quercetin (5) inhibited NO production (IC50 21.87 µM). CONCLUSION: The results indicate that extracts from A. vulgaris effectively suppressed the activity of xanthine oxidase and exhibited antioxidant and anti-inflammatory properties, potentially leading to a reduction in the production of uric acid in the body and eliminating ROS. The study identified mugwort extract and bioactive compounds derived from Artemisia vulgaris, specifically luteolin, apigenin, and quercetin, as promising xanthine oxidase inhibitors. These findings suggest that further development of these compounds is warranted. At the same time, the above results also strengthen the use of mugwort to treat gout disease in Vietnam.

The roles and potential mechanisms of plant polysaccharides in liver diseases: a review.

Plant polysaccharides (PP) demonstrate a diverse array of biological and pharmacological properties. This comprehensive review aims to compile and present the multifaceted roles and underlying mechanisms of plant polysaccharides in various liver diseases. These diseases include non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), fibrosis, drug-induced liver injury (DILI), and hepatocellular carcinoma (HCC). This study aims to elucidate the intricate mechanisms and therapeutic potential of plant polysaccharides, shedding light on their significance and potential applications in the management and potential prevention of these liver conditions. An exhaustive literature search was conducted for this study, utilizing prominent databases such as PubMed, Web of Science, and CNKI. The search criteria focused on the formula "(plant polysaccharides liver disease) NOT (review)" was employed to ensure the inclusion of original research articles up to the year 2023. Relevant literature was extracted and analyzed from these databases. Plant polysaccharides exhibit promising pharmacological properties, particularly in the regulation of glucose and lipid metabolism and their anti-inflammatory and immunomodulatory effects. The ongoing progress of studies on the molecular mechanisms associated with polysaccharides will offer novel therapeutic strategies for the treatment of chronic liver diseases (CLDs).

IL-1ra loaded chondroitin sulfate-functionalized microspheres for minimally invasive treatment of intervertebral disc degeneration.

Presently, the clinical treatment of intervertebral disc degeneration (IVDD) remains challenging, but the strategy of simultaneously overcoming the overactive inflammation and restoring the anabolic/catabolic balance of the extracellular matrix (ECM) in the nucleus pulposus (NP) has become an effective way to alleviate IVDD. IL-1ra, a natural antagonist against IL-1ß, can mitigate inflammation and promote regeneration in IVDD. Chondroitin sulfate (CS), an important component of the NP, can promote ECM synthesis and delay IVDD. Thus, these were chosen and integrated into functionalized microspheres to achieve their synergistic effects. First, CS-functionalized microspheres (GelMA-CS) with porous microstructure, good monodispersion, and about 200 µm diameter were efficiently and productively fabricated using microfluidic technology. After lyophilization, the microspheres with good local injection and tissue retention served as the loading platform for IL-1ra and achieved sustained release. In in vitro experiments, the IL-1ra-loaded microspheres exhibited good cytocompatibility and efficacy in inhibiting the inflammatory response of NP cells induced by lipopolysaccharide (LPS) and promoting the secretion of ECM. In in vivo experiments, the microspheres showed good histocompatibility, and local, minimally invasive injection of the IL-1ra-loaded microspheres could reduce inflammation, maintain the height of the intervertebral disc (IVD) and the water content of NP close to about 70% in the sham group, and retain the integrated IVD structure. In summary, the GelMA-CS microspheres served as an effective loading platform for IL-1ra, eliminated inflammation through the controlled release of IL-1ra, and promoted ECM synthesis via CS to delay IVDD, thereby providing a promising intervention strategy for IVDD. STATEMENT OF SIGNIFICANCE: The strategy of simultaneously overcoming the overactive inflammation and restoring the anabolic/catabolic balance of the extracellular matrix (ECM) in nucleus pulposus (NP) has shown great potential prospects for alleviating intervertebral disc degeneration (IVDD). From the perspective of clinical translation, this study developed chondroitin sulfate functionalized microspheres to act as the effective delivery platform of IL-1ra, a natural antagonist of interleukin-1ß. The IL-1ra loading microspheres (GelMA-CS-IL-1ra) showed good biocompatibility, good injection with tissue retention, and synergistic effects of inhibiting the inflammatory response induced by lipopolysaccharide and promoting the secretion of ECM in NPCs. In vivo, they also showed the beneficial effect of reducing the inflammatory response, maintaining the height of the intervertebral disc and the water content of the NP, and preserving the integrity of the intervertebral disc structure after only one injection. All demonstrated that the GelMA-CS-IL-1ra microspheres would have great promise for the minimally invasive treatment of IVDD.

Therapeutic potential of Capparis spinosa in experimental model of acute acetic acid-induced colitis: Anti-inflammatory and antioxidant effects.

Introduction: This study examined the anti-inflammatory and antioxidant properties of Capparis spinosa L. (caper) in order to determine its medicinal potential in the treatment of acute colitis. Method: Sixty male rats were divided into six groups. After the experimental period, distal colonic extension was collected for determination of colonic damage, oxidative stress markers, along with antioxidant markers. The impact of altered levels of inflammatory cytokines in colon tissues on the underlying mechanisms examined. Results: The results showed that administering different doses of caper led to significant decreases in TNF-α and IL-6 levels when compared to the control colitis group (p < 0.001). Caper treatment effectively lowered elevated oxidative stress factors (MDA, NO, and MPO) compared to the control colitis group (p < 0.001). Caper treatment resulted in a significant increase in antioxidant factors (CAT, SOD, and GSH) compared with the control colitis group (p < 0.001).Significant improvements in tissue repair were observed in caper-treated groups compared to positives and control colitis (p < 0.001). Conclusion: The study highlights caper may be useful in the treatment of acute colitis due to its ameliorative effects on inflammation, oxidative stress, and tissue repair.

2-(3-(Chloromethyl)benzoyloxy)benzoic Acid Reduces Prostaglandin E-2 Concentration, NOX2 and NFKB Expression, ROS Production, and COX-2 Expression in Lipopolysaccharide-Induced Mice.

INTRODUCTION: Inflammation is a fundamental response to various insults, including microbial invasion and tissue injury. While aspirin (ASA) has been widely used for its anti-inflammatory properties, its adverse effects and limitations highlight the need for novel therapeutic alternatives. Recently, a novel salicylic acid derivative, 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid (3-CH2Cl), has emerged as a potential substitute for ASA, offering a simpler, environmentally friendly synthesis and a promising safety profile. AIM OF THE STUDY: This research aims to evaluate the anti-inflammatory mechanism of 3-CH2Cl in a lipopolysaccharide (LPS)-induced mouse model, focusing on its effects on prostaglandin E-2 (PGE-2) concentration, NOX2 and NFkB expression, ROS production, and COX-2 expression. MATERIAL AND METHODS: Utilizing BALB/C mice subjected to LPS-induced inflammation, we investigated the therapeutic potential of 3-CH2Cl. The study included synthesis and tablet preparation, experimental design, peripheral blood plasma PGE-2 measurement, splenocyte isolation and COX-2 expression analysis, nitric oxide and ROS measurement, and immunohistochemical analysis of NOX2 and NFkB expression. RESULTS: 3-CH2Cl significantly reduced PGE-2 levels (p=0.005), NO concentration in liver homogenates (p=0.005) and plasma (p=0.0011), and expression of NOX2 and NFkB in liver (p<0.0001) and splenocytes (p=0.0036), demonstrating superior anti-inflammatory activity compared to ASA. Additionally, it showed potential in decreasing COX-2 expression in splenocytes. CONCLUSION: 3-CH2Cl exhibits potent anti-inflammatory properties, outperforming ASA in several key inflammatory markers in an LPS-induced inflammation model. The reduction of COX-2 expression, alongside the reduction of pro-inflammatory cytokines and oxidative stress markers, suggest it as a promising therapeutic agent for various inflammatory conditions.

Efficacy of Rhamnus utilis Decne. Aqueous extract in mice with acute alcoholic liver injury and metabolomic study.

Rhamnus utilis Decne. (Family Rhamnaceae Juss.) leaf is commonly prepared as a anti-inflammatory herbal medicine and used for tea production. To investigate the mechanism of Rhamnus utilis Decne. aqueous extract (RDAE) against acute alcoholic liver disease (ALD) in mice. The ALD mouse (Male ICR) model was induced via intragastric administration of 52 % alcohol. Mice in each group were treated by gavage once daily with the RDAE (1.12, 2.25, 4.500 g/kg). The expression of proteins involved in the MAPKs/NF-κB/COX-2-iNOS pathway was measured by western blotting. Non-targeted metabolomics was used to determine metabolic profiles and critical pathways, while targeted metabolomics validated key amino acid metabolites. After administration of RDAE, the body mass of mice was significantly increased. The liver index was significantly decreased. Meanwhile, the serum levels of AST, ALT, TG, TC, MDA, TNF-α, IL-1ß and IL-6 were significantly decreased (P < 0.05, P < 0.01), but GSH level was inversely increased (P < 0.05). Metabolomic analysis revealed nine major pathways involved in the therapeutic effect of RDAE, including fructose and mannose metabolism. The levels of 7 amino acids including leucine, proline and alanine/sarcosine were significantly upregulated. Additionally, protein levels of p-NF-κB (p65)/NF-κB (p65), p-ERK1/2/ERK1/2, p-JNK/JNK, p-p38/p38, COX-2 and iNOS were significantly decreased (P < 0.01, P < 0.05). RDAE is used to treat acute ALD by improving lipid metabolism, inhibiting the expression of pro-inflammatory cytokines and regulating MAPKs/NF-κB/COX-2-iNOS signalling pathway. These findings provide valuable insights for acute ALD therapy based on traditional Chinese medicine (TCM).

Oral Intake of Linseed Oil Inhibits Skin Barrier Dysfunction in Obese Mice.

OBJECTIVE: Obesity is not only a risk factor for lifestyle-related diseases but also causes skin barrier dysfunction, which leads to a reduced quality of life due to dryness, itching, and scratching, and thus requires appropriate treatment. However, there are no studies on this issue. Therefore, this study aimed to examine whether oral intake of linseed oil is effective for skin barrier function in obesity and to confirm how the effect is demonstrated. METHODS: TSOD mice received either sterile distilled water (Control group) or linseed oil (Omega group), containing a high level of omega-3 fatty acids, including α-linolenic acid, orally for eight weeks. Mice were then irradiated with ultraviolet B (UVB) and three days later, transepidermal water loss (TEWL), which is the primary outcome of skin barrier function, was measured and gross skin appearance was observed. Hematoxylin and eosin (HE) staining and Ki-67 immunostaining were performed on skin samples. mRNA expression levels of the inflammatory markers Tnfα, Cox2, Mcp1, and Hmox1 were measured by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). We also performed fatty acid analysis of skin and erythrocytes by gas chromatography. Statistical analysis was performed using unpaired Student's t-test and Pearson's correlation analysis. RESULTS: Compared with the Control group, the Omega group exhibited lower TEWL values and little skin erythema. Histological analysis revealed thinner epidermis and fewer Ki-67 positive cells. Additionally, in the Omega group, mRNA levels of four inflammation-related genes were lower, α-linolenic acid levels in both skin and erythrocytes were higher, and a lower n-6/n-3 ratio was observed. And α-linolenic acid levels in the skin were negatively correlated with the expression levels of inflammation-related genes. CONCLUSION: Oral intake of linseed oil was found to inhibit skin barrier dysfunction in obesity. This effect was mediated by α-linolenic acid, a major component of linseed oil with anti-inflammatory properties, which was taken up by erythrocytes and supplied to the skin. Therefore, oral intake of linseed oil is expected to be a useful therapeutic method for skin barrier dysfunction in obesity.

Paravertebrally-Injected Multifunctional Hydrogel for Sustained Anti-Inflammation and Pain Relief in Lumbar Disc Herniation.

Pain caused by lumbar disc herniation (LDH) severely compromises patients' quality of life. The combination of steroid and local anesthetics is routinely employed in clinics to alleviate LDH-induced pain. However, the approach only mediates transient efficacy and requires repeated and invasive lumbar epidural injections. Here a paravertebrally-injected multifunctional hydrogel that can efficiently co-load and controlled release glucocorticoid betamethasone and anesthetics ropivacaine for sustained anti-inflammation, reactive oxygen species (ROS)-removal and pain relief in LDH is presented. Betamethasone is conjugated to hyaluronic acid (HA) via ROS-responsive crosslinker to form amphiphilic polymer that self-assemble into particles with ropivacaine loaded into the core. Solution of drug-loaded particles and thermo-sensitive polymer rapidly forms therapeutic hydrogel in situ upon injection next to the herniated disc, thus avoiding invasive epidural injection. In a rat model of LDH, multifunctional hydrogel maintains the local drug concentration 72 times longer than free drugs and more effectively inhibits the expression of pro-inflammatory cytokines and pain-related molecules including cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). Therapeutic hydrogel suppresses the LDH-induced pain in rats for 12 days while the equivalent dose of free drugs is only effective for 3 days. This platform is also applicable to ameliorate pain caused by other spine-related diseases.

Resveratrol as an Anti-inflammatory Agent in Coronary Artery Disease: A Systematic Review, Meta-Analysis and Meta-Regression.

BACKGROUND: Resveratrol is a non-flavonoid polyphenol that shows promise in reducing pro-inflammatory factors and maintaining endothelial function, which hints at its potential role in slowing atherosclerosis and preventing acute coronary events. OBJECTIVE: To study the cardioprotective effects of resveratrol on inflammatory mediators and endothelial function in patients with coronary artery disease (CAD). METHODS: A thorough search was conducted in databases (Cochrane Library, ProQuest, PubMed, LILACS, ScienceDirect, Springer, Taylor&Francis, CNKI, Wanfang, and Weipu) until September 24, 2023. The vasopro-inflammatory mediators, endothelial function and outcomes related to cardiovascular events were observed. Titles and abstracts were assessed, and bias was evaluated with Cochrane RoB 2.0. Heterogeneity of results was explored by meta-regression, certainty of evidence was assessed by the GRADE system, and conclusive evidence was enhanced by trial sequence analysis. RESULTS: Ten randomized controlled trials and 3 animal studies investigated resveratrol's impact on inflammatory mediators and endothelial function. In primary prevention studies, meta-analysis showed a significant reduction (95% CI: -0.73 to -0.20; P=0.0005) in tumor necrosis factor-α (TNF-α) expression with resveratrol, demonstrating a dose-dependent relationship. No significant difference was observed in interleukin-6 (IL-6) expression with P=0.58 for primary prevention and P=0.57 for secondary prevention. Vascular endothelial nitric oxide synthase (eNOS) expression was significantly increased after resveratrol pre-treatment following CAD events. Secondary prevention studies yielded no significant results; however, meta-regression identified associations between age, hypertension, and lower doses with the extent of TNF-α alterations. High certainty of evidence supported TNF-α reduction, while evidence for IL-6 reduction and eNOS elevation was deemed low. CONCLUSION: Resveratrol reduces TNF-α in individuals at risk for CAD, specifically 15 mg per day. However, its usefulness in patients with confirmed CAD is limited due to factors such as age, high blood pressure, and insufficient dosage. Due to the small sample size, the reduction of IL-6 is inconclusive. Animal studies suggest that resveratrol enhances endothelial function by increasing eNOS. (PROSPERO registration No. CRD42023465234).

Surface Passivation of Carbon Dots for Tunable Biological Performance.

Recent investigations were shifted this trend toward exploring the biomedical applicability of CDs, relevant to chronic diseases. Herein, a systematic approach is demonstrated for studying the effect of variation in the surface passivation of CDs for tuning its optical character and biological performance. Alginate and pectin were successfully clustered oxygen-surface passivated CDs, while, chitin was used to nucleate nitrogen-surface passivated CDs. Pectin-treated with base (4.1 ± 1.8 nm) and chitin-treated acid (3.5 ± 1.7 nm) were ingrained the smallest O-surface passivated CDs and N-surface passivated CDs, respectively. However, N-surface passivated CDs were shown with the highest optical activity. CDs colloids prepared from alginate, pectin & chitin, resulted in reduction of tumor cell viability percentage to be 80.8%, 74.0% & 69.0% respectively. O-surface passivated CDs nucleated from alginate showed the highest anti-proliferative effects. Moreover, O-surface passivated CDs (from alginate) showed the supremacy in inhibition of inflammation, while, increasing of its concentration ten times resulted in significant increment in inhibition percent to be 28% & 42%, using 1 µg/mL & 10 µg/mL, respectively. In summarization, it could be decided that, compared to N-surface passivated CDs (from chitin), O-surface passivated CDs (from alginate) showed excellency in application as a concurrent anti-inflammatory/antitumor drug, to be applied as a potential therapeutical reagent for treatment of inflammation, in production of vaccines, immune-therapeutics, and immune-suppressive drugs.

Extraction of kaempferol derivatives from Zygophyllum paulayanum and its diverse biological activities.

Zygophyllum paulayanum (Zygophyllaceae), is a plant commonly found in the desert region, well-known for its antioxidant, anticancer, wound healing, anti-inflammatory and antibacterial, properties. In this present work, we have studied the extraction of kaempferol derivatives from Z. paulayanum which showed excellent biological activities. The whole plant (root, leaves and stem) was extracted using ethanol, hydrolysed with HCl, and studied for the identification of active molecules. Different techniques like TLC, HPLC, and LCMS have been used to identify and confirm the kaempferol aglycone flavonoid. A mass spectrometric method based on electrospray ionisation has confirmed the presence of kaempferol flavonoid. Apart from the hydrolysed extract, the unhydrolyzed extract was also tested for LCMS which confirms the presence of glycosides such as kaempferol 3-O-beta-D-glucopyranosyl-7-O-alpha-L-rhamnopyranoside, kaempferol 3-O-ß -rutinoside and kaempferol-3-o-rhamnoside. Both extracts of Z. paulayanum exhibited superior antioxidant, anti-inflammatory, antimicrobial, phytoestrogenic and cytotoxic properties which might be due to the presence of kaempferol derivatives.

Nitrogen-doped carbon dots derived from ellagic acid and L-tyrosine for photothermal anticancer and anti-inflammation.

Photothermal therapy (PTT) of tumor would ineluctably cause oxidative stress and related inflammation in adjacent normal tissues, leading to a discounted therapeutic outcome. To address this issue, herein an innovative therapeutic strategy that integrates photothermal anticancer and normal cell protection is developed. A new type of nitrogen-doped carbon dot (ET-CD) has been synthesized in one step by hydrothermal method using ellagic acid and L-tyrosine as reaction precursors. The as-prepared ET-CD exhibits high photothermal conversion efficiency and good photothermal stability. After intravenous injection, ET-CD can accumulate at the tumor site and the hyperthermia generated under near infrared laser irradiation effectively ablates tumor tissues, thereby significantly inhibiting tumor growth. Importantly, owing to the inherited antioxidant activity from ellagic acid, ET-CD can remove reactive oxygen and nitrogen species produced in the body and reduce the levels of inflammatory factors induced by oxidative stress, so as to alleviate the damage caused by heat-induced inflammation to normal cells and tissues while photothermal anticancer. These attractive features of ET-CD may open the exploration of innovative therapeutic strategies to promote the clinical application of PTT.

Emodin alleviates intestinal ischemia-reperfusion injury through antioxidant stress, anti-inflammatory responses and anti-apoptosis effects via Akt-mediated HO-1 upregulation.

BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury is a severe vascular emergency. Previous research indicated the protective effects of Emodin on I/R injury. Our study aims to explore the effect of Emodin on intestinal I/R (II/R) injury and elucidate the underlying mechanisms. METHODS: C57BL/6 mice and Caco-2 cells were used for in vivo and in vitro studies. We established an animal model of II/R injury by temporarily occluding superior mesenteric artery. We constructed an oxygen-glucose deprivation/reoxygenation (OGD/R) cell model using a hypoxia-reoxygenation incubator. Different doses of Emodin were explored to determine the optimal therapeutic dose. Additionally, inhibitors targeting the protein kinase B (Akt) or Heme oxygenase-1 (HO-1) were administered to investigate their potential protective mechanisms. RESULTS: Our results demonstrated that in animal experiments, Emodin mitigated barrier disruption, minimized inflammation, reduced oxidative stress, and inhibited apoptosis. When Akt or HO-1 was inhibited, the protective effect of Emodin was eliminated. Inhibiting Akt also reduced the level of HO-1. In cell experiments, Emodin reduced inflammation and apoptosis in the OGD/R cell model. Additionally, when Akt or HO-1 was inhibited, the protective effect of Emodin was weakened. CONCLUSIONS: Our findings suggest that Emodin may protect the intestine against II/R injury through the Akt/HO-1 signaling pathway.

Phytocosmetic potential of Blumea balsamifera oil in mitigating UV-induced photoaging: Evidence from cellular and mouse models.

ETHNOPHARMACOLOGICAL RELEVANCE: Blumea balsamifera (L.) DC. (BB), the source of Blumea balsamifera oil (BBO), is an aromatic medicinal plant, renowned for its pharmacological properties and its traditional use in Southeast Asian countries such as China, Thailand, Vietnam, Malaysia, and the Philippines for centuries. Traditionally, BB has been used as a raw herbal medicine for treating various skin conditions like eczema, dermatitis, athlete's foot, and wound healing for skin injuries. AIM OF THE STUDY: This research aimed to explore the inhibitory effects of BBO on skin aging using two models: in vitro analysis with human dermal fibroblasts (HDF) under UVB-induced stress, and in vivo studies on UVA-induced dorsal skin aging in mice. The study sought to uncover the mechanisms behind BBO's anti-aging effects, specifically, its impact on cellular and tissue responses to UV-induced skin aging. MATERIALS AND METHODS: We applied doses of 10-20 µL/mL of BBO to HDF cells that had been exposed to UVB radiation to simulate skin aging. We measured cell viability, and levels of reactive oxygen species (ROS), SA-ß-gal, pro-inflammatory cytokines, and matrix metalloproteinases (MMPs). In addition, we investigated the involvement of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathways in mediating the anti-aging effects of BBO. Histopathological and biochemical analyses were conducted in a mouse model to examine the effects of BBO on UV-induced photoaging. RESULTS: UV exposure accelerated aging, and caused cellular damage and inflammatory responses through ROS-mediated pathways. In HDF cells, BBO treatment countered the UVB-induced senescence, and the recovery of cell viability was correlated to notable reductions in SA-ß-gal, ROS, pro-inflammatory cytokines, and MMPs. Mechanistically, the anti-aging effect of BBO was associated with the downregulation of the JNK/NF-κB signaling pathways. In the in vivo mouse model, BBO exhibited protective capabilities against UV-induced photoaging, which were manifested by the enhanced antioxidant enzyme activities and tissue remodeling. CONCLUSIONS: BBO effectively protects fibroblasts from UV-induced photoaging through the JNK/NF-κB pathway. Recovery from photoaging involves an increase in dermal fibroblasts, alleviation of inflammation, accelerated synthesis of antioxidant enzymes, and slowed degradation of ECM proteins. Overall, BBO enhances the skin's defensive capabilities against oxidative stress, underscoring its potential as a therapeutic agent for oxidative stress-related skin aging.

Coordinating Macrophage Targeting and Antioxidation by Injectable Nanocomposite Hydrogel for Enhanced Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA), an immune-mediated inflammatory disease, is characterized by a large number of infiltrated immune cells and abnormally elevated reactive oxygen species (ROS) in the joint. Various proinflammatory factors secreted by macrophages and the elevated ROS by inflammatory cells are deeply intertwined and together contribute to joint damage. Targeted and sustained anti-inflammation and antioxidation strategies are needed for RA treatment. To alleviate the oxidative stress and target the source of inflammatory cytokines, we developed a thermosensitive injectable hydrogel, Dex-DSLip/Cro@Gel, to coordinate the targeted anti-inflammatory and antioxidation effects. Within the injectable gel, dexamethasone (Dex)-loaded liposomes (Dex-DSLip), modified with dextran sulfate (DS), target macrophages via interaction with scavenger receptor A (SR-A). Simultaneously, crocin I (Cro) is loaded in the gel with a high loading capacity. The porous structure of Dex-DSLip/Cro@Gel successfully prolongs the retention time of both drugs and sustains the release of Dex and Cro. After intra-articular injection of Dex-DSLip/Cro@Gel in RA rats, the expression of inflammatory factors in the ankle joints was significantly reduced. Joint erythema and bone erosion were markedly alleviated. Through the synergistic effects of Dex and Cro, Dex-DSLip/Cro@Gel demonstrates targeted anti-inflammatory and antioxidation effects as well as mitigated bone erosion and long-term therapeutic effects for RA. This thermosensitive injectable nanocomposite hydrogel synergizes anti-inflammatory and antioxidation effects and targets the microenvironment in the joint, offering a new approach for RA treatment.

Integrating network pharmacology and experimental verification to reveal the anti-inflammatory ingredients and molecular mechanism of pycnogenol.

Introduction: Pycnogenol (PYC), a standardized extract from French maritime pine, has traditionally been used to treat inflammation. However, its primary active components and their mechanisms of action have not yet been determined. Methods: This study employed UPLC-MS/MS (Ultra-high performance liquid chromatography-tandem mass spectrometry) and network pharmacology to identify the potential active components of PYC and elucidate their anti-inflammatory mechanisms by cell experiments. Results: 768 PYC compounds were identified and 19 anti-inflammatory compounds were screened with 85 target proteins directly involved in the inflammation. PPI (protein-protein interaction) analysis identified IL6, TNF, MMP9, IL1B, AKT1, IFNG, CXCL8, NFKB1, CCL2, IL10, and PTGS2 as core targets. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis suggested that the compound in PYC might exert anti-inflammatory effects through the IL17 and TNF signal pathways. Cell experiments determined that PYC treatment can reduce the expression of IL6 and IL1ß to relieve inflammation in LPS (lipopolysaccharide)-induced BV2 cells. Conclusion: PYC could affect inflammation via multi-components, -targets, and -mechanisms.