Pro-inflammatory COX-2 Research Articles

Broccoli Byproduct Extracts Attenuate the Expression of UVB-Induced Proinflammatory Cytokines in HaCaT Keratinocytes

Broccoli byproducts are an important source of bioactive compounds, which provide important benefits for human skin due mainly to their antioxidant and anti-inflammatory properties. The primary target of UVB radiation is the basal layer of cells in the epidermis, with keratinocytes being the most abundant cell population in this layer. Given the wide range of side effects caused by exposure to UVB radiation, reducing the amount of UV light that penetrates the skin and strengthening the protective mechanisms of the skin are interesting strategies for the prevention of skin disorders. This work aims to evaluate the protective mechanisms triggered by broccoli by-products extract (BBE) on HaCaT keratinocytes exposed to UVB radiation as well as the study of the regenerative effect of these extracts on the barrier of skin keratinocytes damaged by superficial wounds as a strategy to revalorize this agricultural waste. The results obtained revealed that the BBEs exhibited a high cytoprotective effect on the HaCaT exposed to UVB light, allowing it to effectively reduce the intracellular content of ROS, as well as effectively attenuating the increase in proinflammatory cytokines (IL-1β, IL-6, IL-78, TNF-α) and COX-2 induced by this type of radiation. Furthermore, the BBE could be an excellent regenerative agent for skin wound repair, accelerating the migration capacity of keratinocytes thus contributing to the valorization of this byproduct as a valuable ingredient in cosmetic formulations.

Cinnamaldehyde-Mediated Suppression of MMP-13, COX-2, and IL-6 Through MAPK and NF-κB Signaling Inhibition in Chondrocytes and Synoviocytes Under Inflammatory Conditions

Inflammatory disorders encompass a range of conditions, including osteoarthritis (OA), characterized by the body’s heightened immune response to diverse stimuli. OA is a prevalent degenerative joint disease characterized by the progressive deterioration of joint cartilage and subchondral bone, leading to pain, limited mobility, and physical disability. Synovitis, the inflammation of the synovial membrane, is increasingly recognized as a critical factor in OA pathogenesis and progression. This study evaluates the therapeutic potential of cinnamaldehyde (CA), a bioactive compound derived from cinnamon, on synovial and articular inflammation in OA. Given CA’s established anti-inflammatory, antioxidant, and antibacterial properties, this research explores its specific impact on OA and synovitis. The cytotoxicity of CA was assessed using a CCK-8 assay in human IL-1β pretreated chondrocytes and synoviocytes, which serve as in vitro models of OA and synovitis. The study further examined the effects of CA on the expression of proinflammatory cytokines, including IL-6, COX-2, and TNF-α, utilizing multiple analytical techniques. Additionally, the production of matrix metalloproteinases (MMP-3 and MMP-13) and the activation of the NF-κB signaling pathway, particularly the phosphorylation of p65 (pp65), were investigated. The role of the NF-κB inhibitor 5HPP-33 and its downstream effects on gene expression, including COX-2 and IL-6, as well as the MAPK pathway components (p38, ERK, and JNK), were also explored. An MEK inhibitor (U0126) was employed to assess its downstream impact on COX-2 and IL-6 expressions. The results demonstrated that CA significantly inhibited the expression of proinflammatory cytokines and suppressed NF-κB activation in IL-1β pretreated chondrocytes and synoviocytes. These findings suggest that CA, in a dose-dependent manner, may serve as an effective therapeutic agent for preventing OA and synovitis, offering valuable insights into its potential role in managing synovial inflammation and OA.

Enhanced anti-inflammatory effects and metabolic profiles of cyanidin-3-glucoside via nanoliposomal encapsulation in Caco-2 and RAW 264.7 co-culture system

Cyanidin-3-glucoside (C3G) has been found to prevent/treat intestinal disease and maintain gut homeostasis. Numerous studies have proved that nanoliposomes can improve the absorption and utilization of food nutrients. However, the impacts of C3G nanoliposomes (C3G-NL) are still unkown. This study investigated the effects of cyanidin-3-glucoside nanoliposomes (C3G-NL) on intestinal inflammation and permeability using a Caco-2/RAW264.7 co-culture model. ELISA and qPCR results showed that C3G-NL reduced pro-inflammatory markers, including TNF-α, IL-6, IL-8, cyclooxygenase-2, and inducible nitric oxide synthase, while inhibiting the NF-κB/MAPK pathway. C3G-NL also improved intestinal barrier integrity by increasing transepithelial electrical resistance and upregulating tight junction proteins (zonula occludens-1, occludin, claudin-1). Additionally, C3G-NL enhanced C3G metabolism, leading to the formation of intermediary metabolites like chalcone and dihydroflavonols, which contributed to the synthesis of other anthocyanins (delphinidin, peonidin, petunidin, malvidin, and pelargonidin). Overall, C3G-NL helps mitigate inflammation and restore tight junction integrity via metabolic regulation.

Bioactive phenolics from the bulbs of Hymenocallis littoralis

Hymenocallis littoralis, commonly known as Coastal Spider lily, is a perennial herbaceous plant in the Amaryllidaceae family. It is native to tropical and subtropical regions of the Americas, celebrated for its remarkably beautiful flowers. In this study, five previously undescribed chromones, one new benzopyran, along with five known chromones and fourteen known flavonoids, were identified. Among these, compounds 6, 9, 12, 18, 19, 20, and 22 were natural products isolated from H. littoralis for the first time. Their structures were determined using spectroscopic techniques (NMR and MS). Anti-inflammatory activities of the isolated chromone and benzopyran were evaluated in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophage cells. Compound 11 exhibited significant inhibitory effects on nitric oxide (NO) production with an IC50 value of 38.24 μM. Further investigations revealed that compound 11 exerted its anti-inflammatory activity by preventing the nuclear translocation of NF-κB and down-regulating the expression of pro-inflammatory factors, including iNOS, COX-2, IL-1β, and IL-6, in a concentration-dependent manner. This study provides evidence that benzopyran from H. littoralis may serve as a potential source of an anti-inflammatory agent.

Anticancer activity of EMD37 against human head and neck cancer: Impact on apoptotic and inflammatory machineries

Accumulating evidence emphasizes the tumorigenic role of epidermal growth factor receptor (EGFR) in head and neck cancer (HNC). Although cetuximab is the sole anti-EGFR approved by the Food and Drug Administration for treating HNC patients.its response rates are modest. Thus, novel effective and tolerable therapeutic strategies are urged. We previously reported the capability of oxadiazole derivatives to degrade tyrosine kinase receptors including EGFR and exhibit potent anticancer activities against NCI-60 panel which does not include HNC. The aim of this study was to investigate the potential anticancer activity of EMD37, a novel 1,2,4-oxadiazole derivative, against human HNC cells and if effective, to examine the effect of EMD37 on apoptotic and inflammation mediators. Indeed, EMD37 exhibited potent cytotoxicity against patient-derived HNC cell lines (HNO-97, HN-9 and FaDu). Delving deeper, EMD37 triggered intrinsic and extrinsic apoptosis in HNC cells as evidenced by increased levels of caspase-8, caspase-9, caspase-3, caspase-7, caspase-6, TP53BP1 tumor suppressor and Bax, and downregulated anti-apoptotic Bcl-2 protein. EMD37 also significantly abrogated the levels of pro-inflammatory interleukin-1β, interleukin-6, cyclooxygenase-2 and matrix metalloproteinases (MMP-2 and MMP-9) which are heightened in HNC. Bioinformatic analysis revealed that BCL2low, IL6low and MMP9low HNC biospecimens are enriched with epithelial cell differentiation gene set, and CASP8high cohort is enriched with extrinsic apoptosis. Altogether, this study emphasizes the therapeutic potential of targeting the apoptotic and inflammatory machineries in HNC using EMD37.

Anti-inflammatory activity of Ziziphus jujuba hydroalcoholic extract in acetic acid-induced ulcerative colitis model.

Ulcerative colitis (UC) is a common gastrointestinal (GI) disorder characterized by chronic inflammation. Current treatments primarily focus on symptom management, but they have inherent limitations. Global attention is increasingly directed towards exploring herbal remedies as complementary approaches. This study aims to investigate the effects of the hydroalcoholic extract of jujuba on an experimental model of ulcerative colitis. In this study, 15 male BALB/c mice were divided into three experimental groups. The first group served as the untreated UC model, acting as the positive control (PC). The second group received treatment with the hydroalcoholic extract of Ziziphus jujuba, while the third group was treated with mesalamine. UC was induced by injecting 100 μL of 4 % acetic acid (AA) intra-rectally several times. Treatment commenced after the onset of symptoms such as diarrhea and bloody stools. The mice were eventually euthanized ethically, and their spleen and intestinal tissues were collected for analysis. Evaluations included the Disease Activity Index (DAI), myeloperoxidase activity (MPO), nitric oxide (NO) levels, cytokine levels (IL-1β, IL-6, TNF-α), and gene expression (iNOS, COX-2, and cytokines). The hydroalcoholic extract of the jujuba plant significantly reduced MPO, NO, the DAI, and the production and expression of inflammatory cytokines, as well as the genes iNOS and COX-2, in the group receiving this extract compared to the positive control group (p<0.05). The study demonstrates that the hydroalcoholic extract of Ziziphus jujuba significantly reduces inflammation markers such as TNF-α, NO, MPO, IL-1β, and IL-6 in a mouse model of ulcerative colitis. Additionally, itdownregulates the expression of pro-inflammatory genes, including iNOS and COX-2. These findings suggest that Z.jujuba extract has potential as an effective anti-inflammatory treatment for managing ulcerative colitis symptoms.

Probiotic Characteristics and the Anti-Inflammatory Effects of Lactiplantibacillus plantarum Z22 Isolated from Naturally Fermented Vegetables.

Currently, there is increasing interest in the commercial utilization of probiotics isolated from traditional fermented food products. Therefore, this study aimed to investigate the probiotic potential of Lactiplantibacillus plantarum (L. plantarum) Z22 isolated from naturally fermented mustard. The results suggest that L. plantarum Z22 exhibits good adhesion ability, antibacterial activity, safety, and tolerance to acidic conditions and bile salts. We further determined the anti-inflammatory mechanism and properties of L. plantarum Z22 and found that L. plantarum Z22 could significantly reduce the secretion of pro-inflammatory cytokines, including interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the expression of the pro-inflammatory mediator cyclooxygenase-2 (COX-2) protein in LPS-induced RAW 264.7 cells. In addition, L. plantarum Z22 also effectively inhibited the signaling pathways of nuclear factor κB (NF-κB) and mitogen-activated protein kinases (MAPKs). This effect can be attributed to a decrease in the levels of reactive oxygen species (ROS) and increased heme oxygenase-1 (HO-1) expression. Moreover, whole-genome sequencing revealed that L. plantarum Z22 contains gene-encoding proteins with anti-inflammatory functions, such as beta-glucosidase (BGL) and pyruvate kinase (PK), as well as antioxidant functions, including thioredoxin reductase (TrxR), tyrosine-protein phosphatase, and ATP-dependent intracellular proteases ClpP. In summary, these results indicated that L. plantarum Z22 can serve as a potential candidate probiotic for use in fermented foods such as yogurt (starter cultures), providing a promising strategy for the development of functional foods to prevent chronic diseases.

Investigation of the chemical composition and biological activities of Eremurus spectabilis M. Bieb through antioxidant, enzyme inhibition, COX-2 and iNOS assessment.

Eremurus spectabilis is widespread and used primarily for medicinal and culinary purposes. This study aimed to evaluate the chemical composition, antiradical and antioxidant activities, enzyme inhibitory activities, and anti-inflammatory properties of various extracts from the aerial parts of E. spectabilis. Various assays were used to investigate the antioxidant and enzyme inhibitory properties. The chemical composition of the tested extracts was analyzed using High-Performance Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry (HPLC-ESI-MS/MS). Additionally, the extracts were tested on isolated mouse colon tissue challenged with E. coli lipopolysaccharide (LPS) to replicate the inflammation and oxidative stress burden characteristic of inflammatory bowel diseases. In the chemical composition, vanillic, ferulic, 4-hydroxybenzoic acids were the prominent compounds. The greatest antioxidant activity was observed in the methanol and water extracts from the aerial parts. Enzyme inhibition tests showed that the ethyl acetate extract had the highest anti-acetylcholinesterase activity. The gene expression of pro-inflammatory cyclooxygenase-2 (COX-2) and pro-oxidant inducible nitric oxide synthase (iNOS) biomarkers were assayed. Among the extracts, the methanol extract was the most effective in blunting LPS-induced gene expression of COX-2. E. spectabilis may serve as a valuable source of phytochemicals for combating oxidative stress and inflammation-driven diseases, with a particular emphasis on colon inflammatory condition.

Cloning, characterization of β-glucosidase from Furfurilactobacillus rossiae in bioconversion and its efficacy.

Minor ginsenosides produced by β-glucosidase are interesting biologically and pharmacologically. In this study, new ginsenoside-hydrolyzing glycosidase from Furfurilactobacillus rossiae DCYL3 was cloned and expressed in Escherichia coli strain BL21. The enzyme converted Rb1 and Gyp XVII into Rd and compound K following the pathways: Rb1→Rd and Gyp XVII→F2→CK, respectively at optimal condition: 40°C, 15min, and pH 6.0. Furthermore, we examined the cytotoxicity, NO production, ROS generation, and gene expression of Gynostemma extract (GE) and bioconverted Gynostemma extract (BGE) in vitro against A549 cell lines for human lung cancer and macrophage RAW 264.7 cells for antiinflammation, respectively. As a result, BGE demonstrated significantly greater toxicity than GE against lung cancer at a dose of 500µg/mL but in normal cells showed lower toxicity. Then, we indicated an enhanced generation of ROS, which may be boosting cancer cell toxicity. By blocking the intrinsic way, BGE increased p53, Bax, Caspase 3, 9, and while Bcl2 is decreased. At 500µg/mL, the BGE sample was less toxic in normal cells and decreased the LPS-treated NO and ROS level to reduce inflammation. In addition, BGE inhibited the expression of pro-inflammatory genes COX-2, iNOS, IL-6, and IL-8 in RAW 264.7 cells than the sample of GE. In conclusion, FrBGL3 has considerable downstream applications for high-yield, low-cost, effective manufacture of minor ginsenosides. Moreover, the study's findings imply that BGE would be potential materials for anti-cancer and anti-inflammatory agent after consideration of future studies.

Protective Effects of Crotonis Semen Extract against Sepsis through NF-κB Pathway Inhibition.

Sepsis is an inflammatory condition causing organ failure due to an uncontrolled immune response to infection and remains a significant challenge. Crotonis Semen has displayed various pharmacological effects, yet its potential in protecting against sepsis and the mechanisms involved remains largely unclear. Here, we explored the antiseptic properties of Crotons Semen extract (CSE) in both LPS-stimulated J774 macrophages and mice subjected to sepsis through Cecal ligation and Puncture (CLP) or LPS induction. We found that CSE enhanced survival rates in mouse models with acute sepsis induced by CLP operation and LPS injection. Administering CSE also reduced levels of enzymes indicating organ damage, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK), in septic mice. Furthermore, CSE lowered the serum levels of inflammatory mediators and cytokines, such as NO, TNF-α, IL-1β, and IL-6, in septic mice. In LPS-stimulated J774 macrophages, CSE reduced the expression of pro-inflammatory proteins, including iNOS and COX-2. Moreover, CSE inhibited the phosphorylation of IκBα and IKK, key components of the NF-κB signaling pathway, thereby reducing inflammatory mediators and cytokines. These results demonstrate CSE's protective effects against sepsis through NF-κB pathway disruption, indicating its potential as a therapeutic option for acute inflammatory conditions.

Patuletin Ameliorates Inflammation and Letrozole-Induced Polycystic Ovarian Syndrome in Rats.

Concerns about inflammation-related issues affecting female reproductive health are growing. Chronic low-grade inflammation in women with polycystic ovarian syndrome (PCOS) affects follicular growth, ovulation, and androgen production. The present investigation aimed to elucidate the efficacy of flavonoid patuletin in ameliorating the letrozole-induced PCOS and associated inflammation in rats. Female Wistar rats (32 days old) were divided into five groups (n = 12): Group I, control; Group II, vehicle control; Group III, letrozole oral (1 mg/kg) for 28 days; Group IV and Group V treatment groups, patuletin i.p. (25 mg/kg) and clomiphene citrate + metformin i.p. (50 mg/kg + 300 mg/kg), respectively. Leterozole-induced PCOS and ovarian inflammation were ameliorated by patuletin, as reflected in the improved histopathology, prevention of cyst formation, significant upregulation of growth factors such as growth differentiation factor 9 (GDF-9) and bone morphogenetic protein-15 (BMP-15) expression, and a decrease in the pro-inflammatory cytokines TNF-α, IL-6, and COX-2. Additionally, the plasma levels of reproductive hormones were restored. Upregulation of FSH-R, PR, and CYP19a1, along with downregulation of ERα, LHR, CYP17a1, CYP11a1 and HSDβ17a1, showed the regulation of gonadotropin receptors and steroid biosynthesis genes in ovarian tissues. Patuletin demonstrated a promising protective approach against the biological model of PCOS by increasing the inflammation in ovarian tissues with consequent regulation of growth factors, enzymes, and hormones, and might be used as adjuvant therapy in the treatment of problems related to female reproductive health.

Anti-Melanogenic Potential of Malabar Spinach (Basella alba) in Human Melanoma Cells with Oxidative Stress Suppression and Anti-Inflammatory Activities.

Basella alba has been used in Thai remedies to treat skin disorders, but scientific evidence supporting its efficacy is currently limited. In this study, we investigated the inhibitory effects of B. alba extracts on melanin production using melanoma cells, as well as their impact on oxidative stress and inflammation in keratinocytes. The results demonstrate that B. alba extracts inhibited melanin content and cellular tyrosinase activity in 3-isobutyl-1-methylxanthine (IBMX)-induced melanoma cells by downregulating MITF and the pigmentary genes TYR, TRP-1, and DCT. Interestingly, the MITF regulator gene was inhibited by both the 50% and 95% ethanolic extracts of B. alba with levels of 0.97 ± 0.19 and 0.92 ± 0.09 of the control, respectively, which are comparable to those observed in the arbutin treatment group at 0.84 ± 0.05 of the control. Moreover, after hydrogen peroxide (H2O2) exposure, pretreatment with B. alba reduced lipid peroxidation byproducts and increased the levels of antioxidant-related genes, including SOD-1, GPX-1, and NRF2. Notably, the suppression of the POMC promoter gene in keratinocytes was observed, which may disrupt melanogenesis in melanocytes involving the MC1R signaling pathway. MC1R mRNA expression decreased in the treatments with 50% and 95% ethanolic extracts of B. alba, with relative levels of 0.97 ± 0.18 and 0.90 ± 0.10 of the control, respectively, similar to the arbutin-treated group (0.88 ± 0.25 of control). A significant reduction in nitric oxide was also observed in the B. alba-treated groups, along with a decrease in genes associated with pro-inflammatory cytokines, including IL-1β, IL-6, and COX-2. These findings suggest that B. alba has potential in the prevention of skin-related problems.

Increased Myocardial MAO-A, Atrogin-1, and IL-1β Expression in Transgenic Mice with Pancreatic Carcinoma-Benefit of MAO-A Inhibition for Cardiac Cachexia.

Cancer cachexia (CC) continues to challenge clinicians by massively impairing patients' prognosis, mobility, and quality of life through skeletal muscle wasting. CC also includes cardiac cachexia as characterized by atrophy, compromised metabolism, innervation and function of the myocardium through factors awaiting clarification for therapeutic targeting. Because monoamine oxidase-A (MAO-A) is a myocardial source of H2O2 and implicated in myofibrillar protein catabolism and heart failure, we presently studied myocardial MAO-A expression, inflammatory cells, and capillarization together with transcripts of pro-inflammatory, -angiogenic, -apoptotic, and -proteolytic signals (by qRT-PCR) in a 3x-transgenic (LSL-KrasG12D/+; LSL-TrP53R172H/+; Pdx1-Cre) mouse model of orthotopic pancreatic ductal adenoarcinoma (PDAC) compared to wild-type (WT) mice. Moreover, we evaluated the effect of MAO-A inhibition by application of harmine hydrochloride (HH, 8 weeks, i.p., no sham control) on PDAC-related myocardial alterations. Myocardial MAO-A protein content was significantly increased (1.69-fold) in PDAC compared to WT mice. PDAC was associated with an increased percentage of atrogin-1+ (p < 0.001), IL-1β+ (p < 0.01), COX2+ (p < 0.001), and CD68+ (p > 0.05) cells and enhanced transcripts of pro-inflammatory IL-1β (2.47-fold), COX2 (1.53-fold), TNF (1.87-fold), and SOCS3 (1.64-fold). Moreover, PDAC was associated with a reduction in capillary density (-17%, p < 0.05) and transcripts of KDR (0.46-fold) but not of VEGFA, Notch1, or Notch3. Importantly, HH treatment largely reversed the PDAC-related increases in atrogin-1+, IL-1β+, and TNF+ cell fraction as well as in COX2, IL-1β, TNF, and SOCS3 transcripts, whereas capillary density and KDR transcripts failed to improve. In mice with PDAC, increased myocardial pro-atrophic/-inflammatory signals are attributable to increased expression of MAO-A, because they are significantly improved with MAO-A inhibition as a potential novel therapeutic option. The PDAC-related loss in myocardial capillary density may be due to other mechanisms awaiting evaluation with consideration of cardiomyocyte size, cardiac function and physical activity.

Abstract P430: Angiotensin-(1-7) Induces A Decrease In Proinflammatory Genes Expression Through A Mas Receptor-Mediated Translocation To Brainstem Nuclei Of Spontaneously Hypertensive Rats

Mas receptor (MasR) displays differential trafficking in brainstem neurons from spontaneously hypertensive rats (SHRs): the fraction of dynamin-mediated internalized MasRs into early endosomes was larger and the fraction of MasRs recycled back to the plasma membrane was smaller in SHR than in Wistar neurons. Surprisingly, in SHR neurons but not in Wistar neurons, Ang-(1-7) induced MasR translocation to the nucleus. Our aim was to investigate the biological response elicited by MasR in the nucleus and whether MasR translocation was due to interaction with other receptors. We evaluated: 1) nitric oxide (NO) generation by DAF (diaminofluorescein) fluorescence; 2) interleukin (IL) 6, IL-1β, cyclooxygenase 2 (COX2) and NFkB expression by real time PCR; and 3) MasR interaction with AT1R and the dopamine type 2 receptor (D2R) by proximity ligation assay in brainstem neuronal primary cultures from Wistar and SHR rats incubated in the presence or absence of Ang-(1-7) or Ang-(1-7) + dynasore (DYN) (dynamin inhibitor) or Ang-(1-7) + A779 (MasR antagonist) during 30 min. Ang-(1-7) (100 nM) induced a decrease in the pro-inflammatory factors IL-6, IL-1β, COX2 and NFkB expression in brainstem neurons from Wistar and SHR rats which was blocked by A779, suggesting a MasR-mediated response. The effect of Ang-(1-7) was prevented when MasR internalization was prevented by DYN only in SHRs neurons but not in Wistar neurons, suggesting that the effect of Ang-(1-7) in SHR neurons is mediated by MasR translocation to the nucleus. Treatment of neurons with Ang-(1-7) induced an increase in NO in the nucleus of SHR but not of Wistar neurons and this effect was prevented by DYN and A779, suggesting that the Ang-(1-7)-induced NO production in the nucleus was due to MasR translocation to this compartment. MasR stimulation with Ang-(1-7) induced an increase in MasR-D2R heteromerization in SHR but not in Wistar neurons, and no change in MasR-AT1R heteromerization. Ou study showed that MasR translocation to the nucleus resulted in a reduction in pro-inflammatory genes expression and an increase in NO generation in SHR neurons. A fraction of MasR was translocated through the interaction with D2Rs, suggesting that this heteomer may be involved in the anti-inflammatory responses elicited by Mas translocation to the nucleus.

Indomethacin inhibits human seasonal coronaviruses at late stages of viral replication in lung cells: Impact on virus-induced COX-2 expression

Coronaviruses (CoV), zoonotic viruses periodically emerging worldwide, represent a constant potential threat to humans. To date, seven human coronaviruses (HCoV) have been identified: HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1, globally circulating in the human population (seasonal coronaviruses, sHCoV), and three highly-pathogenic coronaviruses, SARS-CoV, MERS-CoV and SARS-CoV-2. Although sHCoV generally cause only mild respiratory diseases, severe complications may occur in specific populations, highlighting the need for broad-spectrum anti-coronavirus drugs. Herein we show that indomethacin (INDO), a non-steroidal anti-inflammatory drug widely used in the clinic for its potent anti-inflammatory and analgesic properties, effectively inhibits the replication of Alpha-coronavirus HCoV-229E and Beta-coronavirus HCoV-OC43 in human lung-derived cells. Indomethacin does not interfere with HCoV binding or entry into target cells, but acts at late stages of the virus life cycle, inhibiting viral RNA synthesis and infectious viral particles production. Although INDO anti-inflammatory action is mediated by blocking cyclooxygenase-1 and -2 (COX-1/2) enzymatic activity, the antiviral effect appears to be cyclooxygenase-independent and is not mimicked by the potent COX-1/2 inhibitor aspirin. Interestingly we found that both seasonal HCoVs markedly (>100 fold) induce the expression of the pro-inflammatory mediator COX-2 in lung cells; notably, INDO-treatment was found to effectively inhibit virus-induced COX-2 expression at the transcriptional level, revealing an additional mechanism to prevent COX-2-mediated inflammatory reactions in HCoV-infected lung cells, besides COX activity inhibition. Altogether the results indicate that indomethacin, possessing both potent anti-inflammatory properties and a direct antiviral activity against HCoV, could be effective in the treatment of Alpha- and Beta-coronavirus infections.

The anti-inflammatory properties of green tea extract protect against gentamicin-induced kidney injury

We assessed in vivo the protective effects and underlying antioxidant and anti-inflammatory properties of dry green tee extract (GTE) on glomerular and tubular kidney function and structure in an experimental model of gentamicin (GEN)-induced nephrotoxicity. Wistar rats were divided into four groups and treated daily for 10 days. The control group received distilled water; the GTE group received 20 μg/g body weight (BW) GTE by gavage; the GEN group received 100 mg/g BW GEN intraperitoneally; and the GEN+GTE group received GTE and GEN simultaneously, as described above. At the beginning and end of treatment, the serum creatinine, fractional excretion of sodium and potassium, and plasma heme oxygenase (HO)-1 levels and oxidative stress (OS) were assessed. At the end of the experiment, kidney fragments were collected for histological evaluation and immunohistochemical studies of cyclooxygenase (COX)-2 and nuclear factor (NF)kB. The levels of interleukin (IL)-1b, IL-4, IL-6, IL-10 and monocyte chemotactic protein (MCP)-1 were measured in kidney tissue. The results showed that GTE attenuated significantly kidney structural injury and prevented GEN-induced kidney functional injury (glomerular and tubular function). GTE significantly attenuated the kidney tissue increase of the proinflammatory mediators NF-kB, COX2, IL-1b and MCP-1 and significantly increased the kidney expression of the anti-inflammatory cytokines IL-6 and IL-10. However, GTE did not prevent OS increase in GEN-treated animals. In conclusion, GTE protected against GEN nephrotoxicity, likely due to direct blockade of the inflammatory cascade, which might had occurred independently of its antioxidant effect.

Zingiber officinale Roscoe extract improves nigrostriatal dopaminergic activity in rotenone-induced Parkinsonian mice: Implication of COX-2/TNF-α/IL-6 and antioxidant enzyme crosstalk in the immunoinflammatory responses

Ethnopharmacological relevanceParkinson's disease (PD) is a chronic neurodegenerative disease that occurs progressively with time. Current PD treatments are symptomatic with moderate effects on striatal dopamine release. Previously, the ethnomedicinal benefits of Zingiber officinale Roscoe have been demonstrated to possess a broad range of pharmacological benefits, but no single data on its effect against nigrostriatal degeneration in PD model has been reported. AimProactive neuroprotective and pharmacotherapeutic approaches with asymptomatic effects are needed to prevent the progression of Parkinson's disease (PD) and maintain the appropriate population of dopaminergic neurons. Current treatments are symptomatic and can only elevate the striatal dopamine levels. Hence, the objective of the study is to elucidate the neuroprotective and neurorestorative properties of Zingiber officinale methanol extract (MEZO) on nigrostriatal degeneration implicated by immunoinflammatory responses in rotenone-challenged PD mice model. MethodsMale Swiss mice were injected with rotenone (2.5 mg/kg) intraperitoneally to induce PD symptoms 30 minutes prior to MEZO (50 and 100 mg/kg) and LD-CD (10 mg/kg) oral treatment for 28 days. Motor/neuromuscular behavior, dopamine, acetylcholinesterase (AChE), tyrosine hydroxylase (TH), α-synuclein (α-syn), cyclooxygenase-2 (COX-2), oxidative stress markers, inflammatory cytokines, and histopathology were evaluated. ResultsOur data showed that MEZO treatment attenuated sensorimotor and neuromuscular incompetence by up-regulating the expression of TH protein and dopamine release and maintaining AChE enzyme in the symptomatic mice. We observed that MEZO treatment prevented the formation of Lewis bodies (LBs) by inhibiting the aggregation of nigrostriatal α-Syn proteins, decreasing the release of pro-oxidant and pro-inflammatory mediators and cyclooxygenase-2 (COX-2) protein expression, increasing glutathione enzymes, and moderately abated the loss dopaminergic neurons in a dose-dependent effect in the symptomatic mice. ConclusionThese findings demonstrated that MEZO exhibited the potential neuroprotective and neurorestorative effect in the treatment and management of PD.

Therapeutic potential of sulfated glycosaminoglycan from seafood Asian green mussel (Perna viridis): Insights from an in vivo study

The Asian green mussel, Perna viridis, is widely consumed as seafood throughout the coastal regions of the Indo-Pacific area owing to its significant pharmaceutical and biomedical benefits. A pharmacologically active (1 → 3)/(1 → 4) linked sulfated glycosaminoglycan (PVP-2) with β-(1 → 3)-GlcNSp, and α-(1 → 4)-GlcAp units was isolated from P. viridis. PVP-2 (at 1–10 μg/mL) demonstrated a suppression of nitric oxide (NO) secretion in lipopolysaccharide-induced RAW 264.7 cells. Notably, PVP-2 at 5 μg/mL effectively restored NO levels (0.32 μg/mL) to homeostasis by downregulating excessive production (1.22 μg/mL). Furthermore, PVP-2 (at 22 mg/kg body weight) showed effective reduction of carrageenan-induced paw edema (82% inhibition at 5 h) in time dependent manner. This reduction was found to be comparable with standard treatment (87% inhibition of paw edema at 5 h). Treatment with PVP-2 (at 110 mg/kg body weight) resulted substantial inhibition of formalin-induced paw edema up to 10 days. At the end of the 10th day, the reduction in paw thickness was significantly greater (a four-fold increase) in the PVP-2 treated group compared to the formalin-induced group. Furthermore, PVP-2 displayed potent anti-inflammatory effect by attenuating cyclooxygenases (COX-1, 2) and 5-lipoxygenase (5-LOX) (IC50 < 2 mg/mL) enzymes with a higher selectivity index (IC50 COX-1/IC50 COX-2 ∼ 1.7) towards inducible pro-inflammatory COX-2. Therefore, inhibition of the NO production along with the reduction of paw edema, highlights the therapeutic potential of sulfated glycosaminoglycan from seafood Asian green mussel, as a naturally derived functional food to mitigate inflammation related disorders.

Imperata cylindrica polysaccharide ameliorates intestinal dysbiosis and damage in hyperuricemic nephropathy

In this study, a combination of adenine and potassium oxonate was utilized to establish a hyperuricemic nephropathy (HN) mouse model, aiming to elucidate the effect through which Imperata Cylindrica polysaccharide (ICPC-a) ameliorates HN. In HN mice, an elevation in the abundance of Erysipelatoclostridium, Enterococcus, Prevotella, and Escherichia-Shigella was observed, whereas Lactobacillus and Bifidobacterium declined. Additionally, the systemic reductions in the levels of acetate, propionate, and butyrate, along with a significant increase in indole content, were noted. HN mice demonstrated intestinal barrier impairment, as evidenced by diminished mRNA expression of ZO-1, Occludin, and Claudin-1 and increased Mmp-9 levels. The pro-inflammatory factors IL-6, IL-17, TNF-α, IFN-γ, and COX-2 were overexpressed. Subsequent gavage intervention with ICPC-a markedly mitigated the inflammatory response and ameliorated colon tissue damage. ICPC-a effectively regulated the abundance of gut microbiota and their metabolites, including short-chain fatty acids (SCFAs), bile acids (BAs), and indole, promoting the correction of metabolic and gut microbiota imbalances in HN mice. These findings underscored the capacity of ICPC-a as a prebiotic to modulate gut microbiota and microbial metabolites, thereby exerting a multi-pathway and multi-targeted therapeutic effect on HN.

The Exosomes of Stem Cells from Human Exfoliated Deciduous Teeth Suppress Inflammation in Osteoarthritis.

Hyaluronic acid injection is commonly used clinically to slow down the development of osteoarthritis (OA). A newly developed therapeutic method is to implant chondrocytes/stem cells to regenerate cartilage in the body. The curative effect of stem cell therapy has been proven to come from the paracrine of stem cells. In this study, exosomes secreted by stem cells from human exfoliated deciduous teeth (SHED) and hyaluronic acid were used individually to evaluate the therapeutic effect in slowing down OA. SHED was cultured in a serum-free medium for three days, and the supernatant was collected and then centrifuged with a speed difference to obtain exosomes containing CD9 and CD63 markers, with an average particle size of 154.1 nm. SW1353 cells were stimulated with IL-1β to produce the inflammatory characteristics of OA and then treated with 40 μg/mL exosomes and hyaluronic acid individually. The results showed that the exosomes successfully inhibited the pro-inflammatory factors, including TNF-α, IL-6, iNOS, NO, COX-2 and PGE2, induced by IL-1β and the degrading enzyme of the extrachondral matrix (MMP-13). Collagen II and ACAN, the main components of the extrachondral matrix, were also increased by 1.76-fold and 2.98-fold, respectively, after treatment, which were similar to that of the normal joints. The effect can be attributed to the partial mediation of SHED exosomes to the NF-κB pathway, and the ability of exosomes to inhibit OA is found not inferior to that of hyaluronic acid.