-
Frontiers in Nutrition 2023Seafood is highly enriched in n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs), particularly eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA,... (Review)
Review
Seafood is highly enriched in n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs), particularly eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3), in contrast to the ultra-processed foods included in the modern Western diet that have high levels of n-6 linoleic acid (LA, 18:2 n-6), precursor for the pro-inflammatory n-6 arachidonic acid (ARA, 20:4 n-6). The capacity of marine lipids to reduce plasmatic triglycerides and blood pressure have been well-described. Moreover, recent studies have also raised evidence of a potential regulatory action of marine lipids on inflammation, the immune system, and food allergy (FA). FA is considered one of the main concerns to become life threatening in food safety. The prevalence of this emerging global problem has been increasing during the last two decades, especially in industrialized countries. About a 6-8% of young children and 2-4% of adults is estimated to be affected by FA. The main objective of the current study is to update the existing knowledge, but also the limitations, on the potential impact of marine lipids and their lipid mediators in regulating immunity, inflammation, and ultimately, food allergies. In particular, the focus is on the effect of marine lipids in modulating the key factors that control the sensitization and effector phases of FA, including gut microbiota (GM), inflammation, and immune system response. Results in animal models highlight the positive effect that consuming marine lipids, whether as a supplement or through seafood consumption, may have a relevant role in improving gut dysbiosis and inflammation, and preventing or reducing the severity of FA. However, more systematic studies in humans are needed to optimize such beneficial actions to each particular FA, age, and medical condition to reach an effective clinical application of marine lipids to improve FAs and their outcomes.
PubMed: 38035353
DOI: 10.3389/fnut.2023.1254681 -
Antibiotics (Basel, Switzerland) Jun 2024Dental caries is a global health problem that requires better prevention measures. One of the goals is to reduce the prevalence of the cariogenic Gram-positive bacterium...
Dental caries is a global health problem that requires better prevention measures. One of the goals is to reduce the prevalence of the cariogenic Gram-positive bacterium . We have recently shown that naturally occurring arachidonic acid (AA) has both anti-bacterial and anti-biofilm activities against this bacterium. An important question is how these activities are affected by other anti-bacterial compounds commonly used in mouthwashes. Here, we studied the combined treatment of AA with chlorhexidine (CHX), cetylpyridinium chloride (CPC), triclosan, and fluoride. Checkerboard microtiter assays were performed to determine the effects on bacterial growth and viability. Biofilms were quantified using the MTT metabolic assay, crystal violet (CV) staining, and live/dead staining with SYTO 9/propidium iodide (PI) visualized by spinning disk confocal microscopy (SDCM). The bacterial morphology and the topography of the biofilms were visualized by high-resolution scanning electron microscopy (HR-SEM). The effect of selected drug combinations on cell viability and membrane potential was investigated by flow cytometry using SYTO 9/PI staining and the potentiometric dye DiOC2(3), respectively. We found that CHX and CPC had an antagonistic effect on AA at certain concentrations, while an additive effect was observed with triclosan and fluoride. This prompted us to investigate the triple treatment of AA, triclosan, and fluoride, which was more effective than either compound alone or the double treatment. We observed an increase in the percentage of PI-positive bacteria, indicating increased bacterial cell death. Only AA caused significant membrane hyperpolarization, which was not significantly enhanced by either triclosan or fluoride. In conclusion, our data suggest that AA can be used together with triclosan and fluoride to improve the efficacy of oral health care.
PubMed: 38927206
DOI: 10.3390/antibiotics13060540 -
Otolaryngologic Clinics of North America Apr 2024Aspirin-exacerbated respiratory disease (AERD) is a subtype of chronic rhinosinusitis with polyps (CRSwNP) and asthma with higher recurrence of nasal polyps after... (Review)
Review
Aspirin-exacerbated respiratory disease (AERD) is a subtype of chronic rhinosinusitis with polyps (CRSwNP) and asthma with higher recurrence of nasal polyps after surgery and severe asthma. Patients with CRSwNP and asthma should be screened for AERD by detailed history of aspirin/nonsteroidal anti-inflammatory drug reactions and review of medications that may mask aspirin reaction or directly by aspirin challenge. Treatment of AERD may require more intensive therapy, including endoscopic sinus surgery, daily aspirin therapy, leukotriene modifiers, or biologics.
Topics: Humans; Rhinitis; Asthma, Aspirin-Induced; Aspirin; Anti-Inflammatory Agents, Non-Steroidal; Nasal Polyps; Sinusitis; Asthma; Chronic Disease
PubMed: 37833102
DOI: 10.1016/j.otc.2023.09.006 -
Scientific Reports Dec 2023Jasminum elongatum (JE), an ethnic Chinese medicine, is widely used in the Lingnan region of China, because of its analgesic and antidiarrheal action, as well as its...
Jasminum elongatum (JE), an ethnic Chinese medicine, is widely used in the Lingnan region of China, because of its analgesic and antidiarrheal action, as well as its anti-inflammatory effects in gastrointestinal diseases. However, whether JE could against ulcerative colitis (UC) remains unclear. This research aims to reveal JE in treating UC and clarify the underlying mechanism. We used the 2.5% dextran sulfate sodium (DSS)-induced UC mice (C57BL/6J) to evaluate the therapeutic effects of JE. Metabolomics of serum and network pharmacology were combined to draw target-metabolite pathways. Apart from that, the targets of associated pathways were confirmed, and the mechanism of action was made clear, using immunohistochemistry. The pharmacodynamic results, including disease activity index (DAI), histological evaluation, and inflammatory cytokines in colon tissues, demonstrated that JE significantly relieved the physiological and pathological symptoms of UC. Network pharmacology analysis indicated 25 core targets, such as TNF, IL-6, PTGS2 and RELA, and four key pathways, including the NF-κB signaling pathway and arachidonic acid metabolism pathway, which were the key connections between JE and UC. Metabolomics analysis identified 45 endogenous differential metabolites and 9 metabolic pathways by enrichment, with the arachidonic acid metabolism pathway being the main metabolism pathway, consistent with the prediction of network pharmacology. IκB, p65 and COX-2 were identified as key targets and this study demonstrated for the first time that JE reverses 2.5% DSS-induced UC in mice via the IκB/p65/COX-2/arachidonic acid pathway. This study reveals the complex mechanisms underlying the therapeutic effects of JE on UC and provides a new approach to identifying the underlying mechanisms of the pharmacological action of Chinese natural medicines such as JE.
Topics: Animals; Mice; Mice, Inbred C57BL; Colitis, Ulcerative; Jasminum; Arachidonic Acid; Cyclooxygenase 2; Network Pharmacology; Colon; NF-kappa B; Dextran Sulfate; Disease Models, Animal; Colitis
PubMed: 38105335
DOI: 10.1038/s41598-023-49792-w -
Reproductive Toxicology (Elmsford, N.Y.) Sep 2023Arachidonic acid (AA), an ω-6 polyunsaturated fatty acid involved in signalling pathways that drive cell fate decisions, has an enhancing role in the immunomodulatory...
Arachidonic acid (AA), an ω-6 polyunsaturated fatty acid involved in signalling pathways that drive cell fate decisions, has an enhancing role in the immunomodulatory effect on mesenchymal stem cells and the vasculogenesis of embryonic stem cells. 3D embryoid bodies (EBs) from pluripotent stem cells (PSCs) have been used as in vitro models for embryotoxicity for various compounds/drugs. Valproic acid (VA), a common anti-epileptic drug, is known to be embryotoxic and cause malformations in embryos. As early embryogenesis depends on AA, we investigated the embryo protective effects of AA against the embryotoxic drug VA in this study. The effects of AA on the proliferation and cell cycle parameters of PSCs were studied. In particular, the potential of AA to abrogate VA-induced embryotoxicity in vitro was evaluated using ROS detection and antioxidant assays. In response to AA, we observed modulation in cell proliferation of induced pluripotent stem cells (iPSCs) and pluripotent NTERA-2 embryonal carcinoma (EC) cells. The present study substantiates the cytoprotective effects of AA against VA. These results imply that AA plays a critical role in the proliferation and differentiation of iPSCs and EC cells and protects the EBs from cytotoxic damage, thereby ensuring normal embryogenesis. Thus, the bioactive lipid AA may be explored for supplementation to benefit pregnant women treated with long-term anti-epileptic drugs to prevent in-utero fetal growth malformations.
Topics: Humans; Female; Pregnancy; Embryoid Bodies; Arachidonic Acid; Pluripotent Stem Cells; Embryonic Stem Cells; Cell Differentiation
PubMed: 37454977
DOI: 10.1016/j.reprotox.2023.108438 -
Metabolism, fibrosis, and apoptosis: The effect of lipids and their derivatives on keloid formation.International Wound Journal Feb 2024Keloids, pathological scars resulting from skin trauma, have traditionally posed significant clinical management challenges due to their persistence and high recurrence... (Review)
Review
Keloids, pathological scars resulting from skin trauma, have traditionally posed significant clinical management challenges due to their persistence and high recurrence rates. Our research elucidates the pivotal roles of lipids and their derivatives in keloid development, driven by underlying mechanisms of abnormal cell proliferation, apoptosis, and extracellular matrix deposition. Key findings suggest that abnormalities in arachidonic acid (AA) synthesis and non-essential fatty acid synthesis are integral to keloid formation. Further, a complex interplay exists between lipid derivatives, notably butyric acid (BA), prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), and the regulation of hyperfibrosis. Additionally, combinations of docosahexaenoic acid (DHA) with BA and 15-deoxy-Δ12,14-Prostaglandin J2 have exhibited pronounced cytotoxic effects. Among sphingolipids, ceramide (Cer) displayed limited pro-apoptotic effects in keloid fibroblasts (KFBs), whereas sphingosine 1-phosphate (S1P) was found to promote keloid hyperfibrosis, with its analogue, FTY720, demonstrating contrasting benefits. Both Vitamin D and hexadecylphosphorylcholine (HePC) showed potential antifibrotic and antiproliferative properties, suggesting their utility in keloid management. While keloids remain a prevalent concern in clinical practice, this study underscores the promising potential of targeting specific lipid molecules for the advancement of keloid therapeutic strategies.
Topics: Humans; Keloid; Extracellular Matrix; Fibrosis; Apoptosis; Lipids; Fibroblasts
PubMed: 38339798
DOI: 10.1111/iwj.14733 -
Frontiers in Pharmacology 2023Inflammation is a defensive response of the body and the pathological basis of many diseases. However, excessive inflammation and chronic inflammation impair the...
Inflammation is a defensive response of the body and the pathological basis of many diseases. However, excessive inflammation and chronic inflammation impair the homeostasis of the organism. Arachidonic acid (AA) has a close relationship with inflammation and is the main mediator of the pro-inflammatory response. Based on the prodrug principle, the new pharmaceutical compound aspirin eugenol ester (AEE) was designed and synthesized. However, the effects of AEE on key enzymes, metabolites and inflammatory signaling pathways in the AA metabolic network have not been reported. In this study, the anti-inflammation effects of AEE were first investigated in mice and RAW264.7 cells in LPS induced inflammation model. Then, the changes of the key enzymes and AA metabolites were explored by RT-PCR and targeted metabolomics. Moreover, the regulatory effects on NF-kB and MAPKS signaling pathways were explored by Western Blotting. Results indicated that AEE significantly reduced the number of leukocyte and increased the lymphocyte percentage. AEE decreased the expression levels of IL-1β, IL-6, IL-8 and TNF-α both and . In the liver of mice, AEE downregulated the levels of AA, prostaglandin D (PGD) and upregulated 12- hydroxyeicosatetraenoic acid (12-HETE). However, the changes of PGE, PGF, 6-keto-prostaglandin F (6-KETO-PGF), 9-hydroxy-octadecenoic acid (9- HODE), 13-HODE, 15-HETE, docosahexaenoic acid (DHA) and thromboxane B (TXB) were not significant. Additionally, it was found that AEE decreased the relative mRNA expression levels of p65 and p38 and the ratio of p-p65/p65. It was concluded that AEE might inhibit the LPS-induced inflammatory response through the regulation of AA metabolism. This study provides the theoretical foundation for the development of AEE as a medicinal anti-inflammatory drug.
PubMed: 37705535
DOI: 10.3389/fphar.2023.1220780 -
Inflammopharmacology Aug 2023Burn management is a natural and distinctly programmed process involving overlapping phases of hemostasis, inflammation, proliferation and remodeling. Burn wound healing... (Review)
Review
Burn management is a natural and distinctly programmed process involving overlapping phases of hemostasis, inflammation, proliferation and remodeling. Burn wound healing involves initiation of inflammation, re-epithelialization, granulation, neovascularization and wound contraction. Despite the availability of multiple preparations for management of burn wound, there is dire need for efficacious alternative agents. Current approaches for burn wound management include pharmaceutical agents and antibiotics. However, high cost of synthetic drugs and accelerated resistance to antibiotics is challenging for both developed and developing nations. Among alternative options, medicinal plants have been a biocompatible, safe and affordable source of preventive/curative approaches. Due to cultural acceptance and patient compliance, there has been a focus on the use of botanical drugs and phytochemicals for burn wound healing. Keeping in consideration of medicinal herbs and phytochemicals as suitable therapeutic/adjuvant agents for burn wound management, this review highlights therapeutic potential of 35 medicinal herbs and 10 phytochemicals. Among these, Elaeis guineensis, Ephedra ciliate and Terminalia avicennioides showed better burn wound healing potential with varied mechanisms such as modulation of TNF-alpha, inflammatory cytokines, nitric oxide, eicosanoids, ROS and leukocyte response. Phytochemicals (oleanolic acid, ursolic acid, kirenol) also showed promising role in burn wound management though various pathways involving such as down regulation of TNF-alpha, IL-6 and inflammatory mediators including plasma proteases and arachidonic acid metabolites. This review provides a pavement for therapeutic/adjuvant use of potential botanical drugs and novel druggable phyto-compounds to target skin burn injury with diverse mechanisms, affordability and safety profile.
Topics: Humans; Plants, Medicinal; Tumor Necrosis Factor-alpha; Wound Healing; Inflammation; Phytochemicals
PubMed: 37204694
DOI: 10.1007/s10787-023-01246-5 -
Lipids in Health and Disease Oct 2023Mead acid (MA, 5,8,11-eicosatrienoic acid) is an n-9 polyunsaturated fatty acid (PUFA) and a marker of essential fatty acid deficiency, but nonetheless generally draws... (Review)
Review
Mead acid (MA, 5,8,11-eicosatrienoic acid) is an n-9 polyunsaturated fatty acid (PUFA) and a marker of essential fatty acid deficiency, but nonetheless generally draws little attention. MA is distributed in various normal tissues and can be converted to several specific lipid mediators by lipoxygenase and cyclooxygenase. Recent pathological and epidemiological studies on MA raise the possibility of its effects on inflammation, cancer, dermatitis and cystic fibrosis, suggesting it is an endogenous multifunctional PUFA. This review summarizes the biosynthesis, presence, metabolism and physiological roles of MA and its relation to various diseases, as well as the significance of MA in PUFA metabolism.
Topics: Humans; Fatty Acids, Unsaturated; 8,11,14-Eicosatrienoic Acid; Inflammation
PubMed: 37838679
DOI: 10.1186/s12944-023-01937-6 -
JCI Insight Dec 2023Gout commonly manifests as a painful, self-limiting inflammatory arthritis. Nevertheless, the understanding of the inflammatory and immune responses underlying gout...
Gout commonly manifests as a painful, self-limiting inflammatory arthritis. Nevertheless, the understanding of the inflammatory and immune responses underlying gout flares and remission remains ambiguous. Here, based on single-cell RNA-Seq and an independent validation cohort, we identified the potential mechanism of gout flare, which likely involves the upregulation of HLA-DQA1+ nonclassical monocytes and is related to antigen processing and presentation. Furthermore, Tregs also play an essential role in the suppressive capacity during gout remission. Cell communication analysis suggested the existence of altered crosstalk between monocytes and other T cell types, such as Tregs. Moreover, we observed the systemic upregulation of inflammatory and cytokine genes, primarily in classical monocytes, during gout flares. All monocyte subtypes showed increased arachidonic acid metabolic activity along with upregulation of prostaglandin-endoperoxide synthase 2 (PTGS2). We also detected a decrease in blood arachidonic acid and an increase in leukotriene B4 levels during gout flares. In summary, our study illustrates the distinctive immune cell responses and systemic inflammation patterns that characterize the transition from gout flares to remission, and it suggests that blood monocyte subtypes and Tregs are potential intervention targets for preventing recurrent gout attacks and progression.
Topics: Humans; Gout; Monocytes; Arachidonic Acid; Symptom Flare Up; Gene Expression Profiling
PubMed: 38063198
DOI: 10.1172/jci.insight.171417