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Objectives:Inflammation, a crucial biological response defending the body against harmful stimuli, has been a central focus in medicinal research. Licorice root, rich in bioactive compounds, contains glabridin (GBD), a renowned natural flavonoid with anti-inflammatory and antioxidant properties. Despite its recognition, the precise molecular mechanisms underlying GBD's anti-inflammatory effects remain a subject of ongoing investigation. Methods:This study explores the impact of GBD on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages, aiming to unravel intricate molecular pathways, specifically focusing on the potential involvement of the adenosine monophosphate-activated protein kinase (AMPK)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. The study first determined the effective dose of GBD by measuring its impact on the production of pro-inflammatory mediators in response to LPS stimulation. The novelty of this study lies in subsequent examination of GBD's effects under LPS-induced inflammation, an aspect that has not been thoroughly explored in previous research. Results:GBD inhibits the production of LPS-induced pro-inflammatory cytokines and nitric oxide (NO). It also suppresses the expression of iNOS and IL-1β induced by LPS. Furthermore, GBD attenuates LPS-induced phosphorylation of JAK2 and STAT3, concurrently inhibiting AMPK phosphorylation. The study further elucidates the relationship between AMPK and JAK2/STAT3 using JAK2 inhibitor, AG490, and AMPK inhibitor, compound C (CC). Importantly, CC not only inhibits the expression of AMPK but also suppresses the expression of JAK2 and STAT3. This observation strongly suggests that GBD modulates the AMPK/JAK2/STAT3 signaling pathways in LPS-stimulated macrophages. Conclusion:This study reveals that GBD is a promising anti-inflammatory agent with novel inhibitory effects on the AMPK/JAK2/STAT3 pathway, highlighting its potential therapeutic value for inflammatory diseases.

Yen-Ting Lin, David F. Pyke, and Jayashankar M. Swaminathan describe the application of blockchain to supply chain traceability, highlighting common barriers to implementing blockchain and approaches that companies have used to overcome these barriers.

Background:Macrophage migration plays a critical role in inflammation and the development of pathological processes. Thus, inhibiting macrophage migration is a potential approach for reducing inflammation. Besides, mitigation of inflammatory mediators also inhibits macrophage migration. Morin hydrate (MH), a bioflavonoid found in fruits, vegetables, and herbs, has demonstrated various pharmacological effects, including anti-inflammatory and immunosuppressive properties. However, the specific molecular mechanisms underlying MH's anti-inflammatory effects and its impact on macrophage migration remain unclear. This study focused on MH's anti-inflammatory molecular mechanism and also elucidated how it is associated with inhibiting macrophage migration. Methods:The anti-inflammatory and antimigration effects of MH were investigated in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, a murine macrophage cell line. The production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) were assessed by various assays. Additionally, the expression of key signaling molecules, such as extracellular signal-regulated kinase (ERK), JNK, p65, pSrc, focal adhesion kinase (FAK), β-catenin, COX-2, p-p38, and p-Akt, was analyzed in response to MH treatment. Results:MH treatment reduced LPS-induced NO production and downregulated the mRNA and protein expression of iNOS in RAW264.7 cells. It concentration dependently inhibited the expression of ERK and JNK. At a high concentration of 20 µM, MH also suppressed the expression of p65, pSrc, and pFAK. Moreover, MH effectively attenuated LPS-induced β-catenin expression, while it did not exhibit a significant effect on COX-2, p-p38, and p-Akt expressions in LPS-stimulated RAW264.7 cells. Furthermore, MH pretreatment inhibited the migration of LPS-induced macrophages. Conclusion:This study reveals that MH exerts its anti-inflammatory effects by inhibiting NO production, downregulating iNOS expression, and modulating ERK/JNK and p65 phosphorylation. Additionally, MH suppresses Src/FAK phosphorylation and downregulates β-catenin expression induced by LPS. The findings demonstrate a complex interplay between the inflammatory response and MH's impact on macrophage migration being intertwined with its anti-inflammatory properties.

ABSTRACTIntroduction: As it is importance to understand the involvement of platelets in the initiation and propagation of thrombosis, antiplatelet drugs have come to the forefront of atherothrombotic disease treatment. Dual antiplatelet therapy of aspirin plus clopidogrel has its benefits, but it also has its limitations with regard to its pharmacologic properties and adverse effects. For these reasons, within the last decade or so, the investigation of novel antiplatelet agents has prospered.Areas covered: In this review, we discuss the unique pharmacodynamic properties of several antiplatelet drugs with their possible potential molecular of mechanisms on inhibiting platelet aggregation.Expert opinion: Considering multiple synergetic pathways of platelet activation and their close interplay with coagulation, the current treatment strategies are not only based on platelet inhibition, they also rely on the attenuation of procoagulant activity, inhibition of thrombin generation, and enhancement of clot dissolution. Current guidelines recommend various antiplatelet agents in addition to aspirin for patients with acute coronary syndromes. The advantages of these agents, as repute mortality, may be associated with off-target effects of the drug. Hence, further studies are required to facilitate the physician’s choice of the most appropriate antiplatelet agents for each patient for thrombosis treatment.

Objectives Oxidative stress induces chronic inflammatory diseases in aerobic organisms, and antioxidants from plants represent an efficient strategy to prevent this condition. Morin hydrate (MH), a bioactive flavonoid, has a wide range of pharmacological properties, including anti-inflammatory and anti-oxidant. This study evaluated the protective effects of MH on lipoteichoic acid (LTA)-induced inflammation in RAW 264.7 macrophages by testing the main oxidative and inflammatory biomarkers and also investigating the molecular pathways involved.Methods The antioxidant and anti-inflammatory effects of MH were evaluated in a cell-free system and RAW264.7 cells. Quantitative real-time PCR (RT-qPCR) and assay kits were used to measure the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) mRNA, as well as the activity of antioxidant enzymes. The effects of MH on LTA-induced inducible nitric oxide synthase (iNOS), IL-1β, and TNF-α mRNA and protein expression were also evaluated by RT-qPCR and Western blotting.Results MH reduced DPPH and ABTS radicals in a cell-free system and LTA-induced ROS and NO production in RAW264.7 cells. MH upregulated Nrf2 and HO-1 mRNA expression and reversed LTA-mediated reduction of antioxidant enzymes, at a high concentration of 20 µM pretreated cells. MH also effectively attenuated LTA-induced iNOS, IL-1β, and TNF-α mRNA and protein expression, and these effects were reversed by ML385.Conclusions The study found that the Nrf2/HO-1 played role in the inhibition of LTA-induced oxidative stress in macrophages by MH. This study may consider to be a promising induced macrophage-targeted strategy via regulating anti-oxidative defense to control inflammatory-related disease.