forsythiaside and Inflammation

Chronic pain is frequently reported in clinical practice. Therefore, it is important to identify effective therapy to relieve pain. In this work, we selected Forsythoside B (FB), a phenylethanoid glycoside isolated from Forsythia suspensa (Thunb.) Vahl, to evaluate its effect in modulating inflammatory pain induced by complete Freund's adjuvant (CFA) and the involved mechanisms. We discovered that FB could attenuate inflammatory pain triggered by CFA injection and exert anti-anxiety effects. In detail, proinflammatory cytokines, consisting of IL-6 and TNF-α, were decreased after FB administration in the CFA-injected mice. Furthermore, the FB application ameliorated the activation of ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP), the microglia and astrocytes markers respectively. Therefore, our findings indicate that FB could be a promising treatment for chronic inflammatory pain.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Chronic Pain; Freund's Adjuvant; Glucosides; Hyperalgesia; Inflammation; Mice

Dairy cow mastitis is the most common disease encountered in dairy farming. Lipopolysaccharides (LPS), among the major virulence-related factors produced by Escherichia coli, stimulate mammary gland inflammation and cause its damage, thereby affecting milk yield and quality. Forsythoside A (FTA) is among the main active components of forsythia. Recent pharmacological studies have demonstrated that FTA possesses anti-inflammatory, antiviral, antioxidant, and other biological activities. This study investigated the effects of the FTA-activated AMP-activated protein kinase (AMPK) signaling pathway on LPS-induced autophagy, apoptosis, and inflammatory damage in bovine mammary epithelial (MAC-T) cells. Cell activity was measured using the Cell Counting Kit 8. Moreover, real-time quantitative polymerase chain reaction and western blot analyses were used to detect expression levels of autophagic, apoptotic, and inflammatory factors, as well as those of oxidative stress-related genes and proteins. The annexin-FITC/PI assay and immunofluorescence assay were used to detect the apoptosis rate and LC3B expression, respectively. We found that FTA attenuated LPS-induced inhibition of MAC-T cell proliferation, reduced mRNA expression of related inflammatory factors, relieved oxidative stress, and exerted protective effects on MAC-T cells. Additionally, FTA activated autophagy, attenuated inhibition of autophagy flow, and inhibited apoptosis. Autophagy and apoptosis were mainly regulated through the AMPK/mTOR/ULK1 pathway. The aforementioned FTA-induced effects were inhibited by the administration of Compound C (CC; an AMPK inhibitor). Taken together, these results indicate that FTA can alleviate LPS-induced inflammation and oxidative stress in MAC-T cells, attenuate impairments in autophagy, and inhibit apoptosis. However, these effects were blocked by CC, which suggests that FTA inhibits LPS-induced autophagy, apoptosis, and inflammatory damage in MAC-T cells by activating the AMPK pathway.

Topics: AMP-Activated Protein Kinases; Animals; Apoptosis; Autophagy; Cattle; Female; Inflammation; Lipopolysaccharides; Signal Transduction; TOR Serine-Threonine Kinases

Inflammation is a general pathological phenomenon during severe disturbances to the homeostasis. Forsythiaside A (FA) and forsythiaside B (FB), isolated from the dried fruit of Forsythia suspensa (Thunb.) Vahl, are phenylethanoid compounds that show a significant anti-inflammatory effect. However, the properties and therapeutic mechanisms of this effect have not yet been systematically elucidated.. In this study, the anti-inflammatory effects of FA and FB were investigated in CuSO. FA and FB inhibited neutrophils migration to the damaged neuromasts and remarkably reduced CuSO. Our results indicate that FA and FB possess remarkable anti-inflammatory properties, protecting against CuSO

Topics: Animals; Anti-Inflammatory Agents; Copper Sulfate; Glycosides; Inflammation; Metabolomics; Neutrophil Infiltration; Proteomics; Zebrafish

Acute lung injury (ALI) is a life-threatening disease without effective pharmacotherapies, so far. Forsythia suspensa is frequently used in the treatment of lung infection in traditional Chinese medicine. In search for natural anti-inflammatory components, the activity and the underlying mechanism of Forsythoside A (FA) from Forsythia suspensa were explored. In the present paper, BALB/c mice and murine RAW 264.7 cells were stimulated by LPS to establish inflammation models. Data showed that FA inhibited the production of TNF-α and IL-6 and the activation of STAT3 in LPS-stimulated RAW 264.7 cells. Additionally, FA increased the expression level of microRNA-124 (miR-124). Furthermore, the inhibitory effect of FA on STAT3 was counteracted by the treatment of miR-124 inhibitor. Critically, FA ameliorated LPS-induced ALI pathological damage, the increase in lung water content and inflammatory cytokine, cells infiltration and activation of the STAT3 signaling pathway in BALB/c mice. Meanwhile, FA up-regulated the expression of miR-124 in lungs, while administration with miR-124 inhibitor attenuated the protective effects of FA. Our results indicated that FA alleviates LPS-induced inflammation through up-regulating miR-124 in vitro and in vivo. These findings indicate the potential of FA and miR-124 in the treatment of ALI.

Topics: Acute Lung Injury; Animals; Glycosides; Inflammation; Interleukin-6; Lipopolysaccharides; Macrophages; Male; Mice; Mice, Inbred BALB C; MicroRNAs; Models, Biological; Protective Agents; RAW 264.7 Cells; Signal Transduction; STAT3 Transcription Factor; Tumor Necrosis Factor-alpha; Up-Regulation

Forsythoside A (FTA), the major bioactive component extracted from Forsythiae fructus, has multiple biological properties especially anti-inflammatory property. Staphylococcus aureus (S. aureus), a Gram-positive organism, is one of most common pathogens that cause bovine mastitis. This study evaluated the anti-inflammatory effect of FTA in S. aureus-stimulated primary bovine mammary epithelial cells (bMEC). Primary bovine mammary epithelial cells were isolated from the mammary tissue of lactating cows and identified as bMEC. The cell viability of bMEC was analyzed by MTT. The bMEC were stimulated with S. aureus in the presence or absence of FTA. Subsequently, the expression level of pro-inflammatory cytokines was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Nuclear factor-κB (NF-κB), inhibitor protein of NF-κB (IκBα), p38, extracellular signal-regulated protein kinase (ERK), and c-JunN-terminal kinase (JNK) were measured by western blotting. The results showed that the cell viability was not affected by the FTA. FTA markedly down-regulated the expressions of TNF-α, IL-1β and IL-6 in S. aureus-stimulated bMEC. In addition, FTA was found to suppress S. aureus-induced NF-κB and MAPKs activation in a dose-dependent manner. These results indicated that FTA exerted anti-inflammatory property in S. aureus-stimulated bMEC by interfering the activation of NF-κB and MAPKs signaling pathways. Thereby, FTA may be a potential therapeutic agent against inflammatory disease.

Topics: Animals; Anti-Inflammatory Agents; Cattle; Cell Survival; Cells, Cultured; Cytokines; Epithelial Cells; Gene Expression Profiling; Glycosides; Inflammation; Models, Biological; Real-Time Polymerase Chain Reaction; Staphylococcus aureus

Inflammation and biofilm formation by Staphylococcus aureus (S. aureus) are common causes of periprosthetic infection and loosening. Recently, we identified that forsythiaside is bacteriostatic for S. aureus and methicillin-resistant S. aureus (MRSA). The purpose of the present study was to examine the effect of forsythiaside on S. aureus and MRSA adhesion and biofilm formation on the surface of titanium alloy, which is a popular material for orthopedic joint prostheses.. Two strains of S. aureus and MRSA were used for in vitro experiments. The spread plate method, confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM) were used to characterize antimicrobial activity of forsythiaside. Real-time polymerase chain reaction (RT-PCR) and western blotting were used to investigate the inhibitory level of forsythiaside required for titanium-associated inflammation.. Direct colony counting showed that 16 μg/mL forsythiaside significantly inhibited S. aureus and MRSA adhesion on titanium alloy discs in 2 h. CLSM and SEM showed that higher concentrations (> 30 mg/mL) of forsythiaside effectively inhibited the adhesion of S. aureus and MRSA on the surface of the titanium disc in 24 h. Forsythiaside was capable of attenuating Ti-induced activation of nuclear factor-κB signaling, targeting IκB kinase-α (IKKα) kinases of macrophages, and influencing the expression of NF-κB downstream cytokines.. These observations suggest that forsythiaside is a potential agent for the treatment of Ti implant-associated infection and inflammation.

Topics: Alloys; Bacterial Adhesion; Biofilms; Glycosides; Humans; Inflammation; Macrophages; Methicillin-Resistant Staphylococcus aureus; NF-kappa B; Staphylococcus aureus; Titanium