euscaphic-acid and Inflammation

Atopic dermatitis (AD) is a complex and multifactorial skin disease characterized by skin inflammation and intense pruritus. There are many commercially available treatments such as topical corticosteroids and immunosuppressants to treat of AD, but their effectiveness is limited, and frequent use of these treatments can cause serious side effects. Therefore, the development of new therapeutic agents is necessary for the treatment of AD. Hence, an alternative agent that was derived from natural products that are effective and safe for AD treatment was investigated using experimental models. The biological activity of euscaphic acid has anti-inflammatory, anticoagulant, and antioxidant effects. Despite the various biomedical properties of euscaphic acid, its therapeutic effects on AD have not been well studied. In this study, we investigated the effects of euscaphic acid on skin inflammation and pruritus in AD mouse model. The effects of euscaphic acid were investigated in activated human epidermal keratinocytes and leukemia T lymphoblast cell lines, and Dermatophagoides farina extract and 2,4-dinitrochlorobenzene-induced AD mouse model. Euscaphic acid ameliorated AD properties, such as the expression of inflammatory cytokines and activation of transcription factors. In addition, euscaphic acid reduced critical factors for pruritus such as immunoglobulin E hyperproduction, mast cell invasion, and interleukin-33 expression. Taken together, euscaphic acid could be a potent therapeutic agent for the treatment of AD.

Topics: Animals; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; Inflammation; Mice; Mice, Inbred BALB C; Pruritus; Skin; Triterpenes

The pro-inflammatory cytokine interleukin-1beta (IL-1β) plays critical roles in pathogenesis of osteoarthritis (OA). Tormentic acid (TA), a triterpene isolated from Rosa rugosa, has anti-inflammatory activity. However, the anti-inflammatory effect of TA on OA is still unclear. So, in the present study, we examined the effect of TA on IL-1β-induced inflammatory response in primary human OA chondrocytes. Our results demonstrated that TA significantly decreased the IL-1β-stimulated expression of matrix metalloproteinase-3 (MMP-3) and MMP-13. It also inhibited the IL-1β-induced expression of inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the production of NO and prostaglandin E2 (PGE2) in human OA chondrocytes. Furthermore, TA greatly inhibited the IL-1β-induced NF-κB activation. In conclusion, this study is the first to demonstrate the anti-inflammatory activity of TA in human OA chondrocytes. TA significantly inhibits the IL-1β-induced inflammatory response by suppressing the NF-κB signaling pathway. Thus, TA may be a potential agent in the treatment of OA.

Topics: Anti-Inflammatory Agents; Cells, Cultured; Chondrocytes; Humans; Inflammation; Interleukin-18; NF-kappa B; Osteoarthritis; Signal Transduction; Triterpenes

Tormentic acid (TA) is a triterpene isolated from the stem bark of the plant Vochysia divergens and has been reported to exhibit anticancer, anti‑inflammatory and anti‑atherogenic properties. However, the functions of TA in hydrogen peroxide (H2O2)‑induced oxidative stress and inflammation in rat vascular smooth muscle cells (RVSMCs) remain unclear. Therefore, the present study aimed to investigate whether TA suppressed H2O2‑induced oxidative stress and inflammation in RVSMCs, and to determine its molecular mechanisms. The present study demonstrated that TA inhibited reactive oxygen species (ROS) generation, induced H2O2 in RVSMCs, and inhibited H2O2-induced expression of inducible nitric oxide synthase (iNOS) and NADPH oxidase (NOX) in RVSMCs. In addition, TA significantly decreased the production of tumor necrosis factor‑α (TNF‑α), interleukin 6 (IL‑6) and IL‑1β. Furthermore, TA pretreatment prevented nuclear factor‑κB (NF‑κB) subunit p65 phosphorylation and NF‑κB inhibitor α (IκBα) degradation induced by H2O2 in RVSMCs. TA is, therefore, suggested to inhibit H2O2-induced oxidative stress and inflammation in RVSMCs via inhibition of the NF‑κB signaling pathway. TA may have potential as a pharmacological agent in the prevention or treatment of atherosclerosis.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Atherosclerosis; Cell Survival; Cells, Cultured; Female; Hydrogen Peroxide; Inflammation; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; NF-kappa B; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Signal Transduction; Triterpenes

As an attempt to search for bioactive natural products exerting anti-inflammatory activity, we have evaluated the anti-inflammatory effects of euscaphic acid (19α-hydroxyursane-type triterpenoids, EA) isolated from roots of Rosa rugosa and its underlying molecular mechanisms in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. EA concentration-dependently reduced the production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) induced by LPS in RAW 264.7 macgophages. Consistent with these data, expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein and iNOS, COX-2, TNF-α, and IL-1β mRNA were inhibited by EA in a concentration-dependent manner. In addition, EA attenuated LPS-induced DNA binding and transcriptional activity of nuclear factor-kappa B (NF-κB), which was accompanied by a parallel reduction of degradation and phosphorylation of inhibitory kappa Bα (IκBα) and consequently by decreased nuclear translocation of p65 subunit of NF-κB. Pretreatment with EA significantly inhibited the LPS-induced phosphorylation of IκB kinase β (IKKβ), p38, and JNK, whereas the phosphorylation of ERK1/2 was unaffected. Furthermore, EA interfered with the LPS-induced clustering of TNF receptor-associated factor 6 (TRAF6) with interleukin receptor associated kinase 1 (IRAK1) and transforming growth factor-β-activated kinase 1 (TAK1). Taken together, these results suggest that EA inhibits LPS-induced inflammatory responses by interference with the clustering of TRAF6 with IRAK1 and TAK1, resulting in blocking the activation of IKK and MAPKs signal transduction to downregulate NF-κB activations.

Topics: Animals; Cell Line; Cyclooxygenase 2; Dinoprostone; Extracellular Signal-Regulated MAP Kinases; I-kappa B Proteins; Inflammation; Interleukin-1 Receptor-Associated Kinases; Interleukin-1beta; JNK Mitogen-Activated Protein Kinases; Lipopolysaccharides; Macrophages; MAP Kinase Kinase Kinases; MAP Kinase Signaling System; Mice; NF-kappa B; NF-KappaB Inhibitor alpha; Nitric Oxide; Nitric Oxide Synthase Type II; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Phytotherapy; RNA, Messenger; Rosa; TNF Receptor-Associated Factor 6; Toll-Like Receptor 4; Transcription Factor RelA; Transcription, Genetic; Triterpenes; Tumor Necrosis Factor-alpha

Experiments were designed to address whether the pentacyclic triterpene tormentic acid isolated from the stem bark of the plant Vochysia divergens exerts oral anti-allodynic properties in two models of chronic pain in mice: neuropathic pain caused by partial ligation of the sciatic nerve and inflammatory pain produced by intraplantar injection of Complete Freund's Adjuvant. Oral administration of tormentic acid (30 mg/kg) twice a day for several consecutive days produced time-dependent and pronounced anti-allodynia effect in both ispsilateral and contralateral paws after plantar injection of Complete Freund's Adjuvant. The inhibition observed was 82+/-9% and 100+/-11%, respectively. Interestingly, tormentic acid did not inhibit paw oedema formation following Complete Freund's Adjuvant plantar injection. Tormentic acid (30 mg/kg, p.o.) and gabapentin (70 mg/kg, p.o.), given twice a day, inhibited markedly the neuropathic allodynia induced by partial ligation of the sciatic nerve, with inhibition of 91+/-19% and 71+/-16%, respectively. The anti-allodynic action of tormentic acid was not associated with impairment of the motor activity of the animals. Together, the present results indicate that tormentic acid or its derivatives might be of potential interest in the development of new clinically relevant drugs for the management of persistent neuropathic and inflammatory allodynia.

Topics: Acetates; Amines; Analgesics; Animals; Chronic Disease; Cyclohexanecarboxylic Acids; Female; Freund's Adjuvant; Gabapentin; gamma-Aminobutyric Acid; Inflammation; Ligation; Male; Mice; Motor Activity; Pain; Peripheral Nervous System Diseases; Phytotherapy; Plant Bark; Plant Extracts; Sciatic Nerve; Time Factors; Touch; Triterpenes