kurarinone and Inflammation

Ulcerative colitis (UC) is relevant to dysregulation of inflammation and immune processes. Sophora flavescens Aiton is a classic medicine widely used in the treatment of UC in ancient and modern China, alkaloids and flavonoids are the main components. Previous studies reveal that Sophora flavescens Aiton total flavonoids extracts (SFE) exert an anti-UC effect by regulating the intestinal microbe structure and restoring the balance of the "host-microbe" co-metabolic network in UC mice. However, whether SFE influences immune inflammation remains unclear, which is the core link to UC disease. It also remains to be verified flavonoids are the material basis that plays a role in SFE.. To identify the action mechanism of the immune-inflammatory regulation of SFE and its main active component Kurarinone against UC.. This study constructed UC mice and abnormal immune RAW 264.7 cell models, and subsequently used western blotting and flow cytometry (FCM) to evaluate the effects of SFE on the NF-κB pathway and the regulation of immunity in UC mice. Kurarinone was screened from flavonoid compounds of SFE by lipopolysaccharide (LPS)-induced RAW 264.7 cells, and its effect was subsequently investigated in UC mice. Western blotting, ELISA, FCM, and RT-PCR were used to determine the regulation of Kurarinone on the Th17/Treg differentiation and the JAK2/STAT3 signaling pathway.. SFE regulated the differentiation of Th17/Treg in peripheral blood and inhibited immune-inflammatory response to treat UC. Various flavonoid components in SFE inhibited the synthesis of IL-6 and TNF-α in RAW 264.7 cells, among which Kurarinone had better effect. This study revealed the therapeutic effects of Kurarinone in UC mice for the first time. Kurarinone promoted the secretion of SIgA to improve the regulation of the intestinal mucosal barrier and resistance to pathogens. It also regulated the transcription level of RORγt and Foxp3 in colon, decreased the expression of pro-inflammatory factor IL-17A and up-regulated the expression of immunosuppressive factors TGF-β1 and IL-10 in colon. Furthermore, Kurarinone restored intestinal immune system homeostasis by down-regulating the JAK2/STAT3 signaling pathway and regulating the balance of Th17/Treg cell differentiation in UC.. SFE, especially the flavonoid ingredients represented by Kurarinone, has significant effects on immunoregulation against UC. And their mechanism of effect is related to inhibiting the activation of JAK2/STAT3 signaling pathway and regulating differentiation of Th17/Treg cells.. Immunoregulatory; Kurarinone; Th17 cells; Treg cells; Ulcerative colitis.

Topics: Animals; Colitis; Colitis, Ulcerative; Disease Models, Animal; Flavonoids; Homeostasis; Inflammation; Mice; Sophora; T-Lymphocytes, Regulatory; Th17 Cells

Cerebral hemorrhage is a fatal disease that causes severe damage to local nerve function. The purpose of this research is to analyze the effect of kurarinone on hemin-induced neuroinflammation and neurotoxicity. In our study, according to the results of bioinformatics analysis, we hypothesized that kurarinone might modulate cerebral hemorrhage advancement via the insulin-like growth factor 1/phosphoinositide 3-kinase/protein kinase B (IGF1/PI3K/Akt) signaling. Kurarinone promoted M2 microglia polarization, and curbed M1 polarization and inflammation in human microglial cells (HMC3) cells with hemin treatment. Besides, kurarinone upregulated IGF1 expression and activated the PI3K/Akt signaling pathway in hemin-treated HMC3 cells. In addition, downregulation of IGF1 or inhibition of the PI3K/Akt signaling weakened the effects of kurarinone on microglia polarization and inflammation in HMC3 cells with hemin treatment. Kurarinone alleviated apoptosis and oxidative damage of SH-SY5Y cells co-cultured with hemin-treated HMC3 cells. In conclusion, kurarinone lessened hemin-induced neuroinflammation and microglia-mediated neurotoxicity by regulating microglial polarization through modulating the IGF1/PI3K/Akt signaling. These results delivered a new prospective therapeutic drug for the treatment of cerebral hemorrhage.

Topics: Cerebral Hemorrhage; Hemin; Humans; Inflammation; Insulin-Like Growth Factor I; Microglia; Neuroblastoma; Neuroinflammatory Diseases; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction