ABSTRACT
Hyperuricemia (HUA) is a metabolic disease characterized by the increase of serum uric acid (UA) level. Sargentodoxae Caulis (SC) is a commonly used herbal medicine for the treatment of gouty arthritis, traumatic swelling, and rheumatic arthritis in clinic. In this study, a total of fifteen compounds were identified in SC water extract using UHPLC-Q-TOF-MS/MS, including three phenolic acids, seven phenolic glycosides, four organic acids, and one lignan. Then, to study the hypouricemia effect of SC, a HUA mouse model was induced using a combination of PO, HX, and 20% yeast feed. After 14 days of treatment with the SC water extract, the levels of serum UA, creatinine (CRE), blood urea nitrogen (BUN) were reduced significantly, and the organ indexes were restored, the xanthine oxidase (XOD) activity were inhibited as well. Meanwhile, SC water extract could ameliorate the pathological status of kidneys and intestine of HUA mice. Additionally, quantitative real-time PCR (qRT-PCR) and western blotting results showed that SC water extract could increase the expression of ATP binding cassette subfamily G member 2 (ABCG2), organic cation transporter 1 (OCT1), organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3), whereas decrease the expression of glucose transporter 9 (GLUT9). This study provided a data support for the clinical application of SC in the treatment of HUA.
Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 2 , Hyperuricemia , Uric Acid , Xanthine Oxidase , Animals , Mice , Hyperuricemia/drug therapy , Male , ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism , Uric Acid/blood , Xanthine Oxidase/metabolism , Disease Models, Animal , Glucose Transport Proteins, Facilitative/metabolism , Kidney/drug effects , Blood Urea Nitrogen , Creatinine/blood , Plant Extracts/pharmacology , Plant Extracts/chemistry , Organic Anion Transporters/metabolism , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Organic Anion Transport Protein 1/metabolism , Hydroxybenzoates/isolation & purification , Hydroxybenzoates/pharmacologyABSTRACT
This study investigated the function of κ-carrageenan polysaccharide in immune regulation. The immune response of RAW 264.7 cells treated with κ-carrageenan polysaccharide was explored by MTT assay, general morphological observation, neutral red phagocytosis assay, Griess method, fluorescence method, and enzyme-linked immunosorbent assay. In addition, TLR4 blocking experiment and double-fluorescence immunostaining were performed on cells to demonstrate their immune response mechanism. Results show that κ-carrageenan polysaccharide not only promotes cell proliferation but also activates RAW 264.7 cells, thereby improving the cells' phagocytic capability, NO production, and tumor necrosis factor-α (TNF-α) secretion. In addition, the use of TLR4-specific inhibitors can significantly mediate the increased TNF-α secretion induced by κ-carrageenan polysaccharide. The RAW 264.7 cells treated with κ-carrageenan polysaccharide show upregulated TLR4 expression, and the main subunit of NF-κB (p65) is translocated. These results support the immunomodulatory function of κ-carrageenan polysaccharide in RAW 264.7 cells.
