sauchinone and Disease-Models--Animal

Whole-transcriptome analysis and western blotting of sauchinone-treated HepG2 cells demonstrated that sauchinone regulated genes relevant to cholesterol metabolism and synthesis. In particular, it was found that the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) was downregulated, and the expression of low density lipoprotein receptor (LDLR) was upregulated in sauchinone-treated HepG2 cells. Consequently, LDL-cholesterol (LDL-C) uptake was increased. As a transcriptional regulator of PCSK9 expression, sterol regulatory elements binding protein-2 (SREBP-2) was proposed by transcriptome analysis and western blotting. Oral administration of sauchinone increased hepatic LDLR through PCSK9 inhibition in obese mice and showed the reduced serum LDL-C levels and downstream targets of SREBP-2. Thus, it is evident that sauchinone reduces hepatic steatosis by downregulating the expression of hepatic PCSK9 via SREBP-2.

Topics: Animals; Benzopyrans; Cholesterol; Cholesterol, LDL; Dioxoles; Disease Models, Animal; Fatty Liver; Gene Expression Regulation; Gene Regulatory Networks; Hep G2 Cells; Homeostasis; Humans; Lipid Metabolism; Liver; Mice; Proprotein Convertase 9; Receptors, LDL; Sterol Regulatory Element Binding Protein 2; Transcriptome

Osteoarthritis (OA) is a common degenerative joint disease for which currently no anti-inflammatory therapy is available. Sauchinone (SAU), a key bioactive compound derived from Saururus chinensis, which has shown remarkable anti-inflammatory effects.. To evaluate the effect of SAU on OA progression, mouse chondrocytes were pretreated with SAU and subsequently stimulated with interleukin (IL)-1β. We found that SAU reduced the production of pro-inflammatory cytokines, such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), and IL-6. SAU also inhibited the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) at both the gene and protein level. Moreover, SAU promoted the expression of aggrecan, while inhibiting the expression of catabolic factors, such as matrix metalloproteinases (MMPs) and thrombospondin motifs 5 (ADAMTS-5) in mouse chondrocytes. Col X, vascular endothelial growth factor-A (VEGF)-A, and Runx2, major markers of hypertrophic chondrocytes, were markedly elevated following IL-1β stimulation, and were reduced by SAU treatment while having the opposite effect on Col II. Mechanistically, we found that SAU inhibited nuclear factor kappa B (NF-κB) and activated the Nrf2/HO-1 pathway. The beneficial effects of SAU were also observed in vivo using a mouse OA model.. Our findings indicate that SAU may be a potential novel therapeutic for the treatment of OA.

Topics: Animals; Anti-Inflammatory Agents; Benzopyrans; Cell Survival; Cells, Cultured; Chondrocytes; Dioxoles; Disease Models, Animal; Extracellular Matrix; Female; Heme Oxygenase-1; Interleukin-1beta; Male; Membrane Proteins; Mice, Inbred C57BL; NF-E2-Related Factor 2; NF-kappa B; Osteoarthritis; Signal Transduction