Scoparone

Exp Cell Res. 2015 Feb 15;331(2):267-77.

Scoparone attenuates RANKL-induced osteoclastic differentiation through controlling reactive oxygen species production and scavenging.[Pubmed: 25576385]

Scoparone, one of the bioactive components of Artemisia capillaris Thunb, has various biological properties including immunosuppressive, hepatoprotective, anti-allergic, anti-inflammatory, and antioxidant effects.
METHODS AND RESULTS:
This study aims at evaluating the anti-osteoporotic effect of Scoparone and its underlying mechanism in vitro. Scoparone demonstrated potent cellular antioxidant capacity. It was also found that Scoparone inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and suppressed cathepsin K and tartrate-resistant acid phosphatase (TRAP) expression via c-jun N-terminal kinase (JNK)/extracellular signal-regulated kinase (ERK)/p38-mediated c-Fos-nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) signaling pathway. During osteoclast differentiation, the production of general reactive oxygen species (ROS) and superoxide anions was dose-dependently attenuated by Scoparone. In addition, Scoparone diminished NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 1 (Nox1) expression and activation via the tumor necrosis factor receptor-associated factor 6 (TRAF6)-cSrc-phosphatidylinositol 3-kinase (PI3k) signaling pathway and prevented the disruption of mitochondrial electron transport chain system. Furthermore, Scoparone augmented the expression of superoxide dismutase 1 (SOD1) and catalase (CAT).
CONCLUSIONS:
The overall results indicate that the inhibitory effect of Scoparone on RANKL-induced osteoclast differentiation is attributed to the suppressive effect on ROS and superoxide anion production by inhibiting Nox1 expression and activation and protecting the mitochondrial electron transport chain system and the scavenging effect of ROS resulting from elevated SOD1 and CAT expression.in system and the scavenging effect of ROS resulting from elevated SOD1 and CAT expression.

Food Chem. 2013 Nov 15;141(2):723-30.

Scoparone inhibits adipocyte differentiation through down-regulation of peroxisome proliferators-activated receptor γ in 3T3-L1 preadipocytes.[Pubmed: 23790840]

This study was performed to investigate the effect of Scoparone on the differentiation of 3T3-L1 preadipocytes.
METHODS AND RESULTS:
Scoparone inhibited triglyceride (TG) accumulation in the mature adipocytes, evidenced by Oil-red O staining and intracellular quantification. Real time-PCR analysis showed that Scoparone significantly down-regulated the mRNA expression of key adipogenic transcription factors, PPARγ, C/EBPα, compared with mature adipocytes. Scoparone appeared to reduce mRNA expression of SREBP1c and FAS being related to the late stage of adipogenesis. Furthermore, aP2 and CD36/FAT, as adipocyte-specific genes, were decreased in mature adipocytes by Scoparone treatment. Moreover, Scoparone inhibited the up-regulated expression of PPARγ target genes by rosiglitazone to near that observed in cells treated with GW9662. The luciferase assay revealed that Scoparone negatively regulates the transcriptional activity of PPARγ. Chromatin immunoprecipitation assay also showed that participation of Scoparone in the regulation of PPARγ.
CONCLUSIONS:
Collectively, Scoparone has a PPARγ antagonic effect and suppresses differentiation through down-regulation of adipogenic genes by PPARγ inhibition in 3T3-L1 preadipocytes.

Phytopathology, 1989, 78(12):1678-82.

Accumulation of scoparone, a phytoalexin associated with resistance of citrus to Phytophthora citrophthora.[Reference: WebLink]

METHODS AND RESULTS:
Citrus species resistant and susceptible to Phytophthora citrophthora were compared for production of Scoparone in the bark 1-8 days after inoculation with the pathogen. Concentrations of Scoparone were higher (maximum 440 ug/g fr wt after 4 days) and increased more rapidly in the resistant species within 24 hr after inoculation. In the susceptible species the maximum concentration was 41.6 micrograms/g fr wt. The lesion length caused by P. citrophthora in citrus bark 4 days after inoculation was 2.5-5.0 mm in the resistant, compared with more than 11 mm in the susceptible.
CONCLUSIONS:
Scoparone inhibited mycelial growth of P. citrophthora and spore germination of six other phytopathogenic fungi in vitro. Radioactivity was incorporated into Scoparone in infected citrus bark that had been treated with 14C-phenylalanine. Resistant citrus species, treated with the inhibitor aminooxyacetic acid (AOA) before inoculation, became susceptible to P. citrophthora.

Cell Physiol Biochem . 2016;40(1-2):277-286.

Scoparone Protects Against Pancreatic Fibrosis via TGF-β/Smad Signaling in Rats[Pubmed: 27855406]

Abstract Background/aims: This study was to investigate the influence of Scoparone on pancreatic fibrosis in vitro and in vivo. Methods: Pancreatic stellate cells (PSCs) were isolated from pancreas tissue blocks, and cultured for 3-5 generations for the experiment. PSCs were treated with Scoparone in different doses as experimental groups, salvianolic acid B as a positive control and PBS as a blank group. We measured the effects of Scoparone on cellular proliferation, oxidative stress, epithelial-mesenchymal transition (EMT), and pancreatic fibrosis. Cellular oxidative stress was detected by using commercially available kits. The impact of Scoparone on EMT and fibrosis was detected through immunofluorescence or western blotting. Results: Compared with the control group, Scoparone significantly inhibited stellate cell proliferation, and reduced MDA, the expression of mesenchymal makers, and increased the levels of SOD and the expression of E-cadherin (P < 0.05). Western blot analysis showed that Scoparone downregulated the expression of TGF-β and p-smad2/3, and upregultated the expression of smad7 (P < 0.05). Conclusion: Scoparone can reduce the levels of oxidative stress, repress pancreatic stellate cells activation, and alleviate fibrosis by regulating TGF-β/Smad pathway.

Chem Pharm Bull (Tokyo). 1989 May;37(5):1297-9.

The effect of scoparone, a coumarin derivative isolated from the Chinese crude drug Artemisiae capillaris flos, on the heart.[Pubmed: 2630096]

METHODS AND RESULTS:
In the present study, Scoparone isolated from Artemisia Capillaris Flos has been investigated to determine its pharmacological properties on the heart. Scoparone was found to cause the increase in coronary flow and heart rate, but did not affect cardiac output, left ventricular pressure or left ventricular work in the isolated perfused heart. Scoparone at 25 mg/kg and 50 mg/kg, p.o. had a marked inhibitory effect on the ST wave depression.
CONCLUSIONS:
Consequently it is suggested that Scoparone has antianginal action.

Exp Mol Med. 2015 Mar 6;47:e145.

Scoparone interferes with STAT3-induced proliferation of vascular smooth muscle cells.[Pubmed: 25744297]

Scoparone, which is a major constituent of Artemisia capillaries, has been identified as an anticoagulant, hypolipidemic, vasorelaxant, anti-oxidant and anti-inflammatory drug, and it is used for the traditional treatment of neonatal jaundice.
METHODS AND RESULTS:
Therefore, we hypothesized that Scoparone could suppress the proliferation of VSMCs by interfering with STAT3 signaling. We found that the proliferation of these cells was significantly attenuated by Scoparone in a dose-dependent manner. Scoparone markedly reduced the serum-stimulated accumulation of cells in the S phase and concomitantly increased the proportion of cells in the G0/G1 phase, which was consistent with the reduced expression of cyclin D1, phosphorylated Rb and survivin in the VSMCs. Cell adhesion markers, such as MCP-1 and ICAM-1, were significantly reduced by Scoparone. Interestingly, this compound attenuated the increase in cyclin D promoter activity by inhibiting the activities of both the WT and active forms of STAT3. Similarly, the expression of a cell proliferation marker induced by PDGF was decreased by Scoparone with no change in the phosphorylation of JAK2 or Src. On the basis of the immunofluorescence staining results, STAT3 proteins phosphorylated by PDGF were predominantly localized to the nucleus and were markedly reduced in the Scoparone-treated cells. In summary, Scoparone blocks the accumulation of STAT3 transported from the cytosol to the nucleus, leading to the suppression of VSMC proliferation through G1 phase arrest and the inhibition of Rb phosphorylation. This activity occurs independent of the form of STAT3 and upstream of kinases, such as Jak and Src, which are correlated with abnormal vascular remodeling due to the presence of an excess of growth factors following vascular injury.
CONCLUSIONS:
These data provide convincing evidence that Scoparone may be a new preventative agent for the treatment of cardiovascular diseases.

Int Immunopharmacol. 2014 Nov;23(1):127-33.

Protective effects of scoparone against lipopolysaccharide-induced acute lung injury.[Pubmed: 25151099]

METHODS AND RESULTS:
The purpose of this study was to investigate the protective effects and molecular mechanisms of Scoparone on lipopolysaccharide (LPS)-induced acute lung injury in mice. Mice model of acute lung injury (ALI), induced by intranasal instillation of LPS, was used to investigate the protective effects of Scoparone in vivo. The alveolar macrophages were used to investigate the molecular mechanisms of Scoparone in vitro. The results showed that Scoparone treatment remarkably attenuated LPS-induced pulmonary edema, histological severities, myeloperoxidase activity, and TNF-α, IL-6 and IL-1β production in vivo. We also found that Scoparone inhibited LPS-induced TLR4 expression, NF-κB activation, TNF-α, IL-6 and IL-1β production in alveolar macrophages in vitro.
CONCLUSIONS:
In conclusion, our results suggest that Scoparone has a protective effect on LPS-induced ALI via suppression of TLR4-mediated NF-κB signaling pathways.