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Norisoboldine

$197

  • Brand : BIOFRON

  • Catalogue Number : BD-P0831

  • Specification : 97%

  • CAS number : 23599-69-1

  • Formula : C18H19NO4

  • Molecular Weight : 313.35

  • PUBCHEM ID : 14539911

  • Volume : 25mg

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Catalogue Number

BD-P0831

Analysis Method

Specification

97%

Storage

-20℃

Molecular Weight

313.35

Appearance

Powder

Botanical Source

This product is isolated and purified from the roots of Lindera aggregata

Structure Type

Category

SMILES

COC1=C(C2=C3C(CC4=CC(=C(C=C42)OC)O)NCCC3=C1)O

Synonyms

Laurelliptin/norisobolidine/4H-Dibenzo[de,g]quinoline-1,9-diol, 5,6,6a,7-tetrahydro-2,10-dimethoxy-, (6aS)-/(6aS)-2,10-Dimethoxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-1,9-diol

IUPAC Name

Applications

Norisoboldine alleviates joint destruction in rats with adjuvant-induced arthritis by reducing RANKL, IL-6, PGE(2), and MMP-13 expression.[Pubmed: 23396374 ]Norisoboldine ameliorates collagen-induced arthritis through regulating the balance between Th17 and regulatory T cells in gut-associated lymphoid tissues.[Pubmed: 25481498]Toxicol Appl Pharmacol. 2015 Jan 1;282(1):90-9. Norisoboldine (NOR), the main active ingredient of the dry root of Lindera aggregata, was previously proven to have substantial therapeutic effects on collagen-induced arthritis (CIA) in mice by oral administration. However, it exhibited a very poor bioavailability in normal rats. The pharmacokinetic-pharmacodynamics disconnection attracts us to explore its anti-arthritic mechanism in more detail. METHODS AND RESULTS: In this study, NOR, administered orally, markedly attenuated the pathological changes in CIA rats, which was accompanied by the down-regulation of pro-inflammatory cytokines and the up-regulation of anti-inflammatory cytokine IL-10. Pharmacokinetic studies demonstrated that the plasma concentration of NOR was moderately elevated in CIA rats compared with normal rats, but it was still far lower than the minimal effective concentration required for inhibiting the proliferation and activation of T lymphocytes in vitro. Interestingly, NOR was shown to regulate the balance between Th17 and regulatory T (Treg) cells in the intestinal lymph nodes more strikingly than in other tissues. It could increase the expression of Foxp3 mRNA in both gut and joints, and markedly up-regulate the number of integrin α4β7 (a marker of gut source)-positive Foxp3(+) cells in the joints of CIA rats. These results suggest that the gut might be the primary action site of NOR, and NOR exerts anti-arthritis effect through regulating the balance between Th17 and Treg cells in intestinal lymph nodes and yielding a trafficking of lymphocytes (especially Treg cells) from the gut to joint. CONCLUSIONS: The findings of the present study also provide a plausible explanation for the anti-arthritic effects of poorly absorbed compounds like NOR.Acta Pharmacol Sin. 2013 Mar;34(3):403-13. To explore the effects of Norisoboldine (NOR), a major isoquinoline alkaloid in Radix Linderae, on joint destruction in rats with adjuvant-induced arthritis (AIA) and its underlying mechanisms. METHODS AND RESULTS: AIA was induced in adult male SD rats by intradermal injection of Mycobacterium butyricum in Freund's complete adjuvant at the base of the right hind paw and tail. From d 14 after immunization, the rats were orally given NOR (7.5, 15, or 30 mg/kg) or dexamethasone (0.5 mg/kg) daily for 10 consecutive days. Joint destruction was evaluated with radiological scanning and H&E staining. Fibroblast-like synoviocytes (FLS) were prepared from fresh synovial tissues in the AIA rats. The expression of related proteins and mRNAs were detected by ELISA, Western blotting and RT-PCR. In AIA rats, NOR (15 and 30 mg/kg) significantly decreased the swelling of paws and arthritis index scores, and elevated the mean body weight. NOR (30 mg/kg) prevented both the infiltration of inflammatory cells and destruction of bone and cartilage in joints. However, NOR (15 mg/kg) only suppressed the destruction of bone and cartilage, but did not obviously ameliorate synovial inflammation. NOR (15 and 30 mg/kg) significantly decreased the serum levels of receptor activator of nuclear factor κB ligand (RANKL), IL-6, PGE2, and MMP-13, but not the osteoprotegerin and MMP-1 levels. The mRNA levels of RANKL, IL-6, COX-2, and MMP-13 in synovium were also suppressed. Dexamethasone produced similar effects in AIA rats as NOR did, but without elevating the mean body weight. In the cultured FLS, treatment with NOR (10 and 30 mmol/L) significantly decreased the secretion of RANKL, IL-6, PGE2, and MMP-13 proteins. Furthermore, the treatment selectively prevented the activation of MAPKs, AKT and transcription factor AP-1 component c-Jun, but not the recruitment of TRAF6 or the activation of JAK2/STAT3. Treatment of the cultured FLS with the specific inhibitors of p38, ERK, AKT, and AP-1 significantly decreased the secretion of RANKL, IL-6, PGE2, and MMP-13 proteins. CONCLUSIONS: NOR can alleviate joint destruction in AIA rats by reducing RANKL, IL-6, PGE2, and MMP-13 expression via the p38/ERK/AKT/AP-1 pathway.

Density

1.3±0.1 g/cm3

Solubility

Acetontrile; Water; Methanol; DMSO

Flash Point

288.3±30.1 °C

Boiling Point

553.0±50.0 °C at 760 mmHg

Melting Point

InChl

InChl Key

HORZNQYQXBFWNZ-LBPRGKRZSA-N

WGK Germany

RID/ADR

HS Code Reference

Personal Projective Equipment

Correct Usage

For Reference Standard and R&D, Not for Human Use Directly.

Meta Tag

provides coniferyl ferulate(CAS#:23599-69-1) MSDS, density, melting point, boiling point, structure, formula, molecular weight etc. Articles of coniferyl ferulate are included as well.>> amp version: coniferyl ferulate

No Technical Documents Available For This Product.

PMID

29449535

Abstract

Norisoboldine (NOR), a natural aryl hydrocarbon receptor (AhR) agonist, has been demonstrated to attenuate ulcerative colitis (UC) and induce the generation of Treg cells. Under UC condition, hypoxia widely exists in colonic mucosa, and secondary changes of microRNAs (miRs) expressions and glycolysis contribute to Treg differentiation. At present, we worked for exploring the deep mechanisms for NOR-promoted Treg differentiation in hypoxia and its subsequent anti-UC action from the angle of AhR/miR or AhR/glycolysis axis. Results showed that NOR promoted Treg differentiation in hypoxia and the effect was stronger relative to normoxia. It activated AhR in CD4+ T cells under hypoxic microenvironment; CH223191 (a specific AhR antagonist) and siAhR-3 abolished NOR-promoted Treg differentiation. Furthermore, the progress of glycolysis, levels of Glut1 and HK2, and expression of miR-31 rather than miR-219 and miR-490 in CD4+ T cells were downregulated by NOR treatment under hypoxic microenvironment. However, HK2 plasmid but not miR-31 mimic significantly interfered NOR-enhanced Treg polarization. In addition, NOR reduced NAD+ and SIRT1 levels, facilitated the ubiquitin-proteasomal degradation of SUV39H1 protein, and inhibited the enrichment of H3K9me3 at -1, 201 to -1,500 region of Foxp3 promoter in CD4+ T cells under hypoxic microenvironment, which was weakened by HK2 plasmid, CH223191, and siAhR-3. Finally, the correlation between NOR-mediated activation of AhR, repression of glycolysis, regulation of NAD+/SIRT1/SUV39H1/H3K9me3 signals, induction of Treg cells, and remission of colitis was confirmed in mice with DSS-induced colitis by using CH223191 and HK2 plasmid. In conclusion, NOR promoted Treg differentiation and then alleviated the development of colitis by regulating AhR/glycolysis axis and subsequent NAD+/SIRT1/SUV39H1/H3K9me3 signaling pathway.

Title

Norisoboldine, a Natural AhR Agonist, Promotes Treg Differentiation and Attenuates Colitis via Targeting Glycolysis and Subsequent NAD +/SIRT1/SUV39H1/H3K9me3 Signaling Pathway

Author

Qi Lv 1 , Kai Wang 1 , Simiao Qiao 1 , Ling Yang 1 , Yirong Xin 1 , Yue Dai 2 , Zhifeng Wei 3

Publish date

2018 Feb 15

PMID

27315014

Abstract

Context: The nuclear factor of activated T-cells (NFAT) is a family of transcription factors, essential for T-cell activation. Norisoboldine (NOR), an isoquinoline alkaloid from Radix linderae, has been demonstrated to possess anti-inflammatory activity.
Objective: This study examines NOR’s effect on NFAT activation and its therapeutic potential for atopic dermatitis (AD).
Materials and methods: The transcriptional activity of NFAT was examined with luciferase reporter assay, using K562-luc cells, stimulated with 20 ng/mL PMA plus 1 μM ionomycin. NFAT dephosphorylation was examined by immuno-blotting in K562-luc cells and Jurkat cells. Interleukin-2 (IL-2) expression in Jurkat cells was examined by real-time PCR. A mouse model of dermatitis, induced by 2,4-dinitrochlorobenzene (DNCB), was used to test NOR’s therapeutic potential for AD.
Results: NOR, dose-dependently, inhibited PMA and ionomycin-induced NFAT reporter gene expression in K562-luc cells in the range of 2-50 μM. NOR also inhibited PMA and ionomycin-induced NFAT dephosphorylation in K562-luc cells and Jurkat cells. Consequently, NOR suppressed PMA plus ionomycin-induced IL-2 expression in Jurkat cells. The administration of NOR (10 mg/kg, i.p.), alleviated DNCB-induced dermatitis in mice, by the reduction of ear swelling and attenuation of inflammatory infiltration into ear tissue. Moreover, mRNA levels of INF-γ, TNF-α, IL-4 and IL-6 in ears of NOR-treated mice were reduced by 78.4, 77.8, 72.3 and 73.9%, respectively, compared with untreated controls.
Discussion and conclusion: This study demonstrates that NOR inhibits NFAT activation in T-cells and alleviates AD-like inflammatory reaction in a DNCB-induced dermatitis model, highlighting NOR as a potential therapeutic agent for AD.

Title

Norisoboldine, an Alkaloid From Radix Linderae, Inhibits NFAT Activation and Attenuates 2,4-dinitrofluorobenzene-induced Dermatitis in Mice

Author

Shuang Gao 1 , Wencai Li 1 , Guochao Lin 1 , Guangrong Liu 2 , Wenjuan Deng 2 , Chuntao Zhai 3 , Chunliang Bian 3 , Gaiying He 3 , Zhenlin Hu 1

Publish date

2016 Oct

PMID

25481498

Abstract

Norisoboldine (NOR), the main active ingredient of the dry root of Lindera aggregata, was previously proven to have substantial therapeutic effects on collagen-induced arthritis (CIA) in mice by oral administration. However, it exhibited a very poor bioavailability in normal rats. The pharmacokinetic-pharmacodynamics disconnection attracts us to explore its anti-arthritic mechanism in more detail. In this study, NOR, administered orally, markedly attenuated the pathological changes in CIA rats, which was accompanied by the down-regulation of pro-inflammatory cytokines and the up-regulation of anti-inflammatory cytokine IL-10. Pharmacokinetic studies demonstrated that the plasma concentration of NOR was moderately elevated in CIA rats compared with normal rats, but it was still far lower than the minimal effective concentration required for inhibiting the proliferation and activation of T lymphocytes in vitro. Interestingly, NOR was shown to regulate the balance between Th17 and regulatory T (Treg) cells in the intestinal lymph nodes more strikingly than in other tissues. It could increase the expression of Foxp3 mRNA in both gut and joints, and markedly up-regulate the number of integrin α4β7 (a marker of gut source)-positive Foxp3(+) cells in the joints of CIA rats. These results suggest that the gut might be the primary action site of NOR, and NOR exerts anti-arthritis effect through regulating the balance between Th17 and Treg cells in intestinal lymph nodes and yielding a trafficking of lymphocytes (especially Treg cells) from the gut to joint. The findings of the present study also provide a plausible explanation for the anti-arthritic effects of poorly absorbed compounds like NOR.

KEYWORDS

CIA; Gut-associated lymphoid tissues; Norisoboldine; Regulatory T cell; Th17 cell.

Title

Norisoboldine Ameliorates Collagen-Induced Arthritis Through Regulating the Balance Between Th17 and Regulatory T Cells in Gut-Associated Lymphoid Tissues

Author

Bei Tong 1 , Yannong Dou 1 , Ting Wang 1 , Juntao Yu 1 , Xin Wu 1 , Qian Lu 1 , Guixin Chou 2 , Zhengtao Wang 2 , Lingyi Kong 3 , Yue Dai 4 , Yufeng Xia 5

Publish date

2015 Jan 1