Pharmacological effects
- Tripterine is a natural product with a variety of biological activity. It has a strong antioxidant effect, anti-cancer neovascularization effect as well as anti-rheumatoid effect. It is mainly isolated from the root bark of the celastraceae plant, Tripterygium wilfordii. It is one of the active ingredients contained in the rheumatoid-treatment drug Tripterygium tablet, Tripterygium Glycosides tablets and other preparations.
- The major activity and pharmacological effects of Tripterine:
- Cytotoxic activity. In vitro, it has non-specific cytotoxic activity against P388 and a group of human cancer cell lines.
- Immune regulation. It could significantly inhibit the formation of hemolytic plaque cells in mouse spleen cells and significantly inhibit the mice delayed-type hypersensitivity.
- Anti-inflammatory effect. At a dose of 0.5mg/kg, it could result in significant inhibition of the formation of rat cotton granuloma. At a dose of 0.1~1.0μg/mL, it could suppress the production of PGE2 induced by the yeast sugar; at a dose of 1.0μg/mL, it can inhibit the macrophage phagocytosis.
- The anti-oxidation effect of tripterine is 15 times that of tocopherol with an IC50 of 7μM. Inhibit the peroxidation occurring inside and outside of the mitochondrial membrane, direct removing the free radicals.
- Tripterine can extend the sleep time of mice triggered by the pentobarbital sodium.
- Immunosuppressive effect: inhibit the spleen cell proliferation of mice induced by PHA, ConA and LPS, further inhibiting the lymphocyte proliferation.
- It can inhibit the in vitro sperm fertilization capacity of guinea pig with the activity being significantly stronger than acetic acid gossypol.
- Anti-arthritic effect, it will inhibit the activity of interleukin-1 of inside and outside the mouse intraperitoneal macrophages, inhibit the production of interleukin-2 by mouse spleen cells and lower the level of PGE2 produced by rabbit synovial cells.
Source: ChemicalBook Editorial.
Application
Celastrol is an effective proteasome inhibitor. It has been confirmed that it is capable of inducing apoptosis of cancer cells through inhibiting proteasome activity.
Description
Celastrol (34157-83-0) displays potent antioxidant and anti-inflammatory activity. Inhibits NFkB (IC50=270 nM). It induces heat shock response and cytoprotection in various cells. Inhibits 20S proteasome chymotrypsin activity (IC50=2.5 mM). Induces autophagy by targeting AR/miR-101 in prostate cancer cells.4 Induces UPR-dependent cell death in cancer cells.5 Cell permeable.
Chemical Properties
Orange Red Solid
Uses
antineoplastic, NO synthesis inhibitor, chaperone stimulant
Uses
Celastrol is an antioxidant natural product which inhibits the growth of human glioma xenografts in nude mice through suppressing VEGFR expression. Used for clinical treatment for rheumatoid arthritis, was demonstrated to have antiangiogenic activity, and be inhibitory against mice tumor growth by a few recent studies. Celastrol also has been shown to have the power to kill tumor cells and can work as an anticarcinogen. It is also a leptin sensitizer with the potential to reduce weight in obesity.
Uses
Celastrol can be used as an antioxidant onstrated to have antiangiogenic activity, and be inhibitory against mice tumor growth by a few recent studies.
Uses
An antioxidant natural product Celastrol inhibits the growth of human glioma xenografts in nude mice through suppressing VEGFR expression. Used for clinical treatment for rheumatoid arthritis, was demonstrated to have antiangiogenic activity, and be
Definition
ChEBI: A pentacyclic triterpenoid that is 24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid bearing an oxo substituent at position 2, a hydroxy substituent at position 3 and two methyl groups at positions 9 and 13. An antioxidant and anti-inflammatory agent.
otently inhibits lipid peroxidation in mitochondria and inhibits TNF-alpha-induced NFkappaB activation. Also shown to inhibit topoisomerase II activity in vitro (IC50 = 7.41 muM).
General Description
This substance is a primary reference substance with assigned absolute purity (considering chromatographic purity, water, residual solvents, inorganic impurities). The exact value can be found on the certificate. Produced by PhytoLab GmbH & Co. KG
Biological Activity
Antioxidant and anti-inflammatory agent. Potently inhibits lipid peroxidation in mitochondria and inhibits TNF- α -induced NF κ B activation. Also shown to inhibit topoisomerase II activity in vitro (IC 50 = 7.41 μ M).
Biochem/physiol Actions
Celastrol is a potent antioxidant, and anti-inflammatory agent. It is a novel HSP90 inhibitor (disrupts Hsp90/Cdc37 complex), that exhibits anticancer (anti-angiogenic - suppresses VEGFR expression); antioxidant (inhibits lipid peroxidation) and anti-inflammatory activity (suppresses iNOS and inflammatory cytokine production).
Synthesis
Celastrol can be prepared by two methods: total chemical synthesis and biosynthesis. The first is the first total chemical synthesis by Camelio et al. (2015), which starts from 2,3-dimethylbutadiene (with a vanillyl-alcohol-derived stannane fragment) and proceeds in ~31 steps: after building a triene precursor via LDA/MeLi/HWE/Wittig transformations, a non-biomimetic FeCl₃-mediated polyene cyclization (38%, gram scale) constructs the pentacyclic core; E-ring functionalization (6 steps, 38%), Jones oxidation and selenoxide elimination install the Δ8,9 alkene to give wilforol A, which upon benzylation, LiAlH₄ reduction, Et₃SiH/TFA ionic reduction and Pd/C hydrogenation followed by air oxidation (75%) affords racemic celastrol—this route is long with a low overall yield and is not industrially viable [6][7].
The second is the biotechnological route of Zhao et al. (2023): starting from table sugar, engineered yeast (expressing TwOSC1, CYP712K1, CYP716C52, CYP81AM1; intermediate titre up to 15.3 mg/L) produces the key intermediate celastrogenic acid (10) through the mevalonate pathway; 10 is then converted into celastrol by heating in MeOH at 60 °C for one week via a non-enzymatic spontaneous oxidation–decarboxylation–aromatization and catechol-oxidation cascade, giving 21.4% conversion—a greener and scalable production method [8].
References
[1] GAUTAM SETHI. Celastrol, a novel triterpene, potentiates TNF-induced apoptosis and suppresses invasion of tumor cells by inhibiting NF-kappaB-regulated gene products and TAK1-mediated NF-kappaB activation.[J]. Blood, 2007, 109 7: 2727-2735. DOI:
10.1182/blood-2006-10-050807[2] SANDY D WESTERHEIDE. Celastrols as inducers of the heat shock response and cytoprotection.[J]. The Journal of Biological Chemistry, 2004, 279 53: 56053-56060. DOI:
10.1074/jbc.m409267200[3] HUANJIE YANG. Celastrol, a triterpene extracted from the Chinese “Thunder of God Vine,” is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice.[J]. Cancer research, 2006, 66 9: 4758-4765. DOI:
10.1158/0008-5472.can-05-4529[4] JIANQUAN GUO. Celastrol Induces Autophagy by Targeting AR/miR-101 in Prostate Cancer Cells.[J]. PLoS ONE, 2015: e0140745. DOI:
10.1371/journal.pone.0140745[5] ANDREW M. FRIBLEY . Celastrol induces unfolded protein response-dependent cell death in head and neck cancer[J]. Experimental cell research, 2015, 330 2: Pages 412-422. DOI:
10.1016/j.yexcr.2014.08.014[6]
Camelio, A. M., Johnson, T. C., Siegel, D. (2015). Total Synthesis of Celastrol, Development of a Platform to Access Celastroid Natural Products. Journal of the American Chemical Society, 137(37), 11864–11867.
https://doi.org/10.1021/jacs.5b06261[7]
Lu, Y., Liu, Y., Zhou, J., Li, D., Gao, W. (2020). Biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of the quinone‐methide triterpenoid celastrol. Medicinal Research Reviews, 41(2), 1022–1060.
https://doi.org/10.1002/med.21751[8]
Zhao, Y., Hansen, N. L., Duan, Y.-T., Prasad, M., Motawia, M. S., Møller, B. L., Pateraki, I., Staerk, D., Bak, S., Miettinen, K., Kampranis, S. C. (2023). Biosynthesis and biotechnological production of the anti-obesity agent celastrol. Nature Chemistry, 15(9), 1236–1246.
https://doi.org/10.1038/s41557-023-01245-7
