| Description: |
Protopine acts as a potent inhibitor of thromboxane synthesis and PAF with hepatoprotective, antidepressant, antioxidant, antispasmodic and relaxant properties. Protopine is also a novel microtubule-stabilizing agent, causes mitotic arrest and apoptotic cell death in human hormone-refractory prostate cancer cell lines. Protopine blocks phosphorylation of mitogen-activated protein kinases (MAP kinases) and also blocks activation of a nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). |
| Targets: |
COX | EGFR | Integrin | Calcium Channel | Caspase | NF-kB | 5-HT Receptor | CDK | Bcl-2/Bax | PGE | NO |
| In vitro: |
| Afr. J. Tradit. Complement. Altern. Med., 2014 Jan 28;11(2):415-24. | | Protopine inhibits heterotypic cell adhesion in MDA-MB-231 cells through down-regulation of multi-adhesive factors.[Pubmed: 25435628] | A Chinese herb Corydalis yanhusuo W.T. Wang that showed anticancer and anti-angiogenesis effects in our previous studies was presented for further studies. In the present study, we studied the anticancer proliferation and adhesion effects of five alkaloids which were isolated from Corydalis yanhusuo.
METHODS AND RESULTS:
MTT dose response curves, cell migration assay, cell invasion assay, as well as three types of cell adhesive assay were performed on MDA-MB-231 human breast cancer cells. The mechanism of the compounds on inhibiting heterotypic cell adhesion were further explored by determining the expression of epidermal growth factor receptor (EGFR), Intercellular adhesion molecule 1 (ICAM-1), αv-integrin, β1-integrin and β5-integrin by western blotting assay.
In five tested alkaloids, only protopine exhibited anti-adhesive and anti-invasion effects in MDA-MB-231 cells, which contributed to the anti-metastasis effect of Corydalis yanhusuo. The results showed that after treatment with protopine for 90 min, the expression of EGFR, ICAM-1, αv-integrin, β1-integrin and β5-integrin were remarkably reduced.
CONCLUSIONS:
The present results suggest that protopine seems to inhibit the heterotypic cell adhesion between MDA-MB-231 cells, and human umbilical vein endothelial cells by changing the expression of adhesive factors. |
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| In vivo: |
| Pharmacol Res. 1997 Jul;36(1):1-7. | | Anti-thrombotic and anti-inflammatory activities of protopine.[Pubmed: 9368908 ] |
METHODS AND RESULTS:
The effects of protopine on human platelet aggregation and arachidonic acid (AA) metabolism via cyclooxygenase (COX) and lipoxygenase (LOP) enzymes were examined. Platelet aggregation induced by various platelet agonists (AA, ADP, collagen and PAF) was strongly inhibited by protopine in a concentration-related manner. The IC50 values (microM) of protopine (mean +/- SEM) against: AA; 12 +/- 2: ADP; 9 +/- 2: collagen; 16 +/- 2 and PAF; 11 +/- 1, were much less than those observed for aspirin. In addition, protopine selectively inhibited the synthesis of thromboxane A2 (TXA2) via COX pathway and had no effect on the LOP pathway in platelets. In vivo, pretreatment with protopine (50-100 mg kg-1) protected rabbits from the lethal effects of AA (2 mg kg-1) or PAF (11 micrograms kg-1) in dose-dependent fashion. Protopine (50-100 mg kg-1) also inhibited carrageenan-induced rat paw oedema with a potency of three-fold as compared to aspirin.
CONCLUSIONS:
These results are suggestive that protopine acts as a potent inhibitor of thromboxane synthesis and PAF with anti-inflammatory properties. | | Phytomedicine. 2008 Jun;15(6-7):470-7. | | Hepatoprotective potential of Fumaria indica Pugsley whole plant extracts, fractions and an isolated alkaloid protopine.[Pubmed: 18164606 ] |
METHODS AND RESULTS:
The present investigation demonstrates the hepatoprotective potential of 50% ethanolic water extract of whole plant of Fumaria indica and its three fractions viz., hexane, chloroform and butanol against d-galactosamine induced hepatotoxicity in rats. The hepatoprotection was assessed in terms reduction in histological damage, changes in serum enzymes (SGOT, SGPT, ALP) and metabolites bilirubin, reduced glutathione (GSH) and lipid peroxidation (MDA content). Among fractions more than 90% protection was found with butanol fraction in which alkaloid protopine was quantified as highest i.e. about 0.2mg/g by HPTLC. The isolated protopine in doses of 10-20mg p.o. also proved equally effective hepatoprotectants as standard drug silymarine (single dose 25mg p.o.).
CONCLUSIONS:
In general all treatments excluding hexane fraction proved hepatoprotective at par with silymarine (p | | Planta Med. 1998 Dec;64(8):758-60. | | Antispasmodic and relaxant activity of chelidonine, protopine, coptisine, and Chelidonium majus extracts on isolated guinea-pig ileum.[Pubmed: 9933996 ] |
METHODS AND RESULTS:
Two ethanolic dry extracts from the herb Chelidonium majus L. with a defined content of the main alkaloids (chelidonine, protopine, and coptisisine) and the alkaloids themselves were studied in three different antispasmodic test models on isolated ileum of guinea-pigs. In the BaCl2-stimulated ileum, chelidonine and protopine exhibited the known papaverine-like musculotropic action, whereas coptisine (up to 3.0 x 10(-5) g/ml) was ineffective in this model. Both extracts were active with 53.5% and 49.0% relaxation at 5 x 10(-4) g/ml. The carbachol and the electric field stimulated contractions were antagonized by all three alkaloids. Coptisine showed competitive antagonist behaviour with a pA2 value of 5.95. Chelidonine and protopine exhibited a certain degree of non-competitive antagonism.
CONCLUSIONS:
In the electric field the antagonist activities decreased in the order protopine > coptisine > chelidonine.
The concentrations of the chelidonium herb extracts for 50% inhibition of the carbachol and electrical field induced spasms were in the range of 2.5 to 5 x 10(-4) g/ml. |
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