Palmatine
Chemical compound
From Wikipedia, the free encyclopedia
Palmatine is a protoberberine alkaloid found in several plants including Coptis chinensis[1] (Rhizoma coptidis, chinese goldthread), Corydalis yanhusuo,[2] Tinospora cordifolia[3] (gurjo, heart-leaved moonseed), Tinospora sagittata,[4] Phellodendron amurense[5] (amur cork tree), and Stephania yunnanensis.[6]
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| Names | |
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| IUPAC name
2,3,9,10-Tetramethoxy-5,6-dihydroisoquinolino[2,1-b]isoquinolin-7-ium | |
| Other names
Berbericinine | |
| Identifiers | |
3D model (JSmol) |
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| ChEMBL | |
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| KEGG | |
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| UNII | |
CompTox Dashboard (EPA) |
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| Properties | |
| C21H22NO4+ | |
| Molar mass | 352.409 g·mol−1 |
| Density | 1.23 g/cm3 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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It is the major component of the protoberberine extract from Enantia chlorantha.[7][better source needed]
It has been studied for its potential use in the treatment of jaundice, dysentery, hypertension, inflammation, and liver-related diseases.[8] This compound also has weak in vitro activity against flavivirus.[9]
Biosynthesis
The biosynthesis of palmatine starts with tyrosine and proceeds via (S)-reticuline in a pathway leading to benzylisoquinoline alkaloids.[10][11] The final step is catalysed by the enzyme tetrahydroberberine oxidase, which oxidises tetrahydropalmatine:[12][13]
Alternatively, a methylation reaction catalysed by columbamine O-methyltransferase produces palmatine from columbamine. The methyl group comes from the cofactor, S-adenosyl methionine (SAM). This enzyme was characterised from Berberis wilsoniae.[14]
Metabolism
In Corydalis cava, palmatine is converted to corydaline by the enzyme corydaline synthase. The methyl group comes from SAM and the reaction also requires nicotinamide adenine dinucleotide phosphate (NADPH).[15]
Pharmacology
Neuroprotective activity
Palmatine is an inhibitor of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and neuraminidase-1 (NA-1), and has potential applications in the therapy of Alzheimer's disease. It was found that the positively charged nitrogen on palmatine binds in the gorge of active sire of AChE.[16][better source needed]
Research show that palmatine had antidepressant effect. It was achieved by regulating brain catalase levels, monoamine oxidase-A (MAO-A) activity, lipid peroxidation, plasma nitrite and corticosterone levels.[17]
Regulating blood lipid activity
Palmatine achieved hypoglycemic effects by inducing insulin release and insulin-mimicking activity.[18][19] In addition, studies found that palmatine also inhibited the activity of lens aldose reductase,[20] sucrase and maltase.[21] In vivo research showed that palmatine reduced serum total cholesterol (TC) and triglycerides (TG) and increased serum high-density lipoprotein cholesterol.[22]
Anticancer activity
Research showed that palmatine had broad anti-cancer activity. Palmatine had significant growth inhibitory effects on seven human cancer cell lines: 7701QGY, SMMC7721, HepG2, CEM, CEM/VCR, K III and Lewis.[23] In addition, palmatine also had anti-cancer activity on MCF-7, U251, KB,[24] CHOK-1, HT-29 and SiHacell lines.[25] Palmatine induced apoptosis in human skin epithelial carcinoma cells (A431) in a concentration- and time-dependent manner via damaging severely to DNA and inhibiting the activity of Bcl-2 protein.[26][27][28] In addition, palmatine can inhibit the proliferation and infiltration of cancer cells.
Antibacterial and antiviral activity
Palmitine has inhibitory effect on Gram-positive bacteria which is significantly stronger than that on Gram-negative bacteria,[29] and 9-O-substituted palmatine derivatives exhibited stronger antibacterial activity.[30][31]
Anti-inflammatory activity
Studies have shown that palmatine can decrease the production of pro-inflammatory factors and increase the production of anti-inflammatory factors.[32]
Other pharmacological activity
Studies have shown that palmatine chave antioxidant activity,[33][34] had a protective effect on gastric ulcer,[35] derivatives of palmatine were more effective against ulcerative colitis, including low cytotoxicity to intestinal epithelial cells.[36] In addition, palmatine might have the antiarrhythmic effect,[37] and provideprotection from myocardial ischemia-reperfusion injury.[38]
Toxicity
A large number of studies have shown that palmatine has a complex effect on the metabolism of enzymes in the liver, and that palmatine has significant DNA toxicity.[39] However, some 9-O-substituted palmatine derivatives exhibited less toxic than palmatine.[40] In addition, palmatine had higher affinity to nucleic acids than serum proteins, which make them suitable candidates for delivery by serum proteins.[41]