Palmatine

palmatine
Names
IUPAC name
2,3,9,10-Tetramethoxy-5,6-dihydroisoquinolino[2,1-b]isoquinolin-7-ium
Other names
Berbericinine
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
KEGG
UNII
  • InChI=1/C21H25NO4/c1-23-18-6-5-13-9-17-15-11-20(25-3)19(24-2)10-14(15)7-8-22(17)12-16(13)21(18)26-4/h5-6,10-11,17H,7-9,12H2,1-4H3
    Key: AEQDJSLRWYMAQI-UHFFFAOYAT
  • O(c1c4c(ccc1OC)CC3c2c(cc(OC)c(OC)c2)CCN3C4)C
Properties
C21H21NO4+
Molar mass 351.401 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).

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]

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]

Pharmacology

Neuroprotective activity

Palmatine can be used to treat Alzheimer’s disease, mainly by inhibiting the activity of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and neuraminidase-1 (NA-1). It was found, that the positively charged nitrogen on palmatine binds in the gorge of active sire of AChE.[10]

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.[11]

Regulating blood lipid activity

Palmatine achieved hypoglycemic effects by inducing insulin release and insulin-mimicking activity.[12][13] In addition, studies found that palmatine also inhibited the activity of lens aldose reductase,[14] sucrase and maltase.[15] In vivo research showed that palmatine reduced serum total cholesterol (TC) and triglycerides (TG) and increased serum high-density lipoprotein cholesterol.[16]

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.[17] In addition, palmatine also had anti-cancer activity on MCF-7, U251, KB,[18] CHOK-1, HT-29 and SiHacell lines.[19] 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.[20][21][22] 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,[23] and 9-O-substituted palmatine derivatives exhibited stronger antibacterial activity.[24][25]

Anti-inflammatory activity

Studies have shown that palmatine can decrease the production of pro-inflammatory factors and increase the production of anti-inflammatory factors.[26]

Other pharmacological activity

Studies have shown that palmatine chave antioxidant activity,[27][28] had a protective effect on gastric ulcer,[29] derivatives of palmatine were more effective against ulcerative colitis, including low cytotoxicity to intestinal epithelial cells.[30] In addition, palmatine might have the antiarrhythmic effect,[31] and provideprotection from myocardial ischemia-reperfusion injury.[32]

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.[33] However, some 9-O-substituted palmatine derivatives exhibited less toxic than palmatine.[34] In addition, palmatine had higher affinity to nucleic acids than serum proteins, which make them suitable candidates for delivery by serum proteins.[35]

See also

References

  1. ^ Yang, Seong Baek; Kim, Eun Hee; Kim, Seung Hee; Kim, Young Hun; Oh, Weontae; Lee, Jin-Tae; Jang, Young-Ah; Sabina, Yeasmin; Ji, Byung Chul; Yeum, Jeong Hyun (2018-09-17). "Electrospinning Fabrication of Poly(vinyl alcohol)/Coptis chinensis Extract Nanofibers for Antimicrobial Exploits". Nanomaterials. 8 (9): 734. doi:10.3390/nano8090734. ISSN 2079-4991. PMC 6164458. PMID 30227671.
  2. ^ Zhang, Qian; Chen, Cen; Wang, Feng-Qin; Li, Chun-Hong; Zhang, Qi-Hui; Hu, Yuan-Jia; Xia, Zhi-Ning; Yang, Feng-Qing (2016-12-01). "Simultaneous screening and analysis of antiplatelet aggregation active alkaloids from Rhizoma Corydalis". Pharmaceutical Biology. 54 (12): 3113–3120. doi:10.1080/13880209.2016.1211714. ISSN 1388-0209. PMID 27558975.
  3. ^ Kumar, Peeyush; Srivastava, Vartika; Chaturvedi, Rakhi; Sundar, Durai; Bisaria, V. S. (2017-08-01). "Elicitor enhanced production of protoberberine alkaloids from in vitro cell suspension cultures of Tinospora cordifolia (Willd.) Miers ex Hook. F. & Thoms". Plant Cell, Tissue and Organ Culture. 130 (2): 417–426. doi:10.1007/s11240-017-1237-0. ISSN 1573-5044. S2CID 41951538.
  4. ^ Rong, Qian; Xu, Min; Dong, Qi; Zhang, Yuli; Li, Yinglun; Ye, Gang; Zhao, Ling (2016-08-30). "In vitro and in vivo bactericidal activity of Tinospora sagittata (Oliv.) Gagnep. var. craveniana (S.Y.Hu) Lo and its main effective component, palmatine, against porcine Helicobacter pylori". BMC Complementary and Alternative Medicine. 16 (1): 331. doi:10.1186/s12906-016-1310-y. ISSN 1472-6882. PMC 5006617. PMID 27576439.
  5. ^ Sun, Minglong; Xu, Lijiao; Peng, Yingli; Liu, Tong; Zhang, Yuhong; Zhou, Zhiqiang (2016-04-01). "Multiscale analysis of the contents of palmatine in the Nature populations of Phellodendron amurense in Northeast China". Journal of Forestry Research. 27 (2): 265–272. doi:10.1007/s11676-015-0200-3. ISSN 1993-0607. S2CID 15369649.
  6. ^ Xin, Aiyi; Zhang, Yaming; Zhang, Yanxia; Di, Duolong; Liu, Junxi (October 2018). "Development of an HPLC-DAD method for the determination of five alkaloids in Stephania yunnanensis Lo and in rat plasma after oral dose of Stephania yunnanensis Lo extracts". Biomedical Chromatography. 32 (10): e4292. doi:10.1002/bmc.4292. ISSN 1099-0801. PMID 29782649. S2CID 29167917.
  7. ^ Virtanen P., Njimi T., Ekotto Mengata D. (1989). "Clinical trials of hepatitis cure with protoberberine alkaloids of Enantia Chlorantha". Eur. J. Clin. Pharmacol. 36: A123.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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  9. ^ Jia, Fan; Zou, Gang; Fan, Jingjing; Yuan, Zhiming (2010). "Identification of palmatine as an inhibitor of West Nile virus". Archives of Virology. 155 (8): 1325–1329. doi:10.1007/s00705-010-0702-4. PMID 20496087.
  10. ^ Mukherjee, Pulok K.; Kumar, Venkatesan; Mal, Mainak; Houghton, Peter J. (2007-04-10). "Acetylcholinesterase inhibitors from plants". Phytomedicine. 14 (4): 289–300. doi:10.1016/j.phymed.2007.02.002. ISSN 0944-7113. PMID 17346955.
  11. ^ Dhingra, Dinesh; Bhankher, Arun (2014-02-01). "Behavioral and biochemical evidences for antidepressant-like activity of palmatine in mice subjected to chronic unpredictable mild stress". Pharmacological Reports. 66 (1): 1–9. doi:10.1016/j.pharep.2013.06.001. ISSN 1734-1140. PMID 24905299. S2CID 14391622.
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  14. ^ Patel, Mayurkumar B.; Mishra, Shrihari (2012-02-01). "Isoquinoline Alkaloids from Tinospora cordifolia Inhibit Rat Lens Aldose Reductase". Phytotherapy Research. 26 (9): 1342–1347. doi:10.1002/ptr.3721. ISSN 0951-418X. PMID 22294283. S2CID 34663821.
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  16. ^ Ma, Hang; Hu, Yinran; Zou, Zongyao; Feng, Min; Ye, Xiaoli; Li, Xuegang (2016-04-04). "Antihyperglycemia and Antihyperlipidemia Effect of Protoberberine Alkaloids From Rhizoma Coptidis in HepG2 Cell and Diabetic KK-Ay Mice". Drug Development Research. 77 (4): 163–170. doi:10.1002/ddr.21302. ISSN 0272-4391. PMID 27045983. S2CID 31823923.
  17. ^ Zhang, Lei; Li, Jingjing; Ma, Fei; Yao, Shining; Li, Naisan; Wang, Jing; Wang, Yongbin; Wang, Xiuzhen; Yao, Qizheng (2012-09-25). "Synthesis and Cytotoxicity Evaluation of 13-n-Alkyl Berberine and Palmatine Analogues as Anticancer Agents". Molecules. 17 (10): 11294–11302. doi:10.3390/molecules171011294. ISSN 1420-3049. PMC 6268624. PMID 23011273.
  18. ^ Costa, Emmanoel Vilaça; Cruz, Pedro Ernesto O. da; Pinheiro, Maria Lúcia B.; Marques, Francisco A.; Ruiz, Ana Lúcia T. G.; Marchetti, Gabriela M.; Carvalho, João Ernesto de; Barison, Andersson; Maia, Beatriz Helena L. N. S. (2013). "Aporphine and Tetrahydroprotoberberine Alkaloids from the Leaves ofGuatteria friesiana(Annonaceae) and their Cytotoxic Activities". Journal of the Brazilian Chemical Society. doi:10.5935/0103-5053.20130103. ISSN 0103-5053.
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  20. ^ Ali, Daoud; Ali, Huma (2014-07-03). "Assessment of DNA damage and cytotoxicity of palmatine on human skin epithelial carcinoma cells". Toxicological & Environmental Chemistry. 96 (6): 941–950. Bibcode:2014TxEC...96..941A. doi:10.1080/02772248.2014.987510. ISSN 0277-2248. S2CID 84213943.
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  24. ^ Li, ZC; Kong, XB; Mai, WP; Sun, GC; Zhao, SZ (2015). "Synthesis and antimicrobial activity of 9-o-substituted palmatine derivatives". Indian Journal of Pharmaceutical Sciences. 77 (2): 196–201. doi:10.4103/0250-474x.156588. ISSN 0250-474X. PMC 4442469. PMID 26009653.
  25. ^ Song, Li; Zhang, Hai-Jing; Deng, An-Jun; Li, Jia; Li, Xiang; Li, Zhi-Hong; Zhang, Zhi-Hui; Wu, Lian-Qiu; Wang, Sheng-Qi; Qin, Hai-Lin (May 2018). "Syntheses and structure-activity relationships on antibacterial and anti-ulcerative colitis properties of quaternary 13-substituted palmatines and 8-oxo-13-substituted dihydropalmatines". Bioorganic & Medicinal Chemistry. 26 (9): 2586–2598. doi:10.1016/j.bmc.2018.04.025. ISSN 0968-0896. PMID 29680749.
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  33. ^ Ali, Daoud; Ali, Huma (2014-07-03). "Assessment of DNA damage and cytotoxicity of palmatine on human skin epithelial carcinoma cells". Toxicological & Environmental Chemistry. 96 (6): 941–950. Bibcode:2014TxEC...96..941A. doi:10.1080/02772248.2014.987510. ISSN 0277-2248. S2CID 84213943.
  34. ^ Li, ZC; Kong, XB; Mai, WP; Sun, GC; Zhao, SZ (2015). "Synthesis and antimicrobial activity of 9-o-substituted palmatine derivatives". Indian Journal of Pharmaceutical Sciences. 77 (2): 196–201. doi:10.4103/0250-474x.156588. ISSN 0250-474X. PMC 4442469. PMID 26009653.
  35. ^ Khan, Asma Yasmeen; Suresh Kumar, Gopinatha (2015-12-01). "Natural isoquinoline alkaloids: binding aspects to functional proteins, serum albumins, hemoglobin, and lysozyme". Biophysical Reviews. 7 (4): 407–420. doi:10.1007/s12551-015-0183-5. ISSN 1867-2469. PMC 5418488. PMID 28510102.