Honokiol

Source: Wikipedia, the free encyclopedia.
Honokiol
Names
Preferred IUPAC name
3′,5-Di(prop-2-en-1-yl)[1,1′-biphenyl]-2,4′-diol
Other names
houpa, hnk
Identifiers
3D model (
JSmol
)
ChEMBL
ChemSpider
ECHA InfoCard
 100.122.079 Edit this at Wikidata
KEGG
UNII
  • InChI=1S/C18H18O2/c1-3-5-13-7-9-18(20)16(11-13)14-8-10-17(19)15(12-14)6-4-2/h3-4,7-12,19-20H,1-2,5-6H2 checkY
    Key: FVYXIJYOAGAUQK-UHFFFAOYSA-N checkY
  • InChI=1/C18H18O2/c1-3-5-13-7-9-18(20)16(11-13)14-8-10-17(19)15(12-14)6-4-2/h3-4,7-12,19-20H,1-2,5-6H2
    Key: FVYXIJYOAGAUQK-UHFFFAOYAL
  • Oc1ccc(cc1C/C=C)c2cc(ccc2O)C\C=C
Properties
C18H18O2
Molar mass 266.334 g/mol
Appearance White solid
sparingly (25 °C)
Related compounds
Related biphenols
 diethylstilbestrol,
dihydroxyeugenol
Related compounds
 magnolol.
4-O-Methylhonokiol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Honokiol is a

4-O-methylhonokiol, and obovatol
.

Biology

Honokiol has been extracted from a number of species of Magnolia native to many regions of the globe. Magnolia grandiflora, which is native to the American South, as well as Mexican species like Magnolia dealbata have been found to be sources of honokiol.[1] Traditionally in Asian medicine, the Magnolia biondii, Magnolia obovata, and Magnolia officinalis are commonly used.[2] The compound itself has a spicy odor.

Because of its physical properties, honokiol can readily cross the

blood brain barrier and the blood-cerebrospinal fluid barrier.[1][3] As a result, honokiol is a potentially potent therapy with high bioavailability
.

Chemistry

Structure

Honokiol belongs to a class of neolignan biphenols. As a polyphenol it is relatively small and can interact with cell membrane proteins through intermolecular interactions like

aromatic pi orbital co-valency.[1] It is hydrophobic and readily dissolved in lipids. It is structurally similar to propofol.[1]

Purification

There are several methods for purifying and isolating honokiol. In nature, honokiol exists with its structural isomer

silica.[4]

Figure 1

Magnolol and Honokiol are normally inseparable. Honokiol is easily separable from the protected magnolol acetonide

Additionally a rapid separation approach was published in the Journal of Chromatography A in 2007. The process uses high-capacity high-speed countercurrent chromatography (high-capacity HSCCC).[5] Through this method honokiol can be separated and purified to above 98% purity with a high yield in under an hour.

History

Traditional medicine

Seed Cone

Extracts from the bark or seed cones of the Magnolia tree have been widely used in traditional medicine in China, Korea, and Japan.[2]

Magnolia bark has traditionally been used in Eastern medicine as analgesic and to treat anxiety and mood disorders.[2][6] In traditional Chinese medicine, magnolia bark is called Houpu and is most commonly taken from two species, Magnolia obovata and Magnolia officinalis.[7] Some Chinese traditional formulas containing Houpu include Banxia Houpu Tang (半夏厚朴丸), Xiao Zhengai Tang, Ping Wei San(平胃散) and Shenmi Tang.[2] Japanese Kampo formulas include, Hange-koboku-to (半夏厚朴湯) and Sai-boku-to (柴朴湯).[2][6]

Seeds

Western medical research

Honokiol is a

gastrointestinal system. It has been shown to have antitumorigenic, anti-inflammatory, and antioxidant effects as well.[1][8][9]

Side effects and contraindications

Research has shown a limited side effect profile for honokiol, and it appears to be well tolerated. However, its antithrombotic effects could cause hemorrhage especially in patients with conditions that would put them at a higher risk like

hemophilia or Von Willebrand disease.[1] Additionally, patients already taking anticoagulants should talk to their doctor before taking honokiol supplements. In a 2002 study, researchers induced cell death in fetal rat cortical neurons by directly applying 100μM in vitro.[10]

Pharmacology

Antitumorigenic activities

Honokiol has shown pro-

T cells.[17]

Neurotrophic activity

Honokiol [

4-O-methylhonokiol was shown to be a potent and selective cannabinoid CB2 receptor inverse agonist and to possess antiosteoclastic effects.[18]

Antithrombotic activity

Honokiol inhibits platelet aggregation in rabbits in a dose-dependent manner, and protects cultured RAEC against oxidized low density lipoprotein injury. Honokiol significantly increases the prostacyclin metabolite 6-keto-PGF1alpha, potentially the key factor in honokiol's antithrombotic activity.[19]

Anti-inflammatory activity

Studies examining honokiol as a protective therapy against

RANTES/CCL5.[21]

Antioxidant activity

Honokiol has also been proposed as an antioxidant. The compound protects against lipid peroxidation by interfering with ROS production and migration.[20] Accumulation of ROS extracellularly causes macromolecular damage while intracellular accumulation may induce cytokine activation.

Cytotoxicity inhibition

One way that honokiol acts as a neuroprotective is through cellular regulation and subsequent inhibition of cytotoxicity. Two mechanisms used to achieve this inhibition are GABAA Modulation and Ca2+ Inhibition. Cytotoxicity inhibition may be the neuroprotective mechanism of honokiol. Honokiol has also been shown to inhibit repetitive firing by blocking

glutamate.[23]

GABAA modulation
GABAA receptor binding sites

It is believed that honokiol acts on

Z-drugs. However, honokiol has been shown to achieve anxiolysis with fewer motor or cognitive side effects than GABAA receptor agonists such as flurazepam and diazepam. It has been shown that honokiol likely has a higher selectivity for different GABAA receptor subtypes and both magnolol and honokiol showed higher efficacy when acting on receptors containing δ subunits.[1]
GABAA receptors control ligand-gated Cl− channels that can help increase seizure thresholds through the influx of chloride anions. Honokiol may also affect the synthesis of
hippocampal levels of glutamate decarboxylase (GAD67) an enzyme that catalyzes the synthesis of GABA. However, the increase was within the margin of error for the method used to quantify the protein.[24]

Ca2+ inhibition

A high concentration of Ca2+ induces

G-protein pathways.[20]

Antiviral activity

Honokiol has been shown to inhibit

human immunodeficiency virus (HIV-1).[4]

Metabolic activity

Honokiol was shown to normalize blood glucose levels and prevent body weight gain in diabetic mice by acting as agonist of PPARgamma.[26]

Pharmacokinetics

The pharmacokinetics of honokiol have been explored in rats and mice; however, further research must be done in humans.[27] Intravenous delivery of 5–10 mg/kg in rodent models has shown a plasma half-life of around 40–60 minutes while intraperitoneal injections of 250 mg/kg had a plasma half-life around 4–6 hours with maximum plasma concentration occurring between 20 and 30 minutes.[1][28]

Delivery methods

Honokiol is most commonly taken orally. There are a number of supplements available containing honokiol. Magnolia tea made from the bark of the tree is also a common delivery method of honokiol.[citation needed] Both Native Americans and Japanese medicine use tea gargles to treat toothaches and sore throats.[29] Because honokiol is highly hydrophobic it must be dissolved in a lipid for many delivery methods. In many current animal studies the compound is dissolved in a lipid emollient and delivered through intraperitoneal injection. There is ongoing[when?] work developing liposomal emulsions for IV delivery.[27]

References

  1. ^
    PMID 2406271
    .
  2. ^
    PMID 21277893
    .
  3. PMID 21559510
    .
  4. ^
    PMID 16722664
    .
  5. PMID 17222860
    .
  6. ^
    S2CID 207485984
    .
  7. PMID 9461663
    .
  8. PMID 19203212
    .
  9. S2CID 30716241
    .
  10. ^
    PMID 11934579
    .
  11. PMID 21449214
    .
  12. PMID 24179537
    .
  13. S2CID 22184445
    .
  14. PMID 15870175
    .
  15. PMID 15802533
    .
  16. PMID 12816951
    .
  17. PMID 19483651
    .
  18. PMID 21867920
    .
  19. PMID 16115372
    .
  20. ^
    S2CID 44974515
    .
  21. ^
    S2CID 10051483
    .
  22. PMID 20192217
    .
  23. PMID 16631734
    .
  24. PMID 21561750
    .
  25. S2CID 22428079
    .
  26. PMID 23811337
    .
  27. ^
    PMID 23444779
    .
  28. PMID 8061832
    .
  29. ISBN 978-1-57912-392-5
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Honokiol&oldid=1193911340"