Jump to content

Bilobalide: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous edit
Content deleted Content added
VisualWikitext
Monkbot (talk | contribs)
Bots
3,695,952 edits
m Task 18 (cosmetic): eval 4 templates: del empty params (1×);
Citation bot (talk | contribs)
Bots
5,409,949 edits
Alter: journal, title, template type. Add: chapter-url, series, chapter. Removed or converted URL. Removed parameters. Some additions/deletions were parameter name changes. | Use this bot. Report bugs. | Suggested by Headbomb | Linked from Wikipedia:WikiProject_Academic_Journals/Journals_cited_by_Wikipedia/Maintenance/Misspellings | #UCB_webform_linked 29/226
 
(19 intermediate revisions by 14 users not shown)
Line 1: Line 1:
{{short description|Chemical compound}}
{{Drugbox
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Verifiedfields = changed
| Verifiedfields = changed
| verifiedrevid = 445249903
| verifiedrevid = 445249903
Line 10: Line 12:
| tradename =
| tradename =
| legal_status = legal
| legal_status = legal
| routes_of_administration = oral
| routes_of_administration = [[Oral administration|By mouth]]


<!--Identifiers-->
<!--Identifiers-->
Line 35: Line 37:
}}
}}


'''Bilobalide''' is a biologically active [[terpenoid|terpenic]] tri[[lactone]] present in ''[[Ginkgo biloba]]''.<ref name="pmid19195661">{{cite journal |vauthors=van Beek TA, Montoro P |year=2009 |title=Chemical analysis and quality control of Ginkgo biloba leaves, extracts, and phytopharmaceuticals |journal=[[Journal of Chromatography A]] |volume=1216 |issue=11 |pages=2002–32 |pmid=19195661 |doi=10.1016/j.chroma.2009.01.013}}</ref>
'''Bilobalide''' is a biologically active [[terpenoid|terpenic]] tri[[lactone]] present in ''[[Ginkgo biloba]]''.<ref name="pmid19195661">{{cite journal | vauthors = van Beek TA, Montoro P | title = Chemical analysis and quality control of Ginkgo biloba leaves, extracts, and phytopharmaceuticals | journal = Journal of Chromatography A | volume = 1216 | issue = 11 | pages = 2002–2032 | date = March 2009 | pmid = 19195661 | doi = 10.1016/j.chroma.2009.01.013 }}</ref>


==Chemistry==
==Chemistry==
Line 41: Line 43:


==Biosynthesis==
==Biosynthesis==
Bilobalide and ginkgolide have similar biosynthetic pathways. Bilobalide is formed by partially degraded ginkgolide. Bilobalide is derived from [[geranylgeranyl pyrophosphate]] (GGPP), which is formed by addition of [[farnesyl pyrophosphate]] (FPP) to an [[isopentenyl pyrophosphate]] (IPP) unit to form a C<sub>15</sub> [[sesquiterpene]]. Such formation went through the [[mevalonate pathway]] (MVA) and [[methylerythritol phosphate]] MEP pathway. In order to generate bilobalide, C<sub>20</sub> ginkgolide 13 must form first. To transform from GGPP to abietenyl cation 5, a single bifunctional enzyme [[abietadiene synthase]] E1 is required. However, due to the complexity of ginkgolide structures for rearrangement, ring cleavage, and formation of lactone rings, diterpene 8 is used to explain instead. Levopimaradiene 6 and abietatriene 7 are precursors for ginkgolide and bilobalide formation. The unusual tert-butyl substituent is formed from A ring cleavage in 9. Bilobalide 13 then formed in loss of carbons through degradation from ginkgolide 12, and lactones are formed from residual carboxyl and alcohol functions. The end product of bilobalide contains sesquiterpenes and three lactones units.<ref>Dewick, P. M. Medicinal Natural Products: Products:A Biosynthetic Approach. Third Edition ed.; Wiley&Sons: West Sussex, England, 2009; p 230-232.</ref>
Bilobalide and ginkgolide have similar biosynthetic pathways. Bilobalide is formed by partially degraded ginkgolide. Bilobalide is derived from [[geranylgeranyl pyrophosphate]] (GGPP), which is formed by addition of [[farnesyl pyrophosphate]] (FPP) to an [[isopentenyl pyrophosphate]] (IPP) unit to form a C<sub>15</sub> [[sesquiterpene]]. Such formation went through the [[mevalonate pathway]] (MVA) and [[methylerythritol phosphate]] MEP pathway. In order to generate bilobalide, C<sub>20</sub> ginkgolide 13 must form first. To transform from GGPP to abietenyl cation 5, a single bifunctional enzyme [[abietadiene synthase]] E1 is required. However, due to the complexity of ginkgolide structures for rearrangement, ring cleavage, and formation of lactone rings, diterpene 8 is used to explain instead. Levopimaradiene 6 and abietatriene 7 are precursors for ginkgolide and bilobalide formation. The unusual tert-butyl substituent is formed from A ring cleavage in 9. Bilobalide 13 then formed in loss of carbons through degradation from ginkgolide 12, and lactones are formed from residual carboxyl and alcohol functions. The end product of bilobalide contains sesquiterpenes and three lactones units.<ref>{{cite book | vauthors = Dewick PM | title = Medicinal Natural Products: Products: A Biosynthetic Approach. | edition = Third | publisher = Wiley&Sons | location = West Sussex, England | date = 2009 | pages = 230–232 | isbn = 978-0-470-74168-9 }}</ref>


[[Image:Bilobalide biosynthesis mechanism.JPG|700px|Biosynthesis mechanism of Bilobalide.]]
[[Image:Bilobalide biosynthesis mechanism.JPG|700px|Biosynthesis mechanism of Bilobalide.]]


==Pharmacology==
==Pharmacology==
Bilobalide is important for producing several of the effects of ''Gingko biloba'' extracts, and it has neuroprotective effects,<ref name="pmid12457632">{{cite journal |author=Defeudis FV |year=2002 |title=Bilobalide and neuroprotection |journal=[[Pharmacological Research]] |volume=46 |issue=6 |pages=565–8 |pmid=12457632 |doi=10.1016/S1043-6618(02)00233-5}}</ref><ref name="pmid18325484">{{cite journal |vauthors=Kiewert C, Kumar V, Hildmann O, Hartmann J, Hillert M, Klein J |year=2008 |title=Role of glycine receptors and glycine release for the neuroprotective activity of bilobalide |journal=[[Brain Research]] |volume=1201 |pages=143–50 |pmid=18325484 |doi=10.1016/j.brainres.2008.01.052}}</ref> as well as inducing the liver enzymes CYP3A1 and 1A2,<ref name="pmid18421621">{{cite journal |vauthors=Deng Y, Bi HC, Zhao LZ, He F, Liu YQ, Yu JJ, Ou ZM, Ding L, Chen X, Huang ZY, Huang M, Zhou SF |year=2008 |title=Induction of cytochrome P450s by terpene trilactones and flavonoids of the Ginkgo biloba extract EGb 761 in rats |journal=[[Xenobiotica]] |volume=38 |issue=5 |pages=465–81 |pmid=18421621 |doi=10.1080/00498250701883233}}</ref> which may be partially responsible for interactions between gingko and other herbal medicines or pharmaceutical drugs. Bilobalide has recently been found to be a [[negative allosteric modulator]] at the [[GABAA receptor|GABA<sub>A</sub>]] and [[GABAA-rho receptor|GABA<sub>A</sub>-rho receptors]].<ref>http://sydney.edu.au/medicine/pharmacology/adrien-albert/images/pdfs/RefsPDFs/376.pdf</ref> Of GABA<sub>A</sub>, it may possibly be selective for the subunits predominantly implicated in cognitive and memory functioning such as [[GABRA1|α1]]{{Citation needed|date=December 2014}}.
Bilobalide is important for producing several of the effects of ''Ginkgo biloba'' extracts, and it has neuroprotective effects,<ref name="pmid12457632">{{cite journal | vauthors = Defeudis FV | title = Bilobalide and neuroprotection | journal = Pharmacological Research | volume = 46 | issue = 6 | pages = 565–568 | date = December 2002 | pmid = 12457632 | doi = 10.1016/S1043-6618(02)00233-5 }}</ref><ref name="pmid18325484">{{cite journal | vauthors = Kiewert C, Kumar V, Hildmann O, Hartmann J, Hillert M, Klein J | title = Role of glycine receptors and glycine release for the neuroprotective activity of bilobalide | journal = Brain Research | volume = 1201 | pages = 143–150 | date = March 2008 | pmid = 18325484 | doi = 10.1016/j.brainres.2008.01.052 | s2cid = 5191088 }}</ref> as well as inducing the liver enzymes CYP3A1 and [[CYP1A2]],<ref name="pmid18421621">{{cite journal | vauthors = Deng Y, Bi HC, Zhao LZ, He F, Liu YQ, Yu JJ, Ou ZM, Ding L, Chen X, Huang ZY, Huang M, Zhou SF | title = Induction of cytochrome P450s by terpene trilactones and flavonoids of the Ginkgo biloba extract EGb 761 in rats | journal = Xenobiotica; the Fate of Foreign Compounds in Biological Systems | volume = 38 | issue = 5 | pages = 465–481 | date = May 2008 | pmid = 18421621 | doi = 10.1080/00498250701883233 | s2cid = 84019088 }}</ref> which may be partially responsible for interactions between ginkgo and other herbal medicines or pharmaceutical drugs. Bilobalide has recently been found to be a [[negative allosteric modulator]] at the [[GABAA receptor|GABA<sub>A</sub>]] and [[GABAA-rho receptor|GABA<sub>A</sub>-rho receptors]].<ref>{{cite book | vauthors = Johnston GA, Hanrahan JR, Chebib M, Duke RK, Mewett KN | title = GABA | chapter = Modulation of ionotropic GABA receptors by natural products of plant origin | series = Advances in Pharmacology | volume = 54 | pages = 285–316 | date = 2006 | pmid = 17175819 | doi = 10.1016/s1054-3589(06)54012-8 | publisher = Elsevier | isbn = 978-0-12-032957-1 | chapter-url = https://www.sydney.edu.au/medicine/pharmacology/adrien-albert/images/pdfs/RefsPDFs/376.pdf | access-date = 2024-05-04 | archive-url = https://web.archive.org/web/20201109012745/https://www.sydney.edu.au/medicine/pharmacology/adrien-albert/images/pdfs/RefsPDFs/376.pdf | archive-date = 9 November 2020 | url-status = dead }}</ref> Of GABA<sub>A</sub>, it may possibly be selective for the subunits predominantly implicated in cognitive and memory functioning such as [[GABRA1|α1]]{{Citation needed|date=December 2014}}.


==See also==
== See also ==
* [[Ginkgolide]]
* [[Ginkgolide]]


==References==
== References ==
{{Reflist|2}}
{{Reflist|2}}

== External links ==
*{{Commons category-inline}}


{{GABAergics}}
{{GABAergics}}
Line 63: Line 68:
[[Category:Glycine receptor antagonists]]
[[Category:Glycine receptor antagonists]]
[[Category:Tert-butyl compounds]]
[[Category:Tert-butyl compounds]]
[[Category:Heterocyclic compounds (4 or more rings)]]
[[Category:Heterocyclic compounds with 4 rings]]
[[Category:Nootropics]]
[[Category:Lactones]]

Latest revision as of 02:29, 26 June 2024

Bilobalide
Clinical data
Routes of
administration		By mouth
Legal status
Legal status
  • In general: legal
Identifiers
  • (5aR-(3aS*,5aα,8b,8aS*,9a,10aα))-9-(1,1-dimethylethyl)-10,10a-dihydro-8,9-dihydroxy-4H,5aH,9H-furo[2,3-b]furo[3',2':2,3]cyclopenta[1,2-c]furan-2,4,7(3H,8H)-trione
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.125.716 Edit this at Wikidata
Chemical and physical data
FormulaC15H18O8
Molar mass326.301 g·mol−1
3D model (JSmol)
  • CC(C)(C)[C@@]1(C[C@H]2[C@@]3([C@]14[C@H](C(=O)O[C@H]4OC3=O)O)CC(=O)O2)O
  • InChI=1S/C15H18O8/c1-12(2,3)14(20)4-6-13(5-7(16)21-6)10(19)23-11-15(13,14)8(17)9(18)22-11/h6,8,11,17,20H,4-5H2,1-3H3/t6-,8-,11-,13-,14+,15?/m0/s1 checkY
  • Key:MOLPUWBMSBJXER-ISSLQHLCSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Bilobalide is a biologically active terpenic trilactone present in Ginkgo biloba.[1]

Chemistry

[edit]

Bilobalide is a main constituent of the terpenoids found in Ginkgo leaves. It also exists in minor amounts in the roots. It is a sesquiterpenoid, i.e. it has a 15-carbon skeleton. Its exact synthesis pathway from farnesyl pyrophosphate is still unknown.

Biosynthesis

[edit]

Bilobalide and ginkgolide have similar biosynthetic pathways. Bilobalide is formed by partially degraded ginkgolide. Bilobalide is derived from geranylgeranyl pyrophosphate (GGPP), which is formed by addition of farnesyl pyrophosphate (FPP) to an isopentenyl pyrophosphate (IPP) unit to form a C15 sesquiterpene. Such formation went through the mevalonate pathway (MVA) and methylerythritol phosphate MEP pathway. In order to generate bilobalide, C20 ginkgolide 13 must form first. To transform from GGPP to abietenyl cation 5, a single bifunctional enzyme abietadiene synthase E1 is required. However, due to the complexity of ginkgolide structures for rearrangement, ring cleavage, and formation of lactone rings, diterpene 8 is used to explain instead. Levopimaradiene 6 and abietatriene 7 are precursors for ginkgolide and bilobalide formation. The unusual tert-butyl substituent is formed from A ring cleavage in 9. Bilobalide 13 then formed in loss of carbons through degradation from ginkgolide 12, and lactones are formed from residual carboxyl and alcohol functions. The end product of bilobalide contains sesquiterpenes and three lactones units.[2]

Biosynthesis mechanism of Bilobalide.

Pharmacology

[edit]

Bilobalide is important for producing several of the effects of Ginkgo biloba extracts, and it has neuroprotective effects,[3][4] as well as inducing the liver enzymes CYP3A1 and CYP1A2,[5] which may be partially responsible for interactions between ginkgo and other herbal medicines or pharmaceutical drugs. Bilobalide has recently been found to be a negative allosteric modulator at the GABAA and GABAA-rho receptors.[6] Of GABAA, it may possibly be selective for the subunits predominantly implicated in cognitive and memory functioning such as α1[citation needed].

See also

[edit]

References

[edit]
  1. ^ van Beek TA, Montoro P (March 2009). "Chemical analysis and quality control of Ginkgo biloba leaves, extracts, and phytopharmaceuticals". Journal of Chromatography A. 1216 (11): 2002–2032. doi:10.1016/j.chroma.2009.01.013. PMID 19195661.
  2. ^ Dewick PM (2009). Medicinal Natural Products: Products: A Biosynthetic Approach (Third ed.). West Sussex, England: Wiley&Sons. pp. 230–232. ISBN 978-0-470-74168-9.
  3. ^ Defeudis FV (December 2002). "Bilobalide and neuroprotection". Pharmacological Research. 46 (6): 565–568. doi:10.1016/S1043-6618(02)00233-5. PMID 12457632.
  4. ^ Kiewert C, Kumar V, Hildmann O, Hartmann J, Hillert M, Klein J (March 2008). "Role of glycine receptors and glycine release for the neuroprotective activity of bilobalide". Brain Research. 1201: 143–150. doi:10.1016/j.brainres.2008.01.052. PMID 18325484. S2CID 5191088.
  5. ^ Deng Y, Bi HC, Zhao LZ, He F, Liu YQ, Yu JJ, et al. (May 2008). "Induction of cytochrome P450s by terpene trilactones and flavonoids of the Ginkgo biloba extract EGb 761 in rats". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 38 (5): 465–481. doi:10.1080/00498250701883233. PMID 18421621. S2CID 84019088.
  6. ^ Johnston GA, Hanrahan JR, Chebib M, Duke RK, Mewett KN (2006). "Modulation of ionotropic GABA receptors by natural products of plant origin" (PDF). GABA. Advances in Pharmacology. Vol. 54. Elsevier. pp. 285–316. doi:10.1016/s1054-3589(06)54012-8. ISBN 978-0-12-032957-1. PMID 17175819. Archived from the original (PDF) on 9 November 2020. Retrieved 2024-05-04.
[edit]
Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=Bilobalide&oldid=1231033913"