Ginkgo Biloba Flavonoid Extracts as a Carbonic Anhydrase II Inhibitors for Acute Mountain Sickness Prevention: A Molecular Docking Study

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Kasidit Wiboonkiat
Chotiphat Pornthanamongkol
Setthawut Intarapradit
Chinnavuth Vatanashevanopakorn
Yodying Dangprapai



Based on research regarding phytomedicine as a prophylactic agent for acute mountain sickness (AMS), Ginkgo biloba extracts are among promising candidates. However, a mechanism of action of these extracts remains unknown. Previous studies have shown that some flavonoids, a phenolic metabolite found in various plants, have capability to inhibit carbonic anhydrase II (CAII), a zinc metalloenzyme that regulates acid-base homeostasis. This inhibition could potentially ameliorate an increase in systolic pressure and respiratory alkalosis found in AMS.


We aim to investigate effectiveness of flavonoid extracts from G biloba as CAII inhibitor for opening up more possibilities of new AMS drug development based on natural extracts.


Molecular docking technique was applied to screen candidate substances in order to shorten a period of the pre-clinical phase of drug development. Applying AutoDockVina docking and LigPlot+ interaction plotting, the results predict a binding affinity and interaction diagram of the coherence between the selected ligands and the CAII zinc binding site.  


All flavonoid extracts demonstrated higher binding affinity score compared to CAII original substrates: carbon dioxide and bicarbonate. Moreover, quercetin, the highest affinity flavonoid, has zinc interaction and H-bond on the enzyme active site, similar to natural ligands with the greater cohesion stability from higher hydrophobic contact.


From the affinity results, G Biloba flavonoids competitively inhibit CAII and consequently mitigate the AMS. They are, therefore, highly likely to be tested as substitute drugs for acetazolamide, which is currently commercially used, in order to reduce the potential side effects of synthetic drug and increase bioavailability. Since this study is a pre-screening in silico, further studies including molecular dynamic, preclinical and clinical testing are essential for further development of a drug for AMS.  

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How to Cite
Wiboonkiat, K., Pornthanamongkol, C., Intarapradit, S., Vatanashevanopakorn, C. and Dangprapai, Y. (2023) “Ginkgo Biloba Flavonoid Extracts as a Carbonic Anhydrase II Inhibitors for Acute Mountain Sickness Prevention: A Molecular Docking Study ”, Journal of Asian Medical Students’ Association. Kuala Lumpur, Malaysia. Available at: (Accessed: 4February2023).
Scientific Papers (EAMSC 2023 Nepal)


Brondino N, De Silvestri A, Re S, Lanati N, Thiemann P, Verna A, et al.

A systematic review and meta-analysis of ginkgo biloba in neuropsychiatric disorders: From ancient tradition to modern-day medicine. Evidence-Based Complementary and Alternative Medicine. 2013;2013:1–11.

Berg JT. ginkgo biloba extract prevents high altitude pulmonary edema in rats. High Altitude Medicine & Biology. 2004;5(4):429–34.

Moraga FA, Flores A, Serra J, Esnaola C, Barriento C. Ginkgo biloba decreases acute mountain sickness in people ascending to high altitude at Ollagüe (3696m) in northern Chile. Wilderness & Environmental Medicine. 2007;18(4):251–7.

Van Patot MC, Keyes LE, Leadbetter G, Hackett PH. ginkgo biloba for prevention of acute mountain sickness: Does it work? High Altitude Medicine & Biology. 2009;10(1):33–43.

Farzam K, Abdullah M. Acetazolamide - StatPearls - NCBI Bookshelf. Acetazolamide - StatPearls - NCBI Bookshelf 2022. (accessed October 21, 2022).

Aditama R, Mujahidin D, Syah YM, Hertadi R. Docking and molecular dynamics simulation of carbonic anhydrase II inhibitors from phenolic and Flavonoid Group. Procedia Chemistry. 2015;16:357–64.

Ude C, Schubert-Zsilavecz M, Wurglics M. Ginkgo biloba extracts: A review of the pharmacokinetics of the active ingredients. Clinical Pharmacokinetics. 2013;52(9):727–49.

Sjöblom B, Polentarutti M, Djinović-Carugo K. Structural study of X-ray induced activation of carbonic anhydrase. Proceedings of the National Academy of Sciences. 2009;106(26):10609–13.