Chemical Composition and Toxicity Studies on L. Flower Essential Oil and Its Binding and Pharmacokinetics to Superoxide Dismutase 1 for Amyotrophic Lateral Sclerosis (ALS) Therapy

Overview

Journal RSC Adv

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2024 Aug 6

PMID 39104562

Authors

Abdullah Haikal

Ahmed R Ali

Affiliations

Soon will be listed here.

Abstract

Using the gas chromatography mass spectrometry method, the chemical components of essential oil from flowers of growing in Egypt are analyzed. Through this investigation, 22 chemicals from floral oil were identified. Most of the oil is made up of sesquiterpene caryophyllene (15.51%) and monoterpene sabinene (14.90%). When the oil's composition was compared to oils extracted from the same plant on several continents, we observed that the essential components were largely the same with some difference in proportions and some compounds due to geographical differences. A molecular docking study of essential oil components was conducted with human superoxide dismutase 1, a target involved in the pathophysiology of amyotrophic lateral sclerosis (ALS). Isospathulenol showed a comparable docking score to the reference ligand bound to the dismutase enzyme. Isospathulenol showed a reasonable drug score with some safety concerns. In addition, isospathulenol is predicted to have high GI absorption, good permeability through the blood-brain barrier and reasonable bioavailability score with ease access to synthetic modifications. In addition, the same compound is devoid from any violation to Lipinski rules or any PAINS alerts. This may establish the promising characteristics of such a compound to be optimized into potential drug candidates for treatment of ALS.

References

Rosen D, Siddique T, Patterson D, Figlewicz D, Sapp P, Hentati A . Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993; 362(6415):59-62. DOI: 10.1038/362059a0. View

Pattee G, Genge A, Couratier P, Lunetta C, Sobue G, Aoki M . Oral Edaravone - Introducing a Flexible Treatment Option for Amyotrophic Lateral Sclerosis. Expert Rev Neurother. 2023; 23(10):859-866. DOI: 10.1080/14737175.2023.2251687. View

Herbert J, Maffrand J, Taoubi K, Augereau J, Fouraste I, Gleye J . Verbascoside isolated from Lantana camara, an inhibitor of protein kinase C. J Nat Prod. 1991; 54(6):1595-600. DOI: 10.1021/np50078a016. View

Lipinski C, Lombardo F, Dominy B, Feeney P . Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001; 46(1-3):3-26. DOI: 10.1016/s0169-409x(00)00129-0. View

Haikal A, Galala A, Elshal M, Amen Y, Gohar A . Bioactivity of Eriocephalus africanus essential oil against concanavalin A-induced hepatitis via suppressing immune cell infiltration, inhibiting TNF-α/NF-κB and IFN-γ/STAT1 signaling pathways. J Ethnopharmacol. 2023; 318(Pt B):117000. DOI: 10.1016/j.jep.2023.117000. View

Zarei S, Carr K, Reiley L, Diaz K, Guerra O, Fernandez Altamirano P . A comprehensive review of amyotrophic lateral sclerosis. Surg Neurol Int. 2015; 6:171. PMC: 4653353. DOI: 10.4103/2152-7806.169561. View

Begum S, Wahab A, Siddiqui B . Antimycobacterial activity of flavonoids from Lantana camara Linn. Nat Prod Res. 2008; 22(6):467-70. DOI: 10.1080/14786410600898714. View

Lee J, Hyeon S, Im H, Ryu H, Kim Y, Ryu H . Astrocytes and Microglia as Non-cell Autonomous Players in the Pathogenesis of ALS. Exp Neurobiol. 2016; 25(5):233-240. PMC: 5081469. DOI: 10.5607/en.2016.25.5.233. View

Sharma O, Singh A, Sharma S . Levels of lantadenes, bioactive pentacyclic triterpenoids, in young and mature leaves of Lantana camara var. aculeata. Fitoterapia. 2001; 71(5):487-91. DOI: 10.1016/s0367-326x(00)00156-8. View

10.

Soares P, Silva C, Chavarria D, Silva F, Oliveira P, Borges F . Drug discovery and amyotrophic lateral sclerosis: Emerging challenges and therapeutic opportunities. Ageing Res Rev. 2022; 83:101790. DOI: 10.1016/j.arr.2022.101790. View

11.

Begum S, Ayub A, Qamar Zehra S, Siddiqui B, Choudhary M, Samreen . Leishmanicidal Triterpenes from Lantana camara. Chem Biodivers. 2014; 11(5):709-18. DOI: 10.1002/cbdv.201300151. View

12.

Arthur K, Calvo A, Price T, Geiger J, Chio A, Traynor B . Projected increase in amyotrophic lateral sclerosis from 2015 to 2040. Nat Commun. 2016; 7:12408. PMC: 4987527. DOI: 10.1038/ncomms12408. View

13.

Gitler A, Dhillon P, Shorter J . Neurodegenerative disease: models, mechanisms, and a new hope. Dis Model Mech. 2017; 10(5):499-502. PMC: 5451177. DOI: 10.1242/dmm.030205. View

14.

Abdel-Hady N, Abdei-Halim A, Al-Ghadban A . Chemical composition and insecticidal activity of the volatile oils of leaves and flowers of Lantana camara L. cultivated in Egypt. J Egypt Soc Parasitol. 2005; 35(2):687-98. View

15.

Tang L, Ma Y, Liu X, Chen L, Fan D . Better survival in female -mutant patients with ALS: a study of -related natural history. Transl Neurodegener. 2019; 8:2. PMC: 6325854. DOI: 10.1186/s40035-018-0142-8. View

16.

Brasil A, de Carvalho M, Gerhardt E, Queiroz D, Pereira M, Outeiro T . Characterization of the activity, aggregation, and toxicity of heterodimers of WT and ALS-associated mutant Sod1. Proc Natl Acad Sci U S A. 2019; 116(51):25991-26000. PMC: 6926019. DOI: 10.1073/pnas.1902483116. View

17.

Sathish R, Vyawahare B, Natarajan K . Antiulcerogenic activity of Lantana camara leaves on gastric and duodenal ulcers in experimental rats. J Ethnopharmacol. 2010; 134(1):195-7. DOI: 10.1016/j.jep.2010.11.049. View

18.

Baell J, Holloway G . New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J Med Chem. 2010; 53(7):2719-40. DOI: 10.1021/jm901137j. View

19.

Tesch N, Mora F, Rojas L, Diaz T, Velasco J, Yanez C . Chemical composition and antibacterial activity of the essential oil of Lantana camara var. moritziana. Nat Prod Commun. 2011; 6(7):1031-4. View

20.

Dua V, Pandey A, Dash A . Adulticidal activity of essential oil of Lantana camara leaves against mosquitoes. Indian J Med Res. 2010; 131:434-9. View