Generic placeholder image

Combinatorial Chemistry & High Throughput Screening


ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Analysis of Pharmacological Activities and Mechanisms of Essential Oil in Leaves of C. grandis ‘Tomentosa’ by GC-MS/MS and Network Pharmacology

Author(s): Jie-Shu You, Sheng-Cai He, Liang Chen, Zhen-Hui Guo, Fei Gao, Min-Yue Zhang, Liu Dan* and Wei Chen*

Volume 26, Issue 9, 2023

Published on: 30 December, 2022

Page: [1689 - 1700] Pages: 12

DOI: 10.2174/1386207325666220610182644

open access plus


Background: Citrus grandis ‘Tomentosa,’ a fruit epicarp of C. grandis ‘Tomentosa’ or C. grandis (L.) Osbeck is widely used in health food and medicine. Based on our survey results, there are also rich essential oils with bioactivities in leaves, but the chemical compounds in this part and relevant pharmacological activities have never been studied systematically. Therefore, this study was to preliminarily decipher the pharmacological activities and mechanisms of the essential oil in leaves of C. grandis ‘Tomentosa’ by an integrated network pharmacology approach.

Methods: Essential oil compositions from leaves ofC. grandis ‘Tomentosa’ were identified using GC-MS/MS. And then, the targets of these oil compositions were predicted and screened from TCMSP, SwissTargetPrediction, STITCH and SEA databases. STRING database was used to construct the protein-protein interaction networks, and the eligible protein targets were input into WebGestalt 2019 to carry out GO enrichment and KEGG pathway enrichment analysis. Based on the potential targets, disease enrichment information was obtained by TTD databases. Cytoscape software was used to construct the component-target-disease network diagrams.

Results: Finally, 61 essential oil chemical components were identified by GC-MS/MS, which correspond to 679 potential targets. Biological function analysis showed 12, 19, and 12 GO entries related to biological processes, cell components and molecular functions, respectively. 43 KEGG pathways were identified, of which the most significant categories were terpenoid backbone biosynthesis, TNF signaling pathway and leishmaniasis. The component-target-disease network diagram revealed that the essential oil compositions in leaves of C. grandis ‘Tomentosa’ could treat tumors, immune diseases, neurodegenerative diseases and respiratory diseases, which were highly related to CHRM1, PTGS2, CASP3, MAP2K1 and CDC25B.

Conclusion: This study may provide new insight into C. grandis ‘Tomentosa’ or C. grandis (L.) Osbeck and may provide useful information for future utilization and development.

Keywords: Leaves of C. grandis ‘Tomentosa, ’ essential oils, GC-MS/MS, network pharmacology, component-target-disease, tomentosa.

Graphical Abstract
Chen, Z.; Lin, L. Study on coumarin compounds from Exocarpium Citri grandis. Zhong Yao Cai, 2004, 27(8), 577-578.
[PMID: 15658818]
Nogata, Y.; Sakamoto, K.; Shiratsuchi, H.; Ishii, T.; Yano, M.; Ohta, H. Flavonoid composition of fruit tissues of citrus species. Biosci. Biotechnol. Biochem., 2006, 70(1), 178-192.
[] [PMID: 16428836]
Li, P.L.; Liu, M.H.; Hu, J.H.; Su, W.W. Systematic chemical profiling of Citrus grandis ‘Tomentosa’ by ultra-fast liquid chromatography/diode-array detector/quadrupole time-of-flight tandem mass spectrometry. J. Pharmaceut. Biomed., 2014, 90, 167-179.
[] [PMID: 24370611]
Yu, J.; Wang, L.; Walzem, R.L.; Miller, E.G.; Pike, L.M.; Patil, B.S. Antioxidant activity of citrus limonoids, flavonoids, and coumarins. J. Agric. Food Chem., 2005, 53(6), 2009-2014.
[] [PMID: 15769128]
Duan, L.; Guo, L.; Dou, L.L.; Yu, K.Y.; Liu, E.H.; Li, P. Comparison of chemical profiling and antioxidant activities of fruits, leaves, branches, and flowers of Citrus grandis ‘Tomentosa’. J. Agric. Food Chem., 2014, 62(46), 11122-11129.
[] [PMID: 25335649]
Lee, M.S.; Choi, J.; Posadzki, P.; Ernst, E. Aromatherapy for health care: An overview of systematic reviews. Maturitas, 2012, 71(3), 257-260.
[] [PMID: 22285469]
Paradis, D.; Bérail, G.; Bonmatin, J.M.; Belzunces, L.P. Sensitive analytical methods for 22 relevant insecticides of 3 chemical families in honey by GC-MS/MS and LC-MS/MS. Anal. Bioanal. Chem., 2014, 406(2), 621-633.
[] [PMID: 24253411]
Hopkins, A.L. Network pharmacology: The next paradigm in drug discovery. Nat. Chem. Biol., 2008, 4(11), 682-690.
[] [PMID: 18936753]
Zhang, R.; Zhu, X.; Bai, H.; Ning, K. Network pharmacology databases for traditional Chinese medicine: Review and assessment. Front. Pharmacol., 2019, 10, 123.
[] [PMID: 30846939]
Li, S.; Fan, T.P.; Jia, W.; Lu, A.; Zhang, W. Network pharmacology in traditional Chinese medicine. Evid. Based Complement. Alternat. Med., 2014, 2014, 138460.
[PMID: 24707305]
Li, S.; Zhang, B. Traditional Chinese medicine network pharmacology: Theory, methodology and application. Chin. J. Nat. Med., 2013, 11(2), 110-120.
[] [PMID: 23787177]
Keiser, M.J.; Roth, B.L.; Armbruster, B.N.; Ernsberger, P.; Irwin, J.J.; Shoichet, B.K. Relating protein pharmacology by ligand chemistry. Nat. Biotechnol., 2007, 25(2), 197-206.
[] [PMID: 17287757]
Smoot, M.E.; Ono, K.; Ruscheinski, J.; Wang, P.L.; Ideker, T. Cytoscape 2.8: New features for data integration and network visualization. Bioinformatics, 2011, 27(3), 431-432.
[] [PMID: 21149340]
Scardoni, G.; Tosadori, G.; Faizan, M.; Spoto, F.; Fabbri, F.; Laudanna, C. Biological network analysis with CentiScaPe: Centralities and experimental dataset integration. F1000 Res., 2014, 3, 139.
[] [PMID: 26594322]
Nawrocki, M.J.; Perek, B.; Sujka-Kordowska, P.; Konwerska, A.; KaKałużna, S.; Zawierucha, P.; Bruska, M.; Zabel, M.; Jemielity, M.; Nowicki, M.; Kempisty, B.; Malińska, A. Differences in expression of genes involved in bone development and morphogenesis in the walls of internal thoracic artery and saphenous vein conduits may provide markers useful for evaluation graft patency. Int. J. Mol. Sci., 2019, 20(19), 19.
[] [PMID: 31581653]
Barabási, A.L.; Oltvai, Z.N. Network biology: Understanding the cell’s functional organization. Nat. Rev. Genet., 2004, 5(2), 101-113.
[] [PMID: 14735121]
Liao, Y.; Wang, J.; Jaehnig, E.J.; Shi, Z.; Zhang, B. WebGestalt 2019: Gene set analysis toolkit with revamped UIs and APIs. Nucleic Acids Res., 2019, 47(W1), W199-W205.
[] [PMID: 31114916]
Wang, Y.; Zhang, S.; Li, F.; Zhou, Y.; Zhang, Y.; Wang, Z.; Zhang, R.; Zhu, J.; Ren, Y.; Tan, Y.; Qin, C.; Li, Y.; Li, X.; Chen, Y.; Zhu, F. Therapeutic target database 2020: Enriched resource for facilitating research and early development of targeted therapeutics. Nucleic Acids Res., 2020, 48(D1), D1031-D1041.
[PMID: 31691823]
Xie, Z.; Liu, Q.; Liang, Z.; Zhao, M.; Yu, X.; Yang, D.; Xu, X. The GC/MS analysis of volatile components extracted by different methods from Exocarpium Citri grandis. J. Anal. Methods Chem., 2013, 2013, 918406.
[] [PMID: 24349825]
Fan, R.Y.; Zhu, C.Y.; Qiu, D.Y.; Zeng, J.W. Comparison of the bioactive chemical components and antioxidant activities in three tissues of six varieties of Citrus grandis ‘Tomentosa’ fruits. Int. J. Food Prop., 2019, 22(1), 1848-1862.
Anmol, R.J.; Marium, S.; Hiew, F.T.; Han, W.C.; Kwan, L.K.; Wong, A.K.Y.; Khan, F.; Sarker, M.M.R.; Chan, S.Y.; Kifli, N.; Ming, L.C. Phytochemical and therapeutic potential of Citrus grandis (L.) Osbeck: A review. J. Evid. Based Integr. Med., 2021, 26X211043741,
[] [PMID: 34657477]
Ou, M.C.; Liu, Y.H.; Sun, Y.W.; Chan, C.F. The Composition, antioxidant and antibacterial activities of cold-pressed and distilled essential oils of Citrus paradisi and Citrus grandis (L.) Osbeck. Evid-based Compl. Alt., 2015, (1), 1-9.
Gan, Q.X.; Wang, J.; Hu, J.; Lou, G.H.; Xiong, H.J.; Peng, C.Y.; Huang, Q.W. Modulation of apoptosis by plant polysaccharides for exerting anti-cancer effects: A review. Front. Pharmacol., 2020, 11, 792.
[] [PMID: 32536869]
Perl, A. Pathogenesis and spectrum of autoimmunity. Methods Mol. Biol., 2012, 900, 1-9.
[] [PMID: 22933062]
Cohen, P.L.; Eisenberg, R.A. The lpr and gld genes in systemic autoimmunity: Life and death in the Fas lane. Immunol. Today, 1992, 13(11), 427-428.
[] [PMID: 1282318]
Jiang, H.; Jayadev, S.; Lardelli, M.; Newman, M. A review of the familial Alzheimer’s disease locus PRESENILIN 2 and its relationship to PRESENILIN 1. J. Alzheimers Dis., 2018, 66(4), 1323-1339.
[] [PMID: 30412492]
Zhou, Y.; Zhang, W.; Easton, R.; Ray, J.W.; Lampe, P.; Jiang, Z.; Brunkan, A.L.; Goate, A.; Johnson, E.M.; Wu, J.Y. Presenilin-1 protects against neuronal apoptosis caused by its interacting protein PAG. Neurobiol. Dis., 2002, 9(2), 126-138.
[] [PMID: 11895366]
Pierce, J.D.; Pierce, J.; Stremming, S.; Fakhari, M.; Clancy, R.L. The role of apoptosis in respiratory diseases. Clin. Nurse Spec., 2007, 21(1), 22-28.
[] [PMID: 17213736]
Griendling, K.K.; Minieri, C.A.; Ollerenshaw, J.D.; Alexander, R.W. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ. Res., 1994, 74(6), 1141-1148.
[] [PMID: 8187280]
Pala, S.; Atilgan, R.; Kuloglu, T.; Yalçın, E.; Kaya, N.; Etem, E. The decrease in hippocampal transient receptor potential M2 (TRPM2) channel and muscarinic acetylcholine receptor 1 (CHRM1) is associated with memory loss in a surgical menopause rat model. Arch. Med. Sci., 2019, 17(1), 228-235.
[] [PMID: 33488875]
Morrow, J.D.; Cho, M.H.; Hersh, C.P.; Pinto-Plata, V.; Celli, B.; Marchetti, N.; Criner, G.; Bueno, R.; Washko, G.; Glass, K.; Choi, A.M.K.; Quackenbush, J.; Silverman, E.K.; DeMeo, D.L. DNA methylation profiling in human lung tissue identifies genes associated with COPD. Epigenetics, 2016, 11(10), 730-739.
[] [PMID: 27564456]
Maeda, Y.; Hizawa, N.; Jinushi, E.; Honda, A.; Takahashi, D.; Fukui, Y.; Konno, S.; Shimizu, T.; Shimizu, H.; Yamaguchi, E.; Nishimura, M. Polymorphisms in the muscarinic receptor 1 gene confer susceptibility to asthma in Japanese subjects. Am. J. Respir. Crit. Care Med., 2006, 174(10), 1119-1124.
[] [PMID: 16931638]
Lou, X.Y.; Ma, J.Z.; Payne, T.J.; Beuten, J.; Crew, K.M.; Li, M.D. Gene-based analysis suggests association of the nicotinic acetylcholine receptor beta1 subunit (CHRNB1) and M1 muscarinic acetylcholine receptor (CHRM1) with vulnerability for nicotine dependence. Hum. Genet., 2006, 120(3), 381-389.
[] [PMID: 16874522]
Khan, R.; Sultana, S. Farnesol attenuates 1,2-dimethylhydrazine induced oxidative stress, inflammation and apoptotic responses in the colon of Wistar rats. Chem. Biol. Interact., 2011, 192(3), 193-200.
[] [PMID: 21453689]
de Araújo Delmondes, G.; Bezerra, D.S.; de Queiroz Dias, D.; de Souza Borges, A.; Araújo, I.M.; Lins da Cunha, G.; Bandeira, P.F.R.; Barbosa, R.; Melo Coutinho, H.D.; Felipe, C.F.B.; Barbosa-Filho, J.M.; Alencar de Menezes, I.R.; Kerntopf, M.R. Toxicological and pharmacologic effects of farnesol (C15H26O): A descriptive systematic review. Food Chem. Toxicol., 2019, 129, 169-200.
[] [PMID: 31029722]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy