Author(s):
Besse Hardianti, Astuti Amin, Subehan Lallo, Ai Hertati
Email(s):
bessehardianti@univeral.ac.id , amin.astuti@gmail.com , aihe001@brin.go.id , subehan@unhas.ac.id
DOI:
10.52711/0974-360X.2024.00914 
Address:
Besse Hardianti1*, Astuti Amin1, Subehan Lallo2, Ai Hertati3
1Faculty of Science and Health, Almarisah Madani University, Makassar, Makassar 90242, Indonesia.
2Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Indonesia.
3Research Center of Genetic Engineering National Research and Innovation Agency (BRIN) KST Soekarno Cibinong, Jawa Barat 16911, Indonesia.
*Corresponding Author
Published In:
Volume - 17,
Issue - 12,
Year - 2024
ABSTRACT:
Chromolaena odorata L. is an unexploited weed that can be used in various traditional medicine systems. This study aims to identify active compounds that have effects as antioxidants from three parts of C. odorata weed leaves (LOD), stems (SOD), and roots (ROD) in vitro and silico as active ingredient candidates against lung cancer. Antioxidants were carried out using Beta Carotene Bleaching (BCB), Nitric Oxide (NO), and Cupric Ion Reducing Antioxidant Capacity (CUPRAC) methode. Identification of lung anticancer compounds with silicon molecular docking method compares Gefitinib (5GU8) protein binding affects lung cancer cell growth. From the results of identification with GC–MS from ethanol extract of C. odorata, eight metabolites were obtained, most of which were phenolic, and FT–IR profile obtained the presence of C–H, C=C, C–O, N–H, C–N, and O–H groups. In antioxidant testing with BCB, NO and CUPRAC methods showed powerful antioxidant activity in ethanol extract LOD (IC50=50), in ethanol extract SOD with strong activity (IC50 = 50–100), and ethanol extract ROD obtained moderate activity (IC50 = 100–150). The total phenolic content (TPC) of C. odorata extracts varied significantly (P < 0.05) from 2.319–7.518±0.023–0.04 and total flavonoid content (TFC) 0.434±0.022–0.41. Pearson correlation test and principal component analysis showed the relationship between TPC and TFC of various antioxidant activity assays of C. odorata extracts. In–silico studies of eight compounds were found to fulfill Lipinski's Rule of Five, which means they have good bioavailability. The molecular docking simulation results showed that each compound had a better affinity to EGFR than Gefitinib (5GU8). Visualization showed that the compounds interacted with amino acid residues Met793, Gln791, Leu718, Thr854, Asp855, and Lys745. Toxicity testing showed that the compounds obtained were non-toxic and non-carcinogenic. The results indicate that the compounds obtained can be used as anti-lung cancer candidates through EGFR inhibition.
Cite this article:
Besse Hardianti, Astuti Amin, Subehan Lallo, Ai Hertati. Phytochemical composition by GC–MS, Invitro Antioxidant, Insilico chemical active compound of Chromolaena odorata L. weed extract targeting EGFR as Anti Lung Cancer. Research Journal Pharmacy and Technology. 2024;17(12):6020-1. doi: 10.52711/0974-360X.2024.00914
Cite(Electronic):
Besse Hardianti, Astuti Amin, Subehan Lallo, Ai Hertati. Phytochemical composition by GC–MS, Invitro Antioxidant, Insilico chemical active compound of Chromolaena odorata L. weed extract targeting EGFR as Anti Lung Cancer. Research Journal Pharmacy and Technology. 2024;17(12):6020-1. doi: 10.52711/0974-360X.2024.00914 Available on: https://rjptonline.org/AbstractView.aspx?PID=2024-17-12-51
REFERENCES:
1. Poofery J, Khaw-on P, Subhawa S, et al. Potential of Thai Herbal Extracts on Lung Cancer Treatment by Inducing Apoptosis and Synergizing Chemotherapy. Molecules. 2020; 25(1): 231. doi:10.3390/molecules25010231
2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6): 394-424. doi:10.3322/caac.21492
3. Hanif A, Ibrahim AH, Ismail S, et al. Cytotoxicity against A549 Human Lung Cancer Cell Line via the Mitochondrial Membrane Potential and Nuclear Condensation Effects of Nepeta paulsenii Briq., a Perennial Herb. Molecules. 2023; 28(6): 2812. doi:10.3390/molecules28062812
4. Amin A, Khairi N, Hendrarti W. Aktivitas Antioksidan Ekstrak Etanol Batang, Daun, dan Akar Kopasanda (Chromolaena odorata L.) dengan Metode FRAP (Ferric Reducing Antioxidant Power): Antioxidant Activity of Ethanol Extract of Stems, Leaves, and Roots of Kopasanda (Chromolaena odorata L.) with FRAP (Ferric Reducing Antioxidant Power) Method. Jurnal Sains dan Kesehatan. 2022; 4(5): 473-480. doi:10.25026/jsk.v4i5.1271
5. Omokhua-Uyi AG, Madikizela B, Aro AO, Abdalla MA, Van Staden J, McGaw LJ. Flavonoids of Chromolaena odorata (L.) R.M.King and H.Rob. as potential leads for treatment against tuberculosis. South African Journal of Botany. 2023; 158: 158-165. doi:10.1016/j.sajb.2023.05.002
6. Omokhua AG, McGaw LJ, Finnie JF, Van Staden J. Chromolaena odorata (L.) R.M. King and H. Rob. (Asteraceae) in sub-Saharan Africa: A synthesis and review of its medicinal potential. Journal of Ethnopharmacology. 2016; 183: 112-122. doi:10.1016/j.jep.2015.04.057
7. Amin A, Tengker SMT, Hendrarti W. Aktivitas Antioksidan Ekstrak Etanol Batang, Daun Dan Akar Kopasanda (Chromolaena odorata L) dengan Metode ABTS (2,2’- azino - bis (3-etilbenzotiazolin -6- asam sulfonat). Published online 2022.
8. Budha Magar A, Shrestha D, Pakka S, Sharma KR. Phytochemistry, Biological, and Toxicity Study on Aqueous and Methanol Extracts of Chromolaena odorata. Dalal V, ed. The Scientific World Journal. 2023;2023:1-11. doi:10.1155/2023/6689271
9. Boudjeko T, Megnekou R, Woguia AL, et al. Antioxidant and immunomodulatory properties of polysaccharides from Allanblackia floribunda Oliv stem bark and Chromolaena odorata (L.) King and H.E. Robins leaves. BMC Research Notes. 2015;8(1):759. doi:10.1186/s13104-015-1703-x
10. Putri DA, Fatmawati S. A New Flavanone as a Potent Antioxidant Isolated from Chromolaena odorata L. Leaves. Evidence-Based Complementary and Alternative Medicine. 2019;2019:1-12. doi:10.1155/2019/1453612
11. Oliveira J, Bernardi D, Balbinot R, et al. Chemotaxonomic value of flavonoids in Chromolaena congesta (Asteraceae). Biochemical Systematics and Ecology. 2017;70:7-13. doi:10.1016/j.bse.2016.10.013
12. Sirinthipaporn A, Jiraungkoorskul W. Wound healing property review of siam weed, Chromolaena odorata. Phcog Rev. 2017;11(21):35. doi:10.4103/phrev.phrev_53_16
13. Ghasemzadeh A, Jaafar HZE, Rahmat A, Ashkani S. Secondary metabolites constituents and antioxidant, anticancer and antibacterial activities of Etlingera elatior (Jack) R.M.Sm grown in different locations of Malaysia. BMC Complement Altern Med. 2015;15:335. doi:10.1186/s12906-015-0838-6
14. P. E, S. S, Anbiah SV. Phytochemical analysis of ethanolic extract of leaves of Caesalpinia bonducella. RJPT. Published online November 30, 2021:5891-5894. doi:10.52711/0974-360X.2021.01024
15. K. Kar S, Nayak S, S. Mishra U, K. Dixit P, R. Pradhan S, Pradhan S. Phytochemical Analysis and Antioxidant activity of Byttneria herbacea (Malvaceae). RJPT. Published online April 29, 2023:1659-1663. doi:10.52711/0974-360X.2023.00271
16. RATHER G, Nanda A, Raj E, et al. Determination of Phytochemicals, in vitro Antioxidant and Antibacterial activity of Lavandula angustifolia Mill. Research Journal of Pharmacy and Technology. Published online March 31, 2023:1161-1166. doi:10.52711/0974-360X.2023.00193
17. Sankhalkar S, Vernekar V, Vernekar V, Vernekar V. Quantitative and Qualitative analysis of Phenolic and Flavonoid content in Moringa oleifera Lam and Ocimum tenuiflorum L. Pharmacognosy Research. 2016; 8(1): 16-21. doi:10.4103/0974-8490.171095
18. Abd-Almonuim AE, Mohammed SM, Al-Khalifa II. Preparation, Characterization and Antioxidant Determination of Coumarin Substituted Heterocyclic Compound. Asia Jour Rese Chem. 2020; 13(1): 23. doi:10.5958/0974-4150.2020.00006.1
19. Jana K, Ghosh A, Debnath B, Das S. GC-MS Analysis of Phytocomponents of Methanolic Bark Extract of Sterculia Foetida.; 2023. doi:10.52711/0974-360X.2023.00909
20. Nurcholis W, Sya’bani Putri DN, Husnawati H, Aisyah SI, Priosoeryanto BP. Total flavonoid content and antioxidant activity of ethanol and ethyl acetate extracts from accessions of Amomum compactum fruits. Annals of Agricultural Sciences. 2021; 66(1): 58-62. doi:10.1016/j.aoas.2021.04.001
21. Baeshen NA, Almulaiky YQ, Afifi M, et al. GC-MS Analysis of Bioactive Compounds Extracted from Plant Rhazya stricta Using Various Solvents. Plants. 2023; 12(4): 960. doi:10.3390/plants12040960
22. Chandra Murthy CSSR, Kumar Sanapala A, Sambamoorthy U, Paul Babu K, Sunkara N. Phytochemical screening and Invitro Anticancer activity of Lonicera ligustrina leaf extract on Breast and Colorectal carcinoma cell lines. RJPT. Published online August 30, 2022: 3485-3489. doi:10.52711/0974-360X.2022.00584
23. Bajes H, Oran S, Bustanji Y. Phytochemical Analysis, In vitro Assessment of Antioxidant Properties and Cytotoxic Potential of Thymus capitatus Essential Oil. Research Journal of Pharmacy and Technology. Published online March 31, 2023:1100-1108. doi:10.52711/0974-360X.2023.00183
24. K. Patel S, K Shutter A, Patil R, et al. In-Vitro Antioxidant, Anti-Inflammatory and Cytotoxic effects of different Solvent Extraction Terminalia chebula, Terminalia billerica, Phyllanthus emblica. RJPT. Published online July 29, 2022:2940-2944. doi:10.52711/0974-360X.2022.00490
25. George J, Edwards D, Pun S, Williams D. Evaluation of Antioxidant Capacity (ABTS and CUPRAC) and Total Phenolic Content (Folin-Ciocalteu) Assays of Selected Fruit, Vegetables, and Spices. Int J Food Sci. 2022; 2022: 2581470. doi:10.1155/2022/2581470
26. Ervina M, Pratama MRF, Poerwono H, et al. In silico estrogen receptor alpha antagonist studies and toxicity prediction of Melia azedarach leaves bioactive ethyl acetate fraction. J Adv Pharm Technol Res. 2021; 12(3): 236-241. doi:10.4103/japtr.JAPTR_198_21
27. Kumar S, Ali I, Abbas F, et al. In-silico identification of small molecule benzofuran-1,2,3-triazole hybrids as potential inhibitors targeting EGFR in lung cancer via ligand-based pharmacophore modeling and molecular docking studies. In Silico Pharmacol. 2023; 11(1): 20. doi:10.1007/s40203-023-00157-1
28. Hussein EA, Thron C, Ghaziasgar M, Vaccari M, Marnewick JL, Hussein AA. Comparison of Phenolic Content and Antioxidant Activity for Fermented and Unfermented Rooibos Samples Extracted with Water and Methanol. Plants. 2022; 11(1): 16. doi:10.3390/plants11010016
29. Bacsik Z, Mink J, Keresztury G. FTIR Spectroscopy of the Atmosphere. I. Principles and Methods. Applied Spectroscopy Reviews. 2004; 39(3): 295-363. doi:10.1081/ASR-200030192
30. Toscano G, Maceratesi V, Leoni E, Stipa P, Laudadio E, Sabbatini S. FTIR spectroscopy for determination of the raw materials used in wood pellet production. Fuel. 2022; 313: 123017. doi:10.1016/j.fuel.2021.123017
31. A. A, Pavithra RC, S. K. An In vitro Analysis of Ficus carica’s Antioxidant Potential. RJPT. Published online February 28, 2023: 676-680. doi:10.52711/0974-360X.2023.00115
32. T.K. B, Udayan PS. GC-MS analysis of bioactive compounds in methanolic extract of tubers of Pueraria tuberosa (Roxb. ex Willd.) DC. - Fabaceae. IJEAB. 2018; 3(4): 1493-1498. doi:10.22161/ijeab/3.4.47
33. Fofana S, Delporte C, Calvo Esposito R, et al. In Vitro Antioxidant and Anticancer Properties of Various E. senegalensis Extracts. Molecules. 2022; 27(8): 2583. doi:10.3390/molecules27082583
34. Petricevich VL, Cedillo-Cortezano M, Abarca-Vargas R. Chemical Composition, Antioxidant Activity, Cytoprotective and In Silico Study of Ethanolic Extracts of Bougainvillea × buttiana (Var. Orange and Rose). Molecules. 2022; 27(19): 6555. doi:10.3390/molecules27196555
35. Trofin AE, Trincă LC, Ungureanu E, Ariton AM. CUPRAC Voltammetric Determination of Antioxidant Capacity in Tea Samples by Using Screen-Printed Microelectrodes. Journal of Analytical Methods in Chemistry. 2019; 2019: e8012758. doi:10.1155/2019/8012758
36. Apak R, Güçlü K, Özyürek M, Bektas¸oğlu B, Bener M. Cupric Ion Reducing Antioxidant Capacity Assay for Food Antioxidants: Vitamins, Polyphenolics, and Flavonoids in Food Extracts. In: Armstrong D, ed. Advanced Protocols in Oxidative Stress I. Methods In Molecular Biology. Humana Press; 2008: 163-193. doi:10.1007/978-1-60327-517-0_14
37. Phuyal N, Jha PK, Raturi PP, Rajbhandary S. Total Phenolic, Flavonoid Contents, and Antioxidant Activities of Fruit, Seed, and Bark Extracts of Zanthoxylum armatum DC. The Scientific World Journal. 2020; 2020: e8780704. doi:10.1155/2020/8780704
38. Hidayat S, Ibrahim FM, Suhandi C, Muchtaridi M. A systematic review: Molecular docking simulation of small molecules as anticancer non-small cell lung carcinoma drug candidates. J Adv Pharm Technol Res. 2022; 13(3): 141-147. doi:10.4103/japtr.japtr_311_21
39. Harfiani E, Nugraha Y, Aprilia C, et al. The phytochemical and pharmacological activity of extract Kirinyuh (Chromolaena odorata L.) leaves: A Review. Pharmacognosy Journal. 2022; 14: 580-586. doi:10.5530/pj.2022.14.139
40. Eze FN, Jayeoye TJ. Chromolaena odorata (Siam weed): A natural reservoir of bioactive compounds with potent anti-fibrillogenic, antioxidative, and cytocompatible properties. Biomedicine and Pharmacotherapy. 2021; 141: 111811. doi:10.1016/j.biopha.2021.111811
41. Truong DH, Nguyen DH, Ta NTA, Bui AV, Do TH, Nguyen HC. Evaluation of the Use of Different Solvents for Phytochemical Constituents, Antioxidants, and In Vitro Anti-Inflammatory Activities of Severinia buxifolia. Journal of Food Quality. 2019;2019:e8178294. doi:10.1155/2019/8178294
42. Bolade OP, Akinsiku AA, Adeyemi AO, Williams AB, Benson NU. Dataset on phytochemical screening, FTIR and GC–MS characterisation of Azadirachta indica and Cymbopogon citratus as reducing and stabilising agents for nanoparticles synthesis. Data in Brief. 2018; 20: 917-926. doi:10.1016/j.dib.2018.08.133
43. Ayouaz S, Koss-Mikołajczyk I, Abdellatif NA, et al. Anticarcinogenic and antioxidant activities of leaves and flowers hydroalcoholic extracts of Nerium oleander L.: PCA analysis and phytochemical content by FTIR spectroscopy. Nor Afr J Food Nutr Res. 2023; 7(15): 1-8. doi:10.51745/najfnr.7.15.1-8
44. Jozanikohan G, Abarghooei MN. The Fourier transform infrared spectroscopy (FTIR) analysis for the clay mineralogy studies in a clastic reservoir. J Petrol Explor Prod Technol. 2022; 12(8): 2093-2106. doi:10.1007/s13202-021-01449-y
45. Chalkha M, Chebbac K, Nour H, et al. In vitro and in silico evaluation of the antimicrobial and antioxidant activities of spiropyrazoline oxindole congeners. Arabian Journal of Chemistry. 2024; 17(1): 105465. doi:10.1016/j.arabjc.2023.105465
46. Hikmawanti NPE, Saputri FC, Yanuar A, et al. Choline chloride-urea-based natural deep eutectic solvent for highly efficient extraction of polyphenolic antioxidants from Pluchea indica (L.) Less leaves. Arabian Journal of Chemistry. 2024; 17(2): 105537. doi:10.1016/j.arabjc.2023.105537
47. Dahham SS, Al-Rawi SS, Ibrahim AH, Abdul Majid AS, Abdul Majid AMS. Antioxidant, anticancer, apoptosis properties and chemical composition of black truffle Terfezia claveryi. Saudi Journal of Biological Sciences. 2018; 25(8): 1524-1534. doi:10.1016/j.sjbs.2016.01.031
48. Mazumder K, Nabila A, Aktar A, Farahnaky A. Bioactive Variability and In Vitro and In Vivo Antioxidant Activity of Unprocessed and Processed Flour of Nine Cultivars of Australian lupin Species: A Comprehensive Substantiation. Antioxidants (Basel). 2020; 9(4): 282. doi:10.3390/antiox9040282
49. Chen Z, Zhong B, Barrow CJ, Dunshea FR, Suleria HAR. Identification of phenolic compounds in Australian grown dragon fruits by LC-ESI-QTOF-MS/MS and determination of their antioxidant potential. Arabian Journal of Chemistry. 2021;14(6):103151. doi:10.1016/j.arabjc.2021.103151
50. Al-Momani LA, Abu-Orabi ST, Hlail HM, Alkhatib RQ, Al-Dalahmeh Y, Al-Qudah MA. Anthemis cotula L. from Jordan: Essential oil composition, LC-ESI-MS/MS profiling of phenolic acids - flavonoids and in vitro antioxidant activity. Arabian Journal of Chemistry. 2023; 16(2): 104470. doi:10.1016/j.arabjc.2022.104470
51. Mumtaz MZ, Kausar F, Hassan M, Javaid S, Malik A. Anticancer activities of phenolic compounds from Moringa oleifera leaves: in vitro and in silico mechanistic study. Beni-Suef University Journal of Basic and Applied Sciences. 2021; 10(1): 12. doi:10.1186/s43088-021-00101-2
52. Amrati FEZ, Chebaibi M, Galvão de Azevedo R, et al. Phenolic Composition, Wound Healing, Antinociceptive, and Anticancer Effects of Caralluma europaea Extracts. Molecules. 2023; 28(4): 1780. doi:10.3390/molecules28041780
53. Lekmine S, Benslama O, Kadi K, et al. LC/MS-MS Analysis of Phenolic Compounds in Hyoscyamus albus L. Extract: In Vitro Antidiabetic Activity, In Silico Molecular Docking, and In Vivo Investigation against STZ-Induced Diabetic Mice. Pharmaceuticals. 2023; 16(7): 1015. doi:10.3390/ph16071015
54. Yamaoka T, Ohba M, Ohmori T. Molecular-Targeted Therapies for Epidermal Growth Factor Receptor and Its Resistance Mechanisms. International Journal of Molecular Sciences. 2017; 18(11): 2420. doi:10.3390/ijms18112420