Author(s):
Anik Listiyana, Risma Aprinda Kristanti, Nadya Dharmayanti, Rizkia Milladina Hidayatulloh, Sakinah Baraja
Email(s):
anik.listiyana@kedokteran.uin-malang.ac.id
DOI:
10.52711/0974-360X.2023.00196 
Address:
Anik Listiyana*, Risma Aprinda Kristanti, Nadya Dharmayanti, Rizkia Milladina Hidayatulloh, Sakinah Baraja
Department of Medical Education, Faculty of Medicine and Health Sciences, Universitas Islam Negeri Maulana Malik Ibrahim Malang, Jalan Gajayana 50, Malang 65144, Indonesia.
*Corresponding Author
Published In:
Volume - 16,
Issue - 3,
Year - 2023
ABSTRACT:
Chrysanthemum cinerariifolium (Trev.) Vis. leaves have potential anticancer activity and are expected to inhibit oral squamous cell carcinoma (OSCC) progression. The present study aimed to determine the effect of ethanol extract of C. cinerariifolium leaves on the number of macrophages, IL-17 levels, and degree of keratinization in the OSCC rat model. Thirty male Sprague Dawley rats (weighing 80-160g, 2-3 months old) were randomly divided into five groups (n=6): (1) negative control (healthy rat, untreated); (2) positive control (OSCC rat); (3-5) dose 1, 2 and 3 (OSCC rat received 50, 100 and 200mg/kg BW of C. cinerariifolium leaves, respectively). The tongues of the rats were prepared for Hematoxylin-Eosin (HE) staining and immunohistochemistry. The number of macrophages was determined under a light microscope with 400x magnification. The level of IL-17 was examined using an ELISA assay. The degree of keratinization was calculated using the ImageJ software. All doses of C. cinerariifolium leaves extract could reduce the number of macrophages in OSCC rats. The levels of IL-17 in OSCC rats were decreased after being treated with 100 and 200mg/kg BW of C. cinerariifolium leaves extract. The high dose of C. cinerariifolium leaves extract (200mg/kg BW) reduced the degree of keratinization in the OSCC rat model. The study revealed that C. cinerariifolium leaves extract could inhibit the progression of OSCC by reducing macrophage, IL-17 and keratinization.
Cite this article:
Anik Listiyana, Risma Aprinda Kristanti, Nadya Dharmayanti, Rizkia Milladina Hidayatulloh, Sakinah Baraja. Chrysanthemum cinerariifolium (Trev.) Vis leaves extract reduces the level of Macrophages, Interleukin-17, and Keratinization in Oral squamous cell carcinoma rat model.Research Journal of Pharmacy and Technology 2023; 16(3):1180-6. doi: 10.52711/0974-360X.2023.00196
Cite(Electronic):
Anik Listiyana, Risma Aprinda Kristanti, Nadya Dharmayanti, Rizkia Milladina Hidayatulloh, Sakinah Baraja. Chrysanthemum cinerariifolium (Trev.) Vis leaves extract reduces the level of Macrophages, Interleukin-17, and Keratinization in Oral squamous cell carcinoma rat model.Research Journal of Pharmacy and Technology 2023; 16(3):1180-6. doi: 10.52711/0974-360X.2023.00196 Available on: https://rjptonline.org/AbstractView.aspx?PID=2023-16-3-32
REFERENCES:
1. WHO. Cancer. World Health Organization. 2018. Available on https://www.who.int/news-room/fact-sheets/detail/cancer.
2. Indonesian Ministry of Health. World Cancer Day. Bureau of Communication and Community Services, Ministry of Health, RI Health Ministry. 2019. Available on https://www.kemkes.go.id/article/view/19020100003/hari-kanker-sedunia-2019.html
3. Sugunadevi G, Suresh K, Manoharan S, Vijayaanand MA, Rajalingam K. Modifying Effects of Mosinone-A on Glycoconjugates Levels in 7, 12-Dimethyl benz(a)anthracene Induced Hamster Buccal Pouch Carcinogenesis. Asian Journal of Research Chemistry. 2010;3(2):459-463.
4. Govindasamy S, Kathiresan S. Inhibitory Effect of Mosinone - A on Immunohistochemical Expression of Inflammatory and Angiogenic markers in 7,12-dimethylbenz (a) Anthracene induced Hamster Buccal Pouch Carcinogenesis. Research Journal of Pharmacy and Technology. 2021; 14(2):833-837. doi: 10.5958/0974-360X.2021.00147.5.
5. Niyas FM, Savitha G. Metabolic Antioxidant Status in Oral Squamous Cell Carcinoma. Research Journal of Pharmacy and Technology. 2018; 11(10): 4362-4364. doi: 10.5958/0974-360X.2018.00798.9.
6. Li CC., Shen Z, Bavarian R, Yang F, Bhattacharya A. Oral Cancer: Genetics and the Role of Precision Medicine. Dental Clinic of North America. 2018;2(1):29–46. doi: 10.1016/j.cden.2017.08.002.
7. Sawitri E. Apoptosis of Colorectal Cancer Cell on Sprague-Dawley Rats Induced with 1,2 Dimethylhidrazine and Phyllanthus niruri Linn Extract. International Journal of Science and Engineering. 2016;10(1):45-50. doi: 10.12777/ijse.10.1.45-50
8. Kresno SB. Cancer Immunology: From Immunosurveillance to Immunoescape. Indonesian Journal of Cancer. 2008;2(1):18-23. doi: 10.33371/ijoc.v2i1.33
9. Padmaharish V. Salivary Biomarkers of Oral Cancer – A Review. Research Journal of Pharmacy and Technology. 2016; 9(7):1007-1012. doi: 10.5958/0974-360X.2016.00190.6
10. Avadhani AV, Parachuru VPB, Milne T, Seymour GJ, Rich AM. Multiple Cells Express Interleukin 17 In Oral Squamous Cell Carcinoma. Journal of Oral Pathology & Medicine. 2017;46(1):39–45. doi: 10.1111/jop.12465.
11. Irani S. Pre-Cancerous Lesions In The Oral And Maxillofacial Region: A Literature Review With Special Focus On Etiopathogenesis. Iranian Journal of Pathology. 2016;11(4):303-322.
12. Farci F, Mahabal GD. Hyperkeratosis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. 2021. Available on https://www.ncbi.nlm.nih.gov/books/NBK562206/.
13. Hafeez N. Creatine phosphokinase levels in Oral cancer Patients. Research Journal of Pharmacy and Technology. 2016; 9(10):1577-1580. doi: 10.5958/0974-360X.2016.00310.3
14. Parkin DM, Bray F, Ferlay J, Pisani P. Global Cancer Statistics. CA: A Cancer Journal for Clinicians. 2002;55(2):74–108. doi: 10.3322/canjclin.55.2.74.
15. Taghavi N, Yazdi I. Prognostic Factors of Survival Rate in Oral Squamous Cell Carcinoma: Clinical, Histologic, Genetic and Molecular Concepts. Archives of Iranian Medicine. 2015;8(5):314-9.
16. Sanmugam K. A Study of Lipid Profile Levels in Oral Cancer. Research Journal of Pharmacy and Technology. 2015; 8(9): 1259-1263. doi: 10.5958/0974-360X.2015.00228.0
17. Nivedha Srinivasan, Gheena. S. Prevalence and Incidence of Types of Oral Malignancy- 5 Year Institutional Study. Research Journal of Pharmacy and Technology. 2015; 8(12): 1615-1618. doi: 10.5958/0974-360X.2015.00289.9.
18. El-Waseif AA, Abobaker RA, Abdel-Monem MO, Attia AA, Hassan MG. The Lactobacillus brevis Prebiotic Pure Exo polysaccharide and its Nano crystalline Characterization, anti-colon cancer and cytotoxicity. Research Journal of Pharmacy and Technology. 2021; 14(11):5998-2. doi: 10.52711/0974-360X.2021.01042.
19. Listiyana A, Lestari NA, Irawati S, Indrawijaya YYA, Annisa R, Bhagawan WS, Mutiah R, Ma'arif B. Anticancer Activities and Metabolite Fingerprinting of Uplc-Qtof-Ms/Ms Method From Chrysanthemum cinerariifolium (Trev). Journal of Islamic Pharmacy. 2019;4(1):19–39. doi: 10.18860/jip.v4i1.7728
20. Boutaghane N, Voutquene-Nazabadioko L, Simon A, Harakat D, Benlabed K, Kabouche Z. A New Triterpenic Diester From The Aerial Parts of Chrysanthemum macrocarpum. Phytochemistry Letters. 2013;6(4):519–25. doi: 10.1016/j.phytol.2013.06.009
21. Irawati S. Anticancer Activity Profiling Against Breast Cancer Cells (T47D) And Toxicity to Normal Cells (Vero) In White Chrysanthemum Plants (Chrysamthemum cinerariifolium (Trev.)). Maulana Malik Ibrahim State Islamic University, Malang. 2018.
22. Choi J, Lee E, Lee H, Kim K, Ahn K, Shim B, Kim N, Song M, Baek N, Kim S. Identification of Campesterol From Chrysanthemum coronarium L. and Its Antiangiogenic Activities. Phytherapy Research. 2007;21(10):954–9. doi: 10.1002/ptr.2189.
23. Markopoulos AK. Current aspects on oral squamous cell carcinoma. The Open Dentistry Journal. 2012;6:126-130. doi: 10.2174/1874210601206010126
24. Brzak BL, Mravak-Stipetić M, Canjuga I, Baricević M., Balicević D, Sikora M. and Filipović-Zore I. The frequency and malignant transformation rate of oral lichen planus and leukoplakia--a retrospective study. Coll Antropol. 2012;36(3):773-7.
25. Mohammed F, Fairozekhan AT. Oral Leukoplakia. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. 2021. Available on https://www.ncbi.nlm.nih.gov/books/NBK442013/.
26. Lee JJ, Hung HC, Cheng SJ, Chen YJ, Chiang CP, Liu BY, Jeng JH, Chang HH, Kuo YS, Lan WH, Kok SH. Carcinoma and dysplasia in oral leukoplakias in Taiwan: prevalence and risk factors. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. 2006;101(4):472–480. doi: 10.1016/j.tripleo.2005.07.024.
27. Li N, Sun Z, Han C, Chen J. The Chemopreventive Effects of Tea On Human Oral Precancerous Mucosa Lesions. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.). 1999;220(4):218–24. doi: 10.1046/j.1525-1373.1999.d01-37.x.
28. Tsao AS, Liu D, Martin J, Tang XM, Lee JJ, El-Naggar AK., Wistuba I, Culotta KS, Mao L, Gillenwater A, Sagesaka YM, Hong WK, Papadimitrakopoulou V. Phase II randomized, placebo-controlled trial of green tea extract in patients with high-risk oral premalignant lesions. Cancer prevention research (Philadelphia, Pa.). 2009;2(11):931-41. doi: 10.1158/1940-6207.CAPR-09-0121.
29. Maysarah H, Faradilla M, Sari I, Illian DN. Cancer Chemopreventive effect of Rodent Tuber (Typhonium flagelliforme (Lood) Bl) against DMBA-Induced Rats Breast Tumor. Research Journal of Pharmacy and Technology. 2020; 13(12):5811-5815. doi: 10.5958/0974-360X.2020.01013.6
30. Hemalatha CN, Anbarasu K, Vijey Aanandhi M. Evaluation of Anti-Cancer and Anti-Oxidant Activity of Cissus quandrangularis Extracts in DMBA induced Mammary Carcinomas. Research Journal of Pharmacy and Technology. 2017; 10(1): 293-300. doi: 10.5958/0974-360X.2017.00060.9
31. Saha D, Hait M. An Ontological Design: Two Stage Mouse Skin Carcinogenesis Induced By DMBA and Promoted By Croton Oil. Asian Journal of Research in Pharmaceutical Sciences. 2012; 2(1): 01-03.
32. Choi J, Gyamfi J, Jang H, and Koo JS. The role of tumor-associated macrophage in breast cancer biology. Histology and Histopathology. 2018;33(2):133-145. doi: 10.14670/HH-11-916.
33. Saldana JI. Macrophages. Available on https://www.immunology.org/public-information/bitesized-immunology/cells/macrophages. 2021.
34. Efendi Z. Phagocytic Power of Macrophages in Loose Tissues of the Body. Faculty of Medicine, Univ of North Sumatra, North Sumatra. 2003.
35. Muzakki NA. Book of Life: Chrysanthemum X morifolium. Indonesian University of Education, Bandung. 2017.
36. Pan X, Xu G, Zhou X, Shen R, Hu B. Inhibition Effects of Human Gastric Carci-Noma SGC-7901 Cells on Chrysanthemum Flavonoids In Vivo. Procedia Engineering. 2011;18:139–44. doi: 10.1016/j.proeng.2011.11.022
37. Makiyah SNN, Wardhani UH. Potential of Citrullus lanatus Fruit Ethanol Extract as Immunosuppressive Agent through Spleen Histology Observation of BALB/c Mice. Majalah Kedokteran Bandung. 2017;49(4):245–51.
38. Ren W, Qiao Z, Wang H, Zhu L, Zhang L. Flavonoids: Promising Anticancer Agents. Med. Res. Rev. 2003;23(4):519–34. doi: 10.1002/med.10033.
39. Cox-Georgian D, Ramadoss N, Dona C, Basu C. Therapeutic and Medicinal Uses of Terpenes. Medicinal Plants. 2019;12: 333–359. doi: 10.1007/978-3-030-31269-5_15
40. Thoppil RJ, Bishayee A. Terpenoids As Potential Chemopreventive and Therapeutic Agents in Liver Cancer. World Journal of Hepatology. 2011;3(9):228-249. doi: 10.4254/wjh.v3.i9.228
41. Bilal M, Al-Saleh J, Fakher FA. Serum levels of prostaglandin E2 (PGE2) and interleukin 17 (IL-17) are associated with Angiogenesis and Metastasis in breast cancer patients. Research Journal of Pharmacy and Technology. 2021;14(1):317-320. doi: 10.5958/0974-360X.2021.00058.5
42. Kelepouri D, Mavropoulos A, Bogdanos DP, Sakkas LI. The Role of Flavonoids In Inhibiting Th17 Responses In Inflammatory Arthritis. Journal of Immunology Research. 2018;2018:1-11. doi: 10.1155/2018/9324357
43. Singh RP, Agarwal R. Natural Flavonoids Targeting Deregulated Cell Cycle Progression In Cancer Cells. Current drug target. 2006;7(3):345–54. doi: 10.2174/138945006776055004.
44. Gonçalves ECD, Baldasso GM, Bicca MA, Paes RS, Capasso R, Dutra RC. Terpenoids, Cannabimimetic Ligands, Beyond The Cannabis Plant. Molecules. 2020;25(7):1–47. doi: 10.3390/molecules25071567
45. Kim JW, Han JY, Hong JT, Li R, Eun JS, Oh KW. Ethanol Extract of The Flower Chrysanthemum morifolium Augments Pentobarbital-Induced Sleep Behaviors: Involvement of Cl− Channel Activation. Evidence-based complementary and alternative medicine : eCAM. 2011;2011:1-7. doi:10.1155/2011/109164.
46. Li L, Gu L, Chen Z, Wang R, Ye J, Jiang H. Toxicity Study Of Ethanolic Extract Of Chrysanthemum morifolium In Rats. Journal of food science. 2010;75(6):T105–9. doi: 10.1111/j.1750-3841.2010.01702.x.
47. Ye JF, Li LP, Gu LQ, Wang RW, Jiang HD. Pharmacokinetics of Luteolin And Apigenin In Rats After Single Oral Administration Of Chrysanthemum morifolium Extract At The Dose Of Effectiveness And Approximate To The Maximal Tolerance. Journal of Chinese Pharmaceutical Sciences. 2011;46(3):214-218.