Lymphocyte Cell Proliferation Profile of Benalu Batu (Begonia medicinalis) from the North Morowali Regency Central Sulawesi Province

  • Akhmad Khumaidi Jurusan Farmasi, FMIPA Universitas Tadulako
  • Agustinus Widodo Jurusan Farmasi, FMIPA Universitas Tadulako
  • Arsa Wahyu Nugrahani Jurusan Farmasi, FMIPA Universitas Tadulako
  • Ediati Sasmito Bagian Kimia Fakultas Farmasi Universitas Gadjah Mada
  • Nanang Fakhrudin Bagian Biologi Fakultas Farmasi Universitas Gadjah Mada

Abstract

The plant of Benalu Batu (Begonia medicinalis) from the North Morowali regency has been used empirically and is known to have anticancer activity. The study aims to determine the profile of the activity of lymphocytes cell proliferation of extracts and fractions of Benalu Batu in vitro as well to measure the correlation of total flavonoid content against the stimulating index of lymphocytes cell proliferation. The extraction of simplicia by using the maceration method with methanol solvent. The liquid-liquid partition method is used in the fractionation of methanol extracts with hexane, ethyl acetate, and water solvents, sequentially. Test of lymphocytes cell proliferation using MTT reduction (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method with concentration series 10, 20, 50, and 100 μg/mL. The total of flavonoids content of extracts and fractions were determined by using colorimetric method. The stimulation index (IS) is used in measuring the activity of lymphocytes cell proliferation. The test results showed that the methanol extracts, hexane fraction, ethyl acetate, and water may increase the proliferation of lymphocytes in the entire test concentration. The concentration of test influences on increasing the stimulation of the proliferation of lymphocytes cells. A test concentration of 100 μg/mL has the highest stimulation index on each test sample and its stimulant index value of hexane fraction, ethyl acetate fraction, methanol fraction and water fraction were 10.12, 6.56, 4.82, and 4.17, respectively. Total flavonoids content and stimulation indices have very low correlation (r = 0,082) and concentrations of 10 μg/mL have the highest correlation coefficient (r2 = 0.18). The results showed that the hexane and ethyl acetate fractions can be developed as immunostimulant materials for the anticancer supportive therapeutic agents despite having a very low correlation to the flavonoid levels.

References

1. Ardi WH, Zubair SM , Ramadanil & Thomas DC. Begonia medicinalis (Begoniaceae), a new species from Sulawesi, Indonesia. Phytotaxa. 2019. 423(1):041–045. http://dx.doi.org/10.11646/phytotaxa. 423.1.5.

2. Anam S, Yuliet, Ritna A, Dwimurti F, Rismayanti D, Zubair, MS. Aktivitas sitotoksik ekstrak metanol benalu batu (Begonia sp.) : ethnomedicine Suku Wana Sulawesi Tengah. Jurnal Ilmu Kefarmasian Indonesia. 2014. 12(1):10-16. http://jifi.farmasi.univpancasila.ac.id/index.php/jifi/article/view/176.

3. Zubair MS, Anam S, Khumaidi A, Susanto Y, Hidayat M, & Ridhay A. Molecular docking approach to identify potential anticancer compounds from Begonia (Begonia sp). AIP Conference Procidings. 2016. 1755(1):1-7. https://doi.org/10.1063/1.4958513.

4. Venkatesha SH, Astry B, Nanjundaiah SM, Kim HR, Rajaiah R, Yang Y, Tong L, Yu H, Berman BM, Moudgil KD. Review : Control of autoimmune arthritis by herbal extracts and their bioactive components. Asian Journal of Pharmacetical Science. 2016. 11(2):301-307. https://doi.org/10.1016/ j.ajps.2016.02.003.

5. Zhang H, Chen J. Current status and future directions of cancer immunotherapy. Journal of Cancer. 2018. 9(10):1773-1781. doi: 10.7150/jca.24577.

6. Ménétrier-Caux C, Ray-Coquard I, Blay JY & Caux C. Lymphopenia in cancer patients and its effects on response to immunotherapy: an opportunity for combination with cytokines?. Journal for Immuno Therapy of Cancer. 2019. 7 (1): 1-15. http://dx.doi.org/10.1186/s40425-019-0549-5.

7. Mikhaeil BR, Badria FA, Maatooq GT, & Ameer MA. Antioxidant and immunomodulatory constituens of henna leaves. Zeitschrift fur Naturforschung. C, Journal of Biosciences. 2004. 59(7-8):468-476. http://doi.org/10.1515/znc-2004-7-803.

8. Khumaidi A, Hertiani T, & Sasmito E. Analisis korelasi antara efek proliferasi limfosit dengan kandungan fenolik dan flavonoid subfraksi etil asetat Myrmecodia tuberosa (Non Jack) Bl. secara in vitro pada mencit BALB/c. Jurnal Ilmu Kefarmasian Indonesia. 2015. 13(1): 102-107. http://jifi.farmasi.univpancasila.ac.id/index.php/jifi/article/view/132.

9. Huang CF, Lin SS, Liao PH, Young SC, & Yang CC. The immunopharmaceutical effects and mechanism on herb medicine. Cellular & Molecular Immunology. 2008. 5(1):23-31. http://www.cmi.ustc.edu.cn/5/1/23.pdf.

10. Hertiani T, Sasmito E, Sumardi, & Ulfah M. Preliminary studi on immunomodulatory effect of sarang semut tubers Myrmecodia tuberosa and Myrmecodia pendens. On Line Journal of Biological Sciences. 2010. 10(3):136-141. doi : 10.3844/ojbsci.2010.136.141. https://thescipub.com/abstract/10.3844/ojbsci. 2010.136.141.

11. Saraphanchotiwitthaya A, Ingkaninan K, & Sripalakit P. 2007. Immunomodulating activity of thai rejuvenating plants. Naresuan University Journal. 2007.15(3):149-157.

12. Chang CC, Yang MH, Wen HM, & Chern JC. Estimation of total flavonoid content in propolis by two complementary colorimetric methods. Journal of Food and Drug Analysis. 2002. 10(3):178-182.

13. Munawaroh R, Siswadi, Setyowati EP, Murwanti R, & Hertiani T. Correlation between total flavonoid contents and macrophage phagocytosis activity of fractions from faloak (Sterculia quadrifida R.Br.) barks ethanolic extract in vitro. Traditional Medicine Journal. 2018. 23(1):47-55. https://doi.org/ 10.22146/mot.30882.

14. Do QD, Angkawijaya AE, Tran-Nguyen PL, Huynh LH, Soetaredjo FE, Ismadji S, & Ju Y. Effect of extraction solvent on total phenol content, total flavonoid content, and antioxidant activity of limnophila aromatica. Journal of Food and Drug Analysis. 2014. 22(3):296-302. https://doi.org/10.1016/ j.jfda.2013.11.001.

15. Nastiti K, Sudarsono, & Nugroho AE. Evaluation of in vitro immunomodulatory effect of fractions of Ficus septica Burm. F. and their total flavonoid and phenolic contents. International Food Research Journal. 2014. 21(5):1981-1987.

16. Schober P, Boer C, & Schwarte LA. Correlation coefficients: appropriate use and interpretation. Anesthesia & Analgesia. 2018. 126 (5):1763-1768. https://doi.org/10.1213/ANE.0000000000002864.

17. Akoglu H. User's guide to correlation coefficients. Turkish Journal of Emergency Medicine. 2018. 18(3):91-93. https://doi.org/10.1016/j.tjem.2018.08.001.

18. Rohman A, Riyanto S, & Hidayati NK. Aktivitas antioksidan, kadar fenolik total, dan flavonoid total daun mengkudu (Morinda citrifolia L.). Agritech. 2007. 27(4):147- 151.

19. Chiang LC, Ng LT, Chiang W, Chang MY, & Lin CC. Immunomodulatory activities of flavonoids, monoterpenoids, triterpenoids, iridoid glycosides and phenolic compounds of plantago species. Planta Med. 2003. 69(7):600-604.

20. Ilina T, Kashpur N, Granica S, Bazylko A, Shinkovenko I, Kovalyova A, Goryacha O, & Koshovyi O. Phytochemical profiles and in vitro immunomodulatory activity of ethanolic extracts from Galium aparine L. Plants. 2019, 8(12):541(1-13).https://doi.org/10.3390/plants8120541.

21. Ayatollahi AM, Ghanadian M, Afsharypour S , Abdella OM, Mirzai M, & Askari G. Pentacyclic triterpenes in Euphorbia microsciadia with their T-cell proliferation activity. Iranian Journal of Pharmaceutical Research. 2011. 10(2): 287-294.

22. Rios JL. Effect of triterpenes on the immune system. Journal of Ethnopharmacology. 2010. 128(1):1-14. https://doi.org/10.1016/j.jep.2009.12.045.

23. Cholakova M, Christov V, Dimitrova D, Evstatieva L, Alexandrova R, Nikolova E. Flavonoid and terpenoid isolated from Loranthus europaeus with stimulatory effect on lymphocyte proliferation. Experimental Pathology and Parasitology. 2002. 5(9):45-48.

24. Moiteiro C, Justino F, Tavares R, Marcelo Curto MJ, Florencio MH, Nascimento M, Pedro M, Cerqueira F, Pinto MM. Synthetic secofriedelane and friedelane derivatives as inhibitor of human lymphocyte proliferation and growth of human cancer cell lines in vitro. Journal of Natural Products. 2001. 64(10): 1273-1277.

25. Arokiyaraj S, Perinbam K, Agastian P, Balaraju K. Immunosuppresive effect of medicinal plants of kolli hills on mitogen-stimulated proliferation of the human peripheral blood mononuclear cells in vitro. Indian Journal of Pharmacology. 2007. 39(4):180-183. doi: 10.4103/0253-7613.36535.

26. Chiang LC, Ng LT, Chiang W, Chang MY, & Lin CC. Immunomodulatory activities of flavonoids, monoterpenoids, triterpenoids, iridoid glycosides and phenolic compounds of plantago species. Planta Med. 2003. 69(7):600-604. https://doi.org/10.1055/s-2003-41113.

27. Middleton JRE, Kandaswami C, & Theoharides TC. Review : the effect of plant flavonoids on mammalian cells : implication for inflammation, heart disease, and cancer. Pharmacological Reviews. 2000. 52(4)673-751.

28. Hosseinzade A, Sadeghi O, Biregani AN, Soukhtehzari S, Brandt GS, & Esmaillzadeh A. Immunomodulatory effects of flavonoids: possible induction of T CD4+ regulatory cells through suppression of mTOR pathway signaling activity. Frontiers in Immunology. 2019. 10(51):1-12. https://doi.org/10.3389/fimmu.2019.00051.

29. Saxton RA, & Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell. 2017. 168(6): 960-976. https://doi.org/10.1016/j.cell.2017.02.004.

30. Wang L, Li C, Lin Q, Zhang X, Pan H, Xu L, Shi Z, Ouyang D, & He X. Cucurbitacin E suppresses cytokine expression in human Jurkat T cells through down-regulating the NF-κB signaling. Acta Biochim Biophys Sin. 2015. 47(6): 459–465. https://doi.org/10.1093/abbs/gmv030.

31. Rasheed A, & Qasim M. A review of natural steroids and their applications. International Journal of Pharmaceutical Science and Research. 2013. 4(2): 520-531. http://dx.doi.org/10.13040/IJPSR.0975-8232.4(2).520-31.
Published
2020-04-25
How to Cite
KHUMAIDI, Akhmad et al. Lymphocyte Cell Proliferation Profile of Benalu Batu (Begonia medicinalis) from the North Morowali Regency Central Sulawesi Province. JURNAL ILMU KEFARMASIAN INDONESIA, [S.l.], v. 18, n. 1, p. 61-67, apr. 2020. ISSN 2614-6495. Available at: <http://jifi.farmasi.univpancasila.ac.id/index.php/jifi/article/view/785>. Date accessed: 25 apr. 2024. doi: https://doi.org/10.35814/jifi.v18i1.785.
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