CLAUSENA EXCAVATA YAPRAK FRAKSİYONLARININ BAĞIŞIKLIK HÜCRELERİNDE REAKTİF OKSİJEN TÜRLERİNİN ÜRETİMİNİ AZALTARAK GÖSTERDİĞİ IMMÜNOMODÜLATÖR ETKİNLİK

Abstract

Amaç: Clausena excavate’ın anti-enflamatuvar etkinlik gösterdiği bilinmektedir. Bununla birlikte, bu özelliği, bağışıklık hücrelerine hangi mekanizma ile etki ettiği ve reaktif oksijen türlerinin (ROS) üretimini baskıladığı araştırılmamıştır.
Gereç ve Yöntem: Bu çalışmada, C. excavate yapraklarının etil asetat, petrol eteri, kloroform ve methanol ekstrelerinin tam kan, polimorfonkleer (PMN) hücreler ve makrofajlardan ROS üretimini azaltarak gösterdikleri immunomodülatör etki değerlendirilmiştir.
Sonuç ve Tartışma: Test edilen fraksiyonlar arasından, C. excavate etil asetat ekstrresi en güçlü antienflamatuvar etkiyi göstermiş ve zimosan ve PMA tarafından active edilmiş tam kan, PMN ve makrofaj hücrelerinde, intraselüler ve ekstraselüler fagositik oksidatif ROS üretimini anlamlı oranda (p < 0.001) baskılamış ve %50 inhibisyon konsantrasyonları (IC50) sırasıyla 5.7 ± 0.01, 1.3 ± 0.01, and 0.7 ± 0.03 µg/mL olarak tespit edilmiştir. Bu çalışma, bitkinin antienflamatuvar aktivitesinin mekanizması ve çeşitli enflamatuvar rahatsızlıkların tedavisinde kullanımına dair bilgi sağlamaktadır.

Keywords

• Clausena excavata
• enflamasyon
• makrofaj
• ROS

IMMUNOMODULATORY POTENTIAL OF CLAUSENA EXCAVATA LEAVES FRACTIONS VIA DECREASING THE PRODUCTION OF REACTIVE OXYGEN SPECIES FROM IMMUNE CELLS

Abstract

Objective: Clausena excavata is known to possess anti-oxidant property. However, this property through which mechanism it affects the immune cells and suppresses the production of reactive oxygen species (ROS) has not been explored.
Material and Method: This study evaluated the immunomodulatory activities of ethyl acetate, petroleum ether, chloroform, and methanol C. excavata leaf extracts by decreasing the production of ROS from whole blood, polymorphonuclears (PMNs) cells and macrophages.
Result and Discussion: Among the fractions tested, ethyl acetate C. excavate extract (EACE) showed potent anti-oxidant property and significantly (p < 0.001) suppressed intracellular and extracellular phagocytic oxidative ROS burst produced by the zymosan and PMA-activated whole blood, PMNs, and macrophages cells with 50% inhibitory concentration (IC50) values of 5.7 ± 0.01, 1.3 ± 0.01, and 0.7 ± 0.03 µg/mL respectively. This study provides information regarding the mechanism behind its anti-oxidant property and its herbal use in treating various higher oxidative stress associated diseases.

Keywords

• Clausena excavata
• Inflammation
• Macrophage
• ROS

References

1. 1. Bryan, N., Ahswin, H., Smart, N., Bayon, Y., Wohlert, S., Hunt, J.A. (2012). Reactive oxygen species (ROS) –a family of fate deciding molecules pivotal in constructive inflammation and wound healing. European Cells and Materials, 24(249), e65. [CrossRef]
2. 2. Albaayit, S.F.A., Al-Khafaji, A.S.K., Alnaimy, H.S. (2019). In vitro macrophage nitric oxide and interleukin-1 beta suppression by Moringa peregrina seed. Turkish Journal of Pharmaceutical sciences. 16(3), 362–365. [CrossRef]
3. 3. Poljsak, B. (2011). Strategies for reducing or preventing the generation of oxidative stress. Oxidative medicine and cellular longevity, 2011. [CrossRef]
4. 4. Albaayit, S.F.A., Abdullah, R., Abdullah, N. (2020). Zerumbone-loaded nanostructured lipid carrier gel facilitates wound healing in rats. Revista Brasileira de Farmacognosia, 30(2), 272–278. [CrossRef]
5. 5. Mohammed, E. S., Al-Taie, W. F., Numan, I. T., Hussain, S. A. (2012). Changes in Serum Levels of Tumor Necrosis Factor-Alpha and Antioxidant status in Different Stages of Malignant Prostate Cancer Patients in Iraq. Iraqi Journal of Pharmaceutical Sciences, 21(1), 56-60. [CrossRef]
6. 6. Ali, S. H., Hamadi, S. A., Al-Jaff, A. N. (2007). Effect of ergotamine and its combination with vitamin E or melatonin on total antioxidant status in migraine patients. Iraqi Journal of Pharmaceutical Sciences, 16(2), 27-33. [CrossRef]
7. 7. Manosroi, A., Saraphanchotiwitthaya, A., Manosroi, J. (2003). Immunomodulatory activities of Clausena excavata Burm. f. wood extracts. Journal of Ethnopharmacology, 89(1), 155–160. [CrossRef]
8. 8. Rahman, M.T., Alimuzzaman, M., Shilpi, J.A., Hossain, M.F. (2002). Antinociceptive activity of Clausena excavata leaves. Fitoterapia, 73(7-8), 701–703. [CrossRef]

9. 9. Huang, L., Zhe-Ling, F.E.N.G., Yi-Tao, W.A.N.G., Li-Gen, L.I.N. (2017). Anticancer carbazole alkaloids and coumarins from Clausena plants: A review. Chinese journal of natural medicines, 15(12), 881–888. [CrossRef]
10. 10. Albaayit, S.F.A., Rasedee, A., Abdullah, N., Abba, Y. (2020). Methanolic extract of Clausena excavata promotes wound healing via antiinflammatory and anti-apoptotic activities. Asian Pacific Journal of Tropical Biomedicine, 10(5), 232-238. [CrossRef]
11. 11. Albaayit, S.F.A., Khan, M., Rasedee, A., Noor, M.H.M. (2021). Ethyl acetate extract of Clausena excavata induces growth inhibition of non-small-lung cancer, NCI-H460, cell line via apoptosis. Journal of Applied Biomedicine, 19(1), 40–47. [CrossRef]
12. 12. Orhan, I. E., Mesaik, M. A., Jabeen, A., & Kan, Y. (2016). Immunomodulatory properties of various natural compounds and essential oils through modulation of human cellular immune response. Industrial crops and products, 81, 117-122. [CrossRef]
13. 13. Albaayit, S.F.A., Maharjan, R. (2018). Immunomodulation of zerumbone via decreasing the production of reactive oxygen species from immune cells. Pakistan Journal of Biological Sciences, 21(9), 475–479. [CrossRef]
14. 14. Majdalawieh, A.F., Fayyad, M.W. (2015). Immunomodulatory and anti-inflammatory action of Nigella sativa and thymoquinone: A comprehensive review. International immunopharmacology, 28(1), 295–304. [CrossRef]
15. 15. Albaayit, S.F.A. (2021). Evaluation of anti-methicillin resistant Staphylococcus aureus property of Clausena excavata leaves by using atomic force microscopy and flowcytometry techniques. Pakistan Journal of Agricultural Sciences, 58(1), 315–320. [CrossRef]
16. 16. Albaayit, S.F.A., Maharjan, R., Khan, M. (2021). Evaluation of hemolysis activity of Zerumbone on RBCs and brine shrimp toxicity. Baghdad Science Journal, 18(1), 65–69. [CrossRef]
17. 17. Al-Bahrani, R. M., Radif, H. M., Albaayit, S. F. A. (2020). Evaluation of potent silver nanoparticles production from Agaricus bisporus against Helicobacter pylori. Pakistan Journal of Agricultural Sciences, 57(4), 1197–1201. [CrossRef]
18. 18. Albaayit, S. F. A., Mariam, K. H. A. N., & Abdullah, R. (2021). Zerumbone induces growth inhibition of Burkitt’s lymphoma cell line via apoptosis. Natural Volatiles and Essential Oils, 8(3), 56-63. [CrossRef]
19. 19. Al-Ani, L. K. T., Yonus, M. I., Mahdii, B. A., Omer, M. A., Taher, J. K., Albaayit, S. F. A., Al-Khoja, S. B. (2018). First record of use Fusarium proliferatum fungi in direct treatment to control the adult of wheat flour Tribolium confusum, as well as, use the entomopathogenic fungi Beauveria bassiana. Ecology, Environment and Conservation, 24(3), 29-34.
20. 20. Albaayit, S. F. A. (2021). Enzyme inhıbıtory propertıes of zerumbone. Pakistan Journal of Agricultural Sciences, 58(3), 1207-1209. [CrossRef]
21. 21. Albaayit, S.F.A. (2020). In Vitro Evaluation of Anticancer Activity of Moringa Peregrina Seeds on Breast Cancer Cells. The Eurasia Proceedings of Science Technology Engineering and Mathematics, 11,163-166. http://www.epstem.net/en/pub/issue/58065/838264.
22. 22. Albaayit, S.F.A., Maharjan, R., Abdullah, R., Noor, M.H.M. (2022). Evaluation of anti-methicillin-resistant Staphylococcus aureus property of zerumbone. Journal of Applied Biomedicine, 20(1), 22–36.
23. 23. Albaayit, S. F. A., Abba, Y., Abdullah, R., & Abdullah, N. (2016). Prophylactic effects of Clausena excavata Burum. f. leaf extract in ethanol-induced gastric ulcers. Drug design, development and therapy.
24. 24. Albaayit, S. F. A., Abba, Y., Abdullah, R., & Abdullah, N. (2015). Effect of Clausena excavata Burm. f.(Rutaceae) leaf extract on wound healing and antioxidant activity in rats. Drug design, development and therapy.
25. 25. Yahfoufi, N., Alsadi, N., Jambi, M., Matar, C. (2018). The immunomodulatory and anti-inflammatory role of polyphenols. Nutrients, 10(11), 1618. [CrossRef]
26. 26. Das, J., Ramani, R., Suraju, M.O. (2016). Polyphenol compounds and PKC signaling. Biochimica et Biophysica Acta (BBA)-General Subjects, 1860(10), 2107–2121. [CrossRef]
27. 27. Albaayit, S. F. A., Maharjan, R., Abdullah, R., Noor, M. H. M. (2021). Anti-Enterococcus Faecalis, Cytotoxicity, Phytotoxicity, and Anticancer Studies on Clausena excavata Burum. f.(Rutaceae) Leaves. BioMed Research International, 2021. [CrossRef]
28. 28. Ahmad, Z., Hassan, S.S., Azim, S. (2017). A therapeutic connection between dietary phytochemicals and ATP synthase. Current medicinal chemistry, 24(35), 3894–3906. [CrossRef]
29. 29. Pérez-Lara, Á., Corbalán-García, S., & Gómez-Fernández, J. C. (2011). Curcumin modulates PKCα activity by a membrane-dependent effect. Archives of biochemistry and biophysics, 513(1), 36-41. [CrossRef]
30. 30. Menard, C., Bastianetto, S., & Quirion, R. (2013). Neuroprotective effects of resveratrol and epigallocatechin gallate polyphenols are mediated by the activation of protein kinase C gamma. Frontiers in cellular neuroscience, 7, 281. [CrossRef]
31. 31. Ferriola, P. C., Cody, V., & Middleton Jr, E. (1989). Protein kinase C inhibition by plant flavonoids: kinetic mechanisms and structure-activity relationships. Biochemical pharmacology, 38(10), 1617-1624. [CrossRef]
32. 32. Mishra, S., & Vinayak, M. (2015). Role of ellagic acid in regulation of apoptosis by modulating novel and atypical PKC in lymphoma bearing mice. BMC Complementary and Alternative Medicine, 15(1), 1-8. [CrossRef]
33. 33. Szaefer, H., Kaczmarek, J., Rybczyńska, M., & Baer-Dubowska, W. (2007). The effect of plant phenols on the expression and activity of phorbol ester-induced PKC in mouse epidermis. Toxicology, 230(1), 1-10. [CrossRef]
34. 34. Tanruean, K., Poolprasert, P., Suwannarach, N., Kumla, J., & Lumyong, S. (2021). Phytochemical Analysis and Evaluation of Antioxidant and Biological Activities of Extracts from Three Clauseneae Plants in Northern Thailand. Plants, 10(1), 117. [CrossRef]
35. 35. Albaayit, S. F. A., Abba, Y., Abdullah, R., & Abdullah, N. (2014). Evaluation of antioxidant activity and acute toxicity of Clausena excavata leaves extract. Evidence-Based Complementary and Alternative Medicine. [CrossRef]
36. 36. Elumalai, K., & Id, K. (2016). Antioxidant activity and phytochemical screening of different solvent extracts Clausena excavata burm F. Rutaceae) MOJ Ecology & Environmental Sciences, 1(1), 1. [CrossRef]