Effect of Kaempferol in Medicinal Plants on LPS-induced THP-1 Macrophages

Abstract

Introduction: Inflammation is a biological response of the immune system when triggered by various factors including toxic compounds, damaged cells and pathogens. Active substances isolated from medicinal plants should be chosen carefully when using them as a new therapeutic strategy in the treatment of inflammatory diseases. Kaempferol is a polyphenol abundantly found in medicinal plants, vegetables, fruits. Kaempferol has anti-cancer, anti-viral, anti-bacterial properties.
Aim: The aim of this study is to examine the effect of kaempferol on NO and PGE2 levels, which are target molecules in studies for the treatment of inflammation, and cell viability in LPS-induced THP-1 macrophage cells.
Result: In 2022, Kaempferol was applied to LPS-induced THP-1 macrophage cells at a concentration of 2.5, 5, 7.5, 10 µM. Kaempferol administration to THP-1 macrophage cells did not affect cell viability and also decreased PGE2 and NO % levels. It was determined that administration of kaempferol at different doses did not decrease cell viability in THP-1 macrophage cells. In addition, in THP-1 macrophage cells induced by LPS, 2.5 µM kaempferol application decreased NO % level and 7.5 µM kaempferol application decreased PGE2 level statistically.
Discussion and Conclusion: The application of 7.5 µM kaempferol does not have a negative effect on the proliferation of macrophage cells, but decreases both NO level and PGE2 order and shows good anti-inflammatory effect.

Keywords

• Kaempferol
• THP-1,
• Macrophage
• NO,
• PGE2
• LPS

Tıbbi Bitkilerde Bulunan Kaempferol’ün LPS ile İndüklenmiş THP-1 Makrofajları Üzerine Etkisi

Abstract

Giriş: İnflamasyon, immün sisteminin toksik bileşikler, hasarlı hücreler ve patojenlerinde içinde yer aldığı çeşitli faktörler ile tetiklediğinde verdiği biyolojik bir cevaptır. Tıbbi bitkilerden izole edilen etkin maddeler, inflamatuar hastalıkların tedavisinde yeni bir terapötik strateji olarak kullanılırken dikkatle seçilmelidir. Kaempferol tıbbi bitkilerde sebzelerde meyvelerde bolca bulunan bir polifenoldur. Kaempferol anti-kanser, anti-viral, anti-bakteriyel özelliklere sahiptir.
Amaç: Bu çalışmada amaç LPS ile indüklenmiş THP-1 makrofaj hücrelerinde kaempferolün hücre canlılığı ve inflamasyonun tedavisi için yapılan çalışmalarda hedef molekül olan NO ve PGE2 düzeyleri üzerine etkisini incelemektir.
Bulgular: 2022 yılında yapmış olduğumuz çalışmada LPS ile indüklenmiş THP-1 makrofaj hücrelerine 2,5, 5, 7,5, 10 µM konsantrasyonunda kaempferol uygulandı. Hücre canlılığı, PGE2 düzeyi ve NO üretimi incelendi. Farklı dozlarda kaempferol uygulaması THP-1 makrofaj hücrelerinde hücre canlılığını azaltmadığı belirlendi. Ayrıca LPS ile indüklenen THP-1 makrofaj hücrelerinde 2,5 µM kaempferol uygulaması % NO düzeyini ve 7,5 µM kaempferol uygulaması PGE2 düzeyini istatistiksel olarak anlamlı azaltmıştır.
Tartışma ve sonuç: 7,5 µM kaempferol uygulaması makrofaj hücrelerinin proliferasyonu negatif etki göstermeyip hem NO düzeyini hemde PGE2 düzeni azaltıp iyi anti inflamatuvar etki göstermektedir.
 

Keywords

• Kaempferol
• THP-1
• Makrofaj
• NO
• PGE2
• LPS
• Macrophage

Supporting Institution

Destek almamıştır

Thanks

Hücre kültürü çalışmalarından dolayı Marijas Jurisic’e teşekkür ederiz. Laboratuvarında doktora sonrası çalışmalarına izin verdiği için Prof. Dr. Marc SCHNEIDER’e teşekkür ederiz.

References

1. 1. Silva Dos Santos J, et al. The pharmacological action of kaempferol in central nervous system diseases: A Review. Frontiers in Pharmacology 2020; 11:565700.
2. 2. Bangar SP, et al. Kaempferol: A flavonoid with wider biological activities and its applications. Critical Reviews in Food science and nutrition 2022; 1-25.
3. 3. Nagarajan, S. Polyphenolic compounds - a promising leads for antiviral therapy. Pharmacophore 2021;31(1):36-47.
4. 4. Golli R, Thummaneni C, Vangalapati M. Green synthesis and characterization for the extraction of kaempferol from Brassica oleracea var. italica - Antibacterial activity. Mater today 2022;62:3457-61.
5. 5. Chang SQ, et al. Kaempferol exerts a neuroprotective effect to reduce neuropathic pain through TLR4/NF-kappa B signaling pathway. Phytotherapy Research 2022;36(4):1678-91.
6. 6. Karadag A. Türkiye’deki bazı tıbbi ve aromatik bitkilerin antioksidan potansiyelleri ve fenolik kompozisyonları. Avrupa Bilim ve Teknoloji Dergisi 2019;16: 631-37.
7. 7. Şekeroglu N, Gezici, S. Türkiye’nin virüs savar bitkisi Laden (Cistus spp.) türleri: Geleneksel kullanımları, biyoaktif kimyasal bileşenleri ve farmakolojik aktiviteleri. Mersin Üniversitesi Tıp Fakültesi Lokman Hekim Tıp Tarihi Ve Folklorik Tıp Dergisi 2021;11(2): 258-268.
8. 8. Calderon-Montano J.M, et al. A review on the dietary flavonoid kaempferol. Mini-reviews in medicinal chemistry 2011;11(4):298-344.

9. 9. Lund ME, et al. The choice of phorbol 12-myristate 13-acetate differentiation protocol influences the response of THP-1 macrophages to a pro-inflammatory stimulus. Journal of Immunological Methods 2016;430:64-70.
10. 10. Tedesco, S., et al. Convenience versus biological significance: are PMA-differentiated THP-1 cells a reliable substitute for blood-derived macrophages when studying in vitro polarization?. Frontiers in Pharmacology 2018;9:71.
11. 11. Maldonado RF, Sa-Correia I, Valvano MA. Lipopolysaccharide modification in Gram-negative bacteria during chronic infection. FEMS Microbiology Reviews 2016;40(4):480-93.
12. 12. Yildirim M, et al. Anti-Inflammatory effects of Coumarin-Selenophene derivatives on LPS-Stimulated RAW 264.7 macrophage cells. Russian journal of bioorganic chemistry 2022,
13. 13. Altinoz MA, Elmaci I. Targeting nitric oxide and NMDA receptor-associated pathways in treatment of high grade glial tumors. Hypotheses for nitro-memantine and nitrones. Nitric oxide: Chemistry and Biology 2018;79:68-83.
14. 14. Stachlewitz R, et al. Role of nitric oxide and peroxynitrite production in the development of inflammatory injury in a rat model of periodontal disease. Portland Press 2000;16:192.
15. 15. Sharma JN, Al-Omran A, Parvathy SS. Role of nitric oxide in inflammatory diseases. Inflammopharmacology 2007;15(6):252-59.
16. 16. Medeiros A, et al. Prostaglandin E2 and the suppression of phagocyte innate immune responses in different organs. Mediators of Inflammation 2012;2012:327568.
17. 17. Yuan J, et al. Gold clusters attenuate ınflammation in rat mesangial cells via inhibiting the activation of NF-kappaB pathway. Nanomaterials 2020;10(4):712.
18. 18. Tang T, et al. Macrophage responses to lipopolysaccharide are modulated by a feedback loop involving prostaglandin E2, dual specificity phosphatase 1 and tristetraprolin. Scientific Reports 2017;7(1): 4350.
19. 19. Suliburk JW, et al. Ketamine attenuates liver injury attributed to endotoxemia: role of cyclooxygenase-2. Surgery 2005;138(2):134-140.
20. 20. Alam W, et al. Kaempferol as a dietary anti-inflammatory agent: current therapeutic standing. Molecules 2020;25(18).
21. 21. Zhang XX, et al. Flavonoid Apigenin ınhibits lipopolysaccharide-induced inflammatory response through multiple mechanisms in macrophages. Plos One 2014;9(9).
22. 22. Cirmi S, et al. Oleacein attenuates lipopolysaccharide-ınduced ınflammation in THP-1- derived macrophages by the ınhibition of TLR4/MyD88/NF-kappa B pathway dagger. International Journal of Molecular Sciences 2022;23(3):1206.
23. 23. Abd Allah HN, et al. Melissa officinalis L. ameliorates oxidative stress and inflammation and upregulates Nrf2/HO-1 signaling in the hippocampus of pilocarpine-induced rats. Environ Sci Pollut Res Int 2022;29(2):2214-2226.
24. 24. Kim BH, et al. Down-regulatory effect of quercitrin gallate on nuclear factor-kappa B- dependent inducible nitric oxide synthase expression in lipopolysaccharide-stimulated macrophages RAW 264.7. Biochemical Pharmacology 2005;69(11):1577-83.
25. 25. Garcia-Mediavilla V, et al. The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor kappaB pathway in Chang Liver cells. European Journal of Pharmacology 2007;557(2-3):221-29.
26. 26. Kim CJ, et al. The effects of Kaempferol-Inhibited autophagy on osteoclast formation. International Journal of Molecular Sciences 2018;19(1):125.
27. 27. Li, XY, et al. Kaempferol suppresses lipid accumulation in macrophages through the downregulation of cluster of differentiation 36 and the upregulation of scavenger receptor class B type I and ATP-binding cassette transporters A1 and G1. International Journal of Molecular Medicine 2013;31(2), 331-338.
28. 28. Park SE, et al. Kaempferol acts through mitogen-activated protein kinases and protein kinase B/AKT to elicit protection in a model of neuroinflammation in BV2 microglial cells. British Journal of Pharmacology 2011;164(3):1008-25.
29. 29. Yeon MJ, et al. Anti-inflammatory effects of Kaempferol on Helicobacter pylori-induced inflammation. Bioscience, Biotechnology, and Biochemistry 2019;83(1):166-173.