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Hispidulinin Sağlıklı Hücre Hatlarında Sitotoksik, Apoptotik ve Nekrotik Etkilerinin Değerlendirilmesi

Year 2023, , 193 - 198, 01.07.2023
https://doi.org/10.34248/bsengineering.1240663

Abstract

Hispidulin çeşitli farmakolojik özelliklere sahip olmasından dolayı uzun süredir kanser araştırmalarında kullanılmaktadır ancak bu maddenin sağlıklı hücrelerde sitotoksik etkisiyle ilgili sınırlı sayıda çalışma bulunmaktadır. Bu çalışmada ilk defa, hispidulin geniş doz aralığında (0-800 μM) sağlıklı hücre hatları ile denendi ve kulanımının güvenliği MTT ve Akım sitometrisi analizleriyle değerlendirildi. Bu amaçla, İnsan akciğer fibroblastı (MRC-5), Sıçan Primer Akciğer Fibroblastı (RA-6013) ve Sıçan Primer Trakeal Fibroblastı (RA-6217) hücreleri 48 saat boyunca hispidulinle muamele edildi. Hispidulin, düşük dozlarda hücre canlılığı üzerinde önemli etkiler göstermedi ancak özellikle 400 ve 800 μM dozlarında hücrelerin canlılığında istatistiksel anlamda ciddi bir azalmaya neden oldu. Hispidulinin IC50 değeri, MRC-5 hücreleri için 563.63 µM, RA-6013 hücrelerinde 194.30 µM ve RA-6217 hücrelerinde ise 311.98 µM olarak belirlendi. Ayrıca 800 μM hispidulin, tüm sağlıklı hücreler üzerinde güçlü apoptotik ve nekrotik etki gösterdi. Sonuçlarımız, hispidulinin düşük dozlarda (0-200 μM) sağlıklı hücrelerde antisitotoksik nitelikte olduğunu ve gelecekteki kanser ve solunum yolu hastalıkları tedavisi için güvenilir doğal bir bileşik olma potansiyeline sahip olduğunu göstermektedir.

Thanks

Sağladığı imkanlardan dolayı DAYTAM (Doğu Anadolu Yüksek Teknoloji Araştırma ve Uygulama Merkezi)’a teşekkür ederim.

References

  • An P, Wu T, Yu H, Fang K, Ren Z, Tang M. 2018. Hispidulin protects against focal cerebral ischemia reperfusion injury in rats. J Mol Neurosci, 65(2): 203-212.
  • Ashaq, A., Maqbool, M. F., Maryam, A., Khan, M., Shakir, H. A., Irfan, M., Qazi JI, Li Y, Ma, T. 2021. Hispidulin: A novel natural compound with therapeutic potential against human cancers. Phytother Res, 35(2): 771-789.
  • Cong Y, Wu S, Han J, Chen J, Liu H, Sun Q, Wu Y, Fang, Y. (2016). Pharmacokinetics of homoplantaginin in rats following intravenous, peritoneal injection and oral administration. J Pharm Biomed Anal, 129: 405-409.
  • Dai, Y., Sun, X., Li, B., Ma, H., Wu, P., Zhang, Y., Zhu M, Li HM, Qin M., Wu, C.Z. 2021. The Effect of Hispidulin, a Flavonoid from Salvia plebeia, on Human Nasopharyngeal Carcinoma CNE-2Z Cell Proliferation, Migration, Invasion, and Apoptosis. Molecules, 26(6): 1604.
  • Gao H, Jiang Q, Han Y, Peng J, Wang C. 2015. Hispidulin potentiates the antitumor effect of sunitinib against human renal cell carcinoma in laboratory models. Cell Biochem Biophys, 71(2): 757-764.
  • Han M, Gao H, Ju P, Gao MQ, Yuan YP, Chen XH, Liu K, Han Y, Han, ZW. 2018. Hispidulin inhibits hepatocellular carcinoma growth and metastasis through AMPK and ERK signaling mediated activation of PPARγ. Biomed Pharmacother, 103: 272-283.
  • Huang L, Huang K, Ning H. 2018. Hispidulin prevents sevoflurane—Induced memory dysfunction in aged rats. Biomed Pharmacother, 97: 412-422.
  • Kaufman PB, Csake LJ, Warber S, Duke JA, Brielmann HL. 1998. Natural products from plants, CRC Press, Boca Raton.
  • Kavakcıoğlu Yardımcı B, Geyikoglu F, Aysin F, Koc K, Simsek Ozek N, Küçükatay V. 2021. The cytotoxic and apoptotic effects of beta-blockers with different selectivity on cancerous and healthy lung cell lines. Mol Biol Rep 48(5): 4009-4019.
  • Kim HA, Lee J. 2021. Hispidulin modulates epithelial mesenchymal transition in breast cancer cells. Oncol. Lett, 21(2): 1-1.
  • Lin FJ, Yen FL, Chen PC, Wang MC, Lin CN, Lee CW, Ko HH. 2014. HPLC-fingerprints and antioxidant constituents of Phyla nodiflora, Sci. World J. 2014.
  • Lin SR, Fu YS, Tsai MJ, Cheg H, Weng CF. 2017. Natural compounds from herbs that can pottentially execute as autophagy inducers for cancer therapy. Int J Mol Sci, 18:1412.
  • Lin TY, Lu CW, Wang CC, Lu JF, Wang SJ. 2012. Hispidulin inhibits the release of glutamate in rat cerebrocortical nerve terminals. Toxicol Appl Pharmacol, 263(2): 233-243.
  • Liu K, Zhao F, Yan J, Xia Z, Jiang D, Ma P. 2020. Hispidulin: A promising flavonoid with diverse anti-cancer properties. Life Sci, 259: 118395.
  • Lv L, Zhang W, Li T, Jiang L, Lu X, Lin J. 2020. Hispidulin exhibits potent anticancer activity in vitro and in vivo through activating ER stress in non small cell lung cancer cells. Oncol Reports, 43(6): 1995-2003.
  • Mocan A, Vodnar DC, Vlase L, Crișan O, Gheldiu AM, Crișan G. 2015. Phytochemical characterization of Veronica officinalis L., V. teucrium L. and V. orchidea Crantz from Romania and their antioxidant and antimicrobial properties. Int J Mol Sci, 16(9): 21109-21127.
  • Patel, K., Patel, DK. 2017. Medicinal importance, pharmacological activities, and analytical aspects of hispidulin: A concise report. J Tradit Complement Med, 7(3): 360-366.
  • Thitilertdecha P, Tantithavorn V, Poungpairoj P, Onlamoon N. 2019. Determination of suppressive effect on human T-cell activation by hispidulin, nepetin, and vanillic acid. Immunopharmacol Immunotoxicol 41(6): 591-598.
  • Thitilertdecha P, Tantithavorn, V, Poungpairoj P, Onlamoon N. 2022. Synergistic immunosuppressive effect of hispidulin and nepetin mixtures on human T lymphocytes. Immunopharmacol Immunotoxicol, 44(5): 693-703.
  • Wang Y, Guo S, Jia Y, Yu X, Mou R, Li X. 2021. Hispidulin inhibits proliferation, migration, and invasion by promoting autophagy via regulation of PPARγ activation in prostate cancer cells and xenograft models. Biosci Biotechnol Biochem, 85(4): 786-797.
  • Wilcox EC, Edelman ER. 2022. Substratum interactions modulate interplay between endothelial cell, epithelial cell, and fibroblast phenotype and immunomodulatory function. Biomaterials, 289: 121785.
  • Yu CY, Su KY, Lee PL, Jhan JY, Tsao PH, Chan DC, Chen YLS. 2013. Potential therapeutic role of hispidulin in gastric cancer through induction of apoptosis via NAG-1 signaling. Evid Based Complementary Altern Med, 2013.

Evaluation of Cytotoxic, Apoptotic, and Necrotic Efficiency of Hispidulin in Healthy Cell Lines

Year 2023, , 193 - 198, 01.07.2023
https://doi.org/10.34248/bsengineering.1240663

Abstract

Since hispidulin has various pharmacological properties, its use in cancer research has been increasing for a long time, but there are very limited studies on its cytotoxic effect in healthy cells. In this study, for the first time, the safety of hispidulin in a wide dose range (0-800 μM) was evaluated on healthy cell lines by MTT and Flow cytometry assays. For this purpose, Human lung fibroblast (MRC-5), Rat Primary Lung Fibroblast (RA-6013), and Rat Primary Tracheal Fibroblast (RA-6217) cells were treated with hispidulin for 48 hours. Hispidulin did not show significant effects on cell viability at low doses; however, caused a statistically significant reduction in cell viability, especially at doses of 400 and 800 μM. The IC50 value of hispidulin was determined as 563.63 µM for MRC-5 cells, 194.30 µM for RA-6013 cells, and 311.98 µM for RA-6217 cells. Moreover, 800 μM hispidulin showed a strong apoptotic and necrotic effect on all healthy cells. Our results show that hispidulin is anticytotoxic in healthy cells at low doses (0-200 μM) and has the potential to be a safe natural compound for future treatment of cancer and respiratory diseases.

References

  • An P, Wu T, Yu H, Fang K, Ren Z, Tang M. 2018. Hispidulin protects against focal cerebral ischemia reperfusion injury in rats. J Mol Neurosci, 65(2): 203-212.
  • Ashaq, A., Maqbool, M. F., Maryam, A., Khan, M., Shakir, H. A., Irfan, M., Qazi JI, Li Y, Ma, T. 2021. Hispidulin: A novel natural compound with therapeutic potential against human cancers. Phytother Res, 35(2): 771-789.
  • Cong Y, Wu S, Han J, Chen J, Liu H, Sun Q, Wu Y, Fang, Y. (2016). Pharmacokinetics of homoplantaginin in rats following intravenous, peritoneal injection and oral administration. J Pharm Biomed Anal, 129: 405-409.
  • Dai, Y., Sun, X., Li, B., Ma, H., Wu, P., Zhang, Y., Zhu M, Li HM, Qin M., Wu, C.Z. 2021. The Effect of Hispidulin, a Flavonoid from Salvia plebeia, on Human Nasopharyngeal Carcinoma CNE-2Z Cell Proliferation, Migration, Invasion, and Apoptosis. Molecules, 26(6): 1604.
  • Gao H, Jiang Q, Han Y, Peng J, Wang C. 2015. Hispidulin potentiates the antitumor effect of sunitinib against human renal cell carcinoma in laboratory models. Cell Biochem Biophys, 71(2): 757-764.
  • Han M, Gao H, Ju P, Gao MQ, Yuan YP, Chen XH, Liu K, Han Y, Han, ZW. 2018. Hispidulin inhibits hepatocellular carcinoma growth and metastasis through AMPK and ERK signaling mediated activation of PPARγ. Biomed Pharmacother, 103: 272-283.
  • Huang L, Huang K, Ning H. 2018. Hispidulin prevents sevoflurane—Induced memory dysfunction in aged rats. Biomed Pharmacother, 97: 412-422.
  • Kaufman PB, Csake LJ, Warber S, Duke JA, Brielmann HL. 1998. Natural products from plants, CRC Press, Boca Raton.
  • Kavakcıoğlu Yardımcı B, Geyikoglu F, Aysin F, Koc K, Simsek Ozek N, Küçükatay V. 2021. The cytotoxic and apoptotic effects of beta-blockers with different selectivity on cancerous and healthy lung cell lines. Mol Biol Rep 48(5): 4009-4019.
  • Kim HA, Lee J. 2021. Hispidulin modulates epithelial mesenchymal transition in breast cancer cells. Oncol. Lett, 21(2): 1-1.
  • Lin FJ, Yen FL, Chen PC, Wang MC, Lin CN, Lee CW, Ko HH. 2014. HPLC-fingerprints and antioxidant constituents of Phyla nodiflora, Sci. World J. 2014.
  • Lin SR, Fu YS, Tsai MJ, Cheg H, Weng CF. 2017. Natural compounds from herbs that can pottentially execute as autophagy inducers for cancer therapy. Int J Mol Sci, 18:1412.
  • Lin TY, Lu CW, Wang CC, Lu JF, Wang SJ. 2012. Hispidulin inhibits the release of glutamate in rat cerebrocortical nerve terminals. Toxicol Appl Pharmacol, 263(2): 233-243.
  • Liu K, Zhao F, Yan J, Xia Z, Jiang D, Ma P. 2020. Hispidulin: A promising flavonoid with diverse anti-cancer properties. Life Sci, 259: 118395.
  • Lv L, Zhang W, Li T, Jiang L, Lu X, Lin J. 2020. Hispidulin exhibits potent anticancer activity in vitro and in vivo through activating ER stress in non small cell lung cancer cells. Oncol Reports, 43(6): 1995-2003.
  • Mocan A, Vodnar DC, Vlase L, Crișan O, Gheldiu AM, Crișan G. 2015. Phytochemical characterization of Veronica officinalis L., V. teucrium L. and V. orchidea Crantz from Romania and their antioxidant and antimicrobial properties. Int J Mol Sci, 16(9): 21109-21127.
  • Patel, K., Patel, DK. 2017. Medicinal importance, pharmacological activities, and analytical aspects of hispidulin: A concise report. J Tradit Complement Med, 7(3): 360-366.
  • Thitilertdecha P, Tantithavorn V, Poungpairoj P, Onlamoon N. 2019. Determination of suppressive effect on human T-cell activation by hispidulin, nepetin, and vanillic acid. Immunopharmacol Immunotoxicol 41(6): 591-598.
  • Thitilertdecha P, Tantithavorn, V, Poungpairoj P, Onlamoon N. 2022. Synergistic immunosuppressive effect of hispidulin and nepetin mixtures on human T lymphocytes. Immunopharmacol Immunotoxicol, 44(5): 693-703.
  • Wang Y, Guo S, Jia Y, Yu X, Mou R, Li X. 2021. Hispidulin inhibits proliferation, migration, and invasion by promoting autophagy via regulation of PPARγ activation in prostate cancer cells and xenograft models. Biosci Biotechnol Biochem, 85(4): 786-797.
  • Wilcox EC, Edelman ER. 2022. Substratum interactions modulate interplay between endothelial cell, epithelial cell, and fibroblast phenotype and immunomodulatory function. Biomaterials, 289: 121785.
  • Yu CY, Su KY, Lee PL, Jhan JY, Tsao PH, Chan DC, Chen YLS. 2013. Potential therapeutic role of hispidulin in gastric cancer through induction of apoptosis via NAG-1 signaling. Evid Based Complementary Altern Med, 2013.
There are 22 citations in total.

Details

Primary Language Turkish
Subjects Engineering
Journal Section Research Articles
Authors

Ferhunde Aysin 0000-0003-1971-8031

Early Pub Date June 13, 2023
Publication Date July 1, 2023
Submission Date January 23, 2023
Acceptance Date April 29, 2023
Published in Issue Year 2023

Cite

APA Aysin, F. (2023). Hispidulinin Sağlıklı Hücre Hatlarında Sitotoksik, Apoptotik ve Nekrotik Etkilerinin Değerlendirilmesi. Black Sea Journal of Engineering and Science, 6(3), 193-198. https://doi.org/10.34248/bsengineering.1240663
AMA Aysin F. Hispidulinin Sağlıklı Hücre Hatlarında Sitotoksik, Apoptotik ve Nekrotik Etkilerinin Değerlendirilmesi. BSJ Eng. Sci. July 2023;6(3):193-198. doi:10.34248/bsengineering.1240663
Chicago Aysin, Ferhunde. “Hispidulinin Sağlıklı Hücre Hatlarında Sitotoksik, Apoptotik Ve Nekrotik Etkilerinin Değerlendirilmesi”. Black Sea Journal of Engineering and Science 6, no. 3 (July 2023): 193-98. https://doi.org/10.34248/bsengineering.1240663.
EndNote Aysin F (July 1, 2023) Hispidulinin Sağlıklı Hücre Hatlarında Sitotoksik, Apoptotik ve Nekrotik Etkilerinin Değerlendirilmesi. Black Sea Journal of Engineering and Science 6 3 193–198.
IEEE F. Aysin, “Hispidulinin Sağlıklı Hücre Hatlarında Sitotoksik, Apoptotik ve Nekrotik Etkilerinin Değerlendirilmesi”, BSJ Eng. Sci., vol. 6, no. 3, pp. 193–198, 2023, doi: 10.34248/bsengineering.1240663.
ISNAD Aysin, Ferhunde. “Hispidulinin Sağlıklı Hücre Hatlarında Sitotoksik, Apoptotik Ve Nekrotik Etkilerinin Değerlendirilmesi”. Black Sea Journal of Engineering and Science 6/3 (July 2023), 193-198. https://doi.org/10.34248/bsengineering.1240663.
JAMA Aysin F. Hispidulinin Sağlıklı Hücre Hatlarında Sitotoksik, Apoptotik ve Nekrotik Etkilerinin Değerlendirilmesi. BSJ Eng. Sci. 2023;6:193–198.
MLA Aysin, Ferhunde. “Hispidulinin Sağlıklı Hücre Hatlarında Sitotoksik, Apoptotik Ve Nekrotik Etkilerinin Değerlendirilmesi”. Black Sea Journal of Engineering and Science, vol. 6, no. 3, 2023, pp. 193-8, doi:10.34248/bsengineering.1240663.
Vancouver Aysin F. Hispidulinin Sağlıklı Hücre Hatlarında Sitotoksik, Apoptotik ve Nekrotik Etkilerinin Değerlendirilmesi. BSJ Eng. Sci. 2023;6(3):193-8.

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