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Apigenin'in potansiyel farmakolojik etkileri üzerine bir derleme

Year 2023, Volume: 32 Issue: 2, 113 - 119, 30.06.2023
https://doi.org/10.17827/aktd.1267942

Abstract

Apigenin, günlük hayatta tükettiğimiz meyve ve sebzelerde bolca bulunan, çeşitli sağlık sorunlarının önlenmesinde ve tedavisinde önemli bir rol oynayan flavonoidlerden biridir. Apigeninin, başlıca anti-oksidan, anti-inflamatuvar ve anti-neoplastik olmak üzere çeşitli farmokolojik etkileri bulunmakla birlikte, bu etkilerini spesifik yolaklardaki proteinleri up ya da down regüle ederek sergilemektedir. Bu çalışmada apigeninin özellikle inflamasyon, oksidan-antioksidan denge, kanser, apoptozis ve hücre döngüsü üzerine etkilerine odaklanılmış ve bu özellikleri in vivo ve in vitro çalışmalarla desteklenmiştir. Yapılan araştırmalar neticesinde apigeninin anti-inflamatuvar, anti-oksidan ve anti-kanserojen özellikler sergilediği neticesine varılmıştır. Bununla birlikte apigeninin hasar görmüş, yıpranmış ya da kanseröz hale dönüşmüş hücreleri apoptozise yönlendirdiği, hücre döngüsünü çeşitli kontrol noktalarında durdurarak bu tür hücrelerin çoğalmasını engellediği ve bu şekilde antiproliferatif etki sergilediği gözlenmiştir.

References

  • Kaynaklar 1. Vazhappilly CG, Amararathna M, Cyril AC, Linger R, Matar R, Merheb M, et al. Current methodologies to refine bioavailability, delivery, and therapeutic efficacy of plant flavonoids in cancer treatment. The Journal of Nutritional Biochemistry. 2021;94:108623.
  • 2. Harborne JB, Williams CA. Advances in flavonoid research since 1992. Phytochemistry. 2000;55(6):481-504.
  • 3. An P, AD D, SR C. Flavonoids: an overview. Journal of nutritional science. 2016;5:e47.
  • 4. Dwivedi S, Malik C, Chhokar V. Molecular structure, biological functions, and metabolic regulation of flavonoids. Plant Biotechnology: Recent Advancements and Developments. 2017:171-88.
  • 5. Rodríguez-García C, Sánchez-Quesada C, Gaforio JJ. Dietary flavonoids as cancer chemopreventive agents: An updated review of human studies. Antioxidants. 2019;8(5):137.
  • 6. Balasundram N, Sundram K, Samman S. Phenolic compounds in plants and agri-industrial by-products: Antioxidant activity, occurrence, and potential uses. Food chemistry. 2006;99(1):191-203.
  • 7. Falcone Ferreyra ML, Rius SP, Casati P. Flavonoids: biosynthesis, biological functions, and biotechnological applications. Frontiers in plant science. 2012;3:222.
  • 8. Nabavi SF, Khan H, D'onofrio G, Šamec D, Shirooie S, Dehpour AR, et al. Apigenin as neuroprotective agent: Of mice and men. Pharmacological Research. 2018;128:359-65.
  • 9. Nurgali K, Jagoe RT, Abalo R. Adverse effects of cancer chemotherapy: Anything new to improve tolerance and reduce sequelae? : Frontiers Media SA; 2018. p. 245.
  • 10. Zhang J, Liu D, Huang Y, Gao Y, Qian S. Biopharmaceutics classification and intestinal absorption study of apigenin. International journal of pharmaceutics. 2012;436(1-2):311-7.
  • 11. Shukla S, Gupta S. Apigenin: a promising molecule for cancer prevention. Pharmaceutical research. 2010;27:962-78.
  • 12. Ekor M. The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Frontiers in pharmacology. 2014;4:177.
  • 13. Ghorbani A. Mechanisms of antidiabetic effects of flavonoid rutin. Biomedicine & Pharmacotherapy. 2017;96:305-12.
  • 14. Kopustinskiene DM, Jakstas V, Savickas A, Bernatoniene J. Flavonoids as anticancer agents. Nutrients. 2020;12(2):457.
  • 15. Maleki SJ, Crespo JF, Cabanillas B. Anti-inflammatory effects of flavonoids. Food chemistry. 2019;299:125124.
  • 16. Gutierrez-Merino C, Lopez-Sanchez C, Lagoa R, K Samhan-Arias A, Bueno C, Garcia-Martinez V. Neuroprotective actions of flavonoids. Current medicinal chemistry. 2011;18(8):1195-212.
  • 17. Mahmoud AM, Hernandez Bautista RJ, Sandhu MA, Hussein OE. Beneficial effects of citrus flavonoids on cardiovascular and metabolic health. Oxidative medicine and cellular longevity. 2019;2019.
  • 18. Vazhappilly CG, Ansari SA, Al-Jaleeli R, Al-Azawi AM, Ramadan WS, Menon V, et al. Role of flavonoids in thrombotic, cardiovascular, and inflammatory diseases. Inflammopharmacology. 2019;27:863-9.
  • 19. Heim KE, Tagliaferro AR, Bobilya DJ. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. The Journal of nutritional biochemistry. 2002;13(10):572-84.
  • 20. Sarian MN, Ahmed QU, Mat So’ad SZ, Alhassan AM, Murugesu S, Perumal V, et al. Antioxidant and antidiabetic effects of flavonoids: A structure-activity relationship based study. BioMed research international. 2017;2017.
  • 21. Ali F, Rahul, Naz F, Jyoti S, Siddique YH. Health functionality of apigenin: A review. International Journal of Food Properties. 2017;20(6):1197-238.
  • 22. Wen W, Li D, Li X, Gao Y, Li W, Li H, et al. Metabolome-based genome-wide association study of maize kernel leads to novel biochemical insights. Nature communications. 2014;5(1):3438.
  • 23. Sung B, Chung HY, Kim ND. Role of apigenin in cancer prevention via the induction of apoptosis and autophagy. Journal of cancer prevention. 2016;21(4):216.
  • 24. Kim HP, Son KH, Chang HW, Kang SS. Anti-inflammatory plant flavonoids and cellular action mechanisms. Journal of pharmacological sciences. 2004;96(3):229-45.
  • 25. Zhang X-J, Shu L, Jun-Peng X, Zhi-Qiang L, Feng-Rui S. Effect of type 2 diabetes mellitus on flavonoid pharmacokinetics and tissue distribution after oral administration of Radix Scutellaria extract in rats. Chinese journal of natural medicines. 2018;16(6):418-27.
  • 26. Hussein MM, Althagafi HA, Alharthi F, Albrakati A, Alsharif KF, Theyab A, et al. Apigenin attenuates molecular, biochemical, and histopathological changes associated with renal impairments induced by gentamicin exposure in rats. Environmental Science and Pollution Research. 2022;29(43):65276-88.
  • 27. Al-Khayri JM, Sahana GR, Nagella P, Joseph BV, Alessa FM, Al-Mssallem MQ. Flavonoids as potential anti-inflammatory molecules: A review. Molecules. 2022;27(9):2901.
  • 28. Cambay Z, Ilhan N, Susam S, Muz MH. BMI and adipocytokine changes in COPD exacerbation and stable COPD. Indian Journal of Biochemistry and Biophysics (IJBB). 2021;58(5):472-7.
  • 29. Poljsak B, Šuput D, Milisav I. Achieving the balance between ROS and antioxidants: when to use the synthetic antioxidants. Oxidative medicine and cellular longevity. 2013;2013.
  • 30. Chagas MdSS, Behrens MD, Moragas-Tellis CJ, Penedo GX, Silva AR, Gonçalves-de-Albuquerque CF. Flavonols and Flavones as Potential anti-Inflammatory, Antioxidant, and Antibacterial Compounds. Oxidative Medicine and Cellular Longevity. 2022;2022.
  • 31. Hodaei M, Rahimmalek M, Arzani A, Talebi M. The effect of water stress on phytochemical accumulation, bioactive compounds and expression of key genes involved in flavonoid biosynthesis in Chrysanthemum morifolium L. Industrial Crops and Products. 2018;120:295-304.
  • 32. Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. Journal of nutritional science. 2016;5:e47.
  • 33. Peng F, Hu Y, Peng S, Zeng N, Shi L. Apigenin exerts protective effect and restores ovarian function in dehydroepiandrosterone induced polycystic ovary syndrome rats: A biochemical and histological analysis. Annals of Medicine. 2022;54(1):578-87.
  • 34. Fehaid A, Al‐Ghamdi MS, Alzahrani KJ, Theyab A, Al‐Amer OM, Al‐Shehri SS, et al. Apigenin protects from hepatorenal damage caused by lead acetate in rats. Journal of Biochemical and Molecular Toxicology. 2022:e23275.
  • 35. Kim M, Jung J, Jeong NY, Chung H-J. The natural plant flavonoid apigenin is a strong antioxidant that effectively delays peripheral neurodegenerative processes. Anatomical Science International. 2019;94(4):285-94.
  • 36. Tatar O, Ilhan N, Ilhan N, Susam S, Ozercan IH. Is there any potential anticancer effect of raloxifene and fluoxetine on DMBA‐induced rat breast cancer? Journal of Biochemical and Molecular Toxicology. 2019;33(9):e22371.
  • 37. Yan X, Qi M, Li P, Zhan Y, Shao H. Apigenin in cancer therapy: Anti-cancer effects and mechanisms of action. Cell & bioscience. 2017;7(1):1-16.
  • 38. Birt DF, Walker B, Tibbels MG, Bresnick E. Anti-mutagenesis and anti-promotion by apigenin, robinetin and indole-3-carbinol. Carcinogenesis. 1986;7(6):959-63.
  • 39. Chen Y-H, Wu J-X, Yang S-F, Yang C-K, Chen T-H, Hsiao Y-H. Anticancer Effects and Molecular Mechanisms of Apigenin in Cervical Cancer Cells. Cancers. 2022;14(7):1824.
  • 40. Wang M, Firrman J, Liu L, Yam K. A review on flavonoid apigenin: Dietary intake, ADME, antimicrobial effects, and interactions with human gut microbiota. BioMed research international. 2019;2019.
  • 41. Domingo-Domenech J, Mellado B, Ferrer B, Truan D, Codony-Servat J, Sauleda S, et al. Activation of nuclear factor-κB in human prostate carcinogenesis and association to biochemical relapse. British journal of cancer. 2005;93(11):1285-94.
  • 42. Pfeffer CM, Singh AT. Apoptosis: a target for anticancer therapy. International journal of molecular sciences. 2018;19(2):448.
  • 43. Maeda Y, Takahashi H, Nakai N, Yanagita T, Ando N, Okubo T, et al. Apigenin induces apoptosis by suppressing Bcl-xl and Mcl-1 simultaneously via signal transducer and activator of transcription 3 signaling in colon cancer. International journal of oncology. 2018;52(5):1661-73.
  • 44. Woo JS, Choo GS, Yoo ES, Kim SH, Lee JH, Han SH, et al. Apigenin induces apoptosis by regulating Akt and MAPK pathways in human melanoma cell A375SM. Molecular Medicine Reports. 2020;22(6):4877-89.
  • 45. Vrhovac Madunić I, Madunić J, Antunović M, Paradžik M, Garaj-Vrhovac V, Breljak D, et al. Apigenin, a dietary flavonoid, induces apoptosis, DNA damage, and oxidative stress in human breast cancer MCF-7 and MDA MB-231 cells. Naunyn-Schmiedeberg's archives of pharmacology. 2018;391:537-50.
  • 46. Ali S, Dar MI, Rather RA, Afroze D. Cell Cycle and Factors Involved in Inhibition or Progression of Breast Cancer. Breast Cancer Biology: IntechOpen; 2020.
  • 47. Ujiki MB, Ding X-Z, Salabat MR, Bentrem DJ, Golkar L, Milam B, et al. Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle arrest. Molecular cancer. 2006;5:1-8.
  • 48. Maggioni D, Garavello W, Rigolio R, Pignataro L, Gaini R, Nicolini G. Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis. International Journal of Oncology. 2013;43(5):1675-82.
Year 2023, Volume: 32 Issue: 2, 113 - 119, 30.06.2023
https://doi.org/10.17827/aktd.1267942

Abstract

References

  • Kaynaklar 1. Vazhappilly CG, Amararathna M, Cyril AC, Linger R, Matar R, Merheb M, et al. Current methodologies to refine bioavailability, delivery, and therapeutic efficacy of plant flavonoids in cancer treatment. The Journal of Nutritional Biochemistry. 2021;94:108623.
  • 2. Harborne JB, Williams CA. Advances in flavonoid research since 1992. Phytochemistry. 2000;55(6):481-504.
  • 3. An P, AD D, SR C. Flavonoids: an overview. Journal of nutritional science. 2016;5:e47.
  • 4. Dwivedi S, Malik C, Chhokar V. Molecular structure, biological functions, and metabolic regulation of flavonoids. Plant Biotechnology: Recent Advancements and Developments. 2017:171-88.
  • 5. Rodríguez-García C, Sánchez-Quesada C, Gaforio JJ. Dietary flavonoids as cancer chemopreventive agents: An updated review of human studies. Antioxidants. 2019;8(5):137.
  • 6. Balasundram N, Sundram K, Samman S. Phenolic compounds in plants and agri-industrial by-products: Antioxidant activity, occurrence, and potential uses. Food chemistry. 2006;99(1):191-203.
  • 7. Falcone Ferreyra ML, Rius SP, Casati P. Flavonoids: biosynthesis, biological functions, and biotechnological applications. Frontiers in plant science. 2012;3:222.
  • 8. Nabavi SF, Khan H, D'onofrio G, Šamec D, Shirooie S, Dehpour AR, et al. Apigenin as neuroprotective agent: Of mice and men. Pharmacological Research. 2018;128:359-65.
  • 9. Nurgali K, Jagoe RT, Abalo R. Adverse effects of cancer chemotherapy: Anything new to improve tolerance and reduce sequelae? : Frontiers Media SA; 2018. p. 245.
  • 10. Zhang J, Liu D, Huang Y, Gao Y, Qian S. Biopharmaceutics classification and intestinal absorption study of apigenin. International journal of pharmaceutics. 2012;436(1-2):311-7.
  • 11. Shukla S, Gupta S. Apigenin: a promising molecule for cancer prevention. Pharmaceutical research. 2010;27:962-78.
  • 12. Ekor M. The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Frontiers in pharmacology. 2014;4:177.
  • 13. Ghorbani A. Mechanisms of antidiabetic effects of flavonoid rutin. Biomedicine & Pharmacotherapy. 2017;96:305-12.
  • 14. Kopustinskiene DM, Jakstas V, Savickas A, Bernatoniene J. Flavonoids as anticancer agents. Nutrients. 2020;12(2):457.
  • 15. Maleki SJ, Crespo JF, Cabanillas B. Anti-inflammatory effects of flavonoids. Food chemistry. 2019;299:125124.
  • 16. Gutierrez-Merino C, Lopez-Sanchez C, Lagoa R, K Samhan-Arias A, Bueno C, Garcia-Martinez V. Neuroprotective actions of flavonoids. Current medicinal chemistry. 2011;18(8):1195-212.
  • 17. Mahmoud AM, Hernandez Bautista RJ, Sandhu MA, Hussein OE. Beneficial effects of citrus flavonoids on cardiovascular and metabolic health. Oxidative medicine and cellular longevity. 2019;2019.
  • 18. Vazhappilly CG, Ansari SA, Al-Jaleeli R, Al-Azawi AM, Ramadan WS, Menon V, et al. Role of flavonoids in thrombotic, cardiovascular, and inflammatory diseases. Inflammopharmacology. 2019;27:863-9.
  • 19. Heim KE, Tagliaferro AR, Bobilya DJ. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. The Journal of nutritional biochemistry. 2002;13(10):572-84.
  • 20. Sarian MN, Ahmed QU, Mat So’ad SZ, Alhassan AM, Murugesu S, Perumal V, et al. Antioxidant and antidiabetic effects of flavonoids: A structure-activity relationship based study. BioMed research international. 2017;2017.
  • 21. Ali F, Rahul, Naz F, Jyoti S, Siddique YH. Health functionality of apigenin: A review. International Journal of Food Properties. 2017;20(6):1197-238.
  • 22. Wen W, Li D, Li X, Gao Y, Li W, Li H, et al. Metabolome-based genome-wide association study of maize kernel leads to novel biochemical insights. Nature communications. 2014;5(1):3438.
  • 23. Sung B, Chung HY, Kim ND. Role of apigenin in cancer prevention via the induction of apoptosis and autophagy. Journal of cancer prevention. 2016;21(4):216.
  • 24. Kim HP, Son KH, Chang HW, Kang SS. Anti-inflammatory plant flavonoids and cellular action mechanisms. Journal of pharmacological sciences. 2004;96(3):229-45.
  • 25. Zhang X-J, Shu L, Jun-Peng X, Zhi-Qiang L, Feng-Rui S. Effect of type 2 diabetes mellitus on flavonoid pharmacokinetics and tissue distribution after oral administration of Radix Scutellaria extract in rats. Chinese journal of natural medicines. 2018;16(6):418-27.
  • 26. Hussein MM, Althagafi HA, Alharthi F, Albrakati A, Alsharif KF, Theyab A, et al. Apigenin attenuates molecular, biochemical, and histopathological changes associated with renal impairments induced by gentamicin exposure in rats. Environmental Science and Pollution Research. 2022;29(43):65276-88.
  • 27. Al-Khayri JM, Sahana GR, Nagella P, Joseph BV, Alessa FM, Al-Mssallem MQ. Flavonoids as potential anti-inflammatory molecules: A review. Molecules. 2022;27(9):2901.
  • 28. Cambay Z, Ilhan N, Susam S, Muz MH. BMI and adipocytokine changes in COPD exacerbation and stable COPD. Indian Journal of Biochemistry and Biophysics (IJBB). 2021;58(5):472-7.
  • 29. Poljsak B, Šuput D, Milisav I. Achieving the balance between ROS and antioxidants: when to use the synthetic antioxidants. Oxidative medicine and cellular longevity. 2013;2013.
  • 30. Chagas MdSS, Behrens MD, Moragas-Tellis CJ, Penedo GX, Silva AR, Gonçalves-de-Albuquerque CF. Flavonols and Flavones as Potential anti-Inflammatory, Antioxidant, and Antibacterial Compounds. Oxidative Medicine and Cellular Longevity. 2022;2022.
  • 31. Hodaei M, Rahimmalek M, Arzani A, Talebi M. The effect of water stress on phytochemical accumulation, bioactive compounds and expression of key genes involved in flavonoid biosynthesis in Chrysanthemum morifolium L. Industrial Crops and Products. 2018;120:295-304.
  • 32. Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. Journal of nutritional science. 2016;5:e47.
  • 33. Peng F, Hu Y, Peng S, Zeng N, Shi L. Apigenin exerts protective effect and restores ovarian function in dehydroepiandrosterone induced polycystic ovary syndrome rats: A biochemical and histological analysis. Annals of Medicine. 2022;54(1):578-87.
  • 34. Fehaid A, Al‐Ghamdi MS, Alzahrani KJ, Theyab A, Al‐Amer OM, Al‐Shehri SS, et al. Apigenin protects from hepatorenal damage caused by lead acetate in rats. Journal of Biochemical and Molecular Toxicology. 2022:e23275.
  • 35. Kim M, Jung J, Jeong NY, Chung H-J. The natural plant flavonoid apigenin is a strong antioxidant that effectively delays peripheral neurodegenerative processes. Anatomical Science International. 2019;94(4):285-94.
  • 36. Tatar O, Ilhan N, Ilhan N, Susam S, Ozercan IH. Is there any potential anticancer effect of raloxifene and fluoxetine on DMBA‐induced rat breast cancer? Journal of Biochemical and Molecular Toxicology. 2019;33(9):e22371.
  • 37. Yan X, Qi M, Li P, Zhan Y, Shao H. Apigenin in cancer therapy: Anti-cancer effects and mechanisms of action. Cell & bioscience. 2017;7(1):1-16.
  • 38. Birt DF, Walker B, Tibbels MG, Bresnick E. Anti-mutagenesis and anti-promotion by apigenin, robinetin and indole-3-carbinol. Carcinogenesis. 1986;7(6):959-63.
  • 39. Chen Y-H, Wu J-X, Yang S-F, Yang C-K, Chen T-H, Hsiao Y-H. Anticancer Effects and Molecular Mechanisms of Apigenin in Cervical Cancer Cells. Cancers. 2022;14(7):1824.
  • 40. Wang M, Firrman J, Liu L, Yam K. A review on flavonoid apigenin: Dietary intake, ADME, antimicrobial effects, and interactions with human gut microbiota. BioMed research international. 2019;2019.
  • 41. Domingo-Domenech J, Mellado B, Ferrer B, Truan D, Codony-Servat J, Sauleda S, et al. Activation of nuclear factor-κB in human prostate carcinogenesis and association to biochemical relapse. British journal of cancer. 2005;93(11):1285-94.
  • 42. Pfeffer CM, Singh AT. Apoptosis: a target for anticancer therapy. International journal of molecular sciences. 2018;19(2):448.
  • 43. Maeda Y, Takahashi H, Nakai N, Yanagita T, Ando N, Okubo T, et al. Apigenin induces apoptosis by suppressing Bcl-xl and Mcl-1 simultaneously via signal transducer and activator of transcription 3 signaling in colon cancer. International journal of oncology. 2018;52(5):1661-73.
  • 44. Woo JS, Choo GS, Yoo ES, Kim SH, Lee JH, Han SH, et al. Apigenin induces apoptosis by regulating Akt and MAPK pathways in human melanoma cell A375SM. Molecular Medicine Reports. 2020;22(6):4877-89.
  • 45. Vrhovac Madunić I, Madunić J, Antunović M, Paradžik M, Garaj-Vrhovac V, Breljak D, et al. Apigenin, a dietary flavonoid, induces apoptosis, DNA damage, and oxidative stress in human breast cancer MCF-7 and MDA MB-231 cells. Naunyn-Schmiedeberg's archives of pharmacology. 2018;391:537-50.
  • 46. Ali S, Dar MI, Rather RA, Afroze D. Cell Cycle and Factors Involved in Inhibition or Progression of Breast Cancer. Breast Cancer Biology: IntechOpen; 2020.
  • 47. Ujiki MB, Ding X-Z, Salabat MR, Bentrem DJ, Golkar L, Milam B, et al. Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle arrest. Molecular cancer. 2006;5:1-8.
  • 48. Maggioni D, Garavello W, Rigolio R, Pignataro L, Gaini R, Nicolini G. Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis. International Journal of Oncology. 2013;43(5):1675-82.
There are 48 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Review
Authors

Solmaz Susam 0000-0002-7503-2416

Gürkan Çıkım 0000-0002-7572-3962

Early Pub Date June 23, 2023
Publication Date June 30, 2023
Acceptance Date June 6, 2023
Published in Issue Year 2023 Volume: 32 Issue: 2

Cite

AMA Susam S, Çıkım G. Apigenin’in potansiyel farmakolojik etkileri üzerine bir derleme. aktd. June 2023;32(2):113-119. doi:10.17827/aktd.1267942