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Hispidulin, metabolik disfonksiyonla ilişkili steatotik karaciğer hastalığı olan HepG2 hücre hattında lipid parametrelerini iyileştirebilir

Year 2024, Volume: 49 Issue: 4, 891 - 900, 30.12.2024
https://doi.org/10.17826/cumj.1520407

Abstract

Amaç: Metabolik ilişkili steatotik karaciğer hastalığı (MASLD) önemli bir sağlık sorunudur. Patogenezi hala net olmasa da insülin direnci, steatoz, inflamasyonun önemli yeri vardır. Tedavi için alternatif ajan çalışmaları devam etmektedir. Bu çalışma, bir flavonoid olan hispidulinin MASLD modelindeki etkisini inceleyen ilk çalışmadır.
Gereç ve Yöntem: MTT sitotoksisite testi ile hispidulin ve oleik asidin toksik olmayan konsantrasyonları belirlendi. Hücrelere önce hispidulin uygulandı, 2 saat sonra ise oleik asit verildi. Lipogenez için hücreler 24 saat inkübe edildi. Oil Red O boyama yöntemi kullanılarak hücre içi lipitler, hem nitel hem de nicel olarak gösterildi. Trigliserid ve Total kolesterol düzeyleri, Alanin aminotransferaz (ALT) ve aspartat aminotransferaz (AST) düzeyleri ve Adenozin monofosfat-aktif protein kinaz (AMPK) ve Sirtuin 1 (SIRT1) seviyeleri ölçüldü.
Bulgular: 40 µM Hispidulin grubunda model grubuna kıyasla; trigliserid seviyesini %67, total kolesterol seviyesini %53, ALT seviyesini %66, AST seviyesini %36 oranında anlamlı ölçüde azalttı. Ancak AMPK ve SIRT1 seviyelerinde artış görülmedi.
Sonuç: Hispidulinin MASLD' da hücresel lipid birikimini azaltıp, lipid parametrelerini iyileştirebileceği ve aminotransferaz enzim seviyelerini azaltabileceği belirlenmiştir. Fakat bu etkinin AMPK-SIRT1 yolu üzerinden değil de başka yolaklar üzerinden olabileceği düşünülmektedir. Hispidulinin MASLD' daki etki mekanizmalarını belirlemek için daha ileri araştırmalara ihtiyaç vardır.

Supporting Institution

This work was supported by Gaziantep University Scientific Research Projects

Project Number

TF.UT.21.44

References

  • Powell E, Wong V, Rinella M. Non-alcoholic fatty liver disease. Lancet. 2021;397:2212-24.
  • Rinella M, Lazarus J, Ratziu V, Francque S, Sanyal A, Kanwal Fea. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023;78:1966-86.
  • Byrne C, Targher G. NAFLD: a multisystem disease. J Hepatol. 2015;62:47-64.
  • Kuyumcu A, Pürnak T, Yıldız E. Non alkolik yağlı karaciğer hastalığı olan bireylerde fruktoz tüketiminin değerlendirilmesi. Turk J Clin Lab. 2019;10:190-6.
  • Rong L, Zou J, Ran W, Qi X, Chen Y, Cui Hea. Advancements in the treatment of non-alcoholic fatty liver disease (NAFLD). Front Endocrinol (Lausanne). 2022;13:1087260.
  • Harrison S, Bedossa P, Guy C, Schattenberg J, Loomba R, Taub Rea. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N Engl J Med. 2024;390:497-509.
  • Ray K. Resmetirom proves positive for NASH with liver fibrosis. Nat Rev Gastroenterol Hepatol. 2024;21:218.
  • Wang S, Sheng F, Zou L, Xiao J, Li P. Hyperoside attenuates non-alcoholic fatty liver disease in rats via cholesterol metabolism and bile acid metabolism. J Adv Res. 2021;34:109-22.
  • Ipsen D, Lykkesfeldt J, Tveden-Nyborg P. Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease. Cell Mol Life Sci. 2018;75:3313-27.
  • Athyros V, Alexandrides T, Bilianou H, Cholongitas E, Doumas M, Ganotakis Eea. The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An expert panel statement. Metabolism. 2017;71:17-32.
  • Ünal N, Yılmaz F, Akarca U, Nart D, Ersöz G, Karasu Zea. Nonalkolik yağlı karaciğer hastalığında histolojik progresyon ile klinik ve laboratuvar parametrelerin ilişkisi. The Turkish Journal of Academic Gastroenterology. 2020;19:63-74.
  • Anggreini P, Kuncoro, H, Sumiwi, SA, Levita, J. Role of the AMPK/SIRT1 pathway in non‑alcoholic fatty liver disease (Review). Mol Med Rep. 2023;27:35.
  • Smith B, Marcinko K, Desjardins E, Lally J, Ford R, Steinberg G. Treatment of nonalcoholic fatty liver disease: role of AMPK. Am J Physiol Endocrinol Metab. 2016;311:730-40.
  • Colak Y, Ozturk O, Senates E, Tuncer I, Yorulmaz E, Adali Gea. SIRT1 as a potential therapeutic target for treatment of nonalcoholic fatty liver disease. Med Sci Monit. 2011;17:5-9.
  • Luo X, He Z, Sun X, Gu X, Zhang W, Gao Jea. DHA protects against hepatic steatosis by activating Sirt1 in a high fat diet-induced nonalcoholic fatty liver disease mouse model. Diabetes Metab Syndr Obes. 2020;13:185-96.
  • Purushotham A, Schug T, Xu Q, Surapureddi S, Guo X, Li X. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab. 2009;9:327-38.
  • Horman S, Browne G, Krause U, Patel J, Vertommen D, Bertrand Lea. Activation of AMP-activated protein kinase leads to the phosphorylation of elongation factor 2 and an inhibition of protein synthesis. Curr Biol. 2002;12:1419-23.
  • Ashaq A, Maqbool, MF, Maryam, A, Khan, M, Shakir, HA, Irfan, M et al. Hispidulin: A novel natural compound with therapeutic potential against human cancers. Phytother Res. 2021;35:771-89.
  • Hwang J, Kwon D, Yoon S. AMP-activated protein kinase: a potential target for the diseases prevention by natural occurring polyphenols. N Biotechnol. 2009;26:17-22.
  • Tanyıldız S, Yıldırım H, Uğur H, Yaman M. AMPK’nın doğal aktivatörleri ve hastalıklarla ilişkisi. European Journal of Science and Technology. 2021:389-401.
  • Tekin M. Bodrum ve Marmara Adası'nda yetişen Salvia fruticosa (syn. Salvia triloba) bitkisinin polar ekstrelerinin kimyasal kompozisyonu ve biyoaktivitelerinin karşılaştırılması [Yüksek Lisans Tezi]. İstanbul: Bezmialem Vakıf Üniversitesi. 2022.
  • Wang K, Tan W, Liu X, Deng L, Huang L, Wang Xea. New insight and potential therapy for NAFLD: CYP2E1 and flavonoids. Biomed Pharmacother. 2021;137:111326.
  • Cederbaum A, Wu D, Mari M, Bai J. CYP2E1-dependent toxicity and oxidative stress in HepG2 cells. Free Radic Biol Med. 2001;31:1539-43.
  • Patel K, Patel D. Medicinal importance, pharmacological activities, and analytical aspects of hispidulin: A concise report. J Tradit Complement Med. 2017;7:360-66.
  • Wu X, Xu, J. New role of hispidulin in lipid metabolism: PPARα activator. Lipids. 2016;51:1249-57.
  • Lee SG, Kim JS, Min K, Kwon TK, Nam JO. Hispidulin inhibits adipogenesis in 3T3-L1 adipocytes through PPARγ pathway. Chem Biol Interact. 2018;293:89-93.
  • Ferrándiz M, Bustos G, Payá M, Gunasegaran R, Alcaraz M. Hispidulin protection against hepatotoxicity induced by bromobenzene in mice. Life Sci. 1994;55:145-50.
  • Jalilian A, Golmohammadi T, Meshkani R, Koushki M, Eivazi N, Khorzoughi Rea. Evaluating the effect of a mixture of two main conjugated linoleic acid isomers on hepatic steatosis in HepG2 cellular model. Mol Biol Rep. 2021;48:1359-70.
  • Zhao N, Li X, Wang L, Feng Z, Li X, Wen Yea. Palmitate induces fat accumulation by activating C/EBPβ-mediated G0S2 expression in HepG2 cells. World J Gastroenterol. 2017;23:7705-15.
  • Gambino R, Bugianesi E, Rosso C, Mezzabotta L, Pinach S, Alemanno Nea. Different serum free fatty acid profiles in NAFLD subjects and healthy controls after oral fat load. Int J Mol Sci. 2016;17:479.
  • Ricchi M, Odoardi M, Carulli L, Anzivino C, Ballestri S, Pinetti Aea. Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes. J Gastroenterol Hepatol. 2009;24:830-40.
  • Gnoni A, Di Chiara Stanca B, Giannotti L, Gnoni G, Siculella L, Damiano F. Quercetin reduces lipid accumulation in a cell model of NAFLD by inhibiting de novo fatty acid synthesis through the acetyl-coA carboxylase 1/AMPK/PP2A axis. Int J Mol Sci. 2022;23:1044.
  • Ziamajidi N, Khaghani S, Hassanzadeh G, Vardasbi S, Ahmadian S, Nowrouzi Aea. Amelioration by chicory seed extract of diabetes- and oleic acid-induced non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) via modulation of PPARα and SREBP-1. Food Chem Toxicol. 2013;58:198-209.
  • Lima K, Schneider Levorse V, Rosa Garcia M, de Souza Basso B, Pasqualotto Costa B, Antunes GLea. Octyl gallate induces hepatic steatosis in HepG2 cells through the regulation of SREBP-1c and PPAR-gamma gene expression. Excli j. 2020;19:962-71.
  • Donato M, Tolosa L, Gómez-Lechón M. Culture and functional characterization of human hepatoma HepG2 cells. Methods Mol Biol. 2015;1250:77-93.
  • Xia H, Zhu X, Zhang X, Jiang H, Li B, Wang Zea. Alpha-naphthoflavone attenuates non-alcoholic fatty liver disease in oleic acid-treated HepG2 hepatocytes and in high fat diet-fed mice. Biomed Pharmacother. 2019;118:109287.
  • Huang W, Chen Y, Liu H, Wu S, Liou C. Ginkgolide C reduced oleic acid-induced lipid accumulation in HepG2 cells. Saudi Pharm J. 2018;26:1178-84.
  • Lee D, Kwak H, Kim B, Kim S, Kim D, Kang K. Combined anti-adipogenic effects of hispidulin and p-synephrine on 3T3-L1 adipocytes. Biomolecules. 2021;11:1764.
  • Lee D, Lee, JH, Kim, BH, Lee, S, Kim, DW, Kang, KS. Phytochemical combination (p-synephrine, p-octopamine hydrochloride, and hispidulin) for improving obesity in obese mice induced by high-fat diet. Nutrients. 2022;14:2164.
  • Huang Y, Wang X, Yan C, Li C, Zhang L, Zhang Lea. Effect of metformin on nonalcoholic fatty liver based on meta-analysis and network pharmacology. Medicine. 2022;101:31437.
  • Acay A. Non alkolik yağlı karaciğer hastalığında güncel medikal tedavi. The medical journal of Kocatepe. 2015;16:67-76.
  • Liu Y, Li Y, Wang J, Yang L, Yu X, Huang Pea. Salvia-Nelumbinis naturalis improves lipid metabolism of NAFLD by regulating the SIRT1/AMPK signaling pathway. BMC Complement Med Ther. 2022;22:213.
  • Han M, Gao H, Ju P, Gao M, Yuan Y, Chen Xea. Hispidulin inhibits hepatocellular carcinoma growth and metastasis through AMPK and ERK signaling mediated activation of PPARγ. Biomed Pharmacother. 2018;103:272-83.
  • Wang Y, Liu W, He X, Fei Z. Hispidulin enhances the anti-tumor effects of temozolomide in glioblastoma by activating AMPK. Cell Biochem Biophys. 2015;71:701-6.
  • Niu X, Chen J, Wang P, Zhou H, Li S, Zhang M. The effects of hispidulin on bupivacaine-induced neurotoxicity: role of AMPK signaling pathway. Cell Biochem Biophys. 2014;70:241-9.
  • Huang L, Huang K, Ning H. Autophagy induction by hispidulin provides protection against sevoflurane-induced neuronal apoptosis in aged rats. Biomed Pharmacother. 2018;98:460-8.
  • Zhou R, Wang Z, Ma C. Hispidulin exerts anti-osteoporotic activity in ovariectomized mice via activating AMPK signaling pathway. Cell Biochem Biophys. 2014;69:311-7.
  • Woo S, Seo S, Kim S, Nam J, Kim S, Park Jea. Hispidulin enhances TRAIL-mediated apoptosis via CaMKKβ/AMPK/USP51 axis-mediated Bim stabilization. Cancers (Basel). 2019;11:1960.
  • Lin Y, Hung C, Tsai J, Lee J, Chen Y, Wei Cea. Hispidulin potently inhibits human glioblastoma multiforme cells through activation of AMP-activated protein kinase (AMPK). J Agric Food Chem. 2010;58:9511-7.
  • Kim J, Yang G, Kim Y, Kim J, Ha J. AMPK activators: mechanisms of action and physiological activities. Exp Mol Med. 2016;48:224.
  • Cheng J, Liu C, Hu K, Greenberg A, Wu D, Ausman Lea. Ablation of systemic SIRT1 activity promotes nonalcoholic fatty liver disease by affecting liver-mesenteric adipose tissue fatty acid mobilization. Biochim Biophys Acta Mol Basis Dis. 2017;1863:2783-90.
  • Patel DK, Patel K. Hepatoprotective effect of hispidulin for the treatment of non-alcoholic fatty liver disease (NAFLD): involvement of nuclear factor-κB and cytochrome p450 through molecular mechanism. The Liver Week 2020; Virtual Conference. p. 319

Hispidulin can improve lipid parameters in the HepG2 cell line with metabolic dysfunction-associated steatotic liver disease

Year 2024, Volume: 49 Issue: 4, 891 - 900, 30.12.2024
https://doi.org/10.17826/cumj.1520407

Abstract

Purpose: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant health issue. Although its pathogenesis remains unclear, insulin resistance, steatosis, and inflammation play crucial roles. Research on alternative treatment agents is ongoing. This is the first study to investigate the effect of hispidulin, a flavonoid, in a MASLD model.
Materials and Methods: Non-toxic concentrations of hispidulin and oleic acid were determined using the MTT cytotoxicity assay. Cells were first treated with hispidulin, followed by the addition of oleic acid two hours later. The cells were incubated for 24 hours to induce lipolysis. The intracellular lipids were demonstrated both qualitatively and quantitatively using Oil Red O staining. Triglyceride and total cholesterol levels, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) levels were measured.
Results: Hispidulin at 40 µM significantly reduced triglyceride levels by 67%, total cholesterol levels by 53%, ALT levels by 66%, and AST levels by 36%. However, no increase in AMPK or SIRT1 levels was observed compared to the model group.
Conclusion: Hispidulin can reduce cellular lipid accumulation, improve lipid parameters, and lower aminotransferase enzyme levels in MASLD. However, this effect may not occur via the AMPK-SIRT1 pathway but rather through other mechanisms. Further studies are needed to elucidate the mechanisms of hispidulin's action in MASLD.

Project Number

TF.UT.21.44

References

  • Powell E, Wong V, Rinella M. Non-alcoholic fatty liver disease. Lancet. 2021;397:2212-24.
  • Rinella M, Lazarus J, Ratziu V, Francque S, Sanyal A, Kanwal Fea. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023;78:1966-86.
  • Byrne C, Targher G. NAFLD: a multisystem disease. J Hepatol. 2015;62:47-64.
  • Kuyumcu A, Pürnak T, Yıldız E. Non alkolik yağlı karaciğer hastalığı olan bireylerde fruktoz tüketiminin değerlendirilmesi. Turk J Clin Lab. 2019;10:190-6.
  • Rong L, Zou J, Ran W, Qi X, Chen Y, Cui Hea. Advancements in the treatment of non-alcoholic fatty liver disease (NAFLD). Front Endocrinol (Lausanne). 2022;13:1087260.
  • Harrison S, Bedossa P, Guy C, Schattenberg J, Loomba R, Taub Rea. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N Engl J Med. 2024;390:497-509.
  • Ray K. Resmetirom proves positive for NASH with liver fibrosis. Nat Rev Gastroenterol Hepatol. 2024;21:218.
  • Wang S, Sheng F, Zou L, Xiao J, Li P. Hyperoside attenuates non-alcoholic fatty liver disease in rats via cholesterol metabolism and bile acid metabolism. J Adv Res. 2021;34:109-22.
  • Ipsen D, Lykkesfeldt J, Tveden-Nyborg P. Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease. Cell Mol Life Sci. 2018;75:3313-27.
  • Athyros V, Alexandrides T, Bilianou H, Cholongitas E, Doumas M, Ganotakis Eea. The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An expert panel statement. Metabolism. 2017;71:17-32.
  • Ünal N, Yılmaz F, Akarca U, Nart D, Ersöz G, Karasu Zea. Nonalkolik yağlı karaciğer hastalığında histolojik progresyon ile klinik ve laboratuvar parametrelerin ilişkisi. The Turkish Journal of Academic Gastroenterology. 2020;19:63-74.
  • Anggreini P, Kuncoro, H, Sumiwi, SA, Levita, J. Role of the AMPK/SIRT1 pathway in non‑alcoholic fatty liver disease (Review). Mol Med Rep. 2023;27:35.
  • Smith B, Marcinko K, Desjardins E, Lally J, Ford R, Steinberg G. Treatment of nonalcoholic fatty liver disease: role of AMPK. Am J Physiol Endocrinol Metab. 2016;311:730-40.
  • Colak Y, Ozturk O, Senates E, Tuncer I, Yorulmaz E, Adali Gea. SIRT1 as a potential therapeutic target for treatment of nonalcoholic fatty liver disease. Med Sci Monit. 2011;17:5-9.
  • Luo X, He Z, Sun X, Gu X, Zhang W, Gao Jea. DHA protects against hepatic steatosis by activating Sirt1 in a high fat diet-induced nonalcoholic fatty liver disease mouse model. Diabetes Metab Syndr Obes. 2020;13:185-96.
  • Purushotham A, Schug T, Xu Q, Surapureddi S, Guo X, Li X. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab. 2009;9:327-38.
  • Horman S, Browne G, Krause U, Patel J, Vertommen D, Bertrand Lea. Activation of AMP-activated protein kinase leads to the phosphorylation of elongation factor 2 and an inhibition of protein synthesis. Curr Biol. 2002;12:1419-23.
  • Ashaq A, Maqbool, MF, Maryam, A, Khan, M, Shakir, HA, Irfan, M et al. Hispidulin: A novel natural compound with therapeutic potential against human cancers. Phytother Res. 2021;35:771-89.
  • Hwang J, Kwon D, Yoon S. AMP-activated protein kinase: a potential target for the diseases prevention by natural occurring polyphenols. N Biotechnol. 2009;26:17-22.
  • Tanyıldız S, Yıldırım H, Uğur H, Yaman M. AMPK’nın doğal aktivatörleri ve hastalıklarla ilişkisi. European Journal of Science and Technology. 2021:389-401.
  • Tekin M. Bodrum ve Marmara Adası'nda yetişen Salvia fruticosa (syn. Salvia triloba) bitkisinin polar ekstrelerinin kimyasal kompozisyonu ve biyoaktivitelerinin karşılaştırılması [Yüksek Lisans Tezi]. İstanbul: Bezmialem Vakıf Üniversitesi. 2022.
  • Wang K, Tan W, Liu X, Deng L, Huang L, Wang Xea. New insight and potential therapy for NAFLD: CYP2E1 and flavonoids. Biomed Pharmacother. 2021;137:111326.
  • Cederbaum A, Wu D, Mari M, Bai J. CYP2E1-dependent toxicity and oxidative stress in HepG2 cells. Free Radic Biol Med. 2001;31:1539-43.
  • Patel K, Patel D. Medicinal importance, pharmacological activities, and analytical aspects of hispidulin: A concise report. J Tradit Complement Med. 2017;7:360-66.
  • Wu X, Xu, J. New role of hispidulin in lipid metabolism: PPARα activator. Lipids. 2016;51:1249-57.
  • Lee SG, Kim JS, Min K, Kwon TK, Nam JO. Hispidulin inhibits adipogenesis in 3T3-L1 adipocytes through PPARγ pathway. Chem Biol Interact. 2018;293:89-93.
  • Ferrándiz M, Bustos G, Payá M, Gunasegaran R, Alcaraz M. Hispidulin protection against hepatotoxicity induced by bromobenzene in mice. Life Sci. 1994;55:145-50.
  • Jalilian A, Golmohammadi T, Meshkani R, Koushki M, Eivazi N, Khorzoughi Rea. Evaluating the effect of a mixture of two main conjugated linoleic acid isomers on hepatic steatosis in HepG2 cellular model. Mol Biol Rep. 2021;48:1359-70.
  • Zhao N, Li X, Wang L, Feng Z, Li X, Wen Yea. Palmitate induces fat accumulation by activating C/EBPβ-mediated G0S2 expression in HepG2 cells. World J Gastroenterol. 2017;23:7705-15.
  • Gambino R, Bugianesi E, Rosso C, Mezzabotta L, Pinach S, Alemanno Nea. Different serum free fatty acid profiles in NAFLD subjects and healthy controls after oral fat load. Int J Mol Sci. 2016;17:479.
  • Ricchi M, Odoardi M, Carulli L, Anzivino C, Ballestri S, Pinetti Aea. Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes. J Gastroenterol Hepatol. 2009;24:830-40.
  • Gnoni A, Di Chiara Stanca B, Giannotti L, Gnoni G, Siculella L, Damiano F. Quercetin reduces lipid accumulation in a cell model of NAFLD by inhibiting de novo fatty acid synthesis through the acetyl-coA carboxylase 1/AMPK/PP2A axis. Int J Mol Sci. 2022;23:1044.
  • Ziamajidi N, Khaghani S, Hassanzadeh G, Vardasbi S, Ahmadian S, Nowrouzi Aea. Amelioration by chicory seed extract of diabetes- and oleic acid-induced non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) via modulation of PPARα and SREBP-1. Food Chem Toxicol. 2013;58:198-209.
  • Lima K, Schneider Levorse V, Rosa Garcia M, de Souza Basso B, Pasqualotto Costa B, Antunes GLea. Octyl gallate induces hepatic steatosis in HepG2 cells through the regulation of SREBP-1c and PPAR-gamma gene expression. Excli j. 2020;19:962-71.
  • Donato M, Tolosa L, Gómez-Lechón M. Culture and functional characterization of human hepatoma HepG2 cells. Methods Mol Biol. 2015;1250:77-93.
  • Xia H, Zhu X, Zhang X, Jiang H, Li B, Wang Zea. Alpha-naphthoflavone attenuates non-alcoholic fatty liver disease in oleic acid-treated HepG2 hepatocytes and in high fat diet-fed mice. Biomed Pharmacother. 2019;118:109287.
  • Huang W, Chen Y, Liu H, Wu S, Liou C. Ginkgolide C reduced oleic acid-induced lipid accumulation in HepG2 cells. Saudi Pharm J. 2018;26:1178-84.
  • Lee D, Kwak H, Kim B, Kim S, Kim D, Kang K. Combined anti-adipogenic effects of hispidulin and p-synephrine on 3T3-L1 adipocytes. Biomolecules. 2021;11:1764.
  • Lee D, Lee, JH, Kim, BH, Lee, S, Kim, DW, Kang, KS. Phytochemical combination (p-synephrine, p-octopamine hydrochloride, and hispidulin) for improving obesity in obese mice induced by high-fat diet. Nutrients. 2022;14:2164.
  • Huang Y, Wang X, Yan C, Li C, Zhang L, Zhang Lea. Effect of metformin on nonalcoholic fatty liver based on meta-analysis and network pharmacology. Medicine. 2022;101:31437.
  • Acay A. Non alkolik yağlı karaciğer hastalığında güncel medikal tedavi. The medical journal of Kocatepe. 2015;16:67-76.
  • Liu Y, Li Y, Wang J, Yang L, Yu X, Huang Pea. Salvia-Nelumbinis naturalis improves lipid metabolism of NAFLD by regulating the SIRT1/AMPK signaling pathway. BMC Complement Med Ther. 2022;22:213.
  • Han M, Gao H, Ju P, Gao M, Yuan Y, Chen Xea. Hispidulin inhibits hepatocellular carcinoma growth and metastasis through AMPK and ERK signaling mediated activation of PPARγ. Biomed Pharmacother. 2018;103:272-83.
  • Wang Y, Liu W, He X, Fei Z. Hispidulin enhances the anti-tumor effects of temozolomide in glioblastoma by activating AMPK. Cell Biochem Biophys. 2015;71:701-6.
  • Niu X, Chen J, Wang P, Zhou H, Li S, Zhang M. The effects of hispidulin on bupivacaine-induced neurotoxicity: role of AMPK signaling pathway. Cell Biochem Biophys. 2014;70:241-9.
  • Huang L, Huang K, Ning H. Autophagy induction by hispidulin provides protection against sevoflurane-induced neuronal apoptosis in aged rats. Biomed Pharmacother. 2018;98:460-8.
  • Zhou R, Wang Z, Ma C. Hispidulin exerts anti-osteoporotic activity in ovariectomized mice via activating AMPK signaling pathway. Cell Biochem Biophys. 2014;69:311-7.
  • Woo S, Seo S, Kim S, Nam J, Kim S, Park Jea. Hispidulin enhances TRAIL-mediated apoptosis via CaMKKβ/AMPK/USP51 axis-mediated Bim stabilization. Cancers (Basel). 2019;11:1960.
  • Lin Y, Hung C, Tsai J, Lee J, Chen Y, Wei Cea. Hispidulin potently inhibits human glioblastoma multiforme cells through activation of AMP-activated protein kinase (AMPK). J Agric Food Chem. 2010;58:9511-7.
  • Kim J, Yang G, Kim Y, Kim J, Ha J. AMPK activators: mechanisms of action and physiological activities. Exp Mol Med. 2016;48:224.
  • Cheng J, Liu C, Hu K, Greenberg A, Wu D, Ausman Lea. Ablation of systemic SIRT1 activity promotes nonalcoholic fatty liver disease by affecting liver-mesenteric adipose tissue fatty acid mobilization. Biochim Biophys Acta Mol Basis Dis. 2017;1863:2783-90.
  • Patel DK, Patel K. Hepatoprotective effect of hispidulin for the treatment of non-alcoholic fatty liver disease (NAFLD): involvement of nuclear factor-κB and cytochrome p450 through molecular mechanism. The Liver Week 2020; Virtual Conference. p. 319
There are 52 citations in total.

Details

Primary Language English
Subjects Gastroenterology and Hepatology
Journal Section Research
Authors

Bircan Aslan 0000-0002-3052-6690

Davut Sinan Kaplan 0000-0003-4663-209X

Hasan Ulusal 0000-0003-3890-2088

Mehmet Tarakçıoğlu 0000-0002-2398-8264

Project Number TF.UT.21.44
Publication Date December 30, 2024
Submission Date July 22, 2024
Acceptance Date October 23, 2024
Published in Issue Year 2024 Volume: 49 Issue: 4

Cite

MLA Aslan, Bircan et al. “Hispidulin Can Improve Lipid Parameters in the HepG2 Cell Line With Metabolic Dysfunction-Associated Steatotic Liver Disease”. Cukurova Medical Journal, vol. 49, no. 4, 2024, pp. 891-00, doi:10.17826/cumj.1520407.