Effects of Phloretin on Bisphenol-A Induced Liver and Kidney Toxicity in Prepubertal Female Rats
Yıl 2023,
Cilt: 82 Sayı: 2, 212 - 223, 21.12.2023
Eda Nur İnkaya
,
Nilüfer Coşkun Kılıç
,
Nurhayat Barlas
Öz
Objective: The aim of this study was to investigate the protective effects of phloretin against bisphenol-A (BPA)-induced liver and kidney damage in rats using histopathological and biochemical parameters.
Materials and Methods: This study started on female rats on the postnatal 28th day via subcutaneous injection by dissolving the compounds in corn oil at 30-min intervals, starting with phloretin, and followed by BPA. The dose of BPA was 50 mg/kg bw/day, and the doses of phloretin were 0.5, 5, and 50 mg/kg bw/day. Treatments were administered every day for 15 days. Histopathological, morphometric, and biochemical parameters were analyzed.
Results: Histopathological evaluation revealed tubular degeneration, fibrous tissue formation, congestion, and edema in the kidney tissue and cellular degeneration and congestion in the liver tissue. BPA treatment resulted in a statistically significant increase in serum urea and alanine aminotransferase levels and a decrease in serum glucose and aspartate aminotransferase levels. Against these effects of BPA, a positive effect was detected only on serum urea levels in rats treated with 50 mg/kg bw/day phloretin. There was also no significant change in serum triglyceride, creatinine, and albumin levels in the BPA positive control group. The renal morphometric analysis revealed that treatment with 0.5 mg/kg bw/day phloretin reduced the BPA-induced glomerular damage.
Conclusion: Biochemical parameters and histopathological findings in the kidney and liver tissues revealed no clear evidence of a protective effect of phloretin against the damage caused by BPA. Hence, phloretin exhibits a low level of protection against liver and kidney damage.
Etik Beyan
Permission required for the studies was obtained from Hacettepe University Experimental Animals Ethics Committee with the number 2018/47-04.
Destekleyen Kurum
The authors disclosed receipt of the following financial support for the research of this article: This work was supported by the Scientific Research Projects Coordination Unit of Hacettepe University [Project No: FHD-2019- 17619]. Eda Nur İNKAYA is supported by the Council of Higher Education (YÖK), Turkey within the scope of the YÖK 100/2000 Ph.D. Scholarship.
Proje Numarası
Project No: FHD-2019- 17619
Teşekkür
This work was supported by the Scientific Research Projects Coordination Unit of Hacettepe University [Project No: FHD-2019- 17619].
Kaynakça
- Monneret C. What is an endocrine disruptor? C R Biol. 2017;340(9-10):403-405. google scholar
- Batool S, Batool S, Shameem S, Batool T, Batool S. Effects of dibutyl phthalate and di (2-ethylhexyl) phthalate on the hep-atic structure and function of adult male mice. Toxicol Industrial Health. 2022;38(8):470-480. google scholar
- İnkaya EN, Barlas N. Investigation of the combined effects of propylparaben and methylparaben on biochemical and histologi-cal parameters in male rats. J Clin Pract Res. 2023;45(4):360-369. google scholar
- Rutkowska A, Rachon D. Bisphenol A (BPA) and its potential role in the pathogenesis of the polycystic ovary syndrome (PCOS). Gynecol Endocrinol. 2014;30(4):260-265. google scholar
- Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, et al. Endocrine-disrupting chemicals: An Endocrine Society scientific statement. Endocr Rev. 2009;30(4):293-342. google scholar
- International Food Safety Authorities Network (INFOSAN). Bisphenol A (BPA) - Current state of knowledge and future ac-tions by WHO and FAO. 2009;1-6. google scholar
- Abbas MAM, Elmetwally SAF, Mokhtar Abo-Elfotoh, MA. Effect of oral exposure to bisphenol a on the liver and kidney of adult male albino rats. Int J Med Arts. 2021;3(1):930-937. google scholar
- Abdulhameed AAR, Lim V, Bahari H, et al. Adverse effects of bisphenol a on the liver and its underlying mechanisms: evidence from in vivo and in vitro studies. Biomed Res Int. 2022;16:8227314. doi:10.1155/2022/8227314 google scholar
- İnanç N, Tuna Ş. Fitoöstrojenler ve sağlıktaki etkileri. Erciyes Üniv Vet Fak Derg. 2005;2(2):91-95. google scholar
- Shen X, Wang L, Zhou N, Gai S, Liu X, Zhang S. Beneficial effects of combination therapy of phloretin and metformin in streptozotocin-induced diabetic rats and improved insulin sensi-tivity: In vitro. Food Funct. 2020;11(1):392-403. google scholar
- Yang EB, Guo YJ, Zhang K, Chen YZ, Mack P. Inhibition of epi-dermal growth factor receptor tyrosine kinase by chalcone deriva-tives. Biochim Biophy Acta. 2001;1550(2):144-152. google scholar
- Andrade PB, Barbosa M, Matos RP, et al. Valuable compounds in macroalgae extracts. Food Chem. 2013;138(2-3):1819-1828. google scholar
- Nielsen ILF, Williamson G. Review of the factors affecting bioavailability of soy isoflavones in humans. Nutr Cancer. 2007;57(1):1-10. google scholar
- Arts ICW, Hollman PCH. Polyphenols and disease risk in epi-demiologic studies. Am J Clin Nutr. 2005;81(1):317-325. google scholar
- Kabir I, Rahman ER, Rahman MS. A review on endocrine disrup-tors and their possible impacts on human health. Environ Toxicol Pharmacol. 2015;40:241-258. google scholar
- Yıldız N, Barlas N. Hepatic and renal functions in growing male rats after bisphenol A and octylphenol exposure. Human Exp Toxicol. 2013;32(7):675-86. google scholar
- Nakhate KT, Badwaik H, Choudhary R, et al. Therapeutic poten-tial and pharmaceutical development of a multi targeted flavonoid phloretin. Nutrients. 2022;14(17):3638. doi:10.3390/nu14173638 google scholar
- Geohagen BC, Korsharskyy B, Vydyanatha A, Nordstroem L, LoPachin RM. Phloretin cytoprotection and toxicity. Chem Biol Interact. 2018; 296:117-123. google scholar
- Alansari WS, Eskandrani AA. The anticarcinogenic effect of the apple polyphenol phloretin in an experimental rat model of hep-atocellular carcinoma. Arab J Sci Eng. 2020;45:4589-4597. google scholar
- Moselhy W, Ahmed WMS, Moselhy WA, Nabil TM. Bisphenol A toxicity in adult male rats: hematological, biochemical and histopathological approach. Glob Vet. 2015;14(2):228-238 google scholar
- Zuo AR, Yu YY, Shu QL, et al. Hepatoprotective effects and antioxidant, antityrosinase activities of phloretin and phloretin isonicotinyl hydrazone. J Chin Med Assoc. 2014;77(6):290-301. google scholar
- Ren D, Liu Y, Zhao Y, Yang X. Hepatotoxicity and endothelial dysfunction induced by high choline diet and the protective effects of phloretin in mice. Food Chem Toxicol. 2016;94:203-212. google scholar
- Lu Y, Chen J, Ren D, Yang X, Zhao Y. Hepatoprotective effects of phloretin against CCl4-induced liver injury in mice. Food Agric Immunol. 2017;28(2):211-222. google scholar
- Chhimwal J, Goel A, Sukapaka M, Patial V, Padwad Y. Phloretin mitigates oxidative injury, inflammation, and fibrogenic re-sponses via restoration of autophagic flux in in vitro and pre-clinical models of NAFLD. J Nutr Biochem. 2022;107:109062. doi:10.1016/j.jnutbio.2022.109062 google scholar
- Shu G, Lu NS, Zhu XT, et al. Phloretin promotes adipocyte dif-ferentiation in vitro and improves glucose homeostasis in vivo. J Nutr Biochem. 2014;25(12):1296-1308. google scholar
- Shen X, Zhou N, Mi L, et al. Phloretin exerts hypoglycemic effect in streptozotocin-induced diabetic rats and improves insulin resistance in vitro. Drug Des Devel Ther. 2017;11:313-324. google scholar
- Alsanea S, Gao M, Liu D. Phloretin prevents high-fat diet-induced obesity and improves metabolic homeostasis. AAPS J. 2017;19(3):797-805. google scholar
- Mao W, Fan Y, Wang X, et al. Phloretin ameliorates diabetes-induced endothelial injury through AMPK-dependent anti-EndMT pathway. Pharmacol Res. 2022;179:106205. doi:10.1016/j.phrs.2022.106205 google scholar
- Schulze C, Bangert A, Kottra G, et al. Inhibition of the intestinal sodium-coupled glucose transporter 1 (SGLT1) by extracts and polyphenols from apple reduces postprandial blood glucose levels in mice and humans. Mol Nutr Food Res. 2014;58(9):1795-1808. google scholar
- Kellett GL, Helliwell PA. The diffusive component of intesti-nal glucose absorption is mediated by the glucose-induced re-cruitment of GLUT2 to the brush-border membrane. Biochem J. 2000;350:155-162. google scholar
- Tahrani AA, Barnett AH, Bailey CJ. SGLT inhibitors in manage-ment of diabetes. Lancet Diabetes Endocrinol. 2013;1:140-151. google scholar
- Osorio H, Bautista R, Rios A, et al. Effect of phlorizin on SGLT2 expression in the kidney of diabetic rats. J Nephrol. 2010;23(5):541-546. google scholar
- Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev. 2000;80(3):1107-1213. google scholar
- Beriry HM, Atef K, Gaber AS, Mohi ElDin MM. Ameliorative effect of mushroom extracts against butyl paraben induced toxi-city in liver and kidney in female albino rats. SVU-Int J Vet Sci. 2022;5(2):11-22. google scholar
- Zhao Y, Dai W. Effect of phloretin treatment ameliorated the cisplatin-induced nephrotoxicity and oxidative stress in experi-mental rats. Pharmacogn Mag. 2020;(16):207-213. google scholar
- UnH, Ugan RA, Gurbuz MA, et al. Phloretin and phloridzin guard against cisplatin-induced nephrotoxicity in mice through inhibit-ing oxidative stress and inflammation. Life Sci. 2021;266:118869. doi:10.1016/j.lfs.2020.118869 google scholar
- Pujari NM, Mishra A, Khushtar M. i and histological toxic-ity profiling of a natural phenol: Phloretin. Neuroquantology. 2022;20(16):843-850. google scholar
- Aliomrani M, Sepand MR, Mirzaei HR, Kazemi AR, Nekonam S, Sabzevari O. Effects of phloretin on oxidative and inflammatory reaction in rat model of cecal ligation and puncture induced sepsis. Daru. 2016;24(1):15. doi:10.1186/s40199-016-0154-9 google scholar
- Cui D, Liu S, Tang M, et al. Phloretin ameliorates hyperuricemia-induced chronic renal dysfunction through inhibiting NLRP3 inflammasome and uric acid reabsorption. Phytomedicine. 2020;66:153111. doi:10.1016/j.phymed.2019.153111 google scholar
- Galluzzo P, Marino M. Nutritional flavonoids impact on nu-clear and extranuclear estrogen receptor activities. Genes Nutr. 2006;1(3-4):161-176. google scholar
- Cornwell T. Dietary phytoestrogens and health. Phytochemistry. 2004;6(8):995-1016. google scholar
- Washington IM, Van Hoosier G. Clinical Biochemistry and Hema-tology. In: Suckow MA, Stevens KA, Wilson RP, eds. In American College of Laboratory Animal Medicine, The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents. Academic Press.2012; 57-116, google scholar
- Ihedioha JI, Noel-Uneke OA, Ihedioha TE. Reference values for the serum lipid profile of albino rats (Rattus norvegicus) of varied ages and sexes. Comp Clin Path. 2013;22:93-99. google scholar
- Mesomya W, Hengsawadi D, Cuptapun Y, Jittanoonta P, Thalang VN. Effect of age on serum cholesterol and triglyceride levels in the experimental rats. Agric Nat Resour. 2001;35(2):144-148. google scholar
- Christie WW, Han X. Lipid Analysis. Oily Press Lipid Library Series. 2012;3-19. google scholar
- Anraku M, Yamasaki K, Maruyama T, Kragh-Hansen U, Otagiri M. Effect of oxidative stress on the structure and function of human serum albumin. Pharm Res. 2001;18(5):632-639. google scholar
- Ranich T, Bhathena SJ, Velasquez MT. Protective effects of dietary phytoestrogens in chronic renal disease. J Ren Nutr. 2001;11:183-193. google scholar
- Itou da Silva FS, Veiga Bizerra PF, Mito MS, et al.The metabolic and toxic acute effects of phloretin in the rat liver. Chem Biol Interact. 2022;364:110054. doi:10.1016/j.cbi.2022.110054 google scholar
- Zhao YY, Fan Y, Wang M, et al. Studies on pharmacoki-netic properties and absorption mechanism of phloretin: In vivo and in vitro. Biomed Pharmacother. 2020;132:110809. doi:10.1016/j.biopha.2020.110809 google scholar
- Guo D, Liu J, Fan Y, Cheng J, et al., Optimization, characteriza-tion and evaluation of liposomes from Malus hupehensis (Pamp.) Rehd. Extracts. J Liposome Res. 2019;30(4):1-11. google scholar
- Sharifi-Rad A, Mehrzad J, Darroudi M, Saberi MR, Chamani J. Oil-in-water nano emulsions comprising Berberine in olive oil: Biological activities, binding mechanisms to human serum albumin or holo-transferrin and QMMD simulations. J Biomol Struct Dyn. 2021;39(3):1029-1043. google scholar
Yıl 2023,
Cilt: 82 Sayı: 2, 212 - 223, 21.12.2023
Eda Nur İnkaya
,
Nilüfer Coşkun Kılıç
,
Nurhayat Barlas
Proje Numarası
Project No: FHD-2019- 17619
Kaynakça
- Monneret C. What is an endocrine disruptor? C R Biol. 2017;340(9-10):403-405. google scholar
- Batool S, Batool S, Shameem S, Batool T, Batool S. Effects of dibutyl phthalate and di (2-ethylhexyl) phthalate on the hep-atic structure and function of adult male mice. Toxicol Industrial Health. 2022;38(8):470-480. google scholar
- İnkaya EN, Barlas N. Investigation of the combined effects of propylparaben and methylparaben on biochemical and histologi-cal parameters in male rats. J Clin Pract Res. 2023;45(4):360-369. google scholar
- Rutkowska A, Rachon D. Bisphenol A (BPA) and its potential role in the pathogenesis of the polycystic ovary syndrome (PCOS). Gynecol Endocrinol. 2014;30(4):260-265. google scholar
- Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, et al. Endocrine-disrupting chemicals: An Endocrine Society scientific statement. Endocr Rev. 2009;30(4):293-342. google scholar
- International Food Safety Authorities Network (INFOSAN). Bisphenol A (BPA) - Current state of knowledge and future ac-tions by WHO and FAO. 2009;1-6. google scholar
- Abbas MAM, Elmetwally SAF, Mokhtar Abo-Elfotoh, MA. Effect of oral exposure to bisphenol a on the liver and kidney of adult male albino rats. Int J Med Arts. 2021;3(1):930-937. google scholar
- Abdulhameed AAR, Lim V, Bahari H, et al. Adverse effects of bisphenol a on the liver and its underlying mechanisms: evidence from in vivo and in vitro studies. Biomed Res Int. 2022;16:8227314. doi:10.1155/2022/8227314 google scholar
- İnanç N, Tuna Ş. Fitoöstrojenler ve sağlıktaki etkileri. Erciyes Üniv Vet Fak Derg. 2005;2(2):91-95. google scholar
- Shen X, Wang L, Zhou N, Gai S, Liu X, Zhang S. Beneficial effects of combination therapy of phloretin and metformin in streptozotocin-induced diabetic rats and improved insulin sensi-tivity: In vitro. Food Funct. 2020;11(1):392-403. google scholar
- Yang EB, Guo YJ, Zhang K, Chen YZ, Mack P. Inhibition of epi-dermal growth factor receptor tyrosine kinase by chalcone deriva-tives. Biochim Biophy Acta. 2001;1550(2):144-152. google scholar
- Andrade PB, Barbosa M, Matos RP, et al. Valuable compounds in macroalgae extracts. Food Chem. 2013;138(2-3):1819-1828. google scholar
- Nielsen ILF, Williamson G. Review of the factors affecting bioavailability of soy isoflavones in humans. Nutr Cancer. 2007;57(1):1-10. google scholar
- Arts ICW, Hollman PCH. Polyphenols and disease risk in epi-demiologic studies. Am J Clin Nutr. 2005;81(1):317-325. google scholar
- Kabir I, Rahman ER, Rahman MS. A review on endocrine disrup-tors and their possible impacts on human health. Environ Toxicol Pharmacol. 2015;40:241-258. google scholar
- Yıldız N, Barlas N. Hepatic and renal functions in growing male rats after bisphenol A and octylphenol exposure. Human Exp Toxicol. 2013;32(7):675-86. google scholar
- Nakhate KT, Badwaik H, Choudhary R, et al. Therapeutic poten-tial and pharmaceutical development of a multi targeted flavonoid phloretin. Nutrients. 2022;14(17):3638. doi:10.3390/nu14173638 google scholar
- Geohagen BC, Korsharskyy B, Vydyanatha A, Nordstroem L, LoPachin RM. Phloretin cytoprotection and toxicity. Chem Biol Interact. 2018; 296:117-123. google scholar
- Alansari WS, Eskandrani AA. The anticarcinogenic effect of the apple polyphenol phloretin in an experimental rat model of hep-atocellular carcinoma. Arab J Sci Eng. 2020;45:4589-4597. google scholar
- Moselhy W, Ahmed WMS, Moselhy WA, Nabil TM. Bisphenol A toxicity in adult male rats: hematological, biochemical and histopathological approach. Glob Vet. 2015;14(2):228-238 google scholar
- Zuo AR, Yu YY, Shu QL, et al. Hepatoprotective effects and antioxidant, antityrosinase activities of phloretin and phloretin isonicotinyl hydrazone. J Chin Med Assoc. 2014;77(6):290-301. google scholar
- Ren D, Liu Y, Zhao Y, Yang X. Hepatotoxicity and endothelial dysfunction induced by high choline diet and the protective effects of phloretin in mice. Food Chem Toxicol. 2016;94:203-212. google scholar
- Lu Y, Chen J, Ren D, Yang X, Zhao Y. Hepatoprotective effects of phloretin against CCl4-induced liver injury in mice. Food Agric Immunol. 2017;28(2):211-222. google scholar
- Chhimwal J, Goel A, Sukapaka M, Patial V, Padwad Y. Phloretin mitigates oxidative injury, inflammation, and fibrogenic re-sponses via restoration of autophagic flux in in vitro and pre-clinical models of NAFLD. J Nutr Biochem. 2022;107:109062. doi:10.1016/j.jnutbio.2022.109062 google scholar
- Shu G, Lu NS, Zhu XT, et al. Phloretin promotes adipocyte dif-ferentiation in vitro and improves glucose homeostasis in vivo. J Nutr Biochem. 2014;25(12):1296-1308. google scholar
- Shen X, Zhou N, Mi L, et al. Phloretin exerts hypoglycemic effect in streptozotocin-induced diabetic rats and improves insulin resistance in vitro. Drug Des Devel Ther. 2017;11:313-324. google scholar
- Alsanea S, Gao M, Liu D. Phloretin prevents high-fat diet-induced obesity and improves metabolic homeostasis. AAPS J. 2017;19(3):797-805. google scholar
- Mao W, Fan Y, Wang X, et al. Phloretin ameliorates diabetes-induced endothelial injury through AMPK-dependent anti-EndMT pathway. Pharmacol Res. 2022;179:106205. doi:10.1016/j.phrs.2022.106205 google scholar
- Schulze C, Bangert A, Kottra G, et al. Inhibition of the intestinal sodium-coupled glucose transporter 1 (SGLT1) by extracts and polyphenols from apple reduces postprandial blood glucose levels in mice and humans. Mol Nutr Food Res. 2014;58(9):1795-1808. google scholar
- Kellett GL, Helliwell PA. The diffusive component of intesti-nal glucose absorption is mediated by the glucose-induced re-cruitment of GLUT2 to the brush-border membrane. Biochem J. 2000;350:155-162. google scholar
- Tahrani AA, Barnett AH, Bailey CJ. SGLT inhibitors in manage-ment of diabetes. Lancet Diabetes Endocrinol. 2013;1:140-151. google scholar
- Osorio H, Bautista R, Rios A, et al. Effect of phlorizin on SGLT2 expression in the kidney of diabetic rats. J Nephrol. 2010;23(5):541-546. google scholar
- Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev. 2000;80(3):1107-1213. google scholar
- Beriry HM, Atef K, Gaber AS, Mohi ElDin MM. Ameliorative effect of mushroom extracts against butyl paraben induced toxi-city in liver and kidney in female albino rats. SVU-Int J Vet Sci. 2022;5(2):11-22. google scholar
- Zhao Y, Dai W. Effect of phloretin treatment ameliorated the cisplatin-induced nephrotoxicity and oxidative stress in experi-mental rats. Pharmacogn Mag. 2020;(16):207-213. google scholar
- UnH, Ugan RA, Gurbuz MA, et al. Phloretin and phloridzin guard against cisplatin-induced nephrotoxicity in mice through inhibit-ing oxidative stress and inflammation. Life Sci. 2021;266:118869. doi:10.1016/j.lfs.2020.118869 google scholar
- Pujari NM, Mishra A, Khushtar M. i and histological toxic-ity profiling of a natural phenol: Phloretin. Neuroquantology. 2022;20(16):843-850. google scholar
- Aliomrani M, Sepand MR, Mirzaei HR, Kazemi AR, Nekonam S, Sabzevari O. Effects of phloretin on oxidative and inflammatory reaction in rat model of cecal ligation and puncture induced sepsis. Daru. 2016;24(1):15. doi:10.1186/s40199-016-0154-9 google scholar
- Cui D, Liu S, Tang M, et al. Phloretin ameliorates hyperuricemia-induced chronic renal dysfunction through inhibiting NLRP3 inflammasome and uric acid reabsorption. Phytomedicine. 2020;66:153111. doi:10.1016/j.phymed.2019.153111 google scholar
- Galluzzo P, Marino M. Nutritional flavonoids impact on nu-clear and extranuclear estrogen receptor activities. Genes Nutr. 2006;1(3-4):161-176. google scholar
- Cornwell T. Dietary phytoestrogens and health. Phytochemistry. 2004;6(8):995-1016. google scholar
- Washington IM, Van Hoosier G. Clinical Biochemistry and Hema-tology. In: Suckow MA, Stevens KA, Wilson RP, eds. In American College of Laboratory Animal Medicine, The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents. Academic Press.2012; 57-116, google scholar
- Ihedioha JI, Noel-Uneke OA, Ihedioha TE. Reference values for the serum lipid profile of albino rats (Rattus norvegicus) of varied ages and sexes. Comp Clin Path. 2013;22:93-99. google scholar
- Mesomya W, Hengsawadi D, Cuptapun Y, Jittanoonta P, Thalang VN. Effect of age on serum cholesterol and triglyceride levels in the experimental rats. Agric Nat Resour. 2001;35(2):144-148. google scholar
- Christie WW, Han X. Lipid Analysis. Oily Press Lipid Library Series. 2012;3-19. google scholar
- Anraku M, Yamasaki K, Maruyama T, Kragh-Hansen U, Otagiri M. Effect of oxidative stress on the structure and function of human serum albumin. Pharm Res. 2001;18(5):632-639. google scholar
- Ranich T, Bhathena SJ, Velasquez MT. Protective effects of dietary phytoestrogens in chronic renal disease. J Ren Nutr. 2001;11:183-193. google scholar
- Itou da Silva FS, Veiga Bizerra PF, Mito MS, et al.The metabolic and toxic acute effects of phloretin in the rat liver. Chem Biol Interact. 2022;364:110054. doi:10.1016/j.cbi.2022.110054 google scholar
- Zhao YY, Fan Y, Wang M, et al. Studies on pharmacoki-netic properties and absorption mechanism of phloretin: In vivo and in vitro. Biomed Pharmacother. 2020;132:110809. doi:10.1016/j.biopha.2020.110809 google scholar
- Guo D, Liu J, Fan Y, Cheng J, et al., Optimization, characteriza-tion and evaluation of liposomes from Malus hupehensis (Pamp.) Rehd. Extracts. J Liposome Res. 2019;30(4):1-11. google scholar
- Sharifi-Rad A, Mehrzad J, Darroudi M, Saberi MR, Chamani J. Oil-in-water nano emulsions comprising Berberine in olive oil: Biological activities, binding mechanisms to human serum albumin or holo-transferrin and QMMD simulations. J Biomol Struct Dyn. 2021;39(3):1029-1043. google scholar