The effects of herbal cream and silymarin on liver in carbon tetrachloride-treated animals
Year 2025,
Volume: 72 Issue: 1, 47 - 57
Asli Kandil
,
Aysu Kılıc
,
Ebru Gürel Gürevin
,
İbrahim Söğüt
,
Savaş Üstünova
,
Şeyma Eren
,
Metin Caner
,
Cihan Demirci Tansel
Abstract
Many medical or pharmaceutical plants have been widely used for the treatment of the liver injury. Silymarin is now used as a food-supporting material for the liver as a patented product. Herbal cream has anti-inflammatory and antioxidant effects on wound healing in a hemorrhoid model. This study aimed to evaluate the effects of herbal cream and silymarin on the liver in carbon tetrachloride (CCl4)-treated animals. Male Wistar rats were divided into seven groups as Intact control, Control, Herbal cream (0.5 ml, intrarectal), Silymarin (70 mg/kg, intrarectal), CCl4 (2 ml/kg, intraperitoneal), CCl4+Herbal cream (0.5 ml herbal cream for 21 days, 3 weeks after administration of CCl₄) and CCl4+Silymarin (70 mg/kg silymarin for 21 days, 3 weeks after administration of CCl₄). Herbal cream reduced damage and leukocyte distribution induced by CCl4 and increased catalase. There was no significant change in superoxide dismutase (SOD) and glutathione peroxidase (GPx). The levels of SOD, catalase, and GPx in the liver increased significantly in the group treated only with herbal cream. These results point out that herbal cream may have antioxidant properties in the liver and a role in preventing liver damage. As a result, it has been detected that herbal cream is not a toxic agent and recovers liver damage with antioxidant properties.
Ethical Statement
This study was approved by the Istanbul University Local Committee on Animal Research Ethics (Decision no: 2013/92).
Supporting Institution
This study was supported by the Scientific Research Projects Coordination Unit of Istanbul University. Project No: 37789.
Thanks
The authors would like to thank Feyyaz Küçükay for the drug preparation.
References
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- Abenavoli L, Izzo AA, Milić N, et al (2018): Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Phytother Res, 32, 2202-2213.
- Aghel N, Kalantari H, Rezazadeh S (2011): Hepatoprotective effect of Ficus carica leaf extract on mice intoxicated with carbon tetrachloride. Iran J Pharm Res, 10, 63-68.
- Ali B, Mujeeb M, Aeri V, et al (2012): Anti-inflammatory and antioxidant activity of Ficus carica Linn. Leaves. Nat Prod Res, 26, 460-465.
- Al-Olayan EM, El-Khadragy MF, Aref AM, et al (2014): The potential protective effect of Physalis peruviana L. against carbon tetrachloride-induced hepatotoxicity in rats is mediated by suppression of oxidative stress and downregulation of MMP-9 expression. Oxid Med Cell Longev, 2014, 381413.
- Al-Rasheed N, Faddah L, Al-Rasheed N, et al (2016): Protective effects of silymarin, alone or in combination with chlorogenic acid and/or melatonin, against carbon tetrachloride-induced hepatotoxicity. Pharmacogn Mag, 12, S337-S345.
- Alshatwi AA, Hasan TN, Shafi G, et al (2012): Validation of the antiproliferative effects of organic extracts from the green husk of Juglans regia L. on PC-3 human prostate cancer cells by assessment of apoptosis-related genes. Evid Based Complement Alternat Med, 2012, 103026.
- Aslan A, Can MI (2014): Milk thistle impedes the development of carbontetrachloride-induced liver damage in rats through suppression of bcl-2 and regulating caspase pathway. Life Sci, 117, 13-18.
- Aydın S, Gökçe Z, Yılmaz Ö (2015): The effects of Juglans regia L. (walnut) extract on certain biochemical paramaters and in the prevention of tissue damage in brain, kidney, and liver in CCl4 applied Wistar rats. Turk J Biochem, 40, 241-250.
- Beutler E (1982): Red cell metabolism: A manual of biochemical methods. 3rd edition. Grune and Stratton; New York.
- Bradford MM (1976): A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem, 72, 248-254.
- Clawson GA (1989): Mechanisms of carbon tetrachloride hepatotoxicity. Pathol Immunopathol Res, 8, 104-112.
- Colak E, Ustuner MC, Tekin N, et al (2016): The hepatocurative effects of Cynara scolymus L. leaf extract on carbon tetrachloride-induced oxidative stress and hepatic injury in rats. Springerplus, 5, 216.
- De La Puerta R, Martinez E, Bravo L, et al (1996): Effect of silymarin on different acute inflammation models and on leukocyte migration. J Pharm Pharmacol, 48, 968-670.
- Demirci C, Gargili A, Kandil A, et al (2006): Inhibition of inducible nitric oxide synthase in murine visceral larva migrans: effects on lung and liver damage. Chin J Physiol, 49, 326-334.
- Donga D, Xua L, Yina L, et al (2015): Naringin prevents carbon tetrachloride-induced acute liver injury in mice. J Funct Foods, 12, 179-191.
- Eassawy MMT, Ismail AFM (2024): Protective effect of chicory and/or artichoke leaves extracts on carbon tetrachloride and gamma-irradiation-induced chronic nephrotoxicity in rats. Environmental Toxicology, 39, 1666-1681.
- Eidi A, Moghadam JZ, Mortazavi P, et al (2013): Hepatoprotective effects of Juglans regia extract against CCl4-induced oxidative damage in rats. Pharm Biol, 51, 558-565.
- El-Boshy M, Ashshi A, Gaith M, et al (2017): Studies on the protective effect of the artichoke (Cynara scolymus) leaf extract against cadmium toxicity-induced oxidative stress, hepatorenal damage, and immunosuppressive and hematological disorders in rats. Environ Sci Pollut Res Int, 24, 12372-12383.
- Elmas O, Erbas O, Yigitturk G (2016): The efficacy of Aesculus hippocastanum seeds on diabetic nephropathy in a streptozotocin-induced diabetic rat model. Biomed Pharmacother, 83, 392-396.
- Florek E, Szukalska M, Markiewicz K, et al (2023): Evaluation of the protective and regenerative properties of commercially available artichoke leaf powder extract on plasma and liver oxidative stress parameters. Antioxidants (Basel), 12, 1846.
- Gebhardt R (1997): Antioxidative and protective properties of extracts from leaves of the artichoke (Cynara scolymus L.) against hydroperoxide-induced oxidative stress in cultured rat hepatocytes. Toxicol Appl Pharmacol, 144, 279-286.
- Guarrera PM (2005): Traditional phytotherapy in Central Italy (Marche, Abruzzo, and Latium). Fitoterapia, 76, 1-25.
- Gurel E, Ustunova S, Ergin B, et al (2013): Herbal haemorrhoidal cream for haemorrhoids. Chin J Physiol, 56, 253-262.
- Haque R, Bin-Hafeez B, Parvez S, et al (2003): Aqueous extract of walnut (Juglans regia L.) protects mice against cyclophosphamide-induced biochemical toxicity. Hum Exp Toxicol, 22, 473-480.
- Hosseini SA, Mohammadi J, Delaviz H, et al (2018): Effect of Juglans regia and Nasturtum officinalis biochemical parameters following toxicity of kidney by CCl4 in Wistar rats. Electronic Journal of General Medicine, 15.
- Jiang G, Sun C, Wang X, et al (2022): Hepatoprotective mechanism of Silybum marianum on nonalcoholic fatty liver disease based on network pharmacology and experimental verification. Bioengineered, 13, 5216-5235.
- Jiang N, Xin W, Wang T, et al (2011): Protective effect of aescin from the seeds of Aesculus hippocastanum on liver injury induced by endotoxin in mice. Phytomedicine, 18, 1276-1284.
- Katopodis N, Stock CC (1980): Improved method to determine lipid bound sialic acid in plasma or serum. Res Commun Chem Pathol Pharmacol, 30, 171-180.
- Kraft K (1997): Artichoke leaf extract - Recent findings reflecting effects on lipid metabolism, liver and gastrointestinal tracts. Phytomedicine, 4, 369-378.
- Küçükkurt I, Ince S, Keleş H, et al (2010): Beneficial effects of Aesculus hippocastanum L. seed extract on the body’s own antioxidant defense system on subacute administration. J Ethnopharmacol, 129, 18-22.
- Legrand M, Bezemer R, Kandil A, et al (2011): The role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats. Intensive Care Med, 37, 1534-1542.
- Madrigal-Santillán E, Madrigal-Bujaidar E, Álvarez-González I, et al (2014): Review of natural products with hepatoprotective effects. World J Gastroenterol, 20, 14787-14804.
- Matsuda H, Li Y, Murakami T, et al (1997): Effects of escinsIa, Ib, IIa, and IIb from horse chestnut, the seeds of Aesculus hippocastanum L., on acute inflammation in animals. Biol Pharm Bull, 20, 1092-1095.
- Mbarki S, Alimi H, Bouzenna H, et al (2017): Phytochemical study and protective effect of Trigonella foenum graecum (Fenugreek seeds) against carbon tetrachloride-induced toxicity in liver and kidney of male rat. Biomed Pharmacother, 88, 19-26.
- Mehmetçik G, Ozdemirler G, Koçak-Toker N, et al (2008): Effect of pretreatment with artichoke extract on carbon tetrachloride-induced liver injury and oxidative stress. Exp Toxicol Pathol, 60, 475-480.
- Mohan GK, Pallavi E, Kumar R, et al (2007): Hepatoprotective activity of Ficus carica Linn leaf extract against carbon tetrachloride-induced hepatotoxicity in rats. DARU Journal of Pharmaceutical Sciences, 15, 162-166.
- Mujeeb M, Alam Khan S, Aeri V, et al (2011): Hepatoprotective activity of the ethanolic extract of Ficus carica Linn. leaves in carbon tetrachloride-induced hepatotoxicityin rats. Iran J Pharm Res, 10, 301-306.
- Muriel P (2007): Some experimental models of liver damage. S. Sahu (Ed.), Hepatotoxicity: from genomics to in vitro and in vivo models. John Wiley and Sons LTD, West Sussex, UK p. 119-137.
- Nasef MA, Yousef MI, Ghareeb DA, et al (2023): Hepatoprotective effects of a chemically-characterized extract from artichoke (Cynara scolymus L.) against AFB1-induced toxicity in rats. Drug and Chemical Toxicology, 46, 1070-1082.
- Nawaz H, Rehman T, Shahzad H, et al (2024): Hepatoprotective activity of fruit and leaf extracts of Ficus carica and Ficus benghalensis in experimental rats. JAPS, 34, 168-176.
- Ohkawa H, Ohishi N, Yagi K (1979): Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem, 95, 351-358.
- Oliveira I, Sousa A, Ferreira IC, et al (2008): Total phenols, antioxidant potential and antimicrobial activity of walnut (Juglans regia L.) green husks. Food Chem Toxicol, 46, 2326-2331.
- Özkan EE, Mesut B, Polat A, et al (2016): In vitro skin permeation of escin in the new gel formulation of Aesculus hippocastanum (Horse Chestnut). Journal of Faculty of Pharmacy of Istanbul University, 46, 79-88.
- Paglia DE, Valentine WN (1967): Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med, 70, 158-169.
- Parveen R, Baboota S, Ali J, et al (2011): Effects of silymarin nanoemulsion against carbon tetrachloride-induced hepatic damage. Arch Pharm Res, N34, 767-774.
- Peng W, Zhang C, Lv H, et al (2010): Comparative evaluation of the protective potentials of human paraoxonase 1 and 3 against CCl4-induced liver injury. Toxicol Lett, 193, 159-166.
- Pèrez C, Canal JR, Torres MD, et al (2003): Experimental diabetes treated with Ficus carica extract: effect on oxidative stress parameters. Acta Diabetol, 40, 3-8.
- Pérez C, Domínguez E, Canal JR, et al (2000): Hypoglycaemic activity of an aqueous extract from Ficus carica (fig tree) leaves in streptozotocin diabetic rats. Pharm Biol, 38, 181-186.
- Pittler MH, Ernst E (1998): Horse-chestnut seed extract for chronic venous insufficiency, a criteria-based systematic review. Arch Dermatol, 134, 1356-1360.
- Rainone F (2005): Milk thistle. Am Fam Physician, 72, 1285-1288.
- Shaker E, Mahmoud H, Mnaa S (2010): Silymarin, the antioxidant component and Silybum marianum extracts prevent liver damage. Food Chem Toxicol, 48, 803-806.
- Singab AN, Ayoub NA, Ali EN, et al (2010): Antioxidant and hepatoprotective activities of Egyptian moraceous plants against carbon tetrachloride-induced oxidative stress and liver damage in rats. Pharm Biol, 48, 1255-1264.
- Singh H, Sidhu S, Chopra K, et al (2017): The novel role of β-aescin in attenuating CCl4-induced hepatotoxicity in rats. Pharm Bio, 55, 749-757.
- Sirtori CR (2001): Aescin: pharmacology, pharmacokinetics and therapeutic profile. Pharmacol Res, 44, 183-193.
- Stampar F, Solar A, Hudina M, et al (2006): Traditional walnut liqueur–cocktail of phenolics. Food Chemistry, 95, 627-631.
- Tacke F, Luedde T, Trautwein C (2009): Inflammatory pathways in liver homeostasis and liver injury. Clin Rev Allergy Immunol, 36, 4-12.
- Wellington K, Jarvis B (2001): Silymarin: a review of its clinical properties in the management of hepatic disorders. BioDrugs, 15, 465-489.
- Winterbourn CC, Hawkins RE, Brian M, et al (1975): The estimation of red cell superoxide dismutase activity. J Lab Clin Med, 85, 337-341.
- Yang CC, Fang JY, Hong TL, et al (2013): Potential antioxidant properties and hepatoprotective effects of an aqueous extract formula derived from three Chinese medicinal herbs against CCl(4)-induced liver injury in rats. Int Immunopharmacol, 15, 106-113.
- Yassin NYS, AbouZid SF, El-Kalaawy AM, et al (2022): Silybum marianum total extract, silymarin and silibinin abate hepatocarcinogenesis and hepatocellular carcinoma growth via modulation of the HGF/c-Met, Wnt/β-catenin, and PI3K/Akt/mTOR signaling pathways. Biomed Pharmacother, 145, 112409.
- Zhang DG, Zhang C, Wang JX, et al (2017): Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation. Toxicol Appl Pharmacol, 314, 39-47.
- Zhang R, Hu Y, Yuan J, et al (2009): Effects of Puerariae radix extract on the increasing intestinal permeability in rat with alcohol-induced liver injury. J Ethnopharmacol, 126, 207-214.
- Zhu X, Zhang H, Lo R, et al (2005): Antimicrobial activities of Cynara scolymus L. leaf, head, and stem extracts. Journal of Food Science, 70, M149-M152.
Year 2025,
Volume: 72 Issue: 1, 47 - 57
Asli Kandil
,
Aysu Kılıc
,
Ebru Gürel Gürevin
,
İbrahim Söğüt
,
Savaş Üstünova
,
Şeyma Eren
,
Metin Caner
,
Cihan Demirci Tansel
References
- Abenavoli L, Capasso R, Milic N, et al (2010): Milk thistle in liver diseases: past, present, future. Phytother Res, 24, 1423-1432.
- Abenavoli L, Izzo AA, Milić N, et al (2018): Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Phytother Res, 32, 2202-2213.
- Aghel N, Kalantari H, Rezazadeh S (2011): Hepatoprotective effect of Ficus carica leaf extract on mice intoxicated with carbon tetrachloride. Iran J Pharm Res, 10, 63-68.
- Ali B, Mujeeb M, Aeri V, et al (2012): Anti-inflammatory and antioxidant activity of Ficus carica Linn. Leaves. Nat Prod Res, 26, 460-465.
- Al-Olayan EM, El-Khadragy MF, Aref AM, et al (2014): The potential protective effect of Physalis peruviana L. against carbon tetrachloride-induced hepatotoxicity in rats is mediated by suppression of oxidative stress and downregulation of MMP-9 expression. Oxid Med Cell Longev, 2014, 381413.
- Al-Rasheed N, Faddah L, Al-Rasheed N, et al (2016): Protective effects of silymarin, alone or in combination with chlorogenic acid and/or melatonin, against carbon tetrachloride-induced hepatotoxicity. Pharmacogn Mag, 12, S337-S345.
- Alshatwi AA, Hasan TN, Shafi G, et al (2012): Validation of the antiproliferative effects of organic extracts from the green husk of Juglans regia L. on PC-3 human prostate cancer cells by assessment of apoptosis-related genes. Evid Based Complement Alternat Med, 2012, 103026.
- Aslan A, Can MI (2014): Milk thistle impedes the development of carbontetrachloride-induced liver damage in rats through suppression of bcl-2 and regulating caspase pathway. Life Sci, 117, 13-18.
- Aydın S, Gökçe Z, Yılmaz Ö (2015): The effects of Juglans regia L. (walnut) extract on certain biochemical paramaters and in the prevention of tissue damage in brain, kidney, and liver in CCl4 applied Wistar rats. Turk J Biochem, 40, 241-250.
- Beutler E (1982): Red cell metabolism: A manual of biochemical methods. 3rd edition. Grune and Stratton; New York.
- Bradford MM (1976): A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem, 72, 248-254.
- Clawson GA (1989): Mechanisms of carbon tetrachloride hepatotoxicity. Pathol Immunopathol Res, 8, 104-112.
- Colak E, Ustuner MC, Tekin N, et al (2016): The hepatocurative effects of Cynara scolymus L. leaf extract on carbon tetrachloride-induced oxidative stress and hepatic injury in rats. Springerplus, 5, 216.
- De La Puerta R, Martinez E, Bravo L, et al (1996): Effect of silymarin on different acute inflammation models and on leukocyte migration. J Pharm Pharmacol, 48, 968-670.
- Demirci C, Gargili A, Kandil A, et al (2006): Inhibition of inducible nitric oxide synthase in murine visceral larva migrans: effects on lung and liver damage. Chin J Physiol, 49, 326-334.
- Donga D, Xua L, Yina L, et al (2015): Naringin prevents carbon tetrachloride-induced acute liver injury in mice. J Funct Foods, 12, 179-191.
- Eassawy MMT, Ismail AFM (2024): Protective effect of chicory and/or artichoke leaves extracts on carbon tetrachloride and gamma-irradiation-induced chronic nephrotoxicity in rats. Environmental Toxicology, 39, 1666-1681.
- Eidi A, Moghadam JZ, Mortazavi P, et al (2013): Hepatoprotective effects of Juglans regia extract against CCl4-induced oxidative damage in rats. Pharm Biol, 51, 558-565.
- El-Boshy M, Ashshi A, Gaith M, et al (2017): Studies on the protective effect of the artichoke (Cynara scolymus) leaf extract against cadmium toxicity-induced oxidative stress, hepatorenal damage, and immunosuppressive and hematological disorders in rats. Environ Sci Pollut Res Int, 24, 12372-12383.
- Elmas O, Erbas O, Yigitturk G (2016): The efficacy of Aesculus hippocastanum seeds on diabetic nephropathy in a streptozotocin-induced diabetic rat model. Biomed Pharmacother, 83, 392-396.
- Florek E, Szukalska M, Markiewicz K, et al (2023): Evaluation of the protective and regenerative properties of commercially available artichoke leaf powder extract on plasma and liver oxidative stress parameters. Antioxidants (Basel), 12, 1846.
- Gebhardt R (1997): Antioxidative and protective properties of extracts from leaves of the artichoke (Cynara scolymus L.) against hydroperoxide-induced oxidative stress in cultured rat hepatocytes. Toxicol Appl Pharmacol, 144, 279-286.
- Guarrera PM (2005): Traditional phytotherapy in Central Italy (Marche, Abruzzo, and Latium). Fitoterapia, 76, 1-25.
- Gurel E, Ustunova S, Ergin B, et al (2013): Herbal haemorrhoidal cream for haemorrhoids. Chin J Physiol, 56, 253-262.
- Haque R, Bin-Hafeez B, Parvez S, et al (2003): Aqueous extract of walnut (Juglans regia L.) protects mice against cyclophosphamide-induced biochemical toxicity. Hum Exp Toxicol, 22, 473-480.
- Hosseini SA, Mohammadi J, Delaviz H, et al (2018): Effect of Juglans regia and Nasturtum officinalis biochemical parameters following toxicity of kidney by CCl4 in Wistar rats. Electronic Journal of General Medicine, 15.
- Jiang G, Sun C, Wang X, et al (2022): Hepatoprotective mechanism of Silybum marianum on nonalcoholic fatty liver disease based on network pharmacology and experimental verification. Bioengineered, 13, 5216-5235.
- Jiang N, Xin W, Wang T, et al (2011): Protective effect of aescin from the seeds of Aesculus hippocastanum on liver injury induced by endotoxin in mice. Phytomedicine, 18, 1276-1284.
- Katopodis N, Stock CC (1980): Improved method to determine lipid bound sialic acid in plasma or serum. Res Commun Chem Pathol Pharmacol, 30, 171-180.
- Kraft K (1997): Artichoke leaf extract - Recent findings reflecting effects on lipid metabolism, liver and gastrointestinal tracts. Phytomedicine, 4, 369-378.
- Küçükkurt I, Ince S, Keleş H, et al (2010): Beneficial effects of Aesculus hippocastanum L. seed extract on the body’s own antioxidant defense system on subacute administration. J Ethnopharmacol, 129, 18-22.
- Legrand M, Bezemer R, Kandil A, et al (2011): The role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats. Intensive Care Med, 37, 1534-1542.
- Madrigal-Santillán E, Madrigal-Bujaidar E, Álvarez-González I, et al (2014): Review of natural products with hepatoprotective effects. World J Gastroenterol, 20, 14787-14804.
- Matsuda H, Li Y, Murakami T, et al (1997): Effects of escinsIa, Ib, IIa, and IIb from horse chestnut, the seeds of Aesculus hippocastanum L., on acute inflammation in animals. Biol Pharm Bull, 20, 1092-1095.
- Mbarki S, Alimi H, Bouzenna H, et al (2017): Phytochemical study and protective effect of Trigonella foenum graecum (Fenugreek seeds) against carbon tetrachloride-induced toxicity in liver and kidney of male rat. Biomed Pharmacother, 88, 19-26.
- Mehmetçik G, Ozdemirler G, Koçak-Toker N, et al (2008): Effect of pretreatment with artichoke extract on carbon tetrachloride-induced liver injury and oxidative stress. Exp Toxicol Pathol, 60, 475-480.
- Mohan GK, Pallavi E, Kumar R, et al (2007): Hepatoprotective activity of Ficus carica Linn leaf extract against carbon tetrachloride-induced hepatotoxicity in rats. DARU Journal of Pharmaceutical Sciences, 15, 162-166.
- Mujeeb M, Alam Khan S, Aeri V, et al (2011): Hepatoprotective activity of the ethanolic extract of Ficus carica Linn. leaves in carbon tetrachloride-induced hepatotoxicityin rats. Iran J Pharm Res, 10, 301-306.
- Muriel P (2007): Some experimental models of liver damage. S. Sahu (Ed.), Hepatotoxicity: from genomics to in vitro and in vivo models. John Wiley and Sons LTD, West Sussex, UK p. 119-137.
- Nasef MA, Yousef MI, Ghareeb DA, et al (2023): Hepatoprotective effects of a chemically-characterized extract from artichoke (Cynara scolymus L.) against AFB1-induced toxicity in rats. Drug and Chemical Toxicology, 46, 1070-1082.
- Nawaz H, Rehman T, Shahzad H, et al (2024): Hepatoprotective activity of fruit and leaf extracts of Ficus carica and Ficus benghalensis in experimental rats. JAPS, 34, 168-176.
- Ohkawa H, Ohishi N, Yagi K (1979): Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem, 95, 351-358.
- Oliveira I, Sousa A, Ferreira IC, et al (2008): Total phenols, antioxidant potential and antimicrobial activity of walnut (Juglans regia L.) green husks. Food Chem Toxicol, 46, 2326-2331.
- Özkan EE, Mesut B, Polat A, et al (2016): In vitro skin permeation of escin in the new gel formulation of Aesculus hippocastanum (Horse Chestnut). Journal of Faculty of Pharmacy of Istanbul University, 46, 79-88.
- Paglia DE, Valentine WN (1967): Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med, 70, 158-169.
- Parveen R, Baboota S, Ali J, et al (2011): Effects of silymarin nanoemulsion against carbon tetrachloride-induced hepatic damage. Arch Pharm Res, N34, 767-774.
- Peng W, Zhang C, Lv H, et al (2010): Comparative evaluation of the protective potentials of human paraoxonase 1 and 3 against CCl4-induced liver injury. Toxicol Lett, 193, 159-166.
- Pèrez C, Canal JR, Torres MD, et al (2003): Experimental diabetes treated with Ficus carica extract: effect on oxidative stress parameters. Acta Diabetol, 40, 3-8.
- Pérez C, Domínguez E, Canal JR, et al (2000): Hypoglycaemic activity of an aqueous extract from Ficus carica (fig tree) leaves in streptozotocin diabetic rats. Pharm Biol, 38, 181-186.
- Pittler MH, Ernst E (1998): Horse-chestnut seed extract for chronic venous insufficiency, a criteria-based systematic review. Arch Dermatol, 134, 1356-1360.
- Rainone F (2005): Milk thistle. Am Fam Physician, 72, 1285-1288.
- Shaker E, Mahmoud H, Mnaa S (2010): Silymarin, the antioxidant component and Silybum marianum extracts prevent liver damage. Food Chem Toxicol, 48, 803-806.
- Singab AN, Ayoub NA, Ali EN, et al (2010): Antioxidant and hepatoprotective activities of Egyptian moraceous plants against carbon tetrachloride-induced oxidative stress and liver damage in rats. Pharm Biol, 48, 1255-1264.
- Singh H, Sidhu S, Chopra K, et al (2017): The novel role of β-aescin in attenuating CCl4-induced hepatotoxicity in rats. Pharm Bio, 55, 749-757.
- Sirtori CR (2001): Aescin: pharmacology, pharmacokinetics and therapeutic profile. Pharmacol Res, 44, 183-193.
- Stampar F, Solar A, Hudina M, et al (2006): Traditional walnut liqueur–cocktail of phenolics. Food Chemistry, 95, 627-631.
- Tacke F, Luedde T, Trautwein C (2009): Inflammatory pathways in liver homeostasis and liver injury. Clin Rev Allergy Immunol, 36, 4-12.
- Wellington K, Jarvis B (2001): Silymarin: a review of its clinical properties in the management of hepatic disorders. BioDrugs, 15, 465-489.
- Winterbourn CC, Hawkins RE, Brian M, et al (1975): The estimation of red cell superoxide dismutase activity. J Lab Clin Med, 85, 337-341.
- Yang CC, Fang JY, Hong TL, et al (2013): Potential antioxidant properties and hepatoprotective effects of an aqueous extract formula derived from three Chinese medicinal herbs against CCl(4)-induced liver injury in rats. Int Immunopharmacol, 15, 106-113.
- Yassin NYS, AbouZid SF, El-Kalaawy AM, et al (2022): Silybum marianum total extract, silymarin and silibinin abate hepatocarcinogenesis and hepatocellular carcinoma growth via modulation of the HGF/c-Met, Wnt/β-catenin, and PI3K/Akt/mTOR signaling pathways. Biomed Pharmacother, 145, 112409.
- Zhang DG, Zhang C, Wang JX, et al (2017): Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation. Toxicol Appl Pharmacol, 314, 39-47.
- Zhang R, Hu Y, Yuan J, et al (2009): Effects of Puerariae radix extract on the increasing intestinal permeability in rat with alcohol-induced liver injury. J Ethnopharmacol, 126, 207-214.
- Zhu X, Zhang H, Lo R, et al (2005): Antimicrobial activities of Cynara scolymus L. leaf, head, and stem extracts. Journal of Food Science, 70, M149-M152.