Hepatoprotective properties for Salvia cryptantha extract on carbon tetrachloride-induced liver injury

Alper Yalcin; Onder Yumrutas; Tuncay Kuloglu; Ebru Elibol; Ali Parlar; ć°smet Yilmaz; Mustafa Pehlivan; Mevlut Dogukan; Fatih Uckardes; Hasan Aydin; Ahmet Turk; Oznur Uludag; ć°brahim Sahin; Kader Ugur; Suleyman Aydin

doi:10.14715/10.14715/cmb/2017.63.12.13

Issue

Vol. 63 No. 12: Issue 12

Issue Published : December 19, 2017

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Hepatoprotective properties for Salvia cryptantha extract on carbon tetrachloride-induced liver injury

https://doi.org/10.14715/10.14715/cmb/2017.63.12.13

Alper Yalcin

Department of Histology and Embryology, Faculty of Medicine, Adiyaman University, Adiyaman, Turkey

Onder Yumrutas

Department of Medical Biology, Faculty of Medicine, Adiyaman University, Adiyaman,Turkey

Tuncay Kuloglu

Department of Histology and Embryology, Faculty of Medicine, Firat University, Elazig,Turkey

Ebru Elibol

Department of Histology and Embryology, Faculty of Medicine, Adiyaman University, Adiyaman, Turkey

Ali Parlar

Department of Pharmacology, Faculty of Pharmacy, Adiyaman University Malatya,Turkey

ć°smet Yilmaz

Department of Pharmacology, Faculty of Pharmacy, Inonu University, Malatya,Turkey

Mustafa Pehlivan

Department of Medical and Aromatic Plants, Nurdagi Vocational Higher School, Gaziantep University, Gaziantep,Turkey

Mevlut Dogukan

Department of Anesthesiology and Reanimation, Faculty of Medicine, Adiyaman University, Adiyaman,Turkey

Fatih Uckardes

Department of Biostatistics and Medical Informatics, Faculty of Medicine, Adiyaman University, Adiyaman,Turkey

Hasan Aydin

Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Adiyaman University, Adiyaman,Turkey

Ahmet Turk

Department of Histology and Embryology, Faculty of Medicine, Adiyaman University, Adiyaman, Turkey

Oznur Uludag

Department of Anesthesiology and Reanimation, Faculty of Medicine, Adiyaman University, Adiyaman,Turkey

ć°brahim Sahin

Department of Medical Biochemistry (Firat Hormones Research Group), Faculty of Medicine, Firat University, Elazig,Turkey

Kader Ugur

Department of Internal Medicine, Faculty of Medicine, Firat University, Elazig,Turkey

Suleyman Aydin

Department of Medical Biochemistry (Firat Hormones Research Group), Faculty of Medicine, Firat University, Elazig,Turkey

Corresponding Author(s) : Suleyman Aydin

saydin1@hotmail.com

Cellular and Molecular Biology, Vol. 63 No. 12: Issue 12
Article Published : December 30, 2017

Abstract

The present study was designed to determine the possible hepatoprotective effects of Salvia cryptantha (black weed) plant extract against carbon tetrachloride (CCl4)-induced hepatic injury in rats. Animals were grouped as follows: control group (Group I), CCl4 group (Group II), olive oil group (Group III), CCl4 + S. cryphantha 200 mg/kg group (Group IV), and CCl4 + S. cryptantha 400mg/kg group (Group V). Rats were injected intraperitoneally with CCl4 diluted in olive oil (50% v/v) at a dose of 1ml/kg body weight. Bax and Caspase3 were determined by immunohistochemical staining, while apoptotic index was evaluated using TUNEL assay. Total mRNA was isolated from liver tissues, and the levels of BCL2, Caspase3, SOD, CAT, and glutathione peroxidase (GPx) were determined by using PCR, while MDA level were determined using a colorimetric assay. The antioxidant and anti-apoptotic gene transcripts were decreased in all of the control and treatment groups, while Caspase3 levels were not statistically different. The S. cryptantha plant extract treatment was also found to improve SOD, GPx, and catalase levels, while reducing the serum levels of MDA. The extract of S. cryptantha supplementation had a protective effect against CCl4-induced liver damage. S. cryptantha extract as a supplement may be useful as a hepato-protective agent to combat the toxic effects caused by CCl4 and other chemicals.

Keywords

Carbon tetrachloride TUNEL Caspase3 BCL2 Liver injury Salvia cryptantha.

Yalcin, A., Yumrutas, O., Kuloglu, T., Elibol, E., Parlar, A., Yilmaz, ć°smet, Pehlivan, M., Dogukan, M., Uckardes, F., Aydin, H., Turk, A., Uludag, O., Sahin, ć°brahim, Ugur, K., & Aydin, S. (2017). Hepatoprotective properties for Salvia cryptantha extract on carbon tetrachloride-induced liver injury. Cellular and Molecular Biology, 63(12), 56–62. https://doi.org/10.14715/10.14715/cmb/2017.63.12.13

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References

Burroughs AK, Westaby D. Liver, Biliary tract and pancreatic disease. In: Kumar P, Clarke ML, (Eds.) Clinical Medicine. 6th ed. New York: Elsevier Saunders; 2005, p. 347-418.
Jaurigue MM, Cappell MS. Therapy for alcoholic liver disease. World J Gastroenterol 2014; 20:2143-58.
Britton LJ, Subramaniam VN, Crawford DH. Iron and non-alcoholic fatty liver disease. World J Gastroenterol 2016; 22:8112-8122.
Saracco GM, Evangelista A, Fagoonee S, Ciccone G, Bugianesi E, Caviglia GP, et al. Etiology of chronic liver diseases in the Northwest of Italy, 1998 through 2014. World J Gastroenterol 2016; 22:8187-93.
Martinez-Perez A, Alberola-Soler A, Domingo-del Pozo C, Pemartin-Comella B, Martinez-Lopez E, Vazquez-Tarragon A. Laparoscopic surgery and polycystic liver disease: Clinicopathological features and new trends in management. J Minim Access Surg 2016; 12:265-73.
Ma JQ, Ding J, Zhang L, Liu CM. Hepatoprotective properties of sesamin against CCl4 induced oxidative stress-mediated apoptosis in mice via JNK pathway. Food Chem Toxicol 2014; 64:41-48.
Obermayer-Straub PETRA, Manns MP, Immunological mechanisms in liver injury. In: Kaplowitz N, DeLeve L, (Eds.) Drug-Induced Liver Disease. New York: Marcel Dekker; 2003, p. 145-149.
Kerr JFR, Winterfold CM. Apoptosis its significance in Cancer and Cancer Therapy. Cancer 1994; 73:2013-26.
Duval F, Moreno-Cuevas JE, González-Garza MT, Rodríguez-Montalvo C, Cruz-Vega DE. Liver fibrosis and protection mechanisms action of medicinal plants targeting apoptosis of hepatocytes and hepatic stellate cells. Adv Pharmacol Sci 2014; 2014:373295.
Tepe B, Sokmen M, Akpulat HA, Sokmen A. Screening of the antioxidant potentials of six Salvia species from Turkey. Food Chem 2006; 95:200-4.
Yumrutas O, Sokmen A, Akpulat HA, Ozturk N, Daferera D, Sokmen M, et al. Phenolic acid contents, essential oil compositions and antioxidant activities of two varieties of Salvia euphratica from Turkey. Nat Prod Res 2012; 26:1848-51.
Yumrutas O, Oztuzcu S, Pehlivan M, Ozturk N, Poyraz IE, Iğci YZ, et al. Cell viability, anti-proliferation and antioxidant activities of Sideritis syriaca, Tanacetum argenteum sub sp. argenteum and Achillea aleppica subsp. zederbaueri on human breast cancer cell line (MCF-7). J App Pharm Sci 2015; 5:001-5.
Morisco F, Vitaglione P, Amoruso D, Russo B, Fogliano V, Caporaso N. Foods and liver health. Mol Aspects Med 2008; 29:144-50.
Akanitapichat P, Phraibung K, Nuchklang K, Prompitakkul S. Antioxidant and hepatoprotective activities of five eggplant varieties. Food Chem Toxicol 2010; 48:3017-21.
Rezaeieh KAP, Shidfar M, Gürbüz B, Khavar KM. Genomic DNA extraction from seed induced callus and explants in Salvia L. species for utilization in secondary metabolite production. J Med Plant Res 2012; 6:636-40.
Davis PH, (Eds) Flora of Turkey and the east aegean Islands. Edinburgh: Edinburgh at the University press; 1982, 431-2.
Tepe B, Sokmen M, Akpulat HA, Yumrutas O, Sokmen A. Screening of antioxidative properties of the methanolic extracts of Pelargonium endlicherianum Fenzl., Verbascum wiedemannianum Fisch. & Mey., Sideritis libanotica Labill. subsp. linearis (Bentham) Borm., Centaurea mucronifera DC. and Hieracium cappadocicum Freyn from Turkish flora. Food Chem 2006; 98:9-13.
Süntar ć°, Akkol EK, Åženol FS, Keles H, Orhan IE. Investigating wound healing, tyrosinase inhibitory and antioxidant activities of the ethanol extracts of Salvia cryptantha and Salvia cyanescens using in vivo and in vitro experimental models. J Ethnopharmacol 2011; 135:71-7.
Utley HG, Bernheim F, Hockstein P. Effect of sulfhydryl reagents on peroxidation in microsomes. Arch Biochem Biophys 1967; 118:29-32.
El-Hosseiny LS, Alqurashy NN, Sheweita SA. Oxidative Stress Alleviation by Sage Essential Oil in Co-amoxiclav induced Hepatotoxicity in Rats. Int J Biomed Sci 2016; 12:71-8.
Wang Y, Wan Y, Ye G, Wang P, Xue X, Wu G, et al. Hepatoprotective effects of AdipoRon against d-galactosamine-induced liver injury in mice. Eur J Pharm Sci 2016; 93:123-31.
Du J, Cao L, Jia R, Yin G. Hepatoprotective and antioxidant effects of dietary Glycyrrhiza polysaccharide against TCDD-induced hepatic injury and RT-PCR quantification of AHR2, ARNT2, CYP1A mRNA in Jian Carp (Cyprinus carpio var. Jian). J Environ Sci (China) 2017; 51:181-90.
Jiang Y, Fan X, Wang Y, Tan H, Chen P, Zeng H, et al. Hepato-protective effects of six schisandra lignans on acetaminophen-induced liver injury are partially associated with the inhibition of CYP-mediated bioactivation. Chem Biol Interact 2015; 231:83-9.
Yadav YC. Hepatoprotective effect of Ficus religiosa latex on cisplatin induced liver injury in Wistar rats. Rev Bras Farmacogn 2015; 25:278-83.
Dey P, Dutta S, Sarkar MP, Chaudhuri TK. Assessment of hepatoprotective potential of N. indicum leaf on haloalkane xenobiotic induced hepatic injury in Swiss albino mice. Chem Biol Interact 2015; 235:37-46.
Sundari K, Karthik D, Ilavenil S, Kaleeswaran B, Srigopalram S, Ravikumar S. Hepatoprotective and proteomic mechanism of Sphaeranthus indicus in paracetamol induced hepatotoxicity in wistar rats. Food Biosci 2013; 1:57-65.
Kus I, Colakoglu N, Pekmez H, Seckin D, Ogeturk M, Sarsilmaz M. Protective effects of caffeic acid phenethyl ester (CAPE) on carbon tetrachloride-induced hepatotoxicity in rats. Acta Histochem 2004; 106:289-97.
Fernandez G, Villarruel MC, De Toranzo EG, Castro JA. Covalent binding of carbon tetrachloride metabolites to the heme moiety of cytochrome P-450 and its degradation products. Res Comm Chem Pathol Pharmacol 1982; 35:283-90.
Vuittonet CL, Halse M, Leggio L, Fricchione SB, Brickley M, Haass-Koffler CL, et al. Pharmacotherapy for alcoholic patients with alcoholic liver disease. Am J Health Syst Pharm 2014; 71:1265-76.
Ghaffari H, Venkataramana M, Nayaka SC, Ghassam BJ, Angaswamy N, Shekar S, et al. Hepatoprotective action of Orthosiphon diffusus (Benth.) methanol active fraction through antioxidant mechanisms: An in vivo and in vitro evaluation. J Ethnopharmacol 2013; 149:737-44.
Ooi KL, Loh SI, Sattar MA, Muhammad TST, Sulaiman SF. Cytotoxic, caspase-3 induction and in vivo hepatoprotective effects of phyllanthin, a major constituent of Phyllanthus niruri. J Funct Foods 2015; 14:236-43.
Ansar S, Siddiqi NJ, Zargar S, Ganaie MA, Abudawood M. Hepatoprotective effect of Quercetin supplementation against Acrylamide-induced DNA damage in wistar rats. BMC Complement Altern Med 2016; 16:327.
Kandimalla R, Dash S, Kalita S, Choudhury B, Malampati S, Kalita K, et al. Bioactive guided fractions of Annona reticulata L. bark: protection against liver toxicity and inflammation through inhibiting oxidative stress and proinflammatory cytokines. Front Pharmacol 2016; 7:168.
Lee TY, Mai LM, Wang GJ, Chiu JH, Lin YL, Lin HC. Protective mechanism of salvia miltiorrhiza on carbon tetrachloride-induced acute hepatotoxicity in rats. J Pharmacol Sci 2003; 91:202-10.
Banna H, SolimanM., Wabel N. Hepatoprotective effects of Thymus and Salvia essential oils on paracetamol-induced toxicity in rats. J Essent Oil Res 2013; 3:41-7.
Xavier CP, Pereira-Wilson C. Medicinal plants of the genuses Salvia and Hypericum are sources of anticolon cancer compounds: Effects on PI3K/Akt and MAP kinases pathways. Pharma Nutrition 2016; 4:112-22.
Zhou R, He LF, Li YJ, Shen Y, Chao RB, Du JR. Cardioprotective effect of water and ethanol extract of Salvia miltiorrhiza in an experimental model of myocardial infarction. J Ethnopharmacol 2012; 139:440-6.
Porres-Martínez M, González-Burgos E, Carretero ME, Gómez-Serranillos MP. Protective properties of Salvia lavandulifolia Vahl. essential oil against oxidative stress-induced neuronal injury. Food Chem Toxicol 2015; 80:154-62.
Choi JK, Oh HM, Park JH, Choi JH, Sa KH, Kang YM, et al. Salvia plebeia extract inhibits the inflammatory response in human rheumatoid synovial fibroblasts and a murine model of arthritis. Phytomedicine 2015; 22:415-22.
Baser KHC, Beis SH, í–zek T. Composition of the essential oil of Salvia cryptantha Montbret et Aucher ex Benth. from Turkey. J Essent Oil Res 1995; 7:113-4.
Ulubelen A, Topcu G, Terem B. Abietna diterpenoids from the roots of Salvia cryptantha. Phytochem 1987; 26:1534-5.
Bold RJ, Termuhlen PM, McConkey DJ. Apoptosis, cancer and cancer therapy. Surg Oncol 1997; 6:133-42.
Shi J, Aisaki K, Ikawa Y, Wake K. Evidence of hepatocyte apoptosis in rat liver after the administration of carbon tetrachloride. Am J Pathol 1998; 153:515-25.
Yasuda M, Okabe T, Itoh J, Takekoshi S, Hasegawa H Nagata, H, et al. Differentiation of necrotic cell death with or without lysosomal activation: application of acute liver injury models induced by carbon tetrachloride (CCl4) and dimethylnitrosamine (DMN). J Histochem Cytochem 2000; 48:1331-9.
Jin Q, Jiang S, Wu YL, Bai T, Yang Y, Jin X, et al. Hepatoprotective effect of cryptotanshinone from Salvia miltiorrhiza in D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure. Phytomedicine 2014; 21:141-7.

References

Burroughs AK, Westaby D. Liver, Biliary tract and pancreatic disease. In: Kumar P, Clarke ML, (Eds.) Clinical Medicine. 6th ed. New York: Elsevier Saunders; 2005, p. 347-418.

Jaurigue MM, Cappell MS. Therapy for alcoholic liver disease. World J Gastroenterol 2014; 20:2143-58.

Britton LJ, Subramaniam VN, Crawford DH. Iron and non-alcoholic fatty liver disease. World J Gastroenterol 2016; 22:8112-8122.

Saracco GM, Evangelista A, Fagoonee S, Ciccone G, Bugianesi E, Caviglia GP, et al. Etiology of chronic liver diseases in the Northwest of Italy, 1998 through 2014. World J Gastroenterol 2016; 22:8187-93.

Martinez-Perez A, Alberola-Soler A, Domingo-del Pozo C, Pemartin-Comella B, Martinez-Lopez E, Vazquez-Tarragon A. Laparoscopic surgery and polycystic liver disease: Clinicopathological features and new trends in management. J Minim Access Surg 2016; 12:265-73.

Ma JQ, Ding J, Zhang L, Liu CM. Hepatoprotective properties of sesamin against CCl4 induced oxidative stress-mediated apoptosis in mice via JNK pathway. Food Chem Toxicol 2014; 64:41-48.

Obermayer-Straub PETRA, Manns MP, Immunological mechanisms in liver injury. In: Kaplowitz N, DeLeve L, (Eds.) Drug-Induced Liver Disease. New York: Marcel Dekker; 2003, p. 145-149.

Kerr JFR, Winterfold CM. Apoptosis its significance in Cancer and Cancer Therapy. Cancer 1994; 73:2013-26.

Duval F, Moreno-Cuevas JE, González-Garza MT, Rodríguez-Montalvo C, Cruz-Vega DE. Liver fibrosis and protection mechanisms action of medicinal plants targeting apoptosis of hepatocytes and hepatic stellate cells. Adv Pharmacol Sci 2014; 2014:373295.

Tepe B, Sokmen M, Akpulat HA, Sokmen A. Screening of the antioxidant potentials of six Salvia species from Turkey. Food Chem 2006; 95:200-4.

Yumrutas O, Sokmen A, Akpulat HA, Ozturk N, Daferera D, Sokmen M, et al. Phenolic acid contents, essential oil compositions and antioxidant activities of two varieties of Salvia euphratica from Turkey. Nat Prod Res 2012; 26:1848-51.

Yumrutas O, Oztuzcu S, Pehlivan M, Ozturk N, Poyraz IE, Iğci YZ, et al. Cell viability, anti-proliferation and antioxidant activities of Sideritis syriaca, Tanacetum argenteum sub sp. argenteum and Achillea aleppica subsp. zederbaueri on human breast cancer cell line (MCF-7). J App Pharm Sci 2015; 5:001-5.

Morisco F, Vitaglione P, Amoruso D, Russo B, Fogliano V, Caporaso N. Foods and liver health. Mol Aspects Med 2008; 29:144-50.

Akanitapichat P, Phraibung K, Nuchklang K, Prompitakkul S. Antioxidant and hepatoprotective activities of five eggplant varieties. Food Chem Toxicol 2010; 48:3017-21.

Rezaeieh KAP, Shidfar M, Gürbüz B, Khavar KM. Genomic DNA extraction from seed induced callus and explants in Salvia L. species for utilization in secondary metabolite production. J Med Plant Res 2012; 6:636-40.

Davis PH, (Eds) Flora of Turkey and the east aegean Islands. Edinburgh: Edinburgh at the University press; 1982, 431-2.

Tepe B, Sokmen M, Akpulat HA, Yumrutas O, Sokmen A. Screening of antioxidative properties of the methanolic extracts of Pelargonium endlicherianum Fenzl., Verbascum wiedemannianum Fisch. & Mey., Sideritis libanotica Labill. subsp. linearis (Bentham) Borm., Centaurea mucronifera DC. and Hieracium cappadocicum Freyn from Turkish flora. Food Chem 2006; 98:9-13.

Süntar ć°, Akkol EK, Åženol FS, Keles H, Orhan IE. Investigating wound healing, tyrosinase inhibitory and antioxidant activities of the ethanol extracts of Salvia cryptantha and Salvia cyanescens using in vivo and in vitro experimental models. J Ethnopharmacol 2011; 135:71-7.

Utley HG, Bernheim F, Hockstein P. Effect of sulfhydryl reagents on peroxidation in microsomes. Arch Biochem Biophys 1967; 118:29-32.

El-Hosseiny LS, Alqurashy NN, Sheweita SA. Oxidative Stress Alleviation by Sage Essential Oil in Co-amoxiclav induced Hepatotoxicity in Rats. Int J Biomed Sci 2016; 12:71-8.

Wang Y, Wan Y, Ye G, Wang P, Xue X, Wu G, et al. Hepatoprotective effects of AdipoRon against d-galactosamine-induced liver injury in mice. Eur J Pharm Sci 2016; 93:123-31.

Du J, Cao L, Jia R, Yin G. Hepatoprotective and antioxidant effects of dietary Glycyrrhiza polysaccharide against TCDD-induced hepatic injury and RT-PCR quantification of AHR2, ARNT2, CYP1A mRNA in Jian Carp (Cyprinus carpio var. Jian). J Environ Sci (China) 2017; 51:181-90.

Jiang Y, Fan X, Wang Y, Tan H, Chen P, Zeng H, et al. Hepato-protective effects of six schisandra lignans on acetaminophen-induced liver injury are partially associated with the inhibition of CYP-mediated bioactivation. Chem Biol Interact 2015; 231:83-9.

Yadav YC. Hepatoprotective effect of Ficus religiosa latex on cisplatin induced liver injury in Wistar rats. Rev Bras Farmacogn 2015; 25:278-83.

Dey P, Dutta S, Sarkar MP, Chaudhuri TK. Assessment of hepatoprotective potential of N. indicum leaf on haloalkane xenobiotic induced hepatic injury in Swiss albino mice. Chem Biol Interact 2015; 235:37-46.

Sundari K, Karthik D, Ilavenil S, Kaleeswaran B, Srigopalram S, Ravikumar S. Hepatoprotective and proteomic mechanism of Sphaeranthus indicus in paracetamol induced hepatotoxicity in wistar rats. Food Biosci 2013; 1:57-65.

Kus I, Colakoglu N, Pekmez H, Seckin D, Ogeturk M, Sarsilmaz M. Protective effects of caffeic acid phenethyl ester (CAPE) on carbon tetrachloride-induced hepatotoxicity in rats. Acta Histochem 2004; 106:289-97.

Fernandez G, Villarruel MC, De Toranzo EG, Castro JA. Covalent binding of carbon tetrachloride metabolites to the heme moiety of cytochrome P-450 and its degradation products. Res Comm Chem Pathol Pharmacol 1982; 35:283-90.

Vuittonet CL, Halse M, Leggio L, Fricchione SB, Brickley M, Haass-Koffler CL, et al. Pharmacotherapy for alcoholic patients with alcoholic liver disease. Am J Health Syst Pharm 2014; 71:1265-76.

Ghaffari H, Venkataramana M, Nayaka SC, Ghassam BJ, Angaswamy N, Shekar S, et al. Hepatoprotective action of Orthosiphon diffusus (Benth.) methanol active fraction through antioxidant mechanisms: An in vivo and in vitro evaluation. J Ethnopharmacol 2013; 149:737-44.

Ooi KL, Loh SI, Sattar MA, Muhammad TST, Sulaiman SF. Cytotoxic, caspase-3 induction and in vivo hepatoprotective effects of phyllanthin, a major constituent of Phyllanthus niruri. J Funct Foods 2015; 14:236-43.

Ansar S, Siddiqi NJ, Zargar S, Ganaie MA, Abudawood M. Hepatoprotective effect of Quercetin supplementation against Acrylamide-induced DNA damage in wistar rats. BMC Complement Altern Med 2016; 16:327.

Kandimalla R, Dash S, Kalita S, Choudhury B, Malampati S, Kalita K, et al. Bioactive guided fractions of Annona reticulata L. bark: protection against liver toxicity and inflammation through inhibiting oxidative stress and proinflammatory cytokines. Front Pharmacol 2016; 7:168.

Lee TY, Mai LM, Wang GJ, Chiu JH, Lin YL, Lin HC. Protective mechanism of salvia miltiorrhiza on carbon tetrachloride-induced acute hepatotoxicity in rats. J Pharmacol Sci 2003; 91:202-10.

Banna H, SolimanM., Wabel N. Hepatoprotective effects of Thymus and Salvia essential oils on paracetamol-induced toxicity in rats. J Essent Oil Res 2013; 3:41-7.

Xavier CP, Pereira-Wilson C. Medicinal plants of the genuses Salvia and Hypericum are sources of anticolon cancer compounds: Effects on PI3K/Akt and MAP kinases pathways. Pharma Nutrition 2016; 4:112-22.

Zhou R, He LF, Li YJ, Shen Y, Chao RB, Du JR. Cardioprotective effect of water and ethanol extract of Salvia miltiorrhiza in an experimental model of myocardial infarction. J Ethnopharmacol 2012; 139:440-6.

Porres-Martínez M, González-Burgos E, Carretero ME, Gómez-Serranillos MP. Protective properties of Salvia lavandulifolia Vahl. essential oil against oxidative stress-induced neuronal injury. Food Chem Toxicol 2015; 80:154-62.

Choi JK, Oh HM, Park JH, Choi JH, Sa KH, Kang YM, et al. Salvia plebeia extract inhibits the inflammatory response in human rheumatoid synovial fibroblasts and a murine model of arthritis. Phytomedicine 2015; 22:415-22.

Baser KHC, Beis SH, í–zek T. Composition of the essential oil of Salvia cryptantha Montbret et Aucher ex Benth. from Turkey. J Essent Oil Res 1995; 7:113-4.

Ulubelen A, Topcu G, Terem B. Abietna diterpenoids from the roots of Salvia cryptantha. Phytochem 1987; 26:1534-5.

Bold RJ, Termuhlen PM, McConkey DJ. Apoptosis, cancer and cancer therapy. Surg Oncol 1997; 6:133-42.

Shi J, Aisaki K, Ikawa Y, Wake K. Evidence of hepatocyte apoptosis in rat liver after the administration of carbon tetrachloride. Am J Pathol 1998; 153:515-25.

Yasuda M, Okabe T, Itoh J, Takekoshi S, Hasegawa H Nagata, H, et al. Differentiation of necrotic cell death with or without lysosomal activation: application of acute liver injury models induced by carbon tetrachloride (CCl4) and dimethylnitrosamine (DMN). J Histochem Cytochem 2000; 48:1331-9.

Jin Q, Jiang S, Wu YL, Bai T, Yang Y, Jin X, et al. Hepatoprotective effect of cryptotanshinone from Salvia miltiorrhiza in D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure. Phytomedicine 2014; 21:141-7.

Author biographies is not available.