Anti-apoptotic and anti-inflammatory activity of Gentiana lutea root extract

Advances in Traditional Medicine - Tập 20 Số 4 - Trang 619-630 - 2020
Teresa Cafaro1, Veronica Carnicelli1, Giovanni Caprioli2, Filippo Maggi2, Giuseppe Celenza1, Mariagrazia Perilli1, Argante Bozzi3, Gianfranco Amicosante1, Fabrizia Brisdelli1
1Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio – Coppito 2, 67100 L'Aquila, Italy
2School of Pharmacy, University of Camerino, Camerino, Italy
3National Institute of Biostructures and Biosystems (NIBB), Rome, Italy

Tóm tắt

AbstractGentiana lutea roots have been widely used in the traditional medicine, especially for their stomachic properties. In this study, the effect of G. lutea root methanol extract on SH-SY5Y cell survival and on anti-proliferative activity of pro-apoptotic agents was evaluated. In neuroblastoma cell line SH-SY5Y, the extract did not exhibit any cytotoxic activity, but protected cells from vinblastine-induced apoptosis. In the combined treatment with 200 µg/ml extract plus 0.1 µM vinblastine, extract significantly increased cell survival, reduced the percentage of apoptotic cells and decreased caspase-3 activity if compared with the vinblastine alone treatment. The anti-apoptotic activity of the extract was associated to the down-regulation of Sirt-1 protein and to the increase of anti-apoptotic Bcl-2 protein expression and intracellular GSH levels. Since the apoptosis modulation was evidenced on a neuroblastoma cell line, G. lutea extract could have a promising potential as a neuroprotective agent. Moreover, G. lutea root extract exhibited anti-inflammatory activity, since it inhibited LPS-induced expression of TNF-α in macrophage RAW264.7 cells.

Từ khóa


Tài liệu tham khảo

Aberham A, Schwaiger S, Stuppner H, Ganzera M (2007) Quantitative analysis of iridoids, secoiridoids, xanthones and xanthone glycosides in Gentiana lutea L. roots by RP-HPLC and LC-MS. J Pharm Biomed Anal 45:437–442

Akileshwari C, Muthenna P, Nastasijević B, Joksić G, Petrash JM, Reddy GB (2012) Inhibition of aldose reductase by Gentiana lutea extracts. Exp Diabetes Res 2012:147965

Amin A (2008) Ketaconazole-induced testicular damage in rats reduced by Gentiana extract. Exp Toxicol Pathol 59:377–384

Banach M, Juranek JK, Zygulska AL (2016) Chemotherapy-induced neuropathies—a growing problem for patients and health care providers. Brain Behav 7:e00558

Chang H-C, Guarente L (2014) SIRT1 and other sirtuins in Metabolism. Trends Endocrinol Metab 25:138–145

Fang J, Nakamura H, Iyer AK (2007) Tumor-targeted induction of oxystress for cancer therapy. J Drug Target 15:475–486

Gao L, Xiang L, Luo Y, Wang G, Li J, Qi J (2010) Gentisides C-K: nine new neuritogenic compounds from the traditional Chinese medicine Gentiana rigescens Franch. Bioorg Med Chem 18:6995–7000

Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140:918–934

Haraguchi H, Tanaka Y, Kabbash A, Fujioka T, Ishizu T, Yagi A (2004) Monoamine oxidase inhibitors from Gentiana lutea. Phytochemistry 65:2255–2260

He YM, Zhu S, Ge YW, Cai SQ, Komatsu K (2015) The anti-inflammatory secoiridoid glycosides from Gentianae Scabrae radix: the root and rhizome of Gentiana scabra. J Nat Med 69:303–312

Hernandez-Jimenez M, Hurtado O, Cuartero MI, Ballesteros I, Moraga A, Pradillo JM, McBurney MW, Lizasoain I, Moro MA (2013) Silent information regulator 1 protects the brain against cerebral ischemic damage. Stroke 44:2333–2337

Hisahara S, Chiba S, Matsumoto H, Horio Y (2005) Transcriptional regulation of neuronal genes and its effect on neural functions: NAD-dependent histone deacetylase SIRT1 (Sir2alpha). J Pharmacol Sci 98:200–204

Jia N, Chu W, Li Y, Ding L, Duan J, Cui J, Cao S, Zhao C, Wu Y, Wen A (2016) Iridoid glycosides from the flowers of Gentiana macrophylla Pall. ameliorate collagen-induced arthritis in rats. J Ethnopharmacol 189:1–9

Kesavan R, Potunuru UR, Nastasijević B, Avaneesh T, Joksić G, Dixit M (2013) Inhibition of vascular smooth muscle cell proliferation by Gentiana lutea root extracts. PLoS ONE 18:e61393

Köhlex C, Orrenius S, Zhivatovsky B (2002) Evaluation of caspase activity in apoptotic cells. J Immunol Methods 265:97–110

Kumaran A, Karunakaran R (2007) In vitro antioxidant activities of methanol extracts of five Phyllantus species from India. Food Sci Technol 40:344–352

LeBel CP, Ishiropoulos H, Bondy SC (1992) Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive species formation and oxidative stress. Chem Res Toxicol 5:227–231

Majithia N, Loprinzi CL, Smith TJ (2016) New practical approaches to chemotherapy-induced neuropathic pain: prevention, assessment and treatment. Oncology (Williston Park) 30:1–13

Menkovic N, Juranic Z, Stanojkovic T, Raonic-Stevanovic T, Savikin K, Zdunić G, Borojevic N (2010) Radioprotective activity of Gentiana lutea extract and mangiferin. Phytother Res 24:1693–1696

Mortenson MM, Galante JG, Gilad O, Schlieman MG, Virudachalam S, Kung HJ, Bold RJ (2007) BCL-2 functions as an activator of the AKT signaling pathway in pancreatic cancer. J Cell Biochem 102:1171–1179

Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

Mustafa AM, Caprioli G, Dikmen M, Kaya E, Maggi F, Sagratini G, Vittori S, Öztürk Y (2015a) Evaluation of neuritogenic activity of cultivated, wild and commercial roots of Gentiana lutea L. J Funct Foods 19:164–173

Mustafa AM, Caprioli G, Ricciutelli M, Maggi F, Marin R, Vittori S, Sagratini G (2015b) Comparative HPLC/ESI-MS and HPLC/DAD study of different populations of cultivated, wild and commercial Gentiana lutea L. Food Chem 174:426–433

Nastasijević B, Lazarević-Pašti T, Dimitrijević-Branković S, Pašti I, Vujačić A, Joksić G, Vasić V (2012) Inhibition of myeloperoxidase and antioxidative activity of Gentiana lutea extracts. J Pharm Biomed Anal 66:191–196

Niu Y-T, Zhao Y-P, Jiao Y-F, Zheng J, Yang W-L, Zhou R, Niu Y, Sun T, Li Y-X, Yu J-Q (2016) Protective effect of gentiopicroside against dextran sodium sulfate induced colitis in mice. Int Immunopharmacol 39:16–22

Ordoñez AAL, Gomez JD, Vattuone MA, Isla MI (2006) Antioxidant activities of Sechium edule (Jacq.) Swartz extracts. Food Chem 97:452–458

Ouyang Y-B, Giffard RG (2004) Cellular neuroprotective mechanisms in cerebral ischemia: Bcl-2 family proteins and protection of mitochondrial function. Cell Calcium 36:303–311

Ouyang Y-B, Giffard RG (2014) MicroRNAs affect BCL-2 family proteins in the setting of cerebral ischemia. Neurochem Int 77:2–8

Pan J, Zhao J-L, Zhang J, Li W-J, Wang J-Z (2016) Phytochemistry and pharmacological activities of the Genus Gentiana (Gentianaceae). Chem Biodivers 13:107–150

Rahman I, Kode A, Biswas SK (2006) Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat Protoc 1:3159–3165

Rojas A, Bah M, Rojas JI, Gutierrez DM (2000) Smooth muscle relaxing activity of gentiopicroside isolated from Gentiana spathacea. Planta Med 66:765–767

Schmieder A, Schwaiger S, Csordas A, Backovic A, Messner B, Wick G, Stuppner H, Bernhard D (2007) Isogentisin—a novel compound for the prevention of smoking-caused endothelial injury. Atherosclerosis 194:317–325

Schröder S, Beckmann K, Franconi G, Meyer-Hamme G, Friedemann T, Greten HJ, Rostock M, Efferth T (2013) Can medical herbs stimulate regeneration or neuroprotection and treat neuropathic pain in chemotherapy-induced peripheral neuropathy? Evidence Based Complement Altern Med 2013:423713

Steiner N, Balez R, Karunaweera N, Lind JM, Münch G, Ooi L (2016) Neuroprotection of Neuro2a cells and the cytokine suppressive and anti-inflammatory mode of action of resveratrol in activated RAW264.7 macrophages and C8-B4 microglia. Neurochem Int 95:46–54

Stratil P, Klejdus B, Kubáň V (2006) Determination of total content of phenolic compounds and their antioxidant activity in vegetables—evaluation of spectrophotometric methods. J Agric Food Chem 54:607–616

Terrano DT, Upreti M, Chambers TC (2010) Cyclic-dependent kinase 1-mediated Bcl-XL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol 30:640–656

Traverso N, Ricciarelli R, Nitti M, Marengo B, Furfaro AL, Pronzato MA, Marinari M, Domenicotti C (2013) Role of glutathione in cancer progression and chemoresistance. Oxidative Med Cell Longev 2013:972913

Tucker CA, Kapanen AI, Chikh G, Hoffman BG, Kyle AH, Wilson IM, Masin D, Gascoyne RD, Bally M, Klasa RJ (2008) Silencing Bcl-2 in models of mantle cell lymphoma is associated with decreases in cyclin D1, nuclear factor-kappaB, p53, bax, and p27 levels. Mol Cancer Ther 7:749–758

Wang YM, Xu M, Wang D, Yang CR, Zeng Y, Zhang YJ (2013) Anti-inflammatory compounds of “Qin-Jiao”, the roots of Gentiana dahurica (Gentianaceae). J Ethnopharmacol 147:341–348

Wang C-Y, Sun Z-N, Wang M-X, Zhang C (2018) SIRT1 mediates salidroside-elicited protective effects against MPP+-induced apoptosis and oxidative stress in SH-SY5Y cells: involvement in suppressing MAPK pathways. Cell Biol Int 42:84–94

Yamada H, Kikuchi S, Inui T, Takahashi H, Kimura K (2014) Gentiolactone, a secoiridoid dilactone from Gentiana triflora, inhibits TNF-α, iNOS and Cox-2 mRNA expression and blocks NF-κB promoter activity in murine macrophages. PLoS ONE 9:e113834

Youle RJ, Strasser A (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9:47–59

Zhao Y, Luo P, Guo Q, Li S, Zhang L, Zhao M, Xu H, Yang Y, Poon W, Fei Z (2012) Interactions between SIRT1 and MAPK/ERK regulate neuronal apoptosis induced by traumatic brain injury in vitro and in vivo. Exp Neurol 237:489–498

Zhao ZY, Gao YY, Gao L, Zhang M, Wang H, Zhang CH (2017) Protective effects of bellidifolin in hypoxia-induced in pheochromocytoma cells (PC12) and underlying mechanisms. J Toxicol Environ Health A 80:1187–1192

Zou X-D, Guo S-Q, Hu Z-W, Li W-L (2016) NAMPT protects against 6-hydroxydopamine-induced neurotoxicity in PC12 cells through modulating SIRT1 activity. Mol Med Rep 13:4058–4064