Evaluation of Toxic Effects of Dictamnus albus L. Extracts on PC-12 and SHSY-5Y Cell Lines and Investigation of Antioxidant Activity
Öz
This study investigated the antioxidant and cytotoxic properties of the Dictamnus albus L. plant grown in Türkiye. The aerial parts and roots of the plant were evaluated qualitatively in terms of chemical content. Total phenol and flavonoid amounts were calculated by spectrophotometric methods, antioxidant activity was tested with DPPH and ABTS radical scavenging activity assay. In addition, cell viability determination in PC-12 and SHSY-5Y cell lines was evaluated by performing MTT (3-4,5-dimethyl-thiazolyl-2,5-diphenyltetrazolium bromide) test. According to the results, both parts of the plant gave negative results in the tannin, cyanogenetic glycoside, anthraquinone, cardiac glycoside, and anthocyanoside identification tests, while they gave positive results in the alkaloid, coumarin, saponin, carbohydrate identification tests. While the total amount of phenol was calculated as 77.13 ± 5.73 mgGAE gexracts-1 in the extract prepared with methanol from the aerial parts of the plant (D.A Herba), it was calculated as 43.81 ± 9.49 mgGAE gexracts-1 in the extract prepared from the roots (D.A Root). The total flavonoid content could only be calculated in the D.A Herba extract (19.11 ± 0.16 mgCA gextract-1). Although the DPPH radical scavenging effect of the extracts was higher in D.A Herba extract, the ABTS radical scavenging effects were found similar in both D.A Herba and D.A Root extracts. According to the toxicity test, D.A Root extract reduced the viability below 50% (43.17 ± 3.44%) at 500 µg mL-1, but D.A Herba extract was found to be more toxic at the same concentration with 19.53 ± 0.183% in the PC-12 cell line. However, D.A. Herba and D.A.Root extract increased cell proliferation in the SHSY-5Y cell line at 3.25 µg/mL concentrations with 122.87±6.29 and 112.78±7.00%, respectively. The results suggest that D. albus may be a promising candidate for the new phytopharmaceuticals due to its neuroprotective effects.
Anahtar Kelimeler
Kaynakça
- Alam MN, Bristi NJ, Rafiquzzaman M 2013. Review on In Vivo and In Vitro Methods Evaluation of Antioxidant Activity. Saudi Pharm J 21(2): 143-152.
- Baytop T 1999. Türkiye’de Bitkilerle Tedavi, Nobel Tıp Kitapevleri Yayını, 2. Baskı, İstanbul, 480 sy.
- Borjan D, Leitgeb M, Knez Ž, Hrnčič M K 2020. Microbiological and Antioxidant Activity of Phenolic Compounds in Olive Leaf Extract. Molecules 25(24): 5946.
- Cao D, Hao Q, Sun R, Wang Y, Zhang Y, Zhou H 2022. Multiple stoichiometric methods combined with FT-IR spectroscopy for screening new medicinal parts from Dictamnus dasycarpus Turcz with pronounced antioxidant potential. J. Mol. Struct,1252: 132187.
- Chang J, Xuan LJ, Xu YM, Zhang JS 2002. Cytotoxic Terpenoid and Immunosuppressive Phenolic Glycosides from the Root Bark of Dictamnus dasycarpus. Planta Med 68(5):425-9
- Choi HG, Lee DS, Li B, Jun KY, Jeon, GS, Kim YC 2011. Neuroprotective effect of the water-insoluble fraction of root barks of Dictamnus dasycarpus 70% ethanolic extract on glutamate-induced oxidative damage in mouse hippocampal HT22 cells. Korean J. Pharmacogn.42(2):175-181.
- Compton J, Akeroyd J 2019. The Correct Name for The Whıte-Flowered Varıant of Dictamnus albus L. (Rutaceae). Contribuţii Botanice 79-89
- Gao P, Wang L, Zhao L, Lu YY, Zeng KW, Zhao MB, Jiang Y, Tu PF, Guo XY 2021. Rapid Identification, Isolation, and Evaluation on Anti-Neuroinflammatory Activity of Limonoids Derivatives from The Root Bark of Dictamnus dasycarpus. J Pharm Biomed Anal 5; 200:114079
- Gnatiuk АМ 2019. Features of Dictamnus albus (Rutaceae) in the pregenerative period of ontogeny in MM Gryshko National Botanical Garden in Ukraine. Regul. mech. Biosyst 10(4):470-476.
- Gyamfi MA, Yonamine M, Aniya Y 1999. Free-Radical Scavenging Action of Medicinal Herbs from Ghana:Thonningia sanguinea on Experimentally-Induced Liver Injuries. Gen. Pharmacol 32:661-667
- Jeong GS, Byun E, Li B, Lee DS, Kim YC, An RB 2010. Neuroprotective Effects of Constituents of The Root Bark of Dictamnus dasycarpus in Mouse Hippocampal Cells. Arch Pharm Res 33(8):1269-75
- Kähkönen MP, Hopia AI, Vuorela HJ, Rauha JP, Pihlaja K, Kujala TS, Heinonen M 1999. Antioxidant Activity of Plant Extracts Containing Phenolic Compounds. Agric. Food Chem 47(10):3954–3962.
- Karatoprak G.S, Ilgün S, Koşar M 2017. Phenolic Composition, Anti-Inflammatory, Antioxidant, and Antimicrobial Activities of Alchemilla mollis (Buser) Rothm. Chem. Biodivers 14(9): e170015
- Lv M, Xu P, Tian Y, Liang J, Gao Y, Xu F, Zhang Z, Sun J 2015. Medicinal Uses, Phytochemistry and Pharmacology Of The Genus Dictamnus (Rutaceae). J Ethnopharmacol 2(171):247-63
- Nissar S, Raja WY, Majid N, Nawchoo IA, Bhat ZA 2021. Pharmacognostic Characterization and Development of Quality Control Standards for Dictamnus albus: A Comparative Study of Different Parts. Adv. Trad. Med 1-14
- Pavlović DR, Zlatković B, Živanović S, Kitić D, Golubović T 2018. Serbian Rutaceae Species: Comparison of Flavonoid Contents, Coumarin Compounds and Radical Scavenging Activity. Bıol Nyssana 9(1):37-43
- Plantlist 2022. Dictamnus albus L. http://www.theplantlist.org/tpl1.1/search?q=dictamnus+albus. (Alınma tarihi:25.03.2022)
- Re R, Pellegrını N, Proteggente A, Pannala A, Yang M, Rıce-Evans C 1999. Antioxidant Activity Applying an Improved ABTS Radical Cation Decolorization Assay. Free Radic. Biol. Med 26(9-10): 1231-1237.
- Rohim P, Arung ET, Kusuma IW 2018. Potential of Antioxidant and Toxicity of Some Medical Plants Used by Sub-Ethnic Communities of Bahau in East Kalimanta. IOP Conf. Ser.: Earth Environ. Sc 144:012026
- Sakar MK, Tanker M 1991. Fitokimyasal Analizler. Ankara Üniversitesi Eczacılık Fakültesi Yayınları, Ankara, 67.
- Sharma NS, Karan A, Lee D, Yan Z, Xie J 2021. Advances in Modeling Alzheimer's Disease In Vitro. Advanced NanoBiomed Research. 1(12): 2100097.
- Siddiqui MA, Farshori NN, Al-Oqail MM, Pant AB, Al-Khedhairy AA 2021. Neuroprotective Effects of Withania somnifera on 4-Hydroxynonenal Induced Cell Death in Human Neuroblastoma SH-SY5Y Cells Through ROS Inhibition and Apoptotic Mitochondrial Pathway. Neurochem. Res, 46(2): 171-182
- Singleton Vl, Orthofer R, Lamuela-Raventós Rm 1999. Analysis of Total Phenols and Other Oxidation Substrates and Antioxidants by Means of Folin-Ciocalteu Reagent. Meth. Enzymol 299:152-178.
- Sun JB, Jiang N, Lv MY, Wang P, Xu FG, Liang JY, Qu W 2015. Limonoids from the Root Bark of Dictamnus angustifolius: Potent Neuroprotective Agents with Biometal Chelation and Halting Copper Redox Cycling Properties. RSC Adv 5: 24750-2475
- Wang H, Shao B, Yu H, Xu F, Wang P, Yu K, Han Y, Song M, Li Y, Cao Z 2019. Neuroprotective Role of Hyperforin on Aluminum Maltolate-Induced Oxidative Damage and Apoptosis in PC12 Cells and SH-SY5Y Cells. Chem Biol Interact 1(299):15-26
- Yoon JS, Sung SH, Kim YC 2008. Neuroprotective Limonoids of Root Bark of Dictamnus dasycarpus. J Nat Prod 71(2):208-11
- Yucel C, Seker Karatoprak G 2017. Development and Evaluation of the Antioxidant Activity of Liposomes and Nanospheres Containing Rosmarinic Acid. Farmacia 65(1): 40-45
- Zhang M, Wang Y, Wong RM, Yun KKL, Li R. 2022. Fine particulate matter induces endoplasmic reticulum stress-mediated apoptosis in human SH-SY5Y cells. Neurotoxicology. 88: 187-195.
- Zhıshen J, Mengcheng T, Jıanmıng W 1999. The Determination of Flavonoid Contents in Mulberry and Their Scavenging Effects on Superoxide Radicals. Food Chem 64(4): 555-559.
Dictamnus albus L’ a Ait. Ekstrelerin PC-12 ve SHSY-5Y Hücre Hatlarında Toksik Etkilerinin Değerlendirilmesi ve Antioksidan Aktivitesinin Araştırılması
Öz
Bu çalışmada, Türkiye’de yetişen Dictamnus albus L. bitkisinin, antioksidan ve sitotoksik özellikleri araştırılmıştır. Bitkinin topraküstü ve kök kısımları kimyasal içerik bakımından kalitatif olarak değerlendirilmiştir. Toplam fenol ve flavonoit miktarı spektrofotometrik yöntemlerle hesaplanmış, antioksidan aktivitesi DPPH ve ABTS radikalini süpürücü aktivite deneyi ile test edilmiştir. Ayrıca PC-12 ve SHSY-5Y hücre hatlarında canlılık tayini MTT (3-4,5-dimetil-tiyazolil-2,5-difeniltetrazolyum bromür) testi yapılarak değerlendirilmiştir. Sonuçlara göre; bitkinin her iki kısmı da tanen, siyanogenetik glikozit, antrakinon, kardiyak glikozit ve antosiyanozit teşhis deneylerinde negatif sonuç verirken, alkaloit, kumarin, saponin, karbonhidrat teşhis deneylerinde pozitif sonuç vermiştir. Bitkinin topraküstü kısımlarından metanol ile hazırlanan ekstresinde (D.A Herba) toplam fenol miktarı 77,13 ± 5,73 mgGAE gekstre-1 olarak hesaplanırken, köklerinden hazırlanan ekstresinde (D. A Root) ise 43,81 ± 9,49 mgGAE gekstre-1 olarak hesaplanmıştır. Toplam flavonoit içeriği ise yalnızca D.A Herba ekstresinde hesaplanabilmiştir (19,11 ± 0,16 mgCA gekstre-1 ). Ekstrelerin DPPH radikalini süpürücü etksi D.A Herba ekstresinde daha yüksek bulunurken, ABTS radikalini süpürücü etkileri her iki ekstrede de benzer bulunmuştur. Toksisite deneyi sonuçlarına göre, PC-12 hücre hattında 500 µg mL-1’de D.A Root ekstresi canlılığı % 50’nin altına düşürmüş (% 43,17 ± 3,44), ancak D.A Herba ekstresi aynı konsantrasyonda %. 19,53 ± 0,183 ile daha toksik etkili bulunmuştur. Ancak, D.A. Herba ve D.A.Root ekstresi SHSY-5Y hücre hattında 3,25 µg mL-1 konsantrasyonlarda sırasıyla % 122,87 ± 6,29 ve 112,78 ± 7,00 canlılık oranı ile hücre proliferasyonu arttırmıştır. Sonuçlar D. albus bitkisinin nöroprotektif etkileri sebebiyle yeni fitofarmasötiklerin için potansiyel adaylar olabileceğini düşündürmektedir.
Anahtar Kelimeler
Kaynakça
- Alam MN, Bristi NJ, Rafiquzzaman M 2013. Review on In Vivo and In Vitro Methods Evaluation of Antioxidant Activity. Saudi Pharm J 21(2): 143-152.
- Baytop T 1999. Türkiye’de Bitkilerle Tedavi, Nobel Tıp Kitapevleri Yayını, 2. Baskı, İstanbul, 480 sy.
- Borjan D, Leitgeb M, Knez Ž, Hrnčič M K 2020. Microbiological and Antioxidant Activity of Phenolic Compounds in Olive Leaf Extract. Molecules 25(24): 5946.
- Cao D, Hao Q, Sun R, Wang Y, Zhang Y, Zhou H 2022. Multiple stoichiometric methods combined with FT-IR spectroscopy for screening new medicinal parts from Dictamnus dasycarpus Turcz with pronounced antioxidant potential. J. Mol. Struct,1252: 132187.
- Chang J, Xuan LJ, Xu YM, Zhang JS 2002. Cytotoxic Terpenoid and Immunosuppressive Phenolic Glycosides from the Root Bark of Dictamnus dasycarpus. Planta Med 68(5):425-9
- Choi HG, Lee DS, Li B, Jun KY, Jeon, GS, Kim YC 2011. Neuroprotective effect of the water-insoluble fraction of root barks of Dictamnus dasycarpus 70% ethanolic extract on glutamate-induced oxidative damage in mouse hippocampal HT22 cells. Korean J. Pharmacogn.42(2):175-181.
- Compton J, Akeroyd J 2019. The Correct Name for The Whıte-Flowered Varıant of Dictamnus albus L. (Rutaceae). Contribuţii Botanice 79-89
- Gao P, Wang L, Zhao L, Lu YY, Zeng KW, Zhao MB, Jiang Y, Tu PF, Guo XY 2021. Rapid Identification, Isolation, and Evaluation on Anti-Neuroinflammatory Activity of Limonoids Derivatives from The Root Bark of Dictamnus dasycarpus. J Pharm Biomed Anal 5; 200:114079
- Gnatiuk АМ 2019. Features of Dictamnus albus (Rutaceae) in the pregenerative period of ontogeny in MM Gryshko National Botanical Garden in Ukraine. Regul. mech. Biosyst 10(4):470-476.
- Gyamfi MA, Yonamine M, Aniya Y 1999. Free-Radical Scavenging Action of Medicinal Herbs from Ghana:Thonningia sanguinea on Experimentally-Induced Liver Injuries. Gen. Pharmacol 32:661-667
- Jeong GS, Byun E, Li B, Lee DS, Kim YC, An RB 2010. Neuroprotective Effects of Constituents of The Root Bark of Dictamnus dasycarpus in Mouse Hippocampal Cells. Arch Pharm Res 33(8):1269-75
- Kähkönen MP, Hopia AI, Vuorela HJ, Rauha JP, Pihlaja K, Kujala TS, Heinonen M 1999. Antioxidant Activity of Plant Extracts Containing Phenolic Compounds. Agric. Food Chem 47(10):3954–3962.
- Karatoprak G.S, Ilgün S, Koşar M 2017. Phenolic Composition, Anti-Inflammatory, Antioxidant, and Antimicrobial Activities of Alchemilla mollis (Buser) Rothm. Chem. Biodivers 14(9): e170015
- Lv M, Xu P, Tian Y, Liang J, Gao Y, Xu F, Zhang Z, Sun J 2015. Medicinal Uses, Phytochemistry and Pharmacology Of The Genus Dictamnus (Rutaceae). J Ethnopharmacol 2(171):247-63
- Nissar S, Raja WY, Majid N, Nawchoo IA, Bhat ZA 2021. Pharmacognostic Characterization and Development of Quality Control Standards for Dictamnus albus: A Comparative Study of Different Parts. Adv. Trad. Med 1-14
- Pavlović DR, Zlatković B, Živanović S, Kitić D, Golubović T 2018. Serbian Rutaceae Species: Comparison of Flavonoid Contents, Coumarin Compounds and Radical Scavenging Activity. Bıol Nyssana 9(1):37-43
- Plantlist 2022. Dictamnus albus L. http://www.theplantlist.org/tpl1.1/search?q=dictamnus+albus. (Alınma tarihi:25.03.2022)
- Re R, Pellegrını N, Proteggente A, Pannala A, Yang M, Rıce-Evans C 1999. Antioxidant Activity Applying an Improved ABTS Radical Cation Decolorization Assay. Free Radic. Biol. Med 26(9-10): 1231-1237.
- Rohim P, Arung ET, Kusuma IW 2018. Potential of Antioxidant and Toxicity of Some Medical Plants Used by Sub-Ethnic Communities of Bahau in East Kalimanta. IOP Conf. Ser.: Earth Environ. Sc 144:012026
- Sakar MK, Tanker M 1991. Fitokimyasal Analizler. Ankara Üniversitesi Eczacılık Fakültesi Yayınları, Ankara, 67.
- Sharma NS, Karan A, Lee D, Yan Z, Xie J 2021. Advances in Modeling Alzheimer's Disease In Vitro. Advanced NanoBiomed Research. 1(12): 2100097.
- Siddiqui MA, Farshori NN, Al-Oqail MM, Pant AB, Al-Khedhairy AA 2021. Neuroprotective Effects of Withania somnifera on 4-Hydroxynonenal Induced Cell Death in Human Neuroblastoma SH-SY5Y Cells Through ROS Inhibition and Apoptotic Mitochondrial Pathway. Neurochem. Res, 46(2): 171-182
- Singleton Vl, Orthofer R, Lamuela-Raventós Rm 1999. Analysis of Total Phenols and Other Oxidation Substrates and Antioxidants by Means of Folin-Ciocalteu Reagent. Meth. Enzymol 299:152-178.
- Sun JB, Jiang N, Lv MY, Wang P, Xu FG, Liang JY, Qu W 2015. Limonoids from the Root Bark of Dictamnus angustifolius: Potent Neuroprotective Agents with Biometal Chelation and Halting Copper Redox Cycling Properties. RSC Adv 5: 24750-2475
- Wang H, Shao B, Yu H, Xu F, Wang P, Yu K, Han Y, Song M, Li Y, Cao Z 2019. Neuroprotective Role of Hyperforin on Aluminum Maltolate-Induced Oxidative Damage and Apoptosis in PC12 Cells and SH-SY5Y Cells. Chem Biol Interact 1(299):15-26
- Yoon JS, Sung SH, Kim YC 2008. Neuroprotective Limonoids of Root Bark of Dictamnus dasycarpus. J Nat Prod 71(2):208-11
- Yucel C, Seker Karatoprak G 2017. Development and Evaluation of the Antioxidant Activity of Liposomes and Nanospheres Containing Rosmarinic Acid. Farmacia 65(1): 40-45
- Zhang M, Wang Y, Wong RM, Yun KKL, Li R. 2022. Fine particulate matter induces endoplasmic reticulum stress-mediated apoptosis in human SH-SY5Y cells. Neurotoxicology. 88: 187-195.
- Zhıshen J, Mengcheng T, Jıanmıng W 1999. The Determination of Flavonoid Contents in Mulberry and Their Scavenging Effects on Superoxide Radicals. Food Chem 64(4): 555-559.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Yapısal Biyoloji |
| Bölüm | ARAŞTIRMA MAKALESİ (Research Article) |
| Yazarlar | |
| Yayımlanma Tarihi | 30 Aralık 2022 |
| Gönderilme Tarihi | 25 Ocak 2022 |
| Kabul Tarihi | 30 Mayıs 2022 |
| Yayımlandığı Sayı | Yıl 2022 |
Kaynak Göster
2022-JIF = 0.500
2022-JCI = 0.170
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