Investigation of the Phytochemical Components and Antiepileptic Potential of Helichrysum pallasii (Sprengel) Ledeb. Through in vitro and in vivo Studies

Oruç Yunusoğlu; Muzaffer Mukemre; Rabia Sena Dalkılıç

doi:10.18016/ksutarimdoga.vi.1676615

TR EN

Helichrysum pallasii (Sprengel) Ledeb. Türünün Fitokimyasal Bileşenleri ile Antiepileptik Potansiyelinin in vitro ve in vivo Olarak Araştırılması

Öz

Bu çalışmada Doğu Anadolu’da epilepsi tedavisinde halk ilacı olarak kullanılan Helichrysum pallasii (Sprengel) Ledeb. türünün in vitro ve in vivo antiepileptik aktiviteleri ve içerdiği biyoaktif bileşenleri incelenmiştir. Bu bitkinin antiepileptik özellikleri in vitro antioksidan (etanol ve infuzyon sırasıyla=FCR: 112.0 ve 60.0 mg GAE/gE; FRAP: 2687.5 ve 1502.9 µmol Fe 2+ /gE; ORAC: 3200.7 ve 2095.1 µmol Trolox Eq./gE; DPPH: IC50=440.5 ve 661.0 µg ml-1; metal şelatlama: IC50= 185.8 ve 443.9 µg ml-1)) ve epilepsi ilintili Butirilkolinesteraz (IC50=374.5 ve 817.9 µg ml-1), Asetilkolinesteraz (IC50=242 ve 682.0 µg ml-1) enzimleri ve GABA-T (IC50=350.3 ve 676.4 µg ml-1) aktivitesi deneyleri ve in vivo araştırmalarla detaylı bir şekilde araştırılmıştır. In vivo çalışmalar farelerde pentilentetrazol ile oluşturulan kindling epilepsi modelinde bitkinin etanol ekstresi ve infüzyonunun karşılaştırmalı olarak 3 farklı dozda (60, 120, ve 180 mg kg-1) antiepileptik etki açısından incelenmesi çalışmalarından oluşmaktadır. Her iki ekstrenin özellikle 120 ve 180 mg kg-1 dozlarda nöbet skorlarının azalttığı görüldü (p<0,05). Ayrıca biyokimyasal olarak, PTZ grubunda malondialdehit (MDA) düzeyinin arttığı ve doza bağımlı olarak bitki ekstreleri uygulanan gruplarda MDA düzeyinin önemli derecede azaldığı belirlendi (p<0,05). Ayrıca, bitki ekstreleri uygulanan gruplarda (özellikle etanol ekstresi) antioksidan parametrelerin (CAT, SOD ve GSH Px) ve NO düzeylerinin istatiksel olarak arttığı tespit edildi. Fitokimyasal çalışmalar bitki ekstrelerinin yüksek miktarda fenolik bileşik (kafeoilkinik asit ve kuersetin türevleri), çeşitli uçucu bileşenler ve yağ asitlerini içerdiklerini göstermiştir. Bulgularımız, yüksek miktarda biyoaktif bileşen içeren etanol ekstresinin kayda değer bir şekilde hem in vitro hem de in vivo antiepileptik aktiviteye sahip olduğunu göstermiş ve H. pallasii türünün geleneksel halk hekimliği kullanımı ile benzer yöndedir. İleride konu ile ilgili daha ayrıntılı mekanistik çalışmaların yapılması önerilmektedir.

Anahtar Kelimeler

Investigation of the Phytochemical Components and Antiepileptic Potential of Helichrysum pallasii (Sprengel) Ledeb. Through in vitro and in vivo Studies

Abstract

This study investigated the bioactive components and in vitro and in vivo antiepileptic properties of the Helichrysum pallasii (Sprengel) Ledeb. species, which has long been used in traditional medicine in Eastern Anatolia. Pronounced antiepileptic properties of this plant were detected through in vitro antioxidant (ethanol and infusion=FCR: 112.0 and 60.0 mg GAE/gE; FRAP: 2687.5 and 1502.9 µmol Fe 2+ /gE; ORAC: 3200.7 and 2095.1 µmol Trolox Eq./gE; DPPH: IC50=440.5 and 661.0 µg ml-1; metal chelatin: IC50= 185.8 and 443.9 µg ml-1 respectively) and epilepsy-related enzyme Butyrylcholinesterase (IC50=374.5 and 817.9 µg ml-1 respectively), Acetylcholinesterase (IC50=242 and 682.0 µg ml-1 respectively) enzymes and GABA-T (IC50=350.3 and 676.4 µg ml-1 respectively) activity inhibition experiments and detailed in vivo investigations. In vivo, investigations included comparisons of the antiepileptic effects of three different dosages (60, 120, and 180 mg kg-1) of extract and infusion in a pentylenetetrazol kindling epilepsy model. It was found that the seizure scores were significantly reduced by both extracts, particularly at doses of 120 and 180 mg kg-1 (p<0.05). Biochemically, it was determined that malondialdehyde (MDA) levels increased in the PTZ group, whereas MDA levels significantly decreased in the plant extract-treated groups in a dose-dependent manner (p<0.05). Furthermore, it was shown that the groups administered plant extract (ethanol extract specifically) had statistically higher levels of nitric oxide and antioxidant parameters (CAT, SOD, and GSH-Px). Phytochemical studies demonstrated that plant extracts contained a high amount of phenolic compounds (caffeoylquinic acid and quercetin derivatives) and various volatile and fatty acid compounds. Our findings revealed that the ethanol extract, which was rich in bioactive compounds, exhibited strong antiepileptic effects both in vivo and in vitro, which is in line with the use of the H. pallasii species in traditional medicine. It is recommended that more detailed mechanistic studies be conducted on this subject in the future.

Keywords

Supporting Institution

Van Yuzuncu Yil University Scientific Research Projects Council for providing financial assistance of the research

Project Number

TSA-2017-6079

Ethical Statement

None of the authors has a commercial interest, financial interest, and/or other relationship with manufacturers of pharmaceuticals, laboratory supplies and/or medical devices or with commercial providers of medical services.

Thanks

The authors are grateful to the Van Yuzuncu Yil University Scientific Research Projects Council for providing financial assistance of the research (Project number: TSA-2017-6079).

References

Aebi, H. (1965). Methods of Enzymatic Analysis. Editor: Bergmeyer, H.U. New York: Academic Press, Page 673-677.
Akünal Türel, C., & Yunusoğlu, O. (2023). Oleanolic acid suppresses pentylenetetrazole-induced seizure in vivo. International journal of environmental health research, 33(5), 529–540. https://doi.org/10.1080/09603123. 2023.2167947
Aktumsek, A., Zengin, G., Guler, G. O., Cakmak, Y. S., & Duran, A. (2013). Antioxidant potentials and anticholinesterase activities of methanolic and aqueous extracts of three endemic Centaurea L. species. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association, 55, 290–296. https://doi.org/10.1016/j.fct.2013.01.018
Allahverdiyev, O., Dzhafar, S., Berkoz, M., Yildirim, M. (2018). Advances in current medication and new therapeutic approaches in epilepsy. Eastern Journal of Medicine , 23(1), 48 - 59.
Albayrak, S., Sagdic, O., Aksoy, A., & Hamzaoglu, H. (2008). Antimicrobial and antioxidant activities of Helichrysum species from the Mediterranean region of Turkey. Asian Journal of Chemistry, 20(5), 3143–3152.
Antunes Viegas, D., Palmeira-de-Oliveira, A., Salgueiro, L., Martinez-de-Oliveira, J., & Palmeira-de-Oliveira, R. (2014). Helichrysum italicum: from traditional use to scientific data. Journal of ethnopharmacology, 151(1), 54–65. https://doi.org/10.1016/j.jep.2013.11.005
Aslan, M., Orhan, D. D., Orhan, N., Sezik, E., & Yesilada, E. (2007). A study of antidiabetic and antioxidant effects of Helichrysum graveolens capitulums in streptozotocin-induced diabetic rats. Journal of Medicinal Food, 10(2), 396–400. https://doi.org/10.1089/jmf.2006.
Awad, R., Ahmed, F., Bourbonnais-Spear, N., Mullally, M., Ta, C. A., Tang, A., Merali, Z., Maquin, P., Caal, F., Cal, V., Poveda, L., Vindas, P. S., Trudeau, V. L., & Arnason, J. T. (2009). Ethnopharmacology of Q'eqchi' Maya antiepileptic and anxiolytic plants: effects on the GABAergic system. Journal of Ethnopharmacology, 125(2), 257–264. https://doi.org/10.1016/j.jep.2009.06.034

Bakre, A. G., Aderibigbe, A. O., & Ademowo, O. G. (2013). Studies on neuropharmacological profile of ethanol extract of Moringa oleifera leaves in mice. Journal of Ethnopharmacology, 149(3), 783–789. https://doi.org/10.1016/j.jep.2013.08.006
Baytop, T. (1999). Türkiye’de Bitkiler ile Tedavi. Nobel Tıb Kitabevleri, İstanbul.
Berköz, M., Yunusoğlu, O., Aslan, A., & Bozkurt, A. (2024). Investigation of antiepileptic potentials of usnic acid and some lichen species on the behavioral and biochemical levels in pentylenetetrazole-induced kindling model of epilepsy. Journal of Research in Pharmacy. 28(5): 1378-1390. DOI : 10.29228/jrp.816
Büget, B., Türkmen, A. Z., Allahverdiyev, O., & Enginar, N. (2016). Antimuscarinic-induced convulsions in fasted animals after food intake: evaluation of the effects of levetiracetam, topiramate and different doses of atropine. Naunyn-Schmiedeberg's archives of pharmacology, 389(1), 57-62.
Bum, E. N., Schmutz, M., Meyer, C., Rakotonirina, A., Bopelet, M., Portet, C., Jeker, A., Rakotonirina, S. V., Olpe, H. R., & Herrling, P. (2001). Anticonvulsant properties of the methanolic extract of Cyperus articulatus (Cyperaceae). Journal of ethnopharmacology, 76(2), 145–150. https://doi.org/10.1016/s0378-8741(01)00192-1
Collins, M. A., & Neafsey, E. J. (2012). Neuroinflammatory pathways in binge alcohol-induced neuronal degeneration: oxidative stress cascade involving aquaporin, brain edema, and phospholipase A2 activation. Neurotoxicity research, 21(1), 70–78. https://doi.org/10.1007/s12640-011-9276-5
Dai, J., & Mumper, R. J. (2010). Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules (Basel, Switzerland), 15(10), 7313–7352. https://doi.org/10.3390/molecules15107313
Dalar, A., & Konczak, I. (2013). Phenolic contents, antioxidant capacities and inhibitory activities against key metabolic syndrome relevant enzymes of herbal teas from Eastern Anatolia. Industrial Crops and Products, 44, 383-390. https://doi.org/10.1016/j.indcrop.2012.11.037
Dalar, A., Mukemre, M., Unal, M., & Ozgokce, F. (2018). Traditional medicinal plants of Ağrı Province, Turkey. Journal of ethnopharmacology, 226, 56–72. https://doi.org/10.1016/j.jep.2018.08.004
Dalar, A., & Mükemre, M. (2020). Traditional Medicinal Plants of Van Province, Eastern Anatolia. New-York: NOVA Science Publishers Inc.
Dávalos, A., Gómez-Cordovés, C., & Bartolomé, B. (2004). Extending applicability of the oxygen radical absorbance capacity (ORAC-fluorescein) assay. Journal of agricultural and food chemistry, 52(1), 48–54. https://doi.org/10.1021/jf0305231
Davis, P.H., (Ed.) (1975) “Flora of Turkey and the East Aegean Islands” University Press, Edinburg, Vol.5 Dinis, T.C.P, Maderia, V.M.C. & Almeida, M.L.M. (1994). Action of phenolic derivatives (acetaminophen, salicylate, and 5-aminosalicylate) as inhibitors of membrane lipid peroxidation and as peroxyl radical scavengers. Archives of biochemistry and biophysics, 315(1), 161–169. https://doi.org/10.1006/abbi.1994.1485
Doeser, A., Dickhof, G., Reitze, M., Uebachs, M., Schaub, C., Pires, N. M., Bonifácio, M. J., Soares-da-Silva, P., & Beck, H. (2015). Targeting pharmacoresistant epilepsy and epileptogenesis with a dual-purpose antiepileptic drug. Brain : a journal of neurology, 138(Pt 2), 371–387. https://doi.org/10.1093/brain/awu339
Eraković, V., Zupan, G., Varljen, J., & Simonić, A. (2003). Pentylenetetrazol-induced seizures and kindling: changes in free fatty acids, superoxide dismutase, and glutathione peroxidase activity. Neurochemistry international, 42(2), 173–178. https://doi.org/10.1016/s0197-0186(02)00070-0
Ergul Erkec, O., Yunusoglu, O., & Huyut, Z. (2024). Evaluation of repeated ghrelin administration on seizures, oxidative stress and neurochemical parameters in pentyleneterazole induced kindling in rats. The International journal of neuroscience, 134(4), 420–428. https://doi.org/10.1080/00207454.2022.2107516
Eroğlu, H.E., Budak, Ü., Hamazoğlu, E., Aksoy, A., & Albayrak, S. (2010). In vitro cytotoxic effects of methanol extracts of six Helicrysum Taxa used in traditional medicine, Pakistan Journal of Botany, 42(5), 3229-3237.
Ghorbani, A. (2017). Mechanisms of antidiabetic effects of flavonoid rutin. Biomedicine & Pharmacotherapy, 96, 305–312. https://doi.org/10.1016/j.biopha.2017.10.110
Gonçalves, S., Moreira, E., Grosso, C., Andrade, P. B., Valentão, P., & Romano, A. (2017). Phenolic profile, antioxidant activity and enzyme inhibitory activities of extracts from aromatic plants used in Mediterranean diet. Journal of food science and technology, 54(1), 219–227. https://doi.org/10.1007/s13197-016-2453-z
Grabarczyk, M., Justyńska, W., Czpakowska, J., Smolińska, E., Bielenin, A., Glabinski, A., & Szpakowski, P. (2024). Role of Plant Phytochemicals: Resveratrol, Curcumin, Luteolin and Quercetin in Demyelination, Neurodegeneration, and Epilepsy. Antioxidants, 13(11), 1364. https://doi.org/10.3390/antiox13111364
Güven, L., & Gülçin, İ., (2024). Determination of metabolic profiling by LC-MS/MS, evaluation of antioxidant activities, and enzyme inhibition effects of Helichrysum plicatum subsp. pseudopliacatum. KSU J. Agric Nat 27(3), 501-514. https://doi.org/10.18016/ksutarimdoga.vi.1360450
Gwedela, M. N. V., Terai, H., Lampiao, F., Matsunami, K., & Aizawa, H. (2022). Anti-seizure effects of medicinal plants in Malawi on pentylenetetrazole-induced seizures in zebrafish larvae. Journal of Ethnopharmacology, 284, 114763. https://doi.org/10.1016/j.jep.2021.114763
He, X., Chen, X., Yang, Y., Xie, Y., & Liu, Y. (2023). Medicinal plants for epileptic seizures: Phytoconstituents, pharmacology and mechanisms revisited. Journal of Ethnopharmacology, 320, 115995. https://doi.org/10.1016/j.jep.2022.115995
Ilhan, A., Aladag, M. A., Kocer, A., Boluk, A., Gurel, A., & Armutcu, F. (2005). Erdosteine ameliorates PTZ-induced oxidative stress in mice seizure model. Brain research bulletin, 65(6), 495–499. https://doi.org/10.1016/j.brainresbull.2005.02.027
Işık, N., Mükemre, M., Türker, R. S., Zengin, G., & Dalar, A., (2023). Analysis of phytochemical composition and biological activities of Helichrysum pallasii (Sprengel) ledeb leaves. International Journal of Secondary Metabolite, vol. 10, no.1, 71-85. https://doi.org/10.21448/ijsm.1132698
Izol, E., Turhan, M (2024). In-Depth Phytochemical Profile by LC-MS/MS, Mineral Content by ICP-MS, and In-Vitro Antioxidant, Antidiabetic, Antiepilepsy, Anticholinergic, and Antiglaucoma Properties of Bitlis Propolis. Life, 14, 1389. https://doi.org/10.3390/life14111389
Jain S. K. (1989). Hyperglycemia can cause membrane lipid peroxidation and osmotic fragility in human red blood cells. The Journal of biological chemistry, 264(35), 21340–21345.
Kandeda, A. K., Taiwe, G. S., Ayissi, R. E. M., & Moutchida, C. (2021). An aqueous extract of Canarium schweinfurthii attenuates seizures and potentiates sleep in mice: Evidence for involvement of GABA pathway. Biomedicine & Pharmacotherapy, 142, 111973. https://doi.org/10.1016/j.biopha.2021.11197
Kaya, S. (1998). Sayfa 43. Veteriner Hekimliğinde Toksikoloji. Editörler: Kaya, S., Pirinççi, İ., Bilgili, A. Ankara: Medissa Yayınevi.
Kiasalari, Z., Khalili, M., Roghani, M., Heidari, H., & Azizi, Y. (2013). Antiepileptic and Antioxidant Effect of Hydroalcoholic Extract of Ferula assafoetida Gum on Pentylentetrazole- induced Kindling in Male Mice. Basic and clinical neuroscience, 4(4), 299–306.
Koçak, Y., Yunusoglu, O., Huyut, Z. & F. Turkan. (2023). Effects of Artemisinin on Anti-epileptogenic, Antioxidant and Cholinesterase Enzymes in Pentylenetetrazole-induced Kindling Model in Mice. Indian Journal Of Pharmaceutical Education And Research. 57(3s):s821-s830. DOI: 10.5530/ijper.57.3s.93
Kohri, S., Fujii, H., Oowada, S., Endoh, N., Sueishi, Y., Kusakabe, M., Shimmei, M., & Kotake, Y. (2009). An oxygen radical absorbance capacity-like assay that directly quantifies the antioxidant's scavenging capacity against AAPH-derived free radicals. Analytical biochemistry, 386(2), 167–171. https://doi.org/10.1016/j.ab.2008.12.022
Komali, E., Venkataramaiah, C., & Rajendra, W. (2020). Antiepileptic potential of Bacopa monnieri in the rat brain during PTZ-induced epilepsy with reference to cholinergic system and ATPases. Journal of traditional and complementary medicine, 11(2), 137–143. https://doi.org/10.1016/j.jtcme.2020.02.011
Konczak I., Yoshimoto, M., Hou, D. X., Terahara, N., & Yamakawa, O. (2003). Potential chemopreventive properties of anthocyanin-rich aqueous extracts from in vitro produced tissue of sweetpotato (Ipomoea batatas L.). Journal of agricultural and food chemistry, 51(20), 5916–5922. https://doi.org/10.1021/jf030066o
Kumar, R., Arora, R., Sarangi, S. C., Ganeshan, N. S., Agarwal, A., Kaleekal, T., & Gupta, Y. K. (2021). Pharmacodynamic and pharmacokinetic interactions of hydroalcoholic leaf extract of Centella asiatica with valproate and phenytoin in experimental models of epilepsy in rats. Journal of Ethnopharmacology, 270, 113784. https://doi.org/10.1016/j.jep.2021.113784
Liang, N., & Kitts, D. D. (2016). Role of chlorogenic acids in controlling oxidative and inflammatory stress conditions. Nutrients, 8(1), 16. https://doi.org/10.3390/nu8010016
Marchetti, C., Gavazzo, P., Stafford, G. I., & Van Staden, J. (2011). South African plants used in traditional medicine to treat epilepsy have an antagonistic effect on NMDA receptor currents. Journal of ethnopharmacology, 137(1), 382–388. https://doi.org/10.1016/j.jep.2011.05.038
Matthews, D. G., Caruso, M., Alcazar Magana, A., Wright, K. M., Maier, C. S., Stevens, J. F., Gray, N. E., Quinn, J. F., & Soumyanath, A. (2020). Caffeoylquinic acids in Centella asiatica reverse cognitive deficits in male 5XFAD Alzheimer's disease model mice. Nutrients, 12(11), 3488. https://doi.org/10.3390/nu12113488
Mukemre, M., Konczak, I., Uzun, Y. & Dalar, A. (2020). Phytochemical profile and biological activities of Anatolian plantain (Plantago anatolica). Food Bioscience. 36: 100658. DOI: 10.1016/j.fbio.2020.100658
Munguía-Martínez, M. F., Nava-Ruíz, C., Ruíz-Díaz, A., Díaz-Ruíz, A., Yescas-Gómez, P., & Méndez-Armenta, M. (2019). Immunohistochemical Study of Antioxidant Enzymes Regulated by Nrf2 in the Models of Epileptic Seizures (KA and PTZ). Oxidative medicine and cellular longevity, 2019, 1327986. https://doi.org/10.1155/2019/1327986
McCord, J. M., & Fridovich, I. (1969). Superoxide dismutase. Journal of Biological Chemistry, 244 (22), 6049-6055.
Ngoupaye, G. T., Adassi, M. B., Foutsop, A. F., Yassi, F. B., & Ngo Bum, E. (2022). Pentylenetetrazole kindling-induced epilepsy rat models: Insight on the severity state, a comparative study. IBRO neuroscience reports, 13, 164–176. https://doi.org/10.1016/j.ibneur.2022.08.003
Obay, B. D., Taşdemir, E., Tümer, C., Bilgin, H., & Atmaca, M. (2008). Dose dependent effects of ghrelin on pentylenetetrazole-induced oxidative stress in a rat seizure model. Peptides, 29(3), 448–455. https://doi.org/10.1016/j.peptides.2007.11.020
Ou, B., Hampsch-Woodill, M., & Prior, R.L. (2001). Development and validation of an improved oxygen radical absorbance capacity assay using fluorescein as the fluorescent probe. Journal of Agricultural and Food Chemistry, 49, 4619–26.
O'Toole, S., Benson, A., Lambert, V., Gallagher, P., Shahwan, A., & Austin, J. K. (2015). Family communication in the context of pediatric epilepsy: A systematic review. Epilepsy & behavior: E&B, 51, 225–239. https://doi.org/10.1016/j.yebeh.2015.06.043
Paglia, D. E., & Valentine, W. N. (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. The Journal of laboratory and clinical medicine, 70(1), 158–169.
Pale, S., Neteydji, S., Taiwe, G. S., Kouemou Emegam, N., & Bum, E. N. (2022). Anticonvulsant effects of Cymbopogon giganteus extracts with possible effects on fully kindled seizures and anxiety in experimental rodent model of mesio-temporal epilepsy induced by pilocarpine. Journal of Ethnopharmacology, 286, 114863. https://doi.org/10.1016/j.jep.2021.114863
Pasayeva, L., Yetimoğlu, S., Fatullayev, H., İnce, U., Bozkurt, N. M., & Karaboğa Arslan, A. K. (2025). Optimizing health benefits of walnut (Juglans regia L.) agricultural by products: Impact of maceration and Soxhlet extraction methods on phytochemical composition, enzyme inhibition, antioxidant, antimicrobial, and cytotoxic activities. Food Bioscience, 64, 105923. doi:10.1016/j.fbio.2025.105923
Pi, X., Lee, J., Li, F., & Rosenberg, H. C. (2004). Decreased expression of brain cAMP response element-binding protein gene following pentylenetetrazol seizure. Brain research. Molecular brain research, 127(1-2), 60–67. s: http//doi.org/10.1016/j.molbrainres.2004.05.006
Pharmacopoeia, C. (2020). Pharmacopoeia of the People’s Republic of China. Medical Science and Technology Press: Beijing, China, 340-342.
Prior, R.L. (2015). Oxygen radical absorbance capacity (ORAC): New horizons in relating dietary antioxidants/bioactives and health benefits. Journal of Functional Foods, 18, 797-810. https://doi.org/10.1016/j.jff.2014.12.01
Rahmati, B., Khalili, M., Roghani, M., & Ahghari, P. (2013). Anti-epileptogenic and antioxidant effect of Lavandula officinalis aerial part extract against pentylenetetrazol-induced kindling in male mice. Journal of ethnopharmacology, 148(1), 152–157. https://doi.org/10.1016/j.jep.2013.04.004
Rivera, D., Alcaraz, F., Verde, A., Fajardo, J., & Obón, C. (2008). Las plantas en la cultura popular. In Enciclopedia divulgativa de la historia natural de Jumilla-Yecla (pp. 435–447). Sociedad Mediterránea de Historia Natural.
Rubio, C., Rubio-Osornio, M., Retana-Márquez, S., Verónica Custodio, M. L., & Paz, C. (2010). In vivo experimental models of epilepsy. Central nervous system agents in medicinal chemistry, 10(4), 298–309. https://doi.org/10.2174/187152410793429746
Sala, A. (2001). Principios antiinflamatorios y antioxidantes de Helichrysum italicum (Roth) G. Don (Doctoral dissertation, University of Valencia, Valencia).
Shahi, S., Ahmadian, E., Fathi, N., Eftekhari, A., Khalilov, R., & Dizaj, S. M. (2019). Preparation and physicochemical assessment of rutin-loaded gelatin nanoparticles. Journal of Advanced Chemical and Pharmaceutical Materials (JACPM), 2(2), 138–142
Sharifi-Rad, J., Quispe, C., Herrera-Bravo, J., Martorell, M., Sharopov, F., Tumer, T. B., ... & Calina, D. (2021). A pharmacological perspective on plant-derived bioactive molecules for epilepsy. Neurochemical Research,46(9), 2205-2225.
Singh, R., Sarangi, S. C., Singh, S., & Tripathi, M. (2022). A review on role of metformin as a potential drug for epilepsy treatment and modulation of epileptogenesis. Seizure, 101, 253–261. https://doi.org/10.1016/j.seizure.2022.09.003
Süzgeç, S., Meriçli, A. H., Houghton, P. J., & Cubukçu, B. (2005). Flavonoids of Helichrysum compactum and their antioxidant and antibacterial activity. Fitoterapia, 76(2), 269–272. https://doi.org/10.1016/j.fitote.2004.12.006
Sucher, N. J., & Carles, M. C. (2015). A pharmacological basis of herbal medicines for epilepsy. Epilepsy & behavior: E&B, 52(Pt B), 308–318. https://doi.org/10.1016/j.yebeh.2015.05.012
Stafford, G. I., Jäger, A. K., & van Staden, J. (2005). Activity of traditional South African sedative and potentially CNS-acting plants in the GABA-benzodiazepine receptor assay. Journal of ethnopharmacology, 100(1-2), 210–215. https://doi.org/10.1016/j.jep.2005.04.004
Stafford, G. I., Pedersen, M. E., van Staden, J., & Jäger, A. K. (2008). Review on plants with CNS-effects used in traditional South African medicine against mental diseases. Journal of ethnopharmacology, 119(3), 513–537. https://doi.org/10.1016/j.jep.2008.08.010
Stafstrom, C. E., & Carmant, L. (2015). Seizures and epilepsy: an overview for neuroscientists Cold Spring Harbor perspectives in medicine, 5(6), a022426. https://doi.org/10.1101/cshperspect.a022426
Svalheim, S., Sveberg, L., Mochol, M., & Taubøll, E. (2015). Interactions between antiepileptic drugs and hormones. Seizure, 28, 12–17. https://doi.org/10.1016/j.seizure.2015.02.022
Tan, A. C., Konczak, I., Sze, D. M., & Ramzan, I. (2010). Towards the discovery of novel phytochemicals for disease prevention from native Australian plants: an ethnobotanical approach. Asia Pacific journal of clinical nutrition, 19(3), 330–334.
Taspinar, N., Hacimuftuoglu, A., Butuner, S., Togar, B., Arslan, G., Taghizadehghalehjoughi, A., Okkay, U., Agar, E., Stephens, R., Jr, Turkez, H., & Abd El-Aty, A. M. (2021). Differential effects of inhibitors of PTZ-induced kindling on glutamate transporters and enzyme expression. Clinical and experimental pharmacology & physiology, 48(12), 1662–1673. https://doi.org/10.1111/1440-1681.13575
Tavakoli, Z., Tahmasebi Dehkordi, H., Lorigooini, Z., Rahimi-Madiseh, M., Korani, M. S., & Amini-Khoei, H. (2023). Anticonvulsant effect of quercetin in pentylenetetrazole (PTZ)-induced seizures in male mice: The role of anti-neuroinflammatory and antioxidative stress. International Immunopharmacology, 116, 109772. https://doi.org/10.1016/j.intimp.2023.109772
Torres, A., Noriega, L. G., Delgadillo-Puga, C., Tovar, A. R., & Navarro-Ocaña, A. (2021). Caffeoylquinic acid derivatives of purple sweet potato as modulators of mitochondrial function in mouse primary hepatocytes. Molecules, 26(2), 319. https://doi.org/10.3390/molecules26020319
Uğur, Y., & Güzel, A., (2025). Phenolic Profile and Antioxidant Capacity of Helichrysum arenarium Extracts: A Comprehensive LC-MS/MS and Antioxidant Analysis. KSU J. Agric Nat 28 (1), 1-8. DOI: 10.18016/ ksutarimdoga.vi.1545680.
Wu, J., Cao, M. Y. J., Peng, Y., Dong, B. H., Jiang, Y. X., Hu, C. J., Zhu, P. J., Xing, W. D., Yu, L. Y., Xu, R. C., & Chen, Z. M. (2023). Research progress on the treatment of epilepsy with traditional Chinese medicine. Phytomedicine, 120, 155022. https://doi.org/10.1016/j.phymed.2023.155022
Xie, Y. L., Yang, Y., Yuan, X. F., Liu, Y. J., & He, X. R. (2023). Herb pair of Polygala tenuifolia Willd and Acorus tatarinowii Schott decoction attenuates seizures and alleviates anxiety in mice: Evidence for modulating inflammation, alleviating oxidative stress and mediating GABA pathway. Pakistan Journal of Pharmaceutical Sciences, 36(2), 565–577. https://doi.org/10.36721/PJPS.2323.36.2.REG.565-57
Viegas, D. A., Oliveira, A. P., Salgueiro, L., Oliveira, J. M., & Oliveira, R. M. (2014). Helichrysum italicum: From traditional use to scientific data. Journal of Ethnopharmacology, 151(1), 54–65. https://doi.org/10.1016/j.jep.2013.10.056
Yurt, B., Sağlamtaş, R., Demir, Y., İzol, E., Diril, H., Çağlayan, C (2024). Determination of In Vitro Antioxidant, Anticholinergic and Antiepileptic Activities of some Medicinal and Aromatic Plant Extracts. Kahramanmaraş Sütçü İmam Üniversitesi Tarım ve Doğa Dergisi, 27 (Suppl. 1), 1-15. https://doi.org/10.18016/ksutarimdoga.vi.1472403
Yunusoglu, O., Kalfa, I., Demirel, M. E., Binzet, M. A., Sevinc, U. Z., Turel, I., & Kurt, A. H. (2025). A comprehensive review of the pharmacological, therapeutic, and toxicological properties of boric acid and other boron-containing compounds: Current landscape and future perspectives. Pharmacy & Pharmacology Journal, 13(3), 202–238. https://doi.org/10.19163/2307-9266-2025-13-3-202-238
Zhang, S. H., Liu, D., Hu, Q., Zhu, J., Wang, S., & Zhou, S. (2019). Ferulic acid ameliorates pentylenetetrazol-induced seizures by reducing neuron cell death. Epilepsy research, 156, 106183. https://doi.org/10.1016/j.eplepsyres.2019.106183
Zheng, Z., Zhang, X., Liu, J., He, P., Zhang, S., Zhang, Y., Gao, J., Yang, S., Kang, N., Afridi, M. I., Gao, S., Chen, C., & Tu, H. (2021). GABAergic synapses suppress intestinal innate immunity via insulin signaling in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America, 118(20), e2021063118. https://doi.org/10.1073/pnas.2021063118

Details

Primary Language

English

Subjects

Plant Biochemistry , Pharmaceutical Botany

Journal Section

Research Article

Authors

Oruç Yunusoğlu ^*
0000-0003-1075-9574
Türkiye

Muzaffer Mukemre
0000-0002-0544-7157
Türkiye

Rabia Sena Dalkılıç
0000-0002-2017-7159
Türkiye

Early Pub Date

October 18, 2025

Publication Date

January 1, 2026

Submission Date

May 14, 2025

Acceptance Date

August 7, 2025

Published in Issue

Year 2026 Volume: 29 Number: 1

DOI

https://doi.org/10.18016/ksutarimdoga.vi.1676615

IZ

https://izlik.org/JA86RB77PD

Cite

RIS / Bibtex

APA

Yunusoğlu, O., Mukemre, M., & Dalkılıç, R. S. (2026). Investigation of the Phytochemical Components and Antiepileptic Potential of Helichrysum pallasii (Sprengel) Ledeb. Through in vitro and in vivo Studies. Kahramanmaraş Sütçü İmam Üniversitesi Tarım Ve Doğa Dergisi, 29(1), 15-39. https://doi.org/10.18016/ksutarimdoga.vi.1676615