Effects of a crude extract of Echinops mosulensis on an induced Parkinson's disease model in mice
Authors/Creators
- 1. Al-Nahrain University, Baghdad, Iraq
Description
Parkinson's disease (PD) is the second most widespread chronic, progressive neurodegenerative disease after Alzheimer's disease. Key mechanisms contributing to PD development are oxidative stress, inflammation, protein misfolding and aggregation, apoptotic cell death, excitotoxicity, mitochondrial dysfunction, and loss of trophic support. We aimed to investigate the neuroprotective effect of a crude extract of Iraqi Echinops mosulensis on an induced PD model in mice. Forty male Swiss Albino mice were divided into four groups of ten mice; the negative control received distilled water orally, and the induction group received 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg/day) intraperitoneally (IP). The positive control group was administered pramipexole orally (1 mg/kg/day), and the final group received a crude extract of E. mosulensis orally (250 mg/kg/day). The experimental phase lasted for 25 days for all studied groups. On day 26, the behavior test was done, and on day 27, all animals were sacrificed. Homogenized brain tissue was prepared for analysis. Treatment with crude extract significantly reduced MDA, IL-6, IL-1 beta, caspase 3, cytochrome C, and alpha-synuclein levels compared to the induction group, while dopamine (DA) significantly increased. In addition, the catalepsy test was significantly reduced in the E. mosulensis group compared to the induction group. In conclusion, the crude extract of E. mosulensis exerts neuroprotective effects through multiple mechanisms, and it offers opportunities for developing a novel therapeutic method for treating PD.
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References
- Abdulmohsin H, Raghif A, Manna MJ (2019) The protective effects of Echinops heterophyllus extract against methotrexate-induced hepatotoxicity in rabbits. Asian Journal of Pharmaceutical and Clinical Research 12: 384–390. https://doi.org/10.22159/ajpcr.2019.v12i1.30213
- Airavaara M, Harvey BK, Voutilainen MH, Shen H, Chou J, Lindholm P, Lindahl M, Tuominen RK, Saarma M, Hoffer B, Wang Y (2012) CDNF protects the nigrostriatal dopamine system and promotes recovery after MPTP treatment in mice. Cell Transplant 21: 1213–1223. https://doi.org/10.3727/096368911X600948
- Ait Lhaj Z, Ibork H, El Idrissi S, Ait Lhaj F, Sobeh M, Mohamed WMY, Alamy M, Taghzouti K, Abboussi O (2023) Bioactive strawberry fruit (Arbutus unedo L.) extract remedies paraquat-induced neurotoxicity in the offspring prenatally exposed rats. Front Neurosci 17: 1244603. https://doi.org/10.3389/fnins.2023.1244603
- Aktas B (2023) Gut Microbial Alteration in MPTP Mouse Model of Parkinson Disease is Administration Regimen Dependent. Cellular and Molecular Neurobiology 43: 2815–2829. https://doi.org/10.1007/s10571-023-01319-7
- Alizzi FJ, Showman HAK, Fawzi HA (2018) Levonorgestrel-releasing intrauterine system in adenomyosis; predictors for response and clinical outcome. Asian Journal of Pharmaceutical and Clinical Research 11: 214–217. https://doi.org/10.22159/ajpcr.2018.v11i12.27109
- Alkhazragy B, Alshawi NN (2023) Protective effect of cranberry extract against cisplatin-induced nephrotoxicity by improving oxidative stress in mice. Iraqi Journal of Pharmaceutical Sciences (P-ISSN 1683-3597 E-ISSN 2521-3512) 32: 112–119. https://doi.org/10.31351/vol32iss2pp112-119
- Ardah MT, Bharathan G, Kitada T, Haque ME (2020) Ellagic acid prevents dopamine neuron degeneration from oxidative stress and neuroinflammation in MPTP model of Parkinson's disease. Biomolecules 10(11): 1519 https://doi.org/10.3390/biom10111519
- Arega M, Nardos A, Debella A, Dereje B, Terefe L, Abebe A (2023) Evaluation of anti-inflammatory activity of the methanol extracts of Premna schimperi Engl (Lamiaceae) leaves in rats. Journal of Experimental Pharmacology 15: 437–447. https://doi.org/10.2147/JEP.S432615
- Atiq A, Lee HJ, Khan A, Kang MH, Rehman IU, Ahmad R, Tahir M, Ali J, Choe K, Park JS, Kim MO (2023) Vitamin E analog trolox attenuates MPTP-induced Parkinson's disease in mice, mitigating oxidative stress, neuroinflammation, and motor impairment. International Journal of Molecular Sciences 24(12): 9942. https://doi.org/10.3390/ijms24129942
- Azimullah S, Meeran MFN, Ayoob K, Arunachalam S, Ojha S, Beiram R (2023) Tannic acid mitigates rotenone-induced dopaminergic neurodegeneration by inhibiting inflammation, oxidative stress, apoptosis, and glutamate toxicity in rats. International Journal of Molecular Sciences 24(12): 9876. https://doi.org/10.3390/ijms24129876
- Behl T, Kaur G, Sehgal A, Zengin G, Singh S, Ahmadi A, Bungau S (2022) Flavonoids, the family of plant-derived antioxidants making inroads into novel therapeutic design against ionizing radiation-induced oxidative stress in Parkinson's disease. Current Neuropharmacology 20: 324–343. https://doi.org/10.2174/1570159X19666210524152817
- Bitew H, Hymete A (2019) The genus Echinops: phytochemistry and biological activities: a review. Frontiers in Pharmacology 10: 1234. https://doi.org/10.3389/fphar.2019.01234
- Burré J (2015) The synaptic function of α-synuclein. Journal of Parkinson's Disease 5: 699–713. https://doi.org/10.3233/JPD-150642
- Campolo M, Casili G, Biundo F, Crupi R, Cordaro M, Cuzzocrea S, Esposito E (2017) The neuroprotective effect of dimethyl fumarate in an MPTP-mouse model of Parkinson's disease: Involvement of reactive oxygen species/nuclear factor-κb/nuclear transcription factor related to NF-E2. Antioxid Redox Signal 27: 453–471. https://doi.org/10.1089/ars.2016.6800
- Chau KY, Cooper JM, Schapira AH (2013) Pramipexole reduces phosphorylation of α-synuclein at serine-129. Journal of Molecular Neuroscience 51: 573–580. https://doi.org/10.1007/s12031-013-0030-8
- Chen Y-F, Yang C-H, Chang M-S, Ciou Y-P, Huang Y-C (2010) Foam properties and detergent abilities of the saponins from Camellia oleifera. International Journal of Molecular Sciences 11: 4417–4425. https://doi.org/10.3390/ijms11114417
- Chia SJ, Tan EK, Chao YX (2020) Historical perspective: models of Parkinson's disease. International Journal of Molecular Sciences 21(7): 2464. https://doi.org/10.3390/ijms21072464
- Chung KT, Wong TY, Wei CI, Huang YW, Lin Y (1998) Tannins and human health: a review. Critical Reviews in Food Science and Nutrition 38: 421–464. https://doi.org/10.1080/10408699891274273
- Cuenca-Bermejo L, Pizzichini E, Gonçalves VC, Guillén-Díaz M, Aguilar-Moñino E, Sánchez-Rodrigo C, González-Cuello AM, Fernández-Villalba E, Herrero MT (2021) A new tool to study parkinsonism in the context of aging: MPTP intoxication in a natural model of multimorbidity. International Journal of Molecular Sciences 22(9): 4341. https://doi.org/10.3390/ijms22094341
- Daniels MJ, Nourse JB, Kim H, Sainati V, Schiavina M, Murrali MG, Pan B, Ferrie JJ, Haney CM, Moons R, Gould NS, Natalello A, Grandori R, Sobott F, Petersson EJ, Rhoades E, Pierattelli R, Felli I, Uversky VN, Caldwell KA, Caldwell GA, Krol ES, Ischiropoulos H (2019) Cyclized NDGA modifies dynamic α-synuclein monomers preventing aggregation and toxicity. Scientific Reports 9: 2937. https://doi.org/10.1038/s41598-019-39480-z
- Dantas CG, da Paixão AO, Nunes TLGM, Silva IJF, dos S. Lima B, Araújo AAS, de Albuquerque-Junior RLC, Gramacho KP, Padilha FF, da Costa LP, Severino P, Cardoso JC, Souto EB, Gomes MZ (2022) Africanized Bee Venom (Apis mellifera Linnaeus): Neuroprotective Effects in a Parkinson's Disease Mouse Model Induced by 6-hydroxydopamine. Toxics 10: 583. https://doi.org/10.3390/toxics10100583
- Díaz HS, Ríos-Gallardo A, Ortolani D, Díaz-Jara E, Flores MJ, Vera I, Monasterio A, Ortiz FC, Brossard N, Osorio F, Río RD (2022) Lipid-encapsuled grape tannins prevent oxidative-stress-induced neuronal cell death, intracellular ROS accumulation and inflammation. Antioxidants (Basel) 11(10): 1928. https://doi.org/10.3390/antiox11101928
- Elbassuoni EA, Ahmed RF (2019) Mechanism of the neuroprotective effect of GLP-1 in a rat model of Parkinson's with pre-existing diabetes. Neurochemistry International 131: 104583. https://doi.org/10.1016/j.neuint.2019.104583
- Elhak SG, Ghanem AA, Abdelghaffar H, Eldakroury S, Eltantawy D, Eldosouky S, Salama M (2010) The role of pramipexole in a severe Parkinson's disease model in mice. Therapeutic Advances in Neurological Disorders 3: 333–337. https://doi.org/10.1177/1756285610389655
- Eram S, Ahmad M, Arshad S (2013) Experimental evaluation of Echinops echinatus as an effective hepatoprotective. Scientific Research and Essays 8: 1919–1923.
- Frederick K, Patel RC (2023) Luteolin protects DYT-PRKRA cells from apoptosis by suppressing PKR activation. Frontiers in Pharmacology 14: 1118725. https://doi.org/10.3389/fphar.2023.1118725
- Haque ME, Azam S, Akther M, Cho DY, Kim IS, Choi DK (2021) The neuroprotective effects of GPR4 inhibition through the attenuation of caspase mediated apoptotic cell death in an MPTP induced mouse model of Parkinson's disease. International Journal of Molecular Sciences 22(9): 4674. https://doi.org/10.3390/ijms22094674
- Harborne A (1998) Phytochemical Methods A Guide To Modern Techniques Of Plant Analysis. Springer Science & Business Media. Springer Dordrecht, 302 pp.
- Harborne J, Harborne J (1973) The terpenoids. Phytochemical Methods: A Guide to Modern Techniques of Plant Analysis, 89–131. https://doi.org/10.1007/978-94-009-5921-7_3
- Hassan RF, Kadhim HM (2022) Exploring the role of phenolic extract as an ointment dosage form in inducing wound healing in mice. Journal of Pharmaceutical Negative Results 13: 186–193. https://doi.org/10.47750/pnr.2022.13.03.030
- Heng Y, Li YY, Wen L, Yan JQ, Chen NH, Yuan YH (2022) Gastric enteric glial cells: a new contributor to the synucleinopathies in the MPTP-induced Parkinsonism mouse. Molecules 27(21): 7414. https://doi.org/10.3390/molecules27217414
- Hsieh MH, Gu SL, Ho SC, Pawlak CR, Lin CL, Ho YJ, Lai TJ, Wu FY (2012) Effects of MK-801 on recognition and neurodegeneration in an MPTP-induced Parkinson's rat model. Behavioural Brain Research 229: 41–47. https://doi.org/10.1016/j.bbr.2011.12.035
- Hu LW, Yen JH, Shen YT, Wu KY, Wu MJ (2014) Luteolin modulates 6-hydroxydopamine-induced transcriptional changes of stress response pathways in PC12 cells. PLoS ONE 9: e97880. https://doi.org/10.1371/journal.pone.0097880
- Hu M, Li F, Wang W (2018) Vitexin protects dopaminergic neurons in MPTP-induced Parkinson's disease through PI3K/Akt signaling pathway. Drug Design, Development and Therapy 12: 565–573. https://doi.org/10.2147/DDDT.S156920
- Hussein ZA, Abu-Raghif AR, Fawzi HA (2024a) The mitigating effect of para-hydroxycinnamic acid in bleomycin-induced pulmonary fibrosis in mice through targeting oxidative, inflammatory and fibrotic pathways. Basic & Clinical Pharmacology & Toxicology 135: 23–42. https://doi.org/10.1111/bcpt.14018
- Hussein ZA, Abu-Raghif AR, Tahseen NJ, Rashed KA, Shaker NS, Fawzi HA (2024b) Vinpocetine alleviated alveolar epithelial cells injury in experimental pulmonary fibrosis by targeting PPAR-γ/NLRP3/NF-κB and TGF-β1/Smad2/3 pathways. Scientific Reports 14(1): 11131. https://doi.org/10.1038/s41598-024-61269-y
- Jackson Seukep A, Zhang YL, Xu YB, Guo MQ (2020) In vitro antibacterial and antiproliferative potential of Echinops lanceolatus Mattf. (Asteraceae) and identification of potential bioactive compounds. Pharmaceuticals (Basel) 13(4): 59. https://doi.org/10.3390/ph13040059
- Khadim EJ, Abdulrasool AA, Awad ZJ (2014) Phytochemical investigation of alkaloids in the Iraqi Echinops heterophyllus (Compositae). Iraqi Journal of Pharmaceutical Sciences 23: 26–34. https://doi.org/10.31351/vol23iss1pp26-34
- Khan MM, Raza SS, Javed H, Ahmad A, Khan A, Islam F, Safhi MM, Islam F (2012) Rutin protects dopaminergic neurons from oxidative stress in an animal model of Parkinson's disease. Neurotoxicity Research 22: 1–15. https://doi.org/10.1007/s12640-011-9295-2
- Khan S, Al-Qurainy F, Al-Hashimi A, Nadeem M, Tarroum M, Shaikhaldein HO, Salih AM (2023) Effect of Green Synthesized ZnO-NPs on Growth, Antioxidant System Response and Bioactive Compound Accumulation in Echinops macrochaetus, a Potential Medicinal Plant, and Assessment of Genome Size (2C DNA Content). Plants (Basel) 12(8): 1669. https://doi.org/10.3390/plants12081669
- Koga S, Sekiya H, Kondru N, Ross OA, Dickson DW (2021) Neuropathology and molecular diagnosis of Synucleinopathies. Molecular Neurodegeneration 16: 83. https://doi.org/10.1186/s13024-021-00501-z
- Kouhestani S, Jafari A, Babaei P (2018) Kaempferol attenuates cognitive deficit via regulating oxidative stress and neuroinflammation in an ovariectomized rat model of sporadic dementia. Neural Regeneration Research 13: 1827–1832. https://doi.org/10.4103/1673-5374.238714
- Koziorowski D, Figura M, Milanowski Ł M, Szlufik S, Alster P, Madetko N, Friedman A (2021) Mechanisms of Neurodegeneration in Various Forms of Parkinsonism-Similarities and Differences. Cells 10(3): 656. https://doi.org/10.3390/cells10030656
- Liu L, Peritore C, Ginsberg J, Shih J, Arun S, Donmez G (2015) Protective role of SIRT5 against motor deficit and dopaminergic degeneration in MPTP-induced mice model of Parkinson's disease. Behavioural Brain Research 281: 215–221. https://doi.org/10.1016/j.bbr.2014.12.035
- Lorente-Picón M, Laguna A (2021) New Avenues for Parkinson's Disease Therapeutics: Disease-Modifying Strategies Based on the Gut Microbiota. Biomolecules 11: 433. https://doi.org/10.3390/biom11030433
- Ma Y, Rong Q (2022) Effect of different MPTP administration intervals on mouse models of Parkinson's disease. Contrast Media & Molecular Imaging 2022: 2112146. https://doi.org/10.1155/2022/2112146
- Magalingam KB, Radhakrishnan AK, Haleagrahara N (2015) Protective mechanisms of flavonoids in Parkinson's disease. Oxidative Medicine and Cellular Longevity 2015: 314560. https://doi.org/10.1155/2015/314560
- Mahmood AAR, Khadeem EJ (2013) Phytochemical investigation of flavonoids glycoside in the Iraqi Echinops heterophyllus (Compositae). Pharmacie Globale 4: 1.
- Mailoa MN, Mahendradatta M, Laga A, Djide N (2013) Tannin extract of guava leaves (Psidium guajava L) variation with concentration organic solvents. International Journal of Scientific and Technology Research 2: 106–110.
- Maurya SK, Kushwaha AK, Seth A (2015) Ethnomedicinal review of Usnakantaka (Echinops echinatus Roxb.). Pharmacognosy Reviews 9: 149–154. https://doi.org/10.4103/0973-7847.162138
- Mbiydzenyuy NE, Ninsiima HI, Valladares MB, Pieme CA (2018) Zinc and linoleic acid pre-treatment attenuates biochemical and histological changes in the midbrain of rats with rotenone-induced Parkinsonism. BMC Neuroscience 19: 29. https://doi.org/10.1186/s12868-018-0429-9
- Mohammed SS, Kadhim HM, AL-Sudani IM, Musatafa WW (2022) Anti-inflammatory effects of topically applied azilsartan in a mouse model of imiquimod-induced psoriasis. International Journal of Drug Delivery Technology 3: 1249–1255. https://doi.org/10.25258/ijddt.12.3.53
- Mor DE, Daniels MJ, Ischiropoulos H (2019) The usual suspects, dopamine and alpha-synuclein, conspire to cause neurodegeneration. Movement Disorders 34: 167–179. https://doi.org/10.1002/mds.27607
- Moraes LS, Rohor BZ, Areal LB, Pereira EV, Santos AM, Facundo VA, Santos AR, Pires RG, Martins-Silva C (2016) Medicinal plant Combretum leprosum mart ameliorates motor, biochemical and molecular alterations in a Parkinson's disease model induced by MPTP. Journal of Ethnopharmacology 185: 68–76. https://doi.org/10.1016/j.jep.2016.03.041
- Nath M, Chakravorty M, Chowdhury S (1946) Liebermann-Burchard reaction for steroids. Nature 157: 103–104. https://doi.org/10.1038/157103b0
- Nikokalam Nazif N, Khosravi M, Ahmadi R, Bananej M, Majd A (2020) Effect of treadmill exercise on catalepsy and the expression of the BDNF gene in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine -induced Parkinson in male NMRI mice. Iranian Journal of Basic Medical Sciences 23: 483–493.
- Nimmo JT, Verma A, Dodart JC, Wang CY, Savistchenko J, Melki R, Carare RO, Nicoll JAR (2020) Novel antibodies detect additional α-synuclein pathology in synucleinopathies: potential development for immunotherapy. Alzheimer's Research & Therapy12: 159. https://doi.org/10.1186/s13195-020-00727-x
- Obaid KA, Fawzi HA (2024) Evaluation of empagliflozin efficacy as a promising anti-aging treatment in mice: In-vivo study. Pharmacia 71: 1–9. https://doi.org/10.3897/pharmacia.71.e116184
- Ogunruku OO, Ogunyemi BO, Oboh G, Babatunde OO, Boligon AA (2019) Modulation of dopamine metabolizing enzymes and antioxidant status by Capsicum annuum Lin in rotenone-intoxicated rat brain. Toxicology Reports 6: 795–802. https://doi.org/10.1016/j.toxrep.2019.07.012
- Pariyar R, Bastola T, Lee DH, Seo J (2022) Neuroprotective Effects of the DPP4 Inhibitor Vildagliptin in In Vivo and In Vitro Models of Parkinson's Disease. International journal of molecular sciences 23(4): 2388. https://doi.org/10.3390/ijms23042388
- Radovanović B, Mladenović J, Radovanović A, Pavlović R, Nikolić V (2015) Phenolic composition, antioxidant, antimicrobial and cytotoxic activites of Allium porrum L.(Serbia) extracts. Journal of Food and Nutrition Research 3: 564–569.
- Rai SN, Birla H, Singh SS, Zahra W, Patil RR, Jadhav JP, Gedda MR, Singh SP (2017) Mucuna pruriens Protects against MPTP Intoxicated Neuroinflammation in Parkinson's Disease through NF-κB/pAKT Signaling Pathways. Frontiers in Aging Neuroscience 9: 421. https://doi.org/10.3389/fnagi.2017.00421
- Rezaei M, Alirezaei M (2014) Protective effects of Althaea officinalis L. extract in 6-hydroxydopamine-induced hemi-Parkinsonism model: behavioral, biochemical and histochemical evidence. The Journal of Physiological Sciences 64: 171–176. https://doi.org/10.1007/s12576-014-0305-z
- Romero-Fernandez W, Taura JJ, Crans RAJ, Lopez-Cano M, Fores-Pons R, Narváez M, Carlsson J, Ciruela F, Fuxe K, Borroto-Escuela DO (2022) The mGlu(5) receptor protomer-mediated dopamine D(2) receptor trans-inhibition is dependent on the adenosine A(2A) Receptor Protomer: implications for Parkinson's disease. Molecular Neurobiology 59: 5955–5969. https://doi.org/10.1007/s12035-022-02946-9
- Saadullah M, Arif S, Hussain L, Asif M, Khurshid U (2022) Dose Dependent effects of Breynia cernua against the paraquat induced parkinsonism like symptoms in animals' model: in vitro, in vivo and mechanistic studies. Dose Response 20: 15593258221125478. https://doi.org/10.1177/15593258221125478
- Saeed U, Compagnone J, Aviv RI, Strafella AP, Black SE, Lang AE, Masellis M (2017) Imaging biomarkers in Parkinson's disease and Parkinsonian syndromes: current and emerging concepts. Transl Neurodegener 6: 8. https://doi.org/10.1186/s40035-017-0076-6
- Saleem U, Hussain L, Shahid F, Anwar F, Chauhdary Z, Zafar A (2022) Pharmacological potential of the standardized methanolic extract of Prunus armeniaca L. in the haloperidol-induced Parkinsonism rat model. Evidence-Based Complementary and Alternative Medicine 2022: 3697522. https://doi.org/10.1155/2022/3697522
- San Miguel M, Martin KL, Stone J, Johnstone DM (2019) Photobiomodulation mitigates cerebrovascular leakage induced by the Parkinsonian neurotoxin MPTP. Biomolecules 9(10): 564. https://doi.org/10.3390/biom9100564
- Shah MD, Hossain MA (2014) Total flavonoids content and biochemical screening of the leaves of tropical endemic medicinal plant Merremia borneensis. Arabian Journal of Chemistry 7: 1034–1038. https://doi.org/10.1016/j.arabjc.2010.12.033
- Shen XL, Song N, Du XX, Li Y, Xie JX, Jiang H (2017) Nesfatin-1 protects dopaminergic neurons against MPP(+)/MPTP-induced neurotoxicity through the C-Raf-ERK1/2-dependent anti-apoptotic pathway. Scientific Reports 7: 40961. https://doi.org/10.1038/srep40961
- Thadathil N, Xiao J, Hori R, Alway SE, Khan MM (2021) Brain selective estrogen treatment protects dopaminergic neurons and preserves behavioral function in MPTP-induced mouse model of Parkinson's Disease. Journal of Neuroimmune Pharmacology 16: 667–678. https://doi.org/10.1007/s11481-020-09972-1
- Tolosa E, Garrido A, Scholz SW, Poewe W (2021) Challenges in the diagnosis of Parkinson's disease. The Lancet Neurology 20: 385–397. https://doi.org/10.1016/S1474-4422(21)00030-2
- Underwood W, Anthony R (2020) AVMA guidelines for the euthanasia of animals: 2020 edition. 2020-2021.
- Vajdi-Hokmabad R, Ziaee M, Sadigh-Eteghad S, Sandoghchian Shotorbani S, Mahmoudi J (2017) Modafinil improves catalepsy in a rat 6-hydroxydopamine model of Parkinson's disease; possible involvement of dopaminergic neurotransmission. Advanced Pharmaceutical Bulletin 7: 359–365. https://doi.org/10.15171/apb.2017.043
- Wang WW, Han R, He HJ, Li J, Chen SY, Gu Y, Xie C (2021) Administration of quercetin improves mitochondria quality control and protects the neurons in 6-OHDA-lesioned Parkinson's disease models. Aging (Albany NY) 13: 11738–11751. https://doi.org/10.18632/aging.202868
- Yahfoufi N, Alsadi N, Jambi M, Matar C (2018) The Immunomodulatory and Anti-Inflammatory Role of Polyphenols. Nutrients 10(11): 1618. https://doi.org/10.3390/nu10111618
- Yimer T, Birru EM, Adugna M, Geta M, Emiru YK (2020) Evaluation of analgesic and anti-inflammatory activities of 80% methanol root extract of Echinops kebericho M. (Asteraceae). Journal of Inflammation Research 13: 647–658. https://doi.org/10.2147/JIR.S267154
- Zahedipour F, Hosseini SA, Henney NC, Barreto GE, Sahebkar A (2022) Phytochemicals as inhibitors of tumor necrosis factor alpha and neuroinflammatory responses in neurodegenerative diseases. Neural Regeneration Research 17: 1675–1684. https://doi.org/10.4103/1673-5374.332128
- Zhang QS, Heng Y, Mou Z, Huang JY, Yuan YH, Chen NH (2017) Reassessment of subacute MPTP-treated mice as animal model of Parkinson's disease. Acta Pharmacologica Sinica 38: 1317–1328. https://doi.org/10.1038/aps.2017.49
- Zhao-Shea R, Cohen BN, Just H, McClure-Begley T, Whiteaker P, Grady SR, Salminen O, Gardner PD, Lester HA, Tapper AR (2010) Dopamine D2-receptor activation elicits akinesia, rigidity, catalepsy, and tremor in mice expressing hypersensitive {alpha}4 nicotinic receptors via a cholinergic-dependent mechanism. The FASEB Journal 24: 49–57. https://doi.org/10.1096/fj.09-137034
- Zheleva-Dimitrova D, Simeonova R, Kondeva-Burdina M, Savov Y, Balabanova V, Zengin G, Petrova A, Gevrenova R (2023) Antioxidant and hepatoprotective potential of Echinops ritro L. Extracts on induced oxidative stress in vitro/in vivo. International Journal of Molecular Sciences 24(12): 9999. https://doi.org/10.3390/ijms24129999
- Zitouni-Nourine SH, Belyagoubi-Benhammou N, El-Houaria Zitouni-Haouar F, Douahi O, Chenafi F, Fetati H, Chabane Sari S, Benmahieddine A, Zaoui C, Mekaouche FZN, Atik Bekkara F, Kambouche N, Gismondi A, Toumi H (2022) Echinops spinosissimus turra root methanolic extract: characterization of the bioactive components and relative wound healing, antimicrobial and antioxidant properties. Plants 11: 3440. https://doi.org/10.3390/plants11243440