Trihexyphenidyl Alters Its Host’s Metabolism, Neurobehavioral Patterns, and Gut Microbiome Feedback Loop—The Modulating Role of Anacyclus pyrethrum
Abstract
:1. Introduction
2. Material and Methods
2.1. Animals
- (1)
- The control group received a vehicle (saline solution 0.9%).
- (2)
- The THP-dependent group underwent 30 days of daily THP administration (from day 4 to day 33 of the experiment), followed by a 7-day withdrawal phase (from day 34 to day 40).
- (3)
- The THP + post-AEAP group included rats treated with a daily THP administration for 30 days (from day 4 to day 33 of the experiment), and post-treated with AEAP (200 mg/kg) for 7 days (from day 34 to day 40), to assess the potential curative effects of AEAP.
- (4)
- The THP + co-AEAP group involved rats administered AEAP (200 mg/kg) 30 min prior to THP administration for 30 days (from day 4 to day 33), followed by a 7-day withdrawal phase (from day 34 to day 40), to explore the potential preventive effects of AEAP (Figure S1).
2.2. Drugs Administration
2.3. Plant Material and Preparation of the Aqueous Extract of A. pyrethrum
2.4. Conditioned Place Preference (CPP)
2.5. Behavioral Assessment
2.5.1. Open Field Test (OFT)
2.5.2. Porsolt’s Forced Swim Test (FST)
2.5.3. Elevated plus Maze (EPM)
2.6. Biochemical Analyses
2.7. Oxidative Stress
2.7.1. LPO Assay
2.7.2. Catalase (CAT) Activity
2.7.3. Superoxide Dismutase (SOD) Activity
2.8. Gut Microbiota Determination
2.8.1. MALDI-TOF MS Spectra for Mass Spectral Profiles
2.8.2. MALDI-TOF MS Data Acquisition and Processing
2.9. Histological Study
2.10. Statistical Analyses
3. Results
3.1. Trihexyphenidyl-Induced CPP
3.2. Trihexyphenidyl Withdrawal-Induced Anxiety and Depression, and the Potential of AEAP to Alleviate Adverse Outcomes
3.3. Trihexyphenidyl Withdrawal-Induced Cortisol Levels Elevation
3.4. Trihexyphenidyl Withdrawal-Induced Oxidative Stress, and the Antioxidant Capacity of AEAP
3.5. Alterations in Microbiota Density and Composition during Trihexyphenidyl Withdrawal, and the Ameliorative Effect of AEAP
3.6. Alterations in Intestinal Tissue during Trihexyphenidyl Withdrawal, and the Ameliorative Effect of AEAP
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Jilani, T.N.; Sabir, S.; Sharma, S. Trihexyphenidyl. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2023. Available online: http://www.ncbi.nlm.nih.gov/books/NBK519488/ (accessed on 1 June 2023).
- Bergman, H.; Soares-Weiser, K. Anticholinergic medication for antipsychotic-induced tardive dyskinesia. Cochrane Database Syst. Rev. 2018, 1, CD000204. [Google Scholar] [CrossRef] [PubMed]
- Volgin, A.D.; Yakovlev, O.A.; Demin, K.A.; Alekseeva, P.A.; Kyzar, E.J.; Collins, C.; Nichols, D.E.; Kalueff, A.V. Understanding Central Nervous System Effects of Deliriant Hallucinogenic Drugs through Experimental Animal Models. ACS Chem. Neurosci. 2019, 10, 143–154. [Google Scholar] [CrossRef] [PubMed]
- Naja, W.J.; Halaby, A. Anticholinergic Use and Misuse in Psychiatry: A Comprehensive and Critical Review. J. Alcohol. Drug Depend. 2017, 5, 263. [Google Scholar] [CrossRef]
- Olanrewaju, R.S.; Mannir, A.; Olanrewaju, R.S.; Mannir, A. Trihexyphenidyl abuse in psychiatric outpatient clinic of a general hospital in Northern Nigeria. J. Addict. Med. Ther. Sci. 2020, 6, 003–008. [Google Scholar]
- Chiappini, S.; Mosca, A.; Miuli, A.; Semeraro, F.M.; Mancusi, G.; Santovito, M.C.; Di Carlo, F.; Pettorruso, M.; Guirguis, A.; Corkery, J.M.; et al. Misuse of Anticholinergic Medications: A Systematic Review. Biomedicines 2022, 10, 355. [Google Scholar] [CrossRef] [PubMed]
- Downs, A.M.; Fan, X.; Donsante, C.; Jinnah, H.A.; Hess, E.J. Trihexyphenidyl rescues the deficit in dopamine neurotransmission in a mouse model of DYT1 dystonia. Neurobiol. Dis. 2019, 125, 115–122. [Google Scholar] [CrossRef] [PubMed]
- Mahal, P.; Nishanth, K.N.; Mahapatra, A.; Sarkar, S.; Balhara, Y.P.S. Trihexyphenidyl Misuse in Delusional Disorder. J. Neurosci. Rural. Pract. 2018, 9, 428–430. [Google Scholar] [CrossRef]
- Migirov, A.; Datta, A.R. Physiology, Anticholinergic Reaction. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2023. Available online: http://www.ncbi.nlm.nih.gov/books/NBK546589/ (accessed on 24 July 2023).
- Xiao, H.W.; Ge, C.; Feng, G.X.; Li, Y.; Luo, D.; Dong, J.L.; Li, H.; Wang, H.; Cui, M.; Fan, S.J. Gut microbiota modulates alcohol withdrawal-induced anxiety in mice. Toxicol. Lett. 2018, 287, 23–30. [Google Scholar] [CrossRef]
- Chen, Y.; Xu, J.; Chen, Y. Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders. Nutrients 2021, 13, 2099. [Google Scholar] [CrossRef]
- Grochowska, M.; Wojnar, M.; Radkowski, M. The gut microbiota in neuropsychiatric disorders. Acta Neurobiol. Exp. 2018, 78, 69–81. [Google Scholar] [CrossRef]
- Zhang, Y.; Zhang, J.; Wu, J.; Zhu, Q.; Chen, C.; Li, Y. Implications of gut microbiota dysbiosis and fecal metabolite changes in psychologically stressed mice. Front. Microbiol. 2023, 14, 1124454. [Google Scholar] [CrossRef] [PubMed]
- Ni, Q.; Zhang, P.; Li, Q.; Han, Z. Oxidative Stress and Gut Microbiome in Inflammatory Skin Diseases. Front. Cell Dev. Biol. 2022, 10, 849985. [Google Scholar] [CrossRef] [PubMed]
- Tse, J.K. Gut microbiota, nitric oxide, and microglia as prerequisites for neurodegenerative disorders. ACS Chem. Neurosci. 2017, 8, 1438–1447. [Google Scholar] [CrossRef] [PubMed]
- Kunst, C.; Schmid, S.; Michalski, M.; Tümen, D.; Buttenschön, J.; Müller, M.; Gülow, K. The Influence of Gut Microbiota on Oxidative Stress and the Immune System. Biomedicines 2023, 11, 1388. [Google Scholar] [CrossRef] [PubMed]
- Dumitrescu, L.; Popescu-Olaru, I.; Cozma, L.; Tulbă, D.; Hinescu, M.E.; Ceafalan, L.C.; Gherghiceanu, M.; Popescu, B.O. Oxidative Stress and the Microbiota-Gut-Brain Axis. Oxid. Med. Cell Longev. 2018, 2018, 2406594. [Google Scholar] [CrossRef]
- Atanasov, A.G.; Zotchev, S.B.; Dirsch, V.M.; Supuran, C.T. Natural products in drug discovery: Advances and opportunities. Nat. Rev. Drug Discov. 2021, 20, 200–216. [Google Scholar] [CrossRef]
- Zougagh, S.; Belghiti, A.; Rochd, T.; Zerdani, I.; Mouslim, J. Medicinal and Aromatic Plants Used in Traditional Treatment of the Oral Pathology: The Ethnobotanical Survey in the Economic Capital Casablanca, Morocco (North Africa). Nat. Prod. Bioprospect. 2018, 9, 35–48. [Google Scholar] [CrossRef]
- Lee, E.L.; Barnes, J. Prevalence of Use of Herbal and Traditional Medicines. In Pharmacovigilance for Herbal and Traditional Medicines: Advances, Challenges and International Perspectives; Barnes, J., Ed.; Springer International Publishing: Cham, Switzerland, 2022; pp. 15–25. [Google Scholar] [CrossRef]
- Bezza, K.; Gabbas, Z.E.; Laadraoui, J.; Laaradia, M.A.; Oufquir, S.; Chait, A. Ameliorative potential of Anacyclus pyrethrum extract in generalized seizures in rat: Possible cholinergic mediated mechanism. Bangladesh J. Pharmacol. 2019, 14, 188–195. [Google Scholar] [CrossRef]
- Baslam, A.; Aitbaba, A.; Aboufatima, R.; Agouram, F.; Boussaa, S.; Chait, A.; Baslam, M. Phytochemistry, Antioxidant Potential, and Antibacterial Activities of Anacyclus pyrethrum: Promising Bioactive Compounds. Horticulturae 2023, 9, 1196. [Google Scholar] [CrossRef]
- Baslam, A.; Aitbaba, A.; Lamrani Hanchi, A.; Tazart, Z.; Aboufatima, R.; Soraa, N.; Ait-El-Mokhtar, M.; Boussaa, S.; Baslam, M.; Chait, A. Modulation of Gut Microbiome in Ecstasy/MDMA-Induced Behavioral and Biochemical Impairment in Rats and Potential of Post-Treatment with Anacyclus pyrethrum L. Aqueous Extract to Mitigate Adverse Effects. Int. J. Mol. Sci. 2023, 24, 9086. [Google Scholar] [CrossRef]
- Bezza, K.; Laadraoui, J.; Gabbas, Z.E.; Laaradia, M.A.; Oufquir, S.; Aboufatima, R.; Gharrassi, I.; Chait, A. Effects of Anacyclus pyrethrum on affective behaviors and memory during withdrawal from cigarette smoke exposure in rats. Pharmacogn. Mag. 2020, 16, 123. [Google Scholar] [CrossRef]
- Seaman, R.W., Jr.; Collins, G.T. Impact of Morphine Dependence and Withdrawal on the Reinforcing Effectiveness of Fentanyl, Cocaine, and Methamphetamine in Rats. Front. Pharmacol. 2021, 12, 691700. [Google Scholar] [CrossRef] [PubMed]
- Barbosa Méndez, S.; Salazar-Juárez, A. Mirtazapine attenuates anxiety- and depression-like behaviors in rats during cocaine withdrawal. J. Psychopharmacol. 2019, 33, 589–605. [Google Scholar] [CrossRef] [PubMed]
- Yankelevitch-Yahav, R.; Franko, M.; Huly, A.; Doron, R. The Forced Swim Test as a Model of Depressive-like Behavior. J. Vis. Exp. JoVE 2015, 52587. [Google Scholar]
- Schneider, P.; Ho, Y.J.; Spanagel, R.; Pawlak, C. A Novel Elevated Plus-Maze Procedure to Avoid the One-Trial Tolerance Problem. Front. Behav. Neurosci. 2011, 5, 43. [Google Scholar] [CrossRef] [PubMed]
- Katerji, M.; Filippova, M.; Duerksen-Hughes, P. Approaches and Methods to Measure Oxidative Stress in Clinical Samples: Research Applications in the Cancer Field. Oxid. Med. Cell Longev. 2019, 2019, 1279250. [Google Scholar] [CrossRef]
- Esterbauer, H. Cytotoxicity and genotoxicity of lipid-oxidation products. Am. J. Clin. Nutr. 1993, 57, 779S–786S. [Google Scholar] [CrossRef]
- Pomierny-Chamioło, L.; Moniczewski, A.; Wydra, K.; Suder, A.; Filip, M. Oxidative Stress Biomarkers in Some Rat Brain Structures and Peripheral Organs Underwent Cocaine. Neurotox. Res. 2013, 23, 92–102. [Google Scholar] [CrossRef]
- Aebi, H. [13] Catalase in vitro. Methods Enzymol. 1984, 105, 121–126. [Google Scholar]
- Beauchamp, C.; Fridovich, I. Superoxide dismutase: Improved assays and an assay applicable to acrylamide gels. Anal. Biochem. 1971, 44, 276–287. [Google Scholar] [CrossRef]
- Malatesta, M. Histological and Histochemical Methods—Theory and Practice. Eur. J. Histochem. EJH 2016, 60, 2639. [Google Scholar] [CrossRef]
- Guirguis, A. Misuse of prescription and over-the-counter drugs to obtain illicit highs: How pharmacists can prevent abuse. Pharm. J. 2020, 305, 7943. [Google Scholar] [CrossRef]
- Broderick, E.D.; Metheny, H.; Crosby, B. Anticholinergic Toxicity. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2023. Available online: http://www.ncbi.nlm.nih.gov/books/NBK534798/ (accessed on 30 October 2023).
- Diagne, I.; Petit, V.; Boiro, D. Accidental Trihexyphenidyl Intoxication in a Seven-Year-Old Child: A Case Report from Senegal. J. Psychiatry Ment. Disord. 2021, 6, 1045. [Google Scholar]
- Langman, L.J.; Jannetto, P.J. Toxicology and the clinical laboratory. In Contemporary Practice in Clinical Chemistry; Elsevier: Amsterdam, The Netherlands, 2020; pp. 917–951. Available online: https://www.sciencedirect.com/science/article/pii/B9780128154991000521 (accessed on 30 October 2023).
- McAnena, L.; Plant, G.T.; Wong, S.H. Anticholinergic syndrome: Blurred vision and headache. Pract. Neurol. 2023, 23, 339–342. [Google Scholar] [CrossRef]
- Martinotti, G.; Risio, L.D.; Vannini, C.; Schifano, F.; Pettorruso, M.; Giannantonio, M.D. Substance-related exogenous psychosis: A postmodern syndrome. CNS Spectr. 2021, 26, 84–91. [Google Scholar] [CrossRef]
- Naji, A.; Gatling, J.W. Muscarinic Antagonists. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2023. Available online: http://www.ncbi.nlm.nih.gov/books/NBK557541/ (accessed on 30 October 2023).
- Popkin, B.M.; D’Anci, K.E.; Rosenberg, I.H. Water, Hydration and Health. Nutr. Rev. 2010, 68, 439–458. [Google Scholar] [CrossRef]
- Maltese, M.; Martella, G.; Madeo, G.; Fagiolo, I.; Tassone, A.; Ponterio, G.; Sciamanna, G.; Burbaud, P.; Conn, P.J.; Bonsi, P.; et al. Anticholinergic drugs rescue synaptic plasticity in DYT1 dystonia: Role of M1 muscarinic receptors. Mov. Disord. Off. J. Mov. Disord. Soc. 2014, 29, 1655–1665. [Google Scholar] [CrossRef]
- Brown, M.T.C.; Tan, K.R.; O’Connor, E.C.; Nikonenko, I.; Muller, D.; Lüscher, C. Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning. Nature 2012, 492, 452–456. [Google Scholar] [CrossRef] [PubMed]
- Chehovich, C.; Lee, C.; Demler, T.L. Irreversible Effects of Anticholinergic Withdrawal in the Elderly: A Case Report. Chehovich. Aging Pathobiology and Therapeutics. 2021. Available online: http://antpublisher.com/index.php/APT/article/view/383 (accessed on 30 October 2023).
- Lupu, A.M.; MacCamy, K.L.; Gannon, J.M.; Brar, J.S.; Chengappa, K.R. Less is more: Deprescribing anticholinergic medications in persons with severe mental illness. Ann. Clin. Psychiatry 2021, 33, 80–92. [Google Scholar] [CrossRef]
- Threlfell, S.; Clements, M.A.; Khodai, T.; Pienaar, I.S.; Exley, R.; Wess, J.; Cragg, S.J. Striatal Muscarinic Receptors Promote Activity Dependence of Dopamine Transmission via Distinct Receptor Subtypes on Cholinergic Interneurons in Ventral versus Dorsal Striatum. J. Neurosci. 2010, 30, 3398–3408. [Google Scholar] [CrossRef]
- Ahmad, M.P.; Arshad, H.; Kalam, N.A.; Anshu, M.; Hasin, A.M.; Shadma, W. Effect of the aqueous extract of Mentha arvensis on haloperidol induced catalepsy in albino mice. J. Clin. Diagn. Res. 2012, 6, 542–546. [Google Scholar]
- Shivakumar, B.R.; Ravindranath, V. Oxidative stress induced by administration of the neuroleptic drug haloperidol is attenuated by higher doses of haloperidol. Brain Res. 1992, 595, 256–262. [Google Scholar] [CrossRef] [PubMed]
- Vona, R.; Pallotta, L.; Cappelletti, M.; Severi, C.; Matarrese, P. The Impact of Oxidative Stress in Human Pathology: Focus on Gastrointestinal Disorders. Antioxidants 2021, 10, 201. [Google Scholar] [CrossRef] [PubMed]
- Wong, K.K.L.; Tang, L.C.Y.; Zhou, J.; Ho, V. Analysis of spatiotemporal pattern and quantification of gastrointestinal slow waves caused by anticholinergic drugs. Organogenesis 2017, 13, 39–62. [Google Scholar] [CrossRef] [PubMed]
- Sulegaon, R.; Shete, S.; Kulkarni, D. Histological Spectrum of Large Intestinal Lesions with Clinicopathological Correlation. J. Clin. Diagn. Res. 2015, 9, EC30–EC34. [Google Scholar] [CrossRef] [PubMed]
- Yu, Z.; Hao, L.; Li, Z.; Sun, J.; Chen, H.; Huo, H.; Li, X.; Shan, Z.; Li, H. Correlation between slow transit constipation and spleen Qi deficiency, and gut microbiota: A pilot study. J. Tradit. Chin. Med. 2022, 42, 353. [Google Scholar]
- He, L.; He, T.; Farrar, S.; Ji, L.; Liu, T.; Ma, X. Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species. Cell. Physiol. Biochem. 2017, 44, 532–553. [Google Scholar] [CrossRef]
- Pahuja, M.; Mehla, J.; Reeta, K.H.; Joshi, S.; Gupta, Y.K. Root extract of Anacyclus pyrethrum ameliorates seizures, seizure-induced oxi-dative stress and cognitive impairment in experimental animals. Epilepsy Res. 2012, 98, 157–165. [Google Scholar] [CrossRef]
- Sri Indu, N. Evaluation of Anti-Parkinsonian Effect of Anacyclus pyrethrum Linn Root in MPTP Induced Neurodegeneration. Master’s Thesis, Annai J.K.K. Sampoorani Ammal College of Pharmacy, Komarapalayam, India, 2021. Available online: http://repository-tnmgrmu.ac.in/20785/ (accessed on 30 October 2023).
- Sujith, K.; Darwin, C.R.; Sathish Suba, V. Memory-enhancing activity of Anacyclus pyrethrum in albino Wistar rats. Asian Pac. J. Trop. Dis. 2012, 2, 307–311. [Google Scholar] [CrossRef]
- Singh, P.; Singh, D.; Goel, R.K. Phytoflavonoids: Antiepileptics for the future. Int. J. Pharm. Pharm. Sci. 2014, 6, 51–66. [Google Scholar]
- Zaidi, S.M.A.; Pathan, S.A.; Singh, S.; Jamil, S.; Ahmad, F.J.; Khar, R.K. Anticonvulsant, Anxiolytic and Neurotoxicity Profile of Aqarqarha (Anacyclus pyrethrum) DC (Compositae) Root Ethanolic Extract. Pharmacol. Pharm. 2013, 4, 535. [Google Scholar] [CrossRef]
- Bonaz, B.; Bazin, T.; Pellissier, S. The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis. Front. Neurosci. 2018, 12, 49. [Google Scholar] [CrossRef] [PubMed]
- Herlihy, B.; Roy, S. Gut-Microbiome Implications in Opioid Use Disorder and Related Behaviors. Adv. Drug Alcohol. Res. 2022, 2, 10311. [Google Scholar] [CrossRef]
- Sarkar, A.; Lehto, S.M.; Harty, S.; Dinan, T.G.; Cryan, J.F.; Burnet, P.W.J. Psychobiotics and the Manipulation of Bacteria–Gut–Brain Signals. Trends Neurosci. 2016, 39, 763–781. [Google Scholar] [CrossRef] [PubMed]
- Simpson, S.; Mclellan, R.; Wellmeyer, E.; Matalon, F.; George, O. Drugs and Bugs: The Gut-Brain Axis and Substance Use Disorders. J. Neuroimmune Pharmacol. 2022, 17, 33–61. [Google Scholar] [CrossRef] [PubMed]
- Divyashri, G.; Krishna, G.; Muralidhara; Prapulla, S.G. Probiotic attributes, antioxidant, anti-inflammatory and neuromodulatory effects of Enterococcus faecium CFR 3003: In vitro and in vivo evidence. J. Med. Microbiol. 2015, 64, 1527–1540. [Google Scholar] [CrossRef] [PubMed]
- Cheon, M.J.; Lim, S.M.; Lee, N.K.; Paik, H.D. Probiotic Properties and Neuroprotective Effects of Lactobacillus buchneri KU200793 Isolated from Korean Fermented Foods. Int. J. Mol. Sci. 2020, 21, 1227. [Google Scholar] [CrossRef]
- Sirin, S.; Aslim, B. Characterization of lactic acid bacteria derived exopolysaccharides for use as a defined neuroprotective agent against amyloid beta1–42-induced apoptosis in SH-SY5Y cells. Sci. Rep. 2020, 10, 8124. [Google Scholar] [CrossRef]
- Shandilya, S.; Kumar, S.; Kumar Jha, N.; Kumar Kesari, K.; Ruokolainen, J. Interplay of gut microbiota and oxidative stress: Perspective on neurodegeneration and neuroprotection. J. Adv. Res. 2022, 38, 223–244. [Google Scholar] [CrossRef]
- Bonfili, L.; Cecarini, V.; Cuccioloni, M.; Angeletti, M.; Berardi, S.; Scarpona, S.; Rossi, G.; Eleuteri, A.M. SLAB51 Probiotic Formulation Activates SIRT1 Pathway Promoting Antioxidant and Neuroprotective Effects in an AD Mouse Model. Mol. Neurobiol. 2018, 55, 7987–8000. [Google Scholar] [CrossRef]
- Patterson, E.; Ryan, P.M.; Wiley, N.; Carafa, I.; Sherwin, E.; Moloney, G.; Franciosi, E.; Mandal, R.; Wishart, D.S.; Tuohy, K.; et al. Gamma-aminobutyric acid-producing lactobacilli positively affect metabolism and depressive-like behaviour in a mouse model of metabolic syndrome. Sci. Rep. 2019, 9, 16323. [Google Scholar] [CrossRef] [PubMed]
- Yunes, R.A.; Poluektova, E.U.; Dyachkova, M.S.; Klimina, K.M.; Kovtun, A.S.; Averina, O.V.; Orlova, V.S.; Danilenko, V.N. GABA production and structure of gadB/gadC genes in Lactobacillus and Bifidobacterium strains from human microbiota. Anaerobe 2016, 42, 197–204. [Google Scholar] [CrossRef] [PubMed]
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Baslam, A.; Azraida, H.; Aboufatima, R.; Ait-El-Mokhtar, M.; Dilagui, I.; Boussaa, S.; Chait, A.; Baslam, M. Trihexyphenidyl Alters Its Host’s Metabolism, Neurobehavioral Patterns, and Gut Microbiome Feedback Loop—The Modulating Role of Anacyclus pyrethrum. Antioxidants 2024, 13, 26. https://doi.org/10.3390/antiox13010026
Baslam A, Azraida H, Aboufatima R, Ait-El-Mokhtar M, Dilagui I, Boussaa S, Chait A, Baslam M. Trihexyphenidyl Alters Its Host’s Metabolism, Neurobehavioral Patterns, and Gut Microbiome Feedback Loop—The Modulating Role of Anacyclus pyrethrum. Antioxidants. 2024; 13(1):26. https://doi.org/10.3390/antiox13010026
Chicago/Turabian StyleBaslam, Abdelmounaim, Hajar Azraida, Rachida Aboufatima, Mohamed Ait-El-Mokhtar, Ilham Dilagui, Samia Boussaa, Abderrahman Chait, and Marouane Baslam. 2024. "Trihexyphenidyl Alters Its Host’s Metabolism, Neurobehavioral Patterns, and Gut Microbiome Feedback Loop—The Modulating Role of Anacyclus pyrethrum" Antioxidants 13, no. 1: 26. https://doi.org/10.3390/antiox13010026
APA StyleBaslam, A., Azraida, H., Aboufatima, R., Ait-El-Mokhtar, M., Dilagui, I., Boussaa, S., Chait, A., & Baslam, M. (2024). Trihexyphenidyl Alters Its Host’s Metabolism, Neurobehavioral Patterns, and Gut Microbiome Feedback Loop—The Modulating Role of Anacyclus pyrethrum. Antioxidants, 13(1), 26. https://doi.org/10.3390/antiox13010026