Effect of solid herbal extract of Primula veris L. on the psychoemotional state of rats after chronic alcohol intoxication
Authors
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Margarita V. Kustova
Volgograd State Medical University
https://orcid.org/0000-0002-6287-4120
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Elena A. Muzyko
Volgograd State Medical University, Volgograd, Russia
https://orcid.org/0000-0003-0535-9787
- Yakov V. Tivon City Clinical Emergency Hospital No. 25, Volgograd, Russia
-
Valentina N. Perfilova
Volgograd State Medical University
https://orcid.org/0000-0002-2457-8486
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Valery A. Kataev
Bashkir State Medical University, Ufa, Russia
https://orcid.org/0000-0001-9300-0015
-
Guzel M. Latypova
Bashkir State Medical University, Ufa, Russia
https://orcid.org/0000-0001-5178-5379
-
Ivan N. Tyurenkov
Volgograd State Medical University, Volgograd, Russia
https://orcid.org/0000-0001-7574-3923
-
Victor S. Sirotenko
Volgograd State Medical University, Volgograd, Russia
https://orcid.org/0000-0003-2249-020X
DOI:
https://doi.org/10.18413/rrpharmacology.12.1101Abstract
Introduction: The aim of the study was the effect of solid herbal extract of Primula veris L. and comparison drugs phenotropil and mildronate on the psycho-emotional state of rats after chronic alcohol intoxication (CAI).
Materials and Methods: CAI was modeled by replacing drinking water with a 10% solution of ethyl alcohol with sucrose (50 g/L) for 6 months. After alcoholization, rats at the age of 16 months were divided into the following groups: 1 – intact – animals without CAI received oral 0.9% sodium chloride solution for 14 days; 2 – control – rats after ethanol withdrawal, which were injected with a 0.9% sodium chloride solution in a similar regimen; 3, 4 and 5 – experimental – females after CAI received oral solid herbal extract of Primula veris L. at a dose of 30 mg/kg, phenotropil 25 mg/kg, mildronate 50 mg/kg, respectively. After the end of treatment, to assess the psycho-emotional state of the animals, the Open field test, Elevated plus maze test, Marble burying test and Porsolt forced swim test were performed.
Results and Discussion: In animals after CAI, increased anxiety is observed, which manifested itself in a greater number of stands with support, urinations and boluses in the Open field test compared to the intact group. In the Elevated plus maze test, the trend remained the same: rats in the control group entered the open compartment installation less often, hung from it less often, and spent less time in the open compartment. In addition, females after CAI exhibited compulsive behavior in the Marble burying test. In the Porsolt forced swim test, animals in the control group had a shorter period of active swimming compared to intact females and a longer period of immobilization, which indicates depressive behavior in the former. Solid herbal extract of Primula veris L., phenotropil and mildronate contributed to the improvement of the psycho-emotional state of animals after CAI.
Conclusion: Thus, solid herbal extract of Primula veris L. at a dose of 30 mg/kg, which was administered orally once a day to female rats for 14 days after the withdrawal of ethanol, has a pronounced anxiolytic and antidepressant effect, while phenotropil and mildronate (25 mg/kg and 50 mg/kg, respectively, in a similar regimen) had a greater anticompulsive effect.
Graphical Abstract
Keywords:
chronic alcohol intoxication, anxiety, compulsive and depressive behavior, solid herbal extract of Primula veris L.References
Anker JJ, Kummerfeld E, Rix A, Burwell SJ, Kushner MG (2019) Causal network modeling of the determinants of drinking behavior in comorbid alcohol use and anxiety disorder. Alcoholism, Clinical and Experimental Research 43(1): 91–97. https://doi.org/10.1111/acer.13914 [PubMed] [PMC]
Baratov KRU, Mahmudov LU, Matchanov UD, Tagajalieva NA (2020) Characterisation of the anti-inflammatory and antioxidant effects of the supramolecular complex of rutin. Universum: Chemistry and Biology 74(8): 15–18. [in Russian]
Bychenkova MA, Tyurenkov IN, Mokrousov IS, Perfilova VN, Latypova GM, Kataev VA (2018) Influence of primula veris dense extract on endothelial dysfunction under conditions of experimental arterial hypertension. Experimental and Clinical Pharmacology [Eksperimental’naya i Klinicheskaya Farmakologiya] 81(9): 6–12. https://doi.org/10.30906/0869-2092-2018-81-9-6-12 [in Russian]
Ding C, O’Neill D, Bell, S, Stamatakis E, Britton A (2021) Association of alcohol consumption with morbidity and mortality in patients with cardiovascular disease: original data and meta-analysis of 48,423 men and women. BMC Medicine 19(1): 167. https://doi.org/10.1186/s12916-021-02040-2 [PubMed] [PMC]
Fedin AI, Soloveva EY, Baranova OA (2020) Evaluation of effects of stepwise and oral Mildronate therapy on neurological status, cognitive functions, and asthenic syndrome in patients with cardiovascular comorbidities. Nervous Diseases 3: 15–24. https://doi.org/10.24411/2226-0757-2020-12225 [in Russian]
Gushcha VK, Lelevich SV, Shejbak VM (2019) Neurotransmitter disturbances in some parts of the rat brain and their correction under chronic and intermittent alcohol intoxication. Biomedical Chemistry [Biomeditsinskaya Khimiya] 65(1): 21–27. https://doi.org/10.18097/PBMC20196501021 [PubMed] [in Russian]
Hammoud N, Jimenez-Shahed J (2019) Chronic neurologic effects of alcohol. Clinics in Liver Disease 23(1): 141–155. https://doi.org/10.1016/j.cld.2018.09.010 [PubMed]
Ageeva LI, Alexandrova GA, Golubev NA, Kirillova GN, Ogryzko EV, Oskov YuI, Nam PD, Kharkov TL, Chumarina VZh (2021) Healthcare in Russia. Statistical Digest. Moscow. Rosstat, 171 pp.
Kamal H, Tan GC, Ibrahim SF, Shaikh MF, Mohamed IN, Mohamed RMP, Hamid AA, Ugusman A, Kumar J (2020) Alcohol use disorder, neurodegeneration, Alzheimer’s and Parkinson’s disease: Interplay between oxidative stress, neuroimmune response and excitotoxicity. Frontiers in Cellular Neuroscience 14: 282. https://doi.org/10.3389/fncel.2020.00282 [PubMed] [PMC]
Kataev V, Perfilova VN, Prokofiev II, Nesterova AA, Isaeva JK, Kustova MV, Tyurenkov IN, Brel AK, Kataev VA (2025) Cardioprotective effect of hydroxybenzoic acid ester containing neuroactive acid, compound F-26, in conditions of isoproterenol heart failure in rats. Research Results in Pharmacology11(4): 222–234. https://doi.org/10.18413/rrpharmacology.11.811
Kryzhanovskij SA, Corin IB, Kolik LG, Stolyaruk VN, Vititnova MB, Ionova EO, Sorokina AV, Durnev AD, Seredenin SB (2015) Translational model of alcoholic cardiomyopathy. Molecular Medicine 3: 40–47.
Liu M, Guo S, Huang D, Hu D, Wu Y, Zhou W, Song W (2022) Chronic alcohol exposure alters gene expression and neurodegeneration pathways in the brain of adult mice. Journal of Alzheimer’s Disease 86(1): 315–331. https://doi.org/10.3233/JAD-215508 [PubMed]
Patel RR, Wolfe SA, Borgonetti V, Gandhi PJ, Rodriguez L, Snyder AE, D'Ambrosio S, Bajo M, Domissy A, Head S, Contet C, Dayne Mayfield R, Roberts AJ, Roberto M (2022) Ethanol withdrawal-induced adaptations in prefrontal corticotropin releasing factor receptor 1-expressing neurons regulate anxiety and conditioned rewarding effects of ethanol. Molecular Psychiatry 27(8): 3441–3451. https://doi.org/10.1038/s41380-022-01642-3 [PubMed] [PMC]
Popova TA, Muzyko EA, Kustova MV, Bychenkova MA, Perfilova VN, Prokof'ev II, Samojlova MA, Tyurenkov IN, Latypova GM, Kataev VA (2018) Influence of the dense extract from herb of primula veris l. on the oxidative stress development and the functional state of the cardiomyocytes mitochondria of rats with experimental chronic heart failure. Biomedical Chemistry [Biomeditsinskaya Khimiya] 64(4): 334–343. https://doi.org/10.18097/PBMC20186404334 [PubMed] [in Russian]
Popova TA, Kustova MV, Khusainova GK, Perfilova VN, Prokofiev II, Smolnyakova YA, Borodkina LE, Tyurenkov IN, Ostrovskiy OV, Vasil’eva OS (2021) Changes in the respiratory function of the heart and brain mitochondria of animals after chronic alcohol intoxication affected by a new GABA derivative. Research Results in Pharmacology 7(1): 33–40. https://doi.org/10.3897/rrpharmacology.7.60469
Potupchik TV, Veselova OF, Gackih IV (2019) Pharmacotherapeutic aspects of nootropics use in people with alcohol dependence. Medical Alphabet 2(19): 37–41. https://doi.org/10.33667/2078-5631-2019-2-19(394)-37-41 [in Russian]
Sapkota P, Mattoo SK, Mahintamani T, Ghosh A (2022) Depressive symptoms in early alcohol or opioid abstinence: course & correlates. Journal of Addictive Diseases 40(1): 35–46. https://doi.org/10.1080/10550887.2021.1925617 [PubMed]
Savage LM, Nunes PT, Gursky ZH, Milbocker KA, Klintsova AY (2021) Midline thalamic damage associated with alcohol-use disorders: Disruption of distinct thalamocortical pathways and function. Neuropsychology Review 31(3): 447–471. https://doi.org/10.1007/s11065-020-09450-8
Siddiqi MT, Podder D, Pahng AR, Athanason AC, Nadav T, Cates-Gatto C, Kreifeldt M, Contet C, Roberts AJ, Edwards S, Roberto M, Varodayan FP (2023) Prefrontal cortex glutamatergic adaptations in a mouse model of alcohol use disorder. Addiction Neuroscience 9: 100137. https://doi.org/10.1016/j.addicn.2023.100137[PubMed] [PMC]
Smirnova LA, Suchkov EA, Kuznecov KA, Ryabuha AF, Perfilova VN, Popova TA, Tyurenkov IN, Bychenkova MA, Latypova GM, Kataev VA (2020) Quantitative determination of rutin in biological samples of rats upon administration of primula veris L. herbal dense extract. Pharmaceutical Chemictry Journal [Khimiko-Farmatsevticheskii Zhurnal] 54(12): 25–28. https://doi.org/10.30906/0023-1134-2020-54-12-25-28 [in Russian]
Sushma, Mishra S, Kanchan S, Divakar A, Jha G, Sharma D, Kapoor R, Kumar Rath S (2023) Alcohol induces ER stress and apoptosis by inducing oxidative stress and disruption of calcium homeostasis in glial cells. Food and Chemical Toxicology 182: 114192. https://doi.org/10.1016/j.fct.2023.114192 [PubMed]
Wang G, Li DY, Vance DE, Li W (2023) Alcohol use disorder as a risk factor for cognitive impairment. Journal of Alzheimer’s Disease 94(3): 899–907. https://doi.org/10.3233/JAD-230181 [PubMed]
Wei H, Yu C, Zhang C, Ren Y, Guo L, Wang T, Chen F, Li Y, Zhang X, Wang H, Liu J (2023) Butyrate ameliorates chronic alcoholic central nervous damage by suppressing microglia-mediated neuroinflammation and modulating the microbiome-gut-brain axis. Biomédecine & Pharmacothérapie 160: 114308. https://doi.org/10.1016/j.biopha.2023.114308 [PubMed]
WHO: Harmful use of alcohol kills more than 3 million people each year, most of them men https://www.who.int/ru/news/item/21-09-2018-harmful-use-of-alcohol-kills-more-than-3-million-people-each-year--most-of-them-men
Wiers CE, Cunningham SI, Tomasi DG, Ernst T, Chang L, Shokri-Kojori E, Wang GJ, Volkow ND (2020) Elevated thalamic glutamate levels and reduced water diffusivity in alcohol use disorder: Association with impulsivity. Psychiatry Research: Neuroimaging 305: 111185. https://doi.org/10.1016/j.pscychresns.2020.111185[PubMed] [PMC]
Wołyńczyk-Gmaj D, Jakubczyk A, Trucco EM, Kobyliński P, Zaorska J, Gmaj B, Kopera M (2022) Emotional dysregulation, anxiety symptoms and insomnia in individuals with alcohol use disorder. International Journal of Environmental Research and Public Health 19(5): 2700. https://doi.org/10.3390/ijerph19052700 [PubMed] [PMC]
Yao H, Zhang D, Yu H, Shen H, Lan X, Liu H, Chen X, Wu X, Zhang G, Wang X (2022) Chronic ethanol exposure induced anxiety‐like behaviour by altering gut microbiota and GABA system. Addiction Biology 27(5): e13203. https://doi.org/10.1111/adb.13203 [PubMed]
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Copyright (c) 2026 Kustova MV, Muzyko EA, Tivon YaV, Perfilova VN, Kataev VA, Latypova GM, Tyurenkov IN, Sirotenko VS
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