Improvement of antioxidant protection and energy production in neurodegenerative processes in the brain caused by long-term alcoholism under the influence of Lophantus chinensis Benth extract

Long-term alcohol abuse causes psycho-emotional and cognitive impairment, including severe dementia. Oxidative stress is considered one of the main mechanisms in the cognitive disorders pathophysiology caused by long-term alcoholism. In this regard, the search for substances capable of correcting mitochondrial dysfunction and oxidative stress that arise as a result of prolonged ethanol consumption is relevant. Of particular interest in the complex treatment of alcoholic encephalopathy is Chinese hyssop (Lophanthus chinensis), used in Tibetan and Mongolian traditional medicine for liver diseases, as well as a means of improving the functional state of the body and metabolism, slowing down the aging process. Material and methods. Alcohol intoxication was modeled in Wistar rats by per os administration of a 40 % ethanol solution in a volume of 10 ml/kg for six weeks. The L. chinensis dry extract at a dose of 100 mg/kg was administered to animals per os starting from the third week, an hour after ethanol. On day 45, the content of malondialdehyde (MDA), reduced glutathione (GSH), activity of catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase, NADH dehydrogenase and succinate dehydrogenase complex, concentration of ATP werei determined spectrophotometrically in the animal brain homogenate. Results. It was found that L. chinensis extract increases the activity of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase (by 10 %, р = 0.016, by 31 %, р = 0.001, by 30 %, р = 0.041, by 29 %, р = 0.009, respectively) and GSH content (by 24 %, р = 0.019), and also reduces the concentration of MDA (by 20 %, р = 0.014) in brain tissue. A decrease in the intensity of oxidative stress enhances the functioning of enzymatic complexes I (by 23 %, р = 0.017) and II of the mitochondrial respiratory chain (by 72 %, р = 0.001) and increases the ATP content (by 23 %, р = 0.029) in the rat’s brain. Conclusions. L. chinensis extract exhibits antioxidant effects and stimulates energy processes in neurodegenerative processes in the brain caused by long-term alcoholism.

1. Jabbari A., Alani B., Arjmand A., Mazoochi T., Kheiripour N., Ardjmand A. Silymarin pretreatment protects against ethanol-induced memory impairment: Biochemical and histopathological evidence. J. Chem. Neuroanat. 2023;132:102310. doi: 10.1016/j.jchemneu.2023.102310

2. Mitoma H., Manto M., Shaikh A.G. Mechanisms of ethanol-induced cerebellar ataxia: Underpinnings of neuronal death in the cerebellum. Int. J. Environ. Res. Public Health. 2021;18(16):8678. doi: 10.3390/ijerph18168678

3. Nutt D., Hayes A., Fonville L., Zafar R., Palmer E.O.C., Paterson L., Lingford-Hughes A. Alcohol and the brain. Nutrients. 2021;13(11):3938. doi: 10.3390/nu13113938

4. Fairbanks J., Umbreit A., Kolla B.P., Karpyak V.M., Schneekloth T.D., Loukianova L.L., Sinha S. Evidence-basedpharmacotherapiesforalcoholusedisorder: clinical pearls. Mayo Clin. Proc. 2020;95(9):1964–1977. doi: 10.1016/j.mayocp.2020.01.030

5. Pervin Z., Stephen J.M. Effect of alcohol on the central nervous system to develop neurological disorder: Pathophysiological and lifestyle modulation can be potential therapeutic options for alcohol-induced neurotoxication. AIMS Neurosci. 2021;8(3):390–413. doi: 10.3934/Neuroscience.2021021

6. Tsermpini E.E., Plemenitaš Ilješ A., Dolžan V. Alcohol-induced oxidative stress and the role of antioxidants in alcohol use disorder: A systematic review. Antioxidants (Basel). 2022;11(7):1374. doi: 10.3390/antiox11071374

7. Aseeva T.A., Dashiev D.B., Dashiev A.D., Nikolaev S.M., Surkova N.A., Chekhirova G.V., Yurina T.A. Tibetan medicine among the Buryats. Novosibirsk, 2008. 324 p. [In Russian].

8. Batorova S.M., Yakovlev G.P., Aseeva T.A. Directory of medicinal plants of traditional Tibetan medicine. Novosibirsk: Nauka, 2013. 292 p. [In Russian].

9. Tanaka N., Kashiwada Y. Phytochemical studies on traditional herbal medicines based on the ethnopharmacological information obtained by field studies. J. Nat. Med. 2021;75(4):762–783. doi: 10.1007/s11418-021-01545-7

10. Razuvaeva Ya.G., Toropova A.A., Olennikov D.N., Kharzheev D.V. Antihypoxic activity of the dry extract from Nepeta multifida L. Nat. Prod. Res. 2022;36(12):3105–3109. doi: 10.1080/14786419.2021.1935932

11. Sharma A., Cooper R., Bhardwaj G., Cannoo D.S. The genus Nepeta: Traditional uses, phytochemicals and pharmacological properties. J. Ethnopharmacol. 2021;268:113679. doi: 10.1016/j.jep.2020.113679

12. Süntar I., Nabavi S.M., Barreca D., Fischer N., Efferth T. Pharmacological and chemical features of Nepeta L. genus: Its importance as a therapeutic agent. Phytother. Res. 2018;32(2):185–198. doi: 10.1002/ptr.5946

13. Razuvaeva Ya.G., Khaltagarova E.D., Toropova A.A., Markova K.V., Olennikov D.N. Influence of Lophanthus chinensis dry extract on the morphofunctional state of Wistar rats the brain during long-term alcoholization. Voprosy biologicheskoy, meditsinskoy i farmatsevticheskoy khimii = Problems of biological, medicinal and pharmaceutical chemistry. 2024;27(5):65–71. [In Russian]. doi: 10.29296/25877313-2024-05-08

14. Dashinamzhilov Zh.B., Lonshakova K.S., Ubasheev I.O., Nikolaev S.M., GulevichA.A.Aneuroprotective effect of the herbal drug neurofit in alcoholic intoxication. Patologicheskaya fiziologiya i eksperimental’naya terapiya = Pathological Physiology and Experimental Therapy. 2007;(4):27–29. [In Russian].

15. Kamyshnikov V.S. Handbook of clinical and biochemical studies and laboratory diagnostics. Moscow: MEDpress-inform, 2009. 896 p. [In Russian].

16. Boriskin P., Gulenko O., Deviatkin A., Pavlova O., Toropovskiy A. Correlation of superoxide dismutase activity distribution in serum and tissues of small experimental animals. IOP Conf. Ser: Earth Environ. Sci. 2009;403. doi: 10.1088/1755-1315/403/1/012112

17. Girin S.V. Modification of the method for determining catalase activity in biological substrates. Laboratornaya diagnostika = Laboratory Diagnostics. 1999;(4):45–46. [In Russian].

18. Pinto R.E., Bartley W. The effect of age and sex on glutathione reductase and glutation peroxidase activities and aerobic glutathione oxidation in rat liver homogenates. Biochem. J. 1969;112(1):109–115. doi: 10.1042/bj1120109

19. Shaik I.H., Mehvar R. Rapid determination of reduced and oxidized glutathione levels using a new thiol-masking reagent and the enzymatic recycling method: Application to the rat liver and bile samples. Anal. Bioanal. Chem. 2006;385:105–113. doi: 10.1007/s00216-006-0375-8

20. Pollard A.K., Craig E.L., Chakrabarti L. Mitochondrial complex I activity measured by spectrophotometry is reduced across all brain regions in ageing and more specifically in neurodegeneration. PLoS Оne. 2016;11(6):e0157405. doi: 10.1371/journal.pone.0157405

21. Spinazzi M., Casarin A., Pertegato V., Salviati L., Angelini C. Assessment of mitochondrial respiratory chain enzymatic activities on tissues and cultured cells. Nat. Protoc. 2012;7(6):1235–1246. doi: 10.1038/nprot.2012.058

22. Methods of biochemical research. Ed. M.I. Prokhorova. Leningrad, 1982. 272 p. [In Russian].

23. Oliveira de Araújo Melo C., Cidália Vieira T., Duarte Gigonzac M.A., Soares Fortes J., Moreira Duarte S.S., da Cruz A.D., Silva D.M.E. Evaluation of polymorphisms in repair and detoxification genes in alcohol drinkers and non-drinkers using capillary electrophoresis. Electrophoresis. 2020;41(3-4):254–258. doi: 10.1002/elps.201900193

24. Kamal H., Tan G.C., Ibrahim S.F., Shaikh M.F., Mohamed I.N., Mohamed R.M.P., Hamid A.A., Ugusman A., Kumar J. Alcohol use disorder, neurodegeneration, Alzheimer’s and Parkinson’s disease: Interplay between oxidative stress, neuroimmune response and excitotoxicity. Front. Cell. Neurosci. 2020;14:282. doi: 10.3389/fncel.2020.00282

25. Yan T., Zhao Y. Acetaldehyde induces phosphorylation of dynamin-related protein 1 and mitochondrial dysfunction via elevating intracellular ROS and Ca2+ levels. Redox. Biol. 2020;28:101381. doi: 10.1016/j.redox.2019.101381

26. Olennikov D.N., Chirikova N.K., Tankhaeva L.M. Chemical study of Lophanthus chinensis. Chem. Nat. Comp. 2010;46(2):301–302. doi: 10.1007/s10600-010-9596-3

27. Olennikov D.N., Tankhaeva L.M., Rokhin A.V. Lamiaceae carbohydrates. VI. Water-soluble polysaccharides from Lophanthus chinensis. Chem. Nat. Comp. 2008;45(3):300–303. doi: 10.1007/s10600-009-9358-2

28. Tian C., Liu X., Chang Y., Wang R., Lv T., Cui C., Liu M. Investigation of the anti-inflammatory and antioxidant activities of luteolin, kaempferol, apigenin and quercetin. South African Journal of Botany. 2021;137(3):257–264. doi: 10.1016/j.sajb.2020.10.022

29. Kashyap P., Shikha D., Thakur M., Aneja A. Functionality of apigenin as a potent antioxidant with emphasis on bioavailability, metabolism, action mechanism and in vitro and in vivo studies: A review. J. Food Biochem. 2022;46(4):e13950. doi: 10.1111/jfbc.13950

30. Muruganathan N., Dhanapal A.R., Baskar V., Muthuramalingam P., Selvaraj D., Aara H., Shiek Abdullah M.Z., Sivanesan I. Recent updates on source, biosynthesis, and therapeutic potential of natural flavonoid luteolin: A review. Metabolites. 2022;12(11):1145. doi: 10.3390/metabo12111145

31. Antika L.D., Tasfiyati A.N., Hikmat H., Septama A.W. Scopoletin: a review of its source, biosynthesis, methods of extraction, and pharmacological activities. Z. Naturforsch. C. J. Biosci. 2022;77(7-8):303–316. doi: 10.1515/znc-2021-0193

32. Gao X.Y., Li X.Y., Zhang C.Y., Bai C.Y. Scopoletin: a review of its pharmacology, pharmacokinetics, and toxicity. Front. Pharmacol. 2024;15:1268464. doi: 10.3389/fphar.2024.1268464

33. Noor S., Mohammad T., Rub M.A., Raza A., Azum N., Yadav D.K., Hassan M.I., Asiri A.M. Biomedical features and therapeutic potential of rosmarinic acid. Arch. Pharm. Res. 2022;45(4):205–228. doi: 10.1007/s12272-022-01378-2

34. Pavlíková N. Caffeic acid and diseases-mechanisms of action. Int. J. Mol. Sci. 2022;24(1):588. doi: 10.3390/ijms24010588

35. Hasanein P., Seifi R., Hajinezhad M.R., Emamjomeh A. Rosmarinic acid protects against chronic ethanol-induced learning and memory deficits in rats. Nutr. Neurosci. 2017;20(9):547–554. doi: 10.1080/1028415X.2016.1203125

36. Abdul-Muneer P.M., Alikunju S., Mishra V., Schuetz H., Szlachetka A.M., Burnham E.L., Haorah J. Activation of NLRP3 inflammasome by cholesterol crystals in alcohol consumption induces atherosclerotic lesions. Brain. Behav. Immun. 2017;62:291–305. doi: 10.1016/j.bbi.2017.02.014