EFFECT OF PUMPKIN (CUCURBITA PEPO L.) AND MARIGOLD (TAGETES PATULA L.) EXTRACTS ON HIPPOCAMPAL MITOCHONDRIA FUNCTIONAL ACTIVITY WITHIN CONDITIONS OF EXPERIMENTAL ACUTE BRAIN HYPOMETABOLISM
https://doi.org/10.19163/2307-9266-2019-7-4-198-207
Abstract
The aim of the study is to evaluate the effect of pumpkin (Cucurbita pepo L.) and marigold extracts (Tagetes patula L.) on the hippocampal mitochondria functional activity within the conditions of experimental acute brain hypometabolism.
Materials and methods. The work was performed on 50 male Wistar rats, which reproduced an acute brain hypometabolic state by administration of a 3M sodium azide solution in hippocampus (n = 40 and n = 10 – a group of sham-operated animals). The test extracts and the reference drug – EGb 761 – were prophylactically administered at the dose of 100 mg/kg per os for 10 days. 24 hours after the last administration, sodium azide was injected, the brain was taken, the hippocampus was isolated to obtain a supernatant and determine the parameters of mitochondrial respiration, the intensity of anaerobic processes, the concentration of the apoptosis-inducing factor, endonuclease G, and β-amyloid.
Results. The carried out study established that the prophylactic administration of pumpkin and marigold extracts contributed to the restoration of a mitochondrial function and a decrease in the intensity of anaerobic processes. In the group of the rats treated with pumpkin and marigold extracts, an increase of ATP concentration in the hippocampal supernatant by 65.7% (p<0.002) was observed; it was 66.2% (p><0.002) relative to the animals deprived of pharmacological support. ,When the rats were treated with pumpkin and marigold extracts, a decrease in the concentration of apoptosis-inducing factor (by 33% (p><0.002) and 38.3% (p><0.002), respectively) and endonuclease G (by 3.6 times (p><0.002) and 4.4 times (p><0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p><0.0002) and 54.4% (p><0.0002), respectively. The test-extracts had an equivalent therapeutic efficacy with the reference drug. Conclusion On the basis of the obtained data, it is possible to suggest the prospect of a further study of pumpkin and marigold extracts as the drugs of a targeted correction of cerebral hypometabolism. Keywords: plant extracts, hypometabolism, hippocampus, mitochondria >< 0.002) was observed; it was 66.2% (p<0.002) relative to the animals deprived of pharmacological support. ,When the rats were treated with pumpkin and marigold extracts, a decrease in the concentration of apoptosis-inducing factor (by 33% (p><0.002) and 38.3% (p><0.002), respectively) and endonuclease G (by 3.6 times (p><0.002) and 4.4 times (p><0.002), respectively) was also noted. The adm>< 0.002) relative to the animals deprived of pharmacological support. ,When the rats were treated with pumpkin and marigold extracts, a decrease in the concentration of apoptosis-inducing factor (by 33% (p<0.002) and 38.3% (p><0.002), respectively) and endonuclease G (by 3.6 times (p><0.002) and 4.4 times (p><0.002), respectively) was also noted. The administration of pumpki>< 0.002) and 38.3% (p<0.002), respectively) and endonuclease G (by 3.6 times (p><0.002) and 4.4 times (p><0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p><0.0002) and 54.4% (p><0.0002), respectively. The test-extracts had an equivalent therapeutic efficacy with >< 0.002), respectively) and endonuclease G (by 3.6 times (p<0.002) and 4.4 times (p><0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p><0.0002< 0.002) and 4.4 times (p<0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p><0.0002) and 54.4% (p><0.0002), respectively. The te>< 0.002), respectively) was also noted. The administration of pumpkin and marigold extracts reduced the amyloid β-peptide concentration in the rats’ hippocampus by 54.4% (p<0.0002) and 54.4% (p><0.0002), respectively. The test-extracts had an equiva>< 0.0002) and 54.4% (p<0.0002), respectively. The test-extracts had an equivalent therapeutic efficacy with the reference drug. Conclusion On the basis of the obtained d>< 0.0002), respectively. The test-extracts had an equivalent therapeutic efficacy with the reference drug.
Conclusion On the basis of the obtained data, it is possible to suggest the prospect of a further study of pumpkin and marigold extracts as the drugs of a targeted correction of cerebral hypometabolism.
About the Authors
A. V. VoronkovRussian Federation
Doctor of Science (Med.), professor, head of the department of pharmacology with a course of clinical pharmacology
D. I. Pozdnyakov
Russian Federation
Candidate of l Sciences (Pharm.), Senior Lecturer of the Department of Pharmacology with a course of clinical pharmacology
S. L. Adzhiakhmetova
Russian Federation
PhD, lecturer of the Department of Organic Chemistry
N. M. Chervonnaya
Russian Federation
PhD, lecturer of the Department of Organic Chemistry
K. A. Miroshnichenko
Russian Federation
PhD-student of the Department of Pharmacology with a course of clinical pharmacology
A. V. Sosnovskaya
Russian Federation
5th year student of the Pharmaceutical department
E. I. Chereshkova
Russian Federation
5th year student of the Pharmaceutical department
References
1. Gao C, Chang P, Yang L. Neuroprotective effects of hydrogen sulfide on sodium azide-induced oxidative stress in PC12 cells. Int J Mol Med. 2018; 41(1):242–250. doi:10.3892/ijmm.2017.3227
2. Takahashi RH, Nagao T, Gouras GK. Plaque formation and the intraneuronal accumulation of β-amyloid in Alzheimer’s disease. Pathol Int. 2017; 67:185–193. doi: 10.1111/ pin.12520.
3. Chen GF, Xu TH, Yan Y. Amyloid beta: structure, biology and structure-based therapeutic development. Acta Pharmacol Sin. 2017;38(9): 1205–1235. doi:10.1038/aps.2017.28
4. Lesné SE, Sherman MA, Grant M. Brain amyloid-β oligomers in ageing and Alzheimer’s disease. Brain. 2013; 136, Part 5: 1383–1398. doi:10.1093/brain/awt062
5. Mattson MP. Pathways towards and away from Alzheimer’s disease. Nature.2004; 430(7000): 631–639. doi:10.1038/nature02621.
6. Del Prete D, Suski JM, Oulès B. Localization and Processing of the Amyloid-β Protein Precursor in Mitochondria-Associated Membranes. J Alzheimers Dis. 2017;55(4): 1549–1570. doi:10.3233/JAD-160953
7. Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, Caspersen C, Chen X, Pollak S, Chaney M. Abad directly links a beta to mitochondrial toxicity in Alzheimer’s disease. Science. 2004;304:448–452. doi: 10.1126/science.1091230.
8. Chen X, Yan SD. Mitochondrial abeta: A potential cause of metabolic dysfunction in Alzheimer’s disease. IUBMB Life. 2006;58:686–694. doi: 10.1080/15216540601047767.
9. De Strooper B, Iwatsubo T, Wolfe MS. Presenilins and γ-secretase: structure, function, and role in Alzheimer Disease. Cold Spring Harb Perspect Med. 2012;2(1):a006304. doi:10.1101/cshperspect.a006304
10. Zhao Y, Zhang Y, Pan F. The effects of EGb761 on lipopolysaccharide-induced depressive-like behaviour in C57BL/6J mice. Cent Eur J Immunol. 2015;40(1): 11–17. doi:10.5114/ceji.2015.49427
11. Gordon RYA. Kapralova MV, Goduhin OV, Arhipov VI. Osobennosti narushenij pamyati u krys posle povrezhdeniya polya SA3 dorsal’nogo gippokampa kainovoj kislotoj [Features of memory impairment in rats aſter damage to the CA3 field of the dorsal hippocampus with kainic acid] Bulletin of Experimental Biology and Medicine. 2013;155(6): 771–775 Russian
12. Brouillet E, Hyman BT, Jenkins BG, Henshaw DR, Schulz JB, Sodhi P, Rosen BR, Beal MF.Systemic or local administration of azide produces striatal lesions by an energy impairmentinduced excitotoxic mechanism. Experimental Neurology.1994;129:175–182.
13. Voronkov A.V., Pozdnyakov D.I., Nigaryan S.A., Khouri E.I., Miroshnichenko K.A., Sosnovskaya A.V., Olokhova E.A. Evaluation of the mitochondria respirometric function in the conditions of pathologies of various geneses. Pharmacy & Pharmacology. 2019;7(1):20–31. doi:10.19163/2307-9266-2019-7-1-20-31
14. Riha PD, Rojas JC, Colorado RA, Gonzalez-Lima F. Animal model of posterior cingulate cortex hypometabolism implicated in amnestic MCI and AD. Neurobiol Learn Mem. 2008;90(1):112–124. doi:10.1016/j.nlm.2008.01.011
15. Scheltens NME, van der Weijden K, Adriaanse SM. Hypometabolism of the posterior cingulate cortex is not restricted to Alzheimer’s disease. Neuroimage Clin. 2018;19: 625–632. doi:10.1016/j.nicl.2018.05.024
16. Nicholson RM, Kusne Y, Nowak LA, LaFerla FM, Reiman EM, Valla J. Regional cerebral glucose uptake in the 3xTG model of Alzheimer’s disease highlights common regional vulnerability across AD mouse models. Brain Res. 2010; 1347:179–185. doi:10.1016/j.brainres.2010.05.084
17. Chou JL, Shenoy DV, Thomas N, Choudhary PK, Laferla FM, Goodman SR.Early dysregulation of the mitochondrial proteome in a mouse model of Alzheimer’s disease. Journal of Proteomics. 2011;74(4): 466–479. doi: 10.1016 /j.jprot.2010.12.012.
18. Li Z, Chen X, Lu W. Anti-Oxidative Stress Activity Is Essential for Amanita caesarea Mediated Neuroprotection on Glutamate-Induced Apoptotic HT22 Cells and an Alzheimer’s Disease Mouse Model. Int J Mol Sci. 2017;18(8): 1623. doi:10.3390/ijms18081623
19. Obulesu, M, Jhansi Lakshmi M. Apoptosis in Alzheimer’s disease: an understanding of the physiology, pathology and therapeutic avenues. Neurochemical research . 2014;39(12): 2301–2312.
20. Chételat G, Ossenkoppele R, Villemagne VL. Atrophy, hypometabolism and clinical trajectories in patients with amyloid-negative Alzheimer’s disease. Brain. 2016; 139, Part 9: 2528–2539. doi:10.1093/brain/aww159
21. Sperling R, Mormino E, Johnson K. The evolution of preclinical Alzheimer’s disease: implications for prevention trials. Neuron. 2014; 84(3): 608–622. doi:10.1016/j.neuron.2014.10.038
22. Villain N, Desgranges B, Viader F. Relationships between hippocampal atrophy, white matter disruption, and gray matter hypometabolism in Alzheimer’s disease. J Neurosci. 2008; 28(24): 6174–6181. doi:10.1523/JNEUROSCI.1392-08.2008
23. Cummings J, Aisen PS, DuBois B. Drug development in Alzheimer’s disease: the path to 2025. Alzheimers Res Ther. 2016;8: 39–51 doi:10.1186/s13195-016-0207-9.
24. Henley DB, Sundell KL, Sethuraman G, Dowsett SA, May PC. Safety profile of semagacestat, a gamm-secretase inhibitor: IDENTITY trial findings. Curr Med Res Opin.2014; 10: 2021–2032. doi: 10.1185/03007995.2014.939167.
25. Frenguelli BG. The Purine Salvage Pathway and the Restoration of Cerebral ATP: Implications for Brain Slice Physiology and Brain Injury. Neurochem Res. 2019;44(3):661– 675. doi:10.1007/s11064-017-2386-6
26. Farina B, Di Sorbo G, Chambery A.Structural and biochemical insights of CypA and AIF interaction. Sci Rep. 2017;7(1):1138. doi: 10.1038/s41598-017-01337-8
27. Masters CL, Selkoe DJ. Biochemistry of amyloid β-protein and amyloid deposits in Alzheimer disease. Cold Spring Harb Perspect Med. 2012;2(6): a006262. doi:10.1101/ cshperspect.a006262
Review
For citations:
Voronkov A.V., Pozdnyakov D.I., Adzhiakhmetova S.L., Chervonnaya N.M., Miroshnichenko K.A., Sosnovskaya A.V., Chereshkova E.I. EFFECT OF PUMPKIN (CUCURBITA PEPO L.) AND MARIGOLD (TAGETES PATULA L.) EXTRACTS ON HIPPOCAMPAL MITOCHONDRIA FUNCTIONAL ACTIVITY WITHIN CONDITIONS OF EXPERIMENTAL ACUTE BRAIN HYPOMETABOLISM. Pharmacy & Pharmacology. 2019;7(4):198-207. https://doi.org/10.19163/2307-9266-2019-7-4-198-207