Effects of Khaya anthotheca against behavioral disorders and oxidative stress induced by repeated variable stress

Franklin Gamo Zemo , Sefirin Djiogue , Yolande Sandrine Ngadena Mengue , Charline Florence Awounfack , Rudig Nikanor Tadah Djikem , Constant Anatole Pieme , Dieudonne Njamen

Exploration of Drug Science ›› 2025, Vol. 3 ›› Issue (1) : 1008127

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Exploration of Drug Science ›› 2025, Vol. 3 ›› Issue (1) :1008127 DOI: 10.37349/eds.2025.1008127
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Effects of Khaya anthotheca against behavioral disorders and oxidative stress induced by repeated variable stress
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Abstract

Aim: Menopausal women are suffering from stress-related disorders, and in the previous studies, Khaya anthotheca (K. anthotheca) decoction exhibited estrogenic and anxiolytic properties. Taken together, the aim of this study was to evaluate the effects of K. anthotheca decoction on behavioral disorders and oxidative stress induced by repeated variable stress in ovariectomized Wistar rats.

Methods: Forty-two female Wistar rats (10–12 weeks old; 145 ± 10 g) were used. They were ovariectomized (except those from the sham operated group). Fourteen days after ovariectomy, animals were randomly distributed into 7 groups (n = 6): sham operated and negative control groups receiving distilled water; two positive control groups receiving estradiol valerate and diazepam (1 mg/kg each), and three other groups receiving the tested doses of K. anthotheca extract (125, 250, and 500 mg/kg each). The treatment was applied every week. Anxiety, depression, and motor coordination were assessed throughout the experimental procedure. The anti-oxidative potential of the extract was evaluated in rat brain homogenate.

Results: It was noted that K. anthotheca extract induced anxiolytic effects marked by an increase in the locomotory activity during open field, light/dark, and elevated plus maze tests. Besides, its anti-depressive effects were shown by a significant (p < 0.05) decrease in the immobilization time during the forced swimming test. By improving the suspension time during grid and wire grip tests, the distance covered, and the number of switch directions during the beam walking test, the extract increased motor coordination. The antioxidant potential of the extract was marked by a significant decrease ( p < 0.01) in malondialdehyde level and an increase ( p < 0.05) in reduced glutathione level.

Conclusions: These results provide valuable insights into the potential therapeutic application of the K. anthotheca extract; however, more studies are needed to elucidate mechanisms of action.

Keywords

menopause / ovariectomy / repeated variable stress model / Khaya anthotheca / behavioral improvement / motor coordination improvement / antioxidant activity

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Franklin Gamo Zemo, Sefirin Djiogue, Yolande Sandrine Ngadena Mengue, Charline Florence Awounfack, Rudig Nikanor Tadah Djikem, Constant Anatole Pieme, Dieudonne Njamen. Effects of Khaya anthotheca against behavioral disorders and oxidative stress induced by repeated variable stress. Exploration of Drug Science, 2025, 3 (1) : 1008127 DOI:10.37349/eds.2025.1008127

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References

[1]

Stevenson JC. A woman’s journey through the reproductive, transitional and postmenopausal periods of life: impact on cardiovascular and musculo—skeletal risk and the role of estrogen replacement. Maturitas. 2011; 70: 197-205.

[2]

Supriya S, Kamini CT. Stress and well—being in menopausal and post—menopausal working and non—working women. Ind J Appl Res. 2014; 4: 559-63.

[3]

Ketcha WGJM, Zemo GF, Djiogue S, Awounfack CF, Njamen D. Estrogenic and anxiolytic effects of the decoction of stem bark of Khaya anthotheca (Welw.) C.DC (Meliaceae) in ovariectomised Wistar rats. Inter J Phytomed. 2017; 9: 241—52.

[4]

Zemo GF, Djiogue S, Ketcha WGJM, Seke EPF, Yonkeu TFG, Djikem TRN, et al. Fourteen days post—ovariectomy estrogens decline is associated with anxiogenic effects on Wistar rats. J Pharm Pharmacol. 2017; 5: 869-76.

[5]

Zemo GF, Djiogue S, Tchoupang NE, Awounfack CF, Djikem TRN, Ndjengue MEL, et al. Anxiolytic, estrogenic and non—toxic effects of sub—acute treatment with Khaya anthotheca (Welw.) C.DC (Meliaceae) decoction in ovariectomized Wistar rats. J Biol Pharm Chem Res. 2023; 10: 39-55.

[6]

Djiogue S, Djiyou DAB, Seke EPF, Ketcha WGJM, Djikem TRN, Njamen D. Memory an exploration bihavior impairment in ovariectomized Wistar rats. Behav Brain Funct. 2018; 14: 14.

[7]

Tucker JS, Sinclair RR, Mohr CD, Adler AB, Thomas JL, Salvi AD. A temporal investigation of the direct, interactive, and reverse relations between demand and control and affective strain. Work & Stress. 2008; 22: 81-95.

[8]

Davidson KW, Mostofsky E, Whang W. Don’t worry, be happy: positive affect and reduced 10—year incident coronary heart disease: the Canadian Nova Scotia Health Survey. Eur Heart J. 2010; 31: 1065-70.

[9]

Kuti D, Winkler Z, Horváth K, Juhász B, Szilvásy—Szabó A, Fekete C, et al. The metabolic stress response: Adaptation to acute—, repeated— and chronic challenges in mice. iScience. 2022; 25: 104693.

[10]

Nair BB, Aung ZK, Porteous R, Prescott M, Glendining KA, Jenkins DE, et al. Impact of chronic variable stress on neuroendocrine hypothalamus and pituitary in male and female C57BL/6J mice. J Neuroendocrinol. 2021; 33: e12972.

[11]

Umland EM, Cauffield JS, Kirk JK, Thomason TE. Phytoestrogens as therapeutic alternatives to traditional hormone replacement in postmenopausal women. Pharmacotherapy. 2000; 20: 981—90.

[12]

O’brien CP. Benzodiazepine use, abuse, and dependence. J Clin Psychiatry. 2005; 66: 28-33.

[13]

Pitkin J. Alternative and complementary therapies for the menopause. Menopause Int. 2012; 18: 20-7.

[14]

Franklin ZG, Ladagu AD, Magloire KWGJ, Folarin OR, Sefirin D, Tashara TG, et al. Ameliorative effects of the aqueous extract of Khaya anthotheca (Welw.) C.DC (Meliaceae) in vanadium induced anxiety, memory loss and pathologies in the brain and ovary of mice. J Ethnopharmacol. 2021; 275: 114099.

[15]

Zemo GF, Djiogue S, Seke EPF, Pieme CA, Babiker AY, Awounfack CF, et al. Neuroprotective effects of Khaya anthotheca (Welw.) C.DC (Meliaceae) decoction on neurodegeneration induced by estrogen depletion in rats. J Exp Pathol. 2021; 2: 174-81.

[16]

Arrant AE, Schramm—Sapyta NL, Kuhn CM. Use of the light/dark test for anxiety in adult and adolescent male rats. Behav Brain Res. 2013; 256: 119-27.

[17]

Yankelevitch—Yahav R, Franko M, Huly A, Doron R. The forced swim test as a model of depressive—like behavior. J Vis Exp. 2015; 97: e52587.

[18]

Nicole H, Kathia J, Margaret AP, Jutatip G, Heidi S, Stacy LS. Detecting behavioral deficits in rat after traumatic brain injury. J Vis Exp. 2018; 131: e56044.

[19]

Hayase T. Depression—related anhedonic behaviors caused by immobilization stress: a comparison with nicotine—induced depression—like behavioral alterations and effects of nicotine and/or “antidepressant” drugs. J Toxicol Sci. 2011; 36: 31-41.

[20]

Baiba J, Zane D, Kaspars J, Vladimirs P, Ulrika B, Ingrida M, et al. Spruce needle polyphenols protect against atorvastatin—induced muscle weakness and do not influence central nervous system function in rats. Pro Lat Aca Sci Section B Nat Exact App Sci. 2016; 70: 13-20.

[21]

Lane NE, Yao W, Kinney JH, Modin G, Balooch M, Wronski TJ. Both hPTH(1—34) and bFGF increase trabecular bone mass in osteopenic rats but they have different effects on trabecular bone architecture. J Bone Miner Res. 2003; 18: 2105—15.

[22]

Wilbur KM, Bernhein F, Schapiro OW. Determination of lipid peroxidation. Arch Biochem Biophy. 1949; 24: 305—10.

[23]

Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959; 82: 70-7.

[24]

Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem. 1996; 239: 70-6.

[25]

Doyle BJ, Frasor J, Bellows LE, Locklear TD, Perez A, Gomez—Laurito J, et al. Estrogenic effects of herbal medicines from Costa Rica used for the management of menopausal symptoms. Menopause. 2009; 16: 748—55.

[26]

Pinkerton JV, Stovall DW, Kightlinger RS. Advances in the treatment of menopausal symptoms. Womens Health (Lond). 2009; 5: 361-84.

[27]

Srivastava DP, Woolfrey KM, Penzes P. Insights into rapid modulation of neuroplasticity by brain estrogens. Pharmacol Rev. 2013; 65: 1318—50.

[28]

Nosek M, Kennedy HP, Beyene Y, Taylor D, Gilliss C, Lee K. The effects of perceived stress and attitudes toward menopause and aging on symptoms of menopause. J Midwifery Womens Health. 2010; 55: 328-34.

[29]

Bum EN, Taiwe GS, Moto FCO, Ngoupaye GT, Nkantchoua GCN, Pelanken MM, et al. Anticonvulsant, anxiolytic, and sedative properties of the roots of Nauclea latifolia Smith in mice. Epilepsy Behav. 2009; 15: 434—40.

[30]

Wanda GJMK, Djiogue S, Gamo FZ, Ngitedem SG, Njamen D. Anxiolytic and sedative activities of aqueous leaf extract of Dichrocephala integrifolia (Asteraceae) in mice. J Ethnopharmacol. 2015; 176: 494-8.

[31]

Bisong SA, Brown R, Osim EE. Comparative effects of Rauwolfia vomitoria and chlorpromazine on locomotor behaviour and anxiety in mice. J Ethnopharmacol. 2010; 132: 334—9.

[32]

Bourin M, Hascoët M. The mouse light/dark box test. Eur J Pharmacol. 2003; 463: 55-65.

[33]

Rammal H, Soulimani R. Effects of high doses of Gelsemium sempervirens L. on GABA receptor and on the cellular and humoral immunity in mice. J Med Sci. 2010; 1: 40-4.

[34]

Depression [Internet]. WHO; c2025 [cited 2024 Jan 10]. Available from: https://www.who.int/health—topics/depression#tab=tab_1(2024)

[35]

Dar A, Khatoon S. Antidepressant effects of ethanol extract of Areca catechu in rodents. Phytotherapy Research. 1997; 11: 174-6.

[36]

Walia V. Influence of stress and fluoxetine on immobility period of mice in tail suspension test and forced swim test. Asian J Pharm Clin Res. 2016; 9: 302—5.

[37]

Priya N, Vijayalakshmi K, Khadira S. Investigation on the neuroprotective effects of hesperidin on behavioural activities in 6—ohda induced parkinson model. Inter J Phar Biol Sci. 2014; 5: 570-7.

[38]

Djiogue S, Motoum TF, Djikem TRN, Zemo GF, Awounfack CF, Seke EPF, et al. Oestrogen—like and anxiolytic properties of Pueraria phaseoloides extracts on ovariectomized Wistar rat. Biomed Sci & Res. 2020; 28: 21889-99.

[39]

Kuper H, Tzonou A, Kaklamani E, Hsieh CC, Lagiou P, Adami HO, et al. Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma. Int J Cancer. 2000; 85: 498-502.

[40]

Ozgönül M, Oge A, Sezer ED, Bayraktar F, Sözmen EY. The effects of estrogen and raloxifene treatment on antioxidant enzymes in brain and liver of ovarectomized female rats. Endocr Res. 2003; 29: 183-9.

[41]

Grigoriadis S, Kennedy SH. Role of estrogen in the treatment of depression. Am J Ther. 2002; 9: 503— 9.

[42]

Spencer JL, Waters EM, Romeo RD, Wood GE, Milner TA, McEwen BS. Uncovering the mechanisms of estrogen effects on hippocampal function. Front Neuroendocrinol. 2008; 29: 219-37.

[43]

Hylander BL, Repasky EA, Sexton S. Using Mice to Model Human Disease: Understanding the Roles of Baseline Housing—Induced and Experimentally Imposed Stresses in Animal Welfare and Experimental Reproducibility. Animals (Basel). 2022; 12: 371.

[44]

Ososki AL, Kennelly EJ. Phytoestrogens: a review of the present state of research. Phytother Res. 2003; 17: 845-69.

[45]

Daendee S, Thongsong B, Kalandakanond—Thongsong S. Effects of time of estrogen deprivation on anxiety—like behavior and GABAA receptor plasticity in ovariectomized rats. Behav Brain Res. 2013; 246: 86-93.

[46]

Sarma P, Borah M, Das S. Evaluation of the effect of ethanolic extract of fruit pulp of Cassia fistula Linn. on forced swimming induced chronic fatigue syndrome in mice. Res Pharm Sci. 2015; 10: 206—13.

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