The Anticonvulsant and Antioxidant Effect of Rosa Moschata (J) Fruit Extract in Pentylenetetrazole induced Epileptic Mouse Model

Authors

  • Zainab Irshad Khyber Medical Unveristy
  • Dr. Samia Nawaz Khyber Medical Unveristy
  • Dr. Shakir Ullah Khyber Medical Unveristy
  • Dr. Niaz Ali Khyber Medical Unveristy
  • Imran Khan Khyber Medical Unveristy
  • Dr. Muhammad Nabi Khyber Medical Unveristy

DOI:

https://doi.org/10.59736/IJP.22.02.900

Keywords:

Epilepsy, GABAA, , oxidative stress, , maze test, , morris test, , water model test, , pentylenetetrazole, , rosa moschata,

Abstract

Background: Rosa moschata (J) (RM (J)) is widely used as a traditional medicine in different ailments including central nervous system diseases, hepatic and gastrointestinal disease. The current study focused on the anticonvulsant effects and memory improvement property of RM (J) fruit extract by the modulation of oxidative stress markers and GABAA receptor in pentylenetetrazole (PTZ) induced mice epileptic model. Methods: The epileptic mice model was developed using pentylenetetrazole (35 mg/kg). The extract were used at doses of 50 mg/kg, 100 mg/kg and 150 mg/kg. The seizure was evaluated according to the Racine Scale. Cognitive functions were evaluated using the Y Maze and Morris Water Maze behavioral tests. The antioxidant effect of RM (J) extract was measured by assessing the level of lipid peroxidation (LPO), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT). Additionally, the effect of RM (J) extract on the expression of GABAA receptors was evaluated using the qPCR. Results: RM (J) fruit extract exhibited a significant (P<0.5) dose-dependent improvement in memory compared to the mice treated with PTZ. Furthermore, the RM (J) extract significantly increased the levels of GSH and CAT and reduced LPO level compared to the PTZ group. The onset time of seizure was prolong while duration of seizure was significantly short in RM (J) extract treated group compared to PTZ group. Interestingly, there was a significant increase in the expression of GABAA receptors in the groups treated with the RM (J) extract, compared to the PTZ group. Conclusions: RM (J) extracts showed anticonvulsant effect and memory improvement potential due to the reduction of oxidative stress markers and enhanced in the expression of GABAA receptors.

Author Biographies

  • Zainab Irshad, Khyber Medical Unveristy

    PhD Scholar, Institute of Pharmaceutical Sciences, Khyber Medical University

  • Dr. Shakir Ullah, Khyber Medical Unveristy

    Assistant Professor, Institute of Pharmaceutical Sciences, Khyber Medical University

  • Dr. Niaz Ali, Khyber Medical Unveristy

    Professor, Institute of Pharmaceutical Sciences, Khyber Medical University

  • Imran Khan, Khyber Medical Unveristy

    Biotechnologist, Institute of Pharmaceutical Sciences, Khyber Medical University

  • Dr. Muhammad Nabi, Khyber Medical Unveristy

    Lecturer, Institute of Pharmaceutical Sciences, Khyber Medical University

References

Devinsky O, Vezzani A, O'Brien TJ, Jette N, Scheffer IE, de Curtis M, et al. Epilepsy. Nat Rev Dis Primers. 2018;4:18024.

Peek SI, Twele F, Meller S, Packer RMA, Volk HA. Epilepsy is more than a simple seizure disorder: Causal relationships between epilepsy and its comorbidities. The Veterinary Journal. 2024;303:106061.

Parsons ALM, Bucknor EMV, Castroflorio E, Soares TR, Oliver PL, Rial D. The Interconnected Mechanisms of Oxidative Stress and Neuroinflammation in Epilepsy. Antioxidants. 2022;11(1):157.

Frantseva MV, Perez Velazquez JL, Tsoraklidis G, Mendonca AJ, Adamchik Y, Mills LR, et al. Oxidative stress is involved in seizure-induced neurodegeneration in the kindling model of epilepsy. Neuroscience. 2000;97(3):431-5.

Vezzani A, Dingledine R, Rossetti AO. Immunity and inflammation in status epilepticus and its sequelae: possibilities for therapeutic application. Expert review of neurotherapeutics. 2015;15(9):1081-92.

Rowley S, Patel M. Mitochondrial involvement and oxidative stress in temporal lobe epilepsy. Free Radical Biology and Medicine. 2013;62:121-31.

Hassanzadeh P, Arbabi E, Atyabi F, Dinarvand R. Ferulic acid exhibits antiepileptogenic effect and prevents oxidative stress and cognitive impairment in the kindling model of epilepsy. Life Sciences. 2017;179:9-14.

Waldbaum S, Patel M. Mitochondrial dysfunction and oxidative stress: a contributing link to acquired epilepsy? Journal of bioenergetics and biomembranes. 2010;42:449-55.

Shekh-Ahmad T, Kovac S, Abramov A, Walker M. Reactive oxygen species in status epilepticus. Epilepsy & behavior. 2019;101:106410.

Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. Journal of ethnopharmacology. 2005;100(1-2):72-9.

Kumar KH, Tamatam A, Pal A, Khanum F. Neuroprotective effects of Cyperus rotundus on SIN-1 induced nitric oxide generation and protein nitration: ameliorative effect against apoptosis mediated neuronal cell damage. Neurotoxicology. 2013;34:150-9.

Shim JS, Kim HG, Ju MS, Choi JG, Jeong SY, Oh MS. Effects of the hook of Uncaria rhynchophylla on neurotoxicity in the 6-hydroxydopamine model of Parkinson's disease. Journal of Ethnopharmacology. 2009;126(2):361-5.

El Omri A, Han J, Yamada P, Kawada K, Abdrabbah MB, Isoda H. Rosmarinus officinalis polyphenols activate cholinergic activities in PC12 cells through phosphorylation of ERK1/2. Journal of ethnopharmacology. 2010;131(2):451-8.

Sasaki K, El Omri A, Kondo S, Han J, Isoda H. Rosmarinus officinalis polyphenols produce anti-depressant like effect through monoaminergic and cholinergic functions modulation. Behavioural Brain Research. 2013;238:86-94.

Lo W-Y, Tsai F-J, Liu C-H, Tang N-Y, Su S-Y, Lin S-Z, et al. Uncaria rhynchophylla upregulates the expression of MIF and cyclophilin A in kainic acid-induced epilepsy rats: a proteomic analysis. The American journal of Chinese medicine. 2010;38(04):745-59.

Carro-Juárez M, Rodríguez-Landa JF, de Lourdes Rodríguez-Peña M, de Jesús Rovirosa-Hernández M, García-Orduña F. The aqueous crude extract of Montanoa frutescens produces anxiolytic-like effects similarly to diazepam in Wistar rats: involvement of GABAA receptor. Journal of Ethnopharmacology. 2012;143(2):592-8.

Hooper L, Kroon PA, Rimm EB, Cohn JS, Harvey I, Le Cornu KA, et al. Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. The American journal of clinical nutrition. 2008;88(1):38-50.

Kardum N, Takić M, Šavikin K, Zec M, Zdunić G, Spasić S, et al. Effects of polyphenol-rich chokeberry juice on cellular antioxidant enzymes and membrane lipid status in healthy women. Journal of Functional Foods. 2014;9:89-97.

Arts IC, Hollman PC. Polyphenols and disease risk in epidemiologic studies. The American journal of clinical nutrition. 2005;81(1):317S-25S.

Barkatullah B, Ibrar M. Plants profile of malakand pass hills, district malakand, Pakistan. African Journal of Biotechnology. 2011;10(73):16521-35.

Sharma B, Singh B, Dhyani D, Verma PK, Karthigeyan S. Fatty acid composition of wild growing rose species. J Med Plants Res. 2012;6:1046-9.

Honarvar M, Javidnia K, Khosh-Khui M. Essential oil composition of fresh and dried flowers of Rosa moschata from Iran. Chemistry of Natural Compounds. 2011;47:826-8.

Ali N, Alam H, Khan A, Ahmed G, Shah WA, Nabi M, et al. Antispasmodic and antidiarrhoeal activity of the fruit of Rosa moschata (J). BMC Complement Altern Med. 2014;14:485.

Hossain MA, Weli AM, Ahmed SHI. Comparison of total phenols, flavonoids and antioxidant activity of various crude extracts of Hyoscyamus gallagheri traditionally used for the treatment of epilepsy. Clinical Phytoscience. 2019;5(1):20.

Kültür Ş. Medicinal plants used in Kırklareli Province (Turkey). Journal of Ethnopharmacology. 2007;111(2):341-64.

Nazir N, Khalil AAK, Nisar M, Zahoor M, Ahmad S. HPLC-UV characterization, anticholinesterase, and free radical-scavenging activities of Rosa moschata Herrm. leaves and fruits methanolic extracts. Brazilian Journal of Botany. 2020;43:523-30.

Kumar N, Bhandari P, Singh B, Bari SS. Antioxidant activity and ultra-performance LC-electrospray ionization-quadrupole time-of-flight mass spectrometry for phenolics-based fingerprinting of Rose species: Rosa damascena, Rosa bourboniana and Rosa brunonii. Food and Chemical Toxicology. 2009;47(2):361-7.

Shashni S, Sharma S. Antioxidant activities of dried wild rosehips (Rosa moschata) of Kullu Valley, Northwestern Indian Himalaya. Indian Journal of Natural Products and Resources (IJNPR)[Formerly Natural Product Radiance (NPR)]. 2022;13(3):339-45.

Ayati Z, Amiri MS, Ramezani M, Delshad E, Sahebkar A, Emami SA. Phytochemistry, traditional uses and pharmacological profile of rose hip: A review. Current pharmaceutical design. 2018;24(35):4101-24.

Sapkota B, Devkota HP, Poudel A, Poudel P, Thapa R. Chapter 35 - Rosa spp. (Rosa canina L., R. macrophylla Lindl., R. moschata Herrm., R. multiflora Thunb.). In: Belwal T, Bhatt I, Devkota H, editors. Himalayan Fruits and Berries: Academic Press; 2023. p. 371-81.

Ouerghemmi S, Sebei H, Siracusa L, Ruberto G, Saija A, Cimino F, et al. Comparative study of phenolic composition and antioxidant activity of leaf extracts from three wild Rosa species grown in different Tunisia regions: Rosa canina L., Rosa moschata Herrm. and Rosa sempervirens L. Industrial Crops and Products. 2016;94:167-77.

Ali N, Alam H, Khan A, Ahmed G, Shah WA, Nabi M, et al. Antispasmodic and antidiarrhoeal activity of the fruit of Rosa moschata (J). BMC complementary and alternative medicine. 2014;14(1):1-6.

Jamal M, ur Rehman M, Nabi M, Awan AA, Ali N, Sherkheli MA, et al. Evaluation of safety profile and stress suppressant activity of Rosa moschata in mice. Pak J Pharm Sci. 2019;32(6):2659-65.

Bhandary SK, Bhat VS, Sharmila K, Bekal MP. Preliminary phytochemical screening of various extracts of Punica granatum peel, whole fruit and seeds. Journal of Health and Allied Sciences NU. 2012;2(04):34-8.

Shimada T, Yamagata K. Pentylenetetrazole-Induced Kindling Mouse Model. Journal of visualized experiments : JoVE. 2018(136).

Van Erum J, Van Dam D, De Deyn PP. PTZ-induced seizures in mice require a revised Racine scale. Epilepsy & behavior : E&B. 2019;95:51-5.

Van Erum J, Van Dam D, De Deyn PP. PTZ-induced seizures in mice require a revised Racine scale. Epilepsy & Behavior. 2019;95:51-5.

Kraeuter A-K, Guest PC, Sarnyai Z. The Y-maze for assessment of spatial working and reference memory in mice. Pre-clinical models: Springer; 2019. p. 105-11.

Zakria M, Ahmad N, Al Kury LT, Alattar A, Uddin Z, Siraj S, et al. Melatonin rescues the mice brain against cisplatin-induced neurodegeneration, an insight into antioxidant and anti-inflammatory effects. Neurotoxicology. 2021;87:1-10.

Draper HH, Hadley M. [43] Malondialdehyde determination as index of lipid Peroxidation. Methods in enzymology. 186: Elsevier; 1990. p. 421-31.

Pires LF, Costa LM, de Almeida AAC, Silva OA, Cerqueira GS, de Sousa DP, et al. Is there a correlation between in vitro antioxidant potential and in vivo effect of carvacryl acetate against oxidative stress in mice hippocampus? Neurochemical research. 2014;39(4):758-69.

Ellman GL. Tissue sulfhydryl groups. Archives of biochemistry and biophysics. 1959;82(1):70-7.

Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. The Journal of laboratory and clinical medicine. 1963;61:882-8.

Czeczot H, Scibior D, Skrzycki M, Podsiad M. Glutathione and GSH-dependent enzymes in patients with liver cirrhosis and hepatocellular carcinoma. Acta biochimica Polonica. 2006;53(1):237-42.

Nelson DP, Kiesow LA. Enthalpy of decomposition of hydrogen peroxide by catalase at 25 degrees C (with molar extinction coefficients of H 2 O 2 solutions in the UV). Analytical biochemistry. 1972;49(2):474-8.

Livak KJ, Schmittgen TD. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method. Methods. 2001;25(4):402-8.

Obay BD, Taşdemir E, Tümer C, Bilgin HM, Atmaca M. Dose dependent effects of ghrelin on pentylenetetrazole-induced oxidative stress in a rat seizure model. Peptides. 2008;29(3):448-55.

Khatami P, Mirazi N, Khosravi M, Bananej M. Anticonvulsant activity of oxaprozin in a rat model of pentylenetetrazole-induced seizure by targeting oxidative stress and SIRT1/PGC1α signaling. Canadian Journal of Physiology and Pharmacology. 2022.

Hoyos CM, Stephen C, Turner A, Ireland C, Naismith SL, Duffy SL. Brain oxidative stress and cognitive function in older adults with diabetes and pre-diabetes who are at risk for dementia. Diabetes Research and Clinical Practice. 2022;184:109178.

Ren Y, Sun-Waterhouse D, Ouyang F, Tan X, Li D, Xu L, et al. Apple phenolic extracts ameliorate lead-induced cognitive impairment and depression-and anxiety-like behavior in mice by abating oxidative stress, inflammation and apoptosis via the miR-22-3p/SIRT1 axis. Food & Function. 2022;13(5):2647-61.

Seigers R, Fardell JE. Neurobiological basis of chemotherapy-induced cognitive impairment: A review of rodent research. Neuroscience & Biobehavioral Reviews. 2011;35(3):729-41.

Jahanbani R, Bahramnejad E, Rahimi N, Shafaroodi H, Sheibani N, Moosavi-Movahedi AA, et al. Anti-seizure effects of walnut peptides in mouse models of induced seizure: The involvement of GABA and nitric oxide pathways. Epilepsy Research. 2021;176:106727.

Scheuer T, Endesfelder S, auf dem Brinke E, Bührer C, Schmitz T. Neonatal Oxidative Stress Impairs Cortical Synapse Formation and GABA Homeostasis in Parvalbumin-Expressing Interneurons. Oxidative Medicine and Cellular Longevity. 2022;2022:8469756.

Tu J, Jin Y, Zhuo J, Cao X, Liu G, Du H, et al. Exogenous GABA improves the antioxidant and anti-aging ability of silkworm (Bombyx mori). Food Chemistry. 2022;383:132400.

Alharbi KS. Anticonvulsant effects of desvenlafaxine on modulating brain monoamine and oxidative stress in mice. Brazilian Journal of Biology. 2021;83.

Mohamed HM, Mahmoud AM. Chronic exposure to the opioid tramadol induces oxidative damage, inflammation and apoptosis, and alters cerebral monoamine neurotransmitters in rats. Biomedicine & Pharmacotherapy. 2019;110:239-47.

Abou Seif HS. Physiological changes due to hepatotoxicity and the protective role of some medicinal plants. Beni-Suef University Journal of Basic and Applied Sciences. 2016;5(2):134-46.

Ali N, Alam H, Khan A, Ahmed G, Shah WA, Nabi M, et al. Antispasmodic and antidiarrhoeal activity of the fruit of Rosa moschata (J). BMC Complement Altern Med. 2014;14:485-.

Downloads

Published

2024-09-15

Issue

Section

Original article

How to Cite

1.
Irshad Z, Nawaz S, Ullah S, Ali N, Khan I, Nabi M. The Anticonvulsant and Antioxidant Effect of Rosa Moschata (J) Fruit Extract in Pentylenetetrazole induced Epileptic Mouse Model. Int J Pathol [Internet]. 2024 Sep. 15 [cited 2024 Sep. 27];22(2):61-75. Available from: https://jpathology.com/index.php/OJS/article/view/900

Most read articles by the same author(s)