Research Article
BibTex RIS Cite

In silico and animal model study of Cissus quadrangularis stem ethanolic extract for unpredictable spontaneous stress

Year 2026, Volume: 30 Issue: 2, 535 - 552, 15.03.2026
https://doi.org/10.12991/jrespharm.1909318
https://izlik.org/JA97ZU39CD

Abstract

A unique bioresource for folk and herbal remedies from antiquity to the present is Cissus quadrangularis. This study aimed to examine Cissus quadrangularis ethanolic stem extract’s potential as an in vivo anti-stress agent. Molecular docking and ADMET studies reveal good intermolecular interactions of many phytoconstituents with the protein to show drug-like properties. According to acute oral toxicity research, LD50 of ECQ is safe up to 700 mg/kg body per oral (p.o.) weight. Studies on unpredictable spontaneous stress (USS) show a corresponding decline in GSH, SOD, and CAT levels, as well as an increase in MDA and MPO levels compared to normal. The oxidative stress indices in USS models were significantly enhanced by treatment with extract dosages of 300 and 500 mg/kg. According to the results, MDA was considerably increased by USS (5.219 ± 0.156) compared to the control group’s MDA (2.984 ± 0.172). MDA levels were considerably reduced by both extract treatments (4.117 ± 0.165 and 3.889 ± 0.07, respectively; Gerifortetreated group: 3.171 ± 0.139). Histopathological study of extracts 300 and 500 mg/kg shows positive effects. These outcomes imply that extract was crucial in preventing oxidative damage following strenuous exercise, and the lower serum MPO levels might be the result of enhanced neutrophil intracellular redox conditions. As a result, our research strengthens the drug's current therapeutic potential for anti-stress or apoptogenic action and offers solid evidence in favor of its clinical application in contemporary medicine.

References

  • [1] Taleuzzaman M, Jain P, Verma R, Iqbal Z, Mirza MA. Eugenol as a Potential Drug Candidate: A Review. Curr Top Med Chem. 2021;21(20):1804-1815. https://doi.org/10.2174/1568026621666210701141433.
  • [2] Karimi A, Majlesi M, Rafieian-Kopaei M. Herbal versus synthetic drugs; beliefs and facts. J Nephropharmacol. 2015;4(1):27-30.
  • [3] Lazarev NV. General and specific in action of pharmacological agents. Farmacol Toxicol. 1958;21(3):81-86.
  • [4] McEwen BS, Bowles NP, Gray JD, Hill MN, Hunter RG, Karatsoreos IN, Nasca C. Mechanisms of stress in the brain. Nature neuroscience. 2015;18(10):1353-1363. https://doi.org/10.1038/nn.4086
  • [5] Govindarajan A, Rao BS, Nair D, Trinh M, Mawjee N, Tonegawa S, Chattarji S. Transgenic brain-derived neurotrophic factor expression causes both anxiogenic and antidepressant effects. Proceed Nat Acad Sci. 2006;103(35):13208-13213. https://doi.org/10.1073/pnas.0605180103
  • [6] Pawlak R, Rao BS, Melchor JP, Chattarji S, McEwen B, Strickland S. Tissue plasminogen activator and plasminogen mediate stress-induced decline of neuronal and cognitive functions in the mouse hippocampus. . Proceed Nat Acad Sci. 2005;102(50):18201-18206. https://doi.org/10.1073/pnas.0509232102
  • [7] Chen Y, Fenoglio KA, Dubé CM, Grigoriadis DE, Baram TZ. Cellular and molecular mechanisms of hippocampal activation by acute stress are age-dependent. Mol Psychiatry. 2006;11(11):992-1002. https://doi.org/10.1038/sj.mp.4001863
  • [8] Hill MN, McEwen BS. Involvement of the endocannabinoid system in the neurobehavioural effects of stress and glucocorticoids. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(5):791-797. https://doi.org/10.1016/j.pnpbp.2009.11.001
  • [9] Salleh MR. Life event, stress and illness. Malays J Med Sci. 2008;15(4):9-18.
  • [10] Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res. 20023(4):865-871. https://doi.org/10.1016/S0022-3999(02)00429-4
  • [11] Prabhavathi RM, Prasad MP, Jayaramu M. Studies on qualitative and quantitative phytochemical analysis of Cissus quadrangularis. Adv Appl Sci Res. 2016;7(4):11-17.
  • [12] Markov DD, Novosadova EV. Chronic unpredictable mild stress model of depression: possible sources of poor reproducibility and latent variables. Biology. 2022;11(11):1621. https://doi.org/10.3390/biology11111621
  • [13] Strekalova T, Liu Y, Kiselev D, Khairuddin S, Chiu JL, Lam J, Chan YS, Pavlov D, Proshin A, Lesch KP, Anthony DC. Chronic mild stress paradigm as a rat model of depression: facts, artifacts, and future perspectives. Psychopharmacology. 2022;239(3):663-693. https://doi.org/10.1007/s00213-021-05982-w
  • [14] Sequeira-Cordero A, Salas-Bastos A, Fornaguera J, Brenes JC. Behavioural characterization of chronic unpredictable stress based on ethologically relevant paradigms in rats. Sci Rep. 2019;9(1):17403. https://doi.org/10.1038/s41598-019-53624-1
  • [15] Yadav P, Ganeshpurkar A, Sonkar N, Bansal D, Dubey N. Experimental studies on immunomodulatory potential of Cissus quadrangularis Linn. Niger J Exp Clin Biosci. 2014;2(1):49-53. https://doi.org/10.4103/2348-0149.135730.
  • [16] Chidambaram J, Venkatraman AC. Cissus quadrangularis stem alleviates insulin resistance, oxidative injury and fatty liver disease in rats fed high fat plus fructose diet. Food Chem Toxicol. 2010;48(8-9):2021-2029. https://doi.org/10.1016/j.fct.2010.04.044.
  • [17] Swamy AV, Kulkarni RV, Thippeswamy AH, Koti BC, Gore A. Evaluation of hepatoprotective activity of Cissus quadrangularis stem extract against isoniazid-induced liver damage in rats. Indian J Pharmacol. 2010;42(6):397-400. https://doi.org/10.4103/0253-7613.71920.
  • [18] Panthong A, Supraditaporn W, Kanjanapothi D, Taesotikul T, Reutrakul V. Analgesic, anti-inflammatory and venotonic effects of Cissus quadrangularis Linn. J Ethnopharmacol. 2007;110(2):264-270. https://doi.org/10.1016/j.jep.2006.09.018.
  • [19] Mosaib MG, Al Maruf MA, Islam R, Mahmud S, Nahid S, Sohana MA, Rony MH, Islam M, Zuhora FT, Islam S. Antibacterial activity of Cissus quadrangularis stem extract on the pathogenic and industrial waste watered bacteria. Eur J Med Health Sci. 2020;2(2):28-38. https://doi.org/10.34104/ejmhs.020.28038.
  • [20] Jain A, Dixit J, Prakash D. Modulatory effects of Cissus quadrangularis on periodontal regeneration by bovine-derived hydroxyapatite in intrabony defects: exploratory clinical trial. J Int Acad Periodontol. 2008;10(2):59-65.
  • [21] Jainu M, Mohan KV, Devi CS. Protective effect of Cissus quadrangularis on neutrophil mediated tissue injury induced by aspirin in rats. J Ethnopharmacol. 2006;104(3):302-305. https://doi.org/10.1016/j.jep.2005.08.076.
  • [22] Kothari SC, Shivarudraiah P, Venkataramaiah SB, Koppolu KP, Gavara S, Jairam R, Krishna S, Chandrappa RK, Soni MG. Safety assessment of C.quadrangularis extract (CQR-300): Subchronic toxicity and mutagenicity studies. Food Chem Toxicol. 2011;49(12):3343-3357. https://doi.org/10.1016/j.fct.2011.09.029
  • [23] Liu JI, Wang X, Shigenaga MK, Yeo HC, Mori A, Ames BN. Immobilization stress causes oxidative damage to lipid, protein, and DNA in the brain of rats. FASEB J. 1996;10(13):1532-1538.
  • [24] Olivenza R, Moro MA, Lizasoain I, Lorenzo P, Fernández AP, Rodrigo J, Boscá L, Leza JC. Chronic stress induces the expression of inducible nitric oxide synthase in rat brain cortex. J Neurochem. 2000;74(2):785-791. https://doi.org/10.1046/j.1471-4159.2000.740785.x.
  • [25] Tang Y, Zhong Z. Obtusifolin treatment improves hyperlipidemia and hyperglycemia: possible mechanism involving oxidative stress. Cell Biochem Biophys. 2014;70(3):1751-1757. https://doi.org/10.1007/s12013-014-0124-0
  • [26] Sahin E, Gümüşlü S. Immobilization stress in rat tissues: alterations in protein oxidation, lipid peroxidation and antioxidant defense system. Comp Biochem Physiol C Toxicol Pharmacol. 2007;144(4):342-347. https://doi.org/10.1016/j.cbpc.2006.10.009.
  • [27] Gupta V, Lahiri SS, Sultana S, Tulsawani RK, Kumar R. Anti-oxidative effect of Rhodiola imbricata root extract in rats during cold, hypoxia and restraint (C-H-R) exposure and post-stress recovery. Food Chem Toxicol. 2010;48(4):1019-1125. https://doi.org/10.1016/j.fct.2010.01.012.
  • [28] Qi B, Liu L, Zhang H, Zhou GX, Wang S, Duan XZ, Bai XY, Wang SM, Zhao DQ. Anti-fatigue effects of proteins isolated from Panax quinquefolium. J Ethnopharmacol. 2014;153(2):430-434. https://doi.org/10.1016/j.jep.2014.02.045.
  • [29] Xiao NN. Effects of resveratrol supplementation on oxidative damage and lipid peroxidation induced by strenuous exercise in rats. Biomol Ther (Seoul). 2015;23(4):374-378. https://doi.org/10.4062/biomolther.2015.015.
  • [30] Sureda A, Tauler P, Aguiló A, Cases N, Fuentespina E, Córdova A, Tur JA, Pons A. Relation between oxidative stress markers and antioxidant endogenous defences during exhaustive exercise. Free Radic Res. 2005;39(12):1317-1324. https://doi.org/10.1080/10715760500177500.
  • [31] Ji LL. Antioxidants and oxidative stress in exercise. Proc Soc Exp Biol Med. 1999;222(3):283-292. https://doi.org/10.1046/j.1525-1373.1999.d01-145.x.
  • [32] Peake J, Suzuki K. Neutrophil activation, antioxidant supplements and exercise-induced oxidative stress. Exerc Immunol Rev. 2004;10:129-141.
  • [33] Gökbel H. Acute exercise induced oxidative stress and antioxidant changes. Eur J Gen Med. 2006;3(3):126-131.
  • [34] Lin WT, Yang SC, Tsai SC, Huang CC, Lee NY. L-Arginine attenuates xanthine oxidase and myeloperoxidase activities in hearts of rats during exhaustive exercise. Br J Nutr. 2006;95(1):67-75. https://doi.org/10.1079/BJN20051602
  • [35] Ghadrdoost B, Vafaei AA, Rashidy-Pour A, Hajisoltani R, Bandegi AR, Motamedi F, Haghighi S, Sameni HR, Pahlvan S. Protective effects of saffron extract and its active constituent crocin against oxidative stress and spatial learning and memory deficits induced by chronic stress in rats. Eur J Pharmacol. 2011;667(1-3):222-229. https://doi.org/10.1016/j.ejphar.2011.05.012.
  • [36] Scrivo R, Vasile M, Bartosiewicz I, Valesini G. Inflammation as "common soil" of the multifactorial diseases. Autoimmun Rev. 2011;10(7):369-374. https://doi.org/10.1016/j.autrev.2010.12.006.
  • [37] Roshan S, Khan A, Tazneem B, Ali S. The effect of Echinacea angustifolia various biochemical parameters in stress induced rats. Pharmacologyonline. 2010; 2:542-550.
  • [38] Shaikh JR, Patil M. Qualitative tests for preliminary phytochemical screening: An overview. Int J Chem Stud. 2020;8(2):603-608. https://doi.org/10.22271/chemi.2020.v8.i2i.8834.
  • [39] Sastry GM, Adzhigirey M, Day T, Annabhimoju R, Sherman W. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J Comput Aided Mol Des. 2013;27(3):221-234. https://doi.org/10.1007/s10822-013-9644-8.
  • [40] Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455-461. https://doi.org/10.1002/jcc.21334.
  • [41] Allain CC, Poon LS, Chan CS, Richmond WF, Fu PC. Enzymatic determination of total serum cholesterol. Clin Chem. 1974;20(4):470-475. https://doi.org/10.1093/clinchem/20.4.470.
  • [42] Ortiz J, Fitizgerald LW, Lane S, Terwillinger R, Nestler EJ. Biochemical adaptations in the mesolimbic dopamine system in response to repeated stress. Neuropsychopharmacology. 1996; 14:443e52. https://doi.org/10.1016/0893-133X(95)00152-4
  • [43] Yilgor A, Demir C. Determination of oxidative stress level and some antioxidant activities in refractory epilepsy patients. Sci Rep. 2024;14(1):6688. https://doi.org/10.1038/s41598-024-57224-6
  • [44] Rahman I, Kode A, Biswas SK. Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat Protoc. 2006;1(6):3159-3165. https://doi.org/10.1038/nprot.2006.378
  • [45] Gündüz AM, Demir H, Toprak N, Akdeniz H, Demir C, Arslan A, Göya C. The effect of computed tomography on oxidative stress level and some antioxidant parameters. Acta Radiol. 2021;62(2):260-265. https://doi.org/10.1177/0284185120922
  • [46] Xiao Z, Yu X, Zhang S, Liang A. The Expression Levels and Significance of GSH, MDA, SOD, and 8‐OHdG in Osteochondral Defects of Rabbit Knee Joints. BioMed Res Int. 2022;2022(1):6916179. https://doi.org/10.1155/2022/6916179
  • [47] Khan A, Ali S. To study the effect of Allium sativum on various biochemical parameters on stress induced in albino rats. Res J Pharmacol Pharmacodyn. 2010;2(5):335-339.
  • [48] Khan A, Roshan S, Tazneem B, Ali S. Anti-ulcer effect of Argyreia speciosa ethanolic root extract in rats. Pharmacologyonline. 2010; 2: 389-394.
  • [49] Roshan S, Savadi RV. The effect of abutilon indicum on various biochemical parameters on stress induced in albino rats. Pharmacologyonline. 2010; 2: 266–274.
There are 49 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences (Other)
Journal Section Research Article
Authors

Mamoon H. Syed This is me 0000-0001-6627-7895

Ayesha Yasmeen This is me 0000-0002-2954-5413

Niraj Vyawahare This is me 0000-0001-6795-3314

Smeeta Sudir This is me 0000-0001-8682-303X

Tazneem Bachi 0000-0003-3220-2988

Sathish Kumar Mittapalli This is me 0000-0002-2028-2936

Mohammed Jaffer Sadik This is me 0000-0001-8175-1874

Ashok Kumar Uppuluru This is me 0000-0001-6777-3057

Racha Spanadana This is me 0009-0004-5059-3745

Roshan Safi This is me

Submission Date September 3, 2024
Acceptance Date December 29, 2024
Publication Date March 15, 2026
DOI https://doi.org/10.12991/jrespharm.1909318
IZ https://izlik.org/JA97ZU39CD
Published in Issue Year 2026 Volume: 30 Issue: 2

Cite

APA H. Syed, M., Yasmeen, A., Vyawahare, N., Sudir, S., Bachi, T., Mittapalli, S. K., Sadik, M. J., Uppuluru, A. K., Spanadana, R., & Safi, R. (2026). In silico and animal model study of Cissus quadrangularis stem ethanolic extract for unpredictable spontaneous stress. Journal of Research in Pharmacy, 30(2), 535-552. https://doi.org/10.12991/jrespharm.1909318
AMA 1.H. Syed M, Yasmeen A, Vyawahare N, et al. In silico and animal model study of Cissus quadrangularis stem ethanolic extract for unpredictable spontaneous stress. J. Res. Pharm. 2026;30(2):535-552. doi:10.12991/jrespharm.1909318
Chicago H. Syed, Mamoon, Ayesha Yasmeen, Niraj Vyawahare, et al. 2026. “In Silico and Animal Model Study of Cissus Quadrangularis Stem Ethanolic Extract for Unpredictable Spontaneous Stress”. Journal of Research in Pharmacy 30 (2): 535-52. https://doi.org/10.12991/jrespharm.1909318.
EndNote H. Syed M, Yasmeen A, Vyawahare N, Sudir S, Bachi T, Mittapalli SK, Sadik MJ, Uppuluru AK, Spanadana R, Safi R (March 1, 2026) In silico and animal model study of Cissus quadrangularis stem ethanolic extract for unpredictable spontaneous stress. Journal of Research in Pharmacy 30 2 535–552.
IEEE [1]M. H. Syed et al., “In silico and animal model study of Cissus quadrangularis stem ethanolic extract for unpredictable spontaneous stress”, J. Res. Pharm., vol. 30, no. 2, pp. 535–552, Mar. 2026, doi: 10.12991/jrespharm.1909318.
ISNAD H. Syed, Mamoon - Yasmeen, Ayesha - Vyawahare, Niraj - Sudir, Smeeta - Bachi, Tazneem - Mittapalli, Sathish Kumar - Sadik, Mohammed Jaffer - Uppuluru, Ashok Kumar - Spanadana, Racha - Safi, Roshan. “In Silico and Animal Model Study of Cissus Quadrangularis Stem Ethanolic Extract for Unpredictable Spontaneous Stress”. Journal of Research in Pharmacy 30/2 (March 1, 2026): 535-552. https://doi.org/10.12991/jrespharm.1909318.
JAMA 1.H. Syed M, Yasmeen A, Vyawahare N, Sudir S, Bachi T, Mittapalli SK, Sadik MJ, Uppuluru AK, Spanadana R, Safi R. In silico and animal model study of Cissus quadrangularis stem ethanolic extract for unpredictable spontaneous stress. J. Res. Pharm. 2026;30:535–552.
MLA H. Syed, Mamoon, et al. “In Silico and Animal Model Study of Cissus Quadrangularis Stem Ethanolic Extract for Unpredictable Spontaneous Stress”. Journal of Research in Pharmacy, vol. 30, no. 2, Mar. 2026, pp. 535-52, doi:10.12991/jrespharm.1909318.
Vancouver 1.Mamoon H. Syed, Ayesha Yasmeen, Niraj Vyawahare, Smeeta Sudir, Tazneem Bachi, Sathish Kumar Mittapalli, Mohammed Jaffer Sadik, Ashok Kumar Uppuluru, Racha Spanadana, Roshan Safi. In silico and animal model study of Cissus quadrangularis stem ethanolic extract for unpredictable spontaneous stress. J. Res. Pharm. 2026 Mar. 1;30(2):535-52. doi:10.12991/jrespharm.1909318