Phytochemical screening, psychopharmacological and memory-cognitive potentiality of the Stephania japonica methanolic extract: In vivo and in silico approaches

Year 2026, Volume: 30 Issue: 1 , 275 - 295 , 11.01.2026

Maitry Das , Md. Mamun Or Rashid , Md. Monirul Islam , Md. Siam Hossain , Md. Monir Hossain Md. Nazmul Hasan Zilani , Mohammad Salim Hossain

https://doi.org/10.12991/jrespharm.1657514

https://izlik.org/JA44MZ49WE

Abstract

Stephania japonica is a traditional medicinal plant, possesses many pharmacological activities which are reported already; however, the neuropharmacological efficacy is still unclear. Considering this, our study was designed to investigate the neurobehavioral, spatial learning-memory, and motor learning efficacies of the methanolic extract of S. japonica (MSJ) on mice. Phytochemical screening was performed through GC-MS analysis. Anxiolytic efficacy of MSJ was investigated through open field, hole cross, elevated plus maze, and hole board tests separately; whereas antidepressant efficacy was assessed using forced swim and tail suspension tests. Spatial learning and memory, and motor learning efficacies of the mice were investigated through Morris water maze test (MWMT) and single palate reaching task (SPRT) respectively. A dose-dependent significant anxiolytic and antidepressant efficacies (p<0.05) were found in MSJ-treated group. In MWMT, spending time increased significantly for the MSJ-treated mice compared to control (p<0.05). Besides, in SPRT, the average success rate brought on by ingesting of MSJ increased approx. 1.5 folds (p<0.05) compared to control, which resembles improvement of the positive neurocognitive effects in mice. In-silico modeling predicted that 3 bioactive compounds out of 18 (found from GC-MS analysis) exhibit favorable ADMET profiles and good docking scores with targeted receptors of AMPA, GABA, and NMDA; hence may responsible for the in-vivo effects. Based on the above results, it might be said that MSJ possess substantial anxiolytic-antidepressant, visuospatial learning, and motor skill-learning efficacies. Further studies are recommended to conduct the in-vivo neurological investigations and reveal the mechanisms of each phytoconstituents separately for the drug development program

Keywords

Neuropharmacology , Stephania japonica , GC-MS , Molecular docking

References

• [1] Burton KJ, Allen S. A review of neurological disorders presenting at a paediatric neurology clinic and response to anticonvulsant therapy in Gambian children. Ann Trop Paediatr. 2003; 23(2): 139-143. https://doi.org/10.1179/027249303235002215
• [2] Zelnik N, Pacht A, Obeid R, Lerner A. Range of neurologic disorders in patients with celiac disease. Pediatrics. 2004; 113(6): 1672-1676. https://doi.org/10.1542/peds.113.6.1672 , [3] Uddin MS, Al Mamun A, Asaduzzaman M, Hosn F, Abu Sufian M, Takeda S, Herrera-Calderon O, Abdel-Daim MM, Uddin GMS, Noor MAA, Begum MM, Kabir MT, Zaman S, Sarwar MS, Rahman MM, Rafe MR, Hossain MF, Hossain MS, Ashraful Iqbal M, Sujan MAR. Spectrum of Disease and Prescription Pattern for Outpatients with Neurological Disorders: An Empirical Pilot Study in Bangladesh. Ann Neurosci. 2018; 25(1): 25-37. https://doi.org/10.1159/000481812
• [4] Dhawan K, Dhawan S, Chhabra S. Attenuation of benzodiazepine dependence in mice by a tri-substituted benzoflavone moiety of Passiflora incarnata Linneaus: a non-habit forming anxiolytic. J Pharm Pharm Sci. 2003; 6(2): 215-222.
• [5] Halim MA, Rashid MM, Mazid MA, Uddın A, Hossain MS, Rashıd MM. Central nervous system depressant, gastrointestinal motility, and brine shrimp lethality bioassay of the methanolic extract of Suaeda maritima in mice model. J Res Pharm. 2022; 26(6): 1868-1876. https://doi.org/10.29228/jrp.276
• [6] Moniruzzaman M, Hossain MS, Bhattacharjee PS. Evaluation of antinociceptive activity of methanolic extract of leaves of Stephania japonica Linn. J Ethnopharmacol. 2016; 186: 205-208. https://doi.org/10.1016/j.jep.2016.04.008
• [7] Ghani A. Medicinal plants of Bangladesh with chemical constituents and uses. Asiatic society of Bangladesh, Bangladesh; 2003.
• [8] Jahan R, Khatun A, Nahar N, Jahan FI, Chowdhury AR, Nahar A, Seraj S, Mahal MJ, Khatun Z, Rahmatullah M. Use of Menispermaceae family plants in folk medicine of Bangladesh. Adv Nat Appl Sci. 2010; 4(1): 1-9.
• [9] Zehad A, Islam GJ, Rashid M, Juthy NJ, Zannah S. Antidiabetic and antihyperlipidemic activities of methanolic leaf extract of Stephania japonica in alloxan ınduced diabetic rats. Pharmacol Pharm. 2017; 8(04):109. https://doi.org/10.4236/pp.2017.84008
• [10] Islam MD, Akter SF, Islam MA, Uddin MS. Exploration of antidiabetic activity of Stephania japonica leaf extract in alloxan-ınduced swiss albino diabetic mice. J Pharm Res Int. 2019; 26(6): 1-12. https://doi.org/10.9734/jpri/2019/v26i630154
• [11] Al-Amin MY, Lahiry A, Ferdous R, Hasan MK, Kader MA, Alam AK, Saud ZA, Sadik MG. Stephania japonica ameliorates scopolamine-ınduced memory ımpairment in mice through ınhibition of acetylcholinesterase and oxidative stress. Adv Pharmacol Pharm Sci. 2022; 2022: 8305271. https://doi.org/10.1155/2022/8305271
• [12] Rahman MH, Alam MB, Chowdhury NS, Jha MK, Hasan M, Khan MM, Rahman MS, Haque ME. Antioxidant, analgesic and toxic potentiality of Stephania japonica (Thunb.) Miers. leaf. Int J Pharmacol. 2011; 7(2): 257–262. https://doi.org/10.3923/ijp.2011.257.262
• [13] Raji RO, Muhammad HL, Abubakar A, Maikai SS, Raji HF. Acute and sub-acute toxicity profile of crude extract and fractions of Gymnema sylvestre. Clin Phytosci. 2021; 7(1):56. https://doi.org/10.1186/s40816-021-00290-4
• [14] Islam NU, Khan I, Rauf A, Muhammad N, Shahid M, Shah MR. Antinociceptive, muscle relaxant and sedative activities of gold nanoparticles generated by methanolic extract of Euphorbia milii. BMC Complement Altern Med. 2015; 15: 160. https://doi.org/10.1186/s12906-015-0691-7
• [15] Moniruzzaman M, Atikur Rahman M, Ferdous A. Evaluation of sedative and hypnotic activity of ethanolic extract of Scoparia dulcis Linn. Evid Based Complement Alternat Med. 2015; 2015: 873954. https://doi.org/10.1155/2015/873954
• [16] Kumar K, Sharma S, Kumar P, Deshmukh R. Therapeutic potential of GABA(B) receptor ligands in drug addiction, anxiety, depression and other CNS disorders. Pharmacol Biochem Behav. 2013; 110: 174-184. https://doi.org/10.1016/j.pbb.2013.07.003
• [17] Takeda H, Tsuji M, Matsumiya T. Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. Eur J Pharmacol. 1998; 350(1): 21-29. https://doi.org/10.1016/s0014-2999(98)00223-4
• [18] Shahed-Al-Mahmud M, Lina SM. Evaluation of sedative and anxiolytic activities of methanol extract of leaves of Persicaria hydropiper in mice. Clin Phytosci. 2017; 3: 20. https://doi.org/10.1186/s40816-017-0056-5
• [19] Das AK, Molla S, Sykat MR, Ali A, Haque T, Rahman L, Babu I, Islam MH, Islam MT. Phytochemical and pharmacological review on Stephania japonica. Int J Pharma Sci Res. 2019; 14(1): 10433-10436. https://doi.org/10.26717/BJSTR.2019.14.002500
• [20] Johnston GA. GABA(A) receptor channel pharmacology. Curr Pharm Des. 2005; 11(15): 1867-1885. https://doi.org/10.2174/1381612054021024
• [21] Hanrahan JR, Chebib M, Johnston GA. Flavonoid modulation of GABA(A) receptors. Br J Pharmacol. 2011; 163(2): 234-245. https://doi.org/10.1111/j.1476-5381.2011.01228.x
• [22] Costa JP, de Oliveira GA, de Almeida AA, Islam MT, de Sousa DP, de Freitas RM. Anxiolytic-like effects of phytol: possible involvement of GABAergic transmission. Brain Res. 2014; 1547: 34-42. https://doi.org/10.1016/j.brainres.2013.12.003
• [23] Abdelhalim A, Karim N, Chebib M, Aburjai T, Khan I, Johnston GA, Hanrahan J. Antidepressant, Anxiolytic and antinociceptive activities of constituents from Rosmarinus Officinalis. J Pharm Pharm Sci. 2015; 18(4): 448-459. https://doi.org/10.18433/j3pw38
• [24] Möhler H. The GABA system in anxiety and depression and its therapeutic potential. Neuropharmacology. 2012; 62(1): 42-53. https://doi.org/10.1016/j.neuropharm.2011.08.040
• [25] Hoang THX, Ho DV, Van Phan K, Le QV, Raal A, Nguyen HT. Effects of Hippeastrum reticulatum on memory, spatial learning and object recognition in a scopolamine-induced animal model of Alzheimer's disease. Pharm Biol. 2020; 58(1): 1098-1104. https://doi.org/10.1080/13880209.2020.1841810
• [26] Bennett JC, McRae PA, Levy LJ, Frick KM. Long-term continuous, but not daily, environmental enrichment reduces spatial memory decline in aged male mice. Neurobiol Learn Mem. 2006; 85(2): 139-152. https://doi.org/10.1016/j.nlm.2005.09.003
• [27] Altayyar M, Nasser JA, Thomopoulos D, Bruneau M Jr. The implication of physiological ketosis on the cognitive brain: A narrative review. Nutrients. 2022; 14(3): 513. https://doi.org/10.3390/nu14030513
• [28] Murray AJ, Knight NS, Cole MA, Cochlin LE, Carter E, Tchabanenko K, Pichulik T, Gulston MK, Atherton HJ, Schroeder MA, Deacon RM. Novel ketone diet enhances physical and cognitive performance. FASEB J. 2016; 30(12):4021. https://doi.org/10.1096/fj.201600773R
• [29] Chen CC, Gilmore A, Zuo Y. Study motor skill learning by single-pellet reaching tasks in mice. J Vis Exp. 2014; (85): 51238. https://doi.org/10.3791/51238
• [30] Sheibani V, Mandegary A, Vazifekhahan E, Kasbzade Z, Asadi A, Sharififar F. Zataria multiflora Boiss. extract improves spatial memory and learning capacity in scopolamine-induced amnesic rats. Avicenna J Phytomed. 2019; 9(6): 587-596. https://doi.org/10.22038/ajp.2019.13540
• [31] Meng XY, Zhang HX, Mezei M, Cui M. Molecular docking: a powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des. 2011; 7(2): 146-157. https://doi.org/10.2174/157340911795677602
• [32] Roth RH, Cudmore RH, Tan HL, Hong I, Zhang Y, Huganir RL. Cortical synaptic AMPA receptor plasticity during motor learning. Neuron. 2020; 105(5): 895-908. https://doi.org/10.1016/j.neuron.2019.12.005 [33] Hasan MT, Hernández-González S, Dogbevia G, Treviño M, Bertocchi I, Gruart A, Delgado-García JM. Role of motor cortex NMDA receptors in learning-dependent synaptic plasticity of behaving mice. Nat Commun. 2013; 4: 2258. https://doi.org/10.1038/ncomms3258
• [34] Zilani MNH, Islam MA, Biswas P, Anisuzzman M, Hossain H, Shilpi JA, Hasan MN, Hossain MG. Metabolite profiling, anti-inflammatory, analgesic potentials of edible herb Colocasia gigantea and molecular docking study against COX-II enzyme. J Ethnopharmacol. 2021; 281: 114577. https://doi.org/10.1016/j.jep.2021.114577
• [35] Wangusi BM, Kanja LW, Ole-Mapenay IM, Onyancha JM. Acute toxicity, phytochemical screening, analgesic, and anti-ınflammatory activities of aqueous and methanol root extracts of Maerua triphylla A. Rich. (Capparaceae). Evid Based Complement Alternat Med. 2021; 2021: 3121785. https://doi.org/10.1155/2021/3121785
• [36] Apu A, Muhit M, Tareq S, Pathan A, Jamaluddin A, Ahmed M. Antimicrobial activity and brine shrimp lethality bioassay of the leaves extract of Dillenia indica Linn. J Young Pharm. 2010; 2(1) :50-53. https://doi.org/10.4103/0975-1483.62213 [37] Rashid MM, Hussain MS, Rashid MM, Halim MA, Sen N, Millat MS, Sarker MA. In vivo analgesic potential in swiss albino mice and in vitro thrombolytic and membrane stabilizing activities of methanolic extract from Suaeda maritima whole plant. Bagcilar Med Bull. 2017; 2(1): 13-18. https://doi.org/10.5350/BMB20170306094829
• [38] Somani RR, Kadam G, Vohra R, Vijayaraghavan S, Shirodkar PY. Studies of CNS activities of some mannich bases of 1, 3, 4-oxadiazole. Int J Pharmacol. 2010; 6(5): 696-704.
• [39] Porsolt RD, Anton G, Blavet N, Jalfre M. Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol. 1978; 47(4): 379-391. https://doi.org/10.1016/0014-2999(78)90118-8
• [40] Amin KR, Uddin MG, Rashid MM, Sharmin T. New insight in neuropharmacological activities of Dioscorea alata. Discov Phytomed. 2018; 5(1): 1-6. https://doi.org/10.15562/phytomedicine.2018.52
• [41] Can A, Dao DT, Terrillion CE, Piantadosi SC, Bhat S, Gould TD. The tail suspension test. J Vis Exp. 2012; 59: e3769. https://doi.org/10.3791/3769
• [42] Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl). 1985; 85(3): 367-370. https://doi.org/10.1007/bf00428203
• [43] Kitanaka J, Kitanaka N, Hall FS, Fujii M, Goto A, Kanda Y, Koizumi A, Kuroiwa H, Mibayashi S, Muranishi Y, Otaki S, Sumikawa M, Tanaka K, Nishiyama N, Uhl GR, Takemura M. Memory impairment and reduced exploratory behavior in mice after administration of systemic morphine. J Exp Neurosci. 2015; 9: 27-35. https://doi.org/10.4137/jen.s25057
• [44] Tran YH, Nguyen TT, Nguyen PT, Nguyen KT, Duong CX, Tran HM. Effects of Ganoderma lucidum extract on morphine-induced addiction and memory impairment in mice. Biointerface Res Appl Chem. 2021; 12(1): 1076 - 1084. https://doi.org/10.33263/BRIAC121.10761084
• [45] Otu UG, Atiang BJ, Etah N, Patrick UO, Effiong OO. Ethanolic extract of Gongronema latifolium improves learning and memory in Swiss albino Mice. J Drug Deliv Ther. 2022; 12(1): 45. https://doi.org/10.22270/jddt.v12i1.5276
• [46] Hossain MS, Seddique AB, Sharmin S, Rashid MMO, Islam A, Hossain MM. Nigella sativa oil ımproves motor skill learning of albino mice: In Vivo and ın silico ınvestigations. Evid Based Complement Alternat Med. 2023; 2023: 8498066. https://doi.org/10.1155/2023/8498066
• [47] Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem. 1998; 19(14): 1639-1662. https://doi.org/10.1002/(SICI)1096-987X(19981115)19:14%3C1639::AID-JCC10%3E3.0.CO;2-B