Home Antidiarrheal activity of Bridelia ferruginea bark methanolic extract involves modulation ATPases in mice and inhibition of muscarinic acetylcholine receptor (M3) and prostaglandin E2 receptor 3 (EP3) in silico
Article
Licensed
Unlicensed Requires Authentication

Antidiarrheal activity of Bridelia ferruginea bark methanolic extract involves modulation ATPases in mice and inhibition of muscarinic acetylcholine receptor (M3) and prostaglandin E2 receptor 3 (EP3) in silico

  • Blessing Olugbamila Omolaso , Julius Kolawole Adesanwo , Ahmed Adebayo Ishola , Adeoti Gbemisola Adegoke , Francis O. Akingbule , Yetunde Ayoka Ipadeola and Kayode Ezekiel Adewole ORCID logo EMAIL logo
Published/Copyright: November 3, 2021
Journal of Complementary and Integrative Medicine
From the journal Journal of Complementary and Integrative Medicine Volume 20 Issue 4

Abstract

Objectives

Diarrhea, an abnormal state in which the individual has about three or more daily bowel movements, is now considered one of the most challenging global public health problems. Using plant products, such as Bridelia ferruginea is an alternative treatment option. The objective of this study was to investigate the antidiarrheal activity of B. ferruginea bark methanolic extract (BfME) and the mechanisms involved.

Methods

BfME antidiarrheal activity was evaluated in mice model of castor oil-induced diarrhea and enteropooling. To evaluate motility, gastrointestinal transit time was carried out using phenol red meal, while intestinal activities of selected ATPases were also evaluated. Furthermore, the active components in BfME were detected by GC-MS analysis, while molecular docking of the most abundant compounds with muscarinic acetylcholine receptor (M3) and prostaglandin E2 receptor 3 (EP3) were conducted.

Results

BfME at 400 and 800 mg/kg showed antidiarrheal activity by delaying onset of diarrhea, reduced gastrointestinal transit and increased intestinal activities of Na+ K+-ATPase, Ca2+ Mg2+-ATPase and Mg2+-ATPase. Molecular docking revealed that γ-sitosterol, α-amyrin, and stigmasterol have outstanding binding affinity for M3 and EP3.

Conclusions

In view of these results, the observed antidiarrheal activity possibly occurs via the activation of ATPases activities and inhibition of M3 and EP3.

Keywords: Bridelia ferruginea ; castor oil; diarrhea; gastrointestinal transit; mice
Corresponding author: Kayode Ezekiel Adewole, Department of Biochemistry, Faculty of Basic Medical Sciences, University of Medical Sciences, Ondo City, Ondo State, Nigeria, E-mail:

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: This study involves no human subject.

  5. Ethical approval: The local Institutional Review Board approved the study.

References

1. da Costa, DS, dos S Negreiros, P, da Silva, VG, Nunes, DB, Acha, BT, Quintans-Junior, LJ, et al.. Antidiarrheal activity of farnesol in rodents: pharmacological actions and molecular docking. Eur J Pharmacol 2020;874:172986. https://doi.org/10.1016/j.ejphar.2020.172986.Search in Google Scholar PubMed

2. Awe, EO, Kolawole, SO, Wakeel, KO, Abiodun, OO. Antidiarrheal activity of Pyrenacantha staudtii engl. (iccacinaceae) aqueous leaf extract in rodents. J Ethnopharmacol 2011;137:148–53. https://doi.org/10.1016/j.jep.2011.04.068.Search in Google Scholar PubMed

3. Kelly, P. Infectious diarrhoea. Medicine (Baltim) 2015;43:235–8. https://doi.org/10.1016/j.mpmed.2015.02.005.Search in Google Scholar

4. World Health Organisation. Prevention and control of cholera outbreaks: WHO policy and recommendations-case management. Geneva: WHO; 2016.Search in Google Scholar

5. Araújo, T, Douglas, SC, Nayara, AS, Luan, KM, Simone, A, Ana, PO, et al.. Antidiarrheal activity of cashew gum, a complex heteropolysaccharide extracted from exudate of Anacardium occidentale L. in rodents. J Ethnopharmacol 2015;174:299–307. https://doi.org/10.1016/j.jep.2015.08.020.Search in Google Scholar PubMed

6. Khan, RA. Natural remedy for increasing sperm count: an approach towards tropical. J Pakistan Med Assoc 2020;70:372–3. https://doi.org/10.5455/JPMA.23269.Search in Google Scholar PubMed

7. Tadesse, E, Engidawork, E, Nedi, T, Mengistu, G. Evaluation of the anti-diarrheal activity of the aqueous stem extract of Lantana camara Linn (Verbenaceae) in mice. BMC Compl Alternative Med 2017;17:1–8. https://doi.org/10.1186/s12906-017-1696-1.Search in Google Scholar PubMed PubMed Central

8. Zhang, J, Wang, S, Li, Y, Xu, P, Chen, F, Tan, Y, et al.. Anti-diarrheal constituents of Alpinia oxyphylla. Fitoterapia 2013;89:149–56. https://doi.org/10.1016/j.fitote.2013.04.001.Search in Google Scholar PubMed

9. Omolaso, BO, Oluwole, FS, Odukanmi, OA, Julius, K, Ishola, AA, Adewole, KE. Evaluation of the gastrointestinal anti-motility effect of Anacardium occidentale stem bark extract: a mechanistic study of antidiarrheal activity. J Pharm Anal 2020. https://doi.org/10.1016/j.jpha.2020.06.009.Search in Google Scholar PubMed PubMed Central

10. Ferraz, CR, Silva, DB, Carolina, L, Armando, H, Canabrava, N, Bispo-da-silva, LB, et al.. Antidiarrhoeic effect and dereplication of the aqueous extract of Annona crassiflora (Annonaceae). Nat Prod Res 2017;33:563–7. https://doi.org/10.1080/14786419.2017.1396589.Search in Google Scholar PubMed

11. Ekanem, J, Kolawole, O, Abbah, O. Trypanocidal potential of methanolic extracts of Bridelia ferruginea benth bark in Rattus novergicus. Afr J Biochem Res 2008;2:45–50.Search in Google Scholar

12. Olajide, OA, Aderogba, MA, Okorji, UP, Fiebich, BL. Bridelia ferruginea produces antineuroinflammatory activity through inhibition of Nuclear Factor-kappa B and p38 MAPK signalling. Evid base Compl Alternative Med 2012;2012:1–8. https://doi.org/10.1155/2012/546873.Search in Google Scholar PubMed PubMed Central

13. Ajiboye, TO, Abdussalam, FA, Adeleye, AO, Iliasu, GA, Ariyo, FA. Bridelia ferruginea promotes reactive oxygen species detoxification in N-nitrosodiethylamine-treated rats. J Diet Suppl 2013;10:210–28. https://doi.org/10.3109/19390211.2013.822451.Search in Google Scholar PubMed

14. Irobi, O, Moo-Young, M, Anderson, W, Daramola, S. Antimicrobial activity of bark extract of Bridelia ferruginea (Euphorbiaceae). J Ethnopharmacol 1994;43:185–90. https://doi.org/10.1016/0378-8741(94)90041-8.Search in Google Scholar PubMed

15. Cimanga, K, Ying, L, De Bruyne, T, Apers, S, Cos, P, Hermans, N, et al.. Radical scavenging and xanthine oxidase inhibitory activity of phenolic compounds from Bridelia ferruginea stem bark. J Pharm Pharmacol 2001;53:757–61. https://doi.org/10.1211/0022357011775893.Search in Google Scholar PubMed

16. Olarewaju, O, Oloyede, O, Ojo, O, Onikanni, A, Ajiboye, B, State, E. In-vitro antioxidant activities of the stem bark extract fractions of Bridelia ferruginea. J Biol Agric Healthc 2014;4:1–7.Search in Google Scholar

17. Oyebode, O, Erukainure, OL, Zuma, L, Collins, U, Koorbanally, NA, Islam, S, et al.. In vitro and computational studies of the antioxidant and anti-diabetic properties of Bridelia ferruginea in vitro and computational studies of the antioxidant and anti-diabetic. J Biomol Struct Dyn 2020. https://doi.org/10.1080/07391102.2020.1852961.Search in Google Scholar PubMed

18. Kareem, K, Kareem, S, Adeyemo, O, Egberongbe, R. In vitro antimicrobial properties of Bridelia ferruginea on some clinical isolates. Agric Biol J N Am 2010;1:416–20. https://doi.org/10.5251/abjna.2010.1.3.416.420.Search in Google Scholar

19. Kolawole, O, Adesoye, A. Evaluation of the antimalarial activity of Bridelia ferruginea benth bark. Burn Br Columbia SENRA Acad Publ 2010;4:1039–44.Search in Google Scholar

20. Olajide, OA, Makinde, JM, Okpako, DT, Awe, SO. Studies on the anti-inflammatory and related pharmacological properties of the aqueous extract of Bridelia ferruginea stem bark. J Ethnopharmacol 2000;71:153–60. https://doi.org/10.1016/s0378-8741(99)00201-9.Search in Google Scholar PubMed

21. Yi, H, Zhang, L, Gan, Z, Xiong, H, Yu, C, Du, H, et al.. High therapeutic efficacy of Cathelicidin-WA against postweaning diarrhea via inhibiting inflammation and enhancing epithelial barrier in the intestine. Sci Rep 2016;6:1–12. https://doi.org/10.1038/srep25679.Search in Google Scholar PubMed PubMed Central

22. Barmeyer, C, Harren, M, Schmitz, H, Heinzel-Pleines, U, Mankertz, J, Seidler, U, et al.. Mechanisms of diarrhea in the interleukin-2-deficient mouse model of colonic inflammation. Am J Physiol Gastrointest Liver Physiol 2004;286:244–52. https://doi.org/10.1152/ajpgi.00141.2003.Search in Google Scholar PubMed

23. Afolayan, M, Srivedavyasasri, R, Asekun, OT, Oluwole, B, Ross, SA, Science, S, et al.. Chemical and biological studies on Bridelia ferruginea grown in Nigeria. Nat Prod Res 2019;33:287–91. https://doi.org/10.1080/14786419.2018.1440225.Search in Google Scholar PubMed PubMed Central

24. Mostafa, M, Nahar, N, Mosihuzzaman, M, Sokeng, S, Fatima, N, Atta-ur-Rahman, et al.. Phosphodiesterase-I inhibitor quinovic acid glycosides from Bridelian dellensis. Nat Prod Res 2006;20:686–92. https://doi.org/10.1080/14786410600661658.Search in Google Scholar PubMed

25. Pettit, GR, Searcy, JD, Tan, R, Cragg, GM, Melody, N, Knight, JC, et al.. Antineoplastic agents. 585. Isolation of Bridelia ferruginea anticancer podophyllotoxins and synthesis of 4-Aza-podophyllotoxin structural modifications. J Nat Prod 2016;79:507–18. https://doi.org/10.1021/acs.jnatprod.5b00873.Search in Google Scholar PubMed

26. Bruyne, T, Cimanga, K, Pieters, L, Claeys, M, Dommisse, R, Vlietinck, A. Gallocatechin – (4′→0→7)-epigallocatechin, a new biflavonoid isolated from BrideliaFerruginea. Nat Prod Lett 1997;11:47–52. https://doi.org/10.1080/10575639708043756.Search in Google Scholar

27. Das, J, Hadi, Y, Salam, R, Hoda, M, Lassi, Z, Bhutta, Z. Fly control to prevent diarrhoea in children. Cochrane Database Syst Rev 2018;12:CD011654. https://doi.org/10.1002/14651858.CD011654.pub2.Search in Google Scholar PubMed PubMed Central

28. Ye, X, Tai, W, Zhao, Q, Xu, DP, Zhang, X, Jie, C, et al.. The influence of porcine epidemic diarrhea virus on pig small intestine mucosal epithelial cell function. Arch Virol 2019;164:83–90. https://doi.org/10.1007/s00705-018-4061-x.Search in Google Scholar PubMed PubMed Central

29. Rose, A, Valdes, RJ. Understanding the sodium pump and its relevance to disease. Clin Chem 1994;40:1674–85. https://doi.org/10.1093/clinchem/40.9.1674.Search in Google Scholar

30. Chauhan, N, Lee, J, Siegel, G. Na+-K+-ATPase mRNA levels and plaque load in Alzheimer’s disease. J Mol Neurosci 1997;9:151–6. https://doi.org/10.1007/bf02800498.Search in Google Scholar

31. Beeler, T, Wang, T, Gable, K, Lee, S. Comparison of the rat microsomal Mg-ATPase of various tissues. Arch Biochem Biophys 1985;243:644–54. https://doi.org/10.1016/0003-9861(85)90542-9.Search in Google Scholar PubMed

32. Veklich, T, Kosterin, S. Comparative study of the properties of Na+, K+-ATPase and Mg2+-ATPase of the myometrium plasma membrane. Ukr Biokhim Zh 2005;77:66–75.Search in Google Scholar

33. Gums, J. Magnesium in cardiovascular and other disorders. Am J Health Syst Pharm 2004;61:1569–76. https://doi.org/10.1093/ajhp/61.15.1569.Search in Google Scholar PubMed

34. Grover, M, Camilleri, M. Ramosetron in irritable bowel syndrome with diarrhea: new hope or the same old story? Clin Gastroenterol Hepatol 2014;12:960–2. https://doi.org/10.1016/j.cgh.2013.12.025.Search in Google Scholar PubMed PubMed Central

35. Kobayashi, S, Ikeda, K, Suzuki, M, Yamada, T, Miyata, K. Effects of YM905, a novel muscarinic M3-receptor antagonist, on experimental models of bowel dysfunction in vivo. Jpn J Pharmacol 2001;86:281–8. https://doi.org/10.1254/jjp.86.281.Search in Google Scholar PubMed

36. Aleem, A. Dual mechanisms of anti-muscarinic and Ca++ antagonistic activities to validate the folkloric uses of Cyperus niveus Retz . as antispasmodic and antidiarrheal. J Ethnopharmacol 2018;213:138–48. https://doi.org/10.1016/j.jep.2017.11.006.Search in Google Scholar PubMed

37. Boby, N, Abbas, MA, Lee, E, Im, Z, Hsu, WH, Park, S. Protective effect of Pyrus ussuriensis Maxim. extract against ethanol-induced gastritis in rats. Antioxidants 2021;10:439.10.3390/antiox10030439Search in Google Scholar

38. Fujii, S, Suzuki, K, Kawamoto, A, Ishibashi, F, Nakata, T. PGE 2 is a direct and robust mediator of anion/fluid secretion by human intestinal epithelial cells. Sci Rep 2016;6:1–15. https://doi.org/10.1038/srep36795.Search in Google Scholar PubMed PubMed Central

39. Garber, JC, Barbee, RW, Bielitzki, JT, Clayton, LA, Donovan, JC. Guide for the care and use of laboratory animals. NIH; 1985.Search in Google Scholar

40. Doherty, S. Inhibition of arachinodic acid release as the mechanism by which glucocorticoids inhibit endotoxin‐ induced diarrhoea. Br J Pharmacol 1981;73:549–54. https://doi.org/10.1111/j.1476-5381.1981.tb10454.x.Search in Google Scholar PubMed PubMed Central

41. Ronner, P, Gazzotti, P, Carafoli, E. A lipid requirement for the (Ca2+ + Mg2+)-activated ATPase of erythrocyte membranes. Arch Biochem Biophys 1977;179:578–83. https://doi.org/10.1016/0003-9861(77)90146-1.Search in Google Scholar PubMed

42. Bewaji, CO, Olorunsogo, OO, Bababunmi, EA. Comparison of the membrane-bound (Ca2+ + Mg2+)-ATPase in erythrocyte ghosts from some mammalian species. Comp Biochem Physiol B Comp Biochem 1985;82:117–22. https://doi.org/10.1016/0305-0491(85)90138-5.Search in Google Scholar PubMed

43. Liu, H, Hofmann, J, Fish, I, Schaake, B, Eitel, K, Bartuschat, A, et al.. Structure-guided development of selective M3 muscarinic acetylcholine receptor antagonists. Proc Natl Acad Sci U S A 2018;115:12046–50. https://doi.org/10.1073/pnas.1813988115.Search in Google Scholar PubMed PubMed Central

44. Audet, M, White, KL, Breton, B, Zarzycka, B, Han, GW, Lu, Y, et al.. Crystal structure of misoprostol bound to the labor inducer prostaglandin E 2 receptor. Nat Chem Biol 2019;15:11–7. https://doi.org/10.1038/s41589-018-0160-y.Search in Google Scholar PubMed PubMed Central

45. 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;31:455–61. https://doi.org/10.1002/jcc.21334.Search in Google Scholar PubMed PubMed Central

46. Shaf, M, Khan, R, Ahmed, M. Phytochemical assessment of Iphiona aucheri (Bioss.) Anderb. and its cytotoxic, antioxidant and antidiabetic activities. Bangladesh J Bot 2020;49:913–8.10.3329/bjb.v49i4.52497Search in Google Scholar

47. Parmar, KM, Bhagwat, DS, Sinha, SK, Katare, NT. The potency of eriosematin E from Eriosema chinense Vogel . against enteropathogenic Escherichia coli induced diarrhoea using preclinical and molecular docking studies. Acta Trop 2019;193:84–91. https://doi.org/10.1016/j.actatropica.2019.02.025.Search in Google Scholar PubMed

48. Rawat, P, Singh, PK, Kumar, V. Evidence based traditional anti-diarrheal medicinal plants and their phytocompounds. Biomed Pharmacother 2017;96:1453–64. https://doi.org/10.1016/j.biopha.2017.11.147.Search in Google Scholar PubMed

49. Tagne, MAF, Kamgang, R, Noubissi, PA, Oyono, J-LE. Activity of Oxalis barrelieri aqueous extract on rat secretory diarrhea and intestine transit. J Appl Pharmaceut Sci 2015;5:58–62.Search in Google Scholar

50. Tadesse, WT, Hailu, AE, Gurmu, AE, Mechesso, AF. Experimental assessment of antidiarrheal and antisecretory activity of 80% methanolic leaf extract of Zehneria scabra in mice. BMC Compl Alternative Med 2014;13:460–8. https://doi.org/10.1186/1472-6882-14-460.Search in Google Scholar PubMed PubMed Central

51. Verma, N, Singh, AP, Gupta, A, Sahu, PK, Rao, CV. Antidiarrheal potential of standardized extract of Rhododendron arboreum Smith flowers in experimental animals. Indian J Pharmacol 2011;43:689–94. https://doi.org/10.4103/0253-7613.89827.Search in Google Scholar PubMed PubMed Central

52. Otshudi, AL, Vercruysse, A, Foriers, A. Contribution to the ethnobotanical, phytochemical and pharmacological studies of traditionally used medicinal plants in the treatment of dysentery and diarrhoea in Lomela area, Democratic Republic of Congo (DRC). J Ethnopharmacol 2000;71:411–23. https://doi.org/10.1016/s0378-8741(00)00167-7.Search in Google Scholar PubMed

Received: 2021-06-04
Accepted: 2021-10-21
Published Online: 2021-11-03

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Plants with potential anti-ulcerogenic activity and possible mechanism of actions based on their phyto-constitutional profile
  4. Ayurvedic medicine for the treatment of chronic rhinosinusitis: a systematic review of randomized and non-randomized trials
  5. The roles of HDAC with IMPDH and mTOR with JAK as future targets in the treatment of rheumatoid arthritis with combination therapy
  6. Research Articles
  7. Alterations in expression of α1-adrenergic receptors possibly are involved in prevention of age-associated apoptosis in rat hippocampus by treadmill exercise
  8. A solid lipid particle formulation of long pepper extract reduces pain and astrocyte activation in a rat model of neuropathic pain
  9. Modulation of glucose metabolism-related genes in diabetic rats treated with herbal synthetic anti-diabetic compound (α-HSA): insights from transcriptomic profiling
  10. Gastroprotective and ulcer healing effects of Nauclea pobeguinii (Rubiaceae) on experimentally induced gastric ulcers in male Wistar rats
  11. Blood pressure lowering effects of Vernonia amygdalina Del. Aqueous fraction on hypertensive Wistar Kyoto rats
  12. Oleaster oil (Olea europaea sylvestris) effects on the efficiency of the reproductive system of diet-induced obese male Wistar rats
  13. Antidiarrheal activity of Bridelia ferruginea bark methanolic extract involves modulation ATPases in mice and inhibition of muscarinic acetylcholine receptor (M3) and prostaglandin E2 receptor 3 (EP3) in silico
  14. Optimization of total phenolic content, total flavonoid content and anti-gout properties of polyherbal formulation
  15. Fast improvements in functional status after osteopathic manipulative treatment based on myofascial release in patients with moderate or severe fibromyalgia: a retrospective study
  16. Causes of adverse outcomes in acute intestinal obstruction
  17. Scopoletin a potential phytochemical therapy for antitubercular treatment drug induced liver injury (ATT-DILI) model in Wistar rats
  18. Non-monotonic dose-response of di-(2-ethylhexyl) phthalate isolated from Penicillium citrinum XT6 on adipogenesis and expression of PPARγ and GLUT4 in 3T3-L1 adipocytes
https://doi.org/10.1515/jcim-2021-0240
Keywords for this article
Bridelia ferruginea; castor oil; diarrhea; gastrointestinal transit; mice

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Plants with potential anti-ulcerogenic activity and possible mechanism of actions based on their phyto-constitutional profile
  4. Ayurvedic medicine for the treatment of chronic rhinosinusitis: a systematic review of randomized and non-randomized trials
  5. The roles of HDAC with IMPDH and mTOR with JAK as future targets in the treatment of rheumatoid arthritis with combination therapy
  6. Research Articles
  7. Alterations in expression of α1-adrenergic receptors possibly are involved in prevention of age-associated apoptosis in rat hippocampus by treadmill exercise
  8. A solid lipid particle formulation of long pepper extract reduces pain and astrocyte activation in a rat model of neuropathic pain
  9. Modulation of glucose metabolism-related genes in diabetic rats treated with herbal synthetic anti-diabetic compound (α-HSA): insights from transcriptomic profiling
  10. Gastroprotective and ulcer healing effects of Nauclea pobeguinii (Rubiaceae) on experimentally induced gastric ulcers in male Wistar rats
  11. Blood pressure lowering effects of Vernonia amygdalina Del. Aqueous fraction on hypertensive Wistar Kyoto rats
  12. Oleaster oil (Olea europaea sylvestris) effects on the efficiency of the reproductive system of diet-induced obese male Wistar rats
  13. Antidiarrheal activity of Bridelia ferruginea bark methanolic extract involves modulation ATPases in mice and inhibition of muscarinic acetylcholine receptor (M3) and prostaglandin E2 receptor 3 (EP3) in silico
  14. Optimization of total phenolic content, total flavonoid content and anti-gout properties of polyherbal formulation
  15. Fast improvements in functional status after osteopathic manipulative treatment based on myofascial release in patients with moderate or severe fibromyalgia: a retrospective study
  16. Causes of adverse outcomes in acute intestinal obstruction
  17. Scopoletin a potential phytochemical therapy for antitubercular treatment drug induced liver injury (ATT-DILI) model in Wistar rats
  18. Non-monotonic dose-response of di-(2-ethylhexyl) phthalate isolated from Penicillium citrinum XT6 on adipogenesis and expression of PPARγ and GLUT4 in 3T3-L1 adipocytes
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 31.10.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jcim-2021-0240/pdf
Scroll to top button