Lupeol: A Triterpenoid Isolated from the Stem Bark of Hymenocardia Acida (tul.) Exhibits a van der Waal Antagonism on the Alpha Subunit of Gastric H+K+Atpase – A Promising Antiulcer Principle

Abstract

Background Hymenocardia acida (HA) is one of the numerous medicinal plants in Nigeria with ethnomedicinal history of usage in the treatment of ulcer. The study aimed at isolating antiulcer principle(s) from the stem bark of HA as well as the mechanism of action determination.

Methods Antiulcer screenings of the crude extract, aqueous fraction, and bulked VLC fractions were performed using in vivo and in vitro models. Docking was carried out by using PyRx.

Results Crude extract (HA; 1 mg/mL) and the aqueous fraction of H. acida (HAA; 1 mg/mL) showed an acid neutralizing capacity (MEq) of 0.3948 and 0.4035, respectively which is significantly different from 0.431 MEq showed by negative control (distilled water) at p<0.05. BVLC 3 (1 mg/mL) showed a significant value of 0.4049 MEq. However, HA showed a dose-dependent decrease in activity across doses examined, with 100 mg/kg showing an ulcer index of 10.00±2.89 (61.50%) and cimetidine (positive control; 100 mg/kg), also showed the highest ulcer index of 3.67±0.88 (85.9%), which is significantly different from ulcer index of 26.00±6.35 (0.00%) p<0.05 observed in the negative control (5% dimethylsulphoxide). The highest ulcer index of 8.00±1.32 (65.10%) was noted in BVLC 3. Bioactive BVLC 3, resulted in an isolated compound (BF3B2A). The compound was suggested to be lupeol, with a docking score of −7.7. It showed a van der Waal interaction with some key amino acid residues in the vonoprazan binding site.

Conclusion The experimental studies justify the ethnomedicinal claim of usage among locals.

Key words

Acid neutralizing capacity - Docking - Hymenocardia acida - Lupeol - Ulcer

Publication History

Received: 01 March 2023

Accepted: 06 June 2023

Article published online:
25 August 2023

• References

• 1 Ndububa D, Adeyemi O. Peptic Ulcer Disease in Nigeria. J Obafemi Awolowo Univ Med Student’s Assoc 2008; 14 DOI: 10.4314/ifemed.v14i1.41737.
• 2 Ogunma Benjamin G, Oluwasegun Adekanmi A, Ogochukwu U. et al. Antiulcer and toxicological evaluation of bi-herbal mixture of Emilia coccinea and Occimum gratissimum on Wistar rats. ~ 3648 ~ J Pharmacogn Phytochem 2019; 8
• 3 Kavitt RT, Lipowska AM, Anyane-Yeboa A. Ian Gralnek. Diagnosis and Treatment of Peptic Ulcer Disease. Am J Med 2019; 132
• 4 Boyko TV, Longaker MT, Yang GP. Review of the Current Management of Pressure Ulcers. Adv Wound Care 2018; 7: 57-67 DOI: 10.1089/wound.2016.0697.
• 5 Miklós BG. Helicobacter pylori – 2021. Orv Hetil 2021; 162 DOI: 10.1556/650.2021.32181.
• 6 Alfahad M, Jasim MHM, Qazzaz ME. et al. Proton pump inhibitors and peptic ulcer management: Antioxidant mechanisms. J Drug Deliv Ther 2021; 11 DOI: 10.22270/jddt.v11i4-s.4955.
• 7 Alfahad M, Jasim MHM, Qazzaz ME. et al. Proton pump inhibitors and peptic ulcer management: Antioxidant mechanisms. J Drug Deliv Ther 2021; 11: 242-246 DOI: 10.22270/jddt.v11i4-s.4955.
• 8 Abe K, Tani K, Fujiyoshi Y. Conformational rearrangement of gastric H+,K+-ATPase induced by an acid suppressant. Nat Commun 2011; 2 DOI: 10.1038/ncomms1154.
• 9 Shin JM, Munson K, Vagin O. et al. The gastric HK-ATPase: Structure, function, and inhibition. Pflugers Arch Eur J Physiol 2009; 457: 609-622
• 10 Alfahad M, Jasim MHM, Qazzaz ME. et al. Proton pump inhibitors and peptic ulcer management: Antioxidant mechanisms. J Drug Deliv Ther 2021; 11: 242-246 DOI: 10.22270/jddt.v11i4-s.4955.
• 11 Abe K, Irie K, Nakanishi H. et al. Crystal structures of the gastric proton pump. Nature 2018; 556: 214-229 DOI: 10.1038/s41586-018-0003-8.
• 12 Usman AM, Danjuma NM, Ya’u J. et al. Antidiarrhoeal potentials of methanol bark extract of Hymenocardia Acida Tul (Euphorbiaceae) in laboratory animals. Bull Natl Res Cent 2021; 45 DOI: 10.1186/s42269-021-00575-1.
• 13 Amom T-AT, Yahwe R, Vershima J. Phytochemical and Medicinal activities of Hymenocardia acida Tul (Euphorbiaceae): A Review. 2013
• 14 John O, Alexander GI. Friedelanone and other triterpenoids from Hymenocardia acida. 2008
• 15 Sofidiya M, Lange C, Sattler I. Bioactivity profile of compounds isolated from Hymenocardia acida Tul. leaves. Planta Med 2010; 76 DOI: 10.1055/s-0030-1264439.
• 16 Onen P, Ocira D, Omara T. et al. Preliminary Phytochemical Screening of Plumbago zeylanica L. Roots and Its Aphrodisiac Effect in Male Rats. Asian J Appl Chem Res 2021; DOI: 10.9734/ajacr/2021/v8i330193.
• 17 Boya D, Ahmed J. Comparison of acid-neutralizing capacity of antacids in Erbil City. Zanco J Med Sci 2021; 25 DOI: 10.15218/zjms.2021.023.
• 18 Devhare LD, Gokhale N. Acid neutralizing capacity and antimicrobial potential of selected solvent extract from various indigenous plants. J Adv Sci Res 2021; 12 DOI: 10.55218/jasr.202112423.
• 19 Kumar V, Verma P, Kaur A. et al. In-vitro antiulcer activities of petal extract of Crocus sativus var. cashmerianus. J Med Bot 2020; DOI: 10.25081/jmb.2020.v4.6225.
• 20 Zahid R, Asif HM, Faisal R. et al. In vitro and in vivo anti-Helicobacter pylori activity of selected medicinal plants employed for the management of gastrointestinal disorders. Pak J Pharm Sci 2020; 33: 2809-2814
• 21 Palacios-espinosa JF, Núñez-aragón PN, Gomez-chang E. et al. Anti‐helicobacter pylori activity of Artemisia ludoviciana subsp. Mexicana and two of its bioactive components, estafiatin and eupatilin. Molecules 2021; 26 DOI: 10.3390/molecules26123654.
• 22 Adinortey MB, Ansah C, Galyuon I. et al. In Vivo Models Used for Evaluation of Potential Antigastroduodenal Ulcer Agents. Ulcers 2013; 2013 DOI: 10.1155/2013/796405.
• 23 Ofusori AE, Moodley R, Jonnalagadda SB. Antiulcerogenic effects of Celosia trigyna plant extracts on ethanol-induced gastric ulcer in adult Wistar rats. J Tradit Complement Med 2020; 10 DOI: 10.1016/j.jtcme.2019.11.004.
• 24 Umre R, Ganeshpurkar A, Ganeshpurkar A. et al. In vitro, in vivo and in silico antiulcer activity of ferulic acid. Futur J Pharm Sci 2018; 4: 248-253
• 25 Associate Professor RC. SwissADME predictions of pharmacokinetics and drug-likeness properties of small molecules present in Ipomoea mauritiana Jacq. ~ 2063 ~ J Pharmacogn. Phytochem 2019; 8
• 26 Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017; 7 DOI: 10.1038/srep42717.
• 27 Ahmed MH, Momoh MK. Determination Of the Effectiveness and Acid Neutralization Capacities ( ANC ) Of Some Commercial Antacid Tablets 2021; 5: 335-344
• 28 Bijekar S. Ethanomedicinal properties of euphorbiaceae family-A comprehensive review Antimicrobial and Phytochemicals studies of some Euphorbiaceae members View project. 2014
• 29 Venkata C, Prakash S, Prakash I. Isolation and Structural Characterization of Lupane Triterpenes from Polypodium vulgare. 2012
• 30 Igoli OJ, Alexander GI. Friedelanone and other triterpenoids from Hymenocardia acida . Int J Phys Sci 2008; 3
• 31 Jain PS, Bari SB. Isolation of lupeol, stigmasterol and campesterol from petroleum ether extract of woody stem of Wrightia tinctoria . Asian J Plant Sci 2010; 9 DOI: 10.3923/ajps.2010.163.167.
• 32 Silva ATME, Magalhães LP, Wagner da Nova M. et al. Lupeol and its esters: Nmr, powder xrd data and in vitro evaluation of cancer cell growth. Brazilian J Pharm Sci 2017; 53 DOI: 10.1590/S2175-97902017000300251.
• 33 Li L, Liang HQ, Liao SX. et al. Chemical studies of Strobilanthes cusia . Yao Xue Xue Bao 1993; 28
• 34 Malinowska M, Miroslaw B, Sikora E. et al. New lupeol esters as active substances in the treatment of skin damage. PLoS One 2019; 14 DOI: 10.1371/journal.pone.0214216.
• 35 Malinowska M, Sikora E, Ogonowski J. Lipophilicity of lupeol semisynthetic derivates. Pr Nauk Uniw Ekon we Wrocławiu 2015; DOI: 10.15611/pn.2015.411.08.
• 36 Mvondo JGM, Matondo A, Mawete DT. et al. In Silico ADME/T Properties of Quinine Derivatives using SwissADME and pkCSM Webservers. Int J Trop Dis Heal 2021; DOI: 10.9734/ijtdh/2021/v42i1130492.
• 37 Sohag AAM, Hossain MT, Rahaman MA. et al. Molecular pharmacology and therapeutic advances of the pentacyclic triterpene lupeol. Phytomedicine 2022; 99