Asian Journal of Green Chemistry
3.8(Q2)
CiteScore
27
h-index

Green Phytochemical-Based Gastroprotection of Glucomannan against Indomethacin-Induced Gastric Ulcers via Cytoprotection and Anti-Apoptotic Effects

Articles in Press

Document Type : Original Research Article

Authors

Yuani Setiawati 1
Wibi Riawan 2
Jusak Nugraha 3
Mohammad Rais Mustafa 4
Sri Agus Sudjarwo 5
Wiwik Misaco Yuniarti 6
Rochmah Kurnijasanti 5

1 Doctoral Programme of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia

2 Department of Medical Biology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia

3 Department of Clinical Pathology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia

4 Department of Pharmacology, Faculty of Medicine, Malaya University, Kuala Lumpur, Malaysia

5 Department of Pharmacology, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia

6 Department of Clinical Science, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia

10.48309/ajgc.2026.564754.1884
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used but frequently induce gastric mucosal injury. Indomethacin disrupts mitochondrial function, promotes cytochrome c release, and activates caspase-3, leading to apoptosis and epithelial damage. Systemic inhibition of cyclooxygenase-1 (COX-1) further reduces prostaglandin synthesis, compromising gastric mucosal defense. Current anti-ulcer therapies show limited efficacy and notable adverse effects, highlighting the need for safer gastroprotective alternatives. Glucomannan, a plant-derived polysaccharide, has demonstrated the ability to enhance COX-1 expression and suppress apoptotic activity. This study aimed to evaluate the protective effects of Amorphophallus oncophyllus-derived glucomannan against indomethacin-induced gastric ulceration in Wistar rats and to elucidate its cytoprotective, and anti-apoptotic mechanisms. Thirty male Wistar rats were randomly allocated into five groups (n = 6). Group 1 received vehicle only; Group 2 was administered a single oral dose of indomethacin (50 mg/kg). Groups 3-5 were pretreated orally with glucomannan (40, 80, or 160 mg/kg) for seven consecutive days, followed by indomethacin administration. Macroscopic gastric lesions were quantified, and immunohistochemical analyses for COX-1 and caspase-3 expression were performed. Indomethacin induced marked gastric damage characterized by inflammation, erosion, ulceration, and hemorrhage. Glucomannan pretreatment significantly attenuated these lesions in a dose-dependent manner, with 160 mg/kg exhibiting the strongest protective effect (ulcer inhibition rate: 80%). Glucomannan restored COX-1 expression while markedly reducing caspase-3 activity, demonstrating enhanced mucosal cytoprotection and reduced apoptosis. Amorphophallus oncophyllus glucomannan confers potent gastroprotective effects against indomethacin-induced gastric injury, mediated through the upregulation of COX-1 and suppression of caspase-3-dependent apoptosis. These findings suggest its potential as a natural, safe prophylactic agent for NSAID-associated gastric ulceration.

Graphical Abstract

Green Phytochemical-Based Gastroprotection of Glucomannan against Indomethacin-Induced Gastric Ulcers via Cytoprotection and Anti-Apoptotic Effects

Keywords

Glucomannan
Indomethacin
COX-1
Caspase-3
Gastric ulcer

Subjects

©2026 The author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit: http://creativecommons.org/licenses/by/4.0/

PUBLISHER NOTE

Sami Publishing Company remains neutral concerning jurisdictional claims in published maps and institutional affiliations.

CURRENT PUBLISHER

Sami Publishing Company

[1] Jaiswal, F., Rai, A., Wal, P., Wal, A., Singh, S.P. Peptic ulcer: A review on etiology, pathogenesis and treatment. Asian Journal of Pharmaceutical Education and Research, 2021, 10(4), 1.
[2] Ghonge, P.G., Hatwar, P.R., Shelke, P.G., Bakal, R.L., Khandare, S.S. A comprehensive review on peptic ulcer disease: Types, pathophysiology, diagnosis and treatment. GSC Advanced Research and Reviews, 2025, 23(3), 26–35.
[3] Abbasi-Kangevari, M., Ahmadi, N., Fattahi, N., Rezaei, N., Malekpour, M.-R., Ghamari, S.-H., Moghaddam, S.S., Azadnajafabad, S., Esfahani, Z., Kolahi, A.A. Quality of care of peptic ulcer disease worldwide: A systematic analysis for the global burden of disease study 1990–2019. PLoS One, 2022, 17(8), e0271284.
[4] Altwejry, A.S., Alsaiari, O.A., Saleem, E.R., Alshanbri, N.K., Alzahrani, A.A., Alamri, S.M., Mahfouz, A.S.A.-D., Alghamdi, T.A., Asiri, F.M., Alzahrani, A.A. An overview on peptic ulcer disease, diagnosis and management approach. Pharmacophore, 2020, 11(2-2020), 123-126.
[5] Jafari, A., Andishfar, N., Esmaeilzadeh, Z., Khezri, M.R., Ghasemnejad‐Berenji, M. Gastroprotective effect of topiramate on indomethacin‐induced peptic ulcer in rats: Biochemical and histological analyses. Basic & Clinical Pharmacology & Toxicology, 2022, 130(5), 559-568.
[6] Küçükler, S., Kandemir, F.M., Yıldırım, S. Protective effect of chrysin on indomethacin induced gastric ulcer in rats: Role of multi-pathway regulation. Biotechnic & Histochemistry, 2022, 97(7), 490-503.
[7] Matsui, H., Shimokawa, O., Kaneko, T., Nagano, Y., Rai, K., Hyodo, I. The pathophysiology of non-steroidal anti-inflammatory drug (nsaid)-induced mucosal injuries in stomach and small intestine. Journal of Clinical Biochemistry and Nutrition, 2011, 48(2), 107-111.
[8] Almasaudi, S.B., Abbas, A.T., Al-Hindi, R.R., El-Shitany, N.A., Abdel-Dayem, U.A., Ali, S.S., Saleh, R.M., Al Jaouni, S.K., Kamal, M.A., Harakeh, S.M. Manuka honey exerts antioxidant and anti‐inflammatory activities that promote healing of acetic acid‐induced gastric ulcer in rats. Evidence‐Based Complementary and Alternative Medicine, 2017, 2017(1), 5413917.
[9] Wang, X.Y., Yin, J.Y., Hu, J.L., Nie, S.P., Xie, M.Y. Gastroprotective polysaccharide from natural sources: Review on structure, mechanism, and structure–activity relationship. Food Frontiers, 2022, 3(4), 560-591.
[10] Kapoor, D.U., Sharma, H., Maheshwari, R., Pareek, A., Gaur, M., Prajapati, B.G., Castro, G.R., Thanawuth, K., Suttiruengwong, S., Sriamornsak, P. Konjac glucomannan: A comprehensive review of its extraction, health benefits, and pharmaceutical applications. Carbohydrate Polymers, 2024, 339, 122266.
[11] Parente, J.P., Adao, C.R., da Silva, B.P., Tinoco, L.W. Structural characterization of an acetylated glucomannan with antiinflammatory activity and gastroprotective property from cyrtopodium andersonii. Carbohydrate Research, 2014, 391, 16-21.
[12] Du, Q., Liu, J., Ding, Y. Recent progress in biological activities and health benefits of konjac glucomannan and its derivatives. Bioactive Carbohydrates and Dietary Fibre, 2021, 26, 100270.
[13] Aanisah, N., Wardhana, Y.W., Chaerunisa, A.Y. Modifications and pharmaceutical applications of glucomannan as novel pharmaceutical excipient in indonesia. Journal of Pharmaceutical Sciences, 2022, 2, 190.
[14] Anggela, A., Setyaningsih, W., Wichienchot, S., Harmayani, E. Oligo-glucomannan production from porang (amorphophallus oncophyllus) glucomannan by enzymatic hydrolisis using β-mannanase. Indonesian Food and Nutrition Progress, 2021, 17(1), 23-27.
[15] Suyoko, E., Pandiangan, D., Valery, T.M., Nainggolan, N., Artha, E.N., Putri, G.N.V. The effectiveness of Porang (Amorphophallus oncophyllus) powder solution on healing inflammation of the stomach of Wistar rats (Rattus norvegicus) induced with acetic acid. International Journal of Science and Research, 2022, 11(8), 465–472.
[16] Zhao, Y., Jayachandran, M., Xu, B. In vivo antioxidant and anti-inflammatory effects of soluble dietary fiber konjac glucomannan in type-2 diabetic rats. International Journal of Biological Macromolecules, 2020, 159, 1186-1196.
[17] Chen, X.Y., Chen, H.M., Liu, Y.H., Zhang, Z.B., Zheng, Y.F., Su, Z.Q., Zhang, X., Xie, J.H., Liang, Y.Z., Fu, L.D. The gastroprotective effect of pogostone from pogostemonis herba against indomethacin-induced gastric ulcer in rats. Experimental biology and medicine, 2016, 241(2), 193-204.
[18] El-Ashmawy, N.E., Khedr, E.G., El-Bahrawy, H.A., Selim, H.M. Gastroprotective effect of garlic in indomethacin induced gastric ulcer in rats. Nutrition, 2016, 32(7-8), 849-854.
[19] Hafez, H., Morsy, M., Mohamed, M., Zenhom, N. Mechanisms underlying gastroprotective effect of paeonol against indomethacin-induced ulcer in rats. Human & Experimental Toxicology, 2019, 38(5), 510-518.
[20] Xu, C., Ding, C., Zhou, N., Ruan, X.M., Guo, B.X. A polysaccharide from aloe vera l. Var. Chinensis (haw.) berger prevents damage to human gastric epithelial cells in vitro and to rat gastric mucosa in vivo. Journal of Functional Foods, 2016, 24, 501-512.
[21] Drini, M. Peptic ulcer disease and non-steroidal anti-inflammatory drugs. Australian Prescriber, 2017, 40(3), 91.
[22] Ko, K.A., Lee, D.K. Nonsteroidal anti-inflammatory drug-induced peptic ulcer disease. The Korean Journal of Helicobacter and Upper Gastrointestinal Research, 2025, 25(1), 34.
[23] Rajagopal, H.M., Manjegowda, S.B., Serkad, C., Dharmesh, S.M. A modified pectic polysaccharide from turmeric (curcuma longa) with antiulcer effects via anti–secretary, mucoprotective and il–10 mediated anti–inflammatory mechanisms. International Journal of Biological Macromolecules, 2018, 118, 864-880.
[24] Keshk, W.A., Zahran, S.M., Katary, M.A., Ali, D.A.E. Modulatory effect of silymarin on nuclear factor-erythroid-2-related factor 2 regulated redox status, nuclear factor-κb mediated inflammation and apoptosis in experimental gastric ulcer. Chemico-Biological Interactions, 2017, 273, 266-272.
[25] Liu, J., Fang, J., Zhang, J., Wang, D., Zhang, Z., Wang, C., Sun, J., Chen, J., Li, H., Jing, S. Protective effect of anwulignan on gastric injury induced by indomethacin in mice. The Journal of Pharmacology and Experimental Therapeutics, 2022, 383(1), 80-90.
Asian Journal of Green Chemistry

Articles in Press, Accepted Manuscript
Available Online from 29 January 2026

  • Receive Date 07 November 2025
  • Revise Date 24 December 2025
  • Accept Date 21 January 2026

Home

A-Z Journals

SPC Publisher's Policies

Indexing and Abstracting

Editorial Board

Guide for Authors

Submit Manuscript

Contact Us

Using and Citation