THE EFFECT OF BITTER MELON FRUIT EXTRACT (MOMORDICA CHARANTIA L.) SUPPLEMENTED WITH SNAKEHEAD FISH POWDER (CHANNA STRIATA) ON CLINICAL IMPROVEMENT OF DIABETIC ULCERS: A RANDOMIZED CONTROLLED TRIAL

FAHRUN NUR ROSYID; MUHTADI; ANDI SUHENDI; SH SUGIHARTO; DWI LINNA SUSWARDANY; DWI ROSELLA KOMALA SARI; AHMAD FADHLUR RAHMAN

doi:10.22159/ijap.2025.v17s2.17

Authors

FAHRUN NUR ROSYID Department of Medical Surgical Nursing, School of Nursing, Universitas Muhammadiyah Surakarta, Surakarta-57169, Central Java, Indonesia
MUHTADI Faculty of Pharmacy, Universitas Muhammadiyah Surakarta, Surakarta-57169, Central Java, Indonesia
ANDI SUHENDI Faculty of Pharmacy, Universitas Muhammadiyah Surakarta, Surakarta-57169, Central Java, Indonesia
SH SUGIHARTO Department of Medical Surgical Nursing, School of Nursing, Universitas Muhammadiyah Surakarta, Surakarta-57169, Central Java, Indonesia
DWI LINNA SUSWARDANY Department of Public Health, University of Muhammadiyah Surakarta, Surakarta-57169, Central Java, Indonesia
DWI ROSELLA KOMALA SARI Department of Physiotherapy, Universitas Muhammadiyah Surakarta, Surakarta-57169, Central Java, Indonesia
AHMAD FADHLUR RAHMAN School of Nursing, Faculty of Health Science, Universitas Muhammadiyah Surakarta, Surakarta-57169, Central Java, Indonesia https://orcid.org/0000-0002-3107-3435

DOI:

https://doi.org/10.22159/ijap.2025.v17s2.17

Keywords:

Bitter melons, Momordica charantia L., Channa striata, Ulcer clinical improvement, Diabetic foot ulcer

Abstract

Objective: This study aims to examine supplementation of a combination of bitter melon extract with snakehead fish powder for clinical improvement of diabetic foot ulcers (DFU).

Methods: This study used a randomized, double-blinded, placebo-controlled trial. A total of 50 DFU patients who met the criteria were divided into 2 groups, namely: 25 patients as the treatment group were given supplementation of bitter melon extract combination with snakehead fish powder and a control group of 50 patients who received a placebo. This intervention was carried out for 4 w. DFU clinical improvement was measured with perfusion, extent, depth, infection, sensation (PEDIS) scores at baseline, weeks 2, 3, and 4. Data were analyzed using a generalized linear model (GLM) and post hoc.

Results: After 4 w of treatment, the PEDIS score of the treatment group in week 1 decreased in week 2 (6.48±1.19), significantly (p = 0.003), decreased in week 3 (5.64±1.18) and significantly (p = 0.0001), decreased in week 4 (4.28±1.06) and was significant (p = 0.0001), while the control group in week 1 decreased in week 2 (5.68±2.30), but not significant (p=0.574), decreased for week 3 (5.52±2.23), but not significant (p=0.161), decreased for week 4 (5.28±2.13) and not significant (p=0.056), and there was an effect of supplementation with a combination of bitter melon extract and snakehead fish powder on the PEDIS score (p=0.004).

Conclusion: Supplementation of a combination of bitter melon extract with snakehead fish powder significantly reduced PEDIS Score on DFU patient and has an effect on clinical improvement.

References

Yan F, Zhao L, Quan X, Zhu J. Association between stress hyperglycemia ratio and diabetes mellitus mortality in American adults: a retrospective cohort study and predictive model establishment based on machine learning algorithms (NHANES 2009-2018). Diabetol Metab Syndr. 2024;16(1):79. doi: 10.1186/s13098-024-01324-w, PMID 38566220.

Wijayanti E, Samsuria IK, Widyaningrum D. Lipid profile and soluble E-selectin levels differences between type 2 diabetes mellitus overweight obese and under norm weight patients. Biomedika. 2022;14(2):147-57. doi: 10.23917/biomedika.v14i2.18629.

Jomova K, Raptova R, Alomar SY, Alwasel SH, Nepovimova E, Kuca K. Reactive oxygen species toxicity oxidative stress and antioxidants: chronic diseases and aging. Arch Toxicol. 2023;97(10):2499-574. doi: 10.1007/s00204-023-03562-9, PMID 37597078.

Rosyid FN, Prasetyo TA, Prabawati CY, Supratman, Sugiarto, HS KH. The effect of bitter melon (Momordica charantia L.) leaves extractonon glycated albumin in diabetic foot ulcers: randomized controlled trial. Bangladesh J Med Sci. 2021;20(2):281-7. doi: 10.3329/bjms.v20i2.51536.

Jiao YR, Chen KX, Tang X, Tang YL, Yang HL, Yin YL. Exosomes derived from mesenchymal stem cells in diabetes and diabetic complications. Cell Death Dis. 2024;15(4):271. doi: 10.1038/s41419-024-06659-w, PMID 38632264.

Rahayuningsih N, Pratiwi AL, Pebiansyah A. Cost effectiveness analysis of antibiotic usage in diabetic foot ulcus patients in dokter soekardjo tasikmalaya hospital. Int J App Pharm. 2022;14(5):123-6. doi: 10.22159/ijap.2022.v14s5.25.

Rosyid F. Wounds: physiological mechanisms and factors affecting healing. Int J Res Med Sci. 2022;10(4):1001. doi: 10.18203/2320-6012.ijrms20221000.

Cioce A, Cavani A, Cattani C, Scopelliti F. Role of the skin immune system in wound healing. Cells. 2024;13(7):624. doi: 10.3390/cells13070624, PMID 38607063.

Lyttle BD, Vaughn AE, Bardill JR, Apte A, Gallagher LT, Zgheib C. Effects of microRNAs on angiogenesis in diabetic wounds. Front Med (Lausanne). 2023 Mar 20;10:1140979. doi: 10.3389/fmed.2023.1140979, PMID 37020673.

Suh JW, Lee KM, KO EA, Yoon DS, Park KH, Kim HS. Promoting angiogenesis and diabetic wound healing through delivery of protein transduction domain BMP2 formulated nanoparticles with hydrogel. J Tissue Eng. 2023 Jan;14:20417314231190641. doi: 10.1177/20417314231190641, PMID 37601810.

Smith J, Rai V. Novel factors regulating proliferation migration and differentiation of fibroblasts keratinocytes and vascular smooth muscle cells during wound healing. Biomedicines. 2024;12(9):1939. doi: 10.3390/biomedicines12091939, PMID 39335453.

Choudhary V, Choudhary M, Bollag WB. Exploring skin wound healing models and the impact of natural lipids on the healing process. Int J Mol Sci. 2024 Mar;25(7):3790. doi: 10.3390/ijms25073790, PMID 38612601.

Everts PA, Lana JF, Onishi K, Buford D, Peng J, Mahmood A. Angiogenesis and tissue repair depend on platelet dosing and bioformulation strategies following orthobiological platelet rich plasma procedures: a narrative review. Biomedicines. 2023;11(7):1922. doi: 10.3390/biomedicines11071922, PMID 37509560.

Oguntibeju OO. Medicinal plants and their effects on diabetic wound healing. Vet World. 2019 May;12(5):653-63. doi: 10.14202/vetworld.2019.653-663, PMID 31327900.

Albahri G, Badran A, Hijazi A, Daou A, Baydoun E, Nasser M. The therapeutic wound healing bioactivities of various medicinal plants. Life (Basel Switzerland). 2023 Jan;13(2):317. doi: 10.3390/life13020317, PMID 36836674.

Hussain A, Fatima H, Komal M, Kauser S, Yaqub S, Akram S. Evaluation of peel flesh and seeds of bitter gourd (Momordica charantia L.) for biologically active components through development of powders and ethanolic extracts. Discov Appl Sci. 2024;6(8):432. doi: 10.1007/s42452-024-06086-8.

LG, W, AMP, DR, RM, Gamolo. Nutraceuticals and bioactive components of bitter gourd (Momordica charantia). Int J Biol Sci. 2024;25(5):167-75. doi: 10.12692/ijb/25.5.167-175.

Gayathry KS, John JA. A comprehensive review on bitter gourd (Momordica charantia L.) as a gold mine of functional bioactive components for therapeutic foods. Food Prod Process and Nutr. 2022;4(1):10. doi: 10.1186/s43014-022-00089-x.

Jiratchariyakul W, Wiwat C, Vongsakul M, Somanabandhu A, Leelamanit W, Fujii I. HIV inhibitor from thai bitter gourd. Planta Med. 2001 Jul;67(4):350-3. doi: 10.1055/s-2001-14323, PMID 11458453.

Rosyid FN, Muhtadi M, Hudiyawati D, Sugiyarti S, Rahman AF. Improving diabetic foot ulcer healing with adjuvant bitter melon leaf extract (Momordica charantia L.). Open Access Maced J Med Sci. 2022;10(T8):122-6. doi: 10.3889/oamjms.2022.9503.

Salami MS, Bahrami G, Arkan E, Izadi Z, Miraghaee S, Samadian H. Co-electrospun nanofibrous mats loaded with bitter gourd (Momordica charantia) extract as the wound dressing materials: in vitro and in vivo study. BMC Complement Med Ther. 2021;21(1):111. doi: 10.1186/s12906-021-03284-4, PMID 33827547.

Sagastegui Guarniz WA, Silva Correa CR, Torre VE, Gonzalez Blas MV, Sagastegui Guarniz WO, Calderon Pena AA. Wound healing by topical application of Momordica charantia L. formulations on mice. Vet World. 2021 Oct;14(10):2699-704. doi: 10.14202/vetworld.2021.2699-2704, PMID 34903928.

Cicek SS. Momordica charantia L. Diabetes related bioactivities quality control and safety considerations. Front Pharmacol. 2022 May 17;13:904643. doi: 10.3389/fphar.2022.904643, PMID 35656300.

Arsih RB, Taurina W, Andrie M. Characterization of snakehead fish (Channa striata) meat simplicia as raw material for wound healing drugs. J Vet. 2022 Sep;23(3):401-8. doi: 10.19087/jveteriner.2022.23.3.401.

Kwan SH, Abdul Aziz NHKA, Ismail MN. Bioactive proteins in Channa striata promote wound healing through angiogenesis and cell proliferation. Protein Pept Lett. 2020;27(1):48-59. doi: 10.2174/0929866526666190730121711, PMID 31362651.

Tran Thi Ngoc Bich, Doan Quang Tri, Chen Yi Ching, Huynh Dang Khoa. Productivity and economic viability of snakehead channa striata culture using an aquaponics approach. Aquacultural Engineering. 2020 May;89:102057. doi: 10.1016/j.aquaeng.2020.102057.

Apriasari ML, Puspitasari D, Utami JP. Anti-inflammatory effect of channa micropeltes extract in angiogenesis of diabetes mellitus wound healing. Review of Diabetic Studies. 2022;18(4):166-70. doi: 10.1900/RDS.2022.18.166.

Laoli D, Waruwu E, Telaumbanua BV, Zebua RD, Nazara RV. Productivity of snakehead fish (Channa striata) as a source of wound healing. AJOAS. 2023 Aug;6(2):288-92. doi: 10.31258/ajoas.6.2.288-292.

AA, HG, Syafruddin Ilyas, Olivia Avriyanti Hanafiah. The effect of snakehead fish (Channa striata) extract on dry socket wound healing: TGF-β1 expression in rats model. Biosci Med J Biomed Transl Res. 2024;8(7):4639-47. doi: 10.37275/bsm.v8i7.1035.

Taslim NA, Fitriana N, Suprapti NL, Marsella CP, Bukhari A, Rasyid H. Effects of channa striata extract on albumin serum and neutrophil-to-lymphocyte ratio in hyperglycemic rats with wound injury: a randomized control study. Open Access Maced J Med Sci. 2022;10(A):450-5. doi: 10.3889/oamjms.2022.8179.

Lee VL, Choo BK, Norazit A, Noor SM, Shaikh MF. Channa striatus in inflammatory conditions: a systematic review. Front Pharmacol. 2022 Dec 5;13:1076143. doi: 10.3389/fphar.2022.1076143, PMID 36545318.

Akyuz E, Turkoglu S, Sozgen Başkan K, Tutem E, Apak MR. Comparison of antioxidant capacities and antioxidant components of commercial bitter melon (Momordica charantia L.) products. Turk J Chem. 2020;44(6):1663-73. doi: 10.3906/kim-2007-67, PMID 33488261.

Bortolotti M, Mercatelli D, Polito L. Momordica charantia a nutraceutical approach for inflammatory-related diseases. Front Pharmacol. 2019 May 8;10:486. doi: 10.3389/fphar.2019.00486, PMID 31139079.

Basch E, Gabardi S, Ulbricht C. Bitter melon (Momordica charantia): a review of efficacy and safety. Am J Health Syst Pharm. 2003 Feb;60(4):356-9. doi: 10.1093/ajhp/60.4.356, PMID 12625217.

Saeed F, Afzaal M, Niaz B, Arshad MU, Tufail T, Hussain MB. Bitter melon (Momordica charantia): a natural healthy vegetable. Int J Food Prop. 2018;21(1):1270-90. doi: 10.1080/10942912.2018.1446023.

Gurlek Kisacik O, Gunes U, Yaprakci MV, Altunbas K. Effectiveness of bitter melon extract in the treatment of ischemic wounds in rats. Turk J Biol. 2018;42(6):506-16. doi: 10.3906/biy-1804-36, PMID 30983870.

Akbulut S, Pekcan M. The effects of topical applications of momordica charantia extract on wound healing on full floor excisional skin wound and diabetic wounds. Fabad J Pharm Sci. 2024;49(2):423-34. doi: 10.55262/fabadeczacilik.1349346.

Zamanifard M, Nasiri M, Yarahmadi F, Zonoori S, Razani O, Salajegheh Z. Healing of diabetic foot ulcer with topical and oral administrations of herbal products: a systematic review and meta-analysis of randomized controlled trials. Int Wound J. 2024;21(2):e14760. doi: 10.1111/iwj.14760, PMID 38356150.

Sharma S, Sharma MC, Kohli DV. Wound healing activity of the ether chloroform extract of Momordica charantia fruits s in rats. Dig J Nanomater Biostructures. 2010;5(1):123-6.

Singh R, Garcia Gomez I, Gudehithlu KP, Singh AK. Bitter melon extract promotes granulation tissue growth and angiogenesis in the diabetic wound. Adv Skin Wound Care. 2017;30(1):16-26. doi: 10.1097/01.ASW.0000504758.86737.76, PMID 27984270.

Zinder R, Cooley R, Vlad LG, Molnar JA. Vitamin a and wound healing. Nutr Clin Pract. 2019;34(6):839-49. doi: 10.1002/ncp.10420, PMID 31697447.

Singh MP, Sarangdevot YS, Sisodia SS. Wound healing activity of the whole plant of Momordica charantia linn. in rats. Indian Drugs. 2018;55(11):64-70. doi: 10.53879/id.55.11.11317.

Albaugh VL, Mukherjee K, Barbul A. Proline precursors and collagen synthesis: biochemical challenges of nutrient supplementation and wound healing. J Nutr. 2017 Nov;147(11):2011-7. doi: 10.3945/jn.117.256404, PMID 28978679.

Panda BC, Mondal S, Devi KS, Maiti TK, Khatua S, Acharya K. Pectic polysaccharide from the green fruits of Momordica charantia (karela): structural characterization and study of immunoenhancing and antioxidant properties. Carbohydr Res. 2015 Jan 12;401:24-31. doi: 10.1016/j.carres.2014.10.015, PMID 25464078.

Pullar JM, Carr AC, Vissers MC. The roles of vitamin C in skin health. Nutrients. 2017 Aug;9(8):866. doi: 10.3390/nu9080866, PMID 28805671.

De Phillipo NN, Aman ZS, Kennedy MI, Begley JP, Moatshe G, LA Prade RF. Efficacy of vitamin C supplementation on collagen synthesis and oxidative stress after musculoskeletal injuries: a systematic review. Orthop J Sports Med. 2018 Oct;6(10):2325967118804544. doi: 10.1177/2325967118804544, PMID 30386805.

Varani J, Warner RL, Gharaee Kermani M, Phan SH, Kang S, Chung JH. Vitamin a antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin. J Invest Dermatol. 2000 Mar;114(3):480-6. doi: 10.1046/j.1523-1747.2000.00902.x, PMID 10692106.

Yuliana B, Sartini S, Djide N, Djabir YY. Wound healing effect of snakehead fish (Channa striata) mucus containing transdermal patch. J Appl Pharm Sci. 2022;12(7):171-83. doi: 10.7324/JAPS.2022.120717.

Fajri UN, Hadisaputro S, Soejoenoes A. The effect of snake fish extract (Channa striata) on post-cesarean section wound status in postpartum anemia mothers. Indones J Med. 2018;3(2):84-8. doi: 10.26911/theijmed.2018.03.02.04.