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CLINICAL RESEARCH
Synergistic therapeutic approach for hemorrhoids: integrating mesenchymal stem cells with diosmin-hesperidin to target tissue edema and inflammation
1
Doctoral program of Medical Sciences, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia
2
Department of Surgery, Faculty of Medicine, Universitas Muhammadiyah Purwokerto, Purwokerto, Indonesia
3
Department of Oral and Maxillofacial Pathology, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia
4
Department of Obstetrics and Gynaecology, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia
5
Department of Obstetrics and Gynaecology, Moewardi General Hospital, Surakarta, Indonesia
Submission date: 2024-01-02
Final revision date: 2024-01-29
Acceptance date: 2024-01-30
Online publication date: 2024-10-30
Corresponding author
M. Hidayat Budi Kusumo
Doctorate student of Medical Sciences, Faculty of medicine, Universitas Sebelas Maret, Surakarta, Indonesia
Doctorate student of Medical Sciences, Faculty of medicine, Universitas Sebelas Maret, Surakarta, Indonesia
KEYWORDS
mesenchymal stem cellscroton oilhemorrhoidinflammationmicronized purified flavonoid fractiondiosmin-hesperidin
TOPICS
ABSTRACT
Introduction:
Mesenchymal stem cells (MSCs) have promising regenerative properties in tissue repair and anti-inflammatory responses. This study aimed to investigate the effects of MSCs and their combination with micronized purified flavonoid fraction (MPFF) in a croton oil-induced hemorrhoids model on tissue edema, inflammation, and underlying molecular mechanisms.
Material and methods:
MSCs were isolated and characterized for their adherence, differentiation capacity, and immunophenotyping. Croton oil-induced hemorrhoid mouse models were established to assess tissue edema, inflammation, tumor necrosis factor (TNF-α) expression, transforming growth factor-β (TGF-β) expression, collagen ratio, and MMP-9 activity. The effects of MSCs and their combination with MPFF (diosmin-hesperidin) were evaluated through histological examinations, western blot analysis, and gelatin zymography.
Results:
Characterization confirmed the MSCs’ plastic adherence, osteogenic differentiation potential, and immunophenotype (positive for CD90 and CD29, negative for CD45 and CD31). Treatment with MSCs alone or in combination with MPFF significantly reduced tissue edema, inflammation, TNF-α expression, and MMP-9 activity. Additionally, MSCs increased TGF-β expression, and collagen type I/III ratio, and accelerated wound healing by resolving inflammation.
Conclusions:
These findings suggest that MSCs play a crucial role in modulating TNF-α, TGF-β, collagen remodeling, and MMP-9 activity, highlighting their promising role in hemorrhoid treatment and wound healing processes. Further research is warranted to fully elucidate the intricate mechanisms and optimize MSC-based therapies for clinical applications in hemorrhoidal disease management.
Mesenchymal stem cells (MSCs) have promising regenerative properties in tissue repair and anti-inflammatory responses. This study aimed to investigate the effects of MSCs and their combination with micronized purified flavonoid fraction (MPFF) in a croton oil-induced hemorrhoids model on tissue edema, inflammation, and underlying molecular mechanisms.
Material and methods:
MSCs were isolated and characterized for their adherence, differentiation capacity, and immunophenotyping. Croton oil-induced hemorrhoid mouse models were established to assess tissue edema, inflammation, tumor necrosis factor (TNF-α) expression, transforming growth factor-β (TGF-β) expression, collagen ratio, and MMP-9 activity. The effects of MSCs and their combination with MPFF (diosmin-hesperidin) were evaluated through histological examinations, western blot analysis, and gelatin zymography.
Results:
Characterization confirmed the MSCs’ plastic adherence, osteogenic differentiation potential, and immunophenotype (positive for CD90 and CD29, negative for CD45 and CD31). Treatment with MSCs alone or in combination with MPFF significantly reduced tissue edema, inflammation, TNF-α expression, and MMP-9 activity. Additionally, MSCs increased TGF-β expression, and collagen type I/III ratio, and accelerated wound healing by resolving inflammation.
Conclusions:
These findings suggest that MSCs play a crucial role in modulating TNF-α, TGF-β, collagen remodeling, and MMP-9 activity, highlighting their promising role in hemorrhoid treatment and wound healing processes. Further research is warranted to fully elucidate the intricate mechanisms and optimize MSC-based therapies for clinical applications in hemorrhoidal disease management.
REFERENCES (50)
1.
Brown SR. Haemorrhoids: an update on management. Ther Adv Chronic Dis 2017; 8: 141-7.
2.
Jakubauskas M, Poskus T. Evaluation and management of hemorrhoids. Dis Colon Rectum 2020; 63: 420-4.
3.
Sun Z, Migaly J. Review of hemorrhoid disease: presentation and management. Clin Colon Rectal Surg 2016; 29: 22-9.
4.
Budiono BP, Susilaningsih N, Prasetyo SA, Chionardes MA, Riwanto I. Challenge in prominent grade IV hemorrhoid management: a case report. Bali Med J 2023; 12: 442-4.
5.
Kibret AA, Oumer M, Moges AM. Prevalence and associated factors of hemorrhoids among adult patients visiting the surgical outpatient department in the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. PLoS One 2021; 16: e0249736.
6.
Lohsiriwat V. Treatment of hemorrhoids: a coloproctologist’s view. World J Gastroenterol 2015; 21: 9245-52.
7.
Lalisang TJ. Hemorrhoid: pathophysiology and surgical management literature review. N Ropanasuri J Surg 2016; 1: 31-6.
8.
Mihai DP, Seremet OC, Nitulescu G, et al. Evaluation of natural extracts in animal models of pain and inflammation for a potential therapy of hemorrhoidal disease. Sci Pharm 2019; 87: 14.
9.
Dubey T, Bhanukiran K, Prasad SK, Hemalatha S. Optimization of extraction process and anti-hemorrhoidal activity of Blumea lacera (burm.f.) dc. leaves in croton oil-induced hemorrhoid model. Pharmacogn Mag 2023; 19: 709-19.
10.
Zhou M, Jin W, Li P, Wang R, Guo X. Traditional Chinese medicine in the treatment of hemorrhoids – a review of preparations used and their mechanism of action. Front Pharmacol 2023; 14: 1270339.
11.
Azeemuddin M, Viswanatha GL, Rafiq M, et al. An improved experimental model of hemorrhoids in rats: evaluation of antihemorrhoidal activity of an herbal formulation. ISRN Pharmacol 2014; 2014: 1-7.
12.
Margetis N. Pathophysiology of internal hemorrhoids. Ann Gastroenterol 2019; 32: 264-72.
13.
Lohsiriwat V. Hemorrhoids: from basic pathophysiology to clinical management Varut Lohsiriwat. World J Gastroenterol 2012; 18: 2009-17.
14.
Yamana T. Japanese Practice Guidelines for anal disorders. I. Hemorrhoids. J Anus Rectum Colon 2017; 1: 89-99.
15.
Hu WS, Lin CL. Hemorrhoid is associated with increased risk of peripheral artery occlusive disease: a nationwide cohort study. J Epidemiol 2017; 27: 574-7.
16.
Serra R, Gallelli L, Grande R, et al. Hemorrhoids and matrix metalloproteinases: a multicenter study on the predictive role of biomarkers. Surgery (United States) 2015; 159: 487-94.
17.
Hartanto MM, Prajoko YW, Putra A, Amalina ND. The combination of mesenchymal stem cells and bovine colostrum in reducing -SMA expression and NLR levels in wistar rats after 50% fibrotic liver resection. Open Access Maced J Med Sci 2022; 10(A): 1634-9.
18.
Hamra NF, Putra A, Tjipta A, Amalina ND, Nasihun T. Hypoxia mesenchymal stem cells accelerate wound closure improvement by controlling -smooth muscle actin expression in the full-thickness animal model. Open Access Maced J Med Sci 2021; 9: 35-41.
19.
Utami A, Putra A, Wibowo JW, Amalina ND, Satria Irawan RC. Hypoxic secretome mesenchymal stem cells inhibiting interleukin-6 expression prevent oxidative stress in type 1 diabetes mellitus. Med Glas (Zenica) 2023; 20(2). doi:10.17392/1538-23.
20.
Prajoko YW, Putra A, Dirja BT, Muhar AM, Amalina ND. The ameliorating effects of MSCs in controlling Treg-mediated B-cell depletion by indoleamine 2, 3-dioxygenase induction in PBMC of SLE patients. Open Access Maced. J Med Sci 2022; 10: 6-11.
21.
Drawina P, Putra A, Nasihun T, Prajoko YW, Dirja BT, Amalina ND. Increased serial levels of platelet-derived growth factor using hypoxic mesenchymal stem cell-conditioned medium to promote closure acceler- ation in a full-thickness wound. Indones J Biotechnol 2022; 27: 36.
22.
Restimulia L, Ilyas S, Munir D, et al. Rats’ umbilical-cord mesenchymal stem cells ameliorate mast cells and Hsp70 on ovalbumin-induced allergic rhinitis rats. Med Glas 2022; 19(1). doi:10.17392/1421-21.
23.
Hidayat M, Kusumo B, Husain SA, Amalina ND, Id HA. Secretome MSCs restore -smooth muscle actin protein tissue expression in croton oil-induced hemorrhoid rats. Int J Cell Biomed Sci 2023; 2.
24.
Carvello M, Lightner A, Yamamoto T, Kotze PG, Spinelli A. Mesenchymal stem cells for perianal Crohn’s disease. Cells 2019; 8: 764.
25.
Daryanti E, Putra A, Sumarawati T, Amalina ND, Prasetio A, Sidiq HA. The comparison of normoxic and hypoxic mesenchymal stem cells in regulating platelet-derived growth factors and collagen serial levels in skin excision animal models. Open Access Maced J Med Sci 2023; 11: 181-7.
26.
Mayasari YI, Subchan P, Putra A, et al. Secretome hypoxia mesenchymal stem cells inhibited ultraviolet radiation by inhibiting interleukin-6 through nuclear factor-kappa beta pathway in hyperpigmentation animal models. Open Access Maced J Med Sci 2023; 11: 188-94.
27.
Zukhiroh Z, Putra A, Chodidjah C, et al. Effect of secretome-hypoxia mesenchymal stem cells on regulating SOD and MMP-1 mRNA expressions in skin hyperpigmentation rats. Open Access Maced J Med Sci 2022; 10: 1-7.
28.
Fredianto M, Herman H, Ismiarto YD, et al. Secretome of hypoxia-preconditioned mesenchymal stem cells enhance the expression of HIF-1a and bFGF in a rotator cuff tear model. Med Glas 2023; 20: 242-8.
29.
Munir D, Nasution IP, Restimulia L, Putra A, Amalina ND. The role of mesenchymal stem cells in allergic rhinitis and its relationship with IL-10, plasma cells and regulatory T cells. Med Glas 2023; 20: 175-80.
30.
Nallajerla SK, Ganta S. Ethanolic leaf extract of moringa oleifera a potential agent for treatment of hemorrhoids and its evaluation in croton oil induced hemorrhoidal rats. J Drug Alcohol Res 2022; 11(7). doi:10.4303/jdar/236189.
31.
Jenie RI, Amalina ND, Hermawan A, Suzery M, Putra A, Meiyanto E. Caesalpinia sappan reduces the stemness of breast cancer stem cells involving the elevation of intracellular reactive oxygen species. Res Pharm Sci 2023; 18: 708-21.
32.
Darlan DM, Munir D, Putra A, et al. Revealing the decrease of indoleamine 2,3-dioxygenase as a major constituent for B cells survival post-mesenchymal stem cells co-cultured with peripheral blood mononuclear cell (PBMC) of systemic lupus erythematosus (SLE) patients. Med Glas 2022; 19(1). doi:10.17392/1414-21.
33.
Restimulia L, Ilyas S, Munir D, et al. The CD4+CD25+FoxP3+ regulatory T cells regulated by MSCs suppress plasma cells in a mouse model of allergic rhinitis. Med Arch 2021; 75: 256-61.
34.
Amalina ND, Salsabila IA, Zulfin UM, Jenie RI, Meiyanto E. In vitro synergistic effect of hesperidin and doxorubicin downregulates epithelial-mesenchymal transition in highly metastatic breast cancer cells. J Egypt Natl Canc Inst 2023; 35: 6.
35.
Ueha S, Shand FHW, Matsushima K. Cellular and molecular mechanisms of chronic inflammation-associated organ fibrosis. Front Immunol 2012; 3: 71.
36.
Liu T, Zhang L, Joo D, Sun SC. NF-B signaling in inflammation. Signal Transduct Target Ther 2017; 2: 17023.
37.
Lu B, Wang C, Wang M, et al. Molecular mechanism and therapeutic modulation of high mobility group box 1 release and action: an updated review. Expert Rev Clin Immunol 2014; 10: 713-27.
38.
Andersson U, Tracey KJ. HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol 2011; 29: 139-62.
39.
Sungkar T, Putra A, Lindarto D, Sembiring RJ. Intravenous umbilical cord-derived mesenchymal stem cells transplantation regulates hyaluronic acid and interleukin-10 secretion producing low-grade liver fibrosis in experimental rat. Med Arch 2020; 74: 177-82.
40.
Ikhsan R, Putra A, Munir D, Darlan DM, Suntoko B, Retno A. Mesenchymal stem cells induce regulatory T-cell population in human SLE. Bangladesh J Med Sci 2020; 19: 743-8.
41.
Masyithah Darlan D, Munir D, Karmila Jusuf N, Putra A, Ikhsan R, Alif I. In vitro regulation of IL-6 and TGF-ß by mesenchymal stem cells in systemic lupus erythematosus patients. Med Glas (Zenica) 2020; 17: 408-13.
42.
Mukti AI, Ilyas S, Warli SM, et al. Umbilical cord-derived mesenchymal stem cells improve TGF-, -SMA and collagen on erectile dysfunction in streptozotocin-induced diabetic rats. Med Arch 2022; 76: 4-11.
43.
Prayitno GD, Lestari K, Sartika CR, et al. Potential of mesenchymal stem cells and their secretomes in decreasing inflammation markers in polycystic ovary syndrome treatment: a systematic review. Medicines 2022; 10: 3.
44.
Rong X, Li J, Yang Y, Shi L, Jiang T. Human fetal skin-derived stem cell secretome enhances radiation-induced skin injury therapeutic effects by promoting angiogenesis. Stem Cell Res Ther 2019; 10: 383.
45.
Moradinasab S, Pourbagheri-Sigaroodi A, Zafari P, Ghaffari SH, Bashash D. Mesenchymal stromal/stem cells (MSCs) and MSC-derived extracellular vesicles in COVID-19-induced ARDS: mechanisms of action, research progress, challenges, and opportunities. Int Immunopharmacol 2021; 97: 107694.
46.
Landén NX, Li D, Ståhle M. Transition from inflammation to proliferation: a critical step during wound healing. Cell Mol Life Sci 2016; 73: 3861-85.
47.
Ishiuchi N, Nakashima A, Doi S, et al. Hypoxia-preconditioned mesenchymal stem cells prevent renal fibrosis and inflammation in ischemia-reperfusion rats. Stem Cell Res Ther 2020; 11: 130.
48.
Pers YM, Ruiz M, Noël D, Jorgensen C. Mesenchymal stem cells for the management of inflammation in osteoarthritis: state of the art and perspectives. Osteoarthritis Cartilage 2015; 23: 2027-35.
49.
Cheng Z, Wang L, Qu M, et al. Mesenchymal stem cells attenuate blood-brain barrier leakage after cerebral ischemia in mice. J Neuroinflammation 2018; 15: 135.
50.
Putra A, Alif I, Hamra N, et al. MSC-released TGF- regulate -SMA expression of myofibroblast during wound healing. J Stem Cells Regen Med 2020; 16: 73-9.
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| ISSN: | 1734-1922 |
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