Biochemical Evaluation of Jihua Hemostatic Suppository in Hemorrhagic Internal Hemorrhoids: Modulation of Xpo1, VEGF, and Collagen I/III Expression and Inflammatory Biomarkers
Biochemical Modulation by Jihua Suppository in Hemorrhagic Hemorrhoids
Abstract
Background: Hemorrhagic internal hemorrhoids involve abnormal vascular remodeling, inflammatory activation, and extracellular matrix dysregulation. Exportin-1 (Xpo1), vascular endothelial growth factor (VEGF), and collagen types I and III are key biochemical markers associated with these processes. This study aimed to evaluate the therapeutic efficacy of Jihua Hemostatic Suppository compared with Gangtai Suppository and to investigate their differential effects on biochemical and inflammatory parameters in patients with hemorrhagic internal hemorrhoids.
Methods: A total of 98 patients diagnosed with hemorrhagic internal hemorrhoids were enrolled between January 2024 and January 2025 and randomly divided into two groups (n = 49 each) using the envelope randomization method. The Jihua group received Jihua Hemostatic Suppository, whereas the control group received Gangtai Suppository for two weeks. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were determined by ELISA. Xpo1 levels were measured by ELISA, VEGF by chemiluminescence assay, and collagen types I and III by the hydroxyproline method. Clinical efficacy, traditional Chinese medicine (TCM) syndrome scores, and adverse reactions were also recorded.
Results: The total effective rate in the Jihua group (93.88%) was significantly higher than that in the Gangtai group (77.55%) (χ² = 5.968, P = 0.015). After treatment, the Jihua group showed markedly lower serum IL-6 (70.50 ± 5.82 ng/mL), CRP (23.06 ± 2.71 mg/L), and TNF-α (60.81 ± 5.72 ng/mL) levels compared with the Gangtai group (P < 0.001). Biochemically, Xpo1, VEGF, collagen I, and collagen III concentrations were significantly reduced in the Jihua group (12.31 ± 1.35 ng/mL, 389.64 ± 34.32 pg/mL, 154.39 ± 15.19 pg/L, and 36.13 ± 3.06 μg/L, respectively) compared with the Gangtai group (P < 0.05). The incidence of adverse reactions was lower with Jihua suppository (4.08%) than with Gangtai suppository (20.41%) (χ² = 4.242, P = 0.039).
Conclusion: Jihua Hemostatic Suppository exerts superior therapeutic and biochemical effects in hemorrhagic internal hemorrhoids compared with Gangtai Suppository. Its efficacy is likely mediated by suppression of the Xpo1/NF-κB inflammatory axis, inhibition of VEGF-driven angiogenesis, and normalization of collagen I/III-dependent extracellular matrix remodeling. These findings highlight the value of integrating biochemical biomarkers into clinical assessment of hemorrhoidal disease and suggest Xpo1, VEGF, and collagen I/III as potential molecular indicators of treatment efficacy.
References
2. Mott T, Latimer K, Edwards C. Hemorrhoids: Diagnosis and Treatment Options. Am Fam Physician 2018; 97(3): 172-9.
3. Lew FH, Ailabouni LD. Rubber Band Ligation of Internal Hemorrhoids. Dis Colon Rectum 2023; 66(9): e950.
4. Zhang G, Liang R, Wang J, Ke M, Chen Z, Huang J, et al. Network meta-analysis of randomized controlled trials comparing the procedure for prolapse and hemorrhoids, Milligan-Morgan hemorrhoidectomy and tissue-selecting therapy stapler in the treatment of grade III and IV internal hemorrhoids(Meta-analysis). Int J Surg 2020; 74(53-60.
5. Talaie R, Torkian P, Moghadam AD, Tradi F, Vidal V, Sapoval M, et al. Hemorrhoid embolization: A review of current evidences. Diagn Interv Imag 2022; 103(1): 3-11.
6. Sninsky JA, Galanko J, Sandler RS, Peery AF. Diverticulosis Is Associated With Internal Hemorrhoids on Colonoscopy: Possible Clues to Etiology. Clin Gastroenterol H 2023; 21(4): 1097-9.
7. Han X, Xia F, Chen G, Sheng Y, Wang W, Wang Z, et al. Superior rectal artery embolization for bleeding internal hemorrhoids. Tech Coloproctol 2021; 25(1): 75-80.
8. Rakinic J, Poola VP. Hemorrhoids and fistulas: new solutions to old problems. Curr Prob Surg 2014; 51(3): 98-137.
9. Qu C, Zhang F, Wang W, Gao F, Lin W, Zhang H, et al. Endoscopic polidocanol foam sclerobanding for the treatment of grade II-III internal hemorrhoids: A prospective, multi-center, randomized study. World J Gastroentero 2024; 30(27): 3326-35.
10. Gan C, Mu Y, Ali SSF, Shi X, Jiang S, Wang Z, et al. The processed Sanguisorba officinalis L. triterpenoids prevent colon cancer through the TNF-alpha/NF-kappaB signaling pathway, combined with network pharmacology, molecular simulation dynamics and experimental verification. Front Immunol 2025; 16: 1605326.
11. Lohsiriwat V, Sheikh P, Bandolon R, Ren D, Roslani AC, Schaible K, et al. Recurrence Rates and Pharmacological Treatment for Hemorrhoidal Disease: A Systematic Review. Adv Ther 2023; 40(1): 117-32.
12. Orkin BA, Schwartz AM, Orkin M. Hemorrhoids: what the dermatologist should know. J Am Acad Dermatol 1999; 41(3 Pt 1): 449-56.
13. Gkegkes ID, Dalavouras N, Iavazzo C, Stamatiadis AP. Sweetening ... the pain: The role of sugar in acutely prolapsed haemorrhoids. Clin Ter 2021; 172(6): 520-2.
14. Emile SH, Elfeki H, Sakr A, Shalaby M. Transanal hemorrhoidal dearterialization (THD) versus stapled hemorrhoidopexy (SH) in treatment of internal hemorrhoids: a systematic review and meta-analysis of randomized clinical trials. Int J Colorectal Dis 2019; 34(1): 1-11.
15. Ohning GV, Machicado GA, Jensen DM. Definitive therapy for internal hemorrhoids--new opportunities and options. Rev Gastroenterol Disord 2009; 9(1): 16-26.
16. Nunoo-Mensah JW, Kaiser AM. Stapled hemorrhoidectomy. Am J Surg 2005; 190(1): 127-30.
17. Jin L, Yang H, Qin K, Li Y, Cui C, Wu R, et al. Efficacy of modified rubber band ligation in the treatment of grade III internal hemorrhoids. Ann Palliat Med 2021; 10(2): 1191-7.
18. Kisaki S, Igarashi T, Ashida H, Furuhashi H, Ojiri H. The Utility of Submucosal Linear Enhancement on Dynamic Computed Tomography for Patients With Internal Hemorrhoids. J Comput Assist Tomo 2022; 46(5): 688-92.
19. Gachabayov M, Angelos G, Orangio G, Abcarian H, Bergamaschi R. Transanal Hemorrhoidal Dearterialization With Mucopexy Versus Ferguson Hemorrhoidectomy for Prolapsed Internal Hemorrhoids: A Multicenter Prospective Study. Ann Surg 2023; 278(3): 376-82.
20. Alonso-Coello P, Mills E, Heels-Ansdell D, Lopez-Yarto M, Zhou Q, Johanson JF, et al. Fiber for the treatment of hemorrhoids complications: a systematic review and meta-analysis. Am J Gastroenterol 2006; 101(1): 181-8.
21. Zhang K, Liu H, Liu P, Feng Q, Gan L, Yao L, et al. Positive efficacy of Lactiplantibacillus plantarum MH-301 as a postoperative adjunct to endoscopic sclerotherapy for internal hemorrhoids: a randomized, double-blind, placebo-controlled trial. Food Funct 2023; 14(18): 8521-32.
Copyright (c) 2025 Chao Wang, Yajun Kang, Ye Wang, Yujie Liu, Mengli Shi, Xiaoming Liu, Hao Jiao

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