Background: Chronic venous insufficiency (CVI) is a prevalent and incurable condition that can be managed through both medical and surgical interventions. Objective: To compare the safety and efficacy of a combination of Aesculushippocastanum, Polygonumacre, Smilaxpapyracea, and rutin (Group A; nA = 60) versus a combination of diosmin-hesperidin (Group B; nB = 60), over a 90-day treatment period, in patients with symptoms consistent with CVI. Methods: Efficacy and safety were assessed using both self-paired and comparative study designs. Study endpoints included: 1) Severity of venous symptoms measured by the Visual Analogue Scale (VAS), 2) Quality of life via the CIVIQ-20 score, 3) Physician’s assessment score, 4) Patient’s self-assessment score, and 5) Ease of swallowing the pharmaceutical form, assessed by VAS. Safety profiles were also evaluated. Results: The Group A combination was statistically non-inferior to the Group B combination across all study endpoints, including venous symptom severity, quality of life, and both physician and patient assessments. Group A’s formulation was reported to perform better on quality-of-life (CIVIQ-20 score-Visit 3) (p < 0.05) and was easier to swallow (p < 0.05). Both treatments were well tolerated. Conclusion: Both regimens were safe and effective, with Group A showing better general performance in relation to Group B.
References
[1]
Dickson, S., Gallagher, J., McIntyre, L., Suter, A. and Tan, J. (2004) An Open Study to Assess the Safety and Efficacy of Aesculus hippocastanum Tablets (Aesculaforce® 50 Mg) in the Treatment of Chronic Venous Insufficiency. Journal of Herbal Pharmacotherapy, 4, 19-32. https://doi.org/10.1080/j157v04n02_03
[2]
Diehm, C., Trampisch, H.J., Lange, S. and Schmidt, C. (1996) Comparison of Leg Compression Stocking and Oral Horse-Chestnut Seed Extract Therapy in Patients with Chronic Venous Insufficiency. The Lancet, 347, 292-294. https://doi.org/10.1016/s0140-6736(96)90467-5
[3]
European Medicines Agency (2020) Note for Guidance on European Union Herbal Mono-Graph on Aesculus hippocastanum L., Semen.
[4]
Gallelli, L. (2019) Escin: A Review of Its Anti-Edematous, Anti-Inflammatory, and Venotonic Properties. Drug Design, Development and Therapy, 13, 3425-3437. https://doi.org/10.2147/dddt.s207720
[5]
Idris, S., Mishra, A. and Khushtar, M. (2020) Phytochemical, Ethanomedicinal and Pharmacological Applications of Escin from Aesculus hippocastanum L. towards Future Medicine. Journal of Basic and Clinical Physiology and Pharmacology, 31, Article 20190115. https://doi.org/10.1515/jbcpp-2019-0115
[6]
NIH (National Institutes of Health) (2021) Horse Chestnut. https://www.nccih.nih.gov/health/horse-chestnut
[7]
Ottillinger, B. and Greeske, K. (2001) Rational Therapy of Chronic Venous Insufficiency—Chances and Limits of the Therapeutic Use of Horse-Chestnut Seeds Extract. BMC Cardiovascular Disorders, 1, Article No. 5. https://doi.org/10.1186/1471-2261-1-5
[8]
Paris, C.A.M. and Soares, R.M.B. (1993) Efficacy and Safety on Use of Dried Horse Chestnut Extract in the Treatment of Chronic Venous Insufficiency of the Limbs. Revista Brasileira de Medicina, 50, 1563-1565.
[9]
Pittler, M.H. and Ernst, E. (2012) Horse Chestnut Seed Extract for Chronic Venous Insufficiency. Cochrane Database of Systematic Reviews, No. 11, CD003230. https://doi.org/10.1002/14651858.cd003230.pub4
[10]
Siebert, U., Brach, M., Sroczynski, G., et al. (2002) Efficacy, Routine Effectiveness, and Safety of Horsechestnut Seed Extract in the Treatment of Chronic Venous Insufficiency. A Meta-Analyis of Randomized Controlled Trials and Large Observational Studies. International Angiology, 21, 305-315.
Suter, A., Bommer, S. and Rechner, J. (2006) Treatment of Patients with Venous Insufficiency with Fresh Plant Horse Chestnut Seed Extract: A Review of 5 Clinical Studies. Advances in Therapy, 23, 179-190. https://doi.org/10.1007/bf02850359
[13]
Underland, V., Sæterdal, I. and Nilsen, E.S. (2012) Cochrane Summary of Findings: Horse Chestnut Seed Extract for Chronic Venous Insufficiency. Global Advances in Health and Medicine, 1, 122-123. https://doi.org/10.7453/gahmj.2012.1.1.018
[14]
Park, G., Kim, T., Kim, J.H. and Oh, M.S. (2014) Antioxidant Effects of the Sarsaparilla via Scavenging of Reactive Oxygen Species and Induction of Antioxidant Enzymes in Human Dermal Fibroblasts. Environmental Toxicology and Pharmacology, 38, 305-315. https://doi.org/10.1016/j.etap.2014.06.009
[15]
Ministério da Saúde e Anvisa (2014) Monografia das espécies polygonum hidropiperoides e Polygonum acre (erva-de-bicho).
[16]
Simões, C.M.O., Schenkel, E.P., Gosman, G., et al. (1999) Farmacognosia. Da planta ao medicamento. 5a edição. Editora da UFSC/UFRGS Editora.
[17]
Rutin (2008) PDR for Nutritional Supplements. 2nd Edition.
[18]
Altinterím, B. (2014) Citrus, Rutin and on Their Vein Permeability Effects. Research Journal of Agricultural and Environmental Management, 3, 80-81.
[19]
Chua, L.S. (2013) A Review on Plant-Based Rutin Extraction Methods and Its Pharmacological Activities. Journal of Ethnopharmacology, 150, 805-817. https://doi.org/10.1016/j.jep.2013.10.036
[20]
Ganeshpurkar, A. and Saluja, A.K. (2017) The Pharmacological Potential of Rutin. Saudi Pharmaceutical Journal, 25, 149-164. https://doi.org/10.1016/j.jsps.2016.04.025
[21]
Batcharov, I.V., Batselova, G. and Damyanov, I.I. (2010) One-Year Diosmin Therapy (600 Mg) in Patients with Chronic Venous Insufficiency—Results and Analysis. Journal of Biomedical and Clinical Research, 3, 51-54.
[22]
Cazaubon, M., Bailly, C., Ducros, E., et al. (2011) Acceptability, Efficacy and Safety of Two Pharmaceutical Forms of Diosmin 600 Mg in Patients with Chronic Venous Disease: A Randomized Comparative Multicenter Study. Angiology, 1-6.
[23]
Cova, D. and De Angelis, L. (1990) Pharmacokinetic and Metabolic Characteristics of Diosmine after Administration in Man. European Journal of Pharmacology, 183, 1854-1855. https://doi.org/10.1016/0014-2999(90)92185-l
[24]
Steinbruch, M., Geller, M., Kaufman, R., et al. (2015) Use of Pure Diosmin 600 Mg in Chronic Venous Disease: A Review of the Literature. Revista Brasileira de Medicin, 72, 307-314.
[25]
Tripoli, E., Guardia, M.L., Giammanco, S., Majo, D.D. and Giammanco, M. (2007) Citrus Flavonoids: Molecular Structure, Biological Activity and Nutritional Properties: A Review. Food Chemistry, 104, 466-479. https://doi.org/10.1016/j.foodchem.2006.11.054
[26]
Beebe-Dimmer, J.L., Pfeifer, J.R., Engle, J.S. and Schottenfeld, D. (2005) The Epidemiology of Chronic Venous Insufficiency and Varicose Veins. Annals of Epidemiology, 15, 175-184. https://doi.org/10.1016/j.annepidem.2004.05.015
[27]
DePopas, E. and Brown, M. (2018) Varicose Veins and Lower Extremity Venous Insufficiency. Seminars in Interventional Radiology, 35, 56-61. https://doi.org/10.1055/s-0038-1636522
[28]
Santler, B. and Goerge, T. (2017) Chronic Venous Insufficiency—A Review of Pathophysiology, Diagnosis, and Treatment. JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 15, 538-556. https://doi.org/10.1111/ddg.13242
[29]
Youn, Y.J. and Lee, J. (2019) Chronic Venous Insufficiency and Varicose Veins of the Lower Extremities. The Korean Journal of Internal Medicine, 34, 269-283. https://doi.org/10.3904/kjim.2018.230
[30]
Steinbruch, M., Nunes, C., Gama, R., Kaufman, R., Gama, G., Suchmacher Neto, M., et al. (2020) Is Nonmicronized Diosmin 600 Mg as Effective as Micronized Diosmin 900 Mg Plus Hesperidin 100 Mg on Chronic Venous Disease Symptoms? Results of a Noninferiority Study. International Journal of Vascular Medicine, 2020, Article ID: 4237204. https://doi.org/10.1155/2020/4237204