Horse Chestnut (Aesculus hippocastanum) and Varicose veins: evidence and sources

Background Conservative therapy of chronic venous insufficiency (CVI) consists largely of compression treatment. However, this often causes discomfort and has been associated with poor compliance. Therefore, oral drug treatment is an attractive option. This is an update of a Cochrane review first published in 2002 and updated in 2004, 2006, 2008 and 2010. Objectives To review the efficacy and safety of oral horse chestnut seed extract (HCSE) versus placebo, or reference therapy, for the treatment of CVI. Search methods For this update the Cochrane Peripheral Vascular Diseases Review Group searched their Specialised Register (last searched June 2012) and CENTRAL (Issue 5, 2012). For the previous versions of the review the authors searched AMED (inception to July 2005) and Phytobase (inception to January 2001) for randomised controlled trials (RCTs) of HCSE for CVI. Manufacturers of HCSE preparations and experts on the subject were contacted for published and unpublished material. There were no restrictions on language. Selection criteria RCTs comparing oral HCSE mono-preparations with placebo, or reference therapy, in people with CVI. Trials assessing HCSE as one of several active components in a combination preparation, or as a part of a combination treatment, were excluded. Data collection and analysis Both authors independently selected the studies and, using a standard scoring system, assessed methodological quality and extracted data. Disagreements concerning evaluation of individual trials were resolved through discussion. Main results Overall, there appeared to be an improvement in CVI related signs and symptoms with HCSE compared with placebo. Leg pain was assessed in seven placebo-controlled trials. Six reported a significant reduction of leg pain in the HCSE groups compared with the placebo groups, while another reported a statistically significant improvement compared with baseline. One trial suggested a weighted mean difference (WMD) of 42.4 mm (95% confidence interval (CI) 34.9 to 49.9) measured on a 100 mm visual analogue scale. Leg volume was assessed in seven placebo-controlled trials. Six trials (n = 502) suggested a WMD of 32.1ml (95% CI 13.49 to 50.72) in favour of HCSE compared with placebo. One trial indicated that HCSE may be as effective as treatment with compression stockings. Adverse events were usually mild and infrequent. Authors' conclusions The evidence presented suggests that HCSE is an efficacious and safe short-term treatment for CVI. However, several caveats exist and larger, definitive RCTs are required to confirm the efficacy of this treatment option.

Chronic venous disease (CVD) is a prevalent condition that results from venous hypertension and leads to a variety of symptoms including leg pain, swelling, and venous ulcers. The condition significantly impacts quality of life (QoL) and imposes a burden on healthcare systems. Venoactive drugs (VADs) can manage CVD symptoms by improving venous tone, reducing inflammation, and enhancing microcirculation. In this review, six experts from Latin America provide a critical appraisal of the evidence supporting the use of VADs in CVD management. The review evaluates the efficacy of various VADs, including micronized purified flavonoid fraction (MPFF), rutosides, calcium dobesilate, sulodexide, horse chestnut seed extract, and red vine leaf extract. MPFF demonstrated robust efficacy in randomized controlled trials, significantly reducing symptoms such as pain, leg heaviness, and edema, and improving QoL. Other VADs, such as rutosides and calcium dobesilate, showed varying degrees of effectiveness, though the quality of supporting evidence remains inconsistent. This review also highlights variations in international guidelines - some recommending VADs more strongly than others, with MPFF emerging as the preferred option, supported by high-quality evidence. However, further research is necessary to clarify the role of other VADs and provide more definitive guidance on their use in clinical practice. PLAIN LANGUAGE SUMMARY: Chronic venous disease (CVD) is a condition that affects the veins in the legs, causing pain, swelling, and other symptoms like heaviness and cramping. It can also lead to more severe issues such as skin changes and ulcers. CVD is common and can greatly reduce a person's quality of life (QoL). It can also place a significant burden on healthcare systems. Venoactive drugs, or VADs, are medicines that help improve blood flow in the veins, reduce swelling, and ease inflammation. These drugs are used to alleviate CVD symptoms, especially when other conservative treatments, like compression stockings, are insufficient. This review describes the published evidence about different types of VADs and their effectiveness in CVD. Some drugs, like micronized purified flavonoid fraction (MPFF), have been shown to be particularly effective in reducing leg pain, swelling, and heaviness, as well as helping to improve the QoL of people with CVD. Other VADs, including rutosides, calcium dobesilate, and horse chestnut seed extract, have demonstrated clinical efficacy. Different medical guidelines for treating CVD from around the world recommend using VADs, though with some discrepancies on recommendation gradings. While MPFF is referred to in these guidelines as a leading option, further research is needed to better understand how different VADs can be used most effectively in treating CVD.

Background Chronic venous disease (CVD) is a major global health issue, affecting millions of people and contributing to significant morbidity and economic strain. The condition's pathophysiology is complex, involving both mechanical and biochemical processes that lead to venous reflux, obstruction, and chronic inflammation. This review focuses on the role of venoactive compounds (VACs), also known as venoactive drugs in Europe and other parts of the world, in managing CVD. The aim was to review the scientific evidence and to define the role of VACs within the comprehensive treatment algorithm for CVD, alongside established and well adopted interventional therapies and noninterventional therapies such as compression. Methods The review of the scientific evidence was done on VACs mechanism of action and efficacy in alleviating CVD symptoms, reducing swelling or venous edema, and improving healing of venous leg ulcers. Whenever available, systematic reviews, meta-analyses and randomized controlled trials were used. The quality of evidence assessment followed the GRADE methodology from A (high), B (moderate), to C (low to very low) quality. Results Venoactive drugs or compounds share similar effects, such as sealing the endothelial barrier, enhancing lymphatic drainage, reducing edema, improving venous tone, inhibiting leukocyte adhesion to vein walls/valves and inflammatory mediator release, lowering blood viscosity, and promoting red blood cell flexibility. Scientific evidence on the VACs effectiveness on CVD symptoms (pain, cramps, and heaviness) and swelling or edema have shown some variability. Micronized purified flavonoid fraction (MPFF) and Ruscus extract combined with hesperidin methyl chalcone and ascorbic acid had the highest, mostly level A, quality of evidence. In venous leg ulcers, micronized purified flavonoid fraction, sulodexide, and pentoxifylline were the most effective adjunctive treatments, with evidence level A. Conclusions The existing scientific evidence provides a strong rationale for incorporating VACs into a comprehensive treatment plan for CVD, alongside established interventional therapies and noninterventional approaches like compression, to optimize patient outcomes and improve quality of life.

The bark of Aesculus hippocastanum is an herbal remedy used in conditions connected with vascular insufficiency; however, there is a lack of data concerning its mechanisms of action. The present work is a preliminary investigation into some of the potential directions of the bark activity. The phytochemically (qualitative UHPLC-PDA-MS/MS and quantitative UHPLC-PDA assays) characterized extract and its four main constituents (esculin, fraxin, (‒)-epicatechin and procyanidin A2) were first evaluated in terms of their antioxidant capacity. All analytes demonstrated dose-dependent scavenging potential towards the most common in vivo oxidants, with particularly advantageous capacity of the extract and its flavan-3-ol constituents against peroxynitrite (3.37-13.26 mmol AA/g), hydroxyl radical (5.03-8.91 mmol AA/g) and superoxide radical (3.50-5.50 mmol AA/g). Moreover, even at low concentrations (1-5 µg/mL), they protected components of human plasma against oxidative damage inflicted by peroxynitrite, preventing oxidation of plasma protein thiols and diminishing the tyrosine nitration and lipid peroxidation. High efficiency of the analytes was also demonstrated in preventing the peroxynitrite-induced nitrative changes of fibrinogen (up to 80% inhibition for (‒)-epicatechin at 50 µg/mL), an important protein of coagulation cascade. Additionally, the extract and its constituents had, at most, moderate inhibitory activity towards platelet aggregation induced by ADP and only negligible influence on clotting times. The results show that, among the investigated properties, the antioxidant activity might, to the highest extent, be responsible for the bark efficacy in vascular disorders, thus supporting its application in those conditions; they also indicate the directions for future research that would allow for better understanding of the bark activity.