Horse Chestnut

    Last Updated: September 28, 2022

    Horse Chestnut (Aesculus hippocastanum) is a plant extract with a group of molecules known as aescins, which are beneficial to circulatory health. Supplementation of horse chestnut appears to be beneficial for varicose veins and veinous insufficiency.

    Horse Chestnut is most often used for .


    Sources and Composition



    Aesculus hippocastanum (of the family hippocastanaceae[1]) is a plant commonly referred to as Horse Chestnut or Conker Tree. It is widely spread across the world due to having large environmental resiliance and the bark of branches, fruits, and seeds are usually used medicinally (the leaves are at times, but this is much less common[2]) while the bright white, yellow, or red flowers are mostly aesthetic. The oil extract of the fruits is sometimes used for neuralgic and rheumatic conditions specifically.[3]

    The 'seeds' themselves are medicinally referred to as semen hippocastani and they are covered by a large spiky husk[4] which is commonly referred to as the horse chestnut or buckeye.[5] The term buckeye actually refers to all seeds of the hippocastanaceae family, whereas actual chestnuts belong to the castanea genus.

    Aesculus hippocastanum is a tree which bears seeds in spiky husks that are known as horse chestnuts. The seeds are the main part of the plant used medicinally, although it appears all parts of the plant have at times been investigated or used for medicinal purposes

    Traditionally, the seeds have been mostly used medicinally for the treatment of hemorrhoids and circulatory health.[1] Lesser known uses include the treatment of rheumatism, bladder and gastrointestinal disorders, fever, and leg cramps (possible secondary to the circulatory effects).[1]

    Traditional usage of horse chestnut appears to be for hemorroids and circulatory health, particularly against blood pooling



    Horse chestnut (seeds) tends to contain:

    • Aescin, which is a series of triterpenoid glycosides broken into two subsets of β-aescins (main ones, known as aescin Ia and aescin Ib[1]) and the α-aescins (two aesceins known as isoaescin Ia and isoaescin Ib[1]). These glycosides are based off the protoaescigenin and barringtogenol C molecules.
    • The coumarin structures Aesculetin[1] and its glycoside Aesculin[1]
    • Scopoletin and its glycoside Fraxin[1]
    • Procyanidin A2[1]
    • Leucocyanidine[5]
    • Quercetin and its glycosides[1][6]
    • Kaempherol and its glycosides[1][6]
    • Tamarixetin as 3-O-β-d-glucopyranosyl(1→3)-O-β-d-xylopyranosyl-(1→2)-O-β-d-glucopyranoside[5]

    Whereas the leaves are known to contain:

    • Coumarins scopoletin (0.41% dry weight), aesculetin (0.13%), and fraxetin (0.05%)[2]
    • Kaempferol as the glycosides 3-O-α-arabinofuranoside, 3-O-β-glucopyranoside, 3-O-α-rhamnopyranoside, and 3-O-α-rhamnopyranosyl(1→6)-O-β-glucopyranoside[7]
    • Quercetin as the glycosides 3-O-α-arabinofuranoside, 3-O-β-glucopyranoside, and 3-O-α-rhamnopyranosyl(1→6)-O-β-glucopyranoside[7]

    The fruits consist of:

    • Oil (8.1% of fruit weight[3]) which is comprised of oleic acid (65.3%), linoleic (20.2%), palmitic (4.8%), and stearic (2.1%) acids[3][8] with trace linolenic[8]
    • Phospholipids (0.3%[3]) which are 36.9% Phosphatidylcholine and 13.2-13.9% phosphatidylethanolamine and phosphatidylinositol[3]
    • Sterols (1.2%[3]) with a sitosterol and stigmasterol content[9][10] with the majority (73.2% of sterols) being β-Sitosterol[3]
    • Vitamin E (627mg/kg[3]) mostly γ-Tocopherol (59%) and α-Tocopherol (40%) with trace tocotrienols[3]

    The four molecules collectively refered to as aescins (and the two referred to as β-aescins in particular) are the main bioactives in horse chestnut supplements. The coumarins, particular aesculin, are also thought to be somewhat bioactive

    Total flavonoids in horse chestnut seed powder (used for supplements) are up to 0.88%[5] or 0.3%[6] of the dry weight; the low contentration seen here may be due to losses in wastewater during processing, which can reach up to 2.58%.[5]

    The flavonoids are likely in too low quantities to really contribute significantly to the effects of a seed based supplement



    Structures and Properties

    The α and β subsets of aescin can be differentiated by their melting point, specific rotation, haemolytic index and solubility in water while the α-aescins can be converted into β-aescins by heating at 100C.[1] β-aescin has a molar mass of 1137.3g.[11]

    'Aescin' refers to the mixture of four steroidal saponins, where 'α-aescin' and 'β-aescin' both refer to two of the four saponins. The individual saponins in the α-aescin group are the two isoaescins (Ia and Ib) while the two in the β-aescin group are the aescins (Ia and Ib)


    Variants and Formulations

    There is a brand name known as Emospid which contains leucocyanidin from Horse Chestnut (100mg), various anthocyanins from bilberry (80mg bilberry standardized to 36% anthocyanins), and triterpenoids from Centella asiatica (30mg) for the treatment of venous disorders such as chronic venous insufficiency and acute hemorroidal crisis.[12]





    It was initially reported that the bioavailability of aescin was 12.5%[13] although subsequent studies in rats have reported bioavailabilities of less than 0.25%.[14]

    Aescins from horse chestnut appear to be poorly absorbed

    The differences in absorption rates and values with Aescorin® (standard form of horse chestnut with 50mg β-aescin) and Venostasin® (a delayed release formulation with 50mg β-aescin) is not significant.[15]



    In rats, both isolated aescin Ia and isoaescin Ia are absorbed at an oral intake of 4mg/kg (to max values of 7.1ng/mL and 43.8ng/mL, respectively).[14]

    Supplementation of 50mg β-aescin from horse chestnut reaches a Tmax value in just under three hours (2.3-2.9h) reaching an average Cmax of 16.9-17.3ng/mL with an AUC24h of 247.4-258.5ng/h/mL.[15]

    The exact peaks in plasma appear to be subject to a wide degree of interpersonal variability.[16]

    Twice daily supplementation of β-aescin (50mg) separated by 12 hours is enough to maintain a serum level of above 5ng/mL for 24 hours, as it appears to require 12 hours for the spike in serum β-aescin to reach baseline.[15]



    Aescin Ia is known to be extensively metabolized by lactobacillus brevis and intestinal microflora into various metabolites including Isoaescin Ia, protoaescigenin, desacylescin I, and 21β-O-tigloylprotoaescigenin.[17]

    Aescin Ia is able to convert into Isoaescin Ia in vitro[1] and in the rat, and while the reverse reaction may also occur it is at a lower rate.[14]



    Aescin Ia and Isoaescin Ia appear to have a half-life in the 6-8 hour range.[14][1]



    β-aescin has been confirmed to increase the sensitivity of cells to calcium permeability which seems to apply to all tested cells including cardiac cells,[18] bronciol cells,[19] neurons,[20] skeletal muscle cells.[21][22]


    Cardiovascular Health



    In endothelial cells subject to hypoxia (lack of oxygen), the expected decrease in cellular ATP concentrations and the increase in phospholipase A2 activity appears to be attenuated with 100ng/mL (88nM) aescin, with maximal effects at 750ng/mL (660nM).[23] 250ng/mL aescin (220nM) is also effective in reducing a hypoxia-induced immune cell adherence to the endothelium.[24]

    The adverse effects of hypoxia (lack of oxygen) on blood vessel cells appears to be reduced when there is aescin circulating around the cell at the time of hypoxia

    While aescin does not inherently modify the relaxing effects of acetylcholine on the endothelium, the impairment seen with pyrogallol is reversed in a manner that is again prevented by L-NAME (aescin was unable to preserve relaxation in the presence of pyrogallol and L-NAME).[25] As pyrogallol produces superoxide radicals and reduces nitric oxide bioavailability[26] while L-NAME outright prevents synthesis,[27] these protective effects may be secondary to preserving nitric oxide, which is common for antioxidants (which horse chestnut has been implicated in previously[28]).

    Aescin appears to stimulate nitric oxide production from the endothelium in vitro at 1µM[25] and it has been hypothesized[27] that the increased endothelial cell permeability to calcium seen with aescin[19] can cause an increase in endothelial nitric oxide synthase (eNOS) activity, since eNOS is a calcium dependent enzyme.[29]

    Aescin may be able to sensitize endothelial cells to calcium influx, which results in an increase in nitric oxide production

    Aescin does not modify contractile responses by adrenaline[25] although aescin itself appears to be capable of contracting rabbit portal veins[30] as well as dog[28] and human[31][32] saphenous veins, and the potency in humans appears to be a variable EC50 in the 10-30µM range.[31][32] Although the magnitude of contraction at maximal efficacy is comparable to 100nM adrenaline,[25] the concentrations may be too high to be relevant to oral supplementation.

    Aescin has the potential to increase blood pressure, but this requires concentrations in the blood which are orders of magnitude greater than what is seen in the blood with supplementation of Horse chestnut; this information likely does not apply to supplementation in humans

    Aescin appears to induce PGF2α, an arachidonic acid prostaglandin.[33][30]


    Chronic Venous Insufficiency

    Chronic venous insufficiency (CVI) is a condition where the veins are unable to adequately pump blood back to the heart, which tends to result in itching and discoloration as well as edema of the legs.[34][35] Chronic venous insufficiency is the condition which varicose veins are associated with,[36] and CVI is both an aesthetic and medical complication.

    Studies that assess the efficacy of horse chestnut extract against placebo note that it is significantly more effective when taken over a period of 1-3 months in reducing symptoms of chronic leg insufficiency.[37][38][39][40] While there appear to be significantly more trials in existence according to meta-analysis,[41] they are not available online due to being conducted in German. Said meta-analysis was able to assess 17 trials conducted on horse chestnut extract for the treatment of chronic venous insufficiency and noted significant reductions in leg pain, edema, leg volume (32.10mL with a 95% CI of 13.49-50.72mL) and both ankle (4.71mm with a 95% CI of 1.13-8.28mm) and calf (3.51mm with a 95% CI of 0.58-6.45mm) width as well as itching relative to placebo.[41]

    Relative to placebo, horse chestnut extract at the standard oral doses appears to be effective in reducing all symptoms of chronic venous insufficiency

    Supplementation of a seed extract containing 50mg aescin twice daily for 12 weeks in persons with chronic venous insufficiency noted that supplementation was associated a greater reduction in edema relative to placebo (9.8mL in placebo, 43.8mL with the supplement)[38] yet was a potency comparable to compression therapy (stockings or wraps to physically compress the legs[42]). Other comparative studies have noted that horse chestnut (600mg) is less effective than pycnogenol (360mg) in reducing overall symptoms and leg volume[43] and relative to O-ß-hydroxyethyl rutosides (synthetic analogies of rutin for the usage of chronic venous insufficiency[44]) they appear to be comparable according to reviews[41][45] (both trials conducted in German and not available online).

    Based on limited evidence, the potency of horse chestnut extract for the treatment of chronic venous insufficency appears to be comparable or lesser than pycnogenol and comparable to compression therapy


    Inflammation and Immunology



    It has been noted that while the antiinflammatory effects of aescin are dependent on the adrenal glands, supplementation does not inhernetly increase circulating corticosterone levels.[46] This led to the hypothesis that aescin is enhancing the effects of already present glucocorticoids[47] as the mechanisms attributed to aescin (Phospholipase A2 suppression,[23] NF-kB inhibition,[48] and reduction of cell adhesion factors[49]) are also seen with glucocorticoids.[50][51][52]

    In vitro, aescin and corticosterone can both inhibit macrophage activation (3ng/mL for corticosterone and 10µg/mL for aescin) while the combination appears to be synergistic, reducing secretion of nitric oxide (34.8%), TNF-α (24%), and IL-1β (46.7%) at concentrations of 1ng/mL (corticosterone) and 100ng/mL (aescin).[53]

    2mg/kg aescin injected three hours after inflammation was induced in rats (carrageenan) appears to be insufficient to reduce inflammation, and while 1mg/kg corticosterone was also ineffective the combination reduced edema caused by the inflammation by 52.86%[53] and the combination has been used elsewhere synergistically in rats experiencing retinal barrier breakdown (a consequence of inflammation).[54]

    Aescin appears to have antiinflammatory properties, and while they are inhernetly weak they appear to be able to enhance the antiinflammatory effects of corticosteroids at reasonable concentrations. This is likely relevant to oral supplementation



    Type I hypersensitivities (allergic rhinitis, allergic conjunctivitis, allergic asthma, food allergies and anaphylaxis) are immune responses mostly mediated by mast cells and eosinophils where IgE binding to the FcεRI receptor causes a fairly rapid immune responses;[55][56][57] it is divided into an early phase (IgE binding to FcεRI) and a later phase (mediated by the cytokines released from the mast cells, which are degraded after the early phase) and these inflammatory responses (called allergies) tend to be treated with corticosteroids, anti-histamines and mast cell stabilizers.

    In a passive cutaneous anaphylaxis model (type I hypersensitivity model for the early phase[58]) and ovalbumin-induced airway inflammation (late phase[59]), intraperitoneal injections of β-Aescin (1.5-3mg/kg) is as effective as the reference drug of 3mg/kg dexamethasone in reducing allergic skin responses while it is slightly less effective at reducing lymphocyte infiltration of the lungs.[11] Anti-allergic effects have been noted elsewhere against compound 48/80 with oral aescin.[60]

    β-Aescin appears to have potent anti-allergic effects, and is effective following oral ingestion. While injections are equally effective as corticosteroids, this relative potency may not accurately reflect oral supplementation (since β-Aescin is poorly absorbed)


    Interactions with Organ Systems



    In conditions of circulatory insufficiency in the ears (inner ear disturbances), supplementation of 25mg aescin (although confounded with 450mg troxerutin) five times daily for six weeks was associated with significant improvements in hearing and outperformed the reference drug of 600mg pentoxifylline.[61]

    Thought to be beneficial for inner ear disorders as they are related to poor blood flow in veins, but the only study is confounded with another agent



    The treatment of hemorrhoids is one of the traditionally recommended uses of horse chestnut, mainly as they are congestion of of veins around the anal canal and horse chestnut is known to alleviate congestion of veins.[4]

    It has been reported (via a review,[4] primary text here[62]) that two months supplementation of a thrice daily 40mg aescin supplement was associated with significant improvements in endoscopic evaluation, symptoms, and bleeding (82% response with the supplement relative to 32% in placebo) with benefits within a week of supplement usage.

    Horse chestnut is traditionally recommended for hemorrhoids. While there is not a lot of evidence actually looking into this issue, the lone study noted significant benefits associated with supplementation


    Interactions with Aesthetics



    A side-effect of chronic veinous insufficient (of which horse chestnut is seen as therapeutic) is varicose veins, and thus the usage of horse chestnut is sometimes recommended for varicose veins[4][63] due to the aescin content.[25]

    One study (mentioned in a review[64] and not accessible online) that used oral therapy of 20mg aescin thrice daily in addition to topical application of 4.4mL cream (2% aescin) over eight weeks reported improvements in leg blueness, size, and edema relative to placebo.

    Due to its role in chronic venous insufficiency, horse chestnut supplementation is thought to help with varicose veins (which are a common side-effect during mid to late disease stage); very limited evidence on the topic, but it suggests that it is effective


    Safety and Toxicology



    The meta-analysis on chronic venous insufficiency (2006 version)[41] noted that the most commonly reported side-effects associated with horse chestnut consumption were gastrointestinal complaints, dizziness, nausea, headache, and pruritis. Usually, these side-effects did not differ from placebo (aside from gastrointestinal compliants which sometimes were significant).[41]

    Short term usage of horse chestnut extract is thought to be generally safe, although there may be more gastrointestinal side-effects assocaited with horse chestnut relative to placebo


    Case studies

    The component aesculetin is thought to be present in sufficient quantities to adversely interact with warfarin in regards to blood thinning.[65]

    Due to the anticoagulating effects of aesculetin and the blood flow enhancement with aescins, it is thought that horse chestnut can potentially interact (adversely) with pharamceutical blood thinners such as Warfarin

    In a person with angiomyolipoma (renal tumor thought to be present in 0.13%[66] of the population) which is known to be predisposed to aneurysm and hemorrhage,[67] the usage of an over-the-counter horse chestnut extract was thought to contribute to an observed rupture of said angiomyolipoma.[68]

    A case study has associated horse chestnut extract with a rupture of a form of renal tumor; causation was not placed and this topic is not well explored as it applies to horse chestnut extract

    The β-aescin component has been implicated in instances of contact urticaria (skin hives associated with itching and reddening)[69] and occupational asthma,[70] suggesting that it may be an allergin.

    It appears to be possible to be allergic to β-aescin


    1. ^Sirtori CRAescin: pharmacology, pharmacokinetics and therapeutic profilePharmacol Res.(2001 Sep)
    2. ^Dudek-Makuch M, Matławska ICoumarins in horse chestnut flowers: isolation and quantification by UPLC methodActa Pol Pharm.(2013 May-Jun)
    3. ^Zlatanov MD, Antova GA, Angelova-Romova MJ, Teneva OTLipid composition of Castanea sativa Mill. and Aesculus hippocastanum fruit oilsJ Sci Food Agric.(2013 Feb)
    4. ^[No authors listedAesculus hippocastanum (Horse chestnut). MonographAltern Med Rev.(2009 Sep)
    5. ^Kapusta I, Janda B, Szajwaj B, Stochmal A, Piacente S, Pizza C, Franceschi F, Franz C, Oleszek WFlavonoids in horse chestnut (Aesculus hippocastanum) seeds and powdered waste water byproductsJ Agric Food Chem.(2007 Oct 17)
    6. ^Hübner G, Wray V, Nahrstedt AFlavonol oligosaccharides from the seeds of Aesculus hippocastanumPlanta Med.(1999 Oct)
    7. ^Dudek-Makuch M, Matławska IFlavonoids from the flowers of Aesculus hippocastanumActa Pol Pharm.(2011 May-Jun)
    8. ^Chemical investigation of the New England horse chestnut, aesculus hippocastanum
    9. ^Analysis of sterol fractions from twenty vegetable oils
    10. ^Composition of the sterol fraction in horse chestnut
    11. ^Lindner I, Meier C, Url A, Unger H, Grassauer A, Prieschl-Grassauer E, Doerfler PBeta-escin has potent anti-allergic efficacy and reduces allergic airway inflammationBMC Immunol.(2010 May 21)
    12. ^Di Pierro F, Spinelli G, Monsù G, Alvisi G, Bacci G, Baiocchi C, Buratta M, Martinoli A, Vitali F, Agrifoglio C, Gennaioli F, Lucarelli MClinical effectiveness of a highly standardized and bioavailable mixture of flavonoids and triterpenes in the management of acute hemorroidal crisisActa Biomed.(2011 Apr)
    13. ^Lang W, Mennicke WHPharmacokinetic studies on triatiated aescin in the mouse and ratArzneimittelforschung.(1972 Nov)
    14. ^Wu XJ, Zhang ML, Cui XY, Gao F, He Q, Li XJ, Zhang JW, Fawcett JP, Gu JKComparative pharmacokinetics and bioavailability of escin Ia and isoescin Ia after administration of escin and of pure escin Ia and isoescin Ia in ratJ Ethnopharmacol.(2012 Jan 6)
    15. ^Bässler D, Okpanyi S, Schrödter A, Loew D, Schürer M, Schulz HUBioavailability of beta-aescin from horse chestnut seed extract: comparative clinical studies of two Galenic formulationsAdv Ther.(2003 Sep-Oct)
    16. ^Loew D, Schrödter A, Schwankl W, März RWMeasurement of the bioavailability of aescin-containing extractsMethods Find Exp Clin Pharmacol.(2000 Sep)
    17. ^Yang XW, Zhao J, Cui JR, Guo WStudies on the biotransformation of escin Ia by human intestinal bacteria and the anti-tumor activities of desacylescin IBeijing Da Xue Xue Bao.(2004 Feb)
    18. ^Charles SM, Zhang L, Cipolla MJ, Buchholz JN, Pearce WJRoles of cytosolic Ca2+ concentration and myofilament Ca2+ sensitization in age-dependent cerebrovascular myogenic toneAm J Physiol Heart Circ Physiol.(2010 Oct)
    19. ^Savineau JP, Marthan RActivation properties of chemically skinned fibres from human isolated bronchial smooth muscleJ Physiol.(1994 Feb 1)
    20. ^Fernandez SF, Huang MH, Davidson BA, Knight PR 3rd, Izzo JL JrMechanisms of angiotensin II-mediated decreases in intraneuronal Ca2+ in calcium-loaded stellate ganglion neuronsHypertension.(2005 Feb)
    21. ^Ikemoto T, Iino M, Endo MEnhancing effect of calmodulin on Ca(2+)-induced Ca2+ release in the sarcoplasmic reticulum of rabbit skeletal muscle fibresJ Physiol.(1995 Sep 15)
    22. ^Launikonis BS, Stephenson DGEffects of beta-escin and saponin on the transverse-tubular system and sarcoplasmic reticulum membranes of rat and toad skeletal musclePflugers Arch.(1999 May)
    23. ^Arnould T, Janssens D, Michiels C, Remacle JEffect of aescine on hypoxia-induced activation of human endothelial cellsEur J Pharmacol.(1996 Nov 14)
    24. ^Bougelet C, Roland IH, Ninane N, Arnould T, Remacle J, Michiels CEffect of aescine on hypoxia-induced neutrophil adherence to umbilical vein endotheliumEur J Pharmacol.(1998 Mar 12)
    25. ^Carrasco OF, Vidrio HEndothelium protectant and contractile effects of the antivaricose principle escin in rat aortaVascul Pharmacol.(2007 Jul)
    26. ^Moncada S, Palmer RM, Gryglewski RJMechanism of action of some inhibitors of endothelium-derived relaxing factorProc Natl Acad Sci U S A.(1986 Dec)
    27. ^Pierrakos CN, Tsolakis EJ, Pozios IA, Diakos N, Charitos E, Malliaras K, Bonios MJ, Lazaris N, Papazoglou P, Venetsanakos J, Papalois A, Terrovitis JV, Nanas JNEffects of l-NAME on coronary blood flow, infarct size and the extent of the no-reflow phenomenonInt J Cardiol.(2012 Sep 27)
    28. ^Guillaume M, Padioleau FVeinotonic effect, vascular protection, antiinflammatory and free radical scavenging properties of horse chestnut extractArzneimittelforschung.(1994 Jan)
    29. ^Alderton WK, Cooper CE, Knowles RGNitric oxide synthases: structure, function and inhibitionBiochem J.(2001 Aug 1)
    30. ^Berti F, Omini C, Longiave DThe mode of action of aescin and the release of prostaglandinsProstaglandins.(1977 Aug)
    31. ^Annoni F, Mauri A, Marincola F, Resele LFVenotonic activity of escin on the human saphenous veinArzneimittelforschung.(1979)
    32. ^Responsiveness of human varicose saphenous veins to vasoactive agents
    33. ^Longiave D, Omini C, Nicosia S, Berti FThe mode of action of aescin on isolated veins: relationship with PGF2 alphaPharmacol Res Commun.(1978 Feb)
    34. ^Smith PCThe causes of skin damage and leg ulceration in chronic venous diseaseInt J Low Extrem Wounds.(2006 Sep)
    35. ^Beebe-Dimmer JL, Pfeifer JR, Engle JS, Schottenfeld DThe epidemiology of chronic venous insufficiency and varicose veinsAnn Epidemiol.(2005 Mar)
    36. ^Partsch HVaricose veins and chronic venous insufficiencyVasa.(2009 Nov)
    37. ^Diehm C, Vollbrecht D, Amendt K, Comberg HUMedical edema protection--clinical benefit in patients with chronic deep vein incompetence. A placebo controlled double blind studyVasa.(1992)
    38. ^Diehm C, Trampisch HJ, Lange S, Schmidt CComparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiencyLancet.(1996 Feb 3)
    39. ^Friederich HC, Vogelsberg H, Neiss AEvaluation of internally effective venous drugsZ Hautkr.(1978 Jun 1)
    40. ^Neiss A, Böhm CDemonstration of the effectiveness of the horse-chestnut-seed extract in the varicose syndrome complexMMW Munch Med Wochenschr.(1976 Feb 13)
    41. ^Pittler MH, Ernst EHorse chestnut seed extract for chronic venous insufficiencyCochrane Database Syst Rev.(2006 Jan 25)
    42. ^Partsch HCompression therapy of the legs. A reviewJ Dermatol Surg Oncol.(1991 Oct)
    43. ^Koch RComparative study of Venostasin and Pycnogenol in chronic venous insufficiencyPhytother Res.(2002 Mar)
    44. ^Belcaro G, Rosaria Cesarone M, Ledda A, Cacchio M, Ruffini I, Ricci A, Ippolito E, Di Renzo A, Dugall M, Corsi M, Marino Santarelli AR, Grossi MGO-(beta-hydroxyethyl)-rutosides systemic and local treatment in chronic venous disease and microangiopathy: an independent prospective comparative studyAngiology.(2008 Feb-Mar)
    45. ^Wadworth AN, Faulds DHydroxyethylrutosides. A review of its pharmacology, and therapeutic efficacy in venous insufficiency and related disordersDrugs.(1992 Dec)
    46. ^Hiai S, Yokoyama H, Oura HEffect of escin on adrenocorticotropin and corticosterone levels in rat plasmaChem Pharm Bull (Tokyo).(1981 Feb)
    47. ^Escin may exert a synergistic anti-inflammatory effect with glucocorticoids
    48. ^Xiao GM, Wei JEffects of beta-Aescin on the expression of nuclear factor-kappaB and tumor necrosis factor-alpha after traumatic brain injury in ratsJ Zhejiang Univ Sci B.(2005 Jan)
    49. ^Hu XM, Zhang Y, Zeng FDEffects of sodium beta-aescin on expression of adhesion molecules and migration of neutrophils after middle cerebral artery occlusion in ratsActa Pharmacol Sin.(2004 Jul)
    50. ^Cytoplasmic phospholipase A2 activity and gene expression are stimulated by tumor necrosis factor: dexamethasone blocks the induced synthesis
    51. ^Auphan N, DiDonato JA, Rosette C, Helmberg A, Karin MImmunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesisScience.(1995 Oct 13)
    52. ^A mechanism for the antiinflammatory effects of corticosteroids: The glucocorticoid receptor regulates leukocyte adhesion to endothelial cells and expression of endothelial-leukocyte adhesion molecule 1 and intercellular adhesion molecule 1
    53. ^Xin W, Zhang L, Sun F, Jiang N, Fan H, Wang T, Li Z, He J, Fu FEscin exerts synergistic anti-inflammatory effects with low doses of glucocorticoids in vivo and in vitroPhytomedicine.(2011 Feb 15)
    54. ^Zhang F, Li Y, Zhang L, Mu GSynergistic protective effects of escin and low‑dose glucocorticoids on blood‑retinal barrier breakdown in a rat model of retinal ischemiaMol Med Rep.(2013 May)
    55. ^Deciphering New Molecular Mechanisms of Mast Cell Activation
    56. ^Bloemen K, Verstraelen S, Van Den Heuvel R, Witters H, Nelissen I, Schoeters GThe allergic cascade: review of the most important molecules in the asthmatic lungImmunol Lett.(2007 Oct 31)
    57. ^Marshall JSMast-cell responses to pathogensNat Rev Immunol.(2004 Oct)
    58. ^Inagaki N, Nagai HAnalysis of the mechanism for the development of allergic skin inflammation and the application for its treatment:mouse models for the development of remedies for human allergic dermatitisJ Pharmacol Sci.(2009 Jul)
    59. ^Shum BO, Rolph MS, Sewell WAMechanisms in allergic airway inflammation - lessons from studies in the mouseExpert Rev Mol Med.(2008 May 27)
    60. ^Sipos W, Reutterer B, Frank M, Unger H, Grassauer A, Prieschl-Grassauer E, Doerfler PEscin inhibits type I allergic dermatitis in a novel porcine modelInt Arch Allergy Immunol.(2013)
    61. ^Siegers CP, Syed Ali S, Tegtmeier MAescin and troxerutin as a successful combination for the treatment of inner ear perfusion disturbancesPhytomedicine.(2008 Mar)
    62. ^Pirard J, Gillet P, Guffens JM, Defrance PDouble blind study of reparil in proctologyRev Med Liege.(1976 May 15)
    63. ^MacKay DHemorrhoids and varicose veins: a review of treatment optionsAltern Med Rev.(2001 Apr)
    64. ^Suter A, Bommer S, Rechner JTreatment of patients with venous insufficiency with fresh plant horse chestnut seed extract: a review of 5 clinical studiesAdv Ther.(2006 Jan-Feb)
    65. ^Heck AM, DeWitt BA, Lukes ALPotential interactions between alternative therapies and warfarinAm J Health Syst Pharm.(2000 Jul 1)
    66. ^Fujii Y, Ajima J, Oka K, Tosaka A, Takehara YBenign renal tumors detected among healthy adults by abdominal ultrasonographyEur Urol.(1995)
    67. ^Eble JNAngiomyolipoma of kidneySemin Diagn Pathol.(1998 Feb)
    68. ^Snow A, Halpenny D, McNeill G, Torreggiani WCLife-threatening rupture of a renal angiomyolipoma in a patient taking over-the-counter horse chestnut seed extractJ Emerg Med.(2012 Dec)
    69. ^Escribano MM, Muñoz-Bellido FJ, Velázquez E, Delgado J, Serrano P, Guardia J, Condé JContact urticaria due to aescinContact Dermatitis.(1997 Nov)
    70. ^Muñoz X, Culebras M, Cruz MJ, Morell FOccupational asthma related to aescin inhalationAnn Allergy Asthma Immunol.(2006 Mar)