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Horse Chestnut (Aesculus hippocastanum)

Horse chestnut (Aesculus hippocastanum L.) is a deciduous tree native to parts of southeastern Europe, particularly the Balkan Peninsula, but now cultivated in many areas of Europe and North America. The tree produces fruits that are made up of a spiny capsule containing one to three large seeds, known as horse chestnuts. Traditionally, many of the aerial parts of the horse chestnut tree, including the seeds, leaves, and bark, were used in medicinal preparations. Its fruits contain seeds that resemble sweet chestnuts but have a bitter taste. Modern extracts of horse chestnut are usually made from the seeds, which are high in the active constituent aescin (also known as escin).

Horse Chestnut (Aesculus hippocastanum)

Usos

A number of reports dating from the early 18th century have indicated therapeutic properties for horse chestnut. These have ranged from anti-fever (Bon, 1720) to, at the end of the 19th century, anti-hemorrhoidal properties. Historically, horse chestnut seed extract has also been used for joint pain, bladder and gastrointestinal problems, fever, leg cramps, and other conditions. Today, horse chestnut seed extract is promoted for chronic venous insufficiency (CVI; poor blood flow in the veins of the legs, which may lead to leg pain, swelling, itchiness, and other symptoms), varicose veins, hemorrhoids, phlebitis (inflammation of the veins), diarrhea, fever, enlargement of the prostate gland, rectal complaints, irritable bowel syndrome, male infertility, and other conditions.

Química/Farmacología

Horse chestnut seeds are rich in saponins (3–5%), over thirty of which have been isolated and identified. The main compound is aescin – a mixture of acylated triterpene glycosides. Three fractions of aescin, denoted as crypto-, α-, and β-aescin have been described in the literature. Cryptoaescin contains C-28-O-acetyl saponins, and β-aescin contains C-22-O-acetyl saponins, whereas α-aescin is a mixture of crypto- and β-aescin. β-Aescin (mainly made up of aescin Ia and aescin Ib ) is the major active component of extracts from horse chestnut seeds, whereas α-aescin (made up mainly of isoaescin Ia and isoaescin Ib ) is less bioactive. Horse chestnut seeds also contain flavonoids: quercetin and kaempferol derivatives, proanthocyanidins, sterols, and significant amounts of starch.

Estudios clínicos

A 2012 systematic review of 17 studies suggested that horse chestnut seed extract can improve symptoms of CVI. Results from one of these studies suggested that horse chestnut seed extract may be as effective as wearing compression stockings. Data from earlier trials suggest horse chestnut seed extract has efficacy against chronic venous insufficiency and is safe and well tolerated. Other studies suggest aescin may improve sperm quality in patients with varicocele-associated infertility. Research results have shown that the complete extract has been around 100 times more effective as the treatment for inflammation and lymphoedema in rats than the extract from which aescin was removed.

Mecanismo biomecánico

Saponins

The saponin content of seeds consists of α-aescin and β-aescin, the latter of which is, in turn, composed of more than 30 derivatives of the triterpenoids, protoaescigenin and barringtogenol C. These compounds are primarily found in the seed cotyledons, but have also been detected in the seed integument, the bark, buds, leaves and the immature fruit pericarp of A. hippocastanum.
Aescin has been demonstrated to have potent antiinflammatory effects, especially on the early stages of induced inflammation and can also reduce ethanol absorption and display hypoglycemic actions when taken orally. Aescin also has positive therapeutic effects on the microvasculature and its surrounding connective tissues. Such tissues are composed of cellular and fibrous components in a fluid ‘ground substance’ or extracellular matrix, which consists of proteoglycans and glucosaminoglycans, and provides support and cushioning to blood vessels and fibrous tissues. One of the key components of this ground substance is hyaluronic acid, a proteoglycan, which gives the extracellular matrix its viscosity.

Flavonoids

As a class of phytochemicals, flavonoids are widely accepted as possessing a range of biological activities which may be of relevance in the context of topical application of flavonoid-containing preparations. Several flavonoids (mainly glycoside derivatives of quercetin and kaempferol) have been detected in A. hippocastanum, including astragalin (kaempferol 3-Oglucoside), isoquercitrin (quercetin-3 -glucoside), leucocyanidin (3,3',4,4',5,7 hexahydroxyflavone) and rutin (quercetin 3-rutinoside). In the specific case of horse chestnut flavonoids, rutin has been described as possessing radical scavenging, anti-bacterial and anti-viral activities, and is also used medicinally in the treatment of varicose veins and capillary fragility. These compounds are primarily found in the bark, leaves buds and fruit pericarp, but have also been found in the seed integument. Previously, this latter tissue has been eliminated from extracts used in the preparation of drugs, but, if included, it would provide a valuable additional source of bioactive compounds.

Lab studies suggest that aescin in horse chestnut has anti-inflammatory, neuroprotective, and antitumor effects. Its anti-inflammatory effects involve downregulation of inflammatory gene expression and upregulation granulocyte-macrophage colony-stimulating factor production, which also confers neuroprotection. Aescin reduces the release of enzymes that typically increase with chronic vein diseases. Other compounds in horse chestnut generally improve blood vessel tone. Aescin may reduce chronic venous insufficiency via inhibition of elastase and hyaluronidase, both involved in enzymatic proteoglycan degradation, which constitutes part of the capillary endothelium and is the main component of the extravascular matrix. Contraction of veins and arteries with horse chestnut may be partially mediated through 5-HT(2A) receptors. It also reduced platelet aggregation in vitro.

Fuentes/Artículos

Diehm C, Trampisch HJ, Lange S, Schmidt C. Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency. Lancet. 1996;347:292-4.

Diehm C, Vollbrecht D, Amendt K, Comberg HU. Medical edema protection—clinical benefit in patients with chronic deep vein incompetence. A placebo controlled double blind study. Vasa. 1992;21:188-92.

Dudek-Makuch, Marlena, and Elżbieta Studzińska-Sroka. "Horse chestnut–efficacy and safety in chronic venous insufficiency: an overview." Revista Brasileira de Farmacognosia 25 (2015): 533-541. https://www.scielo.br/j/rbfar/a/yWfdx5FHQCzLLypNL34GVDM/?lang=en&format=html

Edem E, Kahyaoglu B, Cakar MA. Acute Effusive Pericarditis due to Horse Chestnut Consumption. Am J Case Rep. May 4 2016;17:305-308.

Fang Y, Zhao L, Yan F, et al. Escin improves sperm quality in male patients with varicocele-associated infertility. Phytomedicine. 2010 Mar;17(3-4):192-6.

Felixsson E, Persson IA, Eriksson AC, Persson K. Horse chestnut extract contracts bovine vessels and affects human platelet aggregation through 5-HT(2A) receptors: an in vitro study. Phytother Res. 2010 Sep;24(9):1297-301.

Harikumar KB, Sung B, Pandey MK, et al. Escin, a pentacyclic triterpene, chemosensitizes human tumor cells through inhibition of nuclear factor-kappaB signaling pathway. Mol Pharmacol. 2010 May;77(5):818-27.

Huang Y, Zheng SL, Zhu HY, Xu ZS, Xu RA. Effects of aescin on cytochrome P450 enzymes in rats. J Ethnopharmacol. 2014;151(1):583-90.

Methlie, Camilla Borthen, and Jan Schjøtt. "Horse chestnut--remedy for chronic venous insufficiency." Tidsskrift for den Norske Laegeforening: Tidsskrift for Praktisk Medicin, ny Raekke 129, no. 5 (2009): 420-422. https://europepmc.org/article/med/19247403

Ming ZJ, Hu Y, Qiu YH, Cao L, Zhang XG. Synergistic effects of beta-aescin and 5-fluorouracil in human hepatocellular carcinoma SMMC-7721 cells.Phytomedicine. 2010;17(8-9):575-80.

Ottillinger, Bertram, and Karin Greeske. "Rational therapy of chronic venous insufficiency–chances and limits of the therapeutic use of horse-chestnut seeds extract." BMC cardiovascular disorders 1, no. 1 (2001): 1-5. https://bmccardiovascdisord.biomedcentral.com/articles/10.1186/1471-2261-1-5

Pittler MH, Ernst E. Horse chestnut seed extract for chronic venous insufficiency. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003230.

Pittler, Max H., and Edzard Ernst. "Horse chestnut seed extract for chronic venous insufficiency." Cochrane database of systematic reviews 11 (2012). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144685/

Pittler MH, et al.Horse-chestnut seed extract for chronic venous insufficiency. A criteria-based systematic review. Arch Dermatol. 1998;134:1356-60.

Siebert U, Brach M, Sroczynski G, Berla K. Efficacy, routine effectiveness, and safety of horsechestnut seed extract in the treatment of chronic venous insufficiency. A meta-analysis of randomized controlled trials and large observational studies. Int Angiol. 2002 Dec;21(4):305-15.

Sirtori, Cesare R. "Aescin: pharmacology, pharmacokinetics and therapeutic profile." Pharmacological Research 44, no. 3 (2001): 183-193. https://sunwavepharma.com/studii/mse/studiu%201%20endolex%20forte.pdf

Suter, Andy, Silvia Bommer, and Jordan Rechner. "Treatment of patients with venous insufficiency with fresh plant horse chestnut seed extract: a review of 5 clinical studies." Advances in therapy 23, no. 1 (2006): 179-190. https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.603.8014&rep=rep1&type=pdf

Yi HY, Lee JY. Poisoning due to consumption of horse chestnut seed. Clin Exp Emerg Med. Dec 2021;8(4):333-335.

Zhang L, Fu F, Zhang X et al. Escin attenuates cognitive deficits and hippocampal injury after transient global cerebral ischemia in mice via regulating certain inflammatory genes. Neurochem Int. 2010 Sep;57(2):119-27.

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