World Botanical Associates Web Page
Prepared by Richard W. Spjut
Aesculus californica (Calothyrsus californica Spach 1834) Nuttall 1838. California buckeye. Usually a tree from 512 m with a broad hemispherical crown; leaves deciduous, opposite, compound, divided digitately into 57 serrated somewhat sword-shaped leaflets. Flowering MayJul; flowers aggregated into a long cylindrical to pyramidal mass on a flowering axis above the leafy stems; petals white to pale rose, stamens orange; fruit (capsule) persistent, developing from a three-parted (loculed) ovary, each part with two ovules, but few mature to seed; at maturity capsule opening along one to several sutures; seeds large, reddish brown to pale orange. A common tree in California mixed conifer and broadleaf forests in the northern Coast Ranges and along the west slopes of the Sierra Nevada; in Kern Co., a characteristic tree of the vegetation in Kern Canyon associated with ghost pine and Douglas oak on the steep open slopes above the Kern River. Flowers and seeds have been used by native Indians to stupefy fish. Contains saponins.
Carrasco O. F. and H. Vidrio. 2007. Endothelium protectant and contractile effects of the antivaricose principle escin in rat aorta. Vascul. Pharmacol. 47(1): 6873. The triterpene saponin escin is the active component of the extract of seeds of Aesculus hippocastanum used in the treatment of chronic venous insufficiency. Escin is also used experimentally to increase membrane permeability in isolated cells. Since endothelial dysfunction is postulated to be involved in venous insufficiency, the possible endothelium-protectant effect of escin was explored in rat aortic rings, a model widely used to study such effects with cardiovascular agents. Escin enhanced endothelium-dependent relaxation induced by acetylcholine when such relaxation had been reduced by exposure to the superoxide ion generator pyrogallol. This effect was attributed to enhanced nitric oxide production by endothelial nitric oxide synthase, a calcium-dependent enzyme, activated by the increased endothelial cell permeability to calcium induced by escin. Another effect of escin thought to contribute to its therapeutic activity is its ability to produce venous contraction. The compound was found to induce concentration-related contraction also in rat aortic rings. This response was partially inhibited by removal of the endothelium or by preincubation with indomethacin, and was completely abolished by incubation in a calcium-free perfusion fluid. Contraction was considered to be due mainly to the aforementioned effect on calcium permeability, with some mediation by release of endothelial vasoconstrictor prostanoids. It was concluded that, in rat aorta, escin possesses an endothelium-protectant action and a direct contractile effect. The former could contribute to its beneficial effect in the treatment of venous insufficiency, while the latter could constitute a limiting side effect.
Dickson S., J. Gallagher, L. McIntyre, A. Suter and J. Tan. 2004. An open study to assess the safety and efficacy of Aesculus hippocastanum tablets (Aesculaforce 50mg) in the treatment of chronic venous insufficiency. J. Herb. Pharmacother. 4(2): 1932. An open study was carried out to assess, primarily, the safety and tolerability of Aesculus hippocastanum in the treatment of CVI. Patients underwent 8 consecutive weeks of treatment and were asked to take one 50 mg Aesculus hippocastanum tablet, twice daily. In total, 91 adverse events were reported, of which only 4 were rated as probably related to the study drug. Patients judged the tolerability of the study medication in the majority of the cases at visits 2 and 3 (90 and 95%, respectively) to be "good" or "fairly good." Only 2 patients rated tolerability as poor at visit 3. For each of the symptoms investigated the difference in the median value between baseline and visit 3 was found to be statistically significant and both the ankle and lower leg circumference decreased. The PPG measurements were rejected after analysis since validation measurements carried out after the trial showed that the PPG technique had an internal error of around 30%. Nevertheless, the majority of patients rated efficacy to be "very good" or "good," with only 10 patients reporting no effect by the end of the study. The results of this study indicate that Aesculaforce 50 mg tablets are a safe, well-tolerated and efficacious treatment for Widmer stage I and II CVI.
Konoshima T and K. H. Lee. 1986. Antitumor agents, 82. Cytotoxic sapogenols from Aesculus hippocastanum. J. Nat. Prod. 49(4): 650656.
MacKay D. 2001. Hemorrhoids and varicose veins: a review of treatment options. Altern. Med. Rev. 6(2):126140. Hemorrhoids and varicose veins are common conditions seen by general practitioners. Both conditions have several treatment modalities for the physician to choose from. Varicose veins are treated with mechanical compression stockings. There are several over-the-counter topical agents available for hemorrhoids. Conservative therapies for both conditions include diet, lifestyle changes, and hydrotherapy which require a high degree of patient compliance to be effective. When conservative hemorrhoid therapy is ineffective, many physicians may choose other non-surgical modalities: injection sclerotherapy, cryotherapy, manual dilation of the anus, infrared photocoagulation, bipolar diathermy, direct current electrocoagulation, or rubber band ligation. Injection sclerotherapy is the non-surgical treatment for primary varicose veins. Non-surgical modalities require physicians to be specially trained, own specialized equipment, and assume associated risks. If a non-surgical approach fails, the patient is often referred to a surgeon. The costly and uncomfortable nature of treatment options often lead a patient to postpone evaluation until aggressive intervention is necessary. Oral dietary supplementation is an attractive addition to the traditional treatment of hemorrhoids and varicose veins. The loss of vascular integrity is associated with the pathogenesis of both hemorrhoids and varicose veins. Several botanical extracts have been shown to improve microcirculation, capillary flow, and vascular tone, and to strengthen the connective tissue of the perivascular amorphous substrate. Oral supplementation with Aesculus hippocastanum, Ruscus aculeatus, Centella asiatica, Hamamelis virginiana, and bioflavonoids may prevent time-consuming, painful, and expensive complications of varicose veins and hemorrhoids.
Matsuda H., Y. Li, T. Murakami, K. Ninomiya, J. Yamahara and M. Yoshikawa. 1997. Effects of escins Ia, Ib, IIa, and IIb from horse chestnut, the seeds of Aesculus hippocastanum L., on acute inflammation in animals. Biol. Pharm. Bull 20(10): 10921095. We investigated the effects of escins Ia, Ib, and IIb isolated from horse chestnut, the seeds of Aesculus hippocastanum L., and desacylescins I and II obtained by alkaline hydrolysis of escins on acute inflammation in animals (p.o.). Escins Ia, Ib, IIa, and IIb (50-200 mg/kg) inhibited the increase of vascular permeability induced by both acetic acid in mice and histamine in rats. Escins Ib, IIa, and IIb (50-200 mg/kg) also inhibited that induced by serotonin in rats, but escin Ia didn't. Escins Ia, Ib, IIa, and IIb (200 mg/kg) inhibited the hind paw edema induced by carrageenin at the first phase in rats. Escin Ia (200 mg/kg) and escins Ib, IIa, and IIb (50-200 mg/kg) inhibited the scratching behavior induced by compound 48/80 in mice, but escin Ia was weakest. Desacylescins I and II (200 mg/kg) showed no effect. With regard to the relationship between their chemical structures and activities, the acyl groups in escins were essential. Escins Ib, IIa, and IIb with either the 21-angeloyl group or the 2'-O-xylopyranosyl moiety showed more potent activities than escin Ia which had both the 21-tigloyl group and the 2'-O-glucopyranosyl moiety.
Popp W, F. Horak, S. Jager, K. Reiser, C. Wagner and H. Zwick. 1992. Horse chestnut (Aesculus hippocastanum) pollen: a frequent cause of allergic sensitization in urban children. Allergy 47(4 Pt 2): 380383. We investigated the incidence of allergic sensitization and the risk factors underlying sensitization in 214 urban children exposed to horse chestnut pollen. By means of the Phadezym RAST, we found IgE specific to horse chestnut pollen in 12.6% of the urban children, whereas it occurred in only 1.9% of control subjects recruited from a rural area. Reports of allergic symptoms in spring during the horse chestnut pollen load coincided with the presence of specific IgE in 5.1% of the urban group as against 1.4% of the recruited from the rural area. Environmental factors other than those related to urban living and higher horse chestnut pollen counts had no significant impact on allergic sensitization. Increased total IgE levels (greater than 100 kU/l), however, and the sensitization to pollen of other species significantly raised the odds for sensitization to chestnut pollen. They were highest in highly atopic children with sensitization to pollen, especially to that of plane trees (OR = 73.9). These results suggest the relevance of horse chestnut pollen because of the high allergic sensitization rate among urban children, and they should also be borne in mind when it comes to the planting of trees in urban areas.
Sakurai T., T. Nishimura, N. Otake, Y. Xinsheng, K. Abe, M. Zeida, H. Nagasawa and S. Sakuda. 2002. Assamicin I and II, novel triterpenoid saponins with insulin-like activity from Aesculus assamica Griff. Bioorg. Med. Chem. Lett. 12(5): 807810. Two novel triterpenoid saponins with insulin-like activity, termed assamicin I and II, were isolated from the roots of Aesculus assamica Griff. and their structures were characterized as 1 and 2, respectively. They inhibited release of free fatty acids from epinephrine-treated rat adipocytes and enhanced glucose uptake into 3T3-L1 adipocytes.
Suter A, S. Bommer S and J. Rechner. 2006. Treatment of patients with venous insufficiency with fresh plant horse chestnut seed extract: a review of 5 clinical studies. Adv. Ther. 23(1): 179190. Extracts from the seed of the horse chestnut (Aesculus hippocastanum L.) have traditionally been used to treat patients with chronic venous insufficiency and to alleviate its associated symptoms, including lower leg swelling. The efficacy of preparations that contain horse chestnut seed extract (HCSE) is believed to be due largely to an inhibitory effect on the catalytic breakdown of capillary wall proteoglycans. Aesculaforce is a fresh plant HCSE that is available as an oral tincture, as tablets (20 mg or 50 mg), and as topical gel. Four clinical trials in patients with chronic venous insufficiency and 1 study in patients with varicose veins demonstrated the effectiveness of these preparations through the objective measure of reduction in lower leg edema and the subjective alleviation of leg pain, heaviness, and itching. Safe, well tolerated, and acceptable to patients, the fresh plant HCSE preparation Aesculaforce offers a real alternative in the treatment of patients with mild to moderate venous insufficiency.
Williams M. C. and J. D. Olsen. 1984. Toxicity of seeds of three Aesculus spp to chicks and hamsters. Am. J. Vet. Res. 45(3): 539542. Seeds of horse chestnut (Aesculus hippocastanum), Ohio buckeye (A glabra), and yellow buckeye (A octandra) were tested for toxicity to 2-week-old Leghorn chicks and adult female Syrian hamsters. The LD50 of the water soluble portion of alcoholic extracts of horse-chestnut seeds (for hamsters and chicks) and of dried, powdered seeds (chicks only) was determined. The LD50 for a single dose of extract from horse-chestnut seeds was 10.6 mg/g of body weight for chicks and 10.7 mg/g of body weight for hamsters. The LD50 for chicks given 2 consecutive daily doses of horse-chestnut seed was 6.5 mg/g. Toxic signs included depression, muscular incoordination, paralysis, coma, and death. Extracts of seeds of Ohio buckeye were nontoxic to chicks and hamsters when fed at 80 mg/g. One of 5 hamsters died after dosing for 5 days with 80 mg/g of extract of seeds of yellow buckeye/g.
Wei F., S. C. Ma, L. Y. Ma, P. P. But, R. R. Lin and I. A. Khan. 2004. Antiviral flavonoids from the seeds of Aesculus chinensis. J. Nat. Prod. 67(4): 650653. A bioassay-guided fractionation of an ethanol extract of the seeds of Aesculus chinensis led to the isolation of two new flavanoids (1 and 2), along with eight known ones (3-10). The structures of the new compounds were elucidated by spectroscopic methods including 2D NMR. All compounds were tested for antiviral activity against respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV 3), and influenza virus type A (Flu A). Compounds 1, 2, and 6 showed significant antiviral activities against RSV with IC(50) values of 4.5, 6.7, and 4.1 microg/mL and selective index (SI) values of 15.8, 32, and 63.8, respectively. Compound 8 demonstrated significant antiviral activity against Flu A with an IC(50) of 24.5 microg/mL and a SI of 16.0, respectively.
Yang X.W., J. Zhao, C. X. Cui, X. H. Liu, C. M. Ma, M. Hattori and H. Zhang. 1999. Anti-HIV-1 protease triterpenoid saponins from the seeds of Aesculus chinensis. J. Nat. Prod. 62(11): 15101513. Eight bioactive triterpenoid saponins (1-8) were isolated from the seeds of Aesculus chinensis, four of which are novel compounds. The major saponins were identified as escin Ia (1), Ib (2), isoescin Ia (3) and Ib (4), while the new compounds were identified as 22alpha-tigloyl-28-acetylprotoaescigenin-3beta-O- inverted question markbeta -D-glucopyranos yl (1-2) inverted question markbeta-D-glucopyranosyl (1-4)-beta-D-glucopyranosiduronic acid (escin IVc, 5), 22alpha-angeloyl-28-acetylprotoaescigenin-3beta-O- inverted question markbet a-D-glucopyrano syl (1-2) inverted question markbeta-D-glucopyranosyl (1-4)-beta-D-glucopyranosiduronic acid (escin IVd, 6), 28-tigloylprotoaescigenin-3beta-O- inverted question markbeta-D-glucopyranosyl (1-2) inverted question markbeta-D-glucopyranosyl (1-4)-beta-D-glucopyranosiduronic acid (escin IVe, 7), and 28-angeloylprotoaescigenin-3beta-O- inverted question markbeta-D-glucopyranosyl (1-2) inverted question markbeta-D-glucopyranosyl (1-4)-beta-D-glucopyranosiduronic acid (escin IVf, 8). The structures were determined by chemical and spectroscopic methods. All the above compounds were evaluated for their inhibitory activity against HIV-1 protease.
Zhou Y., X. Hui, N. Li, W. Zhuang, G. Liu, T. Wu, M. Wei and X. Wu. 2005. Saponins from Chinese Buckeye Seed reduce cerebral edema: metaanalysis of randomized controlled trials. Planta Med.71(11): 993998. To evaluate the effects of saponins from Chinese Buckeye Seed in the treatment of cerebral edema in patients with stroke or cerebral trauma, a metaanalysis of randomized controlled trials was conducted. Randomized trials that compare the effects of treatment with saponins from Chinese Buckeye Seed to placebo treatment, to lack of treatment, to non-specific treatment, or to mannitol treatment for cerebral edema were identified with electronic and manual searches. No blinding and language limitations were applied. The methodological quality of trials was assessed with the Jadad scale plus allocation concealment. The metaanalysis was performed where data were available. Forty-one randomized controlled trials involving 4066 patients were identified. The methodological quality of the trials was generally low. The combined results showed that intravenous administration of saponins from Chinese Buckeye Seed increased the total effective rate, reduced the mortality and the incidence of renal function impairment in comparison to control treatment. No serious adverse event was reported. Based on the metaanalysis, saponins from Chinese Buckeye Seed can reduce cerebral edema in patients with stroke or cerebral trauma. However, the evidence is not sufficient due to the generally low methodological quality of the studies. Further trials are needed with sufficiently numerous group size and rigorous design.