The Chemistry and Bioactivity of Eucommia ulmoides Oliver Leaves

Chemistry Eucommia ulmoides Oliver is a single species of the genus Eucommia which is the only genus in the family Eucommiaceae. The bark has been traditionally used in analgesics, tonics, and hypotensives in China. Moreover, the Chinese medical book “Bencao gangmu” describes fresh Eucommia leaf (EL) as being “consumed as a vegetable.” The product “Tochu-cha,” which is available in the Japanese markets and used in beverages, is roasted EL containing the iridoid glycosides: geniposidic acid and asperuloside, and a caffeic acid derivative: chlorogenic acid as its major ingredients. Eight iridoids, together with 14 known compounds were isolated from Eucommia leaf extract (ELE). The detailed investigation of the constituents of Eucommia green leaf powder (EGLP) led to the isolation of six iridoids, five flavonoids, and chlorogenic acid. Three additional new iridoids were obtained, two of which (eucomoside B and eucomoside C) were isolated by the condensation of geniposidic acid and amino acids (phenylalanine and tryptophan, respectively), whereas the third (eucomoside A) was determined to be an acetal compound with a linkage from C-3 of the iridoid to C-2 of the glucose unit, each being the first such natural compound described. Bioactivities Spontaneously hypertensive rats fed ELE exhibited a dose-dependent antihypertensive effect. Moreover, follow-up studies have confirmed that ELE decreases systolic blood pressure in humans after long-term intake. These antihypertensive effects are presumed to be due to the activity of a so-called EL glycoside, which contains geniposidic acid as a major component. The extract from ELs containing EL glycoside is used as the food supplement in the food for specified health uses (FOSHU). Metabolic syndrome (MS)-like rats fed ELE or EGLP exhibited dose-dependent antiobesity and anti-MS effects. Both forms of ELs minimized increases in body weight and visceral fat in a dose-dependent manner. Concomitantly, an increase in plasma adiponectin levels and a suppression of plasma resistin and tumor necrosis factor α levels were demonstrated. The chronic administration of asperuloside isolated from ELs suppressed increases in body weight, white adipose tissue (WAT) weight, plasma triglyceride levels, and free fatty acid levels in a mouse model. Further, the chronic administration of asperuloside enhanced the basal metabolic rate in rats fed a high-fat diet (HFD) and significantly decreased respiratory quotientsmore than that in the HFD control group, suggesting an acceleration of lipid metabolism. Real-time PCR studies showed that ELE and asperuloside enhanced metabolic function in several organs, including the diminution of adenosine 5′-triphosphate production in WAT, the acceleration of β-oxidation in the liver, and an increase in the use of ketone bodies/glucose in skeletal muscle, all of which may exert antiobesity effects under HFD conditions due to novel mechanisms. To our knowledge, this is the first study showing the antiobesity effects of iridoid asperuloside. These findings are expected to result in new health applications of EL and the development of EL as a FOSHU.