Oral administration of Eucommia ulmoides Oliv. leaves extract protects against atherosclerosis by improving macrophage function in ApoE knockout mice.

Eucommia leaf extract (ELE) is a traditional Chinese herbal medicine. We investigated the effect of ELE on the development of atherosclerosis and changes in peritoneal macrophage function in apolipoprotein E knockout (ApoE-/- ) mice. At 8 weeks of age, ApoE-/- mice were randomly divided into three groups that were fed a high-fat diet blended with 0% (control), 5% or 10% ELE for a period of 7 weeks. The 10% ELE dose caused an approximately 36% reduction in atherosclerotic lesions, as estimated by oil red O staining. Real-time PCR analysis showed that the 1-week treatment with ELE reduced mRNA levels of Tnf-alpha, Il-1, and Mif in peritoneal macrophages isolated from the ApoE-/- mice. Furthermore, a 1-week treatment with the 10% ELE diet significantly reduced migration and adhesion functions in peritoneal macrophages. These results suggest that a 10% ELE diet reduces atherosclerotic lesions and modulates macrophage function by reducing cytokine expression. PRACTICAL APPLICATION: Eucommia leaf extract (ELE) is a traditional Chinese herbal medicine that reduces atherosclerotic lesions and suppresses inflammatory cytokines expression.

Salacia chinensis stem extract and its thiosugar sulfonium constituent, neokotalanol, improves HbA1c levels in ob/ob mice.

The antidiabetic effects of a hot water extract of the stems of Salacia chinensis (SCE) were evaluated in vivo in ob/ob mice (genetically obese hyperglycemic mice). Administration of dietary feed containing 0.20 and 0.50% of SCE for 23 days to ob/ob mice significantly suppressed the elevation of both blood glucose and HbA1c levels, without significantly changing body weight and food intake. To characterize the antidiabetic effects of the thiosugar sulfonium constituent neokotalanol (1), which has potent α-glucosidase inhibitory activity, we performed a similar in vivo study. HbA1c levels were significantly suppressed in ob/ob mice after the administration of dietary feed containing 0.0003% of neokotalanol (1) for 20 days. These results indicate that SCE and neokotalanol (1) are potential leads for the development of novel antidiabetic agents.

Promotive effect of Bofutsushosan (Fangfengtongshengsan) on lipid and cholesterol excretion in feces in mice treated with a high-fat diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Bofutsushosan (fangfengtongshengsan in Chinese, BTS) is a formula in traditional Japanese Kampo medicine and Chinese medicine comprising 18 crude drugs that is used for treating obesity and metabolic syndrome. AIM OF THE STUDY: We evaluated the promotive effects of BTS on lipid and cholesterol elimination in mice. MATERIALS AND METHODS: Mice were reared with a high-fat diet containing boiled water extract of BTS for 30 days, and their biochemical parameters as well as the weight and lipid content of feces were measured. We also measured cholesterol uptake into Caco-2 cells cultured with or without BTS extract. RESULTS: The body weight and amounts of visceral fat and subcutaneous fat on day 28; the weights of epididymal, perirenal, and mesenteric fat; and the serum concentrations of triglyceride, glucose, and hemoglobin A1c on day 30 were significantly lower in the BTS extract-treated groups than in the control in a dose-dependent manner. The amounts of lipid and cholesterol in the feces collected from day 6-23 were significantly greater than in the control. When Caco-2 cells were incubated with BTS extract, the uptake of cholesterol into cells was significantly reduced in a concentration-dependent manner. Among the components of BTS, the methanol extracts of Platycodi Radix and Zingiberis Rhizoma contribute but the extracts of Ephedrae Herba and Rhei Rhizoma counteract the suppressive effect of BTS on cholesterol uptake into Caco-2 cells. CONCLUSIONS: BTS has beneficial effects on obesity and metabolic syndrome, and its mechanisms of action include the promotion of lipid elimination and the inhibition of cholesterol absorption in the intestine.

Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer's Disease.

Memory impairments in Alzheimer's disease (AD) occur due to degenerated axons and disrupted neural networks. Since only limited recovery is possible after the destruction of neural networks, preventing axonal degeneration during the early stages of disease progression is necessary to prevent AD. Polygalae Radix (roots of Polygala tenuifolia; PR) is a traditional herbal medicine used for sedation and amnesia. In this study, we aimed to clarify and analyze the preventive effects of PR against memory deficits in a transgenic AD mouse model, 5XFAD. 5XFAD mice demonstrated memory deficits at the age of 5 months. Thus, the water extract of Polygalae Radix (PR extract) was orally administered to 4-month-old 5XFAD mice that did not show signs of memory impairment. After consecutive administrations for 56 days, the PR extract prevented cognitive deficit and axon degeneration associated with the accumulation of amyloid ß (Aß) plaques in the perirhinal cortex of the 5XFAD mice. PR extract did not influence the formation of Aß plaques in the brain of the 5XFAD mice. In cultured neurons, the PR extract prevented axonal growth cone collapse and axonal atrophy induced by Aß. Additionally, it prevented Aß-induced endocytosis at the growth cone of cultured neurons. Our previous study reported that endocytosis inhibition was enough to prevent Aß-induced growth cone collapse, axonal degeneration, and memory impairments. Therefore, the PR extract possibly prevented axonal degeneration and memory impairment by inhibiting endocytosis. PR is the first preventive drug candidate for AD that inhibits endocytosis in neurons.

Preventive effect of Eucommia leaf extract on aortic media hypertrophy in Wistar-Kyoto rats fed a high-fat diet.

Eucommia ulmoides Oliver leaf extract (ELE) has been shown to have anti-hypertensive and anti-obesity effects in rats that are fed a high-fat diet (HFD). To explore the effects of chronic administration of ELE on body weight, blood pressure and aortic media thickness, 7-week-old male Wistar-Kyoto (WKY) rats were orally administered a normal diet, a 30% HFD, or a 5% ELE plus HFD ad libitum for 10 weeks. The HFD treatment caused mild obesity and hypertension in the normotensive rats, while rats receiving both ELE and the HFD had significantly lower body weights, less visceral and perirenal fat, lower blood pressure and thinner aortic media than the control rats receiving the HFD only. The plasma adiponectin/leptin ratio also improved in ELE-treated rats. Although plasma leptin levels were elevated in all HFD rats, adiponectin levels increased only in the ELE-treated rats. Anti-hypertensive and anti-obesity effects may be caused by the geniposidic acid (GEA) and/or asperuloside present in ELE. These findings suggest that chronic ELE administration prevents aortic media hypertrophy in early-stage obesity with hypertension. Long-term administration of ELE might inhibit the development of arteriosclerosis.

The Restorative Effects of Eucommia ulmoides Oliver Leaf Extract on Vascular Function in Spontaneously Hypertensive Rats.

Eucommia ulmoides Oliv. leaf is a traditional Chinese antihypertensive and antidiabetic medicine. We examined the effects of chronic Eucommia leaf extract (ELE) administration on artery function and morphology in spontaneously hypertensive rats (SHRs). ELE was orally administered via normal diet ad libitum to six-week-old male SHRs at a concentration of 5% for seven weeks. Acetylcholine (ACh)-induced endothelium-dependent relaxation, sodium nitroprusside (SNP)-induced endothelium-independent relaxation, plasma nitric oxide (NO) levels, and media thickness were assessed. ELE significantly improved ACh-induced aortic endothelium-dependent relaxation but did not affect SNP-induced endothelium-independent relaxation in the SHRs, as compared to the animals receiving normal diet. Plasma NO levels and media thickness were significantly increased and decreased, respectively, in the ELE-treated SHRs. Therefore, long-term ELE administration may effectively improve vascular function by increasing plasma NO levels and bioavailability, and by preventing vascular hypertrophy in the SHR aorta.