Low Dose of Emodin Inhibits Hypercholesterolemia in a Rat Model of High Cholesterol.

BACKGROUND Emodin has been widely used in traditional Chinese medicine, but few studies have tried to understand the mechanism of its anti-hypercholesterolemic effect. MATERIAL AND METHODS To delineate the underlying pathways, high-cholesterol diet (HCD)-fed Sprague-Dawley rats were orally administrated emodin or the lipid-lowering medicine simvastatin. Emodin was administered at 10, 30, or 100 mg/kg, while simvastatin was administered at 10 mg/kg. Parameters measured included lipid profiles (serum total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, aorta endothelium-dependent vasorelaxation in response to acetylcholine, and nitric oxide (NO) production. RT-qPCR and western blotting were performed to evaluate aortic endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), and hepatic LDL receptor (LDLR). Indices of liver and serum oxidation were also measured. RESULTS The atherogenic index was increased by the HCD but significantly reduced in all treatment groups. The HCD-fed experimental group treated with emodin at 10 mg/kg had significantly lower serum total-C and LDL-C and improved aorta vasorelaxation and enhanced NO production. Also, emodin significantly attenuated the lipid profiles and restored endothelial function, as reflected by upregulated expression of hepatic LDLR and p-eNOS, respectively. Furthermore, emodin at 10 mg/kg significantly enhanced superoxide dismutase activity, lowered the malondialdehyde level in both liver and serum, and enhanced catalase activity in serum. CONCLUSIONS The ability of emodin to inhibit hypercholesterolemia in HCD-fed rats was associated with lower serum total-C and LDL-C, restoration of aortic endothelial function, and improved antioxidant capacity. Low-dose emodin showed better protection of aortic endothelium and better antioxidant activity than did higher doses.

Using pollen grains as novel hydrophilic solid-phase extraction sorbents for the simultaneous determination of 16 plant growth regulators.

In this article, pollen grains were for the first time used as a hydrophilic solid-phase extraction (HILIC-SPE) sorbent for the determination of 16 plant growth regulators (PGRs) in fruits and vegetables. Fourier transform infrared spectroscopy (FT-IR), scanning electronic microscopy (SEM) and nitrogen sorption porosimetry (NSP) were used to investigate the chemical structure and the surface properties of the pollen grains. Pollen grains exhibited an excellent adsorption capacity for some polar compounds due to their particular functional groups. Several parameters influencing extraction performance were investigated. A green and simple HILIC-SPE-method using pollen grain cartridge for purification of fruit and vegetable extractions, followed by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry (UHPLC-MS/MS) was established. Good linear relationships were obtained for 16 PGRs with correlation coefficients (R) above 0.9980. The limits of detection (LODs) of 16 PGRs in cucumber were in the range of 0.01-1.10 µg · kg(-1). Reproducibility of the method was evaluated by intra-day and inter-day precisions with relative standard deviations (RSDs), which were less than 14.4%. We successfully applied this methodology to analyze 16 PGRs in 8 different kinds of fruits and vegetables. The recoveries from samples spiked with 16 PGRs were from 80.5% to 119.2%, with relative standard deviations less than 15.0%.

Ethanolic extract of rhizome of Ligusticum chuanxiong Hort. (chuanxiong) enhances endothelium-dependent vascular reactivity in ovariectomized rats fed with high-fat diet.

The rhizome of Ligusticum chuanxiong Hort. (LC), also known as chuanxiong, is a very common herb widely used to treat cardiovascular and cerebrovascular diseases. It is also used as a major ingredient in soups for regular consumption to promote good health. To study the protective effect of LC ethanolic extract (LCEE, 600 mg per kg per day, p.o.) on the integrity of the vascular system, ovariectomized (OVX) rats were fed with a high-fat diet (HFD) plus LCEE for 12 weeks. The animal model was used to mimic the dyslipidemic condition seen in postmenopausal women. LCEE was found significantly to reduce the body weight gain, improve serum lipid profiles (by lowering total cholesterol and low density lipoprotein cholesterol but raising high density lipoprotein cholesterol) and protect vascular endothelium in the HFD-fed OVX rats. It is postulated that LCEE could exert its vascular protective effect through multiple targets by (1) improving serum lipid profiles to reduce the detrimental effects of cholesterol; (2) reducing the ROS level in the body via enhancing the hepatic anti-oxidative activity or antioxidant level to scavenge the reactive oxygen species generated in the postmenopausal hypercholesterolemic condition; (3) stimulating eNOS-derived nitric oxide production; (4) counteracting the up-regulation of inflammatory cytokine (TNF-α, VCAM-1 and ICAM-1) expressions so as to reduce endothelium damage.

Ligusticum chuanxiong prevents ovariectomy-induced liver and vascular damage in rats.

Post-menopause, there is an increase in body weight, visceral adiposity, and risk of developing non-alcoholic fatty liver disease (NAFLD), which leads to various cardiovascular diseases (CVDs). Some natural products have proven useful for counteracting the detrimental effects of menopause. The rhizome of Ligusticum chuanxiong Hort. (LC) is a well-known medicinal herb widely used in Chinese communities for the treatment of CVDs. The hepatic and vascular protective effects of LC ethanolic extract under postmenopausal conditions were investigated on ovariectomized (OVX) rats supplemented with or without LC ethanolic extract (600 mg/kg body weight/day, p.o.) or 17ß-estradiol (1 mg/kg body weight/day, p.o.) for 12 weeks. The current findings demonstrated that consumption of LC ethanolic extract could reduce the body weight gain, improve serum lipid profile (lowering low density lipoprotein cholesterol but raising high density lipoprotein cholesterol), combat NAFLD, and protect vascular endothelium in the OVX rats. The beneficial effects of LC may be associated with its antioxidant or vasorelaxant compounds, which enhance the levels of hepatic antioxidant enzymes and up-regulate endothelial nitric oxide synthase mRNA expression, respectively. Taken together, LC may be a promising natural supplement for postmenopausal women to prevent NAFLD and CVDs.

Aqueous extract of danshen (Salvia miltiorrhiza Bunge) protects ovariectomized rats fed with high-fat diet from endothelial dysfunction.

OBJECTIVE: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in postmenopausal women. Danshen, the dried root of Salvia miltiorrhiza Bunge, has been used clinically in China to treat CVD and dyslipidemia in postmenopausal women, and its major active ingredients have been found to have an estrogenic effect. The aim of this study was to elucidate the underlying mechanism of danshen's protective effects on vascular function in an ovariectomized (OVX) hyperlipidemic rat model. METHODS: Thirty-five 6-month-old female Sprague-Dawley rats were randomly divided into five groups: sham-operated rats with low-fat control diet + vehicle, sham-operated rats with high-fat diet (HFD) + vehicle, OVX rats with HFD + vehicle, OVX rats with HFD + 17ß-estradiol (1 mg kg d, PO), and OVX rats with HFD + danshen aqueous extract (600 mg kg d, PO). After 12 weeks of treatment, gains in body weight and serum lipid profile levels in rats were measured and histological examination of livers was carried out. Vascular function was evaluated by measuring relaxation responses. Molecular mechanisms were also analyzed in isolated aorta. RESULTS: Treatment with danshen aqueous extract reduced body weight gain, improved serum lipid profiles, and prevented formation of fatty liver induced by HFD and OVX. In addition, danshen could increase endothelial-dependent vasorelaxation and displayed vasoprotection in OVX rats fed with HFD, primarily by stimulating nitric oxide (NO) production, up-regulating the mRNA expression of endothelial NO synthase, and down-regulating the mRNA expression of tumor necrosis factor α, intercellular cell adhesion molecule-1, and vascular cell adhesion molecule-1 in the isolated aortas. CONCLUSIONS: We conclude for the first time that danshen aqueous extract could protect OVX rats fed with HFD from endothelial dysfunction. Its effect may be related to its abilities to normalize serum lipid profiles and enhance NO availability in the vascular system. Our findings indicate that danshen aqueous extract could be a promising natural supplement for postmenopausal women for preventing CVD.

Suppression of diet-induced hypercholesterolemia by turtle jelly, a traditional chinese functional food, in rats.

Consumption of functional foods for lowering serum cholesterol has globally gained acceptance by the general public. Turtle jelly (TJ), also called gui-ling-gao, is a popular traditional functional food in southern China. The hypocholesterolemic effect of consuming TJ was investigated in rats fed with normal diet, high-cholesterol diet or high-cholesterol diet supplemented with simvastatin (3 mg/kg bw per day, p.o.) or TJ (3.3 or 10 mL/kg bw per day, p.o.) for 30 days. TJ markedly reversed the increased serum total cholesterol, increased high-density lipoprotein, and decreased high-density lipoprotein induced by hypercholesterolemic diet with a dose-dependent improvement on the atherogenic index. It also demonstrated good hepatoprotective function by reducing fat depositions and overall lipid contents in the liver and increasing the activities of hepatic antioxidative enzymes. The blunted nitric oxide/endothelium-mediated aortic relaxation in rats fed with hypercholesterolemic diet was partially restored after TJ consumption. It is postulated that the hypocholesterolemic effect is the primary beneficial effect given by TJ; it then leads to secondary beneficial effects such as vasoprotective and hepatoprotective functions. The results revealed that TJ could block the downregulation of LDLR and PEPCK and upregulation of PPARα mRNA and protein expressions in the livers of rats fed with hypercholesterolemic diet.

A review of the anticancer and immunomodulatory effects of Lycium barbarum fruit.

The anticancer effects of traditional Chinese medicine (TCM) have attracted the attention of the public vis-à-vis existing cancer therapies with various side effects. Lycium barbarum fruit, commonly known as Gou Qi Zi in China, is a potential anticancer agent/adjuvant. Its major active ingredients, L. barbarum polysaccharides (LBP), scopoletin and 2-O-ß-D-glucopyranosyl-L-ascorbic acid (AA-2ßG), are found to have apoptotic and antiproliferative effects on cancer cell lines. Moreover, LBP also contributes to body's immunomodulatory effects and enhances effects of other cancer therapies. It is not known whether there are any undesirable effects. Further studies on its pharmacological mechanisms and toxicology could facilitate a safe usage of this TCM herb.

A review of the pharmacological effects of Arctium lappa (burdock).

Arctium lappa, commonly known as burdock, is being promoted/recommended as a healthy and nutritive food in Chinese societies. Burdock has been used therapeutically in Europe, North America and Asia for hundreds of years. The roots, seeds and leaves of burdock have been investigated in view of its popular uses in traditional Chinese medicine (TCM). In this review, the reported therapeutic effects of the active compounds present in the different botanical parts of burdock are summarized. In the root, the active ingredients have been found to "detoxify" blood in terms of TCM and promote blood circulation to the skin surface, improving the skin quality/texture and curing skin diseases like eczema. Antioxidants and antidiabetic compounds have also been found in the root. In the seeds, some active compounds possess anti-inflammatory effects and potent inhibitory effects on the growth of tumors such as pancreatic carcinoma. In the leaf extract, the active compounds isolated can inhibit the growth of micro-organisms in the oral cavity. The medicinal uses of burdock in treating chronic diseases such as cancers, diabetes and AIDS have been reported. However, it is also essential to be aware of the side effects of burdock including contact dermatitis and other allergic/inflammatory responses that might be evoked by burdock.

Evaluation of anti-oxidant capacity of root of Scutellaria baicalensis Georgi, in comparison with roots of Polygonum multiflorum Thunb and Panax ginseng CA Meyer.

In Chinese communities, regular consumption of Chinese-medicated diets (CMD) (usually in the form of soup) is a traditional practice to promote health and prevent disease development. The overall improvement of health conditions is believed to be correlated with the anti-oxidant potentials of these herbs. Huangqin, roots of Scutellaria baicalensis Georgi (Lamiaceae), is one of the herbs commonly used in CMD. In this study, the anti-oxidant capacities of Huangqin extracts (water, ethanol and ether extracts) were evaluated and compared to commonly used CMD herbs, Heshouwu, roots of Polygonum multiflorum Thunb (Polygonaceae) and Renshen (or Ginseng), roots of Panax ginseng CA Meyer (Araliaceae). The anti-oxidant capacities were measured by using both cell-free assay [ferric reducing/anti-oxidant power (FRAP)] and biological methods [2,2'-azobis-(2-amidinopropane) (AAPH)-induced haemolysis assay and H(2)O(2)-induced cell damage on H9C2 cells]. Additionally, the total phenolic content was measured using Folin-Ciocalteu methods. Water extract of Huangqin has the highest anti-oxidant activities compared to the ethanol and ether extracts. A positive relationship between the anti-oxidant effects and total phenolic contents of extracts was demonstrated. This shows that Huangqin could be an effective dietary anti-oxidant that can be consumed regularly as a functional food for the prevention of oxidant/free radical-related diseases.

Formononetin, an isoflavone, relaxes rat isolated aorta through endothelium-dependent and endothelium-independent pathways.

We evaluated the vasorelaxation effects of formononetin, an isoflavone/phytoestrogen found abundantly in Astragalus mongholicus Bunge, on rat isolated aorta and the underlying mechanisms involved. Cumulative administration of formononetin, genistein, daidzein and biochanin A relaxed phenylephrine-preconstricted aorta. Formononetin and biochanin A caused a similar magnitude of relaxation whereas daidzein was least potent. Mechanical removal of endothelium, L-NAME (100 microM) and methylene blue (10 microM) suppressed formononetin-induced relaxation. Formononetin increased endothelial nitric oxide (NO) synthase (eNOS), but not inducible NO synthase, activity with an up-regulation of eNOS mRNA and p-eNOS(Ser1177) protein expression. In endothelium-denuded preparations, formononetin-induced vasorelaxation was significantly reduced by glibenclamide (3 microM) and iberiotoxin (100 nM), and a combination of glibenclamide (3 microM) plus iberiotoxin (100 nM) abolished the relaxation. In contrast, formononetin-elicited endothelium-independent relaxation was not altered by ICI 182,780 (10 microM, an estrogen receptor (ER alpha/ER beta) antagonist) or mifepristone (10 microM, a progesterone receptor antagonist). In single aortic smooth muscle cells, formononetin caused opening of iberiotoxin-sensitive Ca(2+)-activated K(+) (BK(Ca)) channels and glibenclamide-sensitive adenosine triphosphate (ATP)-dependent K(+) (K(ATP)) channels. Thus, our results suggest that formononetin caused vascular relaxation via endothelium/NO-dependent mechanism and endothelium-independent mechanism which involves the activation of BK(Ca) and K(ATP) channels.

Suppression of diet-induced hypercholesterolemia by scutellarin in rats.

Hypercholesterolemia is a major risk factor for the development and progression of cardiovascular diseases including atherosclerosis. A major active ingredient, scutellarin, from the plant Erigeron breviscapus was investigated for its hypocholesterolemic and atheroscleroprotective effects (30 and 100 mg/kg/day, P. O.). The serum lipid profile (total cholesterol, triglycerides, high density lipoprotein cholesterol and low density lipoprotein cholesterol) was monitored and aortic functions in Sprague-Dawley rats fed with normal diet, atherogenic diet or atherogenic diet plus oral administration of either scutellarin or simvastatin (a positive control) were tested. It was found that scutellarin markedly attenuated the increased serum total cholesterol induced by atherogenic diet. It caused a significant reduction in the atherogenic index. In addition, scutellarin administration could significantly enhance acetylcholine-induced nitrate/nitrite production, increase the gene expression of endothelial nitric oxide synthase and improve acetylcholine-induced endothelium-dependent vasorelaxation in rat isolated aortas. These data revealed that scutellarin could reduce the atherogenic properties of dietary cholesterol in rats. However, whether scutellarin's atheroscleroprotective potential targets endothelial function directly or indirectly on its antioxidative activity remains to be determined.