Yu Ping Feng San reverses cisplatin-induced multi-drug resistance in lung cancer cells via regulating drug transporters and p62/TRAF6 signalling.

Yu Ping Feng San (YPFS), an ancient Chinese herbal decoction composed of Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, has been used in the clinic for treating immune deficiency. In cancer therapy, YPFS is being combined with chemotherapy drugs to achieve improved efficacy; however, scientific evidence to illustrate this combination effect is lacking. The present study aims to demonstrate the anti-drug resistance of YPFS in cisplatin (DDP)-resistant non-small cell lung cancer cells (A549/DDP). The application of YPFS exhibited a synergistic enhancement of DDP-induced cytotoxicity as well as of the apoptotic signalling molecules. DDP-induced expression of the multi-drug-resistance efflux transporters was markedly reduced in the presence of YPFS, resulting in a higher intracellular concentration of DDP. In addition, the application of YPFS increased DDP-induced ROS accumulation and MMP depletion, decreased p62/TRAF6 signalling in DDP-treated A549/DDP cells. The co-treatment of DDP and YPFS in tumour-bearing mice reduced the tumour size robustly (by more than 80%), which was much better than the effect of DDP alone. These results indicate that YPFS can notably improve the DDP-suppressed cancer effect, which may be a consequence of the elevation of intracellular DDP via the drug transporters as well as the down regulation of p62/TRAF6 signalling.

A Chinese herbal decoction, reformulated from Kai-Xin-San, relieves the depression-like symptoms in stressed rats and induces neurogenesis in cultured neurons.

Kai-Xin-San (KXS), a Chinese herbal decoction for anti-depression, is a combination of paired-herbs, i.e. Ginseng Radix et Rhizoma (GR)-Polygalae Radix (PR) and Acori Tatarinowii Rhizoma (ATR)-Poria (PO). The make-up of the paired-herbs has been commonly revised according to syndrome differentiation and treatment variation of individual. Currently, an optimized KXS (KXS2012) was prepared by functional screening different combination of GR-PR and ATR-PO. The aim of this study was to verify the effect and underlying mechanism of KXS2012 against depression in chronic mild stress (CMS)-induced depressive rats and in primary cultures of neurons and astrocytes. In rat model, the CMS-induced depressive symptoms were markedly alleviated by the treatment with KXS2012. The CMS-suppressed neurotransmitter amounts were restored in the presence of KXS2012. And the expressions of neurotropic factors and its corresponding receptors were increased under KXS2012 administration. In cultured neurons, application of KXS2012 could promote neurogenesis by inducing the expression of synaptotagmin and dendritic spine density. Moreover, application of KXS2012 in cultured astrocytes, or in H2O2-stressed astrocytes, induced the expressions of neurotrophic factors: the increase might be associated with the modification of Erk1/2 and CREB phosphorylation. Our current results fully support the therapeutic efficacy of KXS2012 against depression in cell and animal models.

Clivorine, an otonecine pyrrolizidine alkaloid from Ligularia species, impairs neuronal differentiation via NGF-induced signaling pathway in cultured PC12 cells.

BACKGROUND: Pyrrolizidine alkaloids (PAs) are commonly found in many plants including those used in medical therapeutics. The hepatotoxicities of PAs have been demonstrated both in vivo and in vitro; however, the neurotoxicities of PAs are rarely mentioned. PURPOSE: In this study, we aimed to investigate in vitro neurotoxicities of clivorine, one of the PAs found in various Ligularia species, in cultured PC12 cells. STUDY DESIGN: PC12 cell line was employed to first elucidate the neurotoxicity and the underlying mechanism of clivorine, including cell viability and morphology change, neuronal differentiation marker and signaling pathway. METHODS: PC12 cells were challenged with series concentrations of clivorine and/or nerve growth factor (NGF). The cell lysates were collected for MTT assay, trypan blue staining, immunocytofluorescent staining, qRT-PCR and western blotting. RESULTS: Clivorine inhibited cell proliferation and neuronal differentiation evidenced by MTT assay and dose-dependently reducing neurite outgrowth, respectively. In addition, clivorine decreased the level of mRNAs encoding for neuronal differentiation markers, e.g. neurofilaments and TrkA (NGF receptor). Furthermore, clivorine reduced the NGF-induced the phosphorylations of TrkA, protein kinase B and cAMP response element-binding protein in cultured PC12 cells. CONCLUSION: Taken together, our results suggest that clivorine might possess neurotoxicities in PC12 cells via down-regulating the NGF/TrkA/Akt signaling pathway. PAs not only damage the liver, but also possess neurotoxicities, which could possibly result in brain disorders, such as depression.

Badiranji Buya Keli, a Traditional Uyghur Medicine, Induces Vasodilation in Rat Artery: Signaling Mediated by Nitric Oxide Production in Endothelial Cells.

Badiranji Buya Keli (BBK) is a traditional Uyghur medicine derived from Dracocephalum Moldavica Herba (DMH, the aerial part of Dracocephalum moldavica L.). BBK has been widely used in treating cardiovascular and cerebrovascular diseases. Here, the quality control of BBK was established by using HPLC analysis of rosmarinic acid and tilianin. After chemical standardization, the biological effects of BBK was tested. First, BBK inhibited platelet aggregation of rabbit plasma. Second, BBK induced vasodilation in rat aortic ring, and this effect was partially mediated by nitric oxide (NO) production in endothelial cells. Third, BBK induced NO production in cultured human umbilical vein endothelial cells (HUVECs). In HUVECs, the phosphorylation of endothelial NO synthase (eNOS) was markedly increased after application of BBK. Pre-treatment with the eNOS blocker N(ω) -nitro-l-arginine methyl ester hydrochloride could abolish BBK-induced NO production and eNOS phosphorylation. Taken together, these results suggest that BBK could exert beneficial effects in cardiovascular system, which may provide parts of molecular explanation to account for its traditional usage in Uyghur medicine.

The volatile oil of Nardostachyos Radix et Rhizoma induces endothelial nitric oxide synthase activity in HUVEC cells.

Nardostahyos Radix et Rhizoma (NRR; the root and rhizome of Nardostachys jatamansi DC.) is a widely used medicinal herb. Historically, NRR is being used for the treatment of cardiovascular and neurological diseases. To search for active ingredients of NRR, we investigated the vascular benefit of NRR volatile oil in (i) the vasodilation in rat aorta ring, and (ii) the release of nitric oxide (NO) and the phosphorylation of endothelial NO synthase (eNOS) in cultured human umbilical vein endothelial cells (HUVECs). By measuring the fluorescence signal in cultures, application of NRR volatile oil resulted in a rapid activation of NO release as well as the phosphorylation of eNOS: both inductions were markedly reduced by L-NAME. In parallel, the phosphorylation level of Akt kinase was markedly increased by the oil treatment, which was partially attenuated by PI3K/Akt inhibitor LY294002. This inhibitor also blocked the NRR-induced NO production and eNOS phosphorylation. In HUVECs, application of NRR volatile oil elevated the intracellular Ca(2+) level, and BAPTA-AM, a Ca(2+) chelator, reduced the Ca(2+) surge: the blockage were also applied to NRR-induced eNOS phosphorylation and NO production. These findings suggested the volatile oil of NRR was the major ingredient in triggering the vascular dilatation, and which was mediated via the NO production.

The extract of Ziziphus jujuba fruit (jujube) induces expression of erythropoietin via hypoxia-inducible factor-1α in cultured Hep3B cells.

The fruit of Ziziphus jujuba Mill., known as jujube or Chinese date, is commonly consumed as health supplement or herbal medicine worldwide. To study the beneficial role of jujube in enhancing hematopoietic function, we investigated its roles on the expression of erythropoietin in cultured Hep3B human hepatocellular carcinoma cells. Application of chemically standardized jujube water extract stimulated erythropoietin expression in a dose-dependent manner, with the highest response by ~ 100 % of increase. A plasmid containing hypoxia response element, a critical regulator for erythropoietin transcription, was transfected into Hep3B cells. Application of jujube water extract onto the transfected cells induced the transcriptional activity of the hypoxia response element. To account for its transcriptional activation, the expression of hypoxia-inducible factor-1α was increased after treatment with jujube water extract: the increase was in both mRNA and protein levels. These results confirmed the hematopoietic function of jujube in the regulation of erythropoietin expression in liver cells.

Ferulic acid enhances the chemical and biological properties of astragali radix: a stimulator for danggui buxue tang, an ancient Chinese herbal decoction.

Danggui buxue tang, an ancient formula composed of astragali radix and Angelicae sinensis radix, has been used for treating menopausal irregularity in women for more than 800 years in China. In danggui buxue tang, the complete functions of astragali radix require the assistance of Angelicae sinensis radix, and both herbs have to work harmoniously in order to achieve the maximal therapeutic purposes. In order to analyze the relationship of the two herbs, the role of ferulic acid, a major chemical within Angelicae sinensis radix, in chemical and biological properties of astragali radix was determined. Using ferulic acid in the extraction of astragali radix, the amounts of astragaloside IV, calycosin, and formononetin were increased in the final extract; however, the astragali radix polysaccharide showed a minor increase. The chemical-enriched astragali radix extract showed robust induction in osteogenic and estrogenic activities in cultured osteosarcoma MG-63 and breast MCF-7 cells. However, ferulic acid itself did not show such biological responses. The current results strongly suggest that Angelicae sinensis radix-derived ferulic acid is a positive regulator for danggui buxue tang, which enhanced the solubilities of active ingredients derived from astragali radix, and which therefore increased the biological efficacies of danggui buxue tang.

Flavonoids, derived from traditional Chinese medicines, show roles in the differentiation of neurons: possible targets in developing health food products.

Flavonoids, a family of phenolic compounds, are distributed in a variety of fruits, vegetables, tea, and wine. More importantly, many flavonoids are served as the active ingredients in traditional Chinese herbal medicines, which in general do not have side effects. Several lines of evidence support that flavonoids have impacts on many aspects of human health, including anti-tumor, anti-oxidation, and anti-inflammation. Recently, there is significant attention focused on the neuronal beneficial effects of flavonoids, including the promotion of nervous system development, neuroprotection against neurotoxin stress, as well as the promotion of memory, learning, and cognitive functions. Here, the activities of flavonoids on the development of nervous system are being summarized and discussed. The flavonoids from diverse herbal medicines have significant effects in different developmental stages of nervous systems, including neuronal stem cell differentiation, neurite outgrowth, and neuronal plasticity. These findings imply that flavonoids are potential candidates for the development of health supplements in preventing birth defects and neuronal diseases.

Flavonoids induce the expression of synaptic proteins, synaptotagmin, and postsynaptic density protein-95 in cultured rat cortical neuron.

Flavonoids, a family of phenolic compounds, are widely present in our daily diet and exist in traditional Chinese medicines, in which they act as the major active functional ingredients. Different lines of evidence indicate that flavonoids have positive impacts on human health. Here, different subclasses of flavonoids were analyzed for their inductive roles in promoting the expression of synaptic proteins, synaptotagmin, and post-synaptic density protein-95 in cultured rat cortical neurons. Among the screened 65 flavonoids, (-)-catechin, luteolin, and isorhamnetin, in micromolar concentration, were found to induce the expression of synaptic proteins in a dose-dependent manner: the induction values were from 2- to 8-fold that of the control. Similar results were revealed in the flavonoid-treated hippocampal neurons. The identification of these synapse-promoting flavonoids could be very useful in finding potential drugs, or food supplements, for treating various neurodegenerative diseases, including Alzheimer's disease and depression.

Flavonoids induce the synthesis and secretion of neurotrophic factors in cultured rat astrocytes: a signaling response mediated by estrogen receptor.

Neurotrophic factors are playing vital roles in survival, growth, and function of neurons. Regulation of neurotrophic factors in the brain has been considered as one of the targets in developing drug or therapy against neuronal disorders. Flavonoids, a family of multifunctional natural compounds, are well known for their neuronal beneficial effects. Here, the effects of flavonoids on regulating neurotrophic factors were analyzed in cultured rat astrocytes. Astrocyte is a major secreting source of neurotrophic factors in the brain. Thirty-three flavonoids were screened in the cultures, and calycosin, isorhamnetin, luteolin, and genistein were identified to be highly active in inducing the synthesis and secretion of neurotrophic factors, including nerve growth factor (NGF), glial-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF). The inductions were in time- and dose-dependent manners. In cultured astrocytes, the phosphorylation of estrogen receptor was triggered by application of flavonoids. The phosphorylation was blocked by an inhibitor of estrogen receptor, which in parallel reduced the flavonoid-induced expression of neurotrophic factors. The results proposed the role of flavonoids in protecting brain diseases, and therefore these flavonoids could be developed for health food supplement for patients suffering from neurodegenerative diseases.

Chemical and biological assessment of angelica roots from different cultivated regions in a chinese herbal decoction danggui buxue tang.

Roots of Angelica sinensis (Danggui) have been used in promoting blood circulation as herbal medicine for over 2000 years in China. Another species of Angelica roots called A. gigas is being used in Korea. To reveal the efficiency of different Angelica roots, the chemical and biological properties of Angelica roots from different cultivated regions were compared. Roots of A. sinensis contained higher levels of ferulic acid, Z-ligustilide, and senkyunolide A, while high amounts of butylphthalide and Z-butylenephthalide were found in A. gigas roots. The extracts deriving from A. gigas roots showed better effects in osteogenic and estrogenic properties than that of A. sinensis from China. However, this difference was markedly reduced when the Angelica roots were being prepared in a Chinese herbal decoction together with Astragali Radix as Danggui Buxue Tang. In contrast, the herbal decoction prepared from A. sinensis roots showed better responses in cell cultures. In addition, the extracts of A. gigas roots showed strong cell toxicity both as single herb and as Danggui Buxue Tang. This result revealed the distinct properties of Angelica roots from China and Korea suggesting the specific usage of herb in preparing a unique herbal decoction.

Importance of wine-treated Angelica Sinensis Radix in Si Wu Tang, a traditional herbal formula for treating women's ailments.

Si Wu Tang (Four Agents Decoction), a traditional Chinese decoction composed of Angelica Sinensis Radix, Chuanxiong Rhizoma, Paeoniae Radix Alba, and Rehmanniae Radix Praeparata in a ratio of 1 : 1 : 1 : 1, has been used to treat women's diseases for more than a thousand years. According to the original description of Si Wu Tang, Angelica Sinensis Radix should be treated with wine. However, the importance of this wine-treated Angelica Sinensis Radix in Si Wu Tang's function has not been identified. In this article, the chemical and biological properties of two decoctions processed in different ways (Si Wu Tang with crude Angelica Sinensis Radix and Si Wu Tang with wine-treated Angelica Sinensis Radix) were compared for examination. The herbal decoction Si Wu Tang prepared from wine-treated Angelica Sinensis Radix contained much different amounts of its active compounds. Compared with Si Wu Tang using crude Angelica Sinensis Radix, Si Wu Tang prepared from wine-treated Angelica Sinensis Radix had better biological responses. Therefore, these findings accentuate the functional importance of herbs treated with wine in the Chinese decoction.

Fo shou san, an ancient herbal decoction prepared from angelicae sinensis radix and chuanxiong rhizoma, induces erythropoietin expression: a signaling mediated by the reduced degradation of hypoxia-inducible factor in cultured liver cells.

Fo Shou San (FSS) is an ancient herbal decoction composed of Angelicae Sinensis Radix (ASR; Danggui) and Chuanxiong Rhizoma (CR; Chuanxiong) in a ratio of 3:2. FSS is mainly prescribed for patients having a deficiency of blood supply, and it indeed has been shown to stimulate the production of erythropoietin (EPO) in cultured cells. In order to reveal the mechanism of this FSS-induced EPO gene expression, the upstream regulatory cascade, via hypoxia-induced signaling, was revealed here in cultured hepatocellular carcinoma cell line Hep3B. The induction of EPO gene expression, triggered by FSS, was revealed in cultured hepatocytes by: (i) the increase of EPO mRNA; and (ii) the activation of the hypoxia response element (HRE), an upstream regulator of the EPO gene. The FSS-induced EPO gene expression was triggered by an increased expression of hypoxia-inducible factor-1 α (HIF-1 α) protein; however, the mRNA expression of HIF-1 α was not altered by the treatment of FSS. The increased HIF-1 α was a result of reduced protein degradation after the FSS treatment. The current results therefore provide one of the molecular mechanisms of this ancient herbal decoction for its hematopoietic function.

Trillin, a steroidal saponin isolated from the rhizomes of Dioscorea nipponica, exerts protective effects against hyperlipidemia and oxidative stress.

ETHNOPHARMACOLOGICAL EVIDENCE: Numerous efforts have been conducted in searching for effective agents against cardiovascular diseases, in particular from herbal medicines. The rhizome of Dioscorea nipponica (Dioscoreae Nipponicae Rhizoma) is a traditional Chinese herb being prescribed to improve the blood circulation. Here, we identified a steroidal saponin trillin from Dioscorea nipponica, which showed robust anti-hyperlipidemic effects. MATERIALS AND METHODS: Rats were induced for hyperlipidemia and subjected to the drug treatment. The anti-hyperlipidemic effects of trillin were evaluated by different biochemical assays. RESULTS: In hyperlipidemic rat model, fed with high-fat diet, the blood levels of cholesterol, triglyceride, low density lipoprotein (LDL) and high density lipoprotein (HDL) were increased. The intra-peritoneal administration of trillin into those rats significantly improved the bleeding and blood coagulation time, and in parallel the treatment restored the levels of cholesterol, glyceride, LDL and HDL back to the normal condition. In addition, the administration of trillin in rats exerted beneficial effects in improving the levels of lipid peroxidation and superoxide dismutase activity. CONCLUSION: This was the first time to reveal the anti-hyperlipidemic and anti-oxidative effects of trillin. These results would be important in developing food supplements for health improvements and therapeutic drugs against hyperlipidemia and cardiovascular diseases in future.

Fo Shou San, an ancient Chinese herbal decoction, protects endothelial function through increasing endothelial nitric oxide synthase activity.

Fo Shou San (FSS) is an ancient herbal decoction comprised of Chuanxiong Rhizoma (CR; Chuanxiong) and Angelicae Sinensis Radix (ASR; Danggui) in a ratio of 2:3. Previous studies indicate that FSS promotes blood circulation and dissipates blood stasis, thus which is being used widely to treat vascular diseases. Here, we aim to determine the cellular mechanism for the vascular benefit of FSS. The treatment of FSS reversed homocysteine-induced impairment of acetylcholine (ACh)-evoked endothelium-dependent relaxation in aortic rings, isolated from rats. Like radical oxygen species (ROS) scavenger tempol, FSS attenuated homocysteine-stimulated ROS generation in cultured human umbilical vein endothelial cells (HUVECs), and it also stimulated the production of nitric oxide (NO) as measured by fluorescence dye and biochemical assay. In addition, the phosphorylation levels of both Akt kinase and endothelial NO synthases (eNOS) were markedly increased by FSS treatment, which was abolished by an Akt inhibitor triciribine. Likewise, triciribine reversed FSS-induced NO production in HUVECs. Finally, FSS elevated intracellular Ca(2+) levels in HUVECs, and the Ca(2+) chelator BAPTA-AM inhibited the FSS-stimulated eNOS phosphorylation. The present results show that this ancient herbal decoction benefits endothelial function through increased activity of Akt kinase and eNOS; this effect is causally via a rise of intracellular Ca(2+) and a reduction of ROS.

Chemical and biological assessment of Angelicae Sinensis Radix after processing with wine: an orthogonal array design to reveal the optimized conditions.

The roots of Angelica sinensis [Angelica Sinensis Radix (ASR)] have been used as a common health food supplement for women's care for thousands of years in China. According to Asian tradition, ASR could be processed with the treatment of wine, which subsequently promoted the biological functions of ASR. By chemical and biological assessments, an orthogonal array design was employed here to determine the roles of three variable parameters in the processing of ASR, including oven temperature, baking time, and flipping frequency. The results suggested that oven temperature and baking time were two significant factors, while flipping frequency was a subordinate factor. The optimized condition of processing with wine therefore was considered to be heating in an oven at 80 °C for 90 min with flipping twice per hour. Under the optimized processing conditions, the solubilities of ferulic acid and Z-ligustilide from ASR were markedly increased and decreased, respectively. In parallel, the biological functions of processed ASR were enhanced in both anti-platelet aggregation and estrogenic activation; these increased functions could be a result of the altered levels of ferulic acid and Z-ligustilide in wine-processed ASR. Thus, the chemical and biological assessment of the processed ASR was in full accordance with the Chinese old tradition.

Flavonoids from Radix Astragali induce the expression of erythropoietin in cultured cells: a signaling mediated via the accumulation of hypoxia-inducible factor-1α.

Radix Astragali (RA) is commonly used as a health food supplement to reinforce the body vital energy. Flavonoids, including formononetin, ononin, calycosin, and calycosin-7-O-ß-d-glucoside, are considered to be the major active ingredients within RA. Here, we provided different lines of evidence that the RA flavonoids stimulated the expression of erythropoietin (EPO), the central regulator of red blood cell mass, in cultured human embryonic kidney fibroblasts (HEK293T). A plasmid containing hypoxia response element (HRE), a critical regulator for EPO transcription, was tagged upstream of a firefly luciferase gene, namely, pHRE-Luc, which was being transfected into fibroblasts. The application of RA flavonoids onto the transfected cells induced the transcriptional activity of HRE. To account for the transcriptional activation after the treatment of flavonoids, the expression of hypoxia-inducible factor-1α (HIF-1α) was markedly increased: The increase was in both mRNA and protein levels. In addition, the degradation of HIF-1α was reduced under the effect of flavonoids. The regulation of HIF-1α therefore could account for the activation of EPO expression mediated by the RA flavonoids. The current results therefore reveal the function of this herb in enhancing hematopoietic functions.

The expression of erythropoietin triggered by danggui buxue tang, a Chinese herbal decoction prepared from radix Astragali and radix Angelicae Sinensis, is mediated by the hypoxia-inducible factor in cultured HEK293T cells.

ETHNOPHARMACOLOGICAL EVIDENCE: Danggui buxue tang (DBT), a Chinese medicinal decoction that is being commonly used as hematopoietic medicine to treating woman menopausal irregularity, contains two herbs: radix Astragali and radix Angelicae Sinensis. Pharmacological results indicate that DBT can stimulate the production of erythropoietin (EPO), a specific hematopoietic growth factor, in cultured cells. AIM OF THE STUDY: In order to reveal the mechanism of DBT's hematopoietic function, this study investigated the activity of the DBT-induced EPO expression and the upstream regulatory cascade of EPO via hypoxia-induced signaling in cultured kidney fibroblasts (HEK293T). MATERIALS AND METHODS: DBT-induced mRNA expressions were revealed by real-time PCR, while the change of protein expressions were analyzed by Western blotting. For the analysis of hypoxia-dependent signaling, a luciferase reporter was used to report the transcriptional activity of hypoxia response element (HRE). RESULTS: The plasmid containing HRE, being transfected into HEK293T, was highly responsive to the challenge of DBT application. To account for the transcriptional activation of HRE, DBT treatment was shown to increase the mRNA and protein expressions of hypoxia-inducible factor-1α (HIF-1α). In addition, the activation of Raf/MEK/ERK signaling pathway by DBT could also enhance the translation of HIF-1α, suggesting the dual actions of DBT in stimulating the EPO expression in kidney cells. CONCLUSION: Our study indicates that HIF pathway plays an essential role in directing DBT-induced EPO expression in kidney. These results provide one of the molecular mechanisms of this ancient herbal decoction for its hematopoietic function.

Galangin, a flavonol derived from Rhizoma Alpiniae Officinarum, inhibits acetylcholinesterase activity in vitro.

Acetylcholinesterase (AChE) inhibitors are widely used for the treatment of Alzheimer's disease (AD). Several AChE inhibitors, e.g. rivastigmine, galantamine and huperzine are originating from plants, suggesting that herbs could potentially serve as sources for novel AChE inhibitors. Here, we searched potential AChE inhibitors from flavonoids, a group of naturally occurring compounds in plants or traditional Chinese medicines (TCM). Twenty-one flavonoids, covered different subclasses, were tested for their potential function in inhibiting AChE activity from the brain in vitro. Among all the tested flavonoids, galangin, a flavonol isolated from Rhizoma Alpiniae Officinarum, the rhizomes of Alpiniae officinarum (Hance.) showed an inhibitory effect on AChE activity with the highest inhibition by over 55% and an IC(50) of 120 microM and an enzyme-flavonoid inhibition constant (K(i)) of 74 microM. The results suggest that flavonoids could be potential candidates for further development of new drugs against AD.

Antihyperlipidemic effect of protodioscin, an active ingredient isolated from the rhizomes of Dioscorea nipponica.

Developing drugs against metabolic-related disorders, including obesity and hyperlipidemia, is of importance for human health. Here, a bioactive phytochemical, protodioscin, isolated from the rhizomes of Dioscorea nipponica (Rhizoma Dioscoreae Nipponicae), was identified for its anti-hyperlipidemic effect. In hyperlipidemic rats, the post-administration of protodioscin significantly reduced the time of blood coagulation. In addition, the blood levels of triglyceride, cholesterol, low-density and high-density lipoproteins were also changed accordingly. Taken together, this was the first report of an antihyperlipidemic effect of protodioscin. Its great availability in various vegetables and medicinal plants will be useful in developing health food supplement(s) and/or drug(s) against hyperlipidemia.