The cytokine "macrophage migration inhibitory factor (MIF)" is generally recognized as a proinflammatory cytokine, and MIF is involved in broad range of acute and chronic inflammatory states. With regard to glucose metabolism and insulin secretion, MIF is produced by pancreatic ß cells and acts as a positive regulator of insulin secretion. In contrast, it is evident that MIF expressed in adipose tissues causes insulin resistance. Concerning MIF gene analysis, we found four alleles: 5-, 6-, 7- and 8-CATT at position -794 of MIF gene in a Japanese population. Genotypes without the 5-CATT allele were more common in the obese subjects than in the lean or overweight groups. It is conceivable that promoter polymorphism in the MIF gene is profoundly linked with obesity relevant to lifestyle diseases, such as diabetes. Obesity has become a serious social issue due to the inappropriate nutritional balance, and the consumption of functional foods (including functional foods to reduce fat mass) is expected to overcome this issue. In this context, MIF would be a reliable quantitative biomarker to evaluate the effects of functional foods on adiposity.

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Accumulating epidemiological and clinical evidence shows that inflammation is an important risk factor for various human diseases. Thus, suppressing chronic inflammation has the potential to delay, prevent, and control various chronic diseases, including cerebrovascular, cardiovascular, joint, skin, pulmonary, blood, lymph, liver, pancreatic, and intestinal diseases. Various natural products from traditional Chinese medicine (TCM) have been shown to safely suppress proinflammatory pathways and control inflammation-associated disease. In vivo and/or in vitro studies have demonstrated that anti-inflammatory effects of TCM occur by inhibition of the expression of master transcription factors (for example, nuclear factor-?B (NF-?B)), pro-inflammatory cytokines (for example, tumor necrosis factor-a (TNF-a), chemokines (for example, chemokine (C-C motif) ligand (CCL)-24), intercellular adhesion molecule expression and pro-inflammatory mediators (for example, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2)). However, a handful of review articles have focused on the anti-inflammatory activities of TCM and explore their possible mechanisms of action. In this review, we summarize recent research attempting to identify the anti-inflammatory constituents of TCM and their molecular targets that may create new opportunities for innovation in modern pharmacology.

Transcriptomics, proteomics, and metabolomics are three major platforms of comprehensive omics analysis in the science of food and complementary medicine. Other omics disciplines, including those of epigenetics and microRNA, are matters of increasing concern. The increased use of the omics approach in food science owes much to the recent advancement of technology and bioinformatic methodologies. Moreover, many researchers now put the combination of multiple omics analysis (integrated omics) into practice to exhaustively understand the functionality of food components. However, data analysis of integrated omics requires huge amount of work and high skill of data handling. A database of nutritional omics data was constructed by the authors, which should help food scientists to analyze their own omics data more effectively. In addition, a novel tool for the easy visualization of omics data was developed by the authors' group. The tool enables one to overview the changes of multiple omics in the KEGG pathway. Research in traditional and complementary medicine will be further facilitated by promoting the integrated omics research of food functionality. Such integrated research will only be possible with the effective collaboration of scientists with different backgrounds.

Young individuals typically have a dry-heat (?? zào rè) constitution and feel overly stimulated. This study observes specialties on the right-bar (?? yòu guan) section of the radial-arterial pulse of healthy young subjects, and investigates pulse variations induced by different attribute foods. Chinese medical doctors grouped thirty subjects into heat and non-heat constitutions. Each subject took water, aged ginger tea, and coconut water, well recognized as neutral, hot, and cold drinks, on different visits. The current study observed physiological signals induced by the samples using novel noninvasive sphygmography and a blood pressure monitor. As the baseline bigger percussion wave, dicrotic wave, and area in the sphygmogram of the non-heat constitution subjects, this work suggests that blood vessels of these subjects may be more relaxed than that of the heat constitution ones. Stroke volume increased and pulse pressure decreased in the non-heat constitution subjects after taking aged ginger tea, which may elevate arterial compliance corresponding to maintaining an estimated radial-arterial diameter in our study. However, the percussion wave widened and the valley increased in the heat constitution subjects after taking aged ginger tea. This corresponds to the markedly reduced radial-arterial diameter, indicating tighter blood vessels than the baseline status. Accordingly, this study confirms that selecting foods with attributes opposite to personal constitutions is important for reestablishing a healthy cold-heat balance within the human body. Moreover, novel noninvasive sphygmography may be a useful instrument to classify scientifically the heat personal constitution and the responses to different attribute foods.

The purpose of the present study was to investigate effect of electro-acupuncture (EA) at different frequencies on autonomic function. Twenty healthy adult volunteers were studied, and underwent 4 sessions of EA (sham, 2 Hz, 15 Hz, and 50 Hz). Sham, 2 Hz, 15 Hz, and 50 Hz EA was applied to the bilateral Leg Three Li (??? zú san li, ST-36) and Upper Great Hollow (??? shàng jù xu, ST-37) acupoints. The intensity of electrical stimulation was adjusted to obtain visible twitching of the anterior tibial muscle about 2.0-2.5 mA except sham without electrical stimulation. The components of heart rate variability (HRV) and blood pressure were measured before EA (BLP), EA (EAP), and post-EA periods (PEP). The results indicated that the natural logarithmic high frequency power (lnHF) of HRV was greater during PEP than during the BLP in the 2 Hz EA sessions. The natural logarithmic low frequency power (lnLF) of HRV was greater during the PEP than during the BLP in 15 Hz EA sessions, suggesting that 2 Hz EA apply to Leg Three Li (??? zú san li, ST-36) and Upper Great Hollow (??? shàng jù xu, ST-37) acupoints increased vagal activity, whereas 15 Hz EA increased sympathetic activity.

Transcriptomics using DNA microarray has become a practical and popular tool for herbal medicine study because of high throughput, sensitivity, accuracy, specificity, and reproducibility. Therefore, this article focuses on the overview of DNA microarray technology and the application of DNA microarray in Chinese herbal medicine study. To understand the number and the objectives of articles utilizing DNA microarray for herbal medicine study, we surveyed 297 frequently used Chinese medicinal herbs listed in Pharmacopoeia Commission of People's Republic of China. We classified these medicinal herbs into 109 families and then applied PudMed search using "microarray" and individual herbal family as keywords. Although thousands of papers applying DNA microarray in Chinese herbal studies have been published since 1998, most of the articles focus on the elucidation of mechanisms of certain biological effects of herbs. Construction of the bioactivity database containing large-scaled gene expression profiles of quality control herbs can be applied in the future to analyze the biological events induced by herbs, predict the therapeutic potential of herbs, evaluate the safety of herbs, and identify the drug candidate of herbs. Moreover, the linkage of systems biology tools, such as functional genomics, transcriptomics, proteomics, metabolomics, pharmacogenomics and toxicogenomics, will become a new translational platform between Western medicine and Chinese herbal medicine.

Development of anti-severe acute respiratory syndrome associated coronavirus (SARS-CoV) agents is pivotal to prevent the reemergence of the life-threatening disease, SARS. In this study, more than 200 extracts from Chinese medicinal herbs were evaluated for anti-SARS-CoV activities using a cell-based assay that measured SARS-CoV-induced cytopathogenic effect (CPE) in vitro on Vero E6 cells. Six herbal extracts, one each from Gentianae Radix (?? lóng dan; the dried rhizome of Gentiana scabra), Dioscoreae Rhizoma (?? shan yào; the tuber of Dioscorea batatas), Cassiae Semen (??? jué míng zi; the dried seed of Cassia tora) and Loranthi Ramus (??? sang jì sheng; the dried stem, with leaf of Taxillus chinensis) (designated as GSH, DBM, CTH and TCH, respectively), and two from Rhizoma Cibotii (?? gou ji; the dried rhizome of Cibotium barometz) (designated as CBE and CBM), were found to be potent inhibitors of SARS-CoV at concentrations between 25 and 200 µg/ml. The concentrations of the six extracts needed to inhibit 50% of Vero E6 cell proliferation (CC50) and 50% of viral replication (EC50) were determined. The resulting selective index values (SI = CC50/EC50) of the most effective extracts CBE, GSH, DBM, CTH and TCH were > 59.4, > 57.5, > 62.1, > 59.4, and > 92.9, respectively. Among these extracts, CBM and DBM also showed significant inhibition of SARS-CoV 3CL protease activity with IC50 values of 39 µg/ml and 44 µg/ml, respectively. Our findings suggest that these six herbal extracts may have potential as candidates for future development of anti-SARS therapeutics.

Hepatoma is a leading cause of death in the world. SK-Hep-1 and HA22T/VGH cells are poorly differentiated human hepatocellular carcinoma cell lines with invasive and migratory abilities. Agaricus blazei (AB) is a mushroom with many biological effects and active ingredients, and the ethanolic extract of AB fermentation product (AB-pE) was demonstrated to inhibit the growth of hepatoma Hep3B and HepG2 cells in our previous study. In this study, we further investigated the anticancer and anti-invasive abctivities of the AB-pE. Results showed that the AB-pE inhibited the growth of SK-Hep1 and HA22T/VGH cells (with IC50 values of 26.8 and 28.7 µg/mL, respectively) and led cells toward apoptosis after 48 h of treatment. Activation of caspase-3 by AB-pE (12.5~200 µg/mL) in a dose-dependent manner was observed in both cell lines using fluorescence microscopy and flow cytometry. The apoptosis triggered by the AB-pE was regulated by the increased expression of Bax, the activation of caspase-3, caspase-9, and PARP, and the decreased expression of Bcl-2. Additionally, the AB-pE showed the potential ability to inhibit invasion of SK-Hep1 and HA22T/VGH cells according to the results of a Matrigel invasion assay. Our results suggested that the AB-pE may be a further developed for its potential against hepatoma due to its antiproliferative (via apoptosis) and anti-invasive activities in hepatoma cells.

Two new flavonol glucuronides, quercetin 3-O-ß-D-2?-acetylglucuronide (1) and quercetin 3-O-ß-D-2?-acetylglucuronide methyl ester (2), along with four known flavonoids (3-6) were isolated from the whole parts of Rotala rotundifolia. The structures of 1 and 2 were elucidated by application of various spectroscopic methods, including 1D and 2D NMR techniques. Biological evaluation showed that all of isolated flavonoid compounds have potent anti-oxidative activities by DPPH and superoxide anion methods, and kaempferol (3) and quercetin (4) exhibited significant anti-HBV activity assayed by anti-HBsAg production. The HPLC fingerprint with photodiode array detection (HPLC-DAD) for quality control of R. rotundifolia partitioned EtOAc layer was also established.

Gastrodiae Rhizoma, also called chì jiàn (??), gui du yóu (???), or tian má (??) in Chinese, is considered a top grade (?? shàng pin) medicine described to enter liver channel (?? gan jing) in classic literatures of traditional Chinese medicine and has been used for centuries. Many studies investigating its various bioactivities and active compounds have been conducted worldwide. This article reviews these biological activities and details the antidepressant pharmacology of Gastrodiae Rhizoma. Gastrodiae Rhizoma treatment exerts an effective inhibition of diverse diseases and disorders, including convulsion, oxidative stress, mental disorders, amnesia, cardio-cerebral-vascular diseases, and inflammation, among others. The antidepressant effect of Gastrodiae Rhizoma was evaluated in animal models and several mechanisms of activity were found, including the modulation and regulation of monoamine oxidase activity, monoamine concentration and turnover, antioxidatant activity, GABAergic system induction, BDNF induction, neuroprotection and anti-inflammatory activity.

Honey could be considered the most sustainable food produced naturally. It contains sugars, vitamins, minerals and has high anti-oxidant activities. Cancer is on the rise in most countries. Carcinogenesis is a multi-step process and has multi-factorial causes. Among these are low immune status, chronic infection, chronic inflammation, chronic nonhealing ulcers, smoking, obesity etc. Published studies thus far have shown that honey improves immune status, has anti-inflammatory and anti-microbial properties and promotes healing of chronic ulcers and wounds and scavenge toxic free radicals. Recently honey has been shown to have anti-cancer properties in cell cultures and in animal models. The mechanisms suggested include induction of apoptosis, disruption of mitochondrial membrane potential and cell cycle arrest. Though sugar is predominant in honey which itself is thought to be carcinogenic, it is understandable that its beneficial effect as anti-cancer agent raises skeptics. With increasing number of people seeking therapy from nature, this area of research has recently gained attention.

Andrographis paniculata is a traditional Chinese herb and displays diverse biological activities including antioxidation, anti-tumorigenesis, anti-virus, and anti-atherogenesis. In this study, we investigated the up-regulation of ethanolic extract of A. paniculata (APE) on the antioxidant defense in rat livers and whether this enhancement protected against carbon tetrachloride (CCl4)-induced liver damage. Male Sprague-Dawley rats were orally administered (i.g.) 0, 0.75, or 2 g/kg/d APE for 5 d. At d 6, rats were sacrificed and liver tissues were removed. Some animals (n=8) were intraperitoneally injected CCl4 (1 mL/kg, 50% in olive oil) and blood was drawn 24 h after CCl4 treatment. The results showed that APE increased hepatic glutathione (GSH) content and superoxide dismutase, GSH peroxidase, and GSH S-transferase activities in a dose-dependent manner (p 0.05). Results of immunoblotting and RT-PCR revealed that rats treated with APE had higher glutamate cysteine ligase catalytic and modifier subunits, heme oxygenase 1, superoxide dismutase 1, and GSH S-transferase Ya and Yb protein and mRNA expression than those of control rats. Moreover, APE increased Nrf2 nuclear translocation and Nrf2 binding to DNA in rat liver. In the presence of CCl4, APE decreased hepatic thiobarbituric acid-reactive substances production and plasma aspartate aminotransferase and alanine aminotransferase activities. These results suggest that APE protection against CCl4 insult is attributed, at least in part, to its up-regulation of antioxidant defense in rat liver.

Garlic (?? dà suàn; the bulb of Allium sativum), bestowed with an array of organosulfur compounds finds its application in treating many ailments including cardiovascular problems, common cold, bacterial and fungal infections and cancer. Numerous epidemiological evidences document the beneficial effects of various bioactive organosulfur compounds of garlic against different types of cancer. Studies involving the animal and cell models indicate garlic bioactive compounds could be effective in treating all the stages of cancer. This review gives an update on the recent pre-clinical and clinical trials, carried out to evaluate the efficacy of various garlic bioactive compounds along with the mechanism of action pertaining to major digestive cancers including liver, gastric and colorectal cancers. The major anti-carcinogenic mechanisms are caspase dependent and/or independent induction of apoptosis, anti-proliferative, anti-metastasis, anti-oxidant and immunomodulative properties. Form the clinical trials an increase in the garlic consumption of 20 g/day reduced the risk of gastric and colorectal cancer. In summary, increased uptake of garlic in diet may prevent the incidence of digestive cancers.

The protective effect of red mold rice (RMR) against liver injury in rats fed with a Zn-deficient diet for 12 weeks was investigated in this study. Rats were orally administered RMR (151 mg/kg body weight or 755 mg/kg body weight; 1 × dose or 5 × dose, respectively) with or without Zn once a day for 4 consecutive weeks. The severity of liver damage was evaluated by measuring the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in Zn-deficient rats. RMR significantly inhibited the elevation of serum ALT levels by Zn-deficient induction. Hepatic antioxidase activity was also significantly increased in the RMR + Zn group (RZ), thereby suppressing the productions of reactive oxygen species (ROS) and proinflammatory cytokines in the liver of Zn-deficient rats. These findings suggested that RMR exerted hepatoprotective effects against Zn deficiency-induced liver inflammation.

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The effect of allicin, an active ingredient of garlic, on lactate dehydrogenase (LDH) leakage, lipid peroxidation, glutathione (GSH) content, and GSH-related enzyme activity was investigated in primary hepatocytes. In this study, allicin was synthesized in our laboratory as an experimental material, and primary hepatocytes isolated from Sprague-Dawley rats were used as an experimental model. According to the results, hepatocytes treated with 10 µM allicin did not differ from the control on LDH leakage during various incubation times. When the hepatocytes were treated with 10 µM allicin, their levels of thiobarbituric acid reactive-substances (TBARS) did not differ significantly from that of the control within the 8-h incubation. However, the TBARS values of hepatocytes treated with 30 and 50 µM allicin were higher compared to the control after incubation for 4 h and 8 h, respectively. The hepatocyte intracellular GSH content was significantly higher than that of the control after 30 µM allicin treatment, but treatment with 50 µM allicin caused a significant GSH depletion after incubation for 4 h or longer. In addition, when hepatocytes were treated for 24 h with 10 or 30 µM allicin, glutathione peroxidase (GPx) activity was significantly increased compared to that of the control, whereas 50 µM allicin treatment for 24 h or longer significantly decreased the GPx activity. Glutathione reductase (GRd) activity was significantly increased when the hepatocytes were treated with 10 µM allicin for 24 h, but GRd activity significantly decreased when the hepatocytes were treated with 50 µM allicin. However, hepatocytes treated for 24 h with 10 or 30 µM allicin showed significantly increased glutathione S-transferase (GST) activity compared to the control. These results suggest that 10 µM allicin potentially enhances the antioxidation and detoxification capabilities of primary rat hepatocytes.

The aim of this study is to elucidate how the Isatidis Radix (??? ban lán gen) tonic, as an aqueous mixture of hundreds of compositions, interrupts the infection of influenza viruses to their host cells. The efficacy of the tonic was evaluated and expressed as cell proliferation rate and plaque reduction rate in Madin-Darby Canine Kidney (MDCK) cells, against 3 strains of influenza A and B viruses. This boiling water (at 100°C ) extract of Isatidis Radix (RIE) showed antiviral activity against influenza virus A and B. The concentration for 50% inhibition of influenza virus A replication (IC50) in MDCK cell was 12.6 mg/mL with a therapeutic index >8. When cells were incubated with RIE prior to virus dsorption, the numbers of viable cell were at least doubled compared to the numbers of virus control, RIE incubation after virus adsorption and RIE incubation with virus prior to adsorption, in both influenza virus A and B. Moreover, much less virus particles were spotted by scanning electron microscope (SEM) in the RIE pre-treated cells than the cells without RIE treatment. These results indicate the antiviral activity of RIE is mainly attributed to its host cell protection effect but not actions on virus or post-virus-adsorption interruption. Cell, but not virus, is more likely to be the action target of RIE.

Fatigue is a noticeable and highly prevalent symptom in tense, industriously, and economically affluent modern society. Therefore, new antifatigue agents to smooth the fatigue feature are an energetic topic. The total ethanol extract (ESI) of Saussurea involucrata Kar et Kir., known as Tian-Shan snow lotus, was evaluated for antifatigue activity in ICR mice with mice forced swimming test and the determination of the contents of blood lactic acid and serum urea nitrogen. ESI (0.05, 0.15, 0.25 g/kg) was administered orally to mice for 4 weeks. The average swimming times to exhaustion of the ESI-treated ICR mice (0.15, 0.25 g/kg) were prolonged by 132% and 180% (p0.001) with a lessening of fatigue compared with that of the control group. Analysis of biochemical parameters showed that levels of serum urea nitrogen and blood lactic acid of experimental groups were also decreased significantly (p0.001) compared with that of the control group. The antioxidant activity of ESI was investigated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging assay and the hydrogen peroxide-induced luminol chemiluminescence assay and the results indicated that ESI exerts DPPH scavenging ability and reducing power. These results provide scientific evidence that S. involucrata may have been potential as an antifatigue agent.

Bioassay-guided fractionation of the EtOH extract of the dried twigs of Podocarpus nakaii Hayata (Podocarpaceae), endemic plant in Taiwan has resulted in isolation of four [3'?8?]-biflavonoid derivatives, amenotoflavone (AF), podocarpusflavone-A (PF), II-4?,I-7-dimethoxyamentoflavone (DAF), and heveaflavone (HF). Their structures were determined by physical and extensive spectroscopic analyses such as 1H, 13C, 1H-1H COSY, HMQC, and HMBC, as well as comparison with literature values. Compounds PF and DAF showed significant inhibitions against DLD, KB, MCF-7, HEp-2 tumor cell lines (ED50 ca. 4.56-16.24 µg/mL) and induced cell apoptosis in MCF-7 via mainly sub-G1/S phase arrest. Furthermore, these compounds exhibited moderate Topoisomerase I inhibitory activity.

The protective effect of red mold rice (RMR) against liver injury in rats fed with a Zn-deficient diet for 12 weeks was investigated in this study. Rats were orally administered RMR (151 mg/kg body weight or 755 mg/kg body weight; 1 × dose or 5 × dose, respectively) with or without Zn once a day for 4 consecutive weeks. The severity of liver damage was evaluated by measuring the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in Zn-deficient rats. RMR significantly inhibited the elevation of serum ALT levels by Zn-deficient induction. Hepatic antioxidase activity was also significantly increased in the RMR + Zn group (RZ), thereby suppressing the productions of reactive oxygen species (ROS) and proinflammatory cytokines in the liver of Zn-deficient rats. These findings suggested that RMR exerted hepatoprotective effects against Zn deficiency-induced liver inflammation.

There are many challenges to developing an evidence base for Traditional Chinese Medicine and Integrative East-West Medicine. This article offers a review of these challenges alongside an introduction and review of several innovations in healthcare research that have successfully been applied to the study of Traditional Chinese Medicine and Integrative Medicine. Such innovations include developments in Whole Systems Research, Comparative Effectiveness Research, Health Services Research, and qualitative Social Sciences Research. Each of these approaches expands upon conventional approaches to clinical research and can also be combined with clinical trial data to yield a mixed methods approach. We conclude with a commentary on the necessity for such mixed methods studies in the continued establishment of an evidence base for TCM and IM.