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Background: Platycodon grandiflorum is a flowering plant that is used in traditional medicine for treating pulmonary and respiratory disorders. It exerts various pharmacological effects, including immunomodulatory and anti-cancer activities. The purpose of this study was to confirm the in vitro and in vivo immune-enhancing effects of P. grandiflorum extract (PGE) on splenocytes isolated from cyclophosphamide (CP)-induced immunosuppressed rats., Methods: For in vitro analysis, splenocytes were treated with PGE at various doses along with CP. Cell viability was measured by a WST-1 assay, and NK cell activity and cytotoxic T lymphocyte (CTL) activity was also examined. In addition, immunoglobulin A (IgA), IgG, and cytokine levels were measured. For in vivo analysis, Sprague Dawley rats were treated with various doses of PGE along with CP. Complete blood count (CBC) was performed, and plasma levels of IgA, IgG, TNF-α, IFN-γ, IL-2, and IL-12 were quantified. Additionally, tissue damage was assessed through histological analyses of the thymus and spleen., Results: PGE treatment enhanced cell viability and natural killer cell and cytotoxic T lymphocyte activity, and increased the production of CP-induced inflammatory cytokines (TNF-α, IFN-γ, IL-2, and IL-12) and immunoglobulins (IgG and IgA) in splenocytes. In addition, in CP-treated rats, PGE treatment induced the recovery of white blood cell, neutrophil, and lymphocyte counts, along with mid-range absolute counts, and increased the serum levels of inflammatory cytokines (TNF-α, IFN-γ, IL-2, and IL-12) and immunoglobulins (IgG and IgA). Moreover, PGE attenuated CP-induced spleen and thymic damage., Conclusions: Our results confirmed that PGE exerts an immune-enhancing effect both in vitro and in vivo, suggesting that PGE may have applications as a component of immunostimulatory agents or as an ingredient in functional foods.

Rice porridge containing Allium fistulosum (Welsh onion) root water extract (RAFR) has anti-inflammatory bioactive compounds. We examined whether the long-term administration of rice porridge with RAFR would prevent or delay the progression of osteoarthritis and menopausal symptoms in estrogen-deficient animals by ovariectomy. The rats consumed 40% fat energy diets containing 250 mg RAFR (rice: Allium fistulosum root = 13:1)/kg body weight (bw) (OVX-OA-RAFR-Low), 750 mg RAFR/kg bw (OVX-OA-RAFR-High) and 750 mg starch and protein/kg bw(OVX), respectively. After consuming the assigned diets for eight weeks, monoiodoacetate (OVX-OA) or saline (OVX) were injected into the knee joints of the rats for an additional three weeks. Sham rats were administered saline injections (normal-control). OVX-OA-RAFR improved oral glucose tolerance and also protected against decreases in bone mineral density and lean body mass in the legs and increases in fat mass in the abdomen, compared to the OVX and OVX-OA. OVX-OA-RAFR improved swelling and limping scores, normalized weight distribution between the osteoarthritic and normal limbs, and increased maximum running speeds compared to the OVX-OA. The OVX-OA deteriorated the articular cartilage by reducing the articular matrix and bone loss in the knee joint and it prevented knee joint deterioration when compared to the OVX. The improvement in osteoarthritis symptoms in OVX-OA-RAFR decreased the mRNA expression of matrix metallo-proteinase-1 and matrix metalloproteinase-13, tumor necrosis factor-α, and interleukin-1β and interleukin-6 in the articular cartilage compared to OVX-OA rats. In conclusions, RAFR is effective in treating osteoarthritis symptoms and it may be used for a therapeutic agent in osteoarthritis-induced menopausal women.

In this study, we evaluated the immunity-enhancing effects of Orostachys japonicus A. Berger (OJ). To examine the immune protective effect in vitro, primary mouse splenocytes were treated with water or ethanol extracts of OJ in the absence or presence of cyclophosphamide (CY), which is a cytotoxic, immunosuppressive agent. The extracts increased the propagation of splenocytes and inhibited CY-induced cytotoxicity. Further, to examine the immunostimulatory effects in vivo , adult Wistar rats were orally administered OJ extracts with or without CY treatment. With the administration of OJ extracts, CY-treated immunosuppressed rats showed improved physical endurance, as assessed by the forced swim test. In addition, extract administration increased not only the number of immunity-related cells but also the levels of plasma cytokines. OJ extracts also recovered splenic histology in CY-treated rats. These findings suggest that an OJ regimen can enhance immunity by increasing immune cell propagation and specific plasma cytokine levels.

Red mulberry (Morus alba) fruit is rich in anthocyanins, and mulberry leaves are used by silk worms to make silk protein. We determined that the water and ethanol extract of mulberry fruit and silk amino acids accelerated ethanol degradation and suppressed temporal cognitive dysfunction in acute alcohol administered rats. The mechanism was explored in rats with acute oral administration of silk protein and mulberry fruit extracts. Rats were given 0.3 g of dextrin (control) and water extract (WMB) and ethanol extract of mulberry (EMB), silk protein hydrolysates (SKA), and a commercial product (positive‑control) based on body weight. After 30 min, rats were administered 3 g ethanol/kg body weight and serum ethanol and acetaldehyde levels were measured. After 3 h movements were measured with a video tracking system and at 5 h cognitive function was measured by Y maze test. WMB contain much higher rutin, luteolin and quercetins than EMB. In SKA rats, serum alcohol concentrations slowly increased until 60 min, but were markedly elevated until 120 min. However, WMB rats exhibited rapidly increased serum alcohol levels until 60 min and showed the lowest peak of serum alcohol levels, indicating the highest degradation of alcohol. The patterns of serum acetaldehyde levels were similar to those of serum ethanol levels but WMB was more effective for reducing serum acetaldehyde levels than serum ethanol levels. WMB was most effective for increasing mRNA expression of alcohol dehydrogenase and acetaldehyde dehydrogenase. WMB and SKA decreased lipid peroxides by increasing activities of SOD and GSH‑Px in the liver and they also reduced pro‑inflammatory cytokines such as tumor necrosis factor‑α and interleukin‑6. WMB and SKA exerted better anti‑oxidant effects than the positive‑control. WMB containing higher flavonoids reduced pro‑inflammatory cytokines better than SKA. In conclusions, both WMB and SKA might reduce acute alcohol‑induced hangover and liver and brain damage by lowering serum alcohol and acetaldehyde levels.

Ethnopharmacological Relevance: Taraxacum coreanum Nakai has been traditionally used for treating inflammatory diseases including gastrointestinal diseases., Aim of the Study: We studied whether water extracts of Taraxacum coreanum Nakai (TCN) had a protective effect on acute and chronic gastritis induced by ethanol/HCl in an animal model of gastritis and its mechanism was also explored., Materials and Methods: In the acute study, rats were orally administered 0.15g/mL dextrin (normal-control), 0.15g/mL dextrin (control), 0.05g/mL TCN (TCN-L), 0.15g/mL TCN (TCN-H), or 0.01g/mL omeprazole (orally; positive-control), followed by oral administration of 1mL of 60% ethanol plus 150mM HCl (inducer). In the chronic study, rats were administered 10% diluted inducer in drinking water, and 0.6% dextrin, 0.2% or 0.6% TCN, and 0.05% omeprazole were administered in chow for 4 weeks. Acid content, gastric structure, oxidative stress, and markers of inflammation in the stomach tissue were measured at the end of experiment., Results: Acute and chronic ethanol/HCl administration caused the inner layer of the stomach to redden, hemorrhage, and edema in the control group; TCN-H reduced these symptoms more effectively than did the omeprazole positive-control. Acid production and total acidity in the stomach increased in the control group, which was markedly suppressed by omeprazole. TCN also reduced the acid production and acidity, but not to the same degree as omeprazole. H-E and PAS staining revealed that in the inner layer of the stomach, cellular structure was disrupted, with an increased nuclear size and thickness, disarrangement, and decreased mucin in the control group. TCN prevented the cellular disruption in the inner layer, and TCN-H was more effective than the positive-control. This was associated with oxidative stress and inflammation. TCN dose-dependently reduced the infiltration of mast cells and TNF-α expression in the inner layer of the stomach, and decreased lipid peroxides by increasing superoxide dismutase and glutathione peroxidase expression., Conclusions: TCN-H acutely and chronically protected against gastritis and gastric ulcer by reducing oxidative stress and inflammation, not by completely suppressing gastric acid production., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: The root of Saussurea costus (Aucklandia lappa Decne, Aucklandiae Radix, SC) and Thuja orientalis L. (TOL) have been traditionally used as anti-inflammatory agents in Korea. However, they have not been studied for the efficacy of atopic dermatitis (AD) treatment, a chronic inflammatory skin disease. We investigated the efficacy of topical applications with 1,3-butyleneglycol extracts of SC and TOL to alleviate the symptoms of AD., Materials and Methods: HaCaT cells and the dorsal skin of Nc/Nga mice had a local exposure of house mite extracts and 2,4-dinitrochlorobenzene (DNCB), respectively. After lesions developed, we topically applied 1,3-butylen glycol (vehicle; control), SC (30%), TOL (30%), or SC (15%)+TOL (15%) to the skin lesions for 5 weeks. The normal-control was not exposed to DNCB. The skin thickness, mast cell infiltration, serum immunoglobulin E (IgE) and IgG1 and gene expressions of interleukin (IL)-4, IL-13, and IFN-γ in the dorsal skin and HaCaT cells were measured., Results: Chlorogenic acid (129.6±10.2μg/g) for SC and catechin and apigenin (93.4±13.2 and 16.9±1.3μg/g, respectively) for TOL were used as indicator compounds for the strength of the extracts. SC+TOL decreased the expression of protease-activated receptor-2 and ICAM-1 and the release of TNF-α and IL-6 in HaCaT cells activated by 3μg/mL house mite extracts in comparison to either of SC or TOL alone. In Nc/Nga mice challenged with DNCB, SC+TOL synergistically attenuated clinical symptoms of AD such as erythema, hemorrhage, edema, excoriation and dryness in the dorsal skin better than either SC or TOL alone. Histological analysis of the dorsal skin also showed that SC+TOL treatment significantly and additively decreased the inflammatory cellular infiltrate, including mast cells and eosinophils in comparison to either of SC or TOL. SC+TOL also decreased serum IgE and IgG1 levels and the expression of IFN-γ, IL-4, and IL-13 mRNA in dorsal skin in DNCB-treated Nc/Nga mice., Conclusion: SC+TOL relieved the symptoms of AD by reducing pro-inflammatory activity and over-activated immune responses. These data suggest that SC+TOL may be an effective alternative intervention for the management of AD., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: Artemisia princeps Pamp (APP), Leonurus japonicas Houtt (LJH), and Gardenia jasminoides Ellis fruit (GJE) have been traditionally used in East Asia to treat women's diseases related to reproductive system. They may attenuate the deterioration of energy, lipid, glucose and bone metabolism by estrogen deficiency. The present study explored the combination of APP, LJH, and GJE to overcome the symptoms of estrogen deficiency and the mechanism was explored., Methods: Ovariectomized (OVX) rats were divided into five groups and fed high-fat diets supplemented with 2 % dextrin (control), 2 % APP, 2 % APP + LJH (15:5), APP + LJH + GJE (10:5:5) or 17β-estradiol (30 μg/kg bw/day) for 8 weeks. After 8 weeks of their consumption, energy, lipid, glucose and bone metabolisms were investigated and hepatic insulin signaling and fatty acid metabolism were determined., Results: APP + LJH + GJE, but not APP itself, improved energy metabolism and attenuated a decrease in energy expenditure by the same amount as estrogen. Moreover, APP + LJH + GJE reduced visceral fat and intramuscular fat and increased lean body mass measured by DEXA by as much as the positive-control. APP itself suppressed increased LDL cholesterol and triglyceride levels in OVX rats and APP + LJH + GJE alleviated dyslipidemia in OVX rats. Overnight-fasted serum insulin levels and HOMA-IR were reduced in the descending order of APP, APP + LJH, APP + LJH + GJE, positive-control in OVX rats. APP and APP + LJH elevated insulin secretion in the 1st part of OGTT to decrease serum glucose levels while APP + LJH + GJE reduced serum glucose levels without increasing serum insulin levels during OGTT. APP + LJH + GJE decreased insulin resistance during ITT in OVX rats more than the positive-control. The APP + LJH + GJE group exhibited increased hepatic peroxisomal proliferator-activated receptor-γ coactivator-1α expression, which increased the number of genes involved in fatty acid oxidation and decreased fatty acid synthesis. Hepatic insulin signaling (pAkt and pGSK-1β) was also potentiated to reduce phosphoenolpyruvate carboxykinase proteins., Conclusion: The combination of APP + LJH + GJE attenuated various menopausal symptoms in OVX rats. Thus, it may have potential as a therapeutic agent for the treatment of postmenopausal symptoms.

The brain is an important modulator of glucose metabolism, and is known to respond Gastrodia elata Blume water extract (GEB). Therefore, we examined whether long-term administration of GEB has hypoglycemic activity, and its action mechanism was explored in partially-pancreatectomized rats that exhibit similar characteristics as Asian type 2 diabetes, non-obese insulin-insufficient diabetes. The rats were provided high-fat diets supplemented with either of (1) 0.5% GEB (GEB-L), (2) 2% GEB (GEB-H), (3) 2% dextrin (control), or (4) 2% dextrin with rosiglitazone (20 mg/kg body weight; positive-control) for eight weeks. GEB dose-dependently improved hypothalamic insulin signaling, enhanced whole-body insulin sensitivity during hyperinsulinemic euglycemic clamp, and reduced hepatic glucose output in a hyperinsulinemic state. GEB dose-dependently increased the area under the curve of the serum insulin levels at the first and second phases during hyperglycemic clamp compared to the control, whereas the positive control had no effect. Insulin sensitivity during the hyperglycemic state also improved, dose-dependently, in response to GEB compared with that of the control, but was less than the positive control. GEB-H increased the mass of β-cells by potentiating proliferation and decreasing apoptosis. In conclusion, GEB could be a therapeutic agent for treating Asian type 2 diabetes.

Objective: We investigated whether long-term consumption of Korean mistletoe or Asian Ulmi cortex would prevent or delay menopausal symptoms and progression of osteoarthritis in estrogen-deficient obese rats., Methods: Ovariectomized (OVX) rats were provided a 45% fat diet containing either (1) 0.6% lyophilized water extract of Korean mistletoe (KME) + 1.4% dextrose (KME; n = 10), (2) 2% lyophilized water extract of Ulmi cortex (UCE; n = 10), (3) 30 μg/kg bw 17β-estradiol + 2% dextrose (positive control; n = 10), (4) 2% dextrose (placebo; OVX-control; n = 10), or (5) 2% dextrose (normal-control; n = 10) for 4 weeks. At the beginning of the 5th week, OVX rats, except in the normal-control group, were given articular injections of monoiodoacetate into the right knee and the assigned diets were provided for an additional 3 weeks. The rats in the normal-control had injections of saline into the right knee., Results: KME, but not UCE, partially prevented the insulin resistance and the loss of bone mineral density and lean mass. The limping scores were lower in the descending order of the OVX-control > KME and 17β-estradiol > UCE > normal-control at day 14 and 21 (P < 0.05). The scores for pain behaviors measured by weight distribution on the right leg, maximum running velocity on a treadmill and locomotive activity, were markedly decreased in the same order as limping scores. Monoiodoacetate increased the expression of matrix metalloprotinase-3 and metalloprotinase-13 in the articular cartilage and elevated the production of inflammatory markers such as tumor necrosis factor-α, interleukin-1β, and interleukin-6, but they were lower in the UCE than in the other groups (P < 0.05). Histology of the right knee revealed cartilage damage near the tidemark of the knee and proteoglycan loss was markedly less in UCE., Conclusions: UCE was an effective therapeutic agent for preventing osteoarthritis and KME prevented decreases in lean body mass, bone mineral density, and insulin sensitivity in estrogen-deficient rats.

Objectives: Methyl jasmolate (MeJA)-treated vegetables produce higher concentrations of various bioactive compounds. We investigated whether long-term oral consumption of MeJA-treated and untreated buckwheat sprout powder improves energy, glucose, lipid, and bone metabolism induced by estrogen deficiency in ovariectomized (OVX) rats fed high-fat diets, and explored the mechanisms involved., Methods: OVX rats were divided into four groups and fed high-fat diets supplemented with 3% dextrin (OVX-control), buckwheat sprout powder (BWS), or MeJA-treated buckwheat sprout powder (MJ-BWS) for 12 wk. Sham rats without estrogen deficiency had a control diet as a normal-control., Results: MeJA-treatment increased total polyphenols and flavonoids by about 1.6 fold and isoorientin, orientin, rutin, and vitexin were elevated by about 18% in buckwheat. After 12 wk, OVX rats exhibited increased weight gain, fat mass, skin temperature, hyperglycemia, and decreased bone mineral density (BMD) compared to sham rats. BWS prevented the increase of skin temperature and decrease of femur BMD, but did not improve energy glucose homeostasis as much as MJ-BWS. MJ-BWS prevented increases in body weight and fat mass. Energy expenditure was lowest in OVX-control, followed by BWS, MJ-BWS, and normal-control. Furthermore, MJ-BWS exhibited greater improvements in glucose and insulin tolerance than OVX-control and BWS. Phosphorylation of hepatic Akt and AMPK was potentiated, in ascending order of OVX-control, BWS, MJ-BWS, and normal-control, whereas PEPCK expression was decreased., Conclusions: MJ-BWS prevented and ameliorated the disturbances in energy and glucose metabolism in estrogen-deficient animals better than BWS. Therefore, besides flavonoids in BWS, other components such as phytoalexins produced in MJ-BWS during MeJA-treatment might play a crucial role in the improvement., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Orostachys japonicus A. Berger (Crassulaceae) (OJ), well-known as Wa-song in Korea is a medicinal plant with immunoregulatory, anti-febrile, antidote, and anti-cancer activities. This study was aimed at evaluating the immunostimulatory effect of O. japonicus A. Berger and its possible mechanisms of action., Materials and Methods: To evaluate the effect of OJ aqueous extract on macrophage activity, we evaluated the modulation of macrophage activation state by observing structural (phagocytic activities) and the production of nitric oxide increase. The effect of OJ aqueous extract on RAW264.7 cell viability were assessed using Cell Counting Kit (CCK)-8 assay. HPLC analysis was performed to identify potential active compounds of this extract., Results: The biological investigations indicated that OJ aqueous extract, among others, possessed the highest macrophage activation as indicated by NO production yield. The results showed that OJ aqueous extract exhibited antioxidant effects, which included scavenging activities against DPPH radicals. OJ aqueous extract increased the phagocytic activity of RAW 264.7 cells against IgG-opsonized red blood cells (RBC). The level of phosphorylated Syk kinase was increased in OJ aqueous extract-treated group as compared to control. Phosphorylation of PLC-γ was increased in the OJ aqueous extract-treated groups. Quercetin-3-O-rhamnose and kaempferol-3-O-rhamnose was detected in OJ aqueous extract by HPLC analysis., Conclusions: OJ aqueous extract might play a pivotal ethnopharmacologic role as an immunostimulatory agent by promoting Fc gamma receptor (FcγR)-mediated phagocytosis of IgG-opsonized RBCs. On the basis of our results, OJ aqueous extract can enhance innate immunity and may serve as an adjuvant for tumor treatment., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The purpose of this study is to investigate the effects of euphorbiasteroid, a component of Euphorbia lathyris L., on adipogenesis of 3T3-L1 pre-adipocytes and its underlying mechanisms. Euphorbiasteroid decreased differentiation of 3T3-L1 cells via reduction of intracellular triglyceride (TG) accumulation at concentrations of 25 and 50 μM. In addition, euphorbiasteroid altered the key regulator proteins of adipogenesis in the early stage of adipocyte differentiation by increasing the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. Subsequently, levels of adipogenic proteins, including fatty acid synthase, peroxisome proliferator-activated receptor-γ and CCAAT/enhancer-binding protein α, were decreased by euphorbiasteroid treatment at the late stage of adipocyte differentiation. The anti-adipogenic effect of euphorbiasteroid may be derived from inhibition of early stage of adipocyte differentiation. Taken together, euphorbiasteroid inhibits adipogenesis of 3T3-L1 cells through activation of the AMPK pathway. Therefore, euphorbiasteroid and its source plant, E. lathyris L., could possibly be one of the fascinating anti-obesity agent., (Copyright © 2015 John Wiley & Sons, Ltd.)

Since Korean mistletoe (Viscum album) has been used for alleviating metabolic diseases, it may also prevent the impairment of energy, glucose, lipid, and bone metabolisms in an estrogen-deficient animal model. We determined that long-term consumption of Korean mistletoe water extract (KME) can alleviate menopausal symptoms such as hot flush, increased abdominal fat mass, dyslipidemia, hyperglycemia, and decreased bone mineral density in ovariectomized (OVX) rats fed a high-fat diet, and explored the mechanisms of the effects. OVX rats were divided into four groups and fed high-fat diets supplemented with either 0.6% dextrin (control), 0.2% lyophilized KME + 0.4% dextrin (KME-L), or 0.6% lyophilized KME (KME-H). Sham rats were fed with the high-fat diets with 0.6% dextrin as a normal-control without estrogen deficiency. After eight weeks, OVX rats exhibited impaired energy, glucose and lipid metabolism, and decreased uterine and bone masses. KME-L did not alleviate energy dysfunction. However, KME-H lowered serum levels of total-, LDL-cholesterol, and triglycerides and elevated serum HDL-cholesterol levels in OVX rats with dyslipidemia, to similar levels as normal-control rats. Furthermore, KME-H improved HOMA-IR, an indicator of insulin resistance, in OVX rats. Surprisingly, KME-H fed rats had greater lean mass in the abdomen and leg without differences in fat mass but neither dosage of KME altered bone mineral density in the lumbar spine and femur. The increased lean mass was related to greater phosphorylation of mTOR and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) in the quadriceps muscles. Hepatic triglyceride contents were lowered with KME-H in OVX rats by increasing carnitine palmitoyltransferase-1 (CPT-1) expression and decreasing fatty acid synthase (FAS) and sterol regulatory element-binding protein-1c (SREBP-1c) expression. In conclusion, KME may be useful for preventing some menopausal symptoms such as hot flushes, dyslipidemia, hepatic steatosis, and loss of muscle mass in post-menopausal women., (© 2014 by the Society for Experimental Biology and Medicine.)

In this study, we performed in vitro and in vivo studies to examine whether a 70% ethanol extract of Prunus mume fruits (EMS) exhibits anti-diabetic effects. Treatment with EMS increased glucose uptake in C2C12 myotubes, and also increased PPAR-γ activity or PPAR-γ mRNA expression. To confirm these in vitro results, we next conducted an animal experiment. A high-fat diet significantly increased the body weight, fat accumulation, and glucose levels in mice. Under the same conditions, 5% EMS attenuated the high-fat diet-induced increase in body weight and fat accumulation and improved the impaired fasting glucose level and glucose tolerance. High performance liquid chromatography analysis demonstrated that EMS contained chlorogenic acid, caffeic acid, rutin, luteolin-7-glucoside, naringin, apigenin-7-glucoside, and hesperidin. Taken together, these findings suggest that EMS exerts an anti-diabetic effect both in vitro and in vivo, which is mediated, at least in part, by the activation of PPAR-γ., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The purpose of this study is to determine the protective effect of Taraxacum official (dandelion) leaf extract (DLE) on high-fat-diet (HFD)-induced hepatic steatosis, and elucidate the molecular mechanisms behind its effects. To determine the hepatoprotective effect of DLE, we fed C57BL/6 mice with normal chow diet (NCD), high-fat diet (HFD), HFD supplemented with 2g/kg DLE DLE (DL), and HFD supplemented with 5 g/kg DLE (DH). We found that the HFD supplemented by DLE dramatically reduced hepatic lipid accumulation compared to HFD alone. Body and liver weights of the DL and DH groups were significantly lesser than those of the HFD group, and DLE supplementation dramatically suppressed triglyceride (TG), total cholesterol (TC), insulin, fasting glucose level in serum, and Homeostatic Model Assessment Insulin Resistance (HOMA-IR) induced by HFD. In addition, DLE treatment significantly increased activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) in liver and muscle protein. DLE significantly suppressed lipid accumulation in the liver, reduced insulin resistance, and lipid in HFD-fed C57BL/6 mice via the AMPK pathway. These results indicate that the DLE may represent a promising approach for the prevention and treatment of obesity-related nonalcoholic fatty liver disease., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Our preliminary study revealed that dementia induced by β-amyloid accumulation impairs peripheral glucose homeostasis (unpublished). We therefore evaluated whether long-term oral consumption of yuzu (Citrus junos Tanaka) extract improves cognitive dysfunction and glucose homeostasis in β-amyloid-induced rats. Male rats received hippocampal CA1 infusions of β-amyloid (25-35) [plaque forming β-amyloid; Alzheimer disease (AD)] or β-amyloid (35-25) [non-plaque forming β-amyloid; C (non-Alzheimer disease control)] at a rate of 3.6 nmol/d for 14 d. AD rats were divided into 2 dietary groups that received either 3% lyophilized 70% ethanol extracts of yuzu (AD-Y) or 3% dextrin (AD-C) in high-fat diets (43% energy as fat). The AD-C group exhibited greater hippocampal β-amyloid deposition, which was not detected in the C group, and attenuated hippocampal insulin signaling. Yuzu treatment prevented β-amyloid accumulation, increased tau phosphorylation, and attenuated hippocampal insulin signaling observed in AD-C rats. Consistent with β-amyloid accumulation, the AD-C rats experienced cognitive dysfunction, which was prevented by yuzu. AD-C rats gained less weight than did C rats due to decreased feed consumption, and yuzu treatment prevented the decrease in feed consumption. Serum glucose concentrations were higher in AD-C than in C rats at 40-120 min after glucose loading during an oral-glucose-tolerance test, but not at 0-40 min. Serum insulin concentrations were highly elevated in AD-C rats but not enough to lower serum glucose to normal concentrations, indicating that rats in the AD-C group had insulin resistance and a borderline diabetic state. Although AD-C rats were profoundly insulin resistant, AD-Y rats exhibited normal first and second phases of glucose tolerance and insulin sensitivity and secretion. In conclusion, yuzu treatment prevented the cognitive dysfunction and impaired energy and glucose homeostasis induced by β-amyloid infusion.

As malfunction/absence of immune cells causes a variety of immunosuppressive disorders and chemical synthetic drugs for curing these diseases have many adverse effects, vigorous studies are being conducted. The Acanthopanax family has been used as traditional medicines for gastric ulcer, diabetes, etc. and culinary materials in East-South Asia. In this study, the immunostimulating properties of A. sessiliflorus were evaluated. A. sessiliflorus increased not only the splenocyte number but also immune-related cytokines such as TNF-α. However, it could not upregulate the expressions of IFN-γ and IL-2. A. sessiliflorus increased the swimming time, and comparison of organ weights relative to body weights for immune-related organs such as the spleen and thymus after a forced swim test showed that it could recover the spleen and thymus weights. It also increased the expression of TNF-α and slightly increased the concentration of IFN-γ but not IL-2. From the results, we concluded that as A. sessiliflorus has not only a host defense effect but also a stress-ameliorating property, further study it will be a promising material of immunostimulating material.

We investigated the hepatoprotective effects of the extract of dandelion leaves (EDL) on a murine model of methionine- and choline-deficient (MCD) diet-induced nonalcoholic steatohepatitis (NASH). C57BL/6 mice were fed for 4 weeks with one of the following diets: control diet (Cont), MCD diet (MCD), MCD diet supplemented with EDL at 200 mg/kg body weight·daily (MCD+D200), and MCD diet supplemented with EDL at 500 mg/kg body weight·daily (MCD+D500). Hepatic function was assessed by evaluating the following parameters: liver histology; plasma levels of alanine aminotransferase (ALT), triglyceride (TG), malondialdehyde (MDA), and reduced glutathione (GSH); expression levels of TNF-α and IL-6; and levels of caspase-3 and pJNK/JNK protein. Histopathological evaluations revealed that addition of EDL to the MCD diet dampens the severity of the clinical signs of NASH. Moreover, EDL led to a significant decrease in the serum levels of ALT, hepatic TG, and MDA, and in the expression levels of TNF-α, and IL-6; on the contrary, the levels of reduced GSH increased. At the post-transcriptional level, EDL significantly decreased the activation of procaspase-3 to active caspase-3, and the phosphorylation of JNK. These results suggest that the beneficial effects of EDL on NASH are mainly due to its antioxidant and anti-inflammatory activities.

Background: Previous research demonstrated that the crude saponins of Platycodi radix improve glucose metabolism by enhancing insulin sensitivity in type 2 diabetic animals; however, which individual saponins are the most potent insulin sensitizers is unknown., Objectives: This study investigated which saponin(s) have anti-diabetic action in vitro and in vivo., Methods: The insulin-stimulated glucose uptake and PPAR-γ agonistic actions of six saponins from Platycodi radix were investigated in 3T3-L1 adipocytes, and glucose-stimulated insulin secretion was determined in Min6 cells. Four individual saponins (20 mg/kg body weight) were orally administered to low-dose streptozotocin-injected diabetic mice fed a high-fat diet for 8 weeks to evaluate glucose tolerance by oral glucose tolerance testing (OGTT), insulin sensitivity by insulin tolerance testing, and insulin signaling in the liver and adipose tissues., Results: Platyconic acid (PA) most effectively increased insulin-stimulated glucose uptake in 3T3-L1 adipocytes, possibly in part by working as a peroxisome proliferator-activated receptors (PPAR)-γ activator; however, none of the saponins improved glucose-stimulated insulin secretion in insulinoma cells. PA-treated diabetic mice exhibited the lowest peak serum glucose levels and highest serum insulin levels during the first part of OGTT. PA also improved insulin sensitivity: PA increased glycogen accumulation and decreased triacylglycerol storage in liver, which was associated with enhanced hepatic insulin signaling, while PA potentiated the expression of adiponectin and PPAR-γ in adipose tissue, and improved insulin signaling and increased GLUT4 translocation into the membranes., Conclusions: PA improves glucose homeostasis in type 2 diabetic mice, partly by enhancing hepatic and adipocyte insulin sensitivity, possibly by activating PPAR-γ.

Background: Standardized Korean red ginseng extract has become the best-selling influenza-like illness (ILI) remedy in Korea, yet much controversy regarding the efficacy of the Korean red ginseng (KRG) in reducing ILI incidence remains. The aim of the study is to assess the efficacy of the KRG extract on the ILI incidence in healthy adults., Methods/design: We will conduct a randomized, double-blind, placebo-controlled study at the onset of the influenza seasons. A total of 100 subjects 30-70 years of age will be recruited from the general populations. The subjects will be instructed to take 9 capsules per day of either the KRG extract or a placebo for a period of 3 months. The primary outcome measure is to assess the frequency of ILI onset in participated subjects. Secondary variable measures will be included severity and duration of ILI symptoms. The ILI symptoms will be scored by subjects using a 4-point scale., Discussion: This study is a randomized placebo controlled trial to evaluate the efficacy of the KRG extract compared to placebo and will be provided valuable new information about the clinical and physiological effects of the KRG extract on reduction of ILI incidence including flu and upper respiratory tract infections. The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if KRG extract can be shown to be an effective reduction strategy in ILI incidence., Trial Registration: NCT01478009.

Ethnopharmacological Relevance: Fructus Schisandrae, the fruit of Schisandra chinensis (Turcz.) Baillon, has been traditionally used as a hypoglycemic agent in Asia and its extracts have been shown to improve insulin-stimulated glucose uptake in cell-based assays in previous studies., Aim of the Study: We set out to determine which fractions of Fructus Schisandrae improved peroxisome proliferator-activated receptor (PPAR)-γ activity and glucose-stimulated insulin secretion in cell-based experiments. The fractions that enhance glucose homeostasis were then tested for their hypoglycemic effects and mechanism was examined., Materials and Methods: The fractions (FS-0, FS-20, FS-40, FS-60, FS-80, FS-100) were made by extracting Fructus Schisandrae with 70% ethanol followed by its fractionation with a XDA column with a different ratio of methanol and water. The insulin-stimulated glucose uptake and PPAR-γ agonistic actions of each fraction were investigated in 3T3-L1 adipocytes and glucose-stimulated insulin secretion was determined in Min6 cells. The fraction(s) that were efficacious (200mg/kg bw) were orally given to 90% pancreatectomized (Px) diabetic rats for 8 weeks to evaluate insulin sensitivity in euglycemic hyperinsulinemic clamp and insulin secretion at hyperglycemic clamp., Results: FS-60 contains schizandrin, gomisin A and angeloylgomisin H while FS-80 contains deoxyschizandrin, γ-schizandrin, and gomisin N. A PPAR-γ agonistic action was greater in the ascending order of the control, FS-80 and FS-60 in 3T3-L1 adipocytes. FS-60 increased the glucose disposal rates of Px rats as much as rosiglitazone during euglycemic hyperinsulinemic clamp while hepatic glucose output at hyperinsulinemic clamped states decreased in the descending order of the control, FS-80, FS-60 with potentiating insulin signaling. At hyperglycemic clamp only FS-60 potentiated first phase insulin secretion in diabetic animals; the second phase was not increased., Conclusions: FS-60, a lignan-rich fraction, improves glucose homeostasis by increasing glucose disposal rates and enhancing hepatic insulin sensitivity by working as a PPAR-γ agonist in type-2 diabetic rats., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Panax ginseng and its major component, ginsenosides, are widely used for the prevention of various disorders in oriental medicine., Aim of the Study: To evaluate the effect of ginsenoside Rc (Rc), one of the active constituents in Panax ginseng, on glucose uptake in C2C12 myotubes., Results: Treatment of the C2C12 myotubes with Rc significantly increased glucose uptake. To determine the mechanism of Rc-induced glucose uptake, either insulin-dependent signaling or insulin-independent signaling pathway activities were measured using western blot analysis. We showed that Rc significantly activated an insulin-independent AMPK signaling pathway. However, Rc had no effect on the components of the insulin-dependent signaling pathway, such as receptor substrates (IRS)-1 and protein kinase B or Akt (PKB/Akt). Moreover, we found that treatment with an AMPK inhibitor abolished both glucose uptake and p38 MAPK phosphorylation. This result implies that AMPK activity is critical for the Rc-induced glucose uptake and that AMPK is situated upstream of p38 MAPK. In addition, we also showed that the activation of AMPK and p38 induced by ginsenoside Rc is mediated by reactive oxygen species (ROS) production, suggesting that upstream regulators of AMPK- and p38 MAPK-mediated glucose uptake., Conclusion: Ginsenoside Rc significantly enhances glucose uptake by inducing ROS generation, which leads to AMPK and p38 MAPK activation. Consequently, ginsenoside Rc can be used as a potent natural anti-diabetic agent., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Complex oil of Zanthoxylum schinifolium and Perilla frutescens seed (ZPCO) is used as a traditional medicine due to its pharmacological activities. The aim of this study was to investigate the immunostimulatory effect of ZPCO in isolated splenocytes as well as in an immunosuppressed rat model, which was generated via oral administration of cyclophosphamide. Notably, our results showed that ZPCO exerted an immunity-enhancing effect both in vitro and in vivo. Specifically, ZPCO treatment enhanced the viability and inflammatory cytokine production of splenocytes and NK cell activity in vitro. Moreover, this product improved host defense under immunosuppressive conditions by increasing the number of immune cells and promoting the expression of cytokines involved in immune responses. Our results suggest that complex oil including Z. schinifolium should be explored as a novel immunostimulatory agent that could potentially be used for therapeutic purposes or as an ingredient in functional foods. [ABSTRACT FROM AUTHOR]