An Aluminosilicate Zeolite Containing Rings of Tetrahedral Atoms with All Odd Numbers from Five to Eleven.

Herein we report the synthesis, structure solution, and catalytic properties of PST-31, which has an unprecedented framework topology. This high-silica (Si/Al=16) zeolite was synthesized using a pyrazolium-based dication with a tetramethylene linker as an organic structure-directing agent (OSDA) in hydroxide media. The PST-31 structure is built from new building layers containing four-, five-, six-, and seven-membered rings, which are connected by single four-membered rings in the interlayer region to form a two-dimensional pore system. Its channels consist of [4.56 .6.9.11] and [5.6.7.9.10.11] cavities and are thus delimited by nine-, ten-, and eleven-membered rings. The OSDA cations in as-synthesized PST-31 were determined to reside without disorder in the large [42 .514 .64 .72 .94 ] cavities composed of smaller [4.56 .6.9.11] and [5.6.7.9.10.11] ones, leading to a symmetry coincidence between the OSDA and the surrounding zeolite cavity. The proton form of PST-31 was found to be selective for the cracking of n-hexane to light olefins.

Effects of spicatoside A isolated from the tuberous roots of Liriope platyphylla on ovalbumin-induced asthma in mice.

The tuberous roots of Liriope platyphylla (Liriopis Tuber; LT) is traditionally used in Korean Medicine for treating colds, cough, and sputum production. In this study, we investigated the effect of spicatoside A isolated from LT methanol extract on ovalbumin (OVA)-sensitized/challenged asthmatic mice. For induction of allergic asthma, BALB/c mice were sensitized with OVA by an intraperitoneal injection at three times a week, and then challenged into the nasal cavities using a nebulizer. Spicatoside A at dose of 1mg/kg body weight was treated in mice with an oral administration once daily for a week during OVA challenge. The concentrations of OVA-specific IgE, IL-4, IL-5 and IL-13 were measured in the sera or bronchoalveolar lavage fluids (BALF) of mice by enzyme-linked immunosorbent assay (ELISA). The numbers of total cells, macrophages, lymphocytes, neutrophils and eosinophils were counted in BALFs using Diff-Quik staining, and histopathological changes of lung tissues were observed by hematoxylin and eosin (H&E), Periodic acid Schiff (PAS) and Masson's trichrome staining. The purity of spicatoside A was 98.1% with a white powder (yield: 465.6mg). The treatment of spicatoside A in asthmatic mice significantly decreased the production of allergic mediator, OVA-specific IgE and Th2 cytokines, IL-4, IL-5 and IL-13 in sera and BALF. The numbers of inflammatory cells such as macrophages, lymphocytes, neutrophils and eosinophils in BALF of asthmatic mice were significantly reduced by the treatment of spicatoside A. Furthermore, the treatment of spicatoside A in asthmatic mice inhibited the structural damages of lung tissues with thickened bronchiolar epithelium and infiltration of inflammatory cells, the accumulation of mucus by the goblet cells hyperplasia and collagen in the bronchioles. These results suggest that spicatoside A of LT has a preventive effect on allergic asthma through the inhibition of lung inflammation and allergic response.

Effects of Rhizome Extract of Dioscorea batatas and Its Active Compound, Allantoin, on the Regulation of Myoblast Differentiation and Mitochondrial Biogenesis in C2C12 Myotubes.

With the aging process, a loss of skeletal muscle mass and dysfunction related to metabolic syndrome is observed in older people. Yams are commonly use in functional foods and medications with various effects. The present study was conducted to investigate the effects of rhizome extract of Dioscorea batatas (Dioscoreae Rhizoma, Chinese yam) and its bioactive compound, allantoin, on myoblast differentiation and mitochondrial biogenesis in skeletal muscle cells. Yams were extracted in water and allantoin was analyzed by high performance liquid chromatography (HPLC). The expression of myosin heavy chain (MyHC) and mitochondrial biogenesis-regulating factors, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), sirtuin-1 (Sirt-1), nuclear respiratory factor-1 (NRF-1) and transcription factor A, mitochondrial (TFAM), and the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) were determined in C2C12 myotubes by reverse transcriptase (RT)-polymerase chain reaction (RT-PCR) or western blot. The glucose levels and total ATP contents were measured by glucose consumption, glucose uptake and ATP assays, respectively. Treatment with yam extract (1 mg/mL) and allantoin (0.2 and 0.5 mM) significantly increased MyHC expression compared with non-treated myotubes. Yam extract and allantoin significantly increased the expression of PGC-1α, Sirt-1, NRF-1 and TFAM, as well as the phosphorylation of AMPK and ACC in C2C12 myotubes. Furthermore, yam extract and allantoin significantly increased glucose uptake levels and ATP contents. Finally, HPLC analysis revealed that the yam water extract contained 1.53% of allantoin. Yam extract and allantoin stimulated myoblast differentiation into myotubes and increased energy production through the upregulation of mitochondrial biogenesis regulators. These findings indicate that yam extract and allantoin can help to prevent skeletal muscle dysfunction through the stimulation of the energy metabolism.

Atractylenolide III Enhances Energy Metabolism by Increasing the SIRT-1 and PGC1α Expression with AMPK Phosphorylation in C2C12 Mouse Skeletal Muscle Cells.

Targeting energy expenditure provides a potential alternative strategy for achieving energy balance to combat obesity and the development of type 2 diabetes mellitus (T2DM). In the present study, we investigated whether atractylenolide III (AIII) regulates energy metabolism in skeletal muscle cells. Differentiated C2C12 myotubes were treated with AIII (10, 20, or 50 µM) or metformin (2.5 mM) for indicated times. The levels of glucose uptake, the expressions of key mitochondrial biogenesis-related factors and their target genes were measured in C2C12 myotubes. AIII significantly increased the glucose uptake levels, and significantly increased the expressions of peroxisome proliferator-activated receptor coactivator-1α (PGC1α) and mitochondrial biogenesis-related markers, such as, nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TFAM) and mitochondrial mass and total ATP contents. In addition, AIII significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of sirtuin1 (SIRT1). These results suggest that AIII may have beneficial effects on obesity and T2DM by improving energy metabolism in skeletal muscle.

MOK, a pharmacopuncture medicine, regulates thyroid dysfunction in L-thyroxin-induced hyperthyroidism in rats through the regulation of oxidation and the TRPV1 ion channel.

BACKGROUND: In this study, we evaluated the therapeutic effect of MOK, a pharmacopuncture medicine, on thyroid dysfunction in L-thyroxin (LT4)-induced hyperthyroidism rats. METHODS: The experimental hyperthyroidism model was prepared by the intraperitoneal injection of LT4 (0.5 mg/kg) once daily for 2 weeks in SD rats. MOK extract was injected at doses of 0.3 or 3 mg/kg on acupuncture points in the thyroid glands of LT4-induced hypothyroidism rats once a day for 2 weeks. The body temperature, body weight, and food/water intake were measured once a week for 2 weeks. The levels of thyroid hormones, total cholesterol, LDL-cholesterol, GOT, and GPT were measured in the sera of rats using ELISA and an automatic blood analyzer. The histological changes of thyroid tissues were observed by H&E staining. The expression of thermo-regulating protein, TRPV1 was determined by western blot in dorsal root ganglion (DRG) and brain tissues. We also measured the contents of GSH in the liver and antioxidant enzymes, SOD, and catalase in the liver, heart, and brain tissues by enzyme-based assay and Western blot, respectively. RESULTS: The acupuncture of MOK extract on the thyroid gland of LT4-induced hyperthyroidism rats significantly decreased the body temperature, and did not change body weight and food and water intakes. MOK acupuncture significantly increased the level of TSH, and decreased the levels of T3 and T4 in hyperthyroidism rats. The expression of TRPV1 was inhibited in both DRG and brain tissues after MOK acupuncture, and the levels of GOT, GPT, total cholesterol, and LDL-cholesterol were also decreased. MOK acupuncture also inhibited the pathological feature with follicular lining epithelial thicknesses and increased follicular colloid depositions in the thyroid glands of hypothyroidism. MOK acupuncture significantly increased hepatic GSH levels and decreased the expression of SOD and catalase in the liver, heart, and brain tissues of hyperthyroidism rats. CONCLUSIONS: These results suggest that the pharmacopuncture with MOK extract in hyperthyroidism can improve the pathophysiological changes through regulating the body temperature, thyroid hormones imbalance, lipid accumulation, and oxidation. This anti-hyperthyroidism effect of MOK pharmacopuncture is thought to be related to the control of thermo-regulating protein TRPV1 in DRG and brain.

Anti-Inflammatory Effects of Ginsenoside-Rh2 Inhibits LPS-Induced Activation of Microglia and Overproduction of Inflammatory Mediators Via Modulation of TGF-ß1/Smad Pathway.

Microglia activation plays an important role in neuroinflammation and contributes to several neurological disorders. Hence, inhibition of both microglia activation and pro-inflammatory cytokines may lead to the effective treatment of neurodegenerative diseases. In this study, we found that GRh2 inhibited the inflammatory response to lipopolysaccharide (LPS) and prevented the LPS-induced neurotoxicity in microglia cells. GRh2 significantly decreased the generation of nitric oxide production, and tumor necrosis factor-α, interleukin (IL)-6, IL-1ß, cyclooxygenase-2 and inducible nitric oxide synthase in LPS-induced activated microglia cells. Furthermore, GRh2 (20 and 50 µM) significantly increased TGF-ß1 expression and reduced the expression of Smad. These results suggest that GRh2 effectively inhibits microglia activation and production of pro-inflammatory cytokines via modulating the TGF-ß1/Smad pathway.

Neuroprotective effect of the hairy root extract of Angelica gigas NAKAI on transient focal cerebral ischemia in rats through the regulation of angiogenesis.

BACKGROUND: In this study, we investigated the neuroprotective effect of the hairy root extract of Angelica gigas NAKAI (Angelica Gigantis Radix) on transient focal cerebral ischemia in rats through the regulation of angiogenesis molecules. METHODS: Male Sprague-Dawley rats were induced focal cerebral ischemia by a transient middle cerebral artery occlusion (tMCAO) for 90 min, and then orally administrated with the water extract of A. gigas hairy roots (AG). After 24 h reperfusion, infarction volume and the changes of BBB permeability were measured by TTC and Evans Blue (EB) staining. The neuronal cell damage and the activation of glial cells were assessed by immunohistochemistry in the ischemic brain. The expression of angiogenesis-induced proteins such as angiopoietin-1 (Ang-1), and vascular endothelial growth factor (VEGF), inflammatory protein such as intercellular adhesion molecule-1 (CAM-1), tight junction proteins such as ZO-1, and Occludin and the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT were determined in the ischemic brains by Western blot, respectively. RESULTS: The treatment of AG extract significantly decreased the volumes of brain infarction, and edema in MACO-induced ischemic rats. AG extract decreased the increase of BBB permeability, and neuronal death and inhibited the activation of astrocytes and microglia in ischemic brains. AG extract also significantly increased the expression of Ang-1, Tie-2, VEGF, ZO-1 and Occludin through activation of the PI3K/Akt pathway. AG extract significantly increased the expression of ICAM-1 in ischemic brains. CONCLUSIONS: Our results indicate that the hairy root of AG has a neuroprotective effect in ischemic stroke.

Determination of total phenolics, flavonoid contents and antioxidant activity of different mBHT fractions: A polyherbal medicine.

In this study, antioxidant activity, total phenolic and flavonoids content of four different fractions from the traditional Korean polyherbal medicine of Modified Bo-yang-Hwan-o-Tang (mBHT) was determined using spectrophotometric methods. Antioxidant activity of fractions was expressed as percentage of DPPH radicals inhibition and IC50 values (µg/ml). Values in percentage ranged from 48.35 to 77.43%. The reducing powers of all the extracts were comparable with that of positive control sample of Butylated hydroxyl tolune (BHT) and ascorbic acid which was found to be dose dependent. Total phenolic content ranged from 106.83 ± 0.002 to 188.661 ± 0.002 mg/g, expressed as gallic acid equivalents. The total flavonoid contents varied from 28.44 ± 0.001 to 105.25 ± 0.001 mg/g, expressed as quarcetin equivalents. Ethyl acetate fractions of mBHT showed the highest phenolic (188.66 mg GAE/g) and flavonoids (105.25 mg QAE/g) contents and strong antioxidant activity. Total phenolics and flavonoid content of all the mBHT fractions were found reasonably correlated with IC50 of DPPH (R²=0.980 and 0.932, respectively). The high contents of phenolic compounds indicated that these compounds responsible for antioxidant activity. Therefore, ethyl acetate fractions of mBHT can be regarded as promising candidates for natural plant sources of antioxidants.

Effect of Kuwanon G isolated from the root bark of Morus alba on ovalbumin-induced allergic response in a mouse model of asthma.

The root bark of Morus alba L. (Mori Cortex Radicis; MCR) is traditionally used in Korean medicine for upper respiratory diseases. In this study, we investigated the antiasthmatic effect of kuwanon G isolated from MCR on ovalbumin (OVA)-induced allergic asthma in mice. Kuwanon G (1 and 10 mg/kg) was administered orally in mice once a day for 7 days during OVA airway challenge. We measured the levels of OVA-specific IgE and Th2 cytokines (IL-4, IL-5, and IL-13) in the sera or bronchoalveolar lavage (BAL) fluids and also counted the immune cells in BAL fluids. Histopathological changes in the lung tissues were analyzed. Kuwanon G significantly decreased the levels of OVA-specific IgE and IL-4, IL-5, and IL-13 in the sera and BAL fluids of asthma mice. Kuwanon G reduced the numbers of inflammatory cells in the BAL fluids of asthma mice. Furthermore, the pathological feature of lungs including infiltration of inflammatory cells, thickened epithelium of bronchioles, mucus, and collagen accumulation was inhibited by kuwanon G. These results indicate that kuwanon G prevents the pathological progression of allergic asthma through the inhibition of lung destruction by inflammation and immune stimulation.

Clean-DM1, a Korean Polyherbal Formula, Improves High Fat Diet-Induced Diabetic Symptoms in Mice by Regulating IRS/PI3K/AKT and AMPK Expressions in Pancreas and Liver Tissues.

OBJECTIVE: To investigate the effects of Clean-DM1 (C-DM1), a polyherbal formulation of Radix Scrophulariae, Radix Astragali, Rhizoma Atractylodis, and Radix Salviae Miltiorrhizae, on high-fat diet (HFD)-induced diabetes mice. METHODS: The information about active components of C-DM1 extract and molecular mechanism was obtained from network pharmacology analysis. Main compounds of C-DM1 extract by high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis were conducted for quality control. For in vivo study, mice were induced diabetes by HFD for 12 weeks. The mice in the normal group (Nor) were maintained with a regular diet and treated with saline by gavage. The HFD model mice were randomly divided into 3 groups, including a HFD diabetic model group, a C-DM1 extract-administered group (C-DM1, 500 mg/kg), and metformin-administered groups (Met, 500 mg/kg), 8 mice in each group. Food intake, body weight (BW), and fasting blood glucose (FBG) levels were recorded weekly for 4 weeks. After 4 weeks of treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood glucose, low-density lipoprotein cholesterol (LDL-C) were determined using an automated clinical chemistry analyzer, and homeostatic model for assessing insulin resistance (HOMA-IR) levels and oral glucose tolerance test (OGTT) were detected. The histopathological changes of liver and pancreatic tissues were observed by hematoxylin-eosin staining. Insulin receptor substrate (IRS)/phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (AKT) and adenosine 5'-monophosphate-activated protein kinase (AMPK) expressions in liver and pancreas tissues were detected by Western blot analysis. RESULTS: HPLC-MS identified dihydroisotanshinone, dihydroisotanshinone I, cryptotanshinone, harpagoside, and atractyloside A in C-DM1 extract. The administration of C-DM1 extract significantly decreased body weight, calorie intake, and the levels of blood glucose and insulin in the diabetic mice (P<0.05 or P<0.01). The C-DM1 extract administration improved the impaired glucose tolerance and insulin resistance in the diabetic mice and significantly decreased the levels of LDL-C, ALT and AST (P<0.01). The C-DM1 extract inhibited the histopathological changes of fatty liver and hyperplasia of pancreatic islets in the diabetic mice. The C-DM1 extract significantly increased the phosphorylation of IRS, AKT, and AMPK and the expression of PI3K in pancreas and liver tissues (P<0.05 or P<0.01), which was consistent with the analysis results of network pharmacology. CONCLUSION: C-DM1 extract improved diabetes symptoms in long-term HFD-induced mice by regulation of IRS/PI3K/AKT and AMPK expressions in pancreas and liver tissues, suggesting that C-DM1 formulation may help prevent the progression of T2DM.

Anti-inflammatory effects of prosapogenin III from the dried roots of Liriope platyphylla in LPS-stimulated RAW264.7 cells.

Liriope platyphylla has been reported to possess various biological activities, including anti-asthma, anti-inflammation, anti-diabetes, and neuriotogenic properties. In this study, we evaluated the effects of prosapogenin III isolated from the roots of L. platyphylla (Liriopis Tuber) on inflammatory responses in lipopolysaccharide (LPS) stimulated RAW264.7 mouse macrophages. We investigated LPS-induced production/expression of inflammatory mediators such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxigenase-2 (COX-2), and proinflammatory cytokines, including interleukin-1ß (IL-1ß) and interleukin (IL)-6 in RAW264.7 cells. We also performed Western blot analysis for determination of the phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK) 1/2, p38, and c-Jun N-terminal kinase (JNK), and nuclear translocation of nuclear factor-κB (NF-κB) in LPS-stimulated cells. Treatment with prosapogenin III resulted in significant inhibition of NO production in LPS-stimulated Raw264.7 cells through suppression of iNOS expression. Treatment with prosapogenin III resulted in a significant decrease in expressions of COX-2, IL-1ß, and IL-6 through down-regulation of their mRNA or protein in LPS-stimulated cells. In addition, treatment with prosapogenin III resulted in potently inhibited phosphorylation of three MAPKs, including ERK1/2, p38, and JNK in LPS-stimulated cells. Treatment with prosapogenin III also resulted in suppression of the nuclear translocation of NF-κB in LPS-stimulated cells. These results indicate that prosapogenin III of Liriopis Tuber has anti-inflammatory effects in activated macrophages through inhibition of production of inflammatory mediators by blockade of the MAPK/NF-κB pathway.

The extract of Cinnamomum cassia twigs inhibits adipocyte differentiation via activation of the insulin signaling pathway in 3T3-L1 preadipocytes.

CONTEXT: Obesity is associated with a number of diseases with metabolic abnormalities such as type 2 diabetes (T2D). Medicinal plants have been widely used for the treatment of obesity and related complications. OBJECTIVE: In this study, we investigated the antidiabetic properties of the extract of twigs of Cinnamomum cassia Blume (Lauraceae) (Cinnamomi Ramulus; CR) in 3T3-L1 murine preadipocytes. MATERIALS AND METHODS: 3T3-L1 cells were differentiated into adipocytes for 3 d in insulin-conditioned medium and then treated with CR extract at concentrations of 100 and 500 µg/mL for 6 d. Adipocyte differentiation was measured by Oil Red O staining, and the expression of master transcription factors, peroxisome proliferator-activated receptor-gamma (PPARγ), CCAAT/enhancer binding protein-alpha (C/EBPα), and sterol regulatory element binding protein-1c (SREBP-1c), and lipid metabolism factors were investigated by reverse transcription-polymerase chain reaction (RT-PCR). The activation of the AMP-activated protein kinase (AMPK)/insulin signaling pathway was assessed by western blot analysis. RESULTS: CR extract significantly reduced lipid accumulation and down-regulated the expression of PPARγ, C/EBPα, and SREBP-1c in 3T3-L1 adipocytes. CR extract also suppressed the expression of fatty acid synthase (FAS), acyl-CoA synthase, and perilipin. Moreover, CR extract markedly up-regulated the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC). In addition, CR extract effectively increased the expression levels of glucose transporter-4 (GLUT-4), phosphatidylinositol 3-kinase (PI3K), and insulin receptor substrate-1 (IRS-1) in 3T3-L1 adipocytes. DISCUSSION AND CONCLUSION: These results suggest that CR extract may have therapeutic potential as a natural agent for the improvement of T2D via regulation of the insulin-dependent signaling pathway.

The roots of Atractylodes japonica Koidzumi promote adipogenic differentiation via activation of the insulin signaling pathway in 3T3-L1 cells.

BACKGROUND: Type 2 diabetes (T2D) is a complex metabolic disorder characterized by insulin resistance and hyperglycemia. Peroxisome proliferator-activated receptor gamma (PPARγ) is a key transcription factor and plays an important role in the regulation of genes involved in adipogenic differentiation, glucose metabolism and insulin signal transduction. METHODS: In this study, the effects of the root extract of Atractylodes japonica Koidzumi (Atractylodis Rhizoma Alba, ARA) on the differentiation of 3T3-L1 preadipocytes and the possible mechanism of glucose transport were investigated. 3T3-L1 cells were cultured with insulin and ARA extract. RESULTS: In 3T3-L1 cells, ARA extract significantly enhanced adipogenic differentiation and upregulated the expression of PPARγ genes and protein in a dose-dependent manner. ARA also promoted glucose transport by increasing the glucose transporter 4 (GLUT-4), phosphatidylinositol 3-kinase (PI3K) and insulin receptor substrates-1 (IRS-1) levels. CONCLUSION: Our results suggest that ARA extract may be an attractive therapeutic agent for managing T2D via promoting the differentiation of adipocytes with the upregulation of PPARγ levels and the activation of the insulin signaling pathway.

Cryptotanshinone from Salviae miltiorrhizae radix inhibits sodium-nitroprusside-induced apoptosis in neuro-2a cells.

The root of Salvia miltiorrhiza (Salviae miltiorrhizae radix), a herbal medicine has widely been used for the treatment of pain, miscarriage and oedema. In this study, we evaluated the neuroprotective effect of cryptotanshinone (CRT) from Salviae miltiorrhizae radix on sodium-nitroprusside (SNP)-induced apoptosis in neuro-2a (N2a) cells, and further investigated its action mechanism in signalling pathways. The effects of CRT against SNP-induced toxicity, mitochondrial membrane potential (MMP) changes, and oxidants/antioxidant defences and apoptotic signalling pathways were investigated in N2a cells. Cryptotanshinone significantly inhibited SNP-induced cell toxicity and the generation of reactive oxygen and nitrogen species (RONS), and improved MMP in N2a cells. Cryptotanshinone significantly suppressed SNP-induced peroxidation of lipid and protein, and the expression of Gclc mRNA. In the signalling pathway, CRT effectively blocked SNP-induced activation of NF-κB and ERK1/2 and JNK MAPK pathways through the elevation of Akt and cyclic AMP response element binding protein. Furthermore, CRT remarkably reduced the increase of mitochondrial Bax/Bcl-2 ratio, the release of cytochrome c from mitochondria to cytosol, and the activations of cytosolic procaspase-3 and nuclear inactive poly ADP (adenosine diphosphate)-ribose polymerase by SNP-induced apoptosis. These results indicate that CRT has neuroprotective effects against SNP-induced apoptosis in neuronal cells via the regulation of mitochondrial apoptotic cascades and antiapoptotic cellular signalling pathways.

Synthesis and antiproliferative activity of novel α-aminophosphonates.

A novel series of carbazole-based α-aminophosphonates were synthesized by three component coupling of 6-bromo-9-ethyl-9H-carbazole-3-carbaldehyde, amine and diethyl phosphite using polyethylene glycol (PEG-400) as a green reaction media. The antiproliferative activity of these molecules was evaluated against three cancer cell lines. Of these, compounds 4c, 4e and 4m were found to exhibit good antiproliferative activity against three cancer cells, A549, MCF-7, and NCI-N87.

Monotropein Improves Dexamethasone-Induced Muscle Atrophy via the AKT/mTOR/FOXO3a Signaling Pathways.

The present study aimed to investigate the effects of monotropein (MON) on improving dexamethasone (DEX)-induced muscle atrophy in mice and C2C12 mouse skeletal muscle cells. The body weights, grip strengths, and muscle weights of mice were assessed. The histological change in the gastrocnemius tissues was also observed through H&E staining. The expression of myosin heavy chain (MyHC), muscle ring finger 1 (MuRF1), and muscle atrophy F-box (Atrogin1) and the phosphorylation of AKT, mTOR, and FOXO3a in the muscle tissues of mice and C2C12 myotubes were analyzed using Western blotting. MON improved muscle atrophy in mice and C2C12 myotubes by regulating catabolic states via the AKT/mTOR/FOXO3a signaling pathways, and enhanced muscle function by the increases of muscle mass and strength in mice. This suggests that MON could be used for the prevention and treatment of muscle atrophy in patients.

Effects of Jowiseungki-tang on high fat diet-induced obesity in mice and functional analysis on network pharmacology and metabolomics analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese and Korean medicine, Jowiseungki-tang (JST) is a prescription for diabetes mellitus (DM) treatment. However, little scientific evidence is known of its effect in diabetic condition. AIMS: We assessed the effects of JST on high-fat diet (HFD)-induced obesity with inflammatory condition in mice and to analyze the therapeutic function of JST on network pharmacology as well as targeted metabolomics. MATERIALS AND METHODS: JST administration at 100 mg/kg and 500 mg/kg for a period of 4 weeks in HFD-induced obese mice, body weight gain, energy utility, calorie intake, and levels of glucose, insulin, total cholesterol, triglyceride, LDL-cholesterol as well as interleukin-6 were measured. Measurements of HDL-cholesterol (HDL-C) were performed and compared to those of the control group. Moreover, the therapeutic function of JST on obesity was analyzed furtherly based on network pharmacology and targeted metabolomics methods. RESULTS: Administration of JST at 100 mg/kg and 500 mg/kg for a period of 4 weeks in HFD-induced obesity mice significantly decreased the body weight gain, energy utility, calorie intake, and levels of insulin, total cholesterol, LDL-cholesterol, triglyceride, and interleukin-6. However, HDL-cholesterol (HDL-C) levels showed marked elevation relative to control groups. JST administration strongly inhibited expressions of inducible nitric oxide synthase, inflammatory proteins, and cyclooxygenase-2 in the pancreas, stomach, and liver tissues, and reduced hepatic steatosis and pancreatic hyperplasia. In network pharmacological analysis, the putative functional targets of JST are underlie on modulation of cofactor-, coenzyme-, and fatty acid-bonding, insulin resistance, and inflammatory response, fine-tuned the phosphatase binding and signal pathway activation, such as mitogen activated protein kinases, phosphatidylinositol 3-kinases/protein kinase B, protein kinase C, and receptor of glycation end products as well-advanced glycation end products. According to the metabolomics analysis, the contents and energy metabolites, and medium and long chain fatty acids was significantly changed in mice pancreases. CONCLUSIONS: JST is a valuable prescription for treatment of patients with DM in traditional clinics through inhibition of obesity, inflammatory condition and metabolism.

Antiallergic effect of Ostericum koreanum root extract on ovalbumin-induced allergic rhinitis mouse model and mast cells.

OBJECTIVE: In the present study, the anti-allergic effect of OR extract was evaluated on an ovalbumin (OVA)-induced allergic rhinitis in mice and rat peritoneal mast cells (RPMC). METHODS: Balb/c mice were systemically sensitized to OVA followed by intraperitoneal and nasal allergen challenges. We investigated the effect of OR extract on allergic symptoms, serological marker production and histological changes of the nasal mucosa in a mouse model of allergic rhinitis. We observed mast cell degranulation and detected the production of histamine and inflammatory cytokines by ELISA. RESULTS: Compared to the OVA-control group, oral administration of OR extract at doses of 50 and 100 mg/kg significantly (p < 0.001) decreased the serum levels of histamine, OVA-specific IgE and Th2 cytokine,IIL-4 as well as increasing Th1 cytokine, IFN-gamma. Oral administration of OR extract also attenuated disease progression as determined by nasal symptoms and histological changes of the nasal mucosa in OVA-sensitized mice. Furthermore, treatment with OR extract at doses of 0.2, 0.5 ad 1 mg/mL in RPMC significantly (p <0.01, p <0.001 and p <0.001, respectively) decreased compound 48/80-induced histamine release and suppressed mast cell degranulation. Treatment with OR extract in RPMC also inhibited PMA/A23187-induced production of inflammatory cytokines such as TNF-alpha and IL-6. The mechanism of action underlying OR extract in allergic inflammation appears to be inhibition of the phosphorylation of ERK1/2 and p38 MAPK, in addition to blocking of the NFKB pathway. CONCLUSIONS: These results indicate that OR extract has the potential to be a source of antiallergic agents for use in allergen and/or mast cell-mediated diseases including allergic rhinitis.

Effects of Root Extract of Morinda officinalis in Mice with High-Fat-Diet/Streptozotocin-Induced Diabetes and C2C12 Myoblast Differentiation.

Type 2 diabetes is the most common type of diabetes and causes a decline in muscle quality. In this study, we investigated the effects of the root extract of Morinda officinalis (MORE) on skeletal muscle damage in mice with high-fat-diet (HFD)/streptozotocin (STZ)-induced diabetes and the expression of myogenic and biogenesis regulatory proteins in C2C12 myoblast differentiation. An in vivo model comprised C57BL/6N mice fed HFD for 8 weeks, followed by a single injection of STZ at 120 mg/kg. MORE was administered at 100 and 200 mg/kg once daily (p.o.) for 4 weeks. The changes in body weight, calorie intake, and serum levels of glucose, insulin, total cholesterol (TCHO), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), aspartate transaminase (AST), and alanine aminotransferase (ALT) were investigated in diabetic mice. The histological changes in the gastrocnemius muscle were observed by H&E staining, and then the myofiber size was measured. The expression of the myogenic (MHC, myogenin, and MyoD) and biogenesis (PGC-1α, SIRT1, NRF1, and TFAM) regulatory proteins was examined in the muscle tissues and differentiated C2C12 myoblasts by Western blot, respectively. The administration of MORE at 200 mg/kg in mice with HFD/STZ-induced diabetes significantly reduced weight gains, calorie intake, insulin resistance, and serum levels of glucose, TCHO, LDL-C, AST, and ALT. MORE administration at 100 and 200 mg/kg significantly increased serum insulin and HDL-C levels in diabetic mice. In addition, MORE significantly increased the expression of MHC, myogenin, MyoD, PGC-1α, SIRT1, NRF1, and TFAM in muscle tissues as well as increased the myofiber size in diabetic mice. In C2C12 myoblast differentiation, MORE treatment at 0.5, 1, and 2 mg/mL significantly increased the expression of myogenic and biogenesis regulatory proteins in a dose-dependent manner. MORE improves diabetes symptoms in mice with HFD/STZ-induced diabetes by improving muscle function. This suggests that MORE could be used to prevent or treat diabetes along with muscle disorders.

Preventive role of PD-1 on MPTP-induced dopamine depletion in mice.

Many current studies of Parkinson's disease (PD) suggest that inflammation is involved in the neurodegenerative process. PD-1, a traditional Korean medicine, used to treat various brain diseases in Korea. This study was designed to investigate the effect of PD-1 extract in the Parkinson's model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioned mice. The MPTP administration caused the dopamine neuron loss in the striatum and substantia nigra pars compacta (SNpc), which was demonstrated by a depletion of tyrosine hydroxylase (TH). In addition, a reduction of bcl-2 expression with elevation of bax expression, caspase-3 activation, and release of cytochrome c into cytosol in dopaminergic neurons of SNpc were noted. Oral administration of PD-1 extract (50 and 100 mg kg(-1)) attenuated the MPTP-induced depletion of TH proteins in the striatum and SNpc and prevented the apoptotic effects. These results indicate that PD-1 extract is able to protect dopaminergic neurons from MPTP-induced neuronal death, with important implications for the treatment of PD.