Efficacy of Veronica incana for Treating Osteoarthritis Induced by Monosodium Iodoacetate in Rats.

The aim of this study is to investigate the efficacy and the underlying mechanism of Veronica incana in osteoarthritis (OA) induced by intraarticular injection of monosodium iodoacetate (MIA). The selected major four compounds (A-D) of V. incana were found from fractions 3 and 4. Its structure elucidation was determined by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) data analysis and nuclear magnetic resonance (NMR) data comparison with literature. MIA (50 µL with 80 mg/mL) for the animal experiment was injected into the right knee joint. The V. incana was administered orally every day to rats for 14 days from 7 days after MIA treatment. Finally, we confirmed the four compounds: (A) verproside; (B) catalposide; (C) 6-vanilloylcatapol; and (D) 6-isovanilloylcatapol. When we evaluated the effect of V. incana on the MIA injection-induced knee OA model, there were a noticeable initial decreased in hind paw weight-bearing distribution compared to the Normal group (P < .001), but V. incana supplementation resulted in a significant increase in the weight-bearing distribution to the treated knee (P < .001). Moreover, the V. incana treatment led to a decrease in the levels of liver function enzymes and tissue malondialdehyde (P < .05 and .01). The V. incana significantly suppressed the inflammatory factors through the nuclear factor-kappa B signaling pathway and downregulated the expression of matrix metalloproteinases, which are involved in the degradation of the extracellular matrix (P < .01 and .001). In addition, we confirmed the alleviation of cartilage degeneration through tissue stains. In conclusion, this study confirmed the major four compounds of V. incana and suggested that V. incana could serve as an anti-inflammatory candidate agent for patients with OA.

The Synergistic Action of Metformin and Glycyrrhiza uralensis Fischer Extract Alleviates Metabolic Disorders in Mice with Diet-Induced Obesity.

Metformin, an antidiabetic drug, and Glycyrrhiza uralensis Fischer (GU), an oriental medicinal herb, have been reported to exert anti-obesity effects. This study investigated the synergistic action of metformin and GU in improving diet-induced obesity. Mice were fed a normal diet, a high-fat diet (HFD), or HFD + 0.015% GU water extract for 8 weeks. The HFD and GU groups were then randomly divided into two groups and fed the following diets for the next 8 weeks: HFD with 50 mg/kg metformin (HFDM) and GU with 50 mg/kg metformin (GUM). GUM prevented hepatic steatosis and adiposity by suppressing expression of mRNAs and enzyme activities related to lipogenesis in the liver and upregulating the expression of adipocyte mRNAs associated with fatty acid oxidation and lipolysis, and as a result, improved dyslipidemia. Moreover, GUM improved glucose homeostasis by inducing glucose uptake in tissues and upregulating mRNA expressions associated with glycolysis in the liver and muscle through AMP-activated protein kinase activation. GUM also improved inflammation by increasing antioxidant activity in the liver and erythrocytes and decreasing inflammatory cytokine productions. Here, we demonstrate that GU and metformin exert synergistic action in the prevention of obesity and its complications.

Artemisiae argyi Water Extract Alleviates Obesity-Induced Metabolic Disorder.

Artemisiae argyi is a well-known traditional herbal medicine used in East Asia. Although the antibacterial and anti-inflammatory effects of A. argyi have been reported, its efficacy in improving obesity has not been yet evaluated. In this study, mice were fed a normal diet (AIN-93), a high-fat diet (HFD, 60% of kcal from fat), and an HFD with 0.1% of A. argyi water extract for 16 weeks. The body weight and body fat in A. argyi-fed mice significantly decreased via upregulation of the mRNA expression of fatty acid oxidation-related genes, with a simultaneous decrease in plasma lipid content and leptin levels. A. argyi water extract also ameliorated hepatic steatosis by restricting lipogenesis via lowering the activities of fatty acid synthase and phosphatidic acid phosphatase. Consistently, hepatic histological analysis indicated that A. argyi water extract decreased hepatic lipid accumulation in accordance with the hepatic H, E and Oil Red O-stained area. Additionally, A. argyi ameliorated the impaired glucose homeostasis by increasing the mRNA expression of AMP-activated kinase and glycolysis-related genes. In conclusion, our results indicate that A. argyi can be used to treat obesity-related metabolic conditions.

Boswellia serrata Extract, 5-Loxin®, Prevents Joint Pain and Cartilage Degeneration in a Rat Model of Osteoarthritis through Inhibition of Inflammatory Responses and Restoration of Matrix Homeostasis.

Osteoarthritis (OA) is a chronic, progressive joint disease associated with pain, functional impairment, and diminished quality of life in affected individuals. At a societal level, it also has a high economic burden. Boswellia serrata has been reported to have potent anti-inflammatory, antiarthritic, and analgesic effects. The aim of this study was to explore the therapeutic potential and possible underlying mechanism of 5-Loxin®, a standardized Boswellia serrata extract, in a rat model of OA. The OA model was established by the intra-articular injection of 50 µL of monosodium iodoacetate (MIA) (60 mg/mL). 5-Loxin® was administered orally, and efficacy was evaluated through serum analysis, real-time polymerase chain reaction (PCR), histologic staining, and micro-computed tomography (micro-CT). Results indicated that administration of 5-Loxin® can relieve OA joint pain through inhibition of both inflammatory processes and cartilage degeneration. In the group of rats treated with 5-Loxin®, the suppression of inflammatory enzymes such as cyclooxygenase (COX)-2 and 5-lipoxygenase (LOX) resulted in a significant reduction in the prostaglandin (PG) E2 and leukotriene (LT) B4 levels. Moreover, 5-Loxin® ameliorated the deterioration of the main components of the articular extracellular matrix (ECM), such as glycosaminoglycans (GAGs) and aggrecan, through the downregulation of matrix metalloproteinases (MMPs). These findings suggest that 5-Loxin® may be a potential therapeutic agent for the treatment of OA.

Gardeniae Fructus Extract Alleviates Dexamethasone-Induced Muscle Atrophy in Mice.

Muscle atrophy (MA) is a case in which protein degeneration occurs excessively due to an imbalance between protein synthesis and breakdown, and is characterized by decreased muscle mass and weakened muscle strength. Despite mounting concern about MA, the number of patients with MA is increasing every year. The aim of the present study was to assess the impact of Gardeniae Fructus (GF) hot water extract on dexamethasone (DEX)-induced MA in mice. C57BL/6N mice were grouped (n = 8) as follows: Normal mice (Normal), MA mice were treated with distilled water (Control), MA mice were treated with GF 100 mg/kg (GF100), MA mice were treated with GF 200 mg/kg (GF200). For 10 days, DEX (25 mg/kg body weight, i.p.) injection was used to induce MA, and GF was administered. GF treatment restored the muscle weight decreased due to MA, and in particular, the weights of EDL+TA and Sol were significantly increased in the GF200 group. Also, it was confirmed that the swimming time was improved in the GF200 group. In addition, the expression of NADPH oxidase related to oxidative stress was significantly reduced, and protective (insulin-like growth factor I/phosphoinositide 3-kinase/protein kinase B pathway) and catabolic (AMP-activated kinase [AMPK]/sirtuin 1 [SIRT1]/proliferator-activated receptor-gamma coactivator-1α (PGC-1α)-forkhead box O (FOXO) pathway) pathways were significantly modulated. These results demonstrate that GF regulates muscle protein synthesis and catabolic pathways, and in particular, it is judged to improve MA by regulating the proteolytic AMPK/SIRT1/PGC-1α-FOXO pathway.

Citrus unshiu Peel Attenuates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice due to Modulation of the PI3K/Akt Signaling Pathway and MAPK and NF-κB.

Aim: Citrus unshiu peel has been used to treat various diseases in traditional East Asian medicine including Korea, and many studies have been reported regarding inflammatory diseases including ulcerative colitis (UC). However, the underlying mechanism by which Citrus unshiu peel modulates inflammation in UC remains unclear. Therefore, this study aimed to evaluate the therapeutic effect and underlying mechanism of Citrus unshiu peel water extract (CUP) for UC. Methods: The experiment for UC was conducted with 8-week-old male Balb/c mice. After 1 week of adaptation, acute colitis was induced in all groups except the normal group by 5% DSS dissolved in drinking water for 1 week. Balb/c mice were divided into 5 groups (n = 8/group): control group (Control), distilled water-treated group (DSS), 100 mg/kg sulfasalazine-treated group (SASP), 100 mg/kg CUP-treated group (CUPL), and 200 mg/kg CUP-treated group (CUPH). The efficacy of CUP on UC was evaluated by biochemical analyses such as ROS and MPO in serum and MDA in tissues, and expression of proteins related to inflammation and apoptosis was evaluated through Western blot. Results: As a result of confirming the macroscopic changes and H&E staining in colon tissues to confirm the preventive and therapeutic effects of CU, decrease in colon length and inflammatory lesions were inhibited in the CUP-treated group compared to the DSS group. In addition, as a result of serum ROS and tissue MDA analysis and oxidative stress-related protein analysis, it was significantly decreased in the CUP-administered group compared to the control group. In addition, treatment with CUP not only inactivated MAPK, p-IκBα, and NF-κBp65 by blocking the PI3K/Akt pathway but also significantly reduced the expression of inflammatory cytokines. Conclusion: These results show that CUP not only suppresses oxidative stress in UC but also regulates inflammation-related proteins and apoptotic proteins by regulating the PI3K/Akt signaling pathway, suggesting that it has the potential as a material for developing new natural therapeutic agents for UC.

The Potential Hepatoprotective Effect of Paeoniae Radix Alba in Thioacetamide-Induced Acute Liver Injury in Rats.

AIM: Acute liver injury (ALI) can occur for various reasons by induced inflammation and apoptosis of liver cells including hepatocytes, Kupffer cells, and hepatic stellate cells. Thioacetamide (TAA), which is a classic hepatotoxin, causes oxidative stress, membrane damage, and accumulation of lipid droplets and subsequently provokes consecutive liver injury. In the current study, we tested whether Paeoniae Radix Alba (PR) could alleviate TAA-induced ALI. METHODS: Thirty-five male rats were equally separated into five groups. The first group was the normal group, which received distilled water only. The remaining four groups received intraperitoneal TAA (200 mg/kg) for 3 days to induce ALI. The four groups were divided into the control group (no treatment), silymarin-treated, 100 mg/kg PR-treated, and 200 mg/kg PR-treated. The efficacy of PR against hepatotoxicity was evaluated in terms of the serum biochemical index and protein expression associated with inflammation and apoptosis. Moreover, the dissected livers were analyzed by hematoxylin and eosin stain. RESULTS: PR alleviated liver dysfunction as evidenced by decreased levels of aspartate aminotransferase, alanine aminotransferase, and ammonia. Phosphorylated AMP-activated protein kinase (AMPK) and Sirtuin 1 (Sirt1) levels were obviously decreased in the TAA control group, whereas PR reversed these changes. PR also prevented deteriorative effects through inhibition of inflammation and apoptosis via nuclear transcription factor-kappa Bp65 (NF-κBp65) inactivation. Moreover, we found that the hepatoprotective effect of PR pretreatment was mediated by restoration of histopathological changes. CONCLUSION: PR efficiently blocked both the inflammatory response and apoptosis through activating the AMPK/Sirt1/NF-κBp65 pathway. Therefore, PR is considered a potential therapeutic agent against ALI.

Scutellariae Radix and Citri Reticulatae Pericarpium Mixture Regulate PPARγ/RXR Signaling in Reflux Esophagitis.

OBJECTIVE: Gastroesophageal reflux disease (GERD) is a gastrointestinal disorder in which stomach contents reflux into the esophagus, causing complications such as mucosal damage. GERD is a very common disease and is on the rise worldwide. The aim of this study was to assess the impact of a Scutellariae Radix and Citri Reticulatae Pericarpium mixture (SC) on esophageal mucosal injury in rats with chronic acid reflux esophagitis (CARE). METHODS: After inducing reflux esophagitis through surgery, the group was separated and the drug was administered for 2 weeks: normal rats (Normal, n = 8), CARE-induced rats were treated with distilled water (Control, n = 8), CARE-induced rats were treated with vitamin E 30 mg/kg body weight (VitE, n = 8), CARE-induced rats were treated with SC 100 mg/kg body weight (SC100, n = 8), and CARE-induced rats were treated with SC 200 mg/kg body weight (SC200, n = 8). RESULTS: SC treatment significantly reduced the degree of esophageal mucosal damage, significantly reduced levels of MDA and MPO, and inhibited the activation of the NF-κB inflammatory pathway by activating the PPARγ/RXR pathway. In addition, SC treatment significantly regulated the expression of arachidonic acid-related proteins (COX-1, COX-2, and PGE2) and modulated the MMP/TIMP proteins in reflux esophagitis. CONCLUSION: Consequently, SC improved the damage to the esophageal mucosa. Also, the anti-inflammatory effects of the SC suggested the inhibition of NF-κB pathway through the activation of the PPARγ/RXR pathway, thereby reducing the expression of inflammation-related cytokines.

Immunomodulatory and anti-inflammatory effects of Phellinus linteus mycelium.

BACKGROUND: The present study extensively aimed to evaluate the underlying mechanism of the immunomodulatory and anti-inflammatory effects of Phellinus linteus mycelium (PLM). METHODS: To assess whether PLM influences the production of markers related to inflammation, Lipopolysaccharide (LPS)-stimulated RAW264.7 cells were treated with PLM (50, 100, 200, and 500 µg/mL). Splenocyte, thymus, peritoneal exudate cells (PEC), and peripheral blood mononuclear cells (PBMC) were isolated from the Balb/c mice treated with Korean red ginseng or PLM once a day for 5 weeks. Moreover, all mice except normal mice were stimulated with 10% proteose peptone (PP) treated 3 days before the sacrifice and 2% starch treated 2 days before the sacrifice. Subsequently, the cytotropic substance was evaluated by using flow cytometry analysis and ELISA assay. RESULTS: PLM200 treatment significantly suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) and inhibited the release of proinflammatory cytokines such as interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α dose-dependently in the LPS-stimulated RAW264.7 cells. PLM200 supplementation showed a significant increase in IL-2, IL-12, and interferon (IFN)-γ production and upregulated the ratio of IFN-γ (T-helper type 1, Th1) to IL-4 (T-helper type 2, Th2) in splenocytes. After PLM200 treatment, the significant elevation of CD4+CD25+, CD4+&CD8+, and CD4+CD69+ treatment were detected in thymus. Moreover, CD4+ and CD4+CD69+ in PBMC and CD69+ in PEC were also shown in a significant increase. CONCLUSIONS: Taken together, these results showed an immunomodulatory effect of PLM about an elevated INF-γ/IL4 ratio, as an index of Th1/Th2, as well as the anti-inflammatory effect in the LPS-stimulated RAW264.7 cells. Therefore, our findings demonstrate that PLM possesses immunostimulatory and anti-inflammatory effects.

Beneficial Effect of Taraxacum coreanum Nakai via the Activation of LKB1-AMPK Signaling Pathway on Obesity.

OBJECTIVE: Liver kinase B (LKB) 1 and AMP-activated protein kinase (AMPK) are master regulators and sensors for energy homeostasis. AMPK is mainly activated via phosphorylation of LKB1 under energy stress. Here, we highlighted the antiobesity effect and underlying mechanism of Taraxacum coreanum Nakai (TCN) in connection with LKB1-AMPK signaling pathway. METHODS: Male C57BL/6 mice were fed on a high-fat diet (60% kcal fat; HFD) to induce obesity. Simultaneously, they received 100 or 200 mg/kg TCN orally for 5 weeks. We measured the body weight gain and liver weight along with liver histology. Moreover, the changes of factors related to lipid metabolism and ß-oxidation were analyzed in the liver, together with blood parameters. RESULTS: The body weights were decreased in mice of the TCN200 group more than those of the HFD control group. Moreover, TCN supplementation lowered serum triglyceride (TG) and total cholesterol (TC) levels, whereas TCN increased HDL-cholesterol level. Liver pathological damage induced by HFD was alleviated with TCN treatment and accompanied with significant reduction in serum AST and ALT activities. In addition, TCN significantly increased the expression of p-AMPK compared with the HFD control group via the activation of LKB1/AMPK signaling pathway. Lipid synthesis gene like ACC was downregulated and factors related to ß-oxidation such as carnitine palmitoyl transferase-1 (CPT-1) and uncoupling protein 2 (UCP-2) were upregulated through peroxisome proliferator-activated receptor (PPAR) α activation. CONCLUSION: Taken together, these data suggest that TCN treatment regulates lipid metabolism via LKB1-AMPK signaling pathway and promotes ß-oxidation by PPARα; hence, TCN may have potential remedy in the prevention and treatment of obesity.

Protective Effects of Inflammation of Curcumae Longae Rhizoma 30% EtOH Extract on Acute Reflux Esophagitis Rats.

Gastroesophageal reflux disease (GERD) is induced by the reflux of stomach contents or gastric acid, pepsin into the esophagus for prolonged periods of time due to defection of the lower esophageal sphincter. Reflux esophagitis is a disease found in less than 50% of GERD patients. This study is aimed at evaluating the protective effect of Curcumae longae Rhizoma 30% EtOH extract (CLR) in acute reflux esophagitis (ARE) rats. CLR measured antioxidant activity through in vitro experiments. Based on the results, we performed experiments in vivo. Before 90 min ARE induction, CLR was administered orally by concentration. ARE was derived by linking the metastatic junction between pylorus and forestomach and corpus in Sprague-Dawley rats. And rats were sacrificed 5 h after surgery. We analyzed the expression of antioxidant and inflammatory-related markers by western blot and observed the production of alanine aminotransferase (ALT), aspartate aminotransferase (AST), reactive oxygen species (ROS), peroxynitrite (ONOO-), and thiobarbituric acid reactive substance (TBARS). The administration of CLR reduced esophagus tissue damage in rats with acute reflux esophagitis and decreased the elevated ALT, AST, ROS, ONOO-, and TBARS. In addition, CLR effectively increased antioxidant-related factors and reduced inflammatory protein. Overall, these results suggest that CLR would be used as a therapeutic material in protection and treatment for ARE. Overall, CLR treatment informed that markedly ameliorated inactivation of NF-κB led to the inhibition of the expressions of proinflammatory proteins. These results suggest that CLR would be used as a therapeutic material in protection and treatment for ARE.

Anti-Melanogenic Effects of Korean Red Ginseng Oil in an Ultraviolet B-Induced Hairless Mouse Model.

A 'remedy for all' natural product widely known in the Korean Peninsula is called Panax Ginseng Meyer. Globalization represents a persistent risk to the ozone layer, leading to bountiful amounts of Ultra-Violet B beams (UVB). The variety in human skin hues is ascribed to the characteristic color called Melanin. However, Melanin overproduction due to UVB beams promotes skin staining and tumorigenesis, a process called photo aging, which damages skin quality. To assess the effects of Korean Red Ginseng Oil (KGO) on photo aging, the murine melanoma cell lines B16/F10 were used in vitro and HRM-2 hairless mice exposed to UVB were studied in vivo. Our results revealed that KGO reduced tyrosinase activity and melanin production in B16/F10 cells along with the suppression of upstream factors involved in the melanin production pathway, both transcriptionally and transitionally. In the in vivo studies, KGO suppressed the expression of Matrix Metalloproteinase (MMP) and Interleukins along with a reduction of depth in wrinkle formation and reduced collagen degradation. Moreover, the feed intake and feed efficiency ratio that decreased as a result of UVB exposure was also improved by KGO treatment. In light of our results, we conclude that KGO can have considerable benefits due to its various properties of natural skin enhancement.

New approach of medicinal herbs and sulfasalazine mixture on ulcerative colitis induced by dextran sodium sulfate.

BACKGROUND: Sulfasalazine has been used as a standard-of-care in ulcerative colitis for decades, however, it results in severe adverse symptoms, such as hepatotoxicity, blood disorders, male infertility, and hypospermia. Accordingly, the new treatment strategy has to enhance pharmacological efficacy and stimultaneously minimize side effects. AIM: To compare the anti-inflammatory action of sulfasalazine alone or in combination with herbal medicine for ulcerative colitis in a dextran sodium sulfate (DSS)-induced colitis mouse model. METHODS: To induce ulcerative colitis, mice received 5% DSS in drinking water for 7 d. Animals were divided into five groups (n = 9 each) for use as normal (non-DSS), DSS controls, DSS + sulfasalazine (30 mg/kg)-treatment experimentals, DSS + sulfasalazine (60 mg/kg)-treatment experimentals, DSS + sulfasalazine (30 mg/kg) + Citrus unshiu peel and Bupleuri radix mixture (30 mg/kg) (SCPB)-treatment experimentals. RESULTS: The SCPB treatment showed an outstanding effectiveness in counteracting the ulcerative colitis, as evidenced by reduction in body weight, improvement in crypt morphology, increase in antioxidant defenses, down-regulation of proinflammatory proteins and cytokines, and inhibition of proteins related to apoptosis. CONCLUSION: SCPB may represent a promising alternative therapeutic against ulcerative colitis, without inducing adverse effects.

Protective Effects of Phellinus linteus Mycelium on the Development of Osteoarthritis after Monosodium Iodoacetate Injection.

OBJECTIVE: The aim of this study was to identify the protective effects of Phellinus linteus mycelium (PLM) and its possible mechanisms in a model of monosodium iodoacetate- (MIA-) induced osteoarthritis (OA). METHODS: Intra-articular injection of MIA was injected to 50 µL with 80 mg/mL using a 0.3 mL insulin syringe into the right knee joint. Changes in hindpaw weight-bearing distribution between the right (osteoarthritic) and left (contralateral control) legs were used as an index of joint discomfort. PLM (50, 100, and 200 mg/kg body weight) was orally administered once daily for 14 days from day 7 after MIA treatment. And then, various factors associated with inflammatory response and cartilage degeneration in cartilage tissues detected by western blotting. RESULTS: PLM treatment showed a concentration-dependent elevation in change in hindpaw weight-bearing distribution (HWBD). PLM200 demonstrated the capacity to significantly increase HWBD, indicating that the change in weight-bearing distribution means the reduction of spontaneous pain. Our results indicate that PLM suppressed the inflammatory factors via NF-κB signaling pathway induced by p38 phosporlyation. Moreover, PLM200 exhibited a significant reduction of ROS produced by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. PLM100 and PLM200 inhibited the levels of matrix metalloproteinase (MMP)-1, one of proteinase that degrades extracellular matrix (ECM). CONCLUSIONS: Taken together, our results indicated that PLM has a strong chondroprotective effect through the suppression both ROS production and inflammation.

Improvement of Inflammation through Antioxidant Pathway of Gardeniae Fructus 50% EtOH Extract (GE) from Acute Reflux Esophagitis Rats.

Gardeniae Fructus 50% EtOH extract (GE) is a traditional herb that has been used to treat a variety of diseases. In this study, we investigate the antioxidant, anti-inflammatory, and antiapoptotic properties of GE on acute reflux-induced esophagitis (RE) model in rats. 2,2'-Azino-bis (3-ethylbenzothiazolin-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays were performed to determine the antioxidant activity of GE. GE was given orally at 50 and 100 mg/kg body weight 1h 30 min prior to RE induction. And its effect was assessed in comparison with RE control and normal groups. The administration of the extract of the GE showed remarkable protection of mucosal damage in esophageal tissue, and the histologic observation showed that the gastric lesion was improved. Increased reactive oxygen species (ROS) levels in the serum were diminished by GE treatment. The antioxidative biomarkers including nuclear factor-erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) were significantly increased. GE administration significantly reduced the inflammatory protein expression through MAPK-related signaling pathways and the nuclear factor-kappa B (NF-κB) pathway. These results suggest that GE protects the esophagus mucosal membrane by attenuating oxidative stress and inflammatory response under reflux esophagitis condition through the antioxidant pathway. Therefore, it is suggested that GE may be a potential remedy for the treatment of reflux esophagitis.

Young Persimmon Fruit Extract Suppresses Obesity by Modulating Lipid Metabolism in White Adipose Tissue of Obese Mice.

Young persimmon fruit (YPF) has recently been reported to have a regulatory effect on lipid metabolism. The aim of this study was to investigate whether the YPF aqueous extract (YPFE) exert an antiobesity effect by modulating lipid metabolism in the white adipose tissue (WAT) of obese C57BLKS/J db/db mice. YPFE (100 or 200 mg/kg body weight/day) or distilled water as a vehicle was orally administered by gavage to 12-week-old obese male db/db mice for 3 weeks (n = 7 for each group). YPFE administration significantly reduced body weight and WAT size. Furthermore, YPFE considerably reduced triglyceride and cholesterol concentrations in serum and WAT. Obese vehicle treated mice exhibited an enhanced protein expression of adipogenic and lipogenic genes. However, this increased expression was alleviated in the YPFE-fed groups, resulting in inhibition of adipogenesis and downregulation of fatty acid synthesis. In addition, there was an increase in the level of transcription factors associated with fatty acid oxidation in the YPFE-treated group. In obese mice, the expression of proteins associated with cholesterol metabolism was augmented. YPFE did not affect cholesterol synthesis, but cholesterol efflux-related proteins were significantly upregulated. YPF exerts beneficial effects on obesity by inhibiting adipogenesis and reducing lipid synthesis and accumulation by regulation of lipid-related transcription factors in the WAT of obese mice.

Rice Hull Extract (RHE) Suppresses Adiposity in High-Fat Diet-Induced Obese Mice and Inhibits Differentiation of 3T3-L1 Preadipocytes.

Obesity is one of major health challenges in the industrial world. Although rice hull has been reported to show various bioactivities, no studies have evaluated its anti-obesity effect. We hope to demonstrate the anti-obesity effect of rice hull extract (RHE) and the underlying mechanism in high-fat diet (HFD)-induced obese mice and 3T3-L1 preadipocytes. Serum lipid profiles were determined by enzymatic methods. Histological analysis of liver and epididymis fat tissues was carried out with hematoxylin and eosin stain. The mRNA expression of adipogenic markers was analyzed with qRT-PCR and western blotting. Oral administration of RHE reduced body weight gain and fat accumulation in HFD-fed mice. RHE also reduced lipid accumulation by inhibiting the mRNA expression of adipogenic-related genes in HFD-fed obese mice and differentiated preadipocytes. The downregulation of adipogenesis by RHE was mediated through the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC). In addition, RHE induced the phosphorylation of c-Jun N-terminal kinases (JNK) and extracellular-signal-regulated kinases (ERK) in liver and epididymis adipose tissues of HFD-fed obese mice. Taken together, these findings indicate that RHE could inhibit the differentiation of adipose cell and prevent HFD-induced obesity, suggesting its potential in the prevention of obesity and metabolic syndrome and related-disorders.

Banha-sasim-tang improves gastrointestinal function in loperamide-induced functional dyspepsia mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: Banha-sasim-tang (BST; Hange-shashin-to in Kampo medicine; Banxia xiexin tang in traditional Chinese medicine) is a traditional Chinese harbal medicine that has been commonly used for gastrointestinal disorders. AIM OF THE STUDY: To investigate the pharmacological effects of BST, a standardized herbal drug, on main symptoms of functional dyspepsia including delayed gastric emptying, and underlying mechanisms of action in mouse model. METHODS AND MATERIALS: Balb/C mice were pretreated with BST (25, 50, 100 mg/kg, po) or mosapride (3 mg/kg, po) for 3 days, and then treated with loperamide (10 mg/kg, ip) after 19 h fasting. A solution of 0.05% phenol red (500 µL) or 5% charcoal diet (200 µL) was orally administered, followed by scarifying and assessment of gastric emptying or gastro-intestinal motility. C-kit (immunofluorescence), nNOS (western blot) and gastric contraction-related gene expression were examined in stomach tissue. RESULTS: The loperamide injection substantially delayed gastric emptying, while the BST pretreatment significantly attenuated this peristaltic dysfunction, as evidenced by the quantity of stomach-retained phenol red (p < 0.05 or 0.01) and stomach weight (p < 0.05 or 0.01). The BST pretreatment significantly tempered the loperamide-induced inactivation of c-kit and nNOS (p < 0.05 or 0.01) as well as the contraction-related gene expression, such as the 5HT4 receptor (5HT4R), anoctamin-1 (ANO1), ryanodine receptor 3 (RYR3) and smooth muscle myosin light chain kinase (smMLCK). The BST pretreatment also significantly attenuated the alterations in gastro-intestinal motility (p < 0.01). CONCLUSION: Our results are the first evidence of the prokinetic agent effects of Banha-sasim-tang in a loperamide-induced FD animal model. The underlying mechanisms of action may involve the modulation of peristalsis via activation of the interstitial cells of Cajal and the smooth muscle cells in the stomach.

Chemopreventive Effect of Aster glehni on Inflammation-Induced Colorectal Carcinogenesis in Mice.

Although Aster glehni is a common dietary herb that has various bioactivities, including anti-diabetic, anti-adipogenic, and anti-inflammatory effects, A. glehni has not been studied in colon cancer. Therefore, we hypothesized the chemopreventive effects of an ethanol extract of A. glehni (AG) on azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated cancer (CAC) in mice. In this study, we found that treatment with AG significantly attenuated the AOM/DSS-induced enlargement of the spleen and shortening of the colon. In addition, colonic tumor formation, colonic damage, and increased muscle thickness were significantly reduced in AOM/DSS-induced mice fed AG. Treatment with AG also reduced intestinal interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α production and decreased inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 protein expression in mice with AOM/DSS-induced CAC. Furthermore, AG reduced nuclear factor (NF)-κB activation via phosphorylation and degradation of inhibitor of kappa Bα (IκBα), leading to inhibition of NF-κB p65 nuclear translocation. It also downregulated the expression of NF-κB-related proteins, including the B-cell lymphoma 2 (Bcl-2) family and inhibitors of apoptosis proteins (IAPs), in mice with AOM/DSS-induced CAC. Taken together, these findings suggest that the treatment with AG inhibited colitis-associated colon carcinogenesis in mice, and this chemopreventive effect was strongly mediated by suppression of the NF-κB signaling pathway, indicating that AG could be a promising protective agent against CAC.

Low-Molecular-Weight Oligonol, a Polyphenol Derived from Lychee Fruit, Attenuates Experimental Reflux Esophagitis and HCl/Ethanol-Induced Gastric Ulcer.

Oligonol, a polyphenol derived from lychee fruit, is produced by an oligomerization process that converts high-molecular-weight polyphenol polymers into low-molecular-weight oligomers. Evidence suggests that oligonol exerts its beneficial effects based on antioxidant and anti-inflammatory properties. This study was the first to investigate the antioxidative and anti-inflammatory effects of oligonol on gastroesophageal inflammatory models: surgically induced acute reflux esophagitis (RE) and gastric ulcer (GU) induced by HCl/ethanol. In the in vitro study, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazolin-6-sulfonic acid) (ABTS) radical scavenging assays were performed to determine the antioxidant activity of oligonol. The experimental groups were each composed of normal, vehicle, and oligonol groups. RE rats and GU mice were treated orally with oligonol (100 mg/kg bw) or distilled water as a vehicle (n = 8 for each group). Oligonol exhibited potent free radical-scavenging capacities for DPPH and ABTS radicals, activities that were similar to those of ascorbic acid. The in vivo study revealed that oligonol consumption significantly prevented RE and GU formation and decreased the gross mucosal injury from oxidative stress. Oligonol decreased the reactive oxygen species levels and elevated levels of both inflammatory mediators and cytokines (p-IκB, NF-κBp65, COX-2, iNOS, TNF-α, and IL-1ß) in the RE and GU models. Oligonol had a protective effect against oxidative stress by regulating antioxidant enzyme (superoxide dismutase, catalase, and GPx-1/2) activities in GU mice. Oligonol has potential as a preventive and therapeutic agent for gastroesophageal inflammatory diseases, including RE and GU.