Apple Pomace Extract Improves Endurance in Exercise Performance by Increasing Strength and Weight of Skeletal Muscle.

Ursolic acid is a lipophilic pentacyclic triterpenoid found in many fruits and herbs and is used in several herbal folk medicines for diabetes. In this study, we evaluated the effects of apple pomace extract (APE; ursolic acid content, 183 mg/g) on skeletal muscle atrophy. To examine APE therapeutic potential in muscle atrophy, we investigated APE effects on the expression of biomarkers associated with muscle atrophy and hypertrophy. We found that APE inhibited atrophy, while inducing hypertrophy in C2C12 myotubes by decreasing the expression of atrophy-related genes and increasing the expression of hypertrophy-associated genes. The in vivo experiments using mice fed a diet with or without APE showed that APE intake increased skeletal muscle mass, as well as grip strength and exercise capacity. In addition, APE significantly improved endurance in the mice, as evidenced by increased exhaustive running time and muscle weight, and reduced the expression of the genes involved in the development of muscle atrophy. APE also decreased the concentration of serum lactate and lactate dehydrogenase, inorganic phosphate, and creatinine, the indicators of accumulated fatigue and exercise-induced stress. These results suggest that APE may be useful as an ergogenic functional food or dietary supplement.

Reduction of interleukin-1ß induced matrix metalloproteinase-3 release by extracts of six plants: inhibitory screening of 35 traditional medicinal plants.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease associated with matrix metalloproteinase (MMP)-3, leading to destruction of the cartilage. The objective of this study was to investigate and discuss the suitability of the 35 medicinal plants as therapeutic candidates to treat RA. Fibroblast-like synoviocytes (FLSs), derived from patients with RA, were adjusted to 2 × 10(6) cells/mL in a 24-well plate and pretreated with the distilled water extracts of the 35 plants (1, 10, and 100 µg/mL) for 1 h followed by interleukin-1ß (IL-1ß) (1 ng/mL) for 24 h. The concentration of MMP-3 was then determined using a Duoset ELISA Kit. The six plants (Artemisiae Capillaris Herba, AC; Bambusae Caulis In Taeniam, BC; Cassiae Semen, CS; Corni Fructus, CF; Leonuri Herba, LH; Schizonepetae Spica, SS) showed no toxicity, including MMP-3. The MMP-3 level was increased by 3.38-fold (212.23 µg/mL) in IL-1ß-stimulated FLSs. The IL-1ß-induced MMP-3 level was significantly and dose-dependently reduced by >50% by the six plants (P < 0.01: at 100  µg/ mL of CS and LH, P < 0.001: at 10 µg/mL of all plants, and at 100 µg/mL of AC, BC, CF, and SS). This is the first study on the MMP-3 inhibitory effect of the examined plants in FLSs isolated from RA patients. From our original research, the six candidate plants were identified.

Extracts from Citrus unshiu promote immune-mediated inhibition of tumor growth in a murine renal cell carcinoma model.

AIM OF THIS STUDY: Citrus unshiu (Satsuma mandarin, SM) is a citrus fruit the peel of which has been used as a traditional Chinese medicine to treat common cold, relieve exhaustion, and cancer. In this study, we examined how effectively the content and peel extracts of SM can suppress cancer growth. The mechanism underlying cancer-suppressing properties of SM was investigated in tumor-bearing mice with renal carcinoma cell, Renca. MATERIALS AND METHODS: Effectiveness of SM in tumor suppression was evaluated by measuring size of tumor mass in tumor-bearing mice treated with various doses of SM content and peel extracts. Proliferation of tumor cells and splenocytes was determined by MTT assay and [³H]TdR uptake, respectively. Relevant immunological mechanisms were chased by assaying cytokines including TGF-ß, IL-6, IFN-γ, and TNF-α by ELISA. RESULTS: The content and peel extracts of SM inhibited the growth of tumor cells in tumor-bearing mice. Especially, average tumor volume of two groups treated with 3 and 30 mg peel extracts per mouse weight (kg) were significantly decreased to 52.32% (p<0.05) and 68.72% (p<0.01), respectively. To identify tumor regression mechanism, anti-tumor cytokines measured in Con A-activated splenocytes from tumor-bearing mice. IFN-γ was increased in both of the peel extract-treated groups, while TNF-α, which had been decreased by tumor growth, was rescued to the normal level in SM content and peel extracts-treated groups. However, SM content and peel extracts did not inhibit proliferation and tumor-proliferative cytokines including TGF-ß and IL-6 production of tumor cells. CONCLUSION: These results indicate that SM content and peel extracts have anti-tumor properties in the tumor-bearing murine model. The mechanism underlying the anti-tumor effects of SM extracts is strongly suggested to be via boosting cytokines such as IFN-γ and TNF-α, enhancing immune-mediated anti-tumor properties.

An Angiotensin I converting enzyme polymorphism is associated with clinical phenotype when using differentiation-syndrome to categorize korean bronchial asthma patients.

In this study, genetic analysis was conducted to investigate the association of angiotensin I converting enzyme (ACE) gene polymorphism with clinical phenotype based on differentiation-syndrome of bronchial asthma patients. Differentiation-syndrome is a traditional Korean medicine (TKM) theory in which patients are classified into a Deficiency Syndrome Group (DSG) and an Excess Syndrome Group (ESG) according to their symptomatic classification. For this study, 110 participants were evaluated by pulmonary function test. Among them, 39 patients were excluded because they refused genotyping. Of the remaining patients, 52 with DSG of asthma (DSGA) and 29 with ESG of asthma (ESGA), as determined by the differentiation-syndrome techniques were assessed by genetic analysis. ACE insertion/deletion (I/D) polymorphism analysis was conducted using polymerase chain reaction (PCR). Student's t, chi-square, Fisher and Hardy-Weinberg equilibrium tests were used to compare groups. No significant differences in pulmonary function were observed between DSGA and ESGA. The genotypic frequency of ACE I/D polymorphism was found to differ slightly between DSGA and ESGA (P = .0495). However, there were no significant differences in allelic frequency observed between DSGA and ESGA (P = .7006, OR = 1.1223). Interestingly, the allelic (P = .0043, OR = 3.4545) and genotypic (P = .0126) frequencies of the ACE I/D polymorphism in female patients differed significantly between DSGA and ESGA. Taken together, the results presented here indicate that the symptomatic classification of DSGA and ESGA by differentiation-syndrome in Korean asthma patients could be useful in evaluation of the pathogenesis of bronchial asthma.

Bambusae Caulis in Taeniam extract reduces ovalbumin-induced airway inflammation and T helper 2 responses in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Bambusae Caulis in Taeniam (BC) was known as traditional herbal medicine with anti-inflammatory property in the Orient. AIM OF THE STUDY: Allergic asthma is inflammatory disease of airways associated with enhanced T helper (Th) 2 lymphocytes responses to allergens, leading to eosinophilic infiltration and elevated serum IgE levels. Although there were some studies that BC extract had an anti-inflammatory property, there was no study on asthma. In present study, we investigated the suitability of BC extract as a therapeutic candidate in the treatment of allergic airway disease in ovalbumin-induced asthma model. MATERIALS AND METHODS: Balb/C mice (female, 6 weeks old) were treated by ovalbumin sensitization and nebulization, and used as asthma model. The number of eosinophil in bronchoalveolar lavage (BAL) fluid and the degree of eosinophila were investigated by hematoxylin and eosin stain and the infiltration of inflammatory cells into lung tissues was examined by staining by hematoxylin and eosin solution. The levels of interleukin (IL)-4 in BAL fluid, immunoglobulin E (IgE) in serum, interferon (IFN)-gamma and IL-4 production in splenocyte culture from Balb/C mice (not treated, 6 weeks old) that incubated with or without BC extract for 48 h were determined by enzyme-linked immunosorbent assay. RESULTS: The level of eosinophils was decreased by treatment of the animals with BC extract (40 mg/kg) and correspondingly, a significantly lowered degree of eosinophila was also reported (p<0.01). In lung tissue, BC extract reduced the increased immune cell infiltration induced by OVA (p<0.05). Furthermore, the levels of IL-4 and IgE in BAL fluid or serum up-regulated by OVA was decreased by BC extract. Finally, IFN-gamma production was significantly increased (p<0.01), while IL-4 production significantly decreased (p<0.01), after treatment of the culture supernatants of splenocytes with BC extract. CONCLUSIONS: These results indicated that BC extract reduces OVA-induced airway inflammation and Th 2 response in mice, suggesting that BC extract can be a therapeutic candidate for allergic airway disease, including asthma.

Inhibitory effect of Agrimoniae Herba on lipopolysaccharide-induced nitric oxide and proinflammatory cytokine production in BV2 microglial cells.

OBJECTIVES: Agrimoniae Herba has been used as an anti-inflammatory agent in traditional medicine. Nitric oxide and proinflammatory cytokines produced by activated microglia may be a possible etiological factor of neurodegenerative disorders. We evaluated whether Agrimoniae Herba could have an anti-inflammatory effect on lipopolysaccharide-induced BV2 microglial cells. METHODS: The effects of Agrimoniae Herba on lipopolysaccharide-induced nitric oxide and proinflammatory cytokine production in BV2 microglial cells were evaluated by nitric oxide assay, enzyme-linked immunosorbent assay and western blotting. RESULTS: Agrimoniae Herba had no cytotoxicity and suppressed lipopolysaccharide-induced nitric oxide production in BV2 microglial cells. Agrimoniae Herba also suppressed lipopolysaccharide-induced production of proinflammatory cytokines such as tumor necrosis factor, interleukin 1 beta and interleukin 6 in a dose-dependent manner. Agrimoniae Herba inhibited the expression of inducible nitric oxide synthase. DISCUSSION: Taken together, these findings indicate that Agrimoniae Herba may be used as a form of pharmaceutical acupuncture therapy in the treatment of brain inflammation.

Panax ginseng C.A. Meyer modulates the levels of MMP3 in S12 murine articular cartilage cell line.

AIM OF THE STUDY: The destruction of cartilage in patients with osteoarthritis occurs due to an imbalance between matrix synthesis and degradation. Cartilage degradation is induced by the activation of matrix metalloproteinases (MMPs). Therefore, this study was conducted to evaluate the cartilage protective effect of Panax ginseng C.A. Meyer (PG). MATERIALS AND METHODS: S12 cells were treated with various concentrations of extract of PG and gensenosides Rd and Rb(3) for 3h, after which 10 ng/ml interleukin-1beta (IL-1beta) was added to the culture media. The levels of MMP3 in the conditioned media were then evaluated using an enzyme-linked immunosorbent assay (ELISA). In addition, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to evaluate the mRNA expression of Type II Collagen and Pro-collagenase. Furthermore, Western blot analysis was performed to identify the roles that PG played in the ERK and p38 signaling pathways. RESULTS: The MMP3 secretion levels of S12 cells were significantly lowered in response to treatment with PG and gensenosides Rd and Rb(3) at a concentration of 100 microg/ml when compared to cells that were treated with IL-1beta. In addition, PG induced the mRNA expression of Type II Collagen dose dependently. Furthermore, phosphorylated p38 and ERK were detected in S12 articular cartilage cell line that was treated with IL-1beta. PG decreased the phosphorylation of p38, but PG did not exert any effect on phospho-ERK. CONCLUSIONS: These findings indicate that PG and gensenosides Rd and Rb(3) suppress MMP3 secretion and that gensenosides Rd and Rb(3) are the major elements involved in the suppression of MMP3 by PG. Furthermore, the suppression of MMP3 by PG occurs via the inhibition of phospho-p38 activation. Therefore, PG may exert a protective effect against the cartilage degradation of OA.