CGplus, a standardized herbal composition ameliorates non-alcoholic steatohepatitis in a tunicamycin-induced mouse model.

BACKGROUND: The prevalence of Non-alcoholic fatty liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH) has increased by 15-39% worldwide, but no pharmaceutical therapeutics exists. HYPOTHESIS/PURPOSE: This study investigated anti-hepatosteatotic effect of CGplus (a standardized herbal composition of Artemisia iwayomogi, Amomum xanthioides, and Salvia miltiorrhiza) and its underlying mechanisms in a tunicamycin-induced NASH model. METHODS: C57/BL6J male mice were orally administrated CGplus (50, 100, or 200 mg/kg), dimethyl dimethoxy biphenyl dicarboxylate (DDB, 50 mg/kg) or distilled water daily for 5 days. 18 h after a single injection of tunicamycin (ip, 2 mg/kg), the parameters for hepatic steatosis and inflammation were measured. RESULTS: Pretreatment with CGplus significantly attenuated the accumulation of triglycerides and total cholesterol as well as lipid peroxidation, evidenced by quantitative and histopathological analyses in liver tissues. The elevations of serum aspartate transaminase, alanine transaminase and lactate dehydrogenase were significantly ameliorated by CGplus. Also, it normalized the altered activities of pro- (TNF-α, IL-1ß and IL-6), anti-inflammatory (IL-10) cytokines and lipid metabolism-related molecules in protein and gene expression analyses. CONCLUSION: Our data present experimental evidence for the potential of CGplus as an herbal therapeutic against NAFLD and NASH. Its underlying mechanisms may involve the modulations of pro- and anti-inflammatory cytokines, but further study is required especially for the actions of CGplus on lipid metabolisms.

Honeybee (Apis mellifera) Venom Reinforces Viral Clearance during the Early Stage of Infection with Porcine Reproductive and Respiratory Syndrome Virus through the Up-Regulation of Th1-Specific Immune Responses.

Porcine reproductive and respiratory syndrome (PRRS) is a chronic and immunosuppressive viral disease that is responsible for substantial economic losses for the swine industry. Honeybee venom (HBV) is known to possess several beneficial biological properties, particularly, immunomodulatory effects. Therefore, this study aimed at evaluating the effects of HBV on the immune response and viral clearance during the early stage of infection with porcine reproductive and respiratory syndrome virus (PRRSV) in pigs. HBV was administered via three routes of nasal, neck, and rectal and then the pigs were inoculated with PRRSV intranasally. The CD4+/CD8+ cell ratio and levels of interferon (IFN)-γ and interleukin (IL)-12 were significantly increased in the HBV-administered healthy pigs via nasal and rectal administration. In experimentally PRRSV-challenged pigs with virus, the viral genome load in the serum, lung, bronchial lymph nodes and tonsil was significantly decreased, as was the severity of interstitial pneumonia, in the nasal and rectal administration group. Furthermore, the levels of Th1 cytokines (IFN-γ and IL-12) were significantly increased, along with up-regulation of pro-inflammatory cytokines (TNF-α and IL-1ß) with HBV administration. Thus, HBV administration-especially via the nasal or rectal route-could be a suitable strategy for immune enhancement and prevention of PRRSV infection in pigs.

Poly D,L-lactide-co-glycolide (PLGA) nanoparticle-encapsulated honeybee (Apis melifera) venom promotes clearance of Salmonella enterica serovar Typhimurium infection in experimentally challenged pigs through the up-regulation of T helper type 1 specific immune responses.

Honeybee (Apis melifera) venom (HBV), which includes melittin and lipid-soluble ingredients (chrysin and pinocembrin), elicited increases in the CD4(+)/CD8(+) T lymphocyte ratio, relative mRNA expression levels of the T helper type 1 (Th 1) cytokines (interferon-γ and IL-12) and reinforced viral clearance of an experimental porcine reproductive and respiratory syndrome (PRRS) virus infection in our previous study. On the basis of that previous study, we have now developed poly-d,l-lactide-co-glycolide (PLGA)-encapsulated HBV nanoparticles (P-HBV) for longer sustained release of HBV. We administered P-HBV to pigs via the rectal route, and then evaluated the potential immune-enhancing and bacterial clearance effects of P-HBV against Salmonella enterica serovar Typhimurium. The CD4(+)/CD8(+) lymphocyte ratio, proliferative capacity of peripheral blood lymphocytes and relative mRNA expression levels of IFN-γ and IL-12 (produced mainly by Th1 lymphocytes) were significantly increased in the P-HBV group up to 2 weeks post-administration of P-HBV. After S. Typhimurium infection, the P-HBV group showed a marked reduction in microbial burden in feces and all tissue samples (including the ileum, cecum, colon, and mesenteric lymph node (MLN)), a significant increase in Th 1 cytokines (IFN-γ, IL-2, and IL-12) and a marked decrease in a Th 2 cytokine (IL-4) in all tissue samples and peripheral blood lymphocytes. Thus, P-HBV may be a promising strategy for immune enhancement and prevention of S. Typhimurium or other bacterial infections.

Immunoprophylactic effects of administering honeybee (Apis melifera) venom spray against Salmonella gallinarum in broiler chicks.

Antibiotics continue to be used as growth promoters in the poultry industry. Honeybee (Apis melifera) venom (HBV) possesses a number of beneficial biological activities, particularly for regulating the immune system. The aim of the present study was to evaluate the immunoprophylactic effects of HBV against Salmonella Gallinarum in broiler chicks as an initial step towards developing eco-friendly alternatives to reduce antibiotic use. HBV was administered using a spray technique. HBV improved body weight gain, particularly in the presence of infection. Moreover, HBV enhanced antibody production activity against formalin-killed S. Gallinarum. The CD4(+):CD8(+) T lymphocyte ratio, relative mRNA expression levels of interleukin-18 and interferon-γ, and serum lysozyme activity also increased following HBV administration before the infection period as well as during infection. HBV reinforced bacterial clearance and increased survivability against S. Gallinarum. Corresponding pathological analyses demonstrated that the HBV-sprayed group displayed mild and less severe abnormal changes compared with those in the control group. It was presumed that the prophylactic effects of HBV against S. Gallinarum were associated with its non-specific immune response stimulating activity. Thus, HBV may provide an alternative to reduce antibiotic use in the poultry industry.

Suppression of the onset and progression of collagen-induced arthritis by chebulagic acid screened from a natural product library.

OBJECTIVE: Chebulagic acid (CHE) from the immature seeds of Terminalia chebula was identified from a natural product library as a potent suppressor of T cell activity. This study examined the effectiveness of CHE against the onset and progression of collagen-induced arthritis (CIA) in mice. METHODS: Arthritis was induced in DBA/1J mice by subcutaneous immunization with bovine type II collagen on days 0 and 21. CHE was administered intraperitoneally for 3 weeks, either as prophylaxis (10 or 20 mg/kg) before disease onset or as therapy (20 mg/kg) after disease onset. Clinical scores, serum antibody levels, and cytokines were measured, and flow cytometric analysis and real-time reverse transcription-polymerase chain reaction were performed to evaluate the knee joints of mice with CIA. RESULTS: In both the prophylactic and therapeutic CHE dosing models, all clinical scores, serum levels of total and anticollagen IgG, and levels of interleukin-10 (IL-10) and IL-6 were reduced, while serum levels of transforming growth factor beta (TGFbeta) were markedly elevated. The number of granulocytes was reduced, but the proportion of CD4+,CD25+ T cells was greater in the knee joints of CHE-treated CIA mice. Expression of Foxp3 and TGFbeta messenger RNA was also augmented significantly in the knee joints of CHE-treated CIA mice in the therapeutic dosing model. CONCLUSION: CHE significantly suppressed the onset and progression of CIA in mice. Immune suppression via the induction of TGFbeta and CD4+,CD25+ T cells may represent a new strategy in the development of therapies for managing rheumatoid arthritis and other inflammatory diseases.