SBT (Composed of Panax ginseng and Aconitum carmichaeli) and Stigmasterol Enhances Nitric Oxide Production and Exerts Curative Properties as a Potential Anti-Oxidant and Immunity-Enhancing Agent.

Immune dysregulation is a risk factor for several diseases, including infectious diseases. Immunostimulatory agents have been used for the treatment of immune dysregulation, but deleterious adverse effects have been reported. The present study aims to establish the anti-oxidant and immunity-enhancing effects of Sambu-Tang (SBT), composed of Panax ginseng and Aconitum carmichaeli, and stigmasterol (Stig), an active compound of SBT. Immune-related factors were analyzed in RAW264.7 macrophage cells, mouse primary splenocytes, and the serum and spleen of cyclophosphamide-induced immunosuppressed mice. Results showed that the production levels of nitric oxide (NO) and expression levels of inducible NO synthase and heme oxygenase-1 were increased following SBT or Stig treatment in RAW264.7 cells. SBT or Stig increased the production levels of G-CSF, IFN-γ, IL-12, IL-2, IL-6, and TNF-α and induced the activation of NF-κB in RAW264.7 cells. SBT or Stig promoted splenic lymphocyte proliferation and increased splenic NK cell cytotoxic activity. In addition, SBT or Stig enhanced the levels of IFN-γ, IL-12, IL-2, IL-6, or TNF-α in the serum and spleen of the immunosuppressed mice. SBT or Stig increased the superoxide dismutase activity in the spleen. Collectively, SBT and Stig possess anti-oxidant and immunomodulatory activities, so they may be considered effective natural compounds for the treatment of various symptoms caused by immune dysregulation.

A mixture of Panax ginseng and Scrophularia buergeriana improves immune function in an immunosuppressed murine model.

BACKGROUND: Immunomodulatory drugs are currently used for immunosuppressed individuals, but adverse side effects have been reported. Although Panax ginseng and Scrophularia buergeriana are known to have respective pharmacological properties, the potential of a mixture of Panax ginseng and Scrophularia buergeriana (Isam-Tang, IST) as an immunomodulatory drug has not yet been studied. PURPOSE: The present study was designed to assess the immunomodulatory activity of IST and p-coumaric acid (pCA), an active compound of IST, in the immune system. METHODS: The levels of immunostimulatory cytokines, nitrite, inducible nitric oxide synthase (iNOS), NF-kB activation, and proliferation were examined in RAW264.7 cells, primary splenocytes and splenic NK cells isolated from normal mouse spleen, and in cyclophosphamide-induced immunosuppressed mice using ELISA, quantitative real-time PCR, Western blotting, and immunofluorescence staining. RESULTS: IST or pCA treatment increased the production of immunostimulatory cytokines and nitrite and the expression of iNOS in RAW264.7 cells and splenocytes. IST or pCA also induced NF-κB signaling activation and promoted the phagocytic activity of RAW264.7 cells. In addition, the splenocyte proliferation and splenic NK activity were enhanced by IST or pCA. IST or pCA increased the levels of immunostimulatory cytokines in immunosuppressed mice and ameliorated splenic tissue damage. CONCLUSION: These findings suggest that IST supplementation may be used to enhance immune function.

The immune-enhancing effects of a mixture of Astragalus membranaceus (Fisch.) Bunge, Angelica gigas Nakai, and Trichosanthes Kirilowii (Maxim.) or its active constituent nodakenin.

ETHNOPHARMACOLOGICAL RELEVANCE: A mixture (SH003) of Astragalus membranaceus (Fisch.) Bunge, Angelica gigas Nakai, and Trichosanthes Kirilowii (Maxim.) has beneficial effects against several carcinomas. There have been few reports on an immune-enhancing activity of SH003 and its active constituent nodakenin. AIM OF THE STUDY: This study aimed at identifying the immune-enhancing effect of SH003 and nodakenin. MATERIALS AND METHODS: The immune-enhancing effect was evaluated using RAW264.7 macrophages, mouse primary splenocytes, and a cyclophosphamide (CP)-induced immunosuppression murine model. RESULTS: The results show that SH003 or nodakenin stimulated the production levels of granulocyte colony-stimulating factor, IL-12, IL-2, IL-6, TNF-α, and nitric oxide (NO) and the expression levels of iNOS in RAW264.7 macrophages. SH003 or nodakenin also enhanced NF-κB p65 activation in RAW264.7 macrophages. SH003 or nodakenin stimulated the production levels of IFN-γ, IL-12, IL-2, TNF-α, and NO and the expression levels of iNOS in splenocytes. SH003 or nodakenin increased the splenic lymphocyte proliferation and splenic NK cell activity. In addition, SH003 or nodakenin increased the levels of IFN-γ, IL-12, IL-2, IL-6, and TNF-α in the serum and spleen of CP-treated mice, alleviating CP-induced immunosuppression. CONCLUSION: Taken together, the results of this study show that SH003 improved immunosuppression through the activation of macrophages, splenocytes, and NK cells. These findings suggest that SH003 could be applied as a potential immunostimulatory agent for a variety of diseases caused or exacerbated by immunodeficiency.

Dendropanax morbifera Leaf Extracts Improved Alcohol Liver Injury in Association with Changes in the Gut Microbiota of Rats.

This study evaluated the protective effects of Dendropanax morbifera leaf (DML) extracts in the liver due to excessive ethanol consumption. Our results showed that the ethanol extract had better antioxidant activity than the water extract, likely due to the higher levels of total flavonoid and phenolic compounds in the former. We found that the main phenolic acid was chlorogenic acid and the major flavonoid was rutin. Results from the animal model experiment showed concentration-dependent liver protection with the distilled water extract showing better liver protection than the ethanol extract. Gut microbiota dysbiosis induced by alcohol consumption was significantly shifted by DML extracts through increasing mainly Bacteroides and Allobaculum. Moreover, predicted metabolic activities of biosynthesis of beneficial monounsaturated fatty acids such as oleate and palmitoleate were enhanced. Our results suggest that these hepatoprotective effects are likely due to the increased activities of antioxidant enzymes and partially promoted by intestinal microbiota shifts.

Anti-Melanoma Activities and Phytochemical Compositions of Sorbus commixta Fruit Extracts.

Sorbus commixta Hedl. (Rosaceae family) has a long history as a medicinal plant in East Asian countries. In this study, we evaluated the effect of S. commixta fruit extracts prepared with different ethanol concentrations on anti-melanoma activity, and the extraction yield of phenolic compounds and flavonoids. Using the partitioned fractions from the EtOH extract, we found that the butanol fraction (BF) possessed strong cytotoxic activity against SK-MEL-2 cells (human melanoma cells) but not against HDFa cells (human dermal fibroblast adult cells). Additionally, BF-induced cell death was mediated by the inhibition of the mitogen-activated protein kinase/extracellular regulated kinase (MEK/ERK) signaling pathway, coupled with the upregulation of caspase-3 activity in SK-MEL-2 cells. Furthermore, HPLC analysis of polyphenolic compounds suggested that S. commixta fruits contained several active compounds including chlorogenic acid, rutin, protocatechuic acid, and hydroxybenzoic acid, all of which are known to possess anti-cancer activities. Although this study has been carried out by cell-based approach, these results suggest that S. commixta fruits contain promising anti-melanoma compounds.

Dendropanax morbifera Leaf Polyphenolic Compounds: Optimal Extraction Using the Response Surface Method and Their Protective Effects against Alcohol-Induced Liver Damage.

The response surface methodology was used to optimally extract the antioxidant substances from Dendropanax morbifera leaves. The central composite design was used to optimally analyze the effects of ethanol concentration, sample to solvent ratio, extraction temperature, and extraction time on the total flavonoids (TF) content, ferric reducing antioxidant power (FRAP), and Trolox equivalent antioxidant capacity (TEAC). All three parameters were largely influenced by the ethanol concentration and extraction temperature, while TEAC was also influenced by the sample to solvent ratio. The maximum values of TF content, FRAP, and TEAC were achieved under the following extraction conditions: 70% ethanol, 1:10 sample to solvent ratio, 80 °C, and 14 h. The D. morbifera leaf extracts (DMLE) produced under these optimum extraction conditions were investigated to determine their preventive effects on alcohol-induced liver injury. The DMLE was shown to prevent liver injury by scavenging the reactive oxygen species generated by alcohol. In addition, composition analysis of DMLE found high contents of chlorogenic acid and rutin that were determined to inhibit alcoholic liver injury. The findings of this study suggest that DMLE could prove useful as a functional food product supplement to prevent liver injury caused by excessive alcohol consumption.