Proteomic studies of putative molecular signatures for biological effects by Korean Red Ginseng.

BACKGROUND: Korean Red Ginseng (KRG) has been widely used as an herbal medicine to normalize and strengthen body functions. Although many researchers have focused on the biological effects of KRG, more studies on the action mechanism of red ginseng are still needed. Previously, we investigated the proteomic changes of the rat spleen while searching for molecular signatures and the action mechanism of KRG. The proteomic analysis revealed that differentially expressed proteins (DEPs) were involved in the increased immune response and phagocytosis. The aim of this study was to evaluate the biological activities of KRG, especially the immune-enhancing response of KRG. METHODS: Rats were divided into 4 groups: 0 (control group), 500, 1000, and 2000 mg/kg administration of KRG powder for 6 weeks, respectively. Isobaric tags for relative and absolute quantitation was performed with Q-Exactive LC-MS/MS to compare associated proteins between the groups. The putative DEPs were identified by a current UniProt rat protein database search and by the Gene Ontology annotations. RESULTS: The DEPs appear to increase the innate and acquired immunity as well as immune cell movement. These results suggest that KRG can stimulate immune responses. This analysis refined our targets of interest to include the potential functions of KRG. Furthermore, we validated the potential molecular targets of the functions, representatively LCN2, CRAMP, and HLA-DQB1, by Western blotting. CONCLUSION: These results may provide molecular signature candidates to elucidate the mechanisms of the immune response by KRG. Here, we demonstrate a strategy of tissue proteomics for the discovery of the molecular function of KRG.

Korean Red Ginseng Extract Increases Apoptosis by Activation of the Noxa Pathway in Colorectal Cancer.

BACKGROUND: Although the anticancer activity of Korean Red Ginseng (KRG) has been known in various cancers, the mechanism of KRG-induced apoptosis is unknown in colorectal cancer (CRC). In our study, we examined whether KRG induces apoptosis in CRC cells. METHODS: In the cell viability assay, the concentration of the appropriate KRG extracts was fixed at 2.5 mg/mL in numerous CRC cells. This fixed concentration was in other experiments, and it was confirmed that the KRG extracts induce apoptosis in CRC cells. RESULTS: We found that KRG induced Noxa activation and apoptosis and increased endoplasmic reticulum stress via reactive oxygen species production. This indicated that KRG efficiently enhanced cell death in CRC cells. CONCLUSION: Our results show that KRG can be used as a possible anticancer drug for patients with CRC.

Obovatol inhibits NLRP3, AIM2, and non-canonical inflammasome activation.

BACKGROUND: Obovatol, a biphenolic chemical originating from Magnolia obovata, has been utilized as a traditional medicine for the treatment of inflammatory diseases. Inflammasome induces maturation of inflammatory cytokines in response to intracellular danger signals, and its dysregulation induces inflammatory diseases. PURPOSE: The effect of obovatol on inflammasome activation has not been reported, although its anti-inflammatory properties have been studied. STUDY DESIGN/METHODS: Obovatol was treated to macrophages with inflammasome triggers, and secretions of interleukin (IL)-1ß, IL-18, and caspase-1 were measured as readouts of inflammasome activation. In addition, Asc pyroptosome formation, caspase-1 activity, and mitochondrial reactive oxygen species (ROS) production were analyzed in mechanical studies. Anti-inflammasome properties of obovatol were confirmed in an animal model. RESULTS: Obovatol inhibited NLRP3, AIM2, and non-canonical inflammasomes through inhibition of Asc pyroptosome formation and mitochondrial ROS generation. In addition, obovatol disrupted the priming step of inflammasome activation and inhibited transcription of inflammatory cytokines. In mice, obovatol attenuated serum IL-1ß elevation in response to monosodium urate crystals. CONCLUSION: Obovatol is suggested as an inhibitor of NLRP3, AIM2, and non-canonical inflammasomes.

Subchronic oral toxicity study of Korean red ginseng extract in Sprague-Dawley rats with a 4-week recovery period.

Ginseng is a major herbal remedy used in Asian countries for thousands of years and known to restore and enhance vital energy. Korean red ginseng, which is processed by steaming and drying fresh Panax ginseng, is most popular and contains unique ginsenosides, which have anticancer and anti-inflammatory properties. The present study was carried out to evaluate the repeated oral dose toxicity of Korean red ginseng extract. The test article was administered orally once a day to male and female Sprague-Dawley rats at dose levels of 0, 500, 1000, or 2000 mg/kg/day for 13 consecutive weeks (15 animals/sex/group in the vehicle control and 2000 mg/kg/day groups, and 10 animals/sex/group in the 500 and 1000 mg/kg/day groups). Ten animals per group were sacrificed at the end of the 13-week treatment period, and the remaining rats were sacrificed after a 4-week recovery period. Administration of Korean red ginseng extract did not result in any toxicologically significant changes in mortality, body weight, food consumption, ophthalmoscopy, hematology, serum biochemistry, gross pathological findings, absolute/relative organ weights, or histopathology. It was established that the no observed adverse effect level (NOAEL) of the test article was 2000 mg/kg/day for both sexes in this study.

Korean red ginseng extracts inhibit NLRP3 and AIM2 inflammasome activation.

Korean red ginseng extract (RGE) is one of the most popular natural herbs modulating the immune system. Although the effects of RGE on immunity have been reported, its effects on inflammasomes, multi-protein complexes that activate caspase-1 to induce maturation of interleukin (IL)-1ß, have not been studied yet. In this study, we elucidated the effect of RGE on inflammasome activation using mouse and human macrophages. In our results, RGE inhibited IL-1ß maturation resulting from NLRP3 inflammasome activation in both in vitro and in vivo models. In addition, RGE strongly attenuated IL-1ß secretion as well as pathogen clearance via pyroptotic cell death by macrophages through inhibition of AIM2 inflammasome activation. Ginsenosides Rg1 and Rh3 were suggested as inhibitors of the inflammasome activation. Thus, we demonstrated that RGE inhibits both NLRP3 and AIM2 inflammasome activation, with predominant involvement of the AIM2 inflammasome.

Subacute oral toxicity study of korean red ginseng extract in sprague-dawley rats.

Ginseng is a well-known traditional medicine used in Asian countries for several thousand years, and it is currently applied to medicine, cosmetics, and nutritional supplements due to its many healing and energygiving properties. It is well demonstrated that ginsenosides, the main ingredient of ginseng, produce a variety of pharmacological and therapeutic effects on central nerve system (CNS) disorders, cardiovascular disease, endocrine secretions, aging, and immune function. Korean red ginseng extract is a dietary supplement containing ginsenoside Rb1 and ginsenoside Rg1 extracted from Panax ginseng. While the pharmacokinetics and bioavailability of the extract have been well established, its toxicological properties remain obscure. Thus, four-week oral toxicity studies in rats were conducted to investigate whether Korean red ginseng extract could have a potential toxicity to humans. The test article was administered once daily by oral gavage to four groups of male and female Sprague-Dawley (SD) rats at dose levels of 0, 500, 1,000, and 2,000 mg/kg/day for four weeks. Neither deaths nor clinical symptoms were observed in any group during the experiment. Furthermore, no abnormalities in body weight, food consumption, ophthalmology, urinalysis, hematology, serum biochemistry, gross findings, organ weights, or histopathology were revealed related to the administration of the test article in either sex of any dosed group. Therefore, a target organ was not determined in this study, and the no observed adverse effect level (NOAEL) of Korean red ginseng extract was established to be 2,000 mg/kg/day.