1 The present work was performed to investigate the effects of ginsenoside Rh2 on proliferation, cell cycle-regulation and differentiation of human leukemia HL-60 cells as well as the underlying mechanisms for these effects. 2 Ginsenoside Rh2 potently inhibited the proliferation of HL-60 cells in both a dose- and time-dependent manner with an $IC_{50}$, $20{\mu}M$. 3 DNA flow-cytometry indicated that ginsenoside Rh2 markedly induced a $G_1$ phase arrest of HL-60 cells. 4 Among the $G_1$ phase cell cycle-related proteins, the levels of cyclin-dependent kinase(CDK)4, 6 and cyclin D1, cyclin D2, cyclin D3 were reduced by ginsenoside Rh2, whereas the steadystate levels of CDK2 and cyclin E were unaffected. 5 The protein levels of a CDK inhibitor p16, $p21^{CIP1/WAF1}$ and $p27^{KIP1}$ were markedly increased by ginsenoside Rh2. 6 Ginsenoside Rh2 markedly enhanced the binding of $p21^{CIP1/WAF1}$ and $p27^{KIP1}$ with CDK2 and CDK6, resulting in the reduced activity of both kinases and the hypophosphorylation of Rb protein. 7 We furthermore suggest that ginsenoside Rh2 is a potent inducer of the differentiation of HL-60 cells, based on observations such as a reduction of the nitroblue tetrazolium level, an increase in the esterase activities and phagocytic activity, morphology changes, and the expression of CD11b, CD14, CD64 and CD66b surface antigens. 8 In conclusion, the onset of ginsenoside Rh2-induced the $G_0/G_1$ arrest of HL-60 cells prior to the differentiation is linked to a sharp up-regulation of the $p21^{CIP1/WAF1}$ level and a decrease in the CDK2, CDK4 and CDK6 activities. This is the first report demonstrating that ginsenoside Rh2 potently inhibits the proliferation of human promyelocytic HL-60 cells via the $G_1$ phase cell cycle arrest and differentiation induction.

다양한 연구에 따르면, 고려인삼은 허약한 체질, 숙취, 폐경과 월경불순, 초기 당뇨병, 영양실조, 빈혈 및 단백질 부족, 간기능 악화, 각종 독성물질에 기인한 중독, 피로, 추위, 스트레스, 산후조리, 체력쇠퇴 등에 효능이 있음이 알려져 있다. 특히 고려인삼은 혈관 기능을 효과적으로 조절함으로 고혈압, 뇌졸중, 심근경색, 동맥경화, 관절염, 당뇨, 비만 등의 질환을 효과적으로 치료하거나 예방할 수 있는 효능이 있음이 최근 연구에 의하여 밝혀지고 있다. 그러나 고려인삼 약리효능의 표적분자(target molecule)나 생화학적 작용기전(biochemical mechanism)이 세포 및 분자 수준에서 규명되지 못하여 고려인삼이 의약품으로 인정받지 못하고 건강식품으로 분류되고 있어 소비가 한인 흑인 히스패닉 시장에 한정되고 있고, 최근에는 타 경쟁국 인삼에 비해 수출 경쟁력이 약화되고 있는 실정이다. 본 연구에서는 고려인삼 추출물과 효능성분이 혈관내피세포 기능조절에 미치는 효능 및 작용기전을 규명하여 고려인삼이 호발성 혈관질환에 대한 예방 및 치료 효능이 있음을 분자 및 유전자 수준에서 확인하고자 하였다.

To investigate the association between Korean red ginseng (KRG) intake in HIV-1 infected patients and occurrence of grossly deleted nef genes ($g{\Delta}nef$), we characterized nef genes in 10 long-term slow progressors (LTSP) infected with HIV-1 subtype B and 34 control patients. LTSP was defined whose the annual decrease in CD4 T cells was less than $20/{\mu}l$ over 10 years in the absence of antiretroviral therapy. They were treated with KRG for a prolonged period. Nef genes were amplified from peripheral blood mononuclear cells (PBMC) using nested PCR and products were sequenced directly. Patient CD4 T cell counts decreased from $444{\pm}207/{\mu}l$ to $294{\pm}177/{\mu}l$ over $136{\pm}23$ months of KRG intake. This corresponds to an annual decrease in the level of CD4 T cells of $13.3/{\mu}l$. A total of 479 nef genes were amplified from 137 PBMC samples. Nine out of the 10 patients, 47 (34.3%) out of the 137 samples, and 92 out of the 479 genes revealed $g{\Delta}nef$. The deletion extended outside the nef gene in 25 $g{\Delta}nef$ obtained from 6 patients. The proportion of samples with $g{\Delta}nef$ (34.3%) was significantly higher than 4.8% in control patients (P<0.001). In addition, it significantly increased as the duration of KRG intake prolongs (P<0.01). These data suggest the possibility that occurrence of $g{\Delta}nef$ might be associated with long-term intake of KRG.

Red ginseng is a classical traditional Chinese medicine. Among Chinese herbs, red ginseng has been considered as one of the tonics. Many studies indicated that red ginseng could enhance immune function of the human body. Red ginseng total saponin, ginsenoside, the most important active constituents identified in red ginseng can protect against myocardial ischaemia damage and protect endothelium against electrolysis-induced free radical injury. Macrophages play a significant role in host defense mechanisms. When activated, they inhibit the growth of a wide variety of tumor cells. The aim of this study was to determine the effects of pure ginsenoside Rb1 on immunostimulatory activity such as murine macrophage phagocytosis and proliferation of splenocytes. Furthermore, we investigated the effects of ginsenoside Rb1 on the production of nitric oxide (NO), reactive oxygen species (ROS) and proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) in murine macrophage, RAW 264.7 cells. ROS have emerged as important signaling molecules in the regulation of various cellular processes. Ginsenoside Rb1 significantly increased production of ROS in dose dependent manner. As NO plays an important role in immune function, ginsenoside Rb1 treatment could modulate several aspects of host defense mechanisms due to stimulation. Treatment with ginsenoside Rb1 to macrophages induced the production of NO and proinflammatory cytokines and expression levels of these genes in a dose-dependent manner. Furthermore, incubation of RAW 264.7 cells with ginsenoside Rb1 showed a dose dependent increased phagocytosis activity and lymphocyte proliferation of splenocytes. Therefore, these results suggest that ginsenoside Rb1 has promising potential as a natural medicine for stimulation of the immune system.

Purpose: Panaxadiols are more potent than panaxatriols as far as insulin secretory activity is concerned. In this study, we examined insulin secretory activity and mechanism of compound K (CK), a major intestinal bacterial metabolite of ginsenosides. Method: Insulin secretory activity of CK was examined using pancreatic beta cells and in Oral Glucose Tolerance Test assay. In addition, insulin secretory mechanism was studied in terms of calcium dependent or independent pathways. Results: In vitro, CK enhanced the insulin secretion concentration-dependently when compared to glucose-stimulated control cells. Insulin secretory mechanism of CK seems to block ATP sensitive K channels, which was confirmed by diazoxide (K channel opener) but, insulin resistance ameliorating activity of CK can't be ruled out. In vivo, CK showed hypoglycemic effect in OGTT.

In this study we examined the potential for the synergistic augmentation of the activity of inflammatory mouse peritoneal macrophages by stimulation with RGAP combined with IFN-$\gamma$. The moderate augmentative effect induced by preincubation with RGAP was observed in the production of IL-1, IL-6 and NO but not TNF-$\alpha$. In addition, IFN-$\gamma$ had a low activating effect. Following preincubation with both RGAP A and IFN-$\gamma$, a marked enhancement of secretory activity and tumoricidal activity was noted in mouse peritoneal macrophages. Treatment of peritoneal macrophage with combination increased the generation of IL-1, IL-6, TNF-$\alpha$ and NO, whereas the production of reactive oxygen species were not altered. These results demonstrate the synergistic effects on macrophage function of RGAP in combination with IFN-$\gamma$ and suggest that the ability of IFN-$\gamma$ to prime macrophages to produce secretory molecules in response to RGAP may have implications for immunotherapy with this combination.