Circadian disruption and human health.

Circadian disruption is pervasive and can occur at multiple organizational levels, contributing to poor health outcomes at individual and population levels. Evidence points to a bidirectional relationship, in that circadian disruption increases disease severity and many diseases can disrupt circadian rhythms. Importantly, circadian disruption can increase the risk for the expression and development of neurologic, psychiatric, cardiometabolic, and immune disorders. Thus, harnessing the rich findings from preclinical and translational research in circadian biology to enhance health via circadian-based approaches represents a unique opportunity for personalized/precision medicine and overall societal well-being. In this Review, we discuss the implications of circadian disruption for human health using a bench-to-bedside approach. Evidence from preclinical and translational science is applied to a clinical and population-based approach. Given the broad implications of circadian regulation for human health, this Review focuses its discussion on selected examples in neurologic, psychiatric, metabolic, cardiovascular, allergic, and immunologic disorders that highlight the interrelatedness between circadian disruption and human disease and the potential of circadian-based interventions, such as bright light therapy and exogenous melatonin, as well as chronotherapy to improve and/or modify disease outcomes.

Asian ginseng enhances the anti-proliferative effect of 5-fluorouracil on human colorectal cancer: comparison between white and red ginseng.

Previous studies showed that Asian ginseng, Panax ginseng C.A. Meyer, may have anti-cancer properties. However, there is limited data exploring the use of Asian ginseng as an adjuvant to chemotherapy, and minimal mechanistic studies related to their possible synergistic activities. In this study, the content of 8 ginsenosides, Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1 and Rg3, in the extracts of white ginseng (WG) and red ginseng (RG) were determined by HPLC. Using HCT-116 human colorectal cancer cells, we compared the efficacy of WG and RG. We evaluated the synergy between ginseng and 5-fluorouracil (5-FU), and explored the mechanism of their anti-proliferative effects. As single extract, WG or RG used at concentrations of 0.1, 0.2 and 0.3 mg/mL, inhibited HCT-116 cell proliferation in a concentration-related manner. WG at 0.2 mg/mL did not show obvious synergy with 5-FU co-treatment, while RG at 0.2 and 0.3 mg/mL significantly enhanced the anti-proliferative effects of 5-FU at concentrations of 10, 50 and 100 microM (P < 0.05). Using flow cytometric assay, RG 0.3 mg/mL did not affect cancer cell apoptotic induction activity. However, the RG induced cell cycle arrest in the G1 phase, while 5-FU arrested the cell in the S phase. Different ginsenoside profiles are responsible for the observed differences in pharmacological effects. The effects of 8 ginsenosides on HCT-116 cells were assayed. Rd and Rg3 showed positive anti-proliferative effect. Our data suggested a potential for RG as an adjuvant therapy in the treatment of colorectal cancer, via a synergistic action.

The mitochondrial pathway is involved in American ginseng-induced apoptosis of SW-480 colon cancer cells.

Numerous effective anticancer drugs have been developed from botanical sources, and there remains a significant untapped resource in herbal medicines. In this study, we evaluated the chemical composition of extracts from American ginseng after steaming, the antiproliferative effects of the ginsenosides in the extracts on SW-480 human colorectal cancer cells, and their apoptotic mechanisms. American ginseng roots were steamed at 120 degrees C for 2 or 4 h. Representative ginsenosides in the unsteamed and steamed extracts were determined using HPLC. The antiproliferative effects of the ginsenosides Rb1, Rg3 and Rh2 on SW-480 cells were determined by the MTS method. The effect of extract steamed for 4 h on apoptosis of SW-480 cell was assayed by flow cytometry after staining with annexin V/PI. The expression of 84 apoptotic-related genes, including TNF, mitochondria and p53 pathways, was determined using real-time quantitative PCR array analysis. The mitochondrial membrane potential (Deltapsim) was analyzed after staining with FC-1. Steaming of American ginseng increased Rg3 and Rh2 content and antiproliferative activity significantly. The quantitative PCR array data demonstrated that multiple genes in mitochondrial pathway are involved in American ginseng-induced apoptosis of SW-480 cells and the expression profiling was validated by the cellular functional assay. The mitochondrial pathway may play a key role in American ginseng-mediated cancer cell apoptosis.