Biological & pharmaceutical bulletin
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Panax Notoginseng Saponins (PNS) have been well known to have anti-tumor activity and enhance cytotoxicity of some cancer chemotherapy agents, but the mechanisms underlying these effects are still unknown. This study investigates the effect of PNS on cytotoxicity of cisplatin and the relationship between this effect and the modulation of gap junctions (GJ) function by PNS in a transfected cell line. The cytotoxicity of cisplatin (0.25-1 µg/mL) was increased in the presence of GJ. ⋯ PNS (50-200 µg/mL) significantly enhanced cisplatin cytotoxicity, but this effect required functional gap junctions between the cells. Exposure of the cells to PNS (50-200 µg/mL) for 4 h leads to a significant enhance in dye coupling of GJ in a dose-dependent manner. These results suggest that PNS increases the cytotoxicity of cisplatin through enhancement of GJ activity.
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Capecitabine, an oral prodrug of 5-fluorouracil (5-FU), is a promising treatment for colorectal, breast and gastric cancers, but often causes hand-foot syndrome (HFS), the most common dose-limiting toxicity. The current study was conducted to investigate the relationship between HFS and efficacy of capecitabine in 98 patients with metastatic breast cancer. Possible associations between HFS and efficacy endpoints, including time-to-treatment failure (TTF), tumor response in metastatic lesions and changes in tumor markers, were investigated retrospectively using electronic medical records. ⋯ Furthermore, prevention of increases in tumor marker levels (carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3) and National Cancer Center-Stomach-439 (NCC-ST439)) was evident in patients with HFS. This study clearly showed a significant correlation between HFS and some efficacy markers of capecitabine therapy in patients with metastatic breast cancer, and suggests that early dose adjustment based on severity of HFS might improve efficacy. Studies are needed to explore predictive biomarkers for HFS/efficacy, so that capecitabine therapy can be further tailored to patient response.
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Rhubarb is one of the most well-known herbal medicines that constitute daiokanzoto (DKT), which is clinically effective for constipation. Sennoside A is transformed into an active metabolite, rheinanthrone, by intestinal bacteria. Sennoside A in rhubarb showed significantly accelerated metabolic activity in intestinal bacteria in comparison with sennoside A alone. ⋯ The purgative activity of sennoside A was significantly accelerated when RG or rhein was concomitantly given with sennoside A in a dose-dependent manner. These results suggest that anthraquinones contribute to the purgative action of sennoside A in rhubarb. Therefore, it is assumed that the influence of anthraquinones on the fate of rheinanthrone transformed from sennoside A may promote the purgative action of sennoside A.
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Hemorrhagic shock (HS) is a common condition and leading cause of death in trauma patients universally. Severe inflammatory responses during HS finally lead to multiple-organ failure. Hydrogen sulphide (H₂S) is increasingly recognized as an important signaling molecule with various protective effects. ⋯ NaHS also inhibited the nuclear factor κB inhibitor kinase (IKK)/nuclear factor κB inhibitor (IκB)/nuclear factor κB (NF-κB) signaling pathway. The results suggest that NaHS exerts cardioprotective effects against HS. The protective effects of NaHS may occur via down-regulation of the IKK/IκB/NF-κB signaling pathway.
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In India, Azadirachta indica is typically known as 'neem tree' and its leaves has long been used in the ayurvedic medical tradition as a treatment for diabetes mellitus. In-depth chromatographic investigation on chloroform extract resulted in identification of one new tetranortriterpenoid. Structural elucidation was established on the basis of spectral data as 24,25,26,27-tetranor-apotirucalla-(apoeupha)-1α-senecioyloxy-3α,7α-dihydroxy-14,20,22-trien-21,23-epoxy named by us as meliacinolin (1). ⋯ As a result we found that blood glucose level, serum biochemical parameters, hepatic enzymes, thiobarbituric acid reactive substances, and insulin level were restored in streptozotocin (STZ)-diabetic mice to normal levels with 1. Meliacinolin inhibited α-glucosidase and α-amylase activities. We conclude that meliacinolin can efficiently inhibit insulin resistance, improvement of renal function, lipid abnormalities, and oxidative stress, indicating that its therapeutic properties may be due to the interaction of meliacinolin with multiple targets involved in diabetes pathogenesis. α-Glucosidase and α-amylase inhibitors offer an effective strategy to lower the levels of post prandial hyperglycemia prevents the digestion of carbohydrates.