Gastrointestinal cancer is a great threat to human health in Japan. Conventional anti-cancer therapies including surgery, radiation, and chemotherapy are the main strategies and play important roles in curing this disease or extending the life of patients with these cancers. On the other hand, patients undergo great suffering induced by these treatments. Kampo, the Japanese traditional medicine, has been used in clinics to reduce side effects and to improve the quality of life of gastrointestinal cancer patients in Japan. In order to testify to the efficacy and safety of these Kampo medicines and to clarify the underlying mechanisms, a number of clinical and basic studies were implemented in the past several decades. These studies suggested the benefits of Kampo medicine as an adjuvant to conventional anti-cancer therapies in treating gastrointestinal cancer. Since the safety and efficacy as well as quality control of traditional medicine have long been focused worldwide, the development course of Kampo medicine may provide reference to other countries in the world.
Solasodine glycosides, such as solamargine, have been proved to be very important anti-cancer agents. In order to discover more potent cytotoxic agents and explore the preliminary structure activity relationship, a new series of solasodine glycosides 2-9 were synthesized via a transglycosylation strategy, and their cytotoxic activity against a panel of human cancer cell lines (MCF-7, KB, K562, and PC3 cells) were evaluated by MTT assays. The results indicated that compounds 2, 8, and 9 with the substitute moiety of rhamnose, 2-hydroxyethoxymethyl, and 1,3-dihydroxypropan-2-yloxy-methyl, respectively, exhibited quite strong anticancer activity. The underlying mechanism tests demonstrated that these compounds could induce apoptosis detected by DAPI staining, and Annexin V and propidium iodide binding. Cell cycle analysis indicated that the cancer cells were predominantly arrested at the G2/M phase when exposure to these compounds was examined by flow cytometry. These compounds may serve as lead candidates in the development of novel chemotherapeutics for cancer treatment.
The aim of this study was firstly to identify active molecules in herbs, that are traditionally used for the treatment of snake bite, such as Curcuma antinaia, Curcuma contravenenum, Andrographis paniculata, and Tanacetum parthenium; secondly to test similar structurally related molecules and finally to prepare and evaluate an efficient formulation against Ophiophagus hannah venom intoxification. Three labdane based compounds, including labdane dialdehyde, labdane lactone, and labdane trialdehyde and two lactones including 14-deoxy-11,12-didehydro-andrographolide and parthenolide were isolated by column chromatography and characterised. Using the isolated rat phrenic nerve-hemidiaphragm preparation, the antagonistic effect of crude extracts, isolated compounds and prepared formulations were measured in vitro on the inhibition of the neuromuscular transmission. Inhibition on muscle contraction, produced by the 5 μg/mL venom, was reversed by test agents in organ bath preparations. A labdane trialdehyde, isolated from C. contravenenum, was identified as the best antagonising agent in the low micromolar range. Tests on formulations of the most potent C. contravenenum extract showed, that the suppository with witepsol H15 was an effective medicine against O. hannah venom. This study elucidated the active compounds, accounting for the antivenin activity of traditionally used herbs and suggested the most suitable formulation, which may help to develop potent medicines for the treatment of snake bite in the future.
The discovery of somatic mutations in cancer-related genes has been applied to understand the genetic basis of cancer. Here we report somatic mutations of two tumor suppressor genes: LKB1 (exons 1, 4, and 8) and TP16 (CDKN2A) (exons 1 and 2); and two oncogenes: epidermal growth factor receptor EGFR (exons 18-21) and KRAS (exon 2) in 97 lung adenocarcinoma tissues in a cohort from the Kujukuri coast area of Chiba, Japan. In the LKB1 gene, only F354L substitutions were observed in 14 of the 97 tissue samples (14.4%). In the TP16 gene, only two deletions were observed in contrast to previous reports. On the other hand, the EGFR gene was highly mutated (38.1%) and mainly L858R substitutions occurred (23.7%) as well as insertions and deletions. In the KRAS gene, 10 substitutions at codon 12 were observed (10.3%). Co-occurrence of EGFR and KRAS somatic mutations was identified in one patient, those of EGFR and LKB1 were in three patients, and those of KRAS and LKB1 were in four patients. The lower rates of LKB1, TP16, and KRAS somatic mutations in lung adenocarcinomas are characteristic of the Kujukuri cohort as compared to Caucasians. while being infrequent in NSCLC Another review (were observed in 20.18% of lung adenocarcinoma byanalyzing the Catalog of Somatic Mutations in Cancer(COSMIC) (the W(CDKN2Aa tumor suppressor gene and has been reported to show a high rate of deletions as a major type of somatic mutation in cancerin the COSMIC database (suppressor genes, central role in tumorigenesis. EGFR phosphorylates tyrosine residues of tarincluding KRAS, to initiate multiple signaling pathwaysresulting in cell proliferation, migration, metastasis,resistance to apoptosis, and angiogenesis (molecule inhibitors of EGFR tyrosine kinase activity (TKIs) such as gefitinib and erlotinib provide a good concept for anticancer drugs. Howeversignificant variability in the EGFR
Tolerance to morphine analgesia following repeated administration disturbs the continuation of opioid therapy for severe pain. Emerging evidence suggests that the development of morphine tolerance may be antagonized by painful stimuli. To clarify the detailed mechanisms of these phenomena, we examined the effects of several pain stimuli on morphine-induced tolerance. Subcutaneous (s.c.) injection of morphine (10 mg/kg) produced an analgesic effect, which was evaluated by tail-pinch test. Morphine-induced analgesia was diminished by repeated administration of morphine (10 mg/kg, s.c.) once a day for 5 days, demonstrating the development of tolerance. Morphine analgesic tolerance was suppressed by nerve injury-induced neuropathic pain and formalin- or carrageenan-induced inflammatory pain. Tolerance to serum corticosterone elevation by morphine (10 mg/kg), which was evaluated by fluorometric assay, was also suppressed by formalin-induced inflammatory pain. Moreover, morphine analgesia induced by intracerebroventricular (10 nmol) or intrathecal (5 nmol) injection was diminished by repeated administration of morphine s.c., and this was also suppressed by carrageenan-induced inflammatory pain. These results suggest that morphine tolerance is inhibited by several pain stimuli, including neuropathic and inflammatory pain, through central mechanisms.
In the present study, quercetin (QT), morin (MR), and quercetin-3-O-glucopyranoside (QG) isolated from guava leaves were comparatively tested for antioxidant activity using DPPH, ABTS, and FRAP methods. QT was the most active among them. The free radical scavenging activity of QT was approximately four times higher than MR and two times higher than QG. The reducing power of QT was eight times higher than MR and two times higher than QG. A mixture of QT with MR or QG showed interesting combination effect. The synergistic antioxidant activity was obtained when QT was mixed with MR whereas the antagonistic effect was found when mixed with QG. The stability study of QT in liquid preparations indicated that the decomposition reaction rate of QT could be explained by a kinetic model assuming a first-order chemical reaction. The aqueous solution of QT was rapidly decomposed with t1/2 of approximately five days whereas QT entrapped in chitosan nanoparticles was five times longer. It was concluded that QT was the most active antioxidant from guava leaves. Entrapment of QT in chitosan nanoparticles could significantly enhance its stability.
A flow injection analysis (FIA) system for evaluation of the antioxidant activity of a compound capable of scavenging a hypochlorite anion (OCl–), one of the reactive oxygen species (ROS), was developed. Aminophenyl fluorescein (APF), a fluorescence indicator of ROS, was mixed manually with the test compounds and the mixed solution was injected into the FIA system. The injected solution was reacted in-line with OCl–, that was produced by using sodium dichloroisocyanurate in the presence of 0.1 M CH3CO2Na in H2O. The fluorescence intensity of fluorescein generated from non-fluorescent APF was significantly attenuated in compounds that had a scavenging effect on OCl–. The precision obtained by the FIA system was satisfactory (relative standard deviation < 5.0%) and a rapid assay within 0.5 min per sample was achieved. The proposed FIA system was used to demonstrate that reduced glutathione, dithiothreitol, and 3-methyl-1-phenyl-5-pyrazolone (edaravone) showed a significant scavenging effect on OCl–. Therefore, the proposed FIA system can be used as a screening assay for OCl–-scavenging compounds.
Oxytocin is very commonly used in clinical settings and is a nonapeptide hormone that stimulates the contraction of uterine smooth muscles. In this study the stability of extemporaneously compounded oxytocin solutions was investigated in polyolefin bags. The sterile preparations of oxytocin were compounded to the strength of 0.02 U/mL in accordance with United States Pharmacopeia (USP) <797> standards. In order to carry out the stability testing of these parenteral products, the solutions were stored under three different temperature conditions of −20°C (frozen), 2-6°C (refrigerated), and 22-25°C (room temperature). Three solutions from each temperature were withdrawn and were assessed for stability on days 0, 7, 15, 21, and 30 as per the USP guidelines. The assay of oxytocin was examined by an HPLC method at each time point. No precipitation, cloudiness or color change was observed during this study at all temperatures. The assay content by HPLC revealed that oxytocin retains greater than at least 90% of the initial concentrations for 21 days. There was no significant change in pH and absorbance values for 21 days under all the conditions of storage. Oxytocin parenteral solutions in the final concentration of 0.02 U/mL and diluted in normal saline are stable for at least 30 days under frozen and refrigerated conditions for 30 days. At the room temperature, the oxytocin solutions were stable for at least 21 days. The stability analysis results show that the shelf-life of 21 days observed in this study was far better than their recommended expiration dates.