Bioactive compounds from plant (phytochemicals) play an important role as seed compounds for prevention and treatment of many diseases. Recently, the author isolated a novel topoisomerase II inhibitor named erypoegin K, an isoflavone from Erythrina poeppigiana, which showed enantio-selective potent apoptosis-inducing activity towards various types of cancer cells. This review mainly describes studies on erypoegin K. It also includes other phytochemicals with apoptosis-inducing and anti-inflammatory activities. This review is useful for researchers developing new anticancer and anti-inflammatory drugs.
Vitamin E (α-tocopherol) is the most important lipid-soluble antioxidant in humans. The author identified a soluble protein that specifically binds α-tocopherol and named it α-tocopherol transfer protein (α-TTP). He found that α-TTP is a major determinant of vitamin E levels in the body and that its mutation causes severe vitamin E deficiency. α-TTP catalyzes intracellular vectorial transport of vitamin E by exchange with phosphatidylinositol phosphates (PIPs), and this mechanism may be applicable to other intracellular lipid transfer proteins.
Naldemedine (Nal) is widely used as a therapeutic drug against opioid-induced constipation (OIC). However, patients in phase III trials are limited to those with good performance status (PS). This study aimed to evaluate Nal efficacy in patients with poor PS. In conclusion, Nal showed similar effectiveness in patients with poor PS as that in those with good PS. Authors findings could be helpful in the treatment of patients with OIC.
One of the important characteristics of natural medicines, including crude drugs and Kampo prescriptions, is that they contain many constituents, and their therapeutic effects result from the total effects of the constituents. The author reviewed various synergistic effects and interactions among the constituents of natural medicines experienced in his researches. This review will provide an opportunity to have a glimpse into the scientific basis of the effectiveness of natural medicines as multicomponent medicines.
Discovery of natural products that possess novel chemical structures and pharmaceutical activities increases opportunities of drug development. In this post genomic era, it is cleared that fungi have a huge number of silent biosynthetic gene clusters and they are recognized as an attractive source for natural product discovery. The author developed methods to activate fungal silent biosynthetic gene clusters by using epigenetic modifiers and plant hormones and demonstrated their advantage to get a variety of new natural products.
There are still many diseases that have no therapeutic approach even today. Against this background, we have duty to think the future of the field of pharmacy. This paper describes the importance of sharing awareness of problems among different specialists such scientist and pharmacist. Furthermore, this paper also introduced the result of the symposium which consist of enzyme engineering, total synthesis and medicinal chemistry in the 141st annual meeting of the Pharmaceutical Society of Japan.
This research paper improves the TDBPP and BDBPP analysis methods of organic phosphorus flame retardants regulated by the Act on the Control of Household Products Containing Harmful Substances Japan. The authors proposed a GC-MS analysis method instead of the GC-FPD method. The new method is performed safely without using harmful reagents in the pretreatment. Furthermore, the high-sensitive analysis is realized by surrogate correction.
The author has an interest in unique chemical and physical properties of fullerene (C60) and fullerene derivatives, and has studied bio-active fullerene derivatives to develop novel lead compounds for drug discovery. He showed that anionic fullerene derivatives possess anti-oxidant activities, di-cationic fullerene derivatives exhibited antiproliferative activities against various cancer cell lines including drug-resistant cells, and proline-type fullerene derivatives showed anti-virus activities. The process of the studies is also written in this report.
The presence or absence of drug crystals in a matrix-type transdermal patch is generally confirmed by visual or optical observation of the exposed adhesive surface. This method consumes one patch per observation. The present study investigated the feasibility of crystal detection in a patch, enclosed in an unopened outer bag, by laboratory X-ray diffraction. The results showed that a laboratory-level high-resolution X-ray diffractometer can be used to detect unintentionally crystallized spots, and examine the crystalline state including polymorphism.
Due to aging society of Japan, ophthalmic research is becoming more importance in not only doctor and nurse but pharmacist. This symposium (review) shows the state of the art in “Age-related changes in eye function and preventive ways”, and update ophthalmic studies including senescence, antiaging, immune privilege and drug delivery system. Many members will be interested in the ophthalmic research field when they read this review, and the information will help to improve the “Quality of Vision” in aging society.
Three subtypes of peroxisome proliferator-activated receptors (PPARα, PPARγ, and PPARβ/δ) are attracting much attention as molecular targets of drugs to treat various metabolic diseases including dyslipidemia, type 2 diabetes, and non-alcoholic fatty liver disease; however, the structural information regarding their ligand binding pockets has been lacking, especially in PPARα. Kamata and Ishii give an overview of their recent success in obtaining 34 novel PPARα-ligand structures that supplement 21 previously PDB-deposited structures using their sophisticated crystallization techniques.
Authors analyzed the residual solvents by headspace (HS)-GC-MS in 29 products selected from among commercial supplements that are deeply colored or contain coating agents and extract. As a result, benzene (class 1) was detected in black-colored supplements. As raw materials used for the manufacture of the black-colored supplements from which benzene was detected commonly included activated carbon. In their analysis, benzene was detected at high concentrations in activated carbon made from hemp and bamboo for use as food additives.
Pharmacists are exposed to the drug when dispensing powder drug. The authors clarified the current status with scientific measurements. The pharmacists were exposed to 0.17 µg/d (median) of drug ingredients just in the dispensing room. Furthermore, dispensing drug powder increased the exposure to a maximum of 0.4–36 µg per one prescription. Although there are concerns about the health hazards of pharmacists due to exposure to drug dust, they found that wearing medical mask removed more than 90% of drug ingredient.
Organic compounds isolated from natural resources are called “natural products” and are important seed compounds for medicinal chemistry. Total synthesis of natural products is basic research for drug development by structure determination, including absolute stereochemistry and investigation of their chemical and physical properties. Many alkaloids show strong biological activities among the natural products and have been recognized as a drug or a drug candidate. Here, total syntheses of polycyclic natural products, Kopsia alkaloids, manzamine alkaloids, are discussed.
The authors retrospectively investigated the potential DDIs among three or more drugs that involve the same CYP molecular species in metabolic process in outpatients’ setting. This study found out that the more than half of the patients who took six or more drugs had potential DDIs among three or more drugs, and CYP3A4-related drugs are especially important. These findings would be useful for avoidance or early detection of adverse drug reactions caused by DDIs among three or more drugs.
MTF-1 is a transcription factor activated in response to an increase in concentration of intracellular free zinc. In this article, MTF-1 is reviewed from its discovery to unique characteristics as an intracellular zinc sensor, mainly based on the author’s research results. It is indicated that clarification of the zinc signaling system mediated by MTF-1, together with the analysis of the genes under its control, is useful for unraveling novel biological roles of essential zinc.
This study investigated the effects of fenofibrate and bezafibrate on risk of diabetic retinopathy (DR) in Japanese working age patients with type 2 diabetes and dyslipidemia using electronic medical records. Although these fibrates did not affect development of DR, poor control of hemoglobin A1c (HbA1c) and low-density lipoprotein cholesterol (LDL-C) within the follow-up period increased the risk of DR. Thus, controlling HbA1c and LDL-C levels under coexistence type 2 diabetes and dyslipidemia is more important than the selection of fibrate.
The author introduced three methods to characterize the blood-brain barrier (BBB) transport function. It was shown that the BBB plays an important role in protecting the brain by transporting small molecules such as neurotransmitters, uremic toxins and xenobiotics together with proteins. Significant species differences were shown in the expression amounts of various BBB transporter proteins. Moreover, in vivo BBB efflux transport activity was predicted from in vitro study and transporter protein concentration.
The authors report on pharmacists’ work that is unique to surgical departments. Pharmacists prepare drug solutions utilizing anesthesia recording systems, which they were involved in developing. Anesthesiologists request pharmacists to prepare drug solutions after estimating the degree of postoperative pain in the surgical field during surgery. Pharmacists then prepare specific solutions after consultation and discussion with anesthesiologists. In this study, the authors investigated the evaluation of pharmacists’ practices by anesthesiologists and found that pharmacists received favorable evaluations.
Distigmine is a cholinesterase inhibitor, which is used in Japan for the treatment for underactive bladder. Although the effectiveness of distigmine for underactive bladder treatment has been confirmed by many clinical reports, the pharmacological effects of distigmine on urinary bladder (UB) motility have not been well studied. In this review, the authors discuss the long-lasting potentiating effect of distigmine on guinea pig UB motility and the mechanism of these effects in guinea pig UB smooth muscle and recombinant human acetylcholinesterase.