{"title":"[The Potential Analysis of Flavoring Agents as Novel Functional Foods].","authors":"Takuya Yamashita, Kazuya Nagano","doi":"10.1248/yakushi.24-00173-1","DOIUrl":"https://doi.org/10.1248/yakushi.24-00173-1","url":null,"abstract":"<p><p>Functional foods have attracted increasing attention. To prevent diseases using functional foods, various unhealthy conditions must be addressed, such as blood lipids, blood sugar, and blood pressure. However, there are insufficient functional ingredients available to address these unhealthy conditions. For example, five main ingredients (such as γ-aminobutyric acid) currently predominate in foods with functional claims, and account for approximately 38.2% of the total registered products in Japan. These data suggest that some functional and safe ingredients are widely used. From this perspective, enhancing the lineup of functional ingredients is necessary to address unhealthy conditions and develop various functional foods in the future. Flavoring agents are attractive ingredients. However, studies on flavoring agents have focused only on psychological functions, such as relaxation. In this study, we discuss the potential use of flavoring agents as functional ingredients.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 1","pages":"17-21"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Current Situation and Challenges of Regulation and Analytical Methods for Residual Pesticides, Veterinary Drugs and Mycotoxins in Foods].","authors":"Takaaki Taguchi, Tomoaki Tsutsumi","doi":"10.1248/yakushi.24-00164-F","DOIUrl":"https://doi.org/10.1248/yakushi.24-00164-F","url":null,"abstract":"","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 2","pages":"93-94"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Disease Research and Drug Development Pioneered by Female Researchers with a Focus on the Liver].","authors":"Yukiko Ueyama-Toba, Kahori Shimizu","doi":"10.1248/yakushi.24-00177-F","DOIUrl":"https://doi.org/10.1248/yakushi.24-00177-F","url":null,"abstract":"","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 3","pages":"169-170"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Application of Human Liver Organoids for Pharmaceutical Research].","authors":"Yukiko Ueyama-Toba, Yanran Tong, Hiroyuki Mizuguchi","doi":"10.1248/yakushi.24-00177-4","DOIUrl":"https://doi.org/10.1248/yakushi.24-00177-4","url":null,"abstract":"<p><p>Human liver organoids are expected to be a hepatocyte source for preclinical in vitro studies of drug metabolism and disposition. Although these organoids show long-term proliferation, their hepatic functions remain low. Therefore, it is necessary to enhance the hepatic functions of primary human hepatocyte (PHH)-derived organoids. Here, we propose a novel method for two dimensional (2D)-cultured hepatic differentiation from PHH-derived organoids. PHH-derived organoids were established from cryopreserved PHHs. When cultured under a 2D condition, the single cells from PHH-derived organoids were seeded on collagen type I-coated plates. Then, optimal conditions for hepatic differentiation were screened using several compounds, cytokines and growth factors. Based on the results of the screening, we determined the 2D-cultured hepatic differentiation method from PHH-derived organoids. Hepatic gene expressions in PHH-derived organoids-derived hepatocytes (Org-HEPs) were greatly increased, compared to those in PHH-derived organoids. An RNA-seq analysis showed that gene expressions related to pharmacokinetics were upregulated in Org-HEPs compared to PHH-derived organoids. The metabolic activities of CYP1A2, CYP2C8, CYP2E1 and CYP3A4 were at levels comparable to those in PHHs. We also treated Org-HEPs and PHHs with hepatotoxic drugs, such as acetaminophen, troglitazone, amiodarone and clozapine. The cell viability of Org-HEPs was almost the same as that of PHHs. These results suggested that PHH-derived organoids could be differentiated into highly functional hepatocytes in 2D culture, and Org-HEPs could be used for hepatotoxicity tests. Thus, Org-HEPs will be useful for pharmaceutical research.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 3","pages":"189-194"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Roles of Trophoblast Differentiation, Cell Fusion, and Microvilli Formation in Placentation and Prospects for a Model for Their Assessment].","authors":"Mikihiro Yoshie, Atsuya Tsuru, Kazuhiro Tamura","doi":"10.1248/yakushi.24-00174-2","DOIUrl":"https://doi.org/10.1248/yakushi.24-00174-2","url":null,"abstract":"<p><p>The placenta, which acts as an interface between fetal and maternal circulations, is an indispensable organ for fetal growth in mammalian pregnancy. It mediates the transportation of nutrients, the exchange of gases such as oxygen and carbon dioxide, and the excretion of waste products between the fetus and mother. The surface of placental villi is covered by two layers of mononuclear undifferentiated cytotrophoblasts (CT) and multinucleated syncytiotrophoblasts (ST). The formation of the multinucleated ST layer via fusion of CT is referred to as syncytialization, which is a well-characterized morphological sign of terminal differentiation. STs function not only as the placental barrier to separate maternal blood from fetal tissue but also as the main source of human chorionic gonadotropin (hCG) and progesterone (P4) during pregnancy. The significance of appropriate differentiation and fusion of CTs to form STs is demonstrated by the finding that disturbance of these processes is linked to the pathogenesis of pregnancy-associated complications such as hypertensive disorders of pregnancy (HDP) and fetal growth restriction (FGR). In this review, we focused on trophoblast differentiation, cell fusion and microvilli formation, and showed the role of short-chain fatty acid butyrate and progesterone receptor membrane component 1 (PGRMC1) in these processes. Furthermore, we described the evaluation of placental function and its prospects utilizing a quantitative trophoblast cell fusion system and microfluidic device.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 1","pages":"49-52"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Curative Treatment for COPD Based on Differentiation Induction by Synthetic Retinoid Am80 and Development of Inhalation Powder].","authors":"Tomomi Akita","doi":"10.1248/yakushi.24-00139","DOIUrl":"https://doi.org/10.1248/yakushi.24-00139","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis and emphysema, and current drug treatments is limited to symptomatic therapy. Thus, there is an urgent need for development of new treatments to repair alveolar destruction. To regenerate the destroyed alveoli, we focused on the differentiation of alveolar epithelial progenitor cells into type I or type II alveolar epithelial cells that constitute the alveoli. Our concept of alveolar regeneration therapy is based on developing a drug delivery system (DDS) and dry powder inhalation that can efficiently deliver new alveolar regeneration drugs, which were discovered using human alveolar epithelial progenitor cells, to stem cells present on the surface of the alveoli of COPD patients, thereby inducing alveolar regeneration. This review article summarizes our data on the discovery of the synthetic retinoid Am80 as a candidate drug for alveolar regeneration, the construction of a DDS that utilizes a biological mechanism that enhances its effect on alveolar regeneration, and the formulation design of a dry powder inhalation.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 1","pages":"1-6"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Molecular Mechanisms by Which Polyunsaturated Fatty Acids Suppress the Pathogenesis and Progression of NAFLD].","authors":"Misa Ando, Hyeon-Cheol Lee-Okada, Takehiko Yokomizo","doi":"10.1248/yakushi.24-00177-2","DOIUrl":"https://doi.org/10.1248/yakushi.24-00177-2","url":null,"abstract":"<p><p>In recent years, the number of people suffering from lifestyle diseases such as hyperlipidemia and fatty liver disease has increased rapidly due to westernization of dietary patterns. Among fatty liver diseases, those that are not caused by alcohol are referred to as nonalcoholic fatty liver disease (NAFLD). Some NAFLD can progress to nonalcoholic steatohepatitis (NASH), and further progression of NAFLD can lead to cirrhosis and liver cancer. Although numerous studies have demonstrated the efficacy of dietary polyunsaturated fatty acids (PUFAs), particularly omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), against NAFLD, the detailed mechanisms by which these PUFAs exert their protective effects on the pathogenesis and progression of NAFLD are not well understood. Recent studies using knockout mouse models and genome-wide association studies have suggested a potential role for the enzymes responsible for the biosynthesis of PUFAs (FADS1, FADS2, ELOVL2, and ELOVL5) and their incorporation into phospholipids (LPCAT3/MBOAT5/LPLAT12 and LPIAT1/MBOAT7/LPLAT11) in the development of NAFLD. In this review, we summarize recent findings on the association of NAFLD and PUFAs with a focus on PUFA biosynthetic and metabolic enzymes to discuss the potential role of PUFAs in the prevention of NAFLD.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 3","pages":"177-182"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kahori Shimizu, Hideo Shindou, Koji Tomita, Toru Nishinaka
{"title":"[Approaches to the Treatment of Lifestyle-related Diseases Through the Regulation of Phospholipid Biosynthesis in the Liver].","authors":"Kahori Shimizu, Hideo Shindou, Koji Tomita, Toru Nishinaka","doi":"10.1248/yakushi.24-00177-1","DOIUrl":"https://doi.org/10.1248/yakushi.24-00177-1","url":null,"abstract":"<p><p>The incidence of type 2 diabetes mellitus (T2DM), a major lifestyle-related disease, is increasing worldwide. T2DM, which accounts for approximately 90-95% of all diabetes mellitus cases, is caused by deficient insulin secretion, tissue insulin resistance, or both. Many therapeutic drugs for T2DM have been developed that target the pancreas, which secretes insulin. The liver is the central organ for glucose and lipid metabolism, and failure of hepatic regulatory mechanisms leads to hyperglycemia, insulin resistance, and lipid accumulation. Here, we focused on the liver as a novel therapeutic target for T2DM. The fatty acid composition of phospholipids, a major component of biological membranes, has received considerable research attention owing to their involvement in T2DM onset and progression. Fatty acids in phospholipids are cleaved by phospholipase A to form lysophospholipids, which are subsequently remodeled back into phospholipids by lysophospholipid acyltransferases (LPLATs). LPLATs play an important role in lipid metabolism and homeostasis by regulating the abundance of various phospholipid species in multiple cell and tissue types. We investigated whether overexpression of LPLAT10, also called LPCAT4 and LPEAT2, in the liver could improve abnormalities in glucose metabolism and help treat T2DM. For overexpression, we generated an LPLAT10-expressing adenovirus (Ad) vector using an improved Ad vector named Ad-E4-122aT, which exhibited higher and longer-term transgene expression and lower hepatotoxicity than conventional Ad vectors. In this article, we review the current findings that changes in hepatic phospholipid species due to liver-specific LPLAT10 overexpression affect the pancreas and suppress postprandial hyperglycemia by increasing postprandial insulin secretion.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 3","pages":"171-176"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[The Roles and Operations of Registered Conformity Assessment Body].","authors":"Takayuki Asakura","doi":"10.1248/yakushi.24-00164-3","DOIUrl":"https://doi.org/10.1248/yakushi.24-00164-3","url":null,"abstract":"<p><p>As of August 2023, 99 organizations were registered as conformity assessment bodies by the Ministry of Health, Labour, and Welfare in accordance with Article 33 of the Food Sanitation Act. These registered organizations are authorized to conduct inspections of imported food as well as domestic expropriation inspections. In recent years, we have actively participated in a project to develop new test methods, aiming to enhance our contribution as a registered testing organization and to maintain food hygiene by widely applying these developed methods. There is a need to develop new test methods for pesticides and veterinary medicines used in Japan, as well as for several drugs used internationally. Previously, gas chromatography and high-performance liquid chromatography were the standard methods, and only parent compounds were analyzed. Recently, the demand for test methods applicable not only to agricultural products but also to livestock and marine foods has increased, necessitating the analysis of metabolites in addition to parent compounds. Although developing analytical methods to detect certain metabolites has been challenging, advancements in the variety of separation and pretreatment columns, along with the widespread use of LC-MS/MS and GC-MS/MS techniques, have enabled the development of test methods for many compounds. In this study, we introduce a method to solve the challenges and problems associated with test method development.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 2","pages":"105-108"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Anti-skin Aging Effects of Kale-derived Exosome-like Nanoparticles].","authors":"Shigeru Katayama","doi":"10.1248/yakushi.24-00173-3","DOIUrl":"https://doi.org/10.1248/yakushi.24-00173-3","url":null,"abstract":"<p><p>In an aging society, there is a growing interest in functional foods that offer anti-aging benefits. Food-derived bioactive compounds such as carotenoids and polyphenols can enhance skin elasticity and delay aging. However, the mechanisms by which these orally ingested compounds directly impact the skin are not fully understood. Recent studies on exosomes have suggested significant physiological functions, including their potential for intercellular communication. Similar to mammalian exosomes, plant-derived exosomes are known for their functional roles, including cross-kingdom communication, and their ability to target specific organs in animal models as delivery vehicles. The authors have been investigating the anti-aging effects of kale and have previously reported its benefits on cognitive function and skin aging in mouse models. Long-term oral administration of glucoraphanin-enriched kale suppresses the senescence symptoms in skin and hair and increases type I collagen and antioxidant enzyme expression in skin tissues, indicating its role in promoting skin health. Exosome-like nanoparticles (ELNs) from glucoraphanin-enriched kale appear to modulate the expression of extracellular matrix-related genes. Kale-derived ELNs exhibit great potential for ameliorating skin aging, suggesting their ability to promote skin health through targeted cellular mechanisms and supporting their use as an active natural compound in nutraceuticals and functional beverages.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"145 1","pages":"29-33"},"PeriodicalIF":0.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}