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Affiliation |
Faculty of Agriculture Region of Applied Biochemistry and Biotechnology |
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Title |
Associate Professor |
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Related SDGs |
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NISHIKAWA Miyu
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Research Areas 【 display / non-display 】
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Life Science / Nutrition science and health science
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Life Science / Food sciences
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Life Science / Molecular biology
External Career 【 display / non-display 】
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University of Miyazaki Unit of Applied Biochemistry and Biotechnology, Division of Agriculture, Faculty of Agriculture Associate Professor
2025.4
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Toyama Prefectural University Faculty of Engineering Department of Biotechnology Assistant Professor
2019.4 - 2025.3
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Toyama Prefectural University Researcher
2013.10 - 2019.3
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Toyama Prefectural University Researcher
2011.4 - 2013.3
Professional Memberships 【 display / non-display 】
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日本フードファクター学会
2018
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日本薬学会
2017
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日本毒性学会
2015
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日本ビタミン学会
2012
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日本農芸化学会
2012
Papers 【 display / non-display 】
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Regio-specific synthesis of flavonoid glucuronides using plant UDP-glucuronosyltransferase expressed in yeast. Reviewed International journal
Mst Julia Sultana, Takuto Kurakawa, Miyu Nishikawa, Shinichi Ikushiro
Bioscience, biotechnology, and biochemistry 89 ( 7 ) 954 - 964 2025.6
Language：English Publishing type：Research paper (scientific journal)
Glucuronidation is a well-established biotransformation process that modifies the physiological and pharmacological properties of small molecules, making it a valuable tool for enhancing the chemical diversity of natural compounds in drug development. However, the chemical synthesis of glucuronides is often complex, time-consuming, and environmentally unsustainable. To overcome these challenges, plant uridine diphosphate (UDP)-glucuronosyltransferase (UGT)-mediated glucuronidation, using transformed yeast, offers a selective and efficient alternative for producing flavonoid glucuronides. This study aimed to conjugate quercetin with glucuronic acid by stably co-transforming Saccharomyces cerevisiae with plant UGTs (UGT78A11 and UGT88D7) and rat UDP-glucose-6-dehydrogenease. The UGT78A11 and UGT88D7 selectively conjugated quercetin at specific positions, producing quercetin-3-O-glucuronide and quercetin-7-O-glucuronide, respectively. The whole-cell biotransformation platform effectively leverages the regio-selectivity of UGT78A11 and UGT88D7 to convert polyhydroxy secondary metabolites into monoglucuronides with promising yields, thereby enhancing the availability and physiological potential of these glucuronides.
DOI： 10.1093/bbb/zbaf049
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Validation of a quantitation method for conjugated quercetin in human plasma. Reviewed International journal
Yui Sudaka, Takafumi Mitsui, Hiroaki Kida, Mst Julia Sultana, Miyu Nishikawa, Shinichi Ikushiro, Naoto Yamaguchi
Journal of pharmaceutical and biomedical analysis 258 116738 - 116738 2025.6
Language：English Publishing type：Research paper (scientific journal)
Since the type of glycoside affects the pharmacokinetic profile of the aglycon after oral ingestion of quercetin glycosides, clinical studies on the pharmacokinetics of quercetin glycosides are required. However, a suitable method to determine the concentrations of quercetin phase II metabolites in human plasma and urine is lacking. Therefore, we developed and validated an LC-MS method for the quantitation of conjugated quercetin using relevant reference standards, including hetero-conjugates with glucuronic acid and sulfonic acid (QC-GA/S). Quercetin hetero-conjugates extracted from rat serum were used for the method development, and reference standards were biosynthesized for the quantitation. The use of a solid-phase extraction (SPE) column in a 96 well format enabled high-throughput analysis of up to 96 tests in a day, without compromising recovery and sensitivity. The SPE column with a weak anion exchange group contributed to the high recovery of QC-GA/S. The method was then validated, and its usefulness was confirmed using clinical samples. QC-GA/S was the predominant phase II quercetin metabolite after the ingestion of quercetin glucoside or quercetin supplements. Moreover, the two peaks of QC-GA/S found in human plasma and urine were isomers of QC-7GA/4'S, which has been reported as the predominant peak in rat plasma. If QC-GA/S in plasma is responsible for a physiological activity of quercetin, it is important to determine the concentration of each QC-GA/S isomer.
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Attenuative Effect of Grifola frondosa (Maitake Mushroom) on Severe DSS-Induced Colitis in Vitamin D-Deficient Mice. Reviewed International journal
Miyu Nishikawa, Risa Miyagi, Yuki Kugimiya, Seita Chudan, Yukihiro Furusawa, Shinichi Ikushiro
Molecular nutrition & food research e70135 2025.6
Language：English Publishing type：Research paper (scientific journal)
Vitamin D deficiency, which has been a global health issue for decades, is involved in gut health and diseases. We examined the health benefits of Grifola frondosa (maitake mushroom), a potent dietary source of fungal vitamin D (D2), on DSS-induced colitis in vitamin D-deficient mice. C57BL/6J mice were fed a control diet, vitamin D3-deficient diet (DD), maitake-fortified DD, or vitamin D2-fortified DD for 6 weeks. LC-MS/MS analysis demonstrated that maitake-fed mice showed an increased 25(OH)D2 alternative to 25(OH)D3 in plasma, as well as the mice fed an equivalent dose of vitamin D2. The mRNA expression profiles of vitamin D-responsive genes, including renal Cyp24a1 and Cyp27b1, were normalized in the maitake-fed mice. Severe DSS-induced colitis observed in DD mice was attenuated in maitake-fed mice; the accumulation of immune cells in the colonic mucosa and protein expression of colonic claudin-2, a target gene of the vitamin D receptor, were comparable to that in control mice. Dietary intake of maitake was effective in improving vitamin D status and biological function, demonstrating a potential attenuative effect on severe DSS-induced colitis in vitamin D3 deficient mice, as well as equivalent doses of vitamin D2.
DOI： 10.1002/mnfr.70135
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Association between serum 25-hydroxyvitamin D concentrations and urinary vitamin D metabolite concentrations measured by the NLucVDR assay. Reviewed International journal
Takuya Kushioka, Hiroki Mano, Sayuri Matsuoka, Miyu Nishikawa, Kaori Yasuda, Shinichi Ikushiro, Toshiyuki Sakaki
The Journal of steroid biochemistry and molecular biology 247 106678 - 106678 2025.3
Language：English Publishing type：Research paper (scientific journal)
It is well known that vitamin D is essential for human health; however, many people suffer from vitamin D deficiency or insufficiency worldwide, including in Japan. Serum 25-hydroxyvitamin D (25(OH)D) concentrations are typically measured to evaluate vitamin D status. In a previous study, we demonstrated that the concentrations of vitamin D metabolites in urine, measured using the NLucVDR assay system composed of a split-type nanoluciferase and the ligand-binding domain (LBD) of the human vitamin D receptor, correlated with serum 25(OH)D concentrations measured using liquid chromatography-mass spectrometry (LC-MS) or electrochemiluminescence immunoassays (ECLIAs). However, the number of participants was limited to 23. In the present study, we investigated the relationship between urinary vitamin D metabolite concentrations measured using the NLucVDR assay and serum 25(OH)D concentrations measured using ECLIA in 292 healthy individuals aged 20-69 years. We observed a significant positive correlation between 25(OH)D concentrations and urinary vitamin D metabolite concentrations (r = 0.400, p < 0.001). Furthermore, in a multiple regression model with serum 25(OH)D concentrations as the dependent variable and urinary vitamin D metabolite concentrations, sex, age, body mass index (BMI), and vitamin D intake as independent variables, urinary vitamin D metabolite concentrations showed a significant positive association with serum 25(OH)D concentrations regardless of sex, age, BMI, and vitamin D intake. Additionally, receiver operating characteristic (ROC) curve analysis was performed to evaluate whether this multiple regression model could predict vitamin D deficiency. The area under the curve (AUC) was 0.743 and 0.708 for women and men with vitamin D deficiency (serum 25(OH)D < 20 ng/mL), respectively. Our results suggest that urinary vitamin D metabolite concentrations, measured by the NLucVDR assay, may be useful for the noninvasive predictive tool of vitamin D deficiency.
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Tea Catechins in Green Tea Inhibit the Activity of SARS-CoV-2 Main Protease via Covalent Adduction Reviewed
Yoji Kato, Sakiko Suzuki, Akari Higashiyama, Ichiro Kaneko, Mitsugu Akagawa, Miyu Nishikawa, Shinichi Ikushiro
Journal of Agricultural and Food Chemistry 2025.2
Publishing type：Research paper (scientific journal) Publisher：American Chemical Society (ACS)
Awards 【 display / non-display 】
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2023年度奨励賞
2023.6 日本ビタミン学会 疾患モデル動物を用いたビタミンDの新規生理作用メカニズムに関する研究
西川美宇
Award type：Award from Japanese society, conference, symposium, etc.
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Best Poster Award
2017.7 20th International Conference on Cytochrome P450
Miyu Nishikawa
Award type：Award from international society, conference, symposium, etc.
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優秀研究発表根岸賞
2015.7 平成27年度内外環境応答・代謝酵素研究会 CYP27B1ノックアウトマウスを用いた25-ヒドロキシビタミンD3 の生理作用の検討,
西川美宇
Award type：Award from Japanese society, conference, symposium, etc.
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生理学・生化学分科会奨励賞
2010.9 第150回日本獣医学会学術集会 妊娠期におけるビスフェノールＡ投与による胎仔影響メカニズムの解明,
西川美宇
Award type：Award from Japanese society, conference, symposium, etc.
Grant-in-Aid for Scientific Research 【 display / non-display 】
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iPS細胞由来腸上皮の異物代謝応答から紐解くポリフェノールの機能発現メカニズム
Grant number：25K09020 2025.04 - 2028.03
独立行政法人日本学術振興会 科学研究費基金 基盤研究(C)
西川美宇
Authorship：Principal investigator
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体内循環特性に基づくポリフェノール機能発現メカニズムの解明
Grant number：24K01705 2024.04 - 2027.03
日本学術振興会 科学研究費基金 基盤研究(B)
生城 真一, 西川 美宇
Authorship：Coinvestigator(s)
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Hepatoprotective effect of 25-hydroxyvitamin D3 : Development of 25-hydroxtvitamin D into a new nutrition strategy
Grant number：22K11756 2022.04 - 2025.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C) Grant-in-Aid for Scientific Research (C)
Authorship：Principal investigator
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腸内細菌叢が関与する食品中機能性成分の抱合代謝物動態の総合的理解
Grant number：21H02143 2021.04 - 2024.03
日本学術振興会 科学研究費助成事業 基盤研究(B) 基盤研究(B)
生城 真一, 栗原 新, 西川 美宇
Authorship：Coinvestigator(s)
食品中の機能性成分であるフラボノイドなどはグルクロン酸や硫酸基が付加された抱合代謝物として生体内に留まり、一部は脱抱合過程を通して活性体（アグリコン）に変換される。従って、体内における抱合代謝物への変換、輸送及び排泄過程がフラボノイドの生理機能発現を規定する。近年では宿主腸内細菌叢における脱抱合による再吸収過程を通して代謝物の体内動態に関与する可能性が示唆される。本申請では、（課題１）生体に取り込まれた機能性成分の代謝物を同定するために、異物代謝酵素発現酵母を用いた代謝物の網羅的な合成プラットフォームを確立する。さらに、課題１で得られた代謝物標準品を用いて、（課題２）腸内常在細菌優勢種における脱抱合能評価により機能性成分動態に対する腸肝循環の寄与を明らかにすることにより、生体における腸内細菌叢が関与する食品中機能性成分の抱合代謝物動態の総合的理解を通して食品中の機能性成分の真の作用メカニズム解明を目指した。ケルセチンのヘテロ抱合体合成においては、ヒト由来異物代謝酵素（UDP-グルクロン酸転移酵素および硫酸転移酵素）発現酵母株を用いた。出発基質としてグルクロン酸抱合あるいは硫酸抱合化ケルセチンを異なる抱合酵素を発現する酵母菌体に添加し、最適条件下において抱合変換を行った。また、メチル化ケルセチンであるイソラムネチンのヘテロ抱合体についても同様に合成した。以下に示すように４種のケルセチンヘテロ抱合体および３種のイソラムネチンヘテロ抱合体を調製した。
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Elucidation of vitamin D actions using genetically modified rats and application of vitamin D analogs to medical drugs
Grant number：19H02889 2019.04 - 2022.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B) Grant-in-Aid for Scientific Research (B)
SAKAKI TOSHIYUKI
Authorship：Coinvestigator(s)
Rats expressing mutant VDR (H301Q) or VDR (R270L) / (H301Q) were prepared by the genome editing method, and their physiological properties were compared with existing mutant VDR (R270L) and VDR gene-deficient (VDR-KO) rats. As a result of detailed analysis of the effects of vitamin D and vitamin D receptors on bone formation, hair follicle formation, etc., it was clarified that ligand-unbound VDR is required for hair follicle formation. In addition, among the newly synthesized vitamin D derivatives, we have found several compounds that show a higher therapeutic effect on psoriasis than existing vitamin D derivatives. Furthermore, we showed the effectiveness of gene therapy using a VDR-expressing adenovirus vector for alopecia in VDR-KO rats.
Committee Memberships 【 display / non-display 】
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日本ビタミン学会 次世代ミーティング運営委員
2025.6
Committee type：学協会
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日本ビタミン学会 幹事
2025.6
Committee type：学協会
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日本フードファクター学会 評議員
2021.11
Committee type：学協会
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日本生化学会北陸支部 幹事
2020.6 - 2022.5
Committee type：学協会