Effects of gut microflora on pharmacokinetics of hesperidin: a study on non-antibiotic and pseudo-germ-free rats.

Jin, Ming Ji,Kim, Unyong,Kim, In Sook,Kim, Yuri,Kim, Dong-Hyun,Han, Sang Beom,Kim, Dong-Hyun,Kwon, Oh-Seung,Yoo, Hye Hyun Taylor Francis 2010 Journal of toxicology and environmental health. Pa Vol.73 No.21

<P>Hesperidin is a biologically active flavanone glycoside occurring abundantly in citrus fruits. In the present study, effects of intestinal microflora on pharmacokinetics of hesperidin were investigated using a pseudo-germ-free rat model treated with antibiotics. After administration of hesperidin to rats, hesperetin, hesperetin glucuronides, and metabolites postulated to be eriodictyol, hemoeriodictyol, and their glucuronides were detected in urine while hesperetin glucuronide was predominantly found in plasma. The plasma concentration-time profile of hesperetin was compared between non-antibiotic-exposed and pseudo-germ-free rats administered this compound. The maximal concentration (C(max)) values of hesperetin in non-antibiotic-exposed and pseudo-germ-free rats were 0.58 and 0.20 관g/ml, respectively, and area under the curve (AUC) values were 6.3 and 2.8 관g-h/ml, respectively. Thus, systemic exposure as evidenced by AUC and C(max) was significantly higher in normal compared to pseudo-germ-free rats. Fecal 관-glucosidase activities of non-antibiotic-exposed and pseudo-germ-free rats were 0.21 and 0.11 nmol/min/mg, while fecal 관-rhamnosidase activities were 0.37 and 0.12 nmol/min/mg, respectively. The rate of hesperidin transformation to hesperetin was 6.9 and 2.9 nmol/min/g in fecal samples in non-antibiotic-exposed and pseudo-germ-free rats, respectively. Taken together, these results showed that pharmacokinetic differences between non-antibiotic-exposed and pseudo-germ-free rats may be attributed to differing hesperidin uptake, as well as alterations in metabolic activities of intestinal flora.</P>

Pharmacokinetic Profile of Eight Phenolic Compounds and Their Conjugated Metabolites after Oral Administration of <i>Rhus verniciflua</i> Extracts in Rats

Jin, Ming Ji,Kim, In Sook,Park, Jong Suk,Dong, Mi-Sook,Na, Chun-Soo,Yoo, Hye Hyun American Chemical Society 2015 Journal of agricultural and food chemistry Vol.63 No.22

<P><I>Rhus verniciflua</I> (<I>Toxicodendron vernicifluum</I>) is a medicinal tree popularly used in Asian countries such as China, Japan, and Korea as a food additive or herbal medicine because of its beneficial effects. <I>R. verniciflua</I> extract (RVE) contains diverse phenolic compounds, such as flavonoids, as its major biological active constituents. In this study, the pharmacokinetic profiles of eight phenolic compounds were investigated following oral administration of RVE to rats. The eight phenolic compounds were 2,4-dihydroxybenzoic acid, 3,4-dihydroxybenzoic acid, fisetin, fustin, butin, sulfuretin, taxifolin, and garbanzol. The plasma concentrations of the eight compounds were determined by using a liquid chromatography–triple-quadrupole mass spectrometer before and after treatment with β-glucuronidase. When 1.5 g/kg RVE was administered, the eight compounds were all detected in plasma, mainly as conjugated forms. These pharmacokinetic data would be useful for understanding the pharmacological effects of RVE.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jafcau/2015/jafcau.2015.63.issue-22/acs.jafc.5b01724/production/images/medium/jf-2015-01724m_0004.gif'></P>

Determination of Macelignan in Rat Plasma by High-Performance Liquid Chromatography with Ultraviolet Detection

Jin, Ming-Ji,Seo, Ki-Soo,Ha, Il-Ho,Han, Hyo-Kyung 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.7

A high-performance liquid chromatographic method was developed for the determination of macelignan in rat plasma and applied to the pharmacokinetic study of macelignan in rats. Chromatographic separation was achieved on a conventional ODS column with the mobile phase of water: acetonitrile: methanol = 35:32.5:32.5 (v/v/v %). The flow rate of isocratic elution was 1 mL/min and peaks were detected at 240 nm. The limit of detection was 10 ng/mL and the limit of quantitation was 20 ng/mL. The calibration curve was linear over the concentration range of 50-5000 ng/mL. Intra-and inter-day precision for the assay over the concentration range was below 10 % and the accuracy ranged between 96.0-107% for intra-day and 98.8-114% for inter-day, respectively. The method was applied to the single dose pharmacokinetic study of macelignan in rats and the results showed that this HPLC method was adequate to support the in vivo pharmacokinetic study of macelignan.

Liquid Chromatography-Tandem Mass Spectrometric Determination of Geniposide in Rat Plasma and its Pharmacokinetic Application

Ming Ji Jin,In Sook Kim,김동현,유혜현 대한화학회 2013 Bulletin of the Korean Chemical Society Vol.34 No.9

Geniposide is a biologically active ingredient of gardenia fruit. A liquid chromatography-tandem mass spectrometric method was developed and validated for the determination of geniposide in rat plasma. The plasma samples were pretreated by solid-phase extraction and introduced into a BDS Hypersil C18 column (50 × 2.1 mm, 5 μm) for chromatographic separation. The mobile phase consisted of 0.1% formic acid and 0.1% formic acid in acetonitrile, and gradient elution was performed at a flow rate of 0.25 mL/min. For mass spectrometric detection, multiple reaction monitoring was performed via an electrospray ionization source in positive mode. The calibration curve for geniposide was linear (r2 = 0.997) in the concentration range of 0.005- 1 μg/mL. The intra- and inter-day accuracies and precisions fulfilled the required criteria (± 15%). The developed method was subsequently used for pharmacokinetic analysis of geniposide after oral administration to rats at a dose of 50 mg/kg. The mean maximum plasma concentration of geniposide was 0.68 ± 0.29 μg/mL at 0.44 ± 0.13 h, and the mean area under the plasma concentration versus time curve was 1.46 μg·h/mL.

Predictive Factors for Non-Response to Neoadjuvant Chemotherapy for Breast Cancer

Ming Jin,Ji Young Kim,Ji Hyun Sung,Tae Hee Kim,Doo Kyung Kang,Se Hwan Han,Yong Sik Jung 한국유방암학회 2020 Journal of Breast Disease Vol.8 No.1

Purpose: Neoadjuvant chemotherapy (NAC) can effectively downstage locally advanced breast cancer; however, in some cases the cancer remains clinically stable and in others, there is disease progression. Although factors predictive of the response to NAC have been established, those for a non-response remain unknown. This study investigated factors predicting a stable or progressive disease course, and the extent of the response, after NAC based on anthracycline and cyclophosphamide (AC), with or without taxane. Methods: Data were collected retrospectively by reviewing medical records of patients who received NAC for breast cancer using AC, with or without taxane between January 2013 and December 2017. Patients with clinically stable or progressive disease after NAC were compared statistically with those who achieved a partial or complete response. Results: In total, 297 patients received NAC with AC and 196 patients received AC followed by taxane. Of these, 45 (15.2%) and 64 (32.6%) patients respectively, showed no response (i.e., stable or progressive disease). Factors related to non-response after AC included large pretreatment tumor size, clinical T3 status, and high histologic grade. Factors related to non-response after taxane included clinical T3 status and estrogen receptor or progesterone receptor positivity. Conclusion: Clinical T3 stage, grade III histological grade, and estrogen or progesterone receptor positivity were predictors of no response to NAC for breast cancer.

자연포기형 생물막-표준 활성슬러지 연계처리 시스템 개발

Ming Ji Jin,원종훈,엄진영,김성준,이순영,원찬희 대한환경공학회 2007 대한환경공학회 학술발표논문집 Vol.2007 No.12

Effects of Intestinal Microbiota on the Bioavailability of Geniposide in Rats

Jin, Ming Ji,Kim, In Sook,Kim, Dong-Hyun,Yoo, Hye Hyun American Chemical Society 2014 Journal of agricultural and food chemistry Vol.62 No.40

<P>This study investigated the effects of intestinal microbiota on the metabolism of geniposide by using a rat model treated with a mixture of antibiotics. The plasma concentration of geniposide was determined after oral administration in control and antibiotics-treated rats by using liquid chromatography–tandem mass spectrometry. The maximum plasma concentrations (<I>C</I><SUB>max</SUB>) of geniposide in control and antibiotics-treated rats were 0.91 ± 0.26 and 1.01 ± 0.04 μg/mL, respectively, and the area under the curve (AUC) values were 7.34 ± 3.32 and 11.9 ± 2.1 μg·h/mL (<I>p</I> < 0.05), respectively. The levels of geniposide in rat feces were 0.64 and 15.6 mg, respectively, in the control and antibiotics-treated groups. Thus, the systemic exposure of geniposide was greater in the antibiotics-treated rats. This may be due to the antibiotic-induced suppression of the metabolic activities of the intestinal microbiota. These results suggest that the gut microbiota may have an impact on the bioavailability of geniposide.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jafcau/2014/jafcau.2014.62.issue-40/jf502557f/production/images/medium/jf-2014-02557f_0005.gif'></P>

Determination of Macelignan in Rat Plasma by High-Performance Liquid Chromatography with Ultraviolet Detection

Ming Ji Jin,서기수,하일호,한효경 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.7

A high-performance liquid chromatographic method was developed for the determination of macelignan in rat plasma and applied to the pharmacokinetic study of macelignan in rats. Chromatographic separation was achieved on a conventional ODS column with the mobile phase of water: acetonitrile: methanol = 35:32.5:32.5 (v/v/v %). The flow rate of isocratic elution was 1 mL/min and peaks were detected at 240 nm. The limit of detection was 10 ng/mL and the limit of quantitation was 20 ng/mL. The calibration curve was linear over the concentration range of 50-5000 ng/mL. Intra-and inter-day precision for the assay over the concentration range was below 10 % and the accuracy ranged between 96.0-107% for intra-day and 98.8-114% for inter-day, respectively. The method was applied to the single dose pharmacokinetic study of macelignan in rats and the results showed that this HPLC method was adequate to support the in vivo pharmacokinetic study of macelignan.

Liquid Chromatography-Tandem Mass Spectrometric Determination of Geniposide in Rat Plasma and its Pharmacokinetic Application

Jin, Ming Ji,Kim, In Sook,Kim, Dong-Hyun,Yoo, Hye Hyun Korean Chemical Society 2013 Bulletin of the Korean Chemical Society Vol.34 No.9

Geniposide is a biologically active ingredient of gardenia fruit. A liquid chromatography-tandem mass spectrometric method was developed and validated for the determination of geniposide in rat plasma. The plasma samples were pretreated by solid-phase extraction and introduced into a BDS Hypersil $C_{18}$ column ($50{\times}2.1mm$, $5{\mu}m$) for chromatographic separation. The mobile phase consisted of 0.1% formic acid and 0.1% formic acid in acetonitrile, and gradient elution was performed at a flow rate of 0.25 mL/min. For mass spectrometric detection, multiple reaction monitoring was performed via an electrospray ionization source in positive mode. The calibration curve for geniposide was linear ($r^2=0.997$) in the concentration range of $0.005-1{\mu}g/mL$. The intra- and inter-day accuracies and precisions fulfilled the required criteria (${\pm}15%$). The developed method was subsequently used for pharmacokinetic analysis of geniposide after oral administration to rats at a dose of 50 mg/kg. The mean maximum plasma concentration of geniposide was $0.68{\pm}0.29{\mu}g/mL$ at $0.44{\pm}0.13h$, and the mean area under the plasma concentration versus time curve was $1.46{\mu}g{\cdot}h/mL$.

자연포기형 생물막공정에 의한 화학산업폐수 처리특성

김명희 ( Ming-ji Jin ),이순영 ( Soon-young Lee ),원찬희 ( Chan-hee Won ),곽규동 ( Gyu-dong Gwak ),엄진영 ( Jin-young Eom ),양기해 ( Gi-hae Yang ) 한국환경기술학회 2007 한국환경기술학회지 Vol.8 No.1

본 연구는 영세한 소규모 업체에서도 적은 비용부담으로 사용할 수 있는 오 · 폐수처리장치 개발이 필요한 실정에 맞추어 자연포기형 생물막공정을 이용한 난분해성물질을 포함한 고농도 화학산업 폐수의 유기물 용적부하와 수리학적부하에 따른 처리효율 분석을 통하여 자연포기형 생물막공정의 난분해성물질을 포함한 고농도 폐수 처리 효율성을 분석하고자 한다. 유기물 용적부하 0.2kg COD_Mn/㎥/d, 0.47kg COD_Mn/㎥/d, 0.78kg COD_Mn/㎥/d인 저율, 중율, 고율 살수여상의 운전범위에서 실험을 수행한 결과 유기물 용적부하 0.2kg COD_Mn/㎥/d, 0.47kg COD_Mn/㎥/d인 저율, 중율 살수여상의 운전범위에서 BOD₅, COD_Mn, COD_Cr 처리효율 모두 살수여상의 설계기준을 만족하며 안정적인 처리를 진행하였으나, 유기물 용적부하 0.78kg COD_Mn/㎥/d인 고율 살수여상의 운전범위에서 COD_Mn과 COD_Cr 처리효율은 설계기준에 다소 못 미치는 결과를 나타냈다. 수리학적부하 6.3㎥/㎡/d, 20.1㎥/㎡/d, 33.4㎥/㎡/d인 중속, 고속, 고속 살수여상의 수리학적부하 운전범위에서 실험을 수행한 결과 모든 운전조건에서 SS와 BOD5는 수리학적부하의 영향을 받지 않았으며, COD_Mn과 COD_Cr은 수리학적부하가 증가함에 따라 처리효율도 다소 증가하였으나 큰 영향은 받지 않았다. 따라서 경제적/효율적인 면을 동시에 만족시키기 위한 유기물 용적부하와 수리학적부하로 중율과 중속 살수여상의 운전범위에서 운전하는 것이 적정하다. In this study, natural aeration biofilm process was employed according to the requirement of development low cost-energy treatment equipment for small corporation. The efficiency of this equipment was evaluated at different organic loading rate and hydraulic loading rate to treat chemical wastewater which contains non-biodegradable matters. The chemical wastewater was treated under a trickling filter of organic loading rate at 0.2kgCOD_Mn/㎥/d, 0.47kgCOD_Mn/㎥/d and 0.78kg COD_Mn/㎥/d. when the organic loading rate is at low-rate of 0.2kg COD_Mn/㎥/d and intermediate-rate of 0.47kg COD_Mn/㎥/d, the removal efficiency of BOD₅, COD_Mn and COD_Cr can satisfied the design standard of general trickling filter process and the wastewater can be treated stably. However, when the organic loading rate is at high-rate of 0.78kg COD_Mn/㎥/d, removal efficiency of COD_Mn and COD_Cr can not satisfied the design standard of general trickling filter process. When the wastewater was treated at hydraulic loading rate of 6.3㎥/㎡/d, 20.1㎥/㎡/d and 33.4 ㎥/㎡/d, the removal efficiencies of SS and BOD₅ didn`t effected by hydraulic loading rate. While the removal efficiencies of COD_Mn and COD_Cr were increased by the increasing of by hydraulic loading rate, but the efficiencies were not distinct. To sum up, at the intermediate-rate of trickling filter, the effect of chemical wastewater treatment can be the economical and effective.