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Lizhong Decoction Ameliorates Ulcerative Colitis in Mice via Regulation of Plasma and Urine Metabolic Profiling

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Chinese Journal of Integrative Medicine 2022年第11期28卷 1015-1022页

作者： WANG Ling TAO Jin-hua CHEN Yi-fan SHEN Yu-meng JIANG Shu School of Pharmacy Nantong UniversityNantong(226001)Jiangsu ProvinceChina School of Pharmacy Nanjing University of Chinese MedicineNanjing(210023)China

Objective:To elucidate the mechanism of Lizhong Decoction(LZD)in treating dextran sodium sulfate(DSS)-induced colitis in mice based on metabonomics.Methods:Thirty-six mice were randomly divided into 6 groups,including normal,model,low-(1.365 g/kg),medium-(4.095 g/kg)and high dose(12.285 g/kg)LZD and salazosulfadimidine(SASP)groups,6 mice in each group.Colitis model mice were induced by DSS admistration for 7 days,and treated with low,medium and high dose LZD extract and positive drug SASP.Metabolic comparison of DSS-induced colitis and normal mice was investigated by using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass(UPLC-Q-TOF/MS)combined with Metabolynxsoftware.Results:The metabolic profiles of plasma and urine in colitis mice were distinctly ameliorated after LZD treatment(P<0.05).Potential biomarkers(9 in serum and 4 in urine)were screened and tentatively identified.The endogenous metabolites were mainly involved in primary bile acid,sphingolipid,linoleic acid,arachidonic acid,amino acids(alanine,aspartate,and glutamate),butanoate and glycerophospholipid metabolism in plasma,and terpenoid backbone biosynthesis,glycerophospholipid and tryptophan metabolism in urine.After LZD treatment,these markers notably restored to normal levels.Conclusions:The study revealed the underlying mechanism of LZD on amelioration of ulcerative colitis based on metabonomics,which laid a foundation for further exploring the pathological and physiological mechanism,early diagnosis,and corresponding drug development of colitis.

关键词： Lizhong Decoction ulcerative colitis metabonomics biomarkers Chinese medicine

Recent advances in ultrasound-controlled fluorescence technology for deep tissue optical imaging

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Journal of Pharmaceutical Analysis 2022年第4期12卷 530-540页

作者： Rui-Lin Liu Ru-Qian Cai School of Pharmacy Xuzhou Medical UniversityXuzhou221004China Department of Pharmaceutical Analysis School of PharmacyXi'an Jiaotong UniversityXi'an710061China

Fluorescence imaging is a noninvasive and dynamic real-time imaging technique;however,it exhibits poor spatial resolution in centimeter-deep tissues because biological tissues are highly scattering media for optical radiation.The recently developed ultrasound-controlled fluorescence(UCF)imaging is a novel imaging technique that can overcome this bottleneck.Previous studies suggest that the effective contrast agent and sensitive imaging system are the two pivotal factors for generating high-resolution UCF images ex vivo and/or in vivo.Here,this review highlights the recent advances(2015e2020)in the design and synthesis of contrast agents and the improvement of imaging systems to realize high-resolution UCF imaging of deep tissues.The imaging performances of various UCF systems,including the signal-to-noise ratio,imaging resolution,and imaging depth,are specifically discussed.In addition,the challenges and prospects are highlighted.With continuously increasing research interest in this field and emerging multidisciplinary applications,UCF imaging with higher spatial resolution and larger imaging depth may be developed shortly,which is expected to have a far-reaching impact on disease surveillance and/or therapy.

关键词： Ultrasound-controlled fluorescence imaging Temperature-sensitive NIR probes High-resolution Deep tissue Molecular diagnosis

Duplex micro RNAs assay based on target-triggered universal reporter hybridization

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Journal of Pharmaceutical Analysis 2018年第4期8卷 265-270页

作者： Yinan Wang Yue Sun Choiwan Lau Jianzhong Lu School of Pharmacy Fudan University

In this paper, we designed and evaluated a duplex detection strategy for micro RNAs（mi RNAs） using universal probe-based target-triggered double hybridization and fluorescent microsphere-based assay system（x MAP array）. In the absence of target mi RNA, reporter DNA cannot hybridize stably with the immobilized capture DNA due to its low melting temperature. Only after adding target mi RNA, can reporter probe hybridize with capture probe to form a stable three-component complex. This targettriggered stable hybridization makes this method possible for highly selective and sensitive detection of multiple mi RNAs. We exemplified a quantitative detection of duplex mi RNAs with a limit of detection of40 p M. The x MAP array platform holds the potential of extending this approach to simultaneous detection of up to 100 mi RNA targets. Considering the simplicity, rapidity and multiplexing, this work promised a potential detection of multiple mi RNA biomarkers for early disease diagnosis and prognosis.

关键词： xMAP array Multiple microRNAs Target-triggered Universal reporter

Houttuynia cordata polysaccharide alleviated intestinal injury and modulated intestinal microbiota in H1N1 virus infected mice

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Chinese Journal of Natural Medicines 2019年第3期17卷 187-197页

作者： CHEN Mei-Yu LI Hong LU Xiao-Xiao LING Li-Jun WENG Hong-Bo SUN Wei CHEN Dao-Feng ZHANG Yun-Yi Department of Pharmacology School of Pharmacy Fudan University Department of Pharmacognosy School of Pharmacy Fudan University

Houttuynia cordata polysaccharide(HCP) is extracted from Houttuynia cordata, a key traditional Chinese medicine. The study was to investigate the effects of HCP on intestinal barrier and microbiota in H1N1 virus infected mice. Mice were infected with H1N1 virus and orally administrated HCP at a dosage of 40 mg×kg^(–1)×d^(–1). H1N1 infection caused pulmonary and intestinal injury and gut microbiota imbalance. HCP significantly suppressed the expression of hypoxia inducible factor-1α and decreased mucosubstances in goblet cells, but restored the level of zonula occludens-1 in intestine. HCP also reversed the composition change of intestinal microbiota caused by H1N1 infection, with significantly reduced relative abundances of Vibrio and Bacillus, the pathogenic bacterial genera. Furthermore, HCP rebalanced the gut microbiota and restored the intestinal homeostasis to some degree. The inhibition of inflammation was associated with the reduced level of Toll-like receptors and interleukin-1β in intestine, as well as the increased production of interleukin-10. Oral administration of HCP alleviated lung injury and intestinal dysfunction caused by H1N1 infection. HCP may gain systemic treatment by local acting on intestine and microbiota. This study proved the high-value application of HCP.

关键词： HIN1 influenza virus Houttuynia cordata Inflammation Intestinal Barrier Microbiota Polysaccharide

Spectrum-effect relationship between HPLC fingerprints and bioactive components of Radix Hedysari on increasing the peak bone mass of rat

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Journal of Pharmaceutical Analysis 2019年第4期9卷 266-273页

作者： Xin-Yue Chen San-Hu Gou Zhi-Qiang Shi Zhi-Yuan Xue Shi-Lan Feng School of Pharmacy Lanzhou University

The traditional Chinese medicine of Radix Hedysari plays an important role in invigorating gas for ascending, benefiting blood for promoting production of fluid, and promoting circulation for removing obstruction in collaterals, which is consistent with the principle of treatment for osteoporosis. This study is designed to investigate the bioactive components on increasing peak bone mass (PBM) by exploring the spectrum-effect relationship between chromatography fingerprints and effect. Multiple indicators are selected to evaluate the pharmacological activity. In fingerprints, 21 common peaks are obtained, five of which are identified. Furthermore, gray relational analysis (GRA) is a quantitative method of gray system theory and is used to describe the correlation degree of common peaks and pharmacological activities with relational value. 21 components are then divided into three different regions, of which ononin and calycosin play an extremely significant role in increasing PBM. In addition, factor analysis and hierarchical cluster analysis (HCA) are used to screen the optimal producing area for Radix Hedysari. This provides a comprehensive and efficient method to improve the quality evaluation of Radix Hedysari, confirming the bioactive components for PBM-enhancement and further develop its medicinal value.

关键词： Factor analysis Gray relational analysis Hierarchical cluster analysis Peak bone mass Radix Hedysari Spectrum-effect relationship

Beneficial effects of Houttuynia cordata polysaccharides on “two-hit” acute lung injury and endotoxic fever in rats associated with anti-complementary activities

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Acta Pharmaceutica Sinica B 2018年第2期8卷 218-227页

作者： Yan Lu Yun Jiang Lijun Ling Yunyi Zhang Hong Li Daofeng Chen Department of Pharmacognosy School of Pharmacy Fudan University Department of Pharmacology School of Pharmacy Fudan University

Houttuynia cordata Thunb. is a traditional herb used for clearing heat and eliminating toxins,and has also been used for the treatment of severe acute respiratory syndrome(SARS). In vitro, the crude H. cordata polysaccharides(CHCP) exhibited potent anti-complementary activity through both the classical and alternative pathways by acting on components C3 and C4 of the complement system without interfering with the coagulation system. This study was to investigate the preventive effects of CHCP on acute lung injury(ALI) induced by hemorrhagic shock plus lipopolysaccharide(LPS) instillation(two-hit)and LPS-induced fever in rats. CHCP significantly attenuated pulmonary injury in the "two-hit" ALI model by reducing pulmonary edema and protein exudation in bronchoalveolar lavage fluid(BALF). In addition, it reduced the deposit of complement activation products in the lung and improved oxidantantioxidant imbalance. Moreover, CHCP administration inhibited fever in rats, reduced the number of leukocytes and restored serum complement levels. The inhibition on the inappropriate activation of complement system by CHCP may play an important role in its beneficial effects on inflammatory diseases. The anti-complementary polysaccharides are likely to be among the key substances for the heatclearing function of H. cordata.

关键词： Houttuynia cordata Polysaccharides Fever Acute lung injury Anti-complementary

Bimetallic Fe-Co Nanoalloy Confined in Porous Carbon Skeleton with Enhanced Peroxidase Mimetic Activity for Multiple Biomarkers Monitoring

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Journal of Analysis and Testing 2023年第1期7卷 53-68页

作者： Jingjing Luo Ruilin Liu Shuchang Zhao Yuan Gao School of Pharmacy Xuzhou Medical UniversityXuzhou 221004China

Carbon-based nanozymes with multifunctional applications have attracted enormous attention,however,there is still a lack of an effective strategy for inexpensive preparation of high-active carbon-based nanozyme.We herein report a waste paperderived CoFe_(2)O_(4)/porous carbon nanozyme for the colorimetric detection of glucose and glutathione(GSH)in biofluids.The hybrid CoFe_(2)O_(4)/porous carbon material was successfully prepared via a combined impregnation,hydrolysis and carbonization method.Newly constructed CoFe_(2)O_(4)/porous carbon material with enhanced peroxidase-like activity could oxidize colorless tetramethylbenzidine(TMB)to blue oxidized TMB with adding H_(2)O_(2).A sensitive colorimetric analysis platform for monitoring the levels of glucose and GSH in biofluids was respectively developed.The proposed analytical method possessed predominant features such as low limit of detections(LODs)(0.16μmol/L for glucose and 120 nmol/L for GSH),broad linear ranges(1-200μmol/L for glucose and 1-50μmol/L for GSH),and excellent practical potential.This multipurpose platform not only provides a promising strategy for transforming waste paper into valuable carbon-based nanozyme,but also paves the way for excavating the potential biomedical and environmental applications from waste paper.

关键词： Carbon nanozyme Fe-Co nanoalloy Glucose Glutathione Colorimetric assay

Untargeted and targeted mass spectrometry reveal the effects of theanine on the central and peripheral metabolomics of chronic unpredictable mild stress-induced depression in juvenile rats

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Journal of Pharmaceutical Analysis 2023年第1期13卷 73-87页

作者： Yanru Zhu Feng Wang Jiatong Han Yunli Zhao Miao Yu Mingyan Ma Zhiguo Yu Laboratory of Pharmaceutical Analysis School of PharmacyZhejiang Pharmaceutical UniversityNingboZhejiang315100China Laboratory of Pharmaceutical Analysis School of PharmacyShenyang Pharmaceutical UniversityShenyang110016China

L-theanine has been shown to have a therapeutic effect on depression.However,whether L-theanine has an excellent preventive effect on depression in children and adolescents and what its mechanism is have not been well explained.Given the complexity of the pathogenesis of depression,this study investigated the preventive effect and mechanism of L-theanine on depression in juvenile rats by combining serum and hippocampal metabolomic strategies.Behavioral tests,hippocampal tissue sections,and serum and hippocampal biochemical indexes were studied,and the results confirmed the preventive effect of Ltheanine.Untargeted reversed-phase liquid chromatography-quadrupole-time-of-flight mass spectrometry and targeted hydrophilic interaction liquid chromatography-triple quadrupole mass spectrometry were developed to analyze the metabolism changes in the serum and hippocampus to screen for potential biomarkers related to L-theanine treatment.The results suggested that 28 abnormal metabolites in the serum and hippocampus that were considered as potential biomarkers returned to nearnormal levels after L-theanine administration.These biomarkers were involved in various metabolic pathways,mainly including amino acid metabolism and lipid metabolism.The levels of amino acids and neurotransmitters in the phenylalanine,tryptophan,and glutamic acid pathways were significantly reduced after L-theanine administration compared with chronic unpredictable mild stress-induced rats.In summary,L-theanine had a significant preventive effect on depression and achieved its preventive results on depression by regulating various aspects of the body,such as amino acids,lipids,and inflammation.This research systematically analyzed the mechanism of L-theanine in preventing depression and laid the foundation for applying L-theanine to prevent depression in children and adolescents.

关键词： L-theanine Depression Metabolomics Liquid chromatography-mass spectrometry

Alterations of Gefitinib Pharmacokinetics by Co-administration of Herbal Medications in Rats

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Chinese Journal of Integrative Medicine 2018年第6期24卷 460-466页

作者： Kwon-Yeon Weon Min Gi Kim Soyoung Shin Tae Hwan Kim Sang Hoon Joo Eunsook Ma Seok Won Jeong Sun Dong Yoo Yu Seok Youn Beom Soo Shin College of pharmacy Catholic University of Daegu School of Pharmacy Sungkyunkwan University College of pharmacy Wonkwang University

Objective： To evaluate the potential pharmacokinetic interactions of the anticancer agent gefitinib （Iressae） and the oriental medications Guipi Decoction （归脾汤, GPD, Guibi-tang in Korean） and Bawu Decoction （八物汤, BWD, Palmul-tang in Korean）. Methods： Methylceliulose （MC, control）, GPD （1,200 mg/kg）, or BWD （6,000 mg/kg） was orally administered to rats either as a single dose or multiple doses prior to gefitinib administration. To examine the effects of a single dose of the herbal medicines, gefitinib （10 mg/kg） was orally administered after 5 min or 1 h of MC or the herbal medicine pretreatments. To examine the effects of the multiple doses of the herbal medicines, gefltinib （10 mg/kg） was orally administered following 7 consecutive days of the administration of MC or each herbal medicine. The plasma concentrations of gefitinib were determined with liquid chromatography-tandem mass spectrometry assay. The plasma concentration-time profiles of gefitinib were analyzed with a noncompartmental analysis. Results： Gefitinib was rapidly absorbed and showed a mono- exponential decline with an elimination half-life of 3.7-4.1 h. The pharmacokinetics of gefitinib was not affected by GPD pretreatment. However, a significantly lower maximum plasma concentration （Crux, P〈0.05） and area under the curve （P〈0.05）, and a delayed time to reach Cmax （Tmax, P〈0.01） were observed in both single- and multiple- dose BWD-pretreated rats compared with the control rats. Conclusions： BWD and not GPD might delay and interfere with gefitinib absorption. Further evaluations of the clinical significance of these findings are needed.

关键词： herb-drug interaction pharmacokinetics gefitinib Guipi Decoction Bawu Decoction