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(searched for: doi:10.1016/j.jep.2017.08.021)
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Yu Jiang, Kaibo Guo, Peipei Wang, Ying Zhu, Jiaqi Huang, Shanming Ruan
Published: 1 November 2022
Biomedicine & Pharmacotherapy, Volume 155; https://doi.org/10.1016/j.biopha.2022.113699

Yu-Ping Tang, Ding-Qiao Xu, Shi-Jun Yue, Yan-Yan Chen, Rui-Jia Fu, Xue Bai
Published: 1 July 2022
Chinese Journal of Natural Medicines, Volume 20, pp 481-493; https://doi.org/10.1016/s1875-5364(22)60206-1

Jiasong Cai, Kunlong Huang, Shengnan Han, Ruichan Chen, Zhijun Li, Yan Chen, Bing Chen, Shaoguang Li, Lin Xinhua, Hong Yao
Published: 1 July 2022
Journal: Phytomedicine
Niu Shao, Yao Xiao, Jiaxin Zhang, Yuying Zhu, Shenglong Wang,
Published: 17 January 2022
Frontiers in Pharmacology, Volume 12; https://doi.org/10.3389/fphar.2021.821567

Abstract:
Modified Sijunzi Decoction (MSJZD) is an empirical prescription of Traditional Chinese Medicine (TCM) and has been corroborated to be effective in multiple human diseases, but its role in non-small cell lung cancer (NSCLC) is enigmatic. Here we mainly analyze the function and mechanism of MSJZD in NSCLC. In this study, we used a method that coupled ultra-performance liquid chromatography to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) to investigate the major constituents in MSJZD with positive and negative ion modes. Additionally, in in vitro experiments, the effects of serum-containing MSJZD on the biological behavior of NSCLC cells induced by TGF-β1 were assessed by cell function experiments. Then, the influences of serum-containing MSJZD on epithelial-mesenchymal transition (EMT)-related markers were examined by immunofluorescence and western blot assays. Also, the AKT/GSK3β pathway and apoptosis-related markers were estimated by western blotting. Tumor xenografts were generated by subcutaneously injecting A549 cells into BALB/c nude mice to determine the effects of MSJZD in vivo. We first analyzed the composition of MSJZD. In positive ion mode, 47 kinds of components were identified. In negative ion mode, 45 kinds of components were identified. We also found that TGF-β1 contributed to inducing cell morphological changes and EMT progression. In vitro, surprisingly, cell proliferation, migration as well as invasion in NSCLC cells induced by TGF-β1, could be weakened by serum-containing MSJZD, and apoptosis was intensified. Moreover, serum-containing MSJZD weakened EMT passage and AKT/GSK3β pathway activation and induced apoptosis-related markers in NSCLC cells triggered by TGF-β1. In vivo, we discovered that MSJZD attenuated the tumor growth, promoted histopathological damage, and induced apoptosis in A549 tumor-bearing mice. Importantly, MSJZD has also restrained the development of EMT, AKT/GSK3β pathway, and TGF-β1 expression levels in nude mice. These findings demonstrated that MSJZD significantly weakened NSCLC progression by modulating EMT and AKT/GSK3β pathway.
Yueying Li, Yajun Chen, Yaqi Zeng, Jie Dong, Chunlei Li, Yingjie Jia, Yonghua Zhao, Kun Wang
Evidence-Based Complementary and Alternative Medicine, Volume 2021, pp 1-8; https://doi.org/10.1155/2021/7357521

Abstract:
Background. Cancer has been considered as the leading cause of death in the world. In patients with cancer, up to 80% display a cachectic period after diagnosis. Cachexia is known to have a negative impact on function, treatment tolerance, higher rates of hospitalizations, and mortality. Anorexia is often used as a warning sign of precachexia. Long-term anorexia may lead to malnutrition and, then, accelerate the occurrence of cachexia. A safe and effective treatment, which can both improve appetite and assist nutritional support for precachexia cancer patients shows its particular important role. Methods. A retrospective analysis comparing the different therapeutic effects on precachexia cancer patients with anorexia-malnutrition. We recorded 46 patients with the improved-Sijunzi decoction combined with enteral nutrition emulsion (ISJZ group) and 35 patients with single enteral nutrition emulsion (SEN group). The different therapeutic effects of the two groups were observed by recording indicators before and 2 weeks after treatment, including patient-generated subjective global assessment score, quality of life score, Karnofsky performance status scale, Eastern cooperative oncology group scale standard and traditional Chinese medicine syndrome, daily total dietary intake, red blood cells, hemoglobin, prealbumin, albumin, total protein cholinesterase, C-reactive protein, leukocytes, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea nitrogen, and creatinine. Results. ISJZ group exhibited prominent improvement of traditional Chinese medicine syndrome (TCMS), nutritional condition, and quality of life compared with the SEN group (QOL: p=0.0001 , PG-SGA: p=0.019 , dietary intake: p=0.0001 , TCMS: p=0.0001 ). The levels of HGB ( p=0.006 ), PAlb ( p=0.001 ), Alb ( p=0.0001 ), TP ( p=0.008 ), and ChE ( p=0.0001 ) in the ISJZ group were higher than the SEN group after treatment. Moreover, the ratios of CRP/ALB ( p=0.028 ) and CRP/PALB ( p=0.005 ) in the two groups have obvious differences; they were lower for the ISJZ group than the SEN group. Conclusions. Enteral nutrition combined with ISJZ decoction is an effective treatment in precachexia cancer patients for the prevention of cachexia. This treatment therapy can alleviate the inflammatory response, improve malnutrition state, and promote the performance status. Tianjin Medical University Cancer Institute and Hospital approved this study (Trial No. 1913).
Shao-Bo Liu, Sheng-Wen Lu, Hui Sun, Ai-Hua Zhang, Hui Wang, Wen-Feng Wei, Jin-Run Han, Ya-Jing Guo,
Published: 30 July 2021
Journal: Phytomedicine
The publisher has not yet granted permission to display this abstract.
Ying Li, Xiaowei Zhou, Ming Niu, Mingyu Zhang, Qiong Gu, Wei Chen, Bin Dong, Yuanyuan Zhang, Ruisheng Li, , et al.
Evidence-Based Complementary and Alternative Medicine, Volume 2021, pp 1-8; https://doi.org/10.1155/2021/6655449

Abstract:
Background. Si Jun Zi Tang (SJZ), a four-herb Chinese medicine formula that has been described for approximately one thousand years, is often prescribed for cancer patients as a complementary therapy in China. However, the mechanism by which Si Jun Zi Tang enhances the efficacy of gefitinib is unclear. Methods. We investigated how Si Jun Zi Tang affected the pharmacokinetics of gefitinib in rats. A rapid, specific, and reliable ultra-performance liquid chromatography method with mass spectrometry was established to determine the plasma concentration of gefitinib. Results. The results showed that a single intragastrically administered dose of Si Jun Zi Tang increased the pharmacokinetic parameters of gefitinib (Cmax, 3156.13μg/L; A UC, 46281.5μg/L/h) by 3 folds in rats compared with the administration of gefitinib alone (Cmax, 1352.07μg/L; AUC, 11823.7μg/L/h). Si Jun Zi Tang could also alter the pharmacokinetics of gefitinib by prolonging the time to reach Cmax. Conclusions. Potential pharmacokinetic interactions between gefitinib and SJZ were evaluated, and SJZ extended Tmax and T1/2 and increased the Cmax and AUC of gefitinib. Long-term administration of gefitinib in combination with Si Jun Zi Tang would improve the efficacy of gefitinib.
Published: 6 July 2021
by MDPI
Journal: Molecules
Abstract:
Currently, most clinical studies in metabolomics only consider a single type of sample such as urine, plasma, or feces and use a single analytical platform, either NMR or MS. Although some studies have already investigated metabolomics data from multiple fluids, the information is limited to a unique analytical platform. On the other hand, clinical studies investigating the human metabolome that combine multi-analytical platforms have focused on a single biofluid. Combining data from multiple sample types for one patient using a multimodal analytical approach (NMR and MS) should extend the metabolome coverage. Pre-analytical and analytical phases are time consuming. These steps need to be improved in order to move into clinical studies that deal with a large number of patient samples. Our study describes a standard operating procedure for biological specimens (urine, blood, saliva, and feces) using multiple platforms (1H-NMR, RP-UHPLC-MS, and HILIC-UHPLC-MS). Each sample type follows a unique sample preparation procedure for analysis on a multi-platform basis. Our method was evaluated for its robustness and was able to generate a representative metabolic map.
, Shijiang Ma, Wenbin Nan, Hongli Chen, Qiqing Zhang
Published: 14 January 2021
Microchemical Journal, Volume 164; https://doi.org/10.1016/j.microc.2021.105944

The publisher has not yet granted permission to display this abstract.
Ting Liu, Ruiyun Li, Yue Cui, Zhiguo Yu,
Published: 1 December 2020
Journal of Pharmaceutical Analysis, Volume 10, pp 581-587; https://doi.org/10.1016/j.jpha.2019.11.007

Abstract:
A metabonomic approach involving an ultrahigh-performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry (UHPLC-FT-ICR-MS) was used to investigate the changes in the endogenous metabolites in the plasma of rats with yeast-induced pyrexia treated with Gegenqinlian decoction (GQLD), aspirin and itraconazole. The differences in the small molecule profiles of treatment using traditional Chinese medicine, etiological treatment and symptomatic treatment were elucidated. Thirty-six plasma metabolites were identified or putatively identified, and the effects of the three medicines on the thirty-six metabolites were studied. Their metabolic pathways indicated that GQLD, aspirin and itraconazole ameliorated the rats with yeast-induced pyrexia predominantly by regulating the metabolisms of phospholipid, sphingolipid, fatty acid oxidation, fatty acid amides, amino acid and glycerolipid in vivo. The pharmacodynamics and metabonomic results showed that the three medicines exhibited the therapeutic effects on pyrexia by regulating the perturbations of multiple metabolisms. The study provided a scientific basis for an in-depth understanding of the therapeutic effects of GQLD, aspirin and itraconazole on rats with yeast-induced pyrexia.
Yuqi Fan, Zhe Ma, Lulu Zhao, Wei Wang, Mengyuan Gao, Xiaohua Jia, ,
Published: 6 October 2020
Biomedicine & Pharmacotherapy, Volume 132; https://doi.org/10.1016/j.biopha.2020.110820

The publisher has not yet granted permission to display this abstract.
Lin Sun, , Yanhui Zhao, Miao Wang, Jingyi Man,
Published: 22 July 2020
Biomedical Chromatography, Volume 34; https://doi.org/10.1002/bmc.4940

Abstract:
Shaoyao Gancao decoction (SGD) is a famous Chinese traditional prescription for treating liver injury. In this research, we investigated the therapeutic effects of SGD on liver injury and its metabolic mechanisms using 1 H NMR and UPLC-MS. Serum biochemical indicators and histopathological methods were used to determine the mechanism of action of SGD in treating liver injury. An orthogonal partial least squares discriminant analysis method was used to screen potential metabolic markers, and the MetaboAnalyst and KEGG PATHWAY databases were used to find relevant metabolic pathways. A total of 26 significant metabolites were identified with significant changes in their abundance levels, and these metabolites are involved in many metabolic pathways such as amino acid and lipid metabolism. The changes in biomarker levels reveal the therapeutic effect of SGD on liver injury, which is of great significance to speculate on possible metabolic mechanisms.
Xiaowei Zhou, Ying Li, Mingyu Zhang, Junjie Hao, Qiong Gu, Haiyang Liu, Wei Chen, Yafei Shi, Bin Dong, Yuanyuan Zhang, et al.
Evidence-Based Complementary and Alternative Medicine, Volume 2019, pp 7282681-9; https://doi.org/10.1155/2019/7282681

Abstract:
Nowadays, an increasing number of patients are seriously affected by lung cancer. Si Jun Zi Tang (SJZ), a four-herb Chinese medicine formula first described approximately one thousand years ago, is often prescribed for cancer patients as a complementary therapy. But the research on the effective materials for treating cancer using SJZ was rarely reported. To solve this problem, we evaluate the inhibitory effect of 10 samples of SJZ from different origins on PC9 cells. Ultraperformance liquid chromatography (UPLC) and hierarchical cluster analysis (HCA) along with canonical correlation analysis (CCA) and bioactivity validation were used to investigate the underlying correlation between the chemical ingredients and the antiproliferative effect of SJZ on PC9 cells. The evaluation indicated that 10 batches of SJZ could inhibit proliferation of PC9 cells and there was a notable difference in pharmacological activity between the different SJZ samples. The results of CCA and multivariate statistical analysis indicated that ginsenoside Ro and ginsenoside Rg1 might be active constituents of the antiproliferative effect as determined by spectrum-effect relationships. The results showed that bioassay and spectrum-effect relationships are suitable to associate sample quality with the active ingredient associated with clinical efficacy. And our finding would provide foundation and further understanding of the quality evaluation of traditional Chinese medicine decoction.
Jing-Ming Chen, Ting-Ting Yang, Tai-Shan Cheng, Ting-Fen Hsiao, Peter Mu-Hsin Chang, , Feng-Sheng Wang, Shih-Lan Hsu, ,
Published: 1 April 2019
Journal of Ethnopharmacology, Volume 233, pp 47-55; https://doi.org/10.1016/j.jep.2018.12.035

Abstract:
The administration of ZQ-SJZ can recover tumor- and/or cisplatin-induced cachectic conditions and significantly prolong the survival of LLC-induced cachectic mice under cisplatin treatment. The profound effect of ZQ-SJZ in hampering tumor- and/or cisplatin-induced cachexia may be due to its modulation of the mitochondrial function and subsequent myogenesis. Taken together, these results demonstrated the anti-cachectic mechanism of ZQ-SJZ and its potential use as a palliative strategy to improve the efficacy of chemotherapy.
Yi Cai, , Zhibo Guan, Xue Han, Miao Wang,
Published: 18 March 2019
Biomedical Chromatography, Volume 33; https://doi.org/10.1002/bmc.4536

Abstract:
Semen descurainiae oil (SDO) is an important traditional Chinese medicine that was discovered to have the function of reducing blood lipid in recent years. Metabolomics approach of plasma, liver and kidney in rats were performed using 1H‐NMR and LC‐MS to illuminate the lower blood lipid concentration effect of SDO, and the niacin was considered as active control. The measure of total cholesterol (TC) and low‐density lipoprotein cholesterol (LDL‐C) in plasma showed that SDO treatment decreased significantly the content of TC and LDL‐C. An orthogonal partial least squares‐discriminant analysis (OPLS‐DA) approach was applied to identify different metabolic profiles of plasma, liver and kidney in rats and to detect related potential biomarkers. The results suggested the metabolic profiles of control group (Con) and hyperlipidemia group (HLM) have significant difference and the SDO and niacin group (NA) have the effective anti‐hyperlipidemia function. The biomarkers primarily concern lipid metabolism, amino acid metabolism and glycometabolism, and the change in biomarkers indicated hyperlipidemia could cause the unbalance of these metabolic pathways in vivo and the SDO reduced blood lipid by repairing amino acid metabolism and lipid metabolism.
Chunyu Li, Ming Niu, Ruilin Wang, Xiao Wei Zhou, Bin Dong, Shuya Qi, Wei Chen, Mingyu Zhang, Yafei Shi, Ruisheng Li, et al.
Published: 12 January 2019
Biomedicine & Pharmacotherapy, Volume 111, pp 1132-1140; https://doi.org/10.1016/j.biopha.2018.12.026

Abstract:
Lung cancer remains the leading cause of cancer death worldwide, and the current therapy seems to have reached a plateau due to toxicities and acquired resistance. Therefore, exploration of novel therapeutic avenues may be useful. Si Jun Zi Tang (SJZ), a four-herb Chinese medicine formula first described approximately one thousand years, is often prescribed for cancer patients as a complementary therapy. However, whether SJZ benefits cancer patients as well as the main active constituents and its regulatory mechanism in combination with anticancer drugs remains unknown. Here, we investigated the anti-lung cancer potency and underlying mechanisms of the combination of gefitinib plus SJZ in mice with Lewis lung carcinoma (LLC), using histopathology and an integrated strategy of metabolomics and network pharmacology. The results showed that SJZ significantly enhanced gefitinib suppressing tumor growth and inhibiting LLC metastasis in LLC-bearing mice. Furthermore, 9 potential metabolomics biomarkers that differentially expressed in the SJZ/gefitinib group compared to the SJZ group or gefitinib group were identified by untargeted metabolomics, mainly involved three pathways: tricarboxylic acid cycle, tyrosine and tryptophan biosynthesis metabolism and linoleic acid metabolism. Five active ingredients, kaempferol, ginsenoside Rf, caprylic acid, lauric acid and naringenin, acted directly on 9 targets and regulated 4 out of 9 metabolites. Our results indicated that SJZ enhanced the anti-lung cancer effects of gefitinib via the key targets ABCG2, ABCC1, ABAT, GSR, CYP1A2, ALOX5, CYP3A4, PLA2G1B and PLA2G2A and the key metabolites 2-oxoglutarate, taurocholic acid, oxidized glutathione and linoleic acid. This work illustrated the modulatory properties of SJZ, which enhanced the anticancer effects of gefitinib, using metabolomics and network pharmacology analyses, and provided insights into underlying the mechanism the active ingredients of SJZfor the treatment of lung cancer in combination with gefitinib.
Er-Bing Wang, Teng Liu, Xiao-Lin Lu, Jin-Fang Xu, Qian Zheng, Zheng-Bao Zhao, Ting-Li Qu
Published: 1 January 2019
Food and Agricultural Immunology, Volume 30, pp 1046-1066; https://doi.org/10.1080/09540105.2019.1663154

Abstract:
This study aims to provide a scientific basis for the comprehensive utilization of the aerial parts of Astragalus membranaceus (APAM). UPLC-Qtrap HRMS was used to identify secondary metabolites in APAM and Astragali Radix (AR), the pharmacological effects of them in N-acetyl phenylhydrazine (APH) and cyclophosphamide (Cy)-induced mice were studied by using 1H NMR-based metabolomics. The results showed that the secondary metabolites of APAM and AR were different, but that there was no difference in the contents of eight constituent flavonoids and four constituent saponins, which were 0.8800 and 4.4351 mg/g in APAM and 0.8944 and 4.6422 mg/g in AR, respectively. APAM and AR induced beneficial effects on the recovery of body weight, blood parameters, viscera indices, Na+-K+-ATPase, and Ca2+-Mg2+-ATPase, the blood-enriching mechanisms of them were probably related to valine, leucine, and isoleucine biosynthesis, D-glutamine and D-glutamate metabolism, alanine, aspartate, and glutamate metabolism, and taurine and hypotaurine metabolism.
Can Xu, Yingfeng Wang, Caidan Rezeng, , Baosheng Zhao, Xia Wang, Xiuyuan Wu, , Jianxin Chen
Published: 8 November 2018
Journal: RSC Advances
RSC Advances, Volume 8, pp 37652-37664; https://doi.org/10.1039/c8ra07058j

Abstract:
Combinatorial tissue metabolomics technique using NMR and ICP-MS to investigate the effect of RQCJ in rats.
Zhibo Guan, Miao Wang, Yi Cai, Hongmei Yang, ,
Published: 7 April 2018
Journal of Chromatography B, Volume 1086, pp 11-22; https://doi.org/10.1016/j.jchromb.2018.04.009

Abstract:
Sijunzi decoction, a renowned Chinese prescription has long been utilized to treat gastrointestinal problems. In the context of this research work, the use of Ultra high performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry was made to separate and characterize the components of Sijunzi decoction. The performance of Liquid chromatography was carried out on a C8 column (150 mm × 2.1 mm, 1.8 μm); moreover, the mobile phase were consisted of 0.2% formic acid (A) and acetonitrile (B). In accordance with the findings, characterization of 120 chemical compounds was performed by liquid chromatography with mass spectrometry. The key constituents among them included ginsenosides (in Radix Ginseng), 16 triterpene carboxylic acids (in Poria), sesquiterpenes (in Rhizoma Atractylodis Macrocephalae), triterpenesaponins (in Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle) as well as flavonoids (in Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle) in Sijunzi decoction. This research developed the bases for prospective research associated with Sijunzi decoction, together with being expected to be useful to rapidly extract and characterize the constituents in other Traditional Chinese herbal formulations.
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