Publications by authors named "Wenyuan Gao"

184 Publications

Nanoparticle conjugation of ginsenoside Rb3 inhibits myocardial fibrosis by regulating PPARα pathway.

Biomed Pharmacother 2021 May 1;139:111630. Epub 2021 May 1.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, PR China. Electronic address:

Background: Cardiac fibrosis occurs in ischemic and non-ischemic heart failure, hereditary cardiomyopathy, diabetes and aging. Energy metabolism, which serves a crucial function in the course and treatment of cardiovascular diseases, might have therapeutic benefits for myocardial fibrosis. Ginsenoside Rb3 (G-Rb3) is one of the main components of Ginseng and exhibits poor oral bioavailability but still exerts regulate energy metabolism effects in some diseases. Therefore, the study investigated the effect of chitosan (CS) @ sodium tripolyphosphate (TPP) nanoparticles conjugation with ginsenoside Rb3 (NpRb3) on myocardial fibrosis and studied its possible mechanisms. The results showed that NpRb3 directly participates in the remodeling of myocardial energy metabolism and the regulation of perixisome proliferation-activated receptor alpha (PPARα), thereby improving the degree of myocardial fibrosis. The study also verifies the protective effect of NpRb3 on energy metabolism and mitochondrial function by targeting the PPARα pathway. Therefore, the prepared nanodrug carrier may be a potential solution for the delivery of G-Rb3, which is a promising platform for oral treatment of myocardial fibrosis.
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http://dx.doi.org/10.1016/j.biopha.2021.111630DOI Listing
May 2021

Tissue distribution, metabolism and absorption of Rhizoma Paridis Saponins in the rats.

J Ethnopharmacol 2021 Jun 19;273:114038. Epub 2021 Mar 19.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Weijin Road, Tianjin, 300072, China. Electronic address:

Ethnopharmacological Relevance: Paris polyphylla var yunnanensis as a traditional Chinese medicine has been used in the treatment of liver disease for thousands of years. Rhizoma Paridis saponins (RPS) were the main active ingredients in Paris polyphylla with an excellent antitumor effect. However, metabolic and distribution of RPS has not been known.

Aim Of The Study: The objective of this study was to research metabolic and distribution of RPS.

Materials And Methods: In this study, the separation and simultaneous determination of RPS in rat plasma and tissues were developed and validated by LC-MS/MS. The permeability and recovery of RPS were tested by Caco-2. S9 assay suggested the metabolic mode of RPS in rats.

Results: After oral administration of RPS, the metabolic compound like diosgenin was detected in different tissues although there was none in RPS. The concentration of PI, PII, PVI, PVII, PH and gracillin in the spleen was the highest among these organs. The content of diosgenin were the highest in lung and brain. Caco-2 test indicated that PI, PII, PVI and PVII were low permeability and low recovery. Efflux ratio indicated that PVI should be a potential P-gp substrate. Potential P-gp substrate may be PVI. S9 assay suggested that RPS possess slow metabolic and moderate metabolic compounds.

Conclusions: Integrated LC-MS/MS analysis of serum samples, together with Caco-2 and S9 assays provided a theoretical basis for the application of RPS in the future.
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http://dx.doi.org/10.1016/j.jep.2021.114038DOI Listing
June 2021

Pharmacokinetics profiles of polyphyllin II and polyphyllin VII in rats by liquid chromatography with tandem mass spectrometry.

Biomed Chromatogr 2021 Feb 5:e5083. Epub 2021 Feb 5.

Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.

Polyphyllin II (PII) and polyphyllin VII (PVII) are the main active ingredients in Paris Polyphylla with an excellent antitumor effect in vitro and in vivo. In this study, a rapid and precise LC-MS/MS method was developed and validated for the separation and simultaneous determination of PII and PVII in rat plasma, tissues, feces and urine using ginsenoside Rg3 as the internal standard. Positive linearity ranged from 1 to 1,000 ng/ml in samples. At the same time, intra- and inter-day precisions were in range of 1.8-12.0%. The accuracy ranged from 95.9 to 100.8%. Mean extraction recoveries of PII and PVII ranged from 86.6 to 96.4%. The analytical method has been successfully applied to the pharmacokinetic studies of PII and PVII in rats after their i.v. administration. After entering systemic circulation, PII and PVII were rapidly distributed in organs, mainly including liver, lung and spleen. Their elimination rate was slow. All of these data provided a theoretical basis for the application of PII and PVII in the treatment of liver- and lung-related diseases.
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http://dx.doi.org/10.1002/bmc.5083DOI Listing
February 2021

Endophytes, biotransforming microorganisms, and engineering microbial factories for triterpenoid saponins production.

Crit Rev Biotechnol 2021 Mar 20;41(2):249-272. Epub 2021 Jan 20.

Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.

Triterpenoid saponins are structurally diverse secondary metabolites. They are the main active ingredient of many medicinal plants and have a wide range of pharmacological effects. Traditional production of triterpenoid saponins, directly extracted from cultivated plants, cannot meet the rapidly growing demand of pharmaceutical industry. Microorganisms with triterpenoid saponins production ability (especially genus) and biotransformation ability, such as fungal species in and genera and bacterial species in and Intestinal microflora, represent a valuable source of active metabolites. With the development of synthetic biology, engineering microorganisms acquired more potential in terms of triterpenoid saponins production. This review focusses on potential mechanisms and the high yield strategies of microorganisms with inherent production or biotransformation ability of triterpenoid saponins. Advances in the engineering of microorganisms, such as , , and , for the biosynthesis triterpenoid saponins have also been reported. Strategies to increase the yield of triterpenoid saponins in engineering microorganisms are summarized following four aspects, that is, introduction of high efficient gene, optimization of enzyme activity, enhancement of metabolic flux to target compounds, and optimization of fermentation conditions. Furthermore, the challenges and future directions for improving the yield of triterpenoid saponins biosynthesis in engineering microorganisms are discussed.
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http://dx.doi.org/10.1080/07388551.2020.1869691DOI Listing
March 2021

Hydrocarbon Degradation and Enzyme Activities of and Isolated from Nigerian Crude Oil-Polluted Sites.

Microorganisms 2020 Nov 30;8(12). Epub 2020 Nov 30.

School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, China.

Many free-living saprobic fungi are nature recruited organisms for the degradation of wastes, ranging from lignocellulose biomass to organic/inorganic chemicals, aided by their production of enzymes. In this study, fungal strains were isolated from contaminated crude-oil fields in Nigeria. The dominant fungi were selected from each site and identified as and based on morphological and molecular characterization, with site percentage incidences of 56.67% and 66.70%, respectively. Selected strains response/tolerance to complex hydrocarbon (used engine oil) was studied by growing them on Bushnell Haas (BH) mineral agar supplemented with the hydrocarbon at different concentrations, i.e., 5%, 10%, 15%, and 20%, with a control having dextrose. Hydrocarbon degradation potentials of these fungi were confirmed in BH broth culture filtrates pre-supplemented with 1% engine oil after 15 days of incubation using GC/MS. In addition, the presence of putative enzymes, laccase (Lac), manganese peroxidase (MnP), and lignin peroxidase (LiP) was confirmed in culture filtrates using appropriate substrates. The analyzed fungi grew in hydrocarbon supplemented medium with no other carbon source and exhibited 39.40% and 45.85% dose inhibition response (DIR) respectively at 20% hydrocarbon concentration. An enzyme activity test revealed that these two fungi produced more Lac than MnP and LiP. It was also observed through the GC/MS analyses that while acted on all hydrocarbon components in the used engine oil, only degraded the long-chain hydrocarbons and BTEX. This study confirms that and have the potential to be exploited in the bio-treatment and removal of hydrocarbons from polluted soils.
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http://dx.doi.org/10.3390/microorganisms8121912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761101PMC
November 2020

Shunaoxin pills improve the antihypertensive effect of nifedipine and alleviate its renal lipotoxicity in spontaneous hypertension rats.

Environ Toxicol 2021 Mar 24;36(3):386-395. Epub 2020 Oct 24.

Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.

Shunaoxin pills (SNX) have been used to treat cerebrovascular diseases in China since 2005. Hypertension is a major risk factor for cerebrovascular disease. This study aimed to explore the synergistic antihypertensive effect of SNX and nifedipine and whether SNX could alleviate nifedipine-induced renal lipotoxicity. During administration, systolic blood pressure was measured weekly. After 5 weeks administration, we examined pathological changes of kidney, renal function, the lipid metabolism index, and adipogenesis genes expression in the kidney tissues, and explored its underlying mechanism. Finally, network pharmacology was used for supplement and verification. As a result, SNX improved the antihypertensive effect of nifedipine and apparently improved nifedipine-induced renal pathological changes, dyslipidemia and the levels of adipogenesis gene expression in kidney tissues. SNX reduced the levels of interleukin-6 and interleukin-1β in renal tissues, down-regulated the production of malondialdehyde, and increased superoxide dismutase activity and the protein expression of heme oxygenase-1 in kidney tissues. Network pharmacology also showed that SNX could improve nifedipine-induced renal lipotoxicity. The combination of SNX and nifedipine had certain benefits in the treatment of hypertension.
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http://dx.doi.org/10.1002/tox.23044DOI Listing
March 2021

Paris saponin II-induced paraptosis-associated cell death increased the sensitivity of cisplatin.

Toxicol Appl Pharmacol 2020 11 21;406:115206. Epub 2020 Aug 21.

Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

Paris Saponin II (PSII) has been regarded as an effective and imperative component isolated from Rhizoma Paridis saponins (RPS) and exhibited strong anti-tumor effects on a variety of cancer. Our results revealed that human non-small lung cancer cell lines NCI-H460 and NCI-H520 were exposed to 1 μM of PSII, which inhibited the proliferation of lung cancer cells and activated apoptosis, autophagy and paraptosis. PSII induced paraptosis-associated cell death prior to apoptosis and autophagy. It induced paraptosis based on ER stress through activation of the JNK pathway. Meanwhile, PSII increased the cytotoxicity of cisplatin through paraptosis-associated pathway. All in all, PSII induced paraptosis based on induction of non-apoptotic cell death, which would be a possible approach to suppress the multi-drug resistant to apoptosis.
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http://dx.doi.org/10.1016/j.taap.2020.115206DOI Listing
November 2020

Integrated Phytochemical Analysis Based on UPLC-MS and Network Pharmacology Approaches to Explore the Quality Control Markers for the Quality Assessment of L.

Molecules 2020 Aug 20;25(17). Epub 2020 Aug 20.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.

Red clover consists of the overground parts and inflorescence of L., a leguminous plant belonging to the genus . It is widely distributed worldwide and has long been used in traditional medicine. In this study, a combination approach using UPLC-MS and network pharmacology was applied to explore the quality control markers for the quality assessments of red clover. Firstly, UPLC-MS was used to identify the compounds in different parts of red clover. Twenty-eight compounds were totally identified. According to the traditional clinical efficacy of red clover, a compound-target-function network was constructed by network pharmacology to discover the main active compounds based on the identified compounds. Nine compounds of chlorogenic acid, daidzin, calycosin-7--β-d-glucoside, genistin, ononin, daidzein, genistein, formononetin, and biochanin A were filtrated and further confirmed in rat plasma in view of the blood-absorbed components taking effects. Finally, a novel method for simultaneously detecting the nine quality control markers was developed by UPLC-QQQ-MS in an effort to assess the quality of red clover. For all samples, the average contents of the nine compounds measured from high to low consist of formononetin, ononin, biochanin A, genistin, daidzin, calycosin-7--β-d-glucoside, genistein, daidzein, and chlorogenic acid. The samples from Gansu province showed the best quality in the three producing areas This study provides new strategies to explore the quality control markers and develops a novel method for the quality assessment of red clover.
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http://dx.doi.org/10.3390/molecules25173787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504318PMC
August 2020

Molecular evidence supports simultaneous association of the achlorophyllous orchid Chamaegastrodia inverta with ectomycorrhizal Ceratobasidiaceae and Russulaceae.

BMC Microbiol 2020 08 3;20(1):236. Epub 2020 Aug 3.

AgroBioSciences and Chemical & Biochemical Sciences Department, University Mohammed VI Polytechnic, Hay Moulay Rachid, Ben Guerir, Morocco.

Background: Achlorophyllous orchids are mycoheterotrophic plants, which lack photosynthetic ability and associate with fungi to acquire carbon from different environmental sources. In tropical latitudes, achlorophyllous forest orchids show a preference to establish mycorrhizal relationships with saprotrophic fungi. However, a few of them have been recently found to associate with ectomycorrhizal fungi and there is still much to be learned about the identity of fungi associated with tropical orchids. The present study focused on mycorrhizal diversity in the achlorophyllous orchid C. inverta, an endangered species, which is endemic to southern China. The aim of this work was to identify the main mycorrhizal partners of C. inverta in different plant life stages, by means of morphological and molecular methods.

Results: Microscopy showed that the roots of analysed C. inverta samples were extensively colonized by fungal hyphae forming pelotons in root cortical cells. Fungal ITS regions were amplified by polymerase chain reaction, from DNA extracted from fungal mycelia isolated from orchid root samples, as well as from total root DNA. Molecular sequencing and phylogenetic analyses showed that the investigated orchid primarily associated with ectomycorrhizal fungi belonging to a narrow clade within the family Ceratobasidiaceae, which was previously detected in a few fully mycoheterotrophic orchids and was also found to show ectomycorrhizal capability on trees and shrubs. Russulaceae fungal symbionts, showing high similarity with members of the ectomycorrhizal genus Russula, were also identified from the roots of C. inverta, at young seedling stage. Ascomycetous fungi including Chaetomium, Diaporthe, Leptodontidium, and Phomopsis genera, and zygomycetes in the genus Mortierella were obtained from orchid root isolated strains with unclear functional role.

Conclusions: This study represents the first assessment of root fungal diversity in the rare, cryptic and narrowly distributed Chinese orchid C. inverta. Our results provide new insights on the spectrum of orchid-fungus symbiosis suggesting an unprecedented mixed association between the studied achlorophyllous forest orchid and ectomycorrhizal fungi belonging to Ceratobasidiaceae and Russulaceae. Ceratobasidioid fungi as dominant associates in the roots of C. inverta represent a new record of the rare association between the identified fungal group and fully mycoheterotrophic orchids in nature.
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http://dx.doi.org/10.1186/s12866-020-01906-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397628PMC
August 2020

Quality by Design-Based Assessment for Analytical Similarity of Adalimumab Biosimilar HLX03 to Humira®.

AAPS J 2020 05 8;22(3):69. Epub 2020 May 8.

Shanghai Engineering Research Center of Anti-tumor Biologic Drugs, Shanghai Henlius Biotech Inc., Shanghai, China.

Quality by design (QbD) is an efficient but challenging approach for the development of biosimilar due to the complex relationship among process, quality, and efficacy. Here, the analytical similarity of adalimumab biosimilar HLX03 to Humira® was successfully established following a QbD quality study. Quality target product profile (QTPP) of HLX03 was first generated according to the public available information and initial characterization of 3 batches of Humira®. The critical quality attributes (CQAs) were then identified through risk assessment according to impact of each quality attribute on efficacy and safety. The anticipated range for each CQA was derived from similarity acceptance range and/or the corresponding regulatory guidelines. Finally, a panel of advanced and orthogonal physicochemical and functional tests and comparison of 6 batches of HLX03 and 10 batches of the reference standard demonstrated high similarity of HLX03 to Humira®, except for slightly lower percentage of high mannosylated glycans (%HM) in HLX03 which had no effect on FcγRIII binding and antibody-dependent cell-mediated cytotoxicity (ADCC) activity in human peripheral blood mononuclear cell (PBMC). All above demonstrated the feasibility and efficiency of QbD-based similarity assessment of a biosimilar monoclonal antibody (mAb).
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http://dx.doi.org/10.1208/s12248-020-00454-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210234PMC
May 2020

Comparative studies on characterization, saccharide mapping and antiglycation activity of polysaccharides from different Polygonatum ssp.

J Pharm Biomed Anal 2020 Jul 6;186:113243. Epub 2020 Mar 6.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300193, China. Electronic address:

Multiple species of Polygonatum are used as "Huangjing" in China and polysaccharides are the main effective constituents of "Huangjing". However, there is a lack of systematic comparison of polysaccharides from Polygonatum spp., and little work concerning on the polysaccharides from unofficial species. This paper conducted a comparison study on the characterization, high-performance gel permeation chromatography (HPGPC) saccharide mapping and antiglycation assay of polysaccharides and their enzymatic hydrolysates from nine species of Polygonatum. The results showed that polysaccharides from P. macropodium were mainly composed of fructans (3.3 × 10 Da); while polysaccharides from other eight Polygonatum spp. contained both fructans (2.5 × 10-4.1 × 10 Da) and pectins (more than 4.1 × 10 Da). Antiglycation assay showed that polysaccharides from Polygonatum spp. could significantly inhibit the formation of AGEs, and degradation of pectins and fructans could result in loss of activity. The results are helpful to the rational usage and quality control of Polygonatum spp.
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http://dx.doi.org/10.1016/j.jpba.2020.113243DOI Listing
July 2020

Demonstrating Analytical Similarity of Trastuzumab Biosimilar HLX02 to Herceptin with a Panel of Sensitive and Orthogonal Methods Including a Novel FcγRIIIa Affinity Chromatography Technology.

BioDrugs 2020 Jun;34(3):363-379

Shanghai Engineering Research Center of Anti-tumor Biologic Drugs, Shanghai Henlius Biotech., Inc., Shanghai, China.

Background: A biosimilar needs to demonstrate its similarity to the originator reference product (RP) in terms of structural and functional properties as well as nonclinical and clinical outcomes.

Objectives: The aim was to assess the analytical similarity between the trastuzumab biosimilar HLX02 and Europe-sourced Herceptin (EU-Herceptin) and China-sourced Herceptin (CN-Herceptin) following a quality-by-design (QbD) quality study and tier-based quality attribute evaluation.

Methods: A panel of highly sensitive and orthogonal methods, including a novel Fc gamma receptor IIIa (FcγRIIIa) affinity chromatography technique that enables quantitative comparison of glycan effects on effector function, was developed for the assessment. To ensure the full product variability was captured, ten batches of HLX02 were compared with 39 RP batches with expiry dates from August 2017 to March 2021.

Results: The extensive three-way similarity assessment demonstrated that HLX02 is highly similar to the RPs. Furthermore, the %afucose, %galactose, and FcγRIIIa affinity of the RPs were observed to first decrease and then return to the original level in relation to their expiry dates, and the RP batches can be subgrouped by their FcγRIIIa affinity chromatograms. HLX02 is demonstrated to be more similar to the RPs of the high FcγRIIIa affinity group.

Conclusion: Besides having an overall high analytical similarity to both EU-Herceptin and CN-Herceptin, HLX02 is more similar to Herceptin with high FcγRIIIa affinity, a result that demonstrates the power of the novel FcγRIIIa affinity chromatography technology in biosimilarity evaluation.
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http://dx.doi.org/10.1007/s40259-020-00407-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211197PMC
June 2020

Characterisation and saccharide mapping of polysaccharides from four common Polygonatum spp.

Carbohydr Polym 2020 Apr 11;233:115836. Epub 2020 Jan 11.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300193, China. Electronic address:

Polysaccharides from 14 batches of Polygonatum sibiricum (PS), P. cyrtonema (PC), P. kingianum (PK) and P. odoratum (PO) were compared based on high-performance gel permeation chromatography (HPGPC) saccharide mapping, monosaccharide composition, molecular weight distribution and Fourier transform infrared (FTIR) spectra. Results showed that polysaccharides from PS, PC and PK exhibited two different molecular weight fractions and that one was more than 4.1 × 10 Da (P1) and the other was 2.8-5.4 × 10 Da (P2); while the polysaccharides from PO displayed only one main peak (P2). The analysis of monosaccharide composition and HPGPC saccharide mapping proved that P1 and P2 were composed of pectins and fructans, respectively. The FTIR spectra indicated that these polysaccharides had different degrees of esterification. This study provided a systematic profiling of polysaccharides of Polygonatum spp. and was helpful in understanding the varied functions of different Polygonatum spp., based on chemical composition.
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http://dx.doi.org/10.1016/j.carbpol.2020.115836DOI Listing
April 2020

Antihypertensive and renal protective effect of Shunaoxin pill combined with captopril on spontaneous hypertension rats.

Biomed Pharmacother 2020 May 4;125:109977. Epub 2020 Feb 4.

Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China. Electronic address:

Introduction: According to previous reports, hypertension has become the most common chronic disease in the world. Captopril, an angiotensin-converting enzyme inhibitor, has been widely used for the therapy of arterial hypertension and cardiovascular diseases therapy. Besides, Shunaoxin pill (SNX) as a traditional Chinese prescription showed antihypertensive effect in our previous research.

Objective: This study means to investigate whether SNX combining with captopril could show antihypertensive and renal protective effects on spontaneous hypertension rats (SHRs).

Methods: SHRs were randomly assigned to four treatment groups, including non-treated group, captopril, SNX, and captopril + SNX-treated groups. Their body weight and systolic blood pressure (SBP) were measured weekly. Histopathological examination was analyzed through Masson staining and hematoxylin and eosin staining. Biochemical analyses, ELISA, and western blot were used to analyze their combining mechanism.

Results: In this experiment, this combinatorial therapy significantly reduced aortic wall thickness, increased the content of NO, NOS and eNOS, decreased the content of bradykinin and endothelin 1(ET-1), and regulated the levels of TG, TC and HDLC back to normal, which suggested they could induce vasodilation and lower blood pressure. Meanwhile, histological examination alleviated that captopril + SNX remarkably inhibited renal injury, including tubular disorder, inflammatory cell infiltration and fibrosis. They down-regulated the serum levels of BUN and Cr, protein expression of IL-1β, NF-κB, Bax, Cyt c, caspase 3, 8 and 9 in kidney tissues and significantly increased the levels of Bcl-2 in kidney tissues compared with monotherapy group.

Conclusion: The combinatorial treatment of SNX and captopril lowered blood pressure through adjusting NO/NOS, ET-1 and dyslipidemia profile. Furthermore, this treatment alleviated the kidney damage via reducing the release of inflammatory factors and the expression of apoptotic markers. Therefore, these results provided a rationale for future clinical use of SNX combined with captopril in antihypertensive and protecting renal functions in hypertension.
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http://dx.doi.org/10.1016/j.biopha.2020.109977DOI Listing
May 2020

New data highlighting the efficacy and safety outcomes of third-generation EGFR-TKI in NSCLC patients with rare EGFR mutations.

Thorac Cancer 2020 03 28;11(3):495-497. Epub 2020 Jan 28.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.

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http://dx.doi.org/10.1111/1759-7714.13334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049494PMC
March 2020

Multi-dimensional templated synthesis of hierarchical FeO/NiO composites and their superior ethanol sensing properties promoted by nanoscale p-n heterojunctions.

Dalton Trans 2020 Jan;49(4):1300-1310

School of Textile and Material Engineering, Dalian Polytechnic University, Dalian 116034, China.

A hierarchical NiO-based nanostructure, constructed from multi-dimensional building blocks, was fabricated by a synthesis method based on electrospinning and solution phase reaction. Fe was incorporated into the NiO nanostructure with highly uniform distribution via ion exchange reaction. A series of Fe2O3/NiO composites with different compositions were successfully synthesized with the hierarchical architecture well preserved. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDS) and inductively coupled plasma-optical emission spectrometry (ICP-OES) were used to characterize the structure and to confirm the formation mechanism of the synthesized products. The gas sensing properties of the Fe2O3/NiO hierarchical composites were systematically investigated. The optimized composition of Fe2O3/NiO shows superior sensing performance towards ethanol, such as high sensitivity, fast response/recovery speed and good selectivity. The high gas sensing performance of the sensing material was mainly due to the completeness of the heterojunction assembly between n-type Fe2O3 and p-type NiO, as well as the amplification effect caused by assembling the heterojunctions on the nanoscale.
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http://dx.doi.org/10.1039/c9dt04185kDOI Listing
January 2020

In vivo flow cytometry combined with intravital microscopy to monitor kinetics of transplanted bone marrow mononuclear cells in peripheral blood and bone marrow.

Mol Biol Rep 2020 Jan 7;47(1):1-10. Epub 2019 Dec 7.

Department of Hematology, Huashan Hospital, Fudan University, Shanghai, 200040, China.

Bone marrow mononuclear cells (BM-MNCs) transplantation has evolved as a promising experimental treatment in various regenerative therapy fields, especially in clinical hematopoietic stem cells transplantation (HSCT). In vitro methods have mainly been used to study the pre-clinical kinetics of BM-MNCs in mice after transplantation. And it is difficult to monitor the dynamic homing of BM-MNCs in living mice. The present study obtained the kinetics of transplanted BM-MNCs in the peripheral blood (PB) and the dynamic homing of BM-MNCs in the BM in living mice by a combination of in vivo flow cytometry (IVFC) and calvarium intravital microscopy. We found out that BM-MNCs were cleared rapidly from the PB and mainly localized to various hematopoietic tissues after transplantation. The number of BM-MNCs in the PB decreased over time accompanied by an increase in the BM indeed after transplantation. In addition, a lower number of BM-MNCs were found home to calvaria than long bone, probably indicating long bone marrow might also be an important hematopoietic organ. Clinical studies will benefit from non-invasive measurements to monitor the dynamic homing of transplanted cells. Our pre-clinical kinetics of BM-MNCs in living mice will have important clinical guiding significance in HSCT and other regenerative therapy fields.
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http://dx.doi.org/10.1007/s11033-019-04608-xDOI Listing
January 2020

Effect of brachial-ankle pulse wave velocity combined with blood pressure on cardio-cerebrovascular events.

Exp Ther Med 2019 Dec 30;18(6):4555-4566. Epub 2019 Oct 30.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, P.R. China.

The aim of the present study was to evaluate the effect of brachial-ankle pulse wave velocity (baPWV) combined with blood pressure (BP) on cardio-cerebrovascular events. Participants who received health examinations during the periods 2010-2011, 2012-2013 and 2014-2015 were recruited. The participants were divided into four groups according to their BP and baPWV levels as follows: Normotension + low baPWV, normotension + high baPWV, hypertension + low baPWV, and hypertension + high baPWV. The cumulative incidence of cardio-cerebrovascular events was calculated using life-table analysis, and the associations of BP and baPWV with cardio-cerebrovascular events were analyzed using a multivariate Cox proportional hazards regression model. Receiver operating characteristic curves were used to calculate the predictive values of baPWV combined with BP, baPWV alone or BP alone for cardio-cerebrovascular events by comparing their area under the curve (AUC) using the normal approximation method. There were 20,310 participants with a mean age of 50.13±0.09 years in the present study, including 13,240 males. A total of 278 participants developed a cardio-cerebrovascular event after a mean follow-up period of 3.34±1.82 years. The cumulative incidence of cardio-cerebrovascular events in the normotension + low baPWV, normotension + high baPWV, hypertension + low baPWV and hypertension + high baPWV groups was 0.2, 0.9, 0.8 and 3.1%. Multivariate Cox proportional hazards regression analysis showed that compared with the normotension + low baPWV group, the risks of cardio-cerebrovascular events in the normotension + high baPWV, hypertension + low baPWV and hypertension + high baPWV groups were increased after adjusting for confounding factors, and their hazard ratios (95% CI) were 4.18 (2.23-7.83), 3.00 (1.39-6.47) and 9.34 (5.14-16.96), respectively. The AUC values for the predictive values of baPWV combined with BP, baPWV alone and BP alone on cardio-cerebrovascular events were calculated to be 0.744, 0.677 and 0.698, respectively. In conclusion, high baPWV accompanied by hypertension could increase the risk of cardio-cerebrovascular events. The predictive value of baPWV combined with BP on cardio-cerebrovascular events is superior compared with that of either baPWV or BP alone.
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http://dx.doi.org/10.3892/etm.2019.8149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878894PMC
December 2019

The anti-inflammatory effects of formononetin and ononin on lipopolysaccharide-induced zebrafish models based on lipidomics and targeted transcriptomics.

Metabolomics 2019 11 25;15(12):153. Epub 2019 Nov 25.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.

Introduction: Formononetin (MBHS) and its glycosylated derivative ononin (MBHG), as the major isoflavones, have exhibited the anti-inflammatory impacts on the lipopolysaccharide (LPS)-induced inflammation. Although various researches have focused on interpreting the pharmaceutical activities of MBHG and MBHS, the molecular mechanisms in zebrafish models are still unclear.

Objective: The purpose of the present work is to investigate the molecular mechanisms of the anti-inflammatory effects of MGHG and MBHS based on lipidomics and targeted transcriptomics.

Methods: UHPLC-MS was applied for the lipid analyses and RT-PCR was adopted for the mRNA analyses, and the results of different groups were compared for exploring the significantly changed lipids and mRNAs.

Results: The results of lipidomics revealed that phosphatidylcholines (PCs) were drastically down-regulated in the MBHG or MBHS treated LPS-induced inflammatory zebrafish models. Besides, MBHS can also decrease the levels of triacylglycerols (TAGs). For the targeted transcriptomics analyses, 4 cytokines (TNF-α, IL-1β, IL-6 and IFN-γ) and 3 mRNA (JNK1, ERK1 and p38a) involved in the MAPK pathway were down-regulated and IL-10 was up-regulated under the treatment of MBHG or MBHS.

Conclusion: Combining the results of lipidomics and targeted transcriptomics, we indicated that MBHG and MBHS exerted potent anti-inflammatory effects on the LPS-induced zebrafish models through the MyD88 or TRIF MAPK/ERK and MAPK/JNK pathways and the glycerophospholipid, glycosylphosphatidylinositol (GPI)-anchor biosynthesis and glycerolipid metabolisms. Our results provided new insights into the anti-inflammatory mechanisms of MBHG or MBHS and supplied an effective method to interpret the pharmacological mechanisms of drugs.
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http://dx.doi.org/10.1007/s11306-019-1614-2DOI Listing
November 2019

Diosgenyl Saponin Inducing Endoplasmic Reticulum Stress and Mitochondria-Mediated Apoptotic Pathways in Liver Cancer Cells.

J Agric Food Chem 2019 Oct 7;67(41):11428-11435. Epub 2019 Oct 7.

Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology , Tianjin University , Tianjin 300072 , People's Republic of China.

Diosgenin and diosgenyl saponins as the major bioactive compounds isolated from dietary fenugreek seeds, yam roots, etc. possessed strong antitumor effects. To understand their detailed antitumor mechanisms, a fluorophore-appended derivative of diosgenin [Glc/CNHphth-diosgenin (GND)] was synthesized, starting from diosgenin and glucosamine hydrochloride in overall yields of 7-12% over 7-10 steps. Co-localization of GND with organelle-specific stains, transmission electron microscopy, and relative protein analyses demonstrated that GND crossed the plasma membrane through organic anion-transporting polypeptide 1B1 and distributed in the endoplasmic reticulum (ER), lysosome, and mitochondria. In this process, GND induced ER swelling, mitochondrial damage, and autophagosome and upregulating IRE-1α to induce autophagy and apoptosis. Furthermore, autophagy inhibitor chloroquine delayed the appearance of cleaved poly(ADP-ribose) polymerase and inhibited cleaved caspase 8, which indicated that GND induced autophagy to activate caspase-8-dependent apoptosis. These observations suggested that diosgenyl saponin was a potent anticancer agent that elicited ER stress and mitochondria-mediated apoptotic pathways in liver cancer.
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http://dx.doi.org/10.1021/acs.jafc.9b05131DOI Listing
October 2019

Quality evaluation of Panax ginseng adventitious roots based on ginsenoside constituents, functional genes, and ferric-reducing antioxidant power.

J Food Biochem 2019 08 29;43(8):e12901. Epub 2019 May 29.

Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, People's Republic of China.

In the study, six adventitious root lines of Panax ginseng have been successfully established. HPLC-ESI-MS analysis showed that 20 ginsenosides were identified in root lines, notoginsenoside Fa and notoginsenoside R were not found in AR lines. In AR lines, the highest accumulation of total ginsenosides was obtained in five-year main AR (24.87 mg/g). Principal component analysis classified root lines into three groups. Five-year ginseng was mostly similar with five-year main AR, five-year rootlet AR, and four-year rootlet AR in ginsenosides composition of group 1. Besides, gene expressions were consistent with the production of total ginsenosides, and correlation analysis revealed that total ginsenosides biosynthesis was significantly positively correlated with the gene expression of dammarenediol synthase. Five-year rootlet AR showed the highest activity on ferric-reducing antioxidant power test among samples. It provides a scientific evidence for the further exploitation and large-scale production of P. ginseng. PRACTICAL APPLICATIONS: This study provides valuable information for the commercial scale culture of ginseng adventitious roots. This report combines morphology, ginsenoside composition and content, gene expression, and ferric-reducing antioxidant power test to evaluate the quality of P. ginseng adventitious root, and combined with principal component analysis to screen out the high yield and stable ginseng adventitious roots. It would be profitable to use adventitious root culture of P. ginseng instead of field cultivation.
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http://dx.doi.org/10.1111/jfbc.12901DOI Listing
August 2019

Chemotaxonomic studies of 12 Dioscorea species from China by UHPLC-QTOF-MS/MS analysis.

Phytochem Anal 2020 Mar 31;31(2):164-182. Epub 2019 Jul 31.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China.

Introduction: Dioscorea species, which contain abundant steroidal saponins, have been used as folk medicines or raw materials to synthesise steroid drugs.

Objective: To establish a rapid chemotaxonomic method that will comprehensively resolve confusions about genetic relationships of genus Dioscorea.

Methods: A comprehensive strategy using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) was firstly proposed to evaluate the chemotaxonomy of 12 species (27 taxa) from China by hierarchical cluster analysis (HCA) based on the variations of the identified metabolites.

Results: Twenty-eight secondary metabolites (mainly steroidal saponins) were identified. The MS fragmentation patterns of DA (a new acetylated steroidal saponin at C-7 position) were firstly reported. Moreover, eight major steroidal saponins were further quantified simultaneously by UPLC-QTOF-MS method. According to HCA results, D. bulbifera L. was distinguished with species of sect. Stenophora Uline for pennogenin-type steroidal saponins. Dioscorea zingiberensis exhibited far distance from other members of sect. Stenophora Uline for two unique saponins. Dioscorea banzhuana may be reclassified into sect. Stenophora. Dioscorea nipponica subsp. rosthornii and D. collettii var. hypoglauca might be separated from their original subspecies/varieties as new species, respectively.

Conclusion: The chemotaxonomic method was successfully applied in the study of genetic relationships of Dioscorea species. This study not only enhanced the understanding of chemical constituents, but also laid basic theoretical foundations for the rational utilisation and chemotaxonomy of genus Dioscorea.
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http://dx.doi.org/10.1002/pca.2876DOI Listing
March 2020

Effect of digestion on the phenolic content and antioxidant activity of celery leaf and the antioxidant mechanism via Nrf2/HO-1 signaling pathways against Dexamethasone.

J Food Biochem 2019 07 17;43(7):e12875. Epub 2019 May 17.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.

The effect of digestion on the phenolic compounds and antioxidant activity of celery leaf were performed. In this work, 13 phenolic chemicals were discriminated by HPLC-MS, and content of phenolic and the antioxidant capacity were evaluated after digestion in vitro. After digestion, the content of phenols and flavonoids were increased by about 3-6-folds correlated with the average antioxidant activity (p < 0.05). It was found that the extraction of celery leaf (ET) decreased lipid peroxidation (MDA) and reactive oxygen species (ROS) level, and elevated the antioxidant activities of the liver, spleen, and thymus in Dexamethasone (Dex)-treated KM mice. Furthermore, ET increased the protein transcription of NF-E2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1) and glutathione s-transferase (GST) to against oxidation. These results suggested that ET can protect animals through the Nrf2/HO-1 signaling pathway from oxidative damage included by Dex. PRACTICAL APPLICATIONS: Celery is a daily edible vegetable with more pharmacological research focused on dietary fiber, yet fewer studies on the biological activity of small molecules, especially that in leaves. This study shows that the phenolic compounds from celery leaf have a distinct enhancement of oxidation after digestion in vitro, and the celery leaf reduces oxidative stress induced by Dex via Nrf2/HO-1 signaling pathway, indicating celery leaf or other food rich in phenolic compounds can be good source of functional food to fully use to promote the economic value. Moreover, it also provides theoretical information of celery leaf on digestion, which insinuates that food or Chinese medicine containing flavonoids, such as glycoside of apigenin or luteolin, have the similar digestion pattern, providing theoretical basis for later metabolism. Therefore, the absorption and metabolism of ET or flavonoids after digestion in body and the upstream signaling pathway activating Nrf2/HO-1, like PI3K or JNK phosphorylation, or downstream signaling pathway need further research.
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http://dx.doi.org/10.1111/jfbc.12875DOI Listing
July 2019

Induction of signal molecules and expression of functional genes after Pichia pastoris stimulation in Glycyrrhiza uralensis Fisch adventitious roots.

J Food Biochem 2019 04 7;43(4):e12798. Epub 2019 Feb 7.

Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, People's Republic of China.

Glycyrrhiza uralensis Fisch is threatened by over-development and consumption, and therefore, in urgent need of protection. Elicitation is considered to be an effective strategy to enhance the secondary metabolites in plant cell and organ cultures. Secondary metabolite, signal molecules, and gene expression in adventitious roots were studied by HPLC-ESI-MS , commercially available kits and qRT-PCR method, respectively. In the present study, with the addition of linolenic acid, linoleic acid, and Pichia pastoris, the highest concentration of metabolites was achieved by P. pastoris treatment. The contents of total flavonoids (7.16 mg/g) and polysaccharide (149.76 mg/g) peaked at 100 mg/L of P. pastoris, which increased by 3.09-fold and 3.28-fold compared with the control, respectively. However, the highest concentration of glycyrrhizic acid (0.62 mg/g) and glycyrrhetinic acid (0.29 mg/g) were obtained in 200 mg/L of P. pastoris and which were 3.89-fold and 2.42-fold more than the control group, respectively. ESI-MS analysis indicated that licoricesaponine B2, licoricesapoine G2, licoricesaponine J2, ononin, uralenin, gancaonin C were only identified in the P. pastoris treatment group. Furthermore, P. pastoris also enhanced accumulation of salicylic acid, jasmonic acid, nitric oxide and activities of antioxidant enzymes involved in the plant defense response. In addition, the transcriptional activity of genes involved in glycyrrhizic acid biosynthesis was significantly increased under the treatment of P. pastoris. The results provided a scientific evidence for the further exploitation of G. uralensis adventitious roots and clinical medication. PRACTICAL APPLICATIONS: This study provided an effective strategy to enhance metabolites by Pichia pastoris treatment in adventitious roots of G. uralensis. The data provide a scientific evidence for the further exploitation of G. uralensis adventitious roots and clinical medication.
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http://dx.doi.org/10.1111/jfbc.12798DOI Listing
April 2019

Effect of temperature on morphology, ginsenosides biosynthesis, functional genes, and transcriptional factors expression in Panax ginseng adventitious roots.

J Food Biochem 2019 04 1;43(4):e12794. Epub 2019 Feb 1.

Key Laboratory of Systems Bioengineering, Ministry of Education, Tianjin University, Tianjin, China.

This study researched the effect of temperature on growth and ginsenosides accumulation in adventitious root cultures of Panax ginseng. Results showed that the ginseng adventitious roots growth and differentiation ability could be affected faced with different incubation temperatures (15, 20, 25, and 30°C for 35 days). Besides, the research also demonstrated that low-temperature stimulation could promote the accumulation of ginsenosides and the content of total ginsenosides increased by 2.53 times at 10°C-7d (10°C for 7 days and then transferred to 25°C for 28 days) compared with that at 25°C. Moreover, the transcriptional levels of functional genes and PgWRKYs were analyzed by this study and the correlation analysis showed that GPS, SS, CYP716A47, CYP716A53v2, UGT74AE2, UGT94Q2, PgWRKY1, PgWRKY3, and PgWRKY8 were significantly correlated with total ginsenosides content. Furthermore, HPLC-ESI-MS analyzed that Malonyl-Rb only existed in 10°C-7d group. PRACTICAL APPLICATIONS: The survey showed that after a certain time of stimulating P. ginseng adventitious roots at low temperature, the accumulation of ginsenosides could be enhanced as their expression of related genes were regulated. It provides a theoretical foundation for the mass production of ginsenosides by controlling the temperature conditions of P. ginseng adventitious roots.
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http://dx.doi.org/10.1111/jfbc.12794DOI Listing
April 2019

Comparative effectiveness of different forms of traditional Chinese medicine for treatment of post-stroke depression: Protocol for network meta-analysis of randomized controlled trials.

Medicine (Baltimore) 2019 Jul;98(30):e16477

College of Health Science and Engineering, Tianjin University of Traditional Chinese Medicine, Healthy Industrial Park, Jinghai.

Background: Traditional Chinese medicine (TCM) therapy is effective for post-stroke depression (PSD). TCM therapy encompasses various forms of practices. However, the comparative effectiveness of these therapies is still not clear. Here, we provide a network meta-analysis protocol to compare the effects of different types of TCM therapy on PSD, using both direct and indirect evidence.

Methods: Twelve databases investigation will be conducted through the keywords from their inception to June 1, 2019. At least 2 independent reviewers will identify eligible articles. EndNote X7 software is utilized to manage the literatures and RevMan V.5.3 (The Cochrane Collaboration) software is for data processing throughout the review. The package "netmeta" (version 0.5-0) in R (version 3.0.2, The R Foundation for Statistical Computing) will be used to perform network meta-analysis (NMA). In addition, the overall quality of evidence is evaluated by GRADEPro software, and Cochrane Collaboration Risk of Bias Tool is employed for the methodological quality. Generally speaking, this review protocol is reported according to the preferred reporting items for systematic review and meta-analysis protocols 2015 guidelines.

Results: According to this protocol, it will provide evidence in support of, or against, the hypothesis that TCM therapy for PSD is more effective than pharmacotherapy. The results of this study will also provide evidence on relative efficacy of different forms of TCM. Furthermore, this analysis will show which form(s) of TCM therapy is (are) the most effective.

Conclusion: The results will help PSD doctors and patients choose the treatment regimen which is effective, time-saving and economical.

Prospero Registration Number: CRD42016041594.
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http://dx.doi.org/10.1097/MD.0000000000016477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709183PMC
July 2019

Design, synthesis, and evaluation of phosphorescent Ir(III) complexes with anticancer activity.

J Inorg Biochem 2019 08 4;197:110703. Epub 2019 May 4.

Institute of Anticancer Agents Development and Theranostic Application, The Key Laboratory of Life-Organic Analysis and Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, Department of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, China.

A range of phosphorescent Ir(III) complexes containing four diverse P^P-chelating ligands of the type [Ir(ppy)(L)][PF], (ppy = 2‑phenylpyridine) where L is 1,2‑bis(diphenylphosphino)benzene (L1), 1,2‑bis(diphenylphosphino)ethane (L2), 1,2‑bis(diphenylphosphino)propane(L3) and 1,8‑bis(diphenylphosphino)naphthalene (L4) were synthesized respectively. The iridium complexes possessed excellent antiproliferative properties, which was a substantial improvement over cisplatin, especially complex Ir1. Generally, the order of in vitro antiproliferative activity of the complexes is Ir1 > Ir2 = Ir3 > Ir4 > CDDP (Cisplatin). Two X-ray crystal structures were determined. The best complex, Ir1, was chosen to further study the mechanism of action. The self-luminescence of complex Ir1 was also successfully used to elucidate the subcellular localization. Complex Ir1 was specifically targeted to lysosomes in A549 cancer cells. This targeting caused lysosomal damage and the induction of ROS (reactive oxygen species) production in cancer cells. Flow cytometry studies confirmed that this complex induced apoptosis, especially late apoptosis. Our results suggested that changes in the mitochondrial membrane potential were responsible for apoptosis. The chemistry and biological studies showed that this class of metal complexes is worthy of further exploration to design novel anticancer drugs.
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http://dx.doi.org/10.1016/j.jinorgbio.2019.110703DOI Listing
August 2019

Spasmolytic activity of Aquilariae Lignum Resinatum extract on gastrointestinal motility involves muscarinic receptors, calcium channels and NO release.

Pharm Biol 2018 Dec;56(1):559-566

b School of Pharmaceutical Science and Technology , Tianjin University , Tianjin , China.

Context: Aquilariae Lignum Resinatum (ALR), the dry rhizome of Aquilaria agallocha R. (Thymelaeaeeae), has been widely used to treat emesis, stomachache and gastrointestinal dysfunction.

Objective: This study evaluates the effects of ALR methanol extract on gastrointestinal motility (GIM) and possible mechanisms of the action involved.

Materials And Methods: In vivo, the study evaluated the effects of ALR (200-800 mg/kg) on gastric emptying and small intestinal motility in normal and neostigmine-induced adult KM mice. The in vitro effects of ALR (0.2-1.6 mg/mL) on GIM were performed on isolated jejunum of Wistar rats, pretreated with acetylcholine (ACh), KCl, CaCl, and pre-incubation with l-NAME (a selective inhibitor of the nitric oxide synthase).

Results: In vivo, ALR (800 mg/kg) decreased gastric emptying (70.82 ± 9.81%, p < 0.01, compared with neostigmine group 91.40 ± 7.81%), small intestinal transit (42.82 ± 3.82%, p < 0.01, compared with neostigmine group 85.53 ± 5.57%). In vitro, ALR concentration dependently decreased the contractions induced by ACh (10 M) and KCl (60 mM) with respective EC values of 0.35 and 0.32 mg/mL. The Ca concentration-response curves were shifted by ALR to the right, similar to that caused by verapamil (the positive). The spasmolytic activity of ALR was inhibited by pre-incubation with l-NAME.

Discussion And Conclusions: ALR played a spasmolytic role in GIM, which is probably mediated through inhibition of muscarinic receptors, blockade of Ca influx and NO release. This is the first study presenting a comprehensive description of the effects of ALR on GIM.
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http://dx.doi.org/10.1080/13880209.2018.1492000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292371PMC
December 2018

Screening and evaluation of adventitious root lines of Panax notoginseng by morphology, gene expression, and metabolite profiles.

Appl Microbiol Biotechnol 2019 Jun 19;103(11):4405-4415. Epub 2019 Apr 19.

Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China.

Panax notoginseng is a commonly used Traditional Chinese Medicine (TCM) and has diverse pharmacological activities with triterpenoid saponins as its main active ingredient. In the cultivation of P. notoginseng, continuous cropping is a serious problem, which could induce reduced productivity, low tuber quality, and plant mortality. With unique advantages of easy control, relative stability, high yields, tissue culture is widely used in the protection of TCM resources. In this study, we screened one adventitious root line, multi-branched (MB) root induced from wild-type roots of P. notoginseng, with a high yield of total triterpenoid saponins (17.92 mg/g). The morphology analysis showed that MB root had structure similar to that of wild-type roots, except for the highly branched phenotype. MB root also showed close gene expression levels and metabolite profiles, which were also similar to those of wild-type roots of Demonstration Park (S3Y). Pearson's correlation coefficient analysis confirmed the importance of key gene, 3-hydroxy-3-methylglutaryl CoA reductase (HMGR), and transcription factor, PnERF1, in regulating triterpenoid saponin biosynthesis in P. notoginseng. These results suggested that MB root possesses potential value in the large-scale cultivation of P. notoginseng.
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http://dx.doi.org/10.1007/s00253-019-09778-zDOI Listing
June 2019

Purification, characterization and immunomodulatory activity of fructans from Polygonatum odoratum and P. cyrtonema.

Carbohydr Polym 2019 Jun 8;214:44-52. Epub 2019 Mar 8.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300193, China. Electronic address:

Two neutral polysaccharides named POP-1 and PCP-1 were purified from Polygonatum odoratum and P. cyrtonema, respectively. Results showed that both of them were composed of fructose and glucose, and the average molecular weights of them were about 5 kDa. FT-IR, 1D- and 2D-NMR analyses revealed that both POP-1 and PCP-1 contained a (2→1)-linked β-d-fructofuranose (Fruf) backbone and (2→6)-linked β-d-Fruf side chains with an internal α-d-glucopyranose (Glcp) in neokestose form. The difference between these two purified polysaccharides were that PCP-1 possessed of an acetyl group attached at O-3 of α-d-Glcp residue. In addition, PCP-1 exhibited a little better immune stimulating activity than POP-1 on cell viability and IL-6 production of RAW 264.7 macrophages. These results indicated that the acetyl group might affect the immunoregulatory activity and PCP-1 have more potential to be explored as an immunomodulatory agent.
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http://dx.doi.org/10.1016/j.carbpol.2019.03.014DOI Listing
June 2019