Publications by authors named "Xu Pang"

75 Publications

Phenolic compounds from the leaves of Crataegus pinnatifida Bge. var. major N.E.Br. and their lipid-lowering effects.

Bioorg Med Chem Lett 2021 Jun 19:128211. Epub 2021 Jun 19.

Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China. Electronic address:

A phytochemical study on the leaves of Crataegus pinnatifida Bge. var. major N.E.Br. was carried out, which finally led to the isolation of nineteen phenolic compounds (1-19). The structures of all compounds were established mainly by NMR and MS spectroscopic analysis as well as the necessary ECD experimental evidence, of which compounds 1-4 (crataegunins A-D) were identified as new phenylpropanoid-substituted epicatechins. HepG2 cells were induced by oleic acid and palmitic acid to establish the model of lipid metabolism disorder. All isolated compounds were used to intervene in the model, and the contents of triglyceride (TG) and total cholesterol (TC) were detected. Compound 2 could significantly reduce the content of TG, while compounds 2 and 11 both have good activity in reducing TC content.
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http://dx.doi.org/10.1016/j.bmcl.2021.128211DOI Listing
June 2021

Individual variation in metabolic rate, locomotion capacity and hypoxia tolerance and their relationships in juveniles of three freshwater fish species.

J Comp Physiol B 2021 Jun 6. Epub 2021 Jun 6.

Laboratory of Evolutionary Physiology and Behaviour, Chongqing Normal University, Chongqing, 401331, China.

Individual variations in metabolic rate, locomotion capacity and hypoxia tolerance and their relationships were investigated in three cyprinid species [crucian carp (Carassius auratus), common carp (Cyprinus carpio) and qingbo (Spinibarbus sinensis), in 60 individuals of each species]. Either the active metabolic rate (AMR) and critical swimming speed (U) (30 individuals) or critical oxygen tension (P) and loss of equilibrium (LOE) (30 individuals) were measured in each species after measuring the resting metabolic rate (RMR). Both the AMR and U were found to be significantly and positively correlated with the RMR in all three cyprinid species, indicating that high-RMR individuals have high aerobic capacity and thus good swimming performance. P was positively correlated with the RMR in all three species, whereas the LOE was highly positively correlated, weakly positively correlated and not correlated with the RMR in qingbo, common carp and crucian carp, respectively, possibly due to specialized morphological and biochemical adaptations involved in hypoxia tolerance in crucian and common carp. Crucian carp showed relatively poor swimming performance, i.e., a low U (relatively high variation), strong hypoxia tolerance, and low LOE (relatively low variation); qingbo showed relatively good swimming performance (relatively low variation) and weak hypoxia tolerance (relatively high variation); and common carp showed moderate swimming performance and relatively strong hypoxia tolerance (moderate variation). These interspecific differences may be due to the different lifestyles of these cyprinid fishes based on their associated fast-slow-flow regime and are outcomes of long-term selection.
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http://dx.doi.org/10.1007/s00360-021-01382-wDOI Listing
June 2021

Effects of acclimation temperature regime on the thermal tolerance, growth performance and gene expression of a cold-water fish, Schizothorax prenanti.

J Therm Biol 2021 May 2;98:102918. Epub 2021 Apr 2.

Institute of Three Gorges Ecological Fisheries of Chongqing, College of Fisheries, Southwest University, Chongqing, 400715, China; Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, Southwest University, Chongqing, 400715, China. Electronic address:

Acclimation temperature is crucial for the optimization of a condition in aquaculture; we experimentally investigated the effects of temperature acclimation on the thermal tolerance, growth performance and gene expression levels of heat shock proteins (hsp70), growth hormone (gh) and insulin-like growth factors (igf-1) in Schizothorax prenanti, a cold-water fish in the Yangtze River basin. Critical thermal maximum (CT), critical thermal minimum (CT), lethal thermal maximum (LT), lethal thermal minimum (LT), feeding intake (FI), feeding efficiency (FE), and specific growth rate (SGR) were assessed at three stable temperatures (17, 22 and 27 °C) and one variable temperature (22 ± 5 °C) for 28 d. Better growth performance was observed under variable treatment compared to stable treatments. However, fish under the 27 °C treatment exhibited much weaker growth performance than those in the 17 °C treatment. Fish under variation temperature treatment fed like those under 22 °C treatment; the fish exhibited similar SGR but a higher gh and hsp70 level under variation temperature treatment. This may be due in part to a trade-off energy expenditure to deal with the temperature fluctuation. Together, these findings suggest that juvenile Schizothorax prenanti are resilient to daily fluctuations within the temperature tested here.
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http://dx.doi.org/10.1016/j.jtherbio.2021.102918DOI Listing
May 2021

Lycium barbarum mitigates radiation injury via regulation of the immune function, gut microbiota, and related metabolites.

Biomed Pharmacother 2021 Jul 3;139:111654. Epub 2021 May 3.

Tianjin University of Traditional Chinese Medicine, Tianjin, China; Beijing Institute of Radiation Medicine, Beijing, China. Electronic address:

Previous studies have suggested that Lycium barbarum (L. barbarum) has a radioprotective function, although more in-depth investigation is still required. We investigated the radioprotective efficacy of extract of the fruits of L. barbarum (LBE) and its radioprotective mechanisms. Mice were exposed to 8.5 Gy, 5.5 Gy, or 6.0 Gy total body irradiation (TBI), and the survival rate, lymphocyte percentage, amount of cytokines, and viability of the irradiated cells, as well as the gut microbiome and fecal metabolomics were studied. LBE enhanced the survival of the mice exposed to 8.5 Gy γ-ray TBI or 5.5 Gy X-ray TBI. After 6.0 Gy γ-ray TBI, LBE exhibited good immunomodulatory properties, mainly characterized by the accelerated recovery of lymphocyte percentages, and the enhanced expression of immune-related cytokines. LBE reconstituted the gut microbiota of irradiated mice, increased the relative abundance of potentially beneficial genera (e.g., Turicibacter, Akkermansia), and decreased the relative abundance of potentially harmful bacterial genera (e.g., Rikenellaceae_RC9_gut_group). Beneficial regulatory effects of LBE on the host metabolites were also noted, and the major upregulated metabolites induced by LBE, such as Tetrahydrofolic acid and N-ornithyl-L-taurine, were positively correlated with the immune factor interleukin (IL)-6. In vitro, LBE also increased the vitality of rat small intestinal epithelial cells (IEC-6) after 4.0 Gy γ-ray irradiation and promoted the growth of Akkermansia muciniphila. These results confirmed a radioprotective function of LBE and indicated that the radioprotective mechanism may be due to immunomodulation and the synergistically modulating effect on the gut microbiota and related metabolites.
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http://dx.doi.org/10.1016/j.biopha.2021.111654DOI Listing
July 2021

Multiple component-pharmacokinetic studies on 10 bioactive constituents of Peiyuan Tongnao capsule using parallel reaction monitoring mode.

Biomed Chromatogr 2021 Apr 30:e5153. Epub 2021 Apr 30.

State Key Laboratory of Component-Based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Peiyuan Tongnao capsule (PTC) plays an important role in clinical application due to its excellent curative efficacy in the treatment of ischemic stroke and chronic cerebral circulation insufficiency. To standardize and rationalize the clinical application of PTC, a rapid and sensitive method based on ultra-high performance liquid chromatography/quadrupole-Orbitrap mass spectrometry with parallel reaction monitoring (PRM) mode was developed and validated for the pharmacokinetic (PK) study. Ten bioactive compounds (aucubin, salidroside, echinacoside, paeoniflorin, verbascoside, liquiritin, 2,3,5,4'-tetrahydroxy stilbene-2-O-β-d-glucoside, coumarin, glycyrrhizic acid, and emodin) were simultaneously determined in rat plasma. All calibration curves exhibited good linearity (r  > 0.99). The lower limits of quantification were 0.082-13.291 ng mL . The intra- and inter-day precision was 0.54-12.36%, whereas the intra- and inter-day accuracy ranged from 100.45 to 114.00%. The mean extraction recoveries were 81.77-117.66%, and the average matrix effects (MEs) were 86.23-109.96%. The high extraction recoveries and acceptable MEs indicated that the pretreatment method was feasible. And the stability was acceptable under various storage conditions and processing procedures. The validated method was successfully applied to the multiple components-PK studies, which lay the foundation for further pharmacological and clinical research of PTC and may provide a reference for other traditional Chinese medicines.
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http://dx.doi.org/10.1002/bmc.5153DOI Listing
April 2021

Screening and Selection of a New Medium for Diosgenin Production via Microbial Biocatalysis of sp.

Pharmaceuticals (Basel) 2021 Apr 21;14(5). Epub 2021 Apr 21.

Division for Medicinal Microorganisms Related Strains, CAMS Collection Center of Pathogenic Microorganisms, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

Steroidal saponins are widely used as starting precursors and medical intermediates for the semi-/total-synthesis of hundreds of steroidal drugs. One such steroidal saponin is diosgenin, which has attracted significant attention due to the huge market demand in the pharmaceutical industry. Due to water waste and severe environmental pollution, the traditional diosgenin production process based on direct acid hydrolysis is no longer used. In this study, to develop a submerged fermentation (SmF) medium for clean diosgenin production via efficient microbial biocatalysis, the Box-Behnken design (BBD) in combination with the Plackett-Burman design (PBD) was used to determine the medium compositions for strains. Three components (wheat bran, phosphate, and Tween-80) were determined as significant factors by the PBD. Using the BBD, the three significant factors were further optimized, and the optimum values were determined for maximal diosgenin production. With 21.16 g/L of wheat bran, 9.60 g/L of phosphate, and 1.97 g/L of Tween-80, the diosgenin yield was 2.28%, i.e., 3.17 mg/L/h. The experimental values agreed with the predicted values, representing a significant increase in diosgenin production compared to its production using the basic SmF medium. For the first time, we reported the development of a new medium for strains to produce diosgenin via microbial biocatalysis of the root of C. H. Wright (DZW). A simple-composition, low-cost, and high-efficiency medium was developed for the first time for the SmF of strains. The medium is considered useful for large-scale SmF and may be applicable to other fungi. This study lays a solid foundation for diosgenin production in an acid-free and wastewater-free way. It may also provide fundamental support for producing other value-added products via microbial biocatalysis of low-value materials by endophytic fungi.
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http://dx.doi.org/10.3390/ph14050390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143133PMC
April 2021

Development of a New Bioprocess for Clean Diosgenin Production through Submerged Fermentation of an Endophytic Fungus.

ACS Omega 2021 Apr 31;6(14):9537-9548. Epub 2021 Mar 31.

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, 2 Nanwei Road, Beijing 100050, P. R. China.

Diosgenin is used widely to synthesize steroidal hormone drugs in the pharmaceutical industry. The conventional diosgenin production process, direct acid hydrolysis of the root of C. H. Wright (DZW), causes large amounts of wastewater and severe environmental pollution. To develop a clean and effective method, the endophytic fungus sp. CPCC 400226 was screened for the first time for the microbial biotransformation of DZW in submerged fermentation (SmF). Statistical design and response surface methodology (RSM) were implemented to develop the diosgenin production process using the strains. The environmental variables that significantly affected diosgenin yield were determined by the two-level Plackett-Burman design (PBD) with nine factors. PBD indicates that the fermentation period, culture temperature, and antifoam reagent addition are the most influential variables. These three variables were further optimized using the response surface design (RSD). A quadratic model was then built by the central composite design (CCD) to study the impact of interaction and quadratic effect on diosgenin yield. The values of the coefficient of determination for the PBD and CCD models were all over 0.95. -values for both models were 0.0024 and <0.001, with -values of ∼414 and ∼2215, respectively. The predicted results showed that a maximum diosgenin yield of 2.22% could be obtained with a fermentation period of 11.89 days, a culture temperature of 30.17 °C, and an antifoam reagent addition of 0.20%. The experimental value was 2.24%, which was in great agreement with predicted value. As a result, over 80% of the steroidal saponins in DZW were converted into diosgenin, presenting a ∼3-fold increase in diosgenin yield. For the first time, we report the SmF of a strain used to produce diosgenin through the microbial biotransformation of DZW. A practical diosgenin production process was established for the first time for strains. This bioprocess is acid-free and wastewater-free, providing a promising environmentally friendly alternative to diosgenin production in industrial applications. The information provided in the current study may be applicable to produce diosgenin in SmF by other endophytic fungi and lays a solid foundation for endophytic fungi to produce natural products.
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http://dx.doi.org/10.1021/acsomega.1c00010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047649PMC
April 2021

Comprehensive Investigation on Ginsenosides in Different Parts of a Garden-Cultivated Ginseng Root and Rhizome.

Molecules 2021 Mar 18;26(6). Epub 2021 Mar 18.

Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing 100850, China.

Background: Ginseng is widely used as herb or food. Different parts of ginseng have diverse usages. However, the comprehensive analysis on the ginsenosides in different parts of ginseng root is scarce.

Methods: An ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) combined with UNIFI informatics platform and ultra-high-performance liquid chromatography-charged aerosol detection (UHPLC-CAD) were employed to evaluate the different parts of cultivated ginseng root.

Results: 105 ginsenosides including 16 new compounds were identified or tentatively characterized. 22 potential chemical markers were identified, 20, 17, and 19 for main root (MR) and fibrous root (FR), main root (MR) and branch root (BR), and main root (MR) and rhizome (RH), respectively. The relative contents of Re, Rb, 20(R)-Rh, Rd, and Rf were highest in FR. The relative content of Rg was highest in RH. The total relative content of pharmacopoeia indicators Rg, Re, and Rb was highest in FR.

Conclusion: The differences among these parts were the compositions and relative contents of ginsenosides. Under our research conditions, the peak area ratio of Rg and Re could distinguish the MR and FR samples. Fibrous roots showed rich ingredients and high ginsenosides contents which should be further utilized.
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http://dx.doi.org/10.3390/molecules26061696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003075PMC
March 2021

Wide-scope multi-residue analysis of pesticides in beef by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Food Chem 2021 Jul 20;351:129345. Epub 2021 Feb 20.

Key Laboratory of Agro-food Safety and Quality of Ministry of Agriculture and Rural Affairs, Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China. Electronic address:

Increasing pesticide contamination in foods of animal origin has made the wide-scope multi-residue analysis of pesticides an international concern. In this study, a sensitive and reliable multi-residue pesticide analysis method for beef was developed with the use of 129 pesticides to demonstrate the full scope of the method. The pesticides were extracted and purified using a modified QuEChERS technique and analysed using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. An orthogonal array design was employed for optimisation of the method, significantly scientising and simplifying the process. Method validation revealed satisfactory sensitivity with limits of quantification values ranging from 0.003 to 11.37 µg∙kg. Matrix effects ranged from 83.85% to 120.66%. Recovery at three spiking levels (20, 50, and 100 µg∙kg) were 70.51-128.12% and the intra-day and inter-day precisions were less than 20%, indicating good accuracy and precision.
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http://dx.doi.org/10.1016/j.foodchem.2021.129345DOI Listing
July 2021

Changes of matrix metalloproteinases in the stroma after corneal cross-linking in rabbits.

Int J Ophthalmol 2021 18;14(1):26-31. Epub 2021 Jan 18.

Department of Ophthalmology, the Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China.

Aim: To observe changes in the content of matrix metalloproteinases (MMPs) in the corneal stroma after corneal cross-linking (CXL) in rabbits, and further explore the corneal pathophysiological process after CXL.

Methods: Forty-two rabbits (42 eyes) were randomly divided into seven groups. One group served as the control group, while the other six groups were treated with CXL. The concentrations of MMPs in corneal stroma were evaluated through parallel reaction monitoring at baseline and 3, 7, 15, 30, 90, and 180d after treatment.

Results: The levels of MMP-2 in the corneal stroma of rabbits were 0.76±0.07, 2.78±1.39, 4.12±0.69, 2.00±0.29, 2.00±0.30, 1.22±0.18, and 1.35±0.18 (10 mol/g) at baseline and 3, 7, 15, 30, 90, and 180d after treatment, respectively. The contents of tissue inhibitor of metalloproteinase-1 (TIMP-1) were 1.83±0.26, 7.94±0.58, 6.95±2.64, 3.81±0.48, 3.07±0.92, 1.72±0.19, and 1.69±0.74 (10 mol/g), respectively. The ratios of MMP-2/TIMP-1 were 0.42±0.33, 0.36±0.20, 0.62±0.10, 0.54±0.15, 0.68±0.13, 0.71±0.10, and 0.68±0.09, respectively. After CXL, the expression of MMP-2 and TIMP-1 in the rabbit corneal stroma was initially increased and subsequently decreased. The levels of MMP-2 remained higher than those recorded at baseline 180d after treatment, but it was not statistically significant. The levels of TIMP-1 returned to baseline levels at 90d after treatment. The ratio of MMP-2/TIMP-1 started to rise from 7d after CXL. It was significantly higher than that calculated at baseline 30-180d after CXL. The results for MMP-1, -3, -7, -9, -13, and TIMP-2 were negative.

Conclusion: CXL can lead to changes in the content of MMP-2 and TIMP-1 in the rabbit corneal stroma. The ratio of MMP-2/TIMP-1 remains higher versus baseline, indicating that MMP-2 is involved in the corneal pathophysiological process after CXL.
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http://dx.doi.org/10.18240/ijo.2021.01.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790665PMC
January 2021

New steroidal glycosides from the roots of .

J Asian Nat Prod Res 2021 Mar 18;23(3):205-216. Epub 2021 Jan 18.

Beijing Institute of Radiation Medicine, Beijing 100850, China.

Steroidal saponins were the main active constituents of the traditional medicinal herb . A phytochemical investigation of roots led to the isolation of nine new steroidal glycosides () and seven known analogues (-). Their structures were established by spectroscopic analyses as well as necessary chemical evidence.
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http://dx.doi.org/10.1080/10286020.2021.1873956DOI Listing
March 2021

HTBPI, an active phenanthroindolizidine alkaloid, inhibits liver tumorigenesis by targeting Akt.

FASEB J 2020 09 24;34(9):12255-12268. Epub 2020 Jul 24.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Akt, a crucial protein involved in a variety of signaling pathways in cancer, acts as an important regulator of survival in hepatocellular carcinoma (HCC), and provides curative option for the related drugs development. We have found an active phenanthroindolizidine alkaloid, (13aR,14R)-9,11,12,13,13a,14-hexahydro-3,6,7-trimethoxydibenzo[f,h]pyrrolo[1,2-b]isoquinolin-14-ol (HTBPI), is a promising Akt inhibitor effective in the suppression of HCC cells proliferation through stimulating apoptotic and autophagic capability in vivo and in vitro. Treatment of HTBPI combined with a classical autophagy-lysosomal inhibitor (bafilomycin A1), could enhance stimulation effects of apoptosis on HCC cell lines. In addition, we confirmed HTBPI targeting Akt, occupied the kinase binding domain (Thr 308) of Akt to inactivate its function by CETSA and DARTS assay. In contrast, ectopic Akt-induced overexpression significantly abrogated inhibitory effects of HTBPI on cell viability and proliferation. Furthermore, high p-Akt (Thr 308) expression is collated with liver tumor formation and poor survival in HCC patients. In conclusions, HTBPI impeded HCC progress through regulation of apoptosis and autophagy machinery via interaction with p-Akt (Thr 308). This may provide potential molecular candidate by targeting Akt for the therapy of HCC patients.
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http://dx.doi.org/10.1096/fj.202000254RDOI Listing
September 2020

Anemarrhena asphodeloides modulates gut microbiota and restores pancreatic function in diabetic rats.

Biomed Pharmacother 2021 Jan 29;133:110954. Epub 2020 Nov 29.

Beijing Institute of Radiation Medicine, Beijing, China. Electronic address:

Anemarrhena asphodeloides is an herb widely used to treat symptoms associated with diabetes in traditional Chinese medicine. However, its key components and metabolites have low bioavailability and poor host absorption. To clarify the anti-diabetic mechanism of A. asphodeloides extract (AAE), we examined the anti-diabetic effects of AAE in rats with diabetes induced by a high-fat diet and streptozotocin. Faeces levels of the main components and metabolites of AAE were significantly higher than levels in plasma, which indicated that gut microbiota might play important roles in its anti-diabetic effect. Microbiological studies showed that unabsorbed components increased the diversity of the gut microbiota, enriched potentially beneficial bacteria, and suppressed potentially harmful bacteria. In vitro studies showed that AAE promoted the proliferation of Blautia coccoides, a bacterium with positive implication for diabetes, in a dose-dependent manner. AAE also promoted pancreatic cell regeneration and restored the function of pancreatic islet cells via peroxiredoxin 4 overexpression. Overall, these results suggest that AAE alleviates diabetes via modulating gut microbiota and protein expression.
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http://dx.doi.org/10.1016/j.biopha.2020.110954DOI Listing
January 2021

Development of a New High-Cell Density Fermentation Strategy for Enhanced Production of a Fungus β-Glucosidase in .

Front Microbiol 2020 21;11:1988. Epub 2020 Aug 21.

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Traditional diosgenin manufacturing process has led to serious environmental contamination and wastewater. Clean processes are needed that can alternate the diosgenin production. The β-glucosidase FBG1, cloned from sp. CPCC 400709, can biotransform trillin and produce diosgenin. In this study, production of recombinant FBG1 was implemented to investigate various conventional methanol induction strategies, mainly including DO-stat (constant induction DO), μ-stat (constant exponential feeding rate) and m-stat (constant methanol concentration). The new co-stat strategy combining μ-stat and m-stat strategies was then developed for enhanced FBG1 production during fed-batch high-cell density fermentation on methanol. The fermentation process was characterized with respect to cell growth, methanol consumption, FBG1 production and methanol metabolism. It was found that large amounts of formaldehyde were released by the enhanced dissimilation pathway when the co-stat strategy was implemented, and therefore the energy generation was enhanced because of improved methanol metabolism. Using co-stat feeding, the highest volumetric activity reached ∼89 × 10 U/L, with the maximum specific activity of ∼90 × 10 U/g. After 108 h induction, the highest volumetric production reached ∼403 mg/L, which was ∼91, 154, and 183 mg/L higher than the maximal production obtained at m-stat, μ-stat, and DO-stat strategies, respectively. FBG1 is the first produced recombinant enzyme for diosgenin production through the biotransformation of trillin. Moreover, this newly developed co-stat induction strategy represents the highest expression of FBG1 in , and the strategy can be used to produce FBG1 from similar strains harboring gene, which lays solid foundation for clean and sustainable production of diosgenin. The current work provides unique information on cell growth, substrate metabolism and protein biosynthesis for enhanced β-glucosidase production using a strain under controlled fermentation conditions. This information may be applicable for expression of similar proteins from strains.
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http://dx.doi.org/10.3389/fmicb.2020.01988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472535PMC
August 2020

Furostanol Saponins from Promote the Expansion of Human Cord Blood Hematopoietic Stem and Progenitor Cells.

J Nat Prod 2020 09 1;83(9):2567-2577. Epub 2020 Sep 1.

Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China.

is a medicinal plant known to biosynthesize steroidal saponins. A phytochemical investigation of the rhizomes of led to the isolation of nine new furostanol saponins (-) and 11 known analogues (-). Five of these new compounds were shown to have hydroxy groups at the C-5 and C-6 positions, while two possess a rare aglycone containing carbonyl groups at the C-16 and C-22 positions as well as a Δ double bond, and the others have conjugated double bonds in the E-ring or have different sugar chains at the C-3 position. All the isolates were tested for their effect on the expansion of human cord blood (CB) CD34 hematopoietic stem and progenitor cells. It was found that CB CD34 cells treated with compounds , , , , , , and showed increased numbers of rigorously phenotype-defined hematopoietic stem cells. Notably, compounds , , , and demonstrated an enhanced ability to increase the percentages and numbers of CB CD34CD38 cells and multipotential progenitors. The present study is the first to report that furostanol saponins from rhizomes can promote hematopoietic stem/progenitor cell (HSPC) expansion.
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http://dx.doi.org/10.1021/acs.jnatprod.9b01268DOI Listing
September 2020

Steroidal glycosides, homoisoflavanones and cinnamic acid derivatives from Polygonatum odoratum and their inhibitory effects against influenza A virus.

Fitoterapia 2020 Oct 26;146:104689. Epub 2020 Jul 26.

Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, People's Republic of China. Electronic address:

A phytochemical investigation of Polygonatum odoratum roots led to the isolation of fifteen steroidal glycosides (1-15), three homoisoflavanones (16-18) and four cinnamic acid derivatives (19-22). The structures of all isolated compounds were established mainly by spectroscopic analyses as well as necessary chemical evidence, of which 1-8 (polygodorasides A-G) were identified as new steroidal glycosides. Among the isolates, compounds 7 and 17 showed remarkable in vitro inhibitory effects against influenza A virus with IC values of 14.30 and 49.70 μM (positive control ribavirin 28.4 μM).
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http://dx.doi.org/10.1016/j.fitote.2020.104689DOI Listing
October 2020

Anthraquinone analogues with inhibitory activities against influenza a virus from .

J Asian Nat Prod Res 2020 Jul 2:1-7. Epub 2020 Jul 2.

Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.

Three anthraquinone analogues (-) were isolated by phytochemical work on EtOAc-soluble ingredients extracted from the roots of . The structures of all isolates were elucidated by NMR, MS and CD experiments, of which (polygodoquinone A) was identified as a new anthraquinone derivative. Specifically, represents an unusual structure composed of a naphthoquinone derivative linked to an anthraquinone via a C-C bond. - exhibited remarkable influenza A virus inhibitory activity with IC values of 11.4, 11.0, and 2.3 μM, respectively, which were better than ribavirin as the positive control.
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http://dx.doi.org/10.1080/10286020.2020.1779707DOI Listing
July 2020

Steroidal saponins from Trillium tschonoskii rhizomes and their cytotoxicity against HepG2 cells.

Steroids 2020 04 23;156:108587. Epub 2020 Jan 23.

Beijing Institute of Radiation Medicine, Beijing 100850, China. Electronic address:

A phytochemical study on the rhizomes of Trillium tschonoskii led to the isolation of fourteen new steroidal saponins, trillitschosides S1-S14 (1-14), along with ten known analogues (15-24). Their structures were established mainly by spectroscopic analyses as well as necessary chemical evidence. All isolated compounds were screened for the cytotoxicity against HepG2 cells, and the results demonstrated that only the known compounds 21-24 exhibited the remarkable cytotoxic activity against HepG2 cells which is much better than the positive control of 5-FU.
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http://dx.doi.org/10.1016/j.steroids.2020.108587DOI Listing
April 2020

Multi-residue analysis of 126 pesticides in chicken muscle by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

Food Chem 2020 Mar 12;309:125503. Epub 2019 Sep 12.

Key Laboratory of Agro-food Safety and Quality of Ministry of Agriculture and Rural Affairs, Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China. Electronic address:

Ensuring food safety requires effective methods for the simultaneous analysis of pesticide residues in animal-origin foods. A sensitive and reliable method for the multi-residue analysis of 126 pesticides in chicken muscle was developed using a modified QuEChERS technique and ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. A new enhanced matrix removal-lipid material was used as the QuEChERS dispersive purification adsorbent. Method validation revealed satisfactory linearities with correlation coefficients higher than 0.994 for all pesticides. All limits of quantification were below 10 µg/kg, except in the cases of oxadiazon, clomazone, and lactofen. The matrix effects were nearly negligible, ranging from 73.09% to 125.22%. The recoveries at three spiked levels (50, 100, and 200 μg/kg) were 71.38-120.43% and the intra-day and inter-day precisions were lower than 10%, indicating the good accuracy and precision of the established method.
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http://dx.doi.org/10.1016/j.foodchem.2019.125503DOI Listing
March 2020

[N-containing compounds from seeds of Paganum harmala].

Zhongguo Zhong Yao Za Zhi 2019 Apr;44(8):1601-1606

Research Institute of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine Tianjin 300193,China.

To investigate the N-containing compounds in the seeds of Paganum harmala,fourteen compounds were finally isolated from the 95% Et OH extract of P. harmala seeds by using various chromatographic techniques including silica gel,MCI resin,and ODS column chromatography as well as the semi-preparative HPLC. Depending on spectroscopic techniques and comparison with the reported data in the literatures,the structures of all compounds were identified as N-[3-(2-amino-4-methoxyphenyl)-3-oxopropyl]acetamide(1),dehydroharmalacidine(2),harmalacidine(3),harmine N-oxide(4),harmine(5),tetrahydroharmine(6),demethylharmalacidine(7),harmol(8),tetrahydroharmol(9),harmindol β-D-glucopyranoside(10),tryptophyl β-D-glucopyranoside(11),pegamineβ-D-glucopyranoside(12),vasicol(13) and vasicinone(14). Among them,1 was a new compound,and 2 and 10 were obtained as natural products for the first time.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20190118.009DOI Listing
April 2019

7-Deoxynarciclasine shows promising antitumor efficacy by targeting Akt against hepatocellular carcinoma.

Int J Cancer 2019 12 23;145(12):3334-3346. Epub 2019 May 23.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Akt is a promising therapeutic target for cancer treatment. In our study, we have identified that 7-deoxynarciclasine (7-DONCS) is a potential inhibitor of Akt, which results in the repression of multiple oncogenic processes in hepatocellular carcinoma (HCC). We have found that 7-DONCS suppresses the growth of HCC by inducing the apoptotic and autophagic capacities, as well as by inhibiting epithelial-mesenchymal transition (EMT) in vitro and in vivo. Pretreatment of cells with specific autophagy inhibitor (Bafilomycin A1) or knockdown of endogenous LC‐3B by siRNA strongly enhences 7‐DONCS‐regulated apoptosis and EMT. Consequently, we have found that 7-DONCS selectively inhibits phospho-Akt (Ser473), and subsequent molecular docking reveals that 7-DONCS directly binds to the C-terminal domain of Akt. Overexpressing Akt significantly blocks these effects via 7-DONCS in HCC cells. Furthermore, 7-DONCS, by targeting Akt, exhibits a promising therapeutic effect in orthotopic hepatocellular tumors. Finally, higher p-Akt expression is associated with poor prognosis, and higher level of Akt was positively correlated with the enrichment of both apoptosis and autophagy downregulation, and EMT upregulation in HCC patients. These studies suggest that 7-DONCS serves as an attractive drug candidate by targeting Akt for future HCC therapy.
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http://dx.doi.org/10.1002/ijc.32395DOI Listing
December 2019

[Chemcial constituents of Eclipta prostrata].

Zhongguo Zhong Yao Za Zhi 2018 Sep;43(17):3498-3505

School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

A total of twenty-two compounds were isolated from the 95% EtOH extract of Eclipta prostrata by various purification steps, and their structures were established as ecliptalignin A (1),ecliptasaponin Ⅰ (2), ecliptasaponin Ⅱ (3), echinocystic acid (4), 3-oxo-16α-hydroxy-olean-12-en-28-oic acid (5), acacetin-7--rutinoside (6), luteoloside (7), apigenin (8), luteolin (9), acacetin (10), skullcapflavone Ⅱ (11), kaempferol (12), kaempferide (13), quercetin (14), 4',7-dihydroxyl-3',6'-dimethoxylisoflavone-7--glucoside (15), ecliptal (16), 5-hydroxymethyl-(2,2',5',2″)-terthienyl tiglate (17), psoralen (18), isopsoralen (19), wedelolactone (20), crinumaquine (21), and 2,3,9,12-tetramethoxyprotoberberine (22) mainly based on the spectroscopic techniques, of which 1 was a new lignin analogue, and 5, 6, 10-13, 15, 18, 19, 21 and 22 were isolated form this plant for the first time.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20180625.001DOI Listing
September 2018

Lycorine Displays Potent Antitumor Efficacy in Colon Carcinoma by Targeting STAT3.

Front Pharmacol 2018 8;9:881. Epub 2018 Aug 8.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Signal transducer and activator of transcription 3 (STAT3) is an attractive therapeutic target for cancer treatment. In this study, we identify lycorine is an effective inhibitor of STAT3, leading to repression of multiple oncogenic processes in colon carcinoma. Lycorine selectively inactivates phospho-STAT3 (Tyr-705), and subsequent molecular docking uncovers that lycorine directly binds to the SH2 domain of STAT3. Consequently, we find that lycorine exhibits anti-proliferative activity and induces cell apoptosis on human colorectal cancer (CRC) . Lycorine induces the activation of the caspase-dependent mitochondrial apoptotic pathway, as indicated by activation of caspase and increase of the ratio of Bax/Bcl-2 and mitochondrial depolarization. Overexpressing STAT3 greatly blocks these effects by lycorine in CRC cells. Finally, lycorine exhibits a potential therapeutic effect in xenograft colorectal tumors by targeting STAT3 without observed toxicity. Taken together, the present study indicates that lycorine acts as a promising inhibitor of STAT3, which blocks tumorigenesis in colon carcinoma.
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http://dx.doi.org/10.3389/fphar.2018.00881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092588PMC
August 2018

Two new naphthalene glycosides from the seeds of .

J Asian Nat Prod Res 2019 Oct 27;21(10):970-976. Epub 2018 Jun 27.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine , Tianjin 300193 , China.

A phytochemical study on the seeds of was carried out, which finally led to obtain two naphthalenes ( and ), two naphthopyrans ( and ) and twelve anthraquinones (-). The structures of all compounds were established mainly by NMR and MS experiments as well as the necessary chemical evidence. Among them, and (obtusinaphthalensides A and B) were identified to be new naphthalene glycosides.
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http://dx.doi.org/10.1080/10286020.2018.1478816DOI Listing
October 2019

Magnolin promotes autophagy and cell cycle arrest via blocking LIF/Stat3/Mcl-1 axis in human colorectal cancers.

Cell Death Dis 2018 06 13;9(6):702. Epub 2018 Jun 13.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.

Magnolin is a multi-bioactive natural compound that possesses underlying anti-cancer properties. However, the mechanisms underlying remain to be elucidated. Here, we report the role of magnolin in suppressing human colorectal cancer (CRC) cells via activating autophagy and cell cycle arrest in vitro and in vivo. Pre-treatment of cells with specific autophagy inhibitor (3-methyladenine) or knockdown of endogenous LC-3B by siRNA significantly abrogates magnolin-induced cell cycle arrest. Molecular validation mechanistically shows that magnolin-induced autophagy and cell cycle arrest in CRC cells is correlated with decreased transcriptional levels of leukemia inhibitory factor (LIF), and we further find that inhibition of LIF decreases phosphorylation level of Stat3 and represses transcriptional expression of Mcl-1. Furthermore, magnolin-induced autophagy and cell cycle arrest suppress the growth of xenograft colorectal tumors without apparent toxicity. Finally, we evaluate the clinical correlation of LIF/Stat3/Mcl-1 in CRC patient tissues. As expected, LIF, p-Stat3, and Mcl-1 levels are high in CRC tissue but are scarcely found in normal colon tissue. High positive expressions of LIF or Mcl-1 are associated with poor prognosis. Doubly positive cases have shown the worst outcome. Taken together, our results have clarified a novel molecular mechanism whereby magnolin induces autophagy and cell cycle arrest through LIF/Stat3/Mcl-1 pathway in CRCs. Our results also have revealed that magnolin has a promising therapeutic potential in CRCs.
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http://dx.doi.org/10.1038/s41419-018-0660-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999973PMC
June 2018

New anthraquinone and eurotinone analogue from the seeds of and their inhibitory effects on human organic anion transporters 1 and 3.

Nat Prod Res 2019 Dec 4;33(23):3409-3416. Epub 2018 Jun 4.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine , Tianjin , China.

A continuous phytochemical study on the seeds of (Syn.: ) led to the isolation of a new anthraquinone analogue, obtusifolin-2---D-(6'--,-unsaturated butyryl)-glucopyranoside () and a new eurotinone analogue, -9-dehydroxyeurotinone--D-glucopyranoside (). Their structures were established mainly by NMR and MS experiments as well as the necessary chemical evidences. Their inhibitory effects on two organic anion transporters (OAT1 and OAT3) were investigated and the results showed that exhibited a strongly specific inhibitory effect on OAT1 at 100 μM.
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http://dx.doi.org/10.1080/14786419.2018.1480621DOI Listing
December 2019

Isolation of endophytic fungi from Dioscorea zingiberensis C. H. Wright and application for diosgenin production by solid-state fermentation.

Appl Microbiol Biotechnol 2018 Jul 3;102(13):5519-5532. Epub 2018 May 3.

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.

In this study, endophytic fungi were isolated from Dioscorea zingiberensis C.H. Wright (DZW), and a novel clean process to prepare diosgenin from DZW was developed. A total of 123 strains of endophytic fungi were isolated from different plant tissues of DZW. Among them, the strain Fusarium sp. (CPCC 400709) showed the best activity of hydrolyzing steroidal saponins in DZW into diosgenin. Thus, this strain was used to prepare diosgenin from DZW by solid-state fermentation. The fermentation parameters were optimized using response surface methodology, and a high yield of diosgenin (2.16%) was obtained at 14.5% ammonium sulfate, an inoculum size of 12.3%, and 22 days of fermentation. Furthermore, the highest diosgenin yield (2.79%) was obtained by co-fermentation with Fusarium sp. (CPCC 400709) and Curvularia lunata (CPCC 400737), which was 98.9% of that obtained by β-glucosidase pretreated acid hydrolysis (2.82%). This process is acid-free and wastewater-free, and shows promise as an effective and clean way to prepare diosgenin for use in industrial applications from DZW.
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http://dx.doi.org/10.1007/s00253-018-9030-5DOI Listing
July 2018

Secoiridoid analogues from the fruits of Ligustrum lucidum and their inhibitory activities against influenza A virus.

Bioorg Med Chem Lett 2018 05 30;28(9):1516-1519. Epub 2018 Mar 30.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Tianjin Key Laboratory of TCM Chemistry and Analysis, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. Electronic address:

A phytochemical study focusing on the secoiridoid components in the fruits of Ligustrum lucidum was carried out, which finally led to the isolation of nine secoiridoid glycosides (1-9) together with two secoiridoids (10, 11). The structures of all compounds were established mainly by NMR and MS experiments as well as the necessary chemical evidence, of which 1, 2, 4 (ligulucisides A-C), 10 and 11 (liguluciridoids A and B) were identified as new secoiridoid analogues. An in vitro antiviral bioassay indicated that 1, 4, 6, and 10 displayed the inhibitory activities against influenza A virus with the IC values of 16.5, 12.5, 13.1, and 18.5 μM, respectively, which were better than the positive control Ribavirin (IC 22.6 μM). .
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http://dx.doi.org/10.1016/j.bmcl.2018.03.080DOI Listing
May 2018

Validated UPLC-MS/MS method for quantification of seven compounds in rat plasma and tissues: Application to pharmacokinetic and tissue distribution studies in rats after oral administration of extract of Eclipta prostrata L.

Biomed Chromatogr 2018 Jun 27;32(6):e4191. Epub 2018 Feb 27.

Tianjin State Key Laboratory of Modern Chinese Medicine, Nankai District, Tianjin, People's Republic of China.

A rapid, sensitive and specific ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method was developed to investigate the pharmacokinetics and tissue distribution of Eclipta prostrata extract. Rats were orally administrated the 70% ethanol extract of E. prostrata, and their plasma as well as various organs were collected. The concentrations of seven main compounds, ecliptasaponin IV, ecliptasaponin A, apigenin, 3'-hydroxybiochanin A, luteolin, luteolin-7-O-glucoside and wedelolactone, were quantified by UPLC-MS/MS through multiple reactions monitoring method. The precisions (RSD) of the analytes were all <15.00%. The extraction recoveries ranged from 74.65 to 107.45% with RSD ≤ 15.36%. The matrix effects ranged from 78.00 to 118.06% with RSD ≤ 15.04%. To conclude, the present pharmacokinetic and tissue distribution studies provided useful information for the clinical usage of Eclipta prostrata L.
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http://dx.doi.org/10.1002/bmc.4191DOI Listing
June 2018

Prenylated flavonoids and dihydrophenanthrenes from the leaves of Epimedium brevicornu and their cytotoxicity against HepG2 cells.

Nat Prod Res 2018 Oct 26;32(19):2253-2259. Epub 2017 Nov 26.

a Tianjin State Key Laboratory of Modern Chinese Medicine , Tianjin University of Traditional Chinese Medicine , Tianjin , China.

Phytochemical study on the leaves of Epimedium brevicornu finally led to the isolation of four prenylated flavonoids (1-4) and three dihydrophenanthrenes (5-7), of which 1, 2, 5 and 7 were new compounds. The structures of these compounds were established mainly by spectroscopic techniques, including NMR spectroscopy and mass spectrometry. These isolates exhibited the cytotoxic activities against HepG2 cells with the IC values of 32.8-87.3 μM.
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http://dx.doi.org/10.1080/14786419.2017.1405410DOI Listing
October 2018