LC-MS-Based Metabolomics Reveals the Mechanism of Protection of Berberine against Indomethacin-Induced Gastric Injury in Rats.

Berberine is a natural isoquinoline alkaloid with low toxicity, which exists in a wide variety of medicinal plants. Berberine has been demonstrated to exhibit potent prevention of indomethacin-induced gastric injury (GI) but the related mechanism remains unclear. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied for the first time to investigate the alteration of serum metabolites in the protection of berberine against indomethacin-induced gastric injury in rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-GI effect of berberine. The pharmacodynamic data indicated that berberine could ameliorate gastric pathological damage, inhibit the level of proinflammatory factors in serum, and increase the level of antioxidant factors in serum. The LC-MS-based metabolomics analysis conducted in this study demonstrated the presence of 57 differential metabolites in the serum of rats with induced GI caused by indomethacin, which was associated with 29 metabolic pathways. Moreover, the study revealed that berberine showed a significant impact on the differential metabolites, with 45 differential metabolites being reported between the model group and the group treated with berberine. The differential metabolites were associated with 24 metabolic pathways, and berberine administration regulated 14 of the 57 differential metabolites, affecting 14 of the 29 metabolic pathways. The primary metabolic pathways affected were glutathione metabolism and arachidonic acid metabolism. Based on the results, it can be concluded that berberine has a gastroprotective effect on the GI. This study is particularly significant since it is the first to elucidate the mechanism of berberine's action on GI. The results suggest that berberine's action may be related to energy metabolism, oxidative stress, and inflammation regulation. These findings may pave the way for the development of new therapeutic interventions for the prevention and management of NSAID-induced GI disorders.

Multi-locus genome-wide association study and genomic prediction for flowering time in chrysanthemum.

MAIN CONCLUSION: Multi-locus GWAS detected several known and candidate genes responsible for flowering time in chrysanthemum. The associations could greatly increase the predictive ability of genome selection that accelerates the possible application of GS in chrysanthemum breeding. Timely flowering is critical for successful reproduction and determines the economic value for ornamental plants. To investigate the genetic architecture of flowering time in chrysanthemum, a multi-locus genome-wide association study (GWAS) was performed using a collection of 200 accessions and 330,710 single-nucleotide polymorphisms (SNPs) via 3VmrMLM method. Five flowering time traits including budding (FBD), visible colouring (VC), early opening (EO), full-bloom (OF) and senescing (SF) stages, plus five derived conditional traits were recorded in two environments. Extensive phenotypic variations were observed for these flowering time traits with coefficients of variation ranging from 6.42 to 38.27%, and their broad-sense heritability ranged from 71.47 to 96.78%. GWAS revealed 88 stable quantitative trait nucleotides (QTNs) and 93 QTN-by-environment interactions (QEIs) associated with flowering time traits, accounting for 0.50-8.01% and 0.30-10.42% of the phenotypic variation, respectively. Amongst the genes around these stable QTNs and QEIs, 21 and 10 were homologous to known flowering genes in Arabidopsis; 20 and 11 candidate genes were mined by combining the functional annotation and transcriptomics data, respectively, such as MYB55, FRIGIDA-like, WRKY75 and ANT. Furthermore, genomic selection (GS) was assessed using three models and seven unique marker datasets. We found the prediction accuracy (PA) using significant SNPs identified by GWAS under SVM model exhibited the best performance with PA ranging from 0.90 to 0.95. Our findings provide new insights into the dynamic genetic architecture of flowering time and the identified significant SNPs and candidate genes will accelerate the future molecular improvement of chrysanthemum.

Improved measurement of the glue layer in composite material by using sparse deconvolution.

Due to its powerful penetration, and greater spatial resolution than microwaves and ultrasonic waves, the terahertz technique stands out as being particularly useful in identifying thin glue layers in multilayered materials. However, the arrival times of echoes are challenging to pinpoint from the experimental data because of the temporal form of the incident pulse and the system noise. Here, two terahertz signal sparse deconvolution algorithms are studied to more accurately identify the times of the echoes. Using the circulant structure of the convolution matrix, the method's computation time can be lowered to hundreds of milliseconds. In addition, a method based on group velocity dispersion is investigated to reduce the impact of time-varying pulses with minimal computational expense. The presented algorithms have the potential to be employed in real-time inspection in production lines due to their quick speed and high confidence.

Application of UPLC-Triple TOF-MS/MS metabolomics strategy to reveal the dynamic changes of triterpenoid saponins during the decocting process of Asian ginseng and American ginseng.

Triterpenoid saponins are the main bioactive components contributed to the nutritional value of ginseng, and different process conditions will affect their content and quality. To study the holistic characterization and dynamic changes of triterpenoid saponins in Asian ginseng (ASG) and American ginseng (AMG) during soaking and decoction, a UPLC-Triple TOF-MS/MS-based metabolomics strategy was used to characterize and discover differential saponin markers. In total, 739 triterpenoid saponins (including 225 potential new saponins) were identified from ASG and AMG in untargeted metabolomics. Based on PCA and OPLS-DA, 51 and 48 saponin markers were screened from soaked and decocted ASG and AMG, respectively. Additionally, targeted metabolomics analysis and HCA of 22 ginsenoside markers suggested that decoction of ASG and AMG for 2 h to 4 h could significantly increase the contents of rare ginsenosides (G), such as G-Rg3, G-Rg5, G-F4. This study provides a scientific insight that high boiling combined with simmering enriches ASG and AMG extracts with rich rare ginsenosides that are more beneficial to human health.

Synthesis and biological evaluation of novel demethylzeylasteral derivatives as potential anticancer agents.

Demethylzeylasteral (DEM), a class of terpenoids isolated from natural plants, frequently exhibits moderate or limited inhibitory effect on tumor growth across multiple cancer types. Thus, here we attempted to elevate the anti-tumor efficacy of DEM by altering active groups in its chemical structure. Initially, we synthesized a series of novel DEM derivatives 1-21 through performing a series of modifications of its phenolic hydroxyl groups at C-2/3, C-4 and C-29 positions. The anti-proliferative activities of these new compounds were subsequently assessed using three human cancer cell line models (A549, HCT116 and HeLa) and CCK-8 assay. Our data showed that compared to original DEM compound, derivative 7 exhibited remarkable inhibition effect on A549 (16.73 ± 1.07 µM), HCT116 (16.26 ± 1.94 µM) and HeLa (17.07 ± 1.09 µM), almost reaching to the same level of DOX. Moreover, the structure-activity relationships (SARs) of the synthesized DEM derivatives were discussed in detail. We found that treatment with derivative 7 only led to moderate cell cycle arrest at S-phase in a concentration-dependent manner. Meanwhile, derivative 7 treatment markedly induced apoptosis in tumor cells. Consistent with this observation, our subsequent docking analysis showed that derivative 7 is capable of activating caspase-3 through interaction with the His 121 and Gly 122 residues of the enzyme. Overall, we have developed a new series of DEM derivatives with elevated anti-tumor efficacy relative to its parent form. The results suggested that derivative 7 has great potential to be employed as an anticancer agent candidate for natural product-based cancer chemotherapy.

Targeting receptor tyrosine kinases in ovarian cancer: Genomic dysregulation, clinical evaluation of inhibitors, and potential for combinatorial therapies.

Epithelial ovarian cancer (EOC) remains one of the leading causes of cancer-related deaths among women worldwide. Receptor tyrosine kinases (RTKs) have long been sought as therapeutic targets for EOC, as they are frequently hyperactivated in primary tumors and drive disease relapse, progression, and metastasis. More recently, these oncogenic drivers have been implicated in EOC response to poly(ADP-ribose) polymerase (PARP) inhibitors and epigenome-interfering agents. This evidence revives RTKs as promising targets for therapeutic intervention of EOC. This review summarizes recent studies on the role of RTKs in EOC malignancy and the use of their inhibitors for clinical treatment. Our focus is on the ERBB family, c-Met, and VEGFR, as they are linked to drug resistance and targetable using commercially available drugs. The importance of these RTKs and their inhibitors is highlighted by their impact on signal transduction and intratumoral heterogeneity in EOC and successful use as maintenance therapy in the clinic through suppression of the VEGF/VEGFR axis. Finally, the therapeutic potential of RTK inhibitors is discussed in the context of combinatorial targeting via co-inhibiting proliferative and anti-apoptotic pathways, epigenomic/transcriptional programs, and harnessing the efficacy of PARP inhibitors and programmed cell death 1/ligand 1 immune checkpoint therapies.

Retraction: Metabolomics reveals that PPARα activation protects against lithocholic acid-induced liver injury.

[This retracts the article DOI: 10.1039/C7RA08823J.].

Corylin ameliorates chronic ulcerative colitis via regulating the gut-brain axis and promoting 5-hydroxytryptophan production in the colon.

BACKGROUND: Chronic ulcerative colitis (UC) is a lifelong disease, patients with chronic UC have a high prevalence of common mental disorders. The increasing interest in the role of gut-brain axis is seen in inflammatory bowel diseases. PURPOSE: Corylin is a representative flavonoid compound isolated from the Psoraleae Fructus. This study aimed to identify the effects and mechanism of corylin on the inflammation interactions and 5-HT synthesis between the gut and brain in chronic UC. METHODS: Dextran sulfate sodium (DSS) induced chronic UC mouse model was established to assess the therapeutic effect of corylin on chronic UC symptoms. The expression of inflammatory cytokines was detected in the colon and brain. The expression of tight junction (TJ) proteins of intestinal mucosal barrier and blood-brain barrier (BBB) and the ionized calcium-binding adaptor molecule 1 (Iba1) in the hippocampus were determined by western blotting and immunofluorescence staining. In addition, several tryptophan (Trp) metabolites and related neurotransmitters in faeces, colon, serum, and brain were detected by UPLC-MS/MS. The interaction between corylin and 5-hydroxytryptophan decarboxylase (5-HTPDC) was performed by molecular docking and surface plasmon resonance (SPR). Finally, the changes of gut microbiota composition were analyzed by 16S rRNA sequencing. RESULTS: Corylin significantly alleviated colitis symptoms and inhibited inflammatory response in the colon and brain of DSS-induced chronic UC mice. The TJ proteins of intestinal mucosal barrier and BBB were improved and the expression of Iba1 in the hippocampus was normalized after corylin treatment. In addition, corylin treatment increased the expression of neurotransmitters in the brain, especially 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP), but the expression of 5-HT in the colon was inhibited. Further study firstly proved that corylin could bind to the 5-HTDPC, and then inhibit the expression of 5-HTDPC and VB6, resulting in the 5-HT reduction and 5-HTP accumulation in the colon. Moreover, the intake of corylin transformed the diversity and composition of intestinal microbiota, Bacteroides, Escherichia-Shigella, and Turicibacter were decreased but Dubosiella, Enterorhabdus, and Candidatus_Stoquefichus were increased. CONCLUSION: Corylin administration ameliorated DSS-induced colitis and inhibited intestinal inflammation and neuroinflammation via regulating the inflammation interactions across gut-brain axis and increasing 5-HTP generation in the colon.

Biological analysis of constituents in Spatholobi Caulis by UFLC-MS/MS: Enhanced quantification and application to permeability properties study in Caco-2 cell monolayer model.

Major chemical constituents in medicinal materials are often used as the marker compounds of traditional Chinese medicine (TCM) for treating various diseases. For spatholobi caulis (SPC), it contains a variety of flavones, phenolic acid esters, and lignans which exert many pharmacological effects. However, the absorption and permeability properties of these constituents of SPC are still unclear and require further investigation. Different types and major compounds of SPC were chosen as representative constituents to study their absorption and transepithelial transport characteristics in the human intestinal epithelium-like Caco-2 cell monolayer model. 35 constituents of SPC were evaluated by using ultra fast liquid chromatography combined with electrospray ionization triple quadrupole tandem mass spectrometry (UFLC-MS/MS) method, acetonitrile and water containing with 0.5 mM ammonium acetate were used as mobile phase, these analytes with good linear relationships (R2 was within 0.9967-0.9998), precision (CV values were less than 10.23 %, LLOQ was less than 13.69 %), accuracy (Mean of inter- and intra-day were within 85.02 %-111.61 % and 85.50-112.97 %, respectively) and stability (The mean was within 85.07 %-113.93 %), among which 16 analytes showed good permeability, 5 analytes were considered to be poorly permeable compounds, and the other 14 analytes were assigned for the moderately absorbed compounds in Caco-2 cell monolayer model. The further results showed that the absorption mechanism of 7 well absorbed compounds, 8-O-methylretusin (1), genistein (7), spasuberol B (16), naringenin (18), isoliquiritigenin (19), 4-hydroxy-3-methoxy cinnamic acid methyl ester (23) and (+)-epipinoresinol (31) in SPC was mainly passive diffusion, their bidirectional transport rate was correlated with the concentration and transport time. The chemical structures of these compounds could affect the permeability properties on the cell monolayer. This study demonstrated the utility of Caco-2 cell monolayer model for evaluating the absorption properties and initial mechanisms of compounds in SPC in vitro, and provided important basis for predicting oral bioavailability of SPC compounds.

Flavonoids dimers from the fruits of Psoralea corylifolia and their cytotoxicity against MCF-7 cells.

Nine new flavonoids dimers, psocorylins R-Z (1-9), were isolated from the fruits of Psoralea corylifolia L. (Psoraleae Fructus), a traditional Chinese medicine. The structures of these compounds were elucidated via multiple spectroscopic techniques and X-ray diffraction. Psocorylins R (1) and S (2) were rare cyclobutane-containing chalcone dimers, and psocorylins T-Z (3-9) were established by CC or COC bond of two flavonoid monomers. The structural-types, flavonoids dimers, were isolated from the plant for the first time, enriching the chemical diversity. The cytotoxicity assay suggested that compounds 1, 2, 4, 5, 6 and 8 exhibited cytotoxic activities against MCF-7 cells. Furthermore, compounds 1 and 8 significantly increased intracellular ROS levels, decreased MMP and induced apoptosis of MCF-7 cells. They markedly upregulated the expression of Bax and cleaved caspase-3, and suppressed Bcl-2 and caspase-3 levels, indicating their mechanism of Bcl-2/Bax/Cleaved caspase-3 pathway. Hence, our findings not only promoted the chemical investigation of Psoraleae Fructus, but also provided potential bioactive natural products for anti-cancer.

Accurate Characterization of the Adhesive Layer Thickness of Ceramic Bonding Structures Using Terahertz Time-Domain Spectroscopy.

Ceramic adhesive structures have been increasingly used in aerospace applications. However, the peaks of the signal on the upper and lower surface of the adhesive layer are difficult to measure directly due to the thin thickness of the adhesive layer and the effect of the attenuation dispersion of the ceramic layer. Thus, the existing non-destructive testing techniques have been ineffective in detecting adhesive quality. In this paper, the thickness of the adhesive layer is measured using terahertz time-domain spectroscopy. A sparse deconvolution method is proposed for the terahertz time-domain spectral signal of ceramic adhesive structures with different adhesive layer thicknesses. The results show that the methods proposed in this paper can realize the separation of reflection signals for glue layers with a thickness of 0.20 mm. By comparing with a wavelet denoising method and a modified covariance method (AR/MCM), the effectiveness of the sparse deconvolution method in estimating the thickness of the glue layer is demonstrated. This work will provide the theoretical and experimental basis for using terahertz time-domain spectroscopy to detect the homogeneity of ceramic adhesive structures.

[Biotransformation of psoralenoside and isopsoralenoside in Psoraleae Fructus incubated with human intestinal bacteria flora in vitro].

Absorption is crucial to the resultant efficacy of oral drugs where the intestinal bacteria flora functions as one of the first-pass effects.The present study investigated the biotransformation of psoralenoside and isopsoralenoside in Chinese medicine Psoraleae Fructus(the dried fruit of Psoralea corylifolia) with the internationally recognized human intestinal bacteria flora model in vitro.Pso-ralenoside and isopsoralenoside were anaerobically incubated with human intestinal bacteria flora at 37 ℃, respectively, and biotransformation products were analyzed and identified using high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS) and comparison with reference standards.The main biotransformation products of psoralenoside were psoralen and a small amount of 6,7-furano-hydrocoumaric acid, and the main biotransformation products of isopsoralenoside were isopsoralen and a small amount of 5,6-furano-hydrocoumaric acid.

Crosstalk between CYP2E1 and PPARα substrates and agonists modulate adipose browning and obesity.

Although the functions of metabolic enzymes and nuclear receptors in controlling physiological homeostasis have been established, their crosstalk in modulating metabolic disease has not been explored. Genetic ablation of the xenobiotic-metabolizing cytochrome P450 enzyme CYP2E1 in mice markedly induced adipose browning and increased energy expenditure to improve obesity. CYP2E1 deficiency activated the expression of hepatic peroxisome proliferator-activated receptor alpha (PPARα) target genes, including fibroblast growth factor (FGF) 21, that upon release from the liver, enhanced adipose browning and energy expenditure to decrease obesity. Nineteen metabolites were increased in Cyp2e1-null mice as revealed by global untargeted metabolomics, among which four compounds, lysophosphatidylcholine and three polyunsaturated fatty acids were found to be directly metabolized by CYP2E1 and to serve as PPARα agonists, thus explaining how CYP2E1 deficiency causes hepatic PPARα activation through increasing cellular levels of endogenous PPARα agonists. Translationally, a CYP2E1 inhibitor was found to activate the PPARα-FGF21-beige adipose axis and decrease obesity in wild-type mice, but not in liver-specific Ppara-null mice. The present results establish a metabolic crosstalk between PPARα and CYP2E1 that supports the potential for a novel anti-obesity strategy of activating adipose tissue browning by targeting the CYP2E1 to modulate endogenous metabolites beyond its canonical role in xenobiotic-metabolism.

Super-resolution reconstruction of terahertz images based on a deep-learning network with a residual channel attention mechanism.

To date, the existing terahertz super-resolution reconstruction methods based on deep-learning networks have achieved noteworthy success. However, the terahertz image degradation process needs to fully consider the blur and noise of the high-frequency part of the image during the network training process, and cannot be replaced simply by interpolation, which has high complexity. The terahertz degradation model is systematically investigated, and effectively solves the above problems by introducing the remaining channel mechanism into the deep-learning network. On the one hand, an image degradation model suitable for the terahertz imaging process is adopted for the images in the training dataset, which improves the accuracy of network training. On the other hand, the residual channel attention mechanism is introduced to realize the adaptive adjustment of the dependence between network channels, which results in the network being more focused on the restoration of high-frequency information, thereby supporting the extraction of high-frequency edge details in the image. In addition, experimental results demonstrate that this method successfully improves the peak signal-to-noise ratios, and offers clearer edge details and a better overall reconstruction effect. We believe that this work may provide a new possibility to improve the resolution of terahertz images.

Characterization and quantification of ginsenosides from the root of Panax quinquefolius L. by integrating untargeted metabolites and targeted analysis using UPLC-Triple TOF-MS coupled with UFLC-ESI-MS/MS.

The root of Panax quinquefolius L. (RPQ) is considered as an important functional food and rich in bioactive components, ginsenosides. To comprehensively characterize ginsenosides and evaluate the quality of RPQ from different sources, UPLC-Triple TOF-MS coupled with UFLC-ESI-MS/MS was applied to untargeted metabolites and targeted analysis for the first time. In untargeted metabolites analysis, a total of 225 ginsenosides were identified from RPQ using UPLC-Triple TOF-MS combined with SWATH data-independent strategy. Furthermore, the contents of 39 targeted ginsenoside markers in 14 RPQ samples were analyzed by a rapid and sensitive UFLC-ESI-MS/MS method. In addition, the results of chemometric analysis showed the quality of American RPQ was distinguished from that of Chinese RPQ according to the amount of targeted ginsenosides. This newly developed approach provides a powerful tool for enriching the diversity of saponins database and assessing the quality of RPQ, which can be further extended to other ginseng products and functional foods.

Separation and Enrichment of Alkaloids from Coptidis Rhizoma and Euodiae Fructus by Macroporous Resin and Evaluation of the Effect on Bile Reflux Gastritis Rats.

The Zuojin Pill consists of Coptidis Rhizoma (CR) and Euodiae Fructus (EF). It has been a classic prescription for the treatment of gastrointestinal diseases in China since ancient times. Alkaloids are considered to be its main pharmacologically active substances. The authors of the present study investigated the feasibility of preparing high purity total alkaloids (TAs) from CR and EF extracts separately and evaluated the effect for the treatment of bile reflux gastritis (BRG). Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. were used in the study. An optimized method for the enrichment and purification of TAs with macroporous resin was established. Furthermore, qualitative analysis by using ultra-high performance liquid chromatography coupled with electrospray ionization and quadrupole-time of flight mass spectrometry (UHPLC-ESI-QTOF-MS) was explored to identify the components of purified TAs. Thirty-one compounds, thirty alkaloids and one phenolic compound, were identified or tentatively assigned by comparison with reference standards or literature data. A method of ultra-high performance liquid chromatography coupled with diode array detector (UHPLC-DAD) for quantitative analysis was also developed. The contents of nine alkaloids were determined. Moreover, a rat model of BRG was used to investigate the therapeutic effect of the combination of purified TAs from CR and EF. Gastric pathologic examination suggested that the alkaloids' combination could markedly attenuate the pathological changes of gastric mucosa.

Constituents promoting osteogenesis from the fruits of Psoralea corylifolia and their structure-activity relationship study.

The mature fruit of Psoralea corylifolia L. is a common traditional Chinese medicine used to tonify the kidney and yang, and as well as to treat osteoporosis. Systematic phytochemical investigations have established the most comprehensive constituent library to date, covering over 180 compounds. In this study, 109 chemical constituents containing 37 undescribed compounds were reported and incorrect structures of four known coumarins were corrected. The structures of these undescribed compounds were elucidated using spectroscopic methods, single-crystal X-ray diffraction, Rh2(OCOCF3)4 and Mo2(OAc)4-induced circular dichroism spectra. To identify potentially active compounds and investigate their structure-activity relationship (SAR), 89 constituents in the library were evaluated for their osteogenic differentiation and mineralisation activities in MC3T3-E1 cells. We found that coumarins, isoflavones, flavonones, and meroterpenoids were the material basis for Psoralea corylifolia-based treatment of osteoporosis, with some compounds exhibiting excellent activities. These compounds function via the estrogen receptor (ER) pathway and were natural phytoestrogen. Further SAR analysis showed that compounds with an intact isopentenyl replacement possessed superior activities, which was explained by their improved affinity with the ER.

Defect Detection of Composite Material Terahertz Image Based on Faster Region-Convolutional Neural Networks.

Terahertz (THz) nondestructive testing (NDT) technology has been increasingly applied to the internal defect detection of composite materials. However, the THz image is affected by background noise and power limitation, leading to poor THz image quality. The recognition rate based on traditional machine vision algorithms is not high. The above methods are usually unable to determine surface defects in a timely and accurate manner. In this paper, we propose a method to detect the internal defects of composite materials by using terahertz images based on a faster region-convolutional neural networks (faster R-CNNs) algorithm. Terahertz images showing internal defects in composite materials are first acquired by a terahertz time-domain spectroscopy system. Then the terahertz images are filtered, the blurred images are removed, and the remaining images are enhanced with data and annotated with image defects to create a dataset consistent with the internal defects of the material. On the basis of the above work, an improved faster R-CNN algorithm is proposed in this paper. The network can detect various defects in THz images by changing the backbone network, optimising the training parameters, and improving the prior box algorithm to improve the detection accuracy and efficiency of the network. By taking the commonly used composite sandwich structure as a representative, a sample with typical defects is designed, and the image data are obtained through the test. Comparing the proposed method with other existing network methods, the former proves to have the advantages of a short training time and high detection accuracy. The results show that the mean average precision (mAP) without data enhancement reached 95.50%, and the mAP with data enhancement reached 98.35% and exceeded the error rate of human eye detection (5%). Compared with the original faster R-CNN algorithm of 84.39% and 85.12%, the improvement is 11.11% and 10.23%, respectively, which demonstrates superb feature extraction capability and reduces the occurrence of network errors and omissions.

Chemical Fingerprint Analysis and Quantitative Analysis of Saccharides in Morindae Officinalis Radix by HPLC-ELSD.

A method based on high performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD) was developed for the quantitative analysis of three active compounds and chemical fingerprint analyses of saccharides in Morindae officinalis radix. Ten batches of Morindae officinalis radix were collected from different plantations in the Guangdong region of China and used to establish the fingerprint. The samples were separated with a COSMOIL Sugar-D column (4.6 mm × 250 mm, 5 µm) by using gradient elution with water (A) and acetonitrile (B). In addition, Trapped-Ion-Mobility (tims) Time-Of-Flight (tims TOF) was used to identify saccharides of Morindae officinalis radix. Fingerprint chromatogram presented 26 common characteristic peaks in the roots of Morinda officinalis How, and the similarities were more than 0.926. In quantitative analysis, the three compounds showed good regression (r = 0.9995-0.9998) within the test ranges, and the recoveries of the method were in the range of 96.7-101.7%. The contents of sucrose, kestose and nystose in all samples were determined as 1.21-7.92%, 1.02-3.37%, and 2.38-6.55%, respectively. The developed HPLC fingerprint method is reliable and was validated for the quality control and identification of Morindae officinalis radix and can be successfully used to assess the quality of Morindae officinalis radix.

Polyamine metabolism links gut microbiota and testicular dysfunction.

BACKGROUND: Male fertility impaired by exogenous toxins is a serious worldwide issue threatening the health of the new-born and causing infertility. However, the metabolic connection between toxic exposures and testicular dysfunction remains unclear. RESULTS: In the present study, the metabolic disorder of testicular dysfunction was investigated using triptolide-induced testicular injury in mice. We found that triptolide induced spermine deficiency resulting from disruption of polyamine biosynthesis and uptake in testis, and perturbation of the gut microbiota. Supplementation with exogenous spermine reversed triptolide-induced testicular dysfunction through increasing the expression of genes related to early and late spermatogenic events, as well as increasing the reduced number of offspring. Loss of gut microbiota by antibiotic treatment resulted in depletion of spermine levels in the intestine and potentiation of testicular injury. Testicular dysfunction in triptolide-treated mice was reversed by gut microbial transplantation from untreated mice and supplementation with polyamine-producing Parabacteroides distasonis. The protective effect of spermine during testicular injury was largely dependent on upregulation of heat shock protein 70s (HSP70s) both in vivo and in vitro. CONCLUSIONS: The present study linked alterations in the gut microbiota to testicular dysfunction through disruption of polyamine metabolism. The diversity and dynamics of the gut microbiota may be considered as a therapeutic option to prevent male infertility. Video Abstract.