Ursolic acid (UA), a natural triterpenoid widely distributed within fruits and edible plants, has been proven to relieve alcoholic liver disease (ALD). However, the mechanisms involved largely remain ...unclear. This study investigated whether the beneficial effects of UA on ALD could be related to gut–liver axis (GLA) modulation. Special attention was paid to the contribution of gut microbiome manipulation. UA ameliorated intestinal oxidative stress and barrier dysfunction induced by alcohol. As a consequence of gut leakiness amelioration, the related endotoxemia-mediated liver toll-like receptor 4 pathway induction and the subsequent reactive oxygen species overproduction were reverted. UA also counteracted alcohol-induced gut dysbiosis. A fecal microbiota transplantation study indicated that liver injury as well as ileum oxidative stress and gut barrier dysfunction of recipient mice were partly ameliorated as a result of microbiome remodeling. These results suggest that dietary UA alleviates ALD through GLA homeostasis modulation. Gut microbiome manipulation contributes to the hepatoprotective activity and GLA modulating effect of UA.
Connecting different electronic devices is usually straightforward because they have paired, standardized interfaces, in which the shapes and sizes match each other perfectly. Tissue-electronics ...interfaces, however, cannot be standardized, because tissues are soft
and have arbitrary shapes and sizes
. Shape-adaptive wrapping and covering around irregularly sized and shaped objects have been achieved using heat-shrink films because they can contract largely and rapidly when heated
. However, these materials are unsuitable for biological applications because they are usually much harder than tissues and contract at temperatures higher than 90 °C (refs.
). Therefore, it is challenging to prepare stimuli-responsive films with large and rapid contractions for which the stimuli and mechanical properties are compatible with vulnerable tissues and electronic integration processes. Here, inspired by spider silk
, we designed water-responsive supercontractile polymer films composed of poly(ethylene oxide) and poly(ethylene glycol)-α-cyclodextrin inclusion complex, which are initially dry, flexible and stable under ambient conditions, contract by more than 50% of their original length within seconds (about 30% per second) after wetting and become soft (about 100 kPa) and stretchable (around 600%) hydrogel thin films thereafter. This supercontraction is attributed to the aligned microporous hierarchical structures of the films, which also facilitate electronic integration. We used this film to fabricate shape-adaptive electrode arrays that simplify the implantation procedure through supercontraction and conformally wrap around nerves, muscles and hearts of different sizes when wetted for in vivo nerve stimulation and electrophysiological signal recording. This study demonstrates that this water-responsive material can play an important part in shaping the next-generation tissue-electronics interfaces as well as broadening the biomedical application of shape-adaptive materials.
Sparganii Rhizoma (SR), a traditional Chinese medicine (TCM), is the rhizome of Sparganium stoloniferum Buch.-Ham. mainly distributed in East Asia. It has been used for eliminating blood stasis, ...promoting the flow of Qi, removing the retention of undigested food and relieving pain in China for hundreds of years.
This review summarizes comprehensive information in traditional clinical application, processing, phytochemistry, pharmacology, quality control and toxicity of SR, in exploring future scientific and therapeutic potentials.
Pertinent information was systematically collected from several electronic scientific databases (e.g., Web of Science, PubMed, China Knowledge Resource Integrated, Springer, Elsevier, ScienceDirect, and Google Scholar), PhD and MS dissertations, and classic Chinese medical books.
SR is a gynecological drug which is often used to treat dysmenorrhea, mass in the abdomen, amenorrhea due to blood stasis, and abdominal distension in TCM. Two kinds of processed products of SR are included in Chinese Pharmacopoeia, which have better pharmacological effects than the crude herb. Approximately 180 compounds have been identified from SR, including phenylpropanoids, flavonoids, anthraquinones, organic acids, alkaloids, steroids, volatile oils, diarylheptanes, etc. The crude extracts and isolated components of SR have been reported to have anti-tumor, antithrombotic, estrogen antagonistic , anti-inflammatory, analgesic, antioxidant, anti organ fibrosis and other pharmacological activities. SR also has reproductive toxicity.
As an important TCM, SR has been demonstrated by modern pharmacological researches to have significant bioactivities, especially on anti-tumor, antithrombotic, and estrogen antagonistic activities. These activities provide prospects for the development of new drugs and therapeutics for future applications. Nevertheless, quality control and evaluation, in-depth pharmacological mechanism, and toxicological effect of SR require further detailed research.
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•Relatively comprehensive information of chemical components in Ezhu was obtained.•Chemometrics coupled with chromatography discriminated Ezhu with the three species.•Potential ...chemical markers for the species authentication of Ezhu were discovered.•The marker-based discriminatory strategy is rapid for the species authentication.
Curcumae Rhizoma (Ezhu), a multi-origin Chinese medicine, originates from the dry rhizomes of C. kwangsiensis, C. phaeocaulis and C. wenyujin. The three species have great variation in chemical components and therapeutic effects. To improve safety and effectiveness in clinical use, a strategy integrating chromatographic analysis and chemometrics for the species authentication of Ezhu was proposed. Firstly, systematic analysis of chemical compositions in Ezhu was achieved using high performance liquid chromatography (HPLC) fingerprint and headspace gas chromatography-mass spectrometry (HS-GC–MS). HPLC fingerprints showed that seventeen peaks in common for C. kwangsiensis and eleven peaks in common for C. wenyujin both presented a good similarity (> 0.9, only several samples < 0.8). Eleven common peaks in C. phaeocaulis and the similarity values of most samples were higher than 0.700. Additionally, there were ten common peaks in all Ezhu samples and they had relatively poor similarity with the correlation coefficients ranging from 0.364 to 0.881. For HS-GC–MS, thirty-six volatile components were identified in the three species of Ezhu, mainly monoterpenes and sesquiterpenes. Subsequently, chemometrics including unsupervised principal component analysis (PCA), supervised linear discriminant analysis (LDA), K-nearest neighbors (KNN), back propagation neural network (BP-NN) and orthogonal partial least squares-discrimination analysis (OPLS-DA) was applied to extract useful information from chromatographic profiles. Based on HPLC fingerprint data, PCA could hardly differentiate Ezhu with the three species, and LDA, KNN and BP-NN models provided more than 85 % correct identification. With HS-GC–MS data, PCA could only distinguish C. wenyujin from the other two species, and LDA, KNN, BP-NN and OPLS-DA models achieved excellent classification with 100 % accuracy. Finally, five volatile components (eucalyptol, humulene, β-elemene, (+)-2-bornanone and linalool) with variable importance for the projection (VIP) values higher than 1 in the OPLS-DA model were selected as potential chemical markers for the species authentication of Ezhu. And the constructed OPLS-DA model using these markers obtained 100 % accuracy. Consequently, a rapid, precise and feasible strategy was established for the discrimination and quality control of Ezhu with different species.
Thymus quinquecostatus Celak. has been widely used as a spice and a folk medicine for relieving exterior syndrome and alleviating pain in China.
To explore the protective effects and the underlying ...mechanism against cerebral ischemia-reperfusion injury (CIRI) of the T. quinquecostatus combining with its chemical composition.
High-polar extract (HPE) was extracted from T. quinquecostatus and polyphenols in HPE were enriched to obtain polyphenol-rich fraction (PRF) using Macroporous resin. The free radicals and zebrafish embryos were used to compare the antioxidant activities of HPE and PRF in vitro and in vivo. Then, the transient middle cerebral artery occlusion (tMCAO) model was established in rats. Neurological deficit score, infarction rate, morphology and apoptosis of neurons were examined to investigate the protective effects of PRF on CIRI. The mRNA and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1) and the activities of downstream antioxidant enzymes in ischemia tissues were determined to clarify the underlying mechanisms. Also, reactive oxygen species (ROS) level in zebrafish embryos were detected after incubation with PRF for a short time (2 h) to investigate whether PRF could directly eliminate free radicals. Finally, chemical composition of PRF were analyzed to investigate the material basis for antioxidant activity and anti-CIRI effect.
Compared with HPE, PRF showed stronger antioxidant activities. PRF exhibited obvious protective effects including ameliorating neurological deficit, lowering infarction rate, and improving the cellular morphology in hippocampus CA1 and cortex after tMCAO. TUNEL staining suggested PRF dose-dependently improved the apoptosis of the neurons in ischemic cortex. RT-qPCR and Western Blot results suggested that PRF regulated oxidative stress (OS) via activating the Keap1/Nrf2/HO-1 signaling pathway. Also, PRF could directly scavenge excessive ROS in zebrafish embryos after a short-time PRF incubation. The anti-CIRI effect might be primarily attributed to the abundant polyphenols in PRF, including flavonoids, polymethoxylated flavonoids, flavonoid glycosides, and phenolic acids.
T. quinquecostatus contains abundant polyphenols and exhibited a good protective effect against CIRI via dual antioxidant mechanisms, providing a reference for further research and application for this plant.
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Baoyuan Decoction (BYD) was initially recorded in the classic of “Bo Ai Xin Jian” in the Ming dynasty. It is traditionally used for treating weakness and cowardice, and deficiency of vital energy. In ...researches related to anti-fatigue effects, the reciprocal regulation of AMPK and circadian clocks likely plays an important role in anti-fatigue mechanism, while it has not yet been revealed. Therefore, we elucidated the anti-fatigue mechanism of BYD through AMPK/CRY2/PER1 pathway.
To investigate the effect and mechanism of BYD in reducing fatigue, using pharmacodynamics, network pharmacology and transcriptomics through the AMPK/CRY2/PER1 signaling pathway.
Firstly, the chemical constituents of BYD were qualitatively identified by UHPLC-Q-Exactive Orbitrap/MS, establishing a comprehensive strategy with an in-house library, Xcalibur software and Pubchem combined. Secondly, a Na2SO3-induced fatigue model and 2,2′-Azobis (2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative stress model were developed to evaluate the anti-fatigue and anti-oxidant activities of BYD using AB zebrafish. The anti-inflammatory activity of BYD was evaluated using CuSO4-induced and tail cutting-induced Tg (lyz: dsRed) transgenic zebrafish inflammation models. Then, target screening was performed by Swiss ADME, GeneCards, OMIM and DrugBank databases, the network was constructed using Cytoscape 3.9.0. Transcriptome and network pharmacology technology were used to investigate the related signaling pathways and potential mechanisms after treatment with BYD, which were verified by real-time quantitative PCR (RT-qPCR).
In total, 114 compounds from the water extract of BYD were identified as major compounds. Na₂SO₃-induced fatigue model and AAPH-induced oxidative stress model indicated that BYD has significant anti-fatigue and antioxidant effects. Meanwhile, BYD showed significant anti-inflammatory effects on CuSO4-induced and tail cutting-induced zebrafish inflammation models. The KEGG result of network pharmacology showed that the anti-fatigue function of BYD was mainly effected through AMPK signaling pathway. Besides, transcriptome analysis indicated that the circadian rhythm, AMPK and IL-17 signaling pathways were recommended as the main pathways related to the anti-fatigue effect of BYD. The RT-qPCR results showed that compared with a model control group, the treatment of BYD significantly elevated the expression mRNA of AMPK, CRY2 and PER1.
Herein, we identified 114 chemical constituents of BYD, performed zebrafish activity validation, while demonstrated that BYD can relieve fatigue by AMPK/CRY2/PER1 signaling pathway through network pharmacology and transcriptome.
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•One hundred and fourteen chemical components of BYD were identified by UHPLC-Q-Exactive Orbitrap/MS technology.•BYD significantly inhibited Na2SO3-induced fatigue and AAPH-induced oxidation in zebrafish.•BYD showed significant anti-inflammatory effects on CuSO4-induced and tail cutting-induced zebrafish inflammation models.•We obtained AMPK/CRY2/PER1 signaling pathway through integrated analysis of network pharmacology and transcriptomic.
Curcumae Radix (Yujin) has a long medicinal use history in China, which is used to cure diseases like jaundice, cholelithiasis caused by dampness-heat of gallbladder and liver, and so on. It comes ...from the dried tuberous roots of C. kwangsiensis (Guiyujin), C. longa (Huangyujin), C. phaeocaulis (Lvyujin) and C. wenyujin (Wenyujin). Though there are differences in chemical compositions and pharmacological activities among the four species of Yujin, they have not been differentiated well in clinical application due to their similar morphological characterizations.
In this study, the four species of Yujin were rapidly and accurately discriminated. The potential volatile markers for varietal recognition were identified.
Attenuated total reflection fourier transformed infrared (ATR-FTIR) spectroscopy combined with chemometrics was used to rapidly discriminate the four species of Yujin. Headspace-gas chromatography-mass spectrometry (HS-GC-MS) technology coupled with chemometrics was employed to characterize volatile profiling, differentiate species and select potential markers for varietal recognition of Yujin.
By applying PCA (principal components analysis) and HCA (hierarchical cluster analysis), HS-GC-MS realized complete differentiation of the four species of Yujin, while ATR-FTIR only recognized Guiyuijin. Back propagation neural network (BP-NN), KNN (K-nearest neighbor) and LDA (linear discriminant analysis) models based on spectral data achieved 100% discriminant accuracies. Support vector machines (SVM), KNN and PLS-DA (partial least square discriminant analysis) models based on volatile compounds also realized 100% discriminant accuracies. Additionally, the potential volatile markers for varietal recognition of Yujin were screened using PLS-DA, including 2 for Guiyujin, 6 for Lvyujin, 9 for Wenyujin and 13 for Huangyujin.
The present study developed reliable methods for the varietal discrimination and volatile compounds characterization of Yujin, which will provide references for its quality control and clinical efficacy.
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•Spectra properties for the four species of Yujin were characterized by ATR-FTIR.•Volatile compounds of Yujin with four origins were identified by HS-GC-MS.•PCA and HCA based on HS-GC-MS successfully separated the four sources of Yujin.•Discrimination models with ATR-FTIR and HS-GC-MS severally obtained 100% accuracies.•The potential volatile markers for varietal recognition of Yujin were screened out.
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•The four species of Yujin were discriminated by NIR combined with chemometrics.•Six compounds including sesquiterpenoids and curcuminoids were determined by HPLC.•The SVMR model ...based on NIR was established to quickly predict germacrone content.
Curcumae Radix (Yujin) is a multi-origin herbal medicine with excellent clinical efficacy. For fast discrimination and quantification analysis of Yujin from four botanical origins (Guiyujin, Huangyujin, Lvyujin and Wenyujin), near infrared (NIR) spectroscopy combined with chemometrics tools was employed in this study. Based on NIR data, principal component analysis (PCA) could only realize the separation between Guiyujin and Wenyujin samples, and the partial least squares-discrimination analysis (PLS-DA), support vector machine (SVM) and k-nearest neighbors (KNN) models achieved the complete discrimination of the four species of Yujin with 100% accuracy. Moreover, the method for the simultaneous determination of six bioactive compounds in Yujin was developed by HPLC. Germacrone, curdione and curcumenol could be found in all samples, and curcumin, demethoxycurcumin and bisdemethoxycurcumin were only observed in Huangyujin samples. Then, the support vector machine regression (SVMR) model for the prediction of germacrone content was successfully constructed. And the coefficients of determination were 0.88 and 0.89 for calibration and validation sets, respectively. The present work proposes a quick, economic and reliable method for the discrimination of Yujin from four botanical origins and the prediction of germacrone content, which will contribute to its quality control researches.
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•Eleven components in Curcumae Rhizoma were determined simultaneously by HPLC.•The three species of Curcumae Rhizoma were rapidly discriminated by UV and HPLC with chemometrics (DT, ...LDA, SVM and KNN).•PLS and BP-ANN models were constructed to predict the contents of three chemical chemical component in Curcumae Rhizoma.
Curcumae Rhizoma (Ezhu in Chinese) is a multi-origin herbal medicine with excellent clinical efficacy. For fast discrimination and quantification analysis of Ezhu from three botanical origins (Curcuma kwangsiensis, Curcuma phaeocaulis, and Curcuma wenyujin), ultra-violet (UV) spectroscopy and high performance liquid chromatography (HPLC) combined with chemometric tools were employed in this study. Firstly, the analysis method for the simultaneous determination of eleven compounds in Ezhu was developed by HPLC, and the UV spectra of thirty-eight batches of Ezhu were acquired. Then, principal component analysis (PCA), an unsupervised pattern recognition method, was applied on the HPLC and UV spectral data. PCA did not show a clear separation between C. phaeocaulis and C. wenyujin samples with HPLC data. By contrast, the supervised techniques, decision tree (DT) and linear discriminant analysis (LDA), achieved the complete discrimination for the three species of Ezhu with 100 % correct classification rate (CCR), showing excellent performance. Based on UV spectral data, PCA presented good performance for discriminating the three species of Ezhu. LDA, support vector machine (SVM) and k-nearest neighbors (KNN) models provided 96.3 % CCR for the calibration set and 100 % CCR for the validation set. Moreover, the partial least squares (PLS) and back propagation-artificial neural network (BP-ANN) quantitative models established on UV spectral data were satisfactory in predicting the contents of zederone, curdione and 3,5-dihydroxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptane. The residual predictive deviation (RPD) for zederone, curdione and 3,5-dihydroxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptane of PLS models were 3.169, 1.502 and 1.735, and that of BP-ANN models were 3.467, 2.481 and 2.370, respectively. The present work proposed a rapid and reliable method for the discrimination of Ezhu from three botanical origins and the prediction of zederone, curdione and 3,5-dihydroxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-heptane contents in Ezhu, which will help a lot in the quality control of Ezhu and other multi-origin herbal medicines.
•HPLC fingerprints of single species and full samples were separately developed.•UV–Vis spectra showed there were three peaks in Huangyujin and one in others.•Discrimination models were respectively ...established based on the two techniques.•Quantification models based on UV–Vis spectra were used to determine three compounds.
Curcumae Radix with four botanical origins (Wenyujin, Huangyujin, Guiyujin, Lvyujin) has a long medical history in China. The four species have not been differentiated well in clinical application, though there were differences in pharmacological effects among them. For the aim of fast discrimination and quantitative analysis of Yujin, HPLC (high performance liquid chromatography) fingerprint and UV–Vis (ultraviolet–visible) spectroscopy technologies coupled with chemometrics were employed. The HPLC fingerprints of 26 Guiyujin, 11 Huangyujin, 11 Lvyujin, 29 Wenyujin and full 77 samples were separately established, with good similarities among same species except Wenyujin and poor consistence in full samples. UV–Vis spectra showed obvious three absorption peaks in the spectra of Huangyujin samples and only one in that of the rest samples. LDA (linear discriminant analysis) and Bagged Trees models established based on HPLC fingerprint data attained higher than 90% discrimination accuracy. Based on the spectral data, complete separation for the four species of Yujin was failed to achieve by PCA (principal component analysis), and the KNN (k-nearest neighbors) and SVM (support vector machine) models achieved no<90% discrimination accuracies. Furthermore, the SVMR (support vector machine regression) and Bagged Trees Regression models used to quickly predict the contents of germacrone, curcumenol and curdione performed well, with relatively lower RMSE (root mean square error) and higher R2 (coefficient of determination) values. The present study proposed relatively rapid methods for the determination of bioactive compounds and discrimination of Yujin.
