Exposure to heavy metallic and trace essential elements and risk of diminished ovarian reserve in reproductive age women: A case-control study.

The associations between metallic elements and ovarian reserve function have remained uncertain yet. In this case-control study, we involved 149 women with diminished ovarian reserve (DOR) and 151 women with normal ovarian reserve, and assessed the levels of six heavy metallic (Cr, Cd, As, Hg, Pb, and Mn) and seven trace essential (Se, Fe, Zn, Co, Mo, Cu, I) elements in their follicular fluid with inductively coupled plasma mass spectrometry. Associations were examined with logistic regressions and Bayesian kernel machine regression (BKMR). As a result, we found that the medium and the highest tertiles of Pb were significantly associated with an increased likelihood of DOR compared to the lowest tertile, while the medium or/an the highest tertiles of Cu, I, and Fe showed significantly lower likelihoods of DOR compared to the lowest tertiles. Cu and Pb showed significantly non-linear associations with ovarian reserve markers such as follicle-stimulating, anti-mullerian hormone levels, and antral follicle count. With the rising overall concentrations of heavy metals, the likelihood of DOR increased although not significant. There was a trend of a "U-shaped" association across the whole concentration range of trace essential elements and the likelihood of DOR. Our study revealed that avoiding heavy metallic elements and properly supplementing trace essential elements are conducive to ovarian function.

Nuciferine reduces inflammation induced by cerebral ischemia-reperfusion injury through the PI3K/Akt/NF-κB pathway.

BACKGROUND: Cerebral ischemia has the characteristics of high incidence, mortality, and disability, which seriously damages people's health. Cerebral ischemia-reperfusion injury is the key pathological injury of this disease. However, there is a lack of drugs that can reduce cerebral ischemia-reperfusion injury in clinical practice. At present, a few studies have provided some evidence that nuciferine can reduce cerebral ischemia-reperfusion injury, but its specific mechanism of action is still unclear, and further research is still needed. OBJECTIVE: In this study, PC12 cells and SD rats were used to construct OGD/R and MCAO/R models, respectively. Combined with bioinformatics methods and experimental verification methods, the purpose of this study was to conduct a systematic and comprehensive study on the effect and mechanism of nuciferine on reducing inflammation induced by cerebral ischemia-reperfusion injury. RESULTS: Nuciferine can improve the cell viability of PC12 cells induced by OGD/R, reduce apoptosis, and reduce the expression of inflammation-related proteins; it can also improve the cognitive and motor dysfunction of MCAO/R-induced rats by behavioral tests, reduce the area of cerebral infarction, reduce the release of inflammatory factors TNF-α and IL-6 in serum and the expression of inflammation-related proteins in brain tissue. CONCLUSION: Nuciferine can reduce the inflammatory level of cerebral ischemia-reperfusion injury in vivo and in vitro models by acting on the PI3K/Akt/NF-κB signaling pathway, and has the potential to be developed as a drug for the treatment of cerebral ischemia-reperfusion injury.

Characteristic volatiles of Fu brick tea formed primarily by extracellular enzymes during Aspergillus cristatus fermentation.

Fu brick tea (FBT) has unique "fungal flower" aroma traits, but its source of crucial aroma compounds is still controversial. Aspergillus cristatus is the dominant fungus that participated in the fermentation of FBT. In this study, volatiles of Aspergillus cristatus and corresponding fermented FBT were examined using GC × GC-Q-TOFMS. A total of 59 volatiles were shared by three strains of Aspergillus cristatus isolated from representative FBT. Among them, 1-octen-3-ol and 3-octanone were the most abundant. A total of 133 volatiles were screened as typical FBT volatiles from three FBTs fermented by the corresponding fungi. Aspergillus cristatus and FBT had only 29 coexisting volatiles, indicating that the volatiles of Aspergillus cristatus could not directly contribute to the aroma of FBT. The results of no significant correlation between volatile content in FBT and volatile content in Aspergillus cristatus suggested that intracellular metabolism of Aspergillus cristatus was not a direct driver of FBT aroma formation. Metabolic pathway analysis and proteomic analysis showed that the aroma in FBT was mainly formed by the enzymatic reaction of extracellular enzymes from Aspergillus cristatus. This study enriched our understanding of Aspergillus cristatus in the aroma formation process of FBT.

Toxicity study of compound granules of Hedyotis diffusa: Acute toxicity and long-term toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: The clinical efficacy of the hospital preparation compound granules of Hedyotis diffusa (CGHD), which is composed of Hedyotis diffusa Willd, Smilax china L., Solanum lyratum Thunb., has accumulated a good reputation over the past decades. However, because it is a hospital preparation, few researchers have paid attention to it, resulting in a lack of systematic basic research studies. Thus, it is not clear whether there are safety concerns that restrict its clinical application, and toxicological evaluation of CGHD is needed. AIM OF THE STUDY: The aim of this study was to evaluate the safety of CGHD by conducting acute toxicity and long-term toxicity experiments, with the objective of providing evidence for its clinical safety and a theoretical foundation for its clinical application. MATERIALS AND METHODS: KM mice were selected for the acute toxicity experiment and were administered water or CGHD-E 3 times within 24 h. The reactions of the animals to CGHD treatment were observed and recorded within 1 h after administration and then once a day for 14 consecutive days. SD rats were selected to conduct the long-term toxicity experiment. The drug-treated groups were administered different doses of CGHD-E, which were equivalent to 10 times, 20 times and 50 times the clinical dose in humans. The rats were administered the drug for 28 consecutive days. After 28 days, the animals were sacrificed, and routine blood tests, blood coagulation function analysis, liver and kidney function tests, and glycolipid metabolism related tests were conducted. The major organs of the rats were collected to calculate organ coefficients and perform hematoxylin-eosin (HE) staining. RESULTS: In the CGHD-E acute toxicity experiment, the drug-treated groups did not show adverse reactions or poisoning symptoms, and the maximum tolerated dose of CGHD-E in mice was greater than 45.072 g/kg. In the long-term toxicity experiment, drug-treated rats generally exhibited a good condition, but continuous administration decreased on body weight and food intake, especially in male rats. Coagulation function alterations and the impact on the liver during long-term drug administration were also assessed, which should be emphasized in clinical applications. No significant toxic effects were observed according to routine blood tests or test of liver and kidney function, glucose and lipid metabolism, or ion metabolism. CONCLUSIONS: The results of this study showed that CGHD was nontoxic or had low toxicity, providing not only a scientific basis for its clinical application, determining the appropriate clinical dose and monitoring clinical toxicity but also theoretical support for subsequent clinical drug trials.

Quality markers of Dajianzhong decoction based on multicomponent qualitative and quantitative analysis combined with network pharmacology and chemometric analysis.

INTRODUCTION: Dajianzhong decoction (DJZD), a classic famous prescription, has a long history of medicinal application. Modern studies have demonstrated its clinical utility in the treatment of postoperative ileus (POI). But none of the current quality evaluation methods for this compound is associated with efficacy. OBJECTIVES: This study aimed to identify the quality markers (Q-Markers) connected to the treatment of POI in DJZD. METHODOLOGY: Ultra-performance liquid chromatography quadrupole Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap-MS) was used to identify the main constituents in DJZD. Based on the qualitative results obtained by fingerprinting, chemical pattern recognition (CPR) was used to analyse the key components affecting the quality and finally to establish the network of the active ingredients in DJZD with POI. RESULTS: A total of 64 chemical components were detected. After fingerprint analysis, 13 common peaks were identified. The fingerprint similarity of 15 batches of samples ranged from 0.860 to 1.000. CPR analysis was able to categorically classify 15 batches of DJZD into two groups. And gingerenone A, methyl-6-gingerdiol, 6-gingerol, and hydroxy-ß-sanshool contributed to their grouping. Twelve common components interact with the therapeutic targets for treating POI. In addition, the mechanism of this prescription for treating POI may be related to the jurisdiction of the neurological system, the immunological system, and the inflammatory response. CONCLUSIONS: This integrated approach can accurately assess and forecast the quality of DJZD, presume the Q-Markers of DJZD for POI, and lay the foundation for studying the theoretical underpinnings and exploring the mechanism of DJZD in the treatment of POI.

Effect and molecular mechanism of Sulforaphane alleviates brain damage caused by acute carbon monoxide poisoning:Network pharmacology analysis, molecular docking, and experimental evidence.

Sulforaphane (SFN) has attracted much attention due to its ability on antioxidant, anti-inflammatory, and anti-apoptotic properties, while its functional targets and underlying mechanism of action on brain injury caused by acute carbon monoxide poisoning (ACOP) have not been fully elucidated. Herein, we used a systematic network pharmacology approach to explore the mechanism of SFN in the treatment of brain damage after ACOP. In this study, the results of network pharmacology demonstrated that there were a total of 81 effective target genes of SFN and 36 drug-disease targets, which were strongly in connection with autophagy-animal signaling pathway, drug metabolism, and transcription disorders in cancer. Upon the further biological function and KEGG signaling pathway enrichment analysis, a large number of them were involved in neuronal death, reactive oxygen metabolic processes and immune functions. Moreover, based on the results of bioinformatics prediction associated with multiple potential targets and pathways, the AMP-activated protein kinase (AMPK) signaling pathway was selected to elucidate the molecular mechanism of SFN in the treatment of brain injury caused by ACOP. The following molecular docking analysis also confirmed that SFN can bind to AMPKα well through chemical bonds. In addition, an animal model of ACOP was established by exposure to carbon monoxide in a hyperbaric oxygen chamber to verify the predicted results of network pharmacology. We found that the mitochondrial ultrastructure of neurons in rats with ACOP was seriously damaged, and apoptotic cells increased significantly. The histopathological changes were obviously alleviated, apoptosis of cortical neurons was inhibited, and the number of Nissl bodies was increased in the SFN group as compared with the ACOP group (p < .05). Besides, the administration of SFN could increase the expressions of phosphorylated P-AMPK and MFN2 proteins and decrease the levels of DRP1, Caspase3, and Casapase9 proteins in the brain tissue of ACOP rats. These findings suggest that network pharmacology is a useful tool for traditional Chinese medicine (TCM) research, SFN can effectively inhibit apoptosis, protect cortical neurons from the toxicity of carbon monoxide through activating the AMPK pathway and may become a potential therapeutic strategy for brain injury after ACOP.

Three new Furano-lactones from the endophytic fungus Aspergillus nidulans.

Three new furano-lactones, asperilactones A-C (1-3), and two known compounds silvaticol (4) and violaceic acid (5) were isolated from an ethanol extract of Aspergillus nidulans, a fungus isolated from the Annelida Whitmania pigra Whitman (Haemopidae). Their structures were elucidated by a combination of spectroscopy, ECD calculations, comparing optical rotation values, and single-crystal X-ray diffraction analyses. Asperilactone A (1) represented the first example of furano-lactone with an unusual 2-thia-6-oxabicyclo[3.3.0]octane ring system. Asperilactones A and B showed weak toxicity against the HL-60 and RKO.

[Protective effect of Liujing Toutong Tablets on rats with permanent cerebral ischemia via NF-κB signaling pathway].

This study investigated the neuroprotective effects and underlying mechanism of Liujing Toutong Tablets(LJTT) on a rat model of permanent middle cerebral artery occlusion(pMCAO). The pMCAO model was established using the suture method. Eighty-four male SPF-grade SD rats were randomly divided into a sham operation group, a model group, a nimodipine group(0.020 g·kg~(-1)), and high-, medium-, and low-dose LJTT groups(2.8, 1.4, and 0.7 g·kg~(-1)). The Longa score, adhesive removal test and laser speckle contrast imaging technique were used to evaluate the degree of neurological functional impairment and changes in local cerebral blood flow. The survival and mortality of rats in each group were recorded daily. After seven days of continuous administration following the model induction, the rats in each group were euthanized, and brain tissue and blood samples were collected for corresponding parameter measurements. Nissl staining was used to examine pathological changes in brain tissue neurons. The levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-1ß, vascular endothelial growth factor(VEGF), calcitonin gene-related peptide(CGRP), beta-endorphin(ß-EP), and endogenous nitric oxide(NO) in rat serum were measured using specific assay kits. The entropy weight method was used to analyze the weights of various indicators. The protein expression levels of nuclear factor kappa-B(NF-κB), inhibitor kappaB alpha(IκBα), phosphorylated IκBα(p-IκBα), and phosphorylated inhibitor of NF-κB kinase alpha(p-IKKα) in brain tissue were determined using Western blot. Immunohistochemistry was used to detect the protein expression of chemokine-like factor 1(CKLF1) and C-C chemokine receptor 5(CCR5) in rat brain tissue. Compared with the sham operation group, the model group showed significantly higher neurological functional impairment scores, prolonged adhesive removal time, decreased cerebral blood flow, increased neuronal damage, reduced survival rate, significantly increased levels of TNF-α, IL-1ß, IL-6, CGRP, and NO in serum, significantly decreased levels of VEGF and ß-EP, significantly increased expression levels of NF-κB p65, p-IκBα/IκBα, and p-IKKα in rat brain tissue, and significantly upregulated protein expression of CKLF1 and CCR5. Compared with the model group, the high-dose LJTT group significantly improved the neurological functional score of pMCAO rats after oral administration for 7 days. LJTT at all doses significantly reduced adhesive removal time and restored cerebral blood flow. The high-and medium-dose LJTT groups significantly improved neuronal damage. The LJTT groups at all doses showed reduced levels of TNF-α, IL-1ß, IL-6, CGRP, and NO in rat serum, increased VEGF and ß-EP levels, and significantly decreased expression levels of NF-κB p65, p-IκBα/IκBα, p-IKKα, and CCR5 protein in rat brain tissue. The entropy weight analysis revealed that CGRP and ß-EP were significantly affected during the model induction, and LJTT exhibited a strong effect in reducing the release of inflammatory factors such as TNF-α and IL-1ß. LJTT may exert a neuroprotective effect on rats with permanent cerebral ischemia by reducing neuroinflammatory damage, and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the regulation of the CKLF1/CCR5 axis. Additionally, LJTT may exert certain analgesic effects by reducing CGRP and NO levels and increasing ß-EP levels.

A Review on Rhizosphere Microbiota of Tea Plant (Camellia sinensis L): Recent Insights and Future Perspectives.

Rhizosphere microbial colonization of the tea plant provides many beneficial functions for the host, But the factors that influence the composition of these rhizosphere microbes and their functions are still unknown. In order to explore the interaction between tea plants and rhizosphere microorganisms, we summarized the current studies. First, the review integrated the known rhizosphere microbial communities of tea tree, including bacteria, fungi, and arbuscular mycorrhizal fungi. Then, various factors affecting tea rhizosphere microorganisms were studied, including: endogenous factors, environmental factors, and agronomic practices. Finally, the functions of rhizosphere microorganisms were analyzed, including (a) promoting the growth and quality of tea trees, (b) alleviating biotic and abiotic stresses, and (c) improving soil fertility. Finally, we highlight the gaps in knowledge of tea rhizosphere microorganisms and the future direction of development. In summary, understanding rhizosphere microbial interactions with tea plants is key to promoting the growth, development, and sustainable productivity of tea plants.

Herbal combinations against COVID-19: A network pharmacology, molecular docking and dynamics study.

OBJECTIVE: The aim of this study is to identify molecules from traditional Chinese medicine (TCM) with potential activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. METHODS: We applied the Apriori algorithm to identify important combinations of herbs in the TCM prescriptions for the treatment of coronavirus disease 2019 (COVID-19). Then, we explored the active components and core targets using network pharmacology. In addition, the molecular docking approach was performed to investigate the interaction of these components with the main structural and non-structural proteins, as well as the mutants. Furthermore, their stability in the binding pockets was further evaluated with the molecular dynamics approach. RESULTS: A combination of Amygdalus Communis Vas., Ephedra Herba and Scutellaria baicalensis Georgi was selected as the important herbal combination, and 11 main components and 20 core targets against COVID-19 were obtained. These components, including luteolin, naringenin, stigmasterol, baicalein, and so on, were the potentially active compounds against COVID-19. The binding affinity of these compounds with the potential targets was as high as the positive controls. Among them, baicalein could interfere with multiple targets simultaneously, and it also interfered with the interaction between spike protein and angiotensin-converting enzyme 2 receptor. Additionally, almost all the systems reached stability during dynamics simulation. CONCLUSION: The combination of A. communis, Ephedra Herba and S. baicalensis was the most important herbal combination for the treatment of COVID-19. Baicalein may be a potential candidate against SARS-CoV-2 and its variants. Please cite this article as: Song JB, Zhao LQ, Wen HP, Li YP. Herbal combinations against COVID-19: A network pharmacology, molecular docking and dynamics study. J Integr Med. 2023;21(6):593-604.

Comparative efficacy of Chinese herbal injections for treating endometrial carcinoma: A Bayesian network meta-analysis.

BACKGROUND: In view of the limitations of chemotherapy (CT) for endometrial carcinoma (EC) and the extensive use of Chinese herbal injections (CHIs), this network meta-analysis (NMA) compared the efficacy and safety of 6 CHIs combined with CT for EC. METHODS: Several electronic databases were searched for randomized controlled trials (RCTs). The retrieval period was from the establishment of the databases to September 18, 2022. The quality of the literature was assessed after data extraction using Review Manager version 5.4. The Stata 13.1 and OpenBUGS3.2.3 software were used for data analysis. Cluster analysis was performed to compare the effect of CHIs between 2 different outcomes. RESULTS: A total of 25 RCTs with 2023 patients were included. The findings demonstrated that when combined with CT, Aidi, Compound Kushen, Kangai, Eshuyou injection, and Shenmai injection can increase clinical efficacy compared to chemotherapy alone. The KPS level can be raised with aidi injection. Combining CT with injections of Aidi, Shenmai, Huangqi, and Compound Kushen can improve immunological performance. Combining CT with injections of Aidi, Huangqi, and Compound Kushen can lower serum amounts of tumor markers. Kangai injection was regarded as a good option for minimizing negative responses. According to the cluster analysis, the clinical effective rate, the KPS score, the level of CA125, and the clinical effective rate of Kangai injection and Aidi injection combined with CT were all better. CONCLUSION: Current evidence revealed that CHIs combined with CT have a better impact on patients with EC than CT alone. It's possible that KangAi, Aidi, and Eshuyou infusion are the best CHIs for EC. Additionally, more high-quality RCTs are required in order to further corroborate the findings due to NMA's limitations.

Discharge dynamics of agricultural diffuse pollution under different rainfall patterns in the middle Yangtze river.

Rainfall plays a crucial role in influencing the loss of agricultural diffuse pollution. The middle Yangtze River region is well-know for its humid climate and numerous agricultural activities. Thus, this study quantitatively analyzed the concentration and distribution of nitrogen (N) and phosphorus (P) load and loss in a major tributary of the middle Yangtze River under different rainfall patterns by using sampling analysis and SWAT model simulation. The total nitrogen (TN) and nitrate-nitrogen (NO3-) concentrations were 1.604-3.574 and 0.830-2.556 mg/L, respectively. The total phosphorous (TP) and Soluble Reactive Phosphorus (SRP) were 2-148 and 2-104 µg/L, respectively. The modeling results demonstrated that higher rainfall intensity led to greater load and loss flux of diffuse pollutant at the outlet. Organic nitrogen (ORGN) is the main nitrogen form transported from the subbasin to the reach, while organic phosphorus (ORGP) and inorganic phosphorus (INORGP) were transported at similar amounts. Under the condition of conventional rainfall, the outlet reaches mainly transported NO3-, and ORGN gradually increased when rainstorm events occurred. The ratio of INORGP to ORGP was relatively stable. During extreme rainfall event, rainfall is the dominant element of agricultural diffuse pollution. A strong positive correlation exists between rainfall intensity and pollution loss during rainstorms. Storm rain events were the main source of TN and TP losses. Few storm rain days generated pollutants that accounted for a large proportion of the total loss, and their impact on TP loss was significantly greater than that of TN. The influence of storm rain on TN is mainly the increase in runoff, while TP is sensitive to the runoff and sediment transport promoted by rainfall. By setting different precipitation scenarios, it was confirmed that under the same rainfall amount, short-term storm rain has the most significant impact on the TN load, whereas TP load may be influenced more by the combined effects of rainfall duration and intensity. Therefore, to reduce the impact of agricultural diffuse pollution, it is important to take targeted measures for the rainstorm days.

Real-World Study on Chai-Shi-Jie-Du Granules for the Treatment of Dengue Fever and the Possible Mechanisms Based on Network Pharmacology.

Objectives: Traditional Chinese medicine (TCM) is a widely used method for treating dengue fever in China. TCM improves the symptoms of patients with dengue, but there is no standard TCM prescription for dengue fever. This real-world study aimed to evaluate the effects of Chai-Shi-Jie-Du (CSJD) granules for the treatment of dengue fever and the underlying mechanisms. Methods: We implemented a multicenter real-world study, an in vitro assay and network pharmacology analysis. Patients from 5 hospitals in mainland China who received supportive western treatment in the absence or presence of CSJD were assigned to the control and CSJD groups between 1 August and 31 December 2019. Propensity score matching (PSM) was performed to correct for biases between groups. The clinical data were compared and analyzed. The antidengue virus activity of CSJD was tested in Syrian baby hamster kidney (BHK) cells using the DENV2-NGC strain. Network pharmacological approaches along with active compound screening, target prediction, and GO and KEGG enrichment analyses were used to explore the underlying molecular mechanisms. Results: 137 pairs of patients were successfully matched according to age, sex, and the time from onset to presentation. The time to defervescence (1.7 days vs. 2.5 days, P < 0.05) and the disease course (4.1 days vs. 6.1 days, P < 0.05) were significantly shorter in the CSJD group than those in the control group. CSJD showed no anti-DENV2-NGC virus activity in BHK cells. Network pharmacology analysis revealed 108 potential therapeutic targets, and the top GO and KEGG terms were related to immunity, oxidative stress response, and the response to lipopolysaccharide. Conclusions: CSJD granules exhibit high potential for the treatment of dengue fever, and the therapeutic mechanisms involved could be related to regulating immunity, moderating the oxidative stress response, and the response to lipopolysaccharide.

Polyketides with Anti-Inflammatory Activity from Trichoderma koningiopsis, a Rhizosphere Fungus from the Medicinal Plant Polygonum paleaceum.

Twelve new fungal polyketides, koningiopisins I-P (1-8) and trichoketides C-F (9-12), together with six known congeners (13-18), were isolated from Trichoderma koningiopsis, a rhizosphere fungus obtained from the medicinal plant Polygonum paleaceum. Their structures and absolute configurations were established by spectroscopic analysis, single-crystal X-ray diffraction, the modified Mosher's method, chemical derivatization, the octant rule, and 13C NMR and ECD calculations. Compounds 1-5 are tricyclic polyketides possessing an octahydrochromene framework with a 6,8-dioxabicyclo[3.2.1]octane core. Compounds 7 and 8 contain a unique ketone carbonyl group at C-7 and differ from other members of this group of compounds with the ketone carbonyl group at C-1. Compounds 1, 2, and 13 showed inhibitory activity on LPS-induced BV-2 cells on NO production with IC50 values of 14 ± 1, 3.0 ± 0.5, and 8.9 ± 2.7 µM, respectively.

Rapid identification of chemical compositions from three species of Siegesbeckiae Herba by ultra-performance liquid chromatography-electrospray ionization-quadrupole time of flight-mass spectrometry in combination with deoxyribonucleic acid barcoding.

Siegesbeckiae Herba, a traditional Chinese medicine, originates from Siegesbeckia orientalis, S. glabrescens, and S. pubescens in the Pharmacopoeia of the People's Republic of China. However, accurate identification of decoction pieces from the three plants remains a challenge. In this study, 26 batches of Siegesbeckiae Herba were identified by deoxyribonucleic acid barcoding, and their chemical compositions were determined using ultra-performance liquid chromatography-electrospray ionization-quadrupole time of flight-mass spectrometry. The results showed that the internal transcribed spacer 2 and internal transcribed spacer 1-5.8 S- internal transcribed spacer 2 sequences could distinguish three species. In total, 48 compounds were identified including 12 marker compounds screened for three species using the partial least square discriminant analysis. Among these, two diterpenoids 16-O-malonylkirenol and 15-O-malonylkirenol, and a novel diterpenoid 15,16-di-O-malonylkirenol were isolated and identified. A convenient method for the identification of Siegesbeckiae Herba was established using kirenol and 16-O-acetlydarutoside as control standards by thin-layer chromatography. Unexpectedly, none of the batches of S. orientalis contained kirenol, which did not meet the quality standards of Siegesbeckiae Herba, suggesting that the rationality of kirenol as a quality marker for S. orientalis should be further investigated. The results of this study will contribute to the quality control of Siegesbeckiae Herba.

Characterization of the key odor-active compounds in different aroma types of Fu brick tea using HS-SPME/GC-MSO combined with sensory-directed flavor analysis.

Fu brick tea (FBT) is popular for its unique 'fungal flower' aroma, however, its key odor-active compounds are essentially unknown. In this study, the odor-active compounds of "stale-fungal" aroma (CJX), "fresh-fungal" aroma (QJX), and "fermentation-fungal" aroma (FJX) types FBT were extracted and examined by headspace solid phase microextraction (HS-SPME) combined with gas chromatography-mass spectrometry (GC-MS) and gas chromatographyolfactometry (GC-O). A total of 43 volatile and 38 odor-active compounds were identified by these methods. Among them, the content of dihydroactindiolide (4596-13189 µg/L), (E)-linalool oxide (2863-6627 µg/L), and benzyl alcohol (4992-6859 µg/L) were highest. Aroma recombination experiments further verified that these odor-active compounds could be simulated the overall aroma profile of FBT successfully. Furthermore, omission experiments confirmed that 15, 20, and 15 key odor-active compounds in CJX, QJX, and FJX FBT, respectively. This study will provide a theoretical basis for comprehensively understanding the formation of characteristic aromas in FBT.

The colonic metabolism differences of main alkaloids in normal and colitis mice treated with Coptis chinensis Franch. and Sophora flavescens Ait. herbal pair using liquid chromatography-high resolution mass spectrometry method combined with chemometrics.

Coptis chinensis Franch. and Sophora flavescens Ait. is a herbal pair frequently used in treating ulcerative colitis. However, the bio-disposition profile of the major components in the inflamed gut remains unclear, which is essential to understand the pharmacological material basis of this herb pair. Here we established an integral quantitative and chemometric method to deduce the colonic metabolism differences of this herbal pair in normal and colitis mice. With this LC-MS method, a total of 41 components have been found in the Coptis chinensis Franch. and Sophora flavescens Ait. extract, and 28 metabolites were found in the colon after oral administration. Alkaloid and its phase I metabolites were the main components in the colon of normal and colitis mice. The results of principal component analysis at 6 h after oral administration showed significant colonic metabolism differences between normal and colitis mice. Heamap results showed that colitis induced significant changes in the colonic bio-disposition of this herbal pair extract. In particular, in the context of colitis, the phase I metabolism of berberine, coptisine, jatrorrhizine, palmatine,and epiberberine has been inhibited. These results may provide a basis for understanding the pharmacological material basis of Coptis chinensis Franch. and Sophora flavescens Ait. in treating ulcerative colitis.

Interaction between major catechins and umami amino acids in green tea based on electronic tongue technology.

Umami amino acids inhibit the bitter and astringent taste presentation of catechins, which is essential for the taste regulation of green tea. In this study, the concentration-intensity trends and taste threshold properties of major catechin monomers were investigated using an electronic tongue. The taste and chemical structure interactions between the ester-type catechins and theanine, glutamic acid (Glu), and aspartic acid (Asp) were further analyzed by in vitro simulation and analysis of their reciprocal chemical structures. The results showed that the bitterness and astringency of the major catechin monomers increased with increasing concentration, and their bitterness thresholds and their electron tongue response values were higher than those of the astringent values, while the bitterness and astringency of the ester-type catechins were higher than those of the nonester type. The three amino acids inhibited the bitterness intensity of ester catechins (epigallocatechin gallate, epicatechin gallate, and gallocatechin gallate) at different concentrations, and the effects on the astringency intensity of ester catechins were complicated. Ester catechins significantly enhanced the umami intensity of theanine, Glu, and Asp at different concentrations. Their reciprocal chemical structures showed that hydrogen bonding was the main interaction force between the three ester-type catechins and the umami amino acids, with theanine and Glu interacting more strongly with ester-type catechins than Asp, and Glu having a lower binding energy to ester-type catechins, which bonded more easily.

Multiple stimulus-response berberine plus baicalin micelles with particle size-charge-release triple variable properties for breast cancer therapy.

OBJECTIVE: The aim was to develop a nanoscale drug delivery system with enzyme responsive and acid sensitive particle size and intelligent degradation aiming to research the inhibitory effect on breast cancer. SIGNIFICANCE: The delivery system addressed the problems of tissue targeting, cellular internalization, and slow drug release at the target site, which could improve the efficiency of drug delivery and provide a feasible therapeutic approach for breast cancer. METHODS: The acid sensitive functional material DSPE-PEG2000-dyn-PEG-R9 was synthesized by Michael addition reaction. Then, the berberine plus baicalin intelligent micelles were prepared by thin-film hydration. Subsequently, we characterized the physical and chemical properties of berberine plus baicalin intelligent micelles, evaluated its anti-tumor effects in vivo and in vitro. RESULTS: The target molecule was successfully synthesized, and the intelligent micelles showed excellent chemical and physical properties, delayed drug release and high encapsulation efficiency. In vitro and in vivo experiments also confirmed that the intelligent micelles could effectively target tumor sites, penetrate tumor tissues, enrich in tumor cells, inhibit tumor cell proliferation, inhibit tumor cell invasion and migration, and induce tumor cell apoptosis. CONCLUSION: Berberine plus baicalin intelligent micelles have excellent anti-tumor effects and no toxicity to normal tissues, which provides a new potential drug delivery strategy for the treatment of breast cancer.