The Beneficial Effects of Dietary Astragali Radix Are Related to the Regulation of Gut Microbiota and Its Metabolites.

Astragali Radix (AR) or its extract has been used as an herbal medicine and dietary supplement in China, Europe, and the United States. The gut microbiota could provide new insights for exploring dietary supplements' underlying mechanism on organisms. However, no reports have focused on the regulatory effect of AR on the gut microbiota as a dietary supplement. In this study, healthy ICR mice of either sex were divided into AR and control (CON) groups and given AR water extract (4.55 mg/kg·day-1) or saline by gavage for 14 days, respectively. Then 16S rRNA gene sequencing and ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry-based fecal metabolomics were integrated to investigate the benefits of dietary AR. Weighted gene coexpression network analysis was also introduced to investigate the metabolites with highly synergistic changes. AR supplementation influenced the structure of intestinal microflora, especially enriching short-chain fatty acid-producing bacteria g_Coprobacillus, g_Prevotella, and g_Parabacteroides. AR also significantly altered the fecal metabolome, mainly related to amino acid metabolism, nucleotide metabolism, and bile acid (BA) metabolism. Moreover, the increased secondary BAs and BA-sulfates might closely relate to intestinal microflora. These findings provide valuable insights for future research of dietary AR as a functional food.

Effects of Flavonoid Supplementation on Athletic Performance in Healthy Adults: A Systematic Review and Meta-Analysis.

Flavonoids, known for their antioxidant properties, can prevent reactive oxygen species (ROS) and influence athletic performance through various physiological and metabolic mechanisms. However, there are conflicting results after summarizing and analyzing the relevant literature. Hence, it is warranted to evaluate the overall impact of flavonoids on athletic performance in healthy adults based on a comprehensive and systematic review and meta-analysis. After searching four databases for literature published since their respective establishments until February 2023 and conducting publication bias and quality assessments, a total of 22 studies were ultimately included. The names and doses of flavonoids, various outcome measurements, as well as types of training, were extracted from included studies. The athletic performance outcomes from the included studies were categorized into 'performance tests' and 'exercise tolerance,' depending on the type of training undertaken. Several statistical results, such as pooled effect size (ES), among others, were implemented by meta-analysis using the random effects model. The results of meta-analysis suggest that there is currently sufficient evidence (ES = -0.28; 95% confidence interval (CI): [-0.50, -0.07]; p = 0.01 and ES = 0.23; 95% CI: [0.07, 0.39]; p = 0.005) to support the notion that flavonoid supplementation enhanced athletic performance in performance tests and exercise tolerance. In addition, among the subgroups, nonsignificant results were observed for athletes (p = 0.28) and acute supplementation (p = 0.41) in performance tests, as well as athletes (p = 0.57) and acute supplementation (p = 0.44) in exercise tolerance. Meanwhile, significant results were found for non-athletes (p = 0.04) and long-term supplementation (p = 0.02) in performance tests, as well as non-athletes (p = 0.005) in performance tests and long-term supplementation (p = 0.006) in exercise tolerance. The nonsignificant results were likely due to the limitation in the number of related papers, sample sizes, optimal dosage, duration, type of flavonoids, and other factors. Therefore, future research should focus on further investigating these relationships with larger sample sizes, optimal dosage, duration, and type of flavonoids to provide more robust conclusions.

Black soldier fly pulp in the diet of golden pompano: Effect on growth performance, liver antioxidant and intestinal health.

Black soldier fly (Hermetia illucens) has been widely researched as a protein source for fish meal replacement in aquaculture, but few studies have focused on its potential as a feed additive for growth and immune enhancement. We conducted a 56-day culture experiment to determine the impact of feed addition of black soldier fly pulp (BSFP, with 86.2% small peptides in dry basis) on growth performance, plasma biochemistry, liver antioxidant levels, intestinal immunity, digestion and microbiota of juvenile golden pompano (Trachinotus ovatus, 5.63 ± 0.02 g). BSFP was added to the basal diet at 0%, 1%, 3%, 5%, 7% and 9% (named Control, BSFP-1, BSFP-3, BSFP-5, BSFP-7, BSFP-9), respectively. BSFP increased the weight gain rate, specific growth rate, protein efficiency ratio and reduced the feed conversion rate of juvenile T. ovatus, the optimal growth performance was reached at BSFP-1, after which a negative feedback phenomenon was observed. Low levels of BSFP upregulated the expression of hepatic antioxidant, intestinal tight junctions, anti-inflammatory related genes and enhanced antioxidant, immune and intestinal digestive enzyme activities, which simultaneously reduced hepatic malondialdehyde and plasma aspartate transaminase and alanine aminotransferase concentrations. However, at BSFP-7, catalase activity was significantly reduced, while NF-κB p65 and pro-inflammatory cytokines transcription was significantly enhanced (P < 0.05). The results suggest that high doses of BSFP addition may damage fish health by inhibiting small peptide uptake, decreasing the activity of antioxidant enzyme and activating the canonical NF-κB pathway. Conversely, low doses of BSFP enhanced intestinal tight junction protein transcription, digestive enzyme activity and immune performance, inhibited pathogenic microbiota, while enhancing liver antioxidant capacity, which was associated with activated Nrf2-Keap1 pathway and suppressed NF-κB pathway, showing its potential as a feed additive to aquafeeds.

Efficacy and safety of Xiao-ai-ping injection add-on therapy to chemotherapy in patients with non-small cell lung cancer: A systematic review and meta-analysis.

BACKGROUND: Xiao-ai-ping injection (XAPI) combined with chemotherapy has potential efficacy and less side effects in the treatment of non-small cell lung cancer (NSCLC). At present, there are many clinical studies on XAPI combined with chemotherapy in the treatment of NSCLC, but the results are different. The purpose of this study was to evaluate the efficacy and safety of XAPI combined with chemotherapy in the treatment of NSCLC by meta-analysis system. METHODS: The databases to be searched include PubMed, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang database, Chinese Scientific Journal Database, and so on. In addition, relevant journals and magazines will manually search in various fields as supplements. The search date is set from the establishment of the database until July 8, 2023. The 2 researchers will use Endnote X9 software for literature screening and data extraction and independently evaluate the quality. We then assessed the quality and risk of inclusion in the study and observed outcome indicators. RESULTS: A total of 28 trials were included in this study, 1947 patients with NSCLC (974 receiving XAPI combined chemotherapy and 973 receiving chemotherapy alone). The results of meta-analysis showed that: Objective tumor response rate of NSCLC (P < .00001). Improvement in Karnofsky performance score of NSCLC (P < .00001). Quality of life score of NSCLC (P < .00001). The result of CD3 + (P < .00001). The result of CD4 + (P < .00001). The result of CD8 + (P < .00001). The result of CD4+/CD8 + (P = .0001). Leukopenia (P < .00001). Thrombocytopenia (P < .00001). Hemoglobin decrease (P < .00001). Liver function (P = .04). Nausea and vomiting (P < .00001). CONCLUSION: Our meta-analyses demonstrated that XAPI adjunct with chemotherapy can improve the patient quality of life, reduce adverse reactions, and enhanced immune function, the treatment is effective and high safety. Which suggests that it might be used for NSCLC. However, a large sample of randomized controlled trials are needed to further study the long-term efficacy of XAPI.

Ginkgolide C attenuates cerebral ischemia/reperfusion-induced inflammatory impairments by suppressing CD40/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. (Ginkgoaceae), a traditional Chinese medicine, has been applied for thousands of years for the treatment of cardio-cerebral vascular diseases in China. It is written in Compendium of Materia Medica that Ginkgo has the property of "dispersing poison", which is now referred to as anti-inflammatory and antioxidant. Ginkgolides are important active ingredients in Ginkgo biloba leaves and ginkgolide injection has been frequently applied in clinical practice for the treatment of ischemic stroke. However, few studies have explored the effect and mechanism of ginkgolide C (GC) with anti-inflammatory activity in cerebral ischemia/reperfusion injury (CI/RI). AIM OF THE STUDY: The present study aimed to demonstrate whether GC was capable of attenuating CI/RI. Furthermore, the anti-inflammatory effect of GC in CI/RI was explored around the CD40/NF-κB pathway. MATERIALS AND METHODS: In vivo, middle cerebral artery occlusion/reperfusion (MCAO/R) model was established in rats. The neuroprotective effect of GC was assessed by neurological scores, cerebral infarct rate, microvessel ultrastructure, blood-brain barrier (BBB) integrity, brain edema, neutrophil infiltration, and levels of TNF-α, IL-1ß, IL-6, ICAM-1, VCAM-1, and iNOS. In vitro, rat brain microvessel endothelial cells (rBMECs) were preincubated in GC before hypoxia/reoxygenation (H/R) culture. The cell viability, levels of CD40, ICAM-1, MMP-9, TNF-α, IL-1ß, and IL-6, and activation of NF-κB pathway were examined. In addition, the anti-inflammatory effect of GC was also investigated by silencing CD40 gene in rBMECs. RESULTS: GC attenuated CI/RI as demonstrated by decreasing neurological scores, reducing cerebral infarct rate, improving microvessel ultrastructural features, ameliorating BBB disruption, attenuating brain edema, inhibiting MPO activity, and downregulating levels of TNF-α, IL-1ß, IL-6, ICAM-1, VCAM-1, and iNOS. Coherently, in rBMECs exposed to H/R GC enhanced cell viability and downregulated levels of ICAM-1, MMP-9, TNF-α, IL-1ß, and IL-6. Furthermore, GC suppressed CD40 overexpression and hindered translocation of NF-κB p65 from the cytosol to the nucleus, phosphorylation of IκB-α, and activation of IKK-ß in H/R rBMECs. However, GC failed to protect rBMECs from H/R-induced inflammatory impairments and suppress activation of NF-κB pathway when CD40 gene was silenced. CONCLUSIONS: GC attenuates cerebral ischemia/reperfusion-induced inflammatory impairments by suppressing CD40/NF-κB pathway, which may provide an available therapeutic drug for CI/RI.

Quality assessment of Astragali Radix based on pseudo-targeted metabolomics and chemometric approach.

Astragali Radix is widely used because of its dual use in medicine and food, and its quality evaluation is of great importance. In this study, a pseudo-targeted metabolomics approach based on scheduled multiple reaction monitoring was developed, and a total of 114 compounds with good linearity, sensitivity, and reproducibility were selected for relative quantification, and the chemical differences between Astragali Radix of different growth patterns were further compared by chemometric analysis. With the help of multivariate and univariate analysis, 26 differential compounds between wild/semi-wild Astragali Radix and cultivated Astragali Radix were determined. Then five marker compounds were screened out by lasso regression, and further verified by systematic clustering, random forest, support vector machine, and logistic regression. In addition, malonyl-substituted flavonoids showed relatively higher content in wild/semi-wild Astragali Radix. Thus, the malonyl substitution was characteristic for flavonoids in wild/semi-wild Astragali Radix. In conclusion, the application of pseudo-targeted metabolomics and various statistical methods could offer multi-dimensional information for the holistic quality evaluation of Astragali Radix.

[Toxicity comparison of raw and vinegar-processed Bupleuri Radix based on ~1H-NMR metabolomics].

This study compared the toxicity of raw Bupleuri Radix(BR) and vinegar-processed Bupleuri Radix(VPBR) based on proton nuclear magnetic resonance(~1H-NMR), and explored the mechanism of toxicity. Thirty-two male Sprague-Dawley(SD) rats were randomly divided into four groups: a control group(distilled water), a raw BR group(15 g·kg~(-1)·d~(-1)), a rice VPBR(R-VPBR) group(15 g·kg~(-1)·d~(-1)), and a shanxi VPBR(S-VPBR) group(15 g·kg~(-1)·d~(-1)). After administration for 30 d, pathological sections were treated and observed, and biochemical indexes related to liver and renal function were determined. The serum, liver, and kidney of rats were collected and analyzed by ~1H-NMR. The principal component analysis(PCA) and orthogonal partial least squares-discrimination analysis(OPLS-DA) were performed. The results showed that, as compared with the control group, alanine aminotransferase(ALT), aspartate aminotransferase(AST), and alkaline phosphatase(ALP) in the raw BR group were increased significantly, while ALT and ALP in the R-VPBR and S-VPBR groups were significantly decreased(P<0.05), which indicated that BR showed certain hepatotoxicity, and vinegar processing reduced its hepatotoxicity. No significant difference of blood urea nitrogen(BUN) and creatinine(CREA), the biochemical indexes related to renal function, was observed in the control group and administration groups, indicating that BR had less effect on the renal function. The results of multivariate statistical analysis showed that the biomarkers of BR affecting liver metabolism were methionine, glutamine, and glutamic acid, and affecting kidney metabolism were taurine, ornithine, and inosine. These biomarkers were mainly involved in amino acid metabolism, energy metabolism, lipid metabolism, and taurine metabolism. VPBR alleviated the effect on the biomarkers, and S-VPBR had smaller effect than R-VPBR. Combining the results of biochemical indexes and metabolomics analysis, both raw BR and VPBR showed toxic effect on rats, whereas vinegar processing reduced its toxicity. S-VPBR has smaller effect on kidney and liver metabolism than R-VPBR, which indicates that the vinegar used for processing has certain effect on the toxicity of BR.

Image fusion technique for target volume delineation in 125I seed implant brachytherapy for parotid gland cancers.

Purpose: Variability in volume delineation is a possible error source in brachytherapy. This study assessed the interobserver variations in clinical target volume (CTV) delineation in postoperative adjuvant 125I seed implant brachytherapy after parotid gland cancer surgical resection and evaluated the image fusion technique for target volume delineation. Material and Methods: Five radiation oncologists delineated gross tumor volume (GTV) and CTV in 20 patients using conventional delineation and image fusion methods. The consistency in target volume delineation was determined on the basis of differences between the oncologists. Variability was determined using Kendall's W-test, the mean conformity index (CI), the mean distance to conformity (MDC), and the center of gravity distance (CGD). Results: There were significant variations in the delineated target volumes among radiation oncologists, but the CTV consistency was significantly enhanced using the image fusion technique, based on Kendall's W, mean CI, average MDC, and average CGD, which were 0.752, 0.41, 2.75, and 4.997, respectively, using the conventional method, and 0.987, 0.86, 0.55, and 1.27, respectively, using the image fusion method. Conclusions: The interobserver variation in the delineation of the postoperative parotid target volume is large, but it can be considerably decreased using image fusion technology, which resulted in a noticeable improvement in the delineation precision of the target volume for parotid gland cancer. Thus, this technology can enhance the efficacy of 125I seed implant brachytherapy and decrease any adverse effects induced by errors in target delineation.

Investigating the inter-individual variability of Astragali Radix against cisplatin-induced liver injury via 16S rRNA gene sequencing and LC/MS-based metabolomics.

BACKGROUND: Cisplatin (CDDP), one of the widely used chemotherapeutic drugs, can induce a series of side effects, such as hepatotoxicity and gastrointestinal toxicity. Astragali Radix (AR) is widely used as the tonic herbal medicine in traditional Chinese medicine (TCM). However, there was no report about the hepatoprotective effect of AR against the cisplatin-induced hepatic damage. PURPOSE: This study aimed to investigate the protective effect and potential mechanism of AR water extract against the cisplatin-induced liver injury. METHODS: Cisplatin was utilized to induce the liver injury using ICR mice, and the protective effect of AR was evaluated by serum biochemistry indices and liver histopathology. Then UHPLC Q-TOF-MS/MS-based untargeted serum metabolomics approach combined with 16S rRNA-based microbiota analysis was used to explore the underlying biomarkers and mechanism about the liver-protective effect of AR. RESULTS: AR could decrease the serum AST and ALT, ameliorate hepatic pathological damages caused by cisplatin. Serum metabolomics indicated AR could regulate the biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, purine metabolism, and fatty acid biosynthesis. In addition, 16S rRNA gene sequencing analysis showed that AR could regulate cisplatin-induced gut microbiota disorder, especially the inflammation-related bacteria (p_Deferribacteres, g_Enterococcus, and g_Alistipes, etc.), and the short chain fatty acids (SCFAs)-producing bacteria (g_Alloprevotella, g_Intestinimoas, and g_Flavonifractor). Moreover, 7 mice (AR-7) showed better liver protective effect than the other 3 mice (AR-3), and their regulatory effect on the gut microbiota and serum metabolites were also different, indicating the presence of inter-individual variability for the liver protective effect of AR. CONCLUSIONS: This study revealed the protective effect and the potential mechanisms of AR against cisplatin-induced liver injury, and found that inter-individual variability of the liver protective effect of AR was related to the host microbiome and metabolome. These findings provided new insight into the health effect of dietary AR as a functional food for cisplatin-based chemotherapy.

Astragali Radix-Codonopsis Radix-Jujubae Fructus water extracts ameliorate exercise-induced fatigue in mice via modulating gut microbiota and its metabolites.

BACKGROUD: Astragali Radix (AR) and Codonopsis Radix (CR) are widely used as the tonic herbal medicine with efficacy of tonifying qi in traditional Chinese medicine (TCM), which showed significant antifatigue activities. In this study, AR and CR were combined, with Jujubae Fructus (JF) further added to improve the taste, to afford the ACJ extracts in the ratio of 2:1:2. RESULTS: The results showed that ACJ water extract exhibited antifatigue effect by the weight-loaded exhaustive swimming test in mice. The untargeted fecal metabolomic approach and 16S rRNA gene sequencing analysis showed that ACJ could improve exercise performance by regulating changes of gut metabolites and microbiota to alleviate fatigue. Four pathways were determined as the key pathways relating with its antifatigue effect, which included sphingolipid metabolism, glycerophospholipid metabolism, valine, leucine and isoleucine biosynthesis and d-arginine and d-ornithine metabolism. Correlation analysis showed the complex association among bacteria, metabolites and phenotypes. CONCLUSION: In conclusion, this study revealed new perspectives to study the antifatigue mechanism of ACJ extracts from the gut microbiota, which provided the basis for further functional food development. © 2022 Society of Chemical Industry.

Study of the Unique Characteristics of Multi-Elements of the Wild Astragali Radix from Shanxi Province by Inductively Coupled Plasma Mass Spectrometry.

BACKGROUND: Astragali Radix (AR) is widely used because of its dual use in medicine and food. Wild Astragali Radix from Hunyuan county of Shanxi province in China is accepted as a geo-authentic medicine with high quality and good medicinal effects. Multi-elements of Astragali Radix partially reflect its efficacy and safety. However, there has been no systemic research about the elemental analysis of geo-authentic Astragali Radix until now. OBJECTIVE: In this paper, multi-elemental profiling of Astragali Radix from Gansu, Jilin, Inner Mongolia, Shaanxi and Shanxi provinces in China was carried out. METHODS: A microwave digestion coupled with inductively coupled plasma-MS (ICP-MS), principal component analysis (PCA), and partial-least square-discriminate analysis (PLS-DA) were used for analysis of the unique elemental accumulation ability of Shanxi wild AR. RESULTS: Compared to the samples from Gansu, Jilin, Inner Mongolia, Shaanxi provinces, and the cultivated samples from Shanxi, for 53 stably detected elements, the concentrations of most elements (Ba, Cs, Ga, La, Pr, and so on) were significantly higher while a few (Cd, Cu, P, W and Zn) were significantly lower in wild Astragali Radix from Shanxi. After binary logistic regression, combinational variable Ba-P was found to be a good marker to distinguish wild Astragali Radix of Shanxi province from the samples with other origins, and the total positive prediction probability of the test samples, both bought from the market and gathered from their original field, could reach 93.8% through external validation using the model. CONCLUSION: Multi-elemental analysis coupled with PCA, PLS-DA, nonparametric analysis and binary logistic regression can be a good tool for the identification of wild Astragali Radix from Shanxi province. HIGHLIGHTS: An ICP-MS method was developed and validated for multi-elements. Fifty-three elements in Astragali Radix from samples with different origins were compared. The wild Astragali Radix from Shanxi had unique elemental characteristics. Combinational variable Ba-P is a good marker to identify wild AR from Shanxi.

Synthesis of Silver Nanoparticles from the Polysaccharide of Farfarae Flos and Uncovering Its Anticancer Mechanism Based on the Cell Metabolomic Approach.

In this study, the polysaccharide of Farfarae Flos (FFP) was utilized as a reducing agent to the green synthesis of FFP@AgNPs, and the anticancer activity was evaluated using the HT29 cells. The results showed that the FFP@AgNPs could significantly decrease proliferation ability, inhibit migration, and promote cell apoptosis of HT29 cells, which suggested that the FFP@AgNPs showed significant, strong cytotoxicity against HT29 cells. The cell metabolomic analysis coupled with the heatmap showed an obvious metabolome difference for the cells with and without FFP@AgNPs treatment, which was related to 51 differential metabolites. Four metabolic pathways were determined as the key pathways, and the representative functional metabolites and metabolic pathways were validated in vitro. Nicotinic acid (NA) was revealed as the key metabolite relating with the effect of FFP@AgNPs, and it was interesting that NA supplementation could inhibit the proliferation ability of HT29 cells in vitro, lead to mitochondrial dysfunction, reduce intracellular ATP, and damage the integrity of the cell membrane, which exhibited a similar effect as FFP@AgNPs. In conclusion, this study not only revealed the anticancer mechanism of FFP@AgNPs against the HT29 cells but also provided the important reference that NA shows a potential role in the development of a therapy for colorectal cancer.

[Multiple components of Mahuang Shengma Decoction on prevention and treatment of acute lung injury based on RAGE/NF-κB signaling pathway].

To investigate the potential molecular markers and drug-compound-target mechanism of Mahuang Shengma Decoction(MHSM) in the intervention of acute lung injury(ALI) by network pharmacology and experimental verification. Databases such as TCMSP, TCMIO, and STITCH were used to predict the possible targets of MHSM components and OMIM and Gene Cards were employed to obtain ALI targets. The common differentially expressed genes(DEGs) were therefore obtained. The network diagram of DEGs of MHSM intervention in ALI was constructed by Cytoscape 3. 8. 0, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of target genes. The ALI model was induced by abdominal injection of lipopolysaccharide(LPS) in mice. Bronchoalveolar lavage fluid(BALF) was collected for the detection of inflammatory factors. Pathological sectioning and RT-PCR experiments were performed to verify the therapeutic efficacy of MHSM on ALI. A total of 494 common targets of MHSM and ALI were obtained. Among the top 20 key active compounds of MHSM, 14 from Ephedrae Herba were found to be reacted with pivotal genes of ALI [such as tumor necrosis factor(TNF), tumor protein 53(TP53), interleukin 6(IL6), Toll-like receptor 4(TLR4), and nuclear factor-κB(NF-κB)/p65(RELA)], causing an uncontrolled inflammatory response with activated cascade amplification. Pathway analysis revealed that the mechanism of MHSM in the treatment of ALI mainly involved AGE-RAGE, cancer pathways, PI3 K-AKT signaling pathway, and NF-κB signaling pathway. The findings demonstrated that MHSM could dwindle the content of s RAGE, IL-6, and TNF-α in the BALF of ALI mice, relieve the infiltration of inflammatory cells in the lungs, inhibit alveolar wall thickening, reduce the acute inflammation-induced pulmonary congestion and hemorrhage, and counteract transcriptional activities of Ager-RAGE and NF-κB p65. MHSM could also synergically act on the target DEGs of ALI and alleviate pulmonary pathological injury and inflammatory response, which might be achieved by inhibiting the expression of the key gene Ager-RAGE in RAGE/NF-κB signaling pathway and downstream signal NF-κB p65.

Dose-Effect/Toxicity of Bupleuri Radix on Chronic Unpredictable Mild Stress and Normal Rats Based on Liver Metabolomics.

Depression, one of the most prevalent psychiatric diseases, affects the quality of life of millions of people. Studies have shown that the lower polar fraction of Bupleuri Radix (PBR) elicited therapeutic effects in chronic unpredictable mild stress (CUMS) rats. In contrast, comparatively mild liver injury was observed in normal rats administered a high PBR dose. It is essential to clarify the effective and safe dose of PBR and its dose-effect/toxicity relationship. In this study, we used the CUMS model to evaluate the effects and toxicities of PBR and to decipher the dose-effect/toxicity relationship and mechanism using the liver metabonomics combined with multivariate statistical analysis. In CUMS rats, PBR improved the depression-like behaviors including reduced body growth rate, anhedonia, and locomotor activities, and markedly reduced the contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In control rats, PBR treatment altered ALT and AST from typical levels. Moreover, the effective dose range for CUMS rats was 12.6-163 g (herb)/kg, the median toxicity dose for CUMS and normal rats were 388 and 207 g (herb)/kg. The toxicological results showed that the cytokeratin-18 fragment level was increased significantly in CUMS rats given with 100 g (herb)/kg PBR. After a comprehensive analysis, the use of PBR dose was determined to be 12.6-50 g (herb)/kg. In CUMS rats, PBR could reverse amino acid metabolism, energy metabolism, sphingolipid metabolism, and ß-oxidation of fatty acids to produce an anti-depressant effect in a dose-dependent manner. In control rats, two additional metabolic pathways were significantly perturbed by PBR, including glycerophospholipid metabolism and bile acid metabolism. Moreover, the comprehensive metabolic index including dose-effect index (DEI) and dose toxicity index (DTI) had a remarkable ability (ROC = 0.912, ROC = 0.878) to predict effect and toxicity. The DEI and DTI were used to determine the dose range of effect and toxicity which was shown high concordance with previous results. Furthermore, the CUMS rats possessed a higher toxicity tolerance dose of PBR which was consistent with the theory of "You Gu Wu Yun" in traditional Chinese medicine. The metabonomics techniques combined with correlation analysis could be used to discover indicators for comprehensive evaluations of efficacy and toxicity.

Systems biology analysis of the effect and mechanism of total flavonoids of Astragali Radix against cyclophosphamide-induced leucopenia in mice.

This study aimed to demonstrate the pharmacological mechanism of total flavonoids extracted from Astragali Radix (AR) on cyclophosphamide (Cy)-induced leucopenia in mice. First, flow cytometry, network pharmacology and plasma metabolomics were integrated to investigate the pharmacological mechanism of total flavonoids, the targets from network pharmacology and metabolites from metabolomics were analyzed by DAVID. Then, the key cytokines were validated to confirm the predicted metabolic pathway results. The results showed that total flavonoids significantly increased body weight, routine blood indices, bone marrow DNA cells, and also markedly caused lymphocyte proliferation by increasing the percentages of CD4+ and CD8+. Using network pharmacology and metabolomics methods, the study identified 13 signal-related pathways regulated by total flavonoids including PI3K-Akt signaling pathway, Jak-STAT signaling pathway, Sphingolipid signaling pathway, and so on. Total flavonoids also reversed changes in serum cytokines IL-2, IL-6, and GM-CSF. Total flavonoids exhibits protective effects against leucopenia probably by modulating immunologic functions, promoting cell proliferation, and regulating related metabolic pathways at the system level.

Revealing the anti-melanoma mechanism of n-BuOH fraction from the red kidney bean coat extract based on network pharmacology and transcriptomic approach.

Red kidney bean coat (RKBC) extract contains bioactive compounds that are known to exhibit anti-melanoma activity in vitro. However, knowledge on antitumor component and mechanism of RKBC extract has not been fully clarified. Here, RKBC extract was portioned with different solvent sequentially, and based on the cell viability assay, cell migration assay, AO/EB and Hoechst 33342 staining assay, and Annexin V-FITC/PI double staining, n-BuOH (BU) fraction was identified as the most potent antitumor fraction. It exhibited potential anti-melanoma activity via the induction of apoptosis and vacuolization in B16-F10 cells. Transcriptomic and bioprocess-target network analysis revealed that BU fraction triggered apoptosis and vacuolization through regulating PI3K-AKT-FOXO, MDM2-p53 pathway and increasing the expression of Bcl-xl. In addition, quercetin might be served as one of the key anti-melanoma compounds in BU fraction through the similar mechanism. Although the anti-melanoma activity and mechanism of BU fraction have not been elucidated completely, this study effectively expands our understanding for the anti-melanoma activity of RKBC extract and provided the basis for the further functional food research and development using red kidney bean, as well as a new possibility for treating melanoma.

TiO2@HNTs Robustly Decorated PVDF Membrane Prepared by a Bioinspired Accurate-Deposition Strategy for Complex Corrosive Wastewater Treatment.

As industrialization has spread all around the world, the problems of water pollution such as offshore oil spill and industrial sewage discharge have spread with it. Although many new separation materials have been successfully developed to deal with this crisis, a large number of water treatment materials only focus on the treatment of classified single water pollutant under mild conditions. It is a great challenge to treat soluble contaminants such as water-soluble dyes and insoluble contaminants, for example, emulsified oils simultaneously in a strong corrosive environment. Herein, in this work, corrosive resistance and multifunctional surface on a commercial polyvinylidene difluoride (PVDF) membrane via a tunicate-inspired gallic acid-assisted accurate-deposition strategy is created. Owing to the titanium-carboxylic coordination bonding and accurate-deposition strategy, the as-prepared membrane exhibits extraordinary stability, facing various harsh environmental challenges and incredibly corrosive situations (e.g., 4 M NaOH, 4 M HCl, and saturated NaCl solution). The robust multifunctional surface also endows commercial PVDF membrane with the ability for in situ separation and adsorption of surfactant-stabilized oil-in-water (corrosive and dyed) emulsions with high adsorption efficiencies up to 99.9%, separation efficiencies above 99.6%, and permeation flux as high as 15,698 ± 211 L/(m2·h·bar). Furthermore, the resultant membrane can be regenerated facilely and rapidly by flushing a small amount of HCl (4 M) or NaOH (4 M), making the corrosive resistance membrane attain a long-term and high-efficiency application for complex dyed wastewater treatment. Therefore, the multifunctional membrane has a broad application prospect in the industrial field.

Petroleum extract of Farfarae Flos alleviates nasal symptoms by regulating the Th1-Th2 cytokine balance in a mouse model of Allergic Rhinitis.

Farfarae Flos is a traditional Chinese medicine that has long been used to treat allergies. In this study, we aimed to investigate the effect of a petroleum extract of Farfarae Flos (PEFF) in a mouse model of allergic rhinitis (AR) and to explore the underlying molecular mechanisms of action. An animal model of AR was established by sensitization and challenge of BALB/c mice with ovalbumin (OVA). PEFF was administered intranasally and AR nasal symptoms were assessed on a semi-quantitative scale according to the frequencies of nose rubbing and sneezing and the degree of rhinorrhea. The mechanism of action of PEFF was evaluated by histological analysis of nasal mucosa architecture and inflammatory status; ELISA-based quantification of serum OVA-specific IgE, interferon-γ (IFN-γ), and interleukin-4 (IL-4) concentrations; and immunohistochemical and western blot analysis of T-bet and GATA3 protein expression in nasal mucosa and spleen tissues. The results showed intranasal administration of PEFF alleviated AR symptom scores and reduced both the infiltration of inflammatory cells and tissue damage in the nasal mucosa. PEFF significantly decreased serum concentrations of OVA-specific IgE (P<0.01) and IL-4 (P<0.05) and significantly increased IFN-γ (P<0.01). PEFF also upregulated the expression of T-bet protein (P<0.05) but downregulated GATA3 protein (P<0.05) in nasal mucosa and spleen tissues. In conclusion, PEFF effectively reduces AR nasal symptoms and serum IgE levels in a mouse model and may act by correcting the imbalance between Th1 and Th2 responses.

Chemical comparison of the raw and processed Farfarae Flos by liquid chromatography-mass spectrometry based metabolomic approach.

Farfarae Flos (FF) has been used in China for a long time as an anti-tussive and expectorant herbal drugs, and it was usually honey-fried FF (HFF). To clarify the mechanism of honey processing, it is important to know the chemical difference between FF and HFF firstly. In this study, UHPLC-Orbitrap-MS was used to characterize the chemical compounds in FF, honey and HFF. Then the metabolomic approach based on UHPLC-Orbitrap-MS revealed 68 differential compounds between the FF and HFF, and chemical reactions occurring during processing were also proposed to elucidate the honey processing mechanisms of FF. In order to investigate the chemical difference between FF and HFF comprehensively and accurately, the components derived from the honey and the moisture content in FF and HFF were considered for the first time. In summary, this study investigated the chemical differences between FF and HFF in a holistic way, which laid the basis for the quality control of HFF and further explaining the honey processing mechanisms of FF. In addition, eight native compounds derived from the honey could be used as the index to authenticate the HFF prepared by the genuine honey.

Deciphering the correlations between aging and constipation by metabolomics and network pharmacology.

From the points of view of phenomena and experience, aging and constipation are inextricably correlated. However, experimental support and underlying mechanisms are still lacking. The purpose of this study is to explore the relationships between aging and constipation from the perspectives of fecal metabolites and network pharmacology. The behavioral analyses of aging and constipation were carried out on both aging rats and constipation rats. We found that aging rats exhibited not only significant aging behaviors but also significant constipation behaviors, while constipation rats exhibited both significant constipation and aging behaviors. Additionally, fecal metabolomics was carried out and found that 23 metabolites were aging-related and 22 metabolites were constipation-related. Among them, there were 16 differential metabolites in common with 11 metabolic pathways. Network pharmacology was applied to construct the target-pathway network of aging and constipation, revealing that pathway in cancer was the most associated signaling pathway. The current findings will provide not only a novel perspective for understanding aging and constipation, but a theoretical association and understanding the traditional Chinese medicine theory and the Western medicine theory about aging and constipation, as well as support for the clinical research and development of medicine related to constipation in the elderly.