Modified Bushen Yiqi Formula mitigates pulmonary inflammation and airway remodeling by inhibiting neutrophils chemotaxis and IL17 signaling pathway in rats with COPD.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic obstructive pulmonary disease (COPD) is a major global health concern characterized by pulmonary inflammation and airway remodeling. Traditional Chinese medicine, such as Modified Jiawei Bushen Yiqi Formula (MBYF), has been used as a complementary therapy for COPD in China. AIM OF THE STUDY: To investigate the therapeutic potential of MBYF in a rat model of COPD induced by cigarette smoke (CS) exposure and explore the underlying mechanism. MATERIALS AND METHODS: The COPD rat model was established through 24 weeks of CS exposure, with MBYF administration starting in the 9th week. Pulmonary function, histological analysis, inflammatory cell count and molecular assays were employed to assess the effects of MBYF on airway remodeling, pulmonary inflammation, neutrophils chemotaxis and the IL17 signaling pathway. RESULTS: MBYF treatment effectively delayed airway remodeling, as evidenced by improved pulmonary function parameters. Histological examination and bronchoalveolar lavage fluid analysis revealed that MBYF mitigated CS-induced pulmonary inflammation by reducing inflammatory cell infiltration. Pharmacological network analysis suggested that MBYF may act through the IL17 signaling pathway to regulate inflammatory responses. RNA-sequencing and molecular assays indicated that MBYF inhibited neutrophils chemotaxis through downregulating the CXCL1/CXCL5/CXCL8-CXCR2 axis, and suppressed IL17A, IL17F and its downstream cytokines, including IL6, TNFα, IL1ß, and COX2. Furthermore, MBYF inhibited the activation of NF-κB and MAPKs in the IL17 signaling pathway. CONCLUSION: MBYF exhibits potential as an adjunct or alternative treatment for COPD, effectively mitigating CS-induced pulmonary inflammation and airway remodeling through the inhibition of neutrophil chemotaxis and IL17 signaling pathway.

A Review of Healthy Dietary Choices for Cardiovascular Disease: From Individual Nutrients and Foods to Dietary Patterns.

Cardiovascular disease (CVD) remains the first cause of mortality globally. Diet plays a fundamental role in cardiovascular health and is closely linked to the development of CVD. Numerous human studies have provided evidence on the relationship between diet and CVD. By discussing the available findings on the dietary components that potentially influence CVD progression and prevention, this review attempted to provide the current state of evidence on healthy dietary choices for CVD. We focus on the effects of individual macronutrients, whole food products, and dietary patterns on the risks of CVD, and the data from population-based trials, observational studies, and meta-analyses are summarized. Unhealthy dietary habits, such as high intake of saturated fatty acids, sugar-sweetened beverages, red meat, and processed meat as well as high salt intake are associated with the increased risk of CVD. Conversely, increased consumption of plant-based components such as dietary fiber, nuts, fruits, and vegetables is shown to be effective in reducing CVD risk factors. The Mediterranean diet appears to be one of the most evidence-based dietary patterns beneficial for CVD prevention. However, there is still great debate regarding whether the supplementation of vitamins and minerals confers cardioprotective benefits. This review provides new insights into the role of dietary factors that are harmful or protective in CVD, which can be adopted for improved cardiovascular health.

Proteomic analysis reveals the molecular mechanism of Astragaloside in the treatment of non-small cell lung cancer by inducing apoptosis.

BACKGROUND: Astragaloside III (AS III), a saponin-like metabolite derived from the traditional Chinese medicine Astragali Radix, has been shown to be effective in the treatment of cancer and heart failure, and a variety of digestive disorders. However, its molecular mechanism in the treatment of non-small cell lung cancer (NSCLC) is unknown. METHODS: Human lung cancer A549 cells and NCI-H460 cells and a normal human lung epithelial cell BEAS-2B were treated with different concentrations of AS III. CCK-8 and EdU staining were used to determine the anti-proliferative effects of AS III in vitro. Quantitative proteomic analysis was performed on A549 cells treated with the indicated concentrations of AS III, and the expression levels of apoptosis-related proteins were examined by Western blotting. RESULTS: AS III treatment significantly inhibited proliferation and increased apoptosis in A549 and H460 cells and modulated functional signaling pathways associated with apoptosis and metabolism. At the molecular level, AS III promoted a reduction in the expression of ANXA1 (p < 0.01), with increased levels of cleaved Caspase 3 and PARP 1. In addition, AS III treatment significantly decreased the LC3-I/LC3-II ratio. The results of experiment in vitro showed that AS III promoted NSCLC apoptosis by down-regulating the phosphorylation levels of P38, JNK, and AKT (p < 0.01), inhibiting the expression of Bcl-2 (p < 0.01), and up-regulating the expression of Bax (p < 0.01). CONCLUSION: These findings provide a mechanism whereby AS III treatment induces apoptosis in NSCLC cells, which may be achieved in part via modulation of the P38, ERK and mTOR signaling pathways.

Exploring the Mechanisms of Modified Bu-Shen-Yi-Qi Decoction for COPD-Related Osteoporosis Therapy via Transcriptomics and Network Pharmacology Approach.

Purpose: To investigate the effectiveness of modified Bu-Shen-Yi-Qi decoction (MBSYQ) in the treatment of osteoporosis associated with chronic obstructive pulmonary disease (COPD) and its underlying mechanisms of action. Methods: Disease targets, active ingredients and targets were predicted by TTD, CTD, DisGeNET, HERB (BenCaoZuJian as its Chinese name), and multiple-TCM databases; In addition, the screened targets were performed via the online platforms DAVID 6.8 and Metascape for GO and KEGG pathway enrichment analysis; The relationship between the MBSYQ and core targets were verified by molecular docking technique. Then we established a COPD-associated osteoporosis rat model by passive 24-week cigarette exposure. We assessed the efficacy of MBSYQ by lung histopathology assessment and distal femur/the first lumbar vertebra (L1) microstructural assay. In addition, we performed tibial RNA sequencing, which was validated by RT-PCR and Western blot. Results: Screening revealed that the 350 active compounds of MBSYQ anchored 228 therapeutic targets for COPD-related osteoporosis; KEGG pathway enrichment analysis showed that the key targets mainly regulated MAPK and PI3K/AKT signaling pathways. In vivo studies showed that MBSYQ treatment alleviated pathological alterations in lung tissue, and reversed the bone loss and microstructure damage in the femur/L1 of model rats. The RNA seq indicated that MBSYQ could upregulate genes associated with anti-oxidative stress and aerobic respiration. The GSEA analysis displayed that MAPK and PI3K/AKT pathways were inhibited by CS exposure and activated by MBSYQ. Conclusion: MBSYQ is effective in the prevention and treatment of COPD-related osteoporosis, partially achieved by improving oxygen metabolism and activating MAPK and PI3K/AKT pathways.

[Distribution of bioactive compounds in different tissues of Paeonia lactiflora roots by DESI-MSI and UPLC].

The quality of Paeoniae Radix Alba and Paeoniae Radix Rubra is evaluated by root thickness, and paeoniflorin serves as a common quality indicator of them. However, the correlation between the content of bioactive compounds and the root size is still unclear. Therefore, this study characterized the distribution patterns and content of seven bioactive compounds including paeoniflorin in different tissues of Paeonia lactiflora roots, analyzed the correlation between the root size and the content of bioactive compounds based on the xylem-to-bark ratio, and further determined the index components for quality assessment. Nine samples of fresh P. lactiflora roots were collected from the genuine cultivation area. The distribution of bioactive compounds in different tissues on the cross-section of the root was firstly analyzed by desorption electrospray ionization-mass spectrometry imaging(DESI-MSI). Subsequently, the content of bioactive compounds was determined in the xylems and barks of the roots by UPLC. The compounds with the largest difference between the xylem and the bark were selected by orthogonal partial least squares discriminant analysis(OPLS-DA). The results indicated that paeoniflorin, benzoylpaeoniflorin, oxypaeoniflorin, gallic acid, and 1,2,3,4,6-pentagalloylglucose were significantly accumulated in the xylems, while albiflorin and catechin were mainly distributed in the barks. Paeoniflorin and albiflorin, with the largest differences in the xylem and the bark, had the highest content in the two tissues. The root diameter was positively correlated with paeoniflorin content and negatively correlated with albiflorin content. As isomers with different efficacies, paeoniflorin or albiflorin can be chosen as the quality marker corresponding to specific clinical application to launch quality classification evaluation of multi-functional Chinese medicines.

Exploring the comorbidity mechanisms between asthma and idiopathic pulmonary fibrosis and the pharmacological mechanisms of Bu-Shen-Yi-Qi decoction therapy via network pharmacology.

BACKGROUNDS: Asthma and idiopathic pulmonary fibrosis (IPF) are common chronic diseases of the respiratory system in clinical practice. However, the relationship and molecular links remain unclear, and the current treatment's efficacy is disappointing. Bu-Shen-Yi-Qi (BSYQ) decoction has proven effective in treating various chronic airway inflammatory diseases, including asthma and IPF. But the underlying pharmacological mechanisms are still to be elucidated. METHODS: This study searched the proteins related to asthma and IPF via TTD, CTD, and DisGeNET databases and then submitted to the STRING to establish the protein-protein interaction (PPI) network. The co-bioinformatics analysis was conducted by Metascape. The active ingredients of BSYQ decoction were screened from TCMSP, ETCM, BATMAN-TCM databases, and HPLC/MS experiment. The corresponding targets were predicted based on TCMSP, ETCM, and BATMAN-TCM databases. The shared targets for asthma and IPF treatment were recognized, and further GO and KEGG analyses were conducted with the DAVID platform. Finally, molecule docking via Autodock Vina was employed to predict the potential binding mode between core potential compounds and targets. RESULTS: Finally, 1333 asthma-related targets and 404 IPF-related proteins were retrieved, 120 were overlapped between them, and many of the asthma-related proteins fall into the same statistically significant GO terms with IPF. Moreover, 116 active ingredients of BSYQ decoction were acquired, and 1535 corresponding targets were retrieved. Eighty-three potential compounds and 56 potential targets were recognized for both asthma and IPF treatment. GO and KEGG analysis indicated that the inflammation response, cytokine production, leukocyte differentiation, oxygen level response, etc., were the common pathological processes in asthma and IPF, which were regulated by BSYQ decoction. Molecule docking further predicted the potential binding modes between the core potential compounds and targets. CONCLUSION: The current study successfully clarified the complex molecule links between asthma and IPF and found the potential common targets. Then we demonstrated the efficacy of BSYQ decoction for asthma and IPF treatment from the angle of network pharmacology, which may provide valuable references for further studies and clinical use.

[Di'ao Xinxuekang alleviates non-alcoholic steatohepatitis in mice by up-regulating Nrf2/HO-1 signaling pathway].

The present study investigated the therapeutic effect and mechanism of Di'ao Xinxuekang(DXXK) on non-alcoholic steatohepatitis(NASH) in mice. Sixty-five C57 BL/6 J mice were randomly divided into a normal group and an experimental group for model induction with the high-fat diet for 16 weeks. Then the mice in the experimental group were randomly divided into a model group, an atorvastatin group(4 mg·kg~(-1)·d~(-1)), and high-(200 mg·kg~(-1)·d~(-1)), medium-(60 mg·kg~(-1)·d~(-1)), and low-dose(20 mg·kg~(-1)·d~(-1)) DXXK groups, with 10 mice in each group. Drugs were administered by gavage for eight weeks. Serum lipid, liver lipid, serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione reductase(GSH-Px) were determined. Interleukin-1ß(IL-1ß) and tumor necrosis factor-α(TNF-α) were measured by enzyme-linked immunosorbent assay(ELISA). The liver index was calculated. The liver pathological change and lipid accumulation were observed by HE and oil red O staining. The liver ultrastructure was observed by the transmission electron microscope. The mRNA and protein expression of nuclear factor-erythroid 2 related factor 2(Nrf2) and heme oxygenase-1(HO-1) was detected by real-time fluorescence-based quantitative PCR and Western blot, respectively. The results showed that compared with the normal group, the model group displayed serum lipid and liver lipid metabolism disorders, elevated transaminase, lipid deposition, steatosis, and inflammation, suggesting that the NASH model in mice was properly induced. Compared with the model group, the DXXK groups showed decreased serum lipid, liver lipid, ALT, AST, MDA, IL-1ß, and TNF-α, increased SOD and GSH-Px, alleviated hepatic steatosis, ballooning, and inflammation, and up-regulated Nrf2 and HO-1 gene and protein expression. In conclusion, DXXK can significantly alleviate NASH in mice, which is related to the inhibition of oxidative stress and inflammatory damage by up-regulating the Nrf2/HO-1 signaling pathway.

Efficacy and safety of Tengfu Jiangya tablet combined with valsartan/amlodipine in the treatment of stage 2 hypertension: study protocol for a randomized controlled trial.

BACKGROUND: The prevalence rate of hypertension in the Chinese population is on the rise, and the control rate of hypertension is low. International guidelines, including the 2018 Chinese Guidelines for the Management of Hypertension, recommend optimized drug selection and combination therapy for patients with stage 2 hypertension and blood pressure ≥ 160/100 mmHg, including valsartan/amlodipine (Val/Aml). The traditional Chinese medicine (TCM) compound Tengfu Jiangya tablet (TJT; No. Z20110021, Shandong Provincial Food and Drug Administration) is prepared in the medical institution of Affiliated Hospital of Shandong University of Traditional Chinese Medicine. It is an effective compound preparation of TCM for the treatment of hypertension in the national clinical research base of TCM. The aim of this study was to evaluate the efficacy and safety of TJT combined with Val/Aml in the treatment of stage 2 hypertension with hyperactivity of liver yang. METHODS: This randomized double-blind, placebo-controlled, multicenter trial will be conducted with a total of 288 participants with stage 2 hypertension at seven clinical trial centers. The stratified random method will be used, and the subcenter will be taken as the stratification factor. Eligible patients will be randomly assigned (1:1) into groups receiving either TJT or placebo three times daily for 28 days, both combined with Val/Aml 80/5 mg. The primary efficacy endpoint is the reduction in the mean sitting systolic blood pressure (msSBP) and the mean sitting diastolic blood pressure (msDBP) from baseline to week 4. Adverse events and laboratory test results will be monitored throughout the trial. DISCUSSION: This is the first placebo-controlled randomized trial conducted to evaluate the efficacy and safety of a Chinese herbal extract combined with Val/Aml in patients with stage 2 hypertension. Our study may help to provide evidence-based recommendations of a complementary preventive measure for stage 2 hypertension. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000030611 . Registered on 8 March 2020.

Yi-Zhi-Fang-Dai Formula Exerts a Protective Effect on the Injury of Tight Junction Scaffold Proteins in Vitro and in Vivo by Mediating Autophagy through Regulation of the RAGE/CaMKKß/AMPK/mTOR Pathway.

Alzheimer's disease (AD) is a chronic neurodegeneration disease that is closely related to the abnormal tight junction scaffold proteins (TJ) proteins of the blood-brain barrier (BBB). Recently, Yi-Zhi-Fang-Dai Formula (YZFDF) had exerted a neuronal protective effect against amyloid peptide (Aß) toxicity. Still, the therapeutic mechanism of YZFDF in restoring Aß-induced injury of TJ proteins (ZO-1, Occludin, and Claudin-5) remains unclear. This study aimed to explore the underlying mechanism of YZFDF in alleviating the injury of TJ proteins. We examined the impacts of YZFDF on autophagy-related proteins and the histopathology of Aß in the APP/PS1 double-transgenic male mice. We then performed the free intracellular calcium levels [Ca2+]i analysis and the cognitive behavior test of the AD model. Our results showed that YZFDF ameliorated the injury of TJ proteins by reducing the mRNA transcription and expression of the receptor for advanced glycation end-products (RAGE), the levels of [Ca2+]i, calmodulin-dependent protein kinase ß (CaMKKß), phosphorylated AMP-activated protein kinase (AMPK). Accordingly, YZFDF increased the expression of the phosphorylated mammalian targets of rapamycin (mTOR), leading to inhibition of autophagy (downregulated LC3 and upregulated P62). Moreover, the Aß1-42 oligomers-induced alterations of autophagy in murine mouse brain capillary (bEnd.3) cells were blocked by RAGE small interfering RNA (siRNA). These results suggest that YZFDF restored TJ proteins' injury by suppressing autophagy via RAGE signaling. Furthermore, YZFDF reduced the pathological precipitation of Aß in the hippocampus, and improved cognitive behavior impairment of the AD model suggested that YZFDF might be a potential therapeutic candidate for treating AD through RAGE/CaMKKß/AMPK/mTOR-regulated autophagy pathway.

[Assay of 18 amino acids in Chuanmingshen violaceum roots by pre-column derivative HPLC].

The roots of Chuanmingshen violaceum is a commonly used Chinese herb and food, which contains rich amino acids. However, the kinds and amounts of amino acids are variety in this herb among the geographical location and ecological environment. Therefore, this study firstly developed a new pre-column derived HPLC method to quantify the levels of 18 amino acids in Ch. violaceum roots. Then 24 Ch. violaceum samples were harvested from its main cultivating areas in Sichuan, China. These samples were divided into 4 producing areas based on their geographical sites. The 18 kinds of amino acids were quantified in these sample by the developed method. The differences of these amino acids were further analyzed among these herbal samples and the 4 producing areas by t-test and principal component analysis(PCA). The result indicated the peaks of the 18 kinds of amino acids were separated well in 70 min.The correlation coefficients between peak areas and concentration of these amino acids were more than 0.999 1(n=6). All of their recoveries were in the range of 97.38%-101.3%(n=6).Their detection limit was in the range of 0.003-0.379 µg·mL~(-1).It demonstrates that the developed HPLC method can accurately quantify the amounts of multi-amino acids in this herb. The results of t-test analysis showed the contents of histidine, cystine, leucine, valine, tryptophan, phenylalanine and threonine were significantly different(P<0.05) among the 4 producing areas. But the differences of other amino acids were not significant.The first five factors were extracted by PCA to calculate the comprehensive score. The order of comprehensive score for the 4 producing areas was B(0.603, n=10), C(0.206, n=3), A(-0.283, n=7) and D(-1.167, n=4). The total content of amino acids in Ch. violaceum collected in B producing area was largest(12.5 mg·g~(-1)). It is concluded the Ch. violaceum contains multi-kinds of amino acids. On the basis of amino acid amount, Langzhong city and Cangxi county in Sichuan province(producing area B) is the suitable areas for cultivating Ch. violaceum.

[Kinetic parameters and temperature sensitivity of soil nitrogen and phosphorus transforming enzymes in Robinia pseudoacacia plantations under different vegetation zones on the Loess Plateau, China]. / é»„åœŸé«˜åŽŸä¸åŒæ¤è¢«å¸¦äººå·¥åˆºæ§æž—åœŸå£¤æ°®ç£·è½¬åŒ–é ¶åŠ¨åŠ›å­¦å‚æ•°åŠå ¶æ¸©åº¦æ•æ„Ÿæ€§.

Soil enzymes are catalysts for organic matter decomposition, the kinetic characteristics of which are important indicators of the catalytic performance of enzymes, with important role in evalua-ting soil health quality. We examined the responses of soil enzyme kinetic parameters to temperature change and the variation characteristics of their temperature sensitivity (Q10) in Robinia pseu-doacacia plantation soil under three different vegetation zones on the Loess Plateau. The results showed that the potential maximum reaction rate (Vmax) and the half-saturation constant (Km) of alanine transaminase (ALT), leucine aminopeptidase (LAP) and alkaline phosphatase (ALP) all increased linearly with the increasing incubation temperature. The zonal regularity of forest zone > forest-steppe zone > steppe zone was presented in Vmax. The temperature sensitivity of Vmax(Q10(Vmax)) ranged from 1.14 to 1.62, and the temperature sensitivity of Km(Q10(Km)) ranged from 1.05 to 1.47, with both values being lower in forest-steppe zone than other vegetation zones. In low and high temperature regions, the variations of Q10 in different soil enzymes differed among vegetation zones. Results from redundancy analysis showed that Q10 had a significant correlation with environmental variables, especially soil nutrients, indicating that Q10 would be affected by other environmental factors besides temperature.

Effect of low-level laser therapy on tooth-related pain and somatosensory function evoked by orthodontic treatment.

Low-level laser therapy (LLLT) may have an effect on the pain associated with orthodontic treatment. The aim of this study was to evaluate the effect of LLLT on pain and somatosensory sensitization induced by orthodontic treatment. Forty individuals (12-33 years old; mean ± standard deviations: 20.8 ± 5.9 years) scheduled to receive orthodontic treatment were randomly divided into a laser group (LG) or a placebo group (PG) (1:1). The LG received LLLT (810-nm gallium-aluminium-arsenic diode laser in continuous mode with the power set at 400 mW, 2 J·cm-2) at 0 h, 2 h, 24 h, 4 d, and 7 d after treatment, and the PG received inactive treatment at the same time points. In both groups, the non-treated side served as a control. A numerical rating scale (NRS) of pain, pressure pain thresholds (PPTs), cold detection thresholds (CDTs), warmth detection thresholds (WDTs), cold pain thresholds (CPTs), and heat pain thresholds (HPTs) were tested on both sides at the gingiva and canine tooth and on the hand. The data were analysed by a repeated measures analysis of variance (ANOVA). The NRS pain scores were significantly lower in the LG group (P = 0.01). The CDTs, CPTs, WDTs, HPTs, and PPTs at the gingiva and the PPTs at the canine tooth were significantly less sensitive on the treatment side of the LG compared with that of the PG (P < 0.033). The parameters tested also showed significantly less sensitivity on the non-treatment side of the LG compared to that of the PG (P < 0.043). There were no differences between the groups for any quantitative sensory testing (QST) measures of the hand. The application of LLLT appears to reduce the pain and sensitivity of the tooth and gingiva associated with orthodontic treatment and may have contralateral effects within the trigeminal system but no generalized QST effects. Thus, the present study indicated a significant analgesia effect of LLLT application during orthodontic treatment. Further clinical applications are suggested.

Screening and Analysis of the Marker Components in Ganoderma lucidum by HPLC and HPLC-MSn with the Aid of Chemometrics.

Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, which is a popularly used traditional Chinese medicine for complementary cancer therapy. The present study was to establish a fingerprint evaluation system based on Similarity Analysis (SA), Cluster Analysis (CA) and Principal Component Analysis (PCA) for the identification and quality control of G. lucidum. Fifteen samples from the Chinese provinces of Hainan, Neimeng, Shangdong, Jilin, Anhui, Henan, Yunnan, Guangxi and Fujian were analyzed by HPLC-PAD and HPLC-MSn. Forty-seven compounds were detected by HPLC, of which forty-two compounds were tentatively identified by comparing their retention times and mass spectrometry data with that of reference compounds and reviewing the literature. Ganoderic acid B, 3,7,15-trihydroxy-11,23-dioxolanost-8,16-dien-26-oic acid, lucidenic acid A, ganoderic acid G, and 3,7-oxo-12-acetylganoderic acid DM were deemed to be the marker compounds to distinguish the samples with different quality according to both CA and PCA. This study provides helpful chemical information for further research on the anti-tumor activity and mechanism of action of G. lucidum. The results proved that fingerprints combined with chemometrics are a simple, rapid and effective method for the quality control of G. lucidum.

Effects of short-term weathering on the stable carbon isotope compositions of crude oils and fuel oils.

A short-term simulated weathering experiment was performed on two crude oils and two heavy fuel oils under natural conditions to evaluate the effects of natural weathering processes by using gas chromatography-mass spectrometry combined with gas chromatography-isotopic ratio mass spectrometry. The results of diagnostic ratios of n-alkanes show that only odd to even predominance (OEP1, OPE2) and carbon preference index (CPI) remain stabilized during the 28 d weathering process, but they cannot effectively distinguish the four types of oils. Statistical analyses based on paired sample t-test and principal component analysis (PCA) revealed that stable carbon isotope compositions of n-alkanes in the four studied oils have no significant changes over the weathering time, and that the carbon isotope discrimination (Δδ13C) of n-alkanes is <3‰. We have provided evidence that the stable carbon isotope compositions of n-alkanes compared to n-alkanes diagnostic ratios significantly improve the efficiency and fidelity of the oil fingerprint identification.

Quality Evaluation and Chemical Markers Screening of Salvia miltiorrhiza Bge. (Danshen) Based on HPLC Fingerprints and HPLC-MSn Coupled with Chemometrics.

Danshen, the dried root of Salvia miltiorrhiza Bge., is a widely used commercially available herbal drug, and unstable quality of different samples is a current issue. This study focused on a comprehensive and systematic method combining fingerprints and chemical identification with chemometrics for discrimination and quality assessment of Danshen samples. Twenty-five samples were analyzed by HPLC-PAD and HPLC-MSn. Forty-nine components were identified and characteristic fragmentation regularities were summarized for further interpretation of bioactive components. Chemometric analysis was employed to differentiate samples and clarify the quality differences of Danshen including hierarchical cluster analysis, principal component analysis, and partial least squares discriminant analysis. Consistent results were that the samples were divided into three categories which reflected the difference in quality of Danshen samples. By analyzing the reasons for sample classification, it was revealed that the processing method had a more obvious impact on sample classification than the geographical origin, it induced the different content of bioactive compounds and finally lead to different qualities. Cryptotanshinone, trijuganone B, and 15,16-dihydrotanshinone I were screened out as markers to distinguish samples by different processing methods. The developed strategy could provide a reference for evaluation and discrimination of other traditional herbal medicines.

Yi-Zhi-Fang-Dai Formula Protects against Aß1-42 Oligomer Induced Cell Damage via Increasing Hsp70 and Grp78 Expression in SH-SY5Y Cells.

Yi-Zhi-Fang-Dai formula (YZFDF) is an experiential prescription used to cure dementia cases like Alzheimer's disease (AD). In this study, the main effective compounds of YZFDF have been identified from this formula, and the neuroprotective effect against Aß1-42 oligomer of YZFDF has been tested in SH-SY5Y cells. Our results showed that YZFDF could increase cell viability and could attenuate endothelial reticula- (ER-) mediated apoptosis. Evidence indicated that protein folding and endothelial reticula stress (ERS) played an important role in the AD pathological mechanism. We further explored the expression of Hsp70, an important molecular chaperon facilitating the folding of other proteins, and Grp78, the marker protein of ERS in SH-SY5Y cells. Data told us that YZFDF pretreatment could influence the mRNA and protein expression of these two proteins. At last, we also found that YZFDF pretreatment could activate Akt in SH-SY5Y cells. All these above indicate that YZFDF could be a potent therapeutic candidate for AD treatment.

Transport of Corilagin, Gallic Acid, and Ellagic Acid from Fructus Phyllanthi Tannin Fraction in Caco-2 Cell Monolayers.

Objective. To investigate the absorption property of the representative hydrolyzable tannin, namely corilagin, and its hydrolysates gallic acid (GA) and ellagic acid (EA) from the Fructus Phyllanthi tannin fraction (PTF) in vitro. Methods. Caco-2 cells monolayer model was established. Influences of PTF on Caco-2 cells viability were detected with MTT assay. The transport across monolayers was examined for different time points, concentrations, and secretory directions. The inhibitors of P-glycoprotein (P-gp), multidrug resistance proteins (MRPs), organic anion transporting polypeptide (OATP) and sodium/glucose cotransporter 1 (SGLT1), and tight junction modulators were used to study the transport mechanism. LC-MS method was employed to quantify the absorption concentration. Results. The apparent permeability coefficient (Papp) values of the three compounds were below 1.0 × 10-6 cm/s. The absorption of corilagin and GA were much lower than their efflux, and the uptake of both compounds was increased in the presence of inhibitors of P-gp and MRPs. The absorption of EA was decreased in the company of OATP and SGLT1 inhibitors. Moreover, the transport of corilagin, GA, and EA was enhanced by tight junction modulators. Conclusion. These observations indicated that the three compounds in PTF were transported via passive diffusion combined with protein mediated transport. P-gp and MRPs might get involved in the transport of corilagin and GA. The absorption of EA could be attributed to OATP and SGLT1 protein.

The Genus Phyllanthus: An Ethnopharmacological, Phytochemical, and Pharmacological Review.

The plants of the genus Phyllanthus (Euphorbiaceae) have been used as traditional medicinal materials for a long time in China, India, Brazil, and the Southeast Asian countries. They can be used for the treatment of digestive disease, jaundice, and renal calculus. This review discusses the ethnopharmacological, phytochemical, and pharmacological studies of Phyllanthus over the past few decades. More than 510 compounds have been isolated, the majority of which are lignins, triterpenoids, flavonoids, and tannins. The researches of their remarkable antiviral, antioxidant, antidiabetic, and anticancer activities have become hot topics. More pharmacological screenings and phytochemical investigations are required to support the traditional uses and develop leading compounds.

Structure Identification and Anti-Cancer Pharmacological Prediction of Triterpenes from Ganoderma lucidum.

Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, which is a popularly used traditional Chinese medicine for complementary cancer therapy. In the present study, systematic isolation, and in silico pharmacological prediction are implemented to discover potential anti-cancer active GTs from G. lucidum. Nineteen GTs, three steroids, one cerebroside, and one thymidine were isolated from G. lucidum. Six GTs were first isolated from the fruiting bodies of G. lucidum, including 3ß,7ß,15ß-trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid methyl ester (1), 3ß,7ß,15ß-trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid (2), 3ß,7ß,15α,28-tetrahydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid (3), ganotropic acid (4), 26-nor-11,23-dioxo-5α-lanost-8-en-3ß,7ß,15α,25-tetrol (5) and (3ß,7α)-dihydroxy-lanosta-8,24-dien- 11-one (6). (4E,8E)-N-d-2'-hydroxypalmitoyl-l-O-ß-d-glucopyranosyl-9-methyl-4,8-spingodienine (7), and stigmasta-7,22-dien-3ß,5α,6α-triol (8) were first reported from the genus Ganodema. By using reverse pharmacophoric profiling of the six GTs, thirty potential anti-cancer therapeutic targets were identified and utilized to construct their ingredient-target interaction network. Then nineteen high frequency targets of GTs were selected from thirty potential targets to construct a protein interaction network (PIN). In order to cluster the pharmacological activity of GTs, twelve function modules were identified by molecular complex detection (MCODE) and gene ontology (GO) enrichment analysis. The results indicated that anti-cancer effect of GTs might be related to histone acetylation and interphase of mitotic cell cycle by regulating general control non-derepressible 5 (GCN5) and cyclin-dependent kinase-2 (CDK2), respectively. This research mode of extraction, isolation, pharmacological prediction, and PIN analysis might be beneficial to rapidly predict and discover pharmacological activities of novel compounds.

EGb761 improves cognitive function and regulates inflammatory responses in the APP/PS1 mouse.

There is accumulating evidence that the Ginkgo biloba extract EGb761 may help to prevent Alzheimer's disease (AD). However, the underlying mechanism of its action remains to be elaborated. In this study, we examined the effects of EGb761 using the APP/PS1 transgenic mouse model of AD. Two-month-old APP/PS1 mice were supplemented with EGb761 daily for 6months. We found that this chronic treatment with EGb761 improved the cognitive function of these mice and also significantly alleviated amyloid plaque deposition. Although the level of insoluble amyloid beta (Aß) was decreased, the soluble content of Aß was not changed after administration of EGb761. We then determined the changes in central inflammation and observed that the activated microglia around amyloid plaque was increased in these treated mice. We also found that chronic EGb761 treatment downregulated pro-inflammatory cytokines and inducible nitric oxide synthase (iNOS), and upregulated anti-inflammatory cytokines and Arginase-1 (Arg-1), suggesting that EGb761 regulated the phenotype of activated microglia in the APP/PS1 mouse brain. In support of this, pretreatment of the BV2 microglial cell line with EGb761 inhibited the inflammatory reaction to Aß. Furthermore, the addition of conditioned media derived from BV2 cells that were co-treated with Aß and EGb761, protected neurons against treatment of Aß and inhibited apoptotic damage. Taken together, our results demonstrated that EGb761 provided a protective effect in APP/PS1 mouse. This protection was correlated with an inhibition of the pro-inflammatory effects of microglia and an induction of anti-inflammatory effects. These results strongly suggest that EGb761 provides a protective effect in APP/PS1 mouse via regulation of inflammation in the brain.