Analysis of bioactive components and synergistic action mechanism of ShuGan-QieZhi Capsule for treating non-alcoholic fatty liver disease.

BACKGROUND: ShuGan-QieZhi capsule (SGQZC) is a traditional Chinese preparation used to treat hyperlipidemia and obesity, even non-alcoholic fatty liver disease (NAFLD). However, its therapeutic effects, main bioactive ingredients, as well as potential mechanisms for NAFLD are still unclear. PURPOSE: To investigate the pharmacological effect, main active ingredients, and mechanisms of SGQZC against high-fat diet (HFD)-induced NAFLD in mice. METHODS: NAFLD models were established by feeding C57BL/6 J mice an HFD for 24 weeks. From the 12th week, HFD-fed mice received daily gavage of either SGQZC or silibinin for 12 weeks. Hepatic hypertrophy parameters, along with hepatic and systemic lipid metabolism changes in NAFLD mice, were assessed. Oil red O and histopathological staining techniques determined lipid accumulation and liver injury severity. qRT-PCR analysis measured the expression of genes tied to liver lipid metabolism and inflammation. HPLC-MS/MS identified the primary components of SGQZC in the serum. Human normal hepatocytes (LO2) and hepatic stellate cells (LX-2) were used to screen SGQZC's bioactive ingredients. Network pharmacological analysis, transcriptomics, and western blotting delved into SGQZC's synergistic mechanisms against NAFLD. RESULTS: SGQZC ameliorated abnormal lipid metabolism and liver hypertrophy in mice with HFD-induced NAFLD, consequently reducing hepatic lipid accumulation, inflammatory cell infiltration, and liver impairment. Eight crucial components of SGQZC were detected in serum using HPLC-MS/MS and were found to effectively attenuate lipid accumulation and inflammation in liver cells. Further investigation indicated that SGQZC modulates MAPK pathway and AKT/NF-κB pathway, subsequently improving lipid metabolism and inflammation. CONCLUSION: SGQZC alleviates NAFLD by synergistically modulating the MAPK-mediated lipid metabolism and inhibiting AKT/NF-κB pathways-mediated inflammation. Our findings reveal the enormous potential of SGQZC for the treatment of NAFLD, providing a possible new clinical therapeutic strategy.

Orchestrated Cytosolic Delivery of Antigen and Adjuvant by Manganese Ion-Coordinated Nanovaccine for Enhanced Cancer Immunotherapy.

Cancer vaccines have received tremendous attention in cancer immunotherapy due to their capability to induce a tumor-specific immune response. However, their effectiveness is compromised by the insufficient spatiotemporal delivery of antigens and adjuvants in the subcellular level to induce a robust CD8+ T cell response. Herein, a cancer nanovaccine G5-pBA/OVA@Mn is prepared through multiple interactions of manganese ions (Mn2+), benzoic acid (BA)-modified fifth generation polyamidoamine (G5-PAMAM) dendrimer, and the model protein antigen ovalbumin (OVA). In the nanovaccine, Mn2+ not only exerts a structural function to assist OVA loading as well as its endosomal escape, but works as an adjuvant of stimulator of interferon genes (STING) pathway. These collaboratively facilitate the orchestrated codelivery of OVA antigen and Mn2+ into cell cytoplasm. Vaccination with G5-pBA/OVA@Mn not only shows a prophylactic effect, but also significantly inhibits growth against B16-OVA tumors, indicating its great potential for cancer immunotherapy.

Observation of complications assessed by Clavien-Dindo classification in different endoscopic procedures of benign prostatic hyperplasia: An observational study.

The Clavien-Dindo classification (CDC) was widely used in the assessment of surgical complications, but some inconsistencies always existed in urological literature. This study was aimed to report complications of the transurethral resection of the prostate (TURP), plasmakinetic resection of the prostate (PKRP), and holmium laser enucleation of the prostate (HoLEP) by using a more detailed way under the framework of CDC. A total of 623 eligible cases underwent endoscopic procedures from January 2018 and December 2020 were divided into the TURP group (212 cases), the PKRP group (208 cases), and the HoLEP group (203 cases) according to the surgical type. Patients' surgical complications assessed by the CDC were compared among the 3 groups. The operation time, intraoperative irrigation volume, postoperative irrigation time and volume, decrease in hemoglobin and sodium, postoperative catheterization time, visual analogue scale, hospital stay of the PKEP group and the HoLEP group were significantly less than those of the TURP group, and the decrease in hemoglobin and visual analogue scale in the HoLEP group were significantly lower than those in the PKEP group (all P < .05). The electrolyte disturbance, urinary tract irritation, and patients with grade II of CDC in the PKRP group were significantly lower than those in the TURP group; The electrolyte disturbance, lower abdominal pain, urinary tract irritation, intraoperative hemorrhage, secondary hemorrhage, clot retention, patients with grade I, II, III of CDC in the HoLEP group were significantly lower than those in the TURP group, and the urinary tract irritation, grade I, II of CDC in the HoLEP group was significantly lower than that in the PKRP group (all P < .05). The CDC should be recommended because of the enhanced insight into surgical complications, and the HoLEP should be given a priority for Benign prostatic hyperplasia (BPH) surgical treatment in terms of the merits in surgical characteristics and complications.

[Simultaneous determination and pharmacokinetic study of five compounds from total extract of Clinopodium chinense in abnormal uterine bleeding rat plasma by UPLC-MS/MS].

Clinopodium chinense, a traditional folk medicinal herb, has been used to treat abnormal uterine bleeding(AUB) for many years. Saponins and flavonoids are the main active components in C. chinense. To study the pharmacokine-tics of multiple components from the total extract of C. chinense(TEC), we established a sensitive and rapid method of ultra-perfor-mance liquid chromatography coupled with tandem mass spectrometry(UPLC-MS/MS) for simultaneous determination of five compounds in the plasma of AUB rats. After validation, the AUB model was established with SD female rats which got pregnant on the same day by gavage with mifepristone(12.4 mg·kg~(-1)) and misoprostol(130 µg·kg~(-1)). The established method was applied to the detection of hesperidin, naringenin, apigenin, saikosaponin a, and buddlejasaponin Ⅳb in AUB rats after the administration of TEC. The pharmacokinetic parameters were calculated by DAS 2.0. The five compounds showed good linear relationship within the detection range. The specificity, accuracy, precision, recovery, matrix effect, and stability of the method all matched the requirements of biolo-gical sample detection. The above 5 compounds were detected in the plasma of AUB rats after the administration of TEC. The C_(max) va-lues of hesperidin, naringenin, apigenin, saikosaponin a, and clinoposide A were 701.6, 429.5, 860.7, 75.1, and 304.1 ng·mL~(-1), respectively. All the compounds owned short half-life and quick elimination rate in vivo, and the large apparent volume of distribution indicated that they were widely distributed in tissues. Being rapid, accurate, and sensitive, this method is suitable for the pharmacokinetic study of extracts of Chinese herbal medicines and provides a reference for the study of pharmacodynamic material basis of C. chinense in treating AUB.

[Anti-inflammatory and hemostatic effects of total extract, saponins, and flavonoids of Clinopodium chinense in female rats with abnormal uterine bleeding and mechanism].

This study aims to explore the anti-inflammatory and hemostatic effects of the total extract of Clinopodium chinense(TEC), total saponins of C. chinense(TSC), and total flavonoids of C. chinense(TFC) in female rats with abnormal uterine bleeding(AUB), and the possible mechanism. Mifepristone(i.g., 12.4 mg·kg~(-1)) and misoprostol(i.g., 130 µg·kg~(-1)) were used to induce AUB in SD female rats conceiving on the same day. Then the AUB rats were randomized into model group, TEC group, TSC group, TFC group, Yimucao Granules(LG) group, and estradiol valerate(EV) group, with 8 rats in each group. Another 8 non-pregnant female rats were selected as normal group. During the experiment, each group was given the corresponding drug by gavage once a day for 7 days. After the administration, blood and uterine tissue were collected. The uterine bleeding volume was measured by ultraviolet spectrophotometry and the pathological changes of endometrium were observed based on hematoxylin-eosin(HE) staining. In addition, the microvessel density of endometrium was determined by immunohistochemistry, and the content of thromboxane B2(TXB2), 6-keto-PGF_(1α), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in plasma and levels of lutenizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E_2), and progesterone in serum were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA and protein expression of estrogenreceptor α(ERα), progesterone receptor(PR), matrix metalloproteinase(MMP)-2, MMP-9, and vascular endothelial growth factor(VEGF) in uterine tissue was determined by Western blot. Compared with the model group, TEC, TSC, and TFC can reduce uterine bleeding volume, alleviate the pathological damage of endometrium, and increase the microvessel density in endometrium. Moreover, TEC and TSC can significantly raise plasma TXB2 level and ratio of TXB2 to 6-keto-PGF_(1α), and TEC and TFC can significantly reduce the levels of IL-6 and TNF-α. In addition, TEC significantly elevated serum progesterone level and TFC significantly increased serum levels of E_2, FSH, and LH. TSC can significantly raise serum progesterone and FSH levels. In addition, TEC can significantly down-regulate the protein expression of PR, MMP-2, and VEGF and TSC significantly reduced the expression of MMP-9. TFC significantly decreased the expression of PR, MMP-9, and VEGF, and up-regulated the expression of ERα. In conclusion, TEC, TSC, and TFC all show therapeutic effects on AUB, particularly TEC. TSC exerts the effects by enhancing the coagulation function and promoting endometrial repair, and TFC by regulating estrogen levels and reducing inflammatory response. This study reveals the mechanism of C. chinense against AUB and also explains the holistic characteristics of Chinese medicine.

Postoperative hypothalamic damage predicts postoperative weight gain in patients with adult-onset craniopharyngioma.

OBJECTIVE: This study aimed to recapitulate the change trajectory of postoperative weight and investigate the association between postoperative hypothalamic damage and weight gain and hypothalamic obesity (HO) in patients with adult-onset craniopharyngioma. METHODS: The data of 96 patients with surgically treated primary adult-onset craniopharyngioma were retrospectively analyzed. The association between postoperative hypothalamic damage based on magnetic resonance images or endoscopic observation and postoperative weight gain and HO was determined by multivariable logistic regression. RESULTS: Forty-seven (49.0%) patients and 18 (18.8%) patients experienced clinically meaningful weight gain (≥5%) and HO at last follow-up, respectively. Postoperative weight significantly increased during the first 6 months following surgery, followed by stabilization. Both grade 2 postoperative hypothalamus damage, as evaluated by the magnetic resonance imaging classification system of Müller et al., and higher scores based on the Roth et al. hypothalamic lesion score were significantly associated with postoperative weight gain of ≥5% (p = 0.005 and p = 0.002) and with HO (p = 0.001 and p = 0.008). Additionally, bilateral hypothalamic injury as evaluated by the Hong et al. hypothalamic injury pattern based on endoscopic observation (p = 0.008) could predict postoperative weight gain ≥5%. CONCLUSIONS: Significant postoperative weight gain is common in patients with adult-onset craniopharyngioma. Postoperative hypothalamic damage can predict clinically meaningful weight gain and HO.

Exploring the Mechanism of Danshensu in the Treatment of Doxorubicin-Induced Cardiotoxicity Based on Network Pharmacology and Experimental Evaluation.

Background: Doxorubicin (DOX) is one of the most effective chemotherapeutic agents available; however, its use is limited by the risk of serious cardiotoxicity. Danshensu (DSS), an active ingredient in Salvia miltiorrhiza, has multiple cardioprotective effects, but the effect of DSS on DOX-induced cardiotoxicity has not been reported. Objectives: Predicting the targets of DOX-induced cardiotoxicity and validating the protective effects and mechanisms of DSS. Methods: (1) Using methods based on network pharmacology, DOX-induced cardiotoxicity was analyzed by data analysis, target prediction, PPI network construction and GO analysis. (2) The cardiotoxicity model was established by continuous intraperitoneal injection of 15 mg/kg of DOX into mice for 4 days and the protective effects and mechanism were evaluated by treatment with DSS. Results: The network pharmacology results indicate that CAT, SOD, GPX1, IL-6, TNF, BAX, BCL-2, and CASP3 play an important role in this process, and Keap1 is the main target of DOX-induced cardiac oxidative stress. Then, based on the relationship between Keap1 and Nrf2, the Keap1-Nrf2/NQO1 pathway was confirmed by animal experiments. In the animal experiments, by testing the above indicators, we found that DSS effectively reduced oxidative stress, inflammation, and apoptosis in the damaged heart, and significantly alleviated the prolonged QTc interval caused by DOX. Moreover, compared with the DOX group, DSS elevated Keap1 content and inhibited Nrf2, HO-1, and NQO1. Conclusion: The results of network pharmacology studies indicated that Keap1-Nrf2/NQO1 is an important pathway leading to DOX-induced cardiotoxicity, and the results of animal experiments showed that DSS could effectively exert anti-oxidative stress, anti-inflammatory and anti-apoptotic therapeutic effects on DOX-induced cardiotoxicity by regulating the expression of Keap1-Nrf2/NQO1.

Pharmacological mechanism of JiaWeiSiWu granule in the treatment of hypertension based on network pharmacology.

BACKGROUND: JiaWeiSiWu granule (JWSWG) has been applied clinically for more than a decade, and the preliminary results show that blood pressure can be reduced while protecting the target organ at the same time. The purpose of this research is to study the pharmacological mechanism of JWSWG in treating hypertension using network pharmacology. METHODS: The chief active components, relevant targets, and the target genes of JWSWG were retrieved by the databases TCMSP and UniProt. The GeneCards database was used to obtain target genes of hypertension. Then, the target genes of hypertension and active components were intersected to discover the potential targets by which JWSWG acts on hypertension. Cytoscape software was employed to construct the "medicine-compound-target-disease" network. The STRING database was used to construct the protein-protein interaction network in order to screen the key target genes. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed by RGUI and org.Hs.eg.db. RESULTS: By intersecting 102 compound target genes with 6,732 target genes of hypertension, 88 action target genes were obtained, thereby screening out the key compounds and key targets. The results of GO enrichment showed the main molecular functions, biological processes, and cellular components. The main pathways of JWSWG in treating hypertension were revealed by KEGG pathway enrichment. CONCLUSIONS: This research clarified the mechanism of JWSWG in the treatment of hypertension systematically, providing new potential ideas and a theoretical foundation for further experimental and clinical research.

Supplementation with asiatic acid during in vitro maturation improves porcine oocyte developmental competence by regulating oxidative stress.

Asiatic acid is a natural triterpene found in Centella asiatica that acts as an effective free radical scavenger. Our previous research showed that asiatic acid delayed porcine oocyte ageing in vitro and improved preimplantation embryo development competence in vitro; however, the protective effects of asiatic acid against oxidative stress in porcine oocyte maturation are still unclear. Here, we investigated the effects of asiatic acid on porcine oocyte in vitro maturation (IVM) and subsequent embryonic development competence after parthenogenetic activation (PA) and in vitro fertilization (IVF). The results of the present research showed that 10 µM asiatic acid supplementation did not affect the expansion of cumulus cells or polar body extrusion of porcine oocytes, while asiatic acid application significantly increased the subsequent blastocyst formation rate and quality of porcine PA and IVF embryos. Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that induces oxidative stress in porcine oocytes. As expected, asiatic acid supplementation not only decreased intracellular ROS levels but also attenuated H2O2-induced intracellular ROS generation. Further analysis revealed that asiatic acid supplementation enhanced intracellular glutathione production, mitochondrial membrane potential, and ATP generation at the end of IVM. In summary, our results reveal that asiatic acid supplementation exerts beneficial effects on porcine oocytes by regulating oxidative stress during the IVM process and could act as a potential antioxidant in porcine oocytes matured in vitro production systems.

Active-Ingredient Screening and Synergistic Action Mechanism of Shegan Mixture for Anti-Asthma Effects Based on Network Pharmacology in a Mouse Model of Asthma.

BACKGROUND: Shegan Mixture (SGM) is a traditional Chinese medicine that has anti-inflammatory and therapeutic effects on asthma. However, its active ingredients and combined action mechanism have not been fully elucidated so far. The purpose of this study was to screen the effective ingredients and targets and elucidate the synergistic action mechanism of SGM in asthma mice using the network pharmacological approach. METHODS: A mouse model of asthma model was used in this study. Mice were orally administered SGM at three doses for 4 weeks and the effect of SGM on asthma was evaluated. The active ingredients and their targets of SGM were identified by searching databases, such as Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). The main active ingredients were selected with parameters OB and DL. The synergistic action mechanisms of SGM in asthma were studied through key active ingredient-target interaction network and verified using surface plasmon resonance assay (SPR). RESULTS: SGM exerts anti-asthmatic effects by reducing lung tissue damage and inflammatory factors (IFN-γ, IL-4, IL-5, and IL-13) in asthmatic mice. Twenty ingredients and 45 related proteins were selected as potential nodes using enrichment analysis and network analysis. Inflammation and smooth muscle regulation-related pathways were considered to be the main pharmacological mechanisms of SGM in the treatment of asthma. Especially, 5 molecule-target pairs (including 3 ingredients and 4 proteins) were well docked with each other and the SPR assay revealed that glabridin-PTGS2 had good binding with 44.5 µM Kd value. CONCLUSION: SGM exerts the synergistic anti-asthma effects by virtue of reducing lung-tissue damage and inflammatory factors in asthmatic mice, which explains the theoretical basis for the traditional Chinese medicine, SGM, to treat asthma. Our study thus sheds light on a variety of options including Chinese medicine that could potentially be used in the clinical treatment of asthma.

Addressing the role of 11ß-hydroxysteroid dehydrogenase type 1 in the development of polycystic ovary syndrome and the putative therapeutic effects of its selective inhibition in a preclinical model.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common metabolic and endocrine disorder among reproductive-age women, and the leading cause of anovulatory infertility. 11ß-hydroxysteroid dehydrogenases-1 (11ß-HSD1) catalysing the conversion of inactive cortisone to active cortisol plays a crucial role in various metabolic diseases. However, whether 11ß-HSD1 is associated with the pathogenesis of PCOS and whether 11ß-HSD1 can be a treating target of PCOS remain unknown. METHODS: This study was first designed to explore the role of 11ß-HSD1 in PCOS development and the effect of selective 11ß-HSD1 inhibitor administration on PCOS treatment. Follicular fluid and granulosa cells (GCs) were collected from 32 non-PCOS patients and 37 patients with PCOS to measure cortisol and 11ß-HSDs levels. Female Sprague-Dawley rats (3-week-old) were injected with dehydroepiandrosterone (DHEA) to induce PCOS and their ovaries were collected to measure the abundance of corticosterone (CORT) and 11ß-HSDs. To determine the role of 11ß-HSD1 in PCOS development, we overexpressed 11ß-HSD1 in the ovaries of female rats (5-week-old) or knocked down the expression of 11ß-HSD1 in the ovaries from PCOS rats via lentivirus injection. After lentivirus infection, the body weights, ovarian weights, estrous cycles, reproductive hormones and morphology of the ovary were analysed in rats from different experimental groups. Then to figure out the translational potential of the selective 11ß-HSD1 inhibitor in treating PCOS, PCOS rats were treated with BVT.2733, a selective 11ß-HSD1 inhibitor and a cluster of PCOS-like traits were analysed, including insulin sensitivity, ovulatory function and fertility of rats from the Control, PCOS and PCOS+BVT groups. Rat ovarian explants and human GCs were used to explore the effect of CORT or cortisol on ovarian extracellular matrix remodelling. RESULTS: The elevated expression of 11ß-HSD1 contributed to the increased cortisol and corticosterone (CORT) concentrations observed in the ovaries of PCOS patients and PCOS rats respectively. Our results showed that ovarian overexpression of 11ß-HSD1 induced a cluster of PCOS phenotypes in rats including irregular estrous cycles, reproductive hormone dysfunction and polycystic ovaries. While knockdown of ovarian 11ß-HSD1 of PCOS rats reversed these PCOS-like changes. Additionally, the selective 11ß-HSD1 inhibitor BVT.2733 alleviated PCOS symptoms such as insulin resistance (IR), irregular estrous cycles, reproductive hormone dysfunction, polycystic ovaries, ovulatory dysfunction and subfertility. Moreover, we showed that cortisol target ovarian insulin signalling pathway and ovarian extracellular matrix (ECM) remodelling in vivo, in ovarian explants and in GCs. CONCLUSION: Elevated 11ß-HSD1 abundance in ovarian is involved in the pathogenesis of PCOS by impairing insulin signalling pathway and ECM remodelling. Selective inhibition of 11ß-HSD1 ameliorates a cluster of PCOS phenotypes. Our study demonstrates the selective 11ß-HSD1 inhibitor as a novel and promising strategy for the treatment of PCOS.

Dihydrophenanthrenes from medicinal plants of Orchidaceae: A review.

The plants of Orchidaceae are widely distributed in the world, 47 species of which have been used as folk medicines with a long history. The tubers and stems of them exhibit diverse efficacy, including clearing heat and resolving toxin, moistening lung and relieving cough and promoting blood circulation. Since dihydrophenanthrenes were responsible for the medical purposes, the characteristic skeletons, pharmacological effects and clinical applications of dihydrophenanthrenes were summarized in this review, so as to provide a theoretical basis for the comprehensive study, development and application of DPs from medicinal plants of Orchidaceae.

Transcriptome sequencing and metabolome analysis reveal the mechanism of Shuanghua Baihe Tablet in the treatment of oral mucositis / 中国天然药物

Oral mucositis (OM) caused by cancer therapy is the most common adverse reaction in the radiotherapy of head and neck tumors. In severe cases, it can lead to the interruption of treatment, which affects the control of the disease and the quality of life. Shuanghua Baihe Tablet (SBT) is a traditional Chinese medicine (TCM) formula, which is administerd to treat OM in China. It has been clinically effective for more than 30 years, but the underlying mechanism is not completely understood. With the development of multiple omics, it is possible to explore the mechanism of Chinese herbal compound prescriptions. Based on transcriptomics and metabolomics, we explored the underlying mechanism of SBT in the treatment of OM. An OM model of rats was established by 5-FU induction, and SBT was orally administered at dosages of 0.75 and 3 g·kg

A new hexenol glycoside from Buddleja officinalis / 中国中药杂志

The chemical constituents of the flower buds of Buddleja officinalis were investigated in this study. Eight compounds were isolated from the water extract of B. officinalis by column chromatography, and their structures were elucidated on the basis of physicochemical properties and spectral data. These compounds were identified as(Z)-hex-3-en-1-ol-1-O-β-D-glucopyranosyl-(1→2)-[β-D-xylcopyranosyl-(1→6)]-β-D-glucopyranoside(1), ebracteatoside B(2), jasmonic acid-11-O-β-D-glucopyranoside(3), 6-hydroxyluteolin-7-O-β-D-glucopyranoside(4), luteolin-7-O-galacturonide(5), vicenin-2(6), decaffeoylverbascoside(7), and 6-O-(E)-feruloyl-D-glucopyranoside(8). Compound 1 is a new 3-hexenol glycoside. Compounds 2, 3, and 6 were isolated from Buddleja genus for the first time, and compounds 4 and 5 were isolated from this plant for the first time.

Network Pharmacology Strategy to Investigate the Pharmacological Mechanism of HuangQiXiXin Decoction on Cough Variant Asthma and Evidence-Based Medicine Approach Validation.

OBJECTIVE: To investigate the pharmacological mechanism of HuangQiXiXin decoction (HQXXD) on cough variant asthma (CVA) and validate the clinical curative effect. METHODS: The active compounds and target genes of HQXXD were searched using TCMSP. CVA-related target genes were obtained using the GeneCards database. The active target genes of HQXXD were compared with the CVA-related target genes to identify candidate target genes of HQXXD acting on CVA. A medicine-compound-target network was constructed using Cytoscape 3.6.0 software, and a protein-protein interaction (PPI) network was constructed using the STRING database. Gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using RGUI3.6.1 and Cytoscape 3.6.0. We searched the main database for randomized controlled trials of HQXXD for CVA. We assessed the quality of the included studies using the Cochrane Reviewers' Handbook. A meta-analysis of the clinical curative effect of HQXXD for CVA was conducted using the Cochrane Collaboration's RevMan 5.3 software. RESULTS: We screened out 48 active compounds and 217 active target genes of HQXXD from TCMSP. The 217 active target genes of HQXXD were compared with the 1481 CVA-related target genes, and 132 candidate target genes for HQXXD acting on CVA were identified. The medicine-compound-target network and PPI network were constructed, and the key compounds and key targets were selected. GO function enrichment and KEGG pathway enrichment analysis were performed. Meta-analysis showed that the total effective rate of the clinical curative effect was significantly higher in the experimental group than the control group. CONCLUSION: The pharmacological mechanism of HQXXD acting on CVA has been further determined, and the clinical curative effect of HQXXD on CVA is remarkable.

Revealing active components, action targets and molecular mechanism of Gandi capsule for treating diabetic nephropathy based on network pharmacology strategy.

BACKGROUND: Gandi capsule is a traditional Chinese herbal formula used to promote blood circulation and removing blood stasis in clinical. Our previous study has shown that it reduces proteinuria with routine treatment in diabetic nephrophy (DN), but its pharmacological action mechanism is still unknown. METHODS: To facilitate the identification of components, a component database of Gandi capsule and target database of DN were established by ourselves. The components absorbed in blood circle were identified in rat plasma after oral administration of Gandi capsule by UHPLC-QQQ-MS/MS. The potential targets were screened by using Libdock tolls in Discovery studio 3.0. Then Pathway and Network analyses were used to enrich the screened targets. The possible targets were verified by using a surface plasmon resonance (SPR) test and the molecular mechanism focusing these targets for treating DN was clarified by western blot. RESULTS: Six components in Gandi capsule were identified detected in rat plasma after oral administration by UHPLC-QQQ-MS/MS. After molecular docking analyses in KEGG and Discovery studio, four protein targets including HNF4A, HMGCR, JAK3, and SIRT1, were screened out, and proved as effective binding with baicalin, wogonoside by SPR. And the molecular mechanism was clarified that baicalin and wogonoside inhibit the effect of high glucose (HG)-induced decreased cell viability and podocin expression, and strengthen the activation p-AKT, p-PI3K, and p-AMPK. CONCLUSION: Baicalin and wogonoside were screened out to be the active compounds in Gandi capsule and can ameliorate HG-induced podocyte damage by influencing the AMPK and PI3K-AKT signaling pathways by binding with HNF4A, HMGCR, JAK3, and SIRT1.

Efficacy and safety of local infiltration analgesia for pain management in total knee and hip arthroplasty: A meta-analysis of randomized controlled trial.

BACKGROUND: Local infiltration analgesia (LIA) has become popular in postoperative pain relief after total hip arthroplasty (THA) or total knee arthroplasty (TKA). The aim of this meta-analysis was to compare the efficacy and safety of LIA with intrathecal morphine and epidural analgesia after THA and TKA. METHODS: A systematic article search was performed from PubMed, Embase, and Web of Science databases, up to February 21, 2019. The main outcomes included visual analog scale for assessment of pain, morphine equivalent consumption, length of hospital stay, and adverse events. The data were calculated using weight mean difference (WMD) or risk ratio (RR) with 95% confidence intervals (95% CIs). RESULTS: Eleven studies with a total of 707 patients met the inclusion criteria and were included in this meta-analysis. LIA provided better pain control than other 2 techniques at 24-hour (WMD = 10.61, 95% CI: 3.36-17.87; P = .004), 48-hour (WMD = 16.0, 95% CI: 8.87-23.13; P < .001), and 72-hour (WMD = 11.31, 95% CI: 3.78-18.83; P < .001). Moreover, LIA had similar morphine consumption and duration of hospital stay with intrathecal morphine and epidural analgesia. There was significantly lower incidence of adverse events with LIA than with the other 2 techniques. CONCLUSION: LIA provided better postoperative pain control and less adverse events than intrathecal morphine and epidural analgesia after THA and TKA.

Radix Astragali and Radix Angelicae Sinensis in the Treatment of Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-analysis.

INTRODUCTION: There are many clinical studies in the treatment of idiopathic pulmonary fibrosis (IPF) with herbal medicine including Astragalus mongholicus Bunge, Radix Astragali (RA) and Angelica sinensis (Oliv.) Diels, Radix Angelicae Sinensis (RAS). These have obtained good curative effect. There is no systematic evaluation on the clinical efficacy of RA and RAS in patients with IPF. The aim of this systematic review and meta-analysis was to critically evaluate the current evidence of efficacy and safety of RA and RAS in IPF. METHODS: We searched the primary database for randomized controlled trial (RCT) of RA and RAS treating IPF. We assessed the quality of included studies using the Jadad rating scale and referred to the Cochrane Reviewer's Handbook for guidelines to assess the risk of bias. We extracted the main outcomes of included RCTs and a meta-analysis was conducted using the Cochrane Collaboration's RevMan5.3 software. RESULTS: Seventeen eligible RCTs were identified and made a systematic review and meta-analysis. Risk of bias and quality of included RCTs were carried out. The results of meta-analysis showed that total effective rate and traditional Chinese medicine syndrome effective rate were statistically significantly higher in the experimental group than the control group, main pulmonary function index, six minute walking distance and Borg scale questionnaire score were statistically significantly better in the experimental group than the control group and incidence of adverse reactions was statistically significantly lower in the experimental group than the control group. CONCLUSION: RA and RAS are effective and safe in the treatment of IPF, which is beneficial to pulmonary function and exercise tolerance of these patients.

Asiatic acid supplementation during the in vitro culture period improves early embryonic development of porcine embryos produced by parthenogenetic activation, somatic cell nuclear transfer and in vitro fertilization.

Asiatic acid is a pentacyclic triterpene enriched in the medicinal herb Centella asiatica, and it has been suggested to possess free radical scavenging and anti-apoptotic properties. The purpose of the current study was to explore the effects of asiatic acid on porcine early-stage embryonic development and the potential mechanisms for any observed effects. The results showed that 10 µM asiatic acid supplementation during the in vitro culture period dramatically improved developmental competence in porcine embryos derived from parthenogenetic activation (PA), somatic cell nuclear transfer (SCNT) and in vitro fertilization (IVF). Further analysis revealed that asiatic acid attenuated H2O2-induced intracellular reactive oxygen species (ROS) generation. Notably, asiatic acid not only enhanced intracellular GSH levels but also attenuated mitochondrial dysfunction. Gene expression analysis revealed that asiatic acid upregulated expression of the antioxidant-related gene Sod-1 and the blastocyst formation related gene Cox-2, while downregulating expression of the apoptosis-related gene Caspase-9 in SCNT blastocysts. These results suggest that asiatic acid exerts beneficial effects on early embryonic development in porcine embryos and that asiatic acid may be useful for improving the in vitro production of porcine embryos.

Elucidation of the Intestinal Absorption Mechanism of Loganin in the Human Intestinal Caco-2 Cell Model.

Loganin, iridoid glycosides, is the main bioactive ingredients in the plant Strychnos nux-vomica L. and demonstrates various pharmacological effects, though poor oral bioavailability in rats. In this study, the intestinal absorption mechanism of loganin was investigated using the human intestinal Caco-2 cell monolayer model in both the apical-to-basolateral (A-B) and the basolateral-to-apical (B-A) direction; additionally, transport characteristics were systematically investigated at different concentrations, pHs, temperatures, and potential transporters. The absorption permeability (PappAB) of loganin, which ranged from 12.17 to 14.78 × 10-6cm/s, was high at four tested concentrations (5, 20, 40, and 80µM), while the major permeation mechanism of loganin was found to be passive diffusion with active efflux mediated by multidrug resistance-associated protein (MRP) and breast cancer resistance protein (BCRP). In addition, it was found that loganin was not the substrate of efflux transporter P-glycoprotein (P-gp) since the selective inhibitor (verapamil) of the efflux transporter exhibited little effects on the transport of loganin in the human intestinal Caco-2 cells. Meanwhile, transport from the apical to the basolateral side increased 2.09-fold after addition of a MRP inhibitor and 2.32-fold after addition of a BCRP inhibitor. In summary, our results clearly demonstrate, for the first time, a good permeability of loganin in the human intestinal Caco-2 cell model and elucidate, in detail, the intestinal absorption mechanism and the effects of transporters on iridoid glycosides compounds.