Gypenoside XIII regulates lipid metabolism in HepG2 hepatocytes and ameliorates nonalcoholic steatohepatitis in mice.

Gypenoside XIII is isolated from Gynostemma pentaphyllum (Thunb.) Makino. In mice, G. pentaphyllum extract and gypenoside LXXV have been shown to improve non-alcoholic steatohepatitis (NASH). This study investigated whether gypenoside XIII can regulate lipid accumulation in fatty liver cells or attenuate NASH in mice. We used HepG2 hepatocytes to establish a fatty liver cell model using 0.5 mM oleic acid. Fatty liver cells were treated with different concentrations of gypenoside XIII to evaluate the molecular mechanisms of lipid metabolism. In addition, a methionine/choline-deficient diet induced NASH in C57BL/6 mice, which were given 10 mg/kg gypenoside XIII by intraperitoneal injection. In fatty liver cells, gypenoside XIII effectively suppressed lipid accumulation and lipid peroxidation. Furthermore, gypenoside XIII significantly increased SIRT1 and AMPK phosphorylation to decrease acetyl-CoA carboxylase phosphorylation, reducing fatty acid synthesis activity. Gypenoside XIII also decreased lipogenesis by suppressing sterol regulatory element-binding protein 1c and fatty acid synthase production. Gypenoside XIII also increased lipolysis and fatty acid ß-oxidation by promoting adipose triglyceride lipase and carnitine palmitoyltransferase 1, respectively. In an animal model of NASH, gypenoside XIII effectively decreased the lipid vacuole size and number and reduced liver fibrosis and inflammation. These findings suggest that gypenoside XIII can regulate lipid metabolism in fatty liver cells and improve liver fibrosis in NASH mice. Therefore, gypenoside XIII has potential as a novel agent for the treatment of NASH.

Koumine ameliorates neuroinflammation by regulating microglia polarization via activation of Nrf2/HO-1 pathway.

BACKGROUND: Gelsemium elegans (Gardner & Chapm.) Benth (G. elegans) has been widely used as a traditional folk medicine in China and Southeast Asia. As the most abundant alkaloid in G. elegans, Koumine (KM) has been revealed the effect of inflammatory attenuation modulating by macrophage activation and polarization. PURPOSE: This study aimed to explore the effect of KM on modulation of microglia polarization that led to the suppression of neuroinflammation and further improved neurodegenerative behavior. METHODS: Inflammatory mediators, microglia M1 and M2 phenotype markers and Nrf2/HO-1 pathway related protein were assessed in LPS-induced BV2 cells and LPS-treated mice by RT-PCR, immunohistochemistry, immunofluorescence and Western blotting. Moreover, the learning and memory abilities of mice were evaluated by Morris water maze test, and the neuronal damage was evaluated by the Nissl staining. RESULTS: KM attenuated LPS-induced viability and morphological changes in BV2 microglial cells. Our findings showed that KM activated the Nrf2/HO-1 signaling pathway to promote phenotypic switch from M1 to M2 phenotypes. This switch suppresses the release of inflammatory mediators in LPS-induced BV2 cells. Meanwhile, KM attenuated neuroinflammation through modulating microglia polarization and subsequently reversed the behavioral alterations in LPS-induced mice model of neuroinflammation. CONCLUSIONS: KM may alleviate neuroinflammation by regulating microglia polarization with the involvement of Nrf2/HO-1 pathway, resulting of the neuroprotective effect.

Gastrodia elata BI.:A Comprehensive Review of Its Traditional Use, Botany, Phytochemistry, Pharmacology, and Pharmacokinetics.

Materials and Methods: This article collects information from relevant documents, including scientific papers, books, and dissertations concerning Gastrodia elata BI. Results: To date, research on Gastrodia elata BI. has identified about 100 active compounds. Many compounds in Gastrodia elata BI. have biological activities, such as sedation and hypnosis, anticonvulsion, improvement of learning and memory, protection of neurons, antidepressive effects, lowering of blood pressure, promotion of angiogenesis, protection of cardiomyocytes, antiplatelet aggregation, anti-inflammatory activity, and amelioration of labor pains. Conclusion: Although many traditional uses of this plant have been confirmed, it is necessary to continue to study the relationship between its structure and function, clarify the mechanisms of pharmacological effects, and explore new clinical applications so as to better delineate the quality control standards for Gastrodia elata BI.

Transcutaneous Electrical Acupoints Stimulation Improves Spontaneous Voiding Recovery After Laparoscopic Cholecystectomy: A Randomized Clinical Trial.

BACKGROUND: Facilitating the recurrence of spontaneous voiding is considered to be a way to prevent urinary retention after surgery, which is of great importance in cholecystectomy. This study aimed to assess the effect of transcutaneous electrical acupoint stimulation (TEAS) on spontaneous voiding recovery after laparoscopic cholecystectom. METHODS: Participants who underwent elective laparoscopic cholecystectomy were randomly assigned to either the TEAS group or the sham group. Active TEAS or sham TEAS at specific acupuncture points was conducted intraoperatively and postoperatively. The primary outcome was the recovery speed of spontaneous voiding ability after surgery and secondary outcomes included postoperative urinary retention (POUR), voiding dysfunction, pain, anxiety and depression, and early recovery after surgery. RESULTS: A total of 1,948 participants were recruited and randomized to TEAS (n = 975) or sham (n = 973) between August 2018 and June 2020. TEAS shortens the time delay of the first spontaneous voiding after laparoscopic cholecystectomy (5.6 h [IQR, 3.7-8.1 h] in the TEAS group vs 7.0 h [IQR, 4.7-9.7 h] in the sham group) (p < 0.001). The TEAS group experienced less POUR (p = 0.020), less voiding difficulty (p < 0.001), less anxiety and depression (p < 0.001), reduced pain (p = 0.007), and earlier ambulation (p = 0.01) than the sham group. CONCLUSIONS: Our results showed that TEAS is an effective approach to accelerate the recovery of spontaneous voiding and reduce POUR which facilitates recovery for patients after laparoscopic cholecystectomy.

Andrographolide ameliorates hepatic steatosis by suppressing FATP2-mediated fatty acid uptake in mice with nonalcoholic fatty liver disease.

Excessive intrahepatocellular lipid accumulation or steatosis is caused by abnormal lipid metabolism and a common character of nonalcoholic fatty liver disease (NAFLD), which may progress into cirrhosis and hepatocellular cancer. Andrographolide (Andro) is the primary active ingredient extracted from Andrographis paniculata, showing a protective role against dietary steatosis with the mechanism not fully understood. In this study, we showed that administration of Andro (50, 100, and 200 mg/kg/day for 8 weeks, respectively) attenuated obesity and metabolic syndrome in high-fat diet (HFD)-fed mice with improved glucose tolerance, insulin sensitivity, and reduced hyperinsulinemia, hyperglycemia, and hyperlipidemia. HFD-fed mice presented hepatic steatosis, which was significantly prevented by Andro. In vitro, Andro decreased the intracellular lipid droplets in oleic acid-treated LO2 cells. The selected RT-PCR array revealed a robust expression suppression of the fatty acid transport proteins (FATPs) by Andro treatment. Most importantly, we found that Andro consistently reduced the expression of FATP2 in both the oleic acid-treated LO2 cells and liver tissues of HFD-fed mice. Overexpression of FATP2 abolished the lipid-lowering effect of Andro in oleic acid-treated LO2 cells. Andro treatment also reduced the fatty acid uptake in oleic acid-treated LO2 cells, which was blunted by FATP2 overexpression. Collectively, our findings reveal a novel mechanism underlying the anti-steatosis effect of Andro by suppressing FATP2-mediated fatty acid uptake, suggesting the potential therapeutic application of Andro in the treatment of NAFLD.

[Comparison of chemical compositions of different parts of Xanthoceras sorbifolium seeds based on UHPLC-Q-Orbitrap HRMS].

Xanthoceras sorbifolium seeds have a wide range of applications in the food and pharmaceutical industries. To compare and analyze the chemical compositions of different parts of X. sorbifolium seeds and explore the potential value and research prospects of non-medicinal parts, this study used ultra-high-performance liquid chromatography quadrupole Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) to detect the chemical composition of various parts of the seeds. A total of 82 components were preliminary identified from X. sorbifolium seeds, including 5 amino acids, 4 polyphenols, 3 phenylpropionic acids, 7 organic acids, 15 flavonoids, 6 glycosides, and 23 saponins. Mass spectrometry molecular networking(MN) analysis was conducted on the results from different parts of the seeds, revealing significant differences in the components of the seed kernel, seed coat, and seed shell. The saponins and flavonoids in the seed kernel were superior in terms of variety and content to those in the seed coat and shell. Based on the chromatographic peaks of different parts from multiple batches of samples, multivariate statistical analysis was carried out. Four differential components were determined using HPLC, and the average content of these components in the seed kernel, seed coat, and seed shell were as follows: 0.183 6, 0.887 4, and 1.440 1 mg·g~(-1) for fraxin; 0.035 8, 0.124 1, and 0.044 5 mg·g~(-1) for catechin; 0.032 9, 0.072 0, and 0.221 5 mg·g~(-1) for fraxetin; 0.435 9, 2.114 7, and 0.259 7 mg·g~(-1) for epicatechin. The results showed that catechin and fraxetin had relatively low content in all parts, while fraxin had higher content in the seed coat and seed shell, and epicatechin had higher content in the seed kernel and seed coat. Therefore, the seed coat and seed shell possess certain development value. This study provides rapid analysis and comparison of the chemical compositions of different parts of X. sorbifolium seeds, which offers an experimental basis for the research and clinical application of medicinal substances in X. sorbifolium seeds.

[Clinical observation of electroacupuncture combined with Qingyi Xianxiong Decoction in the treatment of acute respiratory distress syndrome due to severe acute pancreatitis].

OBJECTIVE: To observe the clinical effect of electroacupuncture combined with Qingyi Xianxiong Decoction on the treatment of acute respiratory distress syndrome (ARDS) caused by severe acute pancreatitis (SAP). METHODS: From February 2021 to April 2022, 120 patients with ARDS caused by SAP who were admitted to the department of critical care medicine of Tianjin Nankai Hospital and whose syndrome differentiation belonged to the syndrome of knot chest were selected. They were randomly divided into pure traditional Chinese medicine group and acupuncture medicine group, with 60 cases in each group. The pure traditional Chinese medicine group was received Qingyi Xianxiong Decoction on the basis of conventional western medicine treatment, and the acupuncture medicine group was received electric acupuncture treatment on the basis of the pure traditional Chinese medicine group. The two groups continued to be treated for 7 days. The primary outcome was the ventilator-free days within 28 days after admission to the intensive care unit (ICU), and the secondary outcome measures were mechanical ventilation time, the length of ICU stay, total lenth of hospital stay, time of intra-abdominal pressure recovery, scores of organ function, oxygenation index (PaO2/FiO2), serum inflammatory factors, blood amylase, urine amylase, etc. RESULTS: Compared with the pure traditional Chinese medicine group, the ventilator-free days in the acupuncture medicine group within 28 days after admission to the ICU were significantly longer [day: 22.10±2.29 vs. 20.97±2.31, P < 0.05, odds ratio (OR) = 1.24, 95% confidence interval (95%CI) was 1.053-1.460, P < 0.05]. The time of mechanical ventilation, the length of ICU stay, total length of hospital stay, and recovery time of intra-abdominal pressure were significantly shortened [mechanical ventilation time (days): 5.90±2.29 vs. 7.03±2.31, the length of ICU stay (days): 8.07±1.89 vs. 12.08±2.23, total length of hospital stay (days): 19.55±6.82 vs. 22.28±5.19, recovery time of intra-abdominal pressure (days): 6.05±1.81 vs. 8.45±1.76, all P < 0.05]. The Murray score and bedside index for severity in acute pancreatitis (BISAP) score of the two groups after 7 days of treatment were significantly lower than those before treatment, while PaO2/FiO2 was significantly higher than those before treatment, and the Murray score of the acupuncture medicine group after 7 days of treatment was significantly lower than that of the pure traditional Chinese medicine group [score: 0.50 (0.33, 0.75) vs. 1.00 (1.00, 1.33), P < 0.05], PaO2/FiO2 was significantly higher than that in the pure traditional Chinese medicine group [mmHg (1 mmHg ≈ 0.133 kPa): 390.75±27.73 vs. 330.02±42.34, P < 0.05]. With the prolongation of treatment time, the levels of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), serum amylase and urine amylase in both groups after treatment continued to decrease, and the levels of the inflammatory factors in the acupuncture medicine group after 7 days of treatment were significantly lower than those in the pure traditional Chinese medicine group [TNF-α (ng/L): 38.20±10.00 vs. 45.35±5.09, IL-6 (ng/L): 0.95±0.44 vs. 7.42±1.39, CRP (mg/L): 8.55±2.79 vs. 36.20±13.97, all P < 0.05]. Subgroup analysis showed that biliary system disease was a risk factor for the duration of mechanical ventilation ≥ 7 days in the treatment of ARDS with acupuncture and medicine (OR = 2.728, 95%CI was 1.293-5.754). CONCLUSIONS: Compared with the pure traditional Chinese medicine, acupuncture combined can better reduce the clinical symptoms of patients with ARDS caused by SAP, promote the recovery of patients, and reduce systemic inflammatory reaction, which is worthy of clinical promotion.

Paeoniflorin Ameliorates Colonic Fibrosis in Rats with Postinfectious Irritable Bowel Syndrome by Inhibiting the Leptin/LepRb Pathway.

Postinfectious irritable bowel syndrome (PI-IBS) is a highly prevalent gastrointestinal disorder associated with immune dysregulation and depression- and anxiety-like behaviors. Through traditional medicine, the active ingredient of Paeoniae Radix called paeoniflorin (PF) was previously found to prevent the symptoms of PI-IBS. However, there is limited information on the effects of PF on intestinal function and depression- and anxiety-like symptoms in PI-IBS animal models. Here, we aimed to determine the effects of PF treatment on the symptoms of PI-IBS in a rat model. The PI-IBS rat model was established via early postnatal sibling deprivation (EPSD), trinitrobenzenesulfonic acid (TNBS), and chronic unpredictable mild stress (CUMS) stimulation and then treated with different dosages of PF (10, 20, and 40 mg/kg) and leptin (1 and 10 mg/kg). The fecal water content and body weight were measured to evaluate the intestinal function, while the two-bottle test for sucrose intake, open field test (OFT), and elevated plus maze test (EMT) were performed to assess behavioral changes. The serum leptin levels were also measured using an enzyme-linked immunosorbent assay. Furthermore, the expressions of leptin and its receptor, LepRb, were detected in colonic mucosal tissues through an immunohistochemical assay. The activation of the PI3K/AKT signaling pathway and the expression of brain-derived neurotrophic factor (BDNF) were also detected via western blotting. After the experimental period, the PI-IBS rats presented decreased body weight and increased fecal water content, which coincided with elevated leptin levels and heightened depression- and anxiety-like behaviors (e.g., low sucrose intake, less frequency in the center areas during OFT, and fewer activities in the open arms during EMT). However, the PF treatment ameliorated these observed symptoms. Furthermore, PF not only inhibited leptin/LepRb expression but also reduced the PI3K/AKT phosphorylation and BDNF expression in PI-IBS rats. Notably, cotreatment with leptin (10 mg/kg) reduced the effects of PF (20 mg/kg) on colonic fibrosis, leptin/LepRb expression, and PI3K/AKT activation. Therefore, our findings suggest that leptin is targeted by PF via the leptin/LepRb pathway, consequently ameliorating the symptoms of PI-IBS. Our study also contributes novel insights for elucidating the pharmacological action of PF on gastrointestinal disorders and may be used for the clinical treatment of PI-IBS in the future.

Association between Outpatient Visits and Initiating Medication among Elderly Patients after an Osteoporotic Vertebral Fracture.

PURPOSE: A treatment gap exists in vertebral fracture (VF) patients. An outpatient visit is a necessary step to initiate treatment. The study aimed to evaluate factors associated with an outpatient visit following a VF diagnosis, and the association between the interval of an outpatient visit after VF diagnosis and its impact on prescribing of anti-osteoporosis medications (AOMs). METHODS: Subjects 65 years and older from Tianliao Township in Taiwan with newly diagnosed VF between 2009 and 2010 were included. Information about outpatient visits and AOMs prescriptions were derived from the National Health Insurance Research database and followed up for 2 years. Factors associated with outpatient visits and the initiation of AOMs were assessed using the multivariable Cox proportional regression model analysis. The receiver operating characteristic curve (ROC curve) was analyzed to determine the predictive effects of the interval between an outpatient visit following the diagnosis of a new VF on initiating AOMs and the potential optimal cutoff point. RESULTS: Of 393 participants, 42.2% had outpatient visits within 2 years after a new VF diagnosis, for which the mean interval was 4.8 ± 4.8 months. Patients who were female and reported a current use of supplements were positively associated with visits after a new VF diagnosis, but the bone mineral density (BMD) T-score was negatively associated with visits. Furthermore, 140 (35.6%) patients had initiated AOMs within 2 years after the diagnosis of a new VF. It was found that a higher BMD T-score and a longer interval between an outpatient visit following diagnosis was negatively associated with initiation of AOMs. The ROC curve analysis showed outpatient visits within 3 months after a VF diagnosis had the highest Youden index and maximum area under the curve. CONCLUSIONS: Patients who were female, were currently taking supplements, and those who had a lower BMD T-score were more likely to visit doctors after being diagnosed with a new VF. Furthermore, a lower BMD T-score and a shorter interval, within 3 months and not more than 8 months, between an outpatient visit following the diagnosis of VF increased the likelihood of being prescribed AOMs.

Maternal propionate supplementation ameliorates glucose and lipid metabolic disturbance in hypoxia-induced fetal growth restriction.

Intrauterine growth restriction (IUGR), one of the major complications of pregnancy, is characterized by low birth weight and results in higher risks for long-term problems including developing metabolic and cardiovascular diseases. Short-chain fatty acids (SCFAs), especially propionate, have been reported to correct glucose and lipid disorders in metabolic diseases. We hypothesized that maternal propionate supplementation could prevent glucose and lipid metabolic disturbance in hypoxia-induced IUGR. Here, in our study, maternal hypoxia was induced from gestational day (GD) 11 to GD 17.5 to establish an IUGR mouse model. Maternal propionate treatment reversed reduced birth weight in male IUGR offspring. Hepatic transcriptomics demonstrated that SP treatment significantly lowered glucose and lipid metabolism-related genes (Scd1, G6pc, Pck1 and Fasl) in IUGR offspring. KOG enrichment analysis showed that propionate-induced down-regulated differential expressed genes (DEGs) mainly belonged to lipid transport and metabolism. KEGG enrichment results showed that the down-regulated DEGs were mostly enriched in PPAR and FoxO signaling pathways. We also found that maternal oral administration of SP decreased serum lipid content, attenuated hepatic insulin resistance and liver lipid accumulation, reduced hepatic key gene expressions of gluconeogenesis and lipogenesis, increased energy expenditure and improved liver function in 11-week-old male IUGR offspring. These results indicate that maternal propionate supplementation increases birth weight and corrects hepatic glucose and lipid metabolic disturbance and energy expenditure in male mice born with IUGR, which may provide a basis for using propionate to treat IUGR disease.

The induced cryptic metabolites and antifungal activities from culture of Penicillium chrysogenum by supplementing with host Ziziphus jujuba extract.

The productions of cryptic metabolites including three undescribed drimane sesquiterpenoids, penicichrins A-C, and three known compounds from Penicillium chrysogenum were activated by the host Ziziphus jujuba medium. The structures were established by comprehensive analysis of spectroscopic data. The spiro ß-lactone, and gem-dimethyl dihydroxylation in induced penicichrins A-C were rare in natural products. Cryptic metabolites, monaspurpurone was first found in Penicillium. 4-Methoxy-3-methylgoniothalamin, and 2-hydroxy-l-phenyl-l,4-pentanedione were second example of isolation. Penicichrin A, monaspurpurone, 4-methoxy-3-methylgoniothalamin, physcion, ergosterol, and ergosta-7,22-dien-3ß-ol had antifungal activities against phytopathogens, P. chrysogenum, Alternaria alternata and Aspergillus fumigatus with MICs ≤2 µg/mL, and 2-hydroxy-l-phenyl-l,4-pentanedione had flowering activity. So the chemical constituents from Z. jujuba could induce the productions of cryptic metabolites with plant growth-promoting activity from endophyte P. chrysogenum.

Baicalein Exerts Therapeutic Effects against Endotoxin-Induced Depression-like Behavior in Mice by Decreasing Inflammatory Cytokines and Increasing Brain-Derived Neurotrophic Factor Levels.

Inflammation plays an important role in the pathophysiology of depression. This study aims to elucidate the antidepressant effect of baicalein, an anti-inflammatory component of a traditional Chinese herbal medicine (Scutellaria baicalensis), on lipopolysaccharide (LPS)-induced depression-like behavior in mice, and to investigate the underlying mechanisms. In vitro, baicalein exhibited antioxidant activity and protected macrophages from LPS-induced damage. The results of the tail suspension test and forced swimming test (tests for despair potential in mice) showed the antidepressant effect of baicalein on LPS-treated mice. It also substantially decreased the production of pro-inflammatory cytokines, including IL-6, TNF-α, MCP-1, and eotaxin, elicited by LPS in the plasma. Baicalein downregulated NF-κB-p65 and iNOS protein levels in the hippocampus, demonstrated its ability to mitigate neuroinflammation. Additionally, baicalein increased the levels of the mature brain-derived neurotrophic factor (mBDNF) in the hippocampus of LPS-treated mice, and elevated the ratio of mBDNF/proBDNF, which regulates neuronal survival and synaptic plasticity. Baicalein also promoted the expression of CREB, which plays a role in a variety of signaling pathways. In summary, the findings of this study demonstrate that the administration of baicalein can attenuate LPS-induced depression-like behavior by suppressing neuroinflammation and inflammation induced by the peripheral immune response.

[Study on alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury based on network pharmacology and cell experiments].

This study was designed to explore the alleviating effect and mechanism of Glycyrrhizae Radix et Rhizoma against Psora-leae Fructus-induced liver injury based on network pharmacology and cell experiments. The active components of Glycyrrhizae Radix et Rhizoma and Psoraleae Fructus were first retrieved from the Encyclopedia of Traditional Chinese Medicine(ETCM), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Comparative Toxicogenomics Database(CTD), and literature and further screened by SwissADME. The obtained 25 potential toxic components of Psoraleae Fructus and 29 flavonoids in Glycyrrhizae Radix et Rhizoma were input into the SwissTargetPrediction for target predication. A total of 818 targets related to liver injury were screened out based on GeneCards and MalaCards, and 91 common targets of Psoraleae Fructus, Glycyrrhizae Radix et Rhizoma, and liver injury were obtained from Venny. STRING was applied for constructing the PPI network, and Metascape for analyzing the biological processes and signaling pathways that common targets participated in. Cytoscape was used to construct the component-target-disease network and component-target-pathway network for Glycyrrhizae Radix et Rhizoma against Psoraleae Fructus-induced liver injury. The predicted core targets were proto-oncogene tyrosine-protein kinase(SRC), phosphatidylinositol 4,5-bisphosphate 3-kinase subunit alpha(PIK3 CA), RAC-alpha serine/threonine-protein kinase(AKT1), etc, with PI3 K-AKT signaling pathway, MAPK signaling pathway, apoptosis, Toll-like receptor signaling pathway, and NF-κB signaling pathway mainly involved. Following the scree-ning of the main toxic and pharmacodynamic components, the pharmacodynamic effects were investigated by cell experiments. The results showed that licochalcone A was mainly responsible for alleviating coryfolin-induced liver injury, licochalcone B for coryfolin-and psoralidin-induced liver injury, and echinatin for corylifolinin-and bakuchiol-induced liver injury. The preliminary revealing of the alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury and the prediction of related mechanisms will provide reference for further mechanism research and reasonable clinical compatibility.

Antifeedant and Antifungal Activities of Metabolites Isolated from the Coculture of Endophytic Fungus Aspergillus tubingensis S1120 with Red Ginseng.

A new globoscinic acid derivative, aspertubin A (1) along with four known compounds, were obtained from the co-culture of Aspergillus tubingensis S1120 with red ginseng. The chemical structures of compounds were characterized by using spectroscopic methods, the calculated and experimental electronic circular dichroism. Panaxytriol (2) from red ginseng, and asperic acid (4) showed significant antifeedant effect with the antifeedant rates of 75 % and 80 % at the concentrations of 50 µg/cm2 . Monomeric carviolin (3) and asperazine (5) displayed weak attractant activity on silkworm. All compounds were assayed for antifungal activities against phytopathogens A. tubingensis, Nigrospora oryzae and Phoma herbarum and the results indicated that autotoxic aspertubin A (1) and panaxytriol (2) possessed selective inhibition against A. tubingensis with MIC values at 8 µg/mL. The co-culture extract showed higher antifeedant and antifungal activities against P. herbarum than those of monoculture of A. tubingensis in ordinary medium. So the medicinal plant and endophyte showed synergistic effect on the plant disease resistance by active compounds from the coculture of A. tubingensis S1120 and red ginseng.

[Comparison on distribution of 8 components from ethanol extract of Psoraleae Fructus between normal and lipopolysaccharide-induced model rats].

UPLC-TQ/MS was employed to determine the content of 8 main components(psoralen, isopsoralen, psoralenoside, isopsoralenoside, bavachin, psoralidin, corylin, and neobavaisoflavone) in tissues of normal and lipopolysaccharide(LPS)-induced model rats 0.5, 1, 2, 6, and 12 h after intragastric administration of 3.6 g·kg~(-1) ethanol extract of Psoraleae Fructus. The distribution characteristics of the 8 main components in the different tissues(liver, kidney, spleen, heart, and lung) were studied and compared. The results showed that the distribution behaviors of the components varied among different tissues. At different time points, the components presented wide and uneven distribution in the body. Liver and kidney had higher content of the components, followed by spleen, heart, and lung. In both normal and LPS-induced model rats, the content of the 8 main components was higher in liver and kidney and varied significantly among different tissues. The content of psoralen in the tissues of LPS-induced model rat was significantly higher than that of the normal group 12 h after administration. The reason may be that the modeling slowed down the absorption and distribution of psoralen. The LPS-induced model rats had higher content of psoralenoside and isopsoralenoside in the liver tissue than the normal rats, which indicated that the modeling increased the absorption and distribution of psoralenoside and isopsoralenoside in the liver tissue. Further, it is hypothesized that psoralenoside and isopsoralenoside may be toxic substances of Psoraleae Fructus-induced liver injury.

Berberine attenuates atherosclerotic lesions and hepatic steatosis in ApoE-/- mice by down-regulating PCSK9 via ERK1/2 pathway.

BACKGROUND: It has been demonstrated that berberine (BBR), a kind of alkaloid derived from Chinese herbal medicine, has multiple pharmacological effects on human's diseases including anti-atherosclerosis action. However, although the previous studies showed that the beneficial impact of BBR on atherosclerosis might be associated with proprotein convertase subtilisin/kexin type 9 (PCSK9), the exact underlying mechanism are not fully determined. The present study aimed to investigate potential mechanisms of anti-atherosclerosis by BBR using ApoE-/- mice. METHODS: The eight-week mice were divided into five groups: group 1 (wild type C57BL/6J mice with normal diet), group 2 (ApoE-/- mice with normal diet), group 3 [ApoE-/- mice with high-fat diet (HFD)], group 4 (ApoE-/- mice with HFD, and treatment with low dose BBR of 50 mg/kg/d), and group 5 (ApoE-/- mice with HFD, and treatment with high dose BBR of 100 mg/kg/d). After a 16-week treatment, the blood sample, aorta and liver were collected for lipid analysis, hematoxylin-eosin (HE) or oil red O staining, and Western blotting respectively. Besides, HepG2 Cells were cultured and treated with different concentrations of BBR (0, 5, 25 and 50 µg/mL) for 24 hours. Subsequently, cells were collected for real-time PCR or western blotting assays. Finally, the expression levels of PCSK9, LDL receptor (LDLR), ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor class B type I (SR-BI) were examined. RESULTS: Fifty mg/kg/d and 100 mg/kg/d of BBR decreased total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) cholesterol (LDL-C), and increased high-density lipoprotein cholesterol (HDL-C) level. Moreover, BBR reduced aorta atherosclerotic plaque, and ameliorated lipid deposition in ApoE-/- mice fed with HFD. Finally, in vitro study showed that BBR promoted intracellular cholesterol efflux, up-regulated LDLR and down-regulated PCSK9 expression via the ERK1/2 pathway in cultured HepG2 cells. CONCLUSIONS: Data indicated that BBR significantly attenuated lipid disorder, reduced aortic plaque formation, and alleviated hepatic lipid accumulation in ApoE-/- mice fed with HFD, which was associated with down-regulation of PCSK9 through ERK1/2 pathway.

Lycibarbarines A-C, Three Tetrahydroquinoline Alkaloids Possessing a Spiro-Heterocycle Moiety from the Fruits of Lycium barbarum.

Three tetrahydroquinoline alkaloids, lycibarbarines A-C (1-3), possessing a unique tetracyclic tetrahydroquinoline-oxazine-ketohexoside fused motif, were isolated from the fruits of Lycium barbarum. Their structures were determined by spectroscopic analysis and quantum-chemical calculations. Compounds 1 and 3 exhibited neuroprotective activity when evaluated for corticosterone-induced injury by reducing the apoptosis of PC12 cells through the inhibition of caspase-3 and caspase-9.

Anti-obesity effect of Liupao tea extract by modulating lipid metabolism and oxidative stress in high-fat-diet-induced obese mice.

Liupao tea (LPT) is traditional dark Chinese tea. The effect of LPT extract on high-fat-diet-induced obese mice was investigated systematically. The results showed that LPT extract could reduce body weight and significantly alleviate liver damage and fat accumulation. LPT could also decrease the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (AKP), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) and increase the level of high-density lipoprotein cholesterol (HDL-C) in the liver. It also decreased the serum levels of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin (IL)-1ß, and IL-6 and increased the serum levels of anti-inflammatory cytokines, including IL-10 and IL-4. Moreover, LPT improved the levels of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) and reduced the level of malondialdehyde (MDA) in the liver. Moreover, LPT could upregulate the mRNA and protein expressions of peroxisome proliferator-activated receptor alpha (PPAR-α), lipoprotein lipase (LPL), carnitine palmitoyltransferase 1(CPT1), and cholesterol 7 alpha-hydroxylase (CYP7A1) and downregulate those of PPAR-γ and CCAAT/enhancer-binding protein alpha (C/EBP-α) in the liver. It also increased the mRNA expression of copper/zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), CAT, gamma-glutamylcysteine synthetase 1 (GSH1), and GSH-Px. The components of LPT extract include catechin, rutin, taxifolin, and astragalin, which possibly have a wide range of biological activities. In conclusion, our work verified that LPT extract possessed an anti-obesity effect and alleviated obesity-related symptoms, including lipid metabolism disorder, chronic low-grade inflammation, and liver damage, by modulating lipid metabolism and oxidative stress.

Malus hupehensis leaves extract attenuates obesity, inflammation, and dyslipidemia by modulating lipid metabolism and oxidative stress in high-fat diet-induced obese mice.

Malus hupehensis leaves (MHL) are used to make traditional Chinese tea. In this study, MHL extract was shown to improve metabolic disorders and inflammatory response in high-fat diet-induced obese mice. MHL extract could reduce body weight, and significantly alleviate liver damage and fat accumulation. MHL extract caused a decrease in the levels of ALT, AST, AKP, TC, TG, LDL-C, and an increase in the level of HDL-C. It also caused a decrease in inflammatory cytokines, including TNF-α, IFN-γ, IL-1ß, IL-6, and an increase in the anti-inflammatory cytokine IL-10 and IL-4. MHL extract could upregulate mRNA expression of PPAR-α, LPL, CPT1, CYP7A1, SOD1, SOD2, CAT, GSH1, and GSH-Px and downregulate that of PPAR-γ and C/EBP-α in the liver of obese mice. In conclusion, our work represents the first study demonstrating that MHL extract possesses an anti-obesity effect and alleviates obesity-related symptoms, including dyslipidemia, chronic low-grade inflammatory, and liver damage. PRACTICAL APPLICATIONS: The research may contribute to the development and application of MHL as functional foods or dietary supplement to fight against obesity.

Combination of Quercetin, Hirudin and Cinnamaldehyde Promotes Schwann Cell Differentiation and Myelination against High Glucose by Inhibiting ERK Signaling Pathway.

OBJECTIVE: To investigate the therapeutic and synergistic effects of QHC (combination of quercetin (Q), hirudin (H) and cinnamaldehyd (C)) on Schwann cell differentiation and myelination against high glucose (HG) induced injury. METHODS: Primary-culture Schwann cells exposed to HG (50 mmol/L) for 72 h and Schwann cell-dorsal root ganglion (DRG) neuron cocultures exposed to HG (50 mmol/L) for 7 days were employed as in vitro model of diabetic neuropathy. The cells were randomly divided into 10 groups: control (CON, 25 mmol/L glucose), HG (50 mmol/L glucose), HG plus 10 µmol/L quercetin (Q), HG plus 0.04 IU/mL hirudin (H), HG plus 100 nmol/L cinnamaldehyd (C), HG plus 10 µmol/L quercetin and 0.04 IU/mL hirudin (QH), HG plus 10 µmol/L quercetin and 50 nmol/L cinnamaldehyd (QC), HG plus 0.04 IU/mL hirudin and 50 nmol/L cinnamaldehyd (HC), HG plus 10 µmol/L quercetin, 0.04 IU/mL hirudin and 50 nmol/L cinnamaldehyd (QHC) or 10 µmol/L U0126. Cell differentiation was evaluated by periaxin immunofluorescence staining. The protein expression levels of myelin protein zero (P0), myelin basic protein (MBP), myelin-associated glycoprotein (MAG), extracellular signal-regulated kinase (ERK), p-ERK, p-c-Jun, c-Jun, notch intracellular domain (NICD) and the mRNA expression levels of P0, MBP, MAG, Krox-20, Notch1 and Jagged1 were detected by Western blotting and real-time quantitative PCR analysis. The secretion of ciliary neurotrophic factor (CNTF) was determined by enzyme-linked immunosorbent assay (ELISA). The number and length of the myelin segments were evaluated by MBP immunofluorescence staining. The expression and the location of p-ERK in cocultures were detected by MAG and p-ERK immunofluorescence double staining. RESULTS: Co-treatment with Q, C, H and their combination promoted Schwann cell differentiation, increased CNTF secretion, up-regulated the protein and mRNA expressions of myelin, and increased the number and length of the myelin segments (P<0.01 or P<0.05). In particular, the combination therapy of Q, H and C was superior to the respective monotherapy (P<0.01). Combination therapy of QHC exhibited higher inhibitory activities for ERK signaling related molecules than each monomer or the combination of the two monomers (P<0.01). CONCLUSION: QHC combination yielded synergy in promoting Schwann cell differentiation and myelination and the protective effect may involve in the inhibition of ERK signaling pathway, providing scientific evidence for better understanding of combination of Q, H and C in clinical applications.