Integrated metabolomics and network pharmacology study on the mechanism of herbal pair of danggui-kushen for treating ischemia heart disease.

DangGui-KuShen (DK) is a well-known classic traditional Chinese medicine recipe that improves blood circulation, eliminates moisture, and detoxifies, and is frequently used in the treatment of cardiovascular problems. Some protective effects of DK on cardiovascular disease have previously been identified, but its precise mechanism remains unknown. The goal of this study is to combine metabolomics and network pharmacology to investigate DK's protective mechanism in Ischemic Heart Disease(IHD) rat models. A combination of metabolomics and network pharmacology based on UPLC-Q-TOF/MS technology was used in this study to verify the effect of DK on IHD through enzyme-linked immunosorbent assay, HE staining, and electrocardiogram, and it was determined that DK improves the synergistic mechanism of IHD. In total, 22 serum differential metabolites and 26 urine differential metabolites were discovered, with the majority of them involved in phenylalanine, tyrosine, and tryptophan biosynthesis, glycine, serine, and threonine metabolism, arginine and proline metabolism, aminoacyl-tRNA biosynthesis, purine metabolism, and other metabolic pathways. Furthermore, using network pharmacology, a composite target pathway network of DangGui and KuShen for treating IHD was created, which is primarily associated to the tumor necrosis factor (TNF) signaling pathway, P53 signaling, and HIF-1 signaling pathways. The combined research indicated that the NF-B signaling pathway and the HIF-1 signaling pathway are critical in DK treatment of IHD. This study clearly confirms and expands on current knowledge of the synergistic effects of DG and KS in IHD.

Cancer SLC6A6-mediated taurine uptake transactivates immune checkpoint genes and induces exhaustion in CD8+ T cells.

Taurine is used to bolster immunity, but its effects on antitumor immunity are unclear. Here, we report that cancer-related taurine consumption causes T cell exhaustion and tumor progression. The taurine transporter SLC6A6 is correlated with aggressiveness and poor outcomes in multiple cancers. SLC6A6-mediated taurine uptake promotes the malignant behaviors of tumor cells but also increases the survival and effector function of CD8+ T cells. Tumor cells outcompete CD8+ T cells for taurine by overexpressing SLC6A6, which induces T cell death and malfunction, thereby fueling tumor progression. Mechanistically, taurine deficiency in CD8+ T cells increases ER stress, promoting ATF4 transcription in a PERK-JAK1-STAT3 signaling-dependent manner. Increased ATF4 transactivates multiple immune checkpoint genes and induces T cell exhaustion. In gastric cancer, we identify a chemotherapy-induced SP1-SLC6A6 regulatory axis. Our findings suggest that tumoral-SLC6A6-mediated taurine deficiency promotes immune evasion and that taurine supplementation reinvigorates exhausted CD8+ T cells and increases the efficacy of cancer therapies.

Effects and core patterns of Chinese herbal medicines on hematologic manifestations in systemic lupus erythematosus: A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of Chinese herbal medicines (CHMs) on hematologic manifestations in patients with systemic lupus erythematosus (SLE). DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Airiti Library were searched for the period January 2000 to February 2022. STUDY SELECTION: RCTs involving CHMs in patients with SLE with available hematologic data. DATA EXTRACTION: The primary outcomes included white blood cell (WBC) count, hemoglobin level, and platelet count. The Cochrane risk of bias tool was used to assess the quality of the included RCTs. Sensitivity analysis of RCTs with abnormal hematologic data before intervention was performed to verify the robustness of the results. Subgroup analysis was also applied for results with high heterogenicity. Core patterns of used herbal drug pairs had also been analyzed and visualized. DATA SYNTHESIS: Fifteen RCTs involving 1183 participants were included. The effects of elevating WBC count (weighted mean difference [WMD]: 0.69; 95% confidence interval [CI]: 0.33-1.06; p <0.001), hemoglobin levels (WMD: 0.64; 95% CI: 0.31-0.97; p <0.001), and platelet count (WMD: 0.61; 95% CI: 0.48-0.74; p <0.001) in the CHM group were significantly greater than those in the control group. In total, 23 single herbs and 152 herbal drug pairs were identified for core patterns network analysis. CONCLUSIONS: We demonstrated significantly superior therapeutic effects achieved with CHMs and conventional therapy regarding leukopenia, anemia, and thrombocytopenia compared to that of conventional therapy alone in patients with SLE.

Different ratios of Schisandra chinensis and Evodia rutaecarpa combination for treating Alzheimer's disease.

Schisandra chinensis and Evodia rutaecarpa are traditional Chinese herbs that have been used for many years to treat neurodegenerative diseases. In Chinese medicine, multiple herbs are often used in combination to enhance their efficacy, and different combination ratios can produce different therapeutic effects, thus flexibly responding to the needs of various patients. This study aimed to investigate the effects of different ratios of Schisandra and Evodia herbs on learning and memory impairment in rats with Alzheimer's disease (AD) and their specific mechanisms of action. Morris water maze and hematoxylin and eosin (HE) staining experiments were performed to evaluate the effects of different ratios of Schisandra-Evodia on learning memory in AD model rats. Immunohistochemical experiments were performed to investigate the effects of Schisandra-Evodia on the Aß1-42 and P-Tau proteins, and protein immunoblotting (WB) was performed to determine the expression of key proteins in two pathways, BDNF/TrkB/CREB and GSK-3ß/Tau. Our experimental results show that all Schisandra-Evodia groups showed significant neuroprotective effects, improved learning memory impairment, and reduced levels of Aß1-42 and P-Tau proteins in AD model rats. Schisandra-Evodia upregulated BDNF, P-TrkB/TrkB, and P-CREB/CREB protein expression and downregulated GSK-3ß and P-Tau/Tau protein expression. Among the different Schisandra-Evodia ratio groups, the 2:1 group showed the strongest therapeutic effect on AD. Our research results indicate that Schisandra-Evodia can reduce Aß1-42 and P-Tau protein content by modulating the activity of two pathways, BDNF/TrkB/CREB and GSK-3ß/Tau, thus improving neuronal cell damage and cognitive deficits caused by AD. In addition, we found that a Schisandra-Evodia ratio of 2:1 had the most profound therapeutic effect on AD.

Characterization of chemical constituents and metabolites in vivo and in vitro after oral administration of Wuteng tablets in rats by UHPLC-Q/TOF-MS.

Waste medicinal plants are widely used in drug production. With the increasing demand for botanical drugs, there is an urgent need to identify new and effective drugs and improve the utilization of medicinal plant resources. Wuteng tablets (WTP) are extracted from the stem of Schisandra chinensis and have a good therapeutic effect on Alzheimer's disease. In this study, a holistic identification strategy based on UHPLC-Q/TOF-MS was developed for the first time to investigate the metabolites and metabolic pathways involved in the in vitro metabolism and liver microsomal incubation and in the in vivo metabolic system of rats after WTP administration. After the oral administration of WTP, 21 metabolites were identified in the serum and 25 metabolites were identified in the urine, of which six were new metabolites; 33 metabolites were inferred from the microsomal metabolites in vitro. The metabolic pathways related to WTP mainly involve demethylation, hydroxylation, dehydroxylation and dehydrogenation. In this study, the metabolites and metabolic pathways of WTP were elucidated via UHPLC-Q/TOF-MS, which provided a basis for an in-depth study of the pharmacodynamic and pharmacotoxicological effects of WTP.

Structurally diverse polycyclic polyprenylated acylphloroglucinols with protective effect on human vein endothelial cells injured by high-glucose from Hypericum acmosepalum N. Robson.

Hyperacmotone A, a polycyclic polyprenylated acylphloroglucinol (PPAP) with an unprecedented skeleton, along with five undescribed congeners and eleven reported ones, was isolated from Hypericum acmosepalum. Hyperacmotone A possesses a unique monocyclic ring skeleton based on a cyclopent-4-ene-1,3-dione acylphloroglucinol core. Their structures were elucidated by extensive analysis of HRESIMS, NMR, biogenetic pathway, and quantum-chemical calculations. In addition, hypercohone G exhibited significant protective effects on high-glucose-injured HUVECs.

Combined exogenous selenium and biochemical fulvic acid reduce Cd accumulation in rice.

Paddy soil Cd contamination and the related accumulation risk in rice grains have attracted global attention. The application of selenium and humic substances is considered to be a cost-effective Cd mitigation measure. However, the effect of a combined application of the two materials remains unclear. Therefore, a 2-season pot experiment was conducted, wherein sodium selenite (Se) and biochemical fulvic acid (BFA) were applied alone and together. Paddy soils with two levels of Cd contamination were used. The results indicate that Se application alone considerably decreased the rice grain Cd content by 36.1-48.7% compared to the control rice grain Cd concentration, which was above the food safety limit (0.2 mg kg-1). Although the application of BFA alone decreased the soil pH, it also increased the soil CaCl2 extractable Cd content by 0.2 to 19.3% and had a limited effect on Cd in the rice grains. The combined application of Se and BFA did not affect the soil pH or the CaCl2 extractable Cd, and more effectively reduced the Cd contents of the rice grains by 50.2 to 57.1%, except for the control rice grain Cd content, which was below the limit. The combined application of Se and BFA also inhibited Se accumulation in rice grains, maintaining the Se content at a safe level (0.33-0.58 mg kg-1) compared to Se application alone. The effects of reducing the Cd content of rice grains while safely increasing their Se contents could persist for at least two seasons. Therefore, the combined application of Se and BFA should be recommended to mitigate Cd contamination risks in Cd-contaminated paddy soil.

Effect and mechanism of "Danggui-kushen" herb pair on ischemic heart disease.

AIMS: The purpose of this study was to investigate the mechanism and effects of "Danggui-kushen" herb pair (DKHP) better than single drug in ischemic heart disease (IHD). METHODS: IHD model was established by left anterior descending branch of coronary artery in rats. Rats were randomized into six groups and oral administration for 7 days: control, model, Danshen dripping pills (DS) (5.103 g/kg), Danggui (DG) (2.7 g/kg), Kushen (KS) (2.7 g/kg) and DKHP (2.7 g/kg). Electrocardiogram (ECG), myocardial infarction and damage assessment, histological inspection analysis, and various biochemical indexes of myocardial tissue were measured to evaluate the myocardial damage and the protective effects of drugs. The inflammatory levels were identified by HE staining and serum cytokine, and the expression of hypoxia-inducible factor 1α (HIF-1α), inhibitor kappa B kinaseß (IKKß) and nuclear transcription factor kappa B (NF-κB) were measured by immunohistochemistry. KEY FINDINGS: The results suggested that: compared with the control group, model group showed significantly myocardial tissue abnormalities, and increased levels of inflammatory cytokine. Treatment with drugs inhibited the increase of α-hydroxybutyrate dehydrogenase (α-HBDH), creatine kinase (CK), creatinekinase isoenzyme (CK-MB), interleukin 1 (IL-1) and interleukin 6 (IL-6). The results of immunohistochemical showed that drugs-treatment inhibited the expression of IKKß and the P-p65, increased the expression of HIF-1α, which demonstrated that the anti-inflammatory effects of DKHP was achieved by suppressing of NF-κB signaling. CONCLUSION: These observations indicated that DKHP can ameliorate myocardial injury better than single. And these are related to the inhibition of NF-κB and actives HIF-1α signaling.

18[Formula: see text]-Glycyrrhetinic Acid Inhibits TGF-[Formula: see text]-Induced Epithelial-to-Mesenchymal Transition and Metastasis of Hepatocellular Carcinoma by Targeting STAT3.

18[Formula: see text]-glycyrrhetinic acid (GA) is the active ingredient of the traditional Chinese medicinal herb Glycyrrhizae radix et rhizoma. We previously demonstrated that GA inhibited tumor growth in hepatocellular carcinoma (HCC). However, the effect of GA on transforming growth factor-[Formula: see text] (TGF-[Formula: see text]-induced epithelial-mesenchymal transition (EMT) and metastasis were still unclear. In this study, in vitro transwell assays and immunofluorescence (IF) demonstrated that GA inhibited TGF-[Formula: see text]-induced migration, invasion and EMT of HCC cells. However, it had little effect on the inhibition of proliferation by TGF-[Formula: see text]. Moreover, we confirmed that GA suppressed the metastasis of HCC cells in vivousing an ectopic lung metastasis model. Furthermore, we found that GA inhibited TGF-[Formula: see text]-induced EMT mainly by reducing the phosphorylation of signal transducer and activator of transcription 3 (STAT3), which played an essential role in TGF-[Formula: see text]-induced EMT and cell mobility. Mechanistically, GA inhibited the phosphorylation of STAT3 by increasing the expression of Src homology 2 domain-containing protein tyrosine phosphatases 1 and 2 (SHP1 and SHP2). Therefore, we concluded that GA inhibited TGF-[Formula: see text]-induced EMT and metastasis via the SHP1&SHP2/STAT3/Snail pathway. Our data provide an attractive therapeutic target for future multimodal management of HCC.

Integrative Therapy Combining Chinese Herbal Medicines With Conventional Treatment Reduces the Risk of Cardiovascular Disease Among Patients With Systemic Lupus Erythematosus: A Retrospective Population-Based Cohort Study.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that involves multiple systems and organs. Advanced conventional treatment does not appear to markedly reduce the risk of cardiovascular disease (CVD) among patients with SLE. Chinese medicine is a complementary and alternative medicine system, and some SLE patients in Taiwan also use Chinese herbal medicines (CHMs). Thus, we aimed to investigate whether integrative therapy combining CHMs with conventional therapy reduces the risk of CVD among patients with SLE. We performed a 12-years population-based retrospective cohort study using the "Systemic Lupus Erythematosus Health Database" of the National Health Insurance Research Database (NHIRD) in Taiwan. Patients newly diagnosed with SLE between 2004 and 2013 were divided into CHM and non-CHM groups and followed up until the end of 2015. We applied 1:1 individual matching by age, gender, and year of being newly diagnosed with SLE; accordingly, 2,751 patients were included in both CHM and non-CHM groups after matching. We applied the Cox proportional hazard regression model to determine the risk of CVD in relation to CHM use. During the follow-up period, 407 patients in the CHM group and 469 patients in the non-CHM group developed CVD, with incidence rates of 337 and 422 per 10,000 person-years, respectively. The Cox proportional hazards model demonstrated a significantly decreased risk of CVD among SLE patients using CHMs (adjusted HR: 0.83; 95% CI 0.73-0.95; p = 0.008). Further analyses of different types of CVDs also showed a significantly decreased risk of ischemic stroke in the CHM group (adjusted HR: 0.74; 95% CI 0.57-0.97; p = 0.032). Among the frequently used single herbs and polyherbal formulas, Shu-Jing-Huo-Xue-Tang was associated with a significantly decreased risk of CVD (adjusted HR: 0.76; 95% CI 0.58-0.99; p = 0.041). In conclusion, CHM use reduced the risk of CVD among patients with SLE in Taiwan. Further randomized studies may be needed to determine the definite causal relationship between CHM use and its protective effects against CVD among patients with SLE.

Application of ultrasound during electrode implantation for sacral neuromodulation in patients with neurogenic bladder secondary to spinal cord disease: a retrospective study.

PURPOSE: To compare the use of intraoperative ultrasound with X-ray fluoroscopy during sacral neuromodulation lead electrode placement in patients with neurogenic bladder secondary to spinal cord disease. METHODS: We reviewed the medical records of 52 patients who underwent sacral neuromodulation (SNM) lead electrode implantation under fluoroscopy or ultrasound guidance from July 2016 to July 2019. The operating time, number of electrode contacts with stimulus responses, minimum voltage that causes a stimulus response, and rate of standard lead electrode placement were used to assess the differences between the two methods. All patients were evaluated by recording bladder diaries, postvoid residual volumes before and during the testing period. Permanent SNM implantation is acceptable if symptoms improve by at least 50%. RESULTS: The operating time decreased from 87.1 ± 25.19 min in the X-ray group to 68.2 ± 25.20 min (p < 0.05) in the ultrasound group. The number of electrode contacts with stimulus responses, rate of standard lead electrode placement, and implantable pulse generator (IPG) placement rate were not significantly different between the two groups (p > 0.05). There was no radiation exposure during the operation in the ultrasound group. No incisional infections, hematomas, or other critical complications were reported in either groups. CONCLUSION: Ultrasound can be applied to safely place lead electrode for sacral neuromodulation and leads to no radiation exposure to the patient, surgeon, and operating room staff and a shortened operating time while maintaining the same efficacy as X-ray.

Hepatoprotective activity assessment of amino acids derivatives of picroside I and II.

Picrorhiza kurroa has a long medicinal history as a traditional medicinal plant in China and India that is widely used in clinical treatments. It is a common treatment for liver diseases, fever, diarrhoea, indigestion, and some other diseases. Modern pharmacological studies proved that P. kurroa rhizomes have high levels of picroside I and II, which were identified as main constituents with anti-inflammatory and hepatoprotective activities. In our study, we used picroside I and II as the lead compounds to generate derivatives by reactions with Boc-valine or Boc-proline, which underwent dehydration and condensation with the hydroxyl groups in the lead compounds in the presence of coupling reagent N,N'-dicyclohexylcarbodiimide. We synthesized 11 derivatives and examined their hepatoprotective effects in vitro by assessing the proliferation rates of H2 O2 -exposed HepG2 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. We found that some derivatives promoted higher proliferation rates in HepG2 cells than the natural compounds before derivatization, suggesting that those derivatives possessed an improved hepatoprotective capacity. The novel derivatization strategy for picrosides had the additional benefit that the esterification of their hydroxyl groups created derivatives not only with increased stability but also with improved pharmacokinetic properties and potentially prolonged half-life.

An innovative method for screening and evaluating the degree of diabetic retinopathy and drug treatment based on artificial intelligence algorithms.

Current methods of evaluating the degree of diabetic retinopathy are highly subjective and have no quantitative standard. To objectively evaluate the slight changes in tissue structure during the early stage of retinal diseases, a subjective interpretation and qualitative analysis of the pathological sections of retinal HE in diabetic animals is required for screening and evaluating the degree of diabetic retinopathy and drug efficacy. To develop an innovative method for screening and evaluating the degree of diabetic retinopathy and drug treatment based on artificial intelligence algorithms. Based on the change law of the early nerve fiber layer and the ganglion cells, we get disparate characteristics of the microscopic image of diabetes animal retina HE slices. Using image recognition and deep learning methods on these HE slices, we can identify the changes in the ganglion cells and nerve fiber layer for diagnosing early retinopathy and evaluated the therapeutic effect of the potential drugs. We conduct quantitative calculation per unit length of the nerve fiber layer and total area of the nerve fiber layer to identify biology significance of edema. Additionally, we also perform quantitative calculation with the number of unit area ganglion cells to identify the section in biology cell hyperplasia. Finally, we get the significance of quantitative calculation on the unit cell area to identify ganglion cell shriveling in biology. In addition to the evaluation of the disease degree and changes, we also obtained retinal HE sections after different drug interventions and evaluated the therapeutic effect of the drugs. This study presents a novel quantitative method for screening and evaluating of diabetic retinopathy and drug efficacy.

The risk of coronary artery disease in patients with rheumatoid arthritis using Chinese herbal products and conventional medicine in parallel: a population-based cohort study.

BACKGROUND: Few studies have evaluated the association between the risk of coronary artery disease (CAD) and the use of Chinese herbal products (CHP) in patients with rheumatoid arthritis (RA). This study investigated the risk of CAD among patients with RA using CHP in combination with conventional medicine. METHODS: A retrospective cohort study was conducted using the Taiwan National Insurance Research Database to assess 22,353 patients who had been newly diagnosed with RA between 1997 and 2010. Patients were assigned to the CHP group or non-CHP group according to their use or nonuse of CHP after being diagnosed with RA. The Cox proportional hazards model was used to estimate the hazard ratio (HR) of CAD for a 1:1 matched sample. RESULTS: Both the CHP and non-CHP groups comprised 4889 patients after 1:1 matching. The risk of CAD was significantly reduced in the CHP group [adjusted HR (aHR): 0.59, 95% confidence interval (CI): 0.50-0.71] compard with the non-CHP group. Those who used CHP for > 180 days had an even lower risk of CAD than users with CHP usage less than 30 days (aHR: 0.64, 95% CI: 0.43-0.95). Additionally, frequently prescribed formulae, such as Kuei-Chih-Shao-Yao-Chih-Mu-Tang, Tang-Kuei-Nien-Tung-Tang, and Shu-Ching-Huo-Hsieh-Tang, were associated with a reduced risk of CAD. CONCLUSION: The use of CHP was associated with a lower risk of CAD in patients with RA. Additional randomized controlled trials are required to assess any causal relationship between the effect of CHP usage and the risk of CAD.

Resection might be a meaningful choice for hepatocellular carcinoma with portal vein thrombosis: A systematic review and meta-analysis.

BACKGROUND: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, the presence of portal vein tumor thrombosis (PVTT) is considered to indicate an advanced stage of hepatocellular carcinoma (HCC) with nearly no cure. Hepatic resection and transarterial chemoembolization (TACE) have recently been recommended for treatment of HCC with PVTT. METHODS: We conducted a systematic review to compare the overall survival between patients with HCC and PVTT undergoing hepatectomy, TACE or conservative treatment including sorafenib chemotherapy. The PubMed, Web of Science, and Cochrane Library databases were searched. All relevant studies were considered. Hazard ratios with 95% confidence intervals were calculated for comparison of the cumulative overall survival. Ten retrospective studies met the inclusion criteria and were included in the review. RESULTS: Overall survival was not higher in the hepatectomy group than TACE group. But survival rate was higher in hepatectomy group than conservative group. The subgroup analysis demonstrated that hepatectomy was superior in patients without PVTT in the main trunk than in patients with main portal vein invasion. In patients without main PVTT, hepatectomy has showed more benefit than TACE. However, there has been no significant difference between the hepatectomy and TACE groups among patients with main PVTT. CONCLUSION: For patients with resectable HCC and PVTT, hepatectomy might be more effective in patients without PVTT in the main trunk than TACE or conservative treatment.

Brain activity regulates loose coupling between mitochondrial and cytosolic Ca2+ transients.

Mitochondrial calcium ([Ca2+]mito) dynamics plays vital roles in regulating fundamental cellular and organellar functions including bioenergetics. However, neuronal [Ca2+]mito dynamics in vivo and its regulation by brain activity are largely unknown. By performing two-photon Ca2+ imaging in the primary motor (M1) and visual cortexes (V1) of awake behaving mice, we find that discrete [Ca2+]mito transients occur synchronously over somatic and dendritic mitochondrial network, and couple with cytosolic calcium ([Ca2+]cyto) transients in a probabilistic, rather than deterministic manner. The amplitude, duration, and frequency of [Ca2+]cyto transients constitute important determinants of the coupling, and the coupling fidelity is greatly increased during treadmill running (in M1 neurons) and visual stimulation (in V1 neurons). Moreover, Ca2+/calmodulin kinase II is mechanistically involved in modulating the dynamic coupling process. Thus, activity-dependent dynamic [Ca2+]mito-to-[Ca2+]cyto coupling affords an important mechanism whereby [Ca2+]mito decodes brain activity for the regulation of mitochondrial bioenergetics to meet fluctuating neuronal energy demands as well as for neuronal information processing.

Oxymatrine exhibits anti-neuroinflammatory effects on Aß1-42-induced primary microglia cells by inhibiting NF-κB and MAPK signaling pathways.

Oxymatrine (OMT), isolated from Sophora flavescens or Sophora alopecuroides, possesses various pharmacological and biological activities, including anti-inflammatory, anti-oxidant, and anti-diabetic properties. Microglia cells, the resident immune cells in the central nervous system (CNS), play a key role in neurodegenerative diseases. In this study, the neuroinflammatory effects of OMT and its mechanisms were investigated by Aß1-42-induced rat brain tissue model and primary microglia cells model. The hematoxylin-eosin (HE) staining and immunohistochemistry results showed that OMT could reduce neuronal damage and inhibit microglia activation in the model tissue. The in vitro experiments revealed that OMT could decrease the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and nitric oxide (NO), and down-regulate the expression of iNOS and COX-2 in a dose-dependent manner. Furthermore, OMT inhibited phosphorylation of JNK, ERK 1/2, P-p38 and NF-κB in Aß1-42-induced microglia cells. In summary, OMT exhibits anti-neuroinflammatory effects and the anti-inflammatory activity of OMT is related to the regulation of MAPK and NF-κB signaling pathways.

The developmental expression of metabotropic glutamate receptor 4 in prenatal human frontal lobe and neurogenesis regions.

BACKGROUNDS: Metabotropic glutamate receptors, besides ionotropic receptors, mediate the complicated effect of glutamate on neurogenesis. Previous studies showed that metabotropic glutamate receptor 4 (mGluR4) regulated the proliferation and differentiation of neural stem/progenitor cells in vitro. However, little is known about the expression pattern of mGluR4 on prenatal central nervous system in vivo, especially the human being. METHODS: The normal brain tissues of human fetus were collected and divided into 4 groups according to the gestational age: 9-11 W, 14-16 W, 22-24 W and 32-36 W. Then the expression of mGluR4 was evaluated at mRNA and protein levels by means of PCR or immunohistochemistry method, respectively. The type of cell expressing mGluR4 was further investigated using double-labeling immunofluorescence. RESULTS: RT-PCR showed that the mRNA of mGluR4 could be detected in frontal lobe from 9 W to 32 W and real-time PCR quantificationally demonstrated the mRNA increased with development. Similarly, immnoreactivity was found in all layers of frontal lobe, VZ/SVZ. The intensity scores analysis showed that the staining became stronger and the range extended gradually with development. The double-labeling immunofluorescence showed that mGluR4 was present in neural stem/progenitor cells (nestin-positive cells after 9 W), young neurons (DCX-positive cells after 9 W), mature neurons (NeuN-positive cells in cortex after 32 W), as well as typical astrocytes (GFAP-positive cells in medulla after 32 W). CONCLUSION: These results supply an important evidence that mGluR4 is expressed in prenatal human cerebrum, and main kinds of cells related to neurogenesis are involved in its expression.

Oxymatrine attenuates amyloid beta 42 (Aß1-42)-induced neurotoxicity in primary neuronal cells and memory impairment in rats.

Amyloid beta 42 (Aß1-42)-induced oxidative stress causes the death of neuronal cells and is involved in the development of Alzheimer's disease. Oxymatrine (OMT) inhibits oxidative stress. In this study, we investigated the effect of OMT on Aß1-42-induced neurotoxicity in vivo and in vitro. In the Morris water maze test, OMT significantly decreased escape latency and increased the number of platform crossings. In vitro, OMT markedly increased cell viability and superoxide dismutase activity. Moreover, OMT decreased lactate dehydrogenase leakage, malondialdehyde content, and reactive oxygen species in a dose-dependent manner. OMT upregulated the ratio of Bcl-2/Bax and downregulated the level of caspase-3. Furthermore, OMT inhibited the activation of MAP kinase (ERK 1/2, JNK) and nuclear factor κB. In summary, OMT may potentially be used in the treatment of Alzheimer's disease.

Synthesis and biological evaluation of picroside derivatives as hepatoprotective agents.

Picrorhizae Rhizoma as a hepatoprotective herb, has been applied for thousands of years, and picroside was proved to be its active constituent. In this study, twelve derivatives of picroside were synthesized and the hepatoprotective activity of the derivatives was evaluated on SMMC-7721 cells. Six out of the derivatives had shown a better protective effect on H2O2-induced SMMC-7221 cells than picroside, and the activity of two derivatives (2 and 4) was stronger than that of the reference compound, silybin. Compound 2 shown the strongest protective effect (EC50 = 6.064 ± 1.295 µM).