Understanding Sorafenib-Induced Cardiovascular Toxicity: Mechanisms and Treatment Implications.

Tyrosine kinase inhibitors (TKIs) have been recognized as crucial agents for treating various tumors, and one of their key targets is the intracellular site of the vascular endothelial growth factor receptor (VEGFR). While TKIs have demonstrated their effectiveness in solid tumor patients and increased life expectancy, they can also lead to adverse cardiovascular effects including hypertension, thromboembolism, cardiac ischemia, and left ventricular dysfunction. Among the TKIs, sorafenib was the first approved agent and it exerts anti-tumor effects on hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) by inhibiting angiogenesis and tumor cell proliferation through targeting VEGFR and RAF. Unfortunately, the adverse cardiovascular effects caused by sorafenib not only affect solid tumor patients but also limit its application in curing other diseases. This review explores the mechanisms underlying sorafenib-induced cardiovascular adverse effects, including endothelial dysfunction, mitochondrial dysfunction, endoplasmic reticulum stress, dysregulated autophagy, and ferroptosis. It also discusses potential treatment strategies, such as antioxidants and renin-angiotensin system inhibitors, and highlights the association between sorafenib-induced hypertension and treatment efficacy in cancer patients. Furthermore, emerging research suggests a link between sorafenib-induced glycolysis, drug resistance, and cardiovascular toxicity, necessitating further investigation. Overall, understanding these mechanisms is crucial for optimizing sorafenib therapy and minimizing cardiovascular risks in cancer patients.

A study integrated metabolomics and network pharmacology to investigate the effects of Shicao in alleviating acute liver injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Shicao is the aerial part of Achillea alpina L., a common herb found mainly in Europe, Asia, and North America. Traditional Chinese medicine has a history of thousands of years and is widely used to treat various diseases. AIM OF STUDY: To explore the hepatoprotective effects of Shicao on CCl4-induced acute liver injury. METHODS: A rat model of acute liver injury was established and liver function indices were assessed to evaluate the protective effect of Shicao on the liver. Untargeted metabolomics of the serum and liver tissues was conducted using UPLC-Q-TOF/MS to identify differential metabolites related to acute liver injury. A network of metabolite-reaction-enzyme-gene constituents was constructed using network pharmacology. Hub targets and key components of the effect of Shicao on acute liver injury were screened from the network. RESULTS: Compared to the model group, Shicao improved the degree of liver damage through the assessment of the liver index, ALT and AST levels, and hepatic pathology slices, demonstrating its hepatoprotective effect against acute liver injury in rats. 10 and 38 differential metabolites involved in acute liver injury were identified in serum and liver tissues, respectively. Most of these were regulated or restored following treatment with Shicao, which mainly consisted of bile acids, lipids, and nucleotides such as taurocholic acid, LysoPC (17:0), and adenosine diphosphate ribose. Through the network of metabolite-reaction-enzyme-gene-constituents, 10 key components and 5 hub genes, along with 7 crucial differential metabolites, were mainly involved in glycerophospholipid metabolism, purine metabolism, biosynthesis of unsaturated fatty acids, and primary bile acid biosynthesis, which may play important roles in the prevention of acute liver injury by Shicao. CONCLUSION: This study revealed that Shicao had protective effects against CCl4-induced liver injury in rats. It was speculated that the ingredients of Shicao might be closely related to the hub targets, thereby regulating the levels of key metabolites, affecting inflammatory response and oxidative stress and attenuate the liver injury consequently. This study provides a basis for further investigation of its therapeutic potential and the mechanism of action.

Substance basis and pharmacological mechanism of heat-clearing herbs in the treatment of ischaemic encephalopathy: a systematic review and network pharmacology.

BACKGROUND AND OBJECTIVE: Ischaemic encephalopathy is a common cerebrovascular disease caused by insufficient blood supply to the cerebral vessels. The ischaemic encephalopathy is closely associated with the development of many chronic diseases such as obesity, hypertension and diabetes. Neurotrophic therapy has become the main therapeutic strategy for ischaemic encephalopathy. However, neurotrophic drugs only slightly recover the neurological function of patients, and their long-term efficacy is uncertain. Previous reports revealed that the active ingredients of natural medicines play important roles in the treatment of cerebral ischemia. In this study, we reviewed clearing herbs with anti-ischaemic encephalopathy functions using the data from quantitative statistical and network pharmacological exploration methods. We also discussed the different bioactive components and pharmacological effects of these herbs. METHODS: First, we collected Chinese herbal prescriptions against ischaemic encephalopathy in four databases. Then, we statistically analysed the frequency of application of heat-clearing herbs to obtain the commonly used heat-clearing herbs against ischaemic encephalopathy, and classified them according to their efficacy according to the statistical results, to summarize the mechanism of anti-ischaemic effects of different bioactive components; Second, the network database was used to obtain the above components of heat-clearing Chinese medicines and their corresponding targets of action, disease targets of ischaemic stroke; Venny 2.1.0 was used to obtain component-disease target intersections; Cytoscape was used to construct the 'Drug-Active Ingredient-Target Network Graph '; DAVID was used for GO and KEGG enrichment analysis. RESULTS: Literature and database screening involved 149 prescriptions, with a total of 269 flavours of Chinese medicines and 20 flavours of single-flavour heat-clearing Chinese medicines; The top nine in terms of frequency of use were Radix Paeoniae Rubra、Rehmanniae Radix Praeparata、Figwort Root、Cortex Moutan、Scutellariae Radix、Coptidis Rhizoma、Gardeniae Fructus、Cassiae Semen、Lonicerae Japonicae Flos. The common components obtained from network pharmacology were beta-sitosterol, quercetin, and stigmasterol, which mainly act on key targets such as RELA, AKT1, JUN, PRKACA, PTGS2, RAF1 and CHUK; and their active ingredients are mainly involved in signalling pathways such as Calcium, PI3K-Ak, MAPK, cAMP, IL-17, HIF-1, TNF, T-cell receptor, NF-kappa B and JAK-STAT. CONCLUSIONS: Heat-clearing herbs are useful and promising for the protection against and prevention of ischemic encephalopathy. The results of the network pharmacological studies are similar to the mechanisms of anti-ischemic encephalopathy of the active ingredients of the purgative herbs we have listed; Thin either directly protects cerebrovascular tissues by improving vascular permeability and reducing the area of infarcted tissues, or produces protective effects through molecular signaling pathways. It can be seen that the components of heat-clearing Chinese medicines can exert cerebroprotective effects through multiple pathways, which provides us with a reference for further development and study of heat-clearing Chinese medicines in the treatment of ischemic cerebrovascular diseases.

Effects of restoration years on soil nitrogen and phosphorus in inland salt marshes.

Inland salt marsh wetlands have very important ecological functions in semi-arid areas. However, degradation and soil desertification have impacted these areas, making it necessary to study the impact of wetland restoration years on the soil quality of salt marsh wetland. We used remote sensing methods, field surveys, and inquiries to examine the seasonal profile effects of two-, four-, and six-year restoration periods on total nitrogen (TN), total phosphorus (TP) and the ratio of nitrogen to phosphorus (N:P) in P. australis and S. triqueter wetland natural states. Our results showed that soil TN in P. australis wetland in restored conditions was higher than that in natural conditions. The average soil TP of the S. triqueter wetlands at 0-10 cm, 10-20 cm, 20-30 cm, and 30-40 cm layers was 0.36 g/kg, 0.31 g/kg, 0.21 g/kg, and 0.17 g/kg s in September, respectively. The soil TP of the S. triqueter wetland increased slightly over the entire growing season. The restoration years had a great influence on the soil TP of the S. triqueter wetland from May to July. The soil TN in the P. australis wetland was almost restored to its natural condition in each layer during the six-year restoration period. The soil TP of the S. triqueter wetland was higher in the restored two-year period and showed a decreasing trend with an increased soil depth. Our conclusions can significantly guide the restoration of inland salt marsh wetlands.

Astragaloside IV-mediated inhibition of oxidative stress by upregulation of ghrelin in type 2 diabetes-induced cognitive impairment.

This study is to observe the upregulation effect of astragaloside IV on ghrelin in diabetic cognitive impairment (DCI) rats and to investigate the pathway in prevention and treatment by reducing oxidative stress. The DCI model was induced with streptozotocin (STZ) in conjunction with a high-fat and high-sugar diet and divided into three groups: model, low-dose (40 mg/kg), and high-dose (80 mg/kg) astragaloside IV. After 30 days of gavage, the learning and memory abilities of rats, as well as their body weight and blood glucose levels, were tested using the Morris water maze and then detection of insulin resistance, SOD activity, and serum MDA levels. The whole brain of rats was sampled for hematoxylin-eosin and Nissl staining to observe pathological changes in the hippocampal CA1 region. Immunohistochemistry was used to detect ghrelin expression in the hippocampal CA1 region. A Western blot was used to determine changes in GHS-R1α/AMPK/PGC-1α/UCP2. RT-qPCR was used to determine the levels of ghrelin mRNA. Astragaloside IV reduced nerve damage, increased superoxide dismutase (SOD) activity, decreased MDA levels, and improved insulin resistance. Ghrelin levels and expression increased in serum and hippocampal tissues, and ghrelin mRNA levels increased in rat stomach tissues. According to Western blot, it increased the expression of the ghrelin receptor GHS-R1α and upregulated the mitochondrial function associated-protein AMPK-PGC-1α-UCP2. Astragaloside IV increases ghrelin expression in the brain to reduce oxidative stress and delay diabetes-induced cognitive impairment. It may be related to the promotion of ghrelin mRNA levels.

Integrating Network Pharmacology and Experimental Verification to Investigate the Mechanisms of Shuangshi Tonglin Capsule to Treat Chronic Prostatitis.

BACKGROUND AND OBJECTIVE: Chronic prostatitis (CP) is one of the most common diseases in young and middle-aged men but lacks effective treatment. Shuangshi Tonglin Capsule (SSTLC) is a clinical drug for the treatment of chronic prostatitis. However, the underlying molecular mechanisms of SSTLC in treating CP are still unclear. In this study, we researched the underlying mechanisms of SSTLC in treating chronic prostatitis. METHODS: The ingredients of SSTLC were received from the TCMSP and BATMAN databases, and the CP targets were collected based on GeneCards and OMIM. Then, the PPI network and the "drug-ingredient-target" network map were constructed. GO and KEGG enrichment analyses by using DAVID. Molecular docking was performed by using AutoDock 4.2 and PyMol. And using animal experiments to verify the potential effect of SSTLC in CP. RESULTS: SSTLC contained 10 herbs, 158 chemical ingredients and 277 targets, 2002, diseaserelated targets were obtained. Network analysis outcomes indicated that VEGFA, TNF, MAPK1, EGFR, and MAPK8 are the key targets of SSTLC in treating chronic prostatitis. Furthermore, molecular docking revealed that quercetin, luteolin, and kaempferol exhibited a strong binding effect. Animal experimental indicated that SSTLC can reduce the pathological damage to prostate tissue. And, we found that high-dose SSTLC significantly reduced the level of TNF-α and downregulated the expression of EGFR, p-p38 and p-ERK1/2 (P<0.05). CONCLUSION: This study determined the pharmacological effects of SSTLC and the potential mechanism of action on SSTLC to treat CP, it provides a new idea for traditional Chinese medicine to treat chronic prostatitis.

Retraction notice to "Neuroprotective effect of Liuwei Dihuang decoction on cognition deficits of diabetic encephalopathy in streptozotocin-induced diabetic rat" [J. Ethnopharmacol. 150 (2013) 371-381].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. The authors have plagiarized/duplicated part of a paper that appeared in Neurosci Lett, 549 (2013) 63-68, (https://doi.org/10.1016/j.neulet.2013.06.002). Several images in the Journal of Ethnopharmacology paper; 3A, 3B, 4A, 4B correspond to figures; 2A, 2B, 3A and 3B respectively as published in Neuroscience Letters. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

Total flavonoids of sea buckthorn (Hippophae rhamnoides L.) improve MC903-induced atopic dermatitis-like lesions.

ETHNOPHARMACOLOGICAL RELEVANCE: Sea buckthorn (Hippophae rhamnoides L.) is popularly used as a herbal medicine and food additive in the world. Total flavonoids of Hippophae rhamnoides (TFH) are reported to have anti-inflammatory and immunomodulatory activities. AIM: The effects of TFH on atopic dermatitis (AD)-like lesions induced by MC903 in mice was elucidated in the study. METHODS: To induce AD-like lesions, MC903 was adopted to apply repeatedly on the left ear in C57BL/6 mice. After induction of AD-like lesions, 0.5% and 1% TFH cream was applied topically on ears of mice once a day for 8 days. The degree of skin lesions was evaluated by macroscopical and histological methods. Expressions of filaggrin (FLG) was evaluated by Western blotting. Real-time polymerase chain reaction (qPCR) was adopted to detect the mRNA expression of thymic stromal lymphopoietin (TSLP), interferon (IFN)-γ, interleukin (IL-4), tumor necrosis factor (TNF)-α in skin lesions. In vitro, Cytokine Antibody Arrays were performed to measure production of cytokines in IFN-γ/TNF-α-treated HaCaT cells, Western blotting was employed to detect the expressions of p-NF-κB, p-ERK and p-P38. RESULTS: Topical application of TFH significantly improved the severity of dermatitis by inhibiting the infiltration of mast cell, increasing expression of FLG, decreasing the expressions of TNF-α, IL-4, IFN-γ and TSLP in skin lesions. TFH decreased the levels of IL-1α, IL-1ß, IL-6, monocyte chemoattractant protein (MCP)-1, MCP-3, macrophage-derived chemokine (MDC), platelet-derived growth factor (PDGF)-BB, thymus and activation regulated chemokine (TARC) in the supernatants of the HaCaT cells treated by IFN-γ/TNF-α. Furthermore, expressions of p-NF-κB, p-ERK and p-P38 were also decreased by TFH administration with dose dependent manner in HaCaT cells treated by IFN-γ/TNF-α. CONCLUSIONS: Topical application of TFH improved AD-like lesions in mice induced by MC903. Which exerted the effects of anti-inflammation and repairing skin barrier by regulating Th1/Th2 balance. This finding indicates that TFH is a novel potential agent for the external treatment of AD.

Integrating Network Pharmacology and Experimental Models to Investigate the Mechanism of Huanglian Jiedu Decoction on Inflammatory Injury Induced by Cerebral Ischemia.

Unlike single-target Western medicines, traditional Chinese medicines (TCMs) exhibit diverse curative effects against multiple diseases through their "multicomponent" and "multitarget" manifestations. However, the material basis of the major therapeutic diseases and TCM underlying molecular mechanisms remain to be challenged. In the current study, we applied, for the first time, an integrated strategy that combines network pharmacology and experimental evaluation and explored and demonstrated the underlying possible mechanisms of a classic TCM formula, Huanglian Jiedu Decoction (HLJD), in the treatment of cerebral ischemia. First, the herb compound, protein compound, and GO-BP and KEGG pathways were constructed to predict the material basis of HLJD in the treatment of cerebral ischemia and explore the underlying molecular mechanisms. Network pharmacology analysis showed that HLJD treats cerebral ischemia mainly through its anti-inflammatory effect. We used molecular docking to verify that HLJD components have good binding activities to the arachidonic acid pathway enzymes, cyclooxylipase-2 (COX-2) and 5-lipoxygenase (5-LOX). Next, based on the prediction by the network pharmacology analysis, the rat model of middle cerebral artery occlusion (MCAO) was established to verify the efficacy of HLJD. The results showed that HLJD reduces the degree of brain injury in MCAO rats, probably by inhibiting the expression of the 5-LOX pathway and inflammatory response. In conclusion, our study demonstrates the effectiveness of integrating network pharmacology with an experimental study for material basis of the major therapeutic diseases and the underlying molecular mechanisms of TCM.

Biochemical basis of differential selenium tolerance in arugula (Eruca sativa Mill.) and lettuce (Lactuca sativa L.).

Selenium (Se) biofortification in crops provides a valuable strategy to enhance human Se intake. However, crops vary greatly with their capacity in tolerating and metabolizing/accumulating Se, and the basis underlying such variations remains to be fully understood. Here, we compared the effects of Se and its analog S treatments on plant growth and biochemical responses between a Se accumulator (arugula) and a non-accumulator (lettuce). Arugula exhibited an increased biomass production in comparison with untreated controls at a higher selenate concentration than lettuce (20 µM vs. 10 µM Na2SeO4), showing better tolerance to Se. Arugula accumulated 3-folds more Se and S than lettuce plants under the same treatments. However, the Se/S assimilation as assessed by ATP sulfurylase and O-acetylserine (thiol)lyase activities was comparable between arugula and lettuce plants. Approximately 4-fold higher levels of Se in proteins under the same doses of Se treatments were observed in arugula than in lettuce, indicating that Se accumulators have better tolerance to selenoamino acids in proteins. Noticeably, arugula showed 6-fold higher ascorbate peroxidase activity and produced over 5-fold more glutathione and non-protein thiols than lettuce plants, which suggest critical roles of antioxidants in Se tolerance. Taken together, our results show that the elevated Se tolerance of arugula compared to lettuce is most likely due to an efficient antioxidant defense system. This study provides further insights into our understanding of the difference in tolerating and metabolizing/accumulating Se between Se accumulators and non-accumulators.

Ameliorative effects of sea buckthorn oil on DNCB induced atopic dermatitis model mice via regulation the balance of Th1/Th2.

BACKGROUND: Atopic dermatitis (AD) is a worldwide chronic skin disease which burden public health. Sea buckthorn (SBT) (Hippophae rhamnoides L., Elaeagnaceae) oil, as a traditional herbal medicine, has been used for disease treatment for many years. The effects of SBT oil on AD mouse model induced by repeated administration of 2,4-dinitrochlorobenzene (DNCB) in BALB/c mice was evaluated in this study. METHODS: Mice were divided into four groups including the normal control group, AD model group, AD model group treated with SBT oil (5 ml/kg) and AD model group treated with SBT oil (10 ml/kg). Same volume at different concentrations of SBT oil was applied daily on the latter two groups by gavage for 15 days following AD model induction. The function of skin barrier and the production of IL-4, IFN-γ, TNF-α and TSLP were examined after animal sacrifice. The migration and mature of langerhans cell (LCs) in lymph node was further assessed by flow cytometry. RESULTS: SBT oil alleviated dermatitis scores, decreased ear thickness, prevented infiltration of mast cell, reduced lymph node weight and depressed activity of Th2 cells. SBT oil also reduced the expression of IL-4, IFN-γ, TNF-α and TSLP in ear tissue, IgE level in serum and mRNA relative expression of IL-4, IFN-γ, TNF-α in lymph node. Moreover, SBT oil inhibited the migration of LCs cells from local lesions to lymph node and it's mature in lymph node. CONCLUSIONS: These results suggest SBT oil had a beneficial effect either systemic or regional on DNCB-induced AD mice via maintain the balance of Th1/Th2 and may be a potential complementary candidate for AD treatment.

Efficacy of traditional Chinese Medicine combined with chemotherapy in patients with non-small cell lung cancer (NSCLC): a meta-analysis of randomized clinical trials.

BACKGROUND: This meta-analysis systematically evaluated the efficacy of Traditional Chinese Medicine (TCM) combined with chemotherapy and provided evidence-based evidence for the treatment of non-small cell lung cancer. METHODS: Biomedical databases including China National Knowledge Infrastructure (CNKI) database, Wanfang Database, PubMed, and Cochrane Library were searched from January 2005 to October 2019 for the clinical literature on Chinese medicine for treating non-small cell lung cancer. All randomized controlled trials (RCTs) concerning the TCM combined with chemotherapy for non-small cell lung cancer were selected. The total effective rate of clinical efficacy, quality of life (QOL), Karnofsky Performance Status (KPS) score, adverse drug reactions (ADRs) were extracted and analyzed. Review Manager 5.3 software was used for heterogeneity testing and combined statistical analysis. RESULTS: A total of 20 RCTs were included, with a total sample of 1669 cases, including 845 in the experimental group (TCM combined with chemotherapy) and 824 in the control group (chemotherapy alone). Compared with the control group, the experimental group significantly improved patients' QOL [OR = 2.79, 95% CI (1.87, 4.16), P < 0.00001], improved clinical efficacy [OR = 2.88, 95% CI (2.32, 3.58), P < 0.00001], increased KPS score [OR = 2.88, 95% CI (1.79, 4.62), P < 0.00001], and reduced the incidence of leukopenia [OR = 0.21, 95% CI (0.12, 0.37), P < 0.0001], thrombocytopenia [OR = 0.23, 95% CI (0.13, 0.40), P < 0.00001], hemoglobin reduction [OR = 0.17, 95% CI (0.10, 0.30), P < 0.00001], myelosuppression [OR = 0.24, 95% CI (0.10, 0.58), P < 0.001], nausea and vomiting [OR = 0.16, 95% CI (0.11, 0.22), P < 0.00001], diarrhea [OR = 0.21, 95% CI (0.12, 0.37), P < 0.00001], liver damage [OR = 0.17, 95% CI (0.10, 0.27), P < 0.00001], and kidney damage [OR = 0.30, 95% CI (0.10, 0.90), P = 0.03]. CONCLUSION: TCM combined with chemotherapy can improve clinical efficacy and KPS score, as well as improve patients' QOL and reduce ADRs caused by chemotherapy drugs.

Clinical efficacy and safety of Danhong injection for the treatment of chronic heart failure: A protocol for systematic review.

BACKGROUND: Danhong injection (DHI) has been widely in the treatment of chronic heart failure (CHF) in China; however, there is not enough clinical evidence DHI for treating CHF. METHODS: Two researchers will search literatures of DHI for CHF in databases. Extracted data are analyzed with Review Manager 5.3 software. The selected studies should be conducted quality evaluation, forest plots and funnel plots will be run by RevMan5.3. RESULTS: This systematic review validates the clinical efficacy and safety of DHI in the treatment of CHF through the analysis of New York Heart Association functional classification, left ventricular ejection fraction, left ventricular end-diastolic dimension, cardiac output, brain natriuretic peptide, adverse events. CONCLUSIONS: This systematic review will be provided a rational clinical evidence to evaluate the effectiveness and safety of DHI for the treatment of CHF. REGISTRATION NUMBER: PROSPERO CRD42019144686.

Clinical efficacy and safety of Shenqi Fuzheng injection for the treatment of chronic heart failure: Protocol for a meta-analysis and systematic review.

BACKGROUND: Chronic heart failure (CHF) is one of the most serious cardiovascular diseases. Shenqi Fuzheng injection (SQFZI), as a Chinese herbal injection, is usually used for the treatment of CHF. However, the clinical evidence of SQFZI for the treatment of CHF is unclear. METHODS: Two researchers will dependently search literatures of SQFZI for CHF from Chinese National Knowledge Infrastructure database, VIP database, Chinese Biological and Medicine database, Wangfang database, MEDLINE, EMBASE, Cochrane Library and Web of Science. These inclusive data of included studies will be conducted by RevMan 5.3 software. RESULTS: This meta-analysis and systematic review will provide a series of outcome measures to verify clinical efficacy and safety of SQFZI for treating CHF, including New York Heart Association (NYHA) function classification, left ventricular ejection fraction, left ventricular end-diastolic dimension, cardiac output, stroke volume, brain natriuretic peptide, N-terminal pro-brain natriuretic peptide, and adverse events. CONCLUSIONS: This meta-analysis and systematic review will provide up-to-date clinical evidence to assess SQFZI treatment efficacy for CHF patients.

Compound danshen dripping pills combined with trimetazidine in treating unstable angina pectoris: Protocol for a systematic review of randomized controlled trials.

BACKGROUND: Compound danshen dripping pills (CDDP) and trimetazidine (TMZ) are commonly used in the treatment of unstable angina pectoris (UAP). Currently, the combination of CDDP and TMZ has been widely used for UAP. However, the clinical evidence CDDP combined with TMZ for treating UAP is not sufficient. METHODS: We searched for randomized controlled trials testing CDDP combined with TMZ for the treatment of UAP in Chinese National Knowledge Infrastructure database, VIP database, Chinese Biological and Medicine database, Wangfang database, MEDLINE, EMBASE, Cochrane Library, and Web of Science. Extracted data are analyzed using Review Manager 5.3 software. The quality evaluation, forest plots and funnel plots will be conducted by RevMan5.3 software. Moreover, subgroup analysis and sensitivity analysis will also be completed by RevMan5.3. RESULTS: This systematic review will provide powerful clinical evidence of combination CDDP and TMZ for treating UAP. CONCLUSIONS: This systematic review will be provided up-to-date clinical evidence to evaluate the effectiveness and safety of CDDP combined with TMZ for the treatment of parents with UAP.Registration Number: PROSPERO CRD42019143100.

Research on the pharmacodynamics and mechanism of Fraxini Cortex on hyperuricemia based on the regulation of URAT1 and GLUT9.

Fraxini Cortex (also known as Qinpi, QP) has been used for the treatment of hyperuricemia with a significant difference on efficacy of QP from different regions. However, it`s still unknown whether proportion of components is the key and why same kind of herbs have different therapeutic effects. In this study, different sources of QP were collected from Shaanxi Qinpi extracts (SQPE), Henan Qinpi extracts (HQPE), Hebei Qinpi extracts (GQPE) provinces in China. Rat model of hyperuricemia with hypoxanthine combined with potassium oxonate were established to determine the levels of blood urea nitrogen (BUN), serum uric acid (SUA), urine uric acid (UUA) and creatinine (Cr). Hematoxylin-eosin staining (H&E) and Periodic Acid-Schiff staining (PAS) were performed for renal pathology while Western blot analysis and real-time PCR analysis for proteins and mRNA expression levels. High-performance liquid chromatograph (HPLC) was used for components and composition analysis. Our results demonstrated that QPE from different regions could alleviate hyperuricemia via increasing significantly the SCr and BUN levels whereas decreasing markedly UCr, SUA and UUA levels. Additionally, QPE could also improve the pathological changes of the kidneys. The protein and mRNA levels of urate reabsorption transporter 1 (URAT1) and glucose transporter 9 (GLUT9) were down-regulated by QPE treatment. SQPE hold a better activity on improving hyperuricemia and regulating URAT1 and GLUT9. HPLC analysis showed that the proportion of four components aesculin, aesculetin, fraxin, fraxetin were 9.002: 0.350: 8.980: 0.154 (SQPE); 0.526: 0.164: 7.938: 0.102 (HQPE); 12.022: 1.65: 0.878: 1.064 (GQPE). These data indicate that this proportion of effective components may be an important factor for efficacy of QP and had implications for the treatment of hyperuricemia.

Ginseng improves cognitive deficit via the RAGE/NF-κB pathway in advanced glycation end product-induced rats.

BACKGROUND: Ginseng, the root of Panax ginseng (PG), is used widely as a herbal medicine to prevent and treat various diseases. Panax ginseng has pharmacological effects on neurodegenerative diseases such as Alzheimer's disease (AD). The present study evaluated the neuroprotective effects of PG and its possible neuroprotective mechanisms in advanced glycation end product (AGE)-induced AD in a rat model. METHODS: Advanced glycation end products were injected bilaterally into the CA3 region of the rats' brains. The Morris water maze test and step-down type passive avoidance test were performed to evaluate their memory and cognitive abilities. The oxidation indexes in the hippocampus were detected. Immunohistochemistry was conducted to visualize the receptors for advanced glycation end products (RAGEs) and nuclear factor-kappa-light-chain-enhancer of activated B cell (NF-κB). RESULTS: Behavioral results showed that PG (1 g/kg, 0.5 g/kg, and 0.25 g/kg) significantly shortened the escape latency, remarkably increased the number of crossing times, significantly decreased the number of errors, and prolonged the latency in rats with AGE-induced AD. Panax ginseng also significantly reduced the malondialdehyde level, increased the glutathione content, and increased superoxide dismutase activity in the hippocampus. Panax ginseng significantly decreased the expression of RAGE and NF-κB. The blockade of anti-RAGE antibody could significantly reduce AGE-induced impairments and regulate these expressions. CONCLUSION: Our results demonstrated that PG significantly inhibits AGE-induced memory impairment and attenuates Alzheimer-like pathophysiological changes. These neuroprotective effects of PG may be associated with the RAGE/NF-κB pathway. Our results provided the experimental basis for applying PG in preventing and treating AD.

Blockade of emodin on amyloid-ß 25-35-induced neurotoxicity in AßPP/PS1 mice and PC12 cells through activation of the class III phosphatidylinositol 3-kinase/Beclin-1/B-cell lymphoma 2 pathway.

Autophagy plays an important role in the pathogenesis of Alzheimer's disease. In the present study, the blockade mechanism of emodin on amyloid-ß 25-35-induced neurotoxicity was explored. Cell viability of PC12 cells was evaluated by the MTT assay and neuro damage by the lactate dehydrogenase leakage assay. Gene silencing by small interfering RNA, cDNA constructs and transfection, as well as Western blot were performed to assess protein expression levels. AßPP/PS1 mice were administered orally with emodin (50 mg/kg/day), and LC3-II positive cells in their brain cortex sections were detected by immunohistochemical staining. Emodin could significantly inhibit the LC3-I/LC3-II conversion ratio and cell viability while decreasing the lactate dehydrogenase level in AßPP/PS1 mice and PC12 cells. LC3II positive cells in the cortex were decreased significantly by the treatment with both emodin and 3-methyladenine. Furthermore, emodin and 3-methyladenine could increase B-cell lymphoma 2 while decreasing Beclin-1 and hVps34 expressions, which were induced by amyloid-ß 25-35. Small interfering gene silencing Beclin-1 and B-cell lymphoma 2 confirmed this signaling pathway. We also found that the phosphatidylinositol 3-kinase inhibitor LY294002 could block LC3-I/LC3-II conversion and increase B-cell lymphoma 2 while decreasing hVps34 and Beclin-1 expressions. The results suggest that the blockade of emodin on amyloid-ß 25-35-induced autophagy may occur via the activation of the class III phosphatidylinositol 3-kinase/Beclin-1/B-cell lymphoma 2 pathway. Our results provide confirmatory evidence for the application of emodin in the prevention and treatment of Alzheimer's disease.

Tectorigenin inhibits the inflammation of LPS-induced acute lung injury in mice.

AIM: In a previous study, the anti-inflammatory effects of tectorigenin were disclosed. In this study, the anti-inflammatory effects of tectorigenin on acute lung injury using a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model were investigated METHOD: The cell-count in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by the wet/dry weight (W/D) ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity was assayed using SOD and MPO kits, respectively. The levels of inflammatory mediators, including tumor necrosis factor-α (TNF-α), IL-1ß, and IL-6 were assayed using an enzyme-linked immunosorbent assay method. Pathological changes of lung tissues were observed through HE staining. The inflammatory signal pathway related protein nuclear factor NF-κB p65 mRNA expression was measured by real-time PCR, and the protein level of NF-κB p65 was measured using Western blotting analysis. RESULTS: The data showed that treatment with the tectorigenin markedly attenuated the inflammatory cell numbers in the BALF, decreased nuclear factor NF-κB p65 mRNA level and protein level in the lungs, and improved SOD activity and inhibited MPO activity. Histological studies showed that tectorigenin substantially inhibited LPS-induced neutrophils in lung tissue compared with the model group. CONCLUSION: The results indicated that tectorigenin had a protective effect on LPS-induced ALI in mice.

Ginsenoside Rg5 improves cognitive dysfunction and beta-amyloid deposition in STZ-induced memory impaired rats via attenuating neuroinflammatory responses.

Neuroinflammatory responses play a crucial role in the pathogenesis of Alzheimer's disease (AD). Ginsenoside Rg5 (Rg5), an abundant natural compound in Panax ginseng, has been found to be beneficial in treating AD. In the present study, we demonstrated that Rg5 improved cognitive dysfunction and attenuated neuroinflammatory responses in streptozotocin (STZ)-induced memory impaired rats. Cognitive deficits were ameliorated with Rg5 (5, 10 and 20mg/kg) treatment in a dose-dependent manner together with decreased levels of inflammatory cytokines TNF-α and IL-1ß (P<0.05) in brains of STZ rats. Acetylcholinesterase (AChE) activity was also significantly reduced by Rg5 whereas choline acetyltransferase (ChAT) activity was remarkably increased in the cortex and hippocampus of STZ-induced AD rats (P<0.05). In addition, Congo red and immunohistochemistry staining results showed that Rg5 alleviated Aß deposition but enhanced the expressions of insulin-like growth factors 1 (IGF-1) and brain derived neurophic factor (BDNF) in the hippocampus and cerebral cortex (P<0.05). Western blot analysis also demonstrated that Rg5 increased remarkably BDNF and IGF-1 expressions whereas decreased significantly Aß deposits (P<0.05). Furthermore, it was observed that the expressions of COX-2 and iNOS were significantly up-regulated in STZ-induced AD rats and down-regulated strongly (P<0.05) by Rg5 compared with control rats. These data demonstrated that STZ-induced learning and memory impairments in rats could be improved by Rg5, which was associated with attenuating neuroinflammatory responses. Our findings suggested that Rg5 could be a beneficial agent for the treatment of AD.