Efficacy and safety of apatinib versus sorafenib/placebo in first-line treatment for intermediate and advanced primary liver cancer: A systematic review and meta-analysis.

Background: Apatinib is a novel tyrosine kinase inhibitor used in the treatment of advanced hepatocellular carcinoma (HCC). For decades, sorafenib has been a classic first-line treatment option for patients with HCC. This meta-analysis aimed to assess the efficacy and safety of apatinib versus sorafenib/placebo as first-line treatment for intermediate and advanced primary liver cancer (PLC). Methods: A literature search was performed via PubMed, Web of Science, CENTRAL, Embase, CNKI, VIP, and CBM. Data extraction from databases of other languages is not restricted. The Cochrane risk of bias tool, modified Jadad scale, Newcastle-Ottawa scale (NOS), and non-randomized studies of interventions (ROBINS-I) tool were employed to evaluate methodological qualities in original studies. Influence analysis was applied to assess the reliability of pooled results. Publication bias was evaluated using the funnel plot with Begg's test and Egger's test. Results: Seven studies were included in the systematic review and meta-analysis. Four randomized controlled trials (RCTs) and one clinical controlled trial (CCT) were used for comparing apatinib with placebo, and two retrospective clinical studies (RCSs) were used for comparing apatinib with sorafenib. Apatinib led to higher overall effects in objective response rate (ORR), disease control rate (DCR), and mean survival time (MST) over placebo (RR = 2.03, 95% CI = 1.46-2.81, p < 0.0001, I2 = 0%; RR = 1.17, 95% CI = 1.04-1.33, p = 0.009, I2 = 45.8%; SMD = 2.63; 95% CI = 1.47-3.78, p < 0.0001, I2 = 92.7%, respectively). Compared to sorafenib, apatinib showed no superiority in ORR and DCR but was inferior in the 6-month and 1-year survival rate (RR = 1.99, 95% CI = 0.85-4.65, p = 0.111, I2 = 68.3%; RR = 1.04, 95% CI = 0.73-1.47, p = 0.840, I2 = 0.0%; RR = 0.63, 95% CI = 0.42-0.97, p = 0.036, I2 = 0.0%; RR = 0.47, 95% CI = 0.29-0.79, p < 0.0001, I2 = 0.0%, respectively). Apatinib had similar adverse effects over placebo but possessed a greater incidence rate of proteinuria and hypertension over sorafenib. Conclusion: In the first-line setting, apatinib might be an alternative treatment approach for patients with intermediate and advanced PLC. Sorafenib alone showed a better survival rate within 1 year and a lower incidence rate in hypertension and proteinuria than apatinib monotherapy.

Antibacterial activity and underlying mechanism of Meconopsis quintuplinervia Regel extract against the acne-causing bacteria Propionibacterium acnes and Staphylococcus aureus.

The aim of this study was to evaluate the antibacterial activity and underlying mechanism of ethanol extracts of Meconopsis quintuplinervia Regel (EMQ) against the acne-causing bacteria Propionibacterium acnes and Staphylococcus aureus. The study results indicated that EMQ was an effective antibacterial agent against P. acnes and S. aureus, with a DIZ of 14.5 and 13.2mm, MIC of 12.5 and 12.5mg/mL and MBC of 100 and 50mg/mL, respectively. EMQ induced morphological changes to bacterial cells, as determined by electron microscopy. Leakage of alkaline phosphatase and nucleic acids confirmed that EMQ compromised the membrane integrity of bacterial cells. Furthermore, protein analysis revealed that EMQ hindered total protein expression and lowered adenosine triphosphatase activity, while crystal violet staining revealed suppressed biofilm production. Bacterial adhesion analysis demonstrated that EMQ lowered the adhesive capacity of bacterial cells. The main chemical components of EMQ, identified by LC-MS, seem to have important roles in the antimicrobial effects against P. acnes and S. aureus, suggesting EMQ is a promising therapeutic for acne treatment.

Ajania purpurea Extract Attenuates LPS-Induced Inflammation in RAW264.7 Cells and Peritonitis Mice.

Macrophages have important roles in the progression of inflammation. Ajania purpurea Shih. is a member of the Ajania Poljakor family that grows in Tibet (China). Extracts from plants in this genus have anti-bacterial and anti-inflammatory properties. However, there are few reports on the activity and mechanism of Ajania purpurea. Here, we confirmed the anti-inflammatory effect of Ajania purpurea Shih. ethanol extract (EAPS) by examining the levels of inflammatory factors in a mouse model of peritonitis and RAW264.7 cells. The main components of EAPS detected by LC-MS analysis included piperine and chlorogenic acid. In particular, in lipopolysaccharide (LPS)-induced RAW264.7 cells, EAPS inhibited the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-induced RAW264.7 cells, lowered the levels of nitric oxide (NO) and prostaglandin E2 (PGE2), as well as the release of inflammatory factors such as tumor necrosis factor-alpha (TNF-α) and pro-inflammatory cytokines such as interleukin (IL)-1ß and IL-6. In addition, Western blot analysis and immunofluorescence staining verified that EAPS inhibited the activity of the nuclear factor-kappaB (NF-κB) pathway by reducing the nuclear translocation of the p65 subunit. Furthermore, in a mouse model of peritonitis, EAPS inhibited the release of inflammatory factors, as well as the recruitment of immune cells including neutrophils and macrophages. These findings indicated that EAPS suppressed LPS-induced inflammation via inhibiting the NF-κB pathway in RAW264.7 cells and mice with peritonitis. Thus, EAPS may be a viable therapeutic method for the treatment of inflammation and related disorders.

Chinese Medicine Meets Conventional Medicine in Targeting COVID-19 Pathophysiology, Complications and Comorbidities.

OBJECTIVE: To investigate how the National Health Commission of China (NHCC)-recommended Chinese medicines (CMs) modulate the major maladjustments of coronavirus disease 2019 (COVID-19), particularly the clinically observed complications and comorbidities. METHODS: By focusing on the potent targets in common with the conventional medicines, we investigated the mechanisms of 11 NHCC-recommended CMs in the modulation of the major COVID-19 pathophysiology (hyperinflammations, viral replication), complications (pain, headache) and comorbidities (hypertension, obesity, diabetes). The constituent herbs of these CMs and their chemical ingredients were from the Traditional Chinese Medicine Information Database. The experimentally-determined targets and the activity values of the chemical ingredients of these CMs were from the Natural Product Activity and Species Source Database. The approved and clinical trial drugs against these targets were searched from the Therapeutic Target Database and DrugBank Database. Pathways of the targets was obtained from Kyoto Encyclopedia of Genes and Genomes and additional literature search. RESULTS: Overall, 9 CMs modulated 6 targets discovered by the COVID-19 target discovery studies, 8 and 11 CMs modulated 8 and 6 targets of the approved or clinical trial drugs for the treatment of the major COVID-19 complications and comorbidities, respectively. CONCLUSION: The coordinated actions of each NHCC-recommended CM against a few targets of the major COVID-19 pathophysiology, complications and comorbidities, partly have common mechanisms with the conventional medicines.

Alkaloids from Dendrobium and their biosynthetic pathway, biological activity and total synthesis.

BACKGROUND: Dendrobium Sw. has been used for thousands of years in China as a precious traditional Chinese medicine. It is derived from stems of various Dendrobium plants and has the functions of nourishing Yin and clearing heat, activating water and nourishing the stomach, moistening the lung and relieving cough. Modern phytochemical studies show that the main components of Dendrobium include alkaloids, polysaccharides, terpenoids, diphenylbenzene, and phenanthrene. Alkaloids are natural products with obvious biological activity and are important effective components of the medicinal activity or toxicity of plants. At present, dozens of alkaloids with various structures have been isolated from Dendrobium plants, and the alkaloid contents in Dendrobium plants of different species are quite different. From the perspective of food safety, the type, molecular structure, content and potential physiological activity or toxicity of alkaloids are important bases for evaluating the safety of edible plants. Studies have shown that the alkaloids isolated from Dendrobium have neuroprotective, anti-inflammatory and antitumor activities, showing that these alkaloids with potential medicinal activity are important sources of lead compounds in innovative drug development. PURPOSE: To summarize the research progress on alkaloids in Dendrobium and provide a reference for research on the food safety and medicinal development of Dendrobium. METHOD: Information about alkaloids from Dendrobium was collected from the scientific databases Web of Science, PubChem and PubMed. We discuss the biosynthetic pathway, biological activities and total synthesis of alkaloids from Dendrobium from 1964 to 2020 and summarize the knowledge of alkaloids from Dendrobium, the biosynthetic pathway, biological activities and total synthesis. We chose publications on their chemistry, drug effects, pharmacology, metabolism and biosynthesis, physiology and toxicity. Alkaloids, Dendrobium, biosynthetic pathway and biological activities were used as keywords to extract the relevant literature. CONCLUSION: In this paper, the structural classification, biological activity, target and toxicology and synthesis of the alkaloids in Dendrobium were systematically reviewed, which will provide a reference for the safety, development and application of Dendrobium.

Hepatoprotective effect of Sophora moorcroftiana (Benth.) Benth.Ex baker seeds in vivo and in vitro.

The leguminosae of Sophora moorcroftiana (Benth.) Benth.ex Baker is a drought-resistant endemic Sophora shrub species from the Qinghai-Tibet Plateau, and its seeds have hepatoprotective effects. To study the effect of S. moorcroftiana seeds on liver injury and the molecular mechanism underlying the beneficial effects, liquid chromatography-mass spectrometry was used to detect the main active components in the ethanol extract of S. moorcroftiana seeds (SM). Male mice were divided into six groups (n = 8): normal control (NC), CCl4, SM (50, 100, 200 mg/kg), and dimethyl diphenyl bicarboxylate (150 mg/kg) groups. Mice were treated as indicated (once/day, orally) for 14 days, and CCl4 (2 mL/kg) was administered intraperitoneally. The serum and liver of mice were used for biochemical assays. To explore the underlying mechanism, HepG2 cells were treated with SM, stimulated with tert-butyl hydroperoxide (t-BHP, 50 µM), and analyzed by Western blotting. The major active compounds of SM were alkaloids including 22 compounds. Serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) decreased in the SM (200 mg/kg) group. SM can activate the expression of pregnane X receptor (PXR) and downstream molecules cytochrome P4503A11 enzyme (CYP3A11), UDP glucuronosyltransferase 1 family polypeptide A 1 (UGT1A1), and inhibit the multidrug resistance protein 2 (MRP2). In addition, SM improved cell viability in t-BHP-induced HepG2 cells (64% to 83%) and decreased the activation of the mitogen-activated protein kinase (MAPK) pathway. The main compounds in SM were alkaloids. SM showed hepatoprotective effects possibly mediated by the suppression of oxidative stress through the MAPK pathway.

Taraxacum officinale Wigg. Attenuates Inflammatory Responses in Murine Microglia through the Nrf2/HO-1 and NF-κB Signaling Pathways.

As a long-established medicinal and edible homologous plant, Taraxacum officinale Wigg. is widely distributed in Asia, Europe, and other parts of the world. T. officinale is reported to exert a variety of biological and pharmacological activities, including anticancer, hepatoprotective, and anti-obesity effects. In this study, we evaluated the anti-inflammatory effects of ethanol extracts of T. officinale (A-TOW) by examining the suppression of proinflammatory mediators in LPS-stimulated BV2 and mouse hippocampus. Furthermore, A-TOW also inhibited the nuclear translocation of nuclear factor κB p65 caused by stimulation with LPS. In addition, A-TOW regulates heme oxygenase (HO)-1 expression through the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in BV2 cells. The effects of A-TOW on the over-expression of proinflammatory mediators were partially reversed by transfection of the cells with HO-1 siRNA. These findings suggest that the potent anti-inflammatory activity of T. officinale, possibly through the regulation of Nrf2/HO-1 and NF-κB signaling pathway.

Nepeta angustifolia C. Y. Wu improves renal injury in HFD/STZ-induced diabetic nephropathy and inhibits oxidative stress-induced apoptosis of mesangial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: As an important medicinal material constituting a variety of traditional Chinese medicine prescriptions, Nepeta angustifolia C. Y. Wu was used as a folk medicine to treat various vascular-related diseases including apoplexia, and cerebral haemorrhage in Tibet, China. Our previous studies have shown that this plant had a significant protective effect on vascular dysfunction of the intracerebral haemorrhage and diabetic rats. In present study, we aimed to investigate the protective effects and underlying mechanisms of Nepeta angustifolia on diabetic nephropathy (DN), a microvascular complication. AIM OF THE STUDY: This study is aim to evaluate the protective effect of ethanol extracts of N. angustifolia (NA) on DN, and explore mechanism of action to provide basis for its pharmacological action against DN. MATERIALS AND METHODS: High-fat diet and low-dose streptozotocin administration (HFD/STZ) induced diabetic rats were randomly divided into 5 groups (n = 8): the diabetic model group, metformin group, and three dose groups of NA (60 mg/kg, 120 mg/kg, 240 mg/kg). After administration of NA for 8 weeks, the blood, urine and renal tissue were collected for subsequent experiments. Biochemical markers (urine protein, Cr, BUN), oxidative stress makers (SOD, GSH-px and MDA) and pro-inflammatory mediators (TNF-α, IL-1ß, IL-6 and MCP-1) were evaluated by commercial kit and ELISA, respectively. The effect of NA on DN was further confirmed by evaluation of renal histopathology by using the H&E, PAS and Masson staining. The H2O2-induced HBZY-1 cells (rat glomerular mesangial cells) were also been used to evaluate the renal protective effect of NA (50 µg/mL, 100 µg/mL, 200 µg/mL). The oxidative stress makers were detected by commercial kit. The levels of apoptosis and related proteins (caspase 3, 9) were detected by TUNEL assay and western blot analysis, respectively. The depolarization of mitochondrial membrane potential was detected by JC-1 staining assay. RESULTS: The administration of NA is helpful to maintain near normal body weight, blood glucose, urine volume, urine protein, kidney index and serum levels of Cr and BUN. NA treatment significantly improve renal dysfunction by the down-regulation of renal oxidative stress and pro-inflammatory mediators in HFD/STZ induced diabetic rats. In vitro experiments, NA has a significant cellular protective effect in H2O2-induced HBZY-1 cells, as well as the regulation in increases of SOD level and the decreases of ROS and MDA levels. Furthermore, NA treatment can significantly inhibit H2O2 induced mesangial cells apoptosis by the increasing mitochondrial potential and suppressing caspases-madiated signaling pathway. CONCLUSIONS: NA has obvious improvement on renal dysfunction in HFD/STZ induced diabetic rats. NA can protect mesangial cells by inhibiting oxidative stress induced apoptosis, which may be related to its regulation of mitochondrial-caspase apoptosis pathway.

[Multi-component quantitative analysis combined with chromatographic fingerprint for quality assessment of Onosma hookeri].

A method for simultaneous determination of the shikonin, acetyl shikonin and ß, ß'-dimethylpropene shikonin in Onosma hookeri and the chromatographic fingerprint was estabished by HPLC-DAD on an Agilent Zorbax SB-column with a gradient elution of acetonitrile and water at 0.8 mL x min(-1), 30 degrees C. The quality assessment was conducted by comparing the content difference of three naphthoquinone constituents, in combination with chromatographic fingerprint analysis and systems cluster analysis among 7 batches of radix O. hookeri. The content of the three naphthoquinone constituents showed wide variations in 7 bathces. The similarity value of the fingerprints of sample 5, 6 and 7 was above 0.99, sample 2 and 3 above 0.97, sample 3 and 4 above 0.90, and other samples larger than 0.8, which was in concert with the content of three naphthoquinone constituents. The 7 samples were roughly divided into 4 categories. The results above indicated that the using of this medicine is complex and rather spotty. The established HPLC fingerprints and the quantitative analysis method can be used efficiently for quality assessment of O. hookeri.

[Normal light and fluorescence microscopy for authentication of Delphinii Brunoniani Herba of Tibet].

Dried herb of Delphinium brunonianum Royle (Ranunculaceae) has long been used under the herbal name "Xiaguobei" (Delphinii Brunoniani Herba) in traditional Tibetan medicine and prescribed for the treatment of influenza, itchy skin rash and snake bites. In order to find a useful and convenient method for the identification of microscopic features, the technique of fluorescence microscopy was applied to authenticate "Xiaguobei" of Tibet. The transverse sections of stem and leaf, as well as the powder of "Xiaguobei" were observed to seek for typical microscopic features by normal light and fluorescence microscopy. A style-like, single-cell glandular hair containing yellow secretions on the leaf, young stem and sepal of "Xiaguobei" was found. Under the fluorescence microscope, the xylem and pericycle fiber group emitted significant fluorescence. This work indicated that fluorescence microscopy could be an useful additional method for the authentication work. Without the traditional dyeing methods, the main microscopic features could be easily found by fluorescence microscopy. The results provided reliable references for the authentication of "Xiaguobei".