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ML385, a selective inhibitor of Nrf2, abolished the flagellin-mediated hepatoprotective effects in damaged livers and hepatocytes. Additionally, the flagellin-induced Nrf2 translocation was dependent upon the activation of TLR5-JNK/p38 pathways. These findings suggest that TLR5 signaling-induced Nrf2 activation, at least partially, contributed to the protection against APAP-induced ALI by flagellin treatment.As a typical persistent organic pollutant, decabromodiphenyl ether (BDE-209) is associated with various health risks, especially on immune system, which is sensitive to environmental pollutants. In addition, there is a problem of multi-index estimation and lack of comprehensive evaluation in immune toxicity study. In this study, the immunotoxicity of BDE-209 was systematically estimated from the aspects of immunopathology, humoral immunity, cellular immunity and non-specific immunity, etc., and integrated biomarker responses (IBR) combined with principal component analysis was applied to comprehensively evaluate the immunotoxicity of BDE-209 and its self-recovery after discontinuation. Results showed that BDE-209 exposure could cause immunotoxicity. CVT-313 molecular weight This response seems to depend on (1) atrophying immune organs (thymus and spleen), hepatomegaly accompanied by increasing aspartate aminotransferase and oxidative stress;(2) changing humoral (immunoglobulins) and cellular (lymphocyte proliferation and cytokine secretion) immunity indices; (3) altering related expressions of genes, and further leading to imbalance of Th1/Th2 (Th, helper T cell). Integrated biomarker responses (IBR) companied with principal component analysis selected five biomarkers (mRNA expression of GATA-3, malondialdehyde level in thymus, count of white blood cell, serum IgG and lipopolysaccharide-induced splenic lymphocyte proliferation) to clarify the immunotoxicity induced by BDE-209. Furthermore, IBR combined with factorial analysis revealed that the effect of BDE-209 could be dose-dependently reduced after withdrawal of BDE-209. Overall results suggested that BDE-209 has immunotoxicity on adult Balb/c mice, whereas this immunotoxicity could be reduced by the self-regulation of organisms to some extent.

Shengmai San (SMS) has been commonly used as a traditional Chinese medicine for the treatment of cardiovascular disorders, of which drug interactions need to be assessed for the safety concern. There is little evidence for the alterations of hepatic and intestinal drug-metabolizing enzymes after repeated SMS treatments to assess drug interactions.

The studies aim to illustrate the effects of repeated treatments with SMS on cytochrome P450s (CYPs), reduced nicotinamide adenine dinucleotide (phosphate)-quinone oxidoreductase (NQO), uridine diphosphate-glucuronosyltransferase (UGT), and glutathione S-transferase (GST) using in vivo rat model.

The SMS was prepared using Schisandrae Fructus, Ginseng Radix, and Ophiopogonis Radix (OR) (122). Chromatographic analyses of decoctions were performed using ultra-performance liquid chromatography (UPLC) and LC-mass spectrometry. Sprague-Dawley rats were orally treated with the SMS and its component herbal decoctions for 2 or 3 weeks. Hepatic and intestinal enzyme acCYP3A function. It suggested that the potential interactions of SMS with CYP 3A drug substrates should be noticed, especially the drugs whose bioavailability depends heavily on intestinal CYP3A.

The growing challenge to access conventional analgesics, contraindications, and adverse effects could have led individuals to use Schkuhria pinnata (Lam.) Kuntze ex Thell. (Compositae), as an alternative traditional therapeutic strategy for pain. However, evidence of its safety and efficacy is scarce.

This study evaluated the anti-nociceptive effect of the ethanol extract of the aerial parts of S. pinnata in mice.

The mice were randomly assigned to nine groups (1) vehicle; (2) acetylsalicylic acid (intraperitoneally 150mg/kg); (3) pentazocine (intramuscularly 1.0mg/kg); (4 a & b) orally 100mg/kg extract; (5 a & b) orally 200mg/kg extract; (6 a & b) orally 400mg/kg extract. We used an acetic acid-induced writhing model and a tail-flick test. The number of writhes and time taken for the tail to flick was recorded. A one-way analysis of variance followed by Tamhane T2 post hoc was used for multiple comparisons.

Compared to a vehicle (59.0±2.68), S. pinnata ethanol extract at a dose of 200 and 400mg/kg, p.o reduced writhes to 42.5±1.12 and 27.0±2.62, (p<0.05) respectively. Similarly, the pain threshold of mice increased dose-dependently; doses of 200 and 400mg/kg, increased time to 5.33±0.42 and 8.67±0.21min, (p<0.05) respectively. The extract had an EC50 of 348.8mg/kg and acute toxicity established an LD50 of 1224.8 (95% CI 952.2-1575.3).

S. pinnata ethanol extract had anti-nociceptive activity by central and peripheral mechanisms that could justify its traditional use in pain management. Further studies could now focus on identifying active fractions and pure isolated compounds responsible for anti-nociceptive activity.

S. pinnata ethanol extract had anti-nociceptive activity by central and peripheral mechanisms that could justify its traditional use in pain management. Further studies could now focus on identifying active fractions and pure isolated compounds responsible for anti-nociceptive activity.

25 flavors of the turquoise pill, a traditional Tibetan medicine for the treatment of various types of hepatitis, has not been investigated on its safety, especially the component mineral turquoise, which is believed to be essential but worried for its potential toxicity.

To explore the potential acute toxicity and function of 25 flavors of the turquoise pill and turquoise, the possible mechanism of the effects of turquoise and 25 flavors of the turquoise pill were systematically studied based on

H NMR metabolomics.

The rats were administered with turquoise and 25 flavors of the turquoise pill by gavage for 7 days, and samples of serum, liver, and kidney were collected. The potential toxicity and function of turquoise and 25 flavors of the turquoise pill on the liver and kidney of SD rats were evaluated by

H NMR metabonomics, histopathology, and biochemical indexes.

The results demonstrated that 25 flavors of the turquoise pill could scavenge free oxygen radicals, strengthen aerobic respiration and inhibit glycolysis in the liver. It did not cause oxidative stress in the kidney with no obvious damage. By modulation of branched-chain amino acids (BCAAs), 25 flavors of the turquoise pill can improve the utilization of glucose and promote aerobic respiration of the kidney.

Considering the high dosage and short duration used in this study relative to their typical clinical usage, administration of 25 flavors of the turquoise pill and its component mineral turquoise are safe to livers and kidneys.

Considering the high dosage and short duration used in this study relative to their typical clinical usage, administration of 25 flavors of the turquoise pill and its component mineral turquoise are safe to livers and kidneys.

Kaempferia galanga L. rhizome (KGR) is part of more than sixty-one Ayurvedic formulations and commonly known as 'Chandramula'. KGR is widely used in traditional Indian medicines to treat fever (jwar), rheumatism (Amavata), respiratory (Shwasa), hypertension (Vyanabala vaishamya) and cardiovascular disorders (Vyanavayu Dushtijanya Hrudrog). Although ethnomedicinal properties have extensively been demonstrated in traditional medicines of south-east countries i.e. China, India, Indonesia, and Malaysia, the chemico-biological validation are still lacking.

Chemico-biological standardization with respect to its vasorelaxation potential is the main objective of the present study. To investigate the vasorelaxation potential of key phytochemical of KGR, i.e., ethyl-p-methoxycinnamate (EPMC) and to study it's the mechanism of action.

A HPLC method was developed and validated for the quality assessment of KGR using its two major phytochemicals i.e. ethyl-p-methoxycinnamate (EPMC) and ethyl cinnamate (EC) in KGR. Tc BK

channel blocker (TEA, 1mM), the relaxation response to EPMC was also significantly blocked.

The first time this study demonstrated the chemical standardization of K. galanga rhizome and EPMC is responsible for its vasorelaxation potential as demonstrated by the endothelium-independent response mediated by Ca2+ dependent potassium channels.

The first time this study demonstrated the chemical standardization of K. galanga rhizome and EPMC is responsible for its vasorelaxation potential as demonstrated by the endothelium-independent response mediated by Ca2+ dependent potassium channels.

The genus Brugmansia belongs to the Solanaceae family and contains approximately 7-8 species distributed in America, Europe, Africa, and Asia. The genus Brugmansia plants are used in the traditional medicine of different parts of the world for the treatment of inflammations, rheumatic arthritis, wounds, skin infections, headache, asthma, colic, aches, and so on.

To the best of our knowledge, this is the first review study that focuses on the phytochemistry, pharmacology, toxicity, and traditional uses of Brugmansia species in order to understand the link between the traditional uses, phytochemistry, and modern therapeutic uses, and provide a scientific fundamental for further research in the phytochemical and pharmacological activities of their species.

The information reported in this study was retrieved from the scientific database such as ScienceDirect, PubMed, Springer, CNKI, Wiley, Google Scholar, and Baidu Scholar, up until May 2020. The key search word was "Brugmansia." Additionally, information r species have interesting chemical constituents with different biological activities. The traditional uses of some species from this genus have been estimated by pharmacological activities, such as the anti-inflammatory, antispasmodic, antiasthma, antinociceptive, anti-addictive, and antiprotozoal activity. However, the traditional uses of many species have not been confirmed, also the secondary metabolites of the many species have not yet been determined and have never been pharmacologically estimated. Considerably more research is needed to assert the ethnopharmacological uses, determine the chemical constituents, toxicity, and pharmacological activities of the genus Brugmansia species. The present review will be helpful for further research in the phytochemistry and pharmacology of Brugmansia species.Spatial discounting is a largely underexplored area of decision-making research, both theoretically and empirically, especially when compared to intertemporal choice, which has received significant attention in psychology and animal behaviour. Spatial decision problems seem to share some of the same features of a temporal decision problem (namely, the risk of reward objects disappearing and the opportunity cost of waiting), but there are several additional factors that affect the appropriate discount function for distant rewards. These include more significant opportunity costs, changes in the distances to all the other available opportunities, the post-reward costs of getting back home, the complex energetics associated with locomotion and all the additional risks faced by travelling itself. This paper organises and explores these factors and suggests some normative models that should predict the adaptive behaviour of animals and humans.

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