AIM:This study aimed to confirm the glycolytic inhibitory activity of 3-bromopyruvic acid(3BP)and to assess whether this inhibition could ameliorate hypoxia-induced pulmonary hypertension in rats.METHODS:PAH model rats were generated from normal SD rats via exposure to normal pressure and hypoxia.Intervention groups I and II(6 rats per group)were then intraperitoneally injected with 3BP(15 mg/kg),and the normal and hypoxia groups(6 rats per group)were given the same amount of normal saline for a total of 21 d.The average pulmonary artery pressure of the rats in each group was measured via right heart catheterisation,and hilar tissue measurements.The right ventricle(RV),left ventricle,and interventricular septum(LV+S)were weighed,and the ratio of RV/(LV+S)was calculated as an index of right ventricular hypertrophy.Right lower lung tissues were fixed in 4%paraformaldehyde-PBS buffer,sec-tioned in conventional paraffin(5 μm thick),stained with HE and Masson,photographed under a microscope.Then the thickness ratio of the tunica media and the area ratio of collagen fibres were calculated.The expression of pyruvate kinase isozyme type M2(PKM2),nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),and pyruvate de-hydrogenase(PDH)proteins in the hilar tissues of each group were detected by western blot,whereas interleukin-1β(IL-1β)and IL-18 contents were detected using ELISA,and lactic acid content was detected using a lactic acid kit.RE-SULTS:The results showed that 3-brpa effectively inhibited glycolysis and significantly improved hypoxia-induced pulmo-nary hypertension in rats.Compared with the hypoxia group,in intervention group II,PKM2 expression was decreased(P<0.05),PDH expression increased significantly(P<0.01),and NLRP3 expression was decreased(P<0.05).The IL-18 and IL-1β contents decreased(P<0.05 or P<0.01,respectively).Pulmonary hemodynamic indexes showed that the pro-portion of the right ventricle and the mean pressure of the pulmonary artery decreased(P<0.05 or P<0.01,respectively).The HE and Masson staining results showed that the thickness ratio of the tunica media and the area ratio of collagen fibres decreased significantly(P<0.01).Lactic acid content was significantly decreased(P<0.01).CONCLUSION:This study showed that 3BP can inhibit glycolysis and alleviate hypoxia-induced pulmonary hypertension in rats.

AIM:This study aimed to confirm the glycolytic inhibitory activity of 3-bromopyruvic acid(3BP)and to assess whether this inhibition could ameliorate hypoxia-induced pulmonary hypertension in rats.METHODS:PAH model rats were generated from normal SD rats via exposure to normal pressure and hypoxia.Intervention groups I and II(6 rats per group)were then intraperitoneally injected with 3BP(15 mg/kg),and the normal and hypoxia groups(6 rats per group)were given the same amount of normal saline for a total of 21 d.The average pulmonary artery pressure of the rats in each group was measured via right heart catheterisation,and hilar tissue measurements.The right ventricle(RV),left ventricle,and interventricular septum(LV+S)were weighed,and the ratio of RV/(LV+S)was calculated as an index of right ventricular hypertrophy.Right lower lung tissues were fixed in 4%paraformaldehyde-PBS buffer,sec-tioned in conventional paraffin(5 μm thick),stained with HE and Masson,photographed under a microscope.Then the thickness ratio of the tunica media and the area ratio of collagen fibres were calculated.The expression of pyruvate kinase isozyme type M2(PKM2),nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),and pyruvate de-hydrogenase(PDH)proteins in the hilar tissues of each group were detected by western blot,whereas interleukin-1β(IL-1β)and IL-18 contents were detected using ELISA,and lactic acid content was detected using a lactic acid kit.RE-SULTS:The results showed that 3-brpa effectively inhibited glycolysis and significantly improved hypoxia-induced pulmo-nary hypertension in rats.Compared with the hypoxia group,in intervention group II,PKM2 expression was decreased(P<0.05),PDH expression increased significantly(P<0.01),and NLRP3 expression was decreased(P<0.05).The IL-18 and IL-1β contents decreased(P<0.05 or P<0.01,respectively).Pulmonary hemodynamic indexes showed that the pro-portion of the right ventricle and the mean pressure of the pulmonary artery decreased(P<0.05 or P<0.01,respectively).The HE and Masson staining results showed that the thickness ratio of the tunica media and the area ratio of collagen fibres decreased significantly(P<0.01).Lactic acid content was significantly decreased(P<0.01).CONCLUSION:This study showed that 3BP can inhibit glycolysis and alleviate hypoxia-induced pulmonary hypertension in rats.

Background/Aims: Oral EDP-514 is a potent core protein inhibitor of hepatitis B virus (HBV) replication, which produced a >4-log viral load reduction in HBV-infected chimeric mice with human liver cells. This study evaluated the safety, pharmacokinetics, and antiviral activity of three doses of EDP-514 in treatment-naive viremic patients with HBeAgpositive or -negative chronic HBV infection. Methods: Patients with HBsAg detectable at screening and at least 6 months previously were eligible. HBeAg-positive and -negative patients had a serum/plasma HBV DNA level ≥20,000 and ≥2,000 IU/mL, respectively. Twenty-five patients were randomized to EDP-514 200 (n=6), 400 (n=6) or 800 mg (n=7) or placebo (n=6) once daily for 28 days. Results: A dose-related increase in EDP-514 exposure (AUClast and Cmax) was observed across doses. At Day 28, mean reductions in HBV DNA were –2.9, –3.3, –3.5 and –0.2 log10 IU/mL with EDP-514 200 mg, 400 mg, 800 mg, and placebo groups, respectively. The corresponding mean change from baseline for HBV RNA levels was –2.9, –2.4, –2.0, and –0.02 log10 U/mL. No virologic failures were observed. No clinically meaningful changes from baseline were observed for HBsAg, HBeAg or HBcrAg. Nine patients reported treatment emergent adverse events of mild or moderate severity with no discontinuations, serious AEs or deaths. Conclusions In treatment-naïve viremic patients, oral EDP-514 was generally safe and well-tolerated, displayed PK profile supportive of once-daily dosing, and markedly reduced HBV DNA and HBV RNA.

Sojae Semen Germinatum was firstly recorded in Shennong Bencaojing， and it has a long history of edible and medicinal use. Most ancient medical practitioners described that Sojae Semen Germinatum was processed with black soya bean， while some others recorded that Sojae Semen Germinatum was processed with black soya bean and soybean or with soybean only. In modern times， black soya bean and soybean are both used. Before the Northern and Southern dynasties， the germination process of Sojae Semen Germinatum was mostly soil culture， and then changed into water culture later. The medicinal part of Sojae Semen Germinatum may also change from the initial aboveground part to the whole processed products including the soybean and the bud. The bud length was used to control the processing ending of Sojae Semen Germinatum， but there were different views of the bud length in ancient and modern times. Before the Tang dynasty， Sojae Semen Germinatum was mostly used directly. Since the Tang dynasty， various subsequent processed products of Sojae Semen Germinatum appeared. Most ancient medical practitioners confirmed that Sojae Semen Germinatum was sweet flavor， neutral in nature and non-toxic， and the mainstream believed that it belonged to the spleen， lung and stomach meridians. However， there were different opinions on its efficacy of relieving exterior syndrome by diaphoresis. In this paper， the evolution of Sojae Semen Germinatum was explored after consulting all kinds of ancient books， its historical name， processing history， quality evaluation and others were systematically summarized in order to clarify its historical development and lay a good foundation for the clinical use and further development of Sojae Semen Germinatum.

The purpose of this study was to understand the pharmacodynamic effect of Valeriana jatamansi extract in diarrhea predominant irritable bowel syndrome(IBS-D) rat model induced by maternal separation combined with three kinds of stress, and observe the changes of endogenous metabolites in feces after intervention to find potential biomarkers and related metabolic pathways. The animal model of IBS-D was established by maternal separation combined with restraint, ice swimming and tail clamping. The therapeutic effect of each dose group of V. jatamansi extract was evaluated in terms of abdominal withdrawal reflex pressure threshold, fecal water content and immobility time of forced swimming test. In addition, rat feces were collected for detection of metabolic profiles of small molecular metabolites with UPLC-LTQ-Orbitrap MS platform, so as to find the biomarkers of differential metabolism with multivariate statistical analysis methods such as principal component analysis(PCA) and orthogon partial least squares discrimination analysis(OPLS-DA). The results showed that as compared with the normal group, the threshold of abdominal withdrawal reflex pressure was decreased, the fecal water content was increased, and the immobility time of forced swimming test was prolonged in the model group. The results of fecal metabonomics showed that the levels of 39 metabolites were down-regulated and those of 37 metabolites were up-re-gulated. Further analysis showed that these metabolites were related to bile acid metabolism, unsaturated fatty acid metabolism, amino acid metabolism, ceramide metabolism and other metabolic pathways. This study proved that the extract of V. jatamansi had definite pharmacodynamic effect on IBS-D model rats, and the mechanism was discussed from the perspective of fecal metabonomics.
Animals ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Diarrhea ; Feces ; Irritable Bowel Syndrome/drug therapy* ; Maternal Deprivation ; Metabolomics ; Rats ; Tandem Mass Spectrometry ; Valerian

Artemisiae Annuae Herba is a traditional Chinese medicine for clearing deficiency and heat. It is the only natural source of artemisinin, which is a specific antimalarial drug, and has been widely concerned all over the world. In addition to artemisinin, Artemisiae Annuae Herba also contains many sesquiterpenes, coumarins, flavonoids, volatile oils, polysaccharides and other chemical components, which show antipyretic, anti-inflammatory, antiviral microorganisms, anti-asthma, anti-oxidation, anti-tumor and other pharmacological activities. In addition to their own pharmacological activities, some components could enhance the antimalarial activity of artemisinin through different mechanisms at absorption and metabolism in vivo. In order to understand the pharmacokinetic characte-ristics of the chemical constituents contained in Artemisiae Annuae Herba and provide reference for the full development and clinical utilization of Artemisiae Annuae Herba resources in China, this present paper systematically collated the modern research literatures, and summarized the biosynthesis, in vivo analysis and pharmacokinetics of the chemical constituents in Artemisiae Annuae Herba.
Antimalarials ; China ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Oils, Volatile

Objective:To study the antitumor effect of Xihuangwan on A549 lung cancer nude mice in inflammatory microenvironment, and explore the effect of Xihuangwan on the expressions of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammatory bodies and their products in serum and tumor tissue of A549 lung cancer nude mice. Method:The lung cancer A549 cell model was established in nude mice with lung cancer, and the lung cancer A549 cell model was established in inflammatory microenvironment by adding lipopolysaccharide (LPS) + adenosine triphosphate (ATP) to the culture medium. After modeling, the rats were randomly divided into blank group (equal volume of normal saline), positive drug control group (MCC950 solution, 0.79 g·kg^-1), and low, medium, high-dose Xihuangwan groups (0.39, 0.78, 1.95 g·kg^-1). The rats were administered orally once a day for 21 days, and then sacrificed. The tumor tissues were stripped to measure the tumor body. The expressions of NLRP3, malondialdehyde（MDA）, interleukin (IL)-1β, IL-18 and NLRP3 were detected by Western blot, and the levels of IL-1β, IL-18 and MDA were detected by enzyme linked immunosorbent assay（ELISA）. Result:Compared with the blank group, the tumor inhibition rates in the positive drug control group and the low, medium and high dose Xihuangwan group were 39.21%, 31.72%, 42.24% and 55.68%. ELISA showed that the high-dose Xihuangwan group could significantly reduce the expressions of MDA, IL-1β and IL-18 in the serum of nude mice (P<0.05). Western blot showed that the high-dose Xihuangwan group could effectively reduce the protein expressions of MDA, IL-1β, IL-18 and NLRP3 in tumor of nude mice (P<0.05), the results of immunohistochemistry showed that the expression rate of NLRP3 in the tumor tissues of nude mice was reduced in the positive drug group and each dose of Xihuangwan group (P<0.05). Conclusion:Xihuangwan can inhibit the growth of tumor tissue of A549 cells bearing lung cancer in nude mice. The mechanism may be that it can inhibit the growth of tumor cells by inhibiting the expression of NLRP3 inflammatory bodies, IL-1β, IL-18, MDA tables, and then inhibiting the inflammatory microenvironment of tumor cells.