Resolvin and lipoxin metabolism network regulated by Hyssopus Cuspidatus Boriss extract in asthmatic mice.

Resolvin (Rv) and lipoxin (Lx) play important regulative roles in the development of several inflammation-related diseases. The dysregulation of their metabolic network is believed to be closely related to the occurrence and development of asthma. The Hyssopus Cuspidatus Boriss extract (SXCF) has long been used as a treatment for asthma, while the mechanism of anti-inflammatory and anti-asthma action targeting Rv and Lx has not been thoroughly investigated. In this study, we aimed to investigate the effects of SXCF on Rv, Lx in ovalbumin (OVA)-sensitized asthmatic mice. The changes of Rv, Lx before and after drug administration were analyzed based on high sensitivity chromatography-multiple response monitoring (UHPLC-MRM) analysis and multivariate statistics. The pathology exploration included behavioral changes of mice, IgE in serum, cytokines in BALF, and lung tissue sections stained with H&E. It was found that SXCF significantly modulated the metabolic disturbance of Rv, Lx due to asthma. Its modulation effect was significantly better than that of dexamethasone and rosmarinic acid which is the first-line clinical medicine and the main component of Hyssopus Cuspidatus Boriss, respectively. SXCF is demonstrated to be a potential anti-asthmatic drug with significant disease-modifying effects on OVA-induced asthma. The modulation of Rv and Lx is a possible underlying mechanism of the SXCF effects.

Gentiopicroside Ameliorated Ductular Reaction and Inflammatory Response in DDC-induced Murine Cholangiopathies Model.

BACKGROUND: Cholangiopathies comprise a spectrum of diseases without curative treatments. Pharmacological treatments based on bile acid (BA) metabolism regulation represent promising therapeutic strategies for the treatment of cholangiopathies. Gentiopicroside (GPS), derived from the Chinese medicinal herb Gentianae Radix, exerts pharmacological effects on bile acid metabolism regulation and oxidative stress. OBJECTIVE: The present study aims to investigate the effect of GPS on 3,5-diethoxycarbonyl-1,4dihydrocollidine (DDC)-induced cholangiopathy. METHODS: Two independent animal experiments were designed to evaluate the comprehensive effect of GPS on chronic DDC diet-induced cholangiopathy, including bile duct obliteration, ductular reaction, BA metabolism reprogramming, liver fibrosis, oxidative stress and inflammatory responses. RESULTS: In the first pharmacological experiment, three doses of GPS (5, 25 and 125 mg/kg) were injected intraperitoneally into mice fed a DDC diet for 14 days. DDC induced a typical ductular reaction, increased periductal fibrosis and mixed inflammatory cell infiltration in the portal areas. GPS treatment showed dose-dependent improvements in the ductular reaction, BA metabolism, fibrosis, oxidative stress and inflammatory response. In the second experiment, a high dose of GPS was injected intraperitoneally into control mice for 28 days, resulting in no obvious histologic changes and significant serologic abnormalities in liver function. However, GPS inhibited DDC-induced oxidative stress, serum and hepatic BA accumulation, proinflammatory cytokine production, and immunocyte infiltration. Specifically, the GPS-treated groups showed decreased infiltration of monocyte-derived macrophages and CD4+ and CD8+ T lymphocytes, as well as preserved Kupffer cells. CONCLUSION: GPS alleviated chronic DDC diet-induced cholangiopathy disorder by improving the ductular reaction, periductal fibrosis, oxidative stress and inflammatory response. Its dosage-dependent pharmacological effects indicated that GPS warrants its further evaluation in clinical trials for cholangiopathy.

Costunolide alleviated DDC induced ductular reaction and inflammatory response in murine model of cholestatic liver disease.

Purpose: Cholestatic liver diseases are groups of hepatobiliary diseases without curative drug-based therapy options. Regulation of bile acid (BA) metabolism, hepatoperiductal fibrosis, and inflammatory response indicated present novel methods for the treatment of cholestatic liver disease. Costunolide (COS) from herb Saussurea lappa exerts a pharmacological effect of regulation of BA metabolism, liver fbrosis and inflammatory response. The present study aimed to clarify the pharmacodynamic effects of COS against the murine model of cholestatic liver disease. Methods: We established a murine model of cholestatic liver disease through chronic feeding of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet for 28 days. Two independent in vivo experiments were designed to reveal the pharmacological effect of COS against cholestatic liver disease. In the first experiment, two dosages of COS (10 and 30 mg/kg) were intraperitoneally injected into model mice daily for 14 days. In the second experiment, high dosage of COS (30 mg/kg) was intraperitoneally injected into control and model mice daily for 28 days. Results: In the evaluation of the hepatoprotective effect of COS, COS showed dosage-dependent improvement of cholestatic liver disease, including ductular reaction, hepatoperiductal fibrosis, and inflammatory response. The mechanism of COS-mediated hepatoprotective effects mainly relies on the regulation of BA metabolism, and the inflammatory response. DDC diet feed induced hepatic BA metabolism, transport and circulation dysfunction. COS treatment not only regulated the BA metabolism and transport gene, but also reprogrammed hepatic primary and secondary BA concentrations. DDC induced hepatic infiltrated monocytes derived macrophages and lymphocytes were inhibited, while Kupffer cells were preserved by COS treatment. The liver elevating inflammatory cytokines of DDC diet feed were alleviated by COS. Moreover, high dosage of 30 mg/kg COS treatment for 28 days resulted in no significant serological changes and no obvious hepatic histopathological changes when compared with control mice. Conclusion: COS protected against DDC diet feeding-induced cholestatic liver disease since COS regulated BA metabolism, ductular reaction, hepatoperiductal fibrosis and inflammatory response. COS is suggested as a potential natural product for the treatment of cholestatic liver disease.

[The latest research progress of tinnitus related treatment].

Tinnitus is a kind of phantom hearing. The quality of life of millions of people around the world is affected by it. There is no data to prove that drugs can be cured. There is no final conclusion on the clinical treatment of tinnitus. This article focuses on the treatment of tinnitus: Drug Treatment, Traditional Chinese Medicine, Surgical Treatment, Hyperbaric Oxygen Therapy, Acoustic Resonance Therapy, Transcranial Magnetic Stimulation Therapy, Cognitive Behavioral Therapy（CBT）, Tinnitus Retraining Therapy （TRT）, Multiple Compound Sound Therapy, etc. Provide more personalized tinnitus treatment programs for clinical patients.

Huoxue Jiedu Huayu Recipe Ameliorates Mesangial Cell Pyroptosis in Contralateral Kidney of UUO Rats.

OBJECTIVES: To observe the effects of the Huoxue Jiedu Huayu Recipe (HJHR) on pyroptosis of glomerular mesangial cells in the contralateral unobstructed kidney (CK) of unilateral ureteral obstruction (UUO) rats. METHODS: Sprague-Dawley rats were randomly divided into 4 groups: sham group, UUO group (10 days of left ureter ligation), UUO treated with eplerenone (EPL) (UUO + EPL) group, and UUO treated with HJHR (UUO + HJHR) group. The CKs of all rats were collected for studies. RESULTS: Cell pyroptosis and macrophage infiltration was found in contralateral glomeruli, and nucleotide-binding oligomerization domain-like pyrin domain containing protein 3 (NLRP3) and interleukin (IL)-1ß expression was upregulated in the CK of UUO rats. All of these changes were inhibited by HJHR and eplerenone. To determine how aldosterone (Aldo) activated the mineralocorticoid receptor (MR) and then induced mesangial cell pyroptosis with NLRP3-caspase-1-IL-1ß pathway, human mesangial cells (HMCs) were treated with HJHR and eplerenone, which were examined to detect the expression of NLRP3 inflammasome-associated proteins following treatment with Aldo. CONCLUSION: These results suggest that HJHR and eplerenone suppressed HMC pyroptosis via the MR/NLRP3 pathway.

Succinyl-proteome profiling of Dendrobium officinale, an important traditional Chinese orchid herb, revealed involvement of succinylation in the glycolysis pathway.

BACKGROUND: Lysine succinylation is a ubiquitous and important protein post-translational modification in various eukaryotic and prokaryotic cells. However, its functions in Dendrobium officinale, an important traditional Chinese orchid herb with high polysaccharide contents, are largely unknown. RESULTS: In our study, LC-MS/MS was used to identify the peptides that were enriched by immune-purification with a high-efficiency succinyl-lysine antibody. In total, 314 lysine succinylation sites in 207 proteins were identified. A gene ontology analysis showed that these proteins are associated with a wide range of cellular functions, from metabolic processes to stimuli responses. Moreover, two types of conserved succinylation motifs, '***Ksuc******K**' and '****EKsuc***', were identified. Our data showed that lysine succinylation occurred on five key enzymes in the glycolysis pathway. The numbers of average succinylation sites on these five enzymes in plants were lower than those in bacteria and mammals. Interestingly, two active site amino acids residues, K103 and K225, could be succinylated in fructose-bisphosphate aldolase, indicating a potential function of lysine succinylation in the regulation of glycolytic enzyme activities. Furthermore, the protein-protein interaction network for the succinylated proteins showed that several functional terms, such as glycolysis, TCA cycle, oxidative phosphorylation and ribosome, are consisted. CONCLUSIONS: Our results provide the first comprehensive view of the succinylome of D. officinale and may accelerate future biological investigations of succinylation in the synthesis of polysaccharides, which are major active ingredients.

The influence of compatibility of processed radix Aconiti Kusnezoffii on the pharmacokinetic of four components in Glycyrrhiza uralensis Fisch.

ETHNOPHARMACOLOGICAL RELEVANCE: Glycyrrhiza uralensis Fisch. and processed radix Aconiti kusnezoffii are the main components in many Chinese traditional patent medicines with the ratio of 1:1, which are used for treatment of rheumatoid arthritis, heart failure and so on. Glycyrrhizic acid, glycyrrhetic acid, liquiritigenin and isoliquiritigenin are the essential bioactive triterpenes and flavones in the extract of G. uralensis, which were analysis by a simple but accurate method. MATERIALS AND METHODS: In the present study, a specific HPLC method was developed and validated for simultaneous determination of pharmacokinetic parameters of glycyrrhizic acid, glycyrrhetic acid, liquiritigenin and isoliquiritigenin in G. uralensis after oral administration of single herb extract and a combination of two herbs extracts respectively. RESULTS: The calibration curves of the four components had good linearity higher than 0.9991 in the measured range. The intra-day and inter-day precisions (RSD) at different levels were both within 9.73%, and the accuracies (RE) were in the range of -7.9-8.0%. Compared with pharmacokinetic parameters of G. uralensis administered orally, values of AUC and Cmax of liquiritigenin and isoliquiritigenin decreased significantly (p<0.05), plasma concentrations of glycyrrhizic acid rose slightly and bimodal phenomenon of concentration-time of isoliquiritigenin and glycyrrhetinic acid disappeared after combined administration. DISCUSSION AND CONCLUSIONS: Some components in the extract of processed radix A. kusnezoffii showed different effects on the pharmacokinetics of the four ingredients in G. uralensis.

Study on hemostatic activities of the rhizome of Paris bashanensis.

UNLABELLED: CONTEXT. Paris bashanensis Wang et Tang (Liliaceae) is widely used in traditional Chinese medicine for the treatment of injuries, fractures and hemorrhage in Hubei and Sichuan Province. OBJECTIVE: The n-BuOH extract of Paris bashanensis was investigated for hemostatic activity and chemical constituents in order to provide a basis for the application in folk use. MATERIALS AND METHODS: The n-BuOH extract of P. bashanensis was divided into three eluents (30, 50 and 70% EtOH) by macroporous adsorptive resin D101. The bleeding time of breaking tail hemostasis and clotting time of capillary and slide method in mice were used extensively to screen the hemostasis properties after repetitive administration of these three fractions (100 mg/kg, 50 mg/kg) for 5 days (total of 5 times, once per day). The chemical compounds were analyzed by HPLC-UV. RESULTS: The inhibition rates in the bleeding time of 70, 50 and 30% n-BuOH ext. were 45, 32 and 21%, respectively. Using the slide method the decreasing rate of the clotting time of 70, 50 and 30% n-BuOH ext. were 71, 65 and 32% and in the experiment of capillary method, the inhibition rates were 43, 31 and 24%, respectively. A total of 70% n-BuOH ext. showed a high content of the pennogenin-type saponins by HPLC-UV. DISCUSSION AND CONCLUSIONS: The 70% n-BuOH ext. of P. bashanensis was found to contain high levels of pennogenin saponins, which may lead to a higher hemostatic activity. Combined with the hemostatic test, P. bashanensis could be used as a resource of hemostatic drug.