Effects of Qizhukangxian granules on idiopathic pulmonary fibrosis: a randomized, double blind, placebo-controlled and multicenter clinical pilot trial.

OBJECTIVE: To evaluate the effects of Qizhukangxian granules (QG) on idiopathic pulmonary fibrosis (IPF). METHODS: This is a randomized, double blind, placebo-controlled and multicenter clinical pilot trial. Six medical centers in Tianjin, China, participated in the study. A total of 120 IPF patients were enrolled and randomized into two groups, with 60 patients in each group. The treatment group was treated with QG, while the control group received a Qizhukangxian placebo. The pharmacological treatment lasted for 48 weeks from the enrollment date. The indexes of patients were recorded on the admission day and at the end of the 24th and 48th weeks. Data were analyzed to study the effects of QG; forced vital capacity, change in forced vital capacity and maximal 6-min walk test (6MWT) distance were the primary endpoints. Secondary endpoints were percentage of patients with episodes of acute exacerbation of IPF, pulmonary function, changes in pulse oxygen saturation during the 6MWT, dyspnea score, St. George's respiratory questionnaire score, arterial blood gas analyses and the total Traditional Chinese Medicine symptom pattern score. RESULTS: After 24 weeks of treatment, QG showed greater efficacy than the placebo in certain parameters, including the dyspnea score, Traditional Chinese Medicine symptom pattern score and some indicators in the St. George's respiratory questionnaire score. Analysis of the indexes obtained from all patients at the end of the 48th week showed that the therapeutic effects in the treatment group were significantly better than those in the control group because remarkable differences were observed in most of the primary and secondary endpoints between the two groups, except for the maximal distance of the 6MWT and arterial blood gas analyses. No adverse reaction was observed in either group during the 48-week trial treatment period. CONCLUSION: QG could effectively treat IPF patients by ameliorating pulmonary function, improving the quality of life and lowering the percentage of acute exacerbations.

Synergistic protection of matrine and lycopene against lipopolysaccharide­induced acute lung injury in mice.

Acute lung injury (ALI) is a major cause of morbidity and mortality globally, and is characterized by widespread inflammation in the lungs. Increased production of reactive oxygen species is hypothesized to be associated with ALI. Matrine and lycopene are active products present in traditional Chinese medicine. Matrine is an effective inhibitor of inflammation, whereas lycopene decreases lipid peroxidation. Therefore, it was hypothesized that combinatorial treatment with matrine and lycopene may provide synergistic protection against ALI. In the present study, mice were treated with dexamethasone (DEX; 5 mg/kg), matrine (25 mg/kg), lycopene (100 mg/kg), and matrine (25 mg/kg) + lycopene (100 mg/kg) for 7 days prior to injury induction using lipopolysaccharide (LPS; 5 mg/kg) for 6 h. Lung tissues were collected following the sacrifice of the mice and hematoxylin and eosin staining was used for histological analysis. Malondialdehyde (MDA), glutathione (GSH) and myeloperoxidas (MPO) levels were examined by respective kits. The expressions of interleukin­6 (IL­6) and tumor necrosis factor­α (TNF­α) were evaluated by ELISA. The expressions of IκBα and NF­κB p65 were examined by reverse transcription­quantitative polymerase chain reaction, western blotting and immunohistochemistry. The results indicated that the combined treatment exhibited a similar effect to DEX, both of which attenuated lung structural injuries, downregulated the expressions of IL­6, TNF­α, MPO and MDA, and upregulated that of GSH. Furthermore, the combined treatment and DEX inhibited NF­κB p65 activation. The present study revealed that combined treatment with matrine and lycopene exhibited protective effects on an LPS­induced mouse model of ALI, suggesting that they may serve as a potential alternative to glucocorticoid therapy for ALI.

Synthesis and discovery of a drug candidate for treatment of idiopathic pulmonary fibrosis through inhibition of TGF-ß1 pathway.

In this study, anti-IPF lead compounds 42 and 44, derived from natural sesquiterpene lactones Isoalantolactone and alantolactone, were discovered by screening from a high-throughput TGF-ß1 reporter luciferase assay. Notably, they could reduce the myofibroblast activation and extracellular matrix deposition both in vitro and in vivo. Additionally, compounds 42 and 44 could significantly attenuate bleomycin-induced pulmonary fibrosis in mice. Further validation of pharmacokinetics study and toxicity evaluation indicated that compound 44 might be a promising anti-IPF drug candidate.

The thalamus in cirrhotic patients with and without hepatic encephalopathy: a volumetric MRI study.

BACKGROUND & AIMS: The thalamus is a major relay and filter station in the central neural system. Some previous studies have suggested that the thalamus maybe implicated in the pathogenesis of hepatic encephalopathy. The aim of our study was to investigate changing thalamic volumes in cirrhotic patients with and without hepatic encephalopathy. METHODS: Neuropsychological tests and structural MR scanning were performed on 24 cirrhotic patients, 23 cirrhotic patients with minimal hepatic encephalopathy, 24 cirrhotic patients during their first episode of overt hepatic encephalopathy, and 33 healthy controls. Voxel-based morphometry analysis was performed to detect gray matter morphological changes. The thalamus and whole brain volume were extrapolated. A receiver operating characteristic curve analysis of thalamic volumes was used to discriminate patients with minimal hepatic encephalopathy from those with hepatic cirrhosis. RESULTS: Thalamic volume increased in a stepwise manner in patients with progressively worse stages of hepatic encephalopathy compared to healthy subjects. Additionally, a comparison of gray matter morphometry between patients with Child-Pugh grades A, B, or C and controls revealed a progression in thalamic volumes in parallel with the degree of liver failure. Moreover, thalamic volume was significantly correlated with the number connection test A time and digit-symbol test score in cirrhotic patients with minimal hepatic encephalopathy (r=0.659, P=0.001; r=-0.577, P=0.004; respectively). The area under the receiver operating characteristic curve was 0.827 (P=0.001). CONCLUSIONS: A significantly increased thalamic volume may be provide an objective imaging measure for predicting seizures due to minimal hepatic encephalopathy in cirrhotic patients.