Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney, and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways.

BACKGROUND: Jianpi Gushen Huayu Decoction (JPGS) has been used to clinically treat diabetic nephropathy (DN) for many years. However, the protective mechanism of JPGS in treating DN remains unclear. AIM: To evaluate the therapeutic effects and the possible mechanism of JPGS on DN. METHODS: We first evaluated the therapeutic potential of JPGS on a DN mouse model. We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics. Furthermore, we examined the effects of JPGS on c-Jun N-terminal kinase (JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3). RESULTS: The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress. Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice. A total of 51 differential metabolites were screened. Pathway analysis results indicated that nine pathways significantly changed between the control and model groups, while six pathways significantly altered between the model and JPGS groups. Pathways related to cysteine and methionine metabolism; alanine, tryptophan metabolism; aspartate and glutamate metabolism; and riboflavin metabolism were identified as the key pathways through which JPGS affects DN. Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors. CONCLUSION: JPGS could markedly treat mice with streptozotocin (STZ)-induced DN, which is possibly related to the regulation of several metabolic pathways found in kidneys. Furthermore, JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathway-mediated apoptosis in DN mice.

Mechanical study of alisol B 23-acetate on methionine and choline deficient diet-induced nonalcoholic steatohepatitis based on untargeted metabolomics.

Alisol B 23-acetate (AB23A) has been demonstrated to have beneficial effects on nonalcoholic steatohepatitis (NASH). However, the mechanisms of AB23A on NASH remain unclear. This study aimed to investigate the mechanisms underlying the metabolic regulatory effects of AB23A on NASH. We used AB23A to treat mice with NASH, which was induced by a methionine and choline deficient (MCD) diet. We initially investigated therapeutic effect and resistance to oxidation and inflammation of AB23A on NASH. Subsequently, we performed untargeted metabolomic analyses and relative validation assessments to evaluate the metabolic regulatory effects of AB23A. AB23A reduced lipid accumulation, ameliorated oxidative stress and decreased pro-inflammatory cytokines in the liver. Untargeted metabolomic analysis found that AB23A altered the metabolites of liver. A total of 55 differential metabolites and three common changed pathways were screened among the control, model and AB23A treatment groups. Further tests validated the effects of AB23A on modulating common changed pathway-involved factors. AB23A treatment can ameliorate NASH by inhibiting oxidative stress and inflammation. The mechanism of AB23A on NASH may be related to the regulation of alanine, aspartate and glutamate metabolism, d-glutamine and d-glutamate metabolism, and arginine biosynthesis pathways.

[Protective mechanism on the vascular pathological process in diabetes mellitus rats by Rheum officeinale].

OBJECTIVE: To explore the protective mechanism of officeihale on the vascular pathological process in diabetes mellitus (DM) rats. METHOD: After the DM rat model was established, 24 DM rats were randomly divided into model group (12 DM rats) and Rheum officeinale group (12 DM rats). Rheum officeinale was orally given in 10 g kg(-1) per day, and the other two groups were given equal pure water. 8 weeks later, blood samples were collected to determine the level of nitric oxide (NO) and endothelin-1 (ET-1). Thoracic aortic rings was prepared to observe the inhibiting effect of Ach with different concentration on contraction caused by NE. Another part of aorta was made to observe the expression of ICAM-1 and VCAM-1 by method of SP immunohistochemistry staining, RESULT: Rheum officeinale group obviously decreased the level of ET-1 and increased the NO compared with model group (P <0.05). The expression of ICAM-1 and VCAM-1 could be obviously inhibited in Rheum officeinale group compared with model group. (P <0.05). CONCLUSION: Rheum officeinale could decrease the level of ET-1 with increased the NO in diabetes rats, and inhibit the expression of ICAM-1 and VCAM-1, which may be mechanisms of protecting the endothelium of vessel in diabetes rats.

[Observation on the ultrastructure of Pneumocystis carinii].

OBJECTIVE: To study the life cycle and morphology of Pneumocystis carinii by ultrastructural observation. METHODS: Wistar rat model of P. carinii infection was established by subcutaneous injection with dexamethasone. Lung tissue of the infected rats was used for the transmission electron microscopical study. RESULTS: The organisms were mainly present in the lung alveolar cavity, and also in the alveolar septum, pulmonary macrophages and neutrophils. More trophozoites of P. carinii attached to the type I alveolar epithelial cells, and rarely to the type II alveolar epithelial cells. Most of these trophozoites showed pseudopodial evaginations on their pellicles. The nucleus-associated organelle and spindle microtubules were observed in some trophozoites. The precyst phase was in three forms: early, intermediate and late form. Synaptonemal complexes indicating meiotic nuclear divisions and a clump of mitochondria were also observed in the precyst. The pellicle of the cyst has a thickened portion with a pore. There were nucleus with nucleolus, mitochondrion, vesicles, endoplasmic reticulum and numerous ribosomes in the organisms, and tubular expansions on its surface. CONCLUSION: The life cycle of P. carinii consists of trophozoite, precyst and cyst stages. The presence of a single pore in the cyst wall reveals that pore formation may be a mode of excystation for intracystic bodies of P. carinii.