Exploring the protective effect of Sangggua Drink against type 2 diabetes mellitus in db/db mice using a network pharmacological approach and experimental validation.

Sanggua Drink (SGD) is an experienced formula for clinical treatment of type 2 diabetes mellitus (T2DM). Network pharmacology and experiments were combined to explore the potential mechanism of action of SGD on T2DM. The material basis and action mechanism of SGD were investigated to reveal the active components of SGD, potential target prediction was conducted from TargetNet, PharmMapper; Cytoscape was used to construct PPI network and component-target-pathway (C-T-P) network diagram to interpret biological processes and enrich action pathways. 54 compounds and 41 key target proteins were screened, and a total of 98 signaling pathways were obtained. In vivo experiments, the levels of p-AMPK (P < 0.01), p-ACC and p-AKT were significantly increased in the mice with SGD intervention compared to the db/db mice, while level of FOXO1 were decreased. The results suggested that SGD might improve insulin resistance and glucose metabolism in T2DM mice by activating the AMPK/Akt signaling pathway.

Tetrandrine Represses Inflammation and Attenuates Osteoarthritis by Selective Inhibition of COX-2.

OBJECTIVE: There is a lack of effective and long-term safe drugs for the treatment of osteoarthritis (OA). Tetrandrine (Tet) has been approved and used to treat rheumatoid arthritis for several decades, but its effect on OA has not been investigated. Herein, we explored the effect of Tet on OA and its underlying mechanism. METHODS: OA was induced using destabilization of the medial meniscus (DMM) in C57BL/6J mice. The animals were randomly divided into sham, DMM, Tet, celecoxib (CXB), and indomethacin (INDO) groups. Each group was given solvent or corresponding drugs by gavage for 7 weeks after convalescence. Pathological staining, OARSI scores, micro-computed tomography and behavior tests were performed to evaluate the effects of Tet. RESULTS: Tet remarkably alleviated cartilage injury in the knee joint, limited bone remodeling in the subchondral bone, and delayed progression of OA. Tet also significantly relieved joint pain and maintained function. Further mechanistic studies revealed that Tet lowered inflammatory cytokine levels and selectively suppressed gene and protein expression of cyclooxygenase (COX)-2 but not COX-1 (P<0.01). Tet also reduced the production of prostaglandin E2 without damaging the gastric mucosa. CONCLUSION: We found that Tet could selectively inhibit COX-2 gene expression and decrease cytokine levels in mice, thus reducing inflammation and improving OA without obvious gastric adverse events. These results provide a scientific basis for the clinical application of Tet in the treatment of OA.

Cariporide Attenuates Doxorubicin-Induced Cardiotoxicity in Rats by Inhibiting Oxidative Stress, Inflammation and Apoptosis Partly Through Regulation of Akt/GSK-3ß and Sirt1 Signaling Pathway.

Background: Doxorubicin (DOX) is a potent chemotherapeutic agent with limited usage due to its cumulative cardiotoxicity. The Na+/H+ exchanger isoform 1 (NHE1) is a known regulator of oxidative stress, inflammation, and apoptosis. The present study was designed to investigate the possible protective effect of cariporide (CAR), a selective inhibitor of NHE1, against DOX-induced cardiotoxicity in rats. Methods: Male Sprague-Dawley rats were intraperitoneally injected with DOX to induce cardiac toxicity and CAR was given orally for treatment. The injured H9c2 cell model was established by incubation with DOX in vitro. Echocardiography, as well as morphological and ultra-structural examination were performed to evaluate cardiac function and histopathological changes. The biochemical parameters were determined according to the manufacturer's guideline of kits. ROS were assessed by using an immunofluorescence assay. The serum levels and mRNA expressions of inflammatory cytokines were measured by using ELISA or qRT-PCR. Cardiac cell apoptosis and H9c2 cell viability were tested by TUNEL or MTT method respectively. The protein expressions of Cleaved-Caspase-3, Bcl-2, Bax, Akt, GSK-3ß, and Sirt1 were detected by western blot. Results: Treatment with CAR protected against DOX-induced body weight changes, impairment of heart function, leakage of cardiac enzymes, and heart histopathological damage. In addition, CAR significantly attenuated oxidative stress and inhibited the levels and mRNA expressions of inflammatory cytokines (TNF-α, IL-6, IL-18, and IL-1ß), which were increased by DOX treatment. Moreover, CAR significantly suppressed myocardial apoptosis and Cleaved-Caspase-3 protein expression induced by DOX, which was in agreement with the increased Bcl-2/Bax ratio. Also, DOX suppressed phosphorylation of Akt and GSK-3ß, which was significantly reversed by administration of CAR. Furthermore, CAR treatment prevented DOX-induced down-regulation of Sirt1 at the protein level in vitro and in vivo. Finally, Sirt1 inhibitor reversed the protective effects of CAR, as evidenced by reduced cell viability and Sirt1 protein expression in vitro. Conclusion: Taken together, we provide evidence for the first time in the current study that CAR exerts potent protective effects against DOX-induced cardiotoxicity in rats. This cardio-protective effect is attributed to suppressing oxidative stress, inflammation, and apoptosis, at least in part, through regulation of Akt/GSK-3ß and Sirt1 signaling pathway, which has not been reported to date.

Treatment of landfill leachate biochemical effluent using the nano-Fe3O4/Na2S2O8 system: Oxidation performance, wastewater spectral analysis, and activator characterization.

Nano-Fe3O4 was used as heterogeneous catalyst to activate Na2S2O8 for the generation of the sulfate radicals (SO4-) to oxidize the residual pollutants in landfill leachate biochemical effluent. The oxidation performance, wastewater spectral analysis and activator characterization were discussed. Oxidation experimental result shows that nano-Fe3O4 has obvious catalytic effect on Na2S2O8 and can significantly enhance the oxidation efficiencies of Na2S2O8 on landfill leachate biochemical effluent, with COD and color removals above 63% and 95%, respectively. Based on the analyses of three-dimensional excitation emission matrix fluorescence spectrum (3DEEM), ultraviolet-visible spectra (UV-vis), and Fourier Transform infrared spectroscopy (FTIR) of wastewater samples before and after treatment, it can be concluded that the pollution level of dissolved organic matter (DOM) declined and that the humic acid (HA) fractions were efficiently degraded into small molecules of fulvic acid (FA) fractions with less weight and stable structure. Compared to the raw wastewater sample, the aromaticity and substituent groups of the DOM were lessened in the treated wastewater sample. Moreover, the main structure of the organics and functional groups were changed by the Fe3O4/Na2S2O8 system, with substantial decrease of conjugated double bonds. The micro morphology of nano-Fe3O4 was characterized before and after reaction by the methods of scanning electron microscope spectra (SEM), X-ray diffraction pattern (XRD), and X-ray photoelectron spectroscopy (XPS). The XRD pattern analysis showed that nano-Fe3O4 was oxidized into r-Fe2O3 and that the particle size of it also became smaller after reaction. XPS was employed to analyze the content and iron valence on the nano-Fe3O4 surface, and it can be found that the ratio of Fe3+/Fe2+ decreased from 1.8 before reaction to 0.8 after reaction. From the SEM analysis after the treatment, it was determined that the spacing between nano-Fe3O4 was increased, but in turn, the particles decreased in diameter.