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Objective The Huanghuai (HH), which is made from the dried roots of Scutellaria baicalensis (Huangqin in Chinese) and the dried flowers and buds of Sophora japonica (Huaihua in Chinese), is a traditional Chinese formula used to treat dysfunctional uterine bleeding (DUB) (Benglou in Chinese) and proven to treat hemostasis effectively in our previous study. Network pharmacology and molecule docking were performed to study the underlying mechanism of Huanghuai (HH), and pharmacodynamic experiments were conducted to verify its curative effect. Methods TCMSP, UniProt, GeneCards, STRING, DAVID databases, and Cytoscape 3.7.2 were utilized for the construction of a compound-target-pathway network. Docking the potential effective components with potential targets. The HPLC analysis of the potential effective components was performed. In vivo, the hot plate test model was used to study the analgesic activity, the egg white was used to study the swollen reaction in the sole in mice, and the hemostasis effect was studied by the capillary method, tail-breaking method and abortion uterus test. Results The results showed that six compounds (acacetin, beta-sitosterol, wogonin, baicalein, kaempferol and quercetin) and four potential targets (PTGS2, AKT1, TP53 and TNF) in the compound-target-pathway network were the potential material basis for HH to treat DUB. It can be seen that the binding energy of the acacetin, wogonin, baicalein, beta-sitosterol, kaempferol and quercetin in HH docked with the receptor proteins PTGS2, AKT1, TP53, and TNF were far less than −5.0 kJ/mol, which means the molecules have low conformational energy, stable structure and high binding activity. And the result of HPLC analysis showed that acacetin, wogonin, baicalein, kaempferol and quercetin were the potential effective components of the hemostasis mechanism of HH, beta-sitosterol was removed due to low content. In vivo testing of the potential effective components, it revealed that the group of potential effective components identified by HPLC could increase the pain threshold, inhibit the swelling hind paws of mice induced by egg white, reduce the bleeding time and clotting time, reduce uterine bleeding, decrease the uterine weight, increase the content of Ca and ET-1, and reduce the content of NO in uterine homogenate tissue, and decrease of E2 and P content in uterine serum in aborted rats, whose efficacy was equal to HH. Conclusion The results indicated that HH and potential active ingredient groups obtained from network pharmacology can treat DUB and play a hemostatic effect. The results obtained by network pharmacology have certain reliability. This study provides new indications for further mechanism research of HH on DUB and the development of HH or its components as an alternative therapy for patients with DUB. At the same time, the application of network pharmacology strategy may provide a powerful tool for exploring the mechanism of traditional Chinese medicine and discovering new biologically active ingredients.

Background Vaccination is the most efficient means for protection against influenza. However, the various vaccines have low efficacy to protect against pandemic strains because of antigenic drift and recombination of influenza virus. Adjuvant therapy is one of the attempts to improve influenza vaccine effective cross-protection against influenza virus infection. Our previous study confirmed that 1,8-cineole inhibits the NF-κB, reduces pro-inflammatory cytokines, and relieves the pathological changes of viral pneumonia in mice infected with influenza virus. Hypothesis/Purpose 1,8-cineole, administered via intranasal (i.n.) route, may also have the capacity to be an adjuvant of the influenza vaccine. This study was designed to investigate the potential use of i.n. co-administration of 1,8-cineole, a major component of the Eucalyptus essential oils, with influenza vaccine and whether could provide cross-protection against influenza virus infection in a mouse model. Study design I.n. co-administration of 1,8-cineole in two doses (6.25 and 12.5 mg/kg) with influenza vaccine was investigated in a mouse model in order to see whether it could provide cross-protection against influenza virus infection. Methods The mice were intranasally immunized three times at the 0, 7 and 14 day with vaccine containing 0.2 µg hemagglutinin (HA) and/or without 1,8-cineole. Seven days after the 3rd immunization dose, the mice were infected with 50 µl of 15 LD50 (50% mouse lethal dose) influenza virus A/FM/1/47 (H1N1). On day 6 post-infection, 10 mice per group were sacrificed to collect samples, to take the body weight and lung, and detect the viral load, pathological changes in the lungs and antibody, etc. The collected samples included blood serum and nasal lavage fluids. In addition, the survival experiments were carried out to investigate the survival of mice. Results Mice i.n. inoculated with influenza vaccine and 12.5 mg/kg 1,8-cineole increased the production of influenza-specific serum immunoglobulin (Ig) G2a antibodies, stimulated mucosal secretive IgA (s-IgA) responses at the nasal cavity, improved the expression of respiratory tract intraepithelial lymphocytes (IELs) in the upper respiratory tract, and promoted dendritic cell (DC) maturation and the expression of co-stimulatory molecules cluster of differentiation (CD)40, CD80 and CD86 in peripheral blood. Importantly, mice that had received 1,8-cineole-supplemented influenza vaccine showed longer survival time, milder inflammation, less weight loss and mortality rate and lower lung index and viral titers compared to that of mice immunized a non-1,8-cineole-adjuvanted split vaccine. Thus, i.n. immunization with 1,8-cineole-adjuvanted vaccine induces a superior cross-protective immunity against infection with influenza than an inactivated vaccine only. Conclusion These results suggest that 1,8-cineole (12.5 mg/kg) has a cross-protection against influenza virus, co-administered with inactivated influenza viral antigen in a mouse model.

Sepsis-induced liver injury is very common in intensive care units. Here, we investigated the effects of 6-gingerol on sepsis-induced liver injury and the role of the Nrf2 pathway in this process. 6-Gingerol is the principal ingredient of ginger that exerts anti-inflammatory and antioxidant effects. Using cecal ligation and puncture (CLP) to induce polymicrobial sepsis and related liver injury, we found that mice pre-treated with 6-Gingerol showed less incidences of severe liver inflammation and death than untreated CLP groups. 6-Gingerol administration also inhibited the expression of pyroptosis-related proteins, including NOD-like receptor protein 3 (NLRP3), IL-1β, and caspase-1. Consistent with these findings, 6-gingerol reduced the effects of pyroptosis induced by lipopolysaccharide (LPS) and adenosine 5'-triphosphate (ATP) in RAW 264.7 cells, as evidenced by IL-1β and caspase-1 protein levels in the supernatant and propidium iodide (PI) staining. 6-Gingerol was shown to activate the Nrf2 pathway in vivo and in vitro. Notably, Nrf2 siRNA transfection nullified the inhibitory effects of 6-gingerol on pyroptosis in vitro. In summary, these findings suggested that 6-gingerol alleviated sepsis-induced liver injury by inhibiting pyroptosis through the Nrf2 pathway.

As the sulfide ore deposits become less economical and environmental viable as a source of nickel, increasing attention is being paid to the laterite ores. But in the pyrometallurgical process of laterite, more efforts should be paid to control the reduction of iron oxide in order to get high nickel-content nickeliferous product. For these reasons, equilibrium condition of iron oxide when laterite ore was selectively reduced by CO2/CO, H2O/H2 and CO2/H2 was studied from the perspective of iron activity with an assumption that the activities of FeO and Fe3O4 equal 1 in this work, and it well accounts for the inescapability of Fe metallization. Activity coefficient of iron in Ni–Fe binary solid alloy was calculated by Miedema model based on the known thermodynamics datum filed. According to Raoult's law, the relationship among the Fe/Ni ratio, reduction temperature and reduction gas composition was calculated when laterite ore was selectively reduced by the three different reduction systems. The calculation result was discussed and also compared with the experimental result. The trend of metal iron content in the reduction product of laterite ore varying with temperature and gas composition was well predicted by the calculation result.