Corrigendum: Combination effect of three main constituents from Sarcandra glabra inhibits oxidative stress in the mice following acute lung injury: a role of MAPK-NF-κB pathway.

[This corrects the article DOI: 10.3389/fphar.2020.580064.].

Protection of procyanidin B2 on mitochondrial dynamics in sepsis associated acute kidney injury via promoting Nrf2 nuclear translocation.

In septic acute kidney injury (SAKI), the positive feedback between damaged mitochondria and accumulation of reactive oxygen species results in cell and tissue damage through multiple mechanisms. Removing the damaged mitochondria or neutralizing the reactive oxygen species has been considered beneficial to alleviating cell damage. The antioxidant Procyanidin B2 has been reported to inhibits reactive oxygen species and thereby reduces cell injury. However, it is unclear whether this effect is associated with clearance of damaged mitochondria. Here, we evaluated the efficacy of procyanidin B2 on SAKI, and focused on its effects on mitochondrial dynamics and removing damaged mitochondria via mitophagy. The results showed that the renal function, renal tubular cell vacuolization and oxidative stress were decreased in SAKI mice treated with procyanidin B2, moreover, skewed mitochondrial fusion/fission, mitochondrial mediated apoptosis and impaired mitophagy were improved in SAKI mice treated with procyanidin B2. In mechanism, the improvement of procyanidin B2 on mitochondrial dynamics were associated with increased nuclear translocation of the transcription factor, Nrf2. In summary, our findings highlighted that the protective efficacy of procyanidin B2 in reducing cellular damage in SAKI, and mechanisms improving mitochondrial dynamics and quality control at least in part by promoting Nrf2 translocation into the nucleus.

Combination Effect of Three Main Constituents From Sarcandra glabra Inhibits Oxidative Stress in the Mice Following Acute Lung Injury: A Role of MAPK-NF-κB Pathway.

Caffeoylquinic acids, coumarins and dicaffeoyl derivatives are considered to be three kinds of the most abundant bioactive components in Sarcandra glabra, an anti-inflammatory herb mainly found in Southern Asia. The combined anti-inflammatory effect of three typical constituents C + R + I (chlorogenic acid + rosmarinic acid + isofraxidin) from this plant has been investigated. The result implies that targeting the MAPK-NF-κB pathway would be one of the major mechanisms involved, using LPS stimulated RAW 264.7 cells as in vitro model and LPS-induced acute lung injury in mice as in vivo model. C + R + I can significantly suppress the levels of nitric oxide (NO), pro-inflammatory cytokines, and inhibit iNOS and COX-2 expression in LPS-treated RAW264.7 macrophage cells. Western blot analysis showed that C + R + I suppressed phosphorylation of NF-κB and MAPK, including phosphorylation of p65-NF-κB, IKB, ERK, JNK and P38. Besides, C + R + I suppressed MPO protein expression, but promoted SOD and HO-1 expression, and the related targets for C, R, and I were also predicted by molecular docking. This indicated that C + R + I could alleviate oxidative stress induced by LPS, which were further verified in the in vivo model of mice with acute lung injury through the measurement of corresponding inflammatory mediators and the analysis of immunehistochemistry.

Disturbance of mitochondrial dynamics and mitophagy in sepsis-induced acute kidney injury.

AIMS: The renal tubule cells require a large number of mitochondria to supply ATP due to their high-energy demand during reabsorption and secretion against chemical gradients and result in mitochondria susceptible to disorder and injury during stress conditions. Injured mitochondria are eventually degraded by mitophagy, and disturbances in mitophagy are associated with the pathogenesis of acute kidney injury (AKI) such as diabetic nephropathy and glomerulosclerosis. However, whether a disturbance in mitophagy has occurred and the role it plays in (SAKI) is still unclear. Therefore, the aim of this study was to investigate the key features of mitophagy and mitochondrial dynamics in sepsis-induced acute kidney injury (SAKI). MAIN METHODS: In this study, a murine septic AKI model induced by cecal ligation and puncture (CLP) was built; mitophagy and mitochondrial dynamics were measured in mice kidney in different time point. KEY FINDINGS: The results showed that mitochondrial dynamics were characterized by fission/fusion aberrant, however more inclined to fission, and mitochondrial associated apoptosis was elevated over-time during SAKI. Furthermore, mitophagy was impaired in the later phase of SAKI, although elevated in early stage of SAKI. The results indicate that the underlying mechanisms of impaired mitophagy may associate with the cleavage of Parkin via caspases activated by NLRP3, at least partly. SIGNIFICANCE: It is conceivable that this selective autophagic process and quality control machinery was impaired, leading to the accumulation of damaged mitochondria, oxidative stress, and cell death. Therefore, a targeted approach, by enhancing mitophagy during SAKI, may be a promising therapeutic strategy.

Protective effect of forsythoside B against lipopolysaccharide-induced acute lung injury by attenuating the TLR4/NF-κB pathway.

Acute lung injury (ALI), which is mainly triggered by infection, pneumonia, vasculitis, and sepsis, has no specific and effective therapy except for primary supportive treatment or bedside care. Excessive inflammation caused by innate immune cells is the major characteristic of ALI. Forsythoside B, a phenylethanoside compound, possesses good antioxidant and anti-bacterial properties in vivo and in vitro. In this study, the therapeutic potential of forsythoside B and its mechanism of action were investigated in a lipopolysaccharide (LPS)-induced ALI mouse model. The results showed that LPS-induced edema exudation and lung pathological changes in mice were significantly suppressed by forsythoside B pre-treatment. Furthermore, it also attenuated lung inflammation caused by LPS stimulation, evidenced by decreased inflammatory cell infiltration and down-regulated expression of cytokines, chemokines, and inducible enzymes. The anti-inflammation property of forsythoside B was confirmed in vitro using LPS-stimulated RAW 264.7 macrophages. Moreover, it alleviated LPS-induced inflammation by inhibiting the activation of TLR4/NF-κB signaling pathway in vivo and in vitro. In conclusion, the results demonstrated that forsythoside B protects against LPS-induced ALI by attenuating inflammatory cell infiltration and suppressing TLR4/NF-κB-mediated lung inflammation. Therefore, it might be a potential therapeutic agent for ALI caused by sepsis.

Diversity of Th1/Th2 immunity in mice with acute lung injury induced by the H1N1 influenza virus and lipopolysaccharides.

INTRODUCTION: The polarization of T helper (Th) cells plays an important role in the inflammatory response, pathogen removal, and tissue damage processes of infectious acute lung injury (ALI). However, Th cell polarization in viral- or bacterial-mediated ALI is not well defined. Herein, an influenza virus (A/FM/1/47, H1N1) and lipopolysaccharide (LPS) were chosen to induce ALI in mice, and the resultant diversity of Th-cell polarization was explored. METHODOLOGY: BALB/c mice were challenged intranasally with the influenza virus or LPS. Edema of the lung, infiltration of inflammatory cells (macrophages, neutrophils, and lymphocytes), oxidative stress, and signature cytokines of Th1 and Th2 cells were detected at 2 days post virus or LPS challenge. RESULTS: The mice exhibited increased capillary permeability accompanied by lung edema and protein-rich alveolar exudation after virus or LPS challenge. Additionally, excessive infiltration of inflammatory cells, robust oxidative stress, and cytokine production were observed in both mouse groups. However, there was conspicuous disparity in the inflammatory cell infiltration and cytokines between the virus- and LPS-challenged mice, where the infiltration in virus-challenged mice was mainly of macrophages and accompanied by robust Th1 cytokine elevation, whereas the infiltration in LPS-challenged mice was primarily of neutrophils and accompanied by robust Th2 cytokine elevation. CONCLUSIONS: The Th cell polarization was skewed depending on whether ALI was induced by the influenza virus or LPS. The polarization in the virus-challenged mice was primarily toward a Th1 response, whereas that in the LPS-challenged mice was mainly toward Th2.

Anti-inflammatory effects of rosmarinic acid-4-O-ß-D-glucoside in reducing acute lung injury in mice infected with influenza virus.

Rosmarinic acid-4-O-ß-D-glucoside (RAG) is a dicaffeoyl phenolic compound isolated from Sarcandra glabra (Thunb.) Nakai. Preliminary studies show that RAG has significant anti-inflammatory properties and can alleviate ear swelling in mice and the paw swelling in rats. Here, the anti-influenza effects of RAG were investigated in mice infected with A/FM/1/47 H1N1 virus. The survival rate and body weight were observed, the lung edema, virus copies, inflammatory cytokines (including IL-4, IL-5, TNF-α and IFN-γ) and oxidative damage indexes (including SOD, MDA, NO, and CAT) were measured. Moreover, immune cell recruitment in alveoli was measured with white blood cells and differential counts. Therapeutic RAG concentrations substantially improve the symptoms, mitigate body weight loss and alleviate lung edema induced by virus, thus improve survival protection effects. Furthermore, RAG was shown to regulate influenza virus-induced inflammatory cytokine expression, specifically by downregulating the Th1 cell cytokines IFN-γ, TNF-α and upregulating the Th2 cell cytokines IL-4, IL-5. Cell migration and infiltration were also diminished after RAG administration.

The roots of Ilex asprella extract lessens acute respiratory distress syndrome in mice induced by influenza virus.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, the root of Ilex asprella (Hook. & Arn.) Champ. ex Benth. (IA) has been widely used to treat influenza, lung abscess and other diseases in South China for many years. The present study is aimed at investigating the treatment effect of IA on acute respiratory distress syndrome (ARDS) induced by the H1N1 virus in mice. MATERIALS AND METHODS: After being inoculated with several viral doses of influenza A/FM/1/47 H1N1 virus, mice were given oral administration of IA extract (500 mg/kg or 12 5mg/kg per day) for five or 10 consecutive days, respectively. Mice survival rate and clinical condition were observed for 15 days after inoculation. Lung weight, pathological analysis and arterial blood gas analysis were assessed. Lung viral load was quantified by RT-PCR. Moreover, immunological analysis was measured by leukocyte counts and the levels of inflammatory cytokines, including IL-6, IL-10, TNF-α, IFN-γ, MCP-1 and IL-12p 70 in serum of mice. RESULTS: We found that the extract of Ilex asprella at dosages of 500 mg/kg could effectively diminish mortality rate, and ameliorate lung edema and inflammation. Administration of IA extract significantly depressed the expression of IL-6, TNF-α and MCP-1, and significantly increased the expression of IL-10 and IFN-γ in serum. Simultaneously, the extract was also found to reduce the lung viral load and improve pulmonary ventilation. CONCLUSION: The present study shows that the extract of IA has the potential to treat ARDS, due to its abilities of attenuation of systemic and pulmonary inflammatory responses and inhibition of viral replication.

Effects of geraniin on osteoclastic bone resorption and matrix metalloproteinase-9 expression.

In our previous studies, geraniin was reported to have a preventive effect in the rat model of tretinoin-induced osteoporosis. However, whether geraniin exhibits an inhibitory effect on bone resorption or on MMP-9 expression is not yet known. We present here our novel findings from in vitro experiments that geraniin (a) decreases the number of mature osteoclasts and pre-osteoclast in cultures, (b) reduces the osteoclastic fusion index, and (c) inhibits the resorption areas and resorption pits. We also report that geraniin suppresses the mRNA and protein expression levels of MMP-9. These results demonstrate that geraniin has an inhibitory effect on the bone-absorption ability of osteoclasts in vitro, and the mechanisms may be closely associated with the downregulation of mRNA and protein expression of MMP-9.

[Comparison of retrograde amnesia changes within different injury levels of cerebral concussion in rats].

OBJECTIVE: To investigate the retrograde amnesia changes within different injury levels of cerebral concussion in rats. METHODS: A metallic pendulum striker device of brain injury was deployed to duplicate CC models of different injury levels within Sprague-Dawley (S-D) rats. The investigated animals were divided into two groups according to classification standard, that is, Pure Cerebral Concussion (PCC) group and Complicated Cerebral Concussion (CCC) group. One control group was used, and each group included 8 animals. The retrograde amnesia of each group was assessed by Morris Water Maze (MWM) Test from 3 days preinjury to 7 days postconcussion. RESULTS: Compared with the control group, the retrograde amnesia was detected within 3 days in PCC group, and 5 days in CCC group after injury. At the same time, the two groups both manifested space recognition deficit. CONCLUSION: The retrograde amnesia existed in both pure cerebral concussion group and complicated cerebral concussion. Furthermore, the lasting time of retrograde amnesia in animals correlates to the injury level of brain concussion.

[Ecological footprint in building green university].

Ecological footprint is one of the best indexes to evaluate the level of green university. The approaches of ecological footprint are made up of compound approach and component approach. This paper introduces the basic principle and algorithm of the componential approach of ecological footprint, taking Northeastern University as an example and using this approach in the research of campus. Result show that the ecological footprint of Northeastern University 2003 was 24 787hm2, needing the productive land of ecology about 25 000hm2 support all kinds of consumption of the school and absorb the offal. The ecological efficiency of the school was 0.94cap/hm2. In the ecological footprints, the energy's footprints is the largest, it accounted for more than 2/3 of the total footprints, the next are food consumption and solid rubbish.