Berberine Regulates GPX4 to Inhibit Ferroptosis of Islet ß Cells.

Ferroptosis, as a kind of non-apoptotic cell death, is involved in the pathogenesis of type 1 diabetes mellitus (T1DM). Islet B cells mainly produce insulin that is used to treat diabetes. Berberine (BBR) can ameliorate type 2 diabetes and insulin resistance in many ways. However, a few clues concerning the mechanism of BBR regulating ferroptosis of islet ß cells in T1DM have been detected so far. We measured the effects of BBR and GPX4 on islet ß cell viability and proliferation by MTT and colony formation assays. Western blot and qRT-PCR were utilized to examine GPX4 expression in islet ß cells with distinct treatments. The influence of BBR and GPX4 on ferroptosis of islet ß cells was investigated by evaluating the content of Fe2+ and reactive oxygen species (ROS) in cells. The mechanism of BBR targeting GPX4 to inhibit ferroptosis of islet ß cells was further revealed by the rescue experiment. Our results showed that BBR and overexpression of GPX4 could notably accelerate cell viability and the proliferative abilities of islet ß cells. Moreover, BBR stimulated GPX4 expression to reduce the content of Fe2+ and ROS, thereby repressing the ferroptosis of islet ß cells, which functioned similarly as ferroptosis inhibitor Fer-1. In conclusion, BBR suppressed ferroptosis of islet ß cells via promoting GPX4 expression, providing new insights into the mechanism of BBR for islet ß cells.

Sini decoction ameliorates interrelated lung injury in septic mice by modulating the composition of gut microbiota.

Our work used cecal ligation and puncture (CLP) mice model and 16S rDNA sequencing to explore whether the therapeutic mechanism of Sini Decoction (SND) on sepsis was related to the intestinal flora currently of concern. Twenty-four hours after surgery, tissues and serum from three groups (Control, CLP and CLP + SND) were collected for further analysis and colon contents were isolated for 16S rDNA analysis. Mortality, histological examination and inflammatory cytokines levels confirmed that the sepsis model was induced successfully and resulted in serious pathological damage, while all of these could be reversed by SND. In intestinal flora analysis, the microbial richness and abundance were recovered after SND treatment. Furthermore, at the phylum level, the abundance of Proteobacteria showed drastic increase after CLP. Similarly, CLP surgery significantly disrupted the balance of intestinal flora, with a huge increase of Escherichia-Shigella, a Gram-negative genus that might release lipopolysaccharide (LPS) and other genera. And these shifts could be defused by SND, indicating its function of regulating gut microbiota. This study demonstrates that SND could ameliorate the symptoms and pathology associated with sepsis in CLP model via modulating the flora in intestinal tract, which enriches a possible mechanism of SND's therapeutic effect.

Hypoglycemic activity of CPU2206: A novel peptide from sika (Cervus nippon Temminck) antler.

Previous work had extracted and purified an antidiabetic peptide named CPU2206 with 7,127.6 Da. In this work, the toxicity of CPU2206 was first evaluated by daily administration to ICR mice, and after 28 days of administration, the body weight and lipid metabolism of the mice did not change significantly, which proved its safety and reliability. Second, further studies have focused on its hypoglycemic effects by daily intraperitoneal injection to alloxan-induced diabetic mice and KK-Ay mice, showing that CPU2206 effectively decreased the blood glucose and corresponding indicators of diabetic mice. Daily administration of CPU2206 nearly normalized the lipid metabolic parameters in diabetic mice. Histological examination also validated that CPU2206 ameliorated the pancreas injuries induced by alloxan or alleviated islet hypertrophy caused by insulin resistance in KK-Ay mice. To sum up, a totally new bioactive peptide CPU2206 obtained from sika antler showed significantly antidiabetic as well as lipid-lowering effects in diabetic mice. PRACTICAL APPLICATIONS: Antler has been used as a traditional Chinese medicine to invigorate primordial energy, enrich the blood, strengthen bones, and improve both male and female sexual functions for thousands of years. Traditionally, velvet antler can be grinded directly and taken orally, or used in porridge, wine and meat stew. Our experiment enriches the research on the function of edible antlers, provides the basis for developing it into functional health food, and on the other hand, provides an idea for finding new antidiabetic drugs.

Sini decoction ameliorates sepsis-induced acute lung injury via regulating ACE2-Ang (1-7)-Mas axis and inhibiting the MAPK signaling pathway.

Sepsis, as life-threatening organ dysfunction caused by a dysregulated host response to infection, is characterized by the extensive release of cytokines and other mediators. Sini decoction (SND), a traditional Chinese prescription medicine, has been used clinically for the treatment of sepsis. But its explicit mechanism of action is still unclear. The present study aims to evaluate the potential protective effects of SND on sepsis-induced acute lung injury (ALI). After SND intervention, the lung tissues of each experimental group were collected. H&E sections were used to observe the pathological changes of lung tissue, and alveolar lavage fluid was collected to detect the infiltration of inflammatory cells. Level of inflammatory factors in lung tissue were analyzed by qRT-PCR. The change of Renin angiotensin system (RAS), as well as downstream MAPK/NF-κB signaling pathways were measured by Western blot. For in vitro experiments, human umbilical vein endothelial cells (HUVECs) were pretreated with lipopolysaccharide (LPS) and treated with SND. Subsequently, the expression levels of RAS and MAPK/NF-κB signaling pathways were measured by Western blot. In vivo, we found that SND significantly attenuated sepsis-induced pathological injury in the lung. SND also inhibited LPS-mediated inflammatory cell infiltration, the expression of pro-apoptotic proteins and the production of IL-6, IL-1ß, TNF-α and MCP-1. In vitro, experiments using a co-culture of HUVECs with SND showed that there was a decrease in pro-apoptotic protein and pro-inflammatory mediator. In this research, we also found that SND protective action could be attributed to the regulation of renin-angiotensin system (RAS). MAPKs and NF-κB pathways. To conclude, our study demonstrated that SND ameliorates sepsis-induced-ALI via regulating ACE2-Ang (1-7)-Mas axis and inhibiting the MAPK signaling pathway.

Moxibustion improves ovary function by suppressing apoptosis events and upregulating antioxidant defenses in natural aging ovary.

AIMS: Ovarian aging is a natural physiological phenomenon accompanied by follicular atresia as well as the decline of oocyte quality. Moxibustion is a form of traditional Chinese medicine therapy which has been reported to treat many aging-related problems and improve immune defense. MATERIALS AND METHODS: Moxibustion treatment was applied to the 10-month female rats for 2 or 6 months to evaluate whether moxibustion could delay ovarian aging. The expression levels of NQO-1, HO-1, Bax and Bcl-2 were examined by Western blotting. The serum levels of E2 and FSH concentration were measured through ELISA. P21, P16, NQO-1, HO-1, Bax and Bcl-2 were measured by qRT-PCR. KEY FINDINGS: We demonstrated that moxibustion treatment could attenuate oxidative stress and apoptosis in ovaries, which lead to ovarian aging. The ovary histomorphology, serum FSH, E2 levels as well as aging markers P21 and P16 expression were compared among the groups, which showed that moxibustion treatment could alleviate the ovary fibrosis, decrease the aging markers expression and increase secretion of ovary functional hormones. The mRNA and protein expression levels of the antioxidative stress-related genes HO-1 and NQO-1 were increased after moxibustion treatment. The antiapoptotic factor Bcl-2 and proapoptotic factor Bax were also detected by qRT-PCR and western blotting, and the results demonstrated that moxibustion significantly downregulated the ratio of Bax/Bcl-2, suggesting that moxibustion could reduce apoptosis in the ovaries of aged rats. SIGNIFICANCE: In conclusion, our research revealed that moxibustion could improve ovary function by suppressing apoptosis events and upregulating antioxidant defenses in the natural aging ovary.