Protective Effect of Astragaloside IV against Cadmium-Induced Damage on Mouse Renal Podocytes (MPC5).

In this study, we investigated the protective effect of Astragaloside IV (Ast) on mouse podocytes and its possible mechanism of action by constructing a cadmium-induced mouse renal podocytes model. We investigated the effects of cadmium (Cd) toxicity on cell number, morphology, the mitochondrial status of subcellular organelles, protein and gene levels, and the protective effects of Ast by constructing a model of Cd-induced damage to mouse renal podocytes (MPC5) and giving Ast protection at the same time. The results showed that exposure of MPC5 cells to CdCl2 culture medium containing 6.25 µM concentration acted with low cell mortality, but the mortality of MPC5 cells increased with the prolongation of cadmium exposure time. Given Ast, the death rate in the low dose group (12.5 µM) was significantly reduced, while the death rate in the medium dose group (25 µM) was extremely significantly reduced. In comparison to the control group, the Cd-exposed group exhibited a significant increase of 166.7% in malondialdehyde (MDA) content and a significant decrease of 17.1% in SOD activity. The mitochondrial membrane potential was also reduced to varying degrees. However, in the Ast-protected group compared to the Cd-exposed group, the MDA content significantly decreased by 20.8%, the SOD activity decreased by 7.14%, and the mitochondrial membrane potential showed a significant increase. Fluorescence staining of mitochondrial membrane potential indicated that Cd exposure caused mitochondrial apoptosis. In the 12-h cadmium-exposed group, the protein expression of Nephrin in mice significantly decreased by 33.4%. However, the expression of the Desmin protein significantly increased by 67.8%, and the expression of the autophagy protein LC3-II significantly increased by 55.5%. Meanwhile, the expression of PINK1, a mitochondrial autophagy pathway protein, was significantly increased in the 12 h and 24 h cadmium exposure groups. The mRNA level of PINK1 was significantly increased, and that of Parkin was decreased in the 48 h cadmium exposure group. Compared to the Cd-exposed group, the Ast group showed more significant improvements in the expression of podocyte structure, functional proteins, and mitochondrial autophagy pathway proteins. The immunological assay of mitochondrial autophagic pathway proteins further indicated that Cd-induced damage to MPC5 cells might be associated with the dysregulation of mitochondrial autophagy.

Hypoglycemic effect of astragaloside IV via modulating gut microbiota and regulating AMPK/SIRT1 and PI3K/AKT pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Astragali, the dried root of Astragalus mongholicus Bunge, has long been used in traditional Chinese Medicine to treat diabetes. Astragaloside IV (AS-IV), one of the most active ingredients in the root, has been shown to have anti-diabetes ability; however, its underlying mechanism is still unclear. MATERIALS AND METHODS: In this study, we evaluated the hypoglycemic effect and possible mechanisms of AS-IV in diabetic mice and insulin resistance-HepG2 cells. The components of the intestinal microflora in mice with type 2 diabetes mellitus (T2DM) were determined using high-throughput 16S rRNA gene sequencing. Moreover, the molecular mechanisms of specific members of insulin signaling pathways were analyzed. RESULTS: AS-IV significantly reversed the abnormalities in blood lipids, glucose, insulin resistance, as well as oxidative stress levels in T2DM mice. Histological finding showed that AS-IV could protect the cellular architecture of the liver and pancreas. AS-IV also regulated the abundance and diversity of intestinal flora of T2DM mice in a positive direction and increased butyric acid levels. The active role of AS-IV as an anti-diabetic compound by regulating the AMPK/SIRT1 and PI3K/AKT signaling pathways was revealed using a T2DM model and verified through the intervention of inhibitors using insulin-resistance HepG2 cells. CONCLUSION: Our results suggested that AS-IV may be used as an anti-diabetic drug candidate owing to its effects of regulating gut microbiota and AMPK/SIRT1 and PI3K/AKT signaling pathways.

Highly Sensitive Strain Sensor Based on a Stretchable and Conductive Poly(vinyl alcohol)/Phytic Acid/NH2-POSS Hydrogel with a 3D Microporous Structure.

Conductive hydrogel-based wearable strain sensors with tough, stretchable, self-recoverable, and highly sensitive properties are highly demanded for applications in electronic skin and human-machine interface. However, currently, hydrogel-based strain sensors put forward higher requirements on their biocompatibility, mechanical strength, and sensitivity. Herein, we report a poly(vinyl alcohol)/phytic acid/amino-polyhedral oligomeric silsesquioxane (PVA/PA/NH2-POSS) conductive composite hydrogel prepared via a facile freeze-thaw cycle method. Within this hydrogel, PA acts as a cross-linking agent and ionizes hydrogen ions to endow the material with ionic conductivity, while NH2-POSS acts as a second cross-linking agent by increasing the cross-linking density of the three-dimensional network structure. The effect of the content of NH2-POSS is investigated, and the composite hydrogel with 2 wt % NH2-POSS displays a uniform and dense three-dimensional (3D) network microporous structure, high conductivity of 2.41 S/m, and tensile strength and elongation at break of 361 kPa and 363%, respectively. This hydrogel is biocompatible and has demonstrated the application as a strain sensor monitoring different human movements. The assembled sensor is stretchable, self-recoverable, and highly sensitive with fast response time (220 ms) and excellent sensitivity (GF = 3.44).