Grape Seed Proanthocyanidins Exert a Neuroprotective Effect by Regulating Microglial M1/M2 Polarisation in Rats with Spinal Cord Injury.

Spinal cord injury (SCI) is a highly disabling disorder for which few effective treatments are available. Grape seed proanthocyanidins (GSPs) are polyphenolic compounds with various biological activities. In our preliminary experiment, GSP promoted functional recovery in rats with SCI, but the mechanism remains unclear. Therefore, we explored the protective effects of GSP on SCI and its possible underlying mechanisms. We found that GSP promoted locomotor recovery, reduced neuronal apoptosis, increased neuronal preservation, and regulated microglial polarisation in vivo. We also performed in vitro studies to verify the effects of GSP on neuronal protection and microglial polarisation and their potential mechanisms. We found that GSP regulated microglial polarisation and inhibited apoptosis in PC12 cells induced by M1-BV2 cells through the Toll-like receptor 4- (TLR4-) mediated nuclear factor kappa B (NF-κB) and phosphatidylinositol 3-kinase/serine threonine kinase (PI3K/AKT) signaling pathways. This suggests that GSP regulates microglial polarisation and prevents neuronal apoptosis, possibly by the TLR4-mediated NF-κB and PI3K/AKT signaling pathways.

Natural Products of Pharmacology and Mechanisms in Nucleus Pulposus Cells and Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) is one of the main causes of low back pain (LBP), which severely reduces the quality of life and imposes a heavy financial burden on the families of affected individuals. Current research suggests that IDD is a complex cell-mediated process. Inflammation, oxidative stress, mitochondrial dysfunction, abnormal mechanical load, telomere shortening, DNA damage, and nutrient deprivation contribute to intervertebral disc cell senescence and changes in matrix metabolism, ultimately causing IDD. Natural products are widespread, structurally diverse, afford unique advantages, and exhibit great potential in terms of IDD treatment. In recent years, increasing numbers of natural ingredients have been shown to inhibit the degeneration of nucleus pulposus cells through various modes of action. Here, we review the pharmacological effects of natural products on nucleus pulposus cells and the mechanisms involved. An improved understanding of how natural products target signalling pathways will aid the development of anti-IDD drugs. This review focuses on potential IDD drugs.

YY1 deficiency in ß-cells leads to mitochondrial dysfunction and diabetes in mice.

BACKGROUND: The transcription factor YY1 is an important regulator for metabolic homeostasis. Activating mutations in YY1 lead to tumorigenesis of pancreatic ß-cells, however, the physiological functions of YY1 in ß-cells are still unknown. Here, we investigated the effects of YY1 ablation on insulin secretion and glucose metabolism. METHODS: We established two models of ß-cell-specific YY1 knockout mice. The glucose metabolic phenotypes, ß-cell mass and ß-cell functions were analyzed in the mouse models. Transmission electron microscopy was used to detect the ultrastructure of ß-cells. The flow cytometry analysis, measurement of OCR and ROS were performed to investigate the mitochondrial function. Histological analysis, quantitative PCR and ChIP were performed to analyze the target genes of YY1 in ß-cells. RESULTS: Our results showed that loss of YY1 resulted in reduction of insulin production, ß-cell mass and glucose tolerance in mice. Ablation of YY1 led to defective ATP production and mitochondrial ROS accumulation in pancreatic ß-cells. The inactivation of YY1 impaired the activity of mitochondrial oxidative phosphorylation, induced mitochondrial dysfunction and diabetes in mouse models. CONCLUSION: Our findings demonstrate that the transcriptional activity of YY1 is essential for the maintenance of mitochondrial functions and insulin secretion in ß-cells.

Effect of different extraction protocols on anticancer and antioxidant activities of Berberis koreana bark extracts.

High-pressure extraction and ultrasonification extraction techniques were employed to extract bioactive compounds from Berberis koreana. This study aimed to determine the effect of ultrasonification in a high pressure process on the extraction yield, and the anticancer and antioxidant activities of the B. koreana bark extract. The effect of high-pressure extraction time when carried out for 5 and 15 min (HP5 and HP15) was also investigated. The best extraction yield with maximum percentage of phenolic compounds was obtained using high pressure with sonification (HPWS) extraction method. Experimental results indicated that HPWS altered the antioxidant activities, including the scavenging capacity of diphenylpicrylhydrazyl (DPPH) and xanthine oxidase. HP5 and HP15 with conventional extraction have almost similar bioactivity, but showed lower antioxidant and anticancer activities compared to HPWS. The results showed that the application of ultrasonification improved the extraction efficiency for bioactive compounds and, as deduced from chromatographic profiles, it may have allowed the release of new compounds. The scanning electron microscope (SEM) showed evidence of rupturing of the tissue surface treated with HPWS, in contrast to conventional extraction, HP5, and HP15. The HPWS extraction was not only more efficient but also convenient for the recovery and purification of the active compounds of hard plant tissues.