Although astragaloside IV, a saponin isolated from Astragalus membranaceus, has been shown to protect the myocardium against ischemia/reperfusion injury, its effect on the status of sarcoplasmic reticulum (SR) Ca²⁺ transport in the injured myocardium remains largely unknown. In this study, we investigated whether in cultured cardiomyocytes subjected to hypoxia and reoxygenation (H/R) administration of astragaloside IV during H/R attenuates the myocardial cell injury and prevents changes in Ca²⁺ handling activities and gene expression of SR Ca²⁺ pump. Cultured cardiomyocytes from neonatal rats were exposed to 6 h of hypoxia followed by 3 h of reoxygenation. Myocyte injury was determined by the release of cardiac troponin I in supernatant. Astragaloside IV significantly inhibited cardiac troponin I release after H/R in a dose-dependent manner. The diastolic [Ca²⁺]_i measured with Fura-2/AM was significantly increased after reoxygenation. Astragaloside IV prevented the rise of diastolic [Ca²⁺]_i and the depression of caffeine-induced Ca²⁺ transients caused by H/R. Furthermore, the observed depressions in SR Ca²⁺-ATPase activity as well as the mRNA and protein expression of SR Ca²⁺-ATPase in hypoxic-reoxygenated cardiomyocytes were attenuated by astragaloside IV treatment. These results suggest that the beneficial effect of astragaloside IV in H/R-induced injury may be related to normalization of SR Ca²⁺ pump expression and, thus, may prevent the depression in SR Ca²⁺ handling.

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Osteoarthritis (OA) is characterized by a loss of articular cartilage accompanied with inflammation of synovium. β-Ecdysterone (Ecd), a major component of several Chinese herbal medicines, e.g., Achyranthes bidentata BL., has been used for the prevention and treatment of OA. Ecd is an estrogen analog and is likely to have similar pharmacological effects including the effect of protective chondrocytes. This study investigated the effects of Ecd on interleukin-1β (IL-1β)-induced apoptosis and inflammation in rat chondrocytes. Ecd protected chondrocytes from IL-1β-induced injury by inhibiting expression of Bax, p53 phosphorylation, and promoting expression of Bcl-xL . Simultaneously, Ecd reduced caspase 3 activity. IL-1β-induced inflammation and matrix degration were also prevented by Ecd via down-regulation of matrix metalloproteinases MMP 3, MMP 9, and cyclooxygenase-2 expression. Additionally, Ecd inhibited Nuclear Factor Kappa B (NF-κB) p65 phosphorylation, IκBα degradation, and phosphorylation in IL-1β-induced rat chondrocytes. These results suggested Ecd exerted anti-apoptosis and anti-inflammation in IL-1β-induced rat chondrocytes, which might be related to NF-κB signal pathway.

Saponins, an important group of bioactive plant natural products, are glycosides of triterpenoid or steroidal aglycones. Their diverse biological activities are ascribed to their different structures. Saponins have long been recognized as key ingredients in traditional Chinese medicine. Accumulated evidence suggests that saponins have significant neuroprotective effects on attenuation of central nervous system disorders, such as stroke, Alzheimer's disease, Parkinson's disease, and Huntington's disease. However, our understanding of the mechanisms underlying the observed effects remains incomplete. Based on recently reported data from basic and clinical studies, this review highlights the proposed mechanisms of their neuroprotective function including antioxidant, modulation of neurotransmitters, anti-apoptosis, anti-inflammation, attenuating Ca(2+) influx, modulating neurotrophic factors, inhibiting tau phosphorylation, and regeneration of neural networks.

Inflammation is a potent promoter of tumor metastasis. The aim of the present study was to explore the function of systemic inflammation in the formation of lung metastasis of breast cancer cells in a mouse model. BALB/c mice were injected intraperitoneally with lipopolysaccharide (LPS) in order to establish an inflammatory animal model and 4T1 murine breast cancer cells were injected through the tail vein to induce lung metastasis. The levels of proinflammatory cytokines were evaluated by ELISA. Metastases on the surface of the lungs were counted and histologically analyzed by hematoxylin and eosin staining. Angiogenesis in the lungs was examined by CD31 immunofluorescence. Mouse pulmonary endothelial cells (MPVECs) were isolated and used to assay endothelial tube formation and determine the protein expression levels of vascular endothelial growth factor (VEGF) in vitro. Serum levels of VEGF and prostaglandin E2 (PGE2), the number and size of metastatic lesions, and the expression levels of cyclooxygenase‑2 were significantly greater in the lungs of LPS‑treated mice, as compared with those in control mice threated with phosphate‑buffered saline. Blood vessel density was also markedly increased in the LPS‑treated mice. These increases were reversed by treatment with celecoxib. In vitro, the protein expression levels of VEGF produced by the PGE2‑treated cells were significantly increased in a concentration‑dependent manner. In addition, the production of VEGF was increased in response to treatment with the PGE2 receptor (EP2) agonist ONO‑AE1‑259‑01; however, this increase was abrogated by treatment with AH6809, an EP2 receptor antagonist. Treatment with PGE2 or VEGF alone promoted the tube formation of MPVECs and this effect was reversed by treatment with celecoxib. These results demonstrated that PGE2 may regulate the release of VEGF by MPVECs through the EP2 receptor pathway and thereby promoted pulmonary angiogenesis and breast cancer metastasis in a mouse model.

Mild cognitive impairment (MCI) is often considered a critical time window for predicting early conversion to Alzheimer's disease (AD). Brain functional connectome data (i.e., functional connections, global and nodal graph metrics) based on resting-state functional magnetic resonance imaging (rs-fMRI) provides numerous information about brain networks and has been used to discriminate normal controls (NCs) from subjects with MCI. In this paper, Student's t-tests and group-least absolute shrinkage and selection operator (group-LASSO) were used to extract functional connections with significant differences and the most discriminative network nodes, respectively. Based on group-LASSO, the middle temporal, inferior temporal, lingual, posterior cingulate, and middle frontal gyri were the most predominant brain regions for nodal observation in MCI patients. Nodal graph metrics (within-module degree, participation coefficient, and degree centrality) showed the maximum discriminative ability. To effectively combine the multipattern information, we employed the multiple kernel learning support vector machine (MKL-SVM). Combined with functional connectome information, the MKL-SVM achieved a good classification performance (area under the receiving operating characteristic curve = 0.9728). Additionally, the altered brain connectome pattern revealed that functional connectivity was generally decreased in the whole-brain network, whereas graph theory topological attributes of some special nodes in the brain network were increased in MCI patients. Our findings demonstrate that optimal feature selection and combination of all connectome features (i.e., functional connections, global and nodal graph metrics) can achieve good performance in discriminating NCs from MCI subjects. Thus, the combination of functional connections and global and nodal graph metrics of brain networks can predict the occurrence of MCI and contribute to the early clinical diagnosis of AD.

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