Ginsenoside compound K ameliorates Alzheimer's disease in HT22 cells by adjusting energy metabolism.

Energy metabolism disorders have been shown to exert detrimental effects on the pathology of Alzheimer's disease (AD). The ginsenoside compound K (CK), a major intestinal metabolite underlying the pharmacological actions of orally administered ginseng, has an ameliorating effect against AD, but the relevant molecular mechanism remains unclear. We hypothesized that the improvement of AD by CK is mediated by the energy metabolism signaling pathway induced by amyloid ß peptide (Aß) and tested this hypothesis in HT22 cells. HT22 cells were incubated with CK and exposed to Aß. Cell viability was analyzed using the MTT assay. Cell growth curves were derived from real-time cell analysis. Apoptosis was determined by flow cytometry, Aß localization and expression by immunofluorescence, and ATP content by a specific assay kit. The expression of proteins related to the energy metabolism signaling pathway was analyzed using Western blotting. CK treatment improved cell viability, cell growth, and apoptosis induced by Aß, and the cellular localization and expression of Aß. Moreover, CK increased ATP content by promoting the activity of glucose transporters (GLUTs). Therefore, the neuroprotective effect of CK against Aß injury was mainly realized through the activation of the energy metabolism signaling pathway. CK treatment inhibits neuronal damage caused by Aß through the activation of the energy metabolism signaling pathway, revealing that CK might be one of the key bioactive ingredients of ginseng in the treatment of Alzheimer's disease and may serve as a preventive or therapeutic agent for Alzheimer's disease.

Oviductus Ranae protein hydrolyzate prevents menopausal osteoporosis by regulating TGFß/BMP2 signaling.

PURPOSE: It is known that menopausal osteoporosis (MOP) is the most typical form of osteoporosis, which is characterized by low bone mass and microstructure damage of the bone tissue, leading to increased bone fragility and risk of fracture. This study aimed to evaluate the protective effects of Oviductus Ranae protein hydrolyzate (ORPH) on the MOP in vivo. METHODS: Osteoporosis model was induced by ovariectomy, treated with ORPH 150 or 75 mg kg-1. Body weight and bone mineral density (BMD) of rats were measured at the beginning and the end of the experiment, and femoral maximum load was determined immediately after killing. The expression levels of alkaline phosphatase (ALP), Smad4, tartrate acid phosphatase (TRAP), BMP2, Runx2, CPB, ColI and osteocalcin were examined by RT-PCR or western-blotting. HE staining was used to observe the pathological changes in the femurs. Immunohistochemistry was used to detect the expression of ALP and BMP2. All data were analyzed by SPSS 13.0. RESULTS: The results revealed that ORPH had no effect on the weight of normal and osteoporotic rats. ORPH could significantly improve the femur BMD and increase the maximum load of the osteoporotic rats. ORPH could significantly upregulate the expression level of bone formation makers, ALP, osteocalcin, ColI, and Runx2, and downregulate the expression level of bone resorption marker, TRAP. In the ORPH group, the expression levels of BMP2, Smad4, and CPB of key proteins in the TGFß/BMP2 signaling pathway were significantly upregulated. In addition, immunohistochemistry showed that ALP and BMP2 expression in femurs of the ORPH group was stranger. H&E staining showed that ORPH (150 mg kg-1) significantly increased the thickness of trabeculae and decreased fracture risk. CONCLUSION: Collectively, ORPH plays a role in the prevention and treatment of osteoporosis, which may be a potential anti-osteoporosis drug.

Ginsenoside Compound K Regulates Amyloid ß via the Nrf2/Keap1 Signaling Pathway in Mice with Scopolamine Hydrobromide-Induced Memory Impairments.

The objective of this study was to investigate the neuroprotective and antioxidant effects of ginsenoside compound K (CK) in a model of scopolamine hydrobromide-induced, memory-impaired mice. The role of CK in the regulation of amyloid ß (Aß) and its capacity to activate the Nrf2/Keap1 signaling pathway were also studied due to their translational relevance to Alzheimer's disease. The Morris water maze was used to assess spatial memory functions. Levels of superoxide dismutase, glutathione peroxidase, and malondialdehyde in brain tissues were tested. Cell morphology was detected by hematoxylin and eosin staining and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling assay. Immunohistochemistry and western blotting were used to determine expression levels of Nrf2/Keap1 signaling pathway-related factors and Aß. Ginsenoside CK was found to enhance memory function, normalize neuronal morphology, decrease neuronal apoptosis, increase superoxide dismutase and glutathione peroxidase levels, reduce malondialdehyde levels, inhibit Aß expression, and activate the Nrf2/Keap1 signaling pathway in scopolamine-exposed animals. Based on these results, we conclude that CK may improve memory function in scopolamine-injured mice by regulating Aß aggregation and promoting the transduction of the Nrf2/Keap1 signaling pathway, thereby reducing oxidative damage to neurons and inhibiting neuronal apoptosis. This study suggests that CK may serve as a future preventative agent or treatment for Alzheimer's disease.

Genetic, epigenetic, and HPLC fingerprint differentiation between natural and ex situ populations of Rhodiola sachalinensis from Changbai Mountain, China.

Rhodiola sachalinensis is an endangered species with important medicinal value. We used inter-simple sequence repeat (ISSR) and methylation-sensitive amplified polymorphism (MSAP) markers to analyze genetic and epigenetic differentiation in different populations of R. sachalinensis, including three natural populations and an ex situ population. Chromatographic fingerprint was used to reveal HPLC fingerprint differentiation. According to our results, the ex situ population of R. sachalinensis has higher level genetic diversity and greater HPLC fingerprint variation than natural populations, but shows lower epigenetic diversity. Most genetic variation (54.88%) was found to be distributed within populations, and epigenetic variation was primarily distributed among populations (63.87%). UPGMA cluster analysis of ISSR and MSAP data showed identical results, with individuals from each given population grouping together. The results of UPGMA cluster analysis of HPLC fingerprint patterns was significantly different from results obtained from ISSR and MSAP data. Correlation analysis revealed close relationships among altitude, genetic structure, epigenetic structure, and HPLC fingerprint patterns (R2 = 0.98 for genetic and epigenetic distance; R2 = 0.90 for DNA methylation level and altitude; R2 = -0.95 for HPLC fingerprint and altitude). Taken together, our results indicate that ex situ population of R. sachalinensis show significantly different genetic and epigenetic population structures and HPLC fingerprint patterns. Along with other potential explanations, these findings suggest that the ex situ environmental factors caused by different altitude play an important role in keeping hereditary characteristic of R. sachalinensis.

Combination of doxorubicin-based chemotherapy and polyethylenimine/p53 gene therapy for the treatment of lung cancer using porous PLGA microparticles.

In this study, porous PLGA microparticles for the co-delivery of doxorubicin and PEI25K/p53 were successfully prepared by the water-oil-water emulsion solvent evaporation method, using ammonium bicarbonate as a porogen. The porous microparticles were obtained with a mean diameter of 22.9±11.8µm as determined by laser scattering particle size analysis. The particles' surface porous morphology and distributions of doxorubicin and p53 were systematically characterized by scanning electron microscopy, flow cytometry, fluorescence microscopy and confocal laser scanning microscopy, revealing that doxorubicin and the plasmid were successfully co-encapsulated. Encapsulation efficiencies of 88.2±1.7% and 36.5±7.5% were achieved for doxorubicin and the plasmid, respectively, demonstrating that the porous structure did not adversely affect payload encapsulation. Microparticles harboring both doxorubicin and PEI25K/p53 exhibited enhanced tumor growth inhibition and apoptosis induction compared to those loaded with either agent alone in A549 human lung adenocarcinoma cells. Overall, the porous PLGA microparticles provide a promising anticancer delivery system for combined chemotherapy and gene therapy, and have great potential as a tool for sustained local drug delivery by inhalation.