Chinese herbal compound Jinsiwei improves synaptic plasticity in mice with sporadic Alzheimer's disease induced by streptozotocin.

OBJECTIVE: To investigate the efficacy of Jinsiwei (a patented Chinese herbal compound) on learning and memory impairment, the number of synapses and synaptic plasticity-related structural and functional protein expression in mice with sporadic Alzheimer's disease (SAD) induced by streptozotocin. METHODS: Seventy-five C57/BL6J male mice were intracerebroventricularly injected with streptozotocin to establish the animal model of SAD. Mice were randomly divided into the model group (MG), donepezil group (DG), and the Jinsiwei high, medium, and low-dose groups (JH, JM, JL). Another fifteen C57/BL6J male mice were injected with artificial cerebrospinal fluid as the control group (CG). The intervention groups were intragastrically administrated with corresponding medicine, while the CG and MG were given 0.5% carboxymethyl cellulose by gavage. After 3 months, the Morris Water Maze test and step-down passive avoidance test were used to assess the learning and memory ability of mice. Synapses in hippocampal CA1 were observed by transmission electron microscope. Immunohistochemistry and western blotting were used to assess the distribution and expression levels of synaptic plasticity-related structural and functional proteins involving drebrin, cofilin, synapsin (syn), and N-methyl D-aspartate receptor subtype 2B (NR2B). RESULTS: The Morris Water Maze results showed that the escape latency in the Jinsiwei intervention groups was significantly shorter than that of the MG. Results of the step-down passive-avoidance test showed that the error times in the Jinsiwei intervention groups were significantly reduced compared with the MG. Transmission electron microscope results showed that the number of synapses in hippocampal CA1 was obviously increased in the Jinsiwei intervention groups compared with the MG. Immunohistochemical and western blotting results revealed that the positive cells and expression levels of drebrin, syn, and NR2B were significantly decreased in the MG and meanwhile cofilin significantly increased, while these changes were reversed after the Jinsiwei treatment. CONCLUSIONS: Jinsiwei can alleviate learning and memory impairments in a mouse model of SAD, increase the number of synapses and enhance synaptic plasticity rescuing the expression of drebrin, syn, and NR2B and inhibiting cofilin expression.

Effect of Baofeikang Granules on PI3K/Akt Signaling Pathway in Pulmonary Fibrosis： Prediction Based on Network Pharmacology and Verification Based on Animal Experiment / 中国实验方剂学杂志

ObjectiveTo investigate the targets and mechanism of Baofeikang granules in the treatment of pulmonary fibrosis based on network pharmacology and verify the predicted mechanism based on animal experiment. MethodThe active ingredients and targets of Baofeikang granules were screened via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform， and the targets of pulmonary fibrosis were searched in various disease databases. The common targets shared by Baofeikang granules and the disease were extracted for the establishment of the protein-protein interaction （PPI） network in STRING. Cytoscape 3.8.0 was used to analyze the network topology of the key targets and to establish the ''active ingredient-target'' network. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were performed on the core targets to explore their possible molecular mechanisms. The rats were assigned into four groups： normal group， model group， prednisone acetate group， and Baofeikang granules group. The rat model of interstitial lung fibrosis was established by tracheal instillation of bleomycin. After 21 days of gavage， the lung tissues of rats were stained with hemotoxylin and eosin （HE） for the observation of morphological changes， and phosphatidylinositol 3-kinase （PI3K） and protein kinase B （Akt） were detected via immunohistochemical （IHC） staining. ResultBased on network pharmacology， 18 key targets of Baofeikang granules were identified for the treatment of pulmonary interstitial fibrosis， including Akt1， mitogen-activated protein kinase （MAPK） 1， myelocytomatosis oncogene （MYC）， hypoxia-inducible factor-1α （HIF-1α）， cyclin-dependent kinase inhibitor 1A （CDKN1A）， epidermal growth factor receptor （EGFR）， and Runt-related transcription factor （RUNX2）. KEGG pathway enrichment predicted that Baofeikang granules exerted anti-fibrotic effect mainly through PI3K/Akt， tumor necrosis factor （TNF）， and interleukin-17 （IL-17） signaling pathways. The IHC results in animal experiment showed that the protein levels of PI3K and Akt were lower in the Baofeikang granules group than in the model group （P<0.05， P<0.01）. ConclusionBaofeikang granules has low toxicity， multiple targets， and multiple pathways in the treatment of pulmonary fibrosis. It may alleviate pulmonary fibrosis through regulating PI3K/Akt signaling pathway， so as to improve the lung function.

Effect of Baofeikang Granules on PI3K/Akt Signaling Pathway in Pulmonary Fibrosis： Prediction Based on Network Pharmacology and Verification Based on Animal Experiment / 中国实验方剂学杂志

ObjectiveTo investigate the targets and mechanism of Baofeikang granules in the treatment of pulmonary fibrosis based on network pharmacology and verify the predicted mechanism based on animal experiment. MethodThe active ingredients and targets of Baofeikang granules were screened via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform， and the targets of pulmonary fibrosis were searched in various disease databases. The common targets shared by Baofeikang granules and the disease were extracted for the establishment of the protein-protein interaction （PPI） network in STRING. Cytoscape 3.8.0 was used to analyze the network topology of the key targets and to establish the ''active ingredient-target'' network. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were performed on the core targets to explore their possible molecular mechanisms. The rats were assigned into four groups： normal group， model group， prednisone acetate group， and Baofeikang granules group. The rat model of interstitial lung fibrosis was established by tracheal instillation of bleomycin. After 21 days of gavage， the lung tissues of rats were stained with hemotoxylin and eosin （HE） for the observation of morphological changes， and phosphatidylinositol 3-kinase （PI3K） and protein kinase B （Akt） were detected via immunohistochemical （IHC） staining. ResultBased on network pharmacology， 18 key targets of Baofeikang granules were identified for the treatment of pulmonary interstitial fibrosis， including Akt1， mitogen-activated protein kinase （MAPK） 1， myelocytomatosis oncogene （MYC）， hypoxia-inducible factor-1α （HIF-1α）， cyclin-dependent kinase inhibitor 1A （CDKN1A）， epidermal growth factor receptor （EGFR）， and Runt-related transcription factor （RUNX2）. KEGG pathway enrichment predicted that Baofeikang granules exerted anti-fibrotic effect mainly through PI3K/Akt， tumor necrosis factor （TNF）， and interleukin-17 （IL-17） signaling pathways. The IHC results in animal experiment showed that the protein levels of PI3K and Akt were lower in the Baofeikang granules group than in the model group （P<0.05， P<0.01）. ConclusionBaofeikang granules has low toxicity， multiple targets， and multiple pathways in the treatment of pulmonary fibrosis. It may alleviate pulmonary fibrosis through regulating PI3K/Akt signaling pathway， so as to improve the lung function.