Codonopsis pilosula water extract delays D-galactose-induced aging of the brain in mice by activating autophagy and regulating metabolism.
Codonopsis pilosula (C. pilosula), also called "Dangshen" in Chinese, is derived from the roots of Codonopsis pilosula (Franch.) Nannf. (C. pilosula), Codonopsis pilosula var. Modesta (Nannf.) L.D.Shen (C. pilosula var. modesta) or Codonopsis pilosula subsp. Tangshen (Oliv.) D.Y.Hong (C. pilosula subsp. tangshen), is a well-known traditional Chinese medicine. It has been regularly used for anti-aging, strengthening the spleen and tonifying the lungs, regulating blood sugar, lowering blood pressure, strengthening the body's immune system, etc. However, the mechanism, by which, C. pilosula exerts its therapeutic effects on brain aging remains unclear.
This study aimed to investigate the underlying mechanisms of the protective effects of C. pilosula water extract (CPWE) on the hippocampal tissue of D-galactose-induced aging mice.
In this research, plant taxonomy has been confirmed in the "The Plant List" database (www.theplantlist.org). First, an aging mouse model was established through the intraperitoneal injections of D-galactose solution, and low-, medium-, and high-dose CPWE were administered to mice by gavage for 42 days. Then, the learning and memory abilities of the mice were examined using the Morris water maze tests and step-down test. Hematoxylin and eosin staining was performed to visualize histopathological damage in the hippocampus. A transmission electron microscope was used to observe the ultrastructure of hippocampal neurons. Immunohistochemical staining was performed to examine the expression of glial fibrillary acidic protein (GFAP), the marker protein of astrocyte activation, and autophagy-related proteins, including microtubule-associated protein light chain 3 (LC3) and sequestosome 1 (SQSTM1)/p62, in the hippocampal tissues of mice. Moreover, targeted metabolomic analysis was performed to assess the changes in polar metabolites and short-chain fatty acids in the hippocampus.
First, CPWE alleviated cognitive impairment and ameliorated hippocampal tissue damage in aging mice. Furthermore, CPWE markedly alleviated mitochondrial damage, restored the number of autophagosomes, and activated autophagy in the hippocampal tissue of aging mice by increasing the expression of LC3 protein and reducing the expression of p62 protein. Meanwhile, the expression levels of the brain injury marker protein GFAP decreased. Moreover, quantitative targeted metabolomic analysis revealed that CPWE intervention reversed the abnormal levels of L-asparagine, L-glutamic acid, L-glutamine, serotonin hydrochloride, succinic acid, and acetic acid in the hippocampal tissue of aging mice. CPWE also significantly regulated pathways associated with D-glutamine and D-glutamate metabolism, nitrogen metabolism, arginine biosynthesis, alanine, aspartate, and glutamate metabolisms, and aminoacyl-tRNA biosynthesis.
CPWE could improve cognitive and pathological conditions induced by D-galactose in aging mice by activating autophagy and regulating metabolism, thereby slowing down brain aging.
Wang X
，Kang J
，Li X
，Wu P
，Huang Y
，Duan Y
，Feng J
，Wang J
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Effects of icariin on long noncoding RNA and mRNA expression profile in the aortas of apoE-deficient mice.
Objective : The beneficial effects of icariin (ICA) in ameliorating atherosclerosis (AS) are well known, but the underlying protective mechanism has not been fully elucidated. The present study aimed to investigate altered long noncosing RNA (lncRNA) and mRNA expression profiles in ApoE-/- mice after ICA treatment. Method : The atherosclerotic plaque area was evaluated on high-fat diet (HFD)-induced ApoE-/- mice treated with either ICA or vehicle. LncRNA and mRNA integrated microarrays was performed on aortic tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were utilized to explore the significant function and pathway of the differentially expressed (DE) mRNAs, global signal transduction network were constructed to select key mRNAs, and lncRNA-mRNA co-expression network was built to find out the interactions between lncRNA and mRNA. Quantitative real-time PCR (qPCR) was used to further validate the expressions of selected lncRNAs and mRNAs. Results : Administration of ICA significantly reduced plaque size after 12 weeks (P<0.05). A total of 1512 DE lncRNAs and 2059 DE mRNAs were identified. The mRNAs: protein kinase C, β (Prkcb), Cyp2c65, Mapk10, Calmodulin 5 (Calm5), Calmodulin-like 3 (Calml3) and Camk4 were selected as hub mRNAs, the correlated lncRNAs in co-expression network were identified as important regulatory lncRNAs. The identified target pairs such as lncRNA-NONMMUT000659/Prkcb may play critical roles in AS development mediated by ICA. Conclusion : Taken together, our study highlights a panel of DE lncRNAs and mRNAs that could explain the molecular mechanism of ICA's anti-atherosclerotic effects. The work lays a foundation for subsequent genes functional researches, which could contribute to provide new therapeutic targets for AS.
Zhang Y
，Xu R
，Li X
，Tan Q
，Huang P
，Zhang Y
，Qin M
，Ren L
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ResearchGate
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钛学术
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