Panax notoginseng saponins protect PC12 cells against Aβ induced injury via promoting parkin-mediated mitophagy. 2022

Yixuan Jiang, and Hemei Li, and Panling Huang, and Shanliang Li, and Bocun Li, and Lini Huo, and Jing Zhong, and Ziyu Pan, and Yuqing Li, and Xing Xia
School of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530200, PR China.

BACKGROUND Panax notoginseng (Burk) F. H. Chen is a well-known traditional Chinese medicine with a long history and is widely used in the treatment of cerebrovascular disease. Panax notoginseng saponins (PNS) are the main active ingredients in Panax notoginseng (Burk) F. H. Chen, and its injection is used to treat nerve damage caused by cerebral ischemia and other conditions. PNS is thought to alleviate cognitive impairment in patients with Alzheimer's disease; however, its mechanism of action is unclear. OBJECTIVE We elucidated the role of PNS in attenuating cellular mitochondrial damage caused by amyloid β (Aβ) protein and in protecting cell viability from the perspective of regulating autophagy. By investigating the effects of PNS on the targets regulating mitophagy, we wanted to reveal the autophagy related mechanism by which PNS attenuated Aβ damage in neuronal cells. METHODS The effect of PNS on the mitochondrial membrane potential of Aβ-injured PC12 cells was detected using flow cytometry, which reflected the alleviating effect of PNS on mitochondrial damage. Using mRFP-GFP-LC3-transfected PC12 cells, the effect of PNS on cellular autophagy flux was observed using laser confocal microscopy. Formation of the intracellular autophagosome was observed using transmission electron microscopy, which reflected the activation of autophagy by PNS. The siPINK1 lentivirus was used to silence the PINK1 gene in PC12 cells to obtain siPINK1-PC12 cells. The effects of PNS on the expression of the PINK1 gene and on the autophagy-related proteins LC3II/Ⅰ, p62, PINK1, parkin, NDP52, and OPTN were observed to reveal the possible targets of PNS in regulating autophagy. RESULTS After PNS treatment, the viability of Aβ-injured PC12 cells improved and the mitochondrial membrane potential was restored. PNS treatment significantly enhanced the autophagy flux of damaged cells and increased the levels of LC3II/Ⅰ protein and decreased p62 protein, while significantly improving the structure and mitochondrial morphology of PC12 cells injured by Aβ. These changes led to more autophagosomes wrapping around the damaged mitochondria and promoting the depletion of OPTN, a mitophagy receptor. After silencing the PINK1 gene, PNS could not alter the PINK1 gene and protein levels, but could still increase LC3II/Ⅰ, decrease p62 and OPTN, and significantly increase the amount of parkin. CONCLUSIONS PNS could enhance the autophagic activity of cells, alleviate mitochondrial damage caused by Aβ injury, and protect the activity of PC12 cells. It is possible that enhanced autophagy was achieved by promoting the recruitment of parkin protein to the mitochondrial receptors in a non-PINK1-dependent manner.

UI MeSH Term Description Entries
D008517 Phytotherapy Use of plants or herbs to treat diseases or to alleviate pain. Herb Therapy,Herbal Therapy
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001343 Autophagy The segregation and degradation of various cytoplasmic constituents via engulfment by MULTIVESICULAR BODIES; VACUOLES; or AUTOPHAGOSOMES and their digestion by LYSOSOMES. It plays an important role in BIOLOGICAL METAMORPHOSIS and in the removal of bone by OSTEOCLASTS. Defective autophagy is associated with various diseases, including NEURODEGENERATIVE DISEASES and cancer. Autophagocytosis,ER-Phagy,Lipophagy,Nucleophagy,Reticulophagy,Ribophagy,Autophagy, Cellular,Cellular Autophagy,ER Phagy
D012503 Saponins A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycone moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Saponin
D016229 Amyloid beta-Peptides Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue. Alzheimer beta-Protein,Amyloid Protein A4,Amyloid beta-Peptide,Amyloid beta-Protein,beta Amyloid,beta-Amyloid Protein,Alzheimer's ABP,Alzheimer's Amyloid Fibril Protein,Amyloid AD-AP,Amyloid Fibril Protein, Alzheimer's,Amyloid beta-Proteins,ABP, Alzheimer's,AD-AP, Amyloid,Alzheimer ABP,Alzheimer beta Protein,Alzheimers ABP,Amyloid AD AP,Amyloid beta Peptide,Amyloid beta Peptides,Amyloid beta Protein,Amyloid beta Proteins,Amyloid, beta,Protein A4, Amyloid,Protein, beta-Amyloid,beta Amyloid Protein,beta-Peptide, Amyloid,beta-Peptides, Amyloid,beta-Protein, Alzheimer,beta-Protein, Amyloid,beta-Proteins, Amyloid
D016716 PC12 Cells A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation. Pheochromocytoma Cell Line,Cell Line, Pheochromocytoma,Cell Lines, Pheochromocytoma,PC12 Cell,Pheochromocytoma Cell Lines
D044767 Ubiquitin-Protein Ligases A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes. Ubiquitin-Protein Ligase,E3 Ligase,E3 Ubiquitin Ligase,Ubiquitin Ligase E3,Ubiquitin-Protein Ligase E3,Ligase E3, Ubiquitin,Ligase E3, Ubiquitin-Protein,Ligase, E3,Ligase, E3 Ubiquitin,Ligase, Ubiquitin-Protein,Ligases, Ubiquitin-Protein,Ubiquitin Ligase, E3,Ubiquitin Protein Ligase,Ubiquitin Protein Ligase E3,Ubiquitin Protein Ligases
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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