Neuroprotective Effect of Danggui Shaoyao San via the Mitophagy-Apoptosis Pathway in a Rat Model of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a serious neurodegenerative disease. While the main pathological characteristic of AD is widely believed to be the accumulation of amyloid-beta (Aβ) in neurons around neurofibrillary plaques, the molecular mechanism of pathological changes is not clear. Traditional Chinese medicine offers many treatments for AD. Among these, Danggui Shaoyao San (DSS) is a classic prescription. In this study, an AD model was established by injecting Aβ 1–42 into the brains of rats, which were then treated with different concentrations of Danggui Shaoyao San (sham operation; model; and Danggui Shaoyao San high-dose, medium-dose, and low-dose intervention groups). The Morris water maze test was used to assess the learning and memory abilities of the animals in each group. Nissl staining was used to detect neurons. Mitophagy was evaluated by transmission electron microscopy and immunofluorescence colocalization. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expression levels of autophagy- and apoptosis-related proteins were measured by western blot. Compared to the model group, the groups of AD rats administered medium and high doses of Danggui Shaoyao San showed significantly increased learning and memory abilities ( P < 0.05 ), as well as significantly increased autophagosomes in the hippocampus. Moreover, the expression of PTEN-induced kinase 1 (PINK1), Parkin, and microtubule-associated protein light chain 3 (LC3-I/LC3-II) was increased, while that of p62 was significantly decreased ( P < 0.05 ). The neuronal apoptosis rate was also significantly decreased, the Bcl-2/Bax ratio was significantly increased, and the cleaved caspase-3 protein expression was significantly decreased ( P < 0.05 ). Therefore, Danggui Shaoyao San inhibited neuronal apoptosis in AD rats via a mechanism that may be related to the activation of the PINK1-Parkin-mediated mitophagy signaling pathway.

Identification of tryptophan metabolism-related genes in immunity and immunotherapy in Alzheimer’s disease

“…The paraffin-embedded tissue blocks were then sectioned into 4 μm thick slices using a paraffin microtome (HM355S, Thermo Scientific, Shanghai, China). To prepare the tissue for immunostaining, the sections underwent steps including deparaffinization, antigen retrieval, blocking, and incubation with primary and secondary antibodies, as described in previous studies [ 15 ]. Specifically, cell transparency techniques were employed, and antigen retrieval was performed to enhance the antigenicity of the tissue.…”

Intestinal flora study reveals the mechanism of Danggui Shaoyao San and its decomposed recipes to improve cognitive dysfunction in the rat model of Alzheimer’s disease

“…The model group received an equivalent amount of saline by oral gavage. The dosages for the Danggui Shaoyao San group and the decoction groups were calculated based on the original formula of Danggui Shaoyao San (24 g•kg -1 •d -1 ) and adjusted according to the body surface area and previous preliminary studies (Yang et al, 2023).…”

Medicine–food herb:Angelica sinensis, a potential therapeutic hope for Alzheimer's disease and related complications

“…By using a network pharmacology approach, Song Zhenyan investigated the mechanisms of action of DSS in the treatment of AD at the systemic network level and found that the active compounds of DSS interacted with multiple targets and multiple pathways in a synergistic manner, mainly through anti-inflammatory, anti-apoptotic, metabolic enhancement and immune system enhancement pathways to exert important therapeutic effects on AD. 60 Studies have found that DDS could ameliorate the amyloidosis and neuronal degeneration, 61 inhibit neuronal apoptosis by the activation of the PINK1-Parkin-mediated mitophagy signaling pathway, 62 increase the DHA content by up-regulating independent phospholipase A2 (iPLA2) and 15-lipoxygenase (15-LOX) to ameliorate oxidative stress and inflammation, 63 modulate the metabolism of monoamine neurotransmitters and protect the ultrastructure of the cortex changed by aging 64 during in vivo experiments. In conclusion, DSS could ameliorate the deterioration of cognition in SAMP8, especially in female animals.…”