Integrating network pharmacology and experimental validation to investigate the effects and mechanism of Renshen Shouwu decoction for ameliorating Alzheimer's disease – PubMed Black Hawk Supplements

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CONTEXT: The mechanism of Renshen Shouwu Decoction (RSSW) in treating Alzheimer’s disease (AD) remains unknown.
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Integrating network pharmacology and experimental validation to investigate the effects and mechanism of Renshen Shouwu decoction for ameliorating Alzheimer's disease - PubMed

. 2024 Dec;62(1):767-780.

doi: 10.1080/13880209.2024.2415660. Epub 2024 Oct 17.

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Integrating network pharmacology and experimental validation to investigate the effects and mechanism of Renshen Shouwu decoction for ameliorating Alzheimer’s disease

Jing-Jing Liu et al. Pharm Biol. 2024 Dec.

Abstract

Context: The mechanism of Renshen Shouwu Decoction (RSSW) in treating Alzheimer’s disease (AD) remains unknown.

Objective: This study investigates the effects and mechanism of RSSW for ameliorating AD.

Materials and methods: Ten SAMR1 mice and 40 SAMP8 mice were divided into five groups: control (SAMR1), model (SAMP8), positive drug (Donepezil, 1.3 mg/kg/d), and RSSW (Low-dose, 117 mg/kg/d; High-dose, 234 mg/kg/d). Starting from 6 months of age, the medications were administered intragastrically for a total of 60 days. Subsequently, memory improvement in rapidly aging mice was assessed using the novel object recognition test and Morris water maze test. Through the identification of absorbed blood components and analysis of network pharmacology, active ingredients and potential targets involved in the treatment of AD were identified. Finally, AD-related biological indicators were detected using western blotting and ELISA.

Result: Our results demonstrated that RSSW effectively ameliorated memory impairments, inhibited tau hyperphosphorylation, and reduced β-amyloid plaque deposition in SAMP8 mice. Thirty absorbed blood components in RSSW were identified, revealing identified 96 major targets that play a key role in alleviating AD. Notably, the obtained main targets were highly enriched in SIRT1-mediated signaling pathways. Subsequent experimental validation confirmed that RSSW activated the SIRT1/NF-κB, SIRT1/AMPK, and SIRT1/p53 signaling cascades. Nine potential active ingredients were predicted through molecular docking.

Discussion and conclusions: Our research findings suggest the mechanism of RSSW treatment for AD, which ameliorates memory impairments by reducing cortical tissue inflammation and apoptosis.

Keywords: Polygoni multiflori; Radix Praeparata; Red ginseng; SIRT1; aging; apoptosis; inflammation.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.

RSSW ameliorates cognitive dysfunction in SAMP8. (A) Discrimination index in novel object recognition, n = 6. (B) Movement trajectory in the water maze, n = 6. (C) Escape latency in the water maze, n = 6. (D) Target crossings in the water maze, n = 6. (E) The levels of Aβ1-42 in brain cortex tissues quantified by ELISA, n = 6. (F) The protein expressions of tau and p-tau in brain cortex tissues determined by Western blot, n = 3. (G) and (H) The histogram shows the protein expression levels of tau and p-tau normalized with β-actin in all groups, n = 3. The results were presented as mean ± SD, #p < 0.05, ##p < 0.01, ###p < 0.005, ####p < 0.001 vs. SAMR1 group. *p < 0.05, **p < 0.01, ***p < 0.005, ****p < 0.001 vs. SAMP8 group.

Figure 2.
Figure 2.

GO term performance and pathway enrichment analysis of the major hubs. (A) GO term performance by biological process (BP); (B) GO term performance by cellular component (CC); (C) GO term performance by molecular function (MF); and (D) pathway enrichment analysis by KEGG. The ordinate stands for GO terms or the main pathways, the primary abscissa stands for minus log10(P), and the secondary abscissa stands for the percentage of major hubs involved in the corresponding GO terms or the main pathways out of total major hubs.

Figure 3.
Figure 3.

Major hubs-major pathways PPI network. Round green nodes represent putative targets of RSSW; round red nodes represent AD associated targets; round yellow nodes represent both RSSW targets and AD associated targets; blue rectangles represent top 12 pathways from enrichment analysis of major hubs; edges represent interactions among RSSW putative targets, AD associated targets, and main pathways.

Figure 4.
Figure 4.

RSSW ameliorates AD via activating SIRT1-mediated signaling pathways. (A–I) The histogram shows the protein expression levels of SIRT1, p53, Ace-p53, Bax, Bcl-2, Bcl-2/Bax, p65, Ace-p65, p-AMPK/AMPK (normalized with β-actin), n = 3. (J,K) The protein expression of SIRT1, p53, Ace-p53, Bax, Bcl-2, p65, Ace-p65, AMPK, and p-AMPK were determined by western blots.

Figure 5.
Figure 5.

The levels of TNF-α (a), IL-1β (B), and IL-6 (C) in mouse brain tissues quantified by ELISA.

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Grants and funding

Shuang-cheng Ma received the support of National Natural Science Foundation of China (Grant number 81973476) and Ying Wang received the support of the Training Fund for Academic Leaders of NIFDC (Grant number 2023 × 8).

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Integrating network pharmacology and experimental validation to investigate the effects and mechanism of Renshen Shouwu decoction for ameliorating Alzheimer's disease – PubMed