Neuroprotective Effects of Oligosaccharides in Rehmanniae Radix on Transgenic Caenorhabditis elegans Models for Alzheimer’s Disease

Abstract

Rehmanniae Radix (RR, the dried tuberous roots of Rehmannia glutinosa (Gaertn.) DC.) is an important traditional Chinese medicine distributed in Henan, Hebei, Inner Mongolia, and Northeast in China. RR is frequently used to treat diabetes mellitus, cardiovascular disease, osteoporosis and aging-related diseases in a class of prescriptions. The oligosaccharides and catalpol in RR have been confirmed to have neuroprotective effects. However, there are few studies on the anti-Alzheimer’s disease (AD) effect of oligosaccharides in Rehmanniae Radix (ORR). The chemical components and pharmacological effects of dried Rehmannia Radix (DRR) and prepared Rehmannia Radix (PRR) are different because of the different processing methods. ORR has neuroprotective potential, such as improving learning and memory in rats. Therefore, this study aimed to prove the importance of oligosaccharides in DRR (ODRR) and PRR (OPRR) for AD based on the Caenorhabditis elegans (C. elegans) model and the different roles of ODRR and OPRR in the treatment of AD. In this study, we used paralysis assays, lifespan and stress resistance assays, bacterial growth curve, developmental and behavioral parameters, and ability of learning and memory to explore the effects of ODRR and OPRR on anti-AD and anti-aging. Furthermore, the accumulation of reactive oxygen species (ROS); deposition of Aβ; and expression of amy-1, sir-2.1, daf-16, sod-3, skn-1, and hsp-16.2 were analyzed to confirm the efficacy of ODRR and OPRR. OPRR was more effective than ODRR in delaying the paralysis, improving learning ability, and prolonging the lifespan of C. elegans. Further mechanism studies showed that the accumulation of ROS, aggregation, and toxicity of Aβ were reduced, suggesting that ORR alleviated Aβ-induced toxicity, in part, through antioxidant activity and Aβ aggregation inhibiting. The expression of amy-1 was downregulated, and sir-2.1, daf-16, sod-3, and hsp-16.2 were upregulated. Thus, ORR could have a possible therapeutic effect on AD by modulating the expression of amy-1, sir-2.1, daf-16, sod-3, and hsp-16.2. Furthermore, ORR promoted the nuclear localization of daf-16 and further increased the expression of sod-3 and hsp-16.2, which significantly contributed to inhibiting the Aβ toxicity and enhancing oxidative stress resistance. In summary, the study provided a new idea for the development of ORR.

Radix Rehmanniae Praeparata (Shu Dihuang) exerts neuroprotective effects on ICV-STZ-induced Alzheimer’s disease mice through modulation of INSR/IRS-1/AKT/GSK-3β signaling pathway and intestinal microbiota

“…RRP is widely used as primal medicine in Chinese herbal formula for the treatment of AD or diabetes, for example, Qi Fu Yin, Qidan Dihuang decoction, Zhibai Dihuang Wan, Dihuang Yinzi, and Liuwei Dihuang ( Chen et al, 2018 ; Ong et al, 2018 ; Lu et al, 2020 ; Lee et al, 2021 ; Song et al, 2022 ). Several studies have reported that the components in RRP are effective against AD ( Huang et al, 2016 ; Kang et al, 2022 ). In this study, we investigated the protective effects and potential mechanisms of RRP in ICV-STZ-induced AD mice to provide a basis for further clinical application of RRP.…”

Novel Flavonol Alkaloids in Green Tea: Synthesis, Detection, and Anti-Alzheimer’s Disease Effect in a Transgenic Caenorhabditis elegans CL4176 Model

“…The initial number of nematodes in each plate was 30, each with three repeats. The nematodes were transferred to new plates every other day and the number of deaths was counted daily until all died …”

“…The nematodes were transferred to new plates every other day and the number of deaths was counted daily until all died. 35 CL4176 Strain Reproduction Assay. The synchronized CL4176 nematodes at the breeding stage were transferred to the NGM with inactivated OP50 and corresponding compounds (myricetin, quercetin, 1, 2, 3, and 4 at 100 μM, with 0.1% DMSO as the control group).…”

P-hydroxybenzaldehyde protects Caenorhabditis elegans from oxidative stress and β-amyloid toxicity

“…Image J software was used to analyze the images and subtract the background signal from all readings. For the TJ356 strain, worm plates that were cultured in blank medium for 72 h and then warmed to 37°C for 30 min of induction were used as positive controls.SKN-1::GFP fluorescence intensities were measured in the intestinal region of LD1 worms under the pharynx, and the nucleus localization of DAF-16 was expressed as the number of fluorescence points per worm ( Kang et al, 2022 ). Furthermore, whole-body worms were measured using Image J software to analyze the fluorescence intensity associated with the expression of SOD-3::GFP and GST-4::GFP in CF1553 and CL2166 worms, and the experiments were independently replicated three times, with a minimum of 10 worms in each group for each experiment.…”