Shenqi formula delayed Alzheimer's disease-like symptoms by skn-1 pathway in Caernorhabditis elegans.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenqi formula is composed of Codonopsis pilosula (Cp) and Lycium barbarum (Lb), and it is traditionally used for promoting qi and nourishing the spleen, liver and kidney. Cp and Lb have been reported to improve cognitive performance in APP/PS1 mice, prevent the accumulation of Aß, and reduce the neurotoxicity of Aß to achieve the anti-Alzheimer's disease (AD) effect. AIM OF THE STUDY: Shenqi formula was explored the therapeutic effect on Caenorhabditis elegans AD pathological model and the underlying mechanism of action. MATERIALS AND METHODS: Paralysis assay and serotonin sensitivity assay was used to detect whether Shenqi formula can alleviate AD paralysis phenotype, and then DPPH, ABTS, NBT and Fenton methods were applied to investigate the scavenging capacity to free radical, ROS, ·O2- and ·OH of Shenqi formula in vitro. H2DCF-DA and MitoSOX™ Red were employed to measure ROS and .O2- accumulation, respectively. RNAi was used to knock down the expression of skn-1 and daf-16 related to oxidative stress resistance signalling pathway. Fluorescence microscopy was used to record the expression of SOD-3::GFP, GST-4::GFP, SOD-1::YFP, and the nuclear translocation of SKN-1 and DAF-16. Western blot assay was carried out to test Aß monomers and oligomers. RESULTS: Shenqi formula delayed the AD-like pathological characteristics in C. elegans, and the complete Shenqi formula was more effective than Cp or Lb alone. The effect of Shenqi formula on delaying worm paralysis was partially eliminated by skn-1 RNAi, but not daf-16 RNAi. Shenqi formula significantly inhibited the abnormal deposition of Aß protein, decreased Aß protein monomers and oligomers. It increased the expressions of gst-4, sod-1, and sod-3 similar to paraquat, companied by rise then fall of ROS and .O2- in AD worms. CONCLUSIONS: Shenqi formula at least partially depended on SKN-1 signalling pathway to exert its anti-AD effect, and it is potential to be used as a kind of health food to prevent the progress of AD.

cep-1 mediated the mitohormesis effect of Shengmai formula in regulating Caenorhabditis elegans lifespan.

Ageing is one of the major causes of many diseases such as cardiovascular diseases, diabetes, neurodegenerative disorders, and cancer. It has been found that mitochondrion acts as a crucial regulator of healthy lifespan. In this work, traditional Chinese medicine Shengmai formula (SMH) was used to treat mitochondrial mutants of Caenorhabditis elegans. The results showed that SMH shortened the lifespan of short-lived mev-1 mutant, but lengthened the lifespan of long-lived isp-1 mutant. Acute SMH treatment has benefit effect by increasing resistance capacity and motion activity in both ETC mutants and wild type N2. Compared with N2, the genome-wide transcriptome profile of ETC mutants showed on a similar pattern after SMH treatment. GO and KEGG enrichment analysis addressed that SMH-induced genes mainly enriched in metabolic process and oxidation-reduction process. The ROS levels in ETC mutants and N2 firstly rose then fell after SMH treatment, in company with the elevation of SOD-1, SOD-3 and GST-4, the increment of HSP-16.2 combined with heat shock. SMH increased oxygen consumption and ATP content, improved the restoration of mitochondrial homeostasis. SMH-induced opposed lifespan outcomes were markedly counteracted by cep-1 RNAi, together with the mitochondrial dynamics. Western blot assay also demonstrated a SMH-induced CEP-1 expression. Collectively, SMH acts as a prooxidant to regulate mitochondrial homeostasis and causes mitohormesis to exert therapeutic effect based on the redox background of the recipients, and cep-1 was required for the mitochondrial hormetic responses. The results shed a light on the rational clinical anti-ageing applications of SMH in the future.

A new highly oxygenated germacranolide from Carpesium nepalense var. lanatum (C.B.Clarke) Kitam.

A new highly oxygenated germacranolide, carcerlane A (1), together with four known highly oxygenated germacranolides (2-5), was isolated from an ethanol extract of the whole plant of Carpesium nepalense var. lanatum (C.B.Clarke) Kitam. The structures were determined by HRESIMS and extensive analysis of their spectroscopic data including IR, 1 D and 2 D NMR spectra. To our best knowledge, it was the first time to report the phytochemical investigation on this plant. The anti-Alzheimer's disease (AD) activities of 1-5 were evaluated using Caenorhabditis elegans AD pathological model. All the tested compounds showed that they have the anti-AD bioactivities of delaying worms paralysis.

HSF-1 mediated combined ginsenosides ameliorating Alzheimer's disease like symptoms in Caernorhabditis elegans.

There are few effective medications to treat Alzheimer's disease (AD). It has been suggested that several ginsenosides possess mild or moderate anti-AD activity. In our present work, a preferred combined ginsenosides was shown to have a more significant benefit effect on AD-like symptoms of worm paralysis and hypersensitivity to exogenous 5-HT in C. elegans. The combined ginsenosides can suppress Aß deposits and Aß oligomers, alleviating the toxicity induced by Aß overexpression more effectively than used alone. Its anti-AD effect was partially abolished by hsf-1 RNAi knocked down or hsf-1 inactivation by point mutation, but not by daf-16 or skn-1 RNAi knocked down. Furthermore, it markedly activated hsp-16.2 gene expression downstream of HSF-1. Our results demonstrated that HSF-1 signaling pathway exerts an important role in mediating the therapeutic effect of combined ginsenosides on AD worms. These results provided powerful evidences and theoretical foundation for reshaping medicinal products of ginsenosides and ginseng on prevention of neurodegenerative diseases.