Protective effect of Terminalia chebula Retz. extract against Aβ aggregation and Aβ-induced toxicity in Caenorhabditis elegans. (25th March 2021) - Zhao, Longhe
Abstract: Ethnopharmacological relevance: Terminalia chebula Retz. ( T.chebula ) is an important medicinal plant in Tibetan medicine and Ayurveda. T.chebula is known as the "King of Tibetan Medicine", due to its widespread clinical pharmacological activity such as anti-inflammatory, antioxidative, antidiabetic as well as anticancer in lots of in vivo and in vitro models. In this study, we use transgenic and/or RNAi Caenorhabditis elegans ( C.elegans ) model to simulation the AD pathological features induced by Aβ, to detect the effect of TWE on improving Aβ-induced toxicity and the corresponding molecular mechanism. Aim of study: The study aimed to tested the activities and its possible mechanism of T.chebula to against Aβ1-42 induced toxicity and Aβ1-42 aggregation. Materials and methods: Using transgenic C.elegans strain CL2006 and CL4176 as models respond to paralytic induced by Aβ toxicity. The transcription factors DAF-16 and SKN-1 were analyzed used a fluorescence microscope in transgenic strains (DAF-16:GFP, SKN-1:GFP). The function of DAF-16 and SKN-1 was further investigated using loss-of-function strains by feeding RNA interference (RNAi) bacteria. To evaluate the aggregation level of Aβ in the transgenic C.elegans, Thioflavin S (ThS) staining and WB visualized the levels of Aβ monomers and oligomers. Results: TWE treatment can significantly improve the paralysis of transgenic C.elegans caused by Aβ aggregation (up to 14%). The Aβ aggregates in transgenic C.elegans are significantly inhibited under TWE exposure (up to 70%). TWE increases the nuclear localization of the key transcription factor DAF-16 and HSF-1, which in turn leads to the expression of downstream Hsp-16.2 protein and exerts its inhibitory effect on Aβ aggregation. Meanwhile, paralysis improved has not observed in SKN-1 mutation and/or RNAi C.elegans . Conclusion: Our results indicate that TWE can protect C.elegans against the Aβ1-42 -induced toxicity, inhibition Aβ1-42 aggregation and delaying Aβ-induced paralysis. The neuroprotective effect of TWE involves the activation of DAF-16/HSF-1/Hsp-16.2 pathway. Graphical abstract: Image 1 Highlights: The T.chebula water extract (TWE) can delay the paralysis induced by Aβ in transgenic and/or RNA interference C.elegans. TWE shares protective function via reducing the production of Aβ oligomers. TWE plays better effect of delaying Aβ-induced paralysis than the ethanol extract. TWE has the physiological function of cognitive improvement.