Protective effect of Terminalia chebula Retz. extract against Aβ aggregation and Aβ-induced toxicity in Caenorhabditis elegans

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 A beta, to detect the effect of TWE on improving A beta-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 A beta 1-42 induced toxicity and A beta 1-42 aggregation. Materials and methods: Using transgenic C.elegans strain CL2006 and CL4176 as models respond to paralytic induced by A beta 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 A beta in the transgenic C.elegans, Thioflavin S (ThS) staining and WB visualized the levels of A beta monomers and oligomers. Results: TWE treatment can significantly improve the paralysis of transgenic C.elegans caused by A beta aggregation (up to 14%). The A beta 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 A beta 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 A beta 1-42-induced toxicity, inhibition A beta 142 aggregation and delaying A beta-induced paralysis. The neuroprotective effect of TWE involves the activation of DAF-16/HSF-1/Hsp-16.2 pathway.

Automated summary

The study demonstrates that Terminalia chebula extract can protect C.elegans against A beta 1-42-induced toxicity, inhibit A beta 142 aggregation, and delay A beta-induced paralysis through the activation of the DAF-16/HSF-1/Hsp-16.2 pathway.