Dendrobium officinale phenolic extract maintains proteostasis by regulating autophagy in a Caenorhabditis elegans model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and accumulating evidence suggested that proteostatic imbalance is a key feature of the disease. Traditional Chinese medicine exhibits a multi-target therapeutic effect, making it highly suitable for addressing protein homeostasis imbalance in AD. Dendrobium officinale is a traditional Chinese herbs commonly used as tonic agent in China. In this study, we investigated protection effects of D. officinale phenolic extract (SH-F) and examined its underlying mechanisms by using transgenic Caenorhabditis elegans models. We found that treatment with SH-F (50 µg/mL) alleviated Aß and tau protein toxicity in worms, and also reduced aggregation of polyglutamine proteins to help maintain proteostasis. RNA sequencing results showed that SH-F treatment significantly affected the proteolytic process and autophagy-lysosomal pathway. Furthermore, we confirmed that SH-F showing maintainance of proteostasis was dependent on bec-1 by qRT-PCR analysis and RNAi methods. Finally, we identified active components of SH-F by LC-MS method, and found the five major compounds including koaburaside, tyramine dihydroferulate, N-p-trans-coumaroyltyramine, naringenin and isolariciresinol are the main bioactive components responsible for the anti-AD activity of SH-F. Our findings provide new insights to develop a treatment strategy for AD by targeting proteostasis, and SH-F could be an alternative drug for the treatment of AD.

Arecoline excites the contraction of distal colonic smooth muscle strips in rats via the M3 receptor-extracellular Ca2+ influx - Ca2+ store release pathway.

Areca is a Chinese herbal medicine that is widely used for constipation. However the mechanisms of its action are not clear. We investigated the effects of arecoline, the most active component of areca, on the motility of rat distal colonic smooth muscle strips. In longitudinal muscle of distal colon (LMDC) and circular muscle of distal colon (CMDC), arecoline increased the contraction in a dose-dependent manner. Tetrodotoxin (TTX) did not inhibit the effects of arecoline. The contractile response to arecoline was completely antagonized by atropine. 4-Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) strongly depressed the response to arecoline, but gallamine and methoctramine did not. Nifedipine, 2-aminoethoxydiphenyl borate (2-APB), and Ca2+-free Krebs solution with EGTA partly inhibited the effects of arecoline. The sum of Ca2+-free Krebs solution, EGTA, and 2-APB completely inhibited the effects of arecoline. The results show that arecoline stimulates distal colonic contraction in rats via the muscarinic (M3) receptor - extracellular Ca2+ influx - Ca2+ store release pathway. It is likely that the action of areca in relieving constipation is due to its stimulation of muscle contraction.