Effect of Lycoris chejuensis and Its Active Components on Experimental Models of Alzheimer’s Disease

Abstract

We found that an extract of Lycoris chejuensis and its three isolated active components, narciclasine, 7-deoxynarciclasine, and 7-deoxy-trans-dihydronarciclasine, each significantly reduced the formation of amyloid-β peptides in HeLa cells transfected with an amyloid precursor protein carrying the Swedish mutation up to 45 ± 3.6%. The extract down-regulated amyloid precursor protein, especially the mature form by up to 88%, and reduced the ability of secretases to generate toxic amyloid-β. Double-transgenic mice treated with the extract for 4 months also showed significantly reduced levels of amyloid-β and plaques while exhibiting improved memory functions in the Morris water maze and novel object recognition tests. In conclusion, the extract and isolated active components of L. chejuensis decreased the production of amyloid-β by attenuating amyloid precursor protein levels. Furthermore, the extract improved the disrupted memory functions in animals while inhibiting amyloid plaque formation. Thus, this extract, as well as its active components, could prove beneficial in the treatment of Alzheimer's disease.

7‐Deoxynarciclasine shows promising antitumor efficacy by targeting Akt against hepatocellular carcinoma

“…7‐deoxynarciclasine (7‐DONCS), an active narciclasine alkaloid from Lycoris radiata (Amaryllidaceae), exhibits various biological effects, including anticancer, plant growth‐inhibitory, anti‐Alzheimer's disease and antiparasitic activities. The various biological activities and low toxicity of 7‐DONCS make it a promising candidate for clinical development . Previous studies have reported that 7‐DONCS potentially suppresses the proliferation of various cancer cells, such as ascites cancer, breast cancer, colon cancer, leukemia, lung cancer, pancreas cancer and prostate cancer .…”

“…The various biological activities and low toxicity of 7-DONCS make it a promising candidate for clinical development. [10][11][12][13][14] Previous studies have reported that 7-DONCS potentially suppresses the proliferation of various cancer cells, such as ascites cancer, breast cancer, colon cancer, leukemia, lung cancer, pancreas cancer and prostate cancer. 11,[14][15][16] However, the defined targets or molecular mechanisms underlying 7-DONCSregulated tumorigenesis inhibition still remain unveiled.…”

Substrate-Specific Activation of α-Secretase by 7-Deoxy-Trans-Dihydronarciclasine Increases Non-Amyloidogenic Processing of β-Amyloid Protein Precursor

“…Previously, we have confirmed that three active components of CJ, E144, Narciclasine (E2), and 7-Deoxynarciclasine (E3), can decrease the production of Aβ by attenuating APP levels [32]. Since E2 and E3 were structural analogs of E144, we tested whether E2 and E3 could affect the activities of ADAM10 and ADAM17.…”

“…Especially, ADAM17 participates in the shedding of diverse inflammatory factors [31]. For these reasons, a small molecule ADAM activator for AD treatment should be specific for APP sparing other substrates to avoid many deleterious consequences.We have shown the effect of Lycoris chejuensis K. Tae et S. Ko (CJ) originated from Jeju Island in Korea on Aβ generation and spatial memory ability both in vivo and in vitro [32]. Recently, we have identified 7-Deoxy-trans-dihydronarciclasine (Figure 1; coded as E144) as the active component of CJ [33].…”

“…We have shown the effect of Lycoris chejuensis K. Tae et S. Ko (CJ) originated from Jeju Island in Korea on Aβ generation and spatial memory ability both in vivo and in vitro [32]. Recently, we have identified 7-Deoxy-trans-dihydronarciclasine (Figure 1; coded as E144) as the active component of CJ [33].…”