This study was designed to evaluate the ameliorating effects of curculigoside fromCurculigo orchioidesGaertn on learning and memory in aged rats. In the present study, the ameliorating effects of curculigoside were determined through animal behaviour studies (including step-down test and Y-maze test), and the possible mechanisms were explored by evaluation of the activity of acetylcholinesterase (AchE) and determination of the expression of BACE1. Oral adminstration of the curculigoside (20, 40 mg/kg/day) for 14 days can significantly improve the latency and number of errors in aged rats based on the behaviour study results. In addition, the activity of AchE can be decreased by treatment of the curculigoside (10, 20, 40 mg/kg/day). Moreover, the expression of BACE1 can be down-regulated in the hippocampus of aged rats treated with curculigoside. The results of our present work have indicated that curculigoside can improve cognitive function in aged animals, possibly by decreasing the activity of AchE in the cerebra and inhibiting the expression of BACE1 in the hippocampus. In conclusion, our results suggested that curculigoside can be possible developed as a new drug for the treatment of Alzheimer’s disease in the future.Keywords:curculigoside;Curculigo orchioides;Alzheimer’s disease;behaviour study;ameliorative effects on learning and memory
Wei Li,Chong Qiao,Jing Pang,Guolin Zhang,Yinggang Luo
Amaryllidaceae alkaloids are unique benzylphenethylamine derivatives that comprise of more than 600 members with a huge chemical diversity. Most of them showed interesting bioactivities, for instance, galanthamine (GAL) is clinically used for Alzheimer's disease treatment. All Amaryllidaceae alkaloids had been thought to be derived from 4′- O -methylnorbelladine originated from norbelladine catalyzed by norbelladine 4′- O -methyltransferase (N4OMT). Herein we mined the transcriptome datasets of Lycoris radiata , a GAL-producing plant. LrOMT was cloned, overexpressed in Escherichia coli , and purified to homogeneity. Bioinformatics analysis and enzymatic activity assays revealed that LrOMT is an S-adenosylmethionine-dependent Class I OMT. LrOMT exhibited both para - and meta - O -methylation activities toward norbelladine to give 4′- and 3′- O -methylnorbelladine. Twenty-four analogues, including the proposed biosynthetic intermediates, were introduced to investigate the substrate scope of LrOMT and it showed that the aromatic substrates should have two vicinal hydroxyl groups. The LrOMT-catalyzed O -methylation preference is dependent on the properties of the binding group of the substrates. The transcription levels of LrOMT were positively associated with the accumulation of the Amaryllidaceae alkaloids and the biosynthetic intermediates in L. radiata . The present work revealed that LrOMT catalyzes multiple O -methylation reactions and its characterization will be helpful to uncover novel biosynthetic genes for Amaryllidaceae alkaloids biosynthesis.
There is considerable interest in the utilisation of plants against inflammation. Over 50 species of the plant family Amaryllidaceae are known for such usage in traditional medicine. This review was undertaken to identify the chemical principles responsible for these anti-inflammatory effects. It describes the findings from in vitro, in vivo and in silico studies, as well as the probes made on the mechanisms of action. The literature search returned over 600 hits, of which around 130 were chosen for their relevance to the text. Over 140 compounds have thus far been screened for anti-inflammatory effects. These were mostly isoquinoline alkaloids but also included other classes of secondary metabolites such as chromones, flavonoids and triterpenoids. In vitro studies were carried out in mononuclear cells such as lymphocytes, monocytes, neutrophils and macrophages, against which no serious side effects were observed. The constituents were also effective against inflammation induced by physical and chemical stimuli in a variety of murine test subjects. Chief among the compounds were the isoquinoline alkaloids lycorine and narciclasine, which displayed potent effects against pain, swelling, asthma and arthritis, amongst others. From a mechanistic perspective, several of the compounds were shown to mediate in inflammatory pathways, notably via the modulation of both pro-inflammatory (such as NF-κB, TNF-α and IL-1) and anti-inflammatory (such as IL-10 and TGF-β) factors. Useful insights also emerged from active-site docking studies of some of the compounds. The Amaryllidaceae affords a rich and diverse platform for the discovery of potential anti-inflammatory drugs.
Hu Jiawei,Li Wei,Liu Zhan,Zhang Guolin,Luo Yinggang
Tyrosine decarboxylase (TyDC), a pyridoxal-5′-phosphate (PLP)-dependent aromatic amino acid decarboxylase, catalyzes the decarboxylation of l -tyrosine (Tyr) to generate the important biogenic tyramine. This amine was reported to be a biosynthetic precursor of the Amaryllidaceae alkaloids, a group of pharmaceutically important natural products. Herein, we cloned two TyDC-encoding genes from Lycoris radiata , a galanthamine (GAL, a characteristic Amaryllidaceae alkaloid)-producing and medicinally and ornamentally important perennial herbaceous plant. Heterologous expression of LrTyDC s in Escherichia coli and the following purification gave recombinant LrTyDCs to homogeneity for enzymatic reactions. Tyramine was detected and validated by HPLC–DAD and HRESIMS analyses of the LrTyDC-catalyzed reaction mixture, which revealed the catalytic decarboxylation activity of LrTyDCs. The transcriptional LrTyDC s were detected in all tissues of L. radiata by quantitative real-time PCR analyses. The present works demonstrated that TyDC-catalyzed decarboxylation reaction is a key step to generate the non-catechol biosynthetic precursor of the Amaryllidaceae alkaloids.