Questin

Inhibitory activities of major anthraquinones and other constituents from Cassia obtusifolia against beta-secretase and cholinesterases.[Pubmed:27321278]

J Ethnopharmacol. 2016 Sep 15;191:152-160.

ETHNOPHARMACOLOGICAL RELEVANCE: Semen Cassiae has been traditionally used as an herbal remedy for liver, eye, and acute inflammatory diseases. Recent pharmacological reports have indicated that Cassiae semen has neuroprotective effects, attributable to its anti-inflammatory actions, in ischemic stroke and Alzheimer's disease (AD) models. AIM OF THE STUDY: The basic goal of this study was to evaluate the anti-AD activities of C. obtusifolia and its major constituents. Previously, the extract of C. obtusifolia seeds, was reported to have memory enhancing properties and anti-AD activity to ameliorate amyloid beta-induced synaptic dysfunction. However, the responsible components of C. obtusifolia seeds in an AD are currently still unknown. In this study, we investigated the inhibitory effects of C. obtusifolia and its constituents against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) enzyme activity. MATERIALS AND METHODS: In vitro cholinesterase enzyme assays by using AChE, BChE, and BACE1 were performed. We also scrutinized the potentials of Cassiae semen active component as BACE1 inhibitors via enzyme kinetics and molecular docking simulation. RESULTS: In vitro enzyme assays demonstrated that C. obtusifolia and its major constituents have promising inhibitory potential against AChE, BChE, and BACE1. All Cassiae semen constituents exhibited potent inhibitory activities against AChE and BACE1 with IC50 values of 6.29-109microg/mL and 0.94-190microg/mL, whereas alaternin, Questin, and toralactone gentiobioside exhibited significant inhibitory activities against BChE with IC50 values of 113.10-137.74microg/mL. Kinetic study revealed that alaternin noncompetitively inhibited, whereas cassiaside and emodin showed mixed-type inhibition against BACE1. Furthermore, molecular docking simulation results demonstrated that hydroxyl group of alaternin and emodin tightly interacted with the active site residues of BACE1 and their relevant binding energies (-6.62 and -6.89kcal/mol), indicating a higher affinity and tighter binding capacity of these compounds for the active site of BACE1. CONCLUSION: The findings of the present study suggest the potential of C. obtusifolia and its major constituents for use in the development of therapeutic or preventive agents for AD, especially through inhibition of AChE, BChE and BACE1 activities.

Immunomodulatory constituents from an ascomycete, Microascus tardifaciens.[Pubmed:10553639]

Chem Pharm Bull (Tokyo). 1999 Oct;47(10):1426-32.

Fractionation guided by the immunosuppressive activity of the defatted AcOEt extract of an Ascomycete, Microascus tardifaciens, afforded eight constituents, Questin (emodin 8-O-methylether) (1), rubrocristin (2), 5,7-dihydroxy-4-methylphthalide (3), cladosporin (asperentin) (4), cladosporin 8-O-methylether (5), tradioxopiperazine A [cyclo-L-alanyl-5-isopentenyl-2-(1',1'-dimethylallyl)-L-tryptophan] (6), tradioxopiperazine B [cyclo-L-alanyl-7-isopentenyl-2-(1',1'-dimethylallyl)-L-tryptophan] (7), and asperflavin (8), among which 6 and 7 were new compounds. Compounds 1 and 2 showed considerably high immunosuppressive activity, 6 was moderate and, 3, 4, 5, 7 and 8 showed low activity.

Anthraquinones, Cdc25B phosphatase inhibitors, isolated from the roots of Polygonum multiflorum Thunb.[Pubmed:17497420]

Nat Prod Res. 2007 May 20;21(6):487-93.

Three anthraquinones, Cdc25B phosphatase inhibitors, were isolated from the methanolic extract of the roots of Polygonum multiflorum Thunb. (Polygonaceae). Anthraquinones, physcion (1), emodin (2), and Questin (3), inhibited the enzymatic activity of Cdc25B phosphatase with IC(50) values of 62.5, 30, and 34 microg mL(-1), respectively. Emodin (2) and Questin (3) strongly inhibited the growth of human colon cancer cells, SW620 with GI(50) values of 6.1 and 0.9 microg mL(-1), respectively. Commercially available anthraquinones, chrysophanol (4), and rhein (5) also inhibited Cdc25B phosphatase with IC(50) values of 10.7 and 22.1 microg mL(-1), respectively.

Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic to lung cells.[Pubmed:22319557]

PLoS One. 2012;7(2):e29906.

Inhalation of Aspergillus fumigatus conidia can cause severe aspergillosis in immunosuppressed people. A. fumigatus produces a large number of secondary metabolites, some of which are airborne by conidia and whose toxicity to the respiratory tract has not been investigated. We found that spores of A. fumigatus contain five main compounds, tryptoquivaline F, fumiquinazoline C, Questin, monomethylsulochrin and trypacidin. Fractionation of culture extracts using RP-HPLC and LC-MS showed that samples containing Questin, monomethylsulochrin and trypacidin were toxic to the human A549 lung cell line. These compounds were purified and their structure verified using NMR in order to compare their toxicity against A549 cells. Trypacidin was the most toxic, decreasing cell viability and triggering cell lysis, both effects occurring at an IC(5)(0) close to 7 microM. Trypacidin toxicity was also observed in the same concentration range on human bronchial epithelial cells. In the first hour of exposure, trypacidin initiates the intracellular formation of nitric oxide (NO) and hydrogen peroxide (H(2)O(2)). This oxidative stress triggers necrotic cell death in the following 24 h. The apoptosis pathway, moreover, was not involved in the cell death process as trypacidin did not induce apoptotic bodies or a decrease in mitochondrial membrane potential. This is the first time that the toxicity of trypacidin to lung cells has been reported.