ABSTRACT
Physalin B (PB), one of the major active steroidal constituents of Solanaceae Physalis plants, has a wide variety of biological activities. We found that PB significantly down-regulated β-amyloid (Aβ) secretion in N2a/APPsw cells. However, the underlying mechanisms are not well understood. In the current study, we investigated the changes in key enzymes involved in β-amyloid precursor protein (APP) metabolism and other APP metabolites by treating N2a/APPsw cells with PB at different concentrations. The results indicated that PB reduced Aβ secretion, which was caused by down-regulation of β-secretase (BACE1) expression, as indicated at both the protein and mRNA levels. Further research revealed that PB regulated BACE1 expression by inducing the activation of forkhead box O1 (FoxO1) and inhibiting the phosphorylation of signal transducer and activator of transcription 3 (STAT3). In addition, the effect of PB on BACE1 expression and Aβ secretion was reversed by treatment with FoxO1 siRNA and STAT3 antagonist S3I-201. In conclusion, these data demonstrated that PB can effectively down-regulate the expression of BACE1 to reduce Aβsecretion by activating the expression of FoxO1 and inhibiting the phosphorylation of STAT3.
Subject(s)
Humans , Alzheimer Disease , Amyloid Precursor Protein Secretases/metabolism , Amyloid beta-Peptides/metabolism , Aspartic Acid Endopeptidases/metabolism , Down-Regulation , Forkhead Box Protein O1/genetics , Phosphorylation , STAT3 Transcription Factor/metabolism , SecosteroidsABSTRACT
Objective: To investigate the chemical constituents from whole herb of Physalis angulata and test their cytotoxic activity. Methods: Compounds were isolated by chromatography methods and LC-MS guided analysis, structures were determined by spectroscopic techniques of 1D- and 2D-NMR (HSQC, HMBC, 1H-1H COSY, and NOESY), cytotoxic activity experiments were conducted by MTT method. Results: Twelve compounds were identified as physalins A (1), B (2), C (3), D (4), F (5), H (6), I (7), O (9), 5α-ethoxy-6β-hydroxy-5,6-dihydrophysalin B (8), β-sitosterol (10), 2-carboxyoxanilic acid methyl ester (11), and acetaminobenzoic acid (12). Conclusion: Among these compounds, compound 11 is a new natural product. Compounds 1-3 and 9 are firstly obtained from P. angulata. All compounds are tested for their inhibitory activities against human lung adenocarcinoma strain A-549, with IC50 values of 1.9-20.2 μmol/L, which indicates good cytotoxic activity of these physalins.
ABSTRACT
Objective To study the in-vitro anti-tumor activities of physalin B (PhB) extracted from Physalis angulata L.. Methods Th e effect of PhB on the cell proliferation and the morphology changes of tumor cell strains HepG2 and SGC7901 was observed by methyl thiazolyl tetrazolium (MTT) assay and by phase contrast microscopy respectively, and the results were compared to positive control anti-cancer drug hydroxycamptothecine (HCTP) . Apoptosis of HepG2 and SGC7901 cells induced by PhB was determined by 4’ , 6-diamidino-2-phenylindole ( DAPI) staining method. Results MTT results showed that the growth of HepG2 and SGC7901 was significantly inhibited by PhB in dose-and time-dependent manner, and the inhibitory effect of high concentration of PhB was better than the positive control medicine HCTP. Phase contrast microscopy results showed that the cellular morphology was improved by PhB, which was accorded with the results showed by MTT assay. DAPI staining results showed that the apoptosis of HepG2 and SGC7901 was enhanced by PhB. Conclusion PhB extracted from Physalis pubescens L. exerts certain inhibitory effect on the proliferation of HepG2 and SGC7901 cells.