• Nutrition Research and Practice
• /
• v.14 no.5
• /
• pp.478-489
• /
• 2020

BACKGROUND/OBJECTIVES: Morusin, a marker component of Morus alba L., possesses anti-cancer activity. The objective of this study was to determine autophagy-inducing effect of morusin in non-small cell lung cancer (NSCLC) cells and investigate the underlying mechanism. SUBJECTS/METHODS: Autophagy induction and the expression of autophagy-related proteins were analyzed by LC3 immunofluorescence and western blot, respectively. The role of autophagy and AMP-activated protein kinase (AMPK) was determined by treating NSCLC cells with bafilomycin A1, an autophagy inhibitor, and compound C, an AMPK inhibitor. Cytotoxicity and apoptosis induction were determined by MTT assay, trypan blue exclusion assay, annexin V-propidium iodide (PI) double staining assay, and cell cycle analysis. RESULTS: Morusin increased the formation of LC3 puncta in the cytoplasm and upregulated the expression of autophagy-related 5 (Atg5), Atg12, beclin-1, and LC3II in NSCLC cells, demonstrating that morusin could induce autophagy. Treatment with bafilomycin A1 markedly reduced cell viability but increased proportions of sub-G1 phase cells and annexin V-positive cells in H460 cells. These results indicate that morusin can trigger autophagy in NSCLC cells as a defense mechanism against morusin-induced apoptosis. Furthermore, we found that AMPK and its downstream acetyl-CoA carboxylase (ACC) were phosphorylated, while mammalian target of rapamycin (mTOR) and its downstream p70S6 kinase (p70S6K) were dephosphorylated by morusin. Morusin-induced apoptosis was significantly increased by treatment with compound C in H460 cells. These results suggest that morusin-induced AMPK activation could protect NSCLC cells from apoptosis probably by inducing autophagy. CONCLUSIONS: Our findings suggest that combination treatment with morusin and autophagy inhibitor or AMPK inhibitor might enhance the clinical efficacy of morusin for NSCLC.

• Tuberculosis and Respiratory Diseases
• /
• v.77 no.2
• /
• pp.65-72
• /
• 2014

Background: It is valuable to find the potential activity of regulating the excessive mucin secretion by the compounds derived from various medicinal plants. We investigated whether aqueous extract of the root bark of Morus alba L. (AMA), kuwanon E, kuwanon G, mulberrofuran G, and morusin significantly affect the secretion and production of airway mucin using in vivo and in vitro experimental models. Methods: Effect of AMA was examined on hypersecretion of airway mucin in sulfur dioxide-induced acute bronchitis in rats. Confluent NCI-H292 cells were pretreated with ethanolic extract, kuwanon E, kuwanon G, mulberrofuran G, or morusin for 30 minutes and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 hours. The MUC5AC mucin secretion and production were measured by enzyme-linked immunosorbent assay. Results: AMA stimulated the secretion of airway mucin in sulfur dioxide-induced bronchitis rat model; aqueous extract, ethanolic extract, kuwanon E, kuwanon G, mulberrofuran G and morusin inhibited the production of MUC5AC mucin induced by PMA from NCI-H292 cells, respectively. Conclusion: These results suggest that extract of the root bark and the natural products derived from Morus alba L. can regulate the secretion and production of airway mucin and, at least in part, explains the folk use of extract of Morus alba L. as mucoregulators in diverse inflammatory pulmonary diseases.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.44 no.7
• /
• pp.1090-1099
• /
• 2015

Among the four different parts of mulberry (Morus alba L.) tree, ethanol extract of Morus root bark showed the highest ${\alpha}$-glucosidase inhibitory activity ($IC_{50}=12.01{\mu}g/mL$). Bioassay-guided fractionation of the ethanolic extract of root bark by Diaion HP-20, silica gel, ODS-A, and Sephadex LH-20 column chromatographies led to the isolation of four compounds, including Compound (Comp.) 1 ($IC_{50}=5.22{\mu}g/mL$), Comp. 2 ($IC_{50}=1.78{\mu}g/mL$), Comp. 3 ($IC_{50}=2.94{\mu}g/mL$), and Comp. 4 ($IC_{50}=1.54{\mu}g/mL$) with strong ${\alpha}$-glucosidase inhibitory activities. Their chemical structures were elucidated as morusin (Comp. 1), kuwanon H (Comp. 2), chalcomoracin A (Comp. 3), and chalcomoracin B (Comp. 4) by UV and NMR spectral analyses. These results suggest that prenylflavonoid and mulberrofuran of Morus root bark may be useful as potential therapeutic agents for diabetes.

• Analytical Science and Technology
• /
• v.30 no.3
• /
• pp.130-137
• /
• 2017

The leaves (Mori Folium; MF), branches (Mori Ramulus; MR), and root bark (Mori Cortex Radicis; MCR) of the mulberry tree have been used as therapeutic herbs for centuries. Existing analytical methods were developed specifically for different parts of the tree and cannot be applied to samples containing a mixture of tree parts. Such method specialization is time-consuming and requires separate identification and quality control of each tree part. This report describes an HPLC method for the simultaneous quality control and discrimination of MF, MR, and MCR using four marker compounds: rutin, kuwanon G, oxyresveratrol, and morusin. An Optimapak $C_{18}$ column ($4.6{\times}250mm$, $5{\mu}m$) was used with a gradient elution of 0.1 % formic acid in water and acetonitrile. The flow rate was 1.0 mL/min and the detection wavelength was 270 nm. In quantitative analyses of the three parts, rutin (0.11 % w/w) was detected only in MF. The oxyresveratrol content (0.12 % w/w) was highest in MR. Kuwanon G (0.33 % w/w) and morusin (0.18 % w/w) were higher in MCR than in other parts. The HPLC method given herein can be used to simultaneously classify and quantify three herbal medicines from the mulberry tree.

• Natural Product Sciences
• /
• v.24 no.4
• /
• pp.266-271
• /
• 2018

Five new prenylated stilbenes (1 - 5), along with the known compounds cudraflavone C, trans-4-isopentenyl-3,5,2',4'-terahydroxystilbene, trans-4-(3-methyl-E-but-1-enyl)-3,5,2',4'-tetrahydroxystilbene, pannokin G, cycloartobiloxanthone, artonin P, morusin, artocarpin, artonin E, kuwanon C, artobiloxanthone, and artoindonesianin C (6 - 17) were isolated from the stem bark of the tropical tree Artocarpus communis. The structures were established by NMR spectroscopic analysis, MS studies, and comparison with spectral data reported in the literature.

• Natural Product Sciences
• /
• v.25 no.3
• /
• pp.268-274
• /
• 2019

Morus alba L., known as white mulberry, is a medicinal plant belongs to family Moraceae. It has long been used commonly in Ayurvedic for the treatment of lung-heat, cough, asthma, hematemesis, dropsy and hypertension. In the present study, seven prenylated flavonoids, along with four benzofuran compounds were isolated by means of repeated column chromatography. The structures of the known compounds were identified as kuwanon G (1), kuwanon E (2), kuwanon T (3), morusin (4), sanggenon A (5), sanggenon M (6), sanggenol A (7), moracin R (8), mulberofuran G (9), mulberofuran A (10) and mulberofuran B (11), by comparing their spectroscopic data with those reported in the literature. For these isolates, containing trace compounds, the inhibitory activity against IL-6 production in $TNF-{\alpha}$ stimulated MG-63 cells was examined. All isolated compounds (1 - 11) showed excellent inhibitory activity against IL-6 production in $TNF-{\alpha}$ stimulated MG-63 cells. Especially this study is first time to report that sanggenon A (5), sanggenon M (6), sanggenol A (7), mulberofuran G (9), mulberofuran A (10) and mulberofuran B (11) showed the inhibitory activity of IL-6 production. Our study suggested the possibility of anti-inflammatory regulation by compounds (1 - 11) isolated from M. alba.