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Purpose: To investigate the anticancer effects of the extract mixture of Mori radicis cortex, Mori ramulus, Angelica tenuissima, and Inonotus obliquus extract (MRME), a new herbal preparation from Korea, on B16F10 cells. Methods: The MRME was extracted with water. Cell Counting Kit-8 (CCK-8) assays and 4',6-diamidino-2-phenylindole (DAPI) staining were used to investigate the effect of MRME on cell proliferation and apoptosis in vitro. The expression of p53, p-p53, and phosphorylated Akt (p-Akt) were analyzed by western blotting. Wound-healing assay was used to analyze cell migration. Results: Based on CCK-8 and DAPI staining results, MRME inhibited the growth of B16F10 cells and induced apoptosis in B16F10 cells in a time- and dose-dependent manner (p < 0.05). MRME increased the expression of p53 and p-p53 and decreased the expression of p-Akt in a dose-dependent manner. MRME treatment inhibited cell migration and invasion (p < 0.05). Conclusion: Mori Radicis Cortex Mixture Extract exerts anticancer effect by inducing the expression of p53 and p-p53 and decreasing the expression of p-Akt, which may benefit patients with malignant melanoma when used in combination with v-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitors. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is an inflammation-associated common cancer worldwide. Paejang-san and Mori Cortex Radicis have been traditionally used for treating intestinal inflammatory diseases in Korea and China. In the present study, we developed a new herbal formula as an alternative to CRC treatments, which is composed of two main components of Paejangsan (Patriniae Radix (Paejang in Korean) and Coix Seed (Yiyiin in Korean)), and Mori Cortex Radicis (Sangbekpi in Korean) based on the addition and subtraction theory in traditional medicine, hence the name PSY, and explored the potential therapeutic effects of the new formula PSY in human CRC cells by analyzing viability, cell cycle and apoptosis. We found that PSY ethanol extract (EtOH-Ex), but not water extract, significantly suppressed the viability of human CRC cells, and synergistically decreased the cell proliferation compared to each treatment of Patriniae Radix and Coix Seed extract (PY) or Mori Cortex Radicis extract (S), suggesting the combination of PY and S in a 10-to-3 ratio for the formula PSY. PSY EtOH-Ex in the combination ratio reduced cell viability but induced cell cycle arrest at the G2/M and sub-G1 phases as well as apoptosis in CRC cells. In addition, the experimental results of Western blotting, immunofluorescence staining and reporter assays showed that PSY also inhibited STAT3 by reducing its phosphorylation and nuclear localization, which resulted in lowering STAT3-mediated transcriptional activation. In addition, PSY regulated upstream signaling molecules of STAT3 by inactivating JAK2 and Src and increasing SHP1. Moreover, the chemical profiles of PSY from UPLC-ESI-QTOF MS/MS analysis revealed 38 phytochemicals, including seven organic acids, eight iridoids, two lignans, twelve prenylflavonoids, eight fatty acids, and one carbohydrate. Furthermore, 21 potentially bioactive compounds were highly enriched in the PSY EtOH-Ex compared to the water extract. Together, these results indicate that PSY suppresses the proliferation of CRC cells by inhibiting the STAT3 signaling pathway, suggesting PSY as a potential therapeutic agent for treating CRC and 21 EtOH-Ex-enriched phytochemicals as anti-cancer drug candidates which may act by inhibiting STAT3. [ABSTRACT FROM AUTHOR]

In this study, the underlying mechanisms of metabolic syndrome (MetS) and the risk of AD factors, and the effect of dietary Mori cortex radicis (MCR) were investigated in two in vivo models. In glucose-induced C. elegans, MCR attenuated metabolic disorder by inhibiting lipid and advanced glycation end products (AGEs) production, reducing oxidative stress, and preventing cognition and behavioral deficits. In high fat/liquid sugar-induced MetS mice, MCR intervention improved metabolic alterations and spatial memory. Furthermore, MCR in diet suppressed AGEs deposit and RAGE expression, improved the antioxidant system, and decreased pro-inflammatory cytokine levels in mouse hippocampus. This was accompanied by downregulation of the MAPK (p38, ERK, and JNK) pathway, which consequently protected against brain damage by suppressing BACE-1, APP, Tau, and Aβ. These findings may be valuable for those investigating crosstalk between MetS and neurodegenerative disease progression or the effect of MCR on the AGE-RAGE/MAPK pathway.

Colorectal cancer (CRC) is an inflammation-associated common cancer worldwide. Paejang-san and Mori Cortex Radicis have been traditionally used for treating intestinal inflammatory diseases in Korea and China. In the present study, we developed a new herbal formula as an alternative to CRC treatments, which is composed of two main components of Paejangsan (Patriniae Radix (Paejang in Korean) and Coix Seed (Yiyiin in Korean)), and Mori Cortex Radicis (Sangbekpi in Korean) based on the addition and subtraction theory in traditional medicine, hence the name PSY, and explored the potential therapeutic effects of the new formula PSY in human CRC cells by analyzing viability, cell cycle and apoptosis. We found that PSY ethanol extract (EtOH-Ex), but not water extract, significantly suppressed the viability of human CRC cells, and synergistically decreased the cell proliferation compared to each treatment of Patriniae Radix and Coix Seed extract (PY) or Mori Cortex Radicis extract (S), suggesting the combination of PY and S in a 10-to-3 ratio for the formula PSY. PSY EtOH-Ex in the combination ratio reduced cell viability but induced cell cycle arrest at the G2/M and sub-G1 phases as well as apoptosis in CRC cells. In addition, the experimental results of Western blotting, immunofluorescence staining and reporter assays showed that PSY also inhibited STAT3 by reducing its phosphorylation and nuclear localization, which resulted in lowering STAT3-mediated transcriptional activation. In addition, PSY regulated upstream signaling molecules of STAT3 by inactivating JAK2 and Src and increasing SHP1. Moreover, the chemical profiles of PSY from UPLC-ESI-QTOF MS/MS analysis revealed 38 phytochemicals, including seven organic acids, eight iridoids, two lignans, twelve prenylflavonoids, eight fatty acids, and one carbohydrate. Furthermore, 21 potentially bioactive compounds were highly enriched in the PSY EtOH-Ex compared to the water extract. Together, these results indicate that PSY suppresses the proliferation of CRC cells by inhibiting the STAT3 signaling pathway, suggesting PSY as a potential therapeutic agent for treating CRC and 21 EtOH-Ex-enriched phytochemicals as anti-cancer drug candidates which may act by inhibiting STAT3.

Norovirus is a major cause of acute gastroenteritis globally, resulting in enormous health and societal costs. In this study, the antiviral activities of Mori Cortex Radicis (MCR) extract and its bioactive flavonoids, morusin and kuwanon G, were tested against murine norovirus (MNV), a human norovirus surrogate, using plaque assay. The antiviral activity was confirmed in simulated digestive conditions, including simulated saliva fluid (SSF), simulated gastric fluid (SGF), and simulated intestinal fluid (SIF). Pre-treatment of MNV with MCR extract at 1000 µg/mL showed antiviral activity with a 1.1-log reduction. Morusin and kuwanon G also demonstrated a 1.0-log and 0.6-log reductions of MNV titers, respectively, at 100 µM. MCR extract at a concentration of 2 mg/mL in SSF, SGF, and SIF markedly reduced MNV titers by 1.8, 1.9, and 1.5 logs, respectively. Therefore, these data suggest that MCR extract can be used to control norovirus infectivity. [ABSTRACT FROM AUTHOR]

This study was undertaken to investigate the neuroprotective effect of an ethanolic extract of Mori Cortex radicis (MCR) against high glucose (HG)-induced oxidative damage in PC12 cells. Cell cytotoxicity was examined using MTT and lactate dehydrogenase assays. To examine the antioxidative effects, intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels and the activities of antioxidant enzymes were measured. The expressions of apoptosis-associated proteins were assessed. MCR was found to increase the viabilities of HG-induced PC12 cells and to inhibit ROS and MDA production and to promote antioxidative enzyme activities. Furthermore, MCR reduced apoptosis by upregulating p-Akt and Bcl-2/Bax ratio and reducing cytochrome c level. The main flavonoids in MCR were identified by HPLC to be kuwanon G and morusin. These results suggest the antioxidative effects of MCR protect against HG-induced oxidative stress and that MCR has potential therapeutic use for the prevention and treatment of diabetic neuro-degeneration. Protective effect of MCR against HG-induced oxidative stress and its major compounds kuwanon G and morusin [ABSTRACT FROM AUTHOR]

Present study was conducted to investigate ameliorating effects of Mori Cortex radicis on cognitive impair and neuronal defects in HFD-induced (High Fat Diet-Induced) obese mice. To induce obesity, C57BL/6 mice were fed an HFD for 8 weeks, and then mice were fed the HFD plus Mori Cortex radicis extract (MCR) (100 or 200 mg/kg/day) for 6 weeks. Prior to sacrifice, body weights were measured, and Y-maze test and oral glucose tolerance test were performed. Serum lipid metabolic biomarkers (TG, LDL, and HDL/total cholesterol ratio) and antioxidant enzymes (glutathione, superoxide dismutase, and catalase), malondialdehyde (MDA), and acetylcholinesterase (AChE) levels were measured in brain tissues. The expressions of proteins related to insulin signaling (p-IRS, PI3K, p-Akt, and GLUT4) and neuronal protection (p-Tau, Bcl-2, and Bax) were examined. MCR suppressed weight gain, improved serum lipid metabolic biomarker and glucose tolerance, inhibited AChE levels and MDA production, and restored antioxidant enzyme levels in brain tissue. In addition, MCR induced neuronal protective effects by inhibiting p-Tau expression and increasing Bcl-2/Bax ratio, which was attributed to insulin-induced increases in the expressions p-IRS, PI3K, p-Akt, and GLUT4. These indicate MCR may reduce HFD-induced insulin dysfunction and neuronal damage and suggest MCR be considered a functional material for the prevention of T2DM-associated neuronal disease.

Objective Chinese crude drug Mori Cortex Radicis (the root cortex of Morus species) has been used as a folk medicine to treat hypertension, diabetes, as well as in expectorant, diuretic agents. This investigation aims to study the anti-hyperlipidemia effects of Mori Cortex Radicis (MCR) extracts in hyperlipidemic rat models and the potential therapeutic activities of compounds isolated from the extracts. Materials and methods The effects of MCR on hypolipidemic parameters were investigated using Wistar rats induced by high-lipid emulsion. Sixty healthy Wistar rats were randomly divided into 6 groups: normal group, hyperlipidaemia model group, simvastatin, and high-, medium- and low-dose MCR extracts. After four weeks, body weight, total cholesterol (TC), triglycerides (TG), high and low-density lipoproteins (HDL, LDL), as well as aspartate aminotransferase (AST), alanine aminotransferase (ALT) were measured. To further investigation, four major active compounds were isolated from extracts through high performance liquid chromatography (HPLC) and their diacylglycerol acyltransferase 1 (DGAT1) inhibitory activity was evaluated. Results MCR dose-dependently reduced serum TC, TG, LDL-C, inhibited the activity of ALT, AST, and increased HDL-C. Furthermore, in vitro biochemistry tests revealed that four active isolates showed moderate inhibitory activity against DGAT1 with IC 50 values ranging from 62.1±1.2 to 99.3±2.3 µM. Conclusions The results demonstrated that MCR could effectively ameliorate hyperlipidaemia and inhibit DGAT1 that a key enzyme closely related to hyperlipidaemia and type 2 diabetes. It may provide a new pharmacological basis for treating hyperlipidaemia and related diseases using MCR. [ABSTRACT FROM AUTHOR]

Mori Cortex Radicis ( MCR), the dried root bark of Morus alba L., is a well-known traditional herbal medicine. While several studies have examined the components and bioactivities of MCR, this study describes the development of a method for the simultaneous quantitative evaluation of two marker compounds for quality control and classification of MCR samples. Two marker compounds of MCR, kuwanon G and morusin, were separated and quantified using high-performance liquid chromatography ( HPLC) on an Optimapak C18 column (4.6 × 250 mm, 5 µm). The compounds were eluted with a mobile phase of water and methanol under gradient conditions (0 min at 15% B, 5 min at 70% B, 30 min at 100% B) at a flow rate of 1.0 mL/min and a detection wavelength of 270 nm. The method was validated with respect to linearity, accuracy, precision, and recovery. The results satisfied the guidelines set by the Ministry of Food and Drug Safety ( MFDS), Korea. The validated method was applied to the quantification of the two marker compounds in 81 samples (65 MCRs, 16 similar crude drugs) collected from various regions of Korea and China. Using a linear regression method, content criteria were established in accordance with the quantitative results obtained with the two marker compounds of MCR. Therefore, the developed HPLC method is suitable for quality control and classification of MCR samples according to harvesting country. [ABSTRACT FROM AUTHOR]

The root bark of Morus alba L. (Mori Cortex Radicis; MCR) is traditionally used in Korean medicine for upper respiratory diseases. In this study, we investigated the antiasthmatic effect of kuwanon G isolated from MCR on ovalbumin (OVA)-induced allergic asthma in mice. Kuwanon G (1 and 10 mg/kg) was administered orally in mice once a day for 7 days during OVA airway challenge. We measured the levels of OVA-specific IgE and Th2 cytokines (IL-4, IL-5, and IL-13) in the sera or bronchoalveolar lavage (BAL) fluids and also counted the immune cells in BAL fluids. Histopathological changes in the lung tissues were analyzed. Kuwanon G significantly decreased the levels of OVA-specific IgE and IL-4, IL-5, and IL-13 in the sera and BAL fluids of asthma mice. Kuwanon G reduced the numbers of inflammatory cells in the BAL fluids of asthma mice. Furthermore, the pathological feature of lungs including infiltration of inflammatory cells, thickened epithelium of bronchioles, mucus, and collagen accumulation was inhibited by kuwanon G. These results indicate that kuwanon G prevents the pathological progression of allergic asthma through the inhibition of lung destruction by inflammation and immune stimulation. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

[Display omitted] • MCR suppressed lipid and AGEs accumulation and ROS, and improved cognitive functions in glucose-fed C. elegans. • MCR attenuated metabolic disorder and spatial memory in high fat/liquid sugar diet-fed mouse. • Diet-induced MetS mouse model increased AGEs deposit, pro-inflammatory cytokines and AD-related factors. • These MetS derived neuronal damages was inhibited by MCR intake via AGE-RAGE/MAPK pathway. In this study, the underlying mechanisms of metabolic syndrome (MetS) and the risk of AD factors, and the effect of dietary Mori cortex radicis (MCR) were investigated in two in vivo models. In glucose-induced C. elegans , MCR attenuated metabolic disorder by inhibiting lipid and advanced glycation end products (AGEs) production, reducing oxidative stress, and preventing cognition and behavioral deficits. In high fat/liquid sugar-induced MetS mice, MCR intervention improved metabolic alterations and spatial memory. Furthermore, MCR in diet suppressed AGEs deposit and RAGE expression, improved the antioxidant system, and decreased pro-inflammatory cytokine levels in mouse hippocampus. This was accompanied by downregulation of the MAPK (p38, ERK, and JNK) pathway, which consequently protected against brain damage by suppressing BACE-1, APP, Tau, and Aβ. These findings may be valuable for those investigating crosstalk between MetS and neurodegenerative disease progression or the effect of MCR on the AGE-RAGE/MAPK pathway. [ABSTRACT FROM AUTHOR]

In our efforts to find neuroprotective materials of plant origin, several compounds were isolated from Mori Cortex Radicis. The protective effect against dopamine-induced cell death was examined, and the subsequent effects on the levels of expression of Parkinson's disease-associated nurr1 and α-synuclein were evaluated in a dopamine-induced system. Five compounds were isolated and moracenin D protected cell death against dopamine-induction in human neuroblastoma SH-SY5Y cells. The effects of moracenin D on the levels of mRNA and protein expression of nurr1 and α-synuclein were subsequently examined using reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. Treatment with moracenin D resulted in an up-regulation of nurr1 mRNA levels and a down-regulation of α-synuclein mRNA levels. Additionally, the α-synuclein protein expression was decreased in accordance with an increase in nurr1 protein expression. These results demonstrate that the protective effects of moracenin D were presumably due to the correlative effects on the up-regulation of nurr1 and down-regulation of α-synuclein expressions against dopamine induction. Therefore, moracenin D can be considered as a candidate for therapy for Parkinson's disease. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Seven prenylated flavanoids, licoflavone C ( 1), cyclomulberrin ( 2), neocyclomorusin ( 3), sanggenon I ( 4), morusin ( 5), kuwanon U ( 6) and kuwanon E ( 7), and three 2-arylbenzofurans, moracin P ( 8), moracin O ( 9), and mulberrofuran Q ( 10) were isolated from the MeOH extract of Mori Cortex Radicis. Among these, compounds 2- 7 enhanced cell viability in a dose-dependent manner against sodium nitroprusside-induced cell death in neuroblastoma SH-SY5Y cells, which was measured by MTT reduction assay (EC values of 4.4, 5.6, 8.0, 6.4, 8.7, and 11.9 μg/mL, respectively). Among 10 compounds, C-3 prenylated flavones ( 2, 3, and 5) and prenylated flavanones ( 4, 6, and 7) showed cell protection. However, compound 1 which lacks the prenyl group at C-3 and three 2-arylbenzofurans ( 8- 10) did not show protective effect. The order of cell protection was as follow: C-3 prenylated flavones ( 2, 3, and 5) > prenylated flavanones ( 4, 6, and 7) > 2-arylbenzofurans ( 8- 10) and flavone ( 1). From this result, we show that some prenylated flavones and flavanones might protect neuronal cells against nitrosative stress-mediated cell death. Even though further evaluations are necessary in vitro and in vivo study, we carefully suggest that some prenylated flavonoids from Mori Cortex Radicis might protect neuronal cells from neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Three known 2-arylbenzofurans, moracin P ( 1), moracin O ( 2) and mulberrofuran Q ( 3) were isolated from the MeOH extract of the Mori Cortex Radicis. These compounds 1- 3 enhanced cell viability in dose-dependent manner against oxygen-glucose deprivation (OGD)-induced cell death in neuroblastoma SH-SY5Y cells, which was measured by MTT reduction assay. (EC values of 10.4, 12.6, and 15.9 μM, respectively). In addition, the compounds 1-3 were examined for their inhibitory effect on OGD-induced ROS production by FACS analysis. We observed these compounds reduced ROS production in OGD-induced cell death (IC values of 1.9, 0.3 and 12.1 μM, respectively). Consequently, reactive oxygen species (ROS) were overexpressed in OGD-induced cells and all three compounds reduced ROS induced by OGD in dosedependent manner. Taken together, compounds 1-3 might protect neuronal cell death against the oxidative stress induced by OGD, though further studies in vitro and in vivo models are necessary. [ABSTRACT FROM AUTHOR]

Present study was conducted to investigate ameliorating effects of Mori Cortex radicis on cognitive impair and neuronal defects in HFD-induced (High Fat Diet-Induced) obese mice. To induce obesity, C57BL/6 mice were fed an HFD for 8 weeks, and then mice were fed the HFD plus Mori Cortex radicis extract (MCR) (100 or 200 mg/kg/day) for 6 weeks. Prior to sacrifice, body weights were measured, and Y-maze test and oral glucose tolerance test were performed. Serum lipid metabolic biomarkers (TG, LDL, and HDL/total cholesterol ratio) and antioxidant enzymes (glutathione, superoxide dismutase, and catalase), malondialdehyde (MDA), and acetylcholinesterase (AChE) levels were measured in brain tissues. The expressions of proteins related to insulin signaling (p-IRS, PI3K, p-Akt, and GLUT4) and neuronal protection (p-Tau, Bcl-2, and Bax) were examined. MCR suppressed weight gain, improved serum lipid metabolic biomarker and glucose tolerance, inhibited AChE levels and MDA production, and restored antioxidant enzyme levels in brain tissue. In addition, MCR induced neuronal protective effects by inhibiting p-Tau expression and increasing Bcl-2/Bax ratio, which was attributed to insulin-induced increases in the expressions p-IRS, PI3K, p-Akt, and GLUT4. These indicate MCR may reduce HFD-induced insulin dysfunction and neuronal damage and suggest MCR be considered a functional material for the prevention of T2DM-associated neuronal disease. [ABSTRACT FROM AUTHOR]