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This study investigated the neuroprotective effects of Dendropanax morbifera leaves and stems (DMLS) water extract on scopolamine (SCO)-induced memory impairment in mice. First, we conducted experiments to determine the protective effect of DMLS on neuronal cells. Treatment with DMLS showed a significant protective effect against neurotoxicity induced by Aβ(25–35) or H2O2. After confirming the neuroprotective effects of DMLS, we conducted animal studies. We administered DMLS orally at concentrations of 125, 250, and 375 mg/kg for 3 weeks. In the Y-maze test, SCO decreased spontaneous alternation, but treatment with DMLS or donepezil increased spontaneous alternation. In the Morris water-maze test, the SCO-treated group showed increased platform reach time and decreased swim time on the target platform. The passive avoidance task found that DMLS ingestion increased the recognition index in short-term memory. Furthermore, memory impairment induced by SCO reduced the ability to recognize novel objects. In the Novel Object Recognition test, recognition improved with DMLS or donepezil treatment. In the mouse brain, except for the cerebellum, acetylcholinesterase activity increased in the SCO group and decreased in the DMLS and donepezil groups. We measured catalase and malondialdehyde, which are indicators of antioxidant effectiveness, and found that oxidative stress increased with SCO but was mitigated by DMLS or donepezil treatment. Thus, our findings suggest that ingestion of DMLS restored memory impairment by protecting neuronal cells from Aβ(25–35) or H2O2-induced neurotoxicity, and by reducing oxidative stress. [ABSTRACT FROM AUTHOR]

This study investigated the neuroprotective effects of Dendropanax morbifera leaves and stems (DMLS) water extract on scopolamine (SCO)-induced memory impairment in mice. First, we conducted experiments to determine the protective effect of DMLS on neuronal cells. Treatment with DMLS showed a significant protective effect against neurotoxicity induced by Aβ(25–35) or H2O2. After confirming the neuroprotective effects of DMLS, we conducted animal studies. We administered DMLS orally at concentrations of 125, 250, and 375 mg/kg for 3 weeks. In the Y-maze test, SCO decreased spontaneous alternation, but treatment with DMLS or donepezil increased spontaneous alternation. In the Morris water-maze test, the SCO-treated group showed increased platform reach time and decreased swim time on the target platform. The passive avoidance task found that DMLS ingestion increased the recognition index in short-term memory. Furthermore, memory impairment induced by SCO reduced the ability to recognize novel objects. In the Novel Object Recognition test, recognition improved with DMLS or donepezil treatment. In the mouse brain, except for the cerebellum, acetylcholinesterase activity increased in the SCO group and decreased in the DMLS and donepezil groups. We measured catalase and malondialdehyde, which are indicators of antioxidant effectiveness, and found that oxidative stress increased with SCO but was mitigated by DMLS or donepezil treatment. Thus, our findings suggest that ingestion of DMLS restored memory impairment by protecting neuronal cells from Aβ(25–35) or H2O2-induced neurotoxicity, and by reducing oxidative stress.

Glioblastoma (GBM) is one of the most dangerous brain tumors in humans. The median survival of patients with GBM is <18 months. Glioma stem-like cells (GSCs), a small subpopulation of cells with stem cell-like characteristics found within GBM, are regarded as the main cause of GBM malignancy. Therefore, targeting GSCs presents an important therapeutic strategy for reducing the aggressiveness of tumors. In this study, we examined effects of (9Z,16S)-16-O-acetyl-9,17-octadecadiene-12,14-diynoic acid (AODA), a diacetylenic carboxylic acid isolated from leaves of Dendropanax morbiferus, on viability and self-renewal activity of GSCs. AODA substantially decreased GSC growth, causing apoptotic cell death as assessed by Annexin V/PI staining and morphological alterations by optical diffraction tomography. Interestingly, treatment with AODA suppressed "stem-like features" in vitro by limiting dilution assays and real-time polymerase chain reaction analysis. In addition, Western blotting revealed that AODA treatment decreased expression levels of phosphorylated AKT and phosphorylated ERK in GSC11 cells. Taken together, our results indicate that AODA could be considered a new therapeutic candidate to target GSCs. [ABSTRACT FROM AUTHOR]

Recently, utilizing natural bioactive compounds for active ingredients in cosmetics has become a growing worldwide trend. More and more studies aim to identify the sources of herbal ingredients for applications in the pharmaceutical and cosmetic fields. Additionally, in order to optimize the safety of natural ingredients, choosing an environmentally friendly extraction method also plays an important role. In this work, an eco-friendly extraction technique for Dendropanax morbifera using microwave treatment and microwave-assisted Dendropanax morbifera extract (MA-DME) was investigated. The results indicate that higher yields of MA-DME were obtained than with conventional methods and that D. morbifera's antioxidant properties were enhanced. Moreover, we found that MA-DME exhibited extraordinary antioxidant, anti-aging, and skin-whitening activities. We suggest MA-DME as a potential cosmeceutical ingredient than could be utilized for comprehensive protection of human skin. [ABSTRACT FROM AUTHOR]

This study examined the anti-diabetic effects of aqueous extracts of Dendropanax morbifera leaves (DMWEs) in streptozotocin-induced diabetic Sprague-Dawley (SD) rats. Thirty male SD rats (body weight [BW], 250.4 ± 19.7 g) were divided into the following six groups: normal control rats (NC), diabetic control rats (DC), diabetic rats treated with metformin HCl 100 mg/kg BW (DT), diabetic rats treated with DMWEs 50 mg/kg BW (DM-50), diabetic rats treated with DMWEs 100 mg/kg BW (DM-100), and diabetic rats treated with DMWEs 200 mg/kg BW (DM-200). From two weeks of administration of DMWEs, the BW of all groups treated with DMWEs increased significantly compared to DC (p < 0.05). At four weeks after treatment, the blood glucose levels in DT, DM-100, and DM-200 decreased below 200 mg/dL, while the glycated hemoglobin concentrations in all groups administered DMWEs were similar to those of NC and DT. Regarding the blood biochemical parameters, the levels of aspartate transaminase, alanine transaminase, blood urea nitrogen, and creatinine in DM-100 and DM-200 were similar to those in NC and DT. Overall, these results highlight the effectiveness of DM-100 in the treatment of diabetes. [ABSTRACT FROM AUTHOR]

The aim of this study was to optimize the extraction method for caffeic acid from the leaves of Dendropanax morbifera using response surface methodology (RSM), and subsequently determine the polyphenolic content and antioxidant capacity of the D. morbifera leaves extracts. The extraction process considered operating variables such as solvent concentration, extraction temperature, and extraction time, which were optimized via Box–Behnken experimental design. In addition, the antioxidant capacity was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The optimal extraction conditions of 41.23% (v/v) methanol concentration, at 88.61 °C, and 1.86 h produced a maximum caffeic acid (CA) yield of 20.35 mg/g. Additionally, total polyphenols, total tannins, and total flavonoids contents in the leaves extracts of D. morbifera were 32.48 ± 2.05 mg GAE (gallic acid equivalents)/g, 17.61 ± 2.61 mg GAE/g, and 9.14 ± 0.17 mg QE (quercetin equivalents)/g, respectively. The results showed that methanol extracts exhibited an IC50 of approximately 14.3 mg AAE (ascorbic acid equivalent)/g. The results suggested that the extracts of D. morbifera leaves contain potential antioxidant activity, and could be a good source of functional food and used in medicinal applications. [ABSTRACT FROM AUTHOR]

Recently, utilizing natural bioactive compounds for active ingredients in cosmetics has become a growing worldwide trend. More and more studies aim to identify the sources of herbal ingredients for applications in the pharmaceutical and cosmetic fields. Additionally, in order to optimize the safety of natural ingredients, choosing an environmentally friendly extraction method also plays an important role. In this work, an eco-friendly extraction technique for Dendropanax morbifera using microwave treatment and microwave-assisted Dendropanax morbifera extract (MA-DME) was investigated. The results indicate that higher yields of MA-DME were obtained than with conventional methods and that D. morbifera’s antioxidant properties were enhanced. Moreover, we found that MA-DME exhibited extraordinary antioxidant, anti-aging, and skin-whitening activities. We suggest MA-DME as a potential cosmeceutical ingredient than could be utilized for comprehensive protection of human skin.

This study aimed to compare the anti-inflammatory activity of 10-year-old Dendropanax morbifera LEV (DM) leaf extracts. The leaves were collected during different seasons (May, August, and November), and the extracts were prepared using different methods (hot water, 30% ethanol, or 60% ethanol). Lipopolysaccharide-stimulated RAW264.7 cells were treated with these extracts for 12 h. The anti-inflammatory effects were evaluated by measuring the production of nitrite; prostaglandin E2 (PGE2); and inflammatory cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha, in addition to the mRNA expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 and activation of the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathways. The amyrin and polyphenol compositions of the extracts were analyzed using a triple time-of-flight mass spectrometer and high-performance liquid chromatography. The 30% ethanol extract harvested in May and 60% ethanol extracts collected in August and November displayed the highest inhibitions of nitrite, PGE2, and inflammatory cytokines. The 60% ethanol extract harvested in August suppressed activation of the NF-κB and MAPK signaling pathways. The contents of amyrin and polyphenol compounds were highly dependent on the ethanol concentration used during each season. These results suggest that ethanol extracts of DM leaves may have the potential to regulate inflammatory responses. [ABSTRACT FROM AUTHOR]

To appraise the effects and involved mechanism of Dendropanax morbifera leaves extract (DLE) on diabetes and retinal degeneration, in this study, male C57BLKS/J-m+/db and five groups of db/db mice were treated with 0.5% CMC or metformin or three doses of DLE for 6 weeks. Administration of DLE stimulated AMP-activated protein kinase in the liver, skeletal muscle and adipose tissue, leading to the improvement of gene and protein expression related with insulin resistance and glucose homeostasis in db/db mice. Morphological changes and insulin depletion of pancreatic islets were also attenuated by treatment of DLE. Moreover, DLE treatment prevented the deterioration of retina by regulating not only the gene expression related with apoptosis and neovascularization, but also the level of activator protein-1 in retina. Therefore, DLE improves diabetic phenotype and retinal degeneration, suggesting that DLE could be a prospective agent for preventing diabetes and related eye complication.

Polyacetylenes in the bark of Dendropanax morbifera trees have been reported to promote immune cell proliferation and to strengthen the innate immune system. The immunomodulatory potential of D. morbifera branch water extract (DBW) was evaluated by determining its effect on cell viability and the expression of cytokines and immune effector molecules in mouse RAW264.7 macrophages and splenocytes. Production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cytokines (interleukin [IL]-1β, IL-2, and IFN-γ) in RAW264.7 macrophages increased after treatment with DBW. The activation of components of the NF-κB signaling pathway, including the phospho-IκBα and the expression and translocation of p65, a subunit of NF-κB, were also increased in RAW264.7 mouse macrophage cells after treatment with DBW. In addition, when mice were orally administered DBW, splenocyte cytokines and NO production were increased in a dose-dependent manner relative to control-treated mice. Furthermore, natural killer cell activity in DBW-treated mice was determined by lactate dehydrogenase (LDH) release assay. LDH release also increased in response to DBW treatment. Taken together, these results indicate that D. morbifera extract enhances innate immunity by promoting NF-κB signaling, leading to increased expression of proinflammatory cytokines and effector molecules. DBW therefore has potential therapeutic use in the context of immune stimulation. [ABSTRACT FROM AUTHOR]

Dendropanax morbifera (DM) extract was co-fermented by Bacillus subtilis HA and Lactobacillus plantarum EJ2014 for producing poly-γ-glutamic acid (γ-PGA) and γ-aminobutyric acid (GABA). The first fermentation with B. subtilis HA resulted in a viscous broth with pH 7.85, 0.01 % acidity, 0.72 mg/g peptides, 17.39 U/g protease activity, 8.44 log CFU/mL B. subtilis, 4.96 Pa•sn consistency index, and 45.84 mg/mL mucilage. For the second fermentation with L. plantarum, the broth was enriched with skim milk. The cofermented broth indicated 0.5 % acidity and pH 5.1. The viable cell counts of B. subtilis decreased, whereas those of L. plantarum increased, as did the peptide content. The MSG precursor was effectively converted to GABA, which showed a concentration of 12.80 mg/mL. Therefore, the co-fermented DM extract was enriched with γ-PGA, GABA, peptides, and probiotics by the serial co-fermentation, and could be used as a potential ingredient for developing functional foods. [ABSTRACT FROM AUTHOR]

Metabolic syndrome is a worldwide health problem, and obesity is closely related to type 2 diabetes, cardiovascular disease, hypertension, and cancer. According to WHO in 2018, the prevalence of obesity in 2016 tripled compared to 1975. D. morbifera reduces bad cholesterol and triglycerides levels in the blood and provides various antioxidant nutrients and germicidal sub-stances, as well as selenium, which helps to remove active oxygen. Moreover, D. morbifera is useful for treating cardiovascular diseases, hypertension, hyperlipidemia, and diabetes. Therefore, we study in vivo efficacy of D. morbifera to investigate the prevention effect of obesity and cholesterol. The weight and body fat were effectively reduced by D. morbifera water (DLW) extract administration to high-fat diet-fed C57BL/6 mice compared to those of control mice. The group treated with DLW 500 mg∙kg−1∙d−1 had significantly lower body weights compared to the control group. In addition, High-density lipoprotein (HDL) cholesterol increased in the group treated with DLW 500 mg∙kg−1∙d−1. The effect of DLW on the serum lipid profile could be helpful to prevent obesity. DLW suppresses lipid formation in adipocytes and decreases body fat. In conclusion, DLW can be applied to develop anti-obesity functional foods and other products to reduce body fat.

Green synthesis of metal nanoparticles from medicinal plants has provided a broad scope in biomedical research and functional food formulations due to low toxicity. Dendropanax morbifera (DM) is a versatile traditional medicine used for various inflammatory diseases due to its extensive antioxidant activity. We investigated DM as a natural capping agent for Zn2+ ions and coloaded it with tryptophan for its penetration and antiobesity behavior. DM zinc oxide nanoparticles (DM-ZnO NPs) were prepared and then entrapped with tryptophan (DM-ZnO-Try nanoemulsion (NE)) for stable formulation using the O/W nanoemulsion method. The hydrodynamic sizes measured by dynamic light scattering for DM-ZnO NPs and DM-ZnO-Try NE are about 146.26 ± 3.31 and 151.16 ± 3.59 nm, respectively. TEM and SEM reveal its morphology. In vitro analysis on both NPs and NE was non-toxic to RAW 264.7 and 3T3-L1 preadipocyte cell line. It significantly reduced the accumulated lipids through lipolysis performed at 10 ug/mL in 3T3-L1 preadipocyte cells. NE suppresses the differentiation of 3T3-L1 adipocytes and lowers triglycerides. Further, the substantial reduction of lipid content is evident with Oil Red O staining and OD measurement. In this present study, the synergetic effect of DM-ZnO NPs and tryptophan is reported, which provides a way for more detailed research on its efficacy for obesity and obesity-associated disorders.

Alzheimer's disease accounts for the majority of dementia and shows hallmarks such as sequential cognitive dysfunction and abnormal behavior. Dendropanax morbifera (DM) has traditionally been used to treat a variety of diseases in East Asia. The aim of this study was to assess the therapeutic effects of DM on brain neuron damage and on cognitive deficit in neuronal cell induced by Aβ1–42 in mice. Treatment with DM reduced the levels of intracellular reactive oxygen species and protected against the death of neuronal cells induced by Aβ1–42 peptide. In addition, it was also found that pretreatment with DM decreased cognitive damage induced by Aβ peptide via enhancing the cholinergic system and antioxidant defense system in mice. Furthermore, the study verified that the change in the expression of both cyclic-adenosine monophosphate response element binding protein and of brain-derived neurotrophic factor in the hippocampus in Aβ peptide-treated mice was significantly ameliorated after treatment with DM. Accordingly, these results suggest that pretreatment with DM defends against oxidative stress and cognitive impairment caused by Aβ peptide. [ABSTRACT FROM AUTHOR]

Dendropanax morbifera (D. morbifera), known as Dendro, means 'omnipotent drug' (Panax), and has been called the panacea tree. Various studies on D. morbifera are currently ongoing, aiming to determine its medicinal uses. The present study investigated the anti-inflammatory effects and underlying mechanism of a natural extract of D. morbifera leaves (DPL) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. In the present study, the following assays and models were used: MTT assay, nitric oxide (NO) assay, western blotting, ELISA and mouse models of atopic dermatitis. DPL extract markedly reduced the production of NO, inducible NO synthase and interleukin-6, as well as the nuclear translocation of nuclear factor-κB (NF-κB). Additionally, the LPS-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2), P38 and c-Jun N-terminal kinase (JNK) was suppressed by DPL extract. Taken together, these results indicate that NF-κB, ERK1/2, P38 and JNK may be potential molecular targets of DPL extract in the LPS-induced inflammatory response. Subsequently, the present study investigated the effects of DPL extract in a 2,4-dinitrochlorobenzene-induced atopic dermatitis mouse model. Ear thickness, serum immunoglobulin E levels and histological analysis revealed that the DPL extract was effective in attenuating the inflammatory response. These results indicate that DPL extract has anti-inflammatory potential and may be developed as a botanical drug to treat atopic dermatitis. [ABSTRACT FROM AUTHOR]

This study compared the antioxidant activity of extracts from Dendropanax morbifera (D. morbifera) Levillis leaves. The concentrations of flavonoids and polyphenols were measured in extracts of D. morbifera leaves. The antioxidant activities were examined by ABTS and DPPH radical scavenging activity and ferric reducing antioxidant power (FRAP). Total flavonoid and polyphenol contents, and FRAP were highest in the 30% ethanol extract collected in May. The ABTS and DPPH radical scavenging activities were the highest in the 60% ethanol extract harvested in May. For investigating the relationship between antioxidant activity and specific polyphenols, rutin and chlorogenic acid of the polyphenol component were quantified by LC-MS/MS analysis. The concentrations of them were highest in the 60% ethanol extract collected in May, and showed positive correlations with antioxidant activities. The optimal extraction conditions to yield the most effective antioxidant activity were obtained using a 60% ethanol extraction solvent with samples collected in May. [ABSTRACT FROM AUTHOR]

This study aimed to compare the anti-inflammatory activity of 10-year-old Dendropanax morbifera LEV (DM) leaf extracts. The leaves were collected during different seasons (May, August, and November), and the extracts were prepared using different methods (hot water, 30% ethanol, or 60% ethanol). Lipopolysaccharide-stimulated RAW264.7 cells were treated with these extracts for 12 h. The anti-inflammatory effects were evaluated by measuring the production of nitrite; prostaglandin E2 (PGE2); and inflammatory cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha, in addition to the mRNA expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 and activation of the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathways. The amyrin and polyphenol compositions of the extracts were analyzed using a triple time-of-flight mass spectrometer and high-performance liquid chromatography. The 30% ethanol extract harvested in May and 60% ethanol extracts collected in August and November displayed the highest inhibitions of nitrite, PGE2, and inflammatory cytokines. The 60% ethanol extract harvested in August suppressed activation of the NF-κB and MAPK signaling pathways. The contents of amyrin and polyphenol compounds were highly dependent on the ethanol concentration used during each season. These results suggest that ethanol extracts of DM leaves may have the potential to regulate inflammatory responses.

This study evaluated the protective effects of Dendropanax morbifera leaf (DML) extracts in the liver due to excessive ethanol consumption. Our results showed that the ethanol extract had better antioxidant activity than the water extract, likely due to the higher levels of total flavonoid and phenolic compounds in the former. We found that the main phenolic acid was chlorogenic acid and the major flavonoid was rutin. Results from the animal model experiment showed concentration-dependent liver protection with the distilled water extract showing better liver protection than the ethanol extract. Gut microbiota dysbiosis induced by alcohol consumption was significantly shifted by DML extracts through increasing mainly Bacteroides and Allobaculum. Moreover, predicted metabolic activities of biosynthesis of beneficial monounsaturated fatty acids such as oleate and palmitoleate were enhanced. Our results suggest that these hepatoprotective effects are likely due to the increased activities of antioxidant enzymes and partially promoted by intestinal microbiota shifts.

Dendropanax morbifera is a versatile plant that has been used as a herbal medicine due to its various useful medicinal effects. To protect its active component from biological stress and increase its drug efficacy as well as drug bioavailability, nanoemulsion was prepared. Dendropanax morbifera zinc oxide nanoparticles (DM-ZnO NPs) were synthesized using the plant extract via the co-precipitation method and loaded with active indole-3-carbinol for nanoemulsion formulation using the ultrasonication process. Field emission transmission electron microscope revealed the flower shape of the Dendropanax morbifera indole-3-carbinol zinc oxide nanoemulsion (DM-ZnO-I3C-NE). In contrast, DM-ZnO NPs showed a spheroid shape that coincides agreeably with field emission electron scanning microscope. The hydrodynamic sizes by dynamic light scattering are about 65 ± 3 nm and 239.6 ± 6 nm and the crystallite sizes from X-ray diffraction are 11.52 nm and 16.07 nm for DM-ZnO NPs and DM-ZnO-I3C-NE, respectively. In vitro analysis revealed the cytotoxicity of DM-ZnO-I3C-NE against a human lung cancer cell line (A549) at 12.5 µg/mL as well as reactive oxygen species (ROS) production. The DM-ZnO-I3C-NE-induced ROS generation level was higher than that of DM-ZnO NPs and free indole-3-carbinol. The synergistic effect of DM-ZnO and indole-3-carbinol indicates DM-ZnO-I3C-NE as a potential candidate for future lung cancer drug and could be scope for functional food.

The response surface methodology was used to optimally extract the antioxidant substances from Dendropanax morbifera leaves. The central composite design was used to optimally analyze the effects of ethanol concentration, sample to solvent ratio, extraction temperature, and extraction time on the total flavonoids (TF) content, ferric reducing antioxidant power (FRAP), and Trolox equivalent antioxidant capacity (TEAC). All three parameters were largely influenced by the ethanol concentration and extraction temperature, while TEAC was also influenced by the sample to solvent ratio. The maximum values of TF content, FRAP, and TEAC were achieved under the following extraction conditions: 70% ethanol, 1:10 sample to solvent ratio, 80 °C, and 14 h. The D. morbifera leaf extracts (DMLE) produced under these optimum extraction conditions were investigated to determine their preventive effects on alcohol-induced liver injury. The DMLE was shown to prevent liver injury by scavenging the reactive oxygen species generated by alcohol. In addition, composition analysis of DMLE found high contents of chlorogenic acid and rutin that were determined to inhibit alcoholic liver injury. The findings of this study suggest that DMLE could prove useful as a functional food product supplement to prevent liver injury caused by excessive alcohol consumption.

The aquatic extract of Dendropanax morbifera (DP) is typically consumed as a beverage in Korea and China and is also used in various traditional medicines. However, the functional role of DP on diabetes-induced renal fibrosis is unclear. Here, the protective effects of DP extract against diabetes-induced renal fibrosis were evaluated. Streptozotocin (STZ, 60 mg/kg) was injected intraperitoneally in rats to induce diabetes. After 5 days, DP extract (25 mg/kg/day) and metformin (50 mg/kg/day) were administered orally to diabetic rats for 28 days. DP administration protected both body and organ weight loss in STZ-treated diabetic rats. Significant improvements in serum blood urea nitrogen (BUN), creatinine, and oxidative stress parameters were observed in diabetic rats by DP administration. DP extract markedly protected diabetic-induced histopathological damages in the kidney and pancreas. A significant reduction was observed in microalbumin, kidney injury molecule-1 (KIM-1), selenium binding protein-1 (SBP1), and pyruvate kinase muscle isozyme M2 (PKM2) levels in the urinary excretion of diabetic rats after the administration of DP extract. The expression of pro-inflammatory cytokines and fibrosis marker levels were significantly reduced in the kidney of diabetic rats. Our results strongly indicate that DP extract exhibits protective activity against diabetes-induced renal fibrosis through ameliorating oxidative stress and inflammation. Therefore, we suggest that DP extract can be used as a preventive agent on the progression of diabetic nephropathy and renal fibrosis.

The extract tea of Dendropanax morbifera is popular beverages in Korea, and their preventive and therapeutic roles in metabolic disorders have been reported. However, the molecular mechanism has not been studied despite the known efficacy of D. morbifera. Eleven fractions (fr.1–fr.11) were divided by MPLC to find the active compound. Among them, Fr.5 was superior to others in that the inhibitory efficacy of de novo triglyceride (TG) biosynthesis. NMR analysis revealed that Fr.5 is composed 98% or more (9Z,16S)-16-hydroxy-9,17-octadecadiene-12,14-diynoic acid (HOD). Treatment of HOD diminished oleic acid (OA)-induced TG accumulation in HepG2 hepatocytes and differentiation of 3T3-L1 preadipocytes by activating LKB1/AMPK. In addition, we determined the effect of the oral administration of the extract of D. morbifera on obesity and hepatic steatosis in high-fat diet (HFD)-induced obese mice. This study proved that D. morbifera containing HOD, the active substance, can show preventive or therapeutic efficacy on obesity and hepatic steatosis through the targeting LKB1/AMPK axis.

Background/Aims: Drug-induced acute kidney injury (AKI) has been a severe threat to hospitalized patients, raising the urgent needs to develop strategies to reduce AKI. We investigated the protective activity of Dendropanax morbifera (DP), a medicinal plant which has been widely used to treat infectious and pain diseases, on acute kidney injury (AKI) using cisplatin-induced nephropathic models. Methods: Both in vitro renal tubular cells (NRK-52E) and in vivo rat models were used to demonstrate the nephroprotective effect of DP. Results: Methanolic extract from DP significantly reduced cisplatin-induced toxicity in renal tubular cells. Through successive liquid extraction, the extract of DP was separated into n-hexane, CHCl3, EtOAc, n-BuOH, and H2O fractions. Among these, the CHCl3 fraction (DPCF) was found to be most potent. The protective activity of DPCF was found to be mediated through anti-oxidant, mitochondrial protective, and anti-apoptotic activities. In in vivo rat models of AKI, treatment with DPCF significantly reversed the cisplatin-induced increase in blood urea nitrogen and serum creatinine and histopathologic damage, recovered the level of anti-oxidant enzymes, and inhibited renal apoptosis. Conclusion: We demonstrated that DP extracts decreased cisplatin-induced renal toxicity, indicating its potential to ameliorate drug-associated acute kidney damage.

An extract of Dendropanax morbifera branch exerts antioxidant, anti-inflammatory, antithrombotic, and anticancer activities. The purpose of this study was to investigate the effect of the extract in isoproterenol-induced cardiac hypertrophy. Phalloidin staining showed that treatment with the extract dramatically prevents isoproterenol-induced H9c2 cell enlargement and the expression of cardiac hypertrophic marker genes, including atrial natriuretic peptide (ANP) and B-type brain natriuretic peptide (BNP). Further, pretreatment with the extract decreased isoproterenol-induced GATA4 and Sp1 expression in H9c2 cells. Overexpression of Sp1 induced the expression of GATA4. The forced expression of Sp1 or its downstream target GATA4, as well as the co-transfection of Sp1 and GATA4 increased the expression of ANP, which was decreased by treatment with the extract. To further elucidate the regulation of the Sp1/GATA4-mediated expression of ANP, knockdown experiments were performed. Transfection with small interfering RNAs (siRNAs) for Sp1 or GATA4 decreased ANP expression. The extract did not further inhibit the expression of ANP reduced by the transfection of GATA4 siRNA. Sp1 knockdown did not affect the expression of ANP that was induced by the overexpression of GATA4; however, GATA4 knockdown abolished the expression of ANP that had been induced by Sp1 overexpression. The extract treatment also attenuated the isoproterenol-induced activation of p38 MAPK, ERK1/2, and JNK1. Hesperidin, catechin, 2,5-dihydroxybenzoic acid, and salicylic acid are the main phenolic compounds present in the extract as observed by high performance liquid chromatography. Hesperidin and 2,5-dihydroxybenzoic acid attenuated isoproterenol-induced cardiac hypertrophy. These findings suggest that the D. morbifera branch extract prevents cardiac hypertrophy by downregulating the activation of Sp1/GATA4 and MAPK signaling pathways. [ABSTRACT FROM AUTHOR]

To appraise the effects and involved mechanism of Dendropanax morbifera leaves extract (DLE) on diabetes and retinal degeneration, in this study, male C57BLKS/J-m+/db and five groups of db/db mice were treated with 0.5% CMC or metformin or three doses of DLE for 6 weeks. Administration of DLE stimulated AMP-activated protein kinase in the liver, skeletal muscle and adipose tissue, leading to the improvement of gene and protein expression related with insulin resistance and glucose homeostasis in db/db mice. Morphological changes and insulin depletion of pancreatic islets were also attenuated by treatment of DLE. Moreover, DLE treatment prevented the deterioration of retina by regulating not only the gene expression related with apoptosis and neovascularization, but also the level of activator protein-1 in retina. Therefore, DLE improves diabetic phenotype and retinal degeneration, suggesting that DLE could be a prospective agent for preventing diabetes and related eye complication. [ABSTRACT FROM AUTHOR]

Methanol (MeOH) extract of the aerial parts of Dendropanax morbifera (Araliaceae) has demonstrated a significant dose-dependent inhibitory effect on the RANKL-induced differentiation of bone marrow-derived macrophages to osteoclasts. Bioassay-guided fractionation of the extract resulted in the isolation of a novel diacetylene carboxylic acid (1), together with a known diacetylenic compounds (2) as phytochemicals to strongly inhibit the osteoclast differentiation. The chemical structure of 1 was determined by spectroscopic analyses as (9Z,16S)-16-O-acetyl-9,17-octadecadiene-12,14-diynoic acid, that is acetyl derivative of 2. Two diacetylenic components of D. morbifera, 1 and 2 exhibited a dose-dependent inhibitory effect on the RANKL-induced formation of tartrate-resistant acid phosphatase-positive multinucleated cells with IC50 values of 2.4 and 3.1 μM, respectively. Seven other known components (3-9) were also isolated from the extract: dendropanoxide (3), friedelin (4), epifriedelanol (5), α-amyrin (6), β-amyrin (7), β-sitosterol (8), and stigmasterol (9). The significant anti-osteoclastogenic activities of 3, 4, 5, and 7 were first reported in this study. [ABSTRACT FROM AUTHOR]

Dendropanax morbifera Leveille (Araliaceae) is an endemic species that grows in Southwestern Korea and has been used as a folk medicine. Several studies reported that D. morbifera leaves have diverse therapeutic potentials. We found that the water extract of D. morbifera leaves increased the growth of EL-4 T cells. The water extract was divided into five fractions: -hexane, chloroform, ethyl acetate, -butanol, and water layers. The ethyl acetate (W-EA) fraction showed a more significant effect than the other fractions on the growth of EL-4 T cells, splenocytes, and isolated murine CD4 T cells. We evaluated the W-EA fraction for its immunomodulatory effects focusing on T cell functions. First, we tested the effect of the W-EA fraction on the regulation of interleukin-2 (IL-2), a potent T cell growth factor. The W-EA fraction significantly increased IL-2 secretion in EL-4 T cells activated with phorbol 12-myristate 13-acetate (PMA) and ionomycin (Io). In addition, the W-EA fraction increased interferon-gamma (IFN- production in isolated murine splenocytes activated with Concanavalin A (ConA). Next, we examined the effect of the W-EA fraction on the regulation of transcriptional factors related to IL-2 production in T cells. The W-EA fraction significantly increased PMA/Io-induced promoter activity of a nuclear factor of activated T cells (NF-AT) in EL-4 T cells, but did not show any significant effects on the promoters of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B). These results indicate that the W-EA fraction from water extract of D. morbifera leaves enhances IL-2 production at the transcriptional levels via the up-regulation of NF-AT in PMA/Io-activated EL-4 T cells. [ABSTRACT FROM AUTHOR]

Dendropanax morbifera Leveille (Araliaceae) has been used in traditional oriental remedies for cancer, inflammation, diabetes, and thrombosis. However, a validated analytical method, standardization, and optimization of extraction conditions with respect to biological activity have not been reported. In this study, a simple and validated HPLC method for identifying and quantifying active substances in D. morbifera was developed. Hot water and ethanolic D. morbifera leaf extracts from different production regions were prepared and evaluated with regard to their chemical compositions and biological activities. The contents of active compounds such as rutin and chlorogenic acid were determined in four samples collected from different regions. The 80% ethanolic extract showed the best antioxidant activity, phenolic content, reducing power, and xanthine oxidase (XO) inhibitory activity. The validated HPLC method confirmed the presence of chlorogenic acid and rutin in D. morbifera leaf extracts. The antioxidant and XO inhibitory activity of D. morbifera extract could be attributed to the marker compounds. Collectively, these results suggest that D. morbifera leaves could be beneficial for the treatment or prevention of hyperuricemia-related disease, and the validated HPLC method could be a useful tool for the quality control of food or drug formulations containing D. morbifera. [ABSTRACT FROM AUTHOR]

Postmenopausal women aged 50s generally experience gradual changes in body such as decline in antioxidant and estrogen levels as the body ages. To overcome these aging-associated changes, the needs for health functional foods are increasing. Dendropanax morbifera (DM) have antioxidant effects, anti-inflammatory against cancer cells, antidiabetic, and antiatherogenic effect which are associated with postmenopausal symptoms. We analyzed clinical effects of DM on aging-related symptoms by reporting their antioxidant, anticancer and inflammatory activity, etc. and their bioactivity. Data sources EMBASE, SCOPUS, PubMed, Web of Science, and Google Scholar databases were searched up to August 2016 for studies investigating medicinal plants in prevention and treatment of diabetes. The search terms were “Dendropanax morbifera”. The reference lists of articles were also reviewed for additional relevant studies. Extracts of DM have various efficacy such as antioxidant, anti-cancer, antiinflammatory activity and anti-thrombotic effect. [ABSTRACT FROM AUTHOR]

Use of the chemotherapeutic agent cisplatin (CDDP) in cancer patients is limited by the occurrence of acute kidney injury (AKI); however, no protective therapy is available. We aimed to investigate the renoprotective effects of Dendropanax morbifera water extract (DM) on CDDP-induced AKI. Male Sprague-Dawley rats (six animals/group) received: Vehicle (control); CDDP (6 mg/kg, intraperitoneally (i.p.); DM (25 mg/kg, oral); or DM + CDDP injection. CDDP treatment significantly increased blood urea nitrogen (BUN), serum creatinine (sCr), and pro-inflammatory cytokines (IL-6 and TNF-α), and severely damaged the kidney architecture. Urinary excretion of protein-based AKI biomarkers also increased in the CDDP-treated group. In contrast, DM ameliorated CDDP-induced AKI biomarkers. It markedly protected against CDDP-induced oxidative stress by increasing the activity of endogenous antioxidants and reducing the levels of pro-inflammatory cytokines (IL-6 and TNF-α). The protective effect of DM in the proximal tubules was evident upon histopathological examination. In a tumor xenograft model, administration of DM enhanced the chemotherapeutic activity of CDDP and exhibited renoprotective effects against CDDP-induced nephrotoxicity without altering chemotherapeutic efficacy. Our data demonstrate that DM may be an adjuvant therapy with CDDP in solid tumor patients to preserve renal function.

In this study, we investigated the effect of Dendropanax morbifera stem extract (DMS) on streptozotocin (STZ)-induced type 1 diabetic rats. The effect of DMS on memory function was assessed using the Morris water maze test. In addition, we investigated its effect on the microglial activation and subsequent release of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β in the hippocampus. Seven-week-old Wistar rats were exposed to 65 mg/kg STZ by intraperitoneal injection and 100 mg/kg of DMS was administered orally for 30 days. The administration of STZ significantly increased escape latency compared to the control group on all experimental days. Administration of DMS to STZ-treated rats significantly reduced the escape latency. Blood glucose levels significantly increased, while leptin levels significantly decreased in the STZ-treated rats compared to the control group. The administration of DMS to STZ-treated rats significantly ameliorated these changes in the levels of blood glucose and leptin. In addition, administration of DMS significantly increased the serum insulin levels in the STZ-treated rats, not in the control rats. Similarly, STZ treatment increased the morphological changes with hypertrophy of cytoplasm and processes in the hippocampal CA1 region, and significantly increased the levels of pro-inflammatory cytokines such as TNF-α and IL-1β levels in serum and hippocampal homogenates. Administration of DMS to STZ-treated rats significantly reduced the STZ-induced microglial activation and subsequent increase of TNF-α and IL-1β levels in the serum and hippocampal homogenates. These results indicate that DMS could prevent STZ-induced memory impairment by modulating the inflammatory responses in the hippocampus. [ABSTRACT FROM AUTHOR]

Green synthesized silver nanoparticles have significant potential in the pharmaceutical field because of their biological functions such as antioxidant and anticancer activities. Novel silver nanoparticles synthesized from Dendropanax morbifera Léveille leaves (D-AgNPs) exhibit antimicrobial activity and reduce the viability of cancer cells without affecting the viability of RAW 264.7 macrophage-like cells. In this study, we evaluated the anticancer effect of D-AgNPs by measuring the levels of reactive oxygen species (ROS) production and toxicity against A549 and HepG2 cell lines. The effect of D-AgNPs on cell migration, induction of apoptosis, and modification of gene and/or protein expression of cancer-related markers was determined using A549 cells. D-AgNPs exhibited cytotoxicity in A549 and HepG2 cell at different concentrations and enhanced the production of ROS in both cell lines. An increase in cell apoptosis and a reduction in cell migration in A549 cells were also observed after D-AgNP treatment. Furthermore, the effect of D-AgNPs in A549 cells was shown to be related to modification of the EGFR/p38 MAPK pathway. Our data provide the first evidence supporting the potential of D-AgNPs as a possible anticancer agent, particularly for the treatment of non-small cell lung carcinoma. [ABSTRACT FROM AUTHOR]

The ameliorating effects of the ethyl acetate fraction from Dendropanax morbifera (EFDM) on cognitive impairment in high-fat diet (HFD)-induced diabetic mice were examined by measuring its possible pharmacological activities. Administration of EFDM (20 and 50 mg/kg body weight) in HFD-induced diabetic mice significantly improved glucose tolerance status in the intraperitoneal glucose tolerance test (IPGTT). In animal experiments using Y-maze, passive avoidance and Morris water maze tests, the cognitive and behavioral disorders in HFD-induced diabetic mice were considerably recovered by regulating cholinergic systems, including acetylcholine (ACh) levels and acetylcholinesterase (AChE) inhibition, and antioxidant systems, including superoxide dismutase (SOD), glutathione (GSH), oxidized GSH, and malondialdehyde (MDA) levels. Furthermore, HFD-induced abnormal activity of mitochondria were also significantly protected by the improvement of the c-Jun N-terminal protein kinase (JNK) signaling pathway with phosphorylated JNK (p-JNK), phosphorylated insulin receptor substrate (p-IRS), serine/threonine protein kinase (Akt), phosphorylated Akt (p-Akt), and phosphorylated tau (p-tau). Finally, rutin, orientin, isoorientin, and luteolin-7-O-rutinoside as the main phenolics of EFDM were identified using ultra-performance liquid chromatography/quadrupole time of flight tandem mass spectrometry (UPLC-QTOF/MS 2 ). These findings suggest that EFDM may have an effect as a multiple preventive substances to reduce diabetes-associated cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Dendropanax morbifera ( D. morbifera), a species endemic to Korea, is largely distributed throughout the southern part of the country. Its leaves, stems, roots, and seeds have been used as a form of alternative medicine for various diseases and neurological disorders including paralysis, stroke, and migraine. However, the molecular mechanisms that underlie the remedial effects of D. morbifera remain largely unknown. In this paper, extracts from D. morbifera leaves were prepared using ethyl acetate as a solvent (abbreviated as DMLE). The modulatory effects of DMLE on neuroinflammation were studied in a lipopolysaccharide (LPS)-stimulated BV2 murine microglial cell line. Production of pro-inflammatory cytokines, activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-B), and different M1/M2 activation states of microglia were examined. DMLE treatment suppressed the production of pro-inflammatory cytokines including tumor necrosis factor- (TNF-), interleukin-6 (IL-6), and nitric oxide (NO) in LPS-stimulated BV2 cells. DMLE treatment also attenuated the activation of MAPKs and NF-B. In a novel discovery, we found that DMLE up-regulated the marker genes representing an alternative, anti-inflammatory M2 polarization, while suppressing the expression of the classical, pro-inflammatory M1 activation state genes. Here, we uncovered the cellular mechanisms underlying the beneficial effects of D. morbifera against neuroinflammation using BV2 microglia cells. These results strongly suggest that DMLE was able to counter the effects of LPS on BV2 cells via control of microglia polarization states. Additionally, study results indicated that DMLE may have therapeutic potential as a neuroinflammation-suppressing treatment for neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background/Aims: Drug-induced acute kidney injury (AKI) has been a severe threat to hospitalized patients, raising the urgent needs to develop strategies to reduce AKI. We investigated the protective activity of Dendropanax morbifera (DP), a medicinal plant which has been widely used to treat infectious and pain diseases, on acute kidney injury (AKI) using cisplatin-induced nephropathic models. Methods: Both in vitro renal tubular cells (NRK-52E) and in vivo rat models were used to demonstrate the nephroprotective effect of DP. Results: Methanolic extract from DP significantly reduced cisplatin-induced toxicity in renal tubular cells. Through successive liquid extraction, the extract of DP was separated into n-hexane, CHCl3, EtOAc, n-BuOH, and H2O fractions. Among these, the CHCl3 fraction (DPCF) was found to be most potent. The protective activity of DPCF was found to be mediated through anti-oxidant, mitochondrial protective, and anti-apoptotic activities. In in vivo rat models of AKI, treatment with DPCF significantly reversed the cisplatin-induced increase in blood urea nitrogen and serum creatinine and histopathologic damage, recovered the level of anti-oxidant enzymes, and inhibited renal apoptosis. Conclusion: We demonstrated that DP extracts decreased cisplatin-induced renal toxicity, indicating its potential to ameliorate drug-associated acute kidney damage. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]