Anti-diabetic effects of aqueous extract of Dendropanax morbifera Lev. leaves in streptozotocin-induced diabetic Sprague-Dawley rats

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.

Dendropanoxide, a Triterpenoid from Dendropanax morbifera, Ameliorates Hepatic Fibrosis by Inhibiting Activation of Hepatic Stellate Cells through Autophagy Inhibition

Hepatic fibrosis results from chronic liver damage and is characterized by excessive accumulation of extracellular matrix (ECM). In this study, we showed that dendropanoxide (DPX), isolated from Dendropanax morbifera, had anti-fibrotic effects on hepatic fibrosis by inhibiting hepatic stellate cell (HSC) activation. DPX suppressed mRNA and protein expression of α-SMA, fibronectin, and collagen in activated HSCs. Moreover, DPX (40 mg/kg) treatment significantly lowered levels of liver injury markers (aspartate aminotransferase and alanine transaminase), expression of fibrotic markers, and deposition of ECM in a carbon tetrachloride-induced mouse model. Anti-fibrotic effects of DPX were comparable to those of silymarin in a hepatic fibrosis mouse model. As a possible mechanism of anti-fibrotic effects, we showed that DPX inhibited autophagosome formation (LC3B-II) and degradation of p62, which have important roles in HSC activation. These findings suggest that DPX inhibits HSC activation by inhibiting autophagy and can be utilized in hepatic fibrosis therapy.

Optimization of Caffeic Acid Extraction from Dendropanax morbifera Leaves Using Response Surface Methodology and Determination of Polyphenols and Antioxidant Properties

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.

Antihyperuricemic Effect of Dendropanax morbifera Leaf Extract in Rodent Models

Dendropanax morbifera is a well-known traditional medicine used in China and Korea to treat intestinal disorders, urosis, diuresis, and chronic glomerulonephritis. Hyperuricemia is a metabolic disorder characterized by a high uric acid level in serum due to an imbalance between uric acid production and excretion and causes gout. Recently, the prevalence of hyperuricemia worldwide has been continuously increasing. Xanthine oxidase (XOD) inhibitors (allopurinol (ALP) and febuxostat) and uricosuric agents (benzbromarone and probenecid) are used to treat hyperuricemia clinically. However, because these drugs are poorly tolerated and cause side effects, such as kidney diseases, hepatotoxicity, gastrointestinal symptoms, and hypersensitivity syndrome, only a limited number of drugs are available. We investigated the antihyperuricemic effects of Dendropanax morbifera leaf ethanol extract (DMLE) and its underlying mechanisms of action through in vitro and in vivo studies. We evaluated uric acid levels in serum and urine, and xanthine oxidase (XOD) inhibition activity in the serum and liver tissue of a hyperuricemic rat model of potassium oxonate (PO)-induced hyperuricemic rats. In vitro study, XOD-inhibitory activity was the lowest among the test substances at the IC50 of ALP. However, the IC50 of DMLE-70 was significantly low compared with that of other DMLEs ( p < 0.05 ). In PO-induced hyperuricemic rats, uric acid (UA) levels in serum and urine were significantly reduced in all DMLE-70 and allopurinol-treated (ALT) groups than in the PC group ( p < 0.05 ). UA levels in urine were lower than those in serum in all DME groups. In PO-induced hyperuricemic rats, DMEE-200 reduced UA concentration in serum and increased UA excretion in the urine. These findings suggest that DMLE exerts antihyperuricemic and uricosuric effects on promoting UA excretion by enhanced secretion and inhibition of UA reabsorption in the kidneys. Thus, DMLE may be a potential treatment for hyperuricemia and gout.

In Vivo Evaluation of Dendropanax morbifera Leaf Extract for Anti-Obesity and Cholesterol-Lowering Activity in Mice

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.

Synergistic Protection by Isoquercitrin and Quercetin against Glutamate-Induced Oxidative Cell Death in HT22 Cells via Activating Nrf2 and HO-1 Signaling Pathway: Neuroprotective Principles and Mechanisms of Dendropanax morbifera Leaves

Dendropanax morbifera leaves (DML) have long been used as traditional medicine to treat diverse symptoms in Korea. Ethyl acetate-soluble extracts of DML (DMLE) rescued HT22 mouse hippocampal neuronal cells from glutamate (Glu)-induced oxidative cell death; however, the protective compounds and mechanisms remain unknown. Here, we aimed to identify the neuroprotective ingredients and mechanisms of DMLE in the Glu-HT22 cell model. Five antioxidant compounds were isolated from DMLE and characterized as chlorogenic acid, hyperoside, isoquercitrin, quercetin, and rutin by spectroscopic methods. Isoquercitrin and quercetin significantly inhibited Glu-induced oxidative cell death by restoring intracellular reactive oxygen species (ROS) levels and mitochondrial superoxide generation, Ca2+ dysregulation, mitochondrial dysfunction, and nuclear translocation of apoptosis-inducing factor. These two compounds significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the presence or absence of Glu treatment. Combinatorial treatment of the five compounds based on the equivalent concentrations in DMLE showed that significant protection was found only in the cells cotreated with isoquercitrin and quercetin, both of whom showed prominent synergism, as assessed by drug–drug interaction analysis. These findings suggest that isoquercitrin and quercetin are the active principles representing the protective effects of DMLE, and these effects were mediated by the Nrf2/HO-1 pathway.

Enhanced Antiobesity Efficacy of Tryptophan Using the Nanoformulation of Dendropanax morbifera Extract Mediated with ZnO Nanoparticle

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.