In Vivo Hypoglycemic Effects, Potential Mechanisms and LC-MS/MS Analysis of Dendropanax Trifidus Sap Extract

Abstract

Extracts of medicinal plants have been widely used to benefit human health. Dendropanax morbiferus (DM) has been well-studied for its anti-inflammatory and anti-oxidative effects, while Dendropanax trifidus (DT) is a lesser-known ecotype phylogenetically similar to DM, which has received significantly less attention. Studies thus far have primarily focused on leaf and bark extracts of DM, and not much is yet known about the properties of either DM or DT sap. Therefore, here we performed in vivo toxicity and efficacy studies, in order to assess the biological effects of DT sap. To establish a safe dosage range, single dose or two-week daily administrations of various concentrations were performed for ICR mice. Measurements of survival ratio, body/organ weight, blood chemistry, histochemistry and Western blots were performed. A concentration of ≤0.5 mg/g DT sap was found to be safe for long-term administration. Interestingly, DT sap significantly reduced blood glucose in female mice. In addition, increasing concentrations of DT sap decreased phosphorylated (p) insulin receptor substrate (IRS)-1(ser1101)/IRS-1 in liver tissues, while increasing pAMP-activated protein kinase (AMPK)/AMPK in both the liver and spleen. To analyze its components, liquid chromatography-tandem mass spectrometry of DT sap was performed in comparison with Acer saccharum (AS) sap. Components such as estradiol, trenbolone, farnesol, dienogest, 2-hydroxyestradiol and linoleic acid were found to be highly enriched in DT sap compared to AS sap. Our results indicate DT sap exhibits hypoglycemic effects, which may be due to the abundance of the bioactive components.

Dendropanax trifidus Sap-Mediated Suppression of Obese Mouse Body Weight and the Metabolic Changes Related with Estrogen Receptor Alpha and AMPK-ACC Pathways in Muscle Cells

“…In our previous study, DT sap was compared with Acer Saccharum (AS) sap using liquid chromatograph-tandem mass spectrometer, and we observed that estradiol was abundantly contained in DT sap compared to AS sap [ 25 ]. We were interested in knowing if estrogen may be an active component in DT sap-mediated signaling, thus we utilized human ERα-HeLa-9903 cell lines which contain a luciferase reporter gene at downstream of an estrogen responsive promoter element.…”

“…In our previous report, we identified estrogen as one of the major components of DT sap [ 25 ]. In this study, we found that DT sap can signal through estrogen receptor alpha ( Figure 4 A).…”

“…Dendropanax trifidus sap was ethanol-extracted, freeze-dried and stored at −20 °C. For experiments, the freeze-dried final product was dissolved in EtOH and diluted with water or medium [ 25 ].…”

“…Makino ex H.Hara from Simasi, Mieken, Japan was registered at Ibaraki Nature Museum (INM-2-212778). Dendropanax trifidus sap was ethanol-extracted, freeze-dried and stored at −20 • C. For experiments, the freeze-dried final product was dissolved in EtOH and diluted with water or medium [25].…”

“…We further examined the effects of DT sap on glycolysis and mitochondrial respiration parameters in C2C12 skeletal muscle cells. To study the underlying molecular mechanism, we examined whether the function of DT sap is mediated by estrogen receptor, as estrogen was one of the major components of DT sap [ 25 ]. Finally, we show here AMPK and its downstream signaling—including ACC and PFKFB3 which are significantly altered by DT sap treatment, implying that those cellular components might mediate glycolytic and metabolic changes within the cell, thus contributing to weight loss in mice treated with DT sap.…”