Dioscin CAS NO.19057-60-4

Potent anti-inflammatory effect of dioscin mediated by suppression of TNF-α-induced VCAM-1, ICAM-1and EL expression via the NF-κB pathway.[Pubmed: 25577996]

Biochimie. 2015 Mar;110:62-72.

The modulation of adhesion molecule expression and the reduction of aberrant leukocyte adhesion to the endothelium are attractive approaches for treating inflammation-related vascular complications, including atherosclerosis. Dioscin has a variety of biological activities including anti-inflammatory activity. However, the molecular mechanisms behind Dioscin's anti-inflammatory effects are not fully understood.
METHODS AND RESULTS:
In this study, we investigated the molecular mechanism involved in the effects of Dioscin on inflammatory mediators in tumor necrosis factor-α (TNF-α)-stimulated human umbilical vein endothelial cells (HUVECs). In vitro, Dioscin decreased monocyte adhesion to TNF-α-treated HUVECs by reducing vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) expression and inhibiting endothelial lipase (EL) expression in TNF-α-treated HUVECs and macrophages by blocking the nuclear factor-κB (NF-κB) pathway.
CONCLUSIONS:
Thus, Dioscin might inhibit inflammation by interrupting the NF-κB signaling pathway and could potentially contribute to treatments for inflammatory diseases and atherosclerosis.

Dioscin restores the activity of the anticancer agent adriamycin in multidrug-resistant human leukemia K562/adriamycin cells by down-regulating MDR1 via a mechanism involving NF-κB signaling inhibition.[Pubmed: 23621869 ]

J Nat Prod. 2013 May 24;76(5):909-14.

The purpose of this study was to investigate the ameliorating effect of Dioscin (1) on multidrug resistance (MDR) in adriamycin (ADR)-resistant erythroleukemic cells (K562/adriamycin, K562/ADR) and to clarify the molecular mechanisms involved.
METHODS AND RESULTS:
High levels of multidrug resistance 1 (MDR1) mRNA and protein and reduced ADR retention were found in K562/ADR cells compared with parental cells (K562). Dioscin (1), a constituent of plants in the genus Discorea, significantly inhibited MDR1 mRNA and protein expression and MDR1 promoter and nuclear factor κ-B (NF-κB) activity in K562/ADR cells. MDR1 mRNA and protein suppression resulted in the subsequent recovery of intracellular drug accumulation. Additionally, inhibitor κB-α (IκB-α) degradation was inhibited by 1. Dioscin (1) reversed ADR-induced MDR by down-regulating MDR1 expression by a mechanism that involves the inhibition of the NF-κB signaling pathway.
CONCLUSIONS:
These findings provide evidence to support the further investigation of the clinical application of Dioscin (1) as a chemotherapy adjuvant.

Dioscin ameliorates cerebral ischemia/reperfusion injury through the downregulation of TLR4 signaling via HMGB-1 inhibition.[Pubmed: 25772012]

Free Radic Biol Med. 2015 Mar 12.

We previously reported the promising effect of Dioscin against hepatic ischemia/reperfusion (I/R) injury, but its effect on cerebral I/R injury remains unknown.
METHODS AND RESULTS:
In this work, an in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) model and an in vivo middle cerebral artery occlusion (MCAO) model were used. The results indicated that Dioscin clearly protected PC12 cells and primary cortical neurons against OGD/R insult and significantly prevented cerebral I/R injury. Further research demonstrated that Dioscin-induced neuroprotection was accompanied by a significant inhibition in the expression and the nuclear to cytosolic translocation of HMGB-1, reflected by decreased TLR4 expression. Blockade of the TLR4/MyD88/TRAF6 signaling pathway by Dioscin inhibited NF-κB and AP-1 transcriptional activities, MAPK and STAT3 phosphorylation, and pro-inflammatory cytokine responses, and upregulated the levels of anti-inflammatory factors. In addition, small interfering RNA (siRNA) and overexpressed genes of HMGB-1 and TLR4 were applied in in vitro experiments, respectively, and the results further confirmed that Dioscin showed an efficient neuroprotection because of its inhibiting effects on HMGB-1/TLR4 signaling and subsequent suppressing inflammation.
CONCLUSIONS:
These findings provide new insights that will aid in elucidating the effect of Dioscin against cerebral I/R injury and support the development of Dioscin as a potential treatment for ischemic stroke.

Dioscin inhibits colon tumor growth and tumor angiogenesis through regulating VEGFR2 and AKT/MAPK signaling pathways.[Pubmed: 25111127]

Dioscin inhibits adipogenesis through the AMPK/MAPK pathway in 3T3-L1 cells and modulates fat accumulation in obese mice.[Pubmed: 25189808]

Int J Mol Med. 2014 Nov;34(5):1401-8.

Dioscin (DS) is a steroidal saponin present in a number of medicinal plants and has been shown to exert anticancer, antifungal and antiviral effects. The present study aimed to deternube the effects DS on the regulation of adipogenesis and to elucidate the underlying mechanisms.
METHODS AND RESULTS:
In vitro experiments were performed using differentiating 3T3-L1 cells treated with various concentrations (0-4 μM) of DS for 6 days. A cell viability assay was performed on differentiating cells following exposure to DS. Oil Red O staining and triglyceride content assay were performed to evaluate the lipid accumulation in the cells. We also carried out the following experiments: i) flow cytometry for cell cycle analysis, ii) quantitative reverse transcription polymerase chain reaction for measuring adipogenesis-related gene expression, and iii) western blot analysis to measure the expression of adipogenesis transcription factors and AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC) and mitogen-activated protein kinase (MAPK) phosphorylation. In vivo experiements were performed using mice with obesity induced by a high-fat diet (HFD) that were treated with or without DS for 7 weeks. DS suppressed lipid accumulation in the 3T3-L1 cells without affecting viability at a dose of up to 4 μM. It also delayed cell cycle progression 48 h after the initiation of adipogenesis. DS inhibited adipocyte differentiation by the downregulation of adipogenic transcription factors and attenuated the expression of adipogenesis-associated genes. In addition, it enhanced the phosphorylation of AMPK and its target molecule, ACC, during the differentiation of the cells. Moreover, the inhibition of adipogenesis by DS was mediated through the suppression of the phosphorylation of MAPKs, such as extracellular-regulated kinase 1/2 (ERK1/2) and p38, but not c-Jun-N-terminal kinase (JNK). DS significantly reduced weight gain in the mice with HFD-induced obesity; this was evident by the suppression of fat accumulation in the abdomen.
CONCLUSIONS:
The present study reveals an anti-adipogenic effect of DS in vitro and in vivo and highlights AMPK/MAPK signaling as targets for DS during adipogenesis.

Toxicol Appl Pharmacol. 2014 Dec 1;281(2):166-73.

Dioscin has shown cytotoxicity against cancer cells, but its in vivo effects and the mechanisms have not elucidated yet. The purpose of the current study was to assess the antitumor effects and the molecular mechanisms of Dioscin.
METHODS AND RESULTS:
We showed that Dioscin could inhibit tumor growth in vivo and has no toxicity at the test condition. The growth suppression was accompanied by obvious blood vessel decrease within solid tumors. We also found Dioscin treatment inhibited the proliferation of cancer and endothelial cell lines, and most sensitive to primary cultured human umbilical vein endothelial cells (HUVECs). What's more, analysis of HUVECs migration, invasion, and tube formation exhibited that Dioscin has significantly inhibitive effects to these actions. Further analysis of blood vessel formation in the matrigel plugs indicated that Dioscin could inhibit VEGF-induced blood vessel formation in vivo. We also identified that Dioscin could suppress the downstream protein kinases of VEGFR2, including Src, FAK, AKT and Erk1/2, accompanied by the increase of phosphorylated P38MAPK.
CONCLUSIONS:
The results potently suggest that Dioscin may be a potential anticancer drug, which efficiently inhibits angiogenesis induced by VEGFR2 signaling pathway as well as AKT/MAPK pathways.

Anti-hyperuricemic and nephroprotective effects of Rhizoma Dioscoreae septemlobae extracts and its main component dioscin via regulation of mOAT1, mURAT1 and mOCT2 in hypertensive mice.[Pubmed: 24866061 ]

Arch Pharm Res. 2014 Oct;37(10):1336-44.

Rhizoma Dioscoreae septemlobae (RDSE) has been widely used for the treatment of hyperuricemia in China. However, the therapeutic mechanism has been unknown.
METHODS AND RESULTS:
This study investigated the antihyperuricemic mechanisms of the extracts obtained from RDSE and its main component Dioscin (DIS) in hyperuricemic mice. Hyperuricemic mice were induced by potassium oxonate (250 mg/kg). RDSE or DIS was orally administered to hyperuricemic mice at dosages of 319.22, 638.43, 1276.86 mg/kg/day for 10 days, respectively. Uric acid or creatinine in serum and urine was determined by HPLC or HPLC-MS/MS, respectively. The xanthine oxidase (XO) activities in mice liver were examined in vitro. Protein levels of organic anion transporter 1 (mOAT1), urate transporter 1 (mURAT1) and organic cation transporter 2 (mOCT2) in the kidney were analyzed by western blotting. The results indicated that uric acid and creatinine in serum were significantly increased by potassium oxonate, as compared to that of control mice. Compared saline-treated group, after RDSE treatment in the high and middle dose, the expression of mOAT1 increased 47.98 and 54.48 %, respectively, which accompanied with the decreased expression of mURAT1 (47.63 %) in high dose. After DIS treatment in high, middle and low dose, the expression of mOAT1 increased 23.93, 32.80 and 25.28 % compared to saline-treated group, respectively, which accompanied with the decreased expression of mURAT1 (51.07, 51.42 and 51.35 %). However, RDSE and DIS displayed a weak XO inhibition activity compared with allopurinol.
CONCLUSIONS:
Therefore, RDSE and DIS processed uricosuric and nephroprotective actions by regulation of mOAT1, mURAT1 and mOCT2.