| Description: |
Dammarenediol II may have the ability to prevent diabetic microvascular complications, including diabetic retinopathy, it can inhibit vascular endothelial growth factor (VEGF)-induced intracellular reactive oxygen species generation and stress fiber formation and vascular endothelial-cadherin disruption. The medicinally important dammarenediol II can be ectopically produced in tobacco, and the production of dammarenediol-II in tobacco plants allows them to adopt a viral defense system. |
| Targets: |
VEGFR | Calcium Channel |
| In vitro: |
| Plant Cell Physiol. 2012 Jan;53(1):173-82. | | Dammarenediol-II production confers TMV tolerance in transgenic tobacco expressing Panax ginseng dammarenediol-II synthase.[Pubmed: 22102695] | Panax ginseng is one of the famous medicinal plants. Ginsenosides, a class of tetracyclic triterpene saponins, are mainly responsible for its pharmacological activity. Most ginsenosides are composed of Dammarenediol II aglycone with various sugar moieties. Dammarenediol II synthase is the first enzyme in the biosynthesis of ginsenosides.
METHODS AND RESULTS:
Here, we report that transgenic tobacco expressing the P. ginseng Dammarenediol II synthase gene (PgDDS) produced Dammarenediol II, and conferred resistance to Tobacco mosaic virus (TMV). Upon infection with TMV, lesions developed more rapidly in transgenic tobacco plants, and their size was smaller than those of wild-type plants. Transgenic tobacco plants showed a low level of both the viral titer and mRNA accumulation of TMV coat protein (CP) compared with the wild type. The production of Dammarenediol II in transgenic tobacco stimulated the expression of tobacco pathogenesis-related genes (PR1 and PR2) under both virus-untreated and -treated conditions. When the leaves of wild-type plants were inoculated with a mixture of TMV and Dammarenediol II, the leaves exhibited a reduced viral concentration and TMV-CP expression than those receiving TMV treatment alone. When the leaves of P. ginseng were infected with TMV, transcription of PgDDS was significantly increased. Transgenic P. ginseng plants harboring a β-glucuronidase (GUS) gene driven by the PgDDS promoter were constructed. The GUS expression was activated when the transgenic ginseng plants were treated with TMV.
CONCLUSIONS:
These results indicate that the medicinally important Dammarenediol II can be ectopically produced in tobacco, and the production of Dammarenediol II in tobacco plants allows them to adopt a viral defense system. |
|
| In vivo: |
| Phytother Res. 2015 Dec;29(12):1910-6. | | Dammarenediol-II Prevents VEGF-Mediated Microvascular Permeability in Diabetic Mice.[Pubmed: 26400610] | Diabetic retinopathy is a major diabetic complication predominantly caused by vascular endothelial growth factor (VEGF)-induced vascular permeability in the retina; however, treatments targeting glycemic control have not been successful.
METHODS AND RESULTS:
Here, we investigated the protective effect of Dammarenediol II, a precursor of triterpenoid saponin biosynthesis, on VEGF-induced vascular leakage using human umbilical vein endothelial cells (HUVECs) and diabetic mice. We overproduced the compound in transgenic tobacco expressing Panax ginseng Dammarenediol II synthase gene and purified using column chromatography. Analysis of the purified compound using a gas chromatography-mass spectrometry system revealed identical retention time and fragmentation pattern to those of authentic standard Dammarenediol II. Dammarenediol II inhibited VEGF-induced intracellular reactive oxygen species generation, but it had no effect on the levels of intracellular Ca(2+) in HUVECs. We also found that Dammarenediol II inhibited VEGF-induced stress fiber formation and vascular endothelial-cadherin disruption, both of which play critical roles in modulating endothelial permeability. Notably, microvascular leakage in the retina of diabetic mice was successfully inhibited by intravitreal Dammarenediol II injection.
CONCLUSIONS:
Our results suggest that the natural drug Dammarenediol II may have the ability to prevent diabetic microvascular complications, including diabetic retinopathy. |
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