|Wu, Jie - Guangzhou University|
|Li, Xue - Guangzhou University|
|Wan, Wencheng - Guangzhou University|
|Yang, Qiaohong - Guangzhou University|
|Ma, Weifeng - Guangzhou University|
|Chen, Dan - Guangzhou University|
|Hu, Jiangmiao - Chinese Academy Of Sciences|
|Chen, Cheng-yen - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Wei, Xiaoyong - Guangzhou University|
Submitted to: Journal of Ethnopharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/15/2017
Publication Date: 1/16/2017
Citation: Wu, J., Li, X., Wan, W., Yang, Q., Ma, W., Chen, D., Hu, J., Chen, C., Wei, X. 2017. Gigantol from Dendrobium chrysotoxum Lindl. binds and inhibits aldose reductase gene to exert its anti-cataract activity: an in vitro mechanistic study. Journal of Ethnopharmacology. 198:255-261. https://doi.org/10.1016/j.jep.2017.01.026.
DOI: https://doi.org/10.1016/j.jep.2017.01.026 Interpretive Summary: Cataracts are a major cause of blindness in patients with diabetes. While the development and progression of diabetic cataracts are caused by many mechanisms, the polyol pathway has been recognized as one of the most important mechanisms. Aldose reductase is a rate-limiting enzyme in this pathway, and its expression is induced by high blood glucose. The product of this enzyme, sorbitol, increases osmotic pressure, changes cell membrane permeability, and promotes the development of cataracts. Dendrobium chrysotoxum is mainly used in Chinese medicine to treat sweating, stomachaches, and vision problems. While the therapeutic potential of Dendrobium chrysotoxum for vision may be attributed to an additive/synergistic effect of many compounds in the plant, the compound gigantol may protect against diabetic cataracts by inhibiting aldose reductase activity. In a cell culture experiment using human lens epithelial cells, we found that gigantol extracted from Dendrobium chrysotoxum suppressed the gene expression of aldose reductase by inserting itself into the DNA base pairs of the aldose reductase gene. These findings provide a theoretical basis for the development of Dendrobium chrysotoxum for the treatment of diabetic cataracts.
Technical Abstract: Ethnopharmacological relevance: Dendrobium. chrysotoxum Lindl is a commonly used species of medicinal Dendrobium which belongs to the family of Orchidaceae, locally known as Shihu or Huangcao. D. chrysotoxum Lindl is widely known for medicinal values in traditional Chinese medicine as it possesses antiinflammatory, anti-hyperglycemic induction, antitumor and antioxidant properties. Study aim: To characterize the interaction between gigantol extracted from D. chrysotoxum Lindl and the AR gene, and determine gigantol efficacy against cataractogenesis. Materials and methods: Human lens epithelial cells (HLECs) were induced by glucose as the model group. Reverse transcription polymerase chain reaction (RT-PCR) was used to assess AR gene expression. Then, the mode of interaction of gigantol with the AR gene was evaluated by UV-visible spectroscopy, atomic force microscope (AFM) and surface-enhanced Raman spectroscopy (SERS). The binding constant was determined by UV-visible. Results: Gigantol depressed AR gene expression in HLECs. UV-visible spectra preliminarily indicated that interaction between the AR gene and gigantol may follow the groove mode, with a binding constant of 1.85 x 10(3) L/mol. Atomic force microscope (AFM) data indicated that gigantol possibly bound to insert AR gene base pairs of the double helix. Surface-enhanced Raman spectroscopy (SERS) studies further supported these observations. Conclusion: Gigantol extracted from D. chrysotoxum Lindl not only has inhibitory effects on aldose reductase, but also inhibits AR gene expression. These findings provide a more comprehensive theoretical basis for the use of Dendrobium for the treatment of diabetic cataract.