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Researches on DMY or DHM

2016-8-23

Dihydromyricetin (BSN723 or DMY), also known as ampelopsin, is a flavonoid that has been isolated from a number of plants, including Ampelopsis grossedentata, Cedrus deodara, Hovenia dulcis, and Erythrophleum africanum, that have been used in traditional herbs. Many claims have been made regarding dihydromyricetin’s numerous health benefits including antioxidant properties27, anti-cancer28-30, anti-hypertensive31, anti-inflammatory32, and anti-atherosclerotic effects33. Dihydromyricetin is also indicated as a treatment for alcohol intoxication34 and a preliminary study suggests it as a possible treatment for Alzheimer’s disease35 . A number of published studies provide evidence that dihydromyricetin can protect cells against oxidative injury (for example see, Zhang et al. 200327, Ye et al. 200836, Lin et al. 201437 , Zou et al. 201438). Recently, Jiang et al. (2014)39 examined the effects of dihydromyricetin on oxidative stress and glucose transport activity in a methylglyoxal (MG)-induced PC12 cell line to explore the possibility of using dihydromyricetin for the treatment of MG-induced diabetes-associated cognitive decline. They found that DMY protected PC12 cells against MG-induced apoptosis and glycometabolic disorders, at least in part by restraining the hyperactivation of p-AMPK activity and normalizing the translocation of GLUT4 from the intracellular compartment, resulting in a balance in glucose uptake. Much attention has been focused on the use of dihydromyricetin in the treatment of a variety of cancers and there have been many studies, both in vitro and in vivo, demonstrating inhibitory activity of dihydromyricetin against cell lines of breast cancer40 , liver cancer 29-30,37, melanoma41, osteosarcoma42, and lung cancer43-44. Dihydromyricetin has also shown anticancer activity against bladder cancer45, lung cancer46, and prostate cancer47 xenografts, and showed synergistic effects with adriamycin for treating leukemia xenografts48 . Recently, Chen et al. (2015)49 looked at the effects of dihydromyricetin on nonalcoholic fatty liver disease (NAFLD) in a clinical study. The pathogenesis of NAFLD includes insulin resistance, oxidative stress, mitochondrial dysfunction and inflammation in the liver. The study looked at inflammatory mediators and biomarkers of NAFLD as well as glucose and lipid metabolism. They found that while dihydromyricetin did not alter the severity of fatty infiltration in the liver, it did produce significant improvements in several liver enzymes and reduced serum levels of several markers including tumor necrosis factor-alpha, cytokeratin-18, and fibroblast growth factor 21. They also found that the HOM-IR level was decreased in dihydromyricetin treated patients, but insulin and C-peptide levels were not affected. Levels of low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (Apo B) were also significantly decreased by dihydromyricetin, but the total cholesterol, triglyceride, high-density lipoprotein-cholesterol (HDL-C), and Apo-A-I concentrations did not significantly differ between treated and control groups. Other evidence that dihydromyricetin can affect glucose metabolism include studies that found that DMY activated insulin signaling and increased glucose uptake in skeletal muscle in vitro and in vivo 50,51 . Recent studies have begun to offer clues about dihydromyricetin’s mechanism of action. It is now known that a number of cell signaling pathways are affected by dihydromyricetin. Zou, et al. (2014)38 found that dihydromyricetin fed to rats for 7 days increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1 α) in skeletal muscle. PGC-1α is known to regulate irisin, an exercise-induced myokine that can stimulate the browning of white adipose tissue. In a follow-up study (Zhou, et al., 2015) 5 2 the effect of dihydromyricetin on irisin secretion through the PGC-1 α pathway was investigated in vivo (in rats and humans) and in vitro (L6 myotubes). The results were an increase in irisin secretion with the administration of dihydromyricetin. Dihydromyricetin has also been found to increase the levels of phosphorylated AMP activated protein kinase (AMPK) and Ulk1, and decrease phosphorylated mTOR levels50. The same group also found that dihydromyricetin increased levels of peroxisome proliferator-activated receptor coactivator-1α (PGC-1α ), and Sirt3 in skeletal muscle in vitro and in vivo51 . Jiang, et al. (2014) found that dihydromyricetin ameliorates the oxidative stress response induced by methylglyoxal via the AMPK/GLUT4 signaling pathway39.



NOTES
27.Zhang, YS et al. "Antioxidation properties and mechanism of action of dihydromyricetin from Ampelopsis grossedentata." Acta pharmaceutica Sinica 38.4 (2003): 241-244. 
28.Ni, Feng et al. "Flavonoid ampelopsin inhibits the growth and metastasis of prostate cancer in vitro and in mice." PloS One 7.6 (2012): e38802. 
29.Zhang, Q et al. "Dihydromyricetin promotes hepatocellular carcinoma regression via a p53 activation-dependent mechanism." Scientific reports 4, Article number: 4628 (2014). 
30.Zhang, Q et al. "Dihydromyricetin inhibits migration and invasion of hepatoma cells through regulation of MMP-9 expression." World journal of gastroenterology: WJG 20.29 (2014): 10082. 
31.Lin, Y et al. "Ethanolic extracts and isolated compounds from small-leaf grape (Vitis thunbergii var. taiwaniana) with antihypertensive activities." Journal of agricultural and food chemistry 60.30 (2012): 7435-7441. 
32.Qi, S et al. "Ampelopsin reduces endotoxic inflammation via repressing ROS-mediated activation of PI3K/Akt/NF-κB signaling pathways." International immunopharmacology 12.1 (2012): 278-287. 
33.Chen, Y et al. "Study on the hypolipidemic effect of flavones and dihydromyricetin from Tengcha." Journal of Tea Science 3 (2007): 010. 
34.Shen, Y et al. "Dihydromyricetin as a novel anti-alcohol intoxication medication." The Journal of Neuroscience 32.1 (2012): 390-401. 
35.Liang, J et al. "Dihydromyricetin ameliorates behavioral deficits and reverses neuropathology of transgenic mouse models of Alzheimer's disease." Neurochemical research 39.6 (2014): 1171-1181. 
36.Ye, J et al. "Ampelopsin prevents apoptosis induced by H2O2 in MT-4 lymphocytes." Planta medica 74.3 (2008): 252-257. 
37.Lin, B et al. "A reduction in reactive oxygen species contributes to dihydromyricetin-induced apoptosis in human hepatocellular carcinoma cells." Scientific reports 4, Article number: 7041 (2014). 
38.Zou, D et al. "Dihydromyricetin improves physical performance under simulated high altitude."Medicine and science in sports and exercise 46.11 (2014): 2077-2084. 
39.Jiang, B et al. "Dihydromyricetin ameliorates the oxidative stress response induced by methylglyoxal via the AMPK/GLUT4 signaling pathway in PC12 cells." Brain research bulletin 109 (2014): 117-126. 
40.Fang-Zhen, Z, Xiao-Yuan, Z, and Yong, G. "Anti-proliferation effect of combining dihydromyricetin and adriamycin on MDA-MB-231 cell in vitro." Journal of Hubei University for Nationalities: Medical Edition 27.4 (2010): 4-7. 
41.Zeng, G et al. "Dihydromyricetin induces cell cycle arrest and apoptosis in melanoma SK-MEL-28 cells." Oncology reports 31.6 (2014): 2713-2719. 
42.Zhao, Z et al. "Dihydromyricetin activates AMP-activated protein kinase and P38MAPK exerting antitumor potential in osteosarcoma." Cancer Prevention Research 7.9 (2014): 927-938. 
43.Chen, X et al. "Ampelopsin induces apoptosis by regulating multiple cMyc/S-phase kinase-associated protein 2/F-box and WD repeat containing protein 7/histone deacetylase 2 pathways in human lung adenocarcinoma cells." Molecular medicine reports 11.1 (2015): 105-112. 
44.Jeon, S et al. "Cytotoxic constituents from the bark of Salix hulteni." Archives of pharmacal research 31.8 (2008): 978-982. 
45.Zhang, B et al. "Ampelopsin sodium exhibits antitumor effects against bladder carcinoma in orthotopic xenograft models." Anti-cancer drugs 23.6 (2012): 590-596. 
46.Zeng, S et al. "Anti-tumor effects of ampelopsin on human lung cancer GLC-82 implanted in nude mice." Journal of Chinese medicinal materials 27.11 (2004): 842-845. 
47.Ni, F et al. "Flavonoid ampelopsin inhibits the growth and metastasis of prostate cancer in vitro and in mice." PloS One 7.6 (2012): e38802. 
48.Zhu, H et al. "Dihydromyricetin prevents cardiotoxicity and enhances anticancer activity induced by adriamycin." Oncotarget 6.5 (2015): 3254. 
49.Chen, S et al. "Dihydromyricetin improves glucose and lipid metabolism and exerts anti-inflammatory effects in nonalcoholic fatty liver disease: a randomized controlled trial." Pharmacological Research (2015). 
50.Shi, L et al. "Dihydromyricetin improves skeletal muscle insulin resistance by inducing autophagy via the AMPK signaling pathway." Molecular and cellular endocrinology 409 (2015): 92-102. 
51.Shi, L et al. "Dihydromyricetin improves skeletal muscle insulin sensitivity by inducing autophagy via the AMPK-PGC-1α-Sirt3 signaling pathway." Endocrine (2015): 1-12. 
52.Zhou, Q et al. "Dihydromyricetin stimulates irisin secretion partially via the PGC-1α- pathway." Molecular and cellular endocrinology 412 (2015): 349-357. 53. Metts, B et al. "DDDAS design of drug.
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