DW1029M, a novel botanical drug candidate, inhibits advanced glycation end-product formation, rat lens aldose reductase activity, and TGF-β1 signaling.
DW1029M is a botanical extract consisting of Morus bark and Puerariae radix, produced by Dong-Wha Pharmaceutical, for nephroprotective drug development; it has been in phase II clinical trials in Korea. In our mechanistic investigations, we found that DW1029M inhibits advanced glycation end products (AGEs), rat lens aldose reductase (RLAR), and transforming growth factor (TGF)-β1 signaling, all of which are implicated in diabetic complications such as diabetic nephropathy and diabetic retinopathy. DW1029M inhibits AGE formation via Fe(2+) chelation. The extract contains 13 active constituents that inhibit AGE formation, 8 active constituents that inhibit RLAR activity, and 1 inhibitor of TGF-β1 signaling. Our results suggest DW1029M protects against diabetic nephropathy via blockade of AGE formation, RLAR activity, and TGF-β1 signaling.
Department of Research and Development, Dong-Wha Pharmaceutical Company, Giheung Gu, Yong-In City, Republic of Korea; School of Biological Sciences, Seoul National University, Seoul, Republic of Korea; and.
Joobyoung
J
Yoon
Department of Research and Development, Dong-Wha Pharmaceutical Company, Giheung Gu, Yong-In City, Republic of Korea;
Hyunyong
H
Lee
Department of Research and Development, Dong-Wha Pharmaceutical Company, Giheung Gu, Yong-In City, Republic of Korea;
Hwan Bong
HB
Chang
Department of Research and Development, Dong-Wha Pharmaceutical Company, Giheung Gu, Yong-In City, Republic of Korea;
Hyunsik
H
Choi
Department of Research and Development, Dong-Wha Pharmaceutical Company, Giheung Gu, Yong-In City, Republic of Korea;
Yong Sung
YS
Kim
Department of Research and Development, Dong-Wha Pharmaceutical Company, Giheung Gu, Yong-In City, Republic of Korea;
Yang Kook
YK
Rho
Department of Research and Development, Dong-Wha Pharmaceutical Company, Giheung Gu, Yong-In City, Republic of Korea;
Seungkyoo
S
Seong
GyeongGi Bio Center, Youngtong Gu, Suwong City, Republic of Korea.
Dong Hwa
DH
Choi
School of Biological Sciences, Seoul National University, Seoul, Republic of Korea; and.
Dongeun
D
Park
Department of Research and Development, Dong-Wha Pharmaceutical Company, Giheung Gu, Yong-In City, Republic of Korea; bottle9@daum.net.
Bonchul
B
Ku
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000517:prevention & control; D003930:Diabetic Retinopathy / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000201:enzymology; D031625:Morus; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D029908:Pueraria; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013311:Streptozocin / Q000009:adverse effects; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism
D017127:Glycation End Products, Advanced; D010936:Plant Extracts; D053773:Transforming Growth Factor beta1; D013311:Streptozocin; D000449:Aldehyde Reductase
advanced glycation end products; aldose reductase; diabetes; diabetic complication; nephropathy; reactive oxygen species; transforming growth factor-β1