Yi-Ching Lo has her expertise in drug development and in improving the aging health. Her research interest is focusing on the development of neuroprotective and muscle enhancing agents, including chemical and natural products.
Liuwei dihuang (LWDH) is a widely used traditional Chinese medicine for neurosis, diabetics and renal disorders. Methylglyoxal (MG) is the most potent precursor of advanced glycation end products, which has been implicated in diabetic complications, cardiovascular diseases and central nervous system disorders. The present study aimed to investigate the protective effects of LWDH on MG-induced myotoxicity in C2C12 myotubes. Methods: C2C12 myoblasts were differentiated by differentiation medium to form myotube structure. C2C12 myotubes were then pre-treated with LWDH water extract (LWDH-WE) for 1 h before MG treatment. Protein expressions were analyzed by western blot analysis. Morphological changes were observed by an inverted microscope. Mitochondria membrane potential and reactive oxygen species (ROS) production were measured by flow cytometer using JC-1 staining and H2DCF-DA staining, respectively. Results: In C2C12 myotubes, LWDH-WE attenuated MG-induced reduction of mitochondrial membrane potential. Moreover, MG-induced NADPH oxidase (Nox) activation and ROS production were inhibited by LWDH-WE treatment. Furthermore, LWDH-WE attenuated MG-induced myotubes atrophy accompanied with down-regulating signaling of protein degradation pathway including Foxo3a, atrogin-1 and MuRF-1 in C2C12 cells. Conclusion. LWDH might provide protection against MG-induced myotoxicity via attenuating oxidative stress and protein degradation in C2C12 myotubes, suggesting the potential benefits of LWDH on treatment of skeletal muscle atrophy.
Tetsuo Narumi studied organometallic chemistry at Waseda University in Shinjuku, Tokyo, where he worked in the research group of Prof. Isao Shimizu. After PhD studies at Waseda University with Prof. Shimizu followed by Kyoto University with Prof. Nobutaka Fujii, he spent a year in US as a JSPS postdoctoral fellow with Prof. Jeffrey W. Bode at the University of Pennsylvania. In 2009, he began his academic career in Japan, at Tokyo Medical and Dental University with Prof. Hirokazu Tamamura. In 2013, he began his independent career at Shizuoka University, in Japan, as a associate professor in the Bioorganic Chemistry.
Naturally occurring pentacyclic triterpenoid derivatives, such as betulinic acid derivatives, have been shown to exhibit various biological activities including anti-HIV activity. IC9564 [Mayaux, JF. Et al, PNAS. 1994] and RPR103611 [Dereu, N. et al., JMC, 1996] are statin derivatives of betulinic acid tethered by 8-aminooctanoic acid linker, which was reported as a novel class of HIV-1 entry inhibitors. Although those betulinic acid derivatives show nanomolar order potency agains diverse HIV-1 strains, relatively high cytotoxicity is one of the drawbacks of them. In this study, the structure-activity relationship study of a series of triterpenoid derivatives was conducted to identify the potential triterpenoid-based HIV entry inhibitors with lower cytotoxicity than betulinic acid derivatives. Significant potency gains were made by replacing the betulinic acid moiety with the oleanoic acid, resulting in the discovery of several potent compounds. This study identified a novel lead compound OKS3-019 with significant anti-HIV activity against 89.6 strain of HIV-1 and lower cytotoxicity than those of known betulinic acid derivatives. Design, syntheses, bioevaluation and docking models of the newly identified oleanoic acid derivatives will be discussed.