Al-Mutary Mohsen G1, Gasem Mohammad Abu-Taweel1, Rajakrishnan Rajagopal2, Kim Sun-Ju3, Hak-Jae Kim4, Young Ock Kim3, Ramzi A Mothana5, Shine Kadaikunnan2, Jamal M Khaled2, Nasir A Siddiqui5, Adnan J Al-Rehaily5. 1. Department of Basic Sciences, College of Education, Imam Abdulrahman Bin Faisal University, P.O. Box 2375, Dammam, 31451, Saudi Arabia. 2. Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia. 3. Department of Bio-Environmental Chemistry, College of Agriculture and Life Sciences, Chungnam National University, 99 Daehak-Ro,Yuseung-Gu, Daejeon 34134, Republic of Korea. 4. Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea. Electronic address: Hak3962@sch.ac.kr. 5. Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Abstract
BACKGROUND: Investigation for a naturally occurring anti-obesity drug has become the need of society all over the world. Betulinic acid (BA) is a lupane-type pentacyclic triterpene and is sourced from various organisms. This high potential biologically active molecule is reported to have anti-obesity effect. In this study, we report the molecular mechanism of action of BA that underlies anti-obesity activity and also an improved method of its isolation common teak tree. METHODS: Mouse pre-adipocyte cells were used to develop hyperlipidemic conditions in vitro. Change in expression of genes associated to adipogenesis was checked using quantitative real-time PCR (qPCR). Co-factor specificity of PPAR gamma was analyzed through immune precipitation and immunoblot. RESULTS: Betulinic acid was found to be effective in reducing the lipid content in 3T3L1 cells. Level of PPAR gamma and LXR alpha was reduced in connection to reduced adipogenesis. Change in steroid responsive co-activators (SRCs) during BA treatment proved that the compound can impart profound change in co-factor selectivity, which is crucial in determining the activity profile of PPAR gamma. BA treatment enhanced the SRC-1 interaction with PPAR gamma while reducing the levels of SRC-3. CONCLUSION: Present study has proved that betulinic acid, a promising candidate in anti-obesity drug development, has potential in regulating the activity of PPAR gamma through co-factor modulation.
BACKGROUND: Investigation for a naturally occurring anti-obesity drug has become the need of society all over the world. Betulinic acid (BA) is a lupane-type pentacyclic triterpene and is sourced from various organisms. This high potential biologically active molecule is reported to have anti-obesity effect. In this study, we report the molecular mechanism of action of BA that underlies anti-obesity activity and also an improved method of its isolation common teak tree. METHODS:Mouse pre-adipocyte cells were used to develop hyperlipidemic conditions in vitro. Change in expression of genes associated to adipogenesis was checked using quantitative real-time PCR (qPCR). Co-factor specificity of PPAR gamma was analyzed through immune precipitation and immunoblot. RESULTS:Betulinic acid was found to be effective in reducing the lipid content in 3T3L1 cells. Level of PPAR gamma and LXR alpha was reduced in connection to reduced adipogenesis. Change in steroid responsive co-activators (SRCs) during BA treatment proved that the compound can impart profound change in co-factor selectivity, which is crucial in determining the activity profile of PPAR gamma. BA treatment enhanced the SRC-1 interaction with PPAR gamma while reducing the levels of SRC-3. CONCLUSION: Present study has proved that betulinic acid, a promising candidate in anti-obesity drug development, has potential in regulating the activity of PPAR gamma through co-factor modulation.
Authors: Sook In Chae; Sang Ah Yi; Ki Hong Nam; Kyoung Jin Park; Jihye Yun; Ki Hyun Kim; Jaecheol Lee; Jeung-Whan Han Journal: Molecules Date: 2020-12-13 Impact factor: 4.411