Review
Biochemistry & Molecular Biology
Hiroyuki Miyachi
Summary: Recent progress in understanding the structure and pharmacology of hPPAR gamma has allowed for investigation of various ligands and their effects on biological responses. These ligands serve as valuable tools for studying hPPAR gamma function and potential drugs for hPPAR gamma-related diseases. This review summarizes the medicinal chemistry research on the design, synthesis, and evaluation of hPPAR gamma antagonists based on the induction/inhibition concept of helix 12 (H12) and presents X-ray crystallographic analyses of their unique binding modes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Iason Psilopatis, Kleio Vrettou, Constantinos Troungos, Stamatios Theocharis
Summary: Endometrial carcinoma is the most common malignant tumor of the female genital tract in the United States. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptor proteins which regulate gene expression. In our literature review of 27 relevant studies published between 2000 and 2023, it was found that PPAR alpha and PPAR beta/delta isoforms were upregulated in endometrial cancer cells, while PPAR gamma levels were significantly lower. Interestingly, PPAR agonists were found to be potent anti-cancer therapeutic alternatives. Overall, PPARs seem to play a significant role in endometrial cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Marjolein Garsen, Baranca Buijsers, Marloes Sol, Lena Gockeln, Ramon Sonneveld, Toin H. van Kuppevelt, Mark de Graaf, Jacob van den Born, Jan A. A. M. Kamps, Daniel H. van Raalte, Rutger W. van der Meer, Hildo J. Lamb, Jan-Luuk Hillebrands, Ton J. Rabelink, Marissa L. Maciej-Hulme, Guido Krenning, Tom Nijenhuis, Johan van der Vlag
Summary: PPAR y agonists can ameliorate proteinuria by inhibiting the expression of glomerular HPSE, providing a potential mechanism for the renoprotective effects of these drugs.
Article
Biochemistry & Molecular Biology
Hyejin Ko, Hongjun Jang, Seungchan An, In Guk Park, Sungjin Ahn, Junpyo Gong, Seok Young Hwang, Soyeon Oh, Soo Yeon Kwak, Won Jun Choi, Hyoungsu Kim, Minsoo Noh
Summary: The upregulation of adiponectin production is a potential therapeutic strategy for metabolic diseases. Galangin and its derivatives were found to promote adiponectin synthesis by binding to PPARγ and enhancing its activity while reducing the activity of ERβ. A novel galangin derivative, galangin 3-benzyl-5,7-dimethylether, showed the highest potency and selectively bound to PPARγ, suggesting its potential therapeutic use in various metabolic diseases.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Chang Wang, Fei Peng, Bohua Zhong, Ying Shi, Xiaomei Wang, Xueyuan Jin, Junqi Niu
Summary: The study showed that MBT1805 has therapeutic effects on ANIT-induced cholestasis, improving abnormal biochemical indicators, gallbladder enlargement, and histopathological changes. By regulating bile acid synthesis, biotransformation, and transport, MBT1805 helps relieve cholestasis.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yanhao Qiu, Mailin Gan, Xingyu Wang, Tianci Liao, Qiuyang Chen, Yuhang Lei, Lei Chen, Jinyong Wang, Ye Zhao, Lili Niu, Yan Wang, Shunhua Zhang, Li Zhu, Linyuan Shen
Summary: Excessive expansion of adipocytes can lead to ectopic fat deposition, increasing the risk of metabolic diseases. Peroxisome proliferator-activated receptor gamma (PPARγ) plays a crucial role in fat cell differentiation and adipogenesis.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Mahesha Gangadhariah, Triveni Pardhi, Jahnavi Ravilla, Subhash Chandra, Sridevi Annapurna Singh
Summary: PPAR gamma agonists are effective in treating type 2 diabetes but have severe side effects. Lemon contains eriocitrin, which may have potential as a PPAR gamma agonist.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Multidisciplinary
Jie Yang, Xiao Yang, Yi-fei Zhang, Jia-ning Tian, Shi-cheng Fan, Yue Gao, Hui-lin Li, Cheng-hui Cai, Min Huang, Hui-chang Bi
Summary: In this study, it was found that activation of PPARa leads to hepatomegaly in mice, with hepatocyte hypertrophy around the central vein area and hepatocyte proliferation around the portal vein area. The study also revealed that the upregulation of PPARa targets is higher in the central vein area compared to the portal vein area, while the upregulation of proliferation-related proteins mainly occurs in the portal vein area. These findings provide new insights into the understanding of PPARa activation-induced liver enlargement and regeneration.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Neurosciences
Riham M. Mansour, Nesrine S. El Sayed, Maha A. E. Ahmed, Ayman E. El-Sahar
Summary: This study aimed to explore the neuroprotective effect of telmisartan in 3-nitropropionic acid-induced neurotoxicity. The results showed that telmisartan improved motor and cognitive functioning, reduced neuronal inflammation and apoptosis, and promoted mitochondrial biogenesis through PPAR gamma activation.
MOLECULAR NEUROBIOLOGY
(2022)
Review
Cell Biology
Iason Psilopatis, Kleio Vrettou, Florian Nima Fleckenstein, Stamatios Theocharis
Summary: Preeclampsia is a common hypertensive disorder in pregnancy, and PPARs play a significant role in its pathophysiology. Studies have shown contradictory conclusions regarding PPAR expression in preeclamptic placentae, but PPAR gamma agonists have been identified as a novel and potent anti-preeclamptic treatment option.
Review
Pharmacology & Pharmacy
Lara Senn, Anna-Maria Costa, Rossella Avallone, Katarzyna Socala, Piotr Wlaz, Giuseppe Biagini
Summary: The peroxisome proliferator-activated receptor gamma (PPAR gamma), known for its role in metabolic disorders, has been increasingly investigated for its potential involvement in neurological diseases, particularly in epilepsy. Epilepsy, a chronic neurological disorder, has a significant impact on patients' psychological, social, and economic well-being. With a global prevalence of 0.5%-1.0%, epilepsy ranks fourth in importance among neurological disorders. This review focuses on recent findings regarding the intracellular processes dependent on PPAR gamma and their potential anti-seizure effects, as well as promising results from clinical investigations involving PPAR gamma agonists and the ketogenic diet in epilepsy rodent models.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Endocrinology & Metabolism
Shucai Yang, Zhongqin Gong, Zhimin Liu, Minghui Wei, Lingbin Xue, Alexander C. C. Vlantis, Yang Zhang, Jason YK. Chan, C. Andrew van Hasselt, Xianhai Zeng, Shuqi Qiu, Nelson Tang, Jing Du, Wei Wei, Michael C. F. Tong, George G. G. Chen
Summary: The levels of endogenous PPAR gamma ligands PGJ2 and 15(S)-HETE are significantly decreased in PTC. Inhibition of ER alpha or activation of ER beta can inhibit PTC by stimulating the production of endogenous PPAR gamma ligands to induce apoptosis in cancer cells.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Fisheries
Xiang-Yu Wu, Li Nie, Xin-Jiang Lu, Chen-Jie Fei, Jiong Chen
Summary: In this study, the role of PPAR gamma in immune regulation in teleost fish was investigated. Results showed that the expression of LcPPAR gamma changed during infection and DHA treatment, and was associated with the expression of immune-related genes.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Article
Pathology
Shinji Kaba, Yoshitaka Kawai, Yuki Tanigami, Hiroe Ohnishi, Tomoko Kita, Masayoshi Yoshimatsu, Koichi Omori, Yo Kishimoto
Summary: This study aimed to evaluate the effects of pioglitazone on macrophage phenotype and fibrosis following vocal fold injury. The results showed that pioglitazone reduced the expression of Ccl2, inhibited the accumulation of inflammatory macrophages, and improved tissue repair in a PPARy-dependent manner, resulting in decreased fibrosis.
AMERICAN JOURNAL OF PATHOLOGY
(2022)
Article
Microbiology
Yi-Hsin Lai, Tai-Chieh Wu, Bo-Yang Tsai, Yuan-Pin Hung, Hsiao-Ju Lin, Yau-Sheng Tsai, Wen-Chien Ko, Pei-Jane Tsai
Summary: PPAR-γ plays an important role in the pathogenesis of CDI by regulating colonic inflammation and integrity.
FRONTIERS IN MICROBIOLOGY
(2022)