Pimarane Diterpenoids from the Seeds of Caesalpinia minax as PTP1B Inhibitors and Insulin Sensitizers

Xu, Yunshao; Feng, Zheling; Zhang, Tian; Lv, Peng; Cao, Jun; Li, Dan; Peng, Cheng; Lin, Ligen

doi:10.3390/molecules25204674

Open AccessArticle

Pimarane Diterpenoids from the Seeds of Caesalpinia minax as PTP1B Inhibitors and Insulin Sensitizers

by

Yunshao Xu

^1,†,

Zheling Feng

^1,†,

Tian Zhang

¹,

Peng Lv

¹,

Jun Cao

¹,

Dan Li

²,

Cheng Peng

² and

Ligen Lin

^1,2,*

¹

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, China

²

State Key Laboratory of Southwestern Characteristic Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Molecules 2020, 25(20), 4674; https://doi.org/10.3390/molecules25204674

Submission received: 15 September 2020 / Revised: 6 October 2020 / Accepted: 12 October 2020 / Published: 13 October 2020

(This article belongs to the Special Issue Advances on Natural Compounds Research: Chemistry, Biology and Biotechnology)

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Abstract

Protein-tyrosine phosphatase 1B (PTP1B) has been considered as a promising target for treating insulin resistance. In searching for naturally occurring PTB1B antagonists, two new pimarane diterpenoids, named 2α-hydroxy-7-oxo-pimara-8(9),15-diene (1) and 19-hydroxy-2α-acetoxy-7-oxo-pimara-8(9),15-diene (2), were isolated from the seeds of Caesalpinia minax. Their structures were determined by extensive analysis of NMR and HR-ESIMS data, and their absolute configurations were determined by electronic circular dichroism (ECD) spectra. Compound 1 was disclosed as a competitive inhibitor of PTP1B with an IC₅₀ (the half-maximal inhibitory concentration) value of 19.44 ± 2.39 µM and a Ki (inhibition constant) value of 13.69 ± 2.72 μM. Moreover, compound 1 dose-dependently promoted insulin-stimulated glucose uptake in C2C12 myotubes through activating insulin signaling pathway. Compound 1 might be further developed as an insulin sensitizer.

Keywords: pimarane diterpenoids; Caesalpinia minax; PTP1B; glucose uptake; C2C12 myotubes

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MDPI and ACS Style

Xu, Y.; Feng, Z.; Zhang, T.; Lv, P.; Cao, J.; Li, D.; Peng, C.; Lin, L. Pimarane Diterpenoids from the Seeds of Caesalpinia minax as PTP1B Inhibitors and Insulin Sensitizers. Molecules 2020, 25, 4674. https://doi.org/10.3390/molecules25204674

AMA Style

Xu Y, Feng Z, Zhang T, Lv P, Cao J, Li D, Peng C, Lin L. Pimarane Diterpenoids from the Seeds of Caesalpinia minax as PTP1B Inhibitors and Insulin Sensitizers. Molecules. 2020; 25(20):4674. https://doi.org/10.3390/molecules25204674

Chicago/Turabian Style

Xu, Yunshao, Zheling Feng, Tian Zhang, Peng Lv, Jun Cao, Dan Li, Cheng Peng, and Ligen Lin. 2020. "Pimarane Diterpenoids from the Seeds of Caesalpinia minax as PTP1B Inhibitors and Insulin Sensitizers" Molecules 25, no. 20: 4674. https://doi.org/10.3390/molecules25204674

APA Style

Xu, Y., Feng, Z., Zhang, T., Lv, P., Cao, J., Li, D., Peng, C., & Lin, L. (2020). Pimarane Diterpenoids from the Seeds of Caesalpinia minax as PTP1B Inhibitors and Insulin Sensitizers. Molecules, 25(20), 4674. https://doi.org/10.3390/molecules25204674

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Pimarane Diterpenoids from the Seeds of Caesalpinia minax as PTP1B Inhibitors and Insulin Sensitizers

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