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Anti-insulin resistance effect of constituents from Senna siamea on zebrafish model, its molecular docking, and structure–activity relationships

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Abstract

Senna siamea has been used as an antidiabetic drug since antiquity. With regard to traditional Thai medicine, the use of S. siamea was described for diabetes therapy. To understand the molecular mechanism regarding insulin resistance. Pure compounds were isolated from wood extract. We studied their biological activities on insulin-resistance using an in vivo zebrafish model. We also performed an in silico study; molecular docking, and in vitro study by taking advantage of the enzyme inhibitory activities of α-glucosidase, PTP1B, and DPP-IV. Based on the preliminary investigation that ethyl acetate and ethanol extracts have potent effects against insulin resistance on zebrafish larvae, five compounds were isolated from two fractions following: resveratrol, piceatannol, dihydropiceatannol, chrysophanol, and emodin. All of the isolated compounds had anti-insulin resistance effects on zebrafish larvae. Resveratrol, piceatannol, and dihydropiceatannol also demonstrated inhibitory effects against α-glucosidase. Chrysophanol and emodin inhibited PTP1B activity, while resveratrol showed a DPP-IV inhibition effect via the molecular docking. The results of enzyme assay were similar. In conclusions, S. siamea components demonstrated effects against insulin resistance. The chemical structure displayed identical biological activity to that of the compounds. Therefore, S. siamea wood extract and their components are potential therapeutic options in the treatment of diabetes.

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Abbreviations

1H NMR:

Proton nuclear magnetic resonance

DPP-IV:

Dipeptidyl peptidase IV

EDTA:

Ethylenediaminetetraacetic acid

GLP-1:

Glucagon-like peptide 1

dpf:

Days post-fertilization

GPPN:

Gly-Pro-ρ-nitroanilinde

hpf:

Hours post-fertilization

IC50 :

The half maximal inhibitory concentration

PI:

Pancreatic islet

PNPG:

ρ-Nitrophenyl-α-d-glucopyranoside

PNPP:

ρ-Nitrophenyl phosphate

PTP1B:

Protein tyrosine phosphatase 1B

ptpn6:

Protein tyrosine phosphatase nonreceptor type 6

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Acknowledgements

This research was supported by the MSIT (Ministry of Science and ICT), Korea, under the ICT Consilience Creative program (IITP-2020-2015-0-00742) supervised by the IITP (Institute for Information and communications Technology Planning and Evaluation). The phytochemical study was financially supported by the Plant Genetic Conservation Project under The Royal Initiative of Her Royal Highness Princess Maha Chakri Sirindhorn (RSPG project).

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Authors and Affiliations

  1. Laboratory of Natural Product Pharmacology and Hearing Loss, Graduate School of Biotechnology, Department of Oriental Medicine Biotechnology, College of Life Sciences, Kyung Hee University, 1732, Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 17104, Republic of Korea

    Wanlapa Nuankaew, Ji Heon Shim, Na Woo Kim, Tamanna Yasmin, Seo Yule Jeong, Youn Hee Nam, Bin Na Hong & Tong Ho Kang

  2. Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla, Thailand

    Armad Heemman, Chatchai Wattanapiromsakul & Sukanya Dej-adisai

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  1. Wanlapa Nuankaew
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Correspondence to Tong Ho Kang.

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Nuankaew, W., Heemman, A., Wattanapiromsakul, C. et al. Anti-insulin resistance effect of constituents from Senna siamea on zebrafish model, its molecular docking, and structure–activity relationships. J Nat Med 75, 520–531 (2021). https://doi.org/10.1007/s11418-021-01490-5

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