JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

Hydroxy-α-sanshool–loaded adipose-targeted mesoporous silica nanoparticles induce white adipose browning and reduce obesity by activating TRPV1

Author(s): zQing Zhang, Chengxun He, Juan Guo, Dandan Tang, Die Qian, Chuan Zheng, Chunjie Wu, Wei Peng
Affiliation(s): State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Innovative Institute of Chinese Medicine and Pharmacy/Academy for Interdiscipline, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, P.R. China; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109, USA; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, P.R. China; Sichuan Provincial Engineering Research Center of Innovative Re-development of Famous Classical Formulas, Tianfu TCM Innovation Harbour, Chengdu University of Traditional Chinese Medicine, Chengdu 611930, P.R. China
Corresponding email(s): zhengchuan@cdutcm.edu.cn, wuchunjie@cdutcm.edu.cn, pengwei@cdutcm.edu.cn
Key Words: Hydroxy-α-sanshool · Adipocyte targetability · Mesoporous silica nanoparticles · White adipose tissue brown‐ ing · Obesity

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zQing Zhang, Chengxun He, Juan Guo, Dandan Tang, Die Qian, Chuan Zheng, Chunjie Wu, Wei Peng. Hydroxy-α-sanshool–loaded adipose-targeted mesoporous silica nanoparticles induce white adipose browning and reduce obesity by activating TRPV1[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/bdm.2400248

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author="zQing Zhang, Chengxun He, Juan Guo, Dandan Tang, Die Qian, Chuan Zheng, Chunjie Wu, Wei Peng",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/bdm.2400248"
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A1 - Chunjie Wu
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doi="https://doi.org/10.1631/bdm.2400248"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Obesity has become a global threat to health, and however the available drugs for treating obesity are limited. We investi‐ gated the anti-obesity effect of hydroxy-α-sanshool (HAS), an amide derived from the fruit of Zanthoxylum bungeanum, which promotes the management of obesity by triggering the browning of white adipose tissue (WAT) targeting the membrane re‐ ceptor of TRPV1. However, HAS easily undergoes configuration transformation and oxidative degradation. Mesoporous silica nanoparticles (MSNs) are widely used in drug delivery systems because of their large specific surface area and pore volume. Furthermore, the short peptide CKGGRAKDC or adipose-targeting sequence (ATS) binds specifically to prohibitin on the surface of WAT cells and can be used to modify MSNs to enhance adipocyte targetability. Therefore, HAS-loaded adipose-targeted MSNs (MSN-ATS) were developed to enhance the adipocyte targetability, safety and efficacy of HAS, and tested on mature 3T3-L1 cells and obese mouse models. MSNs-ATS showed higher specificity for adipocyte targetability without obvious toxicity. HAS-loaded MSNs-ATS showed anti-obesity effects superior to those of HAS alone. In conclu‐ sion, we successfully developed adipocyte-targeted, HAS-loaded MSNs with good safety and anti-obesity effects.

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