Prinsepiae Nux Extract Activates NRF2 Activity and Protects UVB-Induced Damage in Keratinocyte

Shih Han Wang; Yi Siao Chen; Kuei Hung Lai; Chung Kuang Lu; Hsun Shuo Chang; Ho Cheng Wu; Feng Lin Yen; Lo Yun Chen; Jin Ching Lee; Chia Hung Yen

doi:10.3390/antiox11091755

Prinsepiae Nux Extract Activates NRF2 Activity and Protects UVB-Induced Damage in Keratinocyte

Shih Han Wang, Yi Siao Chen, Kuei Hung Lai, Chung Kuang Lu, Hsun Shuo Chang, Ho Cheng Wu, Feng Lin Yen, Lo Yun Chen, Jin Ching Lee, Chia Hung Yen

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Ultraviolet B (UVB) is one of the most important environmental factors that cause extrinsic aging through increasing intracellular reactive oxygen species (ROS) production in the skin. Due to its protective roles against oxidative stress, nuclear factor erythroid-2-related factor (NRF2) has been traditionally considered as a target for skin aging prevention. Here, we identified the extract of Prinsepiae Nux, a top-grade drug listed in Shen Nong Ben Cao Jing, as a potent NRF2 activator by high-throughput screening. A bioassay-guided fractionation experiment revealed that NRF2-activating components were concentrated in the 90% methanol (MP) fraction. MP fraction significantly increased the expression of NRF2 and HO-1 protein and upregulated HO-1 and NQO1 mRNA expression in HaCaT cells. Moreover, MP fraction pre-treatment dramatically reversed UVB-induced depletion of NRF2 and HO-1, accumulation of intracellular ROS, NF-κB activation, and the upregulation of pro-inflammatory genes. Finally, the qualitative analysis using UPLC-tandem mass spectroscopy revealed the most abundant ion peak in MP fraction was identified as α-linolenic acid, which was further proved to activate NRF2 signaling. Altogether, the molecular evidence suggested that MP fraction has the potential to be an excellent source for the discovery of natural medicine to treat/prevent UVB-induced skin damage.

Original language	English
Article number	1755
Journal	Antioxidants
Volume	11
Issue number	9
DOIs	https://doi.org/10.3390/antiox11091755
Publication status	Published - Sept 2022

Keywords

antioxidant
natural product
NRF2
ROS
Shen Nong Ben Cao Jing
UVB irradiation

ASJC Scopus subject areas

Food Science
Physiology
Biochemistry
Molecular Biology
Clinical Biochemistry
Cell Biology

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10.3390/antiox11091755

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@article{fa9a361ab6e9463b85048cf4c8764a8c,

title = "Prinsepiae Nux Extract Activates NRF2 Activity and Protects UVB-Induced Damage in Keratinocyte",

abstract = "Ultraviolet B (UVB) is one of the most important environmental factors that cause extrinsic aging through increasing intracellular reactive oxygen species (ROS) production in the skin. Due to its protective roles against oxidative stress, nuclear factor erythroid-2-related factor (NRF2) has been traditionally considered as a target for skin aging prevention. Here, we identified the extract of Prinsepiae Nux, a top-grade drug listed in Shen Nong Ben Cao Jing, as a potent NRF2 activator by high-throughput screening. A bioassay-guided fractionation experiment revealed that NRF2-activating components were concentrated in the 90% methanol (MP) fraction. MP fraction significantly increased the expression of NRF2 and HO-1 protein and upregulated HO-1 and NQO1 mRNA expression in HaCaT cells. Moreover, MP fraction pre-treatment dramatically reversed UVB-induced depletion of NRF2 and HO-1, accumulation of intracellular ROS, NF-κB activation, and the upregulation of pro-inflammatory genes. Finally, the qualitative analysis using UPLC-tandem mass spectroscopy revealed the most abundant ion peak in MP fraction was identified as α-linolenic acid, which was further proved to activate NRF2 signaling. Altogether, the molecular evidence suggested that MP fraction has the potential to be an excellent source for the discovery of natural medicine to treat/prevent UVB-induced skin damage.",

keywords = "antioxidant, natural product, NRF2, ROS, Shen Nong Ben Cao Jing, UVB irradiation",

author = "Wang, {Shih Han} and Chen, {Yi Siao} and Lai, {Kuei Hung} and Lu, {Chung Kuang} and Chang, {Hsun Shuo} and Wu, {Ho Cheng} and Yen, {Feng Lin} and Chen, {Lo Yun} and Lee, {Jin Ching} and Yen, {Chia Hung}",

note = "Funding Information: We thank the Drug Development and Value Creation Research Center of Kaohsiung Medical University for providing research instruments and workspace, and we thank the staff from the National Natural Product Libraries and High-Throughput Screening Core Facility (NPS core lab) at Kaohsiung Medical University for technical assistance. This research was funded by the Ministry of Science and Technology, Taiwan (grant numbers: MOST 110-2740-B-037-001 and MOST 109-2314-B-037-047-MY3) and the NSYSU–KMU Joint Research Project (grant number: NSYSYKMU 111-I06). Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = sep,

doi = "10.3390/antiox11091755",

language = "English",

volume = "11",

journal = "Antioxidants",

issn = "2076-3921",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "9",

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T1 - Prinsepiae Nux Extract Activates NRF2 Activity and Protects UVB-Induced Damage in Keratinocyte

AU - Wang, Shih Han

AU - Chen, Yi Siao

AU - Lai, Kuei Hung

AU - Lu, Chung Kuang

AU - Chang, Hsun Shuo

AU - Wu, Ho Cheng

AU - Yen, Feng Lin

AU - Chen, Lo Yun

AU - Lee, Jin Ching

AU - Yen, Chia Hung

N1 - Funding Information: We thank the Drug Development and Value Creation Research Center of Kaohsiung Medical University for providing research instruments and workspace, and we thank the staff from the National Natural Product Libraries and High-Throughput Screening Core Facility (NPS core lab) at Kaohsiung Medical University for technical assistance. This research was funded by the Ministry of Science and Technology, Taiwan (grant numbers: MOST 110-2740-B-037-001 and MOST 109-2314-B-037-047-MY3) and the NSYSU–KMU Joint Research Project (grant number: NSYSYKMU 111-I06). Publisher Copyright: © 2022 by the authors.

PY - 2022/9

Y1 - 2022/9

N2 - Ultraviolet B (UVB) is one of the most important environmental factors that cause extrinsic aging through increasing intracellular reactive oxygen species (ROS) production in the skin. Due to its protective roles against oxidative stress, nuclear factor erythroid-2-related factor (NRF2) has been traditionally considered as a target for skin aging prevention. Here, we identified the extract of Prinsepiae Nux, a top-grade drug listed in Shen Nong Ben Cao Jing, as a potent NRF2 activator by high-throughput screening. A bioassay-guided fractionation experiment revealed that NRF2-activating components were concentrated in the 90% methanol (MP) fraction. MP fraction significantly increased the expression of NRF2 and HO-1 protein and upregulated HO-1 and NQO1 mRNA expression in HaCaT cells. Moreover, MP fraction pre-treatment dramatically reversed UVB-induced depletion of NRF2 and HO-1, accumulation of intracellular ROS, NF-κB activation, and the upregulation of pro-inflammatory genes. Finally, the qualitative analysis using UPLC-tandem mass spectroscopy revealed the most abundant ion peak in MP fraction was identified as α-linolenic acid, which was further proved to activate NRF2 signaling. Altogether, the molecular evidence suggested that MP fraction has the potential to be an excellent source for the discovery of natural medicine to treat/prevent UVB-induced skin damage.

AB - Ultraviolet B (UVB) is one of the most important environmental factors that cause extrinsic aging through increasing intracellular reactive oxygen species (ROS) production in the skin. Due to its protective roles against oxidative stress, nuclear factor erythroid-2-related factor (NRF2) has been traditionally considered as a target for skin aging prevention. Here, we identified the extract of Prinsepiae Nux, a top-grade drug listed in Shen Nong Ben Cao Jing, as a potent NRF2 activator by high-throughput screening. A bioassay-guided fractionation experiment revealed that NRF2-activating components were concentrated in the 90% methanol (MP) fraction. MP fraction significantly increased the expression of NRF2 and HO-1 protein and upregulated HO-1 and NQO1 mRNA expression in HaCaT cells. Moreover, MP fraction pre-treatment dramatically reversed UVB-induced depletion of NRF2 and HO-1, accumulation of intracellular ROS, NF-κB activation, and the upregulation of pro-inflammatory genes. Finally, the qualitative analysis using UPLC-tandem mass spectroscopy revealed the most abundant ion peak in MP fraction was identified as α-linolenic acid, which was further proved to activate NRF2 signaling. Altogether, the molecular evidence suggested that MP fraction has the potential to be an excellent source for the discovery of natural medicine to treat/prevent UVB-induced skin damage.

KW - antioxidant

KW - natural product

KW - NRF2

KW - ROS

KW - Shen Nong Ben Cao Jing

KW - UVB irradiation

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U2 - 10.3390/antiox11091755

DO - 10.3390/antiox11091755

M3 - Article

AN - SCOPUS:85138561847

SN - 2076-3921

VL - 11

JO - Antioxidants

JF - Antioxidants

IS - 9

M1 - 1755

ER -

Prinsepiae Nux Extract Activates NRF2 Activity and Protects UVB-Induced Damage in Keratinocyte

Abstract

Keywords

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