Lophatherum gracile Brongn. attenuates neutrophilic inflammation through inhibition of JNK and calcium

Kuei-Hung Lai; Po-Jen Chen; Chih-Chuan Chen; Sien-Hung Yang; Mohamed El-Shazly; Yu-Chia Chang; Yi-Hsuan Wu; Yi-Hsiu Wu; Yi-Hsuan Wang; Hsi-Lung Hsieh; Tsong-Long Hwang

doi:10.1016/j.jep.2020.113224

Lophatherum gracile Brongn. attenuates neutrophilic inflammation through inhibition of JNK and calcium

J Ethnopharmacol. 2021 Jan 10:264:113224. doi: 10.1016/j.jep.2020.113224. Epub 2020 Aug 12.

Authors

Kuei-Hung Lai¹, Po-Jen Chen², Chih-Chuan Chen³, Sien-Hung Yang⁴, Mohamed El-Shazly⁵, Yu-Chia Chang⁶, Yi-Hsuan Wu⁷, Yi-Hsiu Wu⁸, Yi-Hsuan Wang⁹, Hsi-Lung Hsieh¹⁰, Tsong-Long Hwang¹¹

Affiliations

¹ Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, 33303, Taiwan; Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei, 11031, Taiwan. Electronic address: mos19880822@gmail.com.
² Department of Cosmetic Science, Providence University, Taichung, 43301, Taiwan. Electronic address: litlep@hotmail.com.
³ Graduate Institute of Natural Products, School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, 33302, Taiwan. Electronic address: pariede@gmail.com.
⁴ Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, 33305, Taiwan; School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, 33302, Taiwan. Electronic address: dryang@mail.cgu.edu.tw.
⁵ Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, Ain-Shams University, Organization of African Unity Street, Abassia, Cairo, 11566, Egypt; Department of Pharmaceutical Biology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, 11432, Egypt. Electronic address: mohamed.elshazly@pharma.asu.edu.eg.
⁶ Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, 33303, Taiwan. Electronic address: ycchang03@mail.cgust.edu.tw.
⁷ Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, 33303, Taiwan. Electronic address: yhwu03@mail.cgust.edu.tw.
⁸ Graduate Institute of Natural Products, School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, 33302, Taiwan. Electronic address: modemtw@gmail.com.
⁹ Graduate Institute of Natural Products, School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, 33302, Taiwan. Electronic address: e0919133641@gmail.com.
¹⁰ Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, 33303, Taiwan; Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Taoyuan, 33303, Taiwan; Department of Neurology, Chang Gung Memorial Hospital, Taoyuan, 33305, Taiwan. Electronic address: hlhsieh@mail.cgust.edu.tw.
¹¹ Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, 33303, Taiwan; Graduate Institute of Natural Products, School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, 33302, Taiwan; Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, 33303, Taiwan; Department of Anaesthesiology, Chang Gung Memorial Hospital, Taoyuan, 33305, Taiwan; Department of Chemical Engineering, Ming Chi University of Technology, New Taipei City, 24301, Taiwan. Electronic address: htl@mail.cgu.edu.tw.

PMID: 32800928
DOI: 10.1016/j.jep.2020.113224

Abstract

Ethnopharmacological relevance: Lophatherum gracile Brongn. (L. gracile) has been long used in traditional herbal medicine to clinically clear heat, disinhibit dampness, and treat inflammation. However, the effect of L. gracile on the activation of human neutrophils remains unclear.

Aim of the study: The aim of current study is to investigate the anti-inflammatory properties of L. gracile extract (LGE) in N-formyl-methionyl-leucyl-phenylalanine (fMLF)-induced activation of human neutrophils.

Materials and methods: Superoxide anion generation and elastase release were estimated by spectrophotometry. A series of signaling pathways including mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt), as well as calcium mobilization were studied by Western blot analysis and spectrofluorometry.

Results: Our experimental results indicated that the nontoxic dosage of LGE does-dependently inhibited the fMLF-induced superoxide anion (O₂^•-) generation, elastase release, CD11b expression, adhesion, and chemotactic migration in human neutrophils. LGE selectively inhibited the fMLF-induced phosphorylation of JNK but not p38, ERK, or Akt in human neutrophils. LGE also decreased the intracellular Ca²⁺ levels ([Ca²⁺]_i) in fMLF-activated human neutrophils. However, a specific JNK inhibitor inhibited the fMLF-induced O₂^•- generation and CD11b expression, but it had no effect on [Ca²⁺]_i in human neutrophils.

Conclusions: LGE exhibited anti-inflammatory activities in fMLF-activated human neutrophils. The pharmacological mechanisms of LGE-repressed neutrophilic inflammation were through two independent pathways, JNK signaling and calcium mobilization. Our results suggested that LGE holds the potential to be developed as an anti-inflammatory botanical medicine.

Keywords: Calcium mobilization; JNK; Lophatherum gracile Brongn.; Neutrophilic inflammation.

MeSH terms

Adult
Anti-Inflammatory Agents / isolation & purification
Anti-Inflammatory Agents / pharmacology*
Calcium Signaling / drug effects*
Calcium Signaling / physiology
Dose-Response Relationship, Drug
Drugs, Chinese Herbal / isolation & purification
Drugs, Chinese Herbal / pharmacology*
Female
Humans
MAP Kinase Signaling System / drug effects*
MAP Kinase Signaling System / physiology
Male
Neutrophils / drug effects*
Neutrophils / metabolism
Neutrophils / pathology
Plants, Medicinal*
Young Adult

Substances

Anti-Inflammatory Agents
Drugs, Chinese Herbal