PMID- 34552493
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210925
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - A Novel 5-HT(1B) Receptor Agonist of Herbal Compounds and One of the Therapeutic 
      Uses for Alzheimer's Disease.
PG  - 735876
LID - 10.3389/fphar.2021.735876 [doi]
LID - 735876
AB  - The serotonin receptor 5-HT(1B) is widely expressed in the central nervous system 
      and has been considered a drug target in a variety of cognitive and psychiatric 
      disorders. The anti-inflammatory effects of 5-HT(1B) agonists may present a 
      promising approach for Alzheimer's disease (AD) treatment. Herbal antidepressants 
      used in the treatment of AD have shown functional overlap between the active 
      compounds and 5-HT(1B) receptor stimulation. Therefore, compounds in these 
      medicinal plants that target and stimulate 5-HT(1B) deserve careful study. 
      Molecular docking, drug affinity responsive target stability, cellular thermal 
      shift assay, fluorescence resonance energy transfer (FRET), and extracellular 
      regulated protein kinases (ERK) 1/2 phosphorylation tests were used to identify 
      emodin-8-O-beta-d-glucopyranoside (EG), a compound from Chinese medicinal plants 
      with cognitive deficit attenuating and antidepressant effects, as an agonist of 
      5-HT(1B). EG selectively targeted 5-HT(1B) and activated the 5-HT(1B)-induced 
      signaling pathway. The activated 5-HT(1B) pathway suppressed tumor necrosis 
      factor (TNF)-alpha levels, thereby protecting neural cells against beta-amyloid 
      (Abeta)-induced death. Moreover, the agonist activity of EG towards 5-HT(1B) 
      receptor, in FRET and ERK1/2 phosphorylation, was antagonized by SB 224289, a 
      5-HT(1B) antagonist. In addition, EG relieved AD symptoms in transgenic worm 
      models. These results suggested that 5-HT(1B) receptor activation by EG 
      positively affected Abeta-related inflammatory process regulation and neural death 
      resistance, which were reversed by antagonist SB 224289. The active compounds 
      such as EG might act as potential therapeutic agents through targeting and 
      stimulating 5-HT(1B) receptor for AD and other serotonin-related disorders. This 
      study describes methods for identification of 5-HT(1B) agonists from herbal 
      compounds and for evaluating agonists with biological functions, providing 
      preliminary information on medicinal herbal pharmacology.
CI  - Copyright (c) 2021 Yang, Zhang, Yu, Ma, Li, Wang, Hu, Zou, Liu, Liu, An, Xiang, 
      Guo, Hao and Xu.
FAU - Yang, Yang
AU  - Yang Y
AD  - Center for Pharmaceutical Sciences and Engineering, Faculty of Life Science and 
      Technology, Kunming University of Science and Technology, Kunming, China.
FAU - Zhang, Lijing
AU  - Zhang L
AD  - Center for Pharmaceutical Sciences and Engineering, Faculty of Life Science and 
      Technology, Kunming University of Science and Technology, Kunming, China.
FAU - Yu, Jiaojiao
AU  - Yu J
AD  - Center for Pharmaceutical Sciences and Engineering, Faculty of Life Science and 
      Technology, Kunming University of Science and Technology, Kunming, China.
FAU - Ma, Zhaobin
AU  - Ma Z
AD  - Center for Pharmaceutical Sciences and Engineering, Faculty of Life Science and 
      Technology, Kunming University of Science and Technology, Kunming, China.
FAU - Li, Moxiang
AU  - Li M
AD  - Center for Pharmaceutical Sciences and Engineering, Faculty of Life Science and 
      Technology, Kunming University of Science and Technology, Kunming, China.
FAU - Wang, Jin
AU  - Wang J
AD  - Center for Pharmaceutical Sciences and Engineering, Faculty of Life Science and 
      Technology, Kunming University of Science and Technology, Kunming, China.
FAU - Hu, Pengcheng
AU  - Hu P
AD  - Center for Pharmaceutical Sciences and Engineering, Faculty of Life Science and 
      Technology, Kunming University of Science and Technology, Kunming, China.
FAU - Zou, Jia
AU  - Zou J
AD  - Center for Pharmaceutical Sciences and Engineering, Faculty of Life Science and 
      Technology, Kunming University of Science and Technology, Kunming, China.
FAU - Liu, Xueying
AU  - Liu X
AD  - Center for Pharmaceutical Sciences and Engineering, Faculty of Life Science and 
      Technology, Kunming University of Science and Technology, Kunming, China.
FAU - Liu, Ying
AU  - Liu Y
AD  - Center for Pharmaceutical Sciences and Engineering, Faculty of Life Science and 
      Technology, Kunming University of Science and Technology, Kunming, China.
FAU - An, Su
AU  - An S
AD  - Center for Pharmaceutical Sciences and Engineering, Faculty of Life Science and 
      Technology, Kunming University of Science and Technology, Kunming, China.
FAU - Xiang, Cheng
AU  - Xiang C
AD  - Center for Pharmaceutical Sciences and Engineering, Faculty of Life Science and 
      Technology, Kunming University of Science and Technology, Kunming, China.
FAU - Guo, Xiaoxi
AU  - Guo X
AD  - Center for Pharmaceutical Sciences and Engineering, Faculty of Life Science and 
      Technology, Kunming University of Science and Technology, Kunming, China.
FAU - Hao, Qian
AU  - Hao Q
AD  - Center for Pharmaceutical Sciences and Engineering, Faculty of Life Science and 
      Technology, Kunming University of Science and Technology, Kunming, China.
FAU - Xu, Tian-Rui
AU  - Xu TR
AD  - Center for Pharmaceutical Sciences and Engineering, Faculty of Life Science and 
      Technology, Kunming University of Science and Technology, Kunming, China.
LA  - eng
PT  - Journal Article
DEP - 20210906
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8450432
OTO - NOTNLM
OT  - 5-HT1B receptor
OT  - alzheimer's disease
OT  - drug affinity responsive target stability
OT  - emodin-8-O-beta-d-glucopyranoside
OT  - fluorescence resonance energy transfer
OT  - molecular docking
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/09/24 06:00
MHDA- 2021/09/24 06:01
PMCR- 2021/09/06
CRDT- 2021/09/23 06:48
PHST- 2021/07/18 00:00 [received]
PHST- 2021/08/23 00:00 [accepted]
PHST- 2021/09/23 06:48 [entrez]
PHST- 2021/09/24 06:00 [pubmed]
PHST- 2021/09/24 06:01 [medline]
PHST- 2021/09/06 00:00 [pmc-release]
AID - 735876 [pii]
AID - 10.3389/fphar.2021.735876 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Sep 6;12:735876. doi: 10.3389/fphar.2021.735876. 
      eCollection 2021.