Effects of the combination of Epimedii Folium and Ligustri Lucidi Fructus on apoptosis and autophagy in SOP rats and osteoblasts via PI3K/AKT/mTOR pathway

Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved..

BACKGROUND: This study aimed to investigate the effects of the combination of Epimedii Folium (EF) and Ligustri Lucidi Fructus (LLF) on regulating apoptosis and autophagy in senile osteoporosis (SOP) rats.

METHODS: Firstly, we identified the components in the decoction and drug-containing serum of EL (EF&LLF) by Ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS). Secondly, SOP rats were treated with EF, LLF, EL and caltrate to evaluate the advantages of EL. Finally, H2O2-, chloroquine-, and MHY1485-induced osteoblasts were treated with different doses of EL to reveal the molecular mechanism of EL. We detected bone microstructure, oxidative stress levels, ALP activity and the expressions of Bax, Bcl-2, caspase3, P53, Beclin-1, p-PI3K, PI3K, p-Akt, Akt, p-mTOR, mTOR, and LC3 in vivo and in vitro.

RESULTS: 36 compounds in EL decoction and 23 in EL-containing serum were identified, including flavonoids, iridoid terpenoids, phenylethanoid glycosides, polyols and triterpenoids. EL could inhibit apoptosis activity and increase ALP activity. In SOP rats and chloroquine-inhibited osteoblasts, EL could improve bone tissue microstructure and osteoblasts functions by upregulating Bcl-2, Beclin1, and LC3-II/LC3-I, while downregulating p53 in all treatment groups. In H2O2-induced osteoblasts, EL could upregulate the protein and mRNA expressions of Bcl-2 while downregulate LC3-II/LC3-I, p53 and Beclin1. Besides, EL was able to down-regulate PI3K/AKT/mTOR pathway which activated in SOP rats and MHY1485-induced osteoblasts.

CONCLUSIONS: These findings demonstrate that EL with bone protective effects on SOP rats by regulating autophagy and apoptosis via PI3K/Akt/mTOR signaling pathway, which might be an alternative medicine for the treatment of SOP.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:173

Enthalten in:

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie - 173(2024) vom: 25. März, Seite 116346

Sprache:

Englisch

Beteiligte Personen:

Li, Yuman [VerfasserIn]
Yu, Ping [VerfasserIn]
Gao, Yingying [VerfasserIn]
Ma, Zitong [VerfasserIn]
Wang, Han [VerfasserIn]
Long, Yuting [VerfasserIn]
Ma, Zaina [VerfasserIn]
Liu, Renhui [VerfasserIn]

Links:

Volltext

Themen:

886U3H6UFF
Autophagy / apoptosis
BBX060AN9V
Beclin-1
Chloroquine
Drugs, Chinese Herbal
EC 2.7.1.-
EC 2.7.1.1
EC 2.7.11.1
Epimedii Folium / Ligustri Lucidi Fructus
Epimedii flavone
Hydrogen Peroxide
Journal Article
MTOR protein, rat
Osteoblast
PI3K/Akt/mTOR
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
Proto-Oncogene Proteins c-bcl-2
Senile osteoporosis
TOR Serine-Threonine Kinases
Tumor Suppressor Protein p53
UPLC-Q-TOF-MS

Anmerkungen:

Date Completed 27.03.2024

Date Revised 27.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.biopha.2024.116346

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM36918193X