PMID- 33781874
OWN - NLM
STAT- MEDLINE
DCOM- 20220120
LR  - 20220120
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 168
DP  - 2021 Jun
TI  - Regulation of ferroptosis by bioactive phytochemicals: Implications for medical 
      nutritional therapy.
PG  - 105580
LID - S1043-6618(21)00164-X [pii]
LID - 10.1016/j.phrs.2021.105580 [doi]
AB  - Ferroptosis is an iron- and lipotoxicity-dependent regulated cell death that has 
      been implicated in various diseases, such as cancer, neurodegeneration and 
      stroke. The biosynthesis of phospholipids, coenzyme Q(10), and glutathione, and 
      the metabolism of iron, amino acids and polyunsaturated fatty acid, are tightly 
      associated with cellular sensitivity to ferroptosis. Up to now, only limited 
      drugs targeting ferroptosis have been documented and exploring novel effective 
      ferroptosis-modulating compound is needed. Natural bioactive products are 
      conventional resources for drug discovery, and some of them have been clinically 
      used against cancers and neurodegenerative diseases as dietary supplements or 
      pharmaceutic agents. Notably, increasing evidence demonstrates that natural 
      compounds, such as saponins, flavonoids and isothiocyanates, can either induce or 
      inhibit ferroptosis, further expanding their therapeutic potentials. In this 
      review, we highlight current advances of the emerging molecular mechanisms and 
      disease relevance of ferroptosis. We also systematically summarize the regulatory 
      effects of natural phytochemicals on ferroptosis, and clearly indicate that 
      saponins, terpenoids and alkaloids induce ROS- and ferritinophagy-dependent 
      ferroptosis, whereas flavonoids and polyphenols modulate iron metabolism and 
      nuclear factor erythroid 2-related factor 2 (NRF2) signaling to inhibit 
      ferroptosis. Finally, we explore their clinical applications in 
      ferroptosis-related diseases, which may facilitate the development of their 
      dietary usages as nutraceuticals.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Zheng, Kai
AU  - Zheng K
AD  - School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, 
      Shenzhen 518060, PR China. Electronic address: zhengk@szu.edu.cn.
FAU - Dong, Yun
AU  - Dong Y
AD  - School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, 
      Shenzhen 518060, PR China.
FAU - Yang, Rong
AU  - Yang R
AD  - School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, 
      Shenzhen 518060, PR China.
FAU - Liang, Youfang
AU  - Liang Y
AD  - School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, 
      Shenzhen 518060, PR China.
FAU - Wu, Haiqiang
AU  - Wu H
AD  - School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, 
      Shenzhen 518060, PR China.
FAU - He, Zhendan
AU  - He Z
AD  - School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, 
      Shenzhen 518060, PR China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20210327
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Phospholipids)
RN  - 0 (Phytochemicals)
RN  - 0 (Plant Extracts)
RN  - E1UOL152H7 (Iron)
RN  - S5UOB36OCZ (Mevalonic Acid)
SB  - IM
MH  - Dietary Supplements
MH  - Ferroptosis/*drug effects
MH  - Humans
MH  - Iron/metabolism
MH  - Mevalonic Acid/metabolism
MH  - Neoplasms/drug therapy
MH  - Oxidative Stress/drug effects
MH  - Phospholipids/metabolism
MH  - Phytochemicals/*pharmacology
MH  - Plant Extracts/pharmacology
OTO - NOTNLM
OT  - Cancer therapy
OT  - Ferroptosis
OT  - Iron metabolism
OT  - Lipid peroxidation
OT  - NRF2
OT  - Natural phytochemicals
OT  - Reactive oxygen species
EDAT- 2021/03/31 06:00
MHDA- 2022/01/21 06:00
CRDT- 2021/03/30 06:24
PHST- 2021/01/25 00:00 [received]
PHST- 2021/03/15 00:00 [revised]
PHST- 2021/03/23 00:00 [accepted]
PHST- 2021/03/31 06:00 [pubmed]
PHST- 2022/01/21 06:00 [medline]
PHST- 2021/03/30 06:24 [entrez]
AID - S1043-6618(21)00164-X [pii]
AID - 10.1016/j.phrs.2021.105580 [doi]
PST - ppublish
SO  - Pharmacol Res. 2021 Jun;168:105580. doi: 10.1016/j.phrs.2021.105580. Epub 2021 
      Mar 27.