PMID- 37914430
OWN - NLM
STAT- MEDLINE
DCOM- 20240118
LR  - 20240325
IS  - 1747-0285 (Electronic)
IS  - 1747-0277 (Linking)
VI  - 103
IP  - 1
DP  - 2024 Jan
TI  - Kaempferol exerts antioxidant effects in age-related diminished ovarian reserve 
      by regulating the HSP90/NRF2 pathway.
PG  - e14385
LID - 10.1111/cbdd.14385 [doi]
AB  - Kaempferol is the active ingredient of Er-Xian decoction (EXD), a traditional 
      Chinese medicine formula used clinically to treat ovarian dysfunction, but the 
      mechanism of kaempferol relieving age-related diminished ovarian reserve (AR-DOR) 
      is still unclear. In this study, 36 volunteers and 78 DOR patients (37 patients 
      with EXD treatment) were enrolled in the clinical research. Meanwhile, 
      32-week-old female mice were used to establish the AR-DOR model, and these model 
      mice were intragastrically administered with 100 mg/kg kaempferol in the presence 
      or absence of 200 mg/kg geranylgeranylacetone (GGA) or 1 mg/kg geldanamycin 
      (GDA). The effects of kaempferol on serum hormone levels and oxidative 
      stress-related indexes were detected by enzyme-linked immunosorbent assay. Antral 
      follicle count (AFC) was determined by hematoxylin-eosin staining. The protein 
      levels of HSP90 and nuclear factor erythroid 2-related factor 2 (NRF2) were 
      assayed by Western blot. This study displayed that the serum anti-Mullerian 
      hormone (AMH) level in DOR patients with EXD treatment was higher than that in 
      DOR patients without EXD treatment. Kaempferol treatment reversed the low levels 
      of AMH, estradiol (E2), AFC, superoxide dismutase (SOD), and catalase (CAT), as 
      well as the high levels of follicle-stimulating hormone (FSH), reactive oxygen 
      species (ROS), and malonaldehyde (MDA). The results showed that HSP90 was 
      predicted to have high affinity with kaempferol, and its expression was inhibited 
      by kaempferol, while the expression of NRF2, the target of HSP90, was 
      up-regulated by kaempferol. However, the above effects of kaempferol were 
      reversed by GGA. On the contrary, GDA enhanced the therapeutic effects of 
      kaempferol on AR-DOR mice. Moreover, the treatment of kaempferol resulted in a 
      reduction in the phosphorylation level of heat shock factor 1 (HSF1), the 
      transcription factor associated with HSP90, and an increase in the 
      phosphorylation level of Src, a client protein of HSP90. In summary, kaempferol 
      exerts an antioxidant effect on AR-DOR by inhibiting HSP90 expression to 
      up-regulate NRF2 expression. This study provides a theoretical basis for the 
      clinical application of kaempferol in AR-DOR.
CI  - (c) 2023 John Wiley & Sons A/S.
FAU - Hua, Zhoujia
AU  - Hua Z
AD  - Department of Reproduction, Zhejiang Hospital of Integrated Traditional Chinese 
      and Western Medicine, Hangzhou, China.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Department of Reproduction, Zhejiang Hospital of Integrated Traditional Chinese 
      and Western Medicine, Hangzhou, China.
FAU - Han, Lin
AU  - Han L
AD  - Department of Reproduction, Zhejiang Hospital of Integrated Traditional Chinese 
      and Western Medicine, Hangzhou, China.
FAU - Zhang, Yuwei
AU  - Zhang Y
AD  - Second Clinical Medical School, Zhejiang Chinese Medical University, Hangzhou, 
      China.
FAU - Jiang, Xuejuan
AU  - Jiang X
AD  - Department of Reproduction, Zhejiang Hospital of Integrated Traditional Chinese 
      and Western Medicine, Hangzhou, China.
FAU - Ding, Caifei
AU  - Ding C
AD  - Department of Reproduction, Zhejiang Hospital of Integrated Traditional Chinese 
      and Western Medicine, Hangzhou, China.
LA  - eng
GR  - Zhejiang Province Traditional Chinese medicine science and technology project/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231101
PL  - England
TA  - Chem Biol Drug Des
JT  - Chemical biology & drug design
JID - 101262549
RN  - 0 (Antioxidants)
RN  - 0 (NF-E2-Related Factor 2)
RN  - RN4CQ46FDM (dixanthogen)
RN  - 0 (Kaempferols)
RN  - 0 (Disulfides)
RN  - 0 (Thiones)
SB  - IM
MH  - Female
MH  - Humans
MH  - Animals
MH  - Mice
MH  - *Antioxidants/pharmacology/therapeutic use
MH  - NF-E2-Related Factor 2
MH  - *Ovarian Reserve/physiology
MH  - Kaempferols/pharmacology/therapeutic use
MH  - *Disulfides
MH  - *Thiones
OTO - NOTNLM
OT  - Er-Xian decoction
OT  - age-related diminished ovarian reserve
OT  - heat shock protein 90
OT  - kaempferol
OT  - nuclear factor erythroid 2-related factor 2
EDAT- 2023/11/02 00:42
MHDA- 2024/01/18 06:42
CRDT- 2023/11/01 21:52
PHST- 2023/10/05 00:00 [revised]
PHST- 2023/06/19 00:00 [received]
PHST- 2023/10/20 00:00 [accepted]
PHST- 2024/01/18 06:42 [medline]
PHST- 2023/11/02 00:42 [pubmed]
PHST- 2023/11/01 21:52 [entrez]
AID - 10.1111/cbdd.14385 [doi]
PST - ppublish
SO  - Chem Biol Drug Des. 2024 Jan;103(1):e14385. doi: 10.1111/cbdd.14385. Epub 2023 
      Nov 1.