PMID- 36460131
OWN - NLM
STAT- MEDLINE
DCOM- 20221219
LR  - 20221221
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 938
DP  - 2023 Jan 5
TI  - Aucubin supplementation alleviate diabetes induced-disruption of blood-testis 
      barrier and testicular damage via stabilizing cell junction integrity.
PG  - 175430
LID - S0014-2999(22)00691-4 [pii]
LID - 10.1016/j.ejphar.2022.175430 [doi]
AB  - Disruption of blood-testis barrier (BTB) was a crucial pathological feature of 
      diabetes induced-testicular injury at early phase. Aucubin (AU), a main active 
      component in Eucommiae Cortex, has drawn attention for its benefits against male 
      reproductive system disease. The current study was aimed at investigating the 
      protective role of AU and exploring the underlying mechanism in diabetic model. A 
      murine model of type 2 diabetes mellitus (T2DM) was induced by high-fat diet 
      (HFD) combined with streptozocin (STZ). Testicular weight index and morphology, 
      sperm quality, integrity of BTB and protein levels were analyzed. The underlying 
      mechanism of the protective effect of AU was further explored in Sertoli cells 
      (SCs) cultured with high glucose (HG). Our results showed AU inhibited testicular 
      structural destruction, restored disruption of BTB and improved abnormal 
      spermatogenic function in diabetic mice. Consistent with in vivo results, HG 
      induced decreased transcellular resistance and increased permeability in SCs 
      monolayers, while AU exposure reverses this trend. Meanwhile, reduced expression 
      of Zonula occludin-1(ZO-1) and Connexin43(Cx43) in testicular tissue diabetic 
      mice and HG-induced SCs was prominently reversed via AU treatment. Mechanistic 
      studies suggested a high affinity interaction between AU and c-Src protein was 
      identified based on molecular docking, and the activation of c-Src was 
      significantly inhibited in AU treatment. Furthermore, AU significantly increased 
      the expression of Cx43 and ZO-1 proteins HG-induced SCs, which can be further 
      enhanced in gene-silenced c-Src cells to some extent. Our results suggested that 
      AU ameliorated disruption of BTB and spermatogenesis dysfunction in diabetic mice 
      via inactivating c-Src to stabilize cell junction integrity.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Wei, Jingxun
AU  - Wei J
AD  - School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 210009, 
      People's Republic of China.
FAU - Lu, Xuanzhao
AU  - Lu X
AD  - School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 210009, 
      People's Republic of China.
FAU - Bao, Xiaowen
AU  - Bao X
AD  - School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 210009, 
      People's Republic of China.
FAU - Zhang, Chi
AU  - Zhang C
AD  - Nanjing Tech University School of Economics & Management. Nanjing Tech 
      University, Nanjing, 210009, People's Republic of China.
FAU - Li, Jiaqi
AU  - Li J
AD  - School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 210009, 
      People's Republic of China.
FAU - Ren, Chaoxing
AU  - Ren C
AD  - School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 210009, 
      People's Republic of China.
FAU - Zhu, Zhiming
AU  - Zhu Z
AD  - School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 210009, 
      People's Republic of China.
FAU - Ma, Beiting
AU  - Ma B
AD  - School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 210009, 
      People's Republic of China.
FAU - Zhang, Nan
AU  - Zhang N
AD  - School of Chemical and Molecular Engineering, Nanjing Tech University, Nanjing, 
      People's Republic of China.
FAU - Jin, Xin
AU  - Jin X
AD  - School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 210009, 
      People's Republic of China.
FAU - Ma, Bo
AU  - Ma B
AD  - School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, 210009, 
      People's Republic of China. Electronic address: mabo201012@njtech.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20221129
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 2G52GS8UML (aucubin)
RN  - 0 (Connexin 43)
SB  - IM
MH  - Male
MH  - Mice
MH  - Animals
MH  - Blood-Testis Barrier/metabolism/pathology
MH  - Connexin 43/metabolism
MH  - *Diabetes Mellitus, Experimental/metabolism
MH  - *Diabetes Mellitus, Type 2/metabolism
MH  - Molecular Docking Simulation
MH  - Semen/metabolism
MH  - Testis
MH  - Sertoli Cells/metabolism
MH  - Intercellular Junctions/metabolism
MH  - Dietary Supplements
OTO - NOTNLM
OT  - Aucubin
OT  - Blood-testis barrier (BTB)
OT  - Cx43
OT  - Diabetes
OT  - Sertoli cells (SCs)
OT  - c-Src
COIS- Declaration of competing interest The authors declare no conflict of interest.
EDAT- 2022/12/03 06:00
MHDA- 2022/12/20 06:00
CRDT- 2022/12/02 19:24
PHST- 2022/04/30 00:00 [received]
PHST- 2022/11/23 00:00 [revised]
PHST- 2022/11/24 00:00 [accepted]
PHST- 2022/12/03 06:00 [pubmed]
PHST- 2022/12/20 06:00 [medline]
PHST- 2022/12/02 19:24 [entrez]
AID - S0014-2999(22)00691-4 [pii]
AID - 10.1016/j.ejphar.2022.175430 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2023 Jan 5;938:175430. doi: 10.1016/j.ejphar.2022.175430. Epub 
      2022 Nov 29.