PMID- 38519940
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240325
IS  - 1749-8546 (Print)
IS  - 1749-8546 (Electronic)
IS  - 1749-8546 (Linking)
VI  - 19
IP  - 1
DP  - 2024 Mar 22
TI  - Total iridoid glycoside extract of Lamiophlomis rotata (Benth) Kudo accelerates 
      diabetic wound healing by the NRF2/COX2 axis.
PG  - 53
LID - 10.1186/s13020-024-00921-1 [doi]
LID - 53
AB  - BACKGROUND: Lamiophlomis rotata (Benth.) Kudo (L. rotata), the oral Traditional 
      Tibetan herbal medicine, is adopted for treating knife and gun wounds for a long 
      time. As previously demonstrated, total iridoid glycoside extract of L. rotata 
      (IGLR) induced polarization of M2 macrophage to speed up wound healing. In 
      diabetic wounds, high levels inflammatory and chemotactic factors are usually 
      related to high reactive oxygen species (ROS) levels. As a ROS target gene, 
      nuclear factor erythroid 2-related factor 2 (NRF2), influences the 
      differentiation of monocytes to M1/M2 macrophages. Fortunately, iridoid 
      glycosides are naturally occurring active compounds that can be used as the 
      oxygen radical scavenger. Nevertheless, the influence of IGLR in diabetic wound 
      healing and its associated mechanism is largely unclear. MATERIALS AND METHODS: 
      With macrophages and dermal fibroblasts in vitro, as well as a thickness excision 
      model of db/db mouse in vivo, the role of IGLR in diabetic wound healing and the 
      probable mechanism of the action were investigated. RESULTS: Our results showed 
      that IGLR suppressed oxidative distress and inflammation partly through the 
      NRF2/cyclooxygenase2 (COX2) signaling pathway in vitro. The intercellular 
      communication between macrophages and dermal fibroblasts was investigated by the 
      conditioned medium (CM) of IGLR treatment cells. The CM increased the 
      transcription and translation of collagen I (COL1A1) and alpha smooth muscle 
      actin (alpha-SMA) within fibroblasts. With diabetic wound mice, the data demonstrated 
      IGLR activated the NRF2/KEAP1 signaling and the downstream targets of the 
      pathway, inhibited COX2/PEG2 signaling and decreased the interaction inflammatory 
      targets of the axis, like interleukin-1beta (IL-1beta), interleukin 6 (IL-6), 
      apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific 
      proteinase1 (caspase1) and NOD-like receptor-containing protein 3 (NLRP3).In 
      addition, the deposition of COL1A1, and the level of alpha-SMA, and Transforming 
      growth factor-beta1 (TGF-beta1) obviously elevated, whereas that of pro-inflammatory 
      factors reduced in the diabetic wound tissue with IGLR treatment. CONCLUSION: 
      IGLR suppressed oxidative distress and inflammation mainly through NRF2/COX2 
      axis, thus promoting paracrine and accelerating wound healing in diabetes mice.
CI  - (c) 2024. The Author(s).
FAU - Geng, Xiaoyu
AU  - Geng X
AD  - College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 
      China.
FAU - Wang, Ying
AU  - Wang Y
AD  - College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 
      China.
FAU - Li, Huan
AU  - Li H
AD  - College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 
      China.
FAU - Song, Liang
AU  - Song L
AD  - College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 
      China.
FAU - Luo, Chen
AU  - Luo C
AD  - College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 
      China.
FAU - Gu, Xiaojie
AU  - Gu X
AD  - College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 
      China.
FAU - Zhong, Haixin
AU  - Zhong H
AD  - College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 
      China.
FAU - Chen, Huilin
AU  - Chen H
AD  - College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 
      China.
FAU - Chen, Xinzhu
AU  - Chen X
AD  - College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 
      China.
FAU - Wang, Jianwei
AU  - Wang J
AD  - College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 
      China.
AD  - Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure 
      of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical 
      University, No.1, Yixueyuan Road, Chongqing, China.
FAU - Pan, Zheng
AU  - Pan Z
AUID- ORCID: 0000-0002-9727-7975
AD  - College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 
      China. 102796@cqmu.edu.cn.
AD  - Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure 
      of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical 
      University, No.1, Yixueyuan Road, Chongqing, China. 102796@cqmu.edu.cn.
LA  - eng
GR  - 81973567/National Natural Science Foundation of China/
GR  - cstc2022ycjh bgzxm0010/Chongqing Municipal Youth Science and Technology Talent 
      Training Project/
PT  - Journal Article
DEP - 20240322
PL  - England
TA  - Chin Med
JT  - Chinese medicine
JID - 101265109
PMC - PMC10960394
OTO - NOTNLM
OT  - Lamiophlomis rotata
OT  - Diabetic wound healing
OT  - Iridoid glycoside
OT  - NRF2/COX2 axis
COIS- We claim no conflicts of interest.
EDAT- 2024/03/23 20:44
MHDA- 2024/03/23 20:45
PMCR- 2024/03/22
CRDT- 2024/03/23 01:26
PHST- 2023/12/01 00:00 [received]
PHST- 2024/03/08 00:00 [accepted]
PHST- 2024/03/23 20:45 [medline]
PHST- 2024/03/23 20:44 [pubmed]
PHST- 2024/03/23 01:26 [entrez]
PHST- 2024/03/22 00:00 [pmc-release]
AID - 10.1186/s13020-024-00921-1 [pii]
AID - 921 [pii]
AID - 10.1186/s13020-024-00921-1 [doi]
PST - epublish
SO  - Chin Med. 2024 Mar 22;19(1):53. doi: 10.1186/s13020-024-00921-1.