PMID- 34980192
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220107
IS  - 1749-8546 (Print)
IS  - 1749-8546 (Electronic)
IS  - 1749-8546 (Linking)
VI  - 17
IP  - 1
DP  - 2022 Jan 4
TI  - Qingwei San treats oral ulcer subjected to stomach heat syndrome in db/db mice by 
      targeting TLR4/MyD88/NF-kappaB pathway.
PG  - 1
LID - 10.1186/s13020-021-00565-5 [doi]
LID - 1
AB  - BACKGROUND: Qingwei San (QWS), one of classic Chinese Medicine prescripts, has 
      been widely used to treat stomach heat syndrome which manifests oral ulcer (OU), 
      periodontitis and upper gastrointestinal bleeding for seven hundred years. 
      However, the therapeutic effects of QWS on diabetic OU subjected to stomach heat 
      syndrome are still ambiguous. In the study, we investigated the pharmacological 
      mechanisms. METHODS: The main components of QWS aqueous extract were analyzed by 
      LC-MS, and potential pathways of QWS targeting OU were predicted by network 
      pharmacology. The db/db mice were administered with the decoction of dried 
      Zingiber officinale Rosc. rhizome combined with NaOH cauterization to establish 
      the model of diabetic OU subjected to stomach heat syndrome. Subsequently, the 
      model mice were treated with QWS, and OU wound healing status were recorded. The 
      pathological changes of gastric tissue and oral mucosa were evaluated using 
      hematoxylin-eosin staining, and the morphology of collagen fibers in oral mucosa 
      was assessed by Masson staining. The levels of thromboxane B(2) (TXB(2)), 
      6-Keto-prostaglandin F1alpha (6-keto-PGF1alpha), interleukin-1 beta (IL-1beta), IL-2, IL-6, 
      tumor necrosis factor-alpha (TNF-alpha), beta-endorphin (beta-EP) and 5-Hydroxytryptamine 
      (5-HT) were determined by ELISA assay. The protein expressions of Toll-like 
      receptor 4 (TLR4), TNF receptor associated factor 6 (TRAF6), myeloid 
      differentiation factor 88 (MyD88), inhibitor of NF-kappaB alpha (IkappaBetaalpha), p-IkappaBetaalpha and 
      nuclear factor kappa-B (NF-kappaB) p65 were measured by Western Blotting. RESULTS: A 
      total of 183 compounds in QWS were identified by LC-MS, and identified 79 
      bioactive compounds corresponded to 269 targets and 59 pathways. QWS high-dose 
      treatment significantly reduced the level of TXB(2) and the ratio of 
      TXB(2)/6-keto-PGF1alpha. Meanwhile, it improved mucosal pathological morphology, and 
      reduced the area of OU and local edema. Simultaneously, the levels of TNF-alpha, 
      IL-1beta, IL-6, IL-2 and 5-HT, and the expressions of TLR4, TRAF6, MyD88, p-IkappaBetaalpha and 
      NF-kappaB p65 were decreased. CONCLUSION: QWS treatment facilitates the healing of 
      OU, ameliorates pathological morphologies of gastric and oral mucosa and 
      decreases the levels of pro-inflammatory cytokines in db/db mice subjected to 
      stomach heat syndrome, whose mechanism may be associated with the inhibition of 
      TLR4/MyD88/NF-kappaB signaling pathway to exert anti-inflammatory effects.
CI  - (c) 2021. The Author(s).
FAU - Shi, Lu
AU  - Shi L
AD  - Department of Pharmacology, School of Chinese Materia Medica, Beijing University 
      of Chinese Medicine, Beijing, 102488, China.
FAU - An, Yongcheng
AU  - An Y
AD  - School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, 
      China.
FAU - Cheng, Long
AU  - Cheng L
AD  - Department of Pharmacology, School of Chinese Materia Medica, Beijing University 
      of Chinese Medicine, Beijing, 102488, China.
FAU - Li, Yiyang
AU  - Li Y
AD  - Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research 
      in Chinese Medicine, University of Macau, Research Building N22, Avenida da 
      Universidade, Taipa, Macao SAR, 999078, China.
FAU - Li, Huimin
AU  - Li H
AD  - Department of Pharmacology, School of Chinese Materia Medica, Beijing University 
      of Chinese Medicine, Beijing, 102488, China.
FAU - Wang, Chen
AU  - Wang C
AD  - School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, 
      China.
FAU - Lv, Yinglan
AU  - Lv Y
AD  - Department of Pharmacology, School of Chinese Materia Medica, Beijing University 
      of Chinese Medicine, Beijing, 102488, China.
FAU - Duan, Yuhui
AU  - Duan Y
AD  - Department of Pharmacology, School of Chinese Materia Medica, Beijing University 
      of Chinese Medicine, Beijing, 102488, China.
FAU - Dai, Hongyu
AU  - Dai H
AD  - Department of Pharmacology, School of Chinese Materia Medica, Beijing University 
      of Chinese Medicine, Beijing, 102488, China.
FAU - He, Changhao
AU  - He C
AD  - Department of Pharmacology, School of Chinese Materia Medica, Beijing University 
      of Chinese Medicine, Beijing, 102488, China.
FAU - Zhang, Huilin
AU  - Zhang H
AD  - Department of Pharmacology, School of Chinese Materia Medica, Beijing University 
      of Chinese Medicine, Beijing, 102488, China.
FAU - Huang, Yan
AU  - Huang Y
AD  - School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, 
      China.
FAU - Fu, Wanxin
AU  - Fu W
AD  - School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, 
      China.
FAU - Wang, ShengPeng
AU  - Wang S
AD  - Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research 
      in Chinese Medicine, University of Macau, Research Building N22, Avenida da 
      Universidade, Taipa, Macao SAR, 999078, China.
FAU - Zhao, Baosheng
AU  - Zhao B
AD  - Beijing Research Institute of Chinese Medicine, Beijing University of Chinese 
      Medicine, No. 11 North 3rd Ring East Road, Chao-Yang District, Beijing, 100029, 
      China. zhaobs1973@163.com.
FAU - Wang, Yitao
AU  - Wang Y
AD  - Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research 
      in Chinese Medicine, University of Macau, Research Building N22, Avenida da 
      Universidade, Taipa, Macao SAR, 999078, China.
FAU - Zhao, Yonghua
AU  - Zhao Y
AUID- ORCID: 0000-0001-8714-0476
AD  - Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research 
      in Chinese Medicine, University of Macau, Research Building N22, Avenida da 
      Universidade, Taipa, Macao SAR, 999078, China. Yonghuazhao@um.edu.mo.
LA  - eng
GR  - 007/2020/ALC/the Science and Technology Development Fund/
GR  - 2019B030302005/Major basic and applied basic research projects of Guangdong 
      Province of China/
GR  - 81973535/National Natural Science Foundation of China/
GR  - 81773960/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20220104
PL  - England
TA  - Chin Med
JT  - Chinese medicine
JID - 101265109
PMC - PMC8725453
OTO - NOTNLM
OT  - Diabetes mellitus
OT  - Oral ulcer
OT  - Qingwei San
OT  - Stomach heat syndrome
OT  - TLR4/MyD88/NF-kappaB
COIS- The authors declare that they have no competing interests.
EDAT- 2022/01/05 06:00
MHDA- 2022/01/05 06:01
PMCR- 2022/01/04
CRDT- 2022/01/04 05:46
PHST- 2021/10/25 00:00 [received]
PHST- 2021/12/28 00:00 [accepted]
PHST- 2022/01/04 05:46 [entrez]
PHST- 2022/01/05 06:00 [pubmed]
PHST- 2022/01/05 06:01 [medline]
PHST- 2022/01/04 00:00 [pmc-release]
AID - 10.1186/s13020-021-00565-5 [pii]
AID - 565 [pii]
AID - 10.1186/s13020-021-00565-5 [doi]
PST - epublish
SO  - Chin Med. 2022 Jan 4;17(1):1. doi: 10.1186/s13020-021-00565-5.