PMID- 34987398
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220107
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Artesunate Combined With Metformin Ameliorate on Diabetes-Induced Xerostomia by 
      Mitigating Superior Salivatory Nucleus and Salivary Glands Injury in Type 2 
      Diabetic Rats via the PI3K/AKT Pathway.
PG  - 774674
LID - 10.3389/fphar.2021.774674 [doi]
LID - 774674
AB  - Polydipsia and xerostomia are the most common complications that seriously affect 
      oral health in patients with diabetes. However, to date, there is no effective 
      treatment for diabetic xerostomia. Recent studies have reported that artesunate 
      (ART) and metformin (Met) improve salivary gland (SG) hypofunction in murine 
      Sjogren's syndrome. Therefore, aim of this study was to investigate the effect 
      and underlying mechanism of artesunate (ART) alone and in combination with 
      metformin (Met) on hyposalivation in type 2 diabetes mellitus (T2DM) rats. T2DM 
      rats were induced using a high-fat diet and streptozotocin. SPF male 
      Sprague-Dawley rats were divided into the following five groups: normal control 
      group, untreated diabetic group, ART-treated diabetic group (50 mg/kg), 
      Met-treated diabetic group (150 mg/kg), and ART/Met co-treated diabetic group 
      (50 mg/kg ART and 150 mg/kg Met). ART and Met were intragastrically administered 
      daily for 4 weeks. The general conditions, diabetes parameters and serum lipids 
      were evaluated after drug treatment. Furthermore, we observed changes in the 
      central superior salivatory nucleus (SSN) and SG, and changes in the AQP5 
      expression, parasympathetic innervation (AChE and BDNF expression), and PI3K/AKT 
      pathway- (p-AKT, and p-PI3K), apoptosis- (Bax, Bcl-2, and Caspase3), and 
      autophagy- (LC3 and P62) related markers expression in T2DM rats after treatment. 
      Our results showed that ART or Met alone and ART/Met combination attenuated a 
      range of diabetic symptoms, including weight loss, urine volume increase, water 
      consumption increase, hyperglycemia, insulin resistance, glucose intolerance and 
      dyslipidemia. More importantly, we found that these three treatments, especially 
      ART/Met combination, mitigated hyposalivation in the T2DM rats via improving the 
      central SSN and SGs damage in hyperglycemia. Our data also indicated that ART/Met 
      attenuated SG damage though regulating the PI3K/Akt pathway to inhibit apoptosis 
      and autophagy of SGs in the T2DM rats. Moreover, ART/Met preserved 
      parasympathetic innervation (AChE and BDNF expression) in SGs to alleviate 
      diabetes-induced hyposalivation likely through rescuing central SSN damage. Taken 
      together, these findings might provide a novel rationale and treatment strategy 
      for future treatment of diabetes-induced xerostomia in the clinic.
CI  - Copyright (c) 2021 Zhang, Li, Nong, Zhan, Xu, Zhao, Ma, Wang, Li, Li and Li.
FAU - Zhang, Siqin
AU  - Zhang S
AD  - College of Stomatology, Guangxi Medical University, Nanning, China.
FAU - Li, Jiarui
AU  - Li J
AD  - College of Stomatology, Guangxi Medical University, Nanning, China.
FAU - Nong, Xiaolin
AU  - Nong X
AD  - College of Stomatology, Guangxi Medical University, Nanning, China.
AD  - Guangxi Key Laboratory of Oral and Maxillofacial Surgery Disease Treatment, 
      Nanning, China.
FAU - Zhan, Yuxiang
AU  - Zhan Y
AD  - College of Stomatology, Guangxi Medical University, Nanning, China.
FAU - Xu, Jiazhi
AU  - Xu J
AD  - College of Stomatology, Guangxi Medical University, Nanning, China.
FAU - Zhao, Danni
AU  - Zhao D
AD  - College of Stomatology, Guangxi Medical University, Nanning, China.
FAU - Ma, Chubin
AU  - Ma C
AD  - College of Stomatology, Guangxi Medical University, Nanning, China.
FAU - Wang, Yuchen
AU  - Wang Y
AD  - College of Stomatology, Guangxi Medical University, Nanning, China.
FAU - Li, Yixing
AU  - Li Y
AD  - College of Stomatology, Guangxi Medical University, Nanning, China.
FAU - Li, Zhan
AU  - Li Z
AD  - College of Stomatology, Guangxi Medical University, Nanning, China.
FAU - Li, Jiaquan
AU  - Li J
AD  - Medical Science Research Center, Guangxi Medical University, Nanning, China.
AD  - Life Science Institute, Guangxi Medical University, Nanning, China.
LA  - eng
PT  - Journal Article
DEP - 20211220
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8722737
OTO - NOTNLM
OT  - PI3K/Akt pathway
OT  - artesunate
OT  - diabetic xerostomia
OT  - metformin
OT  - salivary gland
OT  - superior salivatory nucleus
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/01/07 06:00
MHDA- 2022/01/07 06:01
PMCR- 2021/12/20
CRDT- 2022/01/06 05:52
PHST- 2021/09/12 00:00 [received]
PHST- 2021/11/09 00:00 [accepted]
PHST- 2022/01/06 05:52 [entrez]
PHST- 2022/01/07 06:00 [pubmed]
PHST- 2022/01/07 06:01 [medline]
PHST- 2021/12/20 00:00 [pmc-release]
AID - 774674 [pii]
AID - 10.3389/fphar.2021.774674 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Dec 20;12:774674. doi: 10.3389/fphar.2021.774674. 
      eCollection 2021.