PMID- 31360147
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1559-3258 (Print)
IS  - 1559-3258 (Electronic)
IS  - 1559-3258 (Linking)
VI  - 17
IP  - 3
DP  - 2019 Jul-Sep
TI  - Ameliorative Effect of Berberine on Neonatally Induced Type 2 Diabetic Neuropathy 
      via Modulation of BDNF, IGF-1, PPAR-gamma, and AMPK Expressions.
PG  - 1559325819862449
LID - 10.1177/1559325819862449 [doi]
LID - 1559325819862449
AB  - Neonatal-streptozotocin (n-STZ)-induced diabetes mimics most of the 
      clinicopathological symptoms of type 2 diabetes mellitus (T2DM) peripheral 
      neuropathy. Berberine, a plant alkaloid, is reported to have antidiabetic, 
      antioxidant, anti-inflammatory, and neuroprotective potential. The aim of the 
      present study was to investigate the potential of berberine against n-STZ-induced 
      painful diabetic peripheral polyneuropathy by assessing various biochemical, 
      electrophysiological, morphological, and ultrastructural studies. Type 2 diabetes 
      mellitus was produced neonatal at the age of 2 days (10-12 g) by STZ (90 mg/kg 
      intraperitoneal). After confirmation of neuropathy at 6 weeks, rats were treated 
      with berberine (10, 20, and 40 mg/kg). Administration of n-STZ resulted in 
      T2DM-induced neuropathic pain reflected by a significant alterations (P < .05) in 
      hyperalgesia, allodynia, and motor as well as sensory nerve conduction velocities 
      whereas berberine (20 and 40 mg/kg) treatment significantly attenuated (P < .05) 
      these alterations. Berberine treatment significantly inhibited (P < .05) 
      STZ-induced alterations in aldose reductase, glycated hemoglobin, serum insulin, 
      hepatic cholesterol, and triglyceride levels. The elevated oxido-nitrosative 
      stress and decreased Na-K-ATPase and pulse Ox levels were significantly 
      attenuated (P < .05) by berberine. It also significantly downregulated (P < .05) 
      neural tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-6 messenger 
      RNA (mRNA), and protein expressions both. Streptozotocin-induced downregulated 
      mRNA expressions of brain-derived neurotrophic factor (BDNF), insulin-like growth 
      factor (IGF-1), and peroxisome proliferator-activated receptors-gamma (PPAR-gamma) in 
      sciatic nerve were significantly upregulated (P < .05) by berberine. Western blot 
      analysis revealed that STZ-induced alterations in adenosine monophosphate protein 
      kinase (AMPK; Thr-172) and protein phosphatase 2C-alpha protein expressions in dorsal 
      root ganglia were inhibited by berberine. It also attenuated histological and 
      ultrastructural alterations induced in sciatic nerve by STZ. In conclusion, 
      berberine exerts its neuroprotective effect against n-STZ-induced diabetic 
      peripheral neuropathy via modulation of pro-inflammatory cytokines (TNF alpha, IL-1beta, 
      and IL-6), oxido-nitrosative stress, BDNF, IGF-1, PPAR-gamma, and AMPK expression to 
      ameliorate impaired allodynia, hyperalgesia, and nerve conduction velocity during 
      T2DM.
FAU - Zhou, Guangju
AU  - Zhou G
AD  - Department of Endocrinology and Metabolism, West China Hospital of Sichuan 
      University, Chengdu, China.
FAU - Yan, Mingzhu
AU  - Yan M
AD  - Department of Neurology, Xijing Hospital, Fourth Military Medical University 
      (FMMU), Shaanxi, China.
FAU - Guo, Gang
AU  - Guo G
AD  - Department of Talent Highland, Department of General Surgery, The First 
      Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, China.
FAU - Tong, Nanwei
AU  - Tong N
AUID- ORCID: 0000-0001-7072-3480
AD  - Department of Endocrinology and Metabolism, West China Hospital of Sichuan 
      University, Chengdu, China.
LA  - eng
PT  - Journal Article
DEP - 20190716
PL  - United States
TA  - Dose Response
JT  - Dose-response : a publication of International Hormesis Society
JID - 101308899
PMC - PMC6636227
OTO - NOTNLM
OT  - 5'-adenosine monophosphate-activated protein kinase
OT  - berberine
OT  - brain-derived neurotrophic factor
OT  - diabetic neuropathy
OT  - insulin-like growth factor-1
OT  - neonatal-streptozotocin
OT  - peroxisome proliferator-activated receptors-gamma
OT  - type 2 diabetes
COIS- Declaration of Conflicting Interests: The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2019/07/31 06:00
MHDA- 2019/07/31 06:01
PMCR- 2019/07/16
CRDT- 2019/07/31 06:00
PHST- 2019/04/18 00:00 [received]
PHST- 2019/06/15 00:00 [revised]
PHST- 2019/06/18 00:00 [accepted]
PHST- 2019/07/31 06:00 [entrez]
PHST- 2019/07/31 06:00 [pubmed]
PHST- 2019/07/31 06:01 [medline]
PHST- 2019/07/16 00:00 [pmc-release]
AID - 10.1177_1559325819862449 [pii]
AID - 10.1177/1559325819862449 [doi]
PST - epublish
SO  - Dose Response. 2019 Jul 16;17(3):1559325819862449. doi: 10.1177/1559325819862449. 
      eCollection 2019 Jul-Sep.