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Table 3 Effects of alkaloids on diabetic painful neuropathy (DPN)

From: Effects of alkaloids on peripheral neuropathic pain: a review

Alkaloids Animal/cell Dose mg/kg (route of administration) Effects/mechanisms of action References
Behavioral evaluation Histopathological observation Electrophysiology parameters Biochemical/Molecular parameters/mRNA
Koumine Male Sprague–Dawley rats 0.056/0.28/1.4/7 mg/kg
7 days
 → Blood glucose and body weight
↓Streptozotocin-induced mechanical allodynia
↑Myelin thickness, axon diameter and number of myelinated nerve fibers ↑SNCV [27]
Berberine Adult male and female Sprague–Dawley rats 10/20/40 mg/kg
8 days
↓Streptozotocin-induced mechanical allodynia and thermal hyperalgesia ↓Necrosis, edema, inflammatory infiltration, and congestion after intraperitoneal administration of STZ in sciatic nerve
↓Split and disintegrated neurofilaments and swoln axonal mitochondria
↑MNCV and SNCV Reverse Streptozotocin-induced oxido-nitrosative stress (SOD, GSH, MDA, and NO) and Na+K+-ATPase alteration
↑BDNF, IGF-1, PPAR-γ, IL-6, IL-1β and TNF-α
Berberine Male C57BL/6 mice The dose was not mentioned
14 days
↓Streptozotocin-induced mechanical allodynia and thermal hyperalgesia ↓The relative Iba-1-positive area and GFAP-positive area reflected by the Iba-1 and GFAP fluorescence density after the treatment of berberine in spinal cord slices ↓The expression of TNF-α, IL-6, IL-1β, iNOS and COX-2 in spinal cord and DRG [41]
Sinomenine Male Sprague–Dawley rats HEK293 cells 40 mg/kg
10 Μm(in vitro)
↓Streptozotocin -induced thermal hyperalgesia and mechanical hyperalgesia ↓ATP-activated current in HEK293 cells transfected with the pEGFP-hP2X3 plasmid ↓p-P38MAPK and P2X3 protein in DRG
↓P2X3 mRNA in DRG
[44, 64]
Palmatine Male Sprague- Dawley rats 30 mg/kg
14 days
↓Streptozotocin-induced mechanical hyperalgesia and thermal hyperalgesia
↓Depressive like behavior
↓Fluorescence intensity of co-localization of P2X7 and GFAP in the hippocampus
↓Positive signal of P2X7 protein in the hippocampus
↓P2X7, TNF-α and IL-1β mRNA
↓p-ERK1/2 in the hippocampus
Bullatine A Male adult Wistar rats 0.3/1/3/10/30 mg/kg
0.3/1/3/10/30 μg
↓Mechanical allodynia and thermal hyperalgesia [45]
  1. ↑: Enhanced/Increased/Upregulate↓: Attenuate/Downregulate/Decrease/Suppress/Inhibit/Prevent