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 | ||||
Isotalatizidine | Female C57BL/6 mice BV2 microglial cells Primary microglial cells | 0.1/0.3/1.0 mg/kg i.t 25 μM(in vitro) | ↓Mechanical allodynia | ↑Fluorescence intensity Dynorphin A in spinal cord | – | ↑p-CREB, p-ERK1/2, dynorphin A in the spinal cord tissue ↑prodynorphin mRNA | [25] |
Gelsenicine | Male ICR mice | 0.8/4/20 mg/kg s.c | ↓Thermal hypersensitivity | – | – | – | [26] |
Dehydrocrenatidine | Male Sprague–Dawley rats Primary DRG neurons | 50/150/250 µg/kg i.t | ↓Mechanical allodynia | – | ↓TTX-S and TTX-R currents in DRG | – | [101] |
Matrine | Male ICR mice | 7.5/15/30 mg/kg i.p 8 days | ↓Mechanical allodynia, cold allodynia and thermal hyperalgesia  → Motor coordination  → Spontaneous locomotor | – | – | – | [95] |
Guanfu Base A | Male Sprague Dawley rats HEK293 cells | 40 mg/kg i.p 14 days | ↓Mechanical and thermal hyperalgesia | ↓Co-expression values of P2Y12 and GFAP | – | ↓The expression of P2Y12 mRNA, P2Y12 protein, TNF-α and p-p38 MAPK in L4 –L6 DRGs ↓ADP-induced cAMP concentration in HEK293 cell | [96] |
Sinomenine | Male Sprague–Dawley rats | 10/20/40 mg/kg i.p 2 weeks | ↓Mechanical allodynia ↓Depressive like behavior ↓Locomotor coordination | – | – | – | [97] |
Levo-tetrahydropalmatine | Male ICR mice | 20 nmol i.p 2 nmol i.t | ↓Percentage withdrawal response frequency  → Motor coordination | – | – | ↓pNR1 in spinal dorsal horn | [98] |
Berberine | Male Sprague–Dawley rats | 5/10/20 mg/kg i.p | ↓ Mechanical allodynia and cold allodynia Berberine does not induce sedation |  |  | ↓MPO, MDA in Sciatic nerve | [99] |
Brucine | Male C57BL/6 mice | 10/30 mg/kg | ↓Thermal hypersensitivity and mechanical allodynia | – | ↓Action potential (AP) firing activity of DRG neurons ↓TTX-r and TTX-s currents | – | [100] |
Isorhynchophylline | Adult maleC57BL/6 J mice | 5/15/45 mg/kg i.g Twice per day for 14 days | ↓Tactile allodynia and thermal  → Motor coordination ↓Depression and anxiety like behavior | – | – | ↑5-HT, NA  → 5-HIAA, DA, DOPAC ↓5-HIAA/5-HT ratio, MAO-A | [103] |
Oxymatrine | Male ICR mice | 40/80/160 mg/kg i.p | ↓Mechanical allodynia, cold allodynia and thermal hyperalgesia | ↓ NR2B expression in the superficial dorsal horn | – | ↓GAT-1 in spinal cord ↑GABAARα2 | [109] |
Oxymatrine | Male ICR mice | 40/80/160 mg/kg i.p | ↓Mechanical allodynia and thermal hyperalgesia | ↑Immunostaining positive neurons of GABAAa2 ↓Immunostaining positive neurons of GAT-1 | – | ↓NR2B, p-ERK, p-CREB in spinal cord | [115] |
Koumine | Male Sprague–Dawley rats Microglial BV2 Microglia | 0.28/1.4/7 mg/kg s.c 7 days 25/50/100/200 μg/ml (in vitro) | ↓Mechanical allodynia | ↓ The fluorescence density of Iba-1, GFAP and TSPO expression in the spinal cord | – | ↓IL-1β, TNF-α and TSPO in the spinal cord ↓ LPS-induced the protein levels and the mRNA expression of M1 markers (CD86, IL-6, IL-1β, and TNF-α) in BV2 cells | [102] |
Koumine | Male Sprague–Dawley rats | 0.28/1.4/7 mg/kg s.c twice per day for 7 days | ↓Thermal hyperalgesia and mechanical allodynia | – | – | ↑ Allopregnanolone  → pregnenolone | [130] |
Koumine | Male adult Sprague–Dawley rats | 0.28/1.4/7 mg/kg s.c twice per day for 7 days | ↓Hyperalgesia and allodynia | ↑Fluorescence density of 3α‑HSOR in the ipsilateral dorsal horn of the lumbar spinal cord (L5–L6) | – | ↑ The level of 3α‑HSOR mRNA and 3α‑HSOR catalytic activity in the spinal cord lumbar region L5–L6 | [131] |