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Table 5 Effects of alkaloids on sciatic nerve chronic constriction injury (CCI)

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]

  1. ↑: Enhanced/Increased/Upregulate↓: Attenuate/Downregulate/Decrease/Suppress/Inhibit/Prevent