Goldenseal (Hydrastis canadensis) 43525850
Inhibition of organic cation transporter 2 and 3 may be involved in the mechanism of the antidepressant-like action of berberine CSV JSON

Organic cation transporter 2 (OCT2) and 3 (OCT3) are low-affinity, high-capacity transporters (uptake-2) expressed in the central nervous system (CNS) and other major organs. Proven to be essential components in the CNS functions, OCT2 and OCT3 are suggested as potential targets of antidepressant therapeutics recently. Berberine, an active constituent derived from many medicinal plants, such as Coptis chinensis, has been reported to possess antidepressant-like action in the tail suspension test and forced swim test with elevated serotonin/ norepinephrine/dopamine (5-HT/NE/DA) level in mouse brain; however the mechanism has not been elucidated. In consideration of the relation between OCT2/3 and antidepressant action, and the characteristic of berberine as an organic cation, we investigated the potential involvement of OCT2 and OCT3 in the antidepressant-like action of berberine in the present study. The results in mouse brain synaptosomes demonstrated that uptake-2 inhibition might play a notable role in enhanced serotonergic and noradrenergic effects induced by berberine. The inhibitory study in transfected MDCK cells displayed that berberine is a potent inhibitor of human OCT2 and OCT3, and its IC50values for inhibition of transporter-mediated 5-HT/NE uptake are between 0.1 and 1 μM. In addition, berberine was identified as a substrate of hOCT2 and hOCT3. In conclusion, berberine is a substrate and an inhibitor of hOCT2 and hOCT3, and its inhibition on OCT2- and OCT3-mediated 5-HT and NE uptake may contribute to the enhanced monoamine neurotransmission in mouse brain. It was deduced that the inhibition of OCT2 and OCT3 probably be implicated in the mechanism of antidepressant-like action.

1 . OCT2 Inhibition by Berberine (NE) (id=NPDI-rR-2qg)

In Vitro Transporter Inhibition Experiment

Inhibition was detected.  Cutoff used — not specified

norepinephrine

Berberine 19012197

  • OCT2 (SLC22A2)

Transfected / siRNA knock-out / injected cells MDCK transfected cells

Results

Table 2
Final value in Fig 4

Compound measured Measurement Value Study sequence Additional information N replicates

Experimental Conditions

Cell Culture Conditions

24 well

2-3

Assay Conditions

20 min

37 deg C

200 μM

0.0001 to 1000 μM

Aladdin Co., Ltd. (Shanghai, China)

2 . OCT2 Inhibition by Berberine (5-HT) (id=NPDI-gJxFZQ)

In Vitro Transporter Inhibition Experiment

Inhibition was detected.  Cutoff used — not specified

serotonin

Berberine 19012197

  • OCT2 (SLC22A2)

Transfected / siRNA knock-out / injected cells MDCK transfected cells

Results

Table 2
Fig 3a final point estimate

Compound measured Measurement Value Study sequence Additional information N replicates

Experimental Conditions

Cell Culture Conditions

24 well

2-3

Assay Conditions

5 min

37 deg C

10 μM

0.0001 to 1000 μM

Aladdin Co., Ltd. (Shanghai, China)

1 . Berberine Transport by OCT2 (id=NPDI-5R4-8g)

In Vitro Transporter Kinetics Experiment

Transport Activity was detected.  Cutoff used — not specified

Berberine 19012197

  • OCT2 (SLC22A2)

Transfected / siRNA knock-out / injected cells MDCK transfected cells

Results

Fig 5 estimate of uptake at 10 min (accumulation)

Fig. 6. Concentration-dependent uptake of berberine mediated by hOCT2 or hOCT3. Up- take was carried out in parallel in mock, hOCT2- and hOCT3-transfected MDCK cells. Up- take in mock cells was subtracted from hOCT2 or hOCT3 cells to obtain transporter- specific uptake. The uptake was performed within 2 min. Data are expressed as mean ± SD (n = 3).

Compound measured Measurement Value Study sequence Additional information N replicates

Experimental Conditions

Cell Culture Conditions

24 well

2-3

Assay Conditions

2 min

37 deg C

0.25-25 μM