# Licorice extract and carbenoxolone protect PC12 cells against serum/glucose deprivation-induced apoptosis through modulation of caspase-3 and PARP activation

**Authors:** Hossein Hosseinzadeh, Elham Ramazani, Soheyla Bakhshi, Zahra Tayarani-Najaran

PMC · DOI: 10.22038/ajp.2024.25252 · Avicenna Journal of Phytomedicine · 2025-07-01

## TL;DR

Licorice extract and carbenoxolone protect brain-like cells from damage caused by lack of nutrients, possibly helping in treating brain ischemia.

## Contribution

The study demonstrates licorice extract and carbenoxolone's anti-apoptotic effects in a model of brain injury.

## Key findings

- Licorice extract and carbenoxolone reduced cell death and ROS in PC12 cells under stress.
- Pretreatment inhibited PARP and caspase-3 cleavage, indicating anti-apoptotic activity.
- Low concentrations of licorice extract and carbenoxolone showed significant protective effects.

## Abstract

Serum/glucose deprivation in cultured PC12 cells is considered an appropriate model for investigating detailed mechanisms of ischemia-induced brain injury. Here, we aimed to study the anti-apoptotic effects of licorice (Glycyrrhiza glabra L.) root extract and carbenoxolone on PC12 cells cultured in the serum/glucose deprivation (SGD) condition.

Cells were incubated with the different concentrations of the G. glabra methanol extract (5-320 µg/ml) and carbenoxolone (0.5-32 µM) for 2 hr before being deprived of serum/glucose. Protection against cytotoxicity, increase in reactive oxygen species (ROS), and apoptosis was analyzed with resazurin, dichlorofluorescein diacetate (DCFH-DA), and western blot, respectively.

Serum/glucose deprivation induced cell death and apoptosis in PC12 cells. Pretreatment with the G. glabra methanol extract at 5-20 µg/ml and carbenoxolone at 0.5-2 µM for 2 hr significantly decreased the cytotoxicity (p<0.05), and pretreatment with the G. glabra methanol extract (5-160 µg/ml) and carbenoxolone (0.5 μM) significantly decreased the ROS content. Pretreatment with the G. glabra methanol extract and carbenoxolone at 5-20 µg/ml significantly prevented from the Poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavage.

Taken together, this study confirms the protective and free radical-scavenging potency of licorice extract and carbenoxolone in in vitro model of ischemia. Overall, it seems that pretreatment with the licorice extract and carbenoxolone may potentially slow the progression of brain ischemia.

## Linked entities

- **Proteins:** PARP1 (poly(ADP-ribose) polymerase 1), Casp3 (caspase 3)
- **Chemicals:** carbenoxolone (PubChem CID 636403), resazurin (PubChem CID 11077), dichlorofluorescein diacetate (PubChem CID 101615877), DCFH-DA (PubChem CID 104913)
- **Diseases:** brain ischemia (MONDO:0005299)

## Full-text entities

- **Diseases:** brain ischemia (MESH:D002545), ischemia (MESH:D007511), brain injury (MESH:D001930), cytotoxicity (MESH:D064420)
- **Chemicals:** ROS (MESH:D017382), dichlorofluorescein diacetate (-), DCFH-DA (MESH:C029569), resazurin (MESH:C005843), glucose (MESH:D005947), carbenoxolone (MESH:D002229)
- **Species:** Glycyrrhiza glabra (species) [taxon 49827]
- **Cell lines:** PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12244954/full.md

## References

58 references — full list in the complete paper: https://tomesphere.com/paper/PMC12244954/full.md

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Source: https://tomesphere.com/paper/PMC12244954