Therapeutic potential of andrographolide for treating endometriosis.

Abstract

BACKGROUND:

Mounting evidence shows that nuclear factor-κB (NF-κB) plays an important role in endometriosis. We therefore evaluated the therapeutic potential of andrographolide, an NF-κB inhibitor.

METHODS:

Primary cell cultures were performed using ectopic endometrial tissue specimens and their homologous eutopic endometrial specimens from 16 women with endometriosis, as well as control samples from 4 women without endometriosis. Andrographolide was evaluated for an effect on cell proliferation and cell cycle, DNA-binding activity of NF-κB and expression of cyclooxygenase-2 (COX-2) and tissue factor (TF). In a rat model of endometriosis, andrographolide treatment was evaluated for an effect on lesion size, hotplate response latency and expression of phosphorylated p50 and p65, COX-2 and nerve growth factor (NGF) in ectopic endometrium.

RESULTS:

Andrographolide dose dependently suppressed proliferation and cell cycle progression, attenuated DNA-binding activity of NF-κB in endometriotic stromal cells and inhibited COX-2 and TF expression. In the rat experiment, induced endometriosis resulted in reduced response latency. Andrographolide treatment significantly reduced lesion size in a dose-dependent manner and significantly increased response latency. Andrographolide treatment also significantly reduced immunoreactivity of COX-2, phosphorylated p50 and p65, and NGF in ectopic endometrium.

CONCLUSIONS:

Treatment with andrographolide significantly suppresses the growth of ectopic endometrium in vitro and in vivo, and results in a significant improvement in generalized hyperalgesia in rats with induced endometriosis. Therefore, andrographolide may be cytoreductive and may relieve pain symptoms in women with endometriosis. With excellent safety and cost profiles, andrographolide could be a promising therapeutic agent for endometriosis.

• Authors: Yu Zheng, Xishi Liu, Sun-Wei Guo
• Journal: Human reproduction (Oxford, England) (Hum Reprod) Vol. 27 Issue 5 Pg. 1300-13 (May 2012) ISSN: 1460-2350 [Electronic] England
• PMID: 22402211 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diterpenes
• NF-kappa B
• Neoplasm Proteins
• Nucleocytoplasmic Transport Proteins
• p65 oncofetal mRNA transport protein, rat
• andrographolide
• Nerve Growth Factor
• Cyclooxygenase 2
• ATPases Associated with Diverse Cellular Activities
• DNA Helicases
• Ruvbl1 protein, rat

Topics

• ATPases Associated with Diverse Cellular Activities
• Animals
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Cyclooxygenase 2 (metabolism)
• DNA Helicases (metabolism)
• Diterpenes (pharmacology, therapeutic use)
• Endometriosis (drug therapy, pathology)
• Female
• Humans
• NF-kappa B (antagonists & inhibitors, metabolism)
• Neoplasm Proteins (metabolism)
• Nerve Growth Factor (metabolism)
• Nucleocytoplasmic Transport Proteins (metabolism)
• Phosphorylation
• Rats