Beneficial biological effects of Flavokawain A, a chalcone constituent from kava, on surgically induced endometriosis rat model

Abstract

Ethnopharmacological relevance: Shrub kava has long been grown and utilized, primarily in the South Pacific region, for ceremonial, religious, and social occasions. It has been used as a pain reliever and muscle relaxant in medicinal practices from the eighteenth century. Interestingly, relatively low incidence of lung cancer may attribute to the high consumption of kava products in this region.

Aim of the study: Kava extracts were used to produce the kava chalcones Flavokawain A, B and C, which have a variety of bioactivities. In the present study, we show that Flavokawain A has positive effects on endometriosis.

Materials and methods: The endometriosis rat model was surgically induced by the autologous transplantation of endometrial tissue. Rats were evaluated for clinical ratings and lesion volume following a 6-week Flavokawain A therapy. Peritoneal fluid and blood samples were taken and ELISA assay was used to measure the cytokines and chemokines levels. Transcriptional and expression levels of Akt, PI3K, NF-kB, iNOS, Bcl-2, Bax and caspase-3 were evaluated by Western blotting and RT-qPCR. Implanted tissue sections of the rats were also analyzed by immunofluorescent and histopathological staining.

Results: Lesion volumes and adhesion scores were successfully decreased. Blood and peritoneal fluid levels of associated cytokines and chemokines were markedly down-regulated. Besides, Flavokawain A also mediated cell apoptosis of endometrial implants. Additionally, VEGF expression was reduced, which inhibited the angiogenesis process. As for the expression of Akt, p-Akt, PI3K, p-PI3K, and NF-kB in endometriosis lesions, Flavokawain A significantly reduced them.

Conclusion: Flavokawain A has beneficial effects on the surgically induced endometriosis rat model, by reducing inflammation, promoting apoptosis, and decreasing angiogenesis. Our findings suggest that these effects may be mediated through the regulation of PI3K/Akt and NF-κB signaling pathways.

Keywords: Angiogenesis; Apoptosis; Chalcones; Endometriosis; Flavokawain A; Inflammation.