Berberine regulates melanin synthesis by activating PI3K/AKT, ERK and GSK3β in B16F10 melanoma cells

Song,Young  Chan; Lee,Yonghee; Kim,Hyeong  Mi; Hyun,Moo  Yeol; Lim,Yun  Young; Song,Kye  Yong; Kim,Beom  Joon

doi:10.3892/ijmm.2015.2113

Berberine regulates melanin synthesis by activating PI3K/AKT, ERK and GSK3β in B16F10 melanoma cells

Authors:
- Young Chan Song
- Yonghee Lee
- Hyeong Mi Kim
- Moo Yeol Hyun
- Yun Young Lim
- Kye Yong Song
- Beom Joon Kim
View Affiliations

Affiliations: Department of Pathology, Chung‑Ang University College of Medicine, Seoul, Republic of Korea, Department of Dermatology, Chung‑Ang University College of Medicine, Seoul, Republic of Korea
Published online on: February 26, 2015 https://doi.org/10.3892/ijmm.2015.2113
Pages: 1011-1016

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Berberine, an isoquinoline alkaloid, has a wide range of beneficial properties, including anti‑bacterial, anti‑inflammatory, anti‑cancer, and cholesterol‑lowering effects. Recently findings suggest that berberine improves glucose and lipid metabolism disorders. In the present study, we examined the mechanism underlying the inhibitory effect of berberine on α‑melanocyte‑stimulating hormone (α‑MSH)‑stimulated B16F10 melanoma cells. The results showed that berberine attenuated α‑MSH induction of the microphthalmia‑associated transcription factor (MITF) and tyrosinase in a dose‑dependent manner. To elucidate the mechanism underlying the inhibitory effect of berberine, we examined the effect of α‑MSH‑stimulated phosphorylation of PI3K/AKT, ERK, and GSK3β. The results showed that treatment with berberine resulted in a reduction in the phosphorylation of PI3K/AKT, ERK, and GSK3β. Taken together, the results suggested that berberine inhibits melanin synthesis and tyrosinase activity by downregulating the expression of MITF and tyrosinase. Thus, these findings may contribute to the potential application of berberine in the prevention and treatment of skin pigmentation disorders.

View Figures

View References

1	Buscà R and Ballotti R: Cyclic AMP a key messenger in the regulation of skin pigmentation. Pigment Cell Res. 13:60–69. 2000. View Article : Google Scholar : PubMed/NCBI
2	Costin GE and Hearing VJ: Human skin pigmentation: melanocytes modulate skin color in response to stress. FASEB J. 21:976–994. 2007. View Article : Google Scholar : PubMed/NCBI
3	Yamaguchi Y, Brenner M and Hearing VJ: The regulation of skin pigmentation. J Biol Chem. 282:27557–27561. 2007. View Article : Google Scholar : PubMed/NCBI
4	Kubo I, Kinst-Hori I, Chaudhuri SK, Kubo Y, Sánchez Y and Ogura T: Flavonols from Heterotheca inuloides: tyrosinase inhibitory activity and structural criteria. Bioorg Med Chem. 8:1749–1755. 2000. View Article : Google Scholar : PubMed/NCBI
5	Cho JC, Rho HS, Baek HS, et al: Depigmenting activity of new kojic acid derivative obtained as a side product in the synthesis of cinnamate of kojic acid. Bioorg Med Chem Lett. 22:2004–2007. 2012. View Article : Google Scholar : PubMed/NCBI
6	Ahn SM, Rho HS, Baek HS, et al: Inhibitory activity of novel kojic acid derivative containing trolox moiety on melanogenesis. Bioorg Med Chem Lett. 21:7466–7469. 2011. View Article : Google Scholar : PubMed/NCBI
7	Cabanes J, Chazarra S and Garcia-Carmona F: Kojic acid, a cosmetic skin whitening agent, is a slow-binding inhibitor of catecholase activity of tyrosinase. J Pharm Pharmacol. 46:982–985. 1994. View Article : Google Scholar : PubMed/NCBI
8	Maeda K and Fukuda M: Arbutin: mechanism of its depigmenting action in human melanocyte culture. J Pharmacol Exp Ther. 276:765–769. 1996.PubMed/NCBI
9	Parvez S, Kang M, Chung HS, et al: Survey and mechanism of skin depigmenting and lightening agents. Phytother Res. 20:921–934. 2006. View Article : Google Scholar : PubMed/NCBI
10	Nakajima M, Shinoda I, Fukuwatari Y and Hayasawa H: Arbutin increases the pigmentation of cultured human melanocytes through mechanisms other than the induction of tyrosinase activity. Pigment Cell Res. 11:12–17. 1998. View Article : Google Scholar : PubMed/NCBI
11	Wei CI, Huang TS, Fernando SY and Chung KT: Mutagenicity studies of kojic acid. Toxicol Lett. 59:213–220. 1991. View Article : Google Scholar : PubMed/NCBI
12	Giroir LE, Huff WE, Kubena LE, et al: Toxic effects of kojic acid in the diet of male broilers. Poult Sci. 70:499–503. 1991. View Article : Google Scholar : PubMed/NCBI
13	Parshad R, Sanford KK, Price FM, et al: Protective action of plant polyphenols on radiation-induced chromatid breaks in cultured human cells. Anticancer Res. 18:3263–3266. 1998.PubMed/NCBI
14	Tu CX, Lin M, Lu SS, Qi XY, Zhang RX and Zhang YY: Curcumin inhibits melanogenesis in human melanocytes. Phytother Res. 26:174–179. 2012. View Article : Google Scholar
15	al-Sereiti MR, Abu-Amer KM and Sen P: Pharmacology of rosemary (Rosmarinus officinalis Linn) and its therapeutic potentials. Indian J Exp Biol. 37:124–130. 1999.
16	Stermitz FR, Lorenz P, Tawara JN, Zenewicz LA and Lewis K: Synergy in a medicinal plant: antimicrobial action of berberine potentiated by 5′-methoxyhydnocarpin, a multidrug pump inhibitor. Proc Natl Acad Sci USA. 97:1433–1437. 2000. View Article : Google Scholar
17	Kuo CL, Chi CW and Liu TY: The anti-inflammatory potential of berberine in vitro and in vivo. Cancer Lett. 203:127–137. 2004. View Article : Google Scholar : PubMed/NCBI
18	Fukuda K, Hibiya Y, Mutoh M, Koshiji M, Akao S and Fujiwara H: Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells. J Ethnopharmacol. 66:227–233. 1999. View Article : Google Scholar : PubMed/NCBI
19	Kong W, Wei J, Abidi P, et al: Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med. 10:1344–1351. 2004. View Article : Google Scholar : PubMed/NCBI
20	Yang J, Yin J, Gao H, Xu L, Wang Y and Li M: Berberine improves insulin sensitivity by inhibiting fat store and adjusting adipokines profile in human preadipocytes and metabolic syndrome patients. Evid Based Complement Alternat Med. 2012:3638452012.PubMed/NCBI
21	Chen Y, Wang Y, Zhang J, Sun C and Lopez A: Berberine improves glucose homeostasis in streptozotocin-induced diabetic rats in association with multiple factors of insulin resistance. ISRN Endocrinol. 2011:5193712011. View Article : Google Scholar
22	Hamsa TP and Kuttan G: Antiangiogenic activity of berberine is mediated through the downregulation of hypoxia-inducible factor-1, VEGF, and proinflammatory mediators. Drug Chem Toxicol. 35:57–70. 2012. View Article : Google Scholar
23	Santini E, Valjent E, Usiello A, et al: Critical involvement of cAMP/DARPP-32 and extracellular signal-regulated protein kinase signaling in L-DOPA-induced dyskinesia. J Neurosci. 27:6995–7005. 2007. View Article : Google Scholar : PubMed/NCBI
24	Wang JL, Chan RC, Cheng HH, et al: Short waves-induced enhancement of proliferation of human chondrocytes: involvement of extracellular signal-regulated map-kinase (erk). Clin Exp Pharmacol Physiol. 34:581–585. 2007. View Article : Google Scholar : PubMed/NCBI
25	Yoon HS, Lee SR, Ko HC, et al: Involvement of extracellular signal-regulated kinase in nobiletin-induced melanogenesis in murine B16/F10 melanoma cells. Biosci Biotechnol Biochem. 71:1781–1784. 2007. View Article : Google Scholar : PubMed/NCBI
26	Li H and Min YS: Inhibition of melanogenesis by Xanthium strumarium L. Biosci Biotechnol Biochem. 76:767–771. 2012. View Article : Google Scholar : PubMed/NCBI