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

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.

Berberine exerts an anti-inflammatory role in ocular Behcet's disease

“…Aside from its traditional use as a treatment for gastrointestinal disorders, BBR has been demonstrated to exhibit inhibitory functions in a number of additional diseases, including cancer (2), microbial infection (3), inflammatory and autoimmune diseases (such as cardiovascular disease) (4), collagen-induced arthritis (5), experimental type I diabetes in mice (6) and experimental autoimmune encephalomyelitis (EAE) (7). Numerous reports have demonstrated that BBR may suppress the Th17 response in certain autoimmune diseases (6–8).…”

An Update On Natural Compounds and Their Modern Formulations for the Management of Malignant Melanoma

“…While best known for antimicrobial, antiinflammatory, anti-hyperglycemic, and anti-hyperlipidemic effects [131], berberine is one of the most active alkaloids in melanoma. It has been shown to inhibit kinases like PI3K, ERK, and GSK3β [132]. Moreover, in combination with doxorubicin, it intensely reduces proliferation and increases apoptosis, effect demonstrated both in vitro and in vivo [133].…”

Chronic over-nutrition and dysregulation of GSK3 in diseases

“…Nutrients that affect PI3K/Akt pathway include water, proteins, carbohydrates, and fats (Table 2 ). Hypo-osmotic [ 46 – 48 ] or hyper-osmotic stresses [ 49 – 52 ] associated with disorders in water homeostasis are known to involve the PI3K/Akt signaling. Non-denatured and denatured proteins can activate PI3K/Akt.…”

“… Despite inducing the p21-activated serine-threonine kinase, requiring PI3K activation, within 30-min, hyper-osmotic stress suppresses melanin production that also requires PI3K activation, for days of the treatment, suggesting overstimulation of the PI3K/Akt pathway. [ 5 , 49 – 52 ] Proteins Non-denatured protein Male SD rats, human embryonic kidney cells. Branched-chain amino acids in cow milk are highly insulinotropic and a potent activator of PI3K/Akt.…”

“… High salt foods (mainly NaCl) cause potential hyperosmotic stress, which modulates PI3K/Akt/GSK3 activities; increase or decrease phosphorylation of NaCl transporter, regulated via insulin/PI3K pathway by low salt diet or high salt diet; high salt food causes early insulin resistance, stage 0 of the kinase insensitivity (Table 1 ). [ 24 , 49 – 52 , 108 , 109 ] Calcium Mouse osteoblast, human thyroid cancer cells, mouse neural crest cells. Exert effects on PI3K/Akt and/or GSK3 pathway.…”