The JAK2/STAT3 pathway is involved in the anti-melanoma effects of atractylenolide I.

In this study, we aimed to investigate the anti-melanoma effects and the JAK2/STAT3 pathway-related mechanism of action of atractylenolide I in human melanoma cells. Our results showed that atractylenolide I effectively reduced viability, induced apoptosis and inhibited migration of melanoma cells. Meanwhile, atractylenolide I decreased the protein expression levels of phospho-JAK2 and phospho-STAT3, and in turn downregulated the mRNA levels of STAT3-targeted genes, including Bcl-xL, MMP-2 and MMP-9. Furthermore, the cytotoxic effect of atractylenolide I was attenuated in STAT3-overactivated A375 cells. These findings indicate that inhibition of JAK2/STAT3 signalling contributes to the anti-melanoma effects of atractylenolide I.

Inhibiting STAT3 signaling is involved in the anti-melanoma effects of a herbal formula comprising Sophorae Flos and Lonicerae Japonicae Flos.

A herbal formula (SL) comprising Sophorae Flos and Lonicerae Japonicae Flos was traditionally used to treat melanoma. Constitutively active signal transducer and activator of transcription 3 (STAT3) has been proposed as a therapeutic target in melanoma. Here we investigated whether an ethanolic extract of SL (SLE) exerted anti-melanoma activities by inhibiting STAT3 signaling. B16F10 allograft model, A375 and B16F10 cells were employed to assess the in vivo and in vitro anti-melanoma activities of SLE. A375 cells stably expressing STAT3C, a constitutively active STAT3 mutant, were used to determine the role of STAT3 signaling in SLE's anti-melanoma effects. Intragastric administration of SLE (1.2 g/kg) potently inhibited melanoma growth in mice and inhibited STAT3 phosphorylation in the tumors. In cultured cells, SLE dramatically reduced cell viability, induced apoptosis, suppressed migration and invasion, and restrained STAT3 activation and nuclear localization. STAT3C overexpression in A375 cells diminished SLE's effects on cell viability, apoptosis and invasion. Collectively, SLE exerted potent anti-melanoma effects partially by inhibiting STAT3 signaling. This study provides pharmacological justification for the traditional use of this formula in treating melanoma, and suggests that SLE has the potential to be developed as a modern alternative and/or complimentary agent for melanoma treatment and prevention.

Danshen prevents the occurrence of oxidative stress in the eye and aorta of diabetic rats without affecting the hyperglycemic state.

Oxidative stress has been implicated in the pathogenesis of diabetic complications. We have previously demonstrated the occurrence of oxidative stress in the eye and aorta but not in the kidney of diabetic rats. In the present study we have investigated the effects of danshen, a herb used in traditional Chinese medicine to treat ailments related to diabetic complications, on the onset of oxidative stress in the above tissues. Diabetic rats were treated with 3 g/kg of danshen via oral intubation for 7 weeks. Afterwards, the tissue levels of glutathione (GSH), the primary endogenous antioxidant, and malondialdehyde (MDA), a marker of oxidative stress, were measured. Our results showed that danshen treatment did not alter the hyperglycemic status of the diabetic animals. However, the GSH levels were normalized in both the eye and aorta of the diabetic rats when these rats were administered with danshen. Administration with danshen also restored the level of MDA in the eye and aorta of the diabetic rats to that found in the control rats. These changes, however, were not observed in the kidney where oxidative stress did not occur. These results suggested that oral administration of danshen can effectively prevent the occurrence of oxidative stress in the eye and aorta of the diabetic rats. Furthermore, danshen treatment did not affect the blood glucose concentration of the animals irrespective of their diabetic state. These data therefore provide important information on mode of action of danshen, thereby establishing a basis for this herb to be used as a supportive treatment regime to ameliorate the severity of diabetic complications.

Alterations in antioxidant enzyme activities in the eyes, aorta and kidneys of diabetic rats relevant to the onset of oxidative stress.

Profound changes in antioxidant enzyme activities were observed in a number of vascular tissues during the development of streptozotocin-induced diabetes in rats. In the eyes, there was an increase in superoxide dismutase activity at week 4 of diabetes. However, no difference in superoxide dismutase activity was observed between the control and diabetic animals at week 8. On the other hand, the diabetic state did not seem to affect the catalase activity in the eyes. There was a generalized increase in catalase activity of the eyes from week 4 to week 8 irrespective of the diabetic state. For glutathione peroxidase in the eyes, a decreased activity was observed in the diabetic animals at week 8, but not in week 4. A different pattern of enzyme activity changes was observed in the aorta where an increase in superoxide dismutase activity was observed in the diabetic group at week 4 but not in week 8. On the other hand, an increase in catalase activity was observed only at week 8 but not at week 4. Whereas there was no observed difference between the control and diabetic animals in glutathione peroxidase activity in the aorta, except for a generalized decrease from week 4 to week 8 in both groups of animals. In big contrast to the eyes and aorta where an increase in superoxide dismutase activity was observed at week 4 of diabetes, no change in kidney superoxide dismutase activity was noted at week 4 and a decrease was observed at week 8. A similar pattern of enzyme activity changes was observed for glutathione peroxidase in the kidneys. The catalase activity in the kidneys was not affected at all by the diabetic state at both week 4 and week 8. These results clearly demonstrate the active involvement of these antioxidant enzymes during the development of diabetes, and could be rationalized by the differential response of the tissues towards the different extent of oxidative stress imposed by the diabetic state on the different tissues.