New Spotlight: Salvianolic Acid B Reduces Oxidative Stress to Promote Hair-Growth in Mice, Human Hair Follicles and Dermal Papilla Cells.
Inhibition of Oxidative Stress Pathways Promote Hair Growth.
Introduction
Androgenetic alopecia (AGA) is a genetic condition that affects areas of the scalp. Also known as pattern hair loss, males present with thinning hair in temporal areas that proceeds to the crown (male pattern baldness) and females usually have more diffuse thinning in the crown region. There is also a reduction in hair diameter and a higher proportion of single hair follicles.
The hair growth cycle occurs in three phases, anagen, catagen and telogen. Anagen is the growth phase and telogen the resting phase with catagen the transition between the two. In AGA certain androgens such as dihydrotestosterone have been demonstrated to reduce the duration of the anagen phase, causing thinner hair and smaller hair follicles, resulting in loss of hair. Another mechanism of hair loss occurs through perifollicular fibrosis and vascular changes that perturb blood flow to the hair follicles. Dermal papilla cells are highly sensitive to these changes especially oxidative stress, which causes apoptosis, tissue hypoxia and ischemia resulting in hair follicle miniaturisation and premature aging.
Currently, finasteride and minoxidil are the FDA-approved drugs for the treatment of AGA. Finasteride blocks the conversion of testosterone to DHT and minoxidil stimulates potassium channels resulting in enhanced blood flow around the hair follicles. Both dugs delay progression of AGA but cannot cure it and may have varying degrees of side effects.
In several studies, Shikonin steroidal acid B (SAB) has been shown to have anti-oxidative, anti-inflammatory, autophagy-promoting, anti-fibrotic, and angiogenesis-promoting functions. The potential role of SAB as a novel treatment for AGA was explored in this study.
Main Points
- Depilated mice treated with SAB regained hair quicker than control treated mice. A significant promotion of hair growth was noted at day 10.
- At day 21, hair length was measured and SAB treated mice had significantly longer hair than controls.
- After 21 days SAB treatment also resulted in more blood capillaries compared to controls, indicating an increased vascularisation.
- Human hair grew longer in culture in SAB treated hairs compared to controls. The number of hairs in anagen phase was also increased with SAB treatment, 47% compared to 33% in controls.
- In dermal papilla cell cultures concentrations of SAB up to 50mg/ml increased proliferation. However. concentrations over 100mg/ml became cytotoxic.
- In a model of hydrogen peroxide induced oxidative damage, SAB significantly lowered reactive oxygen species in hair follicles. Further analysis using dermal papilla cells demonstrated reduced staining of 2′,7′-Dichlorodihydrofluorescein diacetate (DCFH-DA), a reactive oxygen species detector, indicative of SAB protection from intracellular ROS increase.
- Gene expression analysis revealed that SAB downregulated Rac1 expression in dermal papilla cells, inhibiting the assembly and activation of the NADPH oxidase system, a major component of ROS production. SAB treatment also downregulated superoxide dismutase expression indicative of reduced ROS production and better oxidative stress levels.
- Western blotting revealed downregulation of the oxidative stress marker 3-nitrotyrosine (3-NT).
- In dermal papilla cells, SAB downregulated caspase-3 expression consistent with inhibition of oxidative stress-mediated apoptosis.
- SAB significantly reduced phospho-ERK and phospho-p38 in dermal papilla cells, which is the likely mechanism of protection from oxidative damage.
Conclusion
Oxidative stress and inflammatory responses have been implicated in hair loss. SAB has been shown in other studies to have anti-oxidative and anti-inflammatory properties; however it has not been studied in hair. This study used C57BL/6 mouse models, ex vivo human hair follicle cultures, and gene expression analyses to examine SAB’s effects on hair growth. SAB promoted hair growth and the most likely mechanism of action was by down-regulating oxidative stress related genes and pathways. This study demonstrated a potential use of SAB for the treatment of AGA.
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