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วนัชวรรณ วิสุทธิพรต
Neti Waranuch
เนติ วระนุช
Naresuan University. Faculty of Pharmaceutical Sciences
Keywords: Acanthus ebracteatus
androgenic alopecia
Issue Date: 2022
Publisher: Naresuan University
Abstract: Androgenic alopecia (AGA) is a serious skin disorder that leads to baldness. Testosterone metabolism catalyzed by 5α-reductase results in dihydrotestosterone (DHT) production which triggers a chain reaction of the release of proteins that cause hair follicle damage, which induces hair follicle inflammation which, in turn, results in apoptosis of dermal papilla cells resulting in a reduction in the quantity of those cells. Miniaturization of the hair follicles, resulting from the decrease in the number of dermal papilla cell number makes the balding scalp evident. Topical minoxidil and oral finasteride are approved medications for the treatment of hair loss. However, these synthetic substances sometimes manifest undesirable adverse effects such as itching, skin rash, loss of erectile function and libido, etc. Therefore, many medicinal plants, used as traditional remedies, have been investigated for anti-hair loss activity. The objective of our study was to develop an anti-hair loss application containing extract from Acanthus ebracteatus Vahl. (AE) which contains a prominent verbascoside (VB). The development process was the evaluation of AE bioactivity associated with the pathogenesis of the AGA pathway. VB stability was evaluated by using Arrhenius’ theory and shelf-life was then obtained. SLN loaded AE extract was developed for improving VB limitations. Finally, the application of the AE extract containing VB was evaluated for its safety and effectiveness with participating volunteers. Regarding AE extract standardization, ethanolic extract showed the highest content of VB and did not present a cytotoxic effect on dermal papilla cells. It did, however, induce dermal papilla cell proliferation which occurred with AE extract 250 µg/mL and VB 62.50 µg/mL. The number of G2/M and S phases increased within 24 hours of treatment. As well, both AE extract and VB showed a preventative effect on the dermal papilla cell apoptosis by decreasing the number of cells in the G1 phase. The anti-androgenic activity was demonstrated by the inhibition of 5α-reductase and prevention of testosterone induced dermal papilla cell apoptosis. The ethanolic extract of AE showed the IC50 value of the inhibition of 5α-reductase activity at 60.45 µg/mL while VB did not show any inhibition activity. Interestingly, both AE extract and VB showed the preventive effect on dermal papilla cell apoptosis caused by 200 µM testosterone. In addition, 125 – 250 µg/mL AE extract and 64.25 µg/mL VB was effective in inhibiting the release of pro-inflammatory cytokines. IL-1β, TNF-α, and nitric oxide were released from the RAW 267.4 cells, induced by the LPS. Also, IL-1α and IL-6 were released from UV irradiated dermal papilla cells. VB is a glycoside that is easily degraded when kept at a high temperature or dissolved in an alkaline solution. According to Arrhenius’ theory, the result indicated a first-order reaction of VB degradation. Arrhenius’ theory indicated an estimated shelf-life of VB in AE extract (semi-solid form) of 75 days and the estimated shelf-life of the AE extract in solution form of 12 days. However, our results indicated the real-time shelf-life of VB in solution form as 35 days, significantly longer than the estimated shelf-life. VB in AE extract was encapsulated in SLN for improving the stability of VB and enhancing skin permeation. Compritol® ATO 888 (0.1%) was used as the lipid carrier and the particles formed and stabilized by using 0.50% Tween 80 and 3.0% Span 80. The optimized condition produced SLN with 32% entrapment efficiency and particle size of approximately 600 nm. The shelf life of SLN containing the AE extract was 172 days. Clearly, the SLN increased the VB stability significantly. The VB encapsulated in SLN also showed sustained release in both in vitro release and skin permeation studies. SLN loaded AE extract incorporated in the hydrogel was the subject of further study in a clinical trial for evaluating the product safety and effectiveness. The result indicated that SLN loaded AE extract, including hydrogel base, showed non-skin irritation in 20 participating volunteers. Seventy-two volunteers were allocated into 4 groups for evaluation of the effectiveness of hair serum and test products. Three of the groups were treated with a product that contained either minoxidil, or a hair serum containing SLN loaded AE extract, or a combined treatment (minoxidil + hair serum), while the fourth, control, group was administered a placebo. The results showed that the hair serum containing SLN loaded AE extract increased the number of hairs within 3 months as did both the combined treatment and the minoxidil. Anagen hair was significantly increased from baseline when the hair serum and the combined treatment were applied for 1 month while the minoxidil was significant at the 5th month. In all, the effectiveness of the hair serum in increasing the number of anagen hairs was significantly greater than that of the placebo. The effect of hair serum on anagen hair was not significantly different from the effectiveness of minoxidil. The effect of the hair serum, the combined treatment and the minoxidil on the increase of anagen hair density correlated with the effect on telogen hair that was significantly decreased from the baseline. In addition to the effect on hair numbers, the hair serum increased hair strength, as indicated by the decrease in hair fall in the hair comb test. No volunteer showed any adverse effect from the hair serum during the clinical study period. Our study evaluated the bioactivities of AE extract including the evaluation of safety and the efficacy of hair serum containing AE extract. The results of in vitro testing indicates that AE extract containing VB is a promising ingredient for developing hair growth-promoting products. Furthermore, clinical data showed no adverse effects or reactions from the hair serum in volunteers with MPHL, thereby indicating that it can be safely used as a medicinal treatment for hair growth in AGA patients.
Description: Doctor of Philosophy (Ph.D.)
ปรัชญาดุษฎีบัณฑิต (ปร.ด.)
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