Viaminate Inhibits Propionibacterium Acnes-induced Abnormal Proliferation and Keratinization of HaCat Cells by Regulating the S100A8/S100A9- MAPK Cascade.

BACKGROUND: Viaminate, a vitamin A acid drug developed in China, has been clinically used in acne treatment to regulate epithelial cell differentiation and proliferation, inhibit keratinization, reduce sebum secretion, and control immunological and anti-inflammatory actions; however, the exact method by which it works is unknown. METHODS: In the present study, acne was induced in the ears of rats using Propionibacterium acnes combined with sebum application. RESULTS: After 30 days of treatment with viaminate, the symptoms of epidermal thickening and keratin overproduction in the ears of rats were significantly improved. Transcriptomic analysis of rat skin tissues suggested that viaminate significantly regulated the biological pathways of cellular keratinization. Gene differential analysis revealed that the S100A8 and S100A9 genes were significantly downregulated after viaminate treatment. The results of qPCR and Western blotting confirmed that viaminate inhibited the expression of S100A8 and S100A9 genes and proteins in rat and HaCat cell acne models, while its downstream pathway MAPK (MAPK p38/JNK/ERK1/2) protein expression levels were suppressed. Additional administration of the S100A8 and S100A9 complex protein significantly reversed the inhibitory effect of viaminate on abnormal proliferation and keratinization levels in acne cell models. CONCLUSION: In summary, viaminate can improve acne by modulating S100A8 and S100A9 to inhibit MAPK pathway activation and inhibit keratinocyte proliferation and keratinization levels.

Viaminate ameliorates Propionibacterium acnes-induced acne via inhibition of the TLR2/NF-κB and MAPK pathways in rats.

Viaminate, a retinoic acid derivative developed in China, has been clinically used for acne treatment to regulate and control keratinocyte cell differentiation and proliferation, inhibit keratinization, reduce sebum secretion, and regulate immune and anti-inflammatory functions; however, its potential molecular mechanism has not yet been elucidated. Therefore, we induced ear acne in rats using Propionibacterium acnes and sebum application. Symptoms of ear redness, epidermal thickening, inflammatory reaction, keratin overproduction, subcutaneous oil, and triglyceride (TG) accumulation improved significantly in acne model rats treated with viaminate for 30 days. Transcriptome analysis of rat skin tissues suggested that viaminate had significant regulatory effects on fatty acid metabolism and cellular keratinization pathways. Molecular target prediction suggested that toll-like receptor 2 (TLR2) may be a key target of viaminate's therapeutic mechanism. Western blotting results confirmed that viaminate inhibited the TLR2 and its downstream pathways, nuclear factor-kappa B (NF-κB) [NF-κB inhibitor alpha (IκBα)/NF-κB-p65] and mitogen-activated protein kinases (MAPKs) [MAPK p38/c-Jun N-terminal kinase (JNK)/extracellular regulated kinase 1/2 (ERK1/2)] in acne vulgaris rats. In vitro studies revealed that viaminate treatment attenuated P. acnes proliferation and P. acnes-induced inflammatory response in human keratinocytes and has an inhibitory effect on the activation of NF-κB and MAPKs, while overexpression of TLR2 attenuated these effects. In conclusion, viaminate ameliorates P. acnes-induced acne by inhibiting the proliferation and inflammatory response of keratinocytes, ascribed to the deactivation of the TLR2-mediated NF-κB and MAPK pathways.

Feasibility Study for the Long-Term Management of Refractory Hyperkeratotic Eczema with Calcipotriol and Betamethasone Dipropionate (Daivobet®), Viaminate and Concomitant Conventional Therapies: A Retrospective Study.

BACKGROUND: The available treatments for refractory hyperkeratotic eczema are inadequate with frustrating results. We, therefore, incorporated Calcipotriol and Betamethasone Dipropionate (Daivobet®), and Viaminate into the mainstay treatment to improve the clinical symptoms. The study aimed to evaluate the efficacy of Daivobet ® and Viaminate as a potential treatment alternative for refractory hyperkeratotic eczema. PATIENTS AND METHODS: Between 2013 and 2015, 61 patients diagnosed with refractory hyperkeratotic eczema (RHE) who had shown inadequate response to conventional therapies were pooled from a single center. Besides, they were all treated with Daivobet ® , Viaminate, and an occlusive dressing mixture containing 5% salicylic acid ointment and 25% zinc oxide paste following inadequate response to conventional therapies (corticosteroids plus 25% zinc oxide paste and 5% salicylic acid ointment). Investigators Global Assessment (IGA) and Patient-Oriented Eczema Measure (POEM) assessed baseline and outcome measures for the degree of hyperkeratinization (0-clear; 3-moderate; 4-severe). RESULTS: Of the 61 patients, 49 (80.3%) patients presented with moderate RHE and 12 (19.7%) with severe RHE. After 24 weeks of treatment, the period for loss of keratinization was significantly lower in patients with moderate RHE (3.9±1.9 weeks) than those with severe RHE (10.8±1.0 weeks) with a P-value <0.01. Furthermore, they required a significantly shorter total treatment duration (10.6 ± 4.3 weeks) than those with severe RHE (20.3±3.6 weeks) with a P-value of <0.01. However, there were no significant differences in post hoc analysis at week 36 with P-values of 0.46 and 1.00 for IGA and POEM, respectively. CONCLUSION: Our results showed that the incorporation of Viaminate and Daivobet® into mainstay treatment was effective and safe for the long-term management of RHE.

Fatal Hepatotoxicity Due to Viaminate.

Viaminate is a derivative of retinoic acid (tretinoin) used in the treatment of severe acne and other disorders of keratinization. Liver dysfunction due to viaminate therapy has not been well described and there have been no reported deaths due to viaminate-induced hepatotoxicity. Herein, we report the case of a woman who underwent treatment at the hospital for 38 days and died of hepatic failure after taking viaminate for more than 2 months. This case provides further insight into viaminate-induced hepatotoxicity.

The safety and feasibility analysis of viaminate capsule in the treatment of seborrheic dermatitis / 中国基层医药

Objective To investigate the safety and feasibility of viaminate capsule in the treatment of sebor-rheic dermatitis.Methods According to the digital table, 84 patients with seborrheic dermatitis were randomly divided into the observation group(n=42) and the control group(n=42).The control group were treated with 1%pimecrolimus cream coated, 2 times/d.The observation group were treated with capsule viaminate, 50mg/times, 2 times/d,2 weeks for a course of treatment.The clinical efficacy of the two groups were observed.Results The ery thema,scaling,seborrhea,itching and other symptoms score and total score after treatment to 4 weeks,8 weeks of the two groups were compared(Erythema t=5.865,5.786;scaly t=6.112,5.886;seborrhea t=5.963,5.629;itching t=6.123,6.072.all P0.05).Conclusion Viaminate cap-sule can improve in a short period of time in patients with clinical symptoms of seborrheic dermatitis,the effect is sig-nificant,the recurrence rate is low,safe and effective.

Effect of itraconazole on pharmacokinetics of viaminate in healthy subjects / 中国药理学通报

Aim To investigate the effect of oral itraconazole on pharmacokinetics of viaminate and under-stand the metabolism pathway of viaminate in healthy humans,as well as guide the reasonable medication for viaminate and itraconazole coadministration.Methods The study was conducted in a double-blind randomized and crossover manner with two phases of treatment with placebo-viaminate or itraconazole-viaminate.Eight healthy male subjects received an oral dose of 200 mg itraconazole(QD) or matched placebo for five consecutive days,and took an oral 100 mg dose of viaminate on day 4 after each treatment phase.The liquid chromatography-mass spectrometry(LC-MS) was established to measure the blood drug concentration of viaminate.Results Our results showed that the mean peak concentration of viaminate was increased with itraconazole [(21.21?11.65) ?g?L~(-1) vs(27.12?13.83) ?g?L~(-1),P0.05].Additionally,the mean elimination half life was prolonged [(2.71?0.38) h vs(4.43?0.93) h,P

Comparison of isotretinoin and viaminate in the treatment of moderate to severe acne vulgaris:a multiple-centre,randomized,double-blind,comparative clinical trial / 中华皮肤科杂志

Objective To evaluate the efficacy and safety of isotretinoin and viaminate for the treatment of moderate to severe acne vulgaris.Methods A multiple-centre,double-blind,double-analog comparative clinical trial was conducted.Patients diagnosed with moderate to severe acne by GAGS (global acne grading system) were randomly divided into isotretinoin group (10 mg,bid) and viaminate group (50 mg,tid);treatment was done for a total of 6 weeks.All subjects were evaluated before treatment,and at 2,4,6 weeks after the initiation of treatment,for evaluation of lesion count,and for observation of thera- peutic effects and side effects.Results A total of 217 patients were enrolled this trial,of which,213 could be evaluated in a FAS (Full Analysis Set) analysis and 200 in a PPS (per protocol) analysis.There was no significant difference in the efficacy at 2,4,6 weeks after the initiation of treatment between the isotretinoin group and viaminate group (6.0% vs 5.0%,29.0% vs 20.0%,57.0 % vs 51.0 %,respectively). However,the inflammatory papules and pustules decreased more rapidly in the isotretinoin group than in the viaminate group at each of the follow up evaluations (all P＜0.05).There was no obvious difference in the rate of clearance of comedones and nodules between the two groups.Both the occurrence rate (68.81% vs 36.53%,P＜0.001) and severity (P＜0.05) of side effects were higher in the isotretinoin group than in the viaminate group.The main adverse events included mouth dryness,dizziness,etc,occurred more fre- quently in the isotretinoin group than in the viaminate group.Conclusion For the treatment of moderate to severe acne,the efficacy of isotretinoin is similar to that of viaminate;however,isotretinoin has more imme- diate effect with more side effects than viaminate.