A Randomised Controlled Trial: The effect of oral astaxanthin as an anti-inflammatory agent on serum level of e-selectin in acne vulgaris

Background: E-selectin plays a pivotal role in the inflammatory response of acne. Astaxanthin (AST), an supplement claimed having anti-inflammatory and antioxidant properties, has potential in inflammatory skin therapy. This study aims to determine the effect of oral AST as an anti-inflammatory agent on the serum level of e-selectin in acne vulgaris. Methods: This is a double-blind, randomized controlled trial study with a pretest and posttest control group design. The participants were 34 acne vulgaris patients with inflammatory lesions (papulopustular acne). The participants are randomly assigned to the treatment or control group to receive oral tablet of 4 mg of AST or placebo in addition to standard acne therapy of tretinoin cream 0.025% and clindamycin cream 1.2%. Each group was measured for the serum level of E-selectin before therapy (pretest) and after one month of therapy (posttest). Results: The pretest and posttest level of the mean serum e-selectin in the treatment group were 50.21 ± 21.12 ng/ml and 50.04 ± 22.99 ng/ ml, respectively. There is no significant difference between the pretest and posttest of the mean e-selectin level in the treatment group (p=0.943). While, the pretest and posttest of mean serum e-selectin level in control group were 57.84 ± 20.71 ng/ml and 55.87 ± 15.98 ng/ml, respectively. There is no significant difference between the pretest and posttest of the mean e-selectin level in the control group (p=0.453). There was a decrease in the mean serum e-selectin level of the treatment and control groups one month after therapy. However, the decrease of the mean e-selectin level between treatment and control group is not significantly different (p=0.547). Conclusion: The addition of oral AST to standard acne therapy shows no significant difference in reducing the serum e-selectin level compared to placebo.


INTRODUCTION
Acne vulgaris (AV) is a chronic multifactorial disorder of the pilosebaceous unit which occurs as a result of an interaction between the release of inflammatory mediators, follicular hyperkeratinization with subsequent plugging of the follicle, Propionibacterium acnes (P.][5] In normal condition, the inflammation provide protection against infections and tissue damages through vasodilation and recruitment of immune cells and plasma proteins.However, the dysregulated inflammatory response can cause excessive or prolonged tissue damage, which plays a role in the development of acute or chronic inflammatory diseases.In the chronic inflammation, the nuclear factor-kappa beta (NF-κB) induces pro-inflammatory genes, innate and adaptive immune cells. 6he aberration in NF-κB activity is associated with various inflammatory diseases.This process is targeted by anti-inflammatory drugs to suppress the expression of inflammatory cytokines. 7A similar response of NF-κB activation is found in acne lesion. 8he NF-κB activation is associated with inflammatory cytokines production.Inflammatory cytokines induce the expression of cell adhesion molecules. 9These molecules can be found in the surface of endothelial cells surface, such as e-selectin, intercellular cell adhesion molecules (ICAM)-1, and vascular cell adhesion molecules (VCAM)-1.They mediate the adhesion and extravasation of leukocytes.In response to pro-inflammatory cytokines, interleukin (IL)-1β and tumor necrosis factor (TNF)-α, endothelial cells express e-selectin. 10NF-κB pathway activation triggers the upregulation of the expression of the e-selectin, ICAM-1, and VCAM-1 in response to various inflammatory cytokines. 11Then, e-selectin is synthesized and expressed on the endothelial cell surface within 1 to 2 hours in response to IL-1 and

ORIGINAL ARTICLE
TNF. 12 Hence, e-selectin expression was elevated in acne lesions. 13 This agent prevents inflammatory processes by blocking pro-inflammatory genes expression as a consequence of suppressing NF-κB activation. 16AST can be an exciting new strategy for treating inflammatory skin diseases. 17his study aimed to investigate the effect of oral astaxanthin as an anti-inflammatory agent on serum e-selectin level in acne vulgaris.

METHODS
This research was a double-blind randomized control trial with a pre-and post-test control group design.This research is approved by the RSUD Dr Moewardi Ethical Committee (Ethical Clearance No.1.138/X/HREC/2019).The written informed consent was obtained from the participants before the research is conducted.The participants were acne vulgaris patients of RSUD Dr Moewardi outpatient clinic from October to November 2019.The exclusion criteria were acne vulgaris patients with other inflammatory diseases, obesity, smoking, or patients were taking medications such as benzodiazepines, lithium, cyclosporine, ramipril, isoniazid, iodides, bromides, vitamin B-type complexes, serotonin uptake inhibitors, epidermal growth receptor inhibitors, progestin contraceptives, corticosteroids and anti-acne.The participants were randomly allocated into two equally numbered groups.Both groups received topical acne standard therapy of tretinoin cream 0.025% and clindamycin cream 1.2%.The cream was aplied at night.The treatment group receive an additional oral therapy of 4 mg of AST, while the control group receive an AST-similar-looking-placebo containing 4 mg of lactulose.Neither the researcher nor the subject knew whether the subject was receiving the treatment or a placebo.The serum level of e-selectin was measured before (pretest) and after a month after (posttest) therapy.The serum levels of e-selectin were determined by ELISA using a standard kit (Human sE-selectin Quantikine ELISA Kit, R&D Systems, Minneapolis, USA).The data was analysed using SPSS software version 21.0.The data distribution was determined using the Saphiro-Wilk test.The data was analysed according to intention-to-treat principle.The comparison of data within-and betweengroup was done using paired t-test and student t-test, respectively.If the data distribution is not normal, the Wilcoxon and Mann-Whitney U test will be used for analysis.

RESULTS
A total of thirty-four acne vulgaris patients (15 males and 19 females with an age range of 14-36 years) were recruited (Table 1).The pretest and posttest level of the mean serum e-selectin in the treatment group were 50.21 ± 21.12 ng/ml and 50.04 ± 22.99 ng/ ml, respectively.There is no significant difference between the pretest and posttest of the mean e-selectin level in the treatment group (p=0.943).While, the pretest and posttest of mean serum e-selectin level in control group were 57.84 ± 20.71 ng/ml and 55.87 ± 15.98 ng/ml, respectively.There is no significant difference between the pretest and posttest of the mean e-selectin level in the control group (p=0.453).There is a decrease in the mean serum e-selectin level of the treatment and control groups one month after therapy.However, the decrease of the mean e-selectin level between treatment and control group is not significantly different (p=0.547).

DISCUSSION
AST is an agent claimed with anti-inflammatory and antioxidant properties. 14AST suppresses NF-κB activation.It prevents inflammatory processes by blocking pro-inflammatory genes expression as a consequence of suppressing NF-κB activation. 16ST inhibits expression of e-selectin, ICAM-1 and VCAM-1 leading to inhibition of inflammatory cell infiltration. 18n this study, the addition of AST as an anti-inflammatory to standard acne therapy has shown no Published by DiscoverSys | Bali Med J 2020; 9(1): 41-43 | doi: 10.15562/bmj.v9i1.1674