Greener route to acne-care ingredients shows why more antioxidants do not always make a better product

Published 29 September, 2026

A greener extraction method can concentrate antioxidant compounds from medicinal plants, but the more highly enriched fraction may not necessarily be the safest or most practical ingredient for skincare products, according to a study published in the Journal of Dermatologic Science and Cosmetic Technology.

The researchers investigated a blend of four plants used in East Asian medicine and cosmetics: Houttuynia cordata, Scutellaria baicalensis, Chamaecyparis obtusa and Artemisia capillaris. They compared the crude herbal extract with fractions produced using an ethanol–ammonium sulphate aqueous two-phase system (ATPS), a liquid-separation method designed to reduce reliance on conventional organic solvents.

ATPS selectively concentrated phenolic and flavonoid compounds while reducing triterpenes. The best-performing fraction contained 690.8 milligrams of gallic acid equivalents and 42.6 milligrams of quercetin equivalents per gram. It also recorded substantially stronger free-radical scavenging activity than the crude extract, with a DPPH IC50 of 10.67 micrograms per millilitre compared with 50.18.

Biological tests, however, revealed in zebrafish larvae the crude extract was tolerated at higher concentrations and provided stronger protection against hydrogen peroxide-induced oxidative stress. Notably, at 50 micrograms per millilitre, it increased expression of the antioxidant-related gene prdx1 by approximately 1.44-fold, while leaving gstp1 expression broadly unchanged.

Based on this safety profile, the researchers used the crude extract to formulate a foaming cleanser and a spot-gel serum. Both remained physically stable over four weeks at 4 oC, 25 oC and 40 oC. The cleanser inhibited Cutibacterium acnes and Staphylococcus epidermidis, producing inhibition zones of 33.5 and 24.0 millimetres respectively. It also strongly suppressed biofilm formation in both single- and mixed-species cultures. The serum showed no detectable antibacterial activity.

The findings suggest that chemical antioxidant potency alone is insufficient for selecting cosmetic ingredients. Biological safety, formulation chemistry and microbial interactions should be considered too.

Fig. 1. Total phenolic content (TPC), total flavonoid content (TFC), and total triterpenoid content (TTC) of the ATPS extracts (N10, N12, and N14) compared with the crude extract. TPC is expressed as mg gallic acid equivalents (GAE) per g extract, TFC as mg quercetin equivalents (QE) per g extract, and TTC as mg betulinic acid equivalents (BAE) per g extract. Bars represent mean values, and error bars denote the associated variability (SD).

Fig. 2. DPPH radical-scavenging activity of ATPS-derived extracts (N10, N12, and N14) compared with the crude extract. Dose–response curves show the percentage of DPPH scavenging as a function of extract concentration (µg/mL); symbols represent experimental measurements and solid lines indicate nonlinear regression fits used to estimate IC₅₀ values. Ascorbic acid was used as the positive control (IC₅₀ = 2.006 µg/mL).

Fig. 3. Time-dependent zebrafish survival following exposure to crude extract versus ATPS extract N12. Kaplan–Meier–type survival plots for AB-strain zebrafish monitored for 72 h after treatment with (A) crude extract (AB.Crude) or (B) ATPS extract N12 (AB.N12) at 25, 50, 100, 150, 200, and 400 µg/mL. The y-axis represents survival rate, and the x-axis reports exposure time (hours). The negative control (untreated zebrafish) maintained 100% survival throughout all observations.

Fig. 4. Protective effect of the crude extract against oxidative stress in the zebrafish H2O2 challenge model. Kaplan–Meier type survival curves (survival rate, %) were recorded over the indicated exposure period for zebrafish treated with SF at the concentration of 40 µM (positive control), H2O2 alone (oxidative-stress control), and H2O2 in the presence of the crude extract (test group; dosing as indicated in the experimental section).

Fig. 5. Nrf2 pathway responsive gene expression in zebrafish after treatment with the crude extract. Relative mRNA levels (fold change vs. negative control) of gstp1 and prdx1 (peroxiredoxin 1), two downstream target genes of the Nrf2 antioxidant-response pathway, were quantified by RT–qPCR in AB-strain zebrafish following exposure to 40 µM sulforaphane AB.SF (+) (positive control for Nrf2 activation) and crude extract (50 μg/mL) AB.Crude. Asterisks indicate statistical significance for the indicated comparisons: p < 0.01 (**), p < 0.001 (***), and p < 0.0001 (****); ns, not significant.

Fig. 6. Biofilm biomass (OD590) of Cutibacterium acnes and Staphylococcus epidermidis grown as mono-cultures or co-cultures and treated with 2% salicylic acid (SA), cleanser (CL), serum (SR), crude four-herb extract (HE), or the individual herbal extracts including Houttuynia cordata (HC), Scutellaria baicalensis (SB), Chamaecyparis obtusa (CO), and Artemisia capillaris (AC). Biofilms were quantified by crystal violet staining and measured at OD590 after (A) C. acnes mono-culture for 48 h, (B) S. epidermidis mono-culture for 48 h, and co-culture at initial C. acnes:S. epidermidis inoculation ratios of 5:5 for (C) 24 h and (D) 48 h, 7:3 for (E) 24 h and (F) 48 h. Asterisks indicate statistical significance for the indicated comparisons: *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001; ns, not significant.

Contact the author:

Minh Hien Nguyen

Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Health Sciences, Ho Chi Minh City 75308, Vietnam

Research Center for Discovery and Development of Healthcare Products, Vietnam National University, Ho Chi Minh City 71309, Vietnam

Vietnam National University Ho Chi Minh City, Ho Chi Minh City 71309, Vietnam

nmhien@uhsvnu.edu.vn

Jin-Han Park

Department of Cosmetic Science, Daegu Haany University, Gyeongbuk 38610, Republic of Korea

jinhan@dhu.ac.kr

Conflict of interest:

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

See the article:

https://www.sciencedirect.com/science/article/pii/S2950306X26000257#coi0005

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