Mechanistic studies on protective effects of total flavonoids from Ilex latifolia Thunb. on UVB-radiated human keratinocyte cell line (HaCaT cells) based on network pharmacology and molecular docking technique

Yunge Ma; Yingyan Li; Yike Yao; Tao Huang; Chong Lan; Liyan Li

doi:10.1111/php.13953

Mechanistic studies on protective effects of total flavonoids from Ilex latifolia Thunb. on UVB-radiated human keratinocyte cell line (HaCaT cells) based on network pharmacology and molecular docking technique

Photochem Photobiol. 2024 Apr 21. doi: 10.1111/php.13953. Online ahead of print.

Authors

Yunge Ma¹, Yingyan Li¹, Yike Yao¹, Tao Huang², Chong Lan^{2

3}, Liyan Li^{2

3}

Affiliations

¹ Pharmacy College, Henan University, Kaifeng, China.
² Medical School, Huanghe Science & Technology University, Zhengzhou, China.
³ Zhengzhou Key Laboratory of Drug Screening and Activity Evaluation, Huanghe Science & Technology University, Zhengzhou, China.

PMID: 38644599
DOI: 10.1111/php.13953

Abstract

The aim of the present research is to investigate anti-UVB radiation activity of total flavonoids from Ilex latifolia Thunb. (namely large-leaved Kuding tea) on human keratinocyte cell line (HaCaT cells) based on network pharmacology and molecular docking technique. Network pharmacology was used to screen target genes of active ingredients from Ilex latifolia Thunb. associated with UVB irradiation. The possible signaling pathways were analyzed by KEGG enrichment and verified by cellular experiments. Molecular docking was used to assess the affinity between the active ingredients and the core targets. The prediction of network pharmacology and molecular docking was identified by series experiment in UVB-irradiated HaCaT cells. Network pharmacology results showed that the active ingredients of Ilex latifolia Thunb. for anti-UVB irradiation were mainly flavonoids, and the possible signaling pathways were involved in PI3K-AKT, apoptosis, MAPKs, NF-κB, and JAK-STAT3. Molecular docking indicated key binding activity between AKT1-Glycitein, STAT3-Formononetin, CASP3-Formononetin, TNF-Kaempferol, CASP3-Luteolin, and AKT1-Quercetin. The total flavonoid pretreatment (0.25-1.0 mg/mL) down-regulated the expression of IL-6, IL-1β, and TNF-α in the cells determined by ELISA. The expression of phosphor PI3K, phosphor AKT, phosphor JAK, phosphor STAT3, phosphor JNK, and phosphor p38 MAPKs and COX-2 proteins in cytosolic and NF-κB p65 protein in nucleus were down-regulated and determined by western blot. It also protected UVB-irradiated cells from apoptosis by reducing apoptosis rate and down-regulating active-caspase 3. In a word, the total flavonoid treatment protected HaCaT cells from UVB injuries effectively, and the potential mechanism involves PI3K-AKT, JAK-STAT3, MAPK, and NF-κB pathway by anti-inflammatory and apoptosis action in cells. The mechanism in vivo experiment needs to be further confirmed in future.

Keywords: Ilex latifolia Thunb.; anti‐UVB irradiation; anti‐inflammatory; molecular docking; network pharmacology; total flavonoids.

Abstract

Grants and funding