Development on potential skin anti-aging agents of Cosmos caudatus Kunth via inhibition of collagenase, MMP-1 and MMP-3 activities

Loo YC 1 , Hu HC 2 , Yu SY 3 , Tsai YH 4 , Korinek M 1 , Wu YC 5 Show all authors , Chang FR 6 , Chen YJ 7

Affiliations 

  • 1 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
  • 2 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Szeged, Szeged, Hungary
  • 3 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Institute of Pharmacognosy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary
  • 4 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Department of Pharmacy and Master Program, College of Pharmacy and Health Care, Tajen University, Pingtung County 90741, Taiwan
  • 5 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan; Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung 404, Taiwan; Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung 404, Taiwan. Electronic address: yachwu@kmu.edu.tw
  • 6 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. Electronic address: aaronfrc@kmu.edu.tw
  • 7 Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Department of Fragrance and Cosmetic Sciences, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan. Electronic address: yjchen@cc.kmu.edu.tw
Phytomedicine, 2023 Feb;110:154643.
PMID: 36623444 DOI: 10.1016/j.phymed.2023.154643

Abstract

BACKGROUND: Skin aging is associated with degradation of collagen by matrix metalloproteinases (MMPs), which leads to loss of skin elasticity and formation of wrinkles. Cosmos caudatus Kunth (CC) has been traditionally claimed as an anti-aging agent in Malaysia. Despite its well-known antioxidant activity, the anti-aging properties of CC was not validated.

PURPOSE: This study aimed to investigate the anti-aging potential of CC extracts and fractions, particularly their inhibition of collagenase, MMP-1 and MMP-3 activities in human dermal fibroblasts CCD-966SK, followed by isolation, identification and analysis of their bioactive constituents.

STUDY DESIGN AND METHODS: DPPH assay was firstly used to evaluate the antioxidant activity throughout the bioactivity-guided fractionation. Cell viability was determined using MTS assay. Collagenase activity was examined, while MMP-1 and MMP-3 expression were measured using qRT-PCR and western blotting. Then, chemical identification of pure compounds isolated from CC fractions was done by using ESIMS, 1H and 13C NMR spectroscopies. HPLC analyses were carried out for bioactive fractions to quantify the major components.

RESULTS: Throughout the antioxidant activity-guided fractionation, fractions CC-E2 and CC-E3 with antioxidant activity and no toxicity towards CCD-966SK cells were obtained from CC 75% ethanol partitioned layer (CC-E). Both fractions inhibited collagenase activity, MMP-1 and MMP-3 mRNA and protein expression, as well as NF-κB activation induced by TNF-α in CCD-966SK cells. 14 compounds, which mainly consists of flavonoids and their glycosides, were isolated. Quercitrin (14.79% w/w) and quercetin (11.20% w/w) were major compounds in CC-E2 and CC-E3, respectively, as quantified by HPLC. Interestingly, both fractions also inhibited the MMP-3 protein expression synergistically, compared with treatment alone.

CONCLUSION: The quantified CC fractions rich in flavonoid glycosides exhibited skin anti-aging effects via the inhibition of collagenase, MMP-1 and MMP-3 activities, probably through NF-κB pathway. This is the first study reported on MMP-1 and MMP-3 inhibitory activity of CC with its chemical profile, which revealed its potential to be developed as anti-aging products in the future.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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