A wrinkle in time : the effect of Persicaria senegalensis (Meisn.) Soják on the maintenance of the dermal matrisome in photoageing skin

Ageing is characterised by oxidative stress, abnormal proteolysis, and inflammation. Identifying multiple potentially therapeutic mechanisms of action provides a multi-faceted and holistic approach to natural well-ageing strategies. Persicaria senegalensis (Meisn.) Soják is traditionally used for hemorrhoids, malaria, skin troubles, syphilis, and livestock ailments. Bioactivity includes anti-feedant, sub-clinical mastitis, larvicidal, molluscicidal, anticancer, antibacterial, and anti-diabetes activities. Fermentation and gold nanoparticles offer potential advantages including diminished toxicity, enhanced bioactivity, increased bioavailability, targeted delivery, and increased phytochemical load. This study investigated the anti-ageing bioactivity of the crude ethanolic (PS), Bifidobacterium bifidum fermented (PSF), and gold nanoparticle (PS-AuNP) extracts of P. senegalensis for the first time. PS exhibited noteworthy elastase inhibition (IC50 56.07 ± 0.85 μg/mL), significantly increased elastin production, and reduced the concentration of inflammatory cytokines in dermal fibroblasts. Liquid-liquid partitioning revealed the n-butanol partition to exhibit improved elastase inhibition (IC50 0.29 ± 0.36 μg/mL). 1-(2-Methoxyphenyl)-3-phenylprop-2-en-1-one was isolated for the first time from the n-butanol partition but exhibited no anti-elastase activity at 100 μg/mL. PSF displayed significantly improved elastase inhibition (IC50 14.56 ± 1.27 μg/mL) while PS-AuNPs displayed lower anti-elastase activity (IC50 139.73 ± 17.98 μg/mL) but noteworthy collagenase inhibition (95.64 ± 6.67% at 100 μg/mL). PS and PSF were weakly cytotoxic while PS-AuNPs were moderately cytotoxic on human keratinocytes and dermal fibroblasts in vitro. Notably, PS and PSF enhanced the binding affinity between MMP-9 and TIMP-1 as a novel mechanism of action. This is the first study to investigate the effect of a plant extract on the binding affinity of an enzyme and ligand. PS and PSF were subjected to human irritancy and efficacy studies. PS was classified as a mild irritant, while PSF was a non-irritant, suggesting that fermentation improved the skin compatibility properties of the extract. Both samples significantly reduced the appearance of fine lines and wrinkles after 28 days of application. This is the first report on the anti-ageing potential of P. senegalensis, reporting 1-(2-methoxyphenyl)-3-phenylprop-2-en-1-one isolated for the first time in this species, a novel mechanism of action (TIMP-1/MMP-9 biding modulation) and validated findings in a human study.