Cosmetic Anti-Aging Potential of the Traditional Thai Longevity Formula Mai-Kae-Den-Klong: Mechanistic Insights from Enzyme-Based Bioassays and In Silico Analysis

Skin aging is associated with oxidative stress, extracellular matrix degradation, and dysregulation of melanogenesis, leading to wrinkles, loss of elasticity, and hyperpigmentation. Natural plant-derived compounds have attracted increasing interest as multifunctional cosmetic ingredients due to their antioxidant and anti-aging properties. Mai-Kae-Den-Klong (MKDK), a traditional Thai longevity herbal formula composed of Albizia procera (Roxb.) Benth., Cyperus rotundus L., Diospyros rhodocalyx Kurz, Piper nigrum L., Streblus asper Lour., and Tinospora crispa (L.) Hook.f. & Thomson, has historically been used to promote vitality and healthy aging; however, its potential application as a cosmetic anti-aging ingredient remains scientifically unexplored. Therefore, this study investigated the anti-aging potential of MKDK extract using integrated enzyme-based bioassays and in silico approaches. Phytochemical profiling of the ethanolic extract was performed using LC-MS analysis, revealing diverse bioactive constituents, including flavonoids, phenolic glycosides, alkaloids, and terpenoids, with (−)-epicatechin, procyanidin B1, and piperine identified as major metabolites. Antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays, while inhibitory activities against tyrosinase, collagenase, elastase, and hyaluronidase were assessed to determine skin anti-aging potential. The extract exhibited strong antioxidant activity, with IC50 values of 17.23 ± 2.11 µg/mL for DPPH and 11.87 ± 1.77 µg/mL for ABTS assays. In addition, the extract demonstrated inhibitory effects against tyrosinase (IC50 = 41.25 ± 1.56 µg/mL), elastase (IC50 = 49.51 ± 3.69 µg/mL), collagenase (IC50 = 61.54 ± 2.88 µg/mL), and hyaluronidase (IC50 = 63.74 ± 6.32 µg/mL), suggesting multifunctional anti-aging properties associated with skin brightening and extracellular matrix preservation. Network pharmacology analysis predicted multiple aging-related signaling pathways, particularly the FoxO signaling pathway, which is associated with oxidative stress regulation and longevity. Molecular docking analysis further demonstrated favorable binding affinities of procyanidin B1, epicatechin, and piperine toward skin-aging-related enzymes, supporting their potential contribution to the observed bioactivities. Overall, these findings suggest that MKDK possesses promising cosmeceutical potential as a natural multifunctional anti-aging ingredient and provides scientific support for the application of traditional Thai herbal formulations in cosmetic and skin health products.