Lee, Sohyun Youn, Esther Tran, Son Hung Bae, Won-Young Nguyen, Uyen Tran Tu Ho, Phuong Ly Kim, Ji Hoon Park, Keunwan Kim, Chul Young Kang, Kyungsu 2025-09-23T03:00:45Z 2025-09-23T03:00:45Z 2025-09-16 2026-01 0378-8741 https://pubs.kist.re.kr/handle/201004/153219 Ethnopharmacological relevance Lycium chinense Miller has long been used in East Asian medicine for muscle and bone support. Kukoamine A (KA), a bioactive compound from its root bark, has not been previously studied for its potential to counteract age- and heat-induced locomotor decline. Aim of the study This study aims to investigate whether KA improves mobility in aged animal models and to elucidate its underlying mechanism. Materials and methods Caenorhabditis elegans were treated with KA, and their growth rate, locomotor performance under aging and heat-stressed conditions were evaluated. ROS levels, muscle mitochondrial morphology, and mitochondrial membrane potential were measured via fluorescence microscopy. The nuclear localization of SKN-1 and the expression levels of HSF-1 and its downstream HSPs were measured in the transgenic GFP-tagged strains. The necessity of HSF-1 and HSPs was tested using corresponding mutant worms. Results KA treatment ameliorated the age-related decrease in swimming activity and preserved muscle mitochondrial morphology in aged worms. Furthermore, it attenuated the age-associated increase in ROS levels. The treatment significantly increased the expression of HSF-1, as well as its downstream targets, HSP-6, HSP-4, and HSP-16.2, whereas SKN-1 nuclear translocation was not observed with the 24 h of L4-stage regimen. The locomotor benefits of KA supplementation were abolished in HSF-1 and HSP-deficient mutants, with speed preserved only in the HSP-16.2 mutant. Furthermore, it prevented heat stress-induced mobility impairment. Conclusion KA treatment mitigated age-related locomotor decline by enhancing mitochondrial health and inducing HSF-1–mediated HSP activation across multiple cellular compartments. English Elsevier BV Kukoamine A from the root bark of Lycium chinense Miller enhances mobility in an aged Caenorhabditis elegans model by regulating mitochondrial function through HSF-1-mediated upregulation of heat shock proteins Article 10.1016/j.jep.2025.120469 3 Journal of Ethnopharmacology, v.354 Journal of Ethnopharmacology 354 Y 001565292500004 2-s2.0-105014287042 Plant Sciences Chemistry, Medicinal Integrative & Complementary Medicine Pharmacology & Pharmacy Plant Sciences Pharmacology & Pharmacy Integrative & Complementary Medicine Article STRESS-RESISTANCE LIFE-SPAN CORTEX PROTEOSTASIS ACTIVATION INHIBITOR EXTRACT Kukoamine A(KA) Caenorhabditis elegans HSF-1 Heat shock protein Mitochondria List of compounds studied: Kukoamine A (PubChem CID: 5318865) Prednisone (PubChem CID: 5865) Baicalein (PubChem CID: 5281605)