First identification of an amphibian-derived peptide with anti-vascular aging activity.
Amphibian skin just delivered a research surprise. A team from Kunming Medical University isolated AL-VI10, a new peptide, and showed it can slow down vascular aging in preclinical models. This is the first time an amphibian-derived peptide has shown such anti-aging activity in blood vessels.
Zool Res
by Liu X, Liu J, Li B et al.
“First identification of an amphibian-derived peptide with anti-vascular aging activity. Liu X(1), Liu J(1), Li B(2), Qian ZH(1), Zhang GR(1), Gan HY(1), Li ZR(1), Han XY(1), Wang Z(1), Li YS(1), Zheng XY(1), Wang LT(1), Yin SG(1), Su WR(3), He L(4), Wang Y(5), Luo MY(6), Yang XW(7). Author information: (1)Key Laboratory of Skin and Mucosal Injury Repair, Regeneration & Active Peptides of Yunnan Provincial Department of Education, Regenerative Medicine Research Center, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan 650500, China. (2)Department of Cardiac and Vascular Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650500, China. (3)Yunnan Yunke Characteristic Plant Extraction Laboratory Co., Ltd., Kunming, Yunnan 650106, China. (4)Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China. E-mail: drheli2662@126.com. (5)Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming, Yunnan 650504, China. E-mail: wangying_814@163.com. (6)Key Laboratory of Skin and Mucosal Injury Repair, Regeneration & Active Peptides of Yunnan Provincial Department of Education, Regenerative Medicine Research Center, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan 650500, China. E-mail: luomingying0403@163.com. (7)Key Laboratory of Skin and Mucosal Injury Repair, Regeneration & Active Peptides of Yunnan Provincial Department of Education, Regenerative Medicine Research Center, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan 650500, China. E-mail: yangxinwang@kmmu.edu.cn. Vascular aging is a principal driver of cardiovascular morbidity and mortality, and effective prevention of age-related vascular pathologies depends on interventions that target fundamental molecular and cellular aging pathways. The present study investigated the anti-vascular aging activity of AL-VI10, a novel bioactive peptide derived from amphibian skin, together with the underlying mechanism. Notably, AL-VI10 exhibited excellent biosafety, with no detectable cytotoxic or hemolytic activity, and showed potent free radical scavenging capacity, enhanced antioxidant enzyme activity, and reduced reactive oxygen species (ROS) accumulation. In a D-galactose-induced mouse model of aging, AL-VI10 significantly attenuated vascular aging-associated phenotypes, including increased medial thickness, elevated expression of inflammatory cytokines, and up-regulation of matrix metalloproteinase levels, while simultaneously promoting autophagy. In hydrogen peroxide (H 2O 2)-induced senescent human umbilical vein endothelial cells, AL-VI10 reduced senescence-associated β-galactosidase (SA-β-gal) activity, down-regulated senescence markers p53 and p21, enhanced endothelial proliferation and migration, and increased endothelial nitric oxide synthase expression. Mechanistic analyses showed that AL-VI10 up-regulated silent information regulator 1 (SIRT1) and nuclear factor erythroid 2-related factor 2 (Nrf2). Pharmacological inhibition of SIRT1 suppressed AL-VI10-induced Nrf2 activation and weakened its anti-senescence effects, whereas inhibition of Nrf2 reversed ROS reduction and impaired endothelial recovery. Further analysis demonstrated direct binding of AL-VI10 to the extracellular domain of leukocyte differentiation antigen CD44 (CD44), and CD44 knockdown abolished activation of the SIRT1-Nrf2 axis and eliminated the anti-senescence activity of AL-VI10. These findings indicate that AL-VI10 alleviates vascular aging through CD44-dependent activation of SIRT1-Nrf2 signaling and identify amphibians as a promising source of bioactive compounds for anti-aging therapy. Publisher: 血管衰老是心血管疾病发病率和死亡率的主要驱动因素。针对衰老相关的核心分子及细胞衰老通路进行调控，可有效阻止血管衰老相关病变。该研究旨在评估一种源自两栖动物皮肤的新型活性肽AL-VI10的抗血管衰老作用及其潜在机制。结果显示，AL-VI10具有良好的生物安全性，无细胞毒性与溶血活性，并具有较强的自由基清除能力，能够提升抗氧化酶活性，减少活性氧（ROS）的积累。在D-半乳糖诱导的衰老小鼠模型中，AL-VI10显著改善了血管衰老相关表型，包括降低血管中膜的厚度、减少炎症因子表达和基质金属蛋白酶水平，同时促进自噬。在过氧化氢（H 2O 2）诱导的人脐静脉内皮细胞衰老模型中，AL-VI10降低了衰老相关β-半乳糖苷酶(SA-β-gal）活性，下调衰老标志物p53和p21表达，刺激内皮细胞增殖迁移，并上调内皮型一氧化氮合酶表达。机制研究表明，AL-VI10可上调沉默信息调节因子1（SIRT1）和核因子E2相关因子2（Nrf2）的表达。抑制SIRT1会减弱AL-VI10对Nrf2激活作用并降低其抗衰老效应，而抑制Nrf2则会逆转ROS的减少并损害内皮功能恢复。此外，AL-VI10可与白细胞分化抗原CD44的胞外结构域结合，敲低CD44可抑制SIRT1-Nrf2通路激活，并降低AL-VI10的抗血管衰老活性。以上结果表明，AL-VI10通过CD44介导的SIRT1-Nrf2信号通路激活发挥抗血管衰老作用，凸显了两栖类动物是发掘新型抗衰老生物活性物质的宝贵资源。.”
Vascular aging is a massive problem in research, driving much of the risk behind heart disease and stroke. AL-VI10 takes a direct shot at the issue. The peptide didn’t just work in a petri dish — it showed results in a mouse aging model. Researchers saw less thickening of vessel walls, lower inflammation, and better antioxidant defenses. No cytotoxicity, no hemolysis. Just clean activity.
Here’s what stands out in the data:
Potent free radical scavenging
Reduced markers of cellular senescence (p53, p21, SA-β-gal) in human endothelial cells
Enhanced autophagy, cell proliferation, and migration
Boosted SIRT1 and Nrf2 signaling, both big names in the cellular anti-aging world
Direct binding to CD44, a cell surface molecule that turns out to be critical for the whole process
When SIRT1 or Nrf2 were blocked, AL-VI10 lost much of its punch. Same story when CD44 was knocked down. That’s a clear mechanistic pathway, not just a vague "antioxidant effect." The peptide’s actions look tightly regulated and targeted.
Key takeaway: Amphibians are a goldmine for novel research compounds. AL-VI10 opens the door for more bioactive peptides targeting cellular aging and vascular dysfunction. If you want to dig deeper into new peptide discoveries, check out the peptide research index.
The peptide field keeps getting more interesting — and the source material keeps getting wilder.
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