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A Scorpion Venom-Derived Peptide M6 Endowed with Anti-Aging Ability via Enhanced Antioxidant Activity in Cells,
Siyuan Luo1,2, Haixin Qin1,2,3,4, Weimin Zuo1,2
1Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau.
Abstract:
With an aging population and the prevalence of oxidative damage-related ailments, the quest for effective antioxidant and anti-aging agents has emerged as a focal point of biomedical research. Within this domain, peptides have garnered considerable attention for their potential activities. Hence, the current study investigates the antioxidant and anti-aging properties of a scorpion venom-derived peptide M6. We demonstrated that this peptide decreases H2O2-dependent apoptosis by binding to the TNFR1 receptor, which activates the NF-κB signaling pathway, thereby enhancing the capacity of cells to mitigate oxidative damage induced by H2O2 treatment. Moreover, M6 prolonged the lifespan of C. elegans and enhanced their thermal stress resistance. Further studies demonstrated that M6 inhibits the IIS/PI3K/AKT signaling pathway and activates daf-16 and skn-1 (homologous to Nrf-2), thereby enhancing the antioxidant capacity of nematodes and alleviating oxidative damage. Furthermore, M6 also alleviated D-galactose-induced oxidative damage in mice by enhancing the activity of catalase and superoxide dismutase. We also showed that M6 treatment protects liver and kidney tissues from oxidative damage induced by D-galactose. These results highlight the beneficial antioxidant and anti-aging properties of the peptide M6, which appear to be a promising lead for addressing related diseases and mitigating the effects of aging.
Insights
Scorpion venom peptide M6 shows potent antioxidant and anti-aging effects. It protects cells from oxidative stress, extends lifespan in C. elegans, and alleviates damage in mice, offering a promising therapeutic lead.
Area of Science:
- Biomedical Research
- Aging and Oxidative Stress
- Peptide Therapeutics
Background:
- Aging populations face increased oxidative damage-related diseases.
- Peptides are increasingly recognized for their therapeutic potential.
- Effective antioxidant and anti-aging agents are in high demand.
Purpose of the Study:
- To investigate the antioxidant and anti-aging properties of M6, a peptide derived from scorpion venom.
- To elucidate the molecular mechanisms underlying M6's protective effects.
Main Methods:
- Cellular assays assessing H2O2-induced apoptosis and oxidative damage.
- Lifespan and stress resistance studies in C. elegans.
- Molecular pathway analysis including TNFR1, NF-κB, IIS/PI3K/AKT, daf-16, and skn-1.
- Biochemical assays measuring antioxidant enzyme activity (catalase, SOD) in mice.
- Histopathological examination of liver and kidney tissues in mice.
Main Results:
- M6 reduced H2O2-induced apoptosis by activating TNFR1 and the NF-κB pathway.
- M6 extended C. elegans lifespan and improved thermal stress resistance.
- M6 inhibited the IIS/PI3K/AKT pathway and activated daf-16 and skn-1 in nematodes, boosting antioxidant capacity.
- M6 alleviated D-galactose-induced oxidative damage in mice, enhancing catalase and SOD activity.
- M6 protected mouse liver and kidney tissues from oxidative damage.
Conclusions:
- M6 exhibits significant antioxidant and anti-aging properties.
- The peptide M6 demonstrates therapeutic potential for age-related diseases and mitigating aging effects.
- M6's mechanisms involve modulation of key cellular signaling pathways and enhancement of endogenous antioxidant defenses.
