SS31 30mg*10vials

▎SS-31 Structure

▎SS-31 Research

What is the research background of SS-31?

SS-31 is an opioid peptide derived from pheromone peptide. It was initially discovered during mechanistic studies of pheromone peptide, which exhibits strong analgesic effects and excellent cell membrane permeability, leading to the identification of the mitochondrial-targeted antioxidant peptide SS-311. Its research background is also closely related to studies on diseases associated with mitochondrial dysfunction. As the “powerhouse” of the cell, mitochondrial dysfunction is associated with the onset and progression of various diseases, such as ischemia-reperfusion injury, neurodegenerative diseases, heart failure, and muscle aging, all of which are related to oxidative stress caused by excessive free radical production. SS-31 effectively alleviates oxidative stress and protects mitochondrial function.

What is the mechanism of action of SS-31?

Regulating membrane surface electrostatic properties: 

SS-31 interacts with the mitochondrial membrane, altering the electrostatic properties of the membrane surface to influence the distribution of ions and basic proteins at the membrane interface. Studies have shown that SS-31 can alter the distribution of divalent cations in the membrane interface region, thereby reducing the energy burden of mitochondrial calcium stress and maintaining mitochondrial membrane stability ^[1,2].

Influencing lipid arrangement: 

This peptide can induce reversible changes in lipid arrangement. Although it does not disrupt the stability of the bilayer at high binding concentrations, it may indirectly influence mitochondrial membrane-related physiological processes, such as membrane protein function and membrane fluidity, thereby exerting a positive effect on mitochondrial function^[1,2].

Inhibition of inflammatory responses: 

In studies related to sepsis, SS-31 was found to reduce inflammatory factors such as interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor -α (TNF-α), thereby mitigating the damage caused by inflammatory responses to tissues and organs^[3].

Reducing oxidative stress: 

SS-31 can enhance the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase, reduce the levels of oxidative products such as malondialdehyde (MDA), and decrease the production of reactive oxygen species (ROS), thereby mitigating oxidative stress-induced damage to cells and tissues and protecting the normal functions of mitochondria and cells^[3] .

Regulating mitochondrial dynamics: 

In studies on sepsis-associated encephalopathy, SS-31 can inhibit the excessive activation of mitochondrial fission-related proteins such as dynamin-related protein 1 (Drp1), reduce excessive mitochondrial fission, maintain normal mitochondrial morphology and function, and thereby improve cognitive function^[4] .

Figure 1. Accumulation and antioxidant mechanism of Szeto-Schiller-31 (SS-31)^[5].

Source: MDPI

What are the functions and applications of SS-31?

Functions

Cellular protective effects: 

In a hydrogen peroxide (H₂O₂) induced oxidative stress damage model of ARPE-19 cells, SS-31 can increase cell survival rate, reduce intracellular ROS content, maintain mitochondrial membrane potential, and lower cell death rate, demonstrating significant protective effects on cells damaged by oxidative stress.

Improvement of organ function  

Heart: In animal models of myocardial ischemia-reperfusion injury, pretreatment with SS-31 before reperfusion significantly reduced myocardial infarct size, with efficacy positively correlated with the severity of myocardial ischemia; during the ischemic period, SS-31 reduced the no-flow zone in the hypoperfused myocardial area and improved the incidence and severity of arrhythmias. In sepsis-induced myocardial dysfunction, SS-31 can restore myocardial morphological damage, inhibit inflammatory responses, improve myocardial energy deficiency, maintain mitochondrial membrane potential, and protect the heart from damage^[3].

Lungs: SS-31 can reduce inflammatory exudation and edema in lung tissue, lower lung histology scores, regulate inflammatory factors and oxidative stress-related indicators, and improve acute lung injury.

Brain: Continuous intraperitoneal injection of SS-31 can improve cognitive function and survival rate in mice, reduce hippocampal inflammation, ROS production, and mitochondrial hyperdivision. In an aged mouse model, SS-31 treatment induces changes in the microvascular proteome of the cerebral cortex, affecting the expression of mitochondrial-related proteins, and has a certain ameliorative effect on age-related microvascular changes in the brain^[4,6].

Applications

Cardiovascular diseases: 

Given its protective effects against myocardial ischemia-reperfusion injury and sepsis-induced myocardial dysfunction, SS-31 holds potential application value in the prevention and treatment of cardiovascular diseases, with the potential to be developed as a novel therapeutic agent for conditions such as myocardial infarction and sepsis-induced cardiomyopathy ^[3].

Pulmonary Diseases: 

For acute lung injury caused by sepsis, SS-31 may serve as an effective therapeutic agent by reducing inflammation and oxidative stress, thereby improving lung function and offering new treatment options for patients with acute lung injury.

Neurological diseases: 

In sepsis-associated encephalopathy and age-related neurological diseases, SS-31 has shown the ability to improve cognitive function, suggesting its potential for development in the treatment of neurological diseases such as Alzheimer's disease and post-sepsis cognitive impairment ^[4,6].

Atherosclerosis: 

Due to its therapeutic effects on ApoE gene-knockout atherosclerotic rats, SS-31 has potential for application in the treatment of atherosclerotic diseases by alleviating oxidative stress and slowing disease progression.

Conclusion

In summary, SS-31 is a mitochondrial-targeted antioxidant peptide that regulates membrane surface electrostatic properties, inhibits inflammation, reduces oxidative stress, and improves mitochondrial dynamics. It protects organs such as the heart, lungs, and brain, alleviates ischemia-reperfusion injury and sepsis-related damage, delays cellular aging, and has certain therapeutic effects in the prevention and treatment of cardiovascular, neurological, and other systemic diseases, as well as atherosclerosis.

About The Author

The above-mentioned materials are all researched, edited and compiled by Cocer Peptides.

Scientific Journal Author

Broome, Sophie C is associated with the Australian Catholic University and the University of Auckland. Her research spans several disciplines, including Sport Sciences, Physiology, Nutrition & Dietetics, Biochemistry & Molecular Biology, and Neurosciences & Neurology. She investigates the effects of exercise on physical performance and health, examining the physiological responses and adaptations to physical activity. Broome also explores the relationship between nutrition and health, and the applications of biochemistry and molecular biology in exercise science. Her work in neurosciences and neurology further adds to our understanding of the nervous system's functions and related disorders, providing valuable theoretical and practical insights into sports science and health research. Broome, Sophie C is listed in the reference of citation [5].

▎Relevant Citations

[1] Mitchell W, Ng E A, Tamucci J D, et al. The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates  surface electrostatics as a key component of its mechanism of action[J]. Journal of Biological Chemistry, 2020,295(21):7452-7469.DOI:10.1074/jbc.RA119.012094.

[2] Mitchell W, Ng E A, Tamucci J D, et al. Molecular Mechanism of Action of Mitochondrial Therapeutic SS-31 (Elamipretide): Membrane Interactions and Effects on Surface Electrostatics[J]. Biorxiv, 2019. DOI:10.1101/735001.

[3] Liu Y, Yang W, Sun X, et al. SS31 Ameliorates Sepsis-Induced Heart Injury by Inhibiting Oxidative Stress and Inflammation[J]. Inflammation, 2019,42(6):2170-2180.DOI:10.1007/s10753-019-01081-3.

[4] Zhong L, Ren X, Ai Y, et al. SS-31 Improves Cognitive Function in Sepsis-Associated Encephalopathy by  Inhibiting the Drp1-NLRP3 Inflammasome Activation[J]. Neuromolecular Medicine, 2023,25(2):230-241. DOI:10.1007/s12017-022-08730-1.

[5] Broome S C, Woodhead J S T, Merry T L. Mitochondria-Targeted Antioxidants and Skeletal Muscle Function[J]. Antioxidants, 2018,7(8},ARTICLE-NUMBER ={107).DOI:10.3390/antiox7080107.

[6] Rutkai I, Seman A, Chandra P, et al. The beneficial effects of SS-31 on aging mice cerebral microvasculature[J]. Physiology, 2023,38.DOI:10.1152/physiol.2023.38.S1.5734232.

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