This Bitter Compound Promotes Mitochondrial Health and Prevents Muscle Aging!

This Bitter Compound Promotes Mitochondrial Health and Prevents Muscle Aging!

The olive (Olea europaea L.) is a plant species belonging to the genus Olea in the Oleaceae family, primarily cultivated in Mediterranean coastal countries of southern Europe and is a subtropical tree species of the Mediterranean type. China began introducing olive cultivation in 1964, and after decades of development, it has now formed a new characteristic industry with thousands of acres of planting. As far back as several thousand years ago, olive leaves have been used in folk medicine to treat fevers and other diseases, such as malaria. The pharmacological activity of olive leaves primarily stems from their polyphenolic compounds, with oleuropein being the most abundant.

Oleuropein is a phenolic iridoid glycoside composed of hydroxytyrosol, glucose molecules, and oleuropeinic acid. Discovered in 1908 by Bourquelot and Vintilesco, it is distributed throughout the entire olive tree, though its concentration varies across different parts. It is particularly abundant in immature olive fruits and leaves, with a dry matter concentration of up to 140 mg/g in young olives and 60-90 mg/g in leaves. This compound is responsible for the distinctive bitterness of unripe and unprocessed olives.

1. Promote mitochondrial health and prevent muscle aging

Last year, a new study published in the journal Cell Metabolism revealed that natural polyphenol oleuropein, as a novel food source molecule, can specifically target mitochondrial calcium uniporter (MCU) to stimulate mitochondrial bioenergy metabolism and improve muscle performance.

Mitochondria are crucial for cellular energy production, and their dysfunction is closely related to aging and chronic diseases. In skeletal muscle, mitochondrial metabolism is crucial for maintaining energy requirements during exercise. The decline in mitochondrial function is a key factor in muscle atrophy, manifested as a decrease in muscle mass, strength, and walking speed. 

The regulation of mitochondrial calcium (mtCa2+) has a direct effect on oxidative metabolism and is involved in regulating the function of skeletal muscle. The uptake of calcium in mitochondria is controlled by the mitochondrial calcium uniporter protein (MCU), which is a multi protein complex composed of MCU channels that transport Ca2+on the inner membrane of mitochondria and regulatory subunits that regulate MCU activity to meet cellular metabolic needs.

Research has found that by downregulating mitochondrial calcium uniporter regulatory factor 1 (MCUR1), the ability of model organisms and humans to uptake mtCa2+during aging decreases. Cell and in vivo gene rescue experiments have shown that the reduction of MCUR1 directly leads to impaired mitochondrial energy metabolism. 

In order to identify a novel nutritional solution that can stimulate mitochondrial bioenergy and reverse age-related decline, the research team further screened natural molecules that activate mtCa2+using high-throughput (HT). It was found that oleuropein and its deglycosylated metabolites bind to the MICU1 regulatory subunit of MCU, stimulating mitochondrial uptake of Ca2+, thereby briefly increasing mtCa2+concentration at the physiological level, and activating PDH dephosphorylation through Ca2+dependent phosphatase PDP.

Research has shown that natural polyphenol oleuropein is an effective and selective activator of MCUs, which stimulates mitochondrial respiration and ATP production through mtCa2+uptake and has the potential to improve skeletal muscle.

2. More benefits of oleuropein

Olive bitter glycoside has various biological activities, can participate in the body's metabolic processes, and has a relieving and therapeutic effect on various common diseases. In recent years, with the deepening of research on the biological activity of oleuropein, oleuropein and its aglycones have antioxidant, anti-inflammatory, cardioprotective, neuroprotective, and anti-aging effects.

1) Antioxidant 

The antioxidant activity of oleuropein is achieved through multiple mechanisms, with the key being the presence of ortho phenolic groups in its molecular structure, which can act as hydrogen donors, effectively scavenge reactive oxygen species (ROS), and stabilize oxygen radicals through intramolecular hydrogen bonding, thereby exerting antioxidant effects. 

Research has shown that oleuropein exhibits similar effects to ascorbic acid and alpha tocopherol in vitro experiments, with the ability to clear nitric oxide and promote upregulation of inducible nitric oxide synthase (iNOS) expression in cells [4]. In addition, oleuropein can effectively remove hypochlorous acid, a strong oxidant produced by neutrophil myeloperoxidase at the site of inflammation, which can cause damage to proteins including enzymes.

2) Anti inflammatory

Inflammation is the body's defense response to injury or infection, the common basis for the development of many diseases, and plays a key role in atherosclerosis, diabetes, metabolic syndrome, neurodegenerative diseases and other diseases. 

In the 2006 PrediMED study, it was first revealed that consuming extra virgin olive oil (EVOO) in the Mediterranean diet (MD) has significant anti-inflammatory effects, manifested by significantly reduced levels of C-reactive protein (CRP), interleukin-6 (IL-6), endothelial and monocyte adhesion molecules (ICAM-1 and VCAM-1), and chemokines in serum. 

Subsequent in vitro and in vivo experimental studies have further confirmed that compared to other phenols in EVOO, oleuropein is the most effective inhibitor of inducing cells to produce inflammatory factors. Olive bitter glycoside exerts its anti-inflammatory effects by regulating lipoxygenase activity, reducing the production of leukotriene B4, inhibiting the synthesis of pro-inflammatory cytokines, and regulating inflammation related parameters.

3) Neuroprotective effect

Many neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease, are caused by the gradual loss of neuronal structure and function. A study showed that compared with the untreated control group, intraperitoneal injection of oleuropein daily for 6 months in elderly rats can enhance the antioxidant enzyme activity in their brains. Meanwhile, rats treated with oleuropein showed an increase in the number of neurons in the substantia nigra, indicating that oleuropein helps prevent the loss of dopaminergic neurons. 

According to reports, oleuropein can non covalently bind to amyloid beta (A β) 1-40 peptides, thereby reducing or even preventing the aggregation of A β. In addition, oleuropein can also inhibit Tau protein, which is a known abnormal protein that forms amyloid positive aggregates in Alzheimer's disease.

4) Anti aging

Human fibroblasts undergo replicative aging under the influence of genetic and environmental factors. The decline in proteasome function is a characteristic of the aging process, but its increased expression helps to delay cellular aging. Research has found that oleuropein can effectively enhance proteasome activity, possibly by changing its conformation. Olive bitter glycoside treatment of early passaged human embryonic fibroblasts can reduce intracellular ROS levels, decrease oxidative proteins, maintain proteasome function, thereby delaying the appearance of aging morphology during replicative aging and extending cell lifespan by about 15%.

3. Market prospects of oleuropein

Olive leaves, as a byproduct of olive processing, generate over one million tons of waste annually, leading to significant waste of resources and potential environmental damage. However, the active ingredient oleuropein in olive leaves is gradually gaining market attention. 

According to Market Research Intellect, the market size of oleuropein reached 860 million US dollars in 2023 and is expected to grow to 1.42 billion US dollars by 2031, with a compound annual growth rate of 7.2% during this period. This growth trend highlights the potential value of olive leaves and the importance of their comprehensive utilization.

4. Application Case

Roex dietary supplements contain 500mg of olive leaf extract (containing 20% oleuropein), which can help maintain a healthy balance of cytokines in the body and regulate immune and inflammatory responses.

SRW Cel ³ contains apigenin, fisetin, oleuropein, berberine, and EGCG, which support autophagy and healthy cell renewal.

The tea tree shampoo stick launched by Bellalush adds oleuropein from olive leaves, utilizing natural antioxidant properties to provide a revitalizing and nourishing hair cleaning experience.