Table 4.
Effects of HTyr or OLE on skeletal muscle atrophy and osteoporosis and skeletal muscle insulin resistance.
| Model | Compound/Compounds Mix •Treatment | Effects | References |
|---|---|---|---|
| Aged Wistar rats (27-months-old) | LACHI MIX HT: HTyr (47.34%), tyrosol (11.96%), gallic acid (18.49), homovanillic acid (7.07%), catechol (5.80%), caffeic acid (1.66%) •500 µg/Kg/day for 6–8 weeks via gavage |
↑ hindlimb muscle weight; ↑ ion channel conductance of the sarcolemma and contractile function; ↑ ATP-dependent potassium channel activity; ↓ resting cytosolic calcium concentration; ↓ blood creatine kinase | [289] |
| Aged Wistar rats (24-months-old) | Olive leaf extract •100 mg/Kg/day in drinking water for 21 days |
↑ gastrocnemius muscle mass; ↓ markers of sarcopenia (HDAH4, MyoD, myogenin, myostatin); ↑ PGC1α; ↓ pro-inflammatory markers (COX-2, IL-6, IL-1β); ↑ anti-inflammatory cytokine IL-10; ↑ GLUT4 and insulin sensitivity in gastrocnemius explants | [291] |
| Aged Wistar rats (24-months-old) | Olive leaf extract •100 mg/Kg/day in drinking water + Mixture of EVOO (75%) and Algae Oil 25%) •2.5 mL/Kg/day for 21 days via gavage |
↑ gastrocnemius and soleus muscle mass; ↓ sarcopenia-related markers (HDAH4, MyoD, myogenin, myostatin, MURF1, Atrogin-1); ↑ MyHC isoforms; ↑ PGC1α; ↑ anti-inflammatory cytokine IL-10; ↓ macrophage infiltration and ↑ insulin sensitivity in gastrocnemius muscle | [297] |
| Osteoblastic and osteoclastic cells | OLE •100 µM Htyr or OLE •10 or 50 µM HTyr •50 µM |
↑ calcium deposition in differentiating osteoblasts; ↑ ↓ osteoclastic cell formation from mouse spleen cells ↓ intracellular ROS concentration |
[304] |
| Ovariectomized mice as a model of osteoporosis | HTyr or OLE •10 mg/Kg at 3-day intervals for 28 days via gavage |
↑ bone mineral density of femur | [304] |
| Ovariectomy/inflammation rat model of senile osteoporosis | OLE •2.5–15 mg/Kg/day, enriched diet for 100 days |
↑ bone mineral density of femur; ↓ inflammatory biomarkers | [305] |
| Ovariectomy/inflammation rat model of senile osteoporosis | HTyr (0.017%) or Olive mill wastewater extract (0.08% or 0.0425%), enriched diet for 84 days |
↑ bone formation; ↑ bone mineral density of femur; ↓ oxidative stress | [306] |
| Ovariectomized rats as a model of osteoporosis Primary osteoblasts |
OLE •200 µg/Kg/dose for 12 weeks OLE •50–400 µg/mL for 24, 48, 72 h |
↑ bone mineral density of lumbar vertebra and left femur; ↓ IL-6 serum levels; ↓ lipid peroxydation; ↑ osteoblast proliferation; ↓ osteoclast differentiation |
[307] |
| H2O2-induced oxidative stress in the murine MC3T3-E1 osteoblast cell line | HTyr •5 µM |
↓ osteoblast apoptosis; ↓ ROS generation; ↑ ATP production and activities of mitochondrial complexes I, II, III and IV; ↓ mitochondrial morphological alterations ↓ OPA1 cleavage; ↑ activity of Akt/GSK3β signaling pathway | [308] |
| Sprague–Dawley rat model of unloading-induced muscle atrophy | Nutrient mix: HTyr (10 mg/Kg/day), R-lipoic acid (50 mg/Kg/day), acetyl-l-carnitine (100 mg/Kg/day), coenzyme Q10 (5 mg/Kg/day) •nutrient-enriched chow for 4 weeks |
↑ motor function; ↑ soleus muscle mass; ↓ protein degradation markers (MURF1, Atrogin-1, FOXO3); ↑ PGC1α; ↑ markers of mitochondrial biogenesis (Tfam, NRF1 expression, mitochondrial DNA copy number, complex I and II activities); ↓ mitochondrial morphological alterations; ↓ apoptosis (caspase-3 and -9 activity); ↑ total anti-oxidative capability, GSH content; ↓ oxidative stress (MAPK activity) |
[310] |
| Sprague–Dawley rats subjected to intensive exercise program for 8-weeks | HTyr •25 mg/Kg/day for 8 weeks via gavage |
↑ endurance capacity; ↓ protein degradation and autophagy markers (MURF1, Atrogin-1, Atg7, beclin-1, LC3); ↑ PGC1α expression and complex I and II activities; ↑ mitochondrial fusion and ↓ mitochondrial fission; ↑ oxidative stress markers (p53, p21 SOD2) | [313] |
| C2C12 myotubes treated with butylhydroperoxide to induce oxidative stress | HTyr-acetate •1–50 µM for 24 h |
↑ cell viability; ↓ OPA1 cleavage and mitochondrial morphology changes; ↑ ATP production and activities of mitochondrial complexes I, II and V; ↑ expression of MyHC | [314] |
| C2C12 myoblasts treated with H2O2 to induce oxidative stress | HTyr or HTyr-laurate •20 µM or 5 µM for 30 min |
↓ apoptosis | [105] |
| C2C12 myoblasts treated with TNFα to mimic inflammation-induced toxicity | HTyr •1–50 µM for 30 min |
↑ muscle creatine kinase activity; ↑ differentiation markers (MyHC and myogenin); ↑ mitochondrial biogenesis (PGC1α, complex I and II expression) |
[315] |
| Primary avian skeletal muscle cells | OLE •50 µM for 2 h |
↑ SIRT1, PGC1α; ↑ markers of mitochondrial biogenesis (Nrf1, Tfam, ATP5a1 expression and COX activity); ↓ mitochondrial ROS generation ↑ anti-oxidant markers (SOD2 and avUCP) | [316] |
| Primary avian skeletal muscle cells | OLE •50 µM for 2 h |
↑ SIRT1, PGC1α, ATP5a1, avUCP, SOD2; ↓ mitROS generation; ↑ Ca2+ channel TRPV1 activation and intracellular Ca2+ concentration; ↑ AMPK phosphorylation | [317] |
| C57BL/6 mice fed a high-fat diet | HTyr •10 mg/Kg/day or 50 mg/Kg/day for 17 weeks via gavage |
↓ body and organ weight; ↑ glucose tolerance ↓ serum levels of glucose, insulin, lipids and inflammatory cytokines; ↓ muscle lipid deposits (inhibition of SREBP pathway); ↑ antioxidant enzyme activity (GST); ↓ protein carboxylation and lipid oxidation ↓ mitochondrial fission (Drp1) and apoptotic markers (Bcl-2 family members and cleaved PARP); ↑ complex I, II and IV activities | [329] |
| db/db diabetic mouse model | HTyr •10 mg/Kg/day for 8 weeks via gavage |
↓ serum levels of glucose and lipids; ↓ protein and lipid damage mitochondrial complex I and IV activities | [329] |
| C2C12 myotubes | HTyr-acetate •25–75 µM for 12 h |
↑ glucose uptake | [330] |
| C57BL/6 mice fed a high-fat diet | OLE • high-fat diet containing 0.038% OLE for 12 weeks |
↓ fasting blood glucose; ↓ insulin resistance; ↑ GLUT4 expression and membrane localization in gastrocnemius muscle | [331] |
| C2C12 myotubes | OLE •1–100 µM for 60 min |
↑ GLUT4 translocation to membrane and glucose uptake; ↑ AMPK phosphorylation; ↓ palmitic acid-induced insulin resistance | [331] |
| C2C12 myotubes | OLE •200–400 µM for 24 h |
↑ glucose uptake and insulin sensitivity; ↑ AMPK and MAPK signalling; ↓ H2O2-induced ROS production and lipid peroxidation | [332] |
| Isolated soleus muscle incubated with palmitate | OLE •1.5 mM for 12 h |
↑ insulin-stimulated glucose uptake, GLUT4 membrane localization and AS160 phosphorylation; ↑ AMPK phosphorylation | [333] |
| Rat model of streptozotocin-induced diabetes | Olive leaf extract •512, 768 or 1024 mg/Kg/day (containing 20.3, 33 or 44.5 mg/Kg/day of OLE) for 10 days via i.p. injection |
↓ blood levels of glucose and triglycerides; ↑ soleus muscle fiber size; ↓ fibrosis in soleus muscle; ↑ GLUT4 translocation to the myofiber membrane and colocalization with the Rab GPTases Rab8A, Rab13 | [334] |
Abbreviations: Myosin heavy chain (MyHC), histone deacetylase-4 (HDAC4), muscle ring-finger protein-1 (MURF1), forkhead box O-3 (FOXO3), peroxisome proliferator-activated receptor coactivator 1α (PGC1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (Tfam), glucose transporter type 4 (GLUT4), manganese superoxide dismutase (SOD2), optic atrophy 1 (OPA1), tumor necrosis factor α (TNFα), cytochrome c oxidase-2 (COX-2), high-fat diet (HFD), sterol regulatory element-binding transcription factor (SREBP), dynamin-1-like protein (Drp1), cleaved poly(ADP-ribose) polymerase (PARP), B-cell lymphoma 2 (Bcl2), Akt substrate of 160 kDa (AS160), glutathione (GSH), glutathione S-transferase (GST), mitogen-activated protein kinase (MAPK), reactive oxygen species (ROS), avian-specific uncoupling protein (avUCP), transient receptor potential cation channel subfamily V member 1 (TRPV1), AMP-activated kinase (AMPK), silent mating type information regulation 2 homolog 1 (SIRT1), extra virgin olive oil (EVOO), glycogen synthase kinase 3 β (GSK3β).