Immunostimulation |
MET: |
- |
|
hyperinsulinemia and insulin-related pathways |
24, 25 |
|
regulation of inflammatory processes |
|
|
↑ energy stress, which leads to apoptosis of certain cancer cells |
46, 47 |
|
↓ of the Warburg effect |
24, 47, 48 |
|
inhibition of the mTORC1 pathway |
47 |
|
↑ caspases 3 and 7 |
25 |
|
↑ Bad and Bax expression |
|
|
↓ of Bcl-2 and Bcl-xl |
|
|
↓ of VEGF production |
|
|
↓ of cyclin D1 and E2F1 expression |
|
|
↓ of fatty acid synthesis in prostate cancer cells |
24,
47 |
|
anti-folate effect |
|
|
↑ P53 phosphorylation and its regulator, MDMX (indicating cell cycle
arrest) |
|
|
↑ cell resistance of lung adenocarcinoma without LKB1 after AMPK
restoration |
|
|
↓ of ROS production |
49 |
|
inhibition of tumor growth in obese and pre-diabetic rats |
|
|
↓ of TGF-β |
|
|
↓ epithelial-mesenchymal transition |
|
|
regulation of the expression of Notch receptors |
|
|
↓ viability of rho0 cancer cells (without mitochondrial DNA) |
50 |
|
↑ DNA methylation using S-adenosyl-methionine in breast cancer cells |
51 |
|
↑ sensitivity to chemotherapy in cancer stem cells |
25 |
|
↑ sensitivity to radiation therapy |
24 |
|
higher sensitivity of MET in cells with high Myc expression in cancer
suppression |
46 |
|
inhibition of M2 macrophage polarization and induction of change from
M2 to M1 polarization |
45 |
|
↓ the amount of myeloid suppressor cells and their migration to tumors |
|
|
↓ number of Treg lymphocytes |
|
|
↑ the amount of memory T lymphocytes |
|
Immunosuppression |
MET: |
- |
|
inhibition of monocyte differentiation into macrophages |
45 |
|
↓ infiltration of monocytes or macrophages in diseased tissues |
|
|
↑ anti-inflammatory T cells (like Th2, for example) or
immunosuppressive (Treg, for example) |
|
|
↓ inflammatory T cells (such as Th1 or Th17, for example) |
|
|
↓ of inflammatory cytokine expression and ↑ of anti-inflammatory
cytokines |
|
|
inhibition of function and ↓ number of neutrophils |
, 45,
52 |
|
improvement in B lymphocyte function and ↑ antibody production |
53 |
|
↓ of M1 macrophages and ↑ of M2 macrophages |
45, 54 |
|
suppression of phosphatase and tensin homolog (PTEN), a tumor
suppressor gene, in aortic smooth muscle cells |
55 |
|
↓ expression of messenger RNA from inflammatory cytokines (TNFα,
IL-1α, IL-1β and IL-6), chemokines and NF-κB |
52, 55, 56 |
|
↑ in the amount of Th2 or Treg lymphocytes and ↓ in the amount and
infiltration of Th1 and Th17 lymphocytes in diseased tissues |
56 |
|
↓ of autoantibodies in relevant models of autoimmune diseases |
|
|
↓ in the concentration of components associated with neutrophil
extracellular traps (NETs) |
57 |
Autophagy and Longevity |
MET: |
- |
|
↑ SIRT3 levels (associated with ↑ biogenesis, mitochondrial function,
↓ senescence of cardiomyocytes, etc.) |
58 |
|
↑ reverse transcriptase (hTERT) telomerase activity (associated with ↓
senescence in endothelial cells) |
|
|
↓ senescence markers: p16, p21, p27 and p53 |
|
|
↑ the β-oxidation regulatory protein, ACAD10, associated with ↑
nematode survival |
22 |
|
↑ in the expression of FGF21, a mitokine capable of improving the
lipid profile, glucose uptake, etc. |
59 |
|
PHEN: |
- |
|
↓ autophagy |
60 |
Mitochondrial and Associated Effects |
MET, PHEN: |
- |
|
↓ of the activity of mitochondria complex I and, therefore, of
oxidative phosphorylation |
21, 49 |
|
↓ in the production of ROS by complex I |
20, 21, 23, 49,
50 |
|
decrease in ROS production by SDH and mGPDH |
50 |
|
MET: |
- |
|
inhibition of mitochondrial glycerophosphate dehydrogenase (mGPDH) |
20, 50, 61 |
|
inhibition of ATP synthase and succinate dehydrogenase (SDH) |
50 |
|
activation of AMPK due to energy stress |
24, 25 |
|
inhibition of acetyl-CoA-carboxylase and ↓ expression of lipogenic
genes |
24 |
|
↓ gluconeogenesis in hepatocytes |
23-25 |
|
↓ oxidative stress and ↑ antioxidant defenses with long-term therapy |
58 |
|
improvement of superoxide desmutase levels in patients with DM2 |
52 |
Cardiovascular Effects |
MET: |
- |
|
protection against cerebral ischemia via nuclear factor related to
erythroid 2 (Nrf2) or inhibition of the NF-κB cascade |
62 |
|
recovery of post-stroke function and ischemia damage |
|
|
improvement of angiogenesis with chronic post-stroke treatment |
63 |
|
macrophage polarization to M2 with chronic post-stroke treatment |
|
|
↑ production of nitric oxide (NO) by means of nitric oxide synthase
endothelial (eNOS) in myocardial infarction (MI) |
64 |
|
stimulation of the adenosine receptor, increasing its synthesis,
decreasing reperfusion damage |
64, 65 |
|
inhibition of TLR4 signaling in MI (indicating ↓ of the production of
inflammatory mediators and left ventricular dysfunction) |
66 |
|
↓ cardiac remodeling, neutrophilic activity and myocardial injury in
MI with chronic pretreatment |
67 |