Table 1.
Summary of effects of the different natural agents on mitochondrial biogenesis.
| Substance | Model (cell or animals) | Result | References |
|---|---|---|---|
| Resveratrol | C57BL/6NIA mice | Resveratrol increased insulin sensitivity, AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor coactivator 1α (PGC-1α) receptor activity and improved mitochondrial number. Moreover, resveratrol improved motor function and reduced insulin-like growth factor-1 (IGF-1). These changes led to the improvement of health and survival of high-calorie diet mice. Therefore, resveratrol could be considered as a promising substance for the treatment of obesity-related disorders and diseases of aging. |
[38] |
| Resveratrol | C57Bl/6J mice | The administration of resveratrol protected mice against diet-induced obesity and insulin resistance by improving mitochondrial function and activating SIRT1 and PGC-1α. | [39] |
| Resveratrol | Endothelial cells | The mitochondrial biogenesis of endothelial cells was increased in presence of resveratrol by activating the PGC-1α/SIRT1 cascade. | [40] |
| Resveratrol | Transgenic rats | The administration of resveratrol for transgenic rats enhanced mitochondrial biogenesis and ameliorated Ang II-induced cardiac remodeling. | [41] |
| Resveratrol | C57BL/6J mice | Resveratrol activated AMPK and increased NAD+ in a SIRT1 dependent manner. This procedure led to the improvement of mitochondrial function. | [46] |
| Resveratrol | SIRT1 KO mice | Moderate doses of resveratrol improved mitochondrial function by SIRT1, which is required for AMPK activation. | [50] |
| Resveratrol | HepG2 cells | Resveratrol banded to the subunits of nicotinamide adenine dinucleotide (NADH) dehydrogenase to activate the mitochondrial complex I. | [51] |
| Resveratrol | C57BL/6J mice | Brain mitochondria of young mice were affected by resveratrol. This substance simulated complex I activity while the respiration rate was not improved. |
[52] |
| Resveratrol | Rat | The results demonstrated that resveratrol inhibited the function of complexes I to III of mitochondrial respiratory chain competing with coenzyme Q. | [53] |
| Resveratrol | C2C12 myoblasts, C3 cancer cells, and mouse embryonic fibroblasts | Resveratrol treatment improved cellular metabolism and growth and mitochondrial fusion. Moreover, cellular respiratory capacity and the activity of complexes I to IV have shown a surge after resveratrol treatment. | [54] |
| Resveratrol | Rat | Resveratrol had regulatory effects on the synthesis of ATP and complex V activity. | [55] |
| Resveratrol | Sprague-Dawley rats | Resveratrol demonstrated inhibitory effects on the enzymatic activity of both rat brain and liver F0F1-ATPase/ATP synthase. | [56] |
| Resveratrol | Human fibroblasts | The resveratrol treatment excessed primary oxygen intake rates and ATP formation on human fibroblasts derived from the skin of patients. | [57] |
| Resveratrol | Human skin fibroblasts | Resveratrol improved mitochondrial biogenesis using SIRT1- and AMPK-independent pathways. This improvement involved the estrogen receptor (ER) and estrogen-related receptor alpha (ERRα) signaling pathway. |
[58] |
| Resveratrol | Complex I-deficient human fibroblasts | Resveratrol treatment reduced oxidative stress in mitochondrial complex I deficiency using SIRT3. The growth in SIRT3 creativity led to dramatic decreases in ROS level and enhancement of SOD2. | [60] |
| Resveratrol | Bhas 42 cells | Resveratrol enhanced mitochondrial content by protecting against benzo [a] pyrene-induced bioenergetic dysfunction and ROS generation in neoplastic transformation model. | [61] |
| Quercetin | ICR mice | The administration of quercetin elevated mitochondrial biogenesis and exercise tolerance in the brain and muscle. | [63] |
| Quercetin | Young adult male | The administration of quercetin increases mtDNA numbers and improved mitochondrial biogenesis that led to enhanced physical performance. | [64] |
| Quercetin | HepG2 cells | Administration of quercetin increased the mitochondrial DNA content and biogenesis by activating HO-1 in HepG2 cells. | [65] |
| Quercetin | Obese mice | Administration of quercetin had protective effects on traumatic brain injury of obese mice by regulation of the NRF-2/HO-1/PGC-1α signaling pathway. | [67] |
| Quercetin | Rat | After induction of hypobaric hypoxia in the rat hippocampus, the administration of quercetin led to increased levels of mitochondrial DNA, TFAM, PGC-1α, and NRF-1. | [68] |
| Quercetin | Rodent | The functions of complexes II, IV, and V were elected after the administration of quercetin. Moreover, this substance improved ATP levels, which could affect the activity of OXPHOS. The provocation of mitochondrial biogenesis in presence of quercetin was occurred due to the activation of the PGC-1α/NRF-1-NRF-2-TFAM cascade. |
[69] |
| Quercetin | Male C57BL/6 mice | Quercetin enhanced hepatic mitochondrial oxidative metabolism by inducing heme oxygenase-1 via the Nrf-2 pathway. | [70] |
| Quercetin | Neuronal cell | Quercetin reduced ischemic neuronal cell death by preserving mitochondrial spare respiratory capacity. Moreover, this substance completely blocked neuroprotection by oxide synthase. | [71] |
| Quercetin | Wistar rats | The combination of oral quercetin supplementation and exercise prevents brain mitochondrial biogenesis. | [75] |
| Quercetin | Male C57BL/6 mice | Exercise, but not quercetin, ameliorates inflammation, mitochondrial biogenesis, and lipid metabolism in skeletal muscle after strenuous exercise by high-fat diet mice. | [76] |
| Quercetin | C57BL/6J mice | Quercetin increased skeletal muscle mitochondrial number and function. | [77] |
| Quercetin | OA rat model | The administration of quercetin in OA rats reduced ROS levels and ameliorated mitochondrial damages which led to the preservation of the integrity of the extracellular matrix of joint cartilage. This procedure might involve the regulation of the AMPK/SIRT1 signaling pathway. | [79] |
| Hydroxytyrosol | Retinal pigment epithelial cells | As shown in the retinal pigment epithelial cells, hydroxytyrosol deacetylated through SIRT1 and activated PGC-1α, which promoted mitochondrial biogenesis. | [81] |
| Hydroxytyrosol | Rat | The administration of hydroxytyrosol regulated the expression of mitochondrial complexes I and II in skeletal muscle by the PGC-1α signaling pathway. | [82] |
| Hydroxytyrosol | Murine 3T3-L1 adipocytes | The administration of hydroxytyrosol improved protein expression and function of mitochondrial complexes I, II, III, and V. | [83] |
| Hydroxytyrosol | Human fibroblasts | Hydroxytyrosol increased the phosphorylation of PKA and CREB, which regulated the biogenesis of OXPHOS. | [84] |
| Hydroxytyrosol | Endothelial cells | Hydroxytyrosol stimulated PGC-1α expression, which led to NRF-1 and TFAM stimulation, the elevation of mitochondrial DNA content, and ATP synthesis. | [85] |
| Isoflavones (daidzein, genistein, and formononetin) | Rabbits' proximal renal tubular cells | Rabbit's proximal renal tubular cells in exposer to daidzein, genistein, and formononetin had shown elevated mitochondrial biogenesis through the PGC-1α/SIRT1 pathway. | [86] |
| Flavones (wogonin and baicalein) | Rats' L6 skeletal muscle cells | Antimycin A-induced mitochondrial dysfunction of rat L6 cells was ameliorated by Scutellaria baicalensis extracts. | [87] |
| Flavan-3-ol | Skin fibroblasts from Down's syndrome patients | Epigallocatechin-3-gallate prevents oxidative phosphorylation deficit and promotes mitochondrial biogenesis in human cells from subjects with Down's syndrome. | [88] |
| Green tea's polyphenols | Rats | Green tea elevated mtDNA contact, mRNA, and proteins of TFAM, PGC-1α, and complex IV in mitochondria. | [89] |
| Epicatechin-rich cocoa | Patients with type 2 diabetes | The expressions of SIRT1 and PGC-1α were enhanced in T2D human patients after administration of epicatechin-rich cocoa. This enhancement led to the improvement of mitochondrial biogenesis in skeletal muscle. | [90] |
| Curcumin | Mice | The mitochondrial membrane potential (MMP) and ATP contents in the brain of fast-aging augmented senescence-8 mice were increased due to the enhancement of PGC-1α protein expression in presence of curcumin. | [92] |
| Curcumin | Mice | The administration of curcumin supplementation elevated the levels of PGC-1α, TFAM, ATP, and levels of mitochondrial respiratory complexes in the APO3-mutant mice's brain. | [93] |
| Yerba mate | Obese mice | C2C12 cells were showed increased mitochondrial respiratory capacity and DNA content in presence of yerba mate. Moreover, in the obese mice, this substance increased mtDNA levels in brown adipose tissue and skeletal muscle. These effects were related to the AMPK/SIRT1/PGC-1α-mediated cascade in presence of yerba mate. |
[94] |
| Curcumin | Rat skeletal muscle | The increasing of cAMP levels, mtDNA amounts, SIRT1 expression, PGC-1α deacetylation, AMPK phosphorylation, and NAD+/NADH ratio was observed due to the curcumin treatment on skeletal muscle. | [95] |
| Epigallocatechin-3-gallate (EGCG) | Obese mice | EGCG modulated the biogenesis of mitochondrial and brown adipose tissue thermogenesis through AMPK triggering in brown adipose tissue and stimulating the mitochondria DNA replication. | [96] |
| Epigallocatechin gallate (EGCG) | Hepa1-6 cells | The amounts of the cytochrome C, oxygen consumption, ATP synthesis, and NAD+/NADH ratio were increased by modified EGCG derivatives in Hepa1-6 cells. | [98] |
| Procyanidins | Mice | The expression of the PGC-1α gene and copy number of DNA were increased after oral administration of apple procyanidin in OA models of mice. | [99] |
| Digitoflavone | PC12 cells | Mitochondrial biogenesis improved in presence of digitoflavone by regulation of AMPK and increasing of antioxidant capacity of cells. | [100] |
| Anthocyanins | 3T3-L1 preadipocytes | Anthocyanin inhibited adipocyte differentiation through activation of the AMPK signaling pathway. | [101] |
| Cyanidin-3-glucoside | 3T3-L1 preadipocytes | The intracellular levels of CAMP were signification increased in preadipocytes after Cy36 exposure. | [102] |
| Anthocyanins | 3T3-L1 preadipocytes | The lipogenesis stage during adipocyte differentiation of 3T3-L1 preadipocytes was inhibited by anthocyanins. This substance regulated BAT's function through AKT and ERK signaling pathways. | [103] |
| Mulberry anthocyanins, cyanidin 3-glucoside, and cyanidin 3-rutinoside, | BAT-cMyc cell | Mulberry anthocyanins, cyanidin 3-glucoside, and cyanidin 3-rutinoside increase the number of mitochondria during brown adipogenesis. | [104] |
| Mulberry and mulberry wine | C3H10T1/2 mesenchymal stem cell | The number and function of mitochondria were increased during brown adipogenesis by exposure to the mulberry and mulberry wine. | [105] |
| Rutin | Mice | The administration of rutin decreased the blood levels of lactic acid in the forced swimming mouse model. Moreover, in these animals, the levels of malondialdehyde (MDA) were decreased in the muscle and brain. In these tissues, regulation of SOD and GPx increased PGC-1α and sirtuin 1 (SIRT1). The antioxidative effects of this flavonoid were also observed in the brain of mice by regulation of TPI, GDI, and CB1. | [107] |
| Glycyrrhizic acid | Mice | Glycyrrhizic acid (GA) had neuroprotective effects and increased memory and antioxidant-related enzymes. | [108] |
| Glycyrrhizic acid | PC12 cells | Mitochondrial function and biogenesis were enhanced against aluminum toxicity of PC12 cells by glycyrrhizic acid treatment. | [109] |
| Glycyrrhizic acid | Renal tubular epithelial cell | The high glucose-related renal tubular epithelial cell injury was ameliorated by glycyrrhizic acid treatment. | [110] |
| Glycyrrhizic acid | Human coronary artery endothelial cell | Mitochondria regulation due to the glycyrrhizic acid protective effects ameliorated hypoxia/reoxygenation-induced human coronary artery endothelial cell damage. | [111] |
| Citrus tangeretin | Kunming mice and C2C12 myoblasts | Mitochondrial biogenesis in skeletal muscle was improved by activation of the AMPK-PGC1-α pathway in presence of citrus. | [112] |
| Cyanidin-3-glucoside | Human hepatocyte cell | The treatment of hepatocyte cell line by cyanidin-3-glucoside showed the upregulation of PGC-1α and SIRT 1 expression in a dose- and time-dependent manner. Moreover, the expression of NRF1 and TFAM was increased which led to improvement of function and biogenesis of mitochondria. |
[113] |
| Isorhamnetin | 3T3-L1 cells | The expression of mitochondrial genes, activating AMPK, and replicating of mtDNA in presence of isorhamnetin led to antiobesity effects through the regulation of mitochondrial biogenesis. | [114] |
| Nobiletin | C57BL/6 mice | The activation of SIRT-1/FOXO3a-medicated autophagy and mitochondrial biogenesis in presence of nobiletin ameliorated hepatic ischemia and reperfusion. | [115] |
| Eriocitrin | HepG2 cells | The oral administration of eriocitrin upregulated the levels of cytochrome c, oxidase subunit 4, TFAM, NRF1, and ATP synthase, which improved liver function in contribution to the mitochondrial biogenesis. | [120] |
| Polymethoxy flavonoids (black ginger extract) | C2C12 myoblasts | The black ginger's flavonoids including 5-hydroxy-7-methoxyflavone, 5-hydroxy-3,7,40-trimethoxyflavone, and 5,7-dimethoxyflavone enhanced ATP production on C2C12 myoblasts through regulation of PGC-1α and AMPK pathway. | [121] |
| Polymethoxylated flavone (sudachitin) | C57BL/6J mice | Sudachitin improved the SIRT 1 and PGC-1α, which caused the amelioration of metabolic disorders and dyslipidemia through improving mitochondrial biogenesis. | [122] |
| Chikusetsu saponin | Neuroblastoma cells | Chikusetsu saponin has plummeted the oxidative hazard in neuroblastoma cells that had been exposed to H2O2 through the elevation of PGC1a and SIRT-1 activation. | [123] |
| Platycodon grandiflorum | Brown adipose cells | The ethanolic extract of Platycodon grandiflorum upregulated the mitochondrial genes such as PGC1α, SIRT3, and Nrf, which has exhibited beneficial effects in brown adipose. | [124] |
| Amla | C2C12 myotubes | The protective effects of amla in myotubes subjected to tBHP have been observed in the context of mitochondrial function and biogenesis. The activation of AMPK and Nrf signaling in C2C12 myotubes cells has been attributed to these protective effects. | [125] |