Oxidative Medicine and Cellular Longevity

Oxidative Medicine and Cellular Longevity / 2020 / Article

Research Article | Open Access

Volume 2020 |Article ID 5232614 | https://doi.org/10.1155/2020/5232614

Jian-Kang Mu, Yan-Qin Li, Ting-Ting Shi, Li-Ping Yu, Ya-Qin Yang, Wen Gu, Jing-Ping Li, Jie Yu, Xing-Xin Yang, "Remedying the Mitochondria to Cure Human Diseases by Natural Products", Oxidative Medicine and Cellular Longevity, vol. 2020, Article ID 5232614, 18 pages, 2020. https://doi.org/10.1155/2020/5232614

Remedying the Mitochondria to Cure Human Diseases by Natural Products

Academic Editor: Ratanesh K. Seth
Received04 Apr 2020
Revised05 Jun 2020
Accepted25 Jun 2020
Published14 Jul 2020

Abstract

Mitochondria are the ‘engine’ of cells. Mitochondrial dysfunction is an important mechanism in many human diseases. Many natural products could remedy the mitochondria to alleviate mitochondria-involved diseases. In this review, we summarized the current knowledge of the relationship between the mitochondria and human diseases and the regulation of natural products to the mitochondria. We proposed that the development of mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represents an attractive strategy for a mitochondria-involved disorder therapy. Moreover, investigating the mitochondrial regulation of natural products can potentiate the in-depth comprehension of the mechanism of action of natural products.

1. Introduction

As an important organelle in the cells, the mitochondria are considered the main powerhouse of the cells, because they can apply glucose, fatty acids, and certain amino acids as fuel sources to produce ATP through oxidative phosphorylation [1]. The mitochondria also play a critical role in many other processes, such as reactive oxygen species generation, maintenance of calcium homeostasis, adjustment of apoptotic cell death, regulation of lipid metabolism, and autophagy [2]. Thus, mitochondrial dysregulation of any form may lead to a variety of human diseases [2]. Mitochondrial dysfunction has been implicated in neurodegenerative disorders, cancer, liver diseases, myocardial injury, diabetes, and obesity [3, 4].

Natural products, including mixture and monomer, have been widely used to treat mitochondria-related diseases and have been reported as a highly significant source for the exploration of promising drugs/nutrients that have led to novel compounds for alleviating mitochondria-involved disorders, such as compounds with antitumor, neuroprotective, cardioprotective, hepaticprotective, antidiabetes, and antiobesity agents. The chemical synthesis of new drugs has rapidly developed in recent years with the advancement of combinatorial chemistry and computer-aided drug design technology [5]. However, due to the novel structures, therapeutic abilities, and certain unique pharmacological effects of the chemicals in natural products, the exploration of drugs and lead compounds from natural products is still an important approach for drug development [6].

The focus of this review was on mitochondrial regulation with natural products to treat human diseases. The purpose of this review was to examine the current knowledge of the relationship between mitochondria and human diseases and the regulation of natural products to the mitochondria. We proposed that the development of mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represented attractive strategies for treating mitochondria-involved disorders. Moreover, investigating mitochondrial regulation of natural products can potentiate the in-depth comprehension of the underlying mechanism of action of natural products.

2. Remedying the Mitochondria to Cure Human Diseases by Natural Products

2.1. Regulating the Mitochondria to against Cancer

Prevention of cell death is a hallmark of human cancers and a major cause of treatment failure [7]. The mitochondria control the activation of apoptotic effects or mechanisms by regulating the translocation of proapoptotic proteins from the mitochondrial intermembrane space to the cytosol [8]. In addition, the mitochondria play an important role in various forms of nonapoptotic cell death and, especially, in necroptosis [7]. Because of their role in the regulation of basic cellular functions, it is not surprising that the mitochondria are involved in many aspects of tumorigenesis and tumor progression. For example, mutations in mitochondrial DNA that affect the compositions of the mitochondrial respiratory chain will lead to ROS overproduction, inefficient ATP production, and oxidative damage to the mitochondria and other macromolecules (including DNA), thus favoring chromosomal instability and carcinogenesis [9]. Furthermore, extensive polymorphisms and mutations in the mitochondrial DNA correlated with an increased risk of developing various malignancies [10]. Therefore, inducing cancer cells to undergo mitochondrial lesions and loss of function has become a very important direction in the field of anticancer drugs.

A large number of studies have shown that natural products have a significant anticancer activity by regulating the mitochondrial function with the following main mechanisms (Table 1): (1) promote the release of proapoptotic factors and induce tumor cell apoptosis by changes in mitochondrial membrane permeability, regulation of Bcl-2 family proteins, and other pathways; (2) regulate the mitochondrial energy metabolism, including the respiratory chain and tricarboxylic acid cycle; and (3) increase ROS levels and enhances oxidative damage.


Types of nature productsNatural productsMitochondrial regulationTypes of cancersExperimental models

MixtureBulbine frutescens [37]Cell cycle arrest, ROS production, apoptosis induction, disruption of ΔΨmTriple negative and luminal breast cancerHuman breast cancer cells (MDA-MB-231 and T47D) and human embryonic kidney 293 (HEK293) cells
Bullfrog oil [38]Increases intracellular ROS levels, maintains DNA integrity, and reduces ΔΨmMelanomaHuman melanoma cells A2058

MonomerRhein [39]Inhibits mitochondrial energy metabolism, decreases cellular ATP and ADP levels, changes the ratio of ATP to ADP, and induces mPTP openingLiver cancerLiver cancer cell lines (SMMC-7721 and SMMC-7721/DOX)
Orientin [40]Increases of intracellular ROS levels in HT29 cells in a dose-dependent manner, modulates Bcl-2 family proteins, induces mitochondrial cytochrome c release into the cytoplasm in a concentration-dependent mannerHuman colorectal carcinomaColorectal carcinoma cells (HT29)
Licochalcone A [41]Increases the ratio of Bax/Bcl-2 and reduces the integrity of the mitochondria and promotes the release of cytochromes from mitochondria to the cytoplasmBladder cancerHuman bladder cancer cells (T24 and 5637)
Asparanin A [42]Induces apoptosis through the mitochondrial pathway, including the deregulation of Bak/Bcl-xl ratio, which leads to the generation of ROS, upregulation of cytochrome c followed by decrease of ΔΨm, and activation of caspasesEndometrial cancerEndometrial cancer cell line Ishikawa
Parameritannin A-2 [43]The combination of doxorubicin and parameritannin A-2 remarkably increases the release of cytochrome c and the activation of caspase-3 and caspase-9Gastric cancerHGC27 cells
Gracillin [44]Attenuates mitochondria-mediated cellular bioenergetics by suppressing ATP synthesis and producing ROSLung cancerH1299, H460, and A549 cells
Cernumidine [45]The combination of cernumidine and cisplatin downregulates Bcl-2 and upregulates proapoptotic Bax and depletion of the ΔΨm.Bladder cancerRT4, T24, and 5637 cells

2.2. Regulating the Mitochondria to against Neurodegenerative Diseases

Neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and Friedreich’s ataxia, are strongly age related and currently cannot be cured [11]. In neurons, efficient clearance of injured mitochondria through mitophagy plays a fundamental role in mitochondrial and metabolic homeostases and neuronal survival and health [11]. The mitochondria are organized in a highly dynamic tubular network that is continuously reshaped by opposing processes of fusion and fission [12]. Defects in fusion or fission will result in mitochondrial fragmentation, reduce energy metabolism, and increase oxidative stress, thus accelerating cell dysfunction and death, leading to neurodegenerative disease [13]. Therefore, the regulation of mitochondrial dynamics, such as fusion, fission, and mitochondrial phagocytosis, represents a significant avenue for controlling the fate of neurons [12, 13].

Through numerous animal experiments and clinical studies, a variety of drugs from natural products were identified with neuroprotective effects. Many of these drugs can exert neuroprotective effects by protecting the mitochondrial function (Table 2): (1) regulate ΔΨm and membrane fluidity; (2) protect mitochondrial structure and morphology; (3) regulate mitochondrial apoptotic pathways, reduce the release of proapoptotic factors, and inhibit neuronal apoptosis; (4) improve the cellular mitochondrial respiratory function (energy metabolism); (5) enhance superoxide dismutase (SOD) activity, inhibit oxidative stress, and reduce ROS damage; and (6) improve mitophagy.


Types of nature productsNatural productsMitochondrial regulationTypes of diseasesExperimental models

MixtureSolanum melongena extract [46]Prevents apoptosis, reduces SOD, and increases ATP production and upregulates SOD and catalase activityRotenone-induced neurotoxicityRotenone-induced neurotoxicity in PC-12 cells
Ganoderma lucidum [47]Regulates ΔΨm, radical oxygen species accumulation, and ATP depletion and activates the AMPK/mTOR and Pink1/Parkin signaling pathwaysParkinson’s diseaseMPTP- (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine-) induced mouse model

MonomerLinalool [48]Reduces mitochondrial ROS and calcium levels and maintains ΔΨm to reduce oxidative stressGlutamate-induced nerve injuryGlutamate-induced mitochondrial oxidative stress in immortalized neuronal HT-22 cells
Cinnamic acid derivatives [49]Blocks apoptosis and protects mitochondrial physiological functionsNeuroprotection and angiogenesisH2O2-induced injury model in HBMEC-2 and SH-SY5Y cells
Proanthocyanidins [50]Inhibits signaling pathways involved in mitochondrial-mediated apoptosisMethyl mercuric chloride-induced neurotoxicityCortical neuron cells from rats
α-Arbutin [51]Reduces oxidative stress, stabilizes ΔΨm, and enhances adenosine triphosphateParkinson’s diseaseRotenone-treated human neuroblastoma cells (SH-SY5Y) and drosophila Parkinson’s disease model
Naringenin [52]Reduces oxidative load, which in turn maintains mitochondrial function and prevent neuronal cell deathH2O2-induced neurotoxicityHuman neuroblastoma SH-SY5Y cells
Apigenin [53]Reduces oxidative stress, downregulates the TLR4/NF-κB signaling pathway, and inhibits mitochondrial-mediated neuronal apoptosisAcrylonitrile-induced neuroinflammationAcrylonitrile-induced neurotoxicity in rats
Auraptene [54]Enhances mitochondrial respiration and attenuates ROS productionParkinson’s disease-like behaviorRotenone-treated SN4741 cells
Naringenin [55]Inhibits HO-induced mitochondrial dysfunction, including a decrease in membrane potential and Bcl-2/Bax ratio, cytochrome c release, and caspase-3 cleavageH2O2-induced neurotoxicityHuman neuroblastoma SH-SY5Y cells
Ulmoside A [56]Induction of translocation of cytochrome-c, decrease of Bcl-2 level, increase of Bax level, and cleavage of caspase-3 in neuronal cellsLipopolysaccharides- (LPS-) induced neurotoxicityLPS-treated mouse neuroblastoma N2A cell line
Celastrol [57]Inhibits apoptosis of dopaminergic neurons by activating mitosis and degrading damaged mitochondriaParkinson’s disease1-Methyl-4-phenylpyridinium- (MPP+-) induced SH-SY5Y cell model and MPTP-induced mouse model

2.3. Regulating the Mitochondria to Remedy Liver Diseases

The liver, an organ with high energy requirements, plays a pivotal role in the synthesis and secretion of multiple endogenous compounds. Liver functioning is highly dependent on the mitochondria producing ATP for biosynthetic and detoxifying properties [14]. In previous studies, it was suggested that mitochondrial dysfunction is a critical factor in the initiation and progression of liver diseases, including ischemia/reperfusion (IR) injury, nonalcoholic/alcoholic fatty liver disease (NAFLD/AFLD), nonalcoholic/alcoholic steatohepatitis (NASH/ASH), and hepatic fibrosis, as well as intoxications by xenobiotics or heavy metals, bacterial, viral, and parasitic infections [15]. The mitochondria play an important role in the process of hepatic apoptosis and necrosis. The degree of the mitochondrial activity in the liver directly affects liver function [16].

In previous studies, it was shown that some natural medicines can protect liver cells from damage or liver fibrosis by protecting the mitochondrial function (Table 3): (1) stabilize the fluidity of mitochondrial membranes and protect the structure and morphology of liver mitochondria; (2) regulate the mitochondrial apoptotic pathway, reduce the release of proapoptotic factors, and inhibit hepatocyte apoptosis; (3) increase the mitochondrial energy metabolism; and (4) enhance SOD activity, inhibit oxidative stress, and reduce ROS damage.


Types of nature productsNatural productsMitochondrial regulationTypes of liver diseasesExperimental models

MixtureRooibos tea [58]Enhances the ability of the respiratory chain and energy productionLiver injuryCarbon tetrachloride- (CCl4-) induced liver damage in rats
Cimicifuga racemosa extract [59]Maintains mitochondrial integrity and ATP levels; prevents mitochondrial ROS formation, loss of ΔΨm, and cell death; and mediates a switch from mitochondrial respiration to glycolysisLiver injuryErastin-treated HT22 cells and ras-selective lethal compound c-treated HepG2 cells
Sipjeondaebo-tang [60]Improves oxidative stress and regulate ΔΨmLiver injuryIron/arachidonic acid-treated HepG2 and CCl4-induced acute liver injury in mice
Polygonatum kingianum [61]Inhibits the reduction of SOD, GSH, ATP synthase, and complex I and II, in the mitochondria; upregulates and downregulates mRNA expression of carnitine palmitoyl transferase-1 and uncoupling protein-2, respectively; inhibits the increase of caspase-9, caspase-3 and Bax expression in hepatocytes; and decreases the expression of Bcl-2 in hepatocytes and cytchrome c in the mitochondriaNAFLDHigh-fat diet-induced NAFLD in rats
Punica granatum L. [62]Decreases the expression of uncoupling protein 2 (UCP2), restores the ATP content, inhibits mitochondrial protein oxidation, and improves mitochondrial complex activity in the liverNAFLDHigh fat diet-induced NAFLD in rats and ellagic acid treated HepG2 cells

MonomerBetaine [63]Enhances mitochondrial function by increasing mitochondrial fusion and improves cell survivalLiver injuryOligomycin-/rotenone-treated human HCC (Huh7) cells
Nicotinamide riboside [64]Enhances Sirt1 and PGC-1α activity, reduces oxidative stress, and restores mitochondrial biogenesis and aerobic respirationAFLDEthanol-induced AFLD in C57BL/6J mice and ethanol-treated HepG2 cells
Puerarin [65]Improves liver complex I and complex II activity and regulates mitochondrial DNA contentNAFLDHigh-fat and sucrose diet-induced NAFLD in C57BL/6J mice
Diosgenin [66]Improves oxidative stress and increases ΔΨmNAFLDPalmitic acid-induced NAFLD in L-02 cells
Silybin [67]Stimulates mitochondrial fatty acid oxidation, reduces basal and maximal respiration and ATP production in steatohepatitis cells, and rescues fatty acid-induced apoptotic signals and oxidative stress in steatohepatitis cellsNAFLD/NASHOleate/palmitate mixture and TNFα-treated rat hepatoma FaO cells
Salvianolic acid B [68]Decreases cytochrome c and caspase-3 protein expression, increases mfn2 mRNA expression and ΔΨm, and enhances mitochondrial respiratory functionNASHHigh-fat diet-induced NASH in rats
NecroX-7 [69]Reduces mitochondrial ROS and intracellular ROS/RNS levels, protects ΔΨm, improves abnormal mitochondrial morphology, and reduces steatosis and oxidative damage by inhibiting mitochondrial ROS/reactive nitrogen species (RNS)NASHLeptin-deficient ob/ob and methionine/choline-deficient diet-fed ob/ob mice

2.4. Regulating the Mitochondria to against Diabetes and Its Complications

Diabetes mellitus (DM) is one of the most common metabolic diseases worldwide [17]. Patients with DM display hyperglycemia induced by a damage in insulin secretion (type 1), insulin action (type 2), or both. Type 1 diabetes mellitus (T1DM), which accounts for less than 10% of diabetes cases, is characterized by an immune-mediated destruction of β cells in the pancreatic islets of Langerhans, resulting in insulin deficiency [18]. Type 2 diabetes mellitus (T2DM), which accounts for less than 90% of diabetes cases, involves insulin resistance (IR) in peripheral tissues and increased levels of blood glucose, because of overnutrition with an insulin secretion defect [18, 19]. IR continuously exists in the development of T2DM. A defect in the secretion function of pancreatic beta-cell is the prerequisite of T2DM development [20]. Mitochondrial dysfunction is the common mechanism of IR and injury of secretion function of pancreatic beta-cell [20, 21]. Furthermore, many mitochondrial gene mutation sites related to diabetes have been found, and the 3243A → G mutation in the mtDNA tRNALeu(UUR) gene is the most common cause of mitochondrial diabetes [22]. This mutation results in the reduction of insulin release and insulin resistance and leads to persistent hyperglycemia, which in turn causes mitochondrial dysfunction and reduces insulin release [22]. Muscle biopsies of diabetic patients have revealed abnormal mitochondrial metabolism and reduced mitochondria quantity [23, 24].

A large proportion of the diabetic population develops chronic vascular complications leading to significant morbidity and mortality [25]. Microvascular complications include diabetic nephropathy, neuropathy, and retinopathy; muscle atrophy, coronary, and peripheral vascular diseases; and stroke [25]. The hyperglycemic milieu alters the epigenetic machinery and mtDNA. Other genes associated with mitochondrial homeostasis are epigenetically modified, thereby further contributing to mitochondrial damage [26]. Dysfunction is seen in the context of an altered mitochondrial metabolism and oxygen consumption, increased oxidative stress, and alterations to mitochondrial networking and turnover. An increasing body of evidence has highlighted the role of mitochondrial dysfunction in the development of diabetic complications [27, 28].

In previous studies, it was found that many natural products alleviated the symptoms of T2DM and its complications by protecting the mitochondrial function (Tables 4 and 5): (1) protecting the structure and morphology of the mitochondria from pathological organs/tissues; (2) regulating the mitochondrial apoptotic pathway, reducing the release of proapoptotic factors, and inhibiting cell apoptosis; (3) increasing mitochondrial energy metabolism; and (4) enhancing SOD activity, inhibiting oxidative stress, and reducing ROS damage.


Types of nature productsNatural productsMitochondrial regulationExperimental models

MixturePolysaccharides from Portulaca oleracea L. [70]Improves ΔΨm, increases ATP production, depolarizes cell membrane potential, and increases intracellular Ca2+ levelsTetrodotoxin-treated INS-1 cells
Korean red ginseng [71]Increases mtDNA copy number of mitochondrial biogenesis-related transcription factors (PGC-1α and T-fam)C57BL/KsJ db/db mice (a genetic animal model of obese T2DM)

MonomerBerberine [72]Reduces mitochondrial ROS levels primarily through Sirt3 modificationArsenic-induced Sirt3 modifications in isolated mitochondria from rat pancreas
Quercetin [73]Reduces ROS, increases complex I activity and electron transfer system coupling efficiency, increases cellular NAD/NADH ratio, and activates the PGC-1α mediated pathwayHigh-glucose-stimulated HepG2 cells
Theaflavins [74]Enhances the mitochondrial DNA copy number, downregulates the PGC-1 β mRNA level, and increases PRC mRNA expressionPalmitic acid-induced I/R in HepG2 cells
Silibinin [75]Improves mitochondrial quality, regulates ΔΨm, and increases the Bcl-2/Bax ratioPalmitic acid-induced apoptosis and mitochondrial dysfunction in pancreatic INS-1 cells
Puerarin [76]Improves the tricarboxylic acid cycle and oxidative phosphorylation function of the mitochondria of skeletal muscle, enhances the expression levels of regulators of mitochondrial biogenesis (Sirt 1 and PGC-1α), and increases the density of the mitochondriaHigh-fat diet-/streptozocin-induced diabetic rats and palmitate acid-treated rat L6 skeletal muscle cells


Types of nature productNatural productsMitochondrial regulationCured complicationsExperimental models

MixtureQiDiTangShen granules [77]Improves mitochondrial quality and increases the expression of Sirt1 and the proportion of p-AMPK (thr172)/AMPKNephropathydb/db mice
Shengmai San [78]Increases protein levels of complexes I, III, and V and regulates the activity of oxidative phosphorylation complexes I and IVCardiomyopathyLeptin receptor-deficient db/db mouse and palmitate acid-treated H9C2 cells
Water extracts of Liuwei Dihuang [79]Improves ΔΨm and inhibits NADPH oxidase activation, and ROS productionMuscle atrophyMethylglyox-treated C2C12 myotubes and streptozocin-treated C57BL/6 mice

MonomerAnthocyanins [80]Inhibits the generation of ROS, cellular apoptosis, expression of cleaved caspase-3 and the Bax/Bcl-2 ratio and enhances the expression of cytochrome c released from mitochondriaNephropathyBKS db/db c57BL6 mice and high-glucose-stimulated HK-2 cells
Orientin [81]Regulates ΔΨm and the activation of mitophagyNephropathyHigh-glucose-treated MPC-5 cells
Salidroside [82]Increases mitochondrial DNA copy and electron transport chain proteins and improves the reduction of Sirt1 and PGC-1α expressionNephropathyStreptozotocin-induced diabetic nephropathy in obese mice
Astragalus polysaccharides [83]Inhibits the expression of proapoptotic proteins of both the extrinsic and intrinsic pathways and modulates the ratio of Bcl-2 to Bax in the mitochondriaCardiomyopathyHigh-glucose-stimulated H9C2 cells
Ginsenoside Rb1 [84]Reduces mitochondrial damage and activates oxygen production, enhances the Bcl-2/Bax ratio, and inhibits the expression of cleaved caspase-3 and cleaved caspase-9EncephalopathyMethylglyoxal-induced damage in SH-SY5Y cells
Hydroxytyrosol [85]Increases mitochondrial complex IV and HO-1 expression through activating the AMPK pathway, followed by preventing the high-glucose-induced production of ROS and reduces cell viabilityNeuropathyMale db/db C57BL/6J mice and SH-SY-5Y neuroblastoma cells

2.5. Regulating the Mitochondria to Antiobesity

Obesity is caused by an imbalance between energy intake and expenditure and results in excessive energy that in adipose tissue is stored as triglycerides (TGs) [29]. It is not only recognized as a simple condition but also causes many metabolic diseases, such as cardiovascular disease, T2DM, hypertension, and fatty liver disease [30]. In many organs and tissues (including adipose tissue), the mitochondria are center stage in the control of energy homeostasis. Research evidence indicates that mitochondrial dysfunction in adipocytes is closely related to obesity [31]. Various physiological conditions, such as excessive nutrition and genetic factors, disrupt mitochondrial function by impairing mitochondrial biogenesis, dynamics, and oxidative capacity. Mitochondrial dysfunction in adipocytes may have impact on adipogenesis and insulin sensitivity and may significantly alter their metabolic function, which ultimately leads to obesity [32].

Animal experiments and clinical studies have successively identified many drugs from natural products for treating obesity. Many of these drugs can regulate mitochondrial function to treat obesity, primarily through promoting energy and fat metabolism (Table 6).


Types of nature productsNatural productsMitochondrial regulationExperimental models

MixtureGreen tea [86]Moderates CPT-1 and ACAA2 levels and reduces CPT-2 and ACAD levelsHigh-fat diet-induced obese in C57BL/6 mice
Peanut sprout extracts [87]Promotes mitochondrial fatty acid oxidationDibutyryl cyclic adenosine monophosphate- (cAMP-) stimulated 3T3-L1 cells and rosiglitazone-stimulated C3H10T1/2 cells
Melinjo (Gnetum gnemon L.) seed extract [88]Upregulates thermogenic uncoupling protein 1 (UCP1) and mitochondrial marker cytochrome c oxidase subunit IV protein expression in brown adipose tissueHigh-fat diet-fed C57BL6J mice
Cinnamomum cassia Presl [89]Increases ATP levels by increasing the mRNA expression of mitochondrial biogenesis-related factors, such as PGC-1α, Nrf1, and T-famHigh-fat diet-induced obese mouse and mouse C2C12 myoblasts
Guarana (Paullinia cupana Kunth) [90]Increases the expression of PGC-1α, CREB1, AMPKA1, Nrf1, Nrf2, and Sirt1 in the muscle and brown adipose tissue and increases mtDNA (mitochondrial DNA) content in the muscleHigh-fat diet-fed C57BL6J mice

MonomerIsorhamnetin [91]Regulates mitochondrial biosynthetic mRNA levels of PGC-1α, Nrf1, and T-fam and increases the mtDNA/nuclear DNA ratio3T3-L1cells
Zeaxanthin [92]Increases mitochondrial DNA content and mRNA levels of genes related to mitochondrial biogenesis, reduces mitochondrial oxidative damage, improves ΔΨm, and eliminates intracellular ROS and mitochondrial superoxide3T3-L1 preadipocytes
Berberine [93]In a mouse model, protects mitochondrial structure and function by reducing ATP abundance and activity of complex I and enhances the activity of complexes II and IV. In a cellular model, decreases ATP abundance, increases ΔΨm and inhibits apoptosisHigh-fat diet-induced obese model in C57BL/6 mice with GLP-1 reduction
Purpurin [94]Regulates ROS and reduces ΔΨm and ATP production3T3-L1 murine preadipocytes and high-fat diet-fed C57BL/6 mice
Epigallocatechin-3-gallate [95]Increases the mtDNA content and the mRNA levels of PGC-1α, Nrf1, and T-fam in brown adipose tissueHigh-fat diet-induced obesity in C57BL/6J mice

2.6. Regulating the Mitochondria to against Myocardial Injury

Myocardial injury can be caused by myocardial infarction, ischemia, inflammatory cell infiltration, poisoning, and so on [33]. The essence of myocardial injury refers to the edema, degeneration, and necrosis of myocardial cells; the breakdown and lysis of myofibrils; and cellular structures, such as mitochondria in severe lesions. Severe myocardial injury can lead to myocarditis and heart failure [34]. Myocardium is the most energy consuming tissue in the human body [35]. Mitochondrial abnormalities play a central role in the pathogenesis and development of various heart diseases, including acute myocardial infarction and cardiomyopathy [36].

In previous studies, it was shown that natural products can protect the heart by regulating the mitochondrial function (Table 7): (1) stabilize ΔΨm and membrane fluidity; (2) protect mitochondrial structure and morphology; (3) adjust mitochondrial apoptotic pathways, reduce the release of proapoptotic factors, and inhibit myocardial cell apoptosis; (4) improve mitochondrial energy metabolism; and (5) enhance SOD and GSH activity, inhibit oxidative stress, and reduce ROS damage.


Types of natural productsNatural productsMitochondrial regulationTypes of diseasesExperimental models

MixturePropolis [96]Reduces the rate of H2O2 produced by mitochondrial respirationMyocardial ischemiaHypothermia-induced ischemia model in C57BL6J mice

MonomerCapsaicin [97]Inhibits the production of ROS, inhibits opening of the mPTP and activation of caspase-3, downregulates Bax, and upregulates Bcl-2I/R injuryAcute myocardial hypoxia/reoxygenation (H/R) injury model in H9C2 cells
Quercetin [98]Increases cell viability, SOD, catalase, and GPx activity, GSH levels, ΔΨm, and GSH/GSSG ratios and reduces LDH and caspase-3 activity, MDA and ROS levels, mPTP openness and the percentage of apoptotic cellsDoxorubicin-caused cardiotoxicityDoxorubicin-treated cardiomyocytes
Luteoloside [99]Decreases levels of lactate dehydrogenase, ROS species, mPTP openness, caspase-3 activity, and apoptotic rateI/R injuryH/R-induced I/R model in H9C2 cardiomyocytes
Astragaloside IV [100]Upregulates mitochondrial Bcl-2 expression, enhances antioxidant capacity, inhibits ROS, increases oxygen consumption, maintains ΔΨm, and inhibits mPTP opening and apoptosisI/R injuryH/R-treated H9C2 cells and anoxia/reoxygenation model in isolated rat heart
Eriodictyol [101]Suppresses the overload of intracellular Ca2+, prevents the overproduction of ROS, blocks mPTP opening, increases the ΔΨm level, and decreases ATP depletion and upregulates Bcl-2 expression and downregulates Bax and caspase-3 expressionMyocardial infarctionH/R-induced I/R model in H9C2 cardiomyocytes
Dihydromyricetin [102]Increases ATP content, mitochondrial DNA content, and citrate synthase activity and decreases ROS level, mitochondrial MnSOD activity, and caspase-3 activityI/R injuryI/R model in mice and H/R-treated cardiomyocytes from mice
Vitexin [103]Reduces ROS levels; improves mitochondrial activity, ΔΨm, and ATP content; increases mfn2 expression, and reduces the recruitment of Drp1 in the mitochondriaI/R injuryI/R model in isolated rat heart and H/R-induced I/R model in H9C2
Honokiol [104]Inhibits ROS production and regulates ΔΨm.I/R injuryI/R model in C57BL/6 mice and H/R-treated cardiomyocytes from neonatal rats
Apigenin [105]Reduces the activity of lactate dehydrogenase and intracellular ROS, alleviates the loss of ΔΨm, prevents mPTP opening, and decreases caspase-3 activity, cytochrome c release, and apoptosisI/R injuryI/R model in isolated rat heart and ischemic/reperfusion medium-induced injury model in cardiomyocytes

3. Similarities and Differences between the Mitochondrial Mechanisms for Natural Products Regulating Different Diseases

As shown in Table 8, there are some common mechanisms in mitochondrial dysfunction among different diseases, and the similarities and differences existed between the mitochondrial mechanisms for natural products regulating different diseases. For instance, almost all the mitochondria-involved diseases, including neurodegenerative disorders, cancer, liver diseases, myocardial injury, diabetes, and obesity, are related with mitochondrial energy metabolism, which can be remedied by natural products. However, fatty acid oxidation is specifically involved with obesity and fatty liver disease, which can also be regulated by natural products. Furthermore, a variety of natural products can remedy the mitochondria through multiple mechanisms to cure various diseases.


DiseasesMajor mechanismsNatural products

CancerEnergy metabolism obstructionRhein [39]
Gracillin [44]
Oxidative stressBulbine frutescens [37]
Bullfrog oil [38]
Orientin [40]
Asparanin A [42]
Gracillin [44]
ApoptosisBulbine frutescens [37]
Orientin [40]
Licochalcone A [41]
Asparanin A [42]
Parameritannin A-2 [43]
Cernumidine [45]
Mitochondrial membrane potential imbalanceBullfrog oil [38]
Rhein [39]
Asparanin A [42]
Cernumidine [45]

Neurodegenerative diseasesEnergy metabolism obstructionSolanum melongena extract [46]
Ganoderma lucidum [47]
α-Arbutin [51]
Auraptene [54]
Oxidative stressSolanum melongena extract [46]
Linalool [48]
α-Arbutin [51]
Naringenin [52]
Apigenin [53]
Auraptene [54]
ApoptosisGanoderma lucidum [47]
Cinnamic acid derivatives [49]
Proanthocyanidins [50]
Naringenin [52]
Apigenin [53]
Naringenin [55]
Ulmoside A [56]
Mitochondrial membrane potential imbalanceGanoderma lucidum [47]
Linalool [48]
α-Arbutin [51]
Mitochondrial fusion, division, and autophagyCelastrol [57]

Liver diseasesEnergy metabolism obstructionRooibos tea [58]
Cimicifuga racemosa extract [59]
Polygonatum kingianum [61]
Betaine [63]
Nicotinamide riboside [64]
Puerarin [65]
Punica granatum L. [62]
Silybin [67]
Salvianolic acid B [68]
Oxidative stressCimicifuga racemosa extract [59]
Sipjeondaebo-tang [60]
Polygonatum kingianum [61]
Nicotinamide riboside [64]
Diosgenin [66]
Silybin [67]
NecroX-7 [69]
ApoptosisCimicifuga racemosa extract [59]
Polygonatum kingianum [61]
Betaine [63]
Silybin [67]
Salvianolic acid B [68]
Mitochondrial membrane potential imbalanceCimicifuga racemosa extract [59]
Sipjeondaebo-tang [60]
Diosgenin [66]
Salvianolic acid B [68]
NecroX-7 [69]
Fatty acid oxidationSilybin [67]
NecroX-7 [69]

T2DMEnergy metabolism obstructionPolysaccharides from Portulaca oleracea L. [70]
Korean red ginseng [71]
Berberine [72]
Quercetin [73]
Theaflavins [74]
Puerarin [76]
Mitochondrial membrane potential imbalancePolysaccharides from Portulaca oleracea L. [70]
Silibinin [75]
ApoptosisSilibinin [75]
Mitochondrial fusion, division, and autophagyKorean red ginseng [71]
Quercetin [73]
Theaflavins [74]
Silibinin [75]
Puerarin [76]

Diabetes complicationsEnergy metabolism obstructionQiDiTangShen granules [77]
Shengmai San [78]
Water extracts of Liuwei Dihuang [79]
Salidroside [82]
Hydroxytyrosol [85]
Oxidative stressWater extracts of Liuwei Dihuang [79]
Anthocyanins [80]
Ginsenoside Rb1 [84]
Hydroxytyrosol [85]
ApoptosisAnthocyanins [80]
Orientin [81]
Astragalus polysaccharides [83]
Ginsenoside Rb1 [84]
Mitochondrial membrane potential imbalanceOrientin [81]
Water extracts of Liuwei Dihuang [79]
Mitochondrial fusion, division, and autophagyOrientin [81]
QiDiTangShen granules [77]
Salidroside [82]

ObesityEnergy metabolism obstructionMelinjo (Gnetum gnemon L.) seed extract [88]
Cinnamomum cassia Presl [89]
Isorhamnetin [91]
Zeaxanthin [92]
Berberine [93]
Purpurin [94]
Epigallocatechin-3-gallate [95]
Guarana (Paullinia cupana Kunth) [90]
Mitochondrial membrane potential imbalanceZeaxanthin [92]
Berberine [93]
Purpurin [94]
Mitochondrial fusion, division, and autophagyCinnamomum cassia Presl [89]
Isorhamnetin [91]
Zeaxanthin [92]
Epigallocatechin-3-gallate [95]
Guarana (Paullinia cupana Kunth) [90]
Fatty acid metabolismGreen tea [86]

Myocardial injuryEnergy metabolism obstructionPropolis [96]
Luteoloside [99]
Eriodictyol [101]
Dihydromyricetin [102]
Vitexin [103]
Apigenin [105]
Oxidative stressCapsaicin [97]
Quercetin [98]
Luteoloside [99]
Astragaloside IV [100]
Eriodictyol [101]
Dihydromyricetin [102]
Vitexin [103]
Honokiol [104]
Apigenin [105]
ApoptosisCapsaicin [97]
Quercetin [98]
Luteoloside [99]
Astragaloside IV [100]
Eriodictyol [101]
Dihydromyricetin [102]
Apigenin [105]
Mitochondrial membrane potential imbalanceCapsaicin [97]
Quercetin [98]
Luteoloside [99]
Astragaloside IV [100]
Eriodictyol [101]
Vitexin [103]
Honokiol [104]
Apigenin [105]

4. Conclusion

Mitochondria are cytoplasmic organelles responsible for cell survival and cell death. Mitochondrial dysfunction has been reported to be involved in many diseases. Many natural products can regulate the mitochondria in various ways to alleviate related diseases (Figure 1). However, only a few have become clinical drugs for treating patients, and many compounds have not been used in clinical practice. Additional studies (such as pharmacodynamics, toxicology, and structure-activity relationship) of these compounds should be performed, which will promote that more natural products will be available for clinical usage. In addition, the monomers that can regulate the mitochondria in many natural extracts remain unclear, and further studies are warranted to identify natural monomers that can regulate the mitochondria. With the deepening of research, it is believed that more natural products that can regulate the mitochondria have the potential to be used in treating diseases, which is of utmost importance.

Abbreviations

AFLD:Alcoholic fatty liver disease
ASH:Alcoholic steatohepatitis
DM:Diabetes mellitus
H/R:Hypoxia/reoxygenation
I/R:Ischemia/reperfusion
IR:Insulin resistance
LPS:Lipopolysaccharides
ΔΨm:Mitochondrial membrane potential
MPTP:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
NAFLD:Nonalcoholic fatty liver disease
NASH:Nonalcoholic steatohepatitis
T1DM:Type 1 diabetes mellitus
T2DM:Type 2 diabetes mellitus.

Data Availability

My article is a summary, so there is no data to provide.

Publication of this manuscript has been approved by all co-authors.

Conflicts of Interest

The authors declare that there is no duality of interest associated with this manuscript.

Authors’ Contributions

Jian-Kang Mu and Yan-Qin Li have contributed equally to this work.

Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (Grants 81660596, 81460623, and 81760733) and the Application and Basis Research Project of Yunnan China (Grants 2019FF002-061 and 2017FF117-013).

References

  1. F. Wang, M.-A. Ogasawara, and P. Huang, “Small mitochondria-targeting molecules as anti-cancer agents,” Molecular Aspects of Medicine, vol. 31, no. 1, pp. 75–92, 2010. View at: Publisher Site | Google Scholar
  2. J. R. Friedman and J. Nunnari, “Mitochondrial form and function,” Nature, vol. 505, no. 7483, pp. 335–343, 2014. View at: Publisher Site | Google Scholar
  3. V. Eisner, M. Picard, and G. Hajnóczky, “Mitochondrial dynamics in adaptive and maladaptive cellular stress responses,” Nature Cell Biology, vol. 20, no. 7, pp. 755–765, 2018. View at: Publisher Site | Google Scholar
  4. J. B. Spinelli and M. C. Haigis, “The multifaceted contributions of mitochondria to cellular metabolism,” Nature Cell Biology, vol. 20, no. 7, pp. 745–754, 2018. View at: Publisher Site | Google Scholar
  5. Y. Wang, X. Fan, H. Qu, X. Gao, and Y. Cheng, “Strategies and techniques for multi-component drug design from medicinal herbs and traditional chinese medicine,” Current Topics in Medicinal Chemistry, vol. 12, no. 12, pp. 1356–1362, 2012. View at: Publisher Site | Google Scholar
  6. B. Wang, J. Deng, Y. Gao, L. Zhu, R. He, and Y. Xu, “The screening toolbox of bioactive substances from natural products: A review,” Fitoterapia, vol. 82, no. 8, pp. 1141–1151, 2011. View at: Publisher Site | Google Scholar
  7. S. Fulda, “Tumor resistance to apoptosis,” International Journal of Cancer, vol. 124, no. 3, pp. 511–515, 2009. View at: Publisher Site | Google Scholar
  8. P. Golstein and G. Kroemer, “Cell death by necrosis: towards a molecular definition,” Trends in Biochemical Sciences, vol. 32, no. 1, pp. 37–43, 2007. View at: Publisher Site | Google Scholar
  9. A.-V. Kudryavtseva, G.-S. Krasnov, A.-A. Dmitriev et al., “Mitochondrial dysfunction and oxidative stress in aging and cancer,” Oncotarget, vol. 7, no. 29, pp. 44879–44905, 2016. View at: Publisher Site | Google Scholar
  10. J.-A. Petros, A.-K. Baumann, E. Ruiz-Pesini et al., “mtDNA mutations increase tumorigenicity in prostate cancer,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 3, pp. 719–724, 2005. View at: Publisher Site | Google Scholar
  11. G. Lou, K. Palikaras, S. Lautrup, M. Scheibye-Knudsen, N. Tavernarakis, and E. F. Fang, “Mitophagy and neuroprotection,” Trends in Molecular Medicine, vol. 26, no. 1, pp. 8–20, 2020. View at: Publisher Site | Google Scholar
  12. K. Panchal and A.-K. Tiwari, “Mitochondrial dynamics, a key executioner in neurodegenerative diseases,” Mitochondrion, vol. 47, pp. 151–173, 2019. View at: Publisher Site | Google Scholar
  13. Y. Luo, A. Hoffer, B. Hoffer, and X. Qi, “Mitochondria: a therapeutic target for Parkinson’s disease?” International Journal of Molecular Sciences, vol. 16, no. 9, pp. 20704–20730, 2015. View at: Publisher Site | Google Scholar
  14. X. Zhang, X. Wu, Q. Hu et al., “Mitochondrial DNA in liver inflammation and oxidative stress,” Life Sciences, vol. 236, article 116464, 2019. View at: Publisher Site | Google Scholar
  15. E. Crosas-Molist and I. Fabregat, “Role of NADPH oxidases in the redox biology of liver fibrosis,” Redox Biology, vol. 6, pp. 106–111, 2015. View at: Publisher Site | Google Scholar
  16. T.-A. Ajith, “Role of mitochondria and mitochondria-targeted agents in non-alcoholic fatty liver disease,” Clinical and Experimental Pharmacology and Physiology, vol. 45, no. 5, pp. 413–421, 2018. View at: Publisher Site | Google Scholar
  17. A.-M. Schmidt, “Diabetes mellitus and cardiovascular disease,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 39, no. 4, pp. 558–568, 2019. View at: Publisher Site | Google Scholar
  18. S. Fujimaki and T. Kuwabara, “Diabetes-induced dysfunction of mitochondria and stem cells in skeletal muscle and the nervous system,” International Journal of Molecular Sciences, vol. 18, no. 10, p. 2147, 2017. View at: Publisher Site | Google Scholar
  19. D. M. D'Souza, D. Al-Sajee, and T. J. Hawke, “Diabetic myopathy: impact of diabetes mellitus on skeletal muscle progenitor cells,” Frontiers in Physiology, vol. 4, p. 379, 2013. View at: Publisher Site | Google Scholar
  20. F. Zatterale, M. Longo, J. Naderi et al., “Chronic adipose tissue inflammation linking obesity to insulin resistance and type 2 diabetes,” Frontiers in Physiology, vol. 10, p. 1607, 2020. View at: Publisher Site | Google Scholar
  21. Y. Lin and Z. Sun, “Current views on type 2 diabetes,” The Journal of Endocrinology, vol. 204, no. 1, pp. 1–11, 2010. View at: Publisher Site | Google Scholar
  22. L. Vilarinho, F.-M. Santorelli, I. Coelho et al., “The mitochondrial DNA A3243G mutation in Portugal: clinical and molecular studies in 5 families,” Journal of the Neurological Sciences, vol. 163, no. 2, pp. 168–174, 1999. View at: Publisher Site | Google Scholar
  23. E. Heyman, F. Daussin, V. Wieczorek et al., “Muscle oxygen supply and use in type 1 diabetes, from ambient air to the mitochondrial respiratory chain: is there a limiting step?” Diabetes Care, vol. 43, no. 1, pp. 209–218, 2020. View at: Publisher Site | Google Scholar
  24. T. Jelenik, U. Flögel, E. Álvarez-Hernández et al., “Insulin resistance and vulnerability to cardiac ischemia,” Diabetes, vol. 67, no. 12, pp. 2695–2702, 2018. View at: Publisher Site | Google Scholar
  25. N.-B. Flemming, L.-A. Gallo, M.-S. Ward, and J.-M. Forbes, “Tapping into mitochondria to find novel targets for diabetes complications,” Current Drug Targets, vol. 17, no. 12, pp. 1341–1349, 2016. View at: Publisher Site | Google Scholar
  26. R.-A. Kowluru, “Mitochondrial stability in diabetic retinopathy: lessons learned from epigenetics,” Diabetes, vol. 68, no. 2, pp. 241–247, 2019. View at: Publisher Site | Google Scholar
  27. R. Blake and I.-A. Trounce, “Mitochondrial dysfunction and complications associated with diabetes,” Biochimica et Biophysica Acta (BBA) - General Subjects, vol. 1840, no. 4, pp. 1404–1412, 2014. View at: Publisher Site | Google Scholar
  28. P.-Z. Wei and C.-C. Szeto, “Mitochondrial dysfunction in diabetic kidney disease,” Clinica Chimica Acta, vol. 496, pp. 108–116, 2019. View at: Publisher Site | Google Scholar
  29. E. Björnson, M. Adiels, M.-R. Taskinen, and J. Borén, “Kinetics of plasma triglycerides in abdominal obesity,” Current Opinion in Lipidology, vol. 28, no. 1, pp. 1–18, 2016. View at: Publisher Site | Google Scholar
  30. M. Blüher, “Adipose tissue dysfunction contributes to obesity related metabolic diseases,” Best Practice & Research. Clinical Endocrinology & Metabolism, vol. 27, no. 2, pp. 163–177, 2013. View at: Publisher Site | Google Scholar
  31. A.-H. de Mello, A.-B. Costa, J.-D.-G. Engel, and G.-T. Rezin, “Mitochondrial dysfunction in obesity,” Life Sciences, vol. 192, pp. 26–32, 2018. View at: Publisher Site | Google Scholar
  32. C.-S. Lai, J.-C. Wu, C.-T. Ho, and M.-H. Pan, “Chemoprevention of obesity by dietary natural compounds targeting mitochondrial regulation,” Molecular Nutrition & Food Research, vol. 61, no. 6, 2017. View at: Publisher Site | Google Scholar
  33. S. Hernandez-Resendiz, K. Chinda, S.-B. Ong, H. Cabrera-Fuentes, C. Zazueta, and D. J. Hausenloy, “The role of redox dysregulation in the inflammatory response to acute myocardial ischaemia-reperfusion injury - adding fuel to the fire,” Current Medicinal Chemistry, vol. 25, no. 11, pp. 1275–1293, 2018. View at: Publisher Site | Google Scholar
  34. M. Neri, I. Riezzo, N. Pascale, C. Pomara, and E. Turillazzi, “Ischemia/reperfusion injury following acute myocardial infarction: a critical issue for clinicians and forensic pathologists,” Mediators of Inflammation, vol. 2017, Article ID 7018393, 14 pages, 2017. View at: Publisher Site | Google Scholar
  35. J.-L. Pohjoismäki and S. Goffart, “The role of mitochondria in cardiac development and protection,” Free Radical Biology & Medicine, vol. 106, pp. 345–354, 2017. View at: Publisher Site | Google Scholar
  36. M. Jašová, I. Kancirová, I. Waczulíková, and M. Ferko, “Mitochondria as a target of cardioprotection in models of preconditioning,” Journal of Bioenergetics and Biomembranes, vol. 49, no. 5, pp. 357–368, 2017. View at: Publisher Site | Google Scholar
  37. P. P. Kushwaha, P. S. Vardhan, P. Kapewangolo et al., “Bulbine frutescens phytochemical inhibits notch signaling pathway and induces apoptosis in triple negative and luminal breast cancer cells,” Life Sciences, vol. 234, article 116783, 2019. View at: Publisher Site | Google Scholar
  38. L. Amaral-Machado, W. N. Oliveira, É. N. Alencar et al., “Bullfrog oil (Rana catesbeiana Shaw) induces apoptosis, in A2058 human melanoma cells by mitochondrial dysfunction triggered by oxidative stress,” Biomedicine & Pharmacotherapy, vol. 117, article 109103, 2019. View at: Publisher Site | Google Scholar
  39. L. Wu, K. Cao, Z. Ni et al., “Rhein reverses doxorubicin resistance in SMMC-7721 liver cancer cells by inhibiting energy metabolism and inducing mitochondrial permeability transition pore opening,” BioFactors, vol. 45, no. 1, pp. 85–96, 2019. View at: Publisher Site | Google Scholar
  40. K. Thangaraj, B. Balasubramanian, S. Park, K. Natesan, W. Liu, and V. Manju, “Orientin induces G0/G1 cell cycle arrest and mitochondria mediated intrinsic apoptosis in human colorectal carcinoma HT29 cells,” Biomolecules, vol. 9, no. 9, p. 418, 2019. View at: Publisher Site | Google Scholar
  41. S. H. Hong, H.-J. Cha, H. Hwang-Bo et al., “Anti-proliferative and pro-apoptotic effects of licochalcone a through ROS-mediated cell cycle arrest and apoptosis in human bladder cancer cells,” International Journal of Molecular Sciences, vol. 20, no. 15, p. 3820, 2019. View at: Publisher Site | Google Scholar
  42. F. Zhang, Y.-Y. Zhang, Y.-S. Sun et al., “Asparanin a from asparagus officinalis L. induces G0/G1 cell cycle arrest and apoptosis in human endometrial carcinoma ishikawa cells via mitochondrial and PI3K/AKT signaling pathways,” Journal of Agricultural and Food Chemistry, vol. 68, no. 1, pp. 213–224, 2019. View at: Publisher Site | Google Scholar
  43. L. Liang, A. Amin, W.-Y. Cheung et al., “Parameritannin A-2 from Urceola huaitingii enhances doxorubicin-induced mitochondria-dependent apoptosis by inhibiting the PI3K/Akt, ERK1/2 and p38 pathways in gastric cancer cells,” Chemico-Biological Interactions, vol. 316, article 108924, 2020. View at: Publisher Site | Google Scholar
  44. H.-Y. Min, H.-J. Jang, K. H. Park et al., “The natural compound gracillin exerts potent antitumor activity by targeting mitochondrial complex II,” Cell Death & Disease, vol. 10, no. 11, p. 810, 2019. View at: Publisher Site | Google Scholar
  45. M. A. Miranda, A. Mondal, M. Sachdeva et al., “Chemosensitizing effect of cernumidine extracted from solanum cernuum on bladder cancer cells in vitro,” Chemistry & Biodiversity, vol. 16, no. 10, article e1900334, 2019. View at: Publisher Site | Google Scholar
  46. Y. Youn, S.‐. H. Jeon, H.‐. Y. Jin, D. N. Che, S.‐. I. Jang, and Y.‐. S. Kim, “Chlorogenic acid-rich Solanum melongena extract has protective potential against rotenone-induced neurotoxicity in PC-12 cells,” Journal of Food Biochemistry, vol. 43, no. 11, article e12999, 2019. View at: Publisher Site | Google Scholar
  47. Z.-l. Ren, C.-d. Wang, T. Wang et al., “Ganoderma lucidum extract ameliorates MPTP-induced parkinsonism and protects dopaminergic neurons from oxidative stress via regulating mitochondrial function, autophagy, and apoptosis,” Acta Pharmacologica Sinica, vol. 40, no. 4, pp. 441–450, 2019. View at: Publisher Site | Google Scholar
  48. A. M. Sabogal-Guáqueta, F. Hobbie, A. Keerthi et al., “Linalool attenuates oxidative stress and mitochondrial dysfunction mediated by glutamate and NMDA toxicity,” Biomedicine & Pharmacotherapy, vol. 118, article 109295, 2019. View at: Publisher Site | Google Scholar
  49. W.-X. Zhang, H. Wang, H.-R. Cui et al., “Design, synthesis and biological evaluation of cinnamic acid derivatives with synergetic neuroprotection and angiogenesis effect,” European Journal of Medicinal Chemistry, vol. 183, article 111695, 2019. View at: Publisher Site | Google Scholar
  50. J. Zhang, X. Zhang, C. Wen, Y. Duan, and H. Zhang, “Lotus seedpod proanthocyanidins protect against neurotoxicity after methyl- mercuric chloride injury,” Ecotoxicology and Environmental Safety, vol. 183, article 109560, 2019. View at: Publisher Site | Google Scholar
  51. Y. Ding, D. Kong, T. Zhou et al., “α-Arbutin protects against Parkinson's disease-associated mitochondrial dysfunction in vitro and in vivo,” Neuromolecular Medicine, vol. 22, no. 1, pp. 56–67, 2020. View at: Publisher Site | Google Scholar
  52. A.-M. Krishna Chandran, H. Christina, S. Das, K.-D. Mumbrekar, and B.-S. Satish Rao, “Neuroprotective role of naringenin against methylmercury induced cognitive impairment and mitochondrial damage in a mouse model,” Environmental Toxicology and Pharmacology, vol. 71, article 103224, 2019. View at: Publisher Site | Google Scholar
  53. F. Zhao, Y. Dang, R. Zhang et al., “Apigenin attenuates acrylonitrile-induced neuro-inflammation in rats: involved of inactivation of the TLR4/NF-κB signaling pathway,” International Immunopharmacology, vol. 75, article 105697, 2019. View at: Publisher Site | Google Scholar
  54. Y. Jang, H. Choo, M. J. Lee et al., “Auraptene mitigates Parkinson's disease-like behavior by protecting inhibition of mitochondrial respiration and scavenging reactive oxygen species,” International Journal of Molecular Sciences, vol. 20, no. 14, p. 3409, 2019. View at: Publisher Site | Google Scholar
  55. Y. Jin and H. Wang, “Naringenin inhibit the hydrogen peroxide-induced SH-SY5Y cells injury through Nrf 2/HO-1 pathway,” Neurotoxicity Research, vol. 36, no. 4, pp. 796–805, 2019. View at: Publisher Site | Google Scholar
  56. P. Gupta, A. Singh, S. Tiwari, A. Mishra, R. Maurya, and S. Singh, “Ulmosides A: flavonoid 6-C-glycosides from ulmus wallichiana attenuates lipopolysacchride induced oxidative stress, apoptosis and neuronal death,” NeuroToxicology, vol. 73, pp. 100–111, 2019. View at: Publisher Site | Google Scholar
  57. M.-W. Lin, C. C. Lin, Y.-H. Chen, H.-B. Yang, and S.-Y. Hung, “Celastrol inhibits dopaminergic neuronal death of Parkinson's disease through activating mitophagy,” Antioxidants, vol. 9, no. 1, p. 37, 2020. View at: Publisher Site | Google Scholar
  58. O. Uličná, O. Vančová, J. Kucharská, P. Janega, and I. Waczulíková, “Rooibos tea (Aspalathus linearis) ameliorates the CCl4-induced injury to mitochondrial respiratory function and energy production in rat liver,” General Physiology and Biophysics, vol. 38, no. 1, pp. 15–25, 2019. View at: Publisher Site | Google Scholar
  59. M. Rabenau, M. Unger, J. Drewe, and C. Culmsee, “Metabolic switch induced by Cimicifuga racemosa extract prevents mitochondrial damage and oxidative cell death,” Phytomedicine, vol. 52, pp. 107–116, 2019. View at: Publisher Site | Google Scholar
  60. S. M. Park, S. W. Kim, E. H. Jung et al., “Sipjeondaebo-tang qlleviates oxidative stress-mediated liver injury through activation of the CaMKK2-AMPK signaling pathway,” Evidence-Based Complementary and Alternative Medicine, vol. 2018, Article ID 8609285, 13 pages, 2018. View at: Publisher Site | Google Scholar
  61. X.-X. Yang, X. Wang, T.-T. Shi et al., “Mitochondrial dysfunction in high-fat diet-induced nonalcoholic fatty liver disease: The alleviating effect and its mechanism of Polygonatum kingianum,” Biomedicine & Pharmacotherapy, vol. 117, article 109083, 2019. View at: Publisher Site | Google Scholar
  62. X. Zou, C. Yan, Y. Shi et al., “Mitochondrial dysfunction in obesity-associated nonalcoholic fatty liver disease: the protective effects of pomegranate with its active component punicalagin,” Antioxidants & Redox Signaling, vol. 21, no. 11, pp. 1557–1570, 2014. View at: Publisher Site | Google Scholar
  63. M. Jung Kim, “Betaine enhances the cellular survival via mitochondrial fusion and fission factors, MFN2 and DRP1,” Animal Cells and Systems, vol. 22, no. 5, pp. 289–298, 2018. View at: Publisher Site | Google Scholar
  64. S. Wang, T. Wan, M. Ye et al., “Nicotinamide riboside attenuates alcohol induced liver injuries via activation of SirT1/PGC-1α/mitochondrial biosynthesis pathway,” Redox Biology, vol. 17, pp. 89–98, 2018. View at: Publisher Site | Google Scholar
  65. S. Wang, F.-J. Yang, L.-C. Shang, Y. H. Zhang, Y. Zhou, and X. L. Shi, “Puerarin protects against high-fat high-sucrose diet-induced non-alcoholic fatty liver disease by modulating PARP-1/PI3K/AKT signaling pathway and facilitating mitochondrial homeostasis,” Phytotherapy Research, vol. 33, no. 9, pp. 2347–2359, 2019. View at: Publisher Site | Google Scholar
  66. K. Fang, F. Wu, G. Chen et al., “Diosgenin ameliorates palmitic acid-induced lipid accumulation via AMPK/ACC/CPT-1A and SREBP-1c/FAS signaling pathways in LO2 cells,” BMC Complementary and Alternative Medicine, vol. 19, no. 1, p. 255, 2019. View at: Publisher Site | Google Scholar
  67. G. Vecchione, E. Grasselli, F. Cioffi et al., “The nutraceutic silybin counteracts excess lipid accumulation and ongoing oxidative stress in an in vitro model of non-alcoholic fatty liver disease progression,” Frontiers in Nutrition, vol. 4, p. 42, 2017. View at: Publisher Site | Google Scholar
  68. Y.-C. Wang, W.-Z. Kong, Q.-M. Jin, J. Chen, and L. Dong, “Effects of salvianolic acid B on liver mitochondria of rats with nonalcoholic steatohepatitis,” World Journal of Gastroenterology, vol. 21, no. 35, pp. s10104–s10112, 2015. View at: Publisher Site | Google Scholar
  69. H.-K. Chung, Y.-K. Kim, J.-H. Park et al., “The indole derivative necrox-7 improves nonalcoholic steatohepatitis in ob/ob mice through suppression of mitochondrial ROS/RNS and inflammation,” Liver International, vol. 35, no. 4, pp. 1341–1353, 2015. View at: Publisher Site | Google Scholar
  70. Q. Hu, Q. Niu, H. Song et al., “Polysaccharides from Portulaca oleracea L. regulated insulin secretion in INS-1 cells through voltage-gated Na + channel,” Biomedicine & Pharmacotherapy, vol. 109, pp. 876–885, 2019. View at: Publisher Site | Google Scholar
  71. J.-K. Park, J.-Y. Shim, A.-R. Cho, M.-R. Cho, and Y.-J. Lee, “Korean red ginseng protects against mitochondrial damage and intracellular inflammation in an animal model of type 2 diabetes mellitus,” Journal of Medicinal Food, vol. 21, no. 6, pp. 544–550, 2018. View at: Publisher Site | Google Scholar
  72. M. Javadipour, M. Rezaei, E. Keshtzar, and M.-J. Khodayar, “Metformin in contrast to berberine reversed arsenic-induced oxidative stress in mitochondria from rat pancreas probably via Sirt3‐dependent pathway,” Journal of Biochemical and Molecular Toxicology, vol. 33, no. 9, 2019. View at: Publisher Site | Google Scholar
  73. M.-J. Houghton, A. Kerimi, S. Tumova, J.-P. Boyle, and G. Williamson, “Quercetin preserves redox status and stimulates mitochondrial function in metabolically-stressed HepG2 cells,” Free Radical Biology & Medicine, vol. 129, pp. 296–309, 2018. View at: Publisher Site | Google Scholar
  74. T. Tong, N. Ren, P. Soomi et al., “Theaflavins improve insulin sensitivity through regulating mitochondrial biosynthesis in palmitic acid-induced HepG2 cells,” Molecules, vol. 23, no. 12, p. 3382, 2018. View at: Publisher Site | Google Scholar
  75. Y. Sun, J. Yang, W. Liu et al., “Attenuating effect of silibinin on palmitic acid-induced apoptosis and mitochondrial dysfunction in pancreatic β-cells is mediated by estrogen receptor alpha,” Molecular and Cellular Biochemistry, vol. 460, no. 1-2, pp. 81–92, 2019. View at: Publisher Site | Google Scholar
  76. X.-F. Chen, L. Wang, Y.-Z. Wu et al., “Effect of puerarin in promoting fatty acid oxidation by increasing mitochondrial oxidative capacity and biogenesis in skeletal muscle in diabetic rats,” Nutrition & Diabetes, vol. 8, no. 1, 2018. View at: Publisher Site | Google Scholar
  77. X. Wang, L. Zhao, A.-K. Ajay et al., “QiDiTangShen granules activate renal nutrient-sensing associated autophagy in db/db mice,” Frontiers in Physiology, vol. 10, p. 1224, 2019. View at: Publisher Site | Google Scholar
  78. J. Tian, W. Tang, M. Xu et al., “Shengmai san alleviates diabetic cardiomyopathy through improvement of mitochondrial lipid metabolic disorder,” Cellular Physiology and Biochemistry, vol. 50, no. 5, pp. 1726–1739, 2018. View at: Publisher Site | Google Scholar
  79. Y.-T. Tseng, W.-H. Chang, C.-C. Lin, F. R. Chang, P. C. Wu, and Y. C. Lo, “Protective effects of Liuwei Dihuang water extracts on diabetic muscle atrophy,” Phytomedicine, vol. 53, pp. 96–106, 2019. View at: Publisher Site | Google Scholar
  80. J. Wei, H. Wu, H. Zhang et al., “Anthocyanins inhibit high glucose-induced renal tubular cell apoptosis caused by oxidative stress in db/db mice,” International Journal of Molecular Medicine, vol. 41, no. 3, pp. 1608–1618, 2018. View at: Publisher Site | Google Scholar
  81. Z.-L. Kong, K. Che, J.-X. Hu et al., “Orientin protects podocytes from high glucose induced apoptosis through mitophagy,” Chemistry & Biodiversity, vol. 17, no. 3, article e1900647, 2020. View at: Publisher Site | Google Scholar
  82. H. Xue, P. Li, Y. Luo et al., “Salidroside stimulates the Sirt1/PGC-1α axis and ameliorates diabetic nephropathy in mice,” Phytomedicine, vol. 54, pp. 240–247, 2019. View at: Publisher Site | Google Scholar
  83. S. Sun, S. Yang, M. Dai et al., “The effect of Astragalus polysaccharides on attenuation of diabetic cardiomyopathy through inhibiting the extrinsic and intrinsic apoptotic pathways in high glucose -stimulated H9C2 cells,” BMC Complementary and Alternative Medicine, vol. 17, no. 1, p. 310, 2017. View at: Publisher Site | Google Scholar
  84. F. Nan, G. Sun, W. Xie et al., “Ginsenoside Rb1 mitigates oxidative stress and apoptosis induced by methylglyoxal in SH-SY5Y cells via the PI3K/Akt pathway,” Molecular and Cellular Probes, vol. 48, article 101469, 2019. View at: Publisher Site | Google Scholar
  85. A. Zheng, H. Li, J. Xu et al., “Hydroxytyrosol improves mitochondrial function and reduces oxidative stress in the brain of db/db mice: role of AMP-activated protein kinase activation,” The British Journal of Nutrition, vol. 113, no. 11, pp. 1667–1676, 2015. View at: Publisher Site | Google Scholar
  86. L.-S. Lee, J.-H. Choi, M.-J. Sung et al., “Green tea changes serum and liver metabolomic profiles in mice with high-fat diet-induced obesity,” Molecular Nutrition & Food Research, vol. 59, no. 4, pp. 784–794, 2015. View at: Publisher Site | Google Scholar
  87. S. Seo, S.-M. Jo, J. Kim, M. Lee, Y. Lee, and I. Kang, “Peanut sprout extracts attenuate triglyceride accumulation by promoting mitochondrial fatty acid oxidation in adipocytes,” International Journal of Molecular Sciences, vol. 20, no. 5, p. 1216, 2019. View at: Publisher Site | Google Scholar
  88. T. Yoneshiro, R. Kaede, K. Nagaya et al., “Melinjo (Gnetum gnemon L) seed extract induces uncoupling protein 1 expression in brown fat and protects mice against diet-induced obesity, inflammation, and insulin resistance,” Nutrition Research, vol. 58, pp. 17–25, 2018. View at: Publisher Site | Google Scholar
  89. M.-Y. Song, S.-Y. Kang, A. Kang, J. H. Hwang, Y. K. Park, and H. W. Jung, “Cinnamomum cassia Prevents high-fat diet-induced obesity in mice through the increase of muscle energy,” The American Journal of Chinese Medicine, vol. 45, no. 5, pp. 1017–1031, 2017. View at: Publisher Site | Google Scholar
  90. N.-D.-S. Lima, L. Teixeira, A. Gambero, and M.-L. Ribeiro, “Guarana (Paullinia cupana) stimulates mitochondrial biogenesis in mice fed high-fat diet,” Nutrients, vol. 10, no. 2, 2018. View at: Publisher Site | Google Scholar
  91. M.-S. Lee and Y. Kim, “Effects of isorhamnetin on adipocyte mitochondrial biogenesis and AMPK activation,” Molecules, vol. 23, no. 8, p. 1853, 2018. View at: Publisher Site | Google Scholar
  92. M. Liu, M. Zheng, D. Cai et al., “Zeaxanthin promotes mitochondrial biogenesis and adipocyte browningviaAMPKα1 activation,” Food & Function, vol. 10, no. 4, pp. 2221–2233, 2019. View at: Publisher Site | Google Scholar
  93. Y. Sun, C. Jin, X. Zhang, W. Jia, J. le, and J. Ye, “Restoration of GLP-1 secretion by berberine is associated with protection of colon enterocytes from mitochondrial overheating in diet-induced obese mice,” Nutrition & Diabetes, vol. 8, no. 1, p. 53, 2018. View at: Publisher Site | Google Scholar
  94. W. Nam, S.-H. Nam, S.-P. Kim, C. Levin, and M. Friedman, “Anti-adipogenic and anti-obesity activities of purpurin in 3T3-L1 preadipocyte cells and in mice fed a high-fat diet,” BMC Complementary and Alternative Medicine, vol. 19, no. 1, p. 364, 2019. View at: Publisher Site | Google Scholar
  95. M.-S. Lee, Y. Shin, S. Jung, and Y. Kim, “Effects of epigallocatechin-3-gallate on thermogenesis and mitochondrial biogenesis in brown adipose tissues of diet-induced obese mice,” Food & Nutrition Research, vol. 61, no. 1, article 1325307, 2017. View at: Publisher Site | Google Scholar
  96. A. Braik, M. Lahouel, R. Merabe, M.-R. Djebar, and D. Morin, “Myocardial protection by propolis during prolonged hypothermic preservation,” Cryobiology, vol. 88, pp. 29–37, 2019. View at: Publisher Site | Google Scholar
  97. J. Huang, Z. Liu, P. Xu et al., “Capsaicin prevents mitochondrial damage, protects cardiomyocytes subjected to anoxia/reoxygenation injury mediated by 14-3-3η/Bcl-2,” European Journal of Pharmacology, vol. 819, pp. 43–50, 2018. View at: Publisher Site | Google Scholar
  98. X. Chen, X. Peng, Y. Luo et al., “Quercetin protects cardiomyocytes against doxorubicin-induced toxicity by suppressing oxidative stress and improving mitochondrial function via 14-3-3γ,” Toxicology Mechanisms and Methods, vol. 29, no. 5, pp. 344–354, 2019. View at: Publisher Site | Google Scholar
  99. Z. Liu, L. Yang, J. Huang et al., “Luteoloside attenuates anoxia/reoxygenation-induced cardiomyocytes injury via mitochondrial pathway mediated by 14-3-3η protein,” Phytotherapy Research, vol. 32, no. 6, pp. 1126–1134, 2018. View at: Publisher Site | Google Scholar
  100. Y. Luo, Q. Wan, M. Xu et al., “Nutritional preconditioning induced by astragaloside IV on isolated hearts and cardiomyocytes against myocardial ischemia injury via improving Bcl-2-mediated mitochondrial function,” Chemico-Biological Interactions, vol. 309, article 108723, 2019. View at: Publisher Site | Google Scholar
  101. Y. Xie, R. Ji, and M. Han, “Eriodictyol protects H9c2 cardiomyocytes against the injury induced by hypoxia/reoxygenation by improving the dysfunction of mitochondria,” Experimental and Therapeutic Medicine, vol. 17, no. 1, pp. 551–557, 2019. View at: Publisher Site | Google Scholar
  102. L. Wei, X. Sun, X. Qi, Y. Zhang, Y. Li, and Y. Xu, “Dihydromyricetin ameliorates cardiac ischemia/reperfusion injury through Sirt3 activation,” Bio Med Research International, vol. 2019, article 6803943, pp. 1–9, 2019. View at: Publisher Site | Google Scholar
  103. W. Xue, X. Wang, H. Tang et al., “Vitexin attenuates myocardial ischemia/reperfusion injury in rats by regulating mitochondrial dysfunction induced by mitochondrial dynamics imbalance,” Biomedicine & Pharmacotherapy, vol. 124, article 109849, 2020. View at: Publisher Site | Google Scholar
  104. Z. Tan, H. Liu, X. Song et al., “Honokiol post-treatment ameliorates myocardial ischemia/reperfusion injury by enhancing autophagic flux and reducing intracellular ROS production,” Chemico-Biological Interactions, vol. 307, pp. 82–90, 2019. View at: Publisher Site | Google Scholar
  105. H. Huang, S. Lai, Y. Luo et al., “Nutritional preconditioning of apigenin alleviates myocardial ischemia/reperfusion injury via the mitochondrial pathway mediated by notch1/hes1,” Oxidative Medicine and Cellular Longevity, vol. 2019, Article ID 7973098, 15 pages, 2019. View at: Publisher Site | Google Scholar

Copyright © 2020 Jian-Kang Mu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


More related articles

 PDF Download Citation Citation
 Download other formatsMore
 Order printed copiesOrder
Views2663
Downloads380
Citations

Related articles

Article of the Year Award: Outstanding research contributions of 2020, as selected by our Chief Editors. Read the winning articles.