Effects Of Pyrroloquinoline Quinone Research Articles

Effects of Pyrroloquinoline Quinone and Vitamin C on Diabetes Associated Testicular Dysfunction and Oxidative Damages in Testis of Streptozotocin-Induced Diabetic Mice: Histopathological Study

The aim of this study was to investigate the hitherto unknown potential of Pyrroloquinoline Quinone (PQQ) in regulating diabetes associated testicular dysfunctions and oxidative damages in testis of adult mice. Seven groups such as normoglycemic and PQQ treated controls; STZ-treated and STZ + PQQ treated (5, 10 and 20 mg/kg/day, separately) and STZ + Vit.C (50 mg/kg) were established.

Neuroprotective effects of pyrroloquinoline quinone against rotenone injury in primary cultured midbrain neurons and in a rat model of Parkinson's disease

Mitochondrial dysfunction and oxidative stress have been implicated in the pathogenesis of Parkinson's disease (PD). Pyrroloquinoline quinone (PQQ), a redox cofactor in the mitochondrial respiratory chain, has been reported to protect SH-SY5Y cells from cytotoxicity induced by rotenone, a mitochondrial complex I inhibitor. In this study, we aimed to investigate the neuroprotective effects of PQQ against rotenone injury in primary cultured midbrain neurons and in a rat model of Parkinson's disease. Pre-treatment with PQQ prevented cultured midbrain neurons from rotenone-induced apoptosis, restored mitochondrial membrane potential, inhibited intracellular reactive oxygen species (ROS) production, and affected microtubule depolymerization. On the other hand, intraperitoneal administration of PQQ exerted protective effects on rats that had received rotenone injection into the medial forebrain bundle through decreasing the apomorphine-evoked rotation, inhibiting neuronal loss and TH down-regulation in SNc, increasing the antioxidative ability, and regulating intracellular expressions of Ndufs1 and Ndufs 4. Silencing of Ndufs1 or Ndufs4 in cultured SH-SY5Y cells or midbrain neurons reduced the neuroprotective effects of PQQ. Overall, our results suggest that PQQ neuroprotection may be mediated by the inhibition of mitochondrial dysfunction and oxidative stress as well as by the gene modulation of Ndufs1 and Ndufs4.

Pyrroloquinoline quinone enhances the resistance to oxidative stress and extends lifespan upon DAF-16 and SKN-1 activities in C. elegans

Pyrroloquinoline quinone (PQQ) is linked to fundamental biological processes such as mitochondrial biogenesis and lipid metabolism. PQQ may also function as an essential micronutrient during animal development. Recent studies have shown the therapeutic potential of PQQ for several age-related diseases due to its antioxidant capacity. However, whether PQQ can promote longevity is unknown. Here, we investigate the effects of PQQ on oxidative stress resistance as well as lifespan modulation in Caenorhabditis elegans. We find that PQQ enhances resistance to oxidative stress and extends the lifespan of C. elegans at optimal doses. The underlying molecular mechanism involves the increased activities of the primary lifespan extension transcriptional factors DAF-16/FOXO, the conserved oxidative stress-responsive transcription factor SKN-1/Nrf2, and upregulation of daf-16, skn-1 downstream targets including sod-3, hsp16.2, gst-1 and gst-10. Our findings uncover a novel role of PQQ in longevity, supporting PQQ as a possible dietary supplement for overall health improvement.

The effect of pyrroloquinoline quinone on meiotic progression and metabolic parameters in diabetic mouse oocytes

The effect of pyrroloquinoline quinone on meiotic progression and metabolic parameters in diabetic mouse oocytes

Pyrroloquinoline quinone (PQQ) has potential to ameliorate streptozotocin-induced diabetes mellitus and oxidative stress in mice: A histopathological and biochemical study

Enhanced oxidative stress and hyperglycemia are associated with diabetes mellitus (DM). As pyrroloquinoline quinone (PQQ) is known to protect cells from oxidative stress, the present study was undertaken to reveal the hitherto unknown effects of PQQ in DM and associated problems in different tissues. Forty two mice were randomly divided into six groups. Group I receiving only citrate buffer served as the normal control, while group II animals were injected with citrate buffer and PQQ at 20 mg/kg for 15 days and served as test drug control. Animals of groups III–VI were rendered diabetic by single dose of streptozotocin (STZ, 150 mg/kg body weight), following which PQQ at a dose of 5, 10 and 20 mg/kg, was injected to the animals of group IV, V and VI respectively for 15 days. At the end, alterations in serum indices such as glucose, different lipids, insulin, amylase, urea, uric acid, serum glutamate pyruvate transaminase and serum glutamate oxaloacetate transaminase; tissue antioxidants and histopathological alterations in liver, kidney and pancreas were evaluated. STZ-treated animals developed oxidative stress as indicated by a significant increase in tissue lipid peroxidation (LPO) and lipid hydroperoxide, serum glucose, total cholesterol, triglyceride and urea, with a parallel decrease in the levels of serum insulin and tissue antioxidants. When diabetic animals received different doses of PQQ, these adverse effects were ameliorated. However, 20 mg/kg of PQQ appeared to be most effective. Findings revealed for the first time that PQQ has the potential to mitigate STZ-induced DM and oxidative damage in different organs of mice, suggesting that it may ameliorate diabetes mellitus and associated problems.

Pyrroloquinoline Quinone Decelerates Rheumatoid Arthritis Progression by Inhibiting Inflammatory Responses and Joint Destruction via Modulating NF-κB and MAPK Pathways

Pyrroloquinoline quinone (PQQ) is a naturally occurring redox cofactor that acts as an essential nutrient and antioxidant and has been reported to exert potent immunosuppressive effects. However, the therapeutically potential of PQQ on rheumatoid arthritis (RA) has not been explored. In the present study, the anti-inflammatory effects of PQQ were investigated in interleukin (IL)-1β-treated SW982 cells, a RA-like fibroblast-like synoviocytes (FLSs) injury model. Our observations showed that pretreatment with PQQ significantly inhibited the expression of matrix metalloproteinase (MMP)-1 and MMP-3 and suppressed the production of proinflammatory mediators such as TNF-α and IL-6 in IL-1β-treated SW982 cells. The nuclear translocation of nuclear factor kappa B (NF-κB) and the phosphorylation level of p65, p38, and JNK MAP kinase pathways were also inhibited by PQQ in IL-1β-stimulated SW982 cells. To further confirm the therapeutic effects of PQQ on RA in vivo, a collagen-induced arthritis (CIA) model was used. Mice treated with PQQ demonstrated marked attenuation of arthritic symptoms based on histopathology and clinical arthritis scores. These results collectively suggested that PQQ might be a promising therapeutic agent for alleviating the progress of RA.

Pyrroloquinoline quinone-conferred neuroprotection in rotenone models of Parkinson's disease.

Pyrroloquinoline quinone (PQQ), a redox cofactor in the mitochondrial respiratory chain, has proven to protect neurons against glutamate-induced damage both in vitro and in vivo. This study was aimed to investigate the possible neuroprotective effects of PQQ in rotenone-induced Parkinson's disease (PD) model. Pre-treatment with PQQ prevented cultured SH-SY5Y cells from rotenone-induced apoptosis, accompanied by modulation of apoptosis-related proteins (Bcl-2, Bax and Smac), restoration of the mitochondrial membrane potential, inhibition of intracellular reactive oxygen species (ROS) production, suppression of tyrosine residues nitration, and dopamine redistribution. PQQ also exerted protective effects in an in vivo PD model, which was created by rotenone injection into the medial forebrain bundle of rats. Co-injection with PQQ and rotenone improved the apomorphine-evoked rotation, decreased neuronal loss, increased the ROS-scavenging ability, regulated intracellular expressions of mitochondrial complex subunits (Ndufs1-4), tyrosine hydroxylase, and vesicular monoamine transporter 2. Taken together, our results collectively suggest that PQQ confers neuroprotection in rotenone-induced PD model probably through complex and multifaceted mechanisms, at least involving oxidative stress, mitochondrial integrity, and dopamine functions.

Pyrroloquinoline quinone (PQQ) producing Escherichia coli Nissle 1917 (EcN) alleviates age associated oxidative stress and hyperlipidemia, and improves mitochondrial function in ageing rats

BackgroundAgeing involves oxidative stress mediated by Reactive Oxygen Species (ROS) and mitochondrial dysfunction. The present work demonstrates the protective effect of PQQ producing EcN against rotenone induced mitochondrial oxidative stress and consequence of mitochondrial and cellular dysfunction in naturally ageing rat model. PQQ is a potent antioxidant molecule also known to stimulate mitochondrial biogenesis and function in mammals. MethodsFirstly, adult rats (16–18weeks old) were treated with rotenone (2.5mg/kg body weight; i.p.) daily for 28days along with PQQ (10mg/kg diet, daily) and modified probiotic EcN strains (108CFU twice weekly). Secondly, ageing rats (48–50weeks old) were gavaged with probiotic EcN strains (108CFU twice weekly) and PQQ (10mg/kg diet, daily) for 8months. ResultsPQQ producing EcN-5 treatment prevented rotenone induced hepatic oxidative stress and mitochondrial damage in rats as assessed by reduced lipid peroxidation (29%), elevated glutathione (GSH) content (43%), increased catalase (52%) and superoxide dismutase (52%) activities when compared to only rotenone treatment. Moreover, increased hepatic mitochondrial content (41%), peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) mRNA (25%) and mitochondrial Superoxide Dismutase (Mit-SOD) activity (94%) were also observed in EcN-5 treated rats. Rotenone treated rats did not exhibit gain in body weight, whereas rats co-treated with EcN-5 showed significant restoration in body weight gain. Furthermore, weekly administration of EcN-5 to naturally ageing rats for eight months resulted in significant reduction of oxidative stress in hepatic and colonic tissues (assessed by lipid peroxidation, GSH content and catalase and SOD enzyme activities) along with increase in hepatic mitochondrial enzyme activities (Mit-SOD and succinate dehydrogenase) and biogenesis, when compared to untreated rats. Additionally, these rats also exhibited reduced expression of fatty acid synthase (50%) and increased expression of acyl coenzyme oxidase (225%) genes in liver in contrast to untreated rats resulting in lowered triglyceride (13% & 13.5%) and cholesterol (21% & 27%) levels in plasma and liver, respectively. Increased levels of butyrate (93%), propionate (45%) and acetate (18%) were also found in colonic content of these rats. PQQ administered daily (supplemented in diet) exhibited more or less similar effect as weekly gavaged EcN-5 in both the experiments, which substantiate that these effects are mediated by PQQ. ConclusionThese results suggest that genetically modified EcN-5 can be used as a nutritional supplement which can reduce age related oxidative stress and hyperlipidemia. Furthermore, it also rejuvenates healthy mitochondria by stimulating mitochondrial biogenesis and metabolism.

Protective Effect of Pyrroloquinoline Quinone (PQQ) in Rat Model of Intracerebral Hemorrhage.

Pyrroloquinoline quinone (PQQ) has invoked considerable interest because of its presence in foods, antioxidant properties, cofactor of dehydrogenase, and amine oxidase. Protective roles of PQQ in central nervous system diseases, such as experimental stroke and spinal cord injury models have been emerged. However, it is unclear whether intracerebral hemorrhage (ICH), as an acute devastating disease, can also benefit from PQQ in experimental conditions. Herein, we examined the possible effect of PQQ on neuronal functions following ICH in the adult rats. The results showed that rats pretreated with PQQ at 10mg/kg effectively improved the locomotor functions, alleviated the hematoma volumes, and reduced the expansion of brain edema after ICH. Also, pretreated rats with PQQ obviously reduced the production of reactive oxygen species after ICH, probably due to its antioxidant properties. Further, we found that, Bcl-2/Bax, the important indicator of oxidative stress insult in mitochondria after ICH, exhibited increasing ratio in PQQ-pretreated groups. Moreover, activated caspase-3, the apoptotic executor, showed coincident alleviation in PQQ groups after ICH. Collectively, we speculated that PQQ might be an effective and potential neuroprotectant in clinical therapy for ICH.

Pyrroloquinoline quinone against glutamate-induced neurotoxicity in cultured neural stem and progenitor cells

Pyrroloquinoline quinone (PQQ), as a well-known redox enzyme cofactor, has been proven to play important roles in the regulation of cellular growth and development in mammals. Numerous physiological and medicinal functions of PQQ have so far been reported although its effect on neural stem and progenitor cells (NS/PCs) and the potential mechanism were even rarely investigated. In this study, the neuroprotective effects of PQQ were observed by pretreatment of NS/PCs with PQQ before glutamate injury, and the possible mechanisms were examined. PQQ stimulated cell proliferation and markedly attenuated glutamate-induced cell damage in a dose-dependent manner. By observing the nuclear morphological changes and flow cytometric analysis, PQQ pretreatment showed its significant effect on protecting NS/PCs against glutamate-induced apoptosis/necrosis. PQQ neuroprotection was associated with the decrease of intracellular reactive oxygen species (ROS) production, the increase of glutathione (GSH) levels, and the decrease of caspase-3 activity. In addition, pretreatment with PQQ also significantly enhanced the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in the NS/PCs exposed to glutamate. These results suggest that PQQ can protect NS/PCs against glutamate toxicity associated with ROS-mediated mitochondrial pathway, indicating a useful chemical for the clinical application of NS/PCs.

Effects of Pyrroloquinoline Quinone Disodium Salt Intake on the Serum Cholesterol Levels of Healthy Japanese Adults.

Pyrroloquinoline quinone (PQQ) is a water-soluble quinone compound that has a strong anti-oxidant capacity. A previous study in rats fed a PQQ-depleted diet showed that elevated levels of serum triglyceride (TG) decreased after PQQ supplementation. However, there is only one study reporting the effects of PQQ on serum lipid levels, such as those of TG and cholesterol, in humans. In this study, the effects of PQQ disodium salt (BioPQQ™) on serum TG and cholesterol levels in humans after 6 and 12 wk of treatment at an oral dosage of 20 mg/d were examined. This trial was conducted according to a randomized, placebo-controlled, double-blinded protocol. A total of 29 healthy Japanese adults, ranging from 40 to 57 y old, with normal to moderately high TG levels (110-300 mg/dL) as measured by a recent blood examination, were included in this study. In eleven volunteers out of 29, serum low-density lipoprotein cholesterol (LDL-chol) levels at baseline were high (≥140 mg/dL). After 12 wk, the mean serum TG levels had not changed; however, a marginally significant decrease in the mean LDL-chol (from 136.1 to 127.0 mg/dL) was observed in the PQQ group. In the stratification analysis of the high LDL-chol subgroup (baseline LDL-chol level ≥140 mg/dL), the mean LDL-chol levels decreased significantly from the baseline values in the PQQ group compared to the placebo group. Our study findings suggest that PQQ suppressed the LDL-chol level, which is an important finding, because a high level of this lipid is a risk factor for various lifestyle-related diseases.

Pyrroloquinoline quinone (PQQ) inhibits lipopolysaccharide induced inflammation in part via downregulated NF-κB and p38/JNK activation in microglial and attenuates microglia activation in lipopolysaccharide treatment mice.

Therapeutic strategies designed to inhibit the activation of microglia may lead to significant advancement in the treatment of most neurodegenerative diseases. Pyrroloquinoline quinone (PQQ) is a naturally occurring redox cofactor that acts as an essential nutrient, antioxidant, and has been reported to exert potent immunosuppressive effects. In the present study, the anti-inflammatory effects of PQQ was investigated in LPS treated primary microglia cells. Our observations showed that pretreatment with PQQ significantly inhibited the production of NO and PGE2 and suppressed the expression of pro-inflammatory mediators such as iNOS, COX-2, TNF-a, IL-1b, IL-6, MCP-1 and MIP-1a in LPS treated primary microglia cells. The nuclear translocation of NF-κB and the phosphorylation level of p65, p38 and JNK MAP kinase pathways were also inhibited by PQQ in LPS stimulated primary microglia cells. Further a systemic LPS treatment acute inflammation murine brain model was used to study the suppressive effects of PQQ against neuroinflammation in vivo. Mice treated with PQQ demonstrated marked attenuation of neuroinflammation based on Western blotting and immunohistochemistry analysis of Iba1-against antibody in the brain tissue. Indicated that PQQ protected primary cortical neurons against microglia-mediated neurotoxicity. These results collectively suggested that PQQ might be a promising therapeutic agent for alleviating the progress of neurodegenerative diseases associated with microglia activation.

Involvement of ERK1/2 pathway in neuroprotective effects of pyrroloquinoline quinine against rotenone-induced SH-SY5Y cell injury

Pyrroloquinoline quinone (PQQ), a redox cofactor in the mitochondrial respiratory chain, has been shown to protect neurons against glutamate-induced damage both in vitro and in vivo. In this study, specific inhibitors to each of the mitochondrial complexes were used to find out which reactive oxygen species (ROS)-generating sites could be affected by PQQ. Then we established an in vitro model of Parkinson’s disease (PD) by exposing cultured SH-SY5Y dopaminergic cells to rotenone, a complex I inhibitor. The neuroprotective effects of PQQ were observed by pretreatment of SH-SY5Y cells with PQQ before rotenone injury, and the possible involvement of certain signaling pathways were investigated. PQQ pretreatment prevented SH-SY5Y cells from rotenone-induced apoptosis in a concentration-dependent manner. PQQ neuroprotection was associated with inhibition of intracellular ROS production, modulation of the expression of apoptosis-related Bcl-2 and Bax, and regulation of the level of superoxide dismutase, glutathione, and malondialdehyde. Meanwhile, PQQ up-regulated the gene expression of Ndufs 1, 2, and 4 (complex I subunits), and increased mitochondrial viability and mitochondrial DNA content. Furthermore, PQQ pretreatment activated ERK1/2 phosphorylation in rotenone-injured SH-SY5Y cells, while ERK1/2 inhibition suppressed PQQ neuroprotection. All the results suggested that PQQ could protect SH-SY5Y cells against rotenone injury by reducing ROS production and maintaining mitochondrial functions through activation of ERK1/2 pathway.

Pyrroloquinoline Quinone Induces Cancer Cell Apoptosis via Mitochondrial-Dependent Pathway and Down-Regulating Cellular Bcl-2 Protein Expression.

Pyrroloquinoline quinone (PQQ) has been reported as a promising agent that might contribute to tumor cell apoptosis and death, yet little is known on its mechanisms. In current study, the effect of PQQ on cell proliferation and mitochondrial-dependent apoptosis were examined in 3 solid tumor cell lines (A549, Neuro-2A and HCC-LM3). PQQ treatment at low to medium dosage exhibited potent anti-tumor activity on A549 and Neuro-2A cells, while had comparably minimal impact on the viabilities of 2 human normal cell lines (HRPTEpiC and HUVEC). The apoptosis of the 3 tumor cell lines induced by PQQ were increased in a concentration-dependent manner, which might be attributed to the accumulation of intracellular reactive oxygen species (ROS), decline in ATP levels and dissipation of mitochondrial membrane potential (MMP), in conjunction with down-regulation of Bcl-2 protein expression, up-regulation of activated caspase-3, and disturbed phosphorylated MAPK protein levels. PQQ induced tumor cells apoptosis was significantly alleviated by pan-caspase inhibitor Z-VAD-FMK. The present work highlights the potential capability of PQQ as an anti-tumor agent with low toxicity towards normal cells through activating mitochondrial-dependent apoptosis pathways, and warrants its development for cancer therapy.

Pyrroloquinoline quinone prevents MK-801-induced stereotypical behavior and cognitive deficits in mice

Pyrroloquinoline quinone (PQQ), an essential nutrient, antioxidant, redox modulator, and nerve growth factor, prevents cognitive deficits associated with oxidative stress-induced neurodegeneration. Previous molecular imaging studies also demonstrate that PQQ binds to N-methyl d-aspartate (NMDA) receptors. In this study, we investigated the effects of PQQ on stereotypical behaviors and cognitive deficits induced by MK-801, a non-competitive NMDA antagonist used to model schizophrenia. Mice were given repeated injections of MK-801 (0.5mg/kg/d) and PQQ (0.2, 2.0, or 20μg/kg/d) for 60 days. Behavior was evaluated using a variety of motor, social, and cognitive tests. We found that PQQ administration significantly attenuated MK-801-induced increases in stereotypical behavior and ataxia, suggesting a protective role of PQQ against MK-801-induced neuronal dysfunction and psychiatric disorders. Future studies are necessary to elucidate the underlying mechanisms of PQQ.

Pyrroloquinoline quinone inhibits oxygen/glucose deprivation-induced apoptosis by activating the PI3K/AKT pathway in cardiomyocytes

The purposes of this study were to examine the protective effect of pyrroloquinoline quinone (PQQ) on oxygen/glucose deprivation (OGD)-induced injury to H9C2 rat cardiomyocytes and to investigate the mechanism. Using H9C2 cells cultured in vitro, we examined changes in cell viability with an MTT assay at 12, 24, and 48h after injury induced by OGD. Various concentrations of PQQ (1, 10, and 100μM) were added, and the effect of PQQ on cell viability after OGD was assessed using the MTT assay. Thus, the optimal concentration of PQQ for the protection of cardiomyocytes against oxygen and glucose deprivation injury was determined. We also used flow cytometry analysis to examine the effect of PQQ on H9C2 cells with OGD-induced injury. The molecular probe 2',7'-dichlorofluorescin diacetate was used to label the H9C2 cells, and flow cytometry was used to detect the effect of PQQ on reactive oxygen species (ROS) content. After labeling the H9C2 cells using a mitochondrial green fluorescent probe (Mito-Tracker Green), we measured the change in the mitochondrial content of PQQ-treated H9C2 cells. Western blotting was used to examine the effect of PQQ on the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in the H9C2 cells. The results of the MTT assay showed that 48h of OGD significantly injured the H9C2 cells (p<0.01) and that treatment with 100μM PQQ effectively decreased the level of OGD-induced injury (p<0.01). The results of the flow cytometry analysis showed that PQQ significantly reduced apoptosis in H9C2 cells subjected to OGD (p<0.05). In addition, OGD significantly increased the ROS level in H9C2 cells (p<0.01), and PQQ significantly inhibited this increase (p<0.05). The results of the Mito-Tracker Green staining suggested that PQQ effectively inhibited the decrease in mitochondrial content caused by OGD (p<0.05). Western blot analysis showed that PQQ partially reversed the decrease in Akt phosphorylation that was caused by OGD (p<0.05). PQQ treatment dose-dependently protects H9C2 cells from OGD-induced injury by reducing apoptosis, decreasing intracellular ROS levels, and rescuing the OGD-induced decrease in mitochondrial content. The protective effect of PQQ may be related to its effects on the PI3K/Akt pathway.

Effect of pyrroloquinoline quinone on neuropathic pain following chronic constriction injury of the sciatic nerve in rats

Pyrroloquinoline quinone PQQ is a naturally occurring redox cofactor that acts as an essential nutrient, antioxidant, and redox modulator. PQQ has been demonstrated to oxidize the redox modulatory site of N-methyl-d-aspartic acid (NMDA) receptors. Such agents are known to be neuroprotective in experimental stroke models. However, there is not report about the therapeutic effect of PQQ on neuropathic pain. We tested the effects of oral administration of PQQ on neuropathic pain of rats with chronic constriction injury (CCI) of the sciatic nerve. The repeated oral administration of PQQ (20 and 40mg/kg, once a day for 4 weeks, from day 1 after the injury) attenuated both thermal and mechanical hyperalgesia, and also attenuated the muscle atrophy. The anti-hyperalgesic activity of PQQ was associated with a significant reduction of pro-inflammatory mediators such as tumor necrosis factor alpha (TNF-α) and lipid peroxide malondialdehyde (MDA) levels. In the present investigation, PQQ is shown to have analgesic effect which was found in the first time, probably through reducing the release of pro-inflammatory mediator and inhibiting oxidative stress.

Effects of Oral Supplementation with Pyrroloquinoline Quinone on Stress, Fatigue, and Sleep

Seventeen adult male and female subjects participated in a clinical trial using an open-label trial to evaluate the effectiveness of pyrroloquinoline quinone (PQQ) on stress, fatigue, quality of life and sleep. They ingested 20 mg of PQQ daily for 8 weeks. Changes in stress, fatigue, quality of life measures and sleep were evaluated using various inventories and questionnaires. For example, the results of the Profile of Mood States-Short Form revealed that all six measures of vigor, fatigue, tension-anxiety, depression, anger-hostility and confusion were significantly improved following PQQ administration compared with scores for those measures before administration of PQQ. Measures for quality of life, appetite, sleep, obsession and pain, also improved significantly. The results of the Oguri-Shirakawa-Azumi Sleep Inventory (Middle Aged and Aged version) showed significant improvement in sleepiness at awakening, sleep onset and maintenance, and sleep duration. For validation, the Pittsburgh Sleep Quality Index Japanese version also showed significant improvement in sleep-related behavior. Furthermore, the changes in these global scores were correlated with changes in the cortisol awakening response (R = -0.55), i.e. the effects of PQQ on improvement of sleep quality are supported by a biomarker.Keywords: Pyrroloquinoline quinone, stress, fatigue, quality of life, sleep

Protective effect of pyrroloquinoline quinine on cartilage in rabbit osteoarthritis models

Objective To study the protective effect of pyrroloquinoline quinone (PQQ) on cartilate in rabbit osteoarthritis models.Methods Thirty-six 6-month-old Japanese white rabbits were randomly divided into experimental group,control group and sham-operation group ( 12 rabbits in each group).The osteoarthritis models at the right knee in experimental group and control group were established followed by the Huhh method.Animals in the experimental group were given intra-articular injection of 1 × 104 μmol/L PQQ (0.2 ml/kg body weight),3 days a week for 6 weeks.The same volume of saline was delivered in the control group.There was no special treatment on animals in the sham-operation group.Animals were sacrificed 6 weeks after anteroposterior X-ray evaluation.HE staining,type Ⅱ collagen immunohistochemical staining,chondrocyte apoptosis [TdT-mediated dUTP nick end labeling (TUNEL)] detection,and electron microscopy observation of mitochondrion changes in cartilage were done.Results Kellgren-Lawrance score in experimental group,control group and sham-operation group was 1.49 ±0.45,5.69 ± 1.08,and 0.28 ± 0.06,respectively,P ＜ 0.05.Degeneration changes of femoral condyle were alleviated by PQQ (JP score 1.46 ± 0.42,2.75 ± 0.60,0.08 ± 0.04,P ＜0.05 ).Mankin scores were 2.68 ± 0.86,6.95 ±1.46 and 0.25 ± 0.06,P ＜ 0.05 ; and number of apoptotic chondrocytes was ( 5.60 ± 1.20) ％,( 35.30 ±4.90) ％,(0.70 ± 0.30 ) ％,P ＜ 0.05.More mitochondrials were observed under an electron microscope (3.40 ± 0.68,1.24 ± 0.45,and 6.40 ± 1.20,P＜0.05 ).Well structured type Ⅱ collagen fibers were observed in the experimental group.Conclusion Intra-articular injection of PQQ can protect the cartilage during osteoarthritis development by alleviating the structure and function damage of the cartilage and promoting its metabolism and self-repair capacity.PQQ may take the function by protecting mitochondria in chondrocytes. Key words: Osteoarthritis; Pyrrololine quinone; Chondrocyte

Pyrroloquinoline Quinone (PQQ) and Indicators of Antioxidant Potential, Inflammation and Metabolism in Humans

Pyrroloquinoline quinone (PQQ) improves parameters related to energy metabolism in animals, which involve interactions with cell signaling important to mitochondrial function. However, little is known about responses to PQQ in humans. Using a crossover study design, 10 subjects ingested PQQ and were examined in two studies at 2 to 3 daily intervals. Plasma antioxidant potential (TBARS and TRAP measurements), inflammation (plasma C‐reactive protein and IL‐6), and standard clinical indices were measured, including urinary metabolites. In addition, PQQ clearance was investigated. Data suggested that PQQ is absorbed in the upper intestine with a relatively slow clearance from the plasma pool. Measurement of plasma antioxidant activity was highly correlated with plasma PQQ concentrations. Decreased levels of plasma C‐reactive protein and IL‐6 were also observed (~ 20 mg PQQ/day X 3 d; p &lt;0.01). No changes in clinical indices were observed. However, exposure to PQQ (10–20 mg PQQ/day X 3 d) altered the distribution of mitochondrial‐related urinary metabolites in urine using as assessed by the NMR. It was concluded that the effects of PQQ in humans could be observed with a short‐term exposure at levels easily obtained in commercial supplements. Supported by Mitsubishi Gas and Chemical Co. and the Center for Health Related Research at UCD.