PQQ

BACKGROUND: Alcohol abuse is one of the most common causes of mortality worldwide. This study aimed to investigate the efficacy of a treatment in reducing circulating ethanol and oxidative stress biomarkers. METHODS: Twenty wine-drinking subjects were investigated in a randomized controlled, single-blind trial (ClinicalTrials.gov. Identifier: NCT06548503; Ethical Committee of the University of Padova (HEC-DSB/12-2023) to evaluate the effect of the intake of a product containing silymarin, pyrroloquinoline quinone sodium salt, and myricetin (referred to as Si.Pi.Mi. for this project) on blood alcohol, ethyl glucuronide (EtG: marker for alcohol consumption) and markers of oxidative stress levels (Reactive Oxygen Species-ROS, Total Antioxidant Capacity-TAC, CoQ10, thiols redox status, 8-isoprostane, NO metabolites, neopterin, and uric acid). The effects of the treatment versus placebo were evaluated acutely and after 1 week of supplementation in blood and/or saliva and urine samples. RESULTS: Si.Pi.Mi intake reduced circulating ethanol after 120 min (-33%). Changes in oxidative stress biomarkers, particularly a TAC (range +9-12%) increase and an 8-isoprostane (marker of lipidic peroxidation) decrease (range -22-27%), were observed too. CONCLUSION: After the administration of Si.Pi.Mi, the data seemed to suggest a better alcohol metabolism and oxidative balance in response to wine intake. Further verification is requested.

OBJECTIVES: To assess the impact of medium-term supplementation with dihydrogen and pyrroloquinoline quinone (PQQ) on mitochondrial biomarkers, brain metabolism, and cognition in elderly individuals diagnosed with mild cognitive impairment. DESIGN: A parallel-group, randomized, placebo-controlled, double-blind experimental design, maintaining a 1:1 allocation ratio between the experimental group (receiving the dihydrogen-producing minerals and PQQ) and the control group (receiving the placebo) throughout the trial. SETTING AND PARTICIPANTS: Thirty-four elderly individuals with mild cognitive impairment (mean age 71.9 ± 3.8 years; 28 females) voluntarily provided written consent to participate in this trial. Participants were assigned in a double-blind parallel-group design to receive either a dihydrogen-PQQ mixture (Alpha Hope®, CalerieLife, Irvine, CA) or placebo twice daily for a 6-week intervention period. METHODS: The primary endpoint was the change in serum brain-derived neurotrophic factor (BDNF) from baseline to the 6-week follow-up; secondary outcomes included cognitive function indices, specific metabolites in brain tissue, brain oxygenation, and the prevalence and severity of side effects. Interaction effects (time vs. intervention) were evaluated using two-way ANOVA with repeated measures and Friedman's 2-way ANOVA by ranks, for normally distributed data with homogeneous variances and non-homogeneous variances, respectively. RESULTS: Dihydrogen-PQQ resulted in a significant elevation in serum BDNF levels at the six-week follow-up (P = 0.01); conversely, no changes in BDNF levels were observed in the placebo group throughout the study duration (P = 0.27). A non-significant trend in the impact of interventions on BDNF levels was observed (treatment vs. time interaction, P = 0.14), suggesting a tendency for dihydrogen-PQQ to upregulate BDNF levels compared to the placebo. A significant interaction effect was observed for the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores in the orientation domain (P = 0.03), indicating the superiority of dihydrogen-PQQ over placebo in enhancing this cognitive aspect. Cerebral oxygenation satura

Brain function is important for a good quality of life. Pyrroloquinoline quinone disodium salt (PQQ) has been proven to improve brain function and cognition in older adults (above 45 years). In this double-blind, placebo-controlled study, we investigated the effects of PQQ on cognitive function in adults aged between 20 and 65 years. PQQ (20 mg per day) was administered for 12 weeks to the participants. After 12 weeks, the participants showed improvements in composite memory and verbal memory. A further age-stratified analysis was performed. In younger adults (aged 20-40 years), PQQ improved cognitive function (cognitive flexibility, processing speed, and execution speed) after 8 weeks. Only older adults (aged 41-65 years) showed improvements in complex and verbal memory after 12 weeks. In the logistic regression analysis that included the results of all cognitive tests, the changes due to PQQ intake were observed at 8 and 12 weeks in the young and old groups, respectively.

BACKGROUND: Cognitive dysfunctions are increasing alarmingly around the world, and researchers are exploring preventive measures for improving brain performance. Pyrroloquinoline quinone (PQQ), a naturally occurring coenzyme in foods, exhibits potent antioxidant activity, and improves diverse functions which include mitochondrial activation, growth, repair, protection of nerve cells by increased expression of nerve growth factor (NGF) and NGF receptors; and suppression of fibril formation and aggregation of amyloid β. OBJECTIVE: This randomized, double-blind, placebo-controlled, parallel-group clinical investigation (RCT) evaluated the efficacy and safety of PQQ disodium salt powder (mnemoPQQ®) for improved cognitive function after 12 weeks of supplementation in healthy Japanese male and female (age 40 to <80 Y). METHODS: 64 healthy subjects were randomly assigned to receive either mnemoPQQ® (PQQ disodium salt: 21.5 mg/day) or a placebo over a period of 12 weeks. The efficacy of mnemoPQQ® on cognitive performance (memory, attention, judgment, and cognitive flexibility) was examined using Cognitrax as the primary outcome (primary endpoint), and forgetfulness questionnaire (DECO: Deterioration Cognitive Observee) and Mini-Mental State Examination-Japanese (MMSE-J) as the secondary outcome (secondary endpoint). RESULTS: A total of 58 subjects (placebo = 31; Age = 70.91 ± 3.06 Y; mnemoPQQ® group = 27; Age = 72.10 ± 3.77 Y) completed the study over a period of 12 weeks of supplementation. Significant improvements were observed on the Cognitrax's cognitive function domain score on "composite memory", "verbal memory", "reaction time", "complex attention", "cognitive flexibility", "executive function", and "motor speed" in the mnemoPQQ® group as compared to the placebo group. The DECO and the MMSE-J scores were also significantly improved in the mnemoPQQ® group. No adverse events were observed. CONCLUSIONS: Study demonstrates that supplementation of PQQ disodium salt is useful in improving memory, attention, judgment, and cognitive function, in middle-aged to elderly population, who feel they have become more forgetful because of aging.

Objective: Pyrroloquinoline quinone (PQQ) is a novel supplement involved in processes such as mitochondrial biogenesis and cellular energy metabolism. Since endurance exercise and PQQ exhibit similar mechanisms for mitochondrial biogenesis, it is plausible that PQQ may have ergogenic value. Therefore, the purpose of this study was to examine the effects of a six-week endurance exercise training program on mitochondrial biogenesis and aerobic performance in non-endurance-trained males.Methods: Twenty-three males were randomized to consume 20 mg/day of PQQ or placebo (PLC). Both groups followed a supervised six-week endurance exercise training program. Body composition was assessed by dual-energy-x-ray-absorptiometry (DEXA). Aerobic exercise performance and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a biochemical marker for mitochondrial biogenesis, were assessed before and after the six-week endurance training/supplementation program.Results: There were no significant differences between groups in aerobic performance after endurance-training (p > 0.05). However, there were significant improvements in peak oxygen consumption (VO2peak) and total exercise test duration after endurance-training, irrespective of group (p < 0.05). The PQQ group had a significant increase in PGC-1α protein levels from baseline to post endurance training compared to PLC (p < 0.05). Furthermore, the PQQ group had higher PGC-1α protein levels after 6 weeks of endurance training compared to PLC (p < 0.05).Conclusions: Supplementation of PQQ does not appear to elicit any ergogenic effects regarding aerobic performance or body composition but appears to impact mitochondrial biogenesis by way of significant elevations in PGC-1α protein content.

Pyrroloquinoline quinone (PQQ) is a quinone compound originally identified in methanol-utilizing bacteria and is a cofactor for redox enzymes. At the Meeting of the International Society on Oxygen Transport to Tissue (ISOTT) 2014, we reported that PQQ disodium salt (BioPQQ™) improved cognitive function in humans, as assessed by the Stroop test. However, the physiological mechanism of PQQ remains unclear. In the present study, we measured regional cerebral blood flow (rCBF) and oxygen metabolism in prefrontal cortex (PFC), before and after administration of PQQ, using time-resolved near-infrared spectroscopy (tNIRS). A total of 20 healthy subjects between 50 and 70 years of age were administered BioPQQ™ (20 mg) or placebo orally once daily for 12 weeks. Hemoglobin (Hb) concentration and absolute tissue oxygen saturation (SO2) in the bilateral PFC were evaluated under resting conditions using tNIRS. We found that baseline concentrations of hemoglobin and total hemoglobin in the right PFC significantly increased after administration of PQQ (p < 0.05). In addition, decreases in SO2 level in the PFC were more pronounced in the PQQ group than in the placebo group (p < 0.05). These results suggest that PQQ causes increased activity in the right PFC associated with increases in rCBF and oxygen metabolism, resulting in enhanced cognitive function.

The protective effects of dietary pyrroloquinoline quinone disodium (PQQ.Na2) supplementation against oxidized sunflower oil-induced oxidative stress and liver injury in laying hens were examined. Three hundred and sixty 53-week-old Hy-Line Gray laying hens were randomly allocated into one of the five dietary treatments. The treatments included: (1) a diet containing 2% fresh sunflower oil; (2) a diet containing 2% thermally oxidized sunflower oil; (3) an oxidized sunflower oil diet with 100 mg/kg of added vitamin E; (4) an oxidized sunflower oil diet with 0.08 mg/kg of PQQ.Na2; and (5) an oxidized sunflower oil diet with 0.12 mg/kg of PQQ.Na2. Birds fed the oxidized sunflower oil diet showed a lower feed intake compared to birds fed the fresh oil diet or oxidized oil diet supplemented with vitamin E (P=0.009). Exposure to oxidized sunflower oil increased plasma malondialdehyde (P<0.001), hepatic reactive oxygen species (P<0.05) and carbonyl group levels (P<0.001), but decreased plasma glutathione levels (P=0.006) in laying hens. These unfavorable changes induced by the oxidized sunflower oil diet were modulated by dietary vitamin E or PQQ.Na2 supplementation to levels comparable to the fresh oil group. Dietary supplementation with PQQ.Na2 or vitamin E increased the activities of total superoxide dismutase and glutathione peroxidase in plasma and the liver, when compared with the oxidized sunflower oil group (P<0.05). PQQ.Na2 or vitamin E diminished the oxidized sunflower oil diet induced elevation of liver weight (P=0.026), liver to BW ratio (P=0.001) and plasma activities of alanine aminotransferase (P=0.001) and aspartate aminotransferase (P<0.001) and maintained these indices at the similar levels to the fresh oil diet. Furthermore, oxidized sunflower oil increased hepatic DNA tail length (P<0.05) and tail moment (P<0.05) compared with the fresh oil group. Dietary supplementation of PQQ.Na2 or vitamin E decreased the oxidized oil diet induced DNA tail length and tail moment to the basal levels in fresh oil diet. These results indicate that PQQ.Na2 is a potential antioxidant and is as effective against oxidized oil-related liver injury in laying hens as vitam

Pyrroloquinoline quinone (PQQ) is a quinone compound first identified in 1979. It has been reported that rats fed a PQQ-supplemented diet showed better learning ability than controls, suggesting that PQQ may be useful for improving memory in humans. In the present study, a randomized, placebo-controlled, double-blinded study to examine the effect of PQQ disodium salt (BioPQQ™) on cognitive functions was conducted with 41 elderly healthy subjects. Subjects were orally given 20 mg of BioPQQ™ per day or placebo, for 12 weeks. For cognitive functions, selective attention by the Stroop and reverse Stroop test, and visual-spatial cognitive function by the laptop tablet Touch M, were evaluated. In the Stroop test, the change of Stroop interference ratios (SIs) for the PQQ group was significantly smaller than for the placebo group. In the Touch M test, the stratification analyses dividing each group into two groups showed that only in the lower group of the PQQ group (initial score<70), did the score significantly increase. Measurements of physiological parameters indicated no abnormal blood or urinary adverse events, nor adverse internal or physical examination findings at any point in the study. The preliminary experiment using near-infrared spectrometry (NIRS) suggests that cerebral blood flow in the prefrontal cortex was increased by the administration of PQQ. The results suggest that PQQ can prevent reduction of brain function in aged persons, especially in attention and working memory.

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.

The potential benefits of supplementing pyrroloquinoline quinone disodium (PQQ·Na2) in the diet of broiler chicks were explored. We first examined the effect of different levels of dietary PQQ·Na2 on growth performance, carcass characteristics, and plasma biochemical parameters (trial 1). A total of 490 1-day-old male Arbor Acres (AA) broiler chicks were randomly divided into 5 dietary groups supplemented with 0, 0.05, 0.1, 0.2, or 0.4 mg PQQ·Na2/kg feed. As the 0.2 mg/kg PQQ·Na2 supplement gave the best performance, we then investigated whether this level of PQQ·Na2 influenced the redox status of plasma samples and mitochondrial-related metabolism (trial 2). A total of 120 1-day-old male AA chicks were randomly divided into 2 groups supplemented with 0 or 0.2 mg PQQ·Na2/kg diet. In trial 1, birds fed a diet containing 0.2 mg PQQ·Na2/kg showed lower feed conversion ratio compared with those fed the control diet in the overall study (d 1 to 42, P=0.039). Breast muscle yield (d 42) increased quadratically in response to dietary PQQ·Na2 supplementation (P=0.021). Analysis of plasma biochemical parameters revealed that feeding broiler chicks with ≤0.4 mg/kg PQQ·Na2 did not cause adverse health effects. In trial 2, birds fed 0.2 mg/kg PQQ·Na2 again showed improved feed efficiency than the control birds in the grower and overall phases (P=0.038 and 0.016, respectively). In addition, dietary PQQ·Na2 supplementation resulted in a higher anti-oxidative capacity (P=0.001), lower redox potential (P=0.008), and higher hepatic citrate synthase activity (P=0.002). In contrast, no difference in hepatic mitochondrial DNA copy number was observed between the 2 experimental groups (P>0.1). These results indicate that PQQ·Na2 is a potentially effective feed additive for improving feed efficiency, stimulating breast muscle development, and maintaining redox status in broiler chicks. Enhancement of mitochondria efficiency, rather than modulating mitochondria numbers, may underlie the growth-promoting effect of PQQ·Na2. © 2015 Poultry Science Association Inc.

This study optimized stabilizer type and concentration, and screened natural antioxidant combinations to enhance the stability of a protein beverage fortified with vitamins A, D2, and D3. Three stabilizers-carrageenan, sodium carboxymethyl cellulose (Na-CMC), and microcrystalline cellulose (MCC)-were evaluated at 0.15-0.45% (w/v) during accelerated storage at 45 °C for 21 days. Stability was assessed using Turbiscan analysis, pH, particle size, Zeta potential, and color. MCC at 0.35% demonstrated the best stabilization, with minimal changes in Turbiscan Stability Index, particle size, and Zeta potential. Five natural antioxidants-dl-α-tocopherol, vitamin C, epigallocatechin gallate (EGCG), tea polyphenols (TP), and pyrroloquinoline quinone (PQQ)-were screened for vitamin protection using HPLC. Although vitamin C exhibited the highest in vitro DPPH radical scavenging activity (IC50 = 3.44 μg/mL), TP and EGCG provided superior protection of vitamins in the emulsion system. A synergistic antioxidant blend of EGCG, TP, and dl-α-tocopherol in a 4:4:2 mass ratio was identified as optimal, significantly prolonging vitamin retention over 21 days and yielding the longest predicted shelf-life (>84 days at 25 °C). These findings provide a practical formulation strategy for enhancing the physical and nutritional stability of functional protein beverages.

As the global population ages rapidly, delaying and preventing age-related diseases have become urgent priorities in public health and biomedical research. During aging, mitochondrial dysfunction is a core molecular hallmark and a common pathogenic mechanism underlying multiple age-related disorders. Age-related mitochondrial dysfunction typically manifests as diminished metabolic capacity, impaired organelle renewal, and disrupted redox homeostasis. These factors interact to form a feedback loop constraining mitochondrial adaptability. Specifically, the interdependent decline in NAD+ availability, impaired mitochondrial biogenesis, and excessive oxidative stress render single-pathway interventions ineffective in mitigating systemic functional impairments triggered by aging. To address this complex mechanism, this review presents a novel tri-axis anti-aging model encompassing three key compounds: nicotinamide mononucleotide/nicotinamide riboside (NMN/NR), pyrroloquinoline quinone (PQQ), and l-ergothioneine (EGT). Within this framework, NMN/NR serves as a broad NAD+-dependent regulator of mitochondrial homeostasis, with its most immediate effects on metabolic activation, while PQQ and EGT may further strengthen mitochondrial remodeling and redox resilience, respectively. While each compound has distinct functional emphases, they are highly mechanistically coupled, collectively forming a closed-loop network regulating mitochondrial number, function, and homeostasis. This review synthesizes preclinical and emerging clinical evidence supporting the standalone or combined use of NMN/NR, PQQ, and EGT across various diseases. Collectively, by conceptualizing mitochondrial aging as a systemic imbalance rather than isolated molecular defects, this paper highlights a three-axis model of NMN/NR, PQQ, and EGT. This framework offers a theoretical foundation for mitochondrial-targeted anti-aging interventions while laying the groundwork for future clinical research, nutritional interventions, and the development of multi-target combination strategies.

Pyrroloquinoline quinone (PQQ) is a redox cofactor derived from prokaryotes that participates in various biological processes involving dehydrogenase enzymes. Previous field trials identified a PQQ-producing endophyte, Burkholderia seminalis 869T2, which enhances banana growth and reduces Fusarium wilt incidence from 24.5% to 3.4%. While more recent studies have confirmed its agricultural benefits across multiple plant species, the underlying molecular mechanisms remain unclear. Here, integrated omics and imaging mass spectrometry were employed to investigate the role of PQQ in planta. Our results indicate that PQQ achieves these outcomes by modulating key aspects of plant energy metabolism, including the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and NAD/NADP pathways. In addition, PQQ appears to influence phytohormone signalling pathways and trigger systemic plant resistance. Consistent with these molecular responses, exogenous PQQ enhanced root and shoot development and improved resistance to Fusarium infection. Collectively, these findings indicate that the endophyte functions as a biostimulant through PQQ production, coordinating plant metabolism and defence to counter pathogen invasion. This study provides mechanistic insight into plant-endophyte mutualism and highlights the potential of both PQQ and PQQ-producing endophytes as biostimulants for sustainable agricultural applications. © 2026 The Author(s). Physiologia Plantarum published by John Wiley & Sons Ltd on behalf of Scandinavian Plant Physiology Society.

Erratum in Aging Cell. 2026 Jul;25(7):e70598. doi: 10.1111/acel.70598. Environmental antibiotic pollution is an underexplored contributor to gut aging and chronic intestinal diseases. We provide evidence that chronic exposure to enrofloxacin (ENR), a commonly detected veterinary antibiotic, accelerates gut aging and disease progression through a mitochondria-centered mechanism. In a population-based cross-sectional analysis, recent antibiotic use was associated with increased biological age and a higher risk of diarrhea in middle-aged and older adults, supporting a link between antibiotic exposure and impaired gut health and aging processes. Using zebrafish and intestinal epithelial cell models, we demonstrate that low-dose ENR exposure impairs intestinal function, characterized by increased permeability, reduced mucus secretion, tight junction disruption, and chronic inflammation. Multi-omics profiling revealed that ENR induced gut microbial dysbiosis, reduced metabolic diversity, and intestinal hypoxia. Mitochondrial dysfunction, particularly impaired oxidative phosphorylation, was identified as the key driver of epithelial damage. Remarkably, treatment with pyrroloquinoline quinone, a mitochondrial-targeted antioxidant, reversed ENR-induced mitochondrial injury, restored intestinal integrity, reduced inflammation, and partially normalized the microbiome. Stratified analyses in the human cohort showed that higher gut microbiota-related diet quality and antioxidant capacity mitigated antibiotic-associated aging and diarrhea risk. These findings highlight mitochondrial protection and microbiota optimization as promising therapeutic strategies. © 2026 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.

The Pyrroloquinoline Quinone (PQQ) is a quinone molecule that is redox active and has important health consequences for people. Several preclinical studies reveal the anticancer property of PQQ molecule by different molecular pathways. but there is a lack of clinical studies evaluating this drug in oncology. Clinical investigations have only investigated PQQ as a dietary supplement, disodium salt. The known safety profile and availability of standardized formulations provide the opportunity to advance PQQ into translational research in cancer. Future initiatives will involve testing in animal tumor models, analyzing possible synergistic effects with existing medicines, improving formulations to boost absorption, and discovering biomarkers to help patient selection.

Despite their miniscule mass, microgravity has been shown to impose physiological stresses on bacteria, leading to altered gene regulation and metabolic output in unpredictable ways. Changes in metabolic output can ultimately impact the production of bacterial secondary metabolites. While a few studies have explored the changes in bacterial secondary metabolites under simulated or spaceflight microgravity, the specific area of plant-beneficial compound production by bacteria remains largely unexplored in these contexts. In this study, the production of metabolites pyoluteorin, 2,4-diacetylphloroglucinol (DAPG), orfamide A produced by the plant-promoting bacterium Pseudomonas protegens Pf-5, and pyrroloquinoline quinone (PQQ) produced by Burkholderia ambifaria AMMD under simulated microgravity was analyzed. Transcriptomic analysis of the biosynthetic clusters, coupled with targeted metabolomics, revealed significant downregulation of ofaABC and pqqBCDE operons on Day 3 of incubation under simulated microgravity. This downregulation corresponded to reduced levels of orfamide A and pyrroloquinoline quinone, indicating a functional link between transcriptional suppression and decreased metabolite yield. Two complementary genetic engineering approaches were used to increase the production of these compounds: native chromosomal promoter replacement with either endogenous or inducible promoters, or plasmid-based operon overexpression. While the chromosomal strategy yielded modest expression improvements in P. protegens, the plasmid-based system enabled robust expression with a significant increase in pyrroloquinoline production in B. ambifaria. This study provides a first step for engineering these microbes to provide plant-promoting metabolites in microgravity as a mechanism of aiding the cultivation of plants aboard space-faring vehicles. IMPORTANCE: Bacteria play an essential role in supporting plant health by producing antifungal compounds that protect against fungal diseases. In space, these bacterial functions may be disrupted. This study examined how microgravity affects the production of such compounds in plant beneficial bacteria, Pseudomonas protegens and Bur

In beef cattle breeding and improvement, in vitro maturation (IVM) technology serves as the foundation of in vitro production (IVP) technology. However, oocytes inevitably suffer from aging damage during the IVM process, which severely impairs their quality and developmental potential, therefore developing in vitro culture strategies that can improve the quality of aged oocytes is crucial for enhancing the effectiveness of IVP. Pyrroloquinoline Quinone (PQQ) is a redox cofactor with multiple biological functions; it can exert cytoprotective effects by regulating processes such as oxidative stress, mitochondrial function, and autophagy, and its biological effects are often associated with the activation of the Nrf2 signaling pathway. This study aimed to clarify whether PQQ improved the quality and developmental potential of aged bovine oocytes by activating the Nrf2 pathway, and to investigate the effects of supplementing PQQ during IVM on relevant indicators of aged bovine oocytes. The results showed that supplementation with 10 μmol/L PQQ significantly increased the cleavage rate and blastocyst rate of aged bovine oocytes; simultaneously, it significantly downregulated the mRNA expression level of Keap1 and upregulated the mRNA expression levels of Nrf2, Akt, and their downstream target genes (SOD1, SOD2, HO-1, NQO1, and GCLC).The protein expression levels determined by Western blotting were consistent with the mRNA expression levels detected. In conclusion, PQQ activates the Nrf2 pathway to reduce reactive oxygen species (ROS) accumulation, enhance mitochondrial function, inhibit apoptosis, thereby improving aged bovine oocytes' quality and developmental potential, providing a theoretical and practical reference for optimizing bovine oocyte IVM systems.

BACKGROUND: Age-related knee osteoarthritis (OA) arises from cumulative oxidative damage, chondrocyte senescence and extracellular matrix loss; yet safe and effective disease‑modifying interventions for aging‑associated OA are lacking. Pyrroloquinoline quinone (PQQ; molecular formula C14H6N2O8) is a naturally bioactive compound that has been reported to activate nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that regulates antioxidant and cytoprotective gene expression. However, its effects on age-related OA and the underlying mechanisms remain unclear. METHODS: Twelve‑month‑old mice received dietary PQQ (4 mg/kg feed) for 12 months and joint pathology was assessed by Safranin O-Fast Green staining, osteoarthritis research society international (OARSI) grading, osteophyte and synovitis scoring, and micro‑computed tomography (μCT). Oxidative damage, senescence and extracellular matrix markers were analyzed. Human and mouse chondrocytes and cartilage explants were treated with interleukin-1β (IL‑1β) to model OA in vitro; effects of PQQ on oxidative stress, proliferation, senescence and matrix proteins were measured. Nrf2 signaling activation was examined. Mechanistic assays investigated how Nrf2 regulates the insulin‑like growth factor 1 receptor (IGF1R). Nrf2 or IGF1R loss‑of‑function evaluated pathway dependence. RESULTS: Long‑term dietary PQQ markedly reduced spontaneous, age‑related OA in mice. It lowered OARSI scores and reduced osteophyte formation and synovitis, while preserving cartilage and subchondral bone structure. PQQ also decreased oxidative DNA damage in cartilage, reduced senescence markers and senescence‑associated secretory phenotype (SASP) factors, and restored Lamin B1. In addition, it reduced matrix metalloproteinase‑13 (MMP13) and maintained COL2A1 expression. In IL‑1β‑challenged human chondrocytes and explants, PQQ suppressed oxidative stress, rescued proliferation, diminished senescence and prevented matrix degradation. PQQ enhanced Nrf2 nuclear accumulation, antioxidant response element (ARE) activity and antioxidant genes expression. Mechanistic assays identified IGF1R as a direct Nrf2 target; IGF1R knockdown b

Age-related macular degeneration (AMD) is a progressive retinal disorder characterised by oxidative stress and inflammation. Although pyrroloquinoline quinone (PQQ) has been reported to exert neuroprotective effects, its specific efficacy in in vivo models of AMD pathophysiology has not yet been elucidated. In this study, we evaluated the protective effects of PQQ against all-trans-retinal (ATR)-induced cytotoxicity in ARPE-19 cells and light-induced photoreceptor degeneration in rats. Pretreatment of ARPE-19 cells with PQQ dose-dependently mitigated ATR-induced cytotoxicity. In the in vivo model, rats received a single intraperitoneal injection of PQQ (2 or 5 mg/kg) 1 h prior to 1000-lux light exposure. Retinal function and morphology were evaluated by electroretinography and haematoxylin-eosin staining, respectively. The 5 mg/kg PQQ group retained significantly greater retinal function than the vehicle group at 3 days postexposure and demonstrated significant preservation of the outer nuclear layer at 7 days postexposure, indicating the suppression of photoreceptor cell death. Western blot analysis detected the dose-dependent suppression of light-induced c-Fos upregulation following PQQ treatment. These findings suggest that the protective effect of PQQ against phototoxic damage is associated with the suppression of c-Fos signalling, thus lending support to the further investigation of PQQ as a potential therapeutic agent for AMD.

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a ubiquitous organophosphate flame retardant posing potential threats to reproductive health. Given that TDCIPP toxicity is often linked to oxidative stress, pyrroloquinoline quinone (PQQ), a potent natural antioxidant and mitochondrial nutrient, was hypothesized to mitigate these adverse effects. This study investigated the impact of TDCIPP exposure on the in vitro maturation of mouse oocytes and evaluated the protective role of PQQ. Using an in vitro maturation model, we assessed the toxic effects of TDCIPP by examining the first polar body extrusion (PBE) rate and cumulus expansion, followed by analyses of oxidative stress (ROS and GSH), mitochondrial integrity (ATP content and distribution), and apoptosis-related markers through transcriptome sequencing (Smart RNA-seq), quantitative real-time PCR, and immunofluorescence. The results demonstrated that TDCIPP significantly suppressed cumulus expansion and reduced the PBE rate. Mechanistically, TDCIPP induced severe oxidative stress, disrupted mitochondrial function, and activated the apoptotic pathway. Furthermore, TDCIPP triggered early apoptotic signaling by downregulating Bcl-2 and upregulating Bax. Notably, supplementation with PQQ effectively reversed these detrimental effects by reducing intracellular ROS levels, maintaining GSH content, preserving mitochondrial density and ATP production, and inhibiting apoptosis. In conclusion, our findings provide new insights into the gamete toxicity of TDCIPP and suggest that PQQ may serve as a potential therapeutic agent to protect oocyte quality against environmental pollutant-induced damage.

Membrane-bound pyrroloquinoline quinone (PQQ)-dependent quinoproteins are key components of the periplasmic oxidative metabolism of acetic acid bacteria, yet several predicted enzymes remain experimentally uncharacterized. Here, we identified and characterized Pqq5 from Gluconobacter japonicus NBRC 3271 as a membrane-bound PQQ-dependent D-lactate dehydrogenase (mLDH). Overexpression of mLDH in a strain lacking six major membrane bound dehydrogenases markedly increased D-lactate dehydrogenase activity in membrane fractions. The enzyme showed a clear preference for D-lactate over L-lactate, exhibited maximal activity at pH 6.0, and retained substantial activity at pH 4.0-6.0. Kinetic analysis using membrane fractions yielded an apparent KM of 1.08 mM for D-lactate. Membrane fractions containing mLDH showed ubiquinone-1 reductase activity and D-lactate-dependent oxygen consumption, suggesting that the enzyme is involved in quinone-linked D-lactate oxidation. D-lactate dehydrogenase activity was decreased by EDTA treatment, and restored by supplementation with PQQ and CaCl2, supporting the assignment of mLDH as a quinoprotein. In addition, pyruvate was produced from D-lactate in an mLDH-dependent manner. In an engineered background lacking known D-lactate-oxidizing enzymes, overexpression of mLDH helped growth on D-lactate medium. Together, these results support the identification of Pqq5 as a membrane-bound PQQ-dependent D-lactate dehydrogenase in G. japonicus and suggest that this enzyme contributes to quinone-linked D-lactate utilization. KEY POINTS: • Pqq5 is a membrane-bound PQQ-dependent D-lactate dehydrogenase, mLDH • mLDH catalyzes D-lactate oxidation and ubiquinone reduction in membrane fractions • mLDH helps growth on D-lactate in an engineered G. japonicus background. © 2026. The Author(s).

Oxidative stress, driven by an imbalance between reactive oxygen species (ROS) production and antioxidant capacity (particularly glutathione, GSH), contributes significantly to the poor quality of in vitro maturation (IVM) oocytes. In this study, the role of the antioxidant pyrroloquinoline quinone (PQQ) during the IVM of porcine oocytes and its impact on subsequent embryonic development were investigated. Porcine cumulus oocyte complexes were cultured for 44 h in media supplemented with 0, 2.5, 5, or 10 μM PQQ. The results showed that 5 μM PQQ significantly increased the rates of cumulus expansion and nuclear maturation. Additionally, at this concentration, PQQ reduced ROS levels and Annexin V-FITC early apoptosis, upregulated the expression of antioxidant-related genes (SOD2, GPX and CAT), and modulated the expression of apoptosis-related genes (Bax and Bcl2). PQQ also increased ATP levels, mitochondrial membrane potential, and the mRNA expression of genes associated with mitochondrial biogenesis, including PGC-1α, NRF2, and TFAM. The supplementation of 5 μM PQQ during maturation resulted in significantly improved cleavage and blastocyst formation rates and total cell number of blastocysts after oocyte parthenogenetic activation. These results demonstrate that PQQ promotes porcine oocyte maturation and early embryonic development by reducing oxidative stress and enhancing mitochondrial function.

39. bioRxiv [Preprint]. 2026 Feb 13:2026.02.12.705540. doi: 10.64898/2026.02.12.705540. Thirty days of supplementation with PQQ reprograms immunometabolic networks in Western diet-fed female baboons. Dockins SG, Hyatt KE, Reuter DN, Stevens TL, Tresler AB, Papin JF, Myers DA, Jonscher KR. Western-style diets promote chronic metabolic inflammation and dyslipidemia, yet safe interventions that restore immunometabolic homeostasis remain limited. Pyrroloquinoline quinone (PQQ) is a naturally occurring redox cofactor with antioxidant and metabolic regulatory properties, but its systemic effects in translational preclinical models are poorly defined. Here, we examined the impact of short-term PQQ supplementation in obese adult female olive baboons ( Papio anubis ) chronically fed a Western diet. Using a human-equivalent dose administered for 30 days, we found that PQQ supplementation significantly reduced circulating markers of systemic inflammation and cholesterol in Western-diet-fed animals, lowering circulating C-reactive protein, soluble CD163, and atherogenic lipoprotein fractions independent of changes in adiposity. Proteomic and pathway analyses of circulating proteins in plasma and serum revealed suppression of complement, thrombo-inflammatory, and extracellular matrix remodeling pathways, alongside enhanced lipoprotein assembly, remodeling, and clearance. Network analyses identified restoration of neurotrophic tyrosine kinase receptor 1 (NTRK1)- and forkhead box A2 (FOXA2)-regulated signaling as central features of the PQQ response, accompanied by inhibition of pro-fibrotic, xenobiotic, and inflammatory pathways, as well as predicted activation of liver X receptor (LXR)- and insulin growth factor (IGF)-associated metabolic programs. These findings demonstrate that PQQ rapidly reprograms systemic immunometabolic networks in a nonhuman primate model of diet-induced metabolic stress, highlighting FOXA2- and neurotrophin-associated pathways as novel targets of PQQ's action.

Peak bone mass (PBM) critically determines lifelong skeletal health. We showed that dietary supplementation with pyrroloquinoline quinone (PQQ) - a water-soluble bioactive compound that activates nuclear factor erythroid 2-related factor 2 (Nrf2) signaling - during pregnancy or post-weaning enhances PBM acquisition in wild-type mice, subsequently attenuating age-related bone loss and improving mechanical strength. Mechanistically, PQQ-activated Nrf2 binds directly to the parathyroid hormone 1 receptor (Pth1r) promoter, upregulating its transcription and augmenting PTH-induced osteogenesis. Pth1r overexpression rescues the impaired osteogenesis of Nrf2-deficient bone marrow mesenchymal stem cells (BMSCs). Teriparatide's (PTH 1-34) anabolic effects are markedly compromised in Nrf2-deficient mice and human BMSCs, underscoring Nrf2's essential role in PTH-mediated bone formation. Notably, PQQ and PTH 1-34 co-administration synergistically enhances skeletal anabolism in aged mice beyond PTH 1-34 monotherapy. These results establish the PQQ-Nrf2-Pth1r axis as a key regulator of bone mass accrual and suggest PQQ as a promising adjunct to teriparatide for osteoporosis.

Interoception, the process by which the nervous system perceives and interprets internal bodily signals, is essential for athletes to effectively modulate motor decisions but may be impaired after exhaustive exercise. This study investigated the effects of pyrroloquinoline quinone (PQQ), nicotinamide mononucleotide (NMN), and their combination on interoception following acute exhaustive exercise. Sixty participants were randomly assigned in a double-blind, placebo-controlled trial to receive either placebo (320 mg cornflour), PQQ (20 mg PQQ + 300 mg cornflour), NMN (300 mg NMN + 20 mg cornflour), or a combined supplement (20 mg PQQ + 300 mg NMN). Supplements were ingested 60 min before completing an acute exhaustive exercise protocol using the Bruce treadmill test. Interoception was measured using the Body Perception Questionnaire (BPQ) and the Multidimensional Assessment of Interoceptive Awareness (MAIA) at baseline and post-exercise. Group differences were examined using chi-square and one-way ANOVA, while mixed-design ANOVA was applied to evaluate interoception and exercise capacity indicators. Significant improvements over time were observed in BPQ scores (89.45 vs. 95.08, p = 0.006), Self-regulation (2.79 vs. 3.02, p = 0.015), Body Listening (2.36 vs. 2.76, p < 0.001), and Trusting (2.97 vs. 3.21, p = 0.031). Body listening was the only domain that demonstrated a significant group × time interaction (p = 0.016), with the PQQ group showing significant improvement (p < 0.001). These findings suggest that PQQ supplementation may enhance specific aspects of interoception following acute exhaustive exercise.

Pyrroloquinoline quinone (PQQ) stimulates mitochondrial biogenesis and exhibits antioxidant properties. Since mitochondria play a crucial role in energy generation and metabolism, the present study aims to clarify whether PQQ is able to modulate energy expenditure and the development of obesity by regulating mitochondrial biogenesis. Male mice fed normal chow diet (NCD) or high fat diet (HFD) were supplemented with PQQ through drinking water for three months. Throughout this period, food and water intake, body weight, energy metabolic rate and the autonomous activity of the mice were measured. Then, the mice were sacrificed and the tissues were collected. Mitochondrial biogenesis, antioxidant capacity, and changes in gene expression were measured in liver tissue. The results showed that PQQ supplementation did not result in significant alterations in the food and water intake, body weight, and energy metabolic rate of the mice fed NCD or HFD although it significantly enhanced mitochondrial biogenesis and antioxidant capabilities of liver and promoted autonomous activity in NCD mice. Moreover, it had no impact on the adipose tissue mass in mice fed NCD or HFD. While PQQ supplementation induced the changes in metabolism-related genes such as CPT1a, SCD1, FABP1, HK2, HK3 and PGK1 in liver, it is suggested PQQ supplementation may influence lipid and glucose metabolism. However, PQQ-induced changes in hepatic gene expression and mitochondrial biogenesis are unable to alter systemic energy metabolism and adipose tissue accumulation in male mice. © 2025 The Authors.

OBJECTIVE: The present study evaluated the beneficial effects of pyrroloquinoline quinone (PQQ) on in vitro maturation (IVM) of porcine oocyte and subsequent early embryo development. METHODS: Porcine cumulus oocyte complexes were cultured in IVM medium with supplementation of 0, 200, 400, 800 or 1600 nM PQQ for 42 h. We first examined cumulus expansion index (CEI) and the rate of oocyte nuclear maturation. Then, we assessed oocyte mitochondrial function, oxidative stress levels, lipid metabolism and subsequent embryonic development. RESULTS: PQQ (800 nM) supplementation significantly increased CEI and the nuclear maturation rate of oocytes following IVM. Additionally, oocysts supplemented with 800 nM of PQQ showed significantly increased mitochondrial content, mitochondrial membrane potential, activity, and mRNA expression levels of genes associated with mitochondrial biogenesis (PGC-1a, NRF1, NRF2 and TFAM). PQQ significantly reduced the levels of reactive oxygen species, lipid drop-lets, and fatty acids content, while enhancing the mRNA expression levels of genes related to antioxidant activity (SOD1, SOD2, GPX and CAT), lipolysis (ATGL and HSL) and β-oxidation (CPT1B and CPT2) in porcine oocytes. PQQ (800 nM) supplementation significantly increased cleavage rate, blastocyst formation rate, and total blastocyst cell numbers following partheno-genetic activation. CONCLUSION: PQQ supplementation during IVM positively influences porcine oocyte maturation and subse-quent embryonic development by enhancing mitochondrial function and lipid metabolism and alleviating oxidative stress.

Aging is an inevitable biological process, driven in part by increased oxidative stress, which accelerates cellular damage and contributes to immune system dysfunction. Therefore, targeting oxidative stress has emerged as a potential strategy. Pyrroloquinoline quinone (PQQ), a potent antioxidant, has demonstrated significant efficacy in reducing oxidative stress and modulating immune responses, making it a promising therapeutic candidate. In this study, we investigated the effects of aging on the hematopoietic immune system (HIS) through single-cell RNA sequencing (scRNA-seq) of spleen and bone marrow cells in murine models. Our results revealed widespread age-related inflammation and oxidative stress within immune cell populations. Notably, long-term PQQ supplementation improved physiological parameters and reduced blood inflammatory factors levels in aged mice. Subsequent scRNA-seq analysis demonstrated that PQQ supplementation effectively reduced oxidative stress levels across various HIS cell types and reversed aging-related phenotypes, such as inflammatory responses and immunosenescence. Additionally, PQQ reversed aging-induced disrupted signaling and restored immune homeostasis, particularly in B cells and hematopoietic stem cells (HSCs). Importantly, we identified critical molecular targets, including ASPP1, which mediates PQQ's anti-apoptotic effects in B cells, and Yy1 and CD62L, which were upregulated by PQQ to restore HSCs self-renewal and differentiation potential. Furthermore, the machine learning program and experimental validation demonstrated the senolytic and senomorphic effects of PQQ in vivo and vitro. These findings underscore PQQ's potential not only in mitigating oxidative stress but also in restoring immune homeostasis and promoting cellular regeneration, highlighting its therapeutic potential in addressing immune aging and improving physiological function. © 2025 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.

Quinones are redox-active compounds with many beneficial biological functions and harmful effects. Owing to their high redox activity, quinones can be repetitively oxidized and reduced, producing reactive oxygen species, a process known as the quinone redox cycling. In the last two decades, the redox cycling of quinones has enabled several interesting analytical applications. These applications either use quinones as analytes or as probes for non-quinone analytes. In both cases, the redox cycling of quinone is compatible with various detection techniques, including colorimetry, chemiluminescence, fluorimetry, and electroanalytical methods. Despite the versatile and interesting applications of quinone redox cycling, no review has discussed their analytical capabilities. Therefore, we review the analytical applications of quinone redox cycling in this article, covering all detection strategies that have been applied where quinones were used as analytes or probes. In addition, attention was given to the analytical challenges and future prospects of quinone redox cycling.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by complex immune dysregulation, including abnormalities in macrophage polarization. Pyrroloquinoline quinone (PQQ) has been reported to exert anti-inflammatory and immunoregulatory effects in various disease models, but its role in SLE remains unclear. OBJECTIVE: To evaluate the therapeutic effects of PQQ in SLE and SLE-associated diffuse alveolar hemorrhage (DAH) and to assess its impact on macrophage activation. METHODS: Pristane-induced DAH mice and lupus-prone MRL/lpr mice were used to assess in vivo efficacy. Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) analyses were performed to characterize immune remodeling and explore underlying mechanisms. RAW264.7 macrophages were used to examine the inhibitory effects of PQQ on M1 macrophage polarization. RESULTS: PQQ alleviated lung injury in SLE-DAH mice and reduced splenomegaly, autoantibodies, renal inflammation, and systemic cytokines in MRL/lpr mice. Flow cytometry and scRNA-seq consistently demonstrated reductions in inflammatory macrophage populations. Bulk RNA-seq further indicated that PQQ modulated inflammatory pathways associated with macrophage activation. Moreover, PQQ significantly reduced the expression of inflammatory mediators (IL-6, TNF-α, and IL-1β), inhibited M1 macrophage polarization, and decreased the production of oxidative stress-associated indicators (ROS and NO) in LPS/IFN-γ-stimulated RAW264.7 cells. Finally, PQQ regulated ERK/MAPK signaling, which contributed to the attenuation of inflammatory responses. CONCLUSION: PQQ attenuates SLE and its pulmonary complication DAH by regulating macrophage polarization and may serve as a potential immunomodulatory therapeutic candidate.