Infos über PQQ (pyrroloquinoline quinone)

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Infos über PQQ (pyrroloquinoline quinone)

#2467

Beitragvon FluorchiNO » 02.11.2017, 08:40

PQQ (pyrroloquinoline quinone)

In diesem Artikel (schwere Kost, aber lesenswert!)

Treatment of the Fluoroquinolone-Associated Disability: The Pathobiochemical Implications
Krzysztof Michalak,1,2 Aleksandra Sobolewska-Włodarczyk,3 Marcin Włodarczyk,3 Justyna Sobolewska,4 Piotr Woźniak,4 and Bogusław Sobolewski4
https://www.hindawi.com/journals/omcl/2017/8023935/

erwähnen die Autoren PQQ als potentielle Behandlungsmöglichkeit des FC induzierten Syndroms:

Supporting the mitochondrial replication in the cell—pulling more damage to apoptosis and proliferation of the more healthy ones: supporting the mitochondrial exchange (removing that destroyed ones and replication of that more healthy ones) is the necessary way in the case of irreversible mtDNA damage. The substance that is postulated to possess the ability to promote the mitochondrial biogenesis is pyrroloquinoline quinone (PQQ) [107, 108]. This substance is also postulated to be OS protective


PQQ kann in der Tat die mitochondriale Biogenesis fördern.

Artikel von Dr.Michalzik:

http://www.dr-michalzik.de/blog/pqq/

Pyrroloquinoline Quinone Stimulates Mitochondrial Biogenesis through cAMP Response Element-binding Protein Phosphorylation and Increased PGC-1α Expression*
Winyoo Chowanadisai‡, Kathryn A. Bauerly‡, Eskouhie Tchaparian§, Alice Wong¶, Gino A. Cortopassi‖ and Robert B. Rucker‡,
http://www.jbc.org/content/285/1/142.short

Bioactive compounds reported to stimulate mitochondrial biogenesis are linked to many health benefits such increased longevity, improved energy utilization, and protection from reactive oxygen species.

Previously studies have shown that mice and rats fed diets lacking in pyrroloquinoline quinone (PQQ) have reduced mitochondrial content. Therefore, we hypothesized that PQQ can induce mitochondrial biogenesis in mouse hepatocytes.
(...)
The ability of PQQ to stimulate mitochondrial biogenesis accounts in part for action of this compound and suggests that PQQ may be beneficial in diseases associated with mitochondrial dysfunction


Pyrroloquinoline Quinone Modulates Mitochondrial Quantity and Function in Mice
1Tracy Stites*, David Storms*, Kathryn Bauerly*, James Mah**, Calliandra Harris*, Andrea Fascetti†, Quinton Rogers†, Eskouhie Tchaparian*, Michael Satre*, and Robert B. Rucker*,2
http://jn.nutrition.org/content/136/2/390.short

When pyrroloquinoline quinone (PQQ) is added to an amino acid-based, but otherwise nutritionally complete basal diet, it improves growth-related variables in young mice. We examined PQQ and mitochondrial function based on observations that PQQ deficiency results in elevated plasma glucose concentrations in young mice, and PQQ addition stimulates mitochondrial complex 1 activity in vitro. PQQ-deficient weanling mice had a 20–30% reduction in the relative amount of mitochondria in liver; lower respiratory control ratios, and lower respiratory quotients than PQQ-supplemented mice (2 mg PQQ/kg diet). In mice from dams fed a conventional laboratory diet, but switched at weaning to the basal diet, plasma glucose, Ala, Gly, and Ser concentrations were elevated at 4 wk (PQQ− vs. PQQ+), but not at 8 wk. The relative mitochondrial content (ratio of mtDNA to nuclear DNA) also tended (P < 0.18) to be lower (PQQ− vs. PQQ+) at 4 wk, but not at 8 wk. PQQ also counters the mitochondrial complex 1 inhibitor, diphenylene iodonium (DPI). Mice were gavaged with 0, 0.4, or 4 μg PQQ/g body weight (BW) daily for 14 d. At each PQQ level, DPI was injected (i.p.) at 0, 0.4, 0.8, or 1.6 μg DPI/g BW. The PQQ-deficient mice exposed to 0.4 or 4.0 μg DPI/g lost weight and had lower plasma glucose levels than PQQ-supplemented mice (P < 0.05). In addition, fibroblasts took up 3H-PQQ added to cell cultures, and cultured hepatocytes maintained mitochondrial PQQ concentrations similar to those observed in vivo. Collectively, these results indicate that dietary PQQ can influence mitochondrial amount and function, particularly in perinatal and weanling mice


Exp Ther Med. 2015 August; 10(2): 451–458.
Biological effects of pyrroloquinoline quinone on liver damage in Bmi-1 knockout mice
YUANQING HUANG,1,2 NING CHEN,1 and DENGSHUN MIAO1
http://europepmc.org/articles/PMC4509087

Pyrroloquinoline quinone (PQQ) has been demonstrated to function as an antioxidant by scavenging free radicals and subsequently protecting the mitochondria from oxidative stress-induced damage.

The aim of the present study was to investigate whether PQQ is able to rescue premature senescence in the liver, induced by the deletion of B cell-specific Moloney MLV insertion site-1 (Bmi-1), by inhibiting oxidative stress. In vivo, the mice were allocated into three groups that underwent the following treatment protocols. WT mice received a normal diet, while BKO mice also received a normal diet. An additional group of BKO mice were fed a PQQ-supplemented diet (BKO + PQQ; 4 mg PQQ/kg in the normal diet). The results indicated that PQQ partially rescued the liver damage induced by the deletion of Bmi-1. PQQ was demonstrated to exhibit these therapeutic effects on liver damage through multiple aspects, including the promotion of proliferation, antiapoptotic effects, the inhibition of senescence, the upregulation of antioxidant ability, the downregulation of cell cycle protein expression, the scavenging of reactive oxygen species and the reduction of DNA damage. The results of these experiments indicated that treatment of BKO mice with a moderate dose of PQQ significantly protected the liver from deleterious effects by inhibiting oxidative stress and participating in DNA damage repair. Therefore, PQQ has great potential as a therapeutic agent against oxidative stress during liver damage.


Seite des japanischen Herstellers Mitshubishi Gas Chemical von BioPQQ:

http://www.biopqq.com/

Offensichtlich wurde dieser BioPQQ in wissenschaftlichen Studien mehrfach verwendet.

Pyrroloquinoline quinone was discovered as the third coenzyme for oxidoreductases next to nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD) in 1979. In 2003, Researchers of Riken reported the possibility that Pyrroloquinoline quinone is the 14th vitamin in mammals. Pyrroloquinoline quinone has potent anti-oxidative and nerve protective activities. We have established our original manufacturing technology of Pyrroloquinoline quinone by fermentation of bacteria, and put it on the market as a research reagent.

Recently, it was found that Pyrroloquinoline quinone improved memory and learning capacity in rats.
Pyrroloquinoline quinone has great potential as a safe ingredient of dietary supplement for the brain.

Physiological Activity
Anti-oxidative activity
Protection of neurons
Regeneration of neurons
Promotion of synthesis of nerve growth factor (NGF)
Improvement of memory and learning capacity


aus: http://www.mgc.co.jp/eng/products/nop/10.html

Safety
NOAEL > 100mg/kg/day (rat, 90-day, oral)
Core batteries of genotoxicity study: Negative
Human clinical study (20 and 60mg/day): No toxicity
Functions:
Neuroprotective activity
Anti-oxidative activity
Mitochondrial biogenesis


aus http://www.biopqq.com/heritage/

Wissenschaftliche Studien mit PQQ:

http://www.biopqq.com/references/



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Re: Infos über PQQ (pyrroloquinoline quinone)

#2468

Beitragvon FluorchiNO » 02.11.2017, 09:01

Sicherheit (Safety) von PQQ

Regul Toxicol Pharmacol. 2013 Nov;67(2):189-97. doi: 10.1016/j.yrtph.2013.07.007. Epub 2013 Jul 25.
Genotoxicity of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™).
Nakano M1, Suzuki H, Imamura T, Lau A, Lynch B.
Author information
1Niigata Research Laboratory, Mitsubishi Gas Chemical Co., Inc., 182 Tayuhama, Shinwari, Kita-ku, Niigata 950-3112, Japan.
https://www.ncbi.nlm.nih.gov/pubmed/23891671

Abstract
The genotoxic potential of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™) was evaluated in a battery of genotoxicity tests. The results of the bacterial mutation assay (Ames test) were negative. Weak positive results were obtained in 2 separate in vitro chromosomal aberration test in Chinese hamster lung (CHL) fibroblasts. Upon testing in an in vitro chromosomal aberration test in human peripheral blood lymphocytes, no genotoxic activity of PQQ was noted. In the in vivo micronucleus assay in mice, PQQ at doses up to 2,000 mg/kg body weight demonstrated that no genotoxic effects are expressed in vivo in bone marrow erythrocytes. The weak responses in the in vitro test CHL cells were considered of little relevance under conditions of likely human exposure. PQQ disodium was concluded to have no genotoxic activity in vivo.


Copyright © 2013 Elsevier Inc. All rights reserved.

Regul Toxicol Pharmacol. 2014 Oct;70(1):107-21. doi: 10.1016/j.yrtph.2014.06.024. Epub 2014 Jul 1.
Acute and subchronic toxicity studies of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™) in rats.
Nakano M1, Takahashi H2, Koura S2, Chung C3, Tafazoli S4, Roberts A3.
Author information
1 NC Planning & Development Division, Mitsubishi Gas Chemical Co., Inc., 5-2, Marunouchi 2-chome, Chiyoda-ku, Tokyo, Japan.
2 Central Laboratories, New Drug Research Center, Inc., 452-1, Toiso, Eniwa-shi, Hokkaido, Japan.
3 Intertek Scientific & Regulatory Consultancy, 2233 Argentia Rd., Suite 308, Mississauga, Ontario L5N 2X7, Canada.
4 Intertek Scientific & Regulatory Consultancy, 2233 Argentia Rd., Suite 308, Mississauga, Ontario L5N 2X7, Canada. Electronic address: shahrzad.tafazoli@intertek.com.
https://www.sciencedirect.com/science/a ... 0014001482

Abstract
The potential use of pyrroloquinoline quinone disodium salt (BioPQQ™), as a supplemental food ingredient, was evaluated in a range of oral toxicity studies in rats including an acute study, a 14-day preliminary and a 28-day repeated-dose study, and a 13-week subchronic study. The median lethal dose of BioPQQ™ was shown to be 1000-2000mg/kg body weight (bw) in male and 500-1000mg/kgbw in female rats. In the 14-day study, high doses of BioPQQ™ resulted in increases in relative kidney weights with associated histopathology in female rats only, while a follow-up 28-day study in female animals resulted in increases in urinary protein and crystals. These findings were reversible, and resolved during the recovery period. In the 13-week study, a number of clinical chemistry findings and histopathological changes were noted, which were deemed to be of no toxicological significance, as the levels were within the historical control range, were not dose-dependent, occurred at a similar frequency in control groups, or only occurred in the control group. Based on these findings, a no-observed-adverse-effect level of 100mg/kgbw/day was determined for BioPQQ™ in rats, the highest dose tested in the 13-week study.


Copyright © 2014 Elsevier Inc. All rights reserved.

Merke: in klinischen Humanstudien wurden 10 bis 20 mg BioPQQ pro Tag verabreicht.

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Re: Infos über PQQ (pyrroloquinoline quinone)

#2469

Beitragvon FluorchiNO » 02.11.2017, 09:08

Klinische Humanstudien mit PQQ bzw BioPQQ™

In den folgenden Studien wurden den Probanden 20 mg BioPQQ pro Tag verabreicht.

Adv Exp Med Biol. 2016;876:319-25. doi: 10.1007/978-1-4939-3023-4_40.
Effect of the Antioxidant Supplement Pyrroloquinoline Quinone Disodium Salt (BioPQQ™) on Cognitive Functions.
Itoh Y1, Hine K1, Miura H1, Uetake T2, Nakano M3, Takemura N4, Sakatani K4,5.
https://www.ncbi.nlm.nih.gov/pubmed/26782228

Abstract
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.


Die 41 älteren Probanden haben 12 Wochen lang 20 mg BioPQQ eingenommen. Damit stieg die Durchblutung des Gehirns im präfrontalen Cortex (was übrigens bei Patienten mit ADHS von hohem Interesse ist) und ihre Aufmerksamkeit und Arbeitsgedächtnis besserten sich.

Diese guten Ergebnisse konnten in einer weiteren klinischen Studie bestätigt werden:
https://www.ncbi.nlm.nih.gov/pubmed/27526146

The Journal of Nutritional Biochemistry
Volume 24, Issue 12, December 2013, Pages 2076-2084
Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects
Calliandra B.HarrisaWinyooChowanadisaiaDarya O.MishchukaMike A.SatreaCarolyn M.SlupskyabRobert B.Ruckera
http://www.sciencedirect.com/science/ar ... ia%3Dihub#!

Abstract
Pyrroloquinoline quinone (PQQ) influences energy-related metabolism and neurologic functions in animals. The mechanism of action involves interactions with cell signaling pathways and mitochondrial function. However, little is known about the response to PQQ in humans. Using a crossover study design, 10 subjects (5 females, 5 males) ingested PQQ added to a fruit-flavored drink in two separate studies. In study 1, PQQ was given in a single dose (0.2 mg PQQ/kg). Multiple measurements of plasma and urine PQQ levels and changes in antioxidant potential [based on total peroxyl radical-trapping potential and thiobarbituric acid reactive product (TBAR) assays] were made throughout the period of 48 h. In study 2, PQQ was administered as a daily dose (0.3 mg PQQ/kg). After 76 h, measurements included indices of inflammation [plasma C-reactive protein, interleukin (IL)-6 levels], standard clinical indices (e.g., cholesterol, glucose, high-density lipoprotein, low-density lipoprotein, triglycerides, etc.) and 1H-nuclear magnetic resonance estimates of urinary metabolites related in part to oxidative metabolism. The standard clinical indices were normal and not altered by PQQ supplementation. However, dietary PQQ exposure (Study 1) resulted in apparent changes in antioxidant potential based on malonaldehyde-related TBAR assessments. In Study 2, PQQ supplementation resulted in significant decreases in the levels of plasma C-reactive protein, IL-6 and urinary methylated amines such as trimethylamine N-oxide, and changes in urinary metabolites consistent with enhanced mitochondria-related functions. The data are among the first to link systemic effects of PQQ in animals to corresponding effects in humans.


In dieser Studie mit 10 Probanden wurde in der Studie 1 0,2 mg PQQ/KG Körpergewicht einmalig verabreicht, in der Studie 2 0,3 mg PQQ/KG Körpergewicht täglich (wie lang?). Nach 76 Stunden waren die klinischen Indizien normal. Die einmalige 0,2 mg Dosis führte zu Veränderungen im antioxidativen Potential. Die tägliche 0,3 mg Dosis führte zu einer signifikanten Reduzierung der Serumspiegel von CRP, IL 6 und methylierten Aminosäuren (?) wie trimethylamine N-oxide und Veränderung in Metaboliten des Urins, die mit eine erhöhten mitochondrialen Funktionen übereinstimmend sind.

Journal of Nutritional Science and Vitaminology
Vol. 61 (2015) No. 3 p. 233-240
Effects of Pyrroloquinoline Quinone Disodium Salt Intake on the Serum Cholesterol Levels of Healthy Japanese Adults
Masahiko NAKANO1), Yuuki KAWASAKI2), Naoko SUZUKI2), Tsuyoshi TAKARA3)
1) Planning and Development Division, Natural Gas Chemicals Company, Mitsubishi Gas Chemical Company, Inc.
2) Research and Development Department, Orthomedico Inc. 3) Seishin-kai Medical Association Inc., Takara Medical Clinic
https://www.jstage.jst.go.jp/article/jn ... 3/_article

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 (BioPQQTM) 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


Bei Raten konnten die orale Einnahme von PQQ die Triglyzeride-Serumspiegel senken.
In dieser Studie bei Menschen (40-57 Jahr alt), die 12 Wochen lang 20 mg BioPQQ/Tag einnahmen, konnte der TG Spiegel nicht gesenkt werden, dennoch konnte der LDL Serumspiegel leicht gesenkt werden und sogar bei Patienten mit den zuvor höheren LDL Spiegeln signifikant gesenkt werden. Hohe LDL Spiegel seien Risikofaktoren für verschiedenen "lifestyle" Erkrankungen (Erkrankungen, die durch den Lebensmittel, also Ernährung, Bewegung, usw. beeinflusst werden).


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