Sativa
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Ray has mentioned Agmatine as having relevant therapeutic value - he mentions agmatine deficiency.
I've included various quotes from posts across the forum, as well as other research exploring Agmatine's metabolic interactions.
Here is some RP relevant insight into Agmatine's metabolic interactions.
Here is my original post which assembles lots of information on Agmatine, including insight from Travis on a potential agmatine-polyamine related issue (which can be partly mitigated by increasing methylglyoxal).
Agmatine apparently stimulates the endogenous synthesis of allopregnanolone via activation of the PPAR-α receptor & PGC1α! (paper attached)
Agmatine seems to have a protective effect on mitochondria and modulates fatty acid metabolism, oxygen consumption & ATP synthesis; also seems to prevent dysfunction of Complex I in renal cortex mitochondria, and indirectly regulates cytochrome c oxidase activity.
Agmatine diminished incomplete fatty acid oxidation, decreased fat but increased protein mass, increased hepatic ureagenesis & gluconeogesis but decreased glycolysis; stimulates β-oxidation.
—
Agmatine is transported into liver mitochondria by a specific electrophoretic mechanism
Agmatine transport in liver mitochondria may be of physiological importance as an indirect regulatory system of cytochrome c oxidase activity and as an inducer mechanism of mitochondrial-mediated apoptosis.
[Agmatine is transported into liver mitochondria by a specific electrophoretic mechanism]
—
The arginine metabolite agmatine protects mitochondrial function and confers resistance to cellular apoptosis
Agmatine, an endogenous metabolite of arginine, selectively suppresses growth in cells with high proliferative kinetics, such as transformed cells, through depletion of intracellular polyamine levels. In the present study, we depleted intracellular polyamine content with agmatine to determine if attrition by cell death contributes to the growth-suppressive effects. We did not observe an increase in necrosis, DNA fragmentation, or chromatin condensation in Ha-Ras-transformed NIH-3T3 cells administered agmatine. In response to Ca2+-induced oxidative stress in kidney mitochondrial preparations, agmatine demonstrated attributes of a free radical scavenger by protecting against the oxidation of sulfhydryl groups and decreasing hydrogen peroxide content. The functional outcome was a protective effect against Ca2+
[The arginine metabolite agmatine protects mitochondrial function and confers resistance to cellular apoptosis]
—
Agmatine effects on mitochondrial membrane potential and NF-κB activation protect against rotenone-induced cell damage in human neuronal-like SH-SY5Y cells.
Agmatine, an endogenous arginine metabolite, has been proposed as a novel neuromodulator that plays protective roles in the CNS in several models of cellular damage. However, the mechanisms involved in these protective effects in neurodegenerative diseases are poorly understood. The present study was undertaken to investigate the effects of agmatine on cell injury induced by rotenone, commonly used in establishing in vivo and in vitro models of Parkinson's disease, in human-derived dopaminergic neuroblastoma cell line (SH-SY5Y). We report that agmatine dose-dependently suppressed rotenone-induced cellular injury through a reduction of oxidative stress. Similar effects were obtained by spermine, suggesting a scavenging effect for these compounds. However, unlike spermine, agmatine also prevented rotenone-induced nuclear factor-κB nuclear translocation and mitochondrial membrane potential dissipation. Furthermore, rotenone-induced increase in apoptotic markers, such as caspase 3 activity, Bax expression and cytochrome c release, was significantly attenuated with agmatine treatment. These findings demonstrate mitochondrial preservation with agmatine in a rotenone model of apoptotic cell death, and that the neuroprotective action of agmatine appears because of suppressing apoptotic signalling mechanisms. Thus, agmatine may have therapeutic potential in the treatment of Parkinson's disease by protecting dopaminergic neuron
[Agmatine effects on mitochondrial membrane potential and NF-κB activation protect against rotenone-induced cell damage in human neuronal-like SH-SY... - PubMed - NCBI]
—
Different behavior of agmatine in liver mitochondria: Inducer of oxidative stress or scavenger of reactive oxygen species?
Agmatine acts as a competitive inhibitor of nitric oxide synthase (NOS) [4] and induces ornithine decarboxylase antizyme [5] and spermidine/spermine acetyl transferase [6]. In fact, in all species agmatine is metabolized by agmatinase to urea and putrescine [7], suggesting that it is a polyamine precursor. In mammals, agmatine is not only synthesized “in situ” by ADC but is also taken up by exogenous sources and transported to several organs, in particular the liver, by an energy-dependent mechanism [8]. It has been reported that, in rat hepatocytes, increased agmatine concentration, by provoking polyamine depletion, promotes apoptosis by increasing caspase-3 activity. This occurs through mitochondrial swelling and release of cytochrome c[9]. Agmatine has also been found in neuronal mitochondria[10], and its metabolic enzymes, ADC and agmatinase, have also been recognized in mitochondria [11], [12], [13], as well as the imidazoline receptor, I2, which binds agmatine although its function is still unknown [14]. Very recently it has also been found that agmatine is transported into liver mitochondria by an energy-dependent mechanism, exhibiting strict electrophoretic behavior and requiring high membrane potential (ΔΨ) in order to operate [15].
The transport of agmatine in RLM accounts for its up-regulation in ureagenesis, demonstrated in perfused liver [16], coupled with stimulation of β-oxidation [17]. Indeed, agmatine is also able to prevent dysfunction of Complex I in renal cortex mitochondria [18], most probably by phosphorylating the AQDQ subunit of the complex [19]. It has been proposed that these findings may have important implications for the prevention of mitochondrial diseases related to faulty Complex I [18].
All these observations, revealing close relationships between this amine and mitochondria, taken together with previous reports on interactions among biogenic amines and mitochondria, particularly at the level of oxygen consumption and ATP synthesis...
[Different behavior of agmatine in liver mitochondria: Inducer of oxidative stress or scavenger of reactive oxygen species? - ScienceDirect]
—
Anti-Atherosclerotic Action of Agmatine in ApoE-Knockout Mice
...Atherosclerosis is an inflammatory disease in which dysfunction of mitochondria play an important role, and disorders of lipid management intensify this process. Agmatine, an endogenous polyamine formed by decarboxylation of arginine, exerts a protective effect on mitochondria and modulates fatty acid metabolism.
[Anti-Atherosclerotic Action of Agmatine in ApoE-Knockout Mice]
—
The molecular and metabolic influence of long-term Agmatine consumption
Subsequently, AGM induced a widespread impact on gene expression and metabolic profiling, including: (a) activation of peroxisomal proliferator-activated receptor-α (PPARα), and its coactivator PGC1α; (b) increased expression of PPARγ and genes regulating thermogenesis, gluconeogenesis, and carnitine (Car) biosynthesis and transport. The changes in gene expression were coupled with improved tissue and systemic levels of Car and short chain AcylCar, increased βoxidation and diminished incomplete fatty acid oxidation, decreased fat but increased protein mass, increased hepatic ureagenesis and gluconeogesis but decreased glycolysis. These metabolic changes were coupled with reduced weight gain and a curtailment of the hormonal and metabolic derangements associated with HFD-induced obesity. The findings suggest that AGM elevated the synthesis and level of cAMP, thereby mimicking the effects of caloric restriction with respect to metabolic reprogramming.
[Attachment: https://raypeatforum.com/community/attachments/metabolic-influence-of-agmatine-pdf.14186/]
I've included various quotes from posts across the forum, as well as other research exploring Agmatine's metabolic interactions.
Here is some RP relevant insight into Agmatine's metabolic interactions.
Here is my original post which assembles lots of information on Agmatine, including insight from Travis on a potential agmatine-polyamine related issue (which can be partly mitigated by increasing methylglyoxal).
Agmatine apparently stimulates the endogenous synthesis of allopregnanolone via activation of the PPAR-α receptor & PGC1α! (paper attached)
Agmatine seems to have a protective effect on mitochondria and modulates fatty acid metabolism, oxygen consumption & ATP synthesis; also seems to prevent dysfunction of Complex I in renal cortex mitochondria, and indirectly regulates cytochrome c oxidase activity.
Agmatine diminished incomplete fatty acid oxidation, decreased fat but increased protein mass, increased hepatic ureagenesis & gluconeogesis but decreased glycolysis; stimulates β-oxidation.
—
Agmatine is transported into liver mitochondria by a specific electrophoretic mechanism
Agmatine transport in liver mitochondria may be of physiological importance as an indirect regulatory system of cytochrome c oxidase activity and as an inducer mechanism of mitochondrial-mediated apoptosis.
[Agmatine is transported into liver mitochondria by a specific electrophoretic mechanism]
—
The arginine metabolite agmatine protects mitochondrial function and confers resistance to cellular apoptosis
Agmatine, an endogenous metabolite of arginine, selectively suppresses growth in cells with high proliferative kinetics, such as transformed cells, through depletion of intracellular polyamine levels. In the present study, we depleted intracellular polyamine content with agmatine to determine if attrition by cell death contributes to the growth-suppressive effects. We did not observe an increase in necrosis, DNA fragmentation, or chromatin condensation in Ha-Ras-transformed NIH-3T3 cells administered agmatine. In response to Ca2+-induced oxidative stress in kidney mitochondrial preparations, agmatine demonstrated attributes of a free radical scavenger by protecting against the oxidation of sulfhydryl groups and decreasing hydrogen peroxide content. The functional outcome was a protective effect against Ca2+
[The arginine metabolite agmatine protects mitochondrial function and confers resistance to cellular apoptosis]
—
Agmatine effects on mitochondrial membrane potential and NF-κB activation protect against rotenone-induced cell damage in human neuronal-like SH-SY5Y cells.
Agmatine, an endogenous arginine metabolite, has been proposed as a novel neuromodulator that plays protective roles in the CNS in several models of cellular damage. However, the mechanisms involved in these protective effects in neurodegenerative diseases are poorly understood. The present study was undertaken to investigate the effects of agmatine on cell injury induced by rotenone, commonly used in establishing in vivo and in vitro models of Parkinson's disease, in human-derived dopaminergic neuroblastoma cell line (SH-SY5Y). We report that agmatine dose-dependently suppressed rotenone-induced cellular injury through a reduction of oxidative stress. Similar effects were obtained by spermine, suggesting a scavenging effect for these compounds. However, unlike spermine, agmatine also prevented rotenone-induced nuclear factor-κB nuclear translocation and mitochondrial membrane potential dissipation. Furthermore, rotenone-induced increase in apoptotic markers, such as caspase 3 activity, Bax expression and cytochrome c release, was significantly attenuated with agmatine treatment. These findings demonstrate mitochondrial preservation with agmatine in a rotenone model of apoptotic cell death, and that the neuroprotective action of agmatine appears because of suppressing apoptotic signalling mechanisms. Thus, agmatine may have therapeutic potential in the treatment of Parkinson's disease by protecting dopaminergic neuron
[Agmatine effects on mitochondrial membrane potential and NF-κB activation protect against rotenone-induced cell damage in human neuronal-like SH-SY... - PubMed - NCBI]
—
Different behavior of agmatine in liver mitochondria: Inducer of oxidative stress or scavenger of reactive oxygen species?
Agmatine acts as a competitive inhibitor of nitric oxide synthase (NOS) [4] and induces ornithine decarboxylase antizyme [5] and spermidine/spermine acetyl transferase [6]. In fact, in all species agmatine is metabolized by agmatinase to urea and putrescine [7], suggesting that it is a polyamine precursor. In mammals, agmatine is not only synthesized “in situ” by ADC but is also taken up by exogenous sources and transported to several organs, in particular the liver, by an energy-dependent mechanism [8]. It has been reported that, in rat hepatocytes, increased agmatine concentration, by provoking polyamine depletion, promotes apoptosis by increasing caspase-3 activity. This occurs through mitochondrial swelling and release of cytochrome c[9]. Agmatine has also been found in neuronal mitochondria[10], and its metabolic enzymes, ADC and agmatinase, have also been recognized in mitochondria [11], [12], [13], as well as the imidazoline receptor, I2, which binds agmatine although its function is still unknown [14]. Very recently it has also been found that agmatine is transported into liver mitochondria by an energy-dependent mechanism, exhibiting strict electrophoretic behavior and requiring high membrane potential (ΔΨ) in order to operate [15].
The transport of agmatine in RLM accounts for its up-regulation in ureagenesis, demonstrated in perfused liver [16], coupled with stimulation of β-oxidation [17]. Indeed, agmatine is also able to prevent dysfunction of Complex I in renal cortex mitochondria [18], most probably by phosphorylating the AQDQ subunit of the complex [19]. It has been proposed that these findings may have important implications for the prevention of mitochondrial diseases related to faulty Complex I [18].
All these observations, revealing close relationships between this amine and mitochondria, taken together with previous reports on interactions among biogenic amines and mitochondria, particularly at the level of oxygen consumption and ATP synthesis...
[Different behavior of agmatine in liver mitochondria: Inducer of oxidative stress or scavenger of reactive oxygen species? - ScienceDirect]
—
Anti-Atherosclerotic Action of Agmatine in ApoE-Knockout Mice
...Atherosclerosis is an inflammatory disease in which dysfunction of mitochondria play an important role, and disorders of lipid management intensify this process. Agmatine, an endogenous polyamine formed by decarboxylation of arginine, exerts a protective effect on mitochondria and modulates fatty acid metabolism.
[Anti-Atherosclerotic Action of Agmatine in ApoE-Knockout Mice]
—
The molecular and metabolic influence of long-term Agmatine consumption
Subsequently, AGM induced a widespread impact on gene expression and metabolic profiling, including: (a) activation of peroxisomal proliferator-activated receptor-α (PPARα), and its coactivator PGC1α; (b) increased expression of PPARγ and genes regulating thermogenesis, gluconeogenesis, and carnitine (Car) biosynthesis and transport. The changes in gene expression were coupled with improved tissue and systemic levels of Car and short chain AcylCar, increased βoxidation and diminished incomplete fatty acid oxidation, decreased fat but increased protein mass, increased hepatic ureagenesis and gluconeogesis but decreased glycolysis. These metabolic changes were coupled with reduced weight gain and a curtailment of the hormonal and metabolic derangements associated with HFD-induced obesity. The findings suggest that AGM elevated the synthesis and level of cAMP, thereby mimicking the effects of caloric restriction with respect to metabolic reprogramming.
[Attachment: https://raypeatforum.com/community/attachments/metabolic-influence-of-agmatine-pdf.14186/]
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