Alpha-synuclein-induced mitochondrial dys... - Cure Parkinson's

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Alpha-synuclein-induced mitochondrial dysfunction is mediated via a sirtuin 3-dependent pathway 2020 (Honokiol)

Bolt_Upright profile image
17 Replies

More positive info on Honokiol: Alpha-synuclein-induced mitochondrial dysfunction is mediated via a sirtuin 3-dependent pathway ncbi.nlm.nih.gov/pmc/articl...

So this paper is all about activating Sirt 3 to decrease alpha synuclean:

"Together, our findings suggest that pharmacologically increasing SIRT3 levels can counteract αsyn-induced mitochondrial dysfunction by reducing αsyn oligomers and normalizing mitochondrial bioenergetics. These data support a protective role for SIRT3 in PD-associated pathways and contribute significant mechanistic insight into the interplay of SIRT3 and αsyn."

AND THIS paper is about how Honokiol activates Sirt 3: SIRT3 activator Honokiol attenuates β-Amyloid by modulating amyloidogenic pathway 2018 ncbi.nlm.nih.gov/pmc/articl...

"In this study, we report that Honokiol, an activator of SIRT3 attenuated oxidative stress and beta amyloid secretion in PS70 cells, in addition to improving mitochondrial function. High dose insulin treatment caused increased ROS levels, decrease in mitochondrial functions and increased formation of beta amyloid. Honokiol counteracted these effects by activating SIRT3 and by increasing in AMPK, CREB and PGC1α protein levels thereby causing reduction in beta-secretase activity. Compelling evidence has shown that Honokiol, a SIRT3 activator, expresses many beneficial effects in neurodegenerative diseases [65]. However, there are very few studies that have elucidated the novel mechanisms of SIRT3-mediated decrease in Aβ production. To the best of our knowledge this is the first report describing an activator of SIRT3 capable of improving mitochondrial function, and blocking the beta secretase activity thereby decreasing beta amyloid secretion."

I started Honokiol on advice for my REM Sleep Behavior Disorder, but the more I researched the better it looked. I take 200 mg of Swanson Magnolia Extract that is 90% Honokiol and Magnolol at night, and also take Palmitoylethanolamide at night that also has 180 mg of Honokiol. So I should be getting between 180 and 380 mg of Honokiol. Probably closer to 180 mg as I don't know how much of the Swanson is Magnolol.

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Bolt_Upright profile image
Bolt_Upright

I don't mind that part of my Magnolia Extract is Magnolol as Magnolol shows up in good reports also: Magnolol attenuates the locomotor impairment, cognitive deficit, and neuroinflammation in Alzheimer’s disease mice with brain insulin resistance via up-regulating miR-200c 2021 tandfonline.com/doi/full/10...

"In conclusion, our research demonstrated that Magnolol can alleviate the cognitive impairment, neuroinflammation and other symptoms of AD mice by up-regulating the expression of miR-200c."

Despe profile image
Despe in reply to Bolt_Upright

amazon.com/Magnolia-Bark-Ex...

This is what I purchased. First bottle I bought was $99! amazon.com/EcoNugenics-Hono...

Bolt_Upright profile image
Bolt_Upright in reply to Despe

120 capsules per container at 250 mg per capsule actually sounds okay. My Swanson brand is cheap, but it is 90% Magnolol and Honokiol. No idea how much of each. But I get 200 mg of Honokiol with my PM PEA tablet also.

Ghmac profile image
Ghmac in reply to Bolt_Upright

So Bolt has this helped your REM sleep disorder?

Bolt_Upright profile image
Bolt_Upright in reply to Ghmac

It is hard to say. I thought I was getting past the RBD but last night I was chased by alligators.

MarionP profile image
MarionP in reply to Bolt_Upright

You people are so full of it. Just get a very low dose of clonazepam and let it go at that, it will take care of your REM sleep disorder without any trouble.

in reply to MarionP

I would rather be full of “it” than Clonazepam. It has been shown to increase risk of dementia.

You have recommended it before and never respond to the info presented stating it increases dementia risk.

If I am wrong , please show me reputable info. I won’t hold my breath.

Clonazepam
in reply to Despe

Despe, I was looking at the brand you bought and others. Do you know if your brand is third party tested? I have not seen indication of that but I can’t find one that is.

Despe profile image
Despe in reply to

I didn't see that, but they test their own supplements. Did you read the description, sources, etc.?

Milk thistle?

“Age-related disease usually occurs with high frequency after a certain point, and these diseases are always accompanied by the gradual decline of function in various organs. In this section, we mainly focus on aging, Alzheimer's disease (AD) 47, Parkinson's disease (PD) 48, Huntington's disease (HD) 49, amyotrophic lateral sclerosis (ALS) 50 and age-related hearing loss (Figure ​(Figure3).3). Aging is a complex and irreversible process. Although the pathological features of aging vary considerably, they all bear the common characteristic that the smallest components of lesions, such as neuronal or muscle cells, have decreased or imbalanced mitochondrial function and increased oxidative damage 51. Under normal circumstances, SIRT3 is highly expressed in the brain and nervous system, but decreased SIRT3 expression is always observed in age-related diseases and this age-dependent defect of SIRT3 is a major risk factor of pathogenesis 52-54.”

ncbi.nlm.nih.gov/pmc/articl...

I believe Milk thistle aka silymarin is a Sirt 3 activator too.

I wonder if taking that as well would be too much. I take it for liver health. Concerned about my liver meds and supplements.

Bolt_Upright profile image
Bolt_Upright in reply to

Activation of Sirtuin 3 by Silybin Attenuates Mitochondrial Dysfunction in Cisplatin-induced Acute Kidney Injury 2017 frontiersin.org/articles/10...

Bolt_Upright profile image
Bolt_Upright in reply to

Adding the title of that document link: Mitochondrial Sirtuin 3: New emerging biological function and therapeutic target 2020 ncbi.nlm.nih.gov/pmc/articl...

"Positive modulators of SIRT3

SIRT3 dysfunction is closely related to the occurrence and development of various diseases, and activation of SIRT3 appears to be an effective strategy for the treatment of many diseases. Unfortunately, to date SIRT3 agonist has ever been reported to date. Several positive modulators of SIRT3 were reported, which can stimulate SIRT3 by elevating SIRT3 expression. By upregulating SIRT3, they have displayed promising therapeutic effects in some diseases such as cardiac hypertrophy, acute kidney injury, and others (Table ​(Table3).3). Of note, most positive regulators of SIRT3 are derived from natural products. For instance, Honokiol is one of the most studied SIRT3 activators and is a natural lignan derived from the bark of Magnolia. Honokiol could increase SIRT3 expression and deacetylation activity, which have a favorable effect on heart disease 16, 137, renal disease 173, surgery/anesthesia-induced cognitive decline 174 and Vitiligo 175. For heart disease, Honokiol activation of SIRT3 further decreases the acetylation levels of MnSOD2 and OSCP, resulting in improved mitochondrial rate of oxygen consumption and inhibition of ROS synthesis. In addition, Honokiol suppresses cardiac hypertrophy and fibrosis via SIRT3-regulated AKT and ERK1/2 inhibition in mice with cardiac hypertrophy 16. Furthermore, in mice with doxorubicin-induced cardiomyopathy, Honokiol activated SIRT3 to promote mitochondrial fusion and inhibit apoptosis. More intriguingly, activation of SIRT3 by Honokiol can protect against doxorubicin-induced cardiotoxicity in tumor-xenograft mice without affecting the anti-tumor effect of doxorubicin. This makes it possible for Honokiol to contribute to adjuvant therapy of chemotherapy 137. In renal disease, Honokiol stimulates SIRT3 activity to block the NF-κB-TGF- β1/Smad regulated inflammation and fibrosis signaling in renal fibrosis mice model 173. Surprisingly, Honokiol can ameliorate surgery-induced or anesthesia-induced cognitive decline in mice via SIRT3 activation mediating ROS elimination and apoptosis inhibition 174. Interestingly, honokiol could improve vitiligo via melanocyte apoptosis inhibition through SIRT3-OPA1 axis activation 175. These studies suggest that Honokiol may be helpful in the treatment of various diseases, whether used alone or as an adjunct therapy. Silybin is another natural plant-derived SIRT3 activator. It is isolated from the seeds of blessed milkthistle (Silybum marianum) and is used as a hepatoprotectant in traditional Chinese medicine. It was reported that Silybin can improve kidney mitochondrial function via activating SIRT3 in a mouse model of cisplatin-induced acute kidney injury. Up-regulation of SIRT3 eliminates ROS and inhibits apoptosis to protect kidney cells from death. It is noteworthy that this protective effect can decrease cisplatin-induced renal toxicity and may contribute to clinical adjuvant treatment in cisplatin chemotherapy 176. Resveratrol, a famous SIRT1 activator (although resveratrol-mediated activation of sirtuins has been repeatedly shown to be an experimental artifact, it does have biological activity in vivo), can also increase the expression of SIRT3 to attenuate acute kidney injury 177. Fascinatingly, Dihydromyricetin has a similar chemical structure to Resveratrol and it can elevate the expression of SIRT3 through SIRT3 mediated cytoprotection and inflammatory resistance, thus treating osteoarthritis 172. Polydatin, a polyphenolic compound isolated from Polygonum cuspidatum, can initiate SIRT3-regulated mitochondrial autophagy to protect cardiomyocytes from myocardial infarction 178. Moreover, in a mouse model of sulfur mustard-induced hepatic injury, this natural product exerts its hepatoprotective effects via SIRT3 179. Pyrroloquinoline quinone, another natural product, can improve liver metabolic diseases through increasing the expression of SIRT3 180."

Ghmac profile image
Ghmac

Where do you get Palmitoylethanolamide that also has 180 mg of Honokiol?

Bolt_Upright profile image
Bolt_Upright in reply to Ghmac

I use this, it provides 2 600 mg doses a day but it is not ultra-micronized: amazon.com/gp/product/B0777...

So I also have 600 mg of this in the middle of the day: amazon.com/gp/product/B07NJ...

P1800 profile image
P1800

Does anyone know anything about using this when your on the usual PD medication?

I am looking for the most reputable brand of Honokiol. Compared to most companies, I trust pure encapsulations and Thorne. But, although these contain Magnolia Bark, the amount of Honokiol is not clear. Can someone please help me? And wouldn’t the B vitamins , thiamin especially) (not niacin) cause insomnia ?

Source of some info

nootropicsexpert.com/magnol...

Thorne
Bolt_Upright profile image
Bolt_Upright in reply to

Park Bear found this. Too pricey for me, but is supposed to be all Honokiol: amazon.com/EcoNugenics-Hono...

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