Nobiletin

Mauritio

Nobiletin is an interesting flavonoid with some pro-metabolic benefits.

Ray Peat mentioned it as a useful supplement for mTOR inhibition:

"Several substances block the increase of mTOR, including the citrus flavonoid nobiletin, aspirin, and progesterone."
-Ray Peat's Newsletter, Q2 2022, "Aging, Energy, Progesterone"

And also as an anti-inflammatory agent derived from citrus fruits:

"Choosing foods that contain substances that protect against the many known pro-inflammatory, age-accelerating processes is relatively simple—citrus fruits, for example, contain a great variety of substances related to nobiletin, naringin, fisetin, and quercetin"
-January 2021 - Ray Peat's Newsletter

KEY BENEFITS :

Lowers inflammation and oxidative stress
Regulates circadian rhythm
benefits mitochondria and ETC
Anti-histamine

USER EXPERIENCES:

1.https://www.reddit.com/r/NootropicsDepot/comments/w3n0bb/why_is_nobiletin_so_good/?rdt=61390

2.https://www.reddit.com/r/NootropicsDepot/comments/yd6r13/updated_experience_with_nobiletin/

3.https://nootropicsdepot.com/nobiletin-powder-citrus-aurantium/#product-reviews

Mauritio

It increases healthy aging, ATP Production and helps with mitochondria and the ETC.

It did not affect weight, but older mice had fully restored glucose control when fed nobiletin.
It also increased body temperature and heat tolerance in old mice.

Nobiletin led to a twofold increase in distance run/day on voluntary wheels! So it seems to be good for activity and muscle health.

The NAD/NADH ratio was increased in old muscles as well, showing a shift towards oxidative phosphorylation.

In a high fat diet scenario nobiletin was able to rescue a lot of the parameters and increase oxygen consumption, heat production and UCP1 expression, while lowering inflammatory cytokines like TNFa.

As I understand it most of these effects are medicated through the ROR (retinoid acid receptor-related orphan receptor)

"Furthermore, NOB enhances healthy aging in mice fed with a high-fat diet (HF). In HF skeletal muscle, the NOB-ROR axis broadly activates genes for mitochondrial respiratory chain complexes (MRCs) and fortifies MRC activity and architecture, including Complex II activation and supercomplex formation. These mechanisms coordinately lead to a dichotomous mitochondrial optimization, namely increased ATP production and reduced ROS levels."
https://www.nature.com/articles/s41467-019-11926-y#Fig

Mauritio

Nobiletin helps with fatty liver by lowering inflammation and oxidative stress via NfKb opposition.
https://pubs.acs.org/doi/pdf/10.1021/acs.jafc.3c06498

Sunniva

@Mauritio said in Nobiletin:

but older mice had fully restored glucose control when fed nobiletin

Do you have the study?

Mauritio

@Sunniva it's linked in the post you quoted

Mauritio

Nobiletin increases testosterone and lowers estrogen.

In this in vitro study nobiletin increases testosterone:

"Furthermore, we found that these compounds enhanced testosterone production via cyclic AMP (cAMP)/cAMP response element binding protein signalling. In particular, the compounds inhibited activation of phosphodiesterase and thereby increased production of cAMP. These findings support the possibility that K. parviflora extract, 5,7-dimethoxyflavone, and nobiletin may mitigate age-related disease and hypogonadism by enhancing testosterone production."

https://www.researchgate.net/publication/306926144_Effect_of_Kaempferia_parviflora_extract_and_its_polymethoxyflavonoid_components_on_testosterone_production_in_mouse_testis-derived_tumour_cells

Nobiletin lowers estrogen by inhibiting aromatase.
https://pubmed.ncbi.nlm.nih.gov/28177754/

Mauritio

It increases dopamine .

"MPTP-induced reduction of dopamine contents in the striatum and hippocampal CA1 region was improved by nobiletin administration (50mg/kg i.p.). Acute intraperitoneal administration of nobiletin also enhanced dopamine release in striatum and hippocampal CA1,..."

https://pubmed.ncbi.nlm.nih.gov/24316474/

NOB could restore memory impairment via the improvement of neurogenesis by ameliorating neuroinflammation in the hippocampushttps:

//pmc.ncbi.nlm.nih.gov/articles/PMC10181043/

Mauritio

"Nobiletin and tangeretin potently inhibited scratching behavior, as well as histamine-induced vascular permeability."

https://pubmed.ncbi.nlm.nih.gov/23938254/

Mauritio

Nobiletin for fatty liver:

Helps with fatty liver and fibrosis via increasing adiponectin and SOD while lowering MDA
https://pubmed.ncbi.nlm.nih.gov/38073108/
Helps via modulating Nrf2
https://pubmed.ncbi.nlm.nih.gov/38073108/
Helps via altering the gut microbiome
https://pubmed.ncbi.nlm.nih.gov/37139957/
Helps via lowering oxidative stress and lipid peroxidation and increasing ATP.
https://pubmed.ncbi.nlm.nih.gov/34695558/
Helps via increasing cholesterol to bile acids conversion ( increasing CYP7A1, and CYP27A1), increasing SCD1 and LXRa and lowering FAS.
So should be good for people with high cholesterol ,low bile production/flow.

https://pubmed.ncbi.nlm.nih.gov/36985541/