The 8+ Benefits Of J147: A Potent Curcumin Derivative (And How To Make T-006)

Unlike the current drugs approved for Alzheimer's Disease, J147 is neither an acetylcholinesterase inhibitor nor a phosphodiesterase inhibitor, yet it enhances cognition with a short-term treatment.

In this post, we will discuss how the curcumin derivative J147 improves memory and I'll explain a very powerful alternative way to get its benefits.

Basically, J147 (CAD-031) is a Curcumin and Cyclohexyl-Bisphenol A (CBA) derivative that is a potent neurogenic and neuroprotective drug. R R 

It was developed for the use of treating neurodegenerative conditions associated with aging. R

Curcumin is a polyphenol and the active component of Turmeric and Ginger.

Curcumin has many proven benefits in treating numerous diseases, but due to its poor ability to cross the Blood-Brain Barrier (BB), there are clear limitations.

J147 can cross the BBB into the brain (strong) and induce neuronal stem cell production. R R

1. Improves Mitochondrial Function And Longevity

J147 is very effective in preventing oxidative stress and improving mitochondrial function. R

For example, J147 increases mitochondrial function by improving ATP levels (inhibiting ATP synthase, specifically ATP5A). R

By inhibiting ATP synthase, J147 can reduce toxic metabolites that cause excitotoxicity. R

This allows for more healthy/younger mitochondria (on a molecular level by modulating the AMPK/mTOR pathway). R

For example, fruit flies that were given J147 had a longer lifespan (9.5-12.8%) due to the effects on mitochondria. R

J147 can also reduce aging of the brain from use of γ-glutamyl amino acids and BCAAs. R

2. Prevents Alzheimer's Disease 

J147 reverses cognitive impairment in a mouse model of Alzheimer’s Disease (AD). R

J147 can improve Amyloid-Beta (Aβ) metabolism and reduce levels in the brain by reducing protein levels of β-Secretase (BACE). R 

In animal models of AD, J147 can protect BBB permeability homeostasis and improve vascular function in the brain. R

J147 can also significantly increase levels of Docosahexaenoic Acid (DHA) in the brain. R

It can also restore Glutamate levels (synthesized from the TCA intermediate α-ketoglutarate) in the brain. R

3. Improves Memory

It enhances memory in both AD mice and normal aged animal models. R

Even in very old animal models, J147 can reverse severe cognitive deficits. R

J147 can also improve spatial memory and enhance Long-Term Potentiation (LTP). R

4. Grows The Brain

J147 can improve synaptic plasticity in the brain and induce its growth. R

J147 improves synaptic plasticity by maintaining the expression of Synaptophysin (a synaptic vesicle protein that is reduced in both aging and AD and is considered a biomarker for synapse loss). R

J147 grows the brain by increasing levels of both Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF). R

A  synthetic derivative of J147, T-006 (more discussed below on how to make it),  can also improve neurite outgrowth by regulating the PI3K/AKT pathway and increasing NGF levels. R

5. Protects Neurons

J147 does not specifically need BDNF to be neuroprotective. R  

J147 also rescues neurons Glutathione (GSH) depletion. R

J147 is also neuroprotective against glucose starvation. R

In AD brain's, Heme Oxygenase 1 (HO-1) as a pro-oxidant, instead of an antioxidant, while 5-Lipoxygenase (5-LOX) recruits other immune cells to induce an inflammatory response. R

J147 is able to reduce HO-1 levels and inhibit 5-LOX. R

T-006 at very low concentrations can rescue neurons from death (prevents reactive oxidative/nitrogen species stress in brain and glutamate-induced excitotoxicity). R

T-006 also inhibits NMDA overactivation, making it 100 times more potent than Memantine. R

6. May Improve Diabetes

In animal models, J147 has shown to decrease blood Glucose and HbA1c levels by increasing AMPK. R

Although not significant, J147 may also enhance the function of residual beta cells in diabetes. R

7. Fights Pain And Neuropathy

In an animal model with type 1 diabetes, J147 was shown to effective in treating Diabetic Neuropathy. R

It was also able to significantly improve diabetes-induced motor nerve dysfunction, peripheral sensitivity, and pain levels. R

8. May Improve Anxiety

J147 may have some potential in improving Anxiety levels. R R

In animal models with AD, J147 was able to improve anxiety levels during maze tests. R

J147 can be bought online from certain vendors, but as far as I know, none of the reasonably priced ones are are trustworthy.

I am doing my due diligence to acquire a good source for a reasonable price and will update in the future on a place to buy it.

If you do want to spend $$$ on J147, it goes for around 10 mg / $165, but since this is a biohacking website, let's talk about my biohacked alternative: T-006.

A more effective version called T-006 when combining tetramethylpyrazine and J147 (taking a methoxyphenyl group of J147 replacing it with tetramethylpyrazine). R

So here is what you need to make my more effective alternative to J147:

• Curcumin (as Turmeric and Ginger) - I like to use this combo as a supplement 
• Tetramethylpyrazine (as Ligusticum wallichii or Chocolate and Natto)
• Other Ingredients If Making Food-Version (Black Pepper, Stevia, Salt)

You can either supplement both or make them into a food (both have different effects for me).

If you are going to supplement:

• J147 metabolizes into CAD-31 in the brain.
• CAD-31 enhancing the use of free fatty acids for energy production by shifting of the metabolic profile of fatty acids toward the production of ketone bodies, a potent source of energy in the brain when glucose levels are low. R
• Thus you could supplement Ketones (empty stomach in morning) or go on a Ketogenic Diet

To make the food version (1 week supply):

1. Melt 3 bars of Dark Chocolate with 3 tbsp of Coconut Oil in pot or saucepan
2. Add 2 tbsp of this specific powdered Natto to chocolate
3. Add 2 tbsp of Turmeric, 2 tbsp of Ginger, 2tsp of Black Pepper powder (can add pinch of Salt or Stevia for sweetness)
4. Let cool (and eat) or freeze then eat/snack

Effects of supplementing for T-006 (exp over 1 month):

1. Increased mental clarity
2. Increased memory
3. Improved vision and smell

Effects from food version of T-006 (exp over 3 months):

1. Reduced brain fog
2. Increased overall energy 
3. Increased verbal fluency/acuity
4. Calmer stomach
5. Better stools

J147 is safe in animal studies (not genotoxic) and orally active. R R

For example, when J147 was fed at 10 mg/kg/day throughout pregnancy to mice, offspring were normal. R

Simple:

• Increases APP R
• Increases AMPK R
• Increases BAX (T-006 only) R
• Increases BCL-2 (T-006 only) R
• Increases BDNF R
• Increases CAMP R
• Increases CREB R
• Increases Drebrin R
• Increases Egr1 (2.5x) R
• Increases Egr3 (8.0x) R
• Increases Ketones Levels R
• Increases NGF (2.8x) (as well as T-006) R R
• Increases LTP R
• Increases PKA R
• Increases Spred2 (2.7x) R
• Increases Synapsin 1 R 
• Increases Synaptophysin R
• Increases TRKB R
• Reduces AKT (T-006 only) R
• Reduces BACE R
• Reduces ERK (T-006 only) R
• Reduces GFAP R
• Reduces Glucose R
• Reduces GSK3β (T-006 only) R
• Reduces HbA1C R
• Reduces HO-1 R
• Reduces HOP R
• Reduces HSP70 R
• Reduces HSP90 R
• Reduces iNOS R
• Reduces JNK R
• Reduces MAPK (T-006 only) R
• Reduces MEK (T-006 only) R
• Reduces mTOR R
• Reduces NMADR (T-006 only) R
• Reduces RNS (T-006 only) R
• Reduces ROS (T-006 only) R
• Reduces SAPK R
• Reduces TNFa R
• Reduces TSPO R
• Reduces 5-LOX R

Advanced:

• J147 is a phenyl hydrazide derived from the natural compound curcumin.
• J147 has a half-life of 2.5 hrs in the brain, 1.5 hrs in plasma, 4.5min in human microsomes, and <4min in mouse microsomes. R
• Chronic oral treatment with J147 protected the sciatic nerve from progressive diabetes-induced slowing of large myelinated fiber conduction velocity while single doses of J147 rapidly and transiently reversed established touch-evoked allodynia.
• J147 treatment down-regulated BACE, thus increasing APP (improper APP cleavage eventually gives rise to Aβ). R
• The mitochondrial α-F1 subunit of ATP synthase (ATP5A) as a high affinity molecular target of J147, a protein previously studied in the context of aging...has dose dependent inhibition on ATP5a. R
• J147 restored the levels of acylcarnitines suggesting a positive effect on mitochondrial dynamics. R
• In NMDA receptors, T-006 inhibits excessive Ca2+ influx. R
• T-006 has a protective role in this system through both inhibiting MAPK/ERK pathway and restoring PI3-K/Akt pathway. R

• Other derivatives such as 3j (dicyanovinyl-substituted J147 analogue) can inhibit oligomerization and fibrillation of β-amyloid peptides and protects neuronal cells from β-amyloid-induced cytotoxicity. R