101 replies to this topic

[Bateau]

I don't think this article gets it right. So NALT isn't a good precursor for tyrosine, but we are not taking it for that. There might be other pathways. Also I don't find their claim that it doesn't cros the BBB backed up in their cited papers. The article claims that 74 +23 % is lost in the urine and leave out that is only about 10% of the supplemented NALT.

In my experience NALT feels quite dopaminergic and has fewer side effects than plain tyrosine.

The author never claims that NALT doesn't cross the BBB.

Did you read all the references?

HED of 1.25 grams has no effect on serum tyrosine levels? INJECTING 5 grams has a 25% increase? Lackluster, to put it lightly, compared to L-Tyrosine or L-Phenylalanine.

N-acetyl-l-tyrosine and N-acetyl-l-cysteine as tyrosine and cysteine precursors during intravenous infusion in humans

The usefulness of N-acetyl-l-tyrosine (NAT) and N-acetyl-l-cysteine (NAC) as tyrosine and cysteine precursors during intravenous infusion was investigated in humans. Plasma levels and urinary excretion of NAT, tyrosine, NAC, and total cysteine were determined, and the site of deacetylation was examined by measuring the splanchnic and renal balances. Eleven healthy volunteers were given 5 g of either NAT or NAC as a 4-hour intravenous infusion. Plasma levels of NAT and NAC increased rapidly, accompanied by a 25% increase in tyrosine levels and a 35% decrease in total cysteine. Urinary excretion of NAT and NAC in 4 hours accounted for 56% and 11% of the infused amount, respectively. No net production of tyrosine or cysteine was found from the splanchnic area, but from the kidneys there was a small release of both tyrosine (10 ± 3 μmol/min) and cysteine (64 ± 3 μmol/min). We conclude that under these conditions the usefulness of NAT and NAC as precursors for the corresponding amino acids in humans is not apparent.

Brain tyrosine increases after treating with prodrugs: comparison with tyrosine

After mice had been treated with L-tyrosine, O-phospho-L-tyrosine, L-tyrosine methyl ester or N-acetyl-L-tyrosine, tyrosine was assayed by HPLC coupled with fluorometric detection. O-Phospho-L-tyrosine behaved as a tyrosine prodrug after its hydrolysis by acid and alkaline phosphatases. After the intraperitoneal administration of O-phospho-L-tyrosine or the methyl ester, there was a substantial increase in bioavailability in terms of the effect of tyrosine. The two prodrugs were as powerful as tyrosine following oral administration. N-Acetyl-L-tyrosine was the least effective prodrug tested. The stability, solubility and bioavailability of O-phospho-L-tyrosine are consistent with proposing it for use as a tyrosine prodrug. In addition, it can be used parenterally. The use of a tyrosine aminotransferase inhibitor is necessary for limiting the hepatic breakdown of tyrosine and for increasing its bioavailability.

Edited by Bateau, 22 December 2013 - 10:29 AM.

[airplanepeanuts]

The author never claims that NALT doesn't cross the BBB.

Yes he does in the summary.


About the serum tyrosine level: as I said this is not relevant. If you want tyrosine in your blood just take l-tyrosine, which is absorbed just fine.

Edited by airplanepeanuts, 22 December 2013 - 10:53 AM.

[Bateau]

O.K...

For those that take N-acetyl L-Tyrosine with the intention of it being a source of tyrosine....

Utilization of tyrosine-containing dipeptides and N-acetyl-tyrosine in hepatic failure.

The impact of hepatic dysfunction on the elimination and hydrolysis of three potential tyrosine sources for total parenteral nutrition, the dipeptides L-alanyl-L-tyrosine (Ala-Tyr) and glycyl-L-tyrosine (Gly-Tyr), and N-acetyl-L-tyrosine (Nac-Tyr) were evaluated in six patients with hepatic failure (five chronic, one acute) and seven healthy subjects. In controls, whole-body clearance (Cltot) of Ala-Tyr was higher than of Gly-Tyr (3,169 +/- 214 vs. 1,780 +/- 199 mL/kg/min, P < .01), and both exceeded clearance of Nac-Tyr (309 +/- 29 mL/kg/min, P > .01). Both dipeptides were hydrolyzed and released tyrosine immediately. In hepatic failure, elimination and hydrolysis of Ala-Tyr and Gly-Tyr were comparable to controls, but Cltot of Nac-Tyr was reduced (236 +/- 26 mL/kg/min). Neither in controls nor in patients an increase in plasma tyrosine concentration was seen after Nac-Tyr, and the major part of Nac-Tyr infused was lost in urine. The Cltot of tyrosine as evaluated after Ala-Tyr infusion (with the immediate release of tyrosine) was severely reduced in hepatic failure (152.7 +/- 38.4 vs. 484.4 +/- 41.4 mL/kg/min, P < .001) and half-life (kle) was retarded from 14.4 +/- 1.4 to 90.2 +/- 32.2 minutes (P < .03). The authors conclude that acute and chronic hepatic dysfunction does not affect elimination and hydrolysis of the dipeptides Ala-Tyr and Gly-Tyr and the constituent amino acids are released immediately. Nac-Tyr elimination was not grossly affected by hepatic failure, but neither in healthy subjects nor in hepatic failure patients was an increase of tyrosine seen. Both dipeptides but not Nac-Tyr may serve as a tyrosine source in parenteral nutrition. Moreover, by its rapid hydrolysis, the use of Ala-Tyr, for the first time, enables a simple rapid nonisotope evaluation of tyrosine kinetics for assessment of liver function.

Utilization of tyrosine dipeptides and acetyltyrosine in normal and uremic humans.

The impact of renal failure on the elimination and hydrolysis of three sources of tyrosine for parenteral nutrition, the dipeptides alanyltyrosine (Ala-Tyr), glycyltyrosine (Gly-Tyr), and N-acetyltyrosine (NAc-Tyr) was investigated in eight patients on regular hemodialysis therapy (HD) and seven healthy controls (CON). In CON, whole body clearance (Ctot) of Ala-Tyr (3,169 +/- 198 ml/min) was higher than Gly-Tyr (1,781 +/- 184, P less than 0.001), and both exceeded NAc-Tyr (284 +/- 24, P less than 0.001). In HD, Ctot of Ala-Tyr was not different from CON, but Ctot of Gly-Tyr (858 +/- 73, P less than 0.001) and NAc-Tyr (129 +/- 30, P less than 0.02) was decreased. The rise in plasma levels of constituent amino acids was higher in Ala-Tyr vs. Gly-Tyr (P less than 0.01). In HD, the pattern was similar, although the increase in Tyr was less than in CON. Plasma Tyr did not increase with NAc-Tyr in either group. Urinary loss of peptides was neglible, but 60% of NAc-Tyr infused was excreted by CON. The half-life of peptides incubated in CON and HD plasma was unchanged for Ala-Tyr (12.3 +/- 0.9 vs. 14.6 +/- 1.9 min) and prolonged for Gly-Tyr in HD (101.7 +/- 4.9 vs. 131.3 +/- 12, P less than 0.05). Thus renal failure does not impair Ala-Tyr disposal and delays Gly-Tyr utilization. These differential effects on peptide assimilation underscore the importance of peptide structure on metabolism. Both peptides, but not NAc-Tyr, may serve as a nutritional substrate in renal failure patients.

I don't see how this could be discussed any further in a scientific manner...

Edited by Bateau, 22 December 2013 - 12:23 PM.

[airplanepeanuts]

My advice would be to try NALT, which I think is great especially combined with other stuff for example Ginseng. L-Tyrosine has a noticable dopamine effect, too. But tolerance sets in pretty much immediately for me. Also it has side effects like headache, irritability that I don't get with NALT at all.

[Reformed-Redan]

L-Tyrosine alone is good stuff. DLPA I believe breaks down eventually into PEA, so it's got more of a rushy feeling.

[Multicultural Harmony]

What about a rotigotine transdermal patch to get your dopamine fix? lol.

[airplanepeanuts]

O.K...

For those that take N-acetyl L-Tyrosine with the intention of it being a source of tyrosine....

I don't see how this could be discussed any further in a scientific manner...

Well, according to the abstract NALT was the least effective of the prodrugs tested to increase brain tyrosine. That does not mean that it is ineffective.
On the other hand it might actually be good that NALT doesn't raise blood levels of tyrosine as much as l-tyrosine, because high levels might be the cause of side effects and rapid tolerance.

Finally is the whole brain tyrosine content (of mice) really the whole picture? I am not sure. I am not a biochemist by the way.

[Bateau]

Bateau, what form/brand of Jiaogulan do you take, and what dosages?

Also, what studies show Jiaogulan is: "the 2nd most potent supplement at increasing insulin sensitivity in humans"

What is the human HED for the effects of Jiaogulan to be effective? Thanks.

I take the Solaray brand that has 410 mg of gypenosides per pill IIRC which with one pill should put you well into the HED of 1.62 - 4.86 mg/kg gypenosides for dopaminergic effects as inferred by these studies.

R.E. Jaiogulan's ability to increase insulin sensitivity, this is inferred from these 3 studies in which jiaogulan was given as a tea compared to green tea which was called a "placebo" in each study, however I think we can all agree that adding cups of green tea every day to a diabetics regimen will effect health parameters and is therefore a terrible placebo. Regardless, jiaogulan tea was able to blow green tea out of the water in its ability to improve vital metabolic parameters of diabetics (insulin sensitivity, pancreatic insulin secretion, fasting insulin levels, fasting glucose levels HbA1C, AUC blood glucose response, etc.) Many of the things that green tea extract is often taken for.

This study in non diabetics with NAFLD is also pretty eye opening however it uses an actual concentrated extract instead of the weak aqueous extract (tea) that the other studies use.

Either way the data implies that the effective dosage to receive the benefits of jiaogulan are pretty low and easy to achieve with either dietary addition or supplementation.

Edited by Bateau, 28 December 2013 - 09:20 PM.

[nupi]

Bacopa and N-Acetyl-Cysteine will also have very little acute effects and only have significant effects when taken chronically. Both could be used to help mitigate the side effects of substance issues as well as mitigate types of manic episodes. Chronic supplementation with Bacopa reduces anxiety and improves memory, the perfect supplement for a person suffering from memory loss, anxiety, mood swings and cravings due to substance issues (cannabis and caffeine included). Ayurveyda got it right when it crowned Bacopa as the overall best 'brain tonic'.

I find it a little weird to have Bacopa on a list of Dopaminergics and the claim of little acute effects is a bit dubious, too. Personal experience with Bacopa (different brands, too) would very much suggest it to be primarily serotonergic with little to no DA mediated effect. In fact, with prolonged use it even has similar side effects as SSRIs (if perhaps weaker but then again the effects are weaker, too). I can also feel it within an hour or two of ingesting it, much like I can with Escitalopram (the SSRI posterchild). About the memory improvements, I never noticed any real impact there but given that SSRIs are known to increase neurogenesis, I might buy the argument in principle.

I like Jiaogulan a lot but it tends to poop out after repeated use fairly quickly...

Edited by nupi, 29 December 2013 - 11:33 AM.

[666illuminati]

Damn sam what a find. Heres a herb i stumbled upon while researching chinese herbs for adrenal fatigue, and it just so happens to have dopamine neuron protective properties
http://en.wikipedia.org/wiki/Rehmannia

[666illuminati]

http://www.naturalst...ws200707049.asp
shit like this gets me pumped son ahhhhhhh

[Bateau]

Name: Chaenomeles speciosa
Type: dopamine reuptake inhibitor.
http://en.wikipedia....omeles_speciosa

Great find Lemon, +1

Extracts of Fructus akebiae contain hederagenin, which is a SNDRI according to one study http://www.sciencedi...09130571100323
I purchased a non-standardized whole extract of F.A. from ActiveHerb.com and used it for about a month with notable but not overwhelming results. It seemed to cause a bit of anxious energy, maybe a bit too stimulating, but I take too many other things to have really given it a good shot on its own.

Very interesting find, another article at High Tower Pharmacology suggested that hederagenin is likely to have little access across the BBB, but at least one rat study and the traditional medicinal uses of Fructus Akabiae suggest that it has some ability to cross the BBB, however it may be that large amounts are necessary for significant effects.

What was the brand of 'Ba Yue Zha' you used? +1

Edited by Bateau, 30 December 2013 - 11:42 PM.

[deeptrance]

...the traditional medicinal uses of Fructus Akabiae suggest that it has some ability to cross the BBB, however it may be that large amounts are necessary for significant effects.

What was the brand of the extract you used and where did you source it? +1

Right, it's possible (as always) that any effects I noticed were placebo. I had to consume more than a gram to get it to the level where it seemed to affect me. It's effects were rather unique, which leads me to believe it wasn't placebo, and they were potentiated by other related substances. For example, I became very uncomfortable when I combined FA with anything that significantly increases serotonin activity, whether via MAO inhibition, reuptake inhibition, or agonism of certain 5ht receptors. But I didn't notice any complications with serotonin precursors.

The extract was purchased from ActiveHerb.com, as mentioned in my original post on the subject. I would still like to try Axon, but the company that developed it seems to have pulled it from their offerings and now it's only available through one other source at a steeply discounted price.

I wish I could comment specifically on the dopaminergic properties of hederagenin but I've never seen any data on its affinity for any of the monoamine transporters, only the blanket statement that it's a reuptake inhibitor of S, NE, and DA.

[tritium]

Interestingly, Jiaogulan is also contained in a product called "ImmortaliTea", possibly since it is regarded as the "immortality herb" in traditional Chinese medicine.

[Bateau]

Round Two

I figured that Jiaogulan couldn't be the only supplement shown to have regenerative properties for the dopaminergic system, so I did some digging and found some dirt. 6 new neuroregenerators, 2 very promising, 2 promising, and 2 duds (listed in that order). I've also included 2 other dopaminergics, one is a promising SNDRI with lots of traditional human use but seriously lacking in scientific trials, the other is essentially completely unstudied all-around, making for a total of 8 new dopaminergics.


Stereospermum suaveolens - An incredibly understudied medicinal tree used in Ayurveda with all parts containing medicinal properties. Had by far the most significant regenerative effects to the dopaminergic system out of all these second round supplements, giving Jiaogulan a run for its money, although the dose may be a bit impractical (unlike Jiaogulan). Has understudied neuroregnerative [1], neuroprotective [2], hepatoprotective [3], gastroprotective [4], antihyperglycemic [5], antioxidant [5], antipyretic [6], anti-inflammitory [7], and analgesic [6] properties. Seems to also offer some pretty significant stimulatory effects that doesn't seem to have standard tolerance issues (see data from study below), since by day 30 most of the rats treated with the medium to high doses of S. suaveolens were more active than the sham group, and this level of activity continued to increase all the way to the end of the study at 42 days. Very interesting plant to say the least.

Objectives: To evaluate the neuroprotective effect of Stereospermum suaveolens DC on 6-hydroxy dopamine induced Parkinson's disease model.
Materials and Methods: The study was conducted on Sprague-Dawley rats where parkinson's disease was induced by producing the striatal 6-hydroxy dopamine lesions. The test animals received methanolic extract of Stereospermum suaveolens at dose of 125, 250 and 500 mg/kg for 42 days. Behavioral assessment, spontaneous locomotor activity and muscular coordination were studied. Antioxidant levels, striatal infraction area were assessed and histopathological studies were carried out.
Results: The Stereospermum suaveolens DC methanolic extract showed significant dose dependent increase in behavioral activity, improved muscular coordination. Significant reduction of lipid peroxidation (LPO), increased antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT) and non-enzymatic activity of glutathione (GSH) and total thiol levels in extract treated groups was observed in test groups as compared to control group. Striatal infarction area was significantly reduced in extract treated groups as compared to control group.
Conclusion: The methanolic extract of Stereospermum suaveolens DC showed neuroprotective activity against 6-hydroxy dopamine induced Parkinson's disease in rats.

http://www.ncbi.nlm....les/PMC3523502/


Uncaria rhynchophylla - Another plant used in Ayurveda that has shown neuroregnerative properties specifically for the dopaminergic system at very relevant oral doses. Seems to require the lowest dosage out of all supplements to achieve neuroregenerative effects and less seems to be more with this extract as a high dose showed less benefit than a low dose, unlike Jiaogulan or S suaveolens, both of which seem to have dose dependent effects. In-optimal dosing was used for testing, needs more scrupulous testing. Less impressive neuroregeneration than S. suaveolens or Jiaogulan, but still very promising.

While the hook of Uncaria rhynchophylla (URH) is a traditional herb used in northeast Asia for the treatment of Parkinson's disease (PD)-like symptoms such as tremor, it has not been experimentally evaluated in a PD model... We investigated the effects of URH on 6-hydroxydapamine (6-OHDA)-induced neurotoxicity in in vitro and in vivo models of PD. The cell viability, anti-oxidative activity, and anti-apoptotic activity of a water extract of URH (URE) were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, reactive oxygen species (ROS), total glutathione (GSH), and caspase-3 assays in PC12 cells stressed by 6-OHDA. We also investigated the behavioral recovery and dopaminergic neuron protection of URE using an apomorphine-induced rotation test and tyrosine hydroxylase immunohistochemistry in the hemi-parkinsonian rat model of the unilateral 6-OHDA lesion of the medial forebrain bundle... In PC12 cells, URE significantly reduced cell death and the generation of ROS, increased GSH levels, and inhibited caspase-3 activity induced by 6-OHDA. In 6-OHDA-lesioned rats, posttreatment with URE (5 mg/kg/day for 14 days) significantly reduced apomorphine-induced rotation, and it lowered dopaminergic neuronal loss in substantia nigra pars compacta... URE possesses neuroprotective activity against 6-OHDA-induced toxicity through anti-oxidative and anti-apoptotic activities in PD models

http://www.sciencedi...378874109005224


Black tea - Unknown whether or not green tea has the same effects, but at least one epidemiological study suggests that the effects are solely with black tea. Dose may be too high to be relevant, but epidemiological data suggests otherwise.

In the present study, an attempt has been made to explore the neuroprotective and neuroreparative (neurorescue) effect of black tea extract (BTE) in 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD). In the neuroprotective (BTE + 6-OHDA) and neurorescue (6-OHDA + BTE) experiments, the rats were given 1.5% BTE orally prior to and after intrastriatal 6-OHDA lesion respectively. A significant recovery in d-amphetamine induced circling behavior (stereotypy), spontaneous locomotor activity, dopamine (DA)-D2 receptor binding, striatal DA and 3–4 dihydroxy phenyl acetic acid (DOPAC) level, nigral glutathione level, lipid peroxidation, striatal superoxide dismutase and catalase activity, antiapoptotic and proapoptotic protein level was evident in BTE + 6-OHDA and 6-OHDA + BTE groups, as compared to lesioned animals. BTE treatment, either before or after 6-OHDA administration protected the dopaminergic neurons, as evident by significantly higher number of surviving tyrosine hydroxylase immunoreactive (TH-ir) neurons, increased TH protein level and TH mRNA expression in substantia nigra. However, the degree of improvement in motor and neurochemical deficits was more prominent in rats receiving BTE before 6-OHDA. Results suggest that BTE exerts both neuroprotective and neurorescue effects against 6-OHDA-induced degeneration of the nigrostriatal dopaminergic system, suggesting that possibly daily intake of BTE may slow down the PD progression as well as delay the onset of neurodegenerative processes in PD.

http://www.sciencedi...969996105003384


Oxyresveratrol - Found in mulberries, oxyresveratrol seems to have more promise than resveratrol r.e. neuroregeneration. In vitro evidence only, while all other previous supplements have had in vivo evidence to support dopaminergic restoration. Relevant dose unknown.

Oxyresveratrol (OXY) is a polyhydroxylated stilbene existing in mulberry. Increasing lines of evidence have shown its neuroprotective effects against Alzheimer disease and stroke. However, little is known about its neuroprotective effect in Parkinson disease (PD). Owing to its antioxidant activity, blood-brain barrier permeativity, and water solubility, we hypothesized that OXY may exert neuroprotective effects against parkinsonian mimetic 6-hydroxydopamine (6-OHDA) neurotoxicity. Neuroblastoma SH-SY5Y cells have long been used as dopaminergic neurons in PD research. We found that both pretreatment and posttreatment with OXY on SH-SY5Y cells significantly reduced the release of lactate dehydrogenase, the activity of caspase-3, and the generation of intracellular reactive oxygen species triggered by 6-OHDA. Compared to resveratrol, OXY exhibited a wider effective dosage range. We proved that OXY could penetrate the cell membrane by HPLC analysis of cell extracts. These results suggest that OXY may act as an intracellular antioxidant to reduce oxidative stress induced by 6-OHDA. Western blot analysis demonstrated that OXY markedly attenuated 6-OHDA-induced phosphorylation of JNK and c-Jun. Furthermore, we proved that OXY increased the basal levels of SIRT1, which may disclose new pathways accounting for the neuroprotective effects of OXY. Taken together, our results suggest OXY, a dietary phenolic compound, as a potential nutritional candidate for protection against neurodegeneration in PD.

http://www.ncbi.nlm....pubmed/18675900


EGb 761 (GinkGold) - Not any Ginkgo extract, but specifically EGb 761, commercially sold as GinkGold by Nature's Way. Personally not a fan due to potential increases in cancer, but it showed some fairly unimpressive ability to restore dopamine levels that normal ginkgo extract could not. Most benefits seem to be related to MAO inhibiton, as stated by authors.

The present study investigated the neuroprotective and neurorestorative effects of Ginkgo biloba extract (EGb 761) and its two components ginkgolides A (BN52020) and B (BN52021) in mice. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg/d i.p. for six days) significantly reduced striatal dopamine (DA) levels in C57 mice measured by high performance liquid chromatography with electrochemical detection (HPLC-EC). When C57 mice were pretreated with EGb 761 (20, 50, 100 mg/kg/d i.p.) for 7 days and then treated with the same extract 30 min before MPTP injection for 6 days, the neurotoxic effect of MPTP was antagonized in a dose-dependent fashion. Similar treatment with ginkgolides A and B (5, 10, 50 mg/kg/d i.p.) showed no protective effect. When C57 mice were treated with EGb 761 (50 mg/kg/d i.p.) after MPTP-lesion, the recovery of striatal dopamine (DA) levels was accelerated. However, similar treatment with ginkgolides A or B (10 mg/kg/d i.p.) did not show any effect. EGb 761, but not ginkgolides A and B, nonselectively inhibited mouse brain MAO activity in vitro (IC50 = 36.45 +/- 1.56 microg/ml) tested by an improved fluorimetric assay. The results demonstrate that EGb 761 administered before or after MPTP treatment effectively protects against MPTP-induced nigrostriatal dopaminergic neurotoxicity and that the inhibitory effect of EGb 761 on brain MAO may be involved in its neuroprotective effect.

http://www.ncbi.nlm....pubmed/10416821


Vitamin D3 - Another reason to take Vitamin D. Results are unimpressive, as with ginkgo.

It has previously been demonstrated that 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] administration, whether in cell cultures or in vivo to rats, increases glial cell line-derived neurotrophic factor (GDNF) expression levels, suggesting that this hormone may have beneficial effects in neurodegenerative disorders. This study was carried out to explore the effects of 1,25(OH)(2)D(3) administration in a 6-OHDA-lesioned rat model of Parkinson's disease on GDNF and tyrosine hydroxylase (TH) expression in substantia nigra (SN) and striatum. Two groups of animals received 1,25(OH)(2)D(3) intraperitoneally, the first group 7 days before the unilateral injection of 6-OHDA into the medial forebrain bundle (MFB) and the second group 21 days (days 21-28) after the unilateral injection of 6-OHDA. Animals of both groups were sacrificed on day 28. In addition, two other groups received a unilateral injection of either saline or 6-OHDA into the MFB. Rats were killed, and the SN and striatum were then removed for GDNF and TH determination. Striatal GDNF protein expression was increased on the ipsilateral with respect to the contralateral side after 6-OHDA injection alone as well as in 1,25(OH)(2)D(3)-treated rats before or after 6-OHDA administration. As expected, 6-OHDA injection induced an ipsilateral decrease in TH-immunopositive neuronal cell bodies and axonal terminals in the SN and striatum. However, treatment with 1,25(OH)(2)D(3) before and after 6-OHDA injection partially restored TH expression in SN. These data suggest that 1,25(OH)(2)D(3) may help to prevent dopaminergic neuron damage.

http://www.ncbi.nlm....pubmed/18816795


Sideritis scardica - another natural SNDRI, commonly consumed in the Mediterranean as a tea. This plant seems to have a wide variance in its natural chemical constituents [1], making for potentially highly variable potency and effects from plant to plant. Has psychostimulant as well as antidepressant effects [2]. Also seems to have some decent potential as an antioxidant source [3], as well as anti-inflammatory, gastroporotective, and anti-cancer effects [4]. Between this, Jiaogulan, and black tea, green tea is looking lackluster r.e. dopaminergic teas.

Sideritis species are traditionally used within the Mediterranean area as teas, flavouring agents or for therapeutical purposes. The aim of this study was to investigate the effects of Sideritis scardica extracts on the monoamine transporters and to derive and explain possible medicinal applications from the pharmacological profile of the extracts. We have studied the effect of various S. scardica extracts on serotonin, noradrenaline and dopamine uptake in rat brain synaptosomes and serotonin uptake in human JAR cells. All extracts inhibited the uptake of all three monoamines into rat brain synaptosomes by their respective transporters, the alcoholic extracts being more effective than the water extract. EC(50) values were in the range of 30-40 μg/ml. Inhibition of the human serotonin transporter by the methanol extract was even more effective (EC(50) 1.4 μg/ml). Combining Sideritis ethanol extract and fluvoxamine resulted in a leftward shift of the fluvoxamine concentration-response curve. The pharmacological profile of S. scardica extracts as triple monoamine reuptake inhibitors suggests their use in the phytochemical therapy of mental disorders associated with a malfunctioning monoaminergic neurotransmission, such as anxiety disorders, major depression, attention-deficit hyperactivity disorder, mental impairment or neurodegenerative diseases

http://link.springer...2-0824-9#page-1


Cymbopogon schoenanthus - Essentially completely unstudied in all animals. Just throwing this in here for fun.

This study aimed to investigate the antistress properties of the ethanol extract of Cymbopogon schoenanthus (CSEE), growing wild in the southern part of Tunisia. The effect of extracts on H₂O₂-induced cytotoxicity and stress in human neuroblastoma SH-SY5Y cells. Its effect on stress-induced in ICR mice was exposed to force swim and tail suspension, in concordance with heat shock protein expression (HSP27 and HSP90), corticosterone, and catecholamine neurotransmitters level. Our results demonstrated that pretreatment of SH-SY5Y cells with CSEE at 1/2000, 1/1000, and 1/500v/v dilutions significantly inversed H₂O₂-induced neurotoxicity. Moreover, CSEE treatments significantly reversed heat shock protein expression in heat-stressed HSP47-transformed cells (42°C, for 90min) and mRNA expression of HSP27 and HSP90 in H₂O₂-treated SH-SY5Y. Daily oral administration of 100mg/kg and 200mg/kg CSEE was conducted to ICR mice for 2 weeks. It was resulted in a significant decrease of immobility time in forced swimming and tail suspension tests. The effect of CSEE on animal behavior was concordant with a significant regulation of blood serum corticosterone and cerebral cortex levels of catecholamine (dopamine, adrenaline, and noradrenaline). Therefore, this study was attempted to demonstrate the preventive potential of CSEE against stress disorders at in vitro and in vivo levels.

http://www.ncbi.nlm....48/#!po=55.0000

Edited by Bateau, 02 January 2014 - 05:51 AM.

[Galaxyshock]

Good finds.

Uncaria rhynchophylla is Cat's Claw and contains Rhynchophylline which is NMDA-antagonist, and the catechins work as MAO-B inhibitors.

Try searching for Shilajit, it should also be a dopaminergic.

Edited by Galaxyshock, 02 January 2014 - 10:06 AM.

[deeptrance]

...but it showed some fairly unimpressive ability to restore dopamine levels that normal ginkgo extract could not.

Vitamin D3 - Another reason to take Vitamin D. Results are unimpressive, as with ginkgo.

Thanks for all the time you've put into this great research!

Did you mean to say "fairly impressive" in the passages quoted above? In context, the use of the word unimpressive seems a bit odd.

Uncaria rhynchophylla is Cat's Claw and contains Rhynchophylline which is NMDA-antagonist, and the catechins work as MAO-B inhibitors.

It's true that Uncaria sp. are referred to as Cat's Claw but readers should note that virtually everything sold as Cat's Claw online is actually Uncaria tomentosa, which has many beneficial qualities but has very little of the MAO-B inhibition found via rhynchophylline. And there are many alternatives that are more effective for MAO-B inhibition anyway, so this wouldn't be a primary reason for consuming any species of Uncaria.

[Nobility]

Thank You for this thread and posts, REALLY GOOD.

• + REP
• + 5 Star Thread rating
• + 5 Star user rating.

[Bateau]

Interestingly, Jiaogulan is also contained in a product called "ImmortaliTea", possibly since it is regarded as the "immortality herb" in traditional Chinese medicine.

Just to split hairs, Jiaogulan was never accepted into Traditional Chinese Medicine, it falls more into Southern Chinese "folk medicine", where it was called the immortality herb like you mentioned.

Did you mean to say "fairly impressive" in the passages quoted above? In context, the use of the word unimpressive seems a bit odd.

No I meant to say UNimpressive.

It's all relative I suppose. I can see the argument be made that any supplement that shows any level of restorative ability to the dopaminergic system should be considered impressive, and I don't actively disagree with that. However the point that I was attempting to get across is that D3 and EGb 761 have so far shown significantly less impressive results than the 5 other neuroregnerative supplements that had been mentioned before them, those being the Jiaogulan, S suaveolens, U rhynchophylla, Black tea and Oxyresveratrol (Oxy admittedly needs some extrapolation and faith <see below>). Again, it's all relative. Was also attempting to not sound too sensationalist, can happen sometimes on this forum.

edit: I just realized that the Oxyresveratrol study is a 2008 study so the data implying that Oxy increases basal levels of SIRT1 may be false, due to complications with the Fleur de Lys that was used in all those stilbene/SIRT studies back then. Oxy may be less impressive than I assumed.

Edited by Bateau, 04 January 2014 - 05:58 PM.

[Nobility]

Type: Plant/Nature.
Action: L-DOPA
Work?: Yes it does, I will post studies below.
Dopamine?: Yes, it should effect dopamine in a positive way (most of the time..)

Q&A:
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Well, have a look around your town/city... You could get them in supermarkets, healthfood stores,etc... Or ask around...
If your town/city has stores like Asian/etc markets, they may stock them.

Best time?:
Starting Summer

Other?:
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Important Links: (PLEASE READ THEM) ****

• http://www.scienzave.../favabeans.html

OTHER:

- Sleep (AT LEAST 8 hours)
- Diet (ALWAYS eat a good breakfast)
- Exercise
- Limit sex/masturbation (e.g: if you orgasm EVERY day it may indeed cause you to become sluggish)
- If you drink extreme high amounts (high amounts of caffeine each day, it will effect you in a negative way. I was consuming massive amounts of coffee each day and it made me a train wreck).
- etc...

Focus on those, then if you wish, focus on supplements and all that, in my opinion.

- Dark Chocolate 85%+ (great booster)
-

Edited by Nobility, 06 January 2014 - 10:51 AM.

[agwoodliffe]

DO NOT touch Babchi with a barge-pole. It inhibits Mitochondrial Complex I, and is photocarcinogenic.

[Bateau]

DO NOT touch Babchi with a barge-pole. It inhibits Mitochondrial Complex I, and is photocarcinogenic.

Interesting opinion. How did you come to the conclusion that Psoralea is photocarcinogenic?

R.E. it's effects on inhibiting mitochondrial complex 1, it does that in cancer cells. In normal cells Psoralea has been shown to inhibit mitochondrial lipid peroxidation [1], mitochondrial dysfunction, and genomic damage caused by oxidative damage and AGING [2, 3, 4]. If that isn't sexy enough, it increases the amount of DEATH receptors for cancer (TRAIL) [5], enough to kill the notoriously tough-to-kill HeLa cells, as well as literally rip up cancer DNA [6].

Psoralea's not great on the testes, which is why I don't actively suggest it to people, but its way, way better than you're making it out to be. Even the lead researcher at Examine.com had this to say about it:

Possibly a good idea to pair this herb with Ganoderma lucidum (increases the immune factors that signal through this receptor and the other death receptor) and Theaflavins (increase the other death receptor, Fas). The three of them are unsupported currently as an over-the-counter anti-cancer prevention, but theoretically seems like a good idea

- Kurtis Frank

http://examine.com/supplements/Psoralea+corylifolia/

Edited by Bateau, 26 January 2014 - 11:00 PM.

[Bateau]

This conversation motivated me to look for any 2014 studies on Psoralea and I found this awesome study that would suggest that Psoralea could have Adaptogen-like properties.

Bidirectional regulation of bakuchiol, an estrogenic-like compound, on catecholamine secretion.

Excess or deficiency of catecholamine (CA) secretion was related with several diseases. Recently, estrogen and phytoestrogens were reported to regulate the activity of CA system. Bakuchiol is a phytoestrogen isolated from the seeds of Psoralea corylifolia L. (Leguminosae) which has been used in Traditional Chinese medicine as a tonic or aphrodisiac. In the present study, bovine adrenal medullary cells were employed to investigate the effects and mechanisms of bakuchiol on the regulation of CA secretion. Further, its anti-depressant like and anti-stress effects were evaluated by using behavioral despair and chronic immobilization stress models. Our results indicated that bakuchiol showed bidirectional regulation on CA secretion. It stimulated basal CA secretion in a concentration dependent manner (p<0.01), while it reduced 300μM acetylcholine (ACh) (p<0.01), 100μM veratridine (Ver) (p<0.01) and 56mM K(+) (p<0.05) induced CA secretion, respectively. We also found that the stimulation of basal CA secretion by bakuchiol may act through estrogen-like effect and the JNK pathway in an extra-cellular calcium independent manner. Further, bakuchiol elevated tyrosine hydroxylase Ser40 and Ser31 phosphorylation (p<0.01) through the PKA and ERK1/2 pathways, respectively. Bakuchiol inhibited ACh, Ver and 56mM K(+) induced CA secretion was related with reduction of intracellular calcium rise. In vivo experiments, we found that bakuchiol significantly reduced immobilization time in behavioral despair mouse (p<0.05 or 0.01), and plasma epinephrine (E) and norepinephrine (NE) levels in chronic immobilization stress (p<0.05). Overall, these results present a bidirectional regulation of bakuchiol on CA secretion which indicated that bakuchiol may exert anti-stress and the potential anti-depressant-like effects.

So it's a catecholamine reuptake inhibitor, the 4th most potent MAO-B inhibitor out of 905 plants, and a bidirection modulator of catecholamine release, as well as a potent and unique anti-cancer agent.

Edited by Bateau, 26 January 2014 - 11:31 PM.

[agwoodliffe]

Psoralen is the photo carcinogenic compound. Look it up.
The herb itself caused a lump to appear on my finger which still hasn't completely gone away.

[Bateau]

Psoralen is the photo carcinogenic compound. Look it up.
The herb itself caused a lump to appear on my finger which still hasn't completely gone away.

Ah, user bias. Better stay away from those figs then, considering they seem to be a much more potent source of Psoralen.

Can you not provide a link? A quick pubmed scan came up with nothing, and the wiki article references studies to bergaptene, a completely different psoralen (furocoumarin).

Edited by Bateau, 26 January 2014 - 11:38 PM.

[agwoodliffe]

And by the way, read the FULL study about Mitochondrial Complex 1. As you can see in the discussion, it clearly states: ''Chronic consumption (or enough intake) of Psoralea corylifolia L. could pos- sibly increase the risk of development of neurodegenerative diseases, assuming that these toxic agents can reach the brain ''.

Take from that what you will.

Attached Files

•  annals.1395.053.pdf   173.89KB   4 downloads

[Bateau]

And by the way, read the FULL study about Mitochondrial Complex 1. As you can see in the discussion, it clearly states: ''Chronic consumption (or enough intake) of Psoralea corylifolia L. could pos- sibly increase the risk of development of neurodegenerative diseases, assuming that these toxic agents can reach the brain ''.

Take from that what you will.

Not much to take from that.

Did you miss the studies I posted where Psoralea has been tested multiple times in normal cells and shows no sign of being a mitochondrial toxin? Rather it's been shown the be the opposite, a potent preserver of mitochondrial function, and actually prevents the very oxidative damage that the speculation you quoted is concerned about it causing.

This part:

In normal cells Psoralea has been shown to inhibit mitochondrial lipid peroxidation [1], mitochondrial dysfunction, and genomic damage caused by oxidative damage and AGING [2, 3, 4].

Check the links. Much better evidence than that pure speculation. There's no legitimate evidence that Im aware of that validates your concerns, whatsoever. No offense, seriously.

Edited by Bateau, 27 January 2014 - 03:16 AM.

[Barfly]

Hi, following this thread I have decided to try Jiogulan (Planetary herbals full spectrum extract) but after 2 weeks I still can't tell for sure if there are any benefits.

So I was wondering if perhaps this plant takes longer to take effect (like Bacopa) or can I safely assume at this point that Jiaogulan is not for me (looking for better mood and higher energy levels)

Also is there some any other plant that might give me a better chance of experiencing positive dopaminergic effects? ( I was thinking that maybe catuaba may give me a better bang for the buck than Jiaogulan?)

Thanks

[agwoodliffe]

And by the way, read the FULL study about Mitochondrial Complex 1. As you can see in the discussion, it clearly states: ''Chronic consumption (or enough intake) of Psoralea corylifolia L. could pos- sibly increase the risk of development of neurodegenerative diseases, assuming that these toxic agents can reach the brain ''.

Take from that what you will.

Not much to take from that.

Did you miss the studies I posted where Psoralea has been tested multiple times in normal cells and shows no sign of being a mitochondrial toxin? Rather it's been shown the be the opposite, a potent preserver of mitochondrial function, and actually prevents the very oxidative damage that the speculation you quoted is concerned about it causing.

This part:

In normal cells Psoralea has been shown to inhibit mitochondrial lipid peroxidation [1], mitochondrial dysfunction, and genomic damage caused by oxidative damage and AGING [2, 3, 4].

Check the links. Much better evidence than that pure speculation. There's no legitimate evidence that Im aware of that validates your concerns, whatsoever. No offense, seriously.

Interesting. Then comparing this with the study I read, something isn't quite adding up.

As for the photo-toxic aspect, the attached study gives some indication in the discussion. Not sure if it was the study I read on it 5 years ago though.

Ultimately, I will admit that this herb appears very attractive in what it can do. All I can say is, be on guard while trying it.

Attached Files

•  konglingdong-10.pdf   479.84KB   1 downloads

[agwoodliffe]

And the additional studies on the photo-effects of Psoralen are here:

Natl Cancer Inst Monogr. 1984 Dec;66:117-26.

Cutaneous phototoxicity due to psoralens.
Gange RW, Parrish JA.

Abstract
Psoralen phototoxicity has several features which distinguish it from other cutaneous responses to UV radiation, with or without an exogenous photosensitizing agent. Erythema resulting from psoralen phototoxicity shows a longer latent period between irradiation and onset, during which no visible cutaneous changes are present. The dose-response curve is steeper, with blistering reactions occurring in some subjects after as little as three to four times the minimum phototoxic dose of UV radiation at 320-400 nm (UVA). The acute phase of psoralen phototoxicity is followed by a more marked increase in epidermal pigmentation than is seen after most other phototoxic reactions or following UV irradiation alone. The pathways leading to the development of cutaneous phototoxicity have not been identified. The importance of the cross-linking of DNA as the initiating event is suggested but not proved by comparative data on different psoralen compounds with different cross-linking abilities and by wavelength-dependent selective photochemistry. The subsequent pathways leading to erythema and the mediators which are liberated have not been identified. In contrast to erythema induced by UVA and UV at 290-320 and at 220-290 nm (UVB and UVC, respectively), no evidence for the involvement of prostaglandins has been demonstrable. Histopathologic studies show changes in the epidermis and dermis, with damage to keratinocytes and an inflammatory infiltrate in the dermis, both of which occur later and are of longer duration than the damage induced by UVA, UVB, or UVC alone. Despite the widespread application of psoralen phototoxicity in humans in the form of PUVA treatment, much work remains to be done before we can elucidate the important mechanisms and pathways leading to the inflammatory and therapeutic responses which are induced in the skin. Improvement of our knowledge in this area is central to the evolution of safer and more effective forms of photochemotherapy.

PMID: 6531018 [PubMed - indexed for MEDLINE]

Proc Natl Acad Sci U S A. 1985 Sep;82(18):6158-62.

A possible mechanism of psoralen phototoxicity not involving direct interaction with DNA.
Laskin JD, Lee E, Yurkow EJ, Laskin DL, Gallo MA.

Abstract
Psoralens in combination with ultraviolet light (UVA; 320-400 nm) are used in the photochemical treatment of a variety of skin diseases including vitiligo, a skin depigmentational disorder, and psoriasis, a disease of accelerated epidermal cell proliferation. Although it is generally assumed that the major site of action of the psoralens is DNA, we have obtained evidence that another site may be the primary target for these compounds. We have identified specific, saturable, high-affinity binding sites for 8-methoxypsoralen on HeLa cells and have detected specific binding of 8-methoxypsoralen to four other human cell lines and five mouse cell lines. In HeLa cells, specific binding is reversible and independent of the ability of the compound to intercalate into DNA. In addition, binding sites become covalently modified by the psoralen after UVA exposure. Specific binding of 8-[methoxy-3H]methoxypsoralen constitutes 79% of the label bound to the cells. Scatchard analysis indicated two classes of psoralen binding sites: high-affinity sites with a Kd of 19 X 10(-9) M (1.8 X 10(5) sites per cell) and low-affinity sites with a Kd of 4 X 10(-6) M (7.1 X 10(6) sites per cell). Four structurally related psoralen analogs block 8-methoxypsoralen binding in a manner that parallels their biological activity. Based on these findings, we hypothesize that specific binding sites for psoralens on mammalian cells mediate, at least in part, psoralen-induced phototoxicity.

PMID: 3862124 [PubMed - indexed for MEDLINE]PMCID: PMC391011Free PMC Article

J Photochem Photobiol B. 1990 Jun;6(1-2):237-47.

Photocarcinogenicity of psoralens used in PUVA treatment: present status in mouse and man.
Young AR.

Institute of Dermatology, United Medical School of Guy's Hospital, University of London, U.K.

Abstract
There is good evidence that 8-methoxypsoralen is photocarcinogenic in psoriatic patients undergoing long-term photochemotherapy (PUVA) in the U.S.A. However, this conclusion has not been supported by two major European studies which have indicated that PUVA is a tumour promoter of damage initiated by other agents. Variation in PUVA treatment protocols in the U.S.A. and Europe may partly account for the different conclusions. There is much interest in the therapeutic potential of monofunctional psoralens. It is hoped that these may reduce long-term risk. Monofunctional and cross-linking psoralens have been shown to be photocarcinogenic in mouse skin. The relative risk of different compounds may be assessed in the mouse, but it is important to base comparisons on dose protocols that have been shown to be therapeutically effective.

PMID: 2121937 [PubMed - indexed for MEDLINE]

Again, just watch out.