28 replies to this topic

[PeaceAndProsperity]

I bought ALA (not R-ALA) 100mg and it seems to improve my vision and have some nice energizing effects.

Will it lose efficacy? Is there desensitization to its energizing effects?

[normalizing]

i did normal ala and i noticed positive effects too but i switched to r-ala because of its purported better benefits in comparison and what happened is, i dont even feel that one at all i just dont get it since the research is there, it is considered superior. something's not making sense...

[PeaceAndProsperity]

i did normal ala and i noticed positive effects too but i switched to r-ala because of its purported better benefits in comparison and what happened is, i dont even feel that one at all i just dont get it since the research is there, it is considered superior. something's not making sense...

Interesting. Could it have been a bad batch, since it's supposedly a very fragile molecule (or ala is)? What brand did you buy?

[normalizing]

ratherbeunknown this is second time i do this. long time ago i buy regular ala not sure of label was some basic one and it worked. then again im bamboozled by forum people and adverts online so i switch to r-ala, same result NOTHING. i did it just recently too and i should have known better but i was so convienced by the studies posted on this forum, i switched again to r-ala and im going to throw it out soon. please dont take my word for it tho, maybe i react differently, maybe it works for you so try and then decide. seriously, this is not good advice i dont advertise i wont put names of labels and its my own personal experience... but still something to consider, i guess.

[PeaceAndProsperity]

ratherbeunknown this is second time i do this. long time ago i buy regular ala not sure of label was some basic one and it worked. then again im bamboozled by forum people and adverts online so i switch to r-ala, same result NOTHING. i did it just recently too and i should have known better but i was so convienced by the studies posted on this forum, i switched again to r-ala and im going to throw it out soon. please dont take my word for it tho, maybe i react differently, maybe it works for you so try and then decide. seriously, this is not good advice i dont advertise i wont put names of labels and its my own personal experience... but still something to consider, i guess.

I probably won't buy it then, it's too expensive.

Maybe if there is a very cheap version (few capsules) I'd try it once but it seems none are cheap.

 

Today when I took ala sublingually (dropped the capsule content under my tongue) it literally felt like I had low blood sugar. I went shopping and came home eating but it didn't help, in fact eating slightly made it worse for a moment (suggesting high blood sugar).

Now it feels like I have too much oxygen in my head, the same feeling I get if I hyperventilate. I had this feeling yesterday when I tried it for the first time but it was a pleasant and energizing experience then. A strange sort of feeling. Still a bit dizzy and irritable (irritability being a part of low blood sugar) and skip words or switch words around in sentences, and have it a bit difficult with coordinating movement.

 

There are conflicting information as to whether it increases or decreases blood sugar, and whether it can cause low blood sugar.

I don't otherwise have diabetes, I am only interested in the mitochondrial improvements.

[thedevinroy]

It has an insulin promoting effect, so it moves your extracellular sugar into your cell to be used for energy. As to what that does for you depends on how much sugar your cells need. I believe that even though it leaves your system fairly quickly, the effects build over time. Your body has to get used to processing sugar more quickly, and once it does, your effects from it will change.

You should really cycle off a month every three months to avoid long lasting changes. Also, double up on your B Vitamins.

In my experience, I still notice a lift from it, but I also get a crash, too. Over time, the crashes get further and further apart and the lift gets lesser and lesser. This is my third cycle on this product, and I can tell you that the first few days are hell - can't sleep.

It helps with migraines and preventing zombie mode, but the super energetic boost you get from it dies off. I use it for weight loss. Doubles the effects from dieting in my experience. Turns what little blood sugar I have into usable energy. However the noticeable effect is that a crash is clearer. I would argue that without it, you would be experiencing a crash more spread out, less noticeable, but no less real. It's like it makes your body honest with you so that when it happens, you have three choices, fight through it and promote SIRT1, cave in and eat something, or take another pill to use the rest of your blood sugar up. When it creeps up on you, you might not know you have those choices at all, and before you know it, zombie mode has taken over.

Edited by devinthayer, 19 June 2016 - 05:27 PM.

[PeaceAndProsperity]

It has an insulin promoting effect, so it moves your extracellular sugar into your cell to be used for energy. 

Why do you think it is that I feel hungry when taking it, but as soon as I eat my situation is worsened. I feel "spaced out," dizzy, slightly fatigued and weak, and slightly irritable, as if I haven't eaten,

Would this suggest high blood sugar?

[thedevinroy]

It has an insulin promoting effect, so it moves your extracellular sugar into your cell to be used for energy.

Why do you think it is that I feel hungry when taking it, but as soon as I eat my situation is worsened. I feel "spaced out," dizzy, slightly fatigued and weak, and slightly irritable, as if I haven't eaten,
Would this suggest high blood sugar?

Not really. Intracellular glucose is quickly metabolized into pyruvate via glycolysis but also turned into glycogen. Therefore, it's both hypo and hyperglycemia - you have low blood sugar but high glycogen and pyruvate. Your body isn't used to running that optimally, so it takes time to adjust.

Working out and calorie restriction turns glycogen back into glucose. Glycogen phosphorylase is the enzyme responsible for that conversion. It needs vitamin b6 in order to work and increases its capacity by 25% in the presence of AMP. ATP is converted to AMP during exercise. AMP can also be produced from cAMP, and this is to my knowledge not a well studied function of PDE and glycogen depletion... Although the studies support PDE inhibition as having a greater glycogen reducing effect, especially glucagon.

Funny, supplementation with ALA typically decreases appetite thought to be via AMPK inhibition.

So what you have is most likely a need for more glucagon. Glucagon is raised when blood sugar is low, so to get used to ALA, it makes the most sense to be on a low carb diet. Glucagon is also raised during exercise, which might also help you get used to the effects.

Lastly, although this is obscure, an increase in pyruvate can lead to an increase in lactic acid. Malic acid and carnitine are the best ways of using up that pyruvate and converting it into energy instead. Water and light exercise (cooling down) are the best way to clean up lactic acid build up once it has accumulated. Not much talk about brain levels of lactic acid, other than their indication in aging. It is my belief that much of mental fatigue can be explained in the view of ph levels in the brain. In addition to malic acid, vinegar is known to lower blood PH levels.

Alpha Lipoic Acid is a chelator, so make sure you are eating plenty of minerals to replenish the lost iron, selenium, and zinc.

[thedevinroy]

https://en.m.wikiped...ki/Ketoacidosis

I was wondering why my kidneys liked me so much recently... I just figured ALA dissolved crystals. Didn't realize it prevented ketoacidosis.


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[gamesguru]

my kidneys liked me... it prevented ketoacidosis.

 

this promising flavonoid also has GDNF-stimulating and metabolic syndrome-ameleorating^[1] properties.

Grapefruit Derived Flavonoid Naringin Improves Ketoacidosis and Lipid Peroxidation in Type 1 Diabetes Rat Model.
Murunga AN1, Miruka DO1, Driver C1, Nkomo FS1, Cobongela SZ1, Owira PM1. (2016)

BACKGROUND:
Hypoglycemic effects of grapefruit juice are well known but the effects of naringin, its main flavonoid on glucose intolerance and metabolic complications in type 1 diabetes are not known.
OBJECTIVES:
To investigate the effects of naringin on glucose intolerance, oxidative stress and ketonemia in type 1 diabetic rats.
METHODS:
Sprague-Dawley rats divided into 5 groups (n = 7) were orally treated daily with 3.0 ml/kg body weight (BW)/day of distilled water (group 1) or 50 mg/kg BW of naringin (groups 2 and 4, respectively). Groups 3, 4 and 5 were given a single intra-peritoneal injection of 60 mg/kg BW of streptozotocin to induce diabetes. Group 3 was further treated with subcutaneous insulin (4.0 IU/kg BW) twice daily, respectively.
RESULTS:
Stretozotocin (STZ) only-treated groups exhibited hyperglycemia, polydipsia, polyuria, weight loss, glucose intolerance, low fasting plasma insulin and reduced hepatic glycogen content compared to the control group. Furthermore they had significantly elevated Malondialdehyde (MDA), acetoacetate, β-hydroxybutyrate, anion gap and significantly reduced blood pH and plasma bicarbonate compared to the control group. Naringin treatment significantly improved Fasting Plasma Insulin (FPI), hepatic glycogen content, malondialdehyde, β-hydroxybutyrate, acetoacetate, bicarbonate, blood pH and anion gap but not Fasting Blood Glucose (FBG) compared to the STZ only-treated group.

Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of Parkinson's disease.
Leem E1, Nam JH2, Jeon MT1, Shin WH3, Won SY4, Park SJ5, Choi MS6, Jin BK2, Jung UJ6, Kim SR7. (2014)

This study investigated the effect of naringin, a major flavonoid in grapefruit and citrus fruits, on the degeneration of the nigrostriatal dopaminergic (DA) projection in a neurotoxin model of Parkinson's disease (PD) in vivo and the potential underlying mechanisms focusing on the induction of glia-derived neurotrophic factor (GDNF), well known as an important neurotrophic factor involved in the survival of adult DA neurons. 1-Methyl-4-phenylpyridinium (MPP(+)) was unilaterally injected into the medial forebrain bundle of rat brains for a neurotoxin model of PD in the presence or absence of naringin by daily intraperitoneal injection. To ascertain whether naringin-induced GDNF contributes to neuroprotection, we further investigated the effects of intranigral injection of neutralizing antibodies against GDNF in the MPP(+) rat model of PD. Our observations demonstrate that naringin could increase the level of GDNF in DA neurons, contributing to neuroprotection in the MPP(+) rat model of PD, with activation of mammalian target of rapamycin complex 1. Moreover, naringin could attenuate the level of tumor necrosis factor-α in microglia increased by MPP(+)-induced neurotoxicity in the substantia nigra. These results indicate that naringin could impart to DA neurons the important ability to produce GDNF as a therapeutic agent against PD with anti-inflammatory effects, suggesting that naringin is a beneficial natural product for the prevention of DA degeneration in the adult brain.

 

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Edited by gamesguru, 19 June 2016 - 11:57 PM.

[normalizing]

ala is a damn tough asshole to deal with, and if you really dont have any conditions like say diabetes or so on, stay away from it. i used it for hangovers, it energized me when i was down but it was so infrequent and disruptive long term and the expensive r version DOESNT WORK for me and probably for most and reason being so expensive is because its trademarked and distributed solely by a specific company duh

 

the grapefruit studies, you will probably need a basket of those to get good amount of naringin, so good luck with that. also, isnt it concentrated in the peel anyway? maybe eat a basket of grapefruit peels.

[gamesguru]

agreed ala is good for diabetes and maybebterminal dementia but not much else, cos of (in my case) terrible heartburn.

the juice of grapefruit contains a good amount of naringin, and maybe if it's organic, you could eat the pulp and some peel.

"Juice was prepared from the fresh fruit via different methods (by hand, squeezer or blender). The naringin content, after hand-squeeze, ranged from 115 to 384 mg/l."

[PeaceAndProsperity]

ala is a damn tough asshole to deal with, and if you really dont have any conditions like say diabetes or so on, stay away from it. i used it for hangovers, it energized me when i was down but it was so infrequent and disruptive long term and the expensive r version DOESNT WORK for me and probably for most and reason being so expensive is because its trademarked and distributed solely by a specific company duh

I am interested in mitochondrial biogenesis. Already taking loads of alcar, but alcar+ala is superior than any of them alone. If only there was something that could better increase mitochondrial biogenesis without the annoying side-effects of ala.

[gamesguru]

i would spread 2g ALCAR with less than 300mg ALA (read 100mg). other things can induce a greater degree of mitochondrial biogenesis, such as exercise[2] or green tea [1]. and generally, a high antioxidant diet is as effective as mega-dose ALA in reducing ALCAR oxidation.

[PeaceAndProsperity]

i would spread 2g ALCAR with less than 300mg ALA (read 100mg). other things can induce a greater degree of mitochondrial biogenesis, such as exercise[2] or green tea [1]. and generally, a high antioxidant diet is as effective as mega-dose ALA in reducing ALCAR oxidation.

Like alcar + resveratrol?

[normalizing]

agreed ala is good for diabetes and maybebterminal dementia but not much else, cos of (in my case) terrible heartburn.

the juice of grapefruit contains a good amount of naringin, and maybe if it's organic, you could eat the pulp and some peel.

"Juice was prepared from the fresh fruit via different methods (by hand, squeezer or blender). The naringin content, after hand-squeeze, ranged from 115 to 384 mg/l."

 

wow thats quite the naringin from just juice. i read it long time ago and maybe i didnt pay much attention but naringin was extracted in a specific way from the peels only and in high amounts too

[gamesguru]

i think the reason its extracted mostly from peels has to do with the fact that nobody wants the peels or cannery waste, so they get turned into things like d-limonene, naringin, and hesperidine. fresh red grapefruit flesh has 32.64mg/100g Naringenin. maybe the peel has 2-3x the quantity as the juice, nothing too significant.

 

strong derail is strong. sorry guys.

 

Like alcar + resveratrol?

sure, i don't see any problem with that. should even work better than ALA, but i said high antioxidant diet.

Edited by gamesguru, 20 June 2016 - 03:47 PM.

[thedevinroy]

Speaking of high antioxidant diets, IIRC, cancer patients should fill 1/2 their plate with veggies. I heard it on a podcast, so it must be true.


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[thedevinroy]

I wonder if that company that makes ALA also did the study theorizing stabilized membrane permeability from adding ALA when ALCAR supplementation was increased. Makes sense in theory... I think they even gave a ratio.

Yeah GERD sucks on ALA. If I don't have enough water or food to wash it down, I can feel it so bad, I see the ulcer forming in my mind's eye.

And you guys forgot to mention its marginal benefits in weight loss! Think if you combined it with other marginally effective weight loss supplements like chromium and green tea and caffeine and cocoa. You'd still be fat, but at least you'll be spending enough on your health over time to frustrate yourself into dieting and exercising more.


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[thedevinroy]

Back to the original topic...

http://www.alzdiscov...lity/report/ala

I think we all need to understand the place of reactive oxygen species and its effect on our ability to grow. Anything reducing stress and specifically oxidative stress has the ability to also decrease our body's ability to grow from these natural stressors of life. Think about it this way, if you never worried or were challenged, you would never have reason to do anything differently. Your cells are the same way, so if you coddle the mitochondria to the point where they are barely being challenged, they will get bored and unproductive (or in other words, sedentary), in a personified manner of speaking.

Studies with ALA alone do terribly. Studies with ALA and a pro-oxidant do better. Fish Oil being an obvious choice. Ketone bodies from fat breakdown are pretty oxidative.

The opposite is also true. Too much oxidation causes damage that is irreparable. Every organism has its sweet spot. Humans haven't really discovered it yet, but I am thinking that ALA and Co-Q10 are going to help us find it.

Edited by devinthayer, 20 June 2016 - 09:37 PM.

[gamesguru]

coddle the mitochondria

[thedevinroy]

https://en.m.wikiped...lyl_isomerase_D

This protein assists in cell death from Reactive oxygen species (mitochondrial premiability increase via MPT) which is thought to be fatal to the cell.

Reduced oxygen or ATP can also lead to necrosis, which is far worse than apoptosis. I'd rather live a stimulating life than a safe and dull one.

http://www.diffen.co...sis_vs_Necrosis

http://www.ncbi.nlm....pubmed/9157970/

Currently researching articles on antioxidants causing necrosis in healthy cells...



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[normalizing]

well as i said, regular ala seems to help with hangovers not sure how this works but it does somehow and beyond that nothing really

[gamesguru]

hangovers and diabetes, two things you otherwise cant control

[Junk Master]

FYI you can find tons of Naringin supplements and it has been used extensively by the bodybuilding community for years.

 

Swanson's carries an extract.  NOW sells one.

 

 

[PeaceAndProsperity]

Lipoic acid is often used in conjunction with vitamin C therapy, because it helps its utilization (or so I think), so that's another use for it

[normalizing]

FYI you can find tons of Naringin supplements and it has been used extensively by the bodybuilding community for years.

 

Swanson's carries an extract.  NOW sells one.

 

why do they take it? i havent found anything regarding muscle mass etc.

[Junk Master]

They use it to enhance the half-life of the ephedrine/caffeine or ephedrine/caffeine/Aspirin stack used for fat burning.

 

It is an incredibly effective stack if you can tolerate the side effects, which include high blood pressure, shakiness, nausea.  I could never use it any lift heavy weights without just feeling terrible.

 

Now Fen-Phen worked like a charm!

 

BTW Naringin definitely does extend the effects of caffeine.  I'd just leave out the ephedrine!

 

There are many articles about grapefruit juice and it's ability to increase oral bioavailability of certain drugs.  If you are interested, here's one--

 

http://www.ncbi.nlm....les/PMC1873672/

[gamesguru]

Currently researching articles on antioxidants causing necrosis in healthy cells...

did you come up empty handed?

 

why do they take it? i havent found anything regarding muscle mass etc.

 

probably they were influenced by this 1996 study. it explains how non-naringin grapefruit components contribute the bulk of testosterone promoting effects, which the bodybuildingforums however failed to notice. the study also explains how oranges can provide a very similar effect on the liver (despite considerably less naringin, which is what's important for us GDNF junkies):

The effect of various citrus juices and solutions of naringin on CYP3A activity in rat liver microsomes was compared by measuring the formation of 6 beta-hydroxytestosterone from testosterone. Control enzyme activity was reduced by more than 70% by grapefruit juice. Freshly-squeezed sour (Seville) orange juice containing 20% as much naringin was comparable to grapefruit juice in its ability to inhibit microsomal activity. An aqueous solution of naringin at the same concentration as in grapefruit juice produced only a small decrease in 6 beta-hydroxytestosterone formation. Dilution of grapefruit juice with a naringin solution reduced the inhibitory activity of the juice even though naringin concentration did not change. Naringenin did not form under the incubation conditions used indicating that it did not contribute to the inhibition produced by grapefruit juice. Finally, organic extracts of grapefruit juice possessed considerable inhibitory activity even though naringin was not extractable.

 

it also has other potential benefits on the muscle health, and of the motor neurons (see below two quotes: at least I could find research on developing neurons, in baby rats haha). i'm also starting to see it as a challenger to 9-methyl-β-carboline in terms of dopaminergic regeneration. all of that research on GDNF and dopamine is fairly recent, 2014. although it all seems to be "protection" not regeneration, but neurotrophin literally means genesis of the nervous, and what is GDNF? but we need a few more years for the research to really answer the questions. til then draw your own conclusions, while i recommend everyone give grapefruit a shot.

you might say, 'that's amazing, no way grapefruit can do all that.' how would you know!? all you do is watch them collect dust at Kroger all week, and then you walk past the employee throwing out the mouldy ones without even acknowledging you are within arm's reach of grapefruit. nobody eats those on the daily, not Dr. Oz nor did Marilyn Monroe.  meanwhile, everybody who's anybody is gorging themselves on the pink succulence. just food for a thought. watch out for drug interactions!!

Recent investigations also suggested that the hypoglycemic activity of naringin is mediated via uptake of glucose in the skeletal muscle (84). Maximum stimulation was seen with 75 μmol/L naringenin for 2 h, which was comparable to maximum insulin response in L6 myotubes (84). Increased glucose uptake is mediated via upregulation of AMPK in skeletal muscle cells (84). AMPK-activated improvement in metabolic syndrome was also reported by Pu et al. (60). In this study, naringin supplementation (0.2 g/kg of diet) improved glucose intolerance and insulin resistance in a model of high-fat-diet–fed mice (60).

 

Glial cell-line derived neurotrophic factor (GDNF) is a potent survival factor for motor neurons. Previous studies have shown that some motor neurons depend upon GDNF during development but this GDNF-dependent motor neuron subpopulation has not been characterized. We examined GDNF expression patterns in muscle and the impact of altered GDNF expression on the development of subtypes of motor neurons. In GDNF hemizygous mice, motor neuron innervation to muscle spindle stretch receptors (fusimotor neuron innervation) was decreased, whereas in transgenic mice that overexpress GDNF in muscle, fusimotor innervation to muscle spindles was increased. Facial motor neurons, which do not contain fusimotor neurons, were not changed in number when GDNF was over expressed by facial muscles during their development. Taken together, these data indicate that fusimotor neurons depend upon GDNF for survival during development.

 

Naringin improves zidovudine- and stavudine-induced skeletal muscle complications in rats.
Adebiyi OO1, Adebiyi OA2, Owira P1. (2016)

Chronic use of nucleoside reverse transcriptase inhibitors (NRTIs) in managing human immunodeficiency virus (HIV) infection has been associated with several complications. Available management options for these complications have yielded controversial results, thus the need to urgently find newer alternatives. Naringin, a plant-derived flavonoid, has been shown to possess antioxidant and antiapoptotic properties which can be exploited in managing NRTI-induced complications. This study therefore investigated the effects of naringin on some NRTI-induced complications. Forty-nine rats (200-250 g) were divided into seven groups and were orally treated with stavudine (d4T)-only, d4T + naringin, d4T + vitamin E, zidovudine (AZT)-only, AZT + naringin, AZT + vitamin E, and distilled water, respectively. Drugs were administered once daily for 56 days, and oral glucose tolerance tests conducted on day 54 of the experiments and rats were thereafter sacrificed on day 56 by halothane overdose. Plasma samples and the left gastrocnemius muscles were stored at -80°C for further analysis. There was significant glucose intolerance, insulin resistance, oxidative stress, and apoptosis in the skeletal muscles of AZT- or d4T-only-treated rats. Naringin, however, significantly reduced fasting blood glucose and fasting plasma insulin concentrations, mitigated glucose intolerance, and insulin resistance in addition to reducing malondialdehyde and carbonyl protein concentrations when coadministered with either NRTIs. Furthermore, naringin improved antioxidant enzyme activities, reduced skeletal muscle BCL-2-associated X protein expression, and improved B-cell lymphoma-2 protein expression compared to AZT- or d4T-only-treated rats. Naringin ameliorated AZT- and d4T-induced complications and therefore should be further investigated as a possible nutritional supplement in managing HIV infection.

Naringin: A Protector of the Nigrostriatal Dopaminergic Projection
Un Ju Jung,1 Eunju Leem,2,3 and Sang Ryong Kim (2014)

Parkinson's disease is the second most common neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons and a biochemical reduction of striatal dopamine levels. Despite the lack of fully understanding of the etiology of Parkinson's disease, accumulating evidences suggest that Parkinson's disease may be caused by the insufficient support of neurotrophic factors, and by microglial activation, resident immune cells in the brain. Naringin, a major flavonone glycoside in grapefruits and citrus fruits, is considered as a protective agent against neurodegenerative diseases because it can induce not only anti-oxidant effects but also neuroprotective effects by the activation of anti-apoptotic pathways and the induction of neurotrophic factors such as brain-derived neurotrophic factor and vascular endothelial growth factor. We have recently reported that naringin has neuroprotective effects in a neurotoxin model of Parkinson's disease. Our observations show that intraperitoneal injection of naringin induces increases in glial cell line-derived neurotrophic factor expression and mammalian target of rapamycin complex 1 activity in dopaminergic neurons of rat brains with anti-inflammatory effects. Moreover, the production of glial cell line-derived neurotrophic factor by naringin treatment contributes to the protection of the nigrostriatal dopaminergic projection in a neurotoxin model of Parkinson's disease. Although the effects of naringin on the nigrostriatal dopaminergic system in human brains are largely unknown, these results suggest that naringin may be a beneficial natural product for the prevention of dopaminergic degeneration in the adult brain.

Effects of naringin, a flavanone glycoside in grapefruits and citrus fruits, on the nigrostriatal dopaminergic projection in the adult brain
Un Ju Jung1 and Sang Ryong Kim, Ph.D (2014)

Recently, we have demonstrated the ability of naringin, a well-known flavanone glycoside of grapefruits and citrus fruits, to prevent neurodegeneration in a neurotoxin model of Parkinson's disease. Intraperitoneal injection of naringin protected the nigrostriatal dopaminergic projection by increasing glial cell line-derived neurotrophic factor expression and decreasing the level of tumor necrosis factor-alpha in dopaminergic neurons and microglia, respectively. These results suggest that naringin can impart to the adult dopaminergic neurons the ability to produce glial cell line-derived neurotrophic factor against Parkinson's disease with anti-inflammatory effects. Based on these results, we would like to describe an important perspective on its possibility as a therapeutic agent for Parkinson's disease.

Naringin protects the nigrostriatal dopaminergic projection through induction of GDNF in a neurotoxin model of Parkinson's disease.
Leem E1, Nam JH2, Jeon MT1, Shin WH3, Won SY4, Park SJ5, Choi MS6, Jin BK2, Jung UJ6, Kim SR7. (2014)

This study investigated the effect of naringin, a major flavonoid in grapefruit and citrus fruits, on the degeneration of the nigrostriatal dopaminergic (DA) projection in a neurotoxin model of Parkinson's disease (PD) in vivo and the potential underlying mechanisms focusing on the induction of glia-derived neurotrophic factor (GDNF), well known as an important neurotrophic factor involved in the survival of adult DA neurons. 1-Methyl-4-phenylpyridinium (MPP(+)) was unilaterally injected into the medial forebrain bundle of rat brains for a neurotoxin model of PD in the presence or absence of naringin by daily intraperitoneal injection. To ascertain whether naringin-induced GDNF contributes to neuroprotection, we further investigated the effects of intranigral injection of neutralizing antibodies against GDNF in the MPP(+) rat model of PD. Our observations demonstrate that naringin could increase the level of GDNF in DA neurons, contributing to neuroprotection in the MPP(+) rat model of PD, with activation of mammalian target of rapamycin complex 1. Moreover, naringin could attenuate the level of tumor necrosis factor-α in microglia increased by MPP(+)-induced neurotoxicity in the substantia nigra. These results indicate that naringin could impart to DA neurons the important ability to produce GDNF as a therapeutic agent against PD with anti-inflammatory effects, suggesting that naringin is a beneficial natural product for the prevention of DA degeneration in the adult brain.