Magnolia grandiflora leaf - anonaine and related alkaloids as 5-HT1A ligands/DAT inhibitors

[Alchemica]

Bought myself a new ally, a Magnolia grandiflora tree.

 

 

The flower contains liriodenine, anonaine, dehydroremerine (0.52% total alkaloids)

Leaf from the flowering plant contains anonaine, remerine, liriodenine and rutine (0.54 % total alkaloids) It also contains essential oils 0.58 %

 

 

Anonaine, the principle leaf alkaloid displayed affinity of 0.8 µM, the same order as the reference compounds nomifensine (0.2 µM), but more potent than amineptine and dexamphetamine at DAT. The oxoaporphine liriodenine was virtually devoid of activity as a dopamine reuptake inhibitor. It also has affinity for 5-HT1A and α1 adrenergic receptor affinity. Although not overly potent, studies suggest they are α1A antagonists, as is demonstrated by the vasorelaxant responses.

The flowers are edible and said to have an exquisite flavour and are used as a spice and condiment. My flowers were dried and aged on the plant so lost most of that but still interesting flavours. Volatile constituents are mainly monoterpenoids and sesquiterpenoids. Look forward to a tea from the fresh flowers.

Interestingly, the crude extract of the seeds contains 10% 4-O-methylhonokiol. It is also found in the bark. This is a potent CB2 receptor ligand which readily crosses the blood brain barrier and attenuates memory impairment.

In addition to anonaine, liriodenine etc, the leaves contain sesquiterpene lactones like parthenolide which has intriguing activity but low bioactivity.

 

Please be aware that the toxicity of the leaf material is unestablished while the constituents are more characterised.

Well the Magnolia flower tea was interesting tastewise maybe a slight subjective uplift. Something spiritual to it but I wanted more DAT/5-HT1A action. Chewed through a whole flower as tea.

 

Wanted to develop a bit of a relationship with this plant, see if it could be a good functional motivational aid, so I tried 2 tsp dried leaf material on top. Struggling to find info on doses but the same alkaloids at 5-10mg/kg in mice exhibited antidepressant activity. For me, the upper alkaloid dose would be about 80mg alkaloids in human equivalent doses.

 

Interesting resonance, seems somewhat useful for doing things. Soft energetic resonance, seems superior to lotus/lily. Not really stimulatory but functional it seems.

3 tsp of crushed dried leaf: need all the uplift I can get. There's something but it's not pushy stimulant wise, feels clean, a focusing energy but soft.

Started another day with leaves 17g dried, ~ 90mg alkaloids. I had to have an early sleep on it, it seems to have some waves of calming sedation for me anyway. Then it picked up into something more 'wanna do stuff'.

Followed that up the next day with 17g and I had quite a good day. I tend to find stimulants calming and de-scattering so results may vary.

I do like the magnolia leaf at decent doses but I'm going to leave my experiments there, let my ally grow before I find it too useful. Wouldn't say it's going to make a magnolia crack but still interesting. If I find a large M. grandiflora, I might make magnolia leaf extract, the tea is quite unpleasant and it would be nice to have a concentrated extract.

Anyone done any trials themselves?

Edited October 23, 2017 by Alchemica

[Zedo]

I had no idea this plant had any use. As we are slowly deciding what to plant in our garden I always see them everywhere and go... hmm nah I want something useful. Silly me. Me thinks me am getting one this weekend to fill a spot I have saved for a flowering tree. 

 

Are they all the same or are there different types of Magnolia grandiflora?

 

gonna have to do some reading tonight.

[HolographicYou]

I work in a wholesale tree nursery and these magnolias go out by the truck load.

Lots of pretty cultivars available:

'Kay parris'

'Little gem'

'Coolwyn gloss'

'Exmouth'

And the more desired 'Teddy bear' for its large round leaves.

Very aesthetic looking trees.

 

Next time we prune I might bring the trailer in. 

[Zedo]

Does it matter what type of magnolia grandiflora? Or are they all safe and useful to use?

[DualWieldRake]

On 10/24/2017 at 8:21 AM, Zedo said:

I had no idea this plant had any use. As we are slowly deciding what to plant in our garden I always see them everywhere and go... hmm nah I want something useful. Silly me. Me thinks me am getting one this weekend to fill a spot I have saved for a flowering tree. 

 

Are they all the same or are there different types of Magnolia grandiflora?

 

gonna have to do some reading tonight.

 

How is a plant that adds a nice fragrance to your garden not usefull.

Profile of volatiles (and alkaloids) can differ between specimens of the same species, so sow a bunch or use for example a nose to pick one that you like

Edited October 29, 2017 by DualWieldRake

[Inyan]

I love Magnolias and always have. Right now, I have perhaps a few hundred seeds soaking in the refrigerator for spring planting.

[Zedo]

On 30/10/2017 at 9:56 AM, DualWieldRake said:

 

How is a plant that adds a nice fragrance to your garden not usefull.

Haha the obvious is blind in plain sight lol.

 

The bees would love it I imagine. And they make this wicked stuff that you breathe to stay alive lol. 

[Alchemica]

This morning, my shamanic mug contains my morning anthocyanins and phenolics (Hibiscus) and an alkaloid source (Magnolia leaf)

 

While I did some work with Magnolia leaf when my mood was super poor, I wanted to try a lower dose with my Hibiscus (which has antidepressant and mild anxiolytic effects itself).
 

The leaf has strong antioxidant/reducing capacity - the antioxidant activity of Magnolia officinalis leaf (can't find data for M. grandiflora) was related to its main chemical compositions including flavonoids, phenolics and lignanoids. It also contains parthenolide. Please note, this is still an area of research, we have more to learn.
 

10g Magnolia leaf [Leaf from the flowering plant contains anonaine, remerine, liriodenine and rutine (0.54 % total alkaloids) It also contains essential oils 0.58 %], which may be around 50mg of anonaine [5-HT1A/DAT activity, along with α1 adrenergic receptor affinity and antitumour, vasorelaxation, antioxidative, antiparasitic and antimicrobial effects] and related alkaloids going by my 6am math which is questionable. This is at the lower active dose level human dose equivalence to what showed antidepressant efficacy in animal models.

 

The only thing is the taste... it's really quite a challenge.

Subjective verdict on this morning's healing brew. If you want a pushy anxiogenic morning perk, go with coffee. The mood uplift of the Hibiscus flower and Magnolia leaf seems pleasant and acuteishly there. Went for a nice walk. It wasn't pushy just more refreshing. These alkaloids seem to lack the noradrenergic push, they feel pleasant but soft. I went for a longer than normal walk but it was just pleasantly cruisy. I haven't really explored new areas since Milly passed, kind of been locked in to typical walks where I go on a mission to do things. Today I felt more like going for a bit of an adventure, checking out new things but stopping to smell the roses at the same time. Just a mild, nice, gentle uplift and clean pleasantness so far. Nothing unpleasant, apart from the taste of the leaf.

[Alchemica]

I should note my experiments have been with dried leaf from my Magnolia grandiflora "Little Gem"

@Zedo That's what I'm trying to ascertain, is the differences between gradifloras at the moment

 

Trying to improve the taste of Magnolia leaf tea and check differences between smaller variants and the big trees, gathered a couple of leaves off the ground from a large Magnolia.

 

Leaves average 1.6g each dry. They have the same characteristic smell as my Magnolia grandiflora "Little Gem" but they are a little more palatable from a quick sip, ever so slightly. Not sure if it's just some curing that's gone on in leaves maturing and falling off the tree, or loss of some essential oils.

 

@10g (lower potentially active doses of anonaine and related alks as an antidepressive DAT inhibitor/5-HT1A agonist), it's once again subjectively pleasant but mild, gently uplifting. A subtlety to interact with. My morning walk was once again a bit different, enjoyable, more ability to remain somewhat more goal-oriented potentially.

Edited March 4, 2018 by Alchemica

[Alchemica]

@Supplemental 10g Magnolia grandiflora leaf. Just to see where it went, rather than craving more. Had a nice day with some potentially increased pro-sociality noted on the 10g, got out to a peaceful Japanese Garden.

 

The utilisation of a dual DAT inhibitor/5-HT1A agonist such as the alkaloids in Magnolia grandiflora intrigues me a lot.

 

Effective low abuse potential dopaminergics that may increase frontal cortical dopamine and gently modulate the reward system are sorely needed in medicine for treating everything from ADHD, to severe anhedonic depressions, to attenuating as an augmentation strategy, cognitive issues and negative symptoms in psychotic disorders etc.

 

The dual action profile is intriguing as:

 

1) 5-HT1A agonism may reduce potential sensitisation and the development of tolerance to pro-cognitive effects - It is suggested that the sensitisation development to dopamine reuptake inhibitors may be opposed by buspirone co-administration due to the reduction in the sensitivity of 5-HT1A somatodendritic receptors. Attenuation of methylphenidate-induced tolerance on cognition is also seen with the co-administration of a 5-HT1A active compounds

 

2) 5-HT1A agonists are often pro-cognitive and often pro-social, along with being anxiolytic. Can't be overly simplistic, it's rather dependent on how the agonist is acting, pre-synaptically and post-synaptically.There is generally an increase in dopamine release in prefrontal cortex mediated by the direct or indirect activation of the 5-HT1A receptor

 

Add the antitumour, vasorelaxation, antioxidative, antiparasitic and antimicrobial effects of these alkaloids... then there's the healing benefits of the polyphenols if you use leaf material.

 

Coffee has more subjective stimulation and abuse potential, in an unpleasant way. This is nice as a potential antidepressive, clean, pro-cognitive, seemingly low abuse plant medicine. If I had to describe it, I'd call it a "Shen tonic". It's feels like a subtle uplift of spirits, over a nasty push. It's seemingly got a pro-social edge and a certain emotional and transcendent element to it IMO.

"(−)-anonaine has good selectivity for 3H-dopamine uptake. The affinity of (−)-anonaine at dopamine D1 3H-SCH 23390 and D2 3H-raclopride binding sites was low [19]. (−)-Anonaine displays dopamine uptake inhibitory properties. 5-HT1A receptor plays an important role in depressive disorders. One study has shown that 1,2-dimethoxy-5,6,6a,7-tetrahydro-4H-dibenzoquinoline-
3,8,9,10-tetraol, (−)-anonaine, liriodenine, and nornuciferine are the main constituents of the aerial parts of Annona cherimola [2]. These main constituents produced antidepression-like effects due to the 5-HT1A receptor agonistic activity of (−)-anonaine and nornuciferine [2]. These results indicate that (−)-anonaine displays dopamine uptake inhibitory and 5-HT1A agonistic activity with anti-depressant activity." [1]

 

Edited March 6, 2018 by Alchemica

[Alchemica]

@10g Magnolia grandiflora leaf twice in a day, mood uplift became quite good. Cognitively and emotionally, even spiritually nice.

 

I've mentioned one dominant alkaloid constituent, (-)-anonaine. As I've said, this has good selectivity as a dopamine reuptake inhibitor and at 5-HT1A with some α1-adrenoceptor antagonist activity. Through both dopamine reuptake inhibition and 5-HT1A agonism (5-HT1A receptor stimulation increases dopamine release in frontal regions of the brain), the net dopaminergic effect is seemingly pleasant. α1-adrenoceptor antagonists may also enhance brain functions. Such antagonists enhanced memory function by activating NMDA receptor-mediated ion currents in the hippocampus

 

Another constituent is remerine/roemerine. These were found to be quite decent antagonists at 5-HT2A and 5-HT2C receptors and α1 receptors. The 5-HT2A/C antagonism occurs with good selectivity over activity at 5-HT2B, α1A, α1B and α1D receptors. This antagonism likely functions to increase cortical dopamine and augments the therapeutic potential of some dopamine reuptake inhibitors.

 

Liriodenine stimulates respiration in animals and has a short lasting hypotensive effect. It was shown to have activity against gram-positive bacteria, acid-fast bacteria, and several fungal organisms with relatively low acute toxicity and relatively potent anti-cancer effects. It was found to be a muscarinic receptor antagonist. In combination with anonaine etc, it displayed anti-depressant effects

 

[Alchemica]

I've been re-exploring this in my research lately. All in all, even I'm now hesitant to explore this one personally due to odd effects longer-term on lowering dopamine and the fact that it has not been widely used/marketed by others suggests there may be need for caution

 

 

Exploring the Magnoliaceae.pdf

anonaine-final.pdf

 

I came to the conclusion:

 

Quote

Interestingly, despite relatively potent DAT inhibition, the longer-term net effect of (-)-anonaine on dopamine seems to be decreased dopamine content, potentially via interfering with dopamine biosynthesis via tyrosine hydroxylase [4]. This may be why, contrary to psychostimulant effects, the more traditional use of plants containing (-)-anonaine does not seem to reflect those expected in the case of more typical dopamine transporter inhibition. 

Also, caution is required as some studies have noted potential neurotoxicity from Annonaceae extracts [5] with some reports of atypical parkinsonism being noted. That said, while methanol extracts have displayed toxicity, hexane extracts were devoid of such, so it may not be the anonaine and related alkaloids responsible for neurotoxicity, instead it is possible Annonaceous acetogenins may be responsible.

Nonetheless, psychostimulant activity seems to be lacking in anonaine containing plants:

                  Several species of Annona (Annonaceae) are used in traditional Mexican medicine due to their anti-anxiety, anticonvulsant, and tranquilizing properties

 

 

anonaine-final.pdf

Exploring the Magnoliaceae.pdf

Edited May 27, 2023 by Alchemica