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Alchemica

Rapid acting antidepressant plants - Gardenia jasminoides, Polygala tenuifolia, Saffron. Dihydromyricetin

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Apart from 5-HT2A agonists, Aya and scopolamine what else is there?

800px-Gardenia_jasminoides_cultivar_magn


Bought some seeds to grow of this one...

 

Gardenia jasminoides possess multiple biological activities, such as antioxidant properties, hypoglycemic effect, inhibition of inflammation, antidepressive activity, and improved sleeping quality. A number of chemical components of G. jasminoides have been isolated and characterized, including iridoids, iridoid glucosides, triterpenoids, organic acids, and volatile compounds. Geniposide, genipin, gardenoside, crocin, and iridiod are the major bioactive compounds found in G. jasminoides. For instance, the yield of geniposide reached 10.9% under certain extraction conditions [1]

Gardenia jasminoides showed a significant rapid acting antidepressant effect [2]. The antidepressant response started at 2 hours after administration - similar to ketamine, it may have a great clinical potential for treating patients with depression [3]. It's used in Yueju pill, a traditional Chinese medicine formulated to treat syndromes of mood disorders. Yueju has been shown to promote a fast-onset antidepressant effect clinically and in preclinical studies.  An extract had the functions of learning and memory improvement and the neuroprotection [4] Alongside this neuroprotective effect, geniposide enhanced cholinergic neurotransmission, which likely contributes to its memory enhancing effect [5].

Gardenia yellow pigment (GYP) is a collection of compounds with shared structure of crocin, which confers antidepressant activity. These compounds are remarkably enriched in Gardenia jasminoides, implicated in rapid antidepressant effects that are exerted through enhanced neuroplasticity. Antidepressant response was detected at 30 min, and lasted for at least 3 days post a single administration of GYP [6]

 

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There's an affordable 10:1 polygala root extract in Aus now. I tried the plain root but found it too mild, an extract might be interesting.
 

"Root of Polygala tenuifolia (Radix polygalae) is a traditional herb used for its tranquillizing and anti-amnesic effects in East Asian countries. Recent research disclosed wide range of biological activities of Radix polygalae and it active compounds, such as dopaminergic D2 and serotonergic 5-HT2 receptor binding, NMDA toxicity protection, prevent depression symptoms in chronic mild stress model animals, and induction of brain-induced neurotrophic factor (BDNF) in the hippocampus. Behavioral tests such as female urine sniffing test, novelty suppressed feeding, learned helplessness paradigm and anhedonia in chronic mild stress exposed animals require repeated dose of monoaminergic antidepressant reagents to exert antidepressant-like effects. But single or two doses of Radix polygalae extract improved depression related behaviors in these tests. Like ketamine, pretreatment of an AMPA receptor antagonist abolished the antidepressant-like effect of Radix polygalae. Also the phosphorylation of hippocampal AMPA receptor GluR1 subunit was changed.
 

Radix polygalae is a commonly prescribed reagent by practitioners of traditional medicine. According to these recent findings, Radix Polygalae extract may have rapid-onset antidepressant effect which can be a safer alternative to ketamine and lead to the development of life-saving medications by reducing the risk of suicide in emergency situations" [7]

 


There's also saffron

74959028def725582fe27881fcac4d04--saffro

 

The crocins are hydrophilic carotenoids that can act as antioxidants, improve learning and memory, be used for treatment of brain injury, mood disorders, OCD, joint pain and muscle dysfunction in osteoarthritis, metabolic syndrome and related mood disorders and neurodegenerative damage, and have a protective effect against brain damage

 

Aside from the NMDA affinity and sigma-1 binding, there is evidence that crocins act as reuptake inhibitors of dopamine and norepinephrine, while aside from it's GABAA affinity, safranal acts primarily on serotonin reuptake.

 

"The antioxidant properties of saffron derivatives may also be relevant. Mood disorders are associated with elevated oxidative stress and a deficit of exogenous antioxidants, affecting immune and inflammatory responses in a way, which may promote neurodegeneration (Leonard and Maes, 2012). There is good evidence that the antioxidants in saffron extracts protect against oxidative stress in the central nervous system (Mehri et al. 2015; Oruc et al. 2016), constituting a second potential mechanism of therapeutic action.

 

The most important indicator of the quality and commercial value of the saffron is its contents of crocin I and II, which are specified in trade standards. The Chinese Pharmacopoeia stipulates that the total content of crocin I and II should not be less than 10.0 %."
 

In an analysis of 63 saffrons, the crocin I content range was 6.6–23.7 %.


There is a TGA listed coated tablet containing either 11 mg or 14 mg of standardised saffron extract (affron), derived from the stigmas of Crocus sativus L. and standardised to contain >3.5% Lepticrosalides® (a measure of bioactive compounds present in saffron, including safranal and crocin. Two tablets daily constitutes a dose.

 

Saffron (Crocus sativus L.) has demonstrated antidepressant effects in clinical studies and extensive anxiolytic effects in experimental animal models. It reputedly has acute effects.
 

Safranal is an effective anticonvulsant in animal models, shown to act as an agonist at GABAA receptors. Saffron extracts and crocetin had a clear binding capacity at the PCP binding side of the NMDA receptor and at the sigma-1 receptor while crocins attenuated schizophrenia-like behavioural deficits. Crocin has been shown to be an antioxidant and neural protective agent
 

Saffron is a potential efficacious and tolerable treatment for major depressive disorder with anxious distress. [1] It increased mood, reduced anxiety and managed stress without side effects, offering a natural alternative to standard treatments [2] Saffron is as effective as fluvoxamine in the treatment of patients with mild to moderate OCD [3]

More on saffron here:

 

Edited by Alchemica
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Update.

Just as I propagate my Gardenias (one of my antidepressive babies below)

 

Genipin normalizes depression-like behavior induced by prenatal stress through inhibiting DNMT1.

Abstract

Synthetic antidepressants in current use for the complex etiopathogeneses of depression have slow response and remission as well as various unpleasant side effects. As a result, it is imperative to develop new antidepressants with more effectiveness and less severe side effects. Recent studies demonstrated that genipin, the aglycon of geniposide, extracted from Gardenia jasminoides Ellis has antidepressive effects. However, knowledge regarding the molecular mechanisms of its antidepressant effects remains limited. Employing a depression-like mouse model, we confirmed that genipin is capable of correcting depressions-like behaviors induced by prenatal stress in offspring from prenatally stressed dams (defined as PRS mice). In further experiments, we found that the effect of genipin on PRS mice occurs through DNA demethylation by inhibiting DNA methyltransferase 1 (DNMT1), normalizing the expression of reduced brain-derived neurotrophic factor (BDNF) in the hippocampus.

 

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Another great post. 

 

Common garden plant amazing potential. After your last mention of Gardenia jasminoides I picked one up from that big green warehouse as tubestock for ~$3

 

Just did a quick search on which part of the plant is used for GYP extraction,  and it seems to be the fruit. Interesting...  Because I don't think I've ever seen (or should I say, noticed) any fruit on a gardenia. Or is it just me? 

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I haven't noticed fruit either on mine but I haven't had it for long. I'm hoping the leaf is a viable, lower yield iridoid glycosides source for general antidepressant use. It makes a really pleasant tea.

The plant contains iridoid glycosidesgeniposide 56.03, genipin 1.72, gardenoside 2.16 and geniposidic acid 1.79 mg/g The stem and root contain oleanolic acid, D-mannitol and stigmasterol. The leaves contain an antifungal compound, cerbinal.

Geniposide and gardenoside contents in different G. jasminoides organs were also quantitatively determined; it was found that iridoid content was somewhat lower in the vegetative tissues than in the flowers and fruits.

Edited by Alchemica
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I've mentioned elsewhere but for the sake of a complete thread, this one is really cheap and available as a commercial extract in Aus. I had some for lunch.

The Moyeam grows in Zhangjiajie ethnic enclaves, and is considered to be the god's gift by the Tujia minority, best known as the "Tujia God tea".

 

There may be drug interactions

 

Moyeam's_plant.JPG

 

Here's a write up:

 

 

Dihydromyricetin exerts a rapid antidepressant-like effect in association with enhancement of BDNF expression and inhibition of neuroinflammation.

 

The present data indicate that DHM exerts a more rapid antidepressant-like effect than does a typical antidepressant, in association with enhancement of BDNF expression and inhibition of neuroinflammation.

 

Dihydromyricetin (DHM) is a kind of flavonoid natural product that has been reported to display multiple pharmacological effects. Dihydromyricetin has been demonstrated to show antioxidative, anti-inflammatory, anticancer, antimicrobial, cell death-mediating, and lipid and glucose metabolism-regulatory activities.

 

DHM exerts a more rapid antidepressant-like effect than does a typical antidepressant, in association with enhancement of BDNF expression and inhibition of neuroinflammation, being superior to venlafaxine [1].

 

It is traditionally used for treatment of alcohol hangovers. It has been demonstrated that dihydromyricetin may exhibit the protective effects against alcohol intoxication and alcohol tolerance. The molecular mechanism might be associated with competitively binding of dihydromyricetin to BZ sites on GABAARs [2].

 

DHM exerts antidiabetic effects without causing excessive body weight gain via inhibition of PPARγ phosphorylation. DHM might be a useful drug for use in type 2 diabetes insulin resistance therapy [3]

 

Dihydromyricetin may reduce Aβ peptide production and restore gephyrin levels, GABAergic transmission, and functional synapses, leading to improvement of clinical symptoms in Alzheimer's disease. It is a potent neuroprotective agent for DA neurons by modulating the Akt/GSK-3β pathway and may be useful in Parkinson's disease [4]

 

It is a potent natural NF-κB inhibitor and likely a useful therapeutic agent for inflammatory diseases

 

While dihydromyricetin exhibits health-benefiting activities with minimum adverse effects, DHM has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4, CYP2E1 and CYP2D6. Further clinical studies are needed to evaluate the significance of this interaction.

 

[1] https://www.ncbi.nlm.nih.gov/pubmed/29058041
[2] https://www.ncbi.nlm.nih.gov/pubmed/22219299
[3] https://www.ncbi.nlm.nih.gov/pubmed/27984083
[4] https://www.ncbi.nlm.nih.gov/pubmed/27374489


 

Edited by Alchemica

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Finally meet Gardenia fruit.

 

The fruit is the main medicinal part of the plant. Gardenia tea can be used for yin deficiency disorders, which include irritability, restlessness, sensations of tightness in the chest and insomnia. Gardenia is also used in formulas to treat anxiety. In TCM, Zhi Zi recommended dosage is 3 to 12 g daily.

 

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10g Gardenia jasminoides fruit in tea - Not the nicest tasting tea but I'll see what I think of it. You can see the saffron-like apocarotenoids constituents in solution

 

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Baseline mood is a background of 'yin deficiency', just too much heavy negative cognition, too much rigid analysis etc and I'm quite anhedonic. I've been struggling, forcing myself to do things and playing with diet just to manage life a bit, I could seriously do with a bit of stronger plant medicine. I'm just struggling with totally dyregulated stress responses, sleep problems and affective issues that aren't getting better by themselves.

 

The medical need for rapid antidepressant actions without the limitations of ketamine has lead to a research interest in Gardenia/Yueju which has been characterised using a number of acute, subacute and chronic behavioral paradigms and clinically [1].

 

As preclinical findings indicated this plant showed ketamine-like rapid antidepressant effects, and as a polyherbal formal (Yueju) which had antidepressant potency in a relatively rapid manner clinically [2].

 

Results from an experimental investigation uncovered ketamine-like rapid antidepressant effects - increased BDNF expression, in parallel with its rapid antidepressant efficacy in behavior paradigms and Involvement of normalised NMDA receptor and mTOR-related signaling [3] in rapid antidepressant effects, along with epigenetic DNMT1 activity [4]: acute administration of Yueju rapidly attenuated depression-like symptoms in learned helplessness paradigm and novelty-suppressed feeding test, tasks which normally require chronic treatment of SSRI to exhibit antidepressant efficacy.

 

In a chronic mild stress model that mimics clinical depression, a single administration of Yueju also showed rapid and lasting antidepressant effects similar to ketamine. These findings suggest that Gardenia/Yueju may be potentially used as a rapid antidepressant in the clinical setting.

 

The primary active components of gardenia are iridoid glycosides (mainly geniposide and gardenoside), chlorogenic acid, and ursolic acid. In a water-ethanol commercial extract of the fruits, gardenoside and other iridoids made up 70% of the extract, chlorogenic acid 20%, and ursolic acid 10%. In addition, a complex iridoid glycoside, crocin, is the yellow pigment seen in the fruit.

 

The yellow pigment causes immediate antidepressant responses, dependent on synthesis of proteins, including synaptic proteins. This was followed by enhanced expression of CREB and BDNF, which likely mediated the persistent antidepressant responses in solution, these have very rapid antidepressant effects in animal models [5]

 

[1] https://www.sciencedirect.com/…/artic…/pii/S0378874116318086
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654702/
[3] https://www.nature.com/articles/srep13573
[4] https://www.ncbi.nlm.nih.gov/pubmed/29522357
[5] https://www.ncbi.nlm.nih.gov/pubmed/27203575
 

Update:

Seems to have a cumulative effect when used in combination pills, effects becoming quite evident by day 3: Post hoc tests indicated a significant improvement for experimental group over control group from the 3rd day to the 7th day of treatment

https://www.ncbi.nlm.nih.gov/.../figure/f2-ndt-11-2013/


The Gardenia fruit seems pleasant so far (3 hrs), maybe a balancing energy over an uplift so far. Had the water soluble portion first and enjoyed that, then thought I'd ingest the pulp for maximum benefits which caused a bit of GI disturbance. Went to connect with and nurture the Gardenia plants I had growing after having the tea and that was nice then went for a nice river walk.

Gardenia jasminoides is said to have the energetic properties, in more Western though, of: Releasing stress and worry, encouraging you to have fun, bringing joy and playfulness. It's said to target the root, heart and crown chakras.

Modern studies have indicated G. jasminoides showed positive effect in treating type 2 diabetes mellitus (T2DM).

Numerous studies have confirmed that crocins and iridoid glycosides had effects of antioxidation, anti-inflammatory, anti-atherosclerosis, neuroprotective/anti-ischemic brain injuries, anti-platelet aggregation, anti-hyperglycemia, anti-hyperlipidemia, anti-hypertension, and so on. It had functions of learning and memory improvement. There is concern about hepatotoxicity at high doses.


"If we all did value Yin energy a bit more, we would be receptive to new ideas, to new people, to the actual attainment of prosperity and the experience of love."

"Lifestyle patterns and the environment begin to consume Yin over the years. Stress and
other emotional strains can lead to Yin depletion

When one’s yin is replaced, the body’s ability to heal itself is enhanced dramatically. Herbs and foods nourish yin energy, but nourishing yin is not as simple and easy as popping a pill.

Optimal productivity/Yang must have equal and opposite quieter times of rest, rejuvenation and planning.

Nourishing yin requires mindfulness — mindfulness in how you spend your energy, mindfulness in what you eat and mindfulness in feeding your spirit."

The nature of any entity, living or not, is determined by the intrinsic balance between opposing states, Yin and Yang. Disturbances in balance result in changes in nature, often expressed in living systems in the form of symptoms or signs of disease. TCM treatments are intended to restore balance. Balance is accomplished by influencing the vital energy, the Qi. In the TCM paradigm, Qi flows through channels in the body and in the spaces between muscles and the skin. Qi has many functions including warming, moistening, and nourishing; promoting normal function of the organs; providing energy for different processes; regulating the body; protecting the body; and ensuring that organs remain in their proper positions. A very important role of Qi is in maintaining balance. In this sense, it is a homeostatic mechanism by which the body can heal itself and establish a state of wellness. If Qi encounters a Yin–Yang imbalance, Qi corrects the situation by transforming one to the other, thus restoring balance and harmony. If, however, a blockage exists that impedes the flow of Qi, a factor is present that is interfering with the Qi, or if there is a Deficiency of Qi, this healing transformation does not take place. There are TCM techniques for opening blocked channels; for expelling pathogenic factors that are interfering with normal processes; and for boosting Qi in cases of Deficiency

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870484/


 

Got a good gauge of the Gardenia. I think you could easily come up with an effective herbal antidepressant/anxiolytic centred on Gardenia, perhaps with Lotus embryo and Radix Polygalae which may have rapid-onset antidepressant effect which can be a safer alternative to ketamine and lead to the development of life-saving medications.

 

Day 2: There hasn't been super acute robust elevation notable yet with the intake of Gardenia at higher TCM-style doses but some element of simple contentedness is slowly creeping in.


 

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Edited by Alchemica
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Sceletium tortuosum is the most effective natural anti-depressant & anti-anxiety plant I have come across.

It has been shown to have SSRI-like action, and does have reverse tolerance (i.e the more regularly you take it the more the dose required for the same effects can be reduced) which also points in this direction imo, like it needs to build up in your system for optimal results like prescription SSRIs.

The risks are much less than with those though obviously, and I have heard of people combining kanna with, say, Escitalopram without complications although I wouldn't recommend it. Kanna has centuries if not millenias of use in South Africa.

I use the fermented powdered plant material as a snuff, and the antidepressant effects are felt almost instantly.

 

It's a great plant to grow as well, and I find the preparation & fermentation process rewarding and that it helps you connect with the medicine.

Makes a great companion plant for cacti, propagates easily from cuttings and it grows pretty fast. Below is roughly 10 months of growth (with 3 months of winter) on the same plant:

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Agreed @MeanGreen, I've had good experiences with sceletium, I'd rank it much better than most conventional antidepressants for it's dual serotonergic/PDE4 mechanism but also times when it's seemingly 'pooped out' or just given me a kind of sleepless elevation. There's seemingly so much difference between different extracts, too. That's why I've kind of been exploring other things with different mechanisms of action.

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Gardenia vs Saffron





 





As for the Gardenia, today is the last session I'll have with that for a bit, likely pursue it more later down the track when I get more, only bought a small quantity. As seen in clinical studies, I'm maybe noting a mood improvement.





 





It's hard to attribute a sole effect to it as I've been using Gardenia in the morning and then unwinding in the evening with Lotus but my initial impressions of it as a medicine from the days I've had with it:





 





Fairly acutely, It seemingly has some energetic balancing qualities but I think saffron is potentially more uplifting - there's a slight beneficial quality I attribute to the dopaminergic activity of saffron, I didn't get that with Gardenia at the TCM-style doses and I don't want to dose too high on it.





 





Despite both being crocin sources and the gardenia containing beneficial iridoids, I find the saffron has potentially more mood effects than the Gardenia at the doses I used but I've used more saffron than Gardenia so have a greater attunement to it's qualities.





 





I'd say the Gardenia at higher TCM doses builds a foundation of greater balance, a somewhat harmonising energy, the traditional medicinal actions attributed to gardenia include calming irritability; cooling and clearing away heat (a yin/yang imbalance often characterized by deficient yin). The saffron on the other hand is what I'd call dose dependently a spiritual energiser when used correctly. They're both useful but I'm going to stick with saffron in the morning for a bit and re-visit Gardenia a bit later.





 





"Saffron is a spiritual and energetic food ... it can affect so much change and offer incredible healing to the body/mind/spirit complex. Through balancing, the energetic body is also brought into cooperation wherein the associating masculine and feminine energies are able to more fully work together."





 





In Ayurvedic Medicine, it helps to enhance qualities of love and spirituality.





 





Saffron currently has a larger clinical body of evidence for neuroprotective, procognitve, anxiolytic and antidepressant effects with preclinical anti-psychotic effects. While Gardenia has preclinical cognitive improvement in studies, there seems to be a decent clinical improvement in cognitive functions with saffron. It was found to be as effective as donepezil for treatment of mild-to-moderate AD. The beneficial effects of saffron on memory have also been suggested to be mediated by the cholinergic system





 





An interaction with glutamatergic system for saffron and its components might be postulated involving NMDAR modulation, there is functional interaction between crocins and the DAergic system. C. sativus and its constituents increased dopamine levels in the brain in a dose-dependent manner. It also interacts with the opioid system


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