Alchemica

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 glycosides—geniposide 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.

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.

This year, there have been a couple of articles focusing on the immunological and whole body aspects of Sceletium. This extends it's use beyond depression, anxiety and cognitive decline to a greater context of stress, obesity, diabetes and hypertension. Sceletium tortuosum may delay chronic disease progression via alkaloid-dependent antioxidant or anti-inflammatory action. Sceletium may be beneficial for the attenuation of cytokine-induced depression, as well as in systemic low-grade inflammation. Sceletium tortuosum extracts may be employed as either a preventative supplement or complimentary treatment in the context of obesity and diabetes See also here We also see immunological benefits, ultra-potent blockade of proinflammatory markers like TNF-α at pM levels (sub-psychoactive doses) with some 5-HT2AR agonists like (R)-DOI which is promising on many levels, it plays a key role in inflammation, its production and signaling contribute to many inflammation related diseases. An exciting new therapeutic avenue in which 5-HT2A agonists might be employed is the modulation of inflammation. While most of their research is based on (R)-DOI, they are currently testing for the impact psilocybin and other tryptamines. "We have shown that 5-HT2A receptor stimulation with the agonist (R)-DOI rapidly inhibits a variety of proinflammatory markers mediated by TNF-α acting at its receptors, including ICAM-1, VCAM-1, and IL-6 gene expression, NOS activity, and nuclear translocation of NF-κB, with IC50 values of only 10-20 pM. Significantly, proinflammatory markers also can be inhibited by (R)-DOI many hours after treatment with TNF-α. With the exception of a few natural toxins, no current drugs or small molecule therapeutics demonstrate a comparable potency for any physiological effect. TNF-α and TNF-α receptor-mediated inflammatory pathways have been strongly implicated in a number of diseases including atherosclerosis, rheumatoid arthritis, psoriasis, type II diabetes, irritable bowel syndrome, Crohn's disease, and septicemia (e.g., Reimold, 2002; Popa et al., 2007; Williams et al., 2007). Significantly, TNF-α and other cytokine induced inflammatory pathways also have been linked to psychiatric conditions such as depression and bipolar disorder (Dunn et al., 2005; Kim et al., 2007), as well as schizophrenia (Saetre et al., 2007), and neurodegenerative diseases like Alzheimer's and Parkinson's disease and stroke (Tweedie et al., 2007). ...therapeutic strategies that are aimed at blocking the TNF-α receptor-induced signal transduction pathways by 5-HT2A receptor activity would aim at any tissue cell expressing TNF-α receptors, which include most cell types in the body (e.g. smooth muscle cells, neurons, skin cells). Their strategy is to develop 5-HT2A receptor agonism as a viable treatment modality against asthma and other inflammatory disorders. See patent There's plenty of other plant medicines like this, we need to see plants medicines beyond neurotransmission and reductionist terms to a more holistic view, another one that interests me is Ashwagandha. Withaferin A, often considered a less desirable withanolide found in the leaves to a high level, can be used against innate inflammations via TLR4, this is intriguing as these sorts of things drive lots of pathology, for example an immunological aspect seems to strongly drive addictive behaviours. TLR4 is a novel regulator of neuronal physiology and associated drug-reward learning. TLR4 acts as an amplifier for addiction to a wide variety of substances. Altering TLR4 signalling attenuated alcohol abuse behaviour, with extension to opioids, cocaine, and methamphetamine.

This intrigues me, there's interest in saffron, be good to see some solid measure of Positive/Negative symptom outcomes, cognitive domains, alongside metabolic parameters in further studies, hope they go to some depth. " Medicinal plants are among the adjunct alternatives that could reduce the clinical complications and adverse effects of current treatments especially for people with schizophrenia. Saffron, a well known spice, has several potential therapeutic properties including antioxidant, antihyperglycaemic and anti-obesity effects. In addition, saffron has demonstrated tolerability and few adverse effects in human and animal studies (Kianbakht 2011; Mashmoul 2013; Fadai 2014; Kianbakht 2015). With these pharmacological properties, saffron and its bioactive constituents could be considered as an adjunct treatment for reducing metabolic syndrome symptoms. There is currently no evidence on the clinical efficacy of saffron for people with schizophrenia, and this review will evaluate the evidence available for using herbal supplements in managing prevalent adverse effects of current treatments for schizophrenia." [1] Not only does saffron have established efficacy and good safety for treating mental health conditions including depression, anxiety, OCD and high potential in neurodegenerative conditions but it may be helpful for more serious mental illness and induced metabolic disorders. Constituents of saffron are potential agents for the treatment of schizophrenia Added to satiety enhancing and beneficial metabolic effects, it may target comorbid symptoms and impacted domains including addressing anxiety, depressive, OCS, cognition/memory, target negative symptoms (including social withdrawal) and provide neuroprotection against further declines. Added to this, crocins have the ability to attenuate psychotic-like behaviours in animal models, potentially alleviating positive symptoms. - crocins displayed pronounced antidepressant and anxiolytic-like effects - these compounds attenuate HPA axis reactivity after traumatic stress - Saffron constituents were able to attenuate the social isolation induced by sub-chronic treatment with ketamine - crocins were found to reduce compulsive behaviour - Acute administration of crocins reversed recognition memory deficits produced by the NMDA receptor antagonist ketamine in rats eliciting, thus, the effects of this active constituent of C. sativus in schizophrenia-related cognitive deficits. Crocins attenuated ketamine-induced psychotomimetic effects (hypermotility, stereotypies and ataxia) Saffron extracts and crocin administered at 15 mg twice daily were safe and well tolerated in schizophrenic patients. My life has been exploring the pharmacopeia, and the phytocopeia. Definitely got better results with the phytocopeia. Another recommendation was grabbing some seaweed to make salads with. I bought a "50% fucoxanthin extract" but I wasn't convinced it was what it said it was. Likewise I've bought 'pure lutein', wasn't convinced it was what it said, even visually. I prefer my plant sources to many extracts, at least I can munch some marigold flowers, chew down kale, buy some saffron, make a seaweed salad, get stuck into some colourful veggies. Seaweed I'm keen to find some cheap sources of. More on carotenoids: Lutein, a carotenoid found in fruits and vegetables, has long been associated with eye health. Recent studies have found that this nutrient may also help slow cognitive decline. This pigment or carotenoid may play an important role in the development and maintenance of brain function while improving memory and learning. Accumulating evidence has shown that lutein may influence various aspects of brain function ranging from visual-motor to executive functions. Being lipid-soluble, lutein easily passes the blood-brain and blood-retinal barriers and tends to deposit within central nervous system tissues with high specificity. Research indicates it likely reduces inflammatory and oxidative stress while simultaneously stimulating regenerative processes. Recent research found the level of lutein in children relates to how efficiently and accurately their brain works, marking a significant step forward in our understanding of the impact of lutein on children's cognition. It allows us to better understand the impact nutrition, and specifically lutein, has on learning, memory and even academic performance. In younger individuals, supplementing lutein increased systemic levels of BDNF. A number of clinical trials have shown, mostly in the young, that supplementation increases visual processing speed and reaction times. Although there is no direct data on mechanism, it has been speculate that this influence on processing speed is due to direct effects on brain connectivity, perhaps by enhancing gap junctions between neurons. A past study has shown that brain concentrations of lutein associate with higher cognitive test scores in the elderly prompting the possibility that increasing intake could lead to benefit. Lutein appears appears to benefit neurocognitive function by enhancing cerebral perfusion, even if consumed for a discrete period of time in late life. A fMRI study found lutein appeared to buffer cognitive decline on the verbal learning task. Significant interactions during learning were observed in left dorsolateral prefrontal cortex and anterior cingulate cortex. Participants receiving the active lutein supplement had significant improvements in complex attention and cognitive flexibility domains, relative to participants taking the placebo. Seaweed for fucoxanthin etc: Phytochemical research reports exhibit a plethora of chemical compounds from brown seaweeds, including sulfated polysaccharides and fucoxanthins. Fucoxanthin is abundant in seaweed and is considered as a powerful antioxidant. It has been proposed to possess anti-cancer, anti-obesity and anti-diabetic effects. It is neuroprotective and anti-neuroinflammatory, decreasing the pro-inflammatory factor production. Fucoxanthin isolated from the brown seaweeds reduces TNFα, inducible nitric oxide synthase and COX-2 which are important inflammatory cytokines responsible for eliciting depression. Fucoxanthin regulates Nrf2-autophagy pathways and increases neuroprotective molecule expression in models of neurodegenerative diseases. Extracts acted as antidepressants on 5-HT, DA and NE systems. Nice sustainable functional food option. "Fucoxanthin is a brown seaweed pigment that is found in most brown seaweeds, as well as a few other marine sources. It is a xanthophyll, which is a molecule structurally similar to beta-carotene and vitamin A; yet fucoxanthin does not possess vitamin-like activity in the body. Fucoxanthin, via its metabolites, seems to be stored in fat cells for a prolonged period of time and can induce fat loss while inhibiting fat cell differentiation and proliferation. Although only one human study has been published, it appears to be a promising non-stimulatory fat loss agent but requires time to work (5-16 weeks). It also possesses other health benefits, such as correcting abnormalities in glucose metabolism in muscle tissue which can help diabetics and might reduce cholesterol levels and triglycerides by currently unverified mechanisms. Reductions in blood pressure and reductions in both liver fat stores and liver enzyme values have been noted with fucoxanthin supplementation in humans. Fucoxanthin, although usage as a supplement is preliminary, appears to be a very promising joint fat loss and health boosting agent." Some studies suggest that a daily dosage of 2.4-8mg fucoxanthin has shown benefit in some human studies over a prolonged period of time but that's mainly weight benefits and peripheral stuff. That said, the bioavailability is low (but may be improved by consuming in oil)

Why am I throwing polyphenols in there like there's no tomorrow? Polyphenolic Compounds Alter Stress-Induced Patterns of Global DNA Methylation in Brain and Blood. "...polyphenols may promote resiliency to stress and may be an efficacious alternative to traditional pharmacological treatments in psychiatry." ...as I munch down my top up dose... I've mentioned how some polyphenols promotes resilience to stress-mediated depression/anxiety phenotypes in animal models. This one focuses on anthocyanins and dihydrocaffeic acid. Dietary polyphenols and many other dietary phytochemicals are becoming increasingly attractive as therapeutic agents because of their safety and efficacy in alleviating psychiatric symptomology. Plant-derived polyphenols are naturally occurring micronutrients that have demonstrated efficacy in treatment of depressive-like symptoms Changes in DNA methylation elicited by stress are known to be long-lasting and can even span generations in both the CNS and periphery. Stressful experiences can alter DNA methylation patterns in humans and animals, both globally and at gene loci important for brain plasticity and emotion. These methylation patterns can affect expression of genes involved in the crosstalk between inflammatory pathways and neural activity, ultimately conferring vulnerability to psychopathology including depression and anxiety. DNA methylation can be. catalyzed or reversed by environmental factors and persist long after the initial insult, producing stable changes in gene expression during both development and adulthood Once again, these compounds, are looking effective. Stress-susceptible mice display increased inflammation. These compounds show the same demethylating effect in both humans and mice. Global changes in methylation have the capacity to alleviate depressive-like behaviour, which suggests that polyphenol treatment, which elicits large changes in global methylation in the brain and blood, may do so as well. http://sci-hub.tw/10.1002/mnfr.201700722

In the R&D lab this morning. Berry Choc + Therapy. I've gotten slack, just skulling or taking polyphenol sources, not creating with them. This is a simple healing creation. Quite tasty, remember polyphenols tend to have as literature unfolds, synergistic effects, add the rest of the constituents... Because the effects seem to build up, it seems better to have your therapeutic polyphenols etc in the morning IMO. See: Why nutritional psychiatry is the future of mental health treatment This one's the therapeutic blueberry, sour cherry, pomegranate concentrate and cinnamon topped with organic Matcha green tea high flavonol ethical cacao and therapeutic saffron, Clary Sage, Lemon Balm chocolate. Blueberries: Single-dose flavonoid interventions have produced improvements in attention, inhibition, visuospatial memory, and executive function between 2–6 h post-consumption, whilst supplementation of flavonoids for 1.5–8 weeks has been associated with improved visuospatial memory and improved long-term memory. Acutely, a flavonoid rich blueberry drink improved the mood of healthy children and young adults. In both studies, increased Positive Affect was observed 2 h after consumption of the flavonoid-rich drink (significant drink by session interaction). The flavonoid drink had no effect on Negative Affect. In older populations, addition of easily achievable quantities of blueberry (equivalent to one cup) to the diets of older adults can improve some aspects of cognition, including executive functioning. Supplementation with an anthocyanin-rich blueberry concentrate improved brain perfusion and activation in brain areas associated with cognitive function in healthy older adults. A single dose increased positive affect. Pilot EEG data highlight an anxiolytic effect of the consumption of a single serve of berries, as indexed by a suppression of α spectral power, and an increase in the slow wave δ and θ spectral powers. There was also an indication of greater alertness and lower fatigue, as indexed by an increase in β power and suppression of α spectral power. They cause an acute increase in reaction times during the digit vigilance task. Longer term, in a cognitively impaired population, Improvements in verbal fluency, short-term memory and long-term memory are observed. There tends to be blood pressure reduction. They have really good anti-obesity/hypoglycemic/hypolipidemic and antidepressant-like effects. They tend to be insulin sensitising It's not just that they improve hippocampal neurogenesis and function. Berries have the potential to decrease memory impairment, oxidative stress status, and AChE activity and increase neuron density etc. Anthocyanins increase BDNF mRNA expression and may alter other important cognitive pathways. Pomegranate see here Cinnamon: The bark contains proanthocyanidins, catechin and epicatechin along with the precursor for benzoate, cinnamaldehyde. Cinnamon could be beneficial to counteract deleterious dietary effects in stressed conditions. It could effectively prevent the cognitive dysfunction and the impairment of energy and glucose homeostasis induced by amyloid-β deposition by reducing neuroinflammation and enhancing insulin signaling. It efficiently inhibits tau accumulations, Aβ aggregation and toxicity in vivo and in vitro models. Indeed, cinnamon possesses neuroprotective effects interfering multiple oxidative stress and pro-inflammatory pathways. Cinnamon modulates endothelial functions and attenuates the vascular cell adhesion molecules. Cinnamon PPs may induce AD epigenetic modifications. Cinnamon seems to be effective and safe approaches for treatment and prevention of AD onset and/or progression. "A Cochrane review on cinnamon states that long-term blood glucose control is essential in reducing the risk of complications associated with diabetes mellitus such as cardiovascular disease (CVD), retinopathy and nephropathy. Insulin is one of the key hormones that regulates energy and metabolism use as well as transporting sugar from the bloodstream into cells. Cinnamon has been studied as a therapy for improving glycaemic control through its insulin-mimicking biologically active properties that enhance glucose uptake and utilisation in the cell by: -modulating hepatic glucose metabolism through changes in pyruvate kinase (PK) and phosphenol pyruvate carboxikinase (PEPCK) -inhibition of intestinal glycosidase -translocation and synthesis of glucose transporter 4 (GLUT-4) -insulin receptor de-phosphorylation and auto-phosphorylation. In type 2 diabetes, higher amounts of glycated haemoglobin (HbA1c) are indicative of poorer control of blood glucose levels. Once haemoglobin has been glycated, its ability to transport oxygen, as well as collect carbon dioxide to return to the lungs, is lost leading to advanced glycated end product (AGE), elevated HbA1c and plasma glucose which are associated with retinopathy, nephropathy and cardiovascular disease. In a clinical trial, 2g of cinnamon a day for 12 weeks alongside regular medication for type 2 diabetes, significantly reduced glycated HbA1c, as well as diastolic and systolic blood pressure compared to placebo.A recent double-blind trial reported that 3g of cinnamon significantly improved all components of metabolic syndrome such as insulin, blood pressure, antioxidant status and lean body mass when compared to a placebo" Cacao and butter Alongside the dose-dependent cognitive enhancement, the cacao flavonols help with the NO, CBF and BDNF and general brain health, and cardiovascular benefits, data suggest that (-)-epicatechin exerts its antinociceptive effects by activation of the NO-cyclic GMP-K channels pathway, 5-HT1A/1B/1D/5A serotonergic receptors, and μ/κ/δ opioid receptors. Total plasma concentrations of (−)-epicatechin plus (−)-epicatechin metabolites were found in the low-micromolar range as soon as 1 h after the consumption of a flavanol-rich food. The major metabolite of (−)-epicatechin detected in plasma was 4′-O-methyl-epicatechin-7-β-D-glucuronide NF-κB, phosphatases, and kinases, other signaling cascades have been shown to be modulated by (−)-epicatechin and procyanidins. Oral (−)-epicatechin administration to mice protects against Aβ-induced hippocampal toxicity and from stroke-associated brain infarcts and neurologic deficits. At nanomolar concentrations, (−)-epicatechin stimulated the Nrf2 signaling pathway in primary cultures of astrocytes and neurons " Epi is now known not only as an antioxidant and activator of NO production but also as a substance that can enter the brain and supposedly provide neuroprotection.. Furthermore, Epi's anti-inflammatory effects, its ability to prevent metabolic abnormalities, its ability to reduce infarct size in the heart and stroke volume in the brain, its ability to improve red blood cells' deformability and to reduce pro-thrombotic states, all provide it with a unique synergy in mechanisms involved in the prevention of hypertension and concomitant cardiovascular and brain-related diseases. This may result in significant health benefits and longevity. Thus, Epi, due to its multiple biological activities, is a promising therapeutic candidate ...a high intake of flavonoid-containing foods was associated with better cognitive functions at baseline and also with a more favourable evolution of cognitive performance after a 10-year follow-up period. In a crosssectional study, the relationship between the intake of foods containing chocolate, wine and tea and cognitive performances in elderly people showed dose-dependent associations between the consumption of these foods and cognition (Nurk et al., 2009). In another study, more frequent chocolate consumption was significantly associated with better performances on the extensive battery of neuropsychological tests. Interestingly, the associations between frequent chocolate consumption and cognitive performance remained significant after adjustment for a number of cardiovascular risk factors, including hypertension (Crichton et al., 2016). Furthermore, a high dose of cocoa polyphenols improved self-rated calmness and contentedness Experimental studies suggest that orally administered Epi may be a potential prophylactic for Alzheimer's disease in mice (Cox et al., 2015) and, in snails, may enhance memory formation if applied during memory consolidation (Fernell et al., 2016). Additionally, orally administered Epi may affect anxiety-like behaviour in mice" [ref] These fatty acids have effects, from GABAA modulation in some blends to the oleic acid which involves modulation of DA and serotonin neurotransmission Some of the fatty acids are interesting at opioid receptors, too: The mixture of linoleic and palmitic acids (1:1) showed an affinity for δ opioid receptor with a Ki value of 9.2 ± 1.1 μM. Cocoa butter is rich in palmitic and ~4% linoleic. Green Tea Tea consumption had significant acute benefits on mood and performance and creativity. While some suggest taking supplements of green tea to reduce metabolic biomarkers alone is ineffective, as part of a diet shift it seems good. Tea use was associated with reduced stress, increased calmness and increased electroencephalographic activity (increased alpha, beta and theta activities) in the midline frontal and central brain regions Green tea consumption in subjects with cognitive dysfunction (2 g/day for 3 months, approximately equal to 2 to 4 cups of tea/day) significantly improved cognitive performance. Along with the effects of lower doses of caffeine and small quantities of L-theanine, EGCG has sedative effects in the brain, partially through GABAA receptors, and consequently moderates an acute stress response in a dose dependent manner. Green tea is believed to lower the risk of dementia both through it's polyphenols and active metabolites that exhibit effects on nerve cell proliferation and neuritogenic properties. The consumption of green tea catechins is generally believed to suppress age-related cognitive dysfunction, The neuroprotective, antioxidant, anti-inflammatory, and iron-chelating properties of epigallocatechin gallate (EGCG) make it promising for neurorescue. Diet induced neuroinflammation was restored by EGCG supplementation and homocysteine-induced neurodegeneration and neuro-inflammation in the brain was attenuated. It inhibits brain damage and promotes regeneration in the cerebral cortex of rats. EGCG was able to effectively inhibit chemical-induced neurodegeneration and improve learning and memory retention in some toxic exposures Teas significantly reduced AChE activity and partially reduced fat accumulation. Green teas reduced memory deficits. They reduced reactive species accumulation and reduced plasma triglyceride levels. The tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been shown to ameliorate metabolic abnormalities and fatty liver. Saffron: Saffron (Crocus sativus L.) has demonstrated antidepressant effects in clinical studies and extensive anxiolytic effects in experimental animal models. It reputedly has acute effects. It's not overly expensive to get a bulk decent quality Iranian saffron from the right places. Quite quickly, it increases mood, reduces anxiety and manages stress without side effects in studies. It has been traditionally used for the treatment of insomnia and other diseases of the nervous systems, it has sleep quality improving effects. Crocins attenuated schizophrenia-like behavioural deficits. It has a satiating effect and decreases the frequency of snacking events. It's been used in emotional disorders and it was found that using saffron (30 mg/day) was effective in relieving symptoms in some cases. Crocin can regulate HPA axis activity and has therapeutic effects in stress disorders, potentially PTSD where it is effectve in an animal model. It may serve an appropriate treatment for subjects who experience a extremely stressful or traumatic event. Saffron and its metabolites have proven to be effective in different models of psychiatric disorders, including depression and anxiety. It is as least effective as first-line medications for MDD in quality studies with less side effects. It's got a good safety margin, while 30mg may prove effective “to a daily maximum dose of 1.5 grams there has not been any risk documented. Lethal dose is 20 g and the abortive dose, 10 g, because as such it was employed in the past due to its stimulating action on the smooth muscle of the uterus. 5 g daily dose can already cause intoxication accompanied by vomiting, bloody diarrhea, hematuria, skin hemorrhages in nose, lips and eyelids, vertigo and dulling. The skin and mucous membranes take a yellowish colour similar to jaundice”. Crocin is an isolated chemical compound that belongs to a group of commercial carotenoid derived from the stigma branches of dried saffron. The spice’s high antioxidant capacity explains most of its preventive or healing properties in relation to chronic and degenerative diseases Crocin and crocetin may have a neuroprotective effect because of their anti-inflammatory action in microglial cells, as tested in rat brains, accompanied by a reduction in neurotoxic molecules (TNF-α, interleukin-1β and intracellular ROS. The restoration of a redox balance in brain tissues can be a good therapeutic strategy to limit neuro-inflammation and consequently tissue oxidative damage). Many of the anti-inflammatory effects of crocin demonstrated in animal models of neuronal degeneration could be mediated by its direct effects on microglia homeostasis. It also has anti-adiposity effects Crocin can be considered as healthcare product to prevent age-related brain diseases, it is able to enhance memory function in an aging model through anti-glycative and anti-oxidative properties which finally can suppress brain inflammatory mediators and increase protective pathways Crocin can improve learning and memory and may prevent neurodegenerative disorders including Alzheimer's disease. Saffron is a source of novel acetylcholinesterase inhibitors. It is not mutagenic and prevents alcohol-induced disorders of memory and learning. Its mechanism is thought to be prevention of the inhibitory effect of ethanol on N-methyl-D-aspartate (NMDA) glutamate receptors in the hippocampus. It has clear binding capacity at the PCP binding side of the NMDA receptor and at the sigma(1) receptor There is an anti-fatigue effect of crocetin - its intake improved performance when taken 4 h before a physical fatigue-inducing task Treatment with saffron extract for seven consecutive days in a study conducted in rats in an experimental model of MS improved learning and memory impairment and alterations in the parameters of oxidative stress in the hippocampus. Clinically saffron was able to reduce MS symptoms - crocetin might prevent demyelination and neurodegeneration. Such findings show that saffron may potentially prove useful in the treatment of MS through the inhibition of oxidative stress and the infiltration of leukocytes to the CNS. Saffron protects many cells of the dopaminergic system with relevance to Parkinson's disease. Studies on the bioactive substances of saffron in depression indicate that the crocin acts by inhibiting the reuptake of dopamine and norepinephrine neurotransmitters, while safranal inhibits the reuptake of serotonin. There are in vivo studies suggesting inhibitory effects on the monoamine oxidases, MAO-A and MAO-B, enzymes responsible for the degradation of the neurotransmitters, as mentioned above, leading to an increase in their levels in the synaptic space and reducing depressive symptoms. 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] [1] https://www.ncbi.nlm.nih.gov/pubmed/27701683 [2] https://www.ncbi.nlm.nih.gov/pubmed/28735826 [3] https://www.ncbi.nlm.nih.gov/pubmed/29062366 Clary Sage I've also used quite a lot of Salvia sclarea essential oil orally at low doses. It adds nicely to food, in contrast to lavender. I find it nicer than lavender in effect, too. Lavender has effects in part mediated by 5-HT1ARs, likewise the linalool-type compounds in Clary sage probably do too. These compounds also reverse the epigenetic consequences of stress Clary oil was found to alleviate stress and have antidepressive effects, effects manifested by activation of dopamine pathways. The anti-stressor effect of clary oil likely involves dopamine D1/D2 and 5-HT1ARs. "Another piece of research published in the Journal of Medicinal Food found that including clary sage oil in the food of animal subjects lead to a significant reduction in dominant and anxious behavior. " https://www.medicalnewstoday.com/articles/320423.php Lemon balm Elliott et al. (2007) employed EOs from Lavandula angustifolia Mill. and Melissa officinalis L. belonging to Lamiaceae for the management of agitation in individuals with severe dementia. The sedative and calming effect of both EOs is already established which can contribute in consolidation of memory. In the receptor binding capability study, both oils extensively inhibited radioligands binding to the muscarinic M1, 5HT2A, histamine H3 receptors and GABAA receptor channel site. M. officinalis EO displayed broad receptor binding capacity in comparison to L. angustifolia EO, and showed affinity for binding with 5HT1A and the agonist binding site of GABAA receptors. The results of this study revealed that both EOs act as substrate for and interact with several receptors, and can be effectively used to relieve the symptoms of agitation. Conversely, M. officinalis EO has got the ability to reduce social withdrawal times and increased the time of constructive activities of dementia patients. L.angustifolia and M. officinalis EOs in combination (50:50) has inhibited flunitrazepam binding. A placebo-controlled trial, conducted on patients affected by severe dementia guests of care facilities in the UK, reported the effect of Melissa officinalis (M. officinalis) essential oil, applied as massage twice a day for 4 weeks, on agitation measured by the Cohen-Mansfield agitation inventory (CMAI): seventy-one out of the seventy-two participants completed the trial and results demonstrated an improvement of agitation without the occurrence of significant side effects. The efficacy of lemon balm hydroalcoholic extracts rather than the essential oil is also well documented. In a study (a parallel group, double-blind, randomized, placebo-controlled trial), involving aged patients (from 65 to 80 years of age) suffering from mild-moderate AD, 60 drops/day of lemon balm extract were administered. Lemon balm exerted positive effects both on cognition, as measured through the 11-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog) and the CDR-SB, and on agitation as side effect at 4 months.

Today some Kimchi preparation. I used red/purple cabbage - 36 anthocyanins have been detected in this Started them with a quality broad spectrum probiotic I made a few kimchi blends - an isoflavone-rich one (small, just an experiment) - an anti-inflammatory one rich in turmeric, ginger, black pepper, chili etc - one with diverse healing polyphenols/phenolics (incl. catechins from Matcha green tea, anthocyanins from hibiscus, olive polyphenols, dihydromyricetin, p-coumaric acid) Also brewed up some simple lacto-fermentations of Matcha green tea/hibiscus So what am I hoping to achieve with my Kimchi's? The anti-inflammatory Kimchi is fairly simple. These are cheap to whip up, a couple of dollars buys cabbage and I had the other ingredients around. I might make some other varieties today with 'less variables' and more science to them. I've used a good mix of probiotics, including L. plantarum which is of great interest since it possesses enzymes leading to the production of high-added value compounds, such as powerful antioxidants In my polyphenol blend, It has a fair bit of polyphenol rich Matcha green tea, fermenting this converts some of the catechins to new actives, with increased anti-oxidant activity and possibly better effects. It contains olive polyphenols which ferment beneficially. Recent findings in animal models and humans show that polyphenols may have a role in regulating neurotrophins levels, in particular nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF), suggesting that olive polyphenols may also induce their protective effects through the potentiation of neurotrophins action. NGF and BDNF They control oxidative stress, inflammation, apoptosis and mitochondrial dysfunction. Olive polyphenols may increase the levels of NGF and BDNF in crucial areas of the limbic system etc, which play a key role in learning and memory processes and in the proliferation and migration of endogenous progenitor cells. There things like dihydromyricetin "DHM exerts a more rapid antidepressant-like effect than does a typical antidepressant, in association with enhancement of BDNF expression and inhibition of neuroinflammation". It's not established exactly how this ferments, but it's possibly beneficial. There are good levels of hibiscus anthocyanins. Anthocyanins often form gallic acid and protocatechuic acid There is some p-coumaric acid. p-Coumaric acid itself enhances long-term potentiation and recovers learning and memory impairments. It also modulates GABAARs, exerting anxiolytic effects. Hydroxycinnamic acids were the main compounds stimulating the production of volatile phenols by LAB. Some hydroxycinnamic acids showed a beneficial effect on growth of Lactobacillus strains, while inhibiting other strains. This one, I have to see how it ferments... it may form 4-vinylphenol and 4-ethylphenol etc, this might add taste funkiness. The Nrf2 cell defense pathway is stimulated by alkyl catechols including 4-vinylcatechol, and 4-ethylcatechol but probably not by the monophenols. I'm not sure this is an ideal addition, so I might skip it in the next. The turmeric laden Kimchi The turmeric one has started to leach orange actives into solution, like the curcuminoids are being liberated as something more soluble. During fermentation, it is said curcumin transforms into different metabolites which can be more easily absorbed by the body, rather than the whole curcumin molecule, hard to find solid analysis results of fermented turmeric though but there is in vivo evidence that the beneficial activity of turmeric is significantly improved. Today the liquid is bright orange. Then you get your probiotics, too. . The potency of various phytonutrients can also be improved by fermentation. Polyphenols, a specific category of phytonutrients, occur naturally in fruit, vegetables, nuts, seeds, rhizomes, flowers and barks of plants. Fermentation causes a significant increase in the free soluble polyphenol content. Free soluble polyphenols have higher beneficial activities. Fermentation also reduces the amount of non-digestible material in plant foods, leading to improved bioavailability of minerals and trace elements. Lactic acid bacteria also have the ability to increase the antioxidant potential and alter the phytochemical profile. Lactobacillus fermented beverage made from turmeric rhizomes was shown to have an increase in antioxidant activity. Plasma antioxidant concentration was higher in rats administrated the fermented turmeric than the unfermented version, fermentation of turmeric increases its bioavailability. Turmeric has emerging interest world-wide mainly because of its remarkable chemical composition which includes protein, especially globulins and albumins, carotene, fatty acids, flavonoids and phenolics. The yellow colour in turmeric are mainly due to the presence of three major pigments; curcumin, demethoxy-curcumin and bis-demethoxy-curcumin. These curcuminoids are known to have high medicinal activity. Turmeric itself has anti-inflammatory, anti-oxidant, antidepressant activity, and plaque load in the Alzheimer's models and has promise in other neurodegenerative conditions, being potently anti-neuroinflammatory but is limited by bioavailability. The isoflavone kimchi The isoflavone kimchi, which is only a small jar, has really developed quite quickly. That was started with quite high levels of selected probiotics. Lactic acid bacteria and Bifidobacteria, if the strains are right, have the ability to bioconvert the glycosylated isoflavones to more bioavailable aglycones and in what I'm trying to do, daidzein, genistein etc to new metabolites, with superior bioavailability and higher potency at ERβ (the parent molecules are also CNS active as serotonergic 5-HT1A etc mediated antidepressants, anti-PTSD, anxiolytic, anti-seizure) and some with stronger anti-cancer effects (strong inhibitory activity against tyrosine kinases), such as dihydrogenistein, dihydrodaidzein, and equol/5-hydroxy-equol etc. Last lot of fermented batches is the K.I.S.S. batches, still experimental. How healthy can you make a fermented product with only common veggies, herbs and spices? How tasty, too? More a functional food than some exotic creation straight from the 'R&D department'... These attempts are really flavoursome right from the start, with quality nutrition. Not sure how these will ferment, so they're small sizes. While using cabbage as a base, I used lots of onion, parsley (polyphenol sources), still some green tea, bit of garlic and ginger, bit of turmeric, a bit of chili, solid amounts of concentrated tomato for carotenoids etc, tried to bind one with chia, stop the sloppiness. These PUFAs strangely seem to ferment to superior anti-inflammatory substances. Played around with some herbs and spices to get something tasty. Few different attempts, see what happens. You end up with colourful concoctions. That will satisfy my fermentation curiousity, see if I get anything decent. See how it goes.

This is one that spoke to me at the community garden the other day. Enough to want to grow some, as an addition to my garden, companion plant and medicinal tea option. It's a Tagetes, I'm thinking T. erecta.They had sacred status with the Aztecs. I've never tried the more psychoactive version, has anyone here explored to good healing effect? I did make a tea out of a few flowers of this one. Pleasant taste. Mexican marigold resonates with the energy of the sun While Tagetes lucida has a psychoactive action and has been used ceremonially and may be drunk as a tea to promote visions, Tagetes erecta, the marigold, is not just a flower or companion plant, it has ethnomedicinal use. The T. lucida grows at the local Botanic gardens. Might have to explore. Tagetes erecta has promise in the treatment of various ailments, the flower parts of plants have hepatoprotective, anti-oxidant, anti-seizure, antidepressant/anxiolytic and analgesic activity. Data support the anxiolytic and sedative-like properties of T. erecta in traditional medicine by involving mainly serotonergic neurotransmission because of the presence in part of flavonoids and the terpenoid β-sitosterol. Serotonergic, nitrergic pathway, and sigma receptors are possibly involved in mediating antidepressant action of T. erecta. It's a good source of carotenoids (mainly xanthophylls), too. The flowers of Tagetes erecta is considered to be effective in the treatment of epilepsy as in Ayurveda Keen to know if anyone's explored the 'less psychoactive versions' medicinally?

I've got a few T. erecta now - another 'medicinal potted colour' Using Tagetes erecta flowers, sometimes used as a food colour, as a healing dietary addition is nice on many levels. I have a few different ones, some have stronger flavour, others have a super mild flavoured edible flowers that make awesome colourful garnishes that just bring sunshine to your salad, aesthetically and in their chemistry and pharmacology. I'm now getting self-sufficient in having a good healing salad addition growing in my own garden. . I prefer to spruce my salads with them. Not just additional colour 'radiating with the energy of the sun' to brighten your day but flavonoids, triterpenoids and healing carotenoids with CNS benefits and whole body healing effects. Better that way than tea, the taste is mild but pleasant.

If you need another inspiration for a dish, I prepared this one when I was really ill and found it healing: Requiring hardcore culinary arts therapy, prepared a curry from scratch using literature therapeutic doses of medicinal phytochemicals from food. Made a daal cinnamon curry with a good source of coconut MCTs and good fatty acids Curcumin is anti-inflammatory and antidepressive. Blend it with your oil and black pepper. I use a medicinal turmeric that naturally has 5 x the curcuminoids. Ginger and its constituents, such as 6-gingerol, 6-shogaol, 6-paradol, zingerone, and dehydrozingerone, are effective for ameliorating the neurological symptoms of neurodegenerative conditions. Polyphenols from cinnamon I've covered. Added a solid bit of saffron, covered above. Curry leaf aqueous leaf extract reduced the despair behaviour in experimental animal models, suggesting an anti-depressant like activity and also exerted anxiolytic activity Tip: Add some turmeric essential oil, less than 10 drops (anti-inflammatory, ar-turmerone inhibits microglial activation, a property that may be useful in treating neurodegenerative disease. Furthermore, ar-turmerone increases NPC proliferation) It's very flavorsome but I like it. For a more Mediterranean style dish Requiring a bit more of a boost to get into the world (community garden etc, fairly busy tomorrow), whipped up a 'medicinal purple cabbage bolognese'. Used some fresh herb where I could but packed in high levels of dried herb. I certainly don't skimp on my herbs and spices, this is probably the most herb-laden I've spiked a carotenoid-rich tasty tomato sauce, swimming with purple cabbage anthocyanins (no pasta) and other goodness. Epidemiological studies suggest long-term consumption of dietary polyphenols is associated with a decreased risk of incidence of chronic diseases. They are seemingly effective to alleviate inflammation-related diseases, possessing antioxidant, anti-inflammatory, cardioprotective, neuroprotective and anti-cancer health benefits. More recently benefits have been extended to their other CNS benefits While I grow all these, I'm not yet self-sufficient for having medicinal cooking therapy sessions. Heaps of oregano. This contains rosmarinic acid, apigenin, luteolin, quercetin, scutellarein and their derivatives. Not meaning teaspoons or like piss weak quantities. Oregano possesses potent antioxidant properties. Oregano is rich in antioxidants, with as little as one gram could contribute a significant amount of plant-based antioxidants to a human being per day. An extract prepared from leaves of oregano, a major constituent of the Mediterranean diet, is brain-active, with moderate triple reuptake inhibitory activity, and exhibits positive behavioural effects in animal models, not just the carvacrol rich essential oil that is CNS active. High doses of parsley. Alongside the quality nutrition. Parsley is rich in polyphenolic flavonoids, including apiin, apigenin, crisoeriol, and luteolin. Not your standard 'herb' levels Large doses of basil, including some exotic ones. Once again rich in nutrition, polyphenols and flavonoids as well as compounds such as rosmarinic acid Heaps of onion. Onions are among the richest sources of dietary flavonoids. I pack in the dried onion. I like to use a bit of anthocyanin containing red onion, too. Topped it off with saffron. Very tasty. Tip: add a drop of Spanish Sage essential oil to your cooking (established mood and cognitive benefits in healthy individuals)

This might give you some idea. For an extract that exerts beneficial CNS effects: Catha edulis Forsk. (Khat): Evaluation of its Antidepressant-like Activity Although a lot of studies demonstrated that cathinone is unstable and undergoes degradation during drying or extraction and becomes physiologically inactive after about 36 h of harvesting,[8,22,23] the current investigation used standardized extraction method followed by spectroscopic confirmation. The phytochemical analysis (MS of Khat extract) indicated the presence of cathinone and cathine as shown in Figure 1. Previously published studies on the chemical compositions of herbs and their bioactivity recommend that plants containing saponins, flavonoids, and tannins own bioactivity against many central nervous system ailments.[31] Phytochemical data on Khat revealed the presence of many phytochemicals.[32] It is probable that the biomechanism of anxiolytic action of Khat could be due to the binding of cathine or cathinone to various receptors involved in the anxiolysis processes, which has to be explored further. Wont go into isolation of active constituents here.

I've been in Lamiaceae land quite a bit lately, find they're really good healing plants. I'm actually happy if my potted colours are not blatantly psychoactive but instead provide the healing components I seek, flavonoids/rosmarinic acid etc. There's one overgrowing awaiting relationship, it's probably one of the fastest growing ones I've got. If I can use it for a good flavonoid/rosmarinic acid + source, even if it's not particularly psychonautic active, I'm happy. There are very mixed reports from people looking for mind-bending effect. I'm looking in another direction, it being medicinally beneficial... Anyone used it as a health tonic? Coleus blumei is an edible of flowering perennial plant in the family of Lamiaceae used for healing and shamanically. For centuries, the Mazatec Indians of southwestern Mexico have known and used El Ahijado in their religious healing ceremonies. In traditional Mazatec communities, Coleus blumei is considered ‘the male’ (El Ahijado) Sterol and triterpenoid compounds, including abietane type diterpenes, are found in the leaves of Coleus blumei Benth. Flavonoid compounds were also detected in high levels, along with rosmarinic acid. Another analysis found Coleus leaves consisted of flavonoid, steroid, tannin and saponin. Traditional healers use it for diarrhoea as an oral infusion. Coleus blumei has been used to treat many common ailments. Most commonly, the Mazatec used this magical herb to treat stomach pains, digestive problems, dysentery, and even elephantiasis. In other parts of the world the plant is used to treat headaches and ulcers and as a contraceptive to prevent pregnancy (Voogelbreinder 2009, 135) I just like high healing flavonoid etc plants, Coleus grows well and I have an abundance.

Really cool article. We need to learn the subtleties of plant medicines, not just the "opening medicines". Yep, even a diet optimised with the right plants gets psychoactive in a subtly healing way. http://phytoalchemy.co.za/2018/02/14/cross-cultural-technology-healing-consciousness-using-psychoactive-plant-medicines/ "...there appears to be a broad lack of attention in the West to the role of the other major traditional plant medicine categories besides the strong consciousness opening medicines. In this paper I explore the sequential use of subtle acting psychoactive cleansing, opening, strengthening and protection medicines that are indispensable in the successful healing and self-development process that indigenous healers undergo in both South America and Southern Africa, as part of their initiation with psychoactive plant medicines, and that this process can not be understood by focusing on the opening plants... ...the sequential use of subtle acting psychoactive plant medicines is indispensable for the healing process observed in traditional societies, and that Westerners would benefit in recognizing that shamanic healing is not only the use of opening plant medicines..., but a well designed process of using numerous subtle acting psychoactive plant medicines, in a sequence, in order to heal and transform a person, that requires time and patience."

Played a bit around with a strongly purple Coleus, just nibbling bits, nothing too extreme, not a therapeutic dose - those really purple Coleus may theoretically have the highest level of some healthy constituents but that purple colour seemingly stains your mouth quite a bit, particularly your tongue... if you don't want to freak people out, be careful of the purple Coleus.

While well known for it's hepatoprotective benefits, you seldom hear of Milk Thistle being used for other reasons. It has antioxidant, anti-inflammatory, immunomodulating, anticancer, cardioprotective and intriguing CNS effects. I've used this a bit on top of my other polyphenols and some high silymarin extract is cheap. It has anxiolytic and antidepressive effects in brain injury in animal models Back on it at the moment as it's one I've kind of got some bulk powder left of and ran out of other solid polyphenol sources for a bit. It's hard to tell what it feels like alone but I just find it beneficial to keep the polyphenols flowing in my diet, otherwise I get extra sick. Milk thistle (Silybum marianum) is a medicinal plant that has been used for thousands of years as a remedy for a variety of ailments. As a traditional medicine it has been used for treatment of liver diseases and is known to provide a wide range of hepatoprotective effects. It has been found effective in various neurological disorders and things like Rheumatoid Arthritis and diabetic complications. "Clinical trials have shown silymarin is safe at high doses (>1500 mg/day) in humans, the pharmacokinetic studies over the past three decades related to absorption, distribution, metabolism, and excretion of silymarin have revealed poor absorption, rapid metabolism, and ultimately poor oral bioavailability." That said, I feel there's still benefits to use in the diet, You can consider complexes with improved bioavailability. Please note there may be drug interactions, sometimes this can be exploited beneficially. "The neuroprotective effects conferred by silymarin include modulation of various antioxidant mechanisms, and several kinases involved in cell signaling pathways, inhibition of the inflammatory response generated during neurodegeneration, neurotropic effects, regulation of neurotransmitters and inhibition of apoptosis." [1] Aside from being a good anti-oxidant, silymarin, a plant-derived polyphenolic flavonoid of Silybum marianum, elicited significant antidepressant-like activity in an acute restraint stress model of depression. It improved monoamines, mainly 5-hydroxytryptamine (5-HT) levels in the cortex, dopamine (DA) and norepinephrine (NE) in the cerebellum in mice. It alleviates monoaminergic deficits, neurogenesis (enhancing 5-HT, NE and BDNF levels), and attenuation of inflammatory cytokines system and oxidative stress by modulation of corticosterone response, restoration of antioxidant defense system in cerebral cortex and hippocampus. Silibinin-treatment up-regulated the BDNF/TrkB pathway and attenuated autophagy in the hippocampus. Silymarin/silybin reveals immunomodulatory effects with both immunostimulatory and immunosuppressive activities. Different studies have shown that silymarin has the anti-inflammatory effect through the suppression of NF-κB signaling pathway and TNF-α activation. Silymarin attenuated IL-6, and TNF-α significantly It can be considered a potential treatment for Parkinson's Disease and other neurodegenerative diseases associated with neuroinflammation. Silybum marianum could be a new source for the isolation of phytoconstituents useful in cognition and memory disorders such as Alzheimer's disease Silymarin is a potential option for preventing aging and age-related diseases.

Thanks, one day that would be nice, I keep doing little write ups for the moment, I still struggle quite a bit with my head, each day is just trying, so these kind of cognitive tasks help me a little bit. Nice to be able to do little bits and pieces that others find of interest.

It's the same compound in many essential oils, including rosemary. This compound is quite effective via inhalation, as mentioned, anxiolytic, pro-cognitive. Acetylcholinesterase (AChE) and N-methyl-D-aspartate receptor (NMDA) ligands are used in treating cognitive decline such as Alzheimer's, too. Irreversible AChE inhibition is sometimes problematic as you mention. Particularly things like memantine ie uncompetitive NMDAR antagonists with paradoxically cognition enhancing, even antipsychotic-augmenting effects, find use in medicine. That said, it's one you don't want to dose too high on.

I've used pomegranate leaf and brewed some up with my pomegranate peels. This morning a strong brew of pomegranate peels, blueberry, hibiscus and lots of spearmint For holistic health, even in pathology, I still think you can't go past what many people would consider 'not medicine'. Today in the shamanic mug is a nice broad-spectrum, chunky style with the spearmint brew, cocktail of polyphenols etc. Saved up lots of local pomegranate peel. It makes quite a tanniny tasting healing tea with a broad spectrum of healing polyphenols which can enhance cognitive/functional recovery in CNS injury. Tonnes of Spearmint. Added some Hibiscus and a solid dose of blueberry goodness. These tools I think I find healthier and at times more effective than something considered 'more medicinal' All of these constituents are to me nicely uplifting, the anthocyanins improve mood/positive affect even acutely have solid pro-cognitive effects, improving memory aspects and executive functioning etc. These are looking really promising for CNS things: Pomegranate supplementation improves cognitive and functional recovery following ischemic stroke: A randomized trial. These also contains beneficial phenolics and flavonoids I use the whole fruit, the peel of the pomegranate is now being recognised to contain up to three times the polyphenols as the arials. Pomegranate includes: punicalagins condensed tannins catechins gallocatechins prodelphinidins "Use young leaves as a salad green. Use young leaves in a green smoothie or juice. Use young leaves as a spinach alternative – curries, pasta sauces, soups … Make a leaf tea – fresh or dried. Make a paste from the leaf and put it on eczema directly."

I'm a polyphenol fiend. While I started off buying some pomegranate juice which is high in natural sugars with 170mg polyphenols a dose, today I met the tree and connected with the fruit. Using the whole fruit, the peel of the pomegranate is now being recognised to contain up to three times the polyphenols as the arials. This is symbolic of Nurturing through Death, Rebirth and Major Transitions. Pomegranates figure in some way in virtually every religion known to man. The pomegranate, Punica granatum, is an ancient, mystical, unique fruit borne on a small, long-living tree cultivated throughout the Mediterranean region, as far north as the Himalayas, in Southeast Asia, and in California and Arizona in the United States. In addition to its ancient historical uses, pomegranate is used in several systems of medicine for a variety of ailments. It has antioxidant, anticarcinogenic, and anti-inflammatory properties and very beneficial effects on the brain. In Ayurvedic medicine the pomegranate is considered “a pharmacy unto itself ” There are strong esoteric traditions that pomegranate juice can absorb and counteract negative energy. This spiritual use is suggested by some of legends associated with pomegranate in world religion and mythology. Mohammed urged the eating of pomegranate to combat envy and hatred. The Buddha was said to have used pomegranates to calm a cannibal demon. The pomegranate fruit is often used to signify that it is now the “fruit of the Spirit” that controls our lives rather than the lust of the flesh Pomegranate is a potent antioxidant, superior to red wine and equal to or better than green tea. In addition, anticarcinogenic and anti-inflammatory properties suggest its possible use as a therapy or adjunct for prevention and treatment of several types of cancer and cardiovascular disease. Pomegranate juice contains anthocyanins. ascorbic acid, ellagic acid, gallic acid, caffeic acid; catechin, EGCG, quercetin, rutin, numerous minerals, particularly iron, and amino acids A prominent researcher on the medicinal properties of pomegranate, cautions against focusing on ellagic acid standardisation to the exclusion of other therapeutically important pomegranate constituents as there may be potent synergies. Some polyphenols showing promise for depression include dihydromyricetin, amentoflavone, apigenin, chlorogenic acid, curcumin, ferulic acid, hesperidin, rutin, quercetin, naringenin, resveratrol, ellagic acid, nobiletin, anthocyanins and proanthocyanidins. I'll focus on pomegranate's ellagic acid. In humans, ellagic acid prevents cognitive deficits through normalisation of lipid metabolism, increase in plasma BDNF level, and reduction of saliva cortisol concentration. It may be a useful memory restorative agent and ellagic acid may be used in functional foods or medicines to help treat CNS dysfunction, neurodegenerative disease and aging. Dietary pomegranate produces brain antiinflammatory effects that may attenuate disease progression. Acute and chronic administration of ellagic acid to mice has produced antianxiety-like effect through an involvement of GABAergic system. Ellagic acid may be a natural selective estrogen receptor modulator (SERM). Ellagic acid displays neuroprotective properties against oxidative and inflammatory damages after brain injury. It can improve brain injury outcomes and increase the proliferation of neural stem cells through the Wnt/β-catenin signaling pathway. In models of brain injury, it can restore neurological symptom severity, cognitive and LTP deficits and prevent brain inflammation may by restore BBB permeability as well as lowering brain content of TNF-α. Through it's actions on myelination, it is a suitable therapeutic agent for moderate brain damage in neurodegenerative diseases such as multiple sclerosis. It has other neuroprotective potential in Parkinson's via amelioration of apoptosis and oxidative stress, suppression of MAO-B, and its favorable influence is partly reliant on ERβ/Nrf2/HO-1 signaling cascade. In models of cognitive decline, it could dose-dependently improve learning and memory deficits via neuronal protection and at molecular level through mitigation of oxidative stress and acetylcholinesterase (AChE) activity and modulation of NF-κB/Nrf2/TLR4 signaling pathway. Other potential applications include brain ischemia, male infertility, Alzheimer's disease, arthritis, and obesity.

@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

Starting to see even more common 'ornamental' plants as medicines... even the Salvias I wrote off as uninteresting. A trip to look at plants or even just wandering the streets is like visiting 'The Creator's Pharmacy'... trying to work out the medicine of the Salvia plants I discounted that grow around the garden and nearby. Some I cherish, from my Salvia officinalis which I try to use quite often as a functional food healing tonic, to my Clary sage, which I use as essential oil and have nibbled a few leaves off, to my Pineapple Sage which is antidepressive, anxiolytic and has beneficial effects on blood pressure. This plant, "mirto", is a shrub that has been widely used in Mexican traditional medicine for the treatment of different central nervous system (CNS) diseases, principally, anxiety. These have antidepressant and anxiolytic activity, contain ursolic acid an antidepressant flavanone, 5-O-(6-rhamnosylglucoside)-7-hydroxy-4'-methoxyflavanone. It also has anti-hypertensive activity. Many have pro-cognitive and very useful all round effects, Salvia officinalis and Spanish Sage are good examples. S. officinalis has anticancer, anti-inflammatory, antinociceptive, antioxidant, antimicrobial, antimutagenic, antidementia, hypoglycemic, and hypolipidemic effects [1] Interestingly, one I've seen around, is Salvia guaranitica. From what I hear, "Salvia Guaranitica is certainly active. Contains Cirsiliol. Works noticeably well..." Interested in adding that. Quite available. This plant is used as a traditional medicinal plant used in Latin America as sedative. Studies demonstrated the presence of cirsiliol in its extracts and found that this flavonoid is a competitive low affinity benzodiazepine receptor ligand (Marder et al., 1996). Studies have investigated the pharmacological properties of Salvia guaranitica extracts and of its active principle, cirsiliol. A partially purified fraction of this plant, administered intraperitoneally in mice (in a dose equivalent to 3 g of the fresh plant), exhibited sedative and hypnotic effects as measured in the hole board and in the pentobarbital-induced sleep tests, respectively. Salvia guaranitica extracts and its active principle cirsiliol, possess sedative and hypnotic properties; cirsiliol produces these effects probably acting on the benzodiazepine receptor. Definitely sounds like a good addition. I tried the Salvia splendens 'Blaze of Fire', it seems like a potentially medicinally useful plant - the aerial parts of these plants contain flavonoids, triterpenoids, and monoterpenes, particularly in the flowers and leaves, while diterpenoids are found mostly in the roots. It's a good source of phenolics and has hypoglycemic and antiinflammatory activities along antioxidant effects. Salvia splendens is widely used in Indian traditional medicine for the control of diabetes mellitus. Interestingly, it's also a flower anthocyanin source - derivatives of pelargonidin, delphinidin, or malvidin were isolated. One I think may be Salvia argentea which shows the presence of many chemical groups which possess interesting biological activities. It may find use as an anti-inflammatory. Recently a friend pointed out Salvia dorisiana at the Botanic Gardens, I can't find any literature on the medicinal use of that one but it's culinary uses are there - uses for Fruity Sage include using the leaves and flowers in salads, fruits salads, iced teas and fruit punches. It smells wonderful. While potentially less common and more renowned for it's medicine, the Clary Sage is quite interesting. S. sclarea extract had decent affinity for the 5-HT2A receptors and fairly good affinity for the D2 receptors. Clary sage oil has antidepressant-like effects and potent anti-stress effects, I find it better than Lavender. The antidepressant-like effect of clary oil is closely associated with modulation of the DAergic pathway while the anti-stress effect relies on DA/5-HT1A pathways. There's a thread on other Salvias here.

I've written some stuff on Magnolia, Aptenia and Coleus. Please do not use these plants medicinally unless you are skilled and aware of potential risks. Vinca Garden was overrun by Vinca minor, Had to do some removal so I did a full spectrum root and leaf ethanol extract and came up with a black tar last year. I have had interesting effects from bits of the root. It has potential nootropic activity through alkaloids like vincamine. Vincamine is a plant alkaloid used clinically as a peripheral vasodilator that increases cerebral blood flow and oxygen and glucose utilisation by neural tissue to combat the effect of aging. To make a cup of Periwinkle tea, you will need a teaspoon of dried periwinkle leaves. Pour the leaves into a cup full of boiling water and let it steep for 5-10 minutes. Once steeping is done, strain to remove the herbs. After staining your cup of the healthy periwinkle, tea is done. Most people find the tea too bitter. You can sweeten it by adding honey or fruit juice or even Stevia. Did 1g of the root with some leaves, bitter as anything but drinkable. Supposedly a mild euphoriant, hypnotic tranquiliser, anxiolytic It's got quite a bit of symbolism, the Virgin Mary, love and death. "V. minor contains monomeric eburnamine-type indole alkaloids including vincamine which has modulatory effects on brain circulation and neuronal homeostasis as well as antihypoxic and neuroprotective potencies. Vincamine is used for the prevention and treatment of cerebrovascular insufficiencies and disorders. A large body of clinical evidence indicates a favorable effect of vincamine in a number of brain disorders of elderly patients, such as memory disturbances, vertigo, transient ischemic deficits, and headache. It increases cerebral blood flow, oxygen consumption and glucose utilisation. In general, Vinca minor is known to be a valuable medicinal plant. Different parameters including climate and soil requirements, agricultural measures such as propagation, planting, fertilisation and harvest date vastly influence the quality of plant material and alkaloid concentration. It has been shown that nitrogenous fertilizers significantly increase the content of alkaloids. Besides, the content of alkaloids reaches its maximum at the flowering stage Five indole alkaloids including vincaminorine, vincaminoreine, minovine, minovincine, and vincamine were isolated from the aerial parts of V. minor. Vincamine was found to be the dominant alkaloid in this plant with the content of 0.057% of the dried plant mass." [1] Catharanthus roseus - Medicinal Potted Colour While this plant may be merely making itself around as potted colour to some, I frankly get annoyed at those who get locked in at aesthetics in their gardens - it's a welcome addition to my garden, going well with my Vinca minor which is rich in brain nutrition. In Ayurveda (Indian traditional medicine) the extracts of its roots and shoots, though poisonous, are used against several diseases. In traditional Chinese medicine, extracts from it have been used against numerous diseases, including diabetes, malaria, and Hodgkin's lymphoma. Many of the vinca alkaloids were first isolated from Catharanthus roseus, including vinblastine and vincristine used in the treatment of leukemia and Hodgkin's lymphoma. It is rich in monoterpene indole alkaloids - Catharanthus roseus is noted for its array of dozens of alkaloids, including alstonine, reserpine, vinblastine, vincristine, yohimbine,and others of yohimbinoid and strychnoidbases It decreases blood pressure and reduces excitement (containing reserpine). It has anti-diabetic activity Strelitzia reginae "Bird of Paradise" You can please everyone aesthetically and use it medicinally. It's not just a pretty ornamental. You get a mixture of healing anthocyanins from the flowers and other polyphenols in the whole plant. There are some very debatable speculative rumors on psychoactivity but I can't find any references. The abakwaMthethwa clan in KwaZulu-Natal use the strained decoctions from the inflorence to treat inflammation and venereal diseases. Delphinidin-3-rutinoside has been isolated from the petals and proanthocyanidin polymers, flavonoids (antioxidants and on the whole beneficial healing substances) from the leaves. Leaves of this genus are listed as ‘possibly toxic' to animals so caution is needed. The seeds are supposedly more toxic and will cause vomiting if ingested. The rhizome contains phenalenones, these lack understanding of their therapeutic potential. Rose I had a beautiful experience of being drawn to, physically, olfactorily, emotionally, spiritually connecting to a white rose on a long walk. Merging with it's spirit. Learning the medicine of an open heart and how I need to embody that more in my life. Before, I would have never called a rose a medicine. "Rose petals and their medicine help to move and open a heart which has tightened emotionally and spiritually. In both Traditional Chinese Medicine (TCM) and the Unani (Greek-Arabic medicine) traditions, the heart is believed to be a physical organ and the seat of consciousness. TCM uses the term shen, while Unani medicine talks about pneuma. Both schools teach that rose has a powerful affect on the spiritual state of one’s heart. Unani medicine has a category of heart herbs termed as “exhilarants”, which help the spiritual heart feel joy. Rose is considered both a shen tonic in TCM and an exhilarant in Unani medicine. A wonderful nervine, great for uplifting the mood and alleviating depression, rose also has antispasmodic, aphrodisiac and sedative qualities, as well as being anti-inflammatory. Rose helps regulate menstruation as well as stimulate the digestion. Rosehips, which come along after the bloom has faded, are a wonderful source of vitamins C, B2 and E."

Interesting recent results with berries, particularly looking at high anthocyanin berries. Aronia contains a variety of ingredients such as polyphenols, anthocyanins, flavonoids, and tannins. Especially, anthocyanin content in aronia berry is known to be much higher than in other plants and berries. It is known for exerting antioxidant, anti-inflammation, and anti-aging effects. Such a strategy may be tasty and useful Other anthocyanins seem to help, too. Anthocyanins from black carrot were found to be effective to control diabetes Things like tart cherry have a strong biochemical basis for management of type 2 diabetes and cardiovascular disease by controlling glucose absorption, reducing associated hypertension and inflammation.

Cool new papers. Ever wondered what the symbiotic funkiness of Convolvulaceae looked like? In this pic: The fungus/plant symbioses Periglandula/Ipomoea or Periglandula/Turbina: flowers of the host plant I. asarifolia (A), I. asarifolia (red blooming) (B), T. corymbosa (C); epiphytic colonization of a young leaf of T. corymbosa by P. turbinae forming typical mycelium mats along the veins (D, E); ergoline alkaloids visualized by their UV-auto fluorescence within the mycelium of a young colony of P. ipomoeae (F); a peltate glandular trichome (pgt) encircled by hyphae of P. ipomoeae forming the interface of the symbiotum (G); formation of an appressorium-like structure (ap) on the cuticle of the secretory cell of the glandular trichome indicating the close contact of fungus and plant in the symbiosis (H); hyphae (hy) of P. ipomoeae embedded in the matrix (m) of subcuticular space of the peltate glandular trichome (pgt) (I). Ref: http://www.thieme-connect.com/DOI/DOI?10.1055/a-0577-8049 Full text: http://sci-hub.tw/10.1055/a-0577-8049 There's also a Dark Classics in Chemical Neuroscience on the synthetic analogue of potential therapeutic relevance to people: https://dx.doi.org/10.1021/acschemneuro.8b00043 (Full text: http://sci-hub.tw/…//dx.doi.org/10.1021/acschemneuro.8b00043)

@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]