• Members of the previous forum can retrieve their temporary password here, (login and check your PM).

Acetylcholinesterase inhibitors from three common lillys...

Migrated topic.

MaNoMaNoM

Rising Star
Hello Folks, i wanted to compile some info i gathered so far about these plants..
The goal is to safely extract and purify, galanthamine/sanguinine type alkaloids.

From a post about lucid dreaming.... someone mentioned this...
post on extracting Galantamine from snowdrops and daffodils.


There are hundreds of these growing around my house....
(they are also very cheap to buy, several bulbs cost 1$)
707px-Narcissus_pseudonarcissus_flower_300303.jpg

Narcissus Pseudo-narcissus 'the common wild daffodil'

Toxicity
Pharmacology
(SOURCE)
All Narcissus species contain the alkaloid poison lycorine, mostly in the bulb but also in the leaves.[172] Members of the monocot subfamily Amaryllidoideae present a unique type of alkaloids, the norbelladine alkaloids, which are 4-methylcatechol derivatives combined with tyrosine. They are responsible for the poisonous properties of a number of the species. Over 200 different chemical structures of these compounds are known, of which 79 or more are known from Narcissus alone.[173]

The toxic effects of ingesting Narcissus products for both man and animals (such as cattle, goats, pigs and cats) have long been recognised and they have been used in suicide attempts. Ingestion of N. pseudonarcissus or N. jonquilla is followed by salivation, acute abdominal pains, nausea, vomiting, and diarrhea, then neurological and cardiac events, including trembling, convulsions, and paralysis. Death may result if large quantities are consumed.

The toxicity of Narcissus varies with species, N. poeticus being more toxic than N. pseudonarcissus, for instance. The distribution of toxins within the plant also varies, for instance there is a five times higher concentration of alkaloid in the stem of N. papyraceus than in the bulb, making it dangerous to herbivores more likely to consume the stem than the bulb, and is part of the plant's defence mechanisms. The distribution of alkaloids within tissues may also reflect defence against parasites.[18] The bulbs can also be toxic to other nearby plants, including roses, rice, and cabbages, inhibiting growth.[18] For instance placing cut flowers in a vase alongside other flowers shortens the life of the latter.[174]
Poisoning

Many cases of poisoning or death have occurred when narcissi bulbs have been mistaken for leeks or onions and cooked and eaten. Recovery is usually complete in a few hours without any specific intervention. In more severe cases involving ingestion of large quantities of bulbs activated charcoal, salts, and laxatives may be required, and for severe symptoms intravenous atropine and emetics or stomach pumping may be indicated. However, ingestion of large quantities accidentally is unusual because of a strong unpleasant taste. When narcissi were compared with a number of other plants not normally consumed by animals, narcissi were the most repellant, specifically N. pseudonarcissus Consequently narcissus alkaloids have been used as repellents and may also discourage fungi, molds, and bacteria.[18]

On 1 May 2009 a number of schoolchildren fell ill at Gorseland Primary School in Martlesham Heath, Suffolk, England, after a daffodil bulb was added to soup during a cookery class.[172]
Topical effects

One of the most common dermatitis problems for flower pickers, packers, florists and gardeners, "daffodil itch", involves dryness, fissures, scaling, and erythema in the hands, often accompanied by subungual hyperkeratosis (thickening of the skin beneath the nails). It is blamed on exposure to calcium oxalate, chelidonic acid or alkaloids such as lycorine in the sap, either due to a direct irritant effect or an allergic reaction.[175][176] It has long been recognised that some cultivars provoke dermatitis more readily than others. N. pseudonarcissus and the cultivars 'Actaea', 'Camparelle', 'Gloriosa', 'Grande Monarque', 'Ornatus', 'Princeps' and 'Scilly White' are known to do so.[18][177]

If bulb extracts come into contact with wounds, both central nervous system and cardiac symptoms may result. The scent can also cause toxic reactions such as headaches and vomiting from N. bulbocodium.[18]

Topical effects

One of the most common dermatitis problems for flower pickers, packers, florists and gardeners, "daffodil itch", involves dryness, fissures, scaling, and erythema in the hands, often accompanied by subungual hyperkeratosis (thickening of the skin beneath the nails). It is blamed on exposure to calcium oxalate, chelidonic acid or alkaloids such as lycorine in the sap, either due to a direct irritant effect or an allergic reaction.[175][176] It has long been recognised that some cultivars provoke dermatitis more readily than others. N. pseudonarcissus and the cultivars 'Actaea', 'Camparelle', 'Gloriosa', 'Grande Monarque', 'Ornatus', 'Princeps' and 'Scilly White' are known to do so.[18][177]

If bulb extracts come into contact with wounds, both central nervous system and cardiac symptoms may result. The scent can also cause toxic reactions such as headaches and vomiting from N. bulbocodium.[18]
Uses
Traditional medicine

Despite the lethal potential of Narcissus alkaloids, they have been used for centuries as traditional medicines for a variety of complaints, including cancer. N. poeticus is described in the Bible in the treatment of cancer.[174] In the Classical Greek world Hippocrates (ca. B.C. 460–370) recommended a pessary prepared from narcissus oil for uterine tumors, a practice continued by Pedanius Dioscorides (ca. A.D. 40–90) and Soranus of Ephesus (A.D. 98–138) in the first and second centuries A.D., while the Roman Pliny the Elder (A.D. 23–79), advocated topical use.[174] The bulbs of N. poeticus contain the antineoplastic agent narciclasine. This usage is also found in later Arabian, North African, Central American and Chinese medicine during the Middle Ages.[174] In China N. tazetta var. chinensis was grown as an ornamental plant but the bulbs were applied topically to tumors in traditional folk medicine. These bulbs contain pretazettine, an active antitumor compound.[18][178][179]

Narcissus products have received a variety of other uses. The Roman physician Aulus Cornelius Celsus listed narcissus root in De Medicina among medical herbs, described as emollient, erodent, and "powerful to disperse whatever has collected in any part of the body". N. tazetta bulbs were used in Turkey as a remedy for abscesses in the belief they were antiphlogistic and analgesic. Other uses include the application to wounds, strains, painful joints and various local ailments as an ointment called ‘Narcissimum’. Powdered flowers have also been used medically, as an emetic, a decongestant and for the relief of dysentery, in the form of a syrup or infusion. The French used the flowers as an antispasmodic, the Arabs the oil for baldness and also an aphrodisiac. In the eighteenth century the Irish herbal of John K’Eogh recommended pounding the roots in honey for use on burns, bruises, dislocations and freckles, and for drawing out thorns and splinters. N. tazetta bulbs have also been used for contraception, while the flowers have been recommended for hysteria and epilepsy. A homeopathic medicine made from bulbs was prescribed for bronchitis and whooping cough.[18] In the traditional Japanese medicine of kampo, wounds were treated with narcissus root and wheat flour paste;[180] the plant, however, does not appear in the modern kampo herb list.

There is also a long history of the use of Narcissus as a stimulant and to induce trance like states and hallucinations. Sophocles referred to the narcissus as the ‘Chaplet of the infernal Gods’,[65] a statement frequently wrongly attributed to Socrates (see Antiquity).[18]
Biological properties

Extracts of Narcissus have demonstrated a number of potentially useful biological properties including antiviral, prophage induction, antibacterial, antifungal, antimalarial, insecticidal, cytotoxic, antitumor, antimitotic, antiplatelet, hypotensive, emetic, acetylcholine esterase inhibitory, antifertility, antinociceptive, chronotropic, pheromone, plant growth inhibitor, and allelopathic.[18] An ethanol extract of Narcissus bulbs was found effective in one mouse model of nociception, para-benzoquinone induced abdominal constriction, but not in another, the hot plate test.[181] Most of these properties are due to alkaloids, but some are also due to mannosa-binding lectins. The most-studied alkaloids in this group are galantamine, lycorine, narciclasine, and pretazettine.

It is likely that the traditional use of narcissi for the treatment of cancer was due to the presence of isocarbostyril constituents such as narciclasine, pancratistatin and their congeners. N. poeticus contains about 0.12g of narciclasine per kg of fresh bulbs.[174]

Acetylcholine esterase inhibition has attracted the most interest as a possible therapeutic intervention, with activity varying by a thousandfold between species, and the greatest activity seen in those that contain galantamine or epinorgalanthamine.[56]

The rodent repellant properties of Narcissus alkaloids have been utilised in horticulture to protect more vulnerable bulbs.

Galantamine a 'Acetylcholinesterase inhibitor', is said to greatly increase lucid dreaming.
Also used in treating Alzheimer's disease, and in expensive skin creams, and other things..
(Daffodils are big in cancer research, and are the emblem of several cancer organizations.)
Galantamine can be bought online in pill or powder, but iam interested in making extracts.

Two of the main alkaloids in daffodils are Galantamine, and the poisonous Lycorine.
i believe the lycorine is the center of the cancer research. (Medicines from Poison!)

Lycorine is the major active component from the amaryllidaceae family plant Lycoris radiate, a represent traditional Chinese medicinal herb, and is one of the typical alkaloids with pyrrolophenanthridine nucleus core. Lycorine has drawn great interest in medicinal field due to its divergent chemical structures and multiple biological functions, as well as pharmacological effects on various diseases. Accumulated evidence shows that lycorine not only possesses strong pharmacological effects on many diseases, including anti-leukemia, anti-tumor, anti-angiogenesis, anti-virus, anti-bacteria, anti-inflammation, and antimalaria, but also exerts many other biological functions, such as inhibition of acetylcholinesterase and topoisomerase, suppression of ascorbic acid biosynthesis, and control of circadian period length. Notably, lycorine exhibits its numerous pharmacological effects on various diseases with very low toxicity and mild side effects. The divergent chemical structures, multiple biological functions, and very low toxicity of lycorine imply that the agent is a potential drug candidate that warrants for further preclinical and clinic investigation. (SOURCE)

Ever seem like something is trying to tell you something?

Leucojum aestivum sub. pulchelum 'summer snowflake'
Leucojum_aestivum_var_pulchellum_JAY.jpg

i'd find this plant all the time, and always been thinking, hmmm you hold magic!
Now, i know what magic it holds, and hope to extract it, for safe experimenting.

Sanguinine (272), reported as a constituent of Leucojum aestivum sub. was obtained from Leucojum aestivum sub. pulchelum (SANGUININE on PUBMED)

i cannot find the source but read somewhere;
-Sanguinine is a 10X more potent acetylcholinesterase inhibitor than galanthamine.

Abstract
(SOURCE)

Amaryllidaceous plants produce pharmacologically active alkaloids, galanthamine being the most interesting for its use in the treatment of Alzheimer's disease as a cholinesterase inhibitor. The aim of this work was to test 23 pure Amaryllidaceae alkaloids and 26 extracts from different species of the genus Narcissus for their acetylcholinesterase inhibitory activity using galanthamine as a reference. Only seven alkaloids, belonging to the galanthamine and lycorine skeleton types, exhibited such an effect, sanguinine being the most active, even more than galanthamine. All the extracts with the highest acetylcholinesterase inhibitory activity contained galanthamine except that of N. assoanus, a lycorine type alkaloid-bearing species.

Leucojum aestivum sub. pulchellum

Abstract (SOURCE)

Leucojum aestivum (summer snowflake) is a plant species used for the extraction of galanthamine, an acetylcholinesterase inhibitor for the treatment of Alzheimer's disease. Extracts from bulbs collected from 18 Bulgarian populations and from shoot-clumps obtained in vitro from 8 different populations showed variations in their alkaloid composition. Nineteen alkaloids were detected in the studied samples by GC-MS. Typically, the alkaloid fractions of L. aestivum bulbs were dominated by galanthamine type compounds, but lycorine, haemanthamine and homolycorine type alkaloids were also found as dominant compounds in some of the samples. Extracts from the shoot-clumps obtained in vitro were found to contain galanthamine or lycorine as main alkaloids. The galanthamine content ranged from 28 to 2104 microg/g dry weight in the bulbs, and from traces to 454 microg/g dry weight in the shoot-clumps.

Abstract (SOURCE)

The alkaloids of intact plants, calli and shoot-clump cultures of L. aestivum were analyzed by GC-MS. Twenty-four alkaloids were detected. Calli appeared to produce sparse alkaloid profiles in stark contrast to shoot-clumps that had similar profiles to those of the intact plant. Seven shoot-clump strains produced galanthamine predominantly whereas another three were dominated by lycorine. Shoot-clump strains cultivated under light accumulated about two-times more galanthamine (an average of 74 microg/g of dry weight) than those cultivated in darkness (an average of 39 microg/g of dry weight). In comparison to intact plants, the shoot-clumps accumulated 5-times less galanthamine. The high variability of both the galanthamine content (67% and 75% of coefficient of variation under light and darkness conditions, respectively) and alkaloid patterns indicates that the shoot-clump cultures initiated from callus could be used as a tool for improvement of the in vitro cultures.

Optimized nutrient medium for galanthamine production in Leucojum aestivum L. in vitro shoot system.
Abstract (SOURCE)

The common effect of NH4+, NO3-, KH2PO4 and sucrose on the biosynthesis of galanthamine by a Leucojum aestivum shoot culture was studied. Polynominal regression models were elaborated for the description of the galanthamine biosynthesis as a consequence of variation of the investigated variables (NH4+ between 0.20 and 0.54 g/L; NO3- between 1.44 and 3.44 g/L; KH2PO4 between 0.10 and 0.24 g/L, and sucrose between 30.00 and 60.00 g/L). Optimization procedures allowed us to establish the optimal concentrations of the investigated variables and to propose the modified MS nutrient medium, with 4.50 g/L KNO3, 0.89 g/L NH4NO3, 1.25 g/L (NH4)2SO4, 0.10 g/L KH2PO4 and 60 g/L sucrose, for the galanthamine production by a Leucojum aestivum shoot culture. The proposed modified MS medium provided considerable increase of both the production yield and the relative content of the target alkaloid in the alkaloid mixture.

And finally, the red spider lily, AKA the magic lily,(Lycoris radiata) These pop-up everywhere, usually in the early fall.
800px-Higanbana_in_a_woods.jpg



Today, it is used commercially as an extract derived from red spider lily (Lycoris radiata), the Golden spider lily (Lycoris aurea) or from the Snowdrop plant (Galanthus nivalis). The resulting compound is galanthamine hydrobromide.
(SOURCE)


:x DISCLAIMER; These plants DO CONTAIN TOXINS. Please be 100% safe!
Next we look at the extraction process, and would appreciate any help. :?
 
Here is another interesting one; The common DayLily, Hemerocallis Spp.

dscf0476.jpg


"Large quantities of the leaves are said to be hallucinogenic."
Blanching the leaves removes this hallucinatory component[205].

Leaves /young shoots cooked as asparagus /celery substitute.
An excellent sweet tasting vegetable[179, K], though some caution is recommended[127, 137].

The dried flower contains about 9.3% protein. 25% fat!?, 60% carbohydrate (rich in sugar), 0.9% ash. rich in vitamin A[179]. Tubers - raw or cooked[183]. A nutty flavour[62]. Young tubers are best, though the central portion of older tubers is also good[85].

Medicinal Uses

Anodyne; Anthelmintic; Antidote; Antiemetic; Antispasmodic;
Blood purifier; Cancer; Depurative; Diuretic; Febrifuge; Laxative; Sedative.

The flowers are very safe, antiemetic, antispasmodic, depurative, febrifuge and sedative[218]. In China they are used as an anodyne for women in childbirth.

[240]. An extract of the flowers is used as a blood purifier[240].
The rhizome has shown antimicrobial acivity, it is also tuberculostatic and has an action against the parasitic worms that cause filariasis[279].

It is used in Korea to treat oppilation, jaundice, constipation and pneumonia[279].

The juice of the roots is an effective antidote in cases of arsenic poisoning[205].

The root also has a folk history of use in the treatment of cancer -
extracts from the roots have shown antitumour activity[218].

A tea made from the boiled roots is used as a diuretic[205, 218].

Other Uses
Weaving.

SOURCE

Daylily (Hemerocallis spp.) flowers are utilized as an important ingredient in traditional Asian cuisine and are also valued for their reputed medicinal effects. In studies of the bioactive methanol and aqueous methanol extracts of lyophilized Hemerocallis cv. Stella de Oro flowers, kaempferol, quercetin, and isorhamnetin 3-O-glycosides (1−9), phenethyl β-d-glucopyranoside (10), orcinol β-d-glucopyranoside (11), phloretin 2‘-O-β-d-glucopyranoside (12), phloretin 2‘-O-β-d-xylopyranosyl-(1→6)-β-d-glucopyranoside (13), a new naphthalene glycoside, stelladerol (14), and an amino acid (longitubanine A) (15) have been isolated. All of these compounds were tested for their antioxidant and cyclooxygenase inhibitory activities. Stelladerol was found to possess strong antioxidant properties, inhibiting lipid oxidation by 94.6% ± 1.4 at 10 μM in an in vitro assay. Several of the flavonol 3-O-glycoside isolates also demonstrated modest antioxidant activities at 10 μM. None of the isolates inhibited cyclooxygenase activity at 100 μM.

SOURCE

THE GENUS HEMEROCALLIS ANTIDEPRESSANT-LIKE EFFECTS OR FATIGUE-RELIEVING EFFECTS BASED ON SLEEP IMPROVEMENT SOURCE

Results

The antidepressant-like effects of hydroalcoholic H. citrina extracts were mainly related to flavonoids, especially rutin and hesperidin. The extract prepared using 75% ethanol (i.e., HCE75) exhibited the highest active flavonoid content and activity. Orally administered 400 mg/kg of HCE75 significantly induced an antidepressant-like effect, whereas the combination of equivalent rutin and hesperidin dosages exhibited the same profiles. Isobologram analysis showed sub-additive antidepressant interactions between rutin and hesperidin. HCE75 (400 mg/kg, p.o.) increased the serotonin and dopamine levels in the central nervous system. Mortality and lesions were not observed upon oral administration of up to 5000 mg/kg HCE75.

Conclusions

The antidepressant-like effects of hydroalcoholic H. citrina extracts are mainly related to flavonoids, especially rutin and hesperidin. The serotonergic and dopaminergic systems may have major roles. The active extract is toxicologically safe for oral administration.

SOURCE

The roots contains swertiamarin, laganin, picraquassioside C, puerarin, 3-methoxylpuerarin, 7-hydroxylnaphthalide-O-β-D- glucopyranoside, 3,5-dihydroxytoluene-3-O-β-D- glucopyranoside, HN saponin F, hederagenin-3-O-β-D- glucopyranosyl-(1→3)-α-L-arabinopyranosyl-28-O-β-D-glucopyranosyl-ester[1];3α-acetyl-11-oxo-12-ursen-24-carboxylicacid, 3-oxo-lanosta-8,24-diene-21-carboxylicacid, 3β-hydroxlanosta-8,24-diene-21-carboxylic acid, 3α-hydroxlanosta-8,24-diene-21-carboxylicacid, 25R- spirostan-4-ene-3,12-dione, 2′,4,6′- trihydroxy-4′-methoxyl-3′-methyl-dihydroxy chalcone, α-boswellicacid, β-boswellic acid, 11α-hydroxy-3-acetyl-β-boswellicacid[2];Chrysophanol, hemerocal, 2-methoxyobtusifolin, obtusifolin, emodin, aloe-emodin, rhein[3]; pigment, chrysophanol, rhein, 1,8-dihydroxy-2-acetyl-3-methylnaphthalene, asparagines, mihemerocallin, hemerocallin, heptacosane, hemerocallone, β-sitosterol, γ-sitosterol[3];The whole plant also contains hemerocallin[3].
1.Antibacterial:Emodin, aloe-emodin was inhibited by Staphylococcus aureus,Escherichia coli,Shigella bacillus, but Aloe emodin produce drug resistance[1].Mechanismsis that emodin, rhein, aloe the rhubarb cable can inhibitmitochondrialrespiratory chain electron transport of bacterial cells, and affect tissue cellular activities required for the supply of energy. Chrysophanol,physcionthe biological activity is not strong, but in the body may beconverted toemodin, rhein play the pharmacological effects[2]. The root andetherextract have a therapeutic effect on tuberculosis in guinea pigs[3,4].
2.Antischistosomals:Rootcan play the effect on schistosomiasis of the experimental treatment, buttheresults are quite inconsistent in units report. As hemerocallin hasstrongtoxicity to the host, and the safe range is small, there is noclinicalvalue[3,5].
3.Sedation: Orange DaylilyRoot has asignificant sedation [8].
4.Diuretic: It hasThe diuretic effect on the different diseases caused by swellingdiuretic, but morepronounced renal edema[4].
5.Anti-tumor:Emodin can significantly inhibit on DNA biosynthesis of A-549 lungcancer cell[9].Colchicine can significantly inhibit on cell mitosis, which has been used to treat breast cancer, skin cancer, and leukemia in clinical[10]
6.Inhibitionofvascular smooth muscle cell proliferation: Emodin can inhibit vascularsmoothmuscle cell proliferation[11]. Inhibition of the migration ofPCNAprotein expression and blocking the cell cycle, which is maybe one oftheimportant mechanism of emodin inhibition vascular smooth musclecellproliferation[12].
7.Diuretic:Chrysophanol and rhein have diuretic effect[13]. Emodin caninhibitmesangial cell
proliferation, and inhibit mesangial cells the autocrineor sidethe glomerular to secret interleukin-1, interleukin-6, tumor necrosisfactorand other local inflammatory[14].
8.On therole ofthe immune system: Rhein, emodin and aloe emodin has different degreesofinhibition on mice immune system, such as reducing the weight of immuneorgans,and the generation of anti-Hugh, white blood cell count, and inhibitingthecarbon clearance functional and peritoneal macrophages to phagocytosis[15].
9.Liver: Emodinhassignificant protective effect on hepatocytes of primary cultured rat causedbycarbon tetrachloride (CCl4), and emodin has a therapeutic effect onhepaticfibrosis in rats[16].
10.Insecticide:The battalion grass prime is the active ingredient of the Velvetthe Grassrootstreatment of schistosomiasis. However, due to the shortcomingsof its poisonoptic system lead to blindness, not for clinical use[17].

This product is toxic; toxicity is mainly concentrated in the roots. the performance of poison in mice caused brain, spinal cord white matter and optic nerve cellulose of softening and myelin disappearing, generally lighter gray matter lesions of varying degrees of cloudy swelling, liver and kidney cells, lung hemorrhage or plaque hemorrhage; poisoning in dogs and rabbits showed pupil dilated, light reflex, lower limb paralysis and urinary retention to death;poisoning in rabbits caused hemerocallin proteinuria, urine glucose andimpaired glucose tolerance. Toxicity of Orange Daylily Root are very differentbecause of different origin, heated above 60 ℃ can weaken or even destroy the toxicity. Oral administration of Orange Daylily Root caused in vivo accumulation; Coptis, Phellodendron canpartially remove its toxicity [1,2,3].

SOURCE

Orange_Daylily.jpg

Hemerocallis 'Kwanzo' – a triple-flowered triploid cultivar
 
Back
Top Bottom