Hidrastinina

Salvar

La hidrastinina es un alcaloide semisintético de la hidrólisis del

alcaloide hidrastina , que se encontró naturalmente en pequeñas cantidades
en Hydrastis canadensis L. ( Ranunculaceae ). La hidrastinina se produjo
mediante la división oxidativa del hidrocloruro de hidrastina con ácido nítrico
con un buen rendimiento. La droga fue patentada por Bayer como
una droga hemostática durante la década de 1910.
La primera síntesis conocida de metilendioximetanfetamina (MDMA) fue en
realidad un intermedio en la síntesis del análogo metilado de hidrastinina,
metilhidrastinina. Solo fue revisado por su actividad muchos años después de
su síntesis original. [1]
La hidrastinina también se ha encontrado como una impureza o producto
secundario en la síntesis de MDMA realizada por aminación a baja presión de
3,4-metilendioxifenilpropan-2-ona con metilamina. [2]
Referencias

1. Roland W. Freudenmann; Florian Öxler; Sabine Bernschneider-Reif

(2006). "El origen de MDMA (éxtasis) revisitado: la historia real reconstruida
a partir de los documentos originales" (PDF) . Adiccion. 101 (9): 1241-
5. doi : 10.1111 / j.1360-0443.2006.01511.x . PMID 16911722 .
2. Verweij, AM (1991). "Contaminación de anfetaminas ilegales. Hidrastatinina
como contaminante en 3,4- (metilendioxi) metilanfetamina". Archiv für
Kriminologie. 188 (1-2): 54-7. PMID 1953248 .

Hidrastina

Salvar
La hidrastina es un alcaloide que fue descubierto en 1851 por Alfred P.
Durand. [1] La hidrólisis de hidrastina produce hidrastinina , que fue patentada
por Bayer como un fármaco hemostático [2] durante la década de 1910. Está
presente en Hydrastis canadensis (por lo tanto, el nombre) y otras plantas de
la familia Ranunculaceae .
Síntesis total
El primer intento para la síntesis total de hidrastina fue informado por Sir Robert
Robinson y colaboradores [3] en 1931. Después de los estudios [4] [5] donde la
síntesis de la amida lactónica clave intermedia (estructura 4 en la figura) fue la
Lo más problemático fue que el mayor avance se logró en 1981 cuando JR
Falck y colaboradores [6] informaron una síntesis total de cuatro etapas de
hidrastina a partir de materiales de partida simples. El paso clave en la síntesis
de Flack fue el uso de una reacción de Passerini para construir el intermediario
amida lactónica 4.
A partir de una variante simple de bromuro de fenilo 1, la reacción de
alquilación con metilisocianuro de litio da el isocianuro intermedio 2. La
reacción del isocianuro intermedio 2 con ácido opiánico 3 inició la reacción
intramusular de Passerini para dar la amida lactónica intermediaria 4. El anillo
de tetrahidroisoquinolina se formó por primera vez una reacción de cierre de
anillo en condiciones de deshidratación usando POCl3 y luego una
hidrogenación catalizada utilizando PtO2 como catalizador. Finalmente, la
hidrastina se sintetizó mediante la instalación del grupo N-metilo a través
de la reacción de aminación reductiva con formaldehído .
Referencias

1. Pharmaceutical Journal ;: Un registro semanal de Farmacia y Ciencias

Afines . J. Churchill. 1862. pp. 547-.
2. Römpp CD, Georg Thieme Verlag, 2006
3. Hope, Edward; Pyman, Frank Lee; Remfry, Frederick George
Percy; Robinson, Robert (1931). "XXXI.-Una síntesis de hidrastina. Parte
I". J. Chem. Soc. 0 (0): 236-247. doi : 10.1039 /
JR9310000236 . ISSN 0368-1769 .
 4. Haworth, RD; Pinder, AR; Robinson, R. (1950). "Síntesis de
Hydrastine". Naturaleza. 165 (4196): 529-529. doi : 10.1038 /
165529a0 . ISSN 0028-0836 .
5. Haworth, Robert D .; Pinder, A. Reginald (1950). "360. Una nueva ruta a
las bases de ftalida-isoquinolina, y una síntesis de (-) - hidrastina". J.
Chem. Soc. 0 (0): 1776-1780. doi : 10.1039 / JR9500001776 . ISSN 0368-
1769 .
6. Falck, JR; Manna, Sukumar (1981). "Una reacción de passerini
intramolecular: Síntesis de hidrastina". Letras de Tetrahedron. 22 (7): 619-
620. doi : 10.1016 / S0040-4039 (01) 92504-3 . ISSN 0040-4039 .

enlaces externos

 Chisholm, Hugh, ed. (1911) " Hidrastina ". Encyclopædia

Britannica . 14 (11ª ed). Prensa de la Universidad de Cambridge. pag. 34.

Goldenseal

Salvar

El sello de oro ( Hydrastis canadensis ), también

llamado orangeroot [2] o amarilla puccoon , [2] es una planta
perenne herbácea en el botón de oro de la familia Ranunculaceae , nativa del
sudeste de Canadá y el este de los Estados Unidos . Se puede distinguir por
su patrón grueso y amarillo anudado . El tallo es violáceo y peloso por encima
del suelo y amarillo por debajo del suelo, donde se conecta con el rizoma
amarillo. Goldenseal generalmente se reproduce clonalmente a través del
rizoma. [3]La planta tiene dos palmas, hojas peludas con 5-7 lóbulos de dientes
dobles e individuales, flores pequeñas, discretas con estambres de color blanco
verdoso a finales de la primavera. En verano, lleva una sola baya del tamaño
de una frambuesa grande con 10-30 semillas. [4]
En la medicina herbal, las raíces y los rizomas de goldenseal se cosechan y se
usan como un remedio multiuso debido a sus altas concentraciones de
berberina e hidrastina. [5] Se cree que la hierba es antiinflamatoria,
antidiarreica, antibacteriana e inmunoestimulante. [5] Sin embargo, hay poca
evidencia científica de que el sello de oro sea efectivo. [6]Goldenseal se usa
para controlar los espasmos musculares , tratar el cáncer, estimular el corazón
y aumentar la presión arterial, tratar los trastornos gastrointestinales , tratar
la conjuntivitis , controlar la menstruación dolorosa y abundante , tratar las
infecciones de forma tópica, reducir la hinchazón y aliviar
el edema . [7]Goldenseal se puede comprar en ungüento , tableta , forma
de tintura o como un polvo a granel. A menudo se usa para aumentar los
efectos medicinales de otras hierbas con las que se mezcla o formula.
Una segunda especie de Japón , anteriormente catalogada como Hydrastis
palmatum, es lo suficientemente distinta como para que ahora se trate en
un género separado , como Glaucidium palmatum .
Eficacia
Actualmente no hay pruebas suficientes para determinar si goldenseal es eficaz
para cualquier condición. [8] [9] [10] Según la Sociedad Estadounidense del
Cáncer , "la evidencia no respalda las afirmaciones de que el sello de oro es
eficaz para tratar el cáncer u otras enfermedades. El sello de oro puede tener
efectos secundarios tóxicos y las dosis altas pueden causar la
muerte". [11] Aunque no se han realizado suficientes investigaciones para
determinar la eficacia de la planta, algunos experimentos han demostrado que
goldenseal es eficaz para reducir la infección y es útil en la prevención y el
tratamiento de MRSA(Staphylococcus aureus resistente a la
meticilina). [12] [13] [14]
El herborista Paul Bergner investigó la investigación y no ha podido encontrar
informes de casos en los que los niveles de patógenos intestinales se redujeron
después de tomar el sello de oro. [15] Un estudio en el que los hombres
con diarrea inducida por E. coli tenían síntomas reducidos del 42-48% después
de tomar berberina mostró niveles inalterables de bacterias intestinales,
patógenas o no, después de tomar el sello de oro. [dieciséis]
Parece probable que el sello de oro comparta con Mahonia (uva de Oregón)
y Berberis (agracejo) la capacidad de inhibir las bombasresistentes a los
medicamentos MDR de las bacterias.
Uso tradicional
En el momento de la colonización europea de las Américas , el sello de oro se
usaba ampliamente en ciertas tribus de nativos americanos de América del
Norte , como medicina y como material colorante. Benjamin Smith Barton , en
su primera edición de Colecciones para un ensayo sobre una materia médica
de los Estados Unidos (1798), se refiere al uso Cherokee de goldenseal como
tratamiento contra el cáncer. [17] Más tarde, llama la atención sobre sus
propiedades como un tónico amargo y como un lavado local para
la oftalmía . Se convirtió en el favorito de los Eclécticos de la época
de Constantin Raffinesqueen la década de 1830 Tribus también usó el sello de
oro para problemas digestivos, como un lavado de ojos, como diurético y como
un amargo. [5]
El Dr. John Henry Pinkard , conocido "Yarb Doctor" y productor de
medicamentos en Roanoke, Virginia , durante los años 1920 y 1930, tenía una
variedad de remedios que preparaba y vendía en su farmacia y se enviaba a
todo el país. Algunos de los nombres fueron: "Compuesto Hidrastic de Pinkard"
(evidentemente hecho de goldenseal o Hydrastis canadensis), "Linimento de
Pinkard" y "Compuesto Sanguinaria de Pinkard" (hecho
con Sanguinaria ). Muchas de sus pociones se basaban en el conocimiento de
hierbas extraído de las prácticas médicas tradicionales de esclavos y rurales de
Virginia y de los remedios tribales locales.
Herbalists today consider goldenseal an alterative, anti-catarrhal, anti-
inflammatory, antiseptic, astringent, bitter tonic, laxative, anti-diabetic and
muscular stimulant.[18] They discuss the astringent effect it has on mucous
membranes of the upper respiratory tract, the gastrointestinal tract, the bladder,
the rectum (applied topically) and the skin. Goldenseal is very bitter, which
stimulates the appetite and aids digestion, and often stimulates bile
secretion.[19][20][21][22]
Constituents and modern pharmacology
Goldenseal contains the isoquinoline alkaloids hydrastine, berberine,
berberastine, hydrastinine, tetrahydroberberastine, canadine and
canalidine.[23] A related compound, 8-oxotetrahydrothalifendine, was identified
in one study.[24] The United States Pharmacopoeia requires goldenseal sold as
a supplement to have hydrastine concentrations of at least 2% and berberine
concentrations of at least 2.5%.[25] The requirements in Europe are that
hydrastine concentrations be at least 2.5% and that berberine concentrations at
least 3%.[25] The hydrastine concentrations of goldenseal plants range
between 1.5% and 5%, while the berberine concentrations are usually between
0.5% and 4.5%.[5]Goldenseal is harvested for its rhizomes because the
concentrations of hydrastine and berberine in the shoots do not meet these
requirements.[25] Berberine and hydrastine act as quaternary bases and are
poorly soluble in water but freely soluble in alcohol. The herb seems to have
synergistic antibacterial activity over berberine in vitro, possibly as a result
of efflux pump inhibitory activity.[26]
Multiple bacteria and fungi, along with selected protozoa and chlamydia, are
susceptible to berberine in vitro.[27] Berberine alone has weak antibiotic activity
in vitro since many microorganisms actively export it from the cell (although a
whole herb is likely to work on the immune system as well as on attacking the
microbes and hence have a stronger clinical effect than the antibiotic activity
alone would suggest). There is some evidence for other berberine-containing
species synthesizing an efflux pump inhibitor that tends to prevent antibiotic
resistance, a case of solid scientific evidence that the herb is superior to the
isolated active principle.[28] However, it is not yet known whether goldenseal
contains a drug resistance MDR pump inhibitor, although many antimicrobial
herbs do.
Toxicity
 Goldenseal in fruit

California is proposing to list goldenseal root powder as a carcinogen.[29]

A study in which pregnant rats were fed about 47 times the usual human dose
of 26 mg/kg concluded, "Maternal liver weights were increased at ≥6250 ppm,
suggesting possible enzyme induction. There was no definitive evidence of
developmental toxicity in this study."[30]Another study, in which mice were fed
about 300 times the estimated human intake from dietary supplements,
concluded, "Maternal liver weights were increased at greater than 12,500 ppm,
but in the absence of treatment-related histopathological lesions. At the high
dose, definitive evidence of developmental toxicity was limited to a statistically
significant (~8%) reduction in average fetal body weight per litter."[31]
The lethal dose (LD) of berberine for humans is thought to be 27.5 mg/kg.
Berberine is absorbed slowly orally; it achieves peak concentrations in four
hours and takes eight hours to clear[32] Berberine is excreted in the urine and
human studies show evidence that it can be absorbed through the
skin. Pharmacokinetic data is not available for hydrastine or goldenseal root
powder. Berberine in humans can cause blocking of receptors in smooth
muscle, blocking potassium channels in the heart and reducing ventricular
tachycardia, inhibiting intestinal ion secretion and toxin formation in the gut and
increasing bile secretion.[33]
While goldenseal, like all alkaloid-rich herbs including coffee and tobacco,
should be avoided during pregnancy and given to very young children with care,
it appears that goldenseal is unlikely to be toxic in normal doses. Interactions
with drugs with narrow therapeutic windows like warfarin, ciclosporin, protease
inhibitors and cardiac glycosides are potential concerns.
Side effects of goldenseal may include "digestive complaints, nervousness,
depression, constipation, rapid heartbeat, diarrhea, stomach cramps and pain,
mouth ulcers, nausea, seizures, vomiting, and central nervous system
depression. High doses may cause breathing problems, paralysis, and even
death. Long-term use may lead to vitamin B deficiency, hallucinations, and
delirium."[11] In addition, goldenseal may cause brain damage to newborn
babies if given directly or if taken by breastfeeding or pregnant mothers,[8] and
may affect blood pressure unpredictably because it contains several
compounds that have opposite effects on blood pressure.[11]
Cautions
Taking goldenseal over a long period of time can reduce absorption of B
vitamins, but it is cautioned to avoid goldenseal during pregnancy and lactation,
with gastrointestinal inflammation and with pro-inflammatory disorders.[22] A
2011 study found rats fed goldenseal constantly for two years had a greater
tendency to develop tumors.[34]
Goldenseal has been found to have inhibited cytochrome
P450 CYP2D6, CYP3A4 and CYP3A5 activity by approximately 40%, a
statistically and clinically significant reduction.[35] CYP2D6 is a known
metabolizer of many commonly used pharmaceuticals, such
as antidepressants(including all SSRIs except
for fluvoxamine), neuroleptics and codeine.[36]Combining goldenseal with such
medications should be done with caution and under the supervision of a doctor
as it can lead to serious, perhaps fatal, toxicity.[37] Those with a genetic
deficiency in these enzymes are at particular risk.
Use for masking illicit drug use in urine drug tests
Goldenseal became a part of American folklore associated with chemical-
testing errors as a result of pharmacist John Uri Lloyd's 1900 novel Stringtown
on the Pike. In the book, the victim's habit of taking goldenseal in the form
of digestive bitters causes the herb to appear as the poison strychnine in a
chemical test, thus suggesting murder.
Goldenseal has been unsuccessfully used in recent years in attemptsqq to
mask the use of morphine in race horses.[38]
Two studies have failed to demonstrate any effect of oral goldenseal on urine
drug assays over water alone.[39] Subjects who drank large amounts of water
had the same urine drug levels as subjects who took goldenseal capsules along
with the water.
Endangered status
Goldenseal became popular in the mid-nineteenth century. By 1905, the herb
was much less plentiful because of overharvesting and habitat destruction. Wild
goldenseal is listed in Appendix II of the Convention on International Trade in
Endangered Species of Wild Fauna and Flora (CITES),[40] which by definition
means harvest from public land is prohibited and may require a permit to export,
although trade of the plants is not deemed to be detrimental to the wildlife
population and is otherwise unregulated. The U.S. Fish and Wildlife
Service recommends that diggers and harvesters track sales and harvests and
prove legality of all harvests.[41]
Canada, as well as 17 of the 27 U.S. states where goldenseal grows natively,
have declared it as threatened, vulnerable or uncommon.[41][42]More than 60
million goldenseal plants are picked each year without being
replaced.[43] Although goldenseal's geographical range is wide, it is found in
small quantities in these habitats.[3] The core of the herb's range is in the Ohio
River Valley,[3] but its population there has decreased by almost half.[44] The
process of mountain top removal mining has recently put the wild goldenseal
population at major risk from loss of habitat.[45]
Many herbalists urge caution in choosing products containing goldenseal, as
they may have been harvested in an unsustainable manner rather than having
been organically cultivated.
There are several berberine-containing plants that can serve as useful
alternatives, including Chinese coptis, yellowroot or Oregon grape root.[46]
Research on harvest effects
Research completed by Albrecht and McCarthy[47] shows that when
goldenseal is harvested in the fall season, it has a faster population recovery
than with midsummer harvests. However, a study by Douglas et al.[25] showed
that goldenseal has the highest concentrations of hydrastine and berberine in
the early summer. Their research also showed that three to five years of growth
will yield the highest concentration of alkaloids in the plant.[25]
Two experiments done by Sinclair and Catling[48][49] on the effects of soil
turnover, fertilization and transplanting of goldenseal show that disturbances
actually benefit the growth of goldenseal. The results from the first growing
season of the experiment showed that soil turnover and fertilization combined
show the greatest increase in plant biomass,[48]while the results after two
growing seasons showed that this group also yielded the highest proportion of
flowering plants, fruit production and seed production.[49] Both experiments
also showed that soil disturbances benefit the growth of goldenseal.[48][49]
Cultivation
As of 1998, only 2.4% of goldenseal plant material originated from a cultivated
source rather than wild harvest, although that number was projected to rise by
15–30% over the next several years.[41] In response to conservation concerns,
research has expanded regarding the propagation success of wild plant
material for commercial yield. Because goldenseal grows in patches of
interconnected ramets reproducing asexually through clonal propagation,
transplanting rhizome propagules into cultivated settings is
possible.[50][51][47] Seed propagation is also feasible and has advantages
such as lower cost and greater genetic variability, but is considered difficult and
unpredictable.[52][53]
Goldenseal may be commercially cultivated through agroforestry in natural
settings mirroring the plant's ecological environment, or on farms with artificial
shade canopies.[53][52] Another propagation method of goldenseal utilizes a
controlled environment such as a greenhouse growing lab where the plant's
environmental needs such as light, water and temperature are artificially
simulated. Crop selection and biotechnology experimentation may be employed
to increase yield and pharmacological potency.[54] Controlled environments
can greatly reduce the amount of time required to grow goldenseal to its desired
harvestable state. While forest-cultivated plants double in mass every three to
fiveyears, plants can double in mass every 15 weeks in growth chambers and
triple in growth when in a course soil medium.[55]Subculturing can take place
every 30 days to mass-propagate the plant.[56]
Another option is cultivating goldenseal in new regions. An experiment
conducted by Douglas et al.[57] grew goldenseal over a six-year period in a
warm, temperate environment in New Zealand. The yields were 74% higher in
the sixth year of growth compared to the fourth year of growth, which is when
goldenseal is normally harvested.[57] The overall growth of the allochthonous
goldenseal was comparable to that found in the United States, and the
hydrastine and berberine concentrations were within the American and
European standards.[57] Cultivating goldenseal in a New Zealand environment
that is similar to its home range is an option to maintain its population.[57]
See also

 Berberine
 Coptisine
 List of ineffective cancer treatments

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Literature

 Blanchan, Neltje (2005). Wild Flowers Worth Knowing. Project Gutenberg

Literary Archive Foundation. ISBN 0-665-98934-2.
 John Uri Lloyd (1908). Hydrastis canadensis. Lloyd Library, Cincinnati. PDF
 Bergner, Paul.(1997) The Healing Powers of Echinacea, Goldenseal and
Other Immune System Herbs. Prima ISBN 978-0-7615-0809-0
 W. Scott Persons and Jeanine M. Davis (2005) Growing & Marketing
Ginseng, Goldenseal & Other Woodland Medicinals Bright Mountain
Books. ISBN 978-0-914875-42-0
 Richo Cech. (2002) Growing At-Risk Medicinal Herbs, Cultivation,
Conservation and Ecology ISBN 978-0-9700312-1-1
 University of North Carolina, Dept. of Integrative Medicine. Monograph on
Goldenseal" https://web.archive.org/web/20080309154541/http://www.med.
unc.edu/phyrehab/ncmedicinalherbs/goldenseal/Goldenseal-hp.pdf

External links
Wikimedia Commons has media related to Goldenseal.

 Goldenseal: una bibliografía anotada

 Guía de hierbas y suplementos de About.com: Goldenseal
 Bruce A. Ford: Hydrastis en la flora de América del Norte, volumen 3