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Is Pau D'Arco Really The Best Option Out Of The Tabebuia Buffet?

Discussion in 'Cancer, Degenerative Diseases' started by Amazoniac, Jan 13, 2018.

  1. Amazoniac

    Amazoniac Member

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    I was reading something about it and things didn't seem to connect. Wikipedia claims Tabebuia avellanedae and impetiginosa are the same thing for example, but apparently they're not. I have found studies comparing the development of a seed from one plant and the other, so of course they can't be the same.

    And then I came across this.
    Tabebuia acrophylla
    Tabebuia actinophylla
    Tabebuia acunana
    Tabebuia aesculifolia
    Tabebuia affinis
    Tabebuia alba
    Tabebuia anafensis
    Tabebuia angustata
    Tabebuia anisophylla
    Tabebuia apiculata
    Tabebuia aquatilis
    Tabebuia araliacea
    Tabebuia arenicola
    Tabebuia argentea
    Tabebuia arianeae
    Tabebuia arimaoensis
    Tabebuia atrovirens
    Tabebuia aurea
    Tabebuia avellanedae
    Tabebuia bahamensis
    Tabebuia barbata
    Tabebuia berterii
    Tabebuia berteroi
    Tabebuia beyeri
    Tabebuia bibracteolata
    Tabebuia billbergii
    Tabebuia botelhensis
    Tabebuia brevipes
    Tabebuia brigandina
    Tabebuia brooksiana
    Tabebuia buchii
    Tabebuia bullata
    Tabebuia bureauvii
    Tabebuia bureavii
    Tabebuia calcicola
    Tabebuia calderoni
    Tabebuia calderonii
    Tabebuia caleticana
    Tabebuia camagueyensis
    Tabebuia candicans
    Tabebuia capitata
    Tabebuia capotei
    Tabebuia caraiba
    Tabebuia cassinoides
    Tabebuia catarinensis
    Tabebuia chapadensis
    Tabebuia chrysantha
    Tabebuia chrysea
    Tabebuia chrysotricha
    Tabebuia citrifolia
    Tabebuia clementis
    Tabebuia coartata
    Tabebuia conferta
    Tabebuia coralibe
    Tabebuia cordata
    Tabebuia cowellii
    Tabebuia crassifolia
    Tabebuia crispiflora
    Tabebuia cristata
    Tabebuia cuneifolia
    Tabebuia curtissii
    Tabebuia del [what?]
    Tabebuia densifolia
    Tabebuia dentata
    Tabebuia dictyophylla
    Tabebuia diluvialis
    Tabebuia dolichopoda
    Tabebuia domingensis
    Tabebuia dominicensis
    Tabebuia donell-smithii
    Tabebuia donnell
    Tabebuia dracocephaloides
    Tabebuia dubia
    Tabebuia dugandii
    Tabebuia dura
    Tabebuia ecuadorensis
    Tabebuia ekmanii
    Tabebuia elegans
    Tabebuia elliptica
    Tabebuia elongata
    Tabebuia erosa
    Tabebuia excisa
    Tabebuia eximia
    Tabebuia fallax
    Tabebuia flavescens
    Tabebuia floccosa
    Tabebuia fluviatilis
    Tabebuia furfuracea
    Tabebuia fuscata
    Tabebuia gemmiflora
    Tabebuia geronensis
    Tabebuia glaucescens
    Tabebuia globiflora
    Tabebuia glomerata
    Tabebuia gonavensis
    Tabebuia gracilipes
    Tabebuia grisebachii
    Tabebuia guayacan
    Tabebuia haemantha
    Tabebuia heptaphylla
    Tabebuia heterophylla
    Tabebuia heteropoda
    Tabebuia heterotricha
    Tabebuia hotteana
    Tabebuia hypodictyon
    Tabebuia hypolepra
    Tabebuia hypoleuca
    Tabebuia ilicifolia
    Tabebuia imisspboy
    Tabebuia impetiginosa
    Tabebuia inaequipes
    Tabebuia incana
    Tabebuia insignis
    Tabebuia insignis
    Tabebuia ipe
    Tabebuia jackiana
    Tabebuia jamaicensis
    Tabebuia japurensis
    Tabebuia jaucoensis
    Tabebuia jojoana
    Tabebuia lanceolata
    Tabebuia lapacho
    Tabebuia latifolia
    Tabebuia leonis
    Tabebuia lepidophylla
    Tabebuia lepidota
    Tabebuia lepidota
    Tabebuia leptoneura
    Tabebuia leptopoda
    Tabebuia leucoxyla
    Tabebuia libanensis
    Tabebuia lindahlii
    Tabebuia linearis
    Tabebuia litoralis
    Tabebuia longiflora
    Tabebuia longipes
    Tabebuia lopezii
    Tabebuia lucida
    Tabebuia maestrensis
    Tabebuia magnolioides
    Tabebuia mansoana
    Tabebuia maxonii
    Tabebuia mexicana
    Tabebuia micrantha
    Tabebuia microphylla
    Tabebuia millsii
    Tabebuia moaensis
    Tabebuia mogotensis
    Tabebuia multinervis
    Tabebuia myrtifolia
    Tabebuia neochrysantha
    Tabebuia nervosa
    Tabebuia neurophylla
    Tabebuia nicaraguensis
    Tabebuia nigripes
    Tabebuia nipensis
    Tabebuia nivea
    Tabebuia nodosa
    Tabebuia nodosa
    Tabebuia obovata
    Tabebuia obscura
    Tabebuia obtusifolia
    Tabebuia ochracea
    Tabebuia odontodiscus
    Tabebuia oligolepis
    Tabebuia ophiolithica
    Tabebuia ophiticola
    Tabebuia orinocensis
    Tabebuia ostenfeldii
    Tabebuia ovatifolia
    Tabebuia pachyphylla
    Tabebuia pallida
    Tabebuia palmeri
    Tabebuia palustris
    Tabebuia paniculata
    Tabebuia papyrophloios
    Tabebuia pedicellata
    Tabebuia pentaphylla
    Tabebuia perelegans
    Tabebuia perfae
    Tabebuia pergracilis
    Tabebuia petrophila
    Tabebuia picotensis
    Tabebuia pilosa
    Tabebuia pinetorum
    Tabebuia pisoniana
    Tabebuia piutinga
    Tabebuia platyantha
    Tabebuia polyantha
    Tabebuia polymorpha
    Tabebuia potamophila
    Tabebuia pulcherrima
    Tabebuia pulverulenta
    Tabebuia pumila
    Tabebuia punctatissima
    Tabebuia pyramidata
    Tabebuia reticulata
    Tabebuia revoluta
    Tabebuia ricardii
    Tabebuia richardiana
    Tabebuia rigida
    Tabebuia riodocensis
    Tabebuia riparia
    Tabebuia roraimae
    Tabebuia rosea
    Tabebuia roseo
    Tabebuia roseo-alba
    Tabebuia rubriflora
    Tabebuia rufescens
    Tabebuia sauvallei
    Tabebuia schumanniana
    Tabebuia serratifolia
    Tabebuia striata
    Tabebuia umbellata
    Tabebuia vellosoi

    There are visible variances in some of these plants, so perhaps the bark varies as well. It's difficult after viewing such list to not question what makes impetiginosa special to be considered the best option out of those.

    @healthnatura @LifeGivingStore
     
  2. OP
    Amazoniac

    Amazoniac Member

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  3. Travis

    Travis Member

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    I think perhaps the best measure of these tree barks would be their lapachol and β-lapachone concentrations. I do remember reading studies which had measured these, but concentrations can of course vary widely. I'm pretty sure that all bark within the genus has lapachol, but exactly how much lapachol one specific batch has is anyone's guess.

    Lapachol and β-lapachone are the very best glyoxylase I inhibitors, and there is a surprising amount of cancer studies on these two molecules. Although a few other inhibitors have similar IC₅₀ levels, the pharmacokinetics of lapachol are the best. Curcumin inhibits glyoxylase too, like lapachol, but it is essentially unabsorbable; the polyphenol baicalein will make it to the bloodstream, yet it binds a bit too strongly to blood proteins for adequate dispersal.

    Tree barks are wonderful and go great with coffee; cinnamon, pau d'arco, and willow bark are all helpful.
     
  4. haidut

    haidut Member

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    What about plain quinones like 1,4-benzoquinone, 1,4-naphthoquinone and the 1,2 (ortho) varieties of both? I seem to remember reading studies showing that the naked quinones are even more potent than the lapachones.
     
  5. Travis

    Travis Member

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    I don't know. All of the good glyoxlyase I inhibitors, besides Thornalley's, are cyclic and have multiple hydroxl groups. This used to be well studied back in the '70s after the antitumor effect of methylglyoxal became undeniable; I think even the Pullman's—quantum chemists and Szent‐Györgyi's friends—worked on this:

    'There is currently considerable interest in the cellular metabolism of methylglyoxal (MG), stimulated by the investigations of Szent-Györgyi and co-workers [1-4], who showed that α-dicarbonyls were growth inhibitory and that methylglyoxal, in particular, is a normal constituent of tissue [5].' ―Thomson

    'The mechanism of this rearrangement is of considerable interest, since it has been shown that MG inhibits tumor growth [9,10]; and if it is involved in the control of cell division, as suggested by Szent-Györgyi [4], the inhibition of the glyoxalase enzyme may be a potential means of regulating growth. There is much experimental support for the inhibition of cellular growth by a variety of inhibitors of glyoxalase I.' ―Thomson

    'In selecting inhibitors of glyoxalase I, it would appear that one promising possibility would be that inhibitors mimic in some way the structure of one (or more) of the key intermediates. This is usually referred to as inhibition by transition state analogs, and investigations of this hypothesis have been reported by Douglas and Nadvi who showed that several compounds containing the enediol structure (Fig. 2) act as inhibitors, since one possible intermediate has this structure. However, there are other possible intermediates in this scheme. Lavery and Pullman [25] investigated by ab initio quantum mechanical calculations the energetics of the reactions through a variety of postulated intermediates, depicted in Figure 3, including the enediol.' ―Thomson

    'The present work is a further attempt to clarify the reaction scheme, and to suggest additional criteria for evaluation of the inhibitors of glyoxalase I, using both experimental studies of enzyme inhibition and quantum chemical studies of the various inhibitors and intermediates.' ―Thomson

    'Our work uses the structural data of Lavery and Pullman as a starting point for calculations on the possible intermediates. We have calculated the wavefunctions and electrostatic potential maps for the model enediol intermediate using the standard basis set, both with and without the Mg²⁺ ion, whose position was optimized, starting from the geometry used in Ref. [25]' ―Thomson

    'Apart from the CH₃– groups, all these molecules are planar, and nonplanar analogs are not inhibitory [26].' ―Thomson

    'The observation that the inhibitors must be planar supports the view that a common feature in these inhibitors is the existence of a variety with enediol-like features.' ―Thomson

    So diquinones could potentially be inhibitors, if their carbonyl groups are in the ortho position—such as in 1,2-benzoquinone.

    The molecules he found to be the best inhibitors are in the table below, along with an electron density map of the polyphenol escolutein. Also found in the article is a table of 'predicted inhibitors,' notable in the sense that it includes 2,3‐dihydroxybenzoquinone.

    electron density map.pngpotential inhibitors.pnginhibitors.png click to embiggen

    But listed here aren't even the best glyoxylase I inhibitors. The best one in the table above has an IC₅₀ of .03‧mM, or 30‧μM. Lapachol has an IC₅₀ around 9‧μM, and β-lapachone around 6‧μM—the most powerful one besides Thornalley's. Among the polyphenols, the one they had used—escolutein—is actually weaker than both myricetin and baicalein. Also deserving mention is curcumin, but this molecule is too large and lipophillic to be absorbed properly.

    Some polyphenols seem to work but they have different kinetics than the smaller molecules, binding to blood proteins and being excreted quickly in the urine. I think the small molecules such as β-lapachone, lapachol, and hinokitiol are probably the best—although 2,3‐dihydroxybenzoquinone surely seems like it would work.. .

    In another article, I found another inhibitory quinone: 2-Hydroxy-1,4-naphthoquinone

    '2-Hydroxy-1,4-naphthoquinone derivatives are reversible, competitive inhibitors of glyoxalase I. Lapachol is the most potent inhibitor studied with Kᵢ values of 37.5 μM (yeast enzyme), 97.5 μM (rat liver enzyme) and 8.25 μM (human-red blood cell enzyme). Henzopyran-4-one (flavonoid) and benzopyran-2-one (coumarin) derivatives also inhibit glyoxalase I. The most effective compounds studied with the yeast enzyme were coumarin-8 (Kᵢ = 3.5 μM), myricetin (Kᵢ = 5 μM), quercetin, 3-hydroxyflavone and purpurogallin (all with Kᵢ=9μM).' ―Allen

    The inhibitory concentration (Kᵢ) is a bit different than the IC₅₀, but there is enough data to get a clear picture. There are many more studies on glyoxylase I inhibitors than these two.

    active site.pngtable.png click to embiggen

    Of all the molecules mentioned above, β-lapachone probably has the most experimental data on cancer inhibition (found in pau d'arco).

    Thomson, Colin "Theoretical investigations of the structure of potential inhibitors of the enzyme glyoxalase‐I." International Journal of Quantum Chemistry (1983)
    Allen, Rosamund E. "Inhibitors of glyoxalase I: design, synthesis, inhibitory characteristics and biological evaluation." (1993)
    Li, Chiang J. "Induction of apoptosis by β-lapachone in human prostate cancer cells." Cancer research (1995)
     
  6. OP
    Amazoniac

    Amazoniac Member

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    The wormwood post got me thinking how brewing a tea using these barks compares with ingesting them whole, similar to cascara or cinnamon. burtlan commented how these plants contain a complex mix of compounds that makes them more effective in spite of lower doses of the main compound being needed, so less risk of toxicity (and resistance as well). On the other hand, there can be undesirable ones coming along in small amounts that can be the limiting factors for toxicity in their whole form.
     
  7. allblues

    allblues Member

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    @Travis Internet says lapachol has been found to be "too toxic for use [in cancer treatment/research]," any comments on this? Is it a dosage thing?
     
  8. Travis

    Travis Member

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    It's a vitamin K thing, in which it displaces from enzymes due to similarity. I think there is good reason to think that all side‐effects noted from taking lapachol are consequent of this one fact alone. This would mean than taking vitamin K with lapachol would eliminate all apparent toxicity.
     
  9. TreasureVibe

    TreasureVibe Member

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    Does taking Pau D'arco without vitamin K cause toxicity to the body?
     
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