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

[Amazoniac]

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.

Spoiler: It's scary.

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

 

[Amazoniac]

Related:
- http://pubs.acs.org/doi/abs/10.1021/jf0486038
- Anti-infectious activity in plants of the genus Tabebuia

- http://www.tandfonline.com/doi/abs/10.1300/J044v02n04_05
- http://pubs.acs.org/doi/pdf/10.1021/np50059a044

Not sure if I'm going to read those but perhaps some of you are interested.
@Tabebuia georginosa - I forgot to tag you above.

 

[Travis]

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.

 

[haidut]

Lapachol and β-lapachone are the very best glyoxylase I inhibitors

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.

 

[Travis]

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.

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.

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.

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)​

 

[Amazoniac]

@Obi-wan @Travis @Amazoniac @haidut

Lapachol - Wikipedia

Once studied as a possible treatment for some types of cancer, it is now considered too toxic for use[1][2][3][4]​

1. Felício AC, Chang CV, Brandão MA, Peters VM, Guerra Mde O (2002). "Fetal growth in rats treated with lapachol". Contraception. 66 (4): 289–93. doi:10.1016/S0010-7824(02)00356-6. PMID 12413627.
2. Oral toxicology studies with lapachol. Morrison, Robert K.; Brown, Donald Emerson; Oleson, Jerome J.; Cooney, David A. Toxicology and Applied Pharmacology (1970), 17(1), 1-11.
3. Guerra Mde O, Mazoni AS, Brandão MA, Peters VM (2001). "Toxicology of Lapachol in rats: embryolethality". Brazilian journal of biology = Revista brasleira de biologia. 61 (1): 171–4. doi:10.1590/s0034-71082001000100021. PMID 11340475.
4. 
   de Cássia da Silveira E, Sá R, de Oliveira Guerra M (2007). "Reproductive toxicity of lapachol in adult male Wistar rats submitted to short-term treatment". Phytotherapy Research. 21 (7): 658–62. doi:10.1002/ptr.2141. PMID 17421057.

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.

 

[allblues]

@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?

 

[Travis]

@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?

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.

 

[TreasureVibe]

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.

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