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Transmissible Viral Vaccines... how the shots are affecting those who haven't taken it. They may be designed to do exactly that

J.R.K

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Aug 4, 2020
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1,168
Hey guys, remember how I posted that Walter Chestnut was saying Covid essentially turned your body into a one big horrific allergic overreaction?

Long Covid patients immediately turned up and said all of them are taking two types of antihistamines to control their symptoms.

Then people with Mast Cell Activation Syndrome showed up and said ivermectin helps them. They are apparently the people who were studied to determine that long-term weekly ivermectin was safe.

Now it looks like antihistamines MAY block spike proteins from binding to cells. One of the drugs that looks promising is Benadryl, though the dosing looks problematic:


The most effective antihistamine they tested was azelastine nasal spray. It appeared effective at lower than the usual prescribed dose. Others that might be effective appeared to require problematic doses.

I believe there have only been in vitro studies so far, but it's known that people over age 61 who use certain antihistamines have lower positive Covid-19 test rates.
Perhaps the use of cyproheptadine might also be beneficial then as well. Good news for people with the long haul issue though. I have a friend that has a friend that got COVID three months ago and still isn’t back to normal, no energy, motivation and sleep issues. Besides vitamin D and zinc Benadryl and Ivermectin may also help with this.
 

lvysaur

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Mar 15, 2014
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I know of a family friend whose mother was not vaccinated. Her relatives from abroad visited her (both vaccinated). She got sick and died after a couple of weeks.

Vaccines at the very least have no effect on transmissibility, if not a positive effect like OP claims
 

Vileplume

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Jun 10, 2020
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California
Hey guys, remember how I posted that Walter Chestnut was saying Covid essentially turned your body into a one big horrific allergic overreaction?

Long Covid patients immediately turned up and said all of them are taking two types of antihistamines to control their symptoms.

Then people with Mast Cell Activation Syndrome showed up and said ivermectin helps them. They are apparently the people who were studied to determine that long-term weekly ivermectin was safe.

Now it looks like antihistamines MAY block spike proteins from binding to cells. One of the drugs that looks promising is Benadryl, though the dosing looks problematic:


The most effective antihistamine they tested was azelastine nasal spray. It appeared effective at lower than the usual prescribed dose. Others that might be effective appeared to require problematic doses.

I believe there have only been in vitro studies so far, but it's known that people over age 61 who use certain antihistamines have lower positive Covid-19 test rates.
Peat has also recommended antihistamines as effective prevention against the spike protein.
 

Gone Peating

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Sep 16, 2018
Messages
1,006
There is a verifiable manager of an oil and gas recruiting business saying what actuaries are telling oil and gas execs and whom they are hiring her to replace.
But that makes no sense BC you won't be able to replace those people. The US wouldn't have the number of people necessary to do so. At that point the US would completely collapse.

I'm not denying that we will see those kinds of death numbers, just that I don't believe actuaries as a whole are telling oil and gas execs this info. Maybe one random one did
 

863127

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Messages
200
@Gone Peating

The binding affinity (strength) to the ACE2 receptor is different for different chemicals.

This study shows that SARS-CoV-2 variants bind to the ACE2 receptor with different strengths.


"...Here we present a rapid experimental method leveraging the speed and flexibility of Mircoscale Thermopheresis (MST) to characterize the interaction between Spike Receptor Binding Domain (RBD) and human ACE2 protein. The B.1.351 variant harboring three mutations, (E484K, N501Y, and K417N) binds the ACE2 at nearly five-fold greater affinity than the original SARS-COV-2 RBD. We also find that the B.1.1.7 variant, binds two-fold more tightly to ACE2 than the SARS-COV-2 RBD."

So we want to be aware of the strength of the binding affinity of what we use to prevent the virus from binding to ACE2, so that it can be stronger.

(But I don't know how to compare the data in that study (of the variant binding affinities) with what's in these studies below.)

I searched on Disroot SearX for:
ace2 receptor binding "affinity" black cumin

I found binding affinities for various chemicals in black cumin seed, and for other chemicals, including chloroquine and hydroxychloroquine to compare with.

__________


#1

"...Based on previously reported potential therapeutic uses of N. sativa compounds, and keeping in mind the dire need of time for the development of potent antiviral, a combined docking, ADMET properties calculation, molecular dynamics, and MM-PBSA approaches were applied in the current study to check the therapeutic potentials of N. sativa chief constituents against COVID-19. Among the studied compounds, we found that dithymoquinone (DTQ), with binding affinity of −8.6 kcal/mol compared to a positive control (chloroquine, −7.2 kcal/mol) , has the high potential of binding at SARS-CoV-2:ACE2 interface and thus could be predicted as a plausible inhibitor to disrupt viral-host interactions. Molecular dynamics simulation of 100 ns well complemented binding affinity of the compound and revealed strong stability of DTQ [dithymoquinone] at the docked site. Additionally, MM-PBSA also affirms the docking results. Compound DTQ of the present study, if validated in wet lab experiments, could be used to treat COVID-19 and could serve as a lead in the future for development of more effective natural antivirals against COVID-19.

...Among the studies compounds, DTQ [dithymoquinone] also known as nigellone, came out to be a more promising compound against the selected target. Nigellone, a carbonyl polymer of thymoquinone, retains its much of the pharmacologic properties (Chakravarty, 1993). Based on results of docking, dynamics, and net free energy value, we hypothesized that N. sativa compounds particularly DTQ [dithymoquinone] (Eid et al., 2017; Shrivastava et al., 2011) is showing high affinity and stability at SARS-CoV-2:ACE2 interface which upon binding with key residues of the interface may disrupt host recognition and also cure the viral infection by disrupting the S-protein pathway.

...DTQ showed a high affinity towards SARS-CoV-2:ACE2 interface and interacts with several hotspot residues both through hydrophobic and hydrophilic bonding. Additionally, this compound has high solubility, gut absorption, and good profile of druglikness making it a potent lead for future structure optimization to design more potent derivatives. Dynamically in an aqueous environment, the compound predicted conformation of docking studies is highly stable at CoV-2:ACE2 interface as affirmed by the binding free energy assays by securing a very low energy level."

[a table in the study showing the binding affinities of various chemicals in black cumin seed compared to chloroquine]

Binding affinites black cumin and chloroquine.png

__________

#2
Binding affinities of quercetin, hispidulin, cirsimaritin, sulfasalazine, artemisin, curcuma, hydroxychloroquine, thymoquinone, eugenol, N-acetylcysteine, and camphor



Binding affinites 2 1.png

Binding affinites 2 2.png

Binding affinities 2 3.png

__________

#3
Binding affinities of chemicals from cinnamon, black cumin seed, and andrographis (Andrographis paniculata)


"...Based on the lowest binding energy, confirmation, and H-bond interaction, cinnamic acid (−5.20 kcal/mol), thymoquinone (−4.71 kcal/mol), and andrographolide (Kalmegh) (−4.00 kcal/mol) were screened out showing strong binding affinity to the active site of ACE2 receptor. MD simulations suggest that cinnamic acid, thymoquinone, and andrographolide (Kalmegh) could efficiently activate the biological pathway without changing the conformation in the binding site of the ACE2 receptor..."

__________

So thymoquinone's binding affinity for ACE2 was different in each of the studies. I don't know enough about the chemistry to explain why. But with HCQ's binding affinity in the second study being -6.4 (kcal/mol), if I estimate it (because I don't know what I'm talking about and why it might not be exactly that) as between -6 and -7, and compare that to the binding affinities of the chemicals in black cumin seed shown in the first study, then...

yeah there things in black cumin seed that are as good as HCQ for binding to the ACE2 receptors. Thymoquinone apparently isn't the best chemical in black cumin seed to do that.
 
Last edited:

863127

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I was trying to figure out how to dose the black seed oil to get an amount of dithymoquinone close to the dosage of the HCQ protocol. Went down a bit of a rabbit hole about dithymoquinone... This also has information about the percent by weight of thymoquinone in the seeds and oil.

Okay, here we go. (Skip to the end for the very exacting recommendation of how to increase dithymoquinone content.)


"...the most important pharmacologically active phytochemicals of the black cumin are thymoquinone, thymohydroquinone , dithymoquinone, thymol and nigellone which are all present in both fixed and volatile oils (Ali and Blunden, 2003; Ahmed et al, 2013; Khan and Afzal, 2016)."

__________



"Interestingly, all the samples examined were found to contain only thymoquinone in significant amounts, and not the other derivatives such as dithymoquinone and thymohydroquinone. Although the percentages of thymoquinone vary for each sample, oils were found to contain higher amounts of thymoquinone compared to the seeds in general..."

Table 2. Concentrations and amounts of thymoquinone in seeds (in mg)

0.0098 - 0.376 %


Table 3. Concentrations and amounts of thymoquinone in seed oils (in mg)

0.050 - 0.619 %


__________



...Houghton et al. [7] have measured the content of TQ in N. sativa seed oil samples from different origins by gas chromatography analysis, and found it to be in the range of 0.13–0.17% w/v of the oil.

__________


Very detailed review of the composition of black seed oil

A Comprehensive Review of the Physicochemical, Quality and Nutritional Properties of Nigella Sativa Oil
by Mazaheri et al., 2019

Sci-Hub | A Comprehensive Review of the Physicochemical, Quality and Nutritional Properties of Nigella Sativa Oil. Food Reviews International, 1–21 | 10.1080/87559129.2018.1563793

But I only see a mention of dithymoquinone.

__________


Found this about black cumin CO2 extract.


Chemical composition of Nigella sativa L. seed extracts obtained by supercritical carbon dioxide by Venkatachallam et al., 2010

"Chemical composition of black cumin (Nigella sativa L.) seed extracts obtained by supercritical carbon dioxide... Forty-seven volatile compounds were detected where sixteen compounds were reported for the first time in the oil of this seed. Moreover,thymoquinone (TQ), dithymoquinone (DTQ), thymohydroquinone (THQ) and thymol (THY) were the major phenolic compounds. It can be concluded that the chemical composition of extracts obtained by SC CO2 extraction of the seeds showed better recovery of phenolic compounds than HD SFE [hydrodistillation of the CO2 extract to make an essential oil from the CO2 extract] and proved the occurrence of thermally labile or photosensitive bioactive volatiles of four major quinonic phenol compounds... The lower number of compounds occurred in HD SFE compared to SFE is mainly related to the possible degradation of volatile compounds by higher temperature and longer distillation time...

In this study, dithymoquinone (DTQ) could not be traced by GC and GC-MS analysis of these oils, as confirmed by Burits and Bucar (2000) and Benkaci-Ali et al. (2007)."


So no dithymoquinone in the CO2 extract.

__________


Fatty acid profile, thymoquinone content, oxidative stability, and antioxidant properties of cold pressed black cumin seed oils
by Lutterodt et al., 2010


"Black cumin seed oil contained about 3.48–8.73 mg/g thymoquinone and trace amount of dithymoquinone..."

Table 2 -- Thymoquinone content in six samples of oil

3.48 - 8.73 mg per gram of oil


"In the present study, the six cold-pressed black cumin seed oils were assessed for their levels of thymoquinone and its related compounds, including dithymoquinone and thymol. Thymol was not detected in any of the oil samples, and only trace amount of dithymoquinone was detected in the black cumin seed oil... Furthermore, it was suggested that the level of dithymoquinone in a sample of black cumin seed oil may indicate the nature of the manufacturing procedures used to produce the oil, as well as its conditions of storage such as exposure to light and heat (Gosheh et al., 1999). The low level of dithymoquinone in the black cumin seed oils may be explained by the fact that they were cold-pressed and stored under nitrogen in the dark until analysis."


Gosheh, O. A., Houdi, A. A., & Crooks, P. A. (1999). High performance liquid chromatographic analysis of the pharmacologically active quinines and related
compounds in the oil of the black seed (Nigella sativa L). Journal of Pharmaceutical & Biomedical Analysis, 19, 757e762.


Mahfouz and El-Dakhakhny [9] reported the isolation of the antihistaminic ‘nigellone’ [4], a substance extracted from the oil of N. sativa seed, using Girard’s reagent. El Dakhakhny [10] also isolated thymoquinone (TQ) from the essential oil of the seed, and determined that the ‘nigellone’ isolated earlier was a dimer of thymoquinone, which they named dithymoquinone (DTQ). DTQ is formed during various stages of extraction and separation of the quinones from the seed.

Assays of samples taken from the seed oil are shown in Table 2 and Fig. 3.

Dithymoquinone not quantifiable.png

It was found that the amount of TQ present in this source of commercial oil was about one third that found in other commercial sources of oils [7]. In this commercial oil, DTQ was not detectable, however, the presence of DTQ is still an important constituent in seed oil, especially with regard to the nature of the extraction and manufacturing procedures utilized to generate the seed oil. In earlier studies, the major quinone constituent of the seed was thought to be DTQ (termed ‘nigellone’ by earlier workers), and was shown to be formed via photodimerization of TQ [thymoquinone] as a consequence of exposure to sunlight during separation and extraction procedures [10]. Various storage conditions are expected to make a difference in the amounts of the quinone constituents of the oil, especially if seed oil samples are exposed to heat and light."


[10] M. El-Dakhakhny, Planta Med. 11 (1963) 465–470. STUDIES ON THE CHEMICAL CONSTITUTION OF EGYPTIAN NIGELLA SATIVA L. SEEDS. II1) THE ESSENTIAL OIL.

I didn't find the full version of that. From the abstract:

"Thymoquinone also dimerized into dithymoquinone."

( Thieme E-Journals - Planta Medica / Abstract )

___________


Okay so exposure to heat and/or light are needed to make thymoquinone into dithymoquinone?

Exposure to light is. Dithymoquinone is a photodimer of thymoquinone, meaning light makes thymoquinone become dithymoquinone.

So more detail about how to do that...

A Practical Synthesis and X-ray Crystallographic Analysis of Dithymoquinone, a Photodimer of Thymoquinone by Myers et al., 2014


"An updated and practical approach to the synthesis of dithymoquinone via one-step photoirradiation of thymoquinone... is described. Synthesis resulted in a 55% yield of one structural isomer...

Thymoquinone... is a bright yellow crystalline compound that... was originally isolated from the essential oil of black cumin seeds using silica gel chromatography by El-Dakhakhany in 1963 [9]. Highly pure (>99%) and relatively cost-efficient preparations of [thymoquinone] can be purchased through commercial sources (e.g. Sigma-Aldrich Co.), but [thymohydroquinone] and [dithymoquinone] are not as readily available...

The first significant reports on the synthesis of dithymoquinone ((4b,8b-dimethyl-3,7-di(propan-2-yl)- 4a,8a-dihydrobiphenylene-1,4,5,8-tetrone; 3), a photodimer derivative of [thymoquinone], were published in the late 1800’s [11, 12], and expanded upon by Smith and Tess in 1944 [13]. In the latter report a highly concentrated ethereal solution of [thymoquinone] was evaporated to a thin, polycrystalline film and exposed to indirect daylight for seven days. After photo conversion, [dithymoquinone] was purified by crystallization in ethanol to pale yellow needle-like crystals [13]. Since then only slight modifications to these procedures have been published. In addition, these reports contain only brief and very limited descriptions of the synthesis [6, 7, 9, 14–17]. As our laboratory is interested in measuring the concentrations of [thymoquinone], [thymohydroquinone] and [dithymoquinone] in commercial black seed oil preparations and their pharmacological activities in vitro and in vivo studies, we needed to be able to prepare multi-gram quantities of purified [dithymoquinone]. This was the impetus for our attempts to develop a concise and simple synthesis of [dithymoquinone]. Herein we describe a simple, practical synthesis of [dithymoquinone] which expands upon previous methods.

Our synthesis commenced with dissolving 1 in a minimal volume of ethyl acetate. Two 32-watt linear fluorescent tube bulbs housed in a fume hood (Thermo Hamilton Safe Aire II) served as the light source, which is a practical approach for irradiation of [thymoquinone]. Irradiation sources reported elsewhere include: diffused light [9], indirect sunlight [13, 14], daylight [7], 400 watt mercury vapor lamp [15] and a xenon lamp [16]."


Diffused light

9. El-Dakhakhany M. Studies on the chemical constitution of Egyptian nigella sativa l. Seeds. II: The essential oil. Planta Med. 1963;12:465–470.


Indirect sunlight

13. Smith LI, Tess RWH. Dithymoquinone. J. Am. Chem. Soc. 1944;66:1323–1325.

"[Dithymoquinone] was prepared by the action of light upon thin layers of thymoquinone; when crystallized from ethanol, it formed long, light yellow needles melting at 200-201 degrees and resembling anthraquinone in appearance. The substance was quite stable, and was sparingly soluble in all the usual solvents. Reduction, by a variety of methods, gave thymohydroquinone... When quickly heated, the dimer [dithymoquinone] could be distilled at 232 degrees (the boiling point of the monomer [thymoquinone], and the distillate contained thymoquinone ... The only method found for preparation of the quinone was the original one -- illumination of thing layers of the monomer [thymoquinone], when the dimer resulted in 76% yields."


So indirect sunlight could convert some thymoquinone to dithymoquinone, but don't boil the oil because boiling would change the dithymoquinone back to thymoquinone?


Upregulation of chemoprotective enzymes and glutathione by Nigella sativa (black seed) and thymoquinone in CCl4-intoxicated rats.
El-Sayed WM
Int J Toxicol. 2011 Dec; 30(6):707-14.


"Dithymoquinone (DTQ) was prepared from the dimerization of TQ. A flask containing an ether solution of TQ (0.99 g, 0.01 mol) in a minimum volume of ether was whirled continuously until the ether completely evaporated leaving a thin layer of TQ [thymoquinone]. This was left in indirect sunlight for 1 week. Recrystallization of the product from 80% ethanol gave very pale yellow needles of DTQ, with 83% yield. The crystals were collected by vacuum filtration and dried overnight under vacuum..."


Daylight

7. Petrucci R, Marrosu G, Astolfi P, Lupidi G, Greci L. Cyclic voltammetry, spectroelectrochemistry and electron spin resonance as combined tools to study thymoquinone in aprotic medium. Electrochim. Acta. 2012;60:230–238.


"...dithymoquinone (DTQ), the TQ dimer formed through a well described process upon light exposure [30], was also studied...

[30] E. Zavarin, J. Org. Chem. 23 (1958) 47"

On the Structure of the Photodimer of Thymoquinone by Eugene Zavarin, 1958


"The chemistry of the dimer of thymoquinone formed by irradiating the quinone in thin crystalline layers with daylight has been the subject of several papers. The material consists of pale yellow crystals that melt at 200-201° and on further heating, dissociate to give thymoquinone. On reduction by a variety of reagents, hydrothymoquinone is formed..."


Mercury vapor lamp

15. Robbins RJ, Falvey DE. Radical anion reactions of cyclobutane derivatives: Electron-transfer cleavage of dithymoquinone. J. Org. Chem. 1993;58:3616–3618.



Xenon lamp

16. Robbins RJ, Falvey DE. Stereochemistry of the solid state photodimerization of thymoquinone. Tetrahedron Lett. 1993;34:3509–3510.


"Dithymoquinone (2) was prepared by Xenon lamp irradiation of a thin, polycrystalliie film of [thymoquinone]."

__________


Okay, so back to before the details of the methods to make thymoquinone into dithymoquinone... This:

"In earlier studies, the major quinone constituent of the seed was thought to be DTQ [dithymoquinone] (termed ‘nigellone’ by earlier workers), and was shown to be formed via photodimerization of TQ [thymoquinone] as a consequence of exposure to sunlight during separation and extraction procedures [10]. Various storage conditions are expected to make a difference in the amounts of the quinone constituents of the oil, especially if seed oil samples are exposed to heat and light."
( Sci-Hub | High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.). Journal of Pharmaceutical and Biomedical Analysis, 19(5), 757–762 | 10.1016/S0731-7085(98)00300-8 )


So if dithymoquinone was common enough in early studies to be thought to be the main quinone in black seed oil, unless they were all making thin crystalline layers of it before putting it in the sun that isn't necessary; just put a clear glass bottle of black seed oil in the sun (it can be indirect sun) like if it were in an outdoor market or a kitchen, and some thymoquinone will photodimerize to dithymoquinone?
 
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Makrosky

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Oct 5, 2014
Messages
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I have a noticed feeling better and overall mental calmness when i take it especially since I started taking it in the mornings right before i walk out the door. I feel really calm as I start my route in the van and i don't remember feeling that way as often - i don't know if this is a benefit of it but I noticed it immediately after switching to the morning so there may be something to it.
The other big thing that I attribute to it is my hands used to shake quite a bit some days - so much that I'd spill some of my liquid multi-vitamin and the black seed oil when i'd try to take it in a tsp. (This started about 10-11 years ago). I don't take the multi as often after becoming a Peat guy but i've stuck with the black seed oil. Anyway I noticed a few months ago i wasn't haven't the shaking hands hardly at all and do not spill any liquid doses. I started taking black seed oil last October/November and by February I noticed this. I also improved my diet by eating more Peat foods so this could be it but intuitively I've always felt the black seed oil really helps me and was the reason for this improvement although can't prove it.
Amazing! Thanks! Yes it is totally normal you feel more calm by the way. Thymoquinone modulates GABA.
 

Makrosky

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Messages
3,668
So basically it can substitute for HCQ?
I haven't done any kind of research on that @Nemo is the expert, but I would say IVM and HCQ are much powerful.

Black cumin, cloves, NAC, etc. is 2nd option for a mild prophylaxis.

Edit: 863127 has posted about this just a few posts up.
 
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863127

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Jan 29, 2021
Messages
200
So even though we know the binding affinities for quinones in black seed oil compared to chloroquine and HCQ, I still don't know what dosage of black seed oil would be as effective as the Zelenko protocol's HCQ dosage,,,

"Zelenko Protocol for High Risk Patients:
...Hydroxychloroquine (HCQ) 200mg 1 time a day for 5 days, then 1 time a week..."
(Zelenko Prophylaxis Protocol - DR Vladimir Zelenko MD)

...because I don't think 200 mg of thymoquinone or dithymoquinone is the amount needed to protect the ACE2 receptors just because it's 200 mg of HCQ...?

If the conversion of thymoquinone to dithymoquinone from sun is 25% or 50% (the laboratory results were higher yield, but I'm talking about just putting a clear glass bottle in the sun (and maybe those percentages are too high for doing that?)), then the concentration of DTQ in the oil would be...

(from one of the studies in my previous post)

"Black cumin seed oil contained about 3.48–8.73 mg/g"

-- if 25% TQ to DTQ conversion: 0.87 - 2.1825 mg/g DTQ/oil
-- if 50% TQ to DTQ conversion: 1.74 - 4.365 mg/g DTQ/oil

To get 200 mg DTQ, that'd be
-- (if 25%) 91 - 229 grams of oil
-- (if 50%) 46 - 115 grams of oil

But then how to convert grams weight of the oil to volume, to know how many ounces of oil for those dosages? With a bottle of the oil and a scale I don't have.
 

Peatness

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I've been thinking about the use of antiglycation supplements such as thiamine for the spike protein.

Anti-Glycation Supplements

Pyridoxal-5’-phosphate
(Vitamin B6)
Riboflavin
Selenium Yeast:
Silymarin/Milk Thistle
Taurine
Thiamine
Vitamin C&E
(plus bioflavonoids)
Whole Spices and Herbs
Zinc

Aged Garlic Extract
Carnitine
Carnosine
Catechins
Coenzyme Q10
Curcumin and Turmeric

 

Attachments

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Nemo

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So basically it can substitute for HCQ?

Here's the difference, GP.

We have studies showing ivermectin and HCQ block spike proteins and block other effects of the spike protein. We have studies of their effective use in patients.

We have no studies on black cumin seeds. We might be able to make an educated guess on how well it would work if we looked at the structure of thymoquinone. And the fact that it's used in ayurvedic medicine is a strong plus.

@863127 does a good job of trying to calculate an equivalent dose. But we know that some of the quinolines, including HCQ, work great against spike protein prions while others that looked good in a petri dish didn't get into the brain at all in animal trials.

Some drugs, like fenbendazole, looked like they would be great against the spike protein, but they turned out not to affect ACE2 binding, only binding to another receptor. That wasn't enough to make fenbendazole an effective treatment by itself.

In professional gambling, the MIT blackjack team came up with a method of bet sizing that not only took into account your edge, but a "certainty equivalent". Let's say you have a bet with a ridiculously high edge, like 50%. (On average, you expect to make a 50% return on your bet over the long run.) But it would be perfectly normal to lose the bet 10 times in a row.

In Kelly betting, the traditional method of bet sizing, you would bet 50% of your bankroll on that bet. A conservative player might bet 25%, or 12.5%. But too often you would effectively wipe out your ability to function as a professional gambler if you sized your bets that way.

When you take black cumin seeds instead of ivermectin or HCQ, you have to ask yourself how certain you are that it will work, because you're betting your life. If you're in a high-risk situation with low certainty, you're mathematically screwed.
 

Nemo

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Messages
2,163
Curious on your thoughts about navel application? I have had what I feel is good results for progesterone and other vitamins. I think Haidut has a study that indicates navel applications are equivalent to injection into the bloodstream, hence where I got the idea and in my opinion there is some merit for the idea. I wonder if it would be effective for this?

I think that's a great idea.
 

akgrrrl

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Location
Alaska
See, this is something you can use on family that can't hear you.

Grind up some black cumin seeds into chili or a curry, have them over for dinner.

I was trying to figure out how to dose the black seed oil to get an amount of dithymoquinone close to the dosage of the HCQ protocol. Went down a bit of a rabbit hole about dithymoquinone... This also has information about the percent by weight of thymoquinone in the seeds and oil.

Okay, here we go. (Skip to the end for the very exacting recommendation of how to increase dithymoquinone content.)


"...the most important pharmacologically active phytochemicals of the black cumin are thymoquinone, thymohydroquinone , dithymoquinone, thymol and nigellone which are all present in both fixed and volatile oils (Ali and Blunden, 2003; Ahmed et al, 2013; Khan and Afzal, 2016)."

__________



"Interestingly, all the samples examined were found to contain only thymoquinone in significant amounts, and not the other derivatives such as dithymoquinone and thymohydroquinone. Although the percentages of thymoquinone vary for each sample, oils were found to contain higher amounts of thymoquinone compared to the seeds in general..."

Table 2. Concentrations and amounts of thymoquinone in seeds (in mg)

0.0098 - 0.376 %


Table 3. Concentrations and amounts of thymoquinone in seed oils (in mg)

0.050 - 0.619 %


__________



...Houghton et al. [7] have measured the content of TQ in N. sativa seed oil samples from different origins by gas chromatography analysis, and found it to be in the range of 0.13–0.17% w/v of the oil.

__________


Very detailed review of the composition of black seed oil

A Comprehensive Review of the Physicochemical, Quality and Nutritional Properties of Nigella Sativa Oil
by Mazaheri et al., 2019

Sci-Hub | A Comprehensive Review of the Physicochemical, Quality and Nutritional Properties of Nigella Sativa Oil. Food Reviews International, 1–21 | 10.1080/87559129.2018.1563793

But I only see a mention of dithymoquinone.

__________


Found this about black cumin CO2 extract.


Chemical composition of Nigella sativa L. seed extracts obtained by supercritical carbon dioxide by Venkatachallam et al., 2010

"Chemical composition of black cumin (Nigella sativa L.) seed extracts obtained by supercritical carbon dioxide... Forty-seven volatile compounds were detected where sixteen compounds were reported for the first time in the oil of this seed. Moreover,thymoquinone (TQ), dithymoquinone (DTQ), thymohydroquinone (THQ) and thymol (THY) were the major phenolic compounds. It can be concluded that the chemical composition of extracts obtained by SC CO2 extraction of the seeds showed better recovery of phenolic compounds than HD SFE [hydrodistillation of the CO2 extract to make an essential oil from the CO2 extract] and proved the occurrence of thermally labile or photosensitive bioactive volatiles of four major quinonic phenol compounds... The lower number of compounds occurred in HD SFE compared to SFE is mainly related to the possible degradation of volatile compounds by higher temperature and longer distillation time...

In this study, dithymoquinone (DTQ) could not be traced by GC and GC-MS analysis of these oils, as confirmed by Burits and Bucar (2000) and Benkaci-Ali et al. (2007)."


So no dithymoquinone in the CO2 extract.

__________


Fatty acid profile, thymoquinone content, oxidative stability, and antioxidant properties of cold pressed black cumin seed oils
by Lutterodt et al., 2010


"Black cumin seed oil contained about 3.48–8.73 mg/g thymoquinone and trace amount of dithymoquinone..."

Table 2 -- Thymoquinone content in six samples of oil

3.48 - 8.73 mg per gram of oil


"In the present study, the six cold-pressed black cumin seed oils were assessed for their levels of thymoquinone and its related compounds, including dithymoquinone and thymol. Thymol was not detected in any of the oil samples, and only trace amount of dithymoquinone was detected in the black cumin seed oil... Furthermore, it was suggested that the level of dithymoquinone in a sample of black cumin seed oil may indicate the nature of the manufacturing procedures used to produce the oil, as well as its conditions of storage such as exposure to light and heat (Gosheh et al., 1999). The low level of dithymoquinone in the black cumin seed oils may be explained by the fact that they were cold-pressed and stored under nitrogen in the dark until analysis."


Gosheh, O. A., Houdi, A. A., & Crooks, P. A. (1999). High performance liquid chromatographic analysis of the pharmacologically active quinines and related
compounds in the oil of the black seed (Nigella sativa L). Journal of Pharmaceutical & Biomedical Analysis, 19, 757e762.


Mahfouz and El-Dakhakhny [9] reported the isolation of the antihistaminic ‘nigellone’ [4], a substance extracted from the oil of N. sativa seed, using Girard’s reagent. El Dakhakhny [10] also isolated thymoquinone (TQ) from the essential oil of the seed, and determined that the ‘nigellone’ isolated earlier was a dimer of thymoquinone, which they named dithymoquinone (DTQ). DTQ is formed during various stages of extraction and separation of the quinones from the seed.

Assays of samples taken from the seed oil are shown in Table 2 and Fig. 3.

View attachment 24599

It was found that the amount of TQ present in this source of commercial oil was about one third that found in other commercial sources of oils [7]. In this commercial oil, DTQ was not detectable, however, the presence of DTQ is still an important constituent in seed oil, especially with regard to the nature of the extraction and manufacturing procedures utilized to generate the seed oil. In earlier studies, the major quinone constituent of the seed was thought to be DTQ (termed ‘nigellone’ by earlier workers), and was shown to be formed via photodimerization of TQ [thymoquinone] as a consequence of exposure to sunlight during separation and extraction procedures [10]. Various storage conditions are expected to make a difference in the amounts of the quinone constituents of the oil, especially if seed oil samples are exposed to heat and light."


[10] M. El-Dakhakhny, Planta Med. 11 (1963) 465–470. STUDIES ON THE CHEMICAL CONSTITUTION OF EGYPTIAN NIGELLA SATIVA L. SEEDS. II1) THE ESSENTIAL OIL.

I didn't find the full version of that. From the abstract:

"Thymoquinone also dimerized into dithymoquinone."

( Thieme E-Journals - Planta Medica / Abstract )

___________


Okay so exposure to heat and/or light are needed to make thymoquinone into dithymoquinone?

Exposure to light is. Dithymoquinone is a photodimer of thymoquinone, meaning light makes thymoquinone become dithymoquinone.

So more detail about how to do that...

A Practical Synthesis and X-ray Crystallographic Analysis of Dithymoquinone, a Photodimer of Thymoquinone by Myers et al., 2014


"An updated and practical approach to the synthesis of dithymoquinone via one-step photoirradiation of thymoquinone... is described. Synthesis resulted in a 55% yield of one structural isomer...

Thymoquinone... is a bright yellow crystalline compound that... was originally isolated from the essential oil of black cumin seeds using silica gel chromatography by El-Dakhakhany in 1963 [9]. Highly pure (>99%) and relatively cost-efficient preparations of [thymoquinone] can be purchased through commercial sources (e.g. Sigma-Aldrich Co.), but [thymohydroquinone] and [dithymoquinone] are not as readily available...

The first significant reports on the synthesis of dithymoquinone ((4b,8b-dimethyl-3,7-di(propan-2-yl)- 4a,8a-dihydrobiphenylene-1,4,5,8-tetrone; 3), a photodimer derivative of [thymoquinone], were published in the late 1800’s [11, 12], and expanded upon by Smith and Tess in 1944 [13]. In the latter report a highly concentrated ethereal solution of [thymoquinone] was evaporated to a thin, polycrystalline film and exposed to indirect daylight for seven days. After photo conversion, [dithymoquinone] was purified by crystallization in ethanol to pale yellow needle-like crystals [13]. Since then only slight modifications to these procedures have been published. In addition, these reports contain only brief and very limited descriptions of the synthesis [6, 7, 9, 14–17]. As our laboratory is interested in measuring the concentrations of [thymoquinone], [thymohydroquinone] and [dithymoquinone] in commercial black seed oil preparations and their pharmacological activities in vitro and in vivo studies, we needed to be able to prepare multi-gram quantities of purified [dithymoquinone]. This was the impetus for our attempts to develop a concise and simple synthesis of [dithymoquinone]. Herein we describe a simple, practical synthesis of [dithymoquinone] which expands upon previous methods.

Our synthesis commenced with dissolving 1 in a minimal volume of ethyl acetate. Two 32-watt linear fluorescent tube bulbs housed in a fume hood (Thermo Hamilton Safe Aire II) served as the light source, which is a practical approach for irradiation of [thymoquinone]. Irradiation sources reported elsewhere include: diffused light [9], indirect sunlight [13, 14], daylight [7], 400 watt mercury vapor lamp [15] and a xenon lamp [16]."


Diffused light

9. El-Dakhakhany M. Studies on the chemical constitution of Egyptian nigella sativa l. Seeds. II: The essential oil. Planta Med. 1963;12:465–470.


Indirect sunlight

13. Smith LI, Tess RWH. Dithymoquinone. J. Am. Chem. Soc. 1944;66:1323–1325.

"[Dithymoquinone] was prepared by the action of light upon thin layers of thymoquinone; when crystallized from ethanol, it formed long, light yellow needles melting at 200-201 degrees and resembling anthraquinone in appearance. The substance was quite stable, and was sparingly soluble in all the usual solvents. Reduction, by a variety of methods, gave thymohydroquinone... When quickly heated, the dimer [dithymoquinone] could be distilled at 232 degrees (the boiling point of the monomer [thymoquinone], and the distillate contained thymoquinone ... The only method found for preparation of the quinone was the original one -- illumination of thing layers of the monomer [thymoquinone], when the dimer resulted in 76% yields."


So indirect sunlight could convert some thymoquinone to dithymoquinone, but don't boil the oil because boiling would change the dithymoquinone back to thymoquinone?


Upregulation of chemoprotective enzymes and glutathione by Nigella sativa (black seed) and thymoquinone in CCl4-intoxicated rats.
El-Sayed WM
Int J Toxicol. 2011 Dec; 30(6):707-14.


"Dithymoquinone (DTQ) was prepared from the dimerization of TQ. A flask containing an ether solution of TQ (0.99 g, 0.01 mol) in a minimum volume of ether was whirled continuously until the ether completely evaporated leaving a thin layer of TQ [thymoquinone]. This was left in indirect sunlight for 1 week. Recrystallization of the product from 80% ethanol gave very pale yellow needles of DTQ, with 83% yield. The crystals were collected by vacuum filtration and dried overnight under vacuum..."


Daylight

7. Petrucci R, Marrosu G, Astolfi P, Lupidi G, Greci L. Cyclic voltammetry, spectroelectrochemistry and electron spin resonance as combined tools to study thymoquinone in aprotic medium. Electrochim. Acta. 2012;60:230–238.


"...dithymoquinone (DTQ), the TQ dimer formed through a well described process upon light exposure [30], was also studied...

[30] E. Zavarin, J. Org. Chem. 23 (1958) 47"

On the Structure of the Photodimer of Thymoquinone by Eugene Zavarin, 1958


"The chemistry of the dimer of thymoquinone formed by irradiating the quinone in thin crystalline layers with daylight has been the subject of several papers. The material consists of pale yellow crystals that melt at 200-201° and on further heating, dissociate to give thymoquinone. On reduction by a variety of reagents, hydrothymoquinone is formed..."


Mercury vapor lamp

15. Robbins RJ, Falvey DE. Radical anion reactions of cyclobutane derivatives: Electron-transfer cleavage of dithymoquinone. J. Org. Chem. 1993;58:3616–3618.



Xenon lamp

16. Robbins RJ, Falvey DE. Stereochemistry of the solid state photodimerization of thymoquinone. Tetrahedron Lett. 1993;34:3509–3510.


"Dithymoquinone (2) was prepared by Xenon lamp irradiation of a thin, polycrystalliie film of [thymoquinone]."

__________


Okay, so back to before the details of the methods to make thymoquinone into dithymoquinone... This:

"In earlier studies, the major quinone constituent of the seed was thought to be DTQ [dithymoquinone] (termed ‘nigellone’ by earlier workers), and was shown to be formed via photodimerization of TQ [thymoquinone] as a consequence of exposure to sunlight during separation and extraction procedures [10]. Various storage conditions are expected to make a difference in the amounts of the quinone constituents of the oil, especially if seed oil samples are exposed to heat and light."
( Sci-Hub | High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.). Journal of Pharmaceutical and Biomedical Analysis, 19(5), 757–762 | 10.1016/S0731-7085(98)00300-8 )


So if dithymoquinone was common enough in early studies to be thought to be the main quinone in black seed oil, unless they were all making thin crystalline layers of it before putting it in the sun that isn't necessary; just put a clear glass bottle of black seed oil in the sun (it can be indirect sun) like if it were in an outdoor market or a kitchen, and some thymoquinone will photodimerize to dithymoquinone?
I am so grateful that you posted this and here is why: i have tried and tried to explain that mass spec and chromography technology has proved over and over that all distilled "essential" oils are not the same, that most only smell and have zero therapeutics...that we "lost" the use and full realization of plant compounds for nearly 1,000 years, from a time when they were the currency of the old world. Because I point out that the resurgence is due to the work of D.Gary Young who I had the good fortune to work with a few times, whose company has disclosed compound profiles along with specifics on rates of heat, temp distillation, storage, harvesting, and growing environs as variants. After being labeled a "shill" here for that, I suppose revealing a day when I was part of a team harvesting/distilling Melissa, it was discovered the compound profile for material which was cut and laid on the ground for several hours was remarkably different than combine harvested/loaded kept off the ground--- would make me a quack too. Any bottler who outsources distillation and growing has no idea or care what the compounds are.if they wont let you tour their operations or provide technical information, they are piggybacking for dollars on his 30yrs work and 20 worldwide farms.
 

Nemo

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I am so grateful that you posted this and here is why: i have tried and tried to explain that mass spec and chromography technology has proved over and over that all distilled "essential" oils are not the same, that most only smell and have zero therapeutics...that we "lost" the use and full realization of plant compounds for nearly 1,000 years, from a time when they were the currency of the old world. Because I point out that the resurgence is due to the work of D.Gary Young who I had the good fortune to work with a few times, whose company has disclosed compound profiles along with specifics on rates of heat, temp distillation, storage, harvesting, and growing environs as variants. After being labeled a "shill" here for that, I suppose revealing a day when I was part of a team harvesting/distilling Melissa, it was discovered the compound profile for material which was cut and laid on the ground for several hours was remarkably different than combine harvested/loaded kept off the ground--- would make me a quack too. Any bottler who outsources distillation and growing has no idea or care what the compounds are.if they wont let you tour their operations or provide technical information, they are piggybacking for dollars on his 30yrs work and 20 worldwide farms.

I'd welcome hearing more about what you think about how to use black cumin seeds, akgrrrl.

They're being recommended by practioners of ayurvedic medicine. We know they have thymoquinone in them. Since they're recommending it for prions I assume the thymoquinone or dithymoquinone gets across the blood brain barrier.
 

akgrrrl

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I'd welcome hearing more about what you think about how to use black cumin seeds, akgrrrl.

They're being recommended by practioners of ayurvedic medicine. We know they have thymoquinone in them. Since they're recommending it for prions I assume the thymoquinone or dithymoquinone gets across the blood brain barrier.
I have wondered about black seed oil as well. So, it is a good question, and here some wandering thoughts. We know that distillation of plants into oils can magnify the constituents as many as 10K times. But oils are not simple. They often contain 80 to 300 or more constituents, dependent on growing methods, harvest timing, soil, water. We are told these variables are the reason that synthetic compounds are better; they are more reliable. There is much to know about botanicals, and most of us-- rare the time to drill down. How is one to know if the thymol is present in high enough quantities, in the leaf/seed/root that we seek? Lets say you have a bottle labeled Basil(ocimum basilicum) which you have read contains eugenol, both anti-inflammatory and antiseptic. But wait, another basil has a profile high in linalool or fenchol is used antiseptically. Another basil is high in methyl chavicol is more anti-flam than antiseptic. Extraction and distillation methods have dramatic effects on the chemistry and thus medicinal action. How could it be much different for any seed oil?How many purveyors of the product you seek are caring to pay for Nuclear Magnetic Resonance testing, Gas Chromatography, or Mass Spectroscopy when all the consumer has to know is it's label or a familiar smell?
From what we know about seed oils via Dr. Peat, I have my reservations about black seeds oil. Yes we know plant oils inhalation easily allows molecules through the blood-brain-barrier after processing. But, if the profile of the material is unknown, just what are you allowing through your BBB? Why dont they just include a GS reading on the label like an ingredients label? If someone asks me if I want salad, what does that mean? Potato salad? Shrimp salad? Word salad?
I still have questions about black seed extractions and cant see how an adequate measure of the compounds exist to qualify as a dose.
 

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@Nemo


In silico study of thymohydroquinone interaction with blood–brain barrier disrupting proteins

Fahad Hassan Shah, Saad Salman, Jawaria Idrees, Fariha Idrees & Muhammad Yasir Akbar

Published Online: 25 Sep 2020



...In the past few years, the pathology to drug discovery approach revealed promising new molecular drug targets that are highly efficacious and prevent [neurodegenerative] disorder onset. These molecular targets include human IFN-γ, IL-1β, TNF-α which incite an exaggerated inflammatory response by degrading the intricate basement membrane structure [23,25,26], resisitin destroys microvascular endothelial cells by oxidative stress and inflammation [24], VCAM-1 provides attachment sites to various immune cells and cytokines surrounding the barrier to degrade their tight junction [27] and MMP-9 instigates demyelination, amyloid plaques formation and digests microvascular structures leading to leaky and disrupted barriers [28]. These protein factors are recognized for the development of these disorders by damaging BBB endothelium and associated proteins and repairing cellular organelles causing irreversible colossal damage. Also, BBB leakage allows entry of various pathogens, toxins and other foreign entities along with immunoinflitration which further contributes toward neurodegeneration and onset of the neuropsychiatric disorders [8–11]. The deterioration of BBB is the primary indication of the development of these brain affecting disorders [4].

Several drug candidates are focused on targeting proteins that are present after or during BBB deterioration which may be involved in drug failure toward alleviating disease symptoms. On the other hand, several drug candidates have been proposed through virtual screening and molecular docking methods [34–36]. In these studies, the compounds show favorable interaction with the pathogenic proteins but possess low BBB and CNS permeability, high toxicity and adverse effects. Therefore, further interventions are required to counteract the adverse effects and deliver these drugs to visceral regions of the CNS.
...

The BBB is a protective element for the brain that acts as a partition between the brain’s blood vessels and glial cells and other components that constitute the brain tissue [12]. The BBB, therefore, provides a defense against disease-causing pathogens, neurotoxins and other foreign entities that are present in the blood plasma, while simultaneously allowing vital nutrients to reach the brain [6]. This barrier also maintains homeostatic hormone levels, nutrients and water in the brain to regulate its finely tuned environment. Structurally, the BBB is composed of a layer of endothelial cells which highly restrict the passage of substances from the blood [12]. As a result, the blood vessels that make up the CNS are defined as part of the BBB and are vascularized to tightly regulate the movement of ions, molecules and cells. The blood vessels and epithelial cells in the BBB communicate to change its selectivity, thus, minimizing the risk of brain infections and injury.

Instead of opting for the conventional method of targeting vital markers, the current study targets the proteins involved in deteriorating the BBB endothelium. These molecular protein markers increase BBB permeability by triggering the inflammation response, which causes immune cells and cytokines to infiltrate the barrier resulting in BBB endothelium degradation. The markers also upregulate other pathogen proteins to promote NNDs [neuropsychiatric and neurodegenerative disorders] onset [4,8–11]. These molecular targets revealed a new treatment strategy for NNDs; by inhibiting these targets, one can expedite BBB rehabilitation and possibly delay or prevent the onset of these disorders.

Thymohydroquinone is a multifaceted medicinal compound that has an astounding role in alleviating various types of NNDs by inhibiting lipopolysaccharides-induced learning, memory impairments and amyloid plaque formation as well as reducing oxidative damage and detrimental hippocampal cytokine levels [13]. This compound also plays a vital role in wound healing and tissue rehabilitation; [13] however, the role of thymohydroquinone in inhibiting BBB-pathogenic proteins and BBB rehabilitation are yet to be discovered. To evaluate the inhibitory interaction of this novel drug candidate, our study aimed to observe the interaction between thymohydroquinone and BBB-disrupting protein. An elaborated drug repurposing study was designed to determine the molecular inhibitory mechanism of thymohydroquinone against BBB-disrupting proteins.

Docking & stability analysis

...The interaction between thymohydroquinone and its target receptors were evaluated. These structures include human IFN-γ (1HIG), which disrupts tight vascular junctions [23], resisitin (1RFX) which contributes oxidative stress and inflammation and increases BBB endothelial permeability) [24], IL-1β (1T4Q) which augments BBB permeability and impairs astrocytes functions [25], TNF-α (1TNF) which disrupts tight junctions [26], VCAM-1 (1VSC) which provides attachment sites for cytokines and chemokines to induce inflammatory lesions [27] and MMP-9 (6ESM) which triggers neuroinflammation and degradation of BBB-regulating proteins [28]. These proteins are involved in the BBB structural integrity, resulting in neurodegeneration and onset of various neuropsychiatric disorders [8,9,29].

...It was observed that thymohydroquinone established a single hydrogen bond with the active site of the inflammatory proteins such as human IFN-γ, IL-1β and TNF-α, whereas double hydrogen bonds are formed with resisitin, VCAM-1 and MMP-9 (Figure 2). The active amino acid residues participated in hydrogen bond formation with the ligand were MET77, ASP81, TRP28 and TRP82, ALA115, GLU66, SER68, GLY186, and GLN227, respectively.

Thymohydroquinone protein receptors.png
[That table continues with more receptors below.]

...

Thymohydroquinone table 3 1.png

Thymohydroquinone table 3 2.png

[Notice oral bioavailability, BBB permeability, and CNS permeability.]
...

Discussion

...Medicinal plants contain several compounds that were exploited to rejuvenate mental and cognitive decline; most are BBB and CNS permeant and have low toxicity as evidenced by recent literature [37]. Thymohydroquinone is derived from the Nigella sativa plant, and is renowned for its myriad of biological activities, including neuroprotective and antidepressant effects [13]. However, the role of thymohydroquinone toward BBB-disrupting proteins is still obscure and was predicted in this article via molecular docking using Autodock 4.

...Pharmacokinetic analysis proved that thymohydroquinone is BBB and CNS permeable; its low toxicity and mutagenic properties indicate that is a promising candidate in the treatment of these disorders and might be useful in the rejuvenation of BBB.

Conclusion

All molecular drug targets including human IFN-γ, IL-1β, TNF-α, resisitin, VCAM-1 and MMP-9 demonstrated inhibitory interaction with thymohydroquinone by forming stable hydrogen bonds that prevented the targets from exerting their normal activity. Furthermore, this compound has high acute toxicity as analyzed through different administration routes with lower life-threatening side effects, which can be mitigated through nanocarriers. Thymohydroquinone has an efficient pharmacokinetic profile and could be the next promising single-drug candidate for the treatment and rejuvenation of these neurological anomalies. To our current knowledge, thymohydroquinone has multifaceted activity against these disorders which were assessed for the first time in this study and achieved efficacious results.

Future perspective

There is a strong need to develop rodent or human BBB models to study the effect of these pathogenic proteins and further corroborate the findings of the current study. This will allow the scientific community to investigate the effectiveness of thymohydroquinone in these models and determine whether could be used as a vehicle to understand drug pharmacokinetics and their therapeutic influence on BBB rehabilitation before subjecting it to clinical trials.

Summary Points

- The onset of neuropsychiatric and neurodegenerative disorders (NNDs) is related with the deterioration of blood–brain barrier (BBB) which is facilitated by five pathogenic proteins markers; human IFN-γ, IL-1β, TNF-α, resisitin, VCAM-1 and MMP-9, respectively.

- Thymohydroquinone is assumed to be active against different NNDs but has not been evaluated in BBB-associated NNDs.

- An elaborate drug discovery research was conducted, involving observations of molecular interaction and stability of thymohydroquinone with different BBB-deteriorating protein markers, acute toxicity, adverse effects and pharmacokinetics of this ligand were predicted.

- Our study revealed that thymohydroquinone is a potent inhibitor of the BBB-disrupting proteins and show adequate interaction with all molecular targets responsible for BBB-associated NNDs.

- This compound possesses appreciable binding and ligand efficiency with a promising inhibitory constant value.

- It possesses BBB and central nervous system permeability with a high acute toxicity profile.

- The rare adverse effects associated with thymohydroquinone are hepatotoxicity, arrhythmia and cardiac failure.
 

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