Talk:Artemisinin

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Biosynthesis

The contributions to the biosynthesis of artemsinine are excellent, I find. For my part, my extensions are short and to the point. It is important to create new links to every wikipedia entry. This is done in the spirit of wikipedia. But, I agree, it might appear as too simplistic but yet, usable for those who read it. —Preceding unsigned comment added by 81.62.47.252 (talk) 01:28, 12 February 2011 (UTC)[reply]

The Keasling/Amyris process is presented in C Paddon et al, Nature, 2013, DOI: 10.1038/nature12051 . Please add that reference to this useful and comprehensive article.216.73.192.204 (talk) 21:52, 29 June 2014 (UTC)[reply]

Mechanism of action

I would be grateful if this area could be monitored by experts and / or experienced Wikipedia users.

The evidence that artemisinins kill parasites by acting on redox metabolism relating to the parasite digestive vacuole is mounting, while evidence against PfATP6 being the site of action is diminishing as more tests of that hypothesis are published. Recently the group advocating that PfATP6 is the target of artemisinins published a substantial Corrigendum in Nature that clearly reduces confidence in the original publication. My edit in which I tried to point this out was effectively reversed by a new edit which suggested that an updated analysis '...has confirmed the original observations' and the clear labelling of this as a Corrigendum was removed. In the revision history the contributor Gmelins explains that 'A more balanced interpretation of a recently published paper (Uhlemann2012) is presented'. To reiterate, Uhlemann2012 is not an original paper but a Corrigendum to a 2005 paper, and no one reading the Corrigendum could conclude that it confirms the original observations; as I said above it could only undermine confidence in the findings from this system, rendering it even more vital that readers should look to other authors and commentators to shed light on the area.

And the evidence from elsewhere is that PfATP6 now appears very unlikely to be linked to artemisinin action. For example, in their paper from February 2012, Cui et al., who are independent of those originally promoting the hypothesis, conclude: 'Collectively, the evidence accumulated thus far strongly suggests that PfATP6 does not have much to do with ART resistance'. I have therefore made a further edit to reflect this. This edit also shortens the section considerably (it had become extremely wordy, particularly for an area that appears increasingly to be irrelevant to this drug's mechanism of action) and provides, in my view, a succinct and neutral summary appropriate to this important field.

It would be helpful for readers if biologists could review this section from the perspective of Wikipedia's statement on neutral point of view. Further input into the other sections of the article is also urgently needed.

Many thanks Uamha (talk) 12:39, 19 March 2012 (UTC)[reply]

The views expressed in the first 2 paragraphs above reflect a highly partisan view. A full synthesis of the PfATP6 SERCA hypothesis, has after peer review been recently published[1]. It addresses all the points made in the above (including erroneous comments regarding the parasite's food vacuole as a target for artemisinins) and below paragraphs, and provides reanalysis of the Cui paper that is consistent with artemisinins acting on parasite SERCAs. More recent results are from an independent and robust yeast model (not as confounded above with a corrigendum on a separate paper), and these are simply ignored. Furthermore, judging by the nature of critiques put forward, it is unlikely that the contributor has usefully worked directly on these hypotheses, or is current and familiar with all the literature on the subject.

References

--— Preceding unsigned comment added by 194.82.50.2 (talkcontribs) 13:50, 27 November 2014 (UTC)[reply]

Synthesis section

All those parenthetical numbers are pretty much useless without accompanying structural drawings, but the paragraph was unfortunately written in such a manner as to preclude simply removing them. The section needs a rewrite so that it's no longer dependent on the parentheticals, or it desperately needs a set of structural drawings of the compounds referenced. IMO, this would probably be more useful than the immediately preceding drawing of the biosynthetic (mevalonate) pathway, especially in light of the way the total synthesis is described.64.134.179.130 (talk) 00:19, 29 December 2012 (UTC)[reply]

PARTLY  Done I have rewritten the synthesis section, adding secondary citations, and a couple newer primary ones. It is still in need of a figure, but I am not convinced that the early Schmid design is the best; perhaps two are needed, the first and the best, so at present, it remains without an image (but cum better text, and sans numbers). Le Prof Leprof 7272 (talk) 09:05, 19 June 2014 (UTC)[reply]

History section opening sentences and overall section tagged for need of citations and some poorly formatted material moved here to Talk

The first two paragraphs of the History were poor when I arrived, and I have tried to improve their readability, and their adherence to WP policies. The two paragraphs were combined, with material from the second ("herb" sentence) placed at an appropriate point in the first paragraph.

Then, there was a later sentence in the section whose English was unreadable, and whose citations were in a format so as to be unverifiable. That sentence has been corrected, thus:

  • "Images of the original scientific papers that record the history of the discovery have been available online since 2006."

and it remains in the article in this edited form.

Next, the citations that appeared with this sentence are unverifiable for various reasons, and are so poorly formatted as to be disruptive to reading. They are therefore moved here to Talk, for the record, and for holding until they can be corrected (REF2) or replaced (REF1 and REF3):

Disallowed as a blog posting. Not an acceptable source. Also a bare URL. SOURCE MUST BE REPLACED.
  • REF2 (BOOK) Zhang Jianfang (2007) Late Report: Record of Project 523 and the Research and Development of Qinghaosu, Yangcheng Evening News Publisher [Chinese citation: 張劍方 (2007) 遲到的報告五二三項目與青蒿素研發紀實, 羊城晚報出版社]
May be acceptable, if details can be clarified: Corrections needed are page numbers of information cited, and ISBN or some other unique identifier so book can be sourced. SOURCE MUST BE CORRECTED.
Disallowed as a bare URL and as an apparent broken link. Link takes one to an all Chinese page. SOURCE MUST BE REPLACED.

There is a further redacted reference, from the sentence introducing Tu Youyou:

This is a BLP issue, as this is a curriculum vitae of a living person, based on unspecified Chinese and English web sources, and so it is unclear as to its independence and accuracy. (E.g., sources may include unreliable or self-published information.) Citation also appeared as a Bare URL. SOURCE MUST BE INVESTIGATED FOR PROPRIETY.

Per WP policies, full, standard forms of citations are needed, all the more if the source is rare and/or hard to source. Please do not return these four until the indicated issues are resolved. (Reversion of this edit without change will bring in an administrator.)

Note, REF1 and REF4 are enjoyable and interesting reading, but REF1 is just not a valid source for Wikipedia, and REF4 must be confirmed as reliable, broadly, at WP. Le Prof Leprof 7272 (talk) 06:33, 19 June 2014 (UTC)[reply]

I found some references that are related to the discovery and madical use of artemisinin. Both Chinese and English versions of paper are included in the reference list. Many of those are relatively original research paper of artemisinin, which gave us better idea on the early history of artemisinin in the scientific field. References: 1.Collaboration Research Group for Qinghaosu(1977). A new sesquiterpene lactone—qinghaosu [in Chinese]. Kexue Tongbao 3, 142 http://www.kjdb.org/CN/article/downloadArticleFile.doattachType=PDF&id=13117

2.Xiao, Y.Q. & Tu, Y.Y. (1984) Isolation and identification of the lipophilic constituents from Artemisia anomala S. Moore [in Chinese]. Yao Xue Xue Bao 19, 909–913. http://en.cnki.com.cn/Article_en/CJFDTotal-YXXB198412005.htm

3.Collaboration research group for Qinghaosu(1979). Antimalarial studies on qinghaosu [in Chinese].Chin.Med.J.92,811–81 https://www.cabdirect.org/cabdirect/abstract/19802901722

4.Liu, J.M. et al. (1979) Structure and reaction of qinghaosu . Acta Chimi. Sin. 37, 129–143 . http://www.cnki.com.cn/Article/CJFDTotal-HXXB197902005.htm

5.Tu, Y. (2011). The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine.Naturemedicine,17(10),1217. https://www.nature.com/articles/nm.2471.pdf?origin=ppub

6.Miller, L. H., & Su, X. (2011). Artemisinin: discovery from the Chinese herbal garden. Cell, 146(6), 855-858. https://doi.org/10.1016/j.cell.2011.08.024

7.Huang, L. et al. Studies on the antipyretic and anti-inflammatory effects of Artemisia annua L [in Chinese].Zhongguo Zhong Yao Za Zhi 18, 44–48 (1993). http://en.cnki.com.cn/Article_en/CJFDTOTAL-ZGZY199301025.htm

8.Sun, X. Z. (1991). Experimental study on the immunosuppressive effects of qinghaosu and its derivative. Zhong xi yi jie he za zhi= Chinese journal of modern developments in traditional medicine, 11(1), 37-8. https://europepmc.org/abstract/med/2054892

9.Youyou, T. (2004). The development of the antimalarial drugs with new type of chemical structure-qinghaosu and dihydroqinghaosu. Southeast Asian journal of tropical medicine and public health, 35(2), 250-251. http://www.thaiscience.info/Journals/Article/TMPH/10601625.pdf

10.Zhang, D., Yang, L., Yang, L. X., Wang, M. Y., & Tu, Y. Y. (2007). Determination of artemisinin, arteannuin B and artemisinic acid in Herba Artemisiae Annuae by HPLC-UV-ELSD. Yao xue xue bao= Acta pharmaceutica Sinica, 42(9), 978-981. https://europepmc.org/abstract/med/18050742

---Yliu3089 (talk) 18:02, 21 February 2019 (UTC)[reply]

Cancer

Dear Wikipedia:

Hello;

Concerning the Wikipedia article on Artemisinin - at https://en.wikipedia.org/wiki/Artemisinin

the important FDA approved Malaria herb/drug does not discuss Artemisinin as an anti cancer drug, why ?

( Adding this information my save or prolong the lives millions of persons affected by cancer. )

Please see Artemisinin as a Cancer Smart Bomb, Part I and 2 :

at http://www.mwt.net/~drbrewer/canart1.htm and http://www.mwt.net/~drbrewer/canart2.htm and http://www.mwt.net/~drbrewer/FreeCanArtimisUpDate.htm

Quote from Link:

Artemisinin Cancer Smart Bomb, Part I: An Idea from Ancient Chinese Medicine


this paper and others can be found at:

http://www.mwt.net/~drbrewer/FreeCancerArts.htm


" The anti-cancer activity of artemisinin against 55 cancer cell lines was tested in the N.C.I.'s (National Cancer Institute) Developmental Therapeutic Program. Artemisinin was found to be most active against leukemia and colon cancer cell lines. Most promising was artemisinin's strong activity against drug resistant leukemia lines. Other cancer cell lines tested that indicated some responsiveness to artemisinin's actions were melanoma, breast, ovarian, prostate, renal and central nervous system cancers such as glioblastoma and neuroblastoma. ("The anti-malarial artesunate is also active against cancer," International Journal of Oncology, 18 {2001} 267-773) "

http://www.mwt.net/~drbrewer/canart1.htm

(c) 2002 Brewer Science Library, All rights reserved Excerpted from New Horizons, Summer 2002 issue


article attached

I researched anti worm drugs / agents as cancer drugs as I have stage 4 colon cancer.

    Please notice most anti worn parasitic medications also have anti cancer properties. see   your article on the antihelmintic drug Mebendazole at: https://en.wikipedia.org/wiki/Mebendazole  see  https://pdfs.semanticscholar.org/0109/c133ae30079fe21948f85e8c12466b10a903.pdf and the shocking before and after 6 wk photos..( still not a cure ) ( article attached  )

Could Wikipedia please update the Article on Artemisinin an FDA approved treatment for Malaria to reflects its anti cancer properties ? — Preceding unsigned comment added by Dizzo2361 (talkcontribs) 20:01, 17 April 2018 (UTC)[reply]

Thanks but sources about health need to be OK per
WP:MEDRS and mwt.net is not OK. I will look to see if there are reviews on this drug and cancer... Jytdog (talk) 05:51, 18 April 2018 (UTC)[reply
]
There is a decent recent review; I added some content about that here. Jytdog (talk) 06:21, 18 April 2018 (UTC)[reply]

Mechanism of action 2

" The malaria parasite enters the red blood cells and sequesters iron. The mechanism of action of artemisinin in "zapping" the malaria parasite is through the affinity of artemisinin to iron. The artemisinin compound contains two oxygen atoms hooked together in what is termed an endoperoxide linkage. In the presence of free iron this linkage breaks down, forming very reactive free radicals that cause rapid and extensive damage and death to the parasite. "

Source Artemisinin a Cancer Smart Bomb, Part I: An Idea from Ancient Chinese Medicine http://www.mwt.net/~drbrewer/canart1.htm — Preceding unsigned comment added by Dizzo2361 (talkcontribs) 01:07, 18 April 2018 (UTC)[reply]

As above, mwt.net is not OK per MEDRS. Jytdog (talk) 06:21, 18 April 2018 (UTC)[reply]


Reference 6 is incorrect

Relating to artemisinin's advantages over other therapeutics. Having looked at the reference, it seems to be a different subject, with no mention of either malaria, plasmodium or artemisinin. If anyone is working on this page and can get to the bottom if it, would be most appreciated, if not, I'll take a look in due course.

 TobyBrann 17:59, 26 January 2021 (UTC)[reply]
  • Agreed. No mention of any of those three, or the plant species. With this citation being used for such specific claims it really makes me wonder why. I suggest just going ahead and removing, and if this is the only cite then {{citation needed}}. Invasive Spices (talk) 23:43, 26 January 2021 (UTC)[reply]

Did Tu really discover it?

It seems over hyped to claim in the article that she is the first person in the world to discover this compound. She was probably the first person to name it in the modern sense but not the first person to discover or come across the compound and realise its beneficial effects. Ancient Chinese TCM herbalists have already long been using the same low temperature extraction methods for hundreds of years in treatment of Malaria. She merely rediscovered it after following instructions from an ancient TCM book.[1] To claim she discovered it, is just like claiming Christopher Colombus had discovered America despite obviously native Americans' ancestors beat him to it. Both claims are absurdly ignorant of actual history. Nvtuil (talk) 20:58, 22 October 2021 (UTC)[reply]

Cell differentiation

Hello @Zefr: I don't work in medicine so I didn't even think that my phrasing would sound medical. As for in vitro this is actually in vivo for rodents and I had thought that would be obvious but you only know that if you read the review, read the paper, and figure out which part I'm talking about. In my mind this was not meant to be medically relevant but instead I was adding in this text to be definitive as to only that particular dynamic, i.e. cell differentiation in rodents. If there's any further human medical relevance that was not for me to say. But in actual fact I didn't say that in the text.

Anyway since you did that I gathered up all the other cites for this and it's a huge number[1][2]Cite error: A <ref> tag is missing the closing </ref> (see the help page).[3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] in addition to the two I already had.[19][20] Since I went through all those I noted that in fact Shin fails to replicate in non-human primates and Krentz[16] thinks that's important. I interpret that to mean they believe this will never work for any primate. Overall this much coverage does tell us that this is an important controversy. Would you be satisfied to add in some text about "has only been found rodents and most importantly Shin finds this does not work in non-human primates which may be fatal for hopes of human use"? Invasive Spices (talk) 17 March 2022 (UTC)

As we edit Wikipedia to be an encyclopedia, not a journal article covering what's emerging from lab research,
WP:MEDREV, we should wait until a reputable review in the mainstream medical literature (not from traditional Chinese medicine) summarizes what is new and significant about artemisinin beyond what the article states now. Zefr (talk) 22:44, 17 March 2022 (UTC)[reply
]
You didn't read what I wrote. What is this a reply to? Invasive Spices (talk) 18 March 2022 (UTC)
What I see in your comments and weak TCM and lab references above is a diffuse unfocused discussion that is
WP:OFFTOPIC about artemisinin. If you can find an actual reputable review to include, and offer a draft of text, then we can consider your proposal specifically. Zefr (talk) 17:06, 18 March 2022 (UTC)[reply
]
Where did I say anything about TCM? Which references do you think are relevant to TCM? Which references do you think are "lab references"? Which reviews do you think are not reputable? Invasive Spices (talk) 18 March 2022 (UTC)
Refs 1-20 and 22 are from lab research in vitro and in vivo. A review of lab research is still a reference about lab research too preliminary for use in an encyclopedia. #21 is based partly on TCM - anytime the word "magic" is in an article's title, we should dismiss the source as dubious. At least 17 of the 22 refs imply importance to diabetes, which is not mentioned in the article; caution is needed about overinterpretation and
WT:MED. Zefr (talk) 20:22, 18 March 2022 (UTC)[reply
]
Just chiming in to partially agree with Zefr. Not everything that is true of a topic should be in a Wikipedia article on that topic. Artemisinin is known for many things: miraculously potent antimalarial, lovely example of a drug sourced to traditional medicine, unusual chemical scaffold, a pain-in-the-ass to synthesize, etc. These are basically always covered in reliable sources on the topic. The fact that some artemisinin derivatives may cause alpha cells to act funny in immortalized rodent cells is just not that important to the story of artemisinin. This specific example seems to be on particularly poor footing - the Nat Rev End review only brings it up to shoot it down, and the original paper has apparently attracted some controversy (though I don't subscribe to the The Scientist magazine, so I'm inferring the contents from the title and first two paragraphs). But even if it was an uncontested finding, I still think any mention would be out of
WP:PROPORTION to its importance. Ajpolino (talk) 01:55, 19 March 2022 (UTC)[reply
]
You both have been arguing with a strawman so long I can't possibly lose! You'll both be too tired to continue. Good for me.
Seriously: We all need to move back away from medical claims I have not made. The text does not make any medical claims and as I said above I was surprised Zefr thought that because I did not mean to. I am interested to change the text as necessary so that is clearer if there are medical claims in my text that I am unaware of. Specific replies:
  • A review of lab research is still a reference about lab research too preliminary for use in an encyclopedia. I don't understand. A review about lab research is
    WP:SECONDARY
    . This is normal to use yes? Is this something about medical citations I am unfamiliar with, because just to repeat, we need to get away from the idea that this is medical.
  • #21 is based partly on TCM None of Wang is based on TCM. It does provide one paragraph and half of another paragraph of historical context. The other eight pages are science from 1971 and later. This is an Elsevier journal after all. The text I am citing is Recent findings have even identified a remarkable—if controversial—role of artemisinin in diabetes through inducing transdifferentiation of pancreatic a cells to generate b cells [142,143]. [142] = Li and [143] = van der Meulen.
  • anytime the word "magic" is in an article's title, we should dismiss the source as dubious. A fanciful title is used because artemisinin has become so familiar that it is safe to do so. This is commonly done. For introducing a new substance or receptor this would look ridiculous yes.
  • At least 17 of the 22 refs imply importance to diabetes, which is not mentioned in the article Yes? I agree? I did not mention diabetes. caution is needed about overinterpretation and
    WP:SYNTH
    .
    We do not need to be careful about overinterpreting things that we are not interpreting at all. If I have mentioned diabetes and then forgotten I did so please point out where it is.
  • WT:MED
    would be inappropriate because again the effects of artemisinins on rodents are not necessarily relevant to humans, and even more specifically in this case are looking very doubtful for human purpose.
  • The fact that some artemisinin derivatives may cause alpha cells to act funny in immortalized rodent cells is just not that important to the story of artemisinin. Twenty two reputable reviews think otherwise. And note, this is in vivo or should I say in rodentia (and in Li, in transzebrafish).
  • This specific example seems to be on particularly poor footing - the Nat Rev End review only brings it up to shoot it down Yes several reviews endorse it, endorse it as correct along with other results which are contradictory = these are all correct for different combinations of substances and targets, or shoot it down in that way. and the original paper has apparently attracted some controversy Yes several of my sources treat this as controversial. That does make it a very large controversy worth covering.
Note again that Krentz[16] specifically doubts that this will ever work for non-human primates (in other words all primates) and I note that Pacios-Michelena[21] also has some doubts about human relevance. I intended to present this as a very widely attended rodent matter and I will try to present a revised text to that effect tomorrow. Invasive Spices (talk) 19 March 2022 (UTC)

I'm sorry to repeat myself, but I still think this doesn't merit mention. Best I can tell, this is the kind of incident that happens in laboratory science all the time: group A published a paper claiming a surprising finding; other groups fail to replicate, or extend it to other research models; life goes on. Perhaps the material would be germane to an article on

undue. Ajpolino (talk) 23:44, 19 March 2022 (UTC)[reply
]

Yes my joke was not entirely accurate. You do bring up a good point that normally a failure to replicate is not notable. However I think we need to take our idea of what is DUE or UNDUE from these 25 (
WP:DUE
, fairly represent all significant viewpoints that have been published by reliable sources, in proportion to the prominence of each viewpoint in the published, reliable sources. and Keep in mind that, in determining proper weight, we consider a viewpoint's prevalence in reliable sources). (Also keep in mind that when I wrote the first version I had read only Wang, Xu et al., 2019 and Nair et al., 2020. Then I read the others and this went from settled, different results for different substances to massive controversy. So I've changed my position to cover the controversy.)
Here is my proposal:
There is much controversy as to the effects of various artemisinin derivatives on
GABA in rhesus macaque, although GABA is not an artemisinin but has a related action.)[13][14][16] Both Eizirik & Gurzov 2018[10] and Yi et al., 2020[13] consider it possible that these are all legitimately varying results from varying combinations of substance, subject, and environment. On the other hand a large number of reviewers[4][5][6][9][10][11][12][24][15][21] are uncertain whether these are seperate effects, instead questioning the validity of Li on the basis of Ackermann and van der Meulen – perhaps GABA receptor agonists as a whole are not β-cell-ergic.[4][11] Coppieters et al., 2020 goes further, highlighting Ackermann and van der Meulen as publications that catch an unreplicatable scientific result, Li.[25]
I think this supports the notability of the range of expert opinion well. Because this is specific to several of the artemisinin family, I don't think this would be appropriate to cell development articles although maybe. Moreso, that is not a subject where I can contribute very much, although if someone else created such articles it's possible I could contribute this small part. Invasive Spices (talk) 21 March 2022 (UTC)
I think we're not likely to come to agreement on this. It would be helpful if others chimed in so we can reach some kind of consensus. I'm guessing no one else is really watching this page, so I've posted at
WT:MED and WT:Molecular Biology to see if anyone else might be willing to share their thoughts. Ajpolino (talk) 21:18, 24 March 2022 (UTC)[reply
]
concur w/ Invasive spices (above)...please remember {{citation overkill}}--Ozzie10aaaa (talk) 13:00, 26 March 2022 (UTC)[reply]
I forgot that bundling is even possible. I will fix that in the next version. Invasive Spices (talk) 28 March 2022 (UTC)
I was going to wait a week and ping Zefr and yourself but WP:MolBio is fine. I have to again note that MED is not going to be related here because these are rodent and Danio dynamics and because (after I looked further) I found these several other sources saying that these effects have not/will not hold for primates. Invasive Spices (talk) 24 March 2022 (UTC)
Hi, for disclosure I saw the mention of this discussion at WT:MED. First off, congratulations for pursuing this discussion on the talk page and not with editing the mainspace. Invasive Spices you have clearly done extensive reading into this area and I can see that your edits have improved the article. However, I agree that this particular topic and your proposed paragraph is too esoteric to be included in this article, as it really does constitute small print even in a specialised review article. Most of the references fail ]
@Spaully: Which are primary? Invasive Spices (talk) 25 March 2022 (UTC)
I'll strike the point on primary literature so as not to get drawn into a discussion on highly specific review articles, I think the central point stands and I don't have the time or interest to get drawn into a longer discussion. I suggest the best outcome for this is to find or write a more specific article which it pertains to, such as the suggestions by Ajpolino above. I won't be expending further energy on it. |→ Spaully ~talk~  16:38, 27 March 2022 (UTC)[reply]
Ozzie10aaaa objects to my horrible citations (one of which takes up most of the page width) but otherwise supports this version, Ajpolino doesn't want this here at all, Spaully same but won't push, which leaves Zefr. Sorry to bother you again but you were very certain I was making medical claims and I didn't understand that anyone would think that. Have I gotten away from confusion with medical claims and towards animal effects only? Should this be here, because it pertains to the artemisinin family, or elsewhere? Or do you still think this isn't worth having at all? Invasive Spices (talk) 28 March 2022 (UTC)
Not going to repeat the assessments I made above about lab research being included in the article where the emphasis is on its antimalarial properties which led to a 2015 Nobel Prize, demonstrating its notability. Your draft proposal is convincing enough about uncertainty that the status of understanding on cell differentiation is speculative at best. As no reviews of lab research clarify this content adequately in an encyclopedic way, and there is no consensus from editors in this discussion to include anything like your draft, I suggest you drop the topic. If future research clarifies the issue, talk page history and your list of sources can serve then as the basis for new discussion. Zefr (talk) 20:49, 28 March 2022 (UTC)[reply]