Guest post Research integrity

The curative plant extracts from Allahabad

Meet Danish Ahmed and other members of the Sam Higginbottom gang. I am not making those names up.

Aneurus Inconstans wrote a story about fraudulent Ayurveda research from Allahabad, India. The plant extracts, of course from traditional Indian plants featuring in Vedic medicine or at least in Indian cuisine, are presented as cures for diabetes, cancer and many other diseases, and of course they are best deployed on nanoparticles. A number of these fabricated papers appeared in the journal BMC Complementary Medicine and Therapies, Springer Nature’s special outlet for Ayurveda, Traditional Chinese Medicine and other quackery from paying customers (€2040 a pop).

Allahabad, that brings fond memories. The home town of Ashutosh Tiwari, Sweden-based research fraudster and a surprisingly tenacious organiser of scamferences (predatory conferences), and even a heart surgery business (currently in India only).

There is no evidence the cheaters of the following story ever met Tiwari or bought phony awards and medals from his phony IAAM yet, but he will sure offer a rebate to his fellow Allahabadians!

Tiwari (left) with his scamference partners in Allahabad. Source: Facebook.

But now, over to Aneurus Inconstans. You can also meet him on PubPeer exposing research fraud, and here his previous guest post on For Better Science:


The curative plant extracts from Allahabad

By Aneurus Inconstans


The Sam Higginbottom University of Agriculture, Technology and Sciences (SHUATS) is a government-aided university located in Allahabad, India, “serving the nation for the past 111 years”, as the caption on the website states. The Department of Pharmaceutical Science at SHUATS has been very productive in the past years, in particular regarding three of its faculty members: associate professor Danish Ahmed, assistant professor Vikas Kumar, and professor Amita Verma.

These people are serving the nation by churning out articles full of questionable data (to say the least), which are mostly about the allegedly beneficial effects of plant extracts for the treatment of diabetes, dermal wounds and carcinogenesis in rats. Mind you, these “research articles” are often published with respected publishers (whatever that means), and their “data” could potentially lead to the commercialization of those phyto-products infused into pills, tablets and ointments for “curing” people and cashing in, if only these compounds were patented. Twenty-one papers from the Department of Pharmaceutical Science at SHUATS, showing the most serious concerns you can imagine, have been flagged in PubPeer as of today.

Let’s start from Ahmed et al. 2015 SpringerPlus:

Danish Ahmed*, Vikas Kumar, Amita Verma, Girija Shankar Shukla, Manju Sharma*. Antidiabetic, antioxidant, antihyperlipidemic effect of extract of Euryale ferox salisb. with enhanced histopathology of pancreas, liver and kidney in streptozotocin induced diabetic rats SpringerPlus (2015) doi: 10.1186/s40064-015-1059-7

In Figure 10 three panels showing the effects of Euryale ferox seeds extract (KEFx) or Glibenclamide (KGLIM) on the histological profile of rat kidney overlap with images published a year before in Figure 10 of Ahmed et al. 2014 BMC Complement Altern Med., where the effects of Albizia lebbeck stem bark extract (ALEx) on the same kind of tissue are described instead. There’s also an overlap within Figure 10 of the 2014 article, between the control NKALx and the image of STZ-induced diabetic rats treated with ALEx at dose of 200 mg/kg body weight (KAL200). More overlapping micrographs are present between Figure 8 and 11 of the respective papers, where the histological profile of rat liver upon same treatments are shown, and again between Figure 9 and 2 on the histological profile of rat pancreas:

Danish Ahmed*, Vikas Kumar, Amita Verma, Pushpraj S Gupta, Hemant Kumar, Vishal Dhingra, Vatsala Mishra, Manju Sharma* Antidiabetic, renal/hepatic/pancreas/cardiac protective and antioxidant potential of ethanol/dichloromethane extract of Albizzia Lebbeck Benth. stem bark (ALEx) on streptozotocin induced diabetic rats BMC Complement Altern Med (2014) doi: 10.1186/1472-6882-14-243

Images have been cropped differently, rotated and resized. Of note, SpringerPlus is a journal that (maybe luckily) ceased to be published by Springer Nature as of June 2016.

An author, who did not disclose their identity, replied on PubPeer on these issues:

Sir, thank you for your query. As this research work was a combined effort, it is possible that an unintentional error might occur that time. Kindly find below the correct images of LEFx-100 and LGLIM below. Sincere apologies for this unintentional error […] As the above images of Kidney are treated with the two different extracts to the group of rats and the experiment was conducted parallelly there are chances of unintentional error. Kindly find below the image of PEFx300. Sincere apologies for this unintentional error. Regards”.

Here are the images posted by the author:

new image of LEFx-100 provided by anonymous author
new image of LGLIM provided by anonymous author
new image of PEFx-300 provided by anonymous author

Unfortunately the new image provided for LGLIM was already published in Ahmed et al. 2015 J Food Sci Technol as the control (NLIV) for rat liver treatement with 2β-hydroxybetulinic acid 3β-caprylate (an active principle from Euryale ferox seeds), which had allegedly antidiabetic, antioxidant and hepatoprotective properties:

Danish Ahmed*, Manju Sharma*, Vikas Kumar, Harish Kumar Bajaj, Amita Verma 2β-hydroxybetulinic acid 3β-caprylate: an active principle from Euryale Ferox Salisb. seeds with antidiabetic, antioxidant, pancreas & hepatoprotective potential in streptozotocin induced diabetic rats J Food Sci Technol (2015) doi: 10.1007/s13197-014-1676-0

The other two images are obviously cropped portions of bigger micrographs that nobody could predict what they really are. Ahmed et al. 2015 J Food Sci Technol in turn shares a myriad of micrographs with the previously mentioned Ahmed et al. 2015 SpringerPlus:

Danish Ahmed, corresponding author of the papers described so far, declared on his LinkedIn profile that he also worked at the World Health Organization (WHO) as senior research scientist for seven months (Aug 2008 – Feb 2009).

We all wonder what Ahmed’s tasks at WHO were, let’s hope his stay wasn’t long enough to do damage, or maybe this employment was just as real as Ahmed’s science?), but if not: a shiver might now run down your spine, dear reader, at what kind of people do science at WHO. The best kind.

The second co-corresponding author is Manju Sharma, associate professor at Jamia Hamdard, an institute of higher education “deemed to be university” located in New Delhi.

By the way, the Sharma Lab produced this beauty on its own, without any helping hands from SHUATS people this time:

Yam Nath Paudel, Md Rahmat Ali, Mohammad Adil, Sandhya Bawa, Manju Sharma* “2-(4-Fluorobenzamido)-4-methylthiazole-5-carboxylic acid” a novel thiazole compound, ameliorates insulin sensitivity and hyperlipidaemia in streptozotocin-induced diabetic rats: Plausible role of inflammatory and oxidative stress markers Biomed Pharmacother (2017) doi: 10.1016/j.biopha.2017.09.014

Fig. 9. Histopathological evaluation of Liver. Photomicrograph of sections of liver tissue of normal group (A), STZ-control group (B), STZ+ NDTD (10 mg/kg) treated group (C), STZ+ NDTD (20 mg/ kg) treated group (D), per se NDTD (20 mg/kg) treated group (E) and STZ+ pioglitazone (10 mg/ kg) treated group (F). Images at 100X.

Two samples were used to describe six different conditions. Images were resized and modified in colour.

Let’s go back to SHUATS, this time to Vikas Kumar‘s Lab, here the problematic data are about the curative properties of Paederia foetida leaf extracts. Same technique used in New Delhi, images showing different treatments are stretched horizontally to look different:

Vikas Kumar*, Firoz Anwar, Danish Ahmed, Amita Verma, Aftab Ahmed, Zoheir A Damanhouri, Vatsala Mishra, Pramod W Ramteke, Prakash Chandra Bhatt, Mohd Mujeeb* Paederia foetida Linn. leaf extract: an antihyperlipidemic, antihyperglycaemic and antioxidant activity BMC Complement Altern Med (2014) doi: 10.1186/1472-6882-14-76

Lots of micrographs in Figure 4, 7, 10 and 11 of this article were published a year before in Figure 19, 26, 23 and 24 respectively of Kumar et al. 2013 BMC Complement Altern Med, that describes the beneficial effects of umbelliferone β-D-galactopyranoside from Aegle marmelos, a rare species of tree from India whose leaves, bark, roots, fruits, and seeds are used in traditional medicine to treat various illnesses, although there is no clinical evidence that these methods are safe or effective:

Vikas Kumar*, Danish Ahmed, Amita Verma, Firoz Anwar, Mohammed Ali, Mohd Mujeeb* Umbelliferone β-D-galactopyranoside from Aegle marmelos (L.) corr. an ethnomedicinal plant with antidiabetic, antihyperlipidemic and antioxidative activity BMC Complement Altern Med (2013) doi: 10.1186/1472-6882-13-273

Figure 11 of Kumar et al. 2014 BMC Complement Altern Med also includes three micrographs published a year before in Figure 22 of yet another paper, Kumar et al. 2013 SpringerPlus, which also describes the phenomenal effects of umbelliferone on glycemic control, and on liver and pancreas protection:

Vikas Kumar*, Danish Ahmed, Firoz Anwar, Mohammed Ali, Mohd Mujeeb* Enhanced glycemic control, pancreas protective, antioxidant and hepatoprotective effects by umbelliferon-α-D-glucopyranosyl-(2(I) → 1(II))-α-D-glucopyranoside in streptozotocin induced diabetic rats Springerplus (2013) doi: 10.1186/2193-1801-2-639

The keen observers among you may note that BMC Complementary and Alternative Medicine is a frequent title showing up here, published by Springer Nature. This journal changed its name in BMC Complementary Medicine and Therapies starting in 2020.

The co-corresponding author, together with Vikas Kumar, of the previous two papers is Mohd Mujeeb, assistant professor at Jamia Hamdard.

The following articles are collaborative works with Firoz Anwar, an Indian professor working abroad at King Abdulaziz University in Jeddah, Saudi Arabia, who already co-authored many articles described so far, and Imran Kazmi, associate professor at Glocal University in Saharanpur, India. This time the topic is the synergistic effects of ibuprofen and thiamine (vitamin B1) on the significant reduction of hepatic nodules in rats. In Figure 2 of Afzal et al. 2017 Arch Biochem Biophys (an Elsevier journal), three micrographs have been taken from a paper published two years before in Khan et al 2015 RSC Advances. An untreated liver control was previously described as liver treated with Loparamide (blue boxes), an ibuprofen-thiamine control was previously described as liver treated with Niacin (yellow boxes), and DEN ibuprofen-thiamine control was as untreated liver control (cyan boxes). Images have been all resized and colours have been changed:

Muhammad Afzal, Imran Kazmi*, Ruqaiyah Khan, Poonam Rana, Vikas Kumar, Fahad A Al-Abbasi, Mazin A Zamzami, Firoz Anwar* Thiamine potentiates chemoprotective effects of ibuprofen in DEN induced hepatic cancer via alteration of oxidative stress and inflammatory mechanism Arch Biochem Biophys (2017) doi: 10.1016/j.abb.2017.05.006

Ruqaiyah Khan, Imraan Kazmi, Mohd Afzal, Fahad A. Al Abbasi, Mushtaq Gohar, Aftab Ahmad, Vikas Kumar*, Firoz Anwar* Fixed dose combination therapy loperamide and niacin ameliorates diethylnitrosamine-induced liver carcinogenesis in albino wistar rats RSC Adv (2015) doi: 10.1039/c5ra11201j

RSC Advances is published by the Royal Society of Chemistry, UK, and it seems its articles started to be indexed in PubMed from 2017 only.

I asked for clarifications to Dr. Kumar (and to all others at SHUATS) via email before this article in For Better Science was published, in order to give them the chance to explain. This is Dr. Kumar’s answer to me:

“Dear sir. Greetings of the day.  Thanks for highlighting the issue and sorry for the delay in response.  However it is to bring to your kind notice that this issue was raised by one of our senior author and we have already communicated to the journal regarding the histopathology of figures. The clarification is attached below. We are concerned with clarification of our manuscript [singular?? – A.] and not others.  Thanks for your concern. Regards. Sincerely yours”

Attached was the text of Kumar’s email exchange with Pauline Starley, research integrity advisor at Springer Nature, typos his:

“Dear Sir, Thanks for your mail. And hope my mail will find you in the best of your health and cheerful mood. This is mail is with respect to the above cited subject, I would like to bring at your kind notice that authors were aware of such discrepancies’ in the histopathological figures of our accepted manuscript in 2016 and recently one of our senior Professor and coauthor of manuscript along with rest of authors have brought this to the notice of the journal and same was rectifies by sending the erratum. The major reason for this error was due to lack of histopathological facilities in our department and non-expertise in this part of work (Research). The histopathological work was not done in our department and all the work regarding this was outsourced. [highlight mine – A.] Hence, we terminated the contract with the lab and technician involved in preparing and processing the slides. Though as a record for safety we kept the blocks of tissues for five years and were available with us before COVID 19 pandemic. No such problem had aroused from the last couple of years. Since the spingureplus [SpringerPlus – A.] joumal is discontinued now we cannot make any changes in it. If any further discrepancies are observed at your end in such photographs kindly intimate us .We will try to rectify it. Sorry for the inconvenience. Thanking you. Regard”

For brevity I didn’t include here Ms. Starley’s email (Dr. Kumar attached it as a PDF file to me), but this answer doesn’t make any sense. First of all, apparently Ms. Starley queried about two articles published in 2013 and 2014, not in 2016 (Kumar et al. 2013 SpringerPlus, and Kumar et al. 2014 BMC Complement Altern Med), secondly it’s bizarre to argue a paper cannot be “changed” just because the journal ceased to be published. However, it’s interesting to know that the histological data was outsourced. Are we facing a “papermill” here?

In another PDF sent to me by Dr. Kumar, it seems he requested an erratum in June 2020 to the disastrous Kumar et al. 2016 BMC Complement Altern Med (not discussed here, I spare you that). Was the answer to Springer referring to that erratum request? Is Dr. Kumar aware he published eight papers at Springer, all of them worth of retraction, and that people are querying many of them, not just one?

Several other articles from Allahabad on yet other compounds and treatments are showing micrographs of rat liver, pancreas and kidneys that have been resized, squeezed, stretched, and reused to describe different things in yet other papers. But let’s now jump onto the topic of dermal wounds, again treated with plant extracts. An avalanche of duplications (or different takes of the same wound) are recognizable within and between Figure 3 and Figure 5 of these two articles:

Ekta Yadav, Deepika Singh, Pankajkumar Yadav*, Amita Verma* Ameliorative effect of biofabricated ZnO nanoparticles of Trianthema portulacastrum Linn. on dermal wounds via removal of oxidative stress and inflammation RSC Adv (2018)  doi: 10.1039/c8ra03500h

Ekta Yadav, Deepika Singh, Pankajkumar Yadav*, Amita Verma* Attenuation of dermal wounds via downregulating oxidative stress and inflammatory markers by protocatechuic acid rich n-butanol fraction of Trianthema portulacastrum Linn. in wistar albino rats Biomed Pharmacother (2017) doi: 10.1016/j.biopha.2017.09.125

Have these dermal wounds images been also outsourced?

Many of those wounds are shared in Yadav et al. 2018 Biomed Pharmacother too, where the plant extract is from Prosopis cineraria instead of Trianthema portulacastrum. Co-corresponding author of these dermal wounds articles is Pankajkumar Yadav, associate professor also at the Department of Pharmaceutical Science at SHUATS.

Ekta Yadav, Deepika Singh, Pankajkumar Yadav*, Amita Verma* Antioxidant and anti-inflammatory properties of Prosopis cineraria based phenolic rich ointment in wound healing Biomed Pharmacother (2018) doi: 10.1016/j.biopha.2018.09.180

The Verma lab has many expertises actually, they even engage in scanning electron microscopy (SEM). Here the same SEM micrograph shows embedded silver nanoparticles of Carissa carandas (CCAgNPs) and Phyllantus emblica (PEAgNPs) in two different papers:

Deepika Singh*, Deepak Chaudhary, Vikas Kumar, Amita Verma* Amelioration of diethylnitrosamine (DEN) induced renal oxidative stress and inflammation by Carissa carandas embedded silver nanoparticles in rodents Toxicol Rep (2021) doi: 10.1016/j.toxrep.2021.03.014

Deepika Singh*, Ekta Yadav, Neha Falls, Vikas Kumar, Manvendra Singh, Amita Verma* Phytofabricated silver nanoparticles of Phyllanthus emblica attenuated diethylnitrosamine-induced hepatic cancer via knock-down oxidative stress and inflammation Inflammopharmacology (2019) doi: 10.1007/s10787-018-0525-6

[Read here and here about the journal Toxicology Reports and its Editor-in-Chief, Aristidis Tsatsakis- LS]

The authors claim CCAgNPs ameliorate renal oxidative stress and carcinogenesis induced by N-diethylnitrosamine due to their antioxidant and anticancer activities. Same properties are ascribed to PEAgNPs against hepatocellular carcinoma. Carissa carandas is a flowering shrub whose berries are commonly used in India as a condiment to dishes, while Phyllanthus emblica is a tree whose fruits are edible and used in traditional Indian medicine (Ayurveda). Co-corresponding author of these two articles is Deepika Singh, who also seems to be a faculty member at SHUATS, although the Department of Pharmaceutical Science does not list her name currently.

Another mix-up between Carissa carandas and Phyllanthus emblica nanoparticles images, but this time is transmission electron microscopy (TEM), between the above mentioned Singh et al. 2019 Inflammopharmacology and another paper published in IET Nanobiotechnology (a Wiley journal):

Deepika Singh, Vikas Kumar, Ekta Yadav, Neha Falls, Manvendra Singh, Ujendra Komal, Amita Verma One-pot green synthesis and structural characterisation of silver nanoparticles using aqueous leaves extract of Carissa carandas: antioxidant, anticancer and antibacterial activities IET Nanobiotechnol (2018) doi: 10.1049/iet-nbt.2017.0261

Creative Dr. Verma’s achievements have been celebrated in a lovely interview available on YouTube:

From this video we learn Dr. Verma was awarded a travel grant by the American Chemical Society (ACS) to present a research paper at the 2018 Pittcon Conference in Orlando, Florida (at 20 min 15 sec), she received travel support by the Science and Engineering Research Board (SERB) Govt. of India to attend the 2018 Joint Prague-Weizmann Winter School on Drug Discovery in Rehovot, Israel (at 20 min 25 sec), and 30,000 USD from the National Institute of Health (NIH) Office of AIDS Research (OAR) for doing research on “designing and evaluation of long acting conjugates as anti-HIV-1 agents” at Chapman University, California, US, in 2018 (at 21 min 08 sec).

Final remarks

It’s not in question whether all this money (including the Article Processing Charges and the salaries of all the people involved here) wouldn’t be better allocated differently, but it’s probably more important that no-one gets fooled with phantom and unrealistic alternative remedies based on these “data” to cure serious illnesses.

Twenty-one articles (not all discussed here) from the Department of Pharmaceutical Science at SHUATS would deserve consideration for retraction. Sixteen of them include Vikas Kumar, 14 Amita Verma, 10 Danish Ahmed, then all the others. However, this is just the proverbial tip of the iceberg, as mostly PubMed indexed articles have been checked, and each person here reported did publish tens (if not hundreds) of smaller papers in little journals with impact factor between 2 and zero-something currently not indexed by NCBI. Additionally, most of the articles analysed had data of histograms and tables only, for which it’s a lot more complicated to spot data manipulation.


10 comments on “The curative plant extracts from Allahabad

  1. Outrageous as this publication crapfest may be, I suspect the therapeutic impact will be minimal. Turns out that in phase II trials most of the subjects given these preparations came down with a terrible case of the shuats.

    Like

  2. The amount of junk papers published like this make it absolutely difficult to find any actually important lead molecule for therapeutic application.

    Like

    • Don’t worry about that. Real drug research is done by the pros in the pharmaceutical industry labs. Stuff that gets published in this field is mostly worthless and ignored. That’s why they can get away with such nonsense. It’s all pretend.

      Like

  3. Wait, why is there a guy with a GUN on a scholarly conference meeting? Also, is this boom in traditional medicine part of the nationalist agenda of Indian government?

    Like

    • The building in the background belongs to Tiwari’s father, who runs a law school diploma mill there. Junior uses same building as VBRI institute. Why the gun? Maybe to make sure the customers pay the fees?
      Yes. PM Narendra Modi is a Hindu Fascist with an Ayurveda fetish. There’s even an AYUSH Ministry (look it up)

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  4. Here another answer from another protagonist of this story, Firoz Anwar, again referring to one single manuscript (without saying which one), while this guy has 8 papers flagged on PubPeer:

    Dear Mr. Aneurus ( Hope this is the name only)
    Greetings of the day
    Thanks for the notifying the error in the manuscript.
    This issue was already taken up by me and was informed to journal. i have already contacted the other authors on said issue and discussed . If error is there it will be rectified through the journal.
    Thanking you
    Best Regards:

    Prof. Firoz Anwar
    Ex Dean Siddhartha Institute of Pharmacy
    Dehradun-248001- Uttarkhand,

    Like

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  6. Two more flagged papers in PubPeer for Verma, Kumar and Anwar:

    https://pubpeer.com/publications/7B856B983C04B75B760716499B728A

    https://pubpeer.com/publications/5C9630775A183C5BC7FE1741829BDE

    In Figure 3 of Verma_et_al_2017_Inflammopharmacology, five out of six tumor images (colored boxes) were used a year before in another paper by the same group (Verma_et_al_2016_Inflammopharmacology) where treatments were completely different. Images are identical, just resized vertically.

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  7. Yet another problematic paper for Firoz Anwar and his lab, published in that appalling title named “Saudi Journal of Biological Sciences”:

    https://pubpeer.com/publications/DAF689FF8C1E54539D340E83C71928

    Like

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