Plant Cuttings

This image of baskets of plants that may – or may not – be sources of natural medicines, taken by an anonymous photographer, is free of copyrights under Creative Commons CC0.

Plants are a resource that has long been exploited by people in many ways. Arguably, their most ancient – and enduring – use is in providing humans with ‘the four Fs of ethnobotany’ – food, fuel, fibres, and pharmaceuticals (which latter category is broad and includes sources of plants as medicines – that make us better, and drugs – that may make us feel ‘better’). Covering all of those interactions would make for a very long post. This Cutting will therefore focus on the pharmaceutical potential of plants (Liji Thomas; Deborah Lee; Jennie Gwynn and Peter Hylands). However, some of the items covered will also have relevance to one or more of the first three categories of ‘the four Fs’. And to demonstrate that, the first item concerns a plant that combines fibres, medicines, drugs, and food…

Cannabis and consumption

This image, entitled “An array of Nestle Munchies candies”, by Evan-Amos is made available under the Creative Commons CC0 1.0 Universal Public Domain Dedication.

Cannabis sativa (Antonino Pollio, Cannabis and Cannabinoid Research.Dec 2016.234-238; http://doi.org/10.1089/can.2016.0027; Susanne Schilling et al., Current Biology30: R8–R9, 2020) has a number of English common names, depending on the use to which it has been put by people. As a plant that has supplied fibres – for making clothing, paper money (Hazey Taughtme), ropes with which to hang people (but apparently not to make the material upon which the United States’ Declaration of Independence and Constitution were written) – it is known as hemp (Melissa Petruzzello). As a provider of drugs – whether for ‘recreational’ purposes (e.g. as ‘pot’ or hash) or medicinal uses (e.g. as cannabis oil, cannabidiol [CBD (Kimberly Holland)] – it is known as marijuana (Sian Ferguson; Melissa Petruzzello). Those multiple uses are down to recognition – and human-assisted development – of different varieties of the same species (Melissa Petruzzello), with differing concentrations of the psychoactive substance tetrahydrocannabinol [THC (Kimberly Holland)] (Sian Ferguson; Mary Jo DiLonardo & Jennifer Walker-Journey; Melissa Petruzzello).

Concentrating on the drug use of the plant here, a phenomenon associated with smoking marijuana is known as ‘the munchies’. That behaviour is so-called because those who use marijuana often feel the need to eat [to munch upon food] after – and maybe during – taking the drug. On the basis that ‘where there’s something to be investigated, somebody, somewhere, will investigate it’, Emma Wheeler et al. (Sci Rep 13, 22970 (2023); https://doi.org/10.1038/s41598-023-50112-5) have done just that. Although they worked with mice rather than human volunteers, they discovered that inhalation of marijuana vapour [the equivalent of the smoke internalised by a human user of the product] “increased meal frequency and food seeking behavior”, but “without altering locomotor activity [“a term to describe the general movement of a organism or object from one area to another” (N Sam)] (Lisa Lightner)”. This findings are the first to investigate how cannabis impacts the real-time activity of brain regions that control appetite (Carly Cassella), and “support an abundance of anecdotes and rigorous studies on humans, which all strongly suggest smoking, vaping, or eating cannabis can trigger acute cravings and have you headed for the pantry or fridge in no time”.

If relatable to humans*, this study suggests that, although those who use marijuana and succumb to the munchies would eat, they’d expend minimal energy in acquiring the food. Therefore, the net effect of frequent cannabis use would appear to be that users would put on weight, an unintended consequence of their ‘hobby’. In which case they might be interested in the next item…

For more about the science behind this work, do look at the article by Carly Cassella.

Celastrol and weight-loss

This image of lump sugar cube on black background by Marco Verch is licensed under Creative Commons 2.0

Whilst eating more food than the body needs – e.g. whilst experiencing the ‘munchies’ [see previous item on marijuana] – can lead to weight-gain, some plants can help us lose weight** This item concerns one such plant-derived ‘anti-obesic’ [don’t Google it, it is a new word created by Mr P Cuttings to describe a pharmaceutical product that acts against obesity] compound, celastrol (Rita Cascão et al. (2017). Front. Med. 4:69; doi: 10.3389/fmed.2017.00069; Jinfeng Shi et al. (2020). Front. Pharmacol. 11:558741; doi: 10.3389/fphar.2020.558741). Celastrol is one of many compounds found in the root of Tripterygium wilfordii, a plant with a long history of use in traditional Chinese medicine [TCM] to treat fever, psoriasis, and arthritis (Fermin Koop). The plant, which has the memorable common name of ‘thunder god vine’***, has also been used to treat obesity, which is where the celastrol comes in (e.g. Junli Liu et al., Cell 161: 999–1011, 2015; http://dx.doi.org/10.1016/j.cell.2015.05.011).

However, although useful as an anti-obesity treatment, the root-derived extract – that contains the cerastrol – is a cocktail of compounds that is toxic to humans. Unless prepared and administered properly, you’re likely to lose more than just weight if taking this ‘medicine’. And this often Nature’s way: Although She may provide the medicine, we need to do our bit to wrest those beneficial compounds from the rest. A method of separating the medicinally-valuable ‘wheat from the chaff’ is therefore needed if the benefits of celastrol are to be gained. And that’s what Yong Zhao et al. (Nat. Chem. 15, 1236–1246, 2023; https://doi.org/10.1038/s41557-023-01245-7) have come up with.

Using yeast (Saccharomyces cerevisiae), they were able to reproduce the multiple enzyme-controlled steps that lead to the synthesis of celastrol. This so-called semi-biosynthetic method has several advantages over extracting the celastrol from the plant. In particular, it produces the active chemical free from contamination with toxic compounds. But, it also ensures reliability and consistency over the natural source whose celastrol content varies from root batch to batch, and which also depends upon how the root is treated after harvest.

Somewhat ironically, the biosynthetic method developed by Yong Zhao et al. (2023) produces celastrol from table sugar (sucrose) – ingestion of which natural plant product is notoriously associated with weight gain and obesity in humans (Samir Faruque et al., Pol J Food Nutr Sci. 69(3): 219-233, 2019; doi: 10.31883/pjfns/110735). Success is – sometimes – sweet?

For more on this work, see the scicomm piece here, here, and the article by Fermin Koop.

Cancer-prevention, and -treatment, with beans?

This image of Phaseolus vulgaris, white beans by Rasbak is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license.

We humans eat foodstuffs primarily as a source of energy (Nicole Avena) – by virtue of the calorific content (Yvette Brazier) of the plants (and animals) that we consume. Almost as an unexpected bonus of that consumption, many compounds in the plants we eat have medicinal value which help to keep us healthy (Heather Alexander; Mrinal Samtiya et al., Foods 2021, 10, 839; https://doi.org/10.3390/foods10040839).

Take, for example navy beans (Phaseolus vulgaris), which are also known as haricot beans, Boston beans, Yankee beans, and pea beans, etc., etc. (Sylvia). Eaten by humans for hundreds (Sylvia) – if not thousands (Sunmin Park et al., Journal of Ethnic Foods 3: 171-177, 2016; https://doi.org/10.1016/j.jef.2016.08.001) – of years, they provide – amongst other nutrients – a good dietary source of protein, carbohydrates, fibre, and essential minerals such as iron, magnesium, calcium, phosphorus, potassium****. Now, in 2024, an additional reason to eat navy beans relates to their likely role in cancer-treatment and/or its prevention.

Work by Xiaotao Zhang et al. (eBioMedicine 2023; 98: 104873; doi: 10.1016/j.ebiom.2023.104873) has shown that consumption of navy beans may benefit obese survivors of colorectal cancer. Amongst the benefits identified were an increase of ‘beneficial bacteria’ and a decrease in pathogenic, or opportunistic, bacteria. Beans generally, but navy beans in particular, “are full of gut-supporting fibers (Zhi-Wei Guan et al., Molecules. 2021 Nov 11;26(22):6802; doi: 10.3390/molecules26226802), amino acids, and other nutrients, which can help the beneficial bacteria in your colon flourish, supporting immune health and regulating inflammation”, explained Carrie Daniel-MacDougall (last-named and corresponding author of the study whose comments are cited here).

Taken together, these positive changes in the participants’ gut microbiome (Ruairi Robertson), which are associated with cancer prevention and improved treatment outcomes, are a most encouraging result from this trial, which is part of the optimistically, if rather forcedly, acronymed study known as BE GONE [Beans to Enrich the Gut microbiome vs. Obesity’s Negative Effects] (Xiaotao Zhang et al., BMC Cancer 19, 1233 (2019); https://doi.org/10.1186/s12885-019-6400-z).

Although this dietary intervention was specifically targeted at survivors of colorectal cancer, one wonders if regular consumption of navy beans as part of a healthy individual’s diet might be advantageous in preventing the condition? Or, whether those who regularly partake of navy beans are less likely to suffer from such diseases? If so, that would be another reason to eat navy beans – in addition to their other documented health benefits (Sylvia), and a bonus that bean-eaters have already benefited from/enjoyed*****.

For more communication of the science behind this work, see here, and here, and the articles by Abigail Brooks, and Elana Gotkine.

Corona virus-killing willow

This image of aspirin pills by Daniel Foster is provided under the Attribution-NonCommercial (CC BY-NC 2.0) licence.

There can be few people reading this post who haven’t heard of the long-established connection between willow-tree bark and pain-killing aspirin******. Taking that medicinal willow-bark further, Dhanik Reshamwala et al. (2023) (Front. Microbiol. 14:1249794; doi: 10.3389/fmicb.2023.1249794) demonstrate that it also has anti-viral properties. Using hot-water-extracts of willows – specifically clones (Henry Owen]) of dark-leaved willow (Salix myrsinifolia Salisb.) and tea-leaved willow (S. phylicifolia L.), and their hybrid (S. myrsinifolia x S. phylicifolia) – they showed that it has virucidal activity against enveloped coronaviruses, and non-enveloped enteroviruses. Coronaviruses notoriously are responsible for the recent COVID-19 pandemic (Luke Powles), MERS [Middle East respiratory syndrome], and the common cold. Enteroviruses cause infections such as meningitis (Rebecca Cantu & Joe Das), pneumonia (Whitney Sinclair & Manal Omar), and poliomyelitis [polio] (Whitney Sinclair & Manal Omar). And enteroviruses also include rhinoviruses, and enterovirus D68 (Scott Lawrence), which has been called the “new polio” (Hayley Cassidy et al. Front Microbiol. 2018 Nov 13;9:2677; doi: 10.3389/fmicb.2018.02677).

Altogether these viruses are a pretty ‘bad bunch’ from a human perspective. Anything that can be exploited in the battle against them to keep humans healthy and well is to be welcomed. Although Reshamwala et al. didn’t investigate all of those viruses, they did specifically study the virus that causes COVID-19 and a sample of other coronaviruses and enteroviruses. To cut a fascinating, but quite long and technical study short, willow-bark extracts were found to have “excellent antiviral potential against the non-enveloped enteroviruses … and … were equally effective against the seasonal and pandemic coronaviruses”, halting infection by both.

Which all sounds most encouraging. But, as with most medical studies there are a few caveats. The study was undertaken in a laboratory with “human alveolar basal epithelial adenocarcinoma (A549), Vero E6, and human lung fibroblasts (MRC-5) cells”, i.e. not with human participants. It is a long way from demonstrating anti-viral activity in a lab on cell cultures to developing an effective virucidal agent for more general use in the environment, or people. Any effectiveness of the extracts in a more realistic setting has yet to be investigated. At present the active compound, or compounds, in the bark extract has yet to be established. Isolating all of the compounds, and testing each of them, will be a necessary but time-consuming task. Although the single Salix species and the natural hybrid tested were shown to have the virucidal activity, it was much less pronounced in the artificial hybrid created by crossing (S. myrsinifolia x S. phylicifolia) with S. gmelinii. The reasons for variability between species, hybrids, and clones will need to be assessed to find the most effective ones, for consistency and reliability of production of the active ingredient(s). Salix is a big genus – with “around 350” to “over 400” (Stephen Harris] species. So far only two species have been examined. Although Reshamwala et al’s results are encouraging, it would be nice to see investigation extended to all Salix species to see if any of those are even more effective at producing the virucidal activity. Alternatively, as with the celastrol item above, identifying the active compound might enable its more ready-synthesis in a non-willow system such as yeast. Lots to do. But also lots at stake. And, it should be noted – and as Reshamwala et al. recognise – that the willow extract is not envisaged as a replacement for vaccines, but represents an additional weapon in the arsenal being deployed in the war against viruses.

For other scicomm accounts of this work, see here, and articles by Paul McLure, John Anderer, and Sergio Prostak.

* Interestingly, in Wheeler et al‘s study, “vaporized cannabis plant matter” “was administered passively to rodents”. I.e. the mice weren’t directly smoking ‘joints’. But, the fact that passive contact with cannabis smoke had the effect of increasing meal frequency causes Mr Cuttings to wonder if this is something that could be exploited by unscrupulous businesspeople. Could those who sell unhealthy snacking food release ‘vapourised cannabis plant matter’ outside their premises to generate food-seeking behaviour in passers-by that would encourage people to pop into the shop and purchase the purveyor’s products? On the basis that, ‘if you can think it, somebody, somewhere is probably already doing it’, this makes you wonder. Maybe that is already a part of the business model/strategy behind Amsterdam’s famous ‘coffeeshops’ (Derek Robertson et al.)? Hmmm, maybe, but for more marijuana-musings, you must look elsewhere.

** In reference to the preceding item, it’s worth mentioning here that recreational and prescription cannabis is commonly used to address appetite issues, e.g. those relating to eating disorders or chemotherapy (Carly Cassella).

*** Another of the plant’s common names is ‘seven steps to death’, a reference to how many steps one might take after consuming an improperly prepared extract before dying (Fermin Koop). The plant is therefore one to characterise under the MM category (for ‘murderously medicinal’)…

**** For all the health-giving benefits of beans – including navy, a note of caution is needed. Famously beans contain phytohaemagglutinin, which is toxic to humans. Fortunately, its toxicity is all but eliminated if the beans are properly cooked – but not in a slow-cooker (Suzanna Sandridge) – before consumption (Nick DeSimone; Christine Ruggeri).

***** That beans – and therefore the health benefits thereof (Sylvia) – aren’t as common in the diets of modern-day North Americans has been ascribed to the well-known ‘gasogenic effect’ of their consumption. That is to say, in the vernacular, beans make you ‘fart’, or ‘pass gas’, or ‘break wind’. In more polite language, they cause ‘flatulence’. For more on this phenomenon, have a look at the research article by Donna Winham & Andrea Hutchins (Nutr J 10, 128 (2011); https://doi.org/10.1186/1475-2891-10-128). And remember, “you’re never too old to laugh at farts”… Putting that behind us, and on a more serious ‘note’, for more on the history of beans, in particular what’s described as a “swift pop culture history”, do have a look here]. And, for intriguing insights into “the symbolism of navy beans in art and iconography”, there’s Kristina Billan’s essay.

****** If that’s you, items here, here, here, and articles by Philippa Martyr, Dawn Connelly, Jane Moon, and Joe Schwarcz will get you up to speed.