Aconitine induces mitochondrial energy metabolism dysfunction through inhibition of AMPK signaling and interference with..., 2021, Yang et al

Andy

Andy

Senior Member (Voting rights)
Full title: Aconitine induces mitochondrial energy metabolism dysfunction through inhibition of AMPK signaling and interference with mitochondrial dynamics in SH-SY5Y cells.

Abstract

Aconitine, a highly toxic alkaloid derived from Aconitum L., affects the central nervous system and peripheral nervous system. However, the underlying mechanism of aconitine-induced neurotoxicity remains unclear. This study investigates the effects and mechanism of aconitine on mitochondrial energy metabolism in SH-SY5Y cells. Results demonstrated that aconitine exposure suppressed cell proliferation and led to an increase in reactive oxygen species (ROS) and excessive lactate dehydrogenase (LDH) release. Aconitine (400 μmol/L) induced abnormal mitochondrial energy metabolism that quantified by the significant decrease in ATP production, basal respiration, proton leak, maximal respiration, and succinate dehydrogenase (SDH) activity. Phosphorylation of AMPK was significantly reduced in aconitine-treated SH-SY5Y cells. The AMPK activator AIACR pretreatment effectively promoted ATP production to ameliorate mitochondrial energy metabolism disorder caused by aconitine. Mitochondrial biosynthesis was inhibited after treatment with 400 µmol/L aconitine, which was characterized by mitochondria number, TFAM expression, and mtDNA copy number. Moreover, aconitine prompted the down-regulation of mitochondrial fusion proteins OPA1, Mfn1 and Mfn2, and the up-regulation of mitochondrial fission proteins p-Drp1 and p-Mff. These results suggest that aconitine induces mitochondrial energy metabolism dysfunction in SH-SY5Y cells, which may involve the inhibition of AMPK signaling and abnormal mitochondrial dynamics.

Paywall, https://www.sciencedirect.com/science/article/abs/pii/S0378427421001193
 
Why was this research necessary? Is there a poisoners' handbook available that I've never heard of?

According to the Wiki article on aconitine : https://en.wikipedia.org/wiki/Aconitine

Consuming as little as 2 milligrams of pure aconite or 1 gram of the plant itself may cause death by paralyzing respiratory or heart functions.[23] Toxicity may occur through the skin; even touching the flowers can numb finger tips.[23]
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The reference given is to this link :

https://www.drugs.com/npp/aconite.html

Apparently it gets used in homeopathy.
 
I think the fact that all authors are at the University of Traditional Chinese Medicine, and aconite is apparently something used in TCM, is the reason why this was looked at.

I posted it because I thought that the evidence for these kind of effects might be of some interest to anybody looking at the mitochondria in ME, however I'm not trying to suggest that we are all suffering from aconite poisoning ;)
 
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Kitty said:
I've grown it for decades, I love it – as do bumblebees, as the plants produce a lot of nectar.

It rarely needs handling anyway, but it's easy enough to wash your hands afterwards. Quite a lot of the crowfoots are toxic to some degree or other.
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Note the risk if you handle it if you have a cut. And I was wondering that if it is such a potent poison, what might be its (possibly cumulative) effect in much smaller doses? Could the study have relevance to that?
 
Barry said:
And I was wondering that if it is such a potent poison, what might be its (possibly cumulative) effect in much smaller doses?
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You'd have to be ingesting it, though, in order to get a dose in the first place – there's no chance of a cumulative effect if you don't. People know to wear gloves and wash their hands after gardening, as there are toxins in everything from rhododendrons, to daffodils, to laburnum, to foxgloves. Water hemlock might even be more dangerous than monkshood, and it's a not uncommon weed.

Plant poisoning is really unusual in the UK. You're probably a lot safer growing an entire garden full of the most toxic species you can find than travelling in a car!
 
Kitty said:
You'd have to be ingesting it, though, in order to get a dose in the first place – there's no chance of a cumulative effect if you don't. People know to wear gloves and wash their hands after gardening, as there are toxins in everything from rhododendrons, to daffodils, to laburnum, to foxgloves. Water hemlock might even be more dangerous than monkshood, and it's a not uncommon weed.

Plant poisoning is really unusual in the UK. You're probably a lot safer growing an entire garden full of the most toxic species you can find than travelling in a car!
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From what I've read you don't necessarily have to ingest it. If you have a cut and it gets into your blood you can get into trouble.

And I'm afraid people like me don't normally have a clue. I'm tuned into this wavelength here, but I'm just not wired up to remember plant info. My wife is eternally patient with my complete inability to remember what plant is what. People like you and my wife know, but people like me are plant illiterate. Not for the want of trying, but I can never remember what they are in the garden, apart from the obvious ones.

And my point still is: How would you know if you were getting mild cumulative poisoning or not, if the symptoms developed over time and were ME/CFS-like?
 
Barry said:
And my point still is: How would you know if you were getting mild cumulative poisoning or not, if the symptoms developed over time and were ME/CFS-like?
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You can't ingest it without touching it. Toxins aren't going to get through rubber gardening gloves, either. I planted mine when I moved here three years ago and haven't handled it since; in my last garden, I probably last broke up the clump to give some to my neighbour about 10 years previously. It's a perennial, so it just dies down every winter and regrows in the spring. As with most of my garden, I just leave it to get on with it, as I haven't the energy for needy plants!

The average gardener couldn't give you a list of poisonous plants and trees, as it's enormously long. It's further complicated by the fact that some parts of edible plants are also rather toxic, such as the nightshades (potatoes, tomatoes). I think I was about four when my granddad gave me the 'wear gloves, don't rub your eyes, wash your hands' talk. The fact that it's not at all difficult to avoid harm from plants is illustrated by the fact that serious incidents are very rare.


ETA: There was a row of laburnum trees outside our infant school, the seeds of which are extremely poisonous, so we got the lecture there, too!
 
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