if we found an interesting results in antidiabetic activité (in vivo) of a plant extract, potent than a known drug, what should we do in the next step of the investigation, we already knows the major constituentsof the extract
I think that firstable, there is no limit for in vivo studies. There is preliminary pharmacological evaluation, however we can develop interesting model to elucidate the effect against insulin resistance, mithocondrial functionality, genes expression, biological markers and membrane receptors direclty linked to diabetes. Also we can choose to fractionnate the extract and test the main fractions regarding their phytochemical content.
Also we can use a functional test for bioguided isolation to find some interesting molecules with high activity.
But i will suggest if the material is interesting to test different extracts (Polysaccharides, Oil, Essential oil, Organic extracts, Fibres...) before you search for the active principles
There is also the ratio between therapeutic/toxicity and it will be interesting to find high activity in the vegetable oil fraction wich is maybe less toxic..
You can also associate diabetes to many pathophysiological status, such as hypertension, diabetes complications like nephropathy and neuropathy and eye diseases...also oxidative stress and inflammation
It depend on what you focus on : diabetes or plant or both of them
But i will suggest bioguided isolation of active principales and in vitro elucidation of the mechanism under cellular conditions for exemple hepatic and pancreatic cells
thank you Ilias Marmouzi for your answer, it's really interesting
I already know's the chemical composition (the major constituents) and two of them were reported as antidiabetic molecules. The data suggest that these metabolites improved the severely dysregulated adiponectin expression in diabetic rats, probably thus leading to a reversal of the altered activities of key metabolic enzymes in liver and ultimately producing an improved glucose homoeostasis. another research on the same compounds demonstrated that these flavones promote adipocyte differentiation and glucose uptake by inducing PPARγ activation and then modulating the insulin-signalling pathway in some way, which could benefit diabetes patients
Your work is very interesting. I think if you already know the major molecules, you should focus on minor compounds, especially derivatives from those molecules. Maybe you will find new compounds with enhanced activity.
Working in cell culture and isolated or in situ pancreas models may be exciting to understand the mechanism of action. Meanwhile, studies for the purification and the isolation of active compound(s) will be necessary.
Although I have cell culture lab in our dept, I do not have an experimental setup for this purpose. However, with a little effort, it may be possible to test some of major compounds in our lab.
If I understand you correctly you have identified and characterized novel substances that have an effect on blood glucose when administered to an animal model. My next steps would be to better understand the PK/PD profile, dose response and roughly estimate the NOAEL. With this information I would evaluate the toxicology profile in formal GLP studies with feedback from your national regulatory agency on design such that the toxicology work could support a first in human clinical trial.