The crux of this is that nothing exists in isolation. Humans evolved eating plants and plants evolved trying not to be eaten so a large part of human physiology

The crux of this is that nothing exists in isolation. Humans evolved eating plants and plants evolved trying not to be eaten so a large part of human physiology is probably designed to deal with plant toxins. Any natural product that is potent but gentle is probably just short of being dangerous, it's certainly nothing to do with being not being manufactured. A quick search for dangerous herbs gives a decent list of plant which can have catastrophic effects if eaten. The scientific approach is attempting to unravel all this but we are only at the beginning and it's going to take a long time to figure it all out.