Well, that certainly suggests that acute toxicity is not a problem under ordinary conditions.
But that is the kind of thing that usually would already be well-known about a botanical which has as long a history as this one does.
That study is one that I find a bit worrisome. The same researcher is cited in most of the studies that show efficacy over the past decade, which is not a good sign when coupled with the observation that other labs seem to not always reproduce those results.
There is tissue culture work that seems to reflect G-coupled receptor signalling up-regulation (and down-regulation, fwiw)... but that system is so complicated that it's hard to say what else is happening as a result.
There are a lot of feedback loops in whole organisms surrounding that signalling pathway. If you tweak one side of it, the whole raft moves, basically, and there's no way to shut off that connectedness.
Renin-angiotensin is another one like that, which is why I look at any agent that purports to have cardiotonic or hepatotonic benfits and think... Hmmmm... really? So what else is it doing, then? Ohhh.... nobody has looked. GREAT. (Not.)
Agents that act in the renin-angiotensin pathway have a tendency to do things downstream that work on the cardiac muscle receptor subtypes for a whole host of ligands. For example, I mean.
Many of the kinds of things that I worry about here are the sorts of things that eventually result in black box warnings on pharmaceuticals, or lead to them being pulled off the market. Mostly its related to unintentional downstream effects that are intrinsic to the class of molecules. The COX-2 inhibitors are a good example, as is a drug like Avandia.
The things that I really stay away from are those that seem-- really-- too good to be true. That's because I know in my heart of hearts that nothing is really that effective AND that 'clean' and that the truth is probably that they just don't (yet) know what it is doing otherwise.
Elidel is a great example of one of those.
The thing that freaks me out about herbals as a class is that the majority of them are like those drugs. Only partially elucidated mechanisms, no real idea about dosage (because you can't quantify something if you don't even know what it is) and a lack of long-term safety data. Ethnobotany has a real problem in collecting safety data for traditional remedies; the reason is that in traditional herbal practice, it was very likely that a condition which was serious enough to require intervention was: a) already life-threatening to start with, so little additional harm in trying other approaches, and b) already treated in a variety of other non-allopathic ways. So if a person dies after treatment with Ma Huang, there's little to suggest that it wasn't the asthma that did them in, and the threshold for establishing that something is "risky" long-term is VERY VERY high, because in the traditional cultures where such medical practice developed, life-expectancies weren't that great to begin with, and "long term" might mean something different than it does to modern first-world residents.
It's worth recalling that Coca was initially greeted with many of the same-- in fact, the EXACT same-- support and claims as Rhodiola; improvement in stamina, "balancing" neurotransmitters, better focus and concentration, sense of well-being, etc. etc. There is a lot of hand-waving surrounding the pharmaceuticals which impact the biogenic amine neurotransmitter systems, too-- but I'm suspicious of ALL of those claims on the basis of what I know about that system. ALL of them come as a package deal with permanent changes in neurotransmitter kinetics, and induce dependence, and the reason is that the two parts of the molecules that seem to do those things... overlap. No way to separate them.
Same red flags for dirty pharmacology here, too. In other words, I'm suspicious that it seems to do too many different things that have little to do with one another at the molecular scale. It has to be a cocktail if it's really doing that stuff. If it's a cocktail, then that increases the risk that it's doing something harmful.
