This study was posted over in another thread in ageless looks. It's from 2007 though, surely there's more progress since this effort to inhibit HNE began.
It appears that HNE builds up over time. Its normal function is to break down foreign proteins but apparently due to a number of factors. For instance, there are endogenous inhibitors of HNE (alpha-1-antitrypsin, elafin, and the secretory leukocyte proteinase inhibitor) that in younger people act as a control on these enzymes. Here is why:
Large quantities of oxidants and proteases released by leukocytes that are recruited to the site of inflammation can inactivate these endogenous inhibitors. Moreover, tight adhesion of neutrophils to the ECM leads to the compartmentalization of the released proteases between the neutrophil and the ECM, thereby excluding the large, circulating protease inhibitors. Tight binding of extracellular HNE to the cell membrane can render it inaccessible to circulating endogenous inhibitors. Altogether, the imbalance between HNE and its inhibitors caused by these events provokes severe tissue injuries resulting in a variety of diseases.
HNE starts breaking down elastase in an out of control sort of way. Once again inflammation is at the root.
It has become clear that serine proteases, such as HNE, have an important regulatory role in the local inflammatory response. Thus, its dysregulation resulting in its accumulation can be involved in the development of chronic inflammatory diseases, such as rheumatoid arthritis, pulmonary emphysema, adult respiratory distress syndrome (ARDS), cystic fibrosis, COPD, asthma, and delayed wound healing.
Rather than find exogenous inhibitors, why not attempt to free and enable the endogenous ones by addressing the root of the problem? If uncontrolled elastase leads to all these diseases from arthritis to emphysema to slower wound healing, and our bodies have a built in means of controlling elastase, it makes sense to try and re-enable these means somehow.
Many of the exogenous inhibitors they test are the various flavonoids we often talk about all over this forum. These flavonoids are notorious for their lack of bioavailability. Many people including myself have tried several different methods of improving this by both topical and oral means to no real avail. The study here mentions this:
However, it has to be kept in mind that flavonoids are highly metabolized during oral application, and that some possible metabolites (such as 4-methylcatechol, 4-hydroxyphenylacetic acid and 3,4-dihydroxyphenylacetic acid ) exhibited a very low activity in the assay (IC50 range from 135 qM to > 400 juM, see Fig. 2A and Fig. 2B). Therefore, the in vitro studies mentioned above may be of limited therapeutic relevance and it is questionable that flavonoids may be orally active principles in a Drosera extract used to treat cough.
They say a very low IC50 value is achieved with EGCG (this means it is a strong inhibitor) but I've been taking that for a long time and it's actually in a lot of topical creams. It doesn't seem to do much in terms of restoring elastase in my opinion. If reversing the loss of elastase is the goal, then this is not exactly the outcome I'm seeing with EGCG.
So looking at exogenous possibilities...
Funny thing, they say stearic acid in this study was a fatty acid with the highest level of inhibition among saturated fats. Stearic acid has lengthy discussions in terms of fusion and stem cell proliferation in Turnbuckle's threads in this forum.
Erucic acid, which I've looked into as a problem with consuming ground broccoli seeds for the sulforaphane content, had the most potent inhibitory effect of all. An IC50 value of 450nM. The smallest amount will inhibit HNE by more than 50%. But what of the dangers of erucic acid? That's where oleic acid was mentioned which is also an omega 9 monounsaturated fatty acid capable of inhibiting HNE considerably, especially when they combined it with albumin.
Based on these results a formulation of oleic acid with albumin was developed for the treatment of chronic wounds. Albumin was used as a carrier for the hydrophobic oleic acid. Oleic acid/albumin formulations with mole ratios of 100:1, 50:1, and 25:1 showed a strong inhibition of HNE with IC50 values at 0.029-0.049 /iM. Albumin alone increased to a small extent the substrate conversion by HNE, which could be equalized by a higher concentration of inhibitor. The authors suppose that an increase of the albumin concentration may even have positive effects, since albumin level is decreased in chronic wounds. The formulation was still active (IC50 = 0.26-0.42 /iM), even after being bound to derivatized cotton.
So while albumin increased the substrate for HNE alone, more oleic canceled this out I assume. Not only that but the albumin might help heal wounds.
Mango butter is something I have on hand for the whole stem cell protocol. This is part largely stearic and oleic acid. I don't know about adding albumin but I may already have what I need, especially when I (hopefully) increase its bioavailability by adding phospholipids like soy lecithin and cocoa to the mix.
Resveratrol is also tested but of course, like all the flavonols, these are hardly bioavailable enough to work well in vivo. We've probably all been down this road.
So their conclusion in the study was that more study is needed of course. As I mentioned, addressing the root cause may be a more productive path, but there was not a complete description of how the endogenous inhibitors are thwarted from acting and moreover, how does the root cause affect any attempt to introduce exogenous inhibitors in vivo?
Edited by Nate-2004, 15 December 2018 - 06:06 PM.
