GHK and GHK-Cu may function as the circulating human non-steroidal anti-inflammatories (NSAIDs). In human plasma there is about 200 nanograms per milliliters of GHK and GHK-Cu at age 20. This declines to about 80 nanograms per milliliter at age 60 but these levels are highly variable. Given the respective binding constants for copper(+2) between GHK and albumin in human plasma, it is likely that only about 10% of circulating GHK is chelated with copper(+2). In areas of tissue damage, this ratio could be higher because of lowered albumin concentrations. There are very close similarities between the three dimensional chemical structures of GHK-Cu and H2-Receptor antagonists used as anti-ulcer medicines such as cimetidine, ranitidine, famotidine and nizatidine. Since GHK-Cu is a normal component of saliva present at about 40 nanograms/milliliter, it may function a natural protector of gastrointestinal linings. Also, most common anti-ulcer drugs are potent binders of ionic copper (II).There are also similarities, though less obvious, between most Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and GHK. Virtually all NSAIDs avidly bind copper(+2).

Similarities between GHK and Anti-Ulcers Pharmaceutics

Note the 3 main components -
(1) an N-terminal side change,
(2) and central imidazole ring,
(3)a C-terminal - lysine-like - very basic group

Intestinal and Stomach Healing

GHK-Cu has potent effects on the healing of stomach ulcers and intestinal inflammations. One small human study found a very positive effect of GHK-Cu on the healing of intestinal lesions in persons with refractory inflammatory bowel disease.

Effects of GHK-Cu on gastric acidity,
mucous production and the development of ulcers
(Shay gastric ulcer model (95% ethanol) in rats)

Dosage of GHK-Cu	Stomach pH	Rats with Visible Gastric	Gastric Mucous Production
None	2.3	72%	Unobservable
1 milligram	3.8	33%	++
3 milligrams	4.7	None	++++
10 milligrams	6.7	None	++++

Likewise, GHK-Cu produced a similar blockage of rat duodenal ulcer formation (cystamine induced).

Healing of Intestinal and Stomach Ulcers

Study - Healing of Stomach and Intestinal Ulcers

Result

GHK-Cu was tested for healing of experimental stomach ulcers and intestinal damage in rats.

GHK-Cu healed experimental stomach ulcers and intestinal inflammation and damage.

References

Study - Human Inflammatory Bowel Disease

Result

16 patients with refractory inflammatory bowel disease were treated with rectally administered solutions of GHK-Cu.

After the 12 weeks treatment, there was a 60% reduction in severity bas measured by endoscopy, histopathology, and symptoms.

References

Anti-Inflammatory Actions: Damaged Tissue

The anti-oxidant actions of GHK and GHK-Cu that help to protect injured tissue appear to have multiple actions. These are (1) a direct anti-inflammatory of the copper-peptide complex, (2) an activity that blocks the release of free iron from ferritin molecules, (3) an ability to block tissue damage caused by interleukin-1 at a GHK-Cu concentration of about 10exp(-10) M, and (4) an ability to block the oxidation of low density lipoproteins (LDL) by free copper.

Anti-Oxidant Actions

Study - Development of Tissue Protective Analogs of GHK-Cu

Result

GHK-Cu and analogs were tested for anti-oxidant and tissue protective properties GHK-Cu and analogs were found to enhance or restore resistance to oxidative or inflammatory damage. Certain analogs were 100-fold more effective than GHK-Cu.

References

Study - Blocking of Iron Oxidation

Result

A study of whether some of the wound healing properties of GHK-Cu are due to an affect on iron metabolism. The presence of iron complexes in damaged tissues is detrimental to wound healing, due to local inflammation, as well as microbial infection mediated by iron. The effects of GHK:Cu(II) on iron catalyzed lipid peroxidation. GHK:Cu(II) inhibited lipid peroxidation if the iron source was ferritin. Whereas GHK:Cu(II) inhibited ferritin iron release it did not exhibit significant superoxide dismutase-like or ceruloplasmin activity. It appears that GHK-Cu binds to the channels of ferritin involved in iron release and physically prevents the release of fee). Thus, a biological effect of GHK:Cu(II), related to wound healing, may be the inhibition of ferritin iron release in damaged tissues, preventing inflammation and microbial infections.

References

Study - Finding of Superoxide Dismutase and Catalase-like Activities in GHK Nickel Complexes

Result

The reactions between nickel ions and GHK and similar oligopeptides were characterized by spin trapping experiments.

GHK-Cu possessed superoxide dismutase and catalase-like activities.

References

Study - Anti-oxidant protection of insulin secreting cells after injury. Interleukin beta (IL-1 beta) is released during injuries and after tissue damage. IL-1 inhibits insulin release by pancreatic cells

Result

Jean-Honore Fragonard - The Fountain of Love

The study tested whether GHK-Cu would block the IL-1 damage to insulin secreting pancreatic cells. Rat pancreatic islet cells were incubated with or without 50 U/ml IL-1 beta, in the presence or absence of various concentrations of Cu(II)-GHK or CuSO4 (1-1000 ng/ml). After incubation, insulin secretion was evaluated in the presence of either 2.8 mmol/l (basal insulin secretion) or 16.7 mmol/l glucose (glucose-induced release). In control islets, basal insulin secretion was 92 +/- 11 ( pg/islet) and glucose-induced release was 2824 +/- 249. In islets pre-exposed to 50 U/ml IL-1 beta, basal insulin release was not significantly affected but glucose- induced insulin release was greatly reduced (841 +/- 76 ). In islets incubated with IL-1 beta and Cu-GHK (0.4 mumol/l, maximal effect) basal secretion was 119.0 +/- 13 and glucose-induced release was 2797 +/- 242. CuSO4 was without protective actions.

References

Study - Effect of GHK on Blocking Oxidative Damage that Produces Alzheimer's Disease

Result

Loosely bound copper(II) can produce oxidation of amyloid protein of Alzheimer's disease and cause neurodegeneration Loosely bound copper(II) can produce oxidation of amyloid protein of Alzheimer's disease and cause neurodegeneration.

References

Lord Frederick Leighton - The Reconciliation of the Montagues and the Capulets

Study - Increase Superoxide Dismutase in Wounds

Result

Biotin was attached to GHK then bound to collagen films. This gave increased wound contraction, increased cell proliferation, and produced a high expression of the antioxidant superoxide dismutase. Tissue copper levels were increased 9-fold.

References

Anti-Inflammatory Actions: General

Study - Blocking the oxidation of low density lipoproteins GHK tested on effecting the extent of in vitro Cu(2+)-dependent oxidation of low density lipoproteins (LDL)

Result

GHK blocked the extent of in vitro Cu(2+)-dependent oxidation of low density lipoproteins (LDL). Treatment of LDL with 5 microM of copper (+2) for 18 h in either phosphate buffered saline (PBS) or Ham's F-10 medium resulted in extensive oxidation as determined by the content of thiobarbituric acid reactive substances (TABORS). In PBS, oxidation was entirely blocked by gly-his-lys (GHK). In comparison , superoxide dismutase (SOD) provided only 20% protection.

References

Study - Angiotensin II appears to incite inflammatory processes that accelerated atheroma development. GHK interacts with the angiotensin II AT1 receptor.

Result

The effect of GHK on phosphorylase A was determined. Binding competition experiments using the radioligand [125I][Sar1-Ile8] angiotensin II measured the interaction of GHK with AT1 receptors.
GHK stimulated in dose-dependent fashion the activity of phosphorylase A in isolated rat hepatocytes. This effect was associated with increases in both IP3 production and [Ca++]. These effects of GHK were antagonized by losartan, a nonpeptide angiotensin II receptor antagonist (AT1 selective), which suggested that these receptors were involved in its effect. Binding competition experiments clearly indicated that GHK interacts with AT1 receptors.

References

Raphael - St Cecilia with Sts Paul John Evangelists Augustine and Mary Magdalene

Study - GHK-Cu Inhibits Platelet Aggregation

Result

GHK-Cu inhibits platelet aggregation at 10exp (-7) M

References

Study - GHK-Cu Inhibits Thromboxane Production

Result

Significant inhibition at 10exp (-7) M

References