Peptide therapy encompasses numerous different drugs with varied effects, ranging from immune modulation and tissue repair to fat loss and muscle building. Our center has seen very positive results in patients with CFS, Hashimoto’s thyroiditis, Lyme disease, and fibromyalgia, among other conditions. Ask your physician or speak to a patient representative at (877) 508-1177 to find out if peptide therapy is right for you.
The delegates have decided to accept the advice of the expert advisory committees that the current scheduling of preparations in Schedules 5 and 6 remains appropriate. The delegates noted the decision to retain listing of teeth whitening preparations containing up to 6 per cent hydrogen peroxide or 18 per cent carbamide peroxide in Schedule 5, or exempt when below 3 per cent and 9 per cent respectively, is to some extent also consistent with the evaluation of such products by the European Commission Scientific Committee on Cosmetics and Non Food Products intended for Consumers (SCCNFP).
TGA evaluator concluded that the consistent absence of any clinically meaningful effects on blood pressure (BP) or heart rate (HR) in the applicant's bioavailability studies, and the absence of any ADR reports of BP, HR or other cardiovascular problems, indicate that "there is no valid reason for concern and no need to take any regulatory against the combination products currently in the ARTG and available in the Australian market", i.e. no demonstrated safety risk, and no evidence provided of efficacy of paracetamol 1000 mg / phenylephrine HCl 5 mg adult dose.
Now you can use advanced D.N.A. enhancement which is beyond anabolic steroids! Learn about the one or two course of peptides anyone can get and make a change in the make up of your genetic blueprint for life. Unlike chemical enhancements, which require regular injections or oral administration to have a continued effect. Peptides specific to the system you are trying to enhance are availible now. Without any side effects unlike anabolic steroids.
GHRP-6 can effectively provide substantial increases in GH production. It’s typically taken 2-3 times per day by injection at times when blood sugar is not elevated. Cost is generally moderate. The only common potential adverse side effect is increased hunger. Common alternates include GHRP-2, hexarelin, ipamorelin, or GH itself. GHRP-6 also may provide benefits which GH does not, via its action at the ghrelin receptor in various tissues of the body.
Another very positive benefit of CJC1295 is its ability to promote slow wave sleep. Slow wave sleep (SWS) is also known as deep sleep and is the portion of sleep responsible for the highest level of muscle growth and memory retention. SWS is decreased significantly in older adults and also with people who tend to exercise later in the evening.  This peptide has a benefit to side effect ratio that exceeds all others currently being legally sold and would make a great addition to ones training regimen or post cycle therapy.
For increasing GH levels, GHRP-6 is less effective in the presence of high blood glucose levels or high somatostatin levels, which result from high IGF-1 levels. For this reason, for best effect GHRP-6 should be taken while blood sugar is relatively low, for example about 30-60 minutes before a meal. GHRP-6 will have reduced effect if GH is being taken by injection, because GH increases IGF-1. Where GH use is limited to no more than about 14 IU per week, simultaneous GHRP-6 use probably still will increase GH somewhat further, but if GH use is greater than this then likely GHRP-6 injections will do little to nothing towards increasing GH levels any further.
GH-releasing peptides (GHRPs) are synthetic peptides that like GHRH act directly on pituitary somatotrophs to stimulate GH release. Growth hormone (GH) release is stimulated by a variety of synthetic secretagogues, of which growth hormone-releasing hexapeptide (GHRP-6) has been most thoroughly studied; it is thought to have actions at both pituitary and hypothalamic site.
ADV Research ADV-11 (YK-11 SARM Alternative) All orders will be dispatched on Friday June 15th. KEY BENEFITS Powerful experimental myostatin inhibitor Potentially promotes lean muscle growth and increase lean body mass Potentially helps build on your genetic potential Potentially stimulates hair regrowth Potentially no negative impact on prostate size GENDER SUITABILITY ADV-11 may be suitable for use by both males…
In addition, scientists have observed that those who supplemented with IGF-1 experienced a preponderance of new brain cell growth and new muscle mass and new studies confirmed this to be true, even among individuals with both brain damage and muscle-wasting sarcopenia. Furthermore, research studies have found IGF-1 to increase feelings of youthfulness, improve well-being, and even to alleviate depression.
Experimental studies in 1997 proved that hexarelin could reverse the cardiac dysfunction in GH-deficient animals immunized by the administration of an anti-GHRH serum. Ex vivo and in vivo systems converged to document that hexarelin progressively and globally improved LV function even under postischemic scenarios. These experiments showed that the synthetic secretagogue protective activity was independent from any further stimulation derived from the somatotropic function.26 In 1998, this group demonstrated that hexarelin protected against postischemic ventricular dysfunction in senescent hearts of aged male rats. Both ex vivo and in vivo, GHRPs offered a striking heart protection against reperfusion stunning, improved ventricular pressures and volumes, and reduced CK concentration in perfusate. Again, they sustained the concept that the protection afforded by the peptide is likely due to a direct cardiotropic action that appeared far greater than that induced by GH administration in a concurrent control group.27 A more defining protocol was assumed in 1999 as the study included hypophysectomized rats, to ascertain whether hexarelin had non-GH-mediated protective effects on the heart. The authors showed that hexarelin attenuated the ischemia/reperfusion damage and prevented elevation of LV end-diastolic pressure, coronary perfusion pressure, reactivity of the coronary vasculature to angiotensin II, and the release of creatine kinase in hypophysectomized animals.28 These three experiments were pivotal to define GHRP intrinsic cardioprotective ability.
CJC-1295 10mg (Up to 10 Weeks): Started Wednesday 21 st September 2016 weight 122 kilo. Belly measurement 122cm Thursday 22nd September Weight @ 3pm 118.5 kilo Belly Measurement 117cm Morning and night 3 pumps Stacking with CJC1295 injectable. Lots of energy feel great aches and pains starting to subside.I will be doing a few more courses in the near future. THANKS Peptideclinics.com.au Awesome products. Shane Ridley
Triamcinolone acetonide (TA) has long been the steroid of choice for the treatment of skin fibrotic disorders, providing the best relief of local symptoms such as scars flattening. Nevertheless, TA is associated with adverse events such as dermal atrophy, telangiectasia, and immunosuppression [4, 5]. Despite the multitude of therapeutic strategies to prevent or reduce keloid and HTS formation, these conditions remain as orphan clinical niches of ultimately effective interventions [6].
Obviously, Increasing GH (and therefore IGF-1) levels are desirable for those looking to improve their physique in terms of increased muscle mass and loss of body fat, rejuvenation and strengthening of joints through connective tissue synthesis and bone mass density increases, as well as enhancing immune response and stimulating the immune system, particularly in those of us getting on in years (ahem). For anti-ageing purposes, GHRP-6 is normally singly dosed just before bed at night with users reporting the best night’s sleep they have ever had plus some funky dreams to match (since GH is released during REM or ‘dream sleep’ so the GHRP-6 sort of ‘forces’ us to dream). For bodybuilding purposes, users attempt to mimic pulsatile GH release for best results by administering multiple times throughout the day.

H.-M. Zhou, J. Wang, C. Elliott, W. Wen, D. W. Hamilton, and S. J. Conway, “Spatiotemporal expression of periostin during skin development and incisional wound healing: lessons for human fibrotic scar formation,” Journal of Cell Communication and Signaling, vol. 4, no. 2, pp. 99–107, 2010. View at Publisher · View at Google Scholar · View at Scopus


Then there’s colostrum. Colostrum is packed with growth factors, including IGF-1, that amplify lean muscle gains and increase the body’s ability to burn fat. In many studies, colostrum has been shown to restore IGF-1 and stimulate IGF-1 production. Colostrum is also a natural immunity drug, containing antibodies and antigens that knock out disease-causing agents such as bacteria, viruses, and fungi.
[2] Blocked growth hormone-releasing peptide (GHRP-6)-induced GH secretion and absence of the synergic action of GHRP-6 plus GH-releasing hormone in patients with hypothalamopituitary disconnection: evidence that GHRP-6 main action is exerted at the hypothalamic level. V Popovic, S Damjanovic, D Micic, M Djurovic, C Dieguez, and F F Casanueva. JCEM 1995 80: 942-7; doi:10.1210/jc.80.3.942.
Evidence review and acceptance by the NDPSC in 2007, demonstrated that paracetamol/caffeine combination analgesics have a very low risk of nephrotoxicity. Similarly, the combination analgesics pose a very low risk of toxicity in overdosing with only two fatal cases reported in the USA. However, these cases involved other medications in addition to paracetamol/caffeine with the latter being available in very large pack sizes. Further, there are no known contraindications to the paracetamol/caffeine combination apart from hypersensitivity to the constituents."
Despite their potent and reproducible GH-releasing activity, the clinical use of GHRPs as orally active growth-promoting agents and anabolic antiaging drugs remains to be confirmed.13 Accordingly, the early years’ enthusiasm as an alternative for GH replacement therapy faded away soon after their discovery.16 Nevertheless, it is likely that the myocardial, vascular, and multiorgan expression of the GHRP receptors may have contributed to reinforce the cardiovascular application stream of these peptides.

This is a great option for those who are looking to promote a steady and improved release of GH to get the benefits of increases in growth hormone and subsequently Insulin Like Growth Factor -1 (IGF-1) with almost no side effects. This therapy is effectively used for anti-aging purposes as well as those with inflammatory conditions, disease or those who have low IGF-1 levels.
Administration of peptides is normally subcutaneous or intramuscular. Peptides come as a fine white and delicate powder that must be reconstituted with bacteriostatic water or medical grade saline. An insulin syringe should always be used to administer the dose. When targeting muscles, look for a place where the layer of skin and fat are lean. Mixing two peptides in the same syringe is totally fine but I personally would advise not drawing/mixing doses and storing pins for future use.
Results: After a single injection of CJC 1295, there were dose dependent increases in mean plasma GH concentrations by 2- to 10-fold for 6 d or more and in mean plasma IGF-I concentrations by 1.5- to 3-fold for 9–11 d. The estimated half-life of CJC 1295 was 5.8–8.1 d. After multiple CJC 1295 doses, mean IGF-I levels remained above baseline for up to 28 d. No serious adverse reactions were reported.
Growth Hormone Releasing Peptide 6 ( GHRP-6) is a peptide which substantially activates the pituitary gland into releasing high levels of growth hormone for a few hours. The increase in growth hormone comes from your own body, not synthetic growth hormones which can suppress your natural production. GHRP 6 is a first generation GHRP and has a few side effects which could be annoying.
200 to 300 mcg is typically the daily dosage which is recommended for the typical Ipamorelin user. It can be taken anytime during the day but is advisable to be used in the morning, as it will help you achieve the best results in such cases. Regardless of when you start your dosage, it is important to ensure you are taking it at the same time each day. And, for new users, it is best to stick to a one-a-day cycle.
IGF-1 also increases the activity of muscle protein synthesis and the activity of muscle stem cells (also called satellite cells) for repair of damaged muscle. This is probably why intense weight training is one primary stimulus for a natural release of IGF-1 in muscle. As a matter of fact, exercise researchers have found that systemic IGF-1 normally produced in the liver isn’t even required for this type of muscle repair, as other IGF-1 forms produced by your own muscles during and post-exercise allows for adequate muscle tissue repair.
If you are interested in order a product you will need to fill out our quick 2-minute Medical Questionnaire. As we provide Schedule 4 medication we require your medical details so our Prescribing Doctor can provide you with the safest and most effective solution for your health and fitness goals. If you have any further questions surrounding our Order Process please feel free to call out Customer Support team to discuss any concerns.

The sports pros and scientists have known about significance of peptides for bodybuilding and performance enhancement for many years but it is just in the last 2-3 years that the researchers have been able to know the dipeptides and tripeptides in the hydrolysed whey proteins that offer positive results on sports recovery and bodybuilding performance. So, if you really wish like achieving the desired bodybuilding goals, you can take natural peptide supplements.
Increasing HGH release levels in your body naturally. It sounds too good to be true, but what if you could achieve just that by using a supplement? Using Ipamorelin alongside your exercise and diet regimen is going to help you achieve said goal. No two users are alike. For athletes or those who workout religiously, you might experience greater results than an individual who is overweight and just getting back into the gym after 10 years. So, take it with a grain of salt when detailing the results below. Dosage, your body composition, and other factors will play a role in the results you can expect to see when you incorporate Ipamorelin.
In October 2005, the NDPSC decided to amend the Schedule 5 entry for thyme oil to include the wording "in medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels".
Mod GRF 1-29 and CJC-1295 are still being researched. As such, they are not yet medically utilized or approved. Though some firm protocols for the use of these peptides have been developed, the dosage of the compound is not yet medically confirmed. In a study conducted by researchers on 21 to 61 year-old subjects, it was found that depending on the dose, the concentrations of the growth hormone increased to up to 10 times for at least 6 days. Also, the concentration of IGF-1 increased to up to 3 times for 9 to 11 days.
Investigations reported that GHRP-6 is more efficient than GHRH itself in monkeys and performs synergistically when combined or applied together. An example of this combination would be GHRP-2 and CJC-1295. GHRP-6 is believed to be acting naturally on both pituitary and hypothalamic sites (Fairhall et al. 1995). In a time-dependent and dose-dependent manner, the primary pituitary cells of rats were demonstrated on. From the studies, the concentrations of the GHRP-6 needed for the half-maximal and maximal stimulation were 7 x 10(-9) and 10(-7) M, respectively.
IGF-1 is the only natural hormone that can stimulate lean muscle mass gains and help the body choose to burn stored fat over simple glucose for fuel, meaning, you will burn off more fat. Studies demonstrate that only colostrum supplements containing lactoferrin can produce lean muscle gains that complement IGF-1 supplementation. That’s because it is actually the lactoferrin in some brands of colostrum that work to increase muscle mass and to burn adipose tissue. In fact, in a recent 2013 study, participants who supplemented with lactoferrin over a period of eight weeks experienced increased weight loss, reduced visceral and subcutaneous fat, reduced waist circumference, and reduced hip circumference.
Years ago, our group examined the cytoprotective effects exerted by the GHRP-6 preventive administration in the hepatic tissue subjected to I/R, as in other distal organs from the ischemic site (ie, lungs, kidneys, and small intestine). Histological and biochemical results allowed us to conclude that the pharmacological preconditioning induced by the GHRP-6 treatment attenuated I/R liver damage. Besides respiratory distress syndrome like pulmonary changes, intestinal transmural infarct and acute tubular necrosis in kidneys were significantly reduced. These results indicated for the first time a systemic cytoprotective effect for the GHRP-6, suggesting its potential efficacy to control the inflammatory response associated with acute I/R and shock, which eventually originated multiple organs damage (MOD). Cytoprotection induced by GHRP-6 treatment was also related to the attenuation in the generation of ROS and preservation of the antioxidant defense reserves. Histological analysis as the assessment of myeloperoxidase activity evidenced a clear anti-inflammatory GHRP-6-induced effect in the liver and remote organs. Moreover, the molecular mechanism mediating the action of GHRP-6 peptide was shown to involve the phosphatidylinositol 3-kinase/RAC-alpha serine/threonine-protein kinase (PI-3K/AKT1) pathway, as the induction of the hypoxia-inducible factor-1 alpha (HIF-1α) all committed in cellular survival.51 Subsequently, Granado et al52 examined the potential anti-inflammatory impact of GHRP-2 in lipopolysaccharide (LPS)-challenged rats. GHRP-2 administration attenuated the effects of LPS on the elevation of circulating levels of transaminases, nitrites/nitrates, and tumor necrosis factor-alpha (TNF-α), via direct interaction with liver nonparenchymal cells. Globally, the exogenous administration of these two synthetic GHRPs appeared to exert a potent hepatoprotective role by attenuating the inflammatory response orchestrated by liver-resident macrophages. Another line of evidences document the benefits of 15-daily injections of GHRP-2 (100 μg/kg) in arthritic rats, so that the treatment ameliorated the external symptoms of arthritis and decreased the circulating levels of interleukin 6 (IL-6) as the nitrite/nitrate release from peritoneal macrophages in vitro. This experiment extrapolated the counter-inflammatory properties of GHRP-2 to a nonepithelial organ and suggested again a direct interaction with ghrelin receptor of immune cells.53 Similarly, effects have been attributed to ghrelin by inhibiting the inflammatory response via AKT1-activated pathway with a concomitant reduction of myeloperoxidase activity, the rate of apoptosis, and oxidative stress.54 All these data suggest that GHRPs exert a mutually inclusive beneficial effect by directly protecting parenchymal organs epithelial cells, and simultaneously by modulating the magnitude of the inflammatory response by direct interaction with the effector immune cells. Supporting the protective effect of GHRP-6 on epithelial organs, a recent study has excellently described and dissected the mechanistic bases on how GHRP-6 prevented gastric mucosal damage induced by water immersion restraint (WRS) and other forms of stress. The data indicated that the protective effect of GHRP-6 on WRS-induced gastric mucosal injury is somehow mediated by peripherally suppressing the vagal efferent effect on the stomach, including gastric acid secretion. Although more studies are clearly demanded, the present findings open the possibility to use GHRP-6 in preventing Curling ulcers.55
The interim decision was to include in Schedule 4 and in Appendix D Item 5 Growth Hormone Releasing Hormones (GHRHs), Growth Hormone Secretagogues (GHSs), Growth Hormone Releasing Peptides (GHRPs) as well as new individual substance entries for CJC-1295, ipamorelin, pralmorelin (Growth Hormone Releasing Peptide-2), Growth Hormone Releasing Peptide-6, hexarelin and AOD-9604.

They appear to be safer than anabolic steroids too, but don’t think that means they’re unequivocally safe to take. Research clearly shows that they do suppress natural testosterone production and negatively impact the endocrine system, and there’s evidence to suggest that they may increase the risk of cancer to a far greater degree than any natural supplement ever will.

Ryan also brings up a good point to bring up the fact that GHRH receptors are typically not desensitized with higher dosing but again not much accomplished with CJC-1295, ,MOD GRF 1-29 where we know the 100mcg is a saturation dose. on the other hand we can desensitize the GHRP receptor if we start increasing the dosing significantly above the saturation dosing  of 100mcg. I think you are fine at a 150 mcg dosing but again how much more benefit are you really getting.
Finally, patients deficient in growth hormone who get IGF-1 injections have shown increased rates of fat loss and fat oxidation. One theory for this is that, as you’ve just learned, IGF-1 can suppress circulating insulin, which would allow more burning of fatty acids from fat cells. This makes sense, since we do know that fat cells contain IGF-1 receptors, and this means that IGF-1 can interact with fat cells.

Y.-T. Shen, J. J. Lynch, R. J. Hargreaves, and R. J. Gould, “A growth hormone secretagogue prevents-ischemic-induced mortality independently of the growth hormone pathway in dogs with chronic dilated cardiomyopathy,” Journal of Pharmacology and Experimental Therapeutics, vol. 306, no. 2, pp. 815–820, 2003. View at Publisher · View at Google Scholar · View at Scopus


The delegates have decided that the relevant matters under subsection 52E(1) of the Therapeutic Goods Act 1989 are (a) the risks and benefits (b) the purpose for and the extent of use (c) the toxicity (d) the dosage, formulation, labelling, packaging and presentation (e) the potential for abuse and (f) any other matters considers necessary to protect public health.
Exercise and sports have, in recent times gained the credit it is due. Not only are these sports a testament to the fortitude of the athletes, but they are also a science in themselves. Each sport has different exercise regimes and different dietary requirements. While some athletes face the same environment in each competition, there are those who have to face a different environment every time they compete. What remains constant however is the importance of growth hormone and the effect it has on the athlete’s body.
Before the discovery of ghrelin, synthetic GH secretagogs were available. Several studies investigated the effects of these substances on human sleep. Oral administration of the GH secretagog MK-677 for 1 week prompts a distinct sleep-promoting effect in healthy young male volunteers, whereas a weak effect is observed in elderly subjects. This study shows that oral administration of a peptide is capable of promoting sleep. After repetitive intravenous administration of GH-releasing peptide 6 (GHRP-6), non-REM sleep stage 2 increases. Similar to the effects of ghrelin in male subjects GH, ACTH, and cortisol are elevated. In a set of studies, the intranasal, oral, and sublingual administration of GHRP-6 was tested. By these routes of administration the effects of the peptide on the sleep EEG and on hormone secretion are less distinct and partly different from those after intravenous injection. In contrast to the sleep-promoting effects of GHRP-6 and ghrelin, hexarelin prompts a decrease of SWS, whereas the pattern of endocrine effects after hexarelin resemble the endocrine changes after ghrelin and GHRP-6 in that there is a marked stimulation of GH. The decrease of SWS after hexarelin may be related to negative feedback inhibition of endogenous GHRH. After a single dose of GHRP-2 during the third period of REM sleep, sleep remains unchanged. The lack of effects in this study may be related to the method that uses only a single injection of the substance.

The Work around is GHRH + GHRP. If GHRH help stimulate growth hormone and GHRP can stimulate twice as much, once you combine the two you are going to increase the amount of growth hormone that can be secreted by 12 times. GHRH will increase the amount of growth hormone that is secreted at the natural times when your body is ready to release the GH. GHRP will selectively send a pulse forcing GH to be secreted. Taking the two together, the GHRP will force a pulse and the GHRH will increase the power of that pulse. Basically, the power of that pulse will be greater, and with more frequency, when using GHRP and GHRH together. This combination gives the option for users to mix and match; thereby, finding which peptides work best for them.

GHRP-6 is most commonly provided in small vials of 5 mg, which should be stored under refrigeration. (It is acceptable however for them to be mailed unrefrigerated.) The vial is diluted with a convenient volume of sterile or bacteriostatic water. For example, the vial might be diluted with 2.5 mL of water, yielding a solution of 2 mg/mL (2000 mcg/mL.) After the water addition, the vial again will be stored under refrigeration.
IGF-1 causes hyperplasia and muscle and strength increase, looove IGF-1 (insulin-like growth factor). GHRP-6 causes your pituitary gland the secret growth hormones so you get a 'pulse' after each shot. The more shots, the more pulses you get which is why I split it up to 3 times a day. You feel amazing post-shot and also hungry as fuuu within 20 minutes, like a bottomless stomach. Also helps with fat-loss.
Figure 3.2 shows changes in intracellular calcium concentrations in several GHS-R-expressing cell lines as detected by fluorometric imaging plate reader (FLIPR)-based assays. Isolated GHS-R-expressing cell lines were activated by GHRP-6, an artificial ligand to GHS-R. The calcium changes varied in each cell line in relation to the expression levels of GHS-R mRNA.
It is important to understand that GHRP-6 doses on its own provides considerable HGH release from the pituitary gland, but is nowhere near as effective as the potential HGH release resultant from GHRP-6 combined with a GHRH such as Mod GRF 1-29 (CJC-1295 without DAC). Studies have demonstrated that the combination of GHRP-6 and a GHRH analogue such as Mod GRF 1-29 will generate a 77% increase in HGH output compared to GHRP-6 administration alone[8]. Other studies have gone so far as to explicitly state that GHRP-6 requires GHRH in order to stimulate maximal HGH stimulation as evidenced by the fact that in test subjects, the inclusion of a GHRH can increase HGH output by an additional 81 – 95%[9].
Peptide can be defined as the chain of 50 or lower amino acids with amino carboxyl end, though there are some exceptions to the rule. Bodybuilding peptides are actually closely related to the proteins, differing only by amount of amino acids that are present in the chain. Generally people think that proteins and peptides are the same and so they use them interchangeably. The confusion arises because insulin serves as both a protein as well as peptide. Peptides can basically be natural in their origin and found in regular daily diet.
ADV Research ADV-11 (YK-11 SARM Alternative) All orders will be dispatched on Friday June 15th. KEY BENEFITS Powerful experimental myostatin inhibitor Potentially promotes lean muscle growth and increase lean body mass Potentially helps build on your genetic potential Potentially stimulates hair regrowth Potentially no negative impact on prostate size GENDER SUITABILITY ADV-11 may be suitable for use by both males…
Technically, it is a “protein-peptide hormone” which means that it consists of 70 amino acids bonded together. Just like the peptides I’ve written about in the past, this means that it must be injected, because otherwise IGF-1 simply degrades in the gut, rendering it useless. Your own human growth hormone release promotes the synthesis of IGF-1 in your liver (and to smaller amounts, synthesis of IGF-1 by your muscles), your liver and muscles then synthesize IGF-1 and then, in the case of your liver, subsequently package the IGF-1 with binding proteins for transport into the blood. In a type of anabolic positive-feedback loop, IGF-1 then further increases growth hormone’s anabolic effects.
The ACMS recommended listing Growth Hormone Releasing Hormones (GHRHs), Growth Hormone Secretagogues (GHSs), Growth Hormone Releasing Peptides (GHRPs) as well as new individual substance entries for CJC-1295, ipamorelin, pralmorelin (Growth Hormone Releasing Peptide-2), Growth Hormone Releasing Peptide-6, hexarelin and AOD-9604 in Appendix D, Item 5.
Years ago, our group examined the cytoprotective effects exerted by the GHRP-6 preventive administration in the hepatic tissue subjected to I/R, as in other distal organs from the ischemic site (ie, lungs, kidneys, and small intestine). Histological and biochemical results allowed us to conclude that the pharmacological preconditioning induced by the GHRP-6 treatment attenuated I/R liver damage. Besides respiratory distress syndrome like pulmonary changes, intestinal transmural infarct and acute tubular necrosis in kidneys were significantly reduced. These results indicated for the first time a systemic cytoprotective effect for the GHRP-6, suggesting its potential efficacy to control the inflammatory response associated with acute I/R and shock, which eventually originated multiple organs damage (MOD). Cytoprotection induced by GHRP-6 treatment was also related to the attenuation in the generation of ROS and preservation of the antioxidant defense reserves. Histological analysis as the assessment of myeloperoxidase activity evidenced a clear anti-inflammatory GHRP-6-induced effect in the liver and remote organs. Moreover, the molecular mechanism mediating the action of GHRP-6 peptide was shown to involve the phosphatidylinositol 3-kinase/RAC-alpha serine/threonine-protein kinase (PI-3K/AKT1) pathway, as the induction of the hypoxia-inducible factor-1 alpha (HIF-1α) all committed in cellular survival.51 Subsequently, Granado et al52 examined the potential anti-inflammatory impact of GHRP-2 in lipopolysaccharide (LPS)-challenged rats. GHRP-2 administration attenuated the effects of LPS on the elevation of circulating levels of transaminases, nitrites/nitrates, and tumor necrosis factor-alpha (TNF-α), via direct interaction with liver nonparenchymal cells. Globally, the exogenous administration of these two synthetic GHRPs appeared to exert a potent hepatoprotective role by attenuating the inflammatory response orchestrated by liver-resident macrophages. Another line of evidences document the benefits of 15-daily injections of GHRP-2 (100 μg/kg) in arthritic rats, so that the treatment ameliorated the external symptoms of arthritis and decreased the circulating levels of interleukin 6 (IL-6) as the nitrite/nitrate release from peritoneal macrophages in vitro. This experiment extrapolated the counter-inflammatory properties of GHRP-2 to a nonepithelial organ and suggested again a direct interaction with ghrelin receptor of immune cells.53 Similarly, effects have been attributed to ghrelin by inhibiting the inflammatory response via AKT1-activated pathway with a concomitant reduction of myeloperoxidase activity, the rate of apoptosis, and oxidative stress.54 All these data suggest that GHRPs exert a mutually inclusive beneficial effect by directly protecting parenchymal organs epithelial cells, and simultaneously by modulating the magnitude of the inflammatory response by direct interaction with the effector immune cells. Supporting the protective effect of GHRP-6 on epithelial organs, a recent study has excellently described and dissected the mechanistic bases on how GHRP-6 prevented gastric mucosal damage induced by water immersion restraint (WRS) and other forms of stress. The data indicated that the protective effect of GHRP-6 on WRS-induced gastric mucosal injury is somehow mediated by peripherally suppressing the vagal efferent effect on the stomach, including gastric acid secretion. Although more studies are clearly demanded, the present findings open the possibility to use GHRP-6 in preventing Curling ulcers.55
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