Peptides

Table Of Peptides

Peptide are proteins found in the body that govern physiological processes.  At this time point, there are many peptides being used within this new frontier of medicine. Peptides  are an emerging modern medicine that will revolutionize safe and natural health and healing for your body. The medical-scientific community has been researching these physiological peptides for decades, as they are integral to human physiology. For instance the best known peptide within clinical practice is insulin. Peptides serve a broad range of benefits across the entirety of physiology. Peptides are plentiful in their functions, including the production of enzymes to help your body break down foreign substances,  enhance a broad immune function and hormones  controlling everything from growth, healing neuroprotective and enhancing ect. Without peptides, life would not be possible.

The following is a list of links to these powerful Healing medicines:

 

 

 


 

BPC-157

DESCRIPTION

Pentadecapeptide BPC 157, composed of 15 amino acids, is a partial sequence of
body protection compound (BPC) that is discovered in and isolated from human
gastric juice. Experimentally it has been demonstrated to accelerate the healing of
many different wounds, including tendon-to-bone healing and superior healing of
damaged ligaments.

In addition, BPC 157 seems to protect organs and to prevent ulcers of the stomach.
BPC-157 acts systemically in the digestive tract to combat leaky gut, IBS,
gastro-intestinal cramps, and Crohn’s disease.

This peptide is also shown to decrease pain in damaged areas. Those who suffer
from discomfort due to muscle sprains, tears and damage may benet from treatment
with this peptide. It can also help aid skin burns to heal at a faster rate and increase
blood ow to damaged tissues.

PROTOCOL

Content & Potency: 1x 5ml at a concentration of 2000mcg/ml : ready to inject
subcutaneously

Suggested dosage: 0.15ml (15 units) injected subcutaneously every day for 3 days
Oral option: 30 capsules at 500mcg – Take one capsule per day for 30 days total

CLINICAL RESEARCH

The Promoting effect of Pentadecapeptide BPC 157 on tendon healing involves
tendon outgrowth, cell survival, and cell migration Chung-Hsun Chang,
Wen-Chung Tsai2 Miao-Sui Lin, Ya-Hui Hsu, and Jong-Hwei Su Pang
Many growth factors such as epidermal growth factor (EGF), transforming growth
factor-(TGF-), and bone morphogenetic proteins (BMPs) have been used to
improve the healing of torn tendon in the lab (2, 31). However, the short duration of
these easily digested growth factors hampers their clinical usage. Gastric
pentadecapeptide BPC 157 is a partial sequence of human gastric protein BPC,
which has been discovered in and isolated from gastric juice (5). It is highly stable
and resistant to hydrolysis or enzyme digestion, even in the gastric juice. Besides,
it is easily dissolved in water and needs no carrier for its application. Experimentally
it was demonstrated to enhance the healing of different wounds, such asgastric
ulcer (19, 32), skin (4, 15), cornea (13), muscle (28), colon-colon anastomosis (22),
colocutaneous stula (11), and segmental bone defect (21). It was also found to
accelerate the healing of transected rat Achilles tendon (12, 29) and medial
collateral ligament of knee (8). Currently it is in clinical trial for treating inammatory
bowel disease.


Cerebyomysin

DESCRIPTION

Cerebrolysin (synonym FPE 1070) is a synthetic nootropic drug which consists of
low-molecular peptides and possesses neuroprotective and neurotrophic repair
properties. The active fragment of cerebrolysin is made of proteins with very low
molecular masses that do not exceed 10.000 daltons. This means they can penetrate
the blood-brain (or blood-SCF) barrier and reach neurons directly, making the drug
able to show organo-specific combined effects towards brain.

Cerebrolysin has been proven to have neurotrophic action similar to nerve growth
factors, which cause peripheral and central neuronal stimulation. It improves
efficiency within the brain’s aerobic metabolic processes and improves intracellular
peptide synthesis. The neuroprotective properties of this nootropic agent help to
shield neurons from lactocidosis, to prevent formation of free radicals and to
decrease.

PROTOCOL

Content & Potency: 215.2mg/mL x 10mL x 4 vials : ready-to-inject subcutaneously
Suggested dosage: Inject 1ml daily for 5 days out of 7 (4 week course)
Oral option: 40 capsules at 215mcg – Take one capsule per day for 40 days (Ask for
availability)

CLINICAL RESEARCH

Cerebrolysin in Alzheimer’s disease: a randomized, double-blind,
placebo-controlled trial with a neurotrophic agent

M. Panisset, S. Gauthier, H. Moessler, M. Windisch
Summary: Cerebrolysin (Cere) is a compound with neurotrophic activity. It has
been shown to be effective in the treatment of Alzheimer’s disease (AD) in earlier
trials. In this multicenter, randomized, double-blind, placebo-controlled,
parallel-group study, patients were injected intravenously with placebo or 30mL
Cere five days per week for four weeks. Effects on cognition and global function
were evaluated with the Alzheimer Disease Assessment Scale – Cognitive
Subscale (ADAS-Cog) and the Clinicians Interview based Impression of Change
with Caregiver Input scale (CIBIC+) 4, 12, 24 weeks after the beginning of the
injections. 192 patients were enrolled, 95 were randomized to placebo, and 97 to
Cere. At baseline, there was a significant difference between groups for age, age of
onset of dementia, and the number of patients with hallucinations. At week 12 there
was a significant difference on the CIBIC + (p=0.033) in favor of Cere. The number
of CIBIC+ responders (score < 4), was significantly higher (p=0.007), with 68 (76%)
in the Cere group and 51 (57%) in the placebo group. Trends were noted in the
Disability Assessment in Dementia scale and the Cornell Depression Scale.
Adverse events were recorded in 73% of placebo and 64% of Cere patients. Most
common adverse events were headaches, dizziness, weight loss and anxiety.
Conclusions: Cere treatment was well tolerated and resulted in significant
improvements in the global score two months after the end of active treatment.


CJC 1295

Growth Hormone Releasing

DESCRIPTION

CJC 1295 has been shown to increase growth hormone as well as IGF-I secretion
and it has been able to do so in very large amounts. CJC 1295 stimulates growth
hormone secretion and will keep a steady increase of HGH and IGF-1 with no
increase in prolactin, leading to fat loss, and increased protein synthesis thereby
promoting growth.

CJC 1295 is a tetrasubstituted 29-amino acid peptide hormone, primarily functioning
as a growth CJChormone1295 releasing is a tetra substituted hormon(GHRH)30-aminalogoacid. peptide hormone,
primarily functioning as a growth hormone releasing hormone (GHRH) analog. with
time and the body produces anti-bodies to Sermorelin. bioconjugate with serum
albumin, thus increasing its half-life and potential therapeutic window. It
accomplishes this by using protecting groups around the amino acids of GHRH
typically susceptibledesigndo toprenzymaticvmdegradationiction. thus increasing the
half-life. Consequently CJC 1295-DAC is designed to provide a GHRH-like
stimulation around the clock. A potential drawback when using a Various
experiments have been conducted to test the pharmacokinetics of CJC 1295-DAC in
vivo and the Journal of Clinical Endocrinology & Metabolism has reported
dose-dependent increases in mean plasma GH concentrations by 2-10 fold for more
than 6 days and increased IGF-1 concentrations 1.5-3 fold for 9-11 days a er a single
injection. Mean half-life was shown to be 5.8-8.1 days,also a er multiple doses mean
IGF-1 levels remained above baseline for up to 28 days. No serious adverse
reactions were reported in any group.

PROTOCOL

Content & Potency: 1 x 2ml at 2000mcg/ml : ready-to- inject subcutaneously

Suggested dosage: 0.10ml per day 5 days out of 7 (NON-DAC) before bed, on an
empty stomach (1 month supply). Some will do multiday dosing of 0.05ml.
***We suggest using the CJC 1295 in combination with Ipamorelin as it provides a
synergistic e ect, generating ve times the bene ts of using the CJC 1295 or
Ipamorelin alone. e combination allows for maximized release of GH because the
CJC 1295 and Ipamorelin have di erent mechanisms of action and work on di erent
receptors (GHRH-R & Ghrelin-R).


DSIP

Nueropeptide

DESCRIPTION

DSIP is a well-known neuromodulator and natural somnogenic nonapeptide with
many other physiologic functions. It is typically found in the brain and easily passes
the blood-brain barrier. It is mainly prescribed for the treatment of pain condition,
alcohol and opioid withdrawal, CRH and stress related symptoms, low testosterone
(via stimulation of LH), and even sometimes as an antioxidant and anti-oncogenic
protein.

It has been discovered and heavily studied for over 40 years, yet, the mechanism of
action is still complex and not well organized. The results of studies of DSIP and its
analogues over a period of 30 years since its discovery enable one to state with
confidence that DSIP is a unique member of the family of peptide neuromodulators. It
exhibits a pronounced stress protective action and decreases stress-induced
metabolic and functional disorders in human and animal organisms exposed to a
variety of stresses. Some of the effects of the peptide are accomplished through the
modulating action on central regulatory processes, owing to the systemic antioxidant
action, the modulating influence on the activity of GABAergic, glutamatergic, and
other neuronal systems. It also works on the expression of early response genes in
brain structures, and on the activity of biosynthetic and proteolytic processes.

PROTOCOL

Content & Potency: 1 x 3ml at 1000mcg/ml: ready-to-inject subcutaneously
Suggested dosage: DSIP has traditionally been dosed as an IV infusion, however, it can
be given subcutaneously as well. Traditional doses have been 100mcg.
Often prescribed for: Pain, to help improve sleep, and to stimulate testosterone levels
via LH release.

CLINICAL RESEARCH

In several species DSIP at low doses has been shown to promote sleep. Although its
physiological role remains to be clarified, DSIP illustrates several concepts applicable to
other brain peptides. These include the bell-shaped dose-response curve, central effects
after peripheral administration, a delayed and prolonged time course, and some
penetration of the blood-brain barrier in essentially intact form. Concepts applicable to
one neuropeptide, therefore, appear to be applicable to others. In this article Abba Kastin
and colleagues review the known effects of DSIP and argue that more work needs to be
carried out before it can be labelled functionally.


Thymosin

Alpha-1

DESCRIPTION

Thymosin α-1 is a major component of Thymosin Fraction 5 and is responsible for
restoring immune function, particularly cell mediated immune function. Recent
studies showed that the Thymosin Alpha-1 molecule increased major
histocompatibility complex (MHC) class-1 and Toll-like receptor expression as well as
cytokine production, suggesting its immunoregulatory role.

The drug is in Phase III trials for the treatment of hepatitis C and in Phase II trials for
hepatitis B. Additional possible indications are malignant melanoma, hepatocellular
carcinoma, drug-resistant tuberculosis, and Di George’s syndrome as well as any
chronic cancer or viral disease. Some physicians are using thymosin for chronic
fatigue and Lyme disease as well.

TA 1 is thought to modulate the immune system by augmenting T-cell function. TA1
may affect thymocytes by stimulating their differentiation or by converting them to
active T cells. TA1 is rapidly absorbed, achieving peak serum concentrations within
two hours. Blood levels return to baseline within 24 hours, and the serum half-life is
approximately 2 hours.

PROTOCOL

Content & Potency: 1 x 5mL at 3000 mcg/mL ready-to-inject subcutaneous.
Suggested dosage: Inject .15mL subcutaneously once daily until vial is empty (1 month
supply) or inject 1.6mg 2 x 1 week.

CLINICAL RESEARCH

Thymosin Alpha 1: Past clinical experience and future promise
Cynthia Tuthill, 1 Israel Rios, 2 and Randy McBeath3
1Scientific Affairs, SciClone Pharmaceuticals, Inc., Foster City, California, USA.
2Medical Affairs, SciClone Pharmaceuticals, Inc., Foster City, California, USA.
3Marketing, SciClone Pharmaceuticals, Inc., Foster City, California, USA Address
for correspondence: Cynthia Tuthill, Scientific Affairs, SciClone Pharamaceuticals,
Inc., 950 Tower Lane, Foster City, CA 94404, USA. ctuthill@sciclone.com
Abstract: Thymosin alpha 1, originally isolated as the compound responsible for
reconstitution of immune function in thymectomized animal models, has enjoyed a
wide-ranging clinical development program over the past decades, extending across
multiple companies, indications, countries, and continents. This paper provides an
overview of this complex picture. The extensive clinical studies began with small
studies conducted with an impure mixture of peptides under the awgis of
physician-sponsored INDs submitted to the US FDA, in subjects with primary
immune deficiency such as DiGeorge syndrome. Subsequent studies ranged all the
way to large phase-3 trials conducted with synthetically produced thymosin alpha 1
and hundreds of patients, in many countries including the Untied States, Italy, and
China.
Thymosin Alpha 1: Biological activities, applications and engineering
production

Juan Li a, Chun Hui Liu a, Feng Shan Wanga

A Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical
Sciences, Shandong University, Jinan 250012, China b National Glycoengineering
Research Center, Shandong University, Jinan 250012, China
Abstract: Thymosin alpha 1 (T1), a 28-amino acid peptide, was first described and
characterized from calf thymuses in 1977. This peptide can enhance T-cell, dendritic
cell (DC) and antibody responses, modulate cytokines and chemokines production
and block steroid-induced apoptosis of thymo-cytes. Due to its pleiotropic biological
activities, T1 has gained increasing interest in recent years and has been used for
the treatment of various diseases in clinic. Accordingly, there is an increasing need
for the production of this peptide. So far, T1 used in clinic is synthe-sized using solid
phase peptide synthesis. Here, we summarize the genetic engineering methods to
produce T1 using prokaryotic or eukaryotic expression systems. The effectiveness of
these biological products in increasing the secretion of cytokines and in promoting


Thymosin

Beta-4

DESCRIPTION

Thymosin is a hormone secreted from the thymus. Its primary function is to stimulate
the production of T cells, which are an important part of the immune system.
Thymosin also assists in the development of B cells to plasma cells to produce
antibodies. The predominant form of Thymosin. Thymosin Beta 4, is a member of a
highly conserved family of actin monomer-sequestering proteins. In addition to its
role as a major actin-sequestering molecule, Thymosin Beta 4 has a role in tissue
repair. Tβ4 has been found to play an important play an important role in protection,
regeneration and remodeling of injured or damaged tissues. The gene for Tβ4 has
also been found to be one of the first to be unregulated after injuries. Thymosin Beta
4 is currently being trialed as a potential therapy for HIV, AIDS, and Influenza.
Thymosin Beta 4 is most often prescribed for acute injury, surgical repair and for old
athletes. It has most recently been shown to help regrow hair in addition to PRP.

PROTOCOL

Content & Potency: 1 x 5ml at 3000mcg/ml ready-to-inject
Suggested dosage: Inject 0.25ml daily for 20 days

CLINICAL RESEARCH

Abstract: A cDNA clone encoding human thymosin-beta 4 was isolated from a
cDNA library prepared from peripheral blood leukocytes of a patient with acute
lymphocytic leukemia. This clone contained the entire coding sequence of 43
amino acid residues of thymosin-beta 4 and had an initiation codon and two
termination codons. The amino acid and nucleotide sequences in the coding region
were well conserved between rat and human. Nine of 132 nucleotides were
different in the coding sequences (93% homology), but the deduced amino acid
sequences were identical. No signal peptide was found in the deduced protein
sequence. Human thymosin-beta 4 mRNA, approximately 830 nucleotides in
length, was about 30 nucleotides larger than rat thymosin-beta 4 mRNA.
Expression of the human thymosin-beta 4 gene in various primary myeloid and
lymphoid malignant cells and in a few human hemopoietic cell lines was studied.
Northern blot analyses of different neoplastic B lymphocytes revealed that steady
state levels of thymosin-beta 4 mRNA varid as a function of differentiation stage.
Thymosin-beta 4 mRNA levels were decreased in myeloma cells as are class II
human leukocyte antigen, Fc receptor, and complement receptor, suggesting a
relationship between thymosin-beta 4 and the immune response. Thymosin-beta 4
mRNA was more highly expressed in mature granulocytes than in immature blastic
cells. Treatment of THP-1 cells, a human monocytic cell line, with recombinant
human interferon-lambda reduced the levels of thymosin-beta 4 mRNA. Its level
decreased after differentiation of THP-1 cells into Ia+ macrophages, but increased
after differentiation of HL-60 cells into Ia- macrophages. The pattern of
thymosin-beta 4 gene expression suggests that it may play a fundamentalrole in
the host defense mechanism


Melantan

LL-37

DESCRIPTION

LL-37 Is an anti-microbial peptide which belongs to the cathelicidin family of
AMPs(anti-microbial peptides). LL-37, like cathelicidins, are stored in neutrophil
granules as inactive precursors and are released as mature peptides when
neutrophils are stimulated. LL-37 is expressed in various cells and tissues such as
circulating neutrophils and myeloid bone marrow cells, epithelial cells of the skin, and
is also expressed in the gastrointestinal tract, as well as in the epididymis and lungs.
Moreover, production of LL-37 in macrophages is stimulated by vitamin D released
by sunlight through the skin. LL-37 plays an important role in the first line of defense
against infection and systemic invasion of pathogens at sites of inflammation and
wound. It is cytotoxic to both bacterial and normal eukaryotic cells and is significantly
resistant to proteolytic degradation in solution. LL-37 shows a broad spectrum of
antimicrobial activity against bacteria, enveloped viruses, and fungi. It has also
demonstrated success in helping promote wound healing and it may play a negative
role in atopic dermatitis and apsoriasis.

PROTOCOL

Content & Potency: 200mg capsules provided in quantities of 90
Suggested dosage: Varies with indication and patient

CLINICAL RESEARCH

Membrane Core-Specific Antimicrobial Action of Cathelicidin LL-37 Peptide
Switches Between Pore and Nanofibre Formation

 

Membrane-disrupting antimicrobial peptides provide broad-spectrum defence
against localized bacterial invasion in a range of hosts including humans. The most
generally held consensus is that targeting to pathogens is based on interactions
with the head groups of membrane lipids. Here we show that the action of LL-37, a
human antimicrobial peptide switches the mode of action based on the structure of
the alkyl chains, and not the head groups of the membrane forming lipids. We
demonstrate that LL-37 exhibits two distinct interaction pathways: pore formation in
bilayers of unsaturated phospholipids and membrane modulation with saturated
phospholipids. Uniquely, the membrane modulation yields helical-rich fibrous
peptide-lipid superstructures. Our results point at alternative design strategies for
peptide antimicrobials.


Semax

NUEROPEPTIDE

DESCRIPTION

It is well known that ACTH/MSH-like peptides (melanocortins) exert pleiotropic
non-hormonal actions among their larger activities. Melanocortins aect learning
processes and exploratory behavior, regeneration and development, nociceptive and
inflammatory processes, accelerate nerve regeneration and improve neuromuscular
performance. Together these classes of peptides control many behaviors such as
regulating attention, processes of learning, and memory formation as a result of their
pronounced effect on CNS functions. Heptapeptide SEMAX (MEHFPGP) is the
analogue of ACTH (4-10) that has prolonged neurotropic activity and thus is a good
candidate for medical therapy. Currently this peptide is successfully used in
treatment of patients with pathologies related to brain circulation dysfunction and with
different intellectual-amnestic problems of the CNS. Doctors have prescribed it for
many conditions like anxiety, memory improvement, ischemic events, stroke, nerve
regeneration, ADHD, opioid withdrawal, and even chronic diseases such as ALS,
Parkinson’s, and Alzheimer’s. Some doctors use it as a preventative measure to
protect against chronic disease and to acutely help improve memory and learning
processes. It also has a marked antithrombotic and fibrinolytic effect and a gastric
protective effect. It has also been suggested in literature that due to its effect on
carboxypeptidase it can also increase physical performance and adaptation
capacities in exposure to high intensity exercise. At its higher doses, .5mg/kg can
even be analgesic.

PROTOCOL

Content & Potency: 1 x 5mL Nasal applicator at 7.5mg/ml
Suggested dosage: Two squirts of 0.10ml ( 750mcg) nasally every day
Often prescribed for: Anti-Thromobosis, ADHD/Learning, Gastric protection, Physical
exertion improvedment pain, Metal toxicities.


PEG-MGF

MECHANO GROWTH FACTOR

DESCRIPTION

MGF is a split variant of IGF-1 but its sequence differs from the systemic IGF-1
produced by the liver. IGF-I is spliced towards MGF which initiates hypertrophy and
repair of local muscle damage. MGF is expressed by mechanically overloaded
muscle and is involved in tissue repair and adaptation. It is expressed as a pulse
following muscle damage and is involved in the activation of muscle satellite (stem)
cells. These donate nuclei to the muscle fibers that are required for repair and for the
hypertrophy process, which may have similar regulatory mechanisms (Goldspink, G.,
2005 p22). MGF is essential for repair and therefore growth of new cells, similar to
IGF-1. If MGF is not PEGylated, the half-life is several minutes therefore PEGylated
MGF must be considered during the compounding process to ensure an appropriate
half-life, thereby increasing duration of action.

PROTOCOL

Content & Potency: 1 x 3mL at 2000mcg/ml ready-to-inject subcutaneous.
Suggested dosage: 0.10ml daily for 5 days out of 7 (1 month supply).

CLINICAL RESEARCH

A.Philippou1, E. Papageorgiou1, G. Bogdanis2, A. Halapas1, A. Sourla3, m.
Maridaki, N. Pissimissis Source: Department of Experimental Physiology, Medical
School, National and Kapodistrian University of Athens.

Abstract: Different insulin-like growth factor-1 (IGF-1) isoforms, namely IGF-1Eb
and IGF-1Ec (MGF),have been proposed to have various functions in muscle repair
and growth. To gain insight into the potentially differential actions of IGF-1 isoforms
in the regulation of muscle regeneration, we assessed the time course of their
expressions at both mRNA and protein levels after exercise-induced muscle
damage in humans. In addition, we characterized mature IGF-1 and synthetic MGF
E peptide signalling in C2C12 myoblast-like cells in vitro. Ten healthy male
volunteers were subjected to exercise-induced muscle damage and biopsy
samples were taken from the exercised muscles before and 6 h, 2,5 and 16 days
post exercise. Muscle damage was documented by specific functional and
biochemical responses post exercise. PCR-based analyses of muscle biopsy
samples revealed a rapid and transient up-regulation of MGF mRNA expression
which was followed by a prolonged increase of IGF-1Ea and IGF-1Eb mRNA
expression (p<0.05). Patterns similar to those for mRNA expression were detected
for MGF and IGF-1Ea expression at the protein level. The action of synthetic MGF
E peptide differed from that of mature IGF1 since its proliferative effect on C2C12
myoblast-like cells was not blocked by an anti-IGF-1 receptor neutralizing antibody
and it did not phosphorylate Akt. Therefore, we conclude that the differential
expression profile of IGF-1 isoforms in vivo and the possible IGF-1R- independent
MGF E peptide signalling in skeletal muscle-like cells in vitro support the notion that
tissue-specific mRNA expression of MGF isoform produces mature IGF-1 and MGF
E peptides which possibly act as distinct mitogens in skeletal muscle regeneration.


AOD

9604 + HA

DESCRIPTION

AOD9604 is the a GH fragment which comprised the last 16 amino acids of the larger
growth hormone molecule. Although originally studies for fat loss, further studies
have transitioned it for regenerative medicine. In combination with hyaluronic acid
(HA), it is now being used to help regenerate hyaline cartilage and is showing strong
efficacy in the treatment of osteoarthritis. The combination acts to enhance the
differentiation of adipose mesenchymal stem cells into bone, promote proteoglycan
and collagen production in chondrocytes, and promote differentiation of myoblasts
into C2C12 cells; all of which are essential for bone, cartilage, and muscle repair.
These studies indicate that it has stronger therapeutic benefits compared to Bone
Marrow Aspirate Concentrate (BMAC) and Platelet Rich Plasma (PRP) therapy,
which have also been emerging as candidates for osteoarthritis medications.

AOD9604 + HA has proceeded to human WOMAC trials which allow the combination
to be investigated for on an osteoarthritis index which considers pain, stiness, and

PROTOCOL

Content & Potency: 5ml vials – 3000mcg/ml AOD (HMW HA)
Suggested dosage: .5ml-.75mls injected intra-articularly once a week for 4 weeks
and then once/month for 5 months


Tesamorelin

SubName

DESCRIPTION

Tesamorelin is a growth hormone releasing hormone analog that has been shown to
increase IGF-1 levels in men by an average of 181 micrograms/liter. It binds and
stimulates GHRH receptors with similar potency as endogenous GHRH. It has a host
of other benefits including nootropic effects and reducing triglycerides.

Tesamorelin has subsequently been shown to decrease carotid intima media
thickness (cIMT), Visceral adipose tissue (VAT), and C-reactive protein (CRP) in a
recent study. It has not been shown to significantly affect other pituitary hormones
and their respective mechanisms in the body. Additionally, it has been shown to
improve cognitive function for healthy older adults and also for people with mild
cognitive

PROTOCOL

Content & Potency: 24 1mg lyophilized vials, 10ml vial of sterile water for
reconstitution
Suggested dosage: 1 mg injected subcutaneously before bed about 90 minutes
after last food intake

CLINICAL RESEARCH

The Procognitive and Synaptogenic Effects of Angiotensin IV–Derived
Peptides Are Dependent on Activation of the Hepatocyte Growth Factor/c-Met
System

A subset of angiotensin IV (AngIV)–related molecules are known to possess
procognitive/antidementia properties and have been considered as templates for
potential therapeutics. However, this potential has not been realized because of
two factors: 1) a lack of blood-brain barrier–penetrant analogs, and 2) the absence
of a validated mechanism of action. The pharmacokinetic barrier has recently been
overcome with the synthesis of the orally active, blood-brain barrier–permeable
analog N-hexanoic-tyrosine-isoleucine-(6) aminohexanoic amide (dihexa).
Therefore, the goal of this study was to elucidate the mechanism that underlies
dihexa’s procognitive activity. Here, we demonstrate that dihexa binds with high
affinity to hepatocyte growth factor (HGF) and both dihexa and its parent
compound Norleucine 1-AngIV (Nle1-AngIV) induce c-Met phosphorylation in the
presence of subthreshold concentrations of HGF and augment HGF-dependent cell
scattering. Further, dihexa and Nle1-AngIV induce hippocampal spinogenesis and
synaptogenesis similar to HGF itself. These actions were inhibited by an HGF
antagonist and a short hairpin RNA directed at c-Met. Most importantly, the
procognitive/antidementia capacity of orally delivered dihexa was blocked by an
HGF antagonist delivered intracerebroventricularly as measured using the Morris
water maze task of spatial learning.