An oligopeptide derived from angiotensin IV that binds to HGF and potentiates its activity at c-Met receptor, promoting neurogenesis and cognitive function.
Benoist. Caroline C CC; Kawas. Leen H LH; Zhu. Mingyan M; Tyson. Katherine A KA; Stillmaker. Lori L;...
Researchers found that dihexa, a small peptide you can take by mouth, can cross the brain barrier and boost brain signaling through the HGF/c-Met pathway. In mouse experiments it helped grow new brain connections and improved performance on a memory test, and these effects disappeared when the HGF system was blocked.
Wells. Russell G RG; Azzam. Azzam F AF; Hiller. Amie L AL; Sardinia. Michael F MF
In a rat study that mimics Huntington's disease, the peptide Dihexa (also called PNB-0408) was given to see if it could protect the brain and keep the animals healthy. The toxin 3‑NP made the rats gain less weight, move poorly, and have trouble learning. Dihexa did not stop any of these problems, suggesting it isn’t effective for this type of Huntington’s‑like damage in rats.
Sun. Xiaojin X; Deng. Yang Y; Fu. Xinxin X; Wang. Siyu S; Duan. Rui R; Zhang. Yingdong Y
In a mouse model of Alzheimer's, an oral peptide called Dihexa boosted a brain hormone (AngIV), improved memory in maze tests, and lowered brain inflammation by turning on the PI3K/AKT pathway. The benefits disappeared when the pathway was blocked, showing it’s likely the key mechanism.
Weiss. Jessica B JB; Phillips. Cody J CJ; Malin. Edward W EW; Gorantla. Vijay S VS; Harding. Joseph...
In rats with a cut sciatic nerve, giving a mix of stem cells, a growth factor (G‑CSF), or the peptide Dihexa helped the leg muscles work better after surgery. All the rats got their feeling back in about 8 weeks, but the groups that got stem cells plus Dihexa (or G‑CSF) showed noticeably better walking ability than the others.
Wright. John W JW; Kawas. Leen H LH; Harding. Joseph W JW
Researchers made a new, stable version of the brain peptide AngIV called Dihexa that can get into the brain and help form new synapses, which in animal studies improved memory and movement problems linked to Alzheimer’s and Parkinson’s.
Animal studies show that the brain hormone Ang IV and its cousins (including the experimental peptide dihexa) can boost memory and learning in rats, especially when given right before a test. A similar brain peptide, Ang‑(1‑7), also helped memory in a few studies. However, the benefits were seen when the compounds were injected directly into the brain, which isn’t practical for everyday use.
The paper reviews a new brain‑targeting molecule called Dihexa that can activate the HGF/c‑Met system, which helps neurons grow and form new connections. In animal studies Dihexa improved memory and reduced Alzheimer‑like damage, and it can be taken by mouth and cross into the brain. However, no human trials or dosing guidelines are available yet.
Pan. Tingcai T; Wang. Ning N; Zhang. Jiaye J; Yang. Fan F; Chen. Yan Y; Zhuang. Yuanqi Y; Xu. Yingyi...
Scientists found that a mix of cheap chemicals, including the peptide dihexa, can turn stem cells into liver‑like cells in the lab without using expensive growth factors. This method works well for making lots of functional liver cells for research or therapy, but it isn’t a recipe you can use on yourself.
McCoy. Alene T AT; Benoist. Caroline C CC; Wright. John W JW; Kawas. Leen H LH; Bule-Ghogare. Jyote...
Angiotensin IV (AngIV: VYIHPF)-related peptides have long been recognized as procognitive agents with potential as antidementia therapeutics. Their development as useful therapeutics, however, has been limited by physiochemical properties that make them susceptible to metabolic degradation and impermeable to gut and blood-brain barriers. A previous study demonstrated that the core structural information required to impart the procognitive activity of the AngIV analog, norleucine(1)-angiotensin IV, resides in its three N-terminal amino acids, Nle-Tyr-Ile. The goal of this project was to chemically modify this tripeptide in such a way to enhance its metabolic stability and barrier permeability to produce a drug candidate with potential clinical utility. Initial results demonstrated that several N- and C-terminal modifications lead to dramatically improved stability while maintaining the capability to reverse scopolamine-induced deficits in Morris water maze performance and augment hippocampal synaptogenesis. Subsequent chemical modifications, which were designed to increase hydrophobicity and decrease hydrogen bonding, yielded an orally active, blood-barrier permeant, metabolically stabilized analog, N-hexanoic-Tyr-Ile-(6) aminohexanoic amide (dihexa), that exhibits excellent antidementia activity in the scopolamine and aged rat models and marked synaptogenic activity. These data suggest that dihexa may have therapeutic potential as a treatment of disorders, such as Alzheimer's disease, where augmented synaptic connectivity may be beneficial.
Nowotarska. Stella W SW; Nowotarski. Krzysztof J KJ; Friedman. Mendel M; Situ. Chen C
Monolayers composed of bacterial phospholipids were used as model membranes to study interactions of the naturally occurring phenolic compounds 2,5-dihydroxybenzaldehyde and 2-hydroxy-5-methoxybenzaldehyde, and the plant essential oil compounds carvacrol, cinnamaldehyde, and geraniol, previously found to be active against both Gram-positive and Gram-negative pathogenic microorganisms. The lipid monolayers consist of 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (DPPE), 1,2-dihexa- decanoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG), and 1,1',2,2'-tetratetradecanoyl cardiolipin (cardiolipin). Surface pressure-area (π-A) and surface potential-area (Δψ-A) isotherms were measured to monitor changes in the thermodynamic and physical properties of the lipid monolayers. Results of the study indicated that the five compounds modified the three lipid monolayer structures by integrating into the monolayer, forming aggregates of antimicrobial -lipid complexes, reducing the packing effectiveness of the lipids, increasing the membrane fluidity, and altering the total dipole moment in the monolayer membrane model. The interactions of the five antimicrobial compounds with bacterial phospholipids depended on both the structure of the antimicrobials and the composition of the monolayers. The observed experimental results provide insight into the mechanism of the molecular interactions between naturally-occurring antimicrobial compounds and phospholipids of the bacterial cell membrane that govern activities.
Mathapati. Santosh S; Siller. Richard R; Impellizzeri. Agata A R AA; Lycke. Max M; Vegheim. Karianne...
Hepatocyte-like cells (HLCs) generated in vitro from human pluripotent stem cells (hPSCs) provide an invaluable resource for basic research, regenerative medicine, drug screening, toxicology, and modeling of liver disease and development. This unit describes a small-molecule-driven protocol for in vitro differentiation of hPSCs into HLCs without the use of growth factors. hPSCs are coaxed through a developmentally relevant route via the primitive streak to definitive endoderm (DE) using the small molecule CHIR99021 (a Wnt agonist), replacing the conventional growth factors Wnt3A and activin A. The small-molecule-derived DE is then differentiated to hepatoblast-like cells in the presence of dimethyl sulfoxide. The resulting hepatoblasts are then differentiated to HLCs with N-hexanoic-Tyr, Ile-6 aminohexanoic amide (Dihexa, a hepatocyte growth factor agonist) and dexamethasone. The protocol provides an efficient and reproducible procedure for differentiation of hPSCs into HLCs utilizing small molecules. © 2016 by John Wiley & Sons, Inc.
Uribe. Phillip M PM; Kawas. Leen H LH; Harding. Joseph W JW; Coffin. Allison B AB
This study shows that a small molecule called Dihexa can protect the tiny hearing cells in zebrafish from damage caused by common antibiotics like gentamicin and neomycin. It works by activating the body’s natural HGF signaling pathway inside the cells, not by stopping the drug from entering them. The best protection was seen at a very low dose (about 1 µM) and the effect goes away if the HGF pathway is blocked.
Bapst. Jean-Philippe JP; Froidevaux. Sylvie S; Calame. Martine M; Tanner. Heidi H; Eberle. Alex N AN
Scientists made special versions of a skin‑pigment hormone (alpha‑MSH) that stick better to melanoma cells in a dish, but when they tried them in mice they didn’t reach the tumors well and got stuck in the kidneys, making them worse than the original version for imaging cancer.
The study describes a lab technique for making tiny filters in artificial cell membranes using special lipids that can be hardened with UV light. It shows how changing the mix of two lipids changes the size of openings that let different membrane‑bound molecules pass. The work is purely methodological and does not involve the peptide dihexa or any health‑related application.
Kessel. David D; Conley. Mary M; Vicente. M Graça H MG; Reiners. John J JJ
This study was designed to provide more detailed information on the subcellular sites of binding of the porphycene, termed 9-capronyloxytetrakis (methoxyethyl) porphycene (CPO), with a fluorescence resonance energy transfer (FRET) technique. The proximity of CPO to two fluorescent probes was determined: nonyl acridine orange (NAO), a dye with specific affinity for the mitochondrial lipid cardiolipin, and dihexa-oxacarbocyanine iodide (DiOC6), an agent that labels the endoplasmic reticulum (ER). FRET spectra indicated energy transfer between DiOC6 and CPO but no significant transfer between NAO and CPO. These results confirm data obtained by fluorescence microscopy, suggesting a similar pattern of subcellular localization by CPO and DiOC6 but not by CPO and NAO. However, when cells containing CPO were irradiated and then loaded with NAO, FRET between the two fluorophores was observed. Hence, a relocalization of CPO can occur during irradiation. These data provide an explanation for recent studies on CPO-catalyzed photodamage to both ER and mitochondrial Bcl-2.
Localization of surfactant phospholipid clearance in lung cells was investigated in vivo in rabbits using radiolabeled dipalmitoylphosphatidylcholine (DPPC) and 1,2-dihexa-decyl-sn-glycero-3-phosphocholine (DPPC-ether), a phospholipase A1- and A2-resistant analogue of DPPC. After intratracheal injection of liposomes of the labeled lipids associated with unlabeled surfactant, adult rabbits were killed in groups of three to five at 0, 4, 12, and 24 h with recovery of bronchoalveolar lavages for alveolar macrophages and surfactant. Type II cells and tissue-associated macrophages were isolated on Percoll gradients following elastase and trypsin digestion of the lungs. Radiolabel recoveries as saturated phosphatidylcholine were measured in alveolar wash, alveolar macrophages, lung tissue, and the type II cell and mixed cell bands from the Percoll gradients. Cost accounting of label demonstrated similar recoveries at 0 h, but significantly more DPPC-ether compared with DPPC in cells at later times, indicating ineffective degradation of the DPPC-ether. Internalization of the lung tissue-associated labels into cells was time dependent. At all times, greater than 65% of the cell-associated labels were recovered in type II cells, indicating the primary role for these cells in clearing alveolar surfactant phospholipid in vivo. The total contribution of alveolar macrophages to the overall clearance was approximately 20%.
Siller. Richard R; Greenhough. Sebastian S; Naumovska. Elena E; Sullivan. Gareth J GJ
This study describes a lab method that uses small chemicals to turn stem cells into liver‑like cells. It’s a technical protocol for researchers and does not give any advice on taking a peptide or supplement for health or performance.