NOESY NMR spectrum of the collagen hydrolysate Fortigel ® from Gelita applied in our dog study. F1 and F2 are the frequency axes which display both the chemical shifts of the aromatic-and NH-region of the collagen protons (in ppm).

NOESY NMR spectrum of the collagen hydrolysate Fortigel ® from Gelita applied in our dog study. F1 and F2 are the frequency axes which display both the chemical shifts of the aromatic-and NH-region of the collagen protons (in ppm).

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Osteoarthritis belongs to the most common joint diseases in humans and animals and shows increased incidence in older patients. The bioactivities of collagen hydrolysates, sulfated glucosamine and a special fatty acid enriched dog-food were tested in a dog patient study of 52 dogs as potential therapeutic treatment options in early osteoarthritis....

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... data were recorded from each dog at the beginning of the study. There was no significant statistical deviation in the x-ray data when comparing the left with the right hip joint ( Figure S6). This is also the case when comparing the left and the right knee joint (p-value left knee joint: 0.12; right knee joint: 0.13; left hip joint: 0.11; right hip joint: 0.15). ...
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... the collagen hydrolysates differed in their composition, we further characterized them to provide a more detailed molecular analysis. In the present study, we used TOCSY and NOESY experiments to identify specific amino acid residues (e.g., Arg residues) of these bio-active compounds ( Figure 6). This type of analysis allowed us to characterize the collagen hydrolysate unambiguously. ...
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... of running marks of the dog patients as revealed by the patient-holders. Figure S6. X-ray data of the left and right femoral joints (A left; B right) obtained from each dog at the beginning of the study. ...

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... As of now, researchers have identified and categorized 29 types of collagen. These types vary mainly in their structure, but also in their properties and distribution within the body [8]. Most studies focus on fibrillar collagen-in this regard, collagen types I, II, III, V, XI, XXIV, and XXVII are distinguished-and it accounts for about 90% of the collagen mass in the human body. ...
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In the present study, the effect of the addition of quince and collagen type I and III to dessert chocolate on its functional properties was determined. The study evaluated the antioxidant potential of the tested formulations using the FRAP method and the linoleic acid oxidation test and beta-carotene bleaching test. The tested samples were also evaluated for inhibitory activity against enzymes important in preventive health (inflammation and neurodegenerative disorders) namely: AChE, BChE, GR, GPx, COX, and SOD. The addition of quince and collagen to the chocolate samples resulted in higher activity compared to the control sample, as indicated by the FRAP test. The experiment highlighted the impact of including quince fruit on the antioxidant activity of the chocolate samples. Interestingly, merely increasing the quince fruit amount did not consistently enhance antioxidant potential. Specifically, chocolate samples with a lower proportion of quince fruit (2 g/100 g) exhibited greater antioxidant activity when supplemented with collagen I. Conversely, in samples with higher quince percentages (3 g and 4 g), those enriched with collagen III showed higher antioxidant activity. Similar correlations were observed in the linoleic acid oxidation test. Notably, samples containing 3 g and 4 g of quince and type III collagen demonstrated statistically similar highest antioxidant properties. Regardless of the collagen type used, there was no observed increase in activity towards the tested enzymes for samples with the lowest percentage of quince fruit. Both collagen types exhibited the highest activity in the inhibition assay against acetylcholinesterase and butyrylcholinesterase when combined with 3 g and 4 g of quince. Overall, the experimental incorporation of both fruit and collagen enhanced the chocolates’ activity. Similarly to the antioxidant activity findings, chocolates with lower quince fruit quantities showed increased activity when supplemented with collagen III, while those with higher quince content (3 g and 4 g) displayed higher activity with collagen I. Bitter chocolate by itself is an attractive food product, rich in many bioactive compounds. However, enriching it with other attractive raw materials can make its properties and taste even more attractive.
... The deep-water ocean fish's skin is rich in collagen. It's hydrolysate when administered to arthritic dogs, reduced the levels of MMP-3 and improved their pain and lameness [145]. Fish cartilage and skin peptides also increased types I and II collagen protein synthesis mechanism while suppressing both transcription and expression of inflammatory proteases [136]. ...
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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects the joints of the human body and is projected to have a prevalence age-standardized rate of 1.5 million new cases worldwide by 2030. Several conventional and non-conventional preventive and therapeutic interventions have been suggested but they have their side effects including nausea, abdominal pain, liver damage, ulcers, heightened blood pressure, coagulation, and bleeding. Interestingly, several food-derived peptides (FDPs) from both plant and animal sources are increasingly gaining a reputation for their potential in the management or therapy of RA with little or no side effects. In this review, the concept of inflammation, its major types (acute and chronic), and RA identified as a chronic type were discussed based on its pathogenesis and pathophysiology. The conventional treatment options for RA were briefly outlined as the backdrop of introducing the FDPs that potentiate therapeutic effects in the management of RA.
... Purified bioactive extracts of small sea fish: a promising therapy for posttraumatic osteoarthritis Chondroitin sulphates are present in high concentrations in bioactive extracts derived from certain fish species. In vitro studies have demonstrated that CSs obtained from fish possess a broad spectrum of pharmacological activities, including antioxidant effects (derived from tilapia viscera as well as salmon, shark, and ray cartilage), anticoagulant, anti-platelet, and thrombolytic effects (derived from Nile tilapia and pacu viscera, sturgeon skull, and backbone), anticancer effects (derived from grey triggerfish and smooth-hound skins), anti-obesity effects (derived from skate), anti-inflammatory and anti-dyslipidaemic effects (derived from skate cartilage), wound healing effects (derived from sturgeon cartilage and backbone), neuroprotective effects (derived from shark cartilage), and chondroprotective effects (derived from small spotted catshark, blue shark, thornback skate, and small sea fish) [68,[79][80][81][82][83]. ...
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Post-traumatic osteoarthritis (PTOA), a disorder of the synovium, subchondral bone, and cartilage that affects the entire joint, constitutes approximately 12% of all cases of symptomatic osteoarthritis. This review summarizes the pathogenetic mechanisms that underlie the positive influence of chondroitin sulphates (CSs) on PTOA as means of preventive and therapeutic treatment. Mechanisms of PTOA development involve chondrocytes undergoing various forms of cell death (apoptosis, pyroptosis, necroptosis, ferroptosis and/or necrosis). Chondroitin sulphates are a class of glycosaminoglycans that improve the structure and function of cartilage and subchondral bone, which is associated with their ability to decrease the activation of NF-κB and p38 MAPK, and up-regulate Nrf2. Standardized small fish extract (SSFE) is an example of the drugs that can attenuate NF-κB-mediated systemic inflammation, potentially helping to reduce joint inflammation and cartilage degradation, improve joint function, and alleviate pain and disability in patients with these conditions.
... Molecular modeling simulations were employed to further evaluate the contact efficacy of collagen fragments and glucosamines with protein receptor architectures. There are potential advantages of using lipids, particularly eicosapentaenoic acid (extracted from fish oil), sulfated glycans (such as sulfated glucosamine from crabs and mussels), and collagen hydrolysates on biochemical and physiological processes for applications in dietary supplements for human and veterinary medicine [12]. ...
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Besides the importance of our oceans as oxygen factories, food providers, shipping pathways, and tourism enablers, oceans hide an unprecedented wealth of opportunities [...]
... Among them, collagen has demonstrated an ability to prevent cartilage destruction [10]. Mechanism of action is based on the production of macromolecules and inhibition of catabolic enzymes, therefore increasing the synthesis of collagen type II and reducing inflammation [10]. ...
... Among them, collagen has demonstrated an ability to prevent cartilage destruction [10]. Mechanism of action is based on the production of macromolecules and inhibition of catabolic enzymes, therefore increasing the synthesis of collagen type II and reducing inflammation [10]. Oral tolerance phenomenon of this nutraceutical also leads to elevated levels of 17 collagen-derived peptides transiently in the blood, with a particular enrichment in Gly-Pro-Hyp [11], that involves activation of regulatory T cells (Tregs) [12]. ...
... NMR studies supported by molecular modeling calculations enable a detailed analysis of the interactions between proteins or peptides with other biomolecules [26][27][28][29][30], lipids [8,26,31,32] oligosaccharides or glycoconjugates [18][19][20]33] under various physiological conditions. This strategy was previously successfully applied when collagen fragments and sulfated glucosamines were tested and compared in relation to their receptors [34][35][36][37][38]. ...
... It is now of importance to find out in which way the insights obtained by clinical observations and molecular modeling can be verified with the help of NMR experiments. In this context, it is important to mention that collagen hydrolysates, which are mixtures of linear peptides and short collagen fragments, have been successfully studied by various NMR methods [34][35][36][37][38]. Clinically, they are orally administered and serve to act as chondroprotective agents in patient target tissues. ...
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The global outbreak of SARS-CoV-2/COVID-19 provided the stage to accumulate an enormous biomedical data set and an opportunity as well as a challenge to test new concepts and strategies to combat the pandemic. New research and molecular medical protocols may be deployed in different scientific fields, e.g., glycobiology, nanopharmacology, or nanomedicine. We correlated clinical biomedical data derived from patients in intensive care units with structural biology and biophysical data from NMR and/or CAMM (computer-aided molecular modeling). Consequently, new diagnostic and therapeutic approaches against SARS-CoV-2 were evaluated. Specifically, we tested the suitability of incretin mimetics with one or two pH-sensitive amino acid residues as potential drugs to prevent or cure long-COVID symptoms. Blood pH values in correlation with temperature alterations in patient bodies were of clinical importance. The effects of biophysical parameters such as temperature and pH value variation in relation to physical-chemical membrane properties (e.g., glycosylation state, affinity of certain amino acid sequences to sialic acids as well as other carbohydrate residues and lipid structures) provided helpful hints in identifying a potential Achilles heel against long COVID. In silico CAMM methods and in vitro NMR experiments (including 31P NMR measurements) were applied to analyze the structural behavior of incretin mimetics and SARS-CoV fusion peptides interacting with dodecylphosphocholine (DPC) micelles. These supramolecular complexes were analyzed under physiological conditions by 1H and 31P NMR techniques. We were able to observe characteristic interaction states of incretin mimetics, SARS-CoV fusion peptides and DPC membranes. Novel interaction profiles (indicated, e.g., by 31P NMR signal splitting) were detected. Furthermore, we evaluated GM1 gangliosides and sialic acid-coated silica nanoparticles in complex with DPC micelles in order to create a simple virus host cell membrane model. This is a first step in exploring the structure–function relationship between the SARS-CoV-2 spike protein and incretin mimetics with conserved pH-sensitive histidine residues in their carbohydrate recognition domains as found in galectins. The applied methods were effective in identifying peptide sequences as well as certain carbohydrate moieties with the potential to protect the blood–brain barrier (BBB). These clinically relevant observations on low blood pH values in fatal COVID-19 cases open routes for new therapeutic approaches, especially against long-COVID symptoms.
... Due to its low denaturation temperature (25-30 °C), the aqua-collagen degrades easily under body temperature conditions (Pallela et al. 2011;Tziveleka et al. 2017). In this respect, aqua-collagen was largely explored for food purposes and poorly explored for biomedical material applications (Eckert et al. 2021;Kumar and Rani 2017;Mahboob 2015). ...
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Collagen has been widely used as a biomaterial for tissue regeneration. At the present, aqua-collagen derived from fish is poorly explored for biomedical material applications due to its insufficient thermal stability. To improve the bone repair ability and thermal stability of fish collagen, the tilapia skin collagen was crosslinked by EDC/NHS with heparin to bind specifically to BMP-2. The thermal stability of tilapia skin collagen crosslinked with heparin (HC-COL) was detected by differential scanning calorimetry (DSC). Cytotoxicity of HC-COL was assessed by detecting MC3T3-E1 cell proliferation using CCK-8 assay. The specific binding of BMP-2 to HC-COL was tested and the bioactivity of BMP-2-loaded HC-COL (HC-COL-BMP-2) was evaluated in vitro by inducing MC3T3-E1 cell differentiation. In vivo, the bone repair ability of HC-COL-2 was evaluated using micro-CT and histological observation. After crosslinking by EDC/NHS, the heparin-linked and the thermostability of the collagen of Nile Tilapia were improved simultaneously. HC-COL has no cytotoxicity. In addition, the binding of BMP-2 to HC-COL was significantly increased. Furthermore, the in vitro study revealed the effective bioactivity of BMP-2 binding on HC-COL by inducing MC3T3-E1 cells with higher ALP activity and the formation of mineralized nodules. In vivo studies showed that more mineralized and mature bone formation was achieved in HC-COL-BMP-2 group. The prepared HC-COL was an effective BMP-2 binding carrier with enough thermal stability and could be a useful biomaterial for bone repair.
... Higher molecular weight collagen peptides obtained from skin of blue shark increased the mRNA level of collagen type I in human dermal fibroblast culture (Sanchez et al., 2018). Collagen hydrolysate made from the skin of deep water ocean fish could reduce MMP-3 levels, improve the lameness and reduce pain in dogs with early OA (Eckert et al., 2021). Oral administration of low-molecular-weight collagen peptide from the skin of Pangasius hypophthalmus ameliorated cartilage damage, reduced the loss of proteoglycan, suppressed the deterioration of the microstructure in tibial subchondral bone, upregulated type II collagen and downregulated MMP-13 in cartilage tissue. ...
... In addition, calcitonin can significantly increase SOD and decreased malondialdehyde, which could alleviate oxidation stress to prevent the progression of OA, while diclofenac sodium did not affect those factors (Adeyemi & Olayaki, 2017). In an OA dog experiment, collagen hydrolysate and sulfated glucosamine showed similar effect in reducing pain and lameness and improving quality of life scores (Eckert et al., 2021). Oral administration of Antarctic krill peptides at 600 mg/kg⋅bw showed similar efficiency with glucosamine in maintaining articular cartilage structure, including cartilage thickness, cartilage area and Osteoarthritis Research Society International semiquantitative scores. ...
Article
Background Bioactive peptides from different food protein have been reported to have a lot of biological activities, such as anti-inflammation and anti-oxidation, making them beneficial for chronic disease. Osteoarthritis (OA) is one of the major diseases affecting human health worldwide. The main treatment methods of OA are physiotherapy, medication and surgery. Many drug, such as adrenocortical hormone, have serious side effects on the patients. Therefore, it is necessary to search for treatment with less side effects. Recently, biologically active peptides from natural foods have been extensively reported to show beneficial effects on alleviating symptom of osteoarthritis, which make it potential for industrial application in the functional foods. Scope and approach In this review, we focus on biological characteristics of food-derived peptides, especially their therapeutic effect in osteoarthritis, and the underlying mechanism by which these peptides exert the biologically function in osteoarthritis. Key findings and conclusions Peptides from bovine, chicken, deer are the predominant species for improvement of osteoarthritis in in vitro, in vivo and clinical studies. Marine food is another important protein source for production of bioactive peptide that showed beneficial effect in the treatment of osteoarthritis. A few peptides from plant protein such as soybean also showed positive effect on chondrocytes. However, many bioactive peptides that showed the beneficial effect on osteoarthritis were in the form of mixture. Finding out the exact peptide that exerts the positive effect in the osteoarthritis is necessary for the industrial application in the future.
... Cosmetics, biomedicines and functional foods [173] Marine (commercial drug Fortigel ® by Gelita AG, Eberbach, Germany) Combined chemical and enzymatic Chondroprotective properties Osteoarthritis treatment [174] Not specified (commercial drug Bodybalance ® by Gelita AG, Eberbach, Germany) Combined chemical and enzymatic Improving body composition and regional muscle strength Biologically active additives (functional foods) [175][176][177] Blue shark Prionace glauca Enzymatic (papain, alcalase) ...
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Currently, the growth of the global population leads to an increase in demand for agricultural products. Expanding the obtaining and consumption of food products results in a scale up in the amount of by-products formed, the development of processing methods for which is becoming an urgent task of modern science. Collagen and keratin make up a significant part of the animal origin protein waste, and the potential for their biotechnological application is almost inexhaustible. The specific fibrillar structure allows collagen and keratin to be in demand in bioengineering in various forms and formats, as a basis for obtaining hydrogels, nanoparticles and scaffolds for regenerative medicine and targeted drug delivery, films for the development of biodegradable packaging materials, etc. This review describes the variety of sustainable sources of collagen and keratin and the beneficial application multiformity of these proteins.
... Collagen hydrolysates have been effectively utilized due to their good moisturizing properties at the stratum corneum layer of the skin, which reduce the effects of skin dryness, laxity and wrinkles [45]. Eckert et al. (2021) reported that collagen hydrolysates of fish, jellyfish and bovine origin that were used as food supplements could maintain cartilage health of dogs and could be as potential therapeutic drugs in early osteoarthritis [46]. Schadow et al. (2017) used several collagen hydrolysates as nutraceuticals for human osteoarthritis, and found that there were marked differences between collagen hydrolysates of different origins [47]. ...
... Collagen hydrolysates have been effectively utilized due to their good moisturizing properties at the stratum corneum layer of the skin, which reduce the effects of skin dryness, laxity and wrinkles [45]. Eckert et al. (2021) reported that collagen hydrolysates of fish, jellyfish and bovine origin that were used as food supplements could maintain cartilage health of dogs and could be as potential therapeutic drugs in early osteoarthritis [46]. Schadow et al. (2017) used several collagen hydrolysates as nutraceuticals for human osteoarthritis, and found that there were marked differences between collagen hydrolysates of different origins [47]. ...
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Bovine bone is rich in collagen and is a good material for collagen peptide preparation. Although thermolysin-like proteases (TLPs) have been applied in different fields, the potential of TLPs in preparing bioactive collagen peptides has rarely been evaluated. Here, we characterized a thermophilic TLP, A69, from a hydrothermal bacterium Anoxybacillus caldiproteolyticus 1A02591, and evaluated its potential in preparing bioactive collagen peptides. A69 showed the highest activity at 60 °C and pH 7.0. We optimized the conditions for bovine bone collagen hydrolysis and set up a process with high hydrolysis efficiency (99.4%) to prepare bovine bone collagen peptides, in which bovine bone collagen was hydrolyzed at 60 °C for 2 h with an enzyme–substrate ratio of 25 U/g. The hydrolysate contained 96.5% peptides that have a broad molecular weight distribution below 10000 Da. The hydrolysate showed good moisture-retention ability and a high hydroxyl radical (•OH) scavenging ratio of 73.2%, suggesting that the prepared collagen peptides have good antioxidative activity. Altogether, these results indicate that the thermophilic TLP A69 has promising potential in the preparation of bioactive collagen peptides, which may have potentials in cosmetics, food and pharmaceutical industries. This study lays a foundation for the high-valued utilization of bovine bone collagen.