Immune Regulation, Enhancement of Neural and Cognitive Function and Improvement of Skin-" Bird's Nest Peptide"

Bird's nest is a nest formed by the saliva secreted by six species of swiftlets in the genus Swiftlet during the breeding season or the condensation of saliva and its feathers. Southeast Asian countries such as Malaysia, Indonesia and Thailand are rich in bird's nest. From the perspective of composition, bird's nest is a relatively comprehensive food with an average protein content of 50% to 55% of the total dry weight, followed by carbohydrates, minerals and fats. The main carbohydrate in a bird's nest is sialic acid (SA), the average content is 10%, the essential trace elements include calcium, phosphorus, iron, sodium, potassium and iodine, and the essential amino acids include phenylalanine, methionine, lysine, leucine, isoleucine, threonine and valine.

In addition, active substances similar to epidermal growth factor (EGF) and trace hormones were found in bird's nests. The key ingredients mentioned above may have benefits for the general health of the general public, such as anti-influenza virus, immune regulation, improved intelligence and memory, improved neurodegenerative diseases, improved cell differentiation, antioxidant, and improved cardiovascular disease. According to the "Bird's Nest Industry White Paper", the domestic bird's nest consumption market will reach about 40 billion yuan in 2020, and women account for the majority of consumers, and women's love for bird's nest may come from the beauty, nourishing and conditioning effects of bird's nest. However, the benefits of bird's nest for different groups such as women, the elderly, and children still need to be supported by more sufficient and strong research evidence, including the physical basis and scientific principle of the investigation.

01 Health Benefits

Immunomodulation

At the level of collective cellular immunity, bird's nest can enhance the activity of T lymphocytes and B lymphocytes to some extent. In addition, animal experiments showed that bird's nest had effects on cellular immunity, humoral immunity and non-specific immunity of mice. The T lymphocyte transformation and serum IgM content of mice were significantly increased after intragastric administration of Pearl bird's nest extract. The splenic index, thymus index, serum hemolysin content, phagocytosis rate and phagocytosis index of peritoneal macrophages were significantly increased and the level of delayed allergic reaction was significantly decreased after 4 weeks of intragastric administration of bird's nest homogenate. Compared with the blank control group, the immune organ index and serum interleukin-2 (IL-2) content of the female rats were significantly increased after weaning with high dose of bird's nest homogenate during pregnancy and/or lactation. However, the target of positive immunomodulatory effects of bird's nest is not clear. In vitro fermentation of bird's nest glycoprotein using human colon model, Atopobium spp was found under the action of bird's nest glycopeptide. And Faecalibacterium prausnitzii have shown enhanced and extended growth curves. The former bacterium has been reported to be negatively correlated with inflammatory bowel disease (IBD), and the latter is the first discovered anti-inflammatory bacterium. The researchers found that bird's nest can regulate the gut flora of normal mice by supporting beneficial bacteria and inhibiting harmful bacteria. Therefore, bird's nest may play an immune-boosting role by regulating gut microecology, such as the flora associated with inflammation. At the same time, it was found that bird's nest hydrolysates (glycoproteins, glycopeptides) promoted the proliferation of Caco-2 cell lines in vitro, and macromolecular glycoproteins or glycopeptides were found to translocation through the single cell layer by paracellular transport. Therefore, bird's nest may also play an immunomodulatory role by influencing the intestinal epithelial cell barrier.

Enhanced neural and cognitive function

Advanced glycation end products (AGEs) are involved in the development and deterioration of many degenerative diseases, and the loss of cellular antioxidant mechanisms and the free radicals produced by AGEs may play an important role in the pathogenesis of aging and aging-related diseases. After the 12-week intervention experiment, there was no significant increase in serum AGEs content caused by estrogen deficiency in OV rats in bird's nest group, and it was found that bird's nest affected the REDOX status of OV rats through oxidative damage (malondialdehyde content) and antioxidant enzyme markers (superoxide dismutase and catalase). In addition, the expression of genes related to neurodegeneration and apoptosis was down-regulated in the hippocampus and frontal cortex of OV rats in the bird's nest group. These results suggest that bird's nest may mediate oxidative stress in OV rats by modifying the REDOX system of AGEs, and play a protective role in nerve damage caused by estrogen deficiency. In addition to participating in age-related neurodegenerative changes, the effect of bird's nest on cognitive function in OV rats found that bird's nest OV rats showed better spatial learning and memory ability in Morris water maze, which may be achieved by enhancing SIRT-1-mediated hippocampus neuroplasticity. In conclusion, although the specific cellular and molecular mechanisms of neurodegenerative diseases or cognitive dysfunction induced by estrogen deficiency are still unclear, it can be seen that bird's nest has a certain protective effect on nerve damage caused by estrogen deficiency, and it is expected to be applied to a new strategy to prevent or treat neurodegenerative diseases related to menopause.

Improve skin

The potential whitening activity of bird's nest was evaluated comprehensively using a cell model. First, the complex protein was fully broken into peptide by acid treatment and proteolytic hydrolysis, and the binding state SA was released. In the whitening experiment, the degree of inhibition of "digested" bird's nest products on melanin production and tyrosinase in B16 cells was higher than that of "undigested" bird's nest. In addition, HepG2 cell model also showed that the "digested" products of bird's nest had significant antioxidant capacity and protective effect on cell oxidative damage caused by H2O2. After the data were processed by the contribution rate analysis method, the results showed that the contribution rate of the protein components in the enzymatic hydrolysis products of bird's nest reached 85.87%, and the contribution rate of free SA to the inhibition of tyrosinase activity accounted for 63.43%. It was concluded that bird's nest protein peptide and free SA mainly played antioxidant and tyrosinase inhibitory activities in alleviating melanin pigmentation, respectively. In addition, to verify whether bird's nest has a moisturizing effect on the skin and to explore the possible mechanism, the researchers explored the expression of filaggrin in the keratinocyte HaCaT line. On the surface of the skin, the epidermal stratum corneum retains moisture through natural moisturizing factors, more than 70% of which are synthesized and derived from filaggrin. The expression of filaggrin and filaggrin 2 in mRNA and protein levels was significantly increased by enzymolysis of bird's nest extract in a dose-dependent manner. In addition, more fluid-like substances were preserved in keratinocytes after bird's nest treatment under atomic force microscopy. In terms of upstream pathway regulation, bird's nest extract regulates the expression of filagramin molecules by mediating the phosphorylation of p38-MAPK and activating the expression of transcription factors GA-TA3, PPARα, PPARβ and PPARγ. The identification and analysis showed that N-acetylneuramic acid and 1.7 kDa small peptide had strong induction effect on filagglutinin-2 and filagglutinin-2 expression. In summary, although in vitro trials have shown that bird's nest may have multiple skin improvement effects, the results of clinical trials have revealed its limitations. At present, the active substances in bird's nest that promote skin health have not been accurately verified, but there is a consensus that they may be SA, mucin, active peptides and EGF-like active substances. Using anti-EGF antibodies combined with Westernblot analysis, the researchers did not detect EGF from bird's nest extracts, so the specific composition of the EGF-like active substance that promotes keratinization and fibroblast proliferation remains unknown. Suitable enzymolysis method can degrade the insoluble macromolecular glycoproteins to soluble small molecular peptides. It is found that the obtained peptides have specific biological activities and higher penetration and absorption potential. At present, most in vitro experiments and population experiments use the extracts of bird's nest, so the enzymatic method may be a means to discover new functional components of bird's nest in the future.

02 Regulation Dynamics

In 2016, the State Administration of Quality Supervision, Inspection and Quarantine issued an announcement to update the "Catalogue for the Implementation of the Registration of Overseas Producers of Imported Food" (hereinafter referred to as the "Catalogue for the Implementation of Registration"), and bird's nest products became the fourth category of food included in the "Catalogue for the implementation of Registration" after meat, aquatic products and dairy products. The registration of imported bird's nest overseas production enterprises has been implemented since January 1, 2016, including the production of edible bird's nest (refers to the bird's nest products made by sorting, soaking in water, cleaning, removing feathers, re-shaping, processing, drying, sorting and other processes, such as swallow cups, swallow strips, swallow cakes, swallow pieces, etc.) and bird's nest products (such as canned and bottled bird's nest products such as rock sugar bird's nest).

In 2021, the Fujian Provincial Market Supervision Bureau studied and formulated the "Fujian Province Non-ready-to-eat Bird's Nest Production License Review Rules (Trial)", in Fujian Province with hair or net bird's nest as raw materials, processed into bird's nest, bird's nest, bird's nest, bird's horn, frozen bird's nest and other non-ready-to-eat bird's nest producers, should be in accordance with the requirements, obtain food production license qualification.

03 Market application and product dynamics

Due to the improvement of consumers' living standards and the change of consumption concepts, in the context of the overall weak consumption in 2023, the online health products (health food, tonics, dietary nutritional supplements) market increased by 32.3% year-on-year. In 2023, the bird's nest market also achieved 10 consecutive years of growth. According to Cicada mother data, the sales heat of Tiktok 2023H1 nourishing health care increased by 103.6%, and traditional nourishing nutrition increased by 87.9%. In the rankings of traditional nourishing nutrition categories on Tmall in 2023, bird's nest only ranked second among medicinal and food homologous foods, far exceeding other nourishing nutrition categories. In the mainstream e-commerce platform for bird's nest sales (Tmall + Taobao + Douyin + Jingdong), the sales volume of bird's nest products in 2023 reached 9.625 million, an increase of 27%.

As an important part of the high-end health food market, bird's nest still has great potential for development. Its product types are diverse, such as canned ready-to-eat, drinks, lozenges and so on. Pregnant (male and female), pregnancy, postpartum, infants, school-age children, young people, office workers, middle-aged and elderly people are widely used. Bird's nest can be served hot or cold for dessert, or with mushrooms, flower glue, scallops to make a salty stew. There are also baked bird's nest egg tarts on the market, such as Dragon Boat Festival bird's nest zongzi, Mid-Autumn Festival bird's nest moon cake, Spring Festival bird's nest gift package. The delicious bird's nest porridge and the mixed flavor of the Chong bird's nest also have a certain consumer group. The improvement of the bird's nest industry chain and the deepening of marketing will also promote the development of the bird's nest market. In the future, the development potential of the bird's nest market will be gradually released, bringing more business opportunities and development space for participants in all links of the industrial chain.

04 Production technology status

Bird's nest contains a variety of proteins and carbohydrates, the protein is mainly in the form of glycoprotein, and the glycoprotein is mainly in the form of mucin, and sialic acid is its main sugar group. It is difficult to degrade natural mucin by enzymatic method. With the increase of age, the protease secreted by the human body gradually decreases, and it is difficult to digest and the protein bioavailability is not high after human intake of protein. Therefore, the technology of preparing oligopeptide from bird's nest by in vitro degradation has attracted wide attention. Some studies have disclosed the production method and filtration structure of a bird's nest peptide product, including raw materials, denaturation, primary enzymolysis, primary fire extinguishing, secondary enzymolysis, tertiary enzymolysis, secondary inactivation, filtration and impurity removal, concentration, sterilization, drying and other steps. Although the technology can improve the edible property of bird's nest, the molecular weight of the prepared bird's nest peptide product is 4.18×103 Mn and 1.37×104 Mw, which is not conducive to human digestion, absorption, utilization and absorption of effective components. The bird's nest is soaked in water, dried, crushed, sifted through 100-230 mesh powder, broken through the wall machine to obtain fine powder, the fine powder and deionized water are added to the mixer for mixing, and the resulting mixture is put into the sterilization box for sterilization. The compound gradient enzymolysis of xylanase, pectinase and papain was used for enzymolysis of protein by papain. Some of the methods for preparing peptide products of bird's nest by the above prior art have complicated steps, large equipment investment, and some simple steps, which only rely on the action of enzymes to decompose proteins, and the molecular weight and activity of the peptides obtained can not be guaranteed. At the same time, although the peptide products of bird's nest prepared by these processes are mostly aimed at breaking down the protein in bird's nest into small molecule peptides that are easily absorbed, so as to improve the edible and bioavailability of bird's nest, their actual medicinal or health care effects are not exact, and the existence of anti-fatigue peptides is ignored, so it is difficult to promote the actual use.

05 Introduction of scientists' technical achievements

The technology provides a simple process and high activity preparation method of bird's nest peptide with significant anti-fatigue effect. The invention discloses a processing method for high-activity bird's nest anti-fatigue peptide, which comprises raw material pretreatment, dynamic high-pressure microjet treatment, pulsed electric field assisted enzyme membrane coupling treatment, chitosan - nano iron treatment, vacuum concentration - vacuum microwave intermittent drying treatment. The bird's nest was pre-treated by dynamic high-pressure microjet technology, and the heat sensitive and active substances in bird's nest tissue were not damaged by high-speed collision and air pocket action. The swelling of bird's nest in water and the dissolution of water-soluble protein in water were ensured by homogenizing the feed liquid. The advanced spatial structure of bird's nest proteins is no longer tightly cross-linked by pulsing electric field technology, which greatly reduces the difficulty of protein separation caused by the presence of proteins in bird's nest in the form of mucins, thereby improving the efficiency of enzymolysis reaction, and avoiding the destruction of other active components in bird's nest with appropriate electric field intensity and mild processing temperature. Suitable membrane components were selected to build the enzyme-membrane coupling system, optimize the conditions of enzymolysis and separation, efficiently and accurately control the molecular weight of the enzymolysis product bird's nest anti-fatigue peptide, reduce the inhibition effect of enzymatic reaction products, improve the recycling efficiency of enzymes, and be suitable for continuous production. By forming a stable inclusion compound with chitosan iron nanoparticles, the complex spatial structure with more stable activity was obtained. In addition, the bitter taste of the anti-fatigue peptide was effectively reduced after enzymolysis due to pH adjustment by chemical reagents. The effect of temperature on the structure and physicochemical properties of the active peptide was greatly reduced, and the activity of the anti-fatigue peptide in bird's nest was better maintained. The above processing method can not only produce the anti-fatigue peptide of bird's nest, but also maintain the activity of the anti-fatigue peptide of bird's nest to the maximum extent. The obtained product has high nutritional value and good taste, which provides a new way for the development of anti-fatigue active peptide products of bird's nest.

06 Conclusion

Bird's nest is rich in substance, glycoprotein, active peptide, SA and other active ingredients have certain benefits to the skin health and immune function of ordinary women. For pregnant women, parturients and menopausal women in special physiological periods, SA, EGF and estrogen-like active ingredients in bird's nest play a certain regulatory role, which is suitable for a wide range of people. However, a large number of studies are still in the preliminary stage of validating or evaluating the efficacy of bird's nest. The basis of active substances and molecular biological mechanisms still need to be further clarified, such as the relationship between the regulation of intestinal flora and the role of intestinal mucosal barrier and immune promotion, the specific components of EGF-like and estrogen-like active substances in bird's nest and their absorption and metabolism processes. Or the regulatory targets of endogenous estrogen synthesis pathway by ingestion of bird's nest.

*Content Source: "A method for processing high-activity bird's Nest anti-fatigue peptide"

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