"Food Science" Expert Abstract: Advances in research on physiological functions and its mechanism of hyaluronic acid

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"Food Science" Expert Abstract: Advances in research on physiological functions and its mechanism of hyaluronic acid

2022-01-15 12:07:42 8 ℃

Hyaluronic acid (HA) (Figure 1), commonly known as hyaluronic acid, earliest from the University of Colombian University, MEYER and Plamer from the bullocyte vitreous. In nature, HA is widely present in various tissues of animals, such as closed cavity, blood vessels, heart, eye, brain and skin, etc., which are passed by D-glucuronic acid (GLCA) and N-acetyl glucamine (GLCNAc). The -1,3 glycosidism is coupled to form a double sugar unit structure, and then a linear non-sulfurized glycosamin is attached by β-1,4-glycosidic bonds.

HA has a wide range of applications in ophthalmology, orthopedics, skin, plastic surgery, endoscopy, burn and other fields. However, compared with other countries, the R & D and clinical use of HA products in my country are still limited. In overseas markets, food grade HA raw materials have been widely used in various food and beverages and health products. On January 7, 2021, the National Health and Health Committee (hereinafter referred to as Qijian Committee) issued, approved sodium hyaluronate (ie hyaluronic acid) as "new food raw materials", can be applied to ordinary food added.

Xukang, the School of Pharmacy, Tsinghua University, and Xukang, the basic medical school of Capital Medical University, have reviewed the currently published HA-related representative research results, mainly paying attention to the absorption, distribution and metabolic pathways in the body, and HA for HA The effect of different organizations, organs, and combined with pharmacology, toxicology research on the development and application of oral HA products, while improving the validity of the public for oral HA.

1, the absorption and metabolism of HA is given

Studies have shown that 80% of MMW-HA (900 kDa) stems from chicken comb cells can be absorbed by the body, and the subsequent portion HA is operated to the skin, joints, etc. In the oral administration experiment of the radiolabeled HMW-HA, about 90% of HA can be detected in the body, mainly concentrated in feces. Experimental results were carried out using CaCO-2 cells (human cloned coli gland cancer cells, structural and function similar to differentiated small intestinal epithelial cells) showed that HA of molecular mass is more than 100 kDa is difficult to absorb directly by the cell, and molecular mass is not more than 70 kDa. HA can penetrate into the intestinal epithelial cell, and the lower molecular mass HA (≤5 kDa) can also be intracellular in the cells by passive diffusion. Further, the absorption effect administered with the HA has correlation with the relative molecular mass, and it is speculated that one or more protein (HA receptors) mediates absorption of HA, and the affinity of the protein and the HA has a relative molecular mass correlation. The above results suggest that depending on the molecular mass of the molecular mass, the absorption site, absorption method, and the pathway to the blood circulation after the HA are different, and HA-mediated transportation is to be analyzed.

After HA is administered to the mouth, the retention time in the body is: the stomach 2 h, the small intestine 4 h, and the cascadus 24 h (Fig. 2). The results of human gastric juice and artificial intestinal fluid showed that HA would not be degraded by enzymes in the artificial gastric liquid or human sausage liquid, but in turn, it is possible to degrade into oligosaccharides in the cities of the cities, and is mainly dilasted.

2, the effect of oral administration to HA on the health of the skin

HA in the skin was synthesized from HAS in epidermal keratinocytes and leather fibroblasts, wherein the HA content in the leather was higher than the epidermis. Among the leather, HA adjusts water balance and maintaining cellular structures through its high-quality and viscous. External HA can enhance skin natural defense function, accelerate wound healing; improve skin physiological characteristics, improve skin firming, relieve skin inflammation and wrinkles; stimulate leather layer fibroblasts, and promote collagen synthesis. In recent years, as a method of facial anti-aging wrinkles, local HA filler has been widely used in medical beauty surgery. HA is injected into the leather layer to improve facial wrinkles for a long time and enhance facial soft tissue, and more side effects compared to collagen. Small, better tolerance.

3, the effect of HA on the joint

The HA can effectively prevent and treat mice bone jointitis, reduce the symptoms of joint redness, improve serum indicators, including tumor necrosis factor-α (TNF-α), interleukin (IL) -1, MDA and SOD levels, etc. And the amino glucose is evolved after oral HA adjuvant. Related studies show that oral HA can effectively reduce the pain of knee arthritis; random, double blind, placebo control experiments in 2008-2015 show that oral HA can be used to treat synovitis related symptoms, relieve knee pain, slide Membrane effusion and inflammation, improve knee strength, etc. After 8 consecutive years of oral HA, the pain of patients with joint pain and the stiffness have a significant relief. After taking the HA-rich chicken extract, the knee oa is extracted, and the pain is significantly reduced, and it is also able to inhibit the player's cartilage degradation and promote bone resistance; HA of molecular mass is 900 kDa can effectively treat knee osteoarthritis; knee pain After 3 months, the patient has orally orally, the muscle function is improved, the synovial fluid is reduced and the pain is reduced; oral HMW-HA (2 500 ~ 2800 kDa) can also reduce chronic joint pain. Oral HA is more compliant with injection HA, and more side effects are smaller and economical, and has a broader application prospects and development potential.

4, the effect of HA for intestinal health is based on HA-based nanoparticle drugs with high safety, small side effects, and good effects are gradually replacing traditional treatment drugs for IBD. HA-bilirubin nano drug (HABN) can target intestinal barrier function, flora, steady state, and immune response to regulating colitis model mice. On the one hand, HA itself has immunomodulatory properties to activate macrophages, dendritic cells, and regulatory T cells (Regulatory T cell, Treg cells) and reduce the number of neutrophils and monocytes, inducing antibacterial peptide expression, Plays anti-inflammatory and repair the function of the intestinal barrier; on the other hand, the hydrophilic carrier is taken by HA, so that hydrophobic antioxidant drugs (e.g., bilirubin) can be used orally, absorbed into the cell. The results showed that HABN effectively inhibited colon tissue damage and immunocyte infiltration due to sodium dextran sulfate, and at the same time, the level of tight linins, occludin, ZO-1 in the intestinal tissue increased, and accephysia The expression level of factor and apoptosis factor is lowered. The 16S rRNA sequencing results show that HABN can significantly increase the diversity of intestinal flora and improve flora disorders, increase probiotics such as Akkermansia Muciniphila, Clostridium Xivα, Lactobacillus.

5. The effect of HA for the eye is given

Dry eye disease (DED) is a common chronic eye surface disease, which is characterized by tear film steady state disorders, mainly as tear film is unstable, high permeability, inflammation, and neurological feelings, which ultimately leads to an ineextile discomfort. The basic treatment of the DED mainly rely on the drop of lubricating eye drops or tackifiers. The HA is used as a macromolecularly viscous polysaccharide, which is widely distributed in connective tissue, epithelial tissue and neural tissue, which have been added to tear supplements for the treatment of DED, which acts as a partial agent to enhance lubrication, while also promoting cornea Healing of the upper skin wound.

Two options have been compared by using a local lubricant (control group) of 0.15% HA-shaped suspension (control group), and HA local slip agent (experimental group). Therapeutic effect on the DED. The effect of oral HA is evaluated with the number of oral HA for the treatment of DED with a tear surface disease index (OSDI). The results showed that the effect of oral and local HA combined with the DED was significantly better than the individual HA topical medication, suggesting that oral HA has a potential advantage of synergistic treatment of DED.

6. Safety research given to HA

In a double-blind human experiment, 12 consecutive months, more than 200 mg HA per day and 8 consecutive years, no side effects were shown in 240 mg HA per day; single dose toxic experiment results showed that HA is orally given Half monarch (LD 50) is 2 400, 800, 1 000 mg / kg, respectively, and long-term intake recommendation dose. Repeated dose toxicity results showed that 1 330 mg / kg continuous oral administration was given to 90 days and did not have toxic effect on rabbits. At the same time, the oral dose of 670 mg / kg does not cause reproduction and developmental toxicity to rats. As shown in Table 1, multiple studies have proven that oral HA has high safety.

7, junction

The HA is a structurally stable diose (D-GLCA and GLCNAc) unit linear chain glycosamine, and is widely present in the surface of the body cell and the intercellular matrix, with a variety of physiological functions, and participate in multiple organisms. Learning process. After the HA is administered, it is subjected to a fragment of the intestinal flora or enzymatic or enzyme as a size, and is transported to different sites (Fig. 3). As the age is growing, the HA level in the body is gradually lowered, and Oral HA is expected to supplement the HA of the body, thereby regulating the body-related function, promoting and maintaining the health of the body. At present, in vivo, in vitro experiments and patient double-blind experiments have initially proved that oral HA plays an important role in maintaining skin health, repair joint damage, regulating intestinal immunity, relieving dry eyes, etc .; at the same time, its safety is high, no It has immunogenic, non-allergen, no reproductive, developmental and genetic toxicity, and has no effect on cancer metastasis.

Wang Zhu Professor

Tsinghua University School of Pharmacy

Dr. Wang Yu, Ph.D. Professor Tsinghua University School of Pharmaceutical, Director of Ph.D., Department of Pharmacology, Double Professor Tsinghua University College of Life Sciences. Since China, we have obtained a bachelor's degree, a master's degree in medicine, a master's degree in pharmacy, and a Ph.D. in pharmacy. From 1996 to 1998, he was employed in the Department of Pharmacology, Japan, National Institute of Medicine, Department of Pharmacology, Department of Pharmacology, Department of Pharmacology. In 1998, as an introduction of talents from overseas, I was hired from overseas, and I was working on the Department of Life Science and Engineering, Tsinghua University (now College of Life Sciences). In 2003, they participated in the construction and joined Tsinghua University Medical College. Tsinghua University School of Pharmaceuticals work. During the Pediatric Department of Pediatrics, the Department of Genetics, the Harvard Medical School, the Genetic School of Harvard Medical College. Overseas special hierarchy of Japan's National Okayama University has been served. He has participated in the creation of many biomedical related companies, and listed companies in the pharmaceutical field, the board of directors, independent directors for many years. Professor Wang Zhao once served as assistant at the Dean of Tsinghua University Research Institute. He is also served as the Director of the Biological and Pharmaceutical Equipment Research Institute of Tianjin High-end Equipment Research Institute of Tsinghua University. The main research direction is the mechanism of aging biology and pharmacology, especially aging molecular cell pharmacology and drug intervention aging, as well as nerve and metabolic pharmacology and modern Chinese medicine modernization. Host (pass) major special projects, national key research and development plans, 973, 863, National Natural Science Foundation of China (including key projects), doctoral funds in the Ministry of Education, etc., published nearly 200 articles, including SCI collection papers More than 150. Professor undergraduate and graduate students, such as molecular biology, mechanism of apoptosis, biological pharmaceutical engineering, pharmacology, aging biology, etc. Special inspector of the Beijing Municipal People's Government. (Zeng), a Pharmazie Editor, SCIENTIFIC REPORTS Editor, Food Science And Human Wellness, Side Editor, Journal of Future Foods Editor, Deputy Editor, "Food Science" editor, etc., published Academic discussion / translation, such as Aging and Aging-Related Diseses: Mechanisms and Interventions, "Biological Separation: Research Methods and Experimental Program", "Aging Biology", "Longevity Password: Tips from Science Frontiers", etc. . Professor Wang Zhu has a broad field of view and deep attainments in aging, and has a broad vision and profound attainment, especially in the body and organs, brain aging / old-fashioned disorder (dementia), bone The aging / osteoporosis and senior metabolic disorders have in-depth research and published relevant scientific research papers, for more than ten years of responsible persons (aging drug intervention), and several times in international academics At the meeting, discussing the state's understanding and countermeasures for aging research at the top Xiangshan Science Conference, providing reference comments for national health and medical and pension.

Professor Wang Wei exclusive interview

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This paper "Physiological function and development of hyaluronic acid" is derived from "Food Science" in "Food Science" 2021 (Food Science "2021, 42, 23rd. JOURNAL OF PATHOPHYSIOLOGY. . Click on the original text to view the article.

Modify / edit: Yuan Yi; Responsible Editor: Zhang Ruimei

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