Advances in Medical Research of Glucosamine

2020-08-17 14:10KangLIJunqingWANGXuLIZhaoWENSongsenSUIJianbinWANGChuanzhuangGUOPiwuLI
农业生物技术(英文版) 2020年3期

Kang LI Junqing WANG Xu LI Zhao WEN Songsen SUI Jianbin WANG Chuanzhuang GUO Piwu LI

Abstract Glucosamine, referred to as GlcN, is a product in which one hydroxyl group of glucose is replaced by one amino group. GlcN is widely present in plants, animals and microorganisms. After research, ammonia sugar has a good effect on the treatment of osteoarthritis, the suppression of cancer, and the recovery of cognitive impairment caused by hypoxia in some animals. This article summarized the application of GlcN in the medical field, and lays a foundation for the further development of GlcN in the field of biomedicine.

Key words Glucosamine; Osteoarthritis; Cancer; Biomedicine

Received: January 29, 2020Accepted: March 20, 2020

Supported by the National Science Foundation of China (31801527); Focus on Research and Development Plan in Shandong Province (2019JZZY011003, 2018YFJH0401, 2016CYJS07A01); Taishan Industry Leading Talent (tscy20180103) ; Shandong Provincial Natural Science Foundation (ZR2016CB04); Major Program of National Natural Science Foundation of Shandong Province (ZR2017ZB0208); Cultivation Project of Shandong Synthetic Biotechnology Innovation Center (sdsynbio-2018-PY-02).

Kang LI (1994-), male, P. R. China, devoted to research about microbial enzyme technology.

Corresponding author. E-mail: piwuli@126.com.

N-acetylglucosamine is the product of acetylation of glucosamine. It is widely present in plants, animals and microorganisms[1-4]. In cells, a variety of structural macromolecular substances produced by amino sugars as precursor molecules, such as peptidoglycan and lipopolysaccharide in bacteria, chitin in insects and fungi, they are the important components of bacterial and fungal cell walls[5-8]. In addition, GlcN is also an essential component of mucosal secretions, connective tissue, skin, tendons, ligaments and cartilage[9-11].

Application of Glucosamine in the Treatment of Arthritis

In 2006, researchers explored GlcN餾 theory of delaying joint failure. Experiments have shown that glucosamine sulfate can not only inhibit MMP-2 secretion in cartilage, meniscal and synovial cultures, but also reduce MMP-9 production in synovial and meniscal cultures. One of the effects of glucosamine sulfate on joint failure is to regulate urokinase PA (u-PA), PA inhibitor 1 (PAI-1) and gelatinase (matrix metalloproteinase 2 and -9[MMP-2 and -9]), thereby delaying joint failure[12].

Nagaoka et al. [13] studied the effects of glucosamine on endothelial cells and intestinal epithelial cells in 2011. The results showed that glucosamine can not only act as a cartilage protectant, but also as an anti-inflammatory molecule in the body. Yang et al.  [14] studied the selective inhibitory effect of N, N, N-trimethyl-d-glucosamine-chitooligosaccharide as a glycosyl hydrolase family 20 β-N-acetyl-d-hexosidase in 2011. The selectivity of agents is also beneficial for disease control and plant protection.

Glucosamine Has Inhibitory Effects on Cancer and Tumors

Ju et al. [15] studied the effect of glucosamine on lung cancer cell proliferation, and evaluated cyclin E in key cyclins in the G1/S transition and ubiquitin ligase subunit Skp2, which targets the negative cell cycle regulator p27Kip1 expression. In addition, the potential mechanism of action of glucosamine in lung cancer cells was studied. It was found that glucosamine can block lung cancer cells at the G1/S phase, therefore, glucosamine can prevent G1/S by inhibiting the expression of cyclin E and Skp2 proteins S transition, thereby inhibiting the proliferation of lung cancer cells. In 2016, Pohlig et al. [16] investigated the underlying mechanism of GlcN餾 anti-sarcoma effect, and found that glucosamine sulfate significantly inhibited MMP-3 and MMP-9 mRNA and protein levels in vitro osteosarcoma cell lines, which further illustrates the potential antitumor efficacy of glucosamine sulfate in osteosarcoma.

Application of Glucosamine in the Treatment of Neurodegenerative Diseases

In 2018, Lee et al. [17] observed adult zebrafish caused their own neuritis and reduce their cognitive ability in the state of acute hypoxia. They measured the zebrafish餾 athletic ability and exploration activities in a hypoxic environment after pretreatment with GlcN and assessed motor neuron defects, finding that neurons could recover quickly. It fully demonstrates that the neuroinflammation and learning and memory impairment of adult zebrafish caused by hypoxia are inhibited by glucosamine. In 2016, Park et al.  [18] studied the effect of GlcN on platelet activating factor PAF-induced cell activation in human HMO6 microglia. The data indicate that GlcN may have important potential for the treatment of inflammatory and neurodegenerative diseases with microglia activation [18].

Harm of oral glucosamine to human body

As we all know, hepatitis B virus (HBV) replication and envelope are accomplished by autophagy. In 2019, Liu et al. [19] conducted in vitro and in vivo experiments to verify whether and how GlcN affects HBV replication. The results showed that GlcN also promoted in vitro replication of influenza A virus, enterovirus and vesicular stomatitis virus. In summary, GlcN effectively promotes virus replication by inhibiting the dual effects of autophagy degradation and MTORC1 signal transduction, and by inducing autophagy stress. Therefore, in patients with chronic viral infections, oral GlcN intake has the potential risk of enhancing viral replication.

In 2016, Moore et al. [20] assessed the effect of GlcN on insulin action in cultured retinal Müller cells. GlcN promotes endoplasmic reticulum stress in retinal cells, which leads to increased DNA damage and increased expression of proteins regulated during development, leading to insulin resistance. Oral GlcN can cause insulin resistance and elevated plasma glucose levels[11], which is of great significance for the development of human health.

Discussion

Glucosamine has become more and more important in human life, and its important role in the treatment of lung cancer and the remarkable properties of fighting tumors have opened a new door in the field of biomedicine. Because of its important position in the body, glucosamine is also widely used in the food industry and cosmetics industry.

References

[1] CHEN JK, SHEN CR, YEH CH, et al. N-acetyl glucosamine obtained from chitin by chitin degrading factors in Chitinbacter tainanesis[J]. Int J Mol Sci, 2011, 12(2): 1187-1195.

[2] KAPOOR M, MINEAU F, FAHMI H, et al. Glucosamine sulfate reduces prostaglandin E(2) production in osteoarthritic chondrocytes through inhibition of microsomal PGE synthase-1[J]. The Journal of Rheumatology, 2012, 39(3): 635-644.

[3] NAGAOKA I, IGARASHI M, SAKAMOTO K. Biological activities of glucosamine and its related substances[J]. Advances in Food and Nutrition Research, 2012(65): 337-352.

[4] YADAV V, PANILAITIS B, SHI H, et al. N-acetylglucosamine 6-phosphate deacetylase (nagA) is required for N-acetyl glucosamine assimilation in Gluconacetobacter xylinus[J]. PLoS One, 2011, 6(6): e18099.

[5] ROGACKA D, PIWKOWSKA A, JANKOWSKI M, et al. Expression of GFAT1 and OGT in podocytes: transport of glucosamine and the implications for glucose uptake into these cells[J]. Journal of cellular physiology, 2010, 225(2): 577-584.

[6] KIM CH, CHEONG KA, PARK CD, et al. Glucosamine improved atopic dermatitis-like skin lesions in NC/Nga mice by inhibition of Th2 cell development[J]. Scandinavian journal of immunology, 2011, 73(6): 536-545.

[7] HULIKOVA K, SVOBODA J, BENSON V, et al. N-acetyl-D-glucosamine-coated polyamidoamine dendrimer promotes tumor-specific B cell responses via natural killer cell activation[J]. International immunopharmacology, 2011, 11(8): 955-961.

[8] HIRANO T, AOKI M, KADOKURA K, et al. Heterodisaccharide 4-O-(N-acetyl-beta-D-glucosaminyl)-D-glucosamine is an effective chemotactic attractant for Vibrio bacteria that produce chitin oligosaccharide deacetylase[J]. Letters in applied microbiology, 2011, 53(2): 161-166.

[9] APOSTU D, LUCACIU O, MESTER A, et al. Systemic drugs with impact on osteoarthritis[J]. Drug Metab Rev, 2019, 51(4): 1-26.

[10] YAMAGISHI Y, SOMEYA A, IMAI K, et al. Evaluation of the anti-inflammatory actions of various functional food materials including glucosamine on synovial cells[J]. Mol Med Rep, 2017, 16(2): 1353-1359.

[11] GUO Q, HU HL, ZHOU Y, et al. Glucosamine induces increased musclin gene expression through endoplasmic reticulum stress-induced unfolding protein response signaling pathways in mouse skeletal muscle cells[J]. Food and Chemical Toxicology, 2019, 125: 95-105.

[12] CHU SC, YANG SF, LUE KH, et al. Glucosamine sulfate suppresses the expressions of urokinase plasminogen activator and inhibitor and gelatinases during the early stage of osteoarthritis[J]. Clinica Chimica Acta, 2006, 372(1): 167-172.

[13] NAGAOKA I, IGARASHI M, HUA J, et al. Recent aspects of the anti-inflammatory actions of glucosamine[J]. Carbohydrate Polymers, 2011, 84(2): 825-830.

[14] YANG Y, LIU T, YANG YL, et al. Synthesis, evaluation, and mechanism of N,N,N-trimethyl-D-glucosamine-(1-->4)-chitooligosaccharides as selective inhibitors of glycosyl hydrolase family 20 beta-N-acetyl-D-hexosaminidases[J]. Chembiochem: A European Journal of Chemical Biology, 2011, 12(3): 457-467.

[15] JU YH, YU AM, SUN XH, et al. Glucosamine, a naturally occurring amino monosaccharide, inhibits A549 and H446 cell proliferation by blocking G1/S transition[J]. Molecular medicine reports, 2013, 8(3): 794-798.

[16] POHLIG F, ULRICH J, LENZE U, et al. Glucosamine sulfate suppresses the expression of matrix metalloproteinase-3 in osteosarcoma cells in vitro[J]. BMC Complementary and Alternative Medicine, 2016, 16(1): 313.

[17] LEE Y, LEE S, PARK JW, et al. Hypoxia-induced neuroinflammation and learning–memory impairments in adult zebrafish are suppressed by glucosamine[J]. Molecular Neurobiology, 2018, 55(11): 8738-8753.

[18] PARK JH, KIM JN, JANG BC, et al. Glucosamine suppresses platelet-activating factor-induced activation of microglia through inhibition of store-operated calcium influx[J]. Environmental Toxicology and Pharmacology, 2016(42): 1-8.

[19] LIU Y, WU CC, WANG XY, et al. Glucosamine Promotes Hepatitis B Virus Replication Through its Dual Effects in Suppressing Autophagic Degradation and Inhibiting MTORC1 Signaling[J]. Autophagy, 2019, 16(3): 548-561.

[20] MOORE JA, MILLER WP, DENNIS MD. Glucosamine induces REDD1 to suppress insulin action in retinal Müller cells[J]. Cellular Signalling, 2016, 28(5): 384-390.

Editor: Yingzhi GUANGProofreader: Xinxiu ZHU