Views: 1 Author: Natalia Nowacka-Jechalke,Renata Nowak ,Marta Kinga Lemieszek ,Wojciech Rzeski ,Urszula Gawlik-Dziki ,Nikola Szpakowska and Zbigniew Kaczyński Publish Time: 2022-06-07 Origin: Nutrients 2021, 13, 161.
Polysaccharides are macromolecules that are abundant in fungal cell walls. Due to their extensive structural variation, they have the potential to be biological response modifiers (BRMs). The composition of monosaccharide residues, including their sequence and position, as well as their linkages and positions of glycosidic bonds, affects the activity of polysaccharides. Chitin is one of mushroom polysaccharides, which is a water-insoluble and indigestible compound that acts as a dietary fiber in the human gastrointestinal tract. Correspondingly, most of the polysaccharides present in mushrooms are water-soluble glucans with different types of glycosidic bonds, such as (1→3)-α-glucans and (1→3), (1→6)-β-glucans Dextran.
Mushrooms are an inexpensive and abundant source of glucans with health-promoting potential. Today, with the growing number of health-conscious consumers, the global beta-glucan market is expected to grow substantially, with a value of over $1 billion in 2020, according to the latest data. Mushroom polysaccharides, especially glucans, are known to exert anticancer activity through their immunostimulatory potential, including activation of the innate immune system and acceleration of host defense mechanisms. In addition to the anticancer potential, mushroom polysaccharides have a wide range of biological activities, such as antibacterial, antiviral, antioxidant, anti-inflammatory, etc. In Asian countries, the main glucan isolated from fungi used to treat cancer is beta-glucan.
Colon cancer is thought to be preventable by using natural chemopreventive agents. Due to its pleiotropic activity, mushroom polysaccharides are able to function at different steps of the carcinogenesis process, with the overall goal of reducing the incidence of cancer. In addition, some research results based on mushroom β-glucan have shown that mushroom polysaccharide can not only inhibit tumor growth, but also induce its synergistic effect with chemotherapeutic drugs or other immune stimulants. One innovative approach is to hypothesize that beta-glucan could be used to deliver chemotherapeutic drug-containing nanoparticles to the site of colon cancer to enhance its therapeutic effect.
Sparassis crispa, known as cauliflower mushroom in English, Hanabiratake in Japanese, and Ggoksongee (meaning blossom) in Korean, is an edible and medicinal mushroom that grows in temperate regions of Europe and North America. It is also a very popular cultivar in Asian countries, especially in Japan. Still, so far, Hydrangea has not been precisely defined and studied.
The aim of this study was to evaluate the content of α-glucan and β-glucan in crude polysaccharide (CPS) of Emidiococcus spp. collected from the natural environment in Poland, and to determine their chemical composition and structure. In addition, the chemopreventive effects of CPS on colon cancer were investigated by in vitro antitumor, anti-inflammatory and antioxidant activities.
The fruiting bodies of Hydrangea spp. contain approximately 13.4 grams of protein, 21.5 grams of carbohydrates, and 2.0 grams of fat per 100 grams of dry weight. Only trace amounts of proteins and phenols are ultimately present in CPS. The main compounds in crude polysaccharides were sugars, which were identified as glucose, galactose, mannose and trehalose by gas chromatography-mass spectrometry. 1H NMR spectrum confirmed the presence of β-glucan. A previous structural study of a polysaccharide isolated from Emidiococcus also indicated the presence of glucan, a β-(1-3)-D-glucan backbone with a β-(1 -6)-D-glucose side branch unit. The antitumor activity of Embroidered β-glucan has been previously studied alone or in combination with some chemotherapeutic agents, but there is no information on the chemopreventive properties of Embroidered polysaccharide components against colon cancer. Therefore, the anti-proliferative activity and cytotoxicity of the crude polysaccharide of wild embroidery were tested. In this study, the human colon epithelial cell line CCD841 CoN and three different human colon adenocarcinoma cell lines, which represent successive stages of colon cancer development according to the Dukes classification (Caco-2 cells: Dukes stage B, LS180 cells: Dukes Phase B, HT-29 cells: Dukes Phase C). Studies have shown that the crude polysaccharide isolated from wild Embroidered coccus has good in vitro biological activity. They were found to be nontoxic to normal human colonic epithelial cells while significantly inhibiting the proliferation of human colon cancer cells and disrupting the integrity of their cell membranes. It should be emphasized that CPS was the least efficient at clearing Caco-2 cancer cells, which is the most differentiated but least invasive cell line among the cells studied. In contrast, HT-29 cells, which represent the advanced stages of colon cancer development, were most sensitive to the anticancer effects of CPS. The anticancer activity of CPS was positively correlated with the invasive and undifferentiated properties of colon cancer. Embroidered polysaccharide has good activity in colon cancer cells with strong anti-destructive ability. Clearly, this observation deserves further validation in studies in in vivo models.
Inflammation is a host response to infection or tissue damage that occurs in a complex set of interactions between soluble factors and cells. Under normal circumstances, the inflammatory response is self-limiting. However, there is a strong relationship between long-term inflammation and the development of colon cancer. Colitis-associated cancer (CAC) is a subtype of colorectal cancer associated with inflammatory bowel disease (IBD). Chronic inflammation of CAC can lead to oxidative damage to DNA, resulting in p53 gene mutations observed in tumor cells and in inflammatory but non-dysplastic epithelial cells. Numerous studies have shown that mushroom polysaccharides, including beta-glucans, have immunomodulatory or anti-inflammatory activities. Inducible cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) are inflammatory biomarkers produced by the body. Previous studies have shown that the non-aqueous fraction of hydrangea extract inhibits prostaglandin E2 (PGE2) production by downregulating COX-2 expression. This study demonstrates the anti-inflammatory potential of CPS in directly inhibiting pro-inflammatory enzymes such as COX-2 and LOX. Whether there are other mechanisms for the anti-inflammatory activity of hydrangea polysaccharides remains to be further investigated. Excessive production of reactive oxygen species (ROS) in humans leads to oxidative stress that contributes to a variety of pathological conditions, including the development of colon cancer. It occurs through a high susceptibility to the effects of pro-oxidative and toxic factors, with concomitant increases in cancer cell proliferation. Studies have shown that CPS has moderate anti-radical activity, strong reducing and chelating activities, and a high potential to inhibit lipid peroxidation. CPS can also inhibit the lipid peroxidation of linoleic acid peroxidation on hemoglobin. In addition, the ORAC experiment using AAPH-derived peroxyl radicals to mimic lipid peroxyl radicals was involved in the lipid peroxidation chain reaction in vivo, confirming the antioxidant properties of hydrangea polysaccharides. The antioxidant activity of natural crude polysaccharides may be attributed to various compounds present in mushroom extracts, such as phenolic compounds. The current study showed that crude polysaccharides also exhibited moderate or even high antioxidant potential, independent of total phenolic content. Antioxidant properties may be particularly related to the presence of beta-glucan in the mushroom polysaccharide fraction. Of course, the relationship of functional structure needs further study. This study also used a catalase assay to measure antioxidant activity. Catalase protects cells from oxidative stress by breaking down hydrogen peroxide into water and oxygen. Therefore, promoting catalase activity is one of the indirect mechanisms of antioxidant activity and is beneficial from the perspective of normal cell physiology. On the other hand, studies have shown that catalase helps increase the resistance of cancer cells to pro-oxidant drugs (especially in H2O2-mediated processes). Inhibition of catalase expression and activity results in increased oxidative stress in cancer cells. Therefore, the search for catalase inhibitors to design synergists of anticancer drugs may help to sensitize drug-resistant cancer cells. The present study shows that hydrangea polysaccharides inhibit catalase activity, so they appear suitable for application in enhancing anticancer chemotherapy.
Taken together, CPS has broad chemopreventive potential based on several different mechanisms of action. In vitro studies showed that CPS significantly inhibited colon cancer cell proliferation without detrimental effects on normal cells, and the antioxidant and anti-inflammatory activities were consistent with colon cancer prevention strategies. Since colon cancer is related to human food and lifestyle, it is crucial to find natural chemopreventive agents in the daily diet. CPS can be added to the human diet as a nutraceutical or functional food ingredient. The fruiting bodies of Hydrangea can also be used as part of the daily diet. The potential application of the chemical structure of hydrangea polysaccharides in colon cancer prevention and treatment will be addressed in further studies.
