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Qi, L.;  Shi, Y.;  Li, C.;  Liu, J.;  Chong, S.;  Lim, K.;  Si, J.;  Han, Z.;  Chen, D. Glucomannan in Dendrobium catenatum. Encyclopedia. Available online: https://encyclopedia.pub/entry/34192 (accessed on 05 December 2023).
Qi L,  Shi Y,  Li C,  Liu J,  Chong S,  Lim K, et al. Glucomannan in Dendrobium catenatum. Encyclopedia. Available at: https://encyclopedia.pub/entry/34192. Accessed December 05, 2023.
Qi, Luyan, Yan Shi, Cong Li, Jingjing Liu, Sun-Li Chong, Kean-Jin Lim, Jinping Si, Zhigang Han, Donghong Chen. "Glucomannan in Dendrobium catenatum" Encyclopedia, https://encyclopedia.pub/entry/34192 (accessed December 05, 2023).
Qi, L.,  Shi, Y.,  Li, C.,  Liu, J.,  Chong, S.,  Lim, K.,  Si, J.,  Han, Z., & Chen, D.(2022, November 11). Glucomannan in Dendrobium catenatum. In Encyclopedia. https://encyclopedia.pub/entry/34192
Qi, Luyan, et al. "Glucomannan in Dendrobium catenatum." Encyclopedia. Web. 11 November, 2022.
Glucomannan in Dendrobium catenatum
Edit

Dendrobium catenatum is a classical and precious dual-use plant for both medicine and food in China. It was first recorded in Shen Nong’s Herbal Classic, and has the traditional functions of nourishing yin, antipyresis, tonifying the stomach, and promoting fluid production. The stem is its medicinal part and is rich in active polysaccharide glucomannan. As an excellent dietary fiber, glucomannan has been experimentally confirmed to be involved in anti-cancer, enhancing immunity, lowering blood sugar and blood lipids, etc.

Dendrobium catenatum glucomannan biosynthetic pathway

1. Feature and Structure of Glucomannan

Unlike other soluble fibers, glucomannan is characterized by high viscosity [1]. As a hemicellulose polysaccharide, glucomannan is ubiquitous in the plant cell wall. Moreover, glucomannan exists as energy storage substance in Araceae, Liliaceae, and Iridaceae and Orchidaceae [2]. It was reported that glucomannan contributes to plant tolerance to the lack of water as a compatible solute and the succulence in Aloe vera [3]. Storage glucomannans in distinct species display different structures. The mannose:glucose (Man:Glc)ratio is 1.6:1.0 in glucomannan from Amorphophallus konjac and 3.0:1.0 in glucomannan from Orchis mascula [4][5]. The Man:Glc ratios of three glucomannans (ASP-4N, ASP-6N and ASP-8N) in Aloe leaves are 19.13:1, 8.97:1, and 2.96:1, respectively [6]. In addition, glucomannan can also be obtained from microorganisms, such as the cell walls of bacteria, yeast, or fungus [7][8]. Natural glucomannan is composed of D-glucose and D-mannose linked by a β-1,4-glucopyranoside bond to form polymer heteropolysaccharides in a certain molar ratio [9]. Moreover, the C3 position of D-mannose on the main chain can be linked to polysaccharides in the form of β-1,3-glycosidic bond or β-1,6-glycosidic bond [10].
Glucomannan is the main polysaccharide active component in D. catenatum, and its derivatives also contain other monosaccharides, such as galacturonic acid, glucuronic acid, and galactose [11]. The contents of mannose and glucose in total polysaccharides from D. catenatum are 120.60 mg·g−1 and 71.23 mg·g−1, respectively [12]. Several glucomannans from D. catenatum have been reported to exhibit different Man:Glc molar ratios [13][14][15], and contain abundant O-acetyl groups [16][17][18]. Acetylation can increase the activity and health benefits of glucomannan [19].

2. Applications of Glucomannan

2.1. Medical Applications

D. catenatum has multiple traditional functions and has been developed into various medicines, such as Mailuoning injection (Jinling Pharmaceutical Co., Nanjing, China), Tongsaimai tablet (Jiangsu Kangyuan Sunshine Pharmaceutical Co., Nanjing, China), and Dendrobium nightlight pill (Tong Ren Tang, Beijing, China). Modern medicine has shown that D. catenatum polysaccharides have diverse bioactivities, including immunomodulatory, anti-tumor, gastro-protective, hypoglycemic, anti-inflammatory, hepatoprotective, and vasodilating effects [20]. In this entry, major emphasis will be placed on the gastrointestinal protection, immunomodulatory, anti-cancer, hypoglycemic, and hypolipidemic functions of D. catenatum glucomannan.

2.1.1. Intestinal Health Improvement

It has been reported that glucomannan can modulate mouse cecal and fecal microbiota with favorable prebiotic effects [21]. The unique properties of glucomannan hydrolysate make it valuable as a prebiotic in a wide range of food, feed, and pharmaceutical products [22]. Prebiotics promote specific changes in the gastrointestinal microbiota [23], promote the growth of probiotics such as Lactobacillus and Bifidobacterium, inhibit the proliferation of harmful bacteria, reduce inflammation, improve the integrity of the intestinal mucosa, promote nutrient absorption [24], and control the blood glucose level of patients with type 2 diabetes [25]. Glucomannan selectively stimulates the production of beneficial gut microflora such as probiotics and benefits the treatment of functional gastrointestinal disorders related to abdominal pain in mice [26][27][28]. The combined laxative of glucomannan-probiotic promotes defecation in constipated rats [29]. Mannose-oligosaccharides, the oxidative degradation product of glucomannan, are potential prebiotics, which can affect the growth and species abundance of fecal microbiota and regulate the balance of intestinal flora [30][31]. For instance, D. catenatum polysaccharide DOP can restore the diversity of intestinal flora and regulate the abundance of intestinal flora by inhibiting the overexpression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), restoring the level of short-chain fatty acids (SCFAs), activating G-protein-coupled receptors (GPRs), and regulating the intestinal flora to alleviate the symptoms of colitis in mice [32].
Glucomannan also plays a direct role in protecting the intestinal epithelium. D. catenatum polysaccharide DOP is not easily digested and absorbed in the human body but is degraded into SCFAs by the gut microbiota in the large intestine, therefore improving intestinal health [12][33]. In addition, D. catenatum glucomannan can reduce intestinal epithelial injury and regulate intestinal mucosal immunity by keeping a balanced ratio of pro- and anti-inflammatory cytokines and regulating the expressions of toll-like receptors (i.e., TLR-2, TLR-4, TLR-6, and TLR-9) important for recognizing pathogen-associated molecular patterns derived from various microbes in mice [34].

2.1.2. Immunomodulatory Activity

Glucomannan, one of the natural bioactive ingredients, can be used as an ideal immunomodulatory agent. Glucomannan can reduce brain inflammation, improve hippocampal neuron damage, maintain hippocampal cognitive function, and play an anti-epileptic role in epileptic rats [35]. D. catenatum polysaccharide DOPW3-B can improve the intestinal mucosal immune activity by increasing at Peyer’s patches the levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4), two key effector cytokines for the differentiation of T helper types 1 and 2 with a positive effect on mesenteric lymph nodes [36][37]. Glucomannan can increase the expression of several cytokines that are important for immune homeostasis (e.g., TNF-α, IL-β and IL-10) [38]. Meanwhile, glucomannan plays a pivotal role in regulating the activation and proliferation of macrophages [39], and promoting phagocytosis [40]. Finally, the pretreatment of D. officinale with organic solvents enhances the immunostimulatory activity of polysaccharides and affects the mannose/glucose ratio of polysaccharides, which plays an important role in immunostimulation [41].

2.1.3. Anti-Cancer Activity

In a zebrafish xenograft model, D. catenatum polysaccharide DopW-1 inhibits the proliferation of HT-29 cells by the apoptosis pathway and has an anti-tumor effect on colorectal cancer [42]. It is known that hyper-activation of the phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signaling pathway in human cancers can promote the proliferation and survival of tumor cells [43]. Glucomannan can block the PI3K/AKT pathway, thereby promoting the apoptotic rate and reducing the proliferation ability of tumor cells [44]. In parallel, glucomannan can also inhibit the expression of major chemokine receptors, chemokine receptor 4 (CXCR4) and CC chemokine receptor 7 (CCR7), found in a wide range of tumor cells, thus reducing the dissemination ability of tumor cells [45]. In addition to directly interfering with tumor cells, glucomannan also acts in an indirect manner. The D. catenatum polysaccharide DOPa-3 significantly inhibits the formation and growth of colon tumors and alleviates colon injuries [46]. In rats, DOPA-4 effectively inhibits precancerous lesions of gastric cancer induced by 150μg/mL MNNG [47]. D. catenatum polysaccharides can reduce oxidative stress level, inhibit stress-induced activation of adenosine monophosphate-activated protein kinase (AMPK)/UNC-51 like autophagy activating kinase 1 (ULK1) pathway and the expression of light chain 3 (LC3) I and LC3 II proteins, reduce Beclin1 expression, and then reduce hypoxia/reoxygenation induced astrocyte autophagy, reduce human astrocyte apoptosis, and promote astrocyte survival [48].

2.1.4. Hypoglycemic Activity

Glucomannan is suitable as a dietary fiber supplement for the treatment of being overweight, hyperlipidemia, and diabetes. D. catenatum glucomannan DOP can alleviate hyperglycemia in high fat diet (HFD)/streptozocin (STZ)-induced diabetic mice through promoting the synthesis of liver glycogen and inhibiting the degradation of liver glycogen [49].
DOP treatment can reduce the level of bile acid in diabetic rats, reduce the binding of bile acid to the nuclear receptor FXR or the membrane receptor TGR5, increase the level of glucagon-like peptide-1 (GLP-1), and improve glucose and lipid metabolism and insulin sensitivity [50]. DOP promotes glycogen synthesis by regulating the expression of glycogen synthase kinase 3β (GSK-3β) and glycogen synthase (GS) in the liver or glucose transporter 4 (GLUT4) in muscle. Glucose levels are reduced by regulating the activity of glucose metabolism enzymes in the liver, including pyruvate kinase (PK), hexokinase (HK), and phosphoenolpyruvate carboxykinase (PEPCK) [51]. On the other hand, DOP can delay diabetic cataract by decreasing the level of serum malondialdehyde (MDA), increasing the activity of superoxide dismutase (SOD) and enhancing its antioxidant capacity [32]. Glucomannan AABP-2B, isolated and purified from Anemarrhena asphodeloides, demonstrates its hypoglycemic effect by inhibiting α-glucosidase activity and activating irS-1/PI3K/Akt signaling pathway in insulin-resistant cells [52]. Effects of glucomannan on insulin sensitivity contribute to weight loss, and taking as little as 4 g of glucomannan per day can promote weight loss [53].

2.2. Daily Application

2.2.1. Cosmetics

D. catenatum extracts are used as cosmetic raw materials to effectively solve the skin problems caused by yin deficiency and fire hyperactivity due to their rich polysaccharides, flavonoids, and other nutrients that are absorbed through the skin and have good moisturizing, anti-aging, and anti-wrinkle effects [54]. The aqueous extract of D. catenatum can resist drying damage to epidermal cells, increase cell vitality, and improve skin moisture content [55]. D. catenatum polysaccharide DSP has strong antioxidant activity, can scavenge DPPH free radicals, and has a better inhibitory effect on lipid peroxidation and oxidative damage of red blood cells [56][57]. Macromolecular polysaccharide as the main moisturizing component in D. catenatum is a kind of polyhydroxyl polymer, whose polar groups can form hydrogen bonds with water molecules to bind water. Meanwhile, polysaccharide can form a uniform film on the skin surface to prevent water loss [58]. Dendrobium huoshanense polysaccharide has certain hygroscopic and moisturizing properties with a higher moisture retention rate than glycerin, is non-irritating to skin, and serves as a natural moisturizing agent [59]. So far, many related skin care products are popular in the market, such as moistening and skin brightening masks with D. catenatum (SENYU, Jinhua, China), Dendrobium emulsion (MISS QUEEN, Ningbo, China), and D. catenatum skin corset firming lotion (BOTANIERA, Hangzhou, China).

2.2.2. Food and Functional Food

Glucomannan has wide application prospects in the food industry and can be used as a food additive, meal substitute food, and health care products, such as Tiepifengdou capsules, oral liquid, decoction pieces, yogurt [60], teabags [61][62], beverages, and noodles [63], and has been applied to a number of patents [64]. Due to its large molecular weight and strong water binding ability, glucomannan has excellent hydrophilicity, gelation, emulsification, film formation, thickening, and other unique functional properties [65]. With alkali treatment, the acetyl group in glucomannan is removed to promote the formation of intramolecular and intermolecular hydrogen bonds and get a gel with excellent stability [66]. Glucomannan is a licensed food additive, which is used as a stabilizing, thickening, and gellating agent [67]. For example, in yogurt and other drinks, glucomannan can be used as a thickening agent to increase flavor and nutrition [67]. In sausages, hams, and other meat products, glucomannan can replace fat, reduce fat content, increase viscosity, and water retention, to improve the texture and flavor of meat [68]. In starch products, the addition of glucomannan affects the paste characteristics, rheological properties, and texture of the starch system [69]. In addition, glucomannan can be used for food preservation, such as glucomannan film, which has good stability and food applicability and can be used for fruit and vegetable coating preservation and flavor microcapsule production [70].

3. Glucomannan Biosynthesis Pathway in Plant

In the biosynthesis pathway of glucomannan, the photosynthates of leaves are transported to the D. catenatum stem in the form of sucrose, which is then decomposed into glucose (Glc), UDP glucose (UDP-Glc), and fructose (Fru) under the action of sucrose synthase (SUS) and invertase (INV), and then, under the action of hexokinase (HXK) and fructokinase (FRK), Glc-6-P is further catalyzed by phosphoglucomutase (PGM) to produce glucose-1-phosphate (Glc-1-P). At the same time, Fru-6-P is catalyzed by phosphate mannose isomerase (PMI) to produce mannose-6-phosphate (Man-6-P), which is converted to mannose-1-phosphate (Man-1-P) by phosphomannomutase (PMM). GDP mannose pyrophosphorylase (GMP) catalyzes the production of GDP mannose (GDP-Man). Glc-1-P is converted to GDP-glucose (GDP-Glc) by GDP-Glc pyrophosphorylase (GGP) and Glc-1-P is also converted to ADP-glucose (ADP-Glc) by ADP-Glc pyrophosphorylase (AGP). Subsequently, GDP-Man, GDP-Glu, or ADP-Glu are each transported into the Golgi apparatus by specific transporters, and they are used as substrates of cellulose-like synthases A/D (CSLA/D) to synthesize glucomannan. Additionally, GDP-Man is also used for the synthesis of vitamin C/ascorbic acid (AsA) [71]. Glucomannan synthesized in the Golgi matrix might have two roles. On the one hand, it is localized in the cell wall through vesicle transport and functions as a structural polysaccharide [72]. On the other hand, glucomannan also acts as a storage polysaccharide in some plants, such as D. catenatum, Konjac, and A. vera. In Konjac, glucomannan was discovered to accumulate in the egg-shaped idioblast within the parenchyma [2].

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