Research progress of Gastrodia elata Blume polysaccharides: a review of chemical structures and biological activities

Gastrodia elata Blume (G. elata), listed as one of the 34 precious Chinese medicines, servers a dual purpose as both a medicinal herb and a food source. Polysaccharide is the main active ingredient in G. elata, which has pharmacological activities such as immune regulation, anti-oxidation, anti-cancer, anti-aging, neuroprotection and antibacterial activity and so on. The biological activities of G. elata polysaccharide (GPs) is closely related to its chemical structures. However, no a review has synthetically summarized the chemical structures and pharmacological activities of GPs. This study delves into the chemical structures, pharmacological action of GPs, offering insights for the future development an application of these compounds.

with a wide range of pharmacological effects, such as anti-oxidant, anti-cancer, anti-virus, anti-osteoporosis, immunomodulatory, and neuroprotective effects and so on (Qiu et al., 2007;Chen et al., 2015;Liu and Mori, 1992;Liu et al., 2015;Bao et al., 2017).Due to its great medical and health value, more and more researchers are paying attention to the pharmacological activities of GPs.Furthermore, many studies have attested that the biological activities of GPs are closely related to their chemical structures.However, no previous articles have synthetically summarized the chemical structures and pharmacological activities of GPs.In this article, we review the structural characteristics, biological activities and structure-activity relationships of GPs, to aid in providing a theoretical basis and data for the research, development and utilization of GPs.

The structural features of GPs
The structures of polysaccharides can be divided into primary structure and high-level structure.The primary structure includes molecular weight, monosaccharide composition, glycosidic bond configuration, repeating structural units and branching degree.The high-level structure (secondary, tertiary and quaternary structures) Notes:-Indicates that the item is not detected; Glc: glucose, Man: mannose, Rha: rhamnose, Gal: galactose, Xyl: xylose, Fru: fructose, GlcA: glucuronic acid, GlaA: galacturonic acid.

Biological activities
In recent years, research has focused on the pharmacodynamics of GPs.Many references point out that GPs showed that significant pharmacological activies, sush as anti-oxidation, anti-tumor, immune regulation, anti-aging, improve memory, improve cerebral ischemia, reduce blood pressure, anti-bacterial effect and reduce blood lipid (Figure 2) (Zhu et al., 2019;Wang et al., 2022).The biological activities of GPs are summarized in Table 2.

Anti-aging activities
Many studies have shown that GPs can improve the expression of peroxidase and slow down the aging of organs and tissue.Li N. et al. (2023) reported that GPs had anti-aging effects in D-galactoseinduced senescence mice.GPs significantly increased SOD and GSH-Px activity and decreased MDA and NO contents in aging mice, and showed a good dose-dependent relationship.Xie et al. (2010) found that GPs can improve the learning and memory ability of D-galactose-induced aging mice, its mechanism is mainly related to oxidative metabolism in the body.The finding of Kong et al. (2005) displayed that GPs significantly increased the activities of SOD and CAT in the serum, liver, brain and heart tissue of aging mice, significantly inhibited the formation of MDA in the serum, liver, brain and heart tissue of aging mice, and significantly increased The health functions of GPs.
Frontiers in Chemistry frontiersin.org04 Yang et al. 10.3389/fchem.2024.1395222 the activity of GSH-Px in the serum of aging mice.The results indicated that GPs had better scavenging free radicals, decreasing MDA content and delaying cell aging.Chen et al. (2018b) found that intragastric administration of GEP significantly decreased the MDA levels but significantly increased SOD and GSH-Px activities in the sera and brains of D-galactose-induced aging mice as compared with those of the model group, indicated that GEP can effectively suppress oxidation-induced damage to the sera and brain tissues of D-galactose-induced aging mice.Wang and Liu (2019) found that GPs could delay skeletal muscle aging in mice by reducing the mRNA expression and protein levels of caspase-3, MURF-1 and MAFbX in muscle tissue.However, the molecular mechanism of anti-aging is not been clarified.

Anti-tumor activities
Numerous cell and animal model studies have shown that GPs can significantly inhibit the development of various types of cancer, such as colon cancer, liver cancer, pancreatic cancer, etc. Wang et al. (2014) found that the tumor growth of GPs was significantly inhibited at 90 mg/kg, and the inhibition rate was 27.6%.Liu et al. (2015) reported that GPs have a significant anti-cancer effect on H22 tumor-bearing mice, the results showed that the GPs inhibition rate on H22 cells was 44.7%.The mechanism is mainly related to GPs could increase the cell percentage in the G0/G1 phase and decrease cell percentage in the G2/M phase.Qiu et al. (2010) reported that WSS25 could inhibit the growth of xenografted hepatocellular cancer cells in nude mice, its mechanism is related to the blocking of BMP/Smad signaling by WSS25, as shown in Figure 3. Dai et al. (2021) investigated the anti-tumor activities of G. elata polysaccharides (PGEs) against MCF-7 cells in vitro.The results showed that the PGEs could inhibit the growth of MCF-7 cells by promoting late apoptosis and arresting at G2/M phase.Chen et al. (2011) investigated the anti-pancreatic cancer activities of WTMA against PANC-1 cell lines and showed no effect on the growth of PANC-1 cells.

Immunological activities
Numerous in vitro and in vivo studies have demonstrated the immunological activities of GPs.Li et al. (2016) found that GPs can regulate the levels of immunoglobulin (IgA, IgG, IgM) and hemolysin in mice, and increase the index of thymus and spleen.Li et al. (2015) reported that GPs significantly reduced the activity of ALT, AST, NO and the content of TNF-α and IL-1 in the serum of mice, inhibited the level of MAD in the liver, increased the activity of SOD and the concentration could significantly increase the proliferation ability of T and B lymphocytes in the spleen.The results indicated that GPs had a good protective effect against immunological liver injury in mice.Li F. et al. (2013) found that GEPs can effectively alleviate immunosuppression, the potential mechanism was related to the modulation of gut microbiota composition by GEPs and the resulting increased content of SCFAs.Chen et al. (2016) found that the two polysaccharides (RGP-1a and RGP-1b) have a significant impact on NO production and phagocytic activity of RAW264.7 macrophages.Compared to RGP-1a, RGP-1b, which has a smaller molecular weight and a uniform monosaccharide composition, exhibits superior immunological activities in RAW264.7 macrophages.Molecular weight and homogeneous composition may be key factors affecting the immunological activity of GPs.Bao et al. (2017) found that GPs can increase serum IL-2, TNF-α, IFN-g, IgG, IgA and IgM levels, as well as spleen and thymus indices of Kunming mice, showing that GPs could improve the immune function of immunosuppression model mice.Guan et al. (2022) observed the effect of GEP-1 on immune function by increasing phagocytic activities and induced release of cytokines (TNF-α, IL1-β) and nitric oxide (NO) in macrophages.

Neuroprotective activities
The neuroprotective effect of GPs on rat pheochromocytoma nerve cells (PC12) has recently attracted great attention.Zhou et al. (2013) found that GPs significantly could improve corticosterone (CORT)induced injury and cell morphology of PC12 cells, reduce the expression of BCL-12 and BAX protein, and inhibit the expression of caspase-3 protein.Zhou et al. (2017) reported that GPs play a protective role in nerve cells by reducing the level of intracellular toxic reactive oxygen species, reducing the release of LDH, and inhibiting the expression of GRP 78, X-BP-1, GADD153, caspase-9 and caspase-12.Zhang et al. (2023) reported that neutral polysaccharide from G. elata (NPGE) had potential effects on the neuropathology of cerebral ischemiareperfusion injury (CIRI).Its mechanism is related to that NPGE alleviates CIRI by attenuating ferroptosis-mediated neuroinflammation via the NRF2/HO-1 signaling pathway, the relevant mechanism is shown in Figure 4.In addition, GPs could increase the expression of antiapoptotic gene Bcl-2 in brain tissue reduce expression of apoptosis gene Bax, alleviating cerebral palsy, apoptosis of brain tissue, exerting neuroprotective activity (Wang et al., 2019).

Hypotensive effects
Numerous studies have demonstrated the blood pressure lowering effect of GPs.Angiotensin-converting enzyme (ACE) plays a significant role in the development of hypertension in the body.The mechanism of WSS25 in hepatocellular cancer cell lines.Frontiers in Chemistry frontiersin.orgMiao and Shen (2006) observed the effect of GPs on angiotensin Ⅱ (Ang Ⅱ) level, the results showed that Ang II levels were decreased and the NO levels were increased.Zhu et al. (2018) found that PGE had ACE inhibitory activity, the inhibition rate of PGE on ACE was calculated to be 74.40% and the IC 50 value was 0.66 mg/mL.Lee et al. (2012) reported that the acidic polysaccharide fraction from Gastrodia rhizome significantly reduced blood pressure in SHR fed a high-fat diet.

Antihyperlipidemic effect
Ming et al. ( 2012) reported effects of PGEB-3-H on total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C).The results showed that PGEB-3-H could reduce the content of TC and TG and increase the level of HDL-C, but had no significant effect on the LDL-C content.It can be seen that PGEB-3-H has a potential effect on lowering blood lipids and is related to the regulation of cholesterol content.Lee et al. (2012) studies showed that the hypolipidemic indexes (total cholesterol, triglyceride and low-density lipoprotein cholesterol levels) of the acidic polysaccharide groups were lower than those in the control group.These results indicated that acidic polysaccharide improve serum lipid levels.

Other activities
GPs has various structures and diverse pharmacological effects.A large number of studies have shown that GPs play an effective role in anti-bacterial activity, osteoporosis prevention, liver protective effects, memory improvement and skin care effectiveness.Chen et al. (2018c) found that GPs had an inhibitory effect on G − , G + and fungi.Chen et al. (2015) investigated that a sulfated polysaccharide (WSS25) extracted from the rhizome of G. elata inhibited RANKLinduced osteoclast formation in RAW264.7 cells and BMMs by blocking the BMP-2/Smad/Id1 signaling pathway.Shi et al. (2017) reported that GPs could improve the memory of rats with cerebral palsy by regulating neurotransmitter in the brain.A number of studies have applied GPs to develop a skin care product (Wang et al., 2016;Du and Chen, 2018;Zheng et al., 2018).Qiu et al. (2007) reported that WGEW and AGEW showed strong anti-dengue virus bioactivity.Chen et al. (2024) found that four heteropolysaccharides had an inhibitory effect on the anti-hyperglycaemic activity of α-amylase and α-glucosidase.Xu et al. (2023) reported that GPs had modulation of gut microbiota and improvement in metabolic disorders.

Conclusion
In conclusion, as a traditional Chinese medicine, G. elata is widely used in medicine, food and health products.G. elata polysaccharides are one of the main components of G. elata.Due to its pharmacological effects such as anti-oxidation, anti-tumor, immune regulation and memory improvement, it has attracted great attention from scientists in medicine and healthcare fields.In this paper, structural analysis and pharmacological activities of related research, further study of G. elata polysaccharides and rational application for reference.

FIGURE 4
FIGURE 4Schematic illustration of NPGE in BC cells through of the NRF2/HO-1 pathway.

TABLE 1
The chemical structures of Gastrodia elata Blume polysaccharides.

TABLE 2
Biological activities of GPs isolated from the Gastrodia elata.

TABLE 2 (
Continued) Biological activities of GPs isolated from the Gastrodia elata.