Medicinal Plant Research 2025, Vol.15, No.1 http://hortherbpublisher.com/index.php/mpr © 2025 HortHerb Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved.
Medicinal Plant Research 2025, Vol.15, No.1 http://hortherbpublisher.com/index.php/mpr © 2025 HortHerb Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. Publisher HortHerb Publisher Editedby Editorial Team of Medicinal Plant Research Email: edit@mpr.hortherbpublisher.com Website: http://hortherbpublisher.com/index.php/mpr Address: 11388 Stevenston Hwy, PO Box 96016, Richmond, V7A 5J5, British Columbia Canada Medicinal Plant Research (ISSN 1927-6508) is an open access, peer reviewed journal published online by HortHerb Publisher. The journal publishes all the latest and outstanding research articles, letters and reviews in all aspects of medicinal plant research, including plant growth and development, plant biology, plant nutrition, medicinal properties, phytochemical constituents, fitoterapia, pharmacognosy, essential oils, ethno- pharmacology agronomic management, and phytomedicine, as well as chemistry, pharmacology and use of medicinal plants and their derivatives. HortHerb Publisher is an international Open Access publisher specializing in horticulture, herbal sciences, and tea-related research registered at the publishing platform that is operated by Sophia Publishing Group (SPG), founded in British Columbia of Canada. All the articles published in Medicinal Plant Research are Open Access, and are distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. HortHerb Publisher uses CrossCheck service to identify academic plagiarism through the world’s leading plagiarism prevention tool, iParadigms, and to protect the original authors’ copyrights.
Medicinal Plant Research (online), 2025, Vol. 15, No.1 ISSN 1927-6508 http://hortherbpublisher.com/index.php/mpr © 2025 HortHerb Publisher, registered at the publishing platform that is operated by Sophia Publishing Group, founded in British Columbia of Canada. All Rights Reserved. Latest Content The Interaction Between Ganoderma lucidumPolysaccharides and Gut Microbiota: Implications for Immune Health Zhichao Chen, Haijuan Zhang Medicinal Plant Research, 2025, Vol. 15, No. 1, 1-11 The Influence of Fertilization Strategy on the Active Ingredient Content and Yield of Female Motherwort Minghui Zhao, Xiazhen Huang Medicinal Plant Research, 2025, Vol. 15, No. 1, 12-19 The Role of Medicinal Food Substances in Chronic Disease Prevention and Health Promotion Huixian Li, Chuchu Liu Medicinal Plant Research, 2025, Vol. 15, No. 1, 20-31 Study on the Extraction of Active Components from Sapindus Fruits and Their Application in Biopesticides Jie Huang, Haomin Chen Medicinal Plant Research, 2025, Vol. 15, No. 1, 32-39 The Study of the Synergistic Effects of Purple Mussels and Other Ingredients in Lipid-Lowering Function Linhua Zhang, Jianhui Li Medicinal Plant Research, 2025, Vol. 15, No. 1, 40-50
Medicinal Plant Research 2025, Vol.15, No.1, 1-11 http://hortherbpublisher.com/index.php/mpr 1 Research Insight Open Access The Interaction Between Ganoderma lucidum Polysaccharides and Gut Microbiota: Implications for Immune Health Zhichao Chen1, Haijuan Zhang2 1 Department of Traditional Chinese Medicine, Longquan People’s Hospital, Longquan, Zhejiang, 323000, China 2 Longquan Agricultural and Rural Bureau, Longquan, Zhejiang, 323700, China Corresponding author: 305755091@qq.com Medicinal Plant Research, 2025, Vol.15, No.1 doi: 10.5376/mpr.2025.15.0001 Received: 08 Dec., 2024 Accepted: 10 Jan., 2025 Published: 21 Jan., 2025 Copyright © 2025 Chen and Zhang, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Chen Z.C., and Zhang H.J., 2025, The interaction between Ganoderma lucidum polysaccharides and gut microbiota: implications for immune health, Medicinal Plant Research, 15(1): 1-11 (doi: 10.5376/mpr.2025.15.0001) Abstract Ganoderma lucidumpolysaccharides (GLPs) are natural polysaccharide compounds extracted fromGanoderma lucidum, known for their diverse biological activities. This study explores the interaction between GLPs and gut microbiota and its effects on immune health, revealing how GLPs regulate immune responses through gut microbiota and investigating their potential applications in preventing and treating immune-related diseases. The study shows that GLPs can increase the production of short-chain fatty acids, regulate the proportion of beneficial gut bacteria, and alleviate inflammatory responses by modulating the TLR4/MyD88/NF-κB signaling pathway. The results indicate that GLPs significantly improve gut microbiota imbalance, enhance macrophage phagocytosis, and increase the cytotoxicity of natural killer cells, demonstrating their potential in immune regulation and disease prevention. Future research will focus on further uncovering the molecular mechanisms of GLPs and their long-term application potential in human health. Keywords Ganoderma lucidumpolysaccharides; Gut microbiota; Immune health; Interaction; Disease prevention 1 Introduction Ganoderma lucidum is a medicinal mushroom with a long history of use in traditional Chinese medicine. The polysaccharides derived from G. lucidum (GLPs) are notable for their diverse biological activities, including antioxidant, antitumor, anti-inflammatory, antiviral, anti-diabetes, and immunomodulatory effects (Wachtel-Galor et al., 2011; Lu et al., 2020). These polysaccharides are characterized by their complex molecular structures, which include variations in molecular weight, branching, and monosaccharide composition (Lu et al., 2020). The gut microbiota, a complex community of microorganisms residing in the gastrointestinal tract, plays a crucial role in maintaining host health. It is involved in various physiological processes, including digestion, metabolism, and the modulation of the immune system. The composition and function of the gut microbiota can be influenced by diet, lifestyle, and the intake of bioactive compounds such as polysaccharides (Kubota et al., 2018; Li et al., 2020). The gut microbiota is integral to the development and function of the host's immune system. It contributes to the maturation of immune cells, the production of antimicrobial peptides, and the regulation of inflammatory responses (Kubota et al., 2018). The interaction between the gut microbiota and the immune system is bidirectional; while the microbiota influences immune function, the immune system also shapes the composition of the gut microbiota. Disruptions in this delicate balance can lead to immune-related disorders, including allergies, autoimmune diseases, and infections (Kubota et al., 2018; Li et al., 2020). Understanding the interaction between GLPs and gut microbiota is of great significance. Research has shown that GLPs can regulate immune responses, potentially mediated through their effects on the gut microbiota (Chen et al., 2019). This regulatory effect can improve gut barrier function, reduce inflammatory responses, and enhance immune function (Jin et al., 2017; Guo et al., 2021). For example, GLPs can increase the production of immunoglobulin A (IgA) and antimicrobial peptides in the gut, strengthening the gut barrier and reducing the risk of infection (Kubota et al., 2018). Additionally, the effects of GLPs on the gut microbiota can have systemic
Medicinal Plant Research 2025, Vol.15, No.1, 1-11 http://hortherbpublisher.com/index.php/mpr 2 impacts, potentially offering therapeutic benefits for diseases such as obesity, diabetes, and cancer (Chang et al., 2015; Sang et al., 2021). These interactions may have profound implications for developing novel therapeutic strategies aimed at enhancing immune health through dietary interventions. This study explores the interaction between Ganoderma lucidumpolysaccharides (GLPs) and gut microbiota, and their effects on immune health, particularly focusing on how GLPs regulate the composition and function of gut microbiota, identifying microbial metabolites involved in immune modulation, and assessing their overall impact on immune function. The study anticipates that GLPs will promote the growth of beneficial gut bacteria, improve gut barrier integrity, and modulate immune responses, thereby offering potential therapeutic strategies for immune-related diseases. This study attempts to provide new insights into the role of dietary polysaccharides in regulating the gut microbiota and supporting immune health, while also offering theoretical foundations and references for the development of disease interventions based on GLPs. 2 Chemical Composition and Biological Activities of Ganoderma lucidumPolysaccharides 2.1 Structural characteristics Ganoderma lucidum polysaccharides (GLPs) are composed of various monosaccharides, including glucose, galactose, and mannose. Their specific composition varies depending on the extraction method and the part of the G. lucidumused. For instance, GLP-1 and GLP-2 are purified fromG. lucidumvia gradient ethanol precipitation and anion-exchange chromatography, respectively (Li et al., 2019). Structural characterization has shown that GLP-1 is a D-galactoglucan containing →6)-β-D-glucose (Glcp)- and →6)-α-D-galactose (Galp)- residues, with a random linear conformation. In contrast, GLP-2 is a spherical β-D-glucan composed of →6)-β-D-Glcp and →3)-β-D-Glcp residues. The molecular weight of Ganoderma lucidumpolysaccharides (GLPs) ranges from several thousand to millions, which significantly affects their biological functions. GLPs exhibit various structural features, including both linear and branched conformations. For example, GLP-1, with a flexible random linear conformation, demonstrates superior immunomodulatory activity, effectively protecting the spleen and thymus, promoting hematopoiesis, and increasing serum IgA levels (Li et al., 2019). On the other hand, GLP-3, extracted from Ganoderma lucidum, is a spherical polysaccharide with immunomodulatory properties. Its main chain is composed of α-D-glucose, and research has shown that GLP-3 enhances immune regulation by activating specific signaling pathways, which is related to its tertiary helical structure (Gao et al., 2020). 2.2 Immunomodulatory effects Studies have found that Ganoderma lucidum polysaccharides (GLPs) can activate innate immune cells. For example, GLPs can regulate macrophage polarization through the MAPK/NF-κB signaling pathway, enhancing the expression of the M1 phenotype (pro-inflammatory) and inhibiting the M2 phenotype (anti-inflammatory), thereby suppressing tumor cell growth (Li et al., 2018; 2023). Additionally, GLPs can modulate the gut microbiota by inhibiting the TLR4/MyD88/NF-κB signaling pathway, improving intestinal barrier function, reducing the expression of inflammatory markers, and thus alleviating colonic inflammation and tumorigenesis (Guo et al., 2021). GLPs can modulate the production of various cytokines, which are signaling molecules that mediate and regulate immunity, inflammation, and hematopoiesis. For example, GLP treatment has been shown to downregulate pro-inflammatory cytokines such as IL-1β, iNOS, and COX-2, thereby reducing inflammation (Guo et al., 2021). And GLPs can enhance the production of anti-inflammatory cytokines, contributing to their overall immunomodulatory effects (Li et al., 2019). 2.3 Extraction and purification techniques Hot water extraction (HWE) is one of the most commonly used methods for extracting Ganoderma lucidum polysaccharides. This method involves boiling G. lucidummaterials in water to dissolve the polysaccharides. The extract is then concentrated and purified using techniques such as ethanol precipitation and ion-exchange chromatography (Zheng et al., 2022). This method is highly effective in yielding polysaccharides with significant
Medicinal Plant Research 2025, Vol.15, No.1, 1-11 http://hortherbpublisher.com/index.php/mpr 3 biological activity. One study found that polysaccharides extracted using HWE had a relatively large molecular weight, reaching 703.45 kDa (Kang et al., 2019). Enzymatic extraction, on the other hand, utilizes specific enzymes to break down the cell walls of G. lucidum, releasing the polysaccharides. Compared to hot water extraction, this method may be more efficient and selective. A study comparing different extraction methods-including hot water extraction, ultrasound-assisted extraction, and enzyme-assisted extraction-showed that enzyme-assisted extraction produced polysaccharides with higher content and antioxidant activity, outperforming traditional hot water extraction, particularly in terms of immunomodulatory effects (Liu et al., 2021). For example, polysaccharides extracted through enzyme-assisted methods significantly enhanced macrophage proliferation and cytokine secretion, especially promoting the production of NO, TNF-α, and IL-6. 3 Gut Microbiota and Its Role in Human Health 3.1 Composition and diversity of gut microbiota The human gut microbiota is a complex ecosystem primarily composed of bacteria, with the major phyla being Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. Specific species within these phyla play crucial roles in maintaining gut health. For instance, beneficial bacteria such as Bacteroides and Blautia are known to support metabolic functions and immune health, while harmful bacteria like Aerococcus and Proteus can contribute to disease states (Chen et al., 2019; Lv et al., 2019). Gut microbiota perform essential functions, including the fermentation of indigestible carbohydrates to produce short-chain fatty acids (SCFAs), which are vital for colon health and energy metabolism. They also play a role in synthesizing vitamins, metabolizing bile acids, and modulating the immune system. The metabolic activities of gut microbiota are influenced by their composition, which can be altered by dietary components such as polysaccharides fromGanoderma lucidum(Chen et al., 2019; Guo et al., 2020; Guo et al., 2021). 3.2 Factors influencing gut microbiota balance Diet is a primary factor influencing the composition and function of gut microbiota. High-fat diets can lead to dysbiosis, characterized by a decrease in beneficial bacteria and an increase in harmful species. Conversely, dietary polysaccharides from Ganoderma lucidum have been shown to modulate gut microbiota positively, increasing the abundance of beneficial bacteria like Bacteroides and reducing harmful bacteria such as Ruminococcus (Lv et al., 2019; Sang et al., 2021; Zheng et al., 2022). Antibiotics can severely disrupt the gut microbiota, leading to decreased microbial diversity, dysbiosis, and potentially impairing gut barrier function and immune responses. However, combining antibiotics with prebiotics such as Ganoderma lucidum polysaccharides can mitigate these adverse effects by promoting the growth of beneficial bacteria and enhancing the integrity of the gut barrier (Li et al., 2023). For example, studies have found that the use of ciprofloxacin (an antibiotic) alone damages the gut barrier, while GLPs alleviate the negative effects of antibiotics on the gut by increasing the concentration of tight junction proteins such as ZO-1 and Occludin. 3.3 Interaction between gut microbiota and immune system The gut microbiota plays a crucial role in the development and function of the immune system, promoting the maturation of immune cells and contributing to the production of immunoregulatory compounds. Gut microbiota dysbiosis is linked to various immune disorders, including inflammatory bowel disease (IBD) and metabolic syndrome (Tong et al., 2019). Studies have shown that GLPs can enhance immune function by modulating the gut microbiota, thereby increasing the activity of macrophages and the cytotoxicity of natural killer (NK) cells (Wu et al., 2020; Su et al., 2021). Further research by Guo et al. (2021) demonstrated that GLPs can improve gut microbiota imbalance, increase the production of short-chain fatty acids, and alleviate endotoxemia. And GLPs reduce the risk of immune-related diseases by inhibiting inflammation-related signaling pathways, such as the TLR4/MyD88/NF-κB pathways
Medicinal Plant Research 2025, Vol.15, No.1, 1-11 http://hortherbpublisher.com/index.php/mpr 4 (Tong et al., 2019; Guo et al., 2021). Moreover, broken-spore polysaccharides fromGanoderma lucidum have been shown to effectively inhibit obesity, inflammation, and fat accumulation induced by a high-fat diet by modulating the gut microbiota and improving gut barrier function (Sang et al., 2021). 4 Interaction BetweenG. lucidumPolysaccharides and Gut Microbiota 4.1 Modulation of gut microbiota by G. lucidumpolysaccharides Ganoderma lucidumpolysaccharides (GLPs) have been shown to significantly modulate the composition of gut microbiota. Studies have demonstrated that GLPs can restore the balance of gut microbiota in various disease models. For instance, GLPs were found to reduce the abundance of harmful bacteria such as Aerococcus, Ruminococcus, Corynebacterium, and Proteus, while increasing beneficial bacteria like Blautia, Dehalobacterium, Parabacteroides, and Bacteroides in type 2 diabetic rats (Chen et al., 2019). A study on rats fed a high-fat diet revealed that GLPs can alleviate lipid metabolism disorders and impaired gut barrier function caused by the high-fat diet by modulating the gut microbiota, such as increasing the abundance of beneficial bacteria like Prevotella (Tong et al., 2019). In a colon cancer model, GLPs significantly improved symptoms of colitis and colon cancer by reducing the expression of inflammatory factors and modulating the gut microbiota, such as decreasing cancer-associated bacteria like Oscillospira. These findings highlight the potential of GLPs in cancer prevention and treatment (Luo et al., 2018). The results suggest that GLPs may serve as potential prebiotics, promoting the growth of beneficial gut microbes while inhibiting harmful bacteria. 4.2 Mechanisms of interaction at molecular level The interaction between GLPs and gut microbiota involves several molecular mechanisms. GLPs have been shown to influence the gut microbiota through their structural characteristics, such as molecular weight, monosaccharide composition, and glycosidic bonds (Li et al., 2019; Lu et al., 2020). These structural features determine the physicochemical properties and biological activities of GLPs, which in turn affect their interaction with gut microbiota. For example, GLPs can bind to receptors on immune cells, such as dectin-1 on macrophages, monocytes, dendritic cells, and neutrophils, leading to the activation of signaling pathways like MAPKs and NF-κB, which are involved in cytokine production and immune response (Ahmad et al., 2021). The results indicate that GLPs can enhance the activity of T cells and macrophages, increasing the production of important cytokines such as IL-2 and TNF-α, thereby boosting the overall immune response (Figure 1). Furthermore, GLPs have been shown to modulate the gut microbiota by enhancing gut barrier function, increasing the number of goblet cells, and promoting the secretion of mucins and tight junction proteins (Guo et al., 2021). 4.3 Influence on microbial metabolites GLPs not only modulate the composition of gut microbiota but also influence the production of microbial metabolites. For instance, GLPs have been reported to increase the production of short-chain fatty acids (SCFAs), which are beneficial metabolites produced by gut bacteria through the fermentation of dietary fibers (Guo et al., 2021). SCFAs play a crucial role in maintaining gut health by providing energy to colonocytes, regulating immune responses, and protecting against inflammation and tumorigenesis. GLPs have been shown to restore disturbed amino acid, carbohydrate, and nucleic acid metabolism in the gut microbiota of type 2 diabetic rats, indicating their potential to normalize metabolic functions (Chen et al., 2019). Moreover, GLPs have been found to regulate the levels of key metabolites such as dopamine, prolyl-glutamine, and L-threonine, which are associated with immune enhancement and overall health (Wu et al., 2020). These findings highlight the significant impact of GLPs on microbial metabolites and their potential therapeutic benefits.
Medicinal Plant Research 2025, Vol.15, No.1, 1-11 http://hortherbpublisher.com/index.php/mpr 5 Figure 1 G. lucidumpolysaccharides produce immunomodulatory action through promoting antigen-presenting cells, mononuclear phagocyte system, humoral and cellular immunity (Adopted from Ahmad et al., 2021) Image Caption: The figure illustrates how Ganoderma lucidum polysaccharides (GLPs) produce immunomodulatory effects by promoting antigen-presenting cells, the mononuclear phagocyte system, humoral, and cellular immunity. The figure details the mechanism of GLPs in activating T cells and increasing cytokine production, such as IL-2 and TNF-α. The results indicate that GLPs can enhance the body's immune response through multiple immune pathways, showing significant potential, particularly in antiviral and anti-infection applications (Adapted from Ahmad et al., 2021) 5 Case Studies 5.1 Study on the inhibitory effects of G. lucidumpolysaccharides on colitis-associated cancer Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. Its occurrence is associated with multiple factors, such as environmental, dietary, genetic, and epigenetic influences (Kendong et al., 2021). Gut microbiota dysbiosis is considered a key factor in inducing chronic inflammation and promoting CRC development. In recent years, research on the prevention of CRC through prebiotics and dietary fibers, which modulate gut microbiota, has been increasing. G. lucidum polysaccharides (GLPs), as a significant bioactive substance, have garnered attention for their immunoregulatory and anticancer properties (Chattopadhyay et al., 2021; Guo et al., 2021). Guo et al. (2021) explored the effects of GLPs on an AOM/DSS-induced mouse model of colitis and tumorigenesis. The study found that GLP increased the production of short-chain fatty acids (SCFAs), inhibited the TLR4/MyD88/NF-κB signaling pathway, and reduced macrophage infiltration and the expression of inflammatory markers (Figure 2). Additionally, GLP showed the ability to suppress LPS-induced inflammatory markers in in vitro experiments. The results suggest that GLP can significantly reduce tumor size and number, improve inflammatory responses, and enhance intestinal barrier function by modulating gut microbiota, providing a new research direction for CRC prevention and treatment.
Medicinal Plant Research 2025, Vol.15, No.1, 1-11 http://hortherbpublisher.com/index.php/mpr 6 Figure 2 Schematic showing the role of GLP in modulating the intestinal microbiota and its relationship with inflammation and tumorigenesis in AOM/DSS mice (Adopted from Guo et al., 2021) Image caption: The figure reveals the mechanism by which GLP modulates the structure of the gut microbiota, increases the production of short-chain fatty acids (SCFAs), and improves intestinal barrier function, thereby inhibiting inflammation and tumorigenesis. GLP suppresses the TLR4/MyD88/NF-κB and MAPK (ERK and JNK) signaling pathways, reducing macrophage infiltration and pro-inflammatory cytokine expression, ultimately lowering the risk of colitis and tumor formation (Adapted from Guo et al., 2021) 5.2 Study on the immunomodulatory effects of sporoderm-brokenG. lucidumspore polysaccharides G. lucidum spores are the reproductive cells of the fungus, and their outer walls are relatively hard, usually requiring sporoderm-breaking treatment to extract the active components. Both G. lucidumpolysaccharides and G. lucidumspore polysaccharides are polysaccharides in chemical structure, but due to differences in their extraction sources, their molecular weight, glycan chain structure, and accompanying bioactive compounds may differ, leading to variations in their biological activities (Wu et al., 2020). Crude polysaccharides and refined polysaccharides from G. lucidum spores (CPGS and RPGS) are specific types of G. lucidum spore polysaccharides, belonging to the G. lucidum(GLPs) family. They differ from traditional GLPs in terms of source, composition, and bioactivity. After sporoderm-breaking, the polysaccharide components of G. lucidum spores exhibit higher bioavailability (Sang et al., 2021; Su et al., 2021). Compared to GLPs, CPGS and RPGS have distinct advantages in immune regulation and gut microbiota modulation, especially RPGS, which, due to its higher purity, demonstrates stronger immunostimulatory effects (Su et al., 2021). The study by Su et al. (2021) evaluated the immunomodulatory effects of CPGS and RPGS on the immune system in mice. The results showed that CPGS significantly enhanced the tumor-killing ability of natural killer cells, while RPGS notably increased the proportion of T cells and their subsets in peripheral blood and promoted T cell activation. Additionally, 16S rRNA sequencing analysis of the gut microbiota revealed that CPGS and RPGS reshaped the gut microbiome, enriching polysaccharide-metabolizing bacteria such as Adlercreutzia and Prevotella, which were closely related to T cell activity. The findings indicate that G. lucidum spore polysaccharides can significantly enhance the function of the adaptive immune system by regulating the gut microbiota and immune cell activity, further supporting their potential application in promoting health.
Medicinal Plant Research 2025, Vol.15, No.1, 1-11 http://hortherbpublisher.com/index.php/mpr 7 5.3 Prebiotic effects of G. lucidumpolysaccharides (GLPs) in a human intestinal microbial ecosystem In recent years, the prebiotic potential of G. lucidumpolysaccharides (GLPs) has garnered increasing attention. Prebiotics can promote the growth of beneficial gut microbes, regulate the host's intestinal environment, and provide health benefits (Guo et al., 2021; Sang et al., 2021). To better understand the metabolic and microbial regulatory effects of GLPs in the gut, a study employed the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) to evaluate the impact of GLPs on human fecal microbiota. The results showed that GLPs served as a carbon source for gut microbiota, significantly increasing the production of short-chain fatty acids (such as acetic, propionic, and butyric acids) and lowering intestinal pH, thus inhibiting the growth of potential pathogens (Yang et al., 2022). GLPs also modulated the gut microbiota, notably enhancing the abundance of Bacteroidetes, particularly enriching Bacteroides ovatus and B. uniformis, which are closely associated with improved metabolic function and enhanced immune regulation (Figure 3). Figure 3 LEfSe analysis and PICRUSt2 analysis of microbiota between the GLP group and the BLK group at ASV level. (A) LDA scores with corresponding phylum, genus and species (LDA score>4.0 was shown) and (B) Cladogram of the bacteria taxa. (C) LDA scores of differential metabolic pathways. BLK, blank group; GLP, polysaccharides from fruiting bodies of Ganoderma lucidum (Adopted from Yang et al., 2022) Image caption: The figure shows the impact of G. lucidum polysaccharides (GLPs) on gut microbial metabolic functions and the abundance of specific bacterial taxa. Figures A and B, analyzed by LEfSe, demonstrate that the GLP group significantly enriched Bacteroidetes and Proteobacteria, while the control group showed enrichment of Firmicutes and Fusobacteria. Figure C presents the PICRUSt2 functional analysis, indicating significant differences in metabolic pathways, such as glycogen degradation and secondary metabolite synthesis, between the GLP group and the control group. These results reveal that GLPs not only alter microbial composition but also significantly affect their metabolic functions, confirming their potential in regulating gut metabolic health (Adapted from Yang et al., 2022)
Medicinal Plant Research 2025, Vol.15, No.1, 1-11 http://hortherbpublisher.com/index.php/mpr 8 The study suggests that GLPs, as a prebiotic, has potential anti-inflammatory and metabolic health benefits by regulating gut microbiota and their metabolites, providing scientific support for its further application in gut health. 6 Potential Applications in Functional Foods and Medicine 6.1 Use in functional foods for gut health improvement Ganoderma lucidum polysaccharides (GLPs) have shown significant potential as functional food ingredients aimed at improving gut health. Studies have demonstrated that GLPs can modulate gut microbiota composition, enhancing the abundance of beneficial bacteria such as Bacteroides, Parabacteroides, and Lactobacillus, while reducing harmful bacteria like Aerococcus and Ruminococcus (Chang et al., 2015; Chen et al., 2019; Zheng et al., 2022). This modulation leads to improved gut barrier function, increased production of short-chain fatty acids (SCFAs), and reduced endotoxemia, which collectively contribute to better gut health (Guo et al., 2021; Sang et al., 2021; Li et al., 2023). Additionally, GLPs has been found to alleviate gut microbiota dysbiosis induced by high-fat diets and antibiotics, further supporting its role as a prebiotic agent in functional foods (Sang et al., 2021; Li et al., 2023). 6.2 Pharmaceutical applications for immune health The immunomodulatory properties of GLP make it a promising candidate for pharmaceutical applications aimed at enhancing immune health. Research has shown that GLP can enhance macrophage phagocytosis, natural killer (NK) cell cytotoxicity, and overall immune cell function (Wu et al., 2020; Guo et al., 2021). These effects are mediated through the modulation of gut microbiota, which in turn influences the production of key metabolites involved in immune responses (Jin et al., 2019; Wu et al., 2020). Furthermore, GLP has demonstrated anti-inflammatory and anticancer properties by inhibiting pro-inflammatory cytokines and oncogenic signaling pathways, making it a potential therapeutic agent for conditions like colorectal cancer and chronic inflammation (Khan et al., 2019; Guo et al., 2021). The ability of GLP to restore gut microbiota balance and improve metabolic profiles in diabetic models also highlights its potential in managing metabolic disorders (Chen et al., 2019). 6.3 Challenges in commercialization Despite the promising applications of GLPs in functional foods and pharmaceuticals, several challenges need to be addressed for successful commercialization. One major challenge is the standardization of GLPs extraction and purification processes to ensure consistent quality and bioactivity (Zheng et al., 2022; Swallah et al., 2023). Variability in the structural characteristics of GLPs, such as molecular weight and monosaccharide composition, can affect its efficacy and safety, necessitating rigorous quality control measures (Zheng et al., 2022). Additionally, the scalability of GLPs production and the cost-effectiveness of manufacturing processes are critical factors that need optimization. Regulatory hurdles related to the approval of GLPs as a functional food ingredient or pharmaceutical agent also pose significant challenges. Comprehensive toxicological studies and clinical trials are required to establish the safety and efficacy of GLPs, which can be time-consuming and costly (Swallah et al., 2023). Addressing these challenges through collaborative research and development efforts will be essential for the successful commercialization of GLPs-based products. 7 Future Research Directions 7.1 Understanding specific gut microbial strains involved Future research should focus on identifying specific gut microbial strains that are positively influenced by Ganoderma lucidum polysaccharides (GLPs). Studies have shown that GLPs can increase the abundance of beneficial bacteria such as Lactobacillus, Turicibacter, and Romboutsia, while reducing harmful bacteria like Staphylococcus and Helicobacter (Wu et al., 2020). Additionally, GLPs has been found to enrich bacteria such as Adlercreutzia, Parabacteroides, and Prevotella, which are associated with immune regulation (Su et al., 2021). Identifying these key strains can help in understanding the precise mechanisms through which GLP exerts its beneficial effects. The role of microbial metabolites in mediating the immune response is another critical area for future research. GLP has been shown to modulate a range of metabolites, including short-chain fatty acids (SCFAs) and other bioactive compounds like dopamine and prolyl-glutamine, which are linked to immune
Medicinal Plant Research 2025, Vol.15, No.1, 1-11 http://hortherbpublisher.com/index.php/mpr 9 enhancement (Wu et al., 2020; Guo et al., 2021). Understanding how these metabolites interact with the host immune system can provide deeper insights into the immunomodulatory effects of GLPs. 7.2 Long-term effects of Ganoderma lucidumpolysaccharides consumption Long-term studies are needed to evaluate the sustained immunomodulatory benefits of GLPs. While short-term studies have demonstrated enhanced macrophage phagocytosis and NK cell cytotoxicity (Wu et al., 2020), it is essential to investigate whether these benefits persist over extended periods. This will help in determining the long-term efficacy of GLPs as an immune-boosting supplement. The safety and tolerability of long-term GLPs consumption should also be a focus of future research. Although current studies have not reported significant adverse effects, comprehensive long-term studies are necessary to ensure that GLPs is safe for prolonged use (Jin et al., 2019). This will involve monitoring for any potential side effects and assessing the overall health impact of extended GLP consumption. 7.3 Integration with other prebiotics and probiotics Investigating the synergistic effects of GLPs when combined with other prebiotics is another promising research direction. GLPs has shown potential as a prebiotic by modulating gut microbiota and improving gut barrier function (Krumbeck et al., 2018; Chen et al., 2019). Combining GLPs with other prebiotics could enhance these effects, leading to improved gut health and immune function. The development of combined probiotic supplements that include GLPs is another area worth exploring. Studies have shown that GLP can increase the abundance of probiotic bacteria such as Lactobacillus and Bifidobacterium (Lv et al., 2019; Li et al., 2023). Formulating supplements that combine GLP with these probiotics could offer a more comprehensive approach to gut health and immune support. 8 Conclusion The interaction between G. lucidum polysaccharides (GLPs) and gut microbiota has shown significant implications for immune health. Studies have demonstrated that GLPs can modulate gut microbiota composition, enhance immune cell function, and improve gut barrier integrity. For instance, GLPs has been found to decrease inflammation and tumorigenesis in colitis models by modulating gut microbiota and increasing short-chain fatty acid production. And GLPs has been shown to enhance macrophage phagocytosis and NK cell cytotoxicity, correlating with changes in gut microbiota and metabolite profiles. Furthermore, GLPs administration has been linked to improved adaptive immune function and increased proportions of beneficial gut bacteria. These findings collectively suggest that GLPs act as a promising prebiotic with potential therapeutic benefits for immune health. Despite the promising results, several limitations exist in the current body of research. Most studies have been conducted in animal models, which may not fully replicate human physiological responses. The specific mechanisms by which GLP modulates gut microbiota and immune responses are not yet fully understood, necessitating further molecular and mechanistic studies. Additionally, variations in the extraction methods and dosages of GLP used across different studies may lead to inconsistent results, highlighting the need for standardized protocols. Long-term safety and efficacy studies in humans are required to validate the therapeutic potential of GLP for immune health. The findings from these studies suggest several potential implications for future health interventions. GLP could be developed as a dietary supplement or functional food ingredient aimed at enhancing immune health and preventing inflammatory diseases. Synergistic effects of GLP with other treatments, such as antibiotics, could be explored to mitigate the adverse effects of conventional therapies and improve patient outcomes. Future research should focus on clinical trials to establish the efficacy and safety of GLP in humans, as well as on elucidating the precise molecular pathways involved in its immunomodulatory effects. At the same time, personalized nutrition plans can be developed based on individual gut microbiota profiles to maximize the health benefits of GLP. Acknowledgments We sincerely thank Mr. Wang from the Ganoderma Research Group for assisting in collecting relevant literature and participating in the review and revision of the manuscript. We would also like to express my heartfelt gratitude to the two anonymous peer reviewers for their comprehensive evaluation of the manuscript.
Medicinal Plant Research 2025, Vol.15, No.1, 1-11 http://hortherbpublisher.com/index.php/mpr 10 Conflict of Interest Disclosure The authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. 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Medicinal Plant Research 2025, Vol.15, No.1, 12-19 http://hortherbpublisher.com/index.php/mpr 12 Feature Review Open Access The Influence of Fertilization Strategy on the Active Ingredient Content and Yield of Female Motherwort Minghui Zhao, Xiazhen Huang Tropical Medicinal Plant Research Center, Hainan Institute of Tropical Agricultural Resources, Sanya, 572025, Hainan, China Corresponding author: xiazhen.huang@hitar.org Medicinal Plant Research, 2025, Vol.15, No.1 doi: 10.5376/mpr.2025.15.0002 Received: 20 Dec., 2024 Accepted: 25 Jan., 2025 Published: 05 Feb., 2025 Copyright © 2025 Zhao and Huang, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Zhao M.H., and Huang X.Z., 2025, The influence of fertilization strategy on the active ingredient content and yield of female motherwort, Medicinal Plant Research, 15(1): 12-19 (doi: 10.5376/mpr.2025.15.0002) Abstract Fertilization management is the most important approach to regulating the quality and yield of medicinal plants, particularly the cultivation management of Leonurus japonicus (young motherwort). In recent years, research on the active constituents and yield of Leonurus japonicus has developed extensively. As one of the most significant agricultural managements, fertilization has attracted extensive concern because of its influence on the secondary metabolite accumulation (e.g., alkaloids, flavonoids, polysaccharides) and plant growth. The paper briefly reviews the work of the research on the impact of fertilization measures on Leonurus japonicus' content of active ingredients and yield, particularly the regulation mechanism of different nutrients (nitrogen, phosphorus, potassium, etc.) for secondary metabolism and yield enhancement. In addition, the paper also makes a discussion about the impact of fertilization on soil microecology and its potential effect on the ecological environment. The findings indicate that different fertilization combinations have very disparate impacts on the active constituents and yield of Leonurus japonicus. With scientifically optimized fertilization strategies, harmonious balance between quality and yield can be achieved. More significantly, the impacts of fertilization on the microbial communities in soils create new concepts for the improvement of fertilizer application efficiency and the realization of sustainable production. This study provides a theoretical foundation for future scientific fertilization management of Leonurus japonicus cultivation and a valuable reference for high-quality development and ecologically rational production regulations in the drug plant sector. Keywords Leonurus japonicus; Fertilization strategy; Active ingredients; Yield; Soil microecology 1 Introduction Leonurus japonicus, or young motherwort, is a medicinal plant indigenous and distributed largely in East Asian countries, particularly China and Japan. As Lamiaceae, it has been known since a long time ago for its pharmacological activity and attributed features including anti-inflammatory, antioxidant, and cardioprotective activity (Cai et al., 2018). Alkaloids, flavonoids, and polysaccharides are among the active ingredients in Leonurus japonicus that have significant contributions to make in the drug uses. With the increased demand for high-quality medicinal plants, the focus on enhancing L. japonicus yield and quality through cultivation has increased. L. japonicus development needs to be properly managed to achieve its optimal growth and biosynthesis of its bioactive compounds. Fertilization, which is one of the most critical cultivation processes, has been identified as one of the most powerful factors influencing plant development, yield, and secondary metabolite biosynthesis (Wang et al., 2020). Recent studies have also elaborated on the soil nutrient-metabolic process interaction of active compounds to provide a foundation for precision cultivation practices. Fertilization exerts dual effects on the agriculture of medicinal plants via direct influence on biomass production and biosynthesis of active metabolites. The ratio of the major nutrients such as nitrogen (N), phosphorus (P), and potassium (K) is particularly significant for metabolic processes towards the production of secondary metabolites (Zhang et al., 2019). A policy of optimal fertilization not only promotes the vegetative growth of the plants but also enhances the quality and yield of pharmacologically active constituents.
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