ABSTRACT
The effect of ball milling on the physicochemical properties and gut microbiota regulation of Poria cocos pachyman (PAC) was investigated. Ball milling reduced the particle size of PAC from 102 µm to 25.19 µm after 12 h, resulting in increasing particle uniformity. Scanning electron microscopy (SEM) revealed surface roughening and fragmentation of PAC after ball milling. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) indicated reduced crystallinity and increased hydroxyl group exposure in ball-milled PAC (BMP). Thermogravimetric analysis (TGA) showed decreased thermal stability in BMP. The optimal ball milled time was 7 h. Moisture contents in PAC and BMP-7 h were 10.30 ± 0.47 % and 10.72 ± 0.12 %, and carbohydrate contents were 81.02 ± 2.27 % and 74.54 ± 1.46 %. In vivo studies on mice demonstrated that both PAC and BMP-7 h increased diversity and reshaped the composition of gut microbiota, with BMP-7 h showing a more pronounced effect. BMP-7 h reduced the Firmicutes/Bacteroidetes ratio, and raised the abundance of Bacteroides, suggesting enhanced prebiotic potential. These findings highlight the role of ball milling in improving the physicochemical properties and prebiotic potential of water-insoluble polysaccharides and provide a theoretical basis for its broader application in the food and biopharmaceutical industries.
Subject(s)
Gastrointestinal Microbiome , Gastrointestinal Microbiome/drug effects , Animals , Mice , Wolfiporia/chemistry , Chemical Phenomena , Prebiotics , Particle Size , Thermogravimetry , X-Ray Diffraction , Spectroscopy, Fourier Transform Infrared , Bone Morphogenetic Protein 7/chemistryABSTRACT
The aim of this study was to investigate the key targets and molecular mechanisms of the drug pair Astragalus membranaceus and Poria cocos (HFDP) in the treatment of immunity. We utilized network pharmacology, molecular docking, and immune infiltration techniques in conjunction with data from the GEO database. Previous clinical studies have shown that HFDP has a positive impact on immune function. We first identified the active ingredients and targets of HFDP from the Traditional Chinese Medicine Systems Pharmacology database and the Swiss Target Prediction database, respectively. Next, we retrieved the differentially expressed genes (DEGs) related to immunity from the GEO databases. The intersection targets of the drugs and diseases were then analyzed using the STRING database for protein-protein interaction (PPI) network analysis, and the core targets were determined through topological analysis. Finally, the intersection genes were further analyzed using the DAVID database for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses. Subsequently, by analyzing the expression and prognostic survival of 12 core targets, 5 core target genes were identified, and molecular docking between the hub genes and immunity was performed. Finally, we used the CIBERSORT algorithm to analyze the immune infiltration of immunity genes In this study, 34 effective ingredients of HFDP, 530 target genes, and 568 differential genes were identified. GO and KEGG analysis showed that the intersection genes of HFDP targets and immunity-related genes were mainly related to complement and coagulation cascades, cytokine receptors, and retinol metabolism pathways. The molecular docking results showed that the 5 core genes had obvious affinity for the active ingredients of HFDP, which could be used as potential targets to improve the immunity of HFDP. Our findings suggest that HFDP is characterized by "multiple components, multiple targets, and multiple pathways" in regulating immunity. It may play an essential role in regulating immunity by regulating the expression and polymorphism of the central target genes ESR1, JUN, CYP3A4, CYP2C9, and SERPINE1.
Subject(s)
Astragalus propinquus , Drugs, Chinese Herbal , Molecular Docking Simulation , Network Pharmacology , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Protein Interaction Maps/genetics , Humans , Wolfiporia/chemistry , Medicine, Chinese TraditionalABSTRACT
Adjuvants, as the essential component of vaccines, are crucial in enhancing the magnitude, breadth and durability of immune responses. Unfortunately, commonly used Alum adjuvants predominantly provoke humoral immune response, but fail to evoke cellular immune response, which is crucial for the prevention of various chronic infectious diseases and cancers. Thus, it is necessary to develop effective adjuvants to simultaneously induce humoral and cellular immune response. In this work, we obtained a water soluble polysaccharide isolated and purified from Poria cocos, named as PCP, and explored the possibility of PCP as a vaccine adjuvant. The PCP, with Mw of 20.112 kDa, primarily consisted of â6)-α-D-Galp-(1â, with a small amount of â3)-ß-D-Glcp-(1 â and â4)-ß-D-Glcp-(1â. Our results demonstrated that the PCP promoted the activation of dendritic cells (DCs) and macrophages in vitro. As the adjuvant to ovalbumin, the PCP facilitated the activation of DCs in lymph nodes, and evoked strong antibody response with a combination of Th1 and Th2 immune responses. Moreover, compared to Alum adjuvant, the PCP markedly induced a potent cellular response, especially the cytotoxic T lymphocytes response. Therefore, we confirmed that the PCP has great potential to be an available adjuvant for simultaneously inducing humoral and cellular immune responses.
Subject(s)
Adjuvants, Immunologic , Dendritic Cells , Polysaccharides , Solubility , Water , Animals , Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/chemistry , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Mice , Water/chemistry , Dendritic Cells/drug effects , Dendritic Cells/immunology , Female , Macrophages/drug effects , Macrophages/immunology , Wolfiporia/chemistry , Ovalbumin/immunology , Immunity, Cellular/drug effects , Immunity, Humoral/drug effects , Poria/chemistryABSTRACT
PCP-W1, the Poria cocos polysaccharide with the strong immunomodulatory activity, was isolated through column chromatography and screened for in vitro immune activity in RAW 264.7 cells in this study. The structure analysis results revealed that the PCP-W1 were composed of galactose, glucose, fucose and mannose in a molar percentage of 35.87: 28.56: 21.77: 13.64. And it exhibited a random coil and branched conformational features with a molecular weight of 18.38 kDa. The main chain consisted of residuesâ3)-ß-D-Glcp-(1 â 3,6)-ß-D-Glcp-(1 â 3)-ß-D-Glcp-(1 â 6)-ß-D-Glcp-(1 â 6)-α-D-Galp-(1 â 6)-α-D-Galp-(1 â 2,6)-α-D-Galp-(1â6)-α-D-Galp-(1 â 6)-α-D-Galp-(1 â , while branching occurred at ß-D-Glcp-(1â, α-D-Manp-(1â, and α-L-Fucp-(1 â 3)- α-L-Fucp-(1â. The pharmacodynamic studies demonstrated that PCP-W1 activated the release of NO, IL-6, IL-ß, TNF-α, CD86, and ROS to induce polarization of RAW 264.7 murine macrophages towards M1-type through modulation of the TLR4/MD2/NF-κB pathway. The molecular docking results showed that PCP-W1 could primarily dock onto the hydrophobic binding site of TLR4/MD2 complex via its galactose chain. Furthermore, molecular dynamics simulation displayed stable modeling for TLR4-MD2-PCP-W1 complex. Overall, we screened the most immunoactive components of the polysaccharide, analyzed its structure, demonstrated its impact on TLR4/MD2/NF-kB pathway, and studied the interaction between TLR4/MD2 and the polysaccharide fragments. These results provide further support for the structure-activity relationship study of the immunomodulatory effects of Poria cocos polysaccharide.
Subject(s)
NF-kappa B , Polysaccharides , Signal Transduction , Toll-Like Receptor 4 , Wolfiporia , Animals , Mice , Toll-Like Receptor 4/metabolism , RAW 264.7 Cells , NF-kappa B/metabolism , Polysaccharides/pharmacology , Polysaccharides/chemistry , Signal Transduction/drug effects , Wolfiporia/chemistry , Lymphocyte Antigen 96/metabolism , Lymphocyte Antigen 96/chemistry , Immunologic Factors/pharmacology , Immunologic Factors/chemistry , Molecular Docking SimulationABSTRACT
Hyperuricemia (HUA) is a disorder of uric acid metabolism, which can lead to the formation of gouty arthritis, kidney inflammation and other damages. Previous studies have found that the alcohol extract of Poria cutis can reduce the level of uric acid and protect against kidney injury. Based on network pharmacology, the core targets and main active components of P. cutis intervention in HUA were determined. Most of the potential active ingredients are triterpenoid acids such as tumulosic acid (TA) and eburicoic acid (EA), and the potential targets are TNF and IL-6, which are associated with inflammation. In vitro experiments have shown that TA can significantly inhibit the release of NO, TNF-α and IL-6 in inflammatory RAW264.7 cell culture medium and the expression of TNF-α and IL-6 in RAW264.7 cells. This study suggests that TA based on network pharmacological screening has obvious anti-inflammatory effect on inflammatory RAW264.7 cells and is a promising anti-inflammatory compound.
Subject(s)
Anti-Inflammatory Agents , Interleukin-6 , Network Pharmacology , Nitric Oxide , Tumor Necrosis Factor-alpha , Wolfiporia , Animals , Mice , Anti-Inflammatory Agents/pharmacology , Interleukin-6/metabolism , RAW 264.7 Cells , Wolfiporia/chemistry , Tumor Necrosis Factor-alpha/metabolism , Nitric Oxide/metabolism , Triterpenes/pharmacology , Hyperuricemia/drug therapy , Inflammation/drug therapy , Inflammation/pathology , Cell LineABSTRACT
Poria cocos (Schw.) Wolf (PCW) are the dried sclerotia of Poaceae fungus Poria cocos that contain many biological activity ingredients such as polysaccharides and triterpenoids. The carbohydrates from Poria cocos have been proven to possess anti-inflammatory and antioxidant effects. This study aimed to investigate the impact and mechanism of Poria cocos oligosaccharides (PCO) protecting mice against acute lung injury (ALI). We examined the histopathological analysis of lung injury, inflammatory, and edema levels to evaluate the benefits of PCO during ALI. As a result, PCO improved the lipopolysaccharide (LPS) induced lung injury and decreased the inflammatory cytokines of lung tissue. Simultaneously, PCO alleviated lung edema by regulating the expression of aquaporin5 (AQP5) and epithelial Na+ channel protein (ENaC-α). Additionally, untargeted metabolomics was performed on the plasma of ALI mice via HUPLC-Triple-TOF/MS. The results indicated that linoleic acid, linolenic acid, arachidonic acid, carnosine, glutamic acid, and 1-methylhistamine were the biomarkers in ALI mice. Besides, metabolic pathway analysis suggested PCO affected the histidine and fatty acid metabolism, which were closely associated with inflammation and oxidative reaction of the host. Consequently, the effects of PCO inhibiting inflammation and edema might relate to the reducing pro-inflammatory mediators and the reverse of abnormal metabolic pathways.
Subject(s)
Acute Lung Injury , Lipopolysaccharides , Metabolomics , Oligosaccharides , Wolfiporia , Animals , Acute Lung Injury/chemically induced , Acute Lung Injury/metabolism , Acute Lung Injury/drug therapy , Mice , Metabolomics/methods , Lipopolysaccharides/toxicity , Oligosaccharides/pharmacology , Male , Wolfiporia/chemistry , Anti-Inflammatory Agents/pharmacology , Biomarkers/blood , Disease Models, Animal , Cytokines/metabolism , Lung/drug effects , Lung/metabolism , Lung/pathology , Inflammation/drug therapy , Inflammation/metabolism , Antioxidants/pharmacologyABSTRACT
We characterized the therapeutic biological modes of action of several terpenes in Poria cocos F.A Wolf (PC) and proposed a broad therapeutic mode of action for PC. Molecular docking and drug-induced transcriptome analysis were performed to confirm the pharmacological mechanism of PC terpene, and a new analysis method, namely diffusion network analysis, was proposed to verify the mechanism of action against Alzheimer's disease. We confirmed that the compound that exists only in PC has a unique mechanism through statistical-based docking analysis. Also, docking and transcriptomic analysis results could reflect results in clinical practice when used complementarily. The detailed pharmacological mechanism of PC was confirmed by constructing and analyzing the Alzheimer's disease diffusion network, and the antioxidant activity based on microglial cells was verified. In this study, we used two bioinformatics approaches to reveal PC's broad mode of action while also using diffusion networks to identify its detailed pharmacological mechanisms of action. The results of this study provide evidence that future pharmacological mechanism analysis should simultaneously consider complementary docking and transcriptomics and suggest diffusion network analysis, a new method to derive pharmacological mechanisms based on natural complex compounds.
Subject(s)
Molecular Docking Simulation , Terpenes , Transcriptome , Terpenes/pharmacology , Terpenes/chemistry , Transcriptome/drug effects , Humans , Wolfiporia/chemistry , Gene Expression Profiling/methods , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Alzheimer Disease/genetics , Microglia/drug effects , Microglia/metabolism , Antioxidants/pharmacology , Antioxidants/chemistry , Computational Biology/methods , AnimalsABSTRACT
Ulcerative colitis (UC), as a chronic inflammatory disease, presents a global public health threat. However, the mechanism of Poria cocos (PC) in treating UC remains unclear. Here, LC-MS/MS was carried out to identify the components of PC. The protective effect of PC against UC was evaluated by disease activity index (DAI), colon length and histological analysis in dextran sulfate sodium (DSS)-induced UC mice. ELISA, qPCR, and Western blot tests were conducted to assess the inflammatory state. Western blotting and immunohistochemistry techniques were employed to evaluate the expression of tight junction proteins. The sequencing of 16S rRNA was utilized for the analysis of gut microbiota regulation. The results showed that a total of fifty-two nutrients and active components were identified in PC. After treatment, PC significantly alleviated UC-associated symptoms including body weight loss, shortened colon, an increase in DAI score, histopathologic lesions. PC also reduced the levels of inflammatory cytokines TNF-α, IL-6, and IL-1ß, as evidenced by the suppressed NF-κB pathway, restored the tight junction proteins ZO-1 and Claudin-1 in the colon, and promoted the diversity and abundance of beneficial gut microbiota. Collectively, these findings suggest that PC ameliorates colitis symptoms through the reduction in NF-κB signaling activation to mitigate inflammatory damage, thus repairing the intestinal barrier, and regulating the gut microbiota.
Subject(s)
Colitis, Ulcerative , Dextran Sulfate , Gastrointestinal Microbiome , NF-kappa B , Signal Transduction , Wolfiporia , Animals , Gastrointestinal Microbiome/drug effects , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/metabolism , Colitis, Ulcerative/microbiology , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , NF-kappa B/metabolism , Mice , Signal Transduction/drug effects , Wolfiporia/chemistry , Male , Disease Models, Animal , Cytokines/metabolism , Colon/pathology , Colon/metabolism , Colon/drug effects , Colon/microbiology , Tight Junction Proteins/metabolism , Mice, Inbred C57BLABSTRACT
To reduce pollution caused by traditional plastic packaging and preparation of silver nanoparticles (AgNPs), this work aims to develop biological macromolecular packaging films with green synthesized AgNPs. In this study, a novel P. cocos polysaccharide (PCP) with a unique monosaccharide composition was extracted from Poria cocos (Schw.) Wolf. Then, this polysaccharide containing 24.68 % rhamnose was used as a stabilizer for the green synthesis of PCP-AgNPs for the first time. PCP-AgNPs exhibited excellent antibacterial activity against P. aeruginosa, E. coli, and S. aureus, with the highest antibacterial activity against E. coli (inhibition zone diameter = 11.14 ± 0.79 mm). Subsequently, PCP-AgNPs/chitosan (CS) film was successfully prepared by incorporating PCP-AgNPs into the CS film solution. Several experiments demonstrated that the addition of this nanomaterial promoted the formation of noncovalent interactions between CS and PCP-AgNPs, resulting in a more regular and denser film. Compared to the CS film and control group, the PCP-AgNPs/CS film significantly maintained the quality indexes of strawberries. Therefore, this composite film successfully extended the shelf life of strawberries. Regarding safety, these packaging films were not cytotoxic toward RAW264.7 cells. In conclusion, the environmentally friendly PCP-AgNPs/CS film has the potential to replace some traditional food packaging materials.
Subject(s)
Anti-Bacterial Agents , Food Packaging , Green Chemistry Technology , Metal Nanoparticles , Polysaccharides , Silver , Metal Nanoparticles/chemistry , Silver/chemistry , Food Packaging/methods , Polysaccharides/chemistry , Polysaccharides/pharmacology , Mice , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Animals , RAW 264.7 Cells , Wolfiporia/chemistry , Microbial Sensitivity Tests , Escherichia coli/drug effectsABSTRACT
The active ingredient in Poria cocos, a parasitic plant belonging to the family Polyporaceae, is Poria cocos polysaccharide (PCP). PCP exhibits liver protection and anti-inflammatory effects, although its effect on alcoholic liver disease (ALD) remains unstudied. This study investigated the mechanism of PCP in improving ALD by regulating the Nrf2 signaling pathway. After daily intragastric administration of high-grade liquor for 4 hours, each drug group received PCPs or the ferroptosis inhibitor ferrostatin-1. The Nrf2 inhibitor ML385 (100 mg/kg/day) group was intraperitoneally injected, after which PCP (100 mg/kg/day) was administered by gavage. Samples were collected after 6 weeks for liver function and blood lipid analysis using an automatic biochemical analyzer. In the alcoholic liver injury cell model established with 150 mM alcohol, the drug group was pretreated with PCP, Fer-1, and ML385, and subsequent results were analyzed. The results revealed that PCP intervention significantly reduced liver function and blood lipid levels in alcohol-fed rats, along with decreased lipid deposition. PCP notably enhanced Nrf2 signaling expression, regulated oxidative stress levels, inhibited NF-κß, and its downstream inflammatory signaling pathways. Furthermore, PCP upregulated FTH1 protein expression and reduced intracellular Fe2+, suggesting an improvement in ferroptosis. In vitro studies yielded similar results, indicating that PCP can reduce intracellular ferroptosis by regulating oxidative stress and improve alcoholic liver injury by inhibiting the production of inflammatory factors.
Subject(s)
Ferroptosis , Liver Diseases, Alcoholic , NF-E2-Related Factor 2 , Polysaccharides , Animals , Liver Diseases, Alcoholic/metabolism , Liver Diseases, Alcoholic/drug therapy , Ferroptosis/drug effects , NF-E2-Related Factor 2/metabolism , Polysaccharides/pharmacology , Rats , Male , Signal Transduction/drug effects , Oxidative Stress/drug effects , Humans , Rats, Sprague-Dawley , Liver/metabolism , Liver/drug effects , Liver/pathology , Wolfiporia/chemistry , Disease Models, AnimalABSTRACT
In order to investigate the structural characteristics and immunomodulatory effects of Poria cocos polysaccharides, a water-soluble homogeneous polysaccharide (PCP-2) was isolated by water extraction and alcohol precipitation and further purified by Cellulose DEAE-52 and Sephacryl S-100HR column chromatography. PCP-2 is a heteropolysaccharide composed of glucose, galactose, mannose, and fucose in a molar ratio of 42.0: 35.0: 13.9: 9.1. It exhibits a narrow molecular weight distribution at 2.35 kDa with a branching degree of 37.1 %. The main chain types of PCP-2 include 1,3-ß-D-Glc and 1,6-ß-D-Glc as the backbone glucans and 1,6-α-D-Gal as the backbone heterogalactan. In vitro experiments demonstrate that PCP-2 directly stimulate RAW264.7 cell proliferation and secretion of inflammatory factors such as NO and TNF-α. In cyclophosphamide (CTX)-induced mice, it promotes the development of thymus and spleen immune organs, elevates the blood levels of IgG, IgA, IgM and CD3+CD4+ T cells, increases the intestinal villus height/ crypt depth ratio and improves gut barrier dysfunctions. These findings suggest that PCP-2 is a natural fungal polysaccharide with broad spectrum of immunoenhancing effects, which can significantly ameliorate the immunocompromised state.
Subject(s)
Fungal Polysaccharides , Poria , Wolfiporia , Mice , Animals , Wolfiporia/chemistry , Water , Polysaccharides/chemistry , Fungal Polysaccharides/pharmacology , Fungal Polysaccharides/chemistry , Tumor Necrosis Factor-alpha , Poria/chemistryABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic ulcers represent a chronic condition characterized by prolonged hyperglycemia and delayed wound healing, accompanied by endocrine disorders, inflammatory responses, and microvascular damage in the epidermal tissue, demanding effective clinical treatment approaches. For thousands of years, ancient Chinese ethnopharmacological studies have documented the use of Poria cocos (Schw.) Wolf in treating diabetic ulcers. Recent research has substantiated the diverse pharmacological effects of Poria cocos (Schw.) Wolf, including its potential to alleviate hyperglycemia and exhibit anti-inflammatory, antioxidant, and immune regulatory properties, which could effectively mitigate diabetic ulcer symptoms. Furthermore, being a natural medicine, Poria cocos (Schw.) Wolf has demonstrated promising therapeutic effects and safety in the management of diabetic ulcers, holding significant clinical value. Despite its potential clinical efficacy and applications in diabetic ulcer treatment, the primary active components and underlying pharmacological mechanisms of Poria cocos (Schw.) Wolf remains unclear. Further investigations are imperative to establish a solid foundation for drug development in this domain. AIM OF THE STUDY AND MATERIALS AND METHODS: In this study, we aimed to identify the active compounds and potential targets of Poria cocos (Schw.) Wolf using UHPLC-Q-TOF-MS and TCMSP databases. Additionally, we attempt to identify targets related to diabetic ulcers. Following enrichment analysis, a network of protein-protein interactions was constructed to identify hub genes based on the common elements between the two datasets. To gain insights into the binding activities of the hub genes and active ingredients, molecular docking analysis was employed. Furthermore, to further validate the therapeutic effect of Poria cocos (Schw.) Wolf, we exerted in vitro experiments using human umbilical vein vascular endothelial cells and human myeloid leukemia monocytes (THP-1). The active ingredient of Poria cocos (Schw.) Wolf was applied in these experiments. Our investigations included various assays, such as CCK-8, scratch test, immunofluorescence, western blotting, RT-PCR, and flow cytometry, to explore the potential of Poria cocos (Schw.) Wolf triterpenoid extract (PTE) in treating diabetic ulcers. RESULTS: The findings here highlighted PTE as the primary active ingredient in Poria cocos (Schw.) Wolf. Utilizing network pharmacology, we identified 74 potential targets associated with diabetic ulcer treatment for Poria cocos (Schw.) Wolf, with five hub genes (JUN, MAPK1, STAT3, AKT1, and CTNNB1). Enrichment analysis revealed the involvement of multiple pathways in the therapeutic process, with the PI3K-AKT signaling pathway showing significant enrichment. Through molecular docking, we discovered that relevant targets within this pathway exhibited strong binding with the active components of Poria cocos (Schw.) Wolf. In vitro experiments unveiled that PTE (10 mg/L) facilitated the migration of human umbilical vein vascular endothelial cells (P < 0.05). PTE also increased the expression of CD31 and VEGF mRNA (P < 0.05) while activating the expressions of p-PI3K and p-AKT (P < 0.05). Moreover, PTE demonstrated its potential by reducing the expression of IL-1ß, IL-6, TNF-α, and NF-κB mRNA in THP-1 (P < 0.05) and fostering M2 macrophage polarization. These results signify the potential therapeutic effects of PTE in treating diabetic ulcers, with its beneficial actions mediated through the PI3K-AKT signaling pathway. CONCLUSIONS: PTE is the main active ingredient in Poria cocos (Schw.) Wolf that exerts therapeutic effects. Through PI3K-AKT signaling pathway activation and inflammatory response reduction, PTE promotes angiogenesis, thereby healing diabetic ulcers.
Subject(s)
Antineoplastic Agents , Diabetes Mellitus , Drugs, Chinese Herbal , Hyperglycemia , Triterpenes , Wolfiporia , Wolves , Animals , Humans , Proto-Oncogene Proteins c-akt , Wolfiporia/chemistry , Phosphatidylinositol 3-Kinases , Ulcer , Molecular Docking Simulation , Endothelial Cells , Signal Transduction , Antineoplastic Agents/pharmacology , Triterpenes/pharmacology , Triterpenes/therapeutic use , Triterpenes/analysis , RNA, Messenger , Diabetes Mellitus/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic useABSTRACT
Poria cocos (Schw.) Wolf (P. cocos) has been widely used as medical plant in East Asia with remarkable anti-Alzheimer's disease (anti-AD) activity. However, the underlying mechanisms are still confused. In this study, based on the ß-Amyloid deposition hypothesis of AD, an integrated analysis was conducted to screen and separation 5-lipoxygenase (5-LOX) inhibitors from triterpenoids of P. cocos and investigate the anti-AD mechanisms, containing bioaffinity ultrafiltration UPLC-Q-Exactive, molecular docking, and multiple complex networks. Five triterpenoids were identified as potential 5-LOX inhibitors, including Tumulosic acid, Polyporenic acid C, 3-Epi-dehydrotumulosic acid, Pachymic acid and Dehydrotrametenolic acid. Five potential 5-LOX inhibitors were screened by ultrafiltration affinity assay in P. cocos. The molecular docking simulation results are consistent with the ultrafiltration experimental results, which further verifies the accuracy of the experiment. The commercial 5-LOX inhibitor that Zileuton was used as a positive control to evaluate the inhibitory effect of active ingredients on 5-LOX. Subsequently, the established separation method allowed the five active ingredients (Pachymic acid, 3-Epi-dehydrotumulosic acid, Dehydrotrametenolic acid, Tumulosic acid and Polyporenic acid C) with high purity to be isolated. Targeting network pharmacology analysis showed that five active ingredients correspond to a total of 286 targets. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis found that target cells were mainly enriched in Pathways in cancer, Lipid and atherosclerosis. Our results indicate that P. cocos extract has the potential to be used in the prevention and treatment of neurodegenerative diseases. This will help elucidate the mechanisms of action of various medicinal plants at the molecular level and provide more opportunities for the discovery and development of new potential treatments from health food resources.
Subject(s)
Lipoxygenase Inhibitors , Molecular Docking Simulation , Triterpenes , Wolfiporia , Triterpenes/pharmacology , Triterpenes/isolation & purification , Triterpenes/chemistry , Lipoxygenase Inhibitors/pharmacology , Lipoxygenase Inhibitors/isolation & purification , Wolfiporia/chemistry , Molecular Structure , Ultrafiltration , Arachidonate 5-Lipoxygenase/metabolism , Chromatography, High Pressure Liquid , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Plants, Medicinal/chemistry , Network PharmacologyABSTRACT
Poria cocos is a popular medicinal food. Polysaccharides are the key component of Poria cocos, forming 70-90 % of the dry sclerotia mass. Recent studies indicate that Poria cocos polysaccharides (PCP-Cs) have multiple beneficial functions and applications. A literature search was conducted using the Web of Science Core Collection and PubMed databases. For this review, we provided an updated research progress in chemical structures, various extraction and analysis technologies, bioactivities of PCP-Cs, and insights into the directions for future research. The main polysaccharides identified in Poria cocos are water-soluble polysaccharides and acidic polysaccharides. Hot water, alkali, supercritical fluid, ultrasonic, enzyme, and deep eutectic solvent-based methods are the most common methods for PCP-Cs extraction. Technologies such as near-infrared spectroscopy, high-performance liquid chromatography, and ultraviolet-visible spectrophotometry, are commonly used to evaluate the qualities of PCP-Cs. In addition, PCP-Cs have antioxidant, immunomodulatory, neuroregulatory, anticancer, hepatoprotective, and gut microbiota regulatory properties. Future research is needed to focus on scaling up extraction, enhancing quality control, elucidating mechanisms of bioactivities, and the utilisation of PCP-Cs in food industries. Overall, Poria cocos is a good source of edible fungi polysaccharides, which can be developed into functional foods with potential health benefits.
Subject(s)
Fungal Polysaccharides , Poria , Wolfiporia , Fungal Polysaccharides/pharmacology , Fungal Polysaccharides/chemistry , Wolfiporia/chemistry , Polysaccharides/pharmacology , Polysaccharides/chemistry , Water , Quality Control , Poria/chemistryABSTRACT
Neurogenesis in the adult brain comprises the entire set of events of neuronal development. It begins with the division of precursor cells to form a mature, integrated, and functioning neuronal network. Adult neurogenesis is believed to play an important role in animals' cognitive abilities, including learning and memory. In the present study, significant neuronal differentiation-promoting activity of 80% (v/v) ethanol extract of P. cocos (EEPC) was found in Neuro-2a cells and mouse cortical neural stem/progenitor cells (NSPCs). Subsequently, a total of 97 compounds in EEPC were identified by UHPLC-Q-Exactive-MS/MS. Among them, four major compounds-Adenosine; Choline; Ethyl palmitoleate; and L-(-)-arabinitol-were further studied for their neuronal differentiation-promoting activity. Of which, choline has the most significant neuronal differentiation-promoting activity, indicating that choline, as the main bioactive compound in P. cocos, may have a positive effect on learning and memory functions. Compared with similar research literature, this is the first time that the neuronal differentiation-promoting effects of P. cocos extract have been studied.
Subject(s)
Biological Products , Neurons , Wolfiporia , Animals , Mice , Cell Differentiation , Choline , Ethanol , Neurons/drug effects , Stem Cells , Tandem Mass Spectrometry , Wolfiporia/chemistry , Biological Products/pharmacologyABSTRACT
The optimal cultivation conditions and chemical components of Poria cocos fruiting bodies were examined by employing the single factor and response surface methods to screen for optimal conditions for artificial cultivation. The differences in chemical composition among the fruiting bodies, fermented mycelium, and sclerotia of P. cocos were compared using UV spectrophotometry and high-performance liquid chromatography (HPLC). The optimal growth conditions for P. cocos fruiting bodies were 28.5°C temperature, 60% light intensity, and 2.5 g pine sawdust, which resulted in the production of numerous basidiocarps and basidiospores under microscopic examination. Polysaccharides, triterpenoids, and other main active components of P. cocos were found in the fruiting bodies, sclerotia, and fermented mycelium. The triterpenoid components of the fruiting bodies were consistent with those of the sclerotia. The content of pachymic acid in the fruiting bodies was significantly higher than that in the sclerotia, with a value of 33.37 ± 0.1902 mg/g. These findings provide novel insights into the sexual breeding and comprehensive development and utilization of P. cocos.
Subject(s)
Wolfiporia , Wolfiporia/chemistry , Chromatography, Gas , Mycelium/chemistry , Chromatography, High Pressure Liquid , Fruiting Bodies, FungalABSTRACT
Most reported polysaccharides from Poria cocos (PCPs) in traditional Chinese medicine decoctions were water-soluble heteropolysaccharides while the water-insoluble PCPs were scarcely researched due to the poor water-solubility. In this study, a water-insoluble polysaccharide with high yield of 59%, and high purity with a glucan content of 98.8%, was isolated by diluted sodium hydroxide at low temperature and coded as PCPA. The chemical structure of PCPA was identified as a liner ß-glucan with 1, 3-linked glycosidic bond by the fourier infrared spectrum (FT-IR), ion chromatography (ICP), gas chromatography and mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) measurements. Importantly, PCPA was successfully used to construct hydrogels (PCPA-Gs) with good thermal stability, water retention ability and swelling property through simple physical cross-linking, due to the abundance of hydroxyl groups on glucan chains. Moreover, the rheology analysis of PCPA-Gs showed a rapid transition between gel and sol as well as the shear-thinning property. The hydrogel developed in this study holds promise for applications in the food, pharmaceutical, and cosmetic fields.
Subject(s)
Wolfiporia , beta-Glucans , Wolfiporia/chemistry , Water , Hydrogels , Spectroscopy, Fourier Transform Infrared , Polysaccharides/chemistryABSTRACT
This study compares the bioactivity of six sulfated polysaccharides derived from glucose- and sucrose-feeding extracted from P. cocos. Anti-inflammatory potentials of these polysaccharides were evaluated by pretreating lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. Of the tested polysaccharides, the sulfated polysaccharide derived from sucrose-feeding at the concentration of 40 g/l (referred to as "suc 40") exhibited the highest anti-inflammatory activity, of 83 %, and 33 % inhibition of IL-6 and TNF-α secretion, respetively. It achieved this by inhibiting the p-38 and c-Jun N-terminal kinase (JNK) MAPK signaling pathways. On the other hand, the sulfated polysaccharide derived from glucose-feeding at a concentration of 20 g/l (referred to as "glc 20") demonstrated the greatest anti-lung cancer activity. This was achieved by inducing apoptotic-related molecules, such as poly (ADP-ribose) polymerase (PARP) and CHOP. Furthermore, glc 20 had the highest contents of sulfate, fucose, and mannose compared to the other tested polysaccharides. This suggests that the composition of monosaccharide residues are critical factors influencing the anti-inflammatory and anti-cancer activities of these sulfated polysaccharides. Overall, this study highlights the potential of sulfated polysaccharides derived from P. cocos to function as bioactive compounds with anti-inflammatory and anti-cancer properties.
Subject(s)
Neoplasms , Wolfiporia , Humans , Wolfiporia/chemistry , Sulfates/therapeutic use , Polysaccharides/chemistry , Anti-Inflammatory Agents/chemistry , Neoplasms/drug therapy , Sucrose , GlucoseABSTRACT
The function of the intestinal tract is critical to human health. Poria cocos is a widely used functional edible fungus in Asia and has been reported to modulate gastrointestinal function. However, the effects of polysaccharides, the main active constituents of Poria cocos, on the intestinal tract remains unclear and is the focus of the study. Poria cocos polysaccharides (PCP) were extracted, characterized, and administered to mice by gavage. The results show that PCP used in this study has a typical polysaccharide peak with a molecular weight of 11.583 kDa and is composed primarily of mannose, D-glucosamine hydrochloride, glucose, galactose, and fucose with a molar ratio of 15.308: 0.967: 28.723: 31.631: 23.371. The methylation results suggest that the PCP backbone may be t-Gal(p), 6-Gal(p) and 2,6-Gal(p). The effects of PCP on the mucosal barrier function of the mouse intestine (duodenum, jejunum, and ileum) were examined in terms of intestinal physiological status, physical barrier, biochemical barrier, immune barrier, and microbial barrier. The results showed that PCP significantly improved the physiological state of mouse intestine. Moreover, PCP strengthened the intestinal physical barrier by upregulating the expression of intestinal Occludin and ZO-1 and downregulating the levels of serum endotoxin, DAO, D-lactate, and intestinal MPO. Regarding biochemical barrier, PCP could upregulate the expression of MUC2, ß-defensin, and SIgA in intestinal tissues. In addition, PCP modulated the immune barrier by increasing IL-2, IL-4, IL-6, IL-10, TGF-ß, and IFN-γ expression. Besides, PCP increased the level of SCFAs in small intestinal contents. PCP modulates intestinal barrier function by altering the microbial composition of the gut. We also found that PCP could maintain intestinal barrier function by increasing the expression of Wnt/ß-Catenin and Lrp5 proteins. Generally, our findings suggested that PCP may be used as a functional food to regulate intestinal mucosal function, thereby enhancing the health of the intestinal and host.
Subject(s)
Poria , Wolfiporia , Humans , Animals , Mice , Wolfiporia/chemistry , Polysaccharides/pharmacology , Polysaccharides/chemistry , Antioxidants/pharmacology , Poria/chemistryABSTRACT
The edible values of P. cocos from different origins vary significantly, therefore, it is important to investigate the traceability of geographical regions and identify the geographical biomarkers of P. cocos. The metabolites of P. cocos of the different geographical origins were assessed using liquid chromatography tandem-mass spectrometry, principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA). The OPLS-DA could clearly discriminate the metabolites of P. cocos from the three cultivation regions (YN, Yunnan; AH, Anhui; JZ, Hunan). Finally, three carbohydrates, four amino acids, and four triterpenoids were selected as biomarkers for P. cocos origin tracing. Correlation matrix analysis revealed that the contents of biomarkers were closely related to geographical origin. Altitude, temperature, and soil fertility were the main factors responsible for the differences in biomarker profiles in P. cocos. The metabolomics approach provides an effective strategy for tracing and identifying the biomarkers of P. cocos from different geographical origins.