Structure characteristics, protective effect and mechanisms of ethanol-fractional polysaccharides from Dendrobium officinale on acute ethanol-induced gastritis.

Gastritis is a common disease characterized by gastric ulcers and severe bleeding. Excessive daily alcohol consumption can cause acute gastritis, impacting individuals' quality of life. This study aims to explore the protective effects of different ethanol-fractional polysaccharides of Dendrobium officinale (EPDO) on acute alcohol-induced gastric injury in vivo. Results showed that EPDO-80, identified as a ß-glucan, exhibited significant anti-inflammatory properties in pathology. It could reduce the area of gastric mucosal injury and cell infiltration. EPDO-80 had a dose-effect relationship in reducing the levels of malondialdehyde and cyclooxygenase-2 and decreasing the levels of inflammation mediators such as tumor necrosis factor α. More extensively, EPDO-80 could inhibit the activation of the TNFR/IκB/NF-κB signaling pathway, reducing the production of TNF-α mRNA and cell apoptosis in organs. Conversely, EPDO-80 could promote changes in the gut microbiota structure. These findings suggest that EPDO-80 could have great potential in limiting oxidative stress and inflammation mediated by inhibiting the NF-κB signaling pathway, which is highly related to its ß-glucan structure and functions in gut microbiota.

Dendrobium officinale regulate lipid metabolism in diabetic mouse liver via PPAR-RXR signaling pathway: Evidence from an integrated multi-omics analysis.

Dendrobium officinale (DEN) is recognized as a kind of functional food that can effectively ameliorate endocrine and metabolic disruptions. This study delved into the pharmacological mechanism of DEN on hepatic lipotoxicity associated with Type II diabetes mellitus (T2DM). In vivo study experiments on db/db mice indicated that DEN treatment notably enhanced liver function, decreased blood lipid levels, and improved insulin sensitivity. Non-targeted metabolomics analysis revealed that DEN significantly ameliorated metabolism pathways, including lipoic acid, linoleic acid, bile secretion, and the alanine/aspartate/glutamate metabolism, as well as taurine and hypotaurine metabolism. Transcriptomics analysis demonstrated DEN treatment could modulate the expression of genes such as Cpt1b, Scd1, G6pc2, Fos, Adrb2, Atp2a1, Ppp1r1b, and Cyp7a1. Furthermore, Proteomics analysis indicated that the beneficial effect of DEN on lipid metabolism was linked to pathways like AMPK and PPAR signaling. The integrative analysis of multi-omics revealed that the PPAR-RXR signaling was critical to the therapeutic effect of DEN on T2DM-induced fatty liver. Additionally, in vitro study on AML-12 cells confirmed that DEN counteract PA-induced lipid accumulation by activating the PPAR-RXR pathway. Overall, these findings suggested that DEN exhibited the potential to mitigate T2DM-induced hepatic lipo-toxicity and manage lipid imbalances in T2DM.

Effects of Ethanol Concentrations on Primary Structural and Bioactive Characteristics of Dendrobium officinale Polysaccharides.

Ethanol fractional precipitation can initially separate polysaccharides according to the structure, which exhibits strong correlation with the biological activities. This study aimed to investigate the impact of varying ethanol concentrations on the structural characteristics, and the antitumor and antioxidant activities of polysaccharides derived from Dendrobium officinale through ethanol fractional precipitation, as well as their internal relationships. The polysaccharides acquired by absolute alcohol additions at a final liquor-ethanol volume ratio of 1:1, 1:2, and 1:4 were named DOP-1, DOP-2, and DOP-4, and the supernatant was named DOP-S. The results of the structural analysis revealed that the increase in ethanol concentrations resulted in a reduction in the molecular weights and the acetylation degree of the polysaccharides, as well as a decrease in mannose content and an increase in glucose content. In vitro experiments demonstrated that DOP-S exhibited optimal antitumor and antioxidant activities. Animal experiments further confirmed that DOP-S suppressed the growth of solid tumors significantly, enhanced lymphocytes, mediated immune ability, and improved the activity of antioxidant enzymes. These findings would establish a theoretical foundation and provide technical support for further advances and applications of polysaccharides derived from D. officinale in the fields of food and medicine.

Integrated component identification, network pharmacology, and experimental verification revealed mechanism of Dendrobium officinale Kimura et Migo against lung cancer.

BACKGROUND: Dendrobium officinale Kimura et Migo (DO), a valuable Chinese herbal medicine, has been reported to exhibit potential effects in the prevention and treatment of lung cancer. However, its material basis and mechanism of action have not been comprehensively analyzed. PURPOSE: The objective of this study was to preliminarily elucidate the active components and pharmacological mechanisms of DO in treating lung cancer, according to UPLC-Q/TOF-MS, HPAEC-PAD, network pharmacology, molecular docking, and experimental verification. METHODS: The chemical components of DO were identified via UPLC-Q/TOF-MS, while the monosaccharide composition of Dendrobium officinale polysaccharide (DOP) was determined by HPAEC-PAD. The prospective active constituents of DO as well as their respective targets were predicted in the combined database of Swiss ADME and Swiss Target Prediction. Relevant disease targets for lung cancer were searched in OMIM, TTD, and Genecards databases. Further, the active compounds and potential core targets of DO against lung cancer were found by the C-T-D network and the PPI network, respectively. The core targets were then subjected to enrichment analysis in the Metascape database. The main active compounds were molecularly docked to the core targets and visualized. Finally, the viability of A549 cells and the relative quantity of associated proteins within the major signaling pathway were detected. RESULTS: 249 ingredients were identified from DO, including 39 flavonoids, 39 bibenzyls, 50 organic acids, 8 phenanthrenes, 27 phenylpropanoids, 17 alkaloids, 17 amino acids and their derivatives, 7 monosaccharides, and 45 others. Here, 50 main active compounds with high degree values were attained through the C-T-D network, mainly consisting of bibenzyls and monosaccharides. Based on the PPI network analysis, 10 core targets were further predicted, including HSP90AA1, SRC, ESR1, CREBBP, MAPK3, AKT1, PIK3R1, PIK3CA, HIF1A, and HDAC1. The results of the enrichment analysis and molecular docking indicated a close association between the therapeutic mechanism of DO and the PI3K-Akt signaling pathway. It was confirmed that the bibenzyl extract and erianin could inhibit the multiplication of A549 cells in vitro. Furthermore, erianin was found to down-regulate the relative expressions of p-AKT and p-PI3K proteins within the PI3K-Akt signaling pathway. CONCLUSIONS: This study predicted that DO could treat lung cancer through various components, multiple targets, and diverse pathways. Bibenzyls from DO might exert anti-lung cancer activity by inhibiting cancer cell proliferation and modulating the PI3K-Akt signaling pathway. A fundamental reference for further studies and clinical therapy was given by the above data.

Dendrobium officinale Polysaccharide (DOP) inhibits cell hyperproliferation, inflammation and oxidative stress to improve keratinocyte psoriasis-like state.

PURPOSE: Psoriasis is a skin disease characterized by excessive proliferation, inflammation and oxidative stress in keratinocytes. The present study aimed to investigate the therapeutic effects of Dendrobium officinale polysaccharide (DOP) on keratinocyte psoriasis-like models. METHODS: The HaCaT keratinocyte inflammation models were induced by interleukin (IL)-22 or lipopolysaccharide (LPS), respectively, and oxidative stress damage within cells was elicited by H2O2 and treated using DOP. CCK-8 and EdU were carried out to detect cell proliferation. ELISA, qRT-PCR, and Western blot were conducted to measure the expression of pro-inflammatory cytokines IL17A, IL-23, IL1ß, tumor necrosis factor alpha (TNF-α), and IL-6. Reactive oxygen species (ROS) level in keratinocytes was detected by flow cytometry. Cell proliferation-associated proteins (PCNA, Ki67, Cyclin D1) and pathway proteins (p-AKT and AKT), and oxidative stress marker proteins (Nrf-2, CAT, SOD1) were detected by Western blot. RESULT: DOP did not affect the proliferation of normal keratinocytes, but DOP was able to inhibit the proliferative activity of IL-22-induced overproliferating keratinocytes and suppress the expression of proliferation-related factors PCNA, Ki67, and Cyclin D1 as well as the proliferation pathway p-AKT. In addition, DOP treatment was able to inhibit IL-22 and LPS-induced inflammation and H2O2-induced oxidative stress, including the expression of IL17A, IL-23, IL1ß, TNF-α, IL-6, and IL1ß, as well as the expression levels of intracellular ROS levels and cellular oxidative stress-related indicators SOD, MDA, CAT, Nrf-2 and SOD1. CONCLUSION: DOP inhibits keratinocyte hyperproliferation, inflammation and oxidative stress to improve the keratinocyte psoriasis-like state.

Material basis and core chemical structure of Dendrobium officinale polysaccharides against colitis-associated cancer based on anti-inflammatory activity.

It has been claimed that Dendrobium officinale polysaccharides (PSs) can degrade into oligosaccharide and then transform into short-chain fatty acids in the intestine after oral administration, and play an anti-colitis-associated cancer (CAC) effect by inhibiting intestinal inflammation. However, the material basis and core chemical structure underlying the anti-colon cancer properties of PSs have not yet been elucidated. In this study, PSs were degraded into enzymatic oligosaccharides (OSs) using ß-mannanase. The results of in vivo experiments revealed that PSs and OSs administered by gastric lavage had similar antitumor effects in CAC mice. OS-1 (Oligosaccharide compounds 1) and OS-2 (Oligosaccharide compounds 2) were further purified and characterized from OSs, and it was found that OS-1, OS-2, OSs, and PSs had similar and consistent anti-inflammatory activities in vitro. Chemical structure comparison and evaluation revealed that the chemical structure of ß-D-Manp-(1 â†’ 4)-ß-D-Glcp corresponding to OS-1 was the least common PS structure with anti-colitic activity. Therefore, our findings suggest that OSs are the material basis for PSs to exert anti-CAC activity and that the chemical structure of ß-D-Manp-(1 â†’ 4)-ß-D-Glcp corresponding to OS-1 is the core chemical structure of PSs against CAC.

Dendrobium officinale Polysaccharides as a Natural Functional Component for Acetic-Acid-Induced Gastric Ulcers in Rats.

Dendrobium officinale is an important edible and medicinal plant, with the Dendrobium officinale polysaccharide (DOP) being its primary active constituent, known for its diverse biological activities. In this study, DOP was extracted and characterized for its structural properties. The potential of DOP to ameliorate gastric ulcers (GUs) was investigated using an acetic-acid-induced GU model in rats. The results demonstrated that DOP exerted a multifaceted protective effect against GU, mitigating the deleterious impact on food intake and body weight in rats. DOP exhibited its protective action by attenuating cellular damage attributed to oxidative stress and inflammatory reactions mediated by enhanced activities of SOD, GSH, and GSH-PX, coupled with a downregulation in the expression of pro-inflammatory cytokines, including IL-1ß, IL-6, and TNF-α. Furthermore, DOP effectively inhibited apoptosis in gastric mucosa cells of acetic-acid-induced GU rat models and facilitated the self-repair of damaged tissues. Remarkably, the DOP-200 and DOP-400 groups outperformed omeprazole in reducing the expression of IL-6 and malondialdehyde (MDA) in tissues, as well as IL-1ß, IL-6, and TNF-α in serum. These groups also exhibited an improved expression of SOD in tissues and SOD, GSH, and GSH-PX in serum. A Western blot analysis of gastric mucosa demonstrated that the DOP-200 and DOP-400 groups significantly reduced the expression of NF-κBp65, phosphorylated NF-κBp65, FoxO3a, and Bim. The observed antagonism to GU appeared to be associated with the NF-κB cell pathway. Additionally, qRT-PCR results indicate that DOP reduced the mRNA transcription levels of IL-6, and TNF-α, which shows that the healing of GU is related to the reduction in the inflammatory reaction by DOP. However, the expression of EGF and VEGF decreased, suggesting that the mechanism of DOP inhibiting GU may not be directly related to EGF and VEGF, or there is an uncertain competitive relationship between them, so further research is needed.

Diverse modulatory effects of bibenzyls from Dendrobium species on human immune cell responses under inflammatory conditions.

Dendrobium plants are widely used in traditional Chinese medicine. Their secondary metabolites such as bibenzyls and phenanthrenes show various pharmacological benefits such as immunomodulation and inhibitory effects on cancer cell growth. However, our previous study also showed that some of these promising compounds (i.e., gigantol and cypripedin) also induced the expression of inflammatory cytokines including TNF in human monocytes, and thus raising concerns about the use of these compounds in clinical application. Furthermore, the effects of these compounds on other immune cell populations, apart from monocytes, remain to be investigated. In this study, we evaluated immunomodulatory effects of seven known bibenzyl compounds purified from Dendrobium species in human peripheral blood mononuclear cells (PBMCs) that were stimulated with lipopolysaccharide (LPS). Firstly, using flow cytometry, moscatilin (3) and crepidatin (4) showed the most promising dose-dependent immunomodulatory effects among all seven bibenzyls, determined by significant reduction of TNF expression in LPS-stimulated CD14+ monocytes. Only crepidatin at the concentration of 20 µM showed a significant cytotoxicity, i.e., an increased cell death in late apoptotic state. In addition, deep immune profiling using high-dimensional single-cell mass cytometry (CyTOF) revealed broad effects of Dendrobium compounds on diverse immune cell types. Our findings suggest that to precisely evaluate therapeutic as well as adverse effects of active natural compounds, a multi-parameter immune profiling targeting diverse immune cell population is required.

Dendrobium polysaccharide (DOP) ameliorates the LL-37-induced rosacea by inhibiting NF-κB activation in a mouse model.

BACKGROUND: Rosacea, a common chronic inflammatory skin disease worldwide, is currently incurable with complex pathogenesis. Dendrobium polysaccharide (DOP) may exert therapeutic effects on rosacea via acting on the NF-κB-related inflammatory and oxidative processes. MATERIALS AND METHODS: In this study, an LL-37-induced rosacea-like mouse model was established. HE staining was used to assess the skin lesions, erythema severity scores, pathological symptoms, and inflammatory cell numbers of mice in each group. The inflammation level was quantitatively analyzed using enzyme-linked immunosorbent assay (ELISA) and reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). The expression levels of TLR4 and p-NF-κB were finally detected. RESULTS: DOP improved skin pathological symptoms of rosacea mice. DOP also alleviated the inflammation of rosacea mice. Moreover, the TLR4/NF-κB pathway was observed to be inhibited in the skin of mice after DOP application. These findings evidenced the anti-inflammatory effects of DOP on the LL-37-induced rosacea mouse model. DOP could inhibit NF-κB activation, suppress neutrophil infiltration, and reduce pro-inflammatory cytokines production, which may be the reason for DOP protecting against rosacea. CONCLUSION: This study may propose an active candidate with great potential for rosacea drug development and lay a solid experimental foundation for promoting DOP application in rosacea therapy.

Genome-Wide Identification of R2R3-MYB Family Genes and Their Response to Stress in Dendrobium nobile.

BACKGROUND: R2R3-MYB genes comprise one of the largest and most important gene families in plants, and are involved in the regulation of plant growth and development as well as responses to abiotic stresses. However, the functions of R2R3-MYB genes in Dendrobium nobile remains largely unknown. METHODS: Here, a comprehensive genome-wide analysis of D. nobile R2R3-MYB genes was performed, in which phylogenic relationships, gene structures, motif composition, chromosomal locations, collinearity analysis, and cis-acting elements were investigated. Moreover, the expression patterns of selected DnMYB genes were analyzed in various tissues and under different abiotic stresses. RESULTS: In total, 125 DnMYB genes were identified in the D. nobile genome, and were subdivided into 26 groups based on phylogenetic analysis. Most genes in the same subgroup showed similar exon/intron structure and motif composition. All the DnMYB genes were mapped to 19 chromosomes with the co-linearity relationship. Reverse transcription-quantitative real-time PCR (RT-qPCR) results showed that 8 DnMYBs exhibited different expression patterns in different plant tissues, and were differentially expressed in response to abscisic acid, methyl jasmonate, low-temperature stress. CONCLUSIONS: This work contributes to a comprehensive understanding of the R2R3-MYB gene family in D. nobile, and provides candidate genes for future research on abiotic stress in this plant.

Transcriptomics combined with physiological analysis provided new insights into the Zn enrichment capacity and tolerance mechanism of Dendrobium denneanum Kerr.

In this study, we investigated the tolerance and accumulation capacity of Dendrobium denneanum Kerr (D.denneanum) by analyzing the growth and physiological changes of D.denneanum under different levels of Zn treatments, and further transcriptome sequencing of D.denneanum leaves to screen and analyze the differentially expressed genes. The results showed that Zn400 treatment (400 mg·kg-1) promoted the growth of D.denneanum while both Zn800 (800 mg·kg-1) and Zn1600 treatment (1600 mg·kg-1) caused stress to D.denneanum. Under Zn800 treatment (800 mg·kg-1), the resistance contribution of physiological indexes was the most obvious: antioxidant system, photosynthetic pigment, osmoregulation, phytochelatins, and ASA-GSH cycle (Ascorbic acid-Glutathione cycle). D.denneanum leaves stored the most Zn, followed by stems and roots. The BCF(Bioconcentration Factor) of the D.denneanum for Zn were all more than 1.0 under different Zn treatments, with the largest BCF (1.73) for Zn400. The transcriptome revealed that there were 1500 differentially expressed genes between Zn800 treatment and group CK, of which 842 genes were up-regulated and 658 genes were down-regulated. The genes such as C4H, PAL, JAZ, MYC2, PP2A, GS, and GST were significantly induced under the Zn treatments. The differentially expressed genes were associated with phenylpropane biosynthesis, phytohormone signaling, and glutathione metabolism. There were three main pathways of response to Zn stress in Dendrobium: antioxidant action, compartmentalization, and cellular chelation. This study provides new insights into the response mechanisms of D.denneanum to Zn stress and helps to evaluate the phytoremediation potential of D.denneanum in Zn-contaminated soils.

Sesquiterpenoids and bibenzyl derivative from Dendrobium hercoglossum.

Three new sesquiterpenoids, dendrohercoglin A - C (1-3), and one new bibenzyl derivative, dendronbiline D (4), together with nine known sesquiterpenoids (5-13) were isolated from Dendrobium hercoglossum. The structures of the new compounds were elucidated by extensive spectroscopic analysis as well as NMR and ECD calculations. All the compounds were evaluated for their neuroprotective and anti-inflammatory activities. Compounds 2 and 3 increased the H2O2-damaged SH-SY5Y cell viabilities from 43.3% to 58.6% and 68.4%, respectively. Compound 4 exhibited pronounced anti-inflammatory activity with IC50 value of 9.5 ± 0.45 µM which was superior to the reference compound quercetin (IC50: 15.7 ± 0.89 µM).

Antioxidant and L-asparaginase activities of culturable endophytic fungi from ornamental Dendrobium orchids.

This study reports the antioxidant potential and L-asparaginase production of culturable fungal endophytes from Dendrobium orchids in Malaysia. Twenty-nine isolates were screened using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay to determine their free radical scavenging activities and antioxidant capacity (IC50 and AEAC). L-asparaginase production of fungal endophytes was detected by the qualitative plate assay, and the enzyme activities estimated via the Nesslerization method. All 29 endophytic isolates exhibited various degrees of radical scavenging activities (35.37%-77.23%), with Fusarium fujikuroi (D1) identified as having the highest antioxidant capacity (IC50 6.097 mg/mL) and the highest AEAC value (11.55  mg/g). For L-asparaginase production, the majority of the isolates (89.66%) showed positive results, especially among the culturable species of Fusarium, Trichoderma, and Daldinia. Most Fusarium spp. were able to produce L-asparaginase (80.77%), but the highest L-asparaginase activity was detected in Daldinia eschscholtzii (D14) with 2.128 units/mL. Results from this study highlighted the potential of endophytic fungi from medicinal orchids (Dendrobium sp.) as natural sources of bioactive compounds to be developed into novel antioxidants and anticancer drugs.

Phytochemical Profile of Alkaloid Extract from Dendrobium huoshanense and Inhibitory Effects against Oxidative Stress in H2 O2 -Induced PC12 Cells.

This study aimed to explore the alkaloid profile of Dendrobium huoshanense and determine the potential protective effect against oxidative damage. The crude D. huoshanense alkaloid extract (DHAE) was obtained by 70 % ethanol extraction and liquid-liquid partition. DHAE contained specific alkaloid components with abundant 6-hydroxynobiline (58.15 %) and trace dendrobine (3.23 %) in the preliminary HPLC fingerprint and GC-MS analysis, which was distinguished from D. officinale or D. nobile. Subsequently, six alkaloids including 6-hydroxynobiline, 2-hydroxy dendrobine, nobilonine, dendrobine, Findlayines D and trans-dendrochrysanine were identified in the purified DHAE (namely DHSAE-3, DHSAE-3') via further solid phase extraction coupled with UPLC-MS/MS analysis. Meanwhile, pretreatment with DHAE or DHSAE (0.5, 5 µg/mL) increased cell viability by 14.0-57.4 % compared to that of H2 O2 -induced PC12 Model cells. Among them, 5 µg/mL DHSAE-3-treated cells displayed a pronounced reversion than the positive vitamin E (p<0.01). Furthermore, a clear cellular morphological restoration and 38.4 % reduction in intracellular reactive oxidative species level were achieved. Our findings suggest that D. huoshanense has a characteristic alkaloid profile represented by abundant 6-hydroxynobiline, and DHAEs exhibit obvious protection against oxidative neuronal damage. Overall, this study indicates that DHAEs might be used to inhibit oxidative stress and provide a source to develop novel neuroprotective drugs.

The effect of Dendrobium officinale extract in inhibiting the senescence of H2O2-induced fibroblasts based on the senescence-associated secretory phenotype.

BACKGROUND: Dendrobium officinale is widely used for a long time in China, with effect of antioxidation, antitumor, enhancing immunity and so on. In recent years, Dendrobium officinale has been gradually used in cosmetics due to its powerful beauty effects. AIMS: Based on senescence-associated secretory phenotype (SASP), we studied the antiaging effect of Dendrobium officinale extract (DOE) on skin. METHODS: The senescent model of human skin fibroblasts was established by the induction of H2O2, and the content of SASP factors was tested after the treatment of DOE, such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-1 (MMP-1). RESULTS: It was found that after the treatment with different concentrations of DOE, the contents of IL-6, MCP-1 and MMP-1 all decreased in different degrees. CONCLUSIONS: It indicated that DOE could inhibit the secretion of SASP factors and was a promising natural antiaging agent.

Co-expressed network analysis based on 289 transcriptome samples reveals methyl jasmonate-mediated gene regulatory mechanism of flavonoid compounds in Dendrobium catenatum.

Flavonoids are momentous bioactive ingredients in orchid plant Dendrobium catenatum (D. catenatum), which are bioactive compounds with great medical and commercial potential. However, the accurate dissection of flavonoids profiling and their accumulation mechanism are largely unknown. In this study, methyl jasmonate (MeJA) treatment was used to investigate the change of flavonoids content and transcripts in two D. catenatum clones (A6 and B1). We identified 40 flavonoids using liquid chromatograph mass spectrometer (LC-MS). By weighted gene co-expressed network analysis (WGCNA) of flavonoids content and transcript expression of MeJA-treated samples, 37 hub genes were identified. Among them, DcCHIL, DcFLS, and DcDFR were highly correlation with two key transcription factors DcWRKY3/4 by correlation analysis of large-scale transcriptome data and above hub genes expression. Furthermore, transient overexpression of DcWRKY3/4 in tobacco leaves significantly increased the content of flavonoids. This study identified flavonoid profiling and built a new approach to mine regulatory mechanism of flavonoids in D. catenatum. These valuable flavonoids and gene resources will be key for understanding and harnessing natural flavonoids products in pharmaceuticals and foods industry of D. catenatum.

Dendrobium nobile Lindl ameliorates learning and memory deficits in scopolamine-treated mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium nobile Lindl (DNL), a valued time-honored herb, possesses immune-boosting and age-delaying properties, has been widely used to treat hyperglycemia and neurological diseases, and is probably a potential drug for improving learning and memory. Scopolamine (Scop), an antagonist for muscarinic receptors, potentially impairing intelligence and memory. AIM OF THE STUDY: This investigation aimed to assess the efficacy of DNL in alleviating scopolamine-induced cognitive deficits in mice and its mechanisms. MATERIALS AND METHODS: We utilized the open-field test, novel object recognition test (NOR), and Morris water maze test (MWM) to assess the potential of DNL in ameliorating learning and memory dysfunction caused by scopolamine in mice. Enzyme-linked immunosorbent assay (ELISA) was employed to measure Choline acetyltransferase (ChAT) content and Acetylcholinesterase (AChE) activities in the brain, and oxidative stress-related factors in the serum, including Malondialdehyde (MDA), Superoxide dismutase (SOD), and glutathione (GSH) content. RESULTS: Scopolamine injection significantly reduced the discrimination index of mice in the NOR test and impaired their performance in the MWM test, as demonstrated by longer escape latency, fewer target crossings, and less time spent in the target quadrant in the MWM. After 25 days of administration, DNL increased the discrimination index of the scopolamine-treated mice in the NOR test. DNL reduced the escape latency in the MWM test in the model mice. DNL increased the target crossing number and the percentage of time spent in the target quadrant in the MWM test. ELISA experiments indicated that DNL decreased the AChE activities, increased the ChAT activities, and modulated oxidative stress makers (GSH, SOD, and MDA) in scopolamine-induced mice. CONCLUSIONS: DNL may improve the learning and memory in mice treated with scopolamine, possibly by modulating oxidative stress and impaired cholinergic function.

Dendrobium nobile Lindl. alkaloid decreases Tau hyperphosphorylation via regulating PI3K/Akt/GSK-3ß pathway in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANT: Dendrobium is a traditional and precious Chinese medicinal herb. The Compendium of Materia Medica describes its effects as "benefiting intelligence and dispelling shock, lightning the body and extending life". Dendrobium nobile Lindl. is a precious variety of Dendrobium. Our previous data showed Dendrobium nobile Lindl. alkaloid (DNLA) has significant neuroprotective effects and can improve cognitive dysfunction. However, the specific effects and mechanisms of action of its main active component, DNLA, on cognitive dysfunction caused by Tau hyperphosphorylation, are still unclear. AIM OF THE RESEARCH: This study aimed to determine the effects of DNLA on phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase 3ß (GSK-3ß) pathway, thus to explore the mechanisms of DNLA to inhibit Tau hyperphosphorylation. MATERIALS AND METHODS: We used wortmannin (WM) and GF-109203X (GFX)-induced hyperphosphorylation of Tau in N2a cells and rats to detect the protective mechanism of DNLA in vivo and in vitro. In vitro, the effect of modeling method on Tau hyperphosphorylation was screened and verified by Western Blotting (WB), and the regulation of Tau hyperphosphorylation and PI3K/Akt/GSK-3ß pathway by different concentrations of DNLA was detected by WB. In vivo, MWM was used to detect the effect of DNLA on model rats, and then Nissl staining was used to detect the loss of neurons. Finally, WB was used to detect the regulation of Tau hyperphosphorylation and PI3K/Akt/GSK-3ß pathway by different concentrations of DNLA. RESULTS: DNLA could rescue the abnormal PI3K/Akt/GSK-3ß pathway and reverse the hyperphosphorylation of Tau induced by WM and GFX in N2a cells. Furthermore, DNLA improved the learning and memory of WM and GFX-induced model rats. Moreover, DNLA regulated PI3K/Akt/GSK-3ß pathway and reduced the p-Tau and neuronal damage in the hippocampus of model rats. CONCLUSION: DNLA may be a promising candidate for reducing hyperphosphorylation of Tau.

Structure, Health Benefits, Mechanisms, and Gut Microbiota of Dendrobium officinale Polysaccharides: A Review.

Dendrobium officinale polysaccharides (DOPs) are important active polysaccharides found in Dendrobium officinale, which is commonly used as a conventional food or herbal medicine and is well known in China. DOPs can influence the composition of the gut microbiota and the degradation capacity of these symbiotic bacteria, which in turn may determine the efficacy of dietary interventions. However, the necessary analysis of the relationship between DOPs and the gut microbiota is lacking. In this review, we summarize the extraction, structure, health benefits, and related mechanisms of DOPs, construct the DOPs-host axis, and propose that DOPs are potential prebiotics, mainly composed of 1,4-ß-D-mannose, 1,4-ß-D-glucose, and O-acetate groups, which induce an increase in the abundance of gut microbiota such as Lactobacillus, Bifidobacterium, Akkermansia, Bacteroides, and Prevotella. In addition, we found that when exposed to DOPs with different structural properties, the gut microbiota may exhibit different diversity and composition and provide health benefits, such as metabolism regulations, inflammation modulation, immunity moderation, and cancer intervention. This may contribute to facilitating the development of functional foods and health products to improve human health.

The Integration of the Metabolome and Transcriptome for Dendrobium nobile Lindl. in Response to Methyl Jasmonate.

Dendrobium nobile Lindl., as an endangered medicinal plant within the genus Dendrobium, is widely distributed in southwestern China and has important ecological and economic value. There are a variety of metabolites with pharmacological activity in D. nobile. The alkaloids and polysaccharides contained within D. nobile are very important active components, which mainly have antiviral, anti-tumor, and immunity improvement effects. However, the changes in the compounds and functional genes of D. nobile induced by methyl jasmonate (MeJA) are not clearly understood. In this study, the metabolome and transcriptome of D. nobile were analyzed after exposure to MeJA. A total of 377 differential metabolites were obtained through data analysis, of which 15 were related to polysaccharide pathways and 35 were related to terpenoids and alkaloids pathways. Additionally, the transcriptome sequencing results identified 3256 differentially expressed genes that were discovered in 11 groups. Compared with the control group, 1346 unigenes were differentially expressed in the samples treated with MeJA for 14 days (TF14). Moreover, the expression levels of differentially expressed genes were also significant at different growth and development stages. According to GO and KEGG annotations, 189 and 99 candidate genes were identified as being involved in terpenoid biosynthesis and polysaccharide biosynthesis, respectively. In addition, the co-expression analysis indicated that 238 and 313 transcription factors (TFs) may contribute to the regulation of terpenoid and polysaccharide biosynthesis, respectively. Through a heat map analysis, fourteen terpenoid synthetase genes, twenty-three cytochrome P450 oxidase genes, eight methyltransferase genes, and six aminotransferase genes were identified that may be related to dendrobine biosynthesis. Among them, one sesquiterpene synthase gene was found to be highly expressed after the treatment with MeJA and was positively correlated with the content of dendrobine. This study provides important and valuable metabolomics and transcriptomic information for the further understanding of D. nobile at the metabolic and molecular levels and provides candidate genes and possible intermediate compounds for the dendrobine biosynthesis pathway, which lays a certain foundation for further research on and application of Dendrobium.