Ginsenosides from Panax ginseng as potential therapeutic candidates for the treatment of inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by a chronic inflammation of the intestine, which significantly affects patients' quality of life. As a perennial plant with the homology of medicine and food, Panax ginseng is known for its substantial anti-inflammatory effects in various inflammatory disorders. Ginsenosides, the main bioactive compounds of P. ginseng, are recognized for their efficacy in ameliorating inflammation. PURPOSE: Over the past decade, approximately 150 studies have investigated the effects of P. ginseng and ginsenosides on IBD treatment and new issues have arisen. However, there has yet to be a comprehensive review assessing the potential roles of ginsenosides in IBD therapy. METHOD: This manuscript strictly adheres to the PRISMA guidelines, thereby guaranteeing systematic synthesis of data. The research articles referenced were sourced from major scientific databases, including Google Scholar, PubMed, and Web of Science. The search strategy employed keywords such as "ginsenoside", "IBD", "colitis", "UC", "inflammation", "gut microbiota", and "intestinal barrier". For image creation, Figdraw 2.0 was methodically employed. RESULTS: Treatment with various ginsenosides markedly alleviated clinical IBD symptoms. These compounds have been observed to restore intestinal epithelia, modulate cellular immunity, regulate gut microbiota, and suppress inflammatory signaling pathways. CONCLUSION: An increasing body of research supports the potential of ginsenosides in treating IBD. Ginsenosides have emerged as promising therapeutic agents for IBD, attributed to their remarkable efficacy, safety, and absence of side effects. Nevertheless, their limited bioavailability presents a substantial challenge. Thus, efforts to enhance the bioavailability of ginsenosides represent a crucial and promising direction for future IBD research.

Panax notoginseng saponins stimulates the differentiation and neurite development of C17.2 neural stem cells against OGD/R injuries via mTOR signaling.

Ischemic stroke remains a major disease worldwide, and most stroke patients often suffer from serious sequelae. Endogenous neurogenesis matters in the repair and regeneration of impaired neural cells after stroke. We have previously reported in vivo that PNS could strengthen the proliferation and differentiation of neural stem cells (NSCs), modulate synaptic plasticity and protect against ischemic brain injuries in cerebral ischemia rats, which could be attributed to mTOR signaling activation. Next, to obtain further insights into the function mechanism of PNS, we evaluated the direct influence of PNS on the survival, differentiation and synaptic development of C17.2 NSCs in vitro. The oxygen glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemic brain injuries. We found that after OGD/R injuries, PNS improved the survival of C17.2 cells. Moreover, PNS enhanced the differentiation of C17.2 cells into neurons and astrocytes, and further promoted synaptic plasticity by significantly increasing the expressions of synapse-related proteins BDNF, SYP and PSD95. Meanwhile, PNS markedly activated the Akt/mTOR/p70S6K pathway. Notably, the mTOR inhibitor rapamycin pretreatment could reverse these desirable results. In conclusion, PNS possessed neural differentiation-inducing properties in mouse C17.2 NSCs after OGD/R injuries, and Akt/mTOR/p70S6K signaling pathway was proved to be involved in the differentiation and synaptic development of C17.2 cells induced by PNS treatment under the in vitro ischemic condition. Our findings offer new insights into the mechanisms that PNS regulate neural plasticity and repair triggered by NSCs, and highlight the potential of mTOR signaling as a therapeutic target for neural restoration after ischemic stroke.

Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023 edition).

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Efficacy of traditional Chinese medicine on diabetic cardiomyopathy in animal models: a systematic review and meta-analysis.

Background: Diabetic cardiomyopathy (DCM) is a severe complication of diabetes that can diminish the quality of life in patients and is a leading cause of death. Research has demonstrated the effectiveness of Traditional Chinese Medicine (TCM) in reducing blood sugar levels and protecting cardiovascular function in both animal models and clinical research studies. Nevertheless, the efficacy of TCM in animal models of DCM has not been analyzed systematically. Method: We searched the following electronic bibliographic databases: Web of Science, PubMed, Cochrane Library, and CNKI(China National Knowledge Infrastructure). Studies that reported the efficacy of TCM in animals with DCM were included. The literature search was conducted using the terms. The data will be restricted from the year 2013 to 24 April 2023, 24 studies were included in the meta-analysis. Result: A total of 24 Traditional Chinese Medicine interventions and 2157 animals met the inclusion criteria. The pooled data revealed that TCM interventions resulted in significant improvements in body weight (BW), heart weight (HW) to body weight ratio (HW/BW), triglyceride (TG) and cholesterol (TC) levels, ejection fraction (EF), fractional shortening (FS) and E/A ratio. Subgroup analysis and meta-regression revealed that the type of TCM, duration of intervention, method of modeling, and animal species were potential sources of heterogeneity. Conclusion: TCM interventions were associated with significant improvements in body weight, heart weight to body weight ratio, triglyceride and cholesterol levels, left ventricular internal dimension in systole, ejection fraction, fractional shortening and E/A ratio. The heterogeneity in the results was found to be potentially due to the type of TCM, duration of intervention, method of modeling, and animal species, as shown in subgroup analysis and meta-regression. Systematic Review Registration: identifier CRD42023402908.

Elucidation of the mechanism of Yiqi Tongluo Granule against cerebral ischemia/reperfusion injury based on a combined strategy of network pharmacology, multi-omics and molecular biology.

BACKGROUND: Ischemic stroke is caused by local lesions of the central nervous system and is a severe cerebrovascular disease. A traditional Chinese medicine, Yiqi Tongluo Granule (YQTL), shows valuable therapeutic effects. However, the substances and mechanisms remain unclear. PURPOSE: We combined network pharmacology, multi-omics, and molecular biology to elucidate the mechanisms by which YQTL protects against CIRI. STUDY DESIGN: We innovatively created a combined strategy of network pharmacology, transcriptomics, proteomics and molecular biology to study the active ingredients and mechanisms of YQTL. We performed a network pharmacology study of active ingredients absorbed by the brain to explore the targets, biological processes and pathways of YQTL against CIRI. We also conducted further mechanistic analyses at the gene and protein levels using transcriptomics, proteomics, and molecular biology techniques. RESULTS: YQTL significantly decreased the infarction volume percentage and improved the neurological function of mice with CIRI, inhibited hippocampal neuronal death, and suppressed apoptosis. Fifteen active ingredients of YQTL were detected in the brains of rats. Network pharmacology combined with multi-omics revealed that the 15 ingredients regulated 19 pathways via 82 targets. Further analysis suggested that YQTL protected against CIRI via the PI3K-Akt signaling pathway, MAPK signaling pathway, and cAMP signaling pathway. CONCLUSION: We confirmed that YQTL protected against CIRI by inhibiting nerve cell apoptosis enhanced by the PI3K-Akt signaling pathway.

Combination of panax ginseng and ginkgo biloba extracts attenuate cerebral ischemia injury with modulation of NLRP3 inflammasome and CAMK4/CREB pathway.

Stroke is a major cause of death and disability throughout the world. A combination of Panax Ginseng and Ginkgo biloba extracts (CGGE) is an effective treatment for nervous system diseases, but the neuroprotective mechanism underlying CGGE remains unclear. Both network analysis and experimental research were employed to explore the potential mechanism of CGGE in treating ischemic stroke (IS). Network analysis identified a total number of 133 potential targets for 34 active ingredients and 239 IS-related targets. What's more, several processes that might involve the regulation of CGGE against IS were identified, including long-term potentiation, cAMP signaling pathway, neurotrophin signaling pathway, and Nod-like receptor signaling pathway. Our studies in animal models suggested that CGGE could reduce inflammatory response by inhibiting the activity of Nod-like receptor, pyrin containing 3 (NLRP3) inflammasome, and maintain the balance of glutamate (Glu)/gamma-aminobutyric acid (GABA) via activating calmodulin-dependent protein kinase type Ⅳ (CAMK4)/cyclic AMP-responsive element-binding protein (CREB) pathway. These findings indicated the neuroprotective effects of CGGE, possibly improving neuroinflammation and excitotoxicity by regulating the NLRP3 inflammasome and CAMK4/CREB pathway.

A Candidate Drug Screen Strategy: The Discovery of Oroxylin A in Scutellariae Radix Against Sepsis via the Correlation Analysis Between Plant Metabolomics and Pharmacodynamics.

Sepsis is an acute systemic infectious disease with high mortality, which urgently needs more effective treatment. Scutellariae radix (SR), a commonly used traditional Chinese medicine (TCM) for clearing heat and detoxification, contains rich natural products possessing anti-inflammatory activity. In previous studies, it was found that the anti-inflammatory activities of SR extracts from different ecological conditions varied wildly. Based on this, in the present study, a screening strategy of antisepsis active components from SR based on correlation analysis between plant metabolomics and pharmacodynamics was established, and the mechanism was explored. First of all, a mass spectrum database of SR (above 240 components) was established to lay the foundation for the identification of plant metabolomics by liquid chromatography tandem mass spectrometry (LC-MS/MS). Through the correlation analysis between plant metabolomics and anti-inflammatory activity of SR from different ecology regions, 10 potential components with high correlation coefficients were preliminarily screened out. After the evaluation of anti-inflammatory activity and toxicity at the cellular level, the pharmacodynamic evaluation in vivo found that oroxylin A had the potentiality of antisepsis both in LPS- and CLP-induced endotoxemia mice. Network pharmacology and Western blot (WB) results indicated that oroxylin A significantly inhibited the toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway, which was further confirmed by secreted embryonic alkaline phosphatase (SEAP) assay. Moreover, the molecular docking analysis indicated that oroxylin A might competitively inhibit LPS binding to myeloid differentiation 2 (MD-2) to block the activation of TLR4. The study provided a feasible research strategy for the screening and discovery of antisepsis candidate drugs from TCM.

Simulated digestion and in vitro fermentation of a polysaccharide from lotus (Nelumbo nucifera Gaertn.) root residue by the human gut microbiota.

Lotus root polysaccharide (LRP) is an active water-soluble polysaccharide with average molecular weight of 1.24 × 104. It was composed of (1 â†’ 4)-α-D-glucan backbone with α-D-glycopyranosyl moieties connected to C-6 positions of the glucose residues as side chains approximately every six residues. However, little information is available for its digestion and fermentation characteristics in vitro. The results showed that the levels of reducing sugars were increased slightly, and the molecular weight was also reduced slightly, in simulated gastric and small intestinal juices. During in vitro fermentation, the total sugar, reducing sugar and glucose contents decreased gradually with increasing fermentation time. The molecular of LRP was degraded and to metabolize into a variety the short-chain fatty acids (SCFAs) such as acetic, propionic, and butyric acids. Furthermore, LRP fermentation decreased the pH of the fermentation broth and increased its absorbance. Meanwhile, LRP modulated the gut microbiota by altering the Firmicutes/Bacteroidetes ratio and increasing the relative abundance of Bifidobacterium. The findings from this study showed that LRP could be developed as potential prebiotic to regulate the composition of gut microbiota, thereby promote the production of SCFAs.

Senkyunolide H protects PC12 cells from OGD/R-induced injury via cAMP-PI3K/AKT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Senkyunolide H (SNH) is a bioactive phthalide isolated from Ligusticum chuanxiong Hort rhizome and was reported to have multiple pharmacological effects. AIM OF THE STUDY: The study was performed to verify the potency of SNH protecting PC12 cells from oxygen glucose deprivation/reperfusion (OGD/R)-induced injury and to elucidate the underlying mechanisms. MATERIALS AND METHODS: OGD/R model was established in PC12 cells and the cell viability was measured by MTT assay. The cell morphology was observed using scanning electron microscope (SEM). The potential targets of SNH and related targets of OGD/R were screened, and a merged protein-protein interaction (PPI) network of SNH and OGD/R was constructed based on the network pharmacology analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used for pathway analysis. Intracellular cAMP level and the protein expression levels were measured to elucidate the underlying mechanisms. RESULTS: SNH pretreatment protected PC12 cells against OGD/R-induced cell death. SNH also significantly protected the cell protrusion. A merged PPI network was constructed and the shared candidate targets significantly enriched in cAMP signaling pathway. The level of intracellular cAMP and the protein level of p-CREB, p-AKT, p-PDK1 and PKA protein were up-regulated after the treatment of SNH compared with OGD/R modeling. CONCLUSIONS: The present study indicated that SNH protected PC12 cells from OGD/R-induced injury via cAMP-PI3K/AKT signaling pathway.

Lingonberry Anthocyanins Inhibit Hepatic Stellate Cell Activation and Liver Fibrosis via TGFß/Smad/ERK Signaling Pathway.

Phytochemicals from lingonberry have rich pharmacological value and may play an essential role in treating liver diseases. We investigated the regulatory role of lingonberry anthocyanins (LA) on HSC activation in vitro and liver fibrogenesis in vivo. The viability of HSCs treated with LA was significantly reduced in a dose-dependent manner at the concentration of 25-100 µg/mL, in which the monomers of LA also reduced the proliferation of HSCs via IC50 assay. The inducer transforming growth factor ß1 (TGFß1) and the effector α-smooth muscle actin (α-SMA) of HSC activation were all decreased both in protein and RNA levels treated by LA. Moreover, LA alleviated CCl4-induced liver fibrosis in rats, reducing collagen aggregation and production and decreasing the hydroxyproline (HYP) and malondialdehyde (MDA) levels in the liver tissue. Moreover, LA reduced the indexes of serum liver fibrosis and reversed the index of serum liver function in CCl4-induced rats. Furthermore, the antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), in the liver tissue and serum were significantly increased upon treatment with LA. Importantly, LA promoted hepatic parenchymal cell proliferation and inhibited the expression of TGFß/Smad/extracellular regulated protein kinase (ERK) signaling pathway-related genes. This study demonstrates the anti-liver fibrosis activity of LA and investigates its mechanism, which may provide a novel strategy for treating liver fibrosis using lingonberry.

A network-based method for mechanistic investigation and neuroprotective effect on treatment of tanshinone â against ischemic stroke in mouse.

ETHNOPHARMACOLOGICAL RELEVANCE: Tanshinone-Ⅰ (TSNⅠ), a member of the mainly active components of Salvia miltiorrhiza Bunge (Dan Shen), which is widely used for the treatment for modern clinical diseases including cardiovascular and cerebrovascular diseases, has been reported to show the properties of anti-oxidation, anti-inflammation, neuroprotection and other pharmacological actions. However, whether TSNⅠ can improve neuron survival and neurological function against transient focal cerebral ischemia (tMCAO) in mice is still a blank field. AIM OF THE STUDY: This study aims to investigate the neuroprotective effects of TSNⅠ on ischemic stroke (IS) induced by tMCAO in mice and explore the potential mechanism of TSNⅠ against IS by combining network pharmacology approach and experimental verification. MATERIALS AND METHODS: In this study, the pivotal candidate targets of TSNⅠ against IS were screened by network pharmacology firstly. Enrichment analysis and molecular docking of those targets were performed to identify the possible mechanism of TSNⅠ against IS. Afterwards, experiments were carried out to further verify the mechanism of TSNⅠ against IS. The infarct volume and neurological deficit were evaluated by 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining and Longa respectively. Immunohistochemistry was used to observe neuronal death in the hippocampus and cortical regions by detecting the change of NeuN. The predicting pathways of signaling-related proteins were assessed by Western blot in vitro and in vivo experiments. RESULTS: In vivo, TSNⅠ was found to dose-dependently decrease mice's cerebral infarct volume induced by tMCAO. In vitro, pretreatment with TSNⅠ could increase cell viability of HT-22 cell following oxygen-glucose deprivation (OGD/R). Moreover, the results showed that 125 candidate targets were identified, Protein kinase B (AKT) signaling pathway was significantly enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and mitogen-activated protein kinases 1 (MAPK1) and AKT1 could be bound to TSNⅠ more firmly by molecular docking analysis, which implies that TSNⅠ may play a role in neuroprotection through activating AKT and MAPK signaling pathways. Meanwhile, TSNⅠ was confirmed to significantly protect neurons from injury induced by IS through activating AKT and MAPK signaling pathways. CONCLUSION: In conclusion, our study clarifies that the mechanism of TSNⅠ against IS might be related to AKT and MAPK signaling pathways, which may provide the basic evidence for further development and utilization of TSNⅠ.

Vina-Ginsenoside R4 from Panax ginseng Leaves Alleviates 6-OHDA-Induced Neurotoxicity in PC12 Cells Via the PI3K/Akt/GSK-3ß Signaling Pathway.

Vina-ginsenoside R4 (VGN4) is the first example of protopanaxatriol saponin possessing sugar chains located at C-3 and C-20 of aglycone. However, to the best of our knowledge, no report has been published on the neuroprotective effect of VGN4. In the present work, we investigated the neuroprotective effect of VGN4 against 6-hydroxydopamine (6-OHDA)-induced toxicity and its potential mechanism. Pretreatment of PC12 cells with VGN4 attenuated 6-OHDA-induced cell damage and cell apoptosis, which was correlated with the decrease of reactive oxygen species and the increase of antioxidant enzyme activities including superoxide dismutase and catalase. In addition, VGN4 markedly decreased nuclear translation of the nuclear factor-κB and PI3K/Akt/GSK/3ß signaling pathway including p85, PDK1, Akt, and GSK-3ß. Further studies revealed that PI3K siRNA attenuated the neuroprotective effect of VGN4 on caspase-3 activity. These data indicate that VGN4 might have the potential to be developed as a new neuroprotective functional food.

Effect of Ultrafine Powderization and Solid Dispersion Formation via Hot-Melt Extrusion on Antioxidant, Anti-Inflammatory, and the Human Kv1.3 Channel Inhibitory Activities of Angelica gigas Nakai.

Angelica gigas Nakai (AGN) was first processed by ultrafine grinding technology and hot-melt extrusion (HME). The potential antioxidant and anti-inflammatory activities of AGN with a different process were compared, and the effect on the human Kv1.3 potassium channel was detected. The process of ultrafine powderization on AGN significantly increased the total phenolic and flavonoid contents, antioxidant activity, and DNA damage protective effect. On the contrary, AGN solid dispersion (AGN-SD) based on Soluplus® showed the highest inhibitory effect on NO production and the human Kv1.3 channel. In addition, AGN-SD inhibited the production of prostaglandin E2 and intracellular reactive oxygen species and the mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, interleukin 1ß, and interleukin 6. Taken together, these results suggest that ultrafine powderization and solid dispersion formation via HME can significantly improve the biological activities of AGN. The results also suggested that ultrafine powderization and HME may be developed and applied in the pharmaceutical industry.

Micelles modified with a chitosan-derived homing peptide for targeted intracellular delivery of ginsenoside compound K to liver cancer cells.

Ginsenoside compound K (CK), a major metabolite of protopanaxadiol ginsenosides, exhibits significant anticancer activities against various cancer cells. However, CK has poor water solubility and low bioavailability, which have limited its application. In this study, A54 peptide was utilized to fabricate CK-loaded micelles (APD-CK) for liver targeting, using deoxycholic acid-O-carboxymethyl chitosan as the vehicle. The average particle size of APD-CK micelles was about 171.4 nm by dynamic light scattering in the hydrated state and their morphology were spherical with good dispersion. An in vitro release assay indicated pH-responsive and sustained release behavior through a mechanism of non-Fickian diffusion. Moreover, the in vitro cytotoxicity of the APD-CK micelles against HepG2 and Huh-7 cells was significantly stronger than that of CK up to 20 µg/mL. Enhanced cellular uptake of micelles in both cell types was established using confocal fluorescence scanning microscopy and flow cytometry. In addition, western blot analysis revealed that APD-CK micelles could promote the protein expression levels of caspase-3, caspase-9, and poly (ADP-ribose) polymerase. Therefore, APD-CK micelles are a potential vehicle for delivering hydrophobic drugs in liver cancer therapy, enhancing drug targeting and anticancer activity.

Two new triterpenoid saponins derived from the leaves of Panax ginseng and their antiinflammatory activity.

BACKGROUND: The leaves and roots of Panax ginseng are rich in ginsenosides. However, the chemical compositions of the leaves and roots of P. ginseng differ, resulting in different medicinal functions. In recent years, the aerial parts of members of the Panax genus have received great attention from natural product chemists as producers of bioactive ginsenosides. The aim of this study was the isolation and structural elucidation of novel, minor ginsenosides in the leaves of P. ginseng and evaluation of their antiinflammatory activity in vitro. METHODS: Various chromatographic techniques were applied to obtain pure individual compounds, and their structures were determined by nuclear magnetic resonance and high-resolution mass spectrometry, as well as chemical methods. The antiinflammatory effect of the new compounds was evaluated on lipopolysaccharide-stimulated RAW 264.7 cells. RESULTS AND CONCLUSIONS: Two novel, minor triterpenoid saponins, ginsenoside LS1 (1) and 5,6-didehydroginsenoside Rg3 (2), were isolated from the leaves of P. ginseng. The isolated compounds 1 and 2 were assayed for their inhibitory effect on nitric oxide production in LPS-stimulated RAW 264.7 cells, and Compound 2 showed a significant inhibitory effect with IC50 of 37.38 µM compared with that of NG-monomethyl-L-arginine (IC50 = 90.76 µM). Moreover, Compound 2 significantly decreased secretion of cytokines such as prostaglandin E2 and tumor necrosis factor-α. In addition, Compound 2 significantly suppressed protein expression of inducible nitric oxide synthase and cyclooxygenase-2. These results suggested that Compound 2 could be used as a valuable candidate for medicinal use or functional food, and the mechanism is warranted for further exploration.

Elucidation of the Mechanisms and Molecular Targets of Yiqi Shexue Formula for Treatment of Primary Immune Thrombocytopenia Based on Network Pharmacology.

Yiqi Shexue formula (YQSX) is traditionally used to treat primary immune thrombocytopenia (ITP) in clinical practice of traditional Chinese medicine. However, its mechanisms of action and molecular targets for treatment of ITP are not clear. The active compounds of YQSX were collected and their targets were identified. ITP-related targets were obtained by analyzing the differential expressed genes between ITP patients and healthy individuals. Protein-protein interaction (PPI) data were then obtained and PPI networks of YQSX putative targets and ITP-related targets were visualized and merged to identify the candidate targets for YQSX against ITP. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out. The gene-pathway network was constructed to screen the key target genes. In total, 177 active compounds and 251 targets of YQSX were identified. Two hundred and thirty differential expressed genes with an P value < 0.005 and |log2(fold change)| > 1 were identified between ITP patient and control groups. One hundred and eighty-three target genes associated with ITP were finally identified. The functional annotations of target genes were found to be related to transcription, cytosol, protein binding, and so on. Twenty-four pathways including cell cycle, estrogen signaling pathway, and MAPK signaling pathway were significantly enriched. MDM2 was the core gene and other several genes including TP53, MAPK1, CDKN1A, MYC, and DDX5 were the key gens in the gene-pathway network of YQSX for treatment of ITP. The results indicated that YQSX's effects against ITP may relate to regulation of immunological function through the specific biological processes and the related pathways. This study demonstrates the application of network pharmacology in evaluating mechanisms of action and molecular targets of complex herbal formulations.

Xinjiang herbal tea exerts immunomodulatory activity via TLR2/4-mediated MAPK signaling pathways in RAW264.7 cells and prevents cyclophosphamide-induced immunosuppression in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: A multi-herb Chinese medicinal formula consisting of a variety of medicinal and edible materials has long been consumed as a hot drink and immune enhancer for its efficiency to increase disease resistance in Xinjiang, China. However, no fundamental data has been collected associated with traditional consumption. The present work was designed to evaluate the immunostimulatory role of Xinjiang herbal tea (XMT-WE) in RAW 264.7 macrophages and cyclophosphamide (CTX)-induced immunosuppression mice model. MATERIALS AND METHODS: RAW 264.7 cells were treated with various concentrations of XMT-WE. Nitric oxide (NO) levels were determined using Griess reagents, and pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α were investigated with a cytometric bead array kit. The effects on mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and TNF-α were investigated. Furthermore, activation of nuclear factor (NF)-κB and AP-1 mitogen-activated protein kinase (MAPK) signaling pathways was investigated. RESULTS: Pre-treatment with XMT-WE significantly increased secretion of NO, IL-6, and TNF-α. In addition, XMT-WE markedly increased expression of iNOS, COX-2, and TNF-α as well as AP-1 and NF-κB translocation from the cytoplasm into the nucleus, which was associated with an increase of phosphorylated ERK, JNK, and p38 as well as membrane receptors such as toll-like receptor (TLR) 2 and TLR4. Moreover, XMT-WE promoted the secretion of interleukin-2 (IL-2) and interferon-γ (IFN-γ) in cyclophosphamide (CTX)-induced immunosuppressive mice. CONCLUSION: These results indicated that XMT-WE at 50 µg/ml exerts immunomodulatory activity via TLR2/4-mediated MAPK signaling pathways in RAW 264.7 cells. Furthermore, in vivo experiments revealed that XMT-WE at the dose of 50 and 100 mg/kg strongly stimulated inflammatory cytokines.

Senkyunolide H protects against MPP+-induced apoptosis via the ROS-mediated mitogen-activated protein kinase pathway in PC12 cells.

Senkyunolide H (SNH) is a phthalide isolated from the rhizome of Ligusticum chuanxiong Hort. that has been reported to have several pharmacological activities, including anti-atherosclerotic, antiproliferative, and cytoprotective effects. In this study, we investigated the neuroprotective effects and potential mechanisms of SNH against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress. We demonstrated that SNH pretreatment significantly attenuated MPP+-induced neurotoxicity and apoptosis in PC12 cells. In addition, SNH attenuated the effect of MPP+ on the expression of the pro-apoptotic factors Bax and caspase-3. Meanwhile, SNH prevented oxidative stress by reducing reactive oxygen species generation, mitochondrial membrane potential loss, cytochrome C release, and malondialdehyde levels while increasing antioxidant enzyme activity (e.g., superoxide dismutase, catalase, and glutathione peroxidase). In addition, SNH inhibited nuclear accumulation of nuclear factor-κB and c-Jun N-terminal kinase and phosphorylation p38 mitogen-activated protein kinases (MAPKs). Overall, this investigation provides novel evidence that SNH exerts neuroprotective effects via the ROS-mediated MAPK pathway and represents a potential preventive or therapeutic agent for neuronal disorders.

A Network-Based Method for Mechanistic Investigation and Neuroprotective Effect on Post-treatment of Senkyunolid-H Against Cerebral Ischemic Stroke in Mouse.

Senkyunolide-H (SEH), a major bioactive compound extracted from Ligusticum chuanxiong, has been reported to be effective in preventing cerebral ischemic stroke (CIS). In this study, we employed network pharmacology to reveal potential mechanism of SEH against CIS on a system level and confirmed the therapeutic effects of SEH on CIS by models of cerebral ischemia-reperfusion in vivo and in vitro. Through protein-protein interaction networks construction of SEH- and CIS-related targets, a total of 62 key targets were obtained by screening topological indices and analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Gene Ontology analysis indicated that SEH might have a role in treating CIS via regulating some biological processes including regulation of transcription from RNA polymerase II promoter, epidermal growth factor receptor signaling pathway, phosphatidylinositol-mediated signaling, and some molecular function, such as transcription factor and protein phosphatase binding and nitric oxide synthase regulator activity. Meanwhile, the Kyoto Encyclopedia of Genes and Genomes analysis showed that phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was significantly enriched. In addition, our result showed that SEH posttreatment significantly decreased the neurological scores, infarct volume, and neuronal death in the middle cerebral artery occlusion mice. Moreover, the PI3K/Akt/nuclear factor kappa B signaling pathway was activated by intragastric administration of 40 mg/kg SEH, as verified by Western blot. In vitro, treatment of PC12 cells with 100 µM SEH markedly reduced cell death induced by oxygen-glucose deprivation through the activation of PI3K/Akt/nuclear factor kappa B pathway, and the therapeutic effect of SEH was obviously inhibited by 10 µM LY294002. In summary, these results suggested that SEH carries a therapeutic potential in CIS involving multiple targets and pathways, and the most crucial mechanism might be through the activation of PI3K/Akt/nuclear factor kappa B (NF-κB) signaling pathway to inhibit inflammatory factor releases and increase the antiapoptosis capacity. Our study furnishes the future traditional Chinese medicine research with a network pharmacology framework.

Enhanced cytotoxic and apoptotic potential in hepatic carcinoma cells of chitosan nanoparticles loaded with ginsenoside compound K.

Ginsenoside compound K (CK) has been shown to exhibit anticancer properties. In this study, chitosan nanoparticles loaded with ginsenoside compound K (CK-NPs) were prepared as a delivery system using a self-assembly technique with amphipathic deoxycholic acid-O carboxymethyl chitosan as the carrier, which improved the water solubility of CK. By evaluating drug loading, entrapment efficiency, and in vitro release behavior, the feasibility of CK-NPs as a drug carrier nanoparticle for the treatment of human hepatic carcinoma cells (HepG2) was investigated. Result revealed that CK and CK-NPs showed a dose-dependent inhibitory effect on HepG2 cells with IC50 values of 23.33 and 16.58 µg/mL, respectively. Furthermore, fluorescence imaging demonstrated that CK-NPs promoted cellular uptake in vitro. Therefore, all results indicated that CK-NPs might be a novel drug delivery system to improve the solubility and enhance the cytotoxic and apoptotic potentials of CK for effective liver cancer chemotherapy.