Asiaticoside exerts neuroprotection through targeting NLRP3 inflammasome activation.

BACKGROUND: Parkinson's disease (PD), a neurodegenerative disorder, is characterized by motor symptoms due to the progressive loss of dopaminergic neurons in the substantia nigra (SN) and striatum (STR), alongside neuroinflammation. Asiaticoside (AS), a primary active component with anti-inflammatory and neuroprotective properties, is derived from Centella asiatica. However, the precise mechanisms through which AS influences PD associated with inflammation are not yet fully understood. PURPOSE: This study aimed to explore the protective mechanism of AS in PD. METHODS: Targets associated with AS and PD were identified from the Swiss Target Prediction, Similarity Ensemble Approach, PharmMapper, and GeneCards database. A protein-protein interaction (PPI) network was constructed to identify potential therapeutic targets. Concurrently, GO and KEGG analyses were performed to predict potential signaling pathways. To validate these mechanisms, the effects of AS on 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in mice were investigated. Furthermore, neuroinflammation and the activation of the NLRP3 inflammasome were assessed to confirm the anti-inflammatory properties of AS. In vitro experiments in BV2 cells were then performed to investigate the mechanisms of AS in PD. Moreover, CETSA, molecular docking, and molecular dynamics simulations (MDs) were performed for further validation. RESULTS: Network pharmacology analysis identified 17 potential targets affected by AS in PD. GO and KEGG analyses suggested the biological roles of these targets, demonstrating that AS interacts with 149 pathways in PD. Notably, the NOD-like receptor signaling pathway was identified as a key pathway mediating AS's effect on PD. In vivo studies demonstrated that AS alleviated motor dysfunction and reduced the loss of dopaminergic neurons in MPTP-induced PD mice. In vitro experiments demonstrated that AS substantially decreased IL-1ß release in BV2 cells, attributing this to the modulation of the NLRP3 signaling pathway. CETSA and molecular docking studies indicated that AS forms a stable complex with NLRP3. MDs suggested that ARG578 played an important role in the formation of the complex. CONCLUSION: In this study, we first predicted that the potential target and pathway of AS's effect on PD could be NLRP3 protein and NOD-like receptor signaling pathway by network pharmacology analysis. Further, we demonstrated that AS could alleviate symptoms of PD induced by MPTP through its interaction with the NLRP3 protein for the first time by in vivo and in vitro experiments. By binding to NLRP3, AS effectively inhibits the assembly and activation of the inflammasome. These findings suggest that AS is a promising inhibitor for PD driven by NLRP3 overactivation.

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.

Effect of Piper nigrum essential oil in dextran sulfate sodium (DSS)-induced colitis and its potential mechanisms.

BACKGROUND: Piper nigrum essential oil (PnEO) possesses pleasant aroma, unique flavor, and various bioactivities; however, its role against colitis remains unclear. PURPOSE: In this study, we investigated the role of PnEO in relieving colitis and explored its potential mechanisms in a mouse model of dextran sulfate sodium (DSS)-induced colitis. METHODS: Initially, we identified and quantified the components of PnEO by gas chromatography-mass spectrometry (GC-MS). Subsequently, we investigated the protective role of PnEO (50 and 200 mg/kg) in DSS-induced colitis in mice by evaluating disease activity index (DAI) scores and colon length, and performing histological analyses. Eyeball blood was collected and cytokines were determined using ELISA kits. The anti-inflammatory mechanisms of PnEO were analyzed by western blot (WB) and immunohistochemistry (IHC). The intestinal barrier function was evaluated according to tight junction (TJ) protein mRNA levels. We used 16S rRNA gene sequencing to analyze the intestinal microflora of mouse cecal contents. RESULTS: Supplementation with PnEO (50 and 200 mg/kg) increased colon length and improved colon histopathology. PnEO regulated inflammatory responses by downregulating TLR4/MAPKs activation, thereby reducing the release of cytokines and mediators. Moreover, it also protected the intestinal barrier through enhancing the expression of claudin-1, claudin-3, occludin, ZO-1, and mucin 2. 16S rRNA gene sequencing revealed that PnEO (200 mg/kg) decreased the abundance of Akkermansia in the gut microbiome. CONCLUSION: PnEO treatment (50 and 200 mg/kg) relieved DSS-induced colitis by inhibiting TLR4/MAPK pathway and protecting intestinal barrier, and high-dose PnEO exhibited better effects. Moreover, PnEO (200 mg/kg) regulated key compositions of the gut microbiome, which indicated that it had therapeutic potential for sustaining gut health to lower the risk of colitis.

The potential of Panax notoginseng against COVID-19 infection.

The COVID-19 pandemic has changed the world and has presented the scientific community with unprecedented challenges. Infection is associated with overproduction of proinflammatory cytokines secondary to hyperactivation of the innate immune response, inducing a cytokine storm and triggering multiorgan failure and significant morbidity/mortality. No specific treatment is yet available. For thousands of years, Panax notoginseng has been used to treat various infectious diseases. Experimental evidence of P. notoginseng utility in terms of alleviating the cytokine storm, especially the cascade, and improving post-COVID-19 symptoms, suggests that P. notoginseng may serve as a valuable adjunct treatment for COVID-19 infection.

Ginsenoside F2 enhances glucose metabolism by modulating insulin signal transduction in human hepatocarcinoma cells.

Background: Ginsenoside F2 (GF2), a minor component of Panax ginseng, has been reported to possess a wide variety of pharmacological activities. However, its effects on glucose metabolism have not yet been reported. Here, we investigated the underlying signaling pathways involved in its effects on hepatic glucose. Methods: HepG2 cells were used to establish insulin-resistant (IR) model and treated with GF2. Cell viability and glucose uptake-related genes were also examined by real-time PCR and immunoblots. Results: Cell viability assays showed that GF2 up to 50 µM did not affect normal and IR-HepG2 cell viability. GF2 reduced oxidative stress by inhibiting phosphorylation of the mitogen-activated protein kinases (MAPK) signaling components such as c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 MAPK, and reducing the nuclear translocation of NF-κB. Furthermore, GF2 activated PI3K/AKT signaling, upregulated the levels of glucose transporter 2 (GLUT-2) and GLUT-4 in IR-HepG2 cells, and promoted glucose absorption. At the same time, GF2 reduced phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression as well as inhibiting gluconeogenesis. Conclusion: Overall, GF2 improved glucose metabolism disorders by reducing cellular oxidative stress in IR-HepG2 cells via MAPK signaling, participating in the PI3K/AKT/GSK-3ß signaling pathway, promoting glycogen synthesis, and inhibiting gluconeogenesis.

Penazaphilones J-L, Three New Hydrophilic Azaphilone Pigments from Penicillium sclerotiorum cib-411 and Their Anti-Inflammatory Activity.

Penazaphilones J-L (1-3), three new hydrophilic azaphilone pigments, as well as six known compounds, were discovered from the filamentous fungus Penicillium sclerotiorum cib-411. Compounds 1-3 were structurally elucidated by the detailed interpretation of their 1D and 2D NMR spectroscopic data. Compound 1 is an unprecedented hybrid of an azaphilone and a glycerophosphate choline. Compounds 2 and 3 each contain an intact amino acid moiety. The bioassay showed that compound 3 exhibited significant anti-inflammatory activity. Concretely, compound 3 significantly suppressed the NO production, the expression levels of COX-2, IL-6, IL-1ß, and iNOS mRNA in LPS-stimulated RAW264.7 cells. Moreover, treatment of compound 3 prevented the translocation of NF-κB through inhibiting the phosphorylation of PI3K, PDK1, Akt, and GSK-3ß. Thus, the inhibition of compound 3 against LPS-induced inflammation should rely on its inactivation on NF-κB.

Dendritic cell-targeting polymer nanoparticle-based immunotherapy for cancer: A review.

Cancer immunity is dependent on dynamic interactions between T cells and dendritic cells (DCs). Polymer-based nanoparticles target DC receptors to improve anticancer immune responses. In this paper, DC surface receptors and their specific coupling natural ligands and antibodies are reviewed and compared. Moreover, reaction mechanisms are described, and the synergistic effects of immune adjuvants are demonstrated. Also, extracellular-targeting antigen-delivery strategies and intracellular stimulus responses are reviewed to promote the rational design of polymer delivery systems.

Phenolic compounds from the flowers of Rosa hugonis Hemsl. and their neuroprotective effects.

The fragrant flowers of Rosa hugonis Hemsl. Contain abundant valuable rose oil and carotenoids. However, phytochemical investigation of this resource rich in phenolics with neuroprotective activity in vitro has been rarely reported. Purification of the 70% ethanol extracts from the flowers of R. hugonis by various chromatographic methods resulted in the isolation and characterization of five undescribed acylated flavonoid glycosides (Hugonisflavonoid A-E) together with forty known phenolics. The chemical structures of the undescribed compounds were elucidated by extensive analysis of their spectroscopic data and chemical methods. All the isolates were found from R. hugonis for the first time and evaluated for their neuroprotective effects on 6-OHDA induced injury in PC12 cells. Seventeen compounds displayed remarkable protective effects at concentrations of 10 µM. Hugonisflavonoid E can reduce excessive reactive oxygen species and up-regulate mRNA expression levels of superoxide dismutase 1 and catalase. Additionally, hugonisflavonoid E activated the phosphorylated proteins such as PDK1, Akt and GSk-3ß. These findings suggested that R. hugonis could be a potential source for neuroprotective agents.

A review of pharmacokinetic and pharmacological properties of asiaticoside, a major active constituent of Centella asiatica (L.) Urb.

ETHNOPHARMACOLOGICAL RELEVANCE: Centella asiatica (L.) Urb., a potential medicinal plant, is widely used in orient traditional medicine. Its major active constituents include asiaticoside (AS), madecassoside (MS), asiatic acid and madecassic acid. Thereinto, AS is a pentacyclic triterpenoid saponin with a variety of pharmacological effects including antitumor, neuroprotective and wound healing effects. AIM OF THE STUDY: In this review, we summarize the pharmacokinetics, safety and pharmacological properties of AS. MATERIALS AND METHODS: We gathered information about AS from articles published up to 2022 and listed in Google scholar, PubMed, Web of Science, Elsevier, and similar databases. The keywords used in our search included "asiaticoside", "Centella asiatica", "pharmacokinetics", "nerve", "cancer", "skin", etc. RESULTS: AS appeared to degrade through a first-order reaction and had low biotoxicity. However, the pharmacokinetic properties of AS differed according to species. AS is highly blood-brain-barrier permeable without any harmful side effect. It has a variety of pharmacological effects including anti-neural inflammation and anti-cancer properties, as well as protective properties for the skin, cardiovascular system, and pulmonary system. CONCLUSION: This review comprehensively summarized current information regarding the pharmacokinetic and pharmacological properties of AS, and supported the pharmaceutical value of this compound. Future research should focus on improving bioavailability of AS and conducting clinical assessment.

Network Pharmacology-Based Prediction and Verification of Ginsenoside Rh2-Induced Apoptosis of A549 Cells via the PI3K/Akt Pathway.

Ginsenoside Rh2 (G-Rh2), a rare protopanaxadiol (PPD)-type triterpene saponin, from Panax ginseng has anti-proliferation, anti-invasion, and anti-metastatic activity. However, the mechanisms by which G-Rh2 induces apoptosis of lung cancer cells are unclear. In the present work, a G-Rh2 target-lung cancer network was constructed and analyzed by the network pharmacology approach. A total of 91 compound-targets of G-Rh2 was obtained based on the compound-target network analysis, and 217 targets were identified for G-Rh2 against lung cancer by PPI network analysis. The 217 targets were significantly enriched in 103 GO terms with FDR <0.05 as threshold in the GO enrichment analysis. In KEGG pathway enrichment analysis, all the candidate targets were significantly enriched in 143 pathways, among of which PI3K-Akt signaling pathway was identified as one of the top enriched pathway. Besides, G-Rh2 induced apoptosis in human lung epithelial (A549) cells was verified in this work. G-Rh2 significantly inhibited the proliferation of A549 cells in a dose-dependent manner, and the apoptosis rate significantly increased from 4.4% to 78.7% using flow cytometry. Western blot analysis revealed that the phosphorylation levels of p85, PDK1, Akt and IκBα were significantly suppressed by G-Rh2. All the experimental findings were consistent with the network pharmacology results. Research findings in this work will provide potential therapeutic value for further mechanism investigations.

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.

A review of the immunomodulatory activities of polysaccharides isolated from Panax species.

Panax polysaccharides are biopolymers that are isolated and purified from the roots, stems, leaves, flowers, and fruits of Panax L. plants, which have attracted considerable attention because of their immunomodulatory activities. In this paper, the composition and structural characteristics of purified polysaccharides are reviewed. Moreover, the immunomodulatory activities of polysaccharides are described both in vivo and in vitro. In vitro, Panax polysaccharides exert immunomodulatory functions mainly by activating macrophages, dendritic cells, and the complement system. In vivo, Panax polysaccharides can increase the immune organ indices and stimulate lymphocytes. In addition, this paper also discusses the membrane receptors and various signalling pathways of immune cells. Panax polysaccharides have many beneficial therapeutic effects, including enhancing or activating the immune response, and may be helpful in treating cancer, sepsis, osteoporosis, and other conditions. Panax polysaccharides have the potential for use in the development of novel therapeutic agents or adjuvants with beneficial immunomodulatory properties.