Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.
Humans ; Ischemic Stroke ; Brain/metabolism* ; Macrophages ; Brain Ischemia/metabolism* ; Microglia/metabolism* ; Gene Expression Profiling ; Anti-Inflammatory Agents ; Neuronal Plasticity/physiology* ; Infarction/metabolism*

Oleanolic acid (OA), a pentacyclic triterpenoid, exhibits a broad spectrum of biological activities, including antitumor, antiviral, antibacterial, anti-inflammatory, hepatoprotective, hypoglycemic, and hypolipidemic effects. Since its initial isolation and identification, numerous studies have reported on the structural modifications and pharmacological activities of OA and its derivatives. Despite this, there has been a dearth of comprehensive reviews in the past two decades, leading to challenges in subsequent research on OA. Based on the main biological activities of OA, this paper comprehensively summarized the modification strategies and structure-activity relationships (SARs) of OA and its derivatives to provide valuable reference for future investigations into OA.
Oleanolic Acid ; Structure-Activity Relationship ; Anti-Inflammatory Agents/pharmacology* ; Triterpenes ; Anti-Bacterial Agents/pharmacology*

BACKGROUND

Post-ERCP pancreatitis (PEP) remains the most common complication following endoscopic retrograde cholangiopancreatography (ERCP). Rectal indomethacin is one of the recommended medications given to prevent pancreatitis in high-risk patients undergoing ERCP.

This study aims to evaluate the effectiveness of diclofenac in preventing PEP, to compare its different routes of administration, and to determine the severity of pancreatitis in patients who develop PEP.

Databases from PubMed, ScienceDirect and COCHRANE Library were searched for randomized controlled trials (RCTs) comparing diclofenac with placebo in the prevention of PEPup to August 2020. Risk ratio at 95% Confidence Intervals (CI) were calculated to evaluate the incidence of the interested outcomes.

Eleven RCTs with a total population of 2,012 were reviewed in this study. Diclofenac was associated with a significant reduction in overall risk of PEP compared with patients with placebo (RR = 0.59; 95%, 0.47 0.74; P < 0.000001), with a mild heterogeneity (P = 0.05; I2 = 41%). Subgroup analyses showed that rectal diclofenac was the superior choice to significantly reduce the overall incidence of PEP(RR = 0.34; 95%, 0.23-0.51; P < 0.000001).

Rectal diclofenac significantly reduces the risk of PEPand therefore, should be recommended as routine for clinical use in adult patients who will undergo ERCP.

OBJECTIVES: This study aimed to investigate how naringenin (Nar) affected the anti-inflammatory, vascula-rization, and osteogenesis differentiation of human periodontal ligament stem cells (hPDLSCs) stimulated by lipopolysaccharide (LPS) and to preliminarily explore the underlying mechanism. METHODS: Cell-counting kit-8 (CCK8), cell scratch test, and Transwell assay were used to investigate the proliferation and migratory capabilities of hPDLSCs. Alkaline phosphatase (ALP) staining, alizarin red staining, lumen-formation assay, enzyme-linked immunosorbent assay, quantitative timed polymerase chain reaction, and Western blot were used to measure the expression of osteopontin (OPN), Runt-related transcription factor 2 (RUNX2), vascular endothlial growth factor (VEGF), basic fibroblast growth factor (bFGF), von Willebrand factor (vWF), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6. RESULTS: We observed that 10 μmol/L Nar could attenuate the inflammatory response of hPDLSCs stimulated by 10 μg/mL LPS and promoted their proliferation, migration, and vascularization differentiation. Furthermore, 0.1 μmol/L Nar could effectively restore the osteogenic differentiation of inflammatory hPDLSCs. The effects of Nar's anti-inflammatory and promotion of osteogenic differentiation significantly decreased and inflammatory vascularization differentiation increased after adding AMD3100 (a specific CXCR4 inhibitor). CONCLUSIONS Nar demonstrated the ability to promote the anti-inflammatory, vascularization, and osteogenic effects of hPDLSCs stimulated by LPS, and the ability was associated with the stromal cell-derived factor/C-X-C motif chemokine receptor 4 signaling axis.
Humans ; Anti-Inflammatory Agents/pharmacology* ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Chemokine CXCL12 ; Lipopolysaccharides/pharmacology* ; Osteogenesis ; Periodontal Ligament/metabolism* ; Receptors, Chemokine/metabolism* ; Stem Cells ; Interleukin-8/metabolism*

This study aims to investigate the therapeutic effect of alcohol extract of root and root bark of Toddalia asiatica(TAAE) on collagen-induced arthritis(CIA) in rats through phosphatidylinoinosidine-3 kinase/protein kinase B(PI3K/Akt) signaling pathway. To be specific, CIA was induced in rats, and then the rats were treated(oral, daily) with TAAE and Tripterygium Glycoside Tablets(TGT), respectively. The swelling degree of the hind leg joints was scored weekly. After 35 days of administration, the histopathological changes were observed based on hematoxylin and eosin(HE) staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the levels of cytokines [tumor necrosis factor-α(TNF-α), interleukin(IL)-6)]. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) staining was performed to detect the apoptosis of synoviocytes in rats. Western blot was used to detect the expression levels of apoptosis-related proteins B-cell lymphoma 2(Bcl-2)-associated X(Bax), Bcl-2, and caspase-3 and pathway-related proteins phosphoinositide 3-kinase(PI3K), phosphorylated(p)-PI3K, protein kinase B(Akt), and p-Akt. RT-qPCR was conducted to examine the mRNA levels of Bax, Bcl-2, caspase-3, TNF-α, IL-6, and IL-1β and pathway-related proteins PI3K, p-PI3K, Akt, and p-Akt. TAAE can alleviate the joint swelling in CIA rats, reduce serum levels of inflammatory cytokines, improve synovial histopathological changes, promote apoptosis of synoviocytes, and inhibit synovial inflammation. In addition, RT-qPCR and Western blot results showed that TAAE up-regulated the level of Bax, down-regulated the level of Bcl-2, and activated caspase-3 to promote apoptosis in synoviocytes. TAAE effectively down-regulated the protein levels of p-PI3K and p-Akt. In this study, TAAE shows therapeutic effect on CIA in rats and reduces the inflammation. The mechanism is that it suppresses PI3K/Akt signaling pathway and promotes synoviocyte apoptosis. Overall, this study provides a new clue for the research on the anti-inflammatory mechanism of TAAE and lays a theoretical basis for the better clinical application of TAAE in the treatment of inflammatory and autoimmune diseases.
Rats ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Caspase 3/genetics* ; Tumor Necrosis Factor-alpha/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Plant Bark ; Anti-Inflammatory Agents/therapeutic use* ; Arthritis, Experimental/chemically induced* ; Inflammation/drug therapy* ; Cytokines/metabolism* ; Proto-Oncogene Proteins c-bcl-2 ; Apoptosis

In this study, the crude polysaccharides was extracted from Shengfupian and purified by Sevag deproteinization. Then, the purified neutral polysaccharide fragment was obtained by the DEAE-52 cellulose chromatography column and Sephadex G-100 co-lumn. The structure of polysaccharides was characterized by ultraviolet spectroscopy, infrared spectroscopy, ion chromatography, and gel permeation chromatography. To investigate the anti-inflammatory activity of Shengfupian polysaccharides, LPS was used to induce inflammation in RAW264.7 cells. The expression of the CD86 antibody on surface of M1 cells, the function of macrophages, and the content of NO and IL-6 in the supernatant were examined. An immunodepression model of H22 tumor-bearing mice was established, and the immunomodulatory activity of Shengfupian polysaccharides was evaluated based on the tumor inhibition rate, immune organ index and function, and serum cytokine levels. Research indicated that Shengfupian polysaccharides(80 251 Da) was composed of arabinose, galactose, glucose, and fructose with molar ratio of 0.004∶0.018∶0.913∶0.065. It was smooth and lumpy under the scanning electron microscope. In the concentration range of 25-200 μg·mL~(-1), Shengfupian polysaccharides exhibited little or no toxicity to RAW264.7 cells and could inhibit the polarization of cells to the M1 type and reduce the content of NO and IL-6 in the cell supernatant. It could suppress the phagocytosis of cells at the concentration of 25 μg·mL~(-1), while enhancing the phagocytosis of RAW264.7 cells within the concentration range of 100-200 μg·mL~(-1). The 200 mg·kg~(-1) Shengfupian polysaccharides could alleviate the spleen injury caused by cyclophosphamide, increase the levels of IL-1β and IL-6, and decrease the level of TNF-α in the serum of mice. In conclusion, Shengfupian polysaccharides has anti-inflammatory effect and weak immunomodulatory effect, which may the material basis of Aconm Lateralis Radix Praeparaia for dispelling cold and relieving pain.
Animals ; Mice ; Interleukin-6/genetics* ; Cytokines/metabolism* ; Polysaccharides/chemistry* ; RAW 264.7 Cells ; Anti-Inflammatory Agents/chemistry* ; Spectrophotometry, Infrared

This study aimed to explore the anti-inflammatory material basis and molecular mechanism of Artemisia stolonifera based on the analysis of the chemical components in different extracted fractions of A. stolonifera and their antioxidant and anti-inflammatory effects in combination with network pharmacology and molecular docking. Thirty-two chemical components were identified from A. stolonifera by ultra-performance liquid chromatography coupled to tandem quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Among them, there were 7, 21 and 22 compounds in water, n-butanol and ethyl acetate fractions, respectively. The antio-xidant capacity of different extracted fractions was evaluated by measuring their scavenging ability against 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl(DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid)(ABTS) free radicals and total antioxidant capacity [ferric reducing antioxidant power(FRAP) assay]. The inflammatory model of RAW264.7 cells was induced by lipopolysaccharide(LPS), and the levels of nitrite oxide(NO), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) in the supernatant and the mRNA expression of related inflammatory factors in cells were used to evaluate the anti-inflammatory effects. The results revealed that ethyl acetate fraction of A. stolonifera was the optimal antioxidant and anti-inflammatory fraction. By network pharmacology, it was found that flavonoids such as rhamnazin, eupatilin, jaceosidin, luteolin and nepetin could act on key targets such as TNF, serine/threonine protein kinase 1(AKT1), tumor protein p53(TP53), caspase-3(CASP3) and epidermal growth factor receptor(EGFR), and regulate the phosphatidylinositol-3-kinase-protein kinase B(PI3K-AKT) and mitogen-activated protein kinase(MAPK) signaling pathways to exert the anti-inflammatory effects. Molecular docking further indicated excellent binding properties between the above core components and core targets. This study preliminarily clarified the anti-inflammatory material basis and mechanism of ethyl acetate fraction of A. stolonifera, providing a basis for the follow-up clinical application of A. stolonifera and drug development.
Antioxidants/chemistry* ; Molecular Docking Simulation ; Artemisia ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Anti-Inflammatory Agents/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Interleukin-6

Flavonoids have been reported to possess significant pharmacological activities,such as antioxidant, anti-inflammatory and anticancer effects. However, the low solubility and low bioavailability limits their clinical application. Nanocrystal technology can solve the delivery problems of flavonoids by reducing particle size, increasing the solubility of insoluble drugs and improving their bioavailability. This article summaries nanosuspension preparation methods and the stabilizers for flavonoid nanocrystals, and reviews the drug delivery routes including oral, Injection and transdermal of flavonoid nanocrystals, to provide information for further research on nanocrystal delivery system of flavonoids.
Flavonoids/pharmacology* ; Pharmaceutical Preparations/chemistry* ; Biological Availability ; Nanoparticles/chemistry* ; Anti-Inflammatory Agents ; Particle Size

Vesicles derived from Chinese medicinal herbs (VCMH) are nano-vesicular entities released by the cells of Chinese medicinal herbs. VCMHs have various biological effects and targeting characteristics, and their component chemicals and functional activities are closely related to the parent plant. VCMH differs from animal-derived vesicles in three ways: stability, specificity, and safety. There are a number of extraction and isolation techniques for VCMH, each with their own benefits and drawbacks, and there is no unified standard. When two or more approaches are used, high quantities of intact vesicles can be obtained more quickly and efficiently. The obtained VCMHs were systematically examined and evaluated. Firstly, they are generally saucer-shaped, cup-shaped or sphere, with particle size of 10-300 nm. Secondly, they contain lipids, proteins, nucleic acids and other active substances, and these components are an important part for intercellular information transfer. Finally, they mostly have good biocompatibility and low toxicity, with anti-inflammatory, antioxidant, anti-tumor and anti-fibrotic effects. As a new drug carrier, VCMHs have outstanding active targeting capabilities, and the capsule form can effectively preserve the drugs, considerably enhancing drug delivery efficiency and stability in vitro and in vivo. The modification of its vesicular structure by suitable physical or chemical means can further create more stable and precise drug carriers. This article reviews the extraction and purification techniques, activity evaluation and application of VCMH to provide information for further research and application of new active substances and targeted drug carriers.
Animals ; Drugs, Chinese Herbal/chemistry* ; Plants, Medicinal ; Antioxidants ; Anti-Inflammatory Agents ; Drug Carriers

Over the past few decades, complementary and alternative treatments have become increasingly popular worldwide. The purported therapeutic characteristics of natural products have come under increased scrutiny both in vitro and in vivo as part of efforts to legitimize their usage. One such product is tea tree oil (TTO), a volatile essential oil primarily obtained from the native Australian plant, Melaleuca alternifolia, which has diverse traditional and industrial applications such as topical preparations for the treatment of skin infections. Its anti-inflammatory-linked immunomodulatory actions have also been reported. This systematic review focuses on the anti-inflammatory effects of TTO and its main components that have shown strong immunomodulatory potential. An extensive literature search was performed electronically for data curation on worldwide accepted scientific databases, such as Web of Science, Google Scholar, PubMed, ScienceDirect, Scopus, and esteemed publishers such as Elsevier, Springer, Frontiers, and Taylor & Francis. Considering that the majority of pharmacological studies were conducted on crude oils only, the extracted data were critically analyzed to gain further insight into the prospects of TTO being used as a neuroprotective agent by drug formulation or dietary supplement. In addition, the active constituents contributing to the activity of TTO have not been well justified, and the core mechanisms need to be unveiled especially for anti-inflammatory and immunomodulatory effects leading to neuroprotection. Therefore, this review attempts to correlate the anti-inflammatory and immunomodulatory activity of TTO with its neuroprotective mechanisms.
Tea Tree Oil/therapeutic use* ; Melaleuca ; Neuroprotection ; Drug Repositioning ; Neuroinflammatory Diseases ; Australia ; Oils, Volatile ; Anti-Inflammatory Agents/pharmacology*