Potential Anti-inflammatory Mechanisms Research Articles

RNA Sequencing Analyses Reveal the Potential Anti-Inflammatory Mechanisms of Acacetin Against ODG/R Injuries in Microglia

RNA Sequencing Analyses Reveal the Potential Anti-Inflammatory Mechanisms of Acacetin Against ODG/R Injuries in Microglia

Network pharmacology-based strategy combined with molecular docking to explore the potential mechanism of agarwood against recurrent aphthous stomatitis.

To explore the antiinflammatory mechanism of agarwood on recurrent aphthous stomatitis (RAS). RAS is the most common mucosal disease in the oral cavity. The clinical application of traditional Chinese medicine found that agarwood has significant curative effect on peptic ulcer, but the effect and mechanism of agarwood on RAS remain unclear. This study is intended to predict the potential antiinflammatory mechanisms by which agarwood acts on RAS through network pharmacology and molecular docking. TCMSP database was used to screen the active components of agarwood. RAS targets were screened in Genecards, DisGeNET, and OMIM database. Venny, an online tool, screens for interacting genes between the two. Cytoscape software was used to construct the gene regulation map of active compounds target of agarwood. String Database building protein-protein interaction network. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways were enriched in DAVID database. The key active ingredients and core targets were further verified by molecular docking. There were 9 effective compounds and 186 target genes in agarwood; RAS has 793 target genes. There were 41 interacting genes between agarwood and RAS. Interleukin 6, tumor necrosis factor, interleukin 1 beta, and cellular component motif ligand 2 may be key targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses predicted multiple pathways associated with RAS. Molecular docking results showed that the active compounds of agarwood combined well and stably with the target. The Chinese herbal medicine agarwood can relieve the inflammation of RAS through multiple targets and various ways. Its active compounds may be nominated as candidates for antiinflammatory drugs of RAS.

Bioactive Constituents and the Molecular Mechanism of Melastoma dodecandrum Lour. in the Treatment of Inflammation Based on Network Pharmacology and Molecular Docking

Background: Melastoma dodecandrum Lour. (MD) is a component used in traditional Chinese medicine that is widely distributed in southern China. MD has long been used clinically to treat various diseases, such as inflammation. However, the potential anti-inflammatory mechanism of MD remains to be elucidated. Objective: In this study, network pharmacology and experimental validation have been used to explore the underlying mechanism of MD in inflammation. Methods: The chemical composition of MD was determined using ultra-high performance liquid chromatography-electrospray ionization-high resolution mass spectrometry (UHPLC-ESI-HRMS). The effects of MD on pro-inflammatory cytokines, such as NO, i-NOS, IL-1β, and TNF-α, in RAW264.7 cells stimulated by lipopolysaccharide (LPS) were determined by ELISA and QRT-PCR. Through the analysis of multiple databases, targets for the treatment of inflammation with MD were identified. Other extensive analyses included PPI, GO, and KEGG pathway enrichment, which were completed through the use of the STRING database, Cytoscape software, and the DAVID database. Key targets and key components have been selected for molecular docking. Results: A total of 33 active components were identified in MD, and 134 common targets were obtained and used to construct the networks. Of these, 10 core components and 10 core targets of MD in the treatment of inflammation were identified. The GO and KEGG enrichment analyses revealed that the common targets were involved in multiple signaling pathways, including the PI3K-Akt signaling pathway, NOD-like receptor signaling pathway, chemokine signaling pathway, and IL-17 signaling pathway. The molecular docking methods confirmed the high affinity between bioactive molecules of MD and their targets in inflammation. Two core targets (PIK3CA and AKT) and three core components (asiatic acid, apigenin, and kaempferol) were found to be closely related to MD in the treatment of inflammation. In vitro, MD exerted a significant effect on LPS-stimulated NO, IL- 1β, and TNF-α secretion, and iNOS, IL-1β, and TNF-α expressions in macrophages. Conclusion: This study has demonstrated the bioactive constituents and mechanisms of MD in inhibiting the secretion of inflammatory factors and the multicomponent, multitarget, and multipathway treatment characteristics involved in inflammation, but this still needs further in vivo/in vitro experiments.

Elucidating the active ingredients and potential anti-inflammatory mechanism of Qingwei Huanglian Wan

Qingwei Huanglian Wan (QHW) is a traditional Chinese medicine used for treating inflammation. As the compositions of QHW preparations are complex and varied, it has proven difficult to identify the active ingredients in QHW and control the quality. In this study, high-performance liquid chromatography (HPLC) fingerprints, network pharmacology, molecular docking, and the Griess method were used to screen for and verify the potential active ingredients of QHW. First, sixteen batches of QHW were studied as two groups using multivariate statistical analysis. Thirteen peaks were detected in the HPLC results to establish a fingerprint similarity model, and six chemical constituents (phellodendrine hydrochloride, geniposide, berberine hydrochloride, baicalin, wogonoside, and glycyrrhizic acid) were identified. Among these six constituents, four components (glycyrrhizic acid, berberine hydrochloride, baicalin, and wogonoside) were considered as potential active ingredients. Second, network pharmacology, molecular docking, and the Griess method were used to further elucidate the potential active ingredients. There was no significant difference in the NO content of the active ingredients administration group (dose converted into the medium-dose group) and medium-dose QHW administration group. Then, the contents of berberine hydrochloride, baicalin, wogonoside, and glycyrrhizic acid were determined using the HPLC method. This study provides a comprehensive and reliable strategy for the quality control of QHW preparations and identifies potential active ingredients in QHW. Our methodology may also be useful for studying other traditional Chinese medicines.

Prolonged hyperinsulinemia increases the production of inflammatory cytokines in equine digital lamellae but not in striated muscle

Hyperinsulinemia is the key feature of equine metabolic syndrome (EMS) which leads to debilitating sequelae. Hyperinsulinemia-associated laminitis (HAL) is one of the major sequelae of EMS, although the pathophysiological mechanisms are not well elucidated. Using an equine model, we hypothesized that expression of inflammatory markers would be increased in digital lamellae and striated muscle following prolonged hyperinsulinemia. Healthy Standardbred horses (5.4 ± 1.9 years) were alternately assigned to a prolonged euglycemic-hyperinsulinemic clamp (pEHC) or control group (n = 4 per group). Following a 48 h pEHC or a 48 h infusion of a balanced electrolyte solution (controls), biopsies were collected from digital lamellar tissue, skeletal muscle and cardiac muscle were obtained. All hyperinsulinemic horses developed laminitis regardless of previous health status at enrollment. Protein expression was quantified via Western blotting. A significant (P < 0.05) upregulation of the protein expression of heat shock protein 90 (HSP90), alpha 2 macroglobulin (A2M) and fibrinogen (α, β isoforms), as well as inflammatory cytokines including interleukin-1β were detected in digital lamellae following prolonged hyperinsulinemia. In contrast, protein expression of cytokines and acute phase proteins in heart and skeletal muscle was unchanged following hyperinsulinemia. Upregulation of inflammatory cytokines and acute phase proteins in digital lamellae during prolonged hyperinsulinemia may reveal potential biomarkers and novel therapeutic targets for equine endocrinopathic laminitis. Further, the lack of increase of inflammatory proteins and acute phase proteins in striated muscle following prolonged hyperinsulinemia may highlight potential anti-inflammatory and cardioprotective mechanisms in these insulin-sensitive tissues.

Sclareol exerts an anti-inflammatory effect, possibly through COXs inhibition pathway: In vivo and in silico studies

Chronic and severe inflammation results in many diseases and disorders in humans. Currently, available conventional anti-inflammatory drugs have numerous mild-to-severe side effects. Thus, there is a need for safe, effective, affordable, and alternative anti-inflammatory drugs. This study aimed to evaluate the anti-inflammatory effect of sclareol (SCL), a diterpene alcohol that is the principal ingredient in the refined oil of Salvia sclarea (L.), through in vivo and in silico studies. First, we examined the individual and combined effects of SCL (5, 10, and 20 mg/kg) and standard drugs celecoxib (CXB) or ketoprofen (KPN) at 42 mg/kg (p.o.) on the formalin-induced inflammatory Swiss mice. Additionally, an in silico analysis was conducted to evaluate the potential anti-inflammatory mechanism of this study. For this, we examined the potentiality of SCL and standards to interact with cyclooxygenase (COX) -1 and COX-2 receptors. Our findings suggest that SCL exhibits a dose-dependent anti-inflammatory effect in mice. SCL-20 mg/kg significantly reduced the number of paw licks and paw edema diameters. Moreover, SCL-20 combined with CXB-42 and KPN-42 demonstrated better anti-inflammatory effects. In comparison to the standards, SCL revealed a comparable binding interaction with COX-1 and COX-2 receptors in the molecular docking study. Furthermore, SCL displayed remarkable pharmacokinetic characteristics. In conclusion, SCL significantly and dose-dependently reduced the number of paw licks and edema diameters in animals. Thus, SCL may be responsible for producing an anti-inflammatory effect by interacting with COX-1 and COX-2 receptors.

The Antioxidant and Anti-Inflammatory Properties of Merremia umbellata Extract.

Merremia umbellata Hallier f. (MU) has been used as an anti-inflammatory agent to treat burns and scales. However, the potential anti-inflammatory mechanisms of action of this plant have not been elucidated. This study aimed to assess the antioxidant and anti-inflammatory effects of the leaf and shoot of MU grown in Bangladesh. The MU extract exhibited antioxidant activities as demonstrated by DPPH and ABTS free-radical-scavenging activities and the total polyphenol and total flavonoid contents. MU extract significantly reduced the lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in RAW264.7 macrophage. Accordingly, the gene levels of inducible NO synthase and cyclooxygenase-2 were suppressed. The MU extract alleviated the LPS-induced expression of TLR4, NF-κB, and inflammatory cytokines (TNF-α, IL-6, and IL-1β). The constituents of a MU extract were tentatively identified using UHPLC-PDA-QTOF/MS techniques. The main compounds were identified as 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, quercitrin, and 4,5-dicaffeoylquinic acid. Molecular docking analysis revealed that these compounds interact with TLR4 protein, with quercitrin showing the highest binding affinity among them. Overall, our findings demonstrate the antioxidant and in vitro anti-inflammatory activities of MU and its potential compounds to target the TLR4-NF-κB signaling pathway. These findings are potentially used to further explore promising natural food ingredients that are effective in regulating inflammation.

Deciphering the putative bioactive metabolites and the underlying mechanism of Juniperus horizontalis Moench (Creeping juniper) in the treatment of inflammation using network pharmacology and molecular docking.

To investigate the chemical composition of the alcoholic extract from creeping juniper leaves using HPLC-MS/MS and to elucidate its potential anti-inflammatory mechanism through network-based pharmacology analysis to collectively enable a systematic exploration of the chemical composition, mechanism of action, and therapeutic potential of the alcoholic extract from creeping juniper leaves, providing valuable insights into its suitability as an anti-inflammatory agent. Chemical profiling of the alcoholic extract of creeping juniper leaves using HPLC-MS/MS and revealing its anti-inflammatory mechanism using network-based pharmacology. Further, isolation of some of the identified biomarkers, assessment of their ex-vivo anti-inflammatory activity, and determination of their binding to pro-inflammatory cytokines using molecular docking and dynamics. Thirty-seven compounds were annotated and forwarded to network pharmacology analysis which revealed that the highest interactions were exhibited by quercetin, cosmosiin, myricetin, amentoflavone, hyperoside, isorhamnetin, and quercitrin whereas the most enriched inflammatory targets were IL-2, PGF, VEGFA, and TNFs. PI3K-Akt signaling pathway, arachidonic acid metabolism, and MAPK signaling pathway were found to be the most enriched ones. Six hit compounds were isolated and identified as hyperoside, quercetrin, cupressuflavone, hinokiflavone, amentoflavone, and quercetin. The isolated compounds showed strong anti-inflammatory activity against TNF-α, IL-6, and IL-1β, and molecular docking and dynamics simulation showed that quercetin, quercitrin, and hyperoside had the least binding energy with TNF-α, IL-6, and IL-1B, respectively. Creeping juniper may reduce inflammation based on the suggested multi-compounds and multi-pathways, and that provided the basis for creeping juniper use as a potential anti-inflammatory drug.

Yinhuapinggan granule ameliorates lung injury caused by multidrug-resistant Acinetobacter baumannii via inhibiting NF-κB/NLRP3 pathway

Yinhuapinggan granule (YHPG) is a traditional Chinese medicine prescription with rich clinical experience for the treatment of colds and coughs. The aim of this study is to investigate the protective effect of YHPG on multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infection in vivo and its potential anti-inflammatory mechanism. BALB/c mice were intranasally inoculated with MDR A. baumannii strain to establish the pneumonia infection model, and received intraperitoneally cyclophosphamide to form immunosuppression before attack. YHPG (6, 12 and 18 g/kg) was administered by gavage once a day for 3 consecutive days after infection. The protective effect of YHPG was evaluated by lung index, spleen index, thymus index, pathological changes of lung tissue and inflammatory factors (IL-1β, IL-6 and TNF-α) in serum. The expression of key targets of NF-κB/NLRP3 signaling pathway in vivo was analyzed by immunohistochemistry, immunofluorescence, reverse transcription quantitative PCR (RT-qPCR) and Western blot. The results showed that YHPG improved the lung index and its inhibition rate, immune organ indexes and lung pathological changes in infected mice, and significantly reduced IL-1β, IL-6 and TNF-α levels in serum. In addition, YHPG significantly down-regulated the mRNA and protein expression of NF-κB p65, NLRP3, ASC, Caspase-1, TNF-α, IL-6 and IL-1β in mice lung tissue. The results of the current study demonstrated that YHPG has significant protective effects on mice infected with MDR A.baumannii, which may be related to the regulation of inflammatory factors and NF-κB/NLRP3 signaling pathway, indicating that YHPG has a wide range of clinical application value and provides a theoretical basis for its treatment of MDR A.baumannii infection.

Rutin attenuates inflammation by downregulating AGE-RAGE signaling pathway in psoriasis: Network pharmacology analysis and experimental evidence

BackgroundJueyin granules (JYG) is effective against psoriasis, but its utility components are not clear. Rutin is the main monomer of JYG, its therapeutic effect and mechanism on psoriasis need to be further clarified. PurposeTo explore the potential mechanisms of rutin on psoriasis through network pharmacology and experiments. MethodsIn vitro, cell viability was determined using the CCK8 assay, and inflammatory factors were identified using RT-qPCR. The hub genes and kernel pathways of action were identified by modular pharmacology analysis. In vivo, a BALB/c mice model of psoriasis was induced by Imiquimod (IMQ). The therapeutic effect and action pathway were detected through Western Blotting, RT-qPCR, histopathologic and immunohistochemical analysis. ResultsRutin inhibited cell proliferation and expression of TNF-α and IL-6 in HaCaT cells. The hub genes include APP, INS, and TNF, while the kernel pathways contain the AGE-RAGE signaling pathway. In IMQ-induced psoriasis-like mice, rutin ameliorated skin lesions and inhibited cell proliferation. Rutin could attenuate inflammation by downregulating the AGE-RAGE signaling pathway. ConclusionThis study suggests that rutin can reduce IMQ-induced psoriasis like skin inflammation in mice, and regulation of AGE-RAGE signaling pathway may be one of its potential anti-inflammatory mechanisms. Rutin has a promising therapeutic use for the treatment of psoriasis.

Assessment of the anti-inflammatory mechanism of quercetin 3,7-dirhamnoside using an integrated pharmacology strategy.

Pouzolzia zeylanica (L.) Benn. is a Chinese herbal medicine widely used for its anti-inflammatory and pus-removal properties. To explore its potential anti-inflammatory mechanism, quercetin 3,7-dirhamnoside (QDR), the main flavonoid component of P. zeylanica (L.) Benn., was extracted and purified. The potential anti-inflammatory targets of QDR were predicted using network analysis. These potential targets were verified using molecular docking, molecular dynamics simulations, and invitro experiments. Consequently, 342 potential anti-inflammatory QDR targets were identified. By analyzing the intersection between the protein-protein interaction and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we identified several potential protein targets of QDR, including RAC-alpha serine/threonine-protein kinase (AKT1), Ras-related C3 botulinum toxin substrate 1 (RAC1), nitric oxide synthase 3 (NOS3), serine/threonine-protein kinase mTOR (mTOR), epidermal growth factor receptor (EGFR), growth factor receptor-bound protein 2 (GRB2), and endothelin-1 receptor (EDNRA). QDR has anti-inflammatory activity and regulates immune responses and apoptosis through chemokines, Phosphatidylinositol 3-kinase 3(PI3K)/AKT, cAMP, T-cell receptor, and Ras signaling pathways. Molecular docking analysis showed that QDR has good binding abilities with AKT1, mTOR, and NOS3. In addition, molecular dynamics simulations demonstrated that the protein-ligand complex systems formed between QDR and AKT1, mTOR, and NOS3 have high dynamic stability, and their protein-ligand complex systems possess strong binding ability. In RAW264.7 macrophages, QDR significantly inhibited lipopolysaccharides (LPS)-induced inducible nitric oxide synthase expression, nitric oxide (NO) release and the generation of proinflammatory cytokines IL-6, IL-1β, and TNF-α. QDR downregulated the expression of p-AKT1(Ser473)/AKT1 and p-mTOR (Ser2448)/mTOR, and upregulated the expression of NOS3, Rictor, and Raptor. This indicates that the anti-inflammatory mechanisms of QDR involve regulation of AKT1 and mTOR to prevent apoptosis and of NOS3 which leads to the release of endothelial NO. Thus, our study elucidated the potential anti-inflammatory mechanism of QDR, the main flavonoid found in P. zeylanica (L.) Benn.

Chemical profiling and mechanistic studies of Zhi-Shang-Feng granules against influenza virus by high-performance liquid chromatography coupled with Q exactive focus hybrid quadrupole orbitrap high-resolution mass spectrometry in combination with network pharmacology analysis.

Zhi-Shang-Feng Granules are used in the clinical treatment of influenza to relieve headaches, chills and fever, bronchitis, nasal congestion, neuralgia and other symptoms. To decipher the components responsible for therapeutic effects of Zhi-Shang-Feng g ranules against influenza virus, an analytical method based on high-performance liquid chromatography coupled with Q exactive focus hybrid quadrupole orbitrap high resolution mass spectrometry was developed and the chemical profile of Zhi-Shang-Feng granules was characterized. Then, the identified components were used to conduct network pharmacological analysis and determine the potential mechanism of Zhi-Shang-Feng Granules. As a result, 177 compounds were putatively identified through comprehensive analysis by liquid chromatography coupled with high-resolution mass spectrometry, of which 23 compounds were unambiguously confirmed with reference standards. Components in Zhi-Shang-Feng Granules were found to specifically act on different enzymes, G-protein-coupled receptors, ion channels and transporters in the immune, endocrine, nervous, and circulatory systems. The potential mechanism was related to several biological processes, including cell growth and death, pattern recognition receptor signalling, signalling by interleukins, and lipid metabolism. The combination of chemical profile characterization and network construction provided useful insight into the overall chemical composition of Zhi-Shang-Feng granules and revealed their potential anti-infection, anti-inflammatory and immunoregulatory mechanisms against influenza virus infected disease.

Polar microalgae extracts protect human HaCaT keratinocytes from damaging stimuli and ameliorate psoriatic skin inflammation in mice

BackgroundPolar microalgae contain unique compounds that enable them to adapt to extreme environments. As the skin barrier is our first line of defense against external threats, polar microalgae extracts may possess restorative properties for damaged skin, but the potential of microalgae extracts as skin protective agents remains unknown.PurposeThis study aimed to analyze compound profiles from polar microalgae extracts, evaluate their potential as skin epithelial protective agents, and examine the underlying mechanisms.MethodsSix different polar microalgae, Micractinium sp. (KSF0015 and KSF0041), Chlamydomonas sp. (KNM0029C, KSF0037, and KSF0134), and Chlorococcum sp. (KSF0003), were collected from the Antarctic or Arctic regions. Compound profiles of polar and non-polar microalgae extracts were analyzed using gas chromatography-mass spectrometry (GC-MS). The protective activities of polar microalgae extracts on human keratinocyte cell lines against oxidative stress, radiation, and psoriatic cytokine exposure were assessed. The potential anti-inflammatory mechanisms mediated by KSF0041, a polar microalga with protective properties against oxidative stress, ultraviolet (UV) B, and an inflammatory cytokine cocktail, were investigated using RNA-sequencing analysis. To evaluate the therapeutic activity of KSF0041, an imiquimod-induced murine model of psoriatic dermatitis was used.ResultsPolar microalgae contain components comparable to those of their non-polar counterparts, but also showed distinct differences, particularly in fatty acid composition. Polar microalgae extracts had a greater ability to scavenge free radicals than did non-polar microalgae and enhanced the viability of HaCaT cells, a human keratinocyte cell line, following exposure to UVB radiation or psoriatic cytokines. These extracts also reduced barrier integrity damage and decreased mRNA levels of inflammatory cytokines in psoriatic HaCaT cells. Treatment with KSF0041 extract altered the transcriptome of psoriatic HaCaT cells toward a more normal state. Furthermore, KSF0041 extract had a therapeutic effect in a mouse model of psoriasis.ConclusionsBioactive compounds from polar microalgae extracts could provide novel therapeutics for damaged and/or inflamed skin.

Investigating the potential anti-inflammatory mechanism of benzophenone compounds from the leaves of Aquilaria sinensis (Lour.) Gilg based on network pharmacology and molecular docking strategies

Background Aquilaria sinensis (Lour.) Gilg (ASG) has been used as traditional medicine for centuries. However, the active ingredients from leaves and their anti-inflammatory mechanism are rarely reported. The network pharmacology and molecular docking strategies were applied to explore the potential mechanisms of Benzophenone compounds from the leaves of ASG (BLASG) against inflammation. Methods BLASG-related targets were obtained from the SwissTargetPrediction and PharmMapper databases. Inflammation-associated targets were retrieved from GeneGards, DisGeNET, and CTD databases. Cytoscape software was used to draw a network diagram of BLASG and its corresponding targets. DAVID database was applied for enrichment analyses. A protein-protein interaction (PPI) network was constructed to identify the hub targets of BLASG. Molecular docking analyses were performed by AutoDockTools 1.5.6. Moreover, we used ELISA and qRT-PCR assays to validate the anti-inflammatory effects of BLASG by cell experiments. Results Four BLASG were extracted from ASG, and corresponding 225 potential targets were identified. PPI network analysis indicated that SRC, PIK3R1, AKT1, and other targets were the core therapeutic targets. Enrichment analyses revealed that the effects of BLASG are regulated by targets associated with apoptosis and inflammation-related pathways. In addition, molecular docking revealed that BLASG combined well with PI3K and AKT1. Furthermore, BLASG significantly decreased the inflammatory cytokines levels and down-regulated PIK3R1 and AKT1 gene expression in RAW264.7 cells. Conclusion Our study predicted the potential targets and pathways of BLASG against inflammation, which offered a promising strategy to reveal the therapeutic mechanism of natural active components in the treatment of diseases.

To Explore the Anti-Inflammatory Mechanism of Purslane Based on Network Pharmacology and Molecular Docking

This study was based on network pharmacology and molecular docking combined with experiments in vitro to explore the potential anti-inflammatory mechanism of Portulaca oleracea L. flavone (POL-F). First, the core targets of inflammation in purslane were screened through various databases and software, GO and KEGG analysis and molecular docking were performed. Then, mouse macrophage RAW264.7 was selected as the study object, and the safe experimental concentration of POL-F was confirmed by CCK-8 assay. The cells were divided into a control group, an LPS inflammatory cell model group, and an LPS inflammatory cell model group treated with different concentrations of POL-F. The secretion of NO in each group was detected by the Griess method. The expressions of IL-1β, IL-7, and TNF-α in the supernatant were detected by ELISA. The regulatory effects of POL-F on p-PI3K and PAKT signaling pathway proteins in cells of each group were detected by Western blot. The results showed that Pol-F treated with 100, 200, and 400 μg/ mL had no toxic effect on cells. The three concentrations of POL-F showed inhibitory effect on NO secretion of inflammatory cells, and the inhibitory activity was the best at 400 μg/ml. The expression of p-PI3K and PAKT protein was also inhibited after POL-F treatment. In conclusion, POL-F has a significant inhibitory effect on inflammatory response in vitro.

Iridoids from Patrinia heterophylla and their anti-inflammatory activity

A phytochemical investigation led to the isolation of five undescribed compounds (1–5) from the methanol extract of the rhizomes and roots of Patrinia heterophylla. The structures and configurations of these compounds were characterized by HRESIMS, ECD, and NMR data analyses. These compounds were assayed for their anti-inflammatory potential using LPS-stimulated BV-2 cells, of which compound 4 showed strong nitric oxide (NO) inhibitory effects with an IC50 of 6.48 μM. The potential anti-inflammatory mechanism was examined utilizing Western blotting and molecular docking. Further in vivo anti-inflammatory experiments revealed that compound 4 inhibited the NO production and reactive oxygen species in the zebrafish model.

The correlation between a Th1/Th2 cytokines imbalance and vitamin D level in patients with early chronic obstructive pulmonary disease (COPD), based on screening results.

Objective: This study explored the correlation between a Th1/Th2 cytokines imbalance and 25-hydroxy-vitamin D (vit D) level in early chronic obstructive pulmonary disease (COPD), provided experimental rationales for the role of vit D in the prevention and control of COPD, and elucidated the potential anti-inflammatory mechanism involved. Methods: This study was based on the results of the "Screening and Early Diagnosis of COPD" public health project conducted through Shenzhen Municipal Qianhai Shekou Free Trade Zone Hospital. Patients with early COPD were selected as study participants. A prospective, randomized, and controlled method was employed for assigning eligible participants into three groups, i.e., a COPD lung function (LF) I, COPD LF II, and a healthy group, respectively (n = 40 each). The serum content of tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), interleukin 4 (IL-4), and IL-6 were measured by enzyme-linked immunosorbent assay, and the ratio of IFN-γ/IL-4 treated as a marker for Th1/Th2. The serum concentration of 25-hydroxyl-vit D (25 [OH]D) was quantified by a chemiluminescence assay. Statistical processing was performed, and the correlations between changes in the above parameters with vit D level and LF parameters were examined. Results: There were differences in FEV1pred%, FEV1/FVC, IFN-γ, IL-4, IL-6 and IFN-γ/IL-4 between the healthy group, the COPD LF I group and the COPD LF II group (p < 0.05). In early COPD, Th1/Th2 cytokines was positively correlated with forced expiratory volume/expected value (FEV1pred%) (r = 0.485, p < 0.001) and forced expiratory volume/forced vital capacity (FEV1/FVC) (r = 0.273, p = 0.018); Th1/Th2 cytokines levels positively correlated with vit D level (r = 0.27, p = 0.02), and 25(OH)D level positively correlated with FEV1pred% (r = 0.695, p < 0.001). Conclusion: Vitamin D deficiency was ubiquitous in patients with early COPD. It was positively correlated with the FEV1pred% and FEV1/FVC LF parameters. Accordingly, this study provides experimental rationales for the role of vit D in the prevention and control of COPD and the potential anti-inflammatory mechanisms involved.

Unravelling the anti-inflammatory mechanism of Allium cepa: an integration of network pharmacology and molecular docking approaches.

Allium cepa, commonly known as onion, is a widely consumed spice that possesses numerous pharmacological properties. A. cepa bioactive components are often explored in the treatment of inflammation-related complications. However, the molecular mechanism via which they exert their anti-inflammatory effects remains unknown. Therefore, this study aimed to elucidate the anti-inflammatory mechanism of A. cepa bioactive components. Consequently, the bioactive compounds of A. cepa were obtained from a database, while the potential targets of the sixty-nine compounds with desirable pharmacokinetic properties were predicted. Subsequently, the targets of inflammation were acquired from the GeneCards database. The protein-protein interaction (PPI) between the sixty-six shared targets of the bioactive compounds and inflammation was retrieved from the String database and visualized using Cytoscape v3.9.1 software. Gene Ontology (GO) analysis of the ten core targets from the PPI network revealed that A. cepa bioactive compounds could be involved in regulating biological processes such as response to oxygen-containing compounds and response to inflammation while Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis revealed that A. cepa compounds might modulate pathways including AGE-RAGE signaling pathway, interleukin (IL)-17 signalling pathway, and tumor necrosis factor signaling pathway. Molecular docking analysis showed that 1-O-(4-Coumaroyl)-beta-D-glucose, stigmasterol, campesterol, and diosgenin have high binding affinities for core targets including EGFR, ALB, MMP9, CASP3, and CCL5. This study successfully elucidated the potential anti-inflammatory mechanism of A. cepa bioactive compounds, hence, providing new insights into the development of alternative anti-inflammatory drugs.

Luteolin improves nephropathy in hyperglycemic rats through anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms

Hyperglycemia can also induce the production of free radicals and the progression of inflammatory reactions. The aim of this study is to explore the potential anti-oxidant and anti-inflammatory mechanisms of luteolin in the treatment of diabetic nephropathy.Luteolin significantly reduced blood glucose and BUN levels in streptozotocin-induced diabetic rats and increased serum sodium and chloride levels. Histopathological staining of the kidney showed that luteolin effectively inhibits glycoprotein deposition and production of collagen fibers in the kidney. On Western blotting, luteolin increased anti-oxidant enzymes in the kidney by up-regulating NF-E2-related factor 2 (Nrf2). In DML rats, the expression of inflammatory cytokines decreased significantly with down-regulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). In addition, luteolin inhibited the activation of phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway and the expressions of its downstream apoptosis-related proteins.In conclusion, luteolin slows the progression of nephropathy through anti-hyperglycemic, anti-inflammatory, anti-oxidant, and anti-apoptotic mechanisms.

Phytochemical composition and potential anti-inflammatory and antioxidant mechanisms of leaf extracts of Sida linifolia L. (Malvaceae)

IntroductionThe classes of phytocompounds and in vitro anti-inflammatory and antioxidant potentials of crude aqueous extract (CAE) and ethanol extract (CEE) of Sida linifolia L. leaves were studied. MethodsThe assayed in vitro anti-inflammatory parameters were phospholipase A2 activity, platelet aggregation, albumin denaturation, membrane stabilization, protease inhibition, and heat-induced membrane hemolysis using the human red blood cells (HRBCs) method. Also, antioxidant properties of extracts were determined using reducing power assay, nitric oxide assay, total antioxidant capacity assay, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The anti-inflammatory study used aspirin and prednisolone as reference drugs, while the antioxidant assay deployed butylated hydroxytoluene (BHT), gallic acid, and ascorbic acid as standard drugs. All parameters were determined following conventional procedures. Results and discussionPhytochemical screening of both extracts showed varying amounts of tannins, saponins, flavonoids, steroids, cyanogenic compounds, glycoside, alkaloids, phenolics, and terpenoids. At various concentrations (0.2–1.0 mg/ml), the CAE and CEE exhibited significantly (P < 0.05) high % anti-inflammatory activities similar to the standard drugs (aspirin/prednisolone), and these correlated positively with concentration. However, CAE exhibited better anti-inflammatory activities than CEE across all the parameters assayed. The in vitro antioxidant study revealed that both extracts demonstrated good antioxidant activities, which increased with concentrations. The ranges of IC50 values (in mg/ml) for CAE (0.64–0.92) and CEE (0.51–0.62) showed that CEE possesses more antioxidant potential compared with CAE; however, both extracts were less potent compared with gallic acid (0.47), ascorbic acid (0.32–0.50), and BHT (0.30). ConclusionsThis study suggests that Sida linifolia leaf extracts are rich in some classes of biologically active phytocompounds and exhibit good anti-inflammatory and antioxidant activities.