Treatment Of Inflammation-related Diseases Research Articles

Anti-inflammatory activity of the phenol rich fraction of Garcinia pedunculata Roxb (ex. Buch Ham): an in vitro and in vivo study.

Garcinia pedunculata, a tropical plant found abundantly in the north-east region of India, has been used by many traditional healers for various gastrointestinal ailments. Studies are being carried out for the proper pharmacological identification of the compounds as well as the mode of action for the treatment of various diseases. In this study, phytochemistry of the fruit was evaluated, followed by a quantitative analysis of the total phenolic and flavonoid content of the methanolic crude extract as well as different fractions (n-hexane, chloroform, ethyl acetate, and n-butanol). The fraction with the most potent flavonoid and phenolic content was evaluated for its anti-inflammatory activity using both in vitro and in vivo assays. The chloroform fraction of G. pedunculata fruit extract was found to have a substantial amount of phenols and flavonoids. This fraction inhibited the denaturation of BSA and significantly stabilized human RBC membrane compared to the standard drug Diclofenac sodium. The fraction also significantly reduced the formaldehyde-induced paw edema in mice and normalized the blood parameters. This study provides evidence that G. pedunculata fruit extract plays a critical role in anti-inflammatory activity, indicating that it can be a potential candidate for further investigation in the treatment of inflammation-related diseases.

Silkworm pupa protein-derived peptides alleviate LPS-induced inflammatory response in RAW264.7 macrophage cells through the NF-κB/MAPK/PI3K-AKT signaling pathway

A plethora of studies have indicated that protein or peptides derived from food sources possess potential anti-inflammatory activity. In our previous research, we discovered peptides from silkworm pupae (Bombyx mori) exhibited promising anti-inflammatory effects in mice. However, the anti-inflammatory activity of silkworm pupae protein peptides (SPP) has yet to be validated at the cellular level, and its underlying anti-inflammatory mechanisms remain unclear. Therefore, the aim of this study was to explore the anti-inflammatory potential of SPP in lipopolysaccharide (LPS)-induced RAW264.7 inflammation model. Our research findings demonstrated that SPP significantly reduced LPS-induced inflammation in RAW264.7 cells in a dose-dependent manner, including decreased levels of inflammatory mediators (NO, MCP-1, and PEG2) and cytokines (TNF-α, IL-6, and IL-1β). Furthermore, we observed significant downregulation of mRNA and protein expression of iNOS and COX-2 by SPP (p < 0.05). Additionally, SPP exerted its anti-inflammatory effects by inhibiting the NF-κB/MAPK/PI3K signaling pathway. These results suggested that SPP may serve as a novel functional food ingredient for the prevention or treatment of inflammation-related diseases.

Anti-inflammatory activities of some Anthemis species used in the treatment of inflammation-related diseases, GC/MS and LC-MS/MS analysis with bioactivity-guided fractionation

Recent studies have focused on Anthemis sp. because of their rich chemical composition and application in the treatment of diseases associated with inflammation. The purpose of this study was to determine the active chemicals responsible for the anti-inflammatory properties of Anthemis cotula, A. tomentosa, A. austriaca, and A. tinctoria var. tinctoria. Therefore, the 5-Lipoxygenase (5-LOX) was used to assess the anti-inflammatory properties of methanol extracts that were extracted from the aerial parts of the mentioned species, with an IC50 value of 23.88 μg/mL, the methanol extract of A. tinctoria var. tinctoria demonstrated anti-inflammatory effects close to the standard (Indomethacin, IC50: 18.05 μg/mL). Compared to the other extracts, the methanol extract of A. tinctoria var. tinctoria demonstrated significantly greater anti-inflammatory activity. A. tinctoria var. tinctoria and A. tomentosa methanol extracts, which were the most active in comparison to other extracts, were fractionated using the bioactivity-guided fractionation method. Their anti-inflammatory properties were evaluated to determine the compounds responsible for the activity. With an IC50 value of 3.44 μg/mL, the ethyl acetate fraction of A. tinctoria var. tinctoria (ATiEA) was found to be the most active of all the fractions. After ATiEA was further fractionated using column chromatography, it was found that ATiEA-II, one of its sub-fractions, was more effective than other sub-fractions against the 5-LOX, with an IC50 value of 2.93 μg/mL. Furthermore, the sub-fractions' total phenol and flavonoid contents were examined to confirm their anti-inflammatory properties. The sub-fraction ATiEA-II exhibited higher total flavonoid content (743,86 μg QE/g dry weight) and total phenol content (4659.36 μg GA/g dry weight) than other sub-fractions, which was in line with its anti-inflammatory activity. GC/MS and LC-MS/MS were used to clarify the effective compounds of the sub-fraction ATiEA-II. Experiments on the anti-inflammatory properties of different Anthemis sp. have demonstrated the good anti-inflammatory potential of this species. Specifically, ATiEA-II, a sub-fraction of A. tinctoria var. tinctoria, may contain a novel anti-inflammatory drug molecule.

Anti-inflammatory activity of doum palm fruit extract used in the management of benign prostatic hyperplasia

Background: Benign prostatic hyperplasia (BPH) is a frequent health concern in men over the age of 50. It is characterized by an increase in the size of the prostate, which can lead to urinary issues. In the past, the treatment of BPH was limited to surgery. However, the introduction of drugs such as Permixon, based on saw palmetto extract, has revolutionized the management of this disease. This natural plant extract is effective in relieving the symptoms of BPH and can also slow the progression of the disease. The Algerian population consumes several plants for this purpose, such as nettle, galangal, pumpkin seeds, and doum palm. The doum palm (Chamaerops humilis) is a bushy plant with fan leaves that is widely distributed in the Mediterranean region. The terminal bud of this species is edible, however the doum palm has been appreciated by several societies throughout time for its multiple traditional uses and is primarily exploited for its fibers. In addition, this plant has aroused growing interest for its properties, especially in the treatment of benign prostatic hyperplasia. Aims: This study aimed to evaluate the in vitro anti-inflammatory activity of the aqueous extract of the doum palm by the protein denaturation method comparing it to Permixon extracts and corticosteroids in order to valorize this species and confirm its traditional use. Material and Methods: The fruits of Chamaerops humilis L. were dried, powdered, and extracted with aqueous water then screened by various chemical tests. The anti-inflammatory activity was estimated after dilution of each extract using the human serum albumin. Results: When evaluating the anti-inflammatory effect, we observed that the fruit extract exhibited significantly higher activity, with an IC50 of 446,02 mg/mL, too close to that of Permixon (IC50= 423.17 μg/mL) and exceeding that of corticosteroids (IC50= 602,21 mg/mL). All three extracts clearly demonstrated their ability to reduce inflammation. Conclusion: The aqueous extract was found to be an effective anti-inflammatory agent. These results offer promising novel perspectives in the treatment of inflammation-related diseases, especially benign prostatic hyperplasia. Keywords: anti-inflammatory activity, benign prostatic hyperplasia, doum palm, Permixon, secondary active metabolites.

The roles of ubiquitination and deubiquitination of NLRP3 inflammasome in inflammation-related diseases: A review.

The inflammatory response is a natural immune response that prevents microbial invasion and repairs damaged tissues. However, excessive inflammatory responses can lead to various inflammation-related diseases, posing a significant threat to human health. The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is a vital mediator in the activation of the inflammatory cascade. Targeting the hyperactivation of the NLRP3 inflammasome may offer potential strategies for the prevention or treatment of inflammation-related diseases. It has been established that the ubiquitination and deubiquitination modifications of the NLRP3 inflammasome can provide protective effects in inflammation-related diseases. These modifications modulate several pathological processes, including excessive inflammatory responses, pyroptosis, abnormal autophagy, proliferation disorders, and oxidative stress damage. Therefore, this review discusses the regulation of NLRP3 inflammasome activation by ubiquitination and deubiquitination modifications, explores the role of these modifications in inflammation-related diseases, and examines the potential underlying mechanisms.

The Potential Preventive and Therapeutic Roles of NSAIDs in Prostate Cancer.

Prostate cancer (PC) is the second most common type of cancer and the leading cause of death among men worldwide. Preventing the progression of cancer after treatments such as radical prostatectomy, radiation therapy, and hormone therapy is a major concern faced by prostate cancer patients. Inflammation, which can be caused by various factors such as infections, the microbiome, obesity and a high-fat diet, is considered to be the main cause of PC. Inflammatory cells are believed to play a crucial role in tumor progression. Therefore, nonsteroidal anti-inflammatory drugs along with their effects on the treatment of inflammation-related diseases, can prevent cancer and its progression by suppressing various inflammatory pathways. Recent evidence shows that nonsteroidal anti-inflammatory drugs are effective in the prevention and treatment of prostate cancer. In this review, we discuss the different pathways through which these drugs exert their potential preventive and therapeutic effects on prostate cancer.

Discovery and verification of anti-inflammatory-related quality markers in the aerial part of Bupleurum scorzonerifolium by UPLC-Q-TOF-MS/MS and in RAW 264.7 cells and a zebrafish model.

The root of Bupleurum scorzonerifolium Willd. (BS) is officially recognized in the Chinese Pharmacopoeia. In contrast, the aerial part of BS (ABS), accounting for 80% of BS, is typically discarded, causing potential waste of medicinal resources. ABS has shown benefits in the treatment of inflammation-related diseases in China and Spain, and the material basis underlying its anti-inflammatory effects must be systematically elucidated for the rational use of ABS. We aimed to screen and validate the anti-inflammatory quality markers (Q-markers) of ABS and to confirm the ideal time for ABS harvesting. The chemical components and anti-inflammatory effects of ABS from 10 extracted parts were analyzed by UPLC-Q-TOF-MS/MS and in a lipopolysaccharide (LPS)-induced cell model. Anti-inflammatory substances were screened by Pearson bivariate analysis and gray correlation analysis, and the anti-inflammatory effects were verified in a zebrafish tail-cutting inflammation model. HPLC was applied to measure the Q-marker contents of ABS in different harvesting periods. Ten ABS extracts effectively alleviated the increase in LPS-induced proinflammatory cytokines in RAW 264.7 cells. Forty components were identified from them, among which 27 were common components. Eight components were correlated with anti-inflammatory effects, which were confirmed to reverse the expression of proinflammatory and anti-inflammatory factors in a zebrafish model. Chlorogenic acid, hypericin, rutin, quercetin, and isorhamnetin can be detected by HPLC, and the maximum contents of these five Q-markers were obtained in the sample harvested in August. The anti-inflammatory Q-markers of ABS were elucidated by chromatographic-pharmacodynamic-stoichiometric analysis, which served as a crucial basis for ABS quality control.

Evaluation of the anti-inflammatory material basis of Lagotis brachystachya in HepG2 and THP-1 cells

Ethnopharmacological relevance Lagotis brachystachyaMaxim is a traditional ethnic medicine commonly used in Tibet. In Tibetan medicine theory, Lagotis brachystachya is mainly used for the treatment of inflammatory related diseases. However, the active components and mechanism of the anti-inflammatory activity of Lagotis brachystachya are not clear. Aim of the studyThe putative anti-inflammatory active compounds from Lagotis brachystachya Maxim and its anti-inflammation related mechanism involving in the TLR4/MyD88/NF-κB and NLRP3 signaling pathways were investigated. Materials and methodsIn this study, we investigated the anti-inflammatory activity and mechanism of 32 compounds extracted from Lagotis brachystachya in HepG2 and THP-1 cells using the alcohol-induced HepG2 cell injury model and the monosodium urate (MSU) combined with lipopolysaccharide (LPS)-induced THP-1 cell inflammation model. ResultsThe results found that six compounds, including Echinacoside, Quercetin, Homoplantaginin, Tricin-7-O-glucoside, Apigenin and Luteolin-7-O-beta-d-glucopyranoside, were shown to exhibit significant anti-inflammatory effects in both cell models. Furthermore, these compounds were shown to inhibit the TLR4/MyD88/NF-κB and NLRP3 signaling pathways and reduce the release of pro-inflammatory cytokines IL-1β, TNF-α, and IL-6 in both cell models. ConclusionThese findings suggest that Echinacoside, Quercetin, Homoplantaginin, Tricin-7-O-glucoside, Apigenin and Luteolin-7-O-beta-d-glucopyranoside from Lagotis brachystachya have promising potential as natural anti-inflammatory agents for the treatment of inflammatory-related diseases. The discovery of bioactive compounds from this plant opens up possibilities for the development of novel treatments for inflammatory-related diseases, potentially providing alternative or adjunctive options to conventional therapies.

Mineral composition, principal polyphenolic components, and evaluation of the anti-inflammatory, analgesic, and antioxidant properties of Cytisus villosus Pourr leaf extracts

Abstract Cytisus villosus Pourr. (C. villosus) is a medicinal plant belonging to the Fabaceae family, which grows in the Mediterranean area. It is used in traditional medicine against diseases related to inflammation. The objective of the present study was to identify the mineral and polyphenolic composition as well as to evaluate some biological properties including antioxidant, anti-inflammatory, and analgesic activities of C. villosus leaf aqueous extract. The chemical constituents were identified and quantified using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) methods. The antioxidant properties of C. villosus leaves were tested using reducing power (RP), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and 2,2′-diphenyl-1-picrylhydrazyl (DPPH) assays. The anti-inflammatory potency was evaluated in vitro and in vivo using the albumin denaturation test and the carrageenan test, respectively. Furthermore, the analgesic effect was performed in vivo using tail flick, acetic acid-induced contortion, and plantar tests. Mineralogical analysis revealed that potassium and calcium were the most abundant minerals. The analysis and quantification of the phytochemical composition using UPLC-ESI-MS/MS showed that quinic acid (57.478 ± 1.72 mg/kg) was the major compound of the aqueous extract, followed by salicylic acid (17.38 ± 0.2 mg/kg), isoquercetin (16.895 ± 1.01 mg/kg), and gallic acid (15.914 ± 1.51 mg/kg). The extracts showed potent antioxidant activity for all tests used. The highest antioxidant activity was recorded for the DPPH, ABTS and RP methods, with an IC50 of 3.94 ± 0.09, 2.88 ± 0.07, and 1.94 ± 0.10 μg/mL, respectively. Additionally, using the most frequent analgesic assays, the aqueous extract at a dose of 500 mg/kg exhibited a potent analgesic activity. Notably, an interesting inhibition of albumin denaturation was recorded with an IC50 of 383.94 μg/mL, corroborating the in vivo test. Overall, the results presented here may represent a scientific basis for the traditional use of C. villosus in the treatment of inflammation-related diseases.

Biologic Mechanisms of Macrophage Phenotypes Responding to Infection and the Novel Therapies to Moderate Inflammation.

Pro-inflammatory and anti-inflammatory types are the main phenotypes of the macrophage, which are commonly notified as M1 and M2, respectively. The alteration of macrophage phenotypes and the progression of inflammation are intimately associated; both phenotypes usually coexist throughout the whole inflammation stage, involving the transduction of intracellular signals and the secretion of extracellular cytokines. This paper aims to address the interaction of macrophages and surrounding cells and tissues with inflammation-related diseases and clarify the crosstalk of signal pathways relevant to the phenotypic metamorphosis of macrophages. On these bases, some novel therapeutic methods are proposed for regulating inflammation through monitoring the transition of macrophage phenotypes so as to prevent the negative effects of antibiotic drugs utilized in the long term in the clinic. This information will be quite beneficial for the diagnosis and treatment of inflammation-related diseases like pneumonia and other disorders involving macrophages.

Lipidome remodeling activities of DPA-EA in palmitic acid-stimulated HepG2 cells and the in vivo anti-obesity effect of the DPA-EA and DHA-EA mixture prepared from algae oil.

Background: The nuclear receptor Nur77 has been demonstrated to play a vital role in the inflammatory response and cellular metabolisms, and its ligands exhibit efficacy in the treatment of inflammation-related diseases (e.g., improving mouse acute lung injury (ALI) and obesity. Recently, ω-3 polyunsaturated fatty acid-ethanolamine derivatives (ω-3 PUFA-EAs), including DPA-EA and DHA-EA, have been reported as new Nur77-targeting anti-inflammatory agents. However, the lipid-lowering effect of ω-3 PUFA-EAs is still unknown, and lipid profile changes induced by Nur77-targeting anti-inflammatory agents also remain unclear. Objective: This study aimed to evaluate the lipid-lowering effect and the underlying mechanism of DPA-EA acting as Nur77-targeting anti-inflammatory agents. It also aimed to investigate the in vitro and in vivo lipid-lowering effects of the DPA-EA and DHA-EA mixture prepared from algae oil. Methods: The in vitro lipid-lowing effect of DPA-EA and its mixture with DHA-EA was first evaluated in palmitic acid-stimulated HepG2 Cells. To confirm the lipid-lowering effect and explore the underlying mechanism, we performed untargeted lipidomic analysis using ultra-performance liquid chromatography/triple quadrupole-time-of-flight (TOF) mass spectrometry coupled with multivariate statistical analysis, with another Nur77-targeting anti-inflammatory compound Celastrol (Cel) as a reference. Finally, we examined the anti-obesity effect of the DPA-EA and DHA-EA mixture synthesized from algae oil in a high-fat diet (HFD)-fed mice model. Results: DPA-EA significantly alleviated lipid accumulation with lower toxicity than Celastrol. Nur77-targeting compounds DPA-EA and Celastrol could simultaneously reduce 14 lipids (9 TGs, 2 PCs, 1 PA, 1 SM, and 1 LacCer) and increase 13 lipids (4 DGs, 6 LPEs, 2 PEs, and 1PC) in Pal-stimulated HepG2 cells. However, Cer lipids were more sensitive to DPA-EA, while the over-downregulation of SM lipids might be associated with the off-target toxicity of Celastrol. The mixture of DPA-EA and DHA-EA synthesized from algae oil could significantly decrease TG, TC, and LDL levels and increase HDL levels in HFD-fed mice, exerting an excellent anti-obesity effect. Conclusion: Nur77-targeting anti-inflammatory compound DAP-EA could promote the hydrolysis of PEs and TGs to ameliorate lipid accumulation. The DPA-EA and DHA-EA mixture prepared from algae oil might be a potential therapeutic agent for obesity and other inflammation-related diseases.

Anti-inflammatory phenolics and phenylpropanoids from Praxelis clematidea

Praxelis clematidea (Asteraceae) is a noxious invasive exotic plant in southern China, and it has caused great damage to ecological conditions and serious financial losses. In this study, four new phenolics (1, 2, 7, 8), and two new phenylpropanoids (3, 4), along with seventeen known compounds were separated and purified from the whole plant of P. clematidea. Their chemical structures were determined by extensive spectroscopic analysis methods. Additionally, the potential inhibitory activities on nitric oxide (NO) production and NF-κB nuclear translocation in LPS-triggered RAW 264.7 macrophages of the isolated compounds were evaluated. Notably, compounds 2, 7, and 8 showed significant inhibitory activities on NO production, and also inhibited the expression of iNOS and COX-2. Furthermore, compounds 2, 7, and 8 effectively suppressed the NF-κB nuclear translocation. These findings suggest that P. clematidea has the potential to be developed and promoted as a treatment for inflammation-related diseases.

Engineering core-shell chromium nanozymes with inflammation-suppressing, ROS-scavenging and antibacterial properties for pulpitis treatment.

Oral diseases are usually caused by inflammation and bacterial infection. Reactive oxygen species (ROS), which come from both autologous inflammation tissue and bacterial infection, play an important role in this process. Thus, the elimination of excessive intracellular ROS can be a promising strategy for anti-inflammatory treatment. With the rapid development of nanomedicines, nanozymes, which can maintain the intracellular redox balance and protect cells against oxidative damage, have shown great application prospects in the treatment of inflammation-related diseases. However, their performance in pulpitis and their related mechanisms have yet to be explored. Herein, we prepared dozens of metallic nanoparticles with core-shell structures, and among them, chromium nanoparticles (NanoCr) were selected for their great therapeutic potential for pulpitis disease. NanoCr showed a broad antibacterial spectrum and strong anti-inflammatory function. Antibacterial assays showed that NanoCr could effectively inhibit a variety of common pathogens of oral infection. In vitro experiments offered evidence of the multienzyme activity of NanoCr and its function in suppressing ROS-induced inflammation reactions. The experimental results show that NanoCr has optimal antibacterial and anti-inflammatory properties in in vitro cell models, showing great potential for the treatment of pulpitis. Therefore, the use of NanoCr could become a new therapeutic strategy for clinical pulpitis.

Inflammation-directed nanozyme-eluting hydrogel coating promotes vascular tissue repair by restoring reactive oxygen species homeostasis

Thrombosis and stenosis remain two of the most prevalent complications of vascular implants. The most effective strategy in clinics to inhibit stenosis is based on the eluting of anti-hyperplasia drugs such as sirolimus and everolimus while it also has been known to hinder vascular healing and regeneration. Selectively inhibiting intimal hyperplasia and promoting endothelialization remains a highly challenging target for vascular implants. Due to auto-regenerative antioxidant activity nanoceria as a nanozyme has been widely used to regulate oxidative stress in the treatment of inflammation-related diseases. Yet the application of nanozyme in vascular implants has not hitherto been reported. In this study we constructed a reactive oxygen species (ROS)-targeted nanoceria-eluting degradable zwitterion hydrogel coating on membrane-covered stents with favorable anti-coagulation pro-endothelialization and immunomodulation properties. The hydrogel coating exhibited excellent hemocompatibility and simultaneously promoted the growth of endothelial cells. Nanoceria embedded in hydrogel could be released in response to matrix metalloproteinase (MMP) and effectively scavenge artificial and intracellular ROS via mimicking the activity of natural superoxide dismutase (SOD) and catalase (CAT). In addition the incorporation of nanoceria increased the expression levels of anti-inflammation cytokines and growth factors and reduced the expression levels of pro-inflammation cytokines in macrophages inducing a switch of macrophage phenotype from M1 to M2. The membrane-covered stent based on nanozyme-integrated hydrogel-coated PLLA membrane exhibited a high patency rate and slight intima hyperplasia degree upon implantation into rabbits' iliac arteries/abdominal aortas. This advanced hydrogel coating may provide a new low-cost and drug-free strategy for effectively inhibiting vascular stenosis and promoting vascular repair.

Advances in Fucoxanthin Research for the Prevention and Treatment of Inflammation-Related Diseases.

Owing to its unique structure and properties, fucoxanthin (FX), a carotenoid, has attracted significant attention. There have been numerous studies that demonstrate FX's anti-inflammatory, antioxidant, antitumor, and anti-obesity properties against inflammation-related diseases. There is no consensus, however, regarding the molecular mechanisms underlying this phenomenon. In this review, we summarize the potential health benefits of FX in inflammatory-related diseases, from the perspective of animal and cellular experiments, to provide insights for future research on FX. Previous work in our lab has demonstrated that FX remarkably decreased LPS-induced inflammation and improved survival in septic mice. Further investigation of the activity of FX against a wide range of diseases will require new approaches to uncover its molecular mechanism. This review will provide an outline of the current state of knowledge regarding FX application in the clinical setting and suggest future directions to implement FX as a therapeutic ingredient in pharmaceutical sciences in order to develop it into a treatment strategy against inflammation-associated disorders.

Anti-Inflammatory and Antimicrobial Activities of Portuguese Prunus avium L. (Sweet Cherry) By-Products Extracts.

The bioactivity of natural by-products in food and pharmaceutical applications is the subject of numerous studies. Cherry production and processing generates large amounts of biowaste, most of which is not used. The recovery of these by-products is essential for promoting the circular economy and to improving sustainability in the food industry. In this work, we explored the anti-inflammatory and antimicrobial potential of two different extracts from stems, leaves, and flowers of Portuguese cherries. The anti-inflammatory potential was studied on lipopolysaccharide (LPS)-stimulated mouse macrophages (RAW 264.7) by evaluating the effect of by-products on cellular viability and nitric oxide (NO) production. Disc diffusion and minimum inhibitory concentration (MIC) were used to determine antimicrobial activity. The cherry by-products had no cytotoxic effect on RAW 264.7 cells, and were able to inhibit nitrite production in a dose-dependent manner. Moreover, all aqueous infusions showed good antioxidant activity against NO radicals. Moreover, leaf extracts showed the best activity against most of the strains studied. The results revealed, for the first time, interesting anti-inflammatory and antimicrobial properties of cherry by-products. This could potentially be of interest for their therapeutic use in the treatment of inflammation-related diseases or in controlling the growth of microorganisms.

Dissecting and Evaluating the Therapeutic Targets of Coptis Chinensis Franch in the Treatment of Urinary Tract Infections Induced by Escherichia coli.

Coptis chinensis Franch (CCF) is extensively used in the treatment of inflammatory-related diseases. Accumulating studies have previously demonstrated the anti-inflammatory properties of CCF, yet data on its exact targets against urinary tract infections (UTIs) remain largely unknown. Therefore, the present study decodes the potential targets of action of CCF against UTIs by network pharmacology combined with experiment evaluations. Based on the pharmacology network analysis, the current study yielded six core ingredients: quercetin, palmatine (R)-canadine, berlambine, berberine, and berberrubine. The protein–protein interaction network (PPI) was generated by the string database, and then, four targets (IL6, FOS, MYC, and EGFR) were perceived as the major CCF targets using the CytoNCA plug-in. The results of molecular docking showed that the six core constituents of CCF had strong binding affinities toward the four key targets of UTIs after docking into the crystal structure. The enrichment analysis indicated that the possible regulatory mechanisms of CCF against UTIs were based on the modules of inflammation, immune responses, and apoptosis among others. Experimentally, the Escherichia coli (E. coli) strain CFT073 was applied to establish in vivo and in vitro models. In vivo results revealed that the key targets, IL6 and FOS, are significantly upregulated in rat bladder tissues of UTIs, whereas the expression of MYC and EGFR remained steady. Last, in vitro results further confirmed the therapeutic potential of CCF by reducing the expression of IL6 and FOS. In conclusion, IL6 and FOS were generally upregulated in the progression of E. coli–induced UTIs, whereas the CCF intervention exerted a preventive role in host cells stimulated by E. coli, partially due to inhibiting the expression of IL6 and FOS.

Extracts with anti-inflammatory activities from Acanthopanax trifoliatus (L.) Merr. by inhibiting LPS-induced expression of iNOS and COX-2

Acanthopanax trifoliatus (L.) Merr. have been used as folk medicine to treat various diseases traditionally and the young leaves and shoots of A. trifoliatus are popularly consumed as vegetables and herbal tea in southern China. In the study, we firstly tested the cytotoxicity and NO production of 18 fractions that extracted from the leaves, stems and roots of A. trifoliatus to select the bioactive fraction. The increasing evidence suggested that the dichloromethane extract prepared from stems of A. trifoliatus (ATSDC) have anti-inflammatory activity. Therefore, the study followed to investigate the effects of ATSDC on the inflammatory response and the molecular mechanisms underpinning this effect in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The manuscript showed that ATSDC effectively inhibited NO production in LPS-stimulated cells and significantly reduced the production of pro-inflammatory cytokines IL-6, at a dose of 40 µg/mL, whereas TNF-α production tended to decrease under ATSDC treatment. We also confirmed a dose-dependent and significant inhibition of iNOS and COX-2 protein expression. In conclusion, ATSDC exerted strong inhibitory effect on the expression of iNOS and COX-2 protein in LPS-induced RAW 264.7 macrophages and could be potentially used in treatment of inflammatory-related diseases in the future.

Anti-inflammatory effects of two lupane-type triterpenes from leaves of Acanthopanax gracilistylus on LPS-induced RAW264.7 macrophages

Acanthopanax gracilistylus W.W.Smith (AGS) is an traditional Chinese medicine and its leaves that have rich biological activities has been long used as a fresh vegetable in Chinese folk. There are two lupane-type triterpenoids, 3α,11α-dihydroxy-23-oxo-lup-20(29)-en-28-oic acid (1) and 3α,11α,23-trihydroxy-lup-20(29)-en-28-oic acid (2), were isolated as the active constituents from leaves of AGS. However, the anti-inflammatory effects and potential mechanisms of 1 and 2 on LPS-induced RAW264.7 Macrophages have not been evaluated. In this study, the results shown that compounds 1 and 2 reduced the levels of early pro-inflammatory cytokines TNF-α, IL-1β, the secretion of late pro-inflammatory cytokine HMGB1, as well as the activation of transcription factor NF-κB in RAW 264.7 macrophages induced by LPS. In conclusion, two lupane-type triterpenes (1 and 2) have anti-inflammatory activities in LPS-induced RAW264.7 cells through inhibiting expression of proinflammatory cytokines and NF‐κB activation and could be potentially used in treatment of inflammatory-related diseases in the future.

κ-Carrageenan oligosaccharides induce microglia autophagy through AMPK/ULK1 pathway to regulate their immune response

Microglia are the main effector cells of immune response in central nervous system and are important targets for disease prevention and treatment. Κ-carrageenan Oligosaccharide (KOS), obtained by enzymatic hydrolysis from carrageenan of marine red algae, can inhibit the release of inflammatory factors from the over-activated microglia. The mechanism of microglia autophagy induced by KOS and its relationship with inflammation were studied to explore the development prospect of KOS in the research and treatment of inflammatory related diseases. The effect of KOS on inducing autophagy was detected by the secretion of cytokines by lipopolysaccharide (LPS)-activated microglia, respectively. The protein expression of autophagy-related signaling pathways were detected by Western Blot. The results showed that KOS could significantly protect the microglia from over-activated inflammatory by inducing the autophagy and inhibiting the release of inflammatory cytokines. And KOS could reduce the expression of the protein that related to the AMPK/ULK1 pathways in microglia, so as to regulate the autophagy pathway, and inhibit the inflammatory response of over-activated microglia. The study on the effect of KOS on microglia autophagy and excessive inflammatory response will provide a theoretical basis for further studies on the inhibition of nerve injury by regulating microglia autophagy and inflammatory response.