Croton stipulaceus Kunth, a native Mexican medicinal plant with antioxidant and anti-inflammatory activities / Croton stipulaceus Kunth, planta medicinal mexicana con actividad antioxidante y antiinflamatoria

Leaves of Croton stipulaceuswere extracted (EHex, ECHCl3and EEtOH extracts) to assesstheir antioxidant potential, anti-inflammatory activity in murine models and acute toxicity. EEtOH showed the highest effect in DPPH (37.80% inhibition), FRAP (1065.00 ± 55.30 µmolFe2+) and total polyphenols (231.24 ± 9.05 meq AG/gM). EHex was the most active, ~ 50% inhibition of TPA-induced ear edema; while EEtOH (dose of 2 mg/ear) showed the highest inhibition in the chronic model (97% inhibition), and inhibited MPO activity (48%). In carrageenan-induced edema, ECHCl3(dose 500 mg/kg) was the most active. None of the extracts showed acute toxicity (LD50) at 2 g/kg (p.o.). This work is the first report that supports the traditional use of C. stipulaceusas an anti-inflammatory.

De las hojas de Croton stipulaceusse obtuvieron diferentes extractos (EHex, ECHCl3y EEtOH) evaluando el potencial antioxidante y la actividad antiinflamatoria en modelos murinos y la toxicidad aguda. El EEtOH mostró mayor efecto en DPPH (37.80% inhibición), FRAP (1065.00 ± 55.30 µmolFe2+) y polifenolestotales (231.24 ± 9.05 meq AG/gM). El EHex fue el más activo, cercano al 50% de inhibición del edema auricular inducido con TPA; mientras que el EEtOH (dosis de 2 mg/oreja) mostró la mayor inhibición en el modelo crónico (97% inhibición), e inhibió la actividad de la MPO (48%). En el edema inducido con carragenina, el ECHCl3(dosis 500 mg/kg) fue el más activo. Ninguno de los extractos mostró una toxicidad aguda (DL50) mayor a 2 g/kg (p.o). Este trabajo es el primer reporte que sustenta el uso tradicional de C. stipulaceuscomo antiinflamatorio.

A case report of a gastric ulcer in a 2.5-month-old infant in Syria: Helicobacter pylori and Aspirin as possible causes.

A gastric ulcer is a tear in the stomach lining that manifests as abdominal pain, nausea, vomiting, and weight loss. Its occurrence is lesser in children as compared to adults and its incidence in children ranges between 2% and 8%. Helicobacter pylori and nonsteroidal anti-inflammatory drugs are the most common causes of gastric ulcers. In our case, we report a 2.5-month-old male who presented with severe pallor, hematemesis, and melena with normal weight gain. The patient's mother was infected with COVID-19 a month ago and recovered within 5 days but kept using aspirin and nonsteroidal anti-inflammatory drugs for a month during breastfeeding. An upper gastrointestinal endoscopy revealed a gastric ulcer and the Helicobacter pylori antigen was positive in the biopsy. A COVID-19 infection was detected later in the patient. The patient was administered proton pump inhibitor, clarithromycin, and amoxicillin for Helicobacter pylori antigen and symptomatic treatment for COVID-19. This case report shows that a stomach ulcer can appear in infancy, but opportune interventions such as timely diagnosis and treatment can solve the problem. It also marks the pathophysiological connection between Helicobacter pylori and gastric ulcer.

Elderly Woman With No Autoimmune Disease With Aseptic Meningitis Caused by Celecoxib.

Nonsteroidal anti-inflammatory drug (NSAID)-induced aseptic meningitis (NIAM) is frequently reported in patients with autoimmune disease. Ibuprofen-induced NIAM is the most common case report of NIAM. We report a patient without autoimmune disease who developed NIAM following oral celecoxib administration. A literature review and survey of cases registered in the Japanese Adverse Drug Event Report (JADER) database is also provided. A 73-year-old woman with no autoimmune disease developed a headache the day after taking celecoxib, and NIAM was suspected. The headache resolved quickly following celecoxib discontinuation. Although lumbar puncture was not available in this case, bacterial or viral meningitis was negative, and NIAM could not be ruled out. This case involved an older adult patient without an autoimmune disease, with celecoxib as the causative NSAID. A literature review found numerous cases of autoimmune diseases in younger patients. To date, only one case of celecoxib-induced NIAM has been reported. Analysis of NIAM cases in JADER revealed an onset time of approximately three days. JADER analysis indicated that NIAM tended to occur immediately after administration, although the onset with cyclooxygenase-2 selective agents might be slower.

Dynamic shifts in lung cytokine patterns in post-COVID-19 interstitial lung disease patients: a pilot study.

Introduction: The pathogenesis of post-COVID interstitial lung disease, marked by lung tissue scarring and functional decline, remains largely unknown. Objectives: We aimed to elucidate the temporal cytokine/chemokine changes in bronchoalveolar lavage (BAL) from patients with post-COVID interstitial lung disease to uncover potential immune drivers of pulmonary complications. Design: We evaluated 16 females diagnosed with post-COVID interstitial lung disease, originating from moderate to severe cases during the second epidemic wave in the Autumn of 2020, treated at the Pneumology Department of the Arad County Clinical Hospital, Romania. Their inflammatory response over time was compared to a control group. Methods: A total of 48 BAL samples were collected over three intervals (1, 3, and 6 months) and underwent cytology, gene, and protein expression analyses for pro/anti-inflammatory lung cytokines and chemokines using reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results: One month after infection, there were significant increases in the levels of IL-6 and IL-8. These levels decreased gradually over the course of 6 months but were still higher than those seen in control. Interferon-gamma and tumor necrosis factor alpha exhibited similar patterns. Persistent elevations were found in IL-10, IL-13, and pro-fibrotic M2 macrophages' chemokines (CCL13 and CCL18) for 6 months. Furthermore, pronounced neutrophilia was observed at 1 month post-COVID, highlighting persistent inflammation and lung damage. Neutrophil efferocytosis, aiding inflammation resolution and tissue repair, was evident at the 1-month time interval. A notable time-dependent reduction in CD28 was also noticed. Conclusion: Our research provides insight into the immunological processes that may lead to the fibrotic changes noted in the lungs following COVID-19.

BACKGROUND: Post-COVID lung disease represents a significant health concern that demands comprehensive research. The pathogenesis of post-COVID interstitial lung disease, marked by lung tissue scarring and functional decline, remains largely unknown. METHODS: We evaluated 16 females diagnosed with post-COVID interstitial lung disease, originating from moderate to severe cases during the second epidemic wave in the Autumn 2020, treated at the Pneumology Department of the Arad County Clinical Hospital, Romania. Their inflammatory response over time was compared to a control group. A total of 48 BAL samples were collected over three intervals (1, 3, and 6 months) and underwent cytology, gene, and protein expression analyses for pro/anti-inflammatory lung cytokines and chemokines using RT-PCR and ELISA The interrelationships between the expression levels of various pro-inflammatory and anti-inflammatory cytokines and chemokines by Pearson's correlations was investigated. RESULTS: One month after infection, there were significant increases in the levels of IL-6 and IL-8. These levels decreased gradually over the course of six months but were still higher than those seen in control. IFN-γ and TNF-α exhibited similar patterns. Persistent elevations were found in IL-10, IL-13, and pro-fibrotic M2 macrophages' chemokines (CCL13 and CCL18) for six months. Pronounced neutrophilia was observed at 1 month post-COVID, highlighting persistent inflammation and lung damage. Neutrophils efferocytosis, aiding inflammation resolution and tissue repair, was evident at the 1-month time-interval. A notable time-dependent reduction in CD28 was also noticed. CONCLUSIONS: Our research provides insight into the immunological processes that may lead to the fibrotic changes noted in the lungs following COVID-19.

Dynamic shifts in lung cytokine patterns in post-COVID-19 interstitial lung disease patients: a pilot study The objective of this pilot study was to investigate changes in lung cytokine pro- and anti-inflammatory profiles among patients with interstitial lung disease after COVID-19 infection.

Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticancer and antiinflammatory agents.

Introduction: Cancer, a significant global health concern, necessitates innovative treatments. The pivotal role of chronic inflammation in cancer development underscores the urgency for novel therapeutic strategies. Benzothiazole derivatives exhibit promise due to their distinctive structures and broad spectrum of biological effects. This study aims to explore new anti-tumor small molecule drugs that simultaneously anti-inflammatory and anticancer based on the advantages of benzothiazole frameworks. Methods: The compounds were characterized by nuclear magnetic resonance (NMR), liquid chromatograph-mass spectrometer (LC-MS) and high performance liquid chromatography (HPLC) for structure as well as purity and other related physicochemical properties. The effects of the compounds on the proliferation of human epidermoid carcinoma cell line (A431) and human non-small cell lung cancer cell lines (A549, H1299) were evaluated by MTT method. The effect of compounds on the expression levels of inflammatory factors IL-6 and TNF-α in mouse monocyte macrophages (RAW264.7) was assessed using enzyme-linked immunosorbent assay (ELISA). The effect of compounds on apoptosis and cell cycle of A431 and A549 cells was evaluated by flow cytometry. The effect of compounds on A431 and A549 cell migration was evaluated by scratch wound healing assay. The effect of compounds on protein expression levels in A431 and A549 cells was assessed by Western Blot assay. The physicochemical parameters, pharmacokinetic properties, toxicity and drug similarity of the active compound were predicted using Swiss ADME and admetSAR web servers. Results: Twenty-five novel benzothiazole compounds were designed and synthesized, with their structures confirmed through spectrogram verification. The active compound 6-chloro-N-(4-nitrobenzyl) benzo[d] thiazol-2-amine (compound B7) was screened through a series of bioactivity assessments, which significantly inhibited the proliferation of A431, A549 and H1299 cancer cells, decreased the activity of IL-6 and TNF-α, and hindered cell migration. In addition, at concentrations of 1, 2, and 4 µM, B7 exhibited apoptosis-promoting and cell cycle-arresting effects similar to those of the lead compound 7-chloro-N-(2, 6-dichlorophenyl) benzo[d] thiazole-2-amine (compound 4i). Western blot analysis confirmed that B7 inhibited both AKT and ERK signaling pathways in A431 and A549 cells. The prediction results of ADMET indicated that B7 had good drug properties. Discussion: This study has innovatively developed a series of benzothiazole derivatives, with a focus on compound B7 due to its notable dual anticancer and anti-inflammatory activities. B7 stands out for its ability to significantly reduce cancer cell proliferation in A431, A549, and H1299 cell lines and lower the levels of inflammatory cytokines IL-6 and TNF-α. These results position B7B7 as a promising candidate for dual-action cancer therapy. The study's mechanistic exploration, highlighting B7's simultaneous inhibition of the AKT and ERK pathways, offers a novel strategy for addressing both the survival mechanisms of tumor cells and the inflammatory milieu facilitating cancer progression.

Chemical composition and biological activities of the Algerian Cymbalaria muralis aerial parts.

In the present study we report data about antioxidant (DPPH, ß-Carotene, reducing power), anti-inflammatory (xylene-induced ear oedema in mice (76 ± 1.0%) and membrane stabilisation (100%)) and antimicrobial (Escherichia coli ATCC25922, Staphylococcus aureus ATCC25923, Pseudomonas arugenosa ATCC27853 and Fusarium oxysporum ATCC62506) activities of the ethanolic extract from the Algerian Cymbalaria muralis P. Gaertn., B. Mey. & Scherb (CME). The LC-ESIMS analysis of CME chemical profile allowed to identify antirrhinoside (1), catalpol (2), linarioside (3), glucosyringic acid (4), angoroside C (5), apigenin 7-O-glucoside (6), acacetin 7-O-ß-D-glucopyranoside (7), apigenin (8), chrysoeriol 7-rutinoside (9), diosmin (10) and linarin (11). The evaluated total phenolic and flavonoid contents support the biological activities.

A new 3,4-dihydroisocoumarin and an antiinflammatory coumarin from the roots of Saposhnikovia divaricata (Turcz.) Schischk.

Phytochemical investigation of the roots of Saposhnikovia divaricata (Turcz.) Schischk resulted in the isolation of twelve coumarin derivatives including one new 3,4-dihydroisocoumarin (1) and eleven known 3,4-unsubstituted coumarins (2-12). Structural elucidation of compounds 1-12 was established by 1D and 2D NMR spectra referring to the literature, together with high-resolution mass spectrometric analysis. LPS-induced RAW264.7 inflammatory cell model was used to determine the potential antiinflammation activity of all the isolated compounds in vitro. The results showed that compound 3 significantly inhibited the production of lipopolysaccharide (LPS)-induced NO in macrophages (IC50 = 4.54 ± 1.71 µM), more active than the positive control (L-NMMA).

STING-Pathway Inhibiting Nanoparticles (SPINs) as a Platform for Treatment of Inflammatory Diseases.

Aberrant activation of the cyclic GMP-AMP synthase (cGAS)/Stimulator of Interferon Genes (STING) pathway has been implicated in the development and progression of a myriad of inflammatory diseases including colitis, nonalcoholic steatohepatitis, amyotrophic lateral sclerosis (ALS), and age-related macular degeneration. Thus, STING pathway inhibitors could have therapeutic application in many of these inflammatory conditions. The cGAS inhibitor RU.521 and the STING inhibitor H-151 have shown promise as therapeutics in mouse models of colitis, ALS, and more. However, these agents require frequent high-dose intraperitoneal injections, which may limit translatability. Furthermore, long-term use of systemically administered cGAS/STING inhibitors may leave patients vulnerable to viral infections and cancer. Thus, localized or targeted inhibition of the cGAS/STING pathway may be an attractive, broadly applicable treatment for a variety of STING pathway-driven ailments. Here we describe STING-Pathway Inhibiting Nanoparticles (SPINS)-poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with RU.521 and H-151-as a platform for enhanced and sustained inhibition of cGAS/STING signaling. We demonstrate that SPINs are equally or more effective at inhibiting type-I interferon responses induced by cytosolic DNA than free H-151 or RU.521. Additionally, we describe a SPIN formulation in which PLGA is coemulsified with poly(benzoyloxypropyl methacrylamide) (P(HPMA-Bz)), which significantly improves drug loading and allows for tunable release of H-151 over a period of days to over a week by varying P(HPMA-Bz) content. Finally, we find that all SPIN formulations were as potent or more potent in inhibiting cGAS/STING signaling in primary murine macrophages, resulting in decreased expression of inflammatory M1-like macrophage markers. Therefore, our study provides an in vitro proof-of-concept for nanoparticle delivery of STING pathway inhibitors and positions SPINs as a potential platform for slowing or reversing the onset or progression of cGAS/STING-driven inflammatory conditions.

Oxomollugin, an oxidized substance in mollugin, inhibited LPS-induced NF-κB activation via the suppressive effects on essential activation factors of TLR4 signaling.

Oxomollugin is a degraded product of mollugin and was found to be an active compound that inhibits LPS-induced NF-κB activation. In this study, we investigated the inhibitory activity of oxomollugin, focusing on TLR4 signaling pathway, resulting in NF-κB activation. Oxomollugin inhibited the LPS-induced association of essential factors for initial activation of TLR4 signaling, MyD88, IRAK4 and TRAF6. Furthermore, oxomollugin showed suppressive effects on LPS-induced modification of IRAK1, IRAK2 and TRAF6, LPS-induced association of TRAF6-TAK1/TAB2, and followed by IKKα/ß phosphorylation, which critical in signal transduction leading to LPS-induced NF-κB activation. The consistent results suggested that oxomollugin inhibits LPS-induced NF-κB activation via the suppression against signal transduction in TLR4 signaling pathway.The activities of oxomollugin reported in this study provides a deeper understanding on biological activity of mollugin derivatives as anti-inflammatory compounds.

A novel neuroimmune modulation system for the treatment of rheumatoid arthritis.

The vagus nerve has an anti-inflammatory effect through the inflammatory reflex, which inhibits the release of proinflammatory cytokines by macrophages. Recent pilot clinical trials, using implantable bioelectronic devices, have demonstrated the efficacy of vagus nerve stimulation in adult patients with rheumatoid arthritis and inflammatory bowel diseases as an alternative to drugs, which are not devoid of side effects and are costly. In this issue of Bioelectronic Medicine, Peterson et al. report the safety of novel implantable neuroimmune modulation device for treating rheumatoid arthritis (The RESET RA study), which I will discuss in this commentary.

Three new pterosins from Pteris semipinnata.

Three new pterosins, named as semipterosin A (1), B (2) and C (3), together with 11 known pterosins (4-14), were isolated from the aerial parts of Pteris semipinnata. Their structures were elucidated by HRESI-MS, NMR spectral data, CD and literature comparisons. Three new pterosins were assessed for their anti-inflammatory activity. Compounds 1-3 inhibited the NF-kB induction by 40.7%, 61.9% and 34.0%, respectively. This is the first report of the isolation of compounds 6-14 from this plant.

Anti-inflammatory steroids from the South China Sea Sponge Spongia officinalis.

One new highly degraded steroid, namely 21-nor-4-ene-chaxine A (1) furnishing a 5/6/5-tricyclic, along with one known related analogue (2), were isolated from the South China Sea sponge Spongia officinalis. Their structures including absolute configurations were established by extensive spectroscopic data analysis, TDDFT-ECD calculation, and comparison with the spectral data previously reported in the literature. Compound 1 represent the new member of incisterols family with a highly degradation in ring B. In vitro bioassays revealed compound 2 exhibited significant anti-microglial inflammatory effect on lipopolysaccharide (LPS)-induced inflammation in BV-2 microglial cells.

Neutrophil extracellular trap formation and its implications in nonsteroidal anti-inflammatory drug-induced small intestinal injury.

BACKGROUND AND AIM: Nonsteroidal anti-inflammatory drugs (NSAIDs) damage the small intestine via neutrophil infiltration driven by the mucosal invasion of enterobacteria. The antimicrobial function of neutrophils is partially dependent on neutrophil extracellular traps (NETs). Excessive NET formation has been associated with several inflammatory diseases. Here, we aimed to investigate the role of NETs in NSAID-induced small intestinal damage using human samples and an experimental mouse model. METHODS: Human small intestine specimens were obtained from NSAID users during double-balloon enteroscopy. Wild-type, protein arginine deiminase 4 (PAD4) knockout, and antibiotic-treated mice were administered indomethacin to induce small intestinal injury. The expression of NET-associated proteins, including PAD4, citrullinated histone H3 (CitH3), cell-free DNA, and myeloperoxidase (MPO), was evaluated. RESULTS: The double-positive stained area with CitH3 and MPO, which is specific for neutrophil-derived extracellular traps, was significantly high in the injured small intestinal mucosa of NSAID users. In a mouse model, small intestinal damage developed at 6 h after indomethacin administration, accompanied by increased mRNA levels of interleukin-1ß and keratinocyte chemoattractant and elevated NET-associated protein levels of PAD4, CitH3, and MPO in small intestine and serum levels of cell-free DNA. Both genetic deletion and pharmacological inhibition of PAD4 attenuated this damage by reducing the mRNA expression of inflammatory cytokines and NET-associated proteins. Furthermore, mice pretreated with antibiotics showed resistance to indomethacin-induced small intestinal damage, with less NET formation. CONCLUSION: These results suggest that NETs aggravate NSAID-induced small intestinal injury. Therefore, NET inhibition could be a potential treatment for NSAID-induced small intestinal injury.

Multifaceted role of inosine in complex diseases and human health.

Purines are chemical compounds integral to health and are crucial for the synthesis of nucleic acids. They are part of DNA and RNA and participate in various metabolic and signaling processes. They also function as neurotransmitters and serve as co-substrates for activating many metabolites. Inosine, a purine nucleoside, is a breakdown product of adenosine with similar properties and a much longer half-life (15 h vs ∼5 s) than adenosine. The purpose of this narrative review is to discuss the metabolic effects of inosine and highlight its beneficial properties and implication in complex diseases such as obesity, type 2 diabetes, cancers, cardiovascular diseases, and neurodegenerative diseases. A search was performed for purine- and inosine-related articles on the University of North Carolina (UNC) Health Sciences Library, PubMed, and Google Scholar sites. Inosine is involved in the regulation of RNA editing, metabolic enzyme activity, and signaling pathways. Animal and cell culture studies have shown inosine to be anti-inflammatory, immunomodulatory, and neuroprotective, and serving as a critical regulator of immune checkpoint inhibition therapeutic response in various tumor types. Recent studies have also implicated inosine in increasing energy expenditure, browning of adipose tissue, and improving leptin sensitivity. Human studies, however, have been limited to urate-elevating properties of inosine. These findings make inosine relevant to many complex diseases, and need to be translated to humans. Future studies should be conducted to investigate the mechanisms underlying the role of inosine in adiposity, inflammation, oxidative stress, and neuronal function.

Histological and biochemical changes in a rat rotator cuff tear model with or without the subacromial bursa.

The subacromial bursa (SAB) plays an important role in the tendon healing process. Based on previous reports, co-culture of the rotator cuff (RC) and SAB have been shown to increase the tendon-related gene expressions, inflammatory cytokines, and tensile strength. However, the nature of the specific biochemical alterations during the inflammatory and repair phases of tendon healing with or without the SAB remain unknown. Using a full-thickness RC tear rat model, we determined how the presence or absence of the SAB alters the histological characteristics and gene expressions. After 3 and 6 weeks, tissues were collected for histological and real-time quantitative polymerase chain reaction (RT-qPCR) evaluations. Results showed greater cell density at 3 weeks, neovascularization and tendon thickening at 6 weeks with SAB preservation. Immunostaining revealed significant increases in type 3 collagen (COL3) expression at 6 weeks with SAB preservation. The RT-qPCR results showed that SAB preservation induced significant increases in the expression of scleraxis, matrix metalloproteinase-13 (MMP-13), interleukin-1ß (IL-1ß), and inducible nitric oxide synthase (iNOS) at 3 weeks and significant increases in COL3, IL-10, and arginase-1 (Arg-1) at 6 weeks. An RC tear undergoes more appropriate inflammatory and repair phases during the tendon healing process when the SAB is retained.

Synthesis, physicochemical characterization, and investigation of anti-inflammatory activity of water-soluble PEGylated 1,2,4-Triazoles.

A series of water-soluble PEGylated 1,2,4-triazoles 5-8 were successfully synthesized from methyl 5-(chloromethyl)-1-aryl-1H-1,2,4-triazole-3-carboxylates 1. All of the water-soluble PEGylated 1,2,4-triazoles were characterized by FT-IR and 1H NMR spectroscopy. The solubility, in vitro plasma stability, and anti-inflammatory activity were also determined and compared to original methyl 5-(halomethyl)-1-aryl-1H-1,2,4-triazole-3-carboxylates. For SAR study, all PEGylated 1,2,4-triazoles 5-8 performed potential anti-inflammatory activity on LPS-induced RAW 264.7 cells (IC50 = 3.42-7.81 µM). Moreover, the western blot result showed PEGylated 1,2,4-triazole 7d performed 5.43 and 2.37 folds inhibitory activity over iNOS and COX-2 expressions. On the other hand, the cell viability study revealed PEGylated 1,2,4-triazoles 7 and 8 with PEG molecular weight more than 600 presented better cell safety (cell viability > 95 %). Through the solubility and in vitro plasma stability studies, PEGylated 1,2,4-triazoles 7a-d exhibited higher hydrophilicity and prolonged 2.01 folds of half-life in compound 7d. Furthermore, the in vivo anti-inflammatory and gastric safety results indicated PEGylated 1,2,4-triazole 7d more effectively decreased the inflammatory response in edema and COX-2 expression and exhibited higher gastric safety than Indomethacin. Following the in vitro and in vivo study results, PEGylated 1,2,4-triazole 7d possessed favorable solubility, plasma stability features, safety, and significant anti-inflammatory activity to become the potential water-soluble anti-inflammatory candidate.

Triterpene esters of cirsium setosum and their anti-inflammatory activity.

Two new triterpene fatty acid esters, 3ß-palmityloxy-12,27-cyclofriedoolean-14-en-11α-ol (1) and 3ß-palmityloxy-19α-hydroxyursane (2), together with 3ß-hydroxy-11-oxo-olean-12-enyl palmitate (3) were isolated from the potent anti-inflammatory active fraction of the petroleum ether-soluble part of Cirsium setosum ethanol extract. Compound 1 was found to be a rare 12,27-cyclopropane triterpenoid. Their structures were determined through spectral data analysis combined with literature reports. Furthermore, in vitro experiment, compounds 1-3 exhibited significant inhibitory effects on nitric oxide production in lipopolysaccharide-activated mouse RAW264.7 macrophages.

Mechanistic insights into anti-inflammatory and immunosuppressive effects of plant secondary metabolites and their therapeutic potential for rheumatoid arthritis.

The anti-inflammatory and immunosuppressive activities of plant secondary metabolites are due to their diverse mechanisms of action against multifarious molecular targets such as modulation of the complex immune system associated with rheumatoid arthritis (RA). This review discussed and critically analyzed the potent anti-inflammatory and immunosuppressive effects of several phytochemicals and their underlying mechanisms in association with RA in experimental studies, including preliminary clinical studies of some of them. A wide range of phytochemicals including phenols, flavonoids, chalcones, xanthones, terpenoids, alkaloids, and glycosides have shown significant immunosuppressive and anti-inflammatory activities in experimental RA models and a few have undergone clinical trials for their efficacy and safety in reducing RA symptoms and improve patient outcomes. These phytochemicals have potential as safer alternatives to the existing drugs in the management of RA, which possess a wide range of serious side effects. Sufficient preclinical studies on safety and efficacy of these phytochemicals must be performed prior to proper clinical studies. Further studies are needed to address the barriers that have so far limited their human use before the therapeutic potential of these plant-based chemicals as anti-arthritic agents in the treatment of RA is fully realized.

Anti-Inflammatory Salicin Derivatives from the Barks of Salix tetrasperma.

The genus Salix L. is traditionally used in folk medicine to alleviate pain caused by various kinds of inflammation. In the present study, 10 undescribed salicin derivatives along with 5 known congeners were isolated from the barks of Salix tetrasperma, and their structures were elucidated by spectroscopic analyses, single-crystal X-ray diffraction, electronic circular dichroism (ECD) calculations, and chemical conversions. Compounds 4-6 significantly inhibited NO production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, and the most active 4 obviously suppressed the production of IL-1ß and IL-6 and decreased iNOS and COX-2 expression in a dose-dependent manner. Further Western blotting analysis revealed that the anti-inflammatory mechanism of 4 is possibly mediated through the MAPK and NF-κB signaling pathways.

Four new tirucallane-type triterpenoids from Aphanamixis polystachya.

Four new tirucallane-type triterpenoids, polystanins H-K (1-4), were obtained from the stems and leaves of Aphanamixis polystachya. Their structures were elucidated by analysis of the spectroscopic data and comparison with literature data. Compounds 1 and 2 showed week inhibitory effects against NO production in LPS-stimulated RAW264.7 cells. All the isolates were investigated for their antifungal activities against drug-resistant Candida albicans.