Zingiber officinale Root Capsule Extract Synergistically Enhance the Anti-Inflammatory Effects of Diclofenac Sodium in Experimental Acute Inflammation.

The present study aimed to evaluate the anti-inflammatory effects of ginger (Zingiber officinale) root capsule extract (GRCE) in doses of 100 mg/kg b.w. (body weight) and 200 mg/kg b.w. alone and in combination with a low dose (5 mg/kg b.w.) of diclofenac sodium (D) on carrageenan-induced acute inflammation (AI). The association of GRCE in a dose of 200 mg/kg b.w. with D offered the highest inhibition percentage for edema, reaching the maximum level of inhibition (95%) after 24 h. The association of GRCE in a dose of 200 mg/kg b.w. with D showed the ability to reduce tissue inflammatory changes when compared to D alone, while GRCE alone did not exhibit such properties. The association of both doses of GRCE with D showed significantly lower plasma and tissue levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) by up to 55% (p ≤ 0.0317), with the best results obtained by the group who received GRCE in the higher dose. These associations reduced the serum and tissue levels of prostaglandin-endoperoxide synthase 2 (COX-2) by up to 71% (p ≤ 0.0371). In conclusion, the association of GRCE with a low dose of D could be an appropriate combination to decrease the dose used to reduce serum and tissue levels of inflammatory molecules, edema, and histological changes in acute inflammation. Further research will be necessary to achieve clinical evaluation.

Essential Oils from the Genus Piper Promote Antinociception by Modulating TRP Channels and Anti-Inflammatory Effects in Adult Zebrafish.

The Piper genus, known for its pharmacological potential, comprises 2,263 species primarily found in tropical regions. Despite recent advancements in pain therapies, the demand for more effective and well-tolerated analgesics and anti-inflammatories, particularly for chronic pain, remains. This study assessed the effects of essential oils from Piper caldense, Piper mosenii, and Piper mikanianum on nociceptive behavior induced by formalin and capsaicin, as well as their anti-inflammatory impact induced by carrageenan, using adult zebrafish models. Results indicated non-toxic essential oils with antinociceptive properties in both neurogenic and inflammatory phases of formalin-induced nociception through interaction with the TRPA1 receptor. Additionally, P. mosenii essential oil also blocked the nociceptive effect of capsaicin, a TRPV1 receptor agonist. Furthermore, essential oils from P. caldense and P. mikanianum exhibited significant anti-inflammatory effects by reducing carrageenan-induced abdominal edema. These findings highlight the pharmacological potential of Piper's essential oils as antinociceptive and anti-inflammatory agents.

Ethanol extract of Paridis rhizoma attenuates carrageenan-induced paw swelling in rats by inhibiting the production of inflammatory factors.

CONTEXT: Inflammation has been identified as a key factor contributing to the development of numerous diseases. Several anti-inflammatory drugs have been developed to treat inflammation-related diseases. However, some of such drugs are associated with varying degrees of side effects. Therefore, it is imperative to develop new anti-inflammatory drugs with reducing side effects for the treatment of inflammation-related diseases. Natural anti-inflammatory drugs have emerged as an important area of research in recent years. The study was to determine the anti-inflammatory mechanism of Paridis rhizoma extract (PRE) in rat models of acute inflammation induced by carrageenan and RAW264.7 cells models induced by lipopolysaccharide (LPS). MATERIALS AND METHODS: PRE was investigated using the carrageenan-induced paw oedema model on rats in vivo. Histopathology examined the extent of inflammatory infiltration and tissue damage. The effect of PRE on the levels of specific cytokines was determined using enzyme-linked immunosorbent assay (ELISA). The Cell Counting Kit (CCK)-8 assay evaluated the cytotoxic effects of PRE on Raw264.7 cells. The mRNA expression levels of cytokines were quantified using quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). Western blot measured TNF-α, IL6, TLR4, p-P65, p-IKB, HO1, SOD1 and SOD2. Fluorescence measured the cellular levels of reactive oxygen species (ROS). RESULTS: PRE treatment reduced interstitial edema and structural damage in a dose-dependent manner in vivo. PRE inhibited inflammatory responses in vivo and in vitro, as evidenced by the decreased expression of inflammatory factors, production of ROS, and increased expression of SOD1, SOD2, and HO1. Moreover, PRE inhibited the activity of the nuclear factor kappa B (NF-kB) pathway. CONCLUSION: The anti-inflammatory activity and potential mechanism of PRE were demonstrated according to the results. PRE reduced LPS-induced inflammation in RAW264.7 cells by inhibiting the NF-KB signaling pathway and ROS production in vitro. PRE alleviated interstitial edema and structural damage in the carrageenan-induced paw edema model on rats in vivo. This study provided an idea for future development of PR-based anti-inflammatory drugs.

Antarctic Krill Oil from Euphausia superba Ameliorates Carrageenan-Induced Thrombosis in a Mouse Model.

FJH-KO obtained from Antarctic krill, especially Euphausia superba, has been reported to contain high amounts of omega-3 polyunsaturated fatty acids (n-3 PUFA) and to exhibit anticancer and anti-inflammatory properties. However, its antithrombotic effects have not yet been reported. This study aimed to investigate the antithrombotic effects of FJH-KO in carrageenan-induced thrombosis mouse models and human endothelial cells. Thrombosis was induced by carrageenan injection, whereas the mice received FJH-KO pretreatment. FJH-KO attenuated carrageenan-induced thrombus formation in mouse tissue vessels and prolonged tail bleeding. The inhibitory effect of FJH-KO was associated with decreased plasma levels of thromboxane B2, P-selectin, endothelin-1, ß-thromboglobulin, platelet factor 4, serotonin, TNF-α, IL-1ß, and IL-6. Meanwhile, FJH-KO induced plasma levels of prostacyclin I2 and plasminogen. In vitro, FJH-KO decreased the adhesion of THP-1 monocytes to human endothelial cells stimulated by TNF-α via eNOS activation and NO production. Furthermore, FJH-KO inhibited the expression of TNF-α-induced adhesion molecules such as ICAM-1 and VCAM-1 by suppressing the NF-κB signaling pathway. Taken together, our study demonstrates that FJH-KO protects against carrageenan-induced thrombosis by regulating endothelial cell activation and has potential as an antithrombotic agent.

Radical Scavenging, Anti-Inflammatory, and Hepatoprotective Activities of Pentacyclic Triterpene isolated from Rosa webbiana.

INTRODUCTION: Rosa webbiana (RW) Wall Ex. Royle is used in traditional medicine in Pakistan for the treatment of several diseases including jaundice. To date, only neuroprotective potential of the plant has been evaluated. OBJECTIVE: The current study was designed to isolate bioactive compound(s) and investigate its possible radical scavenging, anti-inflammatory and hepatoprotective activities. METHODS: Column chromatography was done to isolate compounds from the chloroform fraction of RW. The compound was characterized by mass spectrometry, 1H-NMR, and 2D-NMR spectroscopy. Radical scavenging activity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H2O2) assays, while anti-inflammatory potential was evaluated via xylene-induced ear edema and carrageenan-induced paw edema models. For hepatoprotection, CCl4-induced model in mice was used. RESULTS: A triterpene compound (3α, 21ß-dihydroxy-olean-12-ene) was isolated from RW fruits (ARW1). The compound exhibited DPPH and H2O2 scavenging activities 61 ± 1.31% and 66 ± 0.48% respectively at 500 µg/ml. ARW1 (at 50 mg/kg) exhibited 62.9 ± 0.15% inhibition of xylene-induced ear edema and 66.6 ± 0.17% carrageenan-induced paw edema in mice. In CCl4-induced hepatotoxic mice, ARW1 significantly countered elevation in alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (T.B), and reduction in total protein (T.P) levels. Liver histomorphological study supported the serum biochemical profile for hepatoprotection. Moreover, ARW1 significantly attenuated the toxic changes in body and liver weight induced by CCl4. CONCLUSION: The compound ARW1 exhibited anti-radical, anti-inflammatory and hepatoprotective effects. The anti-inflammatory and hepatoprotective activities may be attributed to anti-oxidant potential of the compound.

Antiedematogenic and Analgesic Activities of Abietic Acid in Mice.

Exacerbated inflammatory responses to harmful stimuli can lead to significant pain, edema, and other complications that require pharmacological intervention. Abietic acid (AA) is a diterpene found as a significant constituent in pine species, and evidence has identified its biological potential. The present study aimed to evaluate abietic acid's antiedematogenic and anti-inflammatory activity in mice. Swiss mice (Mus musculus) weighing 20-30 g were treated with AA at 50, 100, and 200 mg/kg. The central nervous system (CNS) effects were evaluated using open-field and rotarod assays. The antinociceptive and anti-inflammatory screening was assessed by the acetic acid and formalin tests. The antiedematogenic activity was investigated by measuring paw edema induced by carrageenan, dextran, histamine, arachidonic acid, and prostaglandin, in addition to using a granuloma model. The oral administration of abietic acid (200 mg/Kg) showed no evidence of CNS effects. The compound also exhibited significant antiedematogenic and anti-inflammatory activities in the carrageenan and dextran models, mostly related to the inhibition of myeloperoxidase (MOP) activity and histamine action and, to a lesser extent, the inhibition of eicosanoid-dependent pathways. In the granuloma model, abietic acid's effect was less expressive than in the acute models investigated in this study. In conclusion, abietic acid has analgesic and antiedematogenic activities related to anti-inflammatory mechanisms.

Antioxidant Activity of a Sicilian Almond Skin Extract Using In Vitro and In Vivo Models.

Almond skins are known for their antioxidative and anti-inflammatory properties, which are mainly due to the presence of polyphenols. The aim of the present study was to evaluate the antioxidant and anti-inflammatory effects of almond skin extract (ASE) obtained from the Sicilian cultivar "Fascionello" and to evaluate the possible mechanisms of action using an in vitro model of human monocytic U937 cells as well as an in vivo model of carrageenan (CAR)-induced paw edema. The in vitro studies demonstrated that pretreatment with ASE inhibited the formation of ROS and apoptosis. The in vivo studies showed that ASE restored the CAR-induced tissue changes; restored the activity of endogenous antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione; and decreased neutrophil infiltration, lipid peroxidation, and the release of proinflammatory mediators. The anti-inflammatory and antioxidant effects of ASE could be associated with the inhibition of the pro-inflammatory nuclear NF-κB and the activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2) antioxidant pathways. In conclusion, almond skin could reduce the levels of inflammation and oxidative stress and could be beneficial in the treatment of several disorders.

Gut Protective Effect from D-Methionine or Butyric Acid against DSS and Carrageenan-Induced Ulcerative Colitis.

Microbiome dysbiosis resulting in altered metabolite profiles may be associated with certain diseases, including inflammatory bowel diseases (IBD), which are characterized by active intestinal inflammation. Several studies have indicated the beneficial anti-inflammatory effect of metabolites from gut microbiota, such as short-chain fatty acids (SCFAs) and/or D-amino acids in IBD therapy, through orally administered dietary supplements. In the present study, the potential gut protective effects of d-methionine (D-Met) and/or butyric acid (BA) have been investigated in an IBD mouse model. We have also built an IBD mouse model, which was cost-effectively induced with low molecular weight DSS and kappa-carrageenan. Our findings revealed that D-Met and/or BA supplementation resulted in the attenuation of the disease condition as well as the suppression of several inflammation-related gene expressions in the IBD mouse model. The data shown here may suggest a promising therapeutic potential for improving symptoms of gut inflammation with an impact on IBD therapy. However, molecular metabolisms need to be further explored.

Anti-Inflammatory Effect of Izalpinin Derived from Chromolaena leivensis: λ-Carrageenan-Induced Paw Edema and In Silico Model.

The flavonoid izalpinin was isolated from the aerial parts of Chromolaena leivensis. Its structural determination was carried out using MS and NMR spectroscopic techniques (1H, 13C). This compound was evaluated for its anti-inflammatory effect in a rat model on λ-carrageenan-induced plantar edema. Paw inflammation was measured at one-hour intervals for seven hours following the administration of λ-carrageenan. Serum creatine kinase (CK) levels were evaluated, obtaining statistically significant results with the treatments at doses of 10 mg/kg (* p < 0.01) and 20 mg/kg (** p < 0.005). The anti-inflammatory effect of the compound was evaluated by using plethysmography, and the results showed significant differences at the three concentrations (10 mg/kg, 20 mg/kg, 40 mg/kg) in the first and third hours after treatment. * p < 0.05; ** p < 0.001; **** p < 0.0001 vs. the negative control group treated with vehicle (DMSO). Lastly, molecular docking analyses reveal that izalpinin has a strong binding affinity with five target proteins involved in the inflammatory process. The analysis using molecular dynamics allowed demonstrating that the ligand-protein complexes present acceptable stability, with RMSD values within the allowed range.

The inhibitory potential of chemical constituents of Ficus carica targeting interleukin-6 (IL-6) mediated inflammation.

Inflammation is an innate reaction of the body of an individual when subjected to the noxious factors repeatedly. Pharmacological approaches focused at disrupting cytokine signaling networks have become significant therapeutic alternatives for the treatment of inflammatory illnesses, cancer and autoimmune disorders. High levels of inflammatory mediators, particularly interleukin IL-1, IL-6, IL-18, IL-12, and tumor necrosis factor alpha leads to a cytokine storm in the body. Among all the released cytokines in a patient suffering from inflammatory disorder, IL-6 mediator has a pivotal role in this inflammatory cascade which progresses to a cytokine storm. Therefore, the blockage of the IL-6 inflammatory mediator could be a promising treatment option for the patients with hyper inflammatory conditions. The phytochemicals could provide the new lead compounds against the IL-6 mediator. Ficus carica has been the ideal plant of research and investigation due to its commercial, economic and medical importance. The anti-inflammatory properties of F. carica were further investigated by in silico and in vivo approaches. The docking scores of Cyanidin-3,5-diglucoside, Kaempferol-7-O-rutinoside, Cyanidin-3-rhamnoglucoside, and Rutin are -9.231, -8.921, -8.840, and -8.335 Kcal/mole respectively. The free energy of binding and stability of the docked complexes of these top four phytochemicals with the IL-6 were further analyzed by Molecular Mechanics-Generalized Born Surface Area and Molecular Dynamic simulations, respectively. The in vivo anti-inflammatory carrageenan-induced rat paw edema model was used for the validation of in silico results. The maximum percentage paw edema inhibition with petroleum ether and ethyl acetate was 70.32% and 45.05%, respectively. The in vivo anti-inflammatory activity confirms the anti-inflammatory potential of F. carica. Therefore, it is predicted that Cyanidin-3,5-diglucoside, Kaempferol-7-O-rutinoside, Cyanidin-3-rhamnoglucoside, and Rutin have the potential to inhibit the IL-6 mediator which will aid in mitigating the cytokine storm in patients with acute inflammations.

Anti-inflammatory, Antinociceptive, and Toxicological Properties of Uvaria comperei Stem Crude Extract and Fractions.

The present study was carried out to investigate the anti-inflammatory activity of a methanolic extract and fractions of Uvaria comperei stems. The crude extract was obtained by maceration of the powder in methanol and fractions by vacuum chromatography from the methanolic extract. To study the anti-inflammatory activity in vitro, red blood cell lysis inhibition assay and albumin denaturation inhibition were performed, while in vivo measurements of carrageenan-induced paw oedema and formalin-induced pain in albino mice were performed. Acute toxicity and cytotoxicity studies of the fraction F2 were performed, as well as its HPLC, and some biochemical parameters were quantified. Uvaria comperei crude extract (UCCE) at 250 and 500 µg/mL completely inhibited albumin denaturation, while decreasing 75.5% of heat blood cell lysis at 500 µg/mL. The fractions 128-136 (F3), 10-11 (F1), and 56-62 (F2) at 500 µg/mL displayed a significant anti-inflammatory activity with percentages of inhibition of 60.5, 67.4, and 100%, respectively. Administration of fraction F2 (25, 50, and 100 mg/kg, p.o.) produced a dose-dependent inhibition of formalin-induced pain of 60.2% at 50 mg/kg in the neurogenic phase (p < 0.05) and 70.2% at 25 mg/kg in the inflammatory phase (p < 0.05). Similarly, the time-dependent increase in carrageenan-induced paw circumference induced by carrageenan was inhibited by pretreatment with F2: 50% of inhibition at 25 mg/kg after 30 min (p < 0.05) and 96.5% inhibition at 25 mg/kg after 6 h (p < 0.05). In this research, the fraction F2 presented its maximum analgesic property at 50 mg/kg, while it presented the highest anti-inflammatory property at 25 mg/kg. The oral lethal median dose (LD50) of F2 was determined to be greater than 2000 mg/kg; further low cytotoxicity in RAW cells was also observed. Overall, this work shows that the methanolic crude extract and fractions, mainly F2, of Uvaria comperei stem have interesting anti-inflammatory properties.

Molecular Docking and Study of the Anti-inflammatory Effect of Triterpene and Diarylheptanoid Isolated from Pellacalyx axillaris.

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of drugs widely used around the world for their analgesic, antipyretic and anti-inflammatory effect, but still have many limitations due to their side effects. So, these lead to the development of a new approach to search for a new product from natural plants that have similar therapeutic effects without common side effects like gastrointestinal ulcers. METHODS: The anti-inflammatory effect of ß-amyrin palmitate (1) as triterpene and 1,7-bis (4- hydroxyphenyl) hept-4-en-3-one (2) as diarylheptanoid, isolated from Pellacalyx axillaris was studied by molecular docking to find the probability of binding position and binding strength of new compounds with particular Prostaglandin G/H synthase 2 (PDB ID: 1CX2). In vivo acute anti-inflammatory activity of the isolated compounds (1 and 2) was evaluated in rats using the egg-white induced edema model of inflammation in a dose correspondent to 3 mg/Kg of Diclofenac Sodium. RESULTS: The tested isolated compounds showed a high activity to inhibit the swelling in paw edema and their anti-inflammatory effect began shortly after the injection of the egg white and continued to the end of the experiment in comparison to the reference and control. CONCLUSION: The isolated compounds show a rapid onset of action and a very potent effect, this may be related to their suitable acidity and may have perfect hydrophilic -lipophilic balance. This is the first study of anti-inflammatory effect using Paw edema model and molecular docking.

Dereplication of Siparuna brasiliensis extract with in vivo anti-inflammatory activity.

Siparuna brasiliensis is a medicinal plant widely used by indigenous communities of the Amazon rainforest to treat inflammatory diseases and related pathologies. Considering its ethnopharmacological application, it constitutes an important source of biologically active molecules in the development of anti-inflammatory drugs. This study describes a dereplication methodology of the bioactive extract from S. brasiliensis leaves and the evaluation of the anti-inflammatory potential in an in vivo inflammatory model with mice of the BALB/c lineage and in vitro using cell lines, as well as determining the production of an inflammatory mediator. From their charge-to-mass ratios (m/z) and elemental composition obtained through Ultrahigh-resolution mass spectrometry analysis by ESI(-)-Orbitrap MS and chromatographic profile by RP-HPLC-PDA, it was possible to annotate polyphenols with anti-inflammatory properties classified as flavonoids and organic acids. The administration of the extract significantly inhibited carrageenan-induced paw edema and showed effects similar to those of drug dexamethasone without affecting cell viability.

Inter-Varietal Variation in Phenolic Profile, Antioxidant, Anti-Inflammatory and Analgesic Activities of Two Brassica rapa Varieties: Influence on Pro-Inflammatory Mediators.

The present research study aims to appraise the potential of polyphenol-rich extracts from two Brassica rapa varieties on antioxidant, anti-inflammatory and analgesic activities using carrageenan-induced paw edema model in rats. Methanol extracts of peels and pulps of Brassica rapa yellow root (BRYR) and Brassica rapa white root (BRWR) were prepared using the soxhlet extraction technique. All four extracts were analyzed by reversed-phase high-pressure liquid chromatography (RP-HPLC) for the polyphenols, and results showed that 10 phenolic acids and 4 flavonoids were detected. Gallic acid was the major phenolic acid (174.6-642.3 mg/100 g of dry plant material) while catechin was the major (34.45-358.5 mg/100 g of dry plant material) flavonoid detected in the extracts. The total phenolic contents (TPC) of BRYR peel, BRWR peel, BRYR pulp and BRWR pulp extracts were in the range of 1.21-5.01 mg/g of dry plant material, measured as GAE, whereas the total flavonoid contents (TFC) were found in the range of 0.90-3.95 mg/g of dry plant material, measured as QE. BRYR peel extract exhibited the best DPPH radical scavenging activity (IC50, 3.85 µg/mL) and reducing potential as compared with other extracts. The in vivo anti-inflammatory potential was assessed by carrageenan-induced rat paw edema, and the analgesic potential was investigated by a hot plate test. Suppression of biochemical inflammatory biomarkers including C-reactive protein (CRP), rheumatoid factor (RF) and tumor necrosis factor (TNF-α), and interleukin-6 (IL-6) concentration were also determined. Results showed that BRYR peel extracts reduced paw edema and suppressed the production of TNF-α, IL-6, CRP and RF most significantly, followed by BRWR peel, BRYR pulp and BRWR pulp extracts. In addition, histopathology observation also supports the anti-inflammatory effect of peel extracts as being greater than that of root pulp extracts. Moreover, it was observed that the analgesic effect of the root-peel extracts was also more pronounced as compared with root-pulp extracts. It can be concluded that BRYR peel extract has higher phenolic contents and showed higher suppression of TNF-α, IL-6, CRP and RF, with strong antioxidant, anti-inflammatory and analgesic effects.

Antiulcerogenic Potential of the Ethanolic Extract of Ceiba speciosa (A. St.-Hil.) Ravenna Evaluated by In Vitro and In Vivo Studies.

Gastrointestinal diseases, such as peptic ulcers, are caused by a damage in the gastric mucosa provoked by several factors. This stomach injury is regulated by many inflammatory mediators and is commonly treated with proton-pump inhibitors, histamine H2 receptor blockers and antacids. However, various medicinal plants have demonstrated positive effects on gastric ulcer treatment, including plants of the Ceiba genus. The aim of this study was to evaluate the antiulcer and anti-inflammatory activities of the stem bark ethanolic extract of Ceiba speciosa (A. St.-Hil.) Ravenna. We performed a preliminary quantification of phenolic compounds by high-performance liquid chromatography-diode array detection (HPLC-DAD), followed by the prospection of other chemical groups through nuclear magnetic resonance (NMR) spectroscopy. A set of in vitro assays was used to evaluate the extract potential regarding its antioxidant activity (DPPH: 19.83 ± 0.34 µg/mL; TPC: 307.20 ± 6.20 mg GAE/g of extract), effects on cell viability and on the release of TNF-α in whole human blood. Additionally, in vivo assays were performed to evaluate the leukocyte accumulation and total protein quantification in carrageenan-induced air pouch, as well as the antiulcerogenic effect of the extract on an ethanol-induced ulcer in rats. The extract contains flavonoids and phenolic compounds, as well as sugars and quinic acid derivatives exhibiting potent antioxidant activity and low toxicity. The extract reduced the release of TNF-α in human blood and inhibited the activity of p38α (1.66 µg/mL), JAK3 (5.25 µg/mL), and JNK3 (8.34 µg/mL). Moreover, it reduced the leukocyte recruitment on the pouch exudate and the formation of edema, reverting the effects caused by carrageenan. The extract presented a significant prevention of ulcer formation and a higher reduction than the reference drug, Omeprazole. Therefore, C. speciosa extract has demonstrated relevant therapeutic potential for the treatment of gastric diseases, deserving the continuation of further studies to unveil the mechanisms of action of plant bioactive ingredients.

Acute Toxicity and Anti-Inflammatory Activity of Trattinnickia rhoifolia Willd (Sucuruba) Using the Zebrafish Model.

The species Trattinnickia rhoifolia Willd, (T. rhoifolia), which belongs to the Burseraceae family, is widely used in ethnopharmacological cultural practices by traditional Amazonian people for anti-inflammatory purposes, sometimes as their only therapeutic resource. Although it is used in teas, infusions, macerations and in food, the species is still unexplored in regard to its pharmacophoric potential and chemical profile. Therefore, the aim of this study was to conduct a phytochemical characterization of the hydroethanolic extract of T. rhoifolia leaves (HELTr) and to evaluate the acute toxicity and anti-inflammatory activity of this species using zebrafish (Danio rerio). The extract was analyzed by gas chromatography−mass spectrometry (GC-MS). The evaluation of the acute toxicity of the HELTr in adult zebrafish was determined using the limit test (2000 mg/kg), with behavioral and histopathological evaluations, in addition to the analysis of the anti-inflammatory potential of HELTr in carrageenan-induced abdominal edema, followed by the use of the computational method of molecular docking. The phytochemical profile of the species is chemically diverse, suggesting the presence of the fatty acids, ester, alcohol and benzoic acid classes, including propanoic acid, ethyl ester and hexadecanoic acid. In the studies of zebrafish performed according to the index of histopathological changes (IHC), the HELTr did not demonstrate toxicity in the behavioral and histopathological assessments, since the vital organs remained unchanged. Carrageenan-induced abdominal edema was significantly reduced at all HELTr doses (100, 200 and 500 mg/kg) in relation to the negative control, dimethyl sulfoxide (DMSO), while the 200 mg/kg dose showed significant anti-inflammatory activity in relation to the positive control (indomethacin). With these activities being confirmed by molecular docking studies, they showed a good profile for the inhibition of the enzyme Cyclooxygenase-2 (COX-2), as the interactions established at the sites of the receptors used in the docking study were similar to the controls (RCX, IMN and CEL). Therefore, the HELTr has an acceptable degree of safety for acute toxicity, defined in the analysis of behavioral changes, mortality and histopathology, with a significant anti-inflammatory action in zebrafish at all doses, which demonstrates the high pharmacophoric potential of the species. These results may direct future applications and drug development but still require further elucidation.

Fatty-Acid-Rich Agave angustifolia Fraction Shows Antiarthritic and Immunomodulatory Effect.

Agave angustifolia is a xerophytic species widely used in Mexico as an ingredient in sweet food and fermented beverages; it is also used in traditional medicine to treat wound pain and rheumatic damage, and as a remedy for psoriasis. Among the various A. angustifolia extracts and extract fractions that have been evaluated for their anti-inflammatory effects, the acetonic extract (AaAc) and its acetonic (F-Ac) and methanolic (F-MeOH) fractions were the most active in a xylene-induced ear edema model in mice, when orally administered. Four fractions resulting from chemically resolving F-Ac (F1-F4) were locally applied to mice with phorbol 12-myristate 13-acetate (TPA)-induced ear inflammation; F1 inhibited inflammation by 70% and was further evaluated in a carrageenan-induced mono-arthritis model. When administered at doses of 12.5, 25, and 50 mg/kg, F1 reduced articular edema and the spleen index. In addition, it modulated spleen and joint cytokine levels and decreased pain. According to a GC-MS analysis, the main components of F1 are fatty-acid derivatives: palmitic acid methyl ester, palmitic acid ethyl ester, octadecenoic acid methyl ester, linoleic acid ethyl ester, and oleic acid ethyl ester.

Phillygenin from Forsythia suspensa leaves exhibits analgesic potential and anti-inflammatory activity in carrageenan-induced paw edema in mice.

Forsythia suspensa (Thunb.) Vahl (Oleaceae) leaves are valuable sources of phillygenin. This study aimed to isolate phillygenin from F. suspensa leaves and examine its analgesic and anti-inflammatory effects. Phillygenin was successfully extracted and isolated from F. suspensa leaves after fermentation. Phillygenin significantly reduced the number of writhing induced by acetic acid, prolonged the latency period in the hot plate test, and inhibited the xylene-induced ear edema and carrageenan-induced paw edema in mice. IL-6, TNF-α, IL-1ß, NO, and PGE2 levels in the carrageenan-induced paw edema were notably reduced after pretreatment with phillygenin. Phillygenin significantly decreased the iNOS and COX-2 protein expressions and the IκB-α and NF-κB p65 phosphorylation. This study demonstrated that phillygenin is a potential therapeutic candidate for managing pain and inflammation-mediated disorders. The study contributes to the comprehensive development and utilization of F. suspensa leaves for economic and health care. PRACTICAL APPLICATIONS: Phillygenin is one of the major active ingredients in Forsythia suspensa. But the content of phillygenin in F. suspensa is very low which limits its application. Phillygenin has potential pharmacological activity and anti-inflammatory properties. However, the potential effects of phillygenin on analgesic activity have not been clarified. Furthermore, the data on its anti-inflammatory activity in vivo are relatively limited. This study evaluated the analgesic activity for the first time and the acute anti-inflammatory effect of phillygenin from F. suspensa leaves by fermentation, which indicated phillygenin is a potential therapeutic candidate for managing pain and inflammation-mediated disorders.

Anti-inflammatory potential of berberine-rich extract via modulation of inflammation biomarkers.

Berberine-rich extract (BRE) prepared from Berberis lycium root bark using green extraction approach and its marker compound berberine has a broad spectrum of clinical applications. Berberine's potential pharmacological effects include anticancer, antidiarrheal, antidiabetic, antimicrobial and anti-inflammatory activities. In current work, BRE and berberine were evaluated for their therapeutic prospects in inflammation models. The comparative effect of BRE and berberine against inflammation was determined through in vitro chemiluminescence technique. The in vivo anti-inflammatory evaluation of BRE and berberine (25, 75, and 125 mg/kg) compared to diclofenac (10 mg/kg) was performed in carrageenan and formaldehyde-induced inflammation in Wistar rats. Histopathological and biochemical studies were conducted to find the comparative anti-inflammatory potential of BRE and berberine on pathological hallmarks induced by formaldehyde. Moreover, the modulatory effects on inflammatory biomarkers were also investigated through qPCR. ELISA (enzyme-linked immunoassay test assay) was performed to investigate the expression of pathological protein biomarkers like TNF-α and IL-6 and levels of antioxidant enzymes were estimated in liver homogenates. Both BRE and berberine markedly (p < .001) reduced paw diameter and inflammation in carrageenan and formaldehyde-induced inflammation. The levels of antioxidant enzymes were recovered (p < .001) by BRE and berberine treatments, and compared to the formaldehyde-treated inflammation model. Both BRE and berberine remarkably downregulated the mRNA and protein expression of inflammatory biomarkers. BRE similar to berberine mitigated the level of antioxidant enzymes in liver homogenate. The undertaken study suggests that BRE, a natural, green, and therapeutically bioequivalent to berberine could be used as an economical phytomedicine in the treatment of inflammatory disorders. PRACTICAL APPLICATIONS: Anti-inflammatory drugs like NSAIDS are associated with serious adverse effects like gastrointestinal ulcer, worsening of preexisting cardiovascular disorders, and renal failure. Therefore, there is a constant demand to develop novel, inexpensive therapeutic strategies to treat the inflammatory disorder with the least harmful effects. Pure phytochemicals with anti-inflammatory potential are costly and hard to isolate, therefore green microwave-assisted extraction technique is developed to get the rich bioequivalent extract. Berberis lycium a medicinal plant with berberine as a major bioactive constituent, has wide acceptance in traditionally used medicine and as food. Pharmacological studies revealed its hepatoprotective, anticancer, antidiabetic, and antihypertensive activities. BRE was prepared by green microwave-assisted extraction and enrichment by resin column to get a higher yield of berberine. The comparative anti-inflammatory effect of BRE and berberine was determined by in vitro and in vivo studies. Results obtained from this experimental work contribute beneficial guidance that reinforces the use of the BRE to treat inflammatory disorders.

Unani Formulation Habb-e-Suranjan: A Treasure of Biological Activities.

Habb-e-Suranjan (HES), an Unani formulation, has been studied for its anti-inflammatory properties in both in vitro and in vivo experiments. HES is recommended for arthritis, gout, and joint pain. The current endeavor is an attempt to put it to the test and verify its efficacy scientifically. It was tested for DPPH, hydroxyl, and nitric oxide scavenging activities. It was shown that HES had the greatest TAC and FRAC values when compared to catechin and ascorbic acid. HES exhibited DPPH and hydroxyl radical scavenging activity that was dose-dependent. Incubation of sodium nitroprusside solutions in PBS at 25°C for 150 min resulted in the production of nitric oxide. Nitric oxide production was effectively decreased by HES. Anti-inflammatory medications boosted the migration of PMN cells toward the chemoattractant FMLP in an agarose experiment of PMN chemotaxis. In carrageenan-induced rat paw edema, in the HES-treated group, paw thickness was 3.021 ± 0.084 at t = 0, but it showed an increase in paw inflammation after one hour, i.e., 3.195 ± 0.082 cm which again showed a decrease in paw thickness up to 4th hour, i.e., 3.018 ± 0.078, 2.98 ± 0.032, and 2.684 ± 0.061 at t = 2, 3, and 4, respectively. It showed again getting back to the normal thickness of paw at t = 24 hrs, i.e., 3.029 ± 0.118 cm. It is concluded that the formulation is potent enough and can be used effectively for the treatment of inflammation and associated health issues. Moreover, there is much scope to evaluate its effectiveness using different in vitro and in vivo models.