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.

Reduction of Edema and Pain in Transcutaneous Electrical Nerve Stimulation Treated-Arthritic Rat.

Transcutaneous electrical nerve stimulation (TENS) has been used to reduce pain or improve motor function in musculoskeletal and neurological disorders in the clinic. Although some studies have suggested electrotherapy as an intervention for edema, the effects and mechanisms of TENS on inflammation-induced edema remain unclear. Thus, we aimed to investigate the effects of TENS on arthritic pain with edema. 1% carrageenan was injected into the right tibiofemoral joint of 69 male Sprague-Dawley rats (200-250 g). After the development of arthritic pain, low-frequency (4-Hz, Low-TENS, n = 25) and high-frequency (100-Hz, High-TENS, n = 25) TENS with sub-motor threshold or placebo-TENS (n = 19) was applied for 20-min to medio-lateral part of the ipsilateral side. Weight bearing and knee-bend tests were used to assess pain-like behaviors. Also, we examined the size of edema and measured tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) levels in the synovium by western blot. Eight rats in each of the two TENS groups were injected with Naloxone. Edema was reduced in the low- and high-frequency TENS groups at 6-h. TENS-treated rats showed reduced pain in the knee-bend test at 6-h. We observed decreased weight load shifts on the ipsilateral side in TENS groups. Naloxone reduced these effects. TNF-α and IL-1ß expression decreased in the synovial membrane at 6-h. These results suggest that low- and high-frequency TENS have acutely positive effects on inflammatory edema, with the management of arthritic pain and reduction in pro-inflammatory mediators. Therefore, Low-TENS and High-TENS may be useful in treating acute inflammatory pain and edema.

Anti-inflammatory, analgesic, antitussive and antipyretic activities of polyphenol-enriched fraction from Nymphaea candida.

ETHNOPHARMACOLOGICAL RELEVANCE: "Snow-white waterlily" (Nymphaea candida) dried flower possesses various efficacy in Uighur medicine such as reducing fever and nourishing the liver, anti-inflammatory and cough relieving, moistening the throat and quenching thirst. AIM OF THE STUDY: Polyphenols are characteristic component of N. candida as well as its quality markers, and the purpose of this study was to conduct investigations into anti-inflammatory, antitussive, antipyretic, and analgesic activities of the polyphenol-enriched fraction from N. candida (NCTP) in order to validate the traditional efficacy of this plant. MATERIALS AND METHODS: The polyphenols in NCTP were analyzed by HPLC, and an acute oral toxicity study was conducted for NCTP. The anti-inflammatory activities of NCTP were evaluated using xylene induced ear edema, capillary permeability, cotton pellet granuloma, and carrageenan-induced rat paw edema, of which multiple biochemical indices were measured in carrageenan-induced rat paw edema such as prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2),5-lipoxygenase (5-LOX), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) activities; the analgesic activities were investigated using acetic acid writhing, hot plate test, and formalin test; the anti-tussive and antipyretic effects were tested by ammonia induced cough in mice and yeast-induced fever respectively. RESULTS: NCTP with LD50 of 5222 mg/kg was low toxicity and safety. NCTP (200 mg/kg) could significantly reduce ear swelling and capillary permeability by 30.63% and 31.37%, respectively. NCTP revealed 15.76% inhibiting activities in cotton pellet granuloma in mice at a dosage of 200 mg/kg. Furthermore, NCTP (50, 100, and 200 mg/kg) substantially decreased carrageenin-induced paw edema in rats between 1 and 5 h, and NCTP could decrease PGE2, 5-LOX, COX-2 levels as well as IL-6, IL-1ß, TNF-α activities compared with the control group; NCTP could decrease MDA contents in carrageenin-induced rise, and increase SOD and GSH activities. Furthermore, the dose-dependent inhibition effect of NCTP on pain was revealed in the hot plate experiment. In addition to reducing the amount of writhes brought on by acetic acid, NCTP (50, 100, and 200 mg/kg) significantly inhibited pain latency against both stages of the formalin test. Moreover, NCTP (50, 100, 200 mg/kg) showed the better antitussive activities in mice in a dose-dependent manner. In the yeast-induced pyrexia test, dosages of 50, 100, and 200 mg/kg resulted in a statistically significant drop in rectal temperature. CONCLUSION: The experimental results proved the analgesic, anti-inflammatory, anti-tussive and antipyretic activities of the polyphenol-enriched fraction from N. candida, and supported the traditional use of this plant as well.

A new lymphedema treatment using pyro-drive jet injection.

Lymphedema, resulting from impaired lymphatic drainage, causes inflammation, fibrosis and tissue damage leading to symptoms such as limb swelling and restricted mobility. Despite various treatments under exploration, no standard effective therapy exists. Here a novel technique using the pyro-drive jet injection (PJI) was used to create artificial clefts between collagen fibers, which facilitated the removal of excess interstitial fluid. The PJI was used to deliver a mixture of lactated Ringer's solution and air into the tail of animals with secondary skin edema. Edema levels were assessed using micro-CT scanning. Histopathological changes and neovascularization were evaluated on the injury-induced regenerative tissue. Regarding tissue remodeling, we focused on connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF)-C. PJI markedly diminished soft tissue volume in the experimental lymphedema animals compared to the non-injected counterparts. The PJI groups exhibited a significantly reduced proportion of inflammatory granulation tissue and an enhanced density of lymphatic vessels and α-smooth muscle actin (αSMA)-positive small vessels in the fibrous granulation tissue compared to the controls. In addition, PJI curtailed the prevalence of CTGF- and VEGF-C-positive cells in regenerative tissue. In a lymphedema animal model, PJI notably ameliorated interstitial edema, promoted lymphatic vessel growth, and bolstered αSMA-positive capillaries in fibrous granulation tissue. PJI's minimal tissue impact post-lymph node dissection indicates significant potential as an early, standard preventative measure. Easily applied in general clinics without requiring specialized training, it offers a cost-effective and highly versatile solution to the management of lymphedema.

Anti-inflammatory potential of a Thai traditional remedy called Prabchompoothaweep in an animal model of acute and sub-acute inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Prabchompoothaweep (PCT) is a Thai remedy which is composed of 23 herbs and has been added onto the National List of Essential Medicines (NLEM) of Thailand. This remedy has been used to treat allergic rhinitis and asthma in Thai traditional medicine for many years. Furthermore, a few studies have reported anti-allergic, anti-malarial, anti-inflammatory and antioxidant activities. AIM OF THE STUDY: This study aims to evaluate anti-inflammatory activity of PCT extract in an animal model. MATERIALS AND METHODS: The animal model of acute inflammation was studied over a 24-h period, utilizing the method of carrageenan-induced paw oedema. In addition, sub-acute inflammation was examined over 7 days, using the formalin-induced paw oedema method. The treatment groups received PCT extracts, via the oral route, at 1-h prior to injection and then the sub plantar of the rat right paw was injected with the named substances to generate paw oedema. The paw thickness was measured by vernier caliper at regular intervals after injection. At the end of experiment, the blood and paw tissues were collected for measurement of pro-inflammatory cytokines and histological examination respectively. RESULTS: In acute inflammation, all doses of PCT extract (250, 500 and 1000 mg/kg p.o.) significantly reduced paw thickness after the first 3 h in a dose-dependent manner and the percentage of inhibition was 38.7%, 47.8% and 49.5% respectively. The pro-inflammatory cytokines, including TNF-α and IL-1ß, statistically decreased with all doses of the extracts. However, the histological examination did not reveal significant results due to the short time duration. As regards to sub-acute inflammation, all doses of PCT extract significantly reduced paw thickness with 12.78%, 23.64% and 35.78%, in a dose dependent manner. Also, the pro-inflammatory cytokines (TNF-α and IL-1ß) significantly decreased at day 7. Interestingly, the histological examination of paw tissue demonstrated reductions of mononuclear infiltrations of inflammatory cells, this was observed in the group receiving PCT extracts, also in a dose-dependent manner. CONCLUSION: Therefore, PCT exerted anti-inflammatory activity in an animal model of acute and sub-acute inflammation, suggesting that it could be used as a new source for treatment of inflammatory diseases.

Ameliorating effect of polyherbal formulation (Febrojith) on acute and chronic inflammatory model via inhibiting inflammation and oxidative stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammation is a complex biological response of the tissue to noxious stimuli, which causes several debilitating inflammatory disorders. Currently, various conventional medicines are available, but their consumption causes adverse effects, hence researchers focused on alternatives like medical herbs from natural sources, as one of the most promising sources of therapeutic agents for inflammation. Febrojith is a well-known traditional Ayurvedic formulation obtained from the treasures of Ayurveda with a unique blend of herbs that are used effectively in preventing and combating a broad spectrum of infections, fevers, and also enhancing immunity for many years. However, its anti-inflammatory, efficacy and underlying mechanism remained unexplored. AIM OF THE STUDY: In the present study, we investigated the chemical characterization and in vivo anti-inflammatory efficacy of Febrojith (FB) on acute and chronic inflammatory models via inhibiting inflammation and oxidative stress. MATERIALS AND METHODS: FB was analyzed for chemical characterization & its phytoconstituents by UV-Vis spectrum, FT-IR, and GC-MS analysis. The anti-inflammatory activity of FB was studied on carrageenan-induced acute and adjuvant-induced chronic experimental models. The inflammatory cytokines and mediators were measured using the ELISA & Colorimetry techniques. Histopathology and cytology of paw tissue and synovium were analyzed by H&E and Papanicolau's (PAP)-staining methods. RESULTS: 100 mg/kg bwt was found to be a potent dose from the carrageenan model and evaluated its effect in the adjuvant-induced chronic arthritic model. In the chronic model, 84% of edema inhibition was observed at the dose of 100 mg/kg bwt. Moreover, the supplementation of FB was shown to significantly (p ≤ 0.05) decrease the TBARS level and activity of myeloperoxidase in the paw tissue. In addition, adjuvant-induced production of various pro-inflammatory cytokines like TNF-α, IL-1ß, IL-6, PGE2, NO and COX-2 were suppressed in inflamed rats subjected to FB supplementation. It also revealed that FB supplementation significantly (p ≤ 0.05) reduced the haematological markers. From the histopathology and cytological analysis, we found a reduction in the edema formation, and infiltration of inflammatory cells after the supplementation of FB. CONCLUSION: In conclusion, FB might be used as an effective and potent drug against inflammation.

Impact of Eucalyptus maculata Hook resin exudate constituents on reducing COX-2 gene expression: In-vivo anti-inflammatory, molecular docking and dynamics studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Eucalyptus maculata Hook from the Myrtaceae family is a native Australian plant that is frequently cultivated in Egypt. Many Eucalyptus species, including E. maculata, were widely used by the Dharawal, the indigenous Australian people, for their anti-inflammatory properties. AIM OF THE STUDY: The purpose of this study was to determine the anti-inflammatory activity of the ethanol extract of E. maculata resin exudate, its methylene chloride and n-butanol fractions, as well as the isolated compounds. MATERIALS AND METHODS: the ethanol extract was partitioned by methylene chloride, and n-butanol saturated with water. The fractions were chromatographed to isolate pure compounds. In-vivo anti-inflammatory activity of the ethanol extract, the fractions at a dose of 200 mg/kg, and the isolated compounds (20 mg/kg) was estimated using carrageenan-induced rat paws edema method against indomethacin (20 mg/kg). The activity was supported by histopathological and biochemical parameters. RESULTS: Three isolated compounds were identified as aromadendrin (C1), 7-O-methyl aromadendrin (C2), and naringenin (C3). Our findings demonstrated that the tested fractions significantly reduced the paw edema starting from the 3rd to the 5th hour as compared to the positive control, compounds C2 and C3 showed the greatest significant reduction in paw edema. The ethanol extract, fractions, C2, and C3 demonstrated an anti-inflammatory potential through reducing the levels of TNF-α, IL-6, and PGE2, as well as COX-2 protein expression compared to the negative control. These results were supported by molecular docking, which revealed that the isolated compounds had high affinity to target COX-1 and COX-2 active sites with docking scores ranging from -7.3 to -9.6 kcal mol-1 when compared to ibubrofen (-7.8 and -7.4 kcal mol-1, respectively). Molecular dynamics simulations were also performed and confirmed the docking results. CONCLUSION: The results supported the traditional anti-inflammatory potency of E. maculata Hook, and the biochemical mechanisms underlying this activity were highlighted, opening up new paths for the development of potent herbal anti-inflammatory medicine. Finally, our findings revealed that E. maculata resin constituents could be considered as promising anti-inflammatory drug candidates.

Clinical and histological features and treatment outcomes of patients with Morbihan disease: a systematic review.

Morbihan disease (MD) is considered a rare complication of rosacea, which is difficult to diagnose and challenging to treat. Here, we performed a systematic review of available case reports and case series to summarize key clinical and pathologic features of and successful treatment regimens for MD. We conducted a search of the PubMed/MEDLINE, EMBASE, and Cochrane electronic databases from their inception to the date of search on March 6, 2023. We found that MD affects patients in the fifth decade of life on average, more commonly reported in male than female (69% vs 31%). Clinically, MD affects the eyelids, cheeks, and forehead most commonly, presenting as non-pitting, erythematous edema or an edematous plaque. On biopsy, the pathologic features, such as dermal edema, sebaceous hyperplasia, perivascular and periadnexal inflammatory infiltrate, and granulomatous reaction, are frequently reported. Out of 55 patients who were able to achieve complete response without recurrence, 35% of patients were treated with isotretinoin and 22% were treated with tetracycline antibiotics with a daily dosage range of 20-80 mg and 40-200 mg, respectively. Out of those 55 patients, 22% and 7% were treated successfully with surgical intervention and intralesional injection of steroids, respectively. Additionally, lymphatic drainage has been shown to be an effective adjunctive therapeutic tool. More studies are necessary to understand the disease mechanism to improve the diagnosis of and develop evidence-based therapies for MD.

Exploring the anti-inflammatory potential of Colocasia esculenta root extract in in-vitro and in-vivo models of inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Colocasia esculenta (CE) (L.) Schott is an annual herbaceous tropical plant from the family of Araceae which has been traditionally used for the healing of various ailments such as asthma, arthritis, internal hemorrhage, diarrhea, and neurological disorders. The plant is reported to have potential anti-microbial, anti-fungal, antimetastatic, anti-hepatotoxic, and anti-lipid peroxidative activities. AIM OF THE STUDY: The present study is designed to explore the potential anti-inflammatory property of Colocasia esculenta methanolic root extract (CEMRE) on carrageenan-induced rat paw edema and lipopolysaccharide (LPS) stimulated RAW264.7 cells. MATERIALS AND METHODS: Carrageenan-induced rat paw edema model was used to investigate the in vivo anti-inflammatory action of CEMRE. Adult male Wistar rats (180-220 g; n = 6) were pre-treated with CEMRE (100, 200, and 400 mg/kg BW) orally before 1 h of injection of 1% carrageenan. Indomethacin (10 mg/kg BW) was given orally as the standard drug. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), nitric oxide (NO), prostaglandinE2 (PGE2), and cytokines levels were measured. Liquid chromatography-mass spectrometry (LC-MS) was done to identify the phytoconstituents present in CEMRE. The inhibitory activity of CEMRE was investigated against cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in in vitro assessment of LPS-stimulated RAW264.7 cells. The RAW 264.7 cells were pre-treated with Indomethacin (5 µM and 10 µM) and CEMRE (17 µg/ml and 34 µg/ml) followed by induction of LPS (1 µg/ml) for 24 h. Docking analyses were also performed to explore the interaction of important phytoconstituents (Sinapic acid, Acetylsalicylic acid, L-fucose, Salicylic acid, Quinic acid, Zingerone, and Gingerol) of CEMRE with COX-2 and iNOS. RESULTS: Pre-treatment with CEMRE (400 mg/kg) could inhibit the paw inflammation significantly which was elevated due to carrageenan induction. The inhibition is comparable to that of the standard drug Indomethacin. The concentration of serum AST, ALT, ALP, NO, PGE2 and cytokines were also considerably lowered in the CEMRE-treated group as compared to the carrageenan-induced group. CEMRE (34 µg/ml) inhibited the LPS-stimulated relative expression of mRNA of COX-2 and iNOS and significantly reduced the expression of nitric oxide and prostaglandin E2. Docking analyses revealed promising interaction with low binding energies between Sinapic acid with both the target proteins COX-2 and iNOS. CONCLUSION: Collectively, our results suggested that CEMRE exhibited effective anti-inflammatory actions on carrageenan-induced rat paw edema and LPS-treated RAW 264.7 cells by reducing the in vivo paw edema inhibition, inhibiting the serum NO, PGE2, cytokines and also reduced the in vitro production of NO, PGE2 along with expressions of mRNA COX-2 and iNOS. Molecular docking demonstrated good binding affinities among the target proteins and ligand Sinapic acid. Thus the bioactive compound from CE need to be isolated and purified.

Analgesic and anti-inflammatory potential of ethanolic extract from Serjania erecta leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: The infusion of Serjania erecta Radlk (Sapindaceae) (popular name "cipó-cinco-folhas") leaves is used in popular medicine to treat back pain. The anti-inflammatory, anti-hyperalgesic and anti-nociceptive properties of the ethanolic extract from S. erecta leaves (EESE) has not been yet completely clarified. AIM OF THE STUDY: The present study investigated the anti-hyperalgesic, anti-nociceptive and anti-inflammatory properties of EESE in experimental models in mice. MATERIAL AND METHODS: EESE was fractionated by chromatographic techniques and the compound was identified by nuclear magnetic resonance (NMR), infrared (IR) spectrum, ultraviolet (UV) methods. Mice received a single dose of EESE by oral route (30, 100, and 300 mg/kg, p.o.) and were submitted to nociception induced by formalin, pleurisy induced by carrageenan and peritonitis induced by zymosan models. Mice also received EESE (30 and 100 mg/kg, p.o.) for 22 days in Complete Freund Adjuvant (CFA) model and another group received EESE for 7 days (30 and 100 mg/kg, p.o.) in pleurisy induced by Bacillus Calmette-Guerin (BCG). The cytotoxicity (MTT), phagocytic and chemotactic inhibitory activities of EESE were performed in in vitro assays. RESULTS: The fractionation of EESE led to the identification of kaempferol-3-O-α-L-rhamnopyranoside. The oral administration of all doses of EESE decreased the nociceptive response induced by formalin. EESE significantly inhibited leukocyte migration in carrageenan-induced pleurisy and zymosan peritonitis models. The daily administration of EESE during for 7 days inhibited the leukocyte migration and the mycobacteria growth of pleural material obtained from animals which received BCG. EESE significantly reduced edema, cold allodynia and mechanical hyperalgesia responses induced by CFA. EESE did not induce cytotoxicity, and also decreased the leukocyte phagocytic activity, as well as, neutrophil chemotaxis. CONCLUSIONS: EESE showed analgesic and anti-inflammatory properties in acute and persistent experimental models in mice. EESE also reduced in vitro leukocyte chemotaxis and phagocytic activity without inducing cytotoxicity. The continuous oral treatment with EESE was effective against hyperalgesia and inflammation and these results could explain the popular use of S. erecta as an analgesic natural agent.

MRI of Potassium and Sodium Enables Comprehensive Analysis of Ion Perturbations in Skeletal Muscle Tissue After Eccentric Exercise.

OBJECTIVES: The aims were to investigate if potassium ( 39 K) magnetic resonance imaging (MRI) can be used to analyze changes in the apparent tissue potassium concentration (aTPC) in calf muscle tissue after eccentric exercise and in delayed-onset muscle soreness, and to compare these to corresponding changes in the apparent tissue sodium concentration (aTSC) measured with sodium ( 23 Na) MRI. MATERIALS AND METHODS: Fourteen healthy subjects (7 female, 7 male; 25.0 ± 2.8 years) underwent 39 K and 23 Na MRI at a 7 T MR system, as well as 1 H MRI at a 3 T MR system. Magnetic resonance imaging data and blood samples were collected at baseline (t0), directly after performing eccentric exercise (t1) and 48 hours after exercise (t2). Self-reported muscle soreness was evaluated using a 10-cm visual analog scale for pain (0, no pain; 10, worst pain) at t0, t1, and t2. Quantification of aTPC/aTSC was performed after correcting the measured 39 K/ 23 Na signal intensities for partial volume and relaxation effects using 5 external reference phantoms. Edema volume and 1 H T 2 relaxation times were determined based on the 1 H MRI data. Participants were divided according to their increase in creatine kinase (CK) level into high (CK t2 ≥ 10·CK t0 ) and low CK (CK t2 < 10·CK t0 ) subjects. RESULTS: Blood serum CK and edema volume were significantly increased 48 hours after exercise compared with baseline ( P < 0.001). Six participants showed a high increase in blood serum CK level at t2 relative to baseline, whereas 8 participants had only a low to moderate increase in blood serum CK. All participants reported increased muscle soreness both at rest and when climbing stairs at t1 (0.4 ± 0.7; 1.4 ± 1.2) and t2 (1.6 ± 1.4; 4.8 ± 1.9) compared with baseline (0 ± 0; 0 ± 0). Moreover, aTSC was increased at t1 in exercised muscles of all participants (increase by 57% ± 24% in high CK, 73% ± 33% in low CK subjects). Forty-eight hours after training, subjects with high increase in blood serum CK still showed highly increased aTSC (increase by 79% ± 57% compared with t0). In contrast, aTPC at t2 was elevated in exercised muscles of low CK subjects (increase by 19% ± 11% compared with t0), in which aTSC had returned to baseline or below. Overall, aTSC and aTPC showed inverse evolution, with changes in aTSC being approximately twice as high as in aTPC. CONCLUSIONS: Our results showed that 39 K MRI is able to detect changes in muscular potassium concentrations caused by eccentric exercise. In combination with 23 Na MRI, this enables a more holistic analysis of tissue ion concentration changes.

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.

Elucidation of the Metabolite Profile of Yucca gigantea and Assessment of Its Cytotoxic, Antimicrobial, and Anti-Inflammatory Activities.

The acute inflammation process is explained by numerous hypotheses, including oxidative stress, enzyme stimulation, and the generation of pro-inflammatory cytokines. The anti-inflammatory activity of Yucca gigantea methanol extract (YGME) against carrageenan-induced acute inflammation and possible underlying mechanisms was investigated. The phytochemical profile, cytotoxic, and antimicrobial activities were also explored. LC-MS/MS was utilized to investigate the chemical composition of YGME, and 29 compounds were tentatively identified. In addition, the isolation of luteolin-7-O-ß-d-glucoside, apigenin-7-O-ß-d-glucoside, and kaempferol-3-O-α-l-rhamnoside was performed for the first time from the studied plant. Inflammation was induced by subcutaneous injection of 100 µL of 1% carrageenan sodium. Rats were treated orally with YGME 100, 200 mg/kg, celecoxib (50 mg/kg), and saline, respectively, one hour before carrageenan injection. The average volume of paws edema and weight were measured at several time intervals. Levels of NO, GSH, TNF-α, PGE-2, serum IL-1ß, IL-6 were measured. In additionally, COX-2 immunostaining and histopathological examination of paw tissue were performed. YGME displayed a potent anti-inflammatory influence by reducing paws edema, PGE-2, TNF-α, NO production, serum IL-6, IL-1ß, and COX-2 immunostaining. Furthermore, it replenished the diminished paw GSH contents and improved the histopathological findings. The best cytotoxic effect of YGME was against human melanoma cell line (A365) and osteosarcoma cell line (MG-63). Moreover, the antimicrobial potential of the extract was evaluated against bacterial and fungal isolates. It showed potent activity against Gram-negative, Gram-positive, and fungal Candida albicans isolates. The promoting multiple effects of YGME could be beneficial in the treatment of different ailments based on its anti-inflammatory, antimicrobial, and cytotoxic effects.

Oral and Topical Anti-Inflammatory and Antipyretic Potentialities of Araucaria bidiwillii Shoot Essential Oil and Its Nanoemulsion in Relation to Chemical Composition.

Different parts of Araucaria bidiwillii (bunya pin) trees, such as nuts, seeds, bark, and shoots, are widely used in cooking, tea, and traditional medicines around the world. The shoots essential oil (EO) has not yet been studied. Herein, the chemical profile of A. bidiwillii shoots EO (ABSEO) was created by GC-MS analysis. Additionally, the in vivo oral and topical anti-inflammatory effect against carrageenan-induced models, as well as antipyretic potentiality of ABSEO and its nanoemulsion were evaluated. Forty-three terpenoid components were identified and categorized as mono- (42.94%), sesqui- (31.66%), and diterpenes (23.74%). The main compounds of the ABSEO were beyerene (20.81%), α-pinene (16.21%), D-limonene (14.22%), germacrene D (6.69%), ß-humulene (4.14%), and sabinene (4.12%). The ABSEO and its nanoemulsion exhibited significant inflammation suppression in carrageenan-induced rat paw edema model, in both oral (50 and 100 mg/kg) and topical (5% in soyabean oil) routes, compared to the control and reference drugs groups. All the results demonstrated the significant inflammation reduction via the inflammatory cytokines (IL-1ß and IL8), nitrosative (NO), and prostaglandin E2 (PGE2) supported by the histopathological studies and immunohistochemical assessment of MMP-9 and NF-κß levels in paw tissues. Moreover, the oral administration of ABSEO and its nanoemulsion (50 and 100 mg/kg) exhibited antipyretic activity in rats, demonstrated by the inhibition of hyperthermia induced by intramuscular injection of brewer's yeast. These findings advised that the use of ABSEO and its nanoemulsion against numerous inflammatory and hyperthermia ailments that could be attributed to its active constituents.

Phytochemical Profile, Free Radical Scavenging and Anti-Inflammatory Properties of Acalypha Indica Root Extract: Evidence from In Vitro and In Vivo Studies.

In our in vitro and in vivo studies, we used Acalypha indica root methanolic extract (AIRME), and investigated their free radical scavenging/antioxidant and anti-inflammatory properties. Primarily, phytochemical analysis showed rich content of phenols (70.92 mg of gallic acid/g) and flavonoids (16.01 mg of rutin/g) in AIRME. We then performed HR-LC-MS and GC-MS analyses, and identified 101 and 14 phytochemical compounds, respectively. Among them, ramipril glucuronide (1.563%), antimycin A (1.324%), swietenine (1.134%), quinone (1.152%), oxprenolol (1.118%), choline (0.847%), bumetanide (0.847%) and fenofibrate (0.711%) are the predominant phytomolecules. Evidence from in vitro studies revealed that AIRME scavenges DPPH and hydroxyl radicals in a concentration dependent manner (10-50 µg/mL). Similarly, hydrogen peroxide and lipid peroxidation were also remarkably inhibited by AIRME as concentration increases (20-100 µg/mL). In vitro antioxidant activity of AIRME was comparable to ascorbic acid treatment. For in vivo studies, carrageenan (1%, sub-plantar) was injected to rats to induce localized inflammation. Acute inflammation was represented by paw-edema, and significantly elevated (p < 0.05) WBC, platelets and C-reactive protein (CRP). However, AIRME pretreatment (150/300 mg/kg bodyweight) significantly (p < 0.05) decreased edema volume. This was accompanied by a significant (p < 0.05) reduction of WBC, platelets and CRP with both doses of AIRME. The decreased activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase in paw tissue were restored (p < 0.05 / p < 0.01) with AIRME in a dose-dependent manner. Furthermore, AIRME attenuated carrageenan-induced neutrophil infiltrations and vascular dilation in paw tissue. For the first time, our findings demonstrated the potent antioxidant and anti-inflammatory properties of AIRME, which could be considered to develop novel anti-inflammatory drugs.

Natural Coumarins: Exploring the Pharmacological Complexity and Underlying Molecular Mechanisms.

Coumarins belong to the benzopyrone family commonly found in many medicinal plants. Natural coumarins demonstrated a wide spectrum of pharmacological activities, including anti-inflammatory, anticoagulant, anticancer, antibacterial, antimalarial, casein kinase-2 (CK2) inhibitory, antifungal, antiviral, Alzheimer's disease inhibition, neuroprotective, anticonvulsant, phytoalexins, ulcerogenic, and antihypertensive. There are very few studies on the bioavailability of coumarins; therefore, further investigations are necessitated to study the bioavailability of different coumarins which already showed good biological activities in previous studies. On the evidence of varied pharmacological properties, the present work presents an overall review of the derivation, availability, and biological capacities of coumarins with further consideration of the essential mode of their therapeutic actions. In conclusion, a wide variety of coumarins are available, and their pharmacological activities are of current interest thanks to their synthetic accessibility and riches in medicinal plants. Coumarins perform the valuable function as therapeutic agents in a range of medical fields.

Low dose of quercetin-loaded pectin/casein microparticles reduces the oxidative stress in arthritic rats.

AIMS: Quercetin has been investigated as an agent to treat rheumatoid arthritis. At high doses it improves inflammation and the antioxidant status of arthritic rats, but it also exerts mitochondriotoxic and pro-oxidant activities. Beneficial effects of quercetin have not been found at low doses because of its chemical instability and low bioavailability. In the hope of overcoming these problems this study investigated the effects of long-term administration of quercetin-loaded pectin/casein microparticles on the oxidative status of liver and brain of rats with adjuvant-induced arthritis. MAIN METHODS: Particle morphology was viewed with transmission electron microscopy and the encapsulation efficiency was measured indirectly by X-ray diffraction. Quercetin microcapsules (10 mg/Kg) were orally administered to rats during 60 days. Inflammation indicators and oxidative stress markers were measured in addition to the respiratory activity and ROS production in isolated mitochondria. KEY FINDINGS: Quercetin was efficiently encapsulated inside the polymeric matrix, forming a solid amorphous solution. The administration of quercetin microparticles to arthritic rats almost normalized protein carbonylation, lipid peroxidation, the levels of reactive oxygen species as well as the reduced glutathione content in both liver and brain. The paw edema in arthritic rats was not responsive, but the plasmatic activity of ALT and the mitochondrial respiration were not affected by quercetin, indicating absence of mitochondriotoxic or hepatotoxic actions. SIGNIFICANCE: Quercetin-loaded pectin/casein microcapsules orally administered at a low dose improve oxidative stress of arthritic rats without a strong anti-inflammatory activity. This supports the long-term use of quercetin as an antioxidant agent to treat rheumatoid arthritis.

Anti-Inflammatory, Antipyretic, and Analgesic Properties of Potamogeton perfoliatus Extract: In Vitro and In Vivo Study.

Natural antioxidants, especially those of plant origins, have shown a plethora of biological activities with substantial economic value, as they can be extracted from agro-wastes and/or under exploited plant species. The perennial hydrophyte, Potamogeton perfoliatus, has been used traditionally to treat several health disorders; however, little is known about its biological and its medicinal effects. Here, we used an integrated in vitro and in vivo framework to examine the potential effect of P. perfoliatus on oxidative stress, nociception, inflammatory models, and brewer's yeast-induced pyrexia in mice. Our results suggested a consistent in vitro inhibition of three enzymes, namely 5-lipoxygenase, cyclooxygenases 1 and 2 (COX-1 and COX-2), as well as a potent antioxidant effect. These results were confirmed in vivo where the studied extract attenuated carrageenan-induced paw edema, carrageenan-induced leukocyte migration into the peritoneal cavity by 25, 44 and 64% at 200, 400 and 600 mg/kg, p.o., respectively. Moreover, the extract decreased acetic acid-induced vascular permeability by 45% at 600 mg/kg, p.o., and chemical hyperalgesia in mice by 86% by 400 mg/kg, p.o., in acetic acid-induced writhing assay. The extract (400 mg/kg) showed a longer response latency at the 3 h time point (2.5 fold of the control) similar to the nalbuphine, the standard opioid analgesic. Additionally, pronounced antipyretic effects were observed at 600 mg/kg, comparable to paracetamol. Using LC-MS/MS, we identified 15 secondary metabolites that most likely contributed to the obtained biological activities. Altogether, our findings indicate that P. perfoliatus has anti-inflammatory, antioxidant, analgesic and antipyretic effects, thus supporting its traditional use and promoting its valorization as a potential candidate in treating oxidative stress-associated diseases.

Screening Anti-Inflammatory Effects of Flavanones Solutions.

There are a large number of remedies in traditional medicine focused on relieving pain and inflammation. Flavanones have been a potential source in the search for leading compounds and biologically active components, and they have been the focus of much research and development in recent years. Eysenhardtia platycarpa is used in traditional medicine for the treatment of kidney diseases, bladder infections, and diabetes mellitus. Many compounds have been isolated from this plant, such as flavones, flavanones, phenolic compounds, triterpenoid acids, chalcones, sugars, and fatty acids, among others. In this paper, natural flavanone 1 (extracted from Eysenhardtia platycarpa) as lead compound and flavanones 1a-1d as its structural analogues were screened for anti-inflammatory activity using Molinspiration® and PASS Online in a computational study. The hydro alcoholic solutions (FS) of flavanones 1, 1a-1d (FS1, FS1a-FS1d) were also assayed to investigate their in vivo anti-inflammatory cutaneous effect using two experimental models, a rat ear edema induced by arachidonic acid (AA) and a mouse ear edema induced by 12-O-tetradecanoylphorbol acetate (TPA). Histological studies and analysis of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 were also assessed in AA-inflamed rat ear tissue. The results showed that the flavanone hydro alcoholic solutions (FS) caused edema inhibition in both evaluated models. This study suggests that the evaluated flavanones will be effective when used in the future in skin pathologies with inflammation, with the results showing 1b and 1d to be the best.

Anti-inflammatory and histopathological studies of leaves extracts of Croton bonplandianus in Albino rats.

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used for the treatment and prevention of inflammation with the increase in number of side effects. Traditional plants have been used to treat inflammation owing to lesser adverse responses. Croton bonplandianus being an anti-inflammatory plant is extensively utilized all over the world. The methanolic and aqueous leaves extracts of Croton bonplandianus were exposed to anti-inflammatory activity in the carrageenan induced paw edema against standard diclofenac sodium, followed by the histopathlogical examination. The highest dose of methanolic extract were shown significant anti-inflammatory action having a significant P-value (P<0.05-0.001) compared with the diclofenac sodium (P<0.01-0.001) and aqueous extracts (P<0.5-0.01). The histopathological examination illustrated the vasodialation with reduction in the intensity of edema, neutrophils infiltration and other inflammatory cells. C. bonplandianus being a reactive oxygen species scavenger, responsible to exert an excellent anti-inflammatory activity. The present study confirmed the anti-inflammatory potential of drug extracts and authors recommended its utilization in the treatment of pain, inflammation and relevant diseases in future. However, phytochemical screening is to be required for the complete evaluation of active chemical constituent (s).