Inhibition Of Edema Research Articles

Chemical characterization, anti-struvite crystal, anti-inflammatory, analgesic, and antidepressant activities of Papaver rhoeas L. root and leaf extracts

Ethnopharmacological relevancePapaver rhoeas L. (P. rhoeas) is used to treat a wide range of pathologies. But there is no data on the anti-struvite, anti-inflammatory, analgesic, and anti-depressant effects of root and leaf extracts from this medicinal plant.Aim of the study: This study aimed to chemically characterize and determine the antidepressant, analgesic, anti-inflammatory, and anti-struvite activities of the root extract (RE) and leaf extract (LE) of P. rhoeas, a wild plant. Materials and methodsThe extraction of secondary metabolites and phytochemical screening were carried out using standard methods. The anti-struvite effect of our samples was assessed by Fourier transform infrared spectroscopy (FT-IR) and microscopic observation. For the anti-inflammatory impact, we used the carrageenan-induced paw edema technique in rats. To assess the analgesic effect of the extracts, we recorded the resulting abdominal contraction after intraperitoneal (IP) acetic acid injection. Finally, we assessed the antidepressant effect by conducting the Forced Swimming Test (FST). ResultsPhytochemical screening results revealed the presence of phenols, flavonoids, saponins, tannins, coumarins, terpenoids, and alkaloids. Extraction results confirmed that our extracts were rich in secondary metabolites. Both P. rhoeas extracts limited struvite crystal development by reducing the size and number of crystals, as indicated by FT-IR analysis and microscopic observation. Additionally, the anti-struvite effects of the LE sample were greater than those of the RE sample. The results of the anti-inflammatory capacity of our extracts demonstrate the maximum inhibition of carrageenan-induced edema following 6 h (T6) of injection, ranging from 72.73 ± 7.7% for LE (400 mg/kg) to 95.45 ± 6.42% for the RE sample (400 mg/kg). On the other hand, the results for analgesic activity showed that the number of abdominal contractions in rats treated with RE and LE ranged from 11 ± 1.73 for RE (400 mg/kg) to 18 ± 1.50 for LE (200 mg/kg), while that of aspirin was 10.33 ± 0.57. Furthermore, the FST results show that the immobility time in rats treated with RE and LE varied from 91.98 ± 4.24 s for LE-treated rats (300 mg/kg) to 123.54 ± 7.83 s for RE-treated rats (150 mg/kg). ConclusionBased on these results, the roots and leaves of the studied plant can be considered a significant source of biologically active molecules for use in the pharmaceutical industry.

Standardized seed extract of Cajanus cajan (L) Millsp. produced antinociceptive and anti-inflammatory actions through inhibition of inflammatory mediators and activation of opioidergic signaling

Background and PurposePeripheral tissue damage and diseases could lead to persistent pain beyond possible resolution suggestive of disease-promoting condition which gives rise to chronic pain. The inability of current medications to manage some chronic inflammatory and painful conditions necessitate the need for better treatment options. Natural products have been a veritable source for the discovery of more efficacious and safer therapeutics. Cajanus cajan (L) Millsp, (Fabaceae) is used in traditional African medicines for the treatment of painful, gut disturbance and inflammatory conditions. Hence, the current study aims to investigate the anti-inflammatory and antinociceptive actions of the ethanol seed extract of Cajanus cajan (CC) in rodents and possible mechanisms of action. MethodsHigh performance liquid chromatography coupled with diode-array detection (HPLC-DAD) was used to identify 8 major flavonoids in CC. Antinociceptive activity was investigated using the acetic acid-induced writhing reflex, biphasic formalin-induced flinching behaviour and supraspinal hot plate-evoked nociception in mice. Carrageenan-induced rat paw oedema test was used to evaluate the anti-inflammatory action of CC in rats. Possible mechanism of antinociception and anti-inflammatory actions were examined using both in vivo model and molecular docking procedures against µ-opioid receptor (MOR), cyclooxygenase-2 (COX-2) and phospholipase A2 (PLA2) proteins, respectively. ResultsThe chromatographic procedure qualitatively and quantitatively confirmed the presence of rutin, quercetin, gallic acid, luteolin, pinostrobin, BiochaninA, formononetin and apigenin in CC. The in vivo nociceptive assay, showed that CC (50, 100, or 200 mg/kg, p.o.) significantly decreased mean number of writhing reflex with peak effect at 50 mg/kg (72% inhibition) when compared with vehicle control in mouse writhing test. Similarly, the biphasic formalin-induced nociception was significantly reduced by CC (50 mg/kg) with 24.61 and 66.73% inhibition of nociceptive reactions in both the early and late phases of formalin-induced inflammatory pain, respectively. In addition, CC significantly increased supraspinal thermally mediated pain threshold with maximum possible effects of 42.25 and 52.16% at CC 50 and 100 mg/kg, respectively, in hot-plate test. Similarly, CC100mg/kg caused time course inhibition of carrageenan-induced paw oedema in rat with peak effect (65.78%, CC 100 mg/kg; 6 h). Interestingly, the antinociceptive action of CC was blocked by the pre-treatment of mice with l-NG-nitro arginine methyl ester (L-NAME) or naloxone. The molecular docking analysis revealed prominent interactions of pinostrobin, physcion and lupeol with MOR, COX-2, and PLA2, respectively. ConclusionFindings from this study showed that Cajanus cajan seeds extract possesses anti-nociceptive and anti-inflammatory through inhibition of inflammatory mediators (PLA2/COX-2) and activation of opioidergic signalling.

Anti-inflammatory Activity and Cyclooxygenase-2 Inhibitory effect of Peperomia pellucida (L.) Kunth Extract

Inflammation is an adaptive response underlying a wide variety of physiological and pathological processes mediated by the Cyclooxygenase (COX) enzyme. Cyclooxygenase-2 (COX-2) is an important enzyme that catalyzes the production of prostaglandins from arachidonic acid and has a crucial role in various pathologies including inflammation, neurological disorders, and cancer. The selective suppression of COX-2 over COX-1 is thought to be a useful approach for treating inflammation. Peperomia pellucida (L.)Kunth has been traditionally used as an anti-inflammatory and antioxidant, thus giving scope for anti-inflammatory studies. Since the action of Ethanol extract of Peperomia pellucida (EEPp) on COX-2 has not been previously described, in this study, we further investigated the effect of Cyclooxygenase-2 inhibitory effects spectrophotometrically in ELISA readers and evaluated of anti-inflammatory activity in the carrageenan-induced rat paw edema model. The edema volume was measured using a plethysmometer. The results showed that the EEPp (100, 200, and 400mg/kg BW) had significant anti-inflammatory activity and the EEPp demonstrated a COX-2 Inhibitory effect. The percentage of COX-2 inhibition was 10.87%, 47.04%, 56%, and the percentage of inhibition of paw edema was 34.93%, 46.61%, and 64.04%, respectively. These findings suggest that Peperomia pellucida extracts possess promising and remarkable anti-inflammatory activity, which is directed against the enzymatic activity of COX-2.

Antiinflammatory, Antinociceptive and Antioxidant activities of aqueous and methanolic stem bark extracts of Fagaropsis hildebrandtii (Engl.) Milne-Redh. (Rutaceae)

Background: Fagaropsis hildebrandtii has been widely used in African traditional medicine to treat various illnesses, particularly those associated with inflammation, pain and oxidative stress. However, experimental data on the anti-inflammatory, anti-nociceptive and antioxidant of the different parts of F. hildebrandtii is still limited. Objectives: The objectives of this study were to determine the phytochemical composition, anti-inflammatory, antinociceptive and antioxidant activities of stem bark extract of F. hildebrandtii from Makueni County, Kenya. Materials and Methods: The stem bark of F. hildebrandtii was extracted by maceration using water and methanol. Standard qualitative methods were then used to determine the presence or absence of various phytochemicals in the extracts. Total phenolic and flavonoid contents were determined by Folin-Ciocalteu and aluminium chloride calorimetric methods, respectively. Anti-inflammatory and anti-nociceptive activities of increasing water and methanol extracts doses (2-250mg/Kg) were tested using carrageenan-induced paw edema and acetic acid-induced writhing animal models, respectively in comparison with dexamethasone and aspirin as standard. Antioxidant activities of plant extracts were assayed by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) method, with ascorbic acid as the standard. Data analysis was conducted by two-way ANOVA with appropriate post hoc tests. Statistical significance level was set at p ≤ 0.05. Results: Phenols, flavonoids, alkaloids, saponins, tannins, terpenoids and coumarin were detected in the extracts. However, anthocyanins and anthraquinones were absent in both water and methanolic extracts. Notably, methanol extract had a high total phenolic level compared to water extract (34.590 ± 2.490 mgGAE/g vs. 7.893 ± 1.619 mgGAE/g; p<0.05). Total flavonoid content of F. hildebrandtii methanol extract was also higher in comparison to water extract (132.18 ± 0.26 mgCE/g vs. 42.68 ± 0.93mgCE/g; p<0.05). F. hildebrandtii water and methanol extracts had a radical scavenging activity IC50 of 0.98 µg/ml and 0.987 µg/ml respectively, which was significantly lower than 5.674 µg/ml for ascorbic acid, indicating a higher antioxidant potency. The percentage inhibition of carrageenan-induced hind paw edema by F. hildebrandtii extracts was not significantly different in comparison with 10 mg/Kg of dexamethsone standard over a 5-hour test period (p>0.05). F. hildebrandtii water and methanol extracts exhibited a dose-dependent inhibition of acetic acid-induced writhing in mice, reaching a maximum of 53.1 ± 6.1% and 80.24 ± 12.59%, respectively, at 250 mg/Kg. Notably, the percentage inhibition of acetic acid-induced writhing by 50 mg/kg and 250 mg/kg of F. hildebrandtii methanolic extract was similar to that of aspirin standard at 150 mg/kg (77.75 ± 19.64% vs. 80.24 ± 12.59% vs. 84.99 ± 3.26%, p>0.05, two-way ANOVA). Conclusion: F. hildebrandtii has anti-inflammatory, antinociceptive and antioxidant activities. These findings validate the use of F. hildebrandtii crude extracts among Kenyan ethnic groups in management of diseases associated with inflammation, pain, and oxidative stress.

PRELIMINARY INVESTIGATIONS ON DIOSPYROS MALABARICA LEAVES EXTRACTS FOR ANTI-INFLAMMATORY AND WOUND HEALING ACTIVITY

The present study aimed to screen different extracts of Diospyros malabarica leaves for antiinflammatory and wound-healing effect in mice. Phytochemical screening of different extracts i.e. petroleum ether, chloroform, ethyl acetate, ethanol and aqueous extracts, were performed using different chemical test. All extracts were subjected to study antiinflammatory effects using xylene-induced edema and wound healing activity using an incision wound model. Antiinflammatory potential was recorded by observing the mice’s percent inhibition of edema, nitric oxide (NO) estimation, and myeloperoxidase (MPO) action. The wound healing effect was observed by measurement of tensile strength, protein level and hydroxyproline level in the wound tissues. Observation of phytochemical study was confirmed that ethanolic extract of D. malabarica leaves contains glycosides and flavonoids as major chemical constituents. Antiinflammatory effect was confirmed by significant (p<0.05) percent inhibition of ear edema, significant reduction of NO level and MPO level of mice by ethanol extract of D. malabarica leaves. Wound healing potential was observed by the significant increase in tensile strength of wound tissue after treatment with ethanolic extract. A significant (p<0.05) increase in protein and hydroxyproline level of tissue were observed after treatment with ethanolic extract of D. malabarica. In conclusion, the potent antiinflammatory and wound healing effects of ethanolic extract of D. malabarica may be observed due to the presence of glycoside and flavonoid components.

Uji Aktivitas Antiinflamasi Estrak Sirih Cina (Peperomia Pellusida) Pada Tikus Jantan Galur Wistar Yang Diinduksi Karagenan

Chinese betel plant (Peperomia pellucida), an herbal plant belonging to the Piperaceae family, Chinese betel plant (Peperomia pellucida). Research Stages: sample collection, extract preparation, extract standardization, determination of non-specific parameters, phytochemical screening, preparation of test solutions, anti-inflammatory activity tests, treatment of test animals. The results of maceration were filtered using filter paper, then the entire filtrate was concentrated using a vacuum evaporator and water bath at 60℃ to obtain a thick extract. The yield of 96% ethanol extract from Chinese betel powder (Peperomia pellucida) obtained was 4.531%. Based on the results, it has non-specific characteristics, namely drying shrinkage of 9.26%, ash content of 7.9% and water content of 4.15%. Phytochemical screening the compound tested was positive, A dose of 150 mg/kgBB is also an effective dose in inhibiting the formation of edema seen from the effect it gives is stable and has the highest percentage of edema inhibition compared to other doses, which is 34,35%.

Blocking the major inflammatory pathways by newly synthesized thiadiazine derivatives via in-vivo, in-vitro and in-silico mechanism

A series of new thiadiazine derivatives including 2-(5-alkyl/aryl-6-thioxo-1,3,5-thiadiazinan-3-yl) propanoic acids (a) and 4-methyl-2-(5-alkyl/aryl-6-thioxo-1,3,5-thiadiazinan-3-yl) pentanoic acids (b) were synthesized by reacting primary alkyl/aryl amines with CS2, followed by reaction with formaldehyde and amino acids. The chemical structures of synthesized compounds were confirmed by 13C- NMR and 1H- NMR techniques. The inhibitory potential of major inflammatory enzymes, COX-2 and 5-LOX was examined. Moreover, anti-nociceptive and anti-inflammatory activities were evaluated in the in vivo thermally induced nociceptive, and carrageenan induced paw edema models in mice. The in-vitro results reflect that these compounds exhibited concentration dependent inhibition of COX-2 and 5-LOX. The tested compounds at 50 mg/kg showed significant effect on thermally induced pain, and reduced latency time (seconds) as compared to the vehicle treated animals. Moreover, tested compounds exhibited percent inhibition of paw edema in the carrageenan induced paw edema model in mice. Furthermore, the binding modes of the most active COX-2 and 5-LOX inhibitors were determined through computational methods. The computational study reflects that the docked compounds have high binding affinities for COX-2 and 5-LOX enzymes, which leads to inhibition of these enzymes.

EVALUATION OF THE ACUTE TOXICITY, ANTI-INFLAMMATORY AND ANALGESIC ACTIVITIES OF FOUR PLANTS USED IN THE BENINESE PHARMACOPOEIA (ANNONA SENEGALENSIS, SARCOCEPHALUS LATIFOLIUS, COMBRETUM GLUTINOSUM AND DETARIUM MICROCARPUM)

Inflammation and pain are a common feature of almost all non-communicable diseases. Annona senegalensis, Sarcocephaluslatifolius, Combretum glutinosum and Detariummicrocarpum have been traditionally used to treat different types of diseases. This study aimed to evaluate in-vivo anti-inflammatory and analgesic activities of these plants extracts, as well as their acute toxicity. The hydroethanolic extracts of the leaves were used for in-vivo tests on Wistar rats. The anti-inflammatory activity was evaluated by the 2% formalin-induced edema test, while the analgesic activity was evaluated by the acetic acid test. The acute toxicity of the crude hydroethanol extract was evaluated by oral administration of the extract to Wistar rats. A single dose of 2000 mg/kg body weight was administered and the effects on biochemical parameters were evaluated. The two plants tested showed a significant analgesic activity with a percentage of inhibition of cramps of 85.37 % for D. microcarpum and 87.37 % for A.senegalensis compared to aspirin which is 45.07%. The percentage of edema inhibition at 100 mg/kg reached 37.47 % for Detariummicrocarpum and 68.0 % for Annona senegalensis against 34.10 % for diclofenac. The toxicity test performed on rats by the oral route at a dose of 2000 mg/kg body weight showed no adverse effects and no deaths during the 14 days of observation.

Anti-inflammatory and Analgesic Effects of Aqueous and Methanol Leaf Extracts of Chrysophyllum Albidum in Male Wistar Rats with Acetic Acid Induced Inflammation and Pain

Chrysophyllum albidum (African star apple) fruits and fresh leaves have been used as food widely. The mature leaves, bark, seeds and roots are used as folk medicine for the treatment and management of various ailments, hence the anti-inflammatory and analgesic properties of Chrysophyllum albidumon inflammation and pain were investigated. Thirty five male wistar rats weighing 150.41±13.27g were randomly placed in seven (I-VII) groups. Group I (normal control), group II (diclofenac), group III(positive control), groups IV and V received 200mg and 400mg/Kg bodyweight of methanolic extract; groups VI and VII received 200mg and 400mg/Kg bodyweight of aqueous extract, respectively. 0.1ml of 2.5% of acetic acid was injected into the hind paw of rats to induce inflammation and pain, and then treated for 14 days. Severity of pain was quantified using Likert scale. Standard biochemical and phytochemical parameters were determined. Statistical differences in the mean between groups was compared using one way analysis of variance at p<0.05. The extract had inhibition of edema at 92%, 95% and 92%, 93% at doses of 200mg/kg, 400mg/kg bodyweights of methanolic and aqueous extracts, respectively. The yield from quantitative analysis ranged from Cardiac glycosides>Saponins>flavonoids>alkaloids>phenols; 42.6% vs. 38.1% for methanolic vs. aqueous extracts, respectively. Animals treated with both extracts had significant increase in weights and white blood cells compared to the standard and normal control group (p<0.05). These suggest that the extract had ameliorative, preventive and curative potency on inflammation which may be attributed to the presence of glycosides, saponins and other phytoconstituents.

Papaver rhoeas L. stem and flower extracts: Anti-struvite, anti-inflammatory, analgesic, and antidepressant activities

The Papaver rhoeas L. (P. rhoeas) plant, which belongs to the Papaveraceae family, is also used as food and is exploited to treat several health problems. The purpose of this research is to determine the anti-struvite, anti-inflammatory, analgesic, and antidepressant effects of the stem extract (SE) and flower extract (FE) of the plant P. rhoeas. We used polarizing microscopy and Fourier transform infrared spectrometry (FT-IR) to evaluate the anti-struvite effect of our plant. The edema approach induced by the carrageenan molecule was used to study the anti-inflammatory impact of our extracts. The analgesic test was determined by calculating the number of abdominal contractions induced by the intraperitoneal (IP) administration of acetic acid. To evaluate the antidepressant effect of our extracts, we used the forced swimming test (FST). According to the results of the secondary metabolite extraction, both extracts contained high contents of secondary metabolites, while the results of the screening test showed that flavonoids, alkaloids, phenols, tannins, coumarins, saponins, and terpenoids were present. The result of struvite crystallization inhibition observed by polarizing microscopy and FT-IR shows the inhibition of struvite crystal aggregation by SE by decreasing the amount and size of crystals in a manner similar to cystone. The results of anti-inflammatory activity show maximum inhibition of edema after six hours of carrageenan injection in rats (T6) for all extracts, with a maximum value of 86.36% for SE at the dose of 200 mg/kg. Regarding the analgesic effect of our plant, the lowest number of abdominal contractions was observed in rats treated with SE at a dose of 400 mg/kg. The FST results show that the lowest immobilization time was observed in rats treated with FE at a dose of 400 mg/kg. The results obtained show that the flowers and stems of P. rhoeas can constitute a rich source of bioactive molecules with potential pharmaceutical applications.

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

Ethnopharmacological relevanceInflammation 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 studyIn 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 methodsFB 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. Results100 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-1β, 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. ConclusionIn conclusion, FB might be used as an effective and potent drug against inflammation.

Isolation of alkaloidal and glycosidal fractions from leaves of Trigonella foenum-graecum L. cv. Desi indigenous to Pakistan for antiprostaglandin evaluation as substitute of nonsteroidal anti-inflammatory drugs

Ethnopharmacological relevanceTrigonella foenum graecum (fenugreek) has been in use for a long time as a traditional medicine and natural food additive. The reported gastro-protective property makes it unique among other herbs. Seeds and leaves have been shown to exert significant antiatherogenic, antidiabetic, antianorexic, antioxidant, anticarcinogenic, antihyperlipidemic, galactogogue and anti-inflammatory effects in several animal and human models. But its use as a substitute for ulcerative nonsteroidal anti-inflammatory drugs needs to be confirmed. Aim of the studyNonsteroidal anti-inflammatory drugs (NSAIDs) are in common use in treating inflammation associated with a variety of ailments, fever and pain such as menstrual cramps, back pain, arthritic pain and headaches. Their toxicity profile includes the risk of severe gastro-intestinal adverse events like increased bleeding tendency, ulceration, perforation, etc. Conventional NSAIDs have also been reported to reduce the glomerular filtration rate (GFR) by affecting afferent arterioles in nephrons. Exacerbated potassium levels were noted in patients using NSAIDs concomitantly with antihypertensive drugs belonging to the angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) classes. In this context, the need of the hour is to discover and isolate new compounds from the reported medicinal plants for evaluation of antiprostaglandin potential and safety profile in terms of the hepato-renal system. These compounds may be used as substitutes for NSAIDs in the future management of inflammation and pain with therapeutic equivalency and organ safety. In this scenario, the present study aimed to assess the antiprostaglandin potential of alkaloidal and glycosidal fractions from the leaves of Trigonella foenum-graecum L. cv. Desi variety, indigenous to Pakistan, in albino mice along with safety profile. The herb has been used as folk medicine since ancient times for treating inflammation and pain. Material and methodsAlkaloidal and glycosidal fractions were separated from a methanol extract of leaves of the fenugreek Desi variety. After separation of fractions, their subsiding effects on carrageenan-induced inflammation, air pouch exudate prostaglandin-E2 levels, Brewer's yeast induced pyrexia and acetic acid induced abdominal constrictions were assessed in adult male albino mice. The safety profile of fractions was assessed by measuring their effects on mice sera hepato-renal biomarkers. ResultAlkaloidal fraction of T. foenum Desi variety was found to be significantly effective in reducing inflammation, air pouch exudate PGE2 levels, fever (≤37 °C) and pain by inhibiting writhes (up to 96.58%) Gradual inhibition of paw edema was observed 1–6 h post-dose, with maximum reduction percentages of 62.82% and 62.57% for 100 mg and 200 mg, respectively. Both fractions did not disturb the normal physiology of the hepato-renal system by showing normal biomarker values. ConclusionIn summary, the results demonstrate the potent antiprostaglandin potential of the alkaloidal fraction of gastroprotective fenugreek “Desi” leaves with hepato-renal system safety and hence justify its use as a substitute for ulcerative nonsteroidal anti-inflammatory drugs.

Antioxidant, Anti-Inflammatory, and Anti-Cancer Properties of Amygdalin Extracted from Three Cassava Varieties Cultivated in Benin.

Given that cancer is a disease that is rampant in the world and especially in Africa, where the population has enormous difficulty treating it, plants are a safer and less expensive alternative. Cassava is a plant species valued in Benin because of its numerous medicinal and nutritional virtues. This study evaluated the biological activities of amygdalin from the organs of three cassava varieties most commonly produced in Benin (BEN, RB, and MJ). HPLC analysis was used to quantify amygdalin in cassava organs and derivatives. Phytochemical screening was performed to determine secondary metabolite groups. DPPH and FRAP methods were used to assess antioxidant activity. Cytotoxicity of the extracts was tested on Artemia salina larvae. The anti-inflammatory activity was evaluated in vivo in an albino mouse paw edema model induced by 5% formalin. The anticancer activity was evaluated in vivo on Wistar rats rendered cancerous by 1,2-dimethylhydrazine (DMH) using 5-fluorouracil as a reference molecule. The results showed that the organs of all three-cassava varieties contained glycosides, flavonoids, saponosides, steroids, tannins, coumarins, and cyanogenic derivatives. Young stems and fresh cassava leaves had the highest amygdalin concentrations, with 11,142.99 µg 10 g-1 and 9251.14 µg 10 g-1, respectively. The Agbeli derivative was more concentrated in amygdalin, with a content of 401.56 µg 10 g-1 than the other derivatives. The antioxidant activity results showed that the amygdalin extracts were DPPH radical scavengers with IC50 values ranging from 0.18 mg mL-1 to 2.35 mg mL-1. The cytotoxicity test showed no toxicity of the extracts toward shrimp larvae. Administration of amygdalin extracts from the leaves of BEN and MJ varieties prevents inflammatory edema. The percentages of edema inhibition varied between 21.77% and 27.89%. These values are similar (p > 0.05) to those of acetylsalicylic acid (25.20%). Amygdalin extract of the BEN variety significantly (p < 0.0001) reduces edema. Both BEN extracts inhibited cancer induction with DMH. In preventive and curative treatments, rats fed with amygdalin extracts showed low anti-cancer activity under the effect of DMH and a significant difference in biochemical results. Thus, the organs of all three cassava varieties studied have secondary metabolites and good antioxidant activity. The leaves contain high levels of amygdalin and can be used as anti-inflammatory and anticancer agents.

Supramolecular complexes between Plinia cauliflora (DC.) Kausel extracts and β-cyclodextrin: Physicochemical characterization and antioxidant and anti-inflammatory properties

This work aims to investigate the supramolecular complexes formation between β-cyclodextrin (βCD) and compounds present in leaves (EEL) and branches (EEB) of Plinia cauliflora (DC.) Kausel Physicochemical characterization was carried out to investigate the formation of supramolecular complexes (EEL/βCD and EEB/βCD), such as, Fourier-transform infrared (FTIR) spectroscopy, thermal analysis (TGA/DTA), scanning electron microscopy (SEM), dynamic light scattering (DLS), Zeta potential (ZP), and electrical conductivity measurements. Antioxidant activity was evaluated by the 2,2-diphenyl-1-picrylhydrazyl, β-carotene/linoleic acid, and thiobarbituric acid reactive substance assays. Finally, anti-inflammatory activity was investigated by nitric oxide (NO) determination and evaluation of ear edema inhibition. FTIR spectroscopy and TGA/DTA confirmed the interactions in the solid-state, while ZP and DLS showed that the interaction between extracts and βCD caused differences in the hydrophobic nanoprecipitates. Moreover, the SEM micrograph of EEL/βCD and EEB/βCD indicates changing in particle morphology which confirms the interactions between extract compounds and βCD. EEL/βCD and EEB/βCD showed promising antioxidant activity for all assays performed. Furthermore, anti-inflammatory activity was confirmed by a significant reduction of NO (maximum of 90 and 85% for EEL/βCD and EEB/βCD, respectively) and inhibition of ear edema above 93% for both phytocomplexes. The development of a formulation based on the molecular encapsulation of extracts from P. cauliflora with βCD could be an effective, safe, and sustainable therapeutic alternative. Therefore, our samples showed the ability to reduce oxidative stress and inflammation, and serve as potential anti-inflammatory agents.

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 and analgesic potentials of fermented Citrullus vulgaris with mutant and non-mutant strains of Bacillus subtilis to produce condiment (ogiri)

BackgroundOxidative stress leading to degenerative diseases has become the leading cause of health issues. The use of non-steroidal anti-inflammatory drugs have be associated with complications. The development of nutraceuticals/functional foods that can modulate oxidative stress becomes very necessary. Mutated Bacillus subtilis (B. subtilis) have been reported to produce D-ribose, having ameliorative effects on pro-inflammatory cytokine and increased ATP synthesis. AimsThe present study investigated analgesic and anti-inflammatory effects of ogiri samples fermented with mutant (modified) and non-mutant strains of B. subtilis in α-carrageenan-induced rats. MethodsInflammation and pain were induced via α-carrageenan, while indomethacin and ogiri samples were used for treatment. Mobility and inflammatory volumes, pro-inflammatory cytokines, E-NTPDase activities, antioxidant activities and levels, hepatic and renal markers were investigated. ResultsIt was shown that some of the ogiri fermented with mutant strains of Bacillus subtilis samples ameliorated α-carrageenan-induced inflammatory oedema and painful movements. The percentage inhibition ranged from 18.69 ± 1.98–66.35 ± 2.97, with high percentage inhibition of oedema observed with samples IDC22, AAC70, AAC65, AAH22, AAD10, AAD51, and AAD30 (67.02 ± 1.98, 66.35 ± 2.97, 61.21 ± 2.31, 63.55 ± 1.32, 61.22 ± 2.31, 59.81 ± 0.66 and 59.35 ± 2.32) respectively. The reduction rate and mobility ranged from 5.30 to 10.40 mm and 169.00–288.50 min. The samples mentioned above also showed better amelioration with reduction rates (10.4, 9.85, 9.65, 10.1, 9.85. 9.85 and 9.70), and mobility values (257.00, 273.50, 261.00, 268.00, 271.50, 258.50, and 257.50) than other samples. The E-NTPDase activity ranged from 10.191 to 13.369 and showed energy restoration on some ogiri samples AAC70, AAC65, AAC22, AAH22, AAD10, AAD51, and AAD30 (12.558, 11.882, 11.288, 11.242, 12.324, 11.807 and 11.616) compared to the standard drug (9.798). Pro-inflammatory cytokines, inflammatory markers, antioxidants, hepatic and renal enzymes, and concentrations altered were restored in the same samples mentioned above. ConclusionThe modified ogiri samples, especially AAC70, can be applied as analgesic and anti-inflammatory agents.

Synthesis and biological evaluation of resveratrol amide derivatives as selective COX-2 inhibitors

Selective COX-2 inhibitors have been considered to be reliable alternatives to tNSAIDs, but most of them were withdrawn from the market due to their risk of heart attack and stroke. Therefore, it is urgent to develop a new type of selective COX-2 inhibitor with high efficiency and low toxicity. Inspired by the cardiovascular protection, and anti-inflammatory activity of resveratrol, we synthesized 38 resveratrol amide derivatives and evaluated their COX-1/COX-2 inhibitory activities. Compounds 8a, 6a, 8c and 13c showed important inhibitory activity against COX-2 (IC50 = 0.42–2.54 μM) with definite selectivity (SI = 48–83). Molecular docking study demonstrated that these compounds partially entered the 2°-pocket of the COX-2 active site and interacted with the amino acid residues responsible for the COX-2 selectivity, which was in a similar orientation and binding interactions to rofecoxib. Further anti-inflammatory activity evaluation in vivo of these active compounds revealed that compound 8a showed no gastric ulcer toxicity, and displayed evident anti-inflammatory effect (45.95% inhibition of edema) with three oral doses of 50 mg/kg, which is worthy of further study. Moreover, compounds 6a and 8c also exhibited superior gastric safety profiles compared to the reference drugs celecoxib and indomethacin.

In vitro and in vivo anti-inflammatory activity of Cupressus torulosa D.DON needles extract and its chemical characterization

Ethnopharmacological relevanceCupressus torulosa (family Cupressaceae), widely distributed in the north western Himalayan region of India, is a coniferous aromatic tree with various traditional uses of its aerial parts. Its needles have been used for anti-inflammatory, anticonvulsant, antimicrobial, and wound-healing properties. Aim of the studyThe study aimed at investigating the previously unknown anti-inflammatory activity of the hydromethanolic extract of the needles employing in vitro and in vivo assays and scientifically validate traditional claim of their use in treatment of inflammation. Chemical characterization of the extract with the aid of UPLCQTOFMS was also of interest. Materials and methodsC. torulosa needles were first defatted with hexane and sequentially extracted with chloroform and 25% aqueous methanol (AM). Since the presence of phenolics (TPCs, 208.21 ± 0.95 mg GAE/g needles) and flavonoids (TFCs, 84.61 ± 1.21 mg QE/g needles) was observed in the AM extract only, it was chosen for biological and chemical examinations. Acute toxicity of the AM extract on female mice was evaluated following the OECD guideline 423. In vitro anti-inflammatory activity of the AM extract was examined using egg albumin denaturation assay while carrageenan-induced paw edema and formalin-induced paw edema models at doses of 100, 200 and 400 mg/kg po were used to determine the in vivo activity of the AM extract on Wistar rats of either sex. The components of the AM extract were analyzed by UPLC-QTOF-MS method using non-targeted metabolomics approach. ResultsAM extract was found to be non-toxic at 2000 mg/kg b.w. with no signs of abnormal locomotion, seizures and writhing. The extract demonstrated promising in vitro anti-inflammatory activity (IC50 160.01 μg/mL) compared to standard diclofenac sodium (IC50 73.94 μg/mL) in egg albumin denaturation assay. In carrageenan-induced paw edema and formalin-induced paw edema tests the extract showed significant anti- inflammatory activity (57.28% and 51.04% inhibition of paw edema, respectively) at the dose of 400 mg/kg p.o. after 4 h in comparison to the standard diclofenac sodium which displayed 61.39% and 52.90% inhibition, respectively, at the dose of 10 mg/kg p.o. after 4 h in these models. A total of 63 chemical constituents, majority of them being phenolics, were found in the AM extract of the needles. Two compounds namely monotropein (iridoid glycoside), (±)12-HETE (eicosanoid) and fraxin (coumarin glycoside) were reported to have anti-inflammatory effect. ConclusionsFor the first time our study demonstrated that hydro-methanolic extract of C. torulosa needles exhibit anti-inflammatory activity thereby supporting their traditional use in the treatment of inflammatory disorders. UPLCQTOFMS assisted chemical profile of the extract was also unveiled.

Astaxanthin ameliorates spinal cord edema and astrocyte activation via suppression of HMGB1/TLR4/NF-κB signaling pathway in a rat model of spinal cord injury.

Spinal cord edema is a quick-onset phenomenon with long-term effects. This complication is associated with inflammatory responses, as well as poor motor function. No effective treatment has been developed against spinal edema, which urges the need to provide novel therapies. Astaxanthin (AST) is a fat-soluble carotenoid with anti-inflammatory effects and a promising candidate for treating neurological disorders. This study aimed to investigate the underlying mechanism of AST on the inhibition of spinal cord edema, astrocyte activation, and reduction of inflammatory responsesin a rat compression spinal cord injury (SCI) model. Male rats underwent laminectomy at thoracic 8-9, and the SCI model was induced using an aneurysm clip. After SCI, rats received dimethyl sulfoxide or AST via intrathecal injection. The effects of AST were examined on the motor function, spinal cord edema, integrity of blood-spinal cord barrier (BSCB), and expression of high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), glial fibrillary acidic protein (GFAP), and aquaporin-4 (AQP4), and matrix metallopeptidase- 9 (MMP-9) post-SCI. We showed that AST potentially improved the recovery of motor function and inhibited the spinal cord edema via maintaining the integrity of BSCB, reducing the expression of HMGB1, TLR4, and NF-κB, MMP-9 as well as downregulation of astrocyte activation (GFAP) and AQP4 expression. AST improves motor function and reduces edema and inflammatory responses in the spinal tissue. These effects are mediated by suppression of the HMGB1/TLR4/NF-κB signaling pathway, suppressing post-SCI astrocyte activation, and decreasing AQP4 and MMP-9 expression.

Anti-Inflammatory and Neuroprotective Effects of Standardized Fractions in Herniarin and Daphnoretin from Distictis buccinatoria.

Distictis buccinatoria is used for inflammatory-related diseases. From a dichloromethane extract were obtained five different fractions called F1 to F5, and sub-fractions F4-1, F5-1, F5-2, and F5-3; and were evaluated as anti-neuroinflammatory, antioxidant, and nootropic agents in mice exposed to lipopolysaccharide. Also, were isolated herniarin, daphnoretin, and fraction's terpenes with an anti-inflammatory activity using 12-O-tetradecanoylphorbol-13-acetate-induced auricular edema. The inhibition of local edema was: F1 (73.6 %), F2 (57 %), F3 (62.61 %), F4 (87.3 %), and F5 (93.57 %). Terpene fraction inhibited at 89.60 %, herniarin at 86.92 % (Emax 99.01 %, ED50 0.35 mg ear-1 ), and daphnoretin at 86.41 %. Fractions F4-1 and F5-2 (10 mg kg-1 ) enhancer spatial memory acquisition and spontaneous motor activity; reduced IL-1β, TNF-α, and IL-6; increased IL-10, enhanced the activity of CAT and GR. D. buccinatoria has neuroprotective activity and contains daphnoretin and herniarin, with anti-inflammatory activity.