Evaluation Of Anti-inflammatory Activity Research Articles

Evaluation of Anti-Inflammatory and Anti-Arthritic Activities of AV11-03 in Female Rats

Rheumatiod arthritis is a systemic auto-immune disease characterized by chronic inflammation at multiple synovial joints, cartilage destruction and bone erosion. Currently available non-steroidal anti-inflammatory drugs, cortico-steroids and disease modifying anti-rheumatic therapies have severe side effects on prolonged use and thus throw a challenge for development of safe, effective alternatives. Of the many plant drugs claimed to be effective in the treatment of rheumatoid arthritis, in depth studies were carried out on the fruits of Terminalia chebula (Haradae) and the oleo-gum resin of Boswellia serrata (Sallaki). Glucosamine was shown to be chondrio-protective and effective in osteo-arthritis. Hence, we tested ‘AV-11 03’ which is a combination of the extracts of haradae, salliki an maize glucosamine on acute and chronic inflammatory models by studying a battery of physical, biochemical, histological and radiological parameters.

Identification of Novel Cyclooxygenase-1 Selective Inhibitors of Thiadiazole-Based Scaffold as Potent Anti-Inflammatory Agents with Safety Gastric and Cytotoxic Profile.

Major obstacles faced by the use of nonsteroidal anti-inflammatory drugs (NSAID) are their gastrointestinal toxicity induced by non-selective inhibition of both cyclooxygenases (COX) 1 and 2 and their cardiotoxicity associated with a certain class of COX-2 selective inhibitors. Recent studies have demonstrated that selective COX-1 and COX-2 inhibition generates compounds with no gastric damage. The aim of the current study is to develop novel anti-inflammatory agents with a better gastric profile. In our previous paper, we investigated the anti-inflammatory activity of 4-methylthiazole-based thiazolidinones. Thus, based on these observations, herein we report the evaluation of anti-inflammatory activity, drug action, ulcerogenicity and cytotoxicity of a series of 5-adamantylthiadiazole-based thiazolidinone derivatives. The in vivo anti-inflammatory activity revealed that the compounds possessed moderate to excellent anti-inflammatory activity. Four compounds 3, 4, 10 and 11 showed highest potency (62.0, 66.7, 55.8 and 60.0%, respectively), which was higher than the control drug indomethacin (47.0%). To determine their possible mode of action, the enzymatic assay was conducted against COX-1, COX-2 and LOX. The biological results demonstrated that these compounds are effective COX-1 inhibitors. Thus, the IC50 values of the three most active compounds 3, 4 and 14 as COX-1 inhibitors were 1.08, 1.12 and 9.62 μΜ, respectively, compared to ibuprofen (12.7 μΜ) and naproxen (40.10 μΜ) used as control drugs. Moreover, the ulcerogenic effect of the best compounds 3, 4 and 14 were evaluated and revealed that no gastric damage was observed. Furthermore, compounds were found to be nontoxic. A molecular modeling study provided molecular insight to rationalize the COX selectivity. In summary, we discovered a novel class of selective COX-1 inhibitors that could be effectively used as potential anti-inflammatory agents.

Nonsteroidal Anti-Inflammatory Drug Conjugated with Gadolinium (III) Complex as an Anti-Inflammatory MRI Agent.

Studies have been actively conducted to ensure that gadolinium-based contrast agents for magnetic resonance imaging (MRI) are accompanied by various biological functions. A new example is the anti-inflammatory theragnostic MRI agent to target inflammatory mediators for imaging diagnosis and to treat inflammatory diseases simultaneously. We designed, synthesized, and characterized a Gd complex of 1,4,7-tris(carboxymethylaza) cyclododecane-10-azaacetylamide (DO3A) conjugated with a nonsteroidal anti-inflammatory drug (NSAID) that exerts the innate therapeutic effect of NSAIDs and is also applicable in MRI diagnostics. Gd-DO3A-fen (0.1 mmol/kg) was intravenously injected into the turpentine oil-induced mouse model, with Gd-DO3A-BT as a control group. In the in vivo MRI experiment, the contrast-to-noise ratio (CNR) was higher and persisted longer than that with Gd-DO3A-BT; specifically, the CNR difference was almost five times at 2 h after injection. Gd-DO3A-fen had a binding affinity (Ka) of 6.68 × 106 M-1 for the COX-2 enzyme, which was 2.1-fold higher than that of fenbufen, the original NSAID. In vivo evaluation of anti-inflammatory activity was performed in two animal models. In the turpentine oil-induced model, the mRNA expression levels of inflammatory parameters such as COX-2, TNF-α, IL-1β, and IL-6 were reduced, and in the carrageenan-induced edema model, swelling was suppressed by 72% and there was a 2.88-fold inhibition compared with the saline group. Correlation analysis between in vitro, in silico, and in vivo studies revealed that Gd-DO3A-fen acts as an anti-inflammatory theragnostic agent by directly binding to COX-2.

Meliasendanins E-J, Nor-neolignan Constituents from Melia toosendan and their Anti-inflammatory Activity

A phytochemical investigation of the fruits extract of Melia toosendan afforded the isolation of two new nor-neolignans, meliasendanins E (1) and F (2), as well as twelve known compounds (3 - 14) using various separation technique such as Diaion HP20, silica, RP-18 gel column chromatography and semi-preparative HPLC. Their chemical structures were elucidated by extensive NMR spectroscopic data including 2D-NMR, and HR-ESI-MS as well as ECD data. Among the twelve known compounds, the absolute structures of 3 - 6 were determined first, and given the trivial names as meliasendanins G-J (3 - 6). Based on the evaluation of anti-inflammatory activity, compounds 7 - 8 exhibited inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 34.6 and 39.5 μM, respectively.

Evaluation of anti-inflammatory, diuretic and oral glucose tolerance activities of phenolic compound-rich fractions of Hammada articulata in Albino Wistar rats

Hammada articulata is a plant widely used by the locals of the Algerian Sahara for multiple medicinal purposes. However, little was known about its chemical composition and the mechanisms of its bioactivity. For this purpose, the derived extracts [chloroform (CHCl3), ethyl acetate (EtOAc) and n-butanol (n-BuOH)] of the 80% ethanol extract of its aerial parts, were evaluated for their anti-inflammatory, diuretic, and anti-hyperglycemic activities in vivo. A preliminary phytochemical screening of H. articulata extracts showed the presence of a variety of secondary metabolites. RP-HPLC/DAD was used to analyze some fractions obtained by fractionation of the three derived extracts, by column chromatography and chosen because of the abundance and simplicity of their chemical composition. The fractions obtained from EtOAc and n-BuOH extracts showed a particular richness in phenolic compounds mainly naringenin, quercetin, kaempferol, myricetin, and rutin, which were known for their many interesting biological activities. The three derived extracts from H. articulata were assessed for their anti-inflammatory activity in the carrageenan-induced edema model in rats and their diuretic activity using hydrochlorothiazide (HCTZ) as a diuretic reference. All extracts showed considerable anti-inflammatory activity; the highest was registered in the group treated with the n-BuOH extract. However, for the diuretic activity, only the chloroform extract was active, with a diuretic spectrum similar to that of the standard diuretic HCTZ. The anti-hyperglycemic effect was carried out on the three derived extracts administered orally at a dose of 200 mg/kg, using the glucose tolerance test after gavage with the extracts. The EtOAc and n-BuOH extracts showed significant anti-hyperglycemic activity, improving oral glucose tolerance in normal rats.

Anti-Inflammatory Activity Evaluation of the Extract and Topical Pre-Formulation of Morus nigra Fruits

Natural products are often a source for bioactive compounds which have great potential for developing novel therapeutic agents. In this sense, the present study aimed to formulate and evaluate a gel containing Morus nigra leaf extract and to evaluate its anti-inflammatory (in-vivo) and antioxidant (in-vitro) activity. The anti-inflammatory activity was evaluated using Carrageenan-induced paw oedema. The antioxidant activity is evaluated by the lipid peroxidation inhibition and DPPH radical scavenging method. The results indicated that the extract (oral and topical route) and the blackberry gel (topical route) produced a significant anti-inflammatory activity (p < 0.05) compared to the untreated control, and similar to the reference drugs (ibuprofen and diclofenac). Regarding antioxidant activity, the Morus nigra extract also showed a significant activity in the tested models. Based on the above observations and results, mora gel formulation was found to be a promising anti-inflammatory formulation and further extensive in-vitro and in-vivo studies are warranted to evaluate its safety and biological potency and which may be useful for further clinical applications.

Interactions of N-Mannich Bases of Pyrrolo[3,4-c]pyrrole with Artificial Models of Cell Membranes and Plasma Proteins, Evaluation of Anti-Inflammatory and Antioxidant Activity.

Despite the widespread and easy access to NSAIDs, effective and safe treatment of various inflammatory disorders is still a serious challenge because of the severe adverse effects distinctive to these drugs. The Mannich base derivatives of pyrrolo[3,4-c]pyrrole are potent, preferential COX-2 inhibitors with a COX-2/COX-1 inhibitory ratio better than meloxicam. Therefore, we chose the six most promising molecules and subjected them to further in-depth research. The current study presents the extensive biological, spectroscopic and in silico evaluation of the activity and physicochemical properties of pyrrolo[3,4-c]pyrrole derivatives. Aware of the advantages of dual COX-LOX inhibition, we investigated the 15-LOX inhibitory activity of these molecules. We also examined their antioxidant effect in several in vitro experiments in a protection and regeneration model. Furthermore, we defined how studied compounds interact with artificial models of cell membranes, which is extremely important for drugs administered orally with an intracellular target. The interactions and binding mode of the derivatives with the most abundant plasma proteins-human serum albumin and alpha-1-acid glycoprotein-are also described. Finally, we used computational techniques to evaluate their pharmacokinetic properties. According to the obtained results, we can state that pyrrolo[3,4-c]pyrrole derivatives are promising anti-inflammatory and antioxidant agents with potentially good membrane permeability.

Synthesis and in silico studies of some new pyrrolidine derivatives and their biological evaluation for analgesic and anti-inflammatory activity

An array of commercially viable intermediate molecules necessary for the synthesis of a variety of bioactive molecules are chemically synthesized by pyrrolidine and its derivatives, which play a significant role in drug design and development process. The aim of the present research work was to explore the synthesis of some new pyrrolidine derivatives and to perform their in silico studies and finally evaluation of analgesic and anti-inflammatory activity. The purpose of this study was to synthesis new pyrrolidine derivatives, examine how they affected the COX-1 and COX-2 enzymes computationally, and to screen their in vivo analgesic and anti-inflammatory activity on laboratory animals. The new pyrrolidine derivatives were synthesized by condensing N-(3-acetylphenyl)-2-(pyrrolidin-1-yl)acetamide with substituted aniline in ethanol in the presence of catalytic amounts of glacial acetic acid. The structures of novel pyrrolidine derivatives were characterised using IR, NMR, and mass spectroscopy. Several molecular properties of the newly synthesized derivatives were calculated in order to evaluate the nature of the drug-like candidate. A specific reference cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme was used to dock the newly synthesized pyrrolidine derivatives. From the observed data, it was noted that amongst all newly synthesized compounds, A-1 and A-4 exhibited the highest anti-inflammatory and analgesic effects, respectively. On the basis of findings of present research, it was concluded that A-1 and A-4 might be utilized as a promising new lead compound for Non-Steroidal Anti-Inflammatory Drug (NSAIDs) development.

Phytochemicals and Biological Activities of Pulicaria genus: Emphasis on the Flavonoids and Sesquiterpenoids and Cytotoxicity Effects

Abstract: The use of herbal remedies is more current in illnesses with chronic diseases. One of these important applications is the usage of many plant-derived compounds as cytotoxic agents for the treatment of cancers. Various research has been done on several species of Pulicaria genus for the evaluation of antihistaminic, antimicrobial, antitumor, antiinflammatory, antioxidant, antibacterial, antifungal, insecticide, and leishmanicidal activities. Some studies have shown that these plants have a rich pool of biometabolites like diterpenes, sesquiterpenes, caryophyllenes, flavonoids, and sesquiterpenoids. The main components in several species of this genus are flavonoids and sesquiterpenoids, which have been identified in chemotaxonomic studies and have shown cytotoxic properties. The Scopus and Science Direct sites were studied to find articles on flavonoid and sesquiterpenoid compounds that have been isolated from the Pulicaria genus. : Several biological compounds were isolated from different species of the Pulicaria genus. The main compounds are flavonoids and sesquiterpenoids, which have different biological effects. Its main effect is cytotoxic effect against several cancer cell lines. This study indicates that the Pulicaria genus has cytotoxic activity but posterity studies are needed to probe the active compounds and their possible expansion as novel anticancer drugs.

Polyphenols with Anti-Inflammatory Properties: Synthesis and Biological Activity of Novel Curcumin Derivatives.

Herein, we describe the synthesis and evaluation of anti-inflammatory activities of new curcumin derivatives. The thirteen curcumin derivatives were synthesized by Steglich esterification on one or both of the phenolic rings of curcumin with the aim of providing improved anti-inflammatory activity. Monofunctionalized compounds showed better bioactivity than the difunctionalized derivatives in terms of inhibiting IL-6 production, and known compound 2 presented the highest activity. Additionally, this compound showed strong activity against PGE2. Structure-activity relationship studies were carried out for both IL-6 and PGE2, and it was found that the activity of this series of compounds increases when a free hydroxyl group or aromatic ligands are present on the curcumin ring and a linker moiety is absent. Compound 2 remained the highest activity in modulating IL-6 production and showed strong activity against PGE2 synthesis.

A novel CDK8 inhibitor with poly-substituted pyridine core: Discovery and anti-inflammatory activity evaluation in vivo

As an ideal anti-inflammatory target, cyclin-dependent kinase 8 (CDK8) has gradually attracted the attention of researchers. CDK8 inhibition up-regulates Interleukin-10 (IL-10) expression by enhancing the transcriptional activity of activator protein-1 (AP-1), and augmenting IL-10 abundance is a viable strategy for the treatment of inflammatory bowel disease (IBD). In this research, through structure-based drug design and dominant fragment hybridization, a series of poly-substituted pyridine derivatives were designed and synthesized as CDK8 inhibitors. Ultimately, compound CR16 was identified as the best one, which exhibited good inhibitory activity against CDK8 (IC50 = 74.4 nM). In vitro and in vivo studies indicated that CR16 could enhance the transcriptional activity of AP-1, augment the abundance of IL-10, and affect CDK8-related signaling pathways including TLR7/NF-κB/MAPK and IL-10-JAK1-STAT3 pathways. In addition, CR16 showed potent therapeutic effect in an animal model of IBD.

Design, Synthesis, Molecular docking, and biological evaluation of novel 2,3-diaryl-1,3-thiazolidine-4-one derivatives as potential anti-inflammatory and cytotoxic agents

A new series of 2,3-diaryl-1,3thiazolidin-4-one derivatives was designed, synthesized, and evaluated for their cytotoxicity and COXs inhibitory activities. Among these derivatives, compounds 4 k and 4j exhibited the highest inhibitory activities against COX-2 at IC50 values of 0.05 and 0.06 μM, respectively. Compounds 4a, 4b, 4e, 4 g, 4j, 4 k, 5b, and 6b, which exhibited the highest inhibition% against COX-2, were evaluated for their anti-inflammatory activity in rats. Results showed 41.08–82.00 % inhibition of paw edema thickness by the test compounds compared to celecoxib (inhibition% = 89.51 %). In addition, compounds 4b, 4j, 4 k, and 6b exhibited better GIT safety profiles compared to celecoxib and indomethacin. The four compounds were also evaluated for their antioxidant activity. The results revealed the highest antioxidant activity for 4j (IC50 = 45.27 μM) comparable to torolox (IC50 = 62.03 μM). The antiproliferative activity of the new compounds was evaluated against HePG-2, HCT-116, MCF-7, and PC-3 cancer cell lines. The results showed the highest cytotoxicity for compounds 4b, 4j, 4 k, and 6b (IC50 = 2.31–27.19 μM), with 4j being the most potent. Mechanistic studies revealed the ability of 4j and 4 k by inducing marked apoptosis and cell cycle arrest at the G1 phase in HePG-2 cancer cells. These biological results may also suggest a role for COX-2 inhibition in the antiproliferative activity of these compounds. The results of the molecular docking study for 4 k and 4j into the active site of COX-2 revealed good fitting and correlation with the results of the in vitro COX‑2 inhibition assay.

Synthesis and characterization techniques for clay-based polymer nanocomposites and their evaluation of antibacterial, anticancer, and anti-inflammatory activities

Synthesis and characterization techniques for clay-based polymer nanocomposites and their evaluation of antibacterial, anticancer, and anti-inflammatory activities

Evaluation of Wound Healing and Anti-Inflammatory Activities of 80% Methanol Crude Extract and Solvent Fractions of Trichilia dregeana Sond (Meliaceae) Leaves in Mice.

The leaves of Trichilia dregeana Sond are traditionally used to treat wounds. Even though there have been in vitro studies and claims supporting wound healing, there are no scientific data on in vivo wound healing and anti-inflammatory activities of the leaves of T. dregeana. This study aimed to evaluate wound healing and anti-inflammatory activity of 80% methanol crude extract and solvent fractions of T. dregeana in mice. The leaves of T. dregeana were dried, ground, and macerated with 80% methanol three times successively. The crude extract was fractioned by water, ethyl acetate, and hexane separately. The acute dermal and oral toxicity tests were done by applying 2000 mg/kg of 10% (w/w) crude extract ointment (CEO) topically and 2000 mg/kg of crude extract orally, respectively. The wound healing activity of the crude extract was evaluated on excision, incision, and burn wound models while the fractions were evaluated only on excision wound model. The anti-inflammatory activity of the crude extract was evaluated on xylene-induced ear edema and cotton pellet granuloma tests. Both acute dermal and oral toxicity tests were found to be safe after topical application of 2000 mg/kg of 10% (w/w) CEO and oral administration of 2000 mg/kg of crude extract suspension, respectively. Both 5% and 10% (w/w) CEO produced significant (p < 0.001) wound contraction and period of epithelialization from day 4 onwards as compared to simple ointment (SO) on both excision and burn wounds. The tensile strength was increased significantly (p < 0.001) for the CEO-treated mice as compared to both untreated and SO groups. The crude extract also showed anti-inflammatory activity at 100, 200, and 400 mg/kg by inhibiting ear edema, exudate, and granuloma formation as compared to the SO group. The increase in wound contraction, reduction in period of epithelialization, and increase in tensile strength support the traditional claims of T. dregeana for wound healing.

Pharmacological evaluation of analgesic, anti-pyretic and anti-inflammatory activities of ethanolic root extract of Amaranthus caudatus

Background: Amaranthus caudatus Linn, belonging to a family Amaranthaceae. Amaranthus caudatus is found in South America, India, or Indo-Chinese district, Mexico, and the Mediterranean area. Amaranthus caudatus contains different kinds of substance constituents which are responsible for its therapeutic potential. Amaranthus caudatus is usually utilized in the treatment of jaundice, amoebiasis, and kidney ailment, as a blood purifier, diuretic, abortifacient, vermifuge, astringents, and for liver illness. The research work deals with the screening of the analgesic, antipyretic and anti-inflammatory activities of ethanolic root extract of Amaranthus caudatus. For this, the alcoholic extract of the selected plant was used for analgesic activity, anti-inflammatory activity and anti-pyretic activities.&#x0D; The result: In current investigation, diclofenac sodium (10mg/kg, p.o.) was used as a standard drug. The effects of ethanolic root extract (200 and 400mg/kg, p.o.) of Amaranthus caudatus on Wistar albino rats for the assessment of analgesic, anti-inflammatory as well as antipyretic activities. The current research revealed that EEAC (200 and 400mg/kg,p.o.) possessed significant (P&lt;0.05) analgesic, anti-inflammatory and antipyretics activities in a dose-dependent manner. Furthermore EEAC (200 and 400mg/kg p.o) were effective as standard drug (Diclofenac sodium 10mg/kg, p.o). All these methods were performed under highly supervised conditions and by proper handling of experimental animals having been granted permission by IAEC.&#x0D; The conclusion: In the present study, it was concluded that the EEAC was effective in a dose-dependent manner and possessed potent analgesic, anti-inflammatory and antipyretic activities.&#x0D; Keywords: Amaranthus caudatus, Analgesic, Anti-pyretic, Anti-inflammatory, Diclofenac sodium, Phytochemical screening.

Synthesis, biological evaluation and molecular docking study of some new 4-aminosalicylic acid derivatives as anti-inflammatory and antimycobacterial agents

In this study, new derivatives of the antitubercular and anti-inflammatory drug, 4-aminosaliclic acids (4-ASA) were synthesized, characterized, and evaluated for these activities. In vivo and in viro evaluation of anti-inflammatory activity revealed that compounds 10, 19 and 20 are the most active with potent cyclooxygenase-2 (COX-2) and 5-lipooxgenase (5-LOX) inhibition and without causing gasric lesions. The minimum inhibitory concentrations (MIC) of the newly synthesized compound were, also, measured against Mycobacterium tuberculosis H37RV. Among the tested compounds 17, 19 and 20 exhibited significant activities against the growth of M. tuberculosis. 20 is the most potent with (MIC 1.04 µM) 2.5 folds more potent than the parent drug 4-ASA. 20 displayed low cytotoxicity against normal cell providing a high therapeutic index. Important structure features were analyzed by docking and structure–activity relationship analysis to give better insights into the structural determinants for predicting the anti-inflammatory and anti-TB activities. Our results indicated that compounds 19 and 20 are potential lead compounds for the discovery of dual anti-inflammatory and anti-TB drug candidates.

Experimental evaluation of analgesics and anti-inflammatory activity of Punarnavadi Guggulu and Panchavalkaladi Taila

Experimental evaluation of analgesics and anti-inflammatory activity of Punarnavadi Guggulu and Panchavalkaladi Taila

Evaluation of Analgesic and Anti-inflammatory Activities of Methanolic Leaf and Root Extracts of Gomphocarpus purpurascens A. Rich (Asclepiadaceae) in Mice.

Regardless of the availability of drugs many people still experienced pain and inflammation because current medications often trigger potentially serious adverse effects. A range of medicinal plants with analgesic and anti-inflammatory properties have been widely used by traditional healers. Among them, Gomphocarpus purpurascens is one however there are no experimental studies that support this traditional use. This study aimed to evaluate the analgesic and anti-inflammatory activities of 80% methanolic leaf and root extracts of G. purpurascens. Air-dried leaves and roots of G. purpurascens were extracted with 80% methanol and an acute oral toxicity study was conducted for the 80% methanolic extract of G. purpurascens according to OECD guideline version eighteen. Preliminary phytochemical screening for the presence of different constituents was carried out. The hot plate method was used to evaluate centrally mediated analgesic activity while peripheral analgesic activity was tested by an acetic acid-induced writhing test. Carrageenan-induced paw edema test and formalin-induced pedal edema test were used to evaluate anti-inflammatory activity. Dose-dependent inhibition of acetic acid-induced writhing test was observed in mice by 100 mg/kg, 200 mg/kg, and 400 mg/kg of root extract with respective values of 16.6%, 68.9%, and 83%. In the hot plate method, the root extract at doses of 200mg/kg and 400 mg/kg showed a significant (p < 0.05) analgesic effect. Maximum anti-inflammatory effects by all doses of leaf extracts were observed from 2-4hr post-induction in carrageenan-induced paw edema; and all tested doses of the extract inhibited the formalin-induced inflammation significantly (p < 0.001, p < 0.01). The presence of saponins, alkaloids, flavonoids, tannins, terpenoids, anthraquinone, steroids, and phenols might be responsible for these activities. This study shows that the extract had potential analgesic and anti-inflammatory activity which supports the traditional claim.

Phytochemical investigation and pharmacological evaluation of Anti-inflammatory activity of Vitex negundo linn bark extracts

Asthma is a disease characterized by acute exacerbation of coughing dysponea, wheezing and chest tightness. Patients usually have reduced forced expiration volume in one sec as well as reduced airflow The current study aimed to evaluate the phytochemical investigation and pharmacological evaluation of anti-inflammatory activity of Vitex negundo linn bark extracts. The results when compared with 0 Hr reading of same group at specific dose levels tested (200 mg/kg, 400mg/kg and 600 mg/kg), it was observed that methanolic extract of Vitex negundo linn bark started showing the protection after 2 hrs at 200 mg/kg and 600mg/kg whereas 400 mg/kg showed at the end of 1 hr itself and continued till the end of 5 hrs and quite comparable with that of Ibuprofen. These results are encouraging enough to pursue bioactivity-guided fractionation of this extract and structure elucidation of the active phyto constituents.

In vitro evaluation of anti-inflammatory activity of cornsilk and clove in combination

In vitro evaluation of anti-inflammatory activity of cornsilk and clove in combination