Management Of Inflammatory Conditions Research Articles

Therapeutic potential of Leea asiatica: Chemical isolation and validation of ethnomedicinal claims through in vitro and in silico assessment of antioxidant and anti-inflammatory properties

Leea asiatica (L.) Ridsdale has been used by different ethnic communities to manage diseased conditions that can be traced to oxidative stress and cellular inflammations but scientific evidences to support the claim are scanty. The objective of this study was to isolate and identify the antioxidants present in the aerial parts of Leea asiatica, perform their molecular docking against proteins to inspect whether the traditional uses of the plant can be validated by an in-silico approach. Quercetin (1), gallic acid (2), kaempferol (3), methyl gallate (4), myricetin 3-O-α-L-rhamnopyranoside (5), (−)-epicatechin-3-O-gallate (6) and (−)-epigallocatechin-3-O-gallate (7) were isolated from the 70 % methanolic extract of the aerial parts. Compounds 2, 4, 6, and 7 are reported for the first time from Leea asiatica. Quercetin (1), gallic acid (2), (−)-epicatechin-3-O-gallate (6) and (−)-epigallocatechin-3-O-gallate (7) showed potent antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. Molecular docking with NADPH oxidase and TNF-α revealed that epicatechin-3-O-gallate, epigallocatechin-3-O-gallate and quercetin bound with the least binding energy amongst the isolated compounds as well as standard (Trolox and Prednisolone). By molecular dynamics analysis, epicatechin-3-O-gallate maintained stable conformation with NADPH oxidase and TNF-α and was found to possess good ADMET profile thereby validating the ethnic use of the plant as a medicine in the management of inflammatory conditions by an in vitro and in silico approach.

Resolution Pharmacology: Focus on Pro-Resolving Annexin A1 and Lipid Mediators for Therapeutic Innovation in Inflammation.

Chronic diseases that affect our society are made more complex by comorbidities and are poorly managed by the current pharmacology. While all present inflammatory etiopathogeneses, there is an unmet need for better clinical management of these diseases and their multiple symptoms. We discuss here an innovative approach based on the biology of the resolution of inflammation. Studying endogenous pro-resolving peptide and lipid mediators, how they are formed, and which target they interact with, can offer innovative options through augmenting the expression or function of pro-resolving pathways or mimicking their actions with novel targeted molecules. In all cases, resolution offers innovation for the treatment of the primary cause of a given disease and/or for the management of its comorbidities, ultimately improving patient quality of life. By implementing resolution pharmacology, we harness the whole physiology of inflammation, with the potential to bring a marked change in the management of inflammatory conditions.

Anti-Arthritic Effect of the Hydroethanolic Root Extract of Psydrax subcordata in Rats.

Background In Ghana, decoctions of various parts of Psydrax subcordata, Bridson (Rubiaceae) are employed in the management of inflammatory conditions. However, not much scientific data is available to back such folkloric use of the plant. This study, therefore, seeks to investigate the chronic anti-inflammatory activity of hydroethanolic root extract of Psydrax subcordata (PSRE) using the adjuvant-induced arthritis model in rats. Methods Freund's adjuvant-induced arthritis model was used to assess the ameliorative effects of PSRE in chronic inflammation. The effect of PSRE on tissue and joint integrity in arthritis was also evaluated by histopathology and microscopy. The effect of PSRE on oxidative markers and serum transforming growth factor (TGF) beta 1 was also determined via chemical assays. Results Oral PSRE (30–300 mg/kg) inhibited both ipsilateral and contralateral paw arthritis when given prophylactically and therapeutically in rats. It reduced paw defect on X-ray with histologically-reduced inflammatory cells and synovial hyperplasia. Finally, PSRE significantly reduced TGF-beta 1 levels and raised antioxidants such as reduced glutathione, catalase, and superoxide dismutase levels in arthritic rats. Conclusion The findings show that hydroethanolic root extract of Psydrax subcordata possesses anti-inflammatory properties in rodents.

O04 Large vessel vasculitis related to COVID-19 infection

Case report - IntroductionBy June 2020, 175,000 cases of COVID-19 had been identified in London alone. The most common symptoms include fever, headache, loss of smell, cough, myalgia, and sore throat. The major complication is acute respiratory distress syndrome (ARDS) but systemic complications such as cardiomyopathy, acute kidney injury, encephalopathy and coagulopathy are being identified. A delayed multi-system inflammatory syndrome in children has also been recognised and further complications are likely to be identified as our experience increases. Here, we report the case of a patient with large vessel vasculitis who initially presented with symptoms highly likely to be due to COVID-19 infection.Case report - Case descriptionA 36-year-old black African nurse presented in May 2020, with acute onset 7 days prior of high-grade fevers, rigors, nights sweats, generalised myalgia, sore throat, headache with photophobia, anosmia, dysgeusia and a widespread rash. She was a smoker with no other relevant medical, travel nor sexual history, and no drug use. A COVID-19 swab on day 2 had been negative and she had taken a course of Doxycycline.Examination revealed firm palpable subcutaneous nodules on lower limbs, upper back and forehead and cervical lymphadenopathy. She was photophobic with no meningism. The rest of her physical examination was normal. BP was 116/97 mmHg, heart rate 109 bpm and satO2 100%. Investigations demonstrated C-reactive protein 330mg/L, erythrocyte sedimentation rate 140, Ferritin 479, lymphopaenia 0.7x109, eGFR 54 with no haematoproteinuria, D-dimer 3.05 mg/L with INR 1.1, aPTT 1.3, fibrinogen 8.8 g/L. Hb, WCC, liver function, CK, serum ACE and triglycerides were normal. Infectious screen revealed negative blood cultures, HIV, Hepatitis B and C, EBV, CMV and Treponema pallidum serology. CT brain and CSF analysis were normal including bacterial culture and viral PCR. ANA, ENA, dsDNA, ANCA and aPL antibodies were negative with normal complement levels. Throat swab grew group A streptococcus and she was treated with broad spectrum antibiotics for 7 days maintaining fevers up to 39oC. Skin biopsy was non-specific with negative direct immunofluorescence but showed microvascular thrombi in the papillary dermis. COVID-19 PCR tests (three naso-pharyngeal swabs and one stool PCR) and IgG test (day 38) were negative. CT showed no pneumonitis but non-specific retroperitoneal stranding with medium/large vessel vasculitis involving both proximal renal arteries and a 6 cm segment of mid abdominal aorta on PET-CT. We started oral prednisolone 40mg with immediate resolution of her fevers, myalgia, and inflammatory markers, remaining well a month later.Case report - DiscussionTakayasu’s arteritis is the most common autoimmune large vessel vasculitis (LVV) affecting young females and involves inflammation of the arterial wall ultimately resulting in stenosis and obstruction of the vessel. However, it is rare in patients with African heritage and usually presents with a prolonged prodromal phase. Given the atypical presentation and symptoms consistent with COVID-19 infection we feel that this patients’ LVV may have been a complication of COVID-19 infection. The relationship between infections and vasculitis is complex. TB and syphilis cause aortitis and a relationship between infection and vasculitis has been proven in HBV associated PAN and HCV associated cryoglobulinemia.Experimental data supports a possible association between CMV and herpes virus and Takayasu arteritis. It could, therefore, be hypothesised that COVID-19 infection can trigger LVV. Our patient had a throat swab positive for Streptococcus pyogenes which is an uncommon cause of infective endocarditis and mycotic aneurism, but this patient had no evidence of either endocarditis or aneurism formation and so it was felt the throat swab finding was incidental. Our patient had repeated negative COVID-19 nasopharyngeal swabs and a negative antibody test at day 38.Although this argues against a diagnosis of COVID-19 related illness, the relative lack of information we currently have regarding sensitivities of the tests, at what point COVID-19 PCR becomes negative in the illness and when/if patients develop antibodies, means these negative tests in the presence of typical symptoms cannot exclude the diagnosis. We believe this case is extremely important to highlight a possible novel inflammatory complication of COVID-19 infection. We decided to treat this patient in line with guidance for the management of LVV, including the introduction of methotrexate, but it will be interesting to observe her long-term outcome. Case report - Key learning points Increasing numbers of COVID-19 related systemic inflammatory conditions are likely to be recognised over the coming months. We present the case of patient with large vessel vasculitis who initially presented atypically with symptoms consistent with COVID-19 infectionTo identify these complications, COVID-19 symptoms questioning should be part of any routine medical historyMore information is required regarding the sensitivity of COVID-19 PCR and antibody tests to aid the diagnosis of these conditionsThe long-term management of inflammatory conditions associated with COVID-19 infection is not clear and a discussion is warranted as to whether DMARDs should be initiated

Protective effect of bergapten in acetic acid-induced colitis in rats

Bergapten (5-methoxysporalen) is a furanocoumarin extracted from several species of citrus and bergamot oil. Bergamot essential oil is used traditionally in the management of inflammatory conditions. Previous studies on bergapten have explored mainly its in vitro anti-inflammatory activities which include suppression of the expression and release of pro-inflammatory cytokines such as TNF-α and interleukins as well as prostaglandins. Bergapten enhances the clearance of neutrophils and macrophages from the site of inflammation and reduces oxidative stress by inhibition of reactive oxygen species (ROS). Bergapten was assessed for its anti-inflammatory properties in acetic acid-induced colitis. Animals were obtained and randomly placed in six (6) groups (n = 5) after acclimatization. Colitis was induced by rectal administration using 4% v/v acetic acid in Sprague Dawley rats after pre-treatment for 5 days. Bergapten was administered at doses of 3, 10, and 30 mg kg−1p.o. while the control group received saline 5 mL kg−1p.o. and the standard drug employed was sulphasalazine at a dose of 500 mg kg−1. Assessments made for colon-weight-to-length ratio, colonic injury, and mucosal mast cell degranulation. There were reduced colon-weight-to-length ratios in animals treated with bergapten which was significant (p < 0.5) for doses 10 and 30 mg kg−1 compared to the disease control group Both macroscopic and microscopic damage were reduced as well, with a lesser percentage of degranulated mast cells. Macroscopic damage was reduced for bergapten at doses 10 and 30 mg kg−1 significantly at p < 0.5 and p < 0.001, respectively. Similarly, microscopic damage was reduced at p < 0.01 and p < 0.001 respectively for bergapten 10 and 30 mg kg−1. The reduction of degranulation by bergapten was significant at p < 0.001. There was generally reduced damage at inflammatory sites as well as decreased infiltration of inflammatory cells. Overall, bergapten reduces inflammation in acetic acid-induced colitis.

The effect of erdosteine on airway defence mechanisms and inflammatory cytokines in the settings of allergic inflammation

IntroductionMucoactive agent, erdosteine, besides mucolytic activity, is characterized by many other pharmacodynamic properties which could be beneficial in the management of inflammatory conditions. BackgroundUsing guinea pig experimental model of allergic inflammation, we evaluated the ability of erdosteine to modulate airway defence mechanisms and inflammation after 10 days (10 mg/kg/day) administration. MethodsIn vivo changes in specific airway resistance and amplitude of tracheal contraction were estimated to evaluate the bronchodilatory effect. The sensitivity of chemically induced cough reflex was estimated via in vivo method. The ciliary beat frequency assessed on brushed tracheal cells was used as an indicator of the mucociliary clearance rate. The concentrations of the inflammatory cytokines IL-4, IL-5, IL-13 and IL-10 were measured in BALF using multiplex detecting method. ResultsOur data show that 10 days erdosteine administration resulted in bronchodilation and stimulation of ciliary beat frequency. Erdosteine did not affect the parameters of chemically induced cough reflex. Erdosteine demonstrated the modest decline in inflammatory cytokines IL-5, IL-13 and an increase in the concentration of IL-10, which is a potent regulator of inflammatory responses and plays a critical role in controlling allergic airway inflammation. ConclusionIn summary, we can state, that erdosteine is multi-action drug and it seems to have many beneficial and complementary effect in the management of chronic inflammatory airway diseases complicated by viscous mucus.

Outcomes of non-infectious Paediatric uveitis in the era of biologic therapy

BackgroundThere is a paucity of data on the ocular outcomes in paediatric non-infectious uveitis since the introduction of the biologic agents. The purpose of this study was to outline the clinical characteristics of children with non-infectious uveitis and determine the visual outcomes and ocular complication rates in the modern era.MethodsChildren with non-infectious uveitis from January 2011 to December 2015 were identified. Data was collected at baseline, 1, 3, 5, and 10 years post diagnosis. The incidence rates of visual impairment, structural ocular complications and surgical intervention were calculated. Using logistic regression the association between various baseline characteristics and later visual impairment was investigated.ResultsOf the 166 children, 60.2% (n = 100) had a systemic disease association. 72.9% (n = 121) children received methotrexate, 58 children progressed to a biologic. The incidence rates of visual acuity loss to > 0.3 LogMAR (6/12) and to ≥1.0 LogMAR (6/60) were 0.05/Eye Year (EY) and 0.01/EY, respectively. Visual outcomes in the Juvenile Idiopathic Arthritis associated Uveitis (JIA-U) and Idiopathic Uveitis cohorts were not statistically significant. Of the 293 affected eyes, posterior synechiae was the predominant complication on presentation, while cataract had the highest incidence rate (0.05/EY). On direct comparison, children with JIA-U were statistically significantly more likely to develop glaucoma while children with Idiopathic Uveitis were statistically significantly more likely to develop macular oedema.ConclusionOne third of children received a biological therapy, reflecting increasing utilisation and importance of biological agents in the management of inflammatory conditions. Rates of visual impairment and ocular complications are an improvement on previously published data.

BIOACTIVE CONSTITUENTS RESPONSIBLE FOR THE ANTI-INFLAMMATORY ACTIONS OF JATROPHA CURCAS

Inflammatory disorders are linked to the pathogenesis of several diseases. Limitations posed by synthetic anti-inflammatory agents had inspired the need to source for more effective and safer natural alternatives. This study evaluated the anti-inflammatory activities of the twig extracts and fractions of Jatropha Curcas (J. curcas) and also identify the phytocompounds responsible for its anti-inflammatory activities. The methanol/methylchloride extract of J. curcas twig was fractionated into n-hexane, ethyl acetate and butanol fractions. The effects of extracts and fractions of J. curcas twig on xylene induced topical inflammation were evaluated. HPLC and LC-MS of the promising fraction was evaluated. Results showed that the extract exhibited high anti-inflammatory activity at 500 µg/ear (66%) and 250 µg/ear (51%) compared to the positive control, piroxicam with 45% inhibition at 250 µg/ear. Ethyl acetate fraction significantly (p&lt;0.05) suppressed the development of xylene ear edema compared to Piroxicam. HPLC of the fractions revealed the anti-inflammatory phytocompounds; pinoresinol, orientine, quercetin, septicin and naamin F. LC-MS analysis mass spectra showed mass peaks [M-H]-of m/z 299.4, 599.1 and [M+H]+m/z 301 which represents a mass of 300 of an unknown compound. These findings suggest that the twigs of J. curcas possess promising anti-inflammatory phytocompounds which justify its use in the management of inflammatory conditions in traditional medicines.

FORMULATION &amp; CHARACTERIZATION OF NANOSTRUCTURED LIPID CARRIER (NLC) BASED GEL FOR TOPICAL DELIVERY OF ETORICOXIB

Nanostructured lipid carriers (NLC)-based topical gel of Etoricoxib was prepared with the aim for the treatment of inflammation and allied conditions. The composition of NLC consisted of Stearic acid as solid lipid, oleic acid as liquid lipid and tween 80 as a surfactant. NLCs prepared by melt-emulsification and low temperature solidification techniques were characterized by particle sizing technology, scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). All of the NLC showed high entrapment efficiency ranging from 69% to 76%. Both the entrapment and release rate were affected by the percentage of oleic acid. NLC-F3G-C was selected as best formulation with average particle size of 244 nm and polydispersity index of 0.690 indicating homogeneity in particle size distribution. The higher magnitude of zeta potential of NLC-F3G-C indicates the stability of formulation. The nanoparticulate dispersion was suitably gelled and assessed for Physical appearance, Homogeneity, Spreadability and in-vitro permeation study. In-vitro drug release pattern of developed NLC dispersion gel showed burst and prolong release. It was concluded that developed NLC gel of Etoricoxib holds promise for prolonged availability of drug in the skin tissues and can be used for better management of inflammatory conditions. Keywords: Etricoxib • Nanostructured lipid carriers (NLC) • Topical gel • Nanoparticl

&amp;lt;i&amp;gt;Sphaeranthus indicus&amp;lt;/i&amp;gt;: Traditional Wisdom to Modern Medicine—An Orally Active, Potent Cytokine Inhibitor for the Management of Inflammatory Disorders

Tumor necrosis factor (TNF-α) is a key regulator of the inflammatory and tissue destruc-tive pathways in rheumatoid arthritis (RA). The clinical success of anti-TNF-α and an-ti-IL-17 biologics has validated the concept that cytokine blockade is beneficial in RA. However, as these drugs are parenterally administered, our efforts are directed at identifying a novel orally active TNF-α inhibitor with a therapeutic profile similar to that of biologics. Since plants are natural immunomodulators, we explored the immunomodulatory potential of Sphaeranthus indicus extract. In our studies, the extract dose-dependently inhibited the release of cytokines in stimulated human peripheral blood mononuclear cells (hPBMCs), and their spontaneous release in synovial cells derived from patients suffering from RA. TNF-α and IFN-γ induced release of p40 subunit of IL-12/ IL-23, and p19 subunit of IL-23 in differentiated THP-1 cells is potently blocked. The expression of endothelial cell adhesion molecules in TNF-α-stimulated HUVECs was also potently inhibited. The oral treatment significantly and dose-dependently reduced LPS-induced TNF-α and IL-1β production in mice. Disease regression was seen in collagen-induced arthritis in DBA/1J mice, which was validated along with radiological and histopathological evaluation. Therefore, the extract of Sphaeranthus indicus could be used in the management of inflammatory conditions.

Erythrocyte n-3pufa levels predict inflammatory status in older australians

Erythrocyte n-3pufa levels predict inflammatory status in older australians

Anti-inflammatory, antioxidant and in silico studies of Buddleja salviifolia (L). Lam leaf constituents

Buddleja salviifolia leaves are used for the treatment of eye infections and neurodegenerative conditions in South Africa. Three phenolic compounds identified as 4′-hydroxyphenyl ethyl vanillate (1), acteoside (2) and quercetin (3) from leaf extracts of the B. salviifolia were investigated for cyclooxygenase-2 (COX-2) inhibition and antioxidant activities using β-carotene–linoleic acid and DPPH assays. In silico parameters were also determined for COX-2. All the compounds exhibited good inhibition activity against COX-2 and moderate antioxidant activities at a screening concentration of 25.0μg/ml. Acteoside was the most potent in all assays. It exhibited the lowest IC50 value (4.28μg/ml) in the COX-2 and EC50 values of 24.15 and 63.30μg/ml in the β-carotene–linoleic acid and DPPH assays respectively. Computational molecular docking showed its molecular interaction with important amino acid residues in the catalytic site of COX-2, revealing its potential binding mode at the molecular level. In silico study revealed that quercetin and acteoside showed the highest binding affinity (dock score of 92.18 and 68.93k.cal/mol) and good hydrogen bond interactions with active site residues. The activities demonstrated by these compounds (1–3) suggest that they could be useful in management of inflammatory conditions.

Isolation and Characterization of Antioxidative Constituents of Ceiba Pentandra (Kapok) Leaves Extract

Ceiba pentandra widely employed in the management of inflammatory conditions, infections and oxidative stress related diseases was investigated for its active constituents. A DPPH-directed fractionation of the ethyl acetate solvent fraction of a 20% aqueous methanol leaves extract of Ceiba pentandra afforded a clovamide derivative, N-trans-caffeoyl-DOPA-methyl ester (1) together with a flavonoid, acacetin-7-O-rutinoside, Linarin (2) and 3,4- dihydroxybenzoic acid, protocatechuic acid (3). Structure elucidation of the isolated compounds was carried out using spectroscopic techniques: mass spectrometry (ESI-TOF-MS), 1D NMR ( 1 H, 13 C and DEPT) as well as 2D experiments (GCOSY, GHSQC and GHMBC). In the qualitative antioxidant assay, compounds 1- 3 bleached the DPPH purple colour indicating free radical scavenging potential (antioxidant activity). Isolation of these antioxidant compounds could provide rationale for the use of this plant in traditional medicine in the management of the oxidative stress related diseases and infections. Keywords : Ceiba Pentandra , Bombacaceae, Clovamide, Antioxidant

Analgesic and Anti-inflammatory Activities of the Fruit Extract of Ampelocissus latifolia (Roxb) on Laboratory Animals

Aim of Study: This study was aimed to evaluate the possible analgesic and anti-inflammatory properties of the ethanol extract of fruit of Ampelocissus latifolia (Roxb).Study Design: Assessment of analgesic and anti-inflammatory activities.Place and Duration of Study: Department of Pharmacy, North South University, Dhaka, Bangladesh, between June 2012 and March 2013.Methodology: The crude ethanol extract was investigated for the anti-inflammatory effect on Long Evans rats using carrageenan induced rat paw edema method. For anti-inflammatory study, 20 rats were divided into 4 different groups, each receiving either distilled water, standard drug or the extract at the doses of 250 and 500mg/kg body weight (BW). The analgesic activity was evaluated by hot plate and acetic acid induced writhing method in Swiss albino mice divided into 4 different groups (control, standard and extract at two different doses of 250 and 500 mg/kg BW).Results: The results of preliminary phytochemical study revealed the presence of alkaloids, flavonoids, tannins, glycosides in significant amounts. The results of anti inflammatory activity study showed that the fruit extracts at a dose of 250 mg/kg and 500 mg/kg inhibited carrageenan-induced paw edema in Long- Evans rats. Both the extracts were able to show a dose dependent anti-inflammatory activity as compared to diclofenac sodium used as a standard drug. The extract elicited a highly significant (p<0.001) analgesic activity in a dose dependent manner on hot plate method, acetic acid-induced writhing test. In the hot plate method, the extract increased the reaction time of heat sensation to 94.71% and 82.7% at the doses of 250 and 500 mg/kg BW while that of the standard drug was 61.45% at the 3rd hour of study. In acetic acid induced writhing test, the percent inhibition of writhing response by the extract was 50.57% and 59.77% at 250 and 500 mg/kg doses respectively (p<0.001).Conclusion: The anti-inflammatory and analgesic effect of the ethanol fruit extract of Ampelocissus latifolia (Roxb) may be due to the presence of various chemical constituents especially flavonoids, tannins, alkaloids or terpenoids. These experimental findings would further establish the scientific basis of the traditional uses of the plant in the management of inflammatory conditions as well as control of pain.

Acetylcholinesterase Inhibitors from Croton sylvaticus Ethyl Acetate Leaf Extract and their Mutagenic Effects

Croton sylvaticus is a medicinal plant widely employed in the management of inflammatory conditions, infections and oxidative stress related diseases such as insomnia, abdominal and internal inflammations. The activities demonstrated by the plant extracts support that its constituents possess the ability to reduce oxidative damage to body cells. Repeated column fractionation of the ethyl acetate fraction of a 20% aqueous methanol leaf extract using acetylcholinesterase (AChE) activity directed on Sephadex LH-20 afforded three compounds identified by mass spectrometry, and 1D and 2D NMR spectroscopy as: 2′-(3″,4″-dihydroxyphenyl)-ethyl-4-hydroxybenzoate (1), 3, 3′, 4′, 5, 7-pentahydroxyflavone (quercetin) (2), and 3, 4′, 5, 7-tetrahydroxyflavone (kaempferol) (3). These compounds are reported from the leaf extracts of C. sylvaticus for the first time and compound 1 is a new natural product. The microplate technique was used to determine the inhibitory effects of the plant extracts (crude and solvent fractions) and isolated compounds against AChE. The IC50 values of the compounds ranged from 60.7 to 415.0 μg/mL, with compound 2 having the best inhibitory activity; the IC50 values of the plant crude extract and solvent fractions ranged from 235.0 to 4695.0 μg/mL. The ethyl acetate fraction had the best inhibitory activity (IC50=235.0 μg/mL). The three compounds showed no mutagenic effects against Salmonella typhimurium tester strains TA98 and TA100. The activity demonstrated by these compounds suggests that they could be effective in the management of neurodegenerative disorders.

Molecular docking of taraxerol acetate as a new COX inhibitor

Cycloxygenase inhibitors are one of the main class of therapeutic agents for management of inflammation. New COX inhibitors are discovered from natural and synthetic sources. In the current investigation taraxerol acetate have been discovered as a new COX inhibitor. Taraxerol acetate showed considerable inhibitory activity against both COX-1 (IC50: 116.3 ± 0.03 ?M) and COX-2 (IC50: 94.7 ± 0.02 ?M) enzymes using in-vitro enzyme inhibition assay. Molecular docking revealed significant interactions of taraxerol acetate with the important amino acid residues surrounding the inhibitor in binding pocket of COX-2 enzyme. This study indicate potential of taraxerol acetate to be further explored and modified as a new lead compound for better management of inflammatory conditions via targeting COX enzymes.

Acetylcholinesterase inhibitory activity and mutagenic effects of Croton penduliflorus leaf extract constituents

Croton penduliflorus is a medicinal plant widely employed in the management of inflammatory conditions, infections and oxidative stress related diseases. The activities demonstrated by leaf extracts indicate that they possess the ability to reduce oxidative damage to cells. Repeated column fractionation of the ethyl acetate fraction of a 20% aqueous methanol leaf extract of C. penduliflorus on Sephadex LH-20 afforded four phenolic compounds: quercetin-3-O-rhamnoside (1), kaempferol-3-O-rhamnoside (2), protocatechualdehyde (3A) and its solvent derived dimer (3B) along with p-hydroxybenzoic acid (4). Compound 3B is described for the first time and its significance in bioassay is briefly outlined. Structure elucidation of the isolated compounds was carried out using spectroscopic techniques. The inhibitory properties of the four compounds against acetylcholinesterase were determined using the microplate assay. The IC50 values of the isolated compounds ranged from 87.9 to 1231.9μM, with compound 2 having the best inhibitory activity (IC50=87.9μM). The four isolated compounds showed no mutagenic effects against Salmonella typhimurium tester strains TA98 and TA100. The moderate activity demonstrated by these compounds suggests that they could be helpful in the management of neurodegenerative disorders.

Development of meloxicam in situ implant formulation by quality by design principle

Objective: The focus of this study was to develop and optimize in situ implant formulation of meloxicam by quality by design (QbD) principle for long-term management of musculoskeletal inflammatory disorders.Methods: The formulation was optimized by Box–Behnken design with polylactide-co-glycolide (PLGA) level (X1), N-methyl pyrrolidone level (X2) and PLGA intrinsic viscosity (X3) as the independent variables and initial burst release of drug (Y1), cumulative release (Y2), and dissolution efficiency (Y3) as the dependent variables. The formulation was physicochemically characterized by scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy and powder X-ray diffraction (PXRD). Pharmacokinetic studies of the optimized formulation were performed on Sprague--Dawley rats.Results: Y1 was significantly affected by X2 and X3. Y2 was affected by X1 and X3 while Y3 was affected by all three independent variables employed in the formulations. Responses for the optimized formulation were in close agreement with the values predicted by the model. SEM photomicrographs indicated uniform gel formulation. No chemical interaction between the components of formulation was observed by FT-IR and meloxicam was found to be present in the amorphous form in the gel matrix as revealed by PXRD. The maximum plasma concentration (Cmax), time to achieve Cmax and area under plasma concentration curve were significantly different from those of the solution formulation used as the control. Plasma concentration of meloxicam was maintained above its IC50 concentration required for COX-2 inhibition for 23 days.Conclusion: Meloxicam in situ implant may provide long-term management of inflammatory conditions with improved patient compliance and better therapeutic index.

Anti-allergic effect of the flavonoid myricitrin from Myrica rubra leaf extracts in vitro and in vivo

Flavonoids are ingested by the general population as anti-oxidant and anti-inflammatory agents. In this study, we investigated the effects of myricitrin, a flavonoid rich in Myrica rubra leaf, upon anti-inflammatory action. Myrica rubra leaf extracts inhibited pro-inflammatory TNFα production in a macrophage cell line, Raw264.7 cells. We observed that the serum IgE levels in the leaf extract-treated DO11.10, a mouse allergy model, were down-regulated. HPLC was performed to demonstrate that M. rubra leaf extracts contain a large amount of myricitrin. We observed an inhibitory effect of HPLC-purified myricitrin on TNFα production in Raw264.7 cells. Thus, myricitrin may be of potential interest in the management of inflammatory conditions.

Antiinflammatory activities of flavonoids and a triterpene caffeate isolated from Bauhinia variegata

In the continuing search for novel antiinflammatory agents, six flavonoids, namely kaempferol (1), ombuin (2), kaempferol 7,4'-dimethyl ether 3-O-beta-D-glucopyranoside (3), kaempferol 3-O-beta-D-glucopyranoside (4), isorhamnetin 3-O-beta-D-glucopyranoside (5) and hesperidin (6), together with one triterpene caffeate, 3beta-trans-(3,4-dihydroxycinnamoyloxy)olean-12-en-28-oic acid (7) were isolated from the non-woody aerial parts of Bauhinia variegata. Compounds 1-7 were evaluated as inhibitors of some macrophage functions involved in the inflammatory process. These seven compounds significantly and dose dependently inhibited lipopolysaccharide (LPS) and interferon (IFN)-gamma induced nitric oxide (NO), and cytokines [tumor necrosis factor (TNF)-alpha and interleukin (IL)-12]. The concentration causing a 50% inhibition (IC50) of NO, TNF-alpha and IL-12 production by compounds 1, 2 and 7 was approximately 30, 50 and 10 microM, respectively, while at 50, 200 and 40 microM compounds 3, 4, and 5, 6 showed 15-30% inhibition, respectively. On the other hand, compounds 3 and 7 showed no inhibitory effect, while compounds 1, 4-6 reduced by around 10-30% the synthesis of NO by macrophages, when inducible NO synthase was already expressed with LPS/IFN-gamma for 24 h. These experimental findings lend pharmacological support to the suggested folkloric uses of the plant B. variegata in the management of inflammatory conditions.