Screening Anti-Inflammatory Effects of Flavanones Solutions.

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

[Modern aspects of inflammatory external ear diseases treatment]. / Sovremennye aspekty lecheniya vospalitel'nykh zabolevanii naruzhnogo ukha.

The article deals with the problem of inflammatory diseases of the external ear. A review of pruritic dermatoses of the external auditory canal was carried out. It has been shown that in chronic dermatoses, the contamination of the skin with bacterial and fungal pathogens significantly increases, which leads to a high risk of developing secondary infectious pathological processes. Treatment of dermatological inflammatory ear diseases includes careful daily hygiene of the external auditory canal and pharmacotherapy, a key aspect of which is the use of topical etiotropic, anti-inflammatory, and symptomatic drugs. The advantage of the combined drug candiderm is described, which, thanks to the unique combination of beclomethasone, gentamicin and clotrimazole in the composition, effectively relieves the symptoms of external ear dermatoses.

Anti-inflammatory effects of Morus alba Linne bark on the activation of toll-like receptors and imiquimod-induced ear edema in mice.

BACKGROUND: Morus alba L. bark has been widely used in traditional medicine for treating several inflammatory diseases, such as hypertension, diabetes mellitus and coughing; however, the molecular mechanisms underlying its anti-inflammatory effects are not well understood. METHODS: We examined the effects of an extract of Morus alba L. bark (MabE) on Toll-like receptor (TLR) ligand-induced activation of RAW264.7 macrophages using a luciferase reporter assay and immunoassays. For the in vivo experiment, we used an imiquimod-induced ear edema model to examine the anti-inflammatory effects of MabE. RESULTS: MabE inhibited the TLR ligand-induced activation of NF-κB in RAW264.7 cells without affecting their viability. Consistent with the inhibition of NF-κB activation, MabE also inhibited the production of IL-6 and IL-1ß from TLR ligand-treated RAW264.7 cells. In vivo MabE treatment inhibited the ear swelling of IMQ-treated mice, in addition to the mRNA expression of IL-17A, IL-1ß and COX-2. The increases in splenic γδT cells in IMQ-treated mice and the production of IL-17A from splenocytes were significantly inhibited by MabE treatment. CONCLUSION: Our study suggests that the anti-inflammatory effects of MabE on the activation of the macrophage cell line RAW246.7 by TLRs and IMQ-induced ear edema are through the inhibition of NF-κB activation and IL-17A-producing γδT cells, respectively.

Volatile Oil of Platycladus Orientalis (L.) Franco Leaves Exerts Strong Anti-inflammatory Effects via Inhibiting the IκB/NF-κB Pathway.

This study was designed to investigate the anti-inflammatory effects of volatile oil of Platycladus orientalis (L.) Franco leaves (VOPF) and the underlying molecular mechanisms by using the non-infectious inflammation rat models and infectious inflammation mouse models. Ear swelling and intraperitoneal capillary permeability in mice, and carrageenan-induced toe swelling and cotton ball-induced granuloma in rats were used to reveal anti-inflammatory effects of VOPF. Moreover, the lipopolysaccharide (LPS)-induced mouse model of acute lung injury was used to explore the anti-inflammatory mechanism of VOPF. The results showed that VOPF could significantly inhibit auricular swelling, intraperitoneal capillary permeability in mice, and reduce granuloma swelling and paw swelling in rats. Furthermore, it significantly alleviated the pathological damage of the lung tissue. In addition, VOPF could reduce the contents of IL-1ß and TNF-α and increase the content of IL-10 in the serum. It had little effect on the expression of p65 but reduced the phosphorylation level of p65 and IκB in NF-κB pathway. In conclusion, VOPF has anti-inflammatory effects and the mechanisms involve the down-regulation of the phosphorylation levels of p65 and IκB and blockage of the NF-κB signaling pathway.

Successful treatment of erythematous-squamous disorders of the external auditory canal with tacrolimus and clotrimazole in otic oil: Our experience in 25 patients.

The external auditory canal (EAC) comprises a special area where erythematous-scaly diseases are located. Among the main dermatoses that can affect EAC seborrheic dermatitis, psoriasis, irritant or allergic contact dermatitis, chronic external otitis (atrial eczematoid dermatitis) and cutaneous lupus should be considered. In this study, 25 consecutive patients were recruited on our dermatological outpatient clinic, 9 men and 16 women, with a clinical diagnosis of localized erythematous-squamous dermatoses in EAC. The mean age was 48.8 years (16-83). The mean time of evolution of the dermatoses was 11.44 months (2-36). Regarding the diagnosis, 14 patients were diagnosed with seborrheic dermatitis (56%), 9 patients with psoriasis (36%), 1 patient with subacute cutaneous lupus (4%), and 1 patient with allergic contact dermatitis to corticosteroids (4%). The indicated treatment was tacrolimus 0.1% and clotrimazole 1% in otic oil, twice a day, for 1 month. The EAC had to be cleaned initially with saline solution impregnated on a swab from the ears. The IGA score and pruritus showed a high results, with important improvement of almost all patients. The satisfaction of the patients obtained with the TSQM-9 questionnaire was 95.2. Retreatment showed an equal efficacy observed during the first treatment period. The efficacy and the absence of side effects with the treatment make this magistral formula an adequate therapeutic option for these dermatoses.

Computational and Biological Comparisons of Plant Steroids as Modulators of Inflammation through Interacting with Glucocorticoid Receptor.

Despite the usefulness of glucocorticoids, they may cause hazardous side effects that limit their use. Searching for compounds that are as equally efficient as glucocorticoids, but with less side effects, the current study compared plant steroids, namely, glycyrrhetinic acid, guggulsterone, boswellic acid, withaferin A, and diosgenin with the classical glucocorticoid, fluticasone. This was approached both in silico using molecular docking against glucocorticoid receptor (GR) and in vivo in two different animal models. All tested compounds interacted with GR, but only boswellic acid and withaferin A showed docking results comparable to fluticasone, as well as similar in vivo anti-inflammatory effects, by significantly decreasing serum levels of interleukin-6 and tumor necrosis factor-α in cotton pellet-induced granuloma in rats. In addition, both compounds significantly decreased the percent of change in ear weight in croton oil-induced ear edema in mice and the granuloma weight in cotton pellet-induced granuloma in rats, to levels comparable to that of fluticasone. Both boswellic acid and withaferin A had no effect on adrenal index, but only withaferin A significantly increased the thymus index. In conclusion, boswellic acid may have comparable anti-inflammatory effects to fluticasone with fewer side effects.

Self-Nanoemulsifying Drug Delivery Systems Containing Plantago lanceolata-An Assessment of Their Antioxidant and Antiinflammatory Effects.

The most important components of Plantago lanceolata L. leaves are catalpol, aucubin, and acteoside (=verbascoside). These bioactive compounds possess different pharmacological effects: anti-inflammatory, antioxidant, antineoplastic, and hepatoprotective. The aim of this study was to protect Plantago lanceolata extract from hydrolysis and to improve its antioxidant effect using self-nano-emulsifying drug delivery systems (SNEDDS). Eight SNEDDS compositions were prepared, and their physical properties, in vitro cytotoxicity, and in vivo AST/ALT values were investigated. MTT cell viability assay was performed on Caco-2 cells. The well-diluted samples (200 to 1000-fold dilutions) proved to be non-cytotoxic. The acute administration of PL-SNEDDS compositions resulted in minor changes in hepatic markers (AST, ALT), except for compositions 4 and 8 due to their high Transcutol contents (80%). The non-toxic compositions showed a significant increase in free radical scavenger activity measured by the DPPH test compared to the blank SNEDDS. An indirect dissolution test was performed, based on the result of the DPPH antioxidant assay; the dissolution profiles of Plantago lancolata extract were statistically different from each SNEDDS. The anti-inflammatory effect of PL-SNEDDS compositions was confirmed by the ear inflammation test. For the complete examination period, all compositions decreased ear edema as compared to the positive (untreated) control. It can be concluded that PL-SNEDDS compositions could be used to deliver active natural compounds in a stable, efficient, and safe manner.

Evaluation of Biological Activity and Computer-Aided Design of New Soft Glucocorticoids.

Soft glucocorticoids are compounds that are biotransformed to inactive and non-toxic metabolites and have fewer side effects than traditional glucocorticoids. A new class of 17ß-carboxamide steroids has been recently introduced by our group. In this study, local anti-inflammatory activity of these derivatives was evaluated by use of the croton oil-induced ear edema test. Glucocorticoids with the highest maximal edema inhibition (MEI) were pointed out, and the systemic side effects of those with the lowest EC50 values were significantly lower in comparison to dexamethasone. A 3D-QSAR model was created and employed for the design of 27 compounds. By use of the sequential combination of ligand-based and structure-based virtual screening, three compounds were selected from the ChEMBL library and used as a starting point for the design of 15 derivatives. Molecular docking analysis of the designed derivatives with the highest predicted MEI and relative glucocorticoid receptor binding affinity (20, 22, 24-1, 25-1, 27, VS7, VS13, and VS14) confirmed the presence of interactions with the glucocorticoid receptor that are important for the activity.

Assesment of the treatment of earlobe keloids with triamcinolone injections, surgical resection, and local pressure.

OBJECTIVE: To evaluate the combined treatment of ear lobe keloids. METHODS: We studied 46 consecutive patients with 81 ear lobe keloids. Patients underwent local infiltration of triamcinolone acetonide (TCN) at concentrations of 40 mg/ml (Group 1), 20 mg/ml (Group 2) and 10mg/ml (Group 3). The volume of TCN infiltrate varied according to the size of the lesion. Treatment consisted of three monthly injections before surgery, excision of keloid in the fourth month and perioperative infiltration, followed by two more leaks TCN within two months. Patients used earrings pressure on the scar after operation for four months. The pressure exerted by earrings in the ear lobe was measured electronically. Post-treatment follow-up of patients was 24 months. RESULTS: TCN at concentrations of 20mg/ml and 40 mg/ml were effective for the treatment of keloids, no difference between the groups (p = 0.58). However, patients in which TCN was infiltrated the 10mg/ml had poor involution of keloid and the study of this group was stopped. CONCLUSION: the combination of infiltration TCN month to 20 mg/mL (1.2mg to 2.0mg per mm3 TCN injury), surgical excision and pressure application device is effective for treatment of keloid ear lobe.

Cecropia pachystachya: a species with expressive in vivo topical anti-inflammatory and in vitro antioxidant effects.

Cecropia pachystachya is a species traditionally used in Brazil to treat inflammation. This work aims to evaluate the topical anti-inflammatory and antioxidant activities of the methanolic extract of C. pachystachya (CPM) and to perform its chemical fingerprint by HPLC-DAD. The topical anti-inflammatory activity was evaluated using the mouse models of acute ear inflammation induced by croton oil, arachidonic acid, capsaicin, EPP, phenol, and chronic inflammation induced by multiple application of croton oil. The in vitro antioxidant effect of CPM was investigated using DPPH, reducing power, ß -carotene bleaching, and TBARS assays. HPLC analysis was performed to quantify the antioxidant phenolics orientin, isoorientin, and chlorogenic acid previously identified in CPM. CPM exhibited significant anti-inflammatory effect in the acute models, in some cases comparable to the reference drugs. Histopathological analysis showed a moderate chronic skin anti-inflammatory effect with decrease in vasodilation, edema, cell infiltration, and epidermal hyperproliferation. It also showed strong in vitro antioxidant activity. The contents of orientin, isoorientin, and chlorogenic acid were 66.5 ± 1.8, 118.8 ± 0.7, and 5.4 ± 0.2 µg/mg extract, respectively. The topical anti-inflammatory activity of CPM could be based on its antioxidant properties, although other effects are probably involved, including COX inhibition and other mechanisms.

New phenylpropanoid and other compounds from Illicium lanceolatum with inhibitory activities against LPS-induced NO production in RAW 264.7 macrophages.

Illicium lanceolatum is a traditional Chinese medicine (TCM) for treating inflammatory diseases. Anti-inflammatory activities of I. lanceolatum stems and leaves were tested using ear edema models induced by dimethyl benzene in mice. Bioassay-guided fractionation of the ethanol extract of I. lanceolatum leaves and stems revealed that the ethyl acetate fraction exhibited inhibitory potency to dimethyl benzene-induced edema in the mouse ear. Phytochemical investigation on the active fraction led to the isolation of a new phenylpropanoid (1), together with fifteen known compounds. This is the first report of the isolation of 2-16 from I. lanceolatum. Of these compounds, compounds 1, 2 and 3 showed inhibitory activity on LPS-stimulated NO production in RAW 264.7 macrophages with IC50 values of 27.58, 26.59 and 34.35 µg/mL, respectively. I. lanceolatum stems and leaves can be exploited to alleviate inflammatory diseases, which makes the rare medicinal plant resources sustainable.

A 10-year review of otic lichen planus: the Mayo Clinic experience.

IMPORTANCE: Lichen planus is an autoimmune inflammatory dermatosis that typically affects the skin but can also involve the stratified squamous epithelium of the external auditory canals and tympanic membranes. Here we report our experience with the clinical presentation, diagnosis, and management of otic lichen planus. OBSERVATIONS: We retrospectively reviewed medical records from January 1, 2001, through May 31, 2011, of patients with a diagnosis of otic lichen planus. Nineteen cases were identified (mean age at diagnosis, 57 years; 15 women). The most common concerns were persistent otorrhea and hearing loss. Other symptoms included plugging, pruritus, tinnitus, pain, and bleeding. The mean symptom duration was 4.0 years (n = 13). Most patients responded well to topical tacrolimus within several months. One patient had a dramatic positive response to rituximab. CONCLUSIONS AND RELEVANCE: Otic lichen planus can lead to persistent hearing loss and should be considered in the differential diagnosis of relentless otorrhea and external auditory canal stenosis. In our experience, topical tacrolimus is the best primary treatment, but alternative therapies could be instituted in severe cases. Early recognition of the nonspecific symptoms of otic lichen planus may lead to prompt treatment and avoidance of irreparable late sequelae.

Nanoporous silica coatings as a drug delivery system for ciprofloxacin: outcome of variable release rates in the infected middle ear of rabbits.

HYPOTHESIS: The present study was performed to examine the impact of the release rate of ciprofloxacin from prostheses coated with nanoporous silica layers on the outcome of an acute bacterial infection of the middle ear of rabbits. BACKGROUND: Middle ear prostheses are often implanted in an infectious environment because of chronic otitis media and cholesteatoma. Bacterial colonization leads to healing disorders after surgery and may lead to the extrusion of the implants. Nanoporous silica layers appear promising as a drug delivery system for antibiotics placed on implants. Before clinical applications can be envisioned, it is necessary to find an optimal release rate. METHODS: White New Zealand rabbits were provided unilaterally with either a "slow release" or a "burst release" ciprofloxacin-containing middle ear Bioverit II prosthesis. After implantation, the middle ears were infected with a solution of Pseudomonas aeruginosa. Afterwards, animals were monitored clinically and, after 3 months, sacrificed to perform necropsy and microbiologic examinations. RESULTS: In the "slow release" group, 7 of 12 animals had to be euthanized preterm because of their poor clinical condition compared with 2 of 12 animals of the "burst release" group (p < 0.05). Clinical and microbiologic examination also showed a better outcome for animals of the burst release group. CONCLUSION: A burst release of ciprofloxacin from middle ear implants is important to combat a perioperative infection with Ps. aeruginosa in the middle ear model of the rabbit.

Anti-inflammatory effect of novel andrographolide derivatives through inhibition of NO and PGE2 production.

Andrographolide (1) is a major diterpene lactone exhibiting anti-inflammatory effects and is found in the plant Andrographis paniculata (Burm. f) Nees, which is widely used in Traditional Chinese Medicine. Synthesis of more effective drugs from andrographolide is very interesting and can prove to be highly useful. In this study, we investigated the anti-inflammatory effects of andrographolide and its derivatives (compounds 2-6) through dimethylbenzene-induced ear edema in mice. Substances under study were administrated intragastrically and the structure-activity relationship was analyzed. Results showed that compounds 5 and 6 significantly inhibited ear edema compared with compound 1 (p<0.05), indicating that the introduction of p-Chlorobenzylidene to C-15 of compound 2 enhances the anti-inflammatory effect. Moreover, compound 6 exhibited the strongest anti-inflammatory effect against ear edema in mice (79.4%; 1.35 mmol/kg, ig) and paw edema in rats (50.4%; 0.90 mmol/kg, ig). In addition, compound 6 significantly (p<0.05) inhibited granuloma formation and reduced the increase in vascular permeability induced by peritoneal injection of 0.6% acetic acid solution in mice. Findings indicate that compound 6 exerts its enhanced anti-inflammatory effects by decreasing serum iNOS activity, NO production, and PGE(2) production.

Treatment of Suqingwan watered pill reduces colon injury induced by experimental colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Sunqingwan watered pill (SWP) is a Chinese medicine compound, traditionally used in the treating UC symptoms like diarrhea, bloody and purulent stool, abdominal pain, etc. The present study aim to examine the effects of SWP on ulcerative colitis using the modern pharmacological models. MATERIALS AND METHODS: To address this question, we used two experimental models of colitis, mice induced by dextran sulfate sodium (DSS) as well as rats induced by 2,4-dinitrochlorobenzene (DNCB). For the mice with DSS-induced colitis, the disease activity index (DAI) and colon histological injuries were observed. For the rat models with DNCB-induced colitis, DAI, levels of nitric oxide (NO) in serum, macroscopic and histological colon injury were investigated. Besides, we also introduced a usually used model of ear swelling induced by xylene in mice to reveal the effect of SWP on acute inflammation. RESULT: In the mice with DSS-induced colitis and the rats with DNCB-induced colitis, SWP could significantly decreased the DAI scores, which meant the body weights of animals were recovered and the gross rectal bleeding reduced. Under the microscope, the histology of colon was obviously changed in SWP administration groups. In the rat models with DNCB-induced colitis, SWP also significantly attenuated macroscopic and colon histological injury. The colon scores in SWP groups in rats was obviously lower than those in the control and similarly the serum levels of NO in the treatment groups were significantly lower than that of control group except for low dosage group of SWP. SWP with the dosages of 1.755 and 3.510 g/kg could inhibit the degree of ear swelling significantly compared with the blank control group (p<0.01), showing it owned good anti-inflammatory activity after 14 days administration. CONCLUSION: SWP is effective on treating UC, especially at the high dose and the mechanism may be related with adjusting the serum level of NO, inhibiting colonic mucosa damage and promoting ulcer repair.

[Effect of intervention of granules of eliminating phlegm and removing blood stasis in cochlear morphology of diabetic rats].

OBJECTIVE: To study the effectiveness of the granules of eliminating phlegm and removing blood stasis (GEPRB) on glucose metabolism for diabetic rats induced by streptozotocin and that on early diabetic rats cochlear histopathology. METHOD: Intraperitoneally inject streptozotocin disposable of dose of 55 mg x kg(-1), so that a model of diabetic rats is created, and treated by, and simultaneously treated by Duxil as matched groups for positive, then observe the blood glucose of each group, the histopathology of cochlear, and any circumstantial change of their microstructures. RESULT: GEPRB can reduce the cumulating thickness of the basilar membrane and that of the vascular pattern, so as to tighten up the sparsity of the spiral ganglion cells. CONCLUSION: GEPRB is rather effective on hypoglycemic for the diabetic rat model, and therapeutic goal can be achieved by improving the pathological changes of the cochlea damaged. The improvement by GEPRB for microangiopathic change of the cochlea capillary is probably the pathological basis of relieving hearing loss.

Antinociceptive and anti-inflammatory activities of iridoid glycosides extract of Lamiophlomis rotata (Benth.) Kudo.

Lamiophlomis rotata (Benth.) Kudo is a perennial herb (Labiatae) used as the Tibetan traditional medicine with the effects of alleviating pain, detumescence, hemostasis, promoting blood circulation to remove blood stasis and reinforcing marrow. In this study, we investigated the antinociceptive and anti-inflammatory activities of iridoid glycosides extract of L. rotata (IGLR) in mice. Our results showed that the iridoid glycosides extract could decrease acetic-acid-induced writhings times and formalin-induced lickings times, inhibit carrageenan-induced hind paw edema and xylene-induced ear swelling, and suppress peritoneal capillary permeability and leukocyte infiltration also induced by acetic acid in mice. All of these results suggested that the iridoid glycosides extract possesses the significant antinociceptive and anti-inflammatory activities.