Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) - Volume 18, Issue 1, 2019

Background: A novel series of 2-(Morpholin-4-yl)-N-phenylquinazolin-4- amine derivatives were synthesized and confirmed with spectral and elemental techniques. Methods: The compounds were tested for analgesic and anti-inflammatory activity by various pain models in rodents whereas the selectivity towards COX-2 receptor is determined by in vitro assay. Results: Screening results of compounds exhibited comparable biological activity with that of standard compound Indomethacin used for study. Compound 5d was found to be significantly potent with respect to its anti-inflammatory and analgesic activity with substantial COX-II selectivity. Conclusion: In silico analysis by molecular docking and 3D-QSAR studies justifies activity profile of compound 5d, suggesting that it may have potential for further evaluation and development as lead molecule for therapy in pain management.

Introduction: Betamethasone dipropionate is a highly effective corticosteroid anti-inflammatory. However, the main drawback of its topical use is the limited skin penetration into deeper skin layers. Also, its systemic use has shown many side effects. Objective: The goal of this research was to formulate betamethasone dipropionate in nanostructured lipid carriers (NLC) formulae that contain oleic acid to aid its penetration to deeper skin layers and to aid absorption to local regions upon topical application. Methods: NLC formulae were prepared by high shear homogenization then sonication. Formulae were characterized for their particle size, size distribution, electric potential, occlusion factor, entrapment efficiency, drug loading, transmission electron microscopy, in vitro drug release, and ex vivo skin penetration. Compatibility of ingredients with drug was tested using differential scanning calorimetry. Formulae were shown to have appropriate characteristics. NLC formulae were superior to traditional topical formulation in drug release. Results: Upon testing ex vivo skin penetration, betamethasone dipropionate prepared in NLC formulae was shown to penetrate more efficiently into skin layers than when formulated as a traditional cream. NLC formulation that contained higher percentage of oleic acid showed higher penetration and higher amount of drug to pass through skin. Conclusion: In general, NLC with lower oleic acid percentage was shown to deliver betamethasone dipropionate more efficiently into deeper skin layers while that of a higher oleic acid percentage was shown to deliver the drug more efficiently into deeper skin layers and through the skin, transdermally.

Background: Polygonum odoratum is an indigenous vegetable that has been used as a favoring agent and also used as a Thai traditional medicine to treat flatulence. Objective: To analyze active ingredients, total phenolic and total flavonoid contents, antiinflammatory and antioxidant activities from leaf and stem extracts of P. odoratum. Methods: Leaves and stems were dried and extracted by using methanol, dichloromethane and water for obtaining Methanolic Leaf Extract (MLE), Methanolic Stem Extract (MTE), Dichloromethane Leaf Extract (DLE), Dichloromethane Stem Extract (DTE), Water Leaf Extract (WLE) and Water Stem Extract (WTE). The extracts were quantified for total phenolic and total flavonoid contents by spectrophotometry and active compounds were analyzed by using GC-MS. Antioxidant activity was determined by ABTS and DPPH radicals scavenging assays. Anti-inflammatory activity was tested by the inhibition of nitric oxide production in RAW 264.7 macrophage cells induced by lipopolysaccharide. Results: The DLE exhibited the most potent anti-inflammatory effect by inhibiting nitric oxide production in a concentration-dependent manner (IC50 = 53.75±0.72 μg/mL). MLE exhibited strong antioxidant activity and contained the highest concentration of phenolic compounds (52.59±0.58 mg gallic acid equivalent/g extract) and flavonoid (19.97+0.11 mg quercetin equivalent/g extract). E-15-Heptadecenal and 3, 7, 11, 15-tetramethyl-2- hexadecen-1-ol were found predominantly in the methanol extracts. Conclusion: The leaf extract of P. odoratum showed potent anti-inflammatory and antioxidant activities, mediated by DLE and MLE, respectively.

Background: Rheumatoid Arthritis (RA) is a devastating disease characterized by continual addition of leukocytes and T cells within the articular cavity causing inflammation and cartilage destruction. Withania somnifera is one of the most precious medicinal herbs, reported to have antioxidant, anti128;inflammatory, and immunomodulatory properties. Objective: The purpose of this study was to evaluate anti-inflammatory activity of aqueous extract of Withania somnifera roots (WSAq) in Collagen Induced Arthritic (CIA) rats. Methods: To achieve this, we assessed the level of inflammatory cytokines such as Tumor Necrosis Factor (TNF)-α, IL-1β, IL-6 and IL-10 in CIA rats. Further, transcription factor, oxidative stress parameters and CD+8 expressions were also analyzed in CIA rats. Results: Arthritic rats showed a greater increase in the levels of pro inflammatory cytokines such as TNF-α, IL-1β, IL-6, transcription factor NF-ΚB and a decrease in IL-10 concentration than controls rats. Oral administration of WSAq at a dose of 300mg/kg.wt. (WSAq300) appreciably attenuated the production of these pro inflammatory cytokines. This anti-inflammatory activity of WSAq300 might be partly mediated through an increase in the secretion of IL-10 and inhibition of NF-ΚB activity. Further, arthritic rats also show increased oxidative stress as compared to control rats. This increased oxidative stress in the arthritic rats appears to be the outcome of both an activated pro-oxidant and a poor antioxidant defense system. Treatment with WSAq300 strongly ameliorates all these ROS parameters significantly to near normal. Additional, metalloproteinase MMP-8 levels were also measured and found to be increased in CIA rats, which after treatment with WSAq300 came down to near normal. Conclusion: From the above results, it can be concluded that the use of WSAq300 may be a valuable supplement which can improve human arthritis.

Background: Chronic inflammation is a critical health issue and implicated in several chronic health problems such as tumors, auto-immune disorder, hypertension or diabetes. However, Juniperus procera is one of the famous ancient plants that has been traditionally used to treat several diseases such as hyperglycemia, hepatitis, jaundice, bronchitis, and pneumonia. Objective: Current study is an attempt to investigate the anti-inflammatory effect of Juniperus procera extract on rats exposed to cytotoxicity caused experimentally by streptozotocin injections. Methods: Five groups of adult Wistar rats (10 rats each) were examined as (Normal control, Normal rats treated with Juniperus procera extract, rats administrated with streptozotocin, rats administrated with streptozotocin and treated with insulin and, rats administrated with streptozotocin and Juniperus procera extract). At the end of the experiment, blood was collected from experimented rats. Animals then were killed and small parts of both pancreas and liver were collected for gene expression and histopathological examination. Results: Serum analysis showed a significant increase in glucose, IL-6, IL-2 and TNF-α levels in rats exposed to streptozotocin. That change was reduced in rats cotreated with insulin or Juniperus procera extract. Moreover, streptozotocin showed a significant upregulation of IL-6, TNF-α and A2M genes, while, either insulin or Juniperus procera treatment was restored to normal status. Streptozotocin induced inflammation within hepatic tissues which clearly reduced in hepatic tissues of both insulin and junipers cotreated groups. Conclusion: Streptozotocin toxicity induces acute inflammation and increases serum glucose, IL-6, IL-2 and TNF-α levels. However, Juniperus procera extract was found to significantly prevent that reaction within four weeks experimented frame time.