Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) - Volume 16, Issue 2, 2017

Background: Salvia species are known for their biological properties in many countries and might potentially provide novel therapeutic agents. This review provides an overview of the available literature on the anti-inflammatory and antioxidant effects of Salvia species. Methods: Using bibliographic databases, particularly PubMed, this review aims to add new information to the list of Salvia species, including S. ceratophylla, S. chloroleuca, S. fruticosa, S. lachostachys, S. lavandulifolia, S. miltiorrhiza, S. mirzayanii, S. officinalis, S. plebeia, S. verbenaca, and S. virgata, and their main constituents as promising antiinflammatory and antioxidant agents, highlighting their mode of action. Results: Salvia species are sources of health-promoting phytochemicals that comprise polyphenols, flavonoids, terpenes and several other constituents. Many studies have indicated that plants from the Salvia genus reduce the oxidative stress and may be able to prevent and/or to treat inflammatory diseases. These potential beneficial effects have been attributed to the presence of compounds that show antioxidant properties and that demonstrated to inhibit the molecular targets of pro-inflammatory mediators in inflammatory responses. Conclusion: Salvia species and their secondary metabolites may be potential agents to improve the quality of life in patients with inflammatory diseases.

Objective: The oxidative process in atherogenesis generated by proinflammatory induction and response to antioxidants vitamins in an experimental model were analyzed. Methods: Male rats were used: (A)Control, (B)Control+vitamin E plus C, (C)Hyperfibrinogenemia and (D)Hyperfibrinogenemia+vitamins E plus C. Hyperfibrinogenemia induced by daily injection of adrenaline (0.1mg/day/rat) for 120 days. Treatment: 3.42 mg/kg of vitamin E plus 2.14 mg/kg of vitamin C, fifteen days after induction. Vascular histology analyzed by optical microscopy. Fibrinogen, nitrites and superoxide dismutase analyzed by spectrophotometry. Statistics: MANOVA, Hotelling test for post testing, significance level p<0.05. Results: (C) group showed higher fibrinogen than (A) and (B)(p<0.001). Compared to (C) group, (D) showed a decrease of fibrinogen (p<0.001). A marked increase in nitrites was found in (C) versus (A), (B) and (D) groups (p<0.001). Superoxide dismutase activity increased in (C) group compared to groups (A) and (B) (p<0.001). In the group (D) an increase of the activity of this enzyme was observed in comparison to groups (C)(p<0.001), (A) and (B) (p<0.0001 in both). The (C) group shown endothelial denudation, thickening of the vascular intima and extracellular matrix enlargement with foam cells(p<0.001). Conclusion: These results strongly suggest that vitamins E plus C produce regression of inflammatory and oxidative stress processes in this experimental model.

Background: We have developed a novel aqueous polyherbal formulation (SIRB-001) consisting of 3 herbs; Rheum palmatum L., Lonicera Japonica and Rehmannia glutinosa Libosch in the ratio 1:1:3. SIRB-001 has demonstrated efficacious effects in psoriasis patients. Objective: This study was aimed at scientifically evaluating the in vitro antipsoriatic activity of SIRB-001. Method: The in vitro anti-psoriatic properties of SIRB-001 were assessed in human keratinocyte cell line; HaCaT. Anti-proliferative effect was studied using MTT assay. Apoptosis was examined by flow cytometry and colorimetric methods. Inflammatory markers and VEGF were determined by ELISA. IL-17/IL-23 secretion was assessed in immune cells. Signaling markers (kinases) by enzymatic assay and Topoisomerase-II activity by Kinetoplast DNA Cleavage assay was tested. Results: SIRB-001 significantly inhibited (p<0.01) proliferation of HaCaT cells and induced apoptosis. Significant (p<0.01) downregulation of pro-inflammatory markers (TNF- α, IFN-γ, IL-6, NO, sPLA2) and VEGF was observed. IL-17/IL-23 secretion was significantly (p<0.01) alleviated in immune cells (RAW264.7 and THP-1). Inhibition of signaling markers (AKT1, FLT3, MAPK1, PRKCA, MAP2K) was observed. SIRB-001 demonstrated inhibition of Topoisomerase-II activity. High Performance Liquid Chromatography (HPLC) analysis of SIRB-001 was carried out using standard marker compounds chlorogenic acid (tR=13.98min), Acteoside (tR=24.22 min) and Rhein (tR=53.76 min). Conclusion: The in vitro results substantiate the anti-psoriatic effect of SIRB-001 in patients. SIRB-001 exerted anti-psoriatic effects at cellular level via multiple arms (antiproliferative, pro-apoptotic, anti-inflammatory, anti-angiogenic). This study provides insight into mechanism of action of SIRB-001 and highlights its promising potential for development as a herbal therapeutic agent for psoriasis, emphasizing the need of further pharmacological evaluation and toxicological studies.

Background and Objectives: Neurodegenerative diseases and inflammation are always linked to each other; therefore the elaboration of new chemical compounds, which interact with pharmacological targets involved into these two processes, can become one of ways of correction of these types of human CNS pathology. In the field of this problem the anti-inflammatory activity of ten 3-amino derivatives of quinolizidine alkaloid (-)-cytisine (the data about nootropic activity of these compounds are outlined by us previously) was studied by using in vivo, in vitro and in silico approaches. Methods: The anti-inflammatory activity of novel compounds was investigated on carrageenan- induced model of inflammation in Rat paw following an established protocol. COX-1 (ovin) and COX-2 (human recombinant) inhibition activities of tested compounds assessed using a COX Fluorescent Inhibitor Screening Assay Kit. And as part of an in silico screening the leading compounds were docked into the tyrosine sites of COX-1/COX-2 enzymes (PDB code: 1DIY and 1CVU). Results: It was established that ability of 3-(2-hydroxyphenyl)amino, 3-(4-hydroxyphenyl) amino and 3-(3-phenylprop-2-en-1-yl)amino derivatives of 12-N-metylcytisine to inhibit the carrageenan-induced paw oedema in rats is comparable with reference drug diclofenac. The results of in vitro COX-1/COX-2 inhibition assay showed no significant activity of tested compounds, except compounds with 2-hydroxyphenyl, 3-phenylprop-2-en-1-yl, furyl and thiophenyl fragments which slightly reduce the activity of COX-2. Conclusion: The tendency to occurrence of anti-inflammatory properties of synthesized derivatives of quinolizidine alkaloid (-)-cytisine can be explained on the basis of molecular docking results, which assume the possibility of interaction of more potent compounds with key amino acids of COX-1/COX-2 active sites.

Background: Studies on anti-inflammatory and antimicrobial agents remains a challenging and important area in medicinal chemistry research due to more toxic and rapid development of resistance against first effective drugs. In search of novel anti-inflammatory and antimicrobials agents, bisthiourea derivatives of dipeptide conjugated to 6-fluoro-3- (piperidin-4-yl)benzo[d]isoxazole were synthesized. Methods: The peptides were synthesized by solution phase method and conjugated to 6- fluoro-3-(piperidin-4-yl)benzo[d]isoxazole using 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide (EDCI)/hydroxybenzotriazole (HOBt) as a coupling agent and N-methylmorpholine (NMM) as a base. The protecting group, 2-chlorobenzyloxycarbonyl (2-ClZ) and tertbutyloxycarbonyl (Boc) were deblocked and further reacted with substituted phenyl isothiocyanates to obtain bisthiourea derivatives. Results: The molecules 1-24 were examined for their in vitro anti-inflammatory activity by employing human erythrocyte suspension test and it was found that the IC50 values of 9, 12, 21 and 24 were lower than the IC50 of standard references indomethacin and ibuprofen. Further, all the molecules were also evaluated for their in vitro antibacterial and antifungal activities against various pathogens of human origin by agar well diffusion method. In addition, binding interaction of active molecules (7-12 and 19-24) was performed on active site of cyclooxygenase-2 (COX-2) and Staphylococcus aureus (SA) TyrRS showing good binding profile. Conclusion: Molecular docking result, along with the biological assay data, revealed that the compounds containing electron withdrawing group (F) on phenyl ring of thiourea moiety were potential anti-inflammatory and antimicrobial agents.