Antioxidant and anti-inflammatory effects in lipopolysaccharide-induced THP-1 cells of coumarins from the bark of Hesperethusa crenulata R.

All parts of Thanakha (Hesperethusa crenulata R.) have been used as traditional skin care herbal material in Myanmar. In this study, coumarins from H. crenulata R. bark were isolated through solvent extraction, systematic solvent fractionation, and repeated column chromatography. Spectroscopic analyses using ESI–MS, 1D NMR (1H and 13C), 2D NMR (gHSQC and gHMBC), specific rotation, circular dichroism, and IR spectrometry revealed three coumarins 2R-7-hydroxy-8-(2,3-dihydroxy-3-methylbutyl)-coumarin (compound 1), peucedanol (compound 2), and methylpeucedanol (compound 3), which were first isolated from Thanakha tree. Antioxidant capacities of three coumarins decreased as follows: compound 2 > compound 3 > compound 1. Treatments of lipopolysaccharide-induced THP-1 human monocytic cells with compounds 2 and 3 at 378.8 μM and 359.7 μM inhibited tumor necrosis factor-α production by approximately 32.7% and 13.3%, respectively, compared with the negative control. In summary, these results suggest that Thanakha bark extracts can be used as a potent antioxidant and anti-inflammatory source for cosmetic ingredients.

Osthole Attenuates Macrophage Activation in Experimental Asthma by Inhibitingthe NF-ĸB/MIF Signaling Pathway

Inhibition of activated macrophages is an alternative therapeutic strategy for asthma. We investigated whether a coumarin compound, osthole, isolated from Cnidiummonnieri (L.) Cuss, alleviated macrophage activation in vivo and in vitro. Osthole could reduce expression of a marker of activated macrophages, cluster of differentiation (CD)206, in an ovalbumin-challenge model of asthma in mice. Osthole could also inhibit infiltration of inflammatory cells, collagen deposition and production of proinflammatory cytokines [interleukin (IL)-1β, tumor necrosis factor-ɑ, macrophage migration inhibitory factor (MIF)] in asthmatic mice. In vitro, expression of phosphorylated-IĸBɑ, MIF and M2 cytokines (Ym-1, Fizz-1, arginase-1) in IL-4-induced macrophages decreased upon exposure to the NF-ĸB inhibitor MG-132. In our short hairpin (sh)RNA-MIF-knockdown model, reduced expression of M2 cytokines was detected in the IL-4 + shRNA-MIF group. Osthole could attenuate the proliferation and migration of an IL-4-induced rat alveolar macrophages line (NR8383). Osthole could reduce IL-4-induced translocation of nuclear factor-kappa B (NF-ĸB) in NR8383 cells. Collectively, our results suggest that osthole ameliorates macrophage activation in asthma by suppressing the NF-ĸB/MIF signaling pathway, and might be a potential agent for treating asthma.

A new coumarin compound DCH combats methicillin-resistant Staphylococcus aureus biofilm by targeting arginine repressor

Staphylococcus aureus infection is difficult to eradicate because of biofilm formation and antibiotic resistance. The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection necessitates the development of a new agent against bacterial biofilms. We report a new coumarin compound, termed DCH, that effectively combats MRSA in vitro and in vivo and exhibits potent antibiofilm activity without detectable resistance. Cellular proteome analysis suggests that the molecular mechanism of action of DCH involves the arginine catabolic pathway. Using molecular docking and binding affinity assays of DCH, and comparison of the properties of wild-type and ArgR-deficient MRSA strains, we demonstrate that the arginine repressor ArgR, an essential regulator of the arginine catabolic pathway, is the target of DCH. These findings indicate that DCH is a promising lead compound and validate bacterial ArgR as a potential target in the development of new drugs against MRSA biofilms.

Preparation and Analysis of Coumarin Compound for New Application

Numerous normally occurring substances usually applied in famous drugs the world over, incorporate the coumarin moiety. Coumarin speaks to a unique platform for restorative scientists, in light of its unconventional physicochemical highlights, and the adaptable and easy engineered change right into a huge assortment of functionalized coumarone. As an outcome, countless coumarin subordinates were dependent, incorporated, and tried to cope with numerous pharmacological focuses in a particular way, e.G., specific chemical inhibitors, and all of the extra as of past due, numerous chose targets (multitarget ligands) associated with multifactorial illnesses, as an instance, Parkinson's and Alzheimer's infections. In this survey, a definition of today's manufactured paths prompting mono-and polyfunctionalized coumarins might be introduced, alongside the precept natural pathways in their biosynthesis and metabolic adjustments. The numerous current and overdue audits in the discipline provoked us to type-specific terrific alternatives. Subsequently, the survey is targeted around following up on chosen focuses on neurodegenerative illnesses.

Theoretical Prediction of Possible Drug Treatment of COVID-19 using Coumarins Containing Chloroquine Moeity

Chloroquine was theoretically reacted with the coumarin compound. Two compounds viz. [N-(7-chloroquinolin-4-yl)-N-(5-(diethylamino)-pentan-2-yl)-4-methyl-2-oxo-2H-chromene-7- sulfonamide] (3) and [N-(7-chloroquinolin-4-yl)-N-(5-(diethylamino)pentan-2-yl)-4-methyl-2-oxo- 2H-chromene-6-sulfonamide] (4) were suggested. The results showed that compound 4 may influence the COVID-19 treatment. The physico-chemical parameters were determined through theoretical calculations by using Hartree-Fock at different basis sets (6-31G), (STO/3G) and the semi-empirical (AM1) method. The calculations demonstrated the scheme of reaction between coumarin and the chloroquine structure by using the predicted mechanisms. The physical and chemical properties of the predicted compounds were determined to select the optimal form as the candidate for COVID-19 treatment. Compound 4 was more stable than compound 3, with different proteins viz. 6YHU, 6YI3 and 6LU7. Three types of software, including Gaussian 03, Chem-Bio office and molecular operating environment (MOE) were employed.

Inhibitory Effect of Osthole from Cnidium monnieri on Tobacco Mosaic Virus (TMV) Infection in Nicotiana glutinosa

The coumarin compound of osthole was extracted from Cnidium monnieri and identified by LC-MS and 1H- and 13C-NMR. Osthole was tested for anti-virus activity against tobacco mosaic virus (TMV) using the half-leaf method. The results showed that stronger antiviral activity on TMV infection appeared in Nicotiana glutinosa than that of eugenol and ningnanmycin, with inhibitory, protective, and curative effects of 72.57%, 70.26%, and 61.97%, respectively. Through observation of the TMV particles, we found that osthole could directly affect the viral particles. Correspondingly, the level of coat protein detected by Western blot was significantly reduced when the concentrations of osthole increased in tested plants compared to that of the control. These results suggest that osthole has anti-TMV activity and may be used as a biological reagent to control the plant virus in the half-leaf method.

Resveratrol inhibit interleukin-1β induced inflammatory response in human osteoarthritis chondrocytes through NF-κB signaling pathway

Osteoarthritis (OA) is a common degenerative disease and affect millions of people. Resveratrol is a coumarin compound refined from traditional Chinese medicines with potential anti-inflammatory ability. This study aimed to evaluate protective anti-inflammatory effects of resveratrol in human OA chondrocytes. The chondrocytes were isolated from OA patients. CCK-8 method was used to explore the optimal dose of resveratrol for chondrocyte. Next, we used PCR and Western-blot method to assess the relative mRNA and protein expression in IL-1β group. We further explored relevant mechanism of resveratrol for anti-inflammatory in human OA chondrocytes by immunofluorescence and Western-blot. The results showed that resveratrol blocked IL-1β-stimulated production of NO and PGE2. In addition, resveratrol inhibited the expression of COX-2, iNOs, MMP-1, MMP-3, MMP-13, and increased the levels of aggrecan and collagen-II. Mechanistically, resveratrol suppressed IL-1β-induced IκB-α degradation and NF-κB activation. In conclusion, our results demonstrate that resveratrol inhibits inflammation in OA via the regulation of NF-κB signaling pathway, and suggested that resveratrol may be a potential therapeutic agent for OA.