In vitro Anti-inflammatory Activity of Ligustrum vulgare Extracts and Their Analytical Characterization

Interest in the anti-inflammatory effects of Ligustrum vulgare L., which has been used traditionally in China and Japan prompted us to determine anti-inflammatory effects of the plant's compounds in leukocytes. The leaves of L. vulgare were used to prepare a decoction which was successively extracted with organic solvents (dichloromethane (DCM), n-butanol, ethyl acetate) using liquid-liquid partition. Extracts were tested for inhibition of LTB4, resp. PGE2 biosynthesis. Each extract was evaluated for its in vitro cyclooxygenase-1/2 (COX-1/2) inhibitory activity using assays with purified COX-1 and COX-2 enzymes, as well as for their LTB4 formation inhibitory activity using an assay with activated human neutrophil granulocytes. All extracts reported inhibitory actions against COXs in comparison with the synthetic inhibitors NS-398 (IC50 = 2.6 μM) and indomethacin (IC50 = 0.9 μM). The dichloromethane extract of privet leaves showed a considerable inhibitory effect against COX-1 and COX-2 enzyme activity. The DCM extract revealed 2.7 times higher inhibitory activity against LTB4 formation in comparison with the known specific LT inhibitor zileuton (IC50 = 5.0 μM). Additionally, oleuropein and echinacoside were detected by HPLC-DAD and LC-MS in the Ligustrum vulgare leaves. Both compounds exhibited weak inhibitory activity on cyclooxygenases and leukotriene formation.

Download Full-text

Design, Synthesis and Pharmacological Evaluation of Gastro- Protective Anti-inflammatory Analgesic Agents based on Dual Oxidative Stress / Cyclooxygenase Inhibition

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry ◽

10.2174/1871523018666190325155244 ◽

2020 ◽

Vol 19 (3) ◽

pp. 268-290 ◽

Cited By ~ 1

Author(s):

Monika Gaba ◽

Sarbjot Singh ◽

Chander Mohan ◽

Richa Dhingra ◽

Monika Chauhan ◽

...

Keyword(s):

Antioxidant Activity ◽

Inhibitory Activity ◽

Frap Assay ◽

Anti Oxidant ◽

Cox 2 ◽

Anti Inflammatory ◽

Analgesic Activities ◽

Cox 1

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) derived local generation of reactive oxygen species (ROS) plays a crucial role in the formation of gastric ulceration. Objective: Therefore, anti-inflammatory analgesics with potent antioxidant activity could be a potential therapeutic strategy for the treatment of pain and inflammatory disorders without gastrointestinal (GI) side effects. Methods: In an effort to develop gastroprotective analgesic and anti-inflammatory agents, a series of 2-methylamino-substituted-1H-benzo[d] imidazol-1-yl) (phenyl) methanone derivatives were synthesized and evaluated in vitro for cyclooxygenase (COX) inhibition as well as anti-oxidant potential by the FRAP assay. The compounds with significant in vitro COX-1/COX-2 inhibitory activity and antioxidant activity were further screened in vivo for their anti-inflammatory and analgesic activities. Moreover, the ulcerogenic potential of test compounds was also studied. To gain insight into the plausible mode of interaction of compounds within the active sites of COX-1 and COX-2, molecular docking simulations were performed. Results: Among the various synthesized molecules, most of the compounds showed good cyclooxygenase inhibitory activity and efficient antioxidant activity in FRAP assay. After preliminary and indicative in vitro assays, three compounds exhibited most significant antiinflammatory and analgesic activity with better gastric tolerability during their in vivo evaluation. Ligand interaction studies indicated highest dock score -43.05 of 1,2- disubstituted benzimidazole derivatives in comparison to the reference ligand -30.70. Overall studies provided us (2-((4-methoxyphenylamino) methyl) -1h-benzo [d] imidazol- 1-yl) (phenyl) methanone as a lead with potent gastro-protective anti-inflammatory and analgesic activities that can be used for future research. Conclusion: From the above results, it can be concluded that designing of multifunctional molecules with COX-1/COX-2 inhibitory and anti-oxidant activities could hold a great promise for further development of GI-safer NSAIDs.

Download Full-text

Modulation of Enzyme-Catalyzed Synthesis of Prostaglandins by Components Contained in Kidney Microsomal Preparations

Molecules ◽

10.3390/molecules27010219 ◽

2021 ◽

Vol 27 (1) ◽

pp. 219

Author(s):

Hyoung-Woo Bai ◽

Jina Yu ◽

Yue Wang ◽

Pan Wang ◽

Baoting Zhu

Keyword(s):

Acid Metabolism ◽

Inhibitory Effect ◽

Arachidonic Acid Metabolism ◽

Microsomal Preparation ◽

Pig Kidney ◽

Cyclooxygenase 1 ◽

Kidney Microsomes ◽

Cox 2 ◽

Cox 1

In the kidney, prostaglandins formed by cyclooxygenase 1 and 2 (COX-1 and COX-2) play an important role in regulating renal blood flow. In the present study, we report our observations regarding a unique modulatory effect of renal microsomal preparation on COX-1/2-mediated formation of major prostaglandin (PG) products in vitro. We found that microsomes prepared from pig and rat kidneys had a dual stimulatory–inhibitory effect on the formation of certain PG products catalyzed by COX-1 and COX-2. At lower concentrations, kidney microsomes stimulated the formation of certain PG products, whereas at higher concentrations, their presence inhibited the formation. Presence of kidney microsomes consistently increased the Km values of the COX-1/2-mediated reactions, while the Vmax might be increased or decreased depending on stimulation or inhibition observed. Experimental evidence was presented to show that a protein component present in the pig kidney microsomes was primarily responsible for the activation of the enzyme-catalyzed arachidonic acid metabolism leading to the formation of certain PG products.

Download Full-text

Targeted Lignan Profiling and Anti-Inflammatory Properties of Schisandra rubriflora and Schisandra chinensis Extracts

Molecules ◽

10.3390/molecules23123103 ◽

2018 ◽

Vol 23 (12) ◽

pp. 3103 ◽

Cited By ~ 11

Author(s):

Agnieszka Szopa ◽

Michał Dziurka ◽

Angelika Warzecha ◽

Paweł Kubica ◽

Marta Klimek-Szczykutowicz ◽

...

Keyword(s):

Total Content ◽

Leaf Extracts ◽

Fruit Extracts ◽

Phospholipases A2 ◽

Cyclooxygenase 1 ◽

Gomisin A ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 1

Schisandra rubriflora is a dioecious plant of increasing importance due to its lignan composition, and therefore, possible therapeutic properties. The aim of the work was lignan profiling of fruits, leaves and shoots of female (F) and male (M) plants using UHPLC-MS/MS. Additionally, the anti-inflammatory activity of plant extracts and individual lignans was tested in vitro for the inhibition of 15-lipooxygenase (15-LOX), phospholipases A2 (sPLA2), cyclooxygenase 1 and 2 (COX-1; COX-2) enzyme activities. The extracts of fruits, leaves and shoots of the pharmacopoeial species, S. chinensis, were tested for comparison. Twenty-four lignans were monitored. Lignan contents in S. rubriflora fruit extracts amounted to 1055.65 mg/100 g DW and the dominant compounds included schisanhenol, aneloylgomisin H, schisantherin B, schisandrin A, gomisin O, angeloylgomisin O and gomisin G. The content of lignan in leaf extracts was 853.33 (F) and 1106.80 (M) mg/100 g DW. Shoot extracts were poorer in lignans—559.97 (F) and 384.80 (M) mg/100 g DW. Schisantherin B, schisantherin A, 6-O-benzoylgomisin O and angeloylgomisin H were the dominant compounds in leaf and shoot extracts. The total content of detected lignans in S. chinensis fruit, leaf and shoot extracts was: 1686.95, 433.59 and 313.83 mg/100 g DW, respectively. Gomisin N, schisandrin A, schisandrin, gomisin D, schisantherin B, gomisin A, angeloylgomisin H and gomisin J were the dominant lignans in S. chinensis fruit extracts were. The results of anti-inflammatory assays revealed higher activity of S. rubriflora extracts. Individual lignans showed significant inhibitory activity against 15-LOX, COX-1 and COX-2 enzymes.

Download Full-text

ANTI-INFLAMMATORY ACTIVITY OF BACTERIA ASSOCIATED WITH MARINE SPONGE (HALICLONA AMBOINENSIS) VIA REDUCTING NO PRODUCTION AND INHIBITING CYCLOOXYGENASE-1, CYCLOOXYGENASE-2, AND SECRETORY PHOSPHOLIPASE A2 ACTIVITIES

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i11.20094 ◽

2017 ◽

Vol 10 (11) ◽

pp. 95 ◽

Cited By ~ 1

Author(s):

Yosie Andriani ◽

Leni Marlina ◽

Habsah Mohamad ◽

Hermansyah Amir ◽

Siti Aisha M Radzi ◽

...

Keyword(s):

Methanol Extract ◽

Inflammatory Activity ◽

No Production ◽

Secretory Phospholipase A2 ◽

Phytochemical Screening ◽

Spla2 Activity ◽

Cyclooxygenase 1 ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 1

Objective: This study aimed to investigate the anti-inflammatory activity of methanol extract and fractions of bacteria associated with sponge (Haliclona amboinensis) and to evaluate their effect in reducing NO production and inhibiting cyclooxygenase-1 (COX-1), cyclooxgenase-2 (COX-2) and secretory phospholipase A2 (sPLA2) activity.Methods: All bacterial isolates were cultured and supernatants were collected for the extraction of secondary metabolites using diaion HP-20 to obtain methanol extracts. Evaluation of cytotoxicity property was carried out on macrophage cell lines (RAW264.7) by 3-(4,5-dimethylthiazol- 2-yl) 2,5-diphenyl tetrazoliumbromide assay. Anti-inflammatory screening was done by inducible nitric oxide assay on RAW264.7 cell lines with lipopolysaccharide (LPS) stimulation. Dianion HP-20 was used to remove salt content. A selected methanol extract was subjected to further fractionations by C-18 reverse phase and their anti-inflammatory potential was evaluated by COX-1 and COX-2, and sPLA2 enzymatic assay.Results: Seven methanol extracts showed no cytotoxic property against RAW 264.7 cell line (inhibitory concentration 50% > 30 μg/ml) and selected for anti-inflammatory screening assay. Result showed methanol extract HM 1.2 reduced NO production >80% and it has been selected for phytochemical screening, further fractionations and assay. Phytochemical screening showed alkaloids and terpenoids present in the HM 1.2. The HM 1.2 and its fractions (F1, F2, F1C1, F1C2, F1C3, and F1C4) were proven to inhibit COX-1, COX-2, and sPLA2 activity in the range of 60.516-116.886%, 20.554- 116.457%, and 70.2667-114.8148%, respectively.Conclusions: This study revealed that bacteria associated with H. amboinensis have produced anti-inflammatory activity via reducing NO production and inhibiting COX-1, COX-2, and sPLA2 activity.

Download Full-text

Evaluation of Anti-Inflammatory Components of Guizhi Fuling Capsule, an Ancient Chinese Herbal Formula, in Human Umbilical Vein Endothelial Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/2029134 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Yuzhong Zheng ◽

Guizhong Xin ◽

Guowei Gong ◽

Tina TX Dong ◽

Ping Li ◽

...

Keyword(s):

Endothelial Cells ◽

Umbilical Vein ◽

Active Components ◽

Human Umbilical Vein ◽

Cellular Inflammation ◽

Cyclooxygenase 1 ◽

Cox 2 ◽

Anti Inflammatory ◽

Umbilical Vein Endothelial Cells ◽

Cox 1

Background. Guizhi Fuling capsule (GFC), a well-known formula composed of five medicinal herbs, is commonly prescribed to treat primary dysmenorrhea, as well as to achieve good clinical efficacy in China. However, the active components of GFC have not been identified. Here, the anti-inflammatory functions of GFC, as well as its major ingredients, were evaluated in human umbilical vein endothelial cells (HUVECs). Methods. Lipopolysaccharide (LPS) was used in HUVECs to imitate the cellular inflammation. Then, GFC-triggered mRNA expressions of cyclooxygenase-1 (COX-1) and COX-2 were determined by real-time PCR, while the expression of COX-2 protein was revealed by western blotting. Besides, nine components of GFC were evaluated for their contribution value in the anti-dysmenorrhea effects Results. The application of GFC downregulated the mRNA expressions of COX-1 and COX-2 mRNAs. Nine major components of GFC were tested in the inflammatory system, and three compounds, including paeoniflorin, benzoylpaeoniflorin, and amygdalin, exhibited robust activation in HUVECs. The combination of paeoniflorin, benzoylpaeoniflorin, and amygdalin showed over 80% of the anti-inflammatory activation. Conclusion. Our study supports that GFC plays a promising role in anti-dysmenorrhea function by decreasing COXs’ expression. Besides, paeoniflorin, benzoylpaeoniflorin, and amygdalin could be considered as major regulators for the anti-dysmenorrhea effects of GFC.

Download Full-text

New indomethacin analogs as selective COX‐2 inhibitors: Synthesis, COX‐1/2 inhibitory activity, anti‐inflammatory, ulcerogenicity, histopathological, and docking studies

Archiv der Pharmazie ◽

10.1002/ardp.202000328 ◽

2020 ◽

Author(s):

Khaled R. A. Abdellatif ◽

Eman K. A. Abdelall ◽

Heba A. H. Elshemy ◽

El‐Shaymaa El‐Nahass ◽

Maha M. Abdel‐Fattah ◽

...

Keyword(s):

Inhibitory Activity ◽

Docking Studies ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 2 Inhibitors ◽

Cox 1

Download Full-text

Synthesis of Novel Benzodifuranyl; 1,3,5-Triazines; 1,3,5-Oxadiazepines; and Thiazolopyrimidines Derived from Visnaginone and Khellinone as Anti-Inflammatory and Analgesic Agents

Molecules ◽

10.3390/molecules25010220 ◽

2020 ◽

Vol 25 (1) ◽

pp. 220 ◽

Cited By ~ 6

Author(s):

Ameen Ali Abu-Hashem ◽

Sami A Al-Hussain ◽

Magdi E. A. Zaki

Keyword(s):

Sodium Ethoxide ◽

Standard Drug ◽

Chemical Structures ◽

Cyclooxygenase 1 ◽

Analgesic Agents ◽

Cox 2 ◽

Anti Inflammatory ◽

New Compounds ◽

Cox 2 Inhibitors ◽

Cox 1

Novel (4-methoxy or 4,8-dimethoxy)-3-methyl-N-(6-oxo-2-thioxo-1,2,3, 6-tetrahydro- pyrimidin-4-yl) benzo [1,2-b: 5, 4-b’] difuran-2-carboxamide (5a–b) has been synthesized by the reaction of visnagenone–ethylacetate (2a) or khellinone–ethylacetate (2b) with 6-aminothiouracil in dimethylformamide or refluxing of benzofuran-oxy-N-(2-thioxopyrimidine) acetamide (4a–b) in sodium ethoxide to give the same products (5a,b) in good yields. Thus, compounds 5a–b are used as an initiative to prepare many new heterocyclic compounds such as 2-(4-(3-methylbenzodifuran- 2-carbox-amido) pyrimidine) acetic acid (6a–b), N-(thiazolo[3, 2-a]pyrimidine)-3-methylbenzo- difuran-2-carboxamide (7a–b), N-(2-thioxopyrimidine)-methylbenzodifuran-2-carbimidoylchloride (8a–b), N-(2-(methyl-thio) pyrimidine)-3-methylbenzodifuran-2-carbimidoylchloride (9a–b), N-(2, 6 -di(piperazine or morpholine)pyrimidine)-1-(3-methylbenzodifuran)-1-(piperazine or morpholine) methanimine(10a–d), 8-(methylbenzodifuran)-thiazolopyrimido[1,6-a][1,3,5]triazine-3,5-dione (11a –b), 8-(3-methyl benzodifuran)-thiazolopyrimido[6,1-d][1,3,5]oxadiazepine-trione (12a–b), and 2,10 -di(sub-benzylidene)-8-(3-methylbenzodifuran)-thiazolopyrimido[6,1-d][1,3,5]oxadiazepine-3,5,11- trione (13a–f). All new chemical structures were illustrated on the basis of elemental and spectral analysis (IR, NMR, and MS). The new compounds were screened as cyclooxygenase-1/ cyclooxygenase-2 (COX-1/COX-2) inhibitors and had analgesic and anti-inflammatory activities. The compounds 10a–d and 13a–f had the highest inhibitory activity on COX-2 selectivity, with indices of 99–90, analgesic activity of 51–42% protection, and anti-inflammatory activity of 68%–59%. The inhibition of edema for the same compounds, 10a–d and 13a–f, was compared with sodium diclofenac as a standard drug.

Download Full-text