The Potential of Vouacapanes from Pterodon Emarginatus Vogel against COVID-19 Cytokine Storm

Purpose: The emergence of the COVID-19 pandemic has led to the search for potential therapeutic responses for various aspects of this disease. Fruits of Pterodon emarginatus Vogel (Fabaceae), sucupira, have been used in Brazilian traditional medicine because of their anti-inflammatory properties, which have been proven in vivo, in vitro, and in silico. Therefore, the aim of this work is to evaluate P. emarginatus oleoresin and isolated diterpenes by in vitro anti-inflammatory models. Methods: In this study, the mechanisms underlying the anti-inflammatory activity of Pterodon emarginatus oleoresin and vouacapanes 6α,19β-diacetoxy-7β,14β-dihydroxyvouacapan (V1), 6α-acetoxy-7β,14β-dihydroxyvouacapan (V2), and methyl 6α-acetoxy-7β-hydroxyvouacapan-17β-oate (V3) were investigated in HaCaT cells. Results: Oleoresin, V2, and V3 inhibited phospholipase A2 (30.78%, 24.96%, and 77.64%, respectively). Both vouacapanes also inhibited the expression of COX-2 (28.3% and 33.17%, respectively). The production of interleukin IL-6 was inhibited by oleoresin by 35.47%. However, oleoresin did not interfere with Nrf-2 expression or IL-8 production. Conclusion: The results support the ethnomedicinal use of P. emarginatus oleoresin as an anti-inflammatory herbal medicine, and also highlight Pterodon emarginatus oleoresin and isolated vouacapanes as an attractive therapeutic approach for COVID-19 through the reduction or chronological control of the inflammatory mediators IL-6, COX-2, phospholipase A2, and INF-y (indirectly) during the SARS-CoV-2 infection process.

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2,5-disubstituted-4-thiazolidinones: Synthesis, anti-inflammatory, free radical scavenging potentials and structural insights through molecular docking

Letters in Organic Chemistry ◽

10.2174/1570178618666210706111055 ◽

2021 ◽

Vol 18 ◽

Author(s):

Jagseer Singh ◽

Pooja A Chawla ◽

Rohit Bhatia ◽

Shamsher Singh

Keyword(s):

Free Radicals ◽

Antioxidant Activities ◽

Radical Scavenging ◽

Assay Method ◽

Acidic Group ◽

Active Compounds ◽

Cox 2 ◽

Anti Inflammatory

: The present work reports synthesis and screening of fifteen 2,5-disubstituted-4-thiazolidinones with different substitutions of varied arylidene groups at imino. The structures of the compounds were confirmed by spectral characterization. The compounds were subjected to in vivo anti-inflammatory and in vitro antioxidant activities. The derivatives possessed remarkable activities quite close to standard drugs used. Unlike conventional non-selective NSAIDs, the synthesized compounds did not contain any acidic group, thereby ensuring a complete cure from ulcers. To further substantiate the claim for safer derivatives, the active compounds were docked against the cyclooxygenase (COX)-2 enzyme. It was found that 4-fluorophenylimino substituent at 2- position and 3-nitro moiety on a 5-benzylidene nucleus of the 4-thiazolidinone derivative fitted in the COX-2 binding pocket. The compounds exhibited remarkable activity in scavenging free radicals, as depicted by the DPPH assay method. The structure-activity relationship was also established in the present work with respect to the nature and position of the substituents. The active compounds were evaluated for drug-like nature under Lipinski’s rule of five, and the toxicity behaviour of active compounds was predicted using ADMETlab software. The compounds have the potential to target degenerative disorders associated with inflammation and the generation of free radicals.

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Rationally synthesized coumarin based pyrazolines ameliorate carrageenan induced inflammation through COX-2/pro-inflammatory cytokine inhibition

MedChemComm ◽

10.1039/c8md00457a ◽

2019 ◽

Vol 10 (3) ◽

pp. 421-430 ◽

Cited By ~ 8

Author(s):

Priyanka Chandel ◽

Anoop Kumar ◽

Nishu Singla ◽

Anshul Kumar ◽

Gagandeep Singh ◽

...

Keyword(s):

Inflammatory Cytokine ◽

Cytokine Inhibition ◽

Cox 2 ◽

Anti Inflammatory

In the present work, coumarin based pyrazolines (7a–g) have been synthesized and investigated for their in vitro and in vivo anti-inflammatory potential.

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Inhibitory Effects of a Sargassum miyabei Yendo on Cutibacterium acnes-Induced Skin Inflammation

Nutrients ◽

10.3390/nu12092620 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2620

Author(s):

Mi-Jin Yim ◽

Jeong Min Lee ◽

Hyun-Soo Kim ◽

Grace Choi ◽

Young-Mog Kim ◽

...

Keyword(s):

Acne Vulgaris ◽

Skin Lesions ◽

Enzyme Linked Immunosorbent Assay ◽

Hacat Cells ◽

Chronic Inflammatory Condition ◽

Cutibacterium Acnes ◽

Anti Inflammatory ◽

Sargassum Miyabei

Acne vulgaris is a chronic inflammatory condition of skin sebaceous follicles. To explore its effects on acne vulgaris, we investigated the antibacterial and anti-inflammatory activities of Sargassum miyabei Yendo (a brown alga) ethanolic extract (SMYEE) on Cutibacterium acnes (C. acnes)-stimulated inflammatory responses, both in vivo and in vitro. To induce inflammation in vivo, C. acnes was intradermally injected into the dorsal skin of mice, to which SMYEE was applied. The antimicrobial activity of SMYEE was evaluated by the determination of minimum inhibitory concentrations (MICs). To explore in vitro anti-inflammatory effects, HaCaT cells were stimulated with C. acnes after treatment with SMYEE. The levels of IL-8 and the underlying molecular effects in C. acnes-stimulated HaCaT cells were assessed by enzyme-linked immunosorbent assay, Western blotting, and an electrophoretic mobility shift assay. Mouse skin lesions improved after treatment with SMYEE (50 μg/mouse). Neutrophil infiltration was significantly reduced in SMYEE-treated compared to SMYEE-untreated skin lesions. SMYEE reversed the C. acnes-induced increase in IL-8 levels in HaCaT cells and suppressed dHL-60 cell migration. SMYEE also inhibited C. acnes-induced phosphorylation of the extracellular signal-regulated kinase and inhibited activator protein-1 signaling. SMYEE may be a useful treatment for C. acnes-induced acne vulgaris.

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Nerolidol Mitigates Colonic Inflammation: An Experimental Study Using both In Vivo and In Vitro Models

Nutrients ◽

10.3390/nu12072032 ◽

2020 ◽

Vol 12 (7) ◽

pp. 2032

Author(s):

Vishnu Raj ◽

Balaji Venkataraman ◽

Saeeda Almarzooqi ◽

Sanjana Chandran ◽

Shreesh K. Ojha ◽

...

Keyword(s):

Nuclear Translocation ◽

In Vitro Models ◽

Mrna Levels ◽

Colonic Inflammation ◽

Tnf Α ◽

Cox 2 ◽

Anti Inflammatory ◽

Ht 29

Nerolidol (NED) is a naturally occurring sesquiterpene alcohol present in various plants with potent anti-inflammatory effects. In the current study, we investigated NED as a putative anti-inflammatory compound in an experimental model of colonic inflammation. C57BL/6J male black mice (C57BL/6J) were administered 3% dextran sodium sulfate (DSS) in drinking water for 7 days to induce colitis. Six groups received either vehicle alone or DSS alone or DSS with oral NED (50, 100, and 150 mg/kg body weight/day by oral gavage) or DSS with sulfasalazine. Disease activity index (DAI), colonic histology, and biochemical parameters were measured. TNF-α-treated HT-29 cells were used as in vitro model of colonic inflammation to study NED (25 µM and 50 µM). NED significantly decreased the DAI and reduced the inflammation-associated changes in colon length as well as macroscopic and microscopic architecture of the colon. Changes in tissue Myeloperoxidase (MPO) concentrations, neutrophil and macrophage mRNA expression (CXCL2 and CCL2), and proinflammatory cytokine content (IL-1β, IL-6, and TNF-α) both at the protein and mRNA level were significantly reduced by NED. The increase in content of the proinflammatory enzymes, COX-2 and iNOS induced by DSS were also significantly inhibited by NED along with tissue nitrate levels. NED promoted Nrf2 nuclear translocation dose dependently. NED significantly increased antioxidant enzymes activity (Superoxide dismutase (SOD) and Catalase (CAT)), Hemeoxygenase-1 (HO-1), and SOD3 mRNA levels. NED treatment in TNF-α-challenged HT-29 cells significantly decreased proinflammatory chemokines (CXCL1, IL-8, CCL2) and COX-2 mRNA levels. NED supplementation attenuates colon inflammation through its potent antioxidant and anti-inflammatory activity both in in vivo and in vitro models of colonic inflammation.

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Synthesis of new ibuprofen hybrid conjugates as potential anti-inflammatory and analgesic agents

Future Medicinal Chemistry ◽

10.4155/fmc-2020-0109 ◽

2020 ◽

Vol 12 (15) ◽

pp. 1369-1386

Author(s):

Siva S Panda ◽

Adel S Girgis ◽

Hitesh H Honkanadavar ◽

Riham F George ◽

Aladdin M Srour

Keyword(s):

Writhing Test ◽

Rat Paw Edema ◽

Analgesic Agents ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Rat Paw ◽

Inhibition Studies

Background: A new set of hybrid conjugates derived from 2-(4-isobutylphenyl)propanoic acid (ibuprofen) is synthesized to overcome the drawbacks of the current non-steroidal anti-inflammatory drugs. Results & methodology: Synthesized conjugates were screened for their anti-inflammatory, analgesic and ulcerogenic properties. Few conjugates were found to have significant anti-inflammatory properties in the carrageenan-induced rat paw edema test, while a fair number of conjugates showed promising peripheral analgesic activity in the acetic acid-induced writhing test as well as central analgesic properties in the in vivo hot plate technique. The newly synthesized conjugates did not display any ulcerogenic liability. Conclusion: In vitro, COX-1 and COX-2 enzyme inhibition studies raveled compound 7e is more selective toward COX-2 compared with ibuprofen.

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Anti-inflammatory Effects of Cavidine In Vitro and In Vivo, a Selective COX-2 Inhibitor in LPS-Induced Peritoneal Macrophages of Mouse

Inflammation ◽

10.1007/s10753-014-0054-4 ◽

2014 ◽

Vol 38 (2) ◽

pp. 923-933 ◽

Cited By ~ 12

Author(s):

Xiaofeng Niu ◽

Hailin Zhang ◽

Weifeng Li ◽

Qingli Mu ◽

Huan Yao ◽

...

Keyword(s):

Peritoneal Macrophages ◽

Cox 2 ◽

Anti Inflammatory

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Inhibitory Effects of Traditional Herbal Formula Pyungwi-San on Inflammatory ResponseIn VitroandIn Vivo

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/630198 ◽

2013 ◽

Vol 2013 ◽

pp. 1-19 ◽

Cited By ~ 12

Author(s):

Ji Young Cha ◽

Ji Yun Jung ◽

Jae Yup Jung ◽

Jong Rok Lee ◽

Il Je Cho ◽

...

Keyword(s):

Nitric Oxide ◽

Inflammatory Mediators ◽

Raw 264.7 Cells ◽

Prostaglandin E ◽

Herbal Formula ◽

Paw Edema ◽

Cox 2 ◽

Anti Inflammatory

Pyungwi-san (PWS) is a traditional basic herbal formula. We investigated the effects of PWS on induction of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), pro-inflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α)) and nuclear factor-kappa B (NF-κB) as well as mitogen-activated protein kinases (MAPKs) in lipopolysaccharide-(LPS-) induced Raw 264.7 cells and on paw edema in rats. Treatment with PWS (0.5, 0.75, and 1 mg/mL) resulted in inhibited levels of expression of LPS-induced COX-2, iNOS, NF-κB, and MAPKs as well as production of prostaglandin E2(PGE2), nitric oxide (NO), IL-6, and TNF-αinduced by LPS. Our results demonstrate that PWS possesses anti-inflammatory activities via decreasing production of pro-inflammatory mediators through suppression of the signaling pathways of NF-κB and MAPKs in LPS-induced macrophage cells. More importantly, results of the carrageenan-(CA-) induced paw edema demonstrate an anti-edema effect of PWS. In addition, it is considered that PWS also inhibits the acute edematous inflammations through suppression of mast cell degranulations and inflammatory mediators, including COX-2, iNOS and TNF-α. Thus, our findings may provide scientific evidence to explain the anti-inflammatory properties of PWSin vitroandin vivo.

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Anti-Oxidative and Anti-Inflammatory Effects of Lobelia chinensis In Vitro and In Vivo

The American Journal of Chinese Medicine ◽

10.1142/s0192415x15500184 ◽

2015 ◽

Vol 43 (02) ◽

pp. 269-287 ◽

Cited By ~ 19

Author(s):

Kun-Cheng Li ◽

Yu-Ling Ho ◽

Guan-Jhong Huang ◽

Yuan-Shiun Chang

Keyword(s):

Nitric Oxide ◽

Folk Medicine ◽

Ethyl Acetate Fraction ◽

Raw264.7 Macrophages ◽

Tnf Α ◽

Cox 2 ◽

Anti Inflammatory ◽

Factor Α

Lobelia chinensis Lour (LcL) is a popular herb that has been widely used as folk medicine in China for the treatment of fever, lung cancer, and inflammation for hundreds of years. Recently, several studies have shown that the anti-inflammatory properties were correlated with the inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) from the NF-κB pathway. The aim of this study was to evaluate the anti-oxidative and anti-inflammatory activities of L. chinensis. Both suppressive activities on LPS-induced nitric oxide production in RAW264.7 macrophages in vitro and the acute rat lung injury model in vivo were studied. The results showed that the methanol extract of LcL and its fractions within the range of 62.5–250 μg/mL did not induce cytotoxicity (p < 0.001). The ethyl acetate fraction of LcL showed better NO inhibition activity than other fractions. On the other hand, the Lc-EA (62.5, 125, 250 mg/kg) pretreated rats showed a decrease in the pro-inflammatory cytokines (TNF-α, IL-β, IL-6) and inhibited iNOS, COX-2 expression through the NF-κB pathway. These results suggested that L. chinensis exhibited an anti-inflammatory effect through the NF-κB pathways.

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Synthesis of novel thiadiazole derivatives as selective COX-2 inhibitors

MedChemComm ◽

10.1039/c6md00367b ◽

2016 ◽

Vol 7 (12) ◽

pp. 2309-2327 ◽

Cited By ~ 10

Author(s):

Fatma A. Ragab ◽

Helmi I. Heiba ◽

Marwa G. El-Gazzar ◽

Sahar M. Abou-Seri ◽

Walaa A. El-Sabbagh ◽

...

Keyword(s):

Paw Oedema ◽

Analgesic Agents ◽

Thiadiazole Derivatives ◽

Cox 2 ◽

Anti Inflammatory ◽

Rat Paw ◽

Cox 2 Inhibitors ◽

Rat Paw Oedema

A novel series of thiadiazole derivatives were designed and synthesized for evaluation as selective COX-2 inhibitors in vitro and were investigated in vivo as anti-inflammatory and analgesic agents against carrageenan-induced rat paw oedema model in irradiated rats.

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