Syringol isolated from Eleusine coracana (L.) Gaertn bran suppresses inflammatory response through the down-regulation of cPLA2, COX-2, IκBα, p38 and MPO signaling in sPLA2 induced mice paw oedema

Gowda, Mallanayakanakatte D. Milan; Jayachandra, Krishnegowda; Joshi, Vikram; Manjuprasanna, Vaddarahally N.; Rudresha, Gotravalli V.; Velmurugan, D.; Pachaiappan, Raman; Jameel, Noor Mohamed; Vishwanath, Bannikuppe S.

doi:10.1007/s10787-022-00983-3

Cited by 4 publications

(1 citation statement)

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“…sPLA 2 activity assay was carried out in 96‐well plate assay according to Milan Gowda et al 15 with slight modifications. The standard assay mixture contained 200 µl of buffer (10 mM Tris‐HCl, 10 mM CaCl 2 , 100 mM NaCl, pH 7.8), 25 µg of sPLA 2 s (HSF‐PLA 2 , HPF‐PLA 2 , and NN‐PLA 2 ) followed by the addition of 50 mM of substrate (4‐nitro‐3‐octanoyloxy‐benzoic acid) to a final volume of 260 µl, then the reaction mixture was incubated for up to 40 min at 37°C and the absorbance was taken at 425 nm with 10 min time interval.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of sPLA₂ enzyme activity by cell‐permeable antioxidant EUK‐8 and downregulation of p38, Akt, and p65 signals induced by sPLA₂ in inflammatory mouse paw edema model

Jayachandra

Gowda

Rudresha

et al. 2022

J of Cellular Biochemistry

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The arachidonic acid (AA) metabolic pathway, plays a vital role in the production of eicosanoids by the action of pro-inflammatory secretory phospholipase A 2 (PLA 2 ). Release of eicosanoids is known to be involved in many inflammatory diseases. Identification of the inhibitory molecules of this AA pathway enzyme along with the regulation of intracellular signaling cascades may be a finer choice to develop as a powerful anti-inflammatory drug. In this regard, we have screened few cell-permeable antioxidant molecules Tempo, Mito-TEMPO, N,N'-Bis (salicylideneamino)ethane-manganese(II) (EUK)-134, and EUK-8 against proinflammatory sPLA 2 s. Among these, we found EUK-8 is a potent inhibitor with its IC 50 value ranges 0.7-2.0 µM for sPLA 2 s isolated from different sources.Furthermore, docking studies confirm the strong binding of EUK-8 towards sPLA 2 . In vivo effect of EUK-8 was studied in HSF-sPLA 2 -induced edema in mouse paw model. In addition to neutralizing the edema, EUK-8 significantly reduces the phosphorylation level of inflammatory proteins such as p38 member of MAPK pathway, Akt, and p65 along with the suppression of pro-inflammatory cytokine (interleukin-6) and chemokine (CXCL1) in edematous tissue. This shows that EUK-8 not only inhibits the sPLA 2 activity, it also plays an important role in the regulation of sPLA 2 -induced cell signaling cascades. Apart from the sPLA 2 inhibition, we also examine the regulatory actions of EUK-8 with other downstream enzymes of AA pathway such as 5-LOX assay in human polymorphonuclear leukocytes (PMNs) and COX-2 expression in carrageenan-λ induced paw edema. Here EUK-8 significantly inhibits 5-LOX enzyme activity and downregulates COX-2 expression. These data indicate that EUK-8 found to

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Section: Methodsmentioning

confidence: 99%

Inhibition of sPLA₂ enzyme activity by cell‐permeable antioxidant EUK‐8 and downregulation of p38, Akt, and p65 signals induced by sPLA₂ in inflammatory mouse paw edema model

Jayachandra

Gowda

Rudresha

et al. 2022

J of Cellular Biochemistry

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GC–MS analysis, HPLC–UV analysis, antimicrobial and antioxidant activities of extracts of wild-growing anabasis salsa native to kazakhstan desert iands

Datkhayev,

Shegebayev,

Turgumbayeva

et al. 2024

Phytochem Rev

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Protective Effects of Hemp (Cannabis sativa) Root Extracts against Insulin-Deficient Diabetes Mellitus In Mice

Kim

Kim³

et al. 2023

Molecules

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The pharmacological potential of industrial hemp (Cannabis sativa) has been widely studied. However, the majority of studies have focused on cannabidiol, isolated from the inflorescence and leaf of the plant. In the present study, we evaluated the anti-diabetic potential of hemp root water (HWE) and ethanol extracts (HEE) in streptozotocin (STZ)-induced insulin-deficient diabetic mice. The administration of HWE and HEE ameliorated hyperglycemia and improved glucose homeostasis and islet function in STZ-treated mice (p < 0.05). HWE and HEE suppressed β-cell apoptosis and cytokine-induced inflammatory signaling in the pancreas (p < 0.05). Moreover, HWE and HEE normalized insulin-signaling defects in skeletal muscles and apoptotic response in the liver and kidney induced by STZ (p < 0.05). Gas chromatography-mass spectrometry analysis of HWE and HEE showed possible active compounds which might be responsible for the observed anti-diabetic potential. These findings indicate the possible mechanisms by which hemp root extracts protect mice against insulin-deficient diabetes, and support the need for further studies geared towards the application of hemp root as a novel bioactive material.

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Syringol isolated from Eleusine coracana (L.) Gaertn bran suppresses inflammatory response through the down-regulation of cPLA2, COX-2, IκBα, p38 and MPO signaling in sPLA2 induced mice paw oedema

Cited by 4 publications

References 65 publications

Inhibition of sPLA₂ enzyme activity by cell‐permeable antioxidant EUK‐8 and downregulation of p38, Akt, and p65 signals induced by sPLA₂ in inflammatory mouse paw edema model

Inhibition of sPLA₂ enzyme activity by cell‐permeable antioxidant EUK‐8 and downregulation of p38, Akt, and p65 signals induced by sPLA₂ in inflammatory mouse paw edema model

GC–MS analysis, HPLC–UV analysis, antimicrobial and antioxidant activities of extracts of wild-growing anabasis salsa native to kazakhstan desert iands

Protective Effects of Hemp (Cannabis sativa) Root Extracts against Insulin-Deficient Diabetes Mellitus In Mice

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Syringol isolated from Eleusine coracana (L.) Gaertn bran suppresses inflammatory response through the down-regulation of cPLA2, COX-2, IκBα, p38 and MPO signaling in sPLA2 induced mice paw oedema

Cited by 4 publications

References 65 publications

Inhibition of sPLA2 enzyme activity by cell‐permeable antioxidant EUK‐8 and downregulation of p38, Akt, and p65 signals induced by sPLA2 in inflammatory mouse paw edema model

Inhibition of sPLA2 enzyme activity by cell‐permeable antioxidant EUK‐8 and downregulation of p38, Akt, and p65 signals induced by sPLA2 in inflammatory mouse paw edema model

GC–MS analysis, HPLC–UV analysis, antimicrobial and antioxidant activities of extracts of wild-growing anabasis salsa native to kazakhstan desert iands

Protective Effects of Hemp (Cannabis sativa) Root Extracts against Insulin-Deficient Diabetes Mellitus In Mice

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Inhibition of sPLA₂ enzyme activity by cell‐permeable antioxidant EUK‐8 and downregulation of p38, Akt, and p65 signals induced by sPLA₂ in inflammatory mouse paw edema model

Inhibition of sPLA₂ enzyme activity by cell‐permeable antioxidant EUK‐8 and downregulation of p38, Akt, and p65 signals induced by sPLA₂ in inflammatory mouse paw edema model