Investigation of the anti-inflammatory effects of stigmasterol in mice: insight into its mechanism of action

Abstract

Stigmasterol is a phytosterol that presents pharmacologic properties. However, its anti-inflammatory mechanism and antinociceptive effect are not yet elucidated. Thus, the present study aimed to investigate the anti-inflammatory and antinociceptive activities of stigmasterol and its mechanism of action in mice. The antinociceptive activity was assessed by the acetic acid-induced writhing test, formalin test, and hot plate test. The anti-inflammatory activity was investigated by carrageenan-induced peritonitis and paw edema induced by arachidonic acid. The involvement of glucocorticoid receptors in the mechanism of stigmasterol anti-inflammatory action was investigated by molecular docking, also by pretreating mice with RU-486 (glucocorticoid receptor antagonist) in the acetic acid-induced writhing test. Mice motor coordination was evaluated by the rota-rod test and the locomotor activity by the open field test. The lowest effective dose of stigmasterol was standardized at 10 mg/kg (p.o.). It prevented abdominal writhes and paw licking, but it did not increase the latency time in the hot plate test, suggesting that stigmasterol does not show an antinociceptive effect in response to a thermal stimulus. Stigmasterol decreased leukocyte infiltration in peritonitis assay and reduced paw edema elicited by arachidonic acid. Molecular docking suggested that stigmasterol interacts with the glucocorticoid receptor. Also, RU-486 prevented the effect of stigmasterol in the acetic-acid abdominal writhing test, which might indicate the contribution of glucocorticoid receptors in the mechanism of stigmasterol action. Stigmasterol reduced the number of crossings but did not impair mice's motor coordination. Our results show that stigmasterol presents anti-inflammatory effects probably mediated by glucocorticoid receptors.

Health Benefits and Pharmacological Properties of Stigmasterol

“…Recently, Morgan et al [ 51 ] aimed to investigate the anti-inflammatory properties of stigmasterol in mice and its underlying mechanism of action using carrageenan-induced peritonitis and arachidonic acid-induced paw edema. Therefore, stigmasterol exhibited potent anti-inflammatory action, by decreasing arachidonic acid-induced paw edema and the leukocyte infiltration in the peritonitis test.…”

“…In fact, this bioactive sterol extracted from different natural sources plays an important anti-inflammatory and analgesic role [ 48 ]. The anti-inflammatory properties of stigmasterol were assessed in vivo, and the underlying mechanism of action was demonstrated by molecular docking analysis [ 49 , 50 , 51 , 52 ].…”

The Genus Alternanthera: Phytochemical and Ethnopharmacological Perspectives

“…Pelisoli Formagio and the team had observed the significant decrease in the polymorphonuclear cells as well as increase in the mononuclear cells in rat’s exudate after treated with the aqueous extract, while P Shivashankar and the team found the reduction in the colon weight in acetic acid-induced colitis model of adult Wistar albino rats after treatment with the methanolic extract ( Pelisoli Formagio et al, 2012 ; P et al, 2016 ). Phytomolecules like kaempferol ( Devi et al, 2015 ), quercetin ( Lesjak et al, 2018 ), stigmasterol ( Morgan et al, 2021 ), p-coumaric acid ( Pragasam et al, 2012 ), ferulic acid ( Ozaki, 1992 ), and chlorogenic acid ( Hwang et al, 2013 ) may be responsible for the anti-inflammatory potential of Alternanthera brasiliana (L.) Kuntze.…”

“…ex DC., including but not limited to cyclooxygenase -1 and -2 inhibition ( Biella et al, 2008 ), modulating NF- κB pathway ( Muniandy et al, 2018a ), leukocyte migration ( Kassuya et al, 2021 ), etc. Phytomolecules like kaempferol ( Devi et al, 2015 ; Pizzo et al, 2018 ), quercetin ( Lesjak et al, 2018 ), vitexin ( Rosa et al, 2016 ), stigmasterol ( Morgan et al, 2021 ), β-sitosterol ( Loizou et al, 2010 ), 4-hydroxybenzoic acid ( Winter et al, 2017 ), ellagic acid ( Corbett et al, 2010 ), ferulic acid ( Ozaki, 1992 ), campesterol ( Moreno-Anzúrez et al, 2017 ), spinasterol ( Jeong et al, 2010 ), β-carotene ( Uteshev et al, 2000 ), p-coumaric acid ( Pragasam et al, 2012 ), ricinoleic acid ( Vieira et al, 2001 ), and chlorogenic acid ( Hwang et al, 2013 ) may be responsible for the anti-inflammatory potential of Alternanthera sessilis (L.) R.Br. ex DC.…”

Network Pharmacology and ­Experimental Analyses of the Mechanism of Analgesic and Glucose Intolerance Through Glucocorticoid Signaling in C57 Mice Treated with Water Extract of Prunella vulgaris L. Spica

“…17 Similarly, rosmarinic acid, a featured compound in plants of the Labiatae, is able to attenuate repetitive viral infection stress through up-regulation of the GC receptor (GR). 18,19 In addition, stigmasterol in P. vulgaris may be able to interact with the GR playing anti-inflammatory effect, 20 but the effects and mechanisms are not fully clarified.…”