β-Sitosterol Attenuates the Intracranial Aneurysm Growth by Suppressing TNF-α-Mediated Mechanism

Abstract

Background: Onset of inflammation associated with increased extracellular matrix degradation of vascular walls in the neuronal area is the pathophysiology of cerebral aneurysms. It has been documented well that β-sitosterol has protective effects on various brain-related diseases independent of their lipid-lowering effects; the current work was framed to examine the effect of β-sitosterol on CA progression. Materials and Methods: To study whether β-sitosterol has a suppressive effect on the growth of CA, β-sitosterol administration started prior to aneurysm induction. CA was induced in Wistar male rats with or without oral administration of β-sitosterol. The expression of chemokines and inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-8, IL-1β, IL-17, IL-6, matrix metalloproteinases (MMP)-2 and -9, was elucidated by ELISA and RT-PCR. Results: Rats treated with β-sitosterol exhibited a significant reduction in aneurysmal size compared with control rats. In addition, β-sitosterol administration reduced the expression of chemokines and inflammatory cytokines, while gelatin zymography data revealed declined activity of MMP-2 and -9 in aneurismal walls. Furthermore, the levels of cytokines were significantly reduced in β-sitosterol-administered rats compared to CA rats. Conclusions: Treatment with β-sitosterol suppresses the development of CA by inhibiting inflammatory reactions including TNF-α and thus β-sitosterol can be a suggestive candidate for the prevention of CA treatment and progression.

Identifying Active Compounds and Targets of Fritillariae thunbergii against Influenza-Associated Inflammation by Network Pharmacology Analysis and Molecular Docking

“…BS was reported to suppress the chemotactic cytokine genes in cystic fibrosis bronchial epithelial cells [22] and inhibit epithelial-to-mesenchymal transition in lung alveolar cells, consistent with our GO and KEGG results [23]. Recent pathophysiology-associated studies showed that BS attenuates rheumatoid inflammation in mice via modulating macrophages [24], and reduced expression of inflammatory cytokines and TNFα in brain inflammation-induced Wistar rats [25]. PG is an anthocyanidin that is flavylium-substituted by hydroxy groups at positions three, five, seven and four, which is actually the sole chemical species in fairly acidic aqueous solution [26].…”

Network pharmacology-based active compounds and pharmacological mechanisms of ginseng for depression in post-COVID-19

“…It has been reported that β-sitosterol has protective effects on various brain-related diseases independent of their lipid-lowering effects. β-sitosterol can also suppress the development of cerebral aneurysm by inhibiting in ammatory reactions including TNF-α [21]. This indicated that our prediction of the active ingredient in ginseng that plays an antidepressant role is reasonable.…”

Potential Molecular Mechanisms of Plantain in the Treatment of Gout and Hyperuricemia Based on Network Pharmacology

“…Plantain can reduce serum uric acid level of hyperuricemia mice by inhibiting XOD activity and can improve swelling and activity of gouty arthritis [ 39 – 41 ]. Studies have shown that the compounds baicalein [ 42 ], baicalin [ 35 ], sitosterol [ 43 ], stigmasterol [ 44 ], and luteolin [ 45 ] can inhibit the level of IL-17. In conclusion, plantain has a good therapeutic effect on gouty arthritis and hyperuricemia; however, the mechanism of plantain in the treatment of gouty arthritis and hyperuricemia disease through IL-17 signaling pathway needs to be further explored.…”

“…Sitosterol can treat cerebral aneurysms by reducing the expression of chemokines and inflammatory cytokines TNF- α , IL-8, IL-1 β , IL-17, IL-6, and MMP-2/9 [ 43 ]. It can reduce the level of IL-17, TNF- α , IL-1 β , IL-6, and IL-12 in RA mice and promote the production of anti-inflammatory cytokine IL-10 [ 44 , 74 ].…”