Table 1 Common inhibitors of lipid rafts with their mechanism
Drug | Mechanism | References |
|---|---|---|
Propofol | The propofol has a role for caveolae (specifically caveolin-1) in propofol-induced bronchodilatation. Due to its lipid nature, propofol may transiently disrupt caveolar regulation, thus altering ASM [Ca2+] and decreasing caveolin-1 expression | [57] |
Isoflurane | The isoflurane increases membrane fluidity and the permeability of the blood–brain barrier by distributing the highly ordered lipid domains with saturated lipids. It also weakened the sterol-phospholipid association in cholesterol-rich membranes | |
Pentobarbital | Pentobarbitals modify the physical characteristics of lipid rafts on model membranes and cause lipid membrane disorder of brain plasma membranes | [60] |
Lidocaine | Lidocaine is observed to distribute the erythrocyte membrane lipid rafts reversibly and abolish flotillin-1 in lipid rafts together with depleting cholesterol. In addition, the Lidocaine hydrochloride, an amphipathic local anaesthetic, is shown to reversibly disrupt rafts in erythrocyte membranes and alter the Gsα dependent signal transduction pathway. These findings provide evidence of rafts' presence while maintaining normal cholesterol content in erythrocyte membranes and confirm a role for raft-associated Gsα in signal transduction in erythrocytes | |
Tetracaine | Tetracaine induces lipid chain mobility, destabilizes the supported lipid bilayers, and induces lipid raft distribution and solubilization. Tetracaine causes a curvature change in the bilayer, which leads to the formation of the subsequent formation of up to 20-μm-long flexible lipid tubules as well as the formation of micron-size holes | [63] |
Dibucaine | Dibucaine hydrochloride has a distribution effect on lipid rafts. The inserting Dibucaine molecules into lipid bilayers induces a reduction in the ternary liposome's miscibility transition temperature (Tc) and a reduction in the phase boundary line tension. This suggests that the Dibucaine.HCl molecules may disturb ion channel functions by affecting the lipid bilayers surrounding the ion channels | [64] |
Bupivacaine | Bupivacaine stereostructure specifically interacts with membranes containing cholesterol, which is consistent with the clinical features of S (-)-bupivacaine. The bupivacaine interacted with liposomal membranes to increase membrane fluidity. They also revealed that the interactivity with lipid bilayer membranes is largely consistent with the local anaesthetic potency | [65] |
Dexmedetomidine Levomedetomidine Clonidine | Dexmedetomidine and clonidine acted on lipid bilayers to increase the membrane fluidity with potencies varying by a compositional difference of membrane lipids. Dexmedetomidine showed greater interactivity with neuro-mimetic and cardiomyocyte-mimetic membranes than clonidine, consistent with their comparative lipophilicity and activity. The effects of α2-adrenergic agonists on lipid raft model membranes were much weaker than those on other membranes, indicating that lipid rafts are not mechanistically relevant to them. Higher interactive dexmedetomidine was discriminated from lower interactive levomedetomidine in the presence of chiral cholesterol in membranes. An interactivity difference between the two enantiomers was largest in the superficial region of lipid bilayers, and the rank order of their membrane-interacting potency was reversed by replacing cholesterol with epicholesterol, suggesting that cholesterol’s 3β-hydroxyl groups positioned close to the membrane surface are responsible for the enantioselective interaction | [66] |
Morphine | Morphine increases the membrane fluidity of membranes | [67] |
Aspirin | It is observed that aspirin increases membrane fluidity, disrupts the membrane organization, and prevents raft formation | [64] |
Indomethacin Naproxen Ibuprofen | These compounds affected the organization of rat-like ordered lipid and protein membrane nanoclusters | [68] |
Edelfosine | It is observed that Edelfosine increases the fluidity of lipid rafts. Edelfosine is associated with cholesterol and colocalizes in vivo with rafts, causing the raft's structure modification | [69] |
Perifosine | It is observed that perifosine causes disrupted membrane raft domains | [70] |
Edelfosine Miltefosine | The edelfosine and miltefosine increase the fluidity of raft model membranes | [71] |
Erucylphosphocholine | Erucylphosphocholine is observed to increase the membrane raft fluidity and weaken the interaction between cholesterol and sphingomyelin | [72] |
2-Hydroxyoleic acid | 2-Hydroxyoleic acid increases the membrane raft fluidity | [73] |
Cisplatin | Cisplatin increases the membrane fluidity and induces apoptosis, which was inhibited by cholesterol (30 μg/mL) and monosialoganglioside-1 (80 μM) | |
Azithromycin | Azithromycin is observed to increase the fluidity of raft-like membranes | [76] |
Daunorubicin | Daunorubicin is observed to affect lipid rafts by decreasing the fluidity of raft-like membranes | [77] |
Doxorubicin | Doxorubicin is an anticancer drug that increases the fluidity of binary membranes but not ternary membranes | [78] |
Quercetin | Quercetin is observed to suppress the accumulation of lipid rafts to inhibit TNF-α production. In addition, it increases the fluidity of raft model membranes in mouse macrophages | |
Luteolin | Luteolin suppresses the accumulation of lipid rafts to inhibit TNF-α production in mouse macrophages | [80] |
EGCG | Epigallocatechin gallate (EGGG) decreases the fluidity of binary membranes. On the other hand, it induces lipid raft clustering and apoptotic cell death in human multiple myeloma cells | [81] |
Dimeric procyanidin | Dimeric procyanidin increases the membrane fluidity in human acute T-cell leukemia cells | [82] |
Hexameric procyanidin | Hexameric procyanidin decreases the membrane fluidity and prevents the lipid raft disruption induced by deoxycholate in human colon cancer cells | [83] |
Emodin | Emodin causes disrupted lipid rafts in human umbilical vein endothelial cells | [84] |
Ginsenosides | Ginsenosides increase the membrane fluidity and reduce the raft-marker protein concentration in lipid rafts in HeLa cells | [85] |
Saikosaponin | Saikosaponin inhibits Lipopolysaccharide-induced cytokine expression and Toll-like receptor localization in lipid rafts, and reduces membrane cholesterol levels in mouse macrophages | [86] |
Methyl-beta-cyclodextrin (MβCD) treatment | It is observed that MβCD causes depletion of cholesterol in the rafts by methyl-beta-cyclodextrin (MβCD) treatment impaired the expression of the cell surface receptor angiotensin-converting enzyme 2 (ACE2), resulting in a significant increase in SARS-CoV-2 entry into cells | [87] |
Statins | Statins reduces cholesterol synthesis by inhibiting the activity of HMG-CoA reductase. Statins could modulate virus entry, acting on the SARS‐CoV‐2 receptors, ACE2 and CD147, and/or lipid rafts engagement. In addition, statins, by inducing autophagy activation, could regulate virus replication or degradation, exerting protective effects | [88] |