Possible Interaction: Melatonin and Sirolimus

“Our data further indicated that melatonin administration reduced rapamycin‐associated toxicity to healthy cells.”

“Our results demonstrated that combined treatment with rapamycin and melatonin blocked the negative feedback loop from the specific downstream effector of mTOR activation S6K1 to Akt signalling, which decreased cell viability, proliferation and clonogenic capacity.”

“Overall, our findings suggested that melatonin could be used as an adjuvant agent with rapamycin , improving effectiveness while minimizing its side effects.”

“We further examined the potential synergistic effects of melatonin with rapamycin in Cal‐27 xenograft mice.”

“Cotreatment with melatonin and rapamycin , an autophagy inducer, had an additive effect on mutant‐TGFBIp clearance compared to treatment with either drug alone.”

“Pretreatment of LY294002 (a PI3K inhibitor) or rapamycin (an mTOR inhibitor) markedly reduced EGF‐induced motility and p‐AKT/p‐mTOR/c‐Jun/Sp1 expression when combined with melatonin.”

“Lastly, MLT treatment significantly decreased the levels of toll-like receptors 4 (TLR4), phosphorylated-protein kinase B (Akt), and phosphorylated-mechanistic target of rapamycin (mTOR), indicating that blocking TLR4/Akt/mTOR pathway might be an underlying basis for the anti-inflammatory and anti-apoptosis effects of MLT.”

“Lastly, MLT treatment significantly decreased the levels of toll‐like receptors 4 (TLR4), phosphorylated‐protein kinase B (Akt), and phosphorylated‐mechanistic target of rapamycin (mTOR), indicating that blocking TLR4/Akt/mTOR pathway might be an underlying basis for the anti‐inflammatory and anti‐apoptosis effects of MLT.”

“The results of maintaining bone mass and bone strength with RAP plus MEL administration were evaluated by histology, microcomputerized tomography (Micro-CT), gene expression analysis and biomechanical testing.”

“These results seemed to indicate that RAP could increase the effects of MEL on age-dependent bone loss.”

“However, the AMPK activator AICAR and the mTOR inhibitor rapamycin reduced the protective effects of melatonin on IRI.”

“Pretreatment of Rapa reversed the effect of MLT on autophagic flux as well as mTOR pathway.”

“Moreover, melatonin inhibits the phosphorylation of the mammalian target of the rapamycin (mTOR) and Akt.”

“Immunosuppressive maintenance therapy with CsA and RPM modulated early melatonin secretion, indicating a specific secondary action of these drugs.”

“In contrast, treatment with RPM significantly decreased the melatonin peak post‐Tx up to day 7 (87 ± 25.2 pg/mL; P < 0.001), compared with naïve animals (155 ± 25.8 pg/mL).”

“Drugs like melatonin and metformin exhibited shared targets with rapamycin in the human PPIN.”