Antiallergic activity of rosmarinic acid esters is modulated by hydrophobicity, and bulkiness of alkyl side chain

Zhu, Fengxian; Xu, Zhongming; Yonekura, Lina; Yang, Ronghua

doi:10.1080/09168451.2015.1010478

Cited by 20 publications

(15 citation statements)

References 22 publications

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“…Additionally, here we evaluated the anti-tumor effects and mechanisms of action of RAME that were not observed after RA treatment (Additional file 1: Figure S6). Interestingly, there are several medicinal chemistry data demonstrating that the length of the alkyl side chain determines the bioactivity of RA derivatives [52–54]. According to our virtual screening data in Fig.…”

Section: Discussionmentioning

confidence: 71%

“…Rosmarinic acid (RA) is a natural polyphenolic substance found in various Lamiaceae herbs such as perilla [43], rosemary [44], sage [45], mint [46], basil [47], and thyme [48]. A number of studies have reported the biological effects of RA and one of its derivatives RAME, including anti-inflammatory [49, 50], anti-allergic [51, 52], and anti-microbial [53] effects. Additionally, here we evaluated the anti-tumor effects and mechanisms of action of RAME that were not observed after RA treatment (Additional file 1: Figure S6).…”

Section: Discussionmentioning

confidence: 99%

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Identification of a novel S6K1 inhibitor, rosmarinic acid methyl ester, for treating cisplatin-resistant cervical cancer

Nam

et al. 2019

BMC Cancer

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Background The mTOR/S6K1 signaling pathway is often activated in cervical cancer, and thus considered a molecular target for cervical cancer therapies. Inhibiting mTOR is cytotoxic to cervical cancer cells and creates a synergistic anti-tumor effect with conventional chemotherapy agents. In this study, we identified a novel S6K1 inhibitor, rosmarinic acid methyl ester (RAME) for the use of therapeutic agent against cervical cancer. Methods Combined structure- and ligand-based virtual screening was employed to identify novel S6K1 inhibitors among the in house natural product library. In vitro kinase assay and immunoblot assay was used to examine the effects of RAME on S6K1 signaling pathway. Lipidation of LC3 and mRNA levels of ATG genes were observed to investigate RAME-mediated autophagy. PARP cleavage, mRNA levels of apoptotic genes, and cell survival was measured to examine RAME-mediated apoptosis. Results RAME was identified as a novel S6K1 inhibitor through the virtual screening. RAME, not rosmarinic acid, effectively reduced mTOR-mediated S6K1 activation and the kinase activity of S6K1 by blocking the interaction between S6K1 and mTOR. Treatment of cervical cancer cells with RAME promoted autophagy and apoptosis, decreasing cell survival rate. Furthermore, we observed that combination treatment with RAME and cisplatin greatly enhanced the anti-tumor effect in cisplatin-resistant cervical cancer cells, which was likely due to mTOR/S6K1 inhibition-mediated autophagy and apoptosis. Conclusions Our findings suggest that inhibition of S6K1 by RAME can induce autophagy and apoptosis in cervical cancer cells, and provide a potential option for cervical cancer treatment, particularly when combined with cisplatin. Electronic supplementary material The online version of this article (10.1186/s12885-019-5997-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Identification of a novel S6K1 inhibitor, rosmarinic acid methyl ester, for treating cisplatin-resistant cervical cancer

Nam

et al. 2019

BMC Cancer

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“…We observe that modification of the n-propyl radical ( 3 ) to isopropyl ( 4 ) contributes to a reduction in activity, possibly due to the volume of the isopropyl group that compound 4 presents in its branch. Propyl p -coumarate ( 3 ) was twice as potent as 2-methoxyethyl p -coumarate ( 5 ) [42,43]. Compound 3 also presented greater selectivity than compound 5 for the epimastigote form (SI = 26.55, SI ≥ 14.05, respectively), and the trypomastigote form (SI = 3.8, SI ≥ 1.25, respectively).…”

Section: Resultsmentioning

confidence: 99%

Trypanocidal Mechanism of Action and in silico Studies of p-Coumaric Acid Derivatives

Lopes

Castillo

Monteiro

et al. 2019

IJMS

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Trypanosoma species are responsible for chronic and systemic infections in millions of people around the world, compromising life quality, and family and government budgets. This group of diseases is classified as neglected and causes thousands of deaths each year. In the present study, the trypanocidal effect of a set of 12 ester derivatives of the p-coumaric acid was tested. Of the test derivatives, pentyl p-coumarate (7) (5.16 ± 1.28 μM; 61.63 ± 28.59 μM) presented the best respective trypanocidal activities against both epimastigote and trypomastigote forms. Flow cytometry analysis revealed an increase in the percentage of 7-AAD labeled cells, an increase in reactive oxygen species, and a loss of mitochondrial membrane potential; indicating cell death by necrosis. This mechanism was confirmed by scanning electron microscopy, noting the loss of cellular integrity. Molecular docking data indicated that of the chemical compounds tested, compound 7 potentially acts through two mechanisms of action, whether by links with aldo-keto reductases (AKR) or by comprising cruzain (CZ) which is one of the key Trypanosoma cruzi development enzymes. The results indicate that for both enzymes, van der Waals interactions between ligand and receptors favor binding and hydrophobic interactions with the phenolic and aliphatic parts of the ligand. The study demonstrates that p-coumarate derivatives are promising molecules for developing new prototypes with antiprotozoal activity.

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“…Rosmarinic acid methyl ester (RAME), a derivative of rosmarinic acid (RA), has several biological effects, such as anti-microbial, anti-inflammatory, and anti-allergic effects [ 16 , 17 , 18 ]. RAME also exhibits anti-oxidant and anti-melanogenesis in vivo [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Rosmarinic Acid Methyl Ester Regulates Ovarian Cancer Cell Migration and Reverses Cisplatin Resistance by Inhibiting the Expression of Forkhead Box M1

et al. 2020

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Rosmarinic acid methyl ester (RAME), a derivative of rosmarinic acid (RA), is reported to have several therapeutic effects, including anti-tumor effects against cervical cancer. However, its anti-tumor effects in ovarian cancer is unclear. In this study, we studied the molecular pathways associated with the anti-tumor effects of RAME in ovarian cancer. To identify the effects of RAME in ovarian cancer, RNA sequencing was performed in RAME-treated ovarian cancer cells; we found that RAME treatment downregulated the genes closely involved with the target genes of the transcription factor Forkhead box M1 (FOXM1). It was reported that FOXM1 is overexpressed in a variety of cancer cells and is associated with cell proliferation and tumorigenesis. Therefore, we hypothesized that FOXM1 is a key target of RAME; this could result in its anti-tumor effects. Treatment of ovarian cancer cells with RAME-inhibited cell migration and invasion, as shown by wound healing and transwell migration assays. To examine whether RAME represses the action of FOXM1, we performed quantitative RT-PCR and ChIP-qPCR. Treatment of ovarian cancer cells with RAME decreased the mRNA expression of FOXM1 target genes and the binding of FOXM1 to its target genes. Moreover, FOXM1 expression was increased in cisplatin-resistant ovarian cancer cells, and combination treatment with RAME and cisplatin sensitized the cisplatin-resistant ovarian cancer cells, which was likely due to FOXM1 inhibition. Our research suggests that RAME is a promising option in treating ovarian cancer patients, as it revealed a novel molecular pathway underlying its anti-tumor effects.

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Antiallergic activity of rosmarinic acid esters is modulated by hydrophobicity, and bulkiness of alkyl side chain

Cited by 20 publications

References 22 publications

Identification of a novel S6K1 inhibitor, rosmarinic acid methyl ester, for treating cisplatin-resistant cervical cancer

Identification of a novel S6K1 inhibitor, rosmarinic acid methyl ester, for treating cisplatin-resistant cervical cancer

Trypanocidal Mechanism of Action and in silico Studies of p-Coumaric Acid Derivatives

Rosmarinic Acid Methyl Ester Regulates Ovarian Cancer Cell Migration and Reverses Cisplatin Resistance by Inhibiting the Expression of Forkhead Box M1

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