Organ- and species-specific biological activity of rosmarinic acid

Iswandana, Raditya; Pham, Bao Tung; Haaften, Wouter T. van; Luangmonkong, Theerut; Oosterhuis, Dorenda; Mutsaers, Henricus A M; Olinga, Peter

doi:10.1016/j.tiv.2016.01.009

Cited by 30 publications

(15 citation statements)

References 30 publications

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“…As illustrated in our human ex vivo study, galunisertib is a promising drug to be further investigated for the treatment of human liver fibrosis. Although, species‐specific biological activity of compounds is widespread and a major hurdle in the development of effective therapeutics (Iswandana et al, ; Westra et al, ), encouragingly, galunisertib exhibited its antifibrotic effects not only in rodent but also in humans PCLS. The inhibition of SMAD2 phosphorylation is probably the main mechanism underlying the antifibrotic effect of galunisertib.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the antifibrotic potency of galunisertib in a human ex vivo model of liver fibrosis

Luangmonkong

Suriguga

Bigaeva

et al. 2017

British J Pharmacology

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Section: Discussionmentioning

confidence: 99%

Evaluating the antifibrotic potency of galunisertib in a human ex vivo model of liver fibrosis

Luangmonkong

Suriguga

Bigaeva

et al. 2017

British J Pharmacology

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“…An increasing number of plant sources have been screened for RA content 7–9 , and biotechnological and metabolic engineering approaches for RA production have been studied in previous reports 10–15 . However, plant sources have remained insufficient in meeting the rising demand of RA in recent years.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic analyses reveal biosynthetic genes related to rosmarinic acid in Dracocephalum tanguticum

Sun

et al. 2017

Sci Rep

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Dracocephalum tanguticum Maxim, a Lamiaceae species endemic to the Qinghai-Tibetan Plateau and adjacent regions, is an important ornamental, medicinal and aromatic herb. In this study, a comprehensive transcriptome of 18 libraries from six organs namely, roots, stems, leaves, sepals, flowers and seeds of D. tanguticum were generated. More than 100 Gb of sequence data were obtained and assembled de novo into 187,447 transcripts, including 151,463 unigenes, among which the six organs shared 17.7% (26,841). In addition, all unigenes were assigned to 362 pathways, in which 'biosynthesis of secondary metabolites' is the second enriched pathway. Furthermore, rosmarinic acid (RA) is one of the multifunctional phenolic bioactive compounds produced in some Lamiaceae species. The six organs of D. tanguticum were confirmed to produce RA. A total of 22 predicted biosynthetic genes related to RA from the transcriptome were further isolated. Two of these genes were identified as candidates by evaluating the correlation coefficient between the RA contents and the expression of the predicted biosynthetic genes in the six organs. The new sequence information will improve the knowledge of D. tanguticum, as well as provide a reference tool for future studies of biosynthetic genes related to RA in this species.Dracocephalum tanguticum Maxim, a Lamiaceae species endemic to the Qinghai-Tibetan Plateau (QTP) and adjacent regions, is an important ornamental, medicinal and aromatic herb. This plant is one of the important traditional Tibetan medicines which have been used by locals for a long time. However, no study has been reported on D. tanguticum because of the plant's limited distribution. The high-altitude QTP region has unique climate factors, including low oxygen levels, intense ultraviolet light, and large temperature difference between day and night, as well as prolonged daytime during the short growing seasons, which usually commences on April and ends in October for D. tanguticum. All of these harsh factors may be beneficial for the biosynthesis of protective secondary metabolites in D. tanguticum.Rosmarinic acid (RA) is a multifunctional phenolic bioactive compound that possesses astringent, antimutagen, antibacterial, antiviral, antifungal, anti-inflammatory and anti-oxidative activities [1][2][3][4][5][6] . An increasing number of plant sources have been screened for RA content 7-9 , and biotechnological and metabolic engineering approaches for RA production have been studied in previous reports [10][11][12][13][14][15] . However, plant sources have remained insufficient in meeting the rising demand of RA in recent years.Previous literature reported that the amino acids, L-phenylalanine and L-tyrosine, are the two precursors of the RA biosynthetic pathway in Coleus blumei, a Lamiaceae species 16 . In the phenylalanine-derived pathway of RA biosynthesis, phenylalanine ammonia-lyase (PAL) catalyses the oxidative desamination of phenylalanine, forming t-cinnamic acid, and cinnamic acid; 4-hydroxylase (C4H) introduces the par...

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“…The rootcause of this inflammatory response in slices is not fully understood, though it probably results from mechanical (e.g., slicing procedure itself) and chemical injury (e.g., warm/cold ischemia) which can lead to a wound-repair response [27]. Previous literature reported similar responses in precision-cut intestinal slices (PCIS) prepared from rat, mouse, and human tissue [28]. Furthermore, PCKS prepared from human tissue have also been characterized by inflammation upon incubation for up to 48 h [8].…”

Section: Slice Inflammationmentioning

confidence: 99%

siRNA-Mediated RNA Interference in Precision-Cut Tissue Slices Prepared from Mouse Lung and Kidney

Ruigrok

Maggan

Willaert

et al. 2017

AAPS J

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Abstract.Small interfering RNA (siRNA)-mediated RNAi interference (RNAi) is a powerful post-transcriptional gene silencing mechanism which can be used to study the function of genes in vitro (cell cultures) and in vivo (animal models). However, there is a translational gap between these models. Hence, there is a need for novel experimental models that combine the advantages of in vitro and in vivo models (e.g., simplicity, flexibility, throughput, and representability) to study the effects of siRNA. This need may be addressed by precision-cut tissue slices (PCTS), which represent an ex vivo model that mimics the structural and functional characteristics of a whole organ. The goal of this study was to investigate whether self-deliverable siRNA (Accell siRNA) can be used in precision-cut lung slices (PCLuS) and precision-cut kidney slices (PCKS) to achieve RNAi ex vivo. PCLuS and PCKS were prepared from mouse tissue, and they were subsequently incubated up to 48 h with no siRNA (untransfected), non-targeting Accell siRNA, or Gapdhtargeting Accell siRNA. Significant Gapdh mRNA silencing was achieved (PCLuS~55%; PCKS 40%) without compromising the viability and morphology of slices. Fluorescence microscopy confirmed that Accell siRNA diffused into PCLuS and PCKS. Spontaneous inflammation upon incubation was observed in PCLuS and PCKS as shown by a higher mRNA expression of proinflammatory cytokines Il1b, Il6, and Tnfa, although Accell siRNA appeared to diminish this response in PCLuS after 24 h. In conclusion, this ex vivo transfection model can be used to evaluate the effects of siRNA in relevant biological environments.

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Organ- and species-specific biological activity of rosmarinic acid

Cited by 30 publications

References 30 publications

Evaluating the antifibrotic potency of galunisertib in a human ex vivo model of liver fibrosis

Evaluating the antifibrotic potency of galunisertib in a human ex vivo model of liver fibrosis

Transcriptomic analyses reveal biosynthetic genes related to rosmarinic acid in Dracocephalum tanguticum

siRNA-Mediated RNA Interference in Precision-Cut Tissue Slices Prepared from Mouse Lung and Kidney

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