Anti-Inflammatory Activity of Oxyresveratrol Tetraacetate, an Ester Prodrug of Oxyresveratrol, on Lipopolysaccharide-Stimulated RAW264.7 Macrophage Cells

Thaweesest, Wuttinont; Buranasudja, Visarut; Phumsuay, Rianthong; Muangnoi, Chawanphat; Vajragupta, Opa; Sritularak, Boonchoo; Rashatasakhon, Paitoon; Rojsitthisak, Pornchai

doi:10.3390/molecules27123922

Cited by 3 publications

(1 citation statement)

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“…With a considerable repertoire of pharmacological applications, Morus alba is now the most studied species for oxyresveratrol production (Lim et al, 2015). OxyR presents strong tyrosinase inhibitory activity (J.-K. Kim et al, 2012), together with anti-inflammatory (Thaweesest et al, 2022) and antioxidant (Heo et al, 2016) effects. Its protective properties against neurological diseases have also been reported (Ban et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Biosynthesis of oxyresveratrol in mulberry (Morus albaL.) is mediated by a group of p-coumaroyl-CoA 2’-hydroxylases acting upstream of stilbene synthases

Santiago,

Romero,

Martínez

et al. 2024

Preprint

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Mulberry (Morus alba L.) is considered a millenary medicinal plant and a food source for silkworms. Different M. alba extracts offer a variety of biological and pharmacological properties that are in part attributed to stilbenoids, a small group of phenylpropanoids that include resveratrol and oxyresveratrol. These are naturally present in non-renewable parts of mulberry trees, impeding their efficient extraction. As a way to bypass this spatiotemporal restriction, we generated cell suspensions from mulberry twigs and demonstrated that the combined use of methyl jasmonate and methyl- or hydroxypropyl-β-cyclodextrins elicited a high production of resveratrol and oxyresveratrol, both intra and extracellularly. To identify oxyresveratrol-producing enzymes (unknown to date), we first improved the structural and functional annotation of the mulberry genome by integrating short and long-read sequencing data. We further combined this data with transcriptome, metabolite and proteome time-series evidence to identify a complete set of elicited phenylpropanoid- and stilbenoid-related genes. These included 22 stilbene synthase (STS) genes and a group of six p-coumaroyl-CoA 2-hydroxylases (C2Hs) that were highly co-expressed with resveratrol and oxyresveratrol accumulation. We transiently transformed Nicotiana benthamiana plants and grapevine (Vitis vinifera L.) cell suspensions to functionally validate the role of C2Hs as the first committed step of oxyresveratrol synthesis, providing an alternative substrate for STSs by hydroxylating p-coumaroyl-coA into 2,4-dihydroxycinnamoyl-CoA. We offer tools for genomic and transcriptomic exploration in the context of jasmonate elicitation aiding in the characterization of novel stilbenoid-modifying and regulatory genes in the Morus genus.

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