ArticleNature communications2025
Elucidation of the biosynthetic pathway of hydroxysafflor yellow A.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Emerging natural product development strategies drive the therapeutic potential exploration and clinical translation of hydroxysafflor yellow A.Journal of pharmaceutical analysis · 2026Review
- Metabolic Engineering Strategies for Flavonoid Biosynthesis in Saccharomyces cerevisiae: Current Advances and Future Perspectives.Biotechnology and bioengineering · 2026Review
- Hydroxysafflor Yellow A for Diabetic Retinopathy: A Critical Review of Retinal Neurovascular Mechanisms and Systemic-to-Ocular Pharmacokinetic Barriers.Antioxidants (Basel, Switzerland) · 2026Review
- Transcriptome Dynamics Reveal the Potential Roles of Long Non-Coding RNAs in Regulating Flower Color of Safflowers (International journal of molecular sciences · 2026Article
- BSA-seq integrated with transcriptomics and metabolomics revealing the candidate genes associated with safflower colors and flavonoid glycosides biosynthesis.Horticulture research · 2026Article
- Comprehensive characterization of safflower cytochrome P450 family and the role of CtCYP41 in flavonoid biosynthesis and drought response.BMC plant biology · 2026Article
- CtTLP13 Located in Extracellular Vesicles Enhances the Resistance of Safflower (Carthamus tinctorius) to Botrytis cinerea.Molecular plant pathology · 2026Article
- Gibberellic Acid-Induced Regulation of Antioxidant-Flavonoid Channels Provides Protection Against Oxidative Damage in Safflower Under Salinity Stress.Plants (Basel, Switzerland) · 2026Article
- Hydroxysafflor Yellow A improves diabetic nephropathy by inhibiting PI3K/AKT/mTOR pathway based on a multidimensional study.Frontiers in medicine · 2026Article
- CtChi19: a valuable gene for improving resistance to Botrytis cinerea and Alternaria alternata in Carthamus tinctorius.Frontiers in plant science · 2026Article
- Identification and Functional Analysis of Two UGT84 Glycosyltransferases in Flavonoid Biosynthesis ofPlants (Basel, Switzerland) · 2025Article
- Pharmacological actions and applications of safflower flavonoids.Frontiers in nutrition · 2025Review
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hydroxysafflor yellow A (HSYA) is a clinical investigational new drug for the treatment of acute ischemic stroke. It has a unique quinochalcone di-C-glycoside structure and is exclusively found in the flowers of safflower (Carthamus tinctorius). To date, little is known about the biosynthesis of HSYA. In this work, we characterize four key biosynthetic enzymes from C. tinctorius: CtF6H (6-hydroxylation of naringenin to produce carthamidin), CtCHI1 (isomerization between carthamidin and isocarthamidin), CtCGT (flavonoid di-C-glycosyltransferase), and Ct2OGD1 (2-oxoglutarate-dependent dioxygenase). Notably, Ct2OGD1 coordinates with CtCGT to convert carthamidin or isocarthamidin to HSYA. Functions of these genes are confirmed by VIGS (virus-induced gene silencing) in C. tinctorius, de novo biosynthesis of HSYA in Nicotiana benthamiana, semi-synthesis in yeast, and in vitro enzyme assays. We further find that the simultaneous presence and high expression of the above four key genes, together with the absence of F2H (flavanone 2-hydroxylase) genes, are essential for the biosynthesis of HSYA, and thus interpret mechanisms for the unique presence of HSYA in safflower. This work elucidates the biosynthetic pathway of HSYA and provides a foundation for the green and efficient production of this valuable medicinal natural product.
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