Demystifying traditional herbal medicine with modern approach

Li, Fu‐Shuang; Weng, Jing-Ke

doi:10.1038/nplants.2017.109

Cited by 345 publications

(237 citation statements)

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“…lyciumins | BURP domain | ribosomal peptides | natural products | plant metabolism P lants have been an important source of traditional medicines in many cultures for millennia. Underlying the historic use of medicinal plants are bioactive natural products produced in these organisms for signaling and defense (1). Most plant natural products with potential pharmacological applications were discovered based on their bioactivity in bioprospecting studies inspired by traditional herbal medicines (2).…”

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confidence: 99%

Gene-guided discovery and engineering of branched cyclic peptides in plants

Kersten

Weng

2018

Proc. Natl. Acad. Sci. U.S.A.

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The plant kingdom contains vastly untapped natural product chemistry, which has been traditionally explored through the activityguided approach. Here, we describe a gene-guided approach to discover and engineer a class of plant ribosomal peptides, the branched cyclic lyciumins. Initially isolated from the Chinese wolfberry Lycium barbarum, lyciumins are protease-inhibiting peptides featuring an N-terminal pyroglutamate and a macrocyclic bond between a tryptophan-indole nitrogen and a glycine α-carbon. We report the identification of a lyciumin precursor gene from L. barbarum, which encodes a BURP domain and repetitive lyciumin precursor peptide motifs. Genome mining enabled by this initial finding revealed rich lyciumin genotypes and chemotypes widespread in flowering plants. We establish a biosynthetic framework of lyciumins and demonstrate the feasibility of producing diverse natural and unnatural lyciumins in transgenic tobacco. With rapidly expanding plant genome resources, our approach will complement bioactivity-guided approaches to unlock and engineer hidden plant peptide chemistry for pharmaceutical and agrochemical applications. lyciumins | BURP domain | ribosomal peptides | natural products | plant metabolism P lants have been an important source of traditional medicines in many cultures for millennia. Underlying the historic use of medicinal plants are bioactive natural products produced in these organisms for signaling and defense (1). Most plant natural products with potential pharmacological applications were discovered based on their bioactivity in bioprospecting studies inspired by traditional herbal medicines (2). However, bioactivityguided discovery of new plant natural products faces a major bottleneck in rediscovery of known structures after purification via bioassay-guided fractionation (3). Subsequent drug development of a target plant natural product is also hindered by low isolation yields from the source plant and by structural complexity of the target compounds, where large-scale total synthesis of these compounds via organic chemistry is often infeasible (4).Over the last two decades, advances in genome sequencing, analytical chemistry, and synthetic biology allowed researchers to address these problems in microbial and fungal natural product chemistry (5). An increasing resource of microbial and fungal genomes enabled the development of powerful computational discovery pipelines for new natural product chemistry, using geneguided discovery approaches such as genome mining, in which a predicted genotype is connected to a chemotype by applying biosynthetic knowledge (5-7). Furthermore, mass spectrometry-based metabolomics accelerated discovery of new chemotypes from microbes and fungi in the context of growing genomic information (6, 8), while heterologous expression and metabolic engineering of biosynthetic gene clusters enabled source organism-independent production and diversification of natural products (9). More recently, analogous gene-guided approaches have been developed to chara...

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confidence: 99%

Gene-guided discovery and engineering of branched cyclic peptides in plants

Kersten

Weng

2018

Proc. Natl. Acad. Sci. U.S.A.

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“…This gave way to the concept of a single plant metabolite as a "magic bullet" to treat a disease. 7 The "one drug, one target, one disease" concept has been the prevailing motto in pharmaceutical research and therapeutics. However, the complex etiology and multifactorial nature of certain chronic diseases such as cancer, atherosclerosis and diabetes has shifted the course.…”

Section: The Intrinsic Polypharmacological Nature Of Herbal Medicinesmentioning

confidence: 99%

Herbal medicines on the spot: back to the green essentials

Dobrecky

Lucangioli

Wagner

2019

JAPLR

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Plants have always been an attractive source of new molecular entities, many of which hold potential for therapeutic purposes. From an analytical point of view, they pose a challenge since their compounds act in a synergistic way. Hence, powerful analytical techniques and data processing tools are put in place to unravel the green mystery. The aim of this mini review is to revisit key topics in the field of herbal medicines, such as main concepts of the trade, strategies to analyze complex mixtures, cutting-edge technologies and data processing tools to serve this purpose.Citation: Lucangioli SE, Wagner ML, Dobrecky CB. Herbal medicines on the spot: back to the green essentials.Citation: Lucangioli SE, Wagner ML, Dobrecky CB. Herbal medicines on the spot: back to the green essentials.Citation: Lucangioli SE, Wagner ML, Dobrecky CB. Herbal medicines on the spot: back to the green essentials.

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“…For centuries, traditional herbal medicine are used to treat a myriad of maladies，and simultaneously made great achievements (11) (12). Bioactive compounds from herbal medicine participate reduction of cholesterol synthesis, elevation of reverse cholesterol transport, and promotion of cholesterol excretion in the liver (13).…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota Mediates the Protective Effects of Andrographolide Inhibits Inflammation and Nonalcoholic Fatty Liver Disease(NAFLD) in High-Fat Diet induced ApoE(-/-) Mice

Shi

et al. 2020

Preprint

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Mechanisms relating the gut bacteria to Nonalcoholic Fatty Liver Disease (NAFLD) have been proposed containing the dysbiosis-induced dysregulation of hepatic lipid metabolism that allows for the translocation of microbial components and leads to hepatic inflammation and steatosis. Andrographolide (AG) regulates inflammation mediated by NF-κB pathway which also play a key role in reduction of inflammation and fibrosis in experimental nonalcoholic steatohepatitis (NASH), yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that ApoE knockout (Apoe -/-) mice fed a high-fat diet (HFD) supplemented with AG regulates levels of biochemical index and inflammatory cytokines associated with gut microbe. Moreover, HEPG2 cells induced by ox-LDL were used as validation in vitro. H&E staining and Oil-Red staining were respectively used for tissue and cells morphology. Gut microbiota were examined by 16S rRNA sequencing. Expression of NF-κB, C/EBPβ and PPAR-γ in liver and HEPG2 cells were detected by western blot and qRT-PCR. The results showed, among others, that AG alleviate hepatic steatosis and fat content in HEPG2 cells, while it induced decreased levels of Bacteroides, and increased levels of Faecalibaculum, Akkermansia. We further identified that inhibition of NF-κB/C/EBPβ/PPAR-γ pathway of hepatic steatosis model in vivo and vitro by AG also contributes to prevention of HFD-induced inflammation and dislipidemia. Importantly, as result of pearson correlation, Bacteroides may be the most relevant one fundamentally involved in the mechanism of AG attenuates NAFLD. Together, our findings uncover an interaction between AG and gut microbiota as a novel mechanism for the anti-NAFLD effect of AG acting through prevention of microbial dysbiosis, dislipidemia and inflammation.Importance HFD due to gut microbial dysbiosis is a major contributor to the pathogenesis of dislipidemia and inflammation, which primarily mediates the development of NAFLD. A treatment strategy to reduce both dislipidemia and inflammation appears to be an effective approach for addressing the issue of NAFLD. Andrographolide (AG) is the major effect component in traditional Chinese medicine Chuan-xin-lian (Andrographis). Little is known about the role of gut microbiota in the anti-NAFLD effect of AG. 16S rRNA gene sequencing revealed that AG significantly decreased Bacteroides and increased Faecalibaculum, Akkermansia. By using vivo and vitro experiment, we prove that gut microbiota plays a key role in AG-induced protective against high-fat-diet-induced dislipidemia and inflammation. Moreover, NF-κB/C/EBPβ/PPAR-γ pathway inhibition was partially involved in the beneficial effect of AG. Together, these data suggest that the gut microbiome is a critical factor for the anti-NAFLD effects of AG.

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Demystifying traditional herbal medicine with modern approach

Cited by 345 publications

References 60 publications

Gene-guided discovery and engineering of branched cyclic peptides in plants

Gene-guided discovery and engineering of branched cyclic peptides in plants

Herbal medicines on the spot: back to the green essentials

Gut Microbiota Mediates the Protective Effects of Andrographolide Inhibits Inflammation and Nonalcoholic Fatty Liver Disease(NAFLD) in High-Fat Diet induced ApoE(-/-) Mice

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