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1.
Plant J ; 119(1): 252-265, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38596892

ABSTRACT

Chicoric acid is the major active ingredient of the world-popular medicinal plant purple coneflower (Echinacea purpurea (L.) Menoch). It is recognized as the quality index of commercial hot-selling Echinacea products. While the biosynthetic pathway of chicoric acid in purple coneflower has been elucidated recently, its regulatory network remains elusive. Through co-expression and phylogenetic analysis, we found EpMYB2, a typical R2R3-type MYB transcription factor (TF) responsive to methyl jasmonate (MeJA) simulation, is a positive regulator of chicoric acid biosynthesis. In addition to directly regulating chicoric acid biosynthetic genes, EpMYB2 positively regulates genes of the upstream shikimate pathway. We also found that EpMYC2 could activate the expression of EpMYB2 by binding to its G-box site, and the EpMYC2-EpMYB2 module is involved in the MeJA-induced chicoric acid biosynthesis. Overall, we identified an MYB TF that positively regulates the biosynthesis of chicoric acid by activating both primary and specialized metabolic genes. EpMYB2 links the gap between the JA signaling pathway and chicoric acid biosynthesis. This work opens a new direction toward engineering purple coneflower with higher medicinal qualities.


Subject(s)
Caffeic Acids , Echinacea , Gene Expression Regulation, Plant , Plant Proteins , Succinates , Transcription Factors , Plant Proteins/genetics , Plant Proteins/metabolism , Succinates/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Caffeic Acids/metabolism , Echinacea/genetics , Echinacea/metabolism , Oxylipins/metabolism , Oxylipins/pharmacology , Cyclopentanes/metabolism , Cyclopentanes/pharmacology , Phylogeny , Acetates/pharmacology
2.
Phytother Res ; 38(6): 3190-3217, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38634408

ABSTRACT

Lutein is a naturally occurring carotenoid synthesized by plants and algae that has a beneficial effect on several biological processes and associated ailments. Its immediate application is in ophthalmology, where it significantly lowers the incidences of age-related macular degeneration (AMD). It also has anti-inflammatory action, treatment of diabetic retinopathy, and cataracts, and enhancement of visual contrast. To critically assess lutein biosynthesis, therapeutic applicability, and market research literature. We have discussed its theoretical frameworks, experimental evidence, limitations, as well as clinical trial results, and future research prospects. The literature for this review article was mined and compiled by collecting and analyzing articles from several databases, including ScienceDirect, Google Scholar, PubMed, Wiley Online Library, Patentscope, and ClinicalTrials.gov published until March 30, 2022. Patent publications were identified using the search terms like IC:(C07C67/56) AND EN_AB:(lutein) OR EN_TI:(lutein) OR EN_AB:(extraction) OR EN_TI:(process). According to the literature, lutein is an essential nutrient given that it cannot be synthesized in the human body and acts as an antioxidant, affecting AMD, diabetic retinopathy, Rheumatic diseases, inflammation, and cancer. Due to inadequate production and laborious extraction, lutein is expensive despite its high demand and applicability. Market research predicts a 6.3% compound annual growth rate for lutein by 2032. Optimizing lutein extraction for high yield and purity is necessary. Lutein has proven applicability in various ailments as well as cosmetics that can be developed as a candidate drug for various diseases discussed in the review.


Subject(s)
Lutein , Humans , Lutein/therapeutic use , Lutein/pharmacology , Macular Degeneration/drug therapy , Antioxidants/pharmacology , Antioxidants/therapeutic use , Diabetic Retinopathy/drug therapy , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use
3.
J Biol Chem ; 300(5): 107269, 2024 May.
Article in English | MEDLINE | ID: mdl-38588811

ABSTRACT

Coenzyme Q10 (CoQ10) is an important cofactor and antioxidant for numerous cellular processes, and its deficiency has been linked to human disorders including mitochondrial disease, heart failure, Parkinson's disease, and hypertension. Unfortunately, treatment with exogenous CoQ10 is often ineffective, likely due to its extreme hydrophobicity and high molecular weight. Here, we show that less hydrophobic CoQ species with shorter isoprenoid tails can serve as viable substitutes for CoQ10 in human cells. We demonstrate that CoQ4 can perform multiple functions of CoQ10 in CoQ-deficient cells at markedly lower treatment concentrations, motivating further investigation of CoQ4 as a supplement for CoQ10 deficiencies. In addition, we describe the synthesis and evaluation of an initial set of compounds designed to target CoQ4 selectively to mitochondria using triphenylphosphonium. Our results indicate that select versions of these compounds can successfully be delivered to mitochondria in a cell model and be cleaved to produce CoQ4, laying the groundwork for further development.


Subject(s)
Ataxia , Mitochondria , Mitochondrial Diseases , Muscle Weakness , Ubiquinone , Humans , Mitochondria/enzymology , Mitochondrial Diseases/enzymology , Mitochondrial Diseases/genetics , Muscle Weakness/enzymology , Muscle Weakness/genetics , Ubiquinone/analogs & derivatives , Ubiquinone/deficiency , Hep G2 Cells
4.
Int J Mol Sci ; 25(7)2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38612797

ABSTRACT

Carbon (C) and nitrogen (N) metabolisms participate in N source-regulated secondary metabolism in medicinal plants, but the specific mechanisms involved remain to be investigated. By using nitrate (NN), ammonium (AN), urea (UN), and glycine (GN), respectively, as sole N sources, we found that N sources remarkably affected the contents of diterpenoid lactone components along with C and N metabolisms reprograming in Andrographis paniculata, as compared to NN, the other three N sources raised the levels of 14-deoxyandrographolide, andrographolide, dehydroandrographolide (except UN), and neoandrographolide (except AN) with a prominent accumulation of farnesyl pyrophosphate (FPP). These N sources also raised the photosynthetic rate and the levels of fructose and/or sucrose but reduced the activities of phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoenolpyruvate carboxylase (PEPC) and pyruvate dehydrogenase (PDH). Conversely, phosphoenolpyruvate carboxykinase (PEPCK) and malate enzyme (ME) activities were upregulated. Simultaneously, citrate, cis-aconitate and isocitrate levels declined, and N assimilation was inhibited. These results indicated that AN, UN and GN reduced the metabolic flow of carbohydrates from glycolysis into the TCA cycle and downstream N assimilation. Furthermore, they enhanced arginine and GABA metabolism, which increased C replenishment of the TCA cycle, and increased ethylene and salicylic acid (SA) levels. Thus, we proposed that the N sources reprogrammed C and N metabolism, attenuating the competition of N assimilation for C, and promoting the synthesis and accumulation of andrographolide through plant hormone signaling. To obtain a higher production of andrographolide in A. paniculata, AN fertilizer is recommended in its N management.


Subject(s)
Andrographis paniculata , Diterpenes , Plant Extracts , Carbon , Seedlings
5.
Cureus ; 16(3): e56355, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38633965

ABSTRACT

Background Currently, nanotechnology is a rapidly advancing field of research. Because of their nanoscale dimensions, nanoparticles (NPs) find application in a wide range of industries, including engineering and medicine. The leaves of Suaeda monoica have anti-inflammatory qualities. The purpose of this study was to create SrO NPs isolated from the leaves of S. monoica aqueous extract and to evaluate their anti-inflammatory efficacy. The S. monoica saltmarsh, commonly known as South-Indian Seepweed, is a mangrove-associated plant and has been used as traditional medicine for decades with multifunctional biological activity. Objectives The aim of our study is to biosynthesize strontium oxide NPs from S. monoica saltmarsh and to see whether they have any anti-inflammatory properties. Materials and methods In the present study, the pharmacological significance was studied using crude extract and synthesized SrO NPs from S. monoica. The synthesized SrO NPs were characterized using UV spectrophotometry. The in vitro anti-inflammatory assay was analyzed using egg albumin denaturation. SrO NPs' peak observance was found at 630 nm, and a graph was plotted for the zone of inhibition vs concentration and compared with the standard.  Results It was observed that the color of the SrO NPs deepened during the synthesis process. Furthermore, at a wavelength of 630 nm, the UV spectrum analysis showed a noteworthy absorption value of 1.4. The activity of inflammatory enzymes is significantly impacted by the anti-inflammatory properties of SrO NPs in the protein denaturation inhibition test. Conclusions The application of SrO NPs in the synthesis process has the potential to enhance the anti-inflammatory activity of Suaeda monoica as evidenced by the observed increase in anti-inflammatory capacity and defense against infections and injury.

6.
Nanomaterials (Basel) ; 14(8)2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38668204

ABSTRACT

The biosynthesis of silver nanoparticles (AgNPs) using plant extracts has become a safe replacement for conventional chemical synthesis methods to fight plant pathogens. In this study, the antifungal activity of biosynthesized AgNPs was evaluated both in vitro and under greenhouse conditions against root rot fungi of common beans (Phaseolus vulgaris L.), including Macrophomina phaseolina, Pythium graminicola, Rhizoctonia solani, and Sclerotium rolfsii. Among the eleven biosynthesized AgNPs, those synthesized using Alhagi graecorum plant extract displayed the highest efficacy in suppressing those fungi. The findings showed that using AgNPs made with A. graecorum at a concentration of 100 µg/mL greatly slowed down the growth of mycelium for R. solani, P. graminicola, S. rolfsii, and M. phaseolina by 92.60%, 94.44%, 75.93%, and 79.63%, respectively. Additionally, the minimum inhibitory concentration (75 µg/mL) of AgNPs synthesized by A. graecorum was very effective against all of these fungi, lowering the pre-emergence damping-off, post-emergence damping-off, and disease percent and severity in vitro and greenhouse conditions. Additionally, the treatment with AgNPs led to increased root length, shoot length, fresh weight, dry weight, and vigor index of bean seedlings compared to the control group. The synthesis of nanoparticles using A. graecorum was confirmed using various physicochemical techniques, including UV spectroscopy, Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS) analysis. Collectively, the findings of this study highlight the potential of AgNPs as an effective and environmentally sustainable approach for controlling root rot fungi in beans.

7.
Curr Issues Mol Biol ; 46(4): 2884-2925, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38666911

ABSTRACT

At present, the occurrence of a large number of infectious and non-communicable diseases poses a serious threat to human health as well as to drug development for the treatment of these diseases. One of the most significant challenges is finding new drug candidates that are therapeutically effective and have few or no side effects. In this respect, the active compounds in medicinal plants, especially flavonoids, are potentially useful compounds with a wide range of pharmacological activities. They are naturally present in nature and valuable in the treatment of many infectious and non-communicable diseases. Flavonoids are divided into fourteen categories and are mainly derived from plant extraction, chemical synthesis and structural modification, and biosynthesis. The structural modification of flavonoids is an important way to discover new drugs, but biosynthesis is currently considered the most promising research direction with the potential to revolutionize the new production pipeline in the synthesis of flavonoids. However, relevant problems such as metabolic pathway analyses and cell synthesis protocols for flavonoids need to be addressed on an urgent basis. In the present review, new research techniques for assessing the biological activities of flavonoids and the mechanisms of their biological activities are elucidated and their modes of interaction with other drugs are described. Moreover, novel drug delivery systems, such as nanoparticles, bioparticles, colloidals, etc., are gradually becoming new means of addressing the issues of poor hydrophilicity, lipophilicity, poor chemical stability, and low bioavailability of flavonoids. The present review summarizes the latest research progress on flavonoids, existing problems with their therapeutic efficacy, and how these issues can be solved with the research on flavonoids.

9.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1144-1153, 2024 Mar.
Article in Chinese | MEDLINE | ID: mdl-38621961

ABSTRACT

Agaricus blazei is a rare medicinal and edible fungus with a crispy taste and delicious flavor. Both fruiting body and mycelium are rich in polysaccharides, sterols, terpenoids, peptides, lipids, polyphenols, and other active ingredients, which have strong pharmacological activities such as anti-tumor, lipid-lowering, glucose-lowering, immunomodulation, optimization of intestinal flora, and anti-oxidation. Therefore, it is a kind of fungal resource with a great prospect of edible and medicinal development. Among the reported chemical components of A. blazei, blazeispirol is a series of sterol compounds unique to A. blazei, which has a spiral structure and is different from classical steroids. It is an important active ingredient found in the mycelium of A. blazei and has significant hepatoprotective activity. It can be used as a phylogenetic and chemotaxonomic marker of A. blazei strains and is considered an excellent lead compound for drug development. According to the skeleton structure characteristics, the 17 discovered blazeispirol compounds can be divided into two types: blazeispirane and problazeispirane. In order to further explore the resource of blazeispirol compounds of A. blazei, the discovery, isolation, structure, biological activity, and biosynthetic pathways of blazeispirol compounds of A. blazei were systematically reviewed. Besides, the metabolic regulation strategies related to the fermentation synthesis of blazeispirol A by A. blazei were discussed. This review could provide a reference for the efficient synthesis and development of blazeispirol compounds, the research and development of related drugs and functional foods, and the quality improvement of A. blazei and other medicinal and edible fungi resources and derivatives.


Subject(s)
Agaricus , Neoplasms , Phylogeny , Polysaccharides , Steroids , Agaricus/chemistry , Agaricus/metabolism
10.
Int J Mol Sci ; 25(7)2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38612877

ABSTRACT

Hedera helix is a traditional medicinal plant. Its primary active ingredients are oleanane-type saponins, which have extensive pharmacological effects such as gastric mucosal protection, autophagy regulation actions, and antiviral properties. However, the glycosylation-modifying enzymes responsible for catalyzing oleanane-type saponin biosynthesis remain unidentified. Through transcriptome, cluster analysis, and PSPG structural domain, this study preliminarily screened four candidate UDP-glycosyltransferases (UGTs), including Unigene26859, Unigene31717, CL11391.Contig2, and CL144.Contig9. In in vitro enzymatic reactions, it has been observed that Unigene26859 (HhUGT74AG11) has the ability to facilitate the conversion of oleanolic acid, resulting in the production of oleanolic acid 28-O-glucopyranosyl ester. Moreover, HhUGT74AG11 exhibits extensive substrate hybridity and specific stereoselectivity and can transfer glycosyl donors to the C-28 site of various oleanane-type triterpenoids (hederagenin and calenduloside E) and the C-7 site of flavonoids (tectorigenin). Cluster analysis found that HhUGT74AG11 is clustered together with functionally identified genes AeUGT74AG6, CaUGT74AG2, and PgUGT74AE2, further verifying the possible reason for HhUGT74AG11 catalyzing substrate generalization. In this study, a novel glycosyltransferase, HhUGT74AG11, was characterized that plays a role in oleanane-type saponins biosynthesis in H. helix, providing a theoretical basis for the production of rare and valuable triterpenoid saponins.


Subject(s)
Hedera , Oleanolic Acid/analogs & derivatives , Saponins , Glycosyltransferases/genetics
11.
Zhongguo Zhong Yao Za Zhi ; 49(4): 932-941, 2024 Feb.
Article in Chinese | MEDLINE | ID: mdl-38621900

ABSTRACT

This study explored the biosynthesis of bufadienolides(BDs) in Bufo bufo gargarizans to solve the dilemma of the decreasing resources of B. bufo gargarizans and provide a theoretical basis for the sustainable utilization of the resources. Ultra-high performance liquid chromatography-Orbitrap-mass spectrometry(UHPLC-Orbitrap-MS) was employed to detect the synthesis sites of BDs in B. bufo gargarizans, and the results were verified by desorption electrospray ionization-mass spectrometry imaging(DESI-MSI) and homogenate incubation experiments. BDs in B. bufo gargarizans had the highest content in the liver and the highest concentration in the gallbladder, in addition to the parotid gland and skin, which suggested that the liver could synthesize BDs. The results of DESI-MSI also showed that BDs were mainly enriched in the liver rather than the immature parotid gland. The incubation experiment of liver homogenates demonstrated the liver of B. bufo gargarizans had the ability to synthesize BDs. This study showed that the liver was a major organ for the synthesis of BDs in B. bufo gargarizans during metamorphosis, development, and growth, which provided strong theoretical support for the biosynthesis of BDs and the sustainable utilization of B. bufo gargarizans resources.


Subject(s)
Bufanolides , Animals , Bufo bufo , Tissue Distribution , Bufonidae , Spectrometry, Mass, Electrospray Ionization
12.
J Pharm Pharmacol ; 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38579142

ABSTRACT

OBJECTIVES: To get a better understanding of the scientific values of flavone scutellarein (SCT), and to encourage its applications in human health, the current review systematically summarizes the natural observation, biosynthesis, synthesis, pharmacology, pharmacokinetics, and recent synthetic advances. KEY FINDINGS: Scientific sources to search for references included Google Scholar, Scopus, Web of Science, PubMed, Sci-Finder, and journal websites. The references have been collected from the 1970s to the present. "Scutellarein" is the most meaningful keyword to search for publications, in which it was used alone or in combination with other keywords. SUMMARYS: SCT as a hydrophobic flavonoid can be found in various medicinal plants of the families Lamiaceae, Compositae, and Verbenaceae. Flavone SCT has drawn much interest due to its wide pharmacological effects, such as anticancer, anti-inflammation, antioxidant, antiobesity, and vasorelaxant. The SCT treatments also possessed a lot of positive results in the neuron, liver, heart, lung, kidney, bone, and skin protective experiments, and human sperm function enhancement. Its underlying mechanism of action may relate to the apoptotic program and cytokine inhibition by regulating a panel of the signaling pathway, e.g., NF-κB (nuclear factor kappa B)/MAPK (mitogen-activated protein kinase), IκBa (nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitors alpha)/NF-κB, TRAF2 (tumor necrosis factor receptor-associated factor 2)/NF-κB, and PTEN (phosphatase and tension homologue deleted on chromosome 10)/Akt (protein kinase B)/NF-κB. In addition, the metabolic actions and synthetic derivative promotions of SCT were mostly based on the substitution of hydroxyl groups. Collectively, the studies that aim to highlight the role of scutellarein in preclinical and clinical treatments are urgently needed. More and more experiments to improve its bioavailability are expected.

13.
Genes (Basel) ; 15(3)2024 02 21.
Article in English | MEDLINE | ID: mdl-38540329

ABSTRACT

Kadsura coccinea is a medicinal plant from the Schisandraceae family that is native to China and has great pharmacological potential due to its lignans. However, there are significant knowledge gaps regarding the genetic and molecular mechanisms of lignans. We used transcriptome sequencing technology to analyze root, stem, and leaf samples, focusing on the identification and phylogenetic analysis of Cytochrome P450 (CYP) genes. High-quality data containing 158,385 transcripts and 68,978 unigenes were obtained. In addition, 36,293 unigenes in at least one database, and 23,335 across five databases (Nr, KEGG, KOG, TrEMBL, and SwissProt) were successfully annotated. The KEGG pathway classification and annotation of these unigenes identified 10,825 categorized into major metabolic pathways, notably phenylpropanoid biosynthesis, which is essential for lignan synthesis. A key focus was the identification and phylogenetic analysis of 233 Cytochrome P450 (CYP) genes, revealing their distribution across 38 families in eight clans, with roots showing specific CYP gene expression patterns indicative of their role in lignan biosynthesis. Sequence alignment identified 22 homologous single genes of these CYPs, with 6 homologous genes of CYP719As and 1 of CYP81Qs highly expressed in roots. Our study significantly advances the understanding of the biosynthesis of dibenzocyclooctadiene lignans, offering valuable insights for future pharmacological research and development.


Subject(s)
Kadsura , Lignans , Humans , Transcriptome/genetics , Phylogeny , Gene Expression Profiling , Cytochrome P-450 Enzyme System/genetics , Lignans/pharmacology
14.
Fitoterapia ; 175: 105914, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38508500

ABSTRACT

The OSMAC (one strain many compounds) concept is a cultivation-based approach to increase the diversity of secondary metabolites in microorganisms. In this study, we applied the OSMAC-approach to the endophytic fungus Trichocladium sp. by supplementation of the cultivation medium with 2.5% phenylalanine. This experiment yielded five new compounds, trichocladiol (1), trichocladic acid (2), colletodiolic acid (3), colletolactone (4) and colletolic acid (5), together with five previously described ones (6-10). The structures were elucidated via comprehensive spectroscopic measurements, and the absolute configurations of compound 1 was elucidated by using TDDFT-ECD calculations. For formation of compounds 3-5, a pathway based on colletodiol biosynthesis is proposed. Compound 6 exhibited strong antibacterial activity against methicillin-resistant Staphylococcus aureus with a minimal inhibitory concentration (MIC) of 0.78 µM as well as a strong cytotoxic effect against the human monocytic cell line THP1 with an IC50 of 0.7 µM. Compound 8 showed moderate antibacterial activity against Mycobacterium tuberculosis with a MIC of 25 µM and a weak cytotoxic effect against THP1 cells with an IC50 of 42 µM.


Subject(s)
Anti-Bacterial Agents , Endophytes , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Mycobacterium tuberculosis , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/chemistry , Molecular Structure , Methicillin-Resistant Staphylococcus aureus/drug effects , Mycobacterium tuberculosis/drug effects , Endophytes/chemistry , Hypocreales/chemistry , THP-1 Cells , China
15.
J Genet Eng Biotechnol ; 22(1): 100344, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38494263

ABSTRACT

BACKGROUND: Gymnema sylvestre R.Br. is famous medicinal plant among diabetics for its gymnemic acid content. It also contains flavonoids, which are an essential component in various other products. Though some molecular information on the biosynthesis of gymnemic acid, polyoxypregnane, micro RNAs and photosynthetic efficiency is available, there is no gene level information available on the biosynthesis of flavonoids in this plant. RNA was extracted from winter-collected Gymnema sylvestre leaves and cDNA libraries were prepared and used for next generation sequencing. De novo transcriptome assembly were prepared and Coding DNA Sequences (CDS) of 13 major genes involved in flavonoids biosynthesis were identified from transcriptome data. Phenylalanine ammonia lyase gene containing full-length CDS was employed for in silico protein modelling and subsequent quality assessment. These models were then compared against publicly available databases. To confirm the identification of these genes, a similarity search was conducted using the NCBI BLAST tool. RESULTS: Therefore, in the present study, an effort has been made to provide molecular insights into flavonoid biosynthesis pathway by examining the expressed transcripts in G.sylvestre. Gene sequences of total thirteen major genes viz., phenylalanine ammonia lyase, 4-coumarate CoA ligase, cinnamic acid 4-hydroxylase, shikimate O-hydroxycinnamoyl transferase, coumaroyl quinate (coumaroyl shikimate) 3'-monooxygenase, caffeoyl-CoA O-methyltransferase, chalcone synthase, chalcone isomerase, naringenin 3-dioxygenase, flavanol synthase, flavonoid 3'-monooxygenase, Flavanone 7-O-glucoside 2″-O-beta-L-rhyamnosyltransferase and leucoanthocyanidin dioxygenase were identified and a putative pathway of flavonoids biosynthesis has been illustrated based on transcriptome data. CONCLUSIONS: This transcriptome study has contributed gene-level insights into the biosynthesis of flavonoids in plants as a whole and represents the first report within a non-model plant, Gymnema sylvestre perticullarly.

16.
Comput Struct Biotechnol J ; 23: 1106-1116, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38495554

ABSTRACT

Flavonoid glycosides are widespread in plants, and are of great interest owing to their diverse biological activities and effectiveness in preventing chronic diseases. Periploca forrestii, a renowned medicinal plant of the Apocynaceae family, contains diverse flavonoid glycosides and is clinically used to treat rheumatoid arthritis and traumatic injuries. However, the mechanisms underlying the biosynthesis of these flavonoid glycosides have not yet been elucidated. In this study, we used widely targeted metabolomics and full-length transcriptome sequencing to identify flavonoid diversity and biosynthetic genes in P. forrestii. A total of 120 flavonoid glycosides, including 21 C-, 96 O-, and 3 C/O-glycosides, were identified and annotated. Based on 24,123 full-length coding sequences, 99 uridine diphosphate sugar-utilizing glycosyltransferases (UGTs) were identified and classified into 14 groups. Biochemical assays revealed that four UGTs exhibited O-glycosyltransferase activity toward apigenin and luteolin. Among them, PfUGT74B4 and PfUGT92A8 were highly promiscuous and exhibited multisite O-glycosylation or consecutive glycosylation activities toward various flavonoid aglycones. These four glycosyltransferases may significantly contribute to the diversity of flavonoid glycosides in P. forrestii. Our findings provide a valuable genetic resource for further studies on P. forrestii and insights into the metabolic engineering of bioactive flavonoid glycosides.

17.
Int J Biol Macromol ; 266(Pt 1): 131012, 2024 May.
Article in English | MEDLINE | ID: mdl-38522709

ABSTRACT

Medicinal tropane alkaloids (TAs), including hyoscyamine, anisodamine and scopolamine, are essential anticholinergic drugs specifically produced in several solanaceous plants. Atropa belladonna is one of the most important medicinal plants that produces TAs. Therefore, it is necessary to cultivate new A. belladonna germplasm with the high content of TAs. Here, we found that the levels of TAs were elevated under low nitrogen (LN) condition, and identified a LN-responsive bHLH transcription factor (TF) of A. belladonna (named LNIR) regulating the biosynthesis of TAs. The expression level of LNIR was highest in secondary roots where TAs are synthesized specifically, and was significantly induced by LN. Further research revealed that LNIR directly activated the transcription of hyoscyamine 6ß-hydroxylase gene (H6H) by binding to its promoter, which converts hyoscyamine into anisodamine and subsequently epoxidizes anisodamine to form scopolamine. Overexpression of LNIR upregulated the expression levels of TA biosynthesis genes and consequently led to the increased production of TAs. In summary, we functionally identified a LN-responsive bHLH gene that facilitated the development of A. belladonna with high-yield TAs under the decreased usage of nitrogen fertilizer.


Subject(s)
Atropa belladonna , Basic Helix-Loop-Helix Transcription Factors , Gene Expression Regulation, Plant , Mixed Function Oxygenases , Nitrogen , Tropanes , Nitrogen/metabolism , Gene Expression Regulation, Plant/drug effects , Atropa belladonna/metabolism , Atropa belladonna/genetics , Tropanes/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Medicinal/metabolism , Plants, Medicinal/genetics , Hyoscyamine/metabolism , Hyoscyamine/genetics , Scopolamine/metabolism , Promoter Regions, Genetic
18.
Front Plant Sci ; 15: 1368869, 2024.
Article in English | MEDLINE | ID: mdl-38545395

ABSTRACT

Background: Thymus mandschuricus is an aromatic and medicinal plant with notable antibacterial and antioxidant properties. However, traditional breeding methods rely on phenotypic selection due to a lack of molecular resources. A high-quality reference genome is crucial for marker-assisted breeding, genome editing, and molecular genetics. Results: We utilized PacBio and Hi-C technologies to generate a high-quality chromosome-level reference genome for T. mandschuricus, with a size of 587.05 Mb and an N50 contig size of 8.41 Mb. The assembled genome contained 29,343 predicted protein-coding genes, and evidence of two distinct whole-genome duplications in T. mandschuricus was discovered. Comparative genomic analysis revealed rapid evolution of genes involved in phenylpropanoid biosynthesis and the CYP450 gene family in T. mandschuricus. Additionally, we reconstructed the gene families of terpenoid biosynthesis structural genes, such as TPS, BAHD, and CYP, and identified regulatory networks controlling the expression of aroma-synthesis genes by integrating transcriptome data from various organs and developmental stages. We discovered that hormones and transcription factors may collaborate in controlling aroma-synthesis gene expression. Conclusion: This study provides the first high-quality genome sequence and gene annotation for T. mandschuricus, an indigenous thyme species unique to China. The genome assembly and the comprehension of the genetic basis of fragrance synthesis acquired from this research could potentially serve as targets for future breeding programs and functional studies.

19.
Acta Pharm Sin B ; 14(3): 1111-1131, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38486983

ABSTRACT

Conventional photodynamic therapy (PDT) approaches face challenges including limited light penetration, low uptake of photosensitizers by tumors, and lack of oxygen in tumor microenvironments. One promising solution is to internally generate light, photosensitizers, and oxygen. This can be accomplished through endogenous production, such as using bioluminescence as an endogenous light source, synthesizing genetically encodable photosensitizers in situ, and modifying cells genetically to express catalase enzymes. Furthermore, these strategies have been reinforced by the recent rapid advancements in synthetic biology. In this review, we summarize and discuss the approaches to overcome PDT obstacles by means of endogenous production of excitation light, photosensitizers, and oxygen. We envision that as synthetic biology advances, genetically engineered cells could act as precise and targeted "living factories" to produce PDT components, leading to enhanced performance of PDT.

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