Natural product-based antiviral candidates have received significant attention. However, there is a lack of sufficient research in the field of antivirals to effectively combat patterns of drug resistance. Baicalein and its glucuronide derivative baicalin are two main components extracted from Scutellaria baicalensis Georgi. They have proven to be effective against a broad range of viruses by directly killing virus particles, protecting infected cells, and targeting viral antigens on their surface, among other mechanisms. As natural products, they both possess the advantage of lower toxicity, enhanced therapeutic efficacy, and even antagonistic effects against drug-resistant viral strains. Baicalein and baicalin exhibit promising potential as potent pharmacophore scaffolds, demonstrating their antiviral properties. However, to date, no review on the antiviral effects of baicalein and baicalin has been published. This review summarizes the recent research progress on antiviral effects of baicalein and baicalin against various types of viruses both in vitro and in vivo with a focus on the dosages and underlying mechanisms. The aim is to provide a basis for the rational development and utilization of baicalein and baicalin, as well as to promote antiviral drug research. Please cite this article as: Liu XY, Xie W, Zhou HY, Zhang HQ, Jin YS. A comprehensive overview on antiviral effects of baicalein and its glucuronide derivative baicalin. J Integr Med. 2024; 22(6): 621-636.
Flavanones/chemistry* ; Flavonoids/chemistry* ; Antiviral Agents/chemistry* ; Humans ; Scutellaria baicalensis/chemistry* ; Animals ; Glucuronides/chemistry*

Dead heart is an important trait of pith-decayed Scutellariae Radix. The purpose of this study was to clarify the scientific connotation of the dead heart using multi-omics. Metabolomics and transcriptomics combined with multivariate statistical analysis such as principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were used to systematically compare the differences in chemical composition and gene expression among phloem, outer xylem and near-dead xylem of pith-decayed Scutella-riae Radix. The results revealed significant differences in the contents of flavonoid glycosides and aglycones among the three parts. Compared with phloem and outer xylem, near-dead xylem had markedly lowered content of flavonoid glycosides(including baicalin, norwogonin-7-O-β-D-glucuronide, oroxylin A-7-O-β-D-glucuronide, and wogonoside) while markedly increased content of aglycones(including 3,5,7,2',6'-pentahydroxy dihydroflavone, baicalin, wogonin, and oroxylin A). The differentially expressed genes were mainly concentrated in KEGG pathways such as phenylpropanoid metabolism, flavonoid biosynthesis, ABC transporter, and plant MAPK signal transduction pathway. This study systematically elucidated the material basis of the dead heart of pith-decayed Scutellariae Radix with multiple growing years. Specifically, the content of flavonoid aglycones was significantly increased in the near-dead xylem, and the gene expression of metabolic pathways such as flavonoid glycoside hydrolysis, interxylary cork development and programmed apoptosis was significantly up-regulated. This study provided a theoretical basis for guiding the high-quality production of pith-decayed Scutellariae Radix.
Drugs, Chinese Herbal/chemistry* ; Scutellaria baicalensis/chemistry* ; Glucuronides ; Multiomics ; Flavonoids/chemistry*

To define the composition of relevant substances in Breviscapine for Injection, in order to improve the quality control of impurity, and ensure the clinical safety. The analysis and structural identification of relevant substances in different specifications and batches of Breviscapine for Injection powders were carried out by HPLC and UPLC-QTOF-MS. Three primary relevant substances, namely 5,6,7,3',4'-pentahydroxyflavone-7-O-glucuronide(3), 3,5,6,7,4'-pentahydroxyflavone-3-O-glucuronide(4) and scutellarein(10), as well as three minor impurities, namely 6-hydroxyapigenin-6-O-glucosyl-7-O-glucuronide(1), methoxylscutellarin(6) and apigenin-7-O-glucuronide(7) were structurally identified by matching retention time, UV spectra, and mass spectra with authentic compounds and MS fragmentation rules. The main relevant substances(3) and(4) were separated and purified by semi-preparative HPLC, and their structures were further confirmed by NMR data. The study defined relevant substances of Breviscapine for Injection, and provided reference for improving the quality control level of single impurity in breviscapine preparation.
Apigenin/analysis* ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/standards* ; Flavonoids/chemistry* ; Glucuronides/analysis* ; Injections ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Quality Control

Chlorogenic acid (5-CQA) is one of the major components in some Chinese herbal injections. However, the metabolism of 5-CQA in rats after intravenous injection has not been determined. An ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) method was applied to identify the metabolites in bile, urine, feces and plasma after a single intravenous administration of 10 mg x kg(-1) 5-CQA to rats. Using MSE and mass defect filter techniques, a total of 35 metabolites were detected in bile, urine, feces and plasma. The predominant metabolites in bile were glutathione conjugates of O-methyl-5-CQA, accounting for approximately 80% of the metabolites excreted in bile. The major components in urine were parent drug, O-methyl-5-CQA, hydrolyzed metabolites and glucuronide conjugates. The major components in feces were O-methyl-5-CQA and its cysteine conjugates. The major component in plasma was the parent drug. The urinary and fecal excretion pathways were equally important to 5-CQA in rats. These results demonstrate that 5-CQA undergoes extensively metabolism in rats and are highly reactive to nucleophiles such as GSH. This finding indicates that attention should be paid on the injections containing 5-CQA, which may covalently bind to proteins, leading to allergenic drug reactions.
Animals ; Bile ; metabolism ; Biotransformation ; Chlorogenic Acid ; administration & dosage ; blood ; pharmacokinetics ; urine ; Chromatography, High Pressure Liquid ; methods ; Cysteine ; metabolism ; Feces ; chemistry ; Glucuronides ; metabolism ; Glutathione ; metabolism ; Injections, Intravenous ; Male ; Protein Binding ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods

OBJECTIVETo study the chemical constituents of Exochorda racemosa.

METHODCompounds were isolated and purified by silica gel, Sephadex LH-20, MCI gel and RP-18 column chromatography, and their structures were determined by spectroscopic analysis.

RESULTTwenty compounds were isolated and identified as N-p-coumaroyl-N'-caffeoylputrescine (1), sutherlandin trans-p-coumarate (2), apigenin 7-O-methylglucuronide (3), astragalin (4), nicotiflorin (5), kaempferol 3-neohesperidoside (6), rutin (7), apigenin (8), luteolin (9), linalool-1-oic acid (10), betulalbuside A (11), ursolic acid (12) , corosolic acid (13), gynuramide II (14), beta-sitosterol (15), daucosterol (16), uridine (17), adenosine (18), syringin (19), and trans4-hydroxycinnamic acid (20), respectively.

CONCLUSIONAll compounds were obtained from this plant for the first time, moreover, 1 was reported as a new natural product, and 2 is a naturally rare cyanogenic glycoside.

Apigenin ; chemistry ; Flavonoids ; chemistry ; Glucosides ; chemistry ; Glucuronides ; chemistry ; Kaempferols ; chemistry ; Luteolin ; chemistry ; Magnetic Resonance Spectroscopy ; Phenols ; chemistry ; Phenylpropionates ; chemistry ; Rosaceae ; chemistry ; Sitosterols ; chemistry ; Triterpenes ; chemistry

To analyze and identify the constituents in rat plasma after oral administration of the active fraction of Corydalis yanhusuo, a LC-MS/MS method was established. The constituents absorbed into blood, their original crude drugs and their metabolites were identified either by comparing the retention time and mass spectrometry data with that of reference compounds or by mass spectrometry analysis and retrieving the reference literatures. Nine species are the original form in Corydalis yanhusuo, moreover, some metabolites in blood identified as glucuronide were found. The constituents absorbed into blood and the possible metabolites which demonstrate to originate from the active fraction of Corydalis yanhusuo are responsible for the observed efficacy. Its serum pharmacochemistry should be subjected to complete investigation so as to illuminate the pharmacology and active mechanism of the active fraction of Corydalis yanhusuo.
Administration, Oral ; Alkaloids ; administration & dosage ; blood ; isolation & purification ; metabolism ; Animals ; Chromatography, High Pressure Liquid ; Corydalis ; chemistry ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; metabolism ; Glucuronides ; blood ; Male ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

OBJECTIVETo in vestigate the chemical constituents of Sarcandra glabra and obtain a more comprehensive understanding on its effective components.

METHODThe constituents were isolated by various column chromatographic method and their structures were elucidated by physico-chemical properties and spectroscopic analysis.

RESULTFive flavonoid glycosides were isolated and identified as kaempferol-3-O-beta-D-glucuronide (1), quercetin-3-O-alpha-D-glucuronide (2), quercetin-3-O-beta-D-glucuronopyranoside methyl ester (3), 5, 7, 4'-trihydroxy-8-C-beta-D-glucopyranosyl flavanone (4), neoastilbin (5), 5-O-caffeoylquinic acid methyl ester (6), 3, 4-dihydroxybenzoic acid (7), isofraxidin (8).

CONCLUSIONCompounds 1-6 were isolated from the genus Sarcandra for the first time. The glucuroide compounds compounds 1-3, were first isolated from the genus Sarcandra.

Caffeic Acids ; chemistry ; Coumarins ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Flavonoids ; chemistry ; Glucuronides ; chemistry ; Glycosides ; chemistry ; Magnetic Resonance Spectroscopy ; Magnoliopsida ; chemistry ; Spectrometry, Mass, Electrospray Ionization

AIMTo establish the fundamentals for the design of scutellarin prodrug and formulation with feasible physicochemical and biopharmaceutical properties by esterifying scutellarin, an active component with poor absorption extracted from Erigeron breviscapus of Chinese medicine.

METHODSWith the method of salifying followed by esterifying, ethyl and benzyl ester of scutellarin were synthesized. Glycolamide ester of scutellarin was also synthesized with an improved method. Their structures were confirmed by MS and 1H NMR. The solubility and partition coefficient of the prodrugs were determined and their degradations were investigated in various buffers and in human plasma. The emulsion and cyclodextrin complex of glycolamide ester were prepared and the protection of the ester from degradation was compared in the intestinal tract contents. Furthermore, the degradation of glycolamide ester in the homogenates of various intestinal segments was studied. Results Three prodrugs were synthesized successfully and their structures were confirmed. Glycolamide ester of scutellarin showed better stability in the aqueous solution (t(1/2) approximately =16 d, pH 4.2) and the shortest half-life in the human serum (t(1/2) approximately =7 min). Compared with scutellarin, the solubility of glycolamide ester was increased about ten times in pH 4.0 buffer, and about thirty five times in water. Partition coefficient of the glycolamide ester increased significantly from -2.56 to 1.48. However, the ester degradation in the homogenates of intestinal mucus would be an obstacle for its absorption. The degradation rates were in the order duodenum > ileum > or = jejunum > colon. The emulsion showed a better protection of glycolamide ester from the degradation than cyclodextrin complex.

CONCLUSIONGlycolamide ester of scutellarin shows better physicochemical properties than ethyl and benzyl eater of scutellarin, but its stability in intestinal tract needs to be improved. The emulsion or / and colon-targeted delivery may be selected as one of strategies to decrease the presystemic degradation.

Animals ; Apigenin ; chemistry ; isolation & purification ; pharmacokinetics ; Emulsions ; Erigeron ; chemistry ; Esters ; Flavones ; chemical synthesis ; chemistry ; pharmacokinetics ; Glucuronates ; chemistry ; isolation & purification ; pharmacokinetics ; Glucuronides ; chemical synthesis ; chemistry ; pharmacokinetics ; Humans ; Intestinal Mucosa ; metabolism ; Intestines ; metabolism ; Male ; Plants, Medicinal ; chemistry ; Prodrugs ; chemical synthesis ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley