This paper investigated the inhibitory effect of carbonized Scutellariae Radix(Cb-SR) on pyroptosis in endometrial epithelial cells of mice with endometritis and its correlation with the IKBKE/NLRP3 signaling axis. Mice model of endometritis was established by using an intrauterine injection of 10 μL polysaccharides(LPS, 5 mg·mL~(-1)), and the mice were randomly divided into model group(LPS), low-dose group of Cb-SR(L-Cb-SR, 0.55 g·kg~(-1)), medium-dose group of Cb-SR(M-Cb-SR, 1.10 g·kg~(-1)), high-dose group of Cb-SR(H-Cb-SR, 2.20 g·kg~(-1)), crude Scutellariae Radix group(Cr-SR, 1.63 g·kg~(-1)), and Fuke Qianjin Capsule group(FQC, 0.30 g·kg~(-1)), with 10 mice in each group. Ten healthy female mice were selected and injected with PBS of equal volume into the bilateral uterus, and they were set as the sham group. The mice in the drug treatment groups were given the corresponding doses of Cb-SR, Cr-SR, FQC, or physiological saline of equal volume by gavage twice a day for seven days. Thirty minutes after the last administration, each mouse was euthanized by cervical dislocation. Hematoxylin-eosin(HE) staining and transmission electron microscopy were applied to observe the histopathological morphology of the uterine tissue. Immunohistochemistry was used to detect the expression of CD38 and CD138. Myeloperoxidase(MPO) values in neutrophils were measured by the kit; Enzyme-linked immunosorbent assay(ELISA) was used to measure the secretion of interleukin-18(IL-18), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α). Immunofluorescence and Western blot were used to analyze the expression of the proteins related to the IKBKE/NLRP3 signaling axis. Mouse endometrial epithelial cells(MEECs) were separated and purified from the uterine tissue of pregnant female mice through in vitro experiments and injured by LPS for 24 h, and then they were cultured with Cb-SR-containing serum. The anti-endometritis effect of Cb-SR was investigated by CCK-8 assay, scanning electron microscopy, and Western blot. The results showed that Cb-SR significantly reduced MPO values, attenuated uterine tissue damage, inhibited the expression of CD38 and CD138, decreased the levels of IL-1β, IL-18, and TNF-α, and inhibited the expression of proteins associated with IKBKE/NLRP3 signaling axis in mice with endometritis. In addition, Cb-SR-containing serum reduced swelling of MEECs organelles induced by LPS, decreased the expression of inflammatory factors, and suppressed the expression of IKBKE/NLRP3 signaling axis-related proteins. These results suggest that Cb-SR can inhibit endometrial epithelial cell pyroptosis in endometritis by suppressing the IKBKE/NLRP3 signaling axis.
Animals ; Female ; Mice ; Pyroptosis/drug effects* ; Signal Transduction/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Drugs, Chinese Herbal/chemistry* ; Endometritis/chemically induced* ; Lipopolysaccharides/adverse effects* ; Scutellaria baicalensis/chemistry* ; Humans ; Epithelial Cells/drug effects*

This study aims to investigate the therapeutic effects of the Coptidis Rhizoma-Scutellariae Radix on cytokine storm secondary lung injury(CSSLI) induced by CpG1826 in mice, and to elucidate the potential molecular mechanisms by which its major active components, i.e., coptisine and wogonin, alleviate CSSLI by inhibiting the mitochondrial permeability transition pore(mPTP)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3) inflammasome pyroptosis pathway. In vivo, a mouse model of CSSLI was established by CpG1826 induction. Pulmonary edema was assessed by lung wet-to-dry weight ratio(W/D), lung injury was evaluated by hematoxylin-eosin(HE) staining, and ultrastructural changes in lung tissue were observed by transmission electron microscopy(TEM). The levels of interleukin(IL)-1β, high mobility group box 1 protein(HMGB1), IL-18, and IL-1α in bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay(ELISA). The results showed that the decoction of the Coptidis Rhizoma-Scutellariae Radix significantly reduced pulmonary edema, alleviated lung injury, and decreased the concentrations of related cytokines in BALF more effectively than either single herb alone, thereby improving CSSLI. In vitro, a CpG1826-induced CSSLI model was established in mouse alveolar macrophage MH-S cells. Calcein-AM quenching was used to screen for the most effective monomer components from the herb pair in inhibiting mPTP opening. Coptisine(5, 10, 20 μmol·L~(-1)) and wogonin(10, 20, 40 μmol·L~(-1)) markedly inhibited mPTP opening, with optimal effects and a clear dose-dependent pattern. These components suppressed mPTP opening, thereby reducing the release of mitochondrial DNA(mtDNA) and the accumulation of reactive oxygen species(ROS), effectively reversing the CpG1826-induced decrease in mitochondrial membrane potential(MMP). Further studies revealed that both coptisine and wogonin inhibited pyroptosis and downregulated the expression of key proteins in the NLRP3/Caspase-1/gasdermin D(GSDMD) pathway. In conclusion, the Coptidis Rhizoma-Scutellariae Radix improves CpG1826-induced CSSLI in mice, and this effect is associated with the inhibition of the mPTP/NLRP3 pyroptosis pathway, providing scientific evidence for its clinical application and further development.
Animals ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Pyroptosis/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Male ; Lung Injury/immunology* ; Cytokines/immunology* ; Scutellaria baicalensis/chemistry* ; Oligodeoxyribonucleotides/adverse effects* ; Mice, Inbred C57BL ; Coptis chinensis

Oroxylin A (OA), a natural compound extracted from Scutellaria baicalensis, demonstrates preventive potential against ultraviolet B (UVB)-induced non-melanoma skin cancer (NMSC), the most prevalent cancer worldwide with increasing incidence. Utilizing SKH-1 hairless mice exposed to UVB, this study showed that OA delayed NMSC onset and alleviated acute skin damage. Mechanistic investigations revealed its dual action: inhibiting inflammation and enhancing nucleotide excision repair (NER) by stabilizing XPA, a crucial deoxyribonucleic acid (DNA) repair protein. This stabilization occurred through OA's interaction with glucose-regulated protein 94 (GRP94), which disrupted murine double minute 2 (MDM2)-mediated XPA ubiquitination and proteasomal degradation. By maintaining XPA levels, OA expedited photoproduct clearance and diminished genomic instability, ultimately impeding NMSC development. These findings suggest OA as a promising chemopreventive agent targeting the GRP94/MDM2-XPA axis to counteract UVB-induced carcinogenesis.
Animals ; Ultraviolet Rays/adverse effects* ; Skin Neoplasms/prevention & control* ; Flavonoids/pharmacology* ; Mice ; Xeroderma Pigmentosum Group A Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-mdm2/genetics* ; DNA Repair/drug effects* ; Scutellaria baicalensis/chemistry* ; Mice, Hairless ; Skin/radiation effects*

Oroxylin A (OA) is a natural flavonoid primarily derived from the plants Oroxylum indicum and Scutellaria baicalensis. Currently, OA is obtainable through chemical synthesis and exhibits polypharmacological properties, including anti-cancer, anti-inflammatory, anti-microbial, and multi-organ protective effects. The first-in-class drug OA tablets are presently undergoing phase Ib/IIa clinical trials for hepatocellular carcinoma (HCC) treatment. Substantial evidence suggests that OA demonstrates therapeutic potential against various hepatic and gastrointestinal (GI) disorders, including HCC, hepatic fibrosis, fatty liver disease, hepatitis, liver injury, colitis, and colorectal cancer (CRC). OA exerts its therapeutic effects primarily by modulating several crucial signaling pathways, including those associated with apoptosis, oxidative stress, inflammation, glucolipid metabolism, and fibrosis activation. The oral pharmacokinetics of OA is characterized by phase II metabolism, hydrolysis, and enterohepatic recycling. This review provides a comprehensive overview of the critical stages involved in the development of OA tablets, presenting a holistic perspective on the progression of this first-in-class drug from preclinical to clinical phases. It encompasses the synthesis of active pharmaceutical ingredients, pharmacokinetics, pharmacological efficacy, toxicology, drug delivery, and recent advancements in clinical trials. Importantly, this review examines the potential mechanisms by which OA may influence the gut-liver axis, hypothesizing that these interactions may confer health benefits associated with OA that transcend the limitations posed by its poor bioavailability.
Humans ; Flavonoids/pharmacokinetics* ; Tablets ; Animals ; Gastrointestinal Diseases/drug therapy* ; Liver Diseases/drug therapy* ; Drug Development ; Clinical Trials as Topic ; Scutellaria baicalensis/chemistry*

This study aims to compare the metabolic differences of baicalin and its analogues between Shuganning Injection and Scutellariae Radix extract. Twelve SD rats were randomly divided into a Shuganning Injection group and a Scutellariae Radix extract group, with 6 rats in each group. Their liver microsomes were incubated with the drugs, and then the samples were collected. Ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) was used to analyze the prototype components and metabolites of the drugs in liver microsomes of each group. Another 12 SD rats were also divided into a Shuganning Injection group and a Scutellariae Radix extract group, with 6 rats in each group. The rats were administrated with 4.2 mL·kg~(-1) Shuganning Injection or Scutellariae Radix extract by tail vein injection. After 48 h, the rat urine, feces, and bile were collected, and UPLC-Q-Exactive Orbitrap-MS was used to analyze the prototype components and metabolites in each biological sample. The results showed that 5 prototype components and 8 metabolites of Shuganning Injection and Scutellariae Radix extract were identified in liver microsomes. A total of 5 prototype components were identified in rat urine, feces, and bile separately. Fifteen metabolites were identified in the urine, 9 metabolites in the feces, and 12 metabolites in the bile. The differences of metabolic pathways and number of metabolites of baicalin were compared between Shuganning Injection and Scutellariae Radix extract. For both Shuganning Injection and Scutellariae Radix extract, the metabolites of baicalin or baicalein in rat liver microsomes, urine, bile, and feces were mainly formed glucuronic acid conjugates, and there were a small amount of glucose conjugates and methylation products. Differences were found in the number and types of metabolites of baicalin in urine samples between Shuganning Injection and Scutellariae Radix extract, indicating that differences existed in metabolism between the two. This suggests that the other components in the formula lead to changes of metabolites in vivo.
Animals ; Rats ; Rats, Sprague-Dawley ; Microsomes, Liver/chemistry* ; Drugs, Chinese Herbal/administration & dosage* ; Feces/chemistry* ; Scutellaria baicalensis/chemistry* ; Male ; Bile/chemistry* ; Flavonoids/metabolism* ; Urine/chemistry* ; Chromatography, High Pressure Liquid ; Mass Spectrometry ; Plant Extracts

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*

The root of Scutellaria baicalensis Georgi, also called Huangqin, is frequently used in traditional Chinese medicine. In ancient China, S. baicalensis root was used to clear heat, protect the fetus, and avoid a miscarriage for thousands of years. In modern times, pregnancy-related diseases can seriously affect maternal and fetal health, but few systematic studies have explored the mechanisms and potential targets of S. baicalensis root in the treatment of pregnancy-related diseases. Flavonoids (baicalein, wogonin and oroxylin A) and flavonoid glycosides (baicalin and wogonoside) are the main chemical components in the root of S. baicalensis. This study presents the current understanding of the major chemical components in the root of S. baicalensis, focusing on their traditional uses, potential therapeutic effects and ethnopharmacological relevance to pregnancy-related disorders. The mechanisms, potential targets and experimental models of S. baicalensis root for ameliorating pregnancy-related diseases, such as recurrent spontaneous abortion, preeclampsia, preterm birth, fetal growth restriction and gestational diabetes mellitus, are highlighted.
Infant, Newborn ; Humans ; Pregnancy ; Female ; Scutellaria baicalensis ; Premature Birth/drug therapy* ; Flavonoids ; Plant Extracts/pharmacology* ; Medicine, Chinese Traditional ; Ethnopharmacology ; China

The aim of this study was to explore the effects of Huangqin Tang(HQT) on the NLRP3/Caspase-1 signaling pathway in mice with DSS-induced ulcerative colitis(UC). C57BL/6J mice were randomly divided into a blank group, a model group(DSS group), and low-, medium-and high-dose HQT groups(HQT-L, HQT-M, and HQT-H), and western medicine mesalazine group(western medicine group). The UC model was induced in mice. Subsequently, the mice in the HQT-L, HQT-M, HQT-H groups, and the western medicine group were given low-, medium-, high-dose HQT, and mesalazine suspension by gavage, respectively, while those in the blank and DSS groups were given an equal volume of distilled water by gavage. After 10 days of administration, the body weight, DAI scores, and colonic histopathological score of mice in each group were determined. The levels of IL-6, IL-10, IL-1β, and TNF-α in serum were determined by ELISA. The mRNA expression of NLRP3 and Caspase-1 in colon tissues was determined by RT-qPCR. The protein expression of NLRP3 and Caspase-1 in colon tissues was detected by immunohistochemistry. The results showed that compared with the blank group, the DSS group showed decreased body weight of mice and increased DAI scores and intestinal histopathological score. Compared with the DSS group, the HQT groups and the western medicine group showed improved DAI scores, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). The intestinal histopathological scores of the HQT groups and the western medicine group significantly decreased, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). In addition, compared with the blank group, the DSS group showed elevated expression of NLRP3 and Caspase-1 in colon tissues, increased serum levels of IL-6, IL-1β, and TNF-α, and decreased IL-10 level. Compared with the DSS group, the HQT groups and the western medicine group displayed decreased expression of NLRP3 and Caspase-1 in colon tissues, reduced serum levels of IL-6, IL-1β, and TNF-α, and increased IL-10 level. The improvement was the most significant in the HQT-H group and the western medicine group(P<0.01). In conclusion, HQT may reduce the expression of NLRP3 and Caspase-1 in colon tissues, reduce the se-rum levels of IL-6, IL-1β, and TNF-α, and increase the expression of IL-10 by regulating the classic pyroptosis pathway of NLRP3/Caspase-1, thereby improving the symptoms of intestinal injury and inflammatory infiltration of intestinal mucosa in DSS mice to achieve its therapeutic effect.
Animals ; Mice ; Caspase 1/genetics* ; Colitis, Ulcerative/genetics* ; Colon ; Dextran Sulfate/adverse effects* ; Disease Models, Animal ; Interleukin-10/genetics* ; Interleukin-6/genetics* ; Mesalamine/pharmacology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Scutellaria baicalensis/chemistry* ; Tumor Necrosis Factor-alpha/metabolism* ; Drugs, Chinese Herbal/pharmacology*

Viruses, the smallest microorganisms, continue to present an escalating threat to human health, being the leading cause of mortality worldwide. Over the decades, although significant progress has been made in the development of therapies and vaccines against viral diseases, the need for effective antiviral interventions remains urgent. This urgency stems from the lack of effective vaccines, the severe side effects associated with current drugs, and the emergence of drug-resistant viral strains. Natural plants, particularly traditionally-used herbs, are often considered an excellent source of medicinal drugs with potent antiviral efficacy, as well as a substantial safety profile. Scutellaria baicalensis, a traditional Chinese medicine, has garnered considerable attention due to its extensive investigation across diverse therapeutic areas and its demonstrated efficacy in both preclinical and clinical trials. In this review, we mainly focused on the potential antiviral activities of ingredients in Scutellaria baicalensis, shedding light on their underlying mechanisms of action and therapeutic applications in the treatment of viral infections.
Humans ; Antiviral Agents/therapeutic use* ; Scutellaria baicalensis ; Virus Diseases/drug therapy* ; Medicine, Chinese Traditional

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*