BACKGROUND: Scutellaria barbata D. Don (SB), commonly known as Ban Zhi Lian and firstly documented by Shigong Chen, is a dried whole plant that has been studied for its therapeutic effects on breast cancer, colon cancer, and prostate cancer. Among its various compounds, scutellarin (SCU) has been demonstrated with anti-tumor effects.
OBJECTIVE: This study aimed to evaluate the effects of SB water extract (SBW) and scutellarin on breast cancer stem cells (BCSCs), and to investigate their potential therapeutic effects on breast tumors in mice.
METHODS: BCSCs were enriched from human breast cancer cells (MDA-MB-231 and MDA-MB-361) and their characteristics were analyzed. The effects of varying concentrations of SBW and scutellarin on cell viability, proliferation, self-renewal, and migration abilities were studied, along with the underlying mechanisms. The in vivo anti-tumor effects of scutellarin were further evaluated in SCID/NOD mice. Firstly, mice were inoculated with naïve BCSCs and subjected to treatment with scutellarin or vehicle. Secondly, BCSCs were pre-treated with scutellarin or vehicle prior to inoculation into mice.
RESULTS: The derived BCSCs expressed CD44, CD133 and ALDH1, but not CD24, indicating that BCSCs have been successfully induced from both MDA-MB-231 and MDA-MB-361 cells. Both SBW and scutellarin reduced the viability, proliferation, sphere and colony formation, and migration of BCSCs. In mice with tumors derived from naïve BCSCs, scutellarin significantly reduced tumor growth, expression of proliferative (Ki67) and stem cell markers (CD44), and lung metastasis. In addition, pre-treatment with scutellarin also slowed tumor growth. Western blot results suggested the involvement of Wnt/β-catenin, NF-κB, and PTEN/Akt/mTOR signaling pathways underlying the inhibitory effects of scutellarin.
CONCLUSIONS: Our study demonstrated for the first time that both SB water extract and scutellarin could reduce the proliferation and migration of BCSCs in vitro. Scutellarin was shown to possess novel inhibitory activities in BCSCs progression. These findings suggest that Scutellaria barbata water extract, in particular, scutellarin, may have potential to be further developed as an adjuvant therapy for reducing breast cancer recurrence.

Scutellaria barbata D. Don 1825 is an important medicinal plant distributed in wetlands about 2000 m above sea level and used to treat various diseases. The complete chloroplast genome of S. barbata is 152,050 bp with four subregions consisting of a large single-copy region (84,053 bp), a small single-copy region (17,517 bp), and a pair of inverted repeats (25,240 bp). In the chloroplast genome of S. barbata, 131 genes were detected, comprising 87 protein-encoding genes, eight ribosomal RNA (rRNA) genes, and 36 transfer RNA (tRNA) genes. Phylogenetic analysis based on the complete chloroplast genome and protein-coding DNA sequences of 27 related taxa of the genus (out group included Holmskioldia sanguinea and Tinnea aethiopica) indicates that S. barbata was made a clade with S. orthocalyx, and S. meehanioides was a sister to them. The first chloroplast genome of S. barbata was reported in this work, serving as a potential reference for important medicinal plants within the Scutellaria genus.

BACKGROUND: Traditional Chinese medicines are widely used in cancer treatment. Scutellaria barbata and Hedyotis diffusa herb pair (SH) has an anticancer effects in various tumors. However, the specific mechanism of SH in breast cancer remains unclear.
METHODS: In the present research, we investigated the effect and regulatory network of SH in in breast cancer. CCK8, colony formation, transwell, wound healing and flow cytometry analysis were used for the detection of cell function.
RESULTS: Ethyl acetate fraction from SH at an equal weight ratio (EA11) could inhibit the proliferation, migration and invasion of MCF7 and MDA-MB-231 cells. It also induced apoptosis in these two cell lines by downregulating Bcl2 and upregulating Bax and Cleaved-Caspase3. SH reduced the activation of the AKT/mTOR signaling pathway and the expression of p70S6K. Sequencing results showed that LMO1 was significantly downregulated in SH-treated cells compared with control cells. Importantly, overexpression of LMO1 attenuated the inhibitory effect of SH on cell proliferation and invasion and induced inflammatory tumor microenvironment.
CONCLUSIONS: In conclusion, the SH herb pair inhibited the proliferation and metastasis through downregulating LMO1 expression and reducing the activation of the AKT/mTOR signaling pathway. LMO1 has the potential as a new target in the treatment of breast cancer.

OBJECTIVE: The present study aimed to investigate the therapeutic mechanism of Hedyotis diffusa Willd (HDW) and Scutellaria barbata (SB) in ccRCC using a combination of single-cell RNA sequencing (scRNA-seq) and network pharmacology.
METHODS: The active ingredients and potential molecular targets of HDW-SB were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Gene expression data (GSE53757) were obtained from the Gene Expression Omnibus database. The hub genes of HDW-SB against ccRCC were identified via the protein-protein interaction network, and further analyzed by molecular complex detection. The roles of these genes in the diagnosis and immune infiltration of ccRCC were analyzed. The clinical significance of hub genes was verified using scRNA-seq data (GSE121638) and molecular docking.
RESULTS: Following the PPI network analysis, 29 hub genes of HDW-SB against ccRCC were identified. All hub genes, except for CENPE, had significantly different expressions in tumor tissue and a more accurate diagnosis of ccRCC. Fifteen cell clusters were defined based on the scRNA-seq dataset, and the clusters were annotated as six cell types using marker genes. TYMS and KIAA0101 from hub genes were highly expressed in NK cells. Three active compounds, quercetin, luteolin, and baicalein, were found to target TYMS and KIAA0101 from the compound-target interaction network.
CONCLUSIONS: 29 hub genes of HDW-SB against ccRCC were identified and showed good performance in terms of diagnosis and prognosis. Moreover, among these hub genes docking with the main ingredients of HDW-SB, TYMS and KIAA0101 exerted anti-ccRCC effects through NK cells.

Scutellaria barbata is a traditional Chinese herb medicine and a major source of bioactive clerodane diterpenoids. However, barely clerodanes have been isolated from the closely related S. baicalensis. Here we assembled a chromosome-level genome of S. barbata and identified three class II clerodane diterpene synthases (SbarKPS1, SbarKPS2 and SbaiKPS1) from these two organisms. Using in vitro and in vivo assays, SbarKPS1 was characterized as a monofunctional (-)-kolavenyl diphosphate synthases ((-)-KPS), while SbarKPS2 and SbaiKPS1 produced major neo-cleroda-4(18),13E-dienyl diphosphate with small amount of (-)-KPP. SbarKPS1 and SbarKPS2 shared a high protein sequence identity and formed a tandem gene pair, indicating tandem duplication and sub-functionalization probably led to the evolution of monofunctional (-)-KPS in S. barbata. Additionally, SbarKPS1 and SbarKPS2 were primarily expressed in the leaves and flowers of S. barbata, which was consistent with the distribution of major clerodane diterpenoids scutebarbatine A and B. In contrast, SbaiKPS1 was barely expressed in any tissue of S. baicalensis. We further explored the downstream class I diTPS by functional characterizing of SbarKSL3 and SbarKSL4. Unfortunately, no dephosphorylated product was detected in the coupled assays with SbarKSL3/KSL4 and four class II diTPSs (SbarKPS1, SbarKPS2, SbarCPS2 and SbarCPS4) when a phosphatase inhibitor cocktail was included. Co-expression of SbarKSL3/KSL4 with class II diTPSs in yeast cells did not increase the yield of the corresponding dephosphorylated products, either. Together, these findings elucidated the involvement of two class II diTPSs in clerodane biosynthesis in S. barbata, while the class I diTPS is likely not responsible for the subsequent dephosphorylation step.

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Background: Hepatocellular carcinoma is one of the most common cancers with the characteristics of invasion and high mortality. Current forms of prevention remain severe. Scutellaria barbata is widely used in traditional Chinese medicine treatment of various tumors. This study explored the mechanism of Scutellaria barbata in the treatment of hepatocellular carcinoma by network pharmacology and bioinformatics. Methods: The active ingredients of Scutellaria barbata and potential targets for the treatment of hepatocellular carcinoma were collected by network pharmacology. The protein interaction network was constructed to screen the core targets, and the association between the core targets and diseases was further verified by bioinformatics methods. Finally, the active ingredients corresponding to the targets closely related to the disease were screened for AMDE characteristics analysis. Molecular docking of drug-like ingredients with corresponding targets was performed. We used CCK-8 kit to determine the effect of active ingredients on cell proliferation. Results: 29 candidate active ingredients and 461 related targets of Scutellaria barbata were screened. A total of 8238 potential therapeutic targets for hepatocellular carcinoma were indentified. Finally, 373 potential targets for the treatment of HCC were obtained. The active ingredients: wogonin, Rhamnazin, eriodictyol, quercetin, baicalein, and luteolin, etc. The core targets were CDK1, CDK4, SRC, and E2F1. A total of 3056 GO enrichment entries were obtained, and 180 enrichment results were obtained by KEGG pathway analysis. Genes were mainly enriched in PI3K-Akt signaling pathway, IL-17 signaling pathway, TNF signaling pathway, apoptosis pathway, and hepatocellular carcinoma pathway. Molecular docking results showed that the screened compounds had strong binding ability with the corresponding target proteins. CCK8 assays showed that Rhamnazin and Luteolin suppressed the proliferation of HCC cells significantly compared with controls. Conclusion: This study revealed that the mechanism of Scutellaria barbata in the treatment of hepatocellular carcinoma may be that the active ingredients inhibit the expression of core genes and block the PI3K-AKT signaling pathway to inhibit the proliferation, and migration and induce apoptosis of cancer cells.

The presence of anticancer clerodane diterpenoids is a chemotaxonomic marker for the traditional Chinese medicinal plant Scutellaria barbata, although the molecular mechanisms behind clerodane biosynthesis are unknown. Here, we report a high-quality assembly of the 414.98 Mb genome of S. barbata into 13 pseudochromosomes. Using phylogenomic and biochemical data, we mapped the plastidial metabolism of kaurene (gibberellins), abietane, and clerodane diterpenes in three species of the family Lamiaceae (Scutellaria barbata, Scutellaria baicalensis, and Salvia splendens), facilitating the identification of genes involved in the biosynthesis of the clerodanes, kolavenol, and isokolavenol. We show that clerodane biosynthesis evolved through recruitment and neofunctionalization of genes from gibberellin and abietane metabolism. Despite the assumed monophyletic origin of clerodane biosynthesis, which is widespread in species of the Lamiaceae, our data show distinct evolutionary lineages and suggest polyphyletic origins of clerodane biosynthesis in the family Lamiaceae. Our study not only provides significant insights into the evolution of clerodane biosynthetic pathways in the mint family, Lamiaceae, but also will facilitate the production of anticancer clerodanes through future metabolic engineering efforts.

Diterpenoids are considered the major bioactive components in Scutellaria barbata to treat cancer and inflammation, but few comprehensive profiling studies of diterpenoids have been reported. Herein, a stepwise diagnostic product ions (DPIs) filtering strategy for efficient and targeted profiling of diterpenoids in Scutellaria barbata was developed using UHPLC-Q-Exactive-Orbitrap-MS. After UHPLC-HRMS/MS analysis of six diterpenoid reference standards, fragmentation behaviors of these references were studied to provide DPIs. Then, stepwise DPIs filtering aimed to reduce the potential interferences of matrix ions and achieve more chromatographic peaks was conducted to rapidly screen the diterpenoids. The results demonstrated that stepwise DPIs were capable of simplifying the workload in data post-processing and the effective acquisition of low abundance compounds. Subsequently, DPIs and MS/MS fragment patterns were adopted to identify the targeted diterpenoids. As a result, 381 diterpenoids were unambiguously or tentatively identified, while 141 of them with completely new molecular weights were potential new diterpenoids for Scutellaria barbata. These results demonstrate that the developed stepwise DPIs filtering method could be employed as an efficient, reliable, and valuable strategy to screen and identify the diterpenoid profile in Scutellaria barbata. This might accelerate and simplify target constituent profiling from traditional Chinese medicine (TCM) extracts.

(1) Background: Candidiasis is a fungal infectious disease caused by opportunistic Candida species. The incidence of candidiasis has improved, due to prolonged antibiotic therapy and an increased number of immunocompromised patients. The purpose of this study was to evaluate if decoctions and essential oil (EO) of neem (Azadirachta indica, Meliaceae family), coptidis (Coptis chinensis, Ranunculaceae family), magnolia (Magnolia officinalis, Magnoliaceae family), scutellaria (Scutellaria barbata, Lamiaceae family), and the EO of manuka (Leptospermum scoparium, Myrtaceae family), have antifungal activity in vitro against some clinically prevalent species of Candida. (2) Methods: The antifungal activity was studied by the determination of the minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC) against five Candida strains. The effect in dimorphic transition of Candida albicans was also evaluated for the two plants with higher antimicrobial behavior. (3) Results: C. chinensis decoction and EO and L. scoparium EO exhibited antifungal activity in Candida spp. In addition to the fact that both C. chinensis decoction and EO proved strong antifungal activity, L. scoparium EO also displayed a relevant inhibitory effect on the dimorphic transition. (4) Conclusions: The results provided support for the potential use of C. chinensis and L. scoparium in the treatment of infections by Candida spp.