Ethanolic extract from Sophora moorcroftiana inhibit cell proliferation and alter the mechanical properties of human cervical cancer.

BACKGROUND: Cervical cancer is one of the most common gynecological malignancies. Previous studies have shown that the ethanol extract of Sophora moorcroftiana seeds (EESMS) possesses an antiproliferative effect on several tumors in vitro. Therefore, in this study, we assessed the impact of EESMS on human cervical carcinoma (HeLa) cell proliferation. METHODS: The proliferation and apoptotic effects of HeLa cells treated with EESMS were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay, dual acridine orange/ethidium bromide double staining, flow cytometry, and western blotting. Single-cell level atomic force microscopy (AFM) was conducted to detect the mechanical properties of HeLa cells, and proteomics and bioinformatics methods were used to elucidate the molecular mechanisms of EESMS. RESULTS: EESMS treatment inhibited HeLa cell proliferation by blocking the G0/G1 phase, increasing the expression of Caspase-3 and affecting its mechanical properties, and the EESMS indicated no significant inhibitory effect on mouse fibroblasts L929 cell line. In total, 218 differentially expressed proteins were identified using two-dimensional electrophoresis, and eight differentially expressed proteins were successfully identified using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. The differentially expressed proteins were involved in various cellular and biological processes. CONCLUSION: This study provides a perspective on how cells change through biomechanics and a further theoretical foundation for the future application of Sophora moorcroftiana as a novel low-toxicity chemotherapy medication for treating human cervical cancer.

Efficacy and Safety of Compound Kushen Injection for Advanced Colorectal Cancer: A Systematic Review and Meta-Analysis of Randomized Clinical Trials with Trial Sequential Analysis.

BACKGROUNDS: Colorectal cancer (CRC) is one of the common malignant tumors, with a gradually increasing incidence. Due to late detection and poor sensitivity to chemotherapy, it has become a difficult problem in tumor prevention and treatment at present. Exploring or discovering new combinations is a significant strategy for the treatment of CRC. Compound kushen injection (CKI) is a traditional Chinese medicine injection extracted from Sophora flavescens Ait. and Smilax glabra Roxb., which is widely used in the comprehensive treatment of CRC in China. This systematic review is aimed to ascertain the clinical efficacy and safety of CKI combined with chemotherapy in the treatment of advanced CRC based on available data. On this basis, the specific application of CKI in combination with chemotherapy in clinical practice is further discussed. METHODS: PubMed, Web of Science, the Cochrane Library, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Wanfang Database, Chinese Biomedicine Database Searches, the Chinese Clinical Trial Registry, and ClinicalTrials.gov were searched systematically, from inception to April 20, 2024. We adopted the ROB2 tool to assess quality of the included trials, Stata 16 for data analysis, and evaluated the publication bias with the funnel plot and Egger's test. The quality of the evidence was justified according to GRADE. We also used trial sequential analysis (TSA) to calculate the final required sample size in this meta-analysis and to verify whether the results present a reliable conclusion. The protocol for this systematic review was registered on PROSPERO (CRD42022380106) and has been published. RESULTS: Sixteen trials that examined 1378 patients were included in this study. Meta-analysis revealed that compared with chemotherapy, objective response rate (ORR, RR = 1.30, 95% CI: 1.18-1.44), disease control rate (DCR, RR = 1.08, 95% CI: 1.03-1.13), and KPS score improvement rate were improved (RR = 1.18, 95% CI: 1.07-1.31) by the combination of CKI and chemotherapy in patients with advanced CRC. Additionally, CKI combined with chemotherapy was associated with lower adverse reactions such as leukopenia (RR = 0.74, 95% CI: 0.62-0.87), thrombocytopenia (RR = 0.68, 95% CI: 0.49-0.94), gastrointestinal reactions (RR = 0.72, 95% CI: 0.55-0.94), and liver damage (RR = 0.48, 95% CI: 0.30-0.79), higher CD4+ ratio (MD = 9.70, 95% CI:8.73-10.68) and CD4+/CD8+ ratio (MD = 0.25, 95% CI: 0.22-0.28), and lower CD8+ T cell ratio (MD = -5.25, 95% CI: -5.94 to -4.56). Subgroup analysis demonstrated that ORR and DCR in patients with advanced CRC were improved when CKI combined with FOLFOX and 5Fu + L-OHP. Both 15 and 20 ml/day of CKI combined with FOLFOX provided a significant effect in ORR. Moreover, ORR was improved when the accumulated CKI dose reached 280 ml per course and 420 ml in total. 7 days/course as well as 14 days/course of CKI combined with FOLFOX were effective durations in ORR. As for DCR, 7 days/course of CKI combined with FOLFOX could improve efficacy. Furthermore, CKI + FOLFOX may be useful in ORR and DCR for at least 4 cycles of combination therapies. The TSA showed that firm results in ORR and DCR were established and additional trials were unlikely to change the results. CONCLUSION: CKI combined with chemotherapy provides a statistically significant and clinically important effect in the improvement of ORR, DCR, performance status, ADR reduction, and immune function in patients with CRC. However, more rigorously designed, large-scale, and multi-center RCTs are needed in the future.

Beneficial effects of oxymatrine from Sophora flavescens on alleviating Ulcerative colitis by improving inflammation and ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora flavescens is often used in traditional Chinese medicine for skin issues, diarrhea, and vaginal itching (Plant names have been checked with http://www.the/plant/list.org on Feb 22nd, 2024). Oxymatrine (OY), a major bioactive compound from Sophora flavescens, is commonly used in China to treat ulcerative colitis, but its mechanisms are still unclear. AIM OF THE STUDY: Recent studies have found that the crosstalk between ferroptosis and inflammation is an important mechanism in the pathogenesis of UC. The aim of this study was to investigate the potential underlying mechanisms of OY treatment on DSS-induced ulcerative colitis, specifically focusing on the processes of ferroptosis and inflammation. MATERIALS AND METHODS: Bioinformatics methods were used to identify key targets of OY for ferroptosis and inflammation in ulcerative colitis, based on GEO data and FerrDb database. Then, 4% DSS solution was used to induce UC model. OY's impact on morphological changes was assessed using colon views, Hematoxylin and eosin (HE) staining, and transmission electron microscopy (TEM). Ferroptosis phenotype index and inflammations factors were detected by ELISA or chem-bio detection kits. The screen out hub related genes about ferroptosis and inflammation were verified by RT-PCR, immunohistochemistry (IHC), and western blotting (WB) respectively. RESULTS: Bioinformatics results show that there are 16 key target genes involved in ferroptosis and inflammation interaction of OY treatment for UC, such as IL6, NOS2, IDO1, SOCS1, and DUOX. The results of animal experiments show that OY could depress inflammatory factors (IL-1ß, IL-6, TNF-α, HMGB1, and NLRP3) and reduce iron deposition (Fe2+, GSH). Additionally, OY suppressed the hub genes or proteins expression involved in ferroptosis and inflammation, including IL-1ß, IL-6, NOS2, HIF1A, IDO1, TIMP1, and DUOX2. CONCLUSION: This present study combines bioinformatics, molecular biology, and animal experimental research evidently demonstrated that OY attenuates UC by improving ferroptosis and inflammation, mainly target to the expression of IL-1ß, IL-6, NOS2, HIF1A, IDO1, TIMP1, and DUOX2.

QSAR prediction, synthesis, anticancer evaluation, and mechanistic investigations of novel sophoridine derivatives as topoisomerase I inhibitors.

Sophoridine, which is derived from the Leguminous plant Sophora alopecuroides L., has certain pharmacological activity as a new anticancer drug. Herein, a series of novel N-substituted sophoridine derivatives was designed, synthesized and evaluated with anticancer activity. Through QSAR prediction models, it was discovered that the introduction of a benzene ring as a main pharmacophore and reintroduced into a benzene in para position on the phenyl ring in the novel sophoridine derivatives improved the anticancer activity effectively. In vitro, 28 novel compounds were evaluated for anticancer activity against four human tumor cell lines (A549, CNE-2, HepG-2, and HEC-1-B). In particular, Compound 26 exhibited remarkable inhibitory effects, with an IC50 value of 15.6 µM against HepG-2 cells, surpassing cis-Dichlorodiamineplatinum (II). Molecular docking studies verified that the derivatives exhibit stronger binding affinity with DNA topoisomerase I compared to sophoridine. In addition, 26 demonstrated significant inhibition of DNA Topoisomerase I and could arrest cells in G0/G1 phase. This study provides valuable insights into the design and synthesis of N-substituted sophoridine derivatives with anticancer activity.

Compound sophora decoction alleviates ulcerative colitis by regulating macrophage polarization through cGAS inhibition: network pharmacology and experimental validation.

INTRODUCTION: Ulcerative colitis (UC) is a refractory disease with complex pathogenesis, and its pathogenesis is not clear. The present study aimed to investigate the potential target and related mechanism of Compound Sophora Decoction (CSD) in treating UC. METHODS: A network pharmacology approach predicted the components and targets of CSD to treat UC, and cell and animal experiments confirmed the findings of the approach and a new target for CSD treatment of UC. RESULTS: A total of 155 potential targets were identified for CSD treatment of UC, with some related to macrophage polarization, such as nitric oxide synthase (NOS2), also known as inducible nitric oxide synthase (iNOS). GO and KEGG enrichment analysis indicated that oxidative stress response and multiple inflammatory signaling pathways such as TNF-α may play a significant role. In vitro experiments revealed that Interferon-stimulated DNA (ISD) interference can cause polarization imbalances in Raw 264.7 and bone marrow-derived macrophages (BMDMs). Flow cytometry demonstrated that polarization of macrophages in the intestine, spleen, and lymph nodes in vivo was also unbalanced after dextran sulfate sodium (DSS) modeling with pathological intestinal injury. Both in vitro and in vivo studies indicated that after inducing inflammation, the levels of macrophage polarization-related markers (iNOS and Arg1) and inflammation-related factors (CCL17, IL10, TNF-α, and CXCL10) changed, accompanied by increased expression of cGAS. However, CSD treatment based on inflammation can inhibit the expression of cGAS protein and mRNA, lower the level of inflammatory factors, promote the expression of anti-inflammatory factors, and regulate macrophage polarization. CONCLUSION: We concluded that CSD alleviated DSS-induced UC by inhibiting cGAS, thus regulating macrophage polarization.

Radix Sophorae Flavescentis of Sophora flavescens Aiton inhibits LPS-induced macrophage pro-inflammatory response via regulating CFHR2 expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Long-term chronic inflammation often leads to chronic diseases. Although Sophora flavescens has been shown to have anti-inflammatory properties, its detailed molecular mechanism is still unknown. AIM OF STUDY: This study investigated the effect of Radix Sophorae Flavescentis on the LPS-induced inflammatory response in macrophages. MATERIALS AND METHODS: LPS was used to induce the peritoneal macrophages to simulate the inflammatory environment in vitro. Different concentrations of Radix Sophorae Flavescentis-containing (medicated) serum were used for intervention. The peritoneal macrophages were identified by using hematoxylin-eosin and immunofluorescence staining. ELISA was used to measure the TNF-α and IL-6 expression to determine the concentration of LPS. ELISA and Western blot (WB) were used to detect the PGE2 and CFHR2 expression in each group, respectively. The lentiviral vector for interference and overexpression of the CFHR2 gene was constructed, packaged, and transfected into LPS-induced macrophages. The transfection efficiency was verified by WB. Then, ELISA was used to detect the TNF-α, PGE2, and IL-6 expression. WB was used to detect the CFHR2, iNOS, COX-2, TLR2, TLR4, IFN-γ, STAT1, and p-STAT1 expression. RESULTS: The primary isolated cells were identified as macrophages. The LPS-treated macrophages exhibited significantly higher expression of PGE2 and CFHR2, and the inflammatory factors TNF-α and IL-6, as well as iNOS, COX-2, TLR2, TLR4, IFN-γ, STAT1, and p-STAT1 expression compared with the control group (P < 0.05). The TNF-α, PGE2, and IL-6 levels, as well as CFHR2, iNOS, COX-2, TLR2, TLR4, IFN-γ, STAT1, and p-STAT1 expression were considerably lower in the LPS-induced+10% medicated-serum group, LPS-induced+20% medicated-serum group, and shCFHR interference group compared with the LPS group (P < 0.05). CONCLUSION: Radix Sophorae Flavescentis might mediate CFHR2 expression and play an important role in inhibiting the LPS-induced pro-inflammatory response of macrophages. Radix Sophorae Flavescentis could be a potential treatment for LPS-induced related inflammatory diseases.

Isoprenoid flavonoids isolated from Sophora davidii and their activities induces apoptosis and autophagy in HT29 cells.

Four previously undescribed isoprenoid flavonoids (2-5) were isolated from Sophora davidii, along with five known analogues. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR, and absolute configurations determined by theoretical calculations, including ECD and NMR calculation. The cytotoxic effects of the isolated compounds on human HT29 colon cancer cells were evaluated using the MTT assay, compound 1 exhibited cytotoxicity against human HT29 colon cancer cells with an IC50 value of 8.39 ± 0.09 µM. Studies conducted with compound 1 in HT29 cells demonstrated that it may induce apoptosis and autophagy in HT29 by promoting the phosphorylation of P38 MAPK and inhibiting the phosphorylation of Erk MAPK.

Aloperine-Type Alkaloids with Antiviral and Antifungal Activities from the Seeds of Sophora alopecuroides L.

As a continuous flow investigation of novel pesticides from natural quinolizidine alkaloids, the chemical compositions of the seeds of Sophora alopecuroides were thoroughly researched. Fifteen new aloperine-type alkaloids (1-15) as well as six known aloperine-type alkaloids (16-21) were obtained from the extract of S. alopecuroides. The structures of 1-21 were confirmed via HRESIMS, NMR, UV, IR, ECD calculations, and X-ray diffraction. The antiviral activities of 1-21 against tobacco mosaic virus (TMV) were detected following the improved method of half-leaf. Compared with ningnanmycin (protective: 69.7% and curative: 64.3%), 15 exhibited excellent protective (71.7%) and curative (64.6%) activities against TMV. Further biological studies illustrated that 15 significantly inhibited the transcription of the TMV-CP gene and increased the activities of polyphenol oxidase (PPO), peroxidase (POD), superoxide dismutase (SOD), and phenylalanine ammonia-lyase (PAL). The antifungal activities of 1-21 against Phytophythora capsica, Botrytis cinerea, Alternaria alternata, and Gibberella zeae were screened according to a mycelial inhibition test. Compound 13 displayed excellent antifungal activity against B. cinerea (EC50: 7.38 µg/mL). Moreover, in vitro antifungal mechanism studies displayed that 13 causes accumulation of reactive oxygen species and finally leads to mycelia cell membrane damage and cell death in vitro.

Multi-omics and chemical profiling approaches to understand the material foundation and pharmacological mechanism of sophorae tonkinensis radix et rhizome-induced liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophorae tonkinensis Radix et Rhizoma (STR) is an extensively applied traditional Chinese medicine (TCM) in southwest China. However, its clinical application is relatively limited due to its hepatotoxicity effects. AIM OF THE STUDY: To understand the material foundation and liver injury mechanism of STR. MATERIALS AND METHODS: Chemical compositions in STR and its prototypes in mice were profiled by ultra-performance liquid chromatography coupled quadrupole-time of flight mass spectrometry (UPLC-Q/TOF MS). STR-induced liver injury (SILI) was comprehensively evaluated by STR-treated mice mode. The histopathologic and biochemical analyses were performed to evaluate liver injury levels. Subsequently, network pharmacology and multi-omics were used to analyze the potential mechanism of SILI in vivo. And the target genes were further verified by Western blot. RESULTS: A total of 152 compounds were identified or tentatively characterized in STR, including 29 alkaloids, 21 organic acids, 75 flavonoids, 1 quinone, and 26 other types. Among them, 19 components were presented in STR-medicated serum. The histopathologic and biochemical analysis revealed that hepatic injury occurred after 4 weeks of intragastric administration of STR. Network pharmacology analysis revealed that IL6, TNF, STAT3, etc. were the main core targets, and the bile secretion might play a key role in SILI. The metabolic pathways such as taurine and hypotaurine metabolism, purine metabolism, and vitamin B6 metabolism were identified in the STR exposed groups. Among them, taurine, hypotaurine, hypoxanthine, pyridoxal, and 4-pyridoxate were selected based on their high impact value and potential biological function in the process of liver injury post STR treatment. CONCLUSIONS: The mechanism and material foundation of SILI were revealed and profiled by a multi-omics strategy combined with network pharmacology and chemical profiling. Meanwhile, new insights were taken into understand the pathological mechanism of SILI.

Effects of acid and aluminum stress on seed germination and physiological characteristics of seedling growth in Sophora davidii.

Sophora davidii, a vital forage species, predominantly thrives in the subtropical karst mountains of Southwest China. Its resilience to poor soil conditions and arid environments renders it an ideal pioneer species for ecological restoration in these regions. This study investigates the influence of acidic, aluminum-rich local soil on the germination and seedling growth physiology of S. davidii. Experiments were conducted under varying degrees of acidity and aluminum stress, employing three pH levels (3.5 to 5.5) and four aluminum concentrations (0.5 to 2.0 mmol·L-1). The results showed that germination rate, germination index, and vigor index of S. davidii seeds were decreased but not significantly under slightly acidic conditions (pH 4.5-5.5), while strong acid (pH = 3.5) significantly inhibited the germination rate, germination index, and vigor index of white spurge seeds compared with the control group. Aluminum stress (≥0.5 mmol·L-1) significantly inhibited the germination rate, germination index, and vigor index of S. davidii seed. Moreover, the seedlings' root systems were sensitive to the changes of aluminum concentration, evident from significant root growth inhibition, characterized by root shortening and color deepening. Notably, under aluminum stress (pH = 4.3), the levels of malondialdehyde and proline in S. davidii escalated with increasing aluminum concentration, while antioxidant enzyme activities demonstrated an initial increase followed by a decline. The study underscores the pivotal role of cellular osmoregulatory substances and protective enzymes in combating aluminum toxicity in S. davidii, a key factor exacerbating growth inhibition in acidic environments. These findings offer preliminary theoretical insights for the practical agricultural utilization of S. davidii in challenging soil conditions.

Estrogenic Prenylated Flavonoids in Sophora flavescens.

Sophora flavescens is a medicinal herb distributed widely in Japan and it has been used to treat various diseases and symptoms. To explore its pharmacological use, we examined the estrogenic activity of four prenylated flavonoids, namely kurarinone, kushenols A and I, and sophoraflavanone G, which are characterized by the lavandulyl group at position 8 of ring A, but have variations in the hydroxyl group at positions 3 (ring C), 5 (ring A) and 4' (ring B). These prenylated flavonoids were examined via cell proliferation assays using sulforhodamine B, Western blotting, and RT-PCR, corresponding to cell, protein, and transcription assays, respectively, based on estrogen action mechanisms. All the assays employed here found weak but clear estrogenic activities for the prenylated flavonoids examined. Furthermore, the activities were inhibited by an estrogen receptor antagonist, suggesting that the activities were likely being mediated by the estrogen receptors. However, there were differences in the activity, attributable to the hydroxyl group at position 4', which is absent in kushenol A. While the estrogenic activity of kurarinone and sophoraflavanone G has been reported before, to the best of our knowledge, there are no such reports on kushenols A and I. Therefore, this study represents the first report of their estrogenic activity.

The anti-inflammatory activity of flavonoids and alkaloids from Sophora flavescens alleviates psoriasiform lesions: Prenylation and methoxylation beneficially enhance bioactivity and skin targeting.

The herb Sophora flavescens displays anti-inflammatory activity and can provide a source of antipsoriatic medications. We aimed to evaluate whether S. flavescens extracts and compounds can relieve psoriasiform inflammation. The ability of flavonoids (maackiain, sophoraflavanone G, leachianone A) and alkaloids (matrine, oxymatrine) isolated from S. flavescens to inhibit production of cytokine/chemokines was examined in keratinocytes and macrophages. Physicochemical properties and skin absorption were determined by in silico molecular modeling and the in vitro permeation test (IVPT) to establish the structure-permeation relationship (SPR). The ethyl acetate extract exhibited higher inhibition of interleukin (IL)-6, IL-8, and CXCL1 production in tumor necrosis factor-α-stimulated keratinocytes compared to the ethanol and water extracts. The flavonoids demonstrated higher cytokine/chemokine inhibition than alkaloids, with the prenylated flavanones (sophoraflavanone G, leachianone A) led to the highest suppression. Flavonoids exerted anti-inflammatory effects via the extracellular signal-regulated kinase, p38, activator protein-1, and nuclear factor-κB signaling pathways. In the IVPT, prenylation of the flavanone skeleton significantly promoted skin absorption from 0.01 to 0.22 nmol/mg (sophoraflavanone G vs. eriodictyol). Further methoxylation of a prenylated flavanone (leachianone A) elevated skin absorption to 2.65 nmol/mg. Topical leachianone A reduced the epidermal thickness in IMQ-treated mice by 47%, and inhibited cutaneous scaling and cytokine/chemokine overexpression at comparable levels to a commercial betamethasone product. Thus, prenylation and methoxylation of S. flavescens flavanones may enable the design of novel antipsoriatic agents.

Isolation and Characterization of Antimicrobial Metabolites from the Sophora tonkinensis-Associated Fungus Penicillium sp. GDGJ-N37.

Chemical investigation of Penicillium sp. GDGJ-N37, a Sophora tonkinensis-associated fungus, yielded two new azaphilone derivatives, N-isoamylsclerotiorinamine (1) and 7-methoxyl-N-isoamylsclerotiorinamine (2), and four known azaphilones (3-6), together with two new chromone derivatives, penithochromones X and Y (7 and 8). Their structures were elucidated based on spectroscopic data, CD spectrum, and semi-synthesis. Sclerotioramine (3) showed significant antibacterial activities against B. subtilis and S. dysentery, and it also showed most potent anti-plant pathogenic fungi activities against P. theae, C. miyabeanus, and E. turcicum.

Kaistella yananensis sp. nov., a Novel Indoleacetic Acid-Producing Bacterium Isolated from the Root Nodules of Sophora davidii (Franch.) Skeels.

A novel endophytic bacterium, designated strain BT6-1-3T, was isolated from the root nodules of a leguminous shrub named Sophora davidii (Franch.) Skeels, found growing wild in Yan'an, Shaanxi Province, China. Cells were Gram-staining-negative, non-motile, catalase-positive, oxidase-positive, and did not produce H2S. Strain BT6-1-3T grew at 15-40 °C (optimum 30 °C), at pH 6.0-10.0 (optimum pH 9.0), and with 0-1% (w/v) NaCl (optimum 0.5%). The quinone system was menaquinone 6. The major fatty acids present in BT6-1-3T were iso-C11:0, iso-C15:0, and C16:0. The G+C content of genomic DNA was 39.4 mol% by whole genome sequencing. According to the analysis of 16S rRNA gene sequence, the closest relative was Kaistella montana WG4 (nucleotide identity was 97.6%). The genome of strain BT6-1-3T was sequenced, and the genome similarity was calculated using average nucleotide identity and genome-to-genome distance analysis with the genomes of other strains of Kaistella. Both strongly supported that the strain BT6-1-3T belonged to the genus Kaistella as a representative of a new species. Based on phylogenetic analysis, chemotaxonomic data, and physiological and biochemical characteristics, strain BT6-1-3T represents a new species of the genus Kaistella and is named as Kaistella yananensis sp. nov. Type strain is BT6-1-3T (= NBRC 115452T = CGMCC 1.60032T).

Mechanisms predictive of Tibetan Medicine Sophora moorcroftiana alkaloids for treatment of lung cancer based on the network pharmacology and molecular docking.

BACKGROUND: Leguminous Sophora moorcroftiana (SM) is a genuine medicinal material in Tibet. Many research results have reveal the Sophora moorcroftiana alkaloids (SMA), as the main active substance, have a wide range of effects, such as antibacterial, antitumor and antiparasitic effects. However, there are few reports on the inhibition of lung cancer (LC) and its inhibitory mechanism, and the pharmacological mechanism of SMA is still unclear, Therefore, exploring its mechanism of action is of great significance. METHODS: The SMA active components were obtained from the literature database. Whereas the corresponding targets were screened from the PubChem and PharmMapper database, UniProt database were conducted the correction and transformation of UniProt ID on the obtained targets. The GeneCards and OMIM databases identified targets associated with LC. Venny tools obtained the intersection targets of SMA and LC. R language and Cytoscape software constructed the visual of SMA - intersection targets - LC disease network. The intersection targets protein-protein interaction (PPI) network were built by the STRING database. The functions and pathways of the common targets of SMA and LC were enriched by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking And A549 cells vitro experiment were performed to further validate our finding. RESULTS: We obtained six kinds of alkaloids in SM, 635 potential targets for these compounds, and 1,303 genes related to LC. SMA and LC intersection targets was 33, including ALB, CCND1, ESR1, NOTCH1 and AR. GO enrichment indicated that biological process of SMA was mainly involved in the positive regulation of transcription and nitric oxide biosynthetic process, and DNA-templated, etc. Biological functions were mainly involved in transcription factor binding and enzyme binding, etc. Cell components were mainly involved in protein complexes, extracellular exosome, cytoplasm and nuclear chromatin, etc., Which may be associated with its anti-LC effects. KEGG enrichment analysis showed that main pathways involved in the anti-LC effects of SMA, including pathway in cancer, non small-cell lung cancer, p53, PI3K-Akt and FOXO signaling pathways. Molecular docking analyses revealed that the six active compounds had a good binding activity with the main therapeutic targets 2W96, 2CCH and 1O96. Experiments in vitro proved that SMA inhibited the proliferation of LC A549 cells. CONCLUSIONS: Results of the present study, we have successfully revealed the SMA compounds had a multi-target and multi-channel regulatory mechanism in treatment LC, These findings provided a solid theoretical reference of SMA in the clinical treatment of LC.

Community ecological succession of endophytic fungi associates with medicinal compound accumulation in Sophora alopecuroides.

Endophytic fungi of medicinal plants are symbiotic with the host and play an important role in determining metabolites. To understand the relationship between the accumulation of Sophora alopecuroides' medicinal bioactive compounds and the ecological succession of endophytic fungi, here we collected samples from S. alopecuroides at four developmental stages (adult, flowering, podding, and mature) and different organs (roots, stems, leaves, and seeds) at the mature stage. We then used high-performance liquid chromatography-mass spectrometry and high-throughput sequencing on the internal transcribed spacer region to identify the medicinal compounds and endophytic fungal communities in each sample. The endophytic fungal community characteristics and accumulation of medicinally bioactive compounds of S. alopecuroides varied with the host's developmental stages and organs, with the highest total alkaloids content of 111.9 mg/g at the mature stage. Membership analysis and network connection analysis showed a total of 15 core endophytic fungi in different developmental stages and 16 core endophytic fungi in different organs at the mature stage. The unclassified Ascomycota, Aspergillus, and Alternaria were significantly and positively correlated with the medicinal compounds of S. alopecuroides at the mature stage (r > 0.6 or r < -0.6; P < 0.05). In this study, we identified key endophytic fungal resources that affect the content of medicinally bioactive compounds in S. alopecuroides. This discovery could lay the foundation for enhancing the yield of medicinally bioactive compounds in S. alopecuroides and the development and application of functional endophytic fungi.IMPORTANCESophora alopecuroides is a traditional Chinese herbal medicine. The major medicinal chemicals are considered to be quinolizidine alkaloids. Quinolizidine alkaloids have been widely used for the treatment of tumors, dysentery, and enteritis. Previous studies have found that endophytic fungi in S. alopecuroides can promote the accumulation of host quinolizidine alkaloids. However, the relationship between the accumulation of S. alopecuroides' medicinal bioactive compounds and the ecological succession of endophytic fungi remains unclear. In this study, we screened the key endophytic fungal resources affecting the content of medicinally bioactive compounds and laid the foundation for subsequent research on the mechanism by which endophytic fungi promote the accumulation of medicinally bioactive compounds in S. alopecuroides.

Three new quinolizidine alkaloids from the roots of Sophora tonkinensis.

Three new quinolizidine alkaloids (1 - 3), including one new naturally isoflavone and cytisine polymer (3), along with 6 known ones were isolated from the ethanol extract of Sophora tonkinensis Gagnep. Their structures were elucidated by comprehensive spectroscopic data analysis (IR, UV, HRESIMS, 1D and 2D NMR), combined with ECD calculations. The antifungal activity against Phytophythora capsica, Botrytis cinerea, Gibberella zeae, and Alternaria alternata of the compounds was evaluated in a mycelial inhibition assay. Biological tests indicated that compound 3 exhibited strong antifungal activity against P. capsica with EC50 values of 17.7 µg/ml.

Characteristics of chloroplast and mitochondrial genomes and intracellular gene transfer in the Korean endemic shrub, Sophora koreensis Nakai (Fabaceae).

Sophora koreensis Nakai, an endemic species distributed only in the Korean Peninsula, is of great geographical, economic, and taxonomic importance. Although its complete chloroplast (cp) genome sequence has been reported, its mitochondrial (mt) genome sequence has not yet been studied. Therefore, in this study, we aimed to investigate its mt genome sequence and compare it with those reported for other Fabaceae species. Total genomic DNA was extracted from fresh S. koreensis leaves collected from natural habitats in Gangwon-do Province, South Korea. This was followed by polymerase chain reaction (PCR) amplification of cpDNA insertions in the mt genome and the detection of microsatellites and dispersed repeats in the cp and mt genomes. Finally, the cp and mt genomes of S. koreensis were compared with those reported for other Fabaceae species. The cp sequence of S. koreensis showed identical gene orders and contents as those previously reported. Only six substitutions and one deletion were detected with 99 % homology. Conversely, the complete mt genome sequence, which was 517,845 bp in length and encoded 61 genes, including 43 protein-coding, 15 transfer RNAs, and 3 ribosomal RNA genes, was considerably different from that of S. japonica in terms of gene order and composition. Further, the mt genome of S. koreensis included ca. 7 and 3 kb insertions, representing an intracellular gene transfer (IGT) event, and the regions with these insertions were determined to be originally present in the cp genome. This IGT event was also confirmed via PCR amplification. IGT events can be induced via biological gene expression control or the use of repetitive sequences, and they provide important insights into the evolutionary lineage of S. koreensis. However, further studies are needed to clarify the gene transfer mechanisms between the two organelles.

Sophora tonkinensis and active compounds inhibit mitochondrial impairments, inflammation, and LDLR deficiency in myocardial ischemia mice through regulating the vesicle-mediated transport pathway.

Ancient Chinese medicine literature and modern pharmacological studies show that Sophora tonkinensis Gagnep. (ST) has a protective effect on the heart. A biolabel research based on omics and bioinformatics and experimental validation were used to explore the application value of ST in the treatment of heart diseases. Therapeutic potential, mechanism of action, and material basis of ST in treating heart diseases were analyzed by proteomics, metabolomics, bioinformatics, and molecular docking. Cardioprotective effects and mechanisms of ST and active compounds were verified by echocardiography, HE and Masson staining, biochemical analysis, and ELISA in the isoproterenol hydrochloride-induced myocardial ischemia (MI) mice model. The biolabel research suggested that the therapeutic potential of ST for MI may be particularly significant among the heart diseases it may treat. In the isoprenaline hydrochloride-induced MI mice model, ST and its five active compounds (caffeic acid, gallic acid, betulinic acid, esculetin, and cinnamic acid) showed significant protective effects against echocardiographic changes and histopathological damages of the ischemic myocardial tissue. Meanwhile, they showed a tendency to correct mitochondrial structure and function damage and the abnormal expression of 12 biolables (DCTN1, DCTN3, and SCARB2, etc.) in the vesicle-mediated transport pathway, inflammatory cytokines (IL-1ß, IL-6, and IL-10, etc.), and low density lipoprotein receptor (LDLR). The biolabel research identifies a new application value of ST in the treatment of heart diseases. ST and its active compounds inhibit mitochondrial impairments, inflammation, and LDLR deficiency through regulating the vesicle-mediated transport pathway, thus achieving the purpose of treating MI.

Antimicrobial activities of lavandulylated flavonoids in Sophora flavences against methicillin-resistant Staphylococcus aureus via membrane disruption.

INTRODUCTION: The continuous emergence and rapid spread of multidrug-resistant bacteria have accelerated the demand for the discovery of alternative antibiotics. Natural plants contain a variety of antibacterial components, which is an important source for the discovery of antimicrobial agents. OBJECTIVE: To explore the antimicrobial activities and related mechanisms of two lavandulylated flavonoids, sophoraflavanone G and kurarinone in Sophora flavescens against methicillin-resistant Staphylococcus aureus. METHODS: The effects of sophoraflavanone G and kurarinone on methicillin-resistant Staphylococcus aureus were comprehensively investigated by a combination of proteomics and metabolomics studies. Bacterial morphology was observed by scanning electron microscopy. Membrane fluidity, membrane potential, and membrane integrity were determined using the fluorescent probes Laurdan, DiSC3(5), and propidium iodide, respectively. Adenosine triphosphate and reactive oxygen species levels were determined using the adenosine triphosphate kit and reactive oxygen species kit, respectively. The affinity activity of sophoraflavanone G to the cell membrane was determined by isothermal titration calorimetry assays. RESULTS: Sophoraflavanone G and kurarinone showed significant antibacterial activity and anti-multidrug resistance properties. Mechanistic studies mainly showed that they could target the bacterial membrane and cause the destruction of the membrane integrity and biosynthesis. They could inhibit cell wall synthesis, induce hydrolysis and prevent bacteria from synthesizing biofilms. In addition, they can interfere with the energy metabolism of methicillin-resistant Staphylococcus aureus and disrupt the normal physiological activities of the bacteria. In vivo studies have shown that they can significantly improve wound infection and promote wound healing. CONCLUSION: Kurarinone and sophoraflavanone G showed promising antimicrobial properties against methicillin-resistant Staphylococcus aureus, suggesting that they may be potential candidates for the development of new antibiotic agents against multidrug-resistant bacteria.