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.

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.

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).

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.

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.

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.

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.

Matrine and Oxymatrine: evaluating the gene mutation potential using in silico tools and the bacterial reverse mutation assay (Ames test).

The quinolizidine alkaloids matrine and its N-oxide oxymatrine occur in plants of the genus Sophora. Recently, matrine was sporadically detected in liquorice products. Morphological similarity of the liquorice plant Glycyrrhiza glabra with Sophora species and resulting confusion during harvesting may explain this contamination, but use of matrine as pesticide has also been reported. The detection of matrine in liquorice products raised concern as some studies suggested a genotoxic activity of matrine and oxymatrine. However, these studies are fraught with uncertainties, putting the reliability and robustness into question. Another issue was that Sophora root extracts were usually tested instead of pure matrine and oxymatrine. The aim of this work was therefore to determine whether matrine and oxymatrine have potential for causing gene mutations. In a first step and to support a weight-of-evidence analysis, in silico predictions were performed to improve the database using expert and statistical systems by VEGA, Leadscope (Instem®), and Nexus (Lhasa Limited). Unfortunately, the confidence levels of the predictions were insufficient to either identify or exclude a mutagenic potential. Thus, in order to obtain reliable results, the bacterial reverse mutation assay (Ames test) was carried out in accordance with OECD Test Guideline 471. The test set included the plate incorporation and the preincubation assay. It was performed with five different bacterial strains in the presence or absence of metabolic activation. Neither matrine nor oxymatrine induced a significant increase in the number of revertants under any of the selected experimental conditions. Overall, it can be concluded that matrine and oxymatrine are unlikely to have a gene mutation potential. Any positive findings with Sophora extracts in the Ames test may be related to other components. Notably, the results also indicated a need to extend the application domain of respective (Q)SAR tools to secondary plant metabolites.

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.

Undescribed matrine-type alkaloids from Sophora alopecuroides with anti-inflammatory activity.

A phytochemical investigation on the alkaloid fractions of Sophora alopecuroides L. led to the production of 11 undescribed matrine-type alkaloids, sophaloseedlines I-S (1-11), 12 known analogs (12-23), and an unexpected artificial matrine-derived Al(III) complex (24). The corresponding structures were elucidated by the interpretation of spectroscopic analyses, quantum chemical calculation, and six instances (1-4, 18, and 24), verified by X-ray crystallography. The biological activities screening demonstrated that none of the isolates exhibited cytotoxicity against four human cancer cell lines (HepG2, A549, THP-1, and MCF-7) and respiratory syncytial virus (RSV) at 50 µM, while moderate anti-inflammatory activity with IC50 value from 15.6 to 47.8 µM was observed. The key structure-activity relationships of those matrine-type alkaloids for anti-inflammatory effects have been summarized. In addition, the most potent 7-epi-sophoramine (19) and aluminum sophaloseedline T (24) could effectively inhibit the release of pro-inflammatory factors (TNF-α, IL-6, and IL-1ß), as well as the expression of iNOS and COX-2 proteins.

Sophora tonkinensis: response and adaptation of physiological characteristics, functional traits, and secondary metabolites to drought stress.

The medicinal plant Sophora tonkinensis is a characteristic Chinese shrub of karst areas. The arid climate in karst areas produces high-quality S. tonkinensis; however, the mechanisms of drought tolerance are not clear, which restricts sustainable plantings of S. tonkinensis. This study involved a 20-day drought stress experiment with potted S. tonkinensis and threee soil water regimes: control (CK), mild drought (MDT), and severe drought (SDT). Plant morphology, biomass, physiological indicators, alkaloid content, and other changes under drought stress were monitored. The content of soluble sugars and proteins, and activity of antioxidant enzymes in leaves and roots were higher under drought than CK, indicating that S. tonkinensis is tolerant to osmotic stress in early drought stages. Content of matrine and oxymatrine increased gradually with increasing drought duration in the short term. The epidermis of S. tonkinensis leaves have characteristics of desert plants, including upper epidermal waxy layer, lower epidermal villi, and relatively sunken stomata, suggesting that S. tonkinensis has strong drought tolerance. In conclusion, drought stress changed the cell structure of S. tonkinensis, induced antioxidant enzyme activity and increased its resistance to drought.

Six undescribed lavandulylated flavonoids with PTP1B inhibition from the roots of Sophora flavescens.

Six undescribed lavandulylated flavonoids (1-6) were isolated from the roots of Sophora flavescens. Remarkably, compounds 1 and 2, which were composed of a flavane unit and a phloroglucinol unit, were the first reported dimers. Compounds 3 and 4 were the first reported neoflavonoids with lavandulyl units. Compounds 5 and 6 were chalcone with oxidized lavandulyl units. Their structures were fully characterized by cumulative analyses of UV, IR, HRESIMS, NMR and ECD spectroscopic data, along with computational calculations through density functional theory. Compounds 1 and 2 showed significant protein tyrosine phosphatase-1B inhibitory activities with IC50 values of 2.669 and 3.596 µM, respectively.

Alkaloids from the roots of Sophora flavescens and their anti-tumor activity.

Sophora flavescens belongs to Sophora genus of Leguminosae. Its roots are used as a traditional Chinese medicine. In our study on Sophora flavescens roots, 3 new and 19 known alkaloids have been found, including 8 aloperine-type and 14 matrine-type alkaloids. The planar configurations of these compounds were determined by the spectral data, and the absolute configurations of new compounds 1, 2 and 4 were determined by pyridine solvent effect, ECD and snatzke methods, respectively. All compounds were tested for their inhibitory activity on MCF-7 cell growth, and compound 12 exhibited certain inhibitory effects on the growth of MCF-7 cells after 24 h of treatment at a concentration of 20 µM, with inhibition rates of 31.28%. Through target screening and molecular docking, human Rho GTPase activating protein 5 variant and human arachidonate 12-lipoxygenase (12S-type) might be important targets for compound 12 to exert anti-tumor activity.

Sophora genomes provide insight into the evolution of alkaloid metabolites along with small-scale gene duplication.

The genus Sophora (Fabaceae) includes medicinal plants that have been used in East Asian countries since antiquity. Sophora flavescens is a perennial herb indigenous to China, India, Japan, Korea, and Russia. Its dried roots have antioxidant, anti-inflammatory, antibacterial, apoptosis-modulating, and antitumor efficacy. The congeneric S. koreensis is endemic to Korea and its genome is less than half the size of that of S. flavescens. Nevertheless, this discrepancy can be used to assemble and validate the S. flavescens genome. A comparative genomic study of the two genomes can disclose the recent evolutionary divergence of the polymorphic phenotypic profiles of these species. Here, we used the PacBio sequencing platform to sequence and assemble the S. koreensis and S. flavescens genomes. We inferred that it was mainly small-scale duplication that occurred in S. flavescens. A KEGG analysis revealed pathways that might regulate the pharmacologically important secondary metabolites in S. flavescens and S. koreensis. The genome assemblies of Sophora spp. could be used in comparative genomics and data mining for various plant natural products.

Study on the material basis and action mechanisms of sophora davidii (Franch.) skeels flower extract in the treatment of non-small cell lung cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora davidii (Franch.) Skeels Flower (SDF) is a characteristic folk medicine in Yunnan and Guizhou, which can be used to prevent the occurrence of tumors. The extract of SDF (SDFE) is confirmed to be antitumor by pre-experiment. However, effective components and anticancer mechanisms of SDFE are still unclear. AIM OF THE STUDY: The purpose of this study was to explore the material basis and action mechanisms of SDFE in the treatment of non-small cell carcinoma (NSCLC). MATERIALS AND METHODS: UHPLC-Q-Exactive-Orbitrap-MS/MS was used to identify the chemical components of SDFE. The network pharmacology was applied to screen out the main active components, core genes and related signaling pathways of SDFE in treatment of NSCLC. Molecular docking was used to predict the affinity of major components and core targets. The database was applied to predict the mRNA and protein expression levels of core targets in NSCLC. Finally, the experiments in vitro were performed by CCK-8, flow cytometry and western blot (WB). RESULTS: In this study, 98 chemical components were identified by UHPLC-Q-Exactive- Orbitrap-MS/MS. 5 main active components (namely quercetin, genistein, luteolin, kaempferol, isorhamnetin), 10 core genes (namely TP53, AKT1, STAT3, SRC, MAPK3, EGFR, JUN, EP300, TNF, PIK3R1) and 20 pathways were screened out through network pharmacology. The 5 active ingredients were molecularly docked with the core genes, and most the LibDockScore values were higher than 100. The data collected from the database indicated that TP53, AKT1 and PIK3R1 were closely related to the occurrence of NSCLC. The results of experiment in vitro showed that SDFE promoted NSCLC cells apoptosis by down-regulating the phosphorylation of PI3K, AKT and MDM2, up-regulating the phosphorylation of P53, inhibiting the expression of Bcl-2 and up-regulating the expression of Bax. CONCLUSION: The combination of network pharmacology, molecular docking, database validation, and in vitro experimental validation effectively demonstrates that SDFE can promote cell apoptosis by regulating PI3K-AKT/MDM2-P53 signaling pathway, so as to treat NSCLC.

Sophflarine A, a novel matrine-derived alkaloid from Sophora flavescens with therapeutic potential for non-small cell lung cancer through ROS-mediated pyroptosis and autophagy.

BACKGROUND: Novel compounds and more efficient treatment options are urgently needed for the treatment of non-small cell lung cancer (NSCLC). The decoction of Sophora flavescens has been used to treat NSCLC in the clinic, and matrine-type alkaloids are generally considered to be the key pharmacodynamic material basis. But the previous study showed that common matrine-type alkaloids exhibit significant cytotoxicity only when at concentrations close to the millimolar (mM) level. The key antitumor alkaloids in S. flavescens seem to have not yet been revealed. PURPOSE: The aim of this study was to screen water-soluble matrine alkaloid with novel skeleton and enhanced activity from S. flavescens, and to reveal the pharmacological mechanism of its therapeutic effect on NSCLC. METHODS: Alkaloid was obtained from S. flavescens by chromatographic separation methods. The structure of alkaloid was determined by spectroscopic methods, and single-crystal X-ray diffraction. The mechanism of anti-NSCLC in vitro with cellular models was evaluated by MTT assay, western blotting, cell migration and invasion assay, plate colony-formation assay, tube formation assay, immunohistochemistry assay, hematoxylin and eosin staining. The antitumor efficacy in vivo was test in NSCLC xenograft models. RESULTS: A novel water-soluble matrine-derived alkaloid incorporating 6/8/6/6 tetracyclic ring system, named sophflarine A (SFA), was isolated from the roots of S. flavescens. SFA had significantly enhanced cytotoxicity compared with the common matrine-type alkaloids, having an IC50 value of 11.3 µM in A549 and 11.5 µM in H820 cells at 48 h. Mechanistically, SFA promoted NSCLC cell death by inducing pyroptosis via activating the NLRP3/caspase-1/GSDMD signaling pathway, and inhibited cancer cell proliferation by increasing the ROS production to activate autophagy via blocking the PI3K/AKT/mTOR signaling pathway. Additionally, SFA also inhibited NSCLC cell migration and invasion by suppressing EMT pathway, and inhibited cancer cell colony formation and human umbilical vein endothelial cell angiogenesis. In concordance with the above results, SFA treatment blocked tumor growth in an A549 cell-bearing orthotopic mouse model. CONCLUSION: This study revealed a potential therapeutic mechanism of a novel matrine-derived alkaloid, which not only described a rational explanation for the clinical utilization of S. flavescens, but also provided a potential candidate compound for NSCLC treatment.

Phosphorylated bush sophora root polysaccharides protect the liver in duck viral hepatitis by preserving mitochondrial function.

In order to ascertain the mechanism underlying the therapeutic efficacy of Bush sophora root polysaccharides (BSRPS) and phosphorylated Bush sophora root polysaccharides (pBSRPS) in the treatment of in duck viral hepatitis (DVH), an investigation was conducted to assess the protective impact of BSRPS and pBSRPS against duck hepatitis A virus type 1 (DHAV-1) induced mitochondrial dysfunction both in vivo and vitro. The BSRPS underwent modification through the utilization of the sodium trimetaphosphate - sodium tripolyphosphate method, and was subsequently characterized though Fourier infrared spectroscopy and scanning electron microscopy. Following this, the degree of mitochondrial oxidative damage and dysfunction was described through the use of fluorescence probes and various antioxidative enzyme assay kits. Furthermore, the utilization of transmission electron microscopy facilitated the observation of alterations in the mitochondrial ultrastructure within the liver tissue. Our findings demonstrated that both BSRPS and pBSRPS effectively mitigated mitochondrial oxidative stress and conserved mitochondrial functionality, as evidenced by heightened antioxidant enzyme activity, augmented ATP production, and stabilized mitochondrial membrane potential. Meanwhile, the histological and biochemical examinations revealed that the administration of BSRPS and pBSRPS resulted in a reduction of focal necrosis and infiltration of inflammatory cells, thereby mitigating liver injury. Additionally, both BSRPS and pBSRPS exhibited the ability to maintain liver mitochondrial membrane integrity and enhance the survival rate of ducklings infected with DHAV-1. Notably, pBSRPS demonstrated superior performance in all aspects of mitochondrial function compared to BSRPS. The findings indicated that maintaining mitochondrial homeostasis is a crucial factor in DHAV-1 infections, and the administration of BSRPS and pBSRPS may mitigate mitochondrial dysfunction and safeguard liver function.