Transcriptome-wide identification of ARF gene family in medicinal plant Polygonatum kingianum and expression analysis of PkARF members in different tissues.

BACKGROUND: Polygonatum kingianum holds significant importance in Traditional Chinese Medicine due to its medicinal properties, characterized by its diverse chemical constituents including polysaccharides, terpenoids, flavonoids, phenols, and phenylpropanoids. The Auxin Response Factor (ARF) is a pivotal transcription factor known for its regulatory role in both primary and secondary metabolite synthesis. However, our understanding of the ARF gene family in P. kingianum remains limited. METHODS AND RESULTS: We employed RNA-Seq to sequence three distinct tissues (leaf, root, and stem) of P. kingianum. The analysis revealed a total of 31,558 differentially expressed genes (DEGs), with 43 species of transcription factors annotated among them. Analyses via gene ontology and the Kyoto Encyclopedia of Genes and Genomes demonstrated that these DEGs were predominantly enriched in metabolic pathways and secondary metabolite biosynthesis. The proposed temporal expression analysis categorized the DEGs into nine clusters, suggesting the same expression trends that may be coordinated in multiple biological processes across the three tissues. Additionally, we conducted screening and expression pattern analysis of the ARF gene family, identifying 12 significantly expressed PkARF genes in P. kingianum roots. This discovery lays the groundwork for investigations into the role of PkARF genes in root growth, development, and secondary metabolism regulation. CONCLUSION: The obtained data and insights serve as a focal point for further research studies, centred on genetic manipulation of growth and secondary metabolism in P. kingianum. Furthermore, these findings contribute to the understanding of functional genomics in P. kingianum, offering valuable genetic resources.

Structural Characterization of Polygonatum Cyrtonema Polysaccharide and Its Immunomodulatory Effects on Macrophages.

A neutral Polygonatum cyrtonema polysaccharide (NPCP) was isolated and purified from Polygonatum cyrtonema by various chromatographic techniques, including DEAE-52 and Sephadex-G100 chromatography. The structure of NPCP was characterized by HPLC, HPGPC, GC-MS, FT-IR, NMR, and SEM. Results showed that NPCP is composed of glucose (55.4%) and galactose (44.6%) with a molecular weight of 3.2 kDa, and the sugar chain of NPCP was →1)-α-D-Glc-(4→1)-ß-D-Gal-(3→. In vitro bioactivity experiments demonstrated that NPCP significantly enhanced macrophages proliferation and phagocytosis while inhibiting the M1 polarization induced by LPS as well as the M2 polarization induced by IL-4 and IL-13 in macrophages. Additionally, NPCP suppressed the secretion of IL-6 and TNF-α in both M1 and M2 cells but promoted the secretion of IL-10. These results suggest that NPCP could serve as an immunomodulatory agent with potential applications in anti-inflammatory therapy.

Interpreting the Mechanism of Active Ingredients in Polygonati Rhizoma in Treating Depression by Combining Systemic Pharmacology and In Vitro Experiments.

Polygonati Rhizoma (PR) has certain neuroprotective effects as a homology of medicine and food. In this study, systematic pharmacology, molecular docking, and in vitro experiments were integrated to verify the antidepressant active ingredients in PR and their mechanisms. A total of seven compounds in PR were found to be associated with 45 targets of depression. Preliminarily, DFV docking with cyclooxygenase 2 (COX2) showed good affinity. In vitro, DFV inhibited lipopolysaccharide (LPS)-induced inflammation of BV-2 cells, reversed amoeba-like morphological changes, and increased mitochondrial membrane potential. DFV reversed the malondialdehyde (MDA) overexpression and superoxide dismutase (SOD) expression inhibition in LPS-induced BV-2 cells and decreased interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and IL-6 mRNA expression levels in a dose-dependent manner. DFV inhibited both mRNA and protein expression levels of COX2 induced by LPS, and the activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) and caspase1 was suppressed, thus exerting an antidepressant effect. This study proves that DFV may be an important component basis for PR to play an antidepressant role.

Metabolomics and HS-SPME-GC-MS-based analysis of quality succession patterns and flavor characteristics changes during the fermentation of Lycium barbarum and Polygonatum cyrtonema compound wine.

This work set out to investigate how the physicochemical markers, volatiles, and metabolomic characteristics of mixed fermented the fermentation of Lycium barbarum and Polygonatum cyrtonema compound wine (LPCW) from S. cerevisine RW and D. hansenii AS2.45 changed over the course of fermentation. HS-SPME-GC-MS combined with non-targeted metabolomics was used to follow up and monitor the fermentation process of LPCW. In total, 43 volatile chemical substances, mostly alcohols, esters, acids, carbonyl compounds, etc., were discovered in LPCW. After 30 days of fermentation, phenylethyl alcohol had increased to 3045.83 g/mL, giving off a rose-like fresh scent. The biosynthesis of valine, leucine, and isoleucine as well as the metabolism of alanine, aspartic acid, and glutamic acid were the major routes that led to the identification of 1385 non-volatile components in total. This study offers a theoretical foundation for industrial development and advances our knowledge of the fundamental mechanism underlying flavor generation during LPCW fermentation.

Identification Markers Responsible for Differentially Processed Polygonatum cyrtonema Hua by Ultra-Performance Liquid Chromatography with Quadruple-Time-of-Flight Mass Spectrometry.

The rhizome of Polygonatum cyrtonema Hua has been used as a traditional Chinese medicine for over 2000 years. The fresh Chinese herb possesses micro toxicity and is thus traditionally alternately steamed and basked nine times to alleviate the toxicity and enhance the pharmaceutical efficacy. Different processing cycles usually result in variable therapeutic effects in the processed Polygonatum cyrtonema Hua (P-PCH). However, it can be hard to tell these various P-PCHs apart at present. To identify the P-PCHs that had undergone repeated steaming one to nine times, the chemical constituents were profiled based on Ultra-Performance Liquid Chromatography with Quadruple-Time-of-Flight Mass Spectrometry, and the Principal Component Analysis and Cluster Analysis methods were adopted to discriminate different cycles of P-PCH. A total of 44 characteristic markers were identified, which allowed the P-PCHs to be discriminated exactly.

Polysaccharides from Polygonatum kingianum Collett & Hemsl ameliorated fatigue by regulating NRF2/HO-1/NQO1 and AMPK/PGC-1α/TFAM signaling pathways, and gut microbiota.

Polygonatum kingianum Coll & Hemsl is an important Chinese medicine used for enhancing physical function and anti-fatigue, and polysaccharides (PKPs) are considered as the main bioactive components. However, the mechanisms through which PKPs exert their anti-fatigue effects are not fully understood. This study aimed more comprehensively to explore the anti-fatigue mechanisms of PKPs, focusing on metabolism, protein expression, and gut flora, by using exhaustive swimming experiments in mice. Results showed a significant increase in the exhaustive swimming time of the mice treated with PKPs, especially in the high-dose group (200 mg/kg/day). Further studies showed that PKPs remarkably improves several fatigue-related physiological indices. Additionally, 16S rRNA sequence analysis showed that PKPs increased antioxidant bacteria (e.g., g_norank_f_Muribaculaceae) and the production of short-chain fatty acids (SCFAs), while reducing the abundance of harmful bacteria (e.g., g_Escherichia-Shigella and g_Helicobacter). PKPs also mitigated oxidative stress through activating the NRF2/HO-1 signaling pathway, and promoted energy metabolism by upregulating the expression of AMPK/PGC-1α/TFAM signaling pathway proteins. This research may offer theoretical support for incorporating PKPs as a novel dietary supplement in functional foods targeting anti-fatigue properties.

Enhanced hypoglycemic effects of konjac glucomannan combined with Polygonatum cyrtonema Hua polysaccharide in complete nutritional liquid diet fed type 2 diabetes mice.

In our aging society, dysphagia and malnutrition are growing concerns, necessitating intervention. Liquid nutrition support offers a practical solution for traditional dietary issues, but it raises a key issue: the potential for post-meal glucose spikes impacting efficacy. This study examined the effects of supplementation of Polygonatum cyrtonema Hua polysaccharide (PCP), konjac glucomannan (KGM) and their combination on acute phase postprandial glycemic response and long-term glucose metabolism in T2DM mice on a complete nutritional liquid diet. KGM was more effective in reducing postprandial glucose response, while PCP was more prominent in ameliorating long-term glucose metabolism. The KGM-PCP combination demonstrated superior outcomes in fasting blood glucose, insulin, and glucose homeostasis. PCP and KGM also influenced the composition and abundance of the gut microbiome, with the H-PCP group showing optimal performance. Moreover, the KGM-PCP combination improved body weight, lipid homeostasis, and liver health the most. PCP potentially regulates glycemia through metabolic pathways, while KGM improves glycemic metabolism by reducing postprandial glucose levels in response to viscous intestinal contents. This research identifies the structure, viscosity properties, and hypoglycemic effects of KGM and PCP in complete nutritional liquid diet fed T2DM mice, enabling their strategic utilization as hypoglycemic components in nutritional administration and glycemic regulation.

Anti-Aging in Caenorhabditis elegans of Polysaccharides from Polygonatum cyrtonema Hua.

Polygonatum cyrtonema Hua, the dried rhizome of Polygonum multiflorum from the Liliaceae family, is a widely used medicinal herb with a long history of application. Its main active ingredients are polysaccharides, which have been demonstrated in contemporary studies to effectively delay the aging process. In the present study, homogeneous polysaccharide (PCP-1) was obtained after the purification and isolation of polysaccharides from Polygonatum cyrtonema Hua (PCP). The anti-aging activities of both were compared, and the possible mechanism of action for exerting anti-aging activity was explored using Caenorhabditis elegans (C. elegans). Research has indicated that PCP and PCP-1 exhibit potent anti-oxidant and anti-aging properties. Of particular note is that PCP-1 acts better than PCP. The two were able to prolong the lifespan of nematodes, improve the stress resistance of nematodes, reduce the accumulation of lipofuscin in the intestine, decrease the content of ROS and MDA in the body, increase the activity of the antioxidant enzymes SOD and CAT, promote the nuclear translocation of DAF-16, down-regulate the mRNA levels of the age-1 and daf-2 genes of the IIS pathway in nematodes, and up-regulate the expression of the daf-16, skn-1, sod-3, and hsp-16.2 genes. Based on the aforementioned findings, it is possible that the mechanism by which PCP and PCP-1 exert anti-aging effects may be through negative regulation of the IIS pathway, activation of the transcription factor DAF-16/FOXO, and enhancement of oxidative defenses and stress resistance in nematodes. Overall, the present study illustrated the great potential of polysaccharides from Polygonatum cyrtonema Hua in anti-aging and antioxidant activities. Specifically, PCP-1 demonstrated superior characteristics, which provides a reference for the future development of Polygonatum cyrtonema Hua polysaccharides.

Interaction between lactic acid bacteria and Polygonatum sibiricum saponins and its application to microencapsulated co-delivery.

This study aimed to investigate the interaction between L.casei and L.bulgaricus with Polygonatum sibiricum saponins (PSS) and to explore the co-microencapsulation to reduce their loss rate during storage and consumption. 1% PSS was added to the culture broth, and it was found that the growth and metabolism of the strains were accelerated, especially in the compound probiotic group, indicating that PSS has potential for prebiotics. LC-MS observed significant differences in the composition and content of saponins in PSS. The metabolomics results suggest that the addition of PSS resulted in significant changes in the metabolites of probiotics. In addition, it was found that the combination of probiotics and PSS may have stronger hypoglycemic ability (ɑ-glucosidase, HepG2). Finally, a co-microencapsulated delivery system was constructed using zein and isomaltooligosaccharide. This system can achieve more excellent resistance of probiotics and PSS in gastrointestinal fluids, effectively transporting both to the small intestine.

Modulatory effects of fermented Polygonatum cyrtonema Hua on immune homeostasis and gut integrity in a dextran-sulfate-sodium-induced colitis model.

The gut health-promoting properties of saponin-rich Polygonatum cyrtonema Hua (FP) fermented with Lactobacillus plantarum P9 were explored in a dextran sulfate sodium (DSS)-induced colitis mouse model. FP supplementation effectively inhibited DSS-induced physiological alteration and impaired immune responses by reducing the disease activity index (DAI) score and restoring the T helper (Th) 1/Th2 and regulatory T (Treg)/Th17 ratios. In addition, FP supplementation protected the gut barrier function against DSS-induced damage via upregulation of zonula occludens (ZO)-1 and occludin and downregulation of pro-inflammatory cytokines, including interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), IL-18, and the granulocyte-macrophage colony-stimulating factor (GM-CSF). This study further elucidated the potential mechanisms underlying the FP-mediated suppression of the plasticity of type 3 innate lymphoid cells (ILC3) and subsequent macrophage polarization. Therefore, the FP supplementation effectively restored mucosal immune homeostasis and enhanced gut integrity. In addition, it suppressed the growth of Escherichia-Shigella and Enterococcus and promoted the enrichment of probiotics and short-chain fatty acid-producing microbes, such as Romboutsia, Faecalibaculum, and Blautia. In conclusion, P. cyrtonema Hua fermented with L. plantarum P9 might be a promising dietary intervention to improve gut health by sustaining overall gut homeostasis and related gut integrity.

Accumulation mechanism of metabolite markers identified by machine learning between Qingyuan and Xiushui counties in Polygonatum cyrtonema Hua.

Polygonatum cyrtonema Hua is a traditional Chinese medicinal plant acclaimed for its therapeutic potential in diabetes and various chronic diseases. Its rhizomes are the main functional parts rich in secondary metabolites, such as flavonoids and saponins. But their quality varies by region, posing challenges for industrial and medicinal application of P. cyrtonema. In this study, 482 metabolites were identified in P. cyrtonema rhizome from Qingyuan and Xiushui counties. Cluster analysis showed that samples between these two regions had distinct secondary metabolite profiles. Machine learning methods, specifically support vector machine-recursive feature elimination and random forest, were utilized to further identify metabolite markers including flavonoids, phenolic acids, and lignans. Comparative transcriptomics and weighted gene co-expression analysis were performed to uncover potential candidate genes including CHI, UGT1, and PcOMT10/11/12/13 associated with these compounds. Functional assays using tobacco transient expression system revealed that PcOMT10/11/12/13 indeed impacted metabolic fluxes of the phenylpropanoid pathway and phenylpropanoid-related metabolites such as chrysoeriol-6,8-di-C-glucoside, syringaresinol-4'-O-glucopyranosid, and 1-O-Sinapoyl-D-glucose. These findings identified metabolite markers between these two regions and provided valuable genetic insights for engineering the biosynthesis of these compounds.

Network pharmacology analysis, molecular docking integrated experimental verification reveal ß-sitosterol as the active anti-NSCLC ingredient of Polygonatum cyrtonema Hua by suppression of PI3K/Akt/HIF-1α signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonatum cyrtonema Hua (Huangjing) is a Chinese herb that is considered by ancient Chinese healers to have the effect of nourishing yin and moisturizing the lungs. It is clinically used to treat diseases of the pulmonary system, including non-small cell lung cancer. However, the precise active components and underlying mechanisms of Huangjing in the context of treating NSCLC remain uncertain. AIM OF THE STUDY: This study aimed to explore the active components and mechanisms of Huangjing for the treatment of NSCLC by means of data mining, network pharmacology, and in vitro and vivo experiments. MATERIALS AND METHODS: First, the main active compounds and key targets of Huangjing were predicted by network pharmacology. The potential key targets of Huangjing were molecularly docked with the main active compounds using Pymol. In vivo, we verified whether Huangjing and its main active compound have anti-lung cancer effects. Key targets were verified by PCR and immunohistochemistry. In vitro, we verified the effects of Huangjing's main active compound on the proliferation, apoptosis, and migration of A549 cells by CCK-8, colony formation, wound healing assay, and flow cytometry. Key targets and signaling pathway were validated by PCR and Western blot. RESULTS: The network pharmacology results suggested that ß-sitosterol was the main active substance. TP53, JUN, AKT1, MAPK14, ESR1, RELA, HIF1A, and RXRA were potential targets of Huangjing. Molecular docking results suggested that MAPK14, HIF-1α, and RXRA docked well with ß-sitosterol. In vivo tests also confirmed that Huangjing could significantly inhibit the growth of lung cancer tumors, while PCR and immunohistochemistry results suggested that the expression of HIF-1α was significantly decreased. Critically, KEGG analysis indicated that the PI3K/Akt/HIF-1α signaling pathway was recommended as one of the main pathways related to the anti-NSCLC effect of Huangjing. We conducted in vitro experiments to confirm the significant impact of ß-sitosterol on the proliferation, apoptosis, migration, and colony formation of A549 cells. Furthermore, our findings indicate that a high dosage of ß-sitosterol may effectively decrease the expression of HIF-1α, AKT1, JUN and RELA in A549 cells. Similarly, in vitro experiments also revealed that high doses of ß-sitosterol could inhibit the PI3K/Akt/HIF-1α signaling pathway. CONCLUSIONS: We discovered Huangjing and its main active ingredient, ß-sitosterol, can reduce HIF-1α, AKT1, JUN and RELA expression and decrease non-small cell lung cancer growth through the PI3K/Akt/HIF-1α signaling pathway.

Research progress on medicinal components and pharmacological activities of polygonatum sibiricum.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonatum sibiricum, commonly known as Siberian Solomon's seal, is a traditional herb widely used in various traditional medical systems, especially in East Asia. In ancient China, the use of polygonatum sibiricum in medicine and food was mentioned in Li Shizhen's Bencao Gangmu of traditional Chinese medicine (TCM). It was also used in history of India in Vedic medicine. The plant is rich in bioactive substances such as polysaccharides, saponins, flavonoid and alkaloids. AIM OF THE REVIEW: The aim of this review is to understand the pharmacological and pharmacokinetics research progress of the major components of polygonatum sibiricum, and to prospect its potential application and development in the treatment of various diseases. MATERIALS AND METHODS: We conducted a systematic literature search against major online databases on the Web, including PubMed, ancient books, patents, PubMed, Wiley, Google Scholar, Web of Science, and others. We select the pharmacological process and mechanism of the main components of polygonatum sibiricum in a variety of diseases, and make a strict but careful supplement and in-depth elaboration to this review. RESULTS: Several studies have demonstrated the strong antioxidant properties of polygonatum extract, which can be attributed to the presence of flavonoids and other polyphenol compounds; for diabetes and other metabolic-related diseases, polygonatum saponins have particular advantages in regulating intestinal flora and lipoprotein concentration in organisms. In addition, the polysaccharides extracted from this plant have a strong anti-inflammatory effect, which is related to its ability to regulate proinflammatory cytokine and mediators. In the aspect of anti-tumor effect, polygonatum derivatives can induce cancer cell apoptosis mainly by adjusting the cell membrane potential and cell cycle. It is worth noting that the combined action of the main components of polygonatum also offers promising solutions for the treatment of the disease. CONCLUSION: Polygonatum polysaccharide has therapeutic effects on many diseases by adjusting cell signal pathways, polygonatum sibiricum have significant advantages in regulating intestinal flora, inducing apoptosis of tumor cells, activating antioxidant processes, etc. Further research and basic exploration are needed to prove the function and mechanisms of the main components of polygonatum sibiricum on related diseases. The study on the immunomodulatory properties of polygonatum revealed its potentiality of enhancing immune function, which made it an interesting subject for further exploration in the field of immunotherapy.

Isolation, Purification, Fractionation, and Hepatoprotective Activity of Polygonatum Polysaccharides.

In this study, three homogeneous fractions, PSP-N-b-1, PSP-N-b-2, and PSP-N-c-1, were obtained from an aqueous extract of Polygonatum using DEAE cellulose column chromatography, CL-6B agarose gel chromatography, and Sephadex G100 chromatography. Their monosaccharide compositions and molecular weights were analyzed. The results revealed that PSP-N-b-1, PSP-N-b-2, and PSP-N-c-1 are primarily composed of six monosaccharides: Man (mannose), GlcA (glucuronic acid), Rha (rhamnose), GalA (galacturonic acid), Glc (glucose), and Ara (arabinose), with molecular weights of 6.3 KDa, 5.78 KDa, and 3.45 KDa, respectively. Furthermore, we observed that Polygonatum polysaccharides exhibited protective effects against CCL4-induced liver damage in HepG2 cells in vitro, operating through both anti-oxidant and anti-inflammatory mechanisms. Our research findings suggest that Polygonatum polysaccharides may emerge as a promising option in the development of hepatoprotective drugs or functional foods with anti-inflammatory and antioxidant properties.

Effect of Polygonatum sibiricum saponins on gut microbiota of mice with ulcerative colitis.

Polygonatum sibiricum is a plant with medicinal and nutritional properties. Saponins are the important biologically active components of Polygonatum sibiricum. In this study, the specific components of Polygonatum sibiricum saponins (PSS) were analyzed, and the regulation effect of PSS on intestinal flora in patients with ulcerative colitis (UC) was investigated by inducing male Kunming mice with dextran sulfate sodium (DSS). PSS could ameliorate the symptoms of weight loss, high DAI score and colon length reduction compared to DSS-induced treatment. Colonic fragments were taken for H&E staining and histopathological scoring. PSS could significantly improve the pathological abnormality of colitis mice. 16S rRNA analysis showed that the intestinal microbial community of mice treated with DSS was significantly damaged. PSS could restore the richness and diversity of intestinal microbial flora, reduce the number of pathogenic bacteria, and increase the abundance of Lactobacillus spp. and Muribaculaceae, and improve the intestinal microbial flora disorder. Generally, PSS had an obvious effect in relieving colitis in mice. This study confirmed that Polygonatum sibiricum saponins play a therapeutic and palliative role in ulcerative colitis by regulating the microbiome balance.

Isolation, purification, and physicochemical characterization of Polygonatum polysaccharide and its protective effect against CCl4-induced liver injury via Nrf2 and NF-κB signaling pathways.

This study aimed to provide scientific evidence that Polygonatum polysaccharide can be developed as a dietary supplement and medication for treating liver injuries. A water-soluble polysaccharide (PSP-N-c-1), with an average molecular weight of 3.45 kDa, was isolated and purified from the water extract of Polygonatum using DEAE cellulose column chromatography, CL-6B agarose gel chromatography, and Sephadex G100 chromatography. High-performance liquid chromatography, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectroscopy analyses revealed that PSP-N-c-1 might be linear α-(1 â†’ 4)-glucans with α-Glcp residues linked to the backbone at C-6. In vitro experiments revealed that PSP-N-c-1 exhibited protective effects against CCl4-induced damage in HepG2 cells. In vivo experiments demonstrated that PSP-N-c-1 exhibited a hepatoprotective effect by enhancing antioxidant enzyme activity, inhibiting lipid peroxidation, and reducing the activity of pro-inflammatory mediators. Besides, PSP-N-c-1 could attenuate oxidative stress and inflammatory responses by activating the Nrf2-mediated signaling pathways and regulating the TLR4-mediated NF-κB signaling pathways. These findings demonstrated that PSP-N-c-1 may serve as a supplement for alleviating chemical liver damage.

Investigation of natural deep eutectic solvent for the extraction of crude polysaccharide from Polygonatum kingianum and influence of metal elements on its immunomodulatory effects.

In this study, natural deep eutectic solvent (NADES) was used to extract Polygonatum kingianum crude polysaccharide (PKCP) and response surface methodology (RSM) was designed to optimize the extraction procedure. The immunomodulatory effect of PKCP and the influence of metal elements on its immunomodulatory effect were further discussed. The optimum conditions for PKCP extraction were obtained by RSM optimization: NADES were synthesized with a 1:2 choline chloride-glycerol molar ratio, then extracted at a liquid-solid ratio of 16.6 mL g-1 and water content of 31.2 % for 60 min at 60 °C. This method was used for the extraction of PKCP, and the extraction efficiency was 29.69 %, which was 2.5 times greater than the conventional method of water extraction. In the concentration range of 200-800 µg mL-1, PKCP could activate macrophages, promoting NO secretion and mRNA expression of interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) in a dose-dependent way. NO secretion and cytokine expression were not affected when the metal elements were spiked to the equivalent of the metal elements contained in Polygonatum kingianum. When the content of metal elements was higher, the secretion of NO and the gene expression of iNOS were both decreased, which may affect the immunomodulatory effect of Polygonatum kingianum.

Combination of Polygonatum Rhizoma and Scutellaria baicalensis triggers apoptosis through downregulation of PON3-induced mitochondrial damage and endoplasmic reticulum stress in A549 cells.

OBJECTIVE: Scutellaria baicalensis (SB) and Polygonatum Rhizoma (PR), two traditional Chinese medicines, are both known to suppress cancer. However, the mechanism and effect of combined treatment of them for lung cancer are rarely known. Investigating the combined effect of SB and PR (hereafter referred to as SP) in potential mechanism of lung cancer is required. This study was to evaluate the inhibitory effects of SP on A549 cell growth and to explore the underlying molecular mechanisms. METHODS: According to the theory of Chinese medicine and network pharmacology, in the in vivo experiment, a mouse model of carcinoma in situ was constructed, and lung carcinoma in situ tissues were collected for proteomics analysis, hematoxylin-eosin staining, and CK19 immunohistochemistry. In the in vitro experiment, lung cancer A549 cells at logarithmic growth stage were taken, and the inhibitory effect of SP on the proliferation of A549 cells was detected by CCK8 method. The expression of PON3 was detected by quantitative polymerase chain reaction and western blot. In addition, the effect of SP on the induction of apoptosis in A549 cells and the changes of membrane potential and reactive oxygen species (ROS) content were detected by flow cytometry. The changes of PON3 content in endoplasmic reticulum (ER) are observed by laser confocal microscopy, whereas the effects of SP on the expression of apoptosis-related proteins and ER stress-related proteins in A549 cells were examined by western blot. RESULT: By searching the Traditional Chinese Medicines of Systems Pharmacology (TCMSP) (https://www.tcmspe.com/index.php) database and SymMap database, the respective target genes of PR and SB were mapped into protein network interactions, and using Venn diagrams to show 38 genes in common between PR and SB and lung cancer, SP was found to play a role in the treatment of lung cancer. In vivo experiments showed that in a lung carcinoma in situ model, lung tumor tissue was significantly lower in the SP group compared with the control group, and PON3 was shown to be downregulated by lung tissue proteomics analysis. The combination of SP was able to inhibit the proliferation of A549 cells in a concentration-dependent manner (p < .0001). The expression levels of apoptosis-related proteins and ER stress proteins were significantly increased and the expression levels of PON3 and anti-apoptosis-related proteins were decreased in A549 cells. At the same time, knockdown of PON3 could inhibit tumor cell proliferation (p < .0001). The combination of different concentrations of SP significantly induced apoptosis in A549 cells (p < .05; p < .0001), increased ROS content (p < .01), and damaged mitochondrial membrane potential of A549 cells (p < .05; p < .0001), and significantly increased the expression levels of apoptosis-related proteins and ER stress proteins in lung cancer A549 cells. CONCLUSION: SP inhibits proliferation of lung cancer A549 cells by downregulating PON3-induced apoptosis in the mitochondrial and ER pathways.

Complete genome sequence of polygonatum kingianum mottle virus infecting Polygonatum kingianum Coll. et Hemsl in Yunnan, China.

The complete genome sequence of a putative novel potyvirus, tentatively named "polygonatum kingianum mottle virus" (PKgMV; GenBank accession no. ON428226), infecting Polygonatum kingianum in China, was obtained by next-generation sequencing (NGS), reverse transcription polymerase chain reaction (RT-PCR), and rapid amplification of cDNA ends (RACE). PKgMV exhibits the typical genome organization and characteristics of members of the genus Potyvirus, with a length of 10,002 nucleotides (nt) and a large open reading frame (nt 108 to 9,746) encoding a polyprotein of 3,212 amino acids (aa) (363.68 kDa). Pairwise comparisons revealed that the PKgMV polyprotein shares 50.5-68.6% nt and 43.1-72.2% aa sequence identity with reported members of the genus Potyvirus. Moreover, phylogenetic analysis indicated that PKgMV is closely related to polygonatum kingianum virus 1 (PKgV1; accession no. MK427056). These results suggest that the PKgMV is a novel member of the genus Potyvirus of the family Potyviridae.

Distinct toxic effects, gene expression profiles, and phytohormone responses of Polygonatum cyrtonema exposed to two different antibiotics.

The excessive usage of veterinary antibiotics has raised significant concerns regarding their environmental hazard and agricultural impact when entering surface water and soil. Animal waste serves as a primary source of organic fertilizer for intensive large-scale agricultural cultivation, including the widely utilized medicinal and edible plant, Polygonatum cyrtonem. In this study, we employed a novel plant stress tissue culture technology to investigate the toxic effects of tetracycline hydrochloride (TCH) and sulfadiazine (SDZ) on P. cyrtonema. TCH and SDZ exhibited varying degrees of influence on plant growth, photosynthesis, and the reactive oxygen species (ROS) scavenging system. Flavonoid levels increased following exposure to TCH and SDZ. The biosynthesis and signaling pathways of the growth hormones auxin and gibberellic acid were suppressed by both antibiotics, while the salicylic acid-mediated plant stress response was specifically induced in the case of SDZ. Overall, the study unveiled both common and unique responses at physiological, biochemical, and molecular levels in P. cyrtonema following exposure to two distinct types of antibiotics, providing a foundational framework for comprehensively elucidating the precise toxic effects of antibiotics and the versatile adaptive mechanisms in plants.