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Stimulation of pituitary-adrenocortical system by ginseng saponin.

Effects of preparations of saponin mixture and isolated ginsenosides, extracted from the root of Panax ginseng, on plasma corticotropin (ACTH) and corticosterone concentrations in rats were determined by the radioimmunoassay and competitive protein binding method. When ginseng saponin mixture was administered to rats intraperitoneally, plasma ACTH and corticosterone increased significantly 30, 60 and 90 min after the treatment. The kinetic pattern of the increase in plasma ACTH was almost parallel to that in plasma corticosterone. Isolated ginsenoside, protopanaxadiol or protopanaxatriol glycoside, also increased plasma corticosterone. The ginseng-induced increase in plasma corticosterone was suppressed by pretreatment with dexamethasone. Thus the ginseng saponin was found to act on the hypothalamus and/or hypophysis primarily, and stimulated ACTH secretion which resulted in increased synthesis of corticosterone in the adrenal cortex.

Adrenocorticotropic Hormone

Genome analysis and antagonistic activity of Streptomyces sp. strain J36 against Phytophthora cactorum.

The Phytophthora blight of Panax notoginseng, caused by Phytophthora cactorum, is a devastating oomycete disease. Biocontrol strategies hold immense potential for inhibiting the spread of P. cactorum. We isolated 72 actinobacteria from soil and screened their antagonistic activity against P. cactorum. Both strain J36 and its cell-free filtrate exhibited strong antagonistic activity against P. cactorum and were therefore selected. Based on the 16S rRNA gene phylogenetic tree, strain J36 formed a well supported subclade with Streptomyces zaomyceticus NRRL B-2038 (bootstrap value 100%). However, because 16S rRNA sequences often lack sufficient resolution for species-level discrimination, we performed multilocus sequence analysis (MLSA) using three housekeeping genes (rpoB, recA, and atpD). The MLSA results consistently placed strain J36 within the same cluster as S. zaomyceticus NRRL B-2038, with a bootstrap support of 99%, indicating a close phylogenetic relationship. To further clarify the taxonomic status, we calculated the average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain J36 and the type strain of S. zaomyceticus NBC-00415T. The ANI value was 90.91% and the dDDH value was 39.30%, both well below the accepted thresholds for species demarcation (ANI&#x202f;<&#x202f;95%, dDDH < 70%). These genomic indices therefore strongly support that strain J36 represents a novel species within the genus Streptomyces. Through whole-genome sequencing and CAZymes analysis, a total of 98 carbohydrate-active enzymes (CAZymes) were detected, including 2 cellulase and 2 &#x3b2;-1,3-glucanases. The cell-free filtrate, which exhibited strong antagonistic activity against P. cactorum, also showed high activities of cellulase and &#x3b2;-1,3-glucanase, suggesting that these enzymes may be involved in its anti-oomycete activity. These findings suggest that J36 has potential as a biocontrol candidate, although further in vivo evaluation is needed to confirm its efficacy against Phytophthora blight of P. notoginseng.

Panax notoginseng

Stimulatory effect of ginsenosides on DNA, protein and lipid synthesis in rat bone marrow and participation of cyclic nucleotides.

Effects of several kinds of ginsenosides, saponins from Panax ginseng on DNA, RNA, protein and lipid synthesis in bone marrow were investigated. Single i.p. injection of 0.5--1 mg/100 g body weight of ginsenosides Rb2, Rc, Re and Rg1 4 h prior to the sacrifice increased DNA synthesis in bone marrow cells. RNA, protein and lipid synthesis were also increased. The direct addition of ginsenosides Rb1, Rb2 and Rc mixture (GNS) enhanced DNA synthesis. Cyclic AMP levels in bone marrow cells were decreased 20 min after i.p. injection of ginsenosides Rb2, Rc and Rg1 and the direct addition of ginsenosides Rb2, Rc and Rg1 also decreased cyclic AMP levels. While cyclic GMP levels were increased by administration of ginsenosides Rb2, Re and Rg1. Relationship between chemical structure and actions of ginsenosides and the role of cyclic nucleotides in the stimulatory action of ginsenosides on DNA synthesis in bone marrow cells were discussed.

Animals

Epigenetic activation of NK-cell effector programs and caspase-8-dependent apoptosis mediates the antitumor activity of LGP in NSCLC.

BACKGROUND: Effective activation of natural killer (NK) cell cytotoxicity and caspase-8-dependent extrinsic apoptosis remains a major challenge in non-small cell lung cancer (NSCLC). Epigenetic mechanisms regulating NK cell function within the tumor microenvironment are poorly understood and rarely targeted therapeutically. METHODS: The antitumor activity of Li-Ginseng Powder (LGP), a specifically processed Panax ginseng formulation enriched in rare ginsenosides (Rh4, Rg3, Rg5, Rk1, and Rk3), was evaluated in human lung cancer A549&#x202f;cells and A549 xenograft mouse models. NK cell infiltration and activation were assessed by flow cytometry, immunoblotting, and immunohistochemistry. Whole-genome bisulfite sequencing (WGBS) was performed to analyze DNA methylation changes. The effects of LGP ginsenosides (LGG) on tumor cell apoptosis and death receptor signaling were examined in vitro. RESULTS: LGP significantly suppressed tumor growth and enhanced systemic and intratumoral NK cell activation. Promoter demethylation of NK cell effector genes, including Ncr1, Gzmb, Nktr, and Itgal, was associated with increased NK cell infiltration and activation, elevated granule-mediated cytotoxicity, and enhanced IFN-&#x3b3; signaling. In parallel, LGP treatment induced caspase-8-dependent apoptosis associated with increased expression of membrane death receptors, their ligands, FADD, and procaspase-8 in tumor tissues. In vitro, LGG upregulated these apoptosis-initiating proteins and triggered caspase-8 activation in A549&#x202f;cells independent of promoter methylation changes. Collectively, these immune-associated and tumor-intrinsic responses contributed to robust tumor suppression with a favorable systemic safety profile. CONCLUSIONS: LGP exerts dual antitumor effects characterized by enhanced NK-cell activation and increased sensitivity of tumor cells to caspase-8-dependent extrinsic apoptosis. These coordinated immune-associated and apoptosis-sensitizing effects underscore the therapeutic potential of LGP for the treatment of NSCLC.

DNA methylation

Dissecting the anti-obesity components of ginseng: How ginseng polysaccharides and ginsenosides target gut microbiota to suppress high-fat diet-induced obesity.

INTRODUCTION: Ginseng demonstrates therapeutic potential in treating obesity, with both experimental and clinical studies suggesting its anti-obesity effects are mediated by gut microbiota. Nonetheless, the specific chemical components responsible for this effect remain largely unidentified. OBJECTIVES: This study aims to investigate the anti-obesity effects and mechanisms of ginseng polysaccharides (GP) and ginsenosides (GS), the primary chemical components of ginseng, with a focus on their impact on gut microbiota. METHODS: The impact of GP and GS on high-fat diet (HFD)-induced obesity was assessed using a mouse model. Molecular mechanisms were explored through a combination of chemical analysis, metagenomics, RT-qPCR, ELISA, and biochemical assays. RESULTS: GP or GS administration effectively prevented adiposity in HFD-fed mice, and both effects were mediated by gut microbiota. Chemical analysis revealed diverse glycosyl groups in GP and GS. Metagenomics data suggested that GP-enriched species, e.g., Bacteroides stercorirosoris and Clostridiales bacterium encoded carbohydrate-active enzymes GH35, GH43 and PL9_1, while GS-enriched Sulfurospirillum halorespirans encoded GH16_5. These enzymes facilitated the utilization of glycosyl groups in GP and GS, selectively stimulating bacterial growth and reshaping the gut microbiota. Furthermore, bacterial species enriched by GP or GS encoded specific functional genes involved in short-chain fatty acid (SCFA) synthesis (K00625 and K00925 for GP; K18118, K00100, and K18122 for GS) and intestinal gluconeogenesis (IGN) (K01678, K00024, and K01596 for GP; K18118 and K00278 for GS). Consequently, the SCFA-GLP-1/PYY signaling and IGN were activated by both GP and GS to ameliorate obesity phenotypes. CONCLUSION: GP and GS, containing diverse glycosyl groups, selectively stimulate specific gut bacteria, triggering mechanisms involved in SCFA-GLP-1/PYY signaling and IGN activation to reduce adiposity in HFD-fed mice. The study enhances understanding of the chemical components crucial for the gut microbiota-mediated anti-obesity effect of ginseng. The mechanistic understanding provides valuable insights for developing ginseng-based drugs or health products to combat obesity.

Gastrointestinal Microbiome

Exploring the mechanism of Shengmai San in treating lung adenocarcinoma based on bioinformatics and molecular dynamics simulation.

To investigate the mechanism of Shengmai San (SMS) in the treatment of lung adenocarcinoma (LUAD) based on an integrated strategy combining "network pharmacology, bioinformatics, molecular docking, and molecular dynamics simulation," aiming to provide a precise combination therapy strategy and identify potential bioactive compounds. Differentially expressed genes in LUAD were identified from the Gene Expression Omnibus database using R (originally developed at Bell Laboratories and currently managed by Lucent Technologies). SMS components (ginseng, Ophiopogon japonicus, and Schisandra chinensis) were retrieved from encyclopaedia of traditional Chinese medicine, with Lipinski-compliant compounds selected. Compound targets were predicted via SwissTargetPrediction and Similarity Ensemble Approach. Intersecting targets between differentially expressed genes and compound targets were identified for "herbs-compounds-targets-disease" network construction. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed. Hub targets were identified by analyzing the protein-protein interaction network. High-prognostic relevance targets were screened from The Cancer Genome Atlas. Compounds targeting these were identified through the herbs-compounds-targets-disease network, and absorption, distribution, metabolism, excretion, and toxicity-compliant compounds were selected using SwissADME (a web-based tool provided by the Molecular Modeling Group of the Swiss Institute of Bioinformatics). Core regulatory targets were identified through molecular docking, with complex stability assessed by molecular dynamics simulations. The key bioactive compounds of SMS for treating LUAD were identified as 7-hydroxy-2,5-dimethyl-4H-1-benzopyran-4-one, N-trans-feruloyltyramine, paprazine, and (E)-N-[(2S)-2-hydroxy-2-(4-hydroxyphenyl)ethyl]-3-(4-hydroxyphenyl)prop-2-enamide. Hub targets included AURKA, CCNA2, CCNB1, CDK1, CHEK1, KIF11, NEK2, PLK1, TTK, and TYMS. Among these, CDK1, CHEK1, and PLK1 demonstrated both high-prognostic relevance and strong binding affinity with SMS, emerging as core regulatory targets for SMS in LUAD treatment. Mechanistically, SMS exerts its anticancer effects primarily by modulating the tumor necrosis factor, interleukin-17, cell cycle, and Lipid and atherosclerosis signaling pathways. The active components of SMS, such as paprazine, may exert antitumor effects partly through downregulating CDK1, CHEK1, and PLK1 expression. Although the present study did not examine drug-resistance models or combination regimens, our findings raise the possibility that, in patients with high expression of these genes, combining SMS with standard chemotherapy or targeted therapy could potentially enhance chemosensitivity and mitigate the development of resistance. This hypothesis, however, requires formal testing in appropriate preclinical models and functional validation studies.

Molecular Dynamics Simulation

The chemical constituents of ginseng plants.

The dried roots and rhizomes of ginseng (P. ginseng C. A. Meyer) contain many physiologically important constituents. These include ginseng saponins, ginseng oils and phytosterol, carbohydrates and sugars, organic acids, nitrogenous substances, amino acids and peptides, vitamins and minerals, and certain enzymes that have been isolated and characterized. Among these, ginseng saponins are proven to be the principal and most active constituents. Chemical research, therefore, has been focused on these saponins--their extraction, purification, identification, isolation of aglycones (genins), and biosynthesis. So far 13 saponins have been isolated and identified and these, which have been called ginsenosides or panaxosides, are triterpenes of dammarane and oleanane structures. Although American, Japanese, San-ch'i, Himalayan, and Siberian ginseng roots contain many saponins similar to those found in ginseng, the overall components in these ginseng species are quite different. The above-ground parts, particularly the leaves, of these ginseng plants contain many of the saponins normally present in the roots. The search for economical sources of ginseng saponins from nature and even chemical synthesis may likely become the active ginseng research of the future. Continued, meticulous studies are undoubtedly needed to develop these natural panacea into useful, efficacious modern remedies.

Acids

Effects of the first (ether) extract of ginseng on the cardiovascular dynamics of dogs during halothane anesthesia.

An electromagnetic flowmeter probe was chronically implanted around the ascending aorta in ten dogs. Subsequently, these animals were maintained under halothane (0.75%) anesthesia during the intravenous administration of an ether extract (40 mg/kg) of ginseng. Five other dogs were anesthetized without injecting ginseng. Eleven cardiovascular variables including cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure, total peripheral resistance, pH, PaCO2, PaO2 and base deficit were compared during the ensuing 120 minutes. The heart rate was significantly decreased and central venous pressure increased significantly following ginseng. There were no other meaningful changes in either group.

Anesthesia

Effects of the second (ethanol) extract of ginseng on the cardiovascular dynamics of dogs during halothane anesthesia.

An electromagnetic flowmeter probe was chronically implanted around the ascending aorta in a group of dogs. Subsequently, ten dogs were lightly anesthetized with halothane (0.75%), and a second (ethanol) extract of ginseng (40 mg/kg) was administered intravenously. Five dogs were anesthetized without the administration of ginseng. Eleven cardiovascular variables including cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure, total peripheral resistance, pH, PaCO2, PaO2, and base deficit were compared for two hours. The heart rate and mean arterial pressure were significantly decreased following ginseng. There were no other meaningful changes in either group.

Anesthesia, Inhalation

Effects of the third (aqueous) extract of ginseng on the cardiovascular dynamics of dogs during halothane anesthesia.

An electromagnetic flowmeter probe was chronically implanted around the ascending aorta in a group of dogs. Subsequently, ten dogs were lightly anesthetized with halothane (0.75%) and the third (aqueous) extract of ginseng (40 mg/kg) was administered intravenously. Five dogs were anesthetized without the administration of ginseng. Eleven cardiovascular variables including cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure, total peripheral resistance, pH, PaCO2, PaO2, and base deficit were compared. The cardiac output, stroke volume, and central venous pressure were decreased significantly, while total peripheral resistance was increased significantly following ginseng.

Anesthesia, Inhalation

The effect of ginseng on lifespan and stress responses in mice.

It has been suggested that ginseng can increase long-term resistance to stress and disease and therefore affect the lifespan. We set out to investigate this idea by testing whether the continuous administration of ginseng could affect the lifespan of mice and/or their behavioural responses to stress. 270 mice of strain LACa were divided into three groups: one group which was given ginseng from 8 weeks of age, a second group which was given ginseng from 52 weeks of age and an untreated control group. The mice were generally healthy. Their weights remained stable throughout their lifespan and were not altered by ginseng. Ginseng administration did not significantly alter the lifespan. However, ginseng did cause an exaggeration of the behavioural responses to mild stress. This effect was noticeable soon after ginseng administration and subsequently was maintained.

Animals