Search Results (28)

Panax notoginseng, a high-value medicinal crop, suffers substantial yield losses due to Fusarium oxysporum-mediated root rot, for which no molecularly defined control targets are currently available. Histone acetyltransferases (HATs) serve as crucial epigenetic regulators of fungal development and stress responses; however, their functional roles in F. oxysporum remain largely unexplored. In this study, we systematically identified six FoHAT genes via genome-wide analysis and classified them into evolutionarily conserved subfamilies through phylogenetic comparison with orthologs from Saccharomyces cerevisiae, Homo sapiens, and Arabidopsis thaliana. Structural analyses revealed distinct motif compositions and domain architectures among FoHAT members, while promoter cis-element profiling suggested potential subfunctionalization via stress-responsive regulatory mechanisms. Functional investigations demonstrated that major notoginsenosides present in P. notoginseng root exudates—R₁, Rg₁, Rg₂, Re, and Rd—dynamically influenced both spore germination and FoHAT expression profiles. Intriguingly, each notoginsenoside exerted concentration-dependent non-linear effects on spore germination, either inhibiting or promoting the process. Concurrently, notoginsenoside exposure triggered compensatory transcriptional responses, most notably a rebound in Fo-Hat1_N expression from 9% to 112% under Rd treatment. This work establishes an initial epigenetic framework for combating Fusarium root rot in medicinal plants and offers a foundation for developing HAT-targeted small-molecule inhibitors. Full article

Background: Given the need to optimize Panax notoginseng cultivation, screen high-quality germplasm, and clarify its insufficiently elucidated genetic–phenotype–quality associations (e.g., saponin accumulation), this study was conducted. Methods: Agronomic traits were measured, saponin accumulation was determined via high-performance liquid chromatography (HPLC), and comprehensive performance was evaluated through integrated cluster analysis and fuzzy membership function assessment; additionally, single-nucleotide polymorphism (SNP)-based genetic diversity analysis was conducted to explore the genetic basis of trait variations. Results: Agronomic traits exhibited coefficients of variation (CVs) of 2.95–18.12%, with primary root length showing the highest variability. Phenotypic cluster analysis divided the materials into three groups. Group I (“Miaoxiang No.1”, “Dianqi No.1”, “Miaoxiang Kangqi No.1”) was characterized by tall plants, sturdy stems, heavy roots, and long/large leaves. Saponin determination results revealed significant differences in notoginsenoside R1, ginsenoside Rb1, ginsenoside Re, ginsenoside Rd, and total saponins among cultivars (order: “Zijing” > “Dianqi No.1” > original cultivar > “Miaoxiang Kangqi No.1” > “Miaoxiang No.1” > “Miaoxiang No.2”), with “Zijing” having the highest total saponin accumulation (18.13%); no significant difference was observed in ginsenoside Rg1 accumulation. The GATK initially identified 16,329,600 SNPs, and 115,930 high-quality SNPs were retained after Samtools filtration. SNP-based Neighbor-joining (NJ) clustering grouped the cultivars into three categories, with the original cultivar clustered alone as one category. Through comprehensive evaluation, three superior germplasm lines (“Miaoxiang Kangqi No.1”, “Miaoxiang No.1”, “Dianqi No.1”) were identified. A significant negative correlation (p < 0.05) was found between compound leaf petiole length and saponin accumulation. Conclusions: This integrated analytical strategy clarifies the links between genetics, phenotype, and quality, providing a scientific foundation for P. notoginseng germplasm screening and facilitating future molecular breeding efforts. Full article

Development of paclitaxel-induced neuropathic pain (PINP) during chemotherapy may lead to paclitaxel discontinuation, potentially compromising effective anticancer therapy. PINP can manifest as allodynia. One recently discovered key factor in paclitaxel-induced mechanical allodynia (PIMA) pathogenesis is the elevated activity of monoacylglycerol lipase (MAGL), an enzyme that metabolizes the endocannabinoid 2-arachidonoylglycerol (2-AG). Thus, inhibiting MAGL serves as a potential analgesic target. Notoginsenoside R1 (NGR1), a metabolite of Panax notoginseng, has shown promise in reducing oxidative stress and neuronal apoptosis in nerve injury models. However, its effects on PIMA and MAGL activity have not yet been explored. This study is a proof-of-concept preclinical study investigating the antiallodynic effects of NGR1 on PIMA in female BALB/c mice and also examining its effect on MAGL activity. The effect of treatment of mice with NGR1 intraperitoneally on the development of PIMA was evaluated. Molecular docking using CB-Dock2 compared the binding energies to MAGL of NGR1 and pristimerin, a triterpene MAGL inhibitor. The effects of NGR1 on human recombinant MAGL activity, as well as the MAGL activity in mice paw skin tissues, were assessed using MAGL inhibitor screening and MAGL activity assay kits, respectively. NGR1 prevented the development of PIMA in a dose-dependent manner. The docking scores showed that NGR1 has a good affinity for MAGL (−7.8 kcal/mol, binding energy) but less affinity than pristimerin (−10.3 kcal/mol). NGR1 inhibited the human recombinant MAGL activity in a reversible and concentration-dependent manner, although the inhibition was in a reverse order. Treatment of mice with NGR1 showed a non-significant trend in reducing the paclitaxel-induced increase in MAGL activity in the paw skin. This study shows for the first time that NGR1 prevents the development of PIMA and suggests that NGR1 has affinity for and inhibits human recombinant MAGL activity with a paradoxical inhibition pattern. More mechanistic studies are needed to fully elucidate the molecular mechanisms of NGR1 in preventing PIMA. Full article

The genus Panax contains traditional herbs that have been widely used in traditional medicine. The active constituents, collectively known as ginsenosides, are well characterized in the most representative species, P. notoginseng. However, the major bioactive chemical constituents of P. stipuleanatus together with P. vietnamensis are relatively less studied. In this study, an untargeted metabolomic analysis was performed in P. notoginseng, P. stipuleanatus, and P. vietnamensis using root and leaf organs. Further metabolomic differences in P. stipuleanatus were compared with those of the two most prevalent species. The analysis results revealed tissue-specific qualitative and quantitative metabolic differences in each species. Several differentially accumulated metabolites were enriched in the biosynthesis of secondary metabolites, including the biosynthesis of ginsenosides I. The ginsenosides Rb1, Rf, Rg1, Rh1, Rh8, and notoginsenosides E, M, and N had a higher abundance level in the roots of both P. notoginseng and P. vietnamensis. In P. stipuleanatus, the accumulation of potentially important ginsenosides is mainly found in the leaf. In particular, the dammarane-type ginsenosides Rb3, Rb1, Mx, and F2 as well as the notoginsenosides A, Fe, Fa, Fd, L, and N were identified to have a higher accumulation in the leaf. The strong positive correlation network of different ginsenosides probably enhanced secondary metabolism in each species. The comparative analysis revealed a significant differential accumulation of metabolites in the leaves of both species. The various compounds of dammarane-type ginsenoside, such as Rb1, Rg1, Rg6, Rh8, Rh10, Rh14, and majoroside F2, had a significantly higher concentration level in the leaves of P. stipuleanatus. In addition, several notoginsenoside compounds such as A, R1, Fe, Fd, and Ft1 showed a higher abundance in the leaf. These results show that the abundance level of major ginsenosides is significant in P. stipuleanatus and provides an important platform to improve the ginsenoside quality of Panax species. Full article

Mitochondrial homeostasis is crucial for maintaining cellular energy production and preventing oxidative stress, which is essential for overall cellular function and longevity. Mitochondrial damage and dysfunction often occur concomitantly in myocardial ischemia–reperfusion injury (MIRI). Notoginsenoside R1 (NGR1), a unique saponin from the traditional Chinese medicine Panax notoginseng, has been shown to alleviate MIRI in previous studies, though its precise mechanism remains unclear. This study aimed to elucidate the mechanisms of NGR1 in maintaining mitochondrial homeostasis in hypoxia/reoxygenation (H/R) H9c2 cells. The results showed that NGR1 pretreatment effectively increased cell survival rates post-H/R, reduced lactate dehydrogenase (LDH) leakage, and mitigated cell damage. Further investigation into mitochondria revealed that NGR1 alleviated mitochondrial structural damage, improved mitochondrial membrane permeability transition pore (mPTP) persistence, and prevented mitochondrial membrane potential (Δψm) depolarization. Additionally, NGR1 pretreatment enhanced ATP levels, increased the activity of mitochondrial respiratory chain complexes I–V after H/R, and reduced excessive mitochondrial reactive oxygen species (mitoROS) production, thereby protecting mitochondrial function. Further analysis indicated that NGR1 upregulated the expression of mitochondrial biogenesis-related proteins (PGC-1α, Nrf1, Nrf2) and mitochondrial fusion proteins (Opa1, Mfn1, Mfn2), while downregulating mitochondrial fission proteins (Fis1, Drp1) and reducing mitochondrial autophagy (mitophagy) levels, as well as the expression of mitophagy-related proteins (Pink1, Parkin, BNIP3) post-H/R. Therefore, this study showed that NGR1 can maintain mitochondrial homeostasis by regulating mitophagy, mitochondrial fission–fusion dynamics, and mitochondrial biogenesis, thereby alleviating H9c2 cell H/R injury and protecting cardiomyocytes. Full article

Cisplatin-induced ototoxicity occurs in approximately half of patients treated with cisplatin, and pediatric patients are more likely to be affected than adults. The oxidative stress elicited by cisplatin is a key contributor to the pathogenesis of ototoxicity. Notoginsenoside R1 (NGR1), the main bioactive compound of Panax notoginseng saponins, has antioxidant and antiapoptotic effects. This study investigated the ability of NGR1 to protect against cisplatin-induced damage in auditory HEI-OC1 cells and neonatal murine cochlear explants. The viability of HEI-OC1 cells treated with NGR1 and cisplatin was greater than that of cells treated with cisplatin alone. The results of Western blots and immunostaining for cleaved caspase-3 revealed that the level of cleaved caspase-3 in the cells treated with cisplatin was repressed by NGR1. NGR1 attenuated cisplatin-induced cytotoxicity in HEI-OC1 cells. Intracellular reactive oxygen species (ROS) were detected with a DCFDA assay and immunostaining for 4-HNE. The result revealed that its expression was induced by cisplatin and was significantly reduced by NGR1. Moreover, NGR1 can promote heme oxygenase-1 (HO-1) expression at both the mRNA and protein levels. ZNPPIX, an HO-1 inhibitor, was administered to cisplatin-treated cells to investigate the role of HO-1 in the protective effect of NGR1. The suppression of HO-1 activity by ZNPPIX markedly abolished the protective effect of NGR1 on cisplatin-treated cells. Therefore, NGR1 protects cells from cisplatin-induced damage by activating HO-1 and its antioxidative activity. In cochlear explants, NGR1 protects cochlear hair cells and attenuates cisplatin-induced ototoxicity by inhibiting ROS generation. In the group treated with cisplatin alone, prominent loss of outer hair cells and severe damage to the structure of the stereociliary bundles of inner and outer hair cells were observed. Compared with the group treated with cisplatin alone, less loss of outer hair cells (p = 0.009) and better preservation of the stereociliary bundles of hair cells were observed in the group treated with cisplatin and NGR1. In conclusion, these findings indicate that NGR1 can protect against cisplatin-induced ototoxicity by inducing HO-1 expression and suppressing oxidative stress. Full article

Naodesheng Tablet (Naodesheng Pian), a traditional Chinese medicine formula for stroke treatment, is made up of five herbal medicines, i.e., Sanqi, Gegen, Honghua, Shanzha, and Chuanxiong. However, the current Pharmacopoeia quality-marker (Q-marker) system cannot detect possible adulteration. Our study tried to use a new strategy, i.e., standards-library-dependent ultra-high-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry (UHPLC-Q-Orbitrap MS/MS) putative identification, to reconstruct the Q-marker system. Through the strategy, 30 isomers were successfully differentiated (such as 2′-hydroxygenistein, luteolin, and kaempferol; ginsenoside Rg2 and ginsenoside Rg3; ginsenoside Rf and ginsenoside Rg1). In particular, 11 compounds were unexpectedly found in Naodesheng, including 2′-hydroxygenistein, 7,4′-dihydroxyflavone, pectolinarigenin, 7-methoxy-4′-hydroxyisoflavone, scoparone, matrine, 3,3′,4′,5,6,7,8-heptamethoxyflavone, 5-hydroxyflavone, diosgenin, chloesteryl acetate, and (+)-4-cholesten-3-one. In total, 68 compounds were putatively identified and fully elucidated for their MS spectra. Subsequently, relevant compounds were further investigated using UV-vis scanning experiments, semi-quantitative analysis, and quantum chemical calculation. Finally, five adulterated Naodesheng Tablets were used for validation experiments. The experiment successfully detected five adulterated ones via a lower-version LC-MS analysis. On this basis, three new candidates (hydroxy safflor yellow A (HSYA), citric acid, and levistilide A), along with puerarin and notoginsenoside R1, are re-nominated as the Q-markers for LC-MS analysis. The LC-MS analysis of puerarin, notoginsenoside R1, HSYA, citric acid, and levistilide A can clearly detect adulteration regarding all five herbal medicines mentioned above. Therefore, the reconstructed Q-markers are described as a “perfect” quality control system to detect adulteration in Naodesheng and will offer a valuable recommendation for the Pharmacopoeia Commission. Full article

Ginseng Radix et Rhizoma Rubra (Panax ginseng C.A. Mey, Hongshen, in Chinese) and Ophiopogonis Radix (Ophiopogon japonicus (L.f) Ker-Gawl., Maidong, in Chinese) are traditional Chinese herbal pairs, which were clinically employed to enhance the immune system of cancer patients. This study employed the pharmacokinetic and pharmacodynamic (PK–PD) spectrum-effect association model to investigate the antitumor active substances of P. ginseng and O. japonicus (PG–OJ). The metabolic processes of 20 major bioactive components were analyzed using Ultra-Performance Liquid Chromatography–Mass Spectrometry/Mass Spectrometry (UPLC–MS/MS) in the lung tissue of tumor-bearing mice treated with PG–OJ. The ELISA method was employed to detect the levels of TGF-β1, TNF-α, and IFN-γ in the lung tissue of mice at various time points, and to analyze their changes after drug administration. The results showed that all components presented a multiple peaks absorption pattern within 0.083 to 24 h post-drug administration. The tumor inhibition rate of tumor and repair rate of IFN-γ, TNF-α, and TGF-β1 all increased, indicating a positive therapeutic effect of PG–OJ on A549 tumor-bearing mice. Finally, a PK–PD model based on the GBDT algorithm was developed for the first time to speculate that Methylophiopogonanone A, Methylophiopogonanone B, Ginsenoside Rb₁, and Notoginsenoside R1 are the main active components in PG–OJ for lung cancer treatment. Full article

Panax notoginseng (P. notoginseng) has excellent medicinal and food dual-use characteristics. However, P. notoginseng with a unique origin label has become the target of fraud because of people confusing or hiding its origin. In this study, an untargeted nuclear magnetic resonance (NMR)-based metabolomics approach was used to discriminate the geographical origins of P. notoginseng from four major producing areas in China. Fifty-two components, including various saccharides, amino acids, saponins, organic acids, and alcohols, were identified and quantified through the NMR spectrum, and the area-specific geographical identification components were further screened. P. notoginseng from Yunnan had strong hypoglycemic and cardiovascular protective effects due to its high acetic acid, dopamine, and serine content, while P. notoginseng from Sichuan was more beneficial for diseases of the nervous system because of its high content of fumarate. P. notoginseng from Guizhou and Tibet had high contents of malic acid, notoginsenoside R1, and amino acids. Our results can help to distinguish the geographical origin of P. notoginseng and are readily available for nutritional recommendations in human consumption. Full article

The Panax L. genus is well-known for many positive physiological effects on humans, with major species including P. ginseng, P. quinquefolius, P. notoginseng, P. japonicus, and P. japonicus var. major, the first three of which are globally popular. The combination of UPLC-QTOF-MS and chemometrics were developed to profile “identification markers” enabling their differentiation. The establishment of reliable biomarkers that embody the intrinsic metabolites differentiating species within the same genus is a key in the modernization of traditional Chinese medicine. In this work, the metabolomic differences among these five species were shown, which is critical to ensure their appropriate use. Consequently, 49 compounds were characterized, including 38 identified robust biomarkers, which were mainly composed of saponins and contained small amounts of amino acids and fatty acids. VIP (projection variable importance) was used to identify these five kinds of ginseng. In conclusion, by illustrating the similarities and differences between the five species of ginseng with the use of an integrated strategy of combining UPLC-QTOF-MS and multivariate analysis, we provided a more efficient and more intelligent manner for explaining how the species differ and how their secondary metabolites affect this difference. The most important biomarkers that distinguished the five species included Notoginsenoside-R₁, Majonoside R₁, Vinaginsenoside R₁₄, Ginsenoside-Rf, and Ginsenoside-Rd. Full article

Panax notoginseng (Burk) F. H. Chen is a traditional Chinese medicinal and edible plant. However, Panax notoginseng flower (PNF) is rarely used. Therefore, the purpose of this study was to explore the main saponins and the anti-inflammatory bioactivity of PNF saponins (PNFS). We explored the regulation of cyclooxygenase 2 (COX–2), a key mediator of inflammatory pathways, in human keratinocyte cells treated with PNFS. A cell model of UVB-irradiation-induced inflammation was established to determine the influence of PNFS on inflammatory factors and their relationship with LL–37 expression. An enzyme-linked immunosorbent assay and Western blotting analysis were used to detect the production of inflammatory factors and LL37. Finally, liquid chromatography–tandem mass spectrometry was employed to quantify the main active components (ginsenosides Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1, and notoginsenoside R1) in PNF. The results show that PNFS substantially inhibited COX–2 activity and downregulated the production of inflammatory factors, indicating that they can be used to reduce skin inflammation. PNFS also increased the expression of LL-37. The contents of ginsenosides Rb1, Rb2, Rb3, Rc, and Rd in PNF were much higher than those of Rg1, and notoginsenoside R1. This paper provides data in support of the application of PNF in cosmetics. Full article

Panax notoginseng (Burk.) F. H. is a genuine medicinal material in Yunnan Province. As accessories, P. notoginseng leaves mainly contain protopanaxadiol saponins. The preliminary findings have indicated that P. notoginseng leaves contribute to its significant pharmacological effects and have been administrated to tranquilize and treat cancer and nerve injury. Saponins from P. notoginseng leaves were isolated and purified by different chromatographic methods, and the structures of 1–22 were elucidated mainly through comprehensive analyses of spectroscopic data. Moreover, the SH-SY5Y cells protection bioactivities of all isolated compounds were tested by establishing L-glutamate models for nerve cell injury. As a result, twenty-two saponins, including eight dammarane saponins, namely notoginsenosides SL₁-SL₈ (1–8), were identified as new compounds, together with fourteen known compounds, namely notoginsenoside NL-A₃ (9), ginsenoside Rc (10), gypenoside IX (11), gypenoside XVII (12), notoginsenoside Fc (13), quinquenoside L₃ (14), notoginsenoside NL-B₁ (15), notoginsenoside NL-C₂ (16), notoginsenoside NL-H₂ (17), notoginsenoside NL-H₁ (18), vina-ginsenoside R₁₃ (19), ginsenoside II (20), majoroside F₄ (21), and notoginsenoside LK₄ (22). Among them, notoginsenoside SL₁ (1), notoginsenoside SL₃ (3), notoginsenoside NL-A₃ (9), and ginsenoside Rc (10) showed slight protective effects against L-glutamate-induced nerve cell injury (30 µM). Full article

American ginseng (Panax quinquefolius L.) has been recognized as a valuable herb medicine, and ginsenosides are the most important components responsible for the health-beneficial effects. This study investigated the secondary metabolites responsible for the differentiation of wild and cultivated American ginsengs with ultrahigh-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)-based metabolomic approach. An in-house ginsenoside library was developed to facilitate data processing and metabolite identification. Data visualization methods, such as heatmaps and volcano plots, were utilized to extract discriminated ion features. The results suggested that the ginsenoside profiles of wild and cultivated ginsengs were significantly different. The octillol (OT)-type ginsenosides were present in greater abundance and diversity in wild American ginsengs; however, a wider distribution of the protopanaxadiol (PPD)-and oleanolic acid (OA)-type ginsenosides were found in cultivated American ginseng. Based on the tentative identification and semi-quantification, the amounts of five ginsenosides (i.e., notoginsenoside H, glucoginsenoside Rf, notoginsenoside R1, pseudoginsenoside RT2, and ginsenoside Rc) were 2.3–54.5 fold greater in wild ginseng in comparison to those in their cultivated counterparts, and the content of six ginsenosides (chicusetsusaponin IVa, malonylginsenoside Rd, pseudoginsenoside Rc1, malonylfloralginsenoside Rd6, Ginsenoside Rd, and malonylginsenoside Rb1) was 2.6–14.4 fold greater in cultivated ginseng compared to wild ginseng. The results suggested that the in-house metabolite library can significantly reduce the complexity of the data processing for ginseng samples, and UHPLC-HRMS is effective and robust for identifying characteristic components (marker compounds) for distinguishing wild and cultivated American ginseng. Full article

Panax notoginseng flowers have the highest content of saponins compared to the other parts of Panax notoginseng, but minor ginsenosides have higher pharmacological activity than the main natural ginsenosides. Therefore, this study focused on the transformation of the main ginsenosides in Panax notoginseng flowers to minor ginsenosides using the fungus of Cladosporium xylophilum isolated from soil. The main ginsenosides Rb₁, Rb₂, Rb₃, and Rc and the notoginsenoside Fa in Panax notoginseng flowers were transformed into the ginsenosides F₂ and Rd₂, the notoginsenosides Fd and Fe, and the ginsenoside R₇; the conversion rates were 100, 100, 100, 88.5, and 100%, respectively. The transformation products were studied by TLC, HPLC, and MS analyses, and the biotransformation pathways of the major ginsenosides were proposed. In addition, the purified enzyme of the fungus was prepared with the molecular weight of 66.4 kDa. The transformation of the monomer ginsenosides by the crude enzyme is consistent with that by the fungus. Additionally, three saponins were isolated from the transformation products and identified as the ginsenoside Rd₂ and the notoginsenosides Fe and Fd by NMR and MS analyses. This study provided a unique and powerful microbial strain for efficiently transformating major ginsenosides in P. notoginseng flowers to minor ginsenosides, which will help raise the functional and economic value of the P. notoginseng flower. Full article