Panax notoginseng, an important traditional Chinese medicine with a long history of clinical application, possesses significant pharmacological value. P. notoginseng quality improvement has been extensively studied by chemical transformation methods; however, the bio-transformation method with beneficial microbes remains relatively underexplored. In this study, we first fermented P. notoginseng roots with the golden flower fungus Aspergillus cristatus, and then high-performance liquid chromatography (HPLC) was performed to reveal ginsenoside alterations in fungal treatment. To elucidate the underlying mechanisms, integrated transcriptome and metabolome methods were used to identify the differentially expressed genes of A. cristatus and the differentially accumulated metabolites in P. notoginseng roots after fermentation. Our study demonstrated that the P. notoginseng pharmacological compounds were dramatically changed, and the content of several important characteristic saponins, including ginsenosides R1, Re, Rb1, Rd, and Rf, was significantly increased. Concurrently, several metabolites associated with medicinal function were also significantly increased. These data further revealed the molecular characteristics of the beneficial fungus A. cristatus upon fermentation on the medicinal plant P. notginseng by reprogramming and activating fungal transcripts in the ribosome and oxidative phosphorylation-related events. This study provides new insights into the molecular mechanisms underlying A. cristatus-mediated enhancement of bioactive constituents in P. notoginseng, and establish a biotechnological foundation for improving the quality of cultivated P. notoginseng roots by controlled fermentation.
Polygonatum cyrtonema Hua is a medicinal plant valued for its dried, fleshy rhizomes. Market demand for Rhizoma Polygonati has surged due to its widespread use in health supplements and treatments for conditions such as diabetes and aging. Our field experiments demonstrated that intercropping P. cyrtonema in Xiangxi golden tea No. 2 gardens can increase farmers' income, achieving a dual harvest with enhanced yield and economic returns. This novel intercropping system has delivered improved social, ecological, and economic benefits. Therefore, we further explored the scientific mechanisms by comparing the rhizosphere microbiome diversity and its correlation with soil properties and tea quality under traditional monoculture and intercropping systems. Rhizosphere metagenomics revealed an altered microbial community structure, notably enriched abundances of Bacillus and Westerdykella, which correlated positively with a 15% increase in tea polyphenol content relative to monocultures. Intercropping also enhanced soil nutrient use efficiency for nitrogen, phosphorus, and potassium. These findings indicate that integrating P. cyrtonema into tea production systems improves both product quality and ecosystem function, offering an evidence-based strategy for sustainable agriculture.
Radiation enteritis, a complication following cancer radiotherapy, is caused by reactive oxygen species (ROS)-mediated oxidative damage, coupled with inflammatory dysregulation and disruption of the gut microbiota. Recent advancements in phytotherapy have highlighted the potential application of plant-derived bioactive compounds (e.g., curcumin from Curcuma longa, epigallocatechin gallate [EGCG], and resveratrol) as mitigators in treating radiation-induced intestinal injury. These compounds, characterized by potent ROS-scavenging activity, excellent biocompatibility, and minimal toxicity, exhibit promising attributes for therapeutic intervention. To better understand the botanical diversity and underlying mechanisms of radiation enteritis, this review systematically profiles the alkaloid-, flavonoid-, and polyphenol-rich medicinal plants, relevant bioactive constituents, and their associated therapeutic effects in synergistic modulation of oxidative, inflammatory, and apoptotic cascades. These natural compounds effectively leverage dual antioxidant mechanisms, including direct ROS scavenging via phenolic hydroxyl groups, indirect activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1), upregulation of endogenous antioxidants, suppression of pro-inflammatory cytokines, and enhancement of tight junction proteins for barrier repair. Despite their potential as adjuvant therapies, challenges remain in identifying exact antioxidant targets and translating these into clinical applications. To address this issue, we propose a framework that integrates phytochemistry, multi-omics profiling, and AI-enabled prediction of antioxidant targets. This review aims to facilitate the development of plant-based radioprotectants as next-generation adjuvant therapies.
Medicinal plant cultivation confronts distinct challenges, including soil degradation from continuous cropping, diminished regional specificity, and heavy metal contamination, all of which compromise both biomass yield and accumulation of bioactive compounds. Microbial inoculants represent a sustainable strategy to enhance medicinal plants' productivity and quality through improved nutrient uptake and stress tolerance, alongside promotion of secondary metabolite biosynthesis. This review systematically examines the mechanisms through which microbial inoculants regulate plant development, enhance stress resistance, and stimulate bioactive compound synthesis. We emphasize organ-specific application approaches tailored to root, leaf, and flower/fruit medicinal species, and explore advances in alleviating continuous cropping obstacles and reinforcing region-specific microecosystems. Key factors affecting inoculant performance are also identified, including the microbial consortium's composition, carrier materials, soil characteristics, and host genetics. Though significant progress has been made, challenges related to colonization stability and mechanistic clarity persist. Future prospects involve developing synthetic microbial communities, integrating multi-omics technologies, and designing smart delivery systems to advance ecological cultivation practices. This review highlights the potential of microbial inoculants in supporting sustainable production of high-quality medicinal plants while minimizing environmental footprints.
Ganoderic acids are the primary bioactive constituents of the medicinal fungus Ganoderma lucidum. Commercial cultivars typically have low ganoderic triterpenoid contents, creating an urgent industry need for high-triterpenoid germplasm. Here, we developed an efficient breeding pipeline for G. lucidum using protoplasts of strain 'Xianzhi No. 2' subjected to sodium azide (SA) mutagenesis, followed by antagonistic screening and total triterpenoid quantification to identify elite mutants. SA concentrations of 0-5 mM were tested, and 2 mM was selected as the half-lethal dose (53.30% +/- 8.61% protoplast survival after 3 h treatment) for mutant library construction. Mutagenized isolates were categorized into five categories (I-V)by antagonistic phenotype. From 4,839 colonies, 217 with distinct antagonistic traits, and 259 randomly selected non-antagonistic isolates were cultivated for fruiting body production, yielding 275 fruiting-competent mutants. Quantitative analysis revealed that the high-yield mutant TT89 had a total triterpenoid content of 4.40%, a 262.27% increase over the wild-type (1.68% content). We also identified mutants with significantly reduced triterpenoid levels, including the non-antagonistic strain X16, which contained only 16.34% of the wild-type's triterpenoid content. This is the first report of an integrated breeding system for G. lucidum combining SA mutagenesis, antagonistic prescreening, and triterpenoid quantification. Our findings validate SA as an effective mutagen for G. lucidum and provide valuable mutant resources and technical support for germplasm improvement and triterpenoid biosynthesis research.
Heat shock protein 70 (HSP70) plays crucial roles in plants' responses to abiotic stresses. In this study, we performed a genome-wide identification and comprehensive characterization of the HSP70 gene family in the medicinal herb Pinellia ternata. In total, 21 PtHSP70 genes were identified and classified into distinct subfamilies via phylogenetic analysis. Structural and motif analyses revealed conserved domain architectures, whereas promoter examination indicated the enrichment of stress-and hormone-responsive cis-elements. Ka/Ks and collinearity analyses indicated that the PtHSP70 genes have primarily evolved under purifying selection and share extensive synteny with orthologs in related monocot species. Expression profiling revealed that most PtHSP70 genes were significantly upregulated in response to both heat (35 degrees C) and cold (8 degrees C) stress. The result of tissue-specific expression showed most PtHSP70 genes were highly expressed in the tubers. PtHSP70 genes responded differentially to methyl jasmonate (MeJA) and abscisic acid (ABA) treatments, with five PtHSP70 genes being significantly upregulated by both ABA and MeJA. Our findings provide a foundation for further functional studies of PtHSP70 genes in abiotic stress tolerance and offer valuable insights for molecular improvement of P. ternata.
Angelica sinensis (Oliv.) Diels is a valuable medicinal plant whose dried roots are widely used in traditional Chinese medicine for blood enrichment and nourishment. NAC transcription factors (TFs) are known to play central roles in plant growth, secondary metabolism, and lignin biosynthesis. Here, we identified 122 AsNAC TFs from the A. sinensis genome. Phylogenetic analysis using NAC proteins from Arabidopsis thaliana, combined with expression profiling, identified AsNAC043 as a key candidate regulator. Subcellular localization confirmed that AsNAC043 localizes specifically to the nucleus, consistent with its function as a TF. We subsequently constructed an AsNAC043-overexpressing transgenic line in A. sinensis callus. Overexpression of AsNAC043 resulted in a significant increase in lignin content. Transcriptomic analysis further revealed upregulation of several key lignin biosynthesis genes, including AsCCR and AsCADs. Our results demonstrate that AsNAC043 may promote lignin accumulation in A. sinensis by activating the expression of core lignin biosynthesis genes. These findings provide insight into the molecular mechanism of AsNAC-mediated lignin biosynthesis, and offer valuable targets and theoretical support for breeding high-quality A. sinensis varieties.
As a crucial medicinal group in Paeoniaceae, Paeonia plants are rich in bioactive monoterpenoids and phenolic compounds (e.g., paeoniflorin, paeonol, and flavonoids) in their roots, flowers, and other parts. They serve as core medicinal resources in traditional Chinese medicine (TCM) for nourishing blood, activating blood circulation, alleviating inflammation, and relieving pain. In recent years, in-depth studies have clearly elucidated the molecular mechanisms of these bioactive components. With breakthroughs in whole-genome sequencing, transcriptomics, and metabolomics technologies, over 100 secondary metabolites in Paeonia plants has been accurately identified, and multiple pharmacological mechanisms have been analyzed. This review systematically summarizes the current status of Paeonia plants in terms of plant resources, the exploration of bioactive components, analysis of the pharmacological mechanisms, and development/utilization. Combined with the cutting-edge progress in multi-omics technologies and synthetic biology, this review indicates the key directions of Paeonia in innovative drug research and development, aiming to provide a theoretical reference and technical support for the in-depth development of this group of medicinal plants.
Scrophularia ningpoensis relies mainly on vegetative propagation, a practice that can accelerate germplasm degradation and pathogen accumulation, thereby limiting the large-scale production of healthy seedlings. Here, we established an in vitro regeneration system using leaf and petiole explants cultured on Murashige and Skoog (MS) medium supplemented with different combinations of 6-benzylaminopurine (6-BA) and naphthaleneacetic acid (NAA), and applied machine learning (ML) to model the regeneration responses within the tested experimental space. Regeneration showed clear organ-specific patterns: Leaf explants exhibited strong rooting capacity, reaching 96.7% +/- 3.3% at 1.0 mg/L 6-BA + 1.0 mg/L NAA, whereas petiole explants showed higher shoot regeneration, with a maximum of 50.0% +/- 11.6% at 0.5 mg/L 6-BA + 0.2 mg/L NAA. Factorial analysis of variance and ordinary least squares regression identified explant type and NAA concentration as the major determinants of regeneration. Random forest models showed moderate predictive performance for shoot regeneration (R2 = 0.57) and stronger predictive performance for rooting (R2 = 0.78), with explant type consistently ranked as the most influential variable. Notably, the highest-ranked rooting condition predicted by the model was the same as the best-performing treatment identified experimentally. Together, these findings establish an efficient regeneration system for S. ningpoensis, demonstrate explant-specific responses to phytohormones, and support ML as a complementary tool for quantitative interpretation and predictive analysis of tissue culture responses in nonmodel medicinal plants.
Patchouli is a medicinal plant belonging to the Pogostemon genus within the Lamiaceae family. It is composed mainly of sesquiterpenoid metabolites, and has various pharmacological effects. The mechanism underlying the transcriptional regulation of the patchouli alcohol has been reported, but the mechanism underlying the regulation of transcription factors (TFs) involved in the sesquiterpenoid metabolic pathway is still unknown. In this study, a regulatory network was constructed for the sesquiterpenoid metabolic pathway in patchouli by using a gene expression database and WGCNA. It was found that 286 TFs have potential regulatory relationships with 28 genes that encode enzymes in the sesquiterpenoid metabolic pathway. The regulatory mechanism of this network was successfully verified by yeast one-hybrid (Y1H), dual luciferase reporter assay (dual-LUC), transient overexpression, and electrophoretic mobility shift assay (EMSA). In conclusion, a regulation network was constructed for sesquiterpenoid metabolic pathways in Pogostemon cablin, and all the TFs that may have regulatory functions in sesquiterpenoid metabolic pathways were identified, and the regulatiory functions of transcription factors were successfully verified through bench experiments.
Lonicerae japonicae flos (LJF) is a significant food and traditional Chinese medicine with diverse pharmacological effects and extensive prescription compatibility. However, systematic quality evaluation of LJF remains limited. Accurate identification of geographical origin is crucial for quality control and clinical efficacy. For the first time, this study integrates morphological quality assessment, environmental factors, and intrinsic quality characteristics by discriminate its geographical origin. Stable isotope ratios (S13C and S15N) and relative contents of the marker compounds in LJF from eight geographical regions (n = 40) were determined. Multivariate statistical analysis revealed significant original differences. Hierarchical Cluster Analysis (HCA), Principal cryptochlorogenic acid as key markers responsible for these geographical variations. Furthermore, a classification model for discriminating LJF geographical origin was developed using Linear Discriminant Analysis (LDA), and this model achieved 97.5% accuracy. This analysis elucidates the variations in stable isotopes and marker compounds, providing a valuable reference for the origin authentication, selection, and quality assessment of LJF.
Ganoderic acids (GAs) are bioactive compounds in Ganoderma lucidum that have various pharmacological properties. Their biosynthesis is influenced by environmental factors and elicitors, but the synergistic effects of multiple inducers on GA accumulation are not well understood. This study examined the effects of calcium chloride (CaCl2), phenobarbital (PB), methyl jasmonate (MeJA), and 5-azacytidine (5-AC) as exogenous inducers. The results showed GA contents of 26.35 +/- 0.67, 31.53 +/- 0.30, 24.66 +/- 0.82, and 26.61 +/- 0.37 mg/g dry weight (DW), respectively. Using Box-Behnken design (BBD) based on the response surface methodology (RSM), the optimal combination of inducers was determined to be 400.00 mu M CaCl2, 1,087.96 mu M PB, 260.67 mu M MeJA, and 823.04 mu M 5-AC (the Mix treatment), which led to a GA content of 31.94 mg/g DW, a 47.67% increase compared with the untreated control. Under 125 mu M MeJA and the Mix treatment, the contents of GA-B and GA-D increased by 121.50-and 68.94-fold, respectively. Transcriptomic analysis revealed 233, 216, 1858, 488, and 699 differentially expressed genes (DEGs) in the five treatment groups. Among them, 5, 5, 2, 6, and 5 upregulated mevalonic acid (MVA) pathway genes and 4, 7, 69, 10, and 36 Cytochrome P450 (CYP) DEGs were identified, including a common downregulated CYP gene, GLB03G000748, suggesting its role in negative regulation of GA biosynthesis. This study not only demonstrates an effective combined induction strategy for the enhanced production of GAs by G. lucidum but also, through transcriptomic analysis, provides crucial molecular insights into the regulatory mechanisms of GA biosynthesis.
Plant non-specific lipid transfer proteins (nsLTPs) are small secretory proteins that bind and transport hydrophobic molecules. nsLTPs are crucial players in various plant physiological processes, including lipid metabolism and defense. In Artemisia annua, glandular trichomes serve as the primary sites for artemisinin biosynthesis and storage. Although several nsLTPs have been reported in Artemisia annua, a comprehensive genome-wide analysis was previously lacking. In this study, 55 nsLTP genes were identified in the A. annua genome and classified into eight types (I, II, III, IV, V, VI, VII, and IX) through phylogenetic analysis. Notably, expression profiling revealed that certain AaLTP genes, especially AaLTP1 and AaLTP2, exhibit glandular trichome-specific expression, as confirmed by promoter::GUS assays. Overexpression ofAaLTP1 significantly increased artemisinin content by 1.5-fold (p < 0.05), suggesting its direct role in facilitating artemisinin accumulation. Furthermore, an HD-ZIP transcription factor, AaHD8, was confirmed as a positive regulator ofAaLTP1 and AaLTP2 through direct promoter binding. Overall, this study provides the first comprehensive characterization of the nsLTP gene family in A. annua and establishes a functional link between nsLTPs, glandular trichome biology, and artemisinin biosynthesis, offering new insights for metabolic engineering to enhance artemisinin production.
Anthracnose is an emerging threat to Epimedium sagittatum, a cornerstone species in traditional Chinese medicine; however, its etiology in biodiversity hotspots remains unresolved. In this study, we comprehensively identified the anthracnose pathogens affecting E. sagittatum in China's Shennongjia Forest District. Through a combination of multi-locus phylogenetic analyses (based on ITS2, GAPDH, TUB2, and ACT sequences) and pathogenicity assays, we identified Colletotrichum fructicola as the primary causal agent. Beyond pathogen identification, we found that infection triggers a sharp decline in key flavonoids (epimedin A, B, and C; icariin; and icaritin). Concurrent rhizosphere microbiome profiling revealed a shift toward dysbiosis, characterized by the Rhizoclosmatium, Fusarium, and Coccidioides). Strikingly, in detached leaf assays, the plant-derived phenolic compound carvacrol inhibited the growth of C. fructicola by 86.7%. Together, our findings not only identify a pathogen of concern but also delineate a disease progression pathway primarily driven by metabolic reprogramming of the host (flavonoid depletion) and concomitant rhizosphere dysbiosis. We also propose carvacrol as a potent biocontrol agent. This work addresses critical knowledge gaps in medicinal plant pathology and proposes an eco-sustainable strategy for managing anthracnose.
Ophiocordyceps sinensis (syn. DongChongXiaCao), a rare and endemic medicinal fungus native to China, possesses significant pharmacological and commercial value. However, the chemical composition, pharmacological mechanisms, and biosynthetic pathways of secondary metabolites in O. sinensis remain largely uncharacterized, hindering efforts to enhance its quality and develop derived products. This review summarizes the resource status, chemical constituents, and pharmacological properties of O. sinensis, with a focus on the omics research progress and the biosynthetic pathways of key secondary metabolites such as cordycepin, ergosterol, and polysaccharides. Modern pharmacological studies reveal that O. sinensis exhibits immunomodulatory, anti-inflammatory, antitumor, anti-aging, antihypertensive, and antioxidant activities, primarily attributed to its polysaccharides, nucleosides, sterols, and peptides. Despite advancements in omics technologies for studying its unique developmental mechanisms and secondary metabolite biosynthesis, knowledge in this field remains limited, especially compared with congeneric species. Finally, future research directions, including the development of quality biomarkers, exploration of complex macromolecules, investigation of O. sinensis-environment interactions, and artificial cultivation techniques, are proposed to alleviate resource scarcity. This review highlights current research gaps and provides actionable solutions, laying a foundation for the subsequent development of related products and the sustainable utilization of O. sinensis.
Benzylisoquinoline alkaloids (BIAs) derived from Coptis species, opium poppy, and California poppy have been demonstrated to cure various diseases. Historically, Coptis species, opium poppy, and California poppy have served as models for the study of BIAs; however, the produced BIAs in these plants are of low yield for medicinal purposes. Although the chemical synthesis approach has been adopted for large-scale production of BIAs, medicinal plants remain the only reliable platform for this purpose. With the recent advancement of high-throughput sequencing technology, genomic or transcriptomic information of Coptis chinensis, Coptis deltoidea, Coptis teeta, opium poppy, and California poppy has been available over the past decade, which has led to a comprehensive elucidation and update of the biosynthetic pathways of BIAs and regulatory mechanisms governing BIA production. The jasmonate-independent and jasmonate-dependent regulatory pathways, triggered by external elicitors, are demonstrated in this study. Overexpression of AP2/ERF transcription factor, base editing for key enzymes of tyrosine synthesis, and transport engineering in microbes are some strategies presented to provide ideas for enhancing BIAs content. This review provides a foundation for BIA accumulation in medicinal plants and de novo synthesis of BIAs in microbial hosts, thereby facilitating the discovery and development of alkaloid-based drugs.
This study investigates the secondary metabolism regulatory mechanism of the Labiatae medicinal plant Schizonepeta tenuifolia Briq. The monoterpene synthase StLS catalyzes the manufacture of (-)-pulegone, a distinctive monoterpene active component of this species, and its expression level directly impacts secondary metabolite accumulation. Due to the limited knowledge of the StLS transcriptional regulatory network, this study employed a multiomics combined analysis to investigate the role of the R2R3-MYB transcription factor in plant metabolic regulation. It was discovered that StMYB13 and StMYB76 are regulatory elements after a deep analysis of the Arabidopsis thaliana transcriptome database using bioinformatics screening. The yeast one-hybrid system (Y1H) showed that StMYB13/StMYB76 could specifically bind CAACGG in the StLS promoter region from-1,234 to-1,274 bp. Virus-induced gene silencing (VIGS) and transient overexpression were used to unveil the StMYB transcription factor's monoterpene metabolic pathway regulatory network. The transcription factor controlled the monoterpene synthase StLS's transcriptional activity and downstream biosynthetic enzyme-encoding gene expression. The silencing of StMYB genes led to a dramatic reduction (p < 0.001) in the expression of the pivotal gene StIPD, whereas the overexpression system caused a substantial elevation in its mRNA levels. Further analysis demonstrated that this regulatory process exhibits a distinct expression-level-dependent pattern: (-)-pulegone content was significantly elevated in overexpression lines, whereas no statistically significant difference in (-)-pulegone accumulation was observed in silenced groups. These findings revealed StMYBs'transcriptional regulation mechanism and provided molecular evidence for the analysis of S. tenuifolia's volatile oil synthesis nodes. This discovery deepened the monoterpene biosynthesis pathway and laid the theoretical groundwork for metabolic engineering and molecular-assisted breeding systems of S. tenuifolia.
Scutellaria baicalensis Georgi is a traditional Chinese medicinal herb that is rich in 4'-deoxyflavonoids. Galangin (4'-deoxyflavonol) is a bioactive natural product found in S. baicalensis. To date, little is known about the biosynthesis of galangin. In this study, three flavonol synthases, Sb2ODD8, Sb2ODD11, and Sb2ODD12 were characterized from S. baicalensis. They exhibited bifunctional F3H/FLS activities (predominantly FLS), converting flavanones to dihydroflavonols, and then to flavonols. Enzyme kinetics revealed that they had distinct substrate preferences: Sb2ODD11 showed higher catalytic efficiency towards pinobanksin (4'-deoxydihydroflavonol), while Sb2ODD8 and Sb2ODD12 preferred dihydrokaempferol (4'-hydroxydihydroflavonol). These findings provide insights into the biosynthesis of flavonols in S. baicalensis and offer valuable information for metabolic engineering of flavonol production.
With the rise of the big health industry, research on the active ingredients of Chinese herbal medicines has been widely considered. The secondary metabolites of medicinal plants play an important role in preventing and treating various diseases as the active components of Chinese herbal medicine. Therefore, improving the production of secondary metabolites and the quality of medicinal materials in medicinal plants has become the core of research work. Plant hormones, essential for controlling growth, development, and metabolic processes in plants, play a critical role in this regulatory mechanism. They contribute to the growth and development of medicinal plants, influence the synthesis of secondary metabolites, and regulate the synthesis of stress-related metabolites by affecting plant responses to stress. In the past, most of the attention on the effects of plant hormones was focused on regulating plant growth and development, and the metabolic regulation network of hormones on medicinal plants was relatively complex, so there were few systematic and comprehensive reports on related studies. This paper aims to summarize the regulation mechanisms and effects of various plant hormones on the secondary metabolism of medicinal plants, highlighting the intricate interactions among these hormones. It seeks to elucidate the regulatory network of plant hormones in the secondary metabolism of medicinal plants, offering a theoretical foundation for future research on improving the quality of Chinese medicinal materials.
