Search Results (67)

Background/Objectives: Tripterygium glycosides (TG) are used to treat inflammatory and autoimmune diseases, but their clinical application is limited by toxicity and the lack of process-responsive quality markers. This study examined whether roasting and dealkalization remodel the TG metabolite profile and alter the post-dose serum profile of circulating prototype constituents. Methods: Self-prepared TG, roasted TG (RTG), roasted–dealkalized TG (RDTG), and five marketed products were profiled by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Seven representative compounds were quantified by validated high-performance liquid chromatography (HPLC). Rat serum after oral administration was analyzed to compare circulating prototype constituents. Results: We characterized 243 constituents in material samples and 63 circulating prototype constituents in serum. Roasting primarily reshapes the profiles of diterpenoids and triterpenoids. Celastrol was not detected in the RTG and RDTG material samples, nor in the corresponding single-time-point serum profiles under the current analytical conditions. In contrast, wilforlide A exhibited an increase in material samples. Dealkalization preferentially reduced alkaloid-related constituents, including wilforine in material samples and tripterygiumine T in serum. Conclusions: Integrated material profiling, targeted quantification, and serum prototype analysis identified candidate process-responsive markers for processed TG preparations. Because the serum study was based on relative signal intensities rather than full pharmacokinetics, these markers require further pharmacokinetic and toxicological validation. Full article

This study investigated the effects of moisture content (80% vs. 70%) and Lactiplantibacillus plantarum inoculation on the fermentation quality, microbial community structure, and metabolite profiles of amaranth (Amaranthus hypochondriacus) silage using integrated microbiomics (full-length 16S rRNA sequencing) and untargeted metabolomics (UPLC-MS/MS). The results showed that high-moisture silage without inoculation (AhGCK) exhibited poor fermentation quality, characterized by high pH (5.09) and low lactic acid content (1.42% FM). Inoculation with L. plantarum significantly reduced pH (to 4.16) and increased lactic acid accumulation (to 3.65% FM) under high-moisture conditions. Wilting to 70% moisture combined with L. plantarum inoculation (AhSLP) achieved the best fermentation quality, with the lowest pH (4.20) and highest lactic acid (4.46% FM). Microbial community analysis revealed that Enterobacter cloacae dominated in AhGCK, whereas L. plantarum, Lentilactobacillus buchneri, and Levilactobacillus brevis became dominant after inoculation and wilting. Metabolomics identified 497 compounds across all treatments, with differential metabolites primarily enriched in pathways related to amino acid metabolism, carbohydrate metabolism, and biosynthesis of secondary metabolites such as diterpenoids and isoquinoline alkaloids. Highly significant correlations (p < 0.01) were observed between Enterobacter and cyclohexylammonium, between dTDP-3-O-methyl-β-L-rhamnose and 2-hydroxy-2H-benzo[h]chromene-2-carboxylate, between Lentilactobacillus and 3-ketosucrose (positive), and between Limosilactobacillus and 8-methylthiooctyl glucosinolate (positive), whereas Lactiplantibacillus and Escherichia Shigella showed no correlations with differential metabolites. These findings indicate that inoculating Lactobacillus plantarum at specific moisture levels (80% and 70%) promotes directed microbial community succession (as exemplified by positive correlations of Lentilactobacillus and Limosilactobacillus with beneficial metabolites) and optimized metabolite accumulation, which significantly lowers dry matter loss during fermentation and enhances the output of usable silage. This mechanism offers a practical theoretical foundation for improving amaranth silage production and boosting feed yield. Full article

The Delphinium albocoeruleum Maxim is a perennial herbaceous plant of the Ranunculaceae family, genus Delphinium. It typically grows in well-drained alpine meadows or shrublands at elevations of 2500–4000 m, which shapes the species’ unique environmental adaptation mechanism and endows it with high medicinal value. There are a few reports on the chemical constituents and biological activities of this plant. Therefore, this study focuses on the chemical constituents of the plant in order to discover structurally novel alkaloids. This paper reports on the isolation and structural characterization, using HRMS and 1D and 2D NMR, of a new alkaloid that came from the plant. Full article

Aconitum poisoning is a major public health concern in East Asia, and remains difficult to diagnose when the causative toxins are not covered by routine targeted assays. In a poisoning incident that occurred in 2018, 15 individuals were affected, including five fatalities, after accidentally consuming a medicinal tincture during a shared meal. The comprehensive alkaloid profile of the tincture implicated in the poisoning was achieved through the integration of targeted analysis, molecular networking, and untargeted screening based on ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry, aiming to clarify the causative agents. Targeted quantitative analysis detected nine alkaloids derived from Aconitum plants, confirming the presence of Aconitum ingredients in the medicinal tincture. However, these alkaloids were either present at low concentrations or exhibited low toxicity, and thus were not the principal causative agents of this poisoning incident. Molecular networking revealed additional hidden diester-diterpenoid alkaloids (DDAs) and monoester-diterpenoid alkaloids (MDAs) that were undetected by targeted analysis. Untargeted screening identified 58 Aconitum alkaloids, including 15 DDAs, 17 MDAs, 17 amino-diterpenoid alkaloids (ADAs), 2 C20-diterpenoid alkaloids, and seven unclassified alkaloids. The three most abundant alkaloids were structurally identified as pseudoaconitine, 8-deacetylpseudoaconitine, and 3′-methoxyacoforestinine, and were identified as the main causative agents of this poisoning. To our knowledge, this is the first detection of these alkaloids in Aconitum poisoning in China. These findings demonstrate that integrated targeted and untargeted toxicological analysis can identify undocumented toxins in poisoning events of unknown origin and clarify the chemical etiology of unusual Aconitum poisoning. Full article

Euphorbia clavarioides Boiss. is traditionally used in wound healing and other medicinal applications. Its bioactive compounds and pharmacological potential remain underexplored. This study investigated the phytochemical composition, antioxidant, anti-inflammatory, and anticancer activities of E. clavarioides Boiss. traditionally used in wound healing. Plant extracts were characterized using phytochemical screening, Fourier-transform infrared spectroscopy (FTIR), and liquid chromatography–mass spectrometry (LC-MS). Antioxidant activity was evaluated via DPPH and nitric oxide (NO) scavenging assays, anti-inflammatory effects through nitrite inhibition in LPS-stimulated RAW 264.7 macrophages, and anticancer potential using the MTT assay against DU-145, PC-3, SKU-T, and AGS cell lines. Phytochemical screening confirmed tannins, phlobatannins, saponins, flavonoids, alkaloids, steroids, terpenoids, and cardiac glycosides. FTIR spectra of aqueous extracts revealed peaks at 2990.66 cm⁻¹ (O–H), 1738.68 cm⁻¹ (C=O), 1217.22 cm⁻¹ (C–N), and 527.37 cm⁻¹ (C–Cl). LC-MS profiling identified diverse metabolites, including phenolics (pseudolaroside B, cinnamtannin A2, (−)-medicarpin, butyrolactol A) and terpenoids (zerumbone, sclareol isomer, diterpenoid-like compounds), underpinning the plant’s bioactivity. Methanol extracts exhibited the strongest DPPH scavenging activity (IC₅₀ = 755.71 µg/mL), whereas aqueous and ethanol extracts demonstrated superior NO scavenging. Ethanol extracts showed maximal anti-inflammatory activity, while aqueous extracts induced pro-inflammatory effects. Cytotoxicity assays indicated negligible toxicity. In anticancer assays, ethanol and methanol extracts significantly inhibited the proliferation of all tested cell lines at 100 µg/mL, exceeding drug control, whereas aqueous extracts displayed lower activity. The bioactive compounds in E. clavarioides support its traditional wound-healing use and demonstrate mechanistic antioxidant, anti-inflammatory, and anticancer activities, highlighting its potential as a source of multi-target natural therapeutics. Full article

This review provides a comprehensive overview of the modulatory actions of plant-derived constituents on membrane ion channels in various cell types. Among their diverse bioactivities, ion channel regulation—governing membrane excitability, signal transduction, and cellular homeostasis—has emerged as a critical mechanistic basis for their pharmacological effects. Twenty-four representative phytoconstituents are discussed and classified into five major categories based on their structural features: alkaloids, terpenoids, lignans and acetogenins, polyphenols, and other aromatic and conjugated compounds. Across these categories, the reviewed compounds exhibit distinct and often highly specific effects on the amplitude and gating kinetics of multiple ionic currents, including voltage-gated Na⁺ currents (I_Na), delayed-rectifier K⁺ currents (I_K(DR)), M-type K⁺ currents (I_K(M)), hyperpolarization-activated cation currents (I_h), erg-mediated K⁺ currents (I_K(erg)), inwardly rectifying K⁺ currents, and Ca²⁺-activated K⁺ currents (I_K(Ca)). Alkaloids predominantly suppress voltage-gated K⁺ currents, with notable exceptions such as aconitine, which alters the properties of both I_Na and I_K(DR), thereby contributing to its proarrhythmic toxicity. Terpenoids, including cannabidiol, croton diterpenoids, lutein, thymol, and triptolide, exert multifaceted effects on I_K(M), I_h, inwardly rectifying K⁺ currents, and Ca²⁺-activated K⁺ channels. Lignans and acetogenins, such as gomisin A, honokiol, sesamin, and squamocin, primarily modulate I_Na, I_h, and I_K(Ca), with several compounds demonstrating strong links between ion-channel modulation and anti-neoplastic or neuroprotective actions. Polyphenolic compounds, including curcumin, eugenol, resveratrol, gastrodigenin, gastrodin, and pterostilbene, display diverse ion-channel targeting profiles, influencing multiple Na⁺ and K⁺ channel subtypes. Other aromatic or conjugated compounds, such as isoplumbagin, plumbagin, and verteporfin, regulate I_K(erg) and I_K(Ca), potentially contributing to both therapeutic efficacy and adverse effects. Collectively, the compound-specific modulation of current amplitude and gating kinetics offers valuable mechanistic insight into the pharmacological and toxicological significance of plant-derived natural products, highlighting the functional role of ion channel evaluation in guiding their therapeutic development and ensuring safety assessment. Full article

Background: Huafeng Dan (HFD) is a traditional famous medicine from Guizhou Province, commonly used for the treatment of stroke-induced hemiplegia and epilepsy. Yaomu is a key component and serves as the sovereign herb in the formula. Most of the components of Yaomu are toxic Chinese herbal medicines. Traditional fermentation processing methods are required to reduce its toxicity. Purpose: Current studies have not yet systematically analyzed the chemical constituents before and after fermentation. Meanwhile, there is a lack of safety evaluation before and after the fermentation of Yaomu, which can provide a basis for safe clinical medication. Method: Chemical constituents of Yaomu before and after processing were analyzed using UHPLC-Q/TOF-MS to compare compositional changes induced by fermentation. To further screen potential toxic components, representative compounds were selected from these differential compounds based on statistical indicators (such as VIP value), low cost and easy availability, as well as criteria from the literature, and the content changes before and after fermentation were investigated. In vitro toxicity was evaluated using a microfluidic liver organ-on-a-chip model to assess the toxic effects of Yaomu extracts before and after fermentation. Results: Studies have shown that in both positive and negative ionization modes, a total of 361 compounds were annotated in unfermented Yaomu. After fermentation, a total of 350 compounds were annotated. Multivariate statistical analysis revealed significant differences in the chemical composition of Yaomu before and after fermentation. Quantitative analysis demonstrated that the levels of diester-type diterpenoid alkaloids were significantly reduced after fermentation, accompanied by concurrent decreases in lysophosphatidylcholine (LPC) species, compared with unfermented Yaomu. In contrast, the concentrations of amino alcohol-type diterpenoid alkaloids were significantly increased. The microfluidic liver organ-on-a-chip results demonstrated that the post-fermentation extract caused significantly attenuated impairment of hepatocellular function and viability. The in vitro toxicity findings showed good concordance. Full article

Bowdichia virgilioides Kunth is a tree largely present in South America, notably in the Cerrado savannah. The species is known for the quality of its dense and resistant wood, used in construction and furnishing. B. virgilioides is also a medicinal plant used, from leaves to roots, for the treatment of various human pathologies (pharyngitis, bronchitis, healing wounds, diabetes, and arthritis). The present review provides an analysis of the scientific literature pertaining to B. virgilioides, with a focus on pharmacological activities. Aqueous and organic extracts have been used to treat inflammatory pathologies and to combat infectious diseases caused by microorganisms and parasites. All phytochemicals at the origin of the bioactivities of extracts have been identified, including 37 terpenoids, 8 alkaloids, 21 flavonoids and 13 other products. All natural products are discussed, with a focus on a dozen compounds with well-documented pharmacological properties and/or a known mechanism of action. Key products include ormosanine (alkaloid), vouacapane (diterpenoid), lupeol (terpenoid), isoquercetin (flavonoid), isocordoin (chalcone), and little-known specific products (bowdichine and bowdenol). The botanical and phytochemical analysis shed light on this valuable Fabaceae species with the objective to promote its preservation and cultivation, as well as further pharmacological investigations aimed at rationalizing its long-established ethnobotanical use. Full article

Although the diterpenoid alkaloids of Aconitum carmichaelii Debx. have long been a research focus in phytochemistry and pharmacology, systematic studies on the growth and development of its daughter roots remain limited, yet this process critically determines the yield and quality of the medicinal material. This study utilized the Jiangyou-derived daughter root of A. carmichaelii as experimental material. Quantitative real-time polymerase chain reaction (qRT-PCR) and total lignin quantification demonstrated that both the expression level of AcPRX12 and total lignin relative content were consistently higher in the non-swollen (PB) parts than in the swollen (P) parts of the daughter roots. The complete cDNA sequence of the AcPRX12 (with a full length of 1357 bp and encoding 350 amino acids) was obtained by rapid amplification of cDNA ends (RACE). Bioinformatics analysis identified AcPRX12 as an extracellular class III peroxidase containing a secretory peroxidase domain, and further predicted its strong binding affinity for syringaldazine, an S-type lignin monomer analog. In addition, the heterologous expression of AcPRX12 in Arabidopsis thaliana resulted in a significant increase in lignin content, which inhibited plant growth, as evidenced by shorter roots, thinner stems, smaller leaves, and shorter siliques. Collectively, these results support a model in which AcPRX12 promotes lignin biosynthesis to modulate daughter root development, ultimately shaping its distinctive tapered morphology. In conclusion, our findings propose a lignin-mediated regulatory mechanism for daughter root development controlled by AcPRX12, offering a key gene resource and a theoretical basis for understanding its morphogenesis. Full article

The Croton genus includes a diverse group of plants with remarkable potential in natural products research, particularly due to their bioactive compounds with hypoglycemic and phytochemical significance. This study examines Croton guatemalensis Lotsy, focusing on its chemical composition and its biological efficacy as a glucose-6-phosphatase inhibitor. Phytochemical analysis led to the isolation and structural elucidation of eleven compounds (1–11), including three new ent−clerodane diterpenes, designated crotoguatenoic acids C (9), D (10), and E (11). The absolute configurations of compounds 9–11 were determined by electronic circular dichroism (ECD) as (5R,8R,9R,10S)-configured ent–clerodanes. High-performance liquid chromatography–mass spectrometry (HPLC–MS/MS) revealed 25 peaks tentatively assigned to terpenoids, flavonoids, and alkaloids, highlighting the species’ chemical diversity. In vitro assays using ethanol–water extract (EWE) and isolated compounds with rat liver microsomes demonstrated inhibitory activity against glucose-6-phosphatase (G6Pase), particularly among ent–clerodane diterpenes (73–96%), with EWE and compounds 1, 4, and 11 showing the highest inhibition. Molecular docking analysis revealed strong interactions between these diterpenoids and the G6PC1 binding pocket, with binding energies comparable to chlorogenic acid (positive control). These findings position C. guatemalensis as a valuable source of bioactive diterpenoids and support the potential of ent-clerodane derivatives as natural G6Pase inhibitors for hyperglycemia management. Full article

Aconitum pendulum Busch (Tiebangchui), a traditional Chinese medicinal herb, is recognized for its diverse pharmacological properties and for its significant toxicity. The Zanba stir-frying processing method is commonly employed to mitigate toxicity and enhance efficacy; however, the underlying chemical principles remain insufficiently studied. In order to address this issue, a phytochemical investigation was conducted on the diterpenoid alkaloids present in Zanba-processed Tiebangchui. Eleven diterpenoid alkaloids were isolated by means of chromatographic techniques, including silica gel column chromatography. Their structures were elucidated by extensive spectroscopic analysis (single-crystal X-ray diffraction, IR, HR-ESI-MS) and comparison with literature data. The compounds were identified as 12-epi-turpelline (1), 12-epi-napelline (2), 12-acetyl-napelline (3), azitine (4), flavaconitine (5), nagarutine C (6), nagarutine D (7), 16-epi-pyroaconine (8), spicatine B (9), 3-deoxyaconitine (10), and napelline (11). Notably, compound 1 was characterized as a novel alkaloid. Additionally, compounds 3–9 were isolated from this processed material for the first time. These findings provide crucial chemical insights into the detoxification mechanism of Zanba processing. Subsequent pharmacological evaluation revealed that compounds 10 and 11 exhibit notable anti-inflammatory activities. Moreover, given the structural analogy between the novel alkaloid 1 and the active compound 11, compound 1 is proposed as a promising lead for future structure–activity relationship studies and semi-synthetic modification. Full article

Herb-induced liver injury (HILI) is an increasingly recognized cause of liver damage, associated with the widespread global use of herbal products. Despite its rising incidence, HILI remains underrecognized and underreported due to the absence of specific biomarkers, limited regulatory oversight, and the complexity of multi-ingredient formulations. Diagnostic efforts rely heavily on the Roussel Uclaf Causality Assessment Method (RUCAM), with clinical presentations often nonspecific and dominated by hepatocellular patterns of injury. Epidemiological data demonstrate regional variation, with notably higher case numbers in Asia and the Americas. Mechanistically, HILI may result from either intrinsic (predictable, dose-dependent) or idiosyncratic (unpredictable, immune-mediated) reactions. Genetic predispositions, including certain HLA alleles, have been identified as risk factors. Hepatotoxicity is often linked to specific phytochemicals such as pyrrolizidine alkaloids, catechins, anthraquinones, and diterpenoids, which may contribute to oxidative stress, mitochondrial damage, or immune activation. Additionally, product inconsistencies and contamination complicate risk assessment and safety evaluation. Current management focuses on immediate discontinuation of the suspected product and supportive care, though severe cases may require liver transplantation. Future directions include the development of specific diagnostic tools, implementation of globally harmonized regulatory standards, improved pharmacovigilance systems, and enhanced public and professional education. Addressing these priorities is crucial for reducing HILI-related morbidity while supporting the safe use of herbal therapies. Full article

Mythimna separata (Walker) (Lepidoptera: Noctuidae) is a major migratory pest causing severe damage to cereal crops such as maize, wheat, and rice across Asia, and is also found in many parts of Oceania. With increasing insecticide resistance, botanical alternatives are urgently needed. This study evaluated the insecticidal potential of hypaconitine, a C19-diterpenoid alkaloid from Aconitum coreanum, against M. separata larvae. Hypaconitine exhibited significant stomach toxicity and strong antifeedant activity. It also caused pronounced growth inhibition, prolonged larval and pupal development, reduced pupation and adult emergence, induced morphological deformities, and significantly shortened adult longevity. Crucially, biochemical assays revealed sustained, time- and concentration-dependent upregulation of key detoxification enzymes—carboxylesterase (CarE), glutathione S-transferase (GST), and cytochrome P450 (CYP450)—over 72 h, indicating that hypaconitine imposes severe metabolic fitness costs rather than being readily detoxified. These effects collectively demonstrate that hypaconitine’s insecticidal efficacy arises not only from direct toxicity but also from exploiting the physiological trade-offs inherent in xenobiotic defense. Its multi-modal action—combining larvicidal, antifeedant, growth-regulatory, and metabolism-disrupting effects—presents a novel strategy for bioinsecticide development with a lower risk of resistance evolution. These findings highlight hypaconitine as a promising candidate for sustainable, integrated management of M. separata and other resistant lepidopteran pests. Full article

Diterpenoid diester alkaloids (DDAs) are the primary toxic constituents in aconite herbs, while also being the key pharmacologically active components. Consequently, establishing rapid enrichment and highly sensitive analytical methods for DDAs is of critical importance. Herein, we developed and constructed a gas–liquid microextraction (GLME) device, which enables the rapid and selective enrichment of DDAs from complex matrices. The enriched extract can be directly analyzed by high-resolution Orbitrap mass spectrometry without requiring any further pretreatment. A comparative analysis of six commonly used Aconitum herbs medicines and their processed derivatives was conducted. Notably, GLME enhanced the mass spectrometric signals of DDAs by 3–4 orders of magnitude, facilitating the identification of 27 alkaloids, including 3 potential new compounds (15-Ethyl-13-deoxyanhydroaconitine, 13-Hydroxy-15-ethylanhydroaconitine and 8-eicosapentaenoic-benzoylmesaconine). It was found that among the tested samples, the DDAs response intensity of raw Caowu was the highest, and the DDA signals decreased significantly after processing. This result chemically validates the detoxification efficacy of traditional methods. The proposed GLME-MS strategy has the advantages of being green, economical, easy to operate, and highly selective (>1000-fold), which provides a technical reference for the rapid detection, safety assessment, and quality control of Aconitum herbs. Full article

As the global population grows, food security and agricultural productivity face challenges, and insect pests cause significant losses to crops. The effectiveness of traditional chemical pesticides is declining, and eco-friendly pesticides need to be developed. Diterpenoid alkaloids (DAs), natural products of plant origin, have attracted attention due to their low environmental risks. Here we review the classification, structure, insecticidal and anti-feeding activities of diterpenoid alkaloids, as well as the current state of research on these chemicals. Studies have shown that C₁₉- and C₂₀-diterpenoid alkaloids show significant activity against a variety of insects, but there are still limited studies on C₁₈-diterpenoid alkaloids. Therefore, through in-depth research on diterpenoid alkaloids, we have discovered that there are various compounds with high efficiency and specificity in insecticidal and antifeedant activities among C₁₉- and C₂₀-diterpenoid alkaloids, which exhibit high selectivity and efficiency towards target pests. This paper emphasizes the potential of diterpenoid alkaloids as novel biopesticides and highlights the need to combine new technologies to conduct further systematic evaluation and screening of these compounds. This work provides new ideas for the development of environmentally friendly pesticides and contributes to sustainable agricultural practices. Full article