Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder characterized by abnormal proliferation of fibroblast-like synoviocytes and excessive secretion of pro-inflammatory cytokines. Strychnos nux-vomica L. (S. nux-vomica) is a traditional medicinal herb used for treating arthritic disorders, while the material basis for its anti-RA activity remains poorly understood. In the present study, twenty-three monoterpene indole alkaloids (MIAs), including eight undescribed compounds (1-8) and fifteen known analogues (9-23), were isolated from the seeds of S. nux-vomica. All isolates were screened for their anti-proliferative activities on TNF-α-induced human RA fibroblast-like synoviocyte MH7A cells. Fourteen MIAs showed inhibitory effects with IC50 values ranging from 9.2 to 48.3 μM. Among them, protostrychnine A (8) exhibited the most potent effect with an IC50 of 9.2 μM. Further mechanistic studies revealed that compound 8 significantly suppressed MH7A cell proliferation and inhibited the NF-κB signaling pathway. These findings enrich the structural diversity of MIAs from S. nux-vomica, and provide a promising lead compound for the development of anti-RA agents.

In India and other countries, large and ancient trees that persist in sacred groves and human-dominated landscapes support ecosystem services, including frugivore-mediated seed dispersal. In this study, we assessed the ecological significance of 'giant' trees (>1 m trunk circumference) in Vanzole Village, Western Ghats, India. We documented 82 giant trees belonging to 20 species in four sacred groves and surrounding human settlements. Sacred groves harbored a higher species richness of large trees (14 species, N = 44) than human settlements (8 species, N = 38). Tree composition varied, with Mangifera indica (Mango) and Artocarpus heterophyllus (Jackfruit) dominating in human settlements, whereas Terminalia bellirica (Beheda) and several other species were more abundant in sacred groves. Giant trees in human settlements exhibited larger canopy diameter (p = 0.002) and DBH (p < 0.001), while trees in sacred groves were significantly taller (p < 0.001). Sapling recruitment was notably higher in sacred groves; Caryota urens saplings were found under 91% of trees in groves (mean = 56.0) versus 47% in settlements (mean = 4.9). The larger-seeded Strychnos nux-vomica was nearly absent in human settlements (5%) compared to sacred groves (77%). Our study highlights the unique conservation value of sacred groves due to their retention of numerous and diverse giant trees. Together with remnant large trees in human settlements, this network is vital for sustaining the regeneration of zoochorous species by supporting the activity of hornbills and other frugivores.

Strychnos nux-vomica L. seeds (SNV) are a rich source of bioactive compounds with antioxidant and antidiabetic properties. In this study, the deep eutectic solvent-ultrasound assisted extraction (DES-UAE) is applied for the extraction of bioactive compounds from SNV seeds, which significantly enhances extraction efficiency, while reducing environmental impact. DES made up of ammonium acetate-propanoic acid (1:3) in combination with ethanol and UAE offered higher recovery rates of SNV bioactive. The extraction process was optimized using response surface methodology (RSM) along with artificial neural networking (ANN), considering extraction time (X1), temperature (X2), and DES/feed ratio (X3) as the independent variables. The dependent variables (responses) evaluated were extraction yield, the total phenolic and flavonoid (TP and TF) content, antioxidant capacity (AC), and antidiabetic (AD) potential. Optimal extraction conditions (25 min, 40 °C temperature, 30 mL/g DES/feed ratio) at 40 kHz ultrasound frequency resulted in 6.31% yield, 64.72 (mg GAE/g) dw TP, 103.19 mg (QE/g) dw TF, 89.87% AC, and 68.53% antidiabetic (AD) potential. The model’s reliability was confirmed through smaller (≤ 5%) relative standard deviation (RSD), root mean square error (RMSE), percentage prediction error (PPE), absolute average deviation (AAD), and R² values. Scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) analysis showed effective cell disruption, supporting enhanced extraction. The outcomes of the present research recommend that DES-based solvent in combination with UAE can be further explored for sustainable and efficient extraction of phenolic bioactives.

In homeopathic prescribing, emotional and mental traits play a key role in remedy selection. The rubric "sympathetic", commonly found in homeopathic repertories, represents traits such as empathy, sensitivity and compassion. However, its inclusion of particular medicines raises concerns regarding discriminative validity. This study applied a likelihood ratio (LR)-based statistical method to evaluate the strength of association between medicines and the rubric "sympathetic", aiming to enhance scientific reliability and evidence-informed prescribing.An 18-month analytical, longitudinal, epidemiological study was conducted at the outpatient departments of a homeopathic hospital in India. Participants aged ≥12 years with chronic illnesses were included, classified as "sympathetic" based on the validated Modified Trait Sympathy Scale - Homeopathic Perspective (mTSS-HP). Individualized homeopathic treatment was provided in centesimal or LM potencies. Treatment outcome was assessed using the Outcome Related to Impact on Daily Living (ORIDL) scale over a 3-month follow-up. Likelihood ratios (LR(+) and LR(-)) were computed from 2 × 2 contingency tables to quantify associations between medicines and the rubric "sympathetic".A total of 1,372 participants were enrolled; 1,327 (96.7%) completed the study. The cohort was predominantly female (74.2%) and had a mean age of 38.9 ± 13.7 years. Among 78 prescribed medicines, Ignatia amara (LR(+) = 2.0), Carcinosinum (LR(+) = 2.2), Staphysagria macrosperma (LR(+) = 1.9), and Nitricum acidum (LR(+) = 2.6) showed strong positive LRs, suggesting a significant association with the "sympathetic" rubric. Remedies such as Bryonia alba, Nux vomica, Natrum sulphuricum, and Sulphur demonstrated LR(+) <1, indicating weaker associations.LR-based analysis identified a restricted set of medicines with robust statistical association with the rubric "sympathetic", supporting the need for selective refinement of repertorial listings. This approach strengthens the empirical foundation of mental-emotional rubrics and offers a reproducible framework for evidence-informed, individualized homeopathic prescribing.

Strychnine has been used for hundreds of years as a medicinal remedy for a broad range of ailments. Although it has now become a rare poisoning agent, sporadic ingestions still occur throughout the United States. Strychnine inhibits postsynaptic glycine receptors predominantly in the spinal cord, causing involuntary painful skeletal muscle contractions. Patients present with “awake seizures" which are episodic muscle contractions with no post-ictal period and normal mental status. Treatment is mainly supportive with benzodiazepines and management of complications from excessive muscle contraction. Most patients who survive acute poisoning do not have chronic sequelae of the poisoning.

This study investigated the toxicological mechanisms of different processed products of Strychnos nux-vomica seeds using serum metabolomics analysis. Seventy-two female KM mice were randomly divided into six groups(n=12 per group): control, raw seeds, vinegar-processed seeds, urine-soaked seeds, sand-roasted seeds, and oil-fried seeds. Each processed preparation group received an aqueous decoction of the original herb at the same concentration for 7 days. Hepatic and renal coefficients were measured in each group, and the levels of hepatic and renal injury markers, including aspartate transaminase(AST), alanine transaminase(ALT), blood urea nitrogen(BUN), and creatinine(CRE) were determined using a fully automated biochemical analyzer. Hematoxylin-eosin(HE) staining was used for histopathological examination of the liver and kidney. Liquid chromatography-mass spectrometry(LC-MS/MS) combined with multivariate statistical analysis was employed to screen for differential serum metabolites across groups. Metabolic pathway enrichment analysis of the selected differential markers was performed using the Human Metabolome Database(HMDB) and MetaboAnalyst 6.0. All processed S. nux-vomica seed products increased hepatic and renal coefficients and elevated hepatic and renal injury markers(AST, ALT, BUN, CRE), although these effects were reduced to varying degrees compared to the raw product. Overall, vinegar processing exhibited the most significant detoxification effect, followed by oil-fried&gt;sand-roasted≈urine-soaked&gt;raw seeds. Metabolomic analysis identified 14 differential metabolites across the groups, primarily including sphingolipids, glycerophospholipids, and vitamin-related compounds. Five significantly perturbed metabolic pathways were identified: sphingolipid metabolism, glycerophospholipid metabolism, α-linolenic acid metabolism, lipoic acid metabolism, and linoleic acid metabolism, with sphingolipid and glycerophospholipid metabolism common to all groups. In conclusion, processing of S. nux-vomica seeds reduced hepatorenal toxicity to varying degrees, and its toxic mechanisms may primarily involve disturbances in sphingolipid and glycerophospholipid metabolism.

Homeopathic medicines from plant sources such as Nux vomica face skepticism due to presumed absence of original material in high potencies (30cH, 200cH) whose dilution exceeds Avogadro's number. Whilst nanoparticles exist in metal-derived preparations, physicochemical characterization of plant-based remedies remains limited.This study aimed to analyze Nux vomica potencies (Q to 200cH) to determine nanoparticle presence, stability and retained molecular signatures.We characterized Nux vomica potencies using dynamic light scattering (DLS) for particle size distribution, electrophoretic light scattering for zeta potential, UV-vis spectroscopy for electronic absorbance profiles, and Fourier transform infrared (FTIR) spectroscopy for functional group analysis. Measurements were compared with ethanol control.DLS revealed bimodal particle distribution in nanometer (140-697 nm) and micrometer (0.8-2.5 µm) ranges across potencies, indicating complex colloidal structures. Zeta potential confirmed stable, negatively charged suspensions, with a negative charge spike at 60cH (-16.85 mV), suggesting stable nanoaggregates. UV-vis spectroscopy showed peaks at 261 nm (strychnine) and 331 nm (brucine), with a broad band between 920 and 1,025 nm. A hypsochromic shift occurred with increasing potencies. Higher potencies showed shifts toward shorter wavelengths, changes in peak intensities, and altered absorption patterns, suggesting solvent-related structural modulation. FTIR spectra showed absorption bands for OH, C-H, N-H, C = O, C-N and C-O stretching vibrations, representing sample constituents.This study provides evidence that high-potency Nux vomica preparations contain stable nanostructures and retain molecular signatures of source material. The non-linear changes in particle size, surface charge and molecular architecture suggest that succussion induces dynamic cyclical transformations in the colloidal system.

Wound healing is a vital biological process that restores damaged tissue. In diabetes, this process slows down due to chronic inflammation and oxidative stress. Brucine, a natural compound from Nux vomica, is known for its anti-inflammatory and antioxidant actions and its ability to promote fibroblast growth. However, its poor solubility and toxicity limit its clinical use. To address these issues, a nanoemulgel formulation was developed to improve the delivery and wound-healing effectiveness of brucine. The study aimed to develop and evaluate a brucine-loaded nanoemulgel for wound healing. The objectives were to (i) study molecular interactions of brucine with wound-healing proteins using in-silico analysis, (ii) prepare and characterize the nanoemulgel, and (iii) test its wound-healing ability in diabetic rats. Molecular docking was performed using AutoDock 4.1 to predict brucine's binding with proteins involved in fibroblast proliferation and tissue repair. The nanoemulgel was prepared by incorporating brucine-loaded nanoemulsion into a hydrogel base. Its drug release, skin permeation, and stability were tested using standard laboratory techniques. Wound healing was evaluated in streptozotocin-induced diabetic rats by measuring wound closure over 14 days and analyzing tissue samples microscopically. Docking results showed strong binding of brucine with fibroblast growth factor receptor (FGFR, - 9.63 kcal/mol) and epidermal growth factor receptor (EGFR, - 9.17 kcal/mol), indicating its potential to stimulate cell growth and repair. The nanoemulgel showed 1.8-fold higher drug permeation and controlled release up to 12 h compared to plain gel. In diabetic rats, wounds treated with brucine nanoemulgel showed 80% closure by day 14, compared to 65% with standard treatment and 40% in untreated controls. Histopathology confirmed better collagen formation, fibroblast proliferation, and reduced inflammation. The brucine-loaded nanoemulgel improved drug delivery and significantly accelerated diabetic wound healing. It enhanced fibroblast activity and tissue repair while minimizing inflammation. This nanoformulation offers a promising topical strategy for chronic wound management, warranting further stability and clinical studies.

Dengue is an acute mosquito-borne viral infection that has become a major health problem worldwide in recent years. Currently, no specific antiviral therapies are available to treat dengue fever. Every year, an enormous number of deaths are reported due to dengue fever. This necessitates the identification of inhibitors against the dengue virus. The RNA genome of DENV is composed of 10,723 nucleotides, which encodes for 10 proteins (three structural proteins and seven nonstructural proteins). The nonstructural NS2B-NS3 protease complex has been reported to be the most powerful therapeutic target for the development of anti-dengue drugs. In the present study, a ligand library comprised of 3496 phytochemicals from 160 medicinal plants was subjected to high-throughput virtual screening against the NS2B-NS3 protease of dengue virus. The top 25 best-fit compounds were shortlisted based on their binding affinity, RMSD UB, and LB values. The binding energies of these phytochemicals were found to be within the range of -9.84 to -2.98 kcal/mol. These phytochemicals were further analyzed through site-specific docking for 100 independent genetic algorithm (GA) runs. With further analysis of hydrogen bond interactions, binding energy, and clustering, the best binding confirmations of the four protein-ligand complexes were identified. It includes 4-hydroxystrychnine (Strychnos nux-vomica, PubChem ID: 211181), andrograpanin (Andrographis paniculata, PubChem ID: 11666871), norsanguinarine (Argemone mexicana, PubChem ID: 97679), and pongaglabrone (Pongamia pinnata, PubChem ID: 10957726). The thermodynamic stability of these protein-ligand complex structures was evaluated using Schrödinger's Desmond (v7.3) molecular dynamics simulation for a duration of 100 ns. These complex structures were identified to be stable throughout 100 ns. With further experimental and clinical investigations, potential inhibitors identified in the present study could be used as effective lead molecules for the development of novel drugs against the dengue virus.

Brucine (BRU), a naturally occurring indole alkaloid primarily derived from Strychnos nux-vomica, has recently gained attention for its notable anticancer potential. Preclinical studies using both in vitro and in vivo models have demonstrated that BRU and its semi-synthetic derivatives exhibit significant inhibitory effects on tumor development across various cancer types, including cervical, breast, liver, skin, colon, and prostate cancers. This review explores the phytochemical properties of BRU, its chemical modifications, bioavailability, pharmacokinetics, mechanisms of anticancer activity, as well as findings from clinical research, toxicity profiles, and safety evaluations. Compared to conventional chemotherapeutic agents, BRU offers a promising alternative due to its broad-spectrum efficacy and natural origin, although its therapeutic application is limited by a narrow safety margin. Therefore, future research should focus on the development of optimized semi-synthetic derivatives and advanced drug delivery systems to enhance its pharmacological performance while minimizing toxicity, supporting its potential as a viable candidate in anticancer therapy.

Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of abnormal plasma cells, with marked heterogeneity and therapeutic refractoriness. Despite the introduction of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies (mAbs), and chimeric antigen receptor T-cell (CAR-T) therapy, relapse and drug resistance remain major challenges that urgently need to be addressed. Plant-derived natural products have attracted increasing attention in recent years due to their multi-target synergistic effects, demonstrating unique potential in inducing MM cell apoptosis, reversing drug resistance, and modulating the immune microenvironment-making them a rising focus in translational medicine research. In this structured narrative review, we systematically summarize the anti-myeloma mechanisms of fourteen plant-derived natural products, including plant-derived monomeric compounds (baicalein, artemisinin, curcumin, celastrol, gambogic acid, resveratrol, ginsenosides, icariin, oridonin, plumbagin, formononetin) and standardized plant extracts (Strychnos nux-vomica root extract, dandelion flavonoids, Hedyotis diffusa polysaccharides). This review highlights their multi-target regulatory effects on signaling pathways, cell cycle modulation, and immune regulation, and further discusses their potential translational value in overcoming drug resistance and optimizing combination treatment strategies. Literature was retrieved from PubMed, Web of Science, and CNKI databases, covering studies published up to January 2025. Although plant-derived natural products exhibit promising multi-target regulatory mechanisms in MM therapy, their clinical translation remains limited by poor bioavailability of single compounds and the lack of standardized extracts. Future research should integrate systems pharmacology with clinical studies to elucidate multi-component synergistic networks and develop novel targeted formulations, thereby accelerating the efficient translation of phytochemicals from bench to bedside.

Gastric cancer (GC) is the third leading cause of cancer mortality globally, often presenting with insidious symptoms that lead to late-stage diagnoses, underscoring the critical need for innovative diagnostic and therapeutic strategies. One such avenue is the exploration of ferroptosis, a regulated form of cell death implicated in various pathological conditions and malignancies. In this study, we demonstrate that brucine, an alkaloid derived from Strychnos nux-vomica, exerts significant antitumor effects on GC cells both in vitro and in vivo. Brucine treatment dose-dependently inhibits proliferation, migration, and invasion, and induces apoptosis and ferroptosis. Specifically, brucine treatment diminished cell viability, DNA synthesis, and colony formation, increased the expression of proapoptotic markers such as Bax, and decreased the expression of antiapoptotic Bcl-2. Additionally, brucine inhibited migration and invasion by modulating epithelial-mesenchymal transition markers. In ferroptosis assays, brucine potentiated the effects of the ferroptosis inducer Erastin, elevating levels of intracellular iron, malondialdehyde, and reactive oxygen species, while reducing glutathione levels. In vivo experiments showed that brucine markedly reduced tumor growth and modified the expression of key biomarkers in a xenograft model. Furthermore, our findings suggest that brucine's effects on cancer cell behavior and ferroptosis are associated with suppression of the NF-κB signaling pathway, suggesting an indirect modulation of this pathway. In conclusion, this study elucidates the comprehensive antitumor properties of brucine against GC, highlighting its ability to inhibit cellular proliferation, migration, and invasion, while promoting apoptotic and ferroptotic pathways. These effects are potentially mediated through indirect modulation of the NF-κB signaling pathway.

Four undescribed cytochalasins and ten known cytochalasins were isolated from the culture of Diaporthe hongkongensis, an endophytic fungus obtained from the leaves of Strychnos nux-vomica. Notably, diacytochalasin A (1) was the first cytochalasin discovered that features a unique 5/5/11 fused tricyclic ring system. The structures and absolute configurations of the four compounds were elucidated by performing comprehensive spectroscopic analyses and by examining their experimental and calculated electronic circular dichroism (ECD) spectra. These cytotoxic activities of 1-14 against five cancer cell lines, HGC-27, HCT-116, U87, MCF-7, and HepG2, were evaluated in vitro. Compounds 1, 3, 7, 9, 13, and 14 exhibited notable cytotoxicity to HGC-27 tumor cells with IC50 values in the range of 0.1-3.59 μM.