Abstract:

Activation of microglia and resulting neuroinflammation are central processes that significantly contribute to neurodegenerative disease progression. Treatments capable of attenuating neuroinflammation are therefore an urgent medical need. Vitis vinifera L., cultivated since ancient times for its fruits, is known for its antioxidant and anti-inflammatory activities. However, polyphenols, the main bioactive molecules in V. vinifera extracts, vary considerably due to numerous hard-to-control factors, making it difficult to obtain standardized extracts with consistent biological activity. To address this issue, plant cell culture biotechnology was used to produce a highly standardized V. vinifera phytocomplex (VP), and its anti-neuroinflammatory profile was investigated in LPS-stimulated microglial cells, an in vitro model of neuroinflammation. VP reduced the LPS-induced pro-inflammatory phenotype, improved cell viability and cell number, attenuated NF-κB activation and ERK1/2 phosphorylation, and increased SIRT1 levels. To overcome VP’s poor water solubility, water-soluble, nanocellulose-based formulations containing cellulose nanocrystal (CNC) were developed and tested. VP-CNC formulations markedly reduced the BV2 pro-inflammatory phenotype and increased cell viability under both basal and LPS-stimulated conditions. The nanoformulations also decreased pERK1/2 levels and increased SIRT1 expression, exhibiting biological activities comparable to VP alone. V. vinifera phytocomplex derived from plant cell cultures represents an innovative and standardized product with promising antineuroinflammatory properties.

Abstract: Background: Cardiovascular diseases, driven by platelet hyperactivation and thrombosis, remain the leading global cause of death. Excessive platelet activation contributes to ath-erosclerosis and thrombo-inflammatory disorders, underscoring the urgent need for safer and more effective antiplatelet agents. Objectives: Xanthium strumarium L. (X. strumarium) has been reported to exhibit a wide range of pharmacological effects, including an-ti-inflammatory and antioxidant activities. However, its antiplatelet and antithrombotic effects remain unexplored. Therefore, the present study aimed to evaluate these effects us-ing integrated in vitro, in vivo, and network pharmacological approaches. Methods: In vitro antiplatelet effects were evaluated via light transmission aggregometry, ATP and cal-cium mobilization assays, αIIbβ3 signaling, and western blot analysis. In vivo ferric chlo-ride-induced (FeCl3) murine thrombus model was established to evaluate thrombogenesis. The major compounds identified by GC-MS analysis were analyzed for pharmacokinetics, drug-likeness, and network pharmacology. Results: Our results demonstrated that X. strumarium at 25, 50, or 100 μg/mL significantly inhibited agonist-induced platelet aggre-gation. The granule secretion, integrin-αIIbβ3 signaling, and the MAPK and PI3K/Akt pathways were also dose-dependently inhibited. The in vivo blood flow rate and the mice survival rates were improved. BOILED-Egg analysis revealed that catechol, 2,1,3-benzothiadiazole, and hydroquinone exhibited high gastrointestinal absorption (score ≥ 0.55), suggesting favorable pharmacokinetic properties. Finally, network phar-macological analysis linked these compounds to platelet- and inflammation-related genes enriched in KEGG pathways, including those related to the Toll-like receptor, HIF-1, and actin cytoskeleton regulation. Conclusions: Collectively, X. strumarium exhibited potent antiplatelet and antithrombotic properties with the identification of catechol, 2,1,3-benzothiadiazole, and hydroquinone as key bioactive compounds.

Abstract: Non-organic (muscle) weakness (NOw) is proposed as a distinct pathological entity characterized by maladaptive neuroplasticity (learning) affecting motor control. Functional deficits are most directly revealed through the manual muscle testing (MMT) break test, which uniquely exposes a muscle’s ability to adapt to increasing external load, potentially serving as an index of motor control integrity. We advance the “muscle-motor-movement PTSD” (mPTSD) model in which learning during pain or stress (trauma) yields chronic avoidance (inhibition) of associated muscles. In a second stage, compensatory synergies develop, overriding attempts at hypertrophy-oriented training. This non-systematic, integrative review synthesizes clinical reports, learning theories, motor control and pain literature, and objective tests of force and movement over time during MMT. Predictive processing and reinforcement learning offer complementary accounts of how hyper-precise priors and passive avoidance may maintain NOw beyond functional recovery. Unexplained muscle weakness is found in non-specific musculoskeletal disorders and functional motor disorder (functional weakness), but may also contribute to other conditions, such as kinesiophobia. Effective alternative treatments for NOw may act by updating or erasing maladaptive motor learning by disrupting memory reconsolidation, allowing immediate restoration of function. Analogous to psychoneuroimmunology’s role in immune function, we propose “psychoneurokinesiology”, the study of how maladaptive learning affects movement.

Abstract: Background/Objectives: Cancer-related fatigue is one of the most distressing symptoms complained by neoplastic patients. L-arginine has a positive effect on physical performance in normal individuals, on fatigue in diseases other than cancer and on immune response in cancer patients. Methods: Forty-four cancer patients undergoing medical treatment were treated with oral l-arginine 1.66 g and 500 mg of vitamin C b.i.d. Cancer-related fatigue and health-related quality of life were recorded before treatment and after 15 and 30 days employing a visual analog scale and the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) respectively. Results: Daily oral supplementation with l-arginine and vitamin C ameliorated cancer-related fatigue in a statistically significant manner. Health-related quality of life remained mostly unchanged despite patients had advanced cancer and were administered medical treatments including chemotherapy, immunotherapy and biologics. No effect on appetite preservation was observed but in a small percentage of patients Conclusions: Our exploratory study suggests a positive effect of oral supplementation with l-arginine plus vitamin C on cancer related fatigue without significant worsening of quality of life. Due to the heterogeneity of patients sample further studies are needed including more clinically homogenous groups of patients.

Abstract: Post-COVID condition - the long-term illness seen after coronavirus infection - often presents with chronic refractory widespread musculoskeletal pain, for which no well-formulated treatment or rehabilitation strategy has so far been established in studies. Integrative medicine aims to optimize treatment outcomes while incorporating a holistic patient centered approach. A valuable yet underused modality available to practitioners since antiquity is the acupuncture practice of needling therapy, whose working mechanism of action remains poorly elucidated and disputed - which is part of the reason why it is often met with skepticism by many medical practitioners. One of the most difficult chronic pain conditions to treat, and for which modern medicine provides symptomatic and insufficient therapies, is the syndrome of fibromyalgia. Fibromyalgia is a prevalent pain condition of unknown etiology that manifests with a peculiar cluster of symptoms such as myalgia/arthralgia, fatigue, low mood, and cognitive difficulties. Its pathophysiology is largely attributed to dysregulated central neural pain pathways, although fascio-musculoskeletal pathology is evident. Recent studies indicate that fibromyalgia-type manifestations occur often after coronavirus infection, in what can be termed “long-covid-19 syndrome”, a condition which also seems to involve myofascial histopathological abnormalities in a significant number of affected individuals. Empirical studies suggest that needing therapy may improve chronic widespread pain and it has been recommended by professional medical societies to be used in fibromyalgia and “neuroplastic pain,” but the biological mechanisms are poorly known and are mainly attributed to central nervous system neurophysiology. In this manuscript a new mechanism of action for manual needling is formulated as a global percutaneous needle fasciotomy that respects tensegrity principles, and is discussed as part of the rehabilitative approach for the treatment of post-covid widespread musculoskeletal pain and stiffness. This approach, complementing known neurophysiological mechanisms, offers a more holistic understanding of acupuncture’s usefulness as a rehabilitative treatment for idiopathic chronic musculoskeletal pain and refractory post-covid myofascial and nociplastic-type pain. Tensegrity-based needling aligns with traditional medical principles of the body-mind as a unit by recognizing the global interconnectedness of the myofascioskeletal system and aiming to restore balance and function.

Abstract: Ethnobiological and ethnomedicinal relevance: The absence of standardized criteria and clear formulation guidelines for animal-derived ingredients in Traditional Chinese Medicine (TCM) dietary therapy restricts their effectiveness in subhealth management.Aim: This study aims to develop a three-dimensional (3D) evaluation-triple-component formulation system to quantify Yin-Yang properties (a core TCM classification describing ingredient thermal characteristics as hot/warm, mild, cool/cold) and standardize compatibility.Materials and Methods: Drawing on Lingnan dietary traditions and more than twenty years of clinical data, a quantification model was constructed, assessing animal-derived ingredients based on their environmental characteristics, metabolic properties, and growth cycles. The efficacy of the standardized formulations was then verified through targeted application according to specific constitutional conditions.Results: Qingyuan chicken demonstrated a significant Yang tendency (+4.2), while deep-sea tuna displayed a Yin tendency (−7.2), aligning with historical records in TCM literature. Clinical application of these formulations in subjects with Yang or Yin deficiencies alleviated symptoms such as cold intolerance and dry mouth, respectively. Animals with Yang tendencies possessed 30%–40% saturated fatty acids, whereas those with Yin tendencies contained 25%–30% omega-3 fatty acids.Conclusions: The proposed system establishes a structured approach for evaluating and formulating animal-derived dietary ingredients. It effectively integrates traditional TCM principles with contemporary ethnobiological and ethnomedicinal practices, enhancing precision and reliability in TCM nutritional therapy.

Abstract:

Ganoderma is a genus of fungi that has been utilized in traditional Eastern medicine and has gained global interest in recent years. Current research has focused on the molecular underpinnings of Ganoderma taxonomy, phylogenetic diversity, and biochemical composition. In this review, we examine the current methods for the molecular identification and classification of the various Ganoderma species, with an emphasis on internal transcribed spacer (ITS) sequencing as well as other molecular barcoding techniques. These methods have improved species delineation, overcoming the limitations traditionally imposed by methods that are morphological in nature. This review also highlights advancements in metabolomics, especially in the identification and quantification of pharmacologically relevant compounds such as triterpenes and polysaccharides. Next, take a closer look at how tools like high-performance liquid chromatography (HPLC) and mass spectrometry (MS) are being used to profile analytes and support quality control efforts. To build a more holistic picture, we draw on insights from systematics, phylogenetics, and metabolomics, bringing together multiple disciplines to propose a more consistent approach for classifying and evaluating the pharmacological potential of Ganoderma. Notably, we highlight regions that have received less research attention, especially parts of Africa, where the full extent of species diversity is still largely unknown.

Abstract: The pathogenesis of knee osteoarthritis (OA) is multifaceted and involves the complete joint microenvironment. Despite beneficial evidence of curcumin, the mechanistic insights of nanoemulsified curcumin (n-Cur) delivery to the knee-OA microenvironment are limited. A detailed histological change that occurs in the knee joint of the OA model after localized delivery of curcumin was examined. n-Cur was prepared using a neutral dietary oil and a surfactant. Adult (5 mo) male SD rats were intra-articularly delivered 40 mg/ml of monoiodoacetate (MIA) to induce OA in the left knee and further treated with n-Cur (30 mg/ml). The effect of n-Cur on macrophage recruitment was evaluated using a co-culture model of CHON 001 and RAW 264.7 cells. In the MIA-model, localized delivery of n-Cur significantly reduced knee-joint edema, and articular cavity stenosis in the target site. Curcumin ameliorated cartilage degeneration by reducing fibrillation, hypocellularity, and restoring matrix proteoglycan, as evidenced by histology. Reduced synovial inflammation displays the effect of curcumin on the synovium, possibly by lowering the recruitment of macrophages in chemoattractant-stimulated chondrocytes. Thus, curcumin nanoemulsion can act as a chondroprotective agent, modulating the OA microenvironment by reducing joint edema, synovial inflammation, and oxidative stress in the OA model.

Abstract: Forest therapy, guided by clinical professionals, is increasingly recognized as a preventive and complementary health practice with evidence-based therapeutic potential; however, the specific contribution of therapist guidance compared to self-guided immersion remains unclear. This retrospective study evaluated the short-term mental health outcomes of therapist-guided (TG) compared to self-guided (SG) forest immersion, based on the validated State–Trait Anxiety Inventory and Profile of Mood States questionnaires. Data were collected from 282 adults participating in eight paired TG–SG sessions conducted at the same forest sites across Italy. Results showed that TG sessions led to greater improvements in state anxiety, self-esteem, and total mood disturbance, with statistically significant effects in most cases. Therapist-led guidance also occasionally reduced interindividual variability, suggesting enhanced emotional regulation. A preliminary economic assessment, based on standardized psychometric improvements translated into quality-adjusted life years (QALYs), indicated that TG sessions yielded approximately 1.7 times higher annual per-person economic value than SG sessions, outweighing the associated therapist-related costs. These findings provide the first large-scale evidence that therapist-guided forest therapy delivers significant and economically quantifiable added value compared to self-guided experiences, supporting its inclusion in preventive health and mental well-being programs and justifying further longitudinal and cost-effectiveness investigations.

Abstract: Chronic inflammation is a central factor in the pathogenesis of obesity, cancer, and type 2 diabetes (T2DM). This article explores an integrated therapeutic strategy, administered via injection, that combines dimethyl sulfoxide (DMSO), coenzyme Q10 (CoQ10), alpha-lipoic acid (ALA), curcumin, Glutathione (GSH), and miR-146a mimetics. Injectable administration optimizes the bioavailability and tissue targeting of these agents, which act synergistically through anti-inflammatory, antioxidant, and metabolic modulating mechanisms. The main focus is on the role of miR-146a in regulating the IRAK1 and TRAF6 signaling pathway, crucial for immunometabolic homeostasis. This multidimensional approach has the potential to modulate chronic inflammation, optimize mitochondrial function, and restore metabolic balance, representing a new frontier in the treatment of chronic inflammatory diseases.

Abstract: The flavonoid quercetin (Q) has recently been suggested as a natural anti-aging and senolytic agent. However, its low stability and poor oral bioavailability limit its benefits and practical application. To address this, a lecithin-based formulation called Quercefit™ Phytosome™ (QF) was developed, which can greatly enhance Q's absorption in humans. This study examines whether QF can improve Q's ability to delay aging and senescence in vivo using the nematode Caenorhabditis elegans. QF provided more effective protection for worms than Q against toxicity caused by thermal and oxidative stress, with effects similar to those of standard antioxidant compounds. Under thermal stress, QF, like Q, increased the worms' lifespan and health span by approximately 50%, counteracting the age-related decline associated with stress. These benefits are supported by QF's capacity to act as a reactive oxygen species scavenger, suppress heat-shock element gene transcription activated by thermal stress, such as hsp-16.2 and hsp-70, and stimulate sod-3 and gst-4 genes involved in antioxidant and detoxification responses. These findings suggest that QF can act at the transcriptional level, protecting against aging and senescence promoted by stressful conditions.

Abstract: Introduction: COVID-19 predominantly affects the respiratory tract, leading to symptoms such as fever, sore throat, cough, and nasal congestion. This study aimed to evaluate the efficacy and safety of nasal spray, mouth spray, and mouthwash containing limonene, cetylpyridinium chloride (CPC), and monolaurin in alleviating symptoms among patients with mild-to-moderate COVID-19. Methods: A double-blind, randomized, placebo-controlled trial was conducted at Dontum Hospital, Thailand, from May to November 2022. A total of 120 RT-PCR–confirmed COVID-19 patients were randomly assigned to receive either the active antiviral formulations or placebo products. Symptom severity was assessed on Days 1, 3, and 7 using a 7-point Likert scale. Patient satisfaction regarding symptom relief and product attributes (color, smell, taste) was evaluated on Day 7 using a 5-point Likert scale. The study was approved by the Ethics Committee of Silpakorn University (COE 65.0517-081) and registered with the Thai Clinical Trials Registry (TCTR20240803002). Results: Compared to the placebo group, the experimental group exhibited significantly faster symptom resolution, particularly for sore throat, cough with mucus, and nasal congestion, with notable improvements observed as early as Day 3 (p < 0.05). By Day 7, a higher proportion of patients in the experimental group reported complete recovery (p < 0.05). Additionally, patient satisfaction scores for symptom relief and product characteristics were significantly higher in the experimental group (p < 0.001). No adverse events were reported in either group. Conclusion: The nasal spray, mouth spray, and mouthwash formulations containing limonene, CPC, and monolaurin were effective and well-tolerated in managing mild-to-moderate COVID-19 symptoms. These findings suggest their potential as adjunctive therapies in outpatient settings. Further large-scale, multicenter studies are warranted to confirm these results and assess long-term clinical benefits. Trial Registration: Thai Clinical Trials Registry (TCTR20240803002).

Abstract: Background: Chronic kidney disease (CKD) remains a major global health burden, driven by oxidative stress, inflammation, and progressive nephron loss. Oxyhydrogen (HHO) nanobubble therapy has emerged as a novel intervention combining molecular hydrogen and oxygen with nanoscale delivery potential. This retrospective observational study evaluated the physiological effects of intravenous HHO nanobubble therapy in patients with CKD. Methods: Data from 47 CKD patients who received intravenous HHO nanobubble therapy as part of routine clinical care were retrospectively analyzed. Baseline and follow-up data were collected from electronic medical records. Estimated glomerular filtration rate (eGFR) served as the primary outcome, with additional analyses on blood pressure, hematological markers, lipid profile, and metabolic parameters. Statistical tests included paired t-tests and Pearson correlation analysis. Results: Following HHO therapy, 61.7% of patients showed improved eGFR, particularly those in CKD Stage III. Significant reductions in systolic (p < 0.001) and diastolic (p = 0.046) blood pressure were observed. Improvements were also noted in lymphocyte count, granulocyte percentage, red cell distribution width (RDW), and total cholesterol (p = 0.04). HDL showed a positive correlation with ΔeGFR (r = 0.54, p = 0.0018), suggesting a potential link between lipid metabolism and renal function. Conclusion: This retrospective study suggests that intravenous HHO nanobubble therapy may support renal function and reduce cardiovascular-metabolic stress in patients with CKD, particularly in moderate stages. These findings warrant further investigation through prospective, controlled studies to confirm efficacy and explore mechanisms.

Abstract: Background: Duchenne Muscular Dystrophy (DMD) is a severe X-linked neuromuscular disorder characterized by progressive muscle weakness due to mutations in the dystrophin gene. Although predominantly affecting males, rare cases have been reported in females. Current standard management with corticosteroids improves function but is limited by significant long-term adverse effects. Therefore, novel complementary therapies with fewer side effects are needed. Case Presentation: We report the case of an 18-year-old female with genetically confirmed DMD presenting with progressive lower limb weakness, difficulty standing, waddling gait, and positive Gower’s sign. The patient underwent 20 sessions of intravenous hydrogen-oxygen nanobubble (NB-HHO) therapy in combination with physiotherapy and nutritional supplementation. After 10 sessions, she demonstrated improved sit-to-stand time (<20 seconds), negative Gower’s sign, and enhanced lower limb muscle strength (from 4/5 to 5/5). Upon completion of 20 sessions, the patient was able to ambulate independently without assistive devices and actively participate in daily and academic activities. Discussion: This case highlights the potential role of NB-HHO therapy in reducing oxidative stress and inflammation—two key mechanisms in DMD progression—while supporting mitochondrial function and oxygen delivery. The observed clinical improvements suggest that NB-HHO may serve as an effective complementary therapy to enhance rehabilitation outcomes in DMD. However, its safety and efficacy require validation in larger clinical trials. Conclusion: Hydrogen-oxygen nanobubble therapy, in combination with conventional rehabilitation, may represent a promising adjunctive approach for female DMD patients. Further research is warranted to establish its therapeutic potential and long-term benefits.

Abstract: Background/Objectives: The purpose of this study was to evaluate the nutrient compo-sition of selected arthropods (insects and crustaceans) and lentil, and to investigate their effects as dietary protein sources on gut microbiota, host metabolism, and associated metabolites. Methods: A total of 63 male Wistar rats were randomly assigned to eight experimental groups and fed diets adjusted to 20% protein from different sources: control (C), cricket (CR), acocil (AC), chinicuil (CHI), beef (B), picanha (P), egg (E), and lentil (L). Diets were administered for 45 days. At the end of the intervention, serum was collected to assess biochemical parameters and microbiota-derived metabolites, liver samples were obtained for histological analysis, and feces were collected for intestinal microbiota pro-filing. Results: Nutritional analysis revealed that L, CR, AC, and CHI contained signif-icantly lower concentrations of choline, carnitine, and phosphatidylcholine—precursors of trimethylamine-N-oxide—than animal-derived sources (E, B, P). CHI was enriched in oleic acid, CR in linolenic acid, and L in linoleic acid, while L also displayed significantly lower cholesterol levels than E. CR, AC, and CHI had the highest chitin contents, followed by L. Consumption of CR or L significantly reduced fat mass, improved glucose sensi-tivity, and lowered hepatic cholesterol and triglycerides compared with E. CHI enhanced hepatic fatty acid β-oxidation. Gut microbiota analysis showed comparable α-diversity after CR, AC, L, and B diets, while high-fat sources (CHI, P, E) reduced diversity. CR increased Faecalibacterium prausnitzii, associated with antioxidant activity, whereas L promoted Bifidobacterium bifidum, inversely related to liver lipids. Both CR and L reduced circulating LPS and glucose AUC. Conclusions: These findings suggest that CR and L represent sustainable and health-promoting protein sources.

Abstract: Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes acute febrile illness characterized by thrombocytopenia and a high mortality rate. Currently, no specific antiviral drugs have been approved for the treatment of SFTSV; therefore, identifying effective drugs against the disease and conducting clinical trials of these drugs are crucial. Drug repurposing is a well-established strategy for utilizing existing licensed drugs for newer indications, facilitating the shortest possible transition from bench to bedside. This approach demonstrated that favipiravir, zaltoprofen, ivermectin, and lurasidone, along with the phytochemicals licoflavone C and oleanolic　acid, are efficacious against the SFTSV. Glycyrrhiza, which contains licoflavone C in its extracts, is a component of the Kampo medicines Kakkon-to, Shosaiko-to and Saiko-keishi-to. Ginseng, which contains oleanolic acid in its extracts, is a component of Shosaiko-to and Saiko-keishi-to. Kampo medicine is a traditional Japanese medicine primarily consisting of organic plant-based ingredients, such as Glycyrrhiza, Ginseng, and others. Multidrug treatment is effective due to the synergistic effects resulting from the various mechanisms of action of the concerned drugs. Therefore, the combination of drugs, such as favipiravir, ivermectin, and Shosaiko-to may be more efficacious against the SFTSV.

Abstract: The investigation of alternatives for the management of breast cancer (BC), has led to the study of extracts of plant origin and their compounds, within these, the extracts of oregano variants and carvacrol (Cv) have shown promising results, however, the Mexican oregano (L. graveolens) infusion (MoI) has not been studied, so the aims of this work are; to characterize the plant used, and to compare against Cv, the impact on the metabolism and cytotoxicity of BC cell lines. Within the characterization of the plant, moisture, ash, protein, available carbohydrates, ethereal extraction and dietary fiber were determined, additionally, for the MoI characterization antioxidant capacity analysis; ABTS, DPPH, phenols, flavonoids and Ferric reducing antioxidant power (FRAP) were carried, as well as Fourier-transform infrared spectroscopy (FTIR) and high performance liquid chromatography (HPLC) to evaluate the composition of the extract, for anticancer activity 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays (MTT) and lactate dehydrogenase (LDH) were performed. The results demonstrated that MoI possesses potent antioxidant activity and antiproliferative effect against BC cell lines, with lower cytotoxicity on non-cancer cells compared to Cv. However, both the infusion and Cv caused a reduction in cell metabolism, with Cv having the most acute effect. Thus, the present investigation provides evidence on the efficacy of these alternative treatments in BC cell lines, including aggressive subtypes such as triple negative (TN).

Abstract: The Crimean-Congo hemorrhagic fever virus is a tick-borne bunyavirus that leads to acute febrile illness with myalgia, dizziness, neck pain and headache and a high mortality rate in humans. Currently, no specific antiviral drugs have been approved for treatment, making the search for effective drugs against this virus and the execution of clinical trials a significant concern. Drug repurposing is a well-established strategy for redeploying existing licensed drugs for newer indications, facilitating the quickest transition from bench to bedside. Computational screening through in silico studies offer a cost-effective and time-efficient approach for identifying potential drug candidates for repurposing. This approach demonstrated that tetracyclines such as doxycycline and minocycline, along with the phytochemical skullcapflavone I, are efficacious against Crimean-Congo hemorrhagic fever virus. Scutellaria, which contains skullcapflavone I in its extracts, is a component of the traditional Japanese medicines Shosaiko-to and Saiko-keishi-to (Kampo medicines). Kampo medicines are primarily formulated with organic plant-based ingredients and are known to have fewer adverse reactions compared to Western medicine. In the near future, the aforementioned drugs may be recognized as Crimean-Congo hemorrhagic fever virus inhibitors following in vitro and in vivo examinations.

Abstract: In this work, the activity of extracts from S. edule var. nigrum spinosum, S. compositum, S. chinantlense, and the hybrid H-387-07 was evaluated against in vitro and in silico models related to leukemia. The cytotoxicity of extracts was analyzed by the crystal violet assay, whereas their effect on apoptosis was evaluated through flow cytometry approaches. The effect of treatment on the DNA fragmentation of representative leukemia cell lines was determined by electrophoresis. In silico modeling consisted of assessing the binding affinities between major components from the obtained extracts against CCR2. Results revealed that extracts from Sechium spp. can decrease the viability of J774 and P388 cell lines upon exposure to IC50 0.93-1.38 mg/mL. It was noted that extract from S. edule var. nigrum spinosum exhibited the highest capacity to induce the late apoptosis of J774 cells, whereas treatment with extract from S. chinantlense exerted the highest capability to cause early apoptosis of P388 cells. It was also determined that extracts caused the DNA fragmentation of the cell lines tested in this study after 68 h exposure to treatment. In silico evaluation evidenced that metabolites from extracts poses high affinity for chemokine-type receptors involved in the initiation and progression of leukemia exhibiting binding energies ranging from -7.89 to -9.49 kcal/mol. The retrieved evidence demonstrated the therapeutic capacity of Sechium spp. against leukemia considering in vitro and in silico mechanisms of action.

Abstract:

Shikonin, a naphthoquinone from Lithospermum erythrorhizon, exhibits broad anticancer potential through multiple regulated cell death pathways. It induces apoptosis via mitogen-activated protein kinase (MAPK) signalling, reactive oxygen species (ROS) accumulation, endoplasmic reticulum (ER) stress, and p53 activation, and also triggers necroptosis through receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), and mixed lineage kinase domain-like protein (MLKL), as well as ferroptosis and pyroptosis. Beyond cytotoxicity, shikonin suppresses metastasis by blocking epithelial–mesenchymal transition (EMT) and downregulating matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). It further disrupts tumour metabolism by targeting pyruvate kinase isoform M2 (PKM2) and modulating the Warburg effect. In combination, shikonin enhances the efficacy of chemotherapy (cisplatin, paclitaxel), targeted therapy (tamoxifen), and immunotherapy (anti-programmed cell death protein 1 [anti-PD-1]), thereby overcoming resistance. To address poor bioavailability, nanoparticles, liposomes, and derivatives such as β, β-dimethylacrylshikonin have been developed to improve potency and reduce toxicity. Preclinical studies show strong tumour regression in melanoma, breast, and ovarian cancer models. Although clinical validation remains limited, shikonin’s multifaceted actions, favourable safety, and therapeutic synergy highlight the need for rigorous clinical trials to define its oncological value.