Browsing by Author "Snigdha Singh"

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Exploring the Paradox of COVID-19 in Neurological Complications with Emphasis on Parkinson's and Alzheimer's Disease
(Hindawi Limited, 2022) Sachchida Nand Rai; Neeraj Tiwari; Payal Singh; Anurag Kumar Singh; Divya Mishra; Mohd. Imran; Snigdha Singh; Etrat Hooshmandi; Emanuel Vamanu; Santosh K. Singh; Mohan P. Singh
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a human coronavirus (HCoV) that has created a pandemic situation worldwide as COVID-19. This virus can invade human cells via angiotensin-converting enzyme 2 (ACE2) receptor-based mechanisms, affecting the human respiratory tract. However, several reports of neurological symptoms suggest a neuroinvasive development of coronavirus. SARS-CoV-2 can damage the brain via several routes, along with direct neural cell infection with the coronavirus. The chronic inflammatory reactions surge the brain with proinflammatory elements, damaging the neural cells, causing brain ischemia associated with other health issues. SARS-CoV-2 exhibited neuropsychiatric and neurological manifestations, including cognitive impairment, depression, dizziness, delirium, and disturbed sleep. These symptoms show nervous tissue damage that enhances the occurrence of neurodegenerative disorders and aids dementia. SARS-CoV-2 has been seen in brain necropsy and isolated from the cerebrospinal fluid of COVID-19 patients. The associated inflammatory reaction in some COVID-19 patients has increased proinflammatory cytokines, which have been investigated as a prognostic factor. Therefore, the immunogenic changes observed in Parkinson's and Alzheimer's patients include their pathogenetic role. Inflammatory events have been an important pathophysiological feature of neurodegenerative diseases (NDs) such as Parkinson's and Alzheimer's. The neuroinflammation observed in AD has exacerbated the Aβ burden and tau hyperphosphorylation. The resident microglia and other immune cells are responsible for the enhanced burden of Aβ and subsequently mediate tau phosphorylation and ultimately disease progression. Similarly, neuroinflammation also plays a key role in the progression of PD. Several studies have demonstrated an interplay between neuroinflammation and pathogenic mechanisms of PD. The dynamic proinflammation stage guides the accumulation of α-synuclein and neurodegenerative progression. Besides, few viruses may have a role as stimulators and generate a cross-autoimmune response for α-synuclein. Hence, neurological complications in patients suffering from COVID-19 cannot be ruled out. In this review article, our primary focus is on discussing the neuroinvasive effect of the SARS-CoV-2 virus, its impact on the blood-brain barrier, and ultimately its impact on the people affected with neurodegenerative disorders such as Parkinson's and Alzheimer's. © 2022 Sachchida Nand Rai et al.
Historical advancements in targeted nanoscale drug delivery systems
(Elsevier, 2025) Snigdha Singh; Pankaj Kalia; Raj N. Kumar; Swati Pundir; Vivek K. Chaturvedi; Anurag Kumar Singh; Rajendra Awasthı; Santosh Kumar Singh; Amit Kumar Singh
This inclusive examination of the evolution of nanoscale drug delivery systems (DDSs) elucidates the profound impact these technologies have exerted on modern medicine. From the seminal development of liposomal encapsulation in the 1960s to contemporary advancements in polymeric micelles, dendrimer-based carriers, and CRISPR–Cas9 delivery vectors, the progression of nanotechnology has markedly enhanced therapeutic precision and efficacy. Notable innovations, particularly in oncological applications, include the deployment of polyethylene glycol conjugation and stimuli-responsive nanocarriers, which have substantially improved the stability, pharmacokinetic profiles, and targeted delivery of therapeutic agents. Nonetheless, several challenges persist, including the scale-up of manufacturing processes, batch-to-batch reproducibility, and biocompatibility and toxicity concerns. The incorporation of artificial intelligence (AI) and machine learning (ML) into nanoparticle design and optimization offers a promising avenue for overcoming these obstacles. AI and ML methodologies have the potential to expedite the discovery of novel nanocarriers formulations, predict biological interactions with high accuracy, and streamline the development pipeline. As these technologies evolve, they may facilitate ground breaking advancements in the treatment of complex diseases such as malignancies, genetic disorders, and chronic conditions. The future landscape of nanomedicine is poised to offer increasingly personalized, efficacious, and safe therapeutic options, with emerging innovations such as nanorobots and biodegradable nanomaterials anticipated to revolutionize therapeutic paradigms. Continued research into the biodegradability and biocompatibility of nanomaterials is expected to address current limitations, ensuring that these advanced DDSs are both effective and safe for clinical applications. The advent of “smart” nanocarriers capable of real-time monitoring and adaptive responses to physiological fluctuations could further enhance therapeutic precision and patient outcomes. The ongoing evolution of nanoscale DDSs is poised to drive significant advancements in precision medicine, transforming disease management strategies and heralding a new era of therapeutic possibilities. © 2026 Elsevier Inc. All rights reserved.
In vitro profiling and molecular dynamics simulation studies of berberine loaded MCM-41 mesoporous silica nanoparticles to prevent neuronal apoptosis
(Royal Society of Chemistry, 2024) Anurag Kumar Singh; Snigdha Singh; Tarun Minocha; Sanjeev Kumar Yadav; Reema Narayan; Usha Yogendra Nayak; Santosh Kumar Singh; Rajendra Awasthi
Neuronal loss in Alzheimer's disease has been reported to display features of apoptosis, pyroptosis (programmed necrosis), or necroptosis. This study thoroughly examines the production and characterization of MCM-41 based berberine (BBR)-loaded porous silica nanoparticles (MSNs) by a modified Stöber method, focusing on their possible role in inhibiting the apoptotic process. Particle size, polydispersity index, morphology, drug loading, zeta potential, entrapment efficiency, and drug release were examined. The formulation was analyzed using various spectroscopic techniques. The surface area was computed by the Brunauer-Emmett-Teller plot. Computational models were developed for molecular dynamics simulation studies. A small PDI value indicated an even distribution of particles at nanoscale sizes (80-100 nm). Results from XRD and SEAD experiments confirmed the amorphous nature of BBR in nanoparticles. Nanoparticles had high entrapment (75.21 ± 1.55%) and drug loading (28.16 ± 2.5%) efficiencies. A negative zeta potential value (−36.861.1 mV) indicates the presence of silanol groups on the surface of silica. AFM findings reveal bumps due to the surface drug that contributed to the improved roughness of the MSNs-BBR surface. Thermal gravimetric analysis confirmed the presence of BBR in MSNs. Drug release was controlled by simple diffusion or quasi-diffusion. Molecular dynamics simulations confirmed the existence of diffused drug molecules. Cellular studies using SH-SY-5Y cells revealed dose-dependent growth inhibition. Fragmented cell nuclei and nuclear apoptotic bodies in DAPI-stained cells exposed to nanoparticles showed an increase in apoptotic cells. Flow cytometry analysis demonstrated a lower red-to-green ratio in SH-SY-5Y cells treated with nanoparticles. This suggests improved mitochondrial health, cellular viability restoration, and prevention of the apoptotic process. This study provides essential data on the synthesis and potential of MSNs loaded with BBR, which may serve as a viable therapeutic intervention for conditions associated with apoptosis. © 2024 RSC.
Intranasally Co-administered Berberine and Curcumin Loaded in Transfersomal Vesicles Improved Inhibition of Amyloid Formation and BACE-1
(American Chemical Society, 2022) Gaurav Mishra; Rajendra Awasthi; Anurag Kumar Singh; Snigdha Singh; Sunil Kumar Mishra; Santosh Kumar Singh; Manmath K. Nandi
Selective permeability of the blood-brain barrier restricts the treatment efficacy of neurologic diseases. Berberine (BBR) and curcumin (CUR)-loaded transferosomes (TRANS) were prepared for the effective management of Alzheimer's disease (AD). The study involved the syntheses of BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS by the film hydration method. Vesicles were characterized to ensure the formation of drug-loaded vesicles and their in vivo performance. The particle sizes of BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS were 139.2 ± 7, 143.4 ± 8, and 165.3 ± 6.5 nm, respectively. The presence of diffused rings in the SED image indicates the crystalline nature of the payload. Low surface roughness in an AFM image could be associated with the presence of a surface lipid. BBR-CUR-TRANS showed 41.03 ± 1.22 and 47.79 ± 3.67% release of BBR and 19.22 ± 1.47 and 24.67 ± 1.94% release of CUR, respectively, in phosphate buffer saline (pH 7.4) and acetate buffer (pH 4.0). Formulations showed sustained release of both loaded drugs. BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS exhibited a lower percentage of hemolysis than pure BBR and CUR, indicating the safety of the payload from delivery vesicles. Lower percentages of binding were recorded from BBR-CUR-TRANS than BBR-TRANS and CUR-TRANS. Acetylcholinesterase inhibition activity of the prepared transferosomes was greater than that of pure drugs, which are thought to have good cellular penetration. The spatial memory was improved in treated mice models. The level of malondialdehyde decreased in AD animals treated with BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS, respectively, as compared to the scopolamine-induced AD animals. BBR-CUR-TRANS-treated animals showed the highest decrease in the NO level. The catalase level was significantly restored in scopolamine-intoxicated animals treated with BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS. The immunohistochemistry result suggested that the BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS have significantly decreased the regulation of expression of BACE-1 through antioxidant activity. In conclusion, the study highlights the utility of formulated transferosomes as promising carriers for the co-delivery of drugs to the brain. © 2022 American Chemical Society. All rights reserved.
Introduction to nanogels: exploring the frontier of nanoscale technology
(Elsevier, 2025) Snigdha Singh; Anand Prakash Maurya; Anurag Kumar Singh; Vivek K. Chaturvedi; Jay Singh; Amit Kumar Singh; Santosh Kumar Singh
Drug delivery holds great promise for the development of nanogel-based platforms. Owing to their exceptional stability and efficient drug-loading capacity for both hydrophilic and hydrophobic agents, nanogels present significant opportunities for pharmaceutical innovation. As multifunctional systems, composite nanogels can deliver genes, drugs, and diagnostic agents, making them ideal platforms for multimodal theranostic applications. These nanogels can respond to various stimuli, enabling the controlled release of chemotherapy and immunotherapy drugs while reprogramming cells within the tumor microenvironment to suppress tumor growth, progression, and metastasis. Specific ligands can be attached to nanogels for active targeting to enhance drug accumulation and improve therapeutic precision, ultimately improving cancer treatment outcomes. Additionally, advanced “immune-specific” nanogels possess tumor tissue-editing capabilities, further refining targeted drug delivery. Integrating multifunctional nanogel-based delivery systems enhances the precision and effectiveness of immunotherapy and combination therapies, offering improved outcomes in tumor treatment. © 2025 Elsevier Ltd. All rights reserved.
Mango Leaves (Mangifera indica)-Derived Highly Florescent Green Graphene Quantum Dot Nanoprobes for Enhanced On-Off Dual Detection of Cholesterol and Fe2+ Ions Based on Molecular Logic Operation
(American Chemical Society, 2024) Ratneshwar Kumar Ratnesh; Mrityunjay Kumar Singh; Vinay Kumar; Snigdha Singh; Ramesh Chandra; Mandeep Singh; Jay Singh
In the present study, we have engineered a molecular logic gate system employing both Fe2+ ions and cholesterol as bioanalytes for innovative detection strategies. We utilized a green-synthesis method employing the mango leaves extract to create fluorescent graphene quantum dots termed “mGQDs”. Through techniques like HR-TEM, i.e., high-resolution transmission electron microscopy, Raman spectroscopy, and XPS, i.e., X-ray photoelectron spectroscopy, the successful formation of mGQDs was confirmed. The photoluminescence (PL) characteristics of mGQDs were investigated for potential applications in metal ion detection, specifically Fe2+ traces in water, by using fluorescence techniques. Under 425 nm excitation, mGQDs exhibited emission bands at 495 and 677 nm in their PL spectrum. Fe2+-induced notable quenching of mGQDs’ PL intensity decreased by 97% with 2.5 μM Fe2+ ions; however, adding 20 mM cholesterol resulted in a 92% recovery. Detection limits were established through a linear Stern-Volmer (S-V) plot at room temperature, yielding values of 4.07 μM for Fe2+ ions and 1.8 mM for cholesterol. Moreover, mGQDs demonstrated biocompatibility, aqueous solubility, and nontoxicity, facilitating the creation of a rapid nonenzymatic cholesterol detection method. Selectivity and detection studies underscored mGQDs’ reliability in cholesterol level monitoring. Additionally, a molecular logic gate system employing Fe2+ metal ions and cholesterol as a bioanalyte was established for detection purposes. Overall, this research introduces an ecofriendly approach to craft mGQDs and highlights their effectiveness in detecting metal ions and cholesterol, suggesting their potential as versatile nanomaterials for diverse analytical and biomedical applications. © 2024 American Chemical Society.
Nanomedicine at the Forefront: Transforming Brain Drug Delivery with Innovative Strategies
(CRC Press, 2024) Snigdha Singh; Anurag Kumar Singh; Anand Maurya; Vivek K. Chaturvedi; Jay Singh; Santosh Kumar Singh
Recent advancements in brain drug delivery have revolutionized the field of neuroscience and opened new avenues for the treatment of neurological disorders. Overcoming the blood-brain barrier (BBB) has been a significant challenge, but innovative techniques and technologies have emerged to enhance drug delivery to the brain. Nanoparticles and nanocarriers have been engineered to encapsulate drugs and transport them across the BBB, while ultrasound-assisted drug delivery using microbubbles has shown promise in inducing transient disruptions of the BBB. Neurosurgical implants have provided a means for localized drug delivery and continuous monitoring, while gene therapy approaches have allowed for targeted treatment of genetic-based neurological disorders. Brain-machine interfaces have emerged as cutting-edge technologies, enabling direct communication between the brain and external devices for drug delivery and other therapeutic interventions. These recent advancements offer great potential for improving the efficacy and precision of brain drug delivery, ultimately leading to enhanced treatment outcomes for patients with neurological disorders. © 2024 selection and editorial matter, Anurag Kumar Singh, Vivek K. Chaturvedi, and Jay Singh; individual chapters, the contributors.
Natural Polymeric Nanoparticles for Brain Targeting
(CRC Press, 2024) Gaurav K. Pandit; Ritesh K. Tiwari; Ashish Kumar; Veer Singh; Gufran Ahmed; Shazia Kazmi; Shaliha Irfan; Vishal Mishra; Anurag Kumar Singh; Snigdha Singh; Meenakshi Singh
Natural polymeric nanoparticles (NPNs) have arisen as promising transporters for brain focusing because of their biocompatibility and biodegradability (Singh et al., 2021a). These NPNs are produced using natural polymers like proteins, polysaccharides, and lipids, which proposition benefits over manufactured polymers concerning security and decreased immunogenicity. NPNs have the capacity to encapsulate various therapeutic agents, such as small molecules, peptides, and genes, and transport them to the brain in a targeted manner. Drug delivery to the brain is particularly challenging due to the presence of the blood-brain barrier (BBB), which restricts the entry of many drugs into the central nervous system (CNS). Brain. Nevertheless, NPNs have been shown to defeat the BBB through different components, including dynamic focusing on, detached focusing on, and transcytosis. Dynamic focusing on includes the alteration of the NPN surface with ligands that explicitly tie to receptors on the BBB, prompting endocytosis and transport across the BBB. Latent focusing on exploits the improved porousness and maintenance impact, which brings about the amassing of NPNs in the cerebrum because of the sluggish leeway of bigger particles from the BBB. Transcytosis is a cycle where NPNs are taken up by cerebrum microvascular endothelial cells and afterward shipped across the BBB into the CNS. NPNs have been examined for different brain neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, glioma, and various sclerosis. For instance, NPNs typifying little atom drugs, such as donepezil, have been shown to work on neurodegenerative disorders in Alzheimer’s disease models. Likewise, NPNs exemplifying restorative qualities have been utilized to convey quality treatment to the cerebrum for the treatment of Parkinson’s disease. NPNs have likewise been examined as vehicles for imaging specialists, for example, attractive reverberation imaging (X-ray) contrast specialists, and for the conveyance of radiotherapy to brain tumors. NPNs offer a promising methodology for brain targating because of their biocompatibility and biodegradability, and their capacity to embody differenttherupatic agents. The capacity of NPNs to penetrate in to the BBB and convey medications to the brain in a designated way has been shown in differentbrain disorders. brain However, additional research is required to enhance the design and formulation of NPNs for specific brain disorders and to fully realize their potential for drug delivery to the brain. © 2024 selection and editorial matter, Anurag Kumar Singh, Vivek K. Chaturvedi, and Jay Singh; individual chapters, the contributors.
Porous silicon nanocarriers for the management of neurodegenerative disorders
(Elsevier, 2025) Devinder Kumar; Raj N. Kumar; Sunil Dutt; Pankaj Kalia; Snigdha Singh; Anand Prakash Maurya; Anurag Kumar Singh; Rajendra Awasthı; Santosh Kumar Singh
Porous silicon (PSi) nanocarriers are gaining a lot of attention in nanomedicine for the treatment of neurodegenerative diseases (NDs). Aside from their complicated pathophysiology, NDs, such as Parkinson's and Alzheimer's, present unique challenges due to the difficulty for therapeutic agents to cross the blood–brain barrier. Since PSi nanocarriers have tunable porosity, biocompatibility, and biodegradability, they enable the effective loading and controlled release of a variety of therapeutic agents. Due to its porous structure and large surface area, peptides, nucleic acids, and small molecules are encapsulated in PSi, improving the bioavailability and therapeutic efficacy of the drugs. As recent findings show, it is now possible to make pSi nanoparticles to deliver neuroprotective agents directly to targeted neuronal cells, improving treatment outcomes. Delivery of therapeutics to specific brain regions can be enabled by functionalizing PSi with specific ligands or antibodies, improving its targeting capabilities. In addition, since conventional treatments often require high dosages and frequent administration, the ability of PSi nanocarriers to support sustained drug release can significantly reduce side effects. With PSi's controlled release profile, therapeutic drug levels can be maintained in the bloodstream for extended periods, improving patient compliance and overall treatment effectiveness. Pharmaceutical administration is not the only use for PSi nanocarriers; they have also shown promise in diagnostic applications, allowing simultaneous imaging and monitoring of treatment effects. Due to its dual purpose, PSi positions itself as a flexible platform for theranostic applications in of neurological diseases. Despite encouraging developments, there are still difficulties in the clinical implementation of PSi-based therapies. Research is presently being carried out on their synthesis and surface modification to improve the stability and mitigate the potential toxicity of pSi nanoparticles. To enable their integration into clinical practice, issues related to large-scale manufacturing and regulatory approval processes must also be resolved. © 2026 Elsevier Inc. All rights reserved.
Porous silicon-based drug delivery carriers in cancer management
(Elsevier, 2025) Bhaskar Sharma; Anjali Yadav; Srishti Jain; Nibha Singh; Shivani Gupta; Snigdha Singh; Anurag Kumar Singh
Recent advancements in cancer management have emphasized targeted therapies to improve treatment efficacy while minimizing side effects. Due to the unique properties such as high surface area, biocompatibility, and tunability, porous, silicon-based drug delivery carriers have gained attention in this field. This chapter provides an overview of targeted drug delivery in cancer treatment, particularly focusing on porous silicon (PSi) nanoparticles. With a nanosized porous structure, PSi nanoparticles offer high drug-loading capacity and controlled release, making them ideal candidates for delivering a wide range of therapeutic agents. Surface modification techniques enable active targeting of cancer cells, reducing off-target effects and improving the precision of treatment. PSi nanoparticles can be engineered to release drugs in response to specific stimuli in the tumor microenvironment, further enhancing therapeutic potential. An added advantage is their ability to combine drug delivery with diagnostic imaging facilitating real-time monitoring of treatment responses and enabling early diagnosis. © 2026 Elsevier Inc. All rights reserved.
Recent advances in NIR-II emitting nanomaterials: design and biomedical applications of lanthanide complexes and functionalized mesoporous silica nanoparticles (MSNs)
(Royal Society of Chemistry, 2025) Krishanu Bandyopadhyay; Snigdha Singh; Vivek K. Chaturvadi; Anurag Kumar Singh; Abhineet Verma
The second near-infrared (NIR-II, 1000-1700 nm) region has gained significant attention due to its superior tissue penetration depth, reduced photon scattering, and minimal autofluorescence compared to the first near-infrared (NIR-I, 700-900 nm) window. These advantages make NIR-II an ideal spectral range for bioimaging, photothermal therapy (PTT), and photodynamic therapy (PDT). Various nanomaterials, including metal-based complexes, organic dyes, and carbon-based materials, have been engineered to serve as efficient NIR-II agents for enhanced biomedical applications. Among these, mesoporous silica nanoparticles (MSNs) have emerged as versatile nanoplatforms due to their tunable porosity, high surface area, and biocompatibility. MSNs can be modified with different functional materials, such as luminescent coordination complexes, organic dyes, and metal nanoclusters, to optimize photothermal conversion efficiency and imaging capabilities. Their ability to encapsulate therapeutic agents further enables controlled drug delivery and combinational cancer therapies. Additionally, hybrid MSN systems incorporating nanocarbon materials (e.g., fullerenes, carbon nanotubes) and metal nanoparticles have been explored to enhance stability and bioavailability. Despite their promising potential, challenges such as long-term biocompatibility, clearance mechanisms, and precise targeting remain key hurdles in clinical translation. Future research should focus on overcoming these limitations by developing next-generation MSN-based nanocomposites, such as MSN-graphene oxide, MSN-fullerenes, MSN-carbon nanotubes, MSN-quantum dots, and MSN-metal nanoparticles. These advancements will pave the way for improved therapeutic efficacy and broader biomedical applications. © 2025 The Royal Society of Chemistry.
Recent advances in solar cell technology: addressing technological challenges, scenarios, and environmental implications in the development of sustainable energy solutions
(Royal Society of Chemistry, 2025) R. K. Ratnesh; R. Kumar; Snigdha Singh; Ramesh Chandra; Jay Singh
The exponential surge in energy demand, driven by technological progress and evolving lifestyles, has precipitated a critical juncture. Energy sourcing now spans the spectrum from conventional to renewable alternatives. The limitations of conventional sources, entwined with their contributions to ecological degradation, deforestation, and the amplification of global warming and climate change, have come to the forefront. In response, renewable energy sources have surged into prominence, capturing both industrial and scientific attention. This comprehensive review navigates through the labyrinth of technological hurdles, breakthroughs, and heightened efficiencies that characterize diverse solar cell (SC) paradigms. Importantly, this exploration encompasses SC materials grouped under II-VI, III-V, and perovskite categories. While these materials bear utility, their intrinsic carcinogenic nature raises alarms regarding potential ecological and health impacts. The imperative to cultivate ecologically mindful alternatives reverberates as a persistent motif, underscored by a dedicated focus on the maturation of environmentally friendly carbon-based SCs. In this study, a meticulous comparative investigation of pivotal performance indicators such as Voc, Isc, fill-factor, and efficiency is meticulously conducted. This assessment spans an expansive array of materials and substrates utilized within the realm of SCs. In a broader context, the ultimate aspiration of this paper is to untie the intricate interaction of factors that govern the trajectory of solar cell performance. By doing so, it serves as an illuminating guidepost, steering the course of inquiry and advancement in the domain of sustainable energy technologies. © 2025 The Royal Society of Chemistry.
Silibinin: a natural flavonoid with multifaceted anticancer potential and therapeutic challenges
(Springer, 2025) Snigdha Singh; Arpit Sharma; Tanu Pandey; Shivani Gupta; Alok Shukla; Santosh Kumar Singh; Amit Kumar Singh
Silibinin, the principal bioactive flavonolignan of Silybum marianum (milk thistle), has emerged as a promising natural agent with multifaceted anticancer potential. Extensive preclinical studies demonstrate its diverse pharmacological properties, including antioxidant, anti-inflammatory, and chemopreventive activities, which collectively contribute to its antitumor effects. At the molecular level, silibinin exerts cytotoxicity through the induction of apoptosis, involving both extrinsic (death receptor-mediated) and intrinsic (mitochondria-dependent) pathways. It modulates key signaling cascades such as EGFR, STAT3, and PI3K/AKT/mTOR, leading to suppression of proliferation, angiogenesis, invasion, and modulation of autophagy, stemness and Senescence. Importantly, silibinin acts as a modulator of apoptosis by restoring the balance between pro- and anti-apoptotic proteins, thereby sensitizing cancer cells to programmed cell death. Evidence across multiple malignancies, including hepatocellular carcinoma, breast, lung, and colorectal cancers etc, highlights its broad-spectrum therapeutic relevance. Clinical studies, though limited, suggest that silibinin may enhance the efficacy of standard chemotherapeutic, radiotherapeutic, and targeted regimens while reducing associated toxicities, underscoring its role as a synergistic adjuvant. However, challenges such as poor bioavailability, variable pharmacokinetics, and limited large-scale clinical validation constrain its translational application. To address these limitations, novel strategies such as nanocarrier-based delivery, structural modifications, and combination therapies are being actively investigated. Overall, silibinin represents a compelling natural flavonoid with dual preventive and therapeutic roles in oncology, though future research must overcome pharmacological barriers to fully harness its clinical potential. (Figure presented.) © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.