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Targeted rapid degradation of bilirubin has the potential to thwart incipient bilirubin encephalopathy. We investigated a novel spinel-structured citrate-functionalized trimanganese tetroxide nanoparticle (C-MnSevere neonatal unconjugated hyperbilirubinemia (SNH) was induced in neonatal C57BL/6j mice model with phenylhydrazine (PHz) intoxication. Efficiency of the nanodrug on both in vivo bilirubin degradation and amelioration of bilirubin encephalopathy and associated neurobehavioral sequelae were evaluated.Single oral dose (0.25 mg kgThis study demonstrates the in vivo capacity of this novel nanodrug to reduce systemic and neural bilirubin load and reverse bilirubin-induced neurotoxicity. Further compilation of a drug-safety-dossier is warranted to translate this novel therapeutic chemopreventive approach to clinical settings.None of the current pharmacotherapeutics treat severe neonatal hyperbilirubinemia (SNH) to prevent risks of neurotoxicity. In this preclinical study, a newly investigated nano-formulation, citrate-functionalized Mn more...

Purpose: The aim of the investigation was to find out the degree of toxicity of the herbal composite for humans, animals, or the environment. Acute and 28 days repeated sub-acute oral toxicity study of herbal composite (Herbodil®) carried out as per the current OECD guidelines.Materials and Methods: 2000mg/kg of the herbal composite was orally administered to the animals to find out the acute toxicity. The treated animals were observed for toxic signs at thirty min, one, two and four hours and thereafter once a day for the next 14 days. In sub-acute study i.e.,28 days repeated dose oral study, the mice were segregated into four groups (two set for each sex) of six mice each. Group-1 mice served as a control (untreated). Group II mice consumed lower dose of herbal composite i.e., 100 mg/kg, Group III mice consumed middle/moderate dose i.e., 200 mg/kg and Group IV mice received high dose of 400 mg/kg (orally) once daily for 28 days respectively.Results: This experimental in vivo study confirm that neither the acute toxicity study of herbal composite at the dose level of 2000mg/kg nor the sub-acute 28 days oral toxicity study developed any toxic signs, behavioural changes, or mortality during the whole study. Haematological and biochemical parameters dose not changes during the sub-acute study. Relative body weight of the mice also not change after the study.Conclusion: Experimental results obtained from the current investigation suggest that LD50 of developed herbal composite was >2000 mg /kg and the herbal composite is completely safe and non-toxic for therapy. more...

Since the first outbreak of SARS-CoV2, Severe Acute Respiratory Syndrome Coronavirus-2 in Wuhan, China in the December 2019, the world continues to be in state of fear, uncertainty, tension and anxiety till date and this state might continue because of emerging mutants. The vaccination drive all over the world is continuing, still the new variants are cause of concern, with the aim to prevent the spread of the virus, focus should be on techniques and processes which helps in strengthening our defense mechanism, the immune system. It has becoming clear from several studies that the immune system is greatly impacted by the COVID-19 infection through several inflammatory reactions. The role of balanced diet full of nutrients cannot be overlooked in controlling infectious diseases. A balanced diet which should include plant foods, vitamins and micronutrients and this review wants to emphasize on the preventive role played by the plant foods, vitamins and minerals in COVID-19 infections, to reduce the mortality rate as well as the morbidity in patients who are infected. more...

A crucial balance between oxidative eustress and distress is important for maintaining redox homeostasis in the cellular milieu. Therefore, sustaining the intracellular redox buffer condition with exogenous agents could be a therapeutic strategy against diseases caused by redox imbalance. Here, we synthesized chitosan-functionalized Mn3O4 nanoparticles (Ch-Mn3O4 NPs) and tested their redox buffering capability in in-vitro and in-cellulo. Chitosan is easily absorbed by the intestine and can be used as a target-specific delivery agent to the intestine, while Mn3O4 NPs have redox modulatory properties. Therefore, combination of chitosan and Mn3O4 NPs provide the opportunity for targeted redox buffering. Targeted delivery of a drug and remediation of the corresponding indication qualify the drug to be a theranostic agent. Our spectroscopic studies suggest ROS generation as well as antioxidant ability of Ch-Mn3O4 NPs. In-cellulo studies using A549 cell lines confirmed the efficacy of the nanohybrid in redox homeostasis. The outcomes suggest that Ch-Mn3O4 nanohybrid has the potential to function as a target-specific redox buffering agent in both in-vitro and in-cellulo systems. more...

Objectives: Hepatic dysfunction is a critical public health problem affecting the global population, characterized by excessive deposition of extracellular matrix components due to increased matrix production and decreased matrix degradation. The present work was aimed to evaluate hepatoprotective effect of AKSS16-LIV01 a newly developed multiherbal formulation against carbon tetrachloride (CCl4)-induced liver dysfunction in Swiss albino mice to establish it as a bench to bedside formulation catering to the various facets of hepatic malfunction. Methods: Thirty-six Swiss adult albino Wister mice divided into six groups. Group-I control untreated animals, Group-II received AKSS16-LIV01 (400 mg/kg), Group-III received CCl4 (1 ml/kg-bw), Group-IV received AKSS16-LIV01 (200 mg/kg) after 2 weeks CCl4 induction, Group-V received AKSS16-LIV01 (400 mg/kg) after 2 weeks CCl4 induction, and Group-VI received standard drug silymarin (100 mg/kg). At the end of the experimental period, all the animals were fasted overnight and blood was collected through retro-orbital plexus for preparation of serum and was analyzed for biochemical parameters, lipid profile, and total plasma protein. Liver tissue was collected for histological study. Results: The combined plant extract including six Indian medicinal herbs and three medicinal spices (AKSS16-LIV01) showed significant hepatoprotective effect by controlling the various essential biochemical parameters in serum. Moreover, treatment with AKSS16-LIV01 raised the level of serum total protein, normalizes the serum biochemical and lipid profiles parameters. Pre-treatment with AKSS16-LIV01 in mice also restored the alteration of various liver parameters such as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, blood urea nitrogen, total bilirubin, and direct bilirubin on CCl4-induced liver damage. Gross liver morphology and normal histological examination of the liver also supported hepatic protection by AKSS16-LIV01. Conclusion: Taken together, these results suggest that AKSS16-LIV01 may induce remarkable protective effects against hepatic injury induced by CCl4 treatment. more...

Background: Tramadol hydrochloride/paracetamol (THP) a fixed dose combination (FDC) is widely spread analgesic used to treat moderate to moderately severe pain. Over dose or chronic use of this fixed dose combination produce serious adverse effects. An acute Tramadol hydrochloride/paracetamol (THP) overdose can lead to a fatal liver damage. Objectives: There is a worldwide need to develop a safe and symptomatic medication which controls the different medical complications. Materials and Methods: Healthy adult swiss albino mice were assigned to four groups of six mice each according to their weights. Group-I serve as control, Group-II received Multi herbal formulation (AKSS16 LIV01) 400 mg/kg/day, Group-III received Tramadol hydrochloride/paracetamol (THP) 1.68 g / 300ml water and Group-IV received THP along with AKSS16-LIV01 (400 mg/kg). Blood samples were collected from the retro orbital plexus of each animal to determine various blood parameters and liver transaminase. Results: Administration of THP showed decline body weight, food consumption and water intake in mice whereas treatment with Multi herbal formulation (AKSS16-LIV01) normalized the same as compared with untreated animals. Treatment with THP (Group-III) decline the packed cell volume (PCV), haempglobin (Hb), means cell volume (MCV), means cell hemoglobin (MCH) and greater the white blood cell (WBC) compared with control. Pre-treatment with AKSS16-LIV01 significantly (p more...

Background: Hepatotoxicity is one of the common side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Scientific study stated that hepatotoxicity is the most serious adverse effects of Aceclofenac. Objectives: In this study, our aim was to investigate the use of Fortibile® tablet containing ursodeoxycholic acid (UDCA) in prevention of the hepatotoxic effect and biochemical changes induced by aceclofenac (ACE) in laboratory mice. Materials and Methods: Swiss albino mice were divided into four groups (control, UDCA (Fortibile® tablet) 20 mg/kg, aceclofenac (ACE) 50mg/kg, UDCA 20 mg/kg + aceclofenac 50 mg/kg). Results: Administration of aceclofenac (ACE) showed decline body weight, food consumption, water intake and elevated liver weight in mice whereas treatment with UDCA (Fortibile® tablet) normalized the same as compared with untreated animals. Animals treated with aceclofenac caused elevated activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) as well as total and direct bilirubin level. These elevations in liver enzymes were decreased by combination of aceclofenac with UDCA. On the other hand application of aceclofenac (ACE) on mice caused a significant increase in serum and tissue malondialdehyde (MDA) and nitric oxide (NO) content but significant decrease in glutathione GSH and GPx content. Combine thepary of UDCA and aceclofenac resulted in a significant decrease in MDA, NO content and significantly elevated GSH and GPx content. Conclusion: It could be concluded that Fortibile® tablet containing Ursodeoxycholic acid acts as an effective hepatoprotective agent against NSAIDs induced liver dysfunction, and this effect might be related to its antioxidant properties. Hepatic functions should be monitored, and the dose should be adjusted during aceclofenac (ACE) therapy. Keywords: Ursodeoxycholic acid, Aceclofenac, Hepatotoxicity, Liver function test, Oxidative stress more...

Haematological disorders and related complications are very common phenomenon against hazardous chemicals. Alteration of hematologic parameters disrupts the body’s normal homeostasis. There is a worldwide need to develop a safe and symptomatic medication which controls the haematological complications. Healthy adult Swiss albino mice were assigned to four groups of six mice each according to their weights. Group-I serve as control, Group-II received multi herbal formulation (AKSS16-LIV01) 400 mg/kg/day, Group-III received carbon tetrachloride (CCl4) 1 ml/kg-bw and Group-IV received CCl4 along with AKSS16-LIV01 (400 mg/kg). Blood samples were collected from the retro orbital plexus of each animal to determine various blood parameters and liver transaminase. Administration of carbon tetrachloride (CCl4) showed decline body weight, food consumption and water intake in mice whereas treatment with multi herbal formulation (AKSS16-LIV01) normalized the same as compared with untreated animals. Treatment with CCl4 (Group-III) decline the packed cell volume (PCV), haemoglobin (Hb), means cell volume (MCV), means cell hemoglobin (MCH) and greater the white blood cell (WBC) compared with control. Pre-treatment with AKSS16-LIV01 significantly (p more...

Attachment of microbial bodies including the corona virus on the surface of personal protective equipment (PPE) is found to be potential threat of spreading infection. Here, we report the development of a triboelectroceutical fabric (TECF) consisting of commonly available materials, namely, nylon and silicone rubber (SR), for the fabrication of protective gloves on the nitrile platform as model wearable PPE. A small triboelectric device (2 cm × 2 cm) consisting of SR and nylon on nitrile can generate more than 20 V transient or 41 μW output power, which is capable of charging a capacitor up to 65 V in only ∼50 s. The importance of the present work relies on the TECF-led antimicrobial activity through the generation of an electric current in saline water. The fabrication of TECF-based functional prototype gloves can generate hypochlorite ions through the formation of electrolyzed water upon rubbing them with saline water. Further, computational modelling has been employed to reveal the optimum structure and mechanistic pathway of antimicrobial hypochlorite generation. Detailed antimicrobial assays have been performed to establish effectiveness of such TECF-based gloves to reduce the risk from life-threatening pathogen spreading. The present work provides the rationale to consider the studied TECF, or other materials with comparable properties, as a material of choice for the development of self-sanitizing PPE in the fight against microbial infections including COVID-19. © 2021 American Chemical Society. more...

Nanomedicine, the offspring born from the marriage of nanotechnology and medicine, has already brought momentous advances in the fight against a plethora of unmet diseases from cardiovascular and neurodegenerative to diabetes and cancer. Here, we review a conceptual framework that will provide a basic understanding about the molecular mechanism of action of a therapeutic nanomaterial inside biological milieu. In this review, we highlight how the catalytic nature of a transition metal oxide nanomaterial influences the cellular redox homeostasis, supports the cellular antioxidant defence system and reactivates the reactive oxygen species (ROS) mediated signalling to perform normal cell functions like cell cycle, differentiation, apoptosis, inflammation, toxicity, and protein interactions. With numerous examples, we describe the redox modulatory nature of d-block metal oxide nanomaterials and their biomimetic nanozyme activities to protect the mitochondria, the cellular redox mediator which prevents an organism from various diseases. This knowledge will be useful to design new nanomaterials capable of intracellular redox modulation, which in turn can be effective therapeutic agents for treatment of various unmet diseases that are beyond the ability of modern synthetic medicine. more...

Precise control of intracellular redox status, i.e., maintenance of physiological level of reactive oxygen species (ROS) for mediating normal cellular functions (oxidative eustress) while evading the excess ROS stress (distress) is central to the concept of redox medicine. In this regard, engineered nanoparticles with unique ROS generation, transition, or depletion functions have the potential to be the choice of redox therapeutics. However, it is always challenging to estimate whether ROS-induced intracellular events are beneficial or deleterious to the cell. Here, we propose the concept of redox buffering capacity as a therapeutic index of engineered nanomaterials. As a steady redox state is maintained for normal functioning cells, we hypothesize that the ability of a nanomaterial to preserve this homeostatic condition will dictate its therapeutic efficacy. Additionally, the redox buffering capacity is expected to provide information about the nanoparticle toxicity. Here, using citrate functionalized trimanganese tetroxide nanoparticles (C-Mn3O4 NPs) as a model nanosystem we explored its redox buffering capacity in erythrocytes. Furthermore, we went on to study the chronic toxic effect (if any) of this nanomaterial in animal model in order to co-relate with the experimentally estimated redox buffering capacity. This study could function as a framework for assessing the capability of a nanomaterial as redox medicine (whether maintains eustress or damages by creating distress), thus orienting its application and safety for clinical use. more...

Centers for Disease Control and Prevention (CDC) warns the use of one-way valves or vents in free masks for potential threat of spreading COVID-19 through expelled respiratory droplets. Here, we have developed a nanoceutical cotton fabric duly sensitized with non-toxic zinc oxide nanomaterial for potential use as membrane filter in the one way valve for the ease of breathing without the threat of COVID-19 spreading. A detailed computational study revealed that zinc oxide nanoflowers (ZnO NF) with almost two-dimensional petals trap SARS-CoV-2 spike proteins, responsible to attach to ACE-2 receptors in human lung epithelial cells. The study also confirm significant denaturation of the spike proteins on the ZnO surface, revealing removal of virus upon efficient trapping. Following the computational study, we have synthesized ZnO NF on cotton matrix using hydrothermal assisted strategy. Electron microscopic, steady-state and picosecond resolved spectroscopic studies confirm attachment of ZnO NF to the cotton (i.e., cellulose) matrix at atomic level to develop the nanoceutical fabric. A detailed antimicrobial assay using Pseudomonas aeruginosa bacteria (model SARS-CoV-2 mimic) reveals excellent anti-microbial efficiency of the developed nanoceutical fabric. To our understanding the novel nanoceutical fabric used in one-way valve of a face mask would be the choice to assure breathing comfort along with source control of COVID-19 infection. The developed nanosensitized cloth can also be used as antibacterial/anti CoV-2 washable dress material in general.GRAPHICAL ABSTRACTA novel nanoceutical cotton fabric duly sensitized with non-toxic zinc oxide nanoflower can potentially be used as membrane filter in the one way valve of face mask to assure breathing comfort along with source control of COVID-19 infection. The nanoceutical fabric denatures the SARS-CoV-2 spike protein and makes the microorganism ineffective. more...

Targeting reactive oxygen species (ROS) while maintaining cellular redox signaling is crucial in the development of redox medicine for the therapeutic benefit as the origin of several prevailing diseases including chronic kidney disease (CKD) is linked to ROS imbalance and associated mitochondrial dysfunction. Here, we have shown that an indigenously developed nanomedicine comprising of Mn3O4nanoparticles duly functionalized by biocompatible ligand citrate (C-Mn3O4NPs) can maintain cellular redox balance in an animal model. We developed a cisplatin-induced CKD model in C57BL/6j mice where severe mitochondrial dysfunction resulting in oxidative distress lead to the pathogenesis. Four weeks of treatment with C-Mn3O4NPs restored renal function, preserved normal kidney architecture, ameliorated overexpression of pro-inflammatory cytokines, and arrested glomerulosclerosis and interstitial fibrosis in CKD mice. A detailed study involving human embryonic kidney (HEK 293) cells and isolated mitochondria from experimental animals revealed that the molecular mechanism behind the pharmacological action of the nanomedicine involves protection of structural and functional integrity of mitochondria from oxidative damage, the subsequent reduction in intracellular ROS, and maintenance of cellular redox homeostasis. To the best of our knowledge, such studies that efficiently treated a multifaceted disease like CKD using a biocompatible redox nanomedicine are sparse in the literature. Successful clinical translation of this nanomedicine may open a new avenue in redox-mediated therapeutics of several other diseases (e.g., diabetic nephropathy, neurodegeneration, and cardiovascular disease) where oxidative distress plays a central role in pathogenesis. more...

Attachment of microbial bodies including coronavirus on the surface of personal protective equipment (PPE) is found to be potential threat of spreading infection. Here, we report the development of a novel tribo-electroceutical fabric (TECF) consisting of commonly available materials namely Nylon, and Silicone Rubber (SR) for the fabrication of protective gloves on Nitrile platform, as a model wearable PPE. A small triboelectric device (2 cm × 2 cm) consisting of SR and Nylon on Nitrile can generate more than 20 volt transient or 41 µW output power, which is capable of charging a capacitor up to 65 V in only ∼50 sec. The novelty of the present work relies on the TECF led anti-microbial activity through the generation of an electric current in saline water. The fabrication of TECF based functional prototype gloves can generate hypochlorite ions through the formation of electrolysed water upon rubbing them with saline water. Further a computational modelling has been employed to reveal the optimum structure and mechanistic pathway of anti-microbial hypochlorite generation. Detailed anti-microbial assays have been performed to establish effectiveness of such TECF based gloves to reduce the risk from life threatening pathogen spreading. The present work provides the rationale to consider the studied TECF, or other material with comparable properties, as material of choice for the development of self-sanitizing PPE in the fight against microbial infections including COVID-19. more...

BackgroundTargeted degradation of bilirubinin vivomay enable safer and more effective approach to manage incipient bilirubin encephalopathy consequent to severe neonatal hyperbilirubinemia (SNH). This report builds on the use of a spinel structured mixed-valence transition metal oxide (trimanganese tetroxide) nanoparticle duly functionalized with biocompatible ligand citrate (C-Mn3O4NP) having the ability to degrade bilirubin without photo-activation.MethodThe efficiency of C-Mn3O4NP inin vivodegradation of serum bilirubin and amelioration of severe bilirubin encephalopathy and associated neurobehavioral changes was evaluated in C57BL/6j animal model of SNH.ResultsOral single dose (0.25 mg kg-1body weight) of the NPs efficiently reduced serum bilirubin levels (both conjugated and unconjugated) in study mice. It prevents bilirubin-induced neurotoxicity with reduction of SNH as observed by neurobehavioral and movement studies of SNH-mice. Pharmacokinetic data suggests intestinal reabsorption of the NPs and explain sustainable action. Biodistribution, pharmacokinetics, and biocompatibility of the NPs were tested during sub-chronic exposure.ConclusionThus, we report preliminary studies that explore an affordable chemoprevention mechanism to acutely prevent or minimize bilirubin neurotoxicity in newborn infants.IMPACT STATEMENTDespite several attempts, no pharmaco-therapeutics are available for the treatment of severe neonatal hyperbilirubinemia (SNH) and associated neurotoxicity.Our newly developed nanodrug, citrate functionalized Mn3O4nanoparticles (C-Mn3O4NPs), can efficiently ameliorate SNH and associated neurotoxicity as investigated in preclinical rodent model.Chemoprevention effect of the nanodrug is found to be safe and sustainable.If successfully translated into clinical trials, C-Mn3O4NPs could become the first drug to treat SNH. more...

Treatment of cancer using nanoparticles made of inorganic and metallic compounds has been increasingly used, owing to their novel intrinsic physical properties and their potential to interact with specific cellular sites, thereby significantly reducing severe secondary effects. In this study, we report a facile strategy for synthesis of folate capped Mn3O4 nanoparticles (FA-Mn3O4 NPs) with high colloidal stability in aqueous media using a hydrothermal method for potential application in photodynamic therapy (PDT) of cancer. The capping of FA to Mn3O4 NPs was confirmed using various spectroscopic techniques. In adenocarcinomic human alveolar basal epithelial cells (A549), the nanohybrid synthesised with a combination of FA and Mn3O4 shows remarkable PDT activity via intracellular ROS generation (singlet oxygen). As established by a DNA fragmentation assay and fluorescence studies, the nanohybrid can cause significant nuclear DNA damage by light induced enhanced ROS generation. In the assessment of Bax, Bcl2 provides strong evidence of apoptotic cellular death. Cumulatively, the outcomes of this study suggest that these newly synthesized FA-Mn3O4 NPs can specifically destroy cells with overexpressed folate receptors, thereby providing a solution in the journey of cancer eradication. more...

Oxygen is one of the most significant elements for life because almost all living organisms utilize oxygen for respiration and energy generation. However, some derivatives of oxygen including free radicals called reactive oxygen species (ROS) are detrimental and cause several diseases such as neurodegeneration, diabetes, cancer and atherosclerosis. Oxidative stress is essentially an inability of our body to counteract or detoxify the harmful effects of ROS through neutralization by antioxidants. Till date direct in-vivo measurements of oxidative stress are challenging. In this work, we have developed a novel 2,7-dichlorodihydrofluorescein (DCFH) impregnated genomic DNA-based biomaterial, which is completely insoluble in water and forms excellent thin film layers on optical fiber tips. The biomaterial-sensitized fiber tip fluoresces brightly in the proximity of ROS as the entrapped DCFH is oxidized to highly fluorescent DCF. We have demonstrated that an indigenously developed biomaterial-sensitized optical fiber tip can work as an efficient ROS/oxidative stress sensor in an aqueous medium as well as in the blood phantom (hemoglobin solution). A preclinical study on the minimally invasive direct in-vivo oxidative stress detection in mice model has also been successfully demonstrated. more...

Nano technology possesses several branches including nanomedicine, which is the most promising field in the future medicine and is a probable therapeutic agent in prevention and medication of life threatening diseases through ROS inhibition. Therapeutic potential and antioxidant activity of Silver Nanoparticle coupled with Andrographis paniculata (AP-Ag NP) was assessed against CCl4 induced oxidative stress at tissue level. The main aim and objective of the study is to find out the comparative efficacy of AP-Ag NP against carbon tetrachloride (CCl4) induced oxidative stress model. Carbon tetrachloride (CCl4) was administered upon Swiss albino mice (male) for 28 days concurrently with AP-Ag NP (50 mg/kg body weight) orally to evaluate the therapeutic effects on hepatic oxidative injury, antioxidant potential and heme synthesis pathway. Serum ROS level was significantly elevated and blood and liver superoxide dismutase (SOD), catalase (CAT) activity and GSH level also significantly decreased after exposure of carbon tetrachloride (CCl4). Treatment with AP-Ag NP, as nano-antioxidant significantly increased SOD, CAT activity and GSH levels which indicate the recovery of oxidative injury and indicates restoring inhibited aminolevulinate dehydratase (ALAD) activity. In conclusion our results suggest that Silver Nanoparticle synthesized using Andrographis paniculata (AP-Ag NP) have the potential antioxidant effect in experimental animals. more...

Human exposure to heavy metals can cause a variety of life-threatening disorders, affecting almost every organ of the body, including the nervous, circulatory, cardiac, excretory, and hepatic systems. The presence of heavy metal (cause) and induced oxidative stress (effect) are both responsible for the observed toxic effects. The conventional and effective way to combat heavy metal overload diseases is through use of metal chelators. However, they possess several side effects and most importantly they fail to manage the entire causality. In this study, we introduce citrate-functionalized Mn3 O4 nanoparticles (C-Mn3 O4 NPs) as an efficient chelating agent for treatment of heavy metal overload diseases. By means of UV/Vis absorbance and steady-state fluorescence spectroscopic techniques we investigated the efficacy of the NPs in chelation of a model heavy metal, lead (Pb). We also explored the retention of antioxidant properties of the Pb-chelated C-Mn3 O4 NPs using a UV/Vis-assisted DPPH assay. Through CD spectroscopic studies we established that the NPs can reverse the Pb-induced structural modifications of biological macromolecules. We also studied the in vivo efficacy of NPs in Pb-intoxicated C57BL/6j mice. The NPs were not only able to mobilize the Pb from various organs through chelation, but also saved the organs from oxidative damage. Thus, the C-Mn3 O4 NPs could be an effective nanotherapeutic agent for complete reversal of heavy-metal-induced toxicity through chelation of the heavy metal and healing of the associated oxidative stress. more...

Treatment of cancer using nanoparticles made of inorganic and metallic compounds has been increasingly used, owing to their novel intrinsic physical properties and their potential to interact with specific cellular sites, thereby significantly reducing severe secondary effects. In this study, we report a facile strategy for synthesis of folate capped Mn more...

The potentiality of nano-enzymes in therapeutic use has directed contemporary research to develop a substitute for natural enzymes, which are suffering from several disadvantages including low stability, high cost, and difficulty in storage. However, inherent toxicity, inefficiency in the physiological milieu, and incompatibility to function in cellular enzyme networks limit the therapeutic use of nanozymes in living systems. Here, we have shown that citrate functionalized manganese-based biocompatible nanoscale material (C-Mn3O4 NP) efficiently mimics glutathione peroxidase enzyme in the physiological milieu and easily incorporates into the cellular multienzyme cascade for H2O2 scavenging. A detailed computational study reveals the mechanism of the nanozyme action. We further established the in vivo therapeutic efficacy of C-Mn3O4 nanozyme in a preclinical animal model of Huntington’s disease, a prevalent progressive neurodegenerative disorder, which has no effective medication till date.SUMMARYAlthough, nano-enzymes have shown lots of promises in the management of several diseases, two major concerns limit their clinical translation. Apart from the inherent toxicity of the constituent materials (e.g., cerium, vanadium, gold, etc.), activities of contemporary nanozymes are often inhibited in physiological milieu. Furthermore, most of them are incapable of incorporation into the cellular metabolic networks for functioning in tandem and parallel with natural enzymes, a major criteria for potential therapeutics.Here, we have shown that citrate-functionalized spherical Mn3O4 nanoparticles can efficiently mimic glutathione peroxidase (GPX) enzyme without the limitations of contemporary nanozymes, and effectively manage neurodegenerative Huntington’s disease in preclinical animal model. The choice of the material in the nanozyme lies on the fact that Mn is an essential micronutrient for mammals, and the stabilizing ligand citrate helps the nanoparticles to cross the blood-brain-barrier to reach brain. We have shown that the nanozyme can easily be incorporated in cellular antioxidant enzyme cascade. The specificity and efficacy of the nanozyme in the cascade was significantly higher compared to other reported nanozymes. We have justified our experimental findings with a detailed computational study. Understanding the mode of operation and management of Huntington’s disease in preclinical animal trial using a biocompatible (non-toxic) nanozyme as a part of the metabolic network may uncover a new paradigm in nanozyme based therapeutic strategy. more...

Correction for ‘Manganese neurotoxicity: nano-oxide compensates for ion-damage in mammals’ by Aniruddha Adhikari et al., Biomater. Sci., 2019, 7, 4491–4502, DOI: 10.1039/C9BM01039D.

‘Bottom-up’, i.e., molecule to medicine strategy for the discovery of new drugs takes enormous time and cost. In most of the cases, inherent toxicity and undesired side effects of the developed drug hinder its way beyond the early stages of development. In this regard, the systems pharmacology can play an excellent role by reducing the cost and time of drug development through rationalization and/or repurposing of traditional drugs with known side effects. In the present study, our aim was to develop an integrated systems biology method for the prediction of active ingredients of a traditional medicine and their potential targets inside the body. Further, we evaluated the predictive capacity of the developed method in a preclinical animal model. Here, we have prepared a formulation (SKP17LIV01) from an extract of eight medicinal plants traditionally used as liver medicine and identified the constituents using UHPLC-MS technique. Using systems biology approach, we have rationalized the components of the formulation for potential use in the treatment of heavy metal-induced hepatotoxicity. The active ingredients and potential therapeutic targets were also predicted. A detailed biochemical, histopathological and molecular study on the mice model of lead toxicity confirms the efficacy of the formulation as per prediction by the systems pharmacology approach. The study may open a new frontier for re-discovery of drugs that are already used in traditional medicine. more...