Displaying publications 61 - 80 of 286 in total

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  1. Acacia catechu seed extract provokes cytotoxicity via apoptosis by intrinsic pathway in HepG2 cells
    Thangavelu L, Geetha RV, Devaraj E, Dua K, Chellappan DK, Balusamy SR
    Environ Toxicol, 2022 Mar;37(3):446-456.
    PMID: 34800081 DOI: 10.1002/tox.23411
    Acacia catechu Willd (Fabaceae) is a thorny tree widely distributed in India and commonly used as traditional Ayurvedic medicine for various ailments. The current study evaluates the cytotoxic potentials of A. catechu ethanolic seed extract (ACSE) in HepG2 cells, a human hepatocellular carcinoma cell line. The HepG2 cells were treated with 0.1, 0.3, 1, 3, 10, 30, 100, 300 and 1000 μg/ml of ACSE and the cytotoxic effect was evaluated by MTT and lactate dehydrogenase (LDH) leakage assays. The IC50 of ACSE was found at 77.04 μg/ml and therefore, further studies were carried out with the concentrations of 35 and 70 μg/ml. The intracellular reactive oxygen species (ROS) generation and apoptosis-related morphological changes were evaluated. Gene expressions of Bax, Bcl-2, cytochrome C (Cyt-c), caspases-9 and 3 were analyzed by qPCR. The ACSE treatments caused LDH leakage was associated with an increased ROS generation. The increased ROS generation was associated with the downregulation of intracellular antioxidant enzyme superoxide dismutase and reduced glutathione content. AO/EB and PI staining also confirmed chromatin condensation and apoptosis. The flow cytometric analysis showed an accumulation of HepG2 cells at sub G0/G1 (apoptotic) phase upon ACSE treatments. The ACSE induced cytotoxicity and oxidative stress were related to increased apoptotic marker gene expressions such as Bax, Cyt-c, caspase-9 and 3, and decreased anti-apoptotic marker Bcl-2. The current finding suggests that ACSE has apoptosis-inducing potential via the mitochondrial pathway in HepG2 cells.
  2. Fulltext Emerging cases of mucormycosis under COVID-19 pandemic in India: Misuse of antibiotics
    Gupta G, S R, Singh Y, Thangavelu L, Singh SK, Dureja H, et al.
    Drug Dev Res, 2021 11;82(7):880-882.
    PMID: 34323298 DOI: 10.1002/ddr.21862
    COVID-19's second wave had a significant impact on India, on May 7, 2021, the largest daily recorded case count was a little more than 4 million, and it has since fallen. Although the number of new cases reported has dropped, during the third week of May 2021, India accounted for about 45% of new cases identified globally and around 34% of deaths. As India maintains its present level of stability, a new urgent threat has emerged in the form of coronavirus-associated mucormycosis. Mucormycosis, an acute and deadly fungal infection caused by Mucorales-related fungal species, is a fungal emergency with a particularly aggressive propensity for contiguous spread, associated with a poor prognosis if not properly and immediately identified, and treated. Mucormycosis, sometimes referred to as the "black fungus," has increased more rapidly in India during the second wave of COVID-19 than during the first wave, with at least 14,872 cases as of May 28, 2021. Uncontrolled diabetic mellitus (DM) and other immunosuppressive diseases such as neutropenia and corticosteroid treatment have traditionally been identified as risk factors for mucormycosis. Therefore, the use of glucocorticoids or high doses of glucocorticoids in mild COVID-19 cases (without hypoxemia) should be avoided. In addition, drugs that target the immune pathway, such as tocilizumab, are not recommended without clear benefits.
  3. Pharmaceutical Aspects of Green Synthesized Silver Nanoparticles: A Boon to Cancer Treatment
    Mishra V, Nayak P, Singh M, Tambuwala MM, Aljabali AA, Chellappan DK, et al.
    Anticancer Agents Med Chem, 2021;21(12):1490-1509.
    PMID: 32951580 DOI: 10.2174/1871520620666200918111024
    BACKGROUND: Silver nanoparticles (AgNPs) are among the most investigated nanostructures in recent years, which exhibit more challenging and promising qualities in different biomedical applications. The AgNPs synthesized by the green approach provide potential healthcare benefits over chemical approaches, including improvement of tissue restoration, drug delivery, diagnosis, being environmentally friendly, and a boon to cancer treatment.

    OBJECTIVE: In the current scenario, the development of safe and effective drug delivery systems is the utmost concern of formulation development scientists as well as clinicians.

    METHODS: Google, Web of Science, and PubMed portals have been searched for potentially relevant literature to get the latest developments and updated information related to different aspects of green synthesized AgNPs along with their biomedical applications, especially in the treatment of different types of cancers.

    RESULTS: The present review highlights the latest published research regarding the different green approaches for the synthesis of AgNPs, their characterization techniques as well as various biomedical applications, particularly in cancer treatment. In this context, environment-friendly AgNPs are proving themselves as better candidates in terms of size, drug loading and release efficiency, targeting efficiency, minimal drug-associated side effects, pharmacokinetic profiling, and biocompatibility issues.

    CONCLUSION: With continuous efforts by multidisciplinary team approaches, nanotechnology-based AgNPs will shed new light on diagnostics and therapeutics in various disease treatments. However, the toxicity issues of AgNPs need greater attention as unanticipated toxic effects must be ruled out for their diversified applications.

  4. Microsponge embedded tablet for sustained delivery of nifedipine
    Rahul M, Piyoosh S, Tekade M, Atneriya U, Dua K, Hansbroe PM, et al.
    Pharm Nanotechnol, 2017 09 21.
    PMID: 28933273 DOI: 10.2174/2211738505666170921125549
    BACKGROUND: Nifedipine is a potential therapeutic agent for the treatment of cardiovascular disturbances, although it suffers from short half-life (t1/2, 2 hr).

    OBJECTIVE: To address the problem, we first prepared nifedipine loaded sustained releases microsponges and then formulated tablets for effective clinical application and patient compliance.

    METHOD: Preparations of microsponges were carried out using different composition of nifedipine and polymer (1:1, 1:2 and 1:3 % molar ratio) using emulsion solvent diffusion technique.

    RESULTS: The microsponges with molar ratio 1:3 (formulation code: MF-3) found optimized as revealed by analyzing surface morphology, better powder flow properties (angle of repose; 28.80 ± 0.9, Hausner ratio 1.15 ± 0.2, % compressibility 15.28 ± 0.5% and higher % drug content (80 ± 1.9 %). Different batches of tablets were then formulated incorporating MF-3 microsponges and different proportion (10-50 %) of microcrystalline cellulose and starch as additives. Among tablet formulations, batch composed of 48% of MF-3, 30% of MCC, 20 % of starch and 2 % of talc (TF-33), showed 92.73 ± 2.19 % drug release during 24 hr in vitro release study in comparison to other batches including commercial formulation which was found to be released completely in 20 hr. Further, stability analysis revealed good drug retention of loaded nifedipine as well as consistent in vitro release pattern over a period of 90 days at 40 ºC and 75% RH.

    CONCLUSION: The microsponge tablet delivery system was found to be superior concerning the therapeutic advantage as well as manufacturing feasibility of nifedipine.

  5. Pharmacological Evaluation of the Recuperative Effect of Morusin Against Aluminium Trichloride (AlCl3)-Induced Memory Impairment in Rats
    Gupta G, Chellappan DK, Agarwal M, Ashwathanarayana M, Nammi S, Pabreja K, et al.
    Cent Nerv Syst Agents Med Chem, 2017;17(3):196-200.
    PMID: 27834136 DOI: 10.2174/1871524917666161111095335
    BACKGROUND: Elevation in brain levels of aluminium can be neurotoxic and can cause learning and memory deficiencies. In Chinese medicine, Morus alba is used as a neuroprotective herb. The current study was intended to discover the recuperative effect of morusin against aluminium trichloride (AlCl3)-induced memory impairment in rats along with biochemical mechanism of its protective action.

    METHODS: Memory deficiency was produced by AlCl3 (100 mg/kg; p.o.) in experimental animals. Learning and memory activity was measured using Morris water maze (MWM) test model. Central cholinergic activity was evaluated through the measurement of brain acetylcholinesterase (AChE) activity. In addition to the above, oxidative stress was determined through assessment of brain thiobarbituric acid-reactive species (TBARS) and glutathione (GSH) levels.

    RESULTS: AlCl3 administration prompted significant deficiency of learning and memory in rats, as specified by a noticeable reduction in MWM presentation. AlCl3 administration also produced a significant deterioration in brain AChE action and brain oxidative stress (increase in TBARS and decrease in GSH) levels. Treatment with morusin (5.0 and 10.0 mg/kg, dose orally) significantly overturned AlCl3- induced learning and memory shortages along with diminution of AlCl3-induced rise in brain AChE activity and brain oxidative stress levels.

    CONCLUSION: It may be concluded that morusin exerts a memory-preservative outcome in mental discrepancies of rats feasibly through its various activities.

  6. Fulltext Tumor suppressor role of miR-503
    Gupta G, Chellappan DK, de Jesus Andreoli Pinto T, Hansbro PM, Bebawy M, Dua K
    Panminerva Med, 2018 Mar;60(1):17-24.
    PMID: 29164842 DOI: 10.23736/S0031-0808.17.03386-9
    MicroRNAs (miRNAs) are non-coding RNAs of around 20-25 nucleotides in length with highly conserved characteristics. They moderate post-transcriptional silencing by precisely combining with 3' untranslated regions (UTRs) of target mRNAs at a complementary site. miR‑503, an associate of the "canonical" miRNA-16 family, is expressed in numerous types of tumors such as breast cancer, prostate cancer, lung cancer, colorectal cancer, hepatocellular carcinoma, glioblastoma and several others. There is convincing evidence to show that miR‑503 functions as a tumor suppressor gene through its effects on target genes that regulate cell proliferation, migration, and invasion in tumor cells. In this current assessment, we discuss the biology and tumor suppressor role of miR‑503 in different cancers and elaborate on its mechanism of action.
  7. Novel drug delivery approaches in treating pulmonary fibrosis
    Dua K, Awasthi R, Madan JR, Chellappan DK, Nalluri BN, Gupta G, et al.
    Panminerva Med, 2018 Dec;60(4):238-240.
    PMID: 29480673 DOI: 10.23736/S0031-0808.18.03428-6
  8. Fulltext Advancements in nano drug delivery systems: a challenge for biofilms in respiratory diseases
    Dua K, de Jesus Andreoli Pinto T, Chellappan DK, Gupta G, Bebawy M, Hansbro PM
    Panminerva Med, 2018 03;60(1):35-36.
    PMID: 29370678 DOI: 10.23736/S0031-0808.18.03402-X
  9. Fulltext A clinical update on metformin and lung cancer in diabetic patients
    Gupta G, de Jesus Andreoli Pinto T, Chellappan DK, Mishra A, Malipeddi H, Dua K
    Panminerva Med, 2018 Jun;60(2):70-75.
    PMID: 29370676 DOI: 10.23736/S0031-0808.18.03394-3
    Diabetes mellitus (DM) is frequently increased in many countries and become a serious health problem worldwide. Diabetes is associated with dysfunction of different organs such as heart, eyes, blood vessels, nerves, and kidneys. There is a strong connection between diabetes and cancer. Metformin is one of the most commonly prescribed oral antidiabetic medicines and it is suggested as the first-line therapy due to its comparatively safe, inexpensive, effective and well-tolerated. Some of the in vitro and in vivo investigations proved that metformin may have a direct anticancer action by preventing the proliferation of malignant cells and formations of the colony, inducing arrest of cell cycle and apoptosis and suppressing tumor growth. The antiproliferative mechanism of metformin alone or in combination with various chemotherapeutic agents is complex and involves several beneficial roles. In this regard, clinical studies are required to explain these roles. In the coming future, the use of metformin, alone or in combination with current chemotherapy, might be a conventional approach to effectually manage lung cancer. This mini-review provides a critical overview of currently available clinical trials investigating the effects of metformin in lung cancer.
  10. Formulation and evaluation of niosomal in-situ nasal gel of Buspirone Hydrochloride for brain delivery
    Mathure D, Madan JR, Gujar KN, Tupsamundre A, Ranpise HA, Dua K
    Pharm Nanotechnol, 2018 01 29.
    PMID: 29380709 DOI: 10.2174/2211738506666180130105919
    Considering various merits associated with the nasal mucosa such large surface area, porous endothelial membrane, high blood flow, avoidance of first-pass metabolism, and ready accessibility leads to faster and higher drug absorption. Keeping these facts in mind, the objective of the present study was to develop Buspirone hydrochloride loaded niosomal in-situ nasal gel. Buspirone hydrochloride niosomal in-situ nasal gel was formulated, optimized and evaluated with the aim to deliver drug to the brain via intranasal route. Niosomes were prepared by thin film evaporation method and optimizedusing32 factorial design. The niosomes were characterized for particle size, zeta potential, entrapment efficiency and in-vitro drug release. Buspirone hydrochloride loaded niosomes were further incorporated into Carbopol 934P and HPMC K4M liquid gelling system for formation of in-situ gel. The resultant solution was assessed for various parameters, viz., gelling time, gelling capacity, viscosity at pH 5 and pH 6. Ex-vivo permeation of Buspirone hydrochloride through the sheep nasal mucosa showed that 83.49 % w/w drug permeated after 8 h. The SEM and Zeta potential studies showed formation of good and stable vesicles. Thus, the application of niosomes proved the potential for intranasal drug delivery of Buspirone hydrochloride over the conventional gel formulations. Overall intranasal drug of delivery for Buspirone hydrochloride has been successfully developed.
  11. Nanomedicine and medicinal plants: Emerging symbiosis in managing lung diseases and associated infections
    Paudel KR, De Rubis G, Panth N, Singh SK, Chellappan DK, Hansbro PM, et al.
    EXCLI J, 2022;21:1299-1303.
    PMID: 36483911 DOI: 10.17179/excli2022-5376
  12. Targeting inflammation: a potential approach for the treatment of depression
    Bhatt S, Devadoss T, Jha NK, Baidya M, Gupta G, Chellappan DK, et al.
    Metab Brain Dis, 2023 Jan;38(1):45-59.
    PMID: 36239867 DOI: 10.1007/s11011-022-01095-1
    Major depressive disorder (MDD) or Depression is one of the serious neuropsychiatric disorders affecting over 280 million people worldwide. It is 4th important cause of disability, poor quality of life, and economic burden. Women are more affected with the depression as compared to men and severe depression can lead to suicide. Most of the antidepressants predominantly work through the modulation on the availability of monoaminergic neurotransmitter (NTs) levels in the synapse. Current antidepressants have limited efficacy and tolerability. Moreover, treatment resistant depression (TRD) is one of the main causes for failure of standard marketed antidepressants. Recently, inflammation has also emerged as a crucial factor in pathological progression of depression. Proinflammatory cytokine levels are increased in depressive patients. Antidepressant treatment may attenuate depression via modulation of pathways of inflammation, transformation in structure of brain, and synaptic plasticity. Hence, targeting inflammation may be emerged as an effective approach for the treatment of depression. The present review article will focus on the preclinical and clinical studies that targets inflammation. In addition, it also concentrates on the therapeutic approaches' that targets depression via influence on the inflammatory signaling pathways. Graphical abstract demonstrate the role of various factors in the progression and neuroinflammation, oxidative stress. It also exhibits the association of neuroinflammation, oxidative stress with depression.
  13. Role of Brain-Gut-Microbiota Axis in Depression: Emerging Therapeutic Avenues
    Bhatt S, Kanoujia J, Mohana Lakshmi S, Patil CR, Gupta G, Chellappan DK, et al.
    CNS Neurol Disord Drug Targets, 2023;22(2):276-288.
    PMID: 35352640 DOI: 10.2174/1871527321666220329140804
    The human gut microbiota plays a significant role in the pathophysiology of central nervous system-related diseases. Recent studies suggest correlations between the altered gut microbiota and major depressive disorder (MDD). It is proposed that normalization of the gut microbiota alleviates MDD. The imbalance of brain-gut-microbiota axis also results in dysregulation of the hypothalamicpituitary- adrenal (HPA) axis. This imbalance has a crucial role in the pathogenesis of depression. Treatment strategies with certain antibiotics lead to the depletion of useful microbes and thereby induce depression like effects in subjects. Microbiota is also involved in the synthesis of various neurotransmitters (NTs) like 5-hydroxy tryptamine (5-HT; serotonin), norepinephrine (NE) and dopamine (DA). In addition to NTs, the gut microbiota also has an influence on brain derived neurotrophic factor (BDNF) levels. Recent research findings have exhibited that transfer of stress prone microbiota in mice is also responsible for depression and anxiety-like behaviour in animals. The use of probiotics, prebiotics, synbiotics and proper diet have shown beneficial effects in the regulation of depression pathogenesis. Moreover, transplantation of fecal microbiota from depressed individuals to normal subjects also induces depression-like symptoms. With the precedence of limited therapeutic benefits from monoamine targeting drugs, the regulation of brain-gut microbiota is emerging as a new treatment modality for MDDs. In this review, we elaborate on the significance of brain-gut-microbiota axis in the progression of MDD, particularly focusing on the modulation of the gut microbiota as a mode of treating MDD.
  14. Advancements in nanotherapeutics targeting senescence in chronic obstructive pulmonary disease
    Paudel KR, Mehta M, Shukla SD, Panth N, Chellappan DK, Dua K, et al.
    Nanomedicine (Lond), 2022 Oct;17(23):1757-1760.
    PMID: 35060764 DOI: 10.2217/nnm-2021-0373
  15. The versatility of 18ß-glycyrrhetinic acid in attenuating pulmonary inflammatory disorders
    Mohamad MSB, Reyes RJ, De Rubis G, Paudel KR, Hansbro PM, Dua K, et al.
    EXCLI J, 2023;22:188-190.
    PMID: 36998703 DOI: 10.17179/excli2023-5845
  16. Senolytics: Opening avenues in drug discovery to find novel therapeutics for Parkinson's Disease
    Kakoty V, Kalarikkal Chandran S, Gulati M, Goh BH, Dua K, Kumar Singh S
    Drug Discov Today, 2023 Jun;28(6):103582.
    PMID: 37023942 DOI: 10.1016/j.drudis.2023.103582
    Aging is one of the major risk factors for most neurodegenerative disorders including Parkinson's disease (PD). More than 10 million people are affected with PD worldwide. One of the predominant factors accountable for progression of PD pathology could be enhanced accumulation of senescent cells in the brain with the progress of age. Recent investigations have highlighted that senescent cells can ignite PD pathology via increased oxidative stress and neuroinflammation. Senolytics are agents that kill senescent cells. This review mainly focuses on understanding the pathological connection between senescence and PD, with emphasis on some of the recent advances made in the area of senolytics and their evolution to potential clinical candidates for future pharmaceuticals against PD.
  17. Fulltext Data on known anti-virals in combating CoVid-19
    Akshayaa L, Lakshmi T, Devaraj E, Roy A, Raghunandhakumar S, Sivaperumal P, et al.
    Bioinformation, 2020;16(11):878-881.
    PMID: 34803262 DOI: 10.6026/97320630016878
    Design and development of effective anti-virals in combating CoVid-19 is a great challenge worldwide. Known drugs such as chloroquine, lopinavir, favipiravir and remdesivir are used in the management of CoVid - 19. It is known that Ivermectin and remdesivir both are effective against filoviruses, paramyxo viruses. Available data also shows that ivermectin and remedesivir repress the replication of SARS-CoV-2. Thus, we document the potential use of ivermectin and remdesivir in the management of CoVid -19.
  18. Fulltext Cytotoxic mechanisms of berberine-phytantriol liquid crystalline nanoparticles against non-small-cell lung cancer
    Paudel KR, Manandhar B, Singh SK, Gupta G, Hansbro PM, Chellappan DK, et al.
    EXCLI J, 2023;22:516-519.
    PMID: 37534226 DOI: 10.17179/excli2023-6156
  19. Fulltext Cytotoxic potentials of silibinin assisted silver nanoparticles on human colorectal HT-29 cancer cells
    Jackson K, Devaraj E, Lakshmi T, Rajeshkumar S, Dua K, Chellappan DK, et al.
    Bioinformation, 2020;16(11):817-827.
    PMID: 34803254 DOI: 10.6026/97320630016817
    It is of interest to study the cytotoxicity of silibinin assisted silver nanoparticles in human colorectal (HT-29) cancer cells. Silver nanoparticles were synthesized using silibinin as a reducing agent. The synthesized silibinin assisted silver nanoparticles ( SSNPs) were characterized and analyzed using a transmission electron microscope and spectrophotometer. The SSNPs synthesized in this study are spherical and their size ranges from 10 to 80 nm. HT-29 cells were treated with different concentrations (2, 4, 6, 8 and 10 ng/mL) of SSNPs and cytotoxicity was evaluated. The apoptosis was using flow cytometry. p53 protein expression using western blot. SSNPs are induced a decrease in viability and increased concentration-dependent cytotoxicity in HT-29 cells. SSNPs treatment also caused apoptosis-related morphological changes. SSNPs treatments at 8 and 16 ng/ml showed a prominent apoptotic change i.e., 70.3% and 83.6% respectively, and decreased viability of HT-29 cells 20% and 11.2% respectively as compared to control cells. SSNPs treatments induced p53 expression in HT-29 cells. Data shows that SSNPs have the potential to induce apoptosis in colorectal cancer cells. This provides insights for the further evaluation of SSNPs in fighting colon cancer.
  20. Transform diabetes care with precision medicine
    Kannan S, Chellappan DK, Kow CS, Ramachandram DS, Pandey M, Mayuren J, et al.
    Health Sci Rep, 2023 Nov;6(11):e1642.
    PMID: 37915365 DOI: 10.1002/hsr2.1642
    BACKGROUND AND AIMS: Diabetes is a global concern. This article took a closer look at diabetes and precision medicine.

    METHODS: A literature search of studies related to the use of precision medicine in diabetes care was conducted in various databases (PubMed, Google Scholar, and Scopus).

    RESULTS: Precision medicine encompasses the integration of a wide array of personal data, including clinical, lifestyle, genetic, and various biomarker information. Its goal is to facilitate tailored treatment approaches using contemporary diagnostic and therapeutic techniques that specifically target patients based on their genetic makeup, molecular markers, phenotypic traits, or psychosocial characteristics. This article not only highlights significant advancements but also addresses key challenges, particularly focusing on the technologies that contribute to the realization of personalized and precise diabetes care.

    CONCLUSION: For the successful implementation of precision diabetes medicine, collaboration and coordination among multiple stakeholders are crucial.

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