Displaying publications 1 - 20 of 59 in total

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  1. Epidemiology of Streptococcus pneumoniae infection in Malaysia
    Rohani MY, Raudzah A, Ng AJ, Ng PP, Zaidatul AA, Asmah I, et al.
    Epidemiol Infect, 1999 Feb;122(1):77-82.
    PMID: 10098788
    During a 1-year period from October 1995 to September 1996, 273 isolations of Streptococcus pneumoniae were made from various types of clinical specimens. The majority of the isolates (39.2%) were from sputum whilst 27.5% were from blood, CSF and other body fluids. The organism was isolated from patients of all age groups, 31.1% from children aged 10 years and below, 64.7% of which come from children aged 2 years or below. The majority of the isolates belong to serotypes 1, 6B, 19B, 19F and 23F. Serotypes 1 and 19B were the most common serotypes associated with invasive infection. About 71.9% of the invasive infections were due to serotypes included in the available 23 valent polysaccharide vaccine. The rates of resistance to penicillin and erythromycin were 7.0 and 1.1% respectively. Our findings show that the serotypes of S. pneumoniae causing most invasive infections in Malaysia are similar to those in other parts of the world and the available vaccine may have a useful role in this population.
  2. Caffeic acid phenethyl ester (CAPE) reverses fibrosis caused by chronic colon inflammation in murine model of colitis
    Tambuwala MM, Kesharwani P, Shukla R, Thompson PD, McCarron PA
    Pathol Res Pract, 2018 Nov;214(11):1909-1911.
    PMID: 30170869 DOI: 10.1016/j.prp.2018.08.020
    Fibrosis is known to be the hallmarks of chronic inflammation of the bowel. Epithelial damage due to inflammation compromises the barrier function of the gastrointestinal tract. This barrier dysfunction leads to further spread of inflammation resulting in a chronic state of inflammation. This chronic inflammation leads to development of fibrosis, which has very limited therapeutic options and usually requires surgical removal of the affected tissue. Our previous work has shown that Caffeic acid phenethyl ester (CAPE) is a naturally occurring anti-inflammatory agent, found in propolis, has been found to be protective in experimental colitis via enhancement of epithelial barrier function. However, the impact of CAPE on resolution of fibrosis in the long-term is unknown. The aim of this follow up study was to investigate the effect of CAPE on colon fibrosis in a chronic model of Dextran sulphate sodium induced colitis in mice. Dextran sulphate sodium (DSS) 2.5% w/v was administered in drinking water to induce colitis in C57/BL6 mice for 5 days on the 6th day DSS was stopped and test group mice were treated with intraperitoneal administration of CAPE (30 mg kg-1 day-1) for a further 7 days. Disease activity index (DAI) score, colon length and tissue histology and level of tissue fibrosis was observed. CAPE-treated mice had significantly lower levels of DAI, tissue inflammation scores and fibrosis as compared with control group. Our results show that CAPE is effective in resolving colon fibrosis in chronic inflammation. Thus, we can conclude CAPE could be a potential therapeutic agent for further clinical investigations for treatment of fibrosis in inflammatory bowel diseases in humans.
  3. Antibacterial and antioxidant potential of biosynthesized copper nanoparticles mediated through Cissus arnotiana plant extract
    Rajeshkumar S, Menon S, Venkat Kumar S, Tambuwala MM, Bakshi HA, Mehta M, et al.
    J. Photochem. Photobiol. B, Biol., 2019 Aug;197:111531.
    PMID: 31212244 DOI: 10.1016/j.jphotobiol.2019.111531
    Environment friendly methods for the synthesis of copper nanoparticles have become a valuable trend in the current scenario. The utilization of phytochemicals from plant extracts has become a unique technology for the synthesis of nanoparticles, as they possess dual nature of reducing and capping agents to the nanoparticles. In the present investigation we have synthesized copper nanoparticles (CuNPs) using a rare medicinal plant Cissus arnotiana and evaluated their antibacterial activity against gram negative and gram positive bacteria. The morphology and characterization of the synthesized CuNPs were studied and done using UV-Visible spectroscopy at a wavelength range of 350-380 nm. XRD studies were performed for analyzing the crystalline nature; SEM and TEM for evaluating the spherical shape within the size range of 60-90 nm and AFM was performed to check the surface roughness. The biosynthesized CuNPs showed better antibacterial activity against the gram-negative bacteria, E. coli with an inhibition zone of 22.20 ± 0.16 mm at 75 μg/ml. The antioxidant property observed was comparatively equal with the standard antioxidant agent ascorbic acid at a maximum concentration of 40 μg/ ml. This is the first study reported on C. arnotiana mediated biosynthesis of copper nanoparticles, where we believe that the findings can pave way for a new direction in the field of nanotechnology and nanomedicine where there is a significant potential for antibacterial and antioxidant activities. We predict that, these could lead to an exponential increase in the field of biomedical applications, with the utilization of green synthesized CuNPs, due to its remarkable properties. The highest antibacterial property was observed with gram-negative strains mainly, E. coli, due to its thin peptidoglycan layer and electrostatic interactions between the bacterial cell wall and CuNPs surfaces. Hence, CuNPs can be potent therapeutic agents in several biomedical applications, which are yet to be explored in the near future.
  4. Combinational effect of angiotensin receptor blocker and folic acid therapy on uric acid and creatinine level in hyperhomocysteinemia-associated hypertension
    Singh Y, Samuel VP, Dahiya S, Gupta G, Gillhotra R, Mishra A, et al.
    Biotechnol Appl Biochem, 2019 Sep;66(5):715-719.
    PMID: 31314127 DOI: 10.1002/bab.1799
    Homocysteine [HSCH2 CH2 CH(NH2 )COOH] (Hcy) is a sulfur-containing amino acid of 135.18 Da of molecular weight, generated during conversion of methionine to cysteine. If there is a higher accumulation of Hcy in the blood, that is usually above 15 µmol/L, it leads to a condition referred to as hyperhomocysteinemia. A meta-analysis of observational study suggested an elevated concentration of Hcy in blood, which is termed as the risk factors leading to ischemic heart disease and stroke. Further experimental studies stated that Hcy can lead to an increase in the proliferation of vascular smooth muscle cells and functional impairment of endothelial cells. The analyses confirmed some of the predictors for Hcy presence, such as serum uric acid (UA), systolic blood pressure, and hematocrit. However, angiotensin-converting enzyme inhibitors angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) alone are inadequate for controlling UA and creatinine level, although the addition of folic acid may be beneficial in hypertensive patients who are known to have a high prevalence of elevated Hcy. We hypothesized that combination therapy with an ARB (olmesartan) and folic acid is a promising treatment for lowering the UA and creatinine level in hyperhomocysteinemia-associated hypertension.
  5. The potential of siRNA based drug delivery in respiratory disorders: Recent advances and progress
    Dua K, Wadhwa R, Singhvi G, Rapalli V, Shukla SD, Shastri MD, et al.
    Drug Dev Res, 2019 09;80(6):714-730.
    PMID: 31691339 DOI: 10.1002/ddr.21571
    Lung diseases are the leading cause of mortality worldwide. The currently available therapies are not sufficient, leading to the urgent need for new therapies with sustained anti-inflammatory effects. Small/short or silencing interfering RNA (siRNA) has potential therapeutic implications through post-transcriptional downregulation of the target gene expression. siRNA is essential in gene regulation, so is more favorable over other gene therapies due to its small size, high specificity, potency, and no or low immune response. In chronic respiratory diseases, local and targeted delivery of siRNA is achieved via inhalation. The effectual delivery can be attained by the generation of aerosols via inhalers and nebulizers, which overcomes anatomical barriers, alveolar macrophage clearance and mucociliary clearance. In this review, we discuss the different siRNA nanocarrier systems for chronic respiratory diseases, for safe and effective delivery. siRNA mediated pro-inflammatory gene or miRNA targeting approach can be a useful approach in combating chronic respiratory inflammatory conditions and thus providing sustained drug delivery, reduced therapeutic dose, and improved patient compliance. This review will be of high relevance to the formulation, biological and translational scientists working in the area of respiratory diseases.
  6. Emerging therapeutic potential of the iridoid molecule, asperuloside: A snapshot of its underlying molecular mechanisms
    Chan Y, Ng SW, Xin Tan JZ, Gupta G, Tambuwala MM, Bakshi HA, et al.
    Chem Biol Interact, 2019 Nov 28;315:108911.
    PMID: 31786185 DOI: 10.1016/j.cbi.2019.108911
    Over the years, the attention of researchers in the field of modern drug discovery and development has become further intense on the identification of active compounds from plant sources and traditional remedies, as they exhibit higher therapeutic efficacies and improved toxicological profiles. Among the large diversity of plant extracts that have been discovered and explored for their potential therapeutic benefits, asperuloside, an iridoid glycoside, has been proven to provide promising effects as a therapeutic agent for several diseases. Although, this potent substance exists in several genera, it is primarily found in plants belonging to the genus Eucommia. Recent decades have seen a surge in the research on Asperuloside, making it one of the most studied natural products in the field of medicine and pharmacology. In this review, we have attempted to study the various reported mechanisms of asperuloside that form the basis of its wide spectrum of pharmacological activities.
  7. Fulltext Dynamics of Prolyl Hydroxylases Levels During Disease Progression in Experimental Colitis
    Bakshi HA, Mishra V, Satija S, Mehta M, Hakkim FL, Kesharwani P, et al.
    Inflammation, 2019 Dec;42(6):2032-2036.
    PMID: 31377947 DOI: 10.1007/s10753-019-01065-3
    Hypoxia inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitors are shown to be protective in several models of inflammatory bowel disease (IBD). However, these non-selective inhibitors are known to inhibit all the three isoforms of PHD, i.e. PHD-1, PHD-2 and PHD-3. In the present report, we investigated the associated changes in levels of PHDs during the development and recovery of chemically induced colitis in mice. The results indicated that in the experimental model of murine colitis, levels of both, PHD-1 and PHD-2 were found to be increased with the progression of the disease; however, the level of PHD-3 remained the same in group of healthy controls and mice with colitis. Thus, the findings advocated that inhibitors, which inhibited all three isoforms of PHD could not be ideal therapeutics for IBD since PHD-3 is required for normal gut function. Hence, this necessitates the development of new compounds capable of selectively inhibiting PHD-1 and PHD-2 for effective treatment of IBD.
  8. Central composite designed formulation, characterization and in vitro cytotoxic effect of erlotinib loaded chitosan nanoparticulate system
    Pandey P, Chellappan DK, Tambuwala MM, Bakshi HA, Dua K, Dureja H
    Int J Biol Macromol, 2019 Dec 01;141:596-610.
    PMID: 31494160 DOI: 10.1016/j.ijbiomac.2019.09.023
    The most common cause of deaths due to cancers nowadays is lung cancer. The objective of this study was to prepare erlotinib loaded chitosan nanoparticles for their anticancer potential. To study the effect of formulation variables on prepared nanoparticles using central composite design. Erlotinib loaded chitosan nanoparticles were prepared by ionic gelation method using probe sonication technique. It was found that batch NP-7 has a maximum loading capacity and entrapment efficiency with a particle size (138.5 nm) which is ideal for targeting solid tumors. Analysis of variance was applied to the particle size, entrapment efficiency and percent cumulative drug release to study the fitting and the significance of the model. The batch NP-7 showed 91.57% and 39.78% drug release after 24 h in 0.1 N hydrochloric acid and Phosphate Buffer (PB) pH 6.8, respectively. The IC50 value of NP-7 evaluated on A549 Lung cancer cells was found to be 6.36 μM. The XRD of NP-7 displayed the existence of erlotinib in the amorphous pattern. The optimized batch released erlotinib slowly in comparison to the marketed tablet formulation. Erlotinib loaded chitosan nanoparticles were prepared successfully using sonication technique with suitable particle size, entrapment efficiency and drug release. The formulated nanoparticles can be utilized for the treatment of lung cancer.
  9. Emerging Complexity and the Need for Advanced Drug Delivery in Targeting Candida Species
    Wadhwa R, Pandey P, Gupta G, Aggarwal T, Kumar N, Mehta M, et al.
    Curr Top Med Chem, 2019;19(28):2593-2609.
    PMID: 31746290 DOI: 10.2174/1568026619666191026105308
    BACKGROUND: Candida species are the important etiologic agents for candidiasis, the most prevalent cause of opportunistic fungal infections. Candida invasion results in mucosal to systemic infections through immune dysfunction and helps in further invasion and proliferation at several sites in the host. The host defence system utilizes a wide array of the cells, proteins and chemical signals that are distributed in blood and tissues which further constitute the innate and adaptive immune system. The lack of antifungal agents and their limited therapeutic effects have led to high mortality and morbidity related to such infections.

    METHODS: The necessary information collated on this review has been gathered from various literature published from 1995 to 2019.

    RESULTS: This article sheds light on novel drug delivery approaches to target the immunological axis for several Candida species (C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. rugose, C. hemulonii, etc.).

    CONCLUSION: It is clear that the novel drug delivery approaches include vaccines, adoptive transfer of primed immune cells, recombinant cytokines, therapeutic antibodies, and nanoparticles, which have immunomodulatory effects. Such advancements in targeting various underpinning mechanisms using the concept of novel drug delivery will provide a new dimension to the fungal infection clinic particularly due to Candida species with improved patient compliance and lesser side effects. This advancement in knowledge can also be extended to target various other similar microbial species and infections.

  10. Monotherapy of RAAS blockers and mobilization of aldosterone: A mechanistic perspective study in kidney disease
    Gupta G, Dahiya R, Singh Y, Mishra A, Verma A, Gothwal SK, et al.
    Chem Biol Interact, 2020 Feb 01;317:108975.
    PMID: 32032593 DOI: 10.1016/j.cbi.2020.108975
    In patients with acute kidney injury progressively converting into chronic kidney disease (CKD), proteinuria and high blood pressure predict progression to end-stage renal disease (ESRD). Although, Renin-angiotensin-aldosterone system (RAAS) regulates blood pressure and kidney disease through both direct and indirect mechanisms. RAAS blockers that act at the level of angiotensin or lower in the cascade can cause compensatory increases in the plasma renin and angiotensin II level. Here, in this review article, we are exploring the evidence-based on RAAS blockade action releases of aldosterone and hypothesizing the molecular mechanism for converting the acute kidney injury into chronic kidney disease to end-stage renal disease.
  11. Immunological axis of berberine in managing inflammation underlying chronic respiratory inflammatory diseases
    Tew XN, Xin Lau NJ, Chellappan DK, Madheswaran T, Zeeshan F, Tambuwala MM, et al.
    Chem Biol Interact, 2020 Feb 01;317:108947.
    PMID: 31968208 DOI: 10.1016/j.cbi.2020.108947
    Inflammatory responses play a remarkable role in the mechanisms of acute and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis and lung cancer. Currently, there is a resurgence in the use of drugs from natural sources for various ailments as potent therapeutics. Berberine, an alkaloid prominent in the Chinese traditional system of medicine has been reported to exert therapeutic properties in various diseases. Nevertheless, the number of studies focusing on the curative potential of berberine in inflammatory diseases involving the respiratory system is limited. In this review, we have attempted to discuss the reported anti-inflammatory properties of berberine that function through several pathways such as, the NF-κB, ERK1/2 and p38 MAPK pathways which affect several pro-inflammatory cytokines in the pathophysiological processes involved in chronic respiratory diseases. This review would serve to provide valuable information to researchers who work in this field and a new direction in the field of drug discovery with respect to respiratory diseases.
  12. Molecular signaling of G-protein-coupled receptor in chronic heart failure and associated complications
    Altamish M, Samuel VP, Dahiya R, Singh Y, Deb PK, Bakshi HA, et al.
    Drug Dev Res, 2020 02;81(1):23-31.
    PMID: 31785110 DOI: 10.1002/ddr.21627
    The well-known condition of heart failure is a clinical syndrome that results when the myocardium's ability to pump enough blood to meet the body's metabolic needs is impaired. Most of the cardiac activity is maintained by adrenoceptors, are categorized into two main α and β and three distinct subtypes of β receptor: β1-, β2-, and β3-adrenoceptors. The β adrenoreceptor is the main regulatory macro proteins, predominantly available on heart and responsible for down regulatory cardiac signaling. Moreover, the pathological involvement of Angiotensin-converting enzyme 1 (ACE1)/angiotensin II (Ang II)/angiotensin II type 1 (AT1) axis and beneficial ACE2/Ang (1-7)/Mas receptor axis also shows protective role via Gi βγ, during heart failure these receptors get desensitized or internalized due to increase in the activity of G-protein-coupled receptor kinase 2 (GRK2) and GRK5, responsible for phosphorylation of G-protein-mediated down regulatory signaling. Here, we investigate the various clinical and preclinical data that exhibit the molecular mechanism of upset level of GRK change the cardiac activity during failing heart.
  13. Fulltext Gold nanoparticles attenuate albuminuria by inhibiting podocyte injury in a rat model of diabetic nephropathy
    Alomari G, Al-Trad B, Hamdan S, Aljabali A, Al-Zoubi M, Bataineh N, et al.
    Drug Deliv Transl Res, 2020 Feb;10(1):216-226.
    PMID: 31637677 DOI: 10.1007/s13346-019-00675-6
    Several recent studies have reported that gold nanoparticles (AuNPs) attenuate hyperglycemia in diabetic animal models without any observed side effects. The present study was intended to provide insight into the effects of 50-nm AuNPs on diabetic kidney disease. Adult male rats were divided into three groups (n = 7/group): control (non-diabetic, ND), diabetic (D), and diabetic treated intraperitoneally with 50-nm AuNPs (AuNPs + D; 2.5 mg/kg/day) for 7 weeks. Diabetes was induced by a single-dose injection of 55 mg/kg streptozotocin. The result showed that AuNP treatment prevented diabetes-associated increases in the blood glucose level. Reduction in 24-h urinary albumin excretion rate, glomerular basement membrane thickness, foot process width, and renal oxidative stress markers was also demonstrated in the AuNP-treated group. In addition, the results showed downregulation effect of AuNPs in renal mRNA or protein expression of transforming growth factor β1 (TGF-β1), fibronectin, collagen IV, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor-A (VEGF-A). Moreover, the protein expression of nephrin and podocin, podocyte markers, in glomeruli was increased in the AuNPs + D group compared with the D group. These results provide evidence that 50-nm AuNPs can ameliorate renal damage in experimental models of diabetic nephropathy through improving the renal function and downregulating extracellular matrix protein accumulation, along with inhibiting renal oxidative stress and amelioration of podocyte injury.
  14. Nanocarriers: more than tour de force for thymoquinone
    Rathore C, Rathbone MJ, Chellappan DK, Tambuwala MM, Pinto TJA, Dureja H, et al.
    Expert Opin Drug Deliv, 2020 04;17(4):479-494.
    PMID: 32077770 DOI: 10.1080/17425247.2020.1730808
    Introduction: Thymoquinone (TQ), 2-isopropyl-5-methylbenzo-1, 4-quinone, the main active constituent of Nigella sativa (NS) plant, has been proven to be of great therapeutic aid in various in vitro and in vivo conditions. Despite the promising therapeutic activities of TQ, this molecule is not yet in the clinical trials, restricted by its poor biopharmaceutical properties including photo-instability.Area covered: This review compiles the different types of polymeric and lipidic nanocarriers (NCs), encapsulating TQ for their improved oral bioavailability, and augmented in vitro and in vivo efficacy, evidenced on various pathologies. Furthermore, we provide a comprehensive overview of TQ in relation to its encapsulation approaches advancing the delivery and improving the efficacy of TQ.Expert opinion: TQ was first identified in the essential oil of Nigella sativa L. black seed. TQ has not been used in formulations because it is a highly hydrophobic drug having poor aqueous solubility. To deal with the poor physicochemical problems associated with TQ, various NCs encapsulating TQ have been tried in the past. Nevertheless, these NCs could be impending in bringing forth this potential molecule to clinical reality. This will also be beneficial for a large research community including pharmaceutical & biological sciences and translational researchers.
  15. Targeting neutrophils using novel drug delivery systems in chronic respiratory diseases
    Chellappan DK, Yee LW, Xuan KY, Kunalan K, Rou LC, Jean LS, et al.
    Drug Dev Res, 2020 06;81(4):419-436.
    PMID: 32048757 DOI: 10.1002/ddr.21648
    Neutrophils are essential effector cells of immune system for clearing the extracellular pathogens during inflammation and immune reactions. Neutrophils play a major role in chronic respiratory diseases. In respiratory diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, lung cancer and others, there occurs extreme infiltration and activation of neutrophils followed by a cascade of events like oxidative stress and dysregulated cellular proteins that eventually result in apoptosis and tissue damage. Dysregulation of neutrophil effector functions including delayed neutropil apoptosis, increased neutrophil extracellular traps in the pathogenesis of asthma, and chronic obstructive pulmonary disease enable neutrophils as a potential therapeutic target. Accounting to their role in pathogenesis, neutrophils present as an excellent therapeutic target for the treatment of chronic respiratory diseases. This review highlights the current status and the emerging trends in novel drug delivery systems such as nanoparticles, liposomes, microspheres, and other newer nanosystems that can target neutrophils and their molecular pathways, in the airways against infections, inflammation, and cancer. These drug delivery systems are promising in providing sustained drug delivery, reduced therapeutic dose, improved patient compliance, and reduced drug toxicity. In addition, the review also discusses emerging strategies and the future perspectives in neutrophil-based therapy.
  16. Fulltext Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage
    Bakshi HA, Zoubi MSA, Hakkim FL, Aljabali AAA, Rabi FA, Hafiz AA, et al.
    Nutrients, 2020 06 26;12(6).
    PMID: 32604971 DOI: 10.3390/nu12061901
    Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.
  17. Fulltext Plants derived therapeutic strategies targeting chronic respiratory diseases: Chemical and immunological perspective
    Prasher P, Sharma M, Mehta M, Paudel KR, Satija S, Chellappan DK, et al.
    Chem Biol Interact, 2020 Jul 01;325:109125.
    PMID: 32376238 DOI: 10.1016/j.cbi.2020.109125
    The apparent predicament of the representative chemotherapy for managing respiratory distress calls for an obligatory deliberation for identifying the pharmaceuticals that effectively counter the contemporary intricacies associated with target disease. Multiple, complex regulatory pathways manifest chronic pulmonary disorders, which require chemotherapeutics that produce composite inhibitory effect. The cost effective natural product based molecules hold a high fervor to meet the prospects posed by current respiratory-distress therapy by sparing the tedious drug design and development archetypes, present a robust standing for the possible replacement of the fading practice of poly-pharmacology, and ensure the subversion of a potential disease relapse. This study summarizes the experimental evidences on natural products moieties and their components that illustrates therapeutic efficacy on respiratory disorders.
  18. Molecular mechanisms of action of naringenin in chronic airway diseases
    Chin LH, Hon CM, Chellappan DK, Chellian J, Madheswaran T, Zeeshan F, et al.
    Eur J Pharmacol, 2020 Jul 15;879:173139.
    PMID: 32343971 DOI: 10.1016/j.ejphar.2020.173139
    Chronic airway inflammatory diseases are characterized by persistent proinflammatory responses in the respiratory tract. Although, several treatment strategies are currently available, lifelong therapy is necessary for most of these diseases. In recent years, phytophenols, namely, flavonoids, derived from fruits and vegetables have been gaining tremendous interest and have been extensively studied due to their low toxicological profile. Naringenin is a bioflavonoid abundantly found in citrus fruits. This substance has shown notable therapeutic potential in various diseases due to its promising diverse biological activities. In this review, we have attempted to review the published studies from the available literature, discussing the molecular level mechanisms of naringenin in different experimental models of airway inflammatory diseases including asthma, chronic obstructive pulmonary disease (COPD), lung cancer, pulmonary fibrosis and cystic fibrosis. Current evidences have proposed that the anti-inflammatory properties of naringenin play a major role in ameliorating inflammatory disease states. In addition, naringenin also possesses several other biological properties. Despite the proposed mechanisms suggesting remarkable therapeutic benefits, the clinical use of naringenin is, however, hampered by its low solubility and bioavailability. Furthermore, this review also discusses on the studies that utilise nanocarriers as a drug delivery system to address the issue of poor solubility.
  19. Probing 3CL protease: Rationally designed chemical moieties for COVID-19
    Sharma M, Prasher P, Mehta M, Zacconi FC, Singh Y, Kapoor DN, et al.
    Drug Dev Res, 2020 Jul 30.
    PMID: 32729640 DOI: 10.1002/ddr.21724
  20. Cellular signalling pathways mediating the pathogenesis of chronic inflammatory respiratory diseases: an update
    Mehta M, Dhanjal DS, Paudel KR, Singh B, Gupta G, Rajeshkumar S, et al.
    Inflammopharmacology, 2020 Aug;28(4):795-817.
    PMID: 32189104 DOI: 10.1007/s10787-020-00698-3
    Respiratory disorders, especially non-communicable, chronic inflammatory diseases, are amongst the leading causes of mortality and morbidity worldwide. Respiratory diseases involve multiple pulmonary components, including airways and lungs that lead to their abnormal physiological functioning. Several signaling pathways have been reported to play an important role in the pathophysiology of respiratory diseases. These pathways, in addition, become the compounding factors contributing to the clinical outcomes in respiratory diseases. A range of signaling components such as Notch, Hedgehog, Wingless/Wnt, bone morphogenetic proteins, epidermal growth factor and fibroblast growth factor is primarily employed by these pathways in the eventual cascade of events. The different aberrations in such cell-signaling processes trigger the onset of respiratory diseases making the conventional therapeutic modalities ineffective. These challenges have prompted us to explore novel and effective approaches for the prevention and/or treatment of respiratory diseases. In this review, we have attempted to deliberate on the current literature describing the role of major cell signaling pathways in the pathogenesis of pulmonary diseases and discuss promising advances in the field of therapeutics that could lead to novel clinical therapies capable of preventing or reversing pulmonary vascular pathology in such patients.
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