Deciphering the Association of Epstein-Barr Virus and Its Glycoprotein M Peptide with Neuropathologies in Mice.

The reactivation of ubiquitously present Epstein-Barr virus (EBV) is known to be involved with numerous diseases, including neurological ailments. A recent in vitro study from our group unveiled the association of EBV and its 12-amino acid peptide glycoprotein M146-157 (gM146-157) with neurodegenerative diseases, viz., Alzheimer's disease (AD) and multiple sclerosis. In this study, we have further validated this association at the in vivo level. The exposure of EBV/gM146-157 to mice causes a decline in the cognitive ability with a concomitant increase in anxiety-like symptoms through behavioral assays. Disorganization of hippocampal neurons, cell shrinkage, pyknosis, and apoptotic appendages were observed in the brains of infected mice. Inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were found to be elevated in infected mouse brain tissue samples, whereas TNF-α exhibited a decline in the serum of these mice. Further, the altered levels of nuclear factor-kappa B (NF-kB) and neurotensin receptor 2 affirmed neuroinflammation in infected mouse brain samples. Similarly, the risk factor of AD, apolipoprotein E4 (ApoE4), was also found to be elevated at the protein level in EBV/gM146-157 challenged mice. Furthermore, we also observed an increased level of myelin basic protein in the brain cortex. Altogether, our results suggested an integral connection of EBV and its gM146-157 peptide to the neuropathologies.

SARS-CoV-2 envelope protein induces necroptosis and mediates inflammatory response in lung and colon cells through receptor interacting protein kinase 1.

SARS-CoV-2 Envelope protein (E) is one of the crucial components in virus assembly and pathogenesis. The current study investigated its role in the SARS-CoV-2-mediated cell death and inflammation in lung and gastrointestinal epithelium and its effect on the gastrointestinal-lung axis. We observed that transfection of E protein increases the lysosomal pH and induces inflammation in the cell. The study utilizing Ethidium bromide/Acridine orange and Hoechst/Propidium iodide staining demonstrated necrotic cell death in E protein transfected cells. Our study revealed the role of the necroptotic marker RIPK1 in cell death. Additionally, inhibition of RIPK1 by its specific inhibitor Nec-1s exhibits recovery from cell death and inflammation manifested by reduced phosphorylation of NFκB. The E-transfected cells' conditioned media induced inflammation with differential expression of inflammatory markers compared to direct transfection in the gastrointestinal-lung axis. In conclusion, SARS-CoV-2 E mediates inflammation and necroptosis through RIPK1, and the E-expressing cells' secretion can modulate the gastrointestinal-lung axis. Based on the data of the present study, we believe that during severe COVID-19, necroptosis is an alternate mechanism of cell death besides ferroptosis, especially when the disease is not associated with drastic increase in serum ferritin.

Redefining Lobe-Wise Ground-Glass Opacity in COVID-19 Through Deep Learning and its Correlation With Biochemical Parameters.

During COVID-19 pandemic qRT-PCR, CT scans and biochemical parameters were studied to understand the patients' physiological changes and disease progression. There is a lack of clear understanding of the correlation of lung inflammation with biochemical parameters available. Among the 1136 patients studied, C-reactive-protein (CRP) is the most critical parameter for classifying symptomatic and asymptomatic groups. Elevated CRP is corroborated with increased D-dimer, Gamma-glutamyl-transferase (GGT), and urea levels in COVID-19 patients. To overcome the limitations of manual chest CT scoring system, we segmented the lungs and detected ground-glass-opacity (GGO) in specific lobes from 2D CT images by 2D U-Net-based deep learning (DL) approach. Our method shows accuracy, compared to the manual method (  âˆ¼ 80%), which is subjected to the radiologist's experience. We determined a positive correlation of GGO in the right upper-middle (0.34) and lower (0.26) lobe with D-dimer. However, a modest correlation was observed with CRP, ferritin and other studied parameters. The final Dice Coefficient (or the F1 score) and Intersection-Over-Union for testing accuracy are 95.44% and 91.95%, respectively. This study can help reduce the burden and manual bias besides increasing the accuracy of GGO scoring. Further study on geographically diverse large populations may help to understand the association of the biochemical parameters and pattern of GGO in lung lobes with different SARS-CoV-2 Variants of Concern's disease pathogenesis in these populations.

Outer Membrane Vesicles: An Emerging Vaccine Platform.

Vaccine adjuvants are substances that improve the immune capacity of a recombinant vaccine to a great extent and have been in use since the early 1900s; they are primarily short-lived and initiate antigen activity, mainly an inflammatory response. With the developing technologies and innovation, early options such as alum were modified, yet the inorganic nature of major vaccine adjuvants caused several side effects. Outer membrane vesicles, which respond to the stressed environment, are small nano-sized particles secreted by gram-negative bacteria. The secretory nature of OMV gives us many benefits in terms of infection bioengineering. This article aims to provide a detailed overview of bacteria's outer membrane vesicles (OMV) and their potential usage as adjuvants in making OMV-based vaccines. The OMV adjuvant-based vaccines can be a great benefactor, and there are ongoing trials for formulating OMV adjuvant-based vaccines for SARS-CoV-2. This study emphasizes engineering the OMVs to develop better versions for safety purposes. This article will also provide a gist about the advantages and disadvantages of such vaccines, along with other aspects.

Anti-cancer Effects of 5-Aminoimidazole-4-Carboxamide-1-ß-D-Ribofuranoside (AICAR) on Triple-negative Breast Cancer (TNBC) Cells: Mitochondrial Modulation as an Underlying Mechanism.

BACKGROUND: Triple-negative breast cancer (TNBC) is known for Warburg effect and defects in the mitochondria. AMP-dependent kinase (AMPK) activates the downstream transcription factors PGC-1α, PGC-1ß, or FOXO1, which participate in mitochondrial biogenesis. 5- aminoimidazole-4-carboxamide riboside (AICAR) is an analog of adenosine monophosphate and is a direct activator of AMPK. OBJECTIVES: In the present study, we have made an attempt to understand the influence of AICAR on TNBC cells, MDA-MB-231, and the underlying changes in mitochondrial biogenesis, if any. METHODS: We investigated AICAR induced changes in cell viability, apoptosis, migratory potential, and changes in the sensitivity of doxorubicin. RESULTS: In response to the treatment of MDA-MB-231 breast cancer cells with 750 µM of AICAR for 72 hours, followed by 48 hours in fresh media without AICAR, we observed a decrease in viability via MTT assay, reduction in cell numbers along with the apoptotic appearance, increased cell death by ELISA, decreased lactate in conditioned medium and decrease in migration by scratch and transwell migration assays. These changes in the cancer phenotype were accompanied by an increase in mitochondrial biogenesis, as observed by increased mitochondrial DNA to nuclear DNA ratio, a decrease in lactic acid concentration, an increase in MitoTracker green and red staining, and increased expression of transcription factors PGC-1α, NRF-1, NRF-2, and TFAM, contributing to mitochondrial biogenesis. Pre-treatment of cells with AICAR for 72 hours followed by 48 hours treatment with 1 µM doxorubicin showed an increased sensitivity to doxorubicin as assessed by the MTT assay. CONCLUSION: Our results show that AICAR exerts beneficial effects on TNBC cells, possibly via switching off the Warburg effect and switching on the anti-Warburg effect through mitochondrial modulation.

Potential entry receptors for human γ-herpesvirus into epithelial cells: A plausible therapeutic target for viral infections.

Herpesviruses are ubiquitous viruses, specifically the Epstein Barr virus (EBV). EBV and Kaposi's sarcoma-associated herpesvirus (KSHV) establish their latency for a long period in B-cells and their reactivation instigates dreadful diseases from cancer to neurological modalities. The envelope glycoprotein of these viruses makes an attachment with several host receptors. For instance; glycoprotein 350/220, gp42, gHgL and gB of EBV establish an attachment with CD21, HLA-DR, Ephs, and other receptor molecules to hijack the B- and epithelial cell machinery. Ephs are reported recently as potent receptors for EBV entry into epithelial cells. Eph receptors play a role in the maintenance and control of various cellular processes including morphology, adhesion, proliferation, survival and differentiation. Alterations in the structure and expression of Eph and ephrin (Eph ligands) molecules is entangled with various pathologies including tumours and neurological complications. Along with Eph, integrins, NRP, NMHC are also key players in viral infections as they are possibly involved in viral transmission, replication and persistence. Contrarily, KSHV gH is known to interact with EphA2 and -A4 molecules, whereas in the case of EBV only EphA2 receptors are being reported to date. The ELEFN region of KSHV gH was involved in the interaction with EphA2, however, the interacting region of EBV gH is elusive. Further, the gHgL of KSHV and EBV form a complex with the EphA2 ligand-binding domain (LBD). Primarily by using gL both KSHV and EBV gHgL bind to the peripheral regions of LBD. In addition to γ-herpesviruses, several other viruses like Nipah virus, Cedar virus, Hepatitis C virus and Rhesus macaque rhadinovirus (RRV) also access the host cells via Eph receptors. Therefore, we summarise the possible roles of Eph and ephrins in virus-mediated infection and these molecules could serve as potential therapeutic targets.

Therapeutically effective covalent spike protein inhibitors in treatment of SARS-CoV-2.

COVID-19 [coronavirus disease 2019] has resulted in over 204,644,849 confirmed cases and over 4,323,139 deaths throughout the world as of 12 August 2021, a total of 4,428,168,759 vaccine doses have been administered. The lack of potentially effective drugs against the virus is making the situation worse and dangerous. Numerous forces are working on finding an effective treatment against the virus but it is believed that a de novo drug would take several months even if huge financial support is provided. The only solution left with is drug repurposing that would not only provide effective therapy with the already used clinical drugs, but also save time and cost of the de novo drug discovery. The initiation of the COVID-19 infection starts with the attachment of spike glycoprotein of SARS-CoV-2 to the host receptor. Hence, the inhibition of the binding of the virus to the host membrane and the entry of the viral particle into the host cell are one of the main therapeutic targets. This paper not only summarizes the structure and the mechanism of spike protein, but the main focus is on the potential covalent spike protein inhibitors.

Complex Interplay of Genes Underlies Invasiveness in Fibrosarcoma Progression Model.

Sarcomas are a heterogeneous group of mesenchymal tumours, with a great variability in their clinical behaviour. While our knowledge of sarcoma initiation has advanced rapidly in recent years, relatively little is known about mechanisms of sarcoma progression. JUN-murine fibrosarcoma progression series consists of four sarcoma cell lines, JUN-1, JUN-2, JUN-2fos-3, and JUN-3. JUN-1 and -2 were established from a single tumour initiated in a H2K/v-jun transgenic mouse, JUN-3 originates from a different tumour in the same animal, and JUN-2fos-3 results from a targeted in vitro transformation of the JUN-2 cell line. The JUN-1, -2, and -3 cell lines represent a linear progression from the least transformed JUN-2 to the most transformed JUN-3, with regard to all the transformation characteristics studied, while the JUN-2fos-3 cell line exhibits a unique transformation mode, with little deregulation of cell growth and proliferation, but pronounced motility and invasiveness. The invasive sarcoma sublines JUN-2fos-3 and JUN-3 show complex metabolic profiles, with activation of both mitochondrial oxidative phosphorylation and glycolysis and a significant increase in spared respiratory capacity. The specific transcriptomic profile of invasive sublines features very complex biological relationships across the identified genes and proteins, with accentuated autocrine control of motility and angiogenesis. Pharmacologic inhibition of one of the autocrine motility factors identified, Ccl8, significantly diminished both motility and invasiveness of the highly transformed fibrosarcoma cell. This progression series could be greatly valuable for deciphering crucial aspects of sarcoma progression and defining new prognostic markers and potential therapeutic targets.

Cross Talk between COVID-19 and Breast Cancer.

Cancer patients are more susceptible to COVID-19; however, the prevalence of COVID-19 in different types of cancer is still inconsistent and inconclusive. Here, we delineate the intricate relationship between breast cancer and COVID-19. Breast cancer and COVID-19 share the involvement of common comorbidities, hormonal signalling pathways, gender differences, rennin- angiotensin system (RAS), angiotensin-converting enzyme-2 (ACE-2), transmembrane protease serine 2 (TMPRSS2) and dipeptidyl peptidase-IV (DPP-IV). We also shed light on the possible effects of therapeutic modalities of COVID-19 on breast cancer outcomes. Briefly, we conclude that breast cancer patients are more susceptible to COVID-19 in comparison with their normal counterparts. Women are more resistant to the occurrence and severity of COVID-19. Increased expressions of ACE2 and TMPRSS2 are correlated with occurrence and severity of COVID-19, but higher expression of ACE2 and lower expression of TMPRSS2 are prognostic markers for overall disease free survival in breast cancer. The ACE2 inhibitors and ibuprofen therapies for COVID-19 treatment may aggravate the clinical condition of breast cancer patients through chemo-resistance and metastasis. Most of the available therapeutic modalities for COVID-19 were also found to exert positive effects on breast cancer outcomes. Besides drugs in clinical trend, TMPRSS2 inhibitors, estrogen supplementation, androgen deprivation and DPP-IV inhibitors may also be used to treat breast cancer patients infected with SARS-CoV-2. However, drug-drug interactions suggest that some of the drugs used for the treatment of COVID-19 may modulate the drug metabolism of anticancer therapies which may lead to adverse drug reaction events.

Potential of algal metabolites for the development of broad-spectrum antiviral therapeutics: Possible implications in COVID-19 therapy.

Covid-19 pandemic severely affected human health worldwide. Till October 19, 2020, total confirmed patients of COVID-19 are 39,944,882, whereas 1,111,998 people died across the globe. Till to date, we do not have any specific medicine and/or vaccine to treat COVID-19; however, research is still going on at war footing. So far vaccine development is concerned, here it is noteworthy that till now three major variants (named A, B, and C) of severe acute respiratory syndrome-coronavirus2 (SARS-CoV-2) have been recognized. Increased mutational rate and formation of new viral variants may increase the attrition rate of vaccines and/or candidate chemotherapies. Herbal remedies are chemical cocktails, thus open another avenue for effective antiviral therapeutics development. In fact, India is a large country, which is densely populated, but the overall severity of COVID-19 per million populations is lesser than any other country of the world. One of the major reasons for the aforesaid difference is the use of herbal remedies by the Government of India as a preventive measure for COVID-19. Therefore, the present review focuses on the epidemiology and molecular pathogenesis of COVID-19 and explores algal metabolites for their antiviral properties.

Urothelial Cancer Stem Cell Heterogeneity.

Urothelial carcinoma is a tumor type featuring pronounced intertumoral heterogeneity and a high mutational and epigenetic load. The two major histopathological urothelial carcinoma types - the non-muscle-invasive and muscle-invasive urothelial carcinoma - markedly differ in terms of their respective typical mutational profiles and also by their probable cells of origin, that is, a urothelial basal cell for muscle-invasive carcinomas and a urothelial intermediate cell for at least a large part of non-muscle-invasive carcinomas. Both non-muscle-invasive and muscle-invasive urothelial carcinomas can be further classified into discrete intrinsic subtypes based on their typical transcriptomic profiles. Urothelial carcinogenesis shows a number of parallels to a urothelial regenerative response. Both of these processes seem to be dominated by specific stem cell populations. In the last years, the nature and location of urothelial stem cell(s) have been subject to many controversies, which now seem to be settled down, favoring the existence of a largely single urothelial stem cell type located among basal cells. Basal cell markers have also been amply used to identify urothelial carcinoma stem cells, especially in muscle-invasive disease, but they proved useful even in some non-muscle-invasive tumors. Analyses on molecular nature of urothelial carcinoma stem cells performed till now point to their great heterogeneity, both during the tumor development and upon intertumoral comparison, sexual dimorphism providing a special example of the latter. Moreover, urothelial cancer stem cells are endowed with intrinsic plasticity, whereby they can modulate their stemness in relation to other tumor-related traits, especially motility and invasiveness. Such transitional modulations suggest underlying epigenetic mechanisms and, even within this context, inter- and intratumoral heterogeneity becomes apparent. Multiple molecular aspects of urothelial cancer stem cell biology markedly influence therapeutic response, implying their knowledge as a prerequisite to improved therapies of this disease. At the same time, the notion of urothelial cancer stem cell heterogeneity implies that this therapeutic benefit would be most probably and most efficiently achieved within the context of individualized antitumor therapy.

Urothelial Carcinoma Stem Cells: Current Concepts, Controversies, and Methods.

Cancer stem cells are defined as a self-renewing and self-protecting subpopulation of cancer cells able to differentiate into morphologically and functionally diverse cancer cells with a limited lifespan. To purify cancer stem cells, two basic approaches can be applied, the marker-based approach employing various more of less-specific cell surface marker molecules and a marker-free approach largely based on various self-protection mechanisms. Within the context of urothelial carcinoma, both methods could find use. The cell surface markers have been mainly derived from the urothelial basal cell, a probable cell of origin of muscle-invasive urothelial carcinoma, with CD14, CD44, CD90, and 67LR representing successful examples of this strategy. The marker-free approaches involve side population sorting, for which a detailed protocol is provided, as well as the Aldefluor assay, which rely on a specific overexpression of efflux pumps or the detoxification enzyme aldehyde dehydrogenase, respectively, in stem cells. These assays have been applied to both non-muscle-invasive and muscle-invasive bladder cancer samples and cell lines. Urothelial carcinoma stem cells feature a pronounced heterogeneity as to their molecular stemness mechanisms. Several aspects of urothelial cancer stem cell biology could enter translational development rather soon, e.g., a specific CD44+-derived gene expression signature able to identify non-muscle-invasive bladder cancer patients with a high risk of progression, or deciphering a mechanism responsible for repopulating activity of urothelial carcinoma stem cells within the context of therapeutic resistance.

Protective Effect of Aspirin Against Oligomeric Aß42 Induced Mitochondrial Alterations and Neurotoxicity in Differentiated EC P19 Neuronal Cells.

BACKGROUND: Amyloid-beta (Aß) induced mitochondrial dysfunction is one of the major causes of neuronal toxicity in Alzheimer's disease. A number of recent reports suggest involvement of mitochondrial alterations through intracellular accumulation of oligomeric Aß. These mitochondrial alterations include increased Reactive Oxygen Species (ROS), mt-DNA depletion, decreased oxidative phosphorylation and ATP production, membrane depolarization, reduced number of mitochondria etc. All these defects cumulatively caused neural toxicity and alterations in cellular energy homeostasis. On the other hand, anti-inflammatory drug aspirin is reported to promote both mitochondrial biogenesis and improvement in cellular energy status. METHODS: Taking altogether the mentioned clues, we evaluated protective effect of aspirin, if any on oligomeric Aß42 induced toxicity and mitochondrial alterations in differentiated neuronal cells. RESULTS: A significant reduction in neuronal viability and increased apoptosis was observed in Aß42 treated cells, as evident by MTT assay, apoptosis ELISA and immunofluorescence from ß-III tubulin antibody staining of neuronal cells. A concomitant decrease was also observed in the intensity of mitotracker red FM staining and mt-DNA to nDNA ratio, suggesting mitochondrial membrane depolarization and/or reduced number of mitochondria along with depletion in mt-DNA. However, simultaneous treatment of 5 µM aspirin to oligomeric Aß42 treated cells protected them from mitochondrial dysfunction and neurotoxicity. CONCLUSION: We suggest mitochondrial biogenesis, changes in mitochondrial membrane potential and / or inhibition of Aß42 aggregation by aspirin as possible underlying mechanism(s).

Anti-Inflammatory Role of Thyroid Hormones on Rat Air Pouch Model of Inflammation.

BACKGROUND: Many studies showed anti-inflammatory potential of thyroid hormones, but no direct report available showing influence of thyroid hormones on inflammation state. Therefore, in present study anti-inflammatory and antioxidative role of thyroid hormones being evaluated on rat air pouch model of inflammation. METHODS: Reference doses of both the thyroid hormones triiodothyronine (T3) and thyroxine (T4) were administered to rat airpouches. Air pouch model was developed by injecting air into intra-scapular region of animals, followed by carrageenan administration (AP+C). Control animals injected only with air (AP). RESULTS: In AP+C, group an increase was observed in exudate levels of TNF-α, total leukocytes, polymophonuclear cells and mononuclear cells. An increase was also observed in exudates and tissue lipid peroxidation, nitrite and reduced glutathione. These changes were reverted back by the administration of indomethacin (I) or T3or T4. However, effect was more pronounced in case of T3, as compared to other groups on most of the studied parameters. Histopathological changes were also observed in AP+C group, as compared to AP alone and these alterations were also normalized by the administration of I or T3 or T4. In silico interaction of both the thyroid hormones with cyclooxygenase (COX-2) was studied and compared with standard drugs indomethacin and celecoxib. CONCLUSION: We conclude thyroid hormones have anti-inflammatory potential i.e. mainly mediated through their structural similarity with anti-inflammatory drugs.

Study on gluco-regulatory potential of glimepiride sulfonamide using in silico, in vitro and in vivo approaches.

Glimepiride sulfonamide (GS) is a drug intermediate to synthesize glimepiride (antidiabetic drug). We hypothesized that GS exerts gluco-regulatory effect because GS is comprised of the structural components of dipeptidyl peptidase-IV (DPP-IV) inhibitors sitagliptin and DPP-728and glimepiride (sulfonylurea based antidiabetic drug).We analyzed the drug-likeness and docking efficiency of GS with DPP-IV using in silico tools. Also DPP-IV inhibition assays were conducted in vitro. Gluco-regulatory potential and parameters of drug safety were evaluated on normal euglycemic and streptozotocin (STZ) induced diabetic rats. We observed strong drug-likeness and DPP-IV binding efficiency of GS. Similarly, profound DPP-IV inhibition was also observed in vitro. Studies on euglycemic and STZ induced diabetic rats revealed antidiabetic potential for GS without significant change in the studied toxicological parameters. Glimepiride sulfonamide has antidiabetic potential mainly through DPP-IV inhibition, but also through insulin stimulation and alpha-amylase inhibition.

Diabetogenic effects of Parthinium hysterophorous induced allergic rhinitis.

Diabetes mellitus (DM) is known to be associated with the cytokines secreted by Th1 cells, while allergic rhinitis (AR) is mainly regulated by Th2 cytokines. According to Th1/Th2 paradigm, there is an inverse relationship between Th1 and Th2 cytokines and resultantly, both the aforesaid diseases are also inversely correlated. On the other hand, numbers of clinical reports suggest every possible correlation between DM and AR including positive, negative and neutral. However, till to date, no experimental report available, suggesting the changes in glucose homeostasis of animal model(s) of allergic rhinitis, if any. Therefore, in the present study we have observed the changes in glucose homeostasis of the animals bearing AR induced by Parthinium hysterophorous (PH). The condition of AR was induced by intranasal instillations of the acetone extract of PH. At the end of experimentation, various parameters for AR and DM were evaluated. A significant increase was observed in total leukocytes in nasal fluid, serum glucose, thyroxine, dyslipidemia and activity of α-amylase, pancreatic lipid peroxidation, serum and pancreatic nitrite with a concomitant reduction in serum calcium, triiodothyronine, hepatic glycogen and activity of phosphoglucomutase. However, serum insulin, TSH, pancreatic calcium and hepatic glucokinase increased non-significantly. Immune cells infiltration and increased intra alveolar space were observed in lungs tissue, while alterations were also observed in pancreas of AR treated animals. The induction of AR led to the diabetogenic changes to rats via exerting multifaceted metabolic defects in the biochemical machinery regulating glucose homeostasis.

DPP-IV inhibitory potential of naringin: an in silico, in vitro and in vivo study.

The incretin based therapies are an emerging class of antidiabetic drugs, with two categories: one is glucagone like peptide-1 (GLP-1) agonists and the other one is dipeptidyl peptidase (CD26; DPP-IV) inhibitors. However, in the DPP-IV inhibitors category only few compounds are commercially available and also have some undesirable effects. Therefore, in the present work we tried to explore a naturally occurring compound naringin for its potential DPP-IV inhibition and antidiabetic potential. It is noteworthy that this compound is abundantly present in orange peel and thus may provide cost effective treatment for diabetes, especially type 2 diabetes mellitus. In the present study, we have conducted virtual docking study and observed tight binding of naringin, as shown by higher negative values of H bond lengths, while in vitro DPP-IV inhibition assay has also shown better inhibition by naringin. In vivo study, in response to 10 days administration of 40 mg/kg of naringin twice daily to Wistar albino rats, inhibited the serum levels of DPP-IV activity, random glucose concentration with concomitant increase in insulin levels. All the comparisons were made with the standard commercially available drug sitagliptin.

Evaluation of antioxidative and anti-inflammatory potential of hesperidin and naringin on the rat air pouch model of inflammation.

BACKGROUND: Anti-inflammatory and antioxidative potential of hesperidin and naringin was carried out considering the rat air pouch model of inflammation. METHODS: Reference dose of hesperidin (H) or naringin (N) or indomethacin (I) was administered to the rat air pouches. The pouches were induced by injecting sterile air into the intra-scapular region of the rats followed by carrageenan (AP + C) administration. Rats injected only with air (AP) served as controls. RESULTS: The AP + C group, showed an increase in the exudate lipid peroxidation (LPO), reduced glutathione (GSH), TNF-α, activity of catalase (CAT), total leukocytes and neutrophils along with tissue edema and infiltration of inflammatory cells. Increases in tissue nitrite, LPO, GSH, SOD (superoxide dismutase) and CAT were recorded. Increased CAT and SGPT with concomitant decrease in ALP were observed in serum. When treated with indomethacin (AP + C + I), all the alterations in the exudate, tissue and serum shifted towards normalcy, except LPO in exudate and nitrite in tissue, while, hesperidin (AP + C + H) or naringin (AP + C + N) treatment normalized all the alterations. CONCLUSION: It seems that both naringin and hesperidin are anti-inflammatory and antioxidative in nature, but hesperidin proved to be better than indomethacin and naringin because of more pronounced pharmacological actions without tissue toxicity.

Protective role of Mangifera indica, Cucumis melo and Citrullus vulgaris peel extracts in chemically induced hypothyroidism.

An investigation was made to evaluate the pharmacological importance of fruit peel extracts of Mangifera indica (MI), Citrullus vulgaris (CV) and Cucumis melo (CM) with respect to the possible regulation of tissue lipid peroxidation (LPO), thyroid dysfunctions, lipid and glucose metabolism. Pre-standardized doses (200mg/kg of MI and 100mg/kg both of CV and CM), based on the maximum inhibition in hepatic LPO, were administered to Wistar albino male rats for 10 consecutive days and the changes in tissue (heart, liver and kidney) LPO and in the concentrations of serum triiodothyronine (T(3)), thyroxin (T(4)), insulin, glucose, alpha-amylase and different lipids were examined. Administration of three test peel extracts significantly increased both the thyroid hormones (T(3) and T(4)) with a concomitant decrease in tissue LPO, suggesting their thyroid stimulatory and antiperoxidative role. This thyroid stimulatory nature was also exhibited in propylthiouracil (PTU) induced hypothyroid animals. However, only minor influence was observed in serum lipid profile in which CM reduced the concentrations of total cholesterol and low-density lipoprotein-cholesterol (LDL-C), while CV decreased triglycerides and very low-density lipoprotein-cholesterol (VLDL-C). When the combined effects of either two (MI+CV) or three (MI+CV+CM) peel extracts were evaluated in euthyroid animals, serum T(3) concentration was increased in response to MI+CV and MI+CV+CM treatments, while T(4) level was elevated by the combinations of first two peels only. Interestingly, both the categories of combinations increased T(4) levels, but not T(3) in PTU treated hypothyroid animals. Moreover, a parallel increase in hepatic and renal LPO was observed in these animals, suggesting their unsafe nature in combination. In conclusion the three test peel extracts appear to be stimulatory to thyroid functions and inhibitory to tissue LPO but only when treated individually.