Papers by Sushruta Koppula
Tropical Journal of Pharmaceutical Research, 2013
Purpose: To investigate the antioxidant and anti-neuroinflammatory potentials of Olea europaea Li... more Purpose: To investigate the antioxidant and anti-neuroinflammatory potentials of Olea europaea Linn. fruit pulp (OFP-EA) extract in LPS-stimulated BV-2 microglial cells. Methods: Cell viabilities were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Antioxidant properties were evaluated using 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activity. Lipopolysaccharide (LPS) was used to stimulate BV-2 microglia. Nitric oxide (NO) production was measured using Griess assay. Inducible NO synthase (iNOS) expression and tumor necrosis factor-alpha (TNF-α) production were measured using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Results: OFP-EA extract significantly (p<0.001 at 20-200 µg/ml, respectively) scavenged the free radicals in a dose-dependent fashion. The increased levels of No stimulated by LPS (34±2.41) were also inhibited by OFP-EA extract significantly and concentration dependently (27±2.32, 21±2.54, 17±1.92 and 11±1.94 at 10, 20, 40 and 80 µg/ml, respectively). Further, OFP-EA suppressed the elevated levels iNOS expression and TNF-α production (p<0.001 at 20, 40 and 80 µg/ml) in LPSstimulated BV-2 cells. Conclusion: Results indicate that OFP-EA extract exhibited strong antioxidant properties and inhibited the excessive production of pro-inflammatory mediators such as NO, iNOS and TNF-α in LPSstimulated BV-2 cells. The antioxidant activity exhibited by OFP-EA extract might play a critical role in ameliorating the inflammatory processes in LPS-stimulated BV-2 microglial cells.
Journal of Ginseng Research, 2016
Background: Elevated testicular temperature disrupts spermatogenesis and causes infertility. In t... more Background: Elevated testicular temperature disrupts spermatogenesis and causes infertility. In the present study, the protective effect of enzymatically biotransformed Panax ginseng Meyer by pectinase (GINST) against chronic intermittent heat stress-induced testicular damage in rats was investigated. Methods: Male SpragueeDawley rats (4 wk old, 60e70 g) were divided into four groups: normal control (NC), heat-stress control (HC), heat-stress plus GINST-100 mg/kg (HG100), and heat-stress plus GINST-200 mg/kg (HG200) treatment groups. Each dose of GINST (100 mg/kg and 200 mg/kg) was mixed separately with a regular pellet diet and was administered orally for 24 wk. For inducing heat stress, rats in the NC group were maintained at 25 C, whereas rats in the HC, HG100, and HG200 groups were exposed to 32 AE 1 C for 2 h daily for 6 mo. At week 25, the testes and serum from each animal were analyzed for various parameters. Results: Significant (p < 0.01) changes in the sperm kinematic values and blood chemistry panels were observed in the HC group. Furthermore, spermatogenesis-related molecules, sex hormone receptors, and selected antioxidant enzyme expression levels were also altered in the HC group compared to those in the NC group. GINST (HS100 and HS200) administration significantly (p < 0.05) restored these changes when compared with the HC group. For most of the parameters tested, the HG200 group exhibited potent effects compared with those exhibited by the HG100 group. Conclusion: GINST may be categorized as an important medicinal herb and a potential therapeutic for the treatment of male subfertility or infertility caused by hyperthermia.
Journal of Radiation Research, 2013
Radiation-induced oral mucositis is a dose-limiting toxic side effect for patients with head and ... more Radiation-induced oral mucositis is a dose-limiting toxic side effect for patients with head and neck cancer. Numerous attempts at improving radiation-induced oral mucositis have not produced a qualified treatment. Ginseng polysaccharide has multiple immunoprotective effects. Our aim was to investigate the effectiveness of Korean red ginseng (KRG) on radiation-induced damage in the human keratinocyte cell line HaCaT and in an in vivo zebrafish model. Radiation inhibited HaCaT cell proliferation and migration in a cell viability assay and wound healing assay, respectively. KRG protected against these effects. KRG attenuated the radiationinduced embryotoxicity in the zebrafish model. Irradiation of HaCaT cells caused apoptosis and changes in mitochondrial membrane potential (MMP). KRG inhibited the radiation-induced apoptosis and intracellular generation of reactive oxygen species (ROS), and stabilized the radiation-induced loss of MMP. Western blots revealed KRG-mediated reduced expression of ataxia telangiectasia mutated protein (ATM), p53, c-Jun N-terminal kinase (JNK), p38 and cleaved caspase-3, compared with their significant increase after radiation treatment. The collective results suggest that KRG protects HaCaT cells by blocking ROS generation, inhibiting changes in MMP, and inhibiting the caspase, ATM, p38 and JNK pathways. Keywords: Korean red ginseng (KRG); head and neck cancer; radiation-induced mucositis; apoptosis; radioprotection been made in managing radiation-induced toxicity, oral mucositis remains a relatively major side effect [2-5]. Oral mucositis is accompanied by altered taste, pain, dry mouth and decreased appetite, and, in severe cases, ulceration, which can decrease nutritional uptake. The consequence can often be a significant impact on the quality of life; and interruption of oral therapy can worsen the prognosis [4]. About 50-90% of cancer patients who undergo radiation therapy † These authors contributed equally to this work.
Pharmaceutical Biology, 2022
Abstract Context Cordycepin (COR), from Cordyceps militaris L., (Cordycipitaceae), is a valuable ... more Abstract Context Cordycepin (COR), from Cordyceps militaris L., (Cordycipitaceae), is a valuable agent with immense health benefits. Objective The protective effects of COR in ageing-associated oxidative and apoptosis events in vivo and hydrogen peroxide (H2O2)-exposed spermatogenesis gene alterations in TM3 Leydig cells was investigated. Materials and methods Male Sprague-Dawley rats were divided into young control (YC), aged control (AC) and COR treated (COR-20) aged groups. COR-20 group received daily doses of COR (20 mg/kg) for 6 months. Cell viability and hormone levels were analysed by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and enzyme immunoassay kits with COR treated at 1, 5, and 10 μg/mL. Oxidative enzymes, spermatogenic, and apoptotic expression in testis tissues were evaluated by Western blotting and real-time RT-PCR. Results COR treatment (1, 5, and 10 μg/mL) significantly (p < 0.05 ∼ p < 0.001) inhibited the H2O2-induced decrease in the percentage of viable cells (from 63.27% to 71.25%, 85.67% and 93.97%, respectively), and reduced the malondialdehyde (MDA) content (from 4.28 to 3.98, 3.14 and 1.78 nM MDA/mg protein, respectively). Further, the decreased antioxidant enzymes (glutathione-S-transferase mu5, glutathione peroxidase 4 and peroxiredoxin 3), spermatogenesis-related factors (nectin-2 and inhibin-α) and testosterone levels in H2O2-exposed TM3 cells were significantly (p < 0.05 ∼ p < 0.001) ameliorated by COR. In aged rats, COR (20 mg/kg) restored the altered enzymatic and non-enzymatic antioxidative status and attenuated the apoptotic p53 and Bax/Bcl-2 expression significantly (p < 0.05). Conclusion COR might be developed as a potential agent against ageing-associated and oxidative stress-induced male infertility.
Reproduction (Cambridge, England), Jun 1, 2017
Testicular hyperthermia is well studied to cause impaired spermatogenesis. In the present study, ... more Testicular hyperthermia is well studied to cause impaired spermatogenesis. In the present study, the protective effect of enzymatically modified (pectinase-treated) Panax ginseng (GINST) against intermittent sub-chronic heat stress-induced testicular damage in rats was investigated. Male Sprague-Dawley rats were divided into four groups: normal control (NC), heat-stressed control (HC), heat-stressed plus GINST-100 mg/kg/day (HG100) and heat-stressed plus GINST-200 mg/kg/day (HG200) treatment groups. GINST (100 and 200 mg/kg/day) was mixed separately with a regular pellet diet and was administered orally for 8 weeks starting from 1 week before heat exposure. Parameters such as organ weight, blood chemistry, sperm kinetic values, expression of antioxidant enzymes, spermatogenesis molecules and sex hormone receptors levels were measured. Data revealed that kidney and epididymis weight were significantly (P < 0.05) decreased with heat stress and recovered by GINST treatment. Further,...
International Journal of Molecular Sciences, 2021
Theasinensin A (TSA) is a major group of catechin dimers mainly found in oolong tea and black tea... more Theasinensin A (TSA) is a major group of catechin dimers mainly found in oolong tea and black tea. This compound is also manufactured with epigallocatechin gallate (EGCG) as a substrate and is refined after the enzyme reaction. In previous studies, TSA has been reported to be effective against inflammation. However, the effect of these substances on skin melanin formation remains unknown. In this study, we unraveled the role of TSA in melanogenesis using mouse melanoma B16F10 cells and normal human epidermal melanocytes (NHEMs) through reverse transcription polymerase chain reaction (RT-PCR), Western blotting analysis, luciferase reporter assay, and enzyme-linked immunosorbent assay analysis. TSA inhibited melanin formation and secretion in α-melanocyte stimulating hormone (α-MSH)-induced B16F10 cells and NHEMs. TSA down-regulated the mRNA expression of tyrosinase (Tyr), tyrosinase-related protein 1 (Tyrp1), and Tyrp2, which are all related to melanin formation in these cells. TSA w...
Asian Pacific Journal of Tropical Biomedicine, 2021
of Low concentrations of doxycycline attenuates FasL-induced apoptosis in HeLa cells
Indian Journal of Pharmaceutical Sciences, 2020
This is an open access article distributed under the terms of the Creative Commons Attribution-No... more This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms
Journal of Ethnopharmacology, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Journal of Functional Foods, 2016
Abstract The protective effects of Korean red ginseng (KRG; Panax ginseng Meyer) aqueous extract ... more Abstract The protective effects of Korean red ginseng (KRG; Panax ginseng Meyer) aqueous extract against doxorubicin (DOX)-induced testicular damage in rats was investigated. DOX (1 mg⋅mL −1 ⋅kg −1 ⋅week −1 ) was administrated intraperitoneally for 8 weeks and KRG extract was administrated orally for 9 weeks (100 or 200 mg/kg/day). The serum sex hormone levels, sperm kinematic parameters, histopathological parameters and protein expression levels were determined. DOX distinctly damaged the histology of the rat testes and decreased the sex hormonal levels, spermatogenesis, seminiferous tubular diameter, and testes weight. Further, the protein expression levels of peroxiredoxin, glutathione- S -transferase, nectin-2, inhibin-α, and cAMP response element binding protein were suppressed in DOX-treated rats. In contrast, KRG extract ameliorated the changes induced by DOX. Data indicated that KRG ameliorated DOX-induced testicular damage in rats by modulating the antioxidant system and hormonal imbalance. In conclusion, KRG can be used as a functional food and/or adjuvant for the prevention of reproductive damage caused by DOX.
Molecules
Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by the dysregulation of cyto... more Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by the dysregulation of cytokines and other immune mediators. JAK/STAT is a classical signal transduction pathway involved in various biological processes, and its dysregulation contributes to the key aspects of AD pathogenesis. Suppressor of cytokine signaling (SOCS) proteins negatively regulate the immune-related inflammatory responses mediated by the JAK/STAT pathway. JAK/STAT-mediated production of cytokines including IL-4, IL-13, IL-31, and TSLP inhibits the expression of important skin barrier proteins and triggers pruritus in AD. The expression of SOCS proteins regulates the JAK-mediated cytokines and facilitates maintaining the skin barrier disruptions seen in AD. STATs are crucial in dendritic-cell-activated Th2 cell differentiation in the skin, releasing inflammatory cytokines, indicating that AD is a Th2-mediated skin disorder. SOCS proteins aid in balancing Th1/Th2 cells and, moreover, regulate the onse...
Journal of Inflammation Research, 2021
The pathogenesis of osteoarthritis (OA) is characterized by joint degeneration. The pro-inflammat... more The pathogenesis of osteoarthritis (OA) is characterized by joint degeneration. The pro-inflammatory cytokine interleukin (IL)-1β plays a vital role in the pathogenesis of OA by stimulation of specific signaling pathways like NF-κB, PI3K/Akt, and MAPKs pathways. The catabolic role of growth factors in the OA may be inhibited cytokineactivated pathogen. The purpose of this study was to investigate the potential effects of insulin-like growth factor-1 (IGF-1) on IL-1β-induced apoptosis in rabbit chondrocytes in vitro and in an in vivo rabbit knee OA model. Methods: In the present study, the OA developed in chondrocyte with the treatment of IL-1β and articular cartilage ruptures by removal of cartilage from the rabbit knee femoral condyle. After IGF-1 treatment, immunohistochemistry and qRT-PCR were identified OA expression with changes in MMPs (matrix metalloproteinases). The production of ROS (intracellular reactive oxygen species) in the OA was detected by flow cytometry. Further, the disease progression was microscopically investigated and pathophysiological changes were analyzed using histology. The NF-κB, PI3K/Akt and P38 (MAPK) specific pathways that are associated with disease progression were also checked using the Western blot technique. Results: The expression of MMPs and various apoptotic markers are down-regulated following administration of IGF-1 in a dose-dependent fashion while significantly upregulation of TIMP-1. The results showed that higher levels of ROS were observed upon treatment of chondrocytes and chondral OA with IL-1β. Collectively, our results indicated that IGF-1 protected NF-κB pathway by suppression of PI3K/Akt and MAPKs specific pathways. Furthermore, the macroscopic and pathological investigation showed that it has a chondroprotective effect by the formation of hyaline cartilage. Conclusion: Our results indicate a protective effect of IGF-1 against OA pathogenesis by inhibition of NF-κB signaling via regulation of the MAPK and PI3K/Akt signaling pathways and prevention of apoptosis by suppression of ROS production.
Molecules, 2021
Lindera obtusiloba Blume (family, Lauraceae), native to Northeast Asia, has been used traditional... more Lindera obtusiloba Blume (family, Lauraceae), native to Northeast Asia, has been used traditionally in the treatment of trauma and neuralgia. In this study, we investigated the neuroinflammatory effect of methanol extract of L. obtusiloba stem (LOS-ME) in a scopolamine-induced amnesia model and lipopolysaccharide (LPS)-stimulated BV2 microglia cells. LOS-ME downregulated the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, inflammatory cytokines, and inhibited the phosphorylation of nuclear factor kappa-B (NF-ĸB) and extracellular signal-regulated kinase (ERK) in LPS-stimulated BV2 cells. Male C57/BL6 mice were orally administered 20 and 200 mg/kg of LOS-ME for one week, and 2 mg/kg of scopolamine was administered intraperitoneally on the 8th day. In vivo behavioral experiments (Y-maze and Morris water maze test) confirmed that LOS-ME alleviated cognitive impairments induced by scopolamine and the amount of iNOS expression decreased in the hippocampus of...
Molecules, 2022
Testicular oxidative stress is one of the most common factors underlying male infertility. Welted... more Testicular oxidative stress is one of the most common factors underlying male infertility. Welted thistle, Carduus crispus Linn., and its bioactive principles are attracting scientific interest in treating male reproductive dysfunctions. Here, the protective effects of apigenin isolated from C. crispus against oxidative damage induced by hydrogen peroxide (H2O2) and dysregulation in spermatogenesis associated parameters in testicular sperm cells was investigated. Cell viabilities, ROS scavenging effects, and spermatogenic associated molecular expressions were measured by MTT, DCF-DA, Western blotting and real-time RT-PCR, respectively. A single peak with 100% purity of apigenin was obtained in HPLC conditions. Apigenin treated alone (2.5, 5, 10 and 20 µM) did not exhibit cytotoxicity, but inhibited the H2O2-induced cellular damage and elevated ROS levels significantly (p < 0.05 at 5, 10 and 20 µM) and dose-dependently. Further, H2O2-induced down-regulation of antioxidant (glutath...
Background Doxycycline (DC) has been shown to possess non-antibiotic properties including Fas/Fas... more Background Doxycycline (DC) has been shown to possess non-antibiotic properties including Fas/Fas Ligand (FasL)-mediated apoptosis against several tumor types in the concentration range of 10–40 µg/mL. However, the effect of DC in apoptotic signaling at much low concentrations was not studied. Methods The present study investigated the attenuation effect of low dose of DC on FasL-induced apoptosis in HeLa cell by the methods of MTT assay, fluorescence microscopy, DNA fragmentation, flow cytometry analysis, and western blotting. Results and conclusion In the present findings we showed that low concentration of DC (<2.0 µg/mL) exhibited protective effects against FasL-induced apoptosis in HeLa cells. FasL treatment to HeLa cells resulted in a concentration-dependent induction of cell death, and treatment with low concentrations of DC (0.1–2 µg/mL) significantly (p
EXCLI Journal, 2021
Coriandrum sativum Linn. (family: Umbelliferae; C. sativum), is a potential herb widely used as a... more Coriandrum sativum Linn. (family: Umbelliferae; C. sativum), is a potential herb widely used as a spice and traditional medicine. In the present work, the effects of C. sativum fruit extract (CSE), against lipopolysaccharide (LPS)-stimulated BV-2 microglia-mediated neuroinflammation in vitro and 1-methyl-4 phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) animal model in vivo was investigated. LPS-stimulated increase in nitric oxide (NO), inducible NO synthase, cyclooxygenase-2, interleukin-6 and tumor necrosis factor-alpha were significantly (p < 0.05 ~ p < 0.001) inhibited by CSE (25, 50 and 100 μg/mL) in BV-2 microglial cells. Further, CSE inhibited the LPS-induced nuclear factor of kappa-beta activation and IκB-α phosphorylation in BV-2 microglia. In vivo studies, CSE (100, 200 and 300 mg/kg) ameliorated the MPTP (25 mg/kg, i.p.)-induced changes in locomotor, cognitive and behavior functions evaluated by rotarod, passive avoidance and open fi...
Indian Journal of Pharmaceutical Sciences, 2014
Houttuynia cordata Thunb (Saururaceae) is a traditional medicinal herb used to treat several dise... more Houttuynia cordata Thunb (Saururaceae) is a traditional medicinal herb used to treat several disease symptoms. The present study was focused on the hepatoprotective effects of H. cordata ethyl acetate extract in experimental mice. Further the antioxidant potential of the extract was also evaluated to substantiate its hepatoprotective properties. Carbon tetrachloride-induced hepatic damage in mice was used to measure the serum biochemical parameters. Morphological changes in hepatocyte architecture were studied by haematoxylin and eosin staining. In vitro alkyl and hydroxyl free radical scavenging assays were performed to evaluate the antioxidant effect. Administration of H. cordata extract significantly reduced the elevated serum levels and regulated the altered levels of serum cholesterol in carbon tetrachloride-treated mice (P<0.05). The morphological changes in hepatocyte architecture were also reversed by H. cordata treatment. Further, the extract showed significant antioxida...
EXCLI Journal, 2020
The quest for chemical entities able to curb the action of the phosphoinositide 3-kinase, (PI3K)/... more The quest for chemical entities able to curb the action of the phosphoinositide 3-kinase, (PI3K)/protein kinase B (AKT) signaling pathways is evolving as a potential therapeutic strategy for the treatment and/or prevention of neurodegenerative disorders including Alzheimer's disease (AD). In this study, the effects of a PI3K inhibitor, AS605240 on cognitive dysfunction and antioxidative defense parameters against intra-cerebroventricular-streptozotocin (ICV-STZ)-induced rat model of sporadic AD was evaluated. ICV administration of a single dose of STZ (3 mg/kg) was performed to induce behavioral and biochemical changes in rats using the stereotaxic technique. Animals were administered with varying doses of AS605240 (5, 10 and 15 mg/kg) orally, 1 h before ICV-STZ on day 1 and continued once daily for four weeks. The behavioral parameters (passive avoidance and Morris water maze), antioxidative defense parameters, amyloid-beta (Aβ) protein expression by Western blotting and immuno...
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Papers by Sushruta Koppula