Vanillic acid mitigates hyperinsulinemia induced ER stress mediated altered calcium homeostasis, MAMs distortion and surplus lipogenesis in HepG2 cells.

Hyperinsulinemia (HI) induced insulin resistance (IR) and associated pathologies are the burning and unsolvable issues in diabetes treatment. The cellular, molecular and biochemical events associated with HI are not yet elucidated. Similarly, no focused research on designing therapeutic strategies with natural products for attenuation of HI are seen in literature. Keeping this in mind we planned the present study to evaluate the alterations occurring at ER/Ca2+ homeostasis/mitochondria associated endoplasmic reticulum membranes (MAMs) in HepG2 cells during HI and to evaluate the possible beneficial effect of vanillic acid (VA) to mitigate the complications. An in vitro model of HI was established by treating HepG2 cells with human insulin (1 µM) for 24 h. Then, ER stress, Ca2+ homeostasis, MAMs, IR and hepatic lipogenesis were studied at protein level. Various proteins critical to ER, Ca2+ homeostasis and MAMs such as p-IRE-1α, ATF6, p-PERK, p-eIF2α, CHOP, XBP1, p-CAMKII, InsP3R, SERCA, JNK, GRP78, VDAC, Cyp D, GRP75, MFN2, PTEN and mTORC were studied and found altered significantly causing ER stress, defect in Ca2+ movements and distortion of MAMs. The decreased expression of IRS2 and an unaltered expression of IRS1 confirmed the development of selective insulin resistance in hepatocytes during HI and this was the crucial factor for the progression of the hepatic lipid accumulation. We found simultaneous treatment of VA is beneficial up to a certain extent to protect HepG2 cells from the adverse effect of HI via its antioxidant, antilipogenic, mitochondrial and ER protection properties.

In vitro and in vivo anti-inflammatory and anti-arthritic effect of Tinospora cordifolia via modulation of JAK/STAT pathway.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disorder causing cartilage and joint degeneration. In spite of the availability of several robust drugs like biologics, most of the patients are unresponsive, and reports of severe adverse effects following long-term use are also there. Subsequently the use of natural plant-based products in RA therapy is broadening over the years. Tinospora cordifolia is a widely used medicinal plant in Ayurveda against various inflammatory disorders including RA. However, there is very limited knowledge regarding the actual molecular events responsible for its therapeutic effect, and this has limited its acceptance among the professionals. PURPOSE: To explore the anti-inflammatory and anti-arthritic effect of hydro-alcoholic extract from Tinospora cordifolia. METHODS: The rich polyphenol nature of the extract was elucidated using HPLC. LPS-stimulated murine macrophage cell line RAW 264.7 was used for in vitro studies, and collagen-induced arthritis (CIA) model was used for in vivo studies. RESULTS: The polyphenols in TCE were identified using HPLC. TCE effectively downregulated the level of pro-inflammatory mediators (IL-6, TNF-α, PGE2, and NO) in LPS-stimulated RAW 264.7 cells. Subsequently the upregulated expression of COX-2 and iNOS following LPS stimulation were also downregulated by TCE. Furthermore, TCE targeted the upstream kinases of the JAK/STAT pathway, a crucial inflammatory pathway. The expression of VEGF, a key angiogenic factor as well as an inflammatory mediator was also decreased following pre-treatment with TCE. The anti-arthritic effect of TCE (150 mg/kg) was evaluated in the CIA model as well. From the results of histopathology, oral administration of TCE was found to be effective in reducing the clinical symptoms of arthritis including paw edema, erythema, and hyperplasia. In vivo results validated the in vitro results and there was a significant reduction in serum level of pro-inflammatory cytokines and mediators (IL-6, TNF-α, IL-17, NO, and PGE2). The phosphorylation of STAT3 and the expression of VEGF were also downregulated following TCE treatment. CONCLUSION: Our study provided a detailed insight into the molecular events associated with anti-inflammatory and anti-arthritic effect of Tinospora cordifolia.

Tangeretin alleviates Tunicamycin-induced endoplasmic reticulum stress and associated complications in skeletal muscle cells.

Endoplasmic reticulum (ER) stress and associated oxidative stress are involved in the genesis and progression of skeletal muscle diseases such as myositis and atrophy or muscle wasting. Targeting the ER stress and associated downstream pathways can aid in the development of better treatment strategies for these diseases with limited therapeutic approaches. There is a growing interest in identifying natural products against ER stress due to the lower toxicity and cost effectiveness. In the present study, we investigated the protective effect of Tangeretin, a citrus methoxyflavone found in citrus peels against Tunicamycin (pharmacological ER stress inducer)-induced ER stress and associated complications in rat skeletal muscle L6 cell lines. Treatment with Tunicamycin for a period of 24 h resulted in the upregulation of ER stress marker proteins, ER resident oxidoreductases and cellular reactive oxygen species (ROS). Co-treatment with Tangeretin was effective in alleviating Tunicamycin-induced ER stress and associated redox-related complications by significantly downregulating the unfolded protein response (UPR), ER resident oxidoreductase proteins, cellular ROS and improving the antioxidant enzyme activity. Tunicamycin also induced upregulation of phosphorylated p38 MAP Kinase and loss of mitochondrial membrane potential. Tangeretin significantly reduced the levels of phosphorylated p38 MAP Kinase and improved the mitochondrial membrane potential. From the results, it is evident that Tangeretin can be explored further as a potential candidate for skeletal muscle diseases involving protein misfolding and ER stress.

Ferulic acid attenuates high glucose-induced MAM alterations via PACS2/IP3R2/FUNDC1/VDAC1 pathway activating proapoptotic proteins and ameliorates cardiomyopathy in diabetic rats.

BACKGROUND: Diabetic cardiomyopathy (DCM) is one of the severe complications of diabetes with no known biomarkers for early detection. Mitochondria-associated endoplasmic reticulum membranes (MAM) are less studied subcellular targets but an emerging area for exploration in metabolic disorders including DCM. We herein studied the role of MAMs and downstream mitochondrial functions in DCM. We also explored the efficacy of ferulic acid (FeA) against DCM via modulation of MAM and its associated signaling pathway. METHODS: The H9c2 cardiomyoblast cells were incubated with high concentration (33 mM) of d-glucose for 48 h to create a high glucose ambience in vitro. The expression of various critical proteins of MAM, mitochondrial function, oxidative phosphorylation (OxPhos) and the genesis of apoptosis were examined. The rats fed with high fat/high fructose/streptozotocin (single dose, i.p.) were used as a diabetic model and analyzed the insulin resistance and markers of cardiac hypertrophy and apoptosis. RESULTS: High glucose conditions caused the upregulation of MAM formation via PACS2, IP3R2, FUNDC1, and VDAC1 and decreased mitochondrial biogenesis, fusion and OxPhos. The upregulation of mitochondria-driven SMAC-HTRA2-ARTS-XIAP apoptosis and other cell death pathways indicate their critical roles in the genesis of DCM at the molecular level. The diabetic rats also showed cardiomyopathy with increased heart mass index, TNNI3K, troponin, etc. FeA effectively prevented the high glucose-induced MAM alterations and associated cellular anomalies both in vitro and in vivo. CONCLUSION: High glucose-induced MAM distortion and subsequent mitochondrial dysfunctions act as the stem of cardiomyopathy. MAM could be explored as a potential target to treat diabetic cardiomyopathy. Also, the FeA could be an attractive nutraceutical agent for diabetic cardiomyopathy.

Cinnamic acid is beneficial to diabetic cardiomyopathy via its cardioprotective, anti-inflammatory, anti-dyslipidemia, and antidiabetic properties.

Diabetes-related health issues are increasing day by day in public, and diabetic cardiomyopathy (DCM) is one serious issue among them. There is a lack of proper strategy to control and manage DCM. Here we are attempting a nutraceutical-based approach to protect the heart from DCM. The beneficial effect of cinnamic acid (CiA), was evaluated in an experimental model of diabetes. For this, diabetic model was created by feeding male Wistar rats with a high fat, high fructose diet for 6 months and a single dose of streptozotocin (25 mg/kg bwt). Metformin was used as the positive control. The diabetic rats showed insulin resistance, myocardial injury, and a significant increase of total cholesterol, triglycerides, and LDL. Development of DCM was evident from the increased cardiac mass index, LDH, CKMB, ANP, and CRP levels in the diabetic group. There was a significant increase in the levels of cardiac hypertrophy markers like TGF-ß and ß-MHC in the hearts of diabetic rats revealing DCM. Pro-inflammatory cytokines (TNF-α, IL-6) and lipid peroxides were significantly elevated in the serum of diabetic rats. Histopathology revealed inflammation and necrosis in the heart of diabetic rats confirming DCM. Oral administration of CiA (5 and 10 mg/kg bwt) prevented the development of DCM via its cardioprotective, anti-inflammatory, anti-dyslipidemia potential, and antidiabetic properties. Similarly, metformin (50 mg/kg bwt) has also shown protection against DCM. We conclude from this study that CiA is found to be beneficial against DCM and recommend more detailed preclinical and clinical studies to develop CiA-based nutraceutical against DCM.

A novel aureothin diepoxide derivative from Streptomyces sp. NIIST-D31 strain.

A novel vicinal diepoxide of alloaureothin was isolated from Streptomyces sp. NIIST-D31 strain along with three carboxamides, p-aminobenzoic acid and 1,6-dimethoxyphenazine. Exhaustive 2D NMR analysis and analysis of experimental, theoretical CD spectra aided in establishing the structure of compound 1. Compound 1 inhibits adipogenesis and accumulation of lipid droplets during the differentiation of 3T3-L1 cells.

Methylglyoxal induces ambience for cancer promotion in HepG2 cells via Warburg effect and promotes glycation.

Methylglyoxal (MGO) is a toxic, highly reactive metabolite derived mainly from glucose and amino acids degradation. MGO is also one of the prime precursors for advanced glycation end products formation. The present research was performed to check whether MGO has any role in the promotion of cancer in HepG2 cells. For this, cells were incubated with MGO (50 µM) for 24 h and subjected to various analyses. Aminoguanidine (200 µM) was positive control. The various biochemical and protein expression studies, relevant to the MGO detoxification system, oxidative stress, and glycolysis were performed. MGO caused the reduction of expression of GLO 1 (27%) and GLO 2 (11%) causing weakening of the innate detoxification system. This is followed by an increase of RAGE (95%), AGEs or methylglyoxal adducts. We also observed hypoxia via estimation of oxygen consumption rate and surplus reactive oxygen species (ROS) (24%). To investigate the off-target effect of MGO we checked its effect on glucose transport, and its associated proteins. Glucose uptake was found to increase (15%) significantly with overexpression of GLUT 1 (35%). We also found a significant increase of glycolytic enzymes such as hexokinase II, phosphofructokinase 1, and lactate dehydrogenase along with lactate production. Observation of surplus ROS and enhanced glycolysis led us to check the expression of HIF 1α which is their downstream signaling pathway. Interestingly HIF 1α was found to increase significantly (35%). It is known that enhanced glycolysis and oxidative stress are catalysts for the overexpression of HIF 1α which in turn creates an ambience for the promotion of cancer. Aminoguanidine was able to prevent the adverse effect of MGO partially. This is the first study to show the potential of MGO for the promotion of cancer in the non-tumorigenic HepG2 cells via the Warburg effect and glycation.

In vitro and in vivo studies reveal the beneficial effects of chlorogenic acid against ER stress mediated ER-phagy and associated apoptosis in the heart of diabetic rat.

Endoplasmic reticulum (ER) and associated signaling pathways are involved in diabetic cardiomyopathy (DCM) however, detailed studies are not available. The present study investigated the role of ER stress and related pathways such as ER-phagy, apoptosis and their underlying mechanisms using appropriate models. Beneficial effect of chlorogenic acid was also evaluated against ER stress mediated DCM. H9c2 cells with high glucose (33 mM, in vitro model of hyperglycemia) showed significant activation of ER stress response (GRP78, PERK, IRE1α, ATF6α) and altered its regulatory proteins (PDI, ERO1α). Also, it enhanced ER-phagy through upregulation of Sec62, RTN3 and downregulation of FAM134B. High glucose caused apoptosis via increased levels of CHOP, caspase 12 and calnexin. All these proteins (PERK, IRE1α, ATF6α, RTN3, Sec62 and FAM134B) have been found to have a significant role in the functioning of heart such as excitation contraction coupling and we expect these alterations to induce cardiomyopathy during diabetes. This was confirmed in in vivo study too. High fat, high fructose diet with mild streptozotocin induced diabetic rats showed an increased expression of BNP confirming cardiac injury. We also noticed severe ER stress in the heart of diabetic animals. All these have contributed significantly into alterations in histopathology and increase of weight of the hearts. These findings clearly show that ER stress plays a vital protagonist in the progression of DCM. We also found chlorogenic acid is effective against hyperglycemia induced pathological alteration both in vitro as well as in vivo.

Downregulation of TLR4/MyD88/p38MAPK and JAK/STAT pathway in RAW 264.7 cells by Alpinia galanga reveals its beneficial effects in inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Alpinia galanga, commonly known as greater galangal or raasna, is widely used in Ayurveda against various inflammatory disorders. It is also known as Kulinjan, Aratha, Rasna or Sugandhamula. Some of the Ayurvedic preparations using the rhizome of Alpinia galanga are Rasnadi kashayam, Rasna panchakam, Rasnapthakam, and Rasnarendadi. The aromatic rhizome is the source of the drug greater galangal and it is also used as a spice in South and South East Asia. However, the molecular mechanism of action of A galanga against inflammation remains poorly understood. AIM OF THE STUDY: To elucidate the anti-inflammatory effect of hydroalcoholic extract of Alpinia galanga rhizome. STUDY DESIGN/METHOD: The mechanism of the anti-inflammatory effect of hydroalcoholic extract of Alpinia galanga (AGE) was investigated by enzyme-linked immunosorbent assay (ELISA), Western blot, and immunofluorescence in LPS stimulated murine macrophage cell line (RAW 264.7). HPLC analysis was done to elucidate the rich polyphenolic nature of AGE. RESULTS: The study showed that pre-treatment with AGE downregulated the release of pro-inflammatory mediators (IL-6, TNF-α, NO, and ROS) and stimulated the release of anti-inflammatory mediator IL-10 in LPS stimulated RAW 264.7 cells. The vital enzymes of inflammation (iNOS, COX-2, and MMP-9) were also downregulated by pre-treatment with AGE. AGE targeted the upstream elements of the inflammatory cascade by blocking LPS induced activation of TLR4 and JAK/STAT pathway. The phosphorylation of downstream kinases was significantly affected. The inhibition of nuclear translocation of NFκB further confirmed the specific inhibition of the TLR4 pathway. Particularly AGE inhibited the phosphorylation of JNK, p38, IκBα, and STAT. HPLC analysis of the AGE showed the polyphenol-rich nature of the extract. CONCLUSIONS: The results from this study provide firm evidence that AGE exerts its anti-inflammatory effect via modulation of TLR4 and JAK/STAT pathway.

Zerumin A attenuates the inflammatory responses in LPS-stimulated H9c2 cardiomyoblasts.

Zerumin A (ZA) is one of the potential components of Curcuma amada rhizomes, and it has been shown to possess a variety of pharmacological activities. This study deals with the beneficial activity of ZA in lipopolysaccharide (LPS)-stimulated inflammation in H9c2 cardiomyoblasts. Herein, H9c2 cells were preincubated with ZA for 1 h and stimulated with LPS for 24 h. The cells were analyzed for the expression of various pro-inflammatory mediators and signaling molecules. Results showed that the cell viability was significantly improved and reactive oxygen species production was alleviated remarkably with ZA pretreatment. We also found that ZA pretreatment significantly suppressed the upregulation of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) protein levels, and nitric oxide (NO) release in LPS-stimulated cells. In addition, ZA significantly ameliorated LPS-elicited overexpression of pro-inflammatory chemokines and cytokines such as monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor α (TNF- α), interferon-γ (IFN-γ), and interleukin-1 (IL-1) in H9c2 cells, and it upregulated the synthesis of the anti-inflammatory cytokine interleukin-10 (IL-10). Moreover, pretreatment with ZA and the mitogen-activated protein kinases (MAPK) pathway inhibitors also reduced the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinases (JNK), and p38. ZA significantly inhibited IkB-a phosphorylation and nuclear factor (NF)-kB p65 subunit translocation into nuclei. Overall data demonstrated that ZA protects cardiomyocytes against LPS injury by inhibiting NF-kB p65 activation via the MAPK signaling pathway in vitro. These findings suggest that ZA may be a promising agent for a detailed study for the prevention or treatment of myocardial dysfunction in sepsis.

Advanced glycation end products and their adverse effects: The role of autophagy.

The critical roles played by advanced glycation endproducts (AGEs) accumulation in diabetes and diabetic complications have gained intense recognition. AGEs interfere with the normal functioning of almost every organ with multiple actions like apoptosis, inflammation, protein dysfunction, mitochondrial dysfunction, and oxidative stress. However, the development of a potential treatment strategy is yet to be established. Autophagy is an evolutionarily conserved cellular process that maintains cellular homeostasis with the degradation and recycling systems. AGEs can activate autophagy signaling, which could be targeted as a therapeutic strategy against AGEs induced problems. In this review, we have provided an overview of the adverse effects of AGEs, and we put forth the notion that autophagy could be a promising targetable strategy against AGEs.

Impact of COVID-19 on the Cardiovascular System: A Review of Available Reports.

The recent emergence of the coronavirus disease 19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China is now a global health emergency. The transmission of SARS-CoV-2 is mainly via human-to-human contact. This virus is expected to be of zoonotic origin and has a high genome identity to that of bat derived SARS-like coronavirus. Various stringent measures have been implemented to lower person-to-person transmission of COVID-19. Particular observations and attempts have been made to reduce transmission in vulnerable populations, including older adults, children, and healthcare providers. This novel CoV enters the cells through the angiotensin-converting enzyme 2 (ACE2) receptor. There is a higher risk of COVID-19 infection among those with preexisting cardiovascular diseases (CVD), and it has been connected with various direct and indirect complications, including myocarditis, acute myocardial injury, venous thromboembolism, and arrhythmias. This article summarizes the various cardiovascular complications and mechanisms responsible for the same with COVID-19 infection. For the benefit of the scientific community and public, the effect of COVID-19 on major vital organs such as the kidneys, liver, and intestines has been briefly discussed. In this review, we also discuss drugs in different stages of clinical trials and their associated complications, as well as the details of vaccines in various stages of development.

Current and novel therapeutic targets in the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA), a multifactorial disease characterized by synovitis, cartilage destruction, bone erosion, and periarticular decalcification, finally results in impairment of joint function. Both genetic and environmental factors are risk factors in the development of RA. Unwanted side effects accompany most of the current treatment strategies, and around 20-40% of patients with RA do not clinically benefit from these treatments. The unmet need for new treatment options for RA has prompted research in the development of novel agents acting through physiologically and pharmacologically relevant targets. Here we discuss in detail three critical pathways, Janus kinase/signal transducer and activator of transcription (JAK/STAT), Th17, and hypoxia-inducible factor (HIF), and their roles as unique therapeutic targets in the field of RA. Some of the less developed but potential targets like nucleotide-binding and oligomerization domain-like receptor containing protein 3 (NLRP3) inflammasome and histone deacetylase 1 (HDAC1) are also discussed.

Fructose-palmitate based high calorie induce steatosis in HepG2 cells via mitochondrial dysfunction: An in vitro approach.

A proper in vitro model for conducting research on high energy food induced steatosis via defective energy metabolism in the liver is not visible in the literature. The present study developed an in vitro model in HepG2 cell line to mimic high energy diet induced steatosis in liver via mitochondrial dysfunction. For this, HepG2 cells were treated with fructose (100 mM) and palmitate (100 µM) for about 24 h and subjected for biochemical analysis relevant to lipogenesis and mitochondrial biology. Our findings showed that fructose-palmitate treatment caused significant lipid accumulation and rise in lipogenic proteins. Further studies showed alteration in mitochondrial integrity, dynamics and oxidative phosphorylation. Mitochondrial integrity was affected by the dissipation of trans-membrane potential, surplus mitochondrial superoxide with calcium overload. Similarly, mitochondrial dynamics were altered with up regulation of mitochondrial fission proteins: DRP1 and FIS1, cytochrome c release, caspase-3 activity and apoptosis. Various components of the electron transport chain: complex I, II, III and IV were altered with significant depletion in oxygen consumption. Overall our findings illustrate the dominant role of mitochondria in the genesis of high fructose-palmitate induced steatosis in HepG2 cells. Since continuous high energy food consumption is the main inducer of steatosis, this model is found to be an ideal one for preliminary and basic research in the area of liver disease via mitochondrial dysfunction.

Pretreatment of Tribulus terrestris L. causes anti-ischemic cardioprotection through MAPK mediated anti-apoptotic pathway in rat.

The aim of the present investigation is the evaluation and elucidation of the mechanisms by which Tribulus terrestris L. methanol extract (TTM) devoid of fruit exhibits protection against cardiac ischemia in in vitro (H9c2 cell line) and in vivo (Wistar rat) model. Tribulus terrestris L. (TT) was used in this study to evaluate the efficacy against cardiac ischemia employing in vitro and in vivo models of myocardial ischemia. H9c2 cells were used for the in vitro induction of ischemia. Male Wistar rats (10 weeks old) weighing 180-220 g were used for the in vivo experiments. ECG and clinically relevant cardiac biomarkers like serum lactate dehydrogenase, serum creatinine kinase, serum creatinine kinase myocardial B fraction, serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase were analysed to evaluate efficacy in the rat. For elucidation of molecular mechanisms of its beneficial activity in vitro, expression of apoptotic markers like Bax, Bad, Bcl-2 and signalling pathways involving mitogen-activated protein kinases like p38α, JNK, and Akt were studied. Tribulus terrestris L. was found effective against cardiac ischemia in the rat which was evident from ECG and various cardiac biomarkers analysis. Tribulus terrestris L. was found to act through the mitogen-activated signalling pathway leading to prevention of apoptosis during ischemic insult. The beneficial effect of Tribulus terrestris L. against cardiac ischemia was seen both in in vitro and in vivo models via its anti-apoptotic potential.

Glucotoxicity results in apoptosis in H9c2 cells via alteration in redox homeostasis linked mitochondrial dynamics and polyol pathway and possible reversal with cinnamic acid.

Several mechanisms have been proposed for the heart dysfunction during hyperglycemia. The aim of the present in vitro study is to elucidate the role of alterations in redox homeostasis in the induction of apoptosis during hyperglycemia in H9c2 cells via dysfunction in mitochondria and polyol pathway and evaluation of the beneficial effect of cinnamic acid against the same. The H9c2 cells were incubated with 33 mM glucose for 48 h to simulate the diabetic condition. Cell injury was confirmed with a significant increase of atrial natriuretic peptide and lactate dehydrogenase release. Alterations in the innate antioxidant system, polyol pathway, mitochondrial integrity, dynamics and apoptosis were investigated. Hyperglycemic insult has significantly affected redox homeostasis via depletion of superoxide dismutase, glutathione and enhanced reactive oxygen species generation. It also caused dysregulation in mitochondrial dynamics (fusion, fission proteins), dissipation of mitochondrial transmembrane potential and increased sorbitol accumulation. Finally, apoptosis was observed with upregulation of Bax, activation of caspase-3 and downregulation of Bcl-2. Cinnamic acid cotreatment increased the innate antioxidant status, improved mitochondrial function and prevented apoptosis in H9c2 cardiomyoblasts. Moreover, this in vitro model is found to be ideal for the elucidation of mechanisms at the cellular and molecular level of any physiological, pharmacological and toxicological incidents in H9c2 cells.

Chlorogenic acid attenuates glucotoxicity in H9c2 cells via inhibition of glycation and PKC α upregulation and safeguarding innate antioxidant status.

A series of cardiovascular complications associated with hyperglycemia is a critical threat to the diabetic population. Here we elucidate the link between hyperglycemia and cardiovascular diseases onset, focusing on oxidative stress and associated cardiac dysfunctions. The contribution of advanced glycation end products (AGE) and protein kinase C (PKC) signaling is extensively studied. For induction of hyperglycemia, H9c2 cells were incubated with 33 mM glucose for 48 h to simulate the diabetic condition in in vitro system. Development of cardiac dysfunction was confirmed with the significant increase of lactate dehydrogenase (LDH) release to the medium and associated decrease in cell viability. Various parameters like free radical generation, alteration in innate antioxidant system, lipid peroxidation, AGE production and PKC α -ERK axis were investigated during hyperglycemia and with chlorogenic acid. Hyperglycemia has significantly enhanced reactive oxygen species (ROS- 4 fold) generation, depleted SOD activity (1.3 fold) and expression of enzymes particularly CuZnSOD (SOD1) and MnSOD (SOD2), increased production of AGE (2.18 fold). Besides, PKC α dependent ERK signaling pathway was found activated (1.43 fold) leading to cardiac dysfunction during hyperglycemia. Chlorogenic acid (CA) was found beneficial against hyperglycemia most probably through its antioxidant mediated activity. The outcome of this preliminary study reveals the importance of integrated approach emphasizing redox status, glycation and signaling pathways like PKC α - ERK axis for control and management of diabetic cardiomyopathy (DCM) and potential of bioactives like CA.

Selenium incorporated guar gum nanoparticles safeguard mitochondrial bioenergetics during ischemia reperfusion injury in H9c2 cardiac cells.

The application of nanotechnology has created high impact in diagnosis and prognosis of various disorders including cardiovascular diseases. In the present study, we investigated the beneficial effect of selenium incorporated guar gum nanoparticles (SGG) compared to nascent selenium (Se) and guar gum nanoparticles (GGN) against ischemiareperfusion (IR) induced alterations in oxidative phosphorylation and energy metabolism in H9c2 cardiac cells. Ischemia and reperfusion were induced for 1h. The alterations in activities of various complexes (complex 1, II, III and IV) of mitochondrial electron transport chain (ETC), aconitase activity, oxygen consumption rate, and the ATP content were seen. The role of heat shock protein, hypoxia inducible factor-1α and atrial natriuretic factor (ANP) were also analyzed. Then the beneficial properties of various particles like Se, GGN and SGG were evaluated. Among these, SGG treatment (1 and 5ng) was found to be more beneficial compared to other particles. Overall results reveal that SGG nanoparticles are effective in protecting H9c2 cardiac cells from IR injury via improving the efficiency of ETC in H9c2 cells.