Understanding long COVID myocarditis: A comprehensive review.

Infectious diseases are a cause of major concern in this twenty-first century. There have been reports of various outbreaks like severe acute respiratory syndrome (SARS) in 2003, swine flu in 2009, Zika virus disease in 2015, and Middle East Respiratory Syndrome (MERS) in 2012, since the start of this millennium. In addition to these outbreaks, the latest infectious disease to result in an outbreak is the SARS-CoV-2 infection. A viral infection recognized as a respiratory illness at the time of emergence, SARS-CoV-2 has wreaked havoc worldwide because of its long-lasting implications like heart failure, sepsis, organ failure, etc., and its significant impact on the global economy. Besides the acute illness, it also leads to symptoms months later which is called long COVID or post-COVID-19 condition. Due to its ever-increasing prevalence, it has been a significant challenge to treat the affected individuals and manage the complications as well. Myocarditis, a long-term complication of coronavirus disease 2019 (COVID-19) is an inflammatory condition involving the myocardium of the heart, which could even be fatal in the long term in cases of progression to ventricular dysfunction and heart failure. Thus, it is imperative to diagnose early and treat this condition in the affected individuals. At present, there are numerous studies which are in progress, investigating patients with COVID-19-related myocarditis and the treatment strategies. This review focuses primarily on myocarditis, a life-threatening complication of COVID-19 illness, and endeavors to elucidate the pathogenesis, biomarkers, and management of long COVID myocarditis along with pipeline drugs in detail.

Sesamol attenuates bleomycin-induced pulmonary toxicity and fibrosis in experimental animals.

Sesamol, a lignan obtained from roasted seeds of Sesamum indicum, has high antioxidant and anti-inflammatory activity. In this study, we have investigated the effect of sesamol on Bleomycin (BLM) induced pulmonary toxicity as well as fibrosis in Wistar rats. Lung toxicity was induced by administration of BLM, 0.015 U/g ip, twice weekly for 28 days whereas lung fibrosis was induced by BLM, 0.015 U/g ip, every 5th day for 49 days. Sesamol administration was started 7 days before first dose of BLM in both the models. It was observed that sesamol 50 mg/kg most effectively attenuated pulmonary toxicity by reducing oxidative stress, inflammation and apoptosis. This dose was further evaluated for its anti-fibrotic effect. It was observed that there was a significant reduction in fibrosis. Lung collagen content was markedly reduced. Furthermore, expression of pro-fibrotic proteins, TGF-ß/SMAD and α-SMA, was reduced and that of anti-fibrotic protein, AMPK, was markedly increased. Even though the combination of sesamol with pirfenidone exhibited no additional protection than either drug alone, it is evident from our study that our test drug, sesamol is comparable in efficacy to pirfenidone. Thus, sesamol has promising therapeutic potential in treatment of pulmonary toxicity and fibrosis.

Evidence-based mechanistic role of chrysin towards protection of cardiac hypertrophy and fibrosis in rats.

Cardiac hypertrophy is the enlargement of cardiomyocytes in response to persistent release of catecholamine which further leads to cardiac fibrosis. Chrysin, flavonoid from honey, is well known for its multifarious properties like antioxidant, anti-inflammatory, anti-fibrotic and anti-apoptotic. To investigate the cardioprotective potential of chrysin against isoproterenol (ISO), cardiac hypertrophy and fibrosis are induced in rats. Acclimatised male albino Wistar rats were divided into seven groups (n 6): normal (carboxymethyl cellulose at 0·5 % p.o.; as vehicle), hypertrophy control (ISO 3 mg/kg, s.c.), CHY15 + H, CHY30 + H & CHY60 + H (chrysin; p.o.15, 30 and 60 mg/kg respectively + ISO at 3 mg/kg, s.c.), CHY60 (chrysin 60 mg/kg in per se) and LST + H (losartan 10 mg/kg p.o. + ISO 3 mg/kg, s.c.) were treated for 28 d. After the dosing schedule on day 29, haemodynamic parameters were recorded, after that blood and heart were excised for biochemical, histological, ultra-structural and molecular evaluations. ISO administration significantly increases heart weight:body weight ratio, pro-oxidants, inflammatory and cardiac injury markers. Further, histopathological, ultra-structural and molecular studies confirmed deteriorative changes due to ISO administration. Pre-treatment with chrysin of 60 mg/kg reversed the ISO-induced damage to myocardium and prevent cardiac hypertrophy and fibrosis through various anti-inflammatory, anti-apoptotic, antioxidant and anti-fibrotic pathways. Data demonstrated that chrysin attenuated myocardial hypertrophy and prevented fibrosis via activation of transforming growth factor-beta (TGF-ß)/Smad signalling pathway.

Cardioprotective effects of azilsartan compared with that of telmisartan on an in vivo model of myocardial ischemia-reperfusion injury.

Azilsartan is found to be more potent than other angiotensin receptor blockers in reducing blood pressure. However, its effect on the heart following myocardial infarction remains to be established. For the first time, we investigated the peroxisome proliferator-activated receptor-γ (PPAR-γ) agonistic and cardioprotective properties of azilsartan. Computational modeling studies of interactions between azilsartan and PPAR-γ revealed azilsartan as an agonist of PPAR-γ and showed the mechanism of azilsartan in cardioprotection. Our study compared the cardioprotective potential of telmisartan to that of azilsartan in a murine model of myocardial ischemia-reperfusion injury by comparing their antioxidant, ant apoptotic, anti-inflammatory, mitogen-activated protein kinase (MAPK)-modulating ability, and PPAR-γ agonistic activity. Male Wistar rats were grouped into four to receive vehicle (dimethyl sulfoxide [0.05%] 2 ml/kg) telmisartan (10 mg/kg p.o.), azilsartan (10 mg/kg p.o.) or azilsartan with specific PPAR-γ blocker, GW 9662 for 28 days. Ischemia was induced for 45 min on the 29th day followed by 60 min of reperfusion. Telmisartan and azilsartan pretreatment significantly nearly normalized cardiac parameters and preserved structural changes. Both drugs inhibited oxidative burst, inflammation, as well as cell death by modulating apoptotic protein expression along with reduction in 4',6-diamidino-2-phenylindole/terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. An increment in pro-survival kinase ERK paralleled with a reduction in p38 and JNK was also revealed by MAPK pathway studies, after administration of these drugs. Interestingly, the aforementioned changes induced by both drugs were reversed by administration of the specific PPAR-γ antagonist, GW9662. However, we found that azilsartan upregulated PPAR-γ to a lesser extent as compared to telmisartan and the latter may be preferred in hypertensive patients at risk of myocardial infarction.

Targeting AGE-RAGE signaling pathway by Saxagliptin prevents myocardial injury in isoproterenol challenged diabetic rats.

The role of Saxagliptin in diabetes-associated cardiovascular complications is controversial. This study aimed to investigate whether Saxagliptin could prevent Isoproterenol-induced myocardial changes in diabetic rats and to identify the possible mechanism as well. The high-fat diet/low-dose Streptozotocin-induced type 2 diabetic rats were divided into 3 groups: the control group (0.25% CMC for 28 days), the Isoproterenol group (85 mg/kg Isoproterenol for the last 2 days plus 0.25% CMC for 28 days), and the treatment group (10 mg/kg Saxagliptin for 28 days plus 85 mg/kg Isoproterenol for the last 2 days). Hemodynamic measurements were performed, and samples were examined for RAGE and NF-κB expressions, histopathological and ultrastructural changes, AGEs level, myocardial injury markers, oxidative stress, and apoptosis. Saxagliptin significantly recovered cardiac function (p < .001), reverted myocardial injury and oxidative stress levels back to the control value (p < .05 to p < .001). Saxagliptin alleviates Isoproterenol-induced myocardial injury in diabetic rats by suppressing AGE-RAGE pathway.

The molecular mechanism involved in cardioprotection by the dietary flavonoid fisetin as an agonist of PPAR-γ in a murine model of myocardial infarction.

The methodology exploring the cardioprotective potential of the flavonoid Fisetin through its ability to modulate PPAR-γ was unraveled in the present study. Computational modelling through molecular docking based binding study of interactions between Fiestin and PPAR-γ revealed the potential role of Fisetin as an agonist of PPAR-γ. A murine model of cardiac ischemia-reperfusion injury was used to explore this further. Male Wistar Rats were randomly assigned to five groups. Fisetin (20 mg/kg; p. o) was administered for 28 days. Ischemia was induced for 45 min on the 29th day followed by 60 min of reperfusion. Fisetin pretreatment upregulated the expression of PPAR-γ in heart tissue significantly Cardioprotection was assessed by measurement of hemodynamic parameters, infarct size, ELISA for oxidative stress, immunohistochemistry and TUNEL assay for apoptosis, and western blot analysis for MAPK proteins and inflammation. PPAR-γ activation by fisetin led to significantly reduced infarct size, suppression of oxidative stress, reduction of cardiac injury markers, alleviation of inflammation, and inhibition of apoptosis The MAPK-based molecular mechanism showed a rise in a key prosurvival kinase, ERK1/ERK2 and suppression of JNK and p38 proteins. The aforementioned beneficial findings of fisetin were reversed on the administration of a specific antagonist of PPAR-γ. In conclusion, through our experiments, we have proved that fisetin protects the heart against ischemia-reperfusion injury and the evident cardioprotection is PPAR-γ dependant. In conclusion, our study has revealed a prime mechanism involved in the cardioprotective effects of fisetin. Hence, Fisetin may be evaluated in further clinical studies as a cardioprotective agent in patients undergoing reperfusion interventions.

Erdosteine salvages cardiac necrosis: Novel effect through modulation of MAPK and Nrf-2/HO-1 pathway.

Isoproterenol (ISO) induced oxidative stress and inflammation is involved in the pathogenesis of myocardial necrosis. To optimize the effect of erdosteine against myocardial necrosis, male albino Wistar rats were divided into eight groups (n = 6), that is, normal, ISO-control, erdosteine pretreatment with ISO. Rats were administered erdosteine orally for 28 days. Two doses of ISO (85 mg/kg), s.c. were given to ISO-C and erdosteine treatment groups on the 27th and 28th day. On the 29th day, hemodynamic parameters were recorded and the heart was excised for further parameters. In ISO-C rats, significantly increased levels of inflammatory markers, pro-oxidants, and structural damage were observed as compared with normal group. Furthermore, immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling revealed an increased expression of apoptotic proteins. Erdosteine at 80 mg/kg reversed the deleterious effects of ISO and normalized myocardium. Erdosteine showed anti-inflammatory, antiapoptotic, and antioxidant activities through inhibition of MAPK and Nrf-2/HO-1 pathways. To conclude, erdosteine was found protective in ISO-induced myocardial necrosis through MAPK and Nrf-2/HO-1 pathway.

The dietary isoflavone daidzein mitigates oxidative stress, apoptosis, and inflammation in CDDP-induced kidney injury in rats: Impact of the MAPK signaling pathway.

Cisplatin-induced nephrotoxicity persists as a clinical problem despite several supportive measures to alleviate renal damage. Daidzein (DZ), a dietary isoflavone having antioxidant and anti-inflammatory activity, is investigated in this study for protective effects against cisplatin-induced renal injury in rats. DZ (25, 50, or 100 mg/kg; intraperitoneally; 10 days) was administered along with Cisplatin, single dose, on the 7th day of the experiment. On the 11th day, the rats were euthanized, and different samples were collected for analysis. Biochemical, histopathological, and molecular parameters were assessed to evaluate the effect of daidzein. Cisplatin injection resulted in renal dysfunction, lipid peroxidation that led to consumption of antioxidants, exaggerated apoptosis, and inflammation. These changes were associated with increase in the signaling proteins. DZ attenuated the toxic effects of cisplatin on the kidney at 100 mg/kg dose. The study concludes with the finding that daidzein imparts protection against the nephrotoxic effect of Cisplatin and can be considered as a novel, potential therapy.

Mangiferin attenuates cisplatin-induced acute kidney injury in rats mediating modulation of MAPK pathway.

Cisplatin has been confined due to the reported cases of nephrotoxicity. In the present study, an active xanthone, Mangiferin (from Mangifera indica) was investigated for its defensive role in cisplatin-induced nephrotoxicity. Male wistar albino rats were divided into six groups i.e., group 1 (normal); group 2 (cisplatin control); group 3, 4, and 5 (mangiferin 10, 20, and 40 mg/kg, i.p.); and per se (40 mg/kg; i.p.). The treatment was given for 10 days. On day 7, single dose of cisplatin 8 mg/kg i.p. was administered to induce nephrotoxicity in all groups except normal and per se. On day 11, animals were anesthetized, blood was taken from heart and serum was separated. Thereafter, rats were sacrificed and kidneys were isolated and preserved for histopathological, ultrastructural, immunohistochemical, and western blot analysis. Cisplatin control group showed significant impairment in renal function due to increased inflammation and oxidative stress which was also confirmed by histopathology and MAPK pathway proteins expression. However, pretreatment with mangiferin 20 and 40 mg/kg significantly reversed the renal function along with the structural changes and the levels of antioxidants. Mangiferin treatment attenuated DNA damage and apoptotic pathway.

Role of MAPK/NF-κB pathway in cardioprotective effect of Morin in isoproterenol induced myocardial injury in rats.

Oxidative stress plays a major role in myocardial injury. Morin, a bioflavonoid has known to possess various biological activities in previous studies. Hence, this study evaluated the cardioprotective mechanism(s) of Morin against isoproterenol induced myocardial necrosis in rats. Male albino Wistar rats were divided into five groups (n = 8) i.e., I (normal), II (ISO-control), III, IV and V (morin 20, 40 and 80 mg/kg respectively). Groups III, IV and V were treated orally with daily doses of Morin accordingly for 28 days. On 26th and 27th day, a single injection of isoproterenol was injected (85 mg/kg s.c.) at 24 h interval to induce myocardial necrosis in group II, III, IV and V. On 28th day, hemodynamic parameters were evaluated, animals were euthanised and heart was excised for measurement of various parameters. In ISO-control rats, there was deterioration of hemodynamic parameters, decreased anti-oxidants levels, increased cardiac injury markers and pro-inflammatory cytokines (TNF-α and IL-6). Also, there was increased level of Bax, Caspase-3, p-JNK, p-38 and NF-κB and decreased expression of Bcl-2 and p-ERK1/2 in ISO-C group. Morin dose-dependently improved hemodynamic profile, increased anti-oxidant levels, normalized myocardial architecture and reduced inflammatory markers and apoptosis. Furthermore, immunoblot analysis of MAPK pathway proteins demonstrated the mechanism responsible for anti-apoptotic and anti-inflammatory potential of morin. Thus, this study substantiated the beneficial effect of Morin by virtue of its modulation of MAPK pathway in myocardial injury.

Hesperidin regresses cardiac hypertrophy by virtue of PPAR-γ agonistic, anti-inflammatory, antiapoptotic, and antioxidant properties.

Hesperidin (HES), a flavanone glycoside, predominant in citrus fruits, has an agonistic activity on peroxisome proliferator-activated receptor gamma (PPAR-γ). PPAR-γ is an inhibitor of cardiac hypertrophy (CH) signaling pathways. In this study, we investigated the cardioprotective effect of HES in isoproterenol (ISO)-induced CH through PPAR-γ agonistic activity. For this, male albino Wistar rats were divided into six groups (n = 6), that is, normal, ISO-control, HES treatment group (200 mg kg-1 ; p.o.), HES per se (200 mg kg-1 ; p.o.), enalapril treatment group (30 mg kg-1 ; p.o.), and combination group (HES 200 mg kg-1 ; p.o.+enalapril 30 mg kg-1 ; p.o.). ISO (3 mg kg-1 ; s.c.) was administered to all groups except normal and per se to induce CH. HES or enalapril treatment of 28 days significantly attenuated pathological changes, improved cardiac hemodynamics, suppressed oxidative stress, and apoptosis along with an increased PPAR-γ expression. The combination of enalapril with HES exhibited an effect similar to that of HES or enalapril alone on all the aforementioned parameters. Therefore, HES may be further evaluated as a promising molecule for the alleviation of CH.

E-selectin gene in essential hypertension: a case-control study.

BACKGROUND: Hypertension is associated with endothelial cell dysfunction. E-selectin, an endothelial cell adhesion molecule, is specific for endothelial cell activation. Polymorphism in E-selectin gene has recently been identified among which Leu554Phe E-selectin gene polymorphism is least investigated in essential hypertension. This study reports the association of E-selectin gene Leu554Phe polymorphism and the expression of E-selectin gene in patients with essential hypertension. MATERIALS AND METHODS: We analysed the Leu554Phe polymorphism and expression of E-selectin gene in 250 patients with essential hypertension and 250 normal healthy controls. Genotyping of Leu554Phe polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the expression of E-selectin gene at mRNA and protein levels were carried out by real-time PCR and Western blot, respectively. RESULTS: A significant association of E-selectin genotypes (CT + TT) with essential hypertension (P < .0001, Odds ratio = 2.2 [1.58-3.24] at 95% CI) was observed. The expression of mRNA for E-selectin gene in patients with essential hypertension was ~12-fold higher as compared to control. We observed an elevated level of E-selectin protein expression (up to 1.9 times) in patients as compared to controls. CONCLUSIONS: A significant association of E-selectin (Leu554Phe) gene and increased expression of E-selectin gene at mRNA and protein levels in patients might be related to the genetic predisposition to develop essential hypertension.

Apigenin ameliorates streptozotocin-induced diabetic nephropathy in rats via MAPK-NF-κB-TNF-α and TGF-ß1-MAPK-fibronectin pathways.

Diabetic nephropathy (DN), a microvascular complication of diabetes, has emerged as an important health problem worldwide. There is strong evidence to suggest that oxidative stress, inflammation, and fibrosis play a pivotal role in the progression of DN. Apigenin has been shown to possess antioxidant, anti-inflammatory, antiapoptotic, antifibrotic, as well as antidiabetic properties. Hence, we evaluated whether apigenin halts the development and progression of DN in streptozotocin (STZ)-induced diabetic rats. Male albino Wistar rats were divided into control, diabetic control, and apigenin treatment groups (5-20 mg/kg po, respectively), apigenin per se (20 mg/kg po), and ramipril treatment group (2 mg/kg po). A single injection of STZ (55 mg/kg ip) was administered to all of the groups except control and per se groups to induce type 1 diabetes mellitus. Rats with fasting blood glucose >250 mg/dl were included in the study and randomized to different groups. Thereafter, the protocol was continued for 8 mo in all of the groups. Apigenin (20 mg/kg) treatment attenuated renal dysfunction, oxidative stress, and fibrosis (decreased transforming growth factor-ß1, fibronectin, and type IV collagen) in the diabetic rats. It also significantly prevented MAPK activation, which inhibited inflammation (reduced TNF-α, IL-6, and NF-κB expression) and apoptosis (increased expression of Bcl-2 and decreased Bax and caspase-3). Furthermore, histopathological examination demonstrated reduced inflammation, collagen deposition, and glomerulosclerosis in the renal tissue. In addition, all of these changes were comparable with those produced by ramipril. Hence, apigenin ameliorated renal damage due to DN by suppressing oxidative stress and fibrosis and by inhibiting MAPK pathway.

Molecular Pathways Involved in the Amelioration of Myocardial Injury in Diabetic Rats by Kaempferol.

There is growing evidence that chronic hyperglycemia leads to the formation of advanced glycation end products (AGEs) which exerts its effect via interaction with the receptor for advanced glycation end products (RAGE). AGE-RAGE activation results in oxidative stress and inflammation. It is well known that this mechanism is involved in the pathogenesis of cardiovascular disease in diabetes. Kaempferol, a dietary flavonoid, is known to possess antioxidant, anti-apoptotic, and anti-inflammatory activities. However, little is known about the effect of kaempferol on myocardial ischemia-reperfusion (IR) injury in diabetic rats. Diabetes was induced in male albino Wistar rats using streptozotocin (70 mg/kg; i.p.), and rats with glucose level >250 mg/dL were considered as diabetic. Diabetic rats were treated with vehicle (2 mL/kg; i.p.) and kaempferol (20 mg/kg; i.p.) daily for a period of 28 days and on the 28th day, ischemia was produced by one-stage ligation of the left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed and the heart tissue was processed for biochemical, morphological, and molecular studies. Kaempferol pretreatment significantly reduced hyperglycemia, maintained hemodynamic function, suppressed AGE-RAGE axis activation, normalized oxidative stress, and preserved morphological alterations. In addition, there was decreased level of inflammatory markers (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and NF-κB), inhibition of active c-Jun N-terminal kinase (JNK) and p38 proteins, and activation of Extracellular signal regulated kinase 1/2 (ERK1/2) a prosurvival kinase. Furthermore, it also attenuated apoptosis by reducing the expression of pro-apoptotic proteins (Bax and Caspase-3), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells, and increasing the level of anti-apoptotic protein (Bcl-2). In conclusion, kaempferol attenuated myocardial ischemia-reperfusion injury in diabetic rats by reducing AGE-RAGE/ mitogen activated protein kinase (MAPK) induced oxidative stress and inflammation.

Molecular mechanisms underlying attenuation of cisplatin-induced acute kidney injury by epicatechin gallate.

Cisplatin, a platinum compound, is used as a first-line agent against various forms of solid cancers. Nephrotoxicity is an important adverse effect of cisplatin therapy, which involves increased oxidative stress, inflammation, apoptosis, and activation of the mitogen-activated protein kinase (MAPK) pathway. It is well known that the bioactive compounds present in green tea are used to treat various disorders due to their biological activities. With this background, the present study was aimed to investigate the effect of epicatechin gallate (ECG), a green tea polyphenol, in cisplatin-induced nephrotoxicity in rats. To achieve this, ECG (1.25, 2.5, and 5 mg/kg; intraperitoneal (i.p.)) was administered to male albino Wistar rats for the period of 10 days. On the 7th day, a single i.p. injection of cisplatin (8 mg/kg) was injected into rats to produce kidney injury and the animals were then killed on the 10th day. Cisplatin toxicity was associated with enhanced oxidative stress, impaired renal function along with marked tubular necrosis in Histopathology. Furthermore, cisplatin activated the MAPK pathway, which contributed to inflammation and apoptosis in the kidney of treated rats. In contrast, ECG (5 mg/kg) pretreatment normalized cisplatin-induced oxidative stress, renal function, and histopathological changes. ECG also prevented the activation of the MAPK pathway, and attenuated inflammation and apoptosis in rats. These findings suggest that ECG prevented cisplatin-induced oxidative stress, inflammation, and apoptosis by downregulating the MAPK pathway and resulted in improved renal function.

5-HT2B receptor blockade attenuates ß-adrenergic receptor-stimulated myocardial remodeling in rats via inhibiting apoptosis: role of MAPKs and HSPs.

Recent studies have proposed the potential role of 5-HT2B receptor (5-HT2BR) blockade in alleviating myocardial dysfunction; hitherto, the regulatory pathway for its protective effect has remained enigmatic. In the present study, we sought to investigate the role of SB-204741, a 5-HT2BR blocker in isoproterenol-induced myocardial remodeling in rats and its cross-talk with apoptosis and mitogen activated protein kinase (MAPKs)/heat shock proteins (HSPs) pathway. To assess this hypothesis, we measured the effect of SB-204741 (0.25-1.0 mg/kg/day, i.p.) in isoproterenol (85 mg/kg/day, s.c.)-induced myocardial remodeling in rats. SB-204741 dose dependently improved hemodynamic and ventricular functions following isoproterenol-induced myocardial injury. This amelioration was well substantiated with reduced expression of 5-HT2B, inflammatory proteins (NF-κBp65, IKK-ß, TNF-α, IL-6, and Cox-2), MAPKs (p-p38/p38 and p-JNK/JNK ratio) accompanied with increased protein expression of HSPs (αB-crystallin, Hsp27 and Hsp70), autophagy (LC3 and Beclin-1) and p-ERK/ERK ratio. Additionally, SB-204741 inhibited apoptotic signaling pathway as there was decreased DAPI/TUNEL positivity and protein expression of cytochrome c, Bax, and caspase-3 along with increased Bcl-2 expression. Preservation of histopathological and ultrastructural components, normalization of nitric oxide level, endogenous antioxidants and myocyte injury marker enzymes were also observed. In conclusion, inhibition of apoptosis via modulation of MAPKs/HSPs is essential for 5-HT2BR blockade mediated cardioprotective effect.

Licorice treatment prevents oxidative stress, restores cardiac function, and salvages myocardium in rat model of myocardial injury.

The present study examined the effects of licorice on antioxidant defense, functional impairment, histopathology, and ultrastructural alterations in isoproterenol (ISP)-induced myocardial injury in rats. Myocardial necrosis was induced by two subcutaneous injection of ISP (85 mg/kg) at an interval of 24 h. Licorice was administered orally for 30 days in the doses of 100, 200, 400, or 800 mg/kg. ISP-treated rats showed impaired hemodynamics, left ventricular dysfunction, and caused depletion of antioxidants and marker enzymes along with lipid peroxidation from myocardium. ISP also induced histopathological and ultrastructural alterations in myocardium. Pretreatment with licorice prevented the depletion of endogenous antioxidants and myocyte injury marker enzymes, inhibited lipid peroxidation, and showed recovery of hemodynamic and ventricular functions. Licorice treatment also reduced myonecrosis, edema, and infiltration of inflammatory cells and showed preservation of subcellular and ultrastructural components. Our results demonstrate that licorice exerts cardioprotection by reducing oxidative stress, augmenting endogenous antioxidants, and restoring functional parameters as well as maintaining structural integrity.

Expression of angiotensin-converting enzyme gene in whole blood in patients with essential hypertension.

OBJECTIVE: The present study aims to investigate the correlation of the angiotensin-converting enzyme (ACE) gene expression and protein expression in patients with essential hypertension in whole blood. METHODS: ACE gene expression was analyzed by Real Time PCR and western blot in 52 patients with essential hypertension and 42 healthy controls. RESULTS: We observed a significant increase in Delta threshold cycle (ΔCT) values in the circulating ACE gene and ACE protein expression in patients as compared to controls. CONCLUSIONS: The up-regulation in relative expression of circulating Angiotensin converting enzyme mRNA and protein in patients with respect to controls might be correlated with high blood pressure in patients with essential hypertension.

Naringin ameliorates pentylenetetrazol-induced seizures and associated oxidative stress, inflammation, and cognitive impairment in rats: possible mechanisms of neuroprotection.

Oxidative stress and cognitive impairment are associated with PTZ-induced convulsions. Naringin is a bioflavonoid present in the grapefruit. It is a potent antioxidant, and we evaluated its effect on PTZ-induced convulsions. Rats were pretreated with normal saline, naringin (20, 40, and 80 mg/kg, i.p.), or diazepam (5mg/kg, i.p.) 30 min prior to the administration of PTZ. The administration of PTZ induced myoclonic jerks and generalized tonic-clonic seizures (GTSs). We observed that naringin significantly prolonged the induction of myoclonic jerks dose-dependently. Naringin (80 mg/kg, i.p.) pretreatment protected all rats, and this protective effect was annulled by the GABAA receptor antagonist, flumazenil. In addition, naringin reduced brain MDA and TNF-α levels and conserved GSH. The pretreatment also enhanced the performance of rats in the passive avoidance task. Our observations highlight the antioxidant, antiinflammatory, and anticonvulsant potential of naringin. Also, naringin modulates the GABAA receptor to produce anticonvulsant effects and to ameliorate cognitive impairment.

Molecular mechanisms of flavonoids in myocardial ischemia reperfusion injury: Evidence from in-vitro and in-vivo studies.

OBJECTIVES: Flavonoids are polyphenolic compounds found in a wide range of foods, including fruits, vegetables, tea plants, and other natural products. They have been mainly classified as flavanols, flavonols, flavones, isoflavones, flavanones, and flavanonols. In this comprehensive review, we will discuss preclinical pieces of evidence on the potential of flavonoids for the prevention/treatment of myocardial ischemia-reperfusion (IR) injury. KEY FINDINGS: In-vitro and in-vivo studies have shown that flavonoids play an important role in preventing ischemic heart disease (IHD). They possess strong anti-oxidant, anti-inflammatory, anti-bacterial, anti-thrombotic, anti-apoptotic, and anti-carcinogenic activities. In addition, at a molecular level, flavonoids also modulate various pathways like MAPK, NFκB etc. to confer beneficial effects. SUMMARY: The current review of flavonoids in myocardial ischemia-reperfusion injury furnishes updated information that could drive future research. The in-vitro and in-vivo experiments have demonstrated various favourable pharmacological properties of flavonoids. This review provides valuable information to conduct clinical studies, validating the safety aspects of flavonoids in the clinical domain.