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Gynura procumbens (GP) grows abundantly in Southeast Asia. The present work was conducted to investigate the cardioprotective potential of ethanol extract of GP on cardiac markers, antioxidant levels, and histopathology of isoproterenol-induced myocardial infarction (MI). A total of 36 adult Sprague-Dawley rats were randomly divided into six groups. Treatments were given via oral gavage for 28 days: two groups were given normal saline 0.9%; two groups were given GP250 mg/kg/day- and two groups were given GP500 mg/kg/day. On day 27 and 28, MI was induced with a subcutaneous injection of 85 mg/kg isoproterenol. The rats were sacrificed 48 h after the 1st injection. Cardiac markers, lipid peroxidation, oxidative status, and histopathological analyses were evaluated. Isoproterenol significantly increased the levels of troponin T, creatine kinase MB isoenzyme (CKMB), lactate dehydrogenase (LDH), and malondialdehyde (MDA), whereas the level of superoxide dismutase (SOD), catalase, and glutathione peroxidase were significantly decreased. In addition, the histopathological findings showed a necrosis of the myocardium as evidenced by neutrophil infiltration, and interstitial oedema with acceleration of apoptosis in MI. Interestingly, treatment with GP restored the levels of troponin T, LDH, MDA, SOD, and catalase significantly. Moreover, GP preserved the myocardial architecture while decreasing both necrosis and apoptosis. GP has the potential to limit myocardial injury after MI, and this is most likely achieved through its modulation of antioxidant enzyme activities. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is a remarkable chemotherapeutic agent, however, its adverse effect on DOX-induced cardiotoxicity (DIC) is a rising concern. Recent research has identified carvacrol (CAR), an antioxidant and anti-inflammatory agent, as a promising natural compound for protecting against DIC. This study aims to investigate the potential cardioprotective effects properties of CAR in vitro and in vivo. The cardioprotective effect of CAR was assessed by pretreating H9c2 cells with non-toxic CAR for 24 h, followed by co-treatment with DOX (10 μM) for an additional 24 h. The cell viability was determined using an MTT assay. For the in vivo study, male Sprague-Dawley rats (200-250 g) were randomly divided into three groups: control, cardiotoxicity (DOX), and treatment (CAR + DOX) groups. CAR (50 mg/kg, BW) was administered orally to the CAR + DOX groups for 14 days. Then, a single dose of DOX (15 mg/kg/i.p, BW) was administered on day 15 for DOX and CAR + DOX groups. The rats were allowed to recover for 3 days before being sacrificed. Our results demonstrated that DOX (10 µM) significantly reduced H9c2 cell viability by 50% (p < 0.0001), and CAR (0.067 µM) protected H9c2 cells from DIC (p = 0.0045). In the rat model, CAR pretreatment effectively mitigated DOX-induced reductions in systolic pressure (p = 0.0007), pulse pressure (p = 0.0213), hypertrophy (p = 0.0049), and cardiac fibrosis (p = 0.0006). However, the pretreatment did not alter the heart function, oxidative stress, and antioxidant enzymes. In conclusion, our results indicate that CAR could potentially serve as an adjuvant to reduce cardiotoxicity by ameliorating myocardial fibrosis and hypertrophy., Competing Interests: Declarations. Conflicts of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Carvacrol (CA) is a phenolic monoterpene renowned for its diverse pharmacological benefits, particularly its cardioprotective effects. Concurrently, phenolic acids have also demonstrated promise in mitigating drug-induced cardiotoxicity. Focusing on combating doxorubicin-induced cardiotoxicity (DIC), the research aims to synthesize novel cardioprotective agents by combining CA with 3-hydroxybenzoic acid (3HA). Doxorubicin, an anticancer drug, poses cardiovascular risks as its adverse effect, prompting the exploration of hybrid compounds. Various linker molecules, including alkyl and acyl with different carbon lengths, were investigated to understand their impact on bioactivity. In vitro testing on the DOX-induced H9c2 cell death model revealed the effectiveness of a CA conjugate in preserving cardiomyocyte viability. In silico analysis highlighted favorable drug-like properties and low toxicity of the conjugate. This study sheds light on molecular hybridization's potential in developing cardioprotective agents, emphasizing CA's pivotal role in combating DIC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Lupeol, a naturally occurring lupane-type pentacyclic triterpenoid, is widely distributed in various edible vegetables, fruits, and medicinal plants. Notably, it is found in high concentrations in plants like Tamarindus indica , Allanblackia monticola , and Emblica officinalis , among others. Quantitative studies have highlighted its presence in Elm bark, Olive fruit, Aloe leaf, Ginseng oil, Mango pulp, and Japanese Pear bark. This compound is synthesized from squalene through the mevalonate pathway and can also be synthetically produced in the lab, addressing challenges in natural product synthesis. Over the past four decades, extensive research has demonstrated lupeol's multifaceted pharmacological properties, including anti-inflammatory, antioxidant, anticancer, and antibacterial effects. Despite its significant therapeutic potential, clinical applications of lupeol have been limited by its poor water solubility and bioavailability. Recent advancements have focused on nano-based delivery systems to enhance its bioavailability, and the development of various lupeol derivatives has further amplified its bioactivity. This review provides a comprehensive overview of the latest advancements in understanding the pharmacological benefits of lupeol. It also discusses innovative strategies to improve its bioavailability, thereby enhancing its clinical efficacy. The aim is to consolidate current knowledge and stimulate further research into the therapeutic potential of lupeol and its derivatives., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dalimunthe, Carensia Gunawan, Dhiya Utari, Dinata, Halim, Estherina S. Pakpahan, Sitohang, Sukarno, Yuandani, Harahap, Setyowati, Park, Yusoff, Zainalabidin, Prananda, Mahadi, Kim, Harahap and Syahputra.)

Carvacrol, called CA, is a dynamic phytoconstituent characterized by a phenol ring abundantly sourced from various natural reservoirs. This versatile scaffold serves as a pivotal template for the design and synthesis of novel drug molecules, harboring promising biological activities. The active sites positioned at C-4, C-6, and the hydroxyl group (-OH) of CA offer fertile ground for creating potent drug candidates from a pharmacological standpoint. In this comprehensive review, we delve into diverse synthesis pathways and explore the biological activity of CA derivatives. We aim to illuminate the potential of these derivatives in discovering and developing efficacious treatments against a myriad of life-threatening diseases. By scrutinizing the structural modifications and pharmacophore placements that enhance the activity of CA derivatives, we aspire to inspire the innovation of novel therapeutics with heightened potency and effectiveness., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Hypertension, or high blood pressure (BP), is a complex disease influenced by various risk factors. It is characterized by persistent elevation of BP levels, typically exceeding 140/90 mmHg. Endothelial dysfunction and reduced nitric oxide (NO) bioavailability play crucial roles in hypertension development. L-NG-nitro arginine methyl ester (L-NAME), an analog of L-arginine, inhibits endothelial NO synthase (eNOS) enzymes, leading to decreased NO production and increased BP. Animal models exposed to L-NAME manifest hypertension, making it a useful design for studying the hypertension condition. Natural products have gained interest as alternative approaches for managing hypertension. Flavonoids, abundant in fruits, vegetables, and other plant sources, have potential cardiovascular benefits, including antihypertensive effects. Flavonoids have been extensively studied in cell cultures, animal models, and, to lesser extent, in human trials to evaluate their effectiveness against L-NAME-induced hypertension. This comprehensive review summarizes the antihypertensive activity of specific flavonoids, including quercetin, luteolin, rutin, troxerutin, apigenin, and chrysin, in L-NAME-induced hypertension models. Flavonoids possess antioxidant properties that mitigate oxidative stress, a major contributor to endothelial dysfunction and hypertension. They enhance endothelial function by promoting NO bioavailability, vasodilation, and the preservation of vascular homeostasis. Flavonoids also modulate vasoactive factors involved in BP regulation, such as angiotensin-converting enzyme (ACE) and endothelin-1. Moreover, they exhibit anti-inflammatory effects, attenuating inflammation-mediated hypertension. This review provides compelling evidence for the antihypertensive potential of flavonoids against L-NAME-induced hypertension. Their multifaceted mechanisms of action suggest their ability to target multiple pathways involved in hypertension development. Nonetheless, the reviewed studies contribute to the evidence supporting the useful of flavonoids for hypertension prevention and treatment. In conclusion, flavonoids represent a promising class of natural compounds for combating hypertension. This comprehensive review serves as a valuable resource summarizing the current knowledge on the antihypertensive effects of specific flavonoids, facilitating further investigation and guiding the development of novel therapeutic strategies for hypertension management., (© 2024 John Wiley & Sons Ltd.)

Cardiovascular diseases (CVDs) represent a broad spectrum of diseases afflicting the heart and blood vessels and remain a major cause of death and disability worldwide. CVD progression is strongly associated with risk factors, including hypertension, hyperglycemia, dyslipidemia, oxidative stress, inflammation, fibrosis, and apoptosis. These risk factors lead to oxidative damage that results in various cardiovascular complications including endothelial dysfunctions, alterations in vascular integrity, the formation of atherosclerosis, as well as incorrigible cardiac remodeling. The use of conventional pharmacological therapy is one of the current preventive measures to control the development of CVDs. However, as undesirable side effects from drug use have become a recent issue, alternative treatment from natural products is being sought in medicinal plants and is gaining interest. Roselle ( Hibiscus sabdariffa Linn.) has been reported to contain various bioactive compounds that exert anti-hyperlipidemia, anti-hyperglycemia, anti-hypertension, antioxidative, anti-inflammation, and anti-fibrosis effects. These properties of roselle, especially from its calyx, have relevance to its therapeutic and cardiovascular protection effects in humans. This review summarizes the findings of recent preclinical and clinical studies on roselle as a prophylactic and therapeutic agent in attenuating cardiovascular risk factors and associated mechanisms., Competing Interests: The authors declare no conflicts of interest. The funder has no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Doxorubicin (DOX) has been extensively utilized in cancer treatment. However, DOX administration has adverse effects, such as cardiac injury. This study intends to analyze the expression of TGF, cytochrome c, and apoptosis on the cardiac histology of rats induced with doxorubicin, since the prevalence of cardiotoxicity remains an unpreventable problem due to a lack of understanding of the mechanism underlying the cardiotoxicity result. Vernonia amygdalina ethanol extract (VAEE) was produced by soaking dried Vernonia amygdalina leaves in ethanol. Rats were randomly divided into seven groups: K- (only given doxorubicin 15 mg/kgbw), KN (water saline), P100, P200, P400, P4600, and P800 (DOX 15 mg/kgbw + 100, 200, 400, 600, and 800 mg/kgbw extract); at the end of the study, rats were scarified, and blood was taken directly from the heart; the heart was then removed. TGF, cytochrome c, and apoptosis were stained using immunohistochemistry, whereas SOD, MDA, and GR concentration were evaluated using an ELISA kit. In conclusion, ethanol extract might protect the cardiotoxicity produced by doxorubicin by significantly reducing the expression of TGF, cytochrome c, and apoptosis in P600 and P800 compared to untreated control K- ( p < 0.001). These findings suggest that Vernonia amygdalina may protect cardiac rats by reducing the apoptosis, TGF, and cytochrome c expression while not producing the doxorubicinol as doxorubicin metabolite. In the future, Vernonia amygdalina could be used as herbal preventive therapy for patient administered doxorubicin to reduce the incidence of cardiotoxicity.

Cardiac diseases, such as myocardial infarction and heart failure, have become a major clinical problem globally. The accumulating data demonstrate that bioactive compounds with antioxidant and anti-inflammatory properties have favorable effects on clinical problems. Kaempferol is a flavonoid found in various plants; it has demonstrated cardioprotective properties in numerous cardiac injury models. This review aims to collate updated information regarding the effects of kaempferol on cardiac injury. Kaempferol improves cardiac function by alleviating myocardial apoptosis, fibrosis, oxidative stress, and inflammation while preserving mitochondrial function and calcium homeostasis. However, the mechanisms of action of its cardioprotective properties remain unclear; therefore, elucidating its action could provide insight into directions for future studies.

One in every three deaths worldwide is caused by cardiovascular diseases (CVDs), estimating a total of 17.9 million deaths annually. By 2030, it is expected that more than 24 million people will die from CVDs related complications. The most common CVDs are coronary heart disease, myocardial infarction, stroke, and hypertension. A plethora of studies has shown inflammation causing both short-term and long-term damage to the tissues in many organ systems, including the cardiovascular system. In parallel to inflammation processes, it has been discovered that apoptosis, a mode of programmed cell death, may also contribute to CVD development due to the loss of cardiomyocytes. Terpenophenolic compounds are comprised of terpenes and natural phenols as secondary metabolites by plants and are commonly found in the genus Humulus and Cannabis . A growing body of evidence has shown that terpenophenolic compounds exhibit protective properties against inflammation and apoptosis within the cardiovascular system. This review highlights the current evidence elucidating the molecular actions of terpenophenolic compounds in protecting the cardiovascular system, i.e., bakuchiol, ferruginol, carnosic acid, carnosol, carvacrol, thymol and hinokitiol. The potential of these compounds is discussed as the new nutraceutical drugs that may help to decrease the burden of cardiovascular disorders.

Cardiac hypertrophy is an early hallmark during the clinical course of heart failure. Therapeutic strategies aiming to alleviate cardiac hypertrophy via the mitogen-activated protein kinase (MAPK)/calcineurin-nuclear factor of activated T-cells (NFAT) signaling pathway may help prevent cardiac dysfunction. Previously, empty pod ethanol crude extract of Parkia speciosa Hassk was shown to demonstrate protective effects against cardiomyocyte hypertrophy. Therefore, the current study aimed to investigate the effects of various fractions of the plant ethanol extract on the MAPK/NFAT signaling pathway in angiotensin II (Ang II)-induced cardiomyocyte hypertrophy. Simultaneous treatment with ethyl acetate (EA) fraction produced the most potent antihypertrophic effect evidenced by the reduced release of B-type natriuretic peptide (BNP). Subsequently, treatment with the EA fraction (6.25, 12.5, and 25 μg/mL) prevented an Ang II-induced increase in cell surface area, hypertrophic factors (atrial natriuretic peptide and BNP), reactive oxygen species, protein content, and NADPH oxidase 4 expression in the cells. Furthermore, EA treatment attenuated the activation of the MAPK pathway and calcineurin-related pathway (GATA-binding protein 4 and NFATC3), which was similar to the effects of valsartan (positive control). Our findings indicate that the EA fraction prevents Ang II-induced cardiac hypertrophy by regulating the MAPK/calcineurin-NFAT signaling pathway.

Cardiovascular disease (CVD) is directly linked to diabetes mellitus (DM), and its morbidity and mortality are rising at an alarming rate. Individuals with DM experience significantly worse clinical outcomes due to heart failure as a CVD consequence than non-diabetic patients. Hyperglycemia is the main culprit that triggers the activation of oxidative damage, inflammation, fibrosis, and apoptosis pathways that aggravate diabetic CVD progression. In recent years, the development of phytochemical-based nutraceutical products for diabetic treatment has risen due to their therapeutic properties. Anthocyanin, which can be found in various types of plants, has been proposed for preventing and treating various diseases, and has elicited excellent antioxidative, anti-inflammation, anti-fibrosis, and anti-apoptosis effects. In preclinical and clinical studies, plants rich in anthocyanin have been reported to attenuate diabetic CVD. Therefore, the development of anthocyanin as a nutraceutical in managing diabetic CVD is in demand. In this review, we unveil the role of anthocyanin in modulating diabetic CVD, and its potential to be developed as a nutraceutical for a therapeutic strategy in managing CVD associated with DM.

Abstract: Several types of cardiovascular cells use microRNA-21 ( miR-21 ), which has been linked to cardioprotection. In this study, we systematically reviewed the results of published papers on the therapeutic effect of miR-21 for myocardial infarction. Studies described the cardioprotective effects of miR-21 to reduce infarct size by improving angiogenesis, antiapoptotic, and anti-inflammatory mechanisms. Results suggest that cardioprotective effects of miR-21 may work synergistically to prevent the deterioration of cardiac function during postischemia. However, there are other results that indicate that miR-21 positively regulates tissue fibrosis, potentially worsening a postischemic injury. The dual functionalities of miR-21 occur through the targeting of genes and signaling pathways, such as PTEN , PDCD4 , KBTBD7 , NOS3 , STRN , and Spry-1 . This review provides insights into the future advancement of safe miR-21 -based genetic therapy in the treatment of myocardial infarction., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Cardiovascular diseases have become a major clinical burden globally. Heart failure is one of the diseases that commonly emanates from progressive uncontrolled hypertension. This gives rise to the need for a new treatment for the disease. Sacubitril/valsartan is a new drug combination that has been approved for patients with heart failure. This review aims to detail the mechanism of action for sacubitril/valsartan in cardiac remodeling, a cellular and molecular process that occurs during the development of heart failure. Accumulating evidence has unveiled the cardioprotective effects of sacubitril/valsartan on cellular and molecular modulation in cardiac remodeling, with recent large-scale randomized clinical trials confirming its supremacy over other traditional heart failure treatments. However, its molecular mechanism of action in cardiac remodeling remains obscure. Therefore, comprehending the molecular mechanism of action of sacubitril/valsartan could help future research to study the drug's potential therapy to reduce the severity of heart failure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mustafa, Jalil, Zainalabidin, Saleh, Asmadi and Kamisah.)

Cardiovascular disease is the most common cause of death among diabetic patients worldwide. Hence, cardiovascular wellbeing in diabetic patients requires utmost importance in disease management. Recent studies have demonstrated that protein kinase C activation plays a vital role in the development of cardiovascular complications via its activation of mitogen-activated protein kinase (MAPK) cascades, also known as PKC-MAPK pathways. In fact, persistent hyperglycaemia in diabetic conditions contribute to preserved PKC activation mediated by excessive production of diacylglycerol (DAG) and oxidative stress. PKC-MAPK pathways are involved in several cellular responses, including enhancing oxidative stress and activating signalling pathways that lead to uncontrolled cardiac and vascular remodelling and their subsequent dysfunction. In this review, we discuss the recent discovery on the role of PKC-MAPK pathways, the mechanisms involved in the development and progression of diabetic cardiovascular complications, and their potential as therapeutic targets for cardiovascular management in diabetic patients.

Diabetes-induced vascular disorder is considered one of the deadly risk factors among diabetic patients that are caused by persistent hyperglycemia that eventually leads to cardiovascular diseases. Elevated reactive oxygen species (ROS) due to high blood glucose levels activate signaling pathways such as AGE/RAGE, PKC, polyol, and hexosamine pathways. The activated signaling pathway triggers oxidative stress, inflammation, and apoptosis which later lead to vascular dysfunction induced by diabetes. Polyphenol is a bioactive compound that can be found abundantly in plants such as vegetables, fruits, whole grains, and nuts. This compound exerts therapeutic effects in alleviating diabetes-induced vascular disorder, mainly due to its potential as an anti-oxidative, anti-inflammatory, and anti-apoptotic agent. In this review, we sought to summarize the recent discovery of polyphenol treatments in modulating associated genes involved in the progression of diabetes-induced vascular disorder.

Diabetic Nephropathy (DN) is known as one of the driving sources of End-Stage Renal Disease (ESRD). DN prevalence continues to increase in every corner of the world andthat has been a major concern to healthcare professionals as DN is the key driver of Diabetes Mellitus (DM) morbidity and mortality. Hyperglycaemia is closely connected with the production of Reactive Oxygen Species (ROS) that cause oxidative stress response as well as numerous cellular and molecular modifications. Oxidative stress is a significant causative factor to renal damage, as it can activate other immunological pathways, such as inflammatory, fibrosis, and apoptosis pathways. These pathways can lead to cellular impairment and death as well as cellular senescence. Natural substances containing bioactive compounds, such as polyphenols, have been reported to exert valuable effects on various pathological conditions, including DM. The role of polyphenols in alleviating DN conditions has been documented in many studies. In this review, the potential of polyphenols in ameliorating the progression of DN via modulation of oxidative stress, inflammation, fibrosis, and apoptosis, as well as cellular senescence, has been addressed. This information may be used as the strategies for the management of DN and development as nutraceutical products to overcome DN development., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Clinically, timely reperfusion strategies to re-establish oxygenated blood flow in ischemic heart diseases seem to salvage viable myocardium effectively. Despite the remarkable improvement in cardiac function, reperfusion therapy could paradoxically trigger hypoxic cellular injury and dysfunction. Experimental laboratory models have been developed over the years to explain better the pathophysiology of cardiac ischemia-reperfusion injury, including the in vitro hypoxia-reoxygenation cardiac injury model. Furthermore, the use of nutritional myocardial conditioning techniques have been successful. The cardioprotective potential of flavonoids have been greatly linked to its anti-oxidant, anti-apoptotic and anti-inflammatory properties. While several studies have reviewed the cardioprotective properties of flavonoids, there is a scarce evidence of their function in the hypoxia-reoxygenation injury cell culture model. Hence, the aim of this review was to lay out and summarize our current understanding of flavonoids' function in mitigating hypoxia-reoxygenation cardiac injury based on evidence from the last five years. We also discussed the possible mechanisms of flavonoids in modulating the cardioprotective effects as such information would provide invaluable insight on future therapeutic application of flavonoids.

Long-term nicotine intake is associated with an increased risk of myocardial damage and dysfunction. However, it remains unclear whether targeting mitochondrial reactive oxygen species (ROS) prevents nicotine-induced cardiac remodeling and dysfunction. This study investigated the effects of mitoTEMPO (a mitochondria-targeted antioxidant), and resveratrol (a sirtuin activator) , on nicotine-induced cardiac remodeling and dysfunction. Sprague-Dawley rats were administered 0.6 mg/kg nicotine daily with 0.7 mg/kg mitoTEMPO, 8 mg/kg resveratrol, or vehicle alone for 28 days. At the end of the study, rat hearts were collected to analyze the cardiac structure, mitochondrial ROS level, oxidative stress, and inflammation markers. A subset of rat hearts was perfused ex vivo to determine the cardiac function and myocardial susceptibility to ischemia-reperfusion injury. Nicotine administration significantly augmented mitochondrial ROS level, cardiomyocyte hypertrophy, fibrosis, and inflammation in rat hearts. Nicotine administration also induced left ventricular dysfunction, which was worsened by ischemia-reperfusion in isolated rat hearts. MitoTEMPO and resveratrol both significantly attenuated the adverse cardiac remodeling induced by nicotine, as well as the aggravation of postischemic ventricular dysfunction. Findings from this study show that targeting mitochondrial ROS with mitoTEMPO or resveratrol partially attenuates nicotine-induced cardiac remodeling and dysfunction.

Diabetic cardiomyopathy is one of the major mortality risk factors among diabetic patients worldwide. It has been established that most of the cardiac structural and functional alterations in the diabetic cardiomyopathy condition resulted from the hyperglycemia-induced persistent oxidative stress in the heart, resulting in the maladaptive responses of inflammation and apoptosis. Flavonoids, the most abundant phytochemical in plants, have been reported to exhibit diverse therapeutic potential in medicine and other biological activities. Flavonoids have been widely studied for their effects in protecting the heart against diabetes-induced cardiomyopathy. The potential of flavonoids in alleviating diabetic cardiomyopathy is mainly related with their remedial actions as anti-hyperglycemic, antioxidant, anti-inflammatory, and anti-apoptotic agents. In this review, we summarize the latest findings of flavonoid treatments on diabetic cardiomyopathy as well as elucidating the mechanisms involved.

S-Allylcysteine (SAC) is an extensively studied natural product which has been proven to confer cardioprotection. This potentiates SAC into many clinical relevance possibilities, hence, the use of it ought to be optimally elucidated. To further confirm this, an ischemia/reperfusion model has been used to determine SAC at 10 mM and 50 mM on cardiac function, cardiac marker, and mitochondrial permeability. Using Langendorff setup, 24 adult male Wistar rats' hearts were isolated to be perfused with Kreb-Henseleit buffer throughout the ischemia/reperfusion method. After 20 min of stabilization, global ischemia was induced by turning off the perfusion for 35 min followed by 60 min of reperfusion with either Kreb-Henseleit buffer or SAC with the dose of 10 mM or 50 mM. The cardiac function was assessed and coronary effluent was collected at different timepoints throughout the experiment for lactate dehydrogenase (LDH) measurement. The harvested hearts were then used to measure glutathione while isolated mitochondria for mPTP analysis. SAC-reperfused hearts were shown to prevent the aggravation of cardiac function after I/R induction. It also dose-dependently upregulated glutathione reductase and glutathione level and these were also accompanied by significant reduction of LDH leakage and preserved mitochondrial permeability. Altogether, SAC dose-dependently was able to recover the post-ischemic cardiac function deterioration alongside with improvement of glutathione metabolism and mitochondrial preservation. These findings highly suggest that SAC when sufficiently supplied to the heart would be able to prevent the deleterious complications after the ischemic insult., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This study investigated the impact of prolonged nicotine administration on myocardial susceptibility to ischaemia-reperfusion (I/R) injury in a rat model and determined whether nicotine affects mitochondrial reactive oxygen species (ROS) production and permeability transition in rat hearts. Sprague-Dawley rats were administered 0.6 or 1.2 mg/kg nicotine for 28 days, and their hearts were isolated at end-point for assessment of myocardial susceptibility to I/R injury ex vivo. Rat heart mitochondria were also isolated from a subset of rats for analysis of mitochondrial ROS production and permeability transition. Compared to the vehicle controls, rat hearts isolated from nicotine-administered rats exhibited poorer left ventricular function that worsened over the course of I/R. Coronary flow rate was also severely impaired in the nicotine groups at baseline and this worsened after I/R. Nicotine administration significantly increased mitochondrial ROS production and permeability transition relative to the vehicle controls. Interestingly, pre-incubation of isolated mitochondria with ROS scavengers (superoxide dismutase and mitoTEMPO) significantly abolished nicotine-induced increase in mitochondria permeability transition in isolated rat heart mitochondria. Overall, our data showed that prolonged nicotine administration enhances myocardial susceptibility to I/R injury in rats and this is associated with mitochondrial ROS-driven increase in mitochondrial permeability transition., (© 2020 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

The genus Parkia (Fabaceae, Subfamily, Mimosoideae) comprises about 34 species of mostly evergreen trees widely distributed across neotropics, Asia, and Africa. This review aims to provide an overview of the current status of the species from the genus Parkia in terms of its relationship between its phytochemistry and medical uses. Comprehensive information on Parkia species was retrieved from electronic databases, which were Web of Science, ScienceDirect, PubMed, and Google Scholar. This review identified nine species from genus Parkia with properties of medicinal use. They are used traditionally to treat several ailments, such as diabetes, diarrhea, wounds, hypertension, cough, chronic piles, conjunctivitis, and measles. The most common species studied are P. biglobosa , P. speciosa , P. javanica , P. bicolor , P. biglandulosa , P. filicoidea , and P. clappertoniana . A considerable number of secondary metabolites, such as terpenoids, phenolic acids, flavonoids (aglycone and glycosides), and numerous volatile compounds have been identified in this genus, which are responsible for their diverse pharmacological activities. Their extracts, pure compounds and seed lectins have been reported for their anticancer, antimicrobial, antihypertensive, antiulcer, antidiabetic, anti-inflammatory, antioxidant, antimalarial, hepatoprotective, and antidiarrheal activities. The information gathered in this review might be of help for future studies in terms of the current knowledge on the link between the phytochemical components and medicinal uses. This could facilitate more discoveries on its potentials particularly in the pharmacological characteristics and potential to be developed into modern medicines.

Background: Myocardial infarction (MI) reperfusion therapy causes paradoxical cardiac complications. Following restoration of blood flow to infarcted regions, a multitude of inflammatory cells are recruited to the site of injury for tissue repair. Continual progression of cardiac inflammatory responses does, however, lead to adverse cardiac remodeling, inevitably causing heart failure., Main Body: Increasing evidence of the cardioprotective effects of both invasive and non-invasive vagal nerve stimulation (VNS) suggests that these may be feasible methods to treat myocardial ischemia/reperfusion injury via anti-inflammatory regulation. The mechanisms through which auricular VNS controls inflammation are yet to be explored. In this review, we discuss the potential of autonomic nervous system modulation, particularly via the parasympathetic branch, in ameliorating MI. Novel insights are provided about the activation of the cholinergic anti-inflammatory pathway on cardiac macrophages. Acetylcholine binding to the α7 nicotinic acetylcholine receptor (α7nAChR) expressed on macrophages polarizes the pro-inflammatory into anti-inflammatory subtypes. Activation of the α7nAChR stimulates the signal transducer and activator of transcription 3 (STAT3) signaling pathway. This inhibits the secretion of pro-inflammatory cytokines, limiting ischemic injury in the myocardium and initiating efficient reparative mechanisms. We highlight recent developments in the controversial auricular vagal neuro-circuitry and how they may relate to activation of the cholinergic anti-inflammatory pathway., Conclusion: Emerging published data suggest that auricular VNS is an inexpensive healthcare modality, mediating the dynamic balance between pro- and anti-inflammatory responses in cardiac macrophages and ameliorating cardiac ischemia/reperfusion injury., (Copyright © 2020 Chung, Bretherton, Zainalabidin, Deuchars, Deuchars and Mahadi.)

As the powerhouse of the cells, mitochondria play a very important role in ensuring that cells continue to function. Mitochondrial dysfunction is one of the main factors contributing to the development of cardiomyopathy in diabetes mellitus. In early development of diabetic cardiomyopathy (DCM), patients present with myocardial fibrosis, dysfunctional remodeling and diastolic dysfunction, which later develop into systolic dysfunction and eventually heart failure. Cardiac mitochondrial dysfunction has been implicated in the development and progression of DCM. Thus, it is important to develop novel therapeutics in order to prevent the progression of DCM, especially by targeting mitochondrial dysfunction. To date, a number of studies have reported the potential of phenolic acids in exerting the cardioprotective effect by combating mitochondrial dysfunction, implicating its potential to be adopted in DCM therapies. Therefore, the aim of this review is to provide a concise overview of mitochondrial dysfunction in the development of DCM and the potential role of phenolic acids in combating cardiac mitochondrial dysfunction. Such information can be used for future development of phenolic acids as means of treating DCM by alleviating the cardiac mitochondrial dysfunction.

In spite of medical advances, cardiovascular disease remains a significant concern, imposing a great burden upon the economy and public health of nations by causing the highest morbidity and mortality cases globally. Moreover, it is well established that inflammation is closely linked to the pathogenesis of cardiovascular diseases. Hence, targeting inflammation seems to be a promising strategy in reducing cardiovascular risks. Currently, the importance of natural products in modern medicine is well recognised and continues to be of interest to the pharmaceutical industry. Phenolic acids are a class of phytochemical compounds that are well-known for their health benefits. They consists of various phytochemical constituents and have been widely studied in various disease models. Research involving both animals and humans has proven that phenolic acids possess cardioprotective properties such as anti-hypertensive, anti-hyperlipidemia, anti-fibrotic and anti-hypertrophy activity. Furthermore, numerous studies have proven that phenolic acids in phytochemical constituents such as gallic acid, caffeic acid and chlorogenic acid are promising anti-inflammatory agents. Hence, in this review, we outline and review recent evidence on the role of phenolic acids and their anti-inflammatory significance in studies published during the last 5 years. We also discuss their possible mechanisms of action in modulating inflammation related to cardiovascular disease., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (© 2020 Ali et al. Published by IMR press.)

Increased exposure to nicotine contributes to the development of cardiac dysfunction by promoting oxidative stress, fibrosis, and inflammation. These deleterious events altogether render cardiac myocytes more susceptible to acute cardiac insults such as ischemia-reperfusion (I/R) injury. This study sought to elucidate the role of angiotensin II type I (AT1) receptors in cardiac injury resulting from prolonged nicotine administration in a rat model. Male Sprague-Dawley rats were given nicotine (0.6 mg/kg ip) for 28 days to induce cardiac dysfunction, alone or in combination with the AT1 receptor antagonist, irbesartan (10 mg/kg, po). Vehicle-treated rats were used as controls. Rat hearts isolated from each experimental group at study endpoint were examined for changes in function, histology, gene expression, and susceptibility against acute I/R injury determined ex vivo . Rats administered nicotine alone exhibited significantly increased cardiac expression of angiotensin II and angiotensin-converting enzyme (ACE) in addition to elevated systolic blood pressure (SBP) and heart rate. Furthermore, nicotine administration markedly reduced left ventricular (LV) performance with concomitant increases in myocardial oxidative stress, fibrosis, and inflammation. Concomitant treatment with irbesartan attenuated these effects, lowering blood pressure, heart rate, oxidative stress, and expression of fibrotic and inflammatory genes. Importantly, the irbesartan-treated group also manifested reduced susceptibility to I/R injury ex vivo . These findings suggest that AT1 receptors play an important role in nicotine-induced cardiac dysfunction, and pharmacological approaches targeting cardiac AT1 receptors may thus benefit patients with sustained exposure to nicotine., (Copyright © 2019 Ramalingam, Budin, Mohd. Fauzi, Ritchie and Zainalabidin.)

Prolonged exposure to nicotine accelerates onset and progression of renal diseases in habitual cigarette smokers. Exposure to nicotine, either via active or passive smoking is strongly shown to enhance renal oxidative stress and augment kidney failure in various animal models. In this study, we investigated the effects of resveratrol supplementation on nicotine-induced kidney injury and oxidative stress in a rat model. Male Sprague-Dawley rats were given nicotine (0.6 mg/kg, i.p.) alone or in combination with either resveratrol (8 mg/kg, i.p.), or angiotensin II type I receptor blocker, irbesartan (10 mg/kg, p.o.) for 28 days. Upon completion of treatment, kidneys were investigated for changes in structure, kidney injury markers and oxidative stress. Administration of nicotine alone for 28 days resulted in significant renal impairment as shown by marked increase in plasma creatinine, blood urea nitrogen (BUN) and oxidative stress. Co-administration with resveratrol however successfully attenuated these changes, with a concomitant increase in renal antioxidants such as glutathione similar to the conventionally used angiotensin II receptor blocker, irbesartan. These data altogether suggest that targeting renal oxidative stress with resveratrol could alleviate nicotine-induced renal injury. Antioxidants may be clinically important for management of renal function in habitual smokers., Competing Interests: The authors declare no conflict of interest.

Roselle ( Hibiscus sabdariffa Linn) has been traditionally used as folk medicine for hypertension and maintaining cardiovascular health, with therapeutic potential in protecting against numerous cardiovascular diseases. However, it remains unclear whether roselle can be used for management of cardiac hypertrophy seen after myocardial infarction (MI). This study therefore investigated the effects of aqueous roselle extract on cardiac hypertrophy arising from myocardial infarction both in vivo and in vitro . For in vivo study, male Sprague-Dawley rats were divided into control or MI groups (receiving 85 mg/kg isoproterenol s.c. for 2 days) and were given roselle extract (100 mg/kg, p.o daily) for 28 days. Cardiac structure and functional changes were evaluated at study end-point using histology, Langendorff analysis and gene expression analysis. In vitro effects of roselle were also assessed on ANG II-induced cardiomyocytes hypertrophy using H9c2 cells, simulating cardiac hypertrophy evident after MI. Roselle significantly ameliorated MI-induced cardiac systolic and diastolic dysfunction, as seen across improvement in left ventricular developed pressure (LVDP) and its derivative (LVdP/dt max ) and isovolumic relaxation (Tau). Oxidative stress evident across elevated pro-oxidant markers (NOX2 subunit of NADPH oxidase and 8-isoprostane) as well as reduced antioxidant markers (superoxide dismutase and glutathione) were also significantly attenuated by roselle. Furthermore, roselle treatment markedly reduced markers of cardiac remodeling (cardiac hypertrophy and fibrosis) compared to the untreated MI rats. On in vitro analysis, roselle significantly attenuated ANG II-induced cardiomyoycte hypertrophy in dose-dependent manner. This study demonstrated that roselle attenuates cardiac hypertrophy and dysfunction seen after MI both in vivo and in vitro , and these effects are likely mediated by phenolic compounds found in roselle extract., (Copyright © 2019 Si et al.)

Heart failure-associated morbidity and mortality is largely attributable to extensive and unregulated cardiac remodelling. Roselle (Hibiscus sabdariffa) calyces are enriched with natural polyphenols known for antioxidant and anti-hypertensive effects, yet its effects on early cardiac remodelling in post myocardial infarction (MI) setting are still unclear. Thus, the aim of this study was to investigate the actions of roselle extract on cardiac remodelling in rat model of MI. Male Wistar rats (200-300 g) were randomly allotted into three groups: Control, MI, and MI + Roselle. MI was induced with isoprenaline (ISO) (85 mg/kg, s.c) for two consecutive days followed by roselle treatment (100 mg/kg, orally) for 7 days. Isoprenaline administration showed changes in heart weight to body weight (HW/BW) ratio. MI was especially evident by the elevated cardiac injury marker, troponin-T, and histological observation. Upregulation of plasma levels and cardiac gene expression levels of inflammatory cytokines such as interleukin (IL)-6 and IL-10 was seen in MI rats. A relatively high percentage of fibrosis was observed in rat heart tissues with over-expression of collagen (Col)-1 and Col-3 genes following isoprenaline-induced MI. On top of that, cardiomyocyte areas were larger in heart tissues of MI rats with upregulation of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) gene expression, indicating cardiac hypertrophy. Interestingly, roselle supplementation attenuated elevation of plasma troponin-T, IL-6, IL10, and gene expression level of IL-10. Furthermore, reduction of cardiac fibrosis and hypertrophy were observed. In conclusion, roselle treatment was able to limit early cardiac remodelling in MI rat model by alleviating inflammation, fibrosis, and hypertrophy; hence, the potential application of roselle in early adjunctive treatment to prevent heart failure.

Diabetes mellitus is often associated with cardiac functional and structural alteration, an initial event leading to cardiovascular complications. Roselle (Hibiscus sabdariffa) has been widely proven as an antioxidant and recently has incited research interest for its potential in treating cardiovascular disease. Therefore, this study aimed to determine the cardioprotective effects of H. sabdariffa (roselle) polyphenol-rich extract (HPE) in type-1-induced diabetic rats. Twenty-four male Sprague-Dawley rats were randomized into 4 groups (n = 6/group): nondiabetic, diabetic alone (DM), diabetic supplemented with HPE (DM+HPE), and diabetic supplemented with metformin. Type-1 diabetes was induced with streptozotocin (55 mg/kg intraperitoneally). Rats were forced-fed with HPE (100 mg/kg) and metformin (150 mg/kg) daily for 8 weeks. Results showed that HPE supplementation improved hyperglycemia and dyslipidemia significantly (p < 0.05) in the DM+HPE compared with the DM group. HPE supplementation attenuated cardiac oxidative damage in the DM group, indicated by low malondialdehyde and advanced oxidation protein product. As for the antioxidant status, HPE significantly (p < 0.05) increased glutathione level, as well as catalase and superoxide dismutase 1 and 2 activities. These findings correlate with cardiac function, whereby left ventricle developed pressure in DM+HPE (79.13 ± 3.08 mm Hg) was higher significantly compared with DM (45.84 ± 1.65 mm Hg). Coronary flow of DM+HPE (17.43 ± 0.62 mL/min) was also greater compared with DM (13.02 ± 0.6 mL/min), showing that HPE supplementation improved cardiac contractility and relaxation rate significantly (p < 0.05). Histological analysis showed a marked decrease in cardiomyocyte hypertrophy and fibrosis in DM+HPE compared with the DM group. Ultrastructural changes and impairment of mitochondria induced by diabetes were minimized by HPE supplementation. Collectively, these findings suggest that HPE is a potential cardioprotective agent in a diabetic setting through its hypoglycemic, anti-hyperlipidemia, and antioxidant properties.

Aims: Obesity increase the risks of hypertension and myocardial infarction (MI) mediated by oxidative stress. This study was undertaken to investigate the actions of roselle aqueous extract (R) on cardiotoxicity in obese (OB) rats and thereon OB rats subjected to MI., Main Methods: Male Sprague-Dawley rats were fed with either normal diet or high-fat diet for 8weeks. Firstly, OB rats were divided into (1) OB and (2) OB+R (100mg/kg, p.o, 28days). Then, OB rats were subjected to MI (ISO, 85mg/kg, s.c, 2days) and divided into three groups: (1) OB+MI, (2) OB+MI+R and (3) OB+MI+enalapril for another 4weeks., Key Findings: Roselle ameliorated OB and OB+MI's cardiac systolic dysfunction and reduced cardiac hypertrophy and fibrosis. The increased oxidative markers and decreased antioxidant enzymes in OB and OB+MI groups were all attenuated by roselle., Significance: These observations indicate the protective effect of roselle on cardiac dysfunction in OB and OB+MI rats, which suggest its potential to be developed as a nutraceutical product for obese and obese patients with MI in the future., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Nicotine is a major toxic and hazardous component of cigarette smoke, and it has been widely used in nicotine replacement therapy (NRT). This study was aimed to investigate the effects of chronic low-dose nicotine on sperm characteristics and reproductive organ integrity in adolescent male Sprague-Dawley rats., Methods: Twelve rats were equally divided into two groups. Group I received normal saline, and group II received 0.6 mg/kg body weight nicotine intraperitoneally for 28 consecutive days. At the end of the experimental period, sperm was collected for sperm characteristic evaluation, and the testes and prostate were isolated for biochemical and morphological analysis. The effects of nicotine on the body and reproductive organ weights of the animals were evaluated., Results: Chronic nicotine treatment significantly ( P < 0.05) altered the sperm count, motility, viability, and morphology, and remarkably increased the malondialdehyde ( P < 0.001) and advanced oxidation protein product ( P < 0.05) levels in the testes and prostate of nicotine-treated group compared to control group. Moreover, nicotine caused a significant decrease ( P < 0.05) in the superoxide dismutase activity of the testes. No significant differences were observed in the reduced glutathione level in both of the testes and prostate of nicotine group compared with control group. Nicotine also induced histopathological alteration in the testes., Conclusion: A low-dose nicotine exposure at 0.6 mg/kg caused detrimental effects on sperm characteristics and induced oxidative stress in the testes and prostate.

Vascular endothelial dysfunction (VED) plays an important role in the initiation of cardiovascular diseases. Roselle, enriched with antioxidants, demonstrates high potential in alleviating hypertension. This study was undertaken to investigate the effects of roselle supplementation of VED and remodelling in a rodent model with prolonged nicotine administration. Male Sprague-Dawley rats (n = 6 per group) were administered with 0.6 mg/kg nicotine for 28 days to induce VED. The rats were given either aqueous roselle (100 mg/kg) or normal saline orally 30 min prior to nicotine injection daily. One additional group of rats served as control. Thoracic aorta was isolated from rats to measure vascular reactivity, vascular remodelling and oxidative stress. Roselle significantly lowered aortic sensitivity to phenylephrine-induced vasoconstriction (Endo-(+) C max = 234.5 ± 3.9%, Endo-(-) C max = 247.6 ± 5.2%) compared with untreated nicotine group (Endo-(+) C max = 264.5 ± 6.9%, Endo-(-) C max = 276.5 ± 6.8%). Roselle also improved aortic response to endothelium-dependent vasodilator, acetylcholine (Endo-(+) R max = 73.2 ± 2.1%, Endo-(-) R max = 26.2 ± 0.8%) compared to nicotine group (Endo-(+) R max = 57.8 ± 1.7%, Endo-(-) R max = 20.9 ± 0.8%). In addition, roselle prevented an increase in intimal media thickness and elastic lamellae proliferation to preserve vascular architecture. Moreover, we also observed a significantly lowered degree of oxidative stress in parallel with increased antioxidant enzymes in aortic tissues of the roselle-treated group. This study demonstrated that roselle prevents VED and remodelling, and as such it has high nutraceutical value as supplement to prevent cardiovascular diseases.

Roselle (Hibiscus sabdariffa Linn.) calyces have demonstrated propitious cardioprotective effects in animal and clinical studies; however, little is known about its action on cardiac mechanical function. This study was undertaken to investigate direct action of roselle polyphenols (RP) on cardiac function in Langendorff-perfused rat hearts. We utilized RP extract which consists of 12 flavonoids and seven phenolic acids (as shown by HPLC profiling) and has a safe concentration range between 125 and 500 μg/ml in this study. Direct perfusion of RP in concentration-dependent manner lowered systolic function of the heart as shown by lowered LVDP and dP/dt max , suggesting a negative inotropic effect. RP also reduced heart rate (negative chronotropic action) while simultaneously increasing maximal velocity of relaxation (positive lusitropic action). Conversely, RP perfusion increased coronary pressure, an indicator for improvement in coronary blood flow. Inotropic responses elicited by pharmacological agonists for L-type Ca 2+ channel [(±)-Bay K 8644], ryanodine receptor (4-chloro-m-cresol), β-adrenergic receptor (isoproterenol) and SERCA blocker (thapsigargin) were all abolished by RP. In conclusion, RP elicits negative inotropic, negative chronotropic and positive lusitropic responses by possibly modulating calcium entry, release and reuptake in the heart. Our findings have shown the potential use of RP as a therapeutic agent to treat conditions like arrhythmia.

Hypertension can be caused by various factors while the predominant causes include increase in body fluid volume and resistance in the circulatory system that elevate the blood pressure. Consumption of probiotics has been proven to attenuate hypertension; however, the effect is much strain-dependent. In this study, a newly isolated Lactobacillus casei ( Lb. casei ) strain C1 was investigated for its antihypertensive properties in spontaneously hypertensive rats (SHR). Lactic acid bacteria (LAB) suspension of 11 log colony-forming unit (CFU) was given to SHR (SHR+LAB, n=8), and phosphate buffer saline (PBS) was given as a control in SHR (SHR, n=8) and in Wistar rats as sham (WIS, n=8). The treatment was given via oral gavage for 8 weeks. The results showed that the weekly systolic blood pressure (SBP), mean arterial pressure (MAP), diastolic blood pressure (DBP) and aortic reactivity function were remarkably improved after 8 weeks of bacterial administration in SHR+LAB. These effects were mostly attributed by restoration of wall tension and tensile stress following the bacterial treatment. Although not statistically significant, the level of malondialdehye (MDA) in SHR+LAB serum was found declining. Increased levels of glutathione (GSH) and nitric oxide (NO) in SHR+LAB serum suggested that the bacterium exerted vascular protection through antioxidative functions and relatively high NO level that induced vasodilation. Collectively, Lb. casei strain C1 is a promising alternative for hypertension improvement., Competing Interests: The authors declare no conflicts of interest.

Resistance arteries have been implicated as a major contributing factor in the sequela of disease conditions such as hypertension and diabetes and, as such, are a major focus of cardiovascular research. The paracrine influence of the intimal endothelial layer of resistance arteries is well established. Considering the growing body of evidence substantiating a functionally relevant vascular adventitia, in this study we have established a technique that permits determination of the functional influence of the adventitial layer on resistance artery tone. Isolating adventitial-dependent function, analogous to isolating endothelial function, has potentially significant implications for studying the as yet unexplored role of the microvascular adventitial layer in modulating acute vascular contractile function., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Vascular remodelling is an adaptive mechanism, which counteracts pressure changes in blood circulation. Nicotine content in cigarette increases the risk of hypertension. The exact relationship between nicotine and vascular remodelling still remain unknown. Current study was aimed to determine the effect of clinically relevant dosage of nicotine (equivalent to light smoker) on aortic reactivity, oxidative stress markers and histomorphological changes. Twelve age-matched male Sprague-Dawley rats were randomly divided into two groups, i.e.: normal saline as control or 0.6 mg/kg nicotine for 28 days (i.p., n=6 per group). On day-29, the rats were sacrificed and the thoracic aorta was dissected immediately for further studies. Mean arterial pressure (MAP) and pulse pressure (PP) of nicotine-treated vs. control were significantly increased (p<0.05). Nicotine-treated group showed significant (p<0.05) increase tunica media thickness, and decrease in lumen diameter, suggesting vascular remodelling which lead to prior hypertension state. The phenylephrine (PE)-induced contractile response in nicotine group was significantly higher than control group (ED50=1.44×10(5) M vs. 4.9×10(6) M) (p<0.05~0.001). However, nicotine-treated rat showed significantly lower endothelium-dependent relaxation response to acetylcholine (ACh) than in control group (ED50=6.17×10(7) M vs. 2.82×10(7) M) (p<0.05), indicating loss of primary vascular function. Malondialdehyde (MDA), a lipid peroxidation marker was significantly higher in nicotine group. Superoxide dismutase (SOD) enzymatic activity and glutathione (GSH) were all reduced in nicotine group (p<0.05) vs. control, suggesting nicotine induces oxidative imbalance. In short, chronic nicotine administration impaired aortic reactivity, probably via redox imbalance and vascular remodelling mechanism.

The aim of this study was to evaluate the effects of aqueous extract of roselle on the membrane composition of red blood cells. A total of 32 male Sprague-Dawley rats (230-250 g) were divided randomly into four groups. Diabetic rats were induced streptozotocin (45 mg kg(-1), i.v). The normal and diabetes groups were administrated with distilled water. The other normal and diabetes group were administrated with roselle aqueous extracts (100 mg kg(-1)). After 28 days, the blood was drawn by sinus orbital for biochemical tests including membrane total protein, cholesterol and phosphatidylcholine and morphology of red blood cells was carried out through light microscope. In diabetic rats, the result showed the weight of rat, membrane total protein and Phosphatidylcholine (PCh) were significantly lower (p<0.05), while blood glucose and membrane cholesterol showed significantly higher (p<0.05) than control rats. In diabetic rats demonstrated with roselle, the result showed no significant difference (p>0.05) in weight and blood glucose compared to diabetic rats. The membrane total protein and PCh were significantly higher (p<0.05) than diabetic rats, whereas membrane cholesterol was significantly lower (p<0.05) compared to diabetic rats. The observation red blood cells morphology that showed echinocytes, schistocytes and Heinz body in diabetic rats was caused by oxidative stress damage. The morphology of red blood cells in diabetic rats supplemented with roselle is normal. Aqueous extract of roselle showed potential protective effects on membrane composition of damaged red blood cells.

Objectives: The aim of this study was to investigate the protective effects of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell (RBC) membrane oxidative stress in rats with streptozotocin-induced diabetes., Methods: Forty male Sprague-Dawley rats weighing 230-250 g were randomly divided into four groups (n = 10 rats each): control group (N), roselle-treated control group, diabetic group, and roselle-treated diabetic group. Roselle was administered by force-feeding with aqueous extracts of roselle (100 mg/kg body weight) for 28 days., Results: The results demonstrated that the malondialdehyde levels of the red blood cell membranes in the diabetic group were significantly higher than the levels in the roselle-treated control and roselle-treated diabetic groups. The protein carbonyl level was significantly higher in the roselle-treated diabetic group than in the roselle-treated control group but lower than that in the diabetic group. A significant increase in the red blood cell membrane superoxide dismutase enzyme was found in roselle-treated diabetic rats compared with roselle-treated control rats and diabetic rats. The total protein level of the red blood cell membrane, osmotic fragility, and red blood cell morphology were maintained., Conclusion: The present study demonstrates that aqueous extracts of roselle possess a protective effect against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes. These data suggest that roselle can be used as a natural antioxidative supplement in the prevention of oxidative damage in diabetic patients.