Naringin: Cardioprotective properties and safety profile in diabetes treatment.

Flavonoids derived from plants offer a broad spectrum of therapeutic potential for addressing metabolic syndrome, particularly diabetes mellitus (DM), a prevalent non-communicable disease. Hyperglycemia in DM is a known risk factor for cardiovascular diseases (CVDs), which substantially impact global mortality rates. This review examines the potential effects of naringin, a citrus flavonoid, on both DM and its associated cardiovascular complications, including conditions like diabetic cardiomyopathy. The safety profile of naringin is summarized based on various pre-clinical studies. The data for this review was gathered from diverse electronic databases, including Medline, PubMed, ScienceDirect, SpringerLink, Google Scholar, and Emerald Insight. Multiple pre-clinical studies have demonstrated that naringin exerts hypoglycemic and cardioprotective effects by targeting various vascular mechanisms. Specifically, research indicates that naringin down-regulates the renin-angiotensin and oxidative stress systems while concurrently upregulating ß-cell and immune system functions. Clinical trial outcomes also support the therapeutic potential of naringin in managing hyperglycemic states and associated cardiovascular issues. Moreover, toxicity studies have confirmed the safety of naringin in animal models, suggesting its potential for safe administration in humans. In conclusion, naringin emerges as a promising natural candidate for both antidiabetic and cardioprotective purposes, offering potential improvements in health outcomes. While naringin presents a new avenue for therapies targeting DM and CVDs, additional controlled and long-term clinical trials are necessary to validate its efficacy and safety for human use.

Carveol mitigates the development of the morphine anti-nociceptive tolerance, physical dependence, and conditioned place preference in mice.

Emergence of analgesic tolerance and dependence to morphine is frequently the limiting factor in the use of this agent in the management of pain. Hence, this study aimed to investigate the beneficial effects of the natural compound carveol (CV) against morphine antinociceptive tolerance, dependence and conditioned place preference (CPP) in mice. Behavioural paradigms included hot plate and tail-flick (for tolerance), observation of withdrawal signs (for dependence) while biochemical tests involved the assays for mRNA expression, nitrite levels, antioxidants, and immunohistochemistry studies. Behavioural tests indicated that treatment with CV significantly attenuated the morphine analgesic tolerance, physical dependence and CPP in mice. It was observed during biochemical analysis that CV-treated animals exhibited reduced mRNA expression of inducible nitric oxide synthase (iNOS) and NR2B (an NMDA subtype). In addition, decreased levels of nitrite were observed in mouse hippocampus following CV treatment than morphine administration only. Further, CV enhanced the neuronal innate antioxidants including Glutathione-S-Transferase (GST), glutathione (GSH) and catalase (CAT), while curtailed lipid peroxidase (LPO) levels in mice brain tissues. Moreover, CV exerted significant anti-inflammatory effects as evidenced by reduced expression of TNF-α and p-NF-κB in these animals than with morphine treatment only. Together, anti-inflammatory and antioxidant effects might confer needed neuro-protection following morphine administration. These observations warrant further investigations of the beneficial role of CV as a novel agent in overcoming the development of tolerance and physical dependence following morphine use.

Evaluation of the Cardiovascular Effects of Coriandrum sativum and Citrus limon to Treat Arsenic-Induced Endothelial Damage and Hypertension in Rats.

Based on the vernacular reputation of Coriandrum sativum and Citrus limon to treat hypertension, this study was designed to explore the cardiovascular effects of C. sativum (CS) and C. limon (CL) on arsenic-induced hypertension and endothelial damage. Hypertension was induced by arsenic (100 ppm) in drinking water. The crude methanolic extracts of CS and CL were tested for in vivo and in vitro activities using Power Lab. High performance liquid chromatography analysis of CS and CL showed the presence of phenolic compounds. In anesthetized rats, CS (50 mg) and CL (10 mg) showed a marked decrease in blood pressure of 51% and 35%, respectively. Similarly, ascorbic acid (10 mg) also showed a decreased blood pressure (41%). The CS and CL caused complete relaxation (0.003−5 mg/mL) against phenylephrine (1µM) and high K+ (80 mM)-induced contraction. The CS and CL, independently and in combination, exhibited marked (p < 0.001) attenuation in the blood pressure of the arsenic-induced hypertensive rats when compared with the controls. The beneficial effects of the CS and CL were also observed on lipid peroxidation and eNOS. These data suggest that CS and CL possess significant antihypertensive activity, possibly mediated via endothelium protection, and anti-oxidant effects. Thus, this study provides a rationale for the medicinal use of CS and CL in hypertension and also against arsenic-induced cardiovascular complications.

Ajuga bracteosa Exerts Antihypertensive Activity in l-NAME-Induced Hypertension Possibly through Modulation of Oxidative Stress, Proinflammatory Cytokines, and the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway.

Ajuga bracteosa has been used in traditional medicine to treat hypertension and other ailments. The present study has been designed to investigate the beneficial effects of A. bracteosa in l-nitro arginine methyl ester (l-NAME)-induced hypertensive rats. Hypertension was induced by intraperitoneal injection of l-NAME (185 µmol kg-1 i.p.). The aqueous methanol extract of A. bracteosa (AMEAB, 250 and 500 mg kg-1) and coumarin (30 and 70 mg kg-1) were administered orally from day 8 to day 35 of the study. In vivo antihypertensive activity was assessed by measuring the blood pressure using a PowerLab data system. The effects of the AMEAB and coumarin on nitric oxide (NO), cyclic guanosine monophosphate (cGMP), interleukin-6 (IL-6), the tumor necrosis factor (TNF-α), and oxidative stress markers were also assessed using kit methods. Phytochemical profiling of the AMEAB was carried out through high-performance liquid chromatography (HPLC) where quercetin, gallic acid, caffeic acid, vanillic acid, benzoic acid, syringic acid, p-coumaric acid, and ferulic acid were labeled as plant constituents including coumarin. The AMEAB and coumarin significantly reduced blood pressure at the tested doses of 500 and 70 mg kg-1, respectively. Serum levels of NO and cGMP were found to be significantly increased in AMEAB- and coumarin-treated groups when compared with only l-NAME-challenged rats. In addition, a marked decrease was noticed in the serum concentrations of proinflammatory cytokines (IL-6 and TNF-α) in AMEAB- and coumarin-treated rats. Moreover, in AMEAB- and coumarin-treated animals, a noticeable improvement was observed in the levels of antioxidant enzymes including catalase, superoxide dismutase, and malonaldehyde, and the total oxidant status when compared with those of only l-NAME-challenged rats. The data of real-time polymerase chain reaction (RT-PCR) experiments supported that the antihypertensive and anti-inflammatory activities of the AMEAB and coumarin are possibly mediated through modulation of endothelial nitric oxide synthase (eNOS), angiotensin-converting enzyme (ACE), nuclear factor (NF)-kB, and COX-2 gene expressions. This study concludes that A. bracteosa possesses an antihypertensive effect mediated through the modulation of the antioxidant, anti-inflammatory, and NO/cGMP pathways, thus providing a rationale to the antihypertensive use of A. bracteosa in traditional medicine.

Ziziphus Oxyphylla hydro-methanolic extract ameliorates hypertension in L-NAME induced hypertensive rats through NO/cGMP pathway and suppression of oxidative stress related inflammatory biomarkers.

ETHNOPHARMACOLOGICAL RELEVANCE: Ziziphus Oxyphylla belongs to family Ziziphus and has been used traditionally in hypertension. It is enriched with quercetin and kaempferol derivatives, catechin and cyclopeptide alkaloids. AIM: The current research evaluates the antihypertensive potential of aqueous methanolic extract of Z. oxyphylla (AMEZO) in NG-nitro-L-arginine methyl ester (LNAME) induced hypertension in rats. MATERIAL AND METHODOLOGY: Phytochemical analysis of AMEZO was carried out using high performance liquid chromatography (HPLC) and electrospray ionization mass spectrometry (ESI-MS/MS). Antihypertensive activities of AMEZO (200 and 400 mg/kg) and Kaempferol were assessed in L-NAME (185 µmol/kg, intraperitoneal) injected hypertensive rats. In normotensive rats, blood pressure was assessed using Power Lab data system. Serum and tissue samples were preserved for estimation of nitric oxide (NO), Cyclic guanosine monophosphate (cGMP), interleukin-6 (IL-6), tumor necrosis factor (TNF- α) and oxidative stress markers respectively. mRNA levels of eNOS, ACE, COX-2 and NF-kB genes were assessed through qPCR. RESULTS: The HPLC and ESI-MS/MS identified kaempferol, quercetin, catechin, ceanothic acid, zizybernalic acid and oxyphylline F. Chronic administration of AMEZO and kaempferol in L-NAME induced hypertensive rats significantly (p < 0.001) reduced systolic, diastolic and mean blood pressure. AMEZO and kaempferol caused meaningfully improved (p < 0.001) serum NO and cGMP levels. AMEZO administration also noticeably decrease the elevated IL-6 and TNF- α concentration in hypertensive animals. Administration of AMEZO and kaempferol also improved oxidative stress markers (MDA, CAT, SOD, GSH). The antihypertensive activity of AMEZO also resulted in upregulation of eNOS and downregulation of ACE. CONCLUSION: These data depict that AMEZO and kaempferol showed antihypertensive activity in LNAME induced hypertensive rats possibly mediated through improvement in NO and cGMP levels, modulation of mRNA expression of eNOS, ACE, COX-2 and NF-kB and suppression of oxidative stress related inflammatory markers, proposing a defensive role in cardiovascular diseases.

Hydroethanolic Extract of A. officinarum Hance Ameliorates Hypertension and Causes Diuresis in Obesogenic Feed-Fed Rat Model.

Alpinia officinarum Hance (Zingiberaceae) has been used widely in traditional Chinese and Ayurvedic medicines. Its folkloric uses include relieving stomach ache, treating cold, improving the circulatory system, and reducing swelling. Its effectiveness and mechanism of antihypertension in obesity-induced hypertensive rats have not been studied yet as per our knowledge. This study has been designed to provide evidence of underlying mechanisms to the medicinal use of A. officinarum as a cardiotonic using an obesity-induced hypertension model in rats. Chronic administration of A. officinarum caused a marked reduction in the body weight gain and Lee index of rats compared to the obesogenic diet-fed rats. Its administration also caused attenuation in blood pressure (systolic, diastolic, and mean), serum total cholesterol, triglyceride, and leptin, while an increase in serum HDL and adiponectin levels was noticed. The catalase and superoxide dismutase enzymatic activities were found to be remarkable in the serum of A. officinarum-treated animal groups. A. officinarum showed mild to moderate diuretic, hepatoprotective, and reno-protective effects. The A. officinarum-treated group showed less mRNA expression of 3-hydroxy-3-methylglutaryl-CoA reductase while the mRNA expression of peroxisome proliferator-activated receptor and mRNA expression of cholesterol 7 alpha-hydroxylase were raised in comparison to the hypertensive group of rats evaluated by quantitative real-time polymerase chain reaction. These findings show that A. officinarum possesses antihypertensive and diuretic activities, thus providing a rationale to the medicinal use of A. officinarum in cardiovascular ailments.