@article {52, title = {Vitamin D3, L-Arginine, L-Citrulline, and Antioxidant Supplementation Enhances Nitric Oxide Bioavailability and Reduces Oxidative Stress in the Vascular Endothelium {\textendash} Clinical Implications for Cardiovascular System}, journal = {Pharmacognosy Research}, volume = {12}, year = {2020}, month = {February 2020}, pages = {17-23}, type = {Original Article}, chapter = {17}, abstract = {

Background: Nitric oxide (NO) is a crucial signaling molecule which regulates the blood flow and prevents the adhesion of blood components to the vascular wall. A deficiency in bioavailable NO concentration is associated with the dysfunction of endothelial NO synthase (eNOS) and/or an increase in oxidative stress. The deficiency of bioavailable NO is a common denominator of several cardiovascular diseases, including diabetes, atherosclerosis, and hypertension. Materials and Methods: We used a nanomedical technology to elucidate the balance between bioavailable NO and oxidative stress (peroxynitrite ONOO-) in human umbilical vein endothelial cells (HUVECs) treated with a supplement containing L-arginine, L-citrulline, Vitamin D3, and antioxidants. Nanosensors, with a diameter of 200{\textendash}300 nm, are capable of measuring in situ NO and peroxynitrite (ONOO-) concentrations produced by single endothelial cells. Results: The ratio of the concentration of cytoprotective NO [NO] to the concentration of cytotoxic peroxynitrite [ONOO-] was used to estimate the efficiency of eNOS. HUVECs incubated with L-citrulline, L-arginine, and Vitamin D3 increased the [NO]/[ONOO-] ratio by 25\%, while in the presence of antioxidants, the increase was 15\%. The synergistic effect between the mix of L-arginine, L-citrulline, Vitamin D3, and antioxidants was a favorable increase of the overall [NO]/[ONOO-] ratio by 50\%. Conclusion: The findings of the study presented here clearly indicate that L-arginine, L-citrulline, and Vitamin D3 can significantly alter the function of the endothelium and NO production, in a favorable manner, while pointedly reducing ONOO- {\textendash} the main component of oxidative stress. This effect can be significantly potentiated in the presence of antioxidants.

}, keywords = {Antioxidant, Endothelium, L-arginine, L-citrulline, Nitric oxide, Peroxynitrite, Vitamin D3}, doi = {10.4103/pr.pr_79_19}, author = {Hazem Dawoud and Tadeusz Malinski} } @article {182, title = {Chromatographic Profiles, Anti-inflammatory, and Cytotoxicity Potential of Extracts of Banisteriopsis pubipetala (A. Juss)}, journal = {Pharmacognosy Research}, volume = {11}, year = {2019}, month = {November,2019}, pages = {339-345}, type = {Original Article}, chapter = {339}, abstract = {

Background: Banisteriopsis pubipetala is a little-studied species belonging to the same genus of B. caapi, which stands out for the bioactive compounds known to be important in the degenerative diseases treatment. Objective: The objective is to analyze the anti-inflammatory and cytotoxic potential and chromatographic profile of the extracts of B. pubipetala. Materials and Methods: The investigation of the chromatographic profile was performed through high-performance liquid chromatography diode-array detector. Cell viability was determined by a quantitative colorimetric assay with 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide. In the pharmacological tests, interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), IL-10, and nitric oxide (NO) levels in cell culture supernatants were performed. Results: In the leaf were observed nine major compounds and in the stem five major compounds. The extracts of B. pubipetala demonstrated concentration-dependent behavior regarding cytotoxicity. The fraction in dichloromethane had inhibitory concentration of 50\% (IC50) = 67.39 μg/mL whereas the extract in ethyl acetate had IC50 = 103.37 μg/mL. The results showed that extracts significantly reduced the production of IL-6 and TNF-α by cells 3T3 cells, however increased the production of IL-10 and NO. Conclusion: The results of the tests indicate that the extracts of B. pubipetala evaluated have potential anti-inflammatory properties and may promote the regulation of inflammation levels.

}, keywords = {Banisteriopsis pubipetala, Interleukin-10, Interleukin-6, Malpighiaceae, Nitric oxide, Tumor necrosis factor-alpha.}, doi = {10.4103/pr.pr_71_19}, author = {Jeane Ferreira Leal de Freitas and Fl{\'a}via Dayrell Fran{\c c}a and M{\'\i}riam Martins Chaves and Elytania Veiga Menezes and Afr{\^a}nio Farias de Melo J{\'u}nior and Dario Alves de Oliveira and Clarice Avelar Almeida and Kamylla Santos Teixeira and Murilo Malveira Brand{\~a}o and Vanessa de Andrade Royo} } @article {344, title = {The Effect of Capsicum Oleoresin on Nitric Oxide Production and Nitric Oxide Synthase Gene Expression in Macrophage Cell Line}, journal = {Pharmacognosy Research}, volume = {10}, year = {2018}, month = {October 2018}, pages = {343-346}, type = {Original Article}, chapter = {343}, abstract = {

Background: Nitric oxide (NO) is an inflammatory agent produced by macrophages. It also acts as a neurotransmitter. However, overproduction of NO results in acute or chronic inflammation. Capsicum is well known for its anti-oxidant, anti{\textendash}inflammatory, and anticancer properties. Objective: The objective of this study was to evaluate the effect of capsicum oleoresin on NO production and NO synthase gene expression in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophage cell line. Materials and Methods: Macrophage RAW 264.7 cells were obtained from the National Centre for Cell Science, Pune with Passage no 16. RAW macrophages were treated with 12.5 μg/ml, 25 μg/ml, and 50 μg/ml of Capsicum extract with 1 μg/ml of LPS and incubated for 24 h. Results: When capsicum was added at three different doses of 12.5 μg/ml, 25 μg/ml, and 50 μg/ml, the inducible NO synthase (iNOS) levels was significantly suppressed, compared to that of LPS treatment only. The level of NO increased by LPS induction was significantly decreased in a dose-dependent manner when treated with different concentrations of capsicum extract and capsicum had a suppressing effect on iNOS gene expression in LPS {\textendash} stimulated RAW 264.7 macrophage. Conclusion: This study concludes that capsicum oleoresin is good enough to suppress iNOS gene expression and NO production. Hence, it may be used in inflammatory conditions with excessive NO production.

}, keywords = {Anti-inflammatory, Anti-oxidant, Capsicum oleoresin, Macrophages, Nitric oxide}, doi = {10.4103/pr.pr_46_18}, author = {Srinivasan Manthra Prathoshni and Roy Anitha and Thangavelu Lakshmi} } @article {479, title = {Kolaviron, Biflavonoid Complex from the Seed of Garcinia kola Attenuated Angiotensin II- and Lypopolysaccharide-induced Vascular Smooth Muscle Cell Proliferation and Nitric Oxide Production}, journal = {Pharmacognosy Research}, volume = {8}, year = {2018}, month = {March 2016}, pages = {50-55}, type = {Original Article}, chapter = {50}, abstract = {

Introduction: Kolaviron (KV), a biflavonoid extract from Garcinia kola seeds has been reported to possess anti-inflammatory, anti-oxidant, hepato-protective, cardio-protective, nephro-protective and other arrays of chemopreventive capabilities but the mechanism of action is still not completely understood. Materials and Methods: In this study, we investigated the anti-proliferative, anti-inflammatory and anti-oxidative potential of KV in cultured Vascular Smooth Muscle Cells (VSMCs). Effects of KV (25-100 μg/mL) on VSMC proliferation alone or following treatments with mitogen and proinflammatory agents Angiotensin II (Ag II, 10-6 M) and lipopolysaccharide (LPS, 100 μg/mL) and effects on NO production were determined. Cellular proliferations were determined by MTT assay, nitric oxide (NO) level was determined by Griess assay. KV dose-and time dependently attenuated VSMC growth. Results: Treatment of VSMCs with Ag II and LPS significantly enhanced proliferation of the cell which was significantly attenuated by the treatment with KV. Treatment of VSMC with LPS significantly increased nitric oxide (NO) level in the media which was attenuated by KV. These results demonstrated anti-proliferative antiinflammatory properties of KV as it clearly inhibited cellular proliferation induced by mitogens as well as LPS-induced inflammatory processes. Conclusion: Therefore, KV may mitigate cardiovascular conditions that involve cell proliferation, free radical generation and inflammatory processes such as hypertension, diabetes and stroke. However, the molecular mechanism of action of KV needs to be investigated.

}, keywords = {Angiotensin II, Cardiovascular diseases, cell proliferation, Kolaviron, lipopolysaccharide, Nitric oxide, vascular smooth muscle cells}, doi = {10.4103/0974-8490.178647}, author = {Ademola Adetokunbo Oyagbemi and Temidayo Olutayo Omobowale and Adeolu Alex Adedapo and Momoh Audu Yakubu} } @article {537, title = {Autonomic Receptors and Nitric-Oxide Involvements in Mediating Vasorelaxation Effect Induced by Syzygium polyanthum Leaves Extract}, journal = {Pharmacognosy Research}, volume = {9}, year = {2017}, month = {December 2017}, pages = {s9-s14}, type = {Original Article}, chapter = {s9}, abstract = {

Context: Syzygium polyanthum (Wight) Walp leaves are traditionally used by Malays for treating hypertension. Our previous study showed that aqueous extract of S. polyanthum (AESP) and methanolic extract of S. polyanthum (MESP) extracts of S. polyanthum leaves significantly reduced blood pressure of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Aims: This study aimed to investigate their vasorelaxation potential and the possible involvement of autonomic receptors and nitric oxide in mediating their effect. Settings and Design: Both extracts will be tested on isolated thoracic aorta rings of WKY and SHR. The involvement of autonomic receptors and nitric oxide will be elucidated using respective blockers. Materials and Methods: Isolated thoracic aorta rings from WKY and SHR were mounted onto myograph chambers to measure changes in the aorta tension. Increasing concentrations of AESP and MESP, from 1 {\textmu}g/ ml to 10 mg/ml were added onto the myograph chambers. Blockers such as atropine (1 {\textmu}M), phentolamine (1 {\textmu}M), propranolol (1 {\textmu}M), and Nω-nitro-l-arginine methyl ester (100 {\textmu}M) were preincubated before addition of extracts to check for involvement of muscarinic, α- and β-adrenergic receptors (AR) as well as nitric oxide, respectively. Statistical Analysis Used: Two-way ANOVA, followed by post hoc Bonferroni test was used, where P \< 0.05 (two-tailed) was considered statistically significant. Results: AESP and MESP caused significant vasorelaxations through nitric oxide pathway. The former was mediated through α-AR while the latter was mediated by β-adrenergic and muscarinic receptors. Conclusion: Vasorelaxation effect by AESP and MESP involved nitric oxide pathway which is possibly mediated by the autonomic receptors.

}, keywords = {Antihypertensive, Ethnomedicine, Hypertension, Nitric oxide, Syzygium polyanthum, Vasorelaxation}, doi = {10.4103/pr.pr_69_17}, author = {Azlini Ismail and Wan Amir Nizam Wan Ahmad} } @article {576, title = {Oleanolic Acid Prevents Increase in Blood Pressure and Nephrotoxicity in Nitric Oxide Dependent Type of Hypertension in Rats}, journal = {Pharmacognosy Research}, volume = {7}, year = {2015}, month = {October 2015}, pages = {385-392}, type = {Original Article}, chapter = {385}, abstract = {

Background: Recently, we have reported antihypertensive activity of oleanolic acid (OA) in glucocorticoid-induced hypertension with restoration of nitric oxide (NO) level. However, the involvement of NO-releasing action of OA was unclear. Objective: To explore antihypertensive activity of OA in Nω-nitro-L-arginine methyl ester (L-NAME) hypertensive rats wherein NO is completely blocked, which would allow exploring the possibility of involvement of NO-releasing action of OA. Materials and Methods: Five groups of rats were investigated as normal control, L-NAME (40 mg/kg/day), L-NAME + enalapril (15 mg/kg/day), L-NAME + l-arginine (100 mg/kg/day), and L-NAME + OA (60 mg/kg/day) for 4 weeks. The systolic blood pressure, body weight, and heart rate were measured weekly for 4 weeks. Serum nitrate/nitrite (NOx) level, urine electrolytes concentration, cardiac mass index, and serum creatinine level were determined followed by organ histopathology. Results: OA and enalapril delayed the rise in blood pleasure following L-NAME administration. Decreased serum NOx level was not significantly increased with any of the treatment. OA produced a small, though nonsignificant, increase in the NOx level. L-NAME administration did not affect cardiac mass index. There was an increase in serum creatinine upon L-NAME administration which was prevented by OA. Decreased urine volume, urine sodium and potassium were reversed by OA. Conclusion: These results suggest that the antihypertensive effect of OA in L-NAME hypertension is due to diuresis and nephroprotection. However, OA has nonsignificantly affected the NO levels.

}, keywords = {Endothelial dysfunction, Invasive blood pressure, Nitric oxide, Triterpenoid, Viscum.}, doi = {10.4103/0974-8490.159575} } @article {730, title = {Biphasic effect of Solanum nigrum fruit aqueous extract on vascular mesenteric beds in non-diabetic and streptozotocin-induced diabetic rats}, journal = {Pharmacognosy Research}, volume = {6}, year = {2014}, month = {March,2014}, pages = {148-152}, type = {Original Article}, chapter = {148}, abstract = {

Background: In Asia, Solanum nigrum fruit is traditionally used to manage, control, and treat diabetes. Objective: This study was carried out to investigate the endothelium and nitric oxide roles in Solanum nigrum-induced vasorelaxation in non-diabetic and diabetic rat vessels. Materials and Methods: Diabetes was induced by a single i.p. injection of streptozotocin. Eight weeks later, superior mesenteric arteries of non-diabetic and diabetic groups were isolated and perfused according to the McGregor method. Solanum nigrum fruit extract (SNE) at concentrations of 0.00001 to 0.6 mg/ml was added to the medium and perfusion pressure was recorded. Results: Baseline perfusion pressure of diabetic group was significantly higher than non-diabetic rats in both intact and denuded endothelium. The low concentrations of SNE have vasodilatory effect in the diabetic and non-diabetic, but high concentrations of SNE produce initial significant contractions, followed by secondary relaxations in normal and diabetic rats. We observed vasorelaxation at low and high concentrations of SNE in both diabetic and non-diabetic groups after endothelium denudation. SNE-induced vasorelaxation in diabetic group is mediated by both endothelium and smooth muscle, but the relaxatory effect of SNE in non-diabetic group is not mediated by endothelium, and SNE has direct action on the smooth muscle. Conclusion: Although the part of SNE-induced relaxation in diabetic vessel was mediated by endothelium, nitric oxide didn{\textquoteright}t play any role in this action, and maybe we can use SNE in the management of diabetes vessel complications in future.

}, keywords = {Diabetes mellitus, Mesenteric bed, Nitric oxide, Solanum nigrum fruit extract vasorelaxation}, doi = {10.4103/0974-8490.129036}, author = {Shahla Sohrabipour and Fatemah Kharazmi and Nepton Soltani and Mohammad Kamalinejad} } @article {819, title = {Effects of L-citrulline Diet on Stress-induced Cold Hypersensitivity in Mice}, journal = {Pharmacognosy Research}, volume = {6}, year = {2014}, month = {August,2014}, pages = {297-302}, type = {Original Article}, chapter = {297}, abstract = {

Background: L-citrulline is an amino acid discovered in watermelon (Citrullus lanatus, Cucurbitaceae) and is a known component of the nitric oxide (NO) cycle that plays an important role in adjusting blood circulation and supplying NO and a key component of the endothelium-derived relaxing factor. Objective: The objective of this study is to evaluate the effect of L-citrulline on a newly established stress-induced cold hypersensitivity mouse model. Materials and Methods: When normal mice were forced to swim in water at 25{\textdegree}C for 15 min, their core body temperature dropped to 28.9{\textdegree}C, and then quickly recovered to normal temperature after the mice were transferred to a dry cage at room temperature (25{\textdegree}C). A 1-h immobilization before swimming caused the core body temperature to drop to ca. 24.1{\textdegree}C (4.8{\textdegree}C lower than normal mice), and the speed of core body temperature recovery dropped to 57\% of the normal control. We considered this delay in recovery from hypothermia to be a sign of stress-induced cold hypersensitivity. Similar cold hypersensitivity was induced by administration of 50 mM L-NG-nitroarginine methyl ester, a NO synthesis inhibitor. Results: In this study, we showed that recovery speed from the stress-induced hypothermia remarkably improved in mice fed a 1\% L-citrulline-containing diet for 20 days. Furthermore, the nonfasting blood level of L-arginine and L-citrulline increased significantly in the L-citrulline diet group, and higher serum nitrogen oxide levels were observed during recovery from the cold. Conclusions: These results suggested that oral L-citrulline supplementation strengthens vascular endothelium function and attenuates stress-induced cold hypersensitivity by improving blood circulation.

}, keywords = {Citrullus lanatus, Cold hypersensitivity, Cucurbitaceae, L-citrulline, Nitric oxide}, doi = {10.4103/0974-8490.138269}, author = {Yoshinori Kobayashi and Kazuki Narita and Kotaro Chiba and Hiroaki Takemoto and Masahiko Morita and Koji Morishita} } @article {622, title = {The Effects of Unripe Grape Extract on Systemic Blood Pressure, Nnitric Oxide Production, and Response to Angiotensin II Administration}, journal = {Pharmacognosy Research}, volume = {5}, year = {2013}, month = {April 2013}, pages = { 60-64}, type = {Original Article }, chapter = {60}, abstract = {

Background:\ Hypertension is the most common disease in the world. In Iranian folk medicine, unripe grape juice has been used as antihypertention remedy, but no data is documented for this popular belief. This study was designed to determine the effect of unripe grape extract (UGE) on blood pressure and the response to angiotensin II in rat.\ Materials and Methods:\ Unripe grape was collected, air dried, and extracted and concentrated. Four groups of Wistar rats received single doses of 125, 250, and 500 mg/kg of UGE or saline, respectively. The direct blood pressure and the serum nitrite level were measured one hour post UGE administration. The animals also were subjected to the infusion of various angiotensin II concentrations (100, 300, and 1000 μg/kg/min), and blood pressure was determined.\ Results:\ Mean arterial, systolic, and diastolic pressures (MAP, SP, and DP) in all UGE treated groups were less than the control group, but only at the dose of 125 mg/kg (Group 1) they were significantly different (\ P\ \< 0.05). The level of nitrite in groups 1-3 were significantly greater than the control group (\ P\ \< 0.05). No significant differences were detected for the MAP, SP, and DP to different concentrations of angiotensin II among these groups.\ Conclusion:\ UGE potentially attenuate MAP, SP, and DP via vasodilatation induced by nitric oxide production.

}, keywords = {Angiotensin II, Blood Pressure, Nitric oxide, Unripe Grape Extract, VitisVinifera}, doi = {10.4103/0974-8490.110511}, author = {Mehdi Nematbakhsh and Behzad Zolfaghari and Fatemeh Eshraghi and Tahereh Safari and Zahra Pezeshki and Seyyed Mohammad-Ali Sorooshzadeh} } @article {747, title = {Anti-inflammatory Activity of Ixora coccinea Methanolic Leaf Extract}, journal = {Pharmacognosy Research}, volume = {1}, year = {2009}, month = {January 2010 }, pages = {80-90}, type = {Original Article}, chapter = {80}, abstract = {

The anti-inflammatory activity of methanolic leaf extract (MLE) of Lxora coccinea Linn. (Rubiaceae) was investigated in this study. MLE showed dose-dependent anti-inflammatory activity in carrageenan-induced rat paw edema model (r = 0.7; P\<0.01). MLE at a dose of 500, 1000, and 1500 mg/kg showed maximum inhibition of edema 36.7, 46.5, and 64.5\% respectively (P\<0.01). Oral administration of MLE of rats at a dose of 1500 mg/kg significantly inhibited peritoneal phagocytic cell infiltration (45.9\%; P\<0.05), impaired nitric oxide (NO) production in peritoneal cells (40.8\%; P\<0.01) and showed antihistamine activity (54.9\%; P\<0.01). In vitro treatment of rat peritoneal cells with MLE inhibited NO production dosedependently (82.2\% at 400 μg/ml, r = 0.99; P\<0.05). MLE also possessed significant, dose-dependent in vitro anti-oxidant activity (r = 0.88; P\<0.01; IC50 value = 8.0 μg/ml), membrane stabilizing activity (r = 0.81; P\<0.01; IC50 value = 6.4 ng/ml) and lipid peroxidation activity (36.7\% at 250 μg/ml; P\<0.01). Thirty-day oral treatment of rats with 1500 mg/kg did not show any adverse signs of toxicity or behavioral changes. These results suggest that anti-inflammatory activity of\ L. coccinea is mediated via inhibition NO production, phagocytic cell infiltration, anti-histamine effect, scavenging of free radicals, membrane stabilizing activity and lipid peroxidation.

}, keywords = {anti-inflammatory activity, Cell infiltration, Lxora coccinea, Membrane stabilization, Nitric oxide, nti-oxidant}, doi = {Nil}, author = {S. M. Handunnetti and R. R. Kumara and S. A. Deraniyagala and W. D. Ratnasooriya} } @article {927, title = {Antioxidative Effect of Trichosanthes tricuspidata Root Extract on Sildenafil Induced Migraine in Albino Mice}, journal = {Pharmacognosy Research}, volume = {1}, year = {2009}, month = {January 2010 }, pages = {402-405}, type = {Original Article}, chapter = {402}, abstract = {

Migraine is considered a neurovascular disease involving the dilatation of cerebral arteries. Because of their dual role in modulating neuronal and vascular events, neuropeptides have been implied to be of importance in migraine pathophysiology. It is a highly prevalent disorder which manifests clinically as moderate to severe or severe headache attacks with frequent frontotemporal unilateral location and associated symptoms. The disability of migraine results in considerable economic and social losses .Nitric oxide, a short lived vasodilator and weak oxygen radical has been implicated in the genesis of migraine headaches. Hence the role of all enzymic and non enzymic antioxidants becomes in evitable in the treatment of migraine. Trichosanthes tricuspidata{\textquoteright}s (red apple gourd) antioxidant effect was tested over Sildenafil induced migraine in female albino mice. The levels of antioxidant enzymes such as super oxide dismutase (SOD), lipid peroxidase(LPO), catalase(CAT) and glutahione peroxidase(GPx) were more promising in the treatment group fed with the root extract of Trichosanthes tricuspidata.

}, keywords = {Nitric oxide, Oxygen radical, Sildenafil, Stress}, doi = {Nil}, author = {Nithiya .P and Karthik Mohan} }