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Rosemary plant extract as a natural anti-oxidant is 4 times stronger than synthetic anti-oxidant like BHT and BHA. For this reason, it has been under attention not only for its anti-oxidant properties rather for its anti-inflammatory, anti-tumor, anti-bacterial, and anti-virus properties in different studies. This research investigates the effects of temperature, time, pH, and substance concentration in the labeling of irradiated rosmarinic acid by radioisotope gallium-67 as a high-resolution imaging agent for SPECT imaging. In this study, gamma irradiated rosmarinic acid nanoparticles at 20 kGy and 30 kGy levels in two concentrations of 0.5 and 1% were radiolabeled by gallium-67 radioisotope produced in Karaj cyclotron, and their efficiency and radiochemical purity were compared. Labeling conditions (including pH, temperature, time, and compound concentration) were investigated. Quality control was performed by thin-layer chromatography (RTLC). Resulting from the experiments, 30 kGy level and 1% concentration at 45 °C for 30 minutes at pH = 5.5-6 proved to be the best time for labeling rosemary nanoparticles, and the highest radiochemical purity achieved was 95%; radio conjugate also showed good stability after 12 hours.

Background and Objectives: Nonalcoholic steatohepatitis is a severe liver disease characterized by excess lipid accumulation (steatosis) and inflammation in the liver. Endoplasmic reticulum stress is considered one of the crucial factors in nonalcoholic steatohepatitis pathophysiology. Rosmarinic acid is a herbal medicine with antioxidant and anti-inflammatory properties. This study aimed to evaluate the effect of rosmarinic acid on reducing the endoplasmic reticulum stress induced by nonalcoholic steatohepatitis in male Swiss-type mice. Methods: The study animals were grouped into four: Saline, rosmarinic acid, nonalcoholic steatohepatitis, and nonalcoholic steatohepatitis-rosmarinic acid. Nonalcoholic steatohepatitis was induced by a diet without methionine-choline for 8 weeks, and rosmarinic acid was injected intraperitoneally daily for 8 weeks in mice. After 8 weeks, the animals were killed, and their liver samples were obtained. Real-time PCR was used for molecular studies. Data analyses were performed by one-way analysis of variance and Tukey's post hoc test. Results: Findings of this study showed that rosmarinic acid alleviated mRNA levels of GRP78, IRE-1, and PERK while increasing the Apo B expression. Conclusion: The results suggest that rosmarinic acid ameliorates endoplasmic reticulum stress parameters, upregulates Apo B expression as a key factor in triglyceride exit from the liver, and thereby improves nonalcoholic steatohepatitis in male Swiss-type mice.

Background and Objectives: Nonalcoholic Steatohepatitis (NASH) is one of the common liver diseases, characterized by excessive lipid accumulation (steatosis) and inflammation in the liver. Inflammation is one of main reasons for this disease which takes place from different pathways. Rosmarinic Acid (RA) is an antioxidant and anti-inflammatory product with positive effects on the improvement of liver injuries. This study aims to evaluate protective effect of RA against liver inflammation caused by NASH in male mice through affecting cyclooxygenase-2/ Prostaglandin E2 (COX-2/PEG2) pathway and Matrix Metalloproteinase-9 (MMP-9). Methods: In this study, 24 C57/BL6 male mice were used. They were divided into four groups of 6 including; Control, RA, NASH, and NASH+RA. The NASH was induced by a methionine/choline-deficient diet for 8 weeks. The RA was administrated intraperitoneally and daily for 8 weeks. After 8 weeks, the animals were sacrificed and their liver was removed. hematoxylin and eosin staining was preformed for histological evaluation and real-time PCR and ELISA assays were used for molecular studies. Results: The RA significantly reduced hepatic steatosis and inflammation as well as the expression of MMP-9 and COX-2 which led to the significant reduction of PEG2 level. Conclusion: It seems that RA can reduce liver inflammation and thereby attenuate NASH in male mice by reducing the expression of COX-2 enzyme and MMP-9 and the concentration of PEG2.

Background and Objectives: Non-Alcoholic Steatohepatitis (NASH) is a serious and increasing liver disease, which develops into cirrhosis, fibrosis, and hepatocellular carcinoma. Rosmarinic Acid (RA) is a powerful antioxidant and anti-inflammatory compound. Therefore, this study aimed to assess the role of RA on a mouse model of NASH-induced liver fibrosis. Methods In this research, C57/BL6 mice were divided into 4 equal groups, as follows: the control, RA, NASH, and NASH+RA groups. In the third and fourth groups, NASH was induced by Methionine-Choline Deficient (MCD) diet for 8 weeks. In the RA and NASH+RA group, RA was intraperitoneally injected daily for 8 weeks in mice. After 8 weeks, the explored animals were sacrificed and the blood and liver samples were obtained. Then, Trichrome-Masson staining, serum, and molecular analyses were performed. Results After RA administration, the plasma levels of ALT and AST decreased. RA administration also reduced TGFβ and α-SMA genes expression. Finally, the histopathological evaluation revealed that RA administration decreased NASH-induced liver fibrosis. Conclusion It seems that RA administration improves NASH-induced liver fibrosis through the inhibition of the α-SMA/ TGF-β signaling pathway.

Background & Aim: Cholestasis is a type of liver disease due to structural damage and dysfunction of hepatobiliary system which at first results in accumulation of bile acids and other toxins in plasma and hepatic tissue. The aim of the current study was to investigate the possible hepatoprotective effects of rosmarinic acid against oxidative stress and liver injury in bile duct ligation (BDL)- induced cholestatic rats. Methods: In the present experimental study, twenty-four male Wistar rats (200±25 g) were randomly divided into three groups; control (N=6), cholestatic (N=9), cholestatic + rosmarinic acid at dose of 20 mg/kg/day (N=9). Biochemical tests (including aspartate amino transferase, AST; alanine amino transferase, ALT; alkaline phosphatase, ALP), oxidative stress markers (such as protein carbonyl, PCO; total thiol, TSH and ferric reducing antioxidant capacity; FRAP) and antioxidant enzymes (including catalase, CAT; super oxide dismutase, SOD; and glutathione peroxidase, GPx) activity were estimated. Also, hematoxylin and eosin staining were determined in the hepatic tissue. Results: There was a significant increase in AST, ALT, ALP and CAT activity, as well as plasma PCO and FRAP level in cholestatic group as compared to control rats, while the level of TSH, FRAP and GPX in hepatic tissue significantly decreased (P

Background: Rosemarinic acid is a phenolic compound that has neuroprotective properties. It has beneficial effect in neurological diseases such as Parkinson's and Alzheimer's. Rosmarinic acid increases the expression of neurotrophic factors such as brain-derived neurotrophic factor (BDNF), which can contribute in neuronal differentiation of stem cells. Methods: After isolation and proliferation, Wharton’s jelly stem cells were placed in inductive culture medium containing Rosmarinic acid. MTT assay was used to evaluate toxicity. After 4 days, induction of neuronal differentiation in Wharton’s jelly stem cells was evaluated using real-time polymerase chain reaction (real-time PCR) via analyzing the expression of Nestin and β-Tubulin III genes. Findings: MTT assay showed was no significant difference in viability between cells cultured in culture medium with Rosmarinic acid and control group (P < 0.05). Real-time PCR showed that adding Rosmarinic acid to culture medium increased the expression of Nestin and β-Tubulin III genes (P < 0.05). Conclusion: Increasing the expression of β-Tubulin III and Nestin, when there is Rosmarinic acid, may indicate a greater induction of neuronal differentiation in Wharton’s jelly stem cells. The results show that Rosmarinic acid induces the neuronal differentiation of Wharton’s jelly stem cells.

Melissa officinalis is a medicinal plant belong to lamiacea family. This plant has been cultivated in many parts of the world due to its therapeutic effects. This study was conducted to improve antioxidant activities of proliferated shoots from tissue culture. The seeds of plant were cultured in MS hormone free medium in order to obtain seedlings. Then the shoots were transfer to MS medium supplemented with 2 mg/ L BAP.After 45 days salicylic acid (SA) was added to the medium at concentrations of 0, 50, 100 and 200 µM. The antioxidant activity and phenolics, flavonoids and rosmarinic acid content in proliferated shoots were evaluated 4,7,10 and 14 days after treatment. As a result the highest free radical scavenging and reducing power activity, as well as the highest value of total phenolic and rosmarinic acid were observed in shoots after 14 days of treatment with 100 µM salicylic acid. The elevated level of superoxide anion scavenging activity and total flavonoids were obtained from the shoots treated with 50 µM salicylic acid for 14 days. Over all treatment with100 µM salicylic acid for 14 days was better in order to antioxidant activity and compounds with recognized antioxidant activity.

Salvia leriifolia Benth. is one of the native Iranian medicinal plants which has been received attention in recent years due to its numerous therapeutic properties. The pharmaceutical properties of this species have been attributed to the presence of phenolic compounds, especially phenolic acids. The present study investigated the effect of plant age (phenology) on the gene expression and activity of phenolic acid-biosynthetic enzymes. Plant seeds were collected from Torbat-e-Heydariyeh (Khorasan Razavi province, Iran) and planted under greenhouse conditions. Leaves were sampled at 8-, 16- and 24-leaf stages of the growth period. Total contents of phenols, flavonoids, and phenolic acids were measured using spectrophotometry, and the phenolic acid profile was determined by high-performance liquid chromatography (HPLC). The activities of phenylalanine ammonia-lyase (PAL) and tyrosine aminotransferase (TAT) were measured by spectrophotometry, and the activity of rosmarinic acid synthase (RAS) was evaluated by HPLC. The relative expression of the corresponding genes was quantified by RT-PCR. The results showed that the content of all phenolic compounds and the activities of TAT and RAS enzymes/genes increased significantly (P≤0.05) with increasing plant age. At the 24-leaf stage, the total content of phenols, flavonoids, and phenolic acids were 3.47-, 2.80-, and 7.78-fold of those measured at the 8-leaf stage, respectively. The concentration of rosmarinic acid and caffeic acid (0.69 and 0.36 mg/g DW at the 8-leaf stage, respectively) increased by 3.41- and 4.05-fold during the vegetative growth, respectively. Lithospermic acid and salvianolic acids had a smaller share of total phenolic acids (0.01-0.06 mg/g DW at the 8-leaf stage), and their contents increased 2- to 10-fold with increasing plant age. Also, a strong positive correlation was observed between plant age and phenolic acid accumulation and between plant age and the activity and gene expression of TAT and RAS. TAT enzyme might play the main role in the biosynthesis of rosmarinic acid compared to PAL. [ABSTRACT FROM AUTHOR]

It was the first time that hairy roots were initiated from Salvia reuterana by infection with Agrobacterium rhizogenes strain ATTC 15834. Confirmatory studies were carried out by direct detection of inserted T-DNA by the polymerase chain reaction. These hairy root cultures had the ability to produce rosmarinic acid. The effect of six different basic media including B5، ½ B5، MS، ½ MS، White’s and WPM on the root growth and rosmarinic acid production was studied. Results showed that maximum fresh weight (41.4 g/L-1) and dry weight (3.7 g/L-1) were found in MS medium. Despite the maximum rosmarinic acid production (52.2 mg/g DW) was achieved in B5 medium, the highest amount of rosmarinic acid yield (0.13 g/L-1) was observed in MS medium. Therefore MS medium was suggested as the best culture medium for growth and rosmarinic acid production in hairy root culture of Salvia reuterana.

Medicinal Plants are almost reach sources of natural antioxidants such as terpenoids and phenolic compounds and have great potential as an alternative for synthetic antioxidants against oxidative stresses. Peppermint (Mentha piperita) infusion is a valuable worldwide source of antioxidants. The antioxidant property can be enhanced by inducing abiotic stresses. This experiment was conducted to evaluate prolong (4 months) water deficit stress (no stress, mild stress and severe stress as 100, 75 and 50% of field capacity, respectively) on cultivated peppermint on plant growth, secondary metabolite profile and antioxidant capacity of peppermint infusions. Both water deficit stress treatment decresed plant height, leaf wet and dry weight and leaf size significantly. Also, water deficit stress increased antioxidant capacity, total phenolic and flavonoid contents significantly. Some phenolic compounds such as quercetin, coumaric acid and luteolin were detected only in water-deficit conditions. Also, the amount of some identified amino acids and unsaturated fatty acids were changed under water deficit stress. Therefore, inducing water stress can enhance the biological value of peppermint and improve bioactive compounds and the antioxidant capacity of peppermint extract. [ABSTRACT FROM AUTHOR]

Background and Objective: Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and results from the extracellular accumulation of -amyloid peptides and the resulting neuronal dysfunction. In this study, the role of nicotinic acetylcholine receptors, protein kinase B (PKB) and protein kinase M (PKM) were evaluated in order to examine the mechanism of the protective effects of rosmarinic acid in a rat model of Alzheimer's disease. Materials and Methods: Animals were divided into 6 groups consisting of 1) Sham, 2) Beta amyloid, 3) Rosmarinic acid pretreated beta amyloid (25 mg/kg), 4-6) Rosmarinic acid and PKM inhibitor, PKB inhibitor and acetylcholine receptor inhibitor pretreated beta amyloid. Two weeks post-surgery, behavioral (alternation percent in Y maze and step through latency in passive avoidance task) and histochemical (hippocampal malondialdehyde and neuronal density measurement) studies were performed. Results: Pretreatment of beta amyloid animals with rosmarinic acid considerably alleviated the behavioral and histochemical disturbances related to the hippocampus. In this group, nicotinic acetylcholine receptors and PKB inhibitors decreased step through latency (p<0.001) and increased hippocampal malondialdehyde levels (p<0.001). In addition, PKB inhibitors decreased hippocampal neuronal density in rosmarinic acid pretreated beta amyloid rats (p<0.05). Conclusion: Based on the findings of this study, it seems that in this experimental model of Alzheimer's disease the protective effects of rosmarinic acid were derived from its antioxidant properties and partially via nicotinic acetylcholine receptors, PKB and PKM. [ABSTRACT FROM AUTHOR]