Protective Effects Of Rosmarinic Acid Research Articles

Investigation of the role of rosmarinic acid treatment in regulating inflammation, cell damage, and angiogenesis in rat ovarian torsion and detorsion models.

Purpose To investigate the protective effect of rosmarinic acid (RA) in ovarian ischemia/reperfusion injury using biochemical, histopathological, and immunohistochemical methods.Methods Wistar female rats (n = 32) were randomly divided into four groups: control, ischemia, ischemia-reperfusion, and ischemia-reperfusion with RA. Rosmarinic acid was given at a dose of 50 mg/kg by oral gavage three hours after reperfusion. Malondialdehyde (MDA) levels and glutathione peroxidase (GSH-Px) activities were determined in the ovary tissue homogenates for each rat.Results In the ischemia-reperfusion with RA group, the epithelial cells are regularly regulated at the periphery, and the degenerative changes in preantral and antral follicle cells are reduced. Follicle cells and cells in the corpus luteum showed a decrease in vascular endothelial growth factor (VEGF) expression, while VEGF demonstrated a positive reaction in vascular endothelial cells and stromal cells. The TNF-α expression due to the decreased degenerative effect and inflammation was positive in the macrophage cells. The expression of caspase-3 as an apoptosis change was negative in antral follicle cells and granular cells around the antral follicle.Conclusion Different doses of RA may be useful in preventing ischemic damage after vascularization, inflammation, and apoptotic development after ischemia/reperfusion.

Polyphenol Compounds Attenuate High‐Dose PUFA‐Induced Oxidative Damage in Adipocytes

Although polyunsaturated fatty acids (PUFAs) are beneficial fatty acids, their excessive deposition can easily lead to lipid‐induced oxidation damage. It has recently been shown that diets rich in particular polyphenols may improve the oxidative status of tissues with high PUFA content. However, the underlying mechanism for this remains elusive. Therefore, a model is created of high‐dose PUFA injury in adipocytes, which investigates the effects of rosmarinic acid (RA) and caffeic acid (CA) on the alleviation of oxidative damage induced by high doses of PUFAs. It is observed that high‐dose linolenic acids (ALA) enhance lipid oxidation, inflammation, and autophagy in adipocytes. However, RA and CA attenuate the high‐dose ALA‐enhanced expression of inflammatory cytokines and microtubule‐associated protein 1, light chain 3, beta (MAP1LC3B). In addition, they reduce the intracellular levels of malondialdehyde (MDA) that are elevated by high doses of ALA, and modulate the activities of superoxide dismutase (SOD), catalase antioxidant (CAT), and glutathione peroxidase (GSH‐Px) enzymes. The protective effects of RA and CA on adipocyte oxidative stress are in part associated with their capacity to improve the activities of antioxidant enzymes and exert free radical‐scavenging activity. Collectively, these results suggest that RA and CA may have potential benefits in protecting adipose cells from high‐dose PUFA‐induced oxidative damage.Practical Applications: It is known that a diet rich in PUFAs has beneficial effects on cardiovascular disease. However, an accumulation of unsaturated fatty acids in tissues is more susceptible to lipid oxidation. In this study, it is found that polyphenols have the potential to protect adipose cells from high‐dose PUFAs‐induced damage. It has also been suggested that the consumption of a diet enriched in polyphenols could be beneficial for the prevention of lipid peroxidation and maintaining the balance between oxidative and anti‐oxidative processes.Polyphenols suppress the formation of lipid peroxy radical species. The process of lipid peroxidation consists of initiation, propagation, and termination. In the termination reaction, polyphenols may donate a hydrogen atom to the lipid radical, resulting in the termination of lipid peroxy radical species formation. In addition, polyphenols may improve the activity of antioxidant enzymes, thereby suppressing the formation of lipid peroxy radical species.

Protective Effects of Rosmarinic Acid against Selenite-Induced Cataract and Oxidative Damage in Rats.

Cataracts are the major cause of blindness and are associated with oxidative damage of the lens. In the present study, the aim was to evaluate the protective effects of rosmarinic acid on selenite-induced cataractogenesis in Sprague-Dawley rat pups. The animals were randomly divided into five groups, each of which consisted of 10 rat pups. Group I served as normal control (vehicle administration). For testing cataract induction, animals of Groups II, III, IV, and V were administered a single subcutaneous injection of sodium selenite (2.46 mg/kg body weight) on postpartum day 12. After sodium selenite intoxication, Group II served as control selenite. From the 11th day through the 17th day, Groups III-V received rosmarinic acid intraperitoneally at doses of 5, 10, and 50 mg/kg, respectively. On postpartum day 24, the rat pups were examined for cataract formation, and the lenses were isolated for further analysis of proteins and oxidative damage indicators. Selenite caused significant (p < 0.05) cataract formation. Through the effects of selenite, the protein expressions of filensin and calpain 2 were reduced, and the calcium concentrations, the level of lipid peroxidation (TBARS), and inflammation indicators (iNOS, COX-2, and NFκB) were upregulated. Furthermore, the protein expression of the antioxidant status (Nrf2, SOD, HO-1, and NQO1), the antioxidant enzymes activities (GSH-Px, GSH-Rd, and catalase), and the GSH levels were downregulated. In contrast, treatment with rosmarinic acid could significantly (p < 0.05) ameliorate cataract formation and oxidative damage in the lens. Moreover, rosmarinic acid administration significantly increased the protein expressions of filensin, calpain 2, Nrf2, SOD, HO-1, and NQO1, the antioxidant enzymes activities, and the GSH level, in addition to reducing the calcium, lipid peroxidation, and inflammation indicators in the lens. Taken together, rosmarinic acid is a prospective anti-cataract agent that probably delays the onset and progression of cataracts induced by sodium selenite.

Protective effect of rosmarinic acid and carnosic acid against streptozotocin-induced oxidation, glycation, inflammation and microbiota imbalance in diabetic rats.

This study evaluated the protective effects of two rosemary components, rosmarinic acid (RA) and carnosic acid (CA), against hypoglycemia, hyperlipidemia, oxidative stress and an imbalanced gut microbiota architecture in diabetic rats. Treatment with RA and CA (30 mg kg-1) decreased the levels of fasting plasma glucose (23.7%, 15.6%), total cholesterol (30.4%, 14.1%) and triglyceride (65.7%, 47.8%) at 15 weeks. RA and CA also exhibited an anti-oxidative and anti-glycative effect by lowering the formation of malondialdehyde and advanced glycation end products. In addition, they showed protective effects against tissue damage and inflammation in the abdominal aorta, based on microscopic observations and the analysis of protein expression. Finally, the prebiotic effects of RA and CA on gut microbiota were demonstrated by increasing the population of diabetes-resistant bacteria and decreasing the amounts of diabetes-sensitive bacteria. Overall, RA showed a stronger protective effect than CA in mitigating diabetic symptoms in rats.

Protective effects of rosmarinic acid against hydrogen peroxide‑induced cellular senescence and the inflammatory response in normal human dermal fibroblasts.

Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that induces numerous cellular events, including cellular senescence and inflammatory responses. Therefore, the aim of this study was to investigate the protective effect of Rosmarinic acid (RA) in H2O2‑induced oxidative stress in normal human dermal fibroblasts (NHDFs). Cytotoxicity assays were performed using a water‑soluble tetrazolium salt, and senescence‑associated β‑galactosidase activity was determined to investigate the proportion of senescent cells. Antioxidant capacities were evaluated via H2O2‑scavenging activity, reverse transcription‑quantitative polymerase chain reaction, NRF2 luciferase reporter gene activity and intracellular ROS scavenging assays. Cytokine‑coded gene expression analysis and nuclear factor‑κB luciferase activity were determined to verify the anti‑inflammatory effect of RA. As a result, the present study demonstrated that rosmarinic acid inhibited H2O2‑induced oxidative stress and inflammatory responses in normal human dermal fibroblasts. Initially, the doses of RA that exerted minimal cytotoxic effects in NHDFs were determined using a cytotoxicity assay. Subsequently, pretreatment with the appropriate doses of RA significantly reversed the H2O2‑induced decrease in NHDF cell viability and decreased cellular senescence of NHDFs. In addition, RA inhibited H2O2‑induced ROS production in NHDFs, as determined by a ROS scavenging assay. The protective effects of RA were mediated by the inhibition of nuclear factor erythroid‑derived2‑like2, a transcription factor that functions as a key regulator of redox sensitivity. Furthermore, RA suppressed H2O2‑induced inflammation in NHDFs and significantly rescued H2O2‑induced downregulation of sirtuin1. RA also inhibited nuclear factor (NF)‑κB transcriptional activity and the expression of NF‑κB target genes, including tumor necrosis factor‑α and interleukin‑6, in H2O2‑exposed NHDFs. Taken together, these data indicate that RA inhibits H2O2‑induced cellular damage in NHDFs.

Changes of auditory event-related potentials in ovariectomized rats injected with d-galactose: Protective role of rosmarinic acid

Rosmarinic acid (RA), which has multiple bioactive properties, might be a useful agent for protecting central nervous system against age related alterations. In this context, the purpose of the present study was to investigate possible protective effects of RA on mismatch negativity (MMN) component of auditory event-related potentials (AERPs) as an indicator of auditory discrimination and echoic memory in the ovariectomized (OVX) rats injected with d-galactose combined with neurochemical and histological analyses. Ninety female Wistar rats were randomly divided into six groups: sham control (S); RA-treated (R); OVX (O); OVX+RA-treated (OR); OVX+d-galactose-treated (OD); OVX+d-galactose+RA-treated (ODR). Eight weeks later, MMN responses were recorded using the oddball condition. An amplitude reduction of some components of AERPs was observed due to ovariectomy with or without d-galactose administiration and these reduction patterns were diverse for different electrode locations. MMN amplitudes were significantly lower over temporal and right frontal locations in the O and OD groups versus the S and R groups, which was accompanied by increased thiobarbituric acid reactive substances (TBARS) and hydroxy-2-nonenal (4-HNE) levels. RA treatment significantly increased AERP/MMN amplitudes and lowered the TBARS/4-HNE levels in the OR and ODR groups versus the O and OD groups, respectively. Our findings support the potential benefit of RA in the prevention of auditory distortion related to the estrogen deficiency and d-galactose administration at least partly by antioxidant actions.

The Protective Effect of Rosmarinic Acid on the Aluminum of Dementia Inducer

The Protective Effect of Rosmarinic Acid on the Aluminum of Dementia Inducer

RETRACTED: Rosmarinic acid protects rat hippocampal neurons from cerebral ischemia/reperfusion injury via the Akt/JNK3/caspase-3 signaling pathway

Cerebral ischemia/reperfusion injury can result in neuronal death, which further results in brain damage and can even lead to death. Although recent studies showed that rosmarinic acid (RA) exerts neuroprotective effects and attenuates ischemia-induced brain injury and neuronal cell death, little is known about the precise mechanisms that occur during cerebral ischemia/reperfusion (I/R). Therefore, the aim of this study was to examine the underlying mechanism of the neuroprotective effects of RA against ischemic brain injury induced by cerebral I/R. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats. We randomly divided rats into five groups: sham, I/R, I/R+RA, I/R+Vehicle and I/R+RA+LY. Open-field, closed-field and Morris water maze tests were carried our separately to examine the anxiety and cognitive behavior of each group. Cresyl violet staining was used to examine the survival of hippocampal CA1 pyramidal neurons. The levels of p-Akt, p-JNK3 and cleaved caspase-3 in the hippocampus were also examined by Western blotting. Our results showed that administration of RA protected locomotive ability, relieved anxiety behavior and protected cognitive ability in cerebral I/R-injured rats. Additionally, RA significantly protected neurons in the hippocampal CA1 region against cerebral I/R-induced damage. Furthermore, RA increased the phosphorylation of Akt1, downregulated the phosphorylation of JNK3 and reduced the expression of cleaved caspase-3. Finally, the Akt inhibitor LY294002 reversed all the protective effects of RA, indicating that RA protects neurons in the hippocampal CA1 region from ischemic damage through the Akt/JNK3/caspase-3 signaling pathway.

Therapeutic effects of rosmarinic acid on airway responses in a murine model of asthma

Rosmarinic acid (RA) is an active component of a traditional Chinese herbal medicine. Previously, we reported that RA exerted a strong anti-inflammatory effect in a mouse acute lung injury model. Therefore, we hypothesized that RA might also have potential therapeutic effects in a murine model of asthma. In this study, we aimed to evaluate the anti-asthmatic activity of RA and explored its possible molecular mechanisms of action. Female BALB/c mice that had been sensitized to and challenged with ovalbumin (Ova) were treated with RA (20mg/kg) 1h after challenge. The results showed that RA greatly diminished the number of inflammatory cells and the production of Th2 cytokines in the bronchoalveolar lavage fluid (BALF); significantly reduced the secretion of total IgE, Ova-specific IgE, and eotaxin; and markedly ameliorated airway hyperresponsiveness (AHR) compared with Ova-induced mice. Histological studies further revealed that RA substantially decreased inflammatory cells infiltration and mucus hypersecretion compared with Ova-induced mice. Moreover, our results suggested that the protective effects of RA were mediated by the inhibition of JNK and p38 MAPK phosphorylation and nuclear factor-κB (NF-κB) activation. Furthermore, RA treatment resulted in a significant reduction in the mRNA expression of AMCase, CCL11, CCR3, Ym2 and E-selectin in lung tissue. These findings suggest that RA may effectively delay the development of airway inflammation and could thus be used as a therapy for allergic asthma.

Protective effects of rosmarinic acid against radiation-induced damage to the hematopoietic system in mice.

Rosmarinic acid (RA) is an ester of caffeic acid and 3, 4-dihydroxyphenyl lactic acid. It is a potent antioxidant that functions by scavenging free radicals. Here, we used a 30-day survival assay to investigate the radioprotective effects of RA. Mice were treated with RA once per day for 10 consecutive days starting at 3 days before gamma irradiation at 7.5 Gy until 7 days post irradiation. Mice treated with 100 and 200 mg/kg body weight (bw) of RA had 30-day survival rates of 89% and 72%, respectively, compared with 32% in the control group, and the differences were statistically significant (P = 0.0008 and 0.0421, respectively). Spleen colony–forming units (CFU-S), the number of nucleated cells in the bone marrow (BMNC), bone marrow DNA content, and hematological parameters of the peripheral blood were measured to investigate the radioprotective effect of RA on the hematopoietic system. The treatment groups that received RA at 50, 100 and 150 mg/kg bw and whole-body exposure to 5.5 Gy of 137Cs γ- radiation had significantly higher CFU-S, BMNC and DNA content than the irradiation-only group. Assessment of hematological parameters in the peripheral blood showed that the treatment groups receiving RA at doses of 50, 100 and 150 mg/kg bw had higher white blood cell counts, hemoglobin and platelets than the radiation-only group. These results suggested that the administration of RA promoted the recovery of peripheral blood cells in irradiated mice.

Rosmarinic Acid Attenuates Airway Inflammation and Hyperresponsiveness in a Murine Model of Asthma.

Rosmarinic acid (RA) has numerous pharmacologic effects, including anti-oxidant, anti-inflammatory, and analgesic effects. This study aimed to evaluate the preventive activity of RA in a murine model of asthma and to investigate its possible molecular mechanisms. Female BALB/c mice sensitized and challenged with ovalbumin (Ova) were pretreated with RA (5, 10 or 20 mg/kg) at 1 h before Ova challenge. The results demonstrated that RA markedly inhibited increases in inflammatory cells and Th2 cytokines in the bronchoalveolar lavage fluid (BALF), significantly reduced the total IgE and Ova-specific IgE concentrations, and greatly ameliorated airway hyperresponsiveness (AHR) compared with the control Ova-induced mice. Histological analyses showed that RA substantially decreased the number of inflammatory cells and mucus hypersecretion in the airway. In addition, our results suggested that the protective effects of RA might be mediated by the suppression of ERK, JNK and p38 phosphorylation and activation of nuclear factor-κB (NF-κB). Furthermore, RA pretreatment resulted in a noticeable reduction in AMCase, CCL11, CCR3, Ym2 and E-selectin mRNA expression in lung tissues. These findings suggest that RA may effectively delay the progression of airway inflammation.

Aging as a Precipitating Factor in Chronic Restraint Stress-Induced Tau Aggregation Pathology, and the Protective Effects of Rosmarinic Acid

Stress is an important risk factor of Alzheimer's disease (AD). It has been evidenced that stress could induce tau phosphorylation and increase tau insolubility in brain; however, little is known about the interactional effect of stress with aging on tauopathy. Therefore, we explored the effects of aging on stress-induced tauopathy and the potential mechanism in mouse model of chronic restraint stress (CRS). Here we found that in general, the level of phosphorylated tau (P-tau) was higher in brain of middle-aged mice than that in adult mice under physiological conditions. CRS-induced tau phosphorylation and its insolubility were more prominent in middle-aged mice. The increase of AT8-labeled insoluble P-tau was dramatic in middle-aged mice, which was highly ubiquitinated but did not form PHF structures. The levels of chaperones were relatively lower in middle-aged mice brain; CRS further reduced the expression, especially for HDJ2/HSP40. CRS also suppressed the expression of Pin1, the peptidylprolyl cis/trans isomerase, in middle-aged mice but not in adult mice. Downregulation of HSP40 or Pin1 caused an increase of transfected extraneous tau in 293 cells. Rosmarinic acid (RA) could effectively suppress the elevation of P-tau and insoluble P-tau formation induced by CRS, and reversed the abnormal changes of chaperones and Pin1 particularly in middle-aged mice. Taken together, our findings provided evidence that aging could be a promoting factor in stress-induced tauopathy, which was relevant with malregulation of chaperones and Pin1, and RA might be a promising beneficial agent for stress-induced tauopathy.

Protective effect of rosmarinic acid against oxidative stress biomarkers in liver and kidney of strepotozotocin-induced diabetic rats.

In the present study, we investigated the efficiency of rosmarinic acid (RA) in preventing the alteration of oxidative parameters in the liver and kidney of diabetic rats induced by streptozotocin (STZ). The animals were divided into six groups (n = 8): control, ethanol, RA 10 mg/kg, diabetic, diabetic/ethanol, and diabetic/RA 10 mg/kg. After 3 weeks of treatment, we found that TBARS levels in liver and kidney were significantly increased in the diabetic/saline group and the administration of RA prevented this increase in the liver and kidney (P < 0.05). Diabetes caused a significant decrease in the activity of superoxide dismutase (SOD) and catalase (CAT) in the diabetes/saline group (P < 0.05). However, the treatment with 10 mg/kg RA (antioxidant) prevented this alteration in SOD and CAT activity in the diabetic RA group (P < 0.05). In addition, RA reverses the decrease in ascorbic acid and non-protein-thiol (NPSH) levels in diabetic rats. The treatment with RA also prevented the decrease in the Delta-aminolevulinic acid dehydratase (ALA-D) activity in the liver and kidney of diabetic rats. Furthermore, RA did not have any effect on glycemic levels. These results indicate that RA effectively reduced the oxidative stress induced by STZ, suggesting that RA is a potential candidate for the prevention and treatment of pathological conditions in diabetic models.

Rosmarinic acid up-regulates the noise-activated Nrf2/HO-1 pathway and protects against noise-induced injury in rat cochlea

Noise-induced hearing loss depends on progressive increase of reactive oxygen species and lipoperoxidative damage in conjunction with the imbalance of antioxidant defenses. The redox-sensitive transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in the regulation of cellular defenses against oxidative stress, including heme oxygenase-1 (HO-1) activation. In this work we describe a link between cochlear oxidative stress damage, induced by noise exposure, and the activation of the Nrf2/HO-1 pathway. In our model, noise induces superoxide production and overexpression of the lipid peroxidation marker 4-hydroxy-nonenals (4-HNE). To face the oxidative stress, the endogenous defense system is activated as well, as shown by the slight activation of superoxide dismutases (SODs). In addition, we observed the activation of the Nrf2/HO-1 pathway after noise exposure. Nrf2 appears to promote the maintenance of cellular homeostasis under stress conditions. However, in this model the endogenous antioxidant system fails to counteract noise-induced cell damage and its activation is not effective enough in preventing cochlear damage. The herb-derived phenol rosmarinic acid (RA) attenuates noise-induced hearing loss, reducing threshold shift, and promotes hair cell survival. In fact, RA enhances the endogenous antioxidant defenses, as shown by decreased superoxide production, reduced expression of 4-HNE, and up-regulation of SODs. Interestingly, RA potentiates the Nrf2/HO-1 signaling pathway, as shown by immunohistochemical and Western blot analyses. Thus, protective effects of RA are associated with the induction/activation of the Nrf2-ARE signaling pathway in addition to RA direct scavenging capability.

The cellular protective effects of rosmarinic acid: from bench to bedside.

Rosemary (Rosmarinus officinalis L.) is one of the most common household herbs, used as spices in a variety of foods, and employed in traditional medicine for its healing properties. Rosemary is a rich source of active antioxidant constituents such as phenolic diterpenes, flavonoids and phenolic acids. Caffeic acid and rosmarinic acid are the most important bioactive constituents. Rosmarinic acid is the ester of caffeic acid and 3,4-dihydroxyphenyllactic acid and is widely identified in different plant species. Chemical structure of rosmarinic acid contains two phenolic rings: one of them is derived from phenylalanine via caffeic acid and the other from tyrosine via dihydroxyphenyl-lactic acid. Its large-scale production is obtained from plant cell cultures of Coleus blumei Benth. It is easily absorbed through gastrointestinal tract as well as the skin. Rosmarinic acid is one of the most important and well known natural antioxidant compounds, which possesses neuroprotective effects in different models of neuroinflammation, neurodegeneration, as well as chemicalinduced neurotoxicity and oxidative stress. Therefore, in present review, we aim to discuss about chemistry, sources, biotechnological production and neuroprotective actions of rosmarinic acid with emphasis on its possible molecular mechanisms of neuroprotection.

Protective effects of rosmarinic acid on sepsis-induced DNA damage in the liver of Wistar albino rats

Event Abstract Back to Event Protective effects of rosmarinic acid on sepsis-induced DNA damage in the liver of Wistar albino rats Hatice G. Goktas1, 2*, Merve Bacanli1, Sevtap Aydin1, Gokce Taner3, Tolga Sahin4, Arif Ahmet Başaran5 and Nursen Basaran1 1 Hacettepe University Faculty of Pharmacy, Department of Toxicology, Turkey 2 Cukurova University Faculty of Pharmacy, Department of Toxicology, Turkey 3 Gazi University, Faculty of Science, Biology, Turkey 4 Hacettepe University Faculty of Kastamonu Medicine, Surgery, Turkey 5 Hacettepe University Faculty of Pharmacy, Pharmacognosy, Turkey Sepsis is an imbalance between pro and anti-inflammatory responses. Sepsis induced multiple organ failure that is associated with mortality is characterized by liver, renal, cardiovascular and pulmonary dysfunction and reactive oxygen species (ROS) are believed to be involved in the development of sepsis. Plant polyphenols may act as antioxidants by different mechanisms such as free radical scavenging, metal chelation and protein binding. Data indicates possible beneficial effects of plant derived phenolic compounds against sepsis. Rosmarinic acid (RA) (α-O-caffeoyl-3,4-dihydroxyphenyllactic acid) is a phenolic compound commonly found in various plants such as Rosmarinus officinalis (rosemary), Origanum vulgare (oregano), Thymus vulgaris (thyme), Mentha spicata (spearmint), Perilla frutescens (perilla), Ocimum basilicum (sweet basil) and several other medicinal plants. It has been shown that RA has many biological activities including antioxidant, anti-inflammatory, antiallergic, anticancer and actimicrobial and is widely used in cosmetic and food industry. In the present study, we aimed to determine the protective effects of RA against the oxidative DNA damage induced by sepsis in Wistar albino rats. The rats were divided into four groups; sham, sepsis induced, RA-treated, RA treated and sepsis induced groups. Wistar rats were subjected to sepsis by cecal ligation puncture. The liver tissues were carefully dissected from their attachments and totally excised. The concentrations of the hepatic tissue cells were adjusted to approximately 2 x 106 cells/ml. Standard and formamidopyrimidine-DNA glycosylase (Fpg) modified comet assay described by Singh et al were used. There were no statistically significant differences in terms of tail length, tail intensity and tail moment between the sham group and the RA-treated groups (p>0.05). The DNA damage was found significantly higher in the sepsis-induced group compared to the sham group (p<0.05). RA treatment in the sepsis-induced group was found to decrease the DNA damage significantly (p<0.05). Similarly in the Fpg-modified comet assay, there were no statistically significant differences in terms of tail length, tail intensity and tail moment between the sham group and the RA-treated group (p>0.05), and the DNA damage was found significantly higher in the sepsis-induced group compared to the sham group (p<0.05). RA treatment in the sepsis-induced group was found to decrease the DNA damage significantly (p<0.05). In conclusion, RA might have a role in the prevention of sepsis-induced oxidative damage not only by decreasing the DNA damage but also by increasing DNA repair capacity of the animals.

Anti-inflammatory effect of rosmarinic acid and an extract of Rosmarinus officinalis in rat models of local and systemic inflammation.

Rosmarinic acid is a polyphenolic compound and main constituent of Rosmarinus officinalis and has been shown to possess antioxidant and anti-inflammatory properties. We aimed to evaluate the anti-inflammatory properties of rosmarinic acid and of an extract of R. officinalis in local inflammation (carrageenin-induced paw oedema model in the rat), and further evaluate the protective effect of rosmarinic acid in rat models of systemic inflammation: liver ischaemia-reperfusion (I/R) and thermal injury models. In the local inflammation model, rosmarinic acid was administered at 10, 25 and 50 mg/kg (p.o.), and the extract was administered at 10 and 25 mg/kg (equivalent doses to rosmarinic acid groups) to male Wistar rats. Administration of rosmarinic acid and extract at the dose of 25 mg/kg reduced paw oedema at 6 hr by over 60%, exhibiting a dose-response effect, suggesting that rosmarinic was the main contributor to the anti-inflammatory effect. In the liver I/R model, rosmarinic acid was administered at 25 mg/kg (i.v.) 30 min. prior to the induction of ischaemia and led to the significant reduction in the serum concentration of transaminases (AST and ALT) and LDH. In the thermal injury model, rosmarinic acid was administered at 25 mg/kg (i.v.) 5 min. prior to the induction of injury and significantly reduced multi-organ dysfunction markers (liver, kidney, lung) by modulating NF-κB and metalloproteinase-9. For the first time, the anti-inflammatory potential of rosmarinic acid has been identified, as it causes a substantial reduction in inflammation, and we speculate that it might be useful in the pharmacological modulation of injuries associated to inflammation.

Protective Effects of Rosmarinic Acid on Doxorubicin-Induced Testicular Damage

Background: We investigated the protective effects of rosmarinic acid (RA) on testicular damage induced by doxorubicin (DXR) in rats. Methods: In total, 21 rats were divided into 3 groups: the control group that received no treatment, the DXR group that received intraperitoneal (i.p.) DXR on day 7 and the DXR + RA group that received intragastric RA for 10 days with i.p. DXR on day 7. The rats were sacrificed on day 11 for histological and biochemical analyses. To assess oxidative damage, glutathione peroxidase (GPx) and malondialdehyde (MDA) levels were measured. Results: The median modified Johnsen score of the DXR + RA group was higher than that of the DXR group (p = 0.002). The rats with the narrowest seminiferous tubules were in the DXR group (0.17 ± 0.03), and the difference between the DXR + RA and DXR groups was statistically significant (p = 0.002). The number of apoptotic cells in the DXR group was significantly higher than that in the control group, and there were significantly fewer apoptotic cells in the DXR + RA group than in the DXR group (p = 0.002). The MDA level was lowest in the control group and highest in the DXR group, and the level observed in the DXR + RA group significantly lower than that in the DXR group (p = 0.002). The GPx level was highest in the control group, with the level observed in the DXR + RA group significantly higher than that in the DXR group (p = 0.002). The testosterone level was lowest in the DXR group and highest in the control group, and that observed in the DXR + RA group was significantly higher than that in the DXR group (p = 0.018). Conclusions: RA can correct DXR-induced testicular damage through its antioxidant properties. However, the mechanism underlying the effects of RA requires further investigation, and long-term and comparative human studies are also needed.

Cr (VI) induced oxidative stress and toxicity in cultured cerebellar granule neurons at different stages of development and protective effect of Rosmarinic acid.

Chromium (Cr) is a widespread metal ion in the workplace, industrial effluent, and water. The toxicity of chromium (VI) on various organs including the liver, kidneys, and lung were studied, but little is known about neurotoxicity. In this study, neurotoxic effects of Cr (VI) have been investigated by cultured cerebellar granule neurons (CGNs). Immature and mature neurons were exposed to different concentrations of potassium dichromate for 24 h and cytotoxicity was measured by MTT assay. In addition, immature neurons were exposed for 5 days as regards cytotoxic effect in development stages. The reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and the protective effect of Rosmarinic acid on mature and immature neurons exposed to potassium dichromate, were measured. Furthermore, lipid peroxidation, glutathione peroxidase (GPx), and acetylcholinesterase activity in mature neurons were assessed following exposure to potassium dichromate. The results indicate that toxicity of Cr (VI) dependent on maturation steps. Cr (VI) was less toxic for immature neurons. Also, Cr (VI) induced MMP reduction and ROS production in both immature and mature neurons. In Cr (VI) treated neurons, increased lipid peroxidation and GPx activity but not acetylcholinesterase activity was observed. Interestingly, Rosmarinic acid, as a natural antioxidant, could protect mature but not immature neurons against Cr (VI) induced toxicity. Our findings revealed vulnerability of mature neurons to Cr (VI) induced toxicity and oxidative stress.

The protective effect of rosmarinic acid on hyperthermia-induced C2C12 muscle cells damage.

High temperature will cause animal tissues or cells damage. Rosmarinic acid (RA) is a good antioxidant and health care product, but the roles of RA in muscle cells damage and the mechanisms which caused by high temperature is still unknown. In this study, the roles of RA on hyperthermia-induced apoptosis and damage of C2C12 muscle cells were investigated. C2C12 cells were cultured in medium with different concentration (0, 25, 50, 100 µM) RA and treated in 42 °C high temperature to induce cellular apoptosis and damage. Then, these cells were analyzed effect of different dose of RA on cells apoptosis and damage. The results indicated that RA has protective effect on heat-stress induced cellular damage, and the cells have the higher cell viability at the dose of 50 µM RA by MTT assay. Hochest33342/PI double staining showed that the cellular apoptosis of C2C12 cells were decreased in the presence of selected 50 µM RA. Malondialdehyde formation and reactive oxygen species levels were also decreased significantly, but cellular superoxide dismutase activity was increased significantly in the presence of RA even in the condition of 42 °C. Meanwhile, Caspase-3 mRNA expression, Caspase-3 activity, and Bax/Bcl-2 ratio were reduced significantly, but the mRNA expression of Hsp72 was increased significantly in those hyperthermia-induced C2C12 cells in the presence of 50 µM RA. Taken together, the results at least discovered that RA has protective effects on hyperthermia-induced cellular apoptosis and damage of muscle cells by change the expression of stress-genes and increasing intracellular antioxidant capability.