PMID: 

Molecules. 2020 Apr 15 ;25(8). Epub 2020 Apr 15. PMID: 32326410

Abstract Title: 

Natural Compounds Rosmarinic Acid and Carvacrol Counteract Aluminium-Induced Oxidative Stress.

Abstract: 

Aluminum accumulation, glutathione (GSH) and malondialdehyde (MDA) concentrations as well as catalase (CAT) and superoxide dismutase (SOD) activities were determined in erythrocytes and brain and liver homogenates of BALB/c mice treated with Al(7.5 mg/kg/day (0.15 LD) as AlCl(37.08 mg/kg/day), whereas HCl (30.41 mg/kg/day) was used as Clcontrol, the treatments were performed for 21 days, i.p., in the presence and absence of rosmarinic acid (0.2805 mg/kg/day (0.05 LD), 21 days, i.g.) or carvacrol (0.0405 mg/kg/day (0.05 LD), 21 days, i.g.). The treatment with AlClincreased GSH concentration in erythrocytes only slightly and had no effect on brain and liver homogenates. Rosmarinic acid and carvacrol strongly increased GSH concentration in erythrocytes but decreased it in brain and liver homogenates. However, AlCltreatment led to Al accumulation in mice blood, brain, and liver and induced oxidative stress, assessed based on MDA concentration in the brain and liver. Both rosmarinic acid and carvacrol were able to counteract the negative Al effect by decreasing its accumulation and protecting tissues from lipid peroxidation. AlCltreatment increased CAT activity in mice brain and liver homogenates, whereas the administration of either rosmarinic acid or carvacrol alone or in combination with AlClhad no significant effect on CAT activity. SOD activity remained unchanged after all the treatments in our study. We propose that natural herbal phenolic compounds rosmarinic acid and carvacrol could be used to protect brain and liver against aluminum induced oxidative stress leading to lipid peroxidation.

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PMID: 

Nutrients. 2020 Apr 22 ;12(4). Epub 2020 Apr 22. PMID: 32331258

Abstract Title: 

Lemon Balm and Its Constituent, Rosmarinic Acid, Alleviate Liver Damage in an Animal Model of Nonalcoholic Steatohepatitis.

Abstract: 

Nonalcoholic fatty liver disease (NAFLD) ranges in severity from hepatic steatosis to cirrhosis. Lemon balm and its major constituent, rosmarinic acid (RA), effectively improve the liver injury and obesity; however, their therapeutic effects on nonalcoholic steatohepatitis (NASH) are unknown. In this study, we investigated the effects of RA and a lemon balm extract (LBE) on NAFLD and liver fibrosis and elucidated their mechanisms. Palmitic acid (PA)-exposed HepG2 cells and db/db mice fed a methionine- and choline-deficient (MCD) diet were utilized to exhibit symptoms of human NASH. LBE and RA treatments alleviated the oxidative stress by increasing antioxidant enzymes and modulated lipid metabolism-related gene expression by the activation of adenosine monophosphate-activated protein kinase (AMPK) in vitro and in vivo. LBE and RA treatments inhibited the expression of genes involved in hepatic fibrosis and inflammation in vitro and in vivo. Together, LBE and RA could improve liver damage by non-alcoholic lipid accumulation and may be promising medications to treat NASH.

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Being overweight is an established risk factor for multiple diseases, and is now known to dramatically increase the risk of several cancers

PMID: 

Evid Based Complement Alternat Med. 2020 ;2020:6489159. Epub 2020 Apr 14. PMID: 32351599

Abstract Title: 

Lemon Balm Extracts Prevent Breast Cancer Progressionandon Chorioallantoic Membrane Assay.

Abstract: 

Breast cancer is the most frequently diagnosed malignant pathology, representing the primary cause of cancer death in women. Natural products are an appealing strategy to limit the progression of the disease. Targeting angiogenesis in breast cancer may positively impact on poor prognosis of breast cancer. As source of natural compounds, we investigated the leaves ofL. (MO), known as lemon balm, an aromatic plant that spontaneously grows in the South and Western areas of Romania, being traditionally recommended as anxiolytic, antispasmodic, or as digestive remedy. Our aim was to investigate the phytochemical profiling and the antiangiogenic and chemopreventive bioactivity of MO from Banat region, on breast cancer. Two ethanolic extracts of MO (MOE96 and MOE70) and one methanolic extract (MOM80) were subjected to polyphenol and triterpene profiling by HPLC-MS, and the antioxidant capacity was evaluated. The antiangiogenic potential was investigated using the chorioallantoic membrane assay (CAM). The MTT(3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide) assay was used to investigate the cytotoxic effects on MCF-7 and MDA-MB-231breast cancer cells, as well as on MCF-10A normal breast epithelial cells, while apoptosis was performed by DAPI staining. Rosmarinic acid (RA) and ursolic acid (UA) were revealed as dominant phytocompounds. The highest concentration in phytochemicals were found in MOM80; MOE96 was more concentrated in UA, while MOE70 extracted more RA. MOE96 inhibited cancer progression and angiogenesis in the in ovo CAM model using MDA-MB-231 cells, inhibiting breast cancer progression and angiogenesis for the MDA-MB-231 breast cancer cell line; no secondary tumoral areas were registered, indicative for a preventive effect against breast tumor cell invasiveness. The highest cell inhibitory activity was also exhibited by MOE96, in particular against the estrogen receptor positive MCF7 breast cancer cell line, with no cytotoxic effect on healthy cells. The estrogen receptor positive MCF7 cell line proved to be more sensitive to the extract antiproliferative activity than the triple negative MDA-MB-231 breast cancer cell line. Nevertheless, the chemopreventive potential of MOE96 extract is phenotype-dependent and is rather related to the apoptosis and antiangiogenic effects suggesting a multitargeted mechanism of action due to its multiple compound composition next to a concentration ratio of RA : UA in favor of UA.

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PMID: 

Mol Biol Rep. 2020 Apr 29. Epub 2020 Apr 29. PMID: 32350743

Abstract Title: 

The effects of rosmarinic acid on oxidative stress parameters and inflammatory cytokines in lipopolysaccharide-induced peripheral blood mononuclear cells.

Abstract: 

Rosmarinic acid (RA) is a potential herbal medicine and has received considerable attention due to its strong antioxidant properties. The aim of this study is to investigate the impact of RA on inflammation and oxidative stress induced by lipopolysaccharide (LPS) in peripheral blood mononuclear cells (PBMCs). PBMCs were pre-treated with various contents of RA (20, 40, 80 µM) for 24 h, then, stimulated with LPS (10 ng/ml) for more 6 h. ELISA and Real-time PCR were done to detect the levels of IL-6, TNF-α, COX-2, IL-1β and IL-10. Western blot was done to investigate the phosphorylated amounts of P65-NF-κB and JNK. Inflammatory cytokines and oxidant-antioxidant parameters were determined by colorimetric and ELISA methods. The results indicated that LPS augmented the protein levels of IL-6, TNF-α, and IL-1β cytokines as well as the mRNA levels of IL-6, TNF-α, IL-1β, COX-2, and IL-10 cytokines in in PBMCs. However, pretreatment with RA could reduce theimpact of LPS on inflammatory markers. In addition, RA inhibited P65-NF-κB and JNK phosphorylation. LPS also caused a decrease in antioxidant enzymes, total thiol, and total antioxidant capacity as well as an increment in malondialdehyde and nitric oxide metabolite contents that RA abrogated them.Collectively, our finding demonstrated that RA ameliorates LPS-induced inflammation in PBMCs. RA reduces oxidative stress by preventing lipid peroxidation and nitric oxide production as well as restarting the activity of the GPx and SOD enzymes. Furthermore, our findings indicated that RA was ableto protect PBMCs from inflammation via inhibiting the NF-κB and JNK MAPK pathways. This evidence shows a promising therapeutic role for RA in inflammatory status.

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PMID: 

J Ethnopharmacol. 2020 Apr 18 ;258:112874. Epub 2020 Apr 18. PMID: 32311485

Abstract Title: 

Anti-osteoporotic effects of Salvia miltiorrhiza Bunge EtOH extract both in ovariectomized and naturally menopausal mouse models.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza is a traditional oriental medicine widely used for preventing and treating disorders of the liver, menstrual, and blood circulation systems. Osteoporosis, loss of bone with age and/or estrogen deficiency, is an important causal factor of fracture. S. miltiorrhiza extract has been used to alleviate dysmenorrhea and painful osteoarthritis.AIM OF THE STUDY: This study was performed to investigate the anti-osteoporosis activity of the Salvia miltiorrhiza ethanol extract (SME) in osteoporosis-prone conditions: ovariectomized (OVX) and naturally menopaused (NM) ICR mice.MATERIALS AND METHODS: Anti-osteoporotic potentials of SME (50-200 mg/kg) were evaluated based on bone mineral density using microCT analysis, biochemical parameters, and changes in the gene expressions involved in bone resorption.RESULTS: SME ameliorated the loss of trabecular bone both in OVX and NM mice. SME was effective in correcting aberrant levels of RANKL, osteocalcin, and BALP, which are critically involved in bone resorption. In addition, SME suppressed the expression of TRAF6 and NFATc1, which play a role in osteoclast differentiation.CONCLUSIONS: SME suppressed the loss of trabecular bone via suppressing bone resorption and osteoclast differentiation both in OVX and NM mice. SME is likely to be developed as a therapeutic agent for osteoporosis.

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PMID: 

Nutrients. 2020 Apr 27 ;12(5). Epub 2020 Apr 27. PMID: 32349456

Abstract Title: 

Anti-Obesity Effects of Tanshinone I fromBunge in Mice Fed a High-Fat Diet through Inhibition of Early Adipogenesis.

Abstract: 

Tanshinone I (Tan I) is a diterpenoid isolated fromBunge and exhibits antitumor effects in several cancers. However, the anti-obesity properties of Tan I remain unexplored. Here, we evaluated the anti-obesity effects of Tan I in high-fat-diet (HFD)-induced obese mice and investigated the underlying molecular mechanisms in 3T3-L1 cells. HFD-induced obese mice were orally administrated Tan I for eight weeks, and body weight, weight gain, hematoxylin and eosin staining and serum biological parameters were examined. The adipogenesis of 3T3-L1 preadipocytes was assessed using Oil Red O staining and measurement of intracellular triglyceride (TG) levels, and mitotic clonal expansion (MCE) and its related signal molecules were analyzed during early adipogenesis of 3T3-L1 cells. The administration of Tan I significantly reduced body weight, weight gain, and white adipocyte size, and improved obesity-induced serum levels of glucose, free fatty acid, total TG, and total cholesterol in vivo in HFD-induced obese mice. Furthermore, Tan I-administered mice demonstrated improvement of glucose metabolism and insulin sensitivity. Treatment with Tan I inhibited the adipogenesis of 3T3-L1 preadipocytes in vitro, with this inhibition mainly occurring at an early phase of adipogenesis through the attenuation of MCE via cell cycle arrest at the G1/S phase transition. Tan I inhibited the phosphorylation of p38, extracellular signal-regulated kinase (ERK), and Akt during the process of MCE, while it stimulated the phosphorylation of AMP-activated protein kinase. Furthermore, Tan I repressed the expression of CCAAT-enhancer-binding proteinβ (), histone H3K9 demethylase, and subsequently cell cycle genes. Moreover, Tan I regulated the expression of early adipogenic transcription factors including GATAs and Kruppel-like factor family factors. These results indicate that Tan I prevents HFD-induced obesity via the inhibition of early adipogenesis, and thus improves glucose metabolism and insulin sensitivity. This suggests that Tan I possesses therapeutic potential for the treatment of obesity and obesity-related diseases.

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PMID: 

Emerg Microbes Infect. 2020 May 13:1-37. Epub 2020 May 13. PMID: 32397909

Abstract Title: 

Rosmarinic Acid Exhibits Broad Anti-Enterovirus A71 Activity by Inhibiting the Interaction between the Five-Fold Axis of Capsid VP1 and Cognate Sulfated Receptors.

Abstract: 

Enterovirus A71 (EV-A71), a positive-stranded RNA virus of the Picornaviridae family, may cause neurological complications or fatality in children. We examined specific factors responsible for this virulence using a chemical genetics approach. Known compounds from an anti-EV-A71 herbal medicine, Salvia miltiorrhiza (Danshen), were screened for anti-EV-A71. We identified a natural product, rosmarinic acid (RA), as a potential inhibitor of EV-A71 by cell-based antiviral assay and in vivo mouse model. Results also show that RA may affect the early stage of viral infection and may target viral particles directly, thereby interfering with virus-P-selectin glycoprotein ligand-1 (PSGL1) and virus-heparan sulfate interactions without abolishing the interaction between the virus and scavenger receptor B2 (SCARB2). Sequencing of the plaque-purified RA-resistant viruses revealed a N104 K mutation in the five-fold axis of the structural protein VP1, which contains positively charged amino acids reportedly associated with virus-PSGL1 and virus-heparan sulfate interactions via electrostatic attraction. The plasmid-derived recombinant virus harbouring this mutation was confirmed tobe refractory to RA inhibition. Receptor pull-down showed that this non-positively charged VP1-N104 is critical for virus binding to heparan sulfate. As the VP1-N104 residue is conserved among different EV-A71 strains, RA may be useful for inhibiting EV-A71 infection, even for emergent virus variants. Our study provides insight into the molecular mechanism of virus-host interactions and identifies a promising new class of inhibitors based on its antiviral activity and broad spectrum effects against a range of EV-A71.

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PMID: 

J Med Food. 2020 May 5. Epub 2020 May 5. PMID: 32379993

Abstract Title: 

Chemical Characterization of Bioactive Components ofExtract and Its Protective Effect on Dextran Sulfate Sodium-Induced Intestinal Bowel Disease in a Mouse Model.

Abstract: 

is a well-known medicinal plant used in folk remedy that alleviates various disorders, including inflammation, gastritis, and diarrhea. The objective of this investigation was to identify and quantify the phenolic components ofmethanolic extract (RCME) and to determine its protective action with dextran sulfate sodium (DSS)-generated mice colitis model. RCME chemical analysis was done using Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry, and experimental animals received RCME at different doses before colitis induction by oral DSS administration during 7 days. Another group received sulfasalazine as a positive control. Colitis damages and RCME benefits were assessed using histopathological and biochemical changes and improvements. Many phenolic compounds have been identified. In addition, the DSS intoxication induced an alteration of colonic epithelium associated with an oxidative stress state. DSS administration led to an increase or decrease of intracellular mediators such as free iron and ionizable calcium. RCME consumption effectively protected against colonic histological/biochemical alterations induced by DSS intoxication providing support for the traditional use of this plant.

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