PMID: 

In Vivo. 2020 May-Jun;34(3):1077-1084. PMID: 32354895

Abstract Title: 

Wogonin Influences Osteosarcoma Stem Cell Stemness Through ROS-dependent Signaling.

Abstract: 

: Backgorund/Aim: Wogonin, a flavonoid-like compound extracted from the root of Scutellaria baicalensis Georgi, has been shown to have anticancer effects against cancer cells. Osteosarcoma is the most malignant type of bone cancer and can appear in any bone, with a high propensity for relapse and metastasis. The present study aimed to assess the anticancer effects of wogonin on osteosarcoma stem cells.MATERIALS AND METHODS: The cytotoxic effects of wogonin on CD133Cal72 osteosarcoma stem cells were assessed through in vitro experiments by MTT assay, transwell assay, sphere-formation assay, flow cytometry, immunocytochemistry and western blotting.RESULTS: Wogonin suppressed stem cell characteristics and the expression of stem cell-related genes by regulating reactive oxygen species (ROS) levels and ROS-related signaling of CD133Cal72 cells, effects which were reversed by ROS scavenger N-acetylcysteine.CONCLUSION: Wogonin may be a promising candidate for successful clinical management of osteosarcoma by regulating ROS-related mechanisms and stem cell-related genes.

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PMID: 

Food Funct. 2020 Mar 1 ;11(3):2094-2106. Epub 2020 Mar 4. PMID: 32129352

Abstract Title: 

Rosmarinic acid alleviates ethanol-induced lipid accumulation by repressing fatty acid biosynthesis.

Abstract: 

Recent studies have demonstrated that rosmarinic acid is a valuable natural product for treatment of alcoholic liver disease. However, the mechanisms whereby rosmarinic acid improves alcoholic liver disease remain unclear. Here we performed experiments using a non-transformed mouse hepatocyte cell line (AML12). Oil-red O staining demonstrated that rosmarinic acid reduced ethanol-induced lipid accumulation. It was shown that rosmarinic acid prevented ethanol-induced elevation of the malondialdehyde level. We also found that rosmarinic acid inhibited ethanol-induced mRNA expression of tumor necrosis factor-α and interleukin 6. Metabolomics analysis revealed that rosmarinic acid ameliorated ethanol-induced fatty acid biosynthesis in the cytoplasm. In addition, palmitic acid was a candidate biomarker in cells exposed to ethanol or ethanol plus rosmarinic acid. Rosmarinic acid prevented the ethanol-induced increase in sorbitol that is a component of the polyol pathway. Moreover, we confirmed that rosmarinic acid attenuated ethanol-induced mRNA expression of fatty acid synthase, probably by modulating the AMPK/SREBP-1c pathway. Furthermore, rosmarinic acid prevented the ethanol-induced decrease ineight metabolites that are involved in mitochondrial metabolism, including glycine and succinic acid which are the components of carnitine synthesis. These results provide a crucial insight into the molecular mechanism of rosmarinic acid in alleviating ethanol-induced injury.

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PMID: 

Front Pharmacol. 2020 ;11:153. Epub 2020 Feb 28. PMID: 32184728

Abstract Title: 

A Review of the Anti-Inflammatory Effects of Rosmarinic Acid on Inflammatory Diseases.

Abstract: 

Inflammatory diseases are caused by abnormal immune responses and are characterized by an imbalance of inflammatory mediators and cells. In recent years, the anti-inflammatory activity of natural products has attracted wide attention. Rosmarinic acid (RosA) is a water-soluble phenolic compound that is an ester of caffeic acid and 3, 4-dihydroxyphenyl lactic acid. It is discovered in many plants, like those of the Boraginaceae and Lamiaceae families. RosA has a wide range of pharmacological effects, including anti-oxidative, anti-apoptotic, anti-tumorigenic, and anti-inflammatory effects. The anti-inflammatory effects of RosA have been revealed throughandstudies of various inflammatory diseases like arthritis, colitis, and atopic dermatitis. This article mainly describes the preclinical research of RosA on inflammatory diseases and depicts a small amount of clinical research data. The purpose of this review is to discuss the anti-inflammatory effects of RosA in inflammatory diseases and its underlying mechanism.

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PMID: 

Interdiscip Toxicol. 2019 Oct ;12(2):98-110. Epub 2020 Feb 20. PMID: 32206031

Abstract Title: 

Nephroprotective effect of green tea, rosmarinic acid and rosemary on N-diethylnitrosamine initiated and ferric nitrilotriacetate promoted acute renal toxicity in Wistar rats.

Abstract: 

The present study was designed to investigate the chemoprotective effect of green tea extract (GTE), rosmarinic acid (RA) and rosemary extract (RE) against diethylnitrosamine (DEN) initiated and ferric nitrilotriacetate (Fe-NTA) promoted nephrotoxicity in rats. Forty male rats were categorized into five: Group I included healthy rats, group II received DEN+Fe-NTA, group III received 200 mg/kg b.wt. of RE+DEN+Fe-NTA, group IV received 1 g/kg b.wt. of GTE+DEN+Fe-NTA and group V received 50 mg/kg b.wt. of RA+DEN+Fe-NTA. RE, GTE, RA were given orally for 14 days before single intraperitoneal administration of DEN (160 mg/kg) till the end of the experiment. Eighteen days after DEN, a single intraperitoneal dose of Fe-NTA (5 mg Fe/kg) was administrated to rats to promote nephrotoxicity. The biochemical parameters were analyzed in serum at time intervals while the malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) were assessed in both serum and renal tissues. Kidney from each group was histopathologically examined at time intervals. The administration of Fe-NTA after DEN dose to albino rats resulted in acute nephrotoxicity which was characterized by a highly significant elevation of serum urea, creatinine, uric acid (=0.000), serum and renal MDA and TNF-α (=0.000) with vacuolation of epithelial lining renal tubules. The administration of RE, GTE and RA prior to DEN+Fe-NTA treatment significantly ameliorated the observed increased levels of the above mentioned parameters. GTE, RA&RE exerted a protective effect against renal toxicity with GTE showing a more pronounced effect on renal function parameters while RA showed the best antioxidant impact.

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PMID: 

Toxicol Appl Pharmacol. 2020 Apr 19 ;397:115014. Epub 2020 Apr 19. PMID: 32320792

Abstract Title: 

Rosmarinic acid exerts a neuroprotective effect on spinal cord injury by suppressing oxidative stress and inflammation via modulating the Nrf2/HO-1 and TLR4/NF-κB pathways.

Abstract: 

Spinal cord injury (SCI) is a severe central nervous system injury for which few efficacious drugs are available. Rosmarinic acid (RA), a water-soluble polyphenolic phytochemical, has antioxidant, anti-inflammatory, and anti-apoptotic properties. However, the effect of RA on SCI is unclear. We investigated the therapeutic effect and underlying mechanism of RA on SCI. Using a rat model of SCI, we showed that RA improved locomotor recovery after SCI and significantly mitigated neurological deficit, increased neuronal preservation, and reduced apoptosis. Also, RA inhibited activation of microglia and the release of TNF-α, IL-6, and IL-1β and MDA. Moreover, proteomics analyses identified the Nrf2 and NF-κB pathways as targets of RA. Pretreatment with RA increased levels of Nrf2 and HO-1 and reduced those of TLR4 and MyD88 as well as phosphorylation of IκB and subsequent nuclear translocation of NF-κB-p65. Using HO- and LPS-induced PC12 cells, we found that RA ameliorated the HO-induced decrease in viability and increase in apoptosis and oxidative injury by activating the Nrf2/HO-1 pathway. Also, LPS-induced cytotoxicity and increased apoptosis and inflammatory injury in PC-12 cells were mitigated by RA by inhibiting the TLR4/NF-κB pathway. The Nrf2 inhibitor ML385 weakened the effect of RA on oxidant stress, inflammation and apoptosis in SCI rats, and significantly increased the nuclear translocation of NF-κB. Therefore, the neuroprotective effect on SCI of RA may be due to its antioxidant and anti-inflammatory properties, which are mediated by modulation of the Nrf2/HO-1 and TLR4/NF-κB pathways. Moreover, RA activated Nrf2/HO-1, which amplified its inhibition of the NF-κB pathway.

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Research shows that the value of optimal vitamin D levels in the body cannot be emphasized enough, especially among pregnant women

PMID: 

Naunyn Schmiedebergs Arch Pharmacol. 2020 04 ;393(4):581-589. Epub 2019 Nov 15. PMID: 31729545

Abstract Title: 

Carvacrol suppresses learning and memory dysfunction and hippocampal damages caused by chronic cerebral hypoperfusion.

Abstract: 

Chronic cerebral hypoperfusion (CCH) is a common phenomenon in many neurological diseases such as vascular dementia and Alzheimer's disease. Several drugs have been investigated to prevent and treat the CCH. The carvacrol (CAR) has been shown to have beneficial effects on various neurodegenerative and neuropsychiatric disorders. Accordingly, the present study was designed to evaluate the effect of CAR on neuronal damages in hippocampus in a well-defined model for CCH. Forty-eight male Wistar rats were equally divided into four groups of sham (A), CCH (B), CCH+ CAR 25, and 50 mg/kg/daily (C and D). The animals were subjected to permanent bilateral occlusion of the carotid arteries (2-vessel occlusion, 2VO) to induce CCH model. Cognitive function was evaluated by Morris water maze test. Morphological changes of hippocampus were assessed using Nissl staining. Free radical scavenging activity was measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Moreover, catalase (CAT) and superoxide dismutase (SOD) activities and lipid peroxidation levels were measured using biochemical analysis. CAR significantly improved the spatial learning and memory deficits assessed using the Morris water maze test. CAR also significantly attenuated neuronal necrosis as well as malondialdehyde (MDA) and elevated the levels of SOD and CAT activity in the hippocampus. The results indicate that CAR produces significant neuroprotective effects on neuronal damages induced by CCH. Protective effect of CAR may be mediated by antioxidative effect of this drug.

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PMID: 

Food Sci Nutr. 2019 Nov ;7(11):3581-3588. Epub 2019 Sep 10. PMID: 31763008

Abstract Title: 

Cardioprotective effects of curcumin and carvacrol in doxorubicin-treated rats: Stereological study.

Abstract: 

Doxorubicin (DOX) is a cardiotoxic drug. To reduce the harmful effects of DOX, two plant-derived components, including curcumin (CUR) and carvacrol (CAR), were considered. This study aimed to assess the protective effects of CUR and CAR on DOX-induced cardiotoxicity using physiological and stereological evaluations. Male rats were randomly allocated to six groups. Group's I-VI received phosphate-buffered saline (PBS), CUR (100 mg kg day), CAR (50 mg kg day), DOX (4 mg kg week), DOX-CUR, and DOX-CAR, respectively. On day 24, plasma troponin I and ECG were analyzed and the left ventricle underwent stereological assessment. The results showed a fivefold increase in troponin I in the DOX-treated animals compared to the PBS ones. Additionally, heart rate and QRS amplitude, respectively, reduced by 18% and 31% and QT interval and QRS duration, respectively, increased by 41% and 24% in the DOX group in comparison with the PBS rats ( 

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PMID: 

Pharmaceutics. 2019 Nov 13 ;11(11). Epub 2019 Nov 13. PMID: 31766227

Abstract Title: 

Enhancement in Site-Specific Delivery of Carvacrol against Methicillin ResistantInduced Skin Infections Using Enzyme Responsive Nanoparticles: A Proof of Concept Study.

Abstract: 

Methicillin resistant(MRSA) induced skin infections have become a challenging problem due to the escalating antibiotic resistance. Carvacrol (CAR) has been reported to be effective against MRSA. However, due to its characteristics, CAR exhibits low skin retention. In this study, CAR was formulated into site-specific nanoparticle (NPs) delivery system using poly(ε-caprolactone) (PCL), following incorporation into a hydrogel matrix to facilitate dermal delivery. The release study exhibited significantly higher release of CAR from PCL NPs in the presence of bacterial lipase, highlighting its potential for differential delivery. Moreover, encapsulation of CARin PCL NPs resulted in a two-fold increase in its anti-MRSA activity. Dermatokinetic studies revealed that the NPs loaded hydrogel was able to enhance skin retention of CAR after 24 h (83.29 ± 3.15%), compared to free CAR-loaded hydrogel (0.85 ± 0.14%). Importantly, this novel approach exhibitedeffective antimicrobial activity in an ex-vivo skin infection model. Hence, these findings have proven the concept that the loading of CAR into a responsive NPs system can lead to sustained antimicrobial effect at the desired site, and may provide a novel effective approach for treatment of MRSA induced skin infections. However, further studies must be conducted to investigate in-vivo efficacy of the developed system in an appropriate infection model.

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PMID: 

Neurotox Res. 2020 Apr ;37(4):965-976. Epub 2019 Dec 6. PMID: 31811590

Abstract Title: 

Protective Effects of Carvacrol on Brain Tissue Inflammation and Oxidative Stress as well as Learning and Memory in Lipopolysaccharide-Challenged Rats.

Abstract: 

Inflammation can cause memory impairment. In the present study, the effect of carvacrol on brain tissue inflammation and oxidative stress as well as learning and memory in lipopolysaccharide (LPS)-challenged rats was evaluated. The animals were grouped and treated: (1) control which received vehicle instead of LPS and carvacrol, (2) LPS (1 mg/kg; i.p. 120 min before behavioral tests), and (3-5) in these groups, 25, 50, or 100 mg/kg of carvacrol (i.p.) was administered 30 min prior to LPS. In a Morris water maze test, compared to LPS group, administration of all three doses of carvacrol shortened the elapsed time and the traveleddistance to find the platform, while it prolonged the traveled time in the target area. In a passive avoidance test, administration of all 25, 50, and 100 mg/kg carvacrol significantly increased the latency at the 3 h, 24 h, 48 h, and 72 h after the shock compared to the LPS group. Interleukin(IL)-6, malondialdehyde (MDA), and NO (nitric oxide) metabolites were increased in the brain by LPS injection, while thiol, superoxide dismutase (SOD), and catalase (CAT) were decreased. Pretreatment with carvacrol reduced IL-6, NO metabolites, and MDA, while it improved thiol content, CAT, and SOD.The results indicated that carvacrol protected from learning and memory impairment and the brain tissue inflammation and oxidative stress in LPS-challenged rats.

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