The Role of Rosmarinic Acid on the Bioproduction of Gold Nanoparticles as Part of a Photothermal Approach for Breast Cancer Treatment

Breast cancer is a high-burden malignancy for society, whose impact boosts a continuous search for novel diagnostic and therapeutic tools. Among the recent therapeutic approaches, photothermal therapy (PTT), which causes tumor cell death by hyperthermia after being irradiated with a light source, represents a high-potential strategy. Furthermore, the effectiveness of PTT can be improved by combining near infrared (NIR) irradiation with gold nanoparticles (AuNPs) as photothermal enhancers. Herein, an alternative synthetic method using rosmarinic acid (RA) for synthesizing AuNPs is reported. The RA concentration was varied and its impact on the AuNPs physicochemical and optical features was assessed. Results showed that RA concentration plays an active role on AuNPs features, allowing the optimization of mean size and maximum absorbance peak. Moreover, the synthetic method explored here allowed us to obtain negatively charged AuNPs with sizes favoring the local particle accumulation at tumor site and maximum absorbance peaks within the NIR region. In addition, AuNPs were safe both in vitro and in vivo. In conclusion, the synthesized AuNPs present favorable properties to be applied as part of a PTT system combining AuNPs with a NIR laser for the treatment of breast cancer.

Differential action of pro-angiogenic and anti-angiogenic components of Danhong injection in ischemic vascular disease or tumor models

Objective We investigate the chemical basis and mechanism of angiogenesis regulation by a multicomponent Chinese medicine Danhong injection (DHI). Methods DHI was fractionated and screened for angiogenesis activities by in vitro tube formation and migration assays. The composition of DHI components was determined by UPLC. The effects of the main active monomers on angiogenesis-related gene and protein expression in endothelial cells were determined by qPCR and Western blotting analyses. Mouse hind limb ischemia and tumor implant models were used to verify the angiogenesis effects in vivo by Laser Doppler and bioluminescent imaging, respectively. Results Two distinct chemical components, one promoting (pro-angiogenic, PAC) and the other inhibiting (anti-angiogenic, AAC) angiogenesis, were identified in DHI. PAC enhanced angiogenesis and improved recovery of ischemic limb perfusion while AAC reduced Lewis lung carcinoma growth in vivo in VEGFR-2-Luc mice. Among the PAC or AAC monomers, caffeic acid and rosmarinic acid upregulated TSP1 expression and downregulated KDR and PECAM expression. Caffeic acid and rosmarinic acid significantly decreased while protocatechuic aldehyde increased CXCR4 expression, which are consistent with their differential effects on EC migration. Conclusions DHI is capable of bi-directional regulation of angiogenesis in disease-specific manner. The pro-angiogenesis activity of DHI promotes the repair of ischemic vascular injury, whereas the anti-angiogenesis activity inhibits tumor growth. The active pro- and anti-angiogenesis activities are composed of unique chemical combinations that differentially regulate angiogenesis-related gene networks.

New insights into the competition between antioxidant activities and pro-oxidant risks of rosmarinic acid

Direct and indirect antioxidant activities of rosmarinic acid (RA) based on HOO˙/CH3OO˙ radical scavenging and Fe(iii)/Fe(ii) ion chelation were theoretically studied using density functional theory at the M05-2X/6-311++G(2df,2p) level of theory.

Biochemical parameters and antioxidant property of three Salvia L. taxa endemic in Turkey

The aim of the present study was to determine and compare the fatty acids, lipid soluble vitamins, sterols, phenolics, and antioxidant capacities of three endemic Salvia L. taxa (S. euphratica var. Montbret & Aucher ex Bentham leiocalycina (Rech. Fil.) Hedge, S. euphratica var. Montbret & Aucher ex Bentham euphratica (Rech. Fil.) Hedge and S. pseudoeuphratica Rech.Fil.) and to evaluate these results systematically. The fatty acid compositions were determined by using gas chromatography, while the lipid soluble vitamins, sterols, and phenolics were determined by using HPLC. Also, the antioxidant capacities of three Salvia taxa were measured in vitro. Palmitic acid was found as major saturated fatty acid while oleic acid, linoleic acid, α-linolenic acid, and erucic acid were found as major unsaturated fatty acids in the present study. It was found that S. euphratica var. euphratica had lower palmitic acid (8.94 ± 0.71%), total saturated fatty acid (19.16 ± 0.15%), and higher unsaturated fatty acid content (82.08 ± 0.52%) than other studied taxa. Furthermore, it was shown that S. euphratica var. euphratica had different 18.3/18:2 (0.36) unsaturated/saturated fatty acid (4.28) ratios. However, this study demonstrated that Salvia taxa had low lipid soluble vitamins, sterol contents. On the other hand, it was shown that Salvia taxa had similar catechin (509.2 ± 4.21 µg/g and 552.2 ± 9.21 µg/g) and vanillic acid amounts (351.2 ± 2.17 µg/g and 396.8 ± 4.1 µg/g) in this study. And also, it was found that Salvia taxa had high rosmarinic acid content while S. euphratica var. leiocalycina had the highest rosmarinic acid content (1480 ± 7.57 µg/g). On the other hand, it was shown that the two ferulic acid contents of S. euphratica varieties were higher (1175 ±/5.21 µgmg-1740.2 ± 4.82 µg/mg) than the ferulic acid content of S. pseudoeuphratica of which was the lowest (19.2 ± 0.97 µg/mg). The present results suggested that the biochemical results guided the morphological studies, and Salvia taxa have a potent antioxidant capacity.

Rosmarinic acid production in cell suspension cultures of Ehretia asperula Zollinger & Moritz

Plant cell cultures provide an alternative means for producing secondary compounds in food, cosmetic and pharmaceutical industries. Ehretia asperula Zollinger & Moritzi is used as a traditional medicine for the treatment of liver detoxification, ulcers, tumors, inflammation and enhancing the body's resistance in Vietnam. The study was carried out to select suitable callus line for cell suspension cultures of E. asperula Zollinger & Moritzi and investigate the effects of inoculum size, rotation speed and naphthalene acetic acid (NAA) on the proliferation of cell suspension cultures. In addition, the influence of light intensity on the growth and rosmarinic acid (RA) biosynthesis of cell suspension was also surveyed. After 4 weeks of culture, the white to pale yellow friable callus expanded significantly with a fresh weight (FW) of 0.788 g and a high RA content of 2.062 mg/g FW. An appropriate medium for cell proliferation was the liquid B5 medium, which contained 30 g/l glucose, 0.1 mg/l benzyl adenine (BA) and 0.4 mg/l NAA. The results also demonstrated that a 1:20 ratio (w/v) inoculum size, darkness and rotation speed of 90 rpm were the optimal conditions for the proliferation and RA accumulation to 188.217 mg/l in 4 weeks of culture. These findings showed that E. asperula Zollinger & Moritzi cell suspension cultures could be a potential alternative approach for RA production in vitro.

Potential Inhibitors Identification of Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Angiotensin-Converting Enzyme 2 and Main Protease from Anatolian Traditional Plants

Background: The 2019 novel coronavirus disease (COVID-19) has caused a global health catastrophe by affecting the whole human population around the globe. Unfortunately, there is no specific medication or treatment for COVID-19 currently available. Objective: It’s extremely necessary to apply effective drug treatment in order to end the pandemic period and return daily life to normal. In terms of the urgency of treatment, rather than focusing on the discovery of novel compounds, it is critical to explore the effects of existing herbal agents with proven antiviral properties on the virus. Method: Molecular docking studies were carried out with three different methods, Glide extra precision (XP) docking, Induced Fit docking (IFD), and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA), to determine the potential effects of 58 phytochemicals in the content of Rosmarinus officinalis, Thymbra spicata, Satureja thymbra, and Stachys lavandulifolia plants -have antiviral and antibacterial effects- against Main Protease (Mpro) and Angiotensin Converting Enzyme 2 (ACE2) enzymes. Results: 7 compounds stand out among all molecules by showing very high binding affinities. According to our findings, the substances chlorogenic acid, rosmarinic acid, and rosmanol exhibit extremely significant binding affinities for both Mpro and ACE2 enzymes. Furthermore, it was discovered that carnosic acid and alpha-cadinol showed potential anti-Mpro activity, whereas caffeic acid and carvacrol had promising anti-ACE2 activity. Conclusion: Chlorogenic acid, rosmarinic acid, rosmanol, carnosic acid, alpha-cadinol, caffeic acid, and carvacrol compounds have been shown to be powerful anti-SARS-COV-2 agents in docking simulations against Mpro and ACE2 enzymes, as well as ADME investigations.