Shin, Choi, Ryu, Lee, Kim, Choi, Chang, Lee, Jang, and Inn (2013) conducted a study testing the effectiveness of carnosic acid in treating human respiratory syncytial virus (hRSV).  At the time of the study, there was no vaccine and no effective study.  They tested three herbs, the other two were not very effective against hRSV so they just used rosemary in this study.  They extracted carnosic acid, rosmarinic acid, and butalinic acid but focused the study on carnosic acid.  They also determined carnosol has no effect on hRSV.  The authors also evaluated cytotoxicity and determined there was minimal cell degradation due to toxicity. 

The results using carnosic acid against hRSV were effective.  After two days at a dose of 20 micrograms per milliliter, the virus had reduced by 26-fold.  At a dose of 50 midcr50 micrograms the number had risen to 1160-fold.  After four days at the 50 dose, there was no virus remaining. It was effective against both a and b type hRSV viruses.  However effective this was against hRSV, they tested it against the flu and had no effect suggesting it has a very specific way of working against some viruses.  Treatment 8 and 12 hours after infection were still effective at 70% and 50%.  

They also tested using pretreatment and the results suggested carnosic acid may inhibit hRSV infection.  While they still do not fully understand how it works, they think because it was ineffective against influenza A, it must attack the virus itself rather than protect the host cells.  For this same reason, they believe it does not attack the RNA of a virus.  The current thinking it is works against proteins which inhibits RNA synthesis.
 
Shin, H., Choi, M. Ryu, B., Lee, N., Kim, H., Choi, H., Chang, J., Lee, K. T., Jang, D. S., and Inn, K. (2013). Antiviral activity of carnosic acid against respiratory syncytial virus.  Virology Journal, 10:303.

Zhao, Lee, Ma, Huang, Sun, Li, Chen, and Niu (2012) studied the effects of carnosol, an antioxidant on estrogen receptors. This is an attempt to find a solution to postmenopausal cardiovascular symptoms that do not bear a cancer-causing risk such as hormone replacement therapy.

Estrogen receptor a played a bigger role in this study that estrogen receptor b but it was clear that carnosol was effective overall in this study.  Carnasol played a significant role in reducing induced oxidative stress in a vascoprotective way.  Meaning, it prevented cell death caused by oxidative stress.  It displayed phytoestrogenic activity in BAECs. 

The estrogen receptors have also demonstrated antioxidant properties, especially estrogen receptor a which inhibited some of the carnosol activity. This study showed carnosol used the estrogen receptor pathway to exert its antioxidative properties.  However, the binding ability is different due to the structure of the phytoestrogen cells.  When the cells were pretreated with carnosol 24 hours prior to induced oxidative stress, the cardiovascular cells were not damaged by the oxidative stress. 

The authors of the study say there are existing studies which indicate daily intake if carnasol in animals is well tolerated.
 
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Zhao, P., Lee, D. Y., Ma, Z., Huang, L., Sun, L., Li, Y., Chen, J., and Niu, J. (2012). The Antioxidant Effect of Carnosol in Bovine Aortic Endothelial Cells Is Mainly Mediated via Estrogen Receptor α Pathway. Biological Pharmacological Bulletin, 35(11):1947–1955

This constituent isn't really "new" but it was not listed in any of the books I used as sources so I do not have it defined in my constituent list nor is it listed in my rosemary herbarium yet.

Miyazawa, Sugie, and Shindo (2002) looked at the biotransformation of the constituent verbenone which is found is the essential oil of rosemary.  In the study they were able to determine it transforms into a metabolite called 10-hydroxyverbenone.  The authors conclude the study with indicating further studies were underway on this topic.

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Miyazawa, M., Sugie, A., and Shindo, M. (2002). Biotransformation of Verbenone by Human Liver Microsomes. Bioscience, Biotechnology and Biochemistry, 66(11): 2458-2460.

Vicente, Martin, Garcia-Risco, Fornari, and Reglero (2012) examined the extraction of rosemary’s antioxidant constituents using carbon dioxide and combing them with sunflower oil, linseed oil and grapeseed oil to determine if there was any effect on the antioxidant ability of the rosemary constituents. 

They determined if ethanol is not used with the carbon dioxide extraction process, the antioxidant ability is greatly reduced. No matter which method, with or without ethanol, the linseed oil had the most carnasol and carnosic acid, increasing as the dosage increased, The grapeseed oil had the least.

The interesting part the authors noted was the linseed oil without the rosemary was the most likely to oxidize. There was a direct relationship to the amount of PUFA (polyunsaturated fatty acids) to the likelihood of susceptibility of oxidation. 

The sunflower oil had the least PUFA and was in between the other two oils in terms of absorption of the rosemary constituents. Linseed oil had the most PUFA and absorbed the most. Grapeseed oil was the middle on PUFA but the last on absorption.

The authors are now wondering if the composition of the PUFA is the cause of oxidation.  Linseed oil was 43% linolenic acid (Omega-3) and 19% linoleic acid (Omega-6). Grapeseed oil had 68% linoleic acid, and Sunflower oil had 44% linoleic acid. They also are wondering if the position of the double bonds has an effect. Constituents which are a natural part of the original oils may also play a role.
 
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Vicente, G., Martin, D., Garcia-Risco, M. R., Fornari, T., and Reglero, G. (2012). Supercritical Carbon Dioxide Extraction of Antioxidants from Rosemary (Rosmarinus officinalis) Leaves for Use in Edible Vegetable Oils. Journal of Oleo Science, 61(12):689-697.

Kayashima and Matsubara (2012) studies carnosic acid and carnosol themselves and determined carnosic acid is neuroprotective and is dose dependent where carnosol is not dose defendant with the same activity.  In mice, they fed these constituents then looked at the inside of the aorta of each mouse to determine the effectiveness.  The images in this study speak volumes though they only show the comparison between carnosic acid and the control, not one for carnosol.  For carnosol, at a dose of 10 micrometers, microvessel growth was inhibited at 32% (these support the growth of tumors).  At a dose of 50, that percentage only went up to 37%.  The authors felt the carnosic acid was converting a small amount to carnosol to support this activity. The effect of carnosol and carnosic acid on endothelial cells were different which may have resulted on the carnosol being weaker. Carnosic acid seems to work by activating the Keap1/Nrf2 transcription pathway to express antioxidant enzymes and protect against oxidative stress. They end their study mentioning there are studies underway to determine the exact pathways that these 2 constituents use to be effective in protecting these cells.

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Kayashima, Y., and Matsubara, K. (2012). Antiangiogenic Effects of Carnosic Acid and Carnosol, Neuroprotective Compounds in Rosemary Leaves. Bioscience, Biotechnology and Biochemistry, 76(1): 115-119. Doi: 10.1271/bbb.110584

Wada, Nagano, Kido, Ikeda, Kuroda, and Nakashima (2011) evaluated rosemary extract in both water and isopropanol to evaluate antioxidative effects using the thiobarbituric acid (TBA) method. 

The water extract was 65% oxidative and the isopropanol extract was 31%.  The control was 8% oxidative. This was indicated by the amount of rosemary extract in the blood plasma tested, which was taken from volunteers. 

They tested the extracts at different concentrations: 10, 20, 30, 40, and 50 milligrams per milliliter.  With each increase in concentration, there was in increase in antioxidative activity.  In each, the water extract was more than the other, with 50 being more than twice as effective.

Constituents were not determined using this method therefore it was not determined what was causing the effect.

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Wada, M., Nagano, M., Kido, H., Ikeda, R., Kuroda, N., and Nakashima, K. (2011). Suitability of TBA Method for the evaluation of the Oxidative Effect of Non-water-soluble and water-soluble Rosemary Extracts. Journal of Oleo Science 60(11): 579-584

While the picture above is of my rosemary bush and the title says this article is about cinnamon, I came across this article while researching rosemary and the plant was included in the study.  While it was effective, it was the LEAST effective of those studied with cinnamon being the most.  This was quite an interesting article.  I hope you enjoy the summary I wrote!

Taguchi, Takizawa, Ishibashi, Sagawa, Arai, Inoue, Yamaguchu, Abe, (2010) conducted a study to determine herbal effectiveness against candida albicans. Herbs tested were lemongrass, lemon balm, rosemary, roselle, spearmint, green tea, cinnamon (Cinnamomum cassia), and thyme.  Lemongrass, green tea and cinnamon were the strongest when tested against clove (which had a numbing effect in previous studies making some results difficult to read). Cinnamon was the strongest. 

All herbs were extracted using water at 90 degrees Celsius for 5 minutes. This methodology was to test the viability of a tea used medicinally. This extract was then diluted to determine what amount was needed for effectiveness. 

Of the herbs tested, rosemary performed the worst with having to use 25-50% of the extract to get a 50% kill ratio of the candida.  Spearmint was 12.5-25%. Lemon balm and thyme were 6.25-12.5%.  Lemon grass and green tea were less than 6.25% of the extract to achieve a 50% kill ratio.  Cinnamon was put directly in the mouth of the mice instead of in the water and it was 1-5% of the extract.  It took twice as much for each herb to achieve an 80% kill ratio except with cinnamon and clove which was the control. The clove numbers were 5-25% of the extract for both a 50% kill ratio and an 80% kill ratio. 

Since cinnamon doesn’t dissolve completely in water, they wanted to make sure the undissolved particles were included in the treatment, hence the variation. They did a symptom comparison between the control and cinnamon at different ratios.  Only the 100% cinnamon treatment had a significant result in comparison. 

There was about 200 milligrams of solid matter per milliliter in the cinnamon extract. In looking at cinnamon closer, the original extract had 19.5 milligrams per milliliter of cinnamaldehyde and 3.09 milligrams per milliliter of coumarin.  They put it in a centrifuge and tested the top layer (supernatant) and bottom layer (precipitate). The supernatant portion had 5.38 milligrams per milliliter of cinnamaldehyde and .99 milligrams of coumarin while precipitate portion was 3 or 4 times that for each.

In testing effectiveness, the supernatant needed 20-100% dilution while the precipitate was 256-1024%. The dry matter in the precipitate was ten times that of the supernatant.
 
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Taguchi, Y., Takizawa, T., Ishibashi, H., Sagawa, T., Arai, R., Inoue, S., Yamaguchu, H., Abe, S. (2010). Therapeutic Effects on Murine Oral Candidiasis by Oral Administration of Cassia (Cinnamomum cassia) Preparation.  Jpn. Med. Mycol. 51: 13-21.

Luo, Pan, Pan, Han, and Zhong (2010) investigated rosemary, echinacea, pine bark and propolis for their ability to protect DNA strands against breakage, tyrosine nitration and LDL oxidation. They started with 32 herbs used in Chinese medicine but these four were the only ones effective of those initially looked at. They also looked at rosmarinic acid (from rosemary) and chicoric acid (from echinacea) specifically to see if they protect against tyrosine nitration and LDL oxidation.

The rosemary extract had hesperidin, caffeic acid, rosmarinic acid (13%), and ferulic acid. The echinacea extract had chicoric acid (12%), chlorogenic acid, caffeic acid, and echinacea saponin. Echinacea’s scavenging activity was 76.6% while rosemary was 88.9%. Propolis was 95.8% and pine bark was 82%.  The rest are listed as 33% effective or less. 

Propolis was significant at 5-15 micrograms per milliliter. The other three were 10-15.  This is why these 4 were selected for this study. In all 32 herbs, there was a correlation with phenolic content to the percentage of scavenging.  However, rosemary and echinacea were lower than the proportion noted in the study.  The researcher noted they feel there was a special component in these two herbs. 

With induced tyrosine nitration, propolis was 98% effective with a 100 microgram/milliliter concentration. Pine bark was 93%, rosemary was 73% and echinacea was 43%.  Caffeic acid and chlorogenic acid were less effective than chicoric acid (echinacea).  In rosemary, only the rosmarinic acid seemed effective. Both the chicoric acid and rosemarinic acid were more effective than the extract when tested alone.

At a concentration of 50micrograms/milliliter, chicoric acid had a 82% effective rate while echinacea had a 35.3% rate at that concentration.  Likewise, rosmarinic acid was 69% to rosemary’s 54%. 

When looking at DNA damage and the potential to repair it, propolis was 70% effective while rosemary was 40% and echinacea was 35%.  In the LDL portion of the study, propolis and pine bark were superior but the authors mentioned rosemary does not work the same way as the others so the test may not have done it justice.  The pine bark worked better with lipids to be more effective.  Echinacea was the worst of the four tested.  Chicoric acid was more effective than echinacea.

They did mention that rosmarinic acid was acting more synergisticaly.  This means when isolating active ingredients, while the other herbs had one effective element, it is prudent with rosemary to determine what other elements provide that synergistic effect to be useful in medications. 

Potential drugs from these herbs may treat ailments such as Alzheimer’s and Parkinson’s disease as well as carcinogenesis. NOTE: The authors referred to rosmarinic acid as rosemary acid.

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Luo, Y., Pan, J., Pan, Y., Han, Z., and Zhong, R. (2010). Evaluation of the Protective Effects of Chinese Herbs Against Biomolecule Damage Induced by Peroxynitrite. Bioscience, Biotechnology and Biochemistry, 74(7): 1350-1354.

Gramza-Michalowska, Korczak, and Regula (2007) noted the current antioxidants used in butter can cause cancer and wanted to investigate potential natural sources for the same antioxidant activity.  They used summer and winter milk as the feed for the cows differs by season and may impact this process.  They noted the summer milk deteriorated faster than winter milk but both consumed oxygen at the same rate.

The natural antioxidants they tested were green tea and rosemary. In both samples (summer and winter), green tea was 300% over control and rosemary was 200% over control. They used a 95% extract for each herb.  The synthetics used for comparison were BHT and a-tocopherol. 

Green tea out-performed all of those tested against. Rosemary was superior to BHT in the summer sample but not the winter sample by a small margin.

In terms of lipid stability, the green tea was 270% better than control while rosemary lasted twice as long as that of the control.  A-tocopherol performed about the same as green tea while BHT was inferior to rosemary. The authors mentioned green tea performed the same way in other tests against a-tocopherol using sunflower oil and lard.
 
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Gramza-Michalowska, A., Korczak, J., and Regula, J. (2007). Use of plant extracts in summer and winter season butter oxidative stability improvement. Asia-Pacific Journal of Clinical Nutrition, 16 (Suppl 1):85-88.