Rosmarinus Officinalis (Rosemary): A Novel Therapeutic Agent for Antioxidant, Antimicrobial, Anticancer, Antidiabetic, Antidepressant, Neuroprotective, Anti-Inflammatory, and Anti-Obesity Treatment

Cite this article: Rafie H, Soheila H, Grant E. Rosmarinus Officinalis (Rosemary): A Novel Therapeutic Agent for Antioxidant, Antimicrobial, Anticancer, Antidiabetic, Antidepressant, Neuroprotective, Anti-Inflammatory, and Anti-Obesity Treatment. Biomed J Sci&Tech Res1(4)2017. BJSTR.MS.ID.000371. DOI: 10.26717/BJSTR.2017.01.000371 ISSN: 2574-1241 DOI: 10.26717/BJSTR.2017.01.000371 Rafie Hamidpour. Biomed J Sci & Tech Res


Introduction
Rosmarinus officinalis, commonly known as rosemary, is an evergreen perennial shrub belonging to the Lamiaceae family [1]. Native to the Mediterranean region, rosemary is now cultivated around the world due to its use as a natural food preservative and flavoring agent [2]. Rosemary has also been used as a source of traditional medicine for centuries. Its applications have ranged from memory enhancement to the treatment of gastrointestinal diseases [3,4]. The secret behind the preservative and therapeutic abilities of rosemary lies in its essential oil and extract. While the chemical composition of these secondary metabolites varies considerably depending on ecological conditions, all rosemary essential oils and extracts contain biologically active compounds that make them unique [5]. For example, phenolic compounds such as carnosic acid, carnosol, and rosemarinic acid are responsible for the strong antioxidant activity of rosemary essential oil and extract [6]. This significant antioxidant activity not only makes rosemary an effective food preservative, but it also accounts for nearly all of rosemary's other therapeutic abilities, including its anticancer and anti diabetic mechanisms [7]. It is therefore the strong antioxidant compounds in its essential oil and extract that is making R. officinalis a plant of great interest in today's food and medical industries.
Rosmarinus officinalis has been used as a food preservative and flavoring agent for centuries, but only recently have its preservative mechanisms been investigated. Recent studies have displayed rosemary extracts' strong antibacterial, antifungal, and antioxidant activity, all of which combine to make the plant a very effective inhibitor of food pathogens [7-10]. As the public becomes more suspicious of artificial food additives, the demand for safer and more natural preservatives is growing steadily. With few side effects, rosemary has been identified as a natural preservative that could potentially replace artificial additives [10]. Perhaps even more significant than the preservative ability of R. officinalis is its therapeutic potential. Rosemary has been used as a source of traditional medicine since ancient times, but studies have only recently begun to realize its potential contributions to modern medicine.
Remarkably, Rosmarinus officinalis has displayed hepatoprotective, antispasmodic, anticarcinogenic, antitumorigenic, antimicrobial, anti-inflammatory, and antioxidant properties [7]. It has also shown antidiabetic and neuroprotective activities, among others [11]. These biological properties have made rosemary a potential new therapeutic agent in the treatment of many diseases. The purpose of this research article is to review the clinical studies that have demonstrated the preservative and therapeutic potential of Rosmarinus officinalis through the examination of the antioxidant, antimicrobial, anticancer, anti diabetic, antidepressant, neuro protective, anti-inflammatory, and anti-obesity properties of the plant's essential oil and extracts.

Antioxidant Activity
The antioxidant activity of Rosmarinus officinalis is welldocumented in the literature reviewed for this project. Indeed, no other biological activity of rosemary was studied more than its antioxidant property. This heightened attention is understandable. Unlike most of its biological activities, Rosemary's antioxidant activity is directly attributable to chemical compounds in the plant's essential oils and extracts. While synergistic mechanisms between many oil components likely contribute to the antioxidant activity, phenolic diterpenes such as carnosic acid, carnosol, and rosemarinic acid have been identified as the strongest antioxidants present in rosemary essential oil [6,12,13].
Rosmarinus Officinalis exerts its antioxidant effect through several metabolic pathways. For example, rosemary essential oil and extract have been shown to destroy and prevent free radicals [14,15]. Rosemary is also capable of preventing lipid peroxidation, a destructive process that is caused by oxidative stress [7,16]. In addition to reducing the amount of reactive species in the body, rosemary has been found to increase the activity of antioxidant enzymes [17]. All these effects augment the body's defense against harmful reactive species and oxidative damage. Oxidative stress contributes to the development of many diseases. A lack of antioxidant defenses and the resulting oxidative damage have been shown to cause both diabetes and cancer [18,19]. By limiting oxidative stress in the body, rosemary helps prevent diseases such as these that depend on the accumulation of free radicals and other reactive species. Therefore, the strong antioxidant activity of R. officinalis is vital to its therapeutic potential. Indeed, its antioxidant activity is fundamental to nearly all of rosemary's other therapeutic applications [7].

Antimicrobial Activity
Rosmarinus Officinalis has demonstrated potent antibacterial and antifungal activities in multiple studies. Like its antioxidant activity, the antimicrobial activity of rosemary depends on the chemical composition of its essential oil, which can vary greatly depending on location, climate, and time of harvest. The anti microbial activity of oil is also determined by the interactions between its components [5]. Rosemary has been shown to inhibit the growth of bacteria such as Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus [9, 20,21]. The significance of rosemary's antibacterial effect does not end there, however. According to one study, rosemary has the potential to inhibit the drug resistance of some bacteria by overcoming and reducing the impermeability of these bacteria's membranes [20]. This represents an innovative strategy for containing and eliminating resistant strains of bacteria. Rosemary essential oil can also increase the susceptibility of certain bacteria to standard antibiotics [21]. This impressive antibacterial activity makes R. officinalis a strong defense against common food pathogens and a promising new preservative that could replace artificial additives [10].
In addition to its antibacterial properties, Rosmarinus officinalis has several antifungal mechanisms. The plant's essential oil has been shown to inhibit the adhesion of Candida albicans by denaturing cellular structures and altering membrane permeability [22]. According to one study, rosemary can even prevent the development of highly resistant fungal bio-films. By coating nano particles with rosemary essential oil, a nano bio system was produced that significantly inhibited the adherence and biofilm development of Candida fungal strains [23]. Both these new strategies are necessary alternatives to traditional medicine in the treatment against drug-resistant fungi. The ability to inhibit the growth and aflatoxin production of many fungi contributes to rosemary's potential as an effective food preservative [24].

Anticancer Activity
Many studies have reported on the anticancer mechanisms of Rosmarinus officinalis. Rosemary has displayed significant anti proliferative activities against several human cancer cell lines. Major compounds in the plant's extract, such as carnosic acid, carnosol, and rosemarinic acid, have been shown to induce apoptosis within these cancer cells, possibly through the production of nitric oxide [19,[25][26][27]. Carnosic acid appears to be the strongest promoter of apoptosis [19,27]. Rosemary extract also has intriguing antitumorigenic activity. In one study, the extract was found to strongly inhibit skin tumorigenesis in mice by preventing carcinogens from binding to epidermal DNA [28]. This anti carcinogenic effect is caused by the extract's antioxidant activity [7]. These anti proliferative and anti tumorigenic activities of R. officinalis can possibly be utilized in future cancer treatments and warrant further investigation.

Antidiabetic Activity
Diabetes mellitus is a growing worldwide disorder. By 2025, an estimated 300 million people will be diabetic, and global costs of treating the disease could reach US $1 trillion annually [18]. The development of diabetes is often fostered by high oxidative stress; pancreatic β-cells are especially vulnerable to reactive oxygen species, leading to decreased insulin secretion and higher blood glucose levels [18]. This information has prompted new diabetes treatments to focus on natural antioxidants, particularly those found in plants. Not surprisingly, multiple studies have identified Rosmarinus officinalis as a promising anti diabetic agent. Rosemary's antioxidant properties execute several anti diabetic and hypoglycemic mechanisms. In one study, rosemary extract lowered blood glucose levels in normoglycemic, hyperglycemic, and diabetic rabbits. By inhibiting lipid peroxidation and activating antioxidant enzymes, the extract also promoted insulin secretion [18]. Rosemary was also found to alleviate delayed wound healing, a serious complication of diabetes [29]. These anti diabetic activities are attributable to the body's improved antioxidant status after administration of rosemary [30].

Antidepressant Activity
The potential use of Rosmarinus officinalis as an antidepressant was the focus of many research articles reviewed for this project. The majorities of these studies involved two tests that are used to model antidepressant like effects in mice-the Tail Suspension Test (TST) and Forced Swimming Test (FST). The administration of rosemary continuously decreased the immobility time of mice in both the TST and the FST, indicating an antidepressantlike effect [31][32][33][34]. Rosemary's antidepressant potential was further bolstered when it was found to decrease exploratory and anhedonic-like behavior in bulbectomized mice [35]. There is much evidence that the antidepressant activity of R. officinalis depends on interactions with the monoaminergic system. Rosemary is believed to enhance dopaminergic, serotonergic, noradrenergic, and cholinergic functions within the brain, possibly explaining its antidepressant effects [31][32][33]. Rosemary has also been found to increase the concentration of neurotransmitters in the brains of mice [33]. Several compounds in rosemary extract and essential oil are responsible for its antidepressant activity, including carnosol, betulinic acid, ursolic acid, and polyphenols [31,33,34].

Neuroprotective Activity
Remarkably, Rosmarinus officinalis has demonstrated significant neuroprotective effects against neurodegenerative diseases such as Alzheimer's disease and dementia. Rosemary has displayed inhibitory activities against the two enzymes in the brain responsible for the breakdown of Acetylcholine-Cholinesterase (AChE) and Butyryl Cholinesterase (BChE). These anti-AChE and anti-BChE activities are likely caused by rosemarinic acid and terpene compounds in the plant's essential oil [4,36]. By increasing total choline levels in the brain, rosemary could attenuate not just Alzheimer's disease, but also memory loss, anxiety, and depression [37,38]. Two more studies highlight the neuroprotective ability of R. officinalis. In the first, polyphenols present in rosemary extract were found to inhibit stress proteins, which play a role in the neurodegenerative process [39]. The second study concluded that rosemary promotes the production of nerve growth factor (NGF), a protein vital to the growth and maintenance of nerve tissue. Increased NGF levels can help alleviate Alzheimer's disease, dementia, and other neurodegenerative diseases [40]. Both these studies clearly demonstrate rosemary's growing potential as a neuro protective agent.

Anti-Inflammatory Activity
Rosmarinus officinalis displayed potent anti-inflammatory mechanisms in several of the reviewed studies. Rosemary essential oil and extract were found to significantly inhibit leukocyte migration in vivo [41]. This reduced the number of leukocytes (White Blood Cells) at the site of inflammation, resulting in an anti-inflammatory response [42,43]. Rosemary extract also inhibited other proinflammatory substances, such as nitric oxide and inflammationassociated genes [42][43][44]. While carnosol and carnosic acid appear to be particularly important, the anti-inflammatory activity of rosemary most likely depends on a synergistic mechanism between many of its components [41,42,44]. These studies suggest that the anti-inflammatory effect of R. officinalis is rather strong; in fact, the anti-inflammatory activities of pure carnosol and carnosic acid were found to be nine times higher than that of indomethacin, a common anti-inflammatory drug [42].

Anti-obesity Activity
While only three studies reported anti-obesity activities of Rosmarinus officinalis, their findings are very noteworthy. All three found rosemary to effectively limit weight gain, but each study identified a different mechanism to explain this response. In one study, extracted carnosic acid was found to suppress adipocyte differentiation. This inhibition of adipogenesis can promote sustainable weight loss [45]. In another study, rosemary extract prevented weight gain by limiting lipid absorption in the intestine. This was made possible through the inhibition of pancreatic lipase activity [46]. Finally, the third study found rosemary extract to inhibit lipid synthesis through the suppression of Diacylglycerol Acyltransferase (DGAT), the main enzyme responsible for the production of triglycerides [47]. The results of all three studies indicate that R. officinalishas great potential as an effective treatment against obesity and other metabolic disorders [45][46][47].

Discussion
Rosmarinus officinalis, an evergreen perennial shrub commonly known as rosemary, is garnering considerable attention from the food and medical industries due to its wide array of biological activities. Rosemary has been used as a source of traditional medicine for centuries, but its potential as a natural food preservative has only recently been investigated [4]. Studies have shown that the strong antioxidant and antimicrobial activities of the plant's extracts make rosemary an ideal replacement for more toxic artificial food additives [9,10]. As concern over these potentially harmful additives has grown, so has the demand for natural preservatives such as rosemary. While rosemary is beginning to be used as a preservative around the globe, more can be done to maximize the plant's potential. Additional research is needed to 4/6 identify the extracts and essential oils of rosemary that have the most potent preservative activities. Toxicity levels and potential side effects of rosemary must also be constantly monitored. Assuming it remains less toxic, R. officinalis should continue to replace artificial additives in many preservative applications, thereby reducing risk to consumers.
Rosmarinus officinalis has also displayed many intriguing therapeutic properties. Rosemary's antimicrobial, antidepressant, neuro protective, anti-inflammatory, and anti-obesity activities all have potential in the treatment against various diseases. However, it is the anticancer and anti diabetic mechanisms of rosemary that warrant the most attention. Oxidative stress has been shown to contribute to the progression of diabetes mellitus and many forms of cancer [15]. It is not surprising, then, that the strong antioxidant activity of rosemary extract and essential oil represents a promising new strategy in the treatment of both diseases. The plant's ability to promote insulin secretion in diabetic patients and induce apoptosis within cancer cells is particularly intriguing. While these initial results have been encouraging, more clinical studies are needed before rosemary can be regularly used in humans. If it continues to display such promising anti diabetic and anticancer activities with few side effects, R. officinalis could eventually provide an innovative treatment in the fight against these two serious diseases.

Conclusion
Rosmarinus officinalis (rosemary) has displayed exciting potential as both a natural food preservative and a therapeutic agent in the literature reviewed for this project. The low toxicity levels and strong antioxidant, antibacterial, and antifungal activities of the plant's extract make rosemary an effective food preservative with fewer side effects than artificial additives. The strong antioxidant compounds found in its extract and essential oil account for many of rosemary's biological activities, including its anti diabetic and anticancer mechanisms. Rosemary has also been found to alleviate depression, neurodegenerative diseases, inflammation, and obesity. While the initial results have been encouraging, additional research is needed to confirm the safety and efficacy of R. officinalis as a preservative and therapeutic agent (Figure 1-3).