Cymbopogon Species; Ethnopharmacology, Phytochemistry and the Pharmacological Importance

Cymbopogon genus is a member of the family of Gramineae which are herbs known worldwide for their high essential oil content. They are widely distributed across all continents where they are used for various purposes. The commercial and medicinal uses of the various species of Cymbopogon are well documented. Ethnopharmacology evidence shows that they possess a wide array of properties that justifies their use for pest control, in cosmetics and as anti-inflammation agents. These plants may also hold promise as potent anti-tumor and chemopreventive drugs. The chemo-types from this genus have been used as biomarkers for their identification and classification. Pharmacological applications of Cymbopogon citratus are well exploited, though studies show that other species may also useful pharmaceutically. Hence this literature review intends to discuss these species and explore their potential economic importance.


Introduction
The presence of secondary metabolites in plants is characterized by their ability to provide defenses against biotic and abiotic stress [1]. The mechanism of defense varies from plant to plant, their environmental conditions and climatic variations. However, the presence of these metabolites in plant are usually in minimum amounts though several molecular techniques are available to either increase or decrease the quantity of a particular metabolite by blocking competitive pathways and enriching metabolites of choice [2]. Terpenes, alkaloids (N-containing compounds) and phenolics constitute the largest groups of secondary metabolites. The shikimic acid pathway is the basis of the biosynthesis of phenolics while the terpenes which are comprised of isoprene units arise from the mevalonate pathway [3]. Aspirin (1) from white willow, quinine (2) from the cinchona plant and artemisinin (3) from Artemisia annum are all plant secondary metabolites. The biological application of these metabolites as therapeutic agents for a broad spectrum of ailments and the microbial infections has been salutary in human history.
The genus Cymbopogon is widely distributed in the tropical and subtropical regions of Africa, Asia and America. Comprised of 144 species, this genus is famous for its high content of essential oils which have been used for cosmetics, pharmaceuticals, and perfumery applications [4]. Two main species, C. flexuosus and C. citratus (lemongrass) are commercially cultivated in the Democratic Republic of Congo (DRC), Madagascar, and the Comoros Island. However, the leading exporter of these plants is Guatemala, trading about 250,000 kg per year and while the USSR sells about 70,000 kg per year [5].
The commercial value of some Cymbopogon species is further enhanced by their ability to grow in moderate and extremely harsh climatic conditions [6]. In environments where they are not used for cosmetics, drug or perfumery, such as in the Eastern Cape Province of South Africa, these plants have found a good application as roof thatches and grass brooms [7].

Ethnopharmacology of Cymbopogon Species
Traditional applications of Cymbopogon genus in different countries shows high applicability as a common tea, medicinal supplement, insect repellant, insecticide, in flu control, and as anti-inflammatory and analgesic. Table 1 shows the common names of some species, their relevance and how they are applied. C. citratus is ranked as one of the most widely distributed of the genus which is used in every part of the world. Its applications in Nigeria include cures for upset stomach, malaria therapy, insect repellent and as an antioxidant (tea) [8]. C. citratus and C. flexuosus are the prevailing species in Eastern and Western India and have been used locally in cosmetics, insecticides, and for the treatment of digestive disorders and fevers [9,10]. In the Middle East, C. olivierri and C. parkeri are more predominant, and they are used as antiseptics, anti-malarial condiments, diuretics and also to cure rheumatism [12,14,15]. The high amounts of volatile compounds from these species are responsible for their diverse uses.

Phytochemistry
The enormous information gathered from the ethno-pharmacological applications of Cymbopogons begged the investigation of its chemical constituents. These studies have led to the isolation of alkaloids, volatile and non-volatile terpenoids, flavonoids, carotenoids and tannins from every part of these plants. Figure 1 displays some of the compounds isolated from Cymbopogon species.

Alkaloids
The rhizome of C. citratus from Nigeria was reported to contain about 0.52% alkaloids from 300 g plant material [36].

Non-Volatile Terpenoids
Plants in the Cymbopogon genus contain large amounts of volatile terpenoids though a few species from this genus are reported to contain non-volatile terpenoids as well. Bottini et al. [40] isolated a novel bis-monoterpenoid named cymbodiacetal (22) from C. martinii. The triterpenoids cymbopogone (23) and cymbopogonol (24) (Figure 1) were also reported from the leaves of C. citratus [41].

Tannins
A literature search on the phytochemical screening of C. citratus also reveals the presence of tannins, however, very little effort has been made in the isolation of these compounds despite the appreciable amounts reported through quantitative phytochemical tests. Figueirinha et al. fractionated extracts of the species collected from Portugal and reported about 10 mg dry weight of hydrolysable tannins (prothocyanidins) [66] while C. citratus from Nigeria showed about 0.6% of tannins [36]. C. citratus is the single species of Cymbopogon which is most exploited for its tannin content.

Pharmacology
Several bioassays have confirmed the potency of Cymbopogon species for their several uses (Table 3). C. citratus was found to have chemoprotective activity by preventing of diethylnitrosamine (DEN)-initiated hepatocellular lesions in rats [67]. In South Africa, extract from C. citratus was applied for treatment of oral thrush in patients who tested positive to HIV/AIDS and proved effective [68].
Insecticidal activity is one of the biological effects of most plant of the Cymbopogon genus; it is either applied as pest control for stored crops or as mosquito repellent/ insecticide. The essential oils of C. martinii have been studied and found to display high anthelmintic activity against Caenorhabditis elegans at ED50 value of 125.4 µg/mL, C schoenanthus, C. giganteus and C. citratus essential oils from Benin Republic in West Africa all displayed about 100% mortality rate against adult Anopheles gambiae [69]. The essential oil from C. winterianus caused a dose dependent mortality of Culex quinquefasciatus with LC50 of 0.9% [70].
The anticancer properties of Cymbopogon species have also been studied. The essential oils of C. flexuosus was effective in inhibiting the growth and killing of Ehrlich and Sarcoma-180 tumors cells. In this study, it was discovered that at a dose of 200 mg/kg, Ehrlich solid tumor inhibition was about 57.83% compared to the 45.23% inhibition observed with 5-fluorouracil (22 mg/kg) [71]. Inhibition of early phase of hepatocarcinogenesis was also observed in C. citratus [67]. Positive results in several other bioassays such as antiprotozoal, anti-inflammatory, antimicrobial, anti-bacterial, anti-diabetic, anticholinesterase, molluscidal, antifungal and larvicidal activity are also prominent with Cymbopogon species as outlined in Table 3. C. densiflorus Stapf Antibacterial Gram-negative bacteria. MICs were found to be between 250 and 500 ppm for the Gram-positive and between 500 and 1000 ppm for the Gram-negative bacteria [79] C. ambiguus Inflammatory Inhibition of ADP-induced human platelet serotonin release in the cell. [

Conclusions
Cymbopogon species have been used as traditional medicine in many countries. Of all the species reviewed, C. citratus and C. flexuosus are the most widely used in traditional and in conventional medicine due to the pharmacological potential of their phytochemicals. The majority of these species contain a voluminous amount of essential oils which have shown several biological activities such as insecticidal, anti-protozoan, anticancer, anti-HIV, anti-inflammatory and anti-diabetes effects.