A Comprehensive Review on Ocimum basilicum

The genus Ocimum has a number of species that are used to treat different types of disorders and diseases from ancient times. In this genus, O. basilicum plays a vital role due to its various medicinal properties. It is universally cultivated as herbaceous, perennial plant but originated from Asian continent. O. basilicum is used as a culinary herb and also has a number of pharmacological activities to prevent or treat cardiovascular disorders, diabetes, menstrual cramps, digestive disorders, neuro-degenerated disorders and cancer. In addition to that, it has been reported for antioxidant, antimicrobial, and larvicidal activities. Chemical constituents such as linalool; eugenol; 1, 8-cineone; methyl eugenol and anthocyanins are mostly responsible for the above mentioned activities. Some traditional uses of this plant coincidences with experimental results. However, the studies conducted based on its traditional use are negligible. This review is an attempt to provide a pharmaceutical perspective of Ocimum basilicum.


Introduction
The genus Ocimum belongs to the family Lamiaceae.There are about 150 species of Ocimum 1 .The genus Ocimum has a number of species that are used to treat different types of ailments from ancient time, especially the species Ocimum basilicum 2 .It is otherwise known as sweet basil.It is a universally cultivated herbaceous, perennial plant 3 .It is a popular herb used in Italian and Southeast cuisines of Thailand and Vietnam 4 .It has numerous potent activities due to the metabolites present in it.As a consequence of its virulent metabolites, it is used in traditional medicine [5][6] and also as an ornamental plant 7 .The extracts of essential oils of Ocimum basilicum are used as the flavors for the food products.It is used as a kitchen herb, culinary herb and ornamental herb 8 .It has also been used as commercial fragrances, flavors and to improve the food products shelf life [9][10][11] .
O. basilicum has been reported numerously in areas related to agriculture, food, and pharmacology.Hence, this review would shed more lights on different dimension of O. basilicum to the researchers.At the same time, the disappearance of O. basilicum in certain regions is increasing day by day so, it is vital to create awareness on the medicinal importance of this plant to prevent its extinction.All these things made us to pen down this review which is mainly focused on the pharmaceutical prospective of Ocimum basilicum.

Perfumery
The ethanolic steam distillation extract of flowers is used as pleasant smelling compound in perfumes 26 .The presence of essential oils determines the aroma of the O. basilicum.

Biogeography and Ecology
Basil is a vital oil bearing herb which can be grown in various environmental conditions on a wide range of terrain.Among varied aromatic and medicinal crops, basil is one of the crops for utilization of sodic wasteland owing towards its tolerance to higher salt, pH and exchangeable sodium percentage 28 .Hence, O. basilicum habitation varies from tropical areas of Asia, Africa, Central and south America 1 but it is highly cultivated in Iran, Japan, China and Turkey 29 .

Phytochemical Studies
O. basilicum majorly contains about 20 compounds such as linalool, estragole, methyl eugenol, 1, 8-cineole, etc., which has been identified by GC-MS 30 .Camphor, limonene, thymol, citral, α-linalool, β-linalool, estragole, are the monoterpene's of O. basilicum.Methyl eugenol is the active compound of Ocimum basilicum.Chichoric acid was found in the fresh basil leaves 31 .Crude extract of various morphological parts of Ocimum are rich in phenolics.The intensely purple pigment of flower is due to the presence of anthocyanins 32 .Linalool (52.42%), methyl eugenol (18.74%), 1,8-cineol (5.61%) are the major compounds in O. basilicum which are isolated by the HPLC method 30 .Myrcene, borneol and neral are the minor compounds present at 5%, 9%, 8% w/w respectively.Fourteen different anthocyanins have been isolated by HPLC within that 11 has cyanidin based pigments and 3 has peonidin based pigments 32 .It is also used in the preparation of cosmetics and perfumes.Extracts of Ocimum show strong inhibitory effects on HIV-1 reverse transcriptase and platelet aggregation 33 .Chemical constituents of O. basilicum and their biological activity are shown in Table 2.The chemical structures of O. basilicum constituents are shown in Figure 1.

Effluent Treatment
Over 50,000 tons of diverse artificial colorants are yearly produced as of many industrialized processes and around 1-10 % of them are settled into the surroundings 84 .Due to synthetic source and compound molecular structure, dyes are challenging to biodegrade when at large to the environment and their half-finished degradation frequently produces toxic compounds 85 .There are   several methods which are active to reduce the dyes 86 .
Coagulation-flocculation is one of the furthermost effective and inexpensive processes for treatment of wastewater containing dye 87 .The plant-based coagulants are harmless to human health, cost effective and biodegradable 88 .They produce a lesser amount of sludge and do not modify pH of the treated water 89 .The Ocimum basilicum was used as a natural coagulant for the treatment of textile waste water 84 .The seeds obtained from this plant are also used for biosorption of copper 90 .
The plant is also used as a potential bio-sorbent for chromium uptake with its high biosorption capacity of the seeds 91 .The plant is adaptable for all soil conditions, this plant also adaptable to grow in sodic soil which was proved by the bacterial isolates from the soil where it is isolated 91 .

GC-MS
In GC-MS, helium gas Agilent-Gas chromatography was equipped with HP-innowax fused silica capillary column (30 mm × 0.25 mm, film thickness 025 µm) 29 .The GC-MS analysis were performed with a carloErba HRGC 5160 mega gas chromatography equipped with FID and a Hitachi 2000 integrator 15 .For the different types of basil Automated HS-SPME of basil, volatiles was performed using a CombiPal multipurpose sampler connected to a GC-ITMS system [92][93][94] .
"Reprinted (adapted) with permission from Effect of Chitosan on the Biological Properties of Sweet Basil (Ocimum basilicum L.) 95 ".
The GC-MS study (Figure 2) confirms the presence of terpenoids such as eugenol, methyl eugenol, 1, 8-cineole, L-linalool, bergamotene in the methyl tert-butyl ether extracts of O. basilicum at different retention time.It also reveals that the eugenol has the higher percentage (33%) in the composition when compared with others.Identification of these compounds was done by GC-MS equipment from Shimadzu, model no: GC-17A with a DB-5 capillary column (60mm-0.25 mm, thickness 0.25 µm) and the detector used was GCMS-QP 5050 mass spectrometer 50 .

SEM
A SEM study has examined the leaves at various stages of development which is dehydrated in the ethanolic series and the solvent-substituted liquid carbon-dioxide and sputter coated with gold.The material was examined using a Jeol JSM 35 SEM 96 .

HPLC
The aqueous extract of basil has been separated to specific compounds with the help of HPLC 21 .The injector and detector parts of the HPLC are maintained at 523 K and 573 K respectively 97 .Rosmarinic acid and caffeic acid were quantified in all basil samples using a dual pump waters HPLC system 98 .The Identification of the essential oil compounds was based on the retention time 99 .It has been proved by the presence of peaks in various retention time at 280 nm.For the above analysis, Shimadzu LC-10 AS with diode array detector (Shimadzu, SPD-10A) and the reverse phase Spherisorb ODS II (RP18), analytical column (250 mm× 4.6 mm, particle size 5 µm) was used.

Antimicrobial
Numerous therapeutic plants have its own antimicrobial agents have gained popularity in recent years 26 .Due to the accidental and extensive practice of antibiotics for the action of infectious and communicable diseases, the pathogenic microorganisms remain developed into multiple disease resistance at recent years 108 .One of the finest methods toward to resolve this problem is to look for new therapeutic agents from plants which contain antimicrobial activities against the pathogenic microorganisms 109 .Extracts obtained from Ocimum basilicum has a rich source of flavor compounds and volatile oils which contain variety of compounds and these compounds possess antimicrobial activity 106,33 .The essential oil from O. basilicum is shown to have an inhibitory effect on Aspergillus ochraceus 110 .The hairy root cultures of Ocimum basilicum is used to achieve antimicrobial activity against bacteria and fungi by inhibiting z ++ ion assays in contradiction of the organisms such as P. aeruginosa strains (PAO1) (PA14), A, rhizogenes, P. fluroscens, X. campestris, E. carotovora, P. drechsleri, Phytopthora megasperma, Phytophthora parasitica, A. niger, Rhizoctoniasolani, F. oxysporum, P. aphanidermatum, P. ultimum, Versicillium dahailia, Alternaria solani and Alternaria brassicae 111 .The leaf extract is prepared into a powder and soaked with 95% ethanol and kept free of oil obtained from this plant also shows antimicrobial activity by ethanoic extracts from its leaves which were observed against E. coli and Staphylococcus aureus with its inhibition level 26 .Anti-fungal activity of the O. basilicum is performed in 2045 fungal species which showed more effect on the Aspergillus flavus which is toxigenic in nature 112 .
Basil oil also has been reported for its significant effect in in vitro studies 113 .

Antioxidant
Ocimum basilicum contains several active antioxidant compounds 114 .The oil obtained from this plant also shows antioxidant properties to assist sperm parameters and enhance sperm quality in rats to increase spermatogenesis 26 .The antioxidant property is due to the polyphenoid rosmarinic acid which is a derivative of cinnamic acid 32 .

Anti-Hyperlipidemic
The aqueous O. basilicum extract significantly lowered both plasma triglycerides (TG) and cholesterol in acute hyperlipidemia induced by Triton WR-1339 in rats 102 .

Anticonvulsant
Hydro distillation of aqueous leaf extract of Ocimum basilicum has strong anticonvulsant activity majorly due to the eugenol present in it 25 .

Anti-Inflammatory
Solvent extraction of methanolic extract of Ocimum basilicum aerial parts have potent anti-inflammatory activity against macrophage (RAW264.7),human chondrosarcoma (SW1353) cell lines and human primary chondrocytes 103 .

Insecticidal Activity
Usage of synthetic insecticides causes some significant consequences such as environmental pollution, pests or vector resistance and toxicity to other non-target creatures including human beings 107 .The vector mosquitoes are accomplished of communicating potential pathogens to human beings and them in charge for several infectious diseases like malaria, filariasis, Japanese encephalitis, yellow fever, dengue and chikungunya 115 .Moreover, the essential oil extract from the leaf O. basilicum was evaluated against Culex tritaeniorhynchus, Aedesal bopictus and Anopheles subpictus to predict the larvicidal activity 116 .It has its own significant effect against third stage larvae of Culex tritaeniorhynchus, Aedes albopictus and Anopheles subpictus with an LC 50 and 9.75 ppm and LC 90 values of 23.44, 21.17 and 18.56 ppm respectively 97 .

Immunomodulatory
The extracts from the plant Ocimum basilicum indicates its immunomodulatory action taking place in the cellular level, including platelet anti-aggregant property and inhibitory activity to counter HIV-1 reverse transcriptase 106,33 .The mechanisms underlying the hypolipidemic properties of Ocimum basilicum and anti-atherogenic potential of this plant at the cellular level is mysterious 18 .

Cytotoxicity Effect
The cytotoxicity effect of the active compounds (methyl cinnamate, linalool) of leaves extract of O. basilicum was performed by methyl thiazol tetrazolium (MTT) assay.
In Table 3, the different concentration of extracts were affected the viability of human cancer cell line such as HeLa, HEp-2 and NIH 3T3 has been tabulated along with their IC 50 value.The HeLa and HEp-2 cells were grown in Eagles Minimum Essential Medium containing 10% foetal bovine serum (FBS) and NIH 3T3 fibroblasts were grown in Dulbecco's Modified Eagles Medium containing 10% FBS.For the screening experiment, the cells were seeded into 96-well plates in 100 mL of the respective medium containing 10% FBS, at plating density of 10,000 cells per well, and incubated at 37°C, 5% CO2, 95% air and 100% relative humidity for 24 h.The essential oil was solubilized in dimethylsulphoxide (DMSO) and diluted in respective medium containing 1% FBS.After 24 h, the medium was replaced with respective medium with 1% FBS containing the oil at various concentrations (12.5,  25, 50, 100, 200, and 300 mg/mL) and incubated at the previously set parameters [63][64] .Triplicate was maintained and the medium without the oil served as control.After 48 h, 10 mL of MTT (5 mg/ 1mL) in phosphate-buffered saline was added to each well and incubated at 37C for 4 h.The medium with MTT was then flicked off and the formed formazan crystals were solubilized in 100 mL of DMSO and absorbance was measured at 570 nm using microplate reader 107 .

Diseases Affecting the O. basilicum sp
Although various medicinal properties has been exhibited by O. basilicum, it also been affected by some diseases like wilt, mold, spot and rot.Most diseases occurs in leaves and stem of basil plants due to the infection of fungi.However it can be eradicated by using proper natural fungicide to maintain its original medical nature.Some of the diseases affecting basil are shown in Table 4.

Companies Manufacturing O. basilicum Products
Basil products were commercially used all over the world for its nutritive purposes and medicinal values.Because of its multi dimensional use, many manufacturers produce basil products.Most of the basil products producing companies are located in Asian countries as shown in Table 5.

Adverse Effects and Caution
Quercetin (a flavonoid) may be a co-carcinogen in bracken fern (Pteridium aquilinum).It has been suggested that it may interact with bovine papilloma virus type 4, leading to malignant epithelial papillomas 122 .Caffeic acid and P-coumaric acid (phenolic acids) may inhibit digestion of plant cell walls in ruminants, because of their antimicrobial activity.When these phenolic acids are metabolized by rumen microbes, benzoic acid, 3-phenylpropionic acid and cinnamic acid may be formed.On further detoxification, hippuric acid is formed.
3-phenylpropionic acid and hippuric acid can decrease metabolic efficiency and also decreases productivity.Safrole, which was used to flavor sodas, was banned as a food additive in the US because it has the potential to cause cancer in rats 122 .Moreover, it should not be used during pregnancies.

Conclusion and Future Perspectives
This review majorly focused on the distinctive pharmacological activities of O. basilicum and the specific extraction procedures for the chemical constituents present in it.Basil possesses anticonvulsant, anti-hyperlipidemic, anti-inflammatory, anti-oxidant, antiplatelet property, anti-thrombotic, anti-microbial, insecticidal, immunomodulatory and cytotoxicity activities.Moreover, it also delivers those chemical constituents which is very helpful for the sustainable development of drugs for human consume.Furthermore, it also speaks about some of the manufacturers of basil products.On the converse, basil also has some adverse effects, so it should be consumed with proper prescribed medications.In the future, research may make a transgenic basil plant to eradicate the environmental stress of the plant and to address a specific chemical constituent to act against various human diseases.Here we imaged the rough and trough of basil, so it will be very helpful for the future researcher to work in different dimensions of basil to make new products.O. basilicum is the important product of nature so "we would use and should protect it".

Table 1 .
Taxonomical Hierarchy of O.