Pharmacological Activities of Phytoconstituents and Essential oil obtained from Cymbopogon citratus Linn.

 

Prabhat Kumar Upadhyay, Prakhar Dixit, Debapriya Garabadu

Institute of Pharmaceutical Research, GLA University, Mathura - 281406, Uttar Pradesh, India.

*Corresponding Author E-mail: pkutanu@gmail.com

 

ABSTRACT:

Cymbopogon citratus (Lemon grass) is well known medicinal herb and distributed in various regions of tropical countries South East Asia. The various parts such as leaves and whole plant of lemongrass are used in the herbal therapies. The essential oil consists of mostly terpenes, aldehyde, ketones, alcohol and esters. Cymbopogon citratus possesses wide range of pharmacological activities including antibacterial, antifungal, antidiarrheal, antifilarial, anti-amoebic and anti-inflammatory. In addition to them, antimalarial, antimycobacterial, hypoglycemic antioxidant, antimutagenicity, and CNS activities were reported. The secondary metabolites like saponins, tannins, anthraquinones, flavonoids, alkaloid phenols and also active constituents from essential oil (such as citral, limonene and terpineol) obtained from the plant are responsible for pharmacological activities. The antioxidant properties of lemongrass help in lowering the risk of cancer through scavenging of free radicals. In this paper, the study emphasizes on systematic study on the potential benefits of plant in the management of various diseases. Therefore, the phytoconstituents and major active constituents from essential oil, determines medicinally properties of lemon grass. The possible mechanisms of action has also been explored in case of some diseases.

 

KEYWORDS: Lemon grass, Ethnopharmacology, Pharmacological activities, Immunomodulatory activity.

 

 


INTRODUCTION:

Lemon grass is an aromatic and perennial tall grass having fibrous root, rhizomes, segmented small underground stems and rough green sleathery leaves1. The leaves and whole plant of lemongrass is used for medicinal purpose. Taxonomically, it is placed in class- liliopsida and family-poaceae. The botanical name of lemaon grass is Cymbopogon citrates which is also known as Citronella (in English), Sera verveine (in Hindi), Tej sar (in Ethiopia), lemongrass (in Egypt), Cymbopogon (in Italy). It is a herb obtained from India which is cultivated in the tropical and subtropical regions of Asia, Africa and America2. The 144 species of Cymbopogon are reported which produce the essential oils in high yield. The oil has been utilized in perfumery, pharmaceutical and cosmetic industries3.

 

Commercially, Cymbopogon species grow more efficiently in moderate and extremely callous climatic conditions4.  The plants have applications in preparing grass brushes and roof coverings5. Apart from these applications, essential oil and extract of C. citratus have wide range of pharmacological activities6. This medicinal plant is used to treat various health conditions like diarrhea, constipation, heat burn, bloating etc. and used as anti-inflammatory, antipyretic, antibacterial, anti-fungal, astringent, anti-cancer, antidepressant, and insecticidal properties. While, lemongrass tea is also used for improving digestion. Citral, an active constituent of lemon grass, slows down breast cancer cell growth. The antioxidant properties of lemongrass help in lowering the risk of cancer through scavenging of free radicals. The different parts of lemon grass are useful in the herbal therapies7. From investigations, it has been found that specific part of the plant used, method of extraction, season of harvest, genetic differences and geographical origin are the determinants of the availability of chemical constituents in C. citratus8. Despite these differences, a number of classes include anthraquinones, saponins, tannins, alkaloid phenols, and flavonoids have been examined. The active constituents like citral, geranial, nerol,  limonene, citronellol,  myrcene, burneol, α-terpineol,  apigenin, quercetin, luteolin,  kaempferol, caffeic acid, chlorogenic acid, elemicin and geranyl acetate  are found in the essential oil. Some other isolates such as isopulegol, L-linanool, furfurol, fumesol, methyl heptenone, isovaleranic aldehyde, p-coumaric acid, terpineone, valeric esters, n-decyclic aldehyde, etc. have been reported9.  They have also used as food flavour, cosmetics and food preservation10. Recent investigations suggested that essential oil C. citratus (CCEO) is used possibly as an inhibitor of oxidative biodegradation.

 

This review paper focuses on recent advances used to study the medicinal importance of lemon grass and search the possible mechanism of action, toxicities for the treatment of various diseases.

 

Botanical description:

Lemon grass is versatile and such tropical grass grows in dense clumps to the height of 6ft 1.8m and about 4ft in width having rhizome. Table 2 shows morphological features of Cymbopogon citratus11.

 

Ethnopharmacology:

Lemon grass is used in medicinal preparations for various purposes worldwide (Table 2)

 

Phytoconstituents:

The chemical composition of lemon grass oil varied in the plant upon change in the geographical distribution. The different plant parts are utilized in the herbal therapies7. A number of classes of compounds include tannins, saponins, flavonoids and anthraquinones12. The volatile oil contains compounds like alcohols, esters, ketones, terpenes, and aldehydes have been reported as ingredients of the essential oil. C. citratus contains the constituents such as geraniol, citronellal and myrcene. The major constituent of volatile oil is citral. Citral is a mixture of two isomers viz. monoterpene aldehydes. These are nerol (a cis isomer, 25-38%) and geranial (a trans isomer, 40-62%)13.

 

Pharmacological Activities:

Antioxidant activity:

The extracts in various solvents tested as inhibitors of TBARS production and observed as DPPH scavenger15. The effects can be associated to the phenolic contents, including flavonoids. Interestingly, aqueous extract of C. citratus observed as best antioxidant comparing with M. recutita and other extracts of C. citratus. Therefore, plant could be used as in the prevention of various oxidative damage based neurological diseases1.

 

The researchers examine the antioxidant activity of essential oils and search safe natural antioxidants16.  In eukaryotes, hydroxyl radicals damage the mitochondrial DNA which is produced by hydrogen-peroxide and superoxide anions (Figure1). Such damaged mitochondrial DNA inhibits the electron transport protein and reactive oxygen species (ROS) accumulates17. Thus, damaged mitochondrial membrane generates the free radicals and damages lipids and proteins in cells. The essential oil penetrates through cell membrane and combines with free radicals produce reactive phenoxy radicals which further unite with ROS. Such scavenging property of essential oil prevents further damage due to major constituents present in the essential oil18.

 

Antimicrobial activity:

The chloroform extracts of lemon grass leaves and roots showed moderate antimicrobial action against S. aureus, S. typhi while E. coli. While, C. albicans strains were found to be resistant against these plant extracts. C. citratus was observed as less antimicrobial when compared to Chloramphenicol and Ketoconazone19.

 

Antibacterial action of lemongrass oil was found to be significant against all bacterial strains except P. aeruginosa. Gram positive bacteria (S. aureus, B. cereus and B. subtilis) were found more susceptible than Gram negative bacteria (E. coli, K. pneumoniae, P. aeruginosa). Antibacterial activity increased gradually as the increase in oil concentration20.

 

In another research, antifungal activity of lemongrass was observed against Aspergillus species by measuring radial mycelia growth, MIC determination. This study suggested that oils could be used as antifungal agent in the treatment of respiratory tract infections21.

 

Antimutagenic activity:

C. citratus extract in ethanol shows an antimutagenic activity in different models. The phyto-constituents reduce growth of fibrosarcoma cells transplanted in mice as well as lung cell metastasis22. Plant extract is known to inhibit the formation of azoxymethane-induced DNA adducts and aberrant crypt foci in the rat colon23. Inhibitory effects of plant extracts have been observed in hepatocarcinogenesis in male Wistar rats.

 

Antimutagenic Activity of essential oil is to explain by different mechanisms viz. inhibition of the mutagens penetration into cells direct scavenging cause inactivation of mutagens (Figure 2), capturing radicals produced in mutagenesis by antioxidants, antioxidant enzyme activation in cells inhibiting the conversion of pro-mutagens to mutagens by P450 metabolic pathways or major constituents from essential oil activate the enzymatic detoxification of mutagens24.  

Antiulcer Activity:

In the last decade, various reports recognized the gastroprotective action of latex, constituents including terpenes, tannins, alkaloids, oleo-resins, saponins, xanthones and flavonoids. This study illustrates first time that C. citratus has gastroprotective action against the ethanol and aspirin induced gastric damage. The damage is possibly supported by oxidative stress and impaired prostaglandin in experimental models25.

 

Anxiolytic Activity:

Benzodiazepines bind on GABAA receptor at a separate GABA binding site and produce anxiolytic effect. The similar effects of essential oil (EO) occurred through GABA mimic system. A benzodiazepine-GABAA antagonist, Flumazenil was co-administered with the essential oil or Diazepam (DZP) in mice. This method explained the anxiolytic-like action of both standard DZP and essential oil.  Flumazenil antagonizes the anxiolytic-like activity of EO effectively26.

 

Antiplatelet Activity:

In this study, essential oils inhibited platelet aggregation which were characterized by constituents such as phenols (C. citratus, T. vulgaris and O. vulgaris) and phenyl propanoids (O. basilicum, O. quixos, F. vulgare and A. dracunculus), suggesting a relationship between these chemical constituents of essential oil and specific biological activities27.

 

Anti-diabetic activity:

Anti-diabetic effect of extracts of C. citrates root and   flower have been observed in dexamethasone induced hyperglycaemic animals and compared to glibenclamide, as standard drug. The root extract  possessed better  anti-diabetic  effect  than  flower extract Diabetes  mellitus  induced  by  glucocorticoids  is  similar  to  type-2  diabetes  mellitus and also  cause  obesity,  hypertension, hyperurecemia28.

 

Anti-inflammatory Activity:

The extract of C. citratus and its constituents as polyphenols suppressed production of cytokines in human macrophages. The evidences demonstrate anti-inflammatory action of such phenolic compounds in relevant human cells. The effect on NF-κB activation pathway has been observed; the results showed that inhibition by C. citratus occurs through LPS-induced NF-kB activation pathway29. In case of TNF-α biosynthesis is regulated through NF-κB pathway and also p-38 and JNK involved. Cymbopogon extracts inhibited NF-κB-dependent iNOS expression and COX-2 enzyme actions30.

 

Larvicidal Activity:

The larvicidal activity has been observed against Anopheles arabiensis. At lower concentrations, extract of C. citratus showed potent activity against A. arabiensis than Croton macrostachyus. Therefore, plant extracts is believed to have potent larvicidal action against Anopheles arabiensis. The plant extract will be useful to produce natural products which destroy mosquito life cycle31.

 

Antihypertensive Activity:

The aqueous extracts of Cymbopogon citratus are capable as antihypertensive agents who prevent increase in heart rate and blood pressure in dose dependant manner in hypertensive rats. The hypertension was induced by ethanol-sucrose and the presence of phytoconstituents such as tannins, alkaloids, flavonoids and other phenolic compounds establish the lowering of blood pressure. Antihypertensive actions of plant extracts may be due to active constituents which are responsible for cardio-protective and vasorelexant activities32.

 

Antinociceptive Activity:

Antinociceptive activity of C. citratus was observed in three experimental models (formalin test, acetic acid-induced writh test and hot-plate method). It has been concluded that activity of essential oil (EO) was established on both central and peripheral nervous systems. Antinociceptive effects of EO constituents possibly explore both central and peripheral mechanisms of action in different ways33.

 

Antimalarial Activity:

The essential oil of C. citratus was evaluated for in vivo antimalarial activity against infected mice with Plasmodium berghei. The essential oil has a significant inhibitory effect against growth of P.berghei in animal models and also in decreasing the fever34.

 

Antidiarrheal activity:

Loperamide and C. citratus extract are believed to act directly through movement of intestinal circular and longitudinal muscles. A positive correlation indicates that more time in staying of substances in the intestine by decreasing in the motility of gut muscles. C. citratus plant and its essential oil were used traditionally in gastro-intestinal disorders due to the presence of citral, an active constituent in the essential oil. The relaxant actions of C. citratus essential oil were studied through its inhibitory effects on contraction of intestinal muscles or inflammation of ileum which made a background for the treatment of the intestinal disorders like diarrhoea35.

 

Hypoglycemic and hypolipdemic activity:

The hypoglycaemia could be achieved either by increasing insulin production and release or increasing utilization of glucose in peripheral tissue. Further, it has been proved by similar effect of plant extracts observed in different experimental conditions in humans. As shown in the present study, elevation in plasma HDL levels, total cholesterol and LDL levels in dose dependent manner. The raised LDL levels lead to risk of developing ischemic heart and other cardio-vascular disorders36.

 

Anticonvulsant activity:

Traditionally, the plant infusions were used as CNS depressant action and the treatment of epilepsy. These actions were evaluated for anticonvulsant properties using essential oil (EO) from C. citratus leaves. EO acts GABA mimic neurotransmission or glycinergic pathways. The effects of EOs might also been observed on the inflammation, MPO release from human macrophils which possibly contributes to such effects of lemon grass37.

 

Immunomodulatory activity:

Essential oils showed number of action on immune system on various chemical levels which directly affect the tumour cell. EO enhances the activity of white blood cells for eliminating the microbes and foreign material from human body. The various components of oil determine cell penetration, attraction, cellular distributions and fixation of lipophilic or hydrophilic components on cell membranes. It was found that the inhalation of lemon grass essential oil improved mood and increased noradrenaline release.

 

The essential oils are used for improvement of immune function via different mediums. It has been reported as through different mediums. It has been reported a significant role in enhancement of immune function which acts by different ways viz. controlling secretion of adrenal gland hormone which results to the lessening of stress, activating immune response by removing toxin from lymph and by stimulating immune boosting cell, destructing harmful microbes (Figure 3) and other studies were reported to enhance human immune function38.

 

Anticancer activity:

Several cancer cell lines were used to study the effects of essential oil from Cymbopogon species which were evaluated in Sarcoma-180 tumor and murine Ehrlich models. The results showed that oil has potent anticancer effects observed in different apoptotic tumor cells in vivo. The oil treatment inhibited the growth of human cancer cell lines in concentration dependent manner against colon, neuroblastoma, liver, cervix and lung cancer cells. This demonstrated the variation in effects of cancer cell lines to the constituents present in Cymbopogon oil39.

 

Such treatment of oil obtained from Cymbopogon species used to HL-60 cells has been reported to trigger either extrinsic or intrinsic pathways of apoptosis (Kumar et al., 2008). The Cymbopogon citrates enters to the cell through facilated diffusion which acts through apoptotic pathway (Cascade of pathway  includes Cyt-c and Aparf-1 interaction results to form Cyt-c-Aparf-1 complex leading capacase-3 activation involving P-53 into DNA fragementation-condensation and finally, which generates cell apoptosis) against cytotoxicity induced cancer cell40 (Figure-4).

 

DISCUSSION:

The various parts such as leaves and whole plant of lemongrass and essential oil are used in the herbal therapies7 and showed pharmacological activities due to the presence secondary metabolites such as anthraquinones, saponins, flavonoids, alkaloid phenols, and tannins as well as active constituents from essential oil like citral, geraniol and terpineol.

 

The essential oil having major constituent, citral which is stereoisomeric mixture of two terpene-aldehydes viz geraniol and nerol; play a significant role in producing activities like antioxidant, antimutagenic, anticancer and immunomodulator41. The antioxidant properties of lemongrass help in lowering the risk of cancer through scavenging of free radicals. Other than this, variety applications in food and cosmetic industry.

 

The results from various studies indicates that the correlation of biological activities and presence of active constituents or molecular modifications of active constituent from essential oil has been centred to add up new activities and develop new herbal therapeutics10.

 

The advancements in the field medicinal properties of lemon grass against various diseases have been studied. Therefore, it has been suggested that essential oil from C. citratus could be utilized as an inhibitor of oxidation in biodegradation process.

 

Above discussion provides the background that new protective effects on somatic cells, nerve tissues and liver cells are to be search and investigate their mechanism and toxic effects of phytoconstituents and essential oil obtained from plant.

 

Table 1: Morphological features of Cymbopogon citratus

Plant parts

Description of plant parts

Leaves

Strip shaped leaves have a width from 0.5-1 in 1.3-2.5 cm and with a length of 3.0 feet 0.9 and glassy tips. The leaves are bluish green in colour.

Flowers

Lemon grass herb does not typically produce flowers while flowering panicles are seldom formed.

Inflorescence

30-60 cm long inflorescences while, partial inflorescences are paired racemes of spikelet.


Table 2. Ethnopharmacology of Lemon grass

Country 

Uses

India

Lemon grass is used as a sedative

USA

In the healing wounds and bone fractures

Cuba

Lowering blood pressure in catarrh and rheumatism

Brazil

Antispasmodic, analgesic, anti-inflammatory

Egypt

Renal antispasmodic and diuretic

Indonesia

Used in the emmenagogue

Malaysia

Used in the emmenagogue

 

Table 3: Essential oil composition in Cymbopogon Citratus14

Constituents of Essential oil

Components in percentage

Citral a

40.8

Citral b

32

Myrecene

0.72

Terpinolene

1.23

Geraniol

3.04

Nerol

4.18

Terpinol

0.45

Geranyl acetate

0.83

 

 

 


 

Figure 1: Mechanism of Antioxidant action

 

 

Figure 2: Mechanism of Antimutagenic activity 


 

 


Figure 3: Mechanism of Immunomodulation

 

 

Figure 4: Mechanism of apoptotic signaling pathway


 

CONCLUSION:

Lemon grass is versatile and such tropical grass grows in dense clumps to the height of 6ft 1.8m and about 4ft in width with a rhizome. From investigations, it has been found that method of propagation, habitat of the plant, genetic differences, geographical origin etc. determine the biogenetic pathways and the formation of chemical constituents in various parts of C. citratus. For example saponins, anthraquinones, tannins, alkaloid phenols and flavanoids were found in variable proportions in such plants.

 

The active constituents such as citral, limonene, α-terpineol, quercetin, elemicin, burneol, myrcene, luteolin, geranial, caffeic acid, nerol, citronellol, chlorogenic acid kaempferol, apigenin, and geranyl acetate are found in major constituents in the essential oil. More than above, plant have utilized in the perfumery, cosmetics and food. This paper focuses on recent advances based on review of existing medicinal properties and their mechanisms, toxicity studies of lemon grass. In future, the researchers may study major constituents of plant essential oil, modify their structures and to investigate new activities.

 

ACKNOWLEDGEMENT:

We are grateful to Prof Pradeep Mishra, Director, Institute of Pharmaceutical Research, GLA University, Mathura (U.P.) for providing e-resources and library facilities for this study.

 

CONFLICTS OF INTEREST:

None.

 

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Received on 19.04.2020           Modified on 27.05.2020

Accepted on 30.06.2020         © RJPT All right reserved

Research J. Pharm. and Tech. 2021; 14(9):4555-4560.

DOI: 10.52711/0974-360X.2021.00792