25

CHAPTER – II

REVIEW OF LITERATURE

2.1 INTRODUCTION

Plants have been the major source of drugs in Indian System of Medicine and other

ancient systems of medicine in the world. Medicinal plants form the most important source

of life saving drugs. A multidisciplinary approach combining botanical, ethnobotanical,

phyto-chemical and biological techniques led to drug discovery from plant [25]. Therapeutic

properties of medicinal plants are very useful in healing various diseases and keeping us

healthy. The advantage of drugs being used from these medicinal plants is they being 100%

natural products.

Gentians have been known as a medicine from antiquity and many of the complex

preparations handed down from the ancient Greek and Arabian physicians include it among

their ingredients. Plants belonging to this genus are best known for their bitter taste that is

due to the secoiridoids (e.g. Swertiamarin, Gentiopicroside, Sweroside and Amarogentin)

[26]. These are popular ingredients of many gastric herbal preparations and dietary

supplements. As natural sources of food flavouring they are utilized in alcoholic and

nonalcoholic beverages [27]. The dried root and rhizomes of several Gentianaceae species

are widely used throughout the world as hepatoprotective agents (quench the fire of the liver

and gallbladder), remedies for poor appetite and digestive problems [26]. Gentiana kurroo ,

Royle.; Gentiana chirayita, Roxb. are from the natural order Gentianaceae ; Agothetes

chirata syn. Ophelia chirata D.C. and Swertia chirayita (Roxb. ex Fleming) H.Karst. are

also from the same family.

Gentianaceae is a family of flowering plants comprising approximately 70-80 genera

and 900-1200 species. The plants of the family are annual and perennial herbs or shrubs.

They are native to Northern temperate areas of the world. According to the study of Daniel

and Sabnis [28], the plants belonging to genus Getianaceae are very well known for their

important pharmacological properties. Clarke divided Gentianaceae into three tribes:

Exaceae, Chironeae and Swertieae [29]. Cronquist treated the family under order

Gentianales of subclass Asteridae and class Magnoliopsida [30].

26

The medicinal properties of the genus Swertia (Gentianaceae) are well recognized in

different parts of the world, especially in Asia. The genus is held in high esteem in the Indian

System of Medicine and is one of the top five drugs of Kampo medicine in Japan [31]. This

species was first introduced in the Edinburgh Pharmacopoeia (England) in 1839. Swertia

is named in the honour of Emanuel Swert a Dutch gardener.

Swertia chirayita (Roxb. ex Fleming) H.Karst is official in Indian Pharmacopoeia

[19]. It is called as elixir and immersion in American and British pharmacopoeias [32].

Chunekar [33] described that Swertia chirayita (Roxb. ex Fleming) H.Karst as the principal

species of Swertia in ancient medical texts of India.

Atkinson [34] described Ophelia chirayita, Griseb, Agathotes chirayita, Don.—Tita-

khana, chirayita. He writes “Some call this species the true Dakhini chiretta or true Nepal

chiretta. The former name is properly applied to a South Indian species, Andrographis

paniculata, and the latter name may perhaps suit, as chirayita. Equally good chiretta is

obtained from Ophelia purpurascence, Ophelia cordata, Ophelia speciosa, Agathotes

angustifolia and Agathotes alata.” All yield a valuable bitter extract used as a tonic and

febrifuge and corrector of bilary disturbances.

Kirtikar and Basu [21] described that the entire plant of Swertia chirayita is used in

Traditional Medicine Systems but the root is the most powerful part. The plant is gathered

during the late stages of flowering, commonly tied up in fattish bundles about 3 ft. long and

1.5 to 2 lbs in weight [23], and is sold in the market as dried brownish stems with root and

leaves intact.

A compound preparation called “Sudarshana Churna” prepared by taking equal parts

of 54 different substances and of Chirayita equal to half the weight of all the other

ingredients and mixing them together is largely prescribed in chronic febrile diseases [24].

Herbal medicines such as Ayush-64, Diabecon, Menstrual syrup and Melicon V ointment

contain Chirayita extract in different amounts for its antipyretic, hypoglycemic, antifungal

and antibacterial properties [35]. Ayurvedic pharmacopoeia [36] indicated the value of total

ash, acid-insoluble ash, alcohol soluble extractive and water-soluble extractive for identity,

purity and strength of Swertia chirayita.

The import and export policy of India 2002-03 has placed Swertia chirayita as a

species prohibited for export in the listed 29 plant species. Swertia chirayita is one of the

most important medicinal plants of Himalayan region, which has become endangered [37].

27

2.2 SUBSTITUTES AND ADULTERANTS

Several species of Ophelia and related plants go by the name of Chirayita in India.

These are designated by the natives as bill (puharee) chirata, sweet (meetha) chirata, purple

(ooda) chirata, and southern (dukhunee) chirata. Chota chiretta, or small chiretta is the

product of Slevogtia orientalis, Grisebach.The species of Ophelia referred to above are the

Ophelia angustifolia, Don (less bitter than chirayita); Ophelia elegans, Wight; Ophelia

densifolia, Grisebach; Ophelia multiflora,Dalz; Ophelia pulchella, Don. These all possess,

more or less, the bitter tonic virtues of Chirayita. However, Swertia chirayita plays dominant

role in trade and is considered to be superior in medicinal quality. Due to high commercial

demand, Swertia chirayita has a very special niche medicinal plants in Nepal and India. One

of the main issues in its trade is adulteration with other low-value species considered to be

inferior in medicinal quality [38]. Pant and Bimb [39] mention that Swertia nervosa is the

main substitute of Swertia chirayita . Other species which are generally mixed with Swertia

chirayita are Swertia angustifolia Buch.-Ham. ex D. Don, Swertia. ciliata (D.Don ex G.

Don) B.L. Burtt, Swertia dilatata C.B. Clarke, Swertia racemosa (G.Don) C.B. Clarke,

Swertia alata (Royale ex D. Don) C.B. Clarke, Swertia tetragona Edgew , Swertia

multicaulis D.Don, Swertia paniculata etc. [38, 40]. Sometimes adulteration occurs due to

misidentification of other species as true species.

Swertia chirayita is traditionally used for the treatment of chronic fevers and liver

disorders. It has been recognized in Sushruta Samhitaa as antiseptic and curative of fevers,

urinary disorders, skin diseases, cough, and hiccup and poisoning. In Charak Samhita, it

has also been recommended as a purifier of breast milk. In Bhavaprakasha Nighantu it has

been cited as laxative (sara), causes dryness (ruksha), is cooling (sheetal), bitter in taste

(tikta), and easily digestible (laghu). It destroys cough (kaasa), oedema (shotha), morbid

thirst ( trisna), obstinate skin diseases (kushtha), fevers (jvara), ulcers (vrana), and parasitic

infections (krimi). In addition it is also employed as remedy for dyspepsia, hyper acidity in

the stomach, diarrhoea, haemorrhagic diseases, liver and kidney disorders, and is considered

a carminative, alternative, and restorative [41, 42]. Concoction of chirayita with cardamom,

turmeric and kutki is given for gastrointestinal infections and along with ginger it is

considered good for fever [21]. When given along with Neem, Manjistha and Gotu kola, it

serves as a cure for various skin problems. It is also used in combination with other drugs in

cases of scorpion bite [24]. Parajulie et al. [43] reported the use of Swertia chirayita for

28

dying cotton cloth to yellow and also for the flavoring agents by the liquor industry. It has

also been reported to be an effective insecticidial in killing larvae of Aedes aegypti mosquito

[44].

2.3 CHEMICAL COMPOSITION

Swertia chirayita is reputed for its medicinal and pharmaceutical value. This

medicinal plant species is a rich source of alkaloids and flavanoids, many of which exhibit

broad spectrum activities. The roots are supposed to possess significant antipyretic and

analgesic properties and a high therapeutic index. Various studies have been carried during

the last two decades on the isolation, identification, structural elucidation of active

constituents of Swertia chirayita and their pharmacological activities. Chirayita is found to

have a number of chemical constituents. More than twenty Polyhydroxylated Xanthones

have been characterised, and some of these are Swertinin, Swerchirin, Mangiferin,

Decussatin and Isobellidifolin. Brahamchari et al. [45] have investigated that Mangiferin is

the most common C-glycisides in Swertia chirayita. Xanthone in Swertia chirayita were

determined by HPLC [46].

Fig. 2.1 Structure of Mangiferin [47]

The Liquid chromatography/tandem mass spectrometric study and analysis of

Xanthones and secoiridoid glycoside composition of Swertia chirayita was studied by

Survanshi et al. [48], Karan et al. [49], and Kaur [50] studied the chromatographic

comparison of certain Indian species of Swertia and compared their morphological

characteristics. Morphological and chemotypic comparisons of certain Indian species of

Swertia were studied by Bhatia et al. [51]. Suryavanshi et al. [48] reported that different

29

species of the Swertia genus possesses different chemical compositions and constituents.

Tomimori et al. [52] reported flavonoids and xanthonic constituents of Nepal origin Swertia

chirayita.

Amarogentin and Swerchirin are the important phytochemicals for drug

reinforcement. Amarogentin (secoiridoid glycoside) is one of the most bitter compounds

known, and the bitter taste persists even at a dilution of 1g in 14000 litres of water [19]. It

acquires topoisomerase inhibition, chemo-preventive and antileishmanial effects [53].

Fig. 2.2 Structure of Amarogentin (secoiridoid glycoside) [47]

Fig. 2.3 Structure of Swerchirin [47]

2.4 ELEMENTAL ANALYSIS

Negi et al. [71] analyzed some trace elements and electrolytes in the Swertia

chirayita roots and leaves by atomic absorption spectroscopy. The concentration of elements

were found in the order K>Ca>Fe>Na>Mn>Zn>Co>Cu>Li in different samples of Swertia

30

chirayita. The presence of essential trace elements in Swertia chirayita will be useful for the

most of the therapeutic efficiencies and deciding the dosage of herbal drugs prepared from

Swertia species in the treatment of various diseases.

Inam et al. [72] investigated the presence of following K, Ca, Cl, S, Fe, Al, P, Si,

Mg, Rb, Ti, Mn and Na heavy metals in methanolic extracts of Swertia chirayita by X-ray

fluorescence (XRF) scanning. From their investigation they reported that the plant is a good

source of essential heavy metals.

Ata et al. [73] studied on the leaves of Swertia chirayita for their medicinal value and

found these elements Na, K, Li, Ca, Mg, Fe, Zn by flame emission spectroscopy and atomic

absorption spectroscopy. It was also investigated that the level of essential elements was

higher as compared to trace elements as Zn, Pb, Mn, Cu, Ni, Cr and Cd were not detected,

depicting their lesser concentration in the plant.

A brief consolidated chemical compounds isolated from Swertia chirayita and their

pharmacological properties reported are presented in Table 2.1.

Table 2.1: Chemical Constituents of Swertia chirayita

S. No. Secondary Metabolite Reference

1. Amarogentin Asthana et al. 1991 [54] ;

Chakravarty et al. 1991 [55]

2. Amaroswerin Asthana et al. 1991 [54] and

Korte, 1955 [56]

3. Β-Amyrin Sharma,1983 [57]

4. Β-Sitosterol-3-β-D-glucoside Chaudhuri et al. 1996 [58]

5. Chiratanin Chaudhuri et al. 1996 [58]

6. Chiratanol Hatjimanoli et al. 1988 [59] ;

Mandal et al. 1987 [60]

7. Chiratol/1,5 dihydroxy 3,8-

dimethoxy xanthone

Dalal and Shah,1956 [61] ;

Chakravarty et al. 1992 [62];

Purushothamam et al. 1973a [63]

8. Decussatin Dalal and Shah,1956 [61] ;

Chakravarty et al. 1992 [62];

Purushothamam et al. 1973a [60]

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S. No. Secondary Metabolite Reference

9. Enicoflavin Dalal and Shah,1956 [58];

Chakravarty et al.1992 [62];

Purushothamam et al. 1973a [63] 10. Episwertenol Hatjimanoli et al. 1988 [59]

11. Erythrodiol Mandal et al.1987 [60] ;

Sharma,1982 [64]

12. Gammacer-16en-β-ol Korte, F., 1955 [56]

13. Gentianine Purushothamum et al. 1973b [65]

14. Gentiocrucine Purushothamum et al. 1973b [65]

15. Kairatenol Chakravarty et al. 1992 [62]

16. Lupeol Chajravarty et al. 1992b [66]

17. Mangiferin Ghosal et al. 1973 [67];

18. Mangostin Mandal et al. 1992 [68]

19. Oleanlic acid Chaudhuri et al. 1996 [58] ;

Sharma,1983 [57]

20. Pichierenol Chakravarty et al. 1992 b [66]

21. Sweroside Chakravarty et al. 1994 [69]

Chaudhuri et al. 1996 [58]

22. Sweroside-2’-o-3”,5-trihydroxy

biphenyl-2” carboxylic acid

ester

Chaudhuri et al. 1996 [58]

23. Swerta-7,9(11)-dien-3 β-ol Chakravarty et al. 1992 b [66]

24. Swertanone Chakravarty et al. 1991 [55]

25. Swertenol Chakravarty et al. 1991 [55]

26. Swertianin/1,7,8-trihydroxy-3-

meyhoxy xanthone

Purushothamum et al. 1973 b [65],

Sharma,1982

27. Syingaresinol Chakravarty et al. 1994 [69]

28. Taraxerol Chakravarty et al. 1991 [55]

29. Ursoilic acid Chakravarty et al.1991 [55]

32

S. No. Secondary Metabolite Reference

30. o-Taraxasterol or heterolupeol Sharma,1982 [64]

31. 1,3,5,8-tetrahydroxy xanthone Verma et al. 2001 [70]

32. 1,3,7,8-tetrahydroxy xanthone Verma et al. 2001 [70]

33. 1,3,8-trihydroxy-5-methoxy

xanthone

Verma et al. 2001 [70]

34. 1,5,8-trihydroxy-3-methoxy

xanthone

Verma et al. 2001 [70]

35. 1,8-dihydroxy3,5-dimethoxy

xanthone/swerchirin

Verma et al. 2001[70] ;

Chakravarty et al. 1994 [69];

Dalal and Shah,1956 [61]

36. 1-8-dihydroxy-3,7-dimethoxy

xanthone/7-O-methylswertanin

Verma et al. 2001 [70] and

Dalal and Shah,1956 [61]

37. 1-hydroxy3,5,8-trimethoxy

xanthone

Verma et al. 2001 [70] and

Asthana et al. 1991 [54]

38. 1-hydroxy3,7,8-trimethoxy

xanthone

Verma et al. 2001 [70] and

Asthana et al. 1991 [54]

39. 2,5-dihydoxyterephthalic acid Chakravarty et al. 1994 [69]

40. 21-α-H-hop-22(29)-en-3-β-ol Hatjimanoli et al. 1988 [59]

2.5 PHYTOCHEMICAL ANALYSIS

Pant et al. [74] investigated phytochemicals and their biological activities from genus

Swertia. Manjunath et al. [75] also studied on preliminary phytochemical and wound healing

activity in the root extract of Swertia chirayita. Bhandari et al. [76] determined active

constituents, swertiamarin and amarogentin in Swertia species from the Western Himalayas

region by HPTLC. Brahmachari et al. [45] investigated Chemical and pharmacological

aspects of Swertia genus (Gentianaceae).

Negi et al. [46] studied on qualitative and quantitative estimation of therapeutically

active constituents. They used HPLC technique by using different stationary and mobile

phases for the separation of different xanthones in genus Swertia. Negi et al. [46] reported

that genus Swertia contains active constituents Xanthones and different secondary

33

metabolites like flavonoids, irioid glycosides and triterpenoids. These constituents are

responsible for hepatoprotective, antimicrobial, antimalarial and other different

pharmacological activities.

Phoboo et al. [77] analysed the main phytochemicals in crude aqueous and ethanolic

extracts of different plant parts of Swertia chirayita from nine different districts of Nepal and

were quantified using HPLC/DAD (High Performance Liquid Chromatography- Diode

Array Detection). The quantities of these phytochemicals were also compared between wild

and cultivated plant parts of Swertia chirayita. Amarogentin, mangiferin, swertiamarin were

the main phytochemicals in all extracts [78].

2.6 ANTIMICROBIAL ACTIVITIY

Bhargava et al. [79] evaluate the antimicrobial activity of aqueous extract of

Sudarshan Churna using the paper disc diffusion method. He observed that the aqueous

extract of Sudarshan Churna is active against the gram-negative bacteria Klebsiella

pneumoniae, Escherichia coli, and gram-positive bacteria Staphylococcus aureus, Proteus

vulgris and found less effective against gram-positive bacteria Staphylococcus epidermidis

and Bacillus subtilis. The aqueous extract of Sudarshan Churna shows significantly less

effect against Candida Albicans. Bhargava [80] also investigated antibacterial activity of

aqueous root extract of Swertia chirayita.

Sultana et al. [81] demonstrated the antibacterial activities of Swertia chirayita. They

prepared extract of the plant by using the fresh stem in rectified spirit and pure compound.

Laxmi et al. [82] evaluated antimicrobial activity in methanol and aqueous extract of

Swertia chirayita against 10 bacteria and 3 fungi by agar diffusion method. They used

gentamycin and amphotericin as standard drug for antibacterial and antifungal activity. The

result showed that methanolic extract showed maximum activity than aqueous extract.

Malik et al. [83] studied on Swertia chirayita along with twenty three medicinal

plants for antimicrobial activity and they reported that the aqueous and alcoholic extract of

Swertia chirayita have good activity against most of the microorganisms.

Generally the methanol extract was more active than other extracts against the

selected bacterial isolates and fungus, because most of the antimicrobial agents in plants are

soluble in methanol [84]. This may be attributed to the presence of soluble phenolic and

polyphenolic compounds [85].

34

2.7 ANTIOXIDANT CAPACITY

Saha and Das [86] found that Swertia chirayita demonstrated the immune

suppressant action. Modulation of liver detoxification and protection from anti-oxidative

damage were also reported. Khanom et al. [87] observed a strong superoxide scavenging

action of the plant in methanollic extract. Scartezzini and Speroni [88] also reported

antioxidant activity of Swertia chirayita.

Pauletti et al. [89] reported that mangiferin is an important constituent of plant

possesses free radical scavenging property. Balasundari et al. [90] investigated free radical

scavenging xanthones and tumor cell growth inhibition from Swertia chirayita.

Tripathi et al. [91] reported the comparison between Green Chirayita (Andrographis

paniculata) and Real Chirayita (Swertia chirayita) and found that Swertia chirayita has

good efficient natural antioxidant properties.

Gupta and Sharma [92] described that xanthones, mangiferin, swertianin and chiratin

are responsible for antioxidant potential of Swertia chirayita.

2.8 ANALGESIC ACTIVITY

Alam et al. [93] investigated the analgesic activity of ethanol extract of leaf, stem,

and their different fractions i.e. petroleum-ether, dichloromethane and methanol fraction of

Swertia chirayita on Swiss albino mice by Acetic acid induced writhing method. The ethanol

extract of leaf and stem of Swertia chirayita showed moderate inhibition (p<0.001) of

writhing. Among different fractions petroleum-ether fraction showed significant inhibition

(p<0.0001) of writhing whereas methanol fraction showed moderate inhibition (p<0.003) of

writhing as well. The inhibition of writhing was calculated in respective to control (vehicle).

The test samples were administered at a dose of 200 mg/Kg body weight of experimental

animals with diclofenac sodium at a dose of 25 mg/Kg body weight was used as standard

drug in their study.

Jha et al. [94], analysed that methanolic extract of aerial parts of Swertia chirayita

produced dose dependant and significant inhibition of carrageenan induced paw oedema and

analgesic activity in rats. Henceforth the extract is being reported for anti-inflammatory and

analgesic properties particularly by attenuating the peripheral pain mechanism.

Chandra et al. [95] studied ethanolic root extract of Swertia chirayita for analgesic

and anti-inflammatory activities in animal models. They assessed the anti-inflammatory

35

activity by using the carrageenan-induced rat paw oedema model and the analgesic effect

was measured using the acetic acid-induced writhing test and the radiant heat tail-flick

method in mice. They reported that Swertia chirayita, can be traditionally used against

inflammation and pain.

2.9 ANTIPYRETIC ACTIVITY

Bhargava et al. [96] also studied on antipyretic potential of Swertia chirayita in root

extract. The aqueous extract of Swertia chirayita was evaluated for its antipyretic potential

on Brewer’s yeast-induced pyrexia in albino rats and typhoid-paratyphoid A, B vaccine

induced hyperexia in rabbits. In both models, the extract, at dose of 200 mg/kg body weight

and 400 mg/kg body weight, produced significant (p<0.001) reduction in elevated body

temperature in a dose dependent manner. The antipyretic effect of the extract was

comparable to that of paracetamol (150 mg/kg body weight), a standard antipyretic agent.

Duraisanka and Ravichandrana [97] studied the polyherbal formula with Swertia

chirayita as one of the ingredient and found positive result of antipyretic activity.

2.10 OTHER PHARMOCOLOGICAL ACTIVITIES OF SWERTIA CHIRAYITA

There are a number of chemical constituents of Swertia chirayita that are responsible

for its various medicinal properties that resulted in the detailed scientific documentation

about the various active components of the plants and their properties.

Table 2.2 Pharmacological properties of Swertia chirayita

S. No. Properties References

1. Alterative Duke, 2002[20] ; Duke et al. 2002 [98]

2. Antithelmintic Ray et al. 1996 [53]

3. Antileishmaniak Medda et al. 1999 [99]

4. Anticholinergic Raffatullah et al. 1993 [100]

5. Anticonvulsant Bhattacharya et al. 1976 [101]

6. Antiedemic Blaschek et al. 1998 [102]

7. Antinflammatory Korte,F.,1955 [56]

Islam et al. 1995[103]

Kumar et al.,2002; Banerjee et al.,2000

36

S. No. Properties References

8. Antimalarial Goyal et al. 1981[104]

9. Antipyretic Blaschek et al. 1998 [102]

10. Antitubercular Kamatsu et al. 1971 [105]

11. Astringent Nadkarni,1976 [24]

12. Bitter Dalal and Shah,1956 [61]

13. Cardio stimulant Blaschek et al. 1998 [102]

14. Cholagogue Kirtikar and Basu ,2006 [21]

15. Choleretic Blaschek et al. 1998 [102]

16. CNS depressant Ghosal et al. 1973 [67]

17. Emollient Duke, 2002 [20] ;

Sharma,1983 [57] 18. Hepatoprotective Mukharjee et al. 1997 [106]

19. Hypnotic Duke, 2002 [20];

Ray et al. 1996 [56]

20. Hypoglycemic/Antidiab

etic

Mukharjee et al. 1978 [107];

Grover et al. 2002 [108]

21. Laxative Duke, 2002 [20];

Ray et al. 1996 [53] 22. Secretagogue Kirtikar and Basu 2006 [21]

23. Stomachic Nadkarni,1976 [24]

24. Tonic Nadkarni,1976 [24]

25. Vermifuge Kirtikar and Basu 2006 [21]

The combined studies of elemental analysis, phytochemical and pharmacological

activities of Swertia chirayita antimicrobial, analgesic, antipyretic and antioxidant capacity

have not been reported in Garhwal Himalayas from any quarter. The present study makes

these studies to prove a clue for assistance of in ex-situ conservation for selective

chemotypes of germplasm and improve the quality of production of Swertia chirayita for the

society.

………………..