chapter 2 review of literature -...

CHAPTER 2

Review of Literature

This chapter reviews the available Ayurvedic literature on APD concept and the two pairs

of APDs selected for scientific studies. A brief introduction to trans-disciplinary research is

also provided alongside relevant research work to identify substitutes for endangered

medicinal plant species


15

2.1 Introduction

This chapter presents a systematic review of published literature on the Ayurvedic

concept of APD. Efforts made to establish substitutes for some of the popular, but

endangered herbal drugs in international levels are also presented. It reviews the

botanical candidates of 2 sets of APDs shortlisted for scientific studies, i.e., Ativiṣā

(Aconitum heterophyllum Wall. ex. Royle) - Mustā (Cyperus rotundus L.) and Dāḍima

(Punica granatum L.) - Vṛkṣāmla (Garcinia indica Choisy.). It also emphasizes of the

literature on the trans-disciplinary research method which is used in this PhD thesis.

2.2 Methodology

Charaka Samhitā, Suśruta Samhitā, Aṣṭānga Sangraha and Aṣṭānga Hṛdaya - classical,

Ayurvedic encyclopedia of c. 15th Century BCE – 7th Century CE), Chikitsāgranthas

(Ayurvedic texts on pathophysiology and treatment written after 8th century CE ) and

Nighaṇṭus (lexicons of c. 10-16th century CE) were referred to review the concept of

APD in Ayurveda. Published Ayurvedic books, especially on Dravyaguṇa and Bhaiṣajya

Kalpanā, Ayurvedic Pharmacopoeia of India (API) and Formularies and articles in peer

reviewed journals on APD concept were also referred. The published books and literature

on the information about the habit, habitat, trade, phytochemistry and pharmacology of

the selected four plant species were obtained from the databases like PubMed and

SciFinder. The concepts of trans-disciplinary research were obtained from the published

literature in peer reviewed journals.

2.3 Relevance of APD concept

Contemporary herbal drug industry is facing problems of inadequate supply of crude

herbs for several reasons, prompting illegitimate or un-researched substitution and

adulteration. Meanwhile, over exploitation of threatened species to serve the demand

builds immense pressure on biological diversity (Ved and Goraya, 2008). Providing


16

effective and safe substitution for unavailable drugs is the need of the day. Concept of

drug substitution is not new to Ayurveda and has been mentioned from Samhitā period

(1500 BCE) up to the Modern period (19th century CE). Several examples of unavailable

(AD) and substitutes (APD) have been mentioned in classical texts of Ayurveda (Misra,

2002; Mishra, 2007; Sastry, 2002). Unavailability of the original drug due to geographical

and/or seasonal variations would have led to substitution. Biodiversity and habitat loss

due to over-exploitation of some medicinal plant species and expanding human

population may have also pushed several species to near extinction and urged the need

for substitution. However, without valid reasoning, for the modern scientists not familiar

with Ayurveda as well as contemporary Ayurvedic practitioners, the substitution may

appear non-scientific, raising questions about the propriety of their use in treatment

(Nagarajan et al., 2015).

2.3.1 Need to select APDs

Bhaiṣajya Ratnāvalī gives an indication to go for APDs:

Kadāchit dravyamekam vā yoge yatra na labhyate | Tatguṇayuktam dravyam parivṛtena

grhyate || (Bhaiṣajya Ratnāvalī, Abhāva Prakaraṇa, 1)

Whenever a medicinal drug/ingredient in a formulation is not available, it is advised to

take another drug with similar guṇa (properties) (Mishra, 2007).

In addition to this, Bhāvaprakāśa says, ‘Anuktamapi yuktam yadyojayettadrasādivit’

(Bhāvaprakāśa, Miśrakaprakaraṇa, 166).

A material can be selected, even if it is not mentioned in a group of drugs indicated for

the treatment of a particular disease, provided, it has similar rasa etc. to that of the

drugs in the group. He has also mentioned the necessity of use of substitutes for the rare

drugs in Aṣṭavarga group (section 1.5.2) (Chunekar, 2004; Misra, 2002).


17

2.3.2 APD concept in traditional knowledge

Charaka Samhitā theoretically approves the usage of APDs (Sastry, 1997a). Roots of

Eraṇḍa are indicated by Suśruta Samhitā and its commentator Dalhana instead Gokṣura

in the context of laghupanchamūla (Suśruta Samhitā, Sūtra Sthāna, 38/66) (Acharya,

1992). This has been supported by later written texts like Siddhasara Samhita (Ghildhiyal

et al., 2013). It was Bhāva Miśra, the medieval period Nighaṇtu writer, who stressed on

the need for APDs and suggested several APD herbs (Chunekar, 2004). Later, in the

modern era, Chikitsāgranthas like Bhaiṣajya Ratnāvalī (Mishra, 2007), Yogaratnākara

(Sastry, 2002), Chikitsāsāra Sangraha (Saxena, 2004) and Ayurveda Saukhyam (Dash,

1997) and regional language books like Vaidya Chintāmaṇi (Sarma, 1996) and

Swayamvaidya (Tiruka, 1991) mentioned APDs for several ADs. Apart from the codified

knowledge, living traditions also holds knowledge of APDs. Traditional practitioners found

to use APDs in several instances.

Kauṭilya in his Arthaśāstra documents that, substitution/adulteration of plant drugs

because of their high demand in trade (Krayavikraya) (Shamasastry, 2014). Substitution

of raw drugs is a common practice in Indian raw drug market. However the process of

substitute identification and reasons for using a particular substitute are not detailed in

the Ayurvedic texts (Nagarajan et al., 2015).

A list of fully referred AD-APD pairs in codified systems and living traditions and an

analysis of similarities and differences between the selected AD-APD pairs has been

provided in chapters 4 and 5.


18

2.4 Research on the concept of APD

With rising concern for conservation of endangered medicinal species, serious attempts

are underway in different parts of the globe to find substitute herbs for endangered

ones. In India, AFI has approved some substitutes (AFI, 2000; AFI, 2003) (Section 2.4.1)

and Ayurvedic industry uses substitutes for several drugs, but the similarity in the

bioactivity of suggested substitute with the original drug has not been scientifically

established. The Ayurvedic concept of herbal drug substitution has not been explored by

scientists and by Ayurvedic scholars alike.

Some drug pairs (of unavailable and substitute) have been studied by scientists in stray

instances, but no effort has been made to understand the logic of substitution and to

bring it up to the level of formularies. A list of Ayurveda suggested APDs along with

preliminary yet systematic attempts to relate the APDs as in the case of Ativiṣā (A.

heterophyllum) and Mustā (C. rotundus) was the first report on APDs in contemporary

literature. It reports similarities not only at the level of Ayurvedic understanding, but also

in terms of phytochemical profiles and selected pharmacological actions

(Venkatasubramanian et al., 2010) of Ativiṣā and Mustā. Similar is the case with Vidārī

(Pueraria tuberosa) and Kṣīra Vidārī (Ipomoea mauritiana) (Venkatasubramanian et al.,

2009). Subsequently, some publications have discussed about this concept. A review by

Joshi and Patel (2012) mentions the possibility of adoption of APD concept in

contemporary situations. They have shown the relevance of substitution practices, like

the substitutes for Bṛhatī (Solanum indicum Linn.) which are not classically indicated

(Joshi and Patel, 2012). A review by Giri (2014) states the possible role of APD concept

in quality medicinal products and conservation of medicinal plants. They also urge the

need for re-validation of documented APDs in Ayurvedic literature and practiced by the

Ayurvedic Vaidyas (Giri, 2014).


19

Substitution at the practice level, without a specified Ayurvedic logic was also scrutinized

for understanding the basis and validity of APD. Fruits of different species like Embelia

tsjeriam-cottam A.DC., Maesa indica (Roxb.) A.DC. and Myrsine africana L. sold in the

name of Viḍanga (Embelia ribes Burm. F.) showed similar bio-activity in terms of their

anthelmintic potential (Venkatasubramanian et al., 2013). However their chemical

profiles were not similar (Kuruvilla et al., 2010).

Some other candidates like Saraca asoca De wilde. are found to be substituted with

different species. Attempts have been made to relate the phytochemical and

chromatographic profiles of the original drug Saraca asoca with substitute drugs Saraca

declinata L. and Polyalthia longifolia Benth. Though some similarities between these

species have been observed, substantial pharmacological evidence has not been found to

consider them as substitutes (Khatoon et al., 2009).

Dāruharidrā (Berberis aristata DC.) is one of the species in high demand, but red listed

medicinal plants. Berberis asiatica Roxb., one of the substitutes for B. aristata indicated

by AFI has been proved to be legitimate, especially as an ingredient in the preparation of

hepatoprotective drugs (Andola and Purohit 2012). Systematic studies have been taken

up to study the Ayurvedic suggestion of Bṛhat Gokṣura (Pedalium murex L.) as a

substitute for Gokṣura (Tribulus terrestris L.), where the researchers observed

phytochemical and some pharmacological similarities between the pair (Renuka et al.

2012; Chandrika et al., 2012). The controversies regarding Aṣṭavarga group of herbs and

their substitution with other herbs have been studied by some of the experts in India

(Sharma and Balkrishan, 2008).

Substitution of medicinal plants is practised at international levels as well. Some attempts

were made to show the scientific relevance of such practices. Zschocke and Staden


20

(2000) have reported the scarcity of Ocotea bullata (Burch.), an important medicinal

plant in South Africa. Their studies have shown that the abundantly available Cryptocarya

species could be its potential substitute in terms of cyclooxygenase-1 and -2 inhibition

activities (Zschocke and Staden, 2000). Root of Pelargonium sidoides, a plant in high

demand exported from Africa experienced a drastic drop in the population. A study

conducted by Lewu et al. (2006) has shown that the leaves of Pelargonium sidoides can

be used as substitute for its roots in the treatment of bacterial infections (Lewu et al.

2006).

2.4.1 Substitutes mentioned in Ayurvedic Formularies of India (AFI)

The Ayurvedic Formulary of India (AFI, Part 1 and 2) provides substitute species for

several plant drugs (Table 2.1) (AFI, 2000; AFI, 2003). Several substitutes in list have

been widely practiced in contemporary herbal drug market. Some of them have been

proved to be legitimate by scientific studies. E.g., Embelia robusta C.B.Clarke. (Syn. E.

tsjeriam-cottam (Roem. & Schult.) A. DC.) is a common substitute of Embelia ribes

Burm.f. and sold as Viḍanga. Venkatasubramanian and co workers (2013) proved the

comparable efficacy of substitute as an anthelmintic herbal medicine. They also have

examined the efficacy of two more market substitutes of E. ribes, namely Myrsine

africana L. (MA) and Maesa indica (Roxb.) DC. (Venkatasubramanian et al., 2013).

Some of the substitutes mentioned by AFI appear to be influenced by variations in

regional practices. E.g., Bergenia ligulata (Wall.) Engl. is used as Pāṣāṇabheda, to

manage urolithiasis. In South India, especially in the state of Kerala and surroundings

Aerva lanata Juss. is used for the same purpose (Sarin, 2008). AFI recognizes the former

plant as authentic species and the other as substitute for Pāṣāṇabheda (Anonymous,

2000; Anonymous, 2003).


21

AFI has cited APDs mentioned in classical Ayurvedic texts only for rare Aṣṭavarga drugs

and not for any of the other ADs. E.g., For Medā (Polygonatum cirrhifolium Royle), it

suggests Asparagus racemosus Willd. as a substitute (Anonymous, 2000). A. racemosus

is Śatāvarī, an APD indicated by Bāvamiśra for both Medā and Mahāmedā (Chunekar,

2004). The other APDs given in the AFI are probably based on regional practice. The

methodology and supporting documents for recommending the APDs are also not

indicated in AFI.

Table 2.1: Substitutes mentioned in AFI, Parts 1 and 2

Sl.

No

Sanskrit name Authentic species Substitute/s (Anonymous,

2000; Anonymous, 2003)

1. Agnimantha Premna integrifolia Linn. Clerodendrum phlomidis Linn. f.,

Premna mucronata Roxb.

2. Amlavetasa Garcinia pedunculata

Roxb.

Rheum emodi Wall

3. Arka Calotropis procera (Ait)

R.Br

Calotropis gigantia (Linn.)

R.Br.ex Ait

4. Asphoṭa Vallaris heynei Spreng. Hemidesmus indicus R.Br.

5. Aśvakarṇa Dipterocarpus alatus

Roxb.

Terminalia tomentosa W.&A.

6. Ajamoda Apium graveolens (Linn.) Trachiospermum roxburghianum

(DC) Sprague

7. Bhārngī Clerodendrum serratum

(Linn) Moen.

Clerodendrum indicum (Linn)

Ktze.

8. Chaṇḍa

(Chorakabheda)

Angelica archangelica

Linn.

Angelica glauca Edgw.

9. Dāruharidrā Berberis aristata DC Berberis asiatica Roxb.ex.D.C/

Berberis lyceum Royle.

10. Dhānvayāsa Fagonia cretica Linn. Alhagi pseudalhagi (Bieb)Desv.

11. Dhattūra Datura metel Linn. Datura inoxia Mill.; Datura

stramonium Linn.

12. Dravantī Jatropha glandulifera

Roxb.

Croton tiglium Linn.

13. Dugdhikā Euphoria thymifolia Linn. Euphorbia prostrata W.Ait

14. Elāvāluka Prunus cerasus Linn. Prunus avium Linn.

15. Jīvaka Microstylis musifera

ridley.

Pueraria tuberosa D.C.

16. Kākolī Lilium polyphyllum D.Don Withania somnifera Dunal.

17. Ksīrakākolī Fritillaria roylei Hook. Withania somnifera Dunal.

18. Lāmajjaka Cymbopogon jwarancusa

Schult.

Vetiveria zizanioides (L) Nash

19. Madayantī Lawsonia inermis Linn. Jasminum sambac Ait.


22

20. Mahāmedā Polygonatum cirrhifolium

Royle

Asparagus racemosus Willd.

21. Murā Selinium tenuifolium Wall. Nardostachys jatamansi D.C.

22. Mūrvā Marsdenia tenacissima

Weight and Arn.

Chonemorpha macrophylla

23. Mustā Cyperus rotundus Linn. Cyperus scariosus R.Br.; Cyperus

adundinaceum Baker

24. Nirviṣa Delphinium denudatum Kyllinga triceps roxb.

25. Pāṣāṇabheda Bergenia ligulata (Wall.)

Engl.

Aerva lanata Juss.

26. Priyangu Callicarpa macrophylla

Vahl.

Prunus mahaleb Linn.

27. Raktapunarnava Boerhavia diffusa Linn. Boerhavia repens Linn.;

Boerhavia rependa Willd.

28. Rāla/śāla Shorea robusta Gaertn. F. Vateria indica Linn.

29. Rāsnā Pluchea lanceolata

Oliver&Hiern.

Alpinia galangal Willd.

30. Reṇuka Vitex agnus-castus Linn. Vitex negundo Linn.

31. Rddhi Habenaria intermedia

D.Don

Dioscoria bulbifera Linn.

32. Rohiśa Cymbopogon martinii

(Roxb.)Wats.

Cymbopogon schoenanthus (L)

Sperng.

33. Rohitaka Tecomella undulata

(G.Don) Seem.

Aphanamixis polystachya (Wall)

Parker.

34. Somavallī Sarcostemma brevistigma

W.A.

Ephedra gerardiana Wall.

35. Spṛkka Anisomeles malabarica

(Linn.) R.Br.

Schizachyrium exile Stapf.;

Delphinium zalil Aitch&Hemsl.

36. Sṛuvavṛkṣa Flacourtia indica Merr. Gymnosporia spinosa (Forsk)

Fiori.

37. Svarṇakṣīrī Euphorbia thomsoniana

Bioss.

Argemone Mexicana Linn.

38. Tālīsa Abies webbiana Lindl. Abies pindrow Spach.; Taxus

baccata Linn.

39. Tuvaraka Hydnocarpus laurifolia

(Dennst.) Sleumer

Hydnocarpus kurzi (King) Wab.

40. Viḍanga Embelia ribes Burm.f. Embelia robusta C.B.Clarke.

41. Medā Polygonatum cirrhifolium

Royle

Asparagus racemosus Willd.

42. Vṛddhi Habenaria intermedia

D.Don.

Dioscoria bulbifera Linn.


23

2.5 Literature review of ADs and APD’s shortlisted for scientific studies

Two sets of AD-APDs were analysed for the scientific validity of substitution. They are

Ativiṣā-Mustā and Dāḍima-Vṛkṣāmla. A brief review of published literature about these

species is given below.

Mustā has been suggested as the APD for Ativiṣā by Bhāvaprakāśa (Misra, 2002),

Yogaratnākara (Sastry, 2004) and Bhaiṣajya Ratnāvalī (Mishra, 2007). Vṛkṣāmla has been

advised as APD for Dāḍima by Bhaiṣajya Ratnāvalī (Mishra, 2007) and Chikitsāsāra

Sangraha (Saxena, 2004).

2.5.1 Ativiṣā

The Ayurvedic Formulary of India identifies Ativiṣā as Aconitum heterophyllum Wall. ex.

Royle (Ranunculaceae) (AFI, 2003).

2.5.1.1 Introduction to A. heterophyllum

More than 300 species are known in the Aconitum family (Been, 1992). A. napellus, A.

chasmanthum, A. ferox, A. palmatum and A. heterophyllum are commonly used

Aconitum species in Indian and Chinese medicine (Chopra and Chopra, 2006; Singhuber,

2009). A. heterophyllum is a perennial herb commonly found in the alpine and sub-alpine

regions above 3000 m. (Sarin, 2008; Nautiyal and Nautiyal, 2004). It has greenish-blue

coloured and helmet-shaped flowers (Fig. 2.1). The roots harvested from plants older

than 2 years are used for medicinal purposes. The tubers generally occur as a pair of

mother and daughter tubers (Fig. 6.1). In India, this species is naturally spread over

Jammu & Kashmir, Himachal Pradesh and in Uttarakhand (Srivastava et al., 2010).

Because of its endangered status, the export of plant portions and derivatives of A.

heterophyllum obtained from the wild is prohibited by the Director General of Foreign


24

Trade (Zoo rules 1992). Cultivation of Ativiṣā has been attempted by both Government

and Non-government agencies in Uttarakhand as a resource augmentation effort

(Nautiyal and Nautiyal, 2004). The annual consumption of Ativiṣā in India is estimated to

be around 200-500 tonnes/year with the price varying from Rs. 2000-4000/kg (Ved and

Goraya, 2008).

Figure 2.1: Habit of A. hetrophyllum


25

2.5.1.2 Phytochemistry of A. heterophyllum

Atisine is the main alkaloid in A. heterophyllum (Chatterjee and Prakash, 1994). It is non-

toxic and therefore, A. heterophyllum is a safer herb to use than other Aconitum species

(Sastry, 2005a). The process of shodhana (purification) is not mandatory for A.

heterophyllum.

Alkaloids: Alkaloids of A. heterophyllum were documented as early as the last decades

of the 19th Century (Jowett, 1896). Atisine was isolated and its molecular formula was

deduced by Broughton (Figure 2.2). Jowett and co-workers investigated the properties

and composition of atisine and its salts (Jowett, 1896). Alkaloids like hetisine,

heteratisine (Figure 2.2) and benzoylheteratisine were isolated by Jacobs and Craig

(1942). The chemical structures of hetisine, atisine and heteratisine were elucidated by

Pelletier and co-workers (Solo and Pelletier, 1962; Pelletier and Parthasarathy, 1965;

Aneja et al., 1973;). They have also isolated and elucidated the structures of diterpene

alkaloids: atidine, atisenol, F-dihydroatisine, hetidine and hetisone, isoatisine; lactone

alkaloids heterophyllisine, heterophylline and heterophyllidine; an entatisene diterpenoid

lactone, atisenol (Pelletier and Aneja, 1967; Pelletier et al., 1968; Pelletier and Ateya,

1982). Two aconitine-type norditerpenoid alkaloids, 6-dehydroacetylsepaconitine and 13-

hydroxylappaconitine were recently reported (Ahmad et al., 2008).

The aconitine content of A. heterophyllum was found to be 0.13 -0.75% (dry weight

basis), based on HPLC studies (Bahuguna et al., 2000; Pandey et al., 2008). Higher

quantities of atisine (0.35%) and aconitine (0.27%) (Figure 2.2) were reported in green

house grown A. hetrophyllum when compared to the naturally grown plants (0.19% and

0.16%, respectively) (Bahuguna et al., 2013). Another study reported 0.0014-0.0018%

aconitine from tubers of A. heterophyllum from the Kashmir valley (Jabeen et al., 2011).

Alkaloids are the main focus of study in A. heterophyllum and several pharmacological

actions of Ativiṣā have been attributed to them.


26

Figure 2.2: Important phytoconstituents of A. heterophyllum

2.5.1.3 Pharmacology of A. heterophyllum

Members of Aconitum species (A. napellus, A. chasmanthum, A. ferox, A. palmatum and

A. heterophyllum) are used in Ayurveda and Chinese systems of medicine (Ukani et al.,

1996). The drug finds common use in the treatment of fevers, diarrhea, indigestion,

inflammation, helminthiasis, hyperlipidemia and as an anti-emetic in children (API,

2001a; Kirtikar and Basu, 1993a). Similar uses for A. heterophyllum are also found in

Unani and Siddha systems of medicines as well (Anonymous, 1993; Kirtikar and Basu,

1993a).

Antihyperlipidemic activity: The methanolic extract of tubers of Ativiṣa (A.

heterophyllum) decreased total cholesterol, LDL-c, triglycerides and apolipoprotein B in

blood serum diet induced obese rats. It decreased intestinal fat absorption also. Whereas

OCH3

OH

OCH3

OCH3

HO

NC2H5

OH

H3CO

O

C

O CH3

O

C

O

Aconitine (C34H47NO11)

CH2

N

CH3

H

H

OH

O

Iso-Atisine (C22H33NO2)

N

CH3

OCH3

O

O

OH

HO

Heteratisine (C22H33NO5)

CH3

CH2

O

O

OH

H

Atisenol (C20H28O3)

CH2

OH

H

N

CH3

H

H

O

Atisine (C22H33NO2)

http://www.chemspider.com/Molecular-Formula/C22H33NO2




27

in rodents there was an increase in HDL-c and apolipoprotein A. Inhibition of

hydroxymethylglutarate- coenzyme A reductase (HMGR) and activation of Lecithin-

cholesterol acyltransferase (LCAT) was considerd to be reason for antilipidemic activities

(Subash and Augustine, 2012).

Anti-inflammatory and antipyretic activity: Ethanolic extracts of A. heterophyllum

showed anti-inflammatory activity in the cotton pellet induced granuloma test (Verma et

al., 2010). Antipyretic effects of its aqueous, chloroform and hexane extracts were seen

in rats with yeast induced pyrexia (Ikram et al., 1987).

Action on the nervous system: A. heterophyllum makes the sympathetic nervous

system more sensitive to physiological stimuli. Atisine has a hypotensive effect, but the

whole plant extract has hypertensive properties. Hypertension produced by high doses of

aqueous extract may be because of the excitement of the sympathetic nervous system

(Raymond-Hamet, 1938; Raymond-Hamet, 1954). Diterpenoid alkaloids heterophyllinines

A and B, were about 13 times more selective in inhibiting the enzyme

butyrylcholinesterase than acetylcholinesterase. These enzymes are involved in the

transmission of nerve impulses (Nisar et al., 2009).

Antibacterial activity: Aconitine type nor-diterpenoid alkaloids 6-

dehydroacetylsepaconitine and 13-hydroxylappaconitine, isolated from the tubers of A.

heterophyllum along with the known alkaloids lycoctonine, delphatine and lappaconitine,

displayed antibacterial activity against gram negative (diarrhea causing) bacteria

Escherichia coli, Shigella flexineri, Pseudomonas aeruginosa and Salmonella typhi

(Ahmad et al., 2008).


28

Anthelminthic activity: Aqueous and alcoholic extracts of tubers of A. heterophyllum

had significant activity against Pheritema postuma (earthworm), compared to standard

piperazine citrate (Pattewar et al., 2012).

Immunomodulatory activity: The immunomodulatory activity of the ethanolic extract

of A. heterophyllum was exhibited in terms of delayed type hypersensitivity, humoral

responses to sheep red blood cells, skin allograft rejection and phagocytic activity of the

reticuloendothelial system in mice. It enhanced phagocytic function and inhibited the

humoral component of the immune system (Atal et al., 1986).

2.5.2 Mustā

Mustā has been recognized as Cyperus rotundus L. (Cyperaceae) by AFI (AFI, 2003).

2.5.2.1 Introduction to C. rotundus

C. rotundus, also known as purple nutsedge or nutgrass, is a common weed found all

over India in fields, agricultural land and moist waste land (Sarin, 2008). It is a tufted,

grass-like perennial plant, whose stem is three angled at the top with brown spikelets.

Inflorescences are small, consisting of tiny flowers with a red-brown husk (Fig. 2.3).

Rhizomes are 3-20mm in diameter, rust-coloured turning black (Fig. 6.2) with a

characteristic odour. The rhizomes from 2 year old plants are used for medicinal

purposes. Consumption of Mustā is estimated to be 2000-5000 tonnes per year with a

cost range of Rs.15-30/kg. (Ved and Goraya, 2008).

2.5.2.2 Phytochemistry of C. rotundus

Terpenoids are the major phytoconstituents in C. rotundus. Phenolics and flavonoids are

also present (Meena et al., 2010) and there is only one report on the occurrence of

alkaloids in C. rotundus (Jeong et al., 2000).


29

Figure 2.3: A plant of C. rotundus

Terpenes: Cyperene, a sesquiterpene, cyperene, was isolated from the essential oils of

C. rotundus (Trivedi et al. 1964). A ketone, mustākone (Fig. 2.4), copadiene (a

conjugated diene), epoxyguaiene (an epoxide), rotundone and α-cyperone (Figure 2.4),

cyperolone (a hydroxy ketone) were found in C. rotundus (Kapadia et al., 1965). The

isolation and structure elucidation of rotundene and rotundenol (sesquiterpenoids) were

reported by Paknikar et al., 1977. Triterpenoid acid oleanolic acid and its glycoside was

isolated from the benzene extract of C. rotundus. (Singh and Singh 1980). The presence

of caryophyllene in C. rotundus was also reported (Dhillon et al., 1993). The chemical

constituents responsible the anti-malarial activity of C. rotundus were recognized as


30

patchoulenone, caryophyllene alpha-oxide, 4, 7-dimethyl-1-tetralone and sesquiterpene

endoperoxide 10, 12-peroxycalamenene (Thebtaranonth et al., 1995).

Several sesquiterpenoids (Ohira et al., 1998), patchoulane type sesquiterpenes and

eudesmane types and nortriterpenoids were isolated from the rhizomes of C. rotundus

(Kim et al., 2012; Yang and Shi, 2012).

Glycosides: C. rotundus rhizomes were contained iridoid glycosides, rotundusides A and

B (Zhou and Zhang, 2013; Zhou et al., 2013). A Keto-alcohol, triterpenoid glycosides, 18-

epi-alpha-amyrin glucuronoside and oleanolic acid arabinoside were also reported (Alam

et al., 2012).

Tannins, flavanoids and coumarins were found to be present in all various extracts of C.

rotundus. The essential oil showed the presence of around 70 sesquiterpene

hydrocarbons along with oxygenated sesquiterpenes and a few monoterpene

hydrocarbons (Kilani et al., 2007). Norsesquiterpene norcyperone (Xu et al., 2008),

Epiguaidiol A and sugebiol, guaidiol, sugetriol triacetate, cyperenoic acid and

cyperotundone (Xu et al., 2009), sesquiterpenoids – rotundusolide A & B and

rotundusolide C were also reported (Yang and Shi, 2012).

Phenolics and flavonoids: The ethanolic extract of C. rotundus was reported contain

73.27± 4.26 g/100g of phenolic content (catechin equivalents) (Nagulendran, 2007).

Phenolics and flavonoids- quercetin, kaempferol, catechin and myrcetin (Samariya and

Sarin, 2013), luteolin, ginkgetin and isoginkgetin (Zhou and Fu, 2013) and phenolics

were also reported from C. rotundus (Zhou and Yin, 2012).

Alkaloids of C. rotundus: Jeong and co-workers (2000) reported 3 sesquiterpene

alkaloids from the rhizomes of C. rotundus, Rotundines A-C (Fig. 2.4) in small quantities

(0.7-1.1 ppm) (Jeong et al., 2000). Recently, a complex mixture of terpenoids and

alkaloids and condensed tannins in the rhizomes of C. rotundus, was observed during

histochemical studies on C. rotundus (Adams et al., 2013).


31

Figure 2.4 Important Phytoconstituents of C. rotundus

Chemotypes of C. rotundus: Based on the composition of essential oils, 4 chemotypes

of C. rotundus have been reported. They are, H, M and O (found in Asia), K (common in

Hawaiian islands). Type O is most widely distributed. (Komai et al., 1991).

The composition of the essential oil of C. rotundus shows geographical variation. The

essential oils of C. rotundus from South India were found to have the dominance of α-

copaene (11.4%), valerenal (9.8%), caryophyllene oxide (9.7%), cyperene (8.4%),

nootkatone (Figure 2.4) (6.7%), and trans- pinocarveol (5.2%) (Jirovetz et al., 2004).

Whereas the samples from Dehradun showed 5-oxo-isolongifolene (16.27%), α-

gurjunene (10.22%), valerenyl acetate 8.88%) α-salinene (4.48%), valerenic acid

(3.67%) and γ-cadinene(3.4%) as the major components (Bisht et al., 2011).

N

X=

6

X

OHHX = , , epimeric at C-6, Rotundines B & C

O, Rotundine A

Alkaloids of Cyperus rotundus

O

Mustākone (C15H22O)

O

α-Cyperone (C15H22O)

Nootkatone (C15H22O)

http://www.chemspider.com/Molecular-Formula/C15H22O


32

2.5.2.3 Pharmacology of C. rotundus

C. rotundus is used extensively in the management of fevers, diarrhoea, thirst,

inflammation, tastelessness, helminthiasis, indigestion and obesity in traditional Indian

medicine (Kirtikar and Basu, 1993b). Similar uses for C. rotundus are found in the Siddha

system as well (Anonymous, 1993).

Anti-obesity and anti-hyperlipidemic activity: In obese Zucker rats the hexane

extracts of C. rotundus rhizomes reduced weight gain by 10%, which was reasoned as

due to activation of the β3-AR (adrenoreceptor) (Lemaure et al., 2007). In another

study, the aqueous and alcoholic extracts lowered total cholesterol, triglyceride and low

density lipoprotein levels in serum in rats (Chandratre et al., 2011; Chandratre et al.,

2012).

Hypoglycemic activity: The hydro-alcoholic extract of C. rotundus rhizomes at

500mg/kg was as effective as metformin at 450mg/kg in reducing glucose levels in

alloxan induced hyperglycemic rats (Raut et al., 2006). It was proved to be capable of

inhibiting protein glycation, alpha-glucosidase and alpha-amylase (Ardestani and

Yazdanparast, 2007). A flavane, (2RS, 3SR)-3,4’,5,6,7,8-hexahydroxyflavane and the

stilbene dimers cassigerol E and scirpusins A and B were found to be responsible for this

activity (Thi et al., 2014).

Anti-diarrhoeal activity: The methanolic extract of C. rotundus had significant

antidiarrhoeal activity compared to loperamide (Uddin et al., 2006). The aqueous

decoction of C. rotundus rhizome showed significant inhibition of labile toxin and stable

toxin production of 2 groups of E. coli, EPEC (enteropathogenic) and ETEC

(enterotoxigenic). C. rotundus had limited antibacterial/anti-rotaviral activity. Mustā’s anti

diarrhoeal effect was attributed to action on some feature of bacterial virulence such as


33

colonization, production of cholera toxin or labile toxin rather than killing the bacteria

(Birdi et al., 2011; Daswani et al., 2001).

Anti-inflammatory activity: C. rotundus essential oil was proved to have anti-

inflammatory, anti-arthritic, analgesic and anti-convulsant effect when studied using in

vitro and in vivo models (Biradar et al., 2010; Tsoyi et al., 2011, Kim et al., 2013, Jung et

al., 2013). The anti-inflammatory, analgesic and anti-genotoxic activity were attributed to

the flavonoids, tannins and polyphenols of C. rotundus (Soumaya et al., 2013)

Anti-microbial activity: Several reports state that C. rotundus has anti-microbial

activity. Its essential oil was active against gram positive micro-organisms (El-Gohary et

al., 2004). The hexane and water extracts were showed inhibition against B. pumilis (Sini

and Malathy, 2005). It suppressed Streptococcus mutans and the production of organic

acids by the same bacteria, thus proving it as an anticariogenic agent (Yu et al., 2007). It

has also showed various levels of antibacterial effect against Staphylococcus aureus,

Enterococcus faecalis, Escherichia coli, Salmonella enteritidis, and Salmonella

typhimurium, Bacillus subtilis, Enterococcus faecalis, Salmonella enteridis and Salmonella

typhimurium (Kilani et al., 2007; Bisht et al., 2011; Kilani-Jaziri et al., 2011). Significant

antifungal activity of C. rotundus compared to the standard drugs was observed against

C. parapsilosis and A. fumigates, F. oxysporum and A. flavus (Bisht et al., 2011), Candida

albicans and Aspergillus niger (Biradar et al., 2010).

Anthelmintic activity and Cytotoxic activity: Essential oil of C. rotundus has

showed anthelmintic activity against Pheretima postuma and Ascardia galli (Biradar et al.,

2010). The essential oil of C. rotundus rhizomes showed positive result against Ehrlich

ascites carcinoma cells with 100% inhibition, but not against human tumor cell lines (El-

Gohary et al., 2004).


34

CNS activity: Ethanolic extract of C. rotundus rhizome showed CNS depressant activity..

It enhanced sleeping time, had analgesic and anticonvulsant activities and reduced

different behavioral reflexes (Pal et al., 2009). The total oligomeric flavanoids (TOFs)

obtained from rhizomes of C. rotundus had neuroprotective effects. It helped to relieve

oxidative stress and improved neurological behavioral alterations in rats subjected to

middle cerebral artery occlusion and reperfusion (Sunil et al., 2009). Neuroprotective

function of Mustā was also proved by in vitro studies also (Kandikattu et al., 2013;

Kumar and Khanum, 2013).

Antioxidant activity: Studies proved that, C. rotundus is a potent antioxidant herbal

drug. Its hydro-alcoholic, ethyl acetate extracts exhibited free radical scavenging,

reducing power, antimutagenic, radical scavenging and antigenotoxic and metal chelating

activities (Kilani et al., 2007; Nagulendran et al., 2007). It was also proved to have anti-

cataract activity (Seema et al., 2007). Extracts of Mustā inhibited xanthine oxidase,

superoxide anion and protected against hydrogen peroxide/UV induced DNA damage.

The extract exerted antiproliferative effect towards K 562 erythroleukemia cells (Kilani-

Jaziri et al., 2009). The rhizomes had anti-oxidant activity in DPPH assay and inhibition of

linoleic acid lipid peroxidation (Pal and Dutta, 2006; Bashir et al., 2012). A significant

decrease in mucosal damage was reported on administration of C. rotundus, suggesting

its free radical scavenging activity (Guldur et al., 2010). Extracts of the aerial parts of C.

rotundus also reduced genotoxicity induced by nifuroxazide and aflatoxin B1 (Kilani-Jaziri

et al., 2011).

Anti-allergic activity: The anti allergic activity of C. rotundus was proved by both in

vitro and in vivo studies. Its sesquiterpenes inhibited release of histamines and 5– LOX


35

(lipoxygenase) enzyme. The ethanol extracts and isolated sesquiterpenes, monoterpenes

& 4-cymene were found to be effective. (Jin et al., 2011).

Antiplatelet activity: The ethanolic extract of C. rotundus and nootkatone were

capable of inhibiting platelet aggregation, which was confirmed by in vivo studies in rats,

prolonging the bleeding time. (Seo et al 2011).

Insecticidal and plasmodicidal activity: C. rotundus was active against “Asian tiger

mosquito” (Kempraj and Bhat, 2008) and three other mosquito species, which shows its

role as insecticidal agent (Singh et al., 2009). C. rotundus hexane extract was active

against Plasmodium falciparum (Thebtaranonth et al., 1995) as well as German

cockroach (Blatella germanica L.) (Chnag et al., 2012).


36

2.5.3 Dadima

Dāḍima has been recognized as Punica granatum L. (Punicaceae) (AFI, 2003).

2.5.3.1 Introduction to P. granatum

Dāḍima (P. granatum) is a glabrous small tree, growing up to a height of 3 m. It is native

to Iran and extensively cultivated in China, Northern India, California, and Mediterranean

region (Rahimi et al., 2012). Leaves are opposite or sub-opposite; obovate or oblong.

Flowers are terminal or axillary, scarlet or orange-red coloured. Fruits are either red or

pale greenish depending up on the variety. They are globose and crowned with the limb

of calyx (API, 1999) (Figure 2.5). Edible part is the seeds/arils, which are angular and

coriaceous (Figure 5.8). Fruit rinds are also used in management of indigestion related

diseases (Sharma, 2006b).

Figure 2.5 Fruits of P. granatum


37

2.5.3.2 Phytochemistry of P. granatum

Tannins: P. granatum has hydrolysable tannins like ellagitanins and gallotanins as major

components. They are found in different parts of the plant. Though several tannins are

reported from different parts of P. granatum tree, gallic acid and ellagic acid (Figure 2.6)

are the major tannins isolated from the juice (Wang et al., 2010).

Leaves contain tannins like brevifolin, brevifolin carboxylic acid, ethyl

brevifolincarboxylate, corilagin, ellagic acid, gallic acid (figure 2.6), β-D-glucose,

punicafolin, strictinin, tercatain, 5-O-galloyl-punicacortein D. The peel contains 2,3-(S)-

HHDP-D-glucose, granatin B. Bark is rich in castalagin, casuariin, casuarinin,

punicacortein A and B, punicacortein C, punicacortein D, punicalin and punicalagin

(Rahimi et al., 2012)

Flavonoids: Flavones, flavanols, anthocyanidins and flavan-3-ols are the common

flavonoids of P. granatum. Major flavonoids present in the juice are catechin, catechol,

cyanidin-3-glucoside, cyanidin-3,5-diglucoside, cyanidin-3-rutinoside, delphinidin-3-

glucoside, delphinidin 3, 5-diglucoside, pelargonidin 3-glucoside, pelargonidin 3,5-

diglucoside, epicatechin, epigallocatechin-o-gallate, flavan-3-ol, quercitin and epiquercitin

(Rahimi et al., 2012). The brilliant red colour of pericarp and juice is attributed to

anthocyanidins and flavan-3-ols, which greatly vary during the stages of maturity of the

fruits. Anthocyanidins of pomegranate are in the form of glycosides with the aglycons of

delphinidin, cyaniding and pelargonidin. (Wang et al., 2010).

Alkaloids: Though the juice contains some alkaloids, they are mainly found in the stem

and root. They are of two types, piperidines and pyrrolidines (Wang et al., 2010).

Tryptamine, serotonin and melatonin are mainly found in the juice. Peelletierine, N-

methylpelletierine, pesudopelletierine are commonly found in bark and roots (Neuhofer


38

et al., 1993). Roots and rinds of pomegranate tree have up to 3% and 0.6% of alkaloids

respectively (Mohammad and Kashani, 2012).

Organic acids: Pomegranate juice mainly contains organic acids like citric acid and

malic acid, tartaric acid and oxalic acid (Rahimi et al., 2012).

Terpenes: Triterpenes like ursolic acid, oleolinic acid, punicanolic acid and steroids like

stigmasterol, camesterol and beta- sitosterol are present in pomegranate fruit juice and

rind (Wang et al., 2010).

Ellagic Acid Derivatives: Pomegranate fruit, pericarp and bark contain ellagic acid.

Seeds are rich in 3,3′-di-O-methyl ellagic acid and 3,3′, 4′-tri-O-methyl ellagic acid. The

trees heartwood contains ellagic acid and diellagic acid rhamnosyl(1-4) glucoside (Rahimi

et al., 2011).

Figure 2.6: Important Phytoconstituents of P. grantum

Ellagic acid (C14H6O8)

Gallic acid (C7H6O5)

Brevifolin (C10H12O4)

Corilagin (C27H22O18)


39

2.5.3.3 Nutritional value of pomegranate

Pomegranate is a highly acclaimed fruit having good nutritional value. Table 2.2 provides

the nutritive value of pomegranate.

Table 2.2: Nutritional value of pomegranate fruit (per 100 g of edible pulp) (Adapted

from Garach et al., 2012)

Composition Quantity

Water 80-82 g

Energy 63-68 Kcal

Carbohydrates 16.4 g

Protein 0.5-0.9 g

Fat 0.3-0.9 g

Ash 0.5 g

Phosphorous 8 mg

Iron 0.3 mg

Potassium 259 mg

Calcium 3 mg

Sodium 3 mg

Manganese 3 mg

Zinc 0.12 mg

Magnesium 015 mg

Copper 0.07 mg

Selenium 0.6 mg

Panthothenic acid 0.59 mg

Vitamin B1 0.03 mg

Vitamin B2 0.03 mg

Vitamin B3 0.03 mg

Vitamin C 4-6 mg

2.5.3.4 Pharmacology of P. granatum

In traditional medicine, pomegranate is widely used in the management of heart

diseases, indigestion problems, stomach disorders and anemia. Its rind is used in the

management of dental diseases, diarrhoea and skin diseases (Bhowmik et al., 2013).

Antioxidant activity: The polyphenols and flavonoids in the juice were considered to

control oxidative stress which in turn causes lipid peroxidation in arterial macrophages

and in lipoproteins (Noda et al., 2002). Pomegranate displayed hydroxyl radical and

superoxide anion scavenging activity, which was related to the presence of

anthocyanidins (Guo et al., 2007; Seeram et al., 2006).


40

Anti-inflammatory activity: Pomegranate inhibited cyclooxygenase (COX) and

lipooxygenase (LOX) (Schubert et al., 1999; Rahimi et al., 2011). It was showed to have

ability to manage osteoarthritis by reducing inflammation, as well as by preventing

collagen degeneration (Ahmed et al., 2005). It also controled colitis in rats (Larrosa et

al., 2010).

Anti-cancer activity: Several in vitro and in vivo studies indicate the therapeutic

potential of pomegranate in prostate cancer. Gallic acid and its polyphenols were found

to be responsible for its therapeutic role in cancer (Khodzhaeva et al., 1985; Lansky et al.

2007). In vitro and animal studies by Sturgeon and Ronnenberg (2010) showed that

pomegranate has the capacity to prevent breast cancer. They have explained the

possible mechanisms involved in this action (Sturgeon and Ronnenberg, 2010). One of

the constituents of pomegranate, punicic acid, was capable of inhibiting the proliferation

breast of cancer cell line MDA-MB-231. During the study, apoptosis of cells was also

observed, which was explained to be due to lipid peroxidation of cells and activation of

protein kinase C (PKC) (Grossmann et al., 2010).

Hypertension: Through a clinical trial pomegranate was proved as an antihypertensive

drug along with its ability to inhibit serum angiotensin converting enzyme (ACE). In

patients administered with pomegranate juice, there was about a 5% reduction in

systolic blood pressure (Yurdasheva et al., 1978).

Neuroprotection: Pomegranate juice, especially the polyphenols are known to have a

role in neuroproction. There was a decrease in accumulation of soluble amyloid-beta in

transgenic mice (with Alzheimer’s like pathology) treated with pomegranate juice. Their

memory and learning capacity also improved (Zelepukha et al., 1975).


41

Antimicrobial activity: The methanolic extract of pomegranate peel was an inhibitor of

several microbes including Listeria monocytogenes, Staphylococcus aureus, Escherichia

coli and Yersinia enterocolitica (Julie et al., 2008). It suppressed the growth of

pathogenic clostridia and Staphylococcus aureus (Bialonska et al., 2009). It was also

active against norovirus infections (Su et al., 2010) and influenza virus (Haidari et al.,

2009). The peel extract, especially punicalgin, was active against fungal species

Paracoccidioides brasiliensis, Candida albicans and Candida parapsilosis (Endo et al.,

2010). Sun-dried rind of the immature fruit of P. granatum is used as malaria

prophylaxis. Methanolic extracts of pomegranate inhibited Plasmodium falciparum and

Plasmodium vivax (Dell’Agli et al. 2009)

Glucose and lipid metabolism: Pomegranate flower extract was orally fed to

streptozotocin-induced diabetic rats and potent anti-hyperlipidemic and hypoglycemic

activity was observed (Bagri et al., 2009). It was also seen that pomegranate leaf tannins

modulate the lipid metabolism and act on liver cells (Lan et al. 2009).

Cardiovascular health: Pomegranate is considered to be a cardio protective food. P.

granatum juice and its polyphenol rich extracts had activity against platelet aggregation.

Polyphenol rich extracts showed action against platelet activation (Mattiello et al., 2009).

The rats fed with pomegranate juice were shown to have better cardiac health in terms

of plasma marker enzymes, lipid peroxidation, Ca2+ ATPase, endogenous enzymatic and

non-enzymatic antioxidants compared to the controls (Jadeja et al., 2010).

Skin protection: Pomegrante juice and derived products were effective in preventing

the damage caused by ultra violet rays in human reconstituted skin (EpiDermTM FT-200)

(Afaq et al., 2009)


42

Hepatoprotection: A beverage produced from pomegranate flowers was proved to be

effective to prevent liver damage induced by trichloroacetic acid. In rats treated with

pomegranate juice, lower levels of alanine aminotransferase (ALT), aspartate

aminotransferase (AST), creatine kinase (CK), malonaldehyde contents in liver, brain,

kidney and hearth tissues were seen compared to the controls (Celik et al. 2009)

2.5.4 Vṛkṣāmla

Vṛkṣāmla is Garcinia indica Choisy. (Clusiaceae) (AFI, 2003).

2.5.4.1 Introduction to G. indica

Vṛkṣāmla (G. indica), a member of Mangosteen family is indigenous plant of India. Genus

garcinia has more than 200 species, of which most of them are endemic to South-East

Asia. G. indica is naturally grown and often cultivated in small scale in the humid regions

of Western Ghats in India (Figure 2.7) (Ramachandran, 2014).

Figure 2.7: Habit of G. indica

http://en.wikipedia.org/wiki/Jacques_Denys_Choisy


43

It is a medium sized, evergreen glabrous tree growing up to a height of 20 m. Fruiting

season is April-May. The useful part is its dark red coloured fruit (Figure 2.7) containing

3-4 large seeds, embedded in whitish, sweet-sour pulp and connected to the rind (Pasha

and Ramachandran, 2014).

Fruit rinds (fresh/dried) (Fig. 6.9) are used both in medicinal and culinary preparations. It

is added to curries to give sour taste and red colour. Generally, the fresh fruits are cut

into halves, the pulp and seeds are separated from the rind and the rinds are sun dried

for a week. This primary process gives a longer shelf life to the rinds. Syrup prepared

from the rinds of G. indica is often sweetened, diluted with water used as refreshing cold

drink in summer (Kureel et al., 2009). Seeds yield around 25% fat, known as Kokum

butter, which is used as a topical application in burns and skin diseases, apart from

culinary preparations (Ramachandran, 2014). India produces more than 10,000 metric

tons of Kokum every year (Kureel et al., 2009).

2.5.4.2 Nutritional value of Vṛkṣāmla

G. indica is an acidic fruit, rich in organic acids. Table 2.3 gives the proximate

composition of fresh fruits of Vṛkṣāmla.


44

Table 2.3: Nutritional value of G. indica (per 100 g of fruit) (Kureel et al., 2009;

Parthsarathy and Nandakishore, 2014; Pasha and Ramachandran, 2014)

Composition Quantity

(In fresh fruit rinds)

Water 80 g

Sugars 4.1 g

Protein 1-1.92 g

Fat 1.4 g

Tannins 1.7-2.6 g

Pectin 1-5.7 g

Organic acid 5.9 g

Anthocyanins 2.4 g

Crude fiber 14.28 g

Ash 2.6 g

(In dry rinds)

Iron 12.06mg

Potassium 44.5 mg

Calcium 13.21 mg

Sodium 1.55 mg

Phosporous 0.45 mg

Magnesium 33.45 mg

Vitamin B1 (Thiamin) 52 µg

Vitamin B2 (Riboflavin) 275 µg

Vitamin B3 (Niacin) 45 µg

Vitamin C (Ascorbic acid) 14.35 mg

Vitamin B12 8.75 µg

Total vitamins 14.75 mg

Total acidity 14.11 %

HCA 7.43%

Malic acid 2.67%

Oxalic acid 0.63%

Citric acid 0.79%

Tartaric acid 0.51%

Acetic acid 0.31%

Total phenols 5.01 g

2.5.4.3 Phytochemistry of G. indica

Vṛkṣāmla or Kokum is popular for its organic acids that give characteristic acidic taste

and water soluble anthocyanins that give attractive pink-red colour to the fruits. It also

has garcinol, a polyisoprenylated benzophenone derivative, known for many of the

nutraceutical actions of G. indica. Kokum is valued as it is a rich source of hydroxycitric

acid (HCA), a proven anti lipidemic molecule (Jayaprakasha and Sakariah, 2002). Its

phytochemical analysis showed the presence of terpeniods, alkaloids, saponins,


45

flavanoids, glycosides & carbohydrates, phenolic, tannins and phytosterols (Pasha and

Ramachandran, 2010).

Organic acids: Hydroxycitric acid (1,2 dihydroxypropane-1,2,3-tricarboxylic acid) is the

main organic acid in the rinds of many Garcinia species, and in G. indica as well. This

citric acid derivative is also called as garcinia acid. Rinds usually contain about 7-20 % of

(-)-HCA on dry basis (Fig. 2.8). Low amounts of HCA and HCA-lactone were detected in

Kokum leaves also (Jayaprakasha and Sakariah, 2002). Citric, malic and ascorbic acid are

also present in the rinds. (Pasha and Ramachandran, 2014).

Flavonoids: G. indica has anthocyanin glycosides, polyphenols- a proauthocyanidin and

a biflavanoid. Its anthocyanins give the characteristic red colour to the fruit. It has red

pigments up to 3 %. The pigments are cyanidin-3-glucoside and cyanidin-3-

sambubioside, with sugar association of glucose and xylose, respectively. Red coloured

Garcinia anthocyanins are water soluble. Xanthones, benzophenones, lactones and

phenolic acids are also reported from G. indica (Nayak and Rastogi, 2010).

Figure 2.8: Important Phytoconstituents of G. indica

(-)-Hydroxycitric acid (C6H8O8)

General structure of Anthocyanidins

Garcinol (C38H50O6)


46

Garcinol: G. indica has a yellow pigment called garcinol or camboginol (C38H50O6) up

to 3%. It is basically a polyisoprenylated benzophenone derivative with multiple phenolic

hydroxyl groups (Fig. 2.8) and shows potent antioxidant activity. (Nayak and Rastogi,

2010; Pasha and Ramachandran, 2014).

2.5.4.4 Pharmacology of G. indica

Vṛkṣāmla is a home remedy to treat several digestion problems like diarrhea and

dysentry, flatulence, allergies, burns, scalds, wounds. It is also a popular appetizer as

well as liver and cardio-tonic (Elumalai and Eswaraiah, 2011). However, it is most

popular as a obesity controlling herbal drug (Parthsarathy and Nandakishore, 2014)

Antioxidant activity: The water and alcoholic extracts of G. indica rinds (500mg/kg)

showed significant (P<0.01) antioxidant activity when studied using rodent models with

measure of sulphoxide dismutase (SOD), glutathione (GSH), lipid peroxidation (LPO) and

catalase (CAT). The activity was comparable to the standard drug silymarin (70 mg/Kg)

(Deore et al., 2011). Several preparations like Kokum syrup have antioxidant potential

due to the presence of garcinol and anthocyanins (Mishra et al., 2006). Yamaguchi et al.,

(2000) was also reported the free radical scavenging activity of garcinol against 2,2-

diphenyl-1-picrylhydrazyl (DPPH) radicals (Yamaguchi et al., 2000).

Anticancer activity: Garcinol has been studied for its anti cancer activity using several

models. Studies by Sang and co workers reported it to have better anti-tumor activity

when compared to curcumin. Garcinol induced apoptosis in human leukemia HL-60 Cells.

It was observed to have potent anti oxidant activity and inhibited Nitrous Oxide radical

generation and LPS-induced iNOS gene expression (Sang et al., 2002).


47

Hepatoprotective activity: G. indica aqueous and ethanolic extracts showed potent

hepato protection against carbon tetrachloride induced hepato-toxicity in Wistar albino

rats. There was a significant reduction in biochemical parameters i.e., aspartate

transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALKP) and serum

bilirubin (SBRN) (Deore et al., 2011).

Anti obesity activity: Several studies report the anti-lipidemic and anti obesity actions

of hydroxycitric acid (HCA). This compound was also reported to reduce blood sugar by

enhancing cellular consumption of glucose (Sullivan and Triscari, 1977). It inhibited

lipogenesis and increased activity of carnitine palmitoyl transferase (CPT 1), which is a

rate limiting factor in fat burning and thus helps in weight loss (Sullivan and Triscari,

1977). HCA was also observed to inhibit ATP:citrate lyase, an enzyme having an

influential role in fatty acid synthesis from carbohydrates. It catalyzes cleavage of citrate

to acetyl-CoA and oxaloactate (a molecule essential for the formation of fats from

carbohydrates) and regulates fatty acid synthesis. (Jena et al., 2002).

Antimicrobial and cytotoxic activity: Water extract of G. indica was active against

bacterial species Escherichia coli, Bacillus subtilis, Enterobacter aerogenes and

Staphylococcus aureus and fungi- Candida albicans and Penicillium. Its fruit rind extract

inhibited cultures of 3T3 mouse fibroblasts (Varalakshmi et al., 2010).

Anti ulcer activity: The aqueous and ethanol extract of Kokum showed protection

against gastric mucosal damage under experimental conditions. It was active in

preventing damage caused by multiple ulcer-inducers, viz., indomethacin, HCl and

ethanol. Oral administration of 500 mg/kg of Kokum extract were showed significant anti

ulcer activity in rat models (Deore et al., 2011).


48

2.6 Trans-disciplinary research (TDR) Methods

Several research problems, especially those originating from societal practices requires a

different approach than usual focused science research to solve them. They require a

trans-disciplinary research (TDR) model, which gives equal scope for ‘societal knowledge’

and ‘scientific knowledge’ (Lang et al., 2012) (Figure 2.9). TDR is the scientific inquiry

that cuts “across disciplines, integrates and synthesizes content, theory and methodology

from any discipline area and improves the quality, acceptance and sustainability of the

knowledge originating from research (Gray, 2008).

The research approaches to establish the legitimacy of different species used as Viḍanga

(Venkatasubramanian et al., 2013) and the studies performed to unravel the

bioequivalence of Ativiṣā and Mustā (Venkatasubramanian et al., 2010) are some of the

TDR approaches towards the concept of APD.

Figure 2.9: A simplified TDR model (Adapted from Lang et al., 2012)

SOCIETAL

PRACTICE

SCIENTIFIC

PRACTICE


49

2.7 Conclusion

The review of literature on APDs was undertaken to understand the contemporary

knowledge about the subject. Herbal medicine sector and Ayurveda practice is facing the

problems of unavailability of raw drugs, along with adulteration and unauthentic

substitution. In spite of stringent restrictions introduced by the Government, several

medicinal plant species are exploited.

In this scenario, the Ayurvedic concept of APD may be useful, but it is not properly

utilized. There is lack of clarity about the logic of selection of APDs in Ayurveda. There is

also noticeable dearth of systematic studies either from Ayurvedic and scientific

perspectives. Probably, all these factors inhibit the Ayurvedic drug sector to use and

regulatory authorities to permit the practice APDs.

The need for a systematic documentation of APDs both from Ayurvedic literature and

practices is observed from the literature survey. Further, the documented APDs have to

be analysed to understand the logic behind suggesting specific substitutes and the

worthiness of such APDs compared to the ADs. It requires a systematic, trans-disciplinary

research (TDR) approach to find the answers to several questions about APDs including

the logic, and to reach back to the stake holders.

chapter 2 review of literature -...

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