pharma science monitor an international … · an attempt has been made to review some flavonoids...

Vol-3, Issue-3, July-2012 ISSN: 0976-7908 Mahajan et al

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PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES

A NOVEL APPROACH TOWARDS PHYTOSOMAL FLAVONOIDS

Raghunath T. Mahajan* and Gunjan M. Chaudhari

Department of Biochemistry and Biotechnology, Moolji Jaitha College, Jalgaon-425002 ABSTRACT An attempt has been made to review some flavonoids rich medicinal plants of Maharashtra with the intention of their use in herbal drug delivery system. In this direction, a list of indigenous medicinal plants have been prepared with respect to the taxonomic name, vernacular names, family, parts used of these plants on the basis of literature. This article includes 181 medicinal plants of Maharashtra belonging to different 67 families. In the present review 27.07% trees, 17.13% shrubs, 48.07% herbs, few climbers, creepers and weeds are noted for the presence of flavonoids. Among the plant parts, mostly leaves contain more flavonoids than roots, stems, seeds, flowers, fruits and barks. The highest content of flavonoid as flavonol is present in Asteraceae family and an auntheticated chemotaxonomic marker of Asteraceae. Usually terpenes, edusmocoides, ginsenoside, flavonoids, epigallocatechi-3-o-gallate, procyanidins, flavones polyphenols are crucial candidates of phytosome. Relative lipophilicity and capacity constant K, hydroxylation pattern of C2-C3 is taken into consideration for final selection of most appropriate biomolecule as phytosome. These unique chemical characteristic and structure of flavonoids pose major challenge for the use of them in better absorption through tissues. The use of phytosomes is a novel formulation herbal technology which helps to reduce most of the problems arises in pharmacodynamics and bioavailability of drugs to achieve target effect. This paper provides details of the selection of flavonoids and formulation methodology for phytosomal flavonoids. Keywords: Phytosome, Flavonoids, Asteraceae, Bioavailability. INTRODUCTION

Plants have been associated with the human health from time immemorial and

they are importance source of medicines since the down of human civilization. Plants

have played a significant role in maintaining human health and improving quality of

human life since long and have served humans as well as valuable components of

medicine, beverages, cosmetics and dyes. The popularity of Herbal medicine in recent

time is based on the premise that plants contain natural substances that can promote

health and would help to alleviate illness. Therefore, the focus on plant research has

increased all over the world. Herbal drugs, medicinal plants, their extracts and isolated

compounds have showed a wide spectrum of biological activities. In spite of tremendous



developments in the field of allopathic medicines during the 20th century, plants still

remain one of the major sources of drugs in modern as well as in traditional systems of

medicine. India has rich heritage of natural wealth and biodiversity. Approximately, one

third of all pharmaceuticals are plant origin. [1] The medicinal plants are rich in source of

secondary metabolites like alkaloids, glycosides, steroids and flavonoids which are

potential source of drugs. Among these flavonoids and other phenolics have drawn

attention of researchers for their medicinal properties, especially their potential role in the

prevention of cancer and heart diseases. [2]

Flavonoids,the most common group of polyphenolic compounds that are found

ubiquitously in plants. These are widely distributed in plant fulfilling many functions.

Flavonoids and other plant phenolics are especially common in leaves, flowering tissues

and woody parts such as stems and bark. They are important in plant for normal growth

development and defence and defence against infection and injury. [2] Phytochemicals are

defined as the substances found in edible fruits and vegetables that exhibit a potential for

modulating human metabolism in a manner beneficial for the prevention of chronic and

degenerative diseases. [3] Flavonoids are the most important pigments for flower

coloration producing yellow or red/blue pigmentation in petals. Those colours are a mean

to attract pollinator’s animals. These secondary metabolites are known to have anti-

oxidant, anti-inflammatory, anti-microbial and anti-cancer activity, hepato and

nephrotoxicity protective activity.

The aim of this review is to compile indigenous medicinal plants of the Maharashtra

state containing flavonoids. Some light is also thrown on overview of chemistry of

flavonoids, its absorption followed by present knowledge on the phytosome as herbal

drug delivery system. In the last part of this review, the preparation of phytosome of

flavonoid is discussed.

Flavonoid in medicinal plants

Over 5000 naturally occurring flavonoids have been characterised from various

plants. [4] Many researchers have reported health promoting effects of flavonoids. An

important effect of flavonoids is the scavenging of oxygen derived free radicals. In vitro

experimental systems also showed that flavonoids possess anti-inflammatory,

antioxidant, anti-viral, and anti-carcinogenic properties. Research on flavonoids received



an added impulse with discovery that flavonoids in red wine are responsible to reduce

cardiovascular mortality rate. [5] Looking towards the increasing importance of flavonoids

an attempt has been made to review some flavonoids rich in some medicinal plants of the

state of Maharashtra with the intention of their use in herbal drug delivery system. In this

regard, a list of indigenous medicinal plants have been prepared with respect to the

taxonomic name, vernacular names, family, parts used of these plants on the basis of

literature. This article includes 181 medicinal plants of Maharashtra belonging to

different 67 families as shown in table- 1.

TABLE 1: A LIST OF MEDICINAL PLANTS CONTAINING FLAVONOIDS

Sr. No

Botanical Name Family Common name Plant type

Plant part used

1 Adhatoda vasica Nees. Acanthaceae

Adulsa S L

2 Ruellia tuberosa Linn. Acanthaceae

Ruwel H Wp

3 Andrographis paniculate Nees. Acanthaceae

Kalmegh/krit

H

L

4 Barleria prionitis Linn Acanthaceae

Kate-Korani

H

Fl, L

5 Agave sisalana Linn.

Agavaceae

Khetki S

Fr

6 Aerva lanata Linn.

Amaranthaceae

Madhuri, kapuri H

A

7 Achyranthes aspera Linn.

Amaranthaceae

Aghadha

H

Wp

8 Achyranthes bidentata Blume.

Amaranthaceae

Apmarg

H

R, St, L

9 Amaranthus spinosus Linn.

Amaranthaceae

Kathe math

H

L

10 Anacardium occidentale Linn.

Anacardiaceae

Kaju

T

Fr

11 Lannea coromandelica Merr.

Anacardiaceae

Shimti, shemat

T

B

12 Mangifera indica Linn.

Anacardiaceae

Mango

T

L, St, B, Fr, Sd

13 Buchanania lanzan Spreng

Anacardiaceae

Charoli

T

L

14 Annona squamosa Linn

Annonaceae

Custard apple

T

Sd, L



15 Anethum graveolens Linn.

Apiaceae

Shepu

H

L

16 Alstonia scholaris Linn.

Apocynaceae

Satpani

T

B

17 Catharanthus roseus Linn.

Apocynaceae

Sadafuli

H

L, R

18 Ichnocarpus frutescens Linn.

Apocynaceae

Kalidudhi

Cl

L

19 Acorus calamus Linn.

Araceae

Bacha

H

RH, L

20 Colocasia esculenta Linn.

Araceae

Alu/taro

H

L, Rh

21 Hemidesmus indicus R.Br

Ascalepiadaceae

Anantmul

Cr

R

22 Calotropis gigantea R.Br.

Ascalepiadaceae

Rajarka

S

R

23 Calotropis procera Linn.

Ascalepiadaceae

Rui, Akara

S

L

24 Aloe vera Linn.

Asphodelaceae

Korphad

H

L

25 Vernonia anthelmintica Linn. Asteraceae Kadu jire H Sd 26 Ageratum houstonianum Mill Asteraceae

Blue mink

H

L

27 Calendula officinalis Linn. Asteraceae

Zendu

H

L, Fl

28 Carathamus tinctorius Linn. Asteraceae

Kusum

S

Sd

29 Chrysanthenum indicum Linn.

Asteraceae

Shewanti

H

Fl

30 Echinopus echinatus Linn.

Asteraceae

Utakanta

H

R

31 Eclipta alba Hassk.

Asteraceae

Bhringraj

H

L, St, R

32 Elephantopus scaber Linn. Asteraceae

Hastipata

H

L, Rh

33 Guizotia abyssinica Linn. Asteraceae

Kala til

H

Sd

34 Parthenium hysterophorus Linn.

Asteraceae

Gajar gavat

H

L

35 Synedrella nodiflora Linn. Asteraceae

Node weed

W

L

36 Tridax procumbens Linn. Asteraceae

Dagadi pala, Ekdandi

H

R, St, Fl, L

37 Taraxacum officinale F.H.Wigg

Asteraceae

Kanphool

H

R



38 Vernonia arborea Hk.

Asteraceae

T

L

39 Vernonia cinerea Less.

Asteraceae

Sahdevi

H

Fl

40 Wedelia calendulacea Less.

Asteraceae

Bhringraj

H

L

41 Wedelia chinensis Merrill Asteraceae

Pila bhamgara H L

42 Wedlia wallichi Less Asteraceae

H Wp

43 Xanthium stumarium Linn. Asteraceae

Bondari

S

R

44 Sphaeranthus indicus Linn.

Asteraceae

Gorakhmundi

H

Wp

45 Barringtonia acutangula Linn. Barringtoniaceae

Sathafala

S

St

46 Basella alba Linn. Basellaceae

Indian spinach

Cr

L

47 Berberis aristata D.C. Berberidaceae

Daruhald

H

R, St

48 Betula pendula Roth.

Betulaceae

Bhojpatra

T

L

49 Jacaranda mimosifolia D. Don

Bignoniaceae

Blue jacaranda

T

L

50 Kigelia pinnata Jacq.

Bignoniaceae

Sonchampa

T

L

51 Millingtonia hortensis Linn.

Bignoniaceae

Kaval neem

T

L, Fl

52 Oroxylum indicum Linn. Bignoniaceae

Sonpatha

T

R, Sd

53 Bixa orellana Linn.

Bixaceae

Sundry

T

L

54 Cordia dichotoma Linn. Boraginaceae

Bhokara

T

Fr

55 Ehretia laevis Roxb.

Boraginaceae

Dhatrang

H

L, St

56 Comminphora mukul Hook. Burseraceae

Guggal

S

G

57 Cassia fistula Linn.

Caesalpinaceae

Bahava

T

L

58 Hardwickia binata Roxb. Caesalpinaceae

Anjan/ kamara

T

L, Sd

59 Cassia auriculate Linn. Caesalpinaceae

Tarvad

S

L

60 Cassia Tora Linn. Caesalpinaceae Takla S Fr



61 Saraca asoka Roxb.

Caesalpinaceae

Ashok

T

B, Fl

62 Senna surattensis Burm. F Caesalpinaceae

Motha farvad

S

L

63 Tamarindus indica Linn

Caesalpinaceae

Imli

T

R, Fl

64 Cannabis sativa Linn.

Cannabaceae

Ganja

H

L

65 Carica papaya Linn

Caricaceae

Papaya

T

Sd

66 Celastrus panniculatus Willd

Celastraceae

Jotismti

Cr

Sd

67 Anogeissus acuminata Roxb. Combretaceae

Sonchampa

S

St

68 Anogeissus Latifolia Roxb

Combretaceae

Dhava

S

St, L

69 Combretum roxburghii Spreng.

Combretaceae

Kala Atundi

T

R

70 Quisqualis indica Linn.

Combretaceae

Lal chameli

S

L, St

71 Arctium lappa Linn.

Compositae

Great Burdock

H

R

72 Argyreia speciosa Linn.

Convolvulaceae

Vrudhadaruka

H

R

73 Cuscuta reflexa Roxb.

Convolvulaceae

Akashbela

H

St

74 Xanthium stumarium Linn.

Curcurbitaceae

Bondari

H

Fr

75 Momordica charantia Linn.

Curcurbitaceae Karle

H

Sd

76 Tricosanthes dioica Roxb.

Curcurbitaceae Palta

Cl

L, St

77 Cyperus rotundus Linn

Cyperaceae

Nagarmotha

H

Rh

78 Baliospermum monatanum Muell.

Euphorbiaceae

Danti

S

L

79 Breynia vitis-idaea (Burm.f.)

Euphorbiaceae

Pandharfal

S

L

80 Phyllanthus emblica Linn.

Euphorbiaceae

Awala

T

B, Fr

81 Phyllanthus Urinaria Linn.

Euphorbiaceae

Valaiti saunf, muhuri

H

St

82 Acalypha indica Linn.

Euphorbiaceae

Khokli/kappi

H

Wp



83 Arachis hypogaea Linn.

Fabaceae

Shengdana

H

St

84 Butea monosperma (Lam)

Fabaceae

Palas

S

St, B

85 Cajanus scarabaeiodes Linn.

Fabaceae

Rantur, banna adhaki

H

Wp

86 Clitoria ternatea Linn

Fabaceae

Aparijita

H

R, Sd

87 Derris heyneana Benth

Fabaceae

Garwel

S

R

88 Glycyrrhiza glabra Linn.

Fabaceae

Mulethi

S

R

89 Bauhinia monandra Kurtz.

Fabaceae

Butterfly

T

L, Fl

90 Pongamia pinnata Linn

Fabaceae

Karanj

T

Fl

91 Tephrosia purpurea Linn

Fabaceae

Unhali/utali

H

Sd, L

92 Exacum bicolor Roxb.

Gentianaceae

Akshipushpi

H

Fl, Wp

93 Biophytum sensitivum Linn.

Gerandaceae

Lajalu

H

L

94 Cynodon dactylon Linn.

Graminae

Durwa

H

R, Wp

95 Hordeum vulgare Linn.

Graminae

yava/ barley

H

Sd

96 Crocus sativum Linn.

Iridaceae

Kumkuma

S

Fl

97 Ocimum basilicum Linn

Labiatae

Sabja

H

L

98 Hyptis suaveolens Linn.

Lamiaceae

Gangatulas

H

L

99 Leucas ciliate Benth

Lamiaceae

Burumbi

H

L

100 Leucas plukeneti Roth.

Lamiaceae

Chhota halkussa H

Wp

101 Salvia plebeian R. Brown

Lamiaceae

Babul

H

L

102 Mentha longifolia Linn Lamiaceae

Gawthi pudina

H

L

103 Orthosiphon stamineus Benth

Lamiaceae

Mutri tulsi H

L

104 Cassytha filiformis Linn.

Lauraceae

Akashwel/amarwel

H

Fr

105 Bauhinia purpura Linn. Leguminoceae Lai-kovidar T L, Sd



106 Bauhinia racemosa Linn.

Leguminoceae

Apata

T

L, Sd

107 Caesalpinia sappan Linn.

Leguminoceae

Kuchandan

S

Sd

108 Cassia hirsuta Linn.

Leguminoceae

Bahava H

L

109 Cedrela toona Roxb.

Leguminoceae

Tuni

H

Sd

110 Tephrosia purpurea Linn

Leguminoceae

Sarwa/Wranvishapaka

H

L

111 Albizzia lebbeck Benth.

Leguminoceae

Shirisa

T

L, St

112 Sesbania sesban (L.) Merr.

Leguminoceae

Shewarie

T

L, Fl

113 Allium cepa Linn.

Liliaceae

Kanda

H

Tu

114 Asparagus gonocladus Linn.

Liliaceae

Satmuli

S

R

115 Asparagus racemosa Willd

Liliaceae

Shatawari

Cr

R

116 Loranthus longiflorus Linn. Loranthaceae

Bandgud/ kangudi

Cl

L

117 Magnolia champaca Linn.

Magnoliaceae

Champa

T

Fl, Fr

118 Soymida febrifuga Roxb.

Maliaceae

Rohini/potar

T

B

119 Azadirachta indica A Juss.

Maliaceae

Kadunimb

T

L

120 Abutilon indicum Linn

Malvaceae

Atibal, mudra/petari

S

Wp

121 Hibiscus cannabinus Linn

Malvaceae

Ambadi

H

L

122 Tinospora cordifolia Miers

Menispermaceae

Gulvel

Cr

L

123 Acacia arabica Lam.

Mimosaceae

Babul

T

L

124 Acacia catechu Linn.

Mimosaceae

Khair

T

B

125 Acacia sinuate Linn.

Mimosaceae

Cikaki

S

B

126 Mimosa pudica Linn.

Mimosaceae

Lajalu

S

L

127 Ficus bengalensis Linn.

Moraceae

Vad

T

St



128 Ficus religiosa Linn.

Moraceae

Pipal

T

L, St

129 Moringa oleifera Lamk.

Moringaceae

Sajina

T

R

130 Musa sapientum Linn.

Musaceae.

H

Fl

131 Embelia robusta Roxb.

Myrsinaceae

Baybran

Cl

Fr

132 Embelia basal Roxb.

Myrsinaceae

Vidanga

Cl

Fr

133 Embelia ribes Roxb.

Myrsinaceae

Jantughn/ vayuvidang

Cl

Fr

134 Boerhaavia diffusa Linn.

Nyctaginaceae

Punarnava

H

R, Wp

135 Argemone mexicana Linn.

Papaverceae

Katuparni

H

R, L

136 Chelidonium jajus Linn.

Papaverceae

Celandine

H

Fl

137 Indigofera aspalathoides Vahl.

Papilionaceae

Lavang

S

St

138 Passiflora incarnate Linn.

Passifloraceae

Gandhali

H

L, R

139 Adiantum Lunulatum Burm.

Polypodiaceae

Hansraj

H

L

140 Nigella sativa Linn.

Ranunculacae

Kalunji/ kaljaji

H

Sd

141 Anthocephalus cadamba Roxb.

Rubiaceae

Kadamba

T

R, St

142 Borreria hispida Linn.

Rubiaceae

Madanghati

H

R

143 Gardenia gummifera Linn.

Rubiaceae

Dikamali

S

St

144 Aegle marmelos Linn.

Rutaceae

Bel

T

Fr

145 Chloroxylon swietenia DC.

Rutaceae

Bherua

T

B, L

146 Citrus decumana Linn.

Rutaceae

Baranimbu

S

L, Sd

147 Murraya koenigii Linn.

Rutaceae

Curry L

H

L

148 Toddalia asiatica Linn.

Rutaceae

Jangli kali mirch

T

L

149 Citrus medica Linn.

Rutaceae

Bijora nimbu

S

Fr

150 Schleichera oleosa (Lour.) Sapindaceae Kosimb/ Kusum T B



151 Digitalis purpurea Linn.

Scrophulariaceae

Hrupatri

H

L

152 Bacopa moneirra Linn.

Scrophulariaceae

Nirabramhi/ bramhi

H

L

153 Limnophila indica Linn.

Scrophulariaceae

Ambuli/ amragandh

W

R, A

154 Ailanthus excels Roxb.

Simaroubaceae

Mahanimb/ madala

T

R

155 Balanites roxburghii Planch.

Simaroubaceae

Hingana

T

St

156 Dhatura fastuosa Linn.

Solanaceae

Dhutura

H

L, Sd

157 Solanum nigrum Linn

Solanaceae

Kangni/ringni/ nightshade

H/ S

L

158 Coscinium fenestratum Gartn. Stercularaceae

Jhade-halde/ daruharidra

H

Wp

159 Tilia chordate Mill.

Tiliaceae

Lime flower/ lindane

T

Fl

160 Apium graveolens Linn.

Umbelliferae

Ajmoda

H

R

161 Centilla asiatica Linn.

Umbelliferae

Mandukparni

H

Sd, Wp

162 Coriandrum salivum Linn.

Umbelliferae

Dhaniya

H

L, Fl

163 Cuminum cyminum Linn.

Umbelliferae

Jire/gire/zira

H

Sd

164 Daucus carota Linn.

Umbelliferae

Carrot

H

R, L

165 Pimpinella anisum Linn.

Umbelliferae

Tuberose, Rajanigandha

H

St

166 Urtica dioica Linn.

Urticaceae

Guelder Rose

H

R

167 Gmelina arborea Roxb.

Verbenaceae

Shivan

T

L

168 Premna serratifolia Linn.

Verbenaceae

Agnimantha

S

L

169 Vitex leucoxylon Linn.

Verbenaceae

Sheras/ songarbi T

Fl

170 Vitex negundo Linn.

Verbenaceae

Nirgundi/ nirgud

T

R

171 Vitex pinnata Linn.

Verbenaceae

Majurgudia

T

L

172 Clerodendrum phlomidis Linn.

Verbenaceae

Agnimantha

T

R, L



173 Clerodendrum serratum Linn.

Verbenaceae

Bharangi T R, L

174 Cayratia camosa Lam.

Vitaceae

Ambatvel

Cl

R

175 Cissus quadrangularis Linn.

Vitaceae

Asthisamhari

S

L, St, R

176 Curcuma aromatica Salisb.

Zingiberaceae

Jangali halad

H

R

177 Curcuma longa Linn.

Zingiberaceae

Haridra

H

Rh

178 Curcuma zedoria Rosc.

Zingiberaceae

Ekangi

H

Rh

179 Zingiber officinale Linn.

Zingiberaceae

Ginger

H

Rh

180 Balanites aegyptiaca Linn. Zygophyllaceae

Hingan

T

L, St, R

181 Tribulus terrestris Linn. Zygophyllaceae

Chota gokeru

H

Wp

H- herb, S- shrub, T-tree, Cl- climber, Cr- creeper, W-weed, R-root, L-leaf, St-stem, Sd-seed, Wp-Whole

plant, Fl- flower, Fr- Fruit, Rh- rhizome, B-bark, A-aerial part, Tu-tuber and G-gum.

TABLE 2: FREQUENCY OF MEDICINAL PLANTS IN FAMILY AS PER

DISTRIBUTION OF FLAVONOIDS

Family Number of plants 32 families with only 1 plants 1 13 families with only 2 plants 2 Apocynaceae 3 Ascalepiadaceae Curcurbitaceae Liliaceae Myrsinaceae Rubiaceae Scrophulariaceae Acanthaceae 4 Amaranthacea Anacardiaceae Bignoniaceae Combretaceae Mimosaceae Zingiberaceae Euphorbiaceae 5 Lamiaceae 6 Umbelliferae



Caesalpinaceae 7 Verbenaceae Leguminoceae 8 Fabaceae 9 Rutaceae Asteraceae 20

Araceae, Boraginaceae, convolvulaceae, Gerandaceae, Graminae, Maliaceae,

Malvaceae, Moraceae, Papaverceae, Simaroubaceae, Solanaceae, Vitaceae and

Zygophyllaceae these family have two plants as seen in above table.

Agavaceae, annonaceae, Apiaceae, Asphodelaceae, Barringtoniaceae,

Basellaceae, berberidaceae, Betulaceae, Bixaceae, Burseraceae, Cannabaceae,

Caricaceae, Celastraceae, Compositae, Cyperaceae, Iridaceae, Labiatae, Lauraceae,

Loranthaceae, Magnoliaceae, menispermaceae, Moringaceae, Musaceae, Nyctaginaceae,

Papilionaceae, Passifloraceae, Polypodiaceae, Ranunculacae, Sapindaceae,

stercularaceae, Tiliaceae, and Urticaceae these family have single plant as seen in above

table.

Figure 1 Family wise distribution of medicinal plants containing flavonoids



From the figure1, it is observed that Asteraceae is a richest in flavonoids.

TABLE 3: HABIT WISE DISTRIBUTION OF FLAVONOIDS

Plant habit Number of plants % of Habit Weed 2 1.10

Creeper 5 2.76 Climber 7 3.87 Shrub 31 17.13 Tree 50 27.62 Herb 86 47.51

Figure 2 Plant habit wise distributions of flavonoids

It is evident from the above figure 2 that flavonoids are mostly present in herbs

followed by trees, shrubs, and very few in climbers, creepers and weeds.



TABLE 4: PLANT PART WISE DISTRIBUTION OF FLAVONOIDS

Plant part used

Number of

plants Gum 1 Tuber 1 Aerial part 2 Rhizome 7 Bark 11 Fruit 13 Whole plant 14 Flower 19 Seed 22 Stem 25 Root 39 Leaf 84

Figure 3 Flavonoids distribution in various plant parts

From the figure 3, it is observed that frequency of flavonoid is generally higher in

the leaves of medicinal plant which is followed by root, stem, seed, whole plant, flower,

fruit, rhizome, bark and very few in gum and pod.



Chemistry of flavonoids

One of the largest classes of naturally occurring polyphenolic compounds are the

flavonoids. [6] This group of plant pigments is largely responsible for the colors of many

fruits and flowers and over 4,000 flavonoid compounds have been characterized and

classified according to chemical structure. [7] The word flavonoid comes from the Latin

flavus which means yellow; however some flavonoids are red, blue, or purple or white. [8]

Chemically they are C6-C3-C6 compounds in which the two C6 groups are

substituted benzene ring, and the C3 is an aliphatic chain which contains a pyran ring. [9]

Flavonoids occure as O-or C-glycolsides or in a free state as aglycones with hydroxyl or

methoxyl groups present on the aglycones. [8]

Flavonoids can be divided into various classes on the basis of their molecular

structure. [10] The flavonoids may be divided into seven types: flavones, flavonols,

flavonones, chalcones, xanthones, isoflavones and biflavones. [11] The molecular structure

of four main groups of flavonoids together with the best known members of each group is

as follows:

Flavones are characterized by planar structure because of a double bond in the

central aromatic ring. One of the best described flavonoids, quercetin is member of this

group.

Flavone Quercetin

The second group is the flavonones, narigin is the example of this group of flavonoids.



Flavanones Naringenin

The third group is the catechins, epicatechins is the example of this group of flavonoids

Catechins Epicatechins

The fourth group is the anthocyanins, cyanidin is the example of this group of flavonoids

Anthocyanins Cyanidin

Flavonoids have been shown to be good taxonomic markers for Asteraceae.

Flavonoids have a wide structural diversity and have been isolated in great scale from

Asteraceae species, they can be used as taxonomic markers at lower hierachial levels. [12]

Usually terpenes, edusmocoides, ginsenoside, flavonoids, epigallocatechi-3-o-gallate,



procyanidins, flavones polyphenols are crucial candidates of phytosome. Relative

lipophilicity and capacity constant K, hydroxylation pattern of C2-C3 is taken into

consideration for final selection of most appropriate biomolecule as phytosome. These

unique chemical characteristic and structure of flavonoids pose major challenge for the

use of them in better absorption through tissues. The use of phytosomes is a novel

formulation herbal technology which helps to reduce most of the problems arises in

pharmacodynamics and bioavailability of drugs.

Background of the study

Over the past century, chemicals and pharmacologic science established the

compositions, biological activities and health giving benefits of numerous plant extracts.

But ofetn when individual component were seperated from the whole there was loss of

activity- the natural ingredientsynergy became lost. [13] Standardizatioon was developed

to solve this problem. As standardized extracts became established, poor bioavailability

often limit their clinical utility.this is because most of bioactive constituents of

phytomedicine were water soluble molecules (eg. Phenolics, glycosides, flavonoids).

However water phytoconstituents are limited in their effectiveness because they are

poorly absorbed [14] when taken orally or when applied topically. Many approaches have

been developed to improve the oral bioavailability, such as inclusion of solubility and

bioavailability enhancers, structural modification and entrapment with lipophilic carriers.

[15, 16, 17] There are many factors which may contribute to the poor bioavailability. For

example, many phytoconstituents have multiple rings and, therefore, cannot be absorbed

from the intestine into the blood by simple diffusion. Also, some herbal phytomolecules

are poorly miscible with oils and other lipids and often fail to pass through the small

intestine because of its lipoidal nature. The effectiveness of any herbal product is

dependent upon delivering an effective level of the active compounds. Then it is reported

that complexion with certain other clinically useful nutrients substancially improved the

bioavailability of such extracts. The nutrients so helpful for absorption of other nutrients

are the phospholipids. This has helped a lot in increasing the bioavailability of

phytoconstituents. And in this attempt different drug delivery systems were discovered

called as "somes" as follows [18]



The "Somes" the cells like formulations of novel drug delivery system. There are

different types of somes like

Ø Liposomes, which encapsulate water and lipid-soluble pharmacologically and

cosmetically active components.

Ø Phytosomes are standardized extracts or purified fractions complexed with

phospholipids for a better bioavailability and enhanced activities.

Ø Cubosomes are bicontinuous cubis phases, consisting of two separate,

continuous, but nonintersecting hydrophilic regions divided by lipid layer thatis

controlled into a periodicminimal surface with zeroaverage curvature.

Ø Colloidosomes are solid microcapsules formed by self assembly of colloidal

particles at the interface of emulsion droplets. 'Colloidosomes" are hollow,

elastic shells whose permeability and elasticity can be precisely controlled.

Ø Ethosomes are noninvasive delivery carriers that enable the drug to rich deep

skin layers and / or the systemic circulation. Ethosomes contain phospholipids,

alcohol(ethanol and isopropyl alcohol) in relatively high concentration and

water.

Ø Aquasomes- these are spherical 60-300nm particles used for drugs and antigen

delivery. The particle core is composed of noncrystalline calcium phosphate or

ceramic diamond, and is covered by polyhydroxyl oligomeric film.

Ø Pharmacosomes are the colloidal dispersions of drugs covalently bound to lipid

and may exist as ultrafine vesicular, miscillar, or hexagonal aggregates,

depending on the chemical structure of the drug-lipid complex.

Phytosome – A herbal drug delivery system

As discussed above most of the bioactive constituents of phytomedicines are

flavonoids (e.g. Anthocyanidins from bilberry, cathechins from green tea, silymarin from

milk thisle). However, many flavonoids are poorly absorbed. [14] This poor absorption of

flavonoid is mainly due to two reasons. First, they are multiple ring molecules too large

that it can not be absorbed by simple diffusion. Second they have poor miscibility with

oils and other lipids, they are limited in their ability to pass across the lipid rich outer

membrane of enterocytes of the small intestine. The phytosome technology would meet

this challenge.



Water soluble flavonoid molecule can be converted into lipid compatible

molecular complexes, namely phytosomes. Phytosomes are better able to transitio from

hydrophilic environment into the lipid friendly environment of the enterocyte cell

membrane and from there into the cell, finally reaching the blood. [19] Lipid substances

employed to make flavonoid lipid compatible are phospholipid from soy, mainly

phosphatidylcholine (PC). It is miscible in both water and in oil/lipid environment and is

well absorbed when taken by mouth. Precise chemical analysis indicates a phyotsome is

usually a flavonoid molecule linked with al least one phosphatidylcholine molecule. A

Bond is formed between the two molecules, creating a hybrid molecule. This highly lipid

miscible hybrid bond is better suited to merge into lipid phase of the outer cell membrane

of the enterocytes.

Phosphatidylcholine is not merely a passive "carrier" for the flavonoids of the

phytosomes, but is itself bioactive nutrient with documented clinical efficacy for liver

disease, including alcoholis hepatic steatsis, during induced liver damage, and hepatitis.

[20] Phytosomes are not liposomes and, structurally the two are very different as shown in

Figure 4.

Unlike phytosomes, liposomes are formed by mixing a water-soluble substance

with phosphatidylcholine. No chemical bond is formed and the phosphatidylcholine

molecules surround the water soluble substance. There may be hundreds or even

thousands of phosphatidylcholine molecules surrounding the water-soluble compound.

[21]

Phosphatidylcholine-drug

complex

Phosphatidylcholine

Water soluble free drug

Liposome

Phytosome

Figure 4 Showing structural differences between Phytosome and Liposome



Some of the herbal phytosomal preparations which are prepared from flavonoids

are as follows

TABLE 5: A LIST OF SOME KNOWN REPUTED PHYTOSOME DEVELOPED

Formulation Active ingredients

Ginkgo biloba phytosome Flavonoids

Silybin phytosome Silybin

Green tea phytosome Epigallocatechin

Ginseng phytosome Ginsenosides

Hawrthorn phytosome Flavonoids

Quercetin phytosome Quercetin

Cucurmin phytosome Cucurmin

Naringenin phytosome Naringenin

Marsupin phytosome Marsupin

Source:Patel et al.,2009,4(6):363-371

Silybin Quercetin

Cucurmin Naringenin



Marsupium

Phosphatidylcholines (PC) are a class of phospholipids that incorporate choline

as a headgroup. They are a major component of biological membranes and can be easily

obtained from a variety of readily available sources such as egg yolk or soy beans from

which they are mechanically extracted or chemically extracted using hexane. They are

also a member of the lecithin group of yellow-brownish fatty substances occurring in

animal and plant tissues.

Phosphatidylcholine

Preparation of phytosome

Phytosomes are formulated by patented processes in which the standardized

extracts (having a standardized content of active principle) and / or active ingredients of

herbs (like flavolignans and terpenoids) are bound to the phospholipids like

phosphatidylcholine (PC) through a polar end. The phytosome process produces small

cells which protect the valuable component of the herbal extract from destruction by

digestive secretions and gut bacteria. [22] They improve transition of constituents from



water phase to the enterocytes of the gut wall and ultimately they reach the circulation.

The phytoactive components of these herbal extracts are well suited to directly binding to

phosphatidylcholine from the soy. PC is also the principle molecular building block of

cell membranes and is miscible with both water and oil/ lipid mixtures, and is well

absorbed orally. Phospholipids are small lipid molecules in which the glycerol is bound

to only two fatty acids, instead of three as in triglycerides, with the remaining site is

occupied by a phosphate group. [23] Specifically, the choline head of the

phosphatidylcholine molecule binds to phytoconstituents while the fat-soluble

phosphatidyl portion, comprising the body and tail, then envelops the choline bound

material. This results in small microshperes or the production of cells known as

phytosomes. [22, 23, 24]

Thus phytosomes are also considered as phytolipid delivery system. [25]

Phytosomes are prepared by reacting 3-2 moles (preferably with one mole) of natural or

synthetic phospholipid, such as phosphatidylcholine, phosphatidylethanolamine, with one

mole of phytoconstituents either alone or in natural mixture in an aprotic solvent, such as

dioxane or acetone in a 1:2 or 1:1 ratio. [26] The optimum ratio of phospholipid to

phytoconstituent is 1:1. The complex thus formed can be isolated by percipitation with an

aliphatic hydrocarbon or lyophilization or spray drying. [27] Some liposomal drug

complexes operate in the presence of water or buffer solution where the phytosomes

interact with a solvent with reduced dielectric constant. The common stages for the

preperation of phytosomes [28] are given in Figure 5.

Phospholipids

Dissolved in organic solvent containing Drug/Extract

Hydration

Solution of phospholipids in organic solvent with drug/extract

Drying



Formation of thin film

Formation of phytosomal suspension

Figure 5 General stages for preparation of phytosomes

Earlier researchers described methods used for phytosome preparation. [29, 30, 31].

Jiang et al., have optimized the preperation conditions using a uniform design and step

regression and have prepared Herba Epmedii total flavonoid phytosome (EFP) by means

of solvent evapouration and investigated the cumulation dissolution of different ratios of

EFP-PVP precipitate by means of dissolution release. The optimized preperation

conditions are as follows: solvent-tertahydrofuran, lecithin to PVP ratio 2.5, temperature

40˚C and reaction time 3 hrs. The oil/water apparent partition coefficient of icariin was

enhanced more than 4 fold by phospholipid. The cumulative dissolution of Herba

Epimedii flavonoids of the EFP-PVP precipitate was significantly higher than that of its

physical mixture and a Herba Epimedii extract tablets. [29]

Mechanism of phytophospholipid complex (phytosome) formation

Phytosome results from the reaction of a stoichiometric amount of the

phospholipid (phosphatidylcholine) with the standardized extract or polyphenolic

constituents (like simple flavonoids) in a non polar solvent. Phosphatidylcholine is a

bifunctional compound, the phosphatidyl moiety being lipophilic and the choline moiety

being hydrophilic in nature. Specifically the choline head of the phosphatidylcholine

molecule binds to these compounds while the lipid soluble phosphatidyl portion comprisg

the body and tail which then envelopes the choline bound material. Hence, the

phytoconstituents produce a lipid compatible molecular complex with phospholipids, also

called as phytophospholipid complex. Molecules are anchored through chemical bonds to

the polar choline head of the phospholipid. Precise chemical analysis indicates the unit

phytosome is usually a flavonoid molecule linked with at least one phosphatidylcholine

molecule. The result is a little microsphere or cell is produced. [32]



Advantage of phytosome

Phytosome have the following advantages. [33]

Ø It enhance the absorption of herbal constituent and hence the bioavailability.

Ø By enhancing the solubility of bile to herbal constituent, facilitates the liver

targeting.

Ø As the absorption of chief phytoconstituent is improved, its dose requirement is

also reduced.

Ø Phosphatidylcholine used in the preparation of phytosome, besides acting as

carriers also act as hepatoprotective, hence giving the synergestic effect.

Ø Unlike liposome, Chemical bonds are formed between phosphatidylcholine

molecule and phytoconstituents, so the phytosome show better stability profile.

Ø Phytosome are widely used in cosmetics due to their more skin penetration and

high lipid profile.

CONCLUSION

Flavonoids are bioactive phytomolecules difficult to absorb in target tissue in it's

native form. Therefore it is necessary to bring them in alternative form or state in order to

enhance their bioavailability and absorption capacity. Earlier researchers used to prepare

such a dynamic molecules using liposomes, however liposomes are formed by mixing a

water-soluble substance with phosphatidylcholine. No chemical bond is formed and the

phosphatidylcholine molecules surround the water soluble substance. And in phytosome

phospholipid-substrate interaction is due to the formation of hydrogen bonds between the

polar head of phospholipids and the polar functional groups of the substrate. This review

includes opportunities to select most common useful plants, abundantly available in

Maharashtra region. Hence appropriate plant will be selected to proceed for its plant

extract flavonoid isolation and phytosome utilization for the treatment severe disease

condition. The present approach will include the use of modern technology for drug as

well as drug delivery system.

ACKNOWLEDGEMENTS

Authors are thankful to the Principal and authorities of Moolji Jaitha College,

Jalgaon, Maharashtra, India for facilities and encouragement.



REFERENCES

1. Upadhyaya S, Khatiwora E, Saikia L: Comparison of total phenol and

flavonoid content in Adhatoda vasica Nees : Grown using different organic

manure. Journal of Pharmacy Research 2010; 3(10): 2408-2409.

2. Kahkonen MP, Hopia AI, Vuorela JH, Rauha JP, Pihlaja K, Kujala TS, Heinonen

M: Antioxidant activity of plant extracts containing phenolic compounds. J.

Agric Food Chem 1999; 47: 3954-3962.

3. Tripoli E, Guardia ML, Giammanco S, Majo DD, Giammanco M: Citrus

flavonoids: Molecular structure, biological activity and nutritional properties: A

review. Food Chemistry 2007; 104: 466-479.

4. Harborne JB, Williams CA: Advances in flavonoid research since 1992.

Phytochemistry 2000; 55: 481-485.

5. Nijveldt RJ et al, Flavonoids: a review of probable mechanisms of action and

potential applications. Am J Clin Nutr 2001; 74: 418–25.

6. Geissman TA, Crout DH: Organic Chemistry of Secondary Plant Metabolism.

San Francisco: Freeman, Cooper & Company 1969; 183-230.

7. Murray MT:. Encyclopedia of Nutritional Supplements. California: Prima

Publishing. 1996; 320-331.

8. Mills S, Bone K: Principles and Practice of Phytotherapy –Modern Herbal

Medicine. New York: Churchill Livingstone. 2000; 31-34.

9. Robinson T: The Organic Constituents of Higher Plants – Their Chemistry and

Interrelationships. North Amherst: Cordus Press, sixth edition 1991; 187-217.

10. Rice-Evans CA, Miller NJ, Paganga G: Structure-antioxidant activity

relationships of flavonoids and phenolic acids. Free Radic Biol Med 1996; 20:

933–56.

11. Evans WC: Trease and Evans Pharmacognosy. New York: W B Saunders,

Fifteenth edition 2002; 246-248.

12. Emerenciano VP, Militao JSLT, Campos CC, Romoff P, Kaplan MAC, Zambon

M, Brant AJC: Flavonoids as chemotaxonomic markers for Asteraceae.

Biochemical Systematics and Ecology 2001; 29: 947–957.



13. Bhattacharya S, Ghosh A: Phytosomes: The Emerging Technology for

Enhancement of Bioavailability of Botanicals and Nutraceuticals. The Internet

Journal of Aesthetic and Antiaging Medicine 2009; 2 : Number 1.

14. Manach C, Scalbert A, Morand C: Polyphenols: food sources and bioavailability.

Am. J. Clin. Nutr 2004; 79: 727-747.

15. Venkatesan N, Babu BS, Vyas SP: Protected particulate drug carriers for

prolonged systemic circulation–a review. Indian J. Pharm. Sci. 2000; 62: 327-

333.

16. Longer MA, Ching HS, Robinson JR: Oral delivery of chlorothiazide using a

bioadhesive polymer. J. Pharm. Sci 1985; 74: 406-411.

17. Sharma S, Sikarwar M: Phytosome: a review. Planta Indica 2005; 1: 1-3.

18. Vinod KR, Sandhya S: A review on genesis and characterization of phytosomes.

International Journal of Pharmaceutical Sciences Review and Research 2010; 4:

Issue 3, Article 013.

19. Bombardelli E, Curri SB, Della LR, Del NP, Tubaro A, Gariboldi P: Complexes

between phospholipids and vegetal derivatives of biological interest. Fitoterapia

1989; 90: 1-9.

20. Kidd PM: Phosphatidylcholine (Monograph). Alternative Medicine Review

Monographs. Thorne Research, Inc 2002; 1: 310-315.

21. Patel J, Patel R, Khambholja K, Patel N: An overview of phytosomes as an

advanced herbal drug delivery system. Asian Journal of Pharmaceutical Sciences

2009; 4 (6): 363-371.

22. Dubey D, Shrivastava S, Kapoor S et al: Phytosome: a novel dosage structure,

http://www.pharmainfo.net/reviews/ phytosome-novel-dosage-structure 2007.

23. Citernesi U, Sciacchitano M : Phospholipids/active ingredient complexes. Cosm.

& Toil 1995 ; 110: 57-68.

24. Murray MT: Phytosomes: Herbal Support – Increase the Absorption of Herbal

Extracts, Available at www. doctomurray.com/articles/silybin.htm. 2004.

25. Gupta A, Ashawal MS, Saraf S: Phytosomes: a novel approach towards functional

cosmetics. J. Plant Science 2007; 644-649.



26. Marena C, Lampertico M: Preliminary clinical development of silipide: A new

complex of silybin in toxic liver disorders. Planta Med 1991; 57: A124-A125.

27. Mascarella S: Therapeutic and antilipoperoxidant effects of silybin-

phosphatidylcholine complex in chronic liver disease. Curr. Ther. Res 1993; 53:

98-102.

28. Jain N K: Liposomes as drug carriers, controlled and novel drug delivery. CBS

publisher. First edition. 2005:308.

29. Jiang YN, Yu ZP, Yan ZM et al: Preparation of herba epimedii flavanoid and

their pharmaceutics. Zhongguo Zhong Yao 2001; 26: 105-108.

30. Maiti K, Mukherjee K, Gantait A, et al: Curcumin phospholipid complex:

preparation, therapeutic evaluation and pharmacokinetic study in rats. Int. J.

pharm 2006.

31. Maiti K, Mukherjee K, Gantait A, et al: Enhanced therapeutic potential of

naringenin-phospholipid complex in rats. J. Pharm. Pharmacol 2006; 58: 1227-

1233.

32. Franco PG, Bombardelli E: Complex coppouns of bioflavonoids with

phospholipids, their preparation and uses and pharmaceutical and cosmetic

compositions containing them. 1998; U.S. Patent No-EPO 275005.

33. Thurapati PR, Mettu SR, Veerareddy P R: Phytosome: A novel phyto-

phospholipid carriers for herbal drug delivery. IRJP 2011; 2(6): 28-33.

For Correspondence: Raghunath T. Mahajan Email: [email protected]

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