PHARMA SCIENCE MONITOR AN INTERNATIONAL … · An attempt has been made to review some flavonoids...
Transcript of 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
www.pharmasm.com IC Value – 4.01 2079
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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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.
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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.
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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.
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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,
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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]
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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.
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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
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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
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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
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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
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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]
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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.
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For Correspondence: Raghunath T. Mahajan Email: [email protected]