(TANNINS)
5 Plants containing the secondary
metabolite (Tannins). there medicinal uses,
traditional uses, there chemical structures
and qualitative tests for this secondary
metabolite.
BY
Anumah Abdulraheem okehi
COURSE: CH514 (Natural product chemistry)
COURSE LECTURER: Prof. H.M. Adamu
ContentsAbstract.................................................................................................................................................4
Acknowledgement.................................................................................................................................4
1
Introduction...........................................................................................................................................5
So what are tannins?..........................................................................................................................6
Classification of the tannins based on their structural properties...........................................................8
Different polyol units of the tannins......................................................................................................9
Different galloyl derivatives of gallotannins, ellagitannins, and complex tannins...............................10
Single tannin classes............................................................................................................................12
Gallotannins.....................................................................................................................................12
Ellagitannins....................................................................................................................................15
Complex tannins..............................................................................................................................19
Condensed tannins...........................................................................................................................19
Plants containing Tannins....................................................................................................................22
1. Aloe Vera (Aloe barbadensis Miller}................................................................................................22
Medicinal Uses................................................................................................................................23
Aloe Helps with Digestion...........................................................................................................23
1. Aloe Helps in Detoxification...................................................................................................23
2. Aloe Alkalizes the Body.........................................................................................................23
3. Cardiovascular Health.............................................................................................................23
4. Aloe Helps Boost the Immune System...................................................................................23
5. Aloe Vera is Great for the Skin...............................................................................................24
Traditional uses...............................................................................................................................24
2. Tea Tree (Melaleuca alternifolia}.....................................................................................................25
Medicinal Uses................................................................................................................................26
Traditional uses...............................................................................................................................27
3. Lemon balm (Melissa Officinalis).....................................................................................................29
Medicinal uses.................................................................................................................................30
Traditional uses...............................................................................................................................32
4. Thyme (Thymus Vulgaris)................................................................................................................33
Tra ditional uses of thyme...............................................................................................................34
Medicinal uses.................................................................................................................................35
5. Chamomile (Matricaria chamomilla L.)............................................................................................38
Traditional uses...............................................................................................................................40
Medicinal uses.................................................................................................................................41
Anti-inflammatory and antiphlogistic properties.........................................................................41
Anticancer activity.......................................................................................................................41
2
Common cold..............................................................................................................................41
Cardiovascular conditions............................................................................................................42
Colic/Diarrhoea conditions..........................................................................................................42
Qualitative Test for Tannins................................................................................................................43
Goldbeater's skin test.......................................................................................................................43
Ferric chloride (FeCl3) test..............................................................................................................43
Other methods.................................................................................................................................43
Hide-powder method.......................................................................................................................43
Stiasny's method..............................................................................................................................43
References...........................................................................................................................................44
Abstract
Nature is a unique source of structures of high stereo chemical diversity, many of them
possessing interesting biological activities and medicinal properties. In the context of the
worldwide spread of deadly conditions such as AIDS and a variety of cancers, an intensive
search for new lead compounds for the development of novel pharmacological therapeutics is
3
extremely important. The fact that the biological activity of tannin-containing plant extracts
has been known for ages has led, especially during the last two decades, to the isolation and
characterization of many representatives of this class. The group of unambiguously
characterized tannins includes more than 1000 natural products. In extensive biological tests
many representatives of the tannins exhibited antiviral and antibacterial properties, but
especially prominent was the antitumor activity. Certain tannins, for example, are able to
inhibit HIV replication selectively.
This assignment is aimed at expanding the students chemical knowledge on the need to
actually cherish our natural endowment especially plants and also to put into documentation
what tannin are actually.
Acknowledgement
We would like to gratefully and sincerely thank Professor Adamu for his guidance,
understanding, patience, friendship and most importantly for giving us the opportunity to
develop ourselves as regards to this research work.
Sir, your mentorship was paramount in providing a well-rounded experience consistent our
long-term career goals.
With this, you have encouraged us to not only grow as an experimentalist and a chemist but
also as an instructor, an independent thinker and a researcher. We are not sure many graduate
students are given the opportunity to develop their own individuality and self-sufficiency by
being allowed to work with such independence. Thank you Prof.
Introduction
The name ‘tannin’ is derived from the French ‘tanin’ (tanning substance) and is used for a
range of natural polyphenols.
4
Since ancient times it is known that certain organic substances have tanning properties and
are able to tan animal skins to form leather. Prehistoric tribes already knew about the tanning
of protective animal hides with brain material and the fat of the killed animals.2 However,
precisely what happens to the skin during the tanning process was only elucidated during the
twentieth century with the help of modern analytical techniques. the Real tanning is
understood as the crosslinking of the skin’s collagen chains, while false tanning entails filling
of hollow spaces between the skin’s collagen chains. The traditional tanning of animal skins
by means of plant tannins has been replaced gradually by mineral tanning, as represented by
alum tanning (or glacé tanning, a variant of alum tanning) and more recently, since the end of
the nineteenth century, by chromium tanning. In nature the tannins are found worldwide in
many different families of the higher plants such as in chestnut and oak wood, Divi-Divi,
Sumach, Myrobalaen, Trillo, Valonea or plant galls; depending on their origin, their
chemistry varies widely, having a molar mass of up to 20000 D.
High tannin concentrations are found in nearly every part of the plant, such as in the bark,
wood, leaves, fruit, roots, and seed. Frequently an increased tannin production can be
associated with some sickness of the plant. Therefore, it is assumed that the biological role in
the plant of many types of tannin is related to protection against infection, insects, or animal
herbivory. The tannins appear as light yellow or white amorphous powdnfers or shiny, nearly
colourless, loose masses, with a characteristic strange smell and astringent taste.
The tannins are applied widely, with uses ranging from tanning, known over millennia
(Mediterranean since ca. 1500 BC), through medicinal uses to uses in the food industry. In
medicine, especially in Asian (Japanese and Chinese) natural healing, the tannin-
containing plant extracts are used as astringents, against diarrhoea, as diuretics, against
stomach and duodenal tumours, and as anti-inflammatory, antiseptic, and haemostatic
pharmaceuticals. As tannins can precipitate heavy metals and alkaloids (except morphine),
they can be used in poisonings with these substances. It is also becoming clear that tannins
often are the active principles of plant-based medicines.
Tannins are used in the dyestuff industry as caustics for cationic dyes (tannin dyes), and also
in the production of inks (iron gallate ink). In the food industry tannins are used to clarify
wine, beer, and fruit juices. Other industrial uses of tannins include textile dyes, as
antioxidants in the fruit juice, beer, and wine industries, and as coagulants in rubber
production. Recently the tannins have attracted scientific interest, especially due to the
increased incidence of deadly illnesses such as AIDS and various cancers. The search for new
lead compounds for the development of novel pharmaceuticals has become increasingly
5
important; especially as the biological action of tannin containing plant extracts has been well
documented. During the last twenty years many representatives of this class of compounds
have been isolated and characterized.
Currently known tannins with unambiguously determined structures already number far more
than 1000 natural products. In extensive biological tests many representatives of this class
were found to have antiviral, antibacterial, and, especially, antitumor activity. For example,
certain tannins can selectively inhibit HIV replication.
The nomenclature of the tannins is full of misunderstanding, erroneous interpretations, and
changes caused by advances in this field. Not all tanning substances can be called tannins,
and on the other hand many types of tannin do not possess tanning properties but are counted
with the tannins because of their structural characteristics.
So what are tannins?
Bate-Smith and Swain defined the plant tannins as water soluble phenolic compounds with a
molar mass between 300 and 3000, showing the usual phenol reactions (e.g. blue colour with
iron(iii) chloride), and precipitating alkaloids, gelatins and other proteins. However, this
definition does not include all tannins, since, more recently, molecules with a molar mass of
up to 20000 D have been isolated that should also be classified as tannins on the basis of their
molecular structures.
Griffith defined tannins as “macromolecular phenolic substances” and divided them in two
major groups, the ‘hydrolysable’ and ‘condensed’ tannins. This definition of the tannins
ignores the low molecular and monomeric tannins with a molar mass below 1000 D.
Haslam classified the plant polyphenols into two broad structural themes:
(i) Galloyl and hexahydroxydiphenoyl esters and their derivatives.
(ii) (ii) Condensed proanthocyanidins.
Galloyl and hexahydroxydiphenoyl esters and their derivatives have been further classified
into several broad categories:
(1) Simple esters. (2) Depside metabolites (syn-gallotannins). (3) Hexahydroxydiphenoyl and
dehydrohexahydroxydiphenoyl esters (syn-ellagitannins) based upon: (a) 4C1 conformation of
D-glucose; (b) 1C4 conformation of D-glucose; (c) ‘open-chain’ derivatives of D-glucose. (4)
‘Dimers’ and ‘higher oligomers’ formed by oxidative coupling of ‘monomers principally
those of class (3) above. While in Haslam’s article, complex tannins have not been
mentioned, in the newly published review by Ferreira et al. only two classes of tannins,
namely: (i) condensed tannins and (ii) complex tannins are treated exhaustively.
6
Gross adopted the classical definition of tannins that was formulated by Freudenberg in 1920
cited therein.
According to Freudenberg and Gross tannins are usually divided into the flavonoid derived
condensed tannins, and into hydrolysable tannins. The former are divided into two groups,
namely: (i) gallotannins, which include also meta-depsids, and (ii) ellagitannins. Also, the
definition of tannins as a mixture of ‘flavolanes of varying structure’ at best only covers
some tannins and does not include the hydrolysable tannins which form a considerable
portion of the tannins. An organic chemistry textbook87 defines tannins as: “C- and O-
glycosidic derivatives of gallic acid (3,4,5-trihydroxybenzoic acid)”. This definition also
describes only some of the tannins and does not include the condensed tannins based on
flavan-3-ol (catechin) units. It is therefore necessary, as a result of the recently greatly
expanded structural range of the tannins, to formulate a definition that includes all tannins.
Tannins are polyphenolic secondary metabolites of higher plants. Corresponding
polyphenolic natural products have not yet been isolated from lower plants such as algae, or
from the animal kingdom. The polyphenolic structure of the secondary metabolites from
higher plants is a necessary but not sufficient requirement for membership of the tannin class.
When the structural characteristics of the currently known tannins are analysed, the relatively
low occurrence of C- and/or O glycosidic derivatives of gallic acid is noteworthy. However,
the characterized tannin structures show that, apart from the galloyl glycosides, the galloyl
residues can be linked to each other or to other residues through their aromatic carbon and/or
phenolic oxygen atoms. By these and similar couplings of two or more natural products to
each other, nature provides a nearly inexhaustible store of highly diverse structures. It should
be mentioned, however, that not all tannins must necessarily contain a galloyl unit or
derivative. Examples of this type are found in the so-called condensed tannins that are built
up from flavanoid precursors. The condensed tannins, constructed from at least two linked
catechin units (C-4 with C-8 or with C-6, see Fig. 1 below, compound 4), can alternatively be
linked through the hydroxy group of C-3 of each catechin unit to a galloyl unit.
Classification of the tannins based on their structural properties
Due to the enormous structural diversity of the tannins a systematic classification system
based on specific structural characteristics and chemical properties would provide a
convenient framework for further study. The observation that many tannins can be
7
fractionated hydrolytically into their components, for example by treatment with hot water or
with tannases, led to the classification of such tannins as ‘hydrolysable tannins’. Non
hydrolysable oligomeric and polymeric proanthocyanidins were classified as condensed
tannins. Therefore, the term ‘hydrolysable tannins’ includes both the gallotannins and the
ellagitannins. It should also be mentioned here that there are ellagitannins that are not
hydrolysable, because of a further C–C coupling of their polyphenollic residue with the
polyol unit, but are nevertheless for historical reasons classified as hydrolysable tannins [see
Fig. 6, vescalagin].
In 1985 the first tannins were described that contained, in addition to the
hexahydroxydiphenoyl (HHDP) units (the characteristic structural element of the monomeric
ellagitannins), also C-glycosidic catechin units [see Fig. 9, acutissimin A (76).These tannins
were originally classified as ‘non-classified tannins’, because they are only partially
hydrolysable due to the C–C coupling of their catechin unit with the glycosidic part. To
properly place these ‘non-classified tannins’ in some scheme, the terms ‘complex tannins’
and flavanoellagitannins were established over the following years. These examples clearly
show that the division of the tannins into two groups, viz. hydrolysable and non-hydrolysable
or condensed tannins cannot do justice to the structural diversity of the tannins. The terms
‘flavanotannins’ or ‘condensed flavonoid tanning substances’ that are occasionally found in
the literature denote tannins consisting of catechin units. The polymeric flavanotannins,
constructed from coupled flavan-3-ol (catechin) units, belong to the condensed tannins
(oligomeric and polymeric proanthocyanidins).
8
Fig.1 Classification of Tannins
On the basis of their structural characteristics it is therefore possible to divide the tannins into
four major groups: Gallotannins, ellagitannins, complex tannins, and condensed tannins (Fig.
1).
I. Gallotannins are all those tannins, in which galloyl units or their meta-depsidic
derivatives are bound to diverse polyol-, catechin-, or triterpenoid units.
II. Ellagitannins are those tannins in which at least two galloyl units are C–C coupled to
each other, and do not contain a glycosidically linked catechin unit.
III. Complex tannins are tannins in which a catechin unit is bound glycosidically to a
gallotannin or an ellagitannin unit.
IV. Condensed tannins are all oligomeric and polymeric proanthocyanidins formed by
linkage of C-4 of one catechin with C-8 or C-6 of the next monomeric catechin.
Different polyol units of the tannins
The standard metabolism for the biosynthesis of tannins in higher plants uses various
building blocks that are coupled to each other. For example, the gallotannins are
biosynthesized by the different coupling possibilities of a polyphenolic building block such
as gallic acid with diverse polyols such as D-glucopyranose. A complete listing of the
structures of all known tannins falls outside the scope of this article; however, the structures
of the currently known tannins are summarized by way of a fractionation of their
9
components. The following are some of the polyalcoholic components of the tannins: D-
Glucopyranose (5), D-hamamelose (6), sucrose (7),92 shikimic acid (8), quinic acid (9),
scyllo-quercitol (10) 93 and protoquercitol (11),94 salicin or 2-hydroxymethylphenyl β-D-
glucopyranoside (12),95 D fructopyranose (13), 6-cinnamoyl-D- glucopyranose (14), 1,5-
anhydro-D-glucitol,96 3,5-dihydroxyphenyl β-D-glucopyranoside (15),97 2-coumaroyl-D-
glucopyranose (16), 4-hydroxy-2-methoxyphenyl β-D-glucopyranoside (19),98 4-hydroxy-3-
methoxyphenyl β-D-glucopyranoside (20),98 3,4,5-trimethoxyphenyl β-D-glucopyranoside
(21),98 2,6 dimethoxy-4-hydroxyphenyl β-D-glucopyranoside (22),98 4-carboxy-2,6-
dihydroxyphenyl β-D-glucopyranoside (23),99 3-carboxy-5,6-dihydroxyphenyl β-D-
glucopyranoside (24),99
4-(3-oxobutyl)phenyl β-D-glucopyranoside (25),99 triterpenoid 26,77,78 salidroside
(27),89,92,100 methyl β-D-glucopyranoside (28),92 maclurin C-β-D-glucopyranoside
(29),92 maclurin 2_-O- ( p-hydroxybenzoyl)-C-β-D-glucopyranoside (30),92 mangiferin C-
β-D-glucopyranoside (31),92 iriflophenone C-β-D-glucopyranoside (32),101 isomangiferin
C-β-D-glucopyranoside (33),92 D-gluconic acid (34),15 D-glucitol (35),89 glycerol (36),
glycosidically bound Catechins 37, Catechins, epicatechins, gallocatechins, and
epigallocatechins 3880,88 etc. (Fig. 2). The hydroxy functions of the tannin polyol residues
may be linked fully or only partly with galloyl units or their derivatives, in which case they
may be linked to several other residues.3, 4, 77, 78. the diversity of tannin structures is
further enriched by the capability of the anomeric centre of the glycosidic components
to form C- and/or O-glycosidic, ester or acetal bonds, in the β or α form with a great variety
of building blocks.
Different galloyl derivatives of gallotannins, ellagitannins, and complex tannins
In many tannins two galloyl units are linked to each other through their aromatic carbon
atoms to form an axially chiral hexahydroxydiphenoyl (HHDP) unit (39, 40), which is the
characteristic structural element of the monomeric ellagitannins. Linking the galloyl unit of
the tannins, for instance via the phenolic oxygen atom, to a further galloyl unit leads to
formation of a meta-digalloyl unit (50), the characteristic structural element of the meta-
depsides which are also reckoned with the gallotannins.
Other important galloyl derivatives found in many types of tannin are: HHDP (39, 40),
flavogallonyl (41), valoneoyl (Val) (42), sanguisorboyl (San) (43),
10
Dehydrohexahydroxydiphenoyl (DHHDP) (44, 45 and 46), and gallagyl (Gal) (47),
elaeocarpusoyl (Ela) (48), dehydrodigalloyl (49), meta-digalloyl (50), chebuloyl.
Fig. 2 Polyol residues of Tannin
11
Different Galloyl units of Tannins
(Che) (51), trilloyl (52), dehydrochebuloyl (DHChe) (53), brevifolyl (54) etc. (Fig.
3).3,4,77,78,104–106
Single tannin classes
For clarity the four major groups of the tannins are briefly discussed by way of some selected
examples.
12
Gallotannins
Gallotannins are the simplest hydrolysable tannins, containing a polyphenolic and a polyol
residue. Although a great variety of polyol residues are possible, most of the gallotannins
isolated from plants contain a polyol residue derived from D-glucose. The hydroxy functions
of the polyol residues may be partly or fully substituted with galloyl units. In the case of
partial substitution with galloyl residues the remaining hydroxy groups may be either
unsubstituted or substituted with various other residues. For example, the anomeric centre of
the glycosidic residues of the gallotannins may be unsubstituted (α,β mixture) or substituted,
in α or β form, as ester or acetal. The metadepsides (or ‘syn-gallotannins’) 10 also belong to
the gallotannin group. Their galloyl residues are esterified with the polyol residue and also
with one or more linked galloyl units in the meta position relative to the galloyl units’
carboxyl groups. The gallotannins 2,3,4,6-tetra-O-galloyl-D-glucopyranose (TGG) (55) and
1,2,3,4,6-penta-O-galloyl-β--glucopyranose (β-PGG) (56), found in many plant families,
are key intermediates in the biosynthesis of nearly all hydrolysable plant polyphenols.107–
110 Gallotannins in which the polyol residues are coupled to cinnamoyl (17) or coumaroyl
(18) groups (e.g. 57 and 58) are relatively scarce.97,102,103 Most of the gallotannins
substituted with a galloyl unit at the anomeric centre of their D-glucosyl unit have the β
configuration at the anomeric centre. There are, however, also some natural products such as
1,4-di-O-galloyl-α-D-glucopyranose (59),17 where the anomeric centre of the D
glucopyranose has the α configuration.111–113 The structural diversity of the gallotannins is
demonstrated by some selected examples (Fig. 4).
13
Fig 4 Structure of some of the gallotannins
14
Fig. 5 Some of the coupling possibilities of D-glucopyranose in the 1C4 or 4C1
conformation with (R)- or (S)-configured HHDP units.
Ellagitannins
With more than 500 natural products characterized so far, the ellagitannins form by far the
largest group of known tannins.114 Ellagitannins are formed from the gallotannins by the
oxidative coupling of at least two galloyl units (62) (Figs. 4 and 5), yielding an axially chiral
HHDP unit (39 or 40). The chirality is caused on the one hand by the bulky ortho substituents
to the biaryl axis, and on the other hand by the atropisomerism caused by the inhibition of
free rotation around the axis. This is caused by the esterification of both ortho carboxy
groups
with the polyol (usually D-glucopyranose, Fig. 3).3,4,77,78,104–106 Remarkably, all
ellagitannins with HHDP units linked via the 4,6 or the 2,3-positions of their -glucosyl unit
15
have an (S)- configured HHDP unit, while linkage via the 3,6-positions seems to lead only to
an (R)-configured HHDP unit.77,78,115.
Esterification to other positions of the sugar molecule, for example a 1,6-coupling 20,74 is
rarely found in nature. In the majority of ellagitannins with an axially chiral glucose-bound
HHDP unit, both the configuration of the biaryl unit and the conformation of the D-glucosyl
unit are determined by their linkage positions. An HHDP unit bound to the 2,3- or 4,6- or
1,6-positions of D-glucopyranose in the natural products always has the (S)-configuration,
while most 2,4- or 3,6- coupled HHDP units favour the (R)-configuration. Thermodynamics
govern the resulting D-glucose conformation, which again is determined by the coupling
positions of the HHDP unit to the glucopyranose ring. While the glucopyranosyl
16
Fig. 6 Typical ellagitannins with a C-glycosidic bond 77,78 and with a D-
gluconic acid unit.
Fig. 7 The structure of a rare ellagitannin with a triterpenoid structural unit, and of a rare α-
configured ellagitannin.
assumes a 4C1 conformation in the case of 2,3- or 4,6-HHDP coupling, a 1,6- or 3,6- or 2,4-
HHDP coupling always favours the thermodynamically less stable 1C4 conformation (Fig.
5). For both the C-glycosidic ellagitannins and the ellagitannins with a D-gluconic acid unit
the coupling of the HHDP unit via the 2,3- and 4,6-positions of the D-glucosyl is highly
characteristic. The C-glycosidic bond between the open-chain sugar and the bidentate
substituent is always formed at C-1 of the sugar. Typical examples of these groups of
substances are vescalagin (70) 77,78 with a C-glycosidic bond, and lagerstannin C (71) 15
with a D-gluconic acid unit (Fig. 6). Seemingly, for the routine biosynthesis of the tannins,
nature does not use only D-glucopyranose for the esterification with gallic acid. For example,
D-hamamelose (6) and complex triterpenoids such as 26 are also used in tannin biosynthesis.
17
As example of an ellagitannin with a triterpenoid structural unit, which could be isolated only
seldomly from natural sources, the natural product castanopsiniin A (72) 77,78 can be
mentioned. Also, the ellagitannin group contains few examples where the anomeric centre of
D-glucopyranose has the α-configuration. Heterophylliin A (73) 36 is one of the rare
examples of this type
(Fig. 7).
Fig 8 the structures of punicalin (74) and terflavin B (75).
18
As early as 1977 Mayer et al. published the isolation of the ellagitannin punicalin (74) from
the fruit husks of Punica granatum L.116 However, the correct structure was published only
in 1986 by Nishioka et al.24 Punicalin [4,6-(S,S)-gallagyl- D-glucopyranose] (74) contains
the so-called gallagyl unit as characteristic structural element. The gallagyl unit itself
is constructed from a lactonized HHDP nucleus which is C–C coupled with two galloyl
(3,4,5-trihydroxybenzoyl) residues.21 The punicalin structure is completed with a D-
Glucosyl unit which is linked via two hydrolytically cleavable ester bridges to the gallagyl
building block. Little is known about the biosynthesis of punicalin (74). It is known,
however, that terflavin B (75), also isolated from Punica granatum L., is a key intermediate
in the biosynthesis. Terflavin B can be transformed directly into punicalin (74) by oxidative
coupling (Fig. 8).21,117
Complex tannins
The structures of the complex tannins are built up from a gallotannin 43 unit or an
ellagitannin 91 unit, and a catechin unit.4,77,78,91 One example from this substance class is
acutissimin A (76), having a flavogallonyl unit (nonahydroxytriphenoyl unit) bound
glucosidically to C-1, and linked via three further hydrolysable ester bridges to the D-glucose
derived polyol (Fig. 9).77,78
Condensed tannins
One of the striking properties of the monomeric catechins and leukoanthocyanidins, that have
no tanning properties, is their ability to be converted into oligomers and polymers that do
have tanning properties, by the action of acids or enzymes.3,4,77,78,88,91,118 Condensed
tannins are oligomeric and polymeric proanthocyanidins consisting of coupled flavan-3-ol
(catechin) units (oligomeric or polymeric proanthocyanidins = condensed proanthocyanidins
= condensed tannins). Biosynthetically the condensed tannins are formed by the successive
condensation of the single building blocks, with a degree of polymerization between two and
greater than fifty blocks being reached. The coupling pattern of the catechin units in
condensed tannins can vary considerably. For example, many con densed tannins are known
where the coupling of the single units is by way of position C-4 of the first unit linked with
C-8 (or C-6) 4,119 of the second unit, which may have a different substitution pattern.4,120
The tannins found in red wine (and to a lesser extent in white wine) are this type of
condensed tannins.
The properties of these tannins, and especially their importance to winemaking, depend on
their specific reaction with proteins, which in turn is directly related to their degree of
19
polymerization. Oligomers and polymers consisting of two to ten catechin units are also
known as flavolans.11 Some typical condensed tannins with unsubstituted catechin units are
procyanidin B2 [epicatechin-(4β 8)-epicatechin (77)], proanthocyanidin A1 [epicatechin- (4β
8,2β O 7)-catechin (78)], proanthocyanidins A2 [epicatechin-(4β 8,2β O 7)-epicatechin (79)],
and proanthocyanidin C1 [epicatechin-(4β 8)-epicatechin- (4β 8)-epicatechin (80)] (Fig. 10).
Fig. 9 Acutissimin A, the usual representative of the complex tannins.77,78
20
Fig. 10 Different linkage patterns of condensed tannins, for example procyanidin B2 (77),
proanthocyanidin A1 (78), proanthocyanidin A2 (79) (79) and proanthocyanidin C1 (80).
21
Plants containing Tannins
From literature, I can gallantly conclude that all plants contains tannin but the only different
lies in the percentage yield from any plants.
1. Aloe Vera (Aloe barbadensis Miller}
Structures of some of the active compounds in the plant
The aloe vera plant is often found near water in sand or rocks. It has thick stiff leaves and
slender, orange-colored flower spikes. The gel found in the leaves is commonly used to speed
22
the healing of skin conditions, including burns and wounds. The sap found in the base of the
leaf is used as a digestive stimulant and a strong laxative.
Medicinal Uses
Aloe Helps with Digestion
Poor digestion is related to many diseases. A properly functioning digestive tract is one of the keys and foundations of health. Aloe is known to soothe and cleanse the digestive tract and help improve digestion. The interesting thing about taking aloe internally is that, because it is an adaptogen, it helps with either constipation or diarrhea, helping to regulate your elimination cycles in whatever way you need. It’s been a great remedy for people with problems such as irritable bowel syndrome as well as acid reflux. Aloe also helps to decrease the amount of unfriendly bacteria and in our gut keeping your healthy intestinal flora in balance. Aloe is also a vermifuge, which means it helps to rid the body of intestinal worms.
1. Aloe Helps in Detoxification
Aloe Vera is a gelatinous plant food, just like seaweeds and chia seeds. The main benefit to consuming gelatinous plant foods in your diet is that these gels move through the intestinal tract absorbing toxins along the way and get eliminated through the colon. This will help the proper elimination of waste from your body and help the detoxification of your body.
2. Aloe Alkalizes the Body
Disease cannot manifest in an alkaline environment. Most people are living and subsisting on mostly acidic foods. For great health, remember the 80/20 rule – 80% alkaline forming foods and 20% acidic. Aloe vera is an alkaline forming food. It alkalizes the body, helping to balance overly acidic dietary habits.
3. Cardiovascular Health
There hasn’t been a lot of studies conducted on aloe’s effect on cardiovascular health, but there has been some research to show that aloe vera extract injected into the blood, greatly multiplies the oxygen transportation and diffusion capabilities of the red blood cells. According to a study published in the 2000 issue of the British Medical Journal, beta sitosterol helps to lower cholesterol. By regulating blood pressure, improving circulation and oxidation of the blood, lowering cholesterol, and making blood less sticky, aloe vera juice may be able to help lower the risk of heart disease.
4. Aloe Helps Boost the Immune System
I think given the stresses of our daily lives, every one can use a boost to their immune systems. The polysaccharides in aloe vera juice stimulate macrophages, which are the white blood cells of your immune system that fight against viruses. Aloe is also an immune enhancer because of its high level of anti-oxidants, which help combat the unstable compounds known as free-radicals, contributing to the aging process. (Free radicals are a bi-product of life itself, it is a naturally occurring process but we can overload ourselves with
23
unnecessary free-radicals by living an unhealthy lifestyle). Aloe is also an antipyretic which means it used to reduce or prevent fever.
5. Aloe Vera is Great for the Skin
Because of aloe’s well-known healing properties for the skin, aloe is one of the primary compounds used in the cosmetic industry. It is a known vulnerary, (meaning it helps heal wounds) and is great for applying topically to burns, abrasions, psoriasis and even to bug bites. Aloe acts as an analgesic, acting to help relieve pain of wounds. It’s feels especially good to cut a stem of aloe, place it in the fridge and rub it on sun burnt skin – the immediate soothing effect feels like an absolute lifesaver. Aloe is also an antipruritic: A substance that relieves or prevents itching. Aloe vera is an astringent: which causes the contraction of body tissues, typically used to reduce bleeding from minor abrasions. Due to aloe’s high water content (over 99% water) it is a great way to hydrate, moisturize and rejuvenate the skin and fits within my general guideline: “Don’t put anything on your skin that you wouldn’t eat!” Aloe increases the elasticity of the skin making it more flexible through collagen and elastin repair. Aloe is an emollient, helping to soften and soothe the skin. It helps supply oxygen to the skin cells, increasing the strength and synthesis of skin tissue and induces improved blood flow to the skin through capillary dilation.
Traditional uses 1. Aloe vera gel is used as an ingredient in commercially available lotion, yogurt,
beverages and some desserts. 2. Aloe vera gel is used for consumption and relief of digestive issues such as heart
burn and irritable bowel syndrome. 3. It is common practice for cosmetic companies to add sap or other derivatives from
Aloe vera to products such as make up, tissues, moisturizers, soaps, sunscreens, incense, razors and shampoos.
4. Other uses for extracts of Aloe vera include the dilution of semen for the artificial fertilization of sheep, use as fresh food preservative, and use in water conservation in small farms.
5. Aloe vera has a long association with herbal medicine, although it is not known when its medical applications were first discovered. Aloe vera is non-toxic, with no known side effects, provided the aloin has been removed by processing. Taking Aloe vera that contains aloin in excess amounts has been associated with various side effects. However, the species is used widely in the traditional herbal medicine of China, Japan, Russia, South Africa, The United States, Jamaica and India. Aloe vera is alleged to be effective in treatment of wounds.
The big leaves contain sap, which works amazingly against:
Burns
Wounds and cuts
Eczema
Skin allergies
24
The intake of aloe vera juice can heal:
digestive problems and appetite
Chronic constipation
ulcerative colitis
2. Tea Tree (Melaleuca alternifolia}
Structures of some of the active compound in the plant
25
This shrub is generally found in swamps and contains tiny green leaves and wispy white
flowers. The essential oils taken from this plant are a popular antiseptic used for stings,
burns, wounds and many other skin conditions. Tea trees are also utilized for stimulating the
immune system and for helping to treat chronic fatigue syndrome.
Medicinal Uses1. Bad breath. Early research shows that adding tea tree oil to an essential oil
mixture containing peppermint and lemon oils can reduce bad breath. 2. Cold sores (Herpes labialis). Research so far suggests that applying 6% tea
tree oil gel 5 times daily does not significantly improve cold sores. 3. Eyelid infection (blepharitis). Early research shows that tea tree might cure
common eyelid infections and reduce the associated symptoms, including eye inflammation and vision loss.
4. Dandruff. Early research suggests that applying a 5% teat tree oil shampoo three minutes daily for four weeks reduces scalp lesions, scalp itchiness, and greasiness in patients with dandruff.
5. Dental plaque. Results from research examining the effects of tea tree oil on dental plaque are inconsistent. Some early research shows that brushing the teeth with a 2.5% tea tree oil gel twice daily for eight weeks reduces gum bleeding but not plaque in people who have gingivitis caused by plaque. Also, using a mouthwash containing tea tree oil after a professional teeth cleaning
26
does not seem to reduce plaque formation. However, rinsing with a specific product (Tebodont) containing tea tree oil and a chemical called xylitol does seem to reduce plaque.
6. Gingivitis. Results from research examining the effects of tea tree oil on gingivitis are inconsistent. Some early research shows that brushing the teeth with a 2.5% tea tree oil gel twice daily for eight weeks reduces gum bleeding but does not improve overall gum health in people who have gingivitis caused by plaque. However, rinsing with a specific product (Tebodont) containing tea tree oil and a chemical called xylitol seems to reduce gum inflammation.
Traditional uses
1. Tea Tree Oil for Acne
One of the most common uses for tea tree oil today is in skin care products, and it’s considered one of the home remedies for acne. One study found tea tree oil to be just as effective as benzoyl peroxide, but without the negative side effects of red and peeling skin.
You can make a tea tree oil acne face wash by mixing five drops of tea tree essential oil with two teaspoons of raw honey. Simply rub on your face, leave on for one minute, then rinse off.
2. Tea Tree Oil for Hair
Tea tree oil has proven very beneficial for the health of your hair and scalp. Like coconut oil for hair, tea tree oil has the ability to soothe dry flaking skin, dandruff and even can be used for the treatment of lice. To make homemade tea tree oil shampoo, mix it in with aloe vera gel, coconut milk nutrition and other essential oils like lavender oil.
3. Tea Tree Oil for Cleaning
Another fantastic way to use tea tree oil is as a household cleaner. Tea tree oil have powerful antimicrobial properties and can kill off bad bacteria in your home. To make homemade tea tree oil cleaner, mix with water, vinegar and lemon essential oil.
4. Tea Tree Oil for Psoriasis and Eczema
Tea tree oil can help relieve any type of skin inflammation, including being used as a natural eczema treatment and for psoriasis. Simply mix one teaspoon coconut oil, five drops of tea tree oil and five drops of lavender oil to make homemade tea tree oil eczema lotion or body soap. In addition, if you have eczema or psoriasis, you should consider going on the GAPS diet and supplementing with vitamin D3.
5. Tea Tree Oil for Toenail Fungus and Ringworm
Because of its ability to kill parasites and fungal infections, tea tree oil is a great choice to use on toenail fungus, athlete’s foot and ringworm. Put tea tree oil undiluted on the area and, for stubborn fungi, it can also be mixed with oil of oregano. Tea tree oil has also been proven beneficial for treating and removing warts, so simply put tea tree oil directly on the area for 30 days.
27
You must have heard about tea green a lot, especially for treatment against loss of hair and
headaches. It contains amazing benefits like antibacterial, anti-fungal and works best as
antiseptic. In addition, it treats:
Burns
Fever
Athlete foot
fatigue syndrome
Vaginal infections
Acne and warts
Insect bites
28
3. Lemon balm (Melissa Officinalis)
Structures of some of the active compounds in the plants
29
Medicinal uses
1. Sleep
In a 15 day open-label study in persons with mild to moderate stress and anxiety coupled with sleep disturbances, supplementation of Melissa officinalis (7% Rosmarinic acid and 15% total hydrocinnamic acids) taking 300mg at breakfast and again before sleep (600mg total) noted reductions in anxiety-related insomnia by 42% (Overall).[25]
Melissa officinalis is commonly consumed alongside Valeriana officinalis for the purpose of sedation, and at least one multicenter study using both in a combination noted that the supplement group (120mg Valerian (4.5:1 concentration) and Lemon Balm at 80mg (5:1 concentration) taken thrice before bed) after 30 days reported enhanced sleep quality (33% of respondents reported better sleep) which was greater than placebo (9% of the placebo group reported better sleep); treatment was very well tolerated with no significant side effects.[1] One other trial has noted that this combination was effective in reducing restlessness and dyssomnia in children.[2]
Appears to have sedative properties and promote sleep quality, but there is relatively little evidence to support it as two well controlled studies are confounded with the inclusion of Valerian
2. Anxiety and Stress
In rats given Melissa officinalis extract (9.32% Rosmarinic Acid) at 120-360mg/kg bodyweight for 15 days appeared to have anxiolytic effects in an open field test as well as an elevated maze test but not in a four-hole board test at the higher two doses (240mg/kg and 360mg/kg).[26] The anxiolyic effects (30-300mg/kg ethanolic extract) have in one study been comparable to 1mg/kg Diazepam when dosed over 10 days, and appeared to be more effective in females (with only 300mg/kg being statistically significant in males, but all doses being effective in female rats).[27]
One study has noted that inhalation of lemon oil vapor has exerted anti-stress responses, and that these effects were related to serotonergic signalling (particularly the receptor 5-HT1A).[28]
Two animal studies suggest anxiety reducing effects of oral Lemon Balm, with one noting that lemon vapor was also effective
In a clinical setting, an acute dose of 300 or 600mg Melissa officinalis prior to an acute stress test (DISS battery of tests[29] followed with Mood assessment via Bond and Lader VAS mood scales[30]) noted that the higher dose was associated with improved self-reported calmness, reduced alertness (increased after test) following the test while the 300mg dose failed to significantly modulate mood.[31] Another acute study noted that a Lozenge containing Melissa officinalis was able to induce brain wave alterations similar to that of standard anxiolytics.[32]
Can reduce anxiety when dosed acutely (single dose taken before stressor)
In humans consuming 300mg Melissa officinalis (7% Rosmarinic acid and 15% total hydrocinnamic acids) at breakfast and again before sleep for 15 days in an open-label trial,
30
there appears to be general anxiolytic propeties in regards to anxiety-related eating problems (33% lower than baseline), emotional instability (7%), fatigue (18%), feelings of guilt (15%) or inferiority (18%), psychosomatic symptoms (33%) and intellectual disturbance (28%).[25]
Appears to reduce anxiety when taken over a period of time in humans (morning and nightly doses)
3. Memory and Learning
One study has noted that Melissa officinalis have nicotinic receptor binding properties[33] as well as muscarinic.[34] One study has noted weak acetylcholinesterase inhibiting property with fresh, but not dried, leaves of Lemon Balm;[33] a subsequent study failed to replicated acetylcholinesterase inhibiting properties up to 0.25mg/mL.[6]
Subsequently, a study conducted noting incubation with Melissa officinalis noted that the extract had little ability to displace either Nicotine or scopolamine from the receptor.[35] This was followed up on in post-mortem human neural tissue where nicotine was displaced at moderate concentrations of 180-3120µg/mL and scopolamine at 2.69-4.31mg/mL (ethanolic herb extract) although it could be extracted into more effective fractions (the most potent noted fractions being 4.2µg/mL nicotine displacement and 102.6µg/mL for scopolamine) although there still appears to be a large degree of variability.[6]
Appears to interact with acetylcholine receptors, there appears to be some agonistic (activating) properties that are very volatile (not reliable); if looking at solely the most effective fragments, the affinity at least appears respectable
In the hippocampal dentate gyrus of aged rats, Melissa officinalis at 50-200mg/kg daily was able to enhance neurogenesis (244.1-763.9% of control group, respectively) which was associated with reduced corticosterone concentrations.[24]
Has been noted to enhance neurogenesis in at least one rat study giving oral administration
300mg Melissa officinalis given prior to an acute stress test was noted to be (nonsignificantly) associated with improved answering on mathematical questions; increasing the dose to 600mg did not help in reaching statistical significance.[31]
Following ingestion of 600mg or 1600mg Melissa officinalis acutely, improvements relative to placebo are noted in quality of memory (percentage of answers or recollections that are correct) only with trends for improvement (not significant) were noted in picture-recall, delayed word recall, spatial memory and no influence was noted on working memory nor attention in this study, and self-reported attention was similar.[6] Sporadic improvements in memory quality (digital vigilance accuracy and choice reaction time accuracy) have been noted elsewhere.[35]
There appears to be comparatively weak cognitive enhancing properties assocaited with oral Melissa officinalis supplementation at higher doses (600-1600mg)
For cognitive parameters sometimes seen as adverse, 600-1600mg Melissa officinalis has been noted to reduce the speed of memory without influencing memory formation per se.[6] A
31
reduction in rapid visual information processing has also been noted, with sporadic influences on false-positive processing (neither 600 nor 1600mg, but 1000mg, being associated with increased false-positives).[6] Another study to record spatial memory found a statistically significant reduction thereof following 300-900mg acute ingestion, this reduction was also noted for word recollection.[35]
The calming effects of Melissa officinalis may also reduce the speed of learning, possibly secondary to being slightly sedative or too 'calming'
4. Neuroprotection
In hippocampal corticol neurons deprived of oxygen, 10μg/mL Lemon Balm was associated with preserving roughly half of corticol neurons that would have been lost to hypoxia and also reduced concentrations of caspase-3 and DNA fragmentation (both indicative of apoptosis); concentrations of 200-500μg/mL showed inherent cytotoxicity to neurons.[4] Neuroprotection has also been noted in hippocampal cells exposed to ecstasy.[36]
Appears to have neuroprotective effects in vitro in pro-oxidative toxicity
In a model of hippocampal occlusion (mice) given 100mg/kg Lemon Balm for 2 weeks prior to occlusion treatment and continued thereafter noted reduced lipid peroxidation (MDA and TEAC) and the concentrations of HIF-1α, TNF-α and IL1-β (all induced during hypoxia) were effectively suppressed by Melissa officinalis.[4]
This may extend to living models undergoing hypoxia (lack of oxygen) in neural tissue
5. Pain
One study has note dose-dependent pain-reducing effects of oral ingestion of Melissa officinalis (ID50 of 241.9mg/kg) in mice subject to a battery of tests (acetic acid writhing, glutamate, and formalin) which seems to be related to the Rosmarinic Acid content.[37]
May have pain relieving properties, requires more researches.
Traditional usesLemon balm is a perennial herb from the mint family. The leaves, which have a mild lemon aroma, are used to make medicine. Lemon balm is used alone or as part of various multi-herb combination products.
Lemon balm is used for digestive problems, including upset stomach, bloating, intestinal gas (flatulence), vomiting, and colic; for pain, including menstrual cramps, headache and toothache; and for mental disorders, including hysteria and melancholia.
Many people believe lemon balm has calming effects so they take it for anxiety, sleep problems, and restlessness. Lemon balm is also used for Alzheimer's disease, attention deficit-hyperactivity disorder (ADHD), an autoimmune disease involving the thyroid (Graves' disease), swollen airways, rapid heartbeat due to nervousness, high blood pressure, sores, tumors, and insect bites.
32
Lemon balm is inhaled as aromatherapy for Alzheimer's disease.
Some people apply lemon balm to their skin to treat cold sores (herpes labialis).
In foods and beverages, the extract and oil of lemon balm are used for flavoring.
The leaves of this plant have mint like smell and provides nourishing image. It has big
summer flowers, which can be rubbed against the skin for:
Animal bites
Mosquito bites
Sores
Herpes
The nectar that is used with water in form of juice is beneficial for:
Fevers
Colds and cough
Depression
Headaches
Upset stomach
Insomnia
4. Thyme (Thymus Vulgaris)
Some of the active compounds in the plant
33
Some of the active compounds in thymus vulgaris
Thyme is a fragrant herb that makes a wonderful addition to your cooking, in part because it
is rich in antioxidants. Thyme contains health-boosting flavonoids including apigenin,
naringenin, luteolin, and thymonin, and has been shown to protect and increase the
percentage of healthy fats found in cell membranes. As reported by the George Mateljan
Foundation:12 “In particular, the amount of DHA (docosahexaenoic acid, an omega-3 fatty
acid) in brain, kidney, and heart cell membranes was increased after dietary supplementation
with thyme.”
Thyme is also nutrient dense, containing vitamin C, vitamin A, iron, manganese, copper, and
dietary fiber. When used in cooked dishes, thyme may also help inhibit glycation and the
formation of dangerous advanced glycation end products (AGEs) in your food, making
thyme a potential preventer of heart disease and premature aging. Due to thyme oil’s
antibacterial, antispasmodic, antirheumatic, expectorant, hypertensive, and calming
properties, it also has a long list of topical uses, including:
Traditional uses of thyme
Home remedy – Thyme oil is used to relieve and treat problems like gout, arthritis,
wounds, bites, and sores, water retention, menstrual and menopausal problems,
nausea and fatigue, respiratory problems (like colds), skin conditions (oily skin and
scars), athlete’s foot, hangovers, and even depression.
Aromatherapy oil – The oil can be used to stimulate the mind, strengthen memory
and concentration, and calm the nerves.
34
Hair product – It is said that thyme oil can prevent hair loss. It is used as a treatment
for the scalp and is added to shampoos and other hair products.
Skin product – Thyme oil can help tone aged skin and prevent acne outbreaks.
Mouthwashes and herbal rinses – Like peppermint, wintergreen, and eucalyptus
oils, thyme oil is used to improve oral health.
Insecticide/insect repellent – Thyme oil can keep insects and parasites like
mosquitoes, fleas, lice, and moths away
Medicinal uses
Thyme has antiseptic qualities that make it useful for a mouthwash and to combat tooth
decay. Its antiseptic qualities also make it useful in cases of anemia, bronchial ailments, and
intestinal problems, as well as a skin cleanser. It has been known for anti-fungal properties
that can be used to treat athlete’s foot and has anti-parasitic properties that are useful against
lice, scabies, and crabs. It has shown useful for colic, excess gas, sore throats, and as a
hangover remedy. Thyme also proves beneficial as an expectorant to loosen and expel
mucous.
Make a poultice by mashing the leaves into a paste for use on skin inflammations and sores.
Using thyme for an anti-fungal or parasitic agent can be done by mixing four ounces of fresh
thyme to a pint of vodka or fresh vinegar with “the mother” still in the container (the mother
is the vinegar starter). Crush the thyme leaves slightly and let sit 12 hours or overnight. Or
buy the essential oil and use it sparingly. Apply to the affected area.
For gastric issues or bronchitis, make a tea of 1 teaspoon leaves to each cup of boiling water
and steep 10-15 minutes. Use only once a day. Add small amounts of honey to sweeten, if
desired.
Infusions of thyme have also been useful in soothing and healing muscle spasms and skin
irritations. Thyme also contains a compound that is helpful in preventing blood clots.
Aromatherapy of the essential oil of thyme has been used to boost the mind, body, and spirit.
Vapors of thyme’s essential oil have been effective for treating respiratory infections. Thyme
oil or infusion can be added to bath water to aid bronchial problems and sooth rheumatism.
35
Burning thyme can repel insects and a dilution of thyme oil can be used externally as a
deodorant and antiseptic that will prevent mildew. An ointment made with thyme has been
used to treat warts. And some have said that it is useful to help new mothers to expel the
afterbirth. Thyme ointment can be made from its leaves to sooth the discomfort associated
with gout and killing worms internally.
Thyme has many helpful actions. It has been used as an antiseptic, anodyne, disinfectant,
antitussive, anti-inflammatory, rubefacient, demulcent, apertif, carminative, diaphoretic,
depurative, digestive, diuretic, expectorant, fungicide, nervine, pectoral, sedative, stimulant,
and vermifuge.
As I previously mentioned, thyme oil is an effective natural agent against nasty bacterial
strains. A study9 presented at the Society for General Microbiology's spring conference in
Edinburgh pointed out that essential oils may be efficient and affordable alternatives to
antibiotics in the battle against resistant bacteria.
Among the essential oils tested, cinnamon oil and thyme oil were found to be the most
successful against various Staphylococcus species, including the dreaded MRSA.
Researchers said that this can help lower antibiotic use and minimize the formation of new
resistant strains of microorganisms.
Oil of thyme can also function as a decontaminant for food products. As shown in Food
Microbiology, both basil and thyme essential oils exhibited antimicrobial properties against
Shigella sonnei and Shigella flexneri that may contaminate food. The compounds thymol and
carvacrol in thyme oil demonstrated this benefit.10
Furthermore, thyme oil can be used as a preservative against spoilage and several foodborne
germs that can contribute to health problems. It is effective against other forms of bacteria
like Salmonella, Enterococcus, Escherichia, and Pseudomonas species.11
Other reports also show that oil of thyme has anti-inflammatory properties. In a research
published in the Journal of Lipid Research,12 six essential oils including thyme oil showed
the ability to suppress the inflammatory cyclooxygenase-2 (COX-2) enzyme in the same
manner as the antioxidant resveratrol does. It was noted that the chemical constituent
carvacrol was responsible for this effect.
36
The same study also noted that thyme and the other essential oils activated peroxisome
proliferator-activated receptors (PPARs), which help suppress COX-2 expression.
In addition to these, significant health benefits of thyme oil include:14
Helps reduce symptoms of chronic fatigue syndrome
Stimulates menstrual flow
Increases circulation and elevates low blood pressure
Triggers the removal of waste that may lead to cellulite
Eases nervousness and anxiety
Helps fight insomnia
Eliminates bad breath and body odor
37
6. Chamomile (Matricaria chamomilla L.)
38
Some of the secondary metabolites in the plant.
Chamomile is most popular in tea form for use to calm upset stomach and help
support restful sleep. Germany’s Commission E (a government organization) has
even approved the use of chamomile for reducing swelling on your skin and fighting
39
bacteria. Chamomile is a powerful anti-inflammatory that also has antibacterial, anti-
spasmodic, anti-allergenic, muscle relaxant, and sedative properties. It is used to treat
psoriasis, eczema, chickenpox, diaper rash, slow-healing wounds, abscesses, and gum
inflammation, and according to Herb Wisdom may also be useful for the following
conditions:
“The oil serves many medicinal purposes, but one of the best-documented uses is for
relaxation. The oil has a calming effect on people, and can be used to help induce
sleep, ease frayed nerves, and promote a general sense of calmness and well being. It
is great for those with nervousness or anxiety problems. Aside from having mental
calming properties, chamomile is also good at relaxing sore muscles and tight joints.
It can ease menstrual cramps and back aches, as well as relax the digestive system to
ease upset stomach or indigestion issues. When applied topically to the skin, it
soothes redness and irritation. For this reason, it is a common ingredient in skincare.
It also eliminates itchiness and is good for those with allergic reactions. Sometimes
chamomile is used on rashes. Because of its anti-inflammatory properties, it can work
to take down swelling caused by rashes or skin irritants.”
Traditional uses
Traditionally, chamomile has been used for centuries as an anti-inflammatory, antioxidant,
mild astringent and healing medicine . As a traditional medicine, it is used to treat wounds,
ulcers, eczema, gout, skin irritations, bruises, burns, canker sores, neuralgia, sciatica,
rheumatic pain, hemorrhoids, mastitis and other ailments. Externally, chamomile has been
used to treat diaper rash, cracked nipples, chicken pox, ear and eye infections, disorders of
the eyes including blocked tear ducts, conjunctivitis, nasal inflammation and poison ivy.
Chamomile is widely used to treat inflammations of the skin and mucous membranes, and for
various bacterial infections of the skin, oral cavity and gums, and respiratory tract.
Chamomile in the form of an aqueous extract has been frequently used as a mild sedative to
calm nerves and reduce anxiety, to treat hysteria, nightmares, insomnia and other sleep
problems. Chamomile has been valued as a digestive relaxant and has been used to treat
various gastrointestinal disturbances including flatulence, indigestion, diarrhea, anorexia,
motion sickness, nausea, and vomiting . Chamomile has also been used to treat colic, croup,
and fevers in children .It has been used as an emmenagogue and a uterine tonic in women. It
is also effective in arthritis, back pain, bedsores and stomach cramps.
40
Medicinal uses
Anti-inflammatory and antiphlogistic properties
The flowers of chamomile contain 1–2% volatile oils including alpha-bisabolol, alpha-
bisabolol oxides A & B, and matricin (usually converted to chamazulene and other
flavonoids which possess anti-inflammatory and antiphlogistic properties . A study in human
volunteers demonstrated that chamomile flavonoids and essential oils penetrate below the
skin surface into the deeper skin layers . This is important for their use as topical
antiphlogistic (anti-inflammatory) agents. One of chamomile’s anti-inflammatory activities
involve the inhibition of LPS-induced prostaglandin E(2) release and attenuation of
cyclooxygenase (COX-2) enzyme activity without affecting the constitutive form, COX-1 .
Anticancer activity
Most evaluations of tumor growth inhibition by chamomile involve studies with apigenin
which is one of the bioactive constituents of chamomile. Studies on preclinical models of
skin, prostate, breast and ovarian cancer have shown promising growth inhibitory effects .In a
recently conducted study, chamomile extracts were shown to cause minimal growth
inhibitory effects on normal cells, but showed significant reductions in cell viability in
various human cancer cell lines. Chamomile exposure induced apoptosis in cancer cells but
not in normal cells at similar doses .The efficacy of the novel agent TBS-101, a mixture of
seven standardized botanical extracts including chamomile has been recently tested. The
results confirm it to have a good safety profile with significant anticancer activities against
androgen-refractory human prostrate cancer PC-3 cells, both in vitro and in vivo situation .
Common cold
Common cold (acute viral nasopharyngitis) is the most common human disease. It is a mild
viral infectious disease of the upper respiratory system. Typically common cold is not life-
threatening, although its complications (such as pneumonia) can lead to death, if not properly
treated. Studies indicate that inhaling steam with chamomile extract has been helpful in
common cold symptoms; however, further research is needed to confirm these findings.
41
Cardiovascular conditions
It has been suggested that regular use of flavonoids consumed in food may reduce the risk of
death from coronary heart disease in elderly men . A study assessed the flavonoid intake of
805 men aged 65–84 years who were followed up for 5 years. Flavonoid intake (analyzed in
tertiles) was significantly inversely associated with mortality from coronary heart disease and
showed an inverse relation with incidence of myocardial infarction. In another study , on
twelve patients with cardiac disease who underwent cardiac catheterization, hemodynamic
measurements obtained prior to and 30 minutes after the oral ingestion of chamomile tea
exhibited a small but significant increase in the mean brachial artery pressure. No other
significant hemodynamic changes were observed after chamomile consumption. Ten of the
twelve patients fell into a deep sleep shortly after drinking the beverage. A large, well-
designed randomized controlled trial is needed to assess the potential value of chamomile in
improving cardiac health.
Colic/Diarrhoea conditions
An apple pectin-chamomile extract may help shorten the course of diarrhea in children as
well as relieve symptoms associated with the condition . Two clinical trials have evaluated
the efficacy of chamomile for the treatment of colic in children. Chamomile tea was
combined with other herbs (German chamomile, vervain, licorice, fennel, balm mint) for
administration. In a prospective, randomized, double-blind, placebo-controlled study, 68
healthy term infants who had colic (2 to 8 weeks old) received either herbal tea or placebo
(glucose, flavoring). Each infant was offered treatment with every bout of colic, up to 150
mL/dose, no more than three times a day. After 7 days of treatment, parents reported that the
tea eliminated the colic in 57% of the infants, whereas placebo was helpful in only 26%
(P<0.01). No adverse effects with regard to the number of nighttime awakenings were noted
in either group . Another study examined the effects of a chamomile extract and apple pectin
preparation in 79 children (age 0.5–5.5 y) with acute, non-complicated diarrhea who received
either the chamomile/pectin preparation (n = 39) or a placebo (n = 40) for 3 days. Diarrhea
ended sooner in children treated with chamomile and pectin (85%), than in the placebo group
(58%) . These results provide evidence that chamomile can be used safely to treat infant colic
disorders of chamomile in managing diabetes.
42
Qualitative Test for Tannins
There are three groups of methods for the analysis of tannins: precipitation of proteins or
alkaloids, reaction with phenolic rings, and depolymerisation. (Augustine 1992)
Goldbeater's skin test
When goldbeater's skin or ox skin is dipped in HCl, rinsed in water, soaked in the tannin
solution for 5 minutes, washed in water, and then treated with 1% FeSO4 solution, it gives a
blue black colour if tannin was present.
Ferric chloride (FeCl3) test
It is rather a test for phenolics in general. Powdered plant leaves of the test plant (1.0 g) are
weighed into a beaker and 10 ml of distilled water are added. The mixture is boiled for five
minutes. Two drops of 5% FeCl3 are then added. Production of a greenish precipitate was an
indication of the presence of tannins. Alternatively, a portion of the water extract is diluted
with distilled water in a ratio of 1:4 and few drops of 10% ferric chloride solution is added. A
blue or green colour indicates the presence of tannins (Evans, 1989).
Other methods
The hide-powder method is used in tannin analysis for leather tannin and the Stiasny method
for wood adhesives. Statistical analysis reveals that there is no significant relationship
between the results from the hide-powder and the Stiasny methods.
Hide-powder method
400 mg of sample tannins are dissolved in 100 ml of distilled water. 3 g of slightly chromated
hide-powder previously dried in vacuum for 24h over CaCl2 are added and the mixture stirred
for 1 h at ambient temperature. The suspension is filtered without vacuum through a sintered
glass filter. The weight gain of the hide-powder expressed as a percentage of the weight of
the starting material is equated to the percentage of tannin in the sample.
Stiasny's method
100 mg of sample tannins are dissolved in 10 ml distilled water. 1 ml of 10M HCl and 2 ml
of 37% formaldehyde are added and the mixture heated under reflux for 30 min. The reaction
mixture is filtered while hot through a sintered glass filter. The precipitate is washed with hot
43
water (5x 10 ml) and dried over CaCl2. The yield of tannin is expressed as a percentage of the
weight of the starting material
References
1 Römpp, Lexikon der Chemie, CD-version, Thieme, Stuttgart, 1997.
2 H. Ottiger and U. Reeb, Gerben, Eugen Ulmer GmbH, Stuttgart, Germany, 1991.
3 E. Haslam, Plant Polyphenols – Vegetable Tannins Revisited – Chemistry and
Pharmacology of Natural Products, Cambridge University Press, Cambridge, 1989, p. 165.
4 L. J. Porter, in Methods in Plant Biochemistry-Plant Phenolics, Series ed P. M. Dey and J.
B. Harborne, Academic Press, London, 1989, vol. 1, p. 389.
5 J. Falbe and M. Regitz, CD RÖMPP Chemie Lexikon, Version 1.0, Georg Thieme Verlag,
Stuttgart/New York, 1995.
6 T. Yoshida, H. Ohbayashi, K. Ishihara, W. Ohwashi, K. Haba, Y. Okano, T. Shingu and T.
Okuda, Chem. Pharm. Bull., 1991, 39, 2233.
7 T. Okuda, T. Hatano and K. Yazaki, Chem. Pharm. Bull., 1983, 31,
333.
44
8 T. Hatano, K. Yazaki, A. Okonogi and T. Okuda, Chem. Pharm. Bull., 1991, 39, 1689. 9 R.
Saijo, G.-I. Nonaka and I. Nishioka, Chem. Pharm. Bull., 1989, 37, 2063.
10 E. Haslam, J. Nat. Prod., 1996, 59, 205.
11 G. Würdig and R. Woller, Chemie des Weines, Eugen Ulmer GmbH, Stuttgart, 1989.
12 L. Xie, J.-X. Xie, Y. Kashiwada, L. M. Cosentino, S.-H. Liu, R. B. Pai, Y.-C. Cheng and
K.-H. Lee, J. Med. Chem., 1995, 38, 3003.
13 T. Tanaka, H. Fujisaki, G.-I. Nonaka and I. Nishioka, Chem. Pharm. Bull., 1992, 40,
2937.
14 G.-I. Nonaka, T. Sakai, T. Tanaka, K. Mihashi and I. Nishioka, Chem. Pharm. Bull., 1990,
38, 2151.
15 T. Tanaka, H.-H. Tong, Y.-M. Xu, K. Ishimaru, G.-I. Nonaka and I. Nishioka, Chem.
Pharm. Bull., 1992, 40, 2975.
16 T. Hatano, N. Ogawa, T. Yasuhara and T. Okuda, Chem. Pharm. Bull., 1990, 38, 3308.
17 J.-H. Lin, G.-I. Nonaka and I. Nishioka, Chem. Pharm. Bull., 1990, 38, 1218.
18 T. Yoshida, T. Chou, A. Nitta, K.-I. Miyamoto, R. Koshiura and T. Okuda, Chem. Pharm.
Bull., 1990, 38, 1211.
19 M. Nishizawa and T. Yamagishi, J. Chem. Soc., Perkin Trans. 1, 1982, 2963.
20 E. A. Haddock, R. K. Gupta and E. Haslam, J. Chem. Soc., Perkin Trans. 1, 1982, 2535.
21 Y. Kashiwada, L. Huang, R. E. Kilkuskie, A. J. Bodner and K.-H. Lee, Bioorg. Med.
Chem. Lett., 1992, 2, 235.
22 E. A. Haddock, R. K. Gupta, S. M. K. Al-Shafi and E. Haslam, J. Chem. Soc., Perkin
Trans. 1, 1982, 2515.
23 T. Hatano, A. Okonogi, K. Yazaki and T. Okuda, Chem. Pharm. Bull., 1990, 38, 2707.
24 T. Tanaka, G.-I. Nonaka and I. Nishioka, Chem. Pharm. Bull., 1986, 34, 650.
25 T. Kadota, Y. Takamori, K. Nyein, T. Kikuchi, K. Tanaka and H. Ekimoto, Chem. Pharm.
Bull., 1990, 38, 2687.
26 T. Yoshida, T. Chou, Y. Maruyama and T. Okuda, Chem. Pharm. Bull., 1990, 38, 2681.
27 T. Tanaka, G.-I. Nonaka and I. Nishioka, Chem. Pharm. Bull., 1990, 38, 2424.
28 T. Tanaka, G.-I. Nonaka and I. Nishioka, Chem. Pharm. Bull., 1986, 34, 656.
29 T. Okuda, T. Yoshida, M. Ashida and K. Yazaki, J. Chem. Soc., Perkin Trans. 1, 1983,
1765.
30 T. Yoshida, W. Ohwashi, K. Haba, H. Ohbayashi, K. Ishihara, Y. Okano, T. Shingu and
T. Okuda, Chem. Pharm. Bull., 1991, 39, 2264.
45
31 T. Yoshida, K. Haba, F. Nakata, Y. Okano, T. Shingu and T. Okuda, Chem. Pharm. Bull.,
1992, 40, 66. 32 T. Yoshida, O. Namba, C.-F. Lu, L.-L. Yang, K.-Y. Yew and T. Okuda,
Chem. Pharm. Bull., 1992, 40, 338.
33 T. Yoshida, K. Haba, R. Arata, F. Nakata, T. Shingu and T. Okuda, Chem. Pharm. Bull.,
1995, 43, 1101.
34 S. El-Mekkawy, M. R. Meselhy, I. T. Kusumoto and S. Kadota, Chem. Pharm. Bull.,
1995, 43, 641.
35 T. Hatano, L. Han, S. Taniguchi, T. Okuda, Y. Kiso, T. Tanaka and T. Yoshida, Chem.
Pharm. Bull., 1995, 43, 2033.
36 T. Yoshida, T. Chou, A. Nitta and T. Okuda, Chem. Pharm. Bull., 1991, 39, 2247.
37 T. Yoshida, Y. Ikeda, H. Ohbayashi, K. Ishihara, W. Ohwashi, T. Shingu and T. Okuda,
Chem. Pharm. Bull., 1986, 34, 2676.
38 T. Yoshida, T. Chou, K. Haba, Y. Okano, T. Shingu, K.-I. Miyamoto and R. K. T. Okuda,
Chem. Pharm. Bull., 1989, 37, 3174.
39 T. Yoshida, T. Hatano, T. Kuwajima and T. Okuda, Heterocycles, 1992, 33, 463.
40 Y.-J. Tsai, T. Aoki, H. Maruta, H. Abe, H. Sakagami, T. Hatano, T. Oku
41 T. Okuda, T. Yoshida, T. Hatano, T. Koga, N. Toh and K. Kariyama, Tetrahedron Lett.,
1982, 23, 3941.
42 L. Han, T. Hatano, T. Okuda and T. Yoshida, Chem. Pharm. Bull., 1995, 43, 2109.
43 L.-G. Chen, L.-L. Yang, K.-Y. Yen, T. Hatano, T. Yoshida and T. Okuda, Chem. Pharm.
Bull., 1995, 43, 2088.
44 T. Okuda, T. Hatano, K. Yazaki and N. Ogawa, Chem. Pharm. Bull., 1982, 30, 4230.
45 T. Okuda, T. Hatano and N. Ogawa, Chem. Pharm. Bull., 1982, 30, 4234.
46 S. Morimoto, G.-I. Nonaka and I. Nishioka, Chem. Pharm. Bull., 1986, 34, 643.
47 S. Morimoto, G.-I. Nonaka and I. Nishioka, Chem. Pharm. Bull., 1986, 34, 633.
48 T. Hatano, N. Ogawa, R. Kira, T. Yasuhara and T. Okuda, Chem. Pharm. Bull., 1989, 37,
2083.
49 G.-I. Nonaka, K. Ishimaru, R. Azuma, M. Ishimatsu and I. Nishioka, Chem. Pharm. Bull.,
1989, 37, 2071.
50 M. Nishizawa and T. Yamagishi, J. Chem. Soc., Perkin Trans. 1, 1983, 961.
51 G.-I. Nonaka, S. Nakayama and I. Nishioka, Chem. Pharm. Bull., 1989, 37, 2030.
52 T. Yoshida, T. Hatano, T. Okuda, M. U. Memon, T. Shingu and K. Inoue, Chem. Pharm.
Bull., 1984, 32, 1790.
46
53 T. Okuda, T. Yoshida, T. Hatano, K. Yazaki and M. Shida, Phytochemistry, 1982, 21,
2871.
54 T. Hatano, O. Namba, L. Chen, T. Yasuhara, K. Yazaki, T. Yoshida and T. Okuda,
Heterocycles, 1990, 31, 1221.
55 R. Saijo, G.-I. Nonaka and I. Nishioka, Chem. Pharm. Bull., 1989, 37, 2063.
56 T. Okuda, T. Yoshida, T. Hatano, T. Koga, N. Toh and K. Kuriyama, Tetrahedron Lett.,
1982, 23, 3937.
57 T. Okuda, T. Yoshida and T. Hatano, J. Chem. Soc., Perkin Trans. 1, 1982, 9.
58 M. Ishimatsu, T. Tanaka, G. Nonaka, I. Nishioka, M. Nishizawa and T. Yamagishi, Chem.
Pharm. Bull., 1989, 37, 1735.
59 T. Tanaka, S. Kirihara, G.-I. Nonaka and I. Nishioka, Chem. Pharm. Bull., 1993, 41, 1708.
60 J.-D. Su, T. Osawa, S. Kawakishi and M. Namiki, Phytochemistry, 1988, 27, 1315.
61 T. Tanaka, G.-I. Nonaka and I. Nishioka, J. Chem. Soc., Perkin Trans. 1, 1986, 369.
62 D. J. Zeeb, B. C. Nelson, K. Albert and J. J. Dalluge, Anal. Chem., 2000, 72, 5020.
63 R. Niemetz, G. Schilling and G. G. Gross, Chem. Commun., 2001, 35.
64 P. Luger, M. Weber, S. Kashino, Y. Amakura, T. Yoshida, T. Okuda, G. Beurskens and Z.
Dauter, Acta Crystallogr., 1998, B54, 687.
65 H. Ito, T. Hatano, O. Namba, T. Shirono, T. Okuda and T. Yoshida, Chem. Pharm. Bull.,
1999, 47, 1148.
66 T. Yoshida, F. Nakata and T. Okuda, Chem. Pharm. Bull., 1999, 47, 824.
67 Y. Amakura, M. Miake, H. Ito, S. Murakaku, S. Araki, Y. Itoh, C.-F. Lu, L.-L. Yang, K.-
Y. Yen, T. Okuda and T. Yoshida, Phytochemistry, 1999, 50, 667.
68 H. Ito, K. Miki and T. Yoshida, Chem. Pharm. Bull., 1999, 47, 536.
69 J. H. Izasa, H. Ito and T. Yoshida, Heterocycles, 2001, 55, 29.
70 T. Yoshida, Y. Amakura, N. Yokura, H. Ito, J. H. Izasa, S. Ramirez, D. Pelaez and S. S.
Renner, Phytochemistry, 1999, 52, 1661.
71 T. Hatano, Y. Shintani, Y. Aga, S. Shiota, T. Tsuchiya and T. Yoshida, Chem. Pharm.
Bull., 2000, 48, 1286.
72 J. Conrad, B. Vogler, S. Reeb, I. Klaiber, S. Papajewski, G. Roos, E. Vasquez, M. C.
Setzer and W. Kraus, J. Nat. Prod., 2001, 64, 294.
73 S. Shiota, M. Shimizu, T. Mizusima, H. Ito, T. Hatano, T. Yoshida and T. Tsuchiya,
FEMS Microbiol. Lett., 2000, 185, 135.
74 S. Quideau and K. S. Feldman, Chem. Rev., 1996, 96, 475.
47
75 N. Kakiuchi, M. Hattori, M. Nishizawa, T. Yamagishi, T. Okuda and T. Namba, Chem.
Pharm. Bull., 1986, 34, 720.
76 K. Miyamoto, N. Kishi, R. Koshiura, T. Yoshida, T. Hatano and T. Okuda, Chem. Pharm.
Bull., 1987, 35, 814.
77 Y. Kashiwada, G.-I. Nonaka, I. Nishioka, L. M. Ballas, J. B. Jiang, W. P. Janzen and K.
H. Lee, Bioorg. Med. Chem. Lett., 1992, 2, 239.
78 Y. Kashiwada, G.-I. Nonaka, I. Nishioka, J.-J. Chang and K.-H. Lee, J. Nat. Prod., 1992,
55, 1033.
79 Y. Kashiwada, G.-I. Nonaka, I. Nishioka, K. Jiann-Hung Lee, I. Bori, Y. Fukushima, K. F.
Bastow and K.-H. Lee, J. Pharm. Sci., 1993, 82, 487.
80 J. Jankun, S. H. Selman and R. Swiercz, Nature, 1997, 387, 561.
81 M. Rouhi, Chem. Eng. News, 1997, 9, 11.
82 A. J. Vlietinck, T. De Bruyne, S. Apers and L. A. Pieters, Planta Med., 1998, 64, 97.
83 P. Grunwald, Nachr. Chem. Tech. Lab., 1998, 46, 853.
84 E. Haslam, Plant Polyphenols – Vegetable Tannins Revisited – Chemistry and
Pharmacology of Natural Products, Cambridge University Press, Cambridge, 1989, p. 9.
85 D. W. Griffiths, in Toxic Substances in Crop Plants, ed. J. P. F. D’Mello, D. M. Duffus
and J. H. Duffus, The Royal Society of Chemistry, Cambridge, 1991, p. 180.
86 (a) E. Haslam and Y. Cai, Nat. Prod. Rep., 1994, 11, 41; (b) D. Ferreira, R. J. J. Nel and
R. Bekker, Comprehensive Natural Product Chemistry, ed. B. M. Pinto and S. Fraser,
Elsevier, Amsterdam, 1999, vol. 3, p. 747; (c) G. G. Gross, Comprehensive Natural Product
Chemistry, ed. B. M. Pinto and S. Fraser, Elsevier, Amsterdam, 1999, vol. 3, p. 799.
87 H. Beyer and W. Walter, Lehrbuch der Organischen Chemie, ed. S. Hirzel, Verlag,
Stuttgart, 21st edn., 1988, 553.
88 K. Weinges and P. Plieninger, Eur. J. Org. Chem., 1999, 707.
89 G.-I. Nonaka, H. Nishimura and I. Nishioka, J. Chem. Soc., Perkin Trans. 1, 1985, 163.
90 H. Nishimura, G.-I. Nonaka and I. Nishioka, Phytochemistry, 1986, 25, 2599.
91 D. Ferreira and R. Bekker, Nat. Prod. Rep., 1996, 13, 411.
92 Y. Kashiwada, G.-I. Nonaka and I. Nishioka, Phytochemistry, 1988, 27, 1469.
93 K. Ishimaru, G.-I. Nonaka and I. Nishioka, Phytochemistry, 1987,
26, 1501. 94 H. Nishimura, G.-I. Nonaka and I. Nishioka, Chem. Pharm. Bull., 1984, 32,
1741.
95 A. Itoh, T. Tanahashi, S. Ikejima, M. Inoue, N. Nagakura, K. Inoue, H. Kuwajima and H.
X. Wu, J. Nat. Prod., 2000, 63, 95.
48
96 K. Bock, N. F. LaCour, S. R. Jensen and B. J. Nielsen, Phytochemistry, 1980, 19, 2033.
97 Y. Kashiwada, G.-I. Nonaka and I. Nishioka, Chem. Pharm. Bull., 1984, 32, 3461.
98 R. Saijo, G. Nonaka and I. Nishioka, Phytochemistry, 1989, 28, 2443.
99 G.-I. Nonaka and I. Nishioka, Chem. Pharm. Bull., 1983, 31, 1652.
100 G.-I. Nonaka, H. Nishimura and I. Nishioka, Chem. Pharm. Bull., 1982, 30, 2061.
101 T. Tanaka, T. Sueyasu, G.-I. Nonaka and I. Nishioka, Chem. Pharm. Bull., 1984, 32,
2676. 102 Y. Kashiwada, G.-I. Nonaka, I. Nishioka and T. Yamagishi, Phytochemistry, 1988,
27, 1473.
103 R. Saijo, G.-I. Nonaka and I. Nishioka, Phytochemistry, 1989, 28, 2443.
104 G. Krow, Top. Stereochem., 1970, 5, 59.
105 R. S. Cahn, C. Ingold and V. Prelog, Angew. Chem., 1966, 78, 413.
106 M. Öki, Top. Stereochem., 1983, 14, 1.
107 G. G. Gross, Acta Hortic., 1994, 381, 74.
108 H. Rausch and G. G. Gross, Z. Naturforsch., C: Biosci., 1996, 51, 473.
109 S. Hagenah and G. G. Gross, Phytochemistry, 1993, 32, 637.
110 A. S. Hofmann and G. G. Gross, Arch. Biochem. Biophys., 1990, 283, 530.
111 M. Ishimatsu, T. Tanaka, G. Nonaka, I. Nishioka, M. Nishizawa and T. Yamagishi,
Chem. Pharm. Bull., 1989, 37, 129.
112 G. Nonaka, M. Ishimatsu, T. Tanaka, I. Nishioka, M. Nishizawa and T. Yamagishi,
Chem. Pharm. Bull., 1987, 35, 3127.
113 M. Nishizawa, T. Yamagishi, G. Nonaka, I. Nishioka and H. Bando, Chem. Pharm.
Bull., 1982, 30, 1094.
114 K. S. Feldman and A. Sambandam, J. Org. Chem., 1995, 60, 8171.
115 K. S. Feldman and S. M. Ensel, J. Am. Chem. Soc., 1994, 116, 3357.
116 W. Mayer, A. Görner and K. Andrä, Justus Liebigs Ann. Chem., 1977, 1976.
117 T. Tanaka, G.-I. Nonaka and I. Nishioka, Chem. Pharm. Bull., 1986, 34, 1039.
118 K. Miyamoto, T. Murayama, M. Nomura, T. Hatano, T. Yoshida, T. Furukawa, R.
Koshiura and T. Okuda, Anticancer Res., 1993, 13, 37.
119 A. Yanagida, T. Kanda, T. Shoji, M. Ohnishi-Kameyama and T. Nagata, J. Chromatogr.
A, 1999, 855, 181.
120 D. Ferreira and X.-C. Li, Nat. Prod. Rep., 2000, 17, 193.
121 K. Khanbabaee and T. van Ree, Synthesis, 2001, 1585.
49