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A Comprehensive Review on the Genus Leea (Family Leeaceae) with Special Emphasis on the Indian Species

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Nehru et al., IJPSR, 2021; Vol. 12(5): 2559-2569. E-ISSN: 0975-8232; P-ISSN: 2320-5148
International Journal of Pharmaceutical Sciences and Research 2559
IJPSR (2021), Volume 12, Issue 5 (Review Article)
Received on 01 May 2020; received in revised form, 08 October 2020; accepted, 12 April 2021; published 01 May 2021
A COMPREHENSIVE REVIEW ON THE GENUS LEEA (FAMILY LEEACEAE) WITH
SPECIAL EMPHASIS ON THE INDIAN SPECIES
Amisha Nehru, Yash Shah, Jyoti Sharma, Yagni Shah, Parth Thummar, Preeti Verma and Mamta Shah *
Department of Pharmacognosy and Phytochemistry, L. M. College of Pharmacy, Ahmedabad - 380009,
Gujarat, India.
ABSTRACT: The genus Leea distributed majorly in tropical and subtropical
regions of Asia, Africa, and Madagascar, belongs to the family Leeaceae. It
comprises 36 species that are used worldwide for different medicinal
purposes. In this decade, research interests in the genus Leea have grown in
the fields of systematics, phylogenetic studies, analytical chemistry,
identification and isolation of active metabolites, pharmacology, and
phytochemistry. A wide range of phytochemicals with a variety of
pharmacological activities were found to be possessed by different species of
the Leea family, flavonoids, phenolics, triterpenoids, and tannins being the
major ones. Different plant parts are claimed to be used for the treatment of
human and animal ailments. Unlike members of Vitaceae, Leeaceae
members (Leea species) do not form tendrils and include erect herbs, shrubs
and trees but have shared features such as raphides, minute droplets of plant
sap called pearl glands, phloem plastids, common corolla-stamen primordia,
as well as similar wood and testa anatomy similar to Vitaceae family. This
review reveals new insights on the genus Leea and the potential use of
species in the genus as medicinal plants, with Leea indica and Leea
macrophylla being the most important species, whose roots, leaves, and
whole plants possess various pharmacological actions as they are rich in
flavonoids, triterpenoids, and tannins.
INTRODUCTION: It is evident from human
history that plants are of great importance in
traditional as well as modern medicines. Plants
naturally produce secondary metabolites, also
called phytochemicals or biologically active
compounds, which are involved in plant physio-
logy, its protection mechanism, or just act as waste
products for the plants, but might be of great
importance to human beings.
QUICK RESPONSE CODE
DOI:
10.13040/IJPSR.0975-8232.12(5).2559-69
This article can be accessed online on
www.ijpsr.com
DOI link: http://dx.doi.org/10.13040/IJPSR.0975-8232.12(5).2559-69
These bioactive compounds can be used as
precursors for the development of natural, environ-
ment friendly, and low toxicity pharmaceuticals,
nutraceuticals, flavours, fragrances, cosmetics, and
pesticides due to their therapeutic and aromatic
properties 1. Leea is a genus of plants that are
distributed throughout Northern and Eastern
Australia, New Guinea, South, and South-east Asia,
and parts of Africa.
Leea contains approximately 36 species and is
placed in its monogeneric family Leeaceae 1. Out
of the 36 species, India has 11 species distributed in
different states, as mentioned in the database of the
Botanical Survey of India 2, 3. Various studies of
different species of this genus recorded varied
pharmacological actions like antimicrobial, anti-
Keywords:
Leea genus, Leeaceae, Taxonomic
ambiguity, Phytochemistry, Medicinal
uses
Correspondence to Author:
Prof. Mamta B. Shah
Professor & Head,
Department of Pharmacognosy and
Phytochemistry, L. M. College of
Pharmacy, Ahmedabad - 380009,
Gujarat, India.
E-mail: mbshah2007@rediffmail.com
Nehru et al., IJPSR, 2021; Vol. 12(5): 2559-2569. E-ISSN: 0975-8232; P-ISSN: 2320-5148
International Journal of Pharmaceutical Sciences and Research 2560
oxidant, anticancer and nephroprotective effects.
Root and leaf of Leea macrophylla contain
vitamins like thiamine, riboflavin and ascorbic acid
along with vitamin B12 4. The main active consti-
tuents found in different species are flavonoids,
triterpenoids, tannins, phenolic acids, and phthalate
esters 3, 4. This review presents comprehensive
information on Leea genus, including habit,
distribution, pharmacognosy, phytochemistry,
traditional uses, and pharmacological properties of
plants of different species under the genus. In the
review, an attempt has also been made to ponder
over the significance of controversy revolving
around the preferred family for the genus Leea.
MATERIALS AND METHODS: A thorough
literature survey of the genus Leea with focus on
Indian species was carried out, and information was
gathered using scientific publications and
conference proceedings from Science Direct,
PubMed, Google Scholar, Web of Science, Scopus,
Springer Links, and ACS Publications, Scifinder,
Books, Journals, etc. Besides, bibliographies of
referred articles on the pharmacognostic, phyto-
chemical, pharmacological and medicinal aspects
of various species of Leea were also referred.
Taxonomic Ambiguity: Leeaceae, earlier
excluded from the family Vitaceae, is monogeneric
with about 36 species, of which 11 occur in India 5.
Members of this family are primarily confined to
Malaysia, Indo-china extending to Micronesia and
Melanesia, tropical and subtropical Asia, Australia,
and tropical Africa. The tropical plant genus Leea,
named after the 18th-century English nurseryman
James Lee, is the closest relative to the botanical
family of the grapes, Vitaceae.
It was originally described by Van Royen, but was
formally published by Linnaeus in 1767, with Leea
aequata designated as the type species. Leea genus
was formerly placed in Sapotaceae and was thought
to be related to either Meliaceae or Sterculiaceae. It
was also more recently associated with Rhamnales
until this was refuted by molecular evidence 6-8. In
contrast, according to some taxonomists, Leea was
originally assigned to the family Ampelideae but
was transferred to the Leeaceae and then again to
Vitaceae 9-14. The Angiosperm Phylogeny Group
(APG) considers Leea as a member of Vitaceae,
under the subfamily Leeioideae Burmeister, with
the rest of the 14 genera in subfamily Viticoideae
Eaton. of the order Vitales, due to shared features
such as raphides, pearl glands, phloem plastids,
common corolla-stamen primordia as well as
similar wood and testa anatomy 12, 13, 15, 16.
However, unlike members of Vitaceae, plants-
species under Leea genus do not form tendrils and
include erect herbs, shrubs, and trees (not climbing
vines) with terminal inflorescence and
characteristically large stipules that protect the
developing leaves. Leea flowers also possess
ovaries with secondary septa and a distinct
elaborate floral tube capped by stamens fused at the
center 11, 15, 16.
The stamens detach as a coherent unit sometimes
during anthesis to reveal the receptive stigma 8, 17.
The APG IV system places Leea in the subfamily
Leeoideae (Vitaceae) 18. It is occasionally tagged in
its own monogeneric family, Leeaceae based on
morphological differences between it and Vitaceae
10, 11, 15, 16. These differences include ovule number
per locule (two in Vitaceae and one in Leeaceae),
carpel number (two in Vitaceae and three in
Leeaceae), and the absence or presence of a
staminoidal tube (present in Leeaceae) and floral
disc (present in Vitaceae).
Pollen structure has also been examined for
taxonomic demarcation, though studies have
concluded that the pollen of Leeaceae is unique
compared to Vitaceae, suggesting the families
should remain separate 11, 17. Researchers noted the
presence of trihydroxy compounds in Leea, a
phytochemical trait lacking in the grapes. On the
basis of these morphological differences and
phytochemical differences, it has been preferred by
the researchers to continue segregation of Leea into
its own family, Leeaceae, as originally described
earlier 19.
Habit and Distribution: Leea species grow in dry
deciduous forests, open grasslands, and montane or
lowland rainforests throughout the Old World
tropics from Africa to Asia, North-east Australia,
New Guinea, and Islands of the Pacific, but are
most diverse in Indo-malaya, including India, Indo-
china (including Cambodia, Laos, Myanmar,
Thailand, and Vietnam), tropical China and
Malaysia (including Brunei, Indonesia, East Timor,
New Guinea, Philippines, and Singapore) 20. In
Nehru et al., IJPSR, 2021; Vol. 12(5): 2559-2569. E-ISSN: 0975-8232; P-ISSN: 2320-5148
International Journal of Pharmaceutical Sciences and Research 2561
India, it has a brief distribution of various species
found in the Indian subcontinent:
Leea aequata L. in Uttar Pradesh, Bihar, West
Bengal, Sikkim, Assam, Arunachal Pradesh,
Odisha, Madhya Pradesh, Maharashtra,
Karnataka, Tamil Nadu and Andaman islands
3, 9.
Leea alata Edgew in Gangetic plains, Eastern
and Central India, ascending up to 1500 m in
the Himalaya, Himachal Pradesh, Uttar
Pradesh, Bihar, West Bengal, Sikkim, Assam,
Arunachal Pradesh, Meghalaya, Odisha, and
Madhya Pradesh 3, 9.
Leea angulata Korth. Ex Miq. in the coastal
belts and Nicobar islands 9.
Leea asiatica (L.) in Ridsdale in evergreen,
deciduous and lower mountain forests, up to
2250 m in the Himalaya, Uttar Pradesh, in
grasslands and the plains of Jammu and
Kashmir, Himachal Pradesh, Madhya Pradesh,
Bihar, West Bengal, Sikkim, Tamil Nadu,
Kerala, Arunachal Pradesh, Assam, Odisha,
Nagaland, Manipur, Mizoram, Andhra
Pradesh, Meghalaya, Rajasthan, Bihar, Deccan
(Sandur hills), Maharashtra, Karnataka and
Andaman islands 3, 9, 20.
Leea compactiflora Kurz. in evergreen forests
up to 2000 m in Uttar Pradesh (Terai), West
Bengal, Sikkim, Arunachal Pradesh, Nagaland,
Assam, Manipur, Mizoram and Meghalaya 9, 21.
Leea grandifolia Kurz. in the coastal areas,
Andaman and Nicobar islands 9.
Leea guineensis G. Don in Uttar Pradesh,
Sikkim, Assam, Manipur, Tamil Nadu,
Meghalaya, Maharashtra, and the Andaman
islands 22-23.
Leea indica (Burm. f.) Merr. in Punjab, Uttar
Pradesh, Bihar, West Bengal, Sikkim,
Arunachal Pradesh, Assam, Goa, Nagaland,
Mizoram, Tripura, Madhya Pradesh,
Meghalaya, Odisha, Maharashtra, Andhra
Pradesh, Tamil Nadu, Kerala, and Andaman
and Nicobar islands 20-23.
Leea macrophylla Roxb. ex Hornem. in Sub-
Himalayan tract up to 2250 m and the Western
Ghats, Uttar Pradesh, Bihar, West Bengal,
Sikkim, Assam, Meghalaya, Odisha, Madhya
Pradesh, Maharashtra, Andhra Pradesh,
Karnataka, Tamil Nadu, Kerala, and Andaman
island 20-23.
Leea rubra Blume ex Spreng. in West Bengal,
Assam and Meghalaya 21, 22.
Leea setuligera Clarke in Assam, Maharashtra
(Khandala) and Karnataka (Konkan) 9, 22.
Pharmacognostical Features: The distinguishing
morphological features of some commonly
occurring Indian species of genus Leea are
mentioned in Table 1.
Phytochemistry: The major classes that have been
studied in different species of Leea are flavonoids,
triterpenoids, and phenolic acids. Leea indica
[Local names- Bandicoot berry (English),
Kurkurjihwa (Hindi)] 24. It is one of the most
important species of genus Leea in India, and
different parts are reported to show the presence of
23 known chemical compounds, including 11
hydrocarbons, phthalic acid, palmitic acid, 1-
eicosanol, solanesol, farnesol, three phthalic acid
esters, gallic acid, quercetin, lupeol, β-sitosterol
and ursolic acid 26-29. L. macrophylla [Local names-
Hastikarnapalasha, Hathikana (Hindi), Dholsa-
mudrika, Samudraka (Sanskrit)] 30. The leaf is
documented to contain abundant phenolic
constituents such as flavonoids, leucoantho-
cyanidins, p-hydroxybenzoic acid, syringic acid
and gallic acid 25.
Oleanolic acid, oleanolic acid derivative 7α, 28-
olean diol and stigmasterol have been isolated by
chromatograpy from the ethanolic extract of the
root 31. Root and leaf are reported to contain
appreciable amounts of vitamin B1 (thiamine),
vitamin B2 (riboflavin), vitamin C (ascorbic acid)
and vitamin B12 4. Chlorogenic acid, a phenolic
acid, is noted to be present in root 32. Compounds
identified in the ethanol extract of root by GC-MS
are 2,2-Bis (chloromethyl)-1-propanol; 2H Pyran
2 - one; tetrahydro-4-hydroxy-6-pentyl; butylated
hydroxytoluene; benzaldehyde; 3-ethoxy-
tetradecanoic acid; pentadecanoic acid; n-
hexadecanoic acid; l-(+)-ascorbic acid; 2,6-
dihexadecanoate; 9-octadecenoic acid; 1,2,3-
propanetriyl ester; octadecanoic acid; 12,13-epoxy-
octadec-9-enoic acid; eicosanoic acid; docosanal;
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International Journal of Pharmaceutical Sciences and Research 2562
(2,3-diphenylcyclopropyl)methylphenyl sulfoxide;
2 Hydroxy 4 methoxy - 7 - methyl 7, 8, 9, 10,
11, 12, 13, 14 octahydro 6 oxabenzo-
cyclododecen 5 - one; bis (2-ethylhexyl)
phthalate; (2,3-diphenylcyclopropyl)methylphenyl
sulfoxide, (2,3-diphenylcyclopropyl)methylphenyl
sulfoxide; 7-methoxy-3-(3,4-dimethoxyphenyl)-4H
chromen 4 - one; tetrapentacontane; 1,54-
dibromo - 2, 2 dimethyl 6 - methylene-1-(3,5-
dihydroxy 1 - pentenyl) cyclohexan - 1-
perhydrol; stigmasta-4,7,22-trien--ol; cholesta-
4,6-dien-3-ol; (3β) - stigmasterol; γ - sitosterol;
ergosta-4,6,8, 22-tetraen-3-one; 4,22-cholestadien-
3-one; cyclopropa-33-norgorgostan-3-ol, 3',6-
dihydro-(3β,5β,6α,22.xi.,23.xi.); γ-sitostenone and
cholesterol epoxide. The major components noted
amongst these are n-hexadecanoic acid (37.15%),
9-octadecenoic acid, 1, 2, 3-propanetriyl ester
(18.87%), octadecanoic acid (12.56%), γ-
sitostenone(5.88%) and γ-sitosterol (4.13%) 33.
TABLE 1: DISTINGUISHING MORPHOLOGICAL FEATURES OF COMMON INDIAN SPECIES OF GENUS LEEA
L. aequata 10, 11, 21
L. compactiflora 22
L. indica 24, 25
L. macrophylla 25
L. rubra 23
Large shrubs,
young branches
villous
Undershrubs, up to
3 m tall, branches
often ribbed
Erect shrub or
small tree, 2-10 m
tall, with aerial
roots
Herbaceous shrub or
small tree, 2m tall
semi-woody shrub
up to 3 m tall
Leaves:
Type: Compound,
Alternate,
Pinnate, stipulate
Shape: Oblong-
obovate, leaflets
oblong-lanceolate,
cuneate to truncate
Apex: Acuminate
to caudate
Base: Subcordate
or rounded,
petiolate
Margin: Sharply
serrate
Surface: Pubescent
to densely hairy,
caduceus,
membranous,
hispid with
scattered grey hairs
above, hirsute on
nerves, rough with
scattered rounded
brown peltate
glands beneath
Venation: Lateral
nerves 8-12 pairs,
slender, arched
Leaves:
Type: Compound,
unipinnate, rarely
trifoliate
Shape:
Narrowly winged
Apex:
Acute
Base:
Sessile, unequal
Margin: Dentate-
serrate
Surface: Glabrous
on both sides,
minutely pubescent
on nerves beneath,
chartaceous to
subcoriaceous,
reddish, sparsely
distributed stellate
pearl glands
Venation:
Secondary nerves
8-12 pairs, curved
near the margins
Leaves:
Type:
Compound,
bipinnate to
tripinnate,
alternate, spiral,
stipules purple,
sheathing
Shape:
Obovate-oblong
leaflets ovate to
lanceolate
Apex:
Acuminate to
caudate
Base:
Acute to rounded
Margin: Serrate
to dentate
Surface:
Glabrous,
drying brown
Venation:
Midrib raised
above; secondary
nerves 7-12 pairs;
tertiary nerves
reticulo-
percurrent
Leaves:
Type: Simple
Shape: Broadly
ovate, nearly as
broad as long, lower
leaves 60 cm long,
upper leaves 15-23
cm long
Apex:
Acute or acuminate
Base:
Petioles 5-12 cm
long, deeply striated
Margin: Coarsely
serrate or sub-lobed
Surface: Pubescent
beneath, main
nerves opposite,
very prominent and
8-10 pairs, pearl
glands absent, upper
leaves light
yellowish-green,
lower leaves dark
green
Venation: Lateral
nerves to 14 pairs,
pubescent to hairy
Leaves:
Type: Compound,
2-4 pinnate,
alternate,
petiolate stipules as
a narrow wing,
similarly long
Shape:
Leaflets numerous,
ovate to ovate-
oblong
Apex:
Acute to shortly
acuminate
Base:
Rounded to acute
Margin: Crenate
to shallowly serrate
Surface: Glabrous
or less frequently
with small hairs
along the nerves,
chartaceous, pearl
glands apparently
absent from the
leaflets
Venation:Nerves 5-
10 pairs, sometimes
with minute hairs,
often winged
Inflorescence:
Corymbs, 5-
Merous Flowers:
Greenish white,
calyx lobed
halfway down,
glabrous to densely
pubescent, covered
with pearl glands
outside, lobes
deeply cleft, ovary
4-7 loculed
Inflorescence:
Reddish, glabrous
or minutely
pubescent,
peduncle, 4-20 cm
long bracts and
bracteoles
inconspicuous
Flowers:
Red, calyx
glabrous,
corolla tube with
staminodial lobes,
ovary 6-locular
Inflorescence:
Corymbose
cymes
Flowers:
Calyx green,
petals cream
forked near the
margin, and
spreading
Inflorescence:
Terminal, much-
branched,
puberculous,
corymbose cymes,
up to 30 cm long
Flowers:
Greenish white,
calyx 5-lobed,
pubescent, lobes 3-
angled, linear-ovate,
greyish-pubescent
to papillose
Inflorescence:
Rusty pubescent,
generally compact,
bracts deltoid-
triangular
Flowers:
Pentamerous, bright
red with a yellow
central disc,
glabrous, shallowly
retuse or cleft
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International Journal of Pharmaceutical Sciences and Research 2563
Fruit:
Globose-depressed,
6-7 mm, orange-
red, black when
ripe, seeds 3-6
Flowering and
fruiting: July-
December
Fruit:
Berry, 0.5-1 cm
across, red, bluish
purple when ripe,
seeds 4-6
Flowering: May-
June Fruiting:
August-January
Fruit:
Berry, depressed,
globose, 0.7-1 cm
across, purple
black, seeds 4-6
Flowering and
fruiting:
July-December
Fruit:
Berry globose, 6-8
cm in diameter,
black, 3-6 celled,
depressed globose,
usually 3-6 lobed
Flowering and
fruiting:
November-
December
Fruit:
Sub-globose berries,
8-10 mm, dark red
or purple when ripe;
Seeds 6, 7-10 mm
wide, rumination
outline simple and
endosperm simply
ruminate
Flowering and
fruiting: November-
December
L. guineensis: Quercetin - 3' - sulphate 3 - O - α-
L-rhamnopyranoside, quercetin-3,3'-disulfate and
quercetin-3,3',4'-trisulfate, along with kaempferol,
quercetin, quercitrin, mearnsitrin, gallic acid, and
ethyl gallate have been isolated and identified from
the leaf 34.
L. asiatica: About 24 compounds have been
identified during the phytochemical analysis of L.
asiatica, including a phenolic glucoside, seven
triterpenoids, eight flavonoids, two phenolic
glycosides, four diglycosidic compounds, and two
miscellaneous compounds 35.
Traditional Uses: The whole plant of Leea indica
is used traditionally for the treatment of headaches,
body pains, and skin complaints. The root is valued
in diarrhoea, colic, dysentery, and as a sudorific.
Leaves are consumed for the treatment of cancer,
diabetes, and injuries 36. A leaf is roasted and
applied to the head in vertigo. The juice of young
leaves is useful as a digestive. Inflorescence extract
is used to cure chest pain in children 28, 36.
Leea species including L. asiatica, L. guineensis, L.
indica and L. macrophylla are used to treat skin
lesion and wounds. The leaf of L. macrophylla
possesses anodyne property and is applied to
wounds and sores. It is also used for guinea worm
and ringworm 37. It is also noted to be traditionally
used for tonsillitis, tetanus, nephrolithiasis,
rheumatism, arthritis, snake bites, sore, pain and
blood effusion 38, 39. The plants of L. macrophylla
possess tikta, katu rasa, sangrahi, vikashiguna,
ushnaveerya, madhuravipaka properties and have
Rasayana karma. L. macrophylla bearing either
unifoliate, trifoliate or 1 to 3 pinnate leaves should
be considered as botanical equivalents of classical
Ayurvedic plant Hastikarna or Hastikarnapalasha
40. In Ayurveda, it is indicated in worm infestation,
dermatopathies, wounds, inflammation and in
symptoms of diabetes 41. Dried powder of its root
with clarified butter is prescribed in the morning as
age sustainer 4. The leaves are also used in making
small flute 42. They are also used as platters 25. The
root is said to yield a dye 43. L. macrophylla
contains vitamin C that maintains collagen protein
necessary for the formation of connective tissue in
the skin, ligaments, and bones. It protects thiamine
and riboflavin from oxidation. Thus it plays a vital
role in nutrition point of view 4.L. aequeta finds its
use in itching and dyspraxia 24. Its leaves and twigs
have been used as antiseptic to treat wounds 25.
Ethnic Uses: Ethnopharmacological use of L.
macrophylla is documented for the urinary problem
by local tribes of Bihar. The leaves have been used
in goitre, gastric tumor, lipoma, and tetanus. Some
other tribes use the leaf as vegetables 4. Crude
leaves and powder are traditionally used in cancer,
urolithiasis, wounds, sores, goitre, gastric tumor,
tetanus, and urinary disturbances.
Leaf juice is also used as an anti-inflammatory
agent in boils, arthritis, gout, and rheumatism. It is
also applied externally to allay pain and to stop the
effusion of blood. A leaf is extensively used by the
Ayurvedic physicians in the preparation of seasonal
tonic modaka 44. Also, the dried root powder mixed
with clarified butter is prescribed in the morning as
age sustainer 4, 44. An ethnobotanical survey of this
plant shows some important therapeutic uses in
cancer, dysentery, body ache, and sexual disability
45. Besides, L. macrophylla is a non-woody forest
product used as ethnic food in India 46.
Its leaves are eaten as vegetables, and the roots of
the plant are cooked as vegetables 25, 47, 48. The
fruits are consumed orally in the form of juice and
considered very nutritive 47, 49.
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Pharmacological Properties: Several investiga-
tions carried out by researchers show that many
species of Leea genus possess remarkable
pharmacological activities, including anticancer,
anti-bacterial, thrombolytic, anti-inflammatory,
anti-urolithiatic, antioxidant, anti-hyperglycaemic
and many more as described below 24, 25.
Anticancer Activity: Mollic acid arabinoside
isolated from L. indica is found to trigger induction
of mitochondria-mediated apoptosis in Ca-Ski
human cervical cancer cells 28. L. macrophylla also
showed cytotoxic effects in a study using brine
shrimp lethality bioassay. The lethal concentration
(LC50 values) of the ethanolic extract, as well as
carbon tetrachloride, chloroform and ethyl acetate
soluble fractions of roots, were found to be 2.39,
0.049, 4.53, and 0.09 μg/ml, respectively, which
were comparable to the standard vincristine
sulphate who’s LC50 was 0.34 μg/ml 50.
Anti-diarrheal Activity: The methanolic extract of
leaf of L. indica is shown to possess anti-diarrhoeal
activity in castor oil-induced diarrhoea in mice 51.
Anti-hyperglycaemic Activity: The alcoholic and
hydroalcoholic extracts of L. indica leaf revealed
hypoglycemic activity by significantly reducing
blood glucose level in a study using glucose
tolerance test and alloxan-induced diabetes model
in rats 52.
The methanolic extract of L. macrophylla leaf also
exhibits significant effects in ameliorating the
diabetic markers such as insulin and other diabetic-
related markers, especially LDL, HDL, LDH,
creatinine, uric acid and CK-MB, in fructose-fed
streptozotocin (STZ)-induced type 2 diabetes 44.
In another study, L. macrophylla root extract is
reported to upregulate the mRNA expression for
antioxidative enzymes and to repair the necrosis of
pancreatic β-cell and kidney tissues in fructose-fed
STZ-induced type 2 diabetic rats at the doses of 50,
100, and 200 mg/kg. Conversely, the glucose
tolerance ability, liver glycogen level, serum
insulin, organ weight, and pancreatic morphology
are shown to be improved significantly along with
the diameter of the islet of Langerhans (µm), area
occupied by β-cell/islet of Langerhans (µm2) and a
number of β-cells/islet of Langerhans 33.
Anti-inflammatory Activity: Leaves of L. macro-
phylla and L. guineensis have been used to treat
inflammatory diseases. The methanolic extract of
L. macrophylla leaf is noted to inhibit
prostaglandin PGE2, Interleukin IL-6, and cause
reduction of tumor necrosis factor TNF-α.
Furthermore, oral administration of methanol
extract of leaf of L. macrophylla at the doses of 100
and 200 mg/kg is reported to exhibit significant
dose-dependent inhibition of carrageenan-induced
inflammation and reduction of the granuloma tissue
formation 53. L. guineensis leaf is reported to
possess anti-oedematogenic activity in carrageenan-
induced rat paw oedema assay 54.
The methanolic extract of L. indica roots (at 200
and 400 mg/kg doses) is shown to exert significant
anti-inflammatory activity in dinitrobenzene
sulfonic acid (DNBS)-induced Intestinal Bowel
Disease (IBD) in animal experimental models when
compared with standard sulfasalazine (360 mg/kg)
55.
Antimicrobial Activity: The essential oil obtained
from flowers and the ethanolic extract obtained
from leaf of L. indica showed significant activity
against Gram-positive and Gram-negative bacteria.
It was observed that the extract inhibits Gram-
positive bacteria more as compared to Gram-
negative bacteria as indicated by the lowest
Minimum Inhibitory Concentration (MIC value).
Essential oil of L. indica is also reported to be
effective in inhibiting moulds like Aspergillus niger
and Penicillium spp 27. The ethanolic extract of L.
indica leaf also inhibits the growth of Aspergillus
flavus and Candida albicans 51, 56.
L. macrophylla extract, and its successive fraction
from root tubers have also been shown to have
more pronounced effect in the case of Gram-
positive bacteria as compared with Gram-negative
strains. Crude extract of L. macrophylla leaf has
displayed mild to moderate antimicrobial activity
against Bacillus cereus, Bacillus subtilis, and other
test organisms, including Escherichia coli,
Pseudomonas aeruginosa, Salmonella paratyphi,
Shigella dysenteriae, and Shigella sonnei, along
with strong antifungal activity against
Pityrosporum ovale, Trichophyton spp., Candida
albicans, Cryptococcus neoformans, and
Microsporum spp. The ethyl acetate extract of seed
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International Journal of Pharmaceutical Sciences and Research 2565
is noted to be strongly effective against S. aureus as
compared to n-hexane, chloroform, and methanol
extracts 41. The ethanolic extract of the root is
demonstrated to be highly effective against S.
aureus, S. flexneri, and S. boydii, whereas less
effective against S. typhi and Klebsiella pneumonia.
The depicted MIC values ranged from 0.195 to
3.125 mg/ml 57.
Antinociceptive Activity: L. indica and L.
macrophylla leaves have been assessed for their
analgesic effect. Both plants are reported to exhibit
central and peripheral analgesic effects in mice.
The ethanolic extract of L. indica has been shown
to exert analgesic activity in acetic acid-induced
writhing test and formalin-induced licking test 58.
In acetic acid-induced writhing test, the ethanolic
root extract at the dose of 200 mg/kg reduced the
number of writhes significantly with 62.37% of
inhibition. It has been noted that the methanol
extract of leaf L. macrophylla in the oral dose of
100 and 200 mg/kg exhibits significant central and
peripheral analgesic activity in hot-plate test and
acetic acid-induced writhing test in experimental
mice 50.
Antioxidant Activity: The leaf extracts of Leea
species are reported to possess antioxidant potential
using different assays that measure free radical
scavenging activity, such as 2,2-diphenyl-2-
picrylhydrazyl hydrate (DPPH) radical scavenging
activity, ferric thiocyanate (FTC), superoxide
dismutase (SOD), and lipid peroxidation assay, the
activity is attributed to the presence of secondary
metabolites like gallic acid and quercetin 59. The
methanolic extract of L. indica is shown to exhibit
scavenging activity against DPPH radicals. The
crude ethanol extract, along with hexane, ethyl
acetate, and aqueous fractions of ethanol extract
obtained from the leaf of L. indica have been
demonstrated to display antioxidant activity
through DPPH radical scavenging, superoxide
radical scavenging, and reducing power assays 60.
In-vitro studies of different fractions L.
macrophylla leaf have also shown strong free
radical scavenging ability due to the presence of
phenolics 34, 61, 62. In an experimental study,
administration of the L. macrophylla root to the
STZ-induced diabetes animals has been shown to
upregulate the expression profile of genes
responsible for antioxidant enzymes suggesting the
pancreas protecting effect of the plant that is
mediated through an antioxidant dependent event
44. Quercetin - 3'- sulphate 3 O α L
rhamno-pyranoside, quercetin-3,3'-disulphate, and
a new flavonoid sulphate, quercetin-3,3',4'-
trisulphate, together with kaempferol, quercetin,
quercitrin, mearnsitrin, gallic acid, and ethyl gallate
isolated from the leaf of L. guineensis are recorded
to show antioxidant effect on DPPH free radical
scavenging assay 34.
Antiurolithiatic Activity: Administration of the
ethanolic extract of the whole plant of L.
macrophylla (500 mg/kg orally) to rats for 14 days
is reported to significantly reduce as well as
prevent the growth of kidney stones and improve
the renal impairment in the ethylene glycol-induced
urolithiasis model in rats 37, 57.
Antiviral Activity: The essential oil of L .indica is
shown to exhibit antiviral activity against Herpes
simplex virus. The extract is also reported to be
ineffective against vesicular stomatitis virus 63.
Cardiotonic Activity: It is reported that with the
increasing dose of L. macrophylla aqueous and
alcoholic extracts from 0.1 ml to 0.4 ml, a
significant increase in the force of contraction
(positive inotropic effect) and the heart rate
(positive chronotropic effect) is observed 64.
Enzyme Inhibitory Activity: The plant of L.
indica is shown to possess inhibitory activity
against enzymes such as phosphodiesterase,
pancreatic lipase, and glucosidase. The methanolic
extract of L. indica leaf is also observed to be
effective in inhibiting the activity of lipase by
48.5% against porcine pancreatic lipase 65.
Hepatoprotective Activity: Different extracts of L.
macrophylla are also reported to possess significant
hepatoprotective effect in a study, which
demonstrated that most of the extracts except
methanol extract (200 mg/kg) helps in normalizing
the serum creatine kinase (CK-MB) level in hepatic
damage, but the ethyl acetate extract (200 mg/kg)
and chloroform extract (100 mg/kg) restore the
serum CK-MB level 62. Aqueous extract of L.
guineensis seed is found to protect the liver against
dichlorovos-induced toxicity in rats. The ethanolic
extract of L. indica stem bark has been shown to
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International Journal of Pharmaceutical Sciences and Research 2566
have a protective effect against paracetamol-
induced hepatotoxicity in rats 66.
Hypolipidemic Activity: In an experimental study,
the administration of alcoholic and hydro-alcoholic
extracts of L. indica leaf is shown to significantly
decrease the levels of triglycerides, total
cholesterol, LDL and VLDL and increase HDL in
rats, indicating hypolipidemic activity of the leaf
extract 52.
Nephroprotective Activity: The leaf of L. asiatica
has been proven to afford protection in cisplatin-
induced nephrotoxicity in mice. Among the
methanol, ethyl acetate and petroleum ether
extracts of the L. asiatica leaf that were evaluated
for in vitro and ex vivo antioxidant activities, the
methanol extract is shown to exhibit better
antioxidant effects. The effect is attributed to
higher amounts of phenolics (77.75 ± 0.87 mg
Gallic acid equivalent/g of dry material) and
flavanoids (60.98 ± 0.58 mg Quercetin
Equivalent/g of dry material).
The extended study with fractions of the
methanolic extract obtained using methanol, ethyl
acetate, petroleum ether against cisplatin (20
mg/kg, i.p.)-induced nephrotoxicity has revealed
that pretreatment with methanol extract (150 and
300 mg/kg) and its fractions especially methanol
and ethyl acetate fraction (at 75 and 150 mg/kg,
respectively) significantly reduces blood urea
nitrogen, serum creatinine, uric acid and
malondialdehyde levels along with increased total
protein and albumin levels. Ethyl acetate fraction is
indicated to produce highest nephroprotective
activity, possibly by inhibiting lipid peroxidation
process 67.
Neuroprotective Activity: The methanol extract of
the root of L. macrophylla (100 and 200 mg/kg) is
reported to reduce locomotor activity and increase
the duration of sleeping of animals.
The extract is also shown to reduce the content of
malondialdehyde, nitric oxide, and advanced
oxidation protein product and increase the activities
of superoxide dismutase, catalase, and glutathione
peroxidase in hippo-campus 68.
Thrombolytic Activity: The ethanol extract of L.
indica leaf has been reported to have thrombolytic
activity in an in vitro clot lysis assay, where it
produced 39.3% of clot lysis activity 69. According
to another study, the crude extract of L.
macrophylla is observed to exhibit 20.61% clot
lysis compared to the standard streptokinase
(81.53%) in the anti-atherothrombosis assay 57. The
whole plant extract of L. macrophylla is also shown
to have the highest clot lysis activity (47.47%) as
compared to the extracts of other plants like
Ocimum tenuiflorum, Andrographis paniculata,
Adhatoda vasica and Litsea glutinosa 70.
Wound-healing Activity: In an experimental study
using the incision model, L. macrophylla has
shown complete wound contraction in 20 days with
topical application, whereas 22 days by oral
treatment. This effect has been attributed to
increased collagen synthesis and reduced
inflammation through effects on proinflammatory
cytokines and vascular endothelial growth factor
(VEGF), enhanced cellular proliferation as well as
potential antioxidant and free radical scavenging
effects, probably mediated due to the presence of
polyphenols, mainly chlorogenic acid in the extract
32.
CONCLUSION: The genus Leea consists of many
medicinally important species found to be growing
throughout the world. There is a lack of knowledge
on some species within the genus that provides a
huge opportunity for future research. However, the
scientific exploration of various plant species
among this genus has proven the therapeutic
importance of this genus with a variety of
pharmacological actions that are attributed to a
wide range of phytochemicals occurring in the
species. This review acknowledges a few species
out of the 36 species of Leea genus that are found
around the world with keen stress on important
species found in India.
ACKNOWLEDGEMENT: The authors wish to
thank L. M. College of Pharmacy, Ahmedabad,
Gujarat, for providing necessary facilities and
access to online resources for the literature survey
done to gather comprehensive information for the
review article.
CONFLICTS OF INTEREST: The authors
declare that they have no conflict of interest.
Nehru et al., IJPSR, 2021; Vol. 12(5): 2559-2569. E-ISSN: 0975-8232; P-ISSN: 2320-5148
International Journal of Pharmaceutical Sciences and Research 2567
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The antimicrobial, anti-inflammatory, membrane stabilizing and anti-atherothrombosis activities of crude ethanol extract of leaves of Leea macrophylla Roxb. have been investigated. In antimicrobial assay by disc diffusion method, the extract showed mild to moderate antimicrobial activity with zone of inhibition ranging from 9-12 mm and 16-31 mm for test bacteria and fungi, respectively where the growth of Aspergillus niger, Blastomyces dermatidis, Candida albicans, Pityrosporum ovale, Trichophyton sp. Microsporum sp. and Cryptococcus neoformans were strongly inhibited. The extract produced inhibition of protein denaturation and haemolysis by 47.4% and 57.63% in the in vitro anti-inflammatory and membrane stabilization tests, respectively. On the other hand, the crude extract exhibited 20.61% clot lysis compared to the standard streptokinase (SK) (81.53%) in the anti-atherothrombosis activity studies. Preliminary phytochemical screenings with the crude extract revealed the presence of alkaloids, glycosides, tannins, flavonoids, reducing sugars and gums.
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Leea macrophylla Roxb. ex Hornem., a traditional medicinal plant reported remedies for diseases in rural India. However, proper justification and validation of their traditional practice are lacking. Hence this study was done to explore a comprehensive account of phytochemical profiling and antioxidant activities. The presence of phenols, tannins, alkaloids, saponins and flavonoinds was confirmed through phytochemical screening. After estimation of the phytochemical, we get 104.05 mg of GAE/g of phenol, 94.78 mg of GAE/g of tannins, 21.40 mg/g of alkaloids, 05.50 mg/g of saponins and 117.98 mg of QE/g of flavonoids. Its further analysis takes place through GC-MS, get 14 bioactive compounds, which have more than 1% peak area. They had already reported a good medication value in various remedies. The antioxidant test, through DPPH assay, shows, IC 50 values of L. macrophylla is 51.31 µg/mL and gallic acid (taken as standard) have 39.91 µg/mL. By comparing with gallic acid, it can be concluded that Leea macrophylla also has a good antioxidant activity.
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Recent ethnobotanical survey studies highlight about various economic and pharmacological uses of plant Leea macrophylla (LM) Roxb. Ex Hornem. (family: Vitaceae). The aim of the article is bird's eye view of the plant regarding all reported ethnomedicinal information and research works on LM. Information of ethnomedicinal uses of the plant, until December 2018, from available 13 books on ethnobotany, 8 books related to medicinal plants, and 85 research articles on ethnomedicinal claims and pharmacological studies, uses as an ethnic food and economical uses. Information about its use by different tribes across India, parts used, therapeutic indications comprising external (E) and internal (I) usage of drug, recent pharmacological studies, and uses as ethnic food and economical uses are presented in a systematic manner. Root, leaves, and fruits of LM are used in the treatment of various ailments through 26 E applications and 27 I administrations. Root has maximum applications in 31, leaves in 14, seeds in 3, and stem in 1 disease conditions. 12 pre-clinical studies have been conducted on plant to elucidate its pharmacological response in a given disease condition, which includes antiurolithiatic (whole plant), antimicrobial (leaf, seed, and root tuber), anti-inflammatory (leaf), membrane stabilizing (leaf), antithrombotic (leaf and whole plant), hepatoprotective (leaf), antioxidant (leaf), antinociceptive (root), cytotoxic (root), neuroprotective (root), antidiabetic (leaf), wound healing (root tuber), and cardiotonic (whole plant) activity. LM is used as medicine and ethnic food and also for economical usage implying its therapeutic importance. Reported claims can be further revalidated extensive pharmacological and clinical studies, namely bone fractures, healing cut injury, typhoid, sexual weakness, impotency, and cancer.
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Keywords: Leea macrophylla necrosis pancreatic damage type 2 diabetes catalase Dismutase A B S T R A C T This research investigated the functional food effect of Leea macrophylla (Roxb.) ex Hornem root extract on pancreatic necrosis in Streptozotocin-induced type-2 diabetes. Prior to animal intervention, Leea macrophylla root extract (LMR) was subjected to GC-MS analysis. Across a three-week intervention of fructose-fed albino model with LMR50, LMR100 and LMR200, the fluid & food intake, body weight changes, weekly blood glucose concentrations and oral glucose tolerance (OGT) were recorded. The animals were sacrificed after intervention and serum was analyzed for insulin, ALT, AST, LDH, CK-MB, creatinine, uric acid and lipid profile and liver section was used for glycogen estimation. Changes of pancreas and kidney architecture were evaluated by histopathology. Relative mRNA for superoxide dismutase 1 (SOD1), glutathione peroxidase (GPx) and catalase (CAT) were quantitated using assay kits. Results showed that fluid and food intake, weekly blood glucose level, ALT, AST, LDH, CK-MB level were significantly (p < 0.05) decreased in LMR50 group. Conversely, the glucose tolerance ability, liver glycogen level, serum insulin, organ weight and pancreatic morphology were improved significantly in this group. Diameter of islet of Langerhans (μm), area occupied by β-cell/ islet of Langerhans (μm 2) and number of β-cells/islet of Langerhans were amazingly improved to the NC animals. Expressions of mRNA for SOD1 and CAT from liver tissue have been found to be increased multifold while GPx was remained unchanged. The data suggests that L. macrophylla root extract could be very potential as functional food to modulate pancreatic action.
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