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Pharmacological and therapeutic importance of hibiscus sabdariffa-A review

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Abstract

The phytochemical analysis of Hibiscus sabdariffa showed that the plant contained alkaloids, anthocyanins, flavonoids, phenols, saponins, tannins, polyuronides, cardiac glycosides, reducing sugar, carbohydrate, protein, gums, mineral, essential and volatile oils. The recent pharmacological studies showed that Hibiscus sabdariffa possessed antibacterial, antifungal, antiviral, anticancer, apoptotic, immunological, antioxidant, hypolipidemic, antidiabetic, smooth muscle relaxant, gastrointestinal antiinflammatory, analgesic, antipyretic, protective effects, wound healing, and wide range of cardiovascular and CNS effects. The current review discussed the chemical constituent, pharmacological and therapeutic effects of Hibiscus sabdariffa.
451|International Journal of Pharmaceutical Research | Apr-june 2018 | Vol 10 | Issue 3
Review Article
Pharmacological and therapeutic importance of
Hibiscus sabdariffa- A review
ALI ESM AIL AL-SN AFI
Department of Pharmacology,College of Medicine, University of Thi qar, Iraq.
(m): +9647801397994. E mail id :aboahmad61@yahoo.com
Received: 27.04.18, Revised: 27.05.18, Accepted: 27.06.18
ABSTRACT
The phytochemical analysis of Hibiscus sabdariffa showed that the plant contained alkaloids, anthocyanins, flavonoids,
phenols, saponins, tannins, polyuronides, cardiac glycosides, reducing sugar, carbohydrate, protein, gums, mineral,
essential and volatile oils. The recent pharmacological studies showed that Hibiscus sabdariffa possessed antibacterial,
antifungal, antiviral, anticancer, apoptotic, immunological, antioxidant, hypolipidemic, antidiabetic, smooth muscle
relaxant, gastrointestinal antiinflammatory, analgesic, antipyretic, protective effects, wound healing, and wide range of
cardiovascular and CNS effects. The current review discussed the chemical constituent, pharmacological and therapeutic
effects of Hibiscus sabdariffa.
Keywords: Hibiscus sabdariffa,pharmacology, chemical constituents, therapeutic, pharmacognosy.
INTRODUCTION
Herbal medicine is the oldest form of healthcare
known to mankind. Herbs had been used by all
cultures throughout history. Plants are a valuable
source of a wide range of secondary metabolites,
which are used as pharmaceuticals, agrochemicals,
flavours, fragrances, colours, biopesticides and food
additives. Hibiscus (Hibiscus sabdariffa) has a long
history of use in Africa and neighboring tropical
countries for many conditions, including
hypertension, liver diseases, cancer, constipation,
and fever. Fresh or dried calyces of Hibiscus
sabdariffa were used in the preparation of herbal
drinks, hot and cold beverages, fermented drinks,
wine, jam, jellied confectionaries, ice cream,
chocolates, flavouring agents, puddings and cakes.
The recent studies revealed that Hibiscus sabdariffa
contains wide range of bioactive constituents and
possessed wide range of pharmacological effects.
The current review will highlight the chemical
constituent, pharmacological and therapeutic effects
of Hibiscus sabdariffa.
Plant profile
Synonyms
Abelmoschus cruentus (Bertol.) Walp., Furcaria
sabdariffa Ulbr., Hibiscus acetosus Noronha,
Hibiscus cruentus Bertol., Hibiscus fraternus L.,
Hibiscus gossypifolius Mill., Hibiscus palmatilobus
Baill., Hibiscus sanguineus Griff., Hibiscus sabdariffa
Rottb. and Sabdariffa rubra Kostel(1).
Taxonomic classification
Kingdom: Plantae, Subkingdom: Viridiplantae,
Infrakingdom: Streptophyta, Superdivision:
Embryophyta, Division: Tracheophyta, Subdivision:
Spermatophytina, Class: Magnoliopsida,
Superorder: Rosanae, Order : Malvales,
Family : Mavaceae, Genus : Hibiscus, Species:
Hibiscus sabdariffa(2).
Common names
Arabic
Chi Kujarat, Karkadah, Karkadeeb, Shi Sudani, Shi
El-Sudan; English: Indian-sorrel, Jamaica-sorrel,
Red-sorrel, Roselle, Sorrel; French: Oseille de
Guinée; German: Malventee, Rosella; Portuguese:
Carurú-de-Guiné, Quiabo-azedo, Quiabo-de-
Angola, Quiabo-róseo, Quiabo-roxo, Rosela,
Vinagreira; Spanish: Rosa de Jamaica, Serení;
Swedish: Rosellhibiskus(3).
Distribution
It was native to old world tropics, probably in the
East Indies or Africa, now cultivated throughout the
tropics(4-5). However, roselle may domesticated in
Western Sudan before 4000 BC, it was first
recorded in Europe in 1576 AD. It carried from
Africa to the New World by slaves for use as a food
plant. Roselle was called Jamaican sorrel in 1707 in
Jamaica, where the regular use of the calyces as
food seemed to have been first practiced. The use of
the plant was known in Java as early as 1658AD. In
the New World, roselle was cultivated in Mexico,
Central America, the West Indies, Southern Florida,
Texas and California in the late 19th century(6-8).
Now, it was said that Hibiscus sabdariffa is grown
in all parts of the world(9).
Description
The plant is an annual erect shrub, it can also be
regarded as a perennial. Culinary varieties are
many-branched, bushy, and generally 1–2 m tall.
Stems may be green or red, depending on the seed
source. It has a strong taproot. The young plants
have leaves that are unlobed, but as the plant grows
the later-developing leaves are shallowly to deeply
palmate, 3- or 5-parted (up to 7-parted). The large
flowers have pale yellow petals (may suffused with
pink or red) and a dark red eye. The flowers are
Ali et al / Pharmacological and therapeutic importance of Hibiscus sabdariffa- A review
452|International Journal of Pharmaceutical Research | Apr-june 2018 | Vol 10 | Issue 3
usually borne singly in the leaf axils. The sepals at
the base of the large flowers and fruit vary from
dark purple to bright red (may white) at maturity.
The calyx increases from 1 to 2 cm in length before
the flower is fertilized, then it reaches 5.5 cm
(occasionally longer) at maturity. Flowers are red to
yellow, with a dark center containing short
peduncles, and have both male and female organs.
The seed pods begin ripening near the bottom and
proceed to the top(10-13).
Traditional uses
Hibiscus has a long history of use in Africa and
neighboring tropical countries for many conditions,
including hypertension, liver diseases, cancer,
constipation, and fever. Fresh or dried calyces of
Hibiscus sabdariffa were used in the preparation of
herbal drinks, hot and cold beverages, fermented
drinks, wine, jam, jellied confectionaries, ice cream,
chocolates, flavouring agents, puddings and
cakes(14-17)Roselle was used as herbal tea to
sooth colds, clear a blocked nose, clear mucous, as
an astringent, promoting kidney function, aiding
digestion, as a general tonic, diuretic, and
antipyretic(10).Hibiscus sabdariffa was also used as
folk remedy for abscesses, cancer, cough, debility,
dyspepsia, dysuria, fever, hangover, heart ailments,
neurosis, scurvy and strangury(18).In Mexico, India
and Africa infusions of the leaves or calyces were
traditionally used as diuretic, cholerectic, febrifugal
and hypotensive, to decrease the viscosity of the
blood and to stimulate intestinal peristalsis. In
India, a decoction from the seeds was used to
relieve pain in urination and indigestion. In Chinese
folk medicine, it is used to treat liver disorders and
high blood pressure(10, 19) In North Africa, calyces
preparations were used to treat sore throats,
coughs, and emollient leaf pulp was used for the
treatment of external wounds and abscesses(20).In
Nigeria, a decoction of the seeds was used
traditionally to enhance or induce lactation in cases
of poor milk production and poor letdown(9). In
Iraq, a decoction was used as digestive, diuretic,
sedative and refresher(21). In Iran, sour hibiscus
tea was reportedly a traditional treatment for
hypertension(22). In Uganda, Hibscus sabdariffa
was used in anemic and sick individuals to improve
their health and as an immune booster(23).
Parts used
Calyces, seeds, leaves, shoots and oil(14).
Physicochemical characteristics
The yield of the extracted oil from red and white
Hibiscus sabdariffa seeds was found to be 21.1%.
The oil had a refractive index (1.467, 1.466),
saponification value (189.7, 189.1), iodine value
(119, 119), peroxide value (4.6, 4.7), acid value
(3.57, 3.55), viscosity (22.5, 22.5) and specific
gravity (0.90, 0.90) for oil of red and white Hibiscus
sabdariffa seeds, respectively (24-25).
Chemical constituents
The preliminary phytochemical analysis of Hibiscus
sabdariffa showed that the different parts of the
plant contained alkaloids, anthocyanins, flavonoids,
phenols, saponins, tannins, polyuronides, cardiac
glycosides, reducing sugar, carbohydrate, protein,
gums, mineral, essential and volatile oils(9,26-30).
Quantitative determination of the phytochemical
constituents showed that calyces contained
saponnins 0.009-0.96%, flavonoids 0.43-20.08%,
tannins 0.158-17.00%, phenols 0.26-1.10%,
glycosides 0.132% and alkaloids 2.14%(31-
33).Analysis of Hibiscus sabdariffa petals showed
the presence of anthocyanins 16.53 mg/g, phenols
7.40 mg/g and flavonoids 3.50 mg/g (12.76
%)(26).The anthocyanins determined in calyx and
callus of Hibiscus sabdariffa were (mg/g):
cyanidin-3-O-glucoside 02.40 ± 0.02 and 08.01
± 0.04, delphinidin-3-O-glucoside 02.20 ± 0.01
and 27.04 ± 0.07, Cyanidin-3-O-sambubioside
17.11 ± 0.10 and 53.93 ± 0.20, delphinidin-3-
O-sambubioside 21.28 ± 0.05 and 07.07 ± 0.05,
malvidin-3-O-glucoside (not detected) and 18.19
± 0.10, petunidin-3-O-glucoside (not detected) and
16.89 ± 0.02 respectively. The sum of the amounts
of anthocyanins was 42.99 ± 0.70 and 131.13 ±
1.50 respectively(34-35).The phytochemical study of
the calyces of Hibiscus sabdariffa revealed
identification of 10 compounds phenolic acids
(protocatechuic acid and chlorogenic acid);
flavonoids (eugenol, gossypetin, kaempferol,
quercetin, myricetin, luteolin, rutin and
astragalin)(36). Eighteen phenolic compounds were
identified Hibiscus sabdariffa petals included
chlorogenic acid , protocatechuic acid,
gossypetrin, sabdaretin, gossypetin, luteolin,
gossytrin, hibiscetin, rutin, hibiscetrin, myricetin,
eugenol, nicotiflorine, quercitrin, quercetin,
kaempferol, astragalin and cyranoside(26).Hibiscus
sabdariffa extracts contained organic acids,
including citric acid, hydroxycitric acid, hibiscus acid,
malic acid tartaric acid, oxalic acid and ascorbic
acid(14,37). Organic acids amounts of Hibiscus
sabdariffa calyces were: malic: 560 ± 13, citric
acid: 70 ± 2.5, tartaric acid: 46 ± 2.6, oxalic acid:
148 ± 7.2 and acetic acid: 115 ± 5.5 mg/100g
calyces(33). Nutritional analysis showed that the
fresh calyces of Hibiscus sabdariffa contained
protein 1.9 g/100 g, fat 0.1 g/100 g, carbohydrates
12.3 g/100 g, fiber 2.3 g/100 g, vitamin C 14
mg/100 g, β-carotene 300 μg/100 g, calcium 1.72
mg/ 100 g, iron 57 mg/100 g, Mg 322.2±2.4
mg/g, K 1505±7.2 mg/g, Al 46±1.0 mg/g, Na
12.5±1.3 mg/g, Mn 7.6±10 mg/g and Cl
24.5±30 mg/g. The leaves contained protein 3.3
g/100 g, fat 0.3 g/100 g, carbohydrate 9.2 g/100
g, phosphorus 214 mg/100 g, iron 4.8 mg/100 g
thiamine 0.45 mg/100 g, β-carotene 4135 µg/100
g, riboflavin 0.45 mg/100 g and ascorbic acid 54
Ali et al / Pharmacological and therapeutic importance of Hibiscus sabdariffa- A review
453|International Journal of Pharmaceutical Research | Apr-june 2018 | Vol 10 | Issue 3
mg/100 g. The seeds contained crude protein
27.78%, crude fatty oil 21.85%, carbohydrate
21.25%, crude fiber 16.44%, potassium 1329 ±
1.47 mg/100 g, sodium 659 ± 1.58 mg/100 g,
calcium 647 ± 1.21 mg/100 g, phosphorus 510 ±
1.58mg/100 g, magnesium 442.8 ± 1.80 mg/100
g(38-40). The amino acid composition of Hibiscus
sabdariffa calyx (mg/g dry matter) were: arginine
3.60- 4.48, cysteine 0.87-1.30, histidine 1.19-1.50,
isoleucine 2.70-3.00, leucine 4.21-5.00, lysine
2.77-3.90, methionine 0.65-1.00, phenylalanine
2.32-3.20, threonine 2.36-3.00, tryptophane -
0.45, tyrosine 1.44-2.20, valine 3.33-3.80,
aspartame 10.50-16.30, glutamine 7.20- 8.85,
alanine 3.46-3.70, glycine 2.47-3.80, proline 5.60-
5.82 and serine 2.65-3.50(41,19).The components
of the essential oils of air-dried flowers of Hibiscus
sabdariffa from Lagos- Nigeria, were analysed by
means of gas chromatography (GC) and gas
chromatography coupled with mass spectrometry
(GCMS). The major compounds identified in the
essential oil were hexadecanoic acid (64.3%) and
linoleic acid (22.7%).The chemical classes of
compounds present in the oil were sesquiterpene
hydrocarbon (0.2%), oxygenated sesquiterpenes
(1.2%), diterpenes (1.6%), aliphatic compounds
(0.6%), phenyl propanoids (0.1%) and fatty acids
(96.1%). Seventeen compounds were identified in
the oil included (%): n-nonanoic acid: 0.6, eugenol
0.1, β-caryophyllene: 0.1, 10-epi-γ-eudesmol: 0.3,
Ϯ-cadinol: 0.5, α-selina-6-en-4-ol: 0.2, bisabolol
oxide: 0.2, cadalene: 0.1, tetradecanoic acid: 2.1,
hexadecanoic acid methyl ester:2.3, isophytol: 1.6,
hexadecanoic acid: 64.3, heptadecanoic acid: 1.2,
linoleic acid methyl ester: 2.1, oleic acid: 0.9,
stearic acid methyl ester: 0.5 and linoleic acid:
22.7(42).Oils of Hibiscus sabdariffa flowers from
Iraq contained palmitic (0.27%) and Linoleic (0.7%)
acids. Where H2 (saponified of chloroform extract
and methylation) s contained palmitic (0.04%),
linoleic (0.004%), stearic (0.008%), heptanoic
(0.003%) and octanoic (0.011%) acids(43).The main
unsaturated fatty acids in the oil of the seed of red
and white Hibiscus sabdariffa from the North
Kordofan, Sudan were oleic (47.0555%,
47.8868%), linoleic (30.5836%, 30.7931%) and
elaideic acid (14.359%, 15.1603%) and the
saturated acids are palmitic acid (3.9494%,
3.9198%) and myristic acid (1.9609%,
1.9845%)(24). The analysis of seed oil of Hibiscus
sabdariffa petroleum ether extract using gas
chromatography (GC) revealed the presence of
linolelaidic acid (26.02%), arachidic acid (20.59%)
and palmitic acid (16.05%)(44).Chemical classes
isolated from the oil of tea of roselle (Hibiscus
sabdariffa) from Havana - Cuba, were included
terpenoids which comprised the largest class of
volatiles 48.2 %, fatty acids 12.4 %, alcohols 8.6 %,
phenols 6.6 %, esters 3.9 %, furanoids 3.8 % and
others 16.3 %. Eighty-one volatile constituents were
identified from the oil of Hibiscus sabdariffa, the
major constituents were linalool (0.58 mg/kg) and
α-terpineol (0.55 mg/kg). However the componuds
identified and their percentage were: 2,3-
dimethylbutane < 0.01, isobutanol 0.15, 2-
pentanone < 0.01, 2-methylbutanal 0.06, 3-
methyl-1-butanol 0.14, 2-methyl-1-butanol 0.06,
isobutanoic acid 0.01, 2-ethylfuran 0.03, hexanal
0.12, 2-furfural 0.13, 2-methylbutanoic acid 0.02,
(E)-2-hexenal 0.02, 2-furfuryl alcohol 0.02, (Z)-3-
hexen-1-ol 0.02, a-angelica lactone 0.04, p-xylene
< 0.01, heptanal 0.02, 2-acetylfuran 0.02, (E)-2-
heptenal 0.03, benzaldehyde 0.03, 5-methyl-2-
furfural < 0.01, 2,2,6-trimethyl-6-vinyl tetrahydro
furan 0.13, pentyl propanoate 0.02, methyl-2-
furoate 0.03, 1-octen-3-ol 0.05, 6-methyl-5-hepten-
2-one 0.02, octanal 0.03, a-terpinene 0.01, p-
cymene 0.02, limonene 0.07, (Z)-b-ocimene 0.02,
1-propylbenzene 0.05, (E)-b-ocimene 0.06,
acetophenone < 0.01, octanol 0.03, cis -linalool
oxide (furanoid form) 0.36, m-cymenene < 0.01,
trans -linalool oxide (furanoid form) 0.29, linalool
0.58, nonanal 0.16, 2-phenethyl alcohol 0.01,
myrcenol 0.03, cis -b-terpineol 0.03, (E)-2-nonenal
0.05, ethyl benzoate 0.01, terpinen-4-ol 0.08, p-
cymen-8-ol 0.06, a-terpineol 0.55, methyl salicylate
0.05, decanal 0.05, p-menthen-9-al 0.08,
thymoquinone 0.14, geraniol 0.10, decanol 0.03,
(E)-anethole 0.06, 1-methylnaphthalene 0.02,
indole 0.04, undecanal 0.02, 4-vinylguaiacol 0.04,
(E.E)-2,4-decadienal 0.03, methyl decanoate 0.02,
methyl anthranilate 0.02, 1,2-dihydro-2,5,8-
trimethylnaphthalene 0.02, eugenol 0.23, methyl
eugenol 0.07, 2,6-dimethyl naphthalene 0.04, b-
caryophyllene 0.04, a-humulene 0.02, geranyl
acetone 0.02, b-santalene 0.02, a-calacorene
0.07, (E)-nerolidol 0.15, dodecanoic acid 0.15, g-
eudesmol 0.12, tetradecanoic acid 0.13,
pentadecanoic acid 0.04, methyl hexadecanoate
0.04, (Z)-9-hexadecenoic acid 0.19, (E)-phytol 0.04,
hexadecanoic acid 0.21 and (E)-phytol acetate
0.09(45).
Pharmacological effects
Antibacterial and antifungal effects
Extracts and fractions of Hibiscus sabdariffa were
tested against some pathogenic bacteria of human
[Gram positive (Corynebacterium diphtheria,
staphylococcus aureus, staphylococcus capitis), and
Gram negative (Pseudomonas aurogenosa and
protus merabeles)], from the all extracts, the fraction
of (Chloroform-Ethanol) gave the highest effect, it
gave inhibition range: (26-34 mm)(43). The
antimicrobial activity of the roselle water and
ethanol extracts was tested against Bacillus subtilis
(ATCC6633), Staphylococcus aureus (ATCC6538)
and Escherichia coli (ATCC 8739). The inhibition of
the roselle ethanol extract against B. subtilis and S.
Ali et al / Pharmacological and therapeutic importance of Hibiscus sabdariffa- A review
454|International Journal of Pharmaceutical Research | Apr-june 2018 | Vol 10 | Issue 3
aureus was slightly higher than that of
water extract but this difference was not significant.
However, E. coli was strongly inhibited by the
Roselle water extract at concentrations of 25 and 50
mg/ml(46). The antibacterial effects of Hibiscus
sabdariffa calyces extracts were evaluated against
Escherichia coli (ATCC 25922), Pseudomonas
aeruginosa (ATCC 27853), Klebsiella pneumoniae
(ATCC 15380), Haemophilus influenzae (ATCC
10211), Staphylococcus aureus (ATCC 25923),
Streptococcus pyogenes (ATCC 12344) and
Streptococcus pneumoniae (ATCC 6305). The zone
of growth inhibition exerted by the ethanolic extract
of calyces against Pseudomonas aeruginosa (ATCC
27853): 15mm , Klebsiella pneumoniae (ATCC
15380): 27mm , Haemophilus influenzae (ATCC
10211):20mm , Staphylococcus aureus (ATCC
25923): 29mm, Streptococcus pneumoniae (ATCC
6305): 29mm. The zone of growth inhibition exerted
by the ethyl acetate of calyces: Escherichia coli
(ATCC 25922): 11mm, Streptococcus pyogenes
(ATCC 12344): 11mm. The zone of growth
inhibition exerted by the methanolic extract of
calyces against Escherichia coli (ATCC 25922):
16mm, Pseudomonas aeruginosa (ATCC
27853):29, Klebsiella pneumoniae (ATCC 15380):
28, Haemophilus influenzae (ATCC 10211): 27,
Staphylococcus aureus (ATCC 25923): 25,
Streptococcus pyogenes (ATCC 12344): 34mm. The
zone of growth inhibition exerted by the aqueous
extract of calyces against Escherichia coli (ATCC
25922): 30mm, Pseudomonas aeruginosa (ATCC
27853): 31mm, Klebsiella pneumoniae (ATCC
15380): 22mm, Haemophilus influenzae (ATCC
10211): 25mm, Staphylococcus aureus (ATCC
25923): 23mm, Streptococcus pyogenes (ATCC
12344): 20mm and Streptococcus pneumoniae
(ATCC 6305): 19mm(47).The antimicrobial
potential of leaves and seeds methanolic extracts of
Hibiscus sabdariffa was studied against Gram-
positive, Gram-negative bacteria and fungal strains.
Leaves methanolic extracts of Hibiscus sabdariffa
possessed antibacterial effects against Gram-
positive bacteria (Bacillus subitilis NCTC: 8236 and
Staphylococcus aureus ATCC: 25923), as well as
Gram-negative bacteria (Escherichia coli ATCC:
25922, Pseudomonas aeruginosa ATCC: 27853,
Klebsiella pneumoniae ATCC: 53657 and Proteus
vulgaris ATCC: 6380). The leaves methanolic
extracts of Hibiscus sabdariffa also showed an
intermediate antifungal activity against two
reference fungal strains (Candida albicans ATCC:
7596 and Aspergillus niger ATCC: 9765). The seeds
methanolic extracts of Hibiscus sabdariffa did not
show any activity against the tested bacterial and
fungal strains(48).The antibacterial activity of
methanol extract of Hibiscus sabdariffa calyces was
studied against five hospital isolates of multidrug
resistant Acinetobacter baumannii (MDR A.
baumannii). The methanol extract exhibited
significant antibacterial properties against the non-
MDR A. baumannii as well as the MDR A. baumannii
strains with a zone of inhibition ranging from (11.3
± 0.3) to (13.6 ± 0.3) mm. Values of minimum
inhibitory concentration and minimum bactericidal
concentration ranged from 25 to 50 and 50 to 100
mg/ml, respectively. The percentage inhibition of
Hibiscus sabdariffa extract (10 mg/disc) with respect
to gentamicin (10 mg/disc) revealed that Hibiscus
sabdariffa was much more effective than
gentamicin(49).The antimicrobial potency of
Hibiscus sabdariffa leaf extracts were evaluated
against Klebsiella pneumonia,Salmonella typhi and
Shigella dysenteriae. Mean zones of inhibition of
the aqueous leaf extracts for the 20 and 40 mg/ml
for K. pneumonia was (15.33±0.58 and
18.67±0.76), S. typhi (15.50±0.50 and
16.33±0.58) and S. dysenteriae (17.83±0.76 and
19.17±1.04). Hexane extracts showed no activity
against the test organisms. The minimum inhibitory
concentration and the minimum bactericidal
concentration for the aqueous leaf extract were: K.
pneumonia (10.0 and 15.5 mg/ml), S. typhi (10.0
and 12.5 mg/ml) and S. dysenteriae (7.5 and 12.5
mg/ml) respectively(50). The antimicrobial activity of
concentrations of 10%, 5%, and 2.5% methanol
extract of Hibiscus sabdariffa was studied against
Escherichia coli O157:H7 isolates from food,
veterinary, and clinical samples. The results revealed
that the most potent concentration was 10%, then
5%, and finally 2.5%. The overall mean zone of
inhibition for the Hibiscus sabdariffa extract was
12.66 mm for 10%, 10.75 mm for 5%, and 8.9 mm
for 2.5%. The highest inhibition zones (11.16 mm)
were observed against veterinary samples, and the
lowest (10.57 mm) against the food samples(51).
Aqueous extracts from the dried calyces of Hibiscus
sabdariffa was tested for antimicrobial activity
against the foodborne pathogens Escherichia coli
O157:H7 strains ATCC 43894 and Staphylococcus
aureus strains SA113 and ATCC 27708. Against E.
coli, the results of 20 mg/ml filtered extract were not
different from those of the control, whereas
autoclaved extracts reduced viable cells ca. 3 to 4
log CFU/ml. At 60 mg/ml, both extracts inactivated
cells after 24 h. There were reduced populations of
both strains of S. aureus (ca. 2.7 and 3 log CFU/ml,
respectively) after 24 h of incubation in 40 mg/ml
filtered extracts(52).The methanol extract of the
dried calyces of Hibiscus sabdariffa were
investigated for antibacterial activity against Gram
positive and Gram negative bacteria. The highest
antibacterial activity of Hibiscus sabdariffa calyces
was recorded against S. aureus (18.5 ± 0.5 mm),
followed by S. epidermidis (17.5 ± 1.5 mm), S.
enteric (17.5 ± 1.5 mm), K. pneumonia (17.5 ± 0.5
mm), P. aeruginosa (15.5 ± 0.5 mm), E.
coli(14.5±0.5 mm), P. vulgaris (14.5±0.5 mm),
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455|International Journal of Pharmaceutical Research | Apr-june 2018 | Vol 10 | Issue 3
and B. cereus (13.5 ± 1.5 mm)(53).The
antimicrobial combinatory effect of the
aqueous extract of Hibiscus sabdariffa (AEHS) with
antibiotics (clarithromycin, amoxicillin,
metronidazole) were evaluated against Helicobacter
pylori strains. AEHS exerted remarkable
bacteriostatic effect against all Helicobacter pylori
tested strains with MICs values ranging from 9.18 to
16.68 μg/ml. Synergy effect of aqueous extract of
Hibiscus sabdariffa with clarithromycin or
metronidazole was obtained against four of seven
Helicobacter pylori strains tested with ∑FIC ranging
from 0.21 to 0.39. The additive effect of
aqueous extract of Hibiscus sabdariffa with
amoxicillin was obtained against five of seven
Helicobacter pylori strains tested with ∑FIC ranging
from 0.61 to 0.91(54).
The antifungal effect of Hibiscus sabdariffa extract
was evaluated against Candida albicans, the biofilm
forming capacity of Candida albicans strains in the
present of the Hibiscus sabdariffa extract was also
studied. The minimum inhibitory concentration
values of Hibiscus sabdariffa extract were ranged
from 0.5 to 2.0 mg/ml. Time-kill experiment
demonstrated that the effect was fungistatic.
Furthermore, Hibiscus sabdariffa extract inhibited
biofilm production of all the isolates(55).The
antifungal effect of Hibiscus sabdariffa extract, in
combination with voriconazole or fluconazole was
evaluated against C. albicans isolates. Six strains of
fluconazole-resistant C. albicans isolates were
obtained from patients with recurrent candiduria.
When the extract was used in combination with
voriconazole, a high degree of synergism was
observed(56).
Antiviral activity
The antiviral effects of aqueous extracts of Hibiscus
sabdariffa (HE) was studied against human
norovirus surrogates (feline calicivirus (FCV-F9) and
murine norovirus (MNV-1)) and hepatitis A virus
(HAV) at 37 °C over 24 h. FCV-F9 titers were
reduced to undetectable levels after 15 min with
both 40 and 100 mg/ml HE. MNV-1 was reduced
by 1.77 ± 0.10 and 1.88 ± 0.12 log PFU/ml after
6 h with 40 and 100 mg/ml HE, respectively. HAV
was reduced to undetectable levels by both HE
concentrations after 24 h(57). The
aqueous extract of Hibiscus sabdariffa (AEHS) and
its bioactive constituent protocatechuic acid (PCA),
were evaluated in vitro for their antiviral activity
against HSV-2 clinical isolates and anti-enzymatic
activity against urease. PCA showed potent anti-
HSV-2 activity compared with that of acyclovir, with
EC50values of 0.92 and 1.43 µg/ml, respectively,
and selectivity indices > 217 and > 140,
respectively. AEHS exerted anti-urease activity, with
an IC50 value of 82.4 µg/ml(58). The antiviral
effects of aqueous Hibiscus sabdariffa extracts was
evaluated against Aichi virus (AiV) (a foodborne
pathogen that causes gastroenteritis). AiV did not
show any significant reduction with 1:1 (100 mg/ml)
or 1:5 (40 mg/ml) diluted aqueous hibiscus extracts
after 0.5, 1, or 2 h at 37 °C. However, AiV titers
were reduced to non-detectable levels after 24 h
with all the three tested concentrations. AiV was
reduced by 0.5 and 0.9 log PFU/ml with undiluted
extracts (200 mg/ml) after 2 and 6 h,
respectively(59). The leaves extracts of Hibiscus
sabdariffa (red and green leaved) were studied for
antiviral activities against Measles Virus (MV) as well
as the effects of the extracts on Hep-2 cells were
studied. Ethanol extract of the leaves showed no
toxicity to the Hep-2 cells at all concentrations used
(5, 10 and 15 mg/ml). The pre-inoculative
treatment of Hep-2 cells with plant extracts showed
that Hibiscus sabdariffa had antiviral activities only
at 10 and 15 mg/ml on MV. The post-inoculative
treatment of Hep-2 cells with plant extracts showed
that Hibiscus sabdariffa at 5, 10 and 15 mg/ml
concentrations, had antiviral activities on MV(60).
Anticancer and apoptotic effects
The anticancer effect of roselle juice were
evaluated using different cell lines like ovarian
(Caov-3), breast (MCF-7, MDA-MB-231) and
cervical (HeLa) cancer cell lines. It possessed the
strongest anti-proliferative potency towards the
MCF-7 cancer cells(61).The anticancer effect of
Hibiscus sabdariffa extract (HSE) was evaluated on a
panel of human tumor cell lines, multiple myeloma
(MM) cells (RPMI 8226) and oral squamous cell
carcinoma (OSCC) cells (SCC-25). In both RPMI
8226 and SCC-25 cells, HSE impaired cell growth,
exerted a reversible cytostatic effect, and reduced
cell motility and invasiveness(62). Human gastric
carcinoma (AGS) cells were susceptible to Hibiscus
polyphenol-rich extract (0.95 mg/ml HPE inhibited
its growth by 50%). AGS cells underwent DNA
fragmentation, and had an increase in the
distribution of hypodiploid phase (apoptotic peak,
52.36%) after a 24-h treatment with HPE (2.0
mg/ml). The effect of HPE on AGS cells might be
mediated via p53 signaling and p38 MAPK/FasL
cascade pathway, as demonstrated by an increase
in the phosphorylation of p53 and the usage of a
specific p38 inhibitor(63). The cytotoxic effects of
Hibiscus sabdariffa aqueous extract (HSE) against
human breast adenocarcinoma cell line (MCF-7)
and fetal foreskin fibroblast (HFFF) were
investigated. Different concentrations of water
extract of calyces were added and the percentage of
cell survival was determined after 24, 48, and 72
hours using an MTT assay. Apoptosis induction was
assessed by DNA fragmentation. At the
concentration of 0.5 mg/ml of the extract and after
72 hours incubation, the number of viable MCF-7
cells was less than 50%. The extract was not
cytotoxic against normal HFFF cells in all tested
concentrations. HSE induced apoptosis only in MCF-
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7 cells(64). The methanol extract from calyces of
Hibiscus sabdariffa showed significant selective
activity against a leukemia line (K-562), with IC50
values of 0.12-1.16 mg/ml, with concentration-
dependent, cytotoxic and cytocidal effects(65).The
cytotoxic activities of Hibiscus sabdariffa leave
extracts from different extraction methods were
tested against human prostate cancer cell line (PC-
3) using sulforhodamine B (SRB) assay. The results
showed that the 95% ethanolic extract of Hibiscus
sabdariffa dried leaves possessed potent cytotoxicity
against prostate cancer cell line with an IC50 of
8.58±0.68 μg/ml(66). The possible anticancer
effects of Hibiscus sabdariffa extract was studied
against human leukemic THP-1 cells. It exhibited a
concentration dependent antiproliferative effect
against THP-1 leukemic cells with IC50 values of
15.47 mg/ml(67).Roselle-anthocyanins (HA) showed
apoptosis of human cancer cells (HL-60) in a dose-
and time-dependent manner. It also increased
phosphorylation in p38, c-Jun and cytochrome c
release, and expression of tBid, Fas, and FasL
genes(68). Protocatechuic acid inhibited the survival
of human promyelocytic leukemia (HL-60) in a
concentration and time dependent manner. It
induced apoptosis via reduction of retinoblastoma
phosphorylation and down regulation of Bcl-2
protein expression. The cells underwent
intranucleosomal DNA fragmentation and
morphological changes characteristics of apoptosis,
while the action against gastric carcinoma cells by
inducing apoptosis was through JNK/MAPK
signaling pathways(69-70). Hibiscus sabdariffa leaf
extract (HLE) dose-dependently inhibited the
migration and invasion of human prostate cancer
LNCaP (lymph node carcinoma of the prostate) cells
under non-cytotoxic concentrations. HLE also
exerted an inhibitory effect on the activity and
expressions of matrix metalloproteinase-9 (MMP-9).
The HLE-inhibited MMP-9 expression appeared to
be a consequence of nuclear factor-kappaB (NF-κB)
inactivation because its DNA-binding activity was
suppressed by HLE. Molecular data showed that all
these influences of HLE might be mediated via
inhibition of protein kinase B (PKB, also known as
Akt) /NF-κB/MMP-9 cascade pathway, as
demonstrated by the transfection of Akt1
overexpression vector. The inhibitory effect of HLE
was proven by its inhibition on the growth of LNCaP
cells and the expressions of metastasis-related
molecular proteins in vivo(71). The anticancer
activity of Hibiscus leaf polyphenolic (HLP) extract
was studied against melanoma cells. HLP was rich
in epicatechin gallate (ECG) and other polyphenols.
The results revealed that both HLP and ECG induced
the caspases cleavages, Bcl-2 family proteins
regulation, and Fas/FasL activation in A375 cells. In
addition, The cells presented AVO-positive after HLP
treatments. The results indicated that the anticancer
effect of HLP, partly contributed by ECG(72). The
protective effect of anthocyanin extract of roselle
(HAs) was studied in N-nitrosomethylurea (NMU)-
induced leukemia of rats. Leukemia was induced by
intravenous injection of 35 mg/kg bw of NMU
dissolved in physiologic saline solution. HAs groups
received different doses of HAs (0.1 and 0.2%)
daily, orally, after NMU injection. After 220 days,
when compared with the NMU-only group, HAs
significantly prevented loss of organ weight and
ameliorated the impairment of morphology,
hematology, and histopathology. Treatment with
HAs caused reduction in the levels of AST, ALT, uric
acid, and MPO. Oral administration of HAs (0.2%)
also remarkably inhibited progression of NMU-
induced leukemia by approximately 33.3% in
rats(73). An in vivo micronucleus assay using albino
mice was used to examine the anticlastogenic effects
of a crude aqueous extract of Hibiscus sabdariffa
fruits in bone marrow cells of mice. Various doses of
freshly prepared crude extract of Hibiscus sabdariffa
(50, 100 and 150 mg/kg bw) were given for 7 days
as a dietary supplement followed by a single dose of
sodium arsenite (2.5 mg/kg bw). The results showed
that sodium arsenite effectively induced micronuclei
in polychromatic erythrocytes (PCEs). Administration
of a crude extract of Hibiscus sabdariffa significantly
reduced micronuclei in PCEs(74). The 80%
ethanol extract of Hibiscus sabdariffa, showed
antimutagenic and chemopreventive activity in
chemical induce colon carcinogenesis(74).The
Hibiscus sabdariffa extract inhibited mutagenicity of
1-nitropyrene (1-NP) in a dose-response manner.
The inhibition rate on HeLa cells of Hibiscus
sabdariffa extract was also dose-dependent. The
HAE did not induce DNA fragmentation(75). The
effect of Hibiscus sabdariffa aqueous extract was
investigated against cyclophosphamide (CPA,
25mg/Kg) induced damage to DNA in male wistar
rats by micronucleus test. The aqueous extract was
prepared by infusion and each animal received a
daily dose of 400mg/Kg by gavage for 15
consecutive days of treatment. The group treated
with the aqueous extract of Hibiscus sabdariffa
revealed a 91% reduction in micronucleus frequency
when compared with the positive control group(76).
Delphinidin 3-sambubioside (Dp3-Sam), (the
anthocyanin, isolated from the dried calices of
Hibiscus sabdariffa) induced a dose-dependent
apoptosis in human leukemia cells (HL-60) as
characterized by cell morphology, DNA
fragmentation, activation of caspase-3, -8, and -9,
and inactivation of poly(ADP)ribose polymerase
(PARP). Dp3-Sam induced Bid truncation,
mitochondrial membrane potential (Δ
Ψ
m) loss, and
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cytochrome crelease from mitochondria to cytosol.
Dp3-Sam also caused a time- and dose-dependent
elevation of intracellular reactive oxygen species
(ROS) level in HL-60 cells, and antioxidants such as
N-acetyl-l-cysteine (NAC) and catalase could
effectively block Dp3-Sam-induced ROS generation,
caspase-3 activity, and DNA fragmentation(77).The
chemopreventive properties of Hibiscus sabdariffa
on human gastric carcinoma cells were investigated.
With the using of a set of apoptotic detection assays,
it appeared that HSE induced cytotoxicity and
apoptosis of AGS cells in a concentration-dependent
manner but was ineffective in Chang liver cells. The
result also revealed increased phosphorylation in
p38, JNK and c-Jun, cytochrome crelease, and
expression of Fas, FasL, Bax, and t-Bid in the HSE-
treated AGS cells. The results indicated that HSE
mediated AGS apoptosis via the JNK/p38 signaling
cascade(78). Hibiscus anthocyanins (HAs) inhibited
the serum-stimulated proliferation of smooth muscle
cell (SMC) and resulted in cell apoptosis. The HAs
inducing cell apoptosis was dose dependent. HAs
induced apoptosis via activating p38 MAP kinase
that subsequently phosphorylates target protein c-
Jun and transduces the signal to further activate the
apoptotic protein cascades that contain Fas-
mediated signaling (Fas/caspase-8 signaling
module) and activating p53 and inducing bax
expression(79).
Cardiovascular effects
Hibiscus sabdariffa crude extract induced
endothelium-dependent relaxant effects on isolated
thoracic aorta of male Wistar rats. The endothelium-
dependent relaxations were resulted from NOS
activation(80). Roselle calyx infusion was found to
lower significantly (P<0.05) both systolic and
diastolic pressure in spontaneously hypertensive and
normotensive Wistar-Kyoto rats at doses of 500 and
1000 mg/ kg bw. The reduction in blood pressure in
both groups was positively correlated with
weight(81). The aqueous extract of Hibiscus
sabdariffa calyx attenuated the development of salt-
induced hypertension in Sprague-Dawley rats
treated for 12 weeks(82-83) The aqueous extract of
petals of Hibiscus sabdariffa (HS) also attenuated
the established stages of 2-Kidney, 1-Clip
renovascular hypertension in Sprague-Dawley
rats(84). Hibiscus sabdariffa ingestion in rat (10%,
15% and 20% of the water extract in drinking water
for 10 consecutive weeks) significantly reduced
Systolic (SBP), diastolic (DBP) and left ventricles (LV)
mass in a dose-dependent fashion but did not affect
the heart rate. It significantly increased surface area
and length density of myocardial capillaries by 59%,
65% and 86%, and length density by 57%, 77% and
57%, respectively(85).The effect of roselle extract
(HSE) (100 mg/kg/bw HSE, orally for 21
consecutive days)on blood pressure, serum lipid
profile, oxidative stress marker levels and
histological changes to the heart induced by
nicotine (0.6 mg/kg/bw) were studied in rats. HSE
significantly (P>0.05) reduced the heart rate but
without effect on blood pressure. HSE increased the
high-density lipoprotein concentration significantly
(P<0.05) in nicotine- treated rats, without any
significant changes in total cholesterol, triglyceride
and low-density ipoprotein concentration. HSE
treatment was also found to reverse
malondialdehyde level, superoxide dimustase
enzyme activity and protein concentration
significantly (P<0.05) in nicotine-treated rats(86).
The anti-hypertensive activity of aqueous calyx
extract of Hibiscus sabdariffa was investigated on
salt induce hypertensive albino rats for 28 days. The
extract treated groups showed a significant (P<0.01)
reduction in diastolic and systolic blood pressure
when compared to the normotensive and
hypertensive rats. There was no significant
difference (P>0.05) between the drug treated and
the extract treated groups during this treatment(87).
Intravenous injection of aqueous extract of Hibiscus
sabdariffa calyces to anaesthetized cats lowered the
blood pressure in a dose-response manner. The
inhibitory effects were resistant to a number of
standard receptor blockers but the hypotensive
influence was partially blocked by atropine(88).In a
clinical study on hypertensive subjects, it was found
that roselle reduced the mean arterial pressure,
comparable to the effect of captopril(89).The daily
consumption of extract of hibiscus sepals
significantly decreased systolic and diastolic blood
pressure in adults with pre to moderate essential
hypertension and type 2 diabetes. The results
revealed that the effectiveness of extract was
equivalent to captropril, but less effective than
lisinopril(90). A controlled and randomized clinical
trial was carried out to compare the antihypertensive
effectiveness and tolerability of a
standardized extract from Hibiscus sabdariffa with
captopril. Patients with diagnosed hypertension and
without antihypertensive treatment for at least 1
month were included, they were recieved either an
infusion prepared with 10 g of dry calyx from
Hibiscus sabdariffa (9.6 mg anthocyanins content),
daily before breakfast, or captopril 25 mg twice a
day, for 4 weeks. The results showed that Hibiscus
sabdariffa was able to decrease the systolic blood
pressure (BP) from 139.05 to 123.73mm Hg
(P<0.03) and the diastolic BP from 90.81 to
79.52mm Hg (P<0.06). At the end of the study,
there were no significant differences between the BP
detected in both treatment groups (P>0.25). The
rates of therapeutic effectiveness were 0.7895 and
0.8438 with Hibiscus sabdariffa and captopril,
respectively (P>0.560), whilst the tolerability was
100% for both treatments(89). A randomized,
double-blind, placebo-controlled clinical trial was
conducted to determine the antihypertensive effects
of Hibiscus sabdariffa tea consumption on 65 pre-
and mildly hypertensive adults with no blood
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pressure-lowering medications. They used either
three 240-ml servings/day of brewed hibiscus tea or
placebo beverage for 6 wk. At 6 wk, hibiscus tea
lowered systolic BP (SBP) compared with placebo.
Diastolic BP was also lower, although this change
did not differ from placebo. The change in mean
arterial pressure was of borderline significance
compared with placebo. Participants with higher SBP
at baseline showed a greater response to hibiscus
treatment(91). Polyphenols from Hibiscus sabdariffa
calices were administered to patients with metabolic
syndrome (125 mg/kg/day for 4 wk) and
spontaneously hypertensive rats (125 or 60 mg/kg
in a single dose or daily for 1 wk). Hibiscus
sabdariffa extract improved metabolism, displayed
potent anti-inflammatory and antioxidant activities,
and significantly reduced blood pressure in both
humans and rats(92). Clinical trials confirmed the
antihypertensive effect of the watery infusions. The
results showed that the treatment decreased blood
pressure (BP) from 146.48/97.77 to 129.89/85.96
mmHg, reaching an absolute reduction of
17.14/11.97 mmHg (11.58/12.21%, P<0.05). The
treatment showed therapeutic effectiveness of 65.12
% as well as tolerability and safety of 100 %. BP
reductions and therapeutic effectiveness were lower
than those obtained with lisinopril (P<0.05)(93). The
antihypertensive activity of roselle could be
mediated by many mechanisms included inhibition
of angiotensin-converting enzyme activity and
subsequent renin-angiotensin-aldosterone system,
(especially anthocyanins delphinidin-3-O-
sambubioside, cyanidin-3-O-sambubioside and
related flavonoid glycosides), enhancement of
vascular activity by Na+ -K+ -ATPase and Ca2+-
Mg2+-ATPase, enhancement of NO production,
as endotheliumderived relaxing factor (EDRF),
attenuation of the discharge of the sympathetic
nervous system and diuretic effects(94-102).
Effects on lipid profile and body weight
The hypolipidemic effect of ethanolic extract of the
leaves of Hibiscus sabdariffa (HSEE) (100, 200, and
300 mg/kg) was investigated in hyperlipidemic rats.
Administration of HSEE (200 mg/kg and 300
mg/kg) together with continuous cholesterol feeding
for four weeks caused significant reduction in serum
cholesterol level by 18.5% and 22%, respectively
(P<0.05); serum triglyceride level by 15.6% and
20.6%, respectively (P<0.05); serum LDL level by
24% and 30%, respectively (P<0.05), and serum
VLDL level by 15.5% and 20.5%, respectively
(P<0.05), as compared to cholesterol group.
However, no significant change in HDL level was
observed(103). The effect of Hibiscus sabdariffa
dried calyx ethanolic extract on the serum lipid
profile was studied in Sprague-Dawley rats. The
rats were fed during 4 weeks with either a basal
diet, containing high cholesterol (1%), cholic acid
(0.25%), lard oil (10%), or a supplemental diet with
Hibiscus sabdariffa extract at 5%, 10%, and 15%
levels (SD5, SD10, SD15). Weight gain and faeces
dry weight were both very significantly less (P< or =
0.01) in SD10 and SD15 groups as compared to
the control group. Triacylglycerols and LDL levels
were both significantly less (P< or = 0.05) in all
groups (SD5, SD10, and SD15) as compared to the
control. For total lipids, SD10 and SD15 showed
significantly lower levels (P< or = 0.05), whereas
very significant differences (P< or = 0.01) were
observed in SD5 group. All groups had lower
cholesterol levels compared to controls; however,
only the SD5 group was statistically significant (P<
or = 0.05)(104). The effects of Hibiscus sabdariffa
calyx aqueous extract on the serum cholesterol,
body weight and liver marker enzymes activities
were studied in normal albino rats. The aqueous
extract was orally administered (100 800 mg/kg
bw for 28 days) to normal male albino rats. Hibiscus
sabdariffa administration significantly reduced
serum cholesterol and body weight in a dose and
duration dependent pattern(105). The
hypolipidemic and antiatherosclerotic effects of
Hibiscus sabdariffa extract (HSE) were investigated
in rabbits with experimental atherosclerosis. Rabbits
were fed with a normal diet, high cholesterol (1.3%),
lard oil (3%) diet (HCD) with or without 0.5 or 1%
HSE for 10 weeks. The levels of triglyceride,
cholesterol, and low-density lipoprotein cholesterol
(LDL-C) were decreased in the serum of rabbits fed
HCD plus HSE than in the serum of rabbits fed
HCD. Feeding HSE (0.5 and 1% in the diet) to
rabbits significantly reduced severe atherosclerosis
in the aorta. Histopathological examination showed
that HSE reduced foam cell formation and inhibited
smooth muscle cell migration and calcification in the
blood vessel of rabbits (106).The antioxidant and
antihyperlipidemic activities of the extracts of leaves
and calyces of Hibiscus sabdariffa were investigated
by studying in vitro inhibitory activity on lipid
peroxidation and in vivo effects on cholesterol
induced hyperlipidemia. Highest antioxidant activity
was exhibited by ethanolic extract of calyces
followed by ethanolic extract of leaves followed by
aqueous extract of leaves of Hibiscus sabdariffa. In
cholesterol induced hyperlipidemic model, the
groups of rats treated with extracts of calyces and
leaves of Hibiscus sabdariffa showed a significant
decrease in the serum TC, LDL-C, VLDL-C, TAG
values along with an increase in serum HDL-C
levels. The treated groups also showed significant
decrease in the atherogenic index, LDL-C: HDL-C
risk ratios, and in the levels of SGOT, SGPT and ALP
activities compared to cholesterol induced
hyperlipidemic control group(107). The effects of
aqueous extract of Hibiscus sabdariffa (Hs) on body
weight gain and its protective effects on the liver by
improving lipid metabolism were studied in high fat
diet-induced obese C57BL/6NHsd mice. Oral
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administration of the Hs extract reduced fat tissue
accumulation, diminished body weight gain and
normalized the glycemic index as well as reduced
dyslipidemia compared to the obese mice group
that did not receive Hs treatment. Hs treatment also
attenuated liver steatosis, down-regulated SREBP-1c
and PPAR-γ, blocked the increase of IL-1, TNF-α
mRNA and lipoperoxidation and increased catalase
mRNA(108). The effect of a standardized Hibiscus
sabdariffa calyces aqueous extract on body weight
was evaluated in an obese mice model induced by
the administration of monosodium glutamate.
Hibiscus sabdariffa aqueous extract was orally
administered (120 mg/kg/day) for 60 days to
healthy and obese mice. Hibiscus sabdariffa
administration significantly reduced body weight
gain in obese mice and increased liquid intake in
healthy and obese mice. Triglycerides and
cholesterol levels showed non-significant reductions
in animals treated with Hibiscus sabdariffa (109).
Hibiscus sabdariffa water extract (HSE) treatment
reduced fat accumulation in the livers of hamsters
fed with fat diet (HFD) in a concentration-dependent
manner. Administration of HSE reduced the levels of
liver cholesterol and triglycerides, which were
elevated by HFD. Analysis of the effect of HSE on
paraoxonase 1, an antioxidant liver enzyme,
revealed that HSE potentially regulated lipid
peroxides and protected organs from oxidation-
associated damage. The markers of liver damage
such as serum alanine aminotransferase and
aspartate aminotransferase levels that were elevated
by HFD were also reduced by HSE treatment. The
effects of HSE were as effective as treatment with
anthocyanin; which indicated that anthocyanins
present in the HSE may play a crucial role in the
protection established against HFD-induced
obesity(110-111).The effect of Hibiscus sabdariffa
(Hs) calyx extract on fat absorption-excretion and
body weight was studied in rats. Rats were fed with
either a basal diet (SDC = Control diet) or the same
diet supplemented with Hs extracts at 5%, 10% and
15% (SD5, SD10 and SD15). Only SD5 did not
show significant increases in weight, food
consumption and efficiency compared to SDC. The
opposite occurred in SD15 group which showed a
significant decrease for these parameters. The
SD10 responses were similar to SD15, with the
exception of food consumption. In both SDC and
SD5 groups, no body weight loss was observed;
however, only in the latter group there was a
significantly greater amount of fatty acids found in
feces(112).Hibiscus sabdariffa polyphenols (HPE)
exhibited more potency to decrease plasma
cholesterol and LDL cholesterol than the
crude extract HSE, and increased HDL cholesterol
dose-dependently. It decreased the lipid content of
hepatocyte through the activation of AMPK and
reduction of SREBP-1, thus inhibiting the expression
of fatty acid synthase and HMG-CoA reductase.
LDLR and LDL binding of HepG2 cells were
enhanced when treated with HPE(113). The effects
of Hibiscus sabdariffa on adipogenic differentiation
of 3T3-L1 cells were studied at the cellular and
molecular levels. Hibiscus extract inhibited the
adipocyte differentiation of 3T3-L1 preadipocytes
induced by insulin, dexamethasone, and
isobutylmethylxanthine (IBMX) in a dose-dependent
manner. Hibiscus blocked the cytoplasmic lipid
accumulation when administered at the onset of
differentiation and 4 days after induction of
differentiation. The inhibitory effect of hibiscus on
adipogenic lipid accumulation of preadipocytes was
significant (P<0.01) between control cells and cells
treated with hibiscus(114). Hibiscus sabdariffa
extract inhibited the adipocyte differentiation
through the modulation of PI3-K/Akt and ERK
pathway that play pivotal roles during
adipogenesis(115).The cholesterol-lowering
potential of Hibiscus sabdariffa extract (HSE) was
investigated in human subjects, a clinical study was
conducted using an oral preparation of HSE
capsules. The study consisted of 42 volunteers with
a cholesterol level of 175 to 327 mg/dl. They were
randomly divided into 3 groups: group I (1 capsule
of HSE during each meal), group II (2 capsules),
and group III (3 capsules). HSE caused significant
decrease in serum cholesterol level in subjects from
groups I and II after 4 weeks. HSE after 2 weeks,
decreased serum cholesterol levels in all groups
(P<0.05 for groups I-III) compared with baseline
values by 7.8% to 8.2%, while, a reduction in serum
cholesterol level by 8.3% to 14.4%, was recorded
after 4 weeks. The serum cholesterol level for 71%
of group II volunteers was significantly lowered with
a mean reduction of 12% (P<0 .05)(116). In a
sequential randomized controlled clinical trial, 60
patients with diabetes were randomly assigned into
two groups: sour tea (Hibiscus sabdariffa, ST) and
black tea (BT). They were instructed to consume sour
tea or black tea two times a day for 1 month to
investigate the hypolipidemic effects of sour tea in
patients with diabetes and compare them with black
tea. In the Hibiscus sabdariffa group, the mean of
high-density lipoprotein-cholesterol (HDLc)
increased significantly (P=0.002) at the end of
the study, whereas changes in apolipoprotein-A1,
and lipoprotein (a) were not significant. Also, a
significant decrease in the mean of total cholesterol,
low density lipoprotein-cholesterol, triglycerides, and
Apo-B100 were seen in this group. In the BT group,
only HDLc showed significant change (P=0.002)
at the end of the study, while, the changes in the
other measures were not statistically
significant(117).A triple blind randomized placebo-
controlled clinical trial was carried out to determine
the effects of Hibiscus sabdariffa (HS) calices on
controlling dyslipidemia in 72 obese adolescents.
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They received 2 grams of fine powdered calices of
Hibiscus sabdariffa per day for one month, while
controls received placebo powder with the same
dietary and physical activity recommendations and
duration of exposure. Full lipid profile and fasting
blood sugar were measured before and after the
trial. In the Hibiscus sabdariffa calyces treated
group, serum total cholesterol, low density
lipoprotein cholesterol and serum triglyceride
showed a significant decrease but high density
lipoprotein cholesterol level was not changed
significantly(118).A clinical trial was carried out to
confirm the metabolic-regulating and liver-
protecting effect of Hibiscus sabdariffa extracts
(HSE). Subjects with a BMI 27 and aged 18–65,
were randomly divided into control and HSE-treated
groups, for 12 weeks. the results revealed that
consumption of HSE reduced body weight, BMI,
body fat and the waist-to-hip ratio. Serum free fatty
acids were also lowered by HSE. Anatomic changes
revealed that HSE improved the illness of liver
steatosis. Ingestion of HSE was well tolerated and
there was no adverse effect during the trial(119). A
total daily dose of 100 mg of Hibiscus sabdariffa
extract powder (HSEP) was orally administered in
capsules for one month to determine its effect on
lipid profiles of individuals with dyslipidemia
associated with metabolic syndrome (MeSy). The
MeSy patients treated with HSEP had significantly
reduced glucose and total cholesterol levels,
increased HDL-c levels, and an improved TAG/HDL-
c ratio, a marker of insulin resistance (P<0.05).
Furthermore, a triglyceride-lowering effect was
observed in MeSy patients treated with HSEP plus
diet, and in individuals without MeSy treated with
HSEP. Significant differences in total cholesterol,
HDL-c, and the TAG/HDL-c ratio were found when
the means of absolute differences among treatments
were compared (P<0.02)(120). In a double blind,
placebo controlled, randomized trial, sixty subjects
with serum LDL values in the range of 130-190
mg/dl and with no history of coronary heart disease
were randomized into experimental and placebo
groups. The experimental group received 1 gm of
the extract for 90 days, while the placebo received
a similar amount of maltodextrin in addition to
dietary and physical activity advice for the control of
their blood lipids. Body weight, serum LDL
cholesterol and triglyceride levels decreased in both
groups, there were no significant differences
between the experimental and placebo group. At a
dose of 1 gm/day, Hibiscus sabdariffa
leaf extract did not appear to have a blood lipid
lowering effect(121).
Antidiabetic effects
The inhibitory effect of aqueous extracts of two
varieties (red and white) of Hibiscus sabdariffa
calyces on carbohydrate hydrolyzing enzymes (α-
amylase and α-glucosidase) was studied as a
possible mechanism for their antidiabetes
properties. The extracts caused inhibition of α-
amylase and α-glucosidase activities in vitro. The
IC50 revealed that the red variety (25.2 μg/ml)
exhibited higher α-glucosidase inhibitory activity
than the white variety (47.4 μg/ml), while the white
variety (90.5 μg/ml) exhibited higher α-amylase
inhibitory activity than the red variety (187.9μg/ml).
However, the α-glucosidase inhibitory activities of
both calyces were higher than that of their α-
amylase inhibitory activities (122). The antidiabetic
and antioxidant effects of purple roselle extract
were studied in streptozotocin(STZ)- induced
diabetes in rats. After 21 days treatment, roselle
extract lowered blood sugar (both curative and
preventive), increased of antioxidant capacity, and
improved insulin production (123).The effects of
Hibiscus sabdariffa UKMR-2 (HSE) variety (100
mg/kg/bw orally for 28 consecutive days) on fertility
of streptozotocin-induced diabetic was studied in
rats. Administration of HSE significantly lowered the
level of fasting blood glucose and increased plasma
insulin level. Sperm quality was improved with
significantly higher sperm concentrations (P<0.05)
and sperm motility (P<0.001) as well as lower
percentage of sperm abnormality (P<0.05) as
compared to the diabetic group. Plasma follicle-
stimulating hormone (FSH) level was significantly
elevated (P<0.05) in HSE group than in diabetic
group while no significant alteration in plasma
testosterone and luteinizing hormone (LH) level were
seen between groups(124). The effect of oral
administration of aqueous extract of Hibiscus
sabdariffa (HS, at a 12 hr interval, daily for 7, 14
and 21 days, respectively) was evaluated on blood
glucose, serum sodium and serum potassium
concentrations in albino rats. The results revealed a
significant decrease (P<0.05) in blood glucose level
after 21 days of administration of HS and a
significant decrease (P<0.05) in serum sodium
concentration at 7 and 14 days of
administration(125).The mechanism underlying the
antidiabetic effect of ethanolic extract of Hibiscus
sabdariffa calyxes (HS-EE, 0.1 and 1.0 g/kg/day,
respectively, for 6 weeks) was investigated in
streptozotocin-induced diabetic rats. HS-EE 1.0
g/kg/day significantly decreased the blood glucose
level by 38 ± 12% in diabetic rats but not in normal
rats. In normal rats, treatment with 1.0 g/kg HS-EE
increased the basal insulin level significantly as
compared with control normal rats (1.28 ± 0.25
and 0.55 ± 0.05 ng/ml, respectively). Diabetic rats
treated with 1.0 g/kg HS-EE also showed a
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significant increase in basal insulin level as
compared with the control diabetic rats (0.30 ±
0.05 and 0.15 ± 0.01 ng/ml, respectively).
Microscopic histological examination showed that
HS-EE 1.0 g/kg significantly increased the number
of islets of Langerhans in both normal rats (1.2 ±
0.1 and 2.0 ± 0.1 islet number/10 low-power fields
(LPF) for control and HS-EE treated group,
respectively) and diabetic rats (1.0 ± 0.3 and 3.9 ±
0.6 islet number/10 LPF for control and HS-EE
treated group, respectively)(126).The effect of
Hibiscus sabdariffa polyphenol extract (HPE) was
investigated in streptozotocin (STZ) induced diabetic
nephropathy. The results revealed that HPE reduced
kidney mass induced by STZ significantly, as well as
improving hydropic change of renal proximal
convoluted tubules in the rats. HPE also significantly
reduced serum triglyceride, total cholesterol and LDL
in STZ induced rats. Treatment with HPE significantly
increased the activity of catalase and glutathione
and reduced lipid peroxidation (thiobarbituric acid-
reactive substances)(127). The protective effect of
Hibiscus sabdariffa polyphenolic extract (HPE) was
investigatedin in type 2 diabetic rat model.
Treatment with HPE reduced hyperglycemia,
especially at the dose of 200 mg/kg. HPE decreased
serum triacylglycerol, cholesterol, and the ratio of
low density lipoprotein/high density lipoprotein
(LDL/HDL). Diabetes promoted plasma advanced
glycation end product (AGE) formation and lipid
peroxidation, while HPE significantly reduced these
elevations. Immunohistological observation revealed
that HPE inhibited the expression of connective tissue
growth factor (CTGF) and receptor of AGE (RAGE),
which was increased in type 2 diabetic aortic
regions. HPE also recovered the weight loss found in
type 2 diabetic rats(128). The possible protective
effects of Hibiscus sabdariffa calyxes
aqueous extract (HSL,100mg/kg/day, orally for 28
consecutive days), as an antidiabetic and
antioxidant agent against oxidative liver injury in
streptozotocin-induced diabetic were investigated in
rats. Supplementation of HSL significantly lowered
the level of fasting blood glucose and increased
plasma insulin level compared to negative control
(P<0.05). Alanine aminotransaminases and
aspartate aminotransferase level were found to be
significantly reduced in the treated group compared
with negative control(129). The antidiabetic,
hypolipidimic, antioxidant and histopathological
effects of hydroalcoholic extract of flower Hibiscus
rosa-sinensis (HEFHR) were studied in alloxan
induced diabetes in rats. HEFHR possessed
significant and sustained oral antidiabetic activity,
comparable with the hypoglycemic effect of
glibenclamide and sulphonylurea. Flower extract of
HRS was more efficacious in lipid lowering effect
and in antioxidative activity than glibenclamide.
After 28 day treatment with flower extract, size of
islets was significantly increased and necrosis and
atrophy of islets were significantly improved(130).
The effects of Hibiscus sabdariffa (HSE) on diabetic
nephropathy was tested in streptozotocin induced
type 1 diabetic rats. HSE was capable of reducing
lipid peroxidation, increasing catalase and
glutathione activities significantly in diabetic kidney,
and decreasing the plasma levels of triglyceride,
low-density lipoprotein and increasing high-density
lipoprotein value. In histological examination, HSE
improved hyperglycemia-caused osmotic diuresis in
renal proximal convoluted tubules in diabetic rats.
The results also showed that it up-regulated
Akt/Bad/14-3-3γand NF-κB-mediated
transcription. Accordingly, HSE ameliorated
diabetic nephropathy via improving oxidative status
and regulating Akt/Bad/14-3-3γsignaling(131).
Antioxidant effect
In studying the antioxidant effect of aqueous
extracts of two varieties (red and white) Hibiscus
sabdariffa calyces, the red variety possessed higher
antioxidant capacity as exemplified by the •OH
scavenging abilities, Fe2+ chelating ability, and
inhibition of Fe2+-induced pancreatic lipid
peroxidation in vitro(122). The antioxidant activity of
the dried petal extracts of Hibiscus sabdariffa was
investigated using the DPPH scavenging assay. The
IC50 values of the roselle extract was 0.24 mg/ml
while that of ascorbic acid was 0.35 mg/ml(26). The
antioxidant activity was performed using wistar rats.
The treatments were administered via oral route and
at single dose for seven days, followed by injection
of doxorubicin. The calyx extract of Hibiscus
sabdariffa had attenuated the side effect of
doxorubicin (P<0.05) regarding the markers of
oxidative stress(36). Hibiscus sabdariffa leaves
extracts showed good antioxidant activity as all the
three extracts ( aqueous, ethanol and ethyl acetate)
exhibited good DPPH radial scavenging activity with
IC50 values ranging from 46.13 ± 0.37 to 94.16 ±
0.56 μg/ml(30,65).The calyx extracts of Hibiscus
sabdariffa from Ankara- Turkey showed that the
total phenol contents of the extracts were between
16.4-49.1 mg gallic acid/g extract. They showed
strong antioxidant effects, however, the inhibitory
effects of the extracts in DPPH radical scavenging
assay, were not dose dependent. On the other hand
there was no correlation between the phenol content
and radical scavenging activities of the
extracts(132).The in vitro antioxidant activities of
Hibiscus sabdariffa leaves extract were measured by
ABTS radical cation decolorization assay, they
showed strong antioxidant activity(133). The
antioxidant activity of ethanolic seed extract of
Hibiscus sabdariffa (100 and mg/kg HS) was
investigated in toxicity induced by chronic
administration of sodium nitrate (25mg/kg) in wistar
rats. The animals were sacrificed at the end of 60
days and blood samples were taken for analysis of
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total protein and some haematological indices. The
haematological toxicity induced by chronic
administration of sodium nitrate were alleviated by
the antioxidant effect Hibiscus sabdariffa (134).The
polyphenolic content and antioxidant activity of
methanol, ethanol, acetone and water extracts of
Hibiscus sabdariffa calyx were studied using 2,2-
diphenyl-1-picryl hydrazine (DPPH) inhibition and
lipid peroxidation inhibition. Methanol extract gave
the highest inhibition to DPPH (78%) and was only
significantly different (P<0.05) from acetone and
water extracts. Ethanol gave the highest inhibition to
lipid peroxidation (26%) but was not significantly
different (P<0.05) from the other solvent extracts.
There was a stronger correlation obtained between
total phenolic content and inhibition of DPPH (r =
0.969) compared to total flavonoid content and
DPPH (r = 0.742)(135).Hibiscus sabdiriffa showed
antioxidant activity, the roselle extracts blended at
various proportions with fruit (mango, papaya and
guava) juices increased total phenolics (54.6-10.8
mg gallic acid/ 100 g) and antioxidant activity
(1.80-1.37 mmol/l0) (136). The effect of an
aqueous Hibiscus sabdariffa extract (HSE) on the
systemic antioxidant potential (AOP; assayed by
ferric reducing antioxidant power (FRAP)) was
compared with a reference treatment (water) in eight
healthy volunteers. HSE caused significantly higher
plasma areas under the curve (AUC) of FRAP, an
increase in Ae(0-24) of FRAP, ascorbic acid and
hippuric acid, whereas malondialdehyde excretion
was reduced. The increased urinary hippuric acid
excretion after HSE consumption indicated a high
biotransformation of the ingested HSE polyphenols,
most likely caused by the colonic microbiota.
Furthermore, the main hibiscus anthocyanins as well
as one glucuronide conjugate were quantified in the
volunteers' urine (0.02% of the administered
dose)(137).The antioxidant and drug metabolizing
potentials of hibiscus anthocyanin extract was
investigated in CCl4- induced oxidative damage of
rat liver. Hibiscus anthocyanin extract significantly
increased the CCl4-mediated decrease in
antioxidant enzymes (catalase, superoxide
dismutase, glutathione peroxidase, and glutathione
reductase). However, the level of nonenzymic
antioxidant molecules (vitamins C and E) were
significant preserved by hibiscus
anthocyanin extract. There was an induction of
phase II drug-detoxifying enzymes: glutathione S-
transferase, NAD(H): quinone oxidoreductase, and
uridyl diphosphoglucuronosyl transferase by 65, 45,
and 57%, respectively. Accordingly, Hibiscus
sabdariffa anthocyanin extract can act as a
prophylactic drug by intervening as a free radical
scavenger both in vitro and in vivo as well as
inducing the phase II drug detoxification
enzymes(138).
Effects on smooth muscles
Addition of an aqueous extract of Hibiscus
sabdariffa calyces (2.5 ml/bath approximately 125
mg of starting crude material) inhibited the tone of
various isolated muscle preparations (rabbit aortic
strip, rhythmically contracting rat uterus, guinea-pig
tracheal chain and rat diaphragm). Other muscles
were stimulated (quiescent rat uterus and frog rectus
abdominis)(88). The methanol extracts of Hibiscus
sabdariffa showed a significant (P<0.01) dose
dependent relaxant effect (IC50 = 350 μM) on rat
ileal strip comparable to the effect shown by
nifedipin and papaverine as reference compounds.
The extract when administered intraperitoneally, it
also significantly (P<0.05–0.01) reduced the
intestinal transit (13-35%) in rats (IC50 = 250
μM)(28). The aqueous extract of Hibiscus sabdariffa
calyces extracts induced rat bladder and uterine
contractility in a dose-dependent manner via a
mechanism unrelated to local or remote autonomic
receptors or calcium channels(139). The Vascular
effects of crude extract of dried and powdered
calyces of Hibiscus sabdariffa were evaluated on
isolated thoracic aorta of male Wistar rats. The
Hibiscus sabdariffa crude extract induced
endothelium-dependent relaxant effects. The
endothelium-dependent relaxations were resulted
from NOS activation(80).
Gastrointestinal effects
The gastro-protective potential of Hibiscus
sabdariffa against indomethacin-induced gastric
ulcer was evaluated in the rat. 70% alcoholic
extracts of Hibiscus sabdariffa (100, 400, 800
mg/kg) were gavaged to rats for 4 consecutive days.
Gastric ulcers were induced by the one time gavage
of indomethacin (30mg/kg). The animals were killed
6 h after the indomethacin administration. Ulcer
index was significantly and dose- dependently
decreased in rat treated with Hibiscus
sabdariffa(140).The anti-ulcerogenic property of
ethanolic extract of dried calyces of Hibiscus
sabdariffa in different ulcer models was studied in
Wistar albino rats. The extract at adose of 250 and
500 mg/kg bw, orally showed a significant effect in
cold restraint stress, pylorus ligation, necrotizing
agents (80% ethanol, 0.2 M NaOH and 25% NaCl)
and indomethacin-induced gastric ulcer models. The
extract was also significantly decreased the basal
gastric acid secretion, significantly increased gastric
wall mucus secretion and non-protein sulfhydryl
concentrations in gastric tissue and significantly
reduced the ethanol-induced elevated levels of
malondialdehyde in the rat stomach(141). The
antidiarrheal effect of the ethanolic calyx extract of
Hibiscus sabdariffa was studied using castor oil-
induced diarrheal model mice.
The extract demonstrated a significant antidiarrheal
activity against castor oil-induced diarrheal in mice,
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it decreased the frequency of defecation and
increased the mean latent period at the doses of
250 and 500 mg/kg bw (P<0.01)(142).The effects
of aqueous extracts of the calyces of Hibiscus
sabdariffa on intestinal transit was studied in
experimental rats. The dried calyces of Hibiscus
sabdariffa was pulverized and 10% extracts of
powder were administered orally to rats at varying
doses (0.5/100g, 1ml/100g, 2ml/100g bw). After
30 minutes, each animal was then given 1.5 ml of a
dye solution orally. One hour after administering the
dye, each rat was sacrificed and the intestine
carefully dissected out. The length of the intestine
and the transit point of the orally administered dye
were then measured. The transit point was
calculated as a percentage of the total length of the
intestine. Hibiscus sabdariffa caused significant
reduction in the transit points of the dye(143).
Effect on urinary system
The diuretic activity of Hibiscus sabdariffa aqueous
extract was evaluated on in vivo and in situ models.
The aqueous extract was administrated in increasing
doses and the diuresis produced and disposal of
electrolytes were evaluated. The renal filtration rate
with plant extract, furosemide and amiloride were
evaluated in isolated kidney. The diuretic and
natriuretic effect of Hibiscus sabdariffa aqueous
extract showed a dose-dependent behavior. The
pharmacological constants of natriuretic effect was
ED50 = 86 mg/kg and Emax = 0.9 mEq/100 g/5
h. In the in vitro model, renal filtration was
increased 48% with the aqueous extract of Hibiscus
sabdariffa and an additive effect was recorded
when Hibiscus sabdariffa aqueous extract was
perfused with furosemide (144). The diuretic,
natriuretic, and potassium sparing effects of Hibiscus
sabdariffa were due in part to the modulation of
aldosterone activity by the presence of compounds
potentially responsible for this modulation, as
anthocyanins, flavonoids, and chlorogenic
acid(102).Supplementation of aqueous extract of
Hibiscus sabdariffa at different doses (250, 500 and
750 mg/kg bw) significantly lowered the deposition
of stone-forming constituents in the kidneys and
serum of urolithiatic rats. These findings were
confirmed by the histological investigations(145).
The possible beneficial effects of aqueous extracts
of Hibiscus sabdariffa calyces and anthocyanins
were evaluated in an adenine-induced chronic
kidney disease (CKD) model. Rats were orally
treated, for 28 consecutive days, either adenine
alone or together with either aqueous extract of
Hibiscus sabdariffa calyces (5 and 10%) or
anthocyanins (50, 100 and 200 mg/kg of
anthocyanin concentrate) and for comparative
purposes, two groups of rats were given lisinopril
(10 mg/kg). When either Hibiscus sabdariffa
aqueous extract or the anthocyanins isolated from it
was administered along with adenine, the adverse
effects of adenine-induced CKD were significantly
lessened, in a dose-dependent manner. The effects
were similar to those obtained by administration of
lisinopril(146).
Antiinflammatory, analgesic and antipyretic
effects
The essential oil of Hibiscus sabdariffa exhibited
excellent anti-inflammatory activity in
lipopolysaccharide (LPS)-stimulated macrophage
RAW 264.7 cells. The nitric oxide (NO) inhibition
rate reached 67.46% when the concentration of the
essential oil was 200 μg/ml. Further analysis
showed that the anti-inflammatory activity of the
essential oil extracted from Hibiscus sabdariffa
might be exerted through inhibiting the activation of
NF-κB and MAPK (JNK and ERK1/2) signaling
pathways to decrease NO and pro-inflammatory
cytokine (IL-1, IL-6, TNF-α, COX-2, and iNOS)
production(147). The antiinflammatory effect of
seed of Hibiscus sabdariffa was tested in rats. The
oral administration of petroleum ether extract of
Hibiscus sabdariffa seeds reduced the paw edema
significantly that was induced by carrageenan in
dose dependent manner. After 3 h of the treatment
at 4 and 8 ml/kg bw, paw edema was reduced by
27.9% (P<0.05) and 34.2% (P<0.01), respectively.
In contrast, the ethanolic extract of Hibiscus
sabdariffa seeds did not show significant reduction
in paw edema (inhibition 0%) even at the maximum
dose (400 mg/kg bw). In vascular permeability test,
oral administration of diclofenac sodium at 10
mg/kg bw, and petroleum ether extract of Hibiscus
sabdariffa seeds (at 4 and 8 mg/kg bw) significantly
(P<0.01) inhibited the dye leakage induced by
acetic acid as compared to control. In cotton pellet
induced granuloma test, granuloma formation was
inhibited significantly after administration of
petroleum ether extract of Hibiscus sabdariffa seeds
for 6 consecutive days as compared to control
group. The test dose (4 and 8 ml/kg bw) showed
30.3% and 27.2% of inhibition (P<0.01) respectively
as compared to the control group. The peripheral
analgesic activity of petroleum ether extract was
measured by acetic acid induced writhing test.
Hibiscus sabdariffa seed petroleum ether extract
exhibited a significant level of inhibition in
abdominal writhes produced by acetic acid
especially with high dose (8 ml/kg bw, 45.0%,
P<0.001) compared to control group(44).The anti-
inflammatory activity of methanolic leaves extract of
Hibiscus sabdariffa (250 and 500 mg/kg bw) was
investigated in adult Wistar rat using carrageenan
model. There was significant reduction (P<0.05) in
paw diameter in the group received high dose (500
mg/kg bw) of methanolic extract of Hibiscus
sabdariffa from 0.566±0.023 to 0.414±0.009 as
compared with the untreated group(18). The effects
of the extracts from Hibiscus sabdariffa calyces on
nociceptive response were studied using writhing,
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hot plate and formalin test in mice, the antipyretic
activity in yeast-induced fever in rats and anti-
inflammatory activity on carrageenin-induced paw
edema in rats. Oral administration of the ethanol
extract at the dose of 800 mg/kg significantly
decreased the number of contortions and stretchings
induced by acetic acid in mice. Neither the ethanol
nor aqueous extract had an effect in the formalin
and hot plate tests in mice. The ethanol and the
vacuum dried extract of Hibiscus sabdariffa calyces
(200-800 mg/kg, po) decreased the yeast-induced
fever in rats, while, Hibiscus sabdariffa extract had
no effect on carrageenin induced paw edema in
rats(148). The antinociceptive and anti-
inflammatory of the ethanolic calyx extract of
Hibiscus sabdariffa were studied in mice. The
antinociceptive activity of the extract was evaluated
by using the acetic acid-induced writhing test. The
anti-inflammatory effect of the extract was tested by
using the xylene-induced ear edema model in mice.
In acetic acid-induced writhing test, the extract
inhibited writhing in mice significantly compared
with control (P<0.01). The extract showed significant
inhibition of ear edema formation in xylene-induced
ear edema model in mice in a dose-related manner
compared with control (P<0.01)(142). The aqueous
extracts of Hibiscus sabdariffa were tested for anti-
inflammatory, analgesic and antipyretic activities in
animal models. The extract had no effect on paw
edema but had an inhibitory effect on yeast induced
pyrexia and showed significant effect on the hot
plate reaction time(149).
Immunological effects
The immunomodulatory activity of the total crude
leaf extract of Hibiscus sabdariffa (125, 250 and
500 mg/Kg bw, daily for 14 days) was studied in
Wistar albino rats. All the doses caused an increase
in mean red blood cell counts as compared to
control group. The mean percentage of neutrophils,
monocytes, basophils and eosinophils was
increased with dose, while the opposite was true for
percentage of lymphocytes. The mean
hemagglutination antibody (HA) titers for the herb
were higher than control though no statistical
difference (P≥0.05) was observed. Similar effects
were observed with neutrophil adhesions response
as that of HA titers. For delayed-type
hypersensitivity (DTH), the highest footpad thickness
(175.2% increment) was observed at a dose of 500
mg/Kg bw, after 12 h and was statistically
significant (P≤0.05) as compared to control(23).
The immunomodulatory properties of two fractions
of the aqueous alcoholic extract of the dried calyx
of Hibiscus sabdariffa were studied in experimental
animals. Immunomodulatory activity was evaluated
using red blood cell-induced immunostimulation.
The ethyl acetate soluble fraction (EAC) exhibited a
significant dose-dependent immunostimulation
(P<0.05), higher than that observed for levamisole
(positive control). The residual water-soluble fraction
exhibited immunostimulatory activity at 100 mg/kg
bw. The two fractions caused a significant reduction
in production of tissue necrosis factor-alpha and an
increase in interleukin 10(150).The
immunomodulatory activity of water and alcohol
extracts (including its fractions) of the dried calyx of
Hibiscus sabdariffa was evaluated in mice. The
ability of the extracts to inhibit or enhance the
production of two cytokines, [tumor necrosis factor-
alpha (TNF- alpha) and interleukin-10 (IL-10)],
implicated as proinflammatory and
antiinflammatory interleukins were also evaluated.
The extracts at doses of 50 mg/kg were found to
possess higher immunostimulatory activities in
comparison with levamisole (positive control), with
significant effects when compared with the vehicle-
treated group (P<0.01). Increased activity was
observed with increase in doses of the 50% ethanol
and absolute ethanol extracts. The insoluble fraction
exhibited a significant dose-dependent
immunostimulatory activity (P<0.05), while the
residual water-soluble fraction exhibited activity at
100 mg/kg bw(151). The aqueous extract of
Hibiscus sabdariffa promoted the production of IL-6
and IL-8 and decreases the concentration of MCP-1
in a dose-dependent manner. This effect was not
due to a concomitant increase in the antioxidant
capacity of plasma. The mechanisms involved a
direct inhibition of inflammatory and/or metabolic
pathways responsible for MCP-1 production, and
may be relevant in inflammatory and chronic
conditions in which the role of MCP-1 was well
established(152).
Effect on reproductive systems
The sub-chronic effect of Hibiscus sabdariffa (HS)
calyx aqueous extract (1.15, 2.3, and 4.6 g/kg for
12-weeks ) on testis was investigated in rats. Three
test groups received different doses of 1.15, 2.30,
and 4.60 g/kg based on the LD50. Results did not
show any significant (P>0.05) change in the
absolute and relative testicular weights, but there
was a significant (P<0.05) decrease in the
epididymal sperm counts in the 4.6 g/kg group,
compared to the control. The 1.15 g/kg dose group
showed distortion of tubules and a disruption of
normal epithelial organization, while the 2.3 g/kg
dose showed hyperplasia of testis with thickening of
the basement membrane and 4.6 g/kg dose group,
showed disintegration of sperm cells(153).
The potential adverse effects of the cold and hot
Hibiscus sabdariffa calyx extracts (200 mg/kg bw,
for 4 weeks, orally) on sperm morphology and
testicular ultrastructure were studied in albino mice.
The results revealed that aqueous extracts of dried
calyx of Hibiscus sabdariffa, either cold or boiled,
altered normal sperm morphology and testicular
ultrastructure and adversely influenced the male
reproductive fertility in albino mice(154). The effects
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of Hibiscus sabdariffa (HS) on the development of
the male reproductive tract following in utero
exposure were investigated in rats. Pregnant rats
received 250 or 500mg/kg of HS extract from
gestational day 12 until day 21 of lactation. Both
doses of HS increased the body weight of male
offspring at weaning, without compromising the
puberty onset parameters. At puberty, there was a
significant increase in the vas deferens absolute
weight and a significant reduction in the relative
weight of kidney at higher dose. At adulthood, the
highest dose significantly reduced the sperm
production in relation to controls and both doses
provoked a reduction in the relative sperm number
in the epididymis without affecting the sperm
morphology(155).The effects of different
concentrations of aqueous extracts of Hibiscus
sabdariffa calyces (10%, 15% and 20%) in drinking
water for 10 consecutive weeks, and its
anthocyanins (50, 100, 200 mg/kg for 5 days,
orally) were investigated in male and female rats,
on the weight and histology of the testis, and on
some biochemical constituents in testicular
homogenates, as well as on plasma concentrations
of testosterone, luteinizing hormone and estradiol.
The possible presence of an estrogenic effect of
the extract and anthocyanins on the uteri of
immature female rats was also tested. Neither the
Hibiscus sabdariffa extract nor the anthocyanins
significantly altered either testicular weight and
histology, or uterus weight. Plasma concentrations of
the three hormones, the testicular concentrations of
protein, reduced glutathione and total cholesterol,
and superoxide dismutase activity were all
insignificantly affected by either the extract or the
anthocyanins(156). Hibiscus sabdariffa consumption
caused delayed puberty of the offspring either the
mothers consumed it during pregnancy or during
lactation periods(157-159).Furthermore,
consumption of aqueous extract of HS during the
juvenile-pubertal period decreased fluid and food
consumption, increased weight gain and delayed
puberty onset in rats(160).
Protective effects
The effects of the water extract of the dried flowers
of Hibiscus sabdariffa and Hibiscus anthocyanins
(HAs) were evaluated in paracetamol-induced
hepatotoxicity in rats. The water extract was given in
drinking water for 2, 3 or 4 consecutive weeks, and
the HAs were given orally at doses of 50, 100 and
200 mg/Kg for five consecutive days. The extract
for 4 weeks (but not for 2 or 3 weeks) significantly
improved some of the liver function tests, but did not
alter the histology of the paracetamol-treated rats.
At a dose of 200 mg/Kg, the hepatic histology and
the biochemical indices of liver damage were
restored to normal(161). Dried flower Hibiscus
sabdariffa (HSE) extracts (1-5% for 9weeks) were
tested for hepatoprotective effects against liver
fibrosis induced by carbon tetrachloride (CCl4) in
rats. HSE significantly reduced the liver damage
including steatosis and fibrosis in a dose dependent
manner. HSE also significantly decreased the
elevation in plasma aspartate aminotransferase
(AST) and alanine aminotransferase (ALT) and
restored the decrease in glutathione content and
inhibited the formation of lipid peroxidative products
during CCl4 treatment(162). Pretreatment of rats
with aqueous extract of Hibiscus sabdariffa resulted
in significantly less hepatotoxicity than with Cd alone
as measured by plasma ALT and liver ALT and AST
activities. The extract also protected the rats against
Cd-induced liver, prostate, and testis
lipoperoxidation as evidenced by significantly
reduced MDA values in these organs, as well as
reduced prostatic acid phosphatase activity in the
prostate, when compared to the Cd-only exposed
rats(163).The hepatoprotective effect of the
anthocyanin-rich extract of Hibiscus sabdariffa
calyces (HSARE, 100mg/kg/d for 4 weeks) was
studied in thioacetamide (TAA)-induced
hepatotoxicity in rats. Compared to the TAA-
intoxicated group, HSARE significantly reduced the
serum levels of alanine aminotransferase, aspartate
aminotransferase and hepatic malondialdehyde by
37.96, 42.74 and 45.31%, respectively. It also
decreased hepatic inflammatory markers, including
tumour necrosis factor alpha, interleukin-6 and
interferon gamma (INF-γ), by 85.39, 14.96 and
70.87%, respectively. In addition, it decreased the
immunopositivity of nuclear factor kappa-B and
CYP2E1 in liver tissue, with an increase in the
effector apoptotic marker (caspase-3 positive cells),
restoration of the altered hepatic architecture and
increases in the activities of superoxide dismutase
and glutathione by 150.08 and 89.23%,
respectively(164).The effect of Hibiscus sabdariffa
extract (HSE) on acetaminophen (AAP)-induced liver
injury was investigated in mice. Mice were fed orally
with 200, 400 or 600 mg/kg HSE for 2 weeks and
then injected with 1000 mg/kg AAP. Pretreatment
with HSE decreased lipid peroxidation and
increased catalase activity and glutathione level. It
also decreased AAP-induced liver injury,
accompanied by decreased expression of pJNK, Bax
and tBid in the liver(165). The possible protective
mechanism of the polyphenol extract of Hibiscus
sabdariffa (HPE) against acetaminophen (AAP)-
caused liver damage was studied in mice. Mice were
orally fed with HPE (100, 200 or 300 mg/kg) for
two weeks prior to an ip injection of 1000 mg/kg of
AAP. The pretreating with HPE increased the level of
glutathione (GSH), decreased the level of lipid
peroxidation, and increased catalase activity in the
liver. Histopathological evaluation showed that HPE
decreased AAP-induced liver sterosis accompanied
by a decreased expression of AIF, Bax, Bid, and p-
JNK in the liver. An in vitro assay revealed that HPE
Ali et al / Pharmacological and therapeutic importance of Hibiscus sabdariffa- A review
466|International Journal of Pharmaceutical Research | Apr-june 2018 | Vol 10 | Issue 3
reduced AAP-induced death of BABL/c normal liver
cells (BNLs), reversed the lost mitochondrial potency
and improved the antioxidative status(166). CCl4 in
rats elevated aspartate aminotransferase, alanine
transaminase, alkaline phosphatase, total protein,
globulin levels significantly (P<0.05) while albumin
was reduced. CCl4 significantly reduced sperm
count, viability and motility (P<0.05), while sperm
head abnormality increased. However,
administering of Hibiscus sabdariffa extract at the
doses of 300 and 600 mg/kg caused the reversal of
these effects significantly(167).The protective effect
of extract of Hibiscus sabdariffa was studied against
SGD-induced PC12 cells injury. Cells were
pretreated with different concentrations of Hibiscus
sabdariffa extract (HSE) for 2 hr, and then exposed
to SGD condition for 6, 12 and 18 hr. SGD caused
a major reduction in cell viability after 6, 12, and 18
hr as compared with control cells (P<0.001).
Pretreatment with HSE (30-500 g/ml) significantly
increased cell viability following SGD insult for 6, 12
and 18 hr. A significant increase in cell apoptosis
was seen in cells under SGD condition after 12hr as
compared with control cells (P<0.001). Pretreatment
with HSE significantly decreased cell apoptosis
subsequent SGD condition after
12hr(168).Flavonoid-rich aqueous fraction of
methanolic extract of Hibiscus sabdariffa calyx was
evaluated for anti-hepatotoxic activities in
streptozotocin-induced diabetic wistar rats. The
ameliorative effects of the extract on STZ-diabetes
induced liver damage was evident from the
histopathological analysis and the biochemical
parameters evaluated in the serum and liver
homogenates. Reduced levels of glutathione,
catalase, superoxide dismutase and glutathione
peroxidase in the liver of diabetic rats were restored
to a near normal level in the Hibiscus sabdariffa -
treated rats. Elevated levels of aspartate amino
transferase, alanine amino transferase and alkaline
phosphatase in the serum of diabetic rats were also
restored in Hibiscus sabdariffa -treated rats.
Histologically, hepatic fibrosis and excessive
glycogen deposition in the diabetic rats were
ameliorated in the extract-treated rats(169).The
ameliorative effect of co-administration of aqueous
extract of Hibiscus sabdariffa (HS) and vitamin E
was evaluated on sub-chronic carbamazepine
(CBZ)-induced alterations in semen characteristics in
rats. The result showed that mean sperm counts in
the CBZ-treated alone group was lower than in
groups with HS, Vitamin E, and HS and vitamin E
(P<0.05) when compared to the control groups.
There was significant decrease in mean progressive
sperm motility with an increase in the means non-
progressive motility and non-motile sperm cells of
the CBZ-treated group as compare to the control
group (P<0.05). While there were significant
increases in mean progressive sperm motility with a
decrease in non-progressive motility and non-motile
sperm cell of the groups treated with CBZ in
combination with HS, vitamin E, and HS and vitamin
E, when compared to the CBZ-treated alone and
control groups (P<0.05). There was no considerable
statistically significant different in abnormal sperm
cells in the treatment groups(170).The antigenotoxic
property of Hibiscus sabdariffa dry calyx extracts
was investigated in mice. The dried calyx extracts of
Hibiscus sabdariffa were administered to male
albino mice at doses of 50, 100, and 150 mg/kg
bw, for 7 days followed by a single dose of
interperitoneal injection of sodium arsenite (2.5
mg/kg bw). The calyx extract inhibited the DNA
damage induced by sodium arsenite in a dose
dependent manner(171).
CNS effects
The neuropharmacological effects of the aqueous
extract of Hibiscus sabdariffa (HS) calyx were studied
in rodents. HS (100, 200 and 400 mg/kg, ip)
caused a remarkable dose-dependent decrease in
spontaneous motor activity in mice and increased
the duration of pentobarbital (40 mg/kg, ip)
induced sleep in rats. The extract (100-400 mg/kg,
ip) significantly reduced the exploratory behaviour in
mice. The extract significantly inhibited the intensity
of apomorphine (1 mg/kg, sc) induced stereotypic
behaviour and attenuated climbing in the mice
dose-dependently(172). The nootropic acitivity of
calyces of Hibiscus sabdariffa was studied in mice
using elevated plus maze and passive avoidance
paradigm to evaluate learning and memory
parameters. The aqueous extracts of calyces of
Hibiscus sabdariffa (100 and 200 mg/kg, po)
significantly attenuated amnestic deficits induced by
scopolamine (0.4 mg/kg, ip) and natural aging.
Hibiscus sabdariffa (100 and 200 mg/kg)
decreased the transfer latencies and increased step
down latencies significantly in the aged mice and
scopolamine induced amnesic mice as compared
with piracetam (200 mg/kg, ip).
Acetylcholinesterase activity in the whole brain was
significantly decreased in mice which could be
refere to the underlying mechanism of action(173).
Lactogenic effect
The lactogenic effect of ethanolic seed extract of
Hibiscus sabdariffa was investigated by
administering extract and metoclopramide in albino
rats. The extracts were administered at varying
doses (200, 400, 800 and 1600mg/kg) for six days
orally. The ethanolic seed extract of Hibiscus
sabdariffa possessed lactogenic effect. It caused
significant increase (P<.01) in serum prolactin levels
in a dose dependent manner. The doses of 800 and
1600 mg/kg seemed more effective with serum
prolactin levels of 15.74±0.8 and 17±0.6
respectively, compared to control 6.68 ±0.5
ng/ml(9).
Ali et al / Pharmacological and therapeutic importance of Hibiscus sabdariffa- A review
467|International Journal of Pharmaceutical Research | Apr-june 2018 | Vol 10 | Issue 3
Wound healing effect
The wound healing activities of water in oil cream of
the methanol extract of Hibiscus sabdariffa was
evaluated in rats with superficial skin excision
wounds. Creams containing Hibiscus sabdariffa
extract showed significant (P<0.05) and
concentration dependent wound healing activities.
There was also evidence of synergism with creams
containing a combination of gentamicin and
Hibiscus sabdariffa extract(174).
Side effects and toxicity
The median lethal dose of the calyx extract in rats is
estimated to be higher than 5 g/kg(15). LD50 of
Hibiscus sabdariffa seed extract in albino rats was
also found to be above 5g/kg(9). No acute toxicity
was observed in mice after oral administration of
the ethanol and aqueous extract of Hibiscus
sabdariffa calyces at the dose of 15 g/kg(148).In
acute toxicity study, all the doses (2, 4, 8 and 20
ml/kg bw) of petroleum ether extract of Hibiscus
sabdariffa seeds were found to be non-toxic for rats.
No animal mortality was observed after receiving
petroleum ether extract up to the dose of 20 ml/kg
bw(44).Hibiscus sabdariffa calyces extract, 0.6g,
1.2g and 1.8g in 100ml distilled water for rats,
caused no significant difference in weight of the
organs when compared with the control, but there
were inflammations on the liver tissues. Kidney
organs also showed no difference in their normal
gross anatomical features size, color, and
consistency(32). The effects of a 90-day oral
administration of water and alcohol extracts of dried
calyx of Hibiscus sabdariffa were evaluated in albino
rats. Significant reductions in the erythrocyte count
with no difference in total leucocyte count were
observed. The activity of aspartate aminotransferase
was enhanced by the administration of aqueous and
50% ethanol extract with a significant increase in its
level at higher doses (P<0.05). Alanine
aminotransferase and creatinine levels were
significantly affected by all the extracts at the
different dose levels. Aqueous extracts exhibited a
significant increase in creatinine levels (P<0.05) at
higher doses. No significant histopathological
changes were observed, although there was a
significant reduction in the weight of the spleen of
the animals administered with ethanol and water
extracts when compared with the control (P<0.01).
Other organs were of the same relative
weight(175).Acute and chronic toxicities of the
water extract from calyces of Hibiscus sabdariffa
were studied in rats. After 14 days of a single oral
administration of the water extract 5g/ kg bw, no
signs and differences of the weights or behaviour
were observed compared to the control rats. The
chronic toxicity was determined by oral feeding both
male and female rats daily with the extract at the
doses of 50, 100, and 200 mg/kg body weight for
270 days. The examinations of signs, animal
behaviour and health monitoring showed no defects
in the test groups compared to the control groups.
Results showed no differences from the control
groups in haematology, blood clinical chemistry,
and microanatomy(176). The aqueous fraction of
an aqueous-alcoholic extract of Hibiscus sabdariffa
calyces was given to Wistar albino rats orally, to
study the toxicity of the extract. Results of the study
showed that the levels of serum aspartate
aminotransferase and alanine amino transferase
were significantly (P<0.05) increased in all the
treatments compared with the control group.
However, the serum levels of alkaline phosphatase,
and lactate dehydrogenase were not significantly
(P>0.05) affected. Only the group with 15 doses
had their serum level of albumin significantly
(P<0.05) increased. However, the results of
histopathological studies showed that both the livers
and hearts gave no pathological features for all the
treatments(177). Clinical trials showed that ingestion
of Hibiscus sabdariffa was well tolerated and there
was no adverse effect during the
trials(119,117,118). The health benefit effects of
Hibiscus sabdariffa dried calyces beverage on some
clinical, biochemical and hematological parameters
were investigated in humans. A drink was prepared
for 32 male volunteers. Each participant consumed
500 ml twice a day (in the morning and in the
evening) as supplement beverage for two weeks.
The anthropometrics (age, height, weight, body
mass index (BMI)), clinical (systolic and diastolic
blood pressure), hematological (RBC, Hb, PCV,
MCV, MCH, MCHC, WBC, Lymphocytes, MID cells,
Granulocytes, platelet and MPV) and biochemical
(TC, HDL-C, LDL-C, TG, serum iron, blood glucose,
creatinine, urea, ASAT and ALAT) parameters were
determined in the blood on days 0 and at the end of
each week. A significant increase of RBC, Hb, PCV,
MPV, HDL-C, TG and creatinine and a significant
decrease of WBC, MID cells, LDL-C and TC
(P<0.05) were observed during the study period.
Furthermore, there was no significant change on
BMI, MCV, MCH, MCHC, lymphocyte, granulocyte,
platelet, serum iron, blood glucose, ASAT, ALAT and
urea levels. The authors concluded that Hibiscus
sabdariffa dried calyces drink can be safely used. It
also revealed good cholesterol lowering potential.
No hepatoxicity and no kidney damage have been
observed(178).
Dose
In clinical investigating of the hypotensive effect of
plant, daily dose of dry calyx 10 g (equivalent to
anthocyanin 9.6 mg) as an infusion in water, or
total anthocyanin 250 mg per dose were used for 4
weeks. The pharmacokinetics in healthy volunteers
revealed a half-life of 2.6 hours and a maximum
excretion at 1.5 to 2 hours(89,179,180).
Conclusion
This review discusses the chemical constituent,
pharmacological and therapeutic effects of Hibiscus
Ali et al / Pharmacological and therapeutic importance of Hibiscus sabdariffa- A review
468|International Journal of Pharmaceutical Research | Apr-june 2018 | Vol 10 | Issue 3
sabdariffa as promising herbal drug because of its
safety and effectiveness.
Author’s contribution
Al-Snafi is the single author of the manuscript,
drafted the and approved the manuscript.
Conflict of interests
The author declared no competing interests.
Consent for publication
The manuscript didn't contain any individual persons
data.
Funding/Support
The author received no fund from any source.
Ethical considerations
The work is a review, the author didn't perform
experimental and clinical work. Ethical issues
(including plagiarism, misconduct, data fabrication,
falsification, double publication or submission,
redundancy) have been completely observed by the
author.
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... Body weight, serum LDL cholesterol and triglyceride levels decreased in both groups, there were no significant differences between the experimental and placebo group. At a dose of 1 gm/day, Hibiscus sabdariffa leaf extract did not appear to have a blood lipid lowering effect (173)(174) . ...
... Polysaccharide fraction from Lycium barbarum (LBP) in addition to its hypoglycemic effect in diabetic mice, it also significant decrease total cholesterol and triglyceride (174) .Basal diet supplemented with 10 and 20 g/kg bw dry wolfberry fruit powder for 4 weeks also decreased TG, TC, VLDL and VLDL and increased the mean values of HDL in diabetic rats (207) . ...
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... It also revealed good cholesterol lowering potential. No hepatoxicity and no kidney damage have been observed (245)(246) . ...
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Plants are a valuable source of a wide range of secondary metabolites, which are used as pharmaceuticals, agrochemicals, flavours, fragrances, colours, biopesticides and food additives. In the current review, PubMed, Web Science, Science Direct, Researchgate, Academia. edu and Scopus were searched to determinethe medicinal plantswhich pass the clinical trials with documented efficacy and safety.
... Hibiscus sabdariffa crude extract induced mainly endothelium-dependent relaxant effects on isolated thoracic aorta of male Wistar rats. The endothelium-dependent relaxations result from NOS activation (93)(94) . ...