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International Journal of Pharmacognosy and Phytochemical Research 2016; 8(7); 1200-1208
ISSN: 0975-4873
Review Article
*Author for Correspondence: erchan@yahoo.com
A Review on the Phytochemistry and Pharmacology of two Hibiscus
Species with Spectacular Flower Colour Change: H. tiliaceus and H.
mutabilis
Eric W.C. Chan1*, S.K. Wong2, H.T. Chan3
1Faculty of Applied Sciences, UCSI University, 56000 Cheras, Kuala Lumpur, Malaysia.
2School of Science, Monash University Sunway, 46150 Petaling Jaya, Selangor, Malaysia.
3Secretariat, International Society for Mangrove Ecosystems, c/o Faculty of Agriculture,
University of the Ryukyus, Okinawa, 903-0129 Japan.
Available Online: 12th July, 2016
ABSTRACT
Among the Hibiscus species, H. tiliaceus and H. mutabilis display spectacular flower colour change. In this short review,
the current knowledge on their phytochemistry and pharmacology is updated, and their botany and uses described. With
phytosterols, triterpenes, triterpenoids, coumarins, amides, phenolic acids, and anthocyanins as chemical constituents, H.
tiliaceus has pharmacological properties of antioxidant, antibacterial, tyrosinase inhibitory, cytotoxic,
immunomodulatory, anti-inflammatory, analgesic, anti-diabetic, hypolipidemic, anti-tumour and anthelmintic activities.
Chemical constituents of H. mutabilis include flavonoids, flavonol glycosides and anthocyanins with pharmacological
properties of antioxidant, antibacterial, anti-inflammatory, analgesic, hepatoprotective, antiviral, anticancer, filaricidal,
anti-allergy and anti-diabetic activities. Both H. tiliaceus and H. mutabilis have anti-inflammatory, analgesic and anti-
diabetic activities in common. A quick literature search showed that at least five other species of Hibiscus share these
pharmacological properties. Included in the search were extracts or compounds responsible and their mechanisms of
action.
Keywords: Hibiscus tiliaceus; sea hibiscus; Hibiscus mutabilis; confederate rose; anti-inflammatory; analgesic.
INTRODUCTION
The genus Hibiscus (Malvaceae) comprises some 275
species in the tropics and sub-tropics of which 43 species
are found in the Malesian region1. Documented in the
Flora of China, 12 Hibiscus species are endemic and four
are introduced in China2. Leaves of Hibiscus are simple,
lobed, alternately or spirally arranged and have paired
stipules3. Flowers are radially symmetrical with cup-
shaped calyx, five petals joined at the base, style bearing
many stamens, and stigma with five hairy lobes. Flowers
of most Hibiscus species have a remarkable colour
pattern with the inner base of petals forming a deep-
coloured heart4. Another feature of Hibiscus is flower
colour change which can be spectacular in some species.
Hibiscus is widely cultivated as ornamental, food, and
medicinal plants1. Leaves of some species are consumed
as vegetable, and stem fibres are also used for pulp and
paper. The mucilage is used as emollient and demulcent
for abscesses, ulcers, cutaneous infections, swellings,
boils and mumps. In South, Southeast and East Asia, the
mucilage is believed to have a cooling effect, and is used
for healing burns and scalds. The mucilage is also used
as medication for treating cough, bronchitis, dysuria and
menorrhagia. Midwives apply the mucilage to facilitate
delivery of newborn. Hibiscus species have been reported
to possess a wide range of pharmacological properties
such as antioxidant, antibacterial, antihypertensive, anti-
inflammatory, antipyretic, anti-cancer, anti-tumour,
hepatoprotective, hypoglycaemic, antidiabetic,
anticonvulsant, antihelminthic, anti-spermatogenic and
antimutagenic activities5,6. In this short review, the major
chemical constituents and pharmacological properties of
H. tiliaceus and H. mutabilis, two Hibiscus species with
spectacular flower colour change, are updated with some
description of their botany and uses. Both species have
been documented in a book on edible medicinal and non-
medicinal plants7. A review of the pharmacology and
secondary metabolites of ten Hibiscus species has
included H. tiliaceus amongst them8, and an overview on
the phytochemistry and pharmacology of H. mutabilis has
been documented9. Nevertheless, this review is still
deemed appropriate and relevant, particularly the
discussion on other Hibiscus species sharing similar
pharmacological properties as H. tiliaceus and H.
mutabilis, and their possible modes of action. There is a
concurrent documentation in IJPPR where we reviewed
the phytochemistry and pharmacology of H. taiwanensis
and H. schizopetalus, two lesser-known Hibiscus species.
HIBISCUS TILIACEUS
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Botany and uses
Hibiscus tiliaceus L. (sea hibiscus) is a coastal plant of
the tropics and sub-tropics10. Associated with mangroves,
the species is a fast-growing tree that can grow up to 20
m tall. Leaves are heart-shaped. Flowers are bell-shaped
with maroon-coloured heart and stigma. They are yellow
in the morning, turning orange-red in the evening, and
mauve the next morning (Figure 1). In Chinese folk
medicine, the root of H. tiliaceus has been used as an
antifebrile and emetic, and the leaf and bark have been
used for the treatment of cough and bronchitis11. Flowers
of H. tiliaceus are used to treat ear infections12, and in
birth control in countries of Asia and Africa13. In Indo-
China, leaves are used as a laxative1. In the Philippines,
the bark has been used for treating dysentery, and in
Papua New Guinea, a decoction of leaves is taken for
sore throat, pneumonia, cough, tuberculosis and
diarrhoea.
Phytochemistry
Phenolics of p-coumaric acid, fumaric acid, kaempferol,
kaempferol-3-O-D-galactoside, quercetin and quercetin-
3-O-D-galactoside have been reported in fruits of H.
tiliaceus14. In flowers of H. tiliaceus, cyanidin-3-
glucoside is the major anthocyanin4. Other compounds
identified in the flowers were saturated hydrocarbons of
15−34 carbons, methyl ester of fatty acids, α-tocopherol
and phytosterols15. Recently, one anthocyanin (cyanidin
3-O-sambubioside) and four flavonols have been isolated
from the flowers16. From the stem and bark, a new
friedelane-type triterpene (27-oic-3-oxo-28-friedelanoic
acid) and eight known triterpenoids have been isolated17.
All the compounds were reported from H. tiliaceus for
the first time. Out of eight triterpenoids isolated from
leaves of H. tiliaceus, three with the rare nigrum skeleton
were new18. Phytochemical analysis of H. tiliaceus led to
the isolation of 10 compounds (ergosta-4,6,8, friedelin,
germanicol, glutinol, lupeol, pachysandiol, β-sitosterol,
stigmast-4,22-dien-3-one, stigmast-4-en-3-one,
stigmasterol and 22-tetraen-3-one) from the stem and
bark19, and 14 compounds (azelaic acid, cleomiscosin C,
daucosterol, friedelin, fumaric acid, hibiscolactone,
kaempferol, quercetin, rutin, scopoletin, β-sitosterol,
succinic acid, syriacusin A and vanillin) from the leaf and
stem20. A new coumarin (hibiscusin) and a new amide
(hibiscusamide) together with 11 known compounds
(vanillic acid, syringic acid, p-hydroxybenzoic acid, p-
hydroxybenzaldehyde, scopoletin, N-trans-
feruloyltyramine, N-cis-feruloyltyramine, β-sitosterol,
stigmasterol, β-sitostenone and stigmasta-4,22-dien-3-
one) have been isolated from the stem wood of H.
tiliaceus21. A continuing phytochemical study on the leaf
and branch extracts of H. tiliaceus yielded two new
tetracyclic triterpenoids (tiliacol A and tiliacol B)
together with one known analog of tiliacol A22.
Quantified using HPLC-DAD, the ethanol leaf extract of
H. tiliaceus growing in Bangladesh yielded phenolic
compounds of catechin, rutin, quercetin, and ellagic acid
with contents of 99, 79, 69 and 59 mg/100 g,
respectively23.
Pharmacology
Antioxidant properties
Out of leaves and flowers of six Hibiscus species
screened for total phenolic content (TPC) and free radical
scavenging (FRS), extracts of H. tiliaceus ranked first
with outstanding values24,25. TPC and FRS of H. tiliaceus
leaves were 2.4 and 2.7 times those of H. mutabilis,
which ranked second. Flowers were 4.9 and 5.6 times
higher. Out of leaves of nine coastal plant species
screened for antoxidant properties, TPC and FRS values
of H. tiliaceus were the highest with young leaves having
slightly higher values than mature leaves26. A similar
trend was also observed for total flavonoid content and
ferric reducing power. A comparison between the
antioxidant properties of coastal and inland populations
of H. tiliaceus did not show any distinct variation for both
leaves and flowers27. With greater UV radiation in coastal
areas, there was no evidence that coastal populations have
stronger antioxidant properties. Flower extracts of H.
tiliaceus have antioxidant effect protecting several strains
of yeast cells against cytotoxicity of hydrogen peroxide
(H2O2) and tert-butyl-hydroperoxide (TBHP),14 and
showed antigenotoxic and antimutagenic effects against
oxidative DNA damage induced by H2O2 and TBHP in
V79 cells28. The same group of researchers also reported
that the flower methanol extract of H. tiliaceus had
antidepressant-like influence on male Swiss albino mice
without sedative side effect29.
Antibacterial activity
The antibacterial activity of the methanol leaf extract of
H. tiliaceus has been reported with minimum inhibitory
doses of 1.0, 0.5 and 0.25 mg/disc against Gram-positive
bacteria of Bacillus cereus, Micrococcus luteus and
Staphylococcus aureus, respectively25. No inhibition was
observed for Gram-negative bacteria of Escherichia coli,
Pseudomonas aeruginosa and Salmonella choleraesuis.
The ethanol extract of dried H. tiliaceus leaves showed
activity against S. aureus, E. coli and Salmonella
paratyphi with diameters of inhibition zones of 9.0 mm
and 12–15 mm at doses of 250 and 500 μg/disc,
respectively30.
Anti-tyrosinase activity
Leaf extracts of H. tiliaceus showed strong anti-
tyrosinase activity. Out of 39 seashore plant species, and
36 edible and medicinal plant species found in Okinawa,
Japan, leaves of H. tiliaceus had the highest tyrosinase
inhibition31,32. Of four species of Hibiscus tested, leaves
of H. tiliaceus had the strongest anti-tyrosinase activity
(42%) followed leaves by H. mutabilis (25%)25. The
value of H. tiliaceus was comparable to leaves of guava
(41%) used as positive control.
Cytotoxic activity
Hibiscusamide, N-trans-feruloyltyramine and N-cis-
feruloyltyramine isolated from the stem wood of H.
tiliaceus had cytotoxic activity against P-388 and/or
HT-29 cells with IC50 values < 4 g/ml21. Hibiscusamide
was the most cytotoxic with IC50 values of 1.7 and 3.8
g/ml, respectively. Of the three tetracyclic triterpenoids
isolated from the leaf and branch extracts of H. tiliaceus,
the analog of tiliacol A showed potent cytotoxicity
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against P388 and HeLa cells with IC50 values of 11.2 and
11.5 mmol/L, respectively22.
Immunomodulatory effects
Wistar rats administered orally with methanol leaf extract
of H. tiliaceus at doses of 250 and 500 mg/kg/day for 28
days showed a significant increase in the production of
circulating antibody titer in response to sheep red blood
cells, a significant increase in primary and secondary
hemagglutination antibody titer, and enhanced production
of red blood cells, white blood cells and hemoglobin33.
Evidently, oral administration of the extract has an
immuno-modulatory effects in the Wistar rats.
Anti-inflammatory and analgesic effects
Successive methanol, petroleum ether, and chloroform
leaf extracts of H. tiliaceus were tested for anti-
inflammatory and analgesic effects in mice at oral doses
of 250 and 500 mg/kg34. Results showed significant anti-
inflammatory activity against carragennan-induced paw
oedema after 2 and 3 h, and significantly inhibited acetic
acid-induced abdominal writhing after 1 h. Ranking of
effectiveness of extracts was methanol > chloroform >
petroleum ether. The methanol wood extract of H.
tiliaceus at 200 and 400 mg/kg was reported to have anti-
inflammatory and analgesic effects in mice35.
Anti-diabetic and hypolipidemic effects
In another study, the methanol flower extract of H.
tiliaceus was evaluated for anti-diabetic and
hypolipidemic effects using streptozotocin-induced
diabetic Wistar rats orally administered with the extract at
doses for 250 and 500 mg/kg for 21 days36. The extract
showed significant anti-diabetic activity with
improvement in body weight, reduction in serum
cholesterol and triglycerides, and improvement in high
density lipoprotein (HDL)-cholesterol level.
Anti-tumour activity
The anti-tumour activity of the aqueous root extract of H.
tiliaceus has been reported37. Swiss albino mice bearing
Dalton’s ascitic lymphoma (DAL) were inoculated with
the extract at a dose of 200 mg/kg/day for nine days,
mean survival time and peritoneal cell counts were
Figure 1: Freshly open flower of Hibiscus tiliaceus is yellow in the morning (left) and mauve the next morning (right).
Figure 2: Flower of Hibiscus mutabilis is white (left) in the morning and pink (right) in the afternoon.
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enhanced, and tumour cell growth was found to be
inhibited. The results indicated that the extract treated
groups were able to reverse their haematological
parameters altered by DAL cells within 14 days. In the
Traditional Chinese Medicines (TCM) database, H.
tiliaceus has been recorded as an anti-tumour agent,
which has been validated by western medicine in the
Comprehensive Medicinal Chemistry (CMC) database38.
Anthelmintic activity
The anthelmintic activity of leaf and wood extracts of H.
tiliaceus has been reported39. Tested against Pheretima
posthuma based on time of paralysis and time of death
using 10−40 mg/ml of extracts, good activity was shown
by the ethyl acetate leaf extract (28−46 and 45−74 min)
and petroleum ether wood extract (29−45 and 47−78
min), respectively.
HIBISCUS MUTABILIS
Botany and uses
Hibiscus mutabilis L. (confederate rose) is an inland
woody shrub (1.5−4.0 m tall) that is native to China and
widely cultivated in Southeast Asia1. Leaves are broadly
ovate with mostly five triangular lobes. Although H.
mutabilis produces large and beautiful flowers, its
constraint as ornamental plants is the frequent and
unsightly infestation of whiteflies.
Flower colour change in H. mutabilis is most spectacular.
Flowers are white in the morning, pink in the afternoon,
and red in the evening (Figure 2). Temperature may be an
important factor affecting the rate of colour change as
white flowers kept in the refrigerator remain white until
they are taken out to warm, whereupon they slowly turn
pink3. Leaves and flowers are emollient and cooling, and
are used to treat swellings and skin infections1. Midwives
use mucilage from flowers and leaves to facilitate
delivery during labour.
Phytochemistry
Phytochemical analyses of H. mutabilis are focused on
the flowers, which are white in the morning, pink during
noon and red in the evening. Analysis of petals showed
the presence of flavonol glycosides40. Anthocyanins,
absent in the morning, were found during noon and in the
evening. They were cyanidin 3,5-diglucoside and
cyanidin 3-rutinoside-5-glucoside. Studies have shown
that the total anthocyanin content in the evening was 3-
fold greater than that at noon. Flavonols of noon and
evening flowers were identical to those of morning
flowers. Since there was no reduction in flavonol content,
it was suggested that the anthocyanins were synthesized
independently. The main pigments of white and red
flowers of H. mutabilis were due to quercetin 3-
sambubioside and cyanidin 3-sambubioside,
respectively4. These compounds were previously
identified as quercetin 3,5-diglucoside and cyanidin 3,5-
diglucoside. As the glycoside compounds were identical,
there is a possibility that anthocyanins are formed through
direct conversion of flavonol glycosides. A related study
reported that colour change of H. mutabilis flowers from
white to red is due to the accumulation of cyanidin-3-
sambubioside41. At the intial and rapid phase of pigment
accumulation, phenylalanine ammonia-lyase (PAL)
activity in the intact petals increases rapidly to seven
Table 1: Hibiscus species with anti-inflammatory, analgesic and anti-diabetic properties.
Hibiscus species
Plant part
Extract/compound
Activity
Reference
H. tiliaceus
Leaf
Wood
Flower
Successive
Methanol
Methanol
Anti-inflammatory, analgesic
Anti-inflammatory, analgesic
Anti-diabetic, hypolipidemic
34
35
36
H. mutabilis
Leaf
Bark
Leaf
Ethanol
Successive
Methanol
Anti-inflammatory
Analgesic
Anti-diabetic
47
48
53,54
H. cannabinus
Leaf
Leaf
Successive
Methanol
Anti-inflammatory, analgesic
Anti-diabetic
55
56
H. rosa-sinensis
Leaf
Leaf, flower
Leaf
Flower
Flower
Flower
Methanol
Ethanol
Aqueous, ethanol
Ethanol
Aqueous
Ethanol
Anti-inflammatory, analgesic
Anti-inflammatory
Analgesic
Anti-inflammatory, analgesic
Hypoglycaemic, hypolipidemic
Anti-diabetic
57
58
59
60
61
62
H. sabdariffa
Leaf
Seed
Calyx
Calyx
Calyx
Methanol
Petroleum ether
D, DS
Ethanol
Methanol
Anti-inflammatory
Anti-inflammatory, analgesic
Anti-inflammatory
Hypolipidemic
Hypoglycaemic, hypolipidemic
63
64
65
66
67
H. schizopetalus
Leaf
Leaf, flower
Leaf, flower
Successive
Methanol
Methanol
Anti-inflammatory
Analgesic
Hypoglycaemic, hypolipidemic
68
69
70
H. taiwanensis
Stem
Stem
Stem
Aqueous
Acetone
SA
Anti-inflammatory, analgesic
Hypoglycaemic
Hypoglycaemic
71
72‒74
75
D = Delphinidin, DS = Delphinidin 3-sambubioside, SA = syringaldehyde
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times its initial level and then decreases when the flower
senesces. In excised petals, the PAL inhibitor (L-α-
aminooxy-β-phenylpropionic acid) suppresses pigment
formation. Findings showed that the rapid accumulation
of cyanidin in the petals was due to de novo synthesis via
the shikimate and phenylpropanoid pathways, and ruled
out the synthesis from precursors such as
hydroxycinnamic acid conjugates or colourless
flavonoids. In addition to cyanidin 3-xylosylglucoside
and cyanidin 3-glucoside, the red flowers of H. mutabilis
contained quercetin 3-sambubioside, isoquercitrin,
hyperin, guaijaverin and kaempferol glycosides42.
Bioassay-directed fractionation of the methanol extract of
petals of H. mutabilis led to the isolation of mutabiloside,
a new flavonol triglycoside, together with four known
flavonols, which included quercetin and hyperoside43.
From the ethanol stem extract of H. mutabilis, a new
flavanone glycoside has been isolated44. Recently,
steppogenin, genistein, salicylic acid, rutin,
potengriffioside A, kaempferol 3-O-rutinoside and
emodin were identified from the ethanol leaf extract of H.
mutabilis45. The first two compounds are new to the
species.
Pharmacology
Antioxidant properties
Out of the six Hibiscus species screened for antioxidant
properties of total phenolic content and free radical
scavenging values of H. mutabilis leaves and flowers
ranked second and fourth, respectively24. Their values
were 2.4, 2.7, 4.9 and 5.7 times lower than leaves and
flowers of H. tiliaceus. Under laboratory conditions,
flower colour change of H. mutabilis was slower than that
of flowers under outdoor conditions. Red flowers had
higher values than pink and white flowers. Based on total
anthocynanin content, red flowers were 2.7 times that of
pink flowers and 7.7 times that of white flowers. Overall
ranking of the antioxidant properties of H. mutabilis
flowers was red > pink > white.
Antibacterial activity
The methanol and ethyl acetate extracts of H. mutabilis
have been reported to possess antibacterial activity46. At
8.0 mg/disc, the extracts inhibited Bacillus subtilis,
Klebsiella pneumoniae, Proteus vulgaris, Salmonella
typhi, E. coli and S. aureus with zones of inhibition
ranging from 10−15 mm.
Anti-inflammatory effects
Recently, the anti-inflammatory effects of leaves of H.
mutabilis have been reported47. Results showed that the
ethanol leaf extract had no apparent effect on the viability
of RAW264.7 cells but TNF-α, IL-6 and NO release in
LPS-induced RAW264.7 cells and in the serum of
experimental arthritic rat were significantly inhibited.
Analgesic activity
The analgesic activity of petroleum ether, ethyl acetate,
and methanol bark extract of H. mutabilis was evaluated
in mice using the hot plate method and acetic acid-
induced writhing test48. All extracts showed analgesic
activity at 50 and 100 mg/kg respectively. In the hot plate
method, the petroleum ether extract showed the highest
increase in reaction time. The methanol extract showed
more inhibitory effect on writhing induced by acetic acid
as compared to other extracts.
Hepatoprotective effect
The hepatoprotective effect of ethanol leaf, stem, and
flower extracts of H. mutabilis against CCl4-induced
hepatic injury in rats has been reported49. Administration
of CCl4 significantly increased the release of alanine
transaminases, aspartate transaminases and alkaline
phosphatase. Results showed that 200 mg/kg of the
extracts administered to the rats for seven days
significantly modulated these enzymes in blood serum to
normal values. Research by the same group of scientists
showed that the ethanol leaf and flower extracts of H.
mutabilis possessed antimitotic activity50. Roots of Allium
cepa incubated with the extracts for three days were
shorter in root length and fewer in number. The
antimitotic activity of the extracts was comparable with
paracetamol as the standard drug used.
Antiviral and anticancer activities
A hexameric lectin isolated from H. mutabilis seeds
showed potent inhibition of HIV-1 reverse transcriptase
with IC50 value of 0.2 µM51. The anti-proliferative
activity of the lectin towards HepG2 (40% inhibition) and
MCF-7 (50% inhibition) human cancer cells was however
weak at 100 µM.
Filaricidal activity
Recently, the methanol leaf extract of H. mutabilis and
the isolated ferulic acid were reported to display
significant filaricidal activity against microfilaria and
adult worms of Setaria cervi, a bovine filarial parasite52.
Extreme cellular disturbance characterized by chromatin
condensation, in situ DNA fragmentation and
nucleosomal DNA laddering was observed in ferulic
acid-treated adult worms.
Anti-allergy effects
Among the flavonol derivatives isolated from the
methanol extract of flower petals of H. mutabilis,
mutabiloside showed significant allergy-preventive
effects using an in vivo assay that monitors the decrease
in blood flow at the tail vein of mice subjected to egg
white lysozyme sensitization43.
Anti-diabetic properties
Ferulic acid and caffeic acid identified from the ethyl
acetate fraction of the methanol leaf extract of H.
mutabilis using RP-HPLC-DAD were found to inhibit α-
glucosidase, suggesting they possess anti-diabetic
properties53. Ferulic acid purified from the methanol leaf
extract of H. mutabilis has been reported to inhibit lipid
induced insulin resistance in skeletal muscle cells54. In
high fat diet diabetic rats, ferulic acid (0.6 mg/kg) was
orally administered at alternative days for 15 days,
reduced blood glucose level and enhanced lipid uptake
activity of adipocytes isolated from adipose tissue. As
skeletal muscle and adipose tissues are known to be
important insulin target sites the study concluded that
ferulic acid showed promise as a good therapeutic choice
for treatment of type-2 diabetes.
DISCUSSION
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IJPPR, Volume 8, Issue 7: July 2016 Page 1205
Although Hibiscus species are endowed with diverse
chemical compounds that have different pharmacological
properties, both H. tiliaceus and H. mutabilis have anti-
inflammatory, analgesic and anti-diabetic activities in
common (Table 1). A quick literature search revealed that
at least five other Hibiscus species (H. cannabinus, H.
rosa-sinensis, H. sabdariffa, H. schizopetalus and H.
taiwanensis) share similar pharmacological activities.
Only a few studies were conducted on the modes of
action of extracts or compounds responsible.
Polyphenols extracted from H. sabdariffa has the ability
to prevent inflammation by impairing cyclooxygenase-2
(COX-2) induction, and by down-regulating Jun N-
terminal kinase (JNK) and p38 mitogen-activated protein
kinase76. In lipopolysaccharide (LPS)-stimulated mouse
macrophages, the aqueous stem extract of H. taiwanensis
inhibited nitric oxide (NO), tumor necrosis factor and
prostaglandin E2 production71. The extract blocked
protein expression of inducible nitric oxide synthase
(iNOS) and cyclooxygenase-2 (COX-2), and elevated
heme oxygenase-1 (HO-1). In the animal test, the extract
decreased paw oedema and increased antioxidant
enzymes activities in the paw tissue. The extract
decreased iNOS and COX-2, and increased HO-1
expressions in the oedema paw. Recently, the
antiinflammatory activity and molecular mechanisms of
delphinidin 3-sambubioside (DS) and delphinidin (D)
extracted from calyces of H. sabdariffa have been
investigated65. The cell model, DS and D reduced the
levels of inflammatory mediators induced by LPS, and
downregulated NF-kB pathway and MEK1/2-ERK1/2
signaling. In the animal model, DS and D reduced the
production of IL-6, MCP-1 and TNF-α and ameliorated
mouse paw oedema induced by LPS. Syringaldehyde
(SA) isolated from stems of H. taiwanensis has the ability
to lower hyperglycemia75. The compound significantly
decreased post-prandial plasma glucose in rats, while
plasma insulin was not modified. Administration of SA
for 3 days in streptozotocin-induced diabetic rats resulted
in marked reduction of PEPCK expression in the liver
and increased expression of GLUT 4 in the skeletal
muscle, suggesting that SA can increase glucose uptake
and lower hyperglycemia in diabetic rats. Many herbs
used as Traditional Chinese Medicine (TCM) have also
shown to inhibit inflammation, pain and swelling in
different organs of the human body77,78, and to prevent
and treat diabetes with clinical trials79. It would be
interesting to compare the mechanisms of action of
Hibiscus species with those of TCM herbs.
CONCLUSION
Both H. tiliaceus and H. mutabilis have anti-
inflammatory, analgesic and anti-diabetic activities in
common. A quick literature search showed that at least
five other Hibiscus species (H. cannabinus, H. rosa-
sinensis, H. sabdariffa, H. schizopetalus and H.
taiwanensis) share similar pharmacological properties. Of
the two species reviewed, H. tiliaceus is the most studied
with publications by scientists from at least six countries.
Publications on H. mutabilis came from at least four
countries with several recent papers on its
pharmacological properties. The current isolation of new
and known compounds from Hibiscus species has been
mostly associated with their medicinal values. There is
hardly any work done relating phytochemistry to their
biological and ecological functions. It is time that the
biologists and ecologists work with the natural product
chemists and pharmacologists on these ornamental, food
and medicinal plants.
REFERENCES
1. Dasuki UA. Hibiscus. In: van Valkenburg JLCH,
Bunyapraphatsara N, eds. Plant Resources of South-
East Asia No. 12(2): Medicinal and Poisonous Plants
2. Leiden: Backhuys Publisher, 2001; 297-303.
2. Tang Y, Gilbert MG, Dorr LJ. Hibiscus. In: Flora of
China, Vol. 12. Beijing and St. Louis: Science Press
and Missouri Botanical Garden Press, 2007; 286-294.
3. Ng FSP. Malvaceae. In: Tropical Horticulture and
Gardening. Kuala Lumpur: Clearwater Publications,
2006; 240−245.
4. Lowry JB. Floral anthocyanins of some Malesian
Hibiscus species. Phytochemistry 1976; 15: 1395-
1396.
5. Kumar A, Singh A. Review on Hibiscus rosa-
sinensis. Int. J. Res. Pharm. Biomed. Sci. 2012; 3(2):
534-538.
6. Salem MZM, Olivares-Pérez J, Salem AZM. Studies
on biological activities and phytochemicals
composition of Hibiscus species ‒ A review. Life Sci.
J. 2014; 11(5): 1-8.
7. Lim TK. Hibiscus. In: Edible Medicinal and Non
Medicinal Plants Vol. 8, Flowers. Dordrecht,
Heidelberg, London and New York: Springer Science
and Business Media BV, 2014; 300-394.
8. Maganha EG, Halmenschlager RDC, Rosa RM,
Henriques JAP, de Paula Ramos ALL, Saffi J.
Pharmacological evidences for the extracts and
secondary metabolites from plants of the genus
Hibiscus. Food Chem. 2010; 118: 1-10.
9. Raut DN, Mandal SC, Pal SC. Phytochemical and
pharmacological overview of Hibiscus mutabilis Linn.
Int. J. Pharm. Res. Biosci. 2014; 3: 236-241.
10. Chan HT, Baba S. Manual on Guidelines for
Rehabilitation of Coastal Forests Damaged by
Natural Hazards in the Asia-Pacific Region. Japan:
International Society for Mangrove Ecosystems
(ISME) and International Tropical Timber
Organization (ITTO), 2009.
11. Kan WS. Malvaceae. In: Pharmaceutical Botany. 4th
Ed. Taipei: National Research Institute of Chinese
Medicine, 1997; 333-339.
12. Bandaranayake WM. Traditional and medicinal uses
of mangroves. Mangr. Salt Marsh 1998; 2: 133-148.
13. Rosa RM, Melecchi MIS, Halmenschlager RDC,
Abad FC, Simoni CR, Caramão EB, Henriques JAP,
Saffi J, de Paula Ramos, ALL. Antioxidant and
antimutagenic properties of Hibiscus tiliaceus L.
methanolic extract. J. Agric. Food Chem. 2006; 54:
7324-7330.
Eric et al. / A Review on the…
IJPPR, Volume 8, Issue 7: July 2016 Page 1206
14. Subramanian S, Nair AGR. Chemical constituents
of the fruit of Hibiscus tiliaceus. Curr. Sci. 1973;
42: 770-771.
15. Melecchi MIS, Péres VF, Dariva C, Zini PP, Filho IN,
Caramão EB. Optimization of the sonication
extraction method of Hibiscus tiliaceus L. flowers.
Ultrason. Sonochem. 2006; 13: 242-250.
16. Shimokawa S, Iwashina T, Murakami N. Flower color
changes in three Japanese hibiscus species: further
quantitative variation of anthocyanin and flavonols.
Nat. Prod. Commun. 2015; 10: 451-452.
17. Li L, Huang X, Sattler I, Fu H, Grabley S, Lin W.
Structure elucidation of a new friedelane triterpene
from the mangrove plant Hibiscus tiliaceus. Magn.
Reson. Chem. 2006; 44: 624-628.
18. Feng C, Li XM, Ji NY, Wang BG. Triterpenoids from
the mangrove plant Hibiscus tiliaceus. Helv. Chim.
Acta 2008; 91: 850-855.
19. Wang ZZ, Li J, Tang XL, Li GQ. Triterpenes and
steroids from semi-mangrove plant Hibiscus tiliaceus.
Chin. J. Nat. Med. 2011; 9: 190-192.
20. Zhang XP, Zhang JQ, Pei YH, Xu XD, Tan YF, Kang
SL, Liu MS. Chemical constituents from Hibiscus
tiliaceus. Chin. Trad. Herbal Drug 2012; 43: 440-443.
21. Chen JJ, Huang SY, Duh CY, Chen IS, Wang TC,
Fang HY. A new cytotoxic amide from the stem wood
of Hibiscus tiliaceus. Planta Med. 2006; 72: 935-938.
22. Cheng CL, Wang ZZ, Li PL, Zhang XW, Wu RC,
Zhu HY, Tang XL, Li GQ. Tetracyclic triterpenoids
isolated from semi-mangrove plant Hibiscus tiliaceus.
Chin. Chem. Lett. 2013; 24: 1080-1082.
23. Hossain H, Akbar PN, Rahman SE, Yeasmin S, Khan
TA, Rahman MM, Jahan IA. HPLC profiling and
antioxidant properties of the ethanol extract of
Hibiscus tiliaceus leaf available in Bangladesh. Eur.
J. Med. Plants 2015; 7: 7-15.
24. Wong SK, Lim YY, Chan EWC. Antioxidant
properties of Hibiscus: Species variation, altitudinal
change, coastal influence and floral colour change. J.
Trop. For. Sci. 2009; 21: 307-315.
25. Wong SK, Lim YY, Chan EWC. Evaluation of
antioxidant, antityrosinase and antibacterial activities
of selected Hibiscus species. Ethnobot. Leaflets 2010;
14: 781-796.
26. Nivas MD, Sonar BA, Shaikh SS, Patil UH,
Dattatraya KG, Niranjana C, Anjali BS, Chavan PD.
Screening of some coastal plant resources for their
antioxidant potential, total polyphenol and flavonoid
content. J. Pharmacogn. 2010; 2(7): 151-156.
27. Wong SK, Chan EWC. Antioxidant properties coastal
and inland populations of Hibiscus tiliaceus.
ISME/GLOMIS E-J. 2010; 8: 1-2.
28. Rosa RM, Moura DJ, Melecchi MIS, dos Santos RS,
Richter MF, Camarão EB, Henriques JAP, de Paula
Ramos ALL, Saffi J. Protective effects of Hibiscus
tiliaceus L. methanolic extract to V79 cells against
cytotoxicity and genotoxicity induced by hydrogen
peroxide and tert-butyl hydroperoxide. Toxicol. In
Vitro 2007; 21: 1442-1452.
29. Vanzella C, Bianchetti P, Sbaraini S, Vanzin SI,
Melecchi MIS, Caramão EB, Siqueira IR. Anti-
depressant-like effects of methanol extract of Hibiscus
tiliaceus flowers in mice. BMC Complem. Altern.
Med. 2012; 12: 41.
30. Ramproshad S, Afroz T, Mondal B, Haque A, Ara S,
Khan R, Ahmed S. Antioxidant and antimicrobial
activities of leaves of medicinal plant Hibiscus
tiliaceus L. PharmacologyOnline 2012; 3: 82-87.
31. Masuda T, Yamashita D, Takeda Y, Yonimori S.
Screening for tyrosinase inhibitors among extracts of
seashore plants and identification of potent inhibitors
from Garcinia subelliptica. Biosci. Biotechnol.
Biochem. 2005; 69: 197-201.
32. Masuda T, Fujita N, Okada Y, Takeda Y, Yonemori
S, Nakamoto K, Kuninaga H. Tyrosinase inhibitory
activity of ethanol extracts of medicinal and edible
plants cultivated in Okinawa and identification of a
water-soluble inhibitor from the leaves of Nandina
domestica. Biosci. Biotechnol. Biochem. 2007; 71:
2316-2320.
33. Rajeswari G, Priyanka B, Amrutha RE, Rajaram C,
Kanhere RS, Kumar SN. Hibiscus tiliaceus: A
possible immuno-modulatory agent. J. Pharm. Res.
2013; 6: 742-747.
34. Sunil Kumar N, Kumar D, Kumar V. Antinociceptive
and anti-inflammatory activity of Hibiscus tiliaceus
leaves. Int. J. Pharmacogn. Phytochem. Res. 2009; 1:
15-17.
35. Borhade PS, Dalal PS, Pachauri AD, Lone KD,
Chaudhari NA, Rangari PK. Valuation of anti-
inflammatory activity of Hibiscus tiliaceus Linn
wood extract. Int. J. Res. Pharm. Biomed. Sci.
2012; 3: 1246-1250.
36. Kumar S, Kumar V, Prakash O. Antidiabetic and
hypolipidemic activities of Hibiscus tiliaceus (L.)
flower extract in streptozotocin-induced diabetic rats.
PharmacologyOnline 2010; 2: 1037-1044.
37. Sunilson AJ, Mohan S, Mohamed MA, Thomas J,
Kumari AG. Antitumour activity of Hibiscus tiliaceus
Linn. roots. Iran. J. Pharmacol. Therap. 2008; 7: 123-
125.
38. Li XJ, Zhang HY. Western-medicine-validated anti-
tumor agents and traditional Chinese medicine.
Trends Mol. Med. 2007; 14: 1-2.
39. Tambe V, Bhambar R. Phytochemical screening and
anthelmintic activity of wood and leaves of Hibiscus
tiliaceus Linn. World J. Pharm. Pharm. Sci. 2014; 3:
880-889.
40. Subramanian SS, Nair AGR. A note on the colour
change of the flowers of Hibiscus mutabilis. Curr. Sci.
1970; 39: 323-324.
41. Amrhein N, Frank G. Anthocyanin formation in
the petals of Hibiscus mutabilis L. Z. Naturforsch
1989; 44: 357-360.
42. Ishikura N. Flavonol glycosides in the flowers of
Hibiscus mutabilis f. versicolor. Agric. Biol.
Chem. 1982; 46: 1705-1706.
43. Iwaoka E, Oku H, Takahashi Y, Ishiguro K. Allergy
preventive effects of Hibiscus mutabilis ‘versicolor’
Eric et al. / A Review on the…
IJPPR, Volume 8, Issue 7: July 2016 Page 1207
and a novel allergy-preventive flavonoid glycoside.
Biol. Pharm. Bull. 2009; 32: 509-512.
44. Chauhan JS, Vidyapati TJ, Gupta AK. A new
flavanone glycoside from the stem of Hibiscus
mutabilis. Phytochemistry 1979; 18: 1766-1767.
45. Hou, Z, Liang X, Su F, Su W. Preparative isolation
and purification of seven compounds from Hibiscus
mutabilis L. leaves by two-step high-speed counter-
current chromatography. Chem. Indust. Chem. Engin.
Quart. 2015; 21: 331-341.
46. Barve VH, Hiremath SN, Pattan SR, Pal SC.
Phytochemical and pharmacological evaluation of
Hibiscus mutabilis leaves. J. Chem. Pharm. Res.
2010; 2: 300-309.
47. Wang J, Li X, Gao L, Wang X. In vitro anti-
inflammatory mechanism of folium Hibisci mutabilis
leaves ethanol extracts. Afr. J. Tradit. Complem.
Altern. Med. 2014; 11: 127-130.
48. Ghogare PB, Bhalke RD, Girme AS, Nirmal SA,
Jadhav RS, Tambe VD. Analgesic activity of bark of
Hibiscus mutabilis. Dhaka Univ. J. Pharm. Sci. 2007;
6: 55-57.
49. Mandal SC, Pal SC, Raut DN. Hepatoprotective effect
of standardized antioxidant phenolic fractions of
Hibiscus mutabilis Linn. Der Pharmacia Sinica 2014;
5: 46-51.
50. Raut DN, Patil TB, Chaudhari SR, Pal SC, Mandal
SC. Antimitotic effect of ethanol fraction of Hibiscus
mutabilis leaf and flowers. Res. Pharm. 2014; 4: 16-
18.
51. Lam SK, Ng TB. Novel galactonic acid-binding
hexameric lectin from Hibiscus mutabilis seeds with
antiproliferative and potent HIV-1 reverse
transcriptase inhibitory activities. Acta Biochim. Pol.
2009; 56: 649-654.
52. Saini P, Gayen P, Nayak A, Kumar D, Mukherjee N,
Pal BC, Babu SPS. Effect of ferulic acid from
Hibiscus mutabilis on filarial parasite Setaria cervi:
Molecular and biochemical approaches. Parasitol. Int.
2012; 61: 520-531.
53. Kumar D, Kumar H, Vedasiromoni JR, Pal BC. Bio-
assay guided isolation of α-glucosidase inhibitory
constituents from Hibiscus mutabilis leaves.
Phytochem. Anal. 2012; 23: 421-425.
54. Gogoi B, Chatterjee P, Mukherjee S, Buragohain AK,
Bhattacharya S, Dasgupta S. A polyphenol rescues
lipid induced insulin resistance in skeletal muscle
cells and adipocytes. Biochem. Biophy. Res. Commun.
2014; 452: 382-388.
55. Tambe V, Bhambar R. Investigation of analgesic and
anti-inflammatory activity for leaves of Hibiscus
cannabinus Linn. Int. J. Pharm. Drug Anal. 2014; 2:
748-753.
56. Kumar T, Udhayakumar E, Sekar M, Senthil M,
Sundarrajan T. Antidiabetic activity of methanolic
extract of Hibiscus cannabinus in streptozotocin
induced diabetic rats. Int. J. Pharm. Biol. Sci. 2011; 2:
125-130.
57. Tomar V, Kannojia P, Jain KN, Dubey KS. Anti-
nociceptive and anti-inflammatory activity of leaves
of Hibiscus rosa-sinensis. Int. J. Res. Ayurv. Pharm.
2010; 1: 201-205.
58. Raduan SZ, Abdul Aziz MWH, Roslida AH, Zakaria
ZA, Zuraini A, Hakim MN. Anti-inflammatory effects
of Hibiscus rosa-sinensis L. and Hibiscus rosa-
sinensis var. alba ethanol extracts. Int. J. Pharm.
Pharm. Sci. 2013; 5: 754-762.
59. Sawarkar A, Jangde CR, Thakre PD, Kadoo R, Shelu
S. Analgesic activity of Hibiscus rosa-sinensis Linn.
in rat. Vet. World 2009; 2: 353-354.
60. Birari RB, Jalapure SS, Changrani SR, Shid SL, Tote
MV, Habade BM. Anti-inflammatory, analgesic and
antipyretic effect of Hibiscus rosa-sinensis flower.
PharmacologyOnline 2009; 3: 737-747.
61. Bhaskar A, Vidhya VG. Hypoglycemic and
hypolipidemic activity of Hibiscus rosa-sinensis Linn
on streptozotocin–induced diabetic rats. Int. J. Diabet.
Dev. Coun. 2012; 32: 214-218.
62. Sachdewa A, Khemani, LD. Effect of Hibiscus rosa-
sinensis Linn. ethanol flower extract on blood glucose
and lipid profile in streptozotocin induced diabetes in
rats. J. Ethnopharmacol. 2003; 89: 61-66.
63. Meraiyebu AB, Olaniyan OT, Eneze C, Anjorin YD,
Dare JB. Anti-inflammatory activity of methanolic
extract of Hibiscus sabdariffa on carrageenan induced
inflammation in wistar rat. Int. J. Pharm. Sci. Invent.
2013; 2: 22-24.
64. Ali SAE, Mohamed AH, Mohammed GEE. Fatty acid
composition, anti-inflammatory and analgesic
activities of Hibiscus sabdariffa Linn. seeds. J. Adv.
Vet. Anim. Res. 2014; 1: 50-57.
65. Sogo T, Terahara T, Hisanaga A, Kumamoto T,
Yamashiro T, Wu S, Sakao K, Hou DX. Anti-
inflammatory activity and molecular mechanism of
delphinidin 3-sambubioside, a Hibiscus anthocyanin.
Biofactors 2015; 41: 58-65.
66. Farombi EO, Ige OO. Hypolipidemic and antioxidant
effects of ethanolic extract from dried calyx of
Hibiscus sabdariffa in alloxan‐induced diabetic rats.
Fundam. Clin. Pharmacol. 2007; 21: 601-609.
67. Peng CH, Chyau CC, Chan KC, Chan TH, Wang CJ,
Huang CN. Hibiscus sabdariffa polyphenolic extract
inhibits hyperglycemia, hyperlipidemia, and
glycation-oxidative stress while improving insulin
resistance. J. Agric. Food Chem. 2011; 59: 9901-
9909.
68. Pal S, Sarkar J, Bhattacharya S, Biswas M. Thin layer
chromatographic studies and assessment of anti-
inflammatory effect of Hibiscus schizopetalus leaf
extracts in rats. PharmacologyOnline 2011; 2: 1431-
1436.
69. Zahid H, Rizwani GH, Shareef H, Ahmed M, Hina B.
Analgesic and antipyretic activities of Hibiscus
schizopetalus (Mast.) Hook. Int. J. Pharm. Pharm.
Sci. 2012; 4: 218-221.
70. Zahid H, Rizwani GH, Shareef H, Khursheed R,
Huma A, Hasan SM. Antihyperglycemic and
hypolipidemic effects of Hibiscus schizopetalus
(Mast) Hook in alloxan-induced diabetic rats. Pak. J.
Pharm. Sci. 2014; 27: 83-89.
Eric et al. / A Review on the…
IJPPR, Volume 8, Issue 7: July 2016 Page 1208
71. Liu SL, Deng JS, Chiu CS, Hou WC, Huang SS, Lin
WC, Liao JC, Huang GJ. Involvement of heme
oxygenase-1 participates in anti-inflammatory and
analgesic effects of aqueous extract of Hibiscus
taiwanensis. Evid-based Complem. Altern. Med. 2012;
Article ID 132859: 13 pp.
72. Huang CH, Chen MF, Chung HH, Cheng JT.
Antihyperglycemic effect of syringaldehyde in
streptozotocin-induced diabetic rats. J. Nat. Prod.
2012; 75: 1465-1468.
73. Huang CH, Tsai SM, Chen YR, Wu MY, Cheng JT.
Dietary Hibiscus taiwanensis exerts hypoglycemic in
streptozotocin-induced diabetic rats. Int. J. Biosci.
Biochem. Bioinform. 2013; 3: 310-313.
74. Wang LY, Chung HH, Cheng JT Decrease of plasma
glucose by Hibiscus taiwanensis in type 1-like
diabetic rats. Evid-based Complem. Altern. Med.
2013; Article ID 356705: 7 pp.
75. Kuo SC, Chung HH, Huang CH, Cheng JT. Decrease
of hyperglycemia by syringaldehyde in diabetic rats.
Horm. Metab. Res. 2014; 46: 8-13.
76. Kao ES, Hsu JD, Wang CJ, Yang SH, Cheng SY, Lee
HJ. Polyphenols Extracted from Hibiscus sabdariffa
L. Inhibited lipopolysaccharide-induced inflammation
by improving antioxidative conditions and regulating
cyclooxygenase-2 expression. Biosci. Biotechnol.
Biochem. 2009; 73: 385-390.
77. Pan MH, Chiou YS, Tsai ML, Ho CH. Anti-
inflammatory activity of traditional Chinese medicinal
herbs. J. Tradit. Complem. Med. 2011; 1: 8-24.
78. Yu S, Xu L, Wei PK, Qin ZF, Li J, Peng HD. Study
on analgesic effect of traditional Chinese medicine.
Chin. J. Integr. Med. 2008; 14: 151-156.
79. Tong XL, Dong L, Chen L, Zhen Z. Treatment of
diabetes using traditional Chinese medicine: Past,
present and future. Am. J. Chin. Med. 2012; 40: 877-
886.
