Sauropus androgynus Leaves for Health Benefits: Hype and the Science

Abstract

Sauropus androgynus (SA) is a medicinal plant with high antioxidant potential. The leaves of this plant have been traditionally used to treat certain diseases, for weight loss, and as vegetable dishes. SA leaves contain an adequate amount of macronutrients and having most of the micronutrients. The micronutrients are phenolic compounds, carotenoids, antioxidant vitamins, and minerals. SA leaves also contain most of the essential minerals, including sodium, potassium, calcium, phosphorus, iron, magnesium, copper, zinc, manganese, and cobalt. Fresh leaves of SA typically consist of 70%-90% moisture, 3%-8% protein, 1%-4% fat, 1%-2% fiber, and about 2% ash. The other percentage of the leaves is carbohydrate. In this review, the types and amounts of phenolic compounds, carotenoids, antioxidant vitamins, and minerals are presented. Antinutrients and heavy metals detected in SA leaves are also revealed. These compounds could have adverse health effects, such as heavy metal toxicity and induce lung injury. Bronchiolitis obliterans and obstructive ventilatory impairment of the patients are known to be caused by ingestion of uncooked or fresh SA leaves. SA leaves are the staple food in some of the developing nations that provide essential nutrients to the poor people. It also helps to maintain good health of these people. However, fresh consumption and over-consumption of SA leaves are not advisable. It may cause toxicity or lung injury. The antioxidative components of SA leaves have scientifically shown a vast health benefit to the human being, from test tubes to in vivo studies. However, extra precaution should be taken for minimizing the adverse health effect of intake of fresh SA leaves.

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The Natural Products Journal, 2015, 5, 115-123 115
Sauropus androgynus Leaves for Health Benefits: Hype and the Science
Hock Eng Khooa,b, Azrina Azlana,b,* and Amin Ismaila,b
aDepartment of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra
Malaysia, UPM Serdang, 43400 Selangor, Malaysia; bResearch Centre of Excellence, Nutrition and
Non-Communicable Diseases, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia,
43400 UPM Serdang, Selangor, Malaysia
Abstract: Sauropus androgynus (SA) is a medicinal plant with high antioxidant potential. The leaves
of this plant have been traditionally used to treat certain diseases, for weight loss, and as vegetable
dishes. SA leaves contain an adequate amount of macronutrients and having most of the
micronutrients. The micronutrients are phenolic compounds, carotenoids, antioxidant vitamins, and
minerals. SA leaves also contain most of the essential minerals, including sodium, potassium, calcium, phosphorus, iron,
magnesium, copper, zinc, manganese, and cobalt. Fresh leaves of SA typically consist of 70%-90% moisture, 3%-8%
protein, 1%-4% fat, 1%-2% fiber, and about 2% ash. The other percentage of the leaves is carbohydrate. In this review,
the types and amounts of phenolic compounds, carotenoids, antioxidant vitamins, and minerals are presented.
Antinutrients and heavy metals detected in SA leaves are also revealed. These compounds could have adverse health
effects, such as heavy metal toxicity and induce lung injury. Bronchiolitis obliterans and obstructive ventilatory
impairment of the patients are known to be caused by ingestion of uncooked or fresh SA leaves. SA leaves are the staple
food in some of the developing nations that provide essential nutrients to the poor people. It also helps to maintain good
health of these people. However, fresh consumption and over-consumption of SA leaves are not advisable. It may cause
toxicity or lung injury. The antioxidative components of SA leaves have scientifically shown a vast health benefit to the
human being, from test tubes to in vivo studies. However, extra precaution should be taken for minimizing the adverse
health effect of intake of fresh SA leaves.
Keywords: Antioxidan t, health benefit, intoxicant, leaves, nutrient, Sauropus androgynus.
INTRODUCTION
Sauropus androgynus (SA), also called star gooseberry,
is a tropical shrub grown as a leafy vegetable. It is from
Euphorbiaceae family. In Malaysia, it is named as cekor
manis or katuk. The Indian, Indonesian, and Thai names of
SA are Ch akrmani, Katu, and Phak Wan Ban, respectively.
The plant is known to be introduced from Malaya to India
[1]. The tree of SA can grow up to 3 m in height, and the
leaves are oblong in shape. The leaves are typically 2-6 cm
long and 1-3 cm wide, the top and bottom of the leaves are
dark green and lighter green, respectively.
SA leaves are commonly known as sweet leaves due to
the sweet taste of the leaves after cooking. The leaves are a
typical Indian vegetable dish. The physicochemical
properties of SA leaves have been reported by Christi [2].
The leaves contained 4.28% total ash, 0.81% acid insoluble
ash, 1.24% water insoluble ash, and 3.42% sulphated ash; the
solvent extractable yields were 24.1% for methanol, 9.67%
for chloroform, 17.4% for benzene, 13.3% for petroleum
ether, and 20.6% for water. Besides that, the swelling factor
of the leaf powder was 9 ml.
*Address correspondence to this author at the Department of Nutrition and
Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia,
UPM Serdang, 43400 Selangor, Malaysia; Tel/Fax: +603-8947-2466;
E-mail: azrinaaz@upm.edu.my
Tradition ally, the leaves of SA are commonly used for
treating genitor-urinary diseases, cardiovascular diseases and
some other diseases [3]. In Indonesia, SA leaves have been
used as one of the ingredients for jamu. Jamu is traditionally
used to restore uterus and abdomen to the original size after
giving birth and for relieving fatigue [4]. SA leaves have also
been used to reduce body weight and to improve vision
according to the studies performed in Taiwan and Southeast
Asia [5]. Besides, the leaves of SA have been traditionally
used in India for good vision and skin problems [6]. Until
now, there is no documentation of clinical trial on the
prevention and treatment of these diseases using SA leaves.
Conversely, eating the leaves in a large amount can cause
nausea, dizziness, vomiting, diplopia, sedation, weakness,
and uncontrolled eye movements [7]. On the other hand, the
protective effect of SA leaves could be due to the
antioxidative compounds in the leaves [2].
Green leafy vegetables contain a high amount of
carotenoids, vitamins, and minerals [7]. Besides these
nutrients, other bioactives are mainly lignan and
megastigmane glycosides [8]. Carotenoid and polyphenol are
also the typical antioxidants in green leafy vegetables. Beta-
carotene is the major carotenoid in plant. However, some of
the green leafy vegetables have a high amount of
xanthophylls, such as lutein and zeaxanthin. The leaves of
SA contain significantly higher total flavonoid content than
the other studied leafy vegetables except the leaves of
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116 The Natural Products Journal, 2015, Vol. 5, No. 2 Khoo et al.
Calamus scipronum (Semambu leaves) [9]. Among the
flavonoids determined in the study, quercetin and
kaempferol were the major flavonoids detected in SA leaves.
SA leaves possess a high total phenolic content and
antioxidant activities. The total phenolic content of SA
leaves of Indonesian origin was not significantly lower than
the total phenolic content of the leaves of Cosmos caudatus
(Ulam Raja leaves) [10]. Based on the electron transfer
reaction assays, SA leaves contained higher antioxidant
activities than many other leafy vegetables of Indonesian
origin. Due to the beneficial effect of SA leaves in reducing
body weight and possessing antinematodal activity, the
leaves should have containing bioactive antioxidants, such as
carotenoids, flavonoids, and other phytochemicals. These
phytochemicals can reduce oxidative stress, thus reduce the
risk of some chronic diseases.
Although no scientific evidence has proven the protective
effect of SA leaves against certain chronic diseases, the
search for a prevention of these diseases using SA leaves is
still ongoing. Based on the scientific evidences, the possible
health benefits of SA leaves are discussed in this review.
NUTRITIONAL COMPOSITIONS
Macronutrients
The leaf of SA is a nutritious food. Nutrients of the leaf
compliment with other food for an individual to obtain
enough macronutrients for survival. The proximate
compositions or macronutrient contents of SA leaves are
depicted in Table 1. SA leaves have moisture content
ranging between 69.9% and 89.9%, and the protein contents
of both dry and fresh samples of SA are in the range between
4.2% and 29.15%. Some of the SA leaf samples have high
fiber content, and the carbohydrate content of SA leaves
have not been reported by some of the previous studies.
Vitamins and Minerals
Vitamin and mineral contents of SA leaves have been
determined previously using chromatographic and
spectrophotometric methods. The vitamin and mineral
contents of SA leaves are depicted in Tables 2 and 3,
respectively. The major vitamins for the leaves are vitamins
A and C. Vitamin A of SA leaves is probably due to the pro-
Table 1. Nutritional composition of Sauropus androgynus (SA) leaves.
Composition India
[7]
India
[11]
India*
[6]
Thailand*
[12]
Thailand*
[14]
Indonesia
[13]
Indonesia*
[10, 15]
Vietnam
[16]
Malaysia
[17]
Energy (kcal) ˗ 28.0 ˗ 40.4 317 401.4 ˗ ˗ 100.5
Moisture (%) 69.9 88.0 85.4 88.5 89.9 - 82.9g 86.9 79.4
Protein (%) 7.4 3.4 5.3 4.2 15.8 29.2 8.31h ˗ 7.6
Carbohydrate (%) ˗ 0.5 ˗ 3.9 54.5 - ˗ ˗ 6.9
Fat (%) 1.1 1.4 0.6 0.9 4.0 4.6 ˗ ˗ 1.8
Fiber (%) 1.8 1.7 1.8 1.2 36.0 8.2 ˗ ˗ 1.9
Ash (%) ˗ - 5.3 1.4 12.9 12.1 - 1.4 2.0
Footnote: * indicates the data have been reported in the review article by Petrus [18]. For the samples obtained from Thailand [14] and Indonesia [13]; the compositions are
expressed as % dry weight (DW) excluding the moisture content.
Table 2. Vitamin s content of Sauropus androgynus leaves.
Place of Origin Vitamin A
(β-carotene Equivalent)
Thiamine
(Vitamin B1)
Riboflav in
(Vitamin B2)
Vitamin C
(Ascorbic Acid)
India [7] 5.6 ± 0.2 0.5 ± 0.03 0.21 ± 0.01 244 ± 15
India [20] - - - 22.0
India* [6] 19.4 ± 0.6 - - 314.3 ± 1.8
Thailand* [14] - - - 56.1
Thailand [21] 4.4 ± 0.1 - - 114.9 ± 0.6
Indonesia* [15] - - - 190.83 ± 0.82
Vietnam [16] 5.3 - - -
China [22] - - - 31.25
Footnote: * indicates the data have been reported in the review article by Petrus [18]. Values are expressed as mg/100 g of the leaves; fresh weigh (FW) basis [7]; FW basis [20]; FW
basis-µg/100 ml [6]; DW basis-89.9% moisture [14]; FW basis [21]; FW basis [15]; FW basis [16]; FW basis [22].

Health Benefits of Sauropus androgynus The Natural Products Journal, 2015, Vol. 5, No. 2 117
vitamin activity of carotenoid, such as β -carotene. The SA
plant, including the leaf, has vitamin C content of 22-244
mg/100 g fresh weight (FW). The wide range of vitamin C
in SA plant (including leaves) could be due to several
reasons. The typical reasons are d ifferent parts of SA
plant and methods of analysis used. Besides these vitamins,
vitamins B1 and B2 contents quantified in the SA leaves are
0.5 and 0.21 mg/100 g FW, respectively. The amounts of
these B vitamins are considered higher than many other leafy
vegetables. The SA leaves also contain α-tocopherol, which
is 42.68 ± 0.12 mg/100 g edible portion [11].
Essential minerals, as the most importan t elements in the
human body, are also abundantly found in SA leaves. As
shown in Table 3, the minerals detected in SA leaves are
sodium (Na), potassium (K), calcium (Ca), phosphorus (P),
iron (Fe), magnesium (Mg), zinc (Zn), manganese (Mn), and
cobalt (Co). The leaves of SA also contain vanadium (Va),
selenium (Se), and chromium (Cr) [18]. Some of these
minerals from the leaves can be toxic to the human body if
taken in high doses. A high Ca content (771 mg/100 g FW)
was determined for the SA leaves from India as compared to
the other countries (Table 3). Besides, Indonesian SA leaves
contained a higher amount of Mg (1004.3 mg/100 g FW)
compared with the Mg content of 664.9 mg/100 g dry weight
(DW) that determined by the Indian scientist. The SA plant
from Indonesia has about 1% of Mg from the edible portion.
The extremely high Mg content in SA plant could be due
to the soil contaminated with magnesium or sample
contamination during sample preparation and analysis.
In nature, a great variation in minerals content is found
for SA planted in different geographical locations. Soil
contamination and other human activities could contribute to
the greater variation in the mineral composition of SA
leaves. However, these essential minerals are needed for the
human body through consumption of the edible portion of
the plant or leaves.
The minerals attribute to dietary intake from the leaves of
SA were zinc (4.3 mg/kg FW) and iron (14.8 mg/kg FW),
which based on a cross-sectional study among the female
populations of two farming villages in the Red River Delta,
Vietnam [19]. The study showed that consumption of
SA leaves helped to improve the nutritional status of the
poor people in Vietnam, especially when consuming a
mixture of fresh leaves of SA, amaranth, mustard green, and
spinach.
BIOACTIVE ANTIOXIDANTS
The total phenolic content (TPC) of SA leaves has been
well determined and reported in a review article by Petrus
[18]. Based on the previous studies, TPCs of SA leaves were
11.5 mg GAE/g DW [14], 11.51 ± 2.9 mg GAE/g DW [5],
20 mg GAE/g DW [23], 19 mg GAE/g FW [24], 1.49 mg
GAE/g FW [10], and 1.38 mg GAE/g FW [15]. Besides,
TPC of the methanolic extract of SA leaves from India was
9.82% (w/w) [25]. It shows that the leaves of SA have high
total phenolics. However, the total flavonoid content in the
leaves of C. scipronum was 2.6 times higher than the total
flavonoid content of the leaves of SA. Morever, the TPC of
SA leaves from Thailand was 48.42 ± 2.13 mg GAE/100 g
FW [12]. The amounts of total flavonoids and potential
flavonoids are shown in Table 4. Total flavonoid content of
SA leaves has been determined as 10.4 mg rutin equivalent
(RuE)/g DW [14] and 15.3 mg RuE/g FW [24]. The total
flavonoids reported by Miean and Mohamed [9] (78.5 mg
/100 g DW) and by Andarwulan et al. [10, 15] (143 mg/100
g FW) are the total amounts of individual flavonoids
determined. Besides, total anthocyanin content of SA leaves
has been reported as 82.8 ± 1.1 mg cyanidin-3-glucoside/100
g DW [6] or 1.53 mg/100 g FW [15].
Carotenoids have been detected in SA leaves. The hexane
extract of SA leaves contained 1.63 ± 0.02 mg/100 g FW of
β-carotene, and the total carotenoid content was 5.15 ± 0.07
Table 3. Minerals content of Sauropus androgynus (SA) leaves.
Composition India
[7]
India*
[20]
India*
[6]
Thailand*
[12]
Thailand*
[14]
Indonesia
[13]
Vietnam
[16]
Na - - 306.3 ± 52.8 396.0 - - -
K - - 45.7 ± 1.5 - - - -
Ca 771 ± 11 313.0 84.4 ± 8.1 70.5 118.8 249.9 158
P 543 ± 18 - 61.2 ± 3.5 128.2 - 300 -
Fe 8.8 ± 0.3 10.09 212.5 ± 20.8 0.9 13.5 36.4 1.6
Mg - - 664.9 ± 38.1 - - 1004.3 -
Cu
Zn - - 15.9 ± 6.6 0.9 - 20.2 1.0
Mn - - 25.6 ± 5.8 - - - -
Co - - 1.6 ± 0.1 - - - -
Footnote: * indicates the data have been reported in the review article by Petrus [18]. Values are expressed as mg/100 g of the leaves; FW basis [7]; FW basis [20] ; DW basis-85.4%
moisture [6]; FW basis [12]; DW basis-89.9% moisture [14]; FW basis [13]; FW basis [16].

118 The Natural Products Journal, 2015, Vol. 5, No. 2 Khoo et al.
mg β -carotene equivalent/100 g FW [15]. The leaves also
have all-trans-α- and β-carotene contents of 1.34 and 10.01
mg/100 g FW, respectively [26]. Also, the neoxanthin and
violaxanthin contents of SA leaves were 9.33 ± 0.45 and
11.76 ± 1.51 mg/100 g DW, respectively [27]. Besides
carotene, the leaves of SA contained 19.5 ± 0.8 mg lutein
and 8.5 ± 0.7 mg zeaxanthin in 100 g FW [28]. The total
carotene content of SA leaves was 5.6 ± 0.22 mg/100 g fresh
leaves. Some of the data have been revealed by Petrus [18]
in a review article. Other than major bioactives, tannic acid
was not detected in the leaves of SA [16]. Conversely, Singh
et al. [6] reported that 88.7 ± 1.1 mg tannin (tannic acid
equivalent) was detected in 100 g fresh leaves of SA, and the
leaves also have chlorophyll content of 45.6 ± 0.7 µg/100 ml
FW. Besides, hexamositol phosphate (284.0 mmol/100 g
FW) was also detected in SA leaves obtained from Vietnam.
The shoot of SA that containing total flavonoids has been
analyzed using NMR. The result showed that four lignan
glycosides, a megastigmane glucoside, guanosine, and
corchoionoside were identified in the aerial part of SA
[8]. The lignan glycosides were (−)-isolariciresinol
3α-O-β-apiofuranosyl-(1→2)-O-β-glucopyranoside, (+)-
isolariciresinol 3α-O-β-glucopyranoside, (−)-isolariciresinol
3α-O-β-glucopyranoside, and (+)-syringaresinol di-O-β-
glucopyranoside; the megastigmane was sauroposide.
Besides lignan, bioactive flavonoids are also found in the
leaves of SA. A previous study reported that 3-O-β-D-
glucosyl-(1→6)-β-D-glucosyl-kaempferol was isolated from
the SA plant [29].
Although no previous study determines the antioxidant
activities of these lignan glycosides, lignan glycosides
isolated from the methanolic extract of Saraca asoca bark
have moderate to high antioxidant activities that based on
EC50 values of DPPH radical scavenging assay [30]. Based
on the reported EC50 values, some of the identified lignan
glycosides have antioxidant activity comparable with
flavonoids. Besides, six bioactives have also been identified
in the aerial part of SA [31]. These bioactives were three
nucleosides, two flavonol diosides, and one flavonol trioside,
where kaempferol was the major flavonoid in the leaves of
SA. The shoot of SA has 53.8 mg/100 g kaempferol, but
quercetin, isorhamnetin, luteolin, and apigen in were below
the detection limit [32].
Another study revealed that the aqueous extracts of SA
leaves were tested positive for triterpenoids using Salkowski
test [33]. The volatile components of the essential oil from
SA leaves have been determined by Lin et al. [34]. The
results showed that the major components of the essential oil
were carvacrol methyl ether, thymol, and butylated
hydroxytoluene. Other phytochemicals detected in SA leaves
using GCMS were 1,14-tetradecanediol, 1-octadecyne,
1-hexadecyne, decanoic acid, ethyl ester, phytol, pyrene,
napthalenone, azulene, and squalene [35].
POTENTIAL HEALTH BENEFITS
Wild vegetables are rich in micronutrients and
phytochemicals. These wild vegetables contain potent
antioxidants. As shown in Table 4, previous literature
reported that the leaves of SA have a high level of bioactive
antioxidants. An increased consumption of wild vegetables
such as SA leaves, significantly contributed to the high
overall micronutrient intakes among the rural women in
Vietnam [36]. Among the phytochemicals, polyphenols are
the well-known bioactives in prevention and treatment of
various diseases. Besides phenolic compounds, guanosine is
a potential bioactive in SA leaves that displayed antioxidant
activity and protective effect against oxidative damage [37].
Antioxidative Effects
Total antioxidant capacity (TAC) of methanolic extract
of SA leaves has been determined and expressed as ascorbic
acid equivalent. The TAC of SA leaves obtained from India
was significantly higher than the TAC of the leaves o f
Trigonella foenum-graecum, Centella asiatica, and Pisonia
alba at extract concentrations of higher than 100 µg/ml [24].
It could be due to the leaves contained a high amount (>200
mg/100 g FW) of ascorbic acid (Table 2). Besides that, the
antioxidant capacity of Thai’s SA leaves was 17.62 ± 1.93
mg vitamin C equivalent/100 g FW [12]. Similarly, the
results obtained from DPPH scavenging assay showed the
highest scavenging for the methanolic extract of SA leaves,
but not for ABTS and lipid peroxidation assays. The high
scavenging activity of SA leaf extract could be due to the
highest levels of total flavonoids and total phenolics
determined among the methanolic extracts of four Indian
leafy vegetables. Besides, the methanolic extract of SA
leaves has TAC of 85.6 ± 1.02%, where the EC50 value of
TAC was 201.1 µg rutin equivalent/100 g DW [6].
Alternatively, antioxidant activities of SA leaves as
assessed using DPPH and FRAP assays were 130 and 190
µM Trolox equivalent/g DW, respectively, whereas the
cupric ion chelating activity of the leaves was 79% of cupric
ions chelated [23]. The antioxidant activities of the leaves
were also significantly higher than many other plants
studied. The high antioxidant activity of SA leaves is known
to correlate strongly with TPC, where the DPPH and FRAP
assays are based on the electron transfer reaction pathway.
Conversely, the high antioxidant activities of SA leaf extract
could be due to the present of protein components in the
extracts, especially aqueous extracts of SA leaves [38]. The
Table 4. Flavonoids content in the leaves of Sauropus
androgynus.
Flavonoids Malaysia
[9]
Indonesia
[10, 15]
Apigenin ND <0.03
Kaempferol 32.4 ± 0.01 138.0 ± 5.8
Luteolin ND <0.006
Myricetin ND <0.00002
Quercetin 46.1 ± 0.01 4.5 ± 0.22
Total flavonoids 78.5 143.0 ± 6.0
Footnote: The results are expressed as mg/100 g DW [9] and mg/100 g FW (82.9%
moisture) [10, 15]. ND: not detected (below limit of detection).

Health Benefits of Sauropus androgynus The Natural Products Journal, 2015, Vol. 5, No. 2 119
antioxidant activity of SA leaves also has been reported as
EC50 of 1.43 µg/ml that based on DPPH radical scavenging
assay [14].
As assessed using several antioxidant methods, the
methanolic extract of SA leaves has moderate antioxidant
capacities compared with the other medicinal plants in India
[25]. These antioxidant methods used were ABTS, DPPH,
lipid peroxidation, H2O2, p-NDA, and nitric oxide assays,
where the methanolic extracts have EC50 values (µg/ml) of
12.58, 341.00, 228.75, 370.00, >1000, and >700,
respectively. The result also showed that the total antioxidant
capacity of SA leaf extract that analyzed using ammonium
molybdate method was 2.41 µM ascorbic acid equivalent/g
extract. Besides, the DPPH radical scavenging activity,
reducing power, and metal chelating capacity of SA leaf
extracts have been determined previously [39]. The SA
leaves were extracted using four types of extraction solvents,
such as petroleum benzene, chloroform, methanol, and
water. Among the extracts, petroleum benzene has the lowest
EC50 value (36.25 µg/ml) based on DPPH assay. As
compared with water extract of SA leaves, the petroleum
benzene extract has 8.5 times lower EC50 value than the
water extract. The petroleum benzene extract of SA leaves
also has the highest reducing power determined using
ferricyanide method (1.53 unit of absorbance reading
measured at 700 nm) compared with the lowest absorbance
reading at 0.23 unit for chloroform extract. Besides, the
chelating capacity of ferrous ion (70.7%) for the chloroform
extract of SA leaves was the highest; however the water
extract of SA leaves has the lowest capacity (48.1%).
The results obtained from SA leaf extract were also
compared with the other vegetables (curry leaves, celeries,
sweet potato leaves, winged beans, and garlic chives).
Moreover, the EC50 values (95, 135, and 63 µg/ml) of SA leaf
extract for ferricyanide reducing power, DPPH, and hydrogen
peroxide scavenging assays, respectively, were higher than
the EC50 values of typical antioxidants, ascorbic acid, and
epicatechin [2]. Also, the antiradical activity (1/EC50) of SA
leaves was 0.7 [40]. The 1/EC50 value is higher than many
other Thai plants. Based on all the reported data, therefore,
SA leaves are considered as the vegetable with moderately
high antioxidant activities.
Weight Loss
A flavonoid isolated from SA plant has been shown to
prevent weight gain in laboratory rats fed with a high-fat
diet. The rats supplemented with 60 mg/kg body weight
(BW) of the flavonoid [3-O-β-D-glucosyl-(1→6)-β-D-
glucosyl-kaempferol] isolated from SA plant significantly
reduced food intake by 15%, and significantly reduced serum
free triglyceride level without obvious histopathological
changes [29].
Previously, the fresh leaves of SA or juice from the
leaves have been used by young and middle-aged women for
the perceived weight loss effect. On the contrary, there are
cases reported in some countries in Asia regarding the
adverse effect of consuming SA leaves [41]. The cases were
related to “bronchiolitis interstitial pneumonitis”. Based on a
study reported by Hung et al. [42], ten healthy women who
have confirmed lung distress self-reported that they
consumed SA leaves (juice, extract, or cooked dishes) for
weight loss. The respiratory distress could probably due to
the ingestion of fresh SA leaves.
Alkaloids, glycosides, and saponin have been detected in
fresh leaves of most plants. These compounds are somehow
toxic [43]. Although papaverine is one of the main bioactives
in SA leaves, some researchers hypothesized that it can
cause bronchiolitis. However, an animal study in Taiwan
proven that ingestion of SA leaves and papaverine do not
cause bronchiolitis [44]. In fact, papaverine is an
antispasmodic drug. For that reason, consumption of fresh
SA leaves or freshly blended juice of SA leaves is not
recommended for weight loss. Cooking or blanching of SA
leaves for consumption as vegetable dishes will somehow
work better.
Antimicrobial
SA leaves can inhibit the growth of both gram positive
and gram negative bacteria. Paul and Anto [45] reported that
the ethanolic extract of SA leaves showed higher inhibitory
effects against Klebsiella pneumonia (gram negative) and
Staphylococcus aureus (gram positive) than the aqueous
extract. Besides the inhibitory effects of these bacteria, the
methanolic extract of SA leaves has the highest inhibitory
effect against Pseudomonas aeruginosa, S. aureus, Proteus
vulgaris, and Bacillus subtilis compared with the methanolic
extracts of SA stems and roots, excep t for Eschelicia coli
[34].
Conversely, the aqueous extract of SA leaves has weaker
microbial inhibition than the methanolic extract. The
methanol, ethanol, and aqueous extracts of SA were also
tested for antimicrobial activities. Based on the results
obtained from agar diffusion assays, the methanolic extract
has higher inhibition activity than the aqueous extract of SA
leaves against six bacterial strains (gram positive and gram
negative bacteria) [46]. However, the inhibition zones of all
the extracts were lesser than the standard streptomycin used.
The results also showed that the SA leaf extracts have 41%
to 79% of inhibition in relation to streptomycin.
Anti-inflammatory and Wound Healing
SA leaves possess an anti-inflammatory effect. The
extracts of SA leaves at concentrations of 200 and 400
mg/kg BW have shown significant reduction (>50%) in the
carrageenan-induced edema of rat paw in 1 hour compared
with the drug (papaverine) used [47]. Christi [2] also
reported a significant reduction in edema volumes for the
rats fed with 250 mg SA extracts or 1 ml of juice per kg BW
compared with the control (0.75% carboxymethyl cellulose).
Addition of lipopolysaccharide to macrophages resulted in a
reduction in the levels of selected inflammatory markers,
such as cyclooxygenase-2 and its intermediate products
(prostaglandin E2 and nitric oxide) in a dose-dependent
manner (20-200 µg/ml) [48].
Lipopolysaccharide is known to induce oxidative stress
and increase production of these inflammatory markers in
RAW 264.7 cells [49]. Significant reductions in the
inflammatory markers show the effectiveness of SA leaf

120 The Natural Products Journal, 2015, Vol. 5, No. 2 Khoo et al.
extract in reducing oxidative stress, thus exhibit the anti-
inflammatory effect. Besides, the extract also suppressed
the gene of cytokine-inducible nitric oxide synthase, where
it is highly expressed in the lipopolysaccharide-induced
macrophages.
Wound healing effect of SA leaves has been determined
by Bhaskar and Ramesh [50]. The authors reported that the
SA leaf extract significantly promoted wound healing
activity in both male and female rat models. The results
showed that 5% SA extract was significantly augmented
wound contraction, re-epithelialized, and increased wound
breaking strength by applying topically once a day onto the
wound. Besides, a histological observation also showed
abundant collagenation, fibroblast, and lesser macrophages
in the wound tissue of the Wistar rats treated with SA extract
compared with positive and negative controls. In addition,
the SA extract has been studied for its anticonvulsant activity
[51].
Other Health Benefits
Although no previous literature has reported the potential
cardioprotective effect of SA leaves using in vivo model, a
study has demonstrated that fermented SA leaves were
effectively reduced 19.32% cholesterol content in chicken
meat compared to control (ration without addition of
fermented SA leaves) [52]. The experimen tal chicken were
fed with fermented SA leaves for eight weeks before
slaughtered. The study hypothesized that the cholesterol-
reducing effect in the chicken was mainly contributed by the
β-carotene content in SA leaves. The effect could be due to
the inhibition of enzyme HMG-CoA reductase activity by β-
carotene in the leaves.
Consumption of average cumulative dosage of SA leaves
(2.67 ± 1.89 kg, range 0.4-8.0 kg) was shown to significantly
lower Tiffeneau-Pinelli index (FEV1/FVC ratio) of the
patients with respiratory symptoms than the patients without
the symptoms. The result showed so me improvement in the
severe impairment of alveolar permeability for the patient
with obstructive and restrictive lung disease that treated with
SA leaves [53]. Besides, the antioxidants in SA leaves could
prevent sev eral chronic diseases, such as cancer and
coronary heart disease [54]. A previous study on the
determination of alpha-tocopherol contents in 62 edible
tropical plants reported the leaves of SA have the highest
concentration (426.8 mg/kg edible portion) of alpha-
tocopherol [11]. The high alpha-tocopherol content of SA
leaves signifies a potential protective effect of SA against
several chronic diseases.
The leaf extract of SA has a strong anticancer effect. The
SA leaf extract at concentration of 200 µg/ml showed
complete inhibition (100%) of EBV (Epstein Barr virus)
activation using Raji (human Burkitt's lymphoma) cells and
without any cytotoxic effect [55]. In fact, inhibition of EBV
activation suppresses tumor promoter that can cause
development of cancer [56]. Although the SA leaf extract is
cytotoxic to cancer cell lines and Raji cells, the leaves should
not be toxic to the human body. However, a study reported
some accumulative toxicity in mice during 30 days of
feeding with SA leaves [57]. The lethal dose (LD50) of SA
leaves was >10.00 g/kg BW, and the higher dose increased
sperm abnormality in mice. Prolong intake of SA leaves
damaged the organs of the experimental mice, such as liver,
kidney, spleen, heart, lung, and testis; whereas increase dose
of SA leaves could worsen the damage to these organs.
Therefore, a long-term consumption of SA leaves is not
advisable because the toxic glycosides from the leaves could
be accumulated in the organs.
On the other hand, consumption of SA leaves could
benefit lactating women. A study reported that lactating
mice supplemented with SA leaf extracts have 2 to 26-fold
increased expression of prolactin and oxytocin genes in the
pituitary glands of the mice [58]. It shows that SA leaf
extracts helped to increase the milk production. In a human-
based study, the leaf extract of SA has been proven to
increase production of mother’s breast milk. Besides, a study
in Indonesia reported that SA leaf extract has increased
breast milk production of lactating mothers up to 50.7%
compared to placebo [59]. Another similar study proved the
benefit of consuming SA leaves for increasing production of
human breast-milk [60]. Moreover, increased consumption
of SA leaves has significantly increased the level of vitamin
A in the breast milk of breastfed mothers in a few districts of
Indonesia [61]. In addition, milk production in mammals
resulting from the consumption of SA leaves has also been
determined using several animal models.
Therefore, the benefits of consuming SA leaves are
related to the bioactive compounds in the leaves, including
carotenoids and phenolic compounds. The main bioactive in
SA leaf extract was papaverine, where a high concentration
(0.38 ± 0.04 µg/ml) of the compound has been determined in
the extracts.
SAFETY ISSUES
In general, the leaves of SA are not toxic to the human
body if consumed moderately. A study showed that the
medium lethal dose (LD50) of fresh SA leaf homogenate was
>21.5 g/kg BW of male’s NIH mice, and the LD50 value for
dried leaf powder was >20.0 g/kg BW of the mice [62]. All
mice were fed with the SA samples for 90 days. The result
for sub-chronic toxicity test showed that all the indexes and
values (lymphocytes, Th1 gene expression, and blood
biochemical parameters) were in the normal range if
supplemented with the fresh leaf homogenate. Although the
toxicity level of SA leaves is low, the leaves may contain
antinutrients and heavy metals that pose adverse health
effects to the human body.
Antinutrients and Heavy Metals
A study reported that SA leaves contained tannin (0.46
g/100 g DW) and saponin (2.84 g/100 g DW) [13]. As
mentioned in the earlier section, the leaves contained 88.68
mg tannin/100 g FW [6]. The leaves of SA also contained
oxalic acid (33.25 mg/100 g FW) as antinutrients [20]. These
chemical components are antinutrients, but they possessed
antimicrobial activities. Due to these chemical components
in SA leaves, the leaf extract is somehow toxic to NIH3T3
fibroblasts. The chemical components in the extract were
shown to induce apoptosis in the cells [5]. On the other hand,
contamination of soil with heavy metal is the main reason for
the toxic effect of SA leaves. A previous study showed that

Health Benefits of Sauropus androgynus The Natural Products Journal, 2015, Vol. 5, No. 2 121
cadmium was detected in a few SA samples, where the
contamination was originated from soil [63].
On the contrary, SA samples obtained from different
locations in Indonesia showed a variation in cell cytotoxicity
for human mesenchymal stem cells [60]. The methanolic
extract of SA sample obtained near Purwosari has the lowest
cell viability (37%). However, the sample collected from
East Java has a high percentage of cell viability (75%). The
results obtained from this study show that geographical
location is the main cause of accumulation of toxic
compounds that can reduce cell viability.
Lung Injury
An in vitro study shows that the aqueous fraction of SA
dried powder significantly elevated the inflammatory
cytokine and chemokine production in monocytic lineage
cells, significantly induced apoptosis of endothelial cells, and
enhanced intraluminal obstructive fibrosis in allogeneic
trachea allograft in the murine bronchiolitis obliterans
syndrome’s model [64]. The study also reported that
consumption of SA leaves stimulated production of TNF-α
in monocytes of healthy controls and induced a high-level
production of TNF-α from monocytes of patients who
consumed SA leaves.
Besides the in vitro studies, the outbreak of lung diseases
or bronchiolitis obliterans is known to be associated with
intake of SA leaves [65]. Several cases of obstructive
ventilatory impairment and bronchiolitis obliterans have
been found to associate with the consumption of SA leaves
in Taiwan [66] and Japan [67]. The outbreak of obstructive
ventilatory defect among 44 Taiwanese was reported by Lin
et al. [66] between August 23, 1994 and August 25, 1995.
They suffered from typical symptoms, including temporary
insomnia, poor appetite, and breathing difficulty after intake
of SA leaves for four weeks or more. Out of the 44 patients,
93.2% of them were women who consumed SA leaves as a
vegetable.
Another hospital-based case-control study that performed
in southern Taiwan between April and September 1995
revealed an outbreak of a poorly defined respiratory illness
associated with intake of SA leaves [68]. The results showed
that among the 54 cases and 54 self-referred patron controls,
several factors were reported to associate with bronchiolitis
obliterans syndrome. These included methods of food
prepared from SA leaves [uncooked juice vs. stir fried or
boiled dishes, matched OR 10.3 (95% confidence interval of
1.3-84.4)], person who prepared the SA leaves-containing
food [vendor only vs. patient only or patient plus vendor,
matched OR 2.8 (95% Cl 1.1–7.1)], total consumption of SA
leaves [>4, 500 vs. 413–2063 g, matched OR 10.0 (95% Cl
1.9–53.0)], duration of consumption of SA leaves [>45 vs.
6–24 days, matched OR 2.1 (95% Cl 1.2–3.8)], and midterm
interruption [<2 vs. 2–5 days per week, matched OR 2.6
(95% Cl 1.1–6.1)]. The study concluded that SA leaves-
containing food prepared without cooking and prepared by
the vendor were significantly associated with bronchiolitis
obliterans syndrome.
In Japan, five cases of SA-associated bronchiolitis
obliterans are reported [67]. All the patients have a severe
obstructive disturbance in pulmonary function tests and
marked variability in attenuation of lung parenchyma.
These patients were treated with corticosteroids and
bronchodilators but did not have improved symptoms.
Moreover, the obstructive ventilation detected was dose
dependent. The number of cases was higher in high-dose
group than the low-dose group, where the total doses
consumed per day for the 178 patients analyzed were A
(0-1799 g), 4/43=9.3%; B (1800-3599 g), 13/64=20.3%;
C (3600-5399 g), 14/32=43.8%; D (5400-7199 g),
5/12=41.7%; and E (≥7200 g), 13/27=48.1%; p<0.01 [69].
One of the main causes of bronchiolitis obliterans is
papaverine exposure. An animal model was designed to test
the effect of papaverine on bronchiolitis obliterans using 33
Sprague-Dawley rats via intratracheal delivery of papaverine
[70]. The results showed that at day-7 of papaverine induced to
the rats, inflammation of peribronchial was observed. The other
clinical observations were extensive denudation, destruction
of the bronchial mucosa, and increased peribronchial collagen
(all classic signs of chronic bronchiolitis obliterans). The
damage worsened after 28 days of papaverine induced to the
rats. Besides that, TGF-β and eNOS of the lung homogenates
were significantly increased. Based on the results obtained,
the study suggested that the papaverine-induced model
implicates the pulmonary process of collagen remodeling.
CONCLUSION
S. androgynus is the medicinal plant that contains a fairly
high amount of bioactive antioxidants. These antioxidants,
including phenolic compounds, carotenoids, anthocyanins,
some volatile compounds, and other phytochemicals have
high free radical scavenging activities, thus inhibit oxidative
stress. Inhibition of oxidative stress by these antioxidants can
prevent inflammation and the onset of several chronic
diseases. The bioactives from S. androgynus leaves also
possess antimicrobial and anticancer effects. These
bioactives may somehow pose adverse health effect to the
human body because some of the compounds are toxic.
Intake of fresh leaves of SA for the potential health
benefits is not advisable as the past evidences reveal several
outbreaks of bronchiolitis obliterans. Therefore, proper
preparation of the leaves is needed prior to consumption for
any purposes. Hype or scientific-based evidences for the
potential health benefits from the intake of S. androgynus
leaves? Consumers should make the right decision.
CONFLICT OF INTEREST
The authors confirm that this article content has no
conflict of interest.
ACKNOWLEDGEMENTS
Declared none.
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Received: April 02, 2015 Revised: May 28, 2015 Accepted: May 30, 2015