Gundelia rosea seed: Evaluation of biopharmaceutical potential
and bioactive composition
A. Dalar
a,⁎
, G. Zengin
b, M. Mukemre
c, A.S. Bengu
d, S.
İşler
ea
Department of Pharmaceutical Botany, Faculty of Pharmacy, Van Yuzuncu Yil University, Van, Turkey
bDepartment of Biology, Faculty of Science, Selcuk University, Konya, Turkey c
Department of Biology, Faculty of Science, Van Yuzuncu Yil University, Van, Turkey
d
Department of Medical Services and Techniques, Vocational School of Health Services, University of Bingol, Turkey
e
Department of Science and Mathematics, Faculty of Education, Van Yuzuncu Yil University, Van, Turkey
a b s t r a c t
a r t i c l e i n f o
Article history: Received 10 May 2019
Received in revised form 3 July 2019 Accepted 16 August 2019 Available online 29 August 2019 Edited by AR Ndhlala
Gundelia species are among significant key medicinal plants extensively utilized in folk medicine of Middle East-ern countries. This study focused on researching the biopharmaceutical potency and bioactive compounds of Gundelia rosea seed. Hereby, traditional knowledge-based preparing methods (infusion and decoction) and ethanol-based lyophilized extracts obtained from Gundelia rosea seeds were assessed for (i) antioxidant capaci-ties, (ii) enzyme inhibitory activicapaci-ties, (iii) HPLC-MS/MS and (iv) GC–MS studies.
Phytochemical analysis revealed that ethanol extract which primarily compromised of mainly phenolics (4-Caffeoylquinic acid and luteolin hexoside) and several fatty acids (palmitic, stearic, oleic and linoleic acids), was superior to those of infusion and decoction extracts. Antioxidant activitiesfindings revealed that ethanol extract contained a high level of total phenolics (55.3 mg Gallic acid Eq./g extract) and had high capacities of re-ducing (1683μmol Fe2+and 214.1 mg Trolox Eq./g extract for FRAP and CUPRAC respectively) and radical
scav-enging (ORAC: 2241.9μmol, DPPH: 91.7 mg, ABTS: 141.2 mg Trolox Eq./g extract) and total antioxidant (Phosphomolybdenum: 1.39 mmol Trolox Eq./g extract) properties. The suppressive abilities of the extracts against selected isolated enzymes revealed that ethanol extract had pronounced levels of inhibitory activities against AChE (4.3 mg Galanthamine Eq.), BChE (3.4 mg Galanthamine Eq.), tyrosinase (120 mg Kojic acid Eq.), amylase (0.61 mmol Acarbose Eq.), glucosidase (11.91 mmol Acarbose Eq.) and lipase (53.4μmol Orlistat Eq.) per gram extract. Findings obtained within this study confirmed the traditional utilization of Gundelia rosea and suggest its potential as a novel candidate of biopharmaceutical agents for public health problems.
© 2019 SAAB. Published by Elsevier B.V. All rights reserved.
Keywords: Gundelia rosea 4-Caffeoylquinic acid Fatty acids Biopharmaceuticals 1. Introduction
Gundelia taxa known as tumbleweed belong to Asteraceae are pe-rennial medicinal plants native to Middle Eastern countries. They have been utilized for a wide range of diseases treatment in traditional med-icine such as chest pain, heart stroke, diabetes, laxative, gastric pain,
bronchitis, inflammations, dental abscess, epilepsy and kidney stones
(Halabi et al., 2005; Jarald et al., 2008; Sarper et al., 2009; Dalar et al.,
2018). Scientific studies regards to Gundelia species such as in vitro
an-tioxidant and enzyme inhibitory (Sekeroglu et al., 2012), antitumor in
cell culture (Abu-Lafi et al., 2019), in vivo antidiabetic (Mohammadi
et al., 2018; Kadan et al., 2018) activities and phytochemical
composi-tion (Haghi et al., 2011; Sekeroglu et al., 2012; Asgari et al., 2015;
Kadan et al., 2018; Abu-Lafi et al., 2019) were principally focused on
Gundelia tournefortii and scientific data with regard to
biopharmaceuti-cal potential of other Gundelia species were limited.
In Turkey, Gundelia species have been commonly used for a wide range of utilization including medicine, food, forage, chewing gum and
coffee (Sekeroglu et al., 2012; Dalar et al., 2018). Among them, Gundelia
rosea locally known as kengerreş were grown in West Iran, Northern of
Iraq and Eastern parts of Turkey. It has been traditionally used in the treatment of diabetes and epilepsy in Turkey. Additionally, a chewing gum has been obtained and sold by local healers from its latex, which is used in the treatment of digestive problems. Moreover, in rural
areas of Eastern Anatolia such as Gürpınar provinces, a local coffee is
prepared from seeds of Gundelia rosea. Infusion and/or decoction pre-pared from Gundelia rosea has been extensively used traditionally for the treatment of epilepsy, diabetes and digestive ailments in Eastern Anatolia. This study focused on the answer of the following question: What are the biologically important chemical compounds of the Gundelia rosea? and is there any association between biological activi-ties and traditional usage of Gundelia rosea? Therefore, this study
⁎ Corresponding author at: Van Yuzuncu Yil University, Faculty of Pharmacy, Department of Pharmaceutical Botany, Campus of Zeve, Van 65090, Turkey.
E-mail address:dalar.abdullah@yyu.edu.tr(A. Dalar).
https://doi.org/10.1016/j.sajb.2019.08.024
0254-6299/© 2019 SAAB. Published by Elsevier B.V. All rights reserved.
Contents lists available atScienceDirect
South African Journal of Botany
aimed to (i) compare traditional preparing methods (infusion and
decoction) and commonly used scientific extraction method
(ethanol-based) in terms of extraction efficiency, (ii) analyze the presence of
biologically active compounds of the extracts, (iii) evaluate total pheno-lics and antioxidant capacities comprehensively through FRAP, ORAC, DPPH, ABTS, CUPRAC, Phosphomolybedenum and metal chelation methods, and (iv) measure the enzyme inhibitory abilities against iso-lated enzymes including AChE, BChE, tyrosinase, amylase, glucosidase, and lipase.
2. Materials and methods 2.1. Plant materials
Seed samples of Gundelia rosea Al-Taey & Hossain were harvested from Konalga village, Çatak/Van city, in the Eastern Anatolia Region of
Turkey, on August 8, 2018 (GPS coordinates 37o5′ 255″N 043o09′
857″E). The identity of plant materials were confirmed at Van
Pharma-ceutical Herbarium, Pharmacy Faculty, Van Yuzuncu Yil University, Van/ Turkey by Abdullah Dalar, PhD and Muzaffer Mukemre, PhD and the voucher sample was kept properly (Herbarium code: VPH-379; Collec-tor code:AD-802). The study materials were dried suitably in the dark
and subsequently subjected to grinding process, and stored at−20 °C
until extraction procedure. 2.2. Chemicals
All chemicals were obtained from Sigma–Aldrich, Inc. (St Louis, MO,
USA) and were of analytical or HPLC grade. 2.3. Preparation of extracts
2.3.1. Ethanol-based lyophilized extract
Ethanol-based lyophilized extract was prepared as described
previ-ously (Dalar and Konczak, 2013).
2.3.2. Lyophilized infusion extract
Lyophilized infusion extract was prepared according toBaytop
(1999). Briefly, the ground air-dried seed samples were mixed with a
10-fold volume of boiled mineral water (gr/ml), incubated for 10 min.
Subsequently, the mixture wasfiltered through cotton and vacuum
fil-tration (45μm) with the supernatant collected. The supernatant of
infu-sion was evaporated under reduced pressure at 37 °C using a rotary evaporator (Rotavapor R-205; Buchi, Switzerland). The derived
concen-trated infusion fraction was freeze-dried under a vacuum at−51 °C to
obtainfine lyophilized infusion powder.
2.3.3. Lyophilized decoction extract
Lyophilized decoction extract was prepared according toBaytop
(1999). Briefly, the ground air-dried seed samples were mixed with a
10-fold volume of cold mineral water (gr/ml), and heated until boiling. The mixture kept in boiled water for 3 min and then the mixture was
re-moved from heat, and stood for 10 min to befiltered. Subsequently, the
mixture wasfiltered through cotton and vacuum filtration (45 μm) with
the supernatant collected. The supernatant of decoction was evaporated individually under reduced pressure at 37 °C using a rotary evaporator (Rotavapor R-205; Buchi, Switzerland). The derived concentrated
de-coction fraction was freeze-dried under a vacuum at−51 °C to obtain
fine lyophilized decoction powder. 2.4. Antioxidant capacity
Folin–Ciocalteu reducing (Total phenolic content), total reducing
(FRAP), and oxygen radical scavenging (ORAC) capacities of the extracts
were measured as described previously byDalar and Konczak (2013).
The total antioxidant (phosphomolybdenum method), DPPH radical
scavenging, ABTS radical cation scavenging, the cupric ion reducing (CUPRAC), and metal chelating activities of the extracts were
deter-mined as described previously described byUysal et al. (2017).
2.5. Enzyme inhibitory activities
Cholinesterase (ChE),α-amylase, α-glucosidase, and tyrosinase
in-hibitory activities of the extracts were determined according toZengin
(2016). The pancreatic lipase activity was assayed as described
previ-ously (Dalar and Konczak, 2013).
2.6. HPLC-MS/MS analysis
Phenolic compounds of the extracts were identified and quantified
using high liquid chromatography–diode array–mass spectrometry
(LC-DAD-MS/MS) as reported previously (Dalar and Konczak, 2013).
2.7. GC–MS analysis
Fatty acids present in extracts were analyzed by gas
chromatogra-phy–mass spectrometry (GC/MS) using a headspace solid phase micro
extraction as described previously (Uzun et al., 2017).
2.8. Data analysis
The mean values were calculated based on at least three determina-tions (n = 3). One-way ANOVA followed by the Bonferroni post-hoc test was performed to assess differences between the samples at the level of
pb .05 through Graphpad Prism 5 (Graphpad Software, CA, USA).
3. Results and discussion
3.1. Phytochemical profiling
Phytochemical profiling of Gundelia rosea extracts were analyzed via
HPLC-MS/MS (Table 1andFig. 1) and GC–MS (Table 2andFig. 2). Based
on molecular weight, neutral loss, fragment ions, spectrum properties and co-chromatography analyses, two major phenolic compounds were detected in the extracts. The dominated compound showed a
neg-atively charged molecular ion ([M− 1]−) at m/z 353 and produced MS/
MS fragment ions of 191, 179 and 173 m/z respectively. According to MS/MS data (neutral loss, molecular weight, fragmentation pattern
and absorbance spectrum) and differential ion mobilities (Willems
et al., 2016), this compound was tentatively identified as
4-O-Caffeoylquinic acid. Compound 2 was tentatively characterized as luteolin hexoside since it had negatively charged molecular ion
([M– 1]−) at m/z 447 and a MS/MS fragment of 287/285 m/z, and a
loss of 162 amu. (Table 1andFig. 1). Additionally, traces of caffeic acid
and luteolin compounds were also detected in the extracts (Table 1).
GC–MS analysis showed that lipophilic composition of the extracts
was mainly composed of fatty acids. Based on the MS data, seven fatty
Table 1
HPLC-MS/MS profiles of Gundelia rosea seed extracts. Individual phenolic compounds MS/MS Concentration (mg/g extract) [M + 1]+ /
[M−1]− (m/z)(+/−) Ethanol Infusion Decoction
4-Caffeoylquinic acid −/353 −/171, 173, 191 50.1 ± 1.4a 21.5 ± 0.8b 17.8 ± 0.8c Caffeic acid −/179 −/135 T T T Luteolin −/285 −/133 T T T Luteolin hexoside 449/447 287/285 8.8 ± 0.6a 3.9 ± 0.2b 3.0 ± 0.1c Means with different letters in the same raw were significantly different at the level (pb .05); n = 3. T: trace level.
acids were identified in the extracts (Table 2,Fig. 2) with the dominancy of linoleic acid, followed by oleic, palmitic and stearic acids. Addition-ally, traces of arachidic, linolenic and oxiraneoctanoic acids were also
detected in the extracts (Table 2).
Chlorogenic acids, which are the ester of quinic and caffeic acids are among common phenolic acids present in medicinal plants and there-fore their biological activities including antioxidant, antidiabetic,
anti-convulsant activities were investigated (Kartini et al., 2014; Oboh
et al., 2015; Alam et al., 2016; Willems et al., 2016). The dominated
phenolic compound of the extracts was 4-O-Caffeoylquinic acid that contributed 83%, 82.6% and 84.7% of the phenolic composition of etha-nol, infusion and decoction extracts respectively. Our chromatographic findings are in concordance with the scientific literature of Gundelia
species. For instance,Asgari et al. (2015)reported the presence of caffeic
and chlorogenic acids as major phenolics and linolenic acid as major
fatty acids of Gundelia tournefortii. In a study conducted bySekeroglu
et al. (2012)palmitic, stearic, oleic and linoleic acids were found as
dominant fatty acids of Gundelia tournefortii. The presence of chlorogenic acid and its isomers including cryptochlorogenic acid (4-O-Caffeoylquinic acid) in Gundelia species was reported previously by
Haghi et al. (2011). Thesefindings suggest that, chlorogenic acid and
its isomers are among the significant marker phenolic compounds of
Gundelia species.
Application of an organic solvent such as ethanol or boiling water might extract some toxic compounds, and therefore the application of cold water is proposed in order to minimize the extraction of possible
toxic compounds present in plant matrix (Farzaneh and Carvalho,
2015). Based on our chromatographic studies, not any toxic compounds
were detected in ethanol extract, heat treatment used infusion, and de-coction extracts which suggest that the level of toxic substance might be at trace or negligible levels and can explain the extensive utilization of Gundelia rosea in folk medicine.
3.2. Antioxidant capacities
Antioxidants which are mainly act to deactivate the free radicals can be categorized according to their activity (enzymatic or
non-enzymatic), solubility (hydrophilic or lipophilic), and size (Nimse and
Pal, 2015). Therefore, various methods based on different reaction
mechanisms should be utilized in order to reveal the comprehensive an-tioxidant capabilities of the extract tested. The anan-tioxidant activities of Gundelia rosea extracts were evaluated comprehensively through
com-plementary methods (Table 3). Ethanol extract contained a high level of
total phenolics (55.3 mg Gallic acid Eq./g extract) and had pronounced
levels of reducing (1683μmol Fe2+and 214.1 mg Trolox Eq./g extract
for FRAP and CUPRAC respectively) and radical scavenging (ORAC:
2241.9μmol, DPPH: 91.7 mg, ABTS: 141.2 mg Trolox Eq./g extract)
and total antioxidant (Phosphomolybdenum: 1.39 mmol Trolox Eq./g extract) activities. These results showed that ethanol-based extract had superior levels of antioxidant activities than those of the water-based infusion and decoction extracts, which suggest the superior ex-traction potential of ethanol solvent in terms of major bioactive
com-pounds of Gundelia rosea. This hypothesis was partly confirmed via
the highest total phenolic content of the ethanol extraction. In addition,
Table 2
GC–MS profiles of Gundelia rosea seed extracts. No Retention
time
Compound Fragment ions
Relative concentration (%) Ethanol Infusion Decoction 1 36.77 Palmitic acid 60, 73, 83, 97, 129, 143, 157, 171, 185, 199, 213, 227, 239, 256 18.60 11.02 10.98 2 40.40 Stearic acid 55, 60, 73, 87, 115, 129, 143, 157, 171, 185, 199, 213, 227, 241, 255, 267, 284 3.68 3.40 3.56 3 41.17 Oleic acid 55, 69, 83, 97, 111, 125, 151, 165, 180, 195, 207, 222, 246, 264 20.31 30.95 30.91 4 42.47 Linoleic acid 55, 67, 81, 95, 110, 123, 136, 150, 164, 185, 209, 223, 241, 262, 280 53.33 52.16 52.12 5 43.14 Arachidic acid 41, 55, 57, 69, 73, 85, 97, 129, 157, 171, 185, 213, 250, 269, 312 T ND ND 6 43.77 α-Linolenic acid 55, 67, 79, 93, 108, 121, 135, 149, 177, 191, 209, 222, 235, 249, 264, 278 T ND ND 7 49.75 Oxiraneoctanoic acid 41, 55, 57, 69, 83, 97, 109, 113, 120, 124, 139, 155, 167, 185 T T T 500 400 300 200 100 0 0.0 5.0
Retention time (minutes)
4-0-caf
feoylquinic acid
Luteolin hexoside
HPLC profile of Gundelia rosea (326 nm)
10.0 15.0 20.0 25.0 30.0
the results showed that the major compounds of the extracts were less sensible to the heat treatment, which was resulted in lesser total
pheno-lics and antioxidant capacities in decoction extracts (Table 3). The total
phenolic content and antioxidant activities of Gundelia rosea were
supe-rior to ethanol extract obtained from Gundelia tournefortii (Sekeroglu
et al., 2012).Fraisse et al. (2011)reported that caffeoyl derivatives
were the major antioxidant compounds of wild herbs of several species belong to Asteraceae family which propounded that chlorogenic acids are among the major key antioxidant compounds of Asteraceae family
specifically Gundelia species.
3.3. Inhibitory effects on tested enzymes
The increase of global health problems across the world conduced
the enzymes to be one of the most significant pharmacological patterns
(Copeland et al., 2007). For instance,WHO (2018)reported that
approx-imately 1.9 billion people which 18% of them were children have been
affected by obesity (WHO, 2018). Moreover, a dramatical prevalence
(from 4.7% to 8.5%) of diabetes mellitus has been arised between the
pe-riods of 1980 and 2014 (Pesce et al., 2019). Therefore, modest strategies
are needed for the management of such diseases. Such an approach-ment can alleviate the symptoms of public health diseases. Among them, key enzyme inhibitory strategy effectively applied as pharmaceu-tically. For instance, cholinesterase is a target for preventing Alzheimer's
disease, which hydrolyzes acetylcholine in the synaptic of gap (Jiang
and Gao, 2019). Similarly, pancreatic lipase is the main enzyme of
hy-drolysis of triglycerides in gastrointestinal tract, thus inhibiting its
activ-ity may be linked to reduced lipid absorption and obesactiv-ity (Hamdan
et al., 2019). In this context, several drugs (tacrine for cholinesterases;
kojic acid for tyrosinase; volgibose for amylase and orlistat for lipase) have been produced as inhibitor agents in pharmaceutical industry. However, the side effects including diarrhea, abdominal disturbance
or toxicity (Buchholz and Melzig, 2015; Thakur et al., 2019; Palacios
et al., 2019) of such inhibitors limited their utilization properly. Thus,
novel alternative inhibitors from natural sources with minimum side ef-fects are needed.
The enzyme inhibitory effects of G. rosea extracts were investigated on several enzymes including cholinesterases, tyrosinase, amylase,
glu-cosidase and lipase (Table 4). Solely the ethanol extract was active on
cholinesterases (4.30 mg GALAE/g for AChE and 3.40 mg GALAE/g for BChE), while infusion and decoction were not active on these enzymes.
The best tyrosinase inhibitory activity was observed in ethanol extract with the value of 120.25 mg KAE/g, followed by infusion and decoction. Antidiabetic potential of the extracts were assayed through amylase and glucosidase enzymes and similar to cholinesterases and tyrosinase, the superior inhibitory abilities were detected in ethanol extract. Moreover, infusion and decoction did not exhibit inhibitor effect on glucosidase. With regard to lipase inhibition, the ethanol extract was the best inhib-itor among all extracts. Generally, the antioxidant and enzyme inhibi-tory effects for G. rosea extracts followed the same pattern of ethanol
N infusion N decoction. This finding is in agreement withYao et al.
(2009),Reza et al. (2018),Moein et al. (2017), andSun et al. (2017),
who reported the positive correlations between total phenolics and en-zyme inhibitory effects. Also, the highest level of 4-caffeoylquinic acid and luteolin hexoside was found in ethanol extract and these
Table 3
Total phenolic contents and antioxidant activities of Gundelia rosea seed extracts. Ethanol Infusion Decoction Antioxidant activity Total phenolics content-FCR1 55.3 ± 3.2a 32.9 ± 2.0b 23.1 ± 0.5c FRAP2 1683.3 ± 71.4a 810.3 ± 55.8b 532.8 ± 6.3c ORAC3 2241.9 ± 42.7a 742.9 ± 20.6b 701.0 ± 30.5c DPPH4 91.7 ± 3.5a 28.4 ± 3.7b 21.0 ± 2.7c ABTS5 141.2 ± 2.1a 83.2 ± 6.1b 58.1 ± 2.0c CUPRAC6 214.1 ± 3.7a 132.4 ± 3.8b 106.6 ± 8.4c Phosphomolybdenum7 1.39 ± 0.07a 0.80 ± 0.02b 0.63 ± 0.02c Metal Chelation8 28.7 ± 1.2b 47.5 ± 0.9a 46.6 ± 0.8a Means with different letters in the same raw were significantly different at the level (p b .05); n = 3.
1 Folin–Ciocalteu values – mg Gallic acid Equivalent/g extract, 2
Ferric reducing antioxidant power– μ mol Fe2+
/g extract,
3 Oxygen radical absorbance capacity -μ mol Trolox Equivalent/g extract, 4 DPPH radical scavenging activity - mg Trolox Equivalent/g extract, 5
ABTS radical scavenging activity - mg Trolox Equivalent/g extract,
6
Cupric ion reducing antioxidant capacity - mg Trolox Equivalent/g extract,
7
Phosphomolybdenum total antioxidant capacity - mmol Trolox Equivalent/g extract,
8
Metal chelation activity - mg EDTA Equivalent/g extract.
Retention time (minutes)
Palmitic acid
Oleic acid
Stearic acid
Linoleic acid
GC-MS profile of Gundelia rosea
15.00 0 1000000 2000000 3000000 4000000 5000000 6000000 7000000 8000000 9000000 1e+07 25.00 30.00 35.00 40.00 45.00 50.00 55.00 20.00
components have been already reported as antioxidant, antidiabetic,
anti-Alzheimer or antiobesity agents (Akihisa et al., 2013; Iwai et al.,
2004; Hu et al., 2015; Szwajgier et al., 2017; Zang et al., 2016; Choi
et al., 2014; Kawser Hossain et al., 2016). From this point forth, these
components could be among the main contributors of the biopharma-ceutical properties of Gundelia rosea extracts.
4. Conclusions
• This work is the first report of chemical composition, antioxidant and enzyme inhibitory properties of G. rosea extracts.
• Ethanol extract exhibited the highest biological activities.
• 4-Caffeoylquinic acid, luteolin hexoside, and fatty acids were detected as major phytochemical compounds of Gundelia rosea.
• Our findings indicate that chlorogenic acids might be among the key phenolic compounds of Gundelia species.
• Ethanol solvent was more efficient than that of the water solvent in terms of extraction capability of bioactive compounds.
• Our findings suggest a pronounced biopharmaceutical potential of Gundelia rosea for pharmaceutical industry.
Funding source
This research didn't receive any grant from public, commercial, or private sectors.
Declaration of Competing Interest
The authors declare that there is no conflict of interest.
Acknowledgements None.
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Table 4
Enzyme inhibitory activities of Gundelia rosea seed extracts.
Ethanol Infusion Decoction Enzyme ihibitory activity AChE1 (mg Galanthamine Eq./g extract) 4.30 ± 0.09 NA NA BChE2 (mg Galanthamine Eq./g extract) 3.40 ± 0.21 NA NA Tyrosinase (mg Kojic acid
Eq./g extract) 120.25 ± 0.5a 19.75 ± 1.1b 14.83 ± 2.3c Amylase3 (mmol Acarbose Eq./g extract) 0.61 ± 0.01a 0.11 ± 0.01c 0.13 ± 0.01b Glucosidase4 (mmol Acarbose Eq./g extract)
11.91 ± 0.01
NA NA Lipase5(μmol Orlistate Eq./g
extract) 53.4 ± 2.4a 9.6 ± 0.7b 6.4 ± 0.5c Means with different letters in the same raw were significantly different at the level (p b .05); n = 3. NA: not active.
1 Acetylcholinesterase. 2 Butyrylcholinesterase. 3 Alpha-amylase. 4 Alpha-glucosidase. 5 Pancreatic lipase.
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