Journal of Photochemistry & Photobiology, B: Biology 195 (2019) 51–57

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Journal of Photochemistry & Photobiology, B: Biology

journal homepage: www.elsevier.com/locate/jphotobiol

Fabrication of resveratrol coated gold nanoparticles and investigation of T

their effect on diabetic retinopathy in streptozotocin induced diabetic rats
Yi Donga, Guangming Wana, , Panshi Yana, Cheng Qiana, Fuzhen Lia, Guanghua Pengb
⁎

a
Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Henan Province, Eye Hospital, Zhengzhou 450052, China
b
School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 45000, China

ABSTRACT

This study includes the fabrication of gold nanoparticles (AuNPs) with the help of a plant polyphenol called Resveratrol through an ecofriendly synthetic process
without any use of harmful reductants. In the fabrication of AuNPs, Resveratrol acts as both stabilizing and reducing agent. The prepared AuNPs is tested on
streptozotocin (STZ) induced diabetic rats for their amelioration consequence. The images of TEM displayed the development of spherical nanoparticles (NPs) with a
median of 20 nm particle size. The STZ injected diabetic rats were administrated orally with calcium dobesilate (CD; 500 mg/kg/day) or AuNPs (200, 300 mg/kg/
day) for a period of 3 months. The characteristics displayed by AuNPs were found to be similar with CD in decreasing permeability of blood–retinal barrier in STZ
injected diabetic rats. The retinal vessels in the AuNPs administrated diabetic rats were observed to be decreased through the retinal histopathological examination.
In the AuNPs administrated diabetic rats, the retinal expression of renal Pigment Epithelium-Derived Factor (PEDF) was observed to be increased and the Vascular
Endothelial Growth Factor (VEGF-1), which was increased in diabetic rats was declined on treating with AuNPs. On treating the STZ injected diabetic rats with
AuNPs, all the retinal mRNA expressions of VEGF-1, Tumor Necrosis Factor (TNFα), Monocyte Chemotactic Proteins-1 (MCP-1), Intercellular Adhesion Molecule-1
(ICAM-1), and Interleukin (IL)-6, IL-1β were observed to be reduced. Furthermore, AuNPs can reduce phosphorylation of Nuclear Factor Kappa B (NF-κB) p65 and
Extracellular signal Regulated Kinase (ERK) 1/2 along with a growth in nuclear translocation of pNF-κB p65 produced by STZ. To conclude, the protective effect of
AuNPs on STZ injected diabetic rats could help in redeveloping the balance among the inhibitors and stimulators of angiogenesis. Furthermore, on treating with
AuNPs results in inhibiting the signaling pathway of ERK1/2 as well as with amelioration of retinal inflammation through trans repression of NF-κB.

1. Introduction oxidative stress worsening, proinflammatory cytokines, leading to

Diabetic retinopathy (DR) is one among the most regular difficulty
found in diabetes and is an important reason for acquired loss of sight
among the public of working age group [1,2]. The early stage in-
dicators of DR is persistent apoptosis of vascular and neural cells in the
eye tissue [3,4]. DR leads to the retinal edema, detachment, neo-
vascularization and blood retinal barrier breakdown which leads to loss
of vision. Even though the exact mechanism of DR is not known, the
reasons may include oxidative stress caused by hyperglycemia, im-
balance among generations of Reactive Oxygen Species (ROS) and the
neutralization of ROS by antioxidants leads to pathogenesis of DR
[3,5].
Hyperglycemia caused by diabetes results in oxidative stress
through improvement in glucose oxidation, fluctuations in polyol and
protein kinase C, hexosamine pathways and improved glycation end
products [6]. Reduction of antioxidants, glycation or Peroxidation of
lipids, DNA and proteins, defenses and inflammation of tissues are
persuaded by oxidative stress [7,8]. Most of the hyperglycemia men-
tioned above persuaded pathways meet to activate transcription factor
(NF-kB factor), which further subsidizes to additional development in
apoptosis and programmed cell death [9,10]. On the other hand, the
eye cells are more liable to oxidative stress when compared to other
body tissues due to rich polyunsaturated fatty acids in membranes and
have major glucose oxidation and oxygen consumption [11,12].
On the other hand, bio fabrication of metal NPs with the help of
plant extracts, and biomolecules became the scientific attraction due to
their prominent applications in biology and medicine [13]. For ex-
ample, Rajakumar and Abdul Rahuman showed the larvicidal activity
of noble metal NPs against vectors of filariasis and malaria and the NPs
were prepared using Eclipta prostrata leaf extracts [14]. In the same
way, important antibacterial activity against clinically isolated patho-
gens was reported for AgNPs and AuNPs [15].
Resveratrol (trans-3,5,4′-trihydroxystilbene), a polyphenol present
in different parts of several plants. It has very good properties such as
anticoagulant, anticancer, anti-inflammatory, cardio protective, life-
span extending, vasoprotective effects and antioxidant properties
[16–18]. Hence, many studies were executed on the important role of
this polyphenol in treatment or prevention of complications related to
diabetes [16,19]. Based on the above reports, we planned to prepare
Resveratrol coated gold nanoparticles (AuNPs) via a green synthetic

⁎
Corresponding author at: First Affiliated Hospital of Zhengzhou University， No.1 of East Jianshe Road, Zhengzhou, Henan Province, China.
E-mail address: wanguangming@yahoo.com (G. Wan).

https://doi.org/10.1016/j.jphotobiol.2019.04.012
Received 3 April 2019; Received in revised form 25 April 2019; Accepted 30 April 2019
Available online 02 May 2019
1011-1344/ © 2019 Published by Elsevier B.V.
Y. Dong, et al.
approach for their application in diabetic retinopathy.
In this work, we showed the synthesis of AuNPs using Resveratrol, a
plant polyphenol via a green synthetic approach without using any
toxic reductants. Resveratrol acts as stabilizing and reducing agent
during the synthesis of AuNPs. The obtained AuNPs are checked for
their amelioration effect on STZ-induced DR in rats.
2. Materials and methods
2.1. Materials
Chloroauric acid (HAuCl4), Resveratrol, Streptozotocin and all other
chemicals, solvents were procured from Sigma-Aldrich Chemicals,
Shanghai.
2.2. Synthesis of AuNPs
About 10 mg of Resveratrol was added to 2 mM HAuCl4 (5 mL) and
the obtained solution was allowed for shaking at a temperature of 27 °C
for about half an h. The variation in the reaction solution color from
colorless to ruby red indicated the formation of AuNPs.
2.3. Generation of diabetic rat model
8–10 weeks aged Wistar male rats of 200–250 g weight was ac-
quired from National laboratory animal center, Taiwan. Streptozotocin
of 60 mg/kg was sedated through a single intravenous injection to in-
duce diabetes in the rats. Post 1 week of sedating, non-fasting animals
with N350 mg/dL of blood glucose levels, glucosuria, and polyuria were
considered as diabetic rats and utilized for the investigation. Following
the guidelines for use and care of Animal Welfare Act, all the animal
treatments were performed. IACUC has accepted all the conducted
studies with ethical clearance.
2.4. Treatment protocols
At about fourteen days after injecting STZ, animals were treated by
oral gavage for consecutive 3 months once/day with 200 or 300 mg/kg
quantity of AuNPs in a volume of 1.5 mL/kg purified water. One of the
previous reports, which demonstrated the potential efforts of Zingiber
zerumbet (L.) Smith rhizome (AuNPs) at 200 or 300 mg/kg in enhancing
the insulin resistance of diabetic rats, was followed in selecting the
dosage regime [20]. Another set of STZ injected diabetic rats admini-
strated orally for 3 months with a therapeutic agent, Calcium Dobesilate
used for preventing the diabetic retinopathy, 500 mg/kg/day of dosage
[21], which was selected as a positive control in this study. A group of
vehicle served ordinary and STZ injected diabetic rats were served with
distilled water of 1.5 mL/kg only, at the similar period of treatment.
During the entire investigation period, the body weight and the levels of
glycosylated hemoglobin (HbA1c), plasma glucose were continuously
examined. The plasma levels of glucose were determined with the help
of a diagnostic kit purchased from Sigma-Aldrich, Shanghai. The HbA1c
levels were measured with the help of Commercial Enzyme-linked Im-
munosorbent Assay (ELISA) kits purchased from Integrated Bio Ltd.,
Taiwan. All the examinations were conducted as per the guidelines
instructed by the manufacturers.
All the rats were fasted for about 18 h (overnight) at the end of the
experiments, and then sedated with sodium pentobarbital (60 mg/kg)
with the help of an intraperitoneal (i.p.) injection. The retina of the rats
were separated and blood was extracted straight from the abdominal
aorta of every rat. Cold normal saline was used to wash the separated
retina, and then utilized for the histopathological investigations and in
the development of eye homogenate.
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Journal of Photochemistry & Photobiology, B: Biology 195 (2019) 51–57
2.5. Measurement of retinal vascular permeability
One of the pervious described methods, Evans Blue (EB) dye in-
jection technique was followed to measure the retinal endothelial
permeability, with slight modifications [22]. In brief, EB that was
purchased from Sigma-Aldrich, Shanghai, was suspended in saline of
30 mg/mL followed by filtering, and then injected at a dose of 45 mg/kg
via tail vein within 10 s. Pentobarbital (40 mg/kg body wt) was utilized
to anesthetize the rats post 2 h of injecting dye. Cardiac perfusion (CP)
was conducted through the left ventricle on opening the chest cavity,
and paraformaldehyde of 1% in 0.05 mol/L citrate buffer (pH 3.5)
under a 120 mmHg of constant pressure was applied to perform the CP.
Retinas were cautiously examined under an operating microscope im-
mediately after performing CP. Weights of the retinas were measured
after fully drying at a temperature of 4 °C. Each sample was incubated
in formamide of 150 μL at a temperature of 70 °C for about 18 h to
extract EB dye. Supernatant of 100 μL at 620 and 740 nm was used to
measure the absorbance. Standard curve was used to calculate the EB's
(ng/mg protein) concentration in the extracts and normalized with the
help of the dry retina weight (mg).
2.6. Histological assessment
The solution of 4% paraformaldehyde was used to suspend the rat
retinas after isolating. The tissues of the retina were sectioned (5 μm)
subsequently, stained with eosin and hematoxylin (E&H), and then
passed under the operational microscope for the examination. A digital
camera system (C3040-AD6, Shanghai, china) with high resolution was
used to capture the digital images and the digital camera was linked to
the operational microscope as well as the desktop computer. The retinal
images of the eyes were captured at 1500 mm of similar distance from
the optic nerve.
2.7. Statistical analysis
All the statistical information provided were represented as the
mean ± standard deviation (SD). Data was conducted with ANOVA.
To determine the source of significant variations we utilized Dunnett
range post-hoc comparisons, wherever applicable. The value of P less
than 0.05 was statistically considered as significant.
3. Results
3.1. Characterization
The reduction of AuNPs was initially investigated by recoding the
UV–visible spectrum of AuNPs with reaction time. The optical absor-
bance spectrum of the green synthesized AuNPs is shown in Fig. 1A.
The presence of a surface plasmon resonance absorption band at
530 nm, found in spectrum of synthesized AuNPs, further suggested the
AuNPs formation. Fig. 1B. showed the XRD pattern of fabricated
AuNPs. The XRD results shown in Fig. 1B. revealed the crystalline
nature of AuNPs, which further confirmed face cantered cubic (FCC)
structure of fabricated AuNPs, with characteristic peaks found at 77.7o,
64.7o, 44.48o and 38.2o, with corresponding indexing planes found at
(311), (220), (200) and (111) correspondingly. The crystalline nature of
the synthesized AuNPs was confirmed with corresponding JCPDS File
No.87–0720.
Fig. 2A, B represented the TEM microscopic images of synthesized
AuNPs. It is found that AuNPs are polydisperse and spherical in nature
with an average of 10 mm particle size. Also, the SAED results of
AuNPs, represented in Fig. 2C, revealed the crystalline nature of the
prepared AuNPs with selected area diffraction spots which are well-
distinguished.
Fig. 3 represented the FTI-R results of the bio fabricated AuNPs. It is
found the existence of vibrational bands found at 1383 and 3395 cm−1
Y. Dong, et al. Journal of Photochemistry & Photobiology, B: Biology 195 (2019) 51–57

Fig. 1. UV–visible absorption spectrum (A) and XRD pattern (B) of AuNPs.

Fig. 2. TEM images (A, B) and SAED pattern (C) of AuNPs.

Fig. 4. Retinal vascular permeability in STZ injected diabetic rats exposed

3 months with AuNPs 200, 300 mg/kg/day or CD 500 mg/kg through oral ga-
Fig. 3. FTIR spectrum of AuNPs.
vage.

corresponding to tertiary alcoholic and hydroxyl stretching vibrations.

The vibrational bands located at wavenumber of 1055, 1615 and 1712,
are due to –C-O-C, –COOH and ketonic, functionalities, correspond-
ingly.
3.2. Fasting blood glucose, body weight and glycosylated hemoglobin
content
When related with ordinary rats, STZ induced diabetic rats were
identified to have obvious loss in weight, during the 3 months
experiment period. Also during the experiment period, no significant
decrease in the body weight was observed in the STZ induced diabetic
rats treated with CD or AuNPs alone. When compared with the ordinary
control rats, STZ injected diabetic rats were noticed to have obvious
growth in the fasting blood glucose and this modification in the blood
glucose was noticed to be more at the end of third month after inducing
the diabetes. The levels of glucose in STZ injected diabetic rats were
noticed to be decreased after treating with AuNPs, and it sustained the
levels at 290 to 350 mg/mL approximately. The obvious decrease in the

Table 1
Variation in the content of glycosylated hemoglobin, fasting blood glucose and body weight in the investigational rats at the end of 3 months treatment.
Normal vehicle STZ-Diabetic vehicle AuNPs-200 AuNPs-300 CD

Plasma glucose (mg/dL) 91.3 ± 5.7 418.3 ± 12.1 348.5 ± 14.2 290.4 ± 13.2 396.9 ± 14.7
Body weight (BW) (g/rat) 321.4 ± 12.6 216.3 ± 14.7 262.3 ± 11.2 281.8 ± 13.4 257.7 ± 15.3
HbAlc (%) 4.8 ± 1.1 16.2 ± 1.2 13.8 ± 1.3 11.7 ± 1.1 15.5 ± 1.0

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Fig. 5. Retinal H&E stained images from rats undergone for 3 months treatment, Normal rats exposed with vehicle (normal + vehicle), STZ-diabetic rats exposed
with vehicle (STZ + vehicle), and STZ-diabetic rats exposed with AuNPs at 300 mg/kg/day (STZ + AuNPs), where vehicle is distilled water.

Fig. 6. Representing the thickness of the retina (A) and ganglion cell layers and nerve fiber (B) determined in every rats group with various treatments.

Fig. 7. Representation of the levels of mRNA (A) and protein (B) of VEGF and PEDF in the eyes of rats or STZ injected diabetic rats undergone for 3 months treatment,
Normal rats exposed with vehicle (normal + vehicle), STZ-diabetic rats exposed with vehicle (STZ + vehicle), and STZ-diabetic rats exposed with AuNPs
(STZ + AuNPs), where vehicle is distilled water.

54
Y. Dong, et al.
Fig. 8. The ratio of VEGF-to-PEDF in the eye of rats or STZ injected diabetic rats
undergone for 3 months treatment, Normal rats exposed with vehicle (normal
+ vehicle), STZ-diabetic rats exposed with vehicle (STZ + vehicle), and STZ-
diabetic rats exposed with AuNPs (STZ + AuNPs), where vehicle is distilled
water.
levels of blood glucose when STZ induced diabetic rats were admini-
strated with AuNPs 300 mg/kg/day (30.7 ± 6.2%) for about 3 months
were indicated in Table 1. When related with ordinary rats, the HbA1c
value was noticed to be greater in the STZ induced diabetic rats (as
shown in Table 1). The levels of HbA1c in STZ induced diabetic rats
treated with AuNPs 300 mg/kg/day for 3 months were noticed to be
reduced by 26.5 ± 1.7% when compared with the value in STZ in-
duced diabetic rats that served with vehicle. The treatment of CD did
not reduce the hyperglycemia nor inhibit the HgbA1c in STZ induced
diabetic rats (Table 1).
3.3. Retinal vascular permeability
When compared with the permeability values of retinal blood vessel
in normal control group (2.8 ± 1.5 ng/mg), we observed an obvious
increase in the values of STZ induced diabetic rats (13.2 ± 1.6 ng/mg)
(as shown in Fig. 4). We observed an obvious decrease in the retinal
vascular permeability when the STZ induced diabetic rats were treated
with CD (7.8 ± 1.4 ng/mg; Fig. 1) for 3 months, on treating with
AuNPs 300 mg/kg/day (6.2 ± 1.2 ng/mg, Fig. 4) the values were even
reduced to a further extent.
3.4. Morphological variations in the retina
Fig. 5A represents the morphological modifications in rat's retinas.
We observed the presence of more number of vessels in the Outer Nu-
clear Layer (OPL), Inner Nuclear Layer (INL) and Ganglion Cell Layer
(GCL) in the STZ induced diabetic rats when related with those of
normal control group rats (Fig. 25A), and these vessels were observed
to be decreased on treating with AuNPs (300 mg/kg) (Fig. 5A).
Fig. 9. Representation of Protein (A) and mRNA levels of IL-6, TNFα and IL-1β (B) in rat retinas undergone for 3 months exposure.
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Journal of Photochemistry & Photobiology, B: Biology 195 (2019) 51–57
Fig. 6 represents the measured retinal thickness and Nerve Fiber
Layer (NFL), GCL. When compared with the retina of ordinary control
animals, the STZ injected diabetic rats retinas were noticed to be sig-
nificantly thinner. The retinas of the STZ induced diabetic rats were
observed to be thicker than the vehicle served group, after the ad-
ministration with 300 mg/kg/day AuNPs (Fig. 6). Additionally, GCL
and NFL were noticed to be thicker in the STZ induced diabetic rats
treated with AuNPs (300 mg/kg/day), when related with the levels of
the vehicle served rats (Fig. 6).
3.5. The gene expression of retinal pro-angiogenic factors
In the STZ injected diabetic rats, the retinal expression of vascular
endothelial growth factor (VEGF) was observed to be increased sig-
nificantly at both the protein and mRNA levels when compared with the
levels in ordinary rats. When the STZ induced diabetic rats were treated
with AuNPS (300 mg/kg/day), it was noticed that the protein and
mRNA levels had a decrease of 35.7 and 30.8%, respectively, when
matched with the observed levels of vehicle treated (Fig. 7A & B).
In the protein and mRNA levels of pigment epithelium-derived
factor (PEDF), no significant changes were noticed among STZ injected
diabetic rats when related with the ordinary control rats (Fig. 7A & B).
An obvious increase in both the levels of retinal mRNA and protein of
VEGF was observed in the STZ induced diabetic rats when treated with
AuNPS (300 mg/kg/day) (Fig. 7A & B).
The ratio of VEGF-to-PEDF was noticed to be increased by 3.1-fold
in the STZ injected diabetic rats when related with the ordinary control
rats (Fig. 8), further, on treating with AuNPS (300 mg/kg/day) which
were observed to be declined by 61.4%. (Fig. 8).
3.6. The expression of retinal inflammatory cytokines
In the STZ injected diabetic rats, it was noticed that the retinal
protein level of Tumor Necrosis Factor (TNFα) increased significantly
when compared with normal control group, which were further noticed
to be declined by 20.7% on treating with AuNPs (300 mg/kg/day)
(Fig. 9A). When related with the normal control group, STZ induced a
3.1-fold and 2.8-fold induction in the retinal interleukin (IL) IL-6 and
IL-1β proteins, respectively (Fig. 9A). On treating the STZ induced
diabetic rats with AuNPs (300 mg/kg/day), the protein levels of IL-6
and IL-1β in the eye was observed to be reduced by 33.9% and 37.5,
respectively when related with the vehicle served animals (Fig. 9A).
When compared with the level of retinal TNFα mRNA in the normal
control group, an obvious increase was noticed in the level of STZ in-
jected diabetic rats (Fig. 9B), which was downregulated by
30.8 ± 1.9% on treating with AuNPs (300 mg/kg/day) daily for
3 months (Fig. 9B). In the STZ injected diabetic rats, an obvious in-
crease of 2.7 and 3.3-fold was noticed in the levels of retinal mRNA of
Y. Dong, et al.
Fig. 10. Representation of Protein (A) and mRNA levels of MCP-1, VCAM-1 and ICAM-1 (B) in rat retinas undergone for 3 months exposure.
Fig. 11. Diabetes induced retinal ERK1/2 activation with the effect of different
treatments.
IL-6 and IL-1β, respectively, compared to the levels in ordinary animals
and an obvious reduction was noticed on treating with 300 mg/kg/day
AuNPs daily for 3 months (Fig. 9B).
3.7. The expression of retinal chemokines
When related with the normal control animals, the retinal protein
levels of Vascular Cell Adhesion Molecule 1 (VCAM-1), Intercellular
Adhesion Molecule-1 (ICAM-1) and Monocyte Chemoattractant Protein-
1 (MCP-1) in the STZ injected diabetic rats were greater (Fig. 10A), and
when the STZ injected diabetic rats were served with 300 mg/kg/day
AuNPS, the levels of ICAM-1, VCAM and MCP-1 were noticed to be
declined to 36.8, 36.7 and 34.5%, respectively, when related with the
levels of control group counterparts (Fig. 10A).
In the STZ injected diabetic rats the retinal mRNA levels of MCP-1
Fig. 12. Diabetes induced retinal NF-κB activation with the effect of different treatments.
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Journal of Photochemistry & Photobiology, B: Biology 195 (2019) 51–57
were observed to be higher of about 214.3% of the levels in normal
group (Fig. 10B), and on treating the STZ induced diabetic rats with
300 mg/kg/day AuNPS for continuously about 3 months, the retinal
MCP-1 mRNA levels were noticed to be significantly reduced to 72.9%
when related to the levels in vehicle served group (Fig. 10B). In the STZ
injected diabetic rats, the retinal mRNA levels of VCAM-1 and ICAM-1
were observed to be 3.2 and 3.1 fold greater than the levels of normal
group, respectively. On treating the STZ injected diabetic rats with
AuNPS (300 mg/kg/day) continuously for 3 months resulted in the
decline of retinal mRNA levels of VCAM-1 and ICAM-1 at 25.8 ± 2.4%
and 16.5 ± 2.8, respectively, relative with those in vehicle served
groups (Fig. 10B).
3.8. The changes of ERK1/2 and NF- κB signaling in retina
In the STZ induced diabetic rats retina, the extra cellular signal-
regulated kinase (ERK) 1/2 phosphorylation was identified to be con-
siderably greater relative to the normal control group (Fig. 11). When
the STZ inducted diabetic rats were served with AuNPS 300 mg/kg/day,
the ERK1/2 phosphorylation in retina significantly reduced by 27.4%
relative to that of the vehicle-administrated controls (Fig. 11). The
contents in the total retina ERK remained constant among various
groups (Fig. 11).
The retina protein levels of nuclear factor Kappa B (NF-κB) p65 in
STZ induced diabetic group were observed to be higher of about 2.1-
fold than the levels in the groups treated with vehicles (Fig. 12). On
treating the STZ induced diabetic groups with EZZR 300 mg/kg/day for
continuously 3 months resulted in the decrease of retinal protein levels
of NF-κB to 68.5% to that of the levels in vehicle administrated groups
(Fig. 12).
The retinal activity of NF-κB in STZ induced group was detected to
be 2.4-fold than that of the vehicle treated group (Fig. 12). On treating
the STZ induced group with AuNPS 300 mg/kg/day continuously, for
Y. Dong, et al.
3 months resulted in the decline of NF-κB activity to 48.4% from the
increased activity in STZ induced diabetic rats (Fig. 12).
4. Conclusions
In conclusion, we have showed the fabrication of AuNPs with the
help Resveratrol through an ecofriendly synthetic process without any
use of harmful reductants. The biological experiments revealed that the
AuNPs were found to be similar with CD in decreasing permeability of
blood–retinal barrier in STZ injected diabetic rats. AuNPs administrated
diabetic rats, showed the increased retinal expression of PEDF and
decreased VEGF-1. On treating the STZ injected diabetic rats with
AuNPs, all the retinal mRNA expressions of VEGF-1, TNFα, MCP-1,
ICAM-1, and IL-6, IL-1β were reduced. Furthermore, AuNPs can reduce
phosphorylation of NF-κB p65 and ERK 1/2 along with a growth in
nuclear translocation of pNF-κB p65 produced by STZ. To conclude, the
protective effect of AuNPs on STZ injected diabetic rats could help in
redeveloping the balance among the inhibitors and stimulators of an-
giogenesis. Furthermore, on treating with AuNPs results in inhibiting
the signaling pathway of ERK1/2 as well as with amelioration of retinal
inflammation through Trans repression of NF-κB.
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