Persimmon (Diospyros Kaki) Leaves Extract
(PLE): A Potential Drug for
Ramsha Afzal1, Sualiha Afzal2 and Asad ul-Haq3,4*
1Department of Ophthalmology, The Catholic University of Korea, South Korea
2Pharmacology Unit, Western Sydney University, Australia
3Department of Internal Medicine, Soonchunhyang University Seoul, Korea
4Probiotics Microbiome Convergence Center, Soonchunhyang University, Korea
Submission: February 22, 2022; Published: March 09, 2022
*Corresponding author: Asad ul Haq, Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, 59, Daesagwan-ro, Yongsan-gu, Seoul 04401, Republic of Korea.
How to cite this article:Ramsha A, Sualiha A, Asad u-H. Persimmon (Diospyros Kaki) Leaves Extract (PLE): A Potential Drug for Eye-Related Diseases. Glob J Pharmaceu Sci. 2022; 9(4): 555768. DOI: 10.19080/GJPPS.2022.09.555768.
Persimmon (Diospyros kaki) leaves have been used as a traditional or local medicine for multiple diseases in different eastern countries (Japan, Korea, India, and China) for centuries. In the recent past, several studies have used persimmon leaves extract (PLE) against different eye-related diseases. In this review, we discussed the ethnopharmacological use, therapeutic potentials and future opportunities for research using PLE for different ocular disorders based on the latest research. The pieces of information regarding PLE were collected using Pubmed, ACS, Elsevier, EMBASE, Web of Science, CNKI and different books. It can be concluded from this review that PLE probably have therapeutic potential against inflammation and oxidative stress induced disorders like dry eye disease (DED), corneal neurovascularization (CoNV), glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and edema. However, further investigations are required to discover exact biological compounds involved in the pharmacological effects against the aforementioned diseases. Furthermore, clinical trials are needed to be performed before integrating PLE for medicinal use
Persimmon tree (Family: Ebenaceae, Genus: Diospyros, Specie: kaki or (D.Kaki)) has been cultivated throughout Asian countries (Korea, China, Japan and India) and used as sources of fruit and traditional medicine for centuries [1,2]. Because of its delicious taste and high nutritional values, Persimmon fruit is commonly used in a diet (as a fruit or in teas). Persimmon leaves extract (PLE) have been used as a traditional and/or herbal medicine against internal haemorrhage, ischemia, stroke, angina, paralysis, burns, constipation, and frostbite. PLE has largely been used in cosmetics as they contain anti-ageing compounds, and the compounds present in bark prevent melanin biosynthesis . (D.Kaki) have more nutritional benefits as compared to apples . PLE has anti-atherosclerotic, antidiabetic, anti-inflammatory, and anti-neurodegenerative properties [1,5-9]. Recent studies have shown that persimmons are rich in flavonoids and terpenoids  with other compounds like tannins, coumarins, ionones, fatty acids and naphthoquinones [11-16]. The flavonoids like quercetin and iso-quercetin in PLE are responsible for their anti-inflammatory effects . These dietary flavonoids inhibit tumour necrosis factor-alpha (TNF-α) , vascular endothelial growth factor (VEGF)  interleukin-1beta (IL-1β), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) [19,20] that are known to be pro-inflammatory and pro-angiogenic cytokines. (D.Kaki)’s antioxidant activity is mainly linked to the presence of high molecular weight tannins that reduce the risk of cardiovascular diseases, hypertension, diabetes,and leukemia [21-23]. Along with that, terpenoids present in PLE
are reported to suppress stimulus-induced superoxide generation
and tyrosyl phosphorylation . Antioxidant and antiinflammatory
properties of PLE are crucial to maintain eye health.
So, many researchers are interested in PLE to check its effects on
different eye diseases. The eye is the one’s window to the outside
world and it is the most sensitive organ of the human body. Among
two important parts of the eye, the cornea is a clear front of the
eye while the retina is located at the back. The cornea controls and
focuses the light that enters the eye. The retina is a nerve layer
at the posterior part of the eye that detects light and generates
electrical impulses that are transmitted to the brain via the optic
nerve . The retina is made up of millions of light-sensitive cells
called rods and cones that help to convert light into signals that
the brain perceives as images. Any changes or disruption in the
function of the cornea or retina can cause serious damage.
In the recent past, many scientists have tried to use PLE
for different eye diseases like dry eye disease (DED), corneal
neurovascularization (CoNV), glaucoma, age-related macular
degeneration (AMD), diabetic retinopathy (DR), and edema.
So, the purpose of this review was to evaluate pharmaceutical,
medicinal and ethnopharmacological applications of PLE for eye
diseases. We expect that with more detailed investigations and
clinical trials, the PLE can be a potential drug against different
Oxidative stress refers to cellular and molecular damage
caused by reactive oxygen species (ROS). It has a major
contribution in corneal as well as retinal diseases. Oxidative
stress leads to ocular aging process and initiate or develop corneal
injury . Many corneal dystrophies are linked to oxidative
stress. Oxygen is continuously required during the visual process
. The retina, which is made up of specialized neurons and
retinal ganglion cells, is one of the body’s most oxygen-consuming
tissues (RGCs) . High oxygen consumption causes oxidative
stress-induced retinal damage and induces a high risk of ROS
accumulation in the retina which in turn raise a potential risk for
retinal disorders or retinal damage [29-32]. It is already reported
that patients with retinal degenerations exhibit high ROS levels
vs low levels of anti-oxidative proteins compared to healthy
patients . Antioxidants are long been used and prescribed for
better eye health  and are associated with a reduced risk for
developing retinal degeneration .
Ocular inflammation is considered one of the leading factors
for visual impairment. Some corneal  and most of the retinal
disorders are linked to inflammation [37-40]. Despite significant
progress in clinical care and understanding pathophysiological
mechanisms, there is still a significant unmet medical need relating to ocular disorders. Many antioxidants and anti-inflammatory
drugs are being used to treat these disorders but most of them
are coupled with multiple side effects. So, there is a dire need to
develop some drugs that can protect the eye without any harm.
Recently, different groups of scientists have studied the effect
of PLE on the different eye diseases. Here, we will briefly discuss
the eye diseases (DED, CoNV, AMD, DR, edema and glaucoma) and
the role of PLE as potential drugs.
With each blink of eye, tears spread on the cornea to provide
lubrication and wash off any foreign object to keep the eye clean.
DED is a serious condition that develops if a person doesn’t have
enough quality tears to lubricate the cornea. It is an inflammatory
condition with many resemblances to autoimmune diseases
[41,42] that is a common problem of all ages. DED is characterized
by inflammation of the ocular surface and lacrimal glands along
with symptoms of discomfort, visual disruption and tear film
instability . Inflammatory cytokines are increased in DED
conditions  that triggers apoptosis and apoptotic cells are
found in dry eye animal models [45,46]. So, DED can be treated
by inhibiting corneal inflammation . Commonly used ocular
drugs are unable to provide immediate and complete relief. Based
on data from the National Health and Wellness Survey, 6.8 per
cent of the United States adult population (approximately 16.4
million people) have been diagnosed with DED. PLE application
regulated the key factors for the healthy eye like tear volume, tear
breakup time (TBUT) and corneal epithelium lining in the dry eye
mouse model. There were less apoptotic cells and the expression
levels of apoptosis inducing inflammatory cytokines (IL-1α, IL-1β,
TNF-α, MCP-1, and IL-6) were also decreased. So, PLE treatment
not only helps the cornea to survive against degradation but also
help cells to proliferate in a regular manner .
CoNV is defined as the invasion of new blood vessels
into the cornea and occurs as a result of inflammation of the
cornea or imbalance between angiogenic and anti-angiogenic
factors [49-52]. Under inflammatory conditions, corneal cells
produce angiogenic factors like VEGF , which upregulates
the production of MMPs [54,55] and stimulates blood vessel
formation. The CoNV disrupts the corneal clarity leading to vision
loss in many cases. Anti-inflammatory, anti-VEGF agents and MMP
inhibitors are long been used to treat CoNV. All these drugs proved
beneficial for a short period and has severe side effects . When
PLE was applied to the injured eye representing CoNV eye model,
the protein expression level of angiogenic and inflammatory
proteins (VEGF, MMP, IL-6, FGF) decreased significantly . It is
reported that the flavonoids could be the active compounds that
exert these anti-inflammatory and anti-angiogenesis effects .
Another lethal ocular disorder is glaucoma that affects the
optic nerve , which is made up of a bundle of Retinal Ganglion
cells (RGC) axons in the retina. The main cause of glaucoma is the
flushing of aqueous humour that leads to increased intraocular
pressure (IOP) [60,61]. One of the obstacles in preventing the
etiology of glaucoma is protecting RGCs, and significant efforts
have been made in scientific and clinical research to minimize RGC
degradation . PLE is shown to reduced IOP . The studies
show that PLE reduce glaucoma symptoms in animal models of
glaucoma and play a protective role against RGCs death through
its anti-oxidative and anti-inflammatory properties .
AMD is known to be one of the leading cause of retinal
degeneration and blindness . It is a multifactorial disease
including aging, environmental factors and genetic susceptibility
. Chorionic inflammation and oxidative stress are known
to be the root cause of AMD and vision loss worldwide .
Antioxidants are long been used to treat retinal disorders .
D.Kaki fruit and leaves was proven to have antioxidant activities
[21,68]. So, when PLE applied to the mouse model that represent
retinal degeneration it ameliorates the symptoms .
DR is an inflammation of macula triggered by blood-retinal
barrier (BRB) breakage in diabetic patients . Oxidative stress
because of ROS accumulation and inflammatory cytokines plays
a major role in pathogenesis of DR [71-73] The studies have
demonstrated that SPARC-like protein 1 precursor (SPARCL1) is
overexpressed in DR [74,75]. However, downregulation of this
protein was observed in diabetic patients treated with PLE .
So, probably, PLE can be treated against DR disease
Corneal edema also known as the swelling of cornea it
occurs because of fluid buildup in cornea. It results in loss of
transparency and known to be the sign of acute corneal disorders.
Damage of corneal epithelium or endothelium contributes to this.
Ouabain (OU), a known Na+ /K+ -ATPae inhibitor, is reported to
causes edema in human and rabbit eye models [77,78]. When PLE
was applied to cells under the influence of OU, enzymatic activity
and protein level of Na+ /K+ -ATPae was increased . IOP also
contributes to corneal edema [80,81], and a recent study showed
PLE as an IOP lowering agent . All these above-mentioned
diseases seriously damage the eye. It is critical to diagnose the
factors contributing to these conditions to treat them for the sake
of healthy vision. So, the studies discusses here demonstrate that
PLE can be a potential agent to prevent many corneal and retinal
It can be concluded from this review that PLE has the potential
to be a candidate for the treatment of ocular diseases like DED,
CoNV, glaucoma, AMD, DR and edema. However, further detailed
studies including the identification of specific compounds
responsible for these effects as well as the clinical trials on all age
groups are needed before using PLE as an ocular drug.
Guo L, Moss SE, Alexander RA, Ali RR, Fitzke FW (2005) Retinal ganglion cell apoptosis in glaucoma is related to intraocular pressure and IOP-induced effects on extracellular matrix. Investigative ophthalmology & visual science 46(1): 175-182.
Neuburger M, Maier P, Böhringer D, Reinhard TJFJ (2013) The impact of corneal edema on intraocular pressure measurements using goldmann applanation tonometry, Tono Pen XL, iCare, and ORA an in vitro model. Journal of glaucoma 22(7): 584-590.