An In-Depth
Investigation of Diverse Therapeutic Benefits of Psidium guajava with
Major Emphasis on Anti-Diabetic effect
Betsy Sunny1*, Dr.
Manju Maria Mathews2, Dhanish Joseph3, Flowerlet Mathew4,
Junia George5, Bimi Varghese6
1,5,6Department of
Pharmaceutics, Nirmala College of Pharmacy, Muvattupuzha,
Kerala
2Associate
Professor, Department of Pharmaceutics, Nirmala College of Pharmacy, Muvattupuzha, Kerala 3,4Assistant
Professor, Department of Pharmaceutics, Nirmala College of Pharmacy, Muvattupuzha, Kerala *Corresponding
Author E-mail: betsysunnye@gmail.com
ABSTRACT:
Herbal remedies, or
phytotherapy, is the science of using herbal medicines to treat the sick.
Natural herbs are the highly esteemed source of medicine throughout human
history. Psidium guajava (PG), the common Guava tree popularly known as
'poor man's apple of the tropics is an important dietary plant having a long
history of traditional use for a wide range of ailments. The medicinal
properties of guava fruit, leaf and other parts of the plant are also well
known in the indigenous system of medicine. In view of the immense medicinal
importance of PG, this study reveals the efficacy of PG in the amelioration of
diabetes, a chronic metabolic disorder that affects the body's ability to
produce or use insulin. Treatments could be achieved by the use of synthetic
oral hypoglycaemic agents. But due to the major to minor side effects that have
been reported so far there is a persistent need to search for safe and
effective alternatives.
KEYWORDS: Psidium guajava,
Diabetes, Chronic metabolic disorder, Oral hypoglycaemic agents, Herbal
medicine.
INTRODUCTION:
The Allopathic drugs are often
limited in adequacy, carry the risk of unwanted effects, and are often
expensive. Whereas herbs represent a vast source of potentially useful dietary
supplements for improving blood glucose control and preventing long-term
complications in type 2 diabetes mellitus3. Thus the aim of this
work is to summarize the studies conducted on both in-vivo as well as
in-vitro biological activities of Psidium guajava (PG) by various
researchers based on a comprehensive review of pieces literature.
METHODOLOGY:
Data from various articles
both review as well as research articles were collected from various Databases
such as Google Scholar, Pubmed, and Science direct on the different in-vivo
and in-vitro studies of PG. Gone through the articles in detail and a
better understanding of the various activities with major emphasis on
anti-diabetic studies was made.
Plant Description:
Guava is a low evergreen tree
or shrub of 6 to 25 feet high, with wide-spreading branches and square, downy
twigs, is indigenous to tropical America. It is a usual vegetation cover by
roads and in waste places in Hawaii. Guava is a tropical and semitropical
plant. It is well known in the islands for its edible fruit. It is common in
the backyards. The branches are crooked, bringing opposite leaves. The flowers
are white, incurved petals, 2 or 3 in the leaf axils, they are fragrant, with
four to six petals and yellow anthers. The fruit is small, 3 to 6 cm long,
pear-shaped, reddish-yellow when ripe.4
Table No.1 Scientific
Classification of Psidium guajava5
|
Taxonomy |
Nomenclature |
|
Kingdom |
Plantae |
|
Division |
Magnoliophyta |
|
Class |
Magnoliopsida |
|
Subclass |
Rosidae |
|
Order |
Myrtales |
|
Family |
Myrtaceae |
|
Subfamily |
Myrtoideae |
|
Tribe |
Myrteae |
|
Genus |
Psidium |
|
Species |
Psidium guajava |
Chemical Constituents7:
Guava hold in a wide range of
phytochemicals including polysaccharides, vitamins, minerals, essential oils,
amino acids, proteins, enzymes, sesquiterpenoid alcohols, triterpenoid acids,
aromatic esters, alkaloids, glycosides, flavonoids, tannins, and saponins. It
is rich in antioxidants and vitamins, high in lutein, zeaxanthin and, lycopene.
It also contains ample amounts of tannins, phenols, triterpenes, flavonoids,
essential oils, saponins, carotenoids, lectins, vitamins, fiber, and fatty
acids. Fruit comprises of vitamin C and contains appreciable amounts of vitamin
A as well. Guava fruits are also a good reservoir of pectin - a dietary fiber.
Leaves are a rich source of flavonoids, in particular, quercetin. Much of
guava's healing potential is attributed to these flavonoids. And the flavonoids
have demonstrated antibacterial activity. Quercetin is thought to contribute to
the antidiarrheal effect of guava; it is able to relax the intestinal smooth
muscles and inhibit bowel contractions.
Table No.2 Nutritional profile of Psidium guajava fruit6
|
Nutrient |
Amount |
|
Vitamin G4 |
36-50 mg |
|
Calories |
77-86 g |
|
Moisture |
2.8-5.5 g |
|
Crude fibre |
0.9-1.0 g |
|
Protein |
0.1 - 0.5 g |
|
Fat |
0.43-0.7 g |
|
Ash |
9.5-10 g |
|
Carbohydrates |
9.1-17 mg |
|
Calcium |
17.8-30 mg |
|
Phosphorus |
0.30-0.70 mg |
|
Iron |
200-400 I.U. |
|
Carotene (vitamin A) |
0.046 mg |
|
Thiamine |
0.03-0.04 mg |
|
Riboflavin |
0.6-1.068 mg |
|
Niacin |
40 I.U. |
|
Vitamin B3 |
35 I.U. |
Anti-Diabetic Activity of Psidium
guajava:
PG has traditionally been used
for the treatment of diabetes. The antihyperglycemic activity of the various
parts of PG carried out in-vivo are being discussed in the table below.
Three types of leaf extracts
are being mentioned in the table above. The solvents used for extraction is
different in three of the cases. All the extracts were tested on male Wistar
rats of almost the same body weight and are compared with the activity of the
standard.
Improved levels of plasma
Insulin and Haemoglobin by leaf extract of Psidium guajava:
In the study conducted on
antidiabetic and antioxidant potential of PG leaves, in streptozotocin-induced
diabetes in rats mentioned in the oral administration of PG leaf extract (300
mg/kg body weight/day) for 30 days to streptozotocin-induced diabetes rats
significantly decreased the levels of blood glucose, glycosylated haemoglobin
and improved the levels of plasma insulin and haemoglobin (Table No.3).
Table No. 3 In -Vivo Anti Diabetic Activity of Leaf Extracts of Psidium
guajava
|
Plant part |
Extraction method |
Treatment |
Animal/ induction method |
Dose |
In-vivo response |
Reference |
|
|
Glucose level |
% Reduction |
||||||
|
Leaf extract |
500 mL of petroleum ether 60-80°C, 500 ml 95% ethanol |
30 Days |
Male Wistar albino rats, wt: 160-180 g, STZ: 50 mg/kg, 10% glucose, 6 animals |
300 mg/kg |
98.31 ± 7.07 |
68.04 |
S. Subramanian et al., 3 |
|
Gliclazide: 5 mg/kg |
107.62 ± 7.2 |
65.05 |
|||||
|
Diabetic control |
307.62 ± 24.9 |
- |
|||||
|
Control |
91.84 ± 5.42 |
- |
|||||
|
Leaf extract |
Distilled water, dried at 30° C |
30 Days |
Adult male Wistar albino rats, wt: 120-150 g, STZ: 60 mg/ kg, 6 animals |
500 mg/ kg |
127.33± 2.027 |
64.59 |
Shadia Ali Radwan et al., 8 |
|
Glibenclamide : 5mg/kg |
156.5± 1.47 |
56.96 |
|||||
|
Leaf extract 500 mg/kg+ Glibenclamide 5 mg/kg |
112.33± 1.429 |
68.76 |
|||||
|
Diabetic control |
359.67± 2.17 |
- |
|||||
|
Control |
110 ± 1.39 |
- |
|||||
|
Leaf extract |
98% ethanol |
9 Hour |
Male Wistar rats, wt : 180 ±10 g , alloxan :(100 mg/kg i.p.), 5 rats, 3 group |
750 mg/kg |
7.22±0.53 |
75.12 |
Santosh Mazumdar et al., 9 |
|
Glibenclamide : 4.15 mg/kg |
5.36 ± 0.59 |
81.53 |
|||||
|
Diabetic control |
29.03±1.81 |
- |
|||||
|
Control |
6.14±0.22 |
- |
|||||
STZ: Streptozotocin
Even though the variation is
less the leaf extract has shown a more reduction in the blood glucose level as
compared to the Standard drug; Gliclazide. The % reduction of the blood glucose
level of leaf extract has shown an increase of three times compared to the
standard. When compared with the blood glucose level of the Diabetic control a
significant reduction in the blood glucose level can be noticed in the case of
the petroleum ether and ethanolic leaf extract of PG. The levels of protein,
urea, creatinine, non-enzymatic antioxidants, and the activities of enzymatic
antioxidants such as superoxide dismutase, catalase, glutathione peroxidase,
and glutathione S-transferase were also markedly altered in the liver of
STZ-induced diabetic rats. Oral administration of PG for 30 days restored all
these biochemical parameters to near control levels.
Improvement of Liver and
Kidney Functions by leaf extract of Psidium gujava:
Anti-diabetic effect of
aqueous extract of guava leaf using rat model of diabetes induced by
streptozotocin was investigated by Shadia Ali Radwan et al. (Table No.3). In
addition, the effect of this extract on liver and kidney functions induced in
the rat model of diabetes were investigated. Rats were divided randomly into
control group, rat model of diabetes induced by streptozotocin, rat model of
diabetes treated with aqueous extract of guava leaf, rat model of diabetes
treated with Glibenclamide and rat model of diabetes treated with aqueous
extract of guava leaf plus Glibenclamide. Aqueous leaf extract was given at a
dose of 500mg/kg. Standard used here is Glibenclamide 5mg/kg. Diabetes was
induced using Streptozotocin 60 mg/kg. The least blood glucose level was shown
by the control which is a noticeable fact. The next least blood glucose level
was exhibited by the leaf extract and Glibenclamide combination followed by the
leaf extract and then the Standard. But coming to the % reduction of glucose
Glibenclamide has shown the highest reduction followed by the leaf extract and
finally the leaf extract and Glibenclamide combination. Streptozotocin-induced
a significant increase in the activities of Aspartate aminotransferase (AST),
Alanine aminotransferase (ALT), Alkaline phosphatase (ALP) and a
significant increase in the levels of bilirubin, urea, creatinine and uric
acid. In addition, histopathological and immunological changes were detected in
the pancreatic tissue. In this rat model of diabetes, a significant decrease in
the serum insulin level and a significant increase in glucose level were
detected. But the result data revealed that aqueous extract of guava leaf improved
the reduced insulin level and the high glucose level induced by streptozotocin.
This was associated with an improvement in the changes in the liver and kidney
functions. Loss of body weight gain induced by streptozotocin was alleviated by
guava leaf extract, glibenclamide or both. The duration of treatment was 30
days.
Stimulation of glucose
metabolic enzymes in Liver tissues by Psidium guajava leaf extract:
When PG leaf was extracted
with 98% ethanol and administered at a dose of 750mg/kg has shown a reduction
in the blood glucose level of 75.12% (Table No.3) as leaf extract might have
stimulated glucose metabolic enzymes in liver tissues. Standard drug
Glibenclamide was given at a dose of 4.15mg/kg. Here Diabetes was induced with
Alloxan Monohydrate 100 mg/kg. Though the blood glucose levels were found to
have only the least difference the % reduction was found to be higher for the
standard.
The order of glucose reduction
of the leaf extracts as per (Table No.3) is as follows: Ethanolic leaf extract of
PG 750mg/kg > petroleum ether and ethanolic leaf extract 300mg/kg >
aqueous leaf extract 500 mg/kg.
Antidiabetic potential of
Lanostene-type triterpenoids of leaves of Psidium guajava:
As leaf extract has proven to
have antidiabetic activity the constituents present in the leaf may also
possess antidiabetic effect. Thereby a review was made on the study conducted
by Priyanka Bagri et al., on Lanostene-type triterpenoids from leaves of PG
(Table No.4). The constituents were extracted using 250ml methanol, silica gel,
petroleum ether, chloroform, and the study was conducted for 7 days on male
albino Wistar rats. Streptozotocin 60mg/kg was used to induce diabetes. Four
types of Lanostenoids were tested at the same dose of 50mg/kg and compared with
the control. Trihydroxypsidiumlanostenoic acid (50mg/kg/day) has shown the
least glucose level of the four Lanostenoids.
Table No.4 Lanostenoids From Leaves
|
Plant part |
Extraction method |
Treatment |
Animal/ Induction method |
Dose |
Glucose Level |
Reference |
|
Lanostenoids from leaves |
250 ml methanol, silica gel, petroleum ether, chloroform |
7 Days |
Male Albino Wistar rats (150-200 g), STZ: 60 mg/kg, 6 rats, 6 group |
Psidiumlanostenoic acid (50 mg/kg/day) |
100.67 ± 10.71 |
Priyanka Bagri et al., 10 |
|
12β-Hydroxypsidiumlanostenoi c acid (50 mg/kg/day) |
87 ± 11.78 |
|||||
|
Trihydroxypsidiumlanostenoic acid (50 mg/kg/day) |
84.50 ± 12.42 |
|||||
|
Psidiumlanostenoic acid glucoside (50 mg/kg/day) |
90.33 ± 12.88 |
|||||
|
Control |
90.34 ± 8.89 |
Table No.5 Other Parts of Psidium
guajava with Anti -Diabetic Effect
|
Plant part |
Extraction method |
Treatment |
Animal/ induction method |
Dose |
In-vivo response |
Reference |
|
|
Glucose level |
% reduction |
||||||
|
Unripe fruit peel extract |
Hot water, 48 hr |
21 Days |
Male albino Wistar rats, 6-8 week old, 150-200 g, STZ: 45 mg/kg wt, 6 rats, 5 group |
400 mg/kg |
255.7 ± 6.8 |
21.78 |
Prashant K. Rai et al., 11 |
|
Diabetic control |
326.9 ± 6.8 |
- |
|||||
|
Stem bark extract |
Ethanol (95%) |
3 Hour |
Wistar rats (180–200 g) of either sex, alloxan:120 mg/kg, 5 animals, 3 group |
250 mg/kg |
223.4 ±2.60 |
36.02 |
H.M. Mukhtar et al., 12 |
|
Gliclazide |
308.2 ±2.522 |
11.74 |
|||||
|
25 mg/kg |
|||||||
|
Diabetic control |
349.2 ± 2.08 |
- |
|||||
Table No.6 In-Vitro Antidiabetic Activity of Leaf Extract of Psidium
guajava
|
Plant part |
Extraction method |
Experimental model |
Dose |
Movement of glucose out of dialysis tube (mg/dl) |
Reference |
|
Leaf extracts |
Ethyl acetate, n-hexane, ethanol, methanol, petroleum ether, and chloroform: Continuous percolation |
Dialysis tube: plant extract, CMC, Sodium chloride containing D-glucose, 27 hr incubation period |
n-Hexane extract (50g/l) |
301.26±1.86 |
Sabjan Khaleel Basha et al., 13 |
|
Ethanol extract (50g/l) |
260±1.62 |
||||
|
Methanol extract (50 g/l) |
201±1.69 |
||||
|
Aqueous extract (50 g/l) |
212.11±1.44 |
||||
|
Control |
3142±289 |
Psidiumlanostenoic acid
glucoside (50mg/kg/day) has shown a result comparable with control. The study
concluded that the leaves of PG possessed antidiabetic lanostene-type
triterpenoids. The order of reduction of blood glucose levels by the various
lanostenoids is: Trihydroxypsidiumlanostenoic acid (50mg/kg/day)
>12β-Hydroxypsidiumlanostenoic acid (50mg/kg/day) >
Psidiumlanostenoic acid glucoside (50mg/kg/day) >Psidiumlanostenoic acid
(50mg/kg/day).
Other parts of PG like the
fruit as well as stembark also possess antidiabetic property that was proven
from the above studies conducted on the unripe fruit peel extract and stembark
extract.
Glycemic potential of aqueous
extract of Psidium guajava unripe fruit peel:
When the unripe fruit peel of
PG was extracted using hot water for 48 hrs and given to albino rats at a dose
of 400 mg/kg, a reduction in the blood glucose level of 21.78 % was observed
(Table No.5). The duration of the study was 21 days. Streptozotocin was induced
at a dose of 45 mg/kg. Blood glucose levels were measured by the glucose
oxidase method.
Enhancement of peripheral
metabolism of glucose by Stem bark extract of Psidium guajava:
The stem bark of PG after
extraction with ethanol 95% and administered at a dose of 250mg/kg, a 36.02%
reduction in the blood glucose was observed (Table No.5). It was compared with
Gliclazide 25mg/kg and the significant reduction was shown by stem bark extract
25 mg/kg. Oral administration of the ethanol extract led to significant blood
glucose lowering effect in alloxan-induced hyperglycemic rats. The fall was
seen at 1 hour and remained up to 3 hours after the administration of the
extract whereas the fall in case of Gliclazide administration was marginal.
This may be due to the fact that alloxan treatment causes permanent destruction
of the β-cells and Gliclazide requires more than 30% functional pancreas
for the effect. The hypoglycaemic activity of PG stem bark could be due to an
enhancement of peripheral metabolism of glucose.
Improvement in Body weight and
Lipid profile by Seed extract of Psidium guajava:
A study on the seed extracts
of PG done by Kanakam Vijayabhaskar et al.,7 " Evaluation of
anti-diabetic activity on guava seeds aqueous extract in streptozotocin-induced
diabetic rats" the effect of aqueous and cold extracts of PG seeds, on
fasting blood sugar levels and serum biochemical analysis in
streptozotocin-induced diabetic rats was investigated. All the extracts of PG
produced a significant antidiabetic activity at dose levels of 1/5th of their
lethal doses. These extracts also showed improvement in parameters like body
weight and lipid profile as well as regeneration of β-cells of the pancreas.
Inhibition of Glucose
Diffusion by various leaf extracts of Psidium guajava:
In the in-vitro study to
evaluate the glucose uptake of crude n-hexane, ethanol, methanol and aqueous
leaf extracts of PG all the extracts were subjected to the inhibitory effect of
glucose utilization using specific standard in vitro procedure and were tested
at the same doses of 50g/l (Table No.6). Duration of the study was 27 hours. Of
all the extracts being tested the methanolic extract was found to be more
potent than other extracts with the lowest mean glucose concentration of
201±1.69 mg/dl.
Other Pharmacological Actions
of Psidium guajava:
Antioxidant Activity:
A comparison on the
antioxidant activity and free radical scavenging effects of extracts of guava
leaves and dried guava fruit were done by Hui-Yin Chen and Gow-Chin Yen S. The
inhibition of linoleic acid oxidation was 94.4-96.2% in a concentration of 100 mg/ml.
The results prove that the scavenging effect of ABTS and superoxide anion is
increased with the increasing concentration of guava leaf extracts. The
antioxidant activity may be due to the blocking of chain reaction by the
linoleic acid.14
Cardioprotective Effect:
Studies conducted by S
Yamashiro et al., showed that the aqueous leaf extract of PG exhibited
cardioprotective effects against myocardial ischemia-reperfusion injury in
isolated rat heart. Elevation of endogenous antioxidants, retention of the
myocardial antioxidant status and appreciable restoration of most of the varied
hemodynamic parameters may have contributed to its cardioprotective effect.15
Another investigation by Gondim Antonio showed that aqueous fractions collected
from the acetic extract of PG leaf exhibit negative inotropic effect by
declining the atrial contractility by reduced calcium (Ca2+) entry in
myocardial cells and also by opening potassium channels of cardiac tissue.16
Anti
Inflammatory Activity:
A decoction of PG leaves was
used for the treatment of various inflammatory ailments including rheumatism.
Anti-inflammatory and analgesic effects of the leaf extracts of PG was due to
the presence of polyphenolic compounds and triterpenoids. Aqueous extract of PG
at a dose of 50-800mg/kg, i.p. produced dose-dependent and significant
inhibition of fresh egg albumin-induced acute inflammation (edema) in rats (JA
Ojewole).17 Further, leaf extract (50–800mg/kg, i.p.) also produced
dose-dependent and remarkable analgesic effects against thermally and
chemically elicited nociceptive pain in mice.
Anticancer
Effect:
Sang-Bong Lee et al., carried
out a study on the anticancer activity of guava branch extracts against HT-29
human colon cancer cells. The study established a program to screen natural
products for cytotoxic activity using the MTT reduction assay system to test
HT-29 human colon cancer cells. During the course of screening, they found that
the acetone extracts of guava branch (GBA) had cytotoxic effects on HT-29
cells. The GBA showed highly cytotoxic effects through MTT reduction assay, LDH
release assay, and colony formation assay. In particular, the GBA of the
250µg/ml showed 35.5% inhibition against the growth of HT-29 cells. As
expected, GBA induced characteristic apoptotic effects in HT-29 cells,
including chromatin condensation and sharking that occurred 24 hours after the
cells had been treated at a concentration level of 250µg/ml. To examine the
functions on apoptosis, they used a flow cytometric analysis. The apoptotic
cells were distributed according to the cell cycle phase shown by sub-G1 DNA
content.18
Antitussive
Activity:
According to Jaiarj P et al.,
the water infusion from PG leaves decreased the frequency of coughing induced
by capsaicin aerosol as compared to the control, within10 minutes after
injection of the extract. These results suggest that guava leaf extract could
be recommended as a cough remedy.19
Hepatoprotective
Activity:
The aqueous leaf extract of PG
has been reported for their hepatoprotective action at a dose of 500mg kg-1
by CK Roy et al.,20 Studies conducted by J Gao et al.,
indicated that the Asiatic acid which is present in the leaves and fruit of PG
is responsible for the hepatoprotection.21 According to G Tajua et
al., PG leaf extracts (500mg/kg, PO) significantly reduced the elevated serum
levels of aspartate aminotransferase, alanine aminotransferase (AAT), alkaline
phosphatase, protein and bilirubin, some antioxidant enzymes, Reduced
glutathione (GSH), GPx, SOD and CAT activities, were also evaluated in the rats
liver homogenate. The higher dose of the extract (500mg/kg, p.o) prevented and
showed an increase in liver weight while the lower dose was ineffective in the
paracetamol-induced liver damage. In the acute liver injury induced by
paracetamol the higher dose (500mg/kg, p.o.) of PG leaf extract was found to be
more effective than the lower dose (250mg/kg, p.o.).22 Studies by
Prashant Rai Kumar et al., showed that the unripe fruit feel of PG has a potent
hepatoprotective agent.23,27
Miscellaneous
Activity:
Leaf extract of PG is reported
in the Acne vulgaris, a chronic inflammatory disease involving colonization of
Propionibacterium acnes, plus activation of neutrophils and lymphocytes by F
Qadan et al..24 PG leaf extracts have potent antimicrobial
activities against Propionibacterium acnes and may be beneficial in treating
acne especially when they are known to have anti-inflammatory activities. Also,
the aqueous leaf extract of PG has been reported (FA Razak et al., ) to be
effective against dental caries and helpful in reducing dental plaque caused by
Staphylococcus sanguinis, Staphylococcus mitis, and Actinomyces sp. at a dose
of 1mg/ml.25 Guava stem bark and leaf stem extract has been found to
possess antigiardiasis activity and inhibit the growth of Entamoebahistolytica
by MM Ponce et al., respectively.26
A-Petroleum ether
ðanolic leaf extract 300 mg/kg, B- Aqueous Leaf extract 500 mg/kg,
C-Ethanolic leaf extract 750 mg/kg , D- Aqueous unripe fruit peel extract
400mg/kg, E- Ethanolic stem bark extract 250 mg/kg, F- Leaf extract 500mg/kg
+Glibenclamide 5 mg/kg, G- Gliclazide 5 mg/kg , H- Glibenclamide - 5mg/kg,
I-Glibenclamide 4.15 mg/kg, J-Gliclazide 25 mg/kg .
Figure 1. % Glucose reduction
of different parts of Psidium guajava
RESULTS AND DISCUSSION:
Based on the data above every
part of PG such as the leaf, fruit, bark, and seed possess antidiabetic
activity. The studies conducted on the leaf extracts was comparatively more
than those of the other parts which undoubtedly provides an idea that leaves
are having the best antidiabetic activity than other parts. Leaves were
extracted using different solvents such as Petroleum ether, ethanol, water etc.
All the parts were used in the form of extracts.
From the results obtained a %
Glucose reduction VS Dose graph can be plotted. The parts, solvents used for
extraction and the doses are given on the X-axis whereas the % Glucose reduction
on the Y-axis.
A to E are the various plant
part extracts and F to J are the different Standard drugs used.
From the graph, it
is clear that the most potent activity had been shown by (I) Glibenclamide
4.15mg/kg, the standard. 4.15 mg/kg is the least dose of Glibenclamide
mentioned in the studies and the second potent activity was shown by the
Ethanolic leaf extract 750mg/kg. A combination of the leaf extract and
Glibenclamide are also plotted in the graph (F). Of the various parts of PG,
leaf extract was found to have the best anti-diabetic potential. From the leaf
extracts, ethanolic leaf extract (750mg/kg) was found to be more potent. The
potent antihyperglycemic effect of guava leaf extract could be due to its
ability to promote glucose uptake by liver and other peripheral tissues
together with the inhibition of intestinal glucose absorption induced by guava
leaf extract.8 Aqueous unripe fruit peel extract has shown the least
glucose reduction amongst the other parts. Of the different standards mentioned
to have used in the studies, Glibenclamide 4.15mg/kg was found to be the best.
So it can be concluded from the graph that in the case of standard drug, the
least dose provides the most potent activity whereas opposite is the case of
the extract that is, the highest dose among the extracts showed the most potent
activity. Therefore in the case of standard, a low dose is sufficient to
provide a marked reduction in the blood glucose level, but for extracts an
increase in the dose resulted in a simultaneous increase in activity. The very
less activity was shown by Gliclazide 25 mg/kg.
In addition to
antidiabetic activity, many pharmacological studies have demonstrated the
ability of this plant to exhibit antioxidant, hepatoprotective, antimicrobial,
cytotoxic, antispasmodic, cardioactive, anticough, and anti-inflammatory
activities, supporting its traditional uses.
Diabetes is a long-term
disease with variable clinical manifestations and progression, chronic
hyperglycemia from whatever cause leads to a number of complications including
cardiovascular such as hypertension, renal, neurological such as anxiety,
stress, ocular and other such inter-current infections. As diabetes is
characterized by defects in both metabolic and vascular domains, this disease
represents a privileged situation for oxidative stress exerting harmful
effects.28 Diabetes adds to the many environmental causes, which are
common to many diseases, some extremely active sources generating reactive
oxygen species (ROS) as a consequence of high glucose but also, as will be
seen, and several other factors.29 Under diabetic conditions,
induced oxidative stress also activates the JNK pathway, which is involved in
the deterioration of pancreatic β-cell function found in diabetes. There
are several novel approaches which might cure diabetes. Defective
glucose-stimulated insulin secretion by pancreatic islet β cells could be
cured with recombinant glucagon-like peptide 1 (GLP-1) or agonists of the GLP-1
receptor. The role of peroxisome proliferator-activated receptors (PPAR γ)
in the regulation of lipid metabolism, insulin and triglycerides lead to the
rational design of several PPAR agonists. Gene therapy also generates greater
hope for a possible cure for diabetes. Sodium-Glucose Co-Transporter inhibitor
is also one of the novel targets for lowering plasma glucose and improving
insulin resistance by increasing renal glucose excretion. Treatment with
antioxidants and/or suppression of the JNK pathway protect β-cells from
some of the toxic effects of hyperglycemia could be the one of novel target
therapy of diabetes mellitus.30 Nanotechnology could be made use of
in the treatment of diabetes. The stomach acid destroys protein-based Insulin.
Diabetic patients control their blood-sugar levels via insulin introduced
directly into the bloodstream by injections which is very painful. The new
system is based on inhaling the insulin and on a controlled release of insulin
directly into the bloodstream. Such kind of treatment for diabetes includes the
proper delivery of insulin in the bloodstream it can be achieved by
nanotechnology by the development of oral insulin.31 The thiazolidinediones
used in oral combination therapy in the management of patients with type II
diabetes who have insufficient glycaemic control despite a maximally tolerated
dose of oral mono-therapy with either metformin or sulphonylurea.28
Diet therapy is the cornerstone for the management of gestational diabetes
mellitus. Although there is widespread use of herbal dietary supplements that
are believed to benefit type 2 diabetes mellitus, few have been proven to do so
in properly designed randomized trials.32
Herbal remedies could provide
improved adherence to patients than conventional oral hypoglycemic agents. The
quality of herbal drugs is the sum of all factors which contribute directly or
indirectly to the safety, effectiveness, and acceptability of the product. A
system to ensure that every packet of medicine that is being sold has the
correct substances in the correct amount and will induce its therapeutic effect
this is known as standardization.33 The major hindrance in the
amalgamation of herbal medicines into modern medical practices is the lack of
scientific and clinical data and a better understanding of efficacy and safety
of the herbal products. It requires a thorough search for medicinal plants,
proper guidelines for their identification, validation of the scientific
methods of isolation of active ingredients, pre-clinical evaluation of their
pharmacological and toxicological profiles, and lastly, the clinical evidence
of their usefulness needs to be obtained.34 Other than PG there are
numerous other herbs which possess significant hypoglycemic effect. Some of
which includes; the methanolic extract of different parts of Coccinia grandis,35
the ethanolic fraction of Thuja occidentalis (EFTO) which exhibited significant
anti-hyperglycemic activities in alloxan-induced diabetic rats.36 This
extract has shown improvement in parameters like body weight and lipid profile
by enhancing the effect on cellular antioxidant defenses to protect against
oxidative damage. Alcoholic extracts of Sida cordifolia had more significantly
reduced the blood glucose level after a single dose and nearly equal to
standard glibenclamide after prolonged treatment. Al the extracts were given
orally at a dose of 250mg/Kg b.w.37 Nelumbo nucifera rhizome and
flower extract was found to be a promising antidiabetic agent in STZ induced
rats.38
CONCLUSION:
It is
evident from the Literature survey that the extracts from different parts of PG
possess excellent antihyperglycemic status. Of the several extracts, leaf
extract was found to be more potent. The presence of tannins, triterpenes, and
flavonoids in PG leaves may be partially responsible for its antidiabetogenic
properties. Moreover, guava is traditionally being used for the treatment of
several other ailments including Diarrhoea, Cough, Hypertension, Sore throat,
etc. It is also a digestive and carminative, gives vigor and strength to the
heart, lungs, and whole body. Toxicity studies in mice and other animal models,
as well as in controlled human studies, showed that both leaf and fruit are
safe without any adverse effects. Hence supplementing a balanced diet like
Guava health tea may provide health-promoting effects. "A Guava fruit a
day keeps a Doctor away"; therefore the future prospects should be aimed
at investigating the biodiversity of guava and/or the purification of the
different compounds present in guava in order to obtain functional ingredients
for additional uses as alternate agents in natural therapeutic approaches.
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Received on 04.03.2019
Modified on 10.04.2019
Accepted on 16.05.2019
© RJPT All right reserved
Research J. Pharm. and Tech.
2019; 12(10): 5029-5036.
DOI: 10.5958/0974-360X.2019.00873.4