Diabetes mellitus refers to a group of heterogeneous metabolic disorders primarily characterized by chronic hyperglycemia, defined as a persistent elevation in blood glucose levels. The primary cause is either a disruption in insulin secretion, varying degrees of insulin resistance, or, more commonly, a combination of both. Diabetes mellitus, if left untreated, inadequately treated, or
undiagnosed over a longer period, is most often correlated with the increased
risk of cardiovascular diseases, kidney disorders, blindness, and foot cutoff (1, 2). According to IDF (International Diabetes Atlas, 10th
edition), in the 21st century, diabetes is the fastest-growing
health emergency worldwide. It has been projected that about 643 million people
will have diabetes by 2030 and 783 million by 2045 (3). Diabetes mellitus substantially affects food nutrients such
as carbohydrate, fat, and protein metabolism and sequentially causes chronic
hyperglycemia followed by lipid profile abnormalities. Long-term untreated or
poorly treated hyperglycemia considerably induces numerous microvascular and
macrovascular diabetic complexities that are the ultimate reasons for diabetes-related
morbidity and mortality (4).
The accessible medications for diabetes
are insulin and varied oral antidiabetic agents like biguanides, sulfonylureas,
thiazolidinediones, non-sulfonylureas secretagogues, and α-glucosidase
inhibitors, etc., alongside insulin (5, 6). Therefore, these drugs are used as monotherapy or combined
to get better glycemic control and mask serious adverse effects of each oral
antidiabetic agent (7). Over the last few decades, numerous studies have been done to
find any potential in medicinal plants alone or a combination of oral
antidiabetic agents in improving hyperglycemia and associated complications of
DM in animal models (8). Plenty of
plants have been carefully evaluated as a primary origin of dominant
antidiabetic agents because herbal plants are a rich wellspring of
phytoconstituents with insignificant toxicity or no side effects, making them a
potential therapeutic choice for treating diabetes (9-11). Moreover, herbal medicine offers treatment at a
cheaper rate than conventional medicine (). An extensive review by Salehi et al. has
covered many medicinal plants claimed
to possess antidiabetic activity ().
Declarations
Acknowledgment
All authors are thankful to the Department of Pharmacy, Southeast University for providing all the support and equipment to conduct this research work. Special thanks to ICDDRB for providing experimental rats. Authors also thank the Bangladesh National Herbarium for identifying our experimental plants.
Conflict of Interest
The authors declare no conflicting interest.
Data Availability
The unpublished data is available upon request to the corresponding author.
Ethics Statement
All animal experiments were conducted in accordance with the approval of the Animal Ethics Committee of Southeast University, under notification letter number SEU/Pharm/CECR/122/2023.
Mentha
viridis (M. viridis), also known as Mentha
spicata or spearmint, is a medicinal plant member of the Lamiaceae family widely
grown in Europe, Asia, and North America but currently cultivated worldwide (12). This medicinal plant has many beneficial effects in its
phytoconstituents and is utilized in numerous disorders such as diabetes,
respiratory diseases, and skin disorders (13-15). According to Benkhnigue et
al., for diabetes therapy, the leaf of M.
viridis is orally given as a decoction in the locality of Al Haouz-Rhamna
in Morocco (16). In another study reported by Idm’ hand et al., the leaf and stem of M.viridis are used to treat diabetes as a decoction or infusion form (13). Aqueous ethanolic extract of M. viridis exhibited blood glucose lowering and hypolipidemic
effect in alloxan-caused diabetic rats (17). Additionally, aqueous leaf extract showed positive results
in hyperglycemia and lipid abnormalities in diabetic animals (18). Phenolic leaf extract of M. viridis had antidiabetic effects in chemically induced diabetic
rats, as reported elsewhere (19).
Notably, numerous studies reported that
preliminary screening of M. viridis disclosed
the existence of phytoconstituents, for example, tannins, polyphenols, steroids,
flavonoids, triterpenes, and glycosides (20). Per one study, ethanolic extracts of M. viridis contain a substantial amount of phenolic compounds,
including polyphenols, flavonoids, and caffeic acid derivatives (21). In essential oils extracted from M. viridis, carvone was an entire primary component besides
trans-carveol, limonene, linalool, menthone, piperitone, piperitone oxide, and isomenthone
(8). This research work was aimed to investigate the chemical
composition of the ethanolic extract of M. viridis and to evaluate the
antihyperglycemic and antihyperlipidemic activities of M. viridis separately and in blending with metformin in chemically
induced diabetic rats by alloxan.
Methods and Materials
Chemicals
All the chemicals employed in this investigation were of analytical
grade. Alloxan was bought from German-based Sigma Chemicals. Glucose was
procured from Glaxo Smith Kline. The rest of the chemicals, like triglycerides (TG), ligh-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC) kits, were obtained
from (LINEAR CHEMICALS S.L., Spain). The reference drug, metformin, was
purchased from Chadwell Health Essex, England. The required solutions were
prepared on each day of the experiment.
Plant Collection
Leaves
and barks of M. viridis were
collected from Kawranbazar, Dhaka 1215, Bangladesh. The whole
plant (leaves and barks) was identified by a Bangladesh National Herbarium
specialist in Mirpur, Dhaka, Bangladesh. The accession number is DACB–41939.
Extract Preparation
Leaves
and barks of M. viridis were
rigorously cleaned with water and afterwards dried for seven days under
sunlight. The coarse powder was obtained from the plant parts after grinding
with an appropriate grinder machine. The dried and powdered materials (100 g)
from each plant part were immersed in 500 mL of 90% ethanol for two weeks at
ambient temperature with periodic shaking. Initially, a cotton filter and
finally, a Whatman No. 1 filter paper were utilized to filter the solution. A
rotary evaporator from Bibby Sterlin Ltd, UK, concentrated the filtrate at
40°C. A semisolid extract (2.08 g each) was obtained when the extra solvent
evaporated.
Experimental Animal
Long
Evans male rats (100–120 g) aged nine weeks were obtained from the ICDDR, B
(International Centre for Diarrheal Disease Research, Bangladesh). The standard
atmospheric states, such as 22–25°C temperature, 60–65% humidity, light/dark
cycle (12/12 h), etc., were maintained when rats were kept in animal cases.
Throughout the experiment, all rats were given food like standard laboratory
diet (Purina rat chow) from ICDDR, B, Dhaka, and pure drinking water. All animal
experiments were performed after the agreement with the Committee of Animal Ethics
of Southeast University, Department of Pharmacy.
Acute Toxicity Studies
Long Evans male rats were fasted
overnight and were selected for the study. Each extract (whole plant and leaf
extract only) was administered orally to two groups (n = 5) of rats. The doses
were 250 mg/kgBW and 500 mg/kgBW (for whole plant and leaf
extract). Following administration of all the extracts and metformin, the
animals were perceived intimately, particularly for the initial three h,
for expression in abnormalities, such as salivation, surged motor activity, chronic
convulsions, coma, and death. Regular inspections were done at a uniform gap
for a single whole day. This regular monitoring was continued for 4 days.
Organizing of Investigational Rats
Long-Evans rats were arbitrarily allocated into 7 groups. Each
group contains five rats (n = 5) and utilized test studies, including the blood
glucose estimation, evaluation of lipid profile, etc., following 14-day
treatment protocols.
Group I: Healthy normal rats
with no treatment (Normal control)
Group II: Diabetic control
rats (Untreated Group) (Negative control)
Group III: Diabetic rats
administered leaf extract (500 mg/kgBW)
Group IV: Diabetic rats
administered herb extract (500 mg/kgBW)
Group V: Diabetic rats
administered metformin (850 mg/70 kgBW)
Group VI: Diabetic rats
administered a blending of leaf extract (250 mg/kgBW) and metformin (425 mg/70
kgBW)
Group VII: Diabetic rats
administered a blending of whole plant extract (250 mg/kgBW) and metformin
(425 mg/70 kgBW)
Diabetes Induction
A
newly prepared alloxan solution (120 mg/kgBW) in distilled water was injected
intraperitoneally singly into each rat after 12 h of overnight fasting. These
animals were given a 10% glucose solution to drink to deal with alloxan-induced
low blood sugar, as there was an instantaneous rise in blood insulin just after
the alloxan injection within minutes, called the initial transient hypoglycemic
phase (22,
23). Blood glucose content
was estimated from the tail vein of diabetic rats 72 h later. With marked
hyperglycemia (FBG (fasting blood glucose) ≥25.70 mmol/L were
chosen for the successive investigation.
Preparation of Dosage of Reference Drug and Plant Extract
Preparation
of Extract Solution (Leaf and Whole Plant)
The extracts (leaf and whole plants) were semisolid and sparingly
soluble in water. The suspension form of the water dosages was prepared so that
each 0.1 mL of solution contained plant extract as specified by the 500 mg/kgBW dose.
Preparation
of Metformin Solution
The physical appearance of metformin was a white crystalline solid
and was highly soluble in water. That’s why the dosages were prepared in
solution form using distilled water so that each 0.1 mL of solution contained metformin
following the dose of 850 mg/70 kgBW. In humans, this drug works effectively
in the same dose.
Preparation of Leaf Extract and Metformin Combination
The dosage was prepared individually so that each 0.1 mL of
solution contained leaf extract and metformin in line with the dose of 250 mg/kgBW
of leaf extract and 425 mg/70 kgBW of metformin in the given order.
Preparation of Whole Plant Extract and Metformin Combination
The dosage was prepared individually so that each 0.1 mL of solution
contained plant extract and metformin as per the dose of 250 mg/kgBW of plant
extract and 425 mg/70 kgBW of metformin in the order given.
Blood Serum Collection
Following the completion of the two weeks of treatment with the
drug and extracts (whole plant and leaf), chloroform was employed to
anesthetize the rats. After confirming that the rats had become unconscious, the
thoracic artery was opened by cutting their abdominal skin. 3–4 mL of blood
collected directly from the thoracic artery by syringe immediately after
opening their skin. The blood sample was centrifuged at 4000 rpm (rotate per
minute) for 20 min using a centrifuge machine (Digisystem Laboratory
Instrument Inc. Taiwan). The supernatant plasma samples were decanted and
stored at -4°C until biochemical examinations were done.
Lipid
Profile
Lipid profile parameters like TC, TG, HDL-C, and LDL-C were
estimated colorimetrically by a hematology analyzer using wet reagent
diagnostic kits from Randox, UK.
Phytochemical Screening
Ethanolic
leaf extract of M. viridis was utilized to carry out the phytochemical screening. Standard procedures were followed to test the phytochemicals such
as alkaloids, carbohydrates, flavonoids, resins, saponins, steroids, tannins,
and phenols (24–27).
Alkaloids
In
a beaker, plant extract of M. viridis (2 mg), distilled water (5 mL), and 1% hydrochloric
acid (8 mL) were taken and stirred carefully and very gently until a reaction happened.
In 2 mL of this mixture, Dragendorff’s reagent (1 mL) was put on dropwise. The
appearance of turbidity or precipitate designates the existence of alkaloids.
Carbohydrates
10 mL of distilled water mixed with 2 mg of plant extract was
filtered, and the filtrate was condensed afterwards. Newly prepared 20% α-naphthol
(2 drops) was added into this filtrate, and then 2 mL of concentrated sulphuric
acid was added dropwise. The formation of a red violet ring indicates the presence
of carbohydrates, which fades away from the surplus inclusion of alkali.
Flavonoids
Plant
extract (2 mg) was dissolved in ethanol (5 mL) and filtered in a small beaker.
Concentrated hydrochloric acid (a few drops) was added carefully to this
filtrate. Then, a small piece of magnesium was incorporated, and the pink or
reddish coloration proved the presence of flavonoids.
Resins
Plant
extract (1 mL) was mixed with copper acetate. The solution was shaken
vigorously and left for a few minutes to separate. A green color appearance in
the solution demonstrated the presence of resins.
Saponins
Plant
extract (0.5 mg) was dissolved in 10 mL of distilled water. Then, the solution
was shaken, covered, and left for 30 min. The solution formed a honeycomb-like
foam that denoted the appearance of saponins.
Steroids
A
0.2 mg of dry extract was shaken with 2 mL of chloroform, and then concentrated
sulphuric acid was added to this mixture carefully by the sides of the test
tube. The appearance of a reddish-brown color at the interphase revealed the
presence of steroids.
Tannins
10
mL distilled water was mixed with 1–2 mg of plant extract and filtered. A few
drops of 0.1% FeCl3 solution were added gently to this filtrate. The
presence of tannins was confirmed by the green, blue-green, or blue-black precipitate.
Phenols
Plant
extract (0.2 mg) was dissolved in a 5% FeCl3 solution. The formation
of green precipitate specified the presence of phenols.
Terpenoids
Plant
extract (0.5 mg) was added in 2 mL chloroform, and then the solution was mixed
with 3 mL concentrated sulphuric acid. The appearance of a reddish-brown color
confirmed the presence of terpenoids.
Statistical Analysis
The
statistical analysis was carried out by one-way analysis of variance (ANOVA),
followed by Dunnett’s post-hoc test or students paired or unpaired T-test where
applicable. The results were represented as mean ± SEM (standard error of the
mean). Results were set as significant when p<0.05.
Results
Effect on Blood Glucose
Level
After diabetes induction, group
III to group VII rats were treated with the ethanolic extract of leaf and whole
plant of M. viridis and a combination
of metformin and plant extract (leaf and whole plant) for two weeks. The
effects of handling extracts and combination therapy for two weeks on blood
glucose levels in alloxan-induced diabetic rats were represented in Figure 1. As can be seen, the BGL (blood glucose level) was decreased
significantly (62.82%) (p<0.05) with
leaf extract (500 mg/kgBW), and (72.89%) (p<0.05)
for the combination of whole plant and metformin (250 and 425 mg/70kgBW), rather than single whole plant extract (43.76%), and combination therapy
of metformin with leaf extract (45.88%) compared to untreated DC rats (Group
II) (31.80 mmol/L). On the other hand, singly metformin (850 mg/70 kgBW)
decreased BGL (65.11%), which was notable (p<0.05)
in contrast to the untreated DC rats. The leaf extract decreased blood glucose
levels from 31.8 mmol/L to 4.9 mmol/L, which was very significant (p<0.05).
Figure 1. Glucose level of blood in diabetic rats after two weeks oral administration of M. viridis extract, metformin, and combination therapy. All experiments were done in triplicate. Data is presented as mean ± SEM; n = 5 for each group. *p<0.05 contrasted to untreated diabetic control rats. †p<0.05 contrasted to normal rats.
Figure 2. Total cholesterol (A), TG levels (B), HDL-C levels (C), and LDL-C levels (D) in diabetic rats after two weeks oral administration of M. viridis extract, metformin, and mixture of metformin and extracts. All experiments were done in triplicate. Data is presented as mean ± SEM; n = 5 for each group. *p<0.05 contrasted to untreated diabetic control rats. †p<0.05 contrasted to normal rats.
In the other treatment, combining whole plant extract with metformin decreased BGL from 24.6 mmol/L to 3.4 mmol/L compared to the untreated DC group, which was also significant (p<0.05). Notably, all the treatments, leaf extract, whole plant extracts, single metformin, and both the combination therapies reduced the blood glucose level remarkably (p<0.05) in treated diabetic groups (III-VII) as opposed to group II (untreated DC group) (see Figure 1). Here, one combination therapy of metformin with whole plant extract showed the maximum reduction in BGL, which was 72.89%.
Effect on Lipid Profiles
Several studies reported
that diabetes caused by alloxan surged the blood glucose levels effectively in
animal models. Together, they can raise TC, TG, and LDL-C cholesterol levels and
decline HDL-C levels sequentially (28-30).
It can be seen from Figure 2 that, in DC rats with no treatment (group II), all
the lipid profiles, for instance, TC, TG, and LDL-C increased when compared
to NC rats (group I). On the contrary, HDL-cholesterol decreased in the untreated
DC group compared to the NC group. These findings agree with the previously
reported work: alloxan induction aggressively deteriorates the lipid profiles
in untreated DC rats, in addition to blood glucose level increments (22, 23). After two weeks of treatment with the leaf extract,
plant extract, and blending therapy of metformin with the leaf, the plant
extract reduced the elevated levels of TC, TG, and LDL-C. They increased the
low levels of HDL-C in respective diabetic rats (group III – group VII), as
seen in Figure 2. It has been noticed that the TC level (29.17%), TG level
(89.55%) (p<0.05), LDL-C
level (68.67%) (p<0.05) increased,
and HDL-cholesterol level (25.52%) decreased in alloxan-induced untreated diabetic
rats as contrasted with their corresponding normal rats after diabetes
induction.
Interestingly, it was observed
that a noticeable drop in TG, LDL-C (p<0.05) and surge in HDL-C levels (p<0.05) in alloxan-induced diabetic
rats handled with ethanolic leaf extract of M.
viridis, metformin alone, and metformin with whole plant extract after two
weeks treatment. In contrast, whole plant extracts and one
combination of metformin with leaf extract improved the dyslipidemic condition,
particularly TG, LDL-C, and HDL-C in treated diabetic rats. However, it did not
seem very satisfactory. On the other hand, no therapy showed a noteworthy
response in reducing TC in treated hyperglycemic rats except the whole plant
extract. Therefore, the conclusion drawn here is that both the leaf extract
and one blending therapy of metformin with the entire plant extract produced beneficial
effects on TG, LDL-C, and HDL-C levels in diabetic rats following two weeks of treatment.
Phytochemical constituents
Result
Alkaloids
+
Carbohydrates
-
Resins
+
Terpenoids
+
Tannins
+
Saponins
-
Flavonoids
+
Phenols
+
Steroids
+
Preliminary Phytochemical Screening
Phytochemicals
estimations were carried out for qualitative analysis to reveal the existence
or lack of major secondary metabolites such as alkaloids, carbohydrates, phenolic
contents, terpenoids, saponins, resins, steroids, etc., in the extracts of the
leaf of M. viridis. The
results of phytochemical screening are summed up in Table 1. Alkaloids, resins,
tannins, steroids, terpenoids, flavonoids, and phenolic compounds appeared in the
plant extract. However, saponins and carbohydrates were absent in the extract.
Discussion
The
primary focus of selecting the M. viridis
medicinal plant and applying it as a therapy in diabetic rats was to see any
beneficial outcome in the ethanolic extract in managing chemically induced
diabetes mellitus. However, this helpful result would come either by reducing
elevated blood glucose levels or correcting any lipid profile disturbance. To
induce diabetes in experimental animals, a single intraperitoneal injection of
alloxan (2,4,5,6-tetraoxypyrimidine) was utilized at a dose of (120 mg/kgBW). The
mechanism of how alloxan induces diabetes in experimental animals and,
consequently, its deteriorated effect is reasonably well understood. Following the
previously reported study, two rationales might be accountable. One is the particular
retardation of glucokinase, a glucose sensor of the beta cell resulting in
insulin secretion inhibition in response to glucose. Second is the capability
of alloxan to prompt reactive oxygen species (ROS) formation, which in
succession causes the selective death of beta cells (22).
Noteworthy, chemically, alloxan is a diabetogenic agent that is inactive but
converted to an active toxin inside the body called protoxin. This foreign
substance is subjected to intracellular metabolism, generating ROS in redox
cycling reactions between alloxan and dialuric acid (22).
It has been observed in this study that only one dose of alloxan injection
caused the BGL increment significantly in untreated DC rats & diabetic rats
(group III-VII) as compared to the NC group (with no alloxan treatment) as can
be seen from Figure 1. The significant increase in BGL in animals
might be caused by the selective uptake of alloxan to beta cells via glucose
transporter, GLUT2, followed by several factors such as origination of ROS,
gradual deterioration of beta cell function, beta cell demise by necrosis, and
finally diabetes mellitus which is insulin dependent.
All
these phenomena produced chemical diabetes termed alloxan diabetes (22).
After daily treatment for two weeks with the leaf and plant extract of M. viridis singly, combining these
extracts with metformin reduced the elevated BGL significantly (p<0.05), as found in
Figure 1. Among the treatments, leaf extract (500 mg/kgBW) (62.82%) and the
amalgamation of whole plant and metformin (250 and 425 mg/70kgBW)
(72.89%) decreased BGL more effectually. Single oral administration of
metformin reduced BGL (65.11%) significantly compared to the untreated DC
group. Similar observations were found in previously reported studies where
combination therapy worked more effectively in managing hyperglycemia than a
single therapy (29–33). This result suggests
that the leaf of M. viridis and the
combination of whole plant extract with an oral antidiabetic agent, metformin,
can control hyperglycemia by stimulating or regenerating the beta cells to
secrete insulin from islets of Langerhans.
On
the contrary, the mode of action of the reference drug, metformin, on lowering
BGL is explicit (34, 35). Here, the observed
significant antihyperglycemic effect of leaf extract might be due to
phytochemicals such as flavonoids, terpenoids, phenols and tannins. The most
significant synergistic effect in lowering blood sugar levels was observed with
the combination of whole plant extract and metformin. According to the literature,
phytochemicals such as flavonoids (36, 37), tannins (38),
and terpenoids (39, 40) present in different
plant extracts were found in the management of diabetes (41).
In
insulin-dependent type 1 diabetes with poor glycemic control, lipid
abnormalities such as increased plasma triglycerides, LDL-C, and low levels of
HDL-C are often noticed (42, 43). Insulin deficiency,
insulin resistance, and hyperglycemia could change plasma lipid/lipoprotein
metabolism, resulting in lipoprotein abnormalities (44, 45). This study also
investigated TG, TC, LDL-C, and HDL-C lipid profiles. Compared to the NC group
in the untreated DC group and diabetic (II-VII) groups, all the parameters, for
instance, TC, TG, and LDC-C levels were climbed, whereas HDL-C declined notably.
Similar observations were found in previously reported studies (29-31, 46). Diabetic rats treated
with either M. viridis extract (leaf
and whole plant) or one combination therapy of extract with reference
antidiabetic drug, metformin (leaf with metformin) for two weeks exhibited a
remarkable drop in TG and LDL-C levels and a notable rise in HDL-C level when
compared with untreated DC group. No noticeable response was found in reducing
the serum TC level in hyperglycemic rats following two weeks of treatment with leaf
extract and combination therapy.
Only
whole plant extract provided a significant outcome in reducing the TC level, as
can be seen in Figure 2A. This result of correcting dyslipidemia agrees well
with previous studies in animal models with diabetes (41).
The findings here suggested that ethanolic crude extract of M. viridis may restore the beta cells
and thus potentiate insulin release in pancreatic islets of alloxan-induced
diabetic rats. In a previously reported study, a water-soluble alcoholic
extract of Gymnema sylvestre possessed
antidiabetic features, including better management of blood glucose level, betterment
in hyperlipidemia, enhancement in beta cell functions, and beta cell retrieval
in animal diabetic models (47).
Several studies reported that phytochemicals found in medicinal plants have
multiple beneficial effects in fighting diabetes mellitus and associated
complications. For example, flavonoids, terpenoids, and phenolic acids have antidiabetic
potentialities (48).
Flavonoids could revive the defective beta cells in chemically induced
hyperglycemic rats (49).
Phenolics could act as effective antihyperglycemic agents in animal diabetic
models (50).
The phytochemical screening of the ethanolic extract of M. viridis showed that it contains abundant terpenoids, flavonoids,
phenols, steroids, and alkaloids. Several studies have demonstrated that the
phytoconstituents from different plant extracts, for instance, phenolic compounds, flavonoids, terpenoids, alkaloids, tannins,
saponins, glycosides, glycolipids, etc., have been found to have strong
antidiabetic effects (51). The equeous extract of Piper longum root showed significant
antihyperglycemic activity due to the presence of phytoconstituents such as
alkaloids and glycosides (52).
The antidiabetic effect was also found in Hibiscus sabdariffa extract, and the authors suggested that
phytoconstituents such as flavonoids, triterpenes, tannins, and phenols
possessed the potential to reduce blood glucose levels (41). Phytochemicals
such as tannins, flavonoids, terpenoids, phenolic compounds, etc., from the
leaf of Discopodium penninervum Hoechst,
were found to be effective against antihyperglycemic
and antihyperlipidemic effects (37).
Therefore,
phytochemicals present in ethanolic extract of M. viridis might provide practical antihyperglycemic and antihyperlipidemic
effects in treated diabetic rats by several mechanisms, such as boosting up the
insulin secretion by energizing the beta cells of islets of Langerhans or
marked transport of glucose to peripheral tissue and regenerating the damaged beta
cells as mentioned earlier (53).
It was evident from the data that treatment with leaf and a combination of
metformin with whole plant extract significantly improved the lipid
abnormalities. The obvious lipid lowering consequence might be due to declined fatty
acid and cholesterol synthesis in treated diabetic animals with plant extracts (53).
Diabetes and its associated complications can be more effectively managed if
the TC and TG levels are sufficiently low (54).
On the contrary, the lipid-lowering effect of metformin was due to rectifying
abnormal glucose metabolism and/or lowering the hepatic production of very low-density
lipoprotein (55).
In this study, metformin provided a significant improvement in normalizing the
dyslipidemia and betterment the glycemic control in diabetic rats (Group V).
Since the amalgamation of extract with metformin made additional augmentation
in lowering BGL and in healing the lipid profiles excluding the TC that
produced by metformin or extract alone, it might be advised that M. viridis might potentiate the
hypoglycemic and hypolipidemic effect of metformin. The factual mode of action
of antihyperglycemic and antihyperlipidemic outcome of M. viridis extract remains unclear and more investigations are
necessary to unfold this observation.
Conclusion
The
preliminary investigations suggest that M.
viridis had the potential to diminish the elevated blood glucose singly and
had synergistic results in lowering hyperglycemia with metformin. M. viridis extracts and amalgamation of
metformin with extracts significantly mitigated the abnormalities in lipid
profiles in alloxan-induced diabetic rats as opposed to untreated DC rats. These
pharmacological effects could be ascribed to the existence of phytochemicals
such as flavonoids, terpenoids, phenolic constituents, resins, tannins,
steroids, etc. This investigation suggests that M. viridis could be a safe and valuable mono or adjuvant treatment
with a reference oral hypoglycemic agent to achieve glycemic control and more
effective antihyperlipidemic action. The dynamic pharmacological actions found
in M. viridis extract could be combined
wisely for maximum therapeutic action with minimum adverse effects. However,
more investigations are essential to reveal the mechanism behind the
antihyperglycemic and antihyperlipidemic effects.
This research was designed to examine the phytochemicals of Mentha viridis (M. viridis) ethanolic extract and the antidiabetic and antihyperlipidemic activities in alloxan-induced animal models. Diabetes was induced chemically by administering a unit dose of alloxan at 120 mg/kg BW. After alloxan induction, hyperglycemic rats were dealt with ethanolic extract of leaf and whole plant, metformin, and a mixture of leaf extract with metformin and whole plant extract with metformin for two weeks. Ethanolic extract of leaf and whole plant, metformin, and a combination of both leaf and whole plant extract with metformin therapies reduced glucose levels in the blood compared with the diabetic negative control group after two weeks of treatment. However, among the therapies, the ethanolic leaf extract and the combination of whole plant extracts with metformin were found to be the most effective (p<0.05), with reductions of 62.82% and 72.89%, respectively. After diabetes induction, the serum level of TG (triglycerides), TC (total cholesterol), LDL-C (low-density lipoprotein-cholesterol) escalated notably (p<0.05), and HDL-C (high-density lipoprotein-cholesterol) level decreased remarkably (p<0.05) in hyperglycemic rats as opposed to healthy normal rats. Ethanolic leaf extract and a combination of whole plant extract with metformin significantly minimized the elevated extent of TG and LDL-C. They surged HDL-C, but the TC level was reduced by whole plant extract only after two weeks of treatment. The standard procedures were used to identify the phytochemical compounds of the medicinal plant M. viridis. The phytochemical compounds such as alkaloids, resins, tannins, phenols, flavonoids, steroids, and terpenoids appeared in the ethanolic leaf extract of M. viridis. The findings suggest that M. viridis might provide better glycemic control and hypolipidemic effect in diabetic rats when administered alone or combined with oral antidiabetic agents. Incorporating M. viridis extract with metformin in improving hyperglycemic and hyperlipidemic conditions in diabetic rats proves that M. viridis has a synergistic effect, which could enhance the antidiabetic activity of oral hypoglycemic agents.
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