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Medicinal Plants for the Treatment of Type 2 Diabetes
Camellia species
Camellia Joponica
Camellia japonica is known as a garden plant whose flowers and seeds have been used for traditional
cosmetics in East Asia (Ochiai et al., 2018). Uddin et al. evaluated EtOAc-soluble fruit peel extract
from C. japonica (Theaceae) for PTP1B inhibition in vitro. Four new oleanane-type triterpenes were
identified, together with six known components of this class and many of them showed significant effect on PTP1B inhibition with IC
2014). In another obese mouse model, rats fed with 1% C. japonica seed extract for 53 days showed
increased fecal fat excretion as well as a reduction of body weight gain and lipid parameters in the liver
and in plasma. Furthermore, they observed a delay of lipid-induced hypertriglyceridemia after a single
consumption of C. japonica (Ochiai et al., 2018). A study with hypercholesterolemic rat model showed
that C. japonica fruit extracts have a strong cholesterol-lowering effect caused by a reduction of triglyc-
eride, low-density lipoprotein and serum total cholesterol, as well as an increase in serum high-density
lipoprotein. In addition, C. japonica fruit extracts decreased lipid peroxidation in plasma by inhibiting
the production of thiobarbituric acid reactive substance (TBARS) (Lee et al., 2016). C. japonica may
be a potent therapeutic option for the improvement of many diseases related to hypercholesterolemia,
however, more investigations need to be performed to determine a clear mechanism of action for C.
japonica in the treatment of T2D.
values in the range of 3.77 ± 0.11 to 6.40 ± 0.81 µM (Uddin et al.,
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Camellia sinesis L.O. Kuntze (Green tea)
Deng et al. (2018) showed the ameliorated therapeutic potency of bioactive compounds extracted from
green tea in the high fat diet/streptozocin-induced diabetic mice. After oral administration of tea peptides
(1000 mg/kg, bw/day) for 5 weeks, rats significantly decreased FSG level, and the amount of creatinine,
total urinary protein, and urine nitrogen related to the impairment of glomerular filtration function.
The mechanism based on stimulation of the polyol PKCζ/JNK/NF-κB/TNF-α/iNOS and AGEs/RAGE/
TGF-β1 pathways, upregulation of podocin expression in the glomeruli as well as decrease in release of
pro-inflammatory cytokines (Deng et al., 2018). Hua et al. (2018) evaluated the effects on enzymatic
inhibition of the novel acylated flavonol tetraglycoside (camellikaempferoside C, 1), flavone glycosides
(FGs), other flavone and flavone glycosides (FGs) identified from C. sinensis. The kaempferol monoglycoside inhibited intestinal glucosidase activity with IC
diglycoside displayed inhibitory activity against α-amylase with IC
suggested the interaction of kaempferol monoglycoside with α-glucosidase and kaempferol diglycoside
with α-amylase via hydrogen bonding and van der Waals forces led to the quench of intrinsic fluorescence of both enzymes (Hua et al., 2018). A clinical trial of 120 overweight women showed that green
tea in the absence of metformin decreased FSG level and enhanced glycaemic control and lipid profile
including total cholesterol and LDL-cholesterol. These results suggested that green tea extract could
be a promising alternative for reducing risk of T2D in overweight women (Alves Ferreira et al., 2017).
Ludwigia octovalvis (Jacq.) P.H. Raven
Ludwigia octovalvis (Onagraceae) has traditionally been used as a supplemental therapy for the
treatment of many diseases such as edema, nephritis, hypotension and diabetes (Lin et al., 2017). The
phytochemicals of the herb of L. octovalvis contain beta-sitosterol, oleanolic acid, gallic acid, ellagic acid,
value of 40.02 ± 4.61 μM, while kaempferol
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at 0.09 ± 0.02 μM. Molecular docking
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Medicinal Plants for the Treatment of Type 2 Diabetes
quercetin, luteolin, apigenin, tormentic acid, 2-alpha-hydroxy ursolic acid, daucosterol, maltol, methyl
brevifolincarboxylate and 3, 4, 8, 9, 10-pentahydroxydibenzo[b, d]pyran-6-one (Yan & Yang, 2005).
Morales et al. measured the inhibitory effect on new pancreatic lipase and α-glucosidase of L. octovalvis
hydroalcoholic extract in comparison with orlistat, acarbose, and a C. sinensis hydroalcoholic extract. L.
octovalvis hydroalcoholic extract and its ethyl acetate fraction inhibited α-glucosidases with IC
values
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of 700 and 250 μg/mL, lipase with 480 and 718 μg/mL, whereas C. sinensis displayed enzymatic inhibi-
tion at IC
competitive inhibition of α-glucosidases (IC
the most active compound in the uncompetitive lipase inhibitors (IC
values of 260 and 587 μg/mL, respectively. Gallic acid, ethyl gallate showed the highest and
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832 μM and 969 μM, respectively), while isoorientin was
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201 μM) (Morales et al., 2018).
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Lin et al. published a study on L. octovalvis extract (LOE) in differentiated C2C12 muscle cells, HepG2
hepatocellular cells, STZ-induced diabetic mice and HFD-induced diabetic mice, which reported an
obvious reduction in the hyperglycemia of this extract. LOE and its bioactive compound (β-sitosterol)
stimulated significantly the phosphorylation of AMPK in C2C12 muscle and HepG2 hepatocellular
cells. In STZ-induced diabetic mice, both LOE and β-sitosterol showed an anti-hyperglycemic potential
when compared to metformin, an antidiabetic standard drug. Furthermore, mice fed a HFD enhanced
glycemic control and memory presentation after the treatment of LOE (Lin et al., 2017).
Andrographis paniculata Nees
Andrographis paniculata known as a valuable natural product is widely used in traditional medicine for
improvement of hepatic and cardiovascular function as well as treatment of diarrhea, fever, respiratory
illness and as an antioxidant. The phytochemicals of A. paniculata revealed that it may contain over 55
ent-labdane diterpenoids, 30 flavonoids, 8 quinic acids, 5 rare noriridoids and 4 xanthones (Hossain
et al., 2014). Andrographolide is the major active component derived from this medicinal herb. An in
vivo study showed the improvement of Andrographolide on streptozotocin (STZ)-induced diabetic reti-
nopathy in mice. The results suggested that this compound prevented the expansion of retinal vessels
in STZ-induced proliferative diabetic retinopathy mice, which was exhibited by immunofluorescence
staining for cluster of differentiation. In STZ-induced non-proliferative diabetic retinopathy mice, Evans
blue permeation results showed the reduction in blood-retinal barrier malfunction by the treatment of
Andrographolide. Moreover, Andrographolide also reduced the increase in vascular endothelial growth
factor (VEGF) and vitreous cavity, retinal mRNA expression of VEGF and serpine1, IL-1β, IL-6, TNF-α
and tissue factors (Yu et al., 2015). Li has synthesized a new andrographolide derivative AL-1 by the
conjugation of andrographolide and lipoic acid, then indicated the influence of AL-1 on insulin resistance
in a high-fat diet/streptozocin-induced diabetic rats as well as unclear mechanism related to its action
(Li et al., 2015). These results showed a significant hypoglycaemic potential of AL-1 (40 and 80 mg/
kg). It also increased HDL level and insulin sensitivity, concurrently, reduced cholesterol level and the
homeostasis model assessment of insulin resistance. Furthermore, AL-1 restored mass and function of
pancreatic tissues, inhibited phosphorylation of p65 and IκBα in RIN-m cells caused by high glucose
state (Li et al., 2015). Deoxyandrographolide (DeoAn), another bioactive constituent extracted from the
A. paniculata also exhibited the effects on use of glucose for muscle movement and blood glucose levels.
A dose-dependent administration of this compound had the ability to ameliorate glucose transporter 4
(GLUT4) translocation, leading to glucose uptake with no change in the total content of GLUT4 and
GLUT1 in L6 myotubes. It also stimulated PI-3-K- and AMPK-dependent signaling pathways followed
by increasing in glucose transportation. Additionally, STZ-induced diabetic rats treated with DeoAn
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Medicinal Plants for the Treatment of Type 2 Diabetes
exhibited lower postprandial blood glucose levels concurrently, the repression of increase in seum insulin, FSG, triglycerides and LDL- cholesterols was found in db/db mice (Arha et al., 2015). Akhtar et
al. indicated that A. paniculata plant extract also had anti-diabetic capacity for obese and obese mice
models. When compared with normal groups, the amount of allantoin, creatinine and lactate increased
significantly in the urine of obese groups, while the high concentrations of glucose, taurine and choline as well as the decrease of lactate, acetate, formate, succinate, acetoacetate, citrate, 2-oxoglutarate,
dimethylamine, creatinine, hippurate and allantoin levels were observed in obese-diabetic rats. A. pa-
niculata leaf aqueous extract improved the disturbed metabolic functions of obese-diabetic rats close to
physiological conditions (Akhtar et al., 2016). Of note, treatment with A. paniculata leaf extract (50,
100 and 200 mg/kg/day), or with pure Andro (15, 30 and 60 mg/kg/day) also reduced cognitive decline
and oxidative stress, induced acetylcholinesterase inhibition, ameliorated hyperglycemic state and lack
of insulin in diabetic rats (Thakur et al., 2016).
Trigonella foenum-graecum L.
Trigonella foenum-graecum (Methika in Sanskrit) has been used in India folk medicine as a kaphahara
(balancing kapha) herb for indicating in Prameha or early diabetes mellitus and reducing lipid levels of
blood. The LC–MS/MS analyses showed various bioactive compounds isolated from Trigonella like
apigenin, quercetin, kaempferol, calycosin, pratensin, orientin, tricin, luteolin and gallic acid (Banerjee
et al., 2019). In a streptozotocin-induced diabetic rat model, Trigonella foenum-graecum remarkablely
decreased the FSG back towards normal levels. It showed antioxidant property to defend the organs
like liver and pancreas by reducing of TBARS levels and enhancing antioxidant activities (Sankar et
al., 2012). According to another study, Trigonella foenum-graecum also displayed anti-hyperglycemic
effect and ameliorated the levels of hydrogen peroxide, malondialdehyde and 4-hydroxynonanal, the
activities of catalase, superoxide dismutase and glutathione peroxidase as well as transcription of thgenes
of these enzymes in liver and brain tissues of diabetic mice (Sharma et al., 2015). In a clinical trial, T.
foenum-graecum seed powder solution showed several therapeutic benefit on lipid metabolism in newly
diagnosed T2D patients, including decreased levels of triglycerides, total cholesterol and LDL- cholesterol, concurrently, increased HDL-cholesterol level. Hence, T. foenum-graecum may contribute new
effective alternatives for the symptomatic improvement in T2D patients (Geberemeskel et al., 2019).
Tinospora cordifolia
Tinospora cordifolia has been widely used as an herbal source for the treatment of several human ailments, including diabetes mellitus (Rajalakshmi & Anita, 2016). The chemical components of Tinospora
cordifolia included different groups such as phenolics, alkaloids, steroids, glycosides, polysaccharides,
aliphatic compounds and the higher levels of protein, phosphorus and calcium were found in leaves.
Spectroscopic studies established the structure of clerodane furono diterpene glucoside (amritoside A,
B, C, and D) in stem (P. Sharma et al., 2019). Both in vitro and in vivo analysis showed that sedimental
extract of Tinospora cordifolia presented antioxidant capacity of around 2046 times and as a potential
drug to ameliorate many signals of tissue damages in chronic diseases like diabetes (Kannadhasan &
Venkataraman, 2013). Agrawal et al. investigated the therapeutic potential of Tinospora cordifolia in
diabetic retinopathy in STZ-induced rats, particularly its antihyperglycemic, angiogenic, antioxidant and
anti-inflammatory properties. The results indicated decrease in blood glucose and glycated hemoglobin
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Medicinal Plants for the Treatment of Type 2 Diabetes
in mice for 24 weeks after use of Tinospora cordifolia extract (250 mg/kg). It also prevented cataract
development, reduction of glutathione and catalase and thickening of basement membrane of the retinal
and glomerular vasculature of diabetic rat. Treatment with Tinospora cordifolia decreased destruction
of pancreatic islet structure, angiogenic markers and anti-inflammatory factors TNF-α and IL-1β, which
are different biomarkers of diabetic retinopathy (Agrawal et al., 2012). Furthermore, the hydrophilic
extract of Tinospora cordifolia stem (TCSE) increased insulin secretion and cell viability in rat insuli-
noma (RIN)-m5F cells as well as the glucose uptake and GLUT4 translocation in 3 T3-L1 adipocytes via
PI3K pathway. Rats administered TCSE presented reduction of total cholesterol, triglyceride, dipeptidyl
peptidase-4, and TBARS, concurrently, increase in hepatic glycogen and insulin levels as well as glucose
transporter 4 protein expression in adipose tissue and liver (Sharma et al., 2019). Another study reported
that a novel polysaccharide extracted from Tinospora cordifolia methanolic extract significantly reduced
plasma glucose, HbA1c, total cholesterol, triglycerides, and increased HDL cholesterol, hemoglobin
and tissue glycogen. In addition, this compound had the ability to restore insulin, the altered enzymes
associated with carbohydrate metabolism, C-peptide, (14) C-glucose oxidation levels and regenerate
β-cells in pancreatic islets (Rajalakshmi & Anita, 2016).
Fagonia cretica
The active compounds isolated from a crude extract of Fagonia cretica included stigmasterol, quinovic
acid, quinovic acid-3β-O-β-D-glucopyranosyl-(28®1)-β-D-glucopyranosyl ester and quinovic acid-3βO-β-D-glycopyranoside, both of them presented effects on DDP-4 inhibition with IC
values of 30.7,
50
57.9, 23.5 and >100 µM, respectively (Saleem et al., 2014). The presence of some phenolic glycosides,
such as quercetin-3-O-rutinoside, kaempferol-3(6’-malonylglucoside, kaempferol-3-O-glycoside,
kaempferol-3-O-rutinoside, isorhamnetin-3-O-rutinoside, and isorhamnetin 3-(6’’-malonylglucoside)
in Fagonia cretica were reported. Nazir et al showed the α-glucosidase inhibition of Fagonia cretica,
leading to decrease plasma glucose level and the prevention pancreatic islet cells from damages caused
by streptozotocin or nictotinamide treatment (Nazir et al., 2017). Furthermore, Fagonia cretica extracts
also induced production of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide
1, enhanced cellular hormone content, and upregulated gene expression of GIP, prohormone convertase
and proglucagon (Jafri et al., 2016).
Ficus bengalensis
Traditional medicines have considered Ficus bengalensis as benefical, economical and safe ethnomedicines
for several human ailments. The therapeutic potential of Ficus bengalensis roots and barks was reported
for the treatment of T2D due to decrease in FSG level in diabetic rats (Singh et al., 2009). In an animal
hypercholesterolaemic model, rabbits treated with Ficus bengalensis aqueous bark extract showed the
low levels of triacylglycerol, cholesterol, LDL, VLDL-cholesterol and reduction of lipid peroxidation.
This extract also activated various antioxidant enzymes including catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase (Shukla et al., 2004). Moreover, Ficus bengalensis had
the ability to restore amount of serum glycolytic, electrolytes enzymes and hepatic cytochrome P450
dependent enzyme systems and decrease the production of liver and kidney lipid peroxides in diabetic
rats. However, detailed studies are established to further investigate the therapeutic effects of Ficus
bengalensis on diabetes mellitus (Gayathri & Kannabiran, 2008).
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Medicinal Plants for the Treatment of Type 2 Diabetes
CONCLUSION
In conclusion, biological active compounds of plants and natural extracts acting through different
mechanisms are effective therapeutic alternatives for the prevention of T2D development. Since studies with several of these medicinal plants are explorative and desultory, it is necessary to investigate
comprehensively and find new potential candidates for future use.
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