Biomedicine & Pharmacotherapy 142 (2021) 112109

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Biomedicine & Pharmacotherapy

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

Health promoting benefits of pongamol: An overview

Shamima Jahan a, Md. Hasan Mahmud a, Zidan Khan a, Ashraful Alam a, Anees Ahmed Khalil b,
Abdur Rauf c, *, Abu Montakim Tareq a, Firzan Nainu d, Syed Mohammed Tareq a, Talha
Bin Emran e, *, 1, Muneeb Khan f, Ishaq N. Khan g, Polrat Wilairatana h, *,
Mohammad S. Mubarak i, *
a
Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh
b
University Institute of Diet and Nutritional Sciences, Faculty of Allied Health Sciences, The University of Lahore, Pakistan
c
Department of Chemistry, University of Swabi, Swabi, Anbar 23430, Khyber Pakhtunkhwa, Pakistan
d
Faculty of Pharmacy, Hasanuddin University, Tamalanrea, Makassar 90245, Indonesia
e
Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh
f
Department of Human Nutrition and Dietetics, Riphah College of Rehabilitation and Allied Health Sciences, Riphah International University Lahore, Pakistan
g
Institute of Basic Medical Sciences, Khyber Medical University, Peshawar 25100, Pakistan
h
Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
i
Department of Chemistry, The University of Jordan, Amman 11942, Jordan

A R T I C L E I N F O A B S T R A C T

Keywords: Plant-derived chemicals are a source of novel chemotherapeutic agents. Throughout the human civilization,
Pongamol these novel chemicals have led to the discovery of new pharmacological active agents. Research on herbal
Health benefits medicine is of great importance, as most of the active agents used for treating numerous diseases are from natural
Anticancer
sources, while other agents are either semisynthetic or synthetic. Pongamol, a flavonoid, which is the main
Antioxidant
Antimicrobial
constituent of Pongamia pinnata, is one such active agents, which exhibits diverse pharmacological activities.
Anti-diabetic Various in vivo and in vitro studies revealed that pongamol is a potentially active agent, as it exerts anticancer,
Mechanisms of action anti-inflammatory, antioxidant, antimicrobial, and anti-diabetic activities. Accordingly, the aim of the present
review was to give an up-to-date overview on the chemistry, isolation, bioavailability, pharmacological activity,
and health benefits of pongamol. This review focuses on the medicinal and health promoting activities of pon­
gamol, along with possible mechanisms of action. For this purpose, this review summarizes the most recent
literature pertaining to pongamol as a therapeutic agent against several diseases. In addition, the review covers
information related to the toxicological assessment and safety of this phytochemical, and highlights the me­
dicinal and folk values of this compound against various diseases and ailments.

1. Introduction progression [3]. The gene for cyclin-dependent kinase 2 (CDK2) is linked
with regulation of the normal cell cycle. In most cancer cases, the gene
Cancer continues to be a global concern, despite the advent of deviates from its normal activity indicated by overexpression, thus
technological and pharmaceutical improvements over the past a few causing cancer [3,4]. The initial stage of cancer is the formation of
decades [1]. Cancer is the abnormal division and proliferation of cells tumor cells, which proliferate further to form a cancer cell line. Methods
that stems from a myriad of factors [2,3]. Cancer cells arise when the of cancer treatment include surgery, radiotherapy, and anti-cancer
normal tissue of the body is unable to maintain the signals that regulate drugs (chemotherapy) among others. There are two types of tumor:
normal cell division. In this respect, genes are associated with cancer benign (not cancerous) and malignant [3,5]. A benign tumor is compact

* Corresponding authors.
E-mail addresses: shamimaj058@gmail.com (S. Jahan), mdhasanmahmud6312@gmail.com (Md.H. Mahmud), zidankhan9090@gmail.com (Z. Khan),
tusherashrafulalam@gmail.com (A. Alam), aneesahmedkhalil@gmail.com (A.A. Khalil), mashaljcs@yahoo.com (A. Rauf), montakim0.abu@gmail.com
(A.M. Tareq), firzannainu@unhas.ac.id (F. Nainu), mail2babor@gmail.com (S.M. Tareq), talhabmb@bgctub.ac.bd (T.B. Emran), muneebkhan2001@gmail.com
(M. Khan), ishaqkhan.ibms@kmu.edu.pk (I.N. Khan), polrat.wil@mahidol.ac.th (P. Wilairatana), mmubarak@ju.edu.jo (M.S. Mubarak).
1
https://orcid.org/0000-0003-3188-2272.

https://doi.org/10.1016/j.biopha.2021.112109
Received 1 July 2021; Received in revised form 22 August 2021; Accepted 23 August 2021
Available online 27 August 2021
0753-3322/© 2021 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
S. Jahan et al. Biomedicine & Pharmacotherapy 142 (2021) 112109

in one place and is incapable of spreading. Such tumors can be removed showed that people with cancer, for example, often turn to alternative
by surgery. On the other hand, a malignant tumor is highly detrimental treatments, especially medicinal plants, as a potential cure. Published
as compared to a benign tumor, and has the capability for metastasis, work showed that approximately 3000 plants with anti-cancer charac­
meaning they can spread from one site to another, thus forming teristics are recognized worldwide [24]. In addition, researchers indi­
cancerous cells in other parts of the body. While benign cells can be cated that over 30% of patients diagnosed with cancer in metropolitan
eliminated by surgery, malignant cells require greater undertaking, and regions of Mexico utilize plant extracts as an alternative or supple­
are difficult to eliminate. Within this context, most cancers fall into one mentary treatment [25]. These findings highlight the importance of
of three main groups: carcinomas, sarcomas, and leukemias. Among all complementary and alternative medicine in the majority of Mexican
cancer cell developments, carcinomas are the most prominent in communities and cultures [26]. On the other hand, several African
magnitude, comprising about 90% of all cancer cases. In the United traditional plants, namely Aloe ferox, Hypoxis hemerocallidea, Suther­
States, approximately 1,000,000 people have cancer, and half a million landia frutescens, and Leonotis leonurus exhibited anti-diabetic effects
people die from cancer every year, with breast, prostate, lung, and colon [27]. In addition, phytochemical studies indicated that numerous
cancer account for most cancer cases [3,6,7]. plant-derived compounds including tannic acid, flavonoids, tocopherol,
Free radicals are atomic structures with unpaired electrons in their curcumin, ascorbate, carotenoids, and polyphenols exhibit antioxidant
outmost shells, and can be very highly reactive and unstable [8]. Free properties [28]. Moreover, the antibacterial action of plants is attributed
radicals can donate or accept an electron from other stable molecules, to secondary metabolites. Phenolics and polyphenols (flavonoids, qui­
thus rendering them unstable. Reactive oxygen species (ROS) and nones, tannins, and coumarins), terpenoids, alkaloids, lectins, and
reactive nitrogen species (RNS) include moieties such as hydroxyl polypeptides are the major classes of phytochemicals with antimicrobial
radical (⋅OH), superoxide anion (O2¡•), hydrogen peroxide (H2O2), ni­ effects. In this context, herbs are still utilized in traditional medicine to
tric oxide (NO), and peroxynitrite (ONOO− ). These species are respon­ treat a variety of infectious diseases in a number of nations, including
sible for oxidative stress (OS), and can cause damage to healthy tissues Armenia [29].
in the body [9]. Free radicals can arise internally from normal metabolic Pongamol, a flavone derivative, contains hydroxyl, methoxy, and
processes in the body or can result from external effects such as exposure ethylene double bonds [30]. It is present in Pongamia pinnata (karanjin)
to radiation, X-ray, and some chemical compounds [10]. In this respect, seeds, [31] and the roots of Tephrosia purpurea (TP) [32]. This compound
OS refers to the deviation from the normal ratio of free radical pro­ exhibits a wide range of anticancer activity. It inhibits the expression of
duction and antioxidants. This process causes a cascade of reactions, the CYP1A1 gene, thus preventing the growth of breast cancer cells [33].
which lead to intracellular and extracellular damage, and can be asso­ Similarly, research findings indicated that it selectively inhibits
ciated with cancer cell proliferation and diabetes [8,11–13]. prostate-specific antigen (PSA) production [34]. Furthermore, ponga­
Infectious diseases have been associated with humans since the mol decreases acid production and increases mucin production, which
beginning of history. Infections are the major cause of death; in 2009, acts as a protective measure against gastric cancer [35]. In addition,
among the 53 million deaths, one-third died because of various infec­ published research demonstrated that pongamol reduces the amount of
tious diseases. Bacteria, viruses, and parasites can all cause infections. enzymes in the liver and plays a protective role against liver cancer [36].
Within this context, bacteria are classified as gram-positive or gram- Pongamol also inhibits prostate-specific antigen (PSA) production in
negative, and most bacteria selectively infect an organism, which PC-3 prostate cancer cells [34]. Moreover, the compound selectively
means that a particular bacterial species targets only a specific organ in restricts lipid peroxidation, thus playing a role as an antioxidant [37],
the body and not others [14]. and has the capability to inhibit both gram-negative and gram-positive
On the other hand, diabetes is a common, and possibly the world’s bacteria [38]. It also lowers blood glucose levels, [39] and causes
fastest growing, metabolic disease, which is characterized by chronic increased glucose uptake in L6 skeletal muscle [39], which indicates it is
hyperglycemia, caused by impaired insulin secretion, response, or both a potential anti-diabetic agent. Based on the above discussion, the pre­
[15]. In this respect, the Western Pacific region has the highest number sent review focuses on the pharmacological activity of pongamol,
of diabetes patients, which comprise approximately 37.5% of the pop­ highlighting its ability as an active medicinal and chemotherapeutic
ulation [16]. Diabetes mellitus arises from a metabolic disorder, indi­ agent against various conditions, including cancer. In addition, the re­
cated by distorted insulin secretion from the Langerhans cell islets of the view discusses the chemistry, toxicology profiles, and health promoting
pancreas into the blood stream [17]. When insulin production is mini­ aspects of pongamol to ensure its safe administration into humans.
mized, glucose levels in the blood become elevated over time, which
initiates various diseases of malfunction, including kidney and nerve 2. Chemistry of pongamol
damage [18]. There are two types of diabetes: type 1 and type 2. Most
diabetes cases in children and adolescents are of type 1. The cause of Pongamol, 1-(4-methoxy-5-benzofuranyl)-3-phenyl-1,3-propane­
Type 1 diabetes is an autoimmune disease catalyzed by the T dione, is a naturally occurring compound and is the second most sig­
cell–mediated immune response, which consequently causes destruction nificant crystalline constituent of pongamia oil (Fig. 1). It contains a
of the pancreatic β cells. This response leads to decreased levels of in­ methoxy group along with enolic or phenolic hydroxyl moieties.
sulin secretion. On the other hand, type 2 diabetes is mostly associated Demethylation of pongamol with AlCl3 (aluminum chloride) affords nor-
with insulin resistance [19]. A survey on diabetic patients suggested that pongamol. However, an isomeric compound having no phenolic prop­
8.3% of adults have type 2 diabetes [20]. erties arises when pongamol is treated with hydroiodic acid (HI). On the
Medicinal plants have always been regarded as a source of bioactive other hand, treatment of pongamol with bromine affords a tetrabromo
compounds with potential health effects. Utilization of plants and plant-
based natural products is important for public health because they
include a variety of nutrients and are an excellent source of vitamins,
minerals, phenolics, fiber, antioxidants, and bioactive metabolites [21].
Since the beginning of civilization, plants having therapeutic qualities
have been employed in the treatment of various ailments. Numerous
research papers dealing with medicinal plants, which led to the devel­
opment of plant-based medications have been published [22]. In this
respect, the World Health Organization (WHO) estimates that about
80% of the world’s population uses herbal or plant-derived medications
for a variety of purposes [23]. Numerous studies from across the globe Fig. 1. Structure of pongamol.

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S. Jahan et al. Biomedicine & Pharmacotherapy 142 (2021) 112109

derivative, which further yields a tribromo compound upon boiling with comprised of a mixture of karanjic acid and o-methylkaranjic acid,
acetone. Moreover, pongamol is oxidized in the presence of potassium which based on solubility difference in water were largely separated, but
permanganate (KMnO4) and/or decomposes when treated with alkali, not fully purified. In contrast, methylation of pongamol yielded pure o-
resulting in the formation of benzoic acid. On the basis of the preceding methylkaranjic acid. Clearly, the primary product of fission was o-
discussion, pongamol is classified as a flavone derivative containing a methylkaranjic acid, although some of it was demethylated in alkali.
hydroxyl, methoxy, and ethylene double bond [30]. Similarly, the neutral fraction consisted of a mixture of acetophenone
Paper chromatography was used to investigate and separate a and a solid ketone (C11H19O3) comprising one methoxy group and
mixture resulting from treatment of pongamol with aqueous-alcoholic yielding no ferric reaction. Similarly, 5-acetyl-4-methoxybenzofuran
potassium hydroxide. Initially, products were separated into acid and was confirmed by its conversion into o-methylkaranjic acid, and is
neutral fractions. In acid fractions, benzoic acid was readily character­ synthesized from o-methylkaranjoyl chloride and ethyl acetoacetate. In
ized owing to its high solubility in water. The remaining fractions H2SO4 (sulfuric acid), Karanjic acid and its methyl ether produced

Fig. 2. General procedure for isolating pongamol from the seeds of P. pinnata.

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S. Jahan et al. Biomedicine & Pharmacotherapy 142 (2021) 112109

distinct colors. However, in absolute methyl alcoholic potassium hy­ and is dependent on the route of administration in animal models. In
droxide, the fission almost completely yielded a ketone and benzoic general, parenteral administration has greater bioavailability than other
acid. In conclusion, the above-mentioned results revealed that pongamol existing routes [47]. The bioavailability profile of pongamol was eval­
is benzoyl-o-methyl-karanjoyl methane (5-benzoylacetyl-4-methox­ uated using validated reversed-phase high-performance liquid chroma­
ybenzofuran) [40,41]. tography (RP-HPLC). Results of a study using Sprague-Dawley female
rats suggested that it has an excellent pharmacokinetic profile, as it had
3. Isolation of pongamol a good linear relationship of 0.02–2.92 µg/mL in plasma [48].

The following is an adopted procedure for the isolation of pongamol: 6. Pharmacological activities of pongamol
Petroleum ether (6 L) has been used for separation of the oil content
from Karanja seeds (1.5 kg) to afford 500 g of oil. the obtained seed oil 6.1. Antioxidant activity
was treated with methanol (1:2 v/v) for 6 h. Afterwards, the methanol
layer which was separated from the oil was collected, and the oily layer A free radical is an unstable substance that has an unpaired electron
was again macerated in methanol (1:2 v/v, 6 h); this procedure was in the atomic orbital; it is capable of exchanging the electron with other
repeated five times. Methanol extracts were pooled and vacuum- stable molecules and compounds. Free radicals can cause intracellular
concentrated until 30 mL volume remained. For karanjin crystalliza­ and extracellular changes, and thus cause cellular damage to the body.
tion, the concentrate was kept at room temperature (5.5 g). Then, 25 mL On the other hand, antioxidants are substances that donate or receive
of mother liquor was treated successively with 5 mL chloroform electrons from free radicals and neutralize them before they cause
(CHCl3), 10 mL acetic anhydride (CH3CO)2O, 15 mL diethyl ether cellular destruction [11]. In this regard, P. pinnata, which is rich in
(C2H5)2O, and 10 mL boron trifluoride etherate (BF3), respectively at pongamol, exhibits promising antioxidant activity. Wistar rats treated
0 ◦ C for 48 h. During this time, pongamol complexed and crystalized in with the leaf extract of the plant showed restricted lipid peroxidation
the form of yellow crystals from the solution. Filtration and air-drying and elevated superoxide dismutase (SOD) and catalase (CAT) activity
was used for the recovery of pongamol BF2 complex, which was after­ over time [37]. Rekha and colleagues determined the antioxidant ac­
wards hydrolyzed using methanol and 10% HCl (70 ◦ C, 6 h). The hy­ tivities of pongamol (main bioactive compound) isolated from karanja
drolysis reaction yielded the crude form of pongamol, which was run seed oil and its semi-synthetic analog dihydropongamol [42]. These two
against the standard pongamol using thin-layer chromatography (TLC) compounds displayed significant antioxidant activities using the DDPH
to afford 3.5 g crystalline pongamol (Fig. 2) [42]. (IC50 = 4.61 and 6.21 mg/mL), 2,2-azinobis-(3-ethylbenzothiazoline-6-­
sulfonate) (ABTS) (IC50 = 12.14 and 35.79 µg/mL), and ferric reducing
4. Sources of pongamol ability of plasma (FRAP) (0.61 and 0.21 mM Fe(II)/g) assays [42]. In a
similar fashion, Sajid and coworkers, [49] investigated the antioxidant
Pongamol, a major biologically active compound present in the seed properties of different parts (leaves, bark, and seeds) of P. pinnata. In this
oil of P. pinnata, is a polyphenolic chalcone that belongs to the flavonoid respect, the bark methanol extract exhibited maximum inhibitory ac­
family. Pongamol binds (− 5.79 kcal/mol) with soy LOX-1 via two tivity of linoleic acid peroxidation (69.2%) and radical scavenging
hydrogen bonds and exhibits antioxidant properties with an IC50 value ability (DPPH: IC50 = 3.21 µg/mL) as compared to leaves and seeds
of 12.2 μg/mL [42]. Hypoglycemic properties of pongamol derived from extracts [49]. Moreover, P. pinnata leaf extract (PPLE) and its bio­
the fruits of P. pinnata have been investigated in streptozotocin-induced synthesized nanoparticles (PPLEAgNPs) showed considerable antioxi­
diabetic rats, and in hyperglycemic, hyperlipidemic, and hyper­ dant activity in DPPH (IC50 = 176.9 and 167.3 µg/mL), ABTS (IC50 =
insulinemic db/db mice [43]. The plant grows wild in the coastal forests 157.9 and 130.8 µg/mL), superoxide anion (IC50 = 180.4 and
throughout India and beside watercourses and rivers. Currently, it is 152.6 µg/mL), and hydroxyl radical (IC50 = 131.1 and 111.4 µg/mL)
found in Australia, Florida, Hawaii, India, Malaysia, Oceania, the scavenging assays [50] (Table 2).
Philippines, and the Seychelles. The seed kernel yields 39% non-­
edible–grade fixed oil containing karanjin and pongamol [44]. Ponga­ 6.2. Antimicrobial activity
mol is naturally present in oil from karanja (P. glabra) fruits [45].
Pongamol is also isolated from Millettia pinnata, which is native to South Antimicrobials are any substance obtained naturally, synthetically,
and Southeast Asia, and is now grown all over the world. In order to or semi-synthetically that can destroy and inhibit the growth of micro­
examine the anticancer properties, series of oxazole and pyrazole de­ organisms. The antimicrobial activity of pongamol was evaluated
rivatives of pongamol have been designed and synthesized [46]. Shown through the disc diffusion method. Published research indicated that
in Table 1 are sources of pongamol. 200 µg/disc pongamol significantly inhibits both gram-positive and
gram-negative bacteria, including Bacillus subtilis, Staphylococcus aureus,
5. Bioavailability Escherichia coli, and Salmonella typhi [38]. Similarly, the bark extract of
P. pinnata has demonstrated maximum antimicrobial activity against
Bioavailability is a context where drug’s availability in the biological three different bacterial (P. aeruginosa, P. stutzeri, and E. coli) and three
system is assessed. It measures the rate and extent of the magnitude of fungal (A. orazae, A. niger, & F. solani) strains with highest inhibition
drugs that reach each compartment of the biological system. Bioavail­ zone of 22.6 mm and minimum MIC (minimum inhibitory
ability is closely associated with the pharmacokinetic aspect of a drug,
Table 2
Table 1 Pharmacological activities of pongamol.
Sources of pongamol.
Activity Subject Dose Effect Ref.
Species Family Plant Extract Amount Yield Ref.
Antioxidant Wistar rats, 400 mg/ Restricted initiation of [37]
parts (%)
Swiss mice kg superoxide
Pongamia Fabaceae Seeds Ethanol 750 g 12.5% [43] Antimicrobial – 200 μg/ Restricted growth of gram [38]
pinnata disc (+) and (− ) bacteria
Millettia Fabaceae Seeds Methanol 260 g 17.85% [71] Antidiabetic Albino male 250 mg/ ↓ blood glucose [39]
pinnata rats kg
Tephrosia Fabaceae Bark Ethanol 1000 g – [72] L6 skeletal 10 µm ↑glucose uptake in the [52]
purpurea muscle cells cells

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concentration) of 22 mg/mL [49] (Table 2). regard, Rao and coworkers reported that pongamol derivatives resulted
in differential sensitivity in different cell types in targeting ERK1
6.3. Anti-diabetic activity signaling [53]. However, these derivatives were effective in targeting
CDK2, suggesting a potential role for these drugs in targeting the cell
Diabetes is a disease, which is associated with inconsistency of blood cycle in IMR-32, HeLa, and Jurkat cancer cells in a dose-dependent
glucose levels in the body. Diabetes mellitus is divided into two types, manner [54]. In a similar fashion, Sriphana and colleagues reported
type 1 and type 2 [51]. When pongamol was administered into that pongamol exhibits weak cytotoxicity against KB, NCI-H187, and
streptozotocin-induced diabetic rats at a dose of 250 mg/kg, it decreased Vero cells, with IC50 values ranging from 28.44 to 114.44 µM [55].
glucose levels in a dose-dependent manner [39]. Another study reported Another study revealed that P. pinnata, which contains 40% pongamol,
that pongamol exhibits anti-hyperglycemic activity where it elevated exerts cytotoxic properties against Daphnia, although the seed powder
glucose uptake in L6 skeletal muscle cells through the extract was more effective [56]. Another research group reported that
PI3K–AKT-dependent pathway [52] (Table 2). Derris indica, which contains pongamol derivatives, exhibits high
toxicity against KKU-M156 (cholangiocarcinoma) and HepG2 (human
6.4. Anti-cancer activity hepatoma) cells [57]. In addition, research findings showed that TP
pongamol exhibits cytotoxicity with IC50 of 152.4 and 158.71 µmol/L,
The anti-cancer activity of pongamol has been extensively explored respectively [58].
using various cell signaling pathways and cancer cell lines. Numerous in
vitro attempts have been reported for pongamol and pongamol- 6.4.1. Effect of pongamol on breast cancer
containing plants as anticancer agents (Table 3 and Fig. 3). In this Sharma and co-workers investigated the cancer chemo-preventive
potential of the flavonoid-rich medicinal plant, P. pinnata (L.) Pierre.
Table 3 These researchers found that the methanol extract of its seeds inhibits
Oncogenic activity of pongamol. CYP1A1 in CYP1A1-overexpressing normal human HEK293 cells with
IC50 of 0.6 µg/mL, whereas its secondary metabolites, pongapin/lan­
Activity Test Dose Key effects Ref.
subject ceolatin B, inhibited CYP1A1 with IC50 of 20 nM. In addition, pongamol
inhibited CYP1A1 with IC50 of 4.4 µM while the semi-synthetic pyrazole
Antitumor IMR-32, 20, 50, 100, 150, Differential sensitivity [54]
HeLa, 200 μg in different cell types in derivative (P5b) showed nearly 10-fold enhanced effectiveness (IC50 =
Jurkat targeting the ERK1 0.49 μM). Moreover, these compounds blocked the cell cycle arrest at
cancer cell signaling. the G0–G1 phase for CYP1A1-overexpressing MCF-7 breast cancer cells,
line repressed the levels of cyclin-D1, and induced cellular senescence [33].
KB, MCF-7, 28.44–114.44 μM Weak cytotoxicity (IC50 [55]
In another study, Zand and colleagues reported that pongamol de­
NCI-H187, of 28.44–114.44 µM)
Vero cells rivatives significantly inhibit PSA production by BT-474 cells at the
Daphnia – Cytotoxic [56] highest tested concentration (10− 5 mol/L) [59].
KKU-M156 – high cytotoxicity [57]
and HepG2
6.4.2. Effect of pongamol on gastric cancer
cells
MCF-7 152.4 µmol/L, Cytotoxic against MCF- [58]
A recent study revealed that pongamol is effective against gastric
human 158.71 µmol/L 7 cells cancer cell lines. Within this context, Sharma and co-workers reported
cancer that P. pinnata, which contains 40% pongamol, causes reduction of acid
cells output followed by decrease in gastric mucosal cell shedding along with
Breast MCF-7 0.49 µM, 4.4 μM Decreases expression of [33]
elevation in mucin secretions and mucosal glycoprotein content without
cancer breast the CYP1A1
cancer affecting cellular proliferation. Application of P. pinnata caused signifi­
cells, cant reduction in elevated gastric mucosal lipid peroxidation (LPO), NO,
HEK293 and SOD levels initiated by cold restraint stress (CRS) and brought them
cells
5
back to normal levels. Additionally, P. pinnata caused an increase in GSH
BT-474 10− mol/L Significantly blocked [59]
cells PSA
and CAT contents that were reduced by CRS and ethanol [35]. Another
Gastric Rats 200 mg/kg Decrease acid output [57] study reported that 1–20 mg/kg aqueous extract of Tephrosia purpurea
cancer and increases mucin containing pongamol has an effect on ethanol-induced gastric ulcer, and
secretion and mucosal 5–20 mg/kg pongamol-containing plant extract conferred
glycoprotein, while
dose-dependent protection against indomethacin-induced ulcers [60].
decreasing gastric
mucosal cell shedding Furthermore, pongamol-containing extract acted as an anti-Helicobacter
without any effect on pylori agent in terms of the efficacy of its bacteriostatic and bactericidal
cell proliferation. activity at stomach acidic pH [61]. Published research showed that
1–20 mg/kg, Inhibits ethanol- [35]. H. pylori is a causative factor in the development of stomach cancer [62].
5–20 mg/kg induced gastric ulcer
pro-healing action and [61]
Thus, by reducing acid production and inhibiting H. pylori, pongamol
improves collagen plays a very important role in preventing gastric cancer. Others have
maturation reported that pongamol-containing extract exhibits definite pro-healing
Has significant anti- [63] action and improves collagen maturation by cross-linking, and increases
ulcer effect
dry granuloma weight. Results of another investigation suggest that
Liver Rats Lowers AST, ALT, ALP, [63]
cancer and total bilirubin pongamol-containing plant extract exerts significant anti-ulcer activity,
levels which could either be due to a cytoprotective action or by strengthening
Prevented cellular [58] the gastric and duodenal mucosa and thus enhancing mucosal defense
leakage and the loss of [63].
functional integrity of
liver cell.
Prostate PC-3 10− 5
mol/L Inhibited PSA [59] 6.4.3. Effect of pongamol on liver cancer
cancer prostate production In CCl4-induced hepatotoxic rats, orally administered T. purpurea
cancer that is rich in pongamol, exhibited a significant decrease in aspartate
cells
aminotransferase (AST), alkaline phosphatase (ALP), alanine

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S. Jahan et al. Biomedicine & Pharmacotherapy 142 (2021) 112109

Fig. 3. Mechanisms accounting for the anti-cancer effects of pongamol.

transaminase (ALT), and total bilirubin [63]. Similarly, according to properties, and displays central nervous system (CNS)-depressant ac­
another in vitro study, alcoholic extract exerted significant hydroxyl tivity [44]. Investigation of P. pinnata (L.) fruits has shown that it is a
(OH) radical scavenging properties. Additionally, in liver cell mem­ plant with health promoting properties, wherein pongamol is one of its
branes, the extract prevented leakage of cells and functional integrity compounds. Pongamol has been used in traditional medicine for treating
loss initiated by several hepatotoxic agents [59]. several ailments such as hemorrhoids, skin diseases, and wounds in
numerous countries [68]. Pongamol from P. pinnata seed oil is also used
6.4.4. Effect of pongamol on prostate cancer for skin diseases such as psoriasis, eczema, and vitiligo. However,
Flavonoids are now being investigated for their role in preventing further investigations are required before conclusions can be drawn.
prostate cancer [64]. Prostate specific antigen (PSA) has been used as a
biomarker to identify prostate cancer [65]. In this regard, numerous 7. Toxicological study
androgen response elements (AREs) are found in the promoter/enhancer
region of PSA. If additional transcription factors are present, the gene is Subacute toxicity of pongamol isolated from P. pinnata (Family:
transcribed to mRNA, and subsequently translated to the secreted PSA Papilionaceae) was studied in Long-Evans rats. Studies included (a)
protein. Inhibition of any of these processes reduces PSA protein syn­ gross observations such as changes in body weight, (b) hematological
thesis and secretion. profiles (total count of red blood cells, white blood cells, platelet, dif­
ferential white blood cell count, erythrocyte sedimentation rate, and
hemoglobin percentage), (c) blood biochemical parameters (serum
6.5. Other biological activities of pongamol
glutamate oxaloacetate transaminase, serum glutamate pyruvate trans­
aminase, serum alkaline phosphatase, serum bilirubin, creatinine, and
In addition to exhibiting anti-inflammatory and anticancer effects,
urea), and (d) histopathology of the liver, kidney, heart, and lung of
pongamol also has numerous traditional uses. Pongamol showed anti-
control and experimental groups of rats. Changes in body weight, the
hyperglycemic effect in diabetic rats [43]. In this context, Tamrakar
hematological, and biochemical parameters were not statistically sig­
and coworkers investigated the effect of pongamol isolated from
nificant after administration of 300 µg/rat/day of pongamol for 14
P. pinnata fruits on GLUT-4 translocation and glucose uptake in skeletal
consecutive days as compared with the control [69].
muscle cells [66]. Moreover, pongamol exerted anticonvulsant, antiox­
Similarly, histopathological results revealed no abnormality in the
idant, dyslipidemic, and antiviral properties, suggesting that it is a po­
liver, kidney, heart, and lung of experimental rats. These results suggest
tential moiety with multiple biological effects [67]. Additionally,
that pongamol could be safely used for chronic toxicological studies and
pongamol from P. pinnata seeds exhibits antibacterial and insecticidal

6
S. Jahan et al. Biomedicine & Pharmacotherapy 142 (2021) 112109

clinical trials. In addition, different biological effects such as induction Writing – original draft. Zidan Khan: Conceptualization, Investigation,
of quinone reductase, anticonvulsant effect, and CNS depressant activity Writing – original draft. Ashraful Alam: Conceptualization, Investiga­
have been reported for pongamol. Results of subacute toxicity studies tion, Writing – original draft. Anees Ahmed Khalil: Formal analysis,
showed no abnormalities in body weight, blood hematological and Resources. Abdur Rauf: Formal analysis, Writing – review & editing.
biochemical parameters, and on histopathological slides. Results of Abu Montakim Tareq: Conceptualization, Formal analysis, Investiga­
these biological effects of pongamol and its toxicological studies suggest tion. Firzan Nainu: Formal analysis, Writing – review & editing. Syed
that pongamol is safe for chronic toxicological studies and clinical trials Mohammed Tareq: Formal analysis. Talha Bin Emran: Formal anal­
[69]. In acute and subacute studies, a significant decrease in serum ysis, Investigation, Resources, Writing – review & editing. Muneeb
glucose levels was observed due to administration of petroleum ether Khan: Resources. Ishaq N. Khan: Resources. Polrat Wilairatana:
extract of P. pinnata stem bark (25–400 mg/kg). In addition, the Conceptualization, Writing – review & editing. Mohammad S.
anti-hyperglycemic effects of administered extracts revealed an onset at Mubarak: Writing – review & editing.
2 h and peak effects at 6 h. Similarly, the effects were sustainable for
24 h in the case of 400 mg/kg dose. In the subacute study, an Conflict of interest statement
anti-hyperglycemic effect was observed on day 21. In extract-treated
mice, the body weight was not reduced as compared to that in the There are no conflicts of interest to declare.
vehicle group, whereas in the oral glucose tolerance test (OGTT),
increased glucose utilization was observed [70]. Data availability

8. Conclusions and future prospects The datasets supporting the conclusions of this study are included
within the article.
In summary, pongamol is a promising candidate for further phar­
macological development, as it shows a variety of effects against Acknowledgment
different diseases, including cancer. Its efficacy against breast, stomach,
liver, and prostate cancer has been studied in vivo and in vitro. Pon­ Not applicable.
gamol also exerts cytotoxic activity against various cell lines, which
bolsters the claims that this compound can be a potential anticancer References
agent. In other studies, pongamol from P. pinnata leaf exhibited anti­
oxidant activity in Wistar rats, where it inhibits the activity of lacto­ [1] M.A. Seyed, I. Jantan, S.N.A. Bukhari, K. Vijayaraghavan, A comprehensive review
peroxidase (LPO) activity and acts against oxidative stress (OS). on the chemotherapeutic potential of piceatannol for cancer treatment, with
mechanistic insights, J. Agric. Food Chem. 64 (4) (2016) 725–737.
Pongamol is also effective in terms of its antimicrobial aspects, where it [2] J.A. Thomson, J. Itskovitz-Eldor, S.S. Shapiro, M.A. Waknitz, J.J. Swiergiel, V.
can restrict both gram-negative and gram-positive bacteria. S. Marshall, J.M. Jones, Embryonic stem cell lines derived from human blastocysts,
In addition, pongamol can be very effective against diabetes, a major Science 282 (5391) (1998) 1145–1147.
[3] G.M. Cooper, R.E. Hausman, The development and causes of cancer. The Cell: A
issue in modern medicine; it decreased the blood glucose levels in Molecular Approach, 2nd, ASM Press, Washington, D.C., 2000.
streptozotocin-induced diabetic rats in a dose-dependent manner and [4] M.C. Casimiro, M. Crosariol, E. Loro, Z. Li, R.G. Pestell, Cyclins and cell cycle
increased glucose uptake in L6 skeletal muscle cells via a definite control in cancer and disease, Genes Cancer 3 (11–12) (2012) 649–657.
[5] J.W. Koten, J.P. Neijt, B.A. Zonnenberg, W. Den Otter, The difference between
pathway. Research findings also suggest that pongamol exhibits anti- benign and malignant tumours explained with the 4-mutation paradigm for
inflammatory effects. In this respect, lipoxygenase is an important carcinogenesis, Anticancer Res. 13 (4) (1993) 1179–1182.
marker of the inflammatory response in the body. Pathogen invasion of [6] F. Bray, J. Ferlay, I. Soerjomataram, R.L. Siegel, L.A. Torre, A. Jemal, Global cancer
statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36
the body causes the lipid bilayer to convert into arachidonic acid. Then, cancers in 185 countries, CA Cancer J. Clin. 68 (6) (2018) 394–424.
lipoxygenase catalyzes the production of leukotrienes, lipoxins, and [7] S.K. Saha, S.B. Lee, J. Won, H.Y. Choi, K. Kim, G.-M. Yang, A.A. Dayem, S.-G. Cho,
chemokines. An in vitro study revealed that 72.21 μM pongamol inhibits Correlation between oxidative stress, nutrition, and cancer initiation, Int. J. Mol.
Sci. 18 (7) (2017) 1544.
the median maximum concentration of lipoxygenase and thus reduces
[8] V. Lobo, A. Patil, A. Phatak, N. Chandra, Free radicals, antioxidants and functional
the initiation of pro-inflammatory cytokines. Similarly, an in vivo toxi­ foods: impact on human health, Pharmacogn. Rev. 4 (8) (2010) 118–126.
cological study of pongamol that evaluated its safety profile showed no [9] M.S. Brewer, Natural antioxidants: sources, compounds, mechanisms of action, and
distortion from the hepatic, urinary, cardiac, and pulmonary aspects. potential applications, Compr. Rev. Food Sci. Food Saf. 10 (4) (2011) 221–247.
[10] A. Phaniendra, D.B. Jestadi, L. Periyasamy, Free radicals: properties, sources,
Based on the preceding findings, it is clear that pongamol is a potential targets, and their implication in various diseases, Indian J. Clin. Biochem. 30 (1)
medicinal agent or a lead compound against various diseases. However, (2015) 11–26.
further research is required to provide more insight into its pharmaco­ [11] V. Lobo, A. Patil, A. Phatak, N. Chandra, Free radicals, antioxidants and functional
foods: impact on human health, Pharmacogn. Rev. 4 (8) (2010) 118–126.
kinetics and pharmacodynamics, and unfold its mechanism as a me­ [12] M. Abudawood, H. Tabassum, B. Almaarik, A. Aljohi, Interrelationship between
dicinal agent to bridge the existing knowledge gap. In this regard, more oxidative stress, DNA damage and cancer risk in diabetes (Type 2) in Riyadh, KSA,
experiments with animals and or human subjects may shed more light Saudi J. Biol. Sci. 27 (1) (2020) 177–183.
[13] U. Asmat, K. Abad, K. Ismail, Diabetes mellitus and oxidative stress-a concise
about the possible use of this plant-based chemical as a chemothera­ review, Saudi Pharm. J. 24 (5) (2016) 547–553.
peutic agent. [14] S. Doron, S.L. Gorbach, Bacterial infections: overview, Int. Encycl. Public Health
(2008) 273–282.
[15] M. Karamanou, A. Protogerou, G. Tsoucalas, G. Androutsos, E. Poulakou-
Ethics approval and consent to participate Rebelakou, Milestones in the history of diabetes mellitus: the main contributors,
World J. Diabetes 7 (1) (2016) 1–7.
Not applicable. [16] A.T. Kharroubi, H.M. Darwish, Diabetes mellitus: the epidemic of the century,
World J. Diabetes 6 (6) (2015) 850–867.
[17] G. Da Silva Xavier, The cells of the islets of langerhans, J. Clin. Med. 7 (3) (2018)
Consent for publication 54.
[18] G. Wilcox, Insulin and insulin resistance, Clin. Biochem. Rev. 26 (2) (2005) 19–39.
[19] American Diabetes Association, Diagnosis and classification of diabetes mellitus,
Not applicable.
Diabetes Care 33 (Suppl. 1) (2010) S62–S69.
[20] A.T. Kharroubi, H.M. Darwish, Diabetes mellitus: the epidemic of the century,
CRediT authorship contribution statement World J. Diabetes 6 (6) (2015) 850–867.
[21] M.A. Haque, I. Jantan, S.N.A. Bukhari, Tinospora species: an overview of their
modulating effects on the immune system, J. Ethnopharmacol. 207 (2017) 67–85.
Shamima Jahan: Conceptualization, Investigation, Writing – orig­ [22] A.A. Reza, M.A. Haque, J. Sarker, M.S. Nasrin, M.M. Rahman, A.M. Tareq, Z. Khan,
inal draft. Md. Hasan Mahmud: Conceptualization, Investigation, M. Rashid, M.G. Sadik, T. Tsukahara, Antiproliferative and antioxidant potentials

7
S. Jahan et al. Biomedicine & Pharmacotherapy 142 (2021) 112109

of bioactive edible vegetable fraction of Achyranthes ferruginea Roxb. in cancer [47] S.-C. Chow, Bioavailability and bioequivalence in drug development, Wiley Int.
cell line, Food Sci. Nutr. 9 (2021) 3777–3805. Rev. Comput. Stat. 6 (4) (2014) 304–312.
[23] A.M. Agbor, S. Naidoo, A review of the role of African traditional medicine in the [48] N. Shejawal, S. Menon, S. Shailajan, Bioavailability of karanjin from Pongamia
management of oral diseases, Afr. J. Tradit. Complement. Altern. Med. 13 (2) pinnata L. in Sprague dawley rats using validated RP-HPLC method, J. Appl.
(2016) 133–142. Pharm. Sci. 4 (3) (2014) 10.
[24] A.J. Alonso-Castro, M.L. Villarreal, L.A. Salazar-Olivo, M. Gomez-Sanchez, [49] Z.I. Sajid, F. Anwar, G. Shabir, G. Rasul, K.M. Alkharfy, A.-H. Gilani, Antioxidant,
F. Dominguez, A. Garcia-Carranca, Mexican medicinal plants used for cancer antimicrobial properties and phenolics of different solvent extracts from bark,
treatment: pharmacological, phytochemical and ethnobotanical studies, leaves and seeds of Pongamia pinnata (L.) Pierre, Molecules 17 (4) (2012)
J. Ethnopharmacol. 133 (3) (2011) 945–972. 3917–3932.
[25] R. Gerson-Cwilich, A. Serrano-Olvera, A. Villalobos-Prieto, Complementary and [50] R.S. Priya, D. Geetha, P.S. Ramesh, Antioxidant activity of chemically synthesized
alternative medicine (CAM) in Mexican patients with cancer, Clin. Transl. Oncol. 8 AgNPs and biosynthesized Pongamia pinnata leaf extract mediated AgNPs–a
(3) (2006) 200–207. comparative study, Ecotoxicol. Environ. Saf. 134 (2016) 308–318.
[26] N.J. Jacobo-Herrera, F.E. Jacobo-Herrera, A. Zentella-Dehesa, A. Andrade-Cetto, [51] A. Sapra, P. Bhandari, Diabetes Mellitus, StatPearls [Internet], 2020.
M. Heinrich, C. Pérez-Plasencia, Medicinal plants used in Mexican traditional [52] A.K. Tamrakar, N. Jaiswal, P.P. Yadav, R. Maurya, A.K. Srivastava, Pongamol from
medicine for the treatment of colorectal cancer, J. Ethnopharmacol. 179 (2016) Pongamia pinnata stimulates glucose uptake by increasing surface GLUT4 level in
391–402. skeletal muscle cells, Mol. Cell. Endocrinol. 339 (1–2) (2011) 98–104.
[27] P. Maduna, The role of traditional medicine in the treatment of diabetes mellitus, [53] A. Pelter, R.S. Ward, E.V. Rao, N.R. Raju, Perkin transactions 1, 8-substituted
S. Afr. Med. 24 (10) (2006) 574–577. flavonoids and 3′ -substituted 7-oxygenated chalcones from Tephrosia purpurea,
[28] P. Scartezzini, E. Speroni, Review on some plants of Indian traditional medicine J. Chem. Soc. (1981) 2491–2498.
with antioxidant activity, J. Ethnopharmacol. 71 (1–2) (2000) 23–43. [54] R.R. Rao, V. Chaturvedi, K.S. Babu, P.P. Reddy, V.R.S. Rao, P. Sreekanth, A.
[29] M. Ginovyan, M. Petrosyan, A. Trchounian, Antimicrobial activity of some plant S. Sreedhar, J.M. Rao, Synthesis and anticancer effects of pongamol derivatives on
materials used in Armenian traditional medicine, BMC Complement. Altern. Med. mitogen signaling and cell cycle kinases, Med. Chem. Res. 21 (5) (2012) 634–641.
17 (1) (2017) 1–9. [55] U. Sriphana, C. Yenjai, S. Tungnoi, J. Srirapa, A. Junsongduang, Flavonoids from
[30] S. Rangaswami, T. Seshadri, Chemistry of Pongamol. Part I, Proceedings of the Milletia leucantha and their cytotoxicity, Nat. Prod. Commun. 13 (8) (2018)
Indian Academy of Sciences-Section A, Springer, Netherlands, 1942, pp. 417–423. 961–962.
[31] S. Mahli, S. Basu, K. Sinha, N. Banerjee, Pharmacological effects of karanjin and [56] R. Shirsat, A. Rai, In vitro cytotoxic studies of Pongamia pinnata Pierre using
pongamol [from seed oil of Pongamia pinnata], Indian J. Anim. Sci. 59 (6) (1989) aqueous extracts of seed powder and callus, Octa J. Biosci. 3 (1) (2015).
657–660. [57] A. Sharma, R. Kaur, J.K. Katnoria, R. Kaur, A.K. Nagpal, Family Fabaceae: A Boon
[32] R. Sharma, S. Mehan, S. Kalra, D. Khanna, Tephrosia purpurea-a magical herb with for Cancer Therapy, Biotechnology and Production of Anti-Cancer Compounds,
blessings in human biological system, Int. J. Recent Adv. Pharm. Res. 3 (3) (2013) Springer, Netherlands, 2017, pp. 157–175.
12–22. [58] S. Palbag, B.K. Dey, N.K. Singh, Ethnopharmacology, phytochemistry and
[33] R. Sharma, I.S. Williams, L. Gatchie, V.R. Sonawane, B. Chaudhuri, S.B. Bharate, pharmacology of Tephrosia purpurea, Chin. J. Nat. Med. 12 (1) (2014) 1–7.
Furanoflavones pongapin and lanceolatin B blocks the cell cycle and induce [59] R.S.R. Zand, D.J.A. Jenkins, T.J. Brown, E.P. Diamandis, Flavonoids can block PSA
senescence in CYP1A1-overexpressing breast cancer cells, Bioorg. Med. Chem. 26 production by breast and prostate cancer cell lines, Clin. Chim. Acta 317 (1–2)
(23–24) (2018) 6076–6086. (2002) 17–26.
[34] R.S.R. Zand, D.J. Jenkins, T.J. Brown, E.P. Diamandis, Flavonoids can block PSA [60] J.G. Kusters, A.H.M. Van Vliet, E.J. Kuipers, Pathogenesis of Helicobacter pylori
production by breast and prostate cancer cell lines, Clin. Chim. Acta 317 (1–2) infection, Clin. Microbiol. Rev. 19 (3) (2006) 449–490.
(2002) 17–26. [61] E.K. Akkol, U. Koca, I. Peşin, D. Yılmazer, G. Toker, E. Yeşilada, Exploring the
[35] J. Park, E. Ernst, Ayurvedic Medicine for Rheumatoid Arthritis: A Systematic wound healing activity of Arnebia densiflora (Nordm.) Ledeb. by in vivo models,
Review, Seminars in Arthritis and Rheumatism, Elsevier, Netherlands, 2005, Ind. Crop. Prod. 124 (1) (2009) 137–141.
pp. 705–713. [62] N. Matsukura, M. Onda, K. Yamashita, Helicobacter pylori in peptic ulcer and
[36] S. Deshpande, G. Shah, N. Parmar, Antiulcer activity of Tephrosia purpurea in rats, gastric cancer, Cancer Chemother. 22 (2) (1995) 169–178.
Indian J. Pharmacol. 35 (3) (2003) 168–172. [63] S.S. Deshpande, G.B. Shah, N.S. Parmar, Antiulcer activity of Tephrosia purpurea
[37] D. Dwivedi, M. Dwivedi, S. Malviya, V. Singh, Evaluation of wound healing, anti- in rats, Indian J. Pharmacol. 35 (3) (2003) 168–172.
microbial and antioxidant potential of Pongamia pinnata in wistar rats, J. Tradit. [64] S.S. Strom, Y. Yamamura, C.M. Duphorne, M.R. Spitz, R.J. Babaian, P.C. Pillow, S.
Complement. Med. 7 (1) (2017) 79–85. D. Hursting, Phytoestrogen intake and prostate cancer: a case-control study using a
[38] M.A. Baki, G. Sadik, K.S.H. Mondal, M.A. Mosaddik, M.M. Rahman, new database, Nutr. Cancer 33 (1) (1999) 20–25.
Methylkarranjic acid and Pongamol from Derris indica seeds and their antibacterial [65] S. Cabarkapa, M. Perera, S. McGrath, N. Lawrentschuk, Prostate cancer screening
activity, Dhaka Univ. J. Pharm. Sci. 6 (1) (2007) 9–13. with prostate-specific antigen: a guide to the guidelines, Prostate Int. 4 (4) (2016)
[39] A.K. Tamrakar, P.P. Yadav, P. Tiwari, R. Maurya, A.K. Srivastava, Identification of 125–129.
pongamol and karanjin as lead compounds with antihyperglycemic activity from [66] A.K. Tamrakar, N. Jaiswal, P.P. Yadav, R. Maurya, A.K.J.M. Srivastava, Pongamol
Pongamia pinnata fruits, J. Ethnopharmacol. 118 (3) (2008) 435–439. from Pongamia pinnata stimulates glucose uptake by increasing surface GLUT4
[40] - S. Narayanaswamy, S. Rangaswami, T. Seshadri. Chemistry of Pongamol. Part II, level in skeletal muscle cells, Mol. Cell. Endocrinol. 339 (1–2) (2011) 98–104.
Part II, J. Chem. Soc, United Kingdom, 1954, pp. 1871–1873. [67] F.E. Mouafi, M.M. Elkomy, M.M.A. Elsoud, Optimization of Lovastatin production
[41] L.M. Al Muqarrabun, N. Ahmat, S.A. Ruzaina, N.H. Ismail, I. Sahidin, Medicinal under sub-merged fermentation and it’s effect on cholesterol blood level in rats,
uses, phytochemistry and pharmacology of Pongamia pinnata (L.) Pierre: a review, J. Innov. Pharm. Biol. Sci. 3 (4) (2016) 33–42.
J. Ethnopharmacol. 150 (2) (2013) 395–420. [68] L. Al Muqarrabun, N. Ahmat, S. Ruzaina, N. Ismail, I. Sahidin, Medicinal uses,
[42] M. Rekha, B. Bettadaiah, T.S. Kanya, K.J. Govindaraju, A feasible method for phytochemistry and pharmacology of Pongamia pinnata (L.) Pierre: a review,
isolation of pongamol from karanja (Pongamia pinnata) seed and its anti- J. Ethnopharmacol. 150 (2) (2013) 395–420.
inflammatory activity, Ind. Crop. Prod. 154 (2020), 112720. [69] M.A. Baki, A. Khan, M.A.A. Al-Bari, A. Mosaddik, G. Sadik, K.J. Mondal, Sub-acute
[43] A.K. Tamrakar, P.P. Yadav, P. Tiwari, R. Maurya, A.K. Srivastava, Identification of toxicological studies of pongamol isolated from Pongamia pinnata, Merit Res. J.
pongamol and karanjin as lead compounds with antihyperglycemic activity from Med. Med. Sci. 2 (2) (2007) 53–57.
Pongamia pinnata fruits, Ind. Crop. Prod. 118 (3) (2008) 435–439. [70] S.L. Badole, S.L. Bodhankar, Investigation of antihyperglycaemic activity of
[44] S. Mahli, S. Basu, K. Sinha, N.J. Banerjee, Pharmacological effects of karanjin and aqueous and petroleum ether extract of stem bark of Pongamia pinnata on serum
pongamol [from seed oil of Pongamia pinnata], Indian J. Anim. Sci. 59 (6) (1989) glucose level in diabetic mice, J. Ethnopharmacol. 123 (1) (2009) 115–120.
657–660. [71] H. Perumalsamy, M.J. Jang, J.-R. Kim, M. Kadarkarai, Y.-J. Ahn, Larvicidal activity
[45] V. Gore, P. Satyamoorthy, Determination of pongamol and karanjin in karanja oil and possible mode of action of four flavonoids and two fatty acids identified in
by reverse phase HPLC, Anal. Lett. 13 (2000) 337–346. Millettia pinnata seed toward three mosquito species, Parasites Vectors 8 (1)
[46] R.R. Rao, V. Chaturvedi, K.S. Babu, P.P. Reddy, V.R.S. Rao, P. Sreekanth, (2015) 237.
A. Sreedhar, J.M. Rao, Synthesis and anticancer effects of pongamol derivatives on [72] V.S. Parmar, J.S. Rathore, R. Jain, D.A. Henderson, J.F. Malone, Occurrence of
mitogen signaling and cell cycle kinases, Med. Chem. Res. 21 (5) (2012) 634–641. pongamol as the enol structure in Tephrosia purpurea, Phytochemistry 28 (2)
(1989) 591–593.