Karanjin

doi:10.1016/j.phytochem.2020.112641

Phytochemistry

Volume 183, March 2021, 112641

https://doi.org/10.1016/j.phytochem.2020.112641 Get rights and content

Highlights

•
Karanjin, a furanoflavonoid, is found in Leguminosae and the highest known yield is in Pongamia pinnata.
•
Various isolation approaches and protocols are compiled.
•
Testable probable biosynthetic pathways to karanjin are proposed and compared.
•
The broad-spectrum pharmacological and biopesticidal properties are highlighted.
•
The mechanism of karanjin-mediated effects at the molecular level are discussed.

Abstract

Karanjin [IUPAC: 3-methoxy-2-phenylfuro-(2,3-h-chrome-4-ol)], a bioactive furanoflavonoid and a potent biomolecule, was first isolated from Pongamia pinnata (L.). The crude extracts from root, leaf and seed having active constituent karanjin is highly valued in both traditional and modern knowledge systems. This review highlights, critically assesses, and presents the probable biosynthetic pathways of karanjin and its isolation methodologies with a view to actualizing its full potential. Karanjin exhibits multiple health benefits and applications, with evident anti-diabetic, anti-cancer, anti-inflammatory, anti-hyperglycemic, antioxidant, anti-colitis, anti-ulcer, and anti-Alzheimer properties. Consequently, the physiochemical properties and biological effects of karanjin have been detailed and analyzed. The efficacy of karanjin has been attenuated by toxicological studies that have proven karanjin to be non-toxic at physiological conditions as substantiated by in vitro and in vivo studies. In addition, the multiple insect repellent/insecticidal properties of karanjin and its availability as an acaricide/bio-insecticide have been reviewed. This review article underscores and endorses the immense potential for novel drug leads in various medicinal and industrial applications, suggesting a deeper insight into its metabolic fate, bioavailability, and cellular effects that await further investigations.

Graphical abstract

Introduction

Karanjin [IUPAC: 3-methoxy-2-phenylfuro-(2,3-h-chrome-4-ol); C₁₈H₁₂O₄] is a furanoflavonoid compound which readily forms a colorless needle-shaped crystal (158 °C; monoclinic crystal (Fig. 1). The flavonoid polyphenol backbone present in furanoflavonoids increases sensitivity to ambient changes, altering biological activity through modifications in solubility, hydrophobicity, and spectroscopic properties (Voicescu et al., 2014). The introduction of a methyl group, significantly impacts the photophysical and photochemical behavior in furanoflavonoids (Christoff et al., 1996). Similarly, the structure of karanjin and its functional groups impart hydrophobicity and semipolarity, besides facilitating solubility in various solvents like dimethyl sulfoxide (DMSO), ethanol, methanol, benzene, and petroleum ether etc. Karanjin belongs to the flavone subgroup of flavonoid compounds and is characterized by benzoyl and cinnamoyl backbone with a furan ring and methoxy substituent groups (Zsila et al., 2003; Singh et al., 2016). Ultraviolet (UV)-Visible absorption data derived from karanjin substantiates the presence of these moieties by two main absorption bands around 261 nm (Band I) and 309 nm (Band II) representing cinnamoyl and benzoyl, respectively (Zsila et al., 2003). In addition, molar extinction coefficients (ε) of karanjin have been evaluated as 7380 M⁻¹cm⁻¹ (Arshad et al., 2013). Karanjin also exhibits solvatochromic shift characteristics dependent on the properties of the solubilizing media. Therefore, the intrinsic UV–Visible absorption and fluorescence properties of karanjin can be utilized as their own ‘signature’ for characterizing the solute-solvent interactions. This would be very useful in understanding and providing initial insights into other potential applications of karanjin. Consequently, the physicochemical properties of karanjin have been summarized to provide a clear perspective from PubChem (National Center for Biotechnology Information) (Table 1).

Section snippets

Distribution of karanjin

Karanjin is characteristic of Leguminosae and have been reported in roots of several legumes like Tephrosia purpurea (L.) Pers. (Kumar and Gehlot, 2012), Fordia cauliflora Hemsl. (Fan et al., 2013; Guo et al., 2015), Millettia pulchra var. laxior (Dunn) Z. Wei (Fan et al., 2013), Lonchocarpus latifolius (Willd.) DC. (Magalhaes et al., 2000), Millettia pachycarpa Benth. (Shao et al., 2001), and Desmodium sequax Wall. (Gomes et al., 1981). It is well documented that Pongamia pinnata (L.) Pierre

Isolation of karanjin

The first ever isolation and structure determination of karanjin from P. pinnata was reported by Prof. Limaye in 1925, which became a trademark compound of this plant species (Limaye, 1925). Later, karanjin was isolated from other parts of the plant; such as root bark (Tanaka et al., 1992), flower (Talapatra et al., 1980), and stem bark (Saha et al., 1991).

Rao et al. (1939) attempted to isolate karanjin by distillation of P. pinnata oil, by precipitation from the alcoholic extract obtained by

Biosynthesis of karanjin

The core flavonoid biosynthetic pathway is highly conserved among plants and dependent on the species and set of enzymes to modify the basic skeleton to form different flavonoid subclasses. However, whole transcriptome sequencing of P. pinnata by Sreeharsha et al. (2016) resulted in hypothesizing possible metabolic and biosynthetic pathways. In total, 329 metabolic genes were characterized and found to be involved in specialized metabolites biosynthesis, transport, and catabolism. The KAAS

Pongamia pinnata

Pongamia pinnata (synonyms: Millettia pinnata, Cytisus pinnatus, Derris indica, Pongamia glabra; common names: Karanj, Indian Beech Tree, Honge Tree, Pongam Tree) is a perennial oleaginous legume (Leguminosae) with nitrogen-fixing capability and medicinal properties. This plant is native to the Indian subcontinent and grows on marginal land with no direct competition with food crops. It can thrive in areas with annual rainfall ranging from 500 to 2500 mm with the maximum temperature ranging

Pharmacological activity of karanjin

Studies have shown numerous pharmacological actions of crude extracts from different parts of P. pinnata; karanjin is believed to be one of the most studied and active ingredients to possess a broad spectrum of pharmacological properties. Interestingly, karanjin is well studied for a deeper understanding of its biological activity in both in vitro and in vivo systems. A recent review article has also highlighted the multiple biological properties of karanjin (Noor et al., 2020). Utilizing

Biopesticide property

Biopesticides are major components of integrated pest management (IPM) and serve as a potential alternative to their chemical counterparts. The important features of biopesticides are environmentally non-pollutive, renewable, indigenously available, and easily biodegradable; resulting in lower toxic residues and largely avoiding pollution problems associated with chemical pesticides.

Plants have many selective actions against a wide variety of pests and insects through various mechanisms,

Proposed mechanism of action responsible for various biological activities

Karanjin in both in-vitro and in-vivo modes has demonstrated a range of biological properties, which is mainly attributed to its anti-oxidant properties by inhibiting oxidative stress and free radical scavenging (Fig. 5). This antioxidant nature of karanjin might have played a central role in most of the biological effects. Several research groups have established that karanjin inhibits oxidative stress via regulating nitric oxide (NO), other ROS, and ATPases (Vismaya et al., 2010; Arshad et

Conclusion

The review highlights distribution and different methods for the isolation of karanjin. It also proposes two hypothetical biosynthetic pathways of karanjin. Karanjin may be synthesized via the classical phenylpropanoid or polyketide-type pathway. It may either form the chalcone backbone first or then incorporate the furan group; alternatively, acetophenone may act as a precursor moiety to which the chalcone backbone is subsequently added. The review underscores karanjin's potential as an

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

AS, GB, and NG thank the Ministry of Education (MoE) for students' fellowship. Authors thank the Library and Open Access facilities of the Institute for accessing journals during the preparation of the manuscript. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Dr. Anuma Singhis currently a freelance writer and earned her Ph.D. degree in Natural Product Chemistry from the Department of Biosciences and Bioengineering of Indian Institute of Technology Guwahati (IITG). Her research interest areas are medicinal chemistry and photophysics of the natural products isolated from plants and micro-organisms origin. She has coauthored 7 research articles in peer-reviewed journal and one book chapter.

References (85)

L.M.R. Al Muqarrabun et al.
Medicinal uses, phytochemistry and pharmacology of Pongamia pinnata (L.) Pierre: a review
J. Ethnopharmacol.
(2013)
M. Christoff et al.
Influence of methoxy substitution on flavonoid photophysics: a steady state and laser flash photolysis study
J. Photochem. Photobiol. Chem.
(1996)
N.W. Gaikwad et al.
Biosynthesis of β-substituted furan skeleton in the lower furanoterpenoids: a model study
Biochem. Biophys. Res. Commun.
(2002)
C.M.R. Gomes et al.
Systematic significance of flavonoids in Derris and Lonchocarpus
Biochem. Systemat. Ecol.
(1981)
S.A. Hawley et al.
Characterization of the AMP-activated protein kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase
J. Biol. Chem.
(1996)
N. Jaiswal et al.
Karanjin from Pongamia pinnata induces GLUT4 translocation in skeletal muscle cells in a phosphatidyl inositol-3-kinase-independent manner
Eur. J. Pharmacol.
(2011)
V. Kesari et al.
Physico-chemical characterization and microbial assay from seed oil of Pongamia pinnata, potential biofuel crop
Biomass Bioenergy
(2010)
A.F. Magalhaes et al.
Flavonoids from Lonchocarpus latifolius roots
Phytochemistry
(2000)
L. Margl et al.
Biosynthesis of benzofuran derivatives in root cultures of Tagetes patula via phenylalanine and 1-deoxy-D-xylulose 5-phosphate
Phytochemistry
(2005)
V.P. Pathak et al.
Isopongachromene, a chromenoflavone from Pongamia glabra seeds
Phytochemistry
(1983)

W.A. Peer et al.

Flavonoids and auxin transport: modulators or regulators?

Trends Plant Sci.

(2007)

D. Raghav et al.

Biochemical and toxicological investigation of karanjin, a bio-pesticide isolated from Pongamia seed oil

Pestic. Biochem. Physiol.

(2019)

D.S. Raie et al.

Application of quercetin and its bio-inspired nanoparticles as anti-adhesive agents against Bacillus subtilis attachment to surface

Mater. Sci. Eng. C

(2017)

M.M. Saha et al.

A chromenoflavanone and two caffeic esters from Pongamia glabra

Phytochemistry

(1991)

J.G. Scott et al.

Inhibition of cytochrome P450 6D1 by alkynylarenes, methylenedioxyarenes, and other substituted aromatics

Pestic. Biochem. Physiol.

(2000)

S.K. Talapatra et al.

Pongaglabol, a new hydroxyfuranoflavone, and aurantiamide acetate, a dipeptide from the flowers of Pongamia glabra

Phytochemistry

(1980)

A.K. Tamrakar et al.

Identification of pongamol and karanjin as lead compounds with antihyperglycemic activity from Pongamia pinnata fruits

J. Ethnopharmacol.

(2008)

T. Tanaka et al.

Flavonoids in root bark of Pongamia pinnata

Phytochemistry

(1992)

W.S. VanScyoc et al.

Calcium binding to calmodulin mutants monitored by domain-specific intrinsic phenylalanine and tyrosine fluorescence

Biophys. J.

(2002)

M. Verma et al.

Efficacy of karanjin and phorbol ester fraction against termites (Odontotermes obesus)

Int. Biodeterior. Biodegrad.

(2011)

Vismaya et al.

Extraction and recovery of karanjin: a value addition to karanja (Pongamia pinnata) seed oil

Ind. Crop. Prod.

(2010)

H. Yin et al.

The separation of flavonoids from Pongamia pinnata using combination columns in high-speed counter-current chromatography with a three-phase solvent system

J. Chromatogr., A

(2013)

H.M. Zhang et al.

Study on the interaction between cinnamic acid and lysozyme

J. Mol. Struct.

(2011)

F. Zsila et al.

Probing the binding of the flavonoid, quercetin to human serum albumin by circular dichroism, electronic absorption spectroscopy and molecular modelling methods

Biochem. Pharmacol.

(2003)

R.H. Abu‐Eittah et al.

The structure of cinnamic acid and cinnamoyl azides, a unique localized π system: the electronic spectra and DFT‐treatment

J. Quantum Chem.

(2012)

N. Arshad et al.

UV-absorption studies of interaction of karanjin and karanjachromene with ds. DNA: evaluation of binding and antioxidant activity

Cent. Eur. J. Chem.

(2013)

A. Bholane et al.

A critical review on Karanja (Pongamia pinnata) and its medicinal properties

J. Ayurveda Integr. Med. Sci.

(2020)

M. Bose et al.

Prevention of arthritis markers in experimental animal and inflammation signalling in macrophage by karanjin isolated from Pongamia pinnata seed extract

Phytother Res.

(2014)

M. Bose et al.

Suppression of NF-κB p65 nuclear translocation and tumor necrosis factor-α by Pongamia pinnata seed extract in adjuvant-induced arthritis

J. Immunot.

(2014)

N.V. Bringi

Non-Traditional Oilseeds and Oils in India

(1987)

V.V. Chopade et al.

Pongamia pinnata: phytochemical constituents, traditional uses and pharmacological properties: a review

Int. J. Green Pharm.

(2008)

L.G. Copping et al.

Natural products that have been used commercially as crop protection agents

Pest Manag. Sci.

(2007)

M. Damle et al.

Validated stability indicating method for Karanjin using HPTLC and HPLC

J. Pharmacogn. Phytochem.

(2018)

S.K. Dhanmane et al.

Isolation of karanjin from Pongamia pinnata and its identification by difference analytical techniques

Kurdistan J. Appl. Res.

(2018)

L.A. Donaldson et al.

Extractive distribution in Pseudotsuga menziesii: effects on cell wall porosity in sapwood and heartwood

IAWA J.

(2019)

M.L. Falcone Ferreyra et al.

Flavonoids: biosynthesis, biological functions, and biotechnological applications

Front. Plant Sci.

(2012)

L. Fan et al.

Determination of five flavonoids in different parts of Fordia cauliflora by ultra performance liquid chromatography/triple-quadrupole mass spectrometry and chemical comparison with the root of Millettia pulchra var

laxior. Chem. Cent. J.

(2013)

S. George et al.

Comparative efficacy of Annona squamosa linn. And Pongamia glabra vent. To Azadirachta indica A. Juss against mosquitoes

J. Vector Borne Dis.

(2005)

V.K. Gore et al.

Determination of pongamol and karanjin in karanja oil by reverse phase HPLC

Anal. Lett.

(2000)

J. Guo et al.

Effects of karanjin on cell cycle arrest and apoptosis in human A549, HepG2 and HL-60 cancer cells

Biol. Res.

(2015)

K.R. Harmandeep et al.

Efflux pump inhibitory activity of flavonoids isolated from Alpinia calcarata against methicillin-resistant Staphylococcus aureus

Biologia

(2016)

P. Irigaray et al.

Basic properties and molecular mechanisms of exogenous chemical carcinogens

Carcinogenesis

(2010)

Cited by (21)

Anti-tumor potential and mode of action of karanjin against breast cancer; an in-silico approach
2023, Arabian Journal of Chemistry
Karanjin is a furanoflavanoid first isolated from Pongamia pinnata and has been reported to possess a cytotoxic effect on various lung, breast, leukemia, and hepatoma cancers. However, the mechanism by which karanjin persists cytotoxic effect has yet not been unleashed for breast cancer. Hence, the present study aimed to predict a possible molecular mechanism of karanjin against breast cancer and its assessment on various breast cancer cell lines. We utilized multiple system biology tools like gene set enrichment analysis, gene ontology analysis, cluster analysis, molecular docking, molecular dynamic simulations, and MMPBSA analysis to predict the lead targets. Targets for breast cancer were retrieved from DisGeNet and Therapeutic Target Prediction and matched with targets of karanjin; further, they were subjected to gene enrichment and gene ontology analysis. Molecular docking was performed on all the matched targets; the top three complexes displaying the best binding affinity and the top three hub genes predicted via gene enrichment were selected for MD simulation. Cytotoxicity assay was performed on three different cell lines T47D, MDA-MB-468, and SKBR3, at different time exposures of 24, 48, and 96 hrs. Gene enrichment analysis predicted PI3KCA, PI3KCB, and EGFR as the top 3 hub genes and the PI3K-Akt signaling pathway as the majorly modulated pathway. Molecular docking revealed CYP1A1 to possess the least binding energy (-11.7 Kcal/mol) followed by AKR1C3 (-10.2 Kcal/mol), and CYP3A4 (-10 Kcal/mol). Further, molecular dynamic simulation and MMPBSA analysis displayed the complex of karanjin with CYP1A1 and PI3KCA to be the most stable. The cytotoxicity assay revealed karanjin to possess a more significant cytotoxic effect on SKBR3 cell lines with a dose-dependent increase in efficiency and also displayed an additive/synergistic effect on the three cell lines when used in combination with a tamoxifen/gefitinib. The predictions revealed that karanjin may possess anti-breast cancer potential by the modulation of proteins CYP1A1 and PIK3CA via the PI3K-Akt signaling pathway. However, the mechanism has been proposed via in-silico tools, which need further validation using wet lab protocols; this is the future scope of the study.
A critical review of Pongamia pinnata multiple applications: From land remediation and carbon sequestration to socioeconomic benefits
2022, Journal of Environmental Management
Pongamia pinnata (L.) Pierre (Pongamia) is a tree native to Southeast Asia. Recently, interest in Pongamia focused on its potential as a biofuel source as its seeds contain around 40% oil. However, Pongamia has multiple applications beyond biofuel production. It is a legume, can form symbiotic associations with mycorrhizal fungi, has been shown to be tolerant to drought, salinity, and heavy metals in soil, and has potential to mitigate climate change. Additionally, Pongamia oil has medicinal properties, can be used as biopesticide, insect repellent, to produce soap, and as a source of edible grade vegetable oil. The seed cake can be used as a source of bioenergy, food and feed protein, and organic fertiliser, and the flowers are a good source of pollen and nectar. Pongamia can also bring socio-economic benefits as its ability to restore degraded and contaminated land provides opportunities for local communities through novel valorisation pathways. These multiple applications have potential to form part of a circular bioeconomy in line with sustainable development goals. Although research on the multiple applications of Pongamia has grown considerably, knowledge gaps remain and these need to be addressed so that the full potential of Pongamia can be achieved. Further understanding of the mechanisms underlying its resilience to abiotic stresses, phytoremediation potential and biotic interactions should be a priority, and co-ordinated breeding efforts will be key. Here, we critically review the available literature on Pongamia and highlight gaps in knowledge in which future research should focus on to ensure that the full potential of this versatile tree can be achieved. We conclude that Pongamia can potentially form part of a circular bioeconomy and that harnessing the multiple applications of Pongamia in a holistic manner, with collaboration among key stakeholders, is crucial for the successful application of its benefits far beyond biofuel production.
Network analysis for elucidating the mechanisms of Shenfu injection in preventing and treating COVID-19 combined with heart failure
2022, Computers in Biology and Medicine
Citation Excerpt :
Surprisingly, some of these active compounds have been reported to possess profound pharmacological activities. For example, the evidence showed that karanjin suppressed inflammatory mediators production released by immune cells via its antioxidant activity and immune modulatory effects [43]. Deoxyandrographolide (DL = 0.31, AlogP = 3.02 and LogS = −3.51) was found to have anti-inflammatory activity by inhibiting the production of lipopolysaccharide-induced proinflammatory mediators, such as TNF-α and interleukin 6 (IL-6), and decreasing mRNA level of inducible nitric oxide synthase [44].
The emergence of the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to millions of infections and is exerting an unprecedented impact on society and economies worldwide. The evidence showed that heart failure (HF) is a clinical syndrome that could be encountered at different stages during the progression of COVID-19. Shenfu injection (SFI), a traditional Chinese medicine (TCM) formula has been widely used for heart failure therapy in China and was suggested to treat critical COVID-19 cases based on the guideline for diagnosis and treatment of COVID-19 (the 7th version) issued by National Health Commission of the People's Republic of China. However, the active components, potential targets, related pathways, and underlying pharmacology mechanism of SFI against COVID-19 combined with HF remain vague.
To investigate the effectiveness and possible pharmacological mechanism of SFI for the prevention and treatment of COVID-19 combined with HF.
In the current study, a network analysis approach integrating active compound screening (drug-likeness, lipophilicity, and aqueous solubility models), target fishing (Traditional Chinese Medicine Systems Pharmacology, fingerprint-based Similarity Ensemble Approach, and PharmMapper databases), compound-target-disease network construction (Cytoscape software), protein-protein interaction network construction (STRING and Cytoscape software), biological process analysis (STRING and Cytoscape plug-in Clue GO) and pathway analysis (Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis) was developed to decipher the active ingredients, potential targets, relevant pathways, and the therapeutic mechanisms of SFI for preventing and treating COVID-19 combined with HF.
Finally, 20 active compounds (DL ≥ 0.18, 1≤Alog P ≤ 5, and −5≤LogS ≤ −1) and 164 relevant targets of SFI were identified related to the development of COVID-19 combined with HF, which were mainly involved in three biological processes including metabolic, hemostasis, and cytokine signaling in immune system. The C-T-D network and reactome pathway analysis indicated that SFI probably regulated the pathological processes of heart failure, respiratory failure, lung injury, and inflammatory response in patients with COVID-19 combined with HF through acting on several targets and pathways. Moreover, the venn diagram was used to identify 54 overlapped targets of SFI, COVID-19, and HF. KEGG pathway enrichment analysis showed that 54 overlapped targets were highly enriched to several COVID-19 and HF related pathways, such as IL-17 signaling pathway, Th17 cell differentiation, and NF-kappa B signaling pathway.
A comprehensive network analysis approach framework was developed to systematically elucidate the potential pharmacological mechanism of SFI for the prevention and treatment of SFI against COVID-19 combined with HF. The current study may not only provide in-depth understanding of the pharmacological mechanisms of SFI, but also a scientific basis for the application of SFI against COVID-19 combined with HF.
Safety and toxicologic evaluation of Edible Pongamia Oil: A novel food ingredient
2022, Food and Chemical Toxicology
Citation Excerpt :
Historical reports on the toxicity of Pongamia pinnata, in general, are limited, with results often dependent upon the variable isolation and purification techniques of the seed and oil extracts. While early studies reporting behavioral changes in mice and rats (Mahli et al., 1989) and body weight changes in broiler chickens (Natanam et al., 1989) exist, more recent reports validating the bioavailability of the test substance using standardized oil isolation techniques (Shejawal et al., 2014; Ye et al., 2015), and its detoxification of furanoflavonoid fractions (Gandhi and Cherian, 2000), indicate pongamia oil's potential as an effective key ingredient with no demonstrable toxicity to humans or rats (Singh et al., 2021), or for oil-extracted presscake meal in broiler chickens (Husna et al., 2017), or ruminants (Raj et al., 2016). Gandhi and Cherian (2000) evaluated the acute toxicity of unextracted karanja oil with the same oil derived from an aqueous methanolic extract process.
Edible Pongamia Oil (EPO) was evaluated in an acute oral toxicity study, GLP 14-Day and 90-Day repeated dose isocaloric dietary toxicity studies in rats, and in vitro Bacterial Reverse Mutation, and in vivo Mammalian Bone Marrow Chromosome Aberration genotoxicity studies for potential use as a food ingredient. In a non-GLP acute study, an LD₅₀ > 5000 mg/kg was determined. Subacute 14-day repeated dose dietary administration of 0, 5, 10 and 15% oil revealed no adverse changes in clinical pathology, liver histology, body weight or weight gain, food consumption or food efficiency. In a 90-day dietary study fed 0, 2.5, 5.0, 7.5 and 10.0%, no mortalities, clinical or ophthalmologic signs, body weight, body weight gain, food consumption, food efficiency or Functional Observational Battery/Motor Activity changes occurred with EPO consumption, nor were there any adverse changes in hematology, clinical chemistry, coagulation, urinalysis, or thyroid hormone values. There were no adverse macroscopic, estrus cycle, histopathologic or spermatogenesis findings, or absolute or relative organ weight changes related to administration of EPO. The No-Adverse-Effect-Level (NOAEL) was 10% in the diet, the highest dose tested, equivalent to 5163 (male) and 6469 (female) mg/kg/day in rats. No mutagenic or clastogenic genotoxic potential was reported.
Global transcriptome analysis reveals partial estrogen-like effects of karanjin in MCF-7 breast cancer cells
2022, Gene
Citation Excerpt :
Karanjin is a furanoflavonoid occurring widely in Leguminosae. It produces a myriad of biological effects in vitro or in vivo (Singh et al., 2021). It has anti-hyperglycemic (Tamrakar et al., 2008), anti-inflammatory (Bose et al., 2014), anti-ulcer (Vismaya et al., 2011), and anti-colitis (Patel and Trivedi, 2017) effects in vivo, and anti-proliferative (Guo et al., 2015; Raghav et al., 2019; Roy et al., 2019), cell cycle inhibitory (Guo et al., 2015; Roy et al., 2019), ROS limiting (Roy et al., 2019), and glucose-uptake inducing effects in vitro (Jaiswal et al., 2011).
Karanjin, an abundantly occurring furanoflavonoid in edible and non-edible legumes, exerts diverse biological effects in vivo, and in vitro. Its potential as an anticancer agent is gaining traction following recent demonstrations of its anti-proliferative, cell cycle inhibitory, and pro-apoptotic effects. However, the genomic correlates of these activities are not known. In the present study we delineated the transcriptomic footprint of 10 μM karanjin in MCF-7 breast cancer cells, using next generation sequencing technology (RNA-seq). We show that karanjin-modulated gene-expression repertoire is enriched in several hallmark gene sets, which include early estrogen-response, and G2/M checkpoint genes. Genes modulated by karanjin overlapped with those modulated by 1 nM 17β-estradiol (E2), or 1 μM tamoxifen. The results suggest partial estrogen-like activity of karanjin, thereby presenting a caveat to its anticancer potential. Further investigations into its mechanisms of action are warranted to ascertain the true potential of karanjin in anticancer, or endocrine therapy.
Antioxidant, anti-tyrosinase and anti-inflammatory activities of 3,5-dihydroxy-4′,7-dimethoxyflavone isolated from the leaves of Alpinia nigra
2021, Phytomedicine Plus
Overexposure to sunlight and high UV radiation leads to uncontrolled melanin production in the skin, leading to hyperpigmentation and inflammatory diseases. Therefore, there is a need to discover safe and highly prospective drugs from natural sources. Previous studies have shown that leaves and rhizome extract of Alpinia nigra possesses antioxidant and anti-inflammatory activities. Among the components of the most bioactive methanol and ethyl acetate extract, flavones seem to be the most promising compound.
To evaluate the antioxidant, anti-tyrosinase and anti-inflammatory efficacy of 3,5-dihydroxy-4′,7-dimethoxyflavone (DHDM).
The flavone DHDM was isolated from A. nigra ethyl acetate leaf extract and characterized by multi spectroscopic techniques. The toxicity of DHDM was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The antioxidant and reactive oxygen species (ROS) inhibitory activity were determined by 2,2-Diphenyl-1-picrylhydrazy (DPPH) assay and by flow cytometry. Further, the anti-tyrosinase activity was evaluated by in silico (molecular docking), fluorescence, and enzyme kinetics studies. The anti-inflammatory activity was demonstrated by western blotting.
The cell viability assay with DHDM showed no inhibition at ≤200 µM concentration in THP-1 (human macrophage) and ≤80 µM in HaCaT (human keratinocyte) cell lines. Additionally, strong antioxidant properties and reduced ROS generation suggested prevention from oxidative damage and skin aging. Strong binding of DHDM to tyrosinase leading to the conformational change was revealed by fluorescence quenching studies and molecular docking. Further, the anti-tyrosinase activity of the isolated compound was observed at 42.5 µM (IC₅₀). Moreover, DHDM inhibited the expression of anti-inflammatory proteins like TNF-α and NF-κB.
The DHDM demonstrates the efficient antioxidant, anti-tyrosinase and anti-inflammatory potential, which could be developed for obtaining a new drug for the management of hyperpigmentation and inflammatory-related diseases.

View all citing articles on Scopus

Mr. Gaurav Bhattis currently a Ph.D. scholar in the BSBE Dept of IITG. His research area envisages phytochemistry, molecular endocrinology and gene expression. He is presently working on the isolation, drug discovery and therapeutics from the Karanj. He has coauthored 1 research article in Scientific Reports.

Mr. Nihal Gujreis a research scholar at Centre for Rural Technology, IITG. Currently working on integrated soil quality management for rural areas. He did his masters in environment management and M. Phil. in energy and environment studies. He is an artist, travelogue writer and passionate photographer. His work across multiple disciplines broadly addresses narratives of ecology and soil quality management.

Dr. Sudip Mitrais an Associate Professor at the Centre for Rural Technology (CRT), IITG. For the last two decades he has been working in the field of agro-ecotechnologies, natural resources management, climate change-vulnerability and adaptation at community level, soil quality management and green house gases management in agriculture sector. He is a Nehru-Fulbright Fellow and had a stint as visiting Professor at the University of California, Davis, USA. He is also a Lead India Fellow.

Dr. Rajaram Swaminathanis a professor at the Department of Biosciences and Bioengineering at Indian Institute of Technology Guwahati, Assam, India. His research interests include: Protein structure; Protein Charge Transfer Spectra (ProCharTS) and Consequences of macromolecular crowding inside living cells.

Dr. Anil Mukund Limayeis an Associate Professor in the BSBE of IITG. His research interest has been in areas of Molecular Endocrinology, Cancer Biology, and Regulation of Gene Expression and his group is trying to understand estrogen regulation of gene expression in the context of breast cancer. He has co-authored around 20 publications in journals of international repute, which include Gene, Scientific Reports and Molecular and Cellular Endocrinology.

Dr. Latha Ranganis currently Professor and the Head of the Department of Biosciences and Bioengineering (BSBE) of Indian Institute of Technology Guwahati (IITG). Her research interest has been in the areas of Applied Biodiversity using an integrative approach that has helped in tapping bio-resources of North East India from wilderness to mining 'omics'. She has coauthored around 100 publications in various peer-reviewed journals and several book chapters.

¹: Equal contribution.

View full text

ReviewKaranjin

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Distribution of karanjin

Isolation of karanjin

Biosynthesis of karanjin

Pongamia pinnata

Pharmacological activity of karanjin

Biopesticide property

Proposed mechanism of action responsible for various biological activities

Conclusion

Declaration of competing interest

Acknowledgments

J. Ethnopharmacol.

J. Photochem. Photobiol. Chem.

Biochem. Biophys. Res. Commun.

Biochem. Systemat. Ecol.

J. Biol. Chem.

Eur. J. Pharmacol.

Biomass Bioenergy

Phytochemistry

Phytochemistry

Phytochemistry

Trends Plant Sci.

Pestic. Biochem. Physiol.

Mater. Sci. Eng. C

Phytochemistry

Pestic. Biochem. Physiol.

Phytochemistry

J. Ethnopharmacol.

Phytochemistry

Biophys. J.

Int. Biodeterior. Biodegrad.

Ind. Crop. Prod.

J. Chromatogr., A

J. Mol. Struct.

Biochem. Pharmacol.

The structure of cinnamic acid and cinnamoyl azides, a unique localized π system: the electronic spectra and DFT‐treatment

J. Quantum Chem.

UV-absorption studies of interaction of karanjin and karanjachromene with ds. DNA: evaluation of binding and antioxidant activity

Cent. Eur. J. Chem.

A critical review on Karanja (Pongamia pinnata) and its medicinal properties

J. Ayurveda Integr. Med. Sci.

Prevention of arthritis markers in experimental animal and inflammation signalling in macrophage by karanjin isolated from Pongamia pinnata seed extract

Phytother Res.

Suppression of NF-κB p65 nuclear translocation and tumor necrosis factor-α by Pongamia pinnata seed extract in adjuvant-induced arthritis

J. Immunot.

Non-Traditional Oilseeds and Oils in India

Pongamia pinnata: phytochemical constituents, traditional uses and pharmacological properties: a review

Int. J. Green Pharm.

Natural products that have been used commercially as crop protection agents

Pest Manag. Sci.

Validated stability indicating method for Karanjin using HPTLC and HPLC

J. Pharmacogn. Phytochem.

Isolation of karanjin from Pongamia pinnata and its identification by difference analytical techniques

Kurdistan J. Appl. Res.

Extractive distribution in Pseudotsuga menziesii: effects on cell wall porosity in sapwood and heartwood

IAWA J.

Flavonoids: biosynthesis, biological functions, and biotechnological applications

Front. Plant Sci.

Determination of five flavonoids in different parts of Fordia cauliflora by ultra performance liquid chromatography/triple-quadrupole mass spectrometry and chemical comparison with the root of Millettia pulchra var

laxior. Chem. Cent. J.

Comparative efficacy of Annona squamosa linn. And Pongamia glabra vent. To Azadirachta indica A. Juss against mosquitoes

J. Vector Borne Dis.

Determination of pongamol and karanjin in karanja oil by reverse phase HPLC

Anal. Lett.

Effects of karanjin on cell cycle arrest and apoptosis in human A549, HepG2 and HL-60 cancer cells

Biol. Res.

Efflux pump inhibitory activity of flavonoids isolated from Alpinia calcarata against methicillin-resistant Staphylococcus aureus

Biologia

Basic properties and molecular mechanisms of exogenous chemical carcinogens

Carcinogenesis

Review
Karanjin