Karanjin

Parasit Vectors. 2015 Apr 19;8:237.

Larvicidal activity and possible mode of action of four flavonoids and two fatty acids identified in Millettia pinnata seed toward three mosquito species.[Pubmed: 25928224 ]

Aedes aegypti and Aedes albopictus and Culex pipiens pallens mosquitoes transmit dengue fever and West Nile virus diseases, respectively. This study was conducted to determine the toxicity and mechanism of action of four flavonoids and two fatty acids from Millettia pinnata (Fabaceae) seed as well as six pure fatty acids and four fatty acid esters toward third instar larvae from insecticide-susceptible C. pipiens pallens and A. aegypti as well as wild A. albopictus. Efficacy of 12 experimental liquid formulations containing M. pinnata seed methanol extract and hydrodistillate (0.5-10.0% liquids) was also assessed.
METHODS AND RESULTS:
The contact toxicities of all compounds and 12 formulations were compared with those of two larvicides, temephos and fenthion and the commercial temephos 200 g/L emulsifiable concentrate (EC). The possible mode of larvicidal action of the constituents was elucidated using biochemical methods. Larval mortality and cAMP level were analyzed by the Bonferroni multiple-comparison method. Potent toxicity was produced by Karanjin, oleic acid, karanjachromene, linoleic acid, linolenic acid, pongamol, pongarotene, and elaidic acid toward C. pipiens pallens larvae (24 h LC50, 14.61-28.22 mg/L) and A. aegypti larvae (16.13-37.61 mg/L). Against wild A. albopictus larvae, oleic acid (LC50, 18.79 mg/L) and Karanjin (35.26 mg/L) exhibited potent toxicity. All constituents were less toxic than either temephos or fenthion. Structure-activity relationship indicates that the degree of saturation, the side chain length, and the geometric isomerism of fatty acids appear to play a role in determining the fatty acid toxicity. Acetylcholinesterase (AChE) is the main site of action of the flavonoids, oleic acid, and palmitic acid. The mechanism of larvicidal action of elaidic acid, arachidic acid, and behenic acid might be due to interference with the octopaminergic system. Linoleic acid and linolenic acid might act on both AChE and octopaminergic receptor. M. pinnata seed extract or hydrodistillate applied as 10% liquid provided 100% mortality toward the three mosquito species larvae and the efficacy of the liquids was comparable to that of temephos 200 g/L EC.
CONCLUSIONS:
Further studies will warrant possible applications of M. pinnata seed-derived products as potential larvicides for the control of mosquito populations.

Eur J Pharmacol. 2011 Nov 16;670(1):22-8.

Karanjin from Pongamia pinnata induces GLUT4 translocation in skeletal muscle cells in a phosphatidylinositol-3-kinase-independent manner.[Pubmed: 21939653]

Insulin-stimulated glucose uptake in skeletal muscle is decreased in type 2 diabetes due to impaired translocation of insulin-sensitive glucose transporter 4 (GLUT4) from intracellular pool to plasma membrane. Augmenting glucose uptake into this tissue may help in management of type 2 diabetes.
METHODS AND RESULTS:
Here, the effects of an identified antihyperglycemic molecule, Karanjin, isolated from the fruits of Pongamia pinnata were investigated on glucose uptake and GLUT4 translocation in skeletal muscle cells. Treatment of L6-GLUT4myc myotubes with Karanjin caused a substantial increase in the glucose uptake and GLUT4 translocation to the cell surface, in a concentration-dependent fashion, without changing the total amount of GLUT4 protein and GLUT4 mRNA. This effect was associated with increased activity of AMP-activated protein kinase (AMPK). Cycloheximide treatment inhibited the effect of Karanjin on GLUT4 translocation suggesting the requirement of de novo synthesis of protein. Karanjin-induced GLUT4 translocation was further enhanced with insulin and the effect is completely protected in the presence of wortmannin. Moreover, Karanjin did not affect the phosphorylation of AKT (Ser-473) and did not alter the expression of the key molecules of insulin signaling cascade.
CONCLUSIONS:
We conclude that Karanjin-induced increase in glucose uptake in L6 myotubes is the result of an increased translocation of GLUT4 to plasma membrane associated with activation of AMPK pathway, in a PI-3-K/AKT-independent manner.

Evid Based Complement Alternat Med. 2011;2011:747246.

Gastroprotective Properties of Karanjin from Karanja (Pongamia pinnata) Seeds; Role as Antioxidant and H, K-ATPase Inhibitor.[Pubmed: 21799691 ]

Plant extracts are the most attractive sources of newer drugs and have been shown to produce promising results for the treatment of gastric ulcers.
METHODS AND RESULTS:
Karanjin, a furano-flavonoid has been evaluated for anti-ulcerogenic property by employing adult male albino rats. Karanjin (>95% pure) was administered to these rats in two different concentrations, that is, 10 and 20 mg kg(-1) b.w. Ulcers were induced in the experimental animals by swim and ethanol stress. Serum, stomach and liver-tissue homogenates were assessed for biochemical parameters. Karanjin inhibited 50 and 74% of ulcers induced by swim stress at 10 and 20 mg kg(-1) b.w., respectively. Gastric mucin was protected up to 85% in case of swim stress, whereas only 47% mucin recovery was seen in ethanol stress induced ulcers. H(+), K(+)-ATPase activity, which was increased 2-fold in ulcer conditions, was normalized by Karanjin in both swim/ethanol stress-induced ulcer models. Karanjin could inhibit oxidative stress as evidenced by the normalization of lipid peroxidation and antioxidant enzyme (i.e., catalase, peroxidase and superoxide dismutase) levels. Karanjin at concentrations of 20 mg kg(-1) b.w., when administered orally for 14 days, did not indicate any lethal effects.
CONCLUSIONS:
There were no significant differences in total protein, serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase and alkaline phosphatase between normal and Karanjin-treated rats indicating no adverse effect on major organs. During treatment schedule, animals remained as healthy as control animals with normal food and water intake and body weight gain.

J Ethnopharmacol. 2008 Aug 13;118(3):435-9.

Identification of pongamol and karanjin as lead compounds with antihyperglycemic activity from Pongamia pinnata fruits.[Pubmed: 18572336 ]

To identify pongamol and Karanjin as lead compounds with antihyperglycemic activity from Pongamia pinnata fruits.
METHODS AND RESULTS:
Streptozotocin-induced diabetic rats and hyperglycemic, hyperlipidemic and hyperinsulinemic db/db mice were used to investigate the antihyperglycemic activity of pongamol and karangin isolated from the fruits of Pongamia pinnata. In streptozotocin-induced diabetic rats, single dose treatment of pongamol and Karanjin lowered the blood glucose level by 12.8% (p<0.05) and 11.7% (p<0.05) at 50mg /kg dose and 22.0% (p<0.01) and 20.7% (p<0.01) at 100mg/kg dose, respectively after 6h post-oral administration. The compounds also significantly lowered blood glucose level in db/db mice with percent activity of 35.7 (p<0.01) and 30.6 (p<0.01), respectively at 100mg/kg dose after consecutive treatment for 10 days. The compounds were observed to exert a significant inhibitory effect on enzyme protein tyrosine phosphatase-1B (EC 3.1.3.48).
CONCLUSIONS:
The results showed that pongamol and karangin isolated from the fruits of Pongamia pinnata possesses significant antihyperglycemic activity in Streptozotocin-induced diabetic rats and type 2 diabetic db/db mice and protein tyrosine phosphatase-1B may be the possible target for their activity. CONCLUSION: The results showed that pongamol and karangin isolated from the fruits of Pongamia pinnata possesses significant antihyperglycemic activity in Streptozotocin-induced diabetic rats and type 2 diabetic db/db mice and protein tyrosine phosphatase-1B may be the possible target for their activity.

Phytother Res. 2014 Aug;28(8):1188-95.

Prevention of arthritis markers in experimental animal and inflammation signalling in macrophage by Karanjin isolated from Pongamia pinnata seed extract.[Pubmed: 24399783]

Karanjin, the furanoflavonoid reported to possess gastroprotective and anti-diabetic properties, was investigated against experimental arthritis and its molecular signalling in inflammation was explored in macrophages.
METHODS AND RESULTS:
Karanjin was isolated from hexane extract of Pongamia pinnata seeds and was evaluated on arthritis markers in adjuvant induced arthritis model (AIA) in two doses (per oral; 10 mg/kg/day and 20 mg/kg/day). Karanjin dose dependently reduced collagen and cartilage breakdown markers viz. urinary hydroxyproline and glucosamine, respectively, serum lysosomal enzymes responsible for articular cartilage damage, and major proinflammatory cytokine TNFα, secreted by macrophages involved in articular inflammation and destruction. Karanjin also prevented joint damage as evidenced from arthritis score, radiographic and histopathological analysis. To delineate the molecular target of Karanjin, in vitro study on LPS induced macrophages were performed at calibrated non toxic doses (4 μg/mL and 6 μg/mL). Karanjin reduced TNFα production and also showed potent inhibitory effect on nitric oxide and reactive oxygen species production which is generally induced by TNFα from activated macrophages. NF-κB, the key regulator of TNFα signalling during inflammation was significantly suppressed by Karanjin.
CONCLUSIONS:
Our study for the first time highlights the anti-inflammatory role of Karanjin in experimental arthritis model as well as on macrophage signalling, thereby depicting its probable mechanism of action.

Pflugers Arch. 2018 Jun 30.

Natural and synthetic flavonoids, novel blockers of the volume-regulated anion channels, inhibit endothelial cell proliferation.[Pubmed: 29961148]

Natural flavonoids are ubiquitous in dietary plants and vegetables and have been proposed to have antiviral, antioxidant, cardiovascular protective, and anticancer effects. Volume-regulated anion channels (VRACs), which are essential for cell volume regulation, have been proposed to play a key role in cell proliferation and migration, apoptosis, transepithelial transport, and cancer development.
METHODS AND RESULTS:
In this study, we screened a group of 53 structurally related natural flavonoids and three synthetic flavonoids for their inhibitory activities on VRAC currents. A whole-cell patch technique was used to record VRAC currents in the human embryonic kidney (HEK) 293 and human umbilical vein endothelial (HUVEC) cells. The 5'-bromo-2-deoxyuridine (BrdU) assay technique was used to investigate cell proliferation. At 100 μM, 34 of 53 compounds significantly inhibited hypotonic extrasolution-induced VRAC currents by > 50% in HEK293 cells. Among these compounds, luteolin, baicalein, eupatorin, galangin, quercetin, fisetin, Karanjin, Dh-morin, genistein, irisolidone, and prunetin exhibited the highest efficacy for VRAC blockade (the mean inhibition > 80%) with IC50s of 5-13 μM and Emaxs of about 87-99%. We also studied the effects of three synthetic flavonoids on VRAC currents in HEK293 cells. Flavoxate showed high inhibition efficacy toward VRAC currents (IC50 = 2.3 ± 0.3 μM; Emax = 91.8% ± 2.7%). Finally, these flavonoids inhibited endogenous VRAC currents and cell proliferation in endothelial cells.
CONCLUSIONS:
This study demonstrates that natural and synthetic flavonoids are potent VRAC current inhibitors, and VRAC inhibition by flavonoids might be responsible for their anti-angiogenic effects.

Biol Res. 2015 Jul 26;48:40.

Effects of karanjin on cell cycle arrest and apoptosis in human A549, HepG2 and HL-60 cancer cells.[Pubmed: 26209237]

METHODS AND RESULTS:
We have investigated the potential anticancer effects of Karanjin, a principal furanoflavonol constituent of the Chinese medicine Fordia cauliflora, using cytotoxic assay, cell cycle arrest, and induction of apoptosis in three human cancer cell lines (A549, HepG2 and HL-60 cells). MTT cytotoxic assay showed that Karanjin could inhibit the proliferation and viability of all three cancer cells. The induction of cell cycle arrest was observed via a PI (propidium iodide)/RNase Staining Buffer detection kit and analyzed by flow cytometry: Karanjin could dose-dependently induce cell cycle arrest at G2/M phase in the three cell lines. Cell apoptosis was assessed by Annexin V-FITC/PI staining: all three cancer cells treated with Karanjin exhibited significantly increased apoptotic rates, especially in the percentage of late apoptosis cells.
CONCLUSIONS:
Karanjin can induce cancer cell death through cell cycle arrest and enhance apoptosis. This compound may be effective clinically for cancer pharmacotherapy.

Indian J Pharmacol. 2017 Mar-Apr;49(2):161-167.

Effect of karanjin on 2,4,6-trinitrobenzenesulfonic acid-induced colitis in Balb/c mice.[Pubmed: 28706329]

METHODS AND RESULTS:
Colitis was induced in the Balb/c mice by rectal administration of 2% solution of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in 50% methanol. Karanjin (>98% pure) was administered in two different concentrations 100 and 200 mg/kg and sulfasalazine (100 mg/kg) as reference for 7 consecutive days to colitic mice. On the 8 day, mice were euthanized and degree of inflammation was assessed by macroscopic, microscopic, histology and biochemical estimation of myeloperoxidase (MPO), nitric oxide (NO), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) level were measured. Karanjin significantly and dose dependently ameliorate the macroscopic damage, histological changes such as cellular infiltration, tissue necrosis, mucosal and submucosal damage as compared to the TNBS control group. Karanjin reduces the activity of MPO, depressed MDA, and NO level and helps in restoring the level of CAT, SOD, and GSH to normal when compared to the TNBS colitis group.
CONCLUSIONS:
Result of the present study indicates that Karanjin has the potential to cure colitis induced by intracolonic administration of TNBS. RESULTS: Karanjin significantly and dose dependently ameliorate the macroscopic damage, histological changes such as cellular infiltration, tissue necrosis, mucosal and submucosal damage as compared to the TNBS control group. Karanjin reduces the activity of MPO, depressed MDA, and NO level and helps in restoring the level of CAT, SOD, and GSH to normal when compared to the TNBS colitis group. CONCLUSION: Result of the present study indicates that Karanjin has the potential to cure colitis induced by intracolonic administration of TNBS.

Ayu. 2017 Jan-Jun;38(1-2):76-81.

Anti-Alzheimer activity of isolated karanjin from Pongamia pinnata (L.) pierre and embelin from Embelia ribes Burm.f.[Pubmed: 29861598 ]

The aim of this study is to find out the anti-Alzheimer's activity of isolated Karanjin and embelin.
METHODS AND RESULTS:
Karanjin isolated from Pongamia pinnata (L.) pierre and embelin from Embelia ribes Burm.f. and their purity was confirmed by ultraviolet spectrophotometric and Thin layer chromatography based study. Anti-Alzheimer's activity of isolated compounds were evaluated through elevated plus maze and Morris water maze model on Swiss albino mice. Diazepam (1 mg/kg body weight, intraperitoneally) was used for the induction of Alzheimer's like effects (amnesia) on Swiss albino mice and piracetam (200 mg/kg body weight, oral) used as a standard treatment. In EPM, embelin and Karanjin decrease the transfer latency time in dose dependent manner and escape latency time in MWM method. A significant (P < 0.01) reduction in amnesia with an anti-Alzheimer's effect found when results of isolated compounds were compared with standard and vehicle control. Diazepam (1 mg/kg) treated group showed significant increase in escape latency and transfer latency when compared with vehicle control; which indicates impairment in learning and memory.
CONCLUSIONS:
Both isolated compounds and standard significantly reversed the amnesia induced by diazepam and improved learning and memory of mice in dose and time dependent manner. This study supports the ethnobotanical use of these two plants in India for the management of nerve or brain related problems.

Nat Prod Commun. 2009 Feb;4(2):209-10.

A new chalcone from Pongamia pinnata and its antioxidant properties.[Pubmed: 19370923]

METHODS AND RESULTS:
The root bark of Pongamia pinnata Pierre [syn P. glabra (family: Fabaceae)] afforded a new chalcone (karanjapin) and two known flavonoids, a pyranoflavonoid (karanjachromene) and a furanoflavonoid (Karanjin) The structure of karanjapin has been established from extensive 2D NMR spectral studies as beta,2'-dihydroxy-a,4'-dimethoxy-3,4-methylenedioxychalcone.
CONCLUSIONS:
Karanjapin and karanjachromene were found to possess significant antioxidant activity. This may play an important role in the pathogenesis of several diseases.