Abstract
Background: Drugs with post-prandial action constitute one of the main courses of treatments for diabetes.
Objective: In the present investigation, we have explored the α-amylase inhibitory potential of ethanolic extract of Cocos nucifera endocarp.
Methods: DNS based assay was done to assess the α-amylase inhibition potential of ethanolic extract. Phytochemical screening and GC-MS analysis were done in order to assess the chemical profiling of extract. In silico docking studies were done using VLife MDS 4.6 software and the probable molecules, predicted after GC-MS analysis, were docked with the co-crystallized (acarbose) tracked active site and rest all cavities of porcine pancreatic α-amylase (1OSE). ADMET analysis was done using StarDrop 6.4, Derek Nexus and P450 Modules from Optibrium Ltd. and LHASA Ltd.
Results: DNS based α-amylase assay indicated that the IC50 value of extract lies in the range of 63- 126 µg/ml and at higher doses, i.e. above 250 µg/ml, it has better α-amylase inhibition than the standard drug, acarbose. Phytochemical screening indicated that ethanolic extract is rich in alkaloids, tannins, flavonoids, saponins, triterpenes, glycosides, carbohydrates, terpenoids, quinones and lactones. Further, GC-MS analysis (where Similarity Index was > 90) predicted that the probable phytoconstituents present in the ethanolic extract are myristic acid, syringaldehyde, eugenol, vanillin, 2,4-di-tert-butylphenol, lauric acid, palmitic acid methyl ester and γ-sitosterol. γ-Sitosterol showed the strong affinity towards the active site which was tracked by a co-crystallized ligand along with cavity 1 and 2 while significant interactions were observed in case of co-crystallized tracked active site as well as cavity 4 of 1OSE. Ethanolic extract of C. nucifera has no hemolytic effect.
Conclusion: Its ability to effectively inhibit α-amylase may be attributed to the presence of the above probable molecules, which will be explored further.
Keywords: Coconut, hard shell, antidiabetic, hypoglycaemic activity, medicinal plant, ADMET studies.
Graphical Abstract
[1]
Nagappa, A.N.; Thakurdesai, P.A.; Venkat Rao, N.; Singh, J. Antidiabetic activity of Terminalia catappa Linn fruits. J. Ethnopharmacol., 2003, 88(1), 45-50.
[2]
WHO. Facts & figures about diabetes. Available at: http://www.who.int/diabetes/facts/en/
(Accessed December 30,
2015).
[3]
Gale, J. India’s diabetes epidemic cuts down millions who escape
poverty. Bloomberg, November 7 2010. Available at: https://www.bloomberg.com/news/articles/2010-11-07/india-s-deadly-diabetes-scourge-cuts-down-millions-rising-to-middle-class (Accessed June, 8, 2012);
[4]
Anonymous. China faces 'diabetes epidemic', research suggests.
BBC, March 25 2010. Available at: http://news.bbc.co.uk/2/hi/asia-pacific/8587032.stm (Accessed June 8, 2012).
[5]
Kleinfield, N.R. Modern ways open India’s doors to diabetes. New
York Times, September 13 2006. Available at: https://www.nytimes.com/2006/09/13/world/asia/13diabetes.html (Accessed June 8, 2012).
[6]
Avantika, R.; Sharma, J.; Singh, S. Rachana. Exploring antioxidant and anti-apoptotic mechanisms of Tinospora cordifolia. Indo Global J. Pharm. Sci., 2014, 4, 137.
[7]
Nag, P.; Singh, M. Role of plant derived alkaloids and polyphenols in prevention & treatment of alzheimer’s disease. Indo Global J. Pharm. Sci., 2014, 4, 165.
[8]
Saxena, K.; Dixit, P. Antimicrobial, antioxidant activities & phytochemical screening of F. benghalensis bark. Indo Global J. Pharm. Sci., 2014, 4, 184.
[9]
Kumari, P.; Sahal, D.; Jain, S.K.; Chauhan, V.S. Bioactivity guided fractionation of leaves extract of Nyctanthes arbor tristis (Harshringar) against P falciparum. PLoS One, 2012, 7(12), e51714.
[10]
Willcox, M.L.; Bodeker, G. Plant-based malaria control: Research
initiative on traditional antimalarial methods. Parasitol. Today
(Regul. Ed.),2000, 16(6), 220-221.
[11]
Bourdeix, R.; Konan, J.; N’Cho, Y. Coconut: a guide to traditional and improved varieties, Diversiflo; Franc: Montpellier, 2005.
[12]
Prades, A.; Dornier, M.; Diop, N.; Pain, J.P. Coconut water uses, composition and properties: A review. Fruits, 2012, 67, 87-107.
[13]
Singla, R. Review on the pharmacological properties of Cocos nucifera endocarp. WebmedCentral. Pharm. Sci., 2012. 3WMC003413.
[14]
Ediriweera, E.R.H.S. Medicinal uses of coconut (Cocos nucifera L.). Cocoinfo Int., 2003, 10, 11-21.
[15]
Bankar, G.R.; Nayak, P.G.; Bansal, P.; Paul, P.; Pai, K.S.R.; Singla, R.K.; Bhat, V.G. Vasorelaxant and antihypertensive effect of Cocos nucifera Linn. endocarp on isolated rat thoracic aorta and DOCA salt-induced hypertensive rats. J. Ethnopharmacol., 2011, 134(1), 50-54.
[16]
Singla, R.; Jaiswal, N.; Bhat, V.; Jagani, H. Antioxidant & antimicrobial activities of Cocos nucifera Linn. (Arecaceae) endocarp extracts. Indo Global J. Pharm. Sci., 2011, 1(4), 354-361.
[17]
Venkataraman, S.; Ramanujam, T.R.; Venkatasubbu, V.S. Antifungal activity of the alcoholic extract of coconut shell - Cocos nucifera Linn. J. Ethnopharmacol., 1980, 2(3), 291-293.
[18]
Oliveira, L.M.; Bevilaqua, C.M.L.; Costa, C.T.C.; Macedo, I.T.F.; Barros, R.S.; Rodrigues, A.C.M.; Camurça-Vasconcelos, A.L.F.; Morais, S.M.; Lima, Y.C.; Vieira, L.S.; Navarro, A.M. Anthelmintic activity of Cocos nucifera L. against sheep gastrointestinal nematodes. Vet. Parasitol., 2009, 159(1), 55-59.
[19]
Akinyele, T.A.; Okoh, O.O.; Akinpelu, D.A.; Okoh, A.I. In-vitro antibacterial properties of crude aqueous and n-hexane extracts of the husk of Cocos nucifera. Molecules, 2011, 16(3), 2135-2145.
[20]
Silva, R.R.; Oliveira e Silva, D.; Fontes, H.R.; Alviano, C.S.; Fernandes, P.D.; Alviano, D.S. Anti-inflammatory, antioxidant, and antimicrobial activities of Cocos nucifera var. typica. BMC Complement. Altern. Med., 2013, 13, 107.
[21]
Freitas, J.C.C.; Nunes-Pinheiro, D.C.S.; Pessoa, A.W.P.; Silva, L.C.R.; Girao, V.C.C.; Lopes-Neto, B.E.; Agostinho, M.S.; Abreu, C.R.A. Effect of ethyl acetate extract from husk fiber water of Cocos nucifera in leishmania brazilensis infected hamsters. Brazilian J. Pharmacogn., 2011, 21, 1006-1011.
[22]
Akinyele, T.A.; Akinpelu, D.A.; Okoh, A.I. In vitro antilisterial properties of crude aqueous and n-hexane extracts of the husk of Cocos nucifera. Afr. J. Biotechnol., 2011, 10, 8117-8121.
[23]
Alviano, D.S.; Rodrigues, K.F.; Leitão, S.G.; Rodrigues, M.L.; Matheus, M.E.; Fernandes, P.D.; Antoniolli, A.R.; Alviano, C.S. Antinociceptive and free radical scavenging activities of Cocos nucifera L. (Palmae) husk fiber aqueous extract. J. Ethnopharmacol., 2004, 92(2-3), 269-273.
[24]
Adebayo, J.O.; Santana, A.E.G.; Krettli, A.U. Evaluation of the antiplasmodial and cytotoxicity potentials of husk fiber extracts from Cocos nucifera, a medicinal plant used in Nigeria to treat human malaria. Hum. Exp. Toxicol., 2012, 31(3), 244-249.
[25]
Roopan, S.M. Rohit; Madhumitha, G.; Rahuman, A.A.; Kamaraj, C.; Bharathi, A.; Surendra, T.V. Low-cost and eco friendly phytosynthesis of silver nanoparticles using Cocos nucifera coir extract and its larvicidal activity. Ind. Crops Prod., 2013, 43, 631-635.
[26]
Esquenazi, D.; Wigg, M.D.; Miranda, M.M.F.S.; Rodrigues, H.M.; Tostes, J.B.F.; Rozental, S.; da Silva, A.J.; Alviano, C.S. Antimicrobial and antiviral activities of polyphenolics from Cocos nucifera Linn. (Palmae) husk fiber extract. Res. Microbiol., 2002, 153(10), 647-652.
[27]
Baheti, A.M.; Rathi, B.S.; Khandelwal, K.R.; Bodhankar, S.L. Diuretic activity of Cocos nucifera husk in rats. J. Nat. Rem., 2006, 6, 35-37.
[28]
Costa, C.T.C.; Bevilaqua, C.M.; Morais, S.M.; Camurça-Vasconcelos, A.L.F.; Maciel, M.V.; Braga, R.R.; Oliveira, L.M.B. Anthelmintic activity of Cocos nucifera L. on intestinal nematodes of mice. Res. Vet. Sci., 2010, 88(1), 101-103.
[29]
Komala, S.M.; Mohammed, M.M.; Varghese, R.; Sampath, K.K.P. Antibacterial potential of root and bark of Cocos nucifera Linn. against isolated urinary tract infection causing pathogens. Int. J. Pharma Bio Sci., 2011, 2, 489-500.
[30]
Preetha, P.P.; Girija, D.V.; Rajamohan, T. Effects of coconut water on carbohydrate metabolism and pancreatic pathology of alloxan induced diabetic rats. Eur. J. Integr. Med., 2013, 5, 234-240.
[31]
Ajeigbe, K.O.; Ndaman, Z.A.; Amegor, O.F.; Onifade, A.A.; Asuk, A.A.; Ibironke, G.F.; Olaleye, S.B. Anti-nociceptive and anti-inflammatory potential of coconut water (Cocos nucifera L.) in rats and mice. Aust. J. Basic Appl. Sci., 2011, 5, 1116-1122.
[32]
Chen, W.; Zhu, Q.; Xia, Q.; Cao, W.; Zhao, S.; Liu, J. Reactive oxygen species scavenging activity and DNA effect of fresh and naturally fermented coconut sap. J. Food Biochem., 2011, 35, 1381-1388.
[33]
Viswanathan, V.; Kesavan, R.; Kavitha, K.V.; Kumpatla, S. A pilot study on the effects of a polyherbal formulation cream on diabetic foot ulcers. Indian J. Med. Res., 2011, 134, 168-173.
[34]
Chikku, A.M.; Rajamohan, T. Dietary coconut sprouts beneficially modulates cardiac damage induced by isoproterenol in rats. Bangladesh J. Pharmacol., 2012, 7, 258-265.
[35]
Renjith, R.S.; Rajamohan, T. Protective and curative effects of Cocos nucifera inflorescence on alloxan-induced pancreatic cytotoxicity in rats. Indian J. Pharmacol., 2012, 44(5), 555-559.
[36]
Renjith, R.S.; Rajamohan, T. Young inflorescence of Cocos nucifera contributes to improvement of glucose homeostasis and antioxidant status in diabetic rats. Int. J. Diabetes Dev. Ctries., 2012, 32, 193-198.
[37]
Renjith, R.S.; Chikku, A.M.; Rajamohan, T. Cytoprotective, antihyperglycemic and phytochemical properties of Cocos nucifera (L.) inflorescence. Asian Pac. J. Trop. Med., 2013, 6(10), 804-810.
[38]
Naskar, S.; Mazumder, U.K.; Pramanik, G.; Saha, P.; Haldar, P.K.; Gupta, M. Evaluation of antinociceptive and anti-inflammatory activity of hydromethanol extract of Cocos nucifera L. Inflammopharmacology, 2013, 21(1), 31-35.
[39]
Pal, D.; Sarkar, A.; Gain, S.; Jana, S.; Mandal, S. CNS depressant activities of roots of Coccos nucifera in mice. Acta Pol. Pharm., 2011, 68(2), 249-254.
[40]
Sivakumar, M.K.; Moideen, M.M.; Varghese, R.; Sheik, B.; Dhanapal, C.K. Preliminary phytochemical screening and anti-bacterial activity of Cocos nucifera Linn. Roots. Res. J. Pharm. Biol. Chem. Sci., 2011, 2, 468-477.
[41]
Dowd, P.F.; Johnson, E.T.; Vermillion, K.E.; Berhow, M.A.; Palmquist, D.E. Coconut leaf activity toward generalist maize insect pests. Entomol. Exp. Appl., 2011, 141, 208-215.
[42]
Mehlhorn, H.; Al-Quraishy, S.; Al-Rasheid, K.A.S.; Jatzlau, A.; Abdel-Ghaffar, F. Addition of a combination of onion (Allium cepa) and coconut (Cocos nucifera) to food of sheep stops gastrointestinal helminthic infections. Parasitol. Res., 2011, 108(4), 1041-1046.
[43]
Al-Adhroey, A.H.; Nor, Z.M.; Al-Mekhlafi, H.M.; Amran, A.A.; Mahmud, R. Evaluation of the use of Cocos nucifera as antimalarial remedy in Malaysian folk medicine. J. Ethnopharmacol., 2011, 134(3), 988-991.
[44]
Kodangala, C.; Saha, S.; Kodangala, P. Phytochemical studies of aerial parts of the plant Leucas lavandulaefolia. Der Pharma Chem., 2010, 2, 434-437.
[45]
Singh, D.; Singh, P.; Gupta, A.; Solanki, S.; Sharma, E.; Nema, R. Qualitative estimation of the presence of bioactive compound in Centella asiatica: an important medicinal plant. Int. J. Life Sci. Med. Sci., 2012, 2, 5-7.
[46]
Xavier, J.; Johnson, N. A study on the phytochemical, pharmacological and anti-insecticidal activity of Leucas aspera (Willd.). Linn. Int. J. Biol. Pharm. Allied Sci., 2013, 2, 894-902.
[47]
Bhandary, S.K.; Kumari, S.N.; Bhat, V.S.; Sharmila, K.P.; Bekal, M.P. Preliminary phytochemical screening of various extracts of Punica granatum peel, whole fruit and seeds. Nitte Univ. J. Heal. Sci., 2012, 2, 34-38.
[49]
Ahuja, J.; Suresh, J.; Deep, A. Madhuri; Pratyusha; Ravi. Phytochemical screening of aerial parts of Artemisia parviflora Roxb.: A medicinal plant. Der Pharm. Lett., 2011, 3, 116-124.
[50]
Savithramma, N.; Rao, L.M.; Suhrulatha, D. Screening of medicinal plants for secondary metabolites. Middle East J. Sci. Res., 2011, 8, 579-584.
[52]
Akinjogunla, O.; Yah, C.; Eghafona, N.; Ogbemudia, F. Antibacterial activity of leave extracts of Nymphaea lotus (Nymphaeaceae) on methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Staphylococcus aureus (VRSA) isolated from clinical samples. Ann. Biol. Res., 2010, 1, 174-184.
[53]
Rao, L.M.; Savithramma, N. Phytochemical studies of Svensonia hyderobadensis (walp.) Mold: A rare medicinal plant. Der Pharm. Lett., 2011, 3, 51-55.
[54]
Gibbs, R. Chemotaxonomy of Flowering Plants, Vol.1 ed. McGill Queen’s University Press, Montreal and London, 1974.
[55]
Zahurul Haque, M.; Jalil, M.; Islam Badrul, M. Phyto-chemical and anti-bacterial screening of musabbar Prepared from Aloe Vera. J. Adv. Sci. Res., 2012, 3, 74-77.
[56]
Pradeep, A.; Dinesh, M.; Govindraj, A.; Vinothkumar, D.; Ramesh Babu, N. Phytochemical analysis of some important medicinal plants. Int. J. Biol. Pharm. Res., 2014, 5, 48-50.
[57]
Singla, R.K.; Singh, R.; Dubey, A.K. Important aspects of post-prandial antidiabetic drug. Curr. Top. Med. Chem., 2016, 16(23), 2625-2633.
[58]
Beutin, L.; Zimmermann, S.; Gleier, K. Rapid detection and isolation of shiga-like toxin (verocytotoxin)-producing Escherichia coli by direct testing of individual enterohemolytic colonies from washed sheep blood agar plates in the VTEC-RPLA assay. J. Clin. Microbiol., 1996, 34(11), 2812-2814.
[59]
RCSB Protein Data Bank. Available at: https://www.rcsb.org/pdb/home/home.do (Accessed January 1,
2016).
[60]
VLifeMDS: Molecular Design Suite, VLife Sciences Technologies
Pvt. Ltd. Pune, India, 2013. Available at: www.vlifesciences.com (Accessed January 1, 2016).
[61]
Singla, R.K.; Bhat, G. V. QSAR model for predicting the fungicidal action of 1,2,4-triazole derivatives against Candida albicans. J. Enzyme Inhib. Med. Chem., 2010, 25(5), 696-701.
[62]
Malleshappa, N.N.; Harun, M.P. A comparative QSAR analysis and molecular docking studies of quinazoline derivatives as tyrosine kinase (EGFR) inhibitors: A rationale approach to anticancer drug design. J. Saudi Chem. Soc., 2011, 17(4), 361-379.
[63]
Singla, R.K. Mechanistic evidence to support the anti-hepatitis B viral activity of multifunctional scaffold & conformationally restricted magnolol. Natl. Acad. Sci. Lett., 2014, 37(1), 45-50.
[64]
Igoli, J.O.; Gray, A.I.; Clements, C.J.; Kantheti, P.; Singla, R.K. Antitrypanosomal activity & docking studies of isolated constituents from the lichen Cetraria islandica: possibly multifunctional scaffolds. Curr. Top. Med. Chem., 2014, 14(8), 1014-1021.
[65]
Igoli, N.P.; Clements, C.J.; Singla, R.K.; Igoli, J.O.; Uche, N.; Gray, A.I. Antitrypanosomal activity & docking studies of components of Crateva adansonii DC leaves: novel multifunctional scaffolds. Curr. Top. Med. Chem., 2014, 14(8), 981-990.
[66]
Singla, R.K.; Paul, P.; Nayak, P.G.; Bhat, V.G. Investigation of anthramycin analogs induced cell death in MCF-7 breast cancer cells. Indo Global J. Pharm. Sci., 2012, 2, 383-389.
[67]
Singla, R.K. Homology modeling of MDR1 gene MDR1_ENTHI of E. histolytica & its molecular docking with anti-entamoeba histolytica agents. Curr. Top. Med. Chem., 2015, 15(11), 980-989.
[68]
Singla, R.K.; Scotti, L.; Dubey, A.K. In silico studies revealed multiple neurological targets for the antidepressant molecule ursolic acid. Curr. Neuropharmacol., 2017, 15(8), 1100-1106.
[69]
Aggarwal, B.; Singla, R.K.; Ali, M.; Singh, V.; Igoli, J.O.; Gundamaraju, R.; Kim, K.H. Triterpenic and monoterpenic esters from stems of Ichnocarpus frutescens and their drug likeness potential. Med. Chem. Res., 2015, 24, 1427-1437.
[70]
Singla, R.K. Editorial: In silico drug design and medicinal chemistry). Curr. Top. Med. Chem., 2015, 15(11), 971-972.
[71]
Singla, R.K.; Dubey, A.K. Pharmacokinetics and toxicological
profiling of surfactin A: An in silico approach. Mol2Net,2015,
1(B), 1-5.
[72]
Obidoa, O.; Joshua, P.E.; Eze, N.J. Phytochemical analysis of Cocos nucifera L. J. Pharm. Res., 2010, 3, 280-286.
[73]
Aina, V.O.; Saudatu, A.J.; Adewumi, A.A.J.; Ibrahim, L.J.; Yeruwan, P.A.; Hauwa, U.; Hauwa, M.S.H.; Amina, Z. Comparative phytochemical screening and physicochemical characterization of coconut (Cocos nucifera) oils from two different locations in Kaduna State, Nigeria. J. Pharm. Allied Sci., 2013, 9, 1653-1660.
[74]
Dyana, J.P.; Kanchana, G. Preliminary phytochemical screening of Cocos nucifera L. flowers. Int. J. Curr. Pharm. Res., 2012, 4, 62-63.
[75]
Okon, O.; Ubong, E.; Aniekeme-Abasi, I. Characterization and phytochemical screening of coconut (Cocos nucifera L.) Coir dust as a low cost adsorbent for waste water treatment. Elixir Appl. Chem., 2012, 47, 8961-8968.
[76]
Jelenkovic, L.; Jovanovic, V.S.; Palic, I.; Mitic, V.; Radulovic, M. In vitro screening of α-amylase inhibition by selected terpenes from essential oils. Trop. J. Pharm. Res., 2014, 13(9), 1421-1428.
[77]
Liang, Y.; Pei, F.; Wang, H.; Chen, S. Two alkaloids as α- amylase inhibitors: Enzyme kinetics and molecular modelling investigations. J. Chin. Pharm. Sci., 2015, 24(2), 80-87.
[78]
Nickavar, B.; Amin, G. Enzyme assay guided isolation of an α-amylase inhibitor flavonoid from Vaccinium arctostaphylos leaves. Iran. J. Pharm. Res., 2011, 10(4), 849-853.
[79]
da Silva, S.M.; Koehnlein, E.A.; Bracht, A.; Castoldi, R.; da Morais, R.G.; Baesso, M.L.; Peralta, R.A.; de Souza, C.G.M.; de Sa-Nakanishi, A.B.; Peralta, R.M. Inhibition of salivary and pancreatic α-amylases by a pinhao coat (Araucaria angustifolia) extract rich in condensed tannin. Food Res. Int., 2014, 56, 1-8.
[80]
Tadera, K.; Minami, Y.; Takamatsu, K.; Matsuoka, T. Inhibition of alpha-glucosidase and alpha-amylase by flavonoids. J. Nutr. Sci. Vitaminol. (Tokyo), 2006, 52(2), 149-153.
[81]
Tintu, I.; Dileep, K.V.; Augustine, A.; Sadasivan, C. An isoquinoline alkaloid, berberine, can inhibit fungal alpha amylase: enzyme kinetic and molecular modeling studies. Chem. Biol. Drug Des., 2012, 80(4), 554-560.
[82]
Yuan, E.; Liu, B.; Wei, Q.; Yang, J.; Chen, L.; Li, Q. Structure activity relationships of flavonoids as potent alpha-amylase inhibitors. Nat. Prod. Commun., 2014, 9(8), 1173-1176.
[83]
Yong, J.W.H.; Ge, L.; Ng, Y.F.; Tan, S.N. The chemical composition and biological properties of coconut (Cocos nucifera L.) water. Molecules, 2009, 14(12), 5144-5164.
[84]
Ngadi, N.; Halim, N.A.A.; Ibrahim, M.N.M. Isolation and characterization of vanillin from coconut husk lignin via alkaline nitrobenzene oxidation. Jurnal Teknologi, 2014, 67(4), 19-23.
[85]
Lee, J.H.; Hwang, H.; Moon, J.; Choi, J.W. Characterization of hydrothermal liquefaction products from coconut shell in the presence of selected transition metal chlorides. J. Anal. Appl. Pyrolysis, 2016, 122, 415-421.
[86]
Akpan, E.J.; Etim, O.E.; Akpan, H.D.; Usoh, I.F. Fatty acid profile and oil yield in six different varieties of fresh and dry samples of coconuts (Cocos nucifera). Pak. J. Nutr., 2006, 5(2), 106-109.
[87]
Kotarsky, K.; Nilsson, N.E.; Flodgren, E.; Owman, C.; Olde, B. A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs. Biochem. Biophys. Res. Commun., 2003, 301(2), 406-410.
[88]
Huang, C-H.; Chen, M-F.; Chung, H-H.; Cheng, J-T. Antihyperglycemic effect of syringaldehyde in streptozotocin-induced diabetic rats. J. Nat. Prod., 2012, 75(8), 1465-1468.
[89]
Mnafgui, K.; Kaanich, F.; Derbali, A.; Hamden, K.; Derbali, F.; Slama, S.; Allouche, N.; Elfeki, A. Inhibition of key enzymes related to diabetes and hypertension by Eugenol in vitro and in alloxan-induced diabetic rats. Arch. Physiol. Biochem., 2013, 119(5), 225-233.
[90]
Hashimoto, J.; Motohashi, K.; Sakamoto, K.; Hashimoto, S.; Yamanouchi, M.; Tanaka, H.; Takahashi, T.; Takagi, M.; Shin-ya, K. Screening and evaluation of new inhibitors of hepatic glucose production. J. Antibiot. (Tokyo), 2009, 62(11), 625-629.
[91]
Crowe, T.C.; Seligman, S.A.; Copeland, L. Inhibition of enzymic digestion of amylose by free fatty acids in vitro contributes to resistant starch formation. J. Nutr., 2000, 130(8), 2006-2008.
[92]
Lee, Y-C.; Chang, H-H.; Chiang, C-L.; Liu, C-H.; Yeh, J-I.; Chen, M-F.; Chen, P-Y.; Kuo, J-S.; Lee, T.J.F. Role of perivascular adipose tissue-derived methyl palmitate in vascular tone regulation and pathogenesis of hypertension. Circulation, 2011, 124(10), 1160-1171.
[93]
Schmidt, A.; Vogel, R.L.; Witherup, K.M.; Rutledge, S.J.; Pitzenberger, S.M.; Adam, M.; Rodan, G.A. Identification of fatty acid methyl ester as naturally occurring transcriptional regulators of the members of the peroxisome proliferator-activated receptor family. Lipids, 1996, 31(11), 1115-1124.
[94]
Balamurugan, R.; Duraipandiyan, V.; Ignacimuthu, S. Antidiabetic activity of γ-sitosterol isolated from Lippia nodiflora L. in streptozotocin induced diabetic rats. Eur. J. Pharmacol., 2011, 667(1-3), 410-418.
[95]
Latini, G.; Scoditti, E.; Verrotti, A.; De Felice, C.; Massaro, M. Peroxisome proliferator-activated receptors as mediators of phthalate-induced effects in the male and female reproductive tract: epidemiological and experimental evidence. PPAR Res., 2008, 2008359267.
[96]
Lau, C.; Abbott, B.D.; Corton, J.C.; Cunningham, M.L. PPARs and xenobiotic-induced adverse effects: relevance to human health. PPAR Res., 2010, 2010954639.
[97]
Judson, P.; Stalford, S.; Vessey, J. Assessing conifidence in predictions made by knowledge-based systems. Toxicol. Res., 2013, 2, 70-79.
[98]
Optibrium Ltd. Cambridge, United Kingdom. Available at: https://www.optibrium.com/ (Accessed January 1, 2016),
Related Journals
Current Diabetes Reviews
Current Medicinal Chemistry
Current Pharmaceutical Design
Current Topics in Medicinal Chemistry
Current Respiratory Medicine Reviews
Infectious Disorders - Drug Targets
Anti-Infective Agents
Coronaviruses
Recent Advances in Inflammation & Allergy Drug Discovery
Current Probiotics
Related Books
Mitochondrial DNA and the Immuno-inflammatory Response: New Frontiers to Control Specific Microbial Diseases
Pharmacological and Molecular Perspectives on Diabetes
Frontiers in Clinical Drug Research – Anti Allergy Agents
Frontiers in Clinical Drug Research-Diabetes and Obesity
Frontiers in Inflammation
Frontiers in Clinical Drug Research-Diabetes and Obesity
Article Metrics
37
4