Hepatoprotective studies of floral extracts of Gomphrena serrata L. and piperic acid on CCl4 induced hepatotoxicity

The present investigation aims to isolate, characterise and evaluate the phytoconstituents of Gomphrena serrata L. responsible for hepatoprotective activity in carbon tetrachloride-induced hepatotoxicity models both in vitro and in vivo . The plant species has not been explored for various therapeutic activities. HPLC analysis of subfraction of plant extract showed the presence of piperine, which was isolated and further hydrolysed to piperic acid. The results of the study indicate that the plant hydroalcoholic, acetone extracts at 500 mg/kg and compound piperic acid at 0.5 mg/kg exhibited better results in the regeneration of damaged hepatocytes and reduction of biochemical marker enzymes. The hepatoprotective activity might be due to inhibition of cytochrome P450 2E induced ER and oxidative stress. The present study reveals that the hepatoprotective activity of floral extracts might be due to in situ conversion of piperine into piperic acid. As piperic acid showed the equipotent potential to standard drug silymarin, it can be further developed as a hepatoprotective drug.

[1]  D. Ghosh,et al.  Acute and sub-acute (30-day) toxicity studies of Aegialitis rotundifolia Roxb., leaves extract in Wistar rats: safety assessment of a rare mangrove traditionally utilized as pain antidote , 2019, Clinical Phytoscience.

[2]  Abdul Rahaman Shaik,et al.  Hepatoprotective activity of 2-piperidone isolated from leaf extracts of Talinum portulacifolium ( Forssk . ) Asch . ex Schweinf in carbon tetrachloride induced hepatotoxicity , 2019 .

[3]  M. Jahangir,et al.  Antimicrobial, hemolytic and thrombolytic activities of some new N-substituted-2-({5-[(1E,3E)F-4-(1,3-benzodioxol- 5-yl)-1,3-butadienyl]-1,3,4-oxadiazol-2-yl}sulfanyl) propanamides , 2017 .

[4]  Dongjie Zhang,et al.  Antioxidant and hepatoprotective activity of kaempferol 3-O-β-d- (2,6-di-O-α-l-rhamnopyranosyl)galactopyronoside against carbon tetrachloride-induced liver injury in mice , 2017, Food Science and Biotechnology.

[5]  S. Munusamy,et al.  Structure–activity relationship of piperine and its synthetic amide analogs for therapeutic potential to prevent experimentally induced ER stress in vitro , 2017, Cell Stress and Chaperones.

[6]  Hussein Kamil Hamid,et al.  Extraction, isolation and characterization of Pyrrolizidine Alkaloids present in Senecio vulgaris Linn grown in Iraq , 2016 .

[7]  A. Rani,et al.  IN VITRO & IN VIVO ANTIASTHMATIC STUDIES ON THE FLORAL EXTRACTS OF GOMPHRENA SERRATA L. , 2016 .

[8]  K. V. Peter,et al.  Quality Assurance in Spices and Spice Products - Modern Methods of Analysis , 2015 .

[9]  C. Sadasivan,et al.  Derivatives Form Better Lipoxygenase Inhibitors than Piperine: In Vitro and In Silico Study , 2015, Chemical biology & drug design.

[10]  K. Takao,et al.  Synthesis and biological evaluation of piperic acid amides as free radical scavengers and α-glucosidase inhibitors. , 2015, Chemical & pharmaceutical bulletin.

[11]  A. Husain,et al.  Design, synthesis and biological evaluation of piperic acid triazolyl derivatives as potent anti-inflammatory agents. , 2015, European journal of medicinal chemistry.

[12]  Yanjiang Qiao,et al.  Synthesis and Antihyperlipidemic Activity of Piperic Acid Derivatives , 2015, Natural product communications.

[13]  S. Sharma Qualitative Determination of the Pyrrolizidine Alkaloids in Different Traditional Medicinal Plants , 2015 .

[14]  E. E. Oghenesuvwe Guidelines on Dosage Calculation and Stock Solution Preparation in Experimental Animals’ Studies , 2014 .

[15]  R. Khan,et al.  CCl4-induced hepatotoxicity: protective effect of rutin on p53, CYP2E1 and the antioxidative status in rat , 2012, BMC Complementary and Alternative Medicine.

[16]  S. Yoon,et al.  Piperine, a component of black pepper, inhibits adipogenesis by antagonizing PPARγ activity in 3T3-L1 cells. , 2012, Journal of agricultural and food chemistry.

[17]  R. Domitrović,et al.  Preventive and therapeutic effects of oleuropein against carbon tetrachloride-induced liver damage in mice. , 2012, Pharmacological research.

[18]  A. Petruczynik Analysis of alkaloids from different chemical groups by different liquid chromatography methods , 2012 .

[19]  K. Jeong,et al.  The roles of ER stress and P450 2E1 in CCl(4)-induced steatosis. , 2011, The international journal of biochemistry & cell biology.

[20]  A. Shuid,et al.  Acute and subacute toxicity studies of Eurycoma longifolia in male rats , 2011 .

[21]  F. Shahidi,et al.  Lipid oxidation and improving the oxidative stability. , 2010, Chemical Society reviews.

[22]  S. Reshmi,et al.  Isolation of piperdine from Piper nigrum and its antiproliferative activity , 2010 .

[23]  J. Schellberg,et al.  Characterization of phenotypic diversity, yield and response to drought stress in a collection of Rhodes grass (Chloris gayana Kunth) accessions , 2010 .

[24]  D. Banji,et al.  EXTRACTION, IDENTIFICATION, FORMULATION AND EVALUATION OF PIPERINE IN ALGINATE BEADS. , 2009 .

[25]  Hua Jiang,et al.  Protective effects of dehydrocavidine on carbon tetrachloride-induced acute hepatotoxicity in rats. , 2008, Journal of ethnopharmacology.

[26]  P. Muriel,et al.  Beneficial drugs for liver diseases , 2008, Journal of applied toxicology : JAT.

[27]  J. Harborne,et al.  Phytochemical Methods: A Guide to Modern Techniques of Plant Analysis. Second Edition , 1990, Brittonia.

[28]  S. Hasnain,et al.  Effect of different hormonal combinations on regeneration of callus of Gomphrena globosa L. , 2007, Pakistan journal of biological sciences : PJBS.

[29]  C. Lans,et al.  Ethnomedicines used in Trinidad and Tobago for urinary problems and diabetes mellitus , 2006, Journal of ethnobiology and ethnomedicine.

[30]  Y. Masuda [Learning toxicology from carbon tetrachloride-induced hepatotoxicity]. , 2006, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan.

[31]  C. Stancu,et al.  Statins: mechanism of action and effects , 2001, Journal of cellular and molecular medicine.

[32]  S. Sheweita,et al.  Carbon tetrachloride-induced changes in the activity of phase II drug-metabolizing enzyme in the liver of male rats: role of antioxidants. , 2001, Toxicology.

[33]  R. Zangar,et al.  Cytochrome P450 2E1 is the primary enzyme responsible for low-dose carbon tetrachloride metabolism in human liver microsomes. , 2000, Chemico-biological interactions.

[34]  OECD GUIDELINE FOR THE TESTING OF CHEMICALS Acute Oral Toxicity : Up-and-Down Procedure , 1998 .

[35]  Y. Bajaj Somatic Hybridization in Crop Improvement I , 1994, Biotechnology in Agriculture and Forestry.

[36]  J. Khan,et al.  Toxins in the seedlings of some varieties of grass pea (Lathyrus sativus). , 1993, Natural toxins.

[37]  E. Janzen,et al.  Oxygen- and carbon-centered free radical formation during carbon tetrachloride metabolism. Observation of lipid radicals in vivo and in vitro. , 1984, The Journal of biological chemistry.

[38]  D. Greenblatt,et al.  Kinetics of intravenous and intramuscular morphine. , 1979, Clinical pharmacology and therapeutics.

[39]  A. Bogdan,et al.  Tropical Pasture and Fodder Plants-Grasses and Legumes , 1977 .

[40]  J. Harborne Phytochemical Methods: A Guide to Modern Techniques of Plant Analysis , 1973 .

[41]  A. Chatterjee,et al.  Alkaloids of Piper longum Linn. I. Structure and synthesis of piperlongumine and piperlonguminine. , 1967, Tetrahedron.

[42]  R. Manske The Alkaloids: Chemistry and Physiology, Vol. VI , 1961 .