title: Evaluation of anti-hypertensive activity of Ulmus wallichiana extract and fraction in SHR, DOCA-salt- and L-NAME-induced hypertensive rats.
abstract: BACKGROUND
  Ulmus wallichiana Planchon (Himalayan Elm), a traditional medicinal plant, used in fracture healing in folk tradition of Uttarakhand, Himalaya, India. It is also used as diuretic. U. rhynchophylla, native to China, known as Gou Teng in Chinese medicine, is used for hypertension (WHO). U. macrocarpa has antihypertensive and vasorelaxant activity. However, no detailed studies related to hypertension have been reported previously, so we have explored the antihypertensive activity of U. wallichiana.
  
  
  OBJECTIVE
  To investigate the pharmacological effect of ethanolic extract (EE) and butanolic fraction (BF) of U. wallichiana in hypertensive rats.
  
  
  METHODS
  SHR, DOCA-salt- and L-NAME-induced hypertension models were used. Treatment was performed by oral administration of EE and BF of U. wallichiana (500mg/kg/day and 50mg/kg/day) for 14 days. Then blood pressure was measured by non-invasive blood pressure (NIBP) measurement technique. Invasive blood pressure (IBP) was also reported to support the NIBP data. Concentrations of plasma renin, angiotensin II (Ang II), nitrate/nitrite (NO), cGMP were estimated. Angiotensin-converting enzyme (ACE) activity and ROS activity were also estimated.
  
  
  RESULTS
  Blood pressure was significantly higher in SHR as compared to normotensive wistar group (170.59±0.83mmHg vs 121.54±1.24mmHg, respectively). SBP was increased in DOCA-salt induced group compared to their control (132.77±3.90mmHg vs 107.85±5.95mmHg, respectively) and L-NAME-induced group compared to their control (168.55±5.07mmHg vs 113.03±4.13mmHg, respectively). The treatment of extract and fraction of U. wallichiana significantly decreased the blood pressure in SHR+EE (151.26±1.85mmHg, p<0.001), SHR+BF (140.44±1.16mmHg, p<0.001); DOCA+EE (113.43±5.44mmHg, p<0.05), DOCA+BF (105.09±5.12mmHg, p<0.05) and L-NAME+EE (119.76±4.39mmHg, p<0.001), L-NAME+BF (117.50±7.27mmHg, p<0.001) compared to their respective diseased control groups. The plasma renin, Ang II and ACE activity were also significantly decreased and augmented the NO and cGMP levels. It also down regulated the expression of Renin, ACE, NOS3 and TGF-β1 at mRNA levels.
  
  
  CONCLUSIONS
  The EE and BF probably reducing the BP via Renin-angiotensin-aldosterone system and NO/cGMP signaling pathway. The decrease in blood pressure may be due to presence of quercetin analogue flavonoids (2S,3S)-(+)-3',4',5,7-tetrahydroxydihydroflavonol-6-C-β-D-glucopyranoside; 6-Glucopyranosyl-3,3',4',5,7-pentahydroxyflavone; 6-Glucopyranosyl-4',5,7-trihydroxyflavanone and (2S,3S)-(+)-4',5,7-trihydroxydihydroflavonol-6-C-β-D-glucopyranoside, may be due to its antioxidant activity. Thus EE and BF of U. wallichiana found to have the potential ability to be used as herbal medicament to treat hypertension.
authors.affiliation: Division of Pharmacokinetics & Metabolism, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow 226031, India.
authors.forename: Anees A
authors.initials: AA
authors.lastname: Syed
authors.affiliation: Division of Pharmacokinetics & Metabolism, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow 226031, India.
authors.forename: Shibani
authors.initials: S
authors.lastname: Lahiri
authors.affiliation: Division of Pharmacology, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow 226031, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Mohan
authors.affiliation: Division of Pharmacokinetics & Metabolism, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors.forename: Guru R
authors.initials: GR
authors.lastname: Valicherla
authors.affiliation: Division of Pharmacokinetics & Metabolism, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow 226031, India.
authors.forename: Anand P
authors.initials: AP
authors.lastname: Gupta
authors.affiliation: Division of Pharmacokinetics & Metabolism, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow 226031, India.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Riyazuddin
authors.affiliation: Division of Medicinal & Process Chemistry, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow 226031, India.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Division of Medicinal & Process Chemistry, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Maurya
authors.affiliation: Division of Pharmacology, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India. Electronic address: k_hanif@cdri.res.in.
authors.forename: Kashif
authors.initials: K
authors.lastname: Hanif
authors.affiliation: Division of Pharmacokinetics & Metabolism, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India. Electronic address: jr.gayen@cdri.res.in.
authors.forename: Jiaur R
authors.initials: JR
authors.lastname: Gayen
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects; D064791:Desoxycorticosterone Acetate / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D007194:India; D008297:Male; D008519:Medicine, Traditional; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000302:isolation & purification / Q000627:therapeutic use* / Q000633:toxicity; D018547:Plant Stems / Q000737:chemistry; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D023382:Toxicity Tests, Acute; D034403:Ulmus / Q000737:chemistry*
chemical_list: D000959:Antihypertensive Agents; D010936:Plant Extracts; D064791:Desoxycorticosterone Acetate; D019331:NG-Nitroarginine Methyl Ester
keywords: Blood pressure; DOCA; Hypertension; L-NAME; SHR; Ulmus wallichiana