title: The cardioprotective effects of marrubiin, a diterpenoid found in Leonotis leonurus extracts.
abstract: BACKGROUND
  Leonotis leonurus L. (Lamiaceae) is used as a traditional medicine for a variety of ailments in South Africa. The diterpene marrubiin is the major product constituent in specimens of this plant occurring in South Africa.
  
  
  METHODS
  Marrubiin isolated from South African specimens of L. leonurus in addition to an organic extract of L. leonurus were tested in vivo, ex vivo and in vitro for their anticoagulant, antiplatelet and anti-inflammatory activities.
  
  
  RESULTS
  Marrubiin and the organic extract suppressed coagulation, platelet aggregation and inflammatory markers. For the coagulation markers it was found that the organic extract and marrubiin significantly prolonged activated partial thromboplastin time (APTT). Fibrin and D-dimer formation were drastically decreased. These findings were observed in an ex vivo model and an obese rat model. Chemokines enhance leukocyte recruitment to inflammatory sites. TNF-α and RANTES secretion were significantly reduced by the extract and marrubiin when determined in the obese rat model relative to the controls. Calcium mobilization and TXB(2) synthesis were suppressed by the extract and marrubiin. An in vitro model was used to elucidate the antiplatelet mechanism and it was found that the extract and marrubiin inhibited platelet aggregation by inhibiting the binding of fibrinogen to glycoprotein (GP) IIb/IIIa receptor in a concentration dependent manner.
  
  
  CONCLUSIONS
  The findings reflect that marrubiin largely contributes to the extract's anticoagulant, antiplatelet and anti-inflammatory effects observed.
authors: Department of Biochemistry and Microbiology, Nelson Mandela Metropolitan University, PO Box 77000, Port Elizabeth, 6031 South Africa.
authors: Nandipha
authors: N
authors: Mnonopi
authors: Ruby-Ann
authors: RA
authors: Levendal
authors: Michael T
authors: MT
authors: Davies-Coleman
authors: Carminita L
authors: CL
authors: Frost
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D000925:Anticoagulants / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005337:Fibrin / Q000096:biosynthesis; D005338:Fibrin Fibrinogen Degradation Products / Q000096:biosynthesis; D005340:Fibrinogen / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D006023:Glycoproteins / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D019686:Lamiaceae / Q000737:chemistry*; D008297:Male; D009765:Obesity / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D010314:Partial Thromboplastin Time; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013931:Thromboxanes / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; D018946:Chemokine CCL5; D004224:Diterpenes; D005338:Fibrin Fibrinogen Degradation Products; D005343:Fibrinolytic Agents; D006023:Glycoproteins; D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; D013931:Thromboxanes; D014409:Tumor Necrosis Factor-alpha; C036309:fibrin fragment D; D005337:Fibrin; D005340:Fibrinogen; C105731:marrubiin; D002118:Calcium