[Anti-inflammatory constituents, aloesin and aloemannan in Aloe species and effects of tanshinon VI in Salvia miltiorrhiza on heart].
Cinnamoyl, p-coumaroyl, feruloyl, caffeoyl aloesin, and related compounds were isolated from Aloe species. The antiinflammatory and antioxidative activities of these compounds were examined based on the structure-activity relationship. It was suggested that the bioactivities may link to acyl ester groups in aloesin, together with those of aloesin-related compounds. However, investigations using the contact hypersensitivity response indicated a preventive effect of aloesin on the UV-B-induced immune suppression. Furthermore, aloesin inhibited tyrosine hydroxylase and dihydroxyphenylalanine (DOPA) oxidase activities of tyrosinase from normal human melanocyte cell lysates. These results show that aloesin prevents not only UV-B-induced immune suppression, but also could be a positive pigment-altering agent for cosmetic application. In preclinical study, aloe extract was investigated using phagocytosis and nitroblue tetrazolium chloride (NBT) reduction in adult bronchial asthma, and high molecular-weight materials, such as polysaccharide and glycoprotein fractions, were identified as active ingredients. The neutral polysaccharides, aloemannan and acemannan showed antitumor, antiinflammatory and immunosuppressive activities, and glycoprotein fractions with bradykinindegrading and cell proliferation-stimulating activities were identified from the nondialysate fraction of the gel part of Aloe species. Verectin fractionated from Aloe vera gel was examined biochemically and immunochemically, and verectin antibody was used in the appraisal of commercial Aloe vera gel products. It was reported that aloesin stimulates the proliferation of cultured human hepatoma SK-Hep 1 cells. Thus aloesin, related compounds, and high molecular-weight materials, such as aloemannan and verectin, may act in concert to exert therapeutic properties for wounds, burns and inflammation. The biodisposition of fluoresceinylisothiocyanate (FITC)--labeled aloemannan (FITC-AM) with the homogenate from some organs in mice was demonstrated, and FITC-AM was metabolized to a smaller molecule (MW 3000) by the large intestinal microflora in feces. The modified aloe polysaccharide (MW: 80000) with cellulase under restricted conditions, immunologically stimulated the recovery of UV-B-induced tissue in jury. Thus the modified polysaccharides of aloemannan, together with acemannan (MW: about 600000), are expected to participate in biological activity following oral administration. The effects of tanshinone VI, a diterpenoid isolated from Salvia miltiorrhiza, on the heart are reviewed. First, the effects on the posthypoxic recovery of contractile function of perfused rat hearts were examined. Hypoxia/reoxygenation induced a release of purine nucleosides and bases (ATP metabolites) and resulted in little recovery of contractile force of reoxygenated hearts. Pretreatment of the perfused heart with 42 nM tanshinone VI under hypoxic conditions attenuated the release of ATP metabolites during hypoxia/reoxygenation. Treatment with tanshinone VI enhanced the posthypoxic recovery of myocardial contractility. These results show that tanshinone VI may protect the heart against hypoxia/reoxygenation injury and improve the posthypoxic cardiac function. Second, the effects of tanshinone VI on in vitro myocardial remodeling were examined. Cardiomyocytes and cardiac fibroblasts were isolated from neonatal rat hearts, and simultaneously prepared insulin-like growth factor-1 (IGF-1) induced the hypertrophy of cardiomyocytes. IGF-1 increased the collagen synthesis of cardiac fibroblasts, that is, in vitro fibrosis. The hypertrophy of cardiomyocytes was attenuated in the presence of tanshinone VI in the culture medium. The fibrosis of cardiac fibroblasts was decreased by treatment with tanshinone VI. When tanshinone VI was added to cardiac fibroblast-conditioned medium, the medium-mediated hypertrophy of cardiomyocytes was also attenuated. These results show that tanshinone VI may attenuate in vitro cardiac remodeling. The series of studies has shown that tanshinone VI protects the myocardium against hypoxia/reoxygenation injury and attenuates progression of in vitro myocardial remodeling, suggesting that tanshinone VI is a possible agent for the treatment of cardiac disease with contractile failure.
Yagi
Akira
A
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 985 Gakuen-cho, Fukuyama 729-0292, Japan. yagi@fupharm.fukuyama-u.ac.jp
Takeo
Satoshi
S
D000504:Aloe / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents; D002867:Chromones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D016166:Free Radical Scavengers; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008351:Mannans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D010616:Phenanthrenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D020257:Ventricular Remodeling / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D002867:Chromones; D016166:Free Radical Scavengers; D005960:Glucosides; D008351:Mannans; D010616:Phenanthrenes; C120643:aloemannan; C090979:tanshinone VI; C069868:aloesin