Hepatoprotective Effect of Apocynum venetum and its Active Constituents

Abstract

The leaves of Apocynum venetum L. are used as a tea material in north China and Japan. A water extract (500 mg/kg/day, one week administration) of the leaves of A. venetum showed protective effects against carbon tetrachloride (CCl4, 30 microliters/mouse) or D-galactosamine (D-GalN, 700 mg/kg)/lipopolysaccharide (LPS, 20 micrograms/kg)-induced liver injury in mice. Tumor necrosis factor-alpha (TNF-alpha) secreted from LPS-stimulated macrophages is the most crucial mediator in the D-GalN/LPS-induced liver injury model. The extract had no significant inhibition on the increase of serum TNF-alpha (1169 +/- 132 pg/ml vs. 1595 +/- 314 pg/ml of control), but exhibited a complete inhibition at the concentration of 100 micrograms/ml on TNF-alpha (100 ng/ml)-induced cell death in D-GalN (0.5 mM)-sensitized mouse hepatocytes. Further activity-guided fractionation resulted in the isolation of fifteen flavonoids viz. (-)-epicatechin (1), (-)-epigallocatechin (2), isoquercetin (3), hyperin (4), (+)-catechin (5), (+)-gallocatechin (6), kaempferol-6'-O-acetate (7), isoquercetin-6'-O-acetate (8), catechin-[8,7-e]-4 alpha-(3,4-dihydroxpyhenyl)-dihydro-2(3H)-pyranone (9), apocynin B (10), apocynin A (11), cinchonain Ia (12), apocynin C (13), apocynin D (14) and quercetin (15). All the compounds showed inhibitory effects on TNF-alpha-induced cell death with different intensities. The flavonol glycosides 3, 4, 7 and 8 and the phenylpropanoid-substituted flavan-3-ols 11 and 12 showed potent inhibitory effects on TNF-alpha-induced cell death with IC50 values of 37.5, 14.5, 31.2, 55.1, 71.9 and 41.2 microM, respectively. In contrast, the clinically used 5 and its analogues 1, 2 and 6 showed apparent activity only at 80 microM. These flavonoids appeared to be the hepatoprotective principles of the leaves of A. venetum. The hepatoprotective effects exhibited by the extract and its constituents suggest a validation of the leaves as a tea material.

Effect of Oenanthe javanica flavone on human and duck hepatitis B virus infection

“…Similar results of the inhibitory effect of Oj extracts on HBsAg and HBeAg production in cultured 2.2.15 cells was also observed [19] . However, what the active part of Oj against HBV is is still unknown.…”

“…Histopathological examination also confirmed the function of OjF protecting the liver in DHBV-infected ducklings. Xiong Q et al [19] reported that Apocynum ventun extracts containing hyperoside and quercetin had hepatoprotective activity, and OjF contained these two compounds. These results demonstrated the antihepatitis B virus effect of OjF, which were consistent with antiviral activity of Oj [7,8] , making OjF a candidate for future evaluation in patients with HBV infection.…”

In vivo and in vitro antiviral activity of hyperoside extracted from Abelmoschus manihot (L) medik

“…Therefore, further investigation of the DNA polymerase level in HBV replication is required. Xiong et al [18] used the in vitro D-GalN/TNF-α model to confirm that many flavonoids, including hyperoside, protect liver cells from TNF-α-induced hepatocyte apoptosis. TNF-α has been found to be a very important pathogenic mediator in patients with alcoholic liver disease and viral hepatitis, as well as in many animal liver injury models [27] .…”

“…Hyperoside (hyperin), quercetin-3-O-β-D-galactoside, is a flavonol glycoside which widely exists in many traditional medicines, such as Semen cuscutae [4] , St John's wort [5,6] , hawthorn [7] , Balbisia calycina [8] , and Alchornea cordifolia [9] . As an important bioactive compound, hyperoside has been documented to possess antiviral activity [10,11] , antinociceptive [12][13][14] , anti-inflammatory [15] , cardioprotective [7,16,17] , hepatoprotective [18][19][20] , and gastricmucosal-protective effects [21,22] . In previous studies, it has been shown that hyperoside demonstrates hepatoprotective properties in various chemically-induced hepatocyte injury models [18][19][20] .…”

“…As an important bioactive compound, hyperoside has been documented to possess antiviral activity [10,11] , antinociceptive [12][13][14] , anti-inflammatory [15] , cardioprotective [7,16,17] , hepatoprotective [18][19][20] , and gastricmucosal-protective effects [21,22] . In previous studies, it has been shown that hyperoside demonstrates hepatoprotective properties in various chemically-induced hepatocyte injury models [18][19][20] . However, to our knowledge, the activity of hyperoside against viral hepatitis has never been tested.…”