Hepatoprotective Effect of Baicalin, a Major Flavone from<i>Scutellaria radix</i>, on Acetaminophen‐Induced Liver Injury in Mice

Jang, Seon Il; Kim, H. J.; Hwang, Kwontaek; Jekal, Seung-Joo; Pae, Hyun‐Ock; Choi, B. M.; Yong-Gab, Yun; Kwon, Tae-Oh; Chung, Hui-Wen; Kim, Y. C.

doi:10.1081/iph-120026443

Cited by 71 publications

(28 citation statements)

References 14 publications

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“…For instance, the suppressive effects of glycosidic flavone and flavonols from green tea on GalN-induced liver injury (33), baicaline on APAP- (47) or GalN/LPSinduced liver injury (48), glycosidic flavone from rice on carbon tetrachloride-induced liver injury (49), hesperidin on LPS-induced liver injury (50), and methoxy flavone and luteoline from Cleome droserifolia on carbon tetrachloride-induced liver injury (51) have been shown. These previous studies appear to support the concept that certain types of flavonoids might exhibit hepatoprotective effects regardless of the type of liver injury.…”

Section: Discussionmentioning

confidence: 99%

Hepatoprotective Effects of Flavonoids from Shekwasha (Citrus depressa) against D-Galactosamine-Induced Liver Injury in Rats

Akachi

Shiina

Ohishi

et al. 2010

J Nutr Sci Vitaminol

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SummaryWe attempted to isolate the constituent(s) responsible for the suppressive effect of the juice of shekwasha, a citrus produced in Okinawa Prefecture, on D -galactosamine (GalN)-induced liver injury in rats. Liver injury-suppressive activity, as assessed by plasma alanine aminotransferase and aspartate aminotransferase activities, was found only in the fraction that was extracted with n -hexane when three fractions were added to the diet and fed to rats. Of five compounds isolated from the n -hexane-soluble fraction by silica gel column chromatography, three compounds had liver injury-suppressive effects when five compounds were singly force-fed to rats at a level of 300 mg/kg body wt 4 h before the injection with GalN. The structures of the three active compounds were determined as 3 ′ ,4 ′ ,5,6,7,8-hexamethoxyflavanone (citromitin), 4 ′ ,5,6,7,8-pentamethoxyflavone (tangeretin) and 3 ′ ,4 ′ ,5,6,7,8-hexamethoxyflavone (nobiletin), which are known flavonoids mainly existing in citrus. Nobiletin, the most important compound in the n -hexane-soluble fraction, also had suppressive effects on liver injuries induced by carbon tetrachloride, acetaminophen and GalN/lipopolysaccharide (LPS) in addition to liver injury induced GalN. Nobiletin suppressed GalN/LPS-induced increases in plasma tumor necrosis factor (TNF)-␣ and nitric oxide (NO) concentrations and hepatic mRNA levels for inducible NO synthase and DNA fragmentation. These results suggest that nobiletin suppressed GalN/LPS-induced liver injury at least by suppressing the production of both TNF-␣ and NO. The results obtained here indicate that the hepatoprotective effect of shekwasha juice is mainly ascribed to several polymethoxy flavonoids included in the juice. Key Words D -galactosamine, liver injury, shekwasha, Citrus depressa , flavonoids Fruits and vegetables are important as sources of several nutrients such as vitamins, minerals and dietary fibers. Fruits and vegetables also contain a variety of constituents, which are characteristic of the species of plant. It is widely recognized that relatively high intakes of fruits and vegetables are desirable for prevention of diseases and maintenance of healthy conditions ( 1 ). Previously we reported that several kinds of fruit had suppressive effects on D -galactosamine (GalN)-induced liver injury in rats when various kinds of lyophilized fruit were added to the diet ( 2 ). Furthermore, recently we found that some fruit juices, e.g., camu-camu and shekwasha, also had suppressive effects on GalNinduced liver injury in rats, and we identified the active compound (unpublished data). These findings indicate that certain fruits (and possibly vegetables) have a hepatoprotective effect in addition to nutritional effects.Since the liver is the central organ of many types of metabolism, the hepatoprotective effect of foods is worthwhile to investigate in detail, not only from the viewpoint of food science but also from the viewpoint of nutrition.In the present study, we attempted to isolate the constituent(s) res...

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Section: Discussionmentioning

confidence: 99%

Hepatoprotective Effects of Flavonoids from Shekwasha (Citrus depressa) against D-Galactosamine-Induced Liver Injury in Rats

Akachi

Shiina

Ohishi

et al. 2010

J Nutr Sci Vitaminol

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“…Compared to other isoforms, CYP2E1 is usually relevant to only minor metabolic reactions of certain drugs (10). Interestingly, oral administration of high doses of the flavones wogonin, bacalein, or the baicalein glucuronide baicalin from Scutellaria radix decreased hepatic protein expression and enzyme activity of CYP2E1 in mice (10,11).…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Kaempferol on Isoniazid- and Rifampicin-Induced Hepatotoxicity

Shih

Young

Lee

et al. 2013

AAPS J

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Abstract. Isoniazid (INH) and rifampicin (RIF) are the first-line drugs for antituberculosis (anti-TB) chemotherapy. The levels of serum transaminases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] are abnormal in 27% of patients undergoing INH and RIF treatments and in 19% of patients undergoing treatment with INH alone. Cytochrome P450 2E1 (CYP2E1) metabolizes many toxic substrates, including ethanol, carbon tetrachloride, and INH, which ultimately results in liver injury. The objective of this study was to screen for CYP2E1 inhibitors in vitro and investigate whether the selected compound could prevent INH/RIF-induced hepatotoxicity in vivo. We screened 83 known compounds from food and herbal medicines as inhibitors of CYP2E1. The hepatotoxic dose of INH/RIF was 50/100 mg kg −1 day −1 . Hepatotoxicity was assessed using galactose single-point (GSP) method (a quantitative measurement of liver function), histopathological examination of the liver, malondialdehyde (MDA) assay, and measurement of AST and ALT activities. Kaempferol inhibited CYP2E1 activity in mice by 0.31-to 0.48-fold (p<0.005). Mice with INH/RIF-induced hepatotoxicity showed significantly abnormal serum levels of AST and ALT, and GSP value, and these values could be decreased by the administration of kaempferol (p<0.005). Kaempferol significantly reduced the depletion of hepatic glutathione and prevented the increase in MDA formation in mice. Furthermore, kaempferol did not affect the anti-TB effects of INH/RIF. To our knowledge, this is the first report of kaempferol's utility as an adjuvant for preventing CYP2E1-mediated hepatotoxicity induced by drugs such as INH and RIF.

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“…These constituents exhibit anti-inflammatory, antiallergic, anti-oxidant, and hepatoprotective, and antitumor effects (Chou et al, 2003;Jang et al, 2003;Lim, 2003;Kim et al, 2005). These components are poorly absorbed from the gastrointestinal tract in its native form due to their hydrophilic properties and must be hydrolyzed by intestinal microflora in the intestine to their aglycones in human and rats (Akao et al, 2000;Yim et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Metabolism of Wogonoside by Human Fecal Microflora and Its Anti-pruritic Effect

Trinh¹,

Jang²,

Han³

et al. 2009

Biomolecules and Therapeutics

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-To understand the relationship between the metabolism of wogonoside from the rhizome of Scutellaria baicalensis, and its anti-pruritic effect, we anaerobically incubated it with human fecal microflora, identified its metabolite identified, and investigated its anti-pruritic effect in compound 48/80 or histamineinduced pruritic mice. Wogonoside was metabolized to wogonin, with metabolic activity of 6.9 ± 5.1 nmol/h/ mg wet weight of fecal microflora. Orally administered wogonoside had more potent anti-scratching behavioral effect in compound 48/80 or histamine-treated mice than intraperitoneally treated one, apart from orally administered its metabolite, wogonin, which was more potent than the orally administered one. Wogonoside showed more potent anti-pruritic effects when administered at 5 h prior to the pruritic agent treatment than when administered at 1 h before. However, wogonin orally administered 1 h before the treatment with pruritic agents showed a more potent anti-pruritic effect than when treated at 5 h before. Orally administered wogonoside may be metabolized to wogonin in the intestine and its anti-scratching behavioral effect may be dependent on its metabolism by intestinal microflora.

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Hepatoprotective Effect of Baicalin, a Major Flavone fromScutellaria radix, on Acetaminophen‐Induced Liver Injury in Mice

Cited by 71 publications

References 14 publications

Hepatoprotective Effects of Flavonoids from Shekwasha (Citrus depressa) against D-Galactosamine-Induced Liver Injury in Rats

Hepatoprotective Effects of Flavonoids from Shekwasha (Citrus depressa) against D-Galactosamine-Induced Liver Injury in Rats

Protective Effects of Kaempferol on Isoniazid- and Rifampicin-Induced Hepatotoxicity

Metabolism of Wogonoside by Human Fecal Microflora and Its Anti-pruritic Effect

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