Microbial transformation and bioactivation of isoflavones from <Emphasis Type="Italic">Pueraria</Emphasis> flowers by human intestinal bacterial strains

The flowers from Pueraria, which are called Puerariae Flos, have been used since ancient times for recovery from alcohol intoxication. We elucidated the microbial transformation of the main isoflavones (1, 1a and 2) by using 29 commercially available human intestinal bacterial strains together with the bioactivation of the hepatoprotective activity of their metabolites. Tectoridin (1a), which contains only one glucosyl moiety, was metabolized to its aglycone 1b by various bacterial strains. On the other hand, the metabolism of 1 and 2, which both have disaccharide groups, was limited to specific bacterial strains. The metabolites 1c and 2c obtained from the Peptostreptococcus productus strain were completely different from those produced by the other strains. These metabolites were identified as 6-hydroxygenistein and 6-hydroxybiochanin A, respectively. The glycosides 1, 1a and 2 did not show any hepatoprotective activity, whereas aglycones 1b and 2b showed moderate activity. Furthermore, the hepatoprotective activity of the demethylated metabolites 1c and 2c was extremely potent. Although not all people have P. productus in their gastrointestinal tract, the O-demethylated compounds might become one of the bioactivated metabolites when Puerariae Flos is administered orally.     

Hepatoprotective properties of red betel (Piper crocatum Ruiz and Pav) leaves extract towards H2O2-induced HepG2 cells via anti-inflammatory,antinecrotic, antioxidant potency

BackgroundProlonged exposure of free radicals, or known as reactive oxygen species (ROS), in hepatic cells may cause oxidative stress. Without proper treatment, it can induce liver injury and fatal hepatic disease, including cirrhosis. Red betel (Piper crocatum Ruiz and Pav) is one of Indonesia’s medicinal plants that has been known to exhibit antioxidant, anti-inflammatory activities. This study aims to determine hepatoprotective effect of red betel leaves extract (RBLE) towards liver injury.MethodHydrogen peroxide-induced HepG2 cells were used as liver injury model·H₂O₂-induced HepG2 cells were treated with 25 µg/mL and 100 µg/mL RBLE. Several parameters were observed, including TNF-α level through ELISA; necrotic, apoptotic, dead, live cells; and ROS level through flow cytometry analysis; and GPX gene expression through qPCR.ResultThe study showed that treatment with RBLE were able to decrease TNF-α level; necrotic and death cells percentage; as well as ROS level. On the other hand, it were able to increase apoptotic and live cells percentage; as well as GPX gene expression. Low concentration (25 µg/mL) of RBLE treatment exhibited stronger anti-inflammatory activity as it was resulted in the lower TNF-α level and were able to switched hepatic cell death pathway from necrosis to apoptosis as shown by the shifted of apoptotic cells and necrotic cells percentage. This lead to lower death cells and ultimately improve live cells percentage. Meanwhile high concentration of RBLE (100 µg/mL) exhibited stronger antioxidant properties as indicated by lower ROS level and higher GPX gene expression.ConclusionOverall, this study was able to demonstrate hepatoprotective effect of RBLE towards liver injury model through its anti-inflammatory and antioxidant activities.     

保肝药在预防与治疗抗结核药所致肝损伤中的利用分析

目的：了解保肝药在预防与治疗抗结核药所致的肝损伤中的应用现状及趋势。方法：对我院2005-2009年在预防和治疗抗结核药引起的肝损伤中应用的保肝药的品种、用药数量、销售金额、用药频度（DDDS）、日均费用（DDC）等进行统计、分析。结果：我院所应用的保肝药涉及24个品种,5年间销售金额增长了280％,总DDDs增长了195％;注射用还原型谷胱甘肽、硫普罗宁注射液连续5年进入销售金额的前3名;葡醛内酯片的DDDs连续5年排第1位,注射用还原型谷胱甘肽的DDDs增加了265％,中成药的DDDs增长了259％。结论：保肝药在预防和治疗抗结核药引起的肝损伤中的应用呈明显的上升趋势。     

The hepatoprotective effect and chemical constituents of total iridoids and xanthones extracted from Swertia mussotii Franch

Ethnopharmacological relevance

Total iridoids and xanthones (TIXS) were extracted from Swertia mussotii Franch, one of the most important eight Tibetan medicines in China, which was recorded in the book of Jingzhu Bencao and used for clinical treatment of cholestatic hepatitis for many years. Our aim was to study the hepatoprotective effect and chemical constituents of the TIXS.

Materials and methods

Crude extracts were prepared using 90% ethanol, and individual fractions were collected following HPD-300 macroporous resin column chromatography. HPLC/MS was applied to qualitatively and quantitatively analyze the TIXS. Then, the alpha-naphthylisot hiocyanate-induced liver damage model was used to assess the hepatoprotective effect of the TIXS.

Results

A total of 12 compounds were identified by the fingerprint chromatography of the TIXS, and swertiamarin and swertianolin were shown to be its two main components. Oral administration of the TIXS at a dose of 35, 70 or 140 mg kg⁻¹, swertiamarin at a dose of 20 mg kg⁻¹ or swertianolin at a dose of 20 mg kg⁻¹, for 7 days in mice significantly reduced the alpha-naphthylisot hiocyanate-induced levels of alanine aminotransferase, aspartate aminotransferase and the total and direct bilirubins, and increased the bile flow (P<0.01).

Conclusion

These findings suggest that the TIXS exhibits significant hepatoprotective effect in the liver damage model induced by alpha-naphthylisot hiocyanate. Its active constituents include swertiamarin and swertianolin.     

The therapeutic effects of Portulaca oleracea L. in hepatogastric disorders

Aim

This research was conducted to obtain accurate information on the protective effects of Portulaca oleracea L. against hepatogastric diseases.

Synergistic effect of ursolic acid and piperine in CCl4 induced hepatotoxicity

BackgroundUrsolic acid (UA) is a potent plant-based hepatoprotective agent having poor bioavailability, which hampers its therapeutic efficacy. The present study tries to overcome this limitation by combining it with piperine (PIP), a proven bioenhancer and hepatoprotective agent.MethodsThe type of interaction (synergism, addition, or antagonism) resulting between UA and PIP was analyzed and quantified by isobologram and combination index analysis. The hepatoprotective activity of UA and PIP was evaluated by measuring the level of hepatic marker enzymes. Pharmacokinetic analysis was carried out to ascertain the improvement of bioavailability.ResultsThe combinations significantly decrease the enzyme levels, which indicate better hepatoprotective activity compared to single drugs. The relative oral bioavailability of UA was increased about tenfold (from AUC_0–t =12.78 ± 2.59 µg/h/ml to 125.15 ± 1.84 µg/h/ml) along with the improvement of plasma concentration and elimination half-life.ConclusionsThe findings indicated that the combination of PIP and UA is an effective strategy in enhancing the bioavailability and hepatoprotective potential of UA.

KEY MESSAGES

• Ursolic acid in a combination with piperine provides a synergistic hepatoprotective effect in carbon tetrachloride induced liver damage in rats.
• Piperine improves the pharmacokinetic properties of ursolic acid when given in combination.
• Piperine improves the relative oral bioavailability of ursolic acid by tenfold when combined together.

     

Luffa echinata Roxb.-A review on its ethanomedicinal,phytochemical and pharmacological perspective

Luffa echinata Roxb. (Cucurbitaceae) is a spreading climbing herb of tremendous medicinal importance, distributed throughout Pakistan, India, Bangladesh and Northern Tropical Africa. Traditionally various parts of the plant are being used for the treatment of different ailments such as jaundice, intestinal colic, enlargement of liver and spleen, leprosy, diabetes, bronchitis, nephritis, rheumatism, cirrhosis, dropsy, anthelmintic, stomach ache, snake bite, dog bite, fever, diarrohea and hemorrhoid disorder. The plant also possesses antioxidant, analgesic, anti-inflammatory, antidepressant, anxiolytic, antiepileptic, hepatoprotective, antibacterial, antifungal, antiulcer and anticancer activity. Research has been carried out using different techniques to support most of these claims. This review is an attempt to compile an up-to-date data on its ethanomedicinal, phytochemical and pharmacological perspective.     

Evaluation of the hepatoprotective effect of combination between hinokiflavone and Glycyrrhizin against CCl4 induced toxicity in rats

Liver diseases are one of the fatal syndromes due to the vital role of the liver. Most of the effective treatment of liver conditions are of natural origin. Silymarin (SI) is the standard drug used for treatment of impaired liver functions. Two natural compounds possessing promising liver protection and with different chemical structures namely; the bioflavonoid hinokiflavone (HF) isolated from Junipers phoenicea family Cupressaceae and the sweet saponin Glycyrrhizin (GL) present in Glycyrrhiza glabra (liquorice) were selected for the current study. Since the two compounds are of different nature, they may act by different mechanisms and express synergistic effect. Combination of the two compounds using to dose levels were challenged with single doses of HF, GL and SI as well. The comparison was monitored via measuring serum biochemical parameters including, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltranspeptidase (GGT), alkaline phosphatase (ALP) and total bilirubin, tissue parameters such as MDA, NP-SH and TP, histopathological study using light and electron microscope. Protective effect on kidney was also monitored histopathologically and biochemically through observing the levels of LDH, creatinine, creatinine-kinase, urea and uric acid. The combinations of HF and GL showed protective effect more than the used single doses of HF and GL alone. However, SI was superior to the used combination in the two used doses in all the measured parameters. The liver and kidney cells appearance under normal and electron microscope showed that SI treated groups showed almost normal cells with slight toxic signs. Cells from group treated with the higher doses of the combination of HF and GL showed slight signs of intoxication under light and electron microscope indicating good level of protection. Although the combination of HF and GL expressed good protection in the higher dose, however, the combination did not exceed the protective effect of SI.     

Baicalin provides protection against fluoxetine-induced hepatotoxicity by modulation of oxidative stress and inflammation

BACKGROUNDFluoxetine is one of the most widely prescribed anti-depressant drugs belonging to the category of selective serotonin reuptake inhibitors. Long-term fluoxetine treatment results in hepatotoxicity. Baicalin, a natural compound obtained from the Chinese herb Scutellaria baicalensis is known to have antioxidant, hepatoprotective and anti-inflammatory effects. However, the beneficial effects of baicalin against fluoxetine-induced hepatic damage have not previously been reported.AIMTo evaluate the protective action of baicalin in fluoxetine-induced liver toxicity and inflammation.METHODSMale albino Wistar rats were divided into seven groups. Group 1 was the normal control. Oral fluoxetine was administered at 10 mg/kg body weight to groups 2, 3, 4 and 5. In addition, groups 3 and 4 were also co-administered oral baicalin (50 mg/kg and 100 mg/kg, respectively) while group 5 received silymarin (100 mg/kg), a standard hepatoprotective compound for comparison. Groups 6 and 7 were used as a positive control for baicalin (100 mg/kg) and silymarin (100 mg/kg), respectively. All treatments were carried out for 28 d. After sacrifice of the rats, biomarkers of oxidative stress [superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione-S-transferase (GST), advanced oxidation protein products (AOPP), malondialdehyde (MDA)], and liver injury [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total protein, albumin, bilirubin] were studied in serum and tissue using standard protocols and diagnostic kits. Inflammatory markers [tumor necrosis factor (TNF-α), interleukin (IL)-6, IL-10 and interferon (IFN)-γ] in serum were evaluated using ELISA-based kits. The effect of baicalin on liver was also analyzed by histopathological examination of tissue sections.RESULTSFluoxetine-treated rats showed elevated levels of the serum liver function markers (total bilirubin, ALT, AST, and ALP) and inflammatory markers (TNF-α, IL-6, IL-10 and IFN-γ), with a decline in total protein and albumin levels. Biochemical markers of oxidative stress such as SOD, CAT, GST, GSH, MDA and AOPP in the liver tissue homogenate were also altered indicating a surge in reactive oxygen species leading to oxidative damage. Histological examination of liver tissue also showed degeneration of hepatocytes. Concurrent administration of baicalin (50 and 100 mg/kg) restored the biomarkers of oxidative stress, inflammation and hepatic damage in serum as well as in liver tissues to near normal levels.CONCLUSIONThese findings suggested that long-term treatment with fluoxetine leads to oxidative stress via the formation of free radicals that consequently cause inflammation and liver damage. Concurrent treatment with baicalin alleviated fluoxetine-induced hepatotoxicity and liver injury by regulating oxidative stress and inflammation.     

黄皮酰胺的合成

根据推测的生源关系,以仿生路线合成了有保肝活性的植物成分黄皮酰胺。