Hepatoprotective Drugs for the Treatment of Virus-Induced Chronic Hepatitis: From Hypercarcinogenic State to Hypocarcinogenic State

Okamoto, Toshihiro; Kajino, Kazunori; Hino, Okio

doi:10.1254/jjp.87.177

Cited by 18 publications

(10 citation statements)

References 20 publications

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“…Angelica Dahuricae Radix contains various compounds including isoimperatorin, imperatorin, oxypeucedanin, byakangelicol, and byakangelicin. Of these agents, imperatorin, which is found in various plants used in traditional medicine, has recently been shown to have an inhibitory effect on mice concanavalin A-induced hepatitis (Okamoto et al, 1987). However, to the best of our knowledge, no studies conducted to date have reported the mechanism by which the anti-nociceptive and antiinflammatory action of methanol extract of Angelicae Dahuricae Radix (MEAD) occurs.…”

Section: Discussionmentioning

confidence: 99%

Anti-Nociceptive and Anti-Inflammatory Effects of Angelicae Dahuricae Radix Through Inhibition of the Expression of Inducible Nitric Oxide Synthase and NO Production

Kang¹,

Chae²,

Oh³

et al. 2008

Am. J. Chin. Med.

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The extract of Angelicae dahuricae radix has traditionally been used as an anti-noceptive remedy in China. In this study, the methanol extract of Angelicae dahuricae radix (MEAD) was evaluated to determine if it has anti-noceptive and anti-inflammatory action. The anti-nociceptive activities of MEAD were evaluated by determining the writhing response and sleeping time, as well as by a formalin test. In addition, the anti-inflammatory activities of MEAD were evaluated by a vascular permeability test as well as by measuring the carrageenan-induced paw edema and conducting a myeloperoxidase (MPO) assay. MEAD (600 and 1200 mg/kg) exhibited anti-inflammatory effects on acetic acid-induced vascular permeability, carrageenan-induced paw edema, and MPO activity. Moreover, the results of the formalin test, the acetic acid-induced writhing response and the pentobarbital-induced sleeping time indicated that MEAD had anti-nociceptive effects that occurred in a concentration-dependent manner. To determine the mechanism by which MEAD exerted its effects on the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) by treated murine macrophage RAW 264.7 cells was evaluated. Similar to the in vivo activities, both the iNOS expression and NO production were significantly suppressed by MEAD in a dose-dependent manner. Furthermore, MEAD inhibited the activating phosphorylation of ERK1/2. These results provide a scientific basis that explains the mechanism by which Angelicae dahuricae radix relieves inflammatory pain.

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Section: Discussionmentioning

confidence: 99%

Anti-Nociceptive and Anti-Inflammatory Effects of Angelicae Dahuricae Radix Through Inhibition of the Expression of Inducible Nitric Oxide Synthase and NO Production

Kang¹,

Chae²,

Oh³

et al. 2008

Am. J. Chin. Med.

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“…Counteracting the effects of Hepatitis C Virus (HCV) through the use of coumarins has proved challenging as only a small number, primarily osthole, are capable of inhibiting HCV replication and/or proliferation, this counteracting the progression of hepatitis C into hepatocarcinoma [136]. The action of osthole causes a strong reduction of plasma alanine aminotransferase and also inhibits caspase-3 activation [137].…”

Section: Structure Activity Relationships (Sars) Referencementioning

confidence: 99%

The Structure and Pharmacological Functions of Coumarins and Their Derivatives

Wang²,

Xu³

et al. 2009

CMC

255

132

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Coumarins are of many different structures. They constitute an important class of pharmacological agents possessing a range of different physiological activities including anti-cancer, anti-oxidant, anti- inflammation, anti-HIV, anti-coagulant, anti-bacterial, analgesic and comparative immune-modulation. Recently, coumarins have attracted intense research interest. Of great interest is the possibility that this class of molecules could be a source of drugs for the therapy of several diseases. These include recent insights into inhibiting cell proliferation by interfering with mitotic spindle microtubule function, decrease Matrix Metalloproteinase (MMP) activity, block the cell cycle in the S or G2/M phases to interfere with processes of cell division, suppress O2(-) generation in leukocytes, inhibit different protein kinases, modulate the signalings, induce carcinogen-detoxifying enzymes glutathione S-transferases (GSTs) and/or NAD(P)H quinine oxidoreductase (NQO1), suppress the phosphorylation of Akt/PKB as a mechanism inhibiting inflammation, progress in structure modification to increase in anti-fungal action, to broaden against bacteria spectrum, to enhance inhibiting activities of nitric oxide synthase (NOS) and cyclooxygenase (COX), to strengthen anti-oxidant activity and to exhibite a much higher cytotoxicity against human umbilical vein endothelial cell (HUVEC). With fewer non-hemorrhagic side effects than the indanedione derivatives, they can be applied as an oral anticoagulant commonly for preventing venous thromboembolism following orthopedic surgery, recurrent myocardial infarction and the treatment of systemic embolism in atrial fibrillation, together with the significant advances in the basis of drug action. It is therefore useful to build up some correlations with the data available in order to better explore the molecular and cellular mechanism of coumarin action in the treatment of diseases. This review will focus on recent advances in molecular and cellular mechanisms of coumarin action involved with the relationship between structure and activity.

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“…Osthole, a coumarin derivative contained in many medicinal plants especially in Boenninghausenia albiflora , was reported to protect against liver injury, and these effects are related to the presence of 7-methoxy and 3-methyl-2-butenyl groups in the structure [53,54]. Due to its low toxicity, osthole appears to be suitable for the treatment of chronic hepatitis and can be used as a lead compound for further development of orally ingested hepatoprotective drugs.…”

Section: Biological Activities Of Extracts and Ingredients Of Medicinmentioning

confidence: 99%

A survey of Chinese herbal ingredients with liver protection activities

et al. 2007

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A literature survey was conducted on herbs, their preparations and ingredients with reported liver protection activities, in which a total of 274 different species and hundreds of active ingredients have been examined. These ingredients can be roughly classified into two categories according to their activities: (1) the main ingredients, such as silybin, osthole, coumarin, glycyrrhizin, saikosaponin A, schisandrin A, flavonoids; and (2) supporting substances, such as sugars, amino acids, resins, tannins and volatile oil. Among them, some active ingredients have hepatoprotective activities (e.g. anti-inflammatory, anticancer, antioxidant, immunomodulating and liver cirrhosis-regulating effects). Calculation of physicochemical parameters indicates that the main ingredients with negative and positive Elumo values possibly display their hepatoprotective effects through different mechanisms, such as antioxidative, anti-inflammatory and immunomodulating effects. As the combination of herbs may achieve some treatment effects synergistically and/or additively, it is common in Chinese medicine to use mixtures of various medicinal herbs with pharmacologically active compounds to have synergistic and/or additive effects, or to reduce harmful effects of some pharmacologically active compounds. In particular, the active compounds with Clog P around 2 are suitable for passive transport across membranes and accessible to the target sites. Thus, Elumo and Clog P values are good indicators among the calculated parameters.Seven different physicochemical parameters (MW, Clog P, CMR, μ, Ehomo, Elumo and Hf) and four major biological activities (antioxidant, anti-inflammatory, antiviral/antitumor and immunomodulating) are discussed in this review. It is hoped that the discussion may provide some leads in the development of new hepatoprotective drugs.

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Hepatoprotective Drugs for the Treatment of Virus-Induced Chronic Hepatitis: From Hypercarcinogenic State to Hypocarcinogenic State

Cited by 18 publications

References 20 publications

Anti-Nociceptive and Anti-Inflammatory Effects of Angelicae Dahuricae Radix Through Inhibition of the Expression of Inducible Nitric Oxide Synthase and NO Production

Anti-Nociceptive and Anti-Inflammatory Effects of Angelicae Dahuricae Radix Through Inhibition of the Expression of Inducible Nitric Oxide Synthase and NO Production

The Structure and Pharmacological Functions of Coumarins and Their Derivatives

A survey of Chinese herbal ingredients with liver protection activities

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