• Natural Product Sciences
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• v.17 no.3
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• pp.165-174
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• 2011

Naturally occurring small molecules from plants, microorganisms, and animals allow the design of drugs that can be beneficial in virtually all kinds of human diseases. Liver diseases with diverse etiologies such as viral infection, chemical intoxication, and metabolic fat accumulation are one of the leading causes of human mortality. Unfortunately, however, there are few effective drugs available capable of stopping or reversing the progress of liver disease. Here, we discuss the current advances in developing hepatoprotective natural products for several arrays of liver disease pathogenesis.

• Korean Journal of Pharmacognosy
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• v.28 no.3
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• pp.156-161
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• 1997

For the search of hepatoprotective compounds from the folk medicines, 14 natural products which have been traditionally used as hepatoprotective drugs in Korea were extracted with methanol. The extracts were screened for the antioxidant activity on lipid peroxidation induced by Fenton reaction in rat homogenate and Ac2F cell toxicity by t-hydroperoxide. Dendrobium moniliforme and Castanea crenata were chosen for the further investigation and its therapeutic effects on the liver damage induced by carbon tetrachloride in rats were evaluated. Oral administration of the extracts reduced the aspartate aminotransferase(AST) and alanine aminotransferase(ALT) activities in the serum of the carbon tetrachloride intoxicated rat. And the treatment of the extracts prevented the decrease of aminopyrine N-demethylation and aniline hydroxylation activities of the carbon tetrachloride-intoxicated rat liver. These results suggest that oral administration of Dendrobium moniliforme and Castanea crenata is effective in recovering the liver function in $CCl_4-treated$ rats.

• Korean Journal of Pharmacognosy
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• v.21 no.3
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• pp.223-234
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• 1990

Hepatoprotective activities of 26 traditional Korean herbal prescriptions described in Donghibogam were evaluated in vivo and in vitro screening system. Twenty one prescriptions appeared to be active. Six prescriptions among them showed highly significant hepatoprotective activities; Shihogyegy-Tang(柴胡桂枝湯), Soshiho-Tang(小柴胡湯), Shiho plus Younggolmoryo-Tang(柴胡加龍骨牡蠣湯), Yinjinho-Tang(茵蔯蒿湯), Yinsam-Tang(人蔘湯) and Shashim-Tang(瀉心湯). Shihogyegy-Tang was most active. They reduced the release of transaminases from dissociated hepatocytes by thioacetamide, and serum transaminases and alkaline phosphatase activities of rat with carbontetrachloride-induced hepatitis. They inhibited significantly lipid peroxidation and cellular fatty change of liver by carbontetrachloride.

• Herbal Formula Science
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• v.16 no.1
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• pp.117-130
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• 2008

Korean traditional medicine has been used for the treatment of the various diseases based on both oriental medicinal theory and clinical trials. Thus, the prescriptions of Korean traditional medicine would be useful for the development of new therapeutics. This research focuses on the fundamental study in Korean traditional prescriptions for the development of new hepatoprotective agents. We found two prescriptions. Injinho-Tang and Osumogwa-Tang, showed the significant DPPH free radical scavenging and hepatoprotective effect, respectively. It is well-known that free radical scavenging effect is related to the prevention of various pathological events including liver injury. This paper deals with hepatoprotective effects on tacrine-induced cytotoxicity in Hep G2 cells, free radicals scavenging on both DPPH and superoxide of above two prescriptions. Hot water extract of Injinho-Tang did not show the significant hepatoprotective effect on tacrine-induced cytotoxicity in Hep G2 cells, however, it shows the significant scavenging effects for both DPPH and superoxide radicals. On the other hand, all of the hot water extracts of constituent herbal drugs in Injinho-Tang exhibited the promising protective effect on tacrine-induced cytotoxicity in Hep G2 cells. Of these, water extract of Rhei Rhizoma showed the most prominent effect on tacrine-induced cytotoxicity in Hep G2 cells. Bioassay-guided fractionation of Rhei Rhizoma extract has furnished four compounds, and their chemical structures have been identified by comparison of their spectral data with those of literature as chrysophanol (1), emodin (2), 3,5-dihydroxy-4'- methoxystilbene (3), and rhapontigenin (4), respectively. Among the isolated compounds, compounds 2-4 revealed the significant hepatoprotective effect in vitro when their $EC_{50}$ values compare with that of silybin, as a positive control. It also exhibited that emodin possessed the most hepatoprotective effect among these active compounds. In case of Osumogwa-Tang, its hot water extract showed the moderate protective effect on tacrine-induced cytotoxicity in Hep G2 cells. Hot water extract of Chaenomelis Fructus, one of the constituent herbal drug of this prescription, exhibited the significant hepatoprotective effect with $EC_{50}$ value of $7.8{\pm}0.1\;{\mu}g/ml$, however, it showed strong cytotoxicity in Hep G2 cells above the concentration of $25\;{\mu}g/ml$. It was revealed that both hot water extract of Evodiae Fructus and its butanol soluble fraction showed the moderate hepatoprotective effect but concentration-dependent activity in Hep G2 assay system. Two quinolone alkaloids, evocarpine and dihydroevocarpine, also tested for their hepatoprotective effects on tacrine-induced cytotoxicity in Hep G2 cells, however, these two compounds derived from the Evodiae Fructus as the major constituents did not show in vitro hepatoprotective effect. From these results, it would be necessary to further isolation of its hepatoprotective compounds from the butanol soluble fraction of the hot water extract of Evodiae Fructus.

• Biomolecules & Therapeutics
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• v.10 no.1
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• pp.1-6
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• 2002

The particle size of medicinal materials is an Important physical property that affects the phar-maceutical behaviors such as dissolution, chemical stability, and bioavailability of solid dosage forms. The size reduction of raw medicinal powder is needed to formulate insoluble drugs or slightly soluble medicines and to improve the pharmaceutical properties such as the solubility, the pharmaceutical mixing, and the dispersion. The objective of the present study is to evaluate physiological activity of amorphous and nano-particle prep-arations of insoluble drug, ursodeoxycholic acid (UDCA), which were made by three types of fine grinding mills. The change of physical properties of ground UDCA was conformed by Mastersiger microplus and X-ray diffraction. We have investigated hepatoprotective effects of the nano-particle preparations of UDCA by plan-etary mill, vibration rod mill and jet mill in $CCI_4$-induced oxidatively injured mouse liver. The results showed that nano-particle preparations of UDCA all decreased reactive oxygen sepecies generation and lipid peroxi-dation in $CCI_4$-induced oxidative stress mice. Among them, nano-particle preparations by vibration rod mill and jet mill showed more significantly hepatoprotective effects compared to intact UDCA and planetary mill-ground UDCA. These results suggest that ground UDCA with vibration rod mill and jet mill shows a high amorphous state and the improved dissolution.

• Journal of Life Science
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• v.22 no.1
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• pp.117-125
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• 2012

This study investigated the potential hepatoprotective benefits of Crassostrea gigas oyster hydrolysates. Oysters are known to have many biofunctional properties. In particular, oyster enzymatic hydrolysates produce substances with beneficial functions. The potential hepatoprotective effects of C. gigas hydrolysates against damage induced by tacrine were evaluated in vitro in HepG2 cells. Peptides were generated from C. gigas by enzymatic hydrolysis with Neutrase, Flavourzyme, or Protamex enzyme preparations. Tacrine treatment induced considerable cell damage in HepG2 cells, as shown by significant leakage of glutamic oxaloacetic transaminase (GOT) and lactate dehydrogenase (LDH). Cells treated with C. gigas hydrolysates showed an increased resistance to oxidative challenge compared to control cells, as revealed by higher cell survival against tacrine-induced hepatotoxicity. In addition, treatment with C. gigas hydrolysates reduced the leakage of GOT and LDH. These findings indicate that enzyme hydrolysates derived from C. gigas may be of benefit for developing hepatoprotective foods and drugs.

• Korean Journal of Pharmacognosy
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• v.30 no.2
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• pp.222-225
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• 1999

The protective effects of the water extracts of nine kinds of medicinal herbs, which have been reputed to having the hepatoprotective activity in Chinese herbal medicine, on BNL cl.2 cells using a MTT assay were investigated. Five extracts including Coriolus versica, Curcuma longa, Phellinus linteus, Po-lygonum aviculare, and Salvia miltiorrhiza showed the protective effects on BNL cl.2 cells damaged by $CCl_4$ with $ED_{50}$ values of less than $100\;{\mu}g/ml$. Silymarin had been used as a positive control.

• Toxicological Research
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• v.12 no.2
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• pp.251-258
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• 1996

Panax ginseng has been used for various diseases including hepatic disorders. The aim of the present study was to investigate the hepatoprotective effects of ethanol extract and saponin of Panax ginseng in thioacetamide-intoxicated rats and to compare with silymarin, a known hepatoprotective agent. Male Sprague-Dawley rats were given single intragastric administration of thioacetamide. Aqueous solutions of ethanol extract and saponin of Panax ginseng with or without silymarin were administered intragastrically daily for six days from four days before until one day after thioacetamide administration. At the end of the treatment, the rats were fasted overnight and sacrificed. As a result, thioacetamide caused significant increase in serum levels of AST, ALT, 5'-nucleotidase and bilirubin. Thioacetamide increased $Ca^++$ content but decreased protein content in liver tissue. These thioacetamide-induced biochemical changes were prevented both by ethanol extract of ginseng and silymarin, but not by ginseng saponin. Silymarin did not potentlate the effect of either ethanol extract or saponin of ginseng on these parameters. Thioacetamide-induced confluent necrosis was not protected by the test drugs. In conclusion, ethanol extract of ginseng protects the liver possibly by stabilizing the cell membrane and by inhibiting thioacetamide-induced $Ca^++$ increase in the hepatocytes, which was comparable to that of silymarin.

• Korean Journal of Pharmacognosy
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• v.33 no.1 s.128
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• pp.5-12
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• 2002

This study was performed to evaluate hepatoprotective effect of Daewhang-whangryunhaedok-Tang(DWT) on liver injured rats induced by $CCl_4$ and the acute oral toxicity of it in mice. The activities of serum transaminase(ALT/AST), alkaline phosphatase(ALP) and lactic dehydrogenase (LDH), the levels of serum total cholesterol(TC) and triglyceride(TG), change of liver enlargement, and inhibitory activities of lipid peroxidation, catalase and glutathione-S-transferase(GST) in liver microsome were determined in hepatotoxic rats induced by $CCl_4$ DWT DWT was significantly reduced the serum ALT, AST, ALP, LDH, TC and TG levels. And, the increase of lipid peroxidation, decrease of catalase and GST activities in the liver microsome of $CCl_4$-intoxicated rat were significantly improved by the treatment of DWT. Male and female mice were administered maximum dosages of 5,000 mg/kg b.w. of DWT. After single oral administration of DWT to mice, we observed them daily for 2 weeks. DWT did not induce any toxic signs in the mortalities, clinical signs, body weight changes, and gross necropsy findings of mice. Based on these results, it is concluded that DWT may have the hepatoprotective effect on $CCl_4$ induced hepatotoxicity in rats. Also, DWT may have no side effect and its $LD_{50}$ value may be over 5,000 mg/kg b.w. in mice.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.218-223
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• 2018

The liver is an essential organ for the detoxification of exogenous xenobiotics, drugs and toxic substances. The incidence rate of non-alcoholic liver injury increases due to dietary habit change and drug use increase. Our previous study demonstrated that Ecklonia stolonifera (ES) formulation has hepatoprotective effect against alcohol-induced liver injury in rat and tacrine-induced hepatotoxicity in HepG2 cells. This present study was designated to elucidate hepatoprotective effects of ES formulation against carbon tetrachloride ($CCl_4$)-induced liver injury in Sprague Dawley rat. Sixty rats were randomly divided into six groups. The rats were treated orally with ES formulation and silymarin (served as positive control, only 100 mg/kg/day) at a dose of 50, 100, or 200 mg/kg/day for 21 days. Seven days after treatment, liver injury was induced by intraperitoneal injection of $CCl_4$ (1.5 ml/kg, twice a week for 14 days). The administration of $CCl_4$ exhibited significant elevation of hepatic enzymes (like AST and ALT), and decrease of antioxidant related enzymes (superoxide dismutase, glutathione peroxidase and catalase) and glutathione. Then, it leaded to DNA damages (8-oxo-2'-deoxyguanosine) and lipid peroxidation (malondialdehyde). Administration of ES formulation inhibited imbalance of above factors compared to $CCl_4$ induced rat in a dose dependent manner. Real time PCR analysis indicates that CYP2E1 was upregulated in $CCl_4$ induced rat. However, increased gene expression was compromised by ES formulation treatment. These findings suggests that ES formulation could protect hepatotoxicity caused by $CCl_4$ via two pathways: elevation of antioxidant enzymes and normalization of CYP2E1 enzyme.