Antihepatotoxic Principles of Curcuma longa Rhizomes1.

An extract of the crude drug "ukon", the rhizomes of CURCUMA LONGA, exhibited intense preventive activity against carbon tetrachloride-induced liver injury IN VIVO and IN VITRO. The extract was subjected to fractionation by monitoring the activity by the IN VITRO assay methods employing carbon tetrachloride- and galactosamine-produced cytotoxicity in primary cultured rat hepatocytes. Curcuminoids were shown to possess significant antihepatotoxic action. The liver protective effects of some analogues of ferulic acid and p-coumaric acid, probable metabolites of the curcuminoids, were also evaluated.     

茵陈化学成分的分离与鉴定

目的:分离、鉴定茵陈提取物中的化学成分。方法:采用硅胶柱、ODS开放柱和制备液相等色谱方法分离茵陈提取物,并通过NMR和MS等谱学技术确定分离出的化合物结构。结果:从茵陈提取物中分离得到8个化合物,分别鉴定为7-羟基香豆素(1)、5,7-二甲氧基香豆素(2)、7-羟基-8-甲氧基香豆素(3)、7,8-二羟基香豆素(4)、槲皮素(5)、山柰酚(6)、异鼠李素-3-O-β-D-半乳糖苷(7)、咖啡酸(8)。化合物1～4、7为首次从蒿属植物中分离得到。结论:本试验结果可为茵陈的进一步开发利用提供依据。     

Isoputrin and Butrin, the Antihepatotoxic Principles of Butea monosperma Flowers1.

Since an extract from the flowers of BUTEA MONOSPERMA, a plant drug used in India for the treatment of liver disorders, showed significant activity in different models of liver damage, the extract was fractionated by solvent partitioning and HPLC, and activity monitored by means of CCl (4)- and GalN-induced liver lesion IN VITRO. The antihepatotoxic principles isolated consisted of two known flavonoids, isobutrin (3, 4, 2', 4'-tetrahydroxychalcone-3, 4'-diglucoside), and the less active butrin (7, 3', 4'-trihydroxyflavanone-7, 3'-diglucoside). For qualitative and quantitative analysis of isobutrin and butrin in extracts of BUTEA MONOSPERMA flowers a HPLC system was developed.     

Vicenin 2 isolated from Artemisia capillaris exhibited potent anti-glycation properties

Vicenin 2, isolated from a traditionally used medicinal plant Artemisia capillaris, is a 6,8-di-C-glucoside of apigenin which has been previously reported to possess a wide variety of pharmacological activities including antioxidant, anti-inflammatory, anti-cancer, and hepatoprotective. However, there have not been any reports concerning its anti-diabetic potential until now. Therefore, in the present study, we evaluated the anti-diabetic potential of vicenin 2 via α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), rat lens aldose reductase (RLAR), and advanced glycation end products (AGE) formation inhibitory assays. Vicenin 2 strongly inhibited α-glucosidase, PTP1B, and RLAR in the corresponding assays. In addition, vicenin 2 inhibited the formation of both fluorescent AGE and nonfluorescent AGE, e.g., CML, as well as the level of fructosamine in glucose–fructose-induced bovine serum albumin (BSA) glycation. In the test system, vicenin 2 suppressed glycation-induced protein oxidation by attenuating the formation of protein carbonyl groups as well as by inhibiting the modification of protein thiol groups. Moreover, vicenin 2 was found to be a potent inhibitor of glycation-induced formation of amyloid cross-β structures in BSA. Taken together, vicenin 2 might be a useful lead for the development of multiple target-oriented therapeutic modalities for the treatment of diabetes and diabetes-associated complications.     

Inhibitory activity of coumarins from Artemisia capillaris against advanced glycation endproduct formation

Since glycation can lead to the onset of diabetic complications due to chronic hyperglycemia, several indigenous Artemisia species were evaluated as potential inhibitors of advanced glycation endproducts (AGE). Among them, the Artemisia capillaris plant demonstrated the highest AGE inhibitory activity. Repeated column chromatography was performed to isolate a new acylated flavonoid glycoside, acacetin-7-O-(6″-O-acetyl)-β-D-glucopyranosyl-(1→2)[α-L-rhamnopyranosyl]-(1→6)-β-D-glucopyranoside, along with 11 known flavonoids (acacetin-7-O-β-D-glucopyranosyl-(1→2)[α-L-rhamnopyranosyl]-(1→6)-β-D-glucopyranoside, linarin, quercetin, hyperoside, isorhamnetin, isorhamnetin 3-galactoside, isorhamnetin 3-glucoside, isorhamnetin 3-arabinoside, isorhamnetin 3-robinobioside, arcapillin, and cirsilineol), six coumarins (umbelliferone, esculetin, scopoletin, scopolin, isoscopolin, and scoparone), and two phenolic derivatives (4,5-di-O-caffeoylquinic acid and chlorogenic acid). In determining the structure-activity relationship (SAR), it was found that the presence and position of hydroxyl group of test coumarins (coumarin, esculin, isoscopoletin, daphnetin, 4-methylcoumarin, and six isolated coumarins) may play a crucial role in AGE inhibition. A free hydroxyl group at C-7 and a glucosyl group instead of a methoxyl group at C-6 are two important parameters for the inhibitory potential of coumarins on AGE formation. A. capillaris and five key AGE inhibitors, including 4,5-di-Ocaffeoylquinic acid, umbelliferone, esculetin, esculin, and scopoletin, were identified as potential candidates for use as therapeutic or preventive agents for diabetic complications and oxidative stress-related diseases. We understand this to be the first detailed study on the SAR of coumarins in AGE inhibition.     

茵陈中7-甲氧基香豆素的分离与含量测定

目的建立分离、测定茵陈中 7 甲氧基香豆素含量的方法。方法采用水煎、氯仿萃取与硅胶柱分离制备 7 甲氧基香豆素 ;并利用高效液相色谱法 ,对不同产地的 1 4个茵陈样本中 7 甲氧基香豆素的含量进行测定。以甲醇 水 冰醋酸 ( 5 2∶4 8∶4 )为流动相 ,检测波长 3 2 0nm。结果平均加样回收率为 99 3 % ,RSD =4 2 %。线性范围 0 1 2 5～ 6 2 5mg/L,线性关系良好 ,回归方程为A =693 1 0C -5 77,相关系数r=0 9999。结论不同产地的茵陈中 7 甲氧基香豆素含量具有显著差异 ;7 甲氧基香豆素HPLC测定具有良好的准确度和重现性 ,可作为茵陈药材中 7 甲氧基香豆素的常规分析方法     

High-performance liquid chromatographic analysis for quantitation of marker compounds of Artemisia capillaris thunb.

Two stable high-performance liquid chromatography (HPLC) methods were developed that could quantitatively analyze 10 major marker compounds of Artemisia capillaris Thunb and could also distinguish among ‘Injinho’ and ‘Myeon-injin’ and ‘Haninjin’ — A. capillaris collected in autumn, A. capillaris collected in spring and A. iwayomogi, which can be misused as ‘Injinho’ in Korean herbal drug markets. The first HPLC method was a reversed-phase chromatography using a C18 column with an isocratic solvent system of phosphoric acid (0.05%) and acetonitrile at the flow rate of 1.0 mL/min, ultraviolet (UV) detection wavelength at 254 nm and column temperature at 40°C. Calibration and quantitation were made by using acetaminophen as an internal standard (I.S-A) and chlorogenic acid (1) was determined within 20 min. The second HPLC method was a reversed-phase chromatography using a C18 column with a gradient solvent system of phosphate buffer (0.015 M, pH 6) and acetonitrile at the flow rate of 1.0 mL/min, UV detection wavelength at 254 nm and column temperature at 40°C. Calibration and quantitation were made by using ethylparaben as an internal standard (I.S-B) and 3,5-di-O-caffeoylquinic acid (2), 3,4-di-O-caffeoylquinic acid (3), 4,5-di-O-caffeoylquinic acid (4), hyperoside (5), isoquercitrin (6), isorhamnetin 3-O-robinobioside (7), isorhamnetin-3-O-galactoside (8), isorhamnetin-3-O-glucoside (9) and scoparone (10) were determined within 60 min. Pattern recognition analysis of data from the 60 samples classified them clearly into three groups. These assay methods could be applied for QA/QC of A. capillaris and Artemisia iwayomogi.     

Antihepatotoxic Actions of Allium sativum Bulbs1.

Garlic constituents, the volatile oil, alliin, S-allylmercaptocysteine (ASSC) and S-methylmercapto-cysteine (MSSC) were subjected to assay for their antihepatotoxic activity using the IN VITRO and IN VIVO liver damage models. Marked inhibitory activity was found with the volatile oil, ASSC and MSSC in carbon tetrachloride (CCl (4))- and galactosamine (GalN)-induced cytotoxicity in primary cultured rat hepatocytes as model systems. ASSC exhibited a remarkable inhibitory action and the volatile oil, alliin and MSSC showed tendencies to elicit protective actions in GalN-produced liver lesion in rats. The volatile oil inhibited CCl (4)-induced free radical formation and lipid peroxidation, indicating that anti-oxidative activity participates in the inhibitory effect of the volatile oil in CCl (4)-evoked liver damage.     

Antihepatotoxic Actions of Ginsenosides from Panax ginseng Roots1

The antihepatotoxic effects of ginsenosides, saponins from PANAX GINSENG, and their aglycones were investigated utilizing carbon tetrachloride (CCl (4))- and galactosamine (GalN)-induced cytotoxicity in primary cultured rat hepatocytes. Prominent protective actions were found with 20( S)-ginsenoside-Rh (2), 20( R)-ginsenoside-Rg (3) and prosapogenin of ginsenoside-Ro, 20( R)- and 20( S)-ginsenoside-Rs in CCl (4)-produced cytotoxicity, and 20( S)-ginsenoside-Rh (1) and prosapogenin of 20( S)-ginsenoside-Rs were effective in preventing GalN-induced liver cell damage. The antihepatotoxic effects of chikusetsusaponins, saponins of PANAX JAPONICUS, were also examined. The structure-activity relationship is discussed.     

A comprehensive study on in vitro and in vivo toxicological evaluation of Artemisia capillaris

Artemisia capillaris (AC) has been used as an alternative therapy in obesity, atopic dermatitis, and liver diseases through several biological activity including anti-steatotic, antioxidant, and anti-inflammatory activities. Despite its ethnomedicinal benefits, no sufficient background information is available about the long-term safety and genotoxicity of the AC extract. Therefore, the present study was carried out to investigate the 13-week subchronic toxicity and genotoxicity of the AC extract according to the test guidelines published by the Organization for Economic Cooperation and Development. In the 13-week toxicity study using doses of 25, 74, 222, 667, and 2000 mg/kg body weight, oral administration of the AC extract in male and female rats did not result in any significant adverse effects in food/water consumption, body weight, mortality, hematology, serum biochemistry, organ weight and histopathology. Accordingly, the no-observed-adverse-effect level in rats of both genders was established for the AC extract at 2000 mg/kg/day, the highest dose level tested. In addition, the AC extract was not genotoxic in a battery of tests including Ames test, in vitro chromosome aberration assay and in vivo micronucleus assay. In conclusion, we demonstrated that the AC extract is considered as a safe traditional medicine for human consumption.     

Chemical composition and antimicrobial activity of the essential oils of Artemisia scoparia and A. capillaris

The chemical composition of the essential oils obtained from Artemisia scoparia Waldst. et Kitamura and Artemisia capillaris Thunb. was analyzed by GC/MS. The essential oil of A. scoparia was rich in camphor (11.0 %), 1,8-cineole (21.5 %), and beta-caryophyllene (6.8 %) as the major compounds, whereas A. capillaris oil was rich in beta-pinene (9.4 %), beta-caryophyllene (11.1 %), and capillene (32.7 %). The essential oils and some of their major compounds were tested for their antimicrobial activity against 15 different genera of oral bacteria. The essential oils of A. scoparia and A. capillaris exhibited considerable inhibitory effects against all oral bacteria tested, while their major components demonstrated various degrees of growth inhibition.     

Inhibition of 5-lipoxygenase and skin inflammation by the aerial parts of Artemisia capillaris and its constituents

The aerial parts of Artemisia capillaris Thunberg (Compositae) have been used in Chinese medicine as a liver protective agent, diuretic, and for amelioration of skin inflammatory conditions. This study was conducted to establish the scientific rationale for treating skin inflammation and to find active principles from A. capillaris. To accomplish these goals, the 70% ethanol extract of the aerial parts of A. capillaris (AR) was prepared and its 5-lipoxygenase (5-LOX) inhibitory action was studied since 5-LOX products are known to be involved in several allergic and skin inflammatory disorders. AR showed potent inhibitory activity against 5-LOX-catalyzed leukotriene production by ionophore-induced rat basophilic leukemia-1 cells, with an IC₅₀ of < 1.0 μg/mL. Nine major compounds, scopoletin, scopolin, scoparone, esculetin, quercetin, capillarisin, isorhamnetin, 3-O-robinobioside, isorhamnetin 3-O-galactoside and chlorogenic acid, were isolated from A. capillaris, and their effects were examined to identify the active principle(s). Several coumarin and flavonoid derivatives were found to be 5-LOX inhibitors. In particular, esculetin and quercetin were potent inhibitors, with IC₅₀ values of 6.6 and 0.7 μM, respectively. Against arachidonic acid-induced ear edema in mice, AR, and esculetin strongly inhibited edematic response. AR and esculetin also inhibited delayed-type hypersensitivity response in mice. In conclusion, AR and some of their major constituents are 5-LOX inhibitors, and these in vitro and in vivo activities may contribute to the therapeutic potential of AR in skin inflammatory disorders in traditional medicine.     

Antihepatotoxic Activity of Spilanthes ciliata

Abstract

The ethanol extract of the whole plant of Spilanthes ciliata was screened for its hepatoprotective effects in Wistar rats. A significant hepatoprotective effect was obtained against paracetamol-induced hepatic damage as evident from decreased levels of serum enzymes and an almost normal histological architecture of the liver, following treatment with the plant extract prior to paracetamol overdose-induced liver damage. The extract was also effective in increasing the choleretic activity of anaesthetized normal rats. The extract shortened hexobarbitone-induced sleeping time in mice, which was increased by carbon tetrachloride (CCl₄) treatment, besides showing significant antilipid peroxidant effects in vitro.     

Analyzing of the volatile chemical constituents in Artemisia capillaris herba by GC-MS and correlative chemometric resolution methods

The volatile chemical constituents in traditional Chinese medicine (TCM), Artemisia capillaris herba, were determined by gas chromatography-mass spectrometry (GC-MS). The acquired two-dimensional data were resolved by correlative chemometric resolution methods. The noise in the raw data is pretreated by roughness penalty smoothing method. With the data denoised, heteroscedastic noise and signal-to-noise ratio were decreased apparently, which was favorable to the determination of component number. The selective range can be extracted from rankmap obtained by fixed size moving window evolving factor analysis (FSMWEFA) conveniently. The overlapped chromatographic peaks were resolved into pure chromatograms and pure spectra with evolving window orthogonal projection (EWOP). The purity of the resolved pure spectra were improved furthermore with the heteroscedastic noise decreased through roughness penalty smoothing method, although the basic structure of the raw data changes little. Qualitative analysis was performed by similarity search in NIST147 and Willey library. Pure chromatograms are in favor of quantitative analysis, which was obtained by total volume integration. Forty-two of seventy-five separated constituents in essential oil, accounting for 89.03% of the total content, were identified. The result proves the combined approaches to be powerful for the analysis of complex herbal samples.     

Antihepatotoxic principles of Solanum capsicastrum

Two new steroidal alkaloids named capsimine and isocapsicastrine were isolated from the root bark of Solanum capsicastrum. Their structures were elucidated by chemical degradation and spectral data as (22R, 25R)-22,26-epiminocholest-5-ene-3 beta, 16 alpha-diol and (22S,25S)-O(3)-beta-D-glucopyranosyl-22,26-epiminocholest-5-ene-3 beta-16 alpha-diol, respectively. Capsicastrine, capsicastrine acetate, isoteinemine acetate, and etioline exhibited strong activity against liver damage induced by CCl4.     

Antihepatotoxic activity of Phyllanthus fraternus

Different fractions of alcoholic extracts of aerial parts and roots of Phyllanthus fraternus Webster (Euphorbiaceae) were screened for antihepatotoxic activity on carbon tetrachloride induced liver damage in albino rats. The degree of protection was measured using biochemical parameters like serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), total protein (TP) and total albumin (TA). The methanol fraction was found to be the most active, which was further supported by a significant recovery of hepatocytes in the histopathological study of the liver showing almost complete normalization of the tissues as neither the fatty accumulation nor the necrosis was observed.