Steady-state pharmacokinetics and tissue distribution of anthraquinones of Rhei Rhizoma in rats

Aim of the study

Rhei Rhizoma, the rhizome of Rheum palmatum L. (RP), is a popular herb in clinical Chinese medicine. RP is abundant in polyphenolic anthraquinones, which have been reported to show various beneficial bioactivities. This study investigated the pharmacokinetics and tissue distribution of anthraquinones following seven-dose administration of RP decoction to rats.

Materials and methods

Six Sprague-Dawley rats were given 2.0 g/kg of RP twice daily for seven doses and blood samples were collected at designated time after the 7th dose. Another six rats were sacrificed at 30 min after the 7th dose and organs including liver, kidney, lung and brain were collected. Serum and tissue specimens were assayed by HPLC before and after hydrolysis with β-glucuronidase and sulfatase, respectively.

Results

Pharmacokinetic analysis indicated that the anthraquinones in serum mainly presented as glucuronides/sulfates and contained higher ratio of sulfates when compared with single-dose administration of RP. Contrary to the finding in serum, tissue analysis discovered mainly free form of anthraquinone in most organs assayed, such as aloe-emodin and rhein in kidney, liver, lung; emodin in liver, lung; trace of chrysophanol in kidney and liver. In all brains, neither free forms nor their glucuronides/sulfates have been detected.

Conclusions

The glucuronides/sulfates of anthraquinones were the major forms in bloodstream, whereas the free forms of most anthraquinones were predominant in kidney and liver.     

Study on liver targeting effect of vinegar-baked Radix Bupleuri on resveratrol in mice

Background and purpose

Site-direct delivery is a desirable and elusive goal. In Traditional Chinese Medicine, this goal is usually met by coadministration with a kind of meridian guide drug (MGD). Vinegar-baked Radix Bupleuri (VBRB) is usually used to focus other drugs pharmacological effect on liver in Traditional Chinese Medicine (TCM). However, the scientific data for this effect are not available. In this paper, the liver targeting enhancing effect of VBRB on resveratrol was investigated.

Experimental approach

Mice, 144, were divided into four groups by random, resveratrol group as control and resveratrol coadministered with three different doses of VBRB peroral. Concentrations of resveratrol in different tissues were determined by HPLC and the target effeciency was evaluated by relative uptake efficiency (RUE) and relative targeting efficiency (RTE).

Key results

Compared to the control group, medium dose VBRB enhanced the targeting efficiency of resveratrol significantly, and the RUE and RTE were 1.79 and 46.9%, respectively. Meanwhile, it considerably reduced the distribution of resveratrol in lung and blood, the RUE and RTE in blood were 1.1, −22.6%, and were 0.88, −55.0% in lung, respectively. VBRB reduced the Cmax of resveratrol in almost all the tissues except for liver, heart and kidney, with the extent in the range of 26–61%. In addition, VBRB prolonged the retention time of resveratrol in liver, and shortened the retention time in other tissues.

Conclusions and implications

VBRB could enhance the distribution of resveratrol in liver, and reduce the distribution in other tissues, implying that VBRB might be a potential drug for achieving target therapy.     

Pharmacokinetic study of salvianolic acid A in beagle dog after oral administration by a liquid chromatography–mass spectrometry method: A study on bioavailability and dose proportionality

Ethnopharmacological relevance

Salvianolic acid A (SAA) is one of the main water-soluble components isolated from Salvia miltiorrhiza Bunge. Pharmacological researches revealed that it had various curative activities after oral and intravenous administration, including beneficial effects on diabetes and its complications, cardioprotective effect, anti-platelet aggregation, and so on. However, there is no report regarding the pharmacokinetics of SAA in beagle dogs after oral administration up to now.

Aim of the study

To study the pharmacokinetics of different doses of SAA in beagle dogs and figure out the absolute bioavailability and dose proportionality of SAA after oral administration.

Materials and methods

Male and female beagle dogs were orally administered SAA 5, 10 and 20 mg/kg randomly. The plasma drug concentration was detected by a rapid, sensitive and reproducible liquid chromatography–mass spectrometry (LC–MS) method. The pharmacokinetic parameters were calculated from plasma concentration–time data using the DAS pharmacokinetic software Data Analysis System Version 3.0 program.

Results

After single-dose oral administration of SAA, the mean peak plasma concentration (C_max) values for groups treated with 5, 10 and 20 mg/kg doses ranged from 14.38 to 38.18 µg/L, and the mean area under the concentration–time curve (AUC_(0–t)) values ranged from 38.77 to 130.33 (µg/L⋅ h). SAA showed lack of dose proportionality over the dose range 5–20 mg/kg, based on the power model. However, the increase in systemic exposure with dose appeared linear. The absolute bioavailability was calculated to range from 1.47% to 1.84%.

Conclusion

The pharmacokinetic properties of SAA in beagle dogs after oral administration were characterized as rapid oral absorption, quick clearance, and poor absolute bioavailability. Systemic exposure exhibited lack of dose proportionality over the dose range 5–20 mg/kg. Furthermore, a readily preparative LC–MS method was demonstrated in this study for the research of traditional Chinese medicine.     

The effects of wine-processing on ascending and descending: The distribution of flavonoids in rat tissues after oral administration of crude and wine-processed Radix scutellariae

Ethnopharmacological relevance

Ascending and descending theory is a core principle of traditional Chinese medicine (TCM) theories. It plays an essential role in TCM clinical applications. Some TCM medicine has specific properties, which could alter the inclination and direction of their actions. The properties of the ascending and floating process of one herbal medicine are affected by means of herb processing. Wine-processing, which is sautéing with rice wine, is one of the most popular technologies of herb processing. Wine-processing increases the inclination and direction of its actions, thereby producing or strengthening their efficacy in cleaning the upper-energizer heat.Radix scutellariae, the dried roots of Scutellaria baicalensis Georgi, is a well-known TCM used for the treatment of inflammation, pyrexia, jaundice, etc. Recently, wine-processed Radix scutellariae was normally applied in clinical studies for the treatment of upper-energizer syndrome. In order to investigate the effects of wine-processing on ascending and descending of Radix scutellariae, the comparative study of distribution of flavonoids in rat tissues of triple energizers (SanJiao-upper, middle, lower jiao) after oral administration of crude and wine-processed Radix scutellariae aqueous extracts was carried out.

Materials and methods

The rats were randomly assigned to two groups and orally administered with crude and wine-processed Radix scutellariae aqueous extracts, respectively. At different pre-determined time points after administration, the concentrations of compounds in rat tissue homogenate were determined, and the main tissue pharmacokinetic parameters were investigated. Tissue pharmacokinetic parameters including AUC_0–t, t_1/2, T_max and C_max were calculated using DAS 2.0. An unpaired Student t-test was used to compare the differences in tissue pharmacokinetic parameters between the two groups. All the results were expressed as arithmetic mean±S.D.

Results

The parameters of C_max and AUC_0–t of some flavonoids in wine-processed Radix scutellariae were remarkably increased (p<0.05, p<0.01, p<0.001) in the rat upper-energizer tissues (lung and heart) compared with those of the crude group. However, in the rat middle- and lower-energizer tissues (spleen, liver and kidney), the C_max and AUC_0–t of some flavonoids were significantly decreased (p<0.05, p<0.01) compared with the crude group. The main explanation for these differences seems to the effects of wine-processing on ascending and descending theory.

Conclusions

All of these differences in the distribution of triple energizers after oral administration of crude and wine-processed Radix scutellariae aqueous extracts may lead to the increase of efficacy on the upper-energizer tissues and were in compliance with the ascending and descending theory. Therefore, wine-processing was recommended when Radix scutellariae was used for cleaning the upper-energizer heat and humidity. The obtained knowledge can be used to evaluate the impact of these differences on the efficacy of both the drugs in clinical applications and might be helpful in explaining the effects of wine-processing on ascending and descending theory.     

Studies on the analgesic,anti-inflammatory and antipyretic effects of Parquetina nigrescens leaf extract

Ethnopharmacological relevance

Parquetina nigrescens is a shrub that is commonly used in different parts of West Africa for the treatment of several ailments which includes pain, fever and inflammatory conditions.

Aim of the study

The present study was designed to investigate the analgesic, anti-inflammatory and antipyretic effects of the aqueous extract of Parquetina nigrescens leaves in rats.

Materials and methods

Five groups were used for each study, groups 1 and 5 served as control (saline) and reference (indomethacine) respectively, while groups 2–4 received the extract (50–200 mg/kg) orally. Formalin paw licking and hot plate latency tests were used for analgesic studies. Carrageenan oedema, cotton pellet granuloma and formaldehyde arthritis models were used to quantify the anti-inflammatory activities while the brewer’s yeast was used for inducing pyrexia.

Results

The results of the analgesic study show that the extract produced significant (p < 0.05) analgesia in the hot plate and in the formalin tests. In the anti-inflammatory study, Parquetina nigrescens produced significant (p < 0.05) inhibition of the various types of inflammation. The extract also inhibited the pyrexia induced by brewer’s yeast.

Conclusion

The result justifies the traditional uses of Parquetina nigrescens for the treatment of fever, inflammatory and painful conditions.     

Anti-hyperuricemic and nephroprotective effects of Modified Simiao Decoction in hyperuricemic mice

Ethnopharmacological relevance

Modified Simiao Decoction (MSD), based on clinical experience, has been used for decades and famous for its efficiency in treating hyperuricemic and gouty diseases.

Aim of the study

To investigate the effects of MSD on anti-hyperuricemic and nephroprotective effects are involved in potassium oxonate-induced hyperuricemic mice.

Materials and methods

The effects of MSD were investigated in hyperuricemic mice induced by potassium oxonate. MSD were fed to hyperuricemic mice daily at a dose of 0.45, 0.90, 1.80 g/kg for 10 days, and allopurinol (5 mg/kg) was given as a positive control. Serum and urine levels of uric acid and creatinine, and fractional excretion of uric acid (FEUA) were determined by colorimetric method. Its nephroprotective effects were evaluated by determining a panel of oxidative stress markers after the intervention in hyperuricemic mice. Simultaneously, protein levels of urate transporter 1 (URAT1) and organic anion transporter 1 (OAT1) in the kidney were analyzed by Western blotting.

Results

MSD could inhibit XOD activities in serum and liver, decrease levels of serum uric acid, serum creatinine and BUN, and increased levels of urine uric acid, urine creatinine, FEUA dose-dependently through down-regulation of URAT1 and up-regulation of OAT1 protein expressions in the renal tissue of hyperuricemic mice. It also effectively reversed oxonate-induced alterations on renal MDA levels and SOD activities in this model.

Conclusion

MSD processes uricosuric and nephroprotective actions by regulating renal urate transporters and enhancing antioxidant enzymes activities to improve renal dysfunction in hyperuricemic mice.     

Systemic exposure of quercetin after administration of feng-liao-chang-wei-kang granules to rats

Aim of study

The objective of this study was to observe the systemic exposure of quercetin (QCT) including its free and total concentration in rat blood samples following a single p.o. dose of Feng-Liao-Chang-Wei-Kang granules (FLCWKG).

Materials and methods

Six male rats were given the FLCHKG and the serial blood samples were collected. Fully or partially validated LC/MS/MS methods were developed to analyze the resulting biosamples. Various pharmacokinetic (PK) parameters were estimated from the plasma concentration versus time data using non-compartmental methods.

Results

Both methods for analysis of the free and total QCT plasma concentration are sensitive, specific, accurate and reliable. The PK parameters of free QCT after administration of FLCWKG, in comparison with total concentration, show a lower C_max (32.4 ± 8.2 ng/ml versus 164 ± 49 ng/ml), a lower AUC_{(0 → ∞)} (39.3 ± 6.9 ng/ml h versus 313 ± 16 ng/ml h), a shorter T_max (0.17 ± 0.00 h versus 0.83 ± 1.01 h) and a similar t_1/2 (3.90 ± 0.88 h versus 3.10 ± 1.94 h), MRT_(0 → t) (2.27 ± 0.10 h versus 2.86 ± 0.41 h).

Conclusions

Free QCT was quickly absorbed from gastrointestinal tract and circulated in blood at quite low concentration. The circulating flavonoids originating from this formula were dominantly conjugated derivatives.     

Glycyrrhizin accelerates the metabolism of triptolide through induction of CYP3A in rats

Ethnopharmacological relevance

Triptolide (TP), a major active component of Tripterygium wilfordii, possesses various pharmacological activities with narrow therapeutic window and severe toxicities. Glycyrrhizin (GL), the principal bioactive ingredient of licorice root extract, has been reported to be concomitantly administered with TP in treatment of rheumatoid arthritis with the aim of potentiated efficacy and reduced toxicity. The aim of the study is to investigate the effect of GL on the pharmacokinetic profiles of TP and related mechanisms.

Materials and methods

Male and female Wistar rats were randomly divided into two groups: Control group and GL group (pretreated with GL at 100 mg/kg/day for seven consecutive days). After oral administration of TP at a single dose of 450 μg/kg, plasma concentrations of TP were determined using HPLC–MS/MS and pharmacokinetic parameters were calculated by non-compartmental analysis using Phoenix WinNonlin 6.3 software. Since CYP3A is the primary isoform of cytochrome P450s responsible for the metabolism of TP, we further determined to what extent ketoconazole (KCZ), a potent CYP3A inhibitor, could influence the effect of GL on the pharmacokinetics of TP by comparing the pharmacokinetic profiles of TP in GL group (pretreated with GL) and GL+KCZ group (pretreated with both GL and KCZ), as well as verified whether pretreatment of GL could induce the activity of hepatic CYP3A by comparing the AUC parameters after intravenous administration of midazolam (MDZ), a typical probe drug for CYP3A, in rats pretreated with vehicle or GL.

Results

Our study revealed marked differences in pharmacokinetic profiling patterns of TP between male and female rats in the Control group; the plasma level of TP in males was far lower than that in females. After pretreatment with GL, the pharmacokinetic profiles of TP were significantly altered in both male and female rats; a remarkable decrease was found in the value of AUC_∞, MRT_∞ and t_1/2 in the GL group, compared with the Control group. But such a decrease was reversed by KCZ; compared with the GL group, the values of AUC_∞, MRT_∞ and t_1/2 were significantly increased in the GL+KCZ group. Pretreatment with GL notably increased the AUC_∞ of 1?-hydroxymidazolam (OH-MDZ) and the ratio of AUC_∞ of OH-MDZ to MDZ, demonstrating induction of the activity of CYP3A by GL.

Conclusion

Pretreatment with GL significantly accelerates the metabolic elimination of TP from the body mainly through induction of hepatic CYP3A activity. These results may help explain why toxicity of TP may be attenuated with concomitant use of GL.     

Antiurolithic effect of Bergenia ligulata rhizome: An explanation of the underlying mechanisms

Ethnopharmacological relevance

Bergenia ligulata is widely used plant in South Asia, mainly India and Pakistan, as a traditional medicine for treatment of urolithiasis.

Aim of the study

To rationalize the Bergenia ligulata use in kidney stones and to explain the underlying mechanisms.

Materials and methods

The crude aqueous-methanolic extract of Bergenia ligulata rhizome (BLR) was studied using in vitro and in vivo methods.

Results

BLR inhibited calcium oxalate (CaC₂O₄) crystal aggregation as well as crystal formation in the metastable solutions and exhibited antioxidant effect against 1,1-diphenyl-2-picrylhydrazyl free radical and lipid peroxidation in the in vitro. BLR caused diuresis in rats accompanied by a saluretic effect. In an animal model of urolithiasis, developed in male Wistar rats by adding 0.75% ethylene glycol (EG) in drinking water, BLR (5–10 mg/kg) prevented CaC₂O₄ crystal deposition in the renal tubules. The lithogenic treatment caused polyuria, weight loss, impairment of renal function and oxidative stress, manifested as increased malondialdehyde and protein carbonyl contents, depleted reduced glutathione and decreased antioxidant enzyme activities of the kidneys, which were prevented by BLR. Unlike the untreated animals, EG intake did not cause excessive hyperoxaluria and hypocalciuria in BLR treated groups and there was a significant increase in the urinary Mg²⁺, instead of a slight decrease.

Conclusions

These data indicate the antiurolithic activity in Bergenia ligulata mediated possibly through CaC₂O₄ crystal inhibition, diuretic, hypermagneseuric and antioxidant effects and this study rationalizes its medicinal use in urolithiasis.     

Influence of processing on pharmacokinetic of typical constituents in radix polygoni multiflori after oral administration by LC–ESI–MS/MS

Ethnopharmacological relevance

The processed radix polygoni multiflori (P-RPM) are produced from the raw radix polygoni multiflori (R-RPM) steamed with black bean juice, but the two traditional Chinese medicines are used to treat the different diseases in clinic. In order to clarify the influence of processing on pharmacological properties of radix polygoni multiflori, an investigation was carried out to compare the pharmacokinetics of typical constituents after oral administration of P-RPM and R-RPM extracts

Materials and methods

A simple, rapid and sensitive high performance liquid chromatography–tandem mass spectroscopy (LC–MS/MS) was developed and validated for the simultaneous determination of gallic acid, polydatin, 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside (PM-SG), resveratrol, and emodin in rat plasma. Male Sprague-Dawley rats were orally administered the two extracts with approximately the same dosage.

Results

It was found that gallic acid was distributed as opened one-compartment model while polydatin, PM-SG and emodin were fitted to an open two-compartment model after oral administration of raw and processed radix polygoni multiflori extract. Cmax and AUC of gallic acid were increased (P<0.01), but C_max and AUC of PM-SG were descreased (P<0.05). AUC of polydatin and emodin were similar with that of PM-SG. However, resveratrol was not detected in plasma collected at certain intervals following oral administration of the two extracts.

Conclusions

These results indicate that influence of the processing could improve the bioavailability of gallic acid and reduce the absorption of PM-SG, polydatin and emodin in rats. The LC–MS/MS method could be used to evaluate the effect of processing on pharmacokinetic of typical constituents in radix polygoni multiflori after oral administration.     

The in vitro antiviral property of Azadirachta indica polysaccharides for poliovirus

Ethnopharmacological relevance

Azadirachta indica A. Juss, popularly known as neem, has been extensively used in Ayurvedic medicine by Indian population for over 2000 years. It is used traditionally for the healing of various diseases. Natural products and their derivatives provide an excellent source for new anti-viral drugs.

Aim of the study

The present study aims at evaluating the activity of two polysaccharides (P1 and P2) isolated from the leaves of Azadirachta indica and their chemical sulfated derivatives (P1S and P2S) against poliovirus type 1 (PV-1).

Materials and methods

The cytotoxicity of the compounds was analyzed by MTT and the antiviral effect was determined by plaque reduction assay in different protocols.

Results

The polysaccharides did not show any cytotoxic effects on HEp-2 cells at the highest tested concentration (200 μg/ml) and exhibited significant antiviral activity with inhibitory concentrations (IC₅₀) of 80 μg/ml, 37.5 μg/ml, 77.5 μg/ml, and 12.1 μg/ml for P1, P1S, P2 and P2S, respectively, and the selectivity indexes (SI) ranged from 18 to 131.9. The compounds demonstrated better inhibitory effect when added concomitantly with the virus infection with a dose-dependent curve inhibition. Lesser effect was observed when the compounds were added after viral infection and the least effect at pre-treatment.

Conclusions

We suggested that the polysaccharides obtained from Azadirachta indica act against PV-1 by inhibiting the initial stage of viral replication. Importantly, original polysaccharides showed better virucidal effect than their sulfated derivatives at all tested concentrations. This study provides a scientific basis for the past and present ethnomedical uses of this plant.     

A UPLC–MS/MS method for in vivo and in vitro pharmacokinetic studies of psoralenoside,isopsoralenoside, psoralen and isopsoralen from Psoralea corylifolia extract

Ethnopharmacological relevance

The dried fruit of Psoralea corylifolia L. has been used to prevent and treat vitiligo, osteoporosis, arthralgia and asthma in Traditional Chinese Medicine for some 1600 years. Psoralen (P), isopsoralen (IP), psoralenoside (PO) and isopsoralenoside (IPO) are the major coumarins and coumarin-related benzofuran glycosides in Psoraleae Fructus, which have been reported to show estrogen-like activity, osteoblastic proliferation accelerating activity, antitumor effects and antibacterial activity. The first aim of this study is to develop a rapid, sensitive and selective ultra performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) approach for simultaneous determination of PO, IPO, P and IP in rat plasma and samples collected from in vitro incubation experiments. The second aim is to investigate the pharmacokinetic properties of PO, IPO, P and IP after oral administration of Psoralea corylifolia extract (PCE) to rats. The third aim is to confirm the biotransformation of PO to P or IPO to IP under gastrointestinal conditions.

Materials and methods

A UPLC–MS/MS method with a C18 column and a mobile phase of methanol-0.1% aqueous formic acid was validated according to the criteria in FDA guidelines about bioanalytical method, which was developed to investigate the pharmacokinetic behavior of PO, IPO, P and IP from PCE and the metabolic pathways of PO to P or IPO to IP.

Results

The criteria for establishment of a new UPLC–MS/MS method including selectivity, linearity, accuracy, precision, extraction recovery, matrix effect and stability were validated. This method was successfully applied to the quantitative determination of PO, IPO, P and IP in biological samples collected from both in vitro incubations and in vivo rat experiments. After oral administration of PCE to rat, pharmacokinetic parameters of these four compounds indicated that in vivo biotransformation may occur between PO and P or IPO and IP. Purified benzofuran glycosides fraction (PBGF), containing only PO and IPO, was orally administered to rats to further confirm the biotransformation of PO to P or IPO to IP under gastrointestinal conditions. An in vitro incubation study elucidated that PO and IPO were metabolized to P and IP by intestinal microflora through de-glucosylation.

Conclusions

This paper developed a rapid, sensitive and selective UPLC–MS/MS method for simultaneous determination of PO, IPO, P and IP from PCE in biological samples, and investigated on their comprehensive in vivo and in vitro pharmacokinetic studies. These obtained results showed that the metabolism by intestinal bacteria plays an important role in pharmacological effects of orally administered PCE.     

A bioactivity-guided study on the anti-diarrheal activity of Polygonum chinense Linn

Ethnopharmacological relevance

Polygonum chinense Linn., a folk medicine, has long been used for the treatment of diarrhea and enteritis in southwestern China. However, the components responsible for its anti-diarrheal activity are still poorly understood.

Aim of the study

To determine anti-diarrheal activities of Polygonum chinense L. and to identify its active components through bioactivity-guided isolation technique.

Materials and methods

Animals were orally administered with the extract of Polygonum chinense L. The anti-diarrheal effects of 75% ethanol extract, four fractions with different polarities from 75% ethanol extract, different eluates collected from Diaion HP-20 macroporous resin chromatography, ellagic acid and corilagin, were examined based on mouse models of castor oil- and magnesium sulfate-induced diarrhea.

Results

The results showed that the 75% ethanol extract of Polygonum chinense L. exhibited significant anti-diarrheal activities in a dose-dependent manner in two mouse models. Through in vivo bioactivity-guided fractionation processes, n-butanol and aqueous fractions were found to exhibit prominent anti-diarrheal activities, and two major compounds, ellagic acid and corilagin, from these active fractions were found to possess anti-diarrheal effects.

Conclusion

Present study provides evidence of the utilization of Polygonum chinense L. for diarrhea, and ellagic acid and corilagin are two components contributing to the anti-diarrheal effect.     

1H NMR-based metabonomics study of the urinary biochemical changes in Kansui treated rat

Ethnopharmacological relevance

The dried root of Kansui (Euphorbia kansui L.) is a commonly used and effective traditional Chinese medicine (TCM).

Aim of the study

We combined the urinary metabolites alteration and traditional assays of Kansui-induced rats to discuss the mechanism of toxicity of Kansui.

Materials and methods

The Sprague–Dawley rats were dosed with 7.875 g Kansui/kg weight and 15.75 g Kansui/kg weight. Urine samples were collected at day −1 (before treatment), and days 7, 14 and 21 for NMR analysis. Plasma and liver and kidney tissues were collected at day 14 for biochemical assays and histopathological examination, respectively.

Results

The metabonome of rats treated with Kansui differed markedly from that of the controls. This was confirmed by the histopathology of liver and kidney tissue and clinical biochemistry analysis. The toxicity of Kansui accumulated with dosing time, and persisted even when treatment was stopped. The corresponding biochemical pathways alterations included inhibited TCA cycle, increased anaerobic glycolysis, and perturbed amino acids metabolism.

Conclusion

The biochemical pathways disorder conjunction with histopathology changes provides new clues to evaluate the toxicity of Kansui from a systematic and holistic view.     

In vitro and in vivo hepatoprotective and antioxidant activity of ethanolic extract from Meconopsis integrifolia (Maxim.) Franch

Ethnopharmacological relevance

Meconopsis integrifolia (Maxim.) Franch is a high mountain endemic species used as a traditional Tibetan and Mongolian herb to treat hepatitis, pneumonia, and edema. This study aims to investigate the hepatoprotective and antioxidant effects of Meconopsis integrifolia ethanolic extract (MIE) in vitro and in vivo.

Materials and methods

The in vitro antioxidant property of MIE was investigated by employing various established systems. Rats with carbon tetrachloride (CCl₄)-induced liver injury were used to assess the hepatoprotective and antioxidant effect of MIE in vivo. The level or activity of alkaline phosphatase (ALP), glutamate pyruvate transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB) in the blood serum and thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) in the liver and kidney of the rats were assayed using standard procedures.

Results

MIE exhibited strong antioxidant ability in vitro. In the rats with CCl₄-induced liver injury, the groups treated with MIE and silymarin showed significantly lower levels of ALT, AST, ALP, and TB. MIE demonstrated good antioxidant activities in both the liver and kidney of the rats in vivo.

Conclusions

MIE exhibits excellent hepatoprotective effects and antioxidant activities in vitro and in vivo, supporting the traditional use of Meconopsis integrifolia in the treatment of hepatitis.     

Cytotoxicity and antibacterial activity of Lindera strychnifolia essential oils and extracts

Aim of the study

Lindera strychnifolia (LS) is widely used in traditional Chinese medicine. In the present study, we investigated cytotoxicity and antibacterial activity of essential oils and various fractions of ethanol extract of LS to explore the active components of LS and their pharmacological effects.

Materials and methods

The in vitro cytotoxicities of essential oils and various solvent fractions of LS on three human cancer cell lines (A549, HeLa and Hep G2) and a non-cancerous cell line (HUVEC) were examined using a modified MTT assay. And by using agar disc diffusion and broth microdilution methods, the antibacterial activity of these samples was evaluated against 10 bacteria including 5 clinically isolated strains. The compositions of the essential oils from the leaves and roots of LS were also analyzed by GC and GC–MS.

Results

The leaf oil showed the strongest cytotoxicity on the cancer cell lines tested with the IC₅₀ values ranged from 22 to 24 μg/ml after 24 h of treatment. The most sensitive microbial strain to all the samples was Staphylococcus aureus ATCC 25923.

Conclusions

Our results showed that the essential oils of LS exhibited greater cytotoxicity and antibacterial activity than the solvent fractions of ethanol extract of LS.