Inhibitory effects of Chelidonium majus extract on atopic dermatitis-like skin lesions in NC/Nga mice

Aim of the study

Chelidonium majus (CM) has traditionally been used for treatment of various inflammatory diseases including atopic dermatitis (AD). However its action on atopic dermatitis (AD) is unclear. Therefore, we investigated the effect of CM on AD using NC/Nga mice as an AD model.

Materials and methods

The effect of CM on 1-chloro-2,4-dinitrobenzene (DNCB) induced NC/Nga mice was evaluated by examining skin symptom severity, itching behavior, ear thickness, levels of serum immunoglobulin E (IgE), tumor necrosis factor-α (TNF-α), and interlukin-4 (IL-4), skin histology.

Results

The CM significantly reduced the total clinical severity score, itching behavior, ear thickness and the level of serum IgE in AD mouse model. CM not only decreased TNF-α but also IL-4.

Conclusion

These results suggest that CM may be a potential therapeutic modality for AD.     

Antitumor effects and chemical compositions of Eupolyphaga sinensis Walker ethanol extract

Ethnopharmacological relevance

Eupolyphaga sinensis Walker popularly known as “preferred drug to regulate blood flow” are traditionally used in folk medicine in the treatment of ecchymoma, posttraumatic wound, hepatic fibrosis and tumor.

Aim of the study

To characterize chemical compositions and to evaluate the antitumor and immunomodulatory of Eupolyphaga sinensis Walker ethanol extract (ESEE) in hepatocarcinoma H₂₂ bearing mice.

Materials and methods

ESEE was obtained by ethanol reflux extraction and analyzed by gas chromatography–mass spectrometry (GC–MS) after methylation. ICR mice were treated with ESEE for 14 consecutive days at doses of 31 mg/kg (low-dose), 62 mg/kg (mid-dose) and 124 mg/kg (high-dose) after H₂₂ tumor cells were implanted. At the end of the experiments, the tumor weight of each mouse was measured. Levels of serum TNF-α and IFN-γ was assayed by ELISA. Protein expressions of Bax, Bcl-2 and caspases-3 were detected by immunohistochemistry.

Results

Chemical analysis revealed the presence of 6 components that account for 97.55% of fatty acids, indicating the occurrence of saturated and polyunsaturated fatty acids. Oral administration of ESEE could inhibit tumor growth, promote Th1 type cytokine productions (TNF-α and IFN-γ) and induce apoptosis of hepatocarcinoma via increase of Bax/Bcl-2 ratio and activation of caspases-3. Oral administration of ESEE in a dosage of 6.2 g/kg did not lead to toxic effects in mice.

Conclusions

ESEE was effective in inhibiting tumor growth in vivo and could also serve as immunoadjuvant for tumor therapy.     

Parkinsonia aculeata aqueous extract fraction: biochemical studies in alloxan-induced diabetic rats

The antidiabetic effect of Parkinsonia aculeata water soluble fraction (WSF) made of aerial parts of the plant (leaves and flowers) was investigated in alloxan diabetic rats. Its effect was compared with that of insulin (positive control). The physico-metabolic parameters measured were: body weight, food and liquid intake, urinary volume, hepatic glycogen, serum glucose, total cholesterol, HDL-cholesterol, triglycerides, urinary glucose and urea, and the weight of epididymal adipose tissue, liver, kidneys and the skeletal muscles (soleus and extensor digitorum longus). Oral administration of WSF (125 or 250 mg/kg) for 16 days exhibited a significant reduction in serum and urinary glucose, urinary urea, total cholesterol, HDL-cholesterol and triglycerides in alloxan diabetic rats. An improvement of hepatic glycogen, a decrease of liquid and food intake, and a significantly positive actions in the weight of skeletal muscles (soleus and extensor digitorum longus) and kidneys were also observed, but just diabetic group treated with WSF at a dose of 125 mg/kg showed significant reduction in urinary volume, body weight, an improvement of epididymal adipose tissue and a positive action in liver weight. The effects of WSF on the physico-metabolic parameters was comparable to those observed in diabetic insulin treated group. The results of this work suggest that P. aculeate may have new clinical significant choice in diabetes mellitus illness, and could explain the basis for its traditional use to manage diabetes-related complications by rural community of northeast of Brazil.     

Chemical compositions and anti-influenza activities of essential oils from Mosla dianthera

Ethnopharmacological relevance

Mosla dianthera as an aromatic herb is used in folk medicine for the treatment of cough, colds, fever, bronchitis, nasal congestion and headache.

Aim of the study

To characterize chemical compositions and to evaluate the anti-influenza effects of essential oils of M. dianthera (MDEO) in influenza virus A (IVA) infected mice.

Materials and methods

MDEO was obtained by hydrodistillation and analysed by gas chromatography-mass spectrometry (GC-MS). ICR mice were treated with MDEO for 5 consecutive days at doses of 90-360 mg/kg after post-infected. Levels of Serum IL-4 and IFN-γ were assayed by ELISA. Levels of MOD, SOD, TAOC and GSH-Px in lung tissue were determined by colorimetric method.

Results

GC-MS analysis revealed the presence of 29 components that account for 97.74% of phenolic sesquiterpenes and aromatic compounds. The major compounds were elemicin (16.51%), thymol (14.77%), β-caryophyllene (14.49%), iso-elemicin (9.22%), asarone (6.09%) and α-caryophyllene (5.26%). It had significant effects on decreasing lung viral titers, inhibiting pneumonia, reducing levels of serum IFN-γ and IL-4, and enhancing antioxidant activity in the lung tissue of IVA infected mice.

Conclusions

MPE could exhibit therapeutical effects in IVA infected mice as a suppressor of IVA replication and inflammatory mediators and a promoter of antioxidant potentials. Therefore, MDEO could provide a safe and effective therapeutic candidate for treatment of influenza and its subsequent viral pneumonia.     

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.     

Analgesic and anti-inflammatory effects of Pistacia integerrima extracts in mice

Aim of study

Extracts of Pistacia integerrima galls have been dispensed by Traditional Practitioners of Subcontinent for chest diseases as well as for aches and pains in the body. This study was planned to evaluate the possible analgesic and antiinflammatory effects of Pistacia integerrima extracts.

Materials and methods

Analgesia was determined using acetic acid induced abdominal constriction and formalin induced paw licking in mice. Antinociceptive effect was observed by thermally induced algesia in mice.

Results

Pistacia integerrima leaves extracts showed significant response against chemically induced pain (P < 0.001) whereas galls extracts had highly significant protection (P < 0.0001) in a dose dependent manner. In thermally induced algesia, Pistacia integerrima galls extracts 200 mg/kg (p.o.), showed significant (P < 0.05) response but less than pentazocine and diclofenac, positive references. The extracts of Pistacia integerrima 50–200 mg/kg (p.o.) had modest activity against hind paw acute and chronic inflammation induced by formalin (P < 0.01).

Conclusion

These results demonstrate that Pistacia integerrima extracts have antinociceptive and analgesic effects and no apparent acute toxicity on oral administration.     

Antiarrhythmic effects of dehydroevodiamine in isolated human myocardium and cardiomyocytes

Ethnopharmacological relevance

Dehydroevodiamine alkaloid (DeHE), a bioactive component of the Chinese herbal medicine Wu-Chu-Yu (Evodiae frutus), exerted antiarrhythmic effect in guinea-pig ventricular myocytes. We further characterize the electromechanical effects of DeHE in the human atrial and ventricular tissues obtained from hearts of patients undergoing corrective cardiac surgery or heart transplantation.

Materials and methods

The transmembrane potentials of human myocardia were recorded with a traditional microelectrode technique while sarcolemmal Na⁺ and Ca²⁺ currents in single human cardiomyocytes were measured by a whole-cell patch-clamp technique. The intracellular pH (pH_i) and Na⁺–H⁺ exchanger (NHE) activity were determined using BCECF-fluorescence in human atria.

Results

In human atria, DeHE (0.1–0.3 μM) depressed upstroke velocity, amplitude of action potential, and contractile force, both in slow and fast response action potential. Moreover, the similar depressant effects of DeHE were found in human ventricular myocardium. Both in isolated human atrial and ventricular myocytes, DeHE (0.1–1 μM) reversibly, concentration-dependently decreased the Na⁺ and Ca²⁺currents. Moreover, DeHE (0.1 and 0.3 μM) suppressed delayed afterdepolarizations and aftercontractions, induced by epinephrine and high [Ca²⁺]_o in atria. In human ventricular myocardium, the strophanthidin-induced triggered activities were attenuated by pretreating DeHE (0.3 μM). The resting pH_i and NHE activity were also significantly increased by DeHE (0.1–0.3 μM).

Conclusions

We concluded for the first time that, in the human hearts, DeHE could antagonize triggered arrhythmias induced by cardiotonic agents through a general reduction of the Na⁺ and Ca²⁺ inward currents, while increase of resting pH_i and NHE activity.     

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.     

Gut and airways relaxant effects of Carum roxburghianum

Ethnopharmacological relevance

Carum roxburghianum is traditionally used in hyperactive gastrointestinal and respiratory disorders. The present study was carried out to investigate the possible gut and airways relaxant potential of Carum roxburghianum to rationalize its folk uses.

Materials and methods

Crude extract of Carum roxburghianum (Cr.Cr) was studied in in vivo and in vitro techniques.

Results

Cr.Cr exhibited protective effect against castor oil-induced diarrhea in mice at 100–1000 mg/kg. In rabbit jejunum preparations, Cr.Cr (0.03–3.0 mg/mL) caused relaxation of spontaneous and K⁺ (80 mM)-induced contractions at similar concentrations, like papaverine. Pretreatment of tissues with Cr.Cr (0.1–1.0 mg/mL) shifted Ca⁺⁺ concentration–response curves (CRCs) to right, like verapamil. Cr.Cr (0.03 and 0.1 mg/mL) caused leftward shift of isoprenaline-induced inhibitory CRCs, similar to papaverine. In isolated guinea-pig ileum, Cr.Cr (0.01 and 0.03 mg/mL) produced rightward parallel shift of acetylcholine-curves, like atropine. Cr.Cr (1.0–30 mg/kg) caused suppression of carbachol (CCh, 100 μg/kg)-induced increase in inspiratory pressure of anaesthetized rats. In guinea-pig trachea, Cr.Cr (0.03–1.0 mg/mL) relaxed CCh and high K⁺-induced contractions, shifted isoprenaline-induced inhibitory CRCs to left at 0.1 and 0.3 mg/mL and CCh-curves parallel to right (0.01 and 0.03 mg/mL). Cr.Cr did not cause any mortality of mice up to 10 g/kg dose.

Conclusion

These results indicate that Carum roxburghianum possess combination of antidiarrheal, antispasmodic and bronchodilatory effects, which provides pharmacological basis to its traditional use in the disorders of gut and airways hyperactivity, like diarrhea, colic and asthma.     

Pharmacokinetics and tissue distribution of resveratrol,emodin and their metabolites after intake of Polygonum cuspidatum in rats

Ethnopharmacological relevance

The rhizome of Polygonum cuspidatum SIEB. et ZUCC. (Polygonaceae, PC), a widely used Chinese medicine, is commonly prescribed for the treatments of amenorrhea, arthralgia, jaundice, abscess, scald and bruises.

Aim of the study

PC contains various polyphenols including stilbenes, anthraquinones and flavonoids. This study investigated the pharmacokinetics and tissue distribution of emodin and resveratrol in PC.

Material and methods

Male Sprague-Dawley rats were orally administered PC (2 and 4 g/kg) and blood samples were withdrawn at the designed time points via cardiopuncture. Moreover, after 7-dose administrations of PC (4 g/kg), brain, liver, lung, kidney and heart were collected. The concentrations of resveratrol and emodin in the plasma and tissues were assayed by HPLC before and after hydrolysis with β-glucuronidase and sulfatase.

Results

The glucuronides/sulfates of emodin and resveratrol were exclusively present in the plasma. In liver, kidney, lung and heart, the glucuronides/sulfates of resveratrol were the major forms. For emodin, its glucuronides/sulfates were the major forms in kidney and lung, whereas considerable concentration of emodin free form was found in liver. Neither free forms nor conjugated metabolites of resveratrol and emodin were detected in brain.

Conclusion

The sulfates/glucuronides of resveratrol and emodin were the major forms in circulation and most assayed organs after oral intake of PC. However, the free form of emodin was predominant in liver.     

Effect of Vaccinium bracteatum Thunb. leaves extract on blood glucose and plasma lipid levels in streptozotocin-induced diabetic mice

Aim of the study

To investigate the hypoglycemic effects of Vaccinium bracteatum Thunb. leaves (VBTL) extract in streptozotocin-induced diabetic mice.

Materials and methods

After administration of VBTL extract for 4 weeks, the body weight, organ weight, blood glucose (BG), insulin and plasma lipid levels of streptozotocin-induced diabetic mice were measured.

Results

Body weights of diabetic mice treated with VBTL extract were partly recovered. The BG levels of AEG (diabetic mice treated with VBTL aqueous extract) were reduced to 91.52 and 85.82% at week 2 and week 4, respectively (P < 0.05), while those of EEG (diabetic mice treated with VBTL ethanolic extract) were reduced slightly (P > 0.05). The insulin levels of AEG and EEG were obviously higher (P < 0.05) than those of MC (diabetic mice in model control group). Comparing with MC, AEG and EEG had significantly lower (P < 0.05) TC or TG levels and similar HDL-cholesterol or LDL-cholesterol levels. In comparison with non-diabetic control mice, AEG had similar plasma lipid levels except higher LDL-cholesterol level, while EEG had higher TC, TG and LDL-cholesterol levels and lower HDL-cholesterol levels.

Conclusions

Both aqueous and ethanolic extract of VBTL possess a potential hypoglycemic effect in streptozotocin-induced diabetic mice.     

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.     

Protective effect of a polyphenolic rich extract from Magnolia officinalis bark on influenza virus-induced pneumonia in mice

Ethnopharmacological relevance

Magnolia officinalis bark is used in traditional Chinese medicine for the treatment of cough, colds, fever, chronic bronchitis and stomach ailments.

Aim of the study

To investigate therapeutic effects of polyphenol rich extract from M. officinalis bark (MPE) in influenza virus A-infected mice, and to provide evidence for the inflammation response and immunomodulatory potential during infection.

Materials and methods

Mice were infected with influenza virus A (IVA) and MPE at doses of 10 and 20 mg/kg were orally administrated daily for 5 days after challenge. The levels of serum L-6 and TNF-α were determined by ELISA while protein expressions of NF-κB and TLR3 were detected by western blotting analysis.

Results

MPE exhibited significant therapeutical effects on reducing levels of serum NO, IL-6 and TNF-α, inhibiting pneumonia, decreasing lung viral titers and sensitizing IVA-induced apoptosis through down-regulation of NF-κB and TLR3 protein expression in the lung tissue of IVA-infected mice.

Conclusions

MPE could exhibit preventive and therapeutical effects on IVA-infected mice as a suppressor of the production of inflammatory mediators, NO and pro-inflammatory cytokines, TNF-α and IL-6. These effects appeared to be mediated, at least in part, by an inhibition of TLR3 and NF-κB activation. Therefore, MPE could provide a safe and effective therapeutic approach for influenza and its subsequent viral pneumonia.     

Pharmacokinetic study of the prokinetic compounds meranzin hydrate and ferulic acid following oral administration of Chaihu-Shugan-San to patients with functional dyspepsia

Aim of the study

The prokinetic activity of ferulic acid derived from Ligusticum chuanxiong hort in the Chaihu-Shugan-San formula has been shown to be similar to Chaihu-Shugan-San, a popular traditional Chinese medicine for treating functional dyspepsia. The effects of meranzin hydrate, a compound isolated from Fructus aurantii in the Chaihu-Shugan-San formula, are unclear, as the pharmacokinetics have never been studied in patients with functional dyspepsia. This study aimed to describe the pharmacokinetics of ferulic acid and merazin hydrate by evaluating the prokinetics induced by Chaihu-Shugan-San and meranzin hydrate.

Materials and methods

Gastric emptying and intestinal transit were measured after oral administration of a single dose of Chaihu-Shugan-San or meranzin hydrate in rats. The tone of rat ileum was selected as direct evidence of the prokinetic activity of meranzin hydrate. Patients with functional dyspepsia were recruited, and meranzin hydrate and ferulic acid were identified by ultra performance liquid chromatography with tandem mass spectrometry in the plasma of patients following a single oral administration of Chaihu-Shugan-San. The resulting pharmacokinetic properties were determined by ultra performance liquid chromatography coupled to photo diode array.

Results

In rats, single doses of Chaihu-Shugan-San (20 g/kg) and meranzin hydrate (28 mg/kg) significantly accelerated gastric emptying and intestinal transit (Chaihu-Shugan-San: 68.9 ± 5.6% and 72.3 ± 4.7%, meranzin hydrate: 72.9 ± 3.8% and 75.2 ± 3.1%) compared with the control (55.45 ± 3.7% and 63.51 ± 5.1%, P < 0.05), showing similar results as cisapride (69.6 ± 4.8% and 71.6 ± 6.3%). Meranzin hydrate (30, 100 μmol/L) directly increased the amplitude of rat ileum compared with the control (P < 0.01). The pharmacokinetics profiles of meranzin hydrate and ferulic acid in patient plasma was fitted with a two-compartment model detected by a simple, rapid and accurate UPLC method. Time to reach peak concentration of meranzin hydrate (0.371 mg/L) and ferulic acid (0.199 mg/L) was 23.57 min and 27.50 min, respectively. The elimination half-life and area under the concentration-time curve from t = 0 to the last time of meranzin hydrate and ferulic acid were 139.53 min and 31.445 μg min/mL and 131.27 min and 14.835 μg min/mL, respectively. The absorption constant and volume of distribution of meranzin hydrate and ferulic acid were 0.185 ± 0.065 min⁻¹ and 3782.89 ± 2686.72 L/kg and 0.524 ± 0.157 min⁻¹ and 11713 ± 7618.68 L/kg, respectively. The experimental results of the pharmacokinetic parameters of meranzin hydrate and ferulic acid indicate that they were absorbed and distributed rapidly.

Conclusions

The pharmacodynamics and pharmacokinetics of prokinetic Chaihu-Shugan-San and its compounds are useful for monitoring Chaihu-Shugan-San formulas in clinical practice and for understanding therapeutic mechanisms.     

The absorption characterization effects and mechanism of Radix Angelicae dahuricae extracts on baicalin in Radix Scutellariae using in vivo and in vitro absorption models

Ethnopharmacological relevance

Angelicae Dahurica(Hoffm.)Benth.&Hook.f.ex Franch.&Sav combined with Scutellaria baicalensis Georgi. has been widely used as herb-pairs in traditional Chinese medicine (TCM) to treat migraine headache and cataract, but the underlying compatibility mechanism of the two herbs remains unknown.

Aim of study

In the present work, we investigated the additive or synergistic effects of absorption behavior of Radix Angelicae dahuricae extracts on baicalin, and the absorption-enhancing mechanism of Radix Angelicae dahuricae extracts on baicalin.

Materials and methods

Total coumarins (Cou) and volatile oil (VO), as the two main components of Radix Angelicae dahuricae, were extracted by supercritical fluid extraction (SFE) further treated with liquid-liquid separation method. The absorption behavior was investigated by applying the everted gut sac technique and in situ single-pass intestinal perfusion method.

Results and conclusions

The results showed that both the Cou and the VO could improve the intestinal absorption of baicalin in vivo, and had synergistic action the enhanced absorption of baicalin. Since verapamil did not affect the P_app and K_a of baicalin significantly, we concluded that the absorption of Baicalin could not be an active transportation in dependent of P-glycoprotein-Mediated efflux systems. Based on intestinal absorption of drug studying was one of the efficacious methods to clarify the compatibility of principles of herb-pairs. The everted gut sac technique and in situ single-pass intestinal perfusion technique model were the effective methods to study the absorption of drug, the application of the animal model to investigating the absorption of herb-drug interactions or other relevant research purposes is envisioned.     

三七总皂苷对小鼠肝脏谷胱甘肽-S-转移酶的抑制作用及其动力学分析

目的:研究三七总皂苷(total saponins of Panax notoginseng,PNS)对小鼠肝脏谷胱甘肽-S-转移酶( glutathione-Stransferase,GST)的抑制作用及其酶动力学.方法:采用差速离心法制备小鼠胞质液酶,用半数效量概率单位法及LineweaverBurk双倒数作图法求得小鼠肝脏GST的米氏常数(Km)、最大反应速度(Vmax)和三七总皂苷对小鼠肝脏GST的半数抑制浓度( IC50)以及判断三七总皂苷对GST的抑制类型和抑制常数(KI,KIS).结果:三七总皂苷对小鼠肝脏GST有抑制作用,其IC50是189.54 mg·L-1;对底物还原型谷胱甘肽(GSH),GST的Km是0.456 3 mmol·L-1,Vmax是476.19 U·mg-1;对底物1-氯-2,4-二硝基苯(CDNB),GST的Km是0.109 7 mmol·L-1,Vmax是400.00 U·mg-1.对底物GSH,三七总皂苷对小鼠肝脏GST属于混合性抑制,其抑制常数KI是0.27 mg·L-1,KIS是0.68 mg·L-1:对底物CDNB,三七总皂苷对小鼠肝脏GST属于混合性抑制,其抑制常数KI是0.21 mg·L-1,KIS是0.66 mg· L-1.结论:三七总皂苷对小鼠肝脏GST的活性有明显抑制作用.     

Anti-influenza virus effects of the aqueous extract from Mosla scabra

Ethnopharmacological relevance

Mosla scabra (Thunb.) C. Y. Wu is a broadly used species in the southeastern China as an antipyretic and antiviral drug for the treatment of colds, fever, inflammation and chronic bronchitis.

Aim of the study

To investigate the anti-influenza virus activities of the aqueous extract from Mosla scabra (AEMS), and to provide evidence for the implication of its immunomodulatory potential for the overall protective effect in lethal murine experimental influenza A infection.

Materials and methods

The anti-influenza virus activities of AEMS or ribavirin were evaluated in embryonated eggs and in a mouse infection model and the effects of AEMS on early immune responses during influenza virus infection were evaluated in a mouse infection model.

Results

At the concentration of 0.3–30.0 mg/ml, AEMS exhibited both preventive and therapeutical effect on embryonated egg. Oral administration of AEMS to mice infected with influenza virus A (IVA) was highly effective in preventing death, inhibiting pneumonia and reducing lung viral titers. It also significantly enhanced IFN-γ, IL-2, IL-4 and IL-5 cytokine-producing splenocytes, increased T-cell subsets like CD4⁺ and CD4⁺/CD8⁺, decreased levels of IL-6 after infection, and provided protective immunity. At a dosage of 4800 mg/kg, almost all treated mice survived, suggesting that AEMS is of low toxicity. However, ribavirin has weaker efficacy compared to AEMS.

Conclusions

These results showed, for the first time, while both AEMS and ribavirin appeared to have similar efficacy against IVA, AEMS playing a role as an immunomodulator and antiviral inhibitor during influenza virus infection, was considered to be less toxic and may warrant further evaluation as a possible agent for the treatment of influenza.