Bronchospasm potentiating effect of methanolic extract of Ficus religiosa fruits in guinea pigs

Ethnopharmacological relevance

The sacred tree Peepal (Ficus religiosa family: Moraceae) has numerous therapeutic utility in folk medicine.

Aim of the study

It has been reported to be used in ethno medical treatment of asthma and also in epilepsy due to its high serotonin content, which has been implicated in pathophysiology of asthma, this led us to carry out the present study.

Materials and methods

The in vivo studies of histamine induced bronchospasm in guinea pigs and in vitro isolated guinea pig tracheal chain and ileum preparation.

Results

Pre-treatment of guinea pigs with ketotifen (1 mg/kg, p.o.) has significantly delayed the onset of histamine aerosol induced pre-convulsive dyspnea, compared with vehicle control (281.8^a ± 11.7 vs. 112.2 ± 9.8). The administration of methanolic extract (125, 250 and 500 mg/kg, p.o.) did not produced any significant effect on latency to develop histamine induced pre-convulsive dyspnea. On the other hand, methanolic extract of the fruits at the doses employed (i.e., 0.5, 1 and 2 mg/ml) has significantly potentiate the EC₅₀ doses of both histamine and acetylcholine in isolated guinea pig tracheal chain and ileum preparation. In addition, HPLC analysis of the methanolic extract showed the presence of high amounts of serotonin (2.89%, w/w).

Conclusions

On the basis of data, it may be concluded that Ficus religiosa fruits have been found to be ineffective against histamine induced bronchospasm in guinea pigs. In addition, methanolic extract of the fruits have shown to potentiate the bronchoconstriction induced by both histamine and acetylcholine on guinea pig tracheal chain preparation.     

Inhibition of airway inflammation by the roots of Angelica decursiva and its constituent,columbianadin

Ethnopharmacological relevance

The roots of Angelica decursiva Fr. Et Sav (Umbelliferae) have been frequently used in traditional medicine as anti-inflammatory, antitussive, analgesic agents and expectorant, especially for treating cough, asthma, bronchitis and upper respiratory tract infections. To establish the scientific rationale for the clinical use of Angelica decursiva and to identify new agents for treating inflammatory lung disorders, pharmacological evaluation of the roots of Angelica decursiva and the isolated constituents was performed.

Methods

In vitro study was carried out using two lung cells, lung epithelial cells (A549) and alveolar macrophages (MH-S). The inflammatory markers such as IL-6 and nitric oxide (NO) for each cell line were examined. For in vivo study, a mouse model of lipopolysaccharide (LPS)-induced acute lung injury was used and the effects on lung inflammation were established by measuring the cell numbers in bronchoalveolar lavage fluid (BALF) and by histological observation.

Results

Water and 70% ethanol extracts of the roots of Angelica decursiva showed considerable inhibitory activity against LPS-induced lung inflammation in mice following oral administration at a dose of 400 mg/kg. Five coumarin derivatives including columbianadin, umbelliferone, umbelliferone 6-carboxylic acid, nodakenin and nodakenetin were isolated. Among the isolated compounds, columbianadin was found to possess strong inhibitory activity against the inflammatory response of IL-1β-treated A549 cells and LPS-treated MH-S cells. Columbianadin was found to inhibit NO production by down-regulation of inducible NO synthase. Moreover, columbianadin was also proved to possess significant inhibitory activity against LPS-induced lung inflammation following oral administration at a dose of 20–60 mg/kg.

Conclusions

The roots of Angelica decursiva were proved to be effective in the treatment of lung inflammation. Columbianadin can be a potential new agent for treating inflammatory lung disorders.     

The root barks of Morus alba and the flavonoid constituents inhibit airway inflammation

Ethnopharmacological relevance

The root barks of Morus alba have been used in traditional medicine as an anti-inflammatory drug, especially for treating lung inflammatory disorders.

Aim of study

To find new alternative agents against airway inflammation and to establish the scientific rationale of the herbal medicine in clinical use, the root barks of Morus alba and its flavonoid constituents were examined for the first time for their pharmacological activity against lung inflammation.

Materials and methods

For in vivo evaluation, an animal model of lipopolysaccharide-induced airway inflammation in mice was used. An inhibitory action against the production of proinflammatory molecules in lung epithelial cells and lung macrophages was examined.

Results

Against lipopolysaccharide-induced airway inflammation, the ethanol extract of the root barks of Morus alba clearly inhibited bronchitis-like symptoms, as determined by TNF-α production, inflammatory cells infiltration and histological observation at 200–400 mg/kg/day by oral administration. In addition, Morus alba and their major flavonoid constituents including kuwanone E, kuwanone G and norartocarpanone significantly inhibited IL-6 production in lung epithelial cells (A549) and NO production in lung macrophages (MH-S).

Conclusions

Taken together, it is concluded that Morus alba and the major prenylated flavonoid constituents have a potential for new agents to control lung inflammation including bronchitis.     

Relaxant effect of 1-butanol fraction from Elaeagnus pungens leaf through inhibiting l-type Ca channel on guinea pig tracheal smooth muscle

Ethnopharmacological relevance

The leaf of Elaeagnus pungens thunb. (Family Elaeagnaceae) has been documented as an effective herb for the treatment of asthma and chronic bronchitis in traditional Chinese medicine. In the past years, only a few of preliminary studies reported the chemical constituents and pharmacology effects of the herb, but their action on the tracheal relaxation has not been investigated.

Aim of the study

To investigate the relaxing effect and mechanism of the extracts from Elaeagnus pungens leaves on guinea pig tracheal smooth muscle and bronchi smooth muscle cells.

Materials and methods

Four fractions of different polarities from Elaeagnus pungens leaves were tested to the tracheal strips on the resting tension or pre-contracted by histamine (20 μM) and acetylcholine (20 μM). Inhibitory effects of the 1-butanol fraction (400 mg/ml) on cumulative histamine and acetylcholine (0.2–20 μM) induced contraction were measured. In order to determine the mediators on the 1-butanol fraction effect, the relaxing effect of the 1-butanol fraction was evaluated in the absence and presence of β-adrenoceptor antagonists (1 μM propranolol), K⁺ channels-blockers (4-aminopyridine (2 mM), tetraethylammonium chloride (5 mM) or glibenclamide (10 μM)), the cyclooxygenase inhibitor (indomethacin, 10 μM), nitric oxide synthase inhibitor (Nω-nitro-l-arginine methyl ester, 100 μM) or l-type Ca²⁺ channel inhibitor (nifedipine, 1 μM). Moreover, [Ca²⁺]_i in bronchi smooth muscle cells was analyzed by measuring the fluorescence intensity with confocal system.

Results

1-Butanol fraction induced the highest relaxant effect among four fractions of different polarities from Elaeagnus pungens leaves, and significantly relaxed the tracheal strip in the concentration-dependent manner on the resting tension and pre-contracted by histamine phosphate and acetylcholine. It also produced an unparallel rightward shift of the cumulative concentration-response curve of histamine or acetylcholine. Furthermore, the relaxant effect of 1-butanol fraction was not affected by propranolol, glibenclamide, tetraethylammonium chloride, 4-aminopyridine, indomethacin and Nω-nitro-l-arginine methyl ester. However, 1-butanol fraction-induced relaxation decreased after adding nifedipine. It also concentration-dependently inhibited CaCl₂-induced contraction in the Ca²⁺-free, 60 mM K⁺-containing solution. Additionally, [Ca²⁺]_i in the BSMCs significantly reduced after administration of the 1-butanol fraction.

Conclusions

The 1-butanol fraction from Elaeagnus pungens leaves resulted in a relaxation in the non-precontracted and pre-contracted tracheal strips. The relaxant effect was not related to K⁺ channels, NO, cGMP or β-adrenoceptors, but related to the inhibition of Ca²⁺ influx through l-type Ca²⁺ channels.     

Anti-histamine effect of Rubia tibetica, used to treat anaphylaxis caused by tick bites in the Pamir Mountains, Afghanistan

Ethnopharmacological relevance

The roots of Rubia tibetica are chewed as an antidote to anaphylaxis caused by bites of the tick Ornithodoros lahorensis by the Wakhi people in Afghanistan.

Aims of the study

To test whether Rubia tibetica possess anti-histamine effect.

Materials and methods

Water and ethanol extracts of roots of Rubia tibetica were tested for anti-histamine effect on the H₁-receptor in the guinea pig ileum assay. Fixed concentrations of plant extract with increasing concentrations of histamine were examined. Mepyramine was used as control.

Results and conclusion

The ethanol extract of Rubia tibetica showed dose-dependent anti-histamine effect, whereas the water extract had little activity. The chewing of Rubia tibetica roots may alleviate the fatal swelling of the tongue during anaphylaxis.     

The effect of Nigella sativa Linn. seed on memory,attention and cognition in healthy human volunteers

Background

Experimental evidences have demonstrated that Nigella sativa Linn. seed (NS) has positive modulation effects on aged rats with memory impairments, prevents against hippocampal pyramidal cell loss and enhances consolidation of recall capability of stored information and spatial memory in rats. NS has neuroprotective, nephroprotective, lung protective, cardioprotective, hepatoprotective activities as established by previous studies on animals. Several clinical trials with NS on human have also demonstrated beneficial effect.

Aim of the study

The present study was designed to investigate the effects of NS on memory, attention and cognition in healthy elderly volunteers. Furthermore, safety profile of NS was assessed during the nine-week study period.

Methods

Forty elderly volunteers were recruited and divided randomly into group A and group B—each consisting of 20 volunteers. The treatment procedure for group A was 500 mg NS capsule twice daily for nine weeks and Group B received placebo instead of NS in the similar manner. All the volunteers were assessed for neuropsychological state and safety profile twice before treatment and after nine weeks. The neuropsychological tests were logical memory test, digit span test, Rey-Osterrieth complex figure test, letter cancellation test, trail making test and stroop test. Safety profile was assessed by measuring biochemical markers of Cardiac (total cholesterol, triglycerides and high density lipoprotein cholesterol, very low density lipoprotein, low density lipoprotein cholesterol, creatine kinase-MB); Liver (aspartate aminotransferase, alanin aminotransferase, alkaline phosphatase, total protein, albumin, bilirubin) and Kidney (creatinine and blood urea nitrogen) through using commercial kits.

Results

There was significant difference (p<0.05) in the score of logical memory test-I and II, total score of digit span, 30 min delayed-recall, percent score in Rey-Osterrieth complex figure test, time taken to complete letter cancellation test, time taken in trail making test-A and test-B, score in part C of stroop test due to ingestion of NS for nine weeks. There were not statistically significant changes (p>0.05) in any of the biochemical markers of cardiac, liver, kidney function during this nine-week study period.

Conclusions

The current study demonstrates the role of NS in enhancing memory, attention and cognition. Therefore, whether NS could be considered as potential food supplement for preventing or slow progressing of Alzheimer disease needs further investigations. However, study with Alzheimer′s patients with large population size for longer period of time is recommended before using NS daily and extensive phytochemical investigations are recommended for novel drug discovery from NS for treating cognitive disorders.     

Anti-inflammatory effect of crude extract and isolated compounds from Baccharis illinita DC in acute skin inflammation

Ethnopharmacologycal relevance

The tea from the leaves of Baccharis illinita DC (Asteraceae family) is commonly used by the population as anti-inflammatory (including topically), protective gastric and anti-infectious. However, no studies have been done with this species to confirm its topical anti-inflammatory action.

Aim

This study evaluated he topical effects of crude extract of leaves (CE) and its active constituents in 12-O-tetradecanoilforbol acetate (TPA)-induced ear oedema.

Methodology

CE and compounds effects were tested in commonly used models of TPA-, arachidonic acid (AA)- and capsaicin-ear oedema. Polymorphonuclear (PMN) cell migration was evaluated by mieloperoxidase and analyzed histologically.

Results

CE (0.1–1 mg/ear) caused a dose-related inhibition of TPA-induced ear oedema and PMN influx similarly to that produced by topical application of the steroidal anti-inflammatory drug dexamethasone. The active constituents of the AcOEt fraction kaurenoic acid, α-spinasterol, oleanolic acid and baurenol also inhibited TPA-induced ear edema. Histological analysis of the ear of CE-treated animals confirmed the reduction of edema and of PMN infiltration. Both CE and the nosteroidal anti-inflammatory drug indomethacin inhibited the AA-induced ear oedema, but did not change capsaicin-induced oedema.

Conclusion

These results indicate that the CE and the active constituents have a topical anti-inflammatory effect and the possible mechanisms for the pharmacological effects are discussed.     

不同炮制方法对广西莪术姜黄素成分及镇痛抗炎的影响

目的:探讨不同炮制方法对广西莪术姜黄素含量及镇痛抗炎作用的影响。方法:HPLC测定广西莪术生品、醋煮品、醋炙品姜黄素的含量;采用小鼠耳廓肿胀法、腹腔染料渗出法研究其抗炎作用;采用热板法、扭体法观察其镇痛作用。结果:广西莪术各炮制品姜黄素的含量为生品>醋炙品>醋煮品;醋制炮制后具有较强的抗炎、镇痛作用。结论:不同炮制方法对广西莪术质量有一定的影响。     

The effects of Nigella sativa on quality of life,disease activity index,and some of inflammatory and oxidative stress factors in patients with ulcerative colitis

The aim of this study was to evaluate the effects of Nigella sativa (NS) supplementation in patients with ulcerative colitis . Two grams of NS powder or placebo were consumed for 6 weeks by 46 patients with active mild to moderate ulcerative colitis. Using valid and common questionnaires of colitis severity and blood sampling, we estimated disease activity index, quality of life, and some of inflammatory and oxidative stress factors at baseline and after 6 weeks of supplementation . NS‐elevated tumor necrosis factor‐alpha and high‐sensitivity‐c‐reactive‐protein as well as reduced malondialdehyde (p = 0.01, p = 0.02, and p = 0.005, respectively) compared with placebo. There was no significant difference between the two groups in serum total antioxidant capacity and nuclear factor kB levels. Total scores of Simple Clinical Colitis Activity Index Questionnaire and Inflammatory Bowel Disease Questionnaire‐9 were not different between the two groups; however, stool frequency score decreased significantly in NS group. Further clinical trials with different pattern of NS administration (the amount of total and divided daily doses, either powder type or standard extracts/oil and different time arrangement) are needed to clarify the vision.     

Inhibitory effect of eupatilin and jaceosidin isolated from Artemisia princeps on carrageenan-induced inflammation in mice

Ethnopharmacological relevance

Artemisia princeps Pampanini (family Asteraceae) is an herbal medicine widely used as a hepatoprotective, antioxidative, anti-inflammatory, and antibacterial agent in Korea, China, and Japan.

Aim of the study

This study aimed to elucidate the anti-inflammatory effect of the main constituents, eupatilin and jaceosidin, isolated from Artemisia princeps.

Materials and methods

We used carrageenan-induced inflammation in an air pouch on the back of mice and carrageenan-induced hind paw edema in rats to determine the anti-inflammatory effects of eupatilin and jaceosidin. Inflammatory makers, such as expression of pro-inflammatory cytokines and cyclooxygenase (COX)-2, and activation of nuclear factor-kappa B (NF-κB), were measured by enzyme-linked immunosorbent assays and immunoblot analyses.

Results

Eupatilin and jaceosidin blocked carrageenan-induced increase in leukocyte number and protein levels in air pouch exudates. Eupatilin and jaceosidin inhibited COX-2 expression and NF-κB activation, and markedly reduced TNF-α, IL-1β, and prostaglandin E2 (PGE₂) levels. They also inhibited hind paw edema induced by carrageenan. Eupatilin and jaceosidin had similar activity.

Conclusions

These findings suggest that eupatilin and jaceosidin may reduce inflammation by inhibiting NF-κB activation, and that Artemisia princeps inhibits inflammation because of these constituents.     

The effect of Salvia divinorum and Mitragyna speciosa extracts,fraction and major constituents on place aversion and place preference in rats

Ethnopharmacological relevance

Consumer use of botanicals has increased despite, in many instances, the paucity of research demonstrating efficacy or identifying liabilities. This research employed the place preference/aversion paradigm to characterize the psychoactive properties of Salvia divinorum extract (10, 30, 100 mg/kg), salvinorin A (0.1, 0.3, 1.0 mg/kg), Mitragyna speciosa MeOH extract (50, 100, 300 mg/kg), Mitragyna speciosa alkaloid-enriched fraction (12.5, 25, 75 mg/kg) and mitragynine (5, 10, 30 mg/kg) in rats.

Material and methods

Following apparatus habituation and baseline preference scores, male Sprague-Dawley rats were given eight counter-balanced drug versus vehicle conditioning trials followed by a preference test conducted under drug-free states. S(+)-amphetamine (1 mg/kg) served as the positive control (in Exp. 2) and haloperidol (0.8, 1.0 mg/kg) served as the negative control in both studies.

Results

Rats displayed place aversion to both Salvia divinorum and salvinorin A that exceeded that of haloperidol. Rats showed place preference to mitragynine that was similar to that of S(+)-amphetamine. This CPP effect was much less pronounced with the Mitragyna speciosa extract and its fraction.

Conclusions

These findings suggest that both botanicals possess liabilities, albeit somewhat different, that warrant caution in their use.     

The analgesic effect of Carum copticum extract and morphine on phasic pain in mice

Pain is a universal complaint, which needs further investigations for new pain relieving agents. Carum copticum (L.) Sprague ex Turrill is a plant in Umbelliferae family, which is mentioned to have some therapeutic effects on headache and joint pains in Iranian traditional literature, but there are not enough scientific reports to prove its effects on pain. So, we conducted to design an experimental clinical trial study to assess and compare the analgesic effect of ethanolic extract of Carum copticum fruit with morphine by using a tail-flick analgesiometer device. Our results indicate that the test drug produced significant increase in tail-flick latency (TFL) during 2h post-drug administration (p<0.05). The peak of the effect was observed at 45min after drug injection, which was comparable to that of 1mg/kg morphine (i.p.). Positive results in this type of analgesiometric test indicate that the antinociceptive action may be of the opoid type. The present study supports the claims of Iranian traditional medicine showing that Carum copticum extract possesses a clear-cut analgesic effect. However, further investigations are required to evaluate the efficacy and safety of this herbal medication in man.     

The effect of total extract of Securigera securidaca L. seeds on serum lipid profiles,antioxidant status,and vascular function in hypercholesterolemic rats

Aim of the study

Seeds of Securigera securidaca are used for the treatment of disorders such as hyperlipidemia, diabetes, and epilepsy in Iranian folk medicine. The possible hypolipidemic and antioxidative effects of hydroalcoholic extract of S. securidaca seeds as well as the effect of the extract on vascular reactivity were investigated in hypercholesterolemic rats.

Materials and methods

High-fat fed wistar rats received orally different doses of the extract for 20 days. At the end of the experiment vein blood and liver were collected to measure the lipid profile, lipid peroxidation, and antioxidative enzyme activities. The thoracic aorta was excised and used for isolated vessel preparation and histological study.

Results

The extract produced significant reductions (p < 0.05) in the level of low-density lipoprotein (LDL) and triglyceride with concomitant reduction in lipid deposition in the liver. The extract also suppressed markedly (p < 0.001) the hypercholesterolemia-induced elevation of malondialdehyde levels both in serum and liver. In hypercholesterolemic rats the endothelium-dependent vasodilatation was improved significantly (p < 0.05) by 100 mg/kg/day of the extract. However, in histological study no atherosclerotic lesion was observed.

Conclusion

These results suggest that S. securidaca seed in addition to decrease lipid levels and peroxidation, is able to improve vascular endothelium-dependent relaxation in hypercholesterolemia.     

南方红豆杉水提物抑制裸鼠A549肺癌移植瘤生长及其机制研究

目的: 研究南方红豆杉水提物对裸鼠A549肺癌移植瘤生长的抑制作用和机制。 方法: 建立荷A549肺癌移植瘤模型,随机分为对照组、低、中、高剂量南方红豆杉水提物实验组,24 h后以等体积生理盐水及药物灌胃,给药7周,每3 d测移植瘤长短径,绘制移植瘤生长曲线,给药7周后处死裸鼠,取瘤组织,计算抑瘤率,采用Real-time PCR及Western blot方法检测mRNA和蛋白水平。 结果: 南方红豆杉水提物各剂量组均有明显抑瘤效果(P<0.05)。与对照组相比,各实验组移植瘤组织中EGFR及Survivin mRNA水平明显下调(P<0.05),VEGF mRNA水平无明显变化。灰度值之比分析显示:各实验组移植瘤组织中EGFR及VEGF蛋白水平均有下调趋势,但差异无统计学意义,Survivin及p-EGFR蛋白水平明显下调(P<0.05)。 结论: 南方红豆杉水提物对血管生成无明显影响,可能通过抑制Survivin蛋白,抑制EGFR磷酸化,起到抑制移植瘤生长的效果。     

Anti-hyperglycemic effect,inhibition of inflammatory cytokines expression,and histopathology profile in streptozotocin-induced diabetic rats treated with Arracacia tolucensis aerial-parts extracts

Ethopharmacological relevance

Arracacia tolucensis is a medicinal plant used in northeast of Mexico as a remedy to treat people with Diabetes mellitus (DM); however, there are no scientific studies that support this information. Thus, we evaluated the anti-hyperglycemic effect of the hexane, ethyl acetate and ethanol extracts from aerial parts in streptozotocin-induced diabetic rats.

Materials and methods

DM was induced in Wistar male rats by single intraperitoneal injection of streptozotocin (STZ 50 mg/kg). After STZ-induction, hyperglycemic rats were treated with all three extracts orally at a single dose (250 mg/kg) each 48 h for 21 days. Glibenclamide (1 mg/kg) was used as a reference drug. The fasting blood glucose levels, the hematic biometry and biochemical profiles, and the inhibition of inflammatory cytokines expression were estimated. Histopathology analysis of pancreas, liver, spleen, and kidney tissue was carried out.

Results

Ours results showed that ethyl acetate extract decreased blood glucose levels significantly (75%, p< 0.05) when compared to diabetic rats and controlled the body weight loss; the lipids level did not change, but the enzyme levels of aspartate aminotransferase and alanine aminotransferase decreased significantly (60.83% and 66.16%, respectively, p< 0.05) and inhibited the expression of inflammatory cytokines,with respect to diabetic rats. Histopathology injury was not observed; by contrast repair of islet of Langerhans was exhibited.

Conclusion

These results validate the use of Arracacia tolucensis as a treatment against DM and suggests it is suitable to continue studies for its safe therapeutic use.     

Antimicrobial interactions of Khoi-San poly-herbal remedies with emphasis on the combination; Agathosma crenulata, Dodonaea viscosa and Eucalyptus globulus

Ethnopharmacological relevance

Plants are often combined in traditional herbal remedies to increase medicinal efficacy, thus this investigation provides some insight into the antimicrobial efficacies of selected combinations.

Aims of the study

The first aim was to scientifically validate antibacterial efficacy of plant mixtures that are traded within peri-urban centres of Cape Town (Western Cape, South Africa). This was followed by an in-depth evaluation of the most antimicrobially active mixture; Agathosma crenulata, Dodonaea viscosa with Eucalyptus globulus.

Materials and methods

Methanol and aqueous extracts of six plant mixtures were screened for antibacterial properties against two Gram-negative and two Gram-positive bacteria using the minimum inhibitory microdilution method. Thereafter, chloroform: methanol (1:1; v/v) extracts, essential oils and aqueous extracts of Agathosma crenulata, Dodonaea viscosa and Eucalyptus globulus were assayed for antimicrobial activity independently and in various combinations. The fractional inhibitory concentration indices (?FIC) were determined for double and triple plant combinations to establish antimicrobial interactions.

Results

From the six plant mixtures prepared by herbalists, a methanol extract derived from combining Agathosma crenulata, Dodonaea viscosa and Eucalyptus globulus showed the best antibacterial activity. The MIC values of 49 μg/ml for Staphylococcus aureus and Bacillus subtilis, and 98 μg/ml for Klebsiella pneumoniae and Escherichia coli were recorded. When Agathosma crenulata, Dodonaea viscosa and Eucalyptus globulus were mixed in various 1:1 combinations, mostly additive and synergistic interactions were noted. The most noteworthy synergistic (ΣFIC value 0.07) 1:1 combinations were observed for the chloroform: methanol extracts of Agathosma crenulata mixed with Eucalyptus globulus against Klebsiella pneumoniae, Staphylococcus aureus and Bacillus subtilis. When combined in a mixture of three plants (1:1:1), enhanced efficacy was evident against most of the pathogens, for both organic and aqueous extracts. The triple combination against Bacillus subtilis demonstrated the greatest synergy (ΣFIC values of 0.03).

Conclusions

The enhanced antimicrobial efficacy and synergistic interactions noted for some of the mixtures, particularly the combination of Agathosma crenulata, Dodonaea viscosa and Eucalyptus globulus support the Western Cape Khoi-San traditional medicinal practices of combining plants for enhanced efficacy.     

The effect of Acorus gramineus on the bioavailabilities and brain concentrations of ginsenosides Rg1, Re and Rb1 after oral administration of Kai-Xin-San preparations in rats

Aim of the study

To investigate the effect of Acorus gramineus (AG), a supposed ‘delivering servant’ according to traditional Chinese medicine principles governing multi-herb formula preparation and formulation, on facilitating the uptake of ginsenosides Rg1, Re and Rb1 to the brain after oral administration of Kai-Xin-San (KXS) preparations.

Materials and methods

Ginseng extracts or KXS with or without AG were administered to rats for pharmacokinetic study and mice for behaviour tests at a dose of 3 g ginseng per kg. The concentrations of ginsenosides in plasma and brain were determined by an LC-MS/MS method, whilst the effects of preparations on spatial learning were evaluated using the Morris water maze test.

Results

KXS in the presence of AG tended to significantly reverse the learning impairment induced by scopolamine. The presence of AG in the KXS formula led to increases in the initial absorption rate and extent of Rg1 and Re in terms of Cmax1 and AUC_0-3 h compared to KXS without AG. Although KXS were found to increase the bioavailabilities and brain concentrations of ginsenosides relative to ginseng extract, the brain-to-plasma AUC_0-12 h ratios appeared not to be affected.

Conclusions

The results suggested that the presence of AG in the KXS formula promoted the initial absorption of ginsenosides Rg1 and Re in the gastrointestinal tract, but unlikely affected the brain-to-plasma AUC ratios.