Analysis of immunological enhancement of immunosuppressed chickens by Chinese herbal extracts

Ethnopharmacological relevance

Radix astragali, Radix codonopis, Herba epimedii and Radix glycyrrizae are 4 plants commonly used in Chinese traditional medicine or veterinary medicine to improve immune functions against chronic diseases in humans and animals.

Aim of the study

We compared immunological enhancement by 4 herbal extracts in clinical healthy chickens or immunosuppressed chickens singly and in combination.

Materials and methods

Water extracts of 4 herbs individually and in different combinations were supplemented in drinking water. Hemagglutination inhibition (HI) antibody titers against Newcastle disease virus (NDV) and H5 avian influenza virus (H5-AIV) after vaccination were measured as indicators to evaluate immunological stimulation across groups supplemented with different herbal extracts. The experiments were conducted in both clinically healthy chickens and chickens with immunosuppression induced by reticuloendotheliosis virus (REV) infection.

Results

In clinically healthy chickens HI antibody titers against NDV and H5-AIV after vaccination were not influenced by supplementation with the herbal extracts of Radix astragali, Radix codonopis, Herba epimedii and Radix glycyrrizae in drinking water. In chicks with REV-induced immunosuppression, however, supplementation of some herbal extracts significantly increased HI antibody titers to NDV and H5-AIV when compared to the immunosuppressed control group (P < 0.01), but the titers were still lower than those in chicks not infected by REV. The 4 herbal mixtures produced the best enhancement among various combinations. The components of the herbal extract were water soluble and treatment by ether had no influence on immunological enhancement. The molecular weights of the active components of the herbal extracts were in the range of 10,000–100,000 Da.

Conclusion

Our results show that the herbal extract supplementation in drinking water can induce an immune stimulation response in immunosuppressed chickens.It suggests that chickens with REV infection-induced immunosuppression could be used as an experiment model for determination of immunological enhancement effects of some herbal components.     

Meta-analysis of Traditional Chinese Medicine in treating functional dyspepsia of liver-stomach disharmony syndrome

Objective

To systematically assess the clinical effectiveness of traditional Chinese medicine (TCM) in the treatment of functional dyspepsia (FD) of liver-stomach disharmony syndrome by meta-analysis.

Methods

Random controlled trials (RCTs) were retrieved from databases, including Pubmed, China national knowledge infrastructure, Wanfang Data, VIP Information, and the Cochrane Library. Trials were selected according to inclusion criteria. The effects of traditional Chinese medicine (TCM) versus prokinetic agents in the treatment of functional dyspepsia (FD) of liver-stomach disharmony syndrome were compared by meta-analysis. RevMan 5.0.24 was used for data analysis. The effective rate was assessed by odds ratios (ORs), and 95% confidence intervals (Cls) were calculated. The cure rate was analyzed by the Peto OR. Simple statistical analysis was chosen to assess the frequency of prescribed Chinese herbs in treating this syndrome.

Results

Thirteen trials were included, involving 1153 patients, and these were of poor methodological quality. Twelve studies mentioned the effective rate and cure rate. TCM therapy showed a better clinical effect rate compared with that with prokinetic agents [OR: 3.2, 95% CI (2.27, 4.51)]. The TCM group also had a better cure rate than that in the group of prokinetic agents [Peto OR: 2.26, 95% CI (1.61, 3.18)]. With regard to the frequency of Chinese herbs used in these 13 trials, Baishao (Radix Paeoniae), Chaihu (Radix Bupleuri), and Gancao (Radix Glycyrrhizae) were mostly prescribed, followed by Xiangfu (Rhizoma Cyperi), Zhishi (Fructus Aurantii Immaturus), Zhiqiao (Fructus Aurantii), Foshou (Citrus medica var.sarcodactylis), and Chenpi (Pericarpium Citri Reticulatae). No serious adverse effects were reported.

Conclusion

TCM therapy shows a superior effective rate and cure rate compared with those in prokinetic agents in the treatment of FD of liver-stomach disharmony syndrome. However, further strictly designed RCTs are required because of the poor quality of included trials.     

A strategy for evaluating antipyretic efficacy of Chinese herbal medicines based on UV spectra fingerprints

Ethnopharmacological relevance

Quality analysis and control of Chinese herbal medicines (CHM) or herbal medicines (HM) are being more and more investigated based on fingerprint analysis, and there are also some researches on correlating fingerprints of CHM to their efficacy. Multi-component analysis methods together with fingerprints are considered potential useful tools to select candidate herbal drugs from extracts of herbs in pharmacological/bio-prospecting investigations.

Aim of the study

To explore a strategy for evaluating efficacy strength of CHM samples based on their spectra fingerprints and validate it.

Methodology

Radix bupleuri (RB), a typical Chinese medicinal herb for relieving exterior syndrome, and Flos lonicerae (FL), Fructus forsythiae (FF), and Radix isatidis (RI) that are widely applied Chinese herbs for heat clearing and detoxifying, were selected as herbal sources. The aqueous extracts, volatile oils and mixtures of the extracts and oils of the four herbs, plus Ibuprofen suspension (IS), Shuanghuanglian oral liquid (SHL), mixture of SHL and the volatile oils of FL and FF, were used for subject samples to do antipyretic experiments on rats. Ultraviolet spectra were used as the spectra fingerprints to represent chemical characteristics of the samples. Principal component analysis (PCA) and canonical correlation analysis (CCA) were adopted as evaluation tools to establish the correlation between pharmacological and spectra data, from which a spectral index for evaluating antipyretic effects of CHM samples was constructed. Furthermore, four compound samples were designed by mixing 50% volatile oils and 50% aqueous extracts of the four herbs with different ratios to validate the strategy.

Results

Efficacy sequence of the 15 calibrating and 4 validating CHM samples, defined by the first canonical correlative variable U₁ of their UV spectra, was consistent with that given by pharmacological experiments.

Conclusions

The strategy proposed in this study could be applied to evaluate efficacy strength of CHM and helpful for screening candidate herbal drugs from different herbs or prepared by different technologies.     

Qiguiyishen decoction reduced the accumulation of extracellular matrix in the kidneys of rats with adriamycin-induced nephropathy

Objective

To investigate the effect of Qiguiyishen decoction (QGYS) on the severity of nephropathy.

Methods

Twenty-four rats were randomly divided into four groups (I, II, III, IV) according to the random number table. Group I as control group did not establish nephropathy model. Groups II, III, and IV were intravenously administered Adriamycin (7.5 mg/kg) through the tail vein to establish nephropathy model. QGYS was prepared with the extracts of Huangqi (Radix Astragali Mongolici), Danggui (Radix Angelicae Sinensis), Niuxi (Radix Achyranthis Bidentatae), and Chuanxiong (Rhizoma Chuanxiong). Group IV was administered QGYS (2 mL · kg⁻¹ · d⁻¹), group III was administered benazepril (10 mL · kg⁻¹ · d⁻¹), and group I, II was administered water (2 mL · kg⁻¹ · d⁻¹) once daily for eight weeks.

Results

QGYS reduced the excretion of urinary protein and N-acetyl-β-D-glucosaminidase and alleviated the accumulation of extracellular matrix (ECM) in renal tissue. Additionally, QGYS effectively regulated the levels of transforming growth factor, tissue inhibitor of matrix metalloproteinase, and matrix metalloproteinases in the kidney of the rats.

Conclusion

QGYS may reduce the accumulation of ECM in the kidneys of rats with Adriamycin-induced nephropathy.     

Three Chinese herbal medicines promote neuroproliferation in vitro, and reverse the effects of chronic mild stress on behavior,the HPA axis,and proliferation of hippocampal precursor cell in vivo

Ethnopharmacological relevance

The present study investigated whether Chinese herbal medicines (CHMs) could reverse the effects of chronic mild stress (CMS) in a depression-like mouse model.

Materials and methods

The effects of three Chinese herbals, Rhizome Chuanxiong, Radix Scutellaria and Radix Phellodendri on promoting neuroproliferation were evaluated in vitro first and followed by in vivo study of mice which were received by an experimental setting of CMS for 14 days. The effects of the three CHMs on depression were evaluated using a behavioral test, named a forced swimming test (FST). The possible anti-depressive mechanisms of these three CHMs, including the modulation of HPA axis and promoting the hippocampal precursor cell proliferation, were evaluated by measuring plasma corticosterone levels and BrdU incorporation.

Results

The in vitro results of MTS assay showed that Rhizome Chuanxiong, Radix Scutellaria and Radix Phellodendri could promote the proliferation of neural stem cells (NSCs) in a concentration-dependent manner. The oral administration of these three CHMs for 14 days reversed not only the elevation of plasma corticosterone levels and body weight loss, but also the decreasing of hippocampal precursor cell proliferation and abnormal behavior in the CMS induced depression-like mouse model.

Conclusion

These results indicated that Rhizome Chuanxiong, Radix Scutellaria and Radix Phellodendri have the potential to ameliorate depression. The possible mechanisms were the inhibition of HPA axis hyperactivity and the increasing of hippocampal precursor cell proliferation. These findings supported the multicomponent and multitargeted approach of Chinese herbal medicine.     

Gas chromatography-mass spectrometry analysis on compounds in volatile oils extracted from Yuan Zhi (Radix Polygalae) and Shi Chang Pu (Acorus Tatarinowii)by supercritical CO2

Objective

To analyze the constituents of volatile oils extracted from Yuan Zhi (Radix Polygalae), Shi Chang Pu (Acorus Tatarinowii), and a mixture of the two herbs.

Methods

The volatile oils were extracted using supercritical fluid extraction (SFE) with CO₂, and the constituents of the volatile oil extracts were analyzed by gas chromatography-mass spectrometry (GC-MS). The relative content of each component was calculated using peak area normalization.

Results

The optimized SFE conditions were 45 MPa at 35°C for 2 h. Twenty-four compounds were identified in the extract from the Yuan Zhi (Radix Polygalae) and Shi Chang Pu (Acorus Tatarinowii) mixture, and six of these had relative contents >1. These compounds were 1,2-dimethoxy-4-(2-propenyl)-benzene; 1,2,3-trimethoxy-5-(2-propenyl)-benzene; β-asarone; (Z, Z) 9,12-octadecadienoic acid; (Z) 6-octadecenoic acid; and ethyl oleate. Combination of the herbs increased the number of pharmacologically active substances in the extract and decreased the number of compounds with one benzene ring compared with the extracts from the individual herbs.

Conclusion

These results indicate there is a synergistic relationship among the compounds in these herbs.     

Literature-based analysis on relationship of symptoms,drugs and therapies in treatment of intestinal diseases

Objective

To evaluate clinical articles published in the past 30 years using the Traditional Chinese Medicine (TCM) theory of the lung being connected with large intestine to treat intestinal diseases. We also analyzed the relationship between symptoms, drugs and therapies with data-excavating technology to aid management.

Methods

After retrieving relevant clinical articles, we set up a database, used Microsoft Structured Query Language Server 2005 Analysis Services as a data-excavating tool, and applied the association rule to study the relationship between the symptoms, drugs and therapies of intestinal diseases.

Results

The key symptoms of dyschesia, constipation, abdominal fullness, fatigue and pale tongue could be treated with Kuxingren (Semen Armeniacae Amarum), Huangqi (Radix Astragali Mongolici) and Gualou (Fructus et Semen Trichosanthis) to invigorate Qi and moisten the intestine. Among these agents, Kuxingren (Semen Armeniacae Amarum) was used most frequently. Clearing Fu-organs was the most prevalent therapy for abdominal fullness, dyschesia, constipation and red tongue. Clearing Fu-organs could be achieved with Kuxingren (Semen Armeniacae Amarum) and Gualou (Fructus et Semen Trichosanthis), whereas Qi could be invigorated using Huangqi (Radix Astragali Mongolici), Gancao (Radix Glycyrrhizae), Baizhu (Rhizoma Atractylodis Macrocephalae) and Kuxingren (Semen Armeniacae Amarum). Moistening the intestine was possible with Kuxingren (Semen Armeniacae Amarum), Huomaren (Fructus Cannabis) and Jiegeng (Radix Platycodi). Also, moistening the lungs was done with Kuxingren (Semen Armeniacae Amarum), ventilating the lungs with Kuxingren (Semen Armeniacae Amarum) and Gualou (Fructus et Semen Trichosanthis), and nourishing the lungs with Huangqi (Radix Astragali Mongolici), Gancao (Radix Glycyrrhizae) and Kuxingren (Semen Armeniacae Amarum). These data demonstrated that Kuxingren (Semen Armeniacae Amarum) was a key agent.

Conclusion

Our analyses of the literature showed clear relationships between symptoms (constipation, dyschesia, abdominal fullness), drugs [Gualou (Fructus et Semen Trichosanthis), Kuxingren (Semen Armeniacae Amarum), Huangqi (Radix Astragali Mongolici)] and therapies (moistening the intestine, clearing Fu-organs, invigorating Qi, ventilating the lungs).     

Traditional Chinese medicine for atopic eczema: PentaHerbs formula suppresses inflammatory mediators release from mast cells

Background

PentaHerbs formula (PHF) containing Cortex Moutan, root bark of Paeonia suffruticosa Andr. (Ranunculaceae), Cortex Phellodendri, bark of Phellodendron chinensis Schneid. (Rutaceae), Flos Lonicerae, flower of Lonicera japonica Thunb. (Capri-foliaceae), Herba Menthae, aerial part of Mentha haplocalyx Briq. (Labiatae) and Rhizoma Atractylodis, rhizome of Atractylodes lancea (Thunb.) DC. (Compositae) at the ratio of 2:2:2:1:2 was useful in the management of eczema.

Aim of the study

Since the mechanism of action of PHF is not known, we aimed to investigate the actions of PHF on mast cell activation.

Materials and methods

Effects of aqueous extracts of PHF and individual component herb on mediator release from rat peritoneal mast cells (RPMCs) and cytokine production from HMC-1 were investigated.

Results

PHF, Cortex Moutan and Herba Menthae significantly attenuated histamine release and prostaglandin D₂ synthesis from RPMC activated by anti-IgE and compound 48/80 (p < 0.05). While Flos Lonicerae and Rhizoma Atractylodis suppressed only mediator release from compound 48/80 activated RPMC, Cortex Phellodendri potentiated only anti-IgE induced mediator release (p < 0.05). However, with the exception of Cortex Moutan, PHF and the other four component herbs failed to affect cytokine production in HMC-1.

Conclusions

Although individual herbs demonstrated different modulating effects on mast cells, inhibition of inflammatory mediator release from mast cells would contribute to the therapeutic efficacy of PHF.     

The influence of compatibility of traditional Chinese medicine on the pharmacokinetic of main components in Fructus Aurantii

Ethnopharmacological relevance

Fructus Aurantii is one of the commonly used traditional Chinese medicines and the compatibility of Fructus Aurantii, Radix et Rhizoma Rhei and Semen Crotonis Pulveratum were the main components in a Chinese traditional patent medicine Weichang'an pill. Naringin and neohesperidin are two main flavonoid glycosides in the extract of Fructus Aurantii. The pharmacokinetics of naringin and neohesperidin, as the main marker constituents were analysis by a simple and accurate method.

Materials and Methods

In the present study, pharmacokinetic differences of two flavonoid glycosides were detected after oral administration of the extract of single herb and different compatibility of Fructus Aurantii, Radix et Rhizoma Rhei and Semen Crotonis Pulveratum which at doses of approximately 700 mg/kg naringin and 300 mg/kg neohesperidin.

Results

It indicated that the pharmacokinetic process of naringin and neohesperidin in four groups were demonstrated bimodal phenomenon after oral administration. Comparing to pharmacokinetic parameters of the single herbs administration, there were no significant difference after the compatibility of Fructus Aurantii and Radix et Rhizoma Rhei. However, the absorption of two flavonoid glycosides was increased dramatically after the compatibility of Fructus Aurantii or Semen Crotonis Pulveratum. The same results were attained after co-administration of the extract of three herbs.

Conclusion

Some components in the extract of Semen Crotonis Pulveratum promoted the absorption of naringin and neohesperidin.     

Ethyl acetate fraction of Radix rubiae inhibits cell growth and promotes terminal differentiation in cultured human keratinocytes

Ethnopharmacological relevance

In Chinese medicine practice, Radix rubiae, the dry root of Rubia cordifolia L. is commonly used for the treatment of psoriasis.

Aim of the study

Psoriasis is a chronic inflammatory skin disorder characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes. Our previous studies identified Radix rubiae to have potent antiproliferative action on cultured HaCaT keratinocytes and to induce keratinocyte differentiation in mouse tail model. The present study aimed to investigate whether Radix rubiae could also induce terminal differentiation in cultured human keratinocytes.

Methods and results

The cornified envelope (CE) formation assay showed that ethyl acetate (EA) fraction of Radix rubiae significantly accentuated the CE formation, a well-recognized marker of terminal differentiation, in cultured HEK and HaCaT cells in a dose and time dependent manner. Western blot analyses demonstrated that EA fraction of Radix rubiae at a concentration of 3.2 μg/ml significantly increased transglutaminase type I and involucrin expression in both HEK and HaCaT keratinocytes after 96 h treatment, a response similar to that of Ca²⁺ positive control. Moreover, the expression level of cytokeratin 5/14, which is specifically related to cell proliferation, was significantly downregulated while terminal differentiation markers cytokeratin 1/10 were markedly increased by Radix rubiae treatment in both HEK and HaCaT cells.

Conclusion

The present experimental findings unequivocally confirmed the keratinocyte terminal differentiation promoting capacity of Radix rubiae, and strongly suggest that Radix rubiae is a promising antipsoriatic agent warranting further clinical development for psoriasis treatment.     

An ethnobotanical survey of medicinal plants used in Rwanda for voluntary depigmentation

Ethnopharmacological relevance

Voluntary depigmentation, a very common practice in sub-Saharan Africa, often performed with pharmaceutical products diverted from their pharmacological use, may cause severe dermatological and systemic side effects. The present work aims at investigating whether and which herbs were used in Rwanda for similar purposes before the advent of the current depigmentation craze; this may give clues at herbal treatments possibly advantageous compared to current products.

Material and methods

Sixty-one traditional healers, mostly representatives of their associations, were surveyed by questionnaires for knowledge and practice of voluntary depigmentation. Recipes or plants used, plant parts, harvest area, preparation methods, dosage and route of administration were recorded. Most of the cited herbs were harvested with the help of traditional healers and identified by comparison with voucher specimens; herbal vouchers of the five most cited herbs were deposited in official herbaria.

Results

All surveyed traditional healers have knowledge of voluntary depigmentation; the population currently practicing do not recourse to their services but obtain bleaching products directly from the market. Traditional healers disclosed recipes prescribed or self-used (often by women) in their youth; others cited recipes are used to treat skin diseases with properties of “clarification”, “black skin stain removal”, in cases of hyperpigmentation, and/or “skin softening”. Curiously, from the 28 recipes cited by traditional healers, all are mono-herbal preparations; most of the plants are mixed with butter for application to the skin.

Conclusion

Compared to other pathophysiological conditions, there is currently a very limited use of herbal preparations for depigmentation. Five herbs had a citation percentage equal or above to 50%, Brillantaisia cicatricosa Lindau (Acanthaceae), Chenopodium ugandae (Aellen) Aellen (Chenopodiaceae), Dolichopentas longiflora Oliv. (Rubiaceae), Protea madiensis Oliv. (Proteaceae) and Sesamum angolense Welw. (Pedaliaceae); in vitro experiments indicated a modulation of melanogenesis by these plant extracts, confirming the information obtained from traditional healers.     

Antifungal activity of the benzo[c]phenanthridine alkaloids from Chelidonium majus Linn against resistant clinical yeast isolates

Ethnopharmacological relevance

The herb of Chelidonium majus Linn is known to possess a variety of biological activities and applied in the therapy of various infectious diseases.

Aim of the study

To evaluate the in vitro antifungal activity of the active components from Chelidonium majus against clinical drug-resistant yeast isolates.

Materials and methods

Active compounds were obtained using bioassay-guided method. Six species of yeast fungi were exposed to the compounds. Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were determined according to the standard broth microdilution method.

Results

Of the six compounds determined, 8-hydroxydihydrosanguinarine (1) and 8-hydroxydihydrochelerythrine (2) demonstrated potent activity with the MIC ranges of 2–80 and 4–100 μg/mL, respectively. Dihydrosanguinarine (3), dihydrochelerythrine (4), sanguinarine (5) and chelerythrine (6) had some degree of antifungal activity.

Conclusions

The overall results provided important information for the potential application of the 8-hydroxylated alkaloids from Chelidonium majus in the therapy of serious infection caused by drug-resistant fungi.     

Transport properties of puerarin and effect of Radix Angelicae Dahuricae extract on the transport of puerarin in Caco-2 cell model

Ethnopharmacological relevance

Angelicae Dahurica (Hoffm.)Benth.& Hook.f.ex Franch.&Sav combined with Pueraria labota (Willd.)Ohwi has been widely used as herb-pairs in traditional Chinese medicine (TCM) for utilization of antipyretic analgesic and anti-inflammatory drugs, and modern pharmacological studies have shown that application compatibility of the two drugs has the effects of cardiovascular disease treatment. The previous study has proved that Radix Angelicae Dahuricae extract could enhance the intestinal absorption of puerarin in Pueraria. But the underlying compatibility mechanism of the two herbs remains unknown. In this study we tried to further evaluate the improvement of Radix Angelicae Dahuricae extract on the puerarin using the Caco-2 cell model and explore the transport properties of puerarin through the above research to discuss the possible effect mechanism of Radix Angelicae Dahuricae extract on the transport of puerarin and the underlying compatibility mechanism of the two herbs.

Aim of study

The aim of this work was to study the transport properties of puerarin in Radix Pueraria across Caco-2 cell membrane and to explore how the Radix Angelicae Dahuricae extract affected the transport of puerarin using the well-characterized, human-based intestinal Caco-2 cell model as a platform.

Materials and methods

The bidirectional transport, and the effects of time, drug concentration, pH, P-gp inhibitors (Verapamil, Cyclosporin A), MRP inhibitor (MK-571) and EDTA-Na₂ (tight junction modulator) on the absorption of puerarin were observed. Then the influence of extract of Radix Angelicae Dahuricae on the transport of puerarin was studied. Drug concentration was measured by HPLC and the apparent permeability coefficients (Papp) and apparent permeability ratio (PDR) were calculated.

Results and conclusions

The results showed that the transport (Papp) of puerarin in Caco-2 cell monolayer model had time and concentration dependence, and the transport showed saturation characteristics with the time and concentration of puerarin to a certain degree. The Papp of puerarin transported on Caco-2 cell monolayer model was significantly changed when the specified inhibitors of P-gp were added to the model and the PDR decreased from 1.74 to 0.43. The absorption of puerarin was improved when combined with Radix Angelicae Dahuricae. The intestinal absorption of puerarin is by passive diffusion as the dominating process and active transportation was mediated by P-gp and MRP transporter in Caco-2 cell monolayer model, and Radix Angelicae Dahuricae could enhance the intestinal absorption of puerarin.     

Elucidation of the transport mechanism of baicalin and the influence of a Radix Angelicae Dahuricae extract on the absorption of baicalin in a Caco-2 cell monolayer model

Ethnopharmacological relevance

Angelicae Dahurica (Hoffm.) Benth. & Hook. f. ex Franch. & Sav combined with Radix Scutellariae baicalensis Georgi has been widely used in traditional Chinese medicine (TCM) as an antipyretic analgesic and anti-inflammatory drug. Modern pharmacological studies have demonstrated that the compatible application of these two drugs is an effective treatment for hepatitis. A previous study indicated that a Radix Angelicae Dahuricae extract enhanced the intestinal absorption of the baicalin found in Radix Scutellariae; however, the underlying compatibility mechanism of these two herbs remains unknown. In this study, we further examined the effect of a Radix Angelicae Dahuricae extract on the absorption and transport properties of baicalin in a Caco-2 cell model to determine the compatibility mechanism of these two herbs.

Aim of the study

The aim of this work was to study the transport properties of baicalin in Radix Scutellariae across cell membranes and the effects of a Radix Angelicae Dahuricae extract on baicalin absorption using the well-characterized, human-based intestinal Caco-2 cell model.

Materials and methods

We assessed the absorption, bidirectional transport and toxicity of baicalin using a range of parameters, including drug concentration, pH, a P-glycoprotein (P-gp) inhibitor (Verapamil), an MRP inhibitor (MK-571) and EDTA-Na₂ (tight junction modulator). Next, we studied the influence of a Radix Angelicae Dahuricae extract on the transport of baicalin under the same conditions. Drug concentration was measured by HPLC, and the apparent permeability coefficient (Papp) and apparent permeability ratio (PDR) were subsequently calculated.

Results

The results showed that baicalin is non-toxic within a concentration range of 800 µg/mL to 4800 µg/mL. The transport of baicalin showed time and concentration dependence. The absorption of baicalin was optimal at pH 7.4 in 37 °C; however, the absorption decreased at 4 °C. The Papp of baicalin transport through the Caco-2 cell monolayer model was altered when specific inhibitors of P-gp or MRP were added to the cells. However, there was no significant difference in the PDR value. The Papp of baicalin improved when it was combined with the Radix Angelicae Dahuricae extract. The influence of EDTA-Na₂ on the transport of baicalin showed that the permeability of baicalin significantly increased. The result further indicated that the mechanism of baicalin intestinal absorption in the Caco-2 cell monolayer involves passive transcellular diffusion.

Conclusions

Passive diffusion is the main mode of intestinal absorption of bacalin and it involved in the efflux of proteins. The enhanced intestinal absorption of baicalin by Radix Angelicae Dahuricae can be due to opening of the tight junctions between cells and inhibition of MRP efflux protein expression or function.