Polymethoxylated flavonoids in citrus fruits: absorption, metabolism, and anticancer mechanisms against breast cancer.

Polymethoxylated flavonoids (PMFs) are a subclass of flavonoids found in citrus fruits that have shown multifunctional biological activities and potential anticancer effects against breast cancer. We studied the absorption, metabolism, species source, toxicity, anti-cancer mechanisms, and molecular targets of PMFs to better utilize their anticancer activity against breast cancer. We discuss the absorption and metabolism of PMFs in the body, including the methylation, demethylation, and hydroxylation processes. The anticancer mechanisms of PMFs against breast cancer were also reviewed, including the estrogen activity, cytochrome P-450 enzyme system, and arylhydrocarbon receptor (AhR) inhibition, along with various molecular targets and potential anticancer effects. Although PMFs may be advantageous in the prevention and treatment for breast cancer, there is a lack of clinical evidence and data to support their efficacy. Despite their promise, there is still a long way to go before PMFs can be applied clinically.

Dietary sinensetin and polymethoxyflavonoids: Bioavailability and potential metabolic syndrome-related bioactivity.

Sinensetin is among the most ubiquitous polyphenols in citrus fruit and recently has been extensively studied for its ability to prevent or treat diseases. The current literature on the bioavailability of sinensetin and its derivatives was reviewed and the potential ameliorative effects of metabolic syndrome in humans were evaluated. Sinensetin and its derivatives mainly aggregated in the large intestine and extensively metabolized through gut microbiota (GM) and the liver. So intestinal microorganisms had a significant influence on the absorption and metabolism of sinensetin. Interestingly, not only GM acted on sinensetin to metabolize them, but sinensetin also regulated the composition of GM. Thus, sinensetin was metabolized as methyl, glucuronide and sulfate metabolites in the blood and urine. Furthermore, sinensetin was reported to have the beneficial effect of ameliorating metabolic syndromes, including disorders of lipid metabolism (obesity, NAFLD, atherosclerosis), glucose metabolism disorder (insulin resistant) and inflammation, in terms of improving the composition of intestinal flora and modulating metabolic pathway factors in relevant tissues. The present work strongly elucidated the potential mechanism of sinensetin in improving metabolic disorders and supported the contribution of sinensetin to health benefits, thus offering a better perspective in understanding the role played by sinensetin in human health.

Rhamnogalacturonan I-Enriched Pectin, Flavonoids, and Alkaloids from Lotus Leaf Infusion in Regulating Glycolipid Absorption and Metabolism: Isolation, In Vitro Bioactivity Verification, and Structural Characterization.

Lotus leaf is effective in regulating glycolipid absorption and metabolism, but the roles of small-molecule compounds and polysaccharides are unknown. In this study, the small-molecule compounds including flavonoids, alkaloids, and polysaccharides were gradually isolated from lotus leaf infusion by multi-column chromatography and applied to in vitro activity verification and structural characterization. Although flavonoids and alkaloids were effective in inhibiting pancrelipase and α-glucosidase, polysaccharides more effectively bounded bile acids, inhibited cholesterol micelle solubility, and stimulated the growth of Bifidobacterium than lotus leaf infusion. Polysaccharides, presented as spherical conformation in water, were identified as rhamnogalacturonan I-enriched (93%) low-ester pectin with multiple branches mainly composed of arabinan, arabinogalactan-type II, and galactan formed by →3)-Galp-(1→, →5)-Araf-(1→ and →4)-Galp-(1→ residues. Polysaccharides, which were a key constituent of lotus leaf infusion in regulating glycolipid absorption and metabolism, should be paid more attention and developed as a functional food ingredient.

A comprehensive review of the metabolism of citrus flavonoids and their binding to bitter taste receptors.

Citrus is an important source of flavonoids in our daily diet. Citrus flavonoids have antioxidant, anticancer, anti-inflammatory, and cardiovascular disease prevention functions. Studies have shown that some pharmaceutical values of flavonoids may be related to their binding to bitter taste receptors, thus activating downstream signal transduction pathways; however, the underlying mechanism has not been systematically elucidated. In this paper, the biosynthesis pathway and the absorption and metabolism of citrus flavonoids were briefly reviewed, and the relationship between flavonoid structure and bitter taste intensity was investigated. In addition, the pharmacological effects of bitter flavonoids and the activation of bitter taste receptors in combating various diseases were discussed. This review provides an important basis for the targeted design of citrus flavonoid structures to make them more biologically active and more attractive as powerful drugs for the effective treatment of chronic diseases such as obesity, asthma, and neurological diseases.

Establishment and Characterization of Novel Human Intestinal In Vitro Models for Absorption and First-Pass Metabolism Studies.

Commonly used intestinal in vitro models are limited in their potential to predict oral drug absorption. They either lack the capability to form a tight cellular monolayer mimicking the intestinal epithelial barrier or the expression of cytochrome P450 3A4 (CYP3A4). The aim of this study was to establish a platform of colorectal cancer patient-derived cell lines for evaluation of human intestinal drug absorption and metabolism. We characterized ten 2D cell lines out of our collection with confluent outgrowth and long-lasting barrier forming potential as well as suitability for high throughput applications with special emphasis on expression and inducibility of CYP3A4. By assessment of the transepithelial electrical resistance (TEER) the cells barrier function capacity can be quantified. Very high TEER levels were detected for HROC60. A high basal CYP3A4 expression and function was found for HROC32. Eight cell lines showed higher CYP3A4 induction by stimulation via the vitamin D receptor compared to Caco-2 cells (5.1- to 16.8-fold change). Stimulation of the pregnane X receptor led to higher CYP3A4 induction in two cell lines. In sum, we identified the two cell lines HROC183 T0 M2 and HROC217 T1 M2 as useful tools for in vitro drug absorption studies. Due to their high TEER values and inducibility by drug receptor ligands, they may be superior to Caco-2 cells to analyze oral drug absorption and intestinal drug-drug interactions. Significance statement: Selecting appropriate candidates is important in preclinical drug development. Therefore, cell models to predict absorption from the human intestine are of the utmost importance. This study revealed that the human cell lines HROC183 T0 M2 and HROC217 T1 M2 may be better suited models and possess higher predictive power of pregnane X receptor- and vitamin D-mediated drug metabolism than Caco-2 cells. Consequently, they represent useful tools for predicting intestinal absorption and simultaneously enable assessment of membrane permeability and first-pass metabolism.

Updated design strategies for oral delivery systems: maximized bioefficacy of dietary bioactive compounds achieved by inducing proper digestive fate and sensory attributes.

Interest in the application of dietary bioactive compounds (DBC) in healthcare and pharmaceutical industries has motivated researchers to develop functional delivery systems (FDS) aiming to maximize their bioefficacy. As the direct and indirect health benefiting effects of DBC are acknowledged, traditional design principle of FDS aiming at improving the bioavailability of intact DBC is challenged by the updated one, where the maximized bioefficacy of DBC delivered by FDS will be achieved via rationally absorbed at target sites with proper metabolism pathways. This article briefly summarized the absorption and metabolic fates of orally digested DBC along with their direct and indirect mechanisms to perform health benefiting effects. Current strategies in designing the next generation FDS with an emphasis on their modulation effects on the distribution portion between the upper and lower digestive tract, portal vein and lymphatic absorption, human digestive and gut microbiota enzymatic mediated metabolism were highlighted. Updated research progresses of FDS in adjusting sensory attributes of food end products and inducing synergistic effects rooting from matrix materials and co-delivered cargos were also discussed. Challenges as well as future perspectives concerning the precise nutrition and the critical role of delivery systems in dietary intervention were proposed.

Study on pharmacological properties and cell absorption metabolism of novel daidzein napsylates.

Novel daidzein napsylates (DD4 and DD5) were synthesized by microwave irradiation, according to structural modification of daidzein (DAI) using the principle of pharmacokinetic transformation. The pharmacological properties of DD4 and DD5 were evaluated via high performance liquid chromatography (HPLC) and calculated based on the drug design software ChemAxon 16.1.18. The cell uptake changes of DD4 and DD5 were investigated to analyse the structure-property relationship. The metabolisms of DD4 and DD5 were analysed by HPLC-mass spectrometry in human aortic vascular smooth muscle cells (HAVSMCs) and their possible metabolic pathways were inferred in vivo. The results showed that the solubility of DD4 and DD5 was increased by 2.79 × 105 and 2.16 × 105 times compared to that of DAI, separately, in ethyl acetate. The maximum absorption rates of DD4 and DD5 were enhanced by 4.3-4.5 times relative to DAI. Preliminary studies on metabolites of DD4 and DD5 in HAVSMCs showed that DD4 and DD5 were hydrolysed into DAI under the action of intracellular hydrolase in two ways, ester hydrolysis or ether hydrolysis. Then, DAI was combined with glucuronic acid to form daidzein monoglucuronate under the action of uridine diphosphate (UDP)-glucuronidase. Meanwhile, it was also found that metabolite M5 of DD5 could undergo glucuronidation under the action of UDP-glucuronosyltransferase and competitive sulphation under the action of sulphotransferase to produce its sulfate conjugate M7. Analysis of structure-property relationships indicated that the absorption and utilization of drugs is closely relative to the physical properties and could be improved by adjusting the liposolubility. The pharmaceutical properties were optimized comprehensively after DAI was modified by naphthalene sulphonate esterification. This indicates that this kind of derivatives may have relatively good absorption and transport characteristics and biological activities in vivo. The research on biological activities of the new derivatives (DD4 and DD5) is ongoing in our laboratory.

Anti-Inflammatory Action and Mechanisms of Resveratrol.

Resveratrol (3,4',5-trihy- droxystilbene), a natural phytoalexin polyphenol, exhibits anti-oxidant, anti-inflammatory, and anti-carcinogenic properties. This phytoalexin is well-absorbed and rapidly and extensively metabolized in the body. Inflammation is an adaptive response, which could be triggered by various danger signals, such as invasion by microorganisms or tissue injury. In this review, the anti-inflammatory activity and the mechanism of resveratrol modulates the inflammatory response are examined. Multiple experimental studies that illustrate regulatory mechanisms and the immunomodulatory function of resveratrol both in vivo and in vitro. The data acquired from those studies are discussed.

The dynamic process of dietary soybean ß-conglycinin in digestion, absorption, and metabolism among different intestinal segments in grass carp (Ctenopharyngodon idella).

The present study aimed to investigate the dynamic process of soybean ß-conglycinin in digestion, absorption, and metabolism in the intestine of grass carp (Ctenopharyngodon idella). Fish fed with 80 g ß-conglycinin/kg diet for 7 weeks, the intestinal digestive enzyme was extracted to hydrolyze ß-conglycinin in vitro, the free amino acid and its metabolism product contents in intestinal segments were analyzed. The present study first found that ß-conglycinin cannot be thoroughly digested by fish intestine digestive enzyme and produces new products (about 60- and 55-kDa polypeptides). The indigestible ß-conglycinin further caused the free amino acid imbalance, especially caused free essential amino acid deficiency in the proximal intestine but excess in the distal intestine. Moreover, these results might be partly associated with the effect of ß-conglycinin in amino acid transporters and tight junction-regulated paracellular pathway. Finally, dietary ß-conglycinin increased the content of amino acid catabolism by-product ammonia while decreased the amino acid anabolism product carnosine content in the proximal intestine and distal intestine. Thus, the current study first and systemically explored the dynamic process of ß-conglycinin in digestion, absorption, and metabolism, which further supported our previous study that dietary ß-conglycinin suppressed fish growth and caused intestine injure.

Absorption and Metabolism of γ-Oryzanol, a Characteristic Functional Ingredient in Rice Bran.

γ-Oryzanol (OZ), a functional substance found in rice bran, consists of multiple molecular species. In both in vitro and in vivo studies, the researches exploring the various function of rice bran OZ have been conducted for a long time, and it has become clear that OZ has a lot of pharmaceutical activities. It is assumed that each type of OZ molecular species may have different effects. In contrast, the profile behaviour of OZ inside the body has not been fully understood. This article reviews the previous studies about the digestion, absorption, metabolism, and effects of rice bran OZ and also introduces the new method to evaluate the OZ metabolic fate by using high-performance liquid chromatography (HPLC) combined with tandem mass-spectrometry (MS/MS) which has higher selectivity and sensitivity.

Comparison of Blood Profiles of γ-Oryzanol and Ferulic Acid in Rats after Oral Intake of γ-Oryzanol.

γ-Oryzanol (OZ), a bioactive phytochemical abundant in cereals such as rice, has been reported to be mainly hydrolyzed to ferulic acid (FA) in the body. Meanwhile, in our previous study, we revealed that a part of OZ is absorbed into the body and exists in its intact form. However, the comprehensive absorption profile of OZ and its metabolites (e.g., FA) after OZ intake has not been fully elucidated yet. Therefore, in this study, we measured the concentrations of OZ, FA, and FA conjugates (i.e., FA sulfate and glucuronide) in the blood of rats with the use of HPLC-MS/MS after a single oral administration of 300 µmol/kg body weight of rice bran OZ (RBOZ). As a result, intact OZ along with FA and FA conjugates existed in the blood, which implied that these constituents may all contribute to the physiological effects under OZ intake. Additionally, when an equimolar amount of FA (300 µmol/kg body weight) was administered, it was found that the absorption profile of FA was significantly different from that when RBOZ was administered.

Evaluation of γ-oryzanol Accumulation and Lipid Metabolism in the Body of Mice Following Long-Term Administration of γ-oryzanol.

γ-Oryzanol (OZ), abundant in rice bran oil, has gained attention due to its physiological activities (e.g., lipid-lowering effects). However, the absorption and metabolism of orally ingested OZ have not yet been fully elucidated. In this study, diets containing normal or high contents of OZ were fed to obesity model mice for 8 weeks, and OZ concentrations in plasma and organs were analyzed by HPLC-MS/MS. To evaluate the relationship between OZ accumulation and lipid metabolism in vivo, lipid concentrations in the mice plasma and liver were also measured. As a result, the accumulation of intact OZ in plasma and organs was seen in mice fed diets containing OZ, where mice fed diets containing higher OZ contents demonstrated higher levels of OZ accumulation and lower amounts of plasma lipids. These results, in combination with our additional data from a single oral administration test, suggest the possibility that intact OZ, along with its metabolites (e.g., ferulic acid), is biologically-active.

Intestinal absorption differences of major bioactive compounds of Gegenqinlian Decoction between normal and bacterial diarrheal mini-pigs in vitro and in situ.

Intestinal condition plays an important role in drug absorption and metabolism, thus the effects of varied gastrointestinal diseases such as infectious diarrhea on the intestinal function are crucial for drug absorption. However, due to the lack of suitable models, the differences of absorption and metabolism of drugs between the diarrheal and normal intestines are rarely reported. Thus, in this study, Escherichia coli diarrhea model was induced in mini-pigs and single-pass intestinal perfusion and intestinal mucosal enzyme metabolism experiments were conducted. A simple and rapid ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to determine the concentrations of 9 major components in Gegen Qinlian decoction (GQD). Samples were pretreated by protein precipitation with methanol and naringin and prednisolone were used as internal standards. The validated method demonstrated adequate sensitivity, selectivity, and process efficiency for the bioanalysis of 9 compounds. Results of intestinal perfusion showed that puerarin, daidzein, daidzin and baicalin and berberine were absorbed faster in diarrheal jejunum than in normal intestines (p < 0.05). However, puerarin, daidzin and liquiritin were metabolized more slowly in diarrheal intestine after incubation compared with the normal group (p < 0.05). The concentrations of daidzein in both perfusion and metabolism and wogonin in metabolism were significantly increased (p < 0.05). In conclusion, absorption and metabolism of GQD were significantly different between the diarrheal and normal intestines, which suggest that bacterial diarrheal mini-pigs model can be used in the intestinal absorption study and is worthy to be applied in the other intestinal absorption study of anti- diarrheal drugs.

Bioavailability and metabolism of rosemary infusion polyphenols using Caco-2 and HepG2 cell model systems.

BACKGROUND: Rosmarinus officinalis is an aromatic plant used in folk medicine as a result of the therapeutic properties associated with its phenolic composition, being rich in rosmarinic acid (RA) and caffeic acid (CA). To better understand the bioactivity of these compounds, their absorption and metabolism were assessed in human Caco-2 and HepG2 cells, as small intestine and liver models, respectively, using RA and CA standards, as well as a rosemary infusion and ferulic acid (FA). RESULTS: Test compounds were partially up-taken and metabolized by Caco-2 and HepG2 cells, although a higher metabolization rate was observed after hepatic incubation compared to intestinal incubation. CA was the compound best absorbed followed by RA and FA, showing metabolites percentages of 30.4%, 11.8% and 4.4% in Caco-2 and 34.3%, 10.3% and 3.2% in HepG2 cells, respectively. RA in the rosemary infusion showed improved bioavailability compared to pure RA. Methyl derivatives were the main metabolites detected for CA and RA after intestinal and hepatic metabolism, followed by methyl-glucuronidates and glucuronidates. RA was also minimally hydrolyzed into CA, whereas FA only was glucuronidated. Rosemary polyphenols followed the same biotransformation pathways as the standards. In addition, phase II derivatives of luteolin were observed. CONCLUSION: Rosemary polyphenols are partially metabolized in both the intestine and liver. © 2018 Society of Chemical Industry.

[Intestinal absorption and metabolism of Puerariae Lobatae Radix decoction by in situ closed-loop method].

Biopharmaceutics classification system of Chinese materia medica (CMMBCS) emphasizes characteristic of the multi-component environment based on the drug solubility and permeability. In this study, the in situ closed-loop method combined with LC-MS technique was utilized to study the intestinal absorption and metabolism of Puerariae Lobatae Radix decoction (PLRD), providing selection basis for intestinal permeability components in CMMBCS. A total of 36 components were identified from PLRD. Among them, 17 components could be detected in the plasma sample, indicating that 17 components could be absorbed into blood, so these 17 components could be used as intestinal permeability evaluation components in CMMBCS. The other 19 components were not detected in the plasma sample, suggesting that they may not be absorbed or metabolized by the gut wall enzymes.

Effect of supplemental concentrate during the dry period or early lactation on rumen epithelium gene and protein expression in dairy cattle during the transition period.

We previously reported 2 experiments with rumen-cannulated Holstein-Friesian dairy cows showing that during the transition period, rumen papillae surface area, and fractional absorption rate of volatile fatty acids (VFA) increase after calving. However, supplemental concentrate during the dry period and rate of increase of concentrate allowance during lactation affected papillae surface area, but not VFA absorption. Here we report the changes in gene and protein expression in rumen papillae related to tissue growth and VFA utilization. The lactation experiment treatment consisted of a rapid [RAP; 1.0 kg of dry matter (DM)/d; n = 6] or gradual (GRAD; 0.25 kg of DM/d; n = 6) increase of concentrate allowance (up to 10.9 kg of DM/d), starting at 4 d postpartum (pp). The dry period experiment treatment consisted of 3.0 kg of DM/d of concentrate (n = 4) or no concentrate (n = 5) during the last 28 d of the dry period. Real-time quantitative PCR analysis of rumen papillae showed that the expression of apoptosis-related genes was neither affected by day nor its interaction with treatment for both experiments. Expression of epithelial transporter genes was not affected by day or treatment in the lactation experiment, except for NBC1. In the dry period experiment, expression of MCT1, NBC1, DRA, NHE2, NHE3, and UT-B generally decreased after calving. A day and treatment interaction was observed for ATP1A1 in the dry period experiment, with greater expression at 18 and 8 d antepartum for concentrate than no concentrate. Generally, expression of VFA metabolism-related genes was not affected by day or its interaction with treatment. In the lactation experiment, immunoblotting of 5 selected genes showed that protein expression of DRA and PCCA was greater at 16 d pp compared with 3 and 44 d pp. Expression of NHE2 was greater, and that of ATP1A1 lower, at 16 and 44 d pp compared with 3 d pp, suggesting alterations in intracellular pH regulation and sodium homeostasis. Both MCT1 and PCCA protein were upregulated by RAP from 3 to 16 d pp, indicating modulations in VFA metabolism. Our data suggests that VFA absorption and metabolic capacity changed little per unit of surface area during the transition period, and suggests that a change in mitosis rate rather than apoptosis rate is associated with the increased ruminal VFA production, resulting in tissue growth. A significant but weak correlation between the examined gene and protein expression levels was observed only for PCCA, indicating that care must be taken when interpreting results obtained at either level.

Intestinal absorption and metabolism of Puerariae Lobatae Radix decoction by in situ closed-loop method / 中国中药杂志

Biopharmaceutics classification system of Chinese materia medica (CMMBCS) emphasizes characteristic of the multi-component environment based on the drug solubility and permeability. In this study, the in situ closed-loop method combined with LC-MS technique was utilized to study the intestinal absorption and metabolism of Puerariae Lobatae Radix decoction (PLRD), providing selection basis for intestinal permeability components in CMMBCS. A total of 36 components were identified from PLRD. Among them, 17 components could be detected in the plasma sample, indicating that 17 components could be absorbed into blood, so these 17 components could be used as intestinal permeability evaluation components in CMMBCS. The other 19 components were not detected in the plasma sample, suggesting that they may not be absorbed or metabolized by the gut wall enzymes.

Characteristics of dairy cows with a greater or lower risk of subacute ruminal acidosis: Volatile fatty acid absorption, rumen digestion, and expression of genes in rumen epithelial cells.

The objective of this study was to examine whether lactating dairy cows with a greater or lower risk of subacute ruminal acidosis (SARA) have differences in volatile fatty acid (VFA) absorption rate, expression of genes involved in VFA metabolism and intracellular pH regulation in rumen epithelial cells, and in situ carbohydrate digestibility in the rumen. We fed 14 ruminally cannulated mid-lactating dairy cows (119±47.2d in milk; body weight 640±47.9kg) a high-grain diet consisting of 30% forage ad libitum, with an 18-d diet adaptation and a 7-d sample and data collection period. Eight cows with the lowest acidosis index [area below pH 5.8 normalized for dry matter intake (DMI); 0.10±0.16 pH × min/kg of DMI] and 5 with the highest acidosis index (3.72±0.19 pH × min/kg of DMI) were classified as animals with lower risk (LS) and higher risk (HS) of SARA, respectively. Minimum (5.75 vs. 5.33) and mean rumen pH (6.33 vs. 5.98) were higher for LS than for HS cows. In addition, the duration and area of rumen pH below 5.8 was lower in LS cows (24.9 vs. 481min/d; 2.94 vs. 102 pH × min/d). Although DMI, milk yield, and milk component yields did not differ, milk fat concentration tended to be higher for LS cows than for HS cows (3.36 vs. 2.93%). However, we observed no difference in VFA absorption rate between LS and HS cows. In situ starch and neutral detergent fiber digestibility were not different between LS and HS cows, but the relative mRNA abundance of lanosterol synthase (LSS) was higher for LS cows than for HS cows. In addition, the mRNA abundance of hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) tended to be higher for LS cows than for HS cows. These results suggested that VFA absorption rate might not explain the difference in rumen pH between LS and HS cows in the current study, even though expression of some genes related to VFA metabolism in rumen epithelium may be associated with variation in the risk of SARA among lactating cows. This variation in the risk of SARA may not be attributed to differences in the capacity of rumen microbes to ferment carbohydrates, because in situ carbohydrate digestibility in the rumen was not different between cows with higher and lower risk of SARA.

Metabolic routes along digestive system of licorice: multicomponent sequential metabolism method in rat.

This study was conducted to establish the multicomponent sequential metabolism (MSM) method based on comparative analysis along the digestive system following oral administration of licorice (Glycyrrhiza uralensis Fisch., leguminosae), a traditional Chinese medicine widely used for harmonizing other ingredients in a formulae. The licorice water extract (LWE) dissolved in Krebs-Ringer buffer solution (1 g/mL) was used to carry out the experiments and the comparative analysis was performed using HPLC and LC-MS/MS methods. In vitro incubation, in situ closed-loop and in vivo blood sampling were used to measure the LWE metabolic profile along the digestive system. The incubation experiment showed that the LWE was basically stable in digestive juice. A comparative analysis presented the metabolic profile of each prototype and its corresponding metabolites then. Liver was the major metabolic organ for LWE, and the metabolism by the intestinal flora and gut wall was also an important part of the process. The MSM method was practical and could be a potential method to describe the metabolic routes of multiple components before absorption into the systemic blood stream. Copyright © 2015 John Wiley & Sons, Ltd.

[Absorption and metabolism of icariin in different osteoporosis rat models].

To compare the intestinal absorption and metabolism of icariin in different osteoporosis rat models. Ovariectomy and intragastric administration of cyclophosphamide were used to establish two kinds of rat osteoporosis models. Then the rat intestinal perfusion was conducted, and HPLC was used to measure and calculate the permeability coefficients of icariin in different intestines and production amount of metabolites. Western blot was used to detect LPH enzyme expression in two models. Experimental results showed that both ovariectomy and intragastric administration of cyclophosphamide 4.5 mg•kg⁻¹ could reduce rat bone density and successfully construct the rat osteoporosis models. The apparent permeability coefficient Papp of 20 µmol icariin in duodenum, jejunum, ileum, colon was 5.695, 5.224, 1.492, 0.520 respectively in sham operation group; 3.876, 3.608, 0.863, and 0.291 in ovariectomized group; 4.945, 3.601, 1.990, 1.042 in normal saline group; 3.301, 2.108, 1.209, 1.233 in cyclophosphamide-induced osteoporosis model group. In addition, the protein expression levels of LPH enzyme in two model groups were lower than those in normal group. The absorption and metabolism of icariin in two kinds of osteoporosis models was lower than that in sham operation group and normal saline group; the reduction of expression level of LPH enzymes in rat intestine of different osteoporosis models was one of the reasons for leading to the reduced intestinal absorption and metabolism of icariin.