Bithiophene-Functionalized Infrared Two-Photon Absorption Metal Complexes as Single-Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy.

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100 % survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.

Iridium(III)-Based Infrared Two-Photon Photosensitizers: Systematic Regulation of Their Photodynamic Therapy Efficacy.

Cyclometalated iridium(III) complexes are of significant importance in the field of antitumor photodynamic therapy (PDT), whether they exist as single molecules or are incorporated into nanomaterials. Nevertheless, a comprehensive examination of the relationship between their molecular structure and PDT effectiveness remains awaited. The influencing factors of two-photon excited PDT can be anticipated to be further multiplied, particularly in relation to intricate nonlinear optical properties. At present, a comprehensive body of research on this topic is lacking, and few discernible patterns have been identified. In this study, through systematic structure regulation, the nitro-substituted styryl group and 1-phenylisoquinoline ligand containing YQ2 was found to be the most potent infrared two-photon excitable photosensitizer in a 4 × 3 combination library of cyclometalated Ir(III) complexes. YQ2 could enter cells via an energy-dependent and caveolae-mediated pathway, bind specifically to mitochondria, produce 1O2 in response to 808 nm LPL irradiation, activate caspases, and induce apoptosis. In vitro, YQ2 displayed a remarkable phototherapy index for both malignant melanoma (>885) and non-small-cell lung cancer (>1234) based on these functions and was minimally deleterious to human normal liver and kidney cells. In in vivo antitumor phototherapy, YQ2 inhibited tumor growth by an impressive 85% and could be eliminated from the bodies of mice with a half-life as short as 43 h. This study has the potential to contribute significantly to the development of phototherapeutic drugs that are extremely effective in treating large, profoundly located solid tumors as well as the understanding of the structure-activity relationship of Ir(III)-based PSs in PDT.

Berberine interacts with gut microbiota and its potential therapy for polycystic ovary syndrome.

Berberine (BBR) is an isoquinoline alkaloid extracted from Chinese medicinal plants showing a tight correlation with gut microbiota. Polycystic ovary syndrome (PCOS) is a prevalent reproductive and endocrine disorder syndrome among women of childbearing age. Dysbiosis, the imbalance of intestinal microorganisms, is a potential factor that takes part in the pathogenesis of PCOS. Recent evidence indicates that berberine offers promise for treating PCOS. Here, we review the recent research on the interaction between berberine and intestinal microorganisms, including the changes in the structure of gut bacteria, the intestinal metabolites after BBR treatment, and the effect of gut microbiota on the bioavailability of BBR. We also discuss the therapeutic effect of BBR on PCOS in terms of gut microbiota and its potential mechanisms.

Antioxidant vitamins supplementation reduce endometriosis related pelvic pain in humans: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to clarify the effect of antioxidant vitamins supplementation on endometriosis-related pain. METHODS: A systematic search of PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNK) databases was conducted to identify relevant studies published in English and Chinese up to 16 March 2023. The search terms used were "endometriosis" OR "endometrioma" OR "endometrium" AND "antioxidant" OR "Vitamin C" OR "Vitamin E" OR "Vitamin D" OR "25-OHD" OR "25(OH)D" OR "25-hydroxyvitamin D". Eligible studies were randomized controlled trials (RCTs) that assessed pain scores using the Visual Analogue Scale (VAS). Mean differences or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the effect of antioxidant vitamins supplementation on endometriosis. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS: A total of 13 RCTs involving 589 patients were included in this meta-analysis. We identified 11 studies that evaluated the effect of antioxidant vitamins supplementation on endometriosis-related pain. The results indicated that the supplementation of antioxidant vitamins can effectively alleviate endometriosis-related pain. Subgroup analysis showed that the supplementation of vitamin E (with or without vitamin C) had a positive effect on improving clinical pelvic pain in patients with chronic pelvic pain. Conversely, supplementation of vitamin D was associated with a reduction in pelvic pain in endometriosis patients, but the difference was not statistically significant compared to the placebo. Additionally, we observed changes in oxidative stress markers following vitamin supplementation. Plasma malondialdehyde (MDA) concentration decreased in patients with endometriosis after antioxidant vitamin supplementation, and the plasma MDA level was inversely correlated with the time and dose of vitamin E and C supplementation. Furthermore, the inflammatory markers in peritoneal fluid, including RANTES, interleukin-6, and monocyte chemoattractant protein-1, significantly decreased after antioxidant therapy. These findings suggest that antioxidant vitamins may alleviate pain in endometriosis patients by reducing inflammation. CONCLUSIONS: The included studies support the potential role of antioxidant vitamins in the management of endometriosis. Supplementation with antioxidant vitamins effectively reduced the severity of dysmenorrhea, improved dyspareunia and pelvic pain, and enhanced quality of life in these patients. Therefore, antioxidant vitamin therapy could be considered as an alternative treatment method, either alone or in combination with other approaches, for endometriosis-related pain. TRIAL REGISTRATION: PROSPERO registration number: CRD42023415198.

Bleeding the Excited State Energy to the Utmost: Single-Molecule Iridium Complexes for In Vivo Dual Photodynamic and Photothermal Therapy by an Infrared Low-Power Laser.

A series of cyclometalated Ir(III) complexes with morpholine and piperazine groups are designed as dual photosensitizers and photothermal agents for more efficient antitumor phototherapy via infrared low-power laser. Their ground and excited state properties, as well as the structural effect on their photophysical and biological properties, are investigated by spectroscopic, electrochemical, and quantum chemical theoretical calculations. They target mitochondria in human melanoma tumor cells and trigger apoptosis related to mitochondrial dysfunction upon irradiation. The Ir(III) complexes, particularly Ir6, demonstrate high phototherapy indexes to melanoma tumor cells and a manifest photothermal effect. Ir6, with minimal hepato-/nephrotoxicity in vitro, significantly inhibits the growth of melanoma tumors in vivo under 808 nm laser irradiation by dual photodynamic therapy and photothermal therapy and can be efficiently eliminated from the body. These results may contribute to the development of highly efficient phototherapeutic drugs for large, deeply buried solid tumors.

Selenium and Selenoproteins in Health.

Selenium is a trace mineral that is essential for health. After being obtained from food and taken up by the liver, selenium performs various physiological functions in the body in the form of selenoproteins, which are best known for their redox activity and anti-inflammatory properties. Selenium stimulates the activation of immune cells and is important for the activation of the immune system. Selenium is also essential for the maintenance of brain function. Selenium supplements can regulate lipid metabolism, cell apoptosis, and autophagy, and have displayed significant alleviating effects in most cardiovascular diseases. However, the effect of increased selenium intake on the risk of cancer remains unclear. Elevated serum selenium levels are associated with an increased risk of type 2 diabetes, and this relationship is complex and nonlinear. Selenium supplementation seems beneficial to some extent; however, existing studies have not fully explained the influence of selenium on various diseases. Further, more intervention trials are needed to verify the beneficial or harmful effects of selenium supplementation in various diseases.

1α,25-Dihydroxyvitamin D3 Improves Follicular Development and Steroid Hormone Biosynthesis by Regulating Vitamin D Receptor in the Layers Model.

1α,25-Dihydroxyvitamin D3 (VitD3) is the active form of vitamin D, and it regulates gene expression and protein synthesis in mammalian follicle development. However, the function of VitD3 in the follicular development of layers remains unclear. This study investigated, through in vivo and in vitro experiments, the effects of VitD3 on follicle development and steroid hormone biosynthesis in young layers. In vivo, ninety 18-week-old Hy-Line Brown laying hens were randomly divided into three groups for different treatments of VitD3 (0, 10, and 100 µg/kg). VitD3 supplementation promoted follicle development, increasing the number of small yellow follicles (SYFs) and large yellow follicles (LYFs) and the thickness of the granulosa layer (GL) of SYFs. Transcriptome analysis revealed that VitD3 supplementation altered gene expression in the ovarian steroidogenesis, cholesterol metabolism, and glycerolipid metabolism signaling pathways. Steroid hormone-targeted metabolomics profiling identified 20 steroid hormones altered by VitD3 treatment, with 5 being significantly different among the groups. In vitro, it was found that VitD3 increased cell proliferation, promoted cell-cycle progression, regulated the expression of cell-cycle-related genes, and inhibited the apoptosis of granulosa cells from pre-hierarchical follicles (phGCs) and theca cells from prehierarchical follicles (phTCs). In addition, the steroid hormone biosynthesis-related genes, estradiol (E2) and progesterone (P4) concentrations, and vitamin D receptor (VDR) expression level was significantly altered by VitD3. Our findings identified that VitD3 altered the gene expression related to steroid metabolism and the production of testosterone, estradiol, and progesterone in the pre-hierarchical follicles (PHFs), resulting in positive effects on poultry follicular development.

Tiao-bu-fei-shen formula promotes downregulation of the caveolin 1-p38 mapk signaling pathway in COPD - Associated tracheobronchomalacia cell model.

ETHNOPHARMACOLOGICAL RELEVANCE: The Tiao-bu-fei-shen (TBFS) formula, extensively used in Traditional Chinese Medicine (TCM), can enhance therapeutic efficacy and reduce the frequency of acute exacerbations of lung-kidney Qi deficiency in patients with chronic obstructive pulmonary disease (COPD). According to both TCM theory and long-term observation of practice, TBFS has become an effective treatment for COPD-associated tracheobronchomalacia (TBM). AIM OF THE STUDY: To investigate the mechanism of the TBFS formula in treating COPD-associated TBM based on caveolin 1-p38 MAPK signaling and apoptosis. MATERIALS AND METHODS: A rat COPD model was prepared by exposure to smoking combined with tracheal lipopolysaccharide injection. The trachea or bronchus chondrocytes from COPD rats were isolated, cultured, and treated with 10 ng/mL IL-1ß for 24 h to develop a model of COPD-associated TBM. Normal rats were administered TBFS to prepare drug-containing serum, and CCK8 assays were used to screen the optimal drug-containing serum concentration and SB203580 dose. TBFS drug-containing serum and SB203580 were processed separately for the control, model, drug-containing serum, blocker, and drug-containing serum combined with blocker groups. Flow cytometry and CCK8 assays were used to detect apoptosis and proliferative activity. Toluidine blue staining and immunohistochemistry were used to analyze the chondrocyte proteoglycan and type II collagen content. Western blotting was used to detect the expression of caveolin 1, p-p38 MAPK, TNF-α, IL-1ß, MMP-13, Bax, and Bcl-2 proteins. Quantitative PCR was used to detect the expression of caveolin 1, p38 MAPK, IL-1ß, MMP-13, Bax, Bcl-2, and miR-140-5p. RESULTS: The isolation and identification of bronchial chondrocytes from COPD rats revealed that 10 ng/mL IL-1ß can produce a stable COPD-associated TBM model. Screened via the CCK8 method, fourth-generation bronchial chondrocytes were determined as the optimal cells, and 5 µM SB203580 and 5% low-dose drug-containing serum were the optimal intervention doses. The experimental chondrocytes of each group were treated separately for 48 h. Toluidine blue staining and immunohistochemical analysis revealed that TBFS drug-containing serum, SB203580, and TBFS drug-containing serum combined with SB203580 can effectively increase the proteoglycan and type II collagen content after chondrocyte degradation. Flow cytometry of cells treated with SB203580 and TBFS drug-containing serum combined with SB203580 revealed significantly reduced cell apoptosis and enhanced cell proliferation activity. Western blot and qPCR analyses revealed that the TBFS drug-containing serum, SB203580, and TBFS drug-containing serum combined with SB203580 effectively inhibit the expression of caveolin 1, p-p38 MAPK, MMP-13, IL-1ß, TNF-α, and Bax proteins while promoting Bcl -2 protein expression. Treatment with TBFS drug-containing serum and SB203580 effectively inhibited the expression of MMP-13, p38 MAPK, caveolin 1, and Bax genes, and promoted the expression of Bcl-2 and miR-140-5p genes. CONCLUSIONS: A concentration of 10 ng/mL of IL-1ß can generate a stable COPD-associated TBM cell model. TBFS can improve the proteoglycan and type II collagen content, increase cell activity, and reduce the amount of chondrocyte apoptosis. The role of TBFS may be related to mechanisms of inhibiting the expression of the key signaling molecules caveolin 1 and p-p38 MAPK in the caveolin 1-p38 MAPK signaling pathway, thereby reducing the expression of the downstream effector products MMP-13, IL-1ß, and TNF-α, while inhibiting the expression of the apoptotic gene Bax and improving the expression of Bcl-2 and miR-140-5p genes.

Heterogeneous nutrient supply promotes maize growth and phosphorus acquisition: additive and compensatory effects of lateral roots and root hairs.

BACKGROUND AND AIMS: Root proliferation is a response to a heterogeneous nutrient distribution. However, the growth of root hairs in response to heterogeneous nutrients and the relationship between root hairs and lateral roots remain unclear. This study aims to understand the effects of heterogeneous nutrients on root hair growth and the trade-off between root hairs and lateral roots in phosphorus (P) acquisition. METHODS: Near-isogenic maize lines, the B73 wild type (WT) and the rth3 root hairless mutant, were grown in rhizoboxes with uniform or localized supply of 40 (low) or 140 (high) mg P kg-1 soil. RESULTS: Both WT and rth3 had nearly two-fold greater shoot biomass and P content under local than uniform treatment at low P. Significant root proliferation was observed in both WT and rth3 in the nutrient patch, with the WT accompanied by an obvious increase (from 0.7 to 1.2 mm) in root hair length. The root response ratio of rth3 was greater than that of WT at low P, but could not completely compensate for the loss of root hairs. This suggests that plants enhanced P acquisition through complementarity between lateral roots and root hairs, and thus regulated nutrient foraging and shoot growth. The disappearance of WT and rth3 root response differences at high P indicated that the P application reduced the dependence of the plants on specific root traits to obtain nutrients. CONCLUSIONS: In addition to root proliferation, the root response to a nutrient-rich patch was also accompanied by root hair elongation. The genotypes without root hairs increased their investment in lateral roots in a nutrient-rich patch to compensate for the absence of root hairs, suggesting that plants enhanced nutrient acquisition by regulating the trade-off of complementary root traits.

Arbuscular mycorrhizal colonization outcompetes root hairs in maize under low phosphorus availability.

BACKGROUND AND AIMS: An increase in root hair length and density and the development of arbuscular mycorrhiza symbiosis are two alternative strategies of most plants to increase the root-soil surface area under phosphorus (P) deficiency. Across many plant species, root hair length and mycorrhization density are inversely correlated. Root architecture, rooting density and physiology also differ between species. This study aims to understand the relationship among root hairs, arbuscular mycorrhizal fungi (AMF) colonization, plant growth, P acquisition and mycorrhizal-specific Pi transporter gene expression in maize. METHODS: Using nearly isogenic maize lines, the B73 wild type and the rth3 root hairless mutant, we quantified the effect of root hairs and AMF infection in a calcareous soil under P deficiency through a combined analysis of morphological, physiological and molecular factors. KEY RESULTS: Wild-type root hairs extended the rhizosphere for acid phosphatase activity by 0.5 mm compared with the rth3 hairless mutant, as measured by in situ zymography. Total root length of the wild type was longer than that of rth3 under P deficiency. Higher AMF colonization and mycorrhiza-induced phosphate transporter gene expression were identified in the mutant under P deficiency, but plant growth and P acquisition were similar between mutant and the wild type. The mycorrhizal dependency of maize was 33 % higher than the root hair dependency. CONCLUSIONS: The results identified larger mycorrhizal dependency than root hair dependency under P deficiency in maize. Root hairs and AMF inoculation are two alternative ways to increase Pi acquisition under P deficiency, but these two strategies compete with each other.

Cornel iridoid glycoside induces autophagy to protect against tau oligomer neurotoxicity induced by the activation of glycogen synthase kinase-3ß.

Tau oligomers are the etiologic molecules of Alzheimer's disease, and correlate strongly with neuronal loss and exhibit neurotoxicity. Recent evidence indicates that small tau oligomers are the most relevant toxic aggregate species. The aim of the present study was to investigate the mechanisms of cornel iridoid glycoside (CIG) on tau oligomers and cognitive functions. We injected wortmannin and GF-109203X (WM/GFX, 200 µM each) into the lateral ventricles to induce tau oligomer and memory impairment in rats. When orally administered with CIG at 60 and 120 mg/kg/day for 14 days, CIG decreased the escape latency in the Morris water maze test. We also found that CIG restored the expression of presynaptic p-synapsin, synaptophysin, and postsynaptic density-95 (PSD-95) decreased by WM/GFX in rat cortex. CIG reduced the accumulation of tau oligomers in the brain of WM/GFX rats and in cells transfected with wild type glycogen synthase kinase-3ß (wtGSK-3ß). In addition, CIG up-regulated the levels of ATG7, ATG12, Beclin-1, and LC3II in vivo and in vitro, suggesting the restoration of autophagy function. These results suggest that CIG could ameliorate memory deficits and regulate memory-associated synaptic proteins through the clearance of tau oligomers accumulation. Moreover, CIG clears tau oligomers by restoring autophagy function.

Estimating the importance of maize root hairs in low phosphorus conditions and under drought.

BACKGROUND AND AIMS: Root hairs are single-cell extensions of the epidermis that face into the soil and increase the root-soil contact surface. Root hairs enlarge the rhizosphere radially and are very important for taking up water and sparingly soluble nutrients, such as the poorly soil-mobile phosphate. In order to quantify the importance of root hairs for maize, a mutant and the corresponding wild type were compared. METHODS: The rth2 maize mutant with very short root hairs was assayed for growth and phosphorus (P) acquisition in a slightly alkaline soil with low P and limited water supply in the absence of mycorrhization and with ample P supply. KEY RESULTS: Root and shoot growth was additively impaired under P deficiency and drought. Internal P concentrations declined with reduced water and P supply, whereas micronutrients (iron, zinc) were little affected. The very short root hairs in rth2 did not affect internal P concentrations, but the P content of juvenile plants was halved under combined stress. The rth2 plants had more fine roots and increased specific root length, but P mobilization traits (root organic carbon and phosphatase exudation) differed little. CONCLUSIONS: The results confirm the importance of root hairs for maize P uptake and content, but not for internal P concentrations. Furthermore, the performance of root hair mutants may be biased by secondary effects, such as altered root growth.

The Effect of Berberine on Polycystic Ovary Syndrome Patients with Insulin Resistance (PCOS-IR): A Meta-Analysis and Systematic Review.

PURPOSE: To evaluate the effect of berberine (BBR) on polycystic ovary syndrome (PCOS) patients with insulin resistance (IR). METHODS: PubMed (in English), Medline (in English), Embase (in English), CNKI (in Chinese), WanFang DATA (in Chinese), and VIP (in Chinese) were searched for randomized controlled trials in human beings with the search terms including "polycystic ovary syndrome /PCOS" and "berberine/BBR/Huang liansu (in Chinese)/ Xiao bojian (in Chinese)" till July 2018. Relevant indices were collected and analyzed by Stata 13.0. RESULTS: A total of 9 randomized controlled trials were included. Limited data demonstrated the results as follows: No significant difference was found between berberine (BBR) and metformin (MET) on alleviating insulin resistance, improving glycolipid metabolism, or reproductive endocrine condition. MET combined with BBR was not superior to MET alone, but cyproterone acetate (CPA) combined with BBR was superior to CPA alone in improving some of the reproductive endocrine indices. The combination of BBR and Chinese herbs also showed positive effect. However there are insufficient data to make any conclusions on the effect of BBR on PCOS-IR. CONCLUSION: BBR showed a promising prospect in treating PCOS-IR. But its mechanisms are still unclear, and more properly designed, randomized, double-blind, placebo-controlled trials are needed to further confirm its effect and safety.

[Effect of different concentrations of Gegen Qinlian decoction on expression of P-glycoprotein and multi-drug resistance protein transporter in Caco-2 cells].

To investigate the effects of Gegen Qinlian decoction on the expression of P-glycoprotein (P-gp) and multi-drug resistance protein (MRP) in epithelial cells of human colon adenocarcinoma Caco-2 cells．The effects of different concentrations of Gegen Qinlian decoction on the expression levels of p-gp and MRP1-6 mRNA in Caco-2 cells were detected by real time quantitative reverse transcriptase PCR (qRT-PCR).12 h after drug treatment (5.00 g·L⁻¹), the expression levels of MDR1 and MRP1-6 were significantly down-regulated at concentration of 5.00 g·L⁻¹; the mRNA expression levels of MDR1，MRP1，MRP2，MRP4，MRP5 and MRP6 were significantly down-regulated at concentration of 2.50 g·L⁻¹; only the expression levels of MRP2 and MRP5 were significantly affected at concentration of 1.00 g·L⁻¹. The results showed that the expression levels of MDR1 and MRP1-6 mRNA in Caco-2 cells could be down-regulated in a dose-dependent manner. Gegen Qinlian decoction may reduce drug efflux by down-regulating the mRNA expression of cell transporters in Caco-2 cell, and increase the time of drug action, thereby enhancing the bioavailability of chemotherapeutic drugs.

Bu-Shen-Yi-Qi formula impairs cytotoxicity of NK cells by up-regulating IDO expression in trophoblasts.

Recurrent spontaneous abortion (RSA) is a common health problem that affects about 5% of fertile women, when it occurs for unknown reasons, it is called unexplained recurrent spontaneous abortion (URSA). Traditional Chinese medicine, such as Bu-Shen-Yi-Qi formula which consists of Dangshen, Tusizi, Baizhu, Baishuo, Duzhong, Sangjisheng, Sugeng, and Tiaohuangqin, has played an invaluable role in the treatment of RSA since ancient times. However, the mechanism of how it takes effect is still not clear. To identify Bu-Shen-Yi-Qi formula could modulate immune condition at maternal-fetal interface via its effect on trophoblasts, HTR-8 of different treatment were co-cultured with peripheral or decidual natural killer (NK) cells, and the receptors such as NKP30 and NKP46 expression on NK cells were measured by flow cytometry (FCM). In this study, we found that herb medium could increase the IDO expression at appropriate concentrations. As an inhibitor of IDO, 1-MT could impair the inhibitory function of trophoblasts on NK cells. Furthermore, Bu-Shen-Yi-Qi formula could enhance the inhibitory function of trophoblasts on NK cells. In conclusion, Bu-Shen-Yi-Qi formula can inhibit NK cytotoxicity by up-regulating IDO expression in trophoblasts and play a role in the treatment of URSA patients.

[Study on biopharmaceutics classification system for Chinese materia medica of extract of Huanglian].

One of the advantages of biopharmaceutics classification system of Chinese materia medica (CMMBCS) is expanding the classification research level from single ingredient to multi-components of Chinese herb, and from multi-components research to holistic research of the Chinese materia medica. In present paper, the alkaloids of extract of huanglian were chosen as the main research object to explore their change rules in solubility and intestinal permeability of single-component and multi-components, and to determine the biopharmaceutical classification of extract of Huanglian from holistic level. The typical shake-flask method and HPLC were used to detect the solubility of single ingredient of alkaloids from extract of huanglian. The quantitative research of alkaloids in intestinal absorption was measured in single-pass intestinal perfusion experiment while permeability coefficient of extract of huanglian was calculated by self-defined weight coefficient method.

[Overall intestinal permeability of multiple components in lotus leaf by in situ single pass intestinal perfusion models].

To investigate the overall intestinal permeability of multiple components in lotus leaves and make clear the interaction in composition absorption process. Rat single-pass intestinal perfusion technique was used, and the results showed that the Peff values of nuciferine, demethylanuciferine, rutin, quercetin, kaempferol from lotus leaf were greater than 0.5×10⁻4 cm•s⁻¹. In the biopharmaceutics classification system (BCS) intestinal permeability property, these ingredients were high permeable components, while the hyperin was low permeable component. However, in the multi-component environment of the lotus leaf extract, component permeation was changed. Semi quantitative analysis of the unclear components showed that under the multi-component environment, four in seven components with relatively high contents had a Peff value less than 0.5×10⁻4 cm•s⁻¹, indicating these 4 components were of low permeability, while other 3 components were of high permeability. The results could be valuable to make clear the overall intestinal permeability of multiple components in lotus leaf, and lay a foundation for studying the mechanism of the lipid-lowering effect of lotus leaf.

[Validation of in situ single pass perfusion model based on P-gp].

To validate in situ rats intestinal single pass perfusion model based on P-glycoprotein (P-gp). Firstly, phenol red perfusion was carried out to verify the close connection structure of intestinal epithelial cells, and the integrity of the intestinal epithelium, with a gravimetric method for correcting water flux. The level of phenol red was determined by high performance liquid chromatography (HPLC) both before and after perfusion. Secondly, the positive drug digoxin specified by FDA was used to validate the model. After different mass concentrations of verapamil were given in the rats, the absorption parameters of digoxin in ileum of rats were observed and compared. The results showed that the phenol red was absorbed in rats ileum segment, with an effective permeability coefficient of (1.09±0.62)×10 ⁻6 cm•s ⁻¹. The experiment results indicated that the close connection structure of intestinal epithelial cells was normal, and the integrity of the intestinal epithelium was maintained well. In digoxin perfusion experiment, in case no verapamil was given, digoxin showed certain degree of absorption in rat ileum, with an effective permeability coefficient (Peff) of (1.07±0.59)×10 ⁻5 cm•s ⁻¹; after mass concentrations of 0.01,0.1 mmol•L ⁻¹ verapamil were given, the absorption of digoxin was on the rise in rat ileum, with an effective permeability coefficient Peff of (1.58±0.69)×10 ⁻5, (3.28±0.95)×10 ⁻5 cm•s ⁻¹ respectively (P<0.05). Digoxin perfusion experiment verified that P-gp expression in small intestine epithelium was intact and can be used in the research of P-gp efflux transporter.

[In vitro and in vivo intestinal absorption of Huanglian decoction in multi-component environment].

The effect of drugs in the body is always inseparable with the dynamic processes of absorption, distribution, metabolism and excretion. For oral drug, absorption, as the first link to enter the body, is particularly valued. Traditional Chinese medicine has multiple components and multiple targets, and the nature of its single composition is different from that in the multicomponent environment. Alkaloids in Huanglian extract was used as the main object in this study to establish an analytical method for determining the content of alkaloids in Huanglian. In addition, the compositions of the Huanglian aqueous extract solution which can be absorbed through intestinal wall into blood, were initially determined by the means of everted gut sac and in intestinal perfusion with venous sampling experiment. This paper can provide data reference and support for the further study on the absorption and metabolism of Huanglian.

A general description for Chinese medicine in treating premature ovarian failure.

Premature ovarian failure (POF) is a kind of gynecological disease that causes amenorrhea, infertility, menopause and urogenital symptoms. Currently hormone replacement therapy (HRT) is the most popular choice for women with POF to get rid of menopausal syndrome. However, as the popularization of Chinese herbs made Chinese medicine (CM) shine new lights, physicians are able to treat POF with both meno-herbs and integrated therapy. HRT has its own indications and contraindications. For example, unexplained vaginal bleeding, acute liver damage, liver dysfunction, vascular embolization, and breast cancer are all contraindications of HRT, and CM is taken by more physicians as an adjuvant therapy. This review, including a range of common Chinese herbs and formulations according to the existing literature, provides a general description of CM treating POF from the aspects of mechanisms and clinical application. It also highlights acupuncture as a unique physiotherapy for POF. Although the validity of CM has been supported by the evidence of many preclinical trials, clinical trials and meta-analysis, the adverse events with CM therapy still exist and no guarantee has been made for its safety. This review concludes the updated information for CM treating POF contributing to further studies.