查找使用阿拉丁产品的科研文献

High accuracy prediction of dipeptide angiotensin-converting enzyme (ACE) inhibitory activity by improving the credibility of the 3D-quantitative structure-activity relationship (3D-QSAR) model database and investigating inhibition mechanism

Qi Liu,Shan Shao,Jingyu Bao,Syed Jalil Shah,Shumin Yue,Xinqi Luan,Qing Liu,Linguang Xing,Zhongfeng Shi,Zhenxia Zhao,Zhongxing Zhao

The 3D-QSAR model is one of the most effective techniques for predicting the peptide bioactivity based on their structure properties. The accuracy of model prediction is highly dependent on the bio-activity of the peptides in its dataset. However, the same peptide used for constructing the database was reported to have obviously different activities in different published articles, which may significantly decrease the prediction accuracy. Based on this, we chose ACE inhibitory (ACE-I) dipeptides that can be absorbed directly into the human small intestine as research object. Ten dipeptides were randomly selected from the literatures for molecular docking with ACE and synthesized to test their activity. Ultimately, a linear equation was developed between bio-activities and docking scores, which was used to revalidate the reliable ACE-I activities of all reported dipeptides for constructing a credible dataset of 3D-QSAR model. The prediction accuracy was significantly enhanced and the model we established had a high Q 2 = 0.840 and R 2 = 0.998. Furthermore, dipeptide CW was predicted and tested in vitro to achieve the highest ACE-I activity (IC 50 = 0.16 μM), and the inhibition mechanism was also investigated. This study introduced a new method for predicting bio-activity with high precision using the 3D-QSAR model.

Oral absorption mechanism of the polysaccharides from Gastrodia elata Blume base on fluorescence labeling

Baiyu Zhang,Mengmeng Liu,Gang Liu,Dan Li,Benhong Zhou

The mechanisms of action of polysaccharides in vivo have been widely elucidated. However, the systematic research of its absorption and transport mechanisms remains unclear. Herein, we extracted a polysaccharide fraction (GEP) from Gastrodia elata by water extraction and alcohol precipitation and aimed to reveal its oral absorption processes through animal models and Caco-2 cells monolayer models. Our research data showed that GEP-Cy5.5 could be absorbed through the small intestine and the main absorption intestinal segment was the ileum (the absorption rate constant [Ka]: (3.64 ± 0.70) × 10 −4 cm/s; the effective apparent permeability [Papp value]: (4.88 ± 1.02) × 10 −5 cm/s). The ligated intestinal loops also revealed that GEP-Cy5.5 could pass through the villi of the small intestine and the mucosal barrier into the submucosa. Furthermore, GEP-Cy5.5 was readily absorbed into the blood through the gastrointestinal tract, then distributed in the liver and the kidney. The Papp value of in vitro transport study was (1.29 ± 0.08) × 10 −6 cm/s, which was a time-dependent process. Notably, GEP-Cy5.5 was transported through the endocytosis process mediated by clathrin and macropinocytosis. The underlying absorptive mechanisms of GEP in vivo and in vitro were clarified, which provided the guidance for clinical medicine administration and could deepen the biological understanding of oral polysaccharides.

Mucus Barrier Weakens the Inhibitory Activity of Pyrogallol-Based Polyphenols Against α-Glucosidase

Yi Wang,Suqing Lan,Laiming Zhang,Yunxuan Li,Ziyang Deng,Xingqian Ye,Haibo Pan,Shiguo Chen

Scope: Polyphenols reportedly possess strong in vitro α-glucosidase inhibitory activity, even higher than acarbose, but their in vivo regulation on postprandial hyperglycemia is poor. So far this typical problem of polyphenols remains unsolved, greatly hindering their application as α-glucosidase inhibitors. Methods and results: Here, we identify the small intestinal mucus layer acts as a barrier to significantly reduce in vivo α-glucosidase inhibitory activity of epigallocatechin gallate, prodelphinidin B digallate (proDB DG), and proanthocyanidins from Chinese bayberry leaves. Multispectroscopy, rheology, solvent method, and molecular docking analysis showed that these pyrogallol-based polyphenols, especially proDB DG strongly interacted with small intestinal mucins through hydrogen bonding, hydrophobic interactions, and electrostatic interactions. These interactions block polyphenols from penetrating the mucus layer, resulting in their low binding rates with α-glucosidase in vivo. Besides, polyphenol-driven aggregation of the mucins enhanced the barrier function and reduced the permeability of the mucus layer, resulting in delayed digestion and absorption of carbohydrates. Conclusions: The mucus barrier weakens the inhibitory activity of pyrogallol-based polyphenols against α-glucosidase. Hence, overcoming the mucus barrier is a promising strategy to improve the regulation of pyrogallol-based polyphenols against postprandial hyperglycemia in vivo, which helps them to become novel α-glucosidase inhibitors in the clinic.

Modulatory effects of taurine on jejunal contractility

Yao Q.Y.,Chen D.P.,Ye D.M.,Diao Y.P.,Lin Y.

Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.

Lotus seed resistant starch and sodium lactate regulate small intestinal microflora and metabolite to reduce blood lipid

Lu Liu,Suzhen Lei,Xiaoli Lin,Junfu Ji,Yanbo Wang,Baodong Zheng,Yi Zhang,Hongliang Zeng

Permeation of Hydroxypropyl-Beta-Cyclodextrin and Its Inclusion Complex Through Mouse Small Intestine Determined by Spectrophotometry

Yang Ping,Luo Jinhua,Yan Shuo,Li Xiaohong,Yao Qian

Background: Cyclodextrins (CDs) are commonly used host molecules of inclusion complex. However, due to the lack of a sensitive determination method, the absorption process of CDs remains unclear. Objective: In this study, an oleuropein (OL) inclusion complex employing hydroxylpropyl-betacyclodextrin (HP-beta-CD) as host molecules was prepared and the formation of inclusion complex was ascertained by FT-IR and DSC. Spectrophotometry was established for the determination of HP-beta-CD, based on the fact that the absorbance of phenolphthalein (PP) decreased in the presence of HP-beta-CD. Methods: The assay conditions were optimized to augment the method sensitivity. Molecular docking was employed to verify the strong interaction between PP and HP-beta-CD. The permeation process of free HP-beta-CD, HP-beta-CD of OL inclusion complex, free OL, and OL in the inclusion complex, was examined using an in vitro mouse small intestine model. Results: Though HP-beta-CD possessed a hydrophilic outside shell, it could permeate through the mouse small intestine quickly with a cumulative permeating amount of over 90% in 2 h. Free HPbeta- CD, the host molecule HP-beta-CD, and guest molecule OL of the inclusion complex exhibited consistent permeating profiles across the mouse small intestine. Conclusion: The approach for the determination of HP-beta-CD was accurate and precise (%RSD=2.98).

Permeability-Enhancing and Protective Effect on Small Intestine of Punicic Acid in Different Forms and Their Nanoemulsions With Low Toxicity

Dongyan Duan,Hua Xie,Jiayi Jiang,Ping Yang,Zhiyuan Guo,Xiaoqiang Guo,Xingyu Chen,Qian Yao

Purpose Most absorption enhancers boost the oral absorption of drugs via increasing intestinal permeability. However, they often damage intestinal mucosa and induce inflammatory reactions. The aim of this study is to synthesize a new absorption enhancer, punicic acid ethyl ester (PAEE), with excellent absorption-prompting effect and low toxicity.Methods The structure of PAEE was confirmed by NMR, MS, IR and UV. Setting oleic acid (OA) as the control, the three forms of punicic acid (PA), ie, free PA, PAEE, and pomegranate seed oil, in which PA exists in the form of triglyceride, were formulated into nanoemulsions (NE). The stability, physiochemical properties of the oils and NE were compared. The permeation-enhancing effect was estimated by phenol red intestinal transport experiments. The potential damage on small intestines was assessed by biochemical assay and pathological section.Results Though the three forms of PA had various strength in enhancing intestinal permeability, the difference was not significant (p > 0.05). Moreover, the effect was notably stronger than that of OA (p < 0.05) and was inversely related to the density and required HLB value of the oils. Compared to the corresponding oils, the NE exhibited much weaker effect in prompting intestinal permeability. Oral administration of OA and OA NE for 10 d impaired intestinal mucosa and villi along with strong inflammatory reactions in the small intestines. In contrast, the oils from PA series and their NE did not induce obvious intestinal inflammation. PAEE and its NE hindered the release of cytokines and increased the ratio of intestinal villus length to crypt depth.Conclusion PAEE is a promising absorption enhancer with a strong permeability-prompting effect and mucosa-protecting capacity against intestinal inflammation. It provides a practical strategy to enhance the bioavailability of the drugs with poor biological membrane penetration.

Effects of isovalerate supplementation on morphology and functional gene expression of small intestine mucosa in pre- and post-weaned dairy calves

Q. Liu,C. Wang,Y. L Zhang,C. X. Pei,S. L Zhang,G. Guo,W. J. Huo,W. Z. Yang

The present study evaluated the effects of isovalerate supplementation on the development of the small intestinal mucosa in dairy calves. Forty-eight Chinese Holstein bull calves at 15 days of age and 45.1 ± 0.36 kg of body weight were assigned randomly to four groups. The treatments were control, low-isovalerate, moderate-isovalerate and high-isovalerate with 0, 3, 6 and 9 g isovalerate per calf per day, respectively. The study comprised 75 days with a 15-day adaptation period followed by a 60-day sampling period. Calves were weaned at 60 days of age. Six calves were chosen from each treatment at random and slaughtered at 30 and 90 days of age. The small intestine morphology and activities of amylase and trypsin improved significantly with increasing age. No interaction between treatments and age was observed. The small intestine length, mucosa layer thickness, villus height and crypt depth increased linearly with increasing isovalerate supplementation. However, the ratio of villus height to crypt depth was not affected by treatment. Activities of amylase and trypsin increased linearly. The lactase activity increased linearly during the 75-day period and for pre-weaned calves but was unaltered for post-weaned calves. The relative mRNA expressions of growth hormone receptor, insulin-like growth factor-1 receptor and sodium-glucose co-transporter-1 in the small intestine mucosa increased linearly, and a similar pattern was observed for the expression of peptide transporter-1 in the duodenum and proximal jejunum. The results suggested that small intestine development was promoted by isovalerate in a dose-dependent manner.

Use of a Novel, Reinforced, Low Immunogenic, Porcine Small Intestine Submucosa Patch to Repair a Supraspinatus Tendon Defect in a Rabbit Model

Xuancheng Zhang,Zhaoyi Fang,Eunshinae Cho,Kai Huang,Jinzhong Zhao,Jia Jiang,Xiaoqiao Huangfu

Background. Repairs of large to massive rotator cuff tears have a high failure rate. We investigated the efficacy of a novel, reinforced, low immunogenic, porcine small intestine submucosa (SIS) patch to repair a supraspinatus tendon defect in a rabbit model. We hypothesized that the histological and biomechanical results of SIS patch repair would be comparable with those of autologous fascia lata (FL) repair. Methods. The study mainly comprised two parts. First, the characteristics of the SIS patch were evaluated, including its micromorphology, mechanical properties, and immunogenic properties. Second, a supraspinatus tendon defect model was created in 36 rabbits (72 shoulders). The bilateral shoulders were randomly chosen to undergo repair using either a SIS patch (SIS group) or autologous FL (FL group). At 4, 8, and 12 weeks, histological analysis was performed using four shoulders from each group, and biomechanical tests were performed using eight shoulders from each group. Results. The SIS patch was a three-dimensional construct mainly composed of collagen fibers. The mean single and double suture retention loads of the SIS patch were 48.6 ± 5.8 N and 117.9 ± 2.7 N, respectively. The DNA content in the SIS patch was 53.9 ± 10.9 ng/mg dry weight. Both the histological score and ultimate load to failure increased in a time-dependent manner in both groups, with no significant differences between the SIS and FL groups at 12 weeks. Conclusion. Repair of a large supraspinatus tendon defect using a reinforced, low immunogenic, SIS patch achieves similar effects as autologous FL in a rabbit model. This novel patch might be useful to be employed as a structural tissue replacement in medical activities.

Decoding nattokinase efficacy: From digestion and absorption to lipid pathway modulation in high-fat diet-induced atherosclerosis

Yongjie Zhou,Zixin Fu,Peipei Dou,Chen Yu,Xianyou Dong,Hui Hong,Yongkang Luo,Yuqing Tan

Nattokinase (NK), an alkaline serine protease, is recognized for its cardiovascular benefits through the modulation of blood coagulation and fibrinolytic pathways. Atherosclerosis (AS), a primary cause of cardiovascular disease (CVD) worldwide, is responsive to dietary interventions. However, studies investigating NK’s digestion, absorption, and mechanisms in mitigating AS remain limited. This study evaluated the effects of high-dose NK treatment (H-NK, 900 FU/kg body weight) administered over six weeks in ApoE -/- mice, which resulted in significant reductions in atherosclerotic lesions. In vitro digestion simulations showed that 25.8% of NK’s enzymatic activity was retained post-digestion, and thrombolysis assays demonstrated a thrombolytic efficacy of 30%-40% at concentrations ≥ 5,000 μg/mL, regardless of clot age. Absorption experiments using a rat everted intestinal sac model revealed a small intestine absorption rate of 37.0%, with the absorbed peptides being predominantly hydrophobic, uncharged, and shorter than 10 amino acids. Proteomic analysis of mouse liver tissues identified that high-dose NK down-regulated PXDN (peroxidasin) and PNLIP (pancreatic lipase), proteins involved in promoting lipid oxidation, and intestinal lipid absorption. These proteomic changes enhanced lipid metabolism, reduced lipid peroxidation, and alleviated AS through the "Lipid and Atherosclerosis" pathway. Overall, this study provides a deeper understanding of NK’s biological activity and supports its potential as a novel dietary supplement for the management of CVD.

Dietary Rutin Ameliorates Nanoparticle Zinc Oxide-Induced Toxicity in Mice by Potentiating Antioxidant Defense Mechanisms

Xiaofang He,Longfei Ma,Jiaqi Zhang,Binbin Zhou,Shun Chen,Minhang Tu,Gentan Cai,Tian Wang,Chao Wang

In animal production, nanoparticulate zinc oxide exhibits synergistic antibacterial efficacy coupled with growth-promoting effects, positioning itself as a novel antibiotic alternative with enhanced biosafety profiles. However, its dose-dependent toxicity poses challenges.Objective:The experimental design sought to quantify the protective effects of dietary rutin against zinc-overload-induced damage.Methods:A zinc-overload murine model was established by giving high-dose ZnO nanoparticles (HZn, 5000 mg/kg/day) for 21 days. Mice were then fed rutin at doses of 300, 600, or 1200 mg/kg. Body weight, relative organ indexes, zinc concentrations, serum enzyme activities, and tissue-level indicators of apoptosis, autophagy, mitochondrial function, and antioxidant capacity were measured.Results:The results showed that rutin could not reverse HZn-induced body weight decline but improved relative organ indexes in liver and kidney. It alleviated HZn-induced cell damage and enhanced antioxidant capacity in jejunum and serum throughNrf2activation, without inhibiting HZn-induced zinc elevation.Conclusions:Rutin, especially at 600 mg/kg, can partially restore hepatic function and organ index and mitigate HZn-induced hepatic and jejunal injuries.

A Novel UBM/SIS Composite Biological Scaffold for 2-Year Abdominal Defect Repairing and Strength Recovery in Canine Model

Weidong Zhong,Jinshui Chen,Qifeng Xie,Wenyue Cheng,Meibiao Zhao,Yang Sun,Jing Dai,Jian Zhang

Biological scaffolds are widely utilized in hernia treatment due to their exceptional pro-regenerative properties, which mitigate scar formation. However, serious complications occurred, caused by inflammatory response, premature degradation, and mechanical failure. Consequently, improvements of the biological scaffold are necessary to mitigate these risks. In this study, a novel biological scaffold integrating basement membrane-containing urinary bladder matrix (UBM) and small intestinal submucosa (SIS) is developed, and its safety and effectiveness are assessed in comparison to a commercial SIS (c-SIS) scaffold. The introduction of UBM as top surface layers significantly promotes cell adhesion, facilitating rapid formation of isolated regeneration zone. Proteomic analysis has demonstrated a more efficient decellularization of the UBM/SIS scaffold, which subsequently mitigates inflammation in murine models, and promotes the polarization of macrophages toward the pro-healing M2 phenotype in a rat model of abdominal wall muscle defect. Furthermore, a two-year repair trial is conducted on a full-thickness abdominal wall muscle defect in canine model and confirmed that the UBM/SIS scaffold exhibits reduced seroma occurrences and enhanced tissue repair performances. Overall, the efficacy of this novel biological scaffold suggests its potential to minimize hernia recurrence in clinical practice and mitigate patient suffering from severe inflammatory responses.