This study explored the drying kinetics of Salviae Miltiorrhizae Radix et Rhizoma(SM), established the suitable models simulating the drying kinetics, and then analyzed the dynamic changes of active components during the drying processes with different methods, aiming to provide a basis for the establishment of suitable drying methods and the quality control of SM. The drying kinetics were studied based on the drying curve, drying rate, moisture effective diffusion coefficient, and drying activation energy, and the appropriate drying kinetics model of SM was established. The drying performance of different methods, such as hot air drying, infrared drying, and microwave drying of SM was evaluated, and the changes in the content of 10 salvianolic acids and 6 tanshinones during drying were analyzed by UPLC-TQ-MS. The Technique for Order Preference by Similarity to an Ideal Solution(TOPSIS) was employed to evaluate the quality of SM dried with different methods. The results showed that the drying rate and moisture effective diffusion coefficient of SM increased with the rise in drying temperature, and the maximum drying rates of different methods were in the order of microwave drying > infrared drying > hot air drying, slice > whole root. The drying rate decreased with the rise in temperature and the extension of drying time. The activation energy of hot air drying was higher than that of infrared drying in SM. The most suitable model for simulating the drying process of SM was the Page model. The TOPSIS results suggested infrared drying at 50 ℃ was the optimal drying method for SM. During the drying process, the content of salvianolic acids increased in different degrees with the loss of moisture, among which salvianolic acid B showed the largest increase of 44 times compared with that in the fresh medicinal material. Tanshinones also existed in the fresh herb of SM, and the content of tanshinone Ⅱ_A increased by 3 times after drying. The results provided a basis for the establishment of suitable drying methods and the quality control of SM.

ETHNOPHARMACOLOGICAL RELEVANCE:The fruit of Lycium barbarum L. (goji berry) is a traditional Chinese medicine and is often used to improve vision. While various goji cultivars may differentially treat retinal degeneration, however their comparative effectiveness remains unclear.AIM OF THE STUDY:To evaluate the protective effects of four goji cultivars on NaIO3-induced retinal degeneration mouse model and identify the most therapeutically potent cultivar.MATERIALS AND METHODS:The principal compounds in the extracts of four goji cultivars were characterized by UPLC-Q-TOF/MS. A retinal degeneration mouse model was established via NaIO3 injection. Dark-light transition and TUNEL assays were used to assess visual function and retinal apoptosis. The levels of antioxidative, inflammatory, and angiogenic markers in serums and eyeballs were measured. Hierarchical cluster analysis, principal component analysis and partial least squares-discriminant analysis were used to objectively compare the treatment responses.RESULTS:Sixteen compounds were identified in goji berry extracts. All goji berry extracts could reverse NaIO3-induced visual impairment, retinal damage and apoptosis. The samples from the cultivar of Ningqi No.1 significantly modulated oxidative stress, inflammation, and vascular endothelial growth factor levels, which are more effectively than the other cultivars based on integrated multivariate profiling.CONCLUSION:Ningqi No.1 demonstrated a stronger protective effect on mouse retina than other goji cultivars, and is a potential variety for further research on the treatment of retinal degeneration.

ETHNOPHARMACOLOGICAL RELEVANCE:Bufei Huoxue capsule (BHC) as a classic Chinese patent medicine formula, has the efficacy of tonifying the lungs and activating the blood. It has been extensively used in China for the treatment of chronic obstructive pulmonary disease (COPD) clinically. However, its mechanism is still unclear, which hampers the applications of BHC in treating COPD.AIM OF THE STUDY:The purpose of the present study was to demonstrate the protective efficacy and mechanism of BHC on COPD model rats by integrating serum metabolomics analysis and network pharmacology study.MATERIALS AND METHODS:A COPD rat model was established by cigarette fumigation combined with lipopolysaccharide (LPS) airway drip for 90 consecutive days. After oral administration for 30 days, the rats were placed in the body tracing box of the EMKA Small Animal Noninvasive Lung Function Test System to determine lung function related indexes. Histopathological alteration was observed by H&E staining and Masson staining. The serum levels of inflammatory cytokine, matrix metalloprotein 9, and laminin were determined by ELISA kits. Oxidative stress levels were tested by biochemical methods. UHPLC-Q-TOF/MS analysis of serum metabolomics and network pharmacology were performed to reveal the bioactive metabolites, key components and pathways for BHC treating COPD. WB and ELISA kits were used to verify the effects of BHC on key pathway.RESULTS:BHC could improve lung function, immunity, lung histopathological changes and collagen deposition in COPD model rats. It also could significantly reduce inflammatory response in vivo, regulate oxidative stress level, reduce laminin content, and regulate protease-antiprotease balance. Metabolomics analysis found 46 biomarkers of COPD, of which BHC significantly improved the levels of 23 differential metabolites including arachidonic acid, leukotriene B4 and prostaglandin E2. Combined with the results of network pharmacology, the components of BHC, such as calycosin, oxypaeoniflora, (S)-bavachin and neobavaisoflavone could play therapeutic roles through the arachidonic acid pathway. In addition, the results of WB and ELISA indicated that BHC could suppress the expressions of COX2 and 5-LOX in lung tissues and inhibit the generation of AA and its metabolites in serum samples. Regulation of arachidonic acid metabolic pathway may be the crucial mechanism for BHC treating COPD.CONCLUSIONS:In summary, the studies indicated that BHC exhibited the protective effect on COPD model rats by anti-inflammatory and anti-oxidative properties through arachidonic acid metabolism pathway. This study provided beneficial support for the applications of BHC in treating COPD.

Lycium barbarum polysaccharides (LBPs) are recognized as key bioactive constituents of Lycium barbarum with diverse biological activities. However, current research on LBPs is largely confined to crude extracts, offering limited insight into the structural properties underlying their biological effects. In this study, we separated crude LBP into acidic LBP (ALBP) and neutral LBP (NLBP), which exhibited distinct physicochemical properties. ALBP, consisting of 76.18 % galacturonic acid (GalA), demonstrated crystallinity, thermal stability and gelatinous characteristics. In contrast, NLBP, with only 3.16 % GalA, displayed a more porous structure and superior fluidity. Furthermore, functional analysis revealed that NLBP exhibited enhanced immunoregulatory effects by activating dendritic cells and repolarizing macrophages. In a B16F10 melanoma-bearing C57BL/6 J mice model, NLBP significantly inhibited tumor growth with an inhibition rate of 66.7 % through macrophage repolarization. The findings highlight the distinct biological effects of NLBP and ALBP, providing a theoretical foundation for the refined utilization of LBP.

The multivariate statistical analysis was performed to compare the therapeutic effects of Lycii Fructus from different origins on the retinal degenerative diseases(RDD)in mice.The mouse model of RDD was established by intraperitoneal injection of NaIO3,and the visual function and retinal apoptosis were assessed by dark-light transition and TUNEL assay.Retinal thickness was measured by fundus optical coherence tomography(OCT),and the levels of antioxidant,inflammatory,and angiogenic markers in the serum and eyeball were determined.The therapeutic effects were compared by hierarchical cluster analysis,principal component analysis,and partial least squares-discriminant analysis.The results showed that the extracts of Lycii Fructus from different origins reversed NaIO3-induced visual damage and retinal apoptosis,reduced oxidative stress,and restored the expression of inflammatory mediators and angiogenic markers in mice.The multivariate statistical analysis based on 17 pharmacodynamic indices suggested that the extract of Lycii Fructus from Ningxia demonstrated better therapeutic effects on RDD than the samples from the other four origins.The results of this study provide a scientific basis for the selection of the advantageous production region of Lycii Fructus for the prevention and treatment of RDD.

目的 通过数据挖掘含姜-枣药对的方剂信息,分析其配伍特点及组方规律,为临床合理应用及药物开发提供指导.方法 检索含姜-枣药对的方剂数据,采用Excel软件提取方药信息,并运用R语言、Cytoscape软件对方剂组成、剂量、配比、功效、病证等进行频次统计及关联分析.结果 共检索到847首含姜-枣药对的方剂,涉及中药475种,使用频次9786次,常用药对为生姜-大枣和干姜-大枣,其次为炮姜-大枣、煨姜-大枣、姜炭-大枣.目标方剂共涉及19种功效及63种病证,其中功效以补益、和解应用最为频繁,且生姜-大枣侧重于解表,干姜-大枣侧重于温里;病证以内科病证为首,主要为虚劳、腹痛、感冒等.大枣每人日服量集中于20枚以下,与补益、和解、解表等关联较强;生姜每人日服量主要为＜20 g,与和解、解表相关联;干姜每人日服量主要为＜5 g,与温里、和解相关联.生姜-大枣配比以＞1为主,与补益、安神、和解相关联;干姜-大枣用于补益、安神时配比＜1,用于和解时配比≥1.与生姜-大枣、干姜-大枣高频配伍的药物组成相近,均有甘草、人参、白芍、茯苓等药味;核心药物组成有所不同,与生姜-大枣相关的核心药物组成为生姜-大枣-甘草-人参、生姜-大枣-白芍-甘草,与干姜-大枣相关的核心药物组成为干姜-大枣-甘草-人参、干姜-大枣-当归-甘草、干姜-大枣-甘草-肉桂、干姜-大枣-茯苓-甘草.结论 含姜-枣药对方剂功效以补益、和解为主,针对不同疾病姜-枣的剂量和配比需适当调整,与姜-枣药对配伍的高频药物主要为甘草、人参、白芍、茯苓.

Ethnopharmacological relevance: Xianlian jiedu decoction (XLJDD) is an effective traditional Chinese medicine formula that has been used in the treatment of colorectal cancer (CRC) for several decades. But now it still has an incomplete understanding of the role of XLJDD in colorectal cancer.Aim of the studyThis study aimed to evaluate the anti-tumor effect of XLJDD on CT-26 tumor-bearing mice, explore its possible mechanism and analyze the potential active ingredients.Materials and methods: In vivo, the anti-cancer effects of XLJDD and its active factions was evaluated by established xenograft model of colorectal cancer in BALB/C mice. Tumor suppressive effect was assessed by observing tumor growth. The pathomorphology of tumor tissue was observed by H&E staining. TUNEL staining was used to observe the apoptosis of cells in tumor tissues. The percentages of CD3+, CD4+ and CD8+ T lymphocytes in peripheral blood of mice were determined by flow cytometry. The levels of TNF-α, IL-1β and IL-2 in serum of mice were measured by ELISA. The expression of Caspase-3, Ki67 and PTEN protein in tumor tissue was detected by immunohistochemistry. RT-PCR was used to determine the expression of PI3K, PTEN, AKT and FOXO3A mRNA, and Western blotting was used to determine the expression of PI3K, PTEN, AKT and FOXO3A protein. Quantitative analysis of diverse extracted parts of XLJDD were carried out by UPLC-TQ/MS.Results: It was suggested that XLJDD and its active fractions could inhibit the growth of solid tumor, promote pathological damage to tumor tissues, and induce apoptosis. An increase in CD3+ and CD4+ T lymphocytes was observed in peripheral blood, along with a decrease in CD8+ T lymphocytes. Treatment with XLJDD and its different fractions decreased the expression of inflammatory cytokines (including IL-1β, IL-2 and TNF-α) in the serum. At the same time, in the tumor tissue, the expression of Caspase-3 and PTEN protein were up-regulated, while the expression of Ki67 protein was down regulated. This may be related to the activation of PTEN/PI3K/AKT/FOXO3A signaling pathway.Conclusion: In conclusion, these results demonstrated that XLJDD could exert anti-tumor effect in CT-26 tumor-bearing mice by reducing inflammatory reaction, strengthening immunity, promoting tumor cell apoptosis and inhibiting tumor cell proliferation through PTEN/PI3K/AKT/FOXO3A signal pathway. This may be mainly related to the bioactive components of berberine, coptisine, matrine and oxymatrine.

Xiexin Tang (XXT) is a classic prescription for treating diabetes in clinical practices for thousands of years in China, which has been also proved by a large number of modern pharmacological studies. However, due to its complex composition, the bioactive ingredients of XXT is still unclear. In present researches, spectrum-effect relationship analysis is widely used to explore the material basis of traditional medical herbs, so this method was adopted in this study. Firstly, the extract of XXT was separated and enriched into 5 fractions by macroporous adsorption resin. Then, UPLC-Q-TOF/MS method was used for qualitative identification of components in each eluting part, and efficacy of each fraction was assessed by the T2DM rat model. Based on grey relational analysis and pearson bivariate correlation analysis, it was found that the components such as berberine, gallic acid, catechin, epicatechin, acteoside, berberastine and 1-O-galloyl-β-D-glucose might be the main effective basis of XXT to improve T2DM.

Polysaccharides are the most important effective components of Lycii fructus, which has a variety of biological activities and broad application prospects in the fields of medicine and food. In this study, we reported a novel arabinogalactan LFP-80-W1 with potential immunostimulatory activity. LFP-80-W1 was a continuous symmetrical single-peak with an average molecular weight of 4.58 × 104 Da and was mainly composed of arabinose and galactose. Oligosaccharide sequencing analyses and NMR data showed that the LFP-80-W1 domain consists of a repeated 1,6-linked β-Galp main chain with branches arabinoglycan and arabinogalactan at position C-3. Importantly, we found that LFP-80-W1 could activate the MAPK pathway and promote the release of NO, IL-6, and TNF-α cytokines in vitro. Therefore, our findings suggest that the homogeneous arabinogalactan from Lycii fructus, can be used as a natural immunomodulator.

目的 研究补肺活血胶囊(Bufei Huoxue Capsules,BHC)在大鼠血浆、胆汁、尿液、粪便中的原型成分及其代谢产物,归纳总结不同类型化合物的体内代谢规律.方法 大鼠igBHC后,收集血浆、胆汁、尿液和粪便样品并进行预处理,采用超高效液相色谱-飞行时间质谱(ultra-high performance liquid chromatography-time-of-flight mass spectrometry,UPLC-Q-TOF-MS)及质量亏损过滤技术,分别在正、负离子模式下对原型成分及代谢产物进行分析鉴定.结果 共检测到没食子酸、芍药苷、毛蕊异黄酮、新补骨脂异黄酮、(S)-异补骨脂二氢黄酮、补骨脂苷等原型成分及代谢产物67个,其中酚酸类成分10个、单萜类成分7个、黄酮类成分35个、香豆素类成分12个、皂苷类成分3个,主要代谢途径包括氧化、还原、甲基化、葡糖醛酸结合、硫酸结合等.结论 初步阐明了 BHC大鼠体内的代谢产物及其代谢转化特征,为基于体内过程揭示其药效物质基础奠定了基础,为其临床安全用药提供了科学依据.

Huoluo Xiaoling Dan is a classical prescription commonly used for blood circulation and pain relief in clinic with obvious effects. To make it directly treat lesion and improve the effect, this research optimized the preparation process of Huoluo Xiaoling gel paste and further evaluated its in vitro transdermal absorption performance, so as to provide a scientific basis for its development and utilization. Using primary viscosity, holding viscosity, and sensory score as evaluation indexes, the matrix amount of gel paste was determined by the single factor test and Box-Behnken response surface method. The ultra-performance liquid chromatography(UPLC) method was established to determine the content of eight active ingredients, including Danshensu, ferulic acid, salvianolic acid B, salvianolic acid A, ligustilide, tanshinone Ⅱ_A, 11-keto-β-boswellic(KBA), and 3-acetyl-11-keto-β-boswellic acid(AKBA). A mo-dified Franz diffusion cell method was used to evaluate and compare the absorption properties of the gel paste without volatile oil and with volatile oil microemulsion. The results showed that the optimal prescription for Huoluo Xiaoling gel paste matrix was NP700(1.35 g), glycerol(7.00 g), micropowder silica gel(1.25 g), sodium carboxymethyl cellulose(0.20 g), tartaric acid(0.06 g), and glyceryl aluminum(0.04 g). The mass fractions of eight active ingredients in the paste were successively 0.48, 0.014, 0.95, 0.39, 0.57, 0.055, 0.35, and 0.97 mg·g~(-1). The results of the in vitro transdermal absorption test showed that the addition of the volatile oil or the volatile oil microemulsion promoted the transdermal absorption of the active ingredients, and the law of drug penetration conformed to the zero equation or the Higuchi equation. The gel paste prepared by the optimal prescription has good appearance and adhesion, with no residue, and has the characteristics of skeletal slow-release preparation, which is easy to reduce the number of administration, la-ying a foundation for the development of new external dosage forms of Huoluo Xiaoling Dan.

OBJECTIVE To evaluate the effect and mechanism of Qili Huanshao Formula(QLHSF)in ameliorating sex hormone disturbance and oxidative damage in testicular tissues of D-galactose-induced subacute aging mice.METHODS 105 male mice were randomly divided into the normal group,model group,low,medium and high doses of QLHSF group,vitamin E(VE)group and Jin Gui Shen Qi Wan(JGSQW)group.The subacute senescence model was established by continuous intraperitoneal injection of D-galac-tose(D-gal)and treated by intragastric administration,as well.The testicular histopathological damage was detected by HE staining.The levels of relevant sex hormones in serum were detected by ELISA.The expression of oxidative stress factors was detected by related kits.The apoptotic cells in testicular tissue were detected by TUNEL assay,and the expressions of oxidative stress and apop-totic related proteins in the testicular tissues of mice were detected by Western blot.RESULTS Compared to the aging model mice,all dose groups of QLHSF could obviously improve testicular tissue pathological damage.The levels of T,E2 and GnRH levels were in-creased,while LH and FSH were decreased in serum(P<0.01).Meanwhile,the SOD activity(P<0.01)and the levels of GSH(P<0.01)were increased,while MDA levels(P<0.01)were decreased in serum and testicular tissues.The medium dose group of QLHSF significantly inhibited testicular cell apoptosis(P<0.01),increased the expression of Nrf2,HO-1 protein and Bcl-2/Bax ratio(P<0.05),and down-regulated the expressions of Cleaved-Caspase-3/Caspase-3,Cleaved-Caspase-9/Caspase-9 apoptotic protein in the testis of mice(P<0.05).CONCLUSION QLHSF can effectively improve sex hormone disturbance and protect testicular tissue in aging mice,and the mechanism of action might be related to the inhibition of oxidative stress-induced apoptosis in testicular tissues.The study will provide reference and lay the foundation for the clinical application and functional anti-aging product develop-ment of Lycium barbarum and its formulations.

As a traditional Chinese herb and functional food, the fruits of Lycium barbarum has been widely used for thousands of years in China. L. barbarum polysaccharides(LBPs) are predominant active components, which have immunomodulatory, antioxidant, hypoglycemic, neuroprotective, anti-tumor, and prebiotic activities. The molecular weight, monosaccharide composition, glycosidic bond, branching degree, protein content, chemical modification, and spatial structure of LBPs are closely related to their biological activity. Based on the previous studies of this research team, this paper systematically combed and integrated the research progress of structure, function, and structure-activity relationship of LBPs. At the same time, some problems restricting the clarification of the structure-activity relationship of LBPs were considered and prospected, hoping to provide references for the high value utilization of LBPs and in-depth exploration of their health value.

目的 利用荧光标记辅助的扩增片段长度多态性(amplified fragment length polymorphism,AFLP)技术,从基因组DNA水平上分析我国6个栽培生产区域52份枸杞Lycium chinense样本的遗传多样性.方法 对提取的枸杞DNA样本进行酶切、连接、预扩增和选扩增等步骤,扩增产物经毛细管电泳系统分离和数据采集后,利用Popgene软件计算遗传多样性参数,利用GenAlex软件计算遗传距离并进行主坐标分析,利用MEGA-X软件根据遗传距离进行聚类分析,利用Structure软件进行群体遗传结构分析.结果 共筛选得到10对AFLP选择性扩增引物组合,扩增得到328条扩增片段,其中多态性片段121条,且在不同产地枸杞居群间多态性位点分布不均匀.分析显示不同栽培产区枸杞的遗传多样性较低,等位基因数(observed number of alleles,Na)、有效等位基因数(effective number of alleles,Ne)、观测杂合度(Nei's gene diversity,H)和香浓信息指数(Shannon information index,I)分别为 1.438 0、1.231 6、0.140 7 和 0.215 2,Nei's 遗传相似性范围为0.835 4～0.890 2.结论 不同栽培生产区域的枸杞居群间存在较为频繁的基因交流,遗传分化程度中等.居群内部遗传变异是枸杞遗传变异的主要来源,居群间遗传变异不显著,同时遗传距离与地理距离没有明显相关性.可为枸杞的遗传背景信息积累、引种栽培、种质资源保护、核心种质库构建以及可持续开发策略的制定和管理提供科学依据.

Background: 3-acetyl-11-keto-beta-boswellic acid (AKBA) and 11-keto-boswellic acid (KBA) are the main active components of frankincense as pentacyclic triterpenoids, which are designated by the European Pharmacopoeia 8.0 as the quality standard for the evaluation of Indian frankincense, 2-methoxy-8,12-epoxygermacra- 1(10),7,11-trien-6-one (MCS134) is a non-volatile sesquiterpene compound in myrrh. Objective: In this paper, the absorption pharmacokinetics and metabolites of AKBA, KBA and MCS134 after frankincense, myrrh and their compatibility were analyzed, elaborated their absorption and metabolism mechanism and provided the ideas for the research on the bioactive components of frankincense and myrrh compatibility in vivo. Methods: The area under the blood concentration time curve (AUC), half-life (t1/2) and drug clearance (CL) of AKBA, KBA and MCS134 in rats were analyzed by LC-TQ / MS. The metabolites of AKBA, KBA and MCS134 in rats were analyzed by ultra-high pressure liquid chromatography with a linear ion trap-high resolution Orbitrap mass spectrometry system (UHPLC-LTQ-Orbitrap-MS). Results: The results showed that AKBA, KBA and MCS134 reached the maximum plasma concentration at about 2 h, 2 h and 15 min, respectively. AUC0-t and t1/2 of the three components increased in varying degrees after compatibility, and the clearance/ bioavailability (CL/F) decreased. AKBA, KBA and MCS134 were metabolized in phase I and phase II in rats, and there represented differences before and after compatibility. Conclusion: After the compatibility of frankincense and myrrh, the absorption of effective components was improved to some extent, and there were some differences in the metabolites in rats. The results provide ideas for elucidating the in vivo effect mechanism of frankincense and myrrh.

Zingiber officinale and Panax ginseng, as well-known traditional Chinese medicines, have been used together to clinically treat ulcerative colitis with synergistic effects for thousands of years. However, their compatibility mechanism remains unclear. In this study, the shift of gut microbiome and fecal metabolic profiles were monitored by 16S rRNA sequencing technology and ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry analysis, respectively, which aimed to reveal the synergistic mechanism of Zingiber officinale and Panax ginseng on the amelioration of ulcerative colitis. The results showed that the relative abundance of beneficial bacteria (such as Muribaculaceae_norank, Lachnospiraceae NK4A136 group and Akkermansia) was significantly increased and the abundance of pathogenic bacteria (such as Bacteroides, Parabacteroides and Desulfovibrio) was markedly decreased after the intervention of Zingiber officinale-Panax ginseng herb pair. And a total of 16 differential metabolites related to ulcerative colitis were identified by the metabolomics analysis, which were majorly associated with the metabolic pathways, including arachidonic acid metabolism, tryptophan metabolism, and steroid biosynthesis. Based on these findings, it was suggested that the regulation of the gut microbiota-metabolite axis might be a potential target for the synergistic mechanism of Zingiber officinale-Panax ginseng herb pair in the treatment of ulcerative colitis. Furthermore, the integrated analysis of microbiome and metabolomics used in this study could also serve as a useful template for exploring the mechanism of other drugs.

目的 建立超高效液相色谱法(UHPLC)同时测定补肺活血胶囊(Bufei Huoxue Capsules,BHC)中12种指标成分没食子酸、氧化芍药苷、芍药内酯苷、补骨脂苷、芍药苷、异补骨脂苷、毛蕊异黄酮苷、芒柄花苷、毛蕊异黄酮、补骨脂素、异补骨脂素、苯甲酰芍药苷的含量.方法 采用AcquityUPLCBEHC18色谱柱(100 mm×2.1 mm,1.7 μm);流动相为乙腈-0.1％甲酸水溶液,梯度洗脱;体积流量0.4mL/min,柱温35℃,进样量4μL,检测波长246 nm.结果 BHC中12种指标成分在18 min内色谱峰分离良好,没食子酸、氧化芍药苷、芍药内酯苷、补骨脂苷、芍药苷、异补骨脂苷、毛蕊异黄酮苷、芒柄花苷、毛蕊异黄酮、补骨脂素、异补骨脂素和苯甲酰芍药苷分别在0.38～195.20(r=0.999 9)、0.17～21.44(r=0.999 6)、0.85～433.80(r=0.999 9)、0.68～345.60(r=0.999 9)、1.11～566.60(r=0.999 8)、0.47～241.40(r=0.999 9)、0.08～39.36(r=0.999 8)、0.05～26.16(r=0.999 9)、0.03～16.42(r=0.999 9)、0.25～129.10(r=0.999 8)、0.26～133.10(r=0.999 7)、0.09～47.28 μg/mL(r=0.999 9)线性关系良好;精密度、稳定性、重复性、加样回收率均符合分析要求.11批补肺活血胶囊中没食子酸、氧化芍药苷、芍药内酯苷、补骨脂苷、芍药苷、异补骨脂苷、毛蕊异黄酮苷、芒柄花苷、毛蕊异黄酮、补骨脂素、异补骨脂素和苯甲酰芍药苷平均质量分数分别为2.6242、0.222 4、16.409 9、7.459 5、18.9742、7.887 5、0.505 7、0.109 9、0.170 7、1.364 7、1.170 0、0.203 6 mg/g.结论 所建立的方法分析速度快、准确度高、重复性好,为BHC质量标准提升提供了方法支撑.

Rhubarb, a traditional herb, has been used in clinical practice for hundreds of years to cure constipation, but its mechanism is still not clear enough. Currently, growing evidence suggests that intestinal flora might be a potential target for the treatment of constipation. Thus, the aim of this study was to clarify the laxative effect of rhubarb via systematically analyzing the metagenome and metabolome of the gut microbiota. In this study, the laxative effects of rhubarb were investigated by loperamide-induced constipation in rats. The gut microbiota was determined by high-throughput sequencing of 16S rRNA gene. Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for fecal metabolomics analysis. The data showed that rhubarb could significantly shorten gastrointestinal transit time, increase fecal water content and defecation frequency, improve gastrointestinal hormone disruption, and protect the colon mucus layer. Analysis of 16S rRNA gene sequencing indicated that rhubarb could improve the disorder of intestinal microbiota in constipated rats. For example, beneficial bacteria such as Ligilactobacillus, Limosilalactobacillus, and Prevotellaceae UCG-001 were remarkably increased, and pathogens such as Escherichia-Shigella were significantly decreased after rhubarb treatment. Additionally, the fecal metabolic profiles of constipated rats were improved by rhubarb. After rhubarb treatment, metabolites such as chenodeoxycholic acid, cholic acid, prostaglandin F2α, and α-linolenic acid were markedly increased in constipation rats; in contrast, the metabolites such as lithocholic acid, calcidiol, and 10-hydroxystearic acid were notably reduced in constipation rats. Moreover, correlation analysis indicated a close relationship between intestinal flora, fecal metabolites, and biochemical indices associated with constipation. In conclusion, the amelioration of rhubarb in constipation might modulate the intestinal microflora and its metabolism. Moreover, the application of fecal metabolomics could provide a new strategy to uncover the mechanism of herbal medicines. Key points • Rhubarb could significantly improve gut microbiota disorder in constipation rats. • Rhubarb could markedly modulate the fecal metabolite profile of constipated rats.

目的 研究复方蜥蜴散在大鼠体内的代谢产物.方法 大鼠ig复方蜥蜴散后,收集并处理血浆、胆汁、尿液、粪便,采用UHPLC-LTQ-Orbitrap-MS方法以及质量亏损过滤技术分析主要成分代谢产物.结果 建立了复方蜥蜴散代谢产物分析方法,共鉴定出芒柄花素、毛蕊异黄酮、延胡索乙素等8个原型成分和31个代谢产物.结论 复方蜥蜴散主要成分在大鼠体内主要发生去甲基化、羟基化、还原反应等I相反应,硫酸化、葡萄糖醛酸化等II相反应,所建立的方法简单可靠.为进一步阐明复方蜥蜴散药效物质基础,优化临床给药方案提供依据.

Ulcerative colitis (UC), an etiologically complicated and relapsing gastrointestinal disease, is characterized by the damage of mucosal epithelium and destruction of the intestinal homeostasis, which has caused a huge social and economic burden on the health system all over the world. Its pathogenesis is multifactorial, including environmental factors, genetic susceptibility, epithelial barrier defect, symbiotic flora imbalance, and dysregulated immune response. Thus far, although immune cells have become the focus of most research, it is increasingly clear that intestinal epithelial cells play an important role in the pathogenesis and progression of UC. Notably, apoptosis is a vital catabolic process in cells, which is crucial to maintain the stability of intestinal environment and regulate intestinal ecology. In this review, the mechanism of apoptosis induced by reactive oxygen species and endoplasmic reticulum stress, as well as excessive apoptosis in intestinal epithelial dysfunction and gut microbiology imbalance are systematically and comprehensively summarized. Further understanding the role of apoptosis in the pathogenesis of UC may provide a novel strategy for its therapy in clinical practices and the development of new drugs.