Study on the effect and mechanism of Swertia mussotii Franch. in the treatment of primary biliary cholangitis based on bioinformatics and in vitro experiments

Background:Primary biliary cholangitis(PBC)is a chronic biliary autoimmune liver disease characterized by intrahepatic cholestasis.Swertia mussotii Franch.(SMF)is a Tibetan medicine with hepatoprotective and anti-inflammatory activities.In this study,the therapeutic effect and potential mechanisms of SMF on PBC were investigated by bioinformatics analysis and in vitro experimental validation,with the aim of promoting the progress of SMF and PBC research.Methods:We first explored the therapeutic effects and key targets of SMF on PBC using a network pharmacology approach,further screened the core targets using the GSE79850 dataset,and finally validated the results using molecular docking techniques and in vitro experiments.Results:By bioinformatics analysis,we identified core targets of SMF for PBC treatment(STAT3,JAK2,TNF-α,and IL-1β)and important signaling pathways:JAK-STAT,TNF,and PI3K-AKT.The molecular docking results showed that the significant components of SMF had good binding properties to the core targets.In vitro experiments showed that SMF extracts improved the extent of epithelial-mesenchymal transition in human intrahepatic biliary epithelial cells and had a significant reversal effect on epithelial-mesenchymal transition process markers and potential targets in PBC.Conclusion:SMF may exert its therapeutic effects on PBC by acting on important targets such as STAT3,JAK2,TNF-α,IL-1β,Vimentin,and E-cadherin and the pathways in which they are involved.

Anti-hepatitis B virus active secoiridoids from Swertia kouitchensis

Three new secoiridoids, swertiakoulactone (1) and swertiakosides A and B (2 and 3), were isolated from Swertia kouitchensis. Their structures were elucidated by comprehensive spectroscopic analyses including MS, IR, 1D and 2D NMR data. By the anti-hepatitis B virus (HBV) assay on Hep G 2.2.15 cells line in vitro, compound 1 showed moderate activities inhibiting the HBsAg secretion (IC50 = 1.10 mM, SI = 4.39) and HBV DNA replication (IC50 = 1.16 mM, SI = 4.12).

Isolation and Crystal Structure of Xanthones from Swertia Chirayita

In order to study the relationship between biological and pharmacological activities with their structures, a series of tri- and tetra-oxygenated xanthones including 1-hydroxyl-2,3,4,7- tetramethoxy xanthone 1, 1-hydroxyl-2,3,4,5-tetramethoxyl xanthone 2, 1-hydroxyl-3,5-dimethoxy- xanthone 3, 1,8-dihydroxyl-3,5-dimethoxyl xanthone 4 and 1,5,8-trihydroxyl-3-methoxy xanthone 5 have been isolated from Swertia chirayita. Their structures were established on the basis of spectral and chemical evidences. The crystal structure of 5 was also investigated by single-crystal X-ray diffraction analysis. It crystallizes in the triclinic system, space group P?with a = 7.1540(10), b = 7.520(2), c = 10.671(2) , V = 562.7(2) 3 , α = 86.50(3), β = 80.06(3) , γ = 85.00(3), Z = 2, Dc = 1.618 g/m3, R = 0.0405, wR = 0.1028 and F(000) = 284. The molecular structure of 5 is nearly planar and four substituents are much closer to the plane. Compound 5 contains three intermolecular hydro- gen bonds. A recent study shows that phenolic hydroxyls in xanthones are the main active groups capable of scavenging OH and O2.

Minor secoiridoid aglycones from the low-polarity part of the traditional Chinese herb: Swertia mileensis

Eleven new secoiridoid aglycones involving unusual C9-skeleton:swerimilegenins A-F(1-6);bis-C9-skeleton:swerimilegenin G(7);and C_(10)-skeleton:swerimilegenins H−K(8−11),as well as six known ones,were isolated from the low-polarity part of the traditional Chinese herb medicine Swertia mileensis.Their structures were determined by extensive spectroscopic data and X-ray diffraction.Biogenetically,swerimilegenin A(1)belonged to 10-nor-secoiridoid,and swerimilegenins B-F(2-6)were 1-nor-secoiridoids.Erythrocentaurin(12)and gentiogenal(15)showed moderate anti-HBV activity on HepG 2.2.15 cell line in vitro.

A New Monoterpene Glycoside from Swertia punicea

A new monoterpene glycoside, 2,6-dimethyl-2E,6E-octadienoic acid 1,6'-lactone 8-beta-D-glucopyranoside, was isolated from Swertia punicea, accompanying with six known compounds 1-O-primeverosyl-3,7-dimethoxy-8-hydroxyxanthone, 1-O-primeverosyl-3,7,8-tri-methoxyxan-thone, epi-eustomoside, 1-hydroxy-3,7,8-trimethoxyxanthone, 1,8-dihydroxy-3,7-dimethoxy xanthone and isovitexine. Their structures were elucidated based on spectral evidence.

丽江獐牙菜(Swertia delavayi)化学成分研究

目的:研究民族药丽江獐牙菜(Swertiadelavayi)的化学成分,寻找活性物质。方法:用系统溶剂提取,常规的硅胶柱层析和薄层色谱进行分离纯化,根据化合物的物理、化学性质和波谱特征鉴定其结构。结果:从丽江獐牙菜的脂溶性部分分离得到6个化合物,其中3个分别鉴定为齐墩果酸、1,8-二羟基-3,7-二甲氧基酮和1,7,8-三羟基-3-甲氧基酮,另3个结构正在鉴定中。结论:所有化合物均为首次从该植物中得到。

Two New Xanthone Glycosides from Swertia Tetraptera

Two new xanthone glycosides, tetraswerosides A and B, were isolated from the whole plant of Swertia tertraptera. Their structures were determined as 3-O-beta -D-glucopyranosyl-1-hydroxy-4,7-dimethoxyxanthone and 3-O-[beta -D-xylopyranosyl-(1-->6)-beta -D-glucopyranosyl]-1- hydroxy-4,7-dimethoxyxanthone by spectroscopic methods.

An Efficient Method for Plant Regeneration from Calli of <i>Swertia mussotii</i>, an Endangered Medicinal Herb

Swertia mussotii Franch is an endangered medicinal plant in the Qinghai-Tibet Plateau. Its regeneration from callus culture is very difficult. In this study, an efficient method for plant regeneration was developed from its calli. The calli derived from young stem explants of S. mussotii were cultured at two types of temperature treatments to test their efficiency of shoot regeneration. When the calli were cultured at variable temperature (VT, 20℃ during the day and 10℃ at night) treatment, the adventitious shoots were formed at each combination tested. However, that did not occur when the calli were cultured at constant temperature (CT, 25℃) treatment. The best response (53.7%) of plantlet regeneration was obtained on Murashige and Skoog (MS) medium containing 3 mg·l-1 6-benzylaminopurine with 0.5 mg·l-1 α-naphthaleneacetic acid in the VT treatment. The regenerated plantlets were rooted on half-strength MS medium without growth regulators. They flowered in the following subculture. The results indicate that the treatment of day-night temperature difference is a critical factor to callus differentiation in S. mussotii. This protocol can be used for conservation as well as mass propagation of this medicinal plant.

Utilization of Swertia chirayita Plant Extracts for Management of Diabetes and Associated Disorders: Present Status, Future Prospects and Limitations

Diabetes mellitus is referred as common metabolic abnormalities characterized as hyperglycemia,mainly caused due to insufficient production of insulin at cellular level or/and defects in insulin action.Such an endocrine disorder is responsible for serious health problems and its worldwide prevalence is rapidly increasing.Common management of diabetes by oral administration of drugs without creating any side effects is still considered a challenging task and increasing cost of con-ventional medicine in developing countries is another matter of concern.To address these issues,traditional preparations of herbal plant extracts in the form of medicines already gained immense attention.Swertia chirayita is one among such plants which is known for its hypoglycemic potential.Numerous chemical constituents with promising pharmacological properties have been identified from such plant extracts but still,such compounds have not been well characterized,specifically against human application.Hence,more research efforts are necessitated to understand exact mechanism of such compounds and to develop overall safety of such plant formulations.Present review clearly represents antidiabetic properties of Swertia chirayita extract,strategies to be taken to strengthen its safety application on humans and biotechnological interventions that ensure conservation of such endangered species to promote its future application in modern medicine.

A Novel Monoterpene Glycoside from Swertia mileensis

A novel monoterpene glycoside, mileenside, was isolated from Swertia mileensis by repeated normal and reverse phase silica gel chromatography and its structure was elucidated mainly based on spectral evidence.

A new monosaccharide from Swertia punicea Hemsl

A new compound named 1-hydrate, 3-deoxy-α-D-tagatofuranose was isolated from Swertia punicea Hemsl. The structure of compound was determined by 1D and 2D NMR, HRESIMS techniques.

Antioxidants, anti-proliferative, anti-inflammatory, anti-diabetic and anti-microbial effects of isolated compounds from Swertia corymbosa (Grieb.) Wight ex C.B. Clark – An in vitro approach

The present study,antioxidant,enzyme inhibitory,anti-inflammatory and antimicrobial activity of isolated compounds such as Decussatin(1),Gentiacaulein(2),Swertianin(3),1,8-dihydroxy-2,6-dimethoxy xanthone(methylswertianin)(4)8-hydroxy-1,2,4,6-tetramethoxyxanthone(5)and 1,2-dihydroxy-6-methoxyxanthone-8-O--d-xylopyranosyl(6)were investigated using an in vitro model.Results of antioxidant studies revealed that the compound 6 possessed an efficient 2,2-diphenyl-1-picryl-hydrazyl(DPPH•)(IC5007.19±4.56μmol/mL),2,2-azinobis(3-ethylbenzothiozoline-6-sulfonic acid)(ABTS•^+)(42.62±0.25 mmol/L TE/g),superoxide(57.89±3.45μmol/mL),nitric oxide(18.45±1.23μmol/mL)and hydroxyl(12.13±2.76μmol/mL)radical scavenging activities,ferric reducing antioxidant power(14.76±0.10 molar Fe(II)/g),metal chelating(213.85±27.18 mg EDTA/g)ability.Compounds 6 and 3 exhibited significant anti-proliferative activity.Compound 6 displayed strongest antibacterial activity against Streptococcus pneumoniae and Escherichia coli with MIC value of 3.90μg/mL and 21.21±0.25 and 20.27±0.11 mm zone of inhibition at 25μg/mL concentration respectively.In the membrane stabilization and protein denaturation test 3 was the most potent with an IC50 value of 12.57,18.75μmol/mL respectively.

Determination of Ursolic Acid a Biomarker in Different Swertia Species through High Performance Thin Layer Chromatography

A simple highly precise method has been established for the determination of ursolic acid in three species of Swertia viz. S. angustifolia, S. paniculata, and S. alata. The assay combines identification and quantification of the analyte on silica gel 60GF254 HPTLC plates with visualization under UV light and scanning at 510 nm.

藏茵陈有效成分改善代谢综合征的作用机制研究进展

代谢综合征(MS)是以肥胖、糖脂代谢异常以及高血压为主要特征的临床症候群。藏茵陈是我国藏族民间常用药,其功效与MS病机吻合,对MS具有对症治疗潜力。本文对藏茵陈有效成分改善MS的作用机制进行总结发现,龙胆苦苷、獐牙菜苷、獐牙菜苦苷、芒果苷、齐墩果酸等有效成分可通过调节糖脂代谢、改善肥胖、调节心血管系统、抗慢性炎症、抗氧化应激、抗内质网应激、调节自噬、调节肠道菌群紊乱,发挥改善MS的作用。

A New Secoiridoid Glycoside from Swertia cincta

Objective To study the chemical constituents of Swertia cincta. Methods Preparative liquid chromatography was employed. The structures of the compounds were elucidated by spectroscopic analysis. isolated from S. cincta and identified as Results Three secoiridoid glycosides were 8-methoxyl-eustomorusside （1）, secoiridoids eustomorusside （2）, and eustomoside （3）. Conclusion Compound 1 is a new secoiridoid glycoside. Compounds 2 and 3 are isolated from this plant for the first time.

Predictive distribution modeling of Swertia bimaculata in Darjeeling-Sikkim Eastern Himalaya using MaxEnt: current and future scenarios

Background:As global temperatures continue to rise,species distribution modeling is a suitable tool for identifying rare and endangered species most at risk of extinction,along with tracking shifting geographical range.Methods:The present study investigates the potential distribution of Swertia bimaculata in the Darjeeling-Sikkim region of Eastern Himalaya in current and future climate scenarios of GFDL-CM3(Geophysical Fluid Dynamics Laboratory-Climate Model 3)for the year 2050 and year 2070 through MaxEnt presence data modeling.Two sets of variables were used for modeling current scenario.The models were evaluated using AUC(area under the curve)values and TSS(true skill statistic).Results:Habitat assessment of the species shows low and sporadic distribution within the study area.A significant decrease is observed in the possible range of the species in the future climate scenario with the habitat decreasing from 869.48 to 0 km^(2).Resultant maps from the modeling process show significant upward shifting of the species range along the altitudinal gradient.Still,results should be taken with caution given the low number of occurrences used in the modeling.Conclusions:The results thus highlight the vulnerability of the species towards extinction in the near future.

A New Compound from Swertia cincta

Objective To study the chemical constituents from the whole plant of Swertia cincta.Methods The chemical constituents were purified by chromatographic methods such as silica gel column and Sephadex LH-20. The structures of these compounds were elucidated by MS, IR, and NMR analyses. Results Two compounds were isolated from S. cincta. Conclusion Compound 1 is a new compound named swercinctlactone A. Compound 2 is identified as（±）-gentiolactone and its configuration is confirmed by single crystal X-ray diffraction and optical specific rotation.

基于质量源于设计理念的小儿腹痛草标准汤剂的制备工艺及质量标准

目的运用质量源于设计理念(QbD),优化小儿腹痛草标准汤剂的制备工艺,并建立其质量标准。方法根据中药质量标志物理论预测分析关键质量属性;采用失效模型与影响分析筛选关键工艺参数(CPPs);建立关键质量属性的测定方法;根据单因素实验确定初步范围后使用Box-Behnken实验优化提取工艺;以熵值法进行综合评分;建立设计空间,选取较优操作空间进行工艺验证;以最佳工艺制备15批不同产地小儿腹痛草饮片的标准汤剂,最终建立其出膏率、浸出物、薄层色谱、指纹图谱、含量及含量转移率的质量标准。结果以獐牙菜苦苷含量、龙胆苦苷含量及出膏率为关键质量属性;以浸泡时间、加水量、煎煮时间为关键工艺参数;所建立的模型差异有统计学意义;筛选的最佳工艺为:浸泡时间90 min、加水量15倍、煎煮时间30 min(第二煎20 min);出膏率21.13%~30.73%;浸出物含量在82.00%~88.00%;薄层色谱中獐牙菜苦苷斑点清晰;15批样品与参照图谱的相似度均>0.85;獐牙菜苦苷含量250.64~385.21 mg·g^(-1),转移率43.76%~77.73%;龙胆苦苷含量0.69~2.70 mg·g^(-1),转移率56.02%~105.29%。结论基于以上方法及技术筛选出小儿腹痛草标准汤剂制备工艺,可为其配方颗粒的制剂开发及质量控制提供参考。

青海省獐牙菜属植物适宜区预测及主导环境因子分析

目的:了解不同气候变化条件下青海省獐牙菜属植物的潜在地理分布特点,掌握影响其分布的主导气候因子。方法:通过ArcGIS和MaxEnt模型,利用121个獐牙菜属植物地理位点以及19个气候变量,模拟分析影响獐牙菜属植物分布的主要气候因子,预测2050s、2070s的RCP 2.6、RCP 8.5两种气候情景下獐牙菜属植物的分布格局。结果:训练集与测试集AUC值均为0.899,模型推算当前潜在分布区的可信度良好。獐牙菜属植物主要分布在青海省的东部及东南部地区,包括海东、玉树等地。与当前气候相比,獐牙菜属植物在青海省的分布面积在未来不同气候情景下均有所增加,且分布区域逐渐向西偏移。影响青海省獐牙菜属植物分布的主要气候变量从大到小依次为年降水量、最冷季度平均温度、降水量季节性变化、等温性、最干季度降水量、最冷月份最低温度、最暖季度降水量。结论:獐牙菜属植物具有扩大地理分布范围的潜力,降水量和平均温度是限制獐牙菜属植物分布的关键因素,该结果可以为獐牙菜属植物的资源保护及引种驯化措施的制定提供理论依据。

青叶胆总黄酮提取及含量测定

目的探讨青叶胆中黄酮类成分的提取及含量的测定。方法采用芦丁为标准品,NaNO2-Al(NO3)3-NaOH显色法,分光光度法测定青叶胆总黄酮的含量,以提取时间、乙醇浓度、料液比为考察因素,提取率为考察指标,采用正交试验优化提取工艺。结果最佳的提取工艺为70%乙醇、料液比15 mL·g^(-1)、提取60 min,青叶胆总黄酮平均含量为4.65%。结论该工艺简单、操作容易、稳定性好,可作为青叶胆中青叶胆总黄酮的提取工艺。