Exercise-induced modulation of miR-149-5p and MMP9 in LPS-triggered diabetic myoblast ER stress: licorice glycoside E as a potential therapeutic target

Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.

Altered Iron-Mediated Metabolic Homeostasis Governs the Efficacy and Toxicity of Tripterygium Glycosides Tablets Against Rheumatoid Arthritis

Rheumatoid arthritis(RA),a globally increasing autoimmune disorder,is associated with increased disability rates due to the disruption of iron metabolism.Tripterygium glycoside tablets(TGTs),a Tripterygium wilfordii Hook.f.(TwHF)-based therapy,exhibit satisfactory clinical efficacy for RA treatment.However,drug-induced liver injury(DILI)remains a critical issue that hinders the clinical application of TGTs,and the molecular mechanisms underlying the efficacy and toxicity of TGTs in RA have not been fully elucidated.To address this problem,we integrated clinical multi-omics data associated with the anti-RA efficacy and DILI of TGTs with the chemical and target profiling of TGTs to perform a systematic network analysis.Subsequently,we identified effective and toxic targets following experimental validation in a collagen-induced arthritis(CIA)mouse model.Significantly different transcriptome–protein–metabolite profiles distinguishing patients with favorable TGTs responses from those with poor outcomes were identified.Intriguingly,the clinical efficacy and DILI of TGTs against RA were associated with metabolic homeostasis between iron and bone and between iron and lipids,respectively.Particularly,the signal transducer and activator of transcription 3(STAT3)–hepcidin(HAMP)/lipocalin 2(LCN2)–tartrate-resis tant acid phosphatase type 5(ACP5)and STAT3–HAMP–acyl-CoA synthetase long-chain family member 4(ACSL4)–lysophosphatidylcholine acyltransferase 3(LPCAT3)axes were identified as key drivers of the efficacy and toxicity of TGTs.TGTs play dual roles in ameliorating CIA-induced pathology and in inducing hepatic dysfunction,disruption of lipid metabolism,and hepatic lipid peroxidation.Notably,TGTs effectively reversed“iron–bone”disruptions in the inflamed joint tissues of CIA mice by inhibiting the STAT3–HAMP/LCN2–ACP5 axis,subsequently leading to“iron–lipid”disturbances in the liver tissues via modulation of the STAT3–HAMP–ACSL4–LPCAT3 axis.Additional bidirectional validation experiments were conducted using MH7A and AML12 cells to confirm the bidirectional regulatory effects of TGTs on key targets.Collectively,our data highlight the association between iron-mediated metabolic homeostasis and the clinical efficacy and toxicity of TGT in RA therapy,offering guidance for the rational clinical use of TwHF-based therapy with dual therapeutic and toxic potential.

Inhibitory Effect of Flavonoid Glycosides from Chlorophytum comosum on Nasopharyngeal Carcinoma 5-8F Cells and Its Mechanism

[Objectives]To study the inhibitory activity of two flavonoid glycosides isolated from Chlorophytum comosum Laxum R.Br on human nasopharyngeal carcinoma(NPC)cell line 5-8F in vitro and its mechanism.[Methods]The flavonoid glycosides were isolated and purified from the ethanol alcoholic extract of the roots of Liliaceae plant Chlorophytum comosum by silica gel column chromatography,macroporous resin column chromatography,Sephadex LH-20,and reverse column chromatography(ODS).The inhibitory activity of flavonoid glycosides on human nasopharyngeal carcinoma cells was analyzed by CCK-8 method,and the potential mechanism was preliminarily analyzed by molecular docking.[Results]Two flavonoid glycosides were identified as isovitexin 2″-0-rhamnoside and 7-2″-di-O-β-glucopyranosylisovitexin.Two flavonoid glycosides showed promising inhibitory effect on human nasopharyngeal carcinoma cell line 5-8F,with IC_(50) values of 24.8 and 27.5μmol/L,respectively.Molecular docking results showed that the potential targets of two flavonoid glycosides include CyclinD1,Bcl-2β-Catenin,ILK,TGF-β,in addition,two glycosides showed higher predicted binding affinity towards CyclinD1,which verifies the cytotoxicity of the two compounds on human nasopharyngeal carcinoma cell line 5-8F in vitro.[Conclusions]Two flavonoid glycosides are the active molecules in Chlorophytum comosum that can inhibit the proliferation of human nasopharyngeal carcinoma cells,and have the potential to be used in the research and development of anti nasopharyngeal carcinoma drugs.

Synthesis of Phenylpropanoid Glycoside Analogs

The regioselective acylation of unprotected phenylethyl glucoside withcinnamoyl chloride leads to 6-OH cin-namoylated glucoside. In this manner, thirteen phenylpropanoidglycoside analogs were designed and prepared. Their structure was confirmed by ~1H NMR and ^(13)CNMR spectra.

Caffeoyl Glycoside对小鼠免疫细胞功能的影响

本实验室从胡黄连根茎分离到1,6-di-O-caffeoyl-β-D-glucopyranoside单体Caffeoyl Glycoside(CG),体外试验测定其对小鼠免疫细胞功能的影响。通过MTT法检测CG对Balb/c小鼠脾淋巴细胞增殖,NK细胞对K562细胞杀伤活性的影响,以及小鼠腹腔巨噬细胞(PMΦ)能量代谢水平;CG对PMΦ吞噬中性红能力的影响。CG在一定剂量范围内单独或者协同非特异性丝裂原(ConA或LPS)作用均能够显著增强小鼠脾淋巴细胞、PMΦ的增殖能力(P<0.05或P<0.01),CG单独作用就能显著提高NK对K562细胞的杀伤活性(P<0.05或P<0.01)。CG在体外对小鼠主要免疫细胞的增值和功能方面具有显著的促进作用(P<0.05或P<0.01)。研究结果显示CG具有特异性与非特异性的免疫增强作用。

Two New Phenylpropanetriol Glycosides in the Fruits of Melia toosendan

Two new phenylpropanetriol glycosides, named as meliadanoside A (3 - methoxy- 5 - hydroxy-9- (1' - O-β-D-glucopyranosyl) - threo - phenylpropanetriol ) and meliadanoside B (4- hydroxy-7, 8- (2', 1' - O- β- D -glucopyranosyl) - phenylpropanetriol), were isolated from the water-soluble extract of the fruits of Meliatoosendan Sieb. et Zucc., along with threo-guaiacylglycerol. Their structures were elucidated by spectroscopic and chendcal analysis.

Novel Stilbene Glycosides from Polygonum multiflorum

Two new stilbene glycosides (1 and 2), together with nine known compounds (3-11), were isolated from the water extract of Polygonum multiflorum Thunb. The structures of the new compounds were elucidated by their chemical properties and spectroscopic analyses, including extensive 2D NMR experiments. Compound 2 showed strong DNA cleavage activity, and compounds 1, 2 and 10 (2, 3, 4′, 5_tetrahydroxy_ trans _stilbene_2_O_β_ D _glucopyranoside) exhibited significant inhibition of lipid peroxidation.

Phenylethanoid Glycosides from Cultivated Cistanche salsa

Introduction The plants of genus Cistanche G. Beck, which belong to Orobanchaceae family, include about twenty species, and there are four species and one variety are distributed in the northwest part of China. The dried fleshy stem of Cistanche genus plant known as ＇Roucongrong＇ in Chinese traditional medicine, has long been used for kidney deficiency, female infertility, morbid leucorrhea, and neurasthenia. Studies on active components and pharmacological activities show that it possesses significant activities in enhancing potency, anti-fatigue, immuno-modulability, etc, and phenylethanoid glycosides are the major active components. Due to excessive exploitation, its natural resources are facing with exhaustion. In order to improve this situation, the plant has been cultivated on a large scale in the northwest part of China. Up to now, the chemical investigations of the cultivated Cistartcbe salsa have not been undertaken. In this paper we report seven phenylethanoid glycosides from the cultivated Cistanche salsa： echinacoside （1）, cistanoside A （2）, acteoside （3）, isoacteoside （4）, 2＇-acetylacteoside （5）, tubuloside B （6）, and eutigoside A （7）. Among them, compound 7 isolated fronl family Orobanchaceae was reported previously, and compounds 1, 2, 3, 4, 5 and 6 from the cultivated Cistanche salsa are reported for the first time.

New Steroidal Glycosides from Ophiopogon japonicus

Two new C 27 steroidal glycosides, named ophiopojaponin A (1) and B (2), together with two known ones, were isolated from the tubers of the famous traditional Chinese herb Ophiopogon japonicus Ker_Gawl. The spectroscopic and chemical evidence revealed their structures to be pennogenin 3_O_[2′_O_acetyl_α_L_rhamnopyranosyl (1→2)]_β_D_xylopyranosyl (1→3)_β_D_glucopyranoside (1), 26_O_β_D_glucopyranosyl_(22ξ, 25R)_3β, 14α, 22ξ, 26_tetrahydroxyfurost_5_ene 3_O_α_L_rhamnopyranosyl (1→2)_β_D_glucopyranoside (2), diosgenin 3_O_[α_L_rhamnopyranosyl (1→2)]_β_D_xylopyrano_syl (1→3)_β_D_glucopyranoside (3) and ruscogenin 1_O_[α_L_rhamnopyranosyl (1→2)]_β_D_xylopyranosyl (1→3)_β_D_fucopyranoside (4).

Three New Phenolic Glycosides from the Fertile Sprouts of Equisetum arvense

Three new phenolic glycosides, named as equisetumoside A (3-methoxy-11,12-dihydroxy-phenylhexane-9- one-4-O-beta -D-glucopyranoside), equisetumoside B (3-methoxy-4,11-dihydroxy-phenylhexane-9-one12-O-beta -D-glucopyranoside) and equisetumoside C ( cis-ferulic acid potassium salt 4-O-beta -D-glucopyranoside) were isolated from the water-soluble extract of fertile sprouts of Equisetum, arvense L. (Equisetaceae), together with uridine, inosine, 2'-deoxyinosine, 2'-deoxycytidine, tryptophan, thymidine, 5-carboxy-2'-deoxyuridine, coniferin, and kaempferol 3-O-beta -D-sophoroside-7-O-beta -D-glucopyranoside. Their structures were elucidated by spectroscopic analysis and chemical transformation.

Caffeoyl Glycoside对脾淋巴细胞生长周期及膜表面标志的影响

用流式细胞术测定了从西藏胡黄连分离的Caffeoyl Glycoside(CG)对小鼠脾淋巴细胞生长周期及其膜表面标志CD4+、CD8+的影响.结果表明:CG通过促进脾淋巴细胞G0/G1期向DNA合成期(S期)转化,从而促进脾淋巴细胞增殖,对脾淋巴细胞膜表面标志的影响,是通过CG上调CD4+、CD8+和CD4+CD8+双阳性细胞亚群,即主要是通过提高Th细胞的数量发挥免疫增强作用.

Caffeoyl Glycoside对小鼠免疫细胞功能的影响

本实验室从胡黄连根茎分离到1,6-di-O-caffeoyl-β-D-glucopyranoside单体Caffeoyl Glycoside(CG),体外试验测定其对小鼠免疫细胞功能的影响。通过MTT法检测CG对Balb/c小鼠脾淋巴细胞增殖,NK细胞对K562细胞杀伤活性的影响,以及小鼠腹腔巨噬细胞(PMΦ)能量代谢水平;CG对PMΦ吞噬中性红能力的影响。CG在一定剂量范围内单独或者协同非特异性丝裂原(Con A或LPS)作用均能够显著增强小鼠脾淋巴细胞、PMΦ的增殖能力(P<0.05或P<0.01),CG单独作用就能显著提高NK对K562细胞的杀伤活性(P<0.05或P<0.01)。CG在体外对小鼠主要免疫细胞的增值和功能方面具有显著的促进作用(P<0.05或P<0.01)。研究结果显示CG具有特异性与非特异性的免疫增强作用。

A novel phenylpropanoid glycosides and a new derivation of phenolic glycoside from Paris Polyphylla var. yunnanensis

A novel phenylpropanoid glycosides 1, named parispolyside E and a novel derivation of phenolic glycoside 2, named parispolyside G, as well as two known flavonoid glycosides were isolated from the rhizome of Paris polyphylla var. yunnanensis. Their structures were elucidaed by spectroscopic methods.

Two new phenylethanoid glycosides and a new secoiridoid glycoside from the roots of Picrorhiza scrophulariiflora

Two new phenylethanoid glycosides,named scroside H（1）,scroside I（2）,and a new secoiridoid glycoside,named picrogentioside I（3）,have been isolated from the underground parts of Picrorhiza scrophulariiflora.Their structures were elucidated on the basis of spectroscopic evidence.

Steroidal and pregnane glycosides from Ypsilandra thibetica

The whole plants of Ypsilandra thibetica have been analyzed as part of a systematic study on saponin constituents of medicinal plants.This has resulted in the isolation of two new bisdesmosidic furostanol saponins,named ypsilandroside P(1)and ypsilandroside Q(2),and one new pregnane glycoside,named ypsilandroside R(3),together with nine known steroidal glycosides.Their structures were elucidated on the basis of extensive spectroscopic analysis,including that of 2D NMR data,and the results of acidic hydrolysis.Ypsilandroside P(1)was cytotoxicity against two human tumor cell lines.

Itoside O,a new linear monoterpene glycoside from the bark and twigs of Itoa orientalis

To investigate the chemical components of the barks and twigs ofltoa orientalis. A new linear monoterpene glycoside named itoside O was isolated from the crude extract of Itoa orientalis together with 11 known compounds. The new compound was identified to be 3,7-dimethyl-1, 6-octadien-3, 10-dihydroxyl-10-O-α-L-arabinopyranosyl （1 -→6）-O-β-D-glucopyranoside by 1D and 2D NMR analysis, and all known compounds were isolated from this plant for the first time.

STUDIES ON GLYCOSIDES ⅤⅢ.TOTAL SYNTHESIS OF NEW ALKALOID GLYCOSIDES FROM SELAGINELLA DOEDERIENII

Two new alkaloids,hordenine-O- -L-rhamnopyranoside(Ⅰ)and hordenine -0-(6′-trans-cinnamoyl)-4′-O-β-D-glucopyranosyl- -L-rhamnopyranoside(Ⅲ) isolated from Selaginella doederleinii have been synthesized the first time. A new method,in which trifluoroacetoxyl group was used both as a good leaving group and a protecting group for synthesis of O-glycosides with high stereo- selectivity was reported.

Efficacy of cattle encephalon glycoside and ignotin in patients with acute cerebral infarction: a randomized, double-blind, parallel-group, placebo-controlled study

Cattle encephalon glycoside and ignotin(CEGI)injection is a compound preparation formed by a combination of muscle extract from hea lthy rabbits and brain gangliosides from cattle,and it is generally used as a neuroprotectant in the treatment of central and peripheral nerve injuries.However,there is still a need for high-level clinical evidence from large samples to support the use of CEGI.We therefore carried out a prospective,multicenter,randomized,double-blind,parallel-group,placebo-controlled study in which we recruited 319 patients with acute cerebral infarction from 16 centers in China from October 2013 to May 2016.The patients were randomized at a 3:1 ratio into CEGI(n=239;155 male,84 female;61.2±9.2 years old)and placebo(n=80;46 male,34 female;63.2±8.28 years old)groups.All patients were given standard care once daily for 14 days,including a 200 mg aspirin enteric-coated tablet and 20 mg atorvastatin calcium,both taken orally,and intravenous infusion of 250–500 mL 0.9%sodium chloride containing 40 mg sodium tanshinone IIA sulfonate.Based on conventional treatment,patients in the CEGI and placebo groups were given 12 mL CEGI or 12 mL sterile water,respectively,in an intravenous drip of 250 mL 0.9%sodium chloride(2 mL/min)once daily for 14 days.According to baseline National Institutes of Health Stroke Scale scores,patients in the two groups were divided into mild and moderate subgroups.Based on the modified Rankin Scale results,the rate of patients with good outcomes in the CEGI group was higher than that in the placebo group,and the rate of disability in the CEGI group was lower than that in the placebo group on day 90 after treatment.In the CEGI group,neurological deficits were decreased on days 14 and 90 after treatment,as measured by the National Institutes of Health Stroke Scale and the Barthel Index.Subgroup analysis revealed that CEGI led to more significant improvements in moderate stroke patients.No drug-related adverse events occurred in the CEGI or placebo groups.In conclusion,CEGI may be a safe and effective treatment for acute cerebral infarction patients,especially for moderate stroke patients.This study was approved by the Ethical Committee of Peking University Third Hospital,China(approval No.2013-068-2)on May 20,2013,and registered in the Chinese Clinical Trial Registry(registration No.ChiCTR1800017937).

A new triterpene glycoside from sea cucumber Holothuria leucospilota

A new triterpene glycoside, leucospilotaside A, along with a known saponin, isolated from sea cucumber Holothuria leucospilota, and its structure was elucidated as 3β-O-[4-O-sodiumsulfate-β-d-quinovopyranosyl-(1 → 2)-β-d-xylopyranosyl]-holosta-22-ketone-9-en-17α,25α-diol (1) by extensive spectroscopic analysis and chemical methods. Leucospilotaside A (1) has a ketone carbonyl group (22) in the aglycon side chain.

Isolation and Identification of an Acidophilic Fungus and Analysis on the Secreted Glycoside Hydrolases

[Objective] This study aimed to isolate an acidophilic fungus and analyze the acidophilic enzymes secreted by this fungus. [Method] A heterotrophic fungus was isolated from the leaching solution of a uranium ore in Jiangxi Province using oligotrophic acid selective medium （pH 2.5）, and was named RBS-6. This strain was then identified according to its colony morphology and molecular indicator rDNA-ITS. Finally, the glycoside hydrolases secreted by RBS-6 were analyzed. [Result] This fungus RBS-6 was acidophilic, and grew best at pH4.0. Its rDNA-ITS sequence shared the highest homology （98%） with that of Phialophora sp. CGMCC 3329 （GU 082377）. So it was identified as a fungus of Phialophora sp., and was temporarily named as Phialophora sp. RBS-6. It can produce six glycoside hydrolases, in cluding α-galactosidase glucosidase, β-glucosidase, β-mannanase and β-glucanase. All the enzymes were acidophilic, for which the optimum reaction pH was 3.0-4.0. Among them, β-glucanase exhibited the highest activity at pH 3.5 and 50 ℃; in addition, it was heat-stable as 58% of the enzyme activity was remained after incubation at 50 ℃ for 60 min. [Conclusion] The isolated fungus which was identified as an acidophilic member of Phialophora sp., was a new strain producing acidophilic enzymes. This study supplied new data for the research on Phialophora fungi.