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.

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.

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.

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.

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.

Minor antifungal aromatic glycosides from the roots of Gentiana rigescens(Gentianaceae)

Two new phenolic glycosides, 2,3-dihydroxybenzoic acid methyl ester 3-O-β-o-glucopyranosyl-（1-6）-β-D-glucopyranoside （1） and 2,5-dihydroxylbenzofuran 5-O-β-D-xylopyranosyl-（1-6）-O-β-D-glucopyranoside （2）, were isolated as the minor chemical constituents from the roots of Gentiana rigescens, along with 15 known compounds. Their structures were elucidated by detailed spectroscopic analysis, including 1D, 2D NMR and chemical method. All of these compounds were isolated for the first time from the title plant. Moreover, compounds 1 and 2 were tested for the antifungal activities on three plant pathogens Peronophythora litchi, Glomerella cingulata, and Glorosprium musarum.

Isolation and purification of phenylethanoid glycosides from plant extract of Plantago asiatica by high performance centrifugal partition chromatography

Two phenylethanoid glycosides （PhGs） were isolated and purified from the aerial parts of Plantago asiatica for the first time by high performance centrifugal partition chromatography （HPCPC） using ethyl acetate-n-butanol-ethanol-water （0.5：0.5：0.1：1, v/v/v/v）. A total of 45.6 mg of compound 1 and 293.8 mg of compound 2 were purified from 1341 mg of the n-butanol extract of P. asiatica. The structures of the two PhGs were tentatively identified as plantamajoside and aeteoside or isoacteoside by eleetrospray ionization multi stage tandem mass spectrometry （ESI-MS^n） in the negative ion mode.

Monoterpene Glycosides from the Roots of Paeonia lactiflora

A new monoterpene glycoside, together with nine known ones, 3-O-methylpaeoniflorin, mudanpioside J, paeoniflorin, benzoylpaeoniflorin, oxypaeoniflorin, benzoyloxypaeoniflorin, oxybenzoylpaeoniflorin, albiflorin and lactiflorin, was isolated from the roots of Paeonia lactiflora Pall.. The structure of the new compound was elucidated as galloylalbiflorin by the spectro- scopic evidence including ESI-MS, 1D- and 2D-NMR spectra.

Two New Steroidal Glycosides from Liriope muscari

Two new steroidal glycosides named Lm-4 （1） and Lm-5 （2） were isolated from the tubers of Liriope muscari. Their structures were elucidated by 1D and 2D NMR, ESI/MALDIMS techniques, and chemical methods.

Two New C-21 Steroidal Glycosides from Cynanchum aurichulatum

Two new C21 steroidal glycosides, cynanauriculoside I and cynanauriculoside II, were isolated from the roots of Cynanchum aurichulatum. Their structures were established using spectroscopic methods including one and two-dimensional NMR.

Two New Phloroglucinol Glycosides from Lysidice rhodostega Hance

Two new phloroglucinol glycosides, lysidiciside A (1) and lysidiciside B (2), were isolated from the roots of Lysidice rhodostega Hance. Their structures were determined as 1-[(3-methylbutyryl)phloroglucinol]-β-D- glucopyranoside (1), 1- [(3-methylbutyryl)phloro- glucinol]-β-D-glucopyranosyl-5-O-β-D-glucopyranoside (2) on the basis of chemical and spectral analysis .

Two new secoiridoid glycosides from the roots of Picrorhiza scrophulariiflora

From the roots ofPicrorhiza scrophulariiflora, two new secoifidoid glycosides, named picrosecosides Ⅰ and Ⅱ （1, 2） have been isolated. Their structures were elucidated on the basis of chemical and spectropic evidences.

The Synthesis of Gracillin and Dioscin: Two Typical Representatives of Spirostanol Glycosides

Two spirostanol saponins (gracillin and dioscin) which have the typical sugar moieties were synthesized facilely by a general approach.

A new macrolide and glycosides from the stem of Sargentodoxa cuneata

A new macrolide glycoside, cuneataside F was isolated from the n-butanol extract of the stem of Sargentodoxa cuneata. The structure was elucidated on the basis of extensive 1D and 2D NMR as well as HRESI-MS spectroscopic analysis.

Two New Xanthone Glycosides from Polygala tenuifolia

Two new xanthone glycosides, polygalaxanthone IV and V were isolated from the roots of Polygala tenuifolia Willd. Their structures were established as 6-O-[a-L-rhamnopyranosyl- (12)-b-D-glucopyranosyl]-1-hydroxy-3, 7-dimethoxyxanthone (polygalaxanthone IV), and 6-O- [a-L-rhamnopyranosyl-(12)-b-D-glucopyranosyl]-1, 3-dihydroxy-7-methoxyxanthone (polyga- laxanthone V), respectively, on the basis of chemical and spectral evidence.

Two new glycosides from the genus of Cassia

Two new glycosides were isolated and characterized by spectral analysis from the seeds of Cassia obtusifolia and the leaves of Cassia angustifolia. The structure was elucidated as 1-hydroxyl-2-acetyl-3,8-dimethoxynaphthalene-6-O-β-D-apiofuranosyl- （1→2）-β-D-glucopyranoside and 2-acetyl-3-methyl-8-methoxyl-1,4-naphthoquinone-6-O-β-D-glucopyranoside.