Arglabin: A mediator of inflammasome modulated and independent myocardial injury (PARA-AMI study).

BACKGROUND: Arglabin is a plant alkaloid (sesquiterpene lactone) that is used as an anticancer drug. It has potential anti-diabetic and anti-atherogenic effects. PURPOSE: Arglabin has drawn particular attention because of its therapeutic effects as an anti-inflammatory agent in multiple diseases. Since arglabin inhibits Epidermal Growth Factor Receptor (EGFR) tyrosine kinase, concerns for cardiotoxic effects are valid. The present study was designed to investigate the protective effects of arglabin on the myocardium. STUDY DESIGN: This study was designed to evaluate the effect of arglabin on the myocardium in an experimental model of myocardial necrosis in rats. Different doses of arglabin (2.5, 5, and 10 µg/kg) were investigated as pre-treatment for 21 days in the isoproterenol (ISO) model of myocardial necrosis groups and per se groups. METHODS: On the 22nd day, hemodynamic, histopathological, electron microscopy, oxidative stress markers, inflammatory mediators, apoptotic markers, inflammasome mediators, and Western blot analysis were performed to evaluate the effects of arglabin. RESULTS: Arglabin pre-treatment showed improvement in hemodynamic parameters and histopathological findings at low doses in isoproterenol-induced myocardial necrosis model of rats. Arglabin administration altered myocardial structure and modulated myocardial function via activation of NFκB/MAPK pathway that led to myocardial injury with an increase in dose. CONCLUSION: Arglabin imparted partial cardio-protection via an inflammasome-dependent pathway and mediated injury through the inflammasome-independent pathway.

The Flow Rate of the Condenser Cooling Water in the Distillation Process Increases the Quality and Quantity of Patchouli Oil.

Indonesia is an important essential oil-exporting country globally, where 40 types of essential oils have been traded on the international market and are products of Indonesia. However, the quality and quantity of patchouli oil produced in Indonesia are still low. Most essential oil processing units use simple or traditional technology and generally have limited production capacity. This study aimed to obtain the optimum water flow rate in a condenser system for patchouli oil production in Maluku, Indonesia. Patchouli oil extraction from fresh patchouli leaves and twigs was carried out by increasing the condenser water discharge rate. Patchouli oil extraction with a condenser cooling water discharge treatment of 1.74 L/min and drying time for 5 days produced the highest patchouli oil yield of 1.4%. The greater the condenser water discharge rate, the better the yield and accumulation of patchouli oil recovery obtained. In addition, based on the results of the analysis of the composition of patchouli oil compounds with GCMS, it can be seen that 13 compounds can be detected in patchouli oil. The three main components of patchouli oil in all condenser cooling water treatments were alpha-guaiene, delta-guaiene, and patchouli alcohol. Considering the results of all parameters mentioned above, the treatment of the condenser cooling water discharge of 1.74 L/min and drying time for 5 days increases the quality and quantity of patchouli oil.

Guaianolide sesquiterpenes and their activity from Artemisia mongolica.

Seven undescribed sesquiterpenes, including three dimeric guaianolide sesquiterpenes artemongolides G-I (1-3) and four sesquiterpene lactones artemanomalide D-G (16-19), along with seventeen known compounds isoabsinthin (4), absinthin (5), 11-eptabsinthin (6), 11, 11'-bis-epiabsinthin (7), 10', 11'- epiabsinthin (8), anabsinthin (9), isoanabsinthin (10), absinthin D (11), anabsin (12), caruifolin D (13), gnapholide (14), caruifolin C (15), 1ß(R),10ß(S)-dihydroxy-3-oxo-11ß (S)H-4,11(13)-guaien-6α(S),12-olide (20), 1α,6α,8α-trihydroxy-5α,7ßH-guaia-3,10(14),11(13)-trien-12-oic acid (21), 1α,6α,8α-trihydroxy-5α,7ßH-guaia-3,9,11(13)-trien-12-oic acid (22), argyinolide J (23), artabsinolide A (24) were isolated from the plant Artemisia mongolica. The structures were determined by interpreting NMR, HRESIMS and ECD data. The X-ray crystal structure of 4, 7 and 8 were reported for the first time. In the anti-vitiligo activity test, compounds 2, 7, 12, 23 and 24 demonstrated activity in promoting melanogenesis at a concentration of 50 µM in B16 cells, with 8-methoxypsoralan (8-MOP) as a positive control. Further research on the mechanism revealed that artemongolides H (2) enhance the expression of MITF and TRPs by upregulating p-Akt and p-GSK-3ß, leading to an increase in ß-catenin content in the cell cytoplasm. Subsequently, ß-catenin translocates into the nucleus, resulting in melanogenesis. The results supported the regulation of melanogenesis by artemongolide H (2) through the Akt/GSK3ß/ß-catenin signaling pathway. The anti-inflammatory results demonstrated that compounds 4, 5, 6, 9 and 14 can inhibit the upregulation of IL-6 mRNA and CCL2 mRNA expression. Compound 12 specifically inhibited the upregulation of IL-6 mRNA expression. These compounds exhibited significant anti-inflammatory activities. The activity results revealed that these sesquiterpene compounds have the potential to become lead compounds for the treatment of vitiligo and inflammatory diseases.

Antiproliferative Activities of Cynaropicrin and Related Compounds against Cancer Stem Cells.

Glioblastoma (GBM) has a high mortality rate despite the availability of various cancer treatment options. Although cancer stem cells (CSCs) have been associated with poor prognosis and metastasis, and play an important role in the resistance to existing anticancer drugs and radiation; no CSC-targeting drugs are currently approved in clinical practice. Therefore, the development of antiproliferative agents against CSCs is urgently required. In this study, we evaluated the antiproliferative activities of 21 sesquiterpenoids against human GBM U-251 MG CSCs and U-251 MG non-CSCs. Particularly, the guaianolide sesquiterpene lactone cynaropicrin (1) showed strong antiproliferative activity against U-251 MG CSCs (IC50 = 20.4 µM) and U-251 MG non-CSCs (IC50 = 10.9 µM). Accordingly, we synthesized six derivatives of 1 and investigated their structure-activity relationships. Most of the guaianolide sesquiterpene lactones with the α-methylene-γ-butyrolactone moiety showed antiproliferative activities against U-251 MG cells. We conclude that the 5,7,5-ring and the α-methylene-γ-butyrolactone moiety are both important for antiproliferative activities against U-251 MG cells. The results of this study suggest that the α,ß-unsaturated carbonyl moiety, which has recently become a research hotspot in drug discovery, is the active center of 1. Therefore, we consider 1 as a potential lead for developing novel drugs targeting CSCs.

Glaucatotones A-I: Guaiane-type sesquiterpenoids from the roots of Lindera glauca with anti-inflammatory activity.

Glaucatotones A - I, nine new guaiane-type sesquiterpenoids, along with two reported compounds, namely (1ß,5ß)-1-hydroxyguaia-4(15),11(13)-dieno-12,5-lactone (10) and pseudoguaianelactone C (11), were isolated from the roots of Lindera glauca. The structures and absolute configurations of these compounds were elucidated by extensive spectroscopic analyses, single-crystal X-ray diffraction, and comparison of experimental and calculated electronic circular dichroism (ECD) data. Structurally, glaucatotone A (1) is characterized as a dihomosesquiterpenoid with an unprecedented 5/5/7/6 ring system. A pair of enantiomers, (±)-glaucatotone B (2a/2b), represent the first rearranged norsesquiterpenoid with a (cyclopentylmethyl)cyclohexane skeleton. 3 is defined as a dinorsesquiterpenoid possessing a 5/7/5 ring system. 4-6 are three guaiane-type norsesquiterpenoids. In vitro bioactivity, 2a selectively inhibited Bcap-37 with IC50 value of 5.60 µM, and 9 selectively inhibited Du-145 with IC50 value of 5.52 µM. The anti-inflammatory activity of 1-9 were tested, and of these compounds, 1, 2a, 2b and 7 exhibited potent inhibitory effects.

DoAP2/ERF89 activated the terpene synthase gene DoPAES in Dendrobium officinale and participated in the synthesis of ß-patchoulene.

Dendrobium officinale Kimura et Migo is a tonic plant that has both ornamental and medicinal properties. Terpenoids are significant and diverse secondary metabolites in plants, and are one of the important natural active ingredients in D. officinale. The AP2/ERF gene family plays a major role in primary and secondary metabolism. However, the AP2/ERF transcription factor family has not been identified in D. officinale, and it is unclear if it is involved in the regulation of terpenoid biosynthesis. This study identified a sesquiterpene synthetase-ß-patchoulene synthase (DoPAES) using transcriptome and terpenic metabolic profile analyses. A total of 111 members of the AP2/ERF family were identified through the whole genome of D. officinale. The tissue-specific expression and gene co-expression pattern of the DoAP2/ERF family members were analyzed. The results showed that the expression of DoPAES was highly correlated with the expression of DoAP2/ERF89 and DoAP2/ERF47. The yeast one-hybrid (Y1H) assays and dual-luciferase experiments demonstrated that DoAP2/ERF89 and DoAP2/ERF47 could regulate the expression of DoPAES. The transcriptional regulatory effects were examined using homologous transient expression of DoAP2/ERF89 in protocorms of D. officinale. DoAP2/ERF89 positively regulated the biosynthesis of ß-patchoulene. This study showed that DoAP2/ERF89 can bind to the promoter region of DoPAES to control its expression and further regulate the biosynthesis of ß-patchoulene in D. officinale. These results provide new insights on the regulation of terpenoid biosynthesis.

In silico toxicologic profile and in vivo trypanocidal activity of estafietin, a sesquiterpene lactone isolated from Stevia alpina Griseb.

Chagas disease is an infection caused by the protozoan Trypanosoma cruzi, affecting 6-8 million people worldwide. Only two drugs are available for its treatment, having a limited efficacy and adverse side-effects. Estafietin is a sesquiterpene lactone isolated from Stevia alpina with in vitro activity against T. cruzi and low cytotoxicity against mammalian cells. The aim of this work was to predict the toxicologic profile of estafietin by in silico methods and assess its in vivo activity on a murine model of Chagas disease. Estafietin showed low toxicity according to pkCSM web tool and passed the PAINS filter from PAINS-remover web server. The treatment of infected mice with 1 mg/Kg/day of estafietin for five consecutive days administrated by intraperitoneal route significatively decreased parasitemia levels and reduced inflammatory infiltrates and myocyte damage on muscle tissue. These results suggest that estafietin had effect both on acute and chronic stages of the infection.

Six undescribed guaianolide-type sesquiterpenes from the aerial parts of Daphne penicillata.

Six undescribed guaianolide sesquiterpenes (1-6) were obtained from the aerial parts of Daphne penicillata. Their structures and absolute configuration were elucidated by HRESIMS, NMR analyses, ECD calculations and single-crystal X-ray diffraction analysis. Structurally, all compounds possess the typical 5,7-fused system of 8,12-guaianolides and this guaianolide-type was first reported to be isolated from Daphne penicillata. All compounds (1-6) were evaluated for anti-inflammatory and cytotoxic activity. Among them, compounds 1 and 5 showed moderate inhibitory effects on LPS-induced NO production in BV2 cells and 4 displayed potential inhibition against Hep3B cells with an IC50 value of 7.33 µM.

Heterodimers of Aromadendrane Sesquiterpenoid with Benzoquinone from the Chinese Liverwort Mylia nuda.

Mylnudones A-G (1-7), unprecedented 1,10-seco-aromadendrane-benzoquinone-type heterodimers, and a highly rearranged aromadendrane-type sesquiterpenoid (8), along with four known analogs (9-12), were isolated from the liverwort Mylia nuda. Compounds 1-6 and 7, bearing tricyclo[6.2.1.02,7] undecane and tricyclo[5.3.1.02,6] undecane backbones, likely formed via a Diels-Alder reaction and radical cyclization, respectively. Their structures were determined by spectroscopic analysis, computational calculation, and single-crystal X-ray diffraction analysis. Dimeric compounds displayed cytoprotective effects against glutamic acid-induced neurological deficits.

MCL attenuates atherosclerosis by suppressing macrophage ferroptosis via targeting KEAP1/NRF2 interaction.

BACKGROUND: Micheliolide (MCL), which is the active metabolite of parthenolide, has demonstrated promising clinical application potential. However, the effects and underlying mechanisms of MCL on atherosclerosis are still unclear. METHOD: ApoE-/- mice were fed with high fat diet, with or without MCL oral administration, then the plaque area, lipid deposition and collagen content were determined. In vitro, MCL was used to pretreat macrophages combined by ox-LDL, the levels of ferroptosis related proteins, NRF2 activation, mitochondrial function and oxidative stress were detected. RESULTS: MCL administration significantly attenuated atherosclerotic plaque progress, which characteristics with decreased plaque area, less lipid deposition and increased collagen. Compared with HD group, the level of GPX4 and xCT in atherosclerotic root macrophages were increased in MCL group obviously. In vitro experiment demonstrated that MCL increased GPX4 and xCT level, improved mitochondrial function, attenuated oxidative stress and inhibited lipid peroxidation to suppress macrophage ferroptosis induced with ox-LDL. Moreover, MCL inhibited KEAP1/NRF2 complex formation and enhanced NRF2 nucleus translocation, while the protective effect of MCL on macrophage ferroptosis was abolished by NRF2 inhibition. Additionally, molecular docking suggests that MCL may bind to the Arg483 site of KEAP1, which also contributes to KEAP1/NRF2 binding. Furthermore, Transfection Arg483 (KEAP1-R483S) mutant plasmid can abrogate the anti-ferroptosis and anti-oxidative effects of MC in macrophages. KEAP1-R483S mutation also limited the protective effect of MCL on atherosclerosis progress and macrophage ferroptosis in ApoE-/- mice. CONCLUSION: MCL suppressed atherosclerosis by inhibiting macrophage ferroptosis via activating NRF2 pathway, the related mechanism is through binding to the Arg483 site of KEAP1 competitively.

Highly oxygenated guaiane-type sesquiterpene lactones from Artemisia sacrorum and their antihepatoma activity.

The ethanol and EtOAc extracts of Artemisia sacrorum exhibited inhibitory effect against HepG2, Huh7, and SK-Hep-1 cell lines with inhibitory ratios of 65.5%, 28.1%, 84.6%, and 93.5%, 82.0%, 89.0% at 200 µg/mL. Twenty-three undescribed guaiane-type sesquiterpene lactones, artemisacrolides A‒W, were isolated from A. sacrorum under the guidance of antihepatoma activity. Their structures were elucidated by spectral data (HRESIMS, IR, UV, 1D and 2D NMR), ECD calculations, and a single-crystal X-ray diffraction. Artemisacrolides A‒U were guaiane-type sesquiterpene lactones possessing α-methylene-γ-lactone and containing acetoxyl groups at C-8, and artemisacrolides V and W represented the first report from the genus Artemisia with a 1,10-rearranged guaiane-type sesquiterpene lactone. Antihepatoma assay suggested that artemisacrolides A‒U demonstrated better inhibitory activity in Huh7 and SK-Hep-1 cells than those of HepG2 cells. Among them, nine compounds exhibited significant inhibitory activity against Huh7 cells with IC50 values of 8.2-14.3 µM, superior or equal to that of sorafenib; seven compounds demonstrated obvious activity against SK-Hep-1 cells with IC50 values of 13.5-19.2 µM, which were equivalent to that of sorafenib. Artemisacrolides B and E were the most active ones in three human hepatoma cell lines with IC50 values of 21.9, 8.2, 16.9 and 22.6, 9.0, 17.3 µM.

[Research progress on natural guaiane-type sesquiterpenoids and their biological activities].

Guaiane-type sesquiterpenoids are a class of terpenoids with [5,7] ring-fused system as the basic skeletal structure composed of three isoprene units, which are substituted by 4,10-dimethyl-7-isopropyl. According to the difference in functional groups and degree of polymerization, they can be divided into simple guaiane-type sesquiterpenoids, sesquiterpene lactones, sesquiterpene dimers, and sesquiterpene trimers. Natural guaiane-type sesquiterpenoids are widely distributed in plants, fungi, and marine organisms, especially in families such as Compositae, Zingiberaceae, Thymelaeaceae, Lamiaceae, and Alismataceae. Guaiane-type sesquiterpenoids have good antibacterial, anti-inflammatory, anticancer, and neuroprotective effects. In this paper, the novel guaiane-type sesquiterpenoids isolated and identified in recent 10 years(2013-2022) and their biological activities were reviewed in order to provide refe-rences for the research and development of guaiane-type sesquiterpenoids.

[A new allo-aromadendrane sesquiterpene from Dendrobium nobile].

To study the chemical constituents in the non-alkaloid part of stems of Dendrobium nobile. The macroporous adsorption resin, MCI, silica gel, RP-C_(18), and Sephadex LH-20 gel, preparative thin layer chromatography, and preparative high-performance liquid chromatography(HPLC) were used to isolate and purify the compounds. The structures of the compound were determined according to the spectra data, physicochemical properties, and relevant references. A total of 8 compounds were isolated from D. nobile, which were soltorvum F(1), p-hydroxyphenylpropionic acid(2), vanillic acid(3), p-hydroxybenzoic acid(4), N-trans-cinnamic acid acyl-p-hydroxybenzene ethylamine(5),(+)-(1R,2S,3R,4S,5R,6S,9R)-2,11,12-trihydroxypicrotoxane-3(15)-lactone(6), dendronobilin H(7), soltorvum E(8). Compound 1 was a novel compound, named as soltorvum F. Compound 8 was isolated from Dendrobium species for the first time.

Micheliolide prevents estrogen deficiency-induced bone loss via inhibiting osteoclast bone resorption.

Osteoporosis is one of the major health problems characterized by decreased bone density and increased risk of fractures. Nowadays, the treating strategies against osteoporosis are efficient, but still have some drawbacks. Micheliolide, a guaianolide sesquiterpene lactone isolated from Michelia compressa and Michelia champac, has been reported to have anti-inflammatory effects. Here, our data suggest that Micheliolide could protect mice from ovariectomy induced bone loss. According to the Micro-CT scan and histomorphometry quantification data, Micheliolide treatment inhibits excessive osteoclast bone resorption without affecting bone formation in estrogen deficiency mice. Consistently, our data suggest that Micheliolide could inhibit osteoclastogenesis in vitro. Additionally, we confirmed that Micheliolide inhibits osteoclasts formation via inhibiting P38 MAPK signaling pathway, and P79350 (a P38 agonist) could rescue this effect. In summary, our data suggest that Micheliolide could ameliorate estrogen deficiency-induced bone loss via attenuating osteoclastogenesis. Hence, Micheliolide could be used as a novel anti-resorptive agent against osteoporosis.

Artemongolins A-K, undescribed germacrane-guaiane sesquiterpenoid dimers from Artemisia mongolica and their antihepatoma activities.

Artemongolins A-K (1-11), which are undescribed sesquiterpenoid dimers, were obtained from Artemisia mongolica and characterized through comprehensive spectral data, including HRESIMS, IR, 1D and 2D NMR, and ECD calculations. The absolute configurations of compounds 1, 4, and 7 were undoubtedly determined by a single-crystal X-ray crystallography. Artemongolins A-K (1-11) featured a rare 5/7/5/5/5/10 hexacyclic system composed of a germacrene and a guaianolide by a fused 2-oxaspiro[4,4]nonane-1-one ring system. Antihepatoma evaluation against three human hepatoma cell lines demonstrated that the most active compounds 5 and 6 displayed inhibitory activity with IC50 values of 88.6 and 57.0 (HepG2), 59.1 and 26.4 (Huh7), and 67.5 and 32.5 (SK-Hep-1) µM, respectively.

An Enantiospecific Synthesis of 5-epi-α-Bulnesene.

As a result of its unique fragrance and wider role in traditional medicine, agarwood produced in Aquilaria spp. and certain other trees has been harvested to near extinction as a natural phenomenon. Artificially induced agarwood production in Aquilaria plantations has sated some of the demand although the product quality is variable. Synthetic chemistry may have a role to play in providing sustainable routes to many of the fragrant components identified in agarwood and its smoke when burnt as incense. In this work, we report efforts towards a total synthesis of the guaiane sesquiterpene α-bulnesene, which is found, along with its more fragrant oxidised derivatives, in agarwood. Following the ring-expansion of (R)-carvone using reported procedures, α-butenylation gave a substrate for samarium diiodide mediated reductive cyclisation, the two butenyl epimers of the substrate each leading to a single bicyclic alcohol (24 and 25). Overall homoconjugate hydride reduction of one of these alcohols was achieved by Lewis acid-mediated ionisation and then hydride transfer from triethylsilane to complete an overall seven-step synthesis of 5-epi-α-bulnesene. This new synthesis paves the way for short routes to both α-bulnesene enantiomers and a study of their aerial and enzymatic oxidation products.

Ten undescribed eremophilane and guaiane sesquiterpenes from Penicillium roqueforti.

Nine undescribed eremophilane sesquiterpenes, one undescribed guaiane sesquiterpene, along with ten known analogues were isolated and identified from fungus Penicillium roqueforti, which was separated from the root soil of Hypericum beanii N. Robson collected from the Shennongjia Forestry District, Hubei Province. Their structures were elucidated on the basis of various spectroscopic analyses, mainly including NMR and HRESIMS data, 13C NMR calculations with DP4+ probability analyses, ECD calculations, and single-crystal X-ray diffraction experiments. Furthermore, all twenty compounds were evaluated for the in vitro cytotoxic activities against seven human tumor cell lines, and the result suggested that 14-hydroxymethylene-1(10)-ene-epi-guaidiol A exhibited considerable cytotoxic activity against the Farage (IC50 < 10 µM, 48 h), SU-DHL-2, and HL-60 cells. Further mechanism study demonstrated that 14-hydroxymethylene-1(10)-ene-epi-guaidiol A could significantly promote apoptosis by inhibiting tumor cell respiration and decreasing intracellular ROS levels, thereby inducing S-phase blockade in tumor cells.

An extensive pharmacological evaluation of novel anti-nociceptive and IL-6 targeted anti-inflammatory guaiane-type sesquiterpenoids from Cinnamomum migao H. W. Li through in-depth in-vitro, ADMET, and molecular docking studies.

Guaiane-type sesquiterpenoids are most prevalent in the genus Cinnamomum. Hence this study investigates the structures, anti-nociceptive and IL-6 targeted anti-inflammatory potential of three novels C-14 guaiane-type sesquiterpenoids and two new monoterpenoids, isolated from Cinnamomum migao. The structures were precisely confirmed and characterized through the modern chromatographic and spectroscopic techniques of HRESIMS, 1D NMR, 2D NMR, experimental circular dichroism (ECD), and calculated (ECD). Novel sesquiterpenoids 1 and 2 exhibited significant anti-inflammatory activities against the NO production and pro-inflammatory cytokines. Their IC50 values were determined as 9.52 and 13.42 µΜ against IL-6 mRNA, respectively. Similarly, subcutaneous injection of n-BuT and EA extracts showed a dose-dependent suppression of formalin-induced tonic biting/licking responses during the tonic antinociceptive phase. Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of guaiane-type sesquiterpenoids 1 and 2 displayed that both compounds have a high level of GIT absorption, with a high zone of safety for cardiac and hepatotoxicity and no inhibition of cytochromes. In addition, molecular docking and simulation studies strengthen the anti-inflammatory potential of sesquiterpene 2 which showed a good binding affinity with IL-6 protein. Overall the inclusive results showed that the extracts and newly isolated guaiane-type sesquiterpenoids from C. migao will provide new evidence for the traditional use of this species to treat inflammation and nociception.

Cinnamigones A-C, three highly oxidized guaiane-type sesquiterpenes with neuroprotective activity from Cinnamomum migao.

Cinnamigones A-C, three undescribed highly oxidized guaiane-type sesquiterpenes were isolated from the fruits of Cinnamomum migao. Cinnamigone A (1), structurally artemisinin-like, is a natural 1,2,4-trioxane caged endoperoxide with an unprecedented tetracyclic 6/6/7/5 ring system. Compounds 2-3 are classic guaiane sesquiterpene featuring different epoxy units. Guaiol (4) is considered to be the precursor of 1-3 in the biosynthesis pathway hypothesis. The planar structures and configurations of cinnamigones A-C were elucidated by spectral analysis, HRESIMS, X-ray crystallography and ECD calculations. Evaluation of the neuroprotective activity of 1-3 on N-methyl-ᴅaspartate (NMDA) toxicity was demonstrated that compounds 1-2 exhibited moderate neuroprotective activity against NMDA-induced neurotoxicity.

Guaiane-Type Sesquiterpenes from the Stems of Fissistigma oldhamii.

Two new guaiane-type sesquiterpenes dysodensiols J and L, one new natural product dysodensiol K together with four known biogenetically related guaiane-type sesquiterpenes were isolated from the stems of Fissistigma oldhamii. Their structures were elucidated by detailed analysis of NMR, HR-ESI-MS, IR and Optical rotations data. Compound 1 contains an uncommon five-membered ether ring. The inhibitory effect of all compounds on the proliferation of primary synovial cells was evaluated. Compound 3 showed inhibitory activity with an IC50 value of 6.8 µM. Compounds 5-7 exhibited moderate inhibitory activity with IC50 values of 23.8, 26.6, and 27.1 µM, respectively.