Search Results (13)

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized primarily by the synovial infiltration of inflammatory cells. Macrophage infiltration in the joint synovium is one of the early hallmarks of RA disease activity. Cortex periplocae, which has been widely employed in traditional Chinese medicine (TCM) to alleviate RA, harbors a bioactive compound known as Periploca sepium periplosides (PePs). In this study, collagen antibody-induced arthritis (CAIA) was established in mice through the administration of collagen antibodies and lipopolysaccharide (LPS), followed by treatment with PePs. The therapeutic effects of PePs were evaluated by measuring paw thickness, clinical arthritis scores, and histological changes in joint tissues. Flow cytometry and qRT-PCR were used to assess macrophage polarization in vivo and in vitro. The findings indicate that PePs effectively attenuated CAIA by suppressing the polarization of RAW264.7 cells towards the M1 phenotype while promoting their polarization towards the M2 phenotype. These results provide valuable insights into the scientific significance of PePs as a potential therapeutic agent for RA. Full article

Erythroleukemia is a rare form of acute myeloid leukemia (AML). Its molecular pathogenesis remains vague, and this disease has no specific therapeutic treatments. Previously, our group isolated a series of Carbon 21 (C-21) steroidal glycosides with pregnane skeleton from the root of Cynanchum atratum Bunge. Among them, we found that a compound, named BW18, can induce S-phase cell cycle arrest and apoptosis via the mitogen-activated protein kinase (MAPK) pathway in human chronic myeloid leukemia K562 cells. However, its anti-tumor activity against erythroleukemia remains largely unknown. In this study, we aimed to investigate the anti-erythroleukemia activity of BW18 and the underlying molecular mechanisms. Our results demonstrated that BW18 exhibited a good anti-erythroleukemia activity in the human erythroleukemia cell line HEL and an in vivo xenograft mouse model. In addition, BW18 induced cell cycle arrest at the G2/M phase and promoted megakaryocytic and erythroid differentiation in HEL cells. Furthermore, RNA sequencing (RNA-seq) and rescue assay demonstrated that overexpression of platelet-derived growth factor receptor beta (PDGFRB) reversed BW18-induced megakaryocytic differentiation in HEL cells, but not erythroid differentiation. In addition, the network pharmacology analysis, the molecular docking and cellular thermal shift assay (CETSA) revealed that BW18 could inactivate Janus tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, which might mediate BW18-induced erythroid differentiation. Taken together, our findings elucidated a novel role of PDGFRB in regulating erythroleukemia differentiation and highlighted BW18 as an attractive lead compound for erythroleukemia treatment. Full article

‘Globemaster’ is an ornamental hybrid cultivar whose parent plants are Allium cristophii and A. macleanii. The chemical constituents of ‘Globemaster’ bulbs have not yet been examined; thus, a systematic phytochemical investigation was undertaken herein. A series of chromatographic separations of the MeOH extract of ‘Globemaster’ bulbs afforded 27 steroidal glycosides (1–27), which are classified into 23 spirostanol glycosides (1–8 and 11–25), two furostanol glycosides (9 and 26), a pregnane glycoside (10), and a cholestane glycoside (27). The structures of the hitherto undescribed compounds (1–10) were determined from the two-dimensional NMR spectroscopic data and hydrolysis. The cytotoxicity of the isolated compounds (1–27) toward HL-60 human promyelocytic leukemia cells, A549 human adenocarcinoma lung cancer cells, and SBC-3 human small-cell lung cancer cells was evaluated. Compounds 8, 22, 23, 24, and 26 exhibited cytotoxicity toward all cell lines in a dose-dependent manner, with IC₅₀ values in the 1.3–49 µM range. Full article

The ethnobotanical plant Marsdenia tenacissima has been used for hundreds of years for Dai people in Yunnan Province, China. Previously, chemical investigations on this plant have revealed that pregnane glycosides were the main biological constituents. Nine new pregnane glycosides, marsdeosides A–I (1–9), were isolated from cultivated dried stems of the medicinal plant Marsdenia tenacissima in this study. The structures were analyzed by extensive spectroscopic analysis, including 1D, 2D NMR, HRESIMS, and IR spectroscopic analysis. The absolute configurations of the sugar moieties were identified by comparing the R_f values and specific optical rotations with those of the commercially available standard samples and the data reported in the literature. Marsdeosides A (1) featured an unusual 8,14-seco-pregnane skeleton. Compounds 1, 8, and 9 showed activity against nitric oxide production in lipopolysaccharide-activated macrophage RAW264.7, with IC₅₀ values of 37.5, 38.8, and 42.8 μM (L-NMMA was used as a positive control, IC₅₀ 39.3 μM), respectively. This study puts the knowledge of the chemical profile of the botanical plant M. tenacissima one step forward and, thereby, promotes the sustainable utilization of the resources of traditional folk medicinal plants. Full article

Mandevilla Lindl. is an important genus of the Apocynaceae family, not only as ornamental plants but also for its medicinal uses. In Brazil, Mandevilla species are indicated to treat asthma and skin infections, their anti-inflammatory potential and wound healing properties are also reported in the literature. Concerning their chemical composition, this group of plants is a conspicuous producer of pregnane glycosides. Mandevilla dardanoi is an endemic species from the Brazilian semiarid region not studied by any phytochemical methods. In view of the medicinal potential of Mandevilla species, this study aimed to isolate new pregnane glycosides from M. dardanoi. To achieve this main goal, modern chromatography techniques were employed. Five new pregnane glycosides, dardanols A-E, were isolated from the roots of M. dardanoi by HPLC. Their structures were determined using extensive 1D and 2D-NMR and mass spectrometry (MSⁿ and HRESIMS) data. The cytotoxicity and the anti-inflammatory potential of these compounds were evaluated. The first was evaluated by measuring proinflammatory cytokines and nitric oxide production by stimulated macrophages. Dardanols were able to inhibit the production of nitric oxide and reduce IL-1β and TNF-α. The current work demonstrates the chemodiversity of Brazilian semiarid species and contributes to amplifying knowledge about the biological potential of the Mandevilla genus. Full article

For our interest in the potential biologically active and structurally unique steroidal glycosides, continued phytochemical investigation of Cynanchum taihangense was carried out; twelve new seco-pregnane glycosides, cynataihosides I–L (1–4), M-T (7–14), and two known glycosides, glaucoside A (5) and atratcynoside F (6), were isolated from the 95% ethanol extract of Cynanchum taihangense. Two new aglycones were found among compounds 10, 11, 13, and 14. The structures of the glycosides were elucidated based on 1D and 2D NMR spectroscopic data, HR-ESI-MS analysis, and chemical evidence. The cytotoxicity of compounds against three human tumor cell lines (HL-60, THP-1, and PC-3) were evaluated by MTT assay. Compound 11 displayed significant cytotoxicity against THP-1 and PC-3 cell line with IC₅₀ values of 5.08 and 22.75 μm, respectively. Compounds 3 and 14 exhibited moderate and selective cytotoxicity on HL-60 and THP-1 with IC₅₀ values of 17.78 and 16.02 μm, respectively. Full article

From the aerial parts of Euphorbiagossypina var. coccinea Pax., eight new pregnane glycosides (euphogossypins A–H, 1–8) of the cynanforidine and deacetylmetaplexigenin aglycons, two new lignans (gossypilignans A and B, 9 and 10), and four known compounds, namely, the pregnane 12-O-benzoyldeaxcylmetaplexigenin (11), the lignan 9α-hydroxypinoresinol (12), and the flavonoids naringenin (13) and quercitrin (14) were isolated. The structure elucidation of the new compounds was carried out by a spectroscopic analysis, including HRMS, 1D (¹H, ¹³C JMOD), and 2D NMR (HSQC, ¹H–¹H COSY, HMBC, and NOESY) experiments. The obtained pregnane glycosides were substituted with acetyl and benzoyl ester moieties, and sugar chains containing thevetose, cymarose, digitoxose, and glucose monosaccharides. All of the compounds are described for the first time from E. gossypina var. coccinea. The isolated pregnanes and lignans were tested for their antiproliferative activity on HeLa cells using the MTT assay; the compounds exerted no significant effect against the tumor cells. Full article

Methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Acinetobacter baumannii (MDRAB) present a serious challenge because of their capability to cause biofilm resistance to commonly used antibiotics producing chronic infections and hindering the process of wound healing. In the current study, we investigated the antibacterial activity of Caralluma quadrangula extracts (MeOH, and its fractions CH₂Cl₂ and n-butanol) against multidrug-resistant MRSA USA300 and A. baumannii AB5057. In vitro, the MeOH extract and both fractions of C. quadrangula significantly inhibited biofilm formation and disrupted previously established biofilm by MRSA and MDRAB at all the tested concentrations (0.625, 0.313, and 0.156 mg/mL). In vivo, C. quadrangula extracts successfully decreased bacterial loads in MRSA-infected skin lesions in mice. Four pregnane glycosides and one flavone glycoside were isolated from the bioactive n-butanol fraction. The isolated compounds (Rus A–E) were tested for their biofilm inhibition and biofilm detachment activities. The results revealed that Rus C was the most active compound (IC₅₀ = 0.139 mmole), while Rus E was the least active (IC₅₀ = 0.818 mmole). These results support the potential use of C. quadrangula extracts or their isolated compounds for hindering the biofilm attachment and the virulence of MRSA and MDRAB and their application as a topical antimicrobial preparation for MRSA skin infections. Full article

Gymnema sylvestre, a medicinal plant, has been used in Indian ayurvedic traditional medicine for the treatment of diabetes. Phytochemical investigation of Gymnema sylvestre led to the isolation of five new pregnane glycosides, gymsylosides A–E (1–5) and four known oleanane saponins, 3β-O-β-D-glucopyranosyl (1→6)-β-D-glucopyranosyl oleanolic acid 28-O-β-D-glucopyranosyl ester (6), gymnemoside-W1 (7), 3β-O-β-D-xylopyranosyl-(1→6)-β-D- glucopyranosyl-(1→6)-β-D-glucopyranosyl oleanolic acid 28-O-β-D-glucopyranosyl ester (8), and alternoside XIX (9). Their structures were identified based on spectroscopic evidence and comparison with those reported in the literature. All compounds were evaluated for their α-glucosidase and α-amylase inhibitory activities. Compounds 2–4 showed significant α-amylase inhibitory activity, with IC₅₀ values ranging from 113.0 to 176.2 µM. Full article

The genus Periploca belongs to the family Apocynaceae, which is composed of approximately ten species of plants according to incomplete statistics. Most of these plants serve as folk medicines with a long history, especially Periploca sepium and Periploca forrestii. The botanical classifications, chemical constituents, biological activities and toxicities of the genus Periploca were summarized in the literature from 1897 to early 2019. Though the botanical classification of this genus is controversial, these species are well-known to be rich sources of diverse and complex natural products—above all, cardiac steroids and C₂₁ pregnane steroids with special structures and obvious pharmacological activities. The various crude extracts and 314 isolated metabolites from this genus have attracted much attention in intensive biological studies, indicating that they are equipped with cardiotonic, anti-inflammatory, immunosuppressive, antitumor, antimicrobial, antioxidant, insecticidal and other properties. It is noteworthy that some cardiac glycosides showed hepatotoxicity and cardiotoxicity at certain doses. Therefore, in view of the medical and agricultural value of the genus Periploca, in-depth investigations of the pharmacology in vivo, the mechanisms of biological actions, and the pharmacokinetics of the active ingredients should be carried out in the future. Moreover, in order to ensure the safety of clinical medication, the potential toxicities of cardiac glycosides or other compounds should also be paid attention. This systematic review provides an important reference base for applied research on pharmaceuticals and pesticides from this genus. Full article

Cynatratoside A (CyA) is a C₂₁ Steroidal glycoside with pregnane skeleton isolated from the root of Cynanchum atratum Bunge (Asclepiadaceae). This study aimed to investigate the effects of CyA on concanavalin A (Con A)-induced autoimmune hepatitis (AIH) and the underlying mechanism. CyA was orally administered to mice at 10 and 40 mg/kg 8 h before and 1 h after Con A treatment. The effects of CyA on Con A-induced spleen and liver in mice were assessed via histopathological changes, T lymphocyte amounts and the expressions of IL-1β and ICAM-1. Con A-induced L-02 hepatocytes were used to evaluate whether CyA (0.1–10 μM) can directly protect hepatocytes from cytotoxicity and the possible mechanism. The results revealed that CyA treatment could significantly improve the histopathological changes of spleen and liver, reduce the proliferation of splenic T lymphocytes, and decrease the expressions of IL-1β and ICAM-1 in liver. The experiment in vitro showed that CyA inhibited Con A-induced hepatotoxicity in a concentration-dependent manner. CyA (10 μM) significantly increased/decreased the expression of Bcl-2/Bax and reduced the levels of cleaved caspases-9 and -3. Our study demonstrated for the first time that CyA has a significant protective effect on Con A-induced AIH by inhibiting the activation and adhesion of T lymphocytes and blocking hepatocyte apoptosis. Full article

Three new 14,15-secopregnane-type glycosides, stauntosides UA, UA₁, and UA₂, were isolated from the roots of Cynanchum stauntonii. The three compounds share the first reported and same basic structural features of 3β-hydroxy-14:16,15:20,18:20-triepoxy-5α:9α-peroxy-14,15-secopregnane-6,8(14)-diene named as stauntogenin G as the aglycones. The structures of the new compounds were characterized on the basis of extensive spectroscopic analyses, mainly 1D and 2D NMR and MS methods and chemical analysis. The isolation and identification of the new compounds graced the structural diversity of pregnane-type steroids from C. stauntonii. Full article

Four new pregnane glycosides 1–4 were isolated from the ethanol extract of the stem of Gymnema sylvestre and named gymsylvestrosides A–D. Hydrolysis of compound 1 under the catalysis of Aspergilus niger β-glucosidase afforded compound 5 (gymsylvestroside E). Their structures were determined by spectroscopic methods such as HRESIMS, 1D and 2D NMR, as well as HMQC-TOCSY experiment. Compounds 1–4 were screened for Saccharomyces cerevisiae α-glucosidase inhibitory activity. Full article