Nanomedicines targeting activated immune cells and effector cells for rheumatoid arthritis treatment.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and inflammatory cellular infiltration. Functional cells in the RA microenvironment (RAM) are composed of activated immune cells and effector cells. Activated immune cells, including macrophages, neutrophils, and T cells, can induce RA. Effector cells, including synoviocytes, osteoclasts, and chondrocytes, receiving inflammatory stimuli, exacerbate RA. These functional cells, often associated with the upregulation of surface-specific receptor proteins and significant homing effects, can secrete pro-inflammatory factors and interfere with each other, thereby jointly promoting the progression of RA. Recently, some nanomedicines have alleviated RA by targeting and modulating functional cells with ligand modifications, while other nanoparticles whose surfaces are camouflaged by membranes or extracellular vesicles (EVs) of these functional cells target and attack the lesion site for RA treatment. When ligand-modified nanomaterials target specific functional cells to treat RA, the functional cells are subjected to attack, much like the intended targets. When functional cell membranes or EVs are modified onto nanomaterials to deliver drugs for RA treatment, functional cells become the attackers, similar to arrows. This study summarized how diversified functional cells serve as targets or arrows by engineered nanoparticles to treat RA. Moreover, the key challenges in preparing nanomaterials and their stability, long-term efficacy, safety, and future clinical patient compliance have been discussed here.

Anti-RAFLS Triterpenoids and Hepatoprotective Lignans From the Leaves of Tujia Ethnomedicine Kadsura heteroclita (Xuetong).

A pair of 3,4-seco-cycloartane triterpenoid isomers with a rare peroxy bridge, namely, xuetonins A and B (1 and 2), four new lignans xuetonlignans A-D (3-6), a new sesquiterpene xuetonpene (7), and a new natural product xuetonin C (8), along with 43 known compounds, were obtained from the leaves of Tujia ethnomedicine, Kadsura heteroclita. Their structures and configurations were determined with the help of a combination of 1D- and 2D-NMR, HRESIMS spectra, electronic circular dichroism (ECD), and X-ray diffraction data. Compounds 2, 10, 13-15, and 17-19 showed moderate-to-potent activity against rheumatoid arthritis fibroblast-like synoviocytes (RAFLS) with IC50 values of 19.81 ± 0.26, 12.73 ± 0.29, 5.70 ± 0.24, 9.25 ± 0.79, 5.66 ± 0.52, 11.91 ± 0.44, 13.22 ± 0.27, and 15.94 ± 0.36 µM, respectively. Furthermore, compounds 22, 25, and 31 exhibited significant hepatoprotective effects against N-acetyl-p-aminophenol (APAP)-induced toxicity in HepG2 cells at 10 µM, and the cell viability increased by 12.93, 25.23, and 13.91%, respectively, compared with that in the model group (cf. bicyclol, 12.60%).

[Research progress on chemical constituents and pharmacological activities of Potentilla].

There are 200-500 species of Potentilla(Rosaceae) worldwide, among which 90 species are widely distributed in China and have a long history of ethnic medicinal use. According to our statistics, a total of 367 compounds have been isolated and identified from plants of this genus, including terpenoids, flavonoids, phenolic acids, tannins, and phenylpropanoids. The medicinal materials made from these plants mainly have antioxidative, blood sugar-lowering, anti-inflammatory, anti-tumor, cardiovascular system-protecting, neuroprotective, and hepatoprotective activities. This study systematically reviews the research progress on chemical constituents and pharmacological activities of Potentilla plants to provide a basis for further research and clinical application.

Anti-inflammatory and antioxidant activities of chemical constituents from the flower buds of Buddleja officinalis.

Five new glycosides including mimenghuasu A and B (1-2), isolinarin (3), cyclocitralosides A and B (4-5), along with forty-seven known compounds were isolated from the flower buds of Buddleja officinalis. These structures were elucidated by extensive spectroscopic analysis (UV, IR, 1 D, 2 D NMR, and MS spectra). The anti-inflammatory activities of the isolated compounds were determined by enzyme-linked immunosorbent assay (ELISA) on the expression of TNF-α (LPS-activated RAW264.7 cells) and MTT experiment on LPS-induced HUVECs proliferation effects. Good suppressive effects on the expression of TNF-α were shown by 4 and 5 with IC50 values of 19.35 and 22.10 µM, respectively, compared to positive control indomethacin (IC50 16.40 µM). In addition to this, some isolated compounds exhibited excellent antioxidant activities including compounds 16, 18, 29, 39, and 47 (IC50 µM: 82.59, 72.94, 33.65, 46.67, and 20.81, respectively) with almost the same or stronger potency with reference to vitamin C as positive control (IC50 81.83 µM).

A Rapid and Accurate 1HNMR Method for the Identification and Quantification of Major Constituents in Qishen Yiqi Dripping Pills.

BACKGROUND: Qishen Yiqi dripping pills (QSYQ), composed of four herbal medicines-Salvia miltiorrhiza, Astragalus membranaceus, Panax notoginseng, and Dalbergiaodorifera-are widely used to treat ischemic cerebrovascular and hemorrhagic cerebrovascular conditions. OBJECTIVE: In this study, a rapid and accurate proton NMR (1HNMR) spectroscopy method was established to control the quality of QSYQ and ensure their clinical efficacy. METHOD: Firstly, different types of metabolites were identified based on the proton signal peaks of chemical shifts, coupling constants, and related information provided through two-dimensional NMR spectroscopy. Secondly, a quantitative 1HNMR method was established for the simultaneous determination of major constituents in QSYQ samples. In addition, an HPLC method was performed to verify the results obtained by the quantitative proton NMR (qHNMR)  method. RESULTS: In the present study, 26 metabolites were identified in the 1HNMR spectra of QSYQ. In addition, a rapid and accruate qHNMR method was established for the simultaneous determination of protocatechualdehyde, rosmarinic acid, danshensu, calycosin-7-O-ß-D-glucoside, and ononin in ten batches of QSYQ samples for the first time. Moreover, the proposed qHNMR method and HPLC method were compared using Bland-Altman and plots Passing-Bablok regression, indicating no significant differences and a strong correlation between the two analytical methods. CONCLUSIONS: This method is an important tool for the identification and quantification of major constituents in QSYQ. HIGHLIGHTS: Compared with traditional HPLC, the established qHNMR method has the advantages of simple sample preparation, short analysis time, and non-destructive analysis.

Simultaneous Determination of 12 Bioactive Constituents in Bupi Yiqi No. 1 Recipe by Ultrahigh-Performance Liquid Chromatography Tandem Mass Spectrometry.

BACKGROUND: Bupi Yiqi No. 1 Recipe (BPYQ), a traditional Chinese medicine formula, has been widely used as a treatment of multidrug resistance during chemotherapy in colorectal cancer and for the prevention of gastrointestinal cancer recurrence for decades. OBJECTIVE: In this study, a rapid, reliable, and accurate ultrahigh-performance LC (UHPLC) coupled with electrospray ionization (ESI)-tandem MS (MS/MS) method was developed for the simultaneous determination of 12 major bioactive components, including protocatechuic acid, astilbin, rutin, calycosin-7-O-ß-D-glucoside, ginsenoside Re, ononin, isoliquiritigenin, calycosin, apigenin, ginsenoside Rb1, formononetin, and glycyrrhizic acid in BPYQ. METHODS: The chromatographic separation of the analytes was achieved on a Poroshell 120 SB-Aq column (50 × 2.1 mm, 1.7 µm) with a mobile phase of acetonitrile and 0.1% (v/v) formic acid aqueous solution. The flow rate and column temperature were set at 0.4 mL/min and 30°C, respectively. Mass spectrometric detection of the analyses was performed on multiple reaction monitoring mode in positive and negative ESI mode. RESULTS: The established UHPLC-ESI-MS/MS method was validated in terms of the linearity, precision, repeatability, stability, and accuracy. All calibration curves of the 12 compounds showed good linearity, with correlation coefficients (r) greater than 0.9980 within the test ranges. The LODs and LOQs for the 12 compounds were in the ranges of 0.08-1.32 and 0.27-5.28 ng/mL, respectively. The average recoveries of all the standard compounds were between 98.4 and 102.9%, and their relative SD values ranged from 1.24 to 3.78%. CONCLUSIONS: The proposed method can provide a meaningful basis for the QC of BPYQ. HIGHLIGHTS: The established UHPLC-ESI-MS/MS method was demonstrated to be a powerful tool for quantifying the 12 compounds in BPYQ.