Immunosuppressive nitrogen-containing triterpenoid saponins from Mussaenda erosa and the therapeutic efficacy of heinsiagenin A in a murine lupus erythematosus model.

Eight novel nitrogen-containing triterpenoid saponins, designated mussaerosides A-H (1-8), and ten known ones (9-18) were obtained from the aerial parts of Mussaenda erosa Champ (Rubiaceae). Structural characterization was achieved through spectroscopic techniques and chemical derivatization. Immunosuppressive screening of the saponins and sapogenin heinsiagenin A revealed potent inhibition of T- and B-lymphocytes proliferation, and the latter exhibited potent inhibitory activities against the proliferation of ConA-induced T lymphocyte (CC = 22.

Structural optimization of phthalazine derivatives for anti-HBV activities to improve oral bioavailability.

The hepatitis B virus (HBV) capsid protein forms a protective nucleocapsid essential for viral replication, establishing capsid assembly modulation as a promising therapeutic strategy. Based on previous mechanistic studies, we identified phthalazine derivatives as potent HBV capsid assembly modulators (CAMs), with Yhhu6517 exhibiting submicromolar antiviral activity in vitro. However, its clinical translation was hindered by poor oral pharmacokinetics (PK), due to rapid first-pass metabolism of oxidation-prone primary alcohol groups.

Discovery of novel Ebola entry inhibitors with 1,2,3,4-tetrahydroisoquinoline-3-carboxamide based on (3S,4aS,8aS)-2-(3-amino-2-hydroxypropyl) decahydroisoquinoline-3-carboxamide scaffold.

Novel Ebola entry inhibitors were designed and synthesized based on decahydroisoquinolines by streamlining non-essential functional groups that do not compromise activity. All novel derivatives were evaluated for their anti-Ebola activities and cytotoxicitiies in a defective Ebola virus model. A novel tetrahydroisoquinoline Ebola virus entry inhibitor, Hu7, was readily available with antiviral activity comparable to previous findings, while demonstrating a marked reduction in toxicity.

Therapeutic potential and pharmacological mechanisms of Traditional Chinese Medicine in gout treatment.

Gout is a systemic metabolic disorder caused by elevated uric acid (UA) levels, affecting over 1% of the population. The most common complication of gout is gouty arthritis (GA), characterized by swelling, pain or tenderness in peripheral joints or bursae, which can lead to the formation of tophi. At present, western medicines like colchicine, febuxostat and allopurinol are the primary treatment strategy to alleviate pain and prevent flare-ups in patients with GA, but they have significant side effects and increased mortality risks.

Periplosides Extract from Improve Collagen Antibody-Induced Arthritis by Regulating Macrophage Polarization.

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. , which has been widely employed in traditional Chinese medicine (TCM) to alleviate RA, harbors a bioactive compound known as periplosides (PePs).

From Hit to Lead: Discovery of First-In-Class Furanone Glycoside D228 Derived from for the Treatment of Inflammatory Bowel Disease.

TNFα and related inflammatory factor antibody drugs have been orchestrated for the treatment of inflammatory bowel disease (IBD). However, antibody drugs elicited inevitable disadvantages and small molecule drugs are in an urgent need. Herein, we described the discovery, design, synthesis, and SAR studies from furanone glycoside compound (hit) isolated from to (lead).

Linear fractal evolution characteristics of rock crack distributions during loading process.

To investigate the fractal characteristics of rock crack distributions during the loading process, discrete element method was used to make rock samples with joints and record the crack propagation. The Box-counting method was used to quantitatively analyze the fractal dimension of the crack distribution at each moment, and the relationship between the crack fractal dimension and strain ratio was established based on fractal theory. The results indicated that the relationship between the fractal dimension of the crack distribution and strain ratio showed a strong linear characteristic.

On the nature of Cu-carbon interaction through N-modification for enhanced ethanol synthesis from syngas and methanol.

Direct conversion of syngas into ethanol is an attractive process because of its short route and high-added value, but remains an enormous challenge due to the low selectivity caused by unclear active sites. Here, the Cu(111) supported N-modified graphene fragments CN/Cu(111) ( = 0-2) are demonstrated to be an efficient catalyst for fabricating ethanol from syngas and methanol. Our results suggest that the Cu-carbon interaction not only facilitates CO activation, but also significantly affects the adsorption stability of C intermediates and finally changes the fundamental reaction mechanism.

Asymmetric analogous hyperbola model of overburden movement and its verification.

The extraction of underground coal resources induces the fracture and movement of overlying strata, leading to geological hazards such as surface deformation, cracks, and even subsidence. Utilizing the analogous hyperbola model of overlying strata movement, we conducted a mechanical analysis to examine the asymmetric fracture mechanism resulting from coal seam mining in thick loose strata. An asymmetric analogous hyperbola model was established by introducing distinct virtual half-axis lengths (b).

Tanreqing injection demonstrates anti-dengue activity through the regulation of the NF-κB-ICAM-1/VCAM-1 axis.

Background: Tanreqing injection (TRQ) has been employed in clinical practice as a treatment for dengue fever (DF). Nevertheless, the precise pharmacological mechanism underlying its efficacy remains elusive.

Method: Network pharmacology, molecular docking, transcriptome sequencing, and experimental evaluation were employed to analyze and study the inhibitory potential of TRQ against dengue virus (DENV).

Modular Biomimetic Strategy Enables Discovery and SAR Exploration of Oxime Macrocycles as Influenza A Virus (H1N1) Inhibitors.

Although vaccination remains the prevalent prophylactic means for controlling Influenza A virus (IAV) infections, novel structural antivirus small-molecule drugs with new mechanisms of action for treating IAV are highly desirable. Herein, we describe a modular biomimetic strategy to expeditiously achieve a new class of macrocycles featuring oxime, which might target the hemagglutinin (HA)-mediated IAV entry into the host cells. SAR analysis revealed that the size and linker of the macrocycles play an important role in improving potency.

N-Containing triterpenoid saponins from Mussaenda densiflora and identification of heinsiagenin A as a potent immunosuppressant.

Eleven triterpenoid saponins, including five new compounds, which were named densiflorasides A - E (1 - 5), were isolated from aerial parts of Mussaenda densiflora (Rubiaceae). Their structures were elucidated based on spectroscopic and single-crystal X-ray diffraction analyses and chemical methods. All the isolated compounds and the aglycone heinsiagenin A were evaluated for their immunosuppressive and antiosteoclastogenic activities in vitro.

Interplay of IL-17A/IL-17RA signaling with microbial homeostasis in systemic anti-tumoral responses.

Enteric IL-17RA deficiency leads to gut dysbiosis, consequently initiating the proliferation of tumors at remote locations. The deficiency or blockade of enteric IL-17RA induces the secretion of IL-17A by B cells and Th17 cells in response to microbial signals, resulting in a systemic elevation of IL-17A and fostering the growth of remote tumors. This figure was created with BioRender.

Macrolide sesquiterpene pyridine alkaloids from Celastrus monospermus and evaluation of their immunosuppressive and anti-osteoclastogenesis activities.

Phytochemical investigation of the stems of Celastrus monospermus Roxb enabled isolation and identification of fifteen new macrolide sesquiterpene pyridine alkaloids (1-15) along with five known analogues. Their structures were elucidated by comprehensive spectroscopic analysis (NMR, HRESIMS, IR, UV), chemical hydrolysis, and single crystal X-ray diffraction analysis. Bioassay of the abundant isolates revealed that seven compounds inhibited the proliferation of B lymphocytes with IC values ranging between 1.

Physical Mechanism of Selective Healing of Nanopores in Condensed Matter under the Influence of Laser Irradiation and Plasma.

The investigation of the features of laser control over the state of nanoscale objects in solid materials is an urgent task of condensed matter physics. We experimentally established the potential for the simultaneous enhancement of hardness and resistance to surface cracking in a titanium alloy due to selective laser irradiation. The regularities of selective heating near nanopores and the influence of the nanopore system on the features of isotherm propagation have been revealed.

Synthesis of 2-amino-9-chromeno[2,3-]thiazol-9-ones with anti-inflammatory activity cascade reactions of 2-amino-3 iodochromones with amines and carbon disulfide.

A simple and efficient synthetic approach to 2-amino-9-chromeno[2,3-]thiazol-9-ones copper-promoted cascade reactions was developed. The reaction employed easily available 2-amino-3-iodochromones and amines as substrates and the targeting tricyclic compounds could be obtained with moderate to good yields. Even more important, several synthesized compounds exhibited potent anti-inflammatory activities, which suggested that this protocol may provide valuable hits for drug development in the future.

Reversible SAHH inhibitor ameliorates MIA-induced osteoarthritis of rats through suppressing MEK/ERK pathway.

Osteoarthritis (OA) is characterized by gradual articular cartilage degradation, accompanied by persistent low-grade joint inflammation, correlating with radiographic and pain-related progression. The latent therapeutic potential of DZ2002, a reversible inhibitor of S-adenosyl-L-homocysteine hydrolase (SAHH), holds promise for OA intervention. This study endeavored to examine the therapeutic efficacy of DZ2002 within the milieu of OA.

Forsythia suspensa (Thunb.) Vahl extract ameliorates ulcerative colitis via inhibiting NLRP3 inflammasome activation through the TLR4/MyD88/NF-κB pathway.

Background: Ulcerative colitis (UC), a chronic inflammatory disease, is caused by abnormal immune system reactions resulting in inflammation and ulcers in the large intestine. Phillygenin (PHI) is a natural compound found in Forsythia suspensa (Thunb.) Vahl, which is known for its antipyretic, anti-inflammatory, antiobesity, and other biological activities.

A novel phthalazinone derivative as a capsid assembly modulator inhibits hepatitis B virus expression.

Development of new anti-hepatitis B virus (HBV) drugs that target viral capsid assembly is a very active research field. We identify a novel phthalazinone derivative, compound 5832, as a potent HBV inhibitor. In this study, we intend to elaborate the antiviral effect and mechanism of 5832 against HBV in vitro and in vivo.

DZ2002 alleviates corneal angiogenesis and inflammation in rodent models of dry eye disease via regulating STAT3-PI3K-Akt-NF-κB pathway.

Dry eye disease (DED) is a prevalent ocular disorder with a multifactorial etiology. The pre-angiogenic and pre-inflammatory milieu of the ocular surface plays a critical role in its pathogenesis. DZ2002 is a reversible type III S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor, which has shown excellent anti-inflammatory and immunosuppressive activities in vivo and in vitro.