Although the wide variety of bioactivities of curcumin has been reported by researchers, the clinical application of curcumin is still limited due to its poor aqueous solubility. In view of this, a series of dimethylaminomethyl-substituted curcumin derivatives were designed and synthesized (compounds 1–15). Acetate of these derivatives were prepared (compounds 1a–15a). The Mannich reaction and aldol condensation reaction are the main reactions involved in this study. Compounds 6, 10, 12, 3a, 5a, 6a, 7a, 8a, 10a, 11a, 12a, 13a, 14a, and 15a exhibited better in vitro anti-inflammatory activity compared to curcumin in the RAW264.7 cell line. Compounds 5, 1a, 5a, 8a, and 12a exhibited better in vitro antioxidant activity compared to curcumin in the PC 12 cell line. Compounds 11, 13, 5a, 7a, and 13a exhibited better in vitro radiation protection compared to curcumin in the PC 12 cell line. The aqueous solubilities of all the curcumin derivative acetates were greatly improved compared to curcumin.

Chinese herbs are a huge treasure trove of natural products and an important source of many active molecules. The theory of traditional Chinese medicine compatibility (TCMC) is widely applied in clinical practice, but its mechanism is still ambiguous. This study aims to open a new window for this predicament by studying the interaction between the main active ingredients from a drug pair. Carrier-free assembly of natural products improves the shortcomings of traditional nanodelivery systems and opens a new path for the development of new nanomaterials. The drug pair “Pueraria and Hedyotis diffusa” has been commonly used in clinical practice, with a predominant therapeutic effect. This study is devoted to the study of the binary small molecule co-assembly of the main active molecules from the drug pair. In this study, we introduce a carrier-free composite gel, formed by the co-assembly of puerarin (PUE) and deacetylasperulosidic acid (DAA) via non-covalent bonds including π–π packing, intermolecular hydrogen bonding, and C=O π interactions. With a strain point 7-fold higher than that of P gel, the P − D gel exhibited favorable rheological properties. The survival rate of SW1990 cells in the P − D group was only 21.39% when the concentration of administration reached 200 μM. It thus demonstrated activity in inhibiting SW1990 cells’ survival, suggesting potential in combating pancreatic cancer. Furthermore, this research offers a valuable concept for enhancing the mechanical properties and bioactivity of hydrogel materials through the utilization of a multi-component natural small molecule co-assembly approach. More importantly, this provides new ideas and methods for the treatment of pancreatic cancer and the analysis of traditional Chinese medicine compatibility theory.

Two new compounds, ardisiapunine B (1) and ardisiapunine C (2), were isolated from Ardisia lindleyana D. Dietr. Their structures were examined using HR–ESI–MS, IR, (1D, 2D) NMR spectroscopic analyses, single–crystal X–ray diffraction, and ECD calculation. It was found that the two new compounds belong to unusual oleanane-type triterpenes, with compound 1 bearing an acetal unit and a C–13–C–18 double bond, and compound 2 bearing a C–28 aldehyde group and a C–18–C–19 double bond. The anti-inflammatory properties of compounds 1 and 2 were tested on NO production and cellular morphology using RAW264.7 cells, and their anti-tumor properties were tested on cytotoxic activities, cellular morphology, cell apoptosis, and cell cycle. The results showed that compound 1 exhibited a potent cytotoxicity against HepG2 cell lines with an IC₅₀ of 12.40 μM. Furthermore, it is possible that compound 1 inhibits cell proliferation by blocking the cell G2/M phase and promoting cell apoptosis. Compound 2 exhibited a potential anti-inflammatory activity by decreasing the production of NO in LPS–stimulated RAW264.7 cells. Comparative analysis of the structures of compounds 1 and 2 revealed that the acetal structure and double bond positions were the main differences between them, and these are presumed to be the main reasons for the extreme differences in their cytotoxicity and anti-inflammatory activities. From these new findings, two promising lead compounds were identified for the future development of potential anti–inflammatory or anti–tumor agents.

Alkaloids are a material treasure bestowed on humans by nature owing to their numerous biological activities. Orychophragine D, an alkaloid isolated from the seeds of Orychophragmus violaceus was identified as bearing a novel skeleton and proved to have an excellent radioprotective effect. Different from the common alkaloid structure, the main block of orychophragine D is constructed of an oxotriazine and an oxopiperazine, which are connected in parallel by a C-N bond. In this paper, a preparation method for the novel heterocycle skeleton of orychophragine D is proposed for the first time. N-Boc-L-serine was utilized as the original material to complete the preparation with 11 steps in a 13% overall yield. A hydroxyl group was established on the side chain of the skeleton as the reaction site for researchers to conduct further structural modification or derivatization.

3,4-dihydroxybenzenesulfonyl-functionalized polyethyleneimine (PS), a novel polymeric chelator, was synthesized by conjugating 3,4-dihydroxybenzenesulfonyl (CAM) groups with branched polyethyleneimine (BPEI, MW = 600 Da) via N-acylation. PS demonstrated a high uranium adsorption capacity of 78.08% at a concentration of 4 mg/mL, accompanied by significant selectivity over competing ions such as Ca²⁺, Zn²⁺, and Cu²⁺. Notably, in competitive adsorption experiments, PS exhibited a uranium adsorption rate of 59.49%, which was 3.95 times higher than that of calcium (15.06%) in the Ca²⁺ system. Cytotoxicity assays revealed enhanced biocompatibility (IC₅₀ = 86.98 μg/mL), surpassing CaNa₃-DTPA 3.7-fold. In a uranium exposure model (200 μg/mL), PS significantly improved cell survival rates and reduced intracellular uranium levels by 77.37% (immediate administration) and 64.18% (delayed administration). These findings establish PS as a potent and safe polymeric chelator for uranium decorporation, offering a promising strategy for mitigating the hazards of radioactive materials.

Irradiation (IR) can cause intestinal epithelial cell death, damage to crypt stem cells, and mucosal barrier dysfunction, which are the features of radiation-induced intestinal injury (RIII). Our study first discovered a natural small-molecule alkaloid Orychophragine D (OV16) with an obvious radiation protection effect. This study aims to investigate the radiation protection effect of OV16 on RIII and its potential molecular mechanism. The results showed that in vitro OV16 exhibited a significant protective effect on an irradiated human small intestinal epithelial cell-6 (HIEC-6) model. Then, transglutaminase 2 (TGM2), which is the key protein for OV16 to exert its anti-RIII protective effect, was identified as a crucial cellular target of OV16 using drug affinity responsive target stability (DARTS), molecular docking, molecular dynamics simulation, cell thermal shift assay (CETSA), and microscale thermophoresis (MST). Moreover, OV16 can upregulate the expression level of TGM2 in the nucleus of HIEC-6. TGM2 can reduce radiation-induced damage by enhancing the proliferation ability and migration ability of HIEC-6 and reducing the generation of γ-H2AX. Collectively, our study first identified TGM2 as a previously unreported therapeutic target for RIII, and provided a future drug design direction for TGM2 allosteric activators using OV16 as a novel molecular template.