The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

Inflammation plays a pivotal role in the etiology and progression of various diseases. In traditional Chinese medicine, the whole plants of Thesium chinense Turcz. and its preparations (e.g. Bairui Granules) have been employed to manage inflammatory conditions. While flavonoids were previously considered the primary anti-inflammatory components, other potentially active constituents have been largely overlooked and not thoroughly investigated. This study presents a novel finding that the total alkaloids of T. chinense (BC-Alk) are potent active substances underlying the traditional and clinical applications of T. chinense and Bairui Granules as anti-inflammatory agents. UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids. The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide (LPS)-induced lung inflammation model in mice. Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation, attenuated the overproduction of IL-1β and the overproduction of inflammatory factors (TNF-α), and ameliorated lung tissue hyperplasia in mice in vivo. Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit (GCLM), inhibited NF-κB phosphorylation, and suppressed NLRP3 activation. Collectively, these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2, NF-κB, and NLRP3 pathways. This study provides new insights into the anti-inflammatory constituents of T. chinense and Bairui Granules.
Animals ; Lipopolysaccharides/adverse effects* ; Alkaloids/pharmacology* ; NF-kappa B/metabolism* ; NF-E2-Related Factor 2/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Male ; Mice, Inbred C57BL ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Pneumonia/genetics*

It is critical to regulate the senescence-associated secretory phenotype (SASP) due to its effect on promoting malignant phenotypes and limiting the efficiency of cancer therapy. In this study, we demonstrated that marchantin M (Mar-M, a naturally occurring bisbibenzyl) suppressed pro-inflammatory SASP components which were elevated in chemotherapy-resistant cells. Mar-M treatment attenuated the pro-tumorigenic effects of SASP and enhanced survival in drug-resistant mouse models. No toxicity was detected on normal fibroblast cells or in animals following this treatment. Inactivation of transcription factor EB (TFEB) and nuclear factor-B (NF-B) by Mar-M significantly accounted for its suppression on the components of SASP. Furthermore, inhibition of SASP by Mar-M contributed to a synergistic effect during co-treatment with doxorubicin to lower toxicity and enhance antitumor efficacy. Thus, chemotherapy-driven pro-inflammatory activity, seen to contribute to drug-resistance, is an important target for Mar-M. By decreasing SASP, Mar-M may be a potential approach to overcome tumor malignancy.

Objective To prepare the curcumin self-microemulsion, observe the morphology and size diameter distribution of the microemulsion, and compare the absorption kinetics of curcumin microemulsion and micelle. To investigate the best absorption segment of curcumin microemulsion in intestnum tenue and the absorption of curcumin self-microemulsion in mouse gastrointestinal tract. MethodsThe intestine in rats was cannulated in situ recirculation. The absorption of curcumin microemulsion was calculated by its decrement in intestnum tenue.The inabsorbable curcumin in all content together with feces in mouse gastrointestinal tract was obtained and used to calculate the absorption rate of curcumin. ResultsThe curcumin microemulsion presented as small spherical drops or something similar under transmission electron microscope (TEM) with the average diameter of about 21.6 nm. The absorption constants of curcumin microemulsion and micelle was 0.042 5 and 0.019 5 /h , the main segments of curcumin microemulsion absorption were intestinum duodenum and intestinum jejunum. The absorption rate of curcumin self-microemulsion was 2.5 times as much as curcumin. ConclusionThe curcumin self-microemulsion could improve the absorption of curcumin in vivo in animal evidently.

From the water soluble extract of Flos Lonicera japonica Thunb.,three triterpenoid saponins were isolated. On the basis of detailed analysis of 1HNMR, 13CNMR, 1H-1HCOSY, HMBC, HMQC, FAB MS, their structures were decided as 3-O-?- L-rhamnopyranosyl-(1→2)-?-L-arabinopyranosyl hederagenin 28-O-?-Dxylpyranosyl (1→6 )-?-D-glucopyranosyl ester (Ⅰ), 3-O-?-L-arabinopyranosyl hederagenin 28-O-?-L-rhamnopyranosyl (1→2) [?-D-xylpyranosyl (1→6)] -?-glucopyranosyl ester (Ⅱ) a nd 3-O-?-L-rhamnopyranosyl (1→2) -?-L-arabinopyranosyl hederagenin 28-O-?-L-rhamnopyranosyl (1→2)[?-D-xylpyranosyl (1→6)]?-D-glucopyranosyl ester（Ⅲ), and chlorogenin tetraacetate (Ⅳ). Pharmacological experiment showed thatthese compounds had cytoprotective effects against carbon tetrachloride induced hepatic injury.

Object To study the chemical constituents of Frullania muscicola Steph (Frullaniaceae) Methods Seven compounds were obtained from the petroleum ether extract of F muscicola by repeated chromatography over silica gel and Sephadex LH 20 Their structures were identified by analysis of their spectral data and chemical reactions Results Three steroids and four flavonoids had been isolated and their structures were identified as: stigmasterol arachidate (Ⅰ), sitosterol (Ⅱ), apigenin 7, 4′ dimethyl ethers (Ⅲ), scutellarin 6, 4′ dimethyl ethers (Ⅳ), 6 hydroxyluteolin 6, 3′ dimethyl ethers (Ⅴ), scutellarin 6 methyl ether (Ⅵ), and daucosterol (Ⅶ) Conclusion Compound I was new and the other six were obtained from this plant for the first time