Steroid and triterpenoid saponins from the rhizomes of Paris polyphylla var. stenophylla.

Five new saponins, including three steroid saponins, paristenoids A-C (1-3), and two triterpenoid saponins, paristenoids D-E (4-5), along with four known ones (6-9) were isolated from the rhizomes of Paris polyphylla var. stenophylla. The structures of the isolated compounds were identified mainly by detailed spectroscopic analysis, including extensive 1D and 2D NMR, MS, as well as chemical methods. Compound 3 is a new cyclocholestanol-type steroidal saponin with a rare 6/6/6/5/5 fused-rings cholestanol skeleton, and this skeleton has been first found from the genus Paris. The cytotoxicities of the isolated compounds against three human three glioma cell lines (U87MG, U251MG and SHG44) were evaluated, and compound 7 displayed certain inhibitory effect with IC50 values of 15.22 ± 1.73, 18.87 ± 1.81 and 17.64 ± 1.69 µmol·L-1, respectively.

Effects of taurine on rumen fermentation, nutrient digestion, rumen bacterial community and metabolomics and nitrogen metabolism in beef steers.

BACKGROUND: The objectives of this study were to investigate the effects of taurine on rumen fermentation, rumen bacterial community and metabolomics, nitrogen metabolism and plasma biochemical parameters in beef steers. Six castrated Simmental steers (liveweight 402 ± 34 kg) and three levels of taurine (0, 20, 40 g d-1 ) were assigned in a replicated 3 × 3 Latin square design. Each experimental period included 15 days for adaptation and 5 days for sampling. RESULTS: Supplementing taurine did not affect the ruminal pH or concentrations of ammonia nitrogen and volatile fatty acids (P > 0.10), but linearly increased the ruminal concentrations of taurine (P < 0.001) and microbial crude protein (P = 0.041). Supplementing taurine linearly increased the neutral detergent fiber digestibility (P = 0.018), and tended to linearly increase dry matter digestibility (P = 0.095), tended to increase the fecal nitrogen excretion (P = 0.065) and increased the urinary taurine excretion (P < 0.001). Supplementing taurine quadratically increased the plasma concentration of triglycerides (P = 0.017), tended to linearly decrease growth hormone (P = 0.074), but did not affect other plasma parameters (P > 0.10). Supplementing taurine modified the rumen bacterial community and increased the ruminal concentration of taurine metabolite 2-hydroxyethoxysulfonic acid (P < 0.001). CONCLUSION: It was concluded that taurine improved ruminal microbial crude protein synthesis and increased fiber digestibility through modifying rumen bacterial community. It is necessary to clarify the ruminal hydrolysis of taurine in steers. © 2023 Society of Chemical Industry.

Nitric-Oxide-Releasing aza-BODIPY: A New Near-Infrared J-Aggregate with Multiple Antibacterial Modalities.

The development of near-infrared (NIR) J-aggregates has received increasing attention due to their broad applications. Here, we report the nitrosation of an amine-containing aza-BODIPY precursor (BDP-NH2 ), affording the first nitric oxide (NO)-releasing NIR J-aggregate (BDP-NO). The introduction of N-nitrosamine moieties efficiently inhibits the aromatic interactions of BDP-NH2 , which instead promotes the formation of J-aggregates within micellar nanoparticles with a remarkable bathochromic shift of ≈109 nm to the NIR window (820 nm). Interestingly, the NO release and photothermal conversion efficiency (PTCE) can be delicately tuned by the loading contents of BDP-NO within micellar nanoparticles, thereby enabling multiple antibacterial modalities by exploring either NO release, photothermal therapy (PTT), or both. We demonstrate the combination of NO and PTT can elevate antibacterial activity while attenuating PTT-associated inflammation for the in vivo treatment of MRSA infection.

Orchestrating Nitric Oxide and Carbon Monoxide Signaling Molecules for Synergistic Treatment of MRSA Infections.

The local delivery of gaseous signaling molecules (GSMs) has shown promising therapeutic potential. However, although GSMs have a subtle interplay in physiological and pathological conditions, the co-delivery of different GSMs for therapeutic purposes remains unexplored. Herein, we covalently graft a nitric oxide (NO)-releasing N-nitrosamine moiety onto the carbon monoxide (CO)-releasing 3-hydroxyflavone (3-HF) antenna, resulting in the first NO/CO-releasing donor. Under visible light irradiation, photo-mediated co-release of NO and CO reveals a superior antimicrobial effect toward Gram-positive bacteria with a combination index of 0.053. The synergy of NO and CO hyperpolarizes and permeabilizes bacterial membranes, which, however, shows negligible hemolysis and no evident toxicity toward normal mammalian cells. Moreover, the co-release of NO and CO can efficiently treat MRSA infection in a murine skin wound model, showing a better therapeutic capacity than vancomycin.

Red-Light-Mediated Photoredox Catalysis Enables Self-Reporting Nitric Oxide Release for Efficient Antibacterial Treatment.

Nitric oxide (NO) serves as a key regulator of many physiological processes and as a potent therapeutic agent. The local delivery of NO is important to achieve target therapeutic outcomes due to the toxicity of NO at high concentrations. Although light stimulus represents a non-invasive tool with spatiotemporal precision to mediate NO release, many photoresponsive NO-releasing molecules can only respond to ultraviolet (UV) or near-UV visible light with low penetration and high phototoxicity. We report that coumarin-based NO donors with maximal absorbances at 328 nm can be activated under (deep) red-light (630 or 700 nm) irradiation in the presence of palladium(II) tetraphenyltetrabenzoporphyrin, enabling stoichiometric and self-reporting NO release with a photolysis quantum yield of 8 % via photoredox catalysis. This NO-releasing platform with ciprofloxacin loading can eradicate Pseudomonas aeruginosa biofilm in vitro and treat cutaneous abscesses in vivo.

Rationally Engineering Phototherapy Modules of Eosin-Conjugated Responsive Polymeric Nanocarriers via Intracellular Endocytic pH Gradients.

Spatiotemporal switching of respective phototherapy modes at the cellular level with minimum side effects and high therapeutic efficacy is a major challenge for cancer phototherapy. Herein we demonstrate how to address this issue by employing photosensitizer-conjugated pH-responsive block copolymers in combination with intracellular endocytic pH gradients. At neutral pH corresponding to extracellular and cytosol milieu, the copolymers self-assemble into micelles with prominently quenched fluorescence emission and low (1)O2 generation capability, favoring a highly efficient photothermal module. Under mildly acidic pH associated with endolysosomes, protonation-triggered micelle-to-unimer transition results in recovered emission and enhanced photodynamic (1)O2 efficiency, which synergistically actuates release of encapsulated drugs, endosomal escape, and photochemical internalization processes.