The Potential Mechanisms by which Artemisinin and Its Derivatives Induce Ferroptosis in the Treatment of Cancer

Artemisinin (ART) is a bioactive molecule derived from the Chinese medicinal plant Artemisia annua (Asteraceae). ART and artemisinin derivatives (ARTs) have been effectively used for antimalaria treatment. The structure of ART is composed of a sesquiterpene lactone, including a peroxide internal bridge that is essential for its activity. In addition to their well-known antimalarial effects, ARTs have been shown recently to resist a wide range of tumors. The antineoplastic mechanisms of ART mainly include cell cycle inhibition, inhibition of tumor angiogenesis, DNA damage, and ferroptosis. In particular, ferroptosis is a novel nonapoptotic type of programmed cell death. However, the antitumor mechanisms of ARTs by regulating ferroptosis remain unclear. Through this review, we focus on the potential antitumor function of ARTs by acting on ferroptosis, including the regulation of iron metabolism, generation of reactive oxygen species (ROS), and activation of endoplasmic reticulum stress (ERS). This article systematically reviews the recent progress in ferroptosis research and provides a basis for ARTs as an anticancer drug in clinical practice.

Absolute Configuration Determination of Two Diastereomeric Neovasifuranones A and B from Fusarium oxysporum R1 by a Combination of Mosher’s Method and Chiroptical Approach

Endophytic fungi are one of prolific sources of bioactive natural products with potential application in biomedicine and agriculture. In our continuous search for antimicrobial secondary metabolites from Fusarium oxysporum R1 associated with traditional Chinese medicinal plant Rumex madaio Makino using one strain many compounds (OSMAC) strategy, two diastereomeric polyketides neovasifuranones A (3) and B (4) were obtained from its solid rice medium together with N-(2-phenylethyl)acetamide (1), 1-(3-hydroxy-2-methoxyphenyl)-ethanone (2) and 1,2-seco-trypacidin (5). Their planar structures were unambiguously determined using 1D NMR and MS spectroscopy techniques as well as comparison with the literature data. By a combination of the modified Mosher’s reactions and chiroptical methods using time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) and optical rotatory dispersion (ORD), the absolute configurations of compounds 3 and 4 are firstly confirmed and, respectively, characterized as (4S,7S,8R), (4S,7S,8S). Bioassay results indicate that these metabolites 1–5 exhibit weak inhibitory effect on Helicobacter pylori 159 with MIC values of ≥16 μg/mL. An in-depth discussion for enhancement of fungal metabolite diversity is also proposed in this work.

Rhizospheric Fungal Diversities and Soil Biochemical Factors of Fritillaria taipaiensis over Five Cultivation Years

Fritillaria taipaiensis is a valuable traditional Chinese medicinal plant that has experienced continuous decline over its cropping area. The present study aims to explore the reasons for the quality and growth decline. The fungal diversities and biochemical factors in its rhizospheric soils with cultivation duration from 1 up to 5 years were analyzed and compared. The results showed that rhizospheric fungi of F. taipaiensis belong to six phyla, including Neocallimastigomycota, Glomeromycota, Basidiomycota, Chytridiomycota, Zygomycota and Ascomycota. Thirteen genera (Pseudogymnoascus, Fusarium, Mortierella, Colletotrichum, Laetinaevia, Gibberella, Synchytrium, Lysurus, Trichocladium, Volutella, Monoblepharis, Aquamyces and Trichoderma) constituted the “core community” in the rhizosphere of F. taipaiensis. The dominant fungal genera varied significantly in rhizospheric soils with different cultivation years. The abundance of fungal species in the soil declined with the cultivation year generally. The pH, available P, organic matter and urease activity were the primary factors determining the fungal community composition in the rhizosphere. The content of organic matter, available N, P and K and the activities of urease and alkaline phosphatase decreased with cultivation years. The soil pH increased with cultivation years and was unsuitable for F. taipaiensis growth. These features suggested that long-term single planting altered the fungal community structure, fertility conditions and soil enzyme activities in F. taipaiensis rhizospheric soils, which could be detrimental for plant growth and quality.

The Effect of Microbial Fertilizer on the Growth, Rhizospheric Environment and Medicinal Quality of Fritillaria taipaiensis

Fritillaria taipaiensis is a valuable traditional Chinese medicinal plant affected by germplasm degradation during cultivation. To find a suitable solution for this problem, F. taipaiensis was inoculated with exogenous arbuscular mycorrhiza (AM) fungi, potassium-solubilizing bacteria, and phosphorus-solubilizing bacteria in pot experiments. The effects of inoculation on the AM colonization, photosynthetic pigment, and superoxide dismutase contents, rhizospheric enzyme activities, alkaloid, and nucleotide content of F. taipaiensis were studied. The results showed that the inoculation increased mycorrhizal infection intensity of F. taipaiensis. Compared to the control group, the photosynthetic pigment contents in the leaf of the inoculation groups were increased; the content of soluble protein, the activities of the superoxide dismutase, catalase, and peroxidase in leaves were all significantly increased, and the content of malondialdehyde was decreased. The microbial inoculum also increased the content of active ingredients in F. taipaiensis bulbs and increased the enzyme activities, total microorganism number, bacteria/fungi, and actinomycetes/fungi ratios in the rhizosphere. To sum up, microbial fertilizer can significantly improve the rhizospheric environment and medicinal quality of F. taipaiensis. This research provides a theoretical basis and experimental evidence for the sustainable development of an F. taipaiensis industry.

Intra-Articular Injection of a Nanosuspension of Tetramethylpyrazine Dihydroxynaphthalenate for Stronger and Longer-Lasting Effects Against Osteoarthritis

Tetramethylpyrazine (TMP), isolated from the rhizome of the traditional Chinese medicinal plant Chuanxiong (Ligusticum wallichii Franchat) shows therapeutic efficacy against osteoarthritis. After intra-articular injection, the retention time of TMP in the joint cavity is short, which limits its treatment effect. To avoid this problem, the present study explored the preparation of a TMP nanosuspension (TMP-NS) based on hydrophobic ion pairing. TMP-NS showed a particle size of approximately 588 nm and, after intra-articular injection in rats, it had longer retention in the articular cavity, higher TMP concentrations in joints, and greater anti-osteoarthritic efficacy than TMP solution. TMP-NS didn’t cause significant inflammation at the joint. These results suggest that TMP-NS may strengthen and prolong the therapeutic efficacy of TMP against osteoarthritis without systemic toxicity.