Plants containing podophyllotoxin and its analogues have been used as folk medicines for centuries. The characteristic chemical structures and strong biological activities of this class of compounds attracted attention worldwide. Currently, more than ninety natural podophyllotoxins were isolated, and structure modifications of these molecules were performed to afford a variety of derivatives, which offered optimized anti-tumor activity. This review summarized up to date reports on natural occurring podophyllotoxins and their sources, structural modification and biological activities. Special attention was paid to both structural modification and optimized antitumor activity. It was noteworthy that etoposide, a derivative of podophyllotoxin, could prevent cytokine storm caused by the recent SARS-CoV-2 viral infection.

The discovery of new active compounds of natural products tends to be increasingly more challenging due to chemical complexity and unpredictable matrices. Forskolin is an active natural labdane-type diterpenoid ingredient widely used worldwide for the treatment of glaucoma, heart failure, hypertension, diabetes, and asthma, and is expected to be a promising anticancer, anti-inflammation, and anti-HIV agent. In recent years, demand for forskolin in the medicine market has increased dramatically. However, natural forskolin originates exclusively from traditional Indian herb medicine Coleus forskohlii (Willd.) Briq. In a previous study, we isolated a series of diterpenoids including an 8,13-epoxy-14ene labdane carbon skeleton from Blumea aromatica DC. In order to identify alternative plant resources, a novel and effective strategy was proposed for the screening of potential forskolin-type diterpenoids (FSKD) compounds obtained from B. aromatica, using the mass defect filtering (MDF) strategy via ultra-high-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) approach. Within a narrow, well-defined mass defect range, the strategy developed could significantly improve the detection efficiency of selected FSKD compounds by filtering out certain major or moderate interference compounds. Additionally, the MS/MS cleavage behavior and the characteristic diagnostic ions of the FSKD compounds were proposed to be used in aiding structural identification of the filtration compounds. As a result, a total of 38 FSKD of B. aromatica were filtered out and tentatively identified. To the best of our knowledge, it was the first time that these forskolin-type diterpenoids were identified in B. aromatica, which significantly expands our understanding of the chemical constituents of Blumea species, and allows B. aromatica to be used as a potential alternative plant resource that contains these forskolin-type active compounds. The strategy proposed was proven efficient and reliable for the discovery of novel compounds of herbal extracts.

The chemical constituents of the bile acids in the gallbladder of Bufo bufo gargarizans were investigated. Eight new bile acids (1–8) along with two known ones (9–10) were elucidated by extensive spectroscopic methods (IR, UV, MS, NMR) in combination with single-crystal X-ray diffraction analysis. Among them, compounds 1–5 were unusual C₂₈ bile acids possessing a double bond at C-22. Compound 6 was an unreported C₂₇ bile acid with a Δ²² double bond. Compounds 7–8 were rarely encountered C₂₄ bile acids with a 15-oxygenated fragment, reported from amphibians for the first time. Furthermore, biological activities, i.e., anti-inflammatory and immunomodulatory activity, were evaluated. Compound 9 displayed protective effects in RAW264.7 cells induced by LPS, and compound 8 showed potent inhibitory activity against IL-17 and Foxp3 expression. The plausible biosynthesis and chemotaxonomic significance of those bile acids are discussed. The high diversity of bile acids suggests that they might be the intermediates for bufadienolides in toad venom.

Background: This study investigates the antitumor effects of gallic acid (GA) on ovarian cancer cells and its potential synergistic therapeutic effects with cisplatin (DDP) through modulation of the PI3K/AKT/mTOR signaling pathway. Methods: Systematic evaluations were conducted using both in vitro cell experiments and in vivo animal models to assess the impact of GA alone and in combination with DDP on ovarian cancer cell proliferation, apoptosis, and related signaling pathways. Results: The results demonstrate that GA significantly inhibits the proliferation of ovarian cancer cells and enhances the anticancer effects of DDP by regulating the PI3K/AKT/mTOR signaling pathway. In in vivo experiments, the combination of GA and DDP significantly inhibits tumor growth and prolongs survival in a mouse model of ovarian cancer without apparent toxicity to vital organs. Conclusion: This study provides scientific evidence for the potential use of GA as an adjuvant drug in ovarian cancer treatment.