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Simple Summary: Green healthcare relates to using naturally derived sources as medicines to treat and personalize treatments for various diseases. Cancer is one primary global health concern due to its rapid evolution and high prevalence, especially lung cancer. Cinobufagin (CB), a bufadienolide derived primarily from the parotid glands of frogs, has shown promise in combating lung cancer. Our objective with this systematic review is to synthesize the current evidence on CB's effects against lung cancer, focusing on its mechanisms of action, efficacy, and potential clinical implications. Our results indicated that CB reduces lung cancer tumor growth via increased apoptosis by reducing cancer cells' viability. In addition, CB also has impacted migration and invasion across multiple lung cancer cell lines and xenograft models. The molecular pathways involved Bcl-2, Bax, cleaved caspases, caveolin-1, FLOT2, Akt, STAT3, and FOXO1. CB achieved these effects with minimal toxicity. Cinobufagin (CB), a bufadienolide, has shown promising potential as an anticancer agent, particularly in combating lung cancer. This systematic review synthesizes preclinical evidence on CB's effects against lung cancer, focusing on its mechanisms of action, efficacy, and potential clinical implications. We analyzed data from various preclinical studies involving both in vitro cell line models and in vivo animal models. The reviewed studies indicate that CB effectively reduces cell viability, induces apoptosis, and inhibits cell proliferation, migration, and invasion across multiple lung cancer cell lines and xenograft models. Specifically, CB was found to decrease cell viability and increase apoptosis in lung cancer cells by modulating key molecular pathways, including Bcl-2, Bax, cleaved caspases, caveolin-1, FLOT2, Akt, STAT3, and FOXO1. In vivo studies further demonstrated significant inhibition of tumor growth with minimal toxicity. However, limitations include reliance on in vitro models, which may not fully represent in vivo tumor dynamics, and a lack of long-term safety data. The studies also vary in their methodologies and cell line models, which may not accurately encompass all lung cancer subtypes or predict human responses. Despite these limitations, CB's ability to target specific molecular pathways and its promising results in preclinical models suggest it could be a valuable addition to lung cancer treatment strategies. Our review suggests further clinical trials to validate its efficacy and safety in humans. Future research should explore combination therapies and optimize delivery methods to enhance clinical outcomes. [ABSTRACT FROM AUTHOR]

The nuchal glands are organs of chemical defense embedded under the skin of several species of Rhabdophis and contain toxins sequestered from consumed prey. Rhabdophis subminiatus possesses nuchal glands, but not much information is available on its toxin source and prey preference, particularly based on its chemosensory response. We hypothesized that the response of R. subminiatus toward toads would be higher than other potential prey because the snake needs to sequester toxins contained in toad skin. We also examined the snake preference toward several bufonid species to test a hypothesis that the preference toward Duttaphrynus melanostictus is higher than other toad species due to its high availability in the habitat of the snake. To test the hypotheses, we conducted chemical response tests and compared the tongue-flick attack score (TFAS) of the snake toward prey chemical stimuli. The first experiment used only one toad species (D. melanostictus) and various potential prey animals for the source of chemical stimuli. The second experiment used chemical stimuli from several species of frogs and toads. In the first experiment, snakes showed the highest response toward D. melanostictus. However, in the second experiment, snakes showed the highest response toward a toad, Ingerophrynus biporcatus, followed by D. melanostictus, and a lower response toward another toad, Phrynoidis asper. These results indicate that the snake has a high preference toward toads, but its preference varies among toad species. Taken together, this study suggests that R. subminiatus discriminates different potential prey chemical cues and probably consumes toads to sequester their toxins. [ABSTRACT FROM AUTHOR]

A new xanthone glycoside (1) and a new bufadienolide (2) named bersamaxanthoside and bersamabufadienolide, respectively, together with seventeen known compounds (3 – 19) were isolated from the stem bark of Bersama abyssinica Fresen subsp. abyssinica Verdc. Their structures were elucidated based on their spectroscopic data. The extract, fractions and compounds were assessed for their cytotoxicity on the cervix carcinoma cell line KB-3–1. The MeOH extract and the EtOAc and n-BuOH soluble fractions exhibited weak activity with IC 50 values of 0.085, 0.084 and 0.075 mg/mL, respectively. The other tested samples were inactive. In addition, some of the isolates were tested for their DPPH radical scavenging activity and only compounds 1 , 11–13 , 16 , and 17 displayed antioxidant properties with IC 50 values ranging from 2.9 to 38.1 µg/mL. [Display omitted] • A new xanthone glycoside and a new bufadienolide from Bersama abyssinica stem bark. • A lignan and a benzoquinone are firstly reported form the genus Bersama. • The cytotoxicity and DPPH radical scavenging activities of extracts and isolates. [ABSTRACT FROM AUTHOR]

Insects are incapable of biosynthesising sterols de novo so they need to obtain them from their diets or, in certain cases, from symbiotic microorganisms. Sterols serve a structural role in cellular membranes and act as precursors for signalling molecules and defence compounds. Many phytophagous insects dealkylate phytosterols to yield primarily cholesterol, which is also the main sterol that carnivorous and omnivorous insects obtain in their diets. Some phytophagous species have secondarily lost the capacity to dealkylate and consequently use phytosterols for structural and functional roles. The polyhydroxylated steroid hormones of insects, the ecdysteroids, are derived from cholesterol (or phytosterols in non-dealkylating phytophagous species) and regulate many crucial aspects of insect development and reproduction by means of precisely regulated titres resulting from controlled synthesis, storage and further metabolism/excretion. Ecdysteroids differ significantly from vertebrate steroid hormones in their chemical, biochemical and biological properties. Defensive steroids (cardenolides, bufadienolides, cucurbitacins and ecdysteroids) can be accumulated from host plants or biosynthesised within the insect, depending on species, stored in significant amounts in the insect and released when it is attacked. Other allelochemical steroids serve as pheromones. Vertebrate-type steroids have also been conclusively identified from insect sources, but debate continues about their significance. Side chain dealkylation of phytosterols, ecdysteroid metabolism and ecdysteroid mode of action are targets of potential insect control strategies., (© 2024. All color figures to remain in the eBook and to be printed in color.)

Bufadienolides are digitalis-like aglycones mainly found in skin secretions of toads. Among their biological properties, the mechanisms of antiproliferative action on tumor cells remain unclear for many compounds, including against leukemia cells. Herein, it was evaluated the mechanisms involved in the antiproliferative and genotoxic actions of hellebrigenin on tumor cell lines and in silico capacity to inhibit the human topoisomerase IIa enzyme. Firstly, its cytotoxic action was investigated by colorimetric assays in human tumor and peripheral blood mononuclear cells (PBMC). Next, biochemical and morphological studies were detailed by light microscopy (trypan blue dye exclusion), immunocytochemistry (BrdU uptake), flow cytometry and DNA/chromosomal damages (Cometa and aberrations). Finally, computational modelling was used to search for topoisomerase inhibition. Hellebrigenin reduced proliferation, BrdU incorporation, viability, and membrane integrity of HL-60 leukemia cells. Additionally, it increased G 2 /M arrest, internucleosomal DNA fragmentation, mitochondrial depolarization, and phosphatidylserine externalization in a concentration-dependent manner. In contrast to doxorubicin, hellebrigenin did not cause DNA strand breaks in HL-60 cell line and lymphocytes, and it interacts with ATPase domain residues of human topoisomerase IIa, generating a complex of hydrophobic and van der Waals interactions and hydrogen bonds. So, hellebrigenin presented potent anti-leukemic activity at concentrations as low as 0.06 μM, a value comparable to the clinical anticancer agent doxorubicin, and caused biochemical changes suggestive of apoptosis without genotoxic/clastogenic-related action, but it probably triggers catalytic inhibition of topoisomerase II. These findings also emphasize toad steroid toxins as promising lead antineoplasic compounds with relatively low cytotoxic action on human normal cells. [Display omitted] • Hellebrigenin has antiproliferative action comparable to the clinical drug doxorubicin. • It reduces cell division, viability, and membrane integrity of HL-60 leukemia cells. • It causes arrest in G 2 /M, DNA fragmentation, and phosphatidylserine externalization. • It interacts with ATPase domain residues of human Topoisomerase IIa. • Anti-dividing action of hellebrigenin is not linked to genotoxic/clastogenic effects. [ABSTRACT FROM AUTHOR]