Cardiotonic steroids (CTS) were first documented by ancient Egyptians more than 3000 years ago. Cardiotonic steroids are a group of steroid hormones that circulate in the blood of amphibians and toads and can also be extracted from natural products such as plants, herbs, and marines. It is well known that cardiotonic steroids reveal effects against congestive heart failure and atrial fibrillation; therefore, the term "cardiotonic" has been coined. Cardiotonic steroids are divided into two distinct groups: cardenolides (plant-derived) and bufadienolides (mainly of animal origin). Cardenolides have an unsaturated five-membered lactone ring attached to the steroid nucleus at position 17; bufadienolides have a doubly unsaturated six-membered lactone ring. Cancer is a leading cause of mortality in humans all over the world. In 2040, the global cancer load is expected to be 28.4 million cases, which would be a 47% increase from 2020. Moreover, viruses and inflammations also have a very nebative impact on human health and lead to mortality. In the current review, we focus on the chemistry, antiviral and anti-cancer activities of cardiotonic steroids from the naturally derived (toads) venom to combat these chronic devastating health problems. The databases of different research engines (Google Scholar, PubMed, Science Direct, and Sci-Finder) were screened using different combinations of the following terms: “cardiotonic steroids”, “anti-inflammatory”, “antiviral”, “anticancer”, “toad venom”, “bufadienolides”, and “poison chemical composition”. Various cardiotonic steroids were isolated from diverse toad species and exhibited superior anti-inflammatory, anticancer, and antiviral activities in in vivo and in vitro models such as marinobufagenin, gammabufotalin, resibufogenin, and bufalin. These steroids are especially difficult to identify. However, several compounds and their bioactivities were identified by using different molecular and biotechnological techniques. Biotechnology is a new tool to fully or partially generate upscaled quantities of natural products, which are otherwise only available at trace amounts in organisms.

Control of snail intermediate hosts has been proved to be a fast and efficient approach for interrupting the transmission of schistosomiasis. Some plant extracts have shown obvious molluscicidal activity, and a new compound Luo-Wei, also named tea-seed distilled saponin (TDS), was developed based on the saponins extracted from Camellia oleifera seeds. We aimed to test the molluscicidal activity of 4% TDS against the intermediate host snails in China and Egypt, and evaluate its environmental safety to non-target organisms. In the laboratory, Oncomelania hupensis, Biomphalaria alexandrina and Bulinus truncatus were exposed to 4% TDS, and the median lethal concentration (LC50) was estimated at 24, 48 and 72 h. In the field, snail mortalities were assessed 1, 2, 3 and 7 d post-immersion with 2.5 g/m3 4% TDS and 1, 3, 7 and 15 d post-spraying with 5 g/m2 4% TDS. In addition, the acute toxicity of 4% TDS to Japanese quail (Coturnix japonica), zebrafish (Brachydanio rerio) and freshwater shrimp (Macrobrachium nipponense) was assessed by estimations of LC50 or median lethal dose (LD50). In the laboratory, the LC50 values of 4% TDS for O. hupensis were 0.701, 0.371 and 0.33 mg/L at 24, 48 and 72 h, respectively, and 4% TDS showed a 1.975 mg/L 24 h LC50 against B. alexandrina, and a 1.396 mg/L 24 h LC50 against B. truncatus. Across all study regions, the pooled mortalities of O. hupensis were 72, 86, 94 and 98% at 1, 2, 3 and 7 d, following field immersion of 4% TDS at a dose of 2.5 g/m3, and were 69, 77, 85 and 88% at 1, 3, 7 and 15 d, following field spraying at 5 g/m2, respectively. 4% TDS had moderate toxicity to Japanese quail (7 d LD50 > 60 mg/kg) and to shrimp (96 h LC50 = 6.28 mg/L; 95% CI: 3.53–11.2 mg/L), whereas its toxicity to zebrafish was high (96 h LC50 = 0.15 mg/L; 95% CI: 0.14–0.17 mg/L). 4% TDS is active against O. hupensis, B. alexandrina and B. truncatus under laboratory and field conditions, and it may be a candidate molluscicide of plant origin.

Schistosomiasis is a common parasitic disease designated as a neglected tropical disease by the World Health Organization. Schistosomiasis mansoni is a form of the disease that is caused by the digenean trematode Schistosoma mansoni, transmitted through Biomphalaria spp. as an intermediate host. Biomphalaria was introduced to Hong Kong, China in aquatic plants shipments coming from Brazil and the snail rapidly established its habitats in southern China. Earlier studies of Biomphalaria spp. introduced to southern China identified the snails as Biomphalaria straminea, one of the susceptible species implicated in S. mansoni transmission in South America. However, recent molecular investigations also indicated the presence of another South American species, B. kuhniana, which is refractory to infection. As such, it is important to identify accurately the species currently distributed in southern China, especially with emerging reports of active S. mansoni infections in Chinese workers returning from Africa. We combined morphological and molecular taxonomy tools to precisely identify Biomphalaria spp. distributed in Guangdong Province, southern China. In order to clearly understand the molecular profile of the species, we constructed a phylogeny using mtDNA data (COI and 16S rRNA sequences) from six populations of Biomphalaria spp. from Shenzhen City in Guangdong Province. In addition, we examined the external morphology of the shell and internal anatomy of the reproductive organs. Both morphological and molecular evidences indicated a close affinity between Biomphalaria spp. populations from Guangdong and B. straminea from Brazil. The shell morphology was roughly identical in all the populations collected with rounded whorls on one side and subangulated on the other, a smooth periphery, an egg-shaped aperture bowed to one side, and a deep umbilicus. The shape and number of prostate diverticula (ranged from 11.67 to 17.67) in Guangdong populations supports its close affinity to B. straminea rather than B. kuhniana. Molecular analysis did not conflict with morphological analysis. Little genetic differentiation was observed within Biomphalaria populations collected. Phylogenetic analysis of COI and 16S rRNA haplotypes from snails collected and B. straminea sequences from Brazil and China using Bayesian inference revealed that Guangdong populations were clustered in one clade with B. straminea from Hong Kong of China and B. straminea from Brazil indicating their close affinity to each other. Data obtained in the current study clearly show that the populations of Biomphalaria spp. investigated are B. straminea, and we assume that those snails were either introduced via passive dispersal from Hong Kong of China or as a result of multiple introduction routes from Brazil.