In our previous study, a screening of a variety of lycotonine-type diterpenoid alkaloids were screened for cardiotonic activity revealed that lycoctonine had moderate cardiac effect. In this study, a series of structurally diverse of lycoctonine were synthesized by modifying on B-ring, D-ring, E-ring, F-ring, N-atom or salt formation on lycoctonine skeleton. We evaluated the cardiotonic activity of the derivatives by isolated frog heart, aiming to identify some compounds with significantly enhanced cardiac effects, among which compound 27 with a N-isobutyl group emerged as the most promising cardiotonic candidate. Furthermore, the cardiotonic mechanism of compound 27 was preliminarily investigated. The result suggested that the cardiotonic effect of compound 27 is related to calcium channels. Patch clamp technique confirmed that the compound 27 had inhibitory effects on CaV1.2 and CaV3.2, with inhibition rates of 78.52 % ± 2.26 % and 79.05 % ± 1.59 % at the concentration of 50 μM, respectively. Subsequently, the protective effect of 27 on H9c2 cells injury induced by cobalt chloride was tested. In addition, compound 27 can alleviate CoCl2-induced myocardial injury by alleviating calcium overload. These findings suggest that compound 27 was a new structural derived from lycoctonine, which may serve as a new lead compound for the treatment of heart failure.

Four new compounds (1-4) were isolated from the whole plants of two species of Delphinium, including two C20-diterpenoid alkaloids, umbrodines A and B (1 and 2), and a dibenzoxazepinone, umbrolide A (3) from Delphinium umbrosum Hand.-Mazz. and a C20-diterpenoid alkaloid, kingiadine (4) from Delphinium kingianum Bruhl. ex Huth. Ten known diterpenoid alkaloids were also isolated. Their structures were elucidated via HR-ESIMS, IR, and NMR data. Lycoctonine (11) and delectinine (12) exhibited appreciable cardiac activity. Furthermore, 11 and 12 showed cardioprotective effects against doxorubicin-induced toxicity in H9c2 cells, with the maximum protection rates of 61.63% and 51.18%, respectively.

Two new 19-norbufadienolides (1 and 2) and one new 14,15-epoxy bufadienolide (3) alongside 16 known bufadienolides (4-19) were isolated from Bufonis Venenum that originated from the skin and parotid venom glands of an Asiatic toad (Bufo bufo gargarizans Cantor). The structures of these bufadienolides were elucidated based on the interpretation of their HRESIMS and NMR data. Compound 1, which had a unique peroxide, was established through extensive single-crystal X-ray diffraction. The two 19-norbufadienolides exhibited more potent cardiotonic activity in the isolated toad heart model and lower cytotoxicity against U87, U251, and LN-18 cell lines than other bufadienolides, such as bufalin and bufotalin. The results suggested that 19-norbufadienolides might be more suitable for developing cardiotonic agents with low cytotoxicity.

OBJECTIVE: Extract of Fagonia arabica, (family Zygophyllaceae) has thrombolytic activity against the clotted blood in blood vessels and the extract of Heteropneustes fossilis shows the cardiotonic activity. Therefore, combinatory pharmacology shows the synergistic activity in tied mice for a long duration.
METHODS: The cardiotonic activity of Heteropneustes fossilis fish extract was examined on a frog intact heart and then pharmacologically performed on 20 mice without plant extract as well as with a combination of plant extract, which gave a remarkable synergistic activity in an in-vivo experiment on mice kept tied for the duration of 12, 18, and 24 hours and injected within one minute after untying. RESULT AND DISCUSION: The plant extract was compared with streptokinase as well as a non-thrombolytic agent (control). A study showed a percentage of clot lysis, which was 65.5% for plant extract, but streptokinase had 71%. The study was done in 11 healthy volunteers representing a mean value and SD of 65% ± 2.01% and 71.67% ± 0.71% of the plant extract and streptokinase, respectively, in contrast to the non-thrombolytic (control), that is, 0.86% ± 0.08%.
CONCLUSIONS: Injection of plant and fish extract acts both synergistically in the blood clotted mice and in mice suffering from myocardial or cerebral infarction and embolized mice.