Steroidal alkaloids have organic ring backbones which feature nitrogen-based functional groups. More specifically, they are distinguished by their tetracyclic cyclopentanophenanthrene backbone that marks their close relationship with

sterol Sterol is an organic compound with formula , whose molecule is derived from that of gonane by replacement of a hydrogen atom in position 3 by a hydroxyl group. It is therefore an alcohol of gonane. More generally, any compounds that contain the go ...

s. They fall in two major categories: Solanum alkaloids and Veratrum alkaloids. A Steroidal alkaloid has also been found in ''

Chonemorpha fragrans ''Chonemorpha fragrans'', the frangipani vine or climbing frangipani, is a plant species in the genus '' Chonemorpha''. It is a vigorous, generally evergreen, climbing shrub producing stems or more long that can climb to the tops of the tallest ...

'' (Frangipani vine), 'chonemorphine' was used to treat intestinal infections in

Wistar rats A laboratory rat or lab rat is a brown rat of the subspecies '' Rattus norvegicus domestica'' which is bred and kept for scientific research. While less commonly used for research than mice (see laboratory mouse), rats have served as an importa ...

. (Chatterjee DK et al (1987) Parasitol Res 74, 1, 30-33).

''Solanum'' alkaloids

These compounds generally appear as their corresponding

glycoside In chemistry, a glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. ...

in plants of the genus ''Solanum''. ''Solanum'' includes plants like

potato The potato is a starchy food, a tuber of the plant ''Solanum tuberosum'' and is a root vegetable native to the Americas. The plant is a perennial in the nightshade family Solanaceae. Wild potato species can be found from the southern Unit ...

es,

tomato The tomato is the edible berry of the plant ''Solanum lycopersicum'', commonly known as the tomato plant. The species originated in western South America, Mexico, and Central America. The Mexican Nahuatl word gave rise to the Spanish word ...

es, and various nightshades Starting with cholesterol, the biosynthesis of these compounds follow a similar general mechanism including

hydroxylation In chemistry, hydroxylation can refer to: *(i) most commonly, hydroxylation describes a chemical process that introduces a hydroxyl group () into an organic compound. *(ii) the ''degree of hydroxylation'' refers to the number of OH groups in a ...

oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...

, and transamination before differentiating. Alkaloids found in these plants include

chaconine α-Chaconine is a steroidal glycoalkaloid that occurs in plants of the family Solanaceae. It is a natural toxicant produced in green potatoes and gives the potato a bitter taste. Tubers produce this glycoalkaloid in response to stress, providing ...

solanine Solanine is a glycoalkaloid poison found in species of the nightshade family within the genus ''Solanum'', such as the potato (''Solanum tuberosum''), the tomato (''Solanum lycopersicum''), and the eggplant (''Solanum melongena''). It can occu ...

, solasodine, tomatidine,

tomatine Tomatine (sometimes called tomatin or lycopersicin) is a glycoalkaloid, found in the stems and leaves of tomato plants, and in the fruits at much lower concentrations. Chemically pure tomatine is a white crystalline solid at standard temperature ...

, and

solanidine Solanidine is a poisonous steroidal alkaloid chemical compound that occurs in plants of the family Solanaceae, such as potato and ''Solanum americanum''. Human ingestion of solanidine also occurs via the consumption of the glycoalkaloids, α-solan ...

. The Itkin group has found several of the

biosynthetic gene cluster Metabolic gene clusters or biosynthetic gene clusters are tightly linked sets of mostly non-homologous genes participating in a common, discrete metabolic pathway. The genes are in physical vicinity to each other on the genome, and their expression ...

s for these. In Itkin ''et al.'' 2011 and Itkin ''et al.'' 2013 they find several BSGs for α-tomatine in tomato and

α-solanine Solanine is a glycoalkaloid poison found in species of the Solanaceae, nightshade family within the genus ''Solanum'', such as the potato (''Solanum tuberosum''), the tomato (''Solanum lycopersicum''), and the eggplant (''Solanum melongena''). ...

in potato. Typically they are used in plants as a protection mechanism against animals. Due to the typical anti- cholinesterase activity, they can be used as poisons against the plants' predators. They can be used as starting materials for steroidal drugs. There are various tests for identifying these alkaloids. The characteristic test involves dissolving the compound in hot amyl alcohol or ethanol and watching for the formation of a jelly-like product as the mixture cools.

Veratrum alkaloids

True to their name, Veratrum alkaloids come from plants of the genus ''Veratrum''. Alkaloids are found in the roots and

rhizome In botany and dendrology, a rhizome (; , ) is a modified subterranean plant stem that sends out roots and shoots from its nodes. Rhizomes are also called creeping rootstalks or just rootstalks. Rhizomes develop from axillary buds and grow hori ...

s of these plants. They include

veratridine Veratridine is a steroidal alkaloid found in plants of the lily family, specifically the genera ''Veratrum'' and ''Schoenocaulon''. Upon absorption through the skin or mucous membranes, it acts as a neurotoxin by binding to and preventing the inac ...

cyclopamine Cyclopamine (11-deoxojervine) is a naturally occurring chemical that belongs in the family of steroidal alkaloids. It is a teratogen isolated from the corn lily (''Veratrum californicum'') that causes fatal birth defects. It prevents the embryon ...

, and

jervine Jervine is a steroidal alkaloid with molecular formula C27H39NO3 which is derived from the plant genus ''Veratrum''. Similar to cyclopamine, which also occurs in the genus ''Veratrum'', it is a teratogen implicated in birth defects when consumed ...

. Because of their actions on the cardiovascular, neuromuscular, and respiratory systems, Veratrum alkaloids have been used for the treatment of various conditions like

myasthenia gravis Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, dro ...

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...

, and eclampsia.

Bioactivity

Steroidal alkaloids have been investigated for a wide range of potential bioactivities including antimicrobial, anti-inflammatory,

anti-estrogenic Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor (ER) and/or inh ...

, and

chemotherapeutic Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

activity. These bioactivities are the result of a wide array of mechanisms across different compounds. For example, solasodine antimicrobial bioactivity is accomplished by interfering with the synthesis of genetic substances in ''

Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...

'' and ''

Prototheca wickerhamii ''Prototheca wickerhamii'' is a ubiquitous green alga that does not have chlorophyll. It is widely present in the environment but is a rare cause of infection in humans (protothecosis) and most commonly presents as nodules of the skin. Most ca ...

''. Solasodine inhibits growth signaling in ''Geim original algal''. On the other hand, tomatidine synergistically works with aminoglycosides as antibiotics against '' S. aureus''. Antiinflammation is similarly accomplished with a variety of mechanisms. Solasodine, for example, reduces interleukin-2 and -8 production whereas tomatidine inhibits specific nuclear translocation,

JNK c-Jun N-terminal kinases (JNKs), were originally identified as kinases that bind and phosphorylate c-Jun on Ser-63 and Ser-73 within its transcriptional activation domain. They belong to the mitogen-activated protein kinase family, and are ...

activation, as well as induce

nitrous oxide Nitrous oxide (dinitrogen oxide or dinitrogen monoxide), commonly known as laughing gas, nitrous, or nos, is a chemical compound, an oxide of nitrogen with the formula . At room temperature, it is a colourless non-flammable gas, and has a ...

synthase. Lastly, nine steroidal alkaloids have significant antiestrogenic activity whereas seven inhibit estrone sulfatase. However, in addition to their therapeutic benefits, steroidal alkaloids, specifically veratrum alkaloids, are potentially deadly. Veratrum alkaloid compounds act by attaching to voltage-gated sodium ion channels, altering their permeability. Veratrum alkaloids cause affected sodium channels to reactivate 1000x slower than unaffected channels. Furthermore, veratrum alkaloids block inactivation of sodium channels and lower their activation threshold so they remain open even at resting potential. As a result, sodium concentrations within the cell rise, leading to increased nerve and muscle excitability. These biochemical channels cause muscle contractions, repetitive firing of the nerves and an irregular heart rhythm caused by stimulation of vagal nerves which control the parasympathetic functions of the heart, lungs and digestive tract.

References

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