Names | |
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IUPAC name (1S,11R,13S,14S,24R,26S)-13,26-Dimethyl-2,15-dioxa- | |
Other names (+)-Carpaine | |
Identifiers | |
3D model (JSmol) | |
ChEBI | |
ChemSpider | |
ECHA InfoCard | 100.020.378 |
PubChem CID | |
UNII | |
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Properties | |
C28H50N2O4 | |
Molar mass | 478.70 g/mol |
Melting point | 121 °C |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Carpaine is one of the major alkaloid components of papaya leaves which has been studied for its cardiovascular effects. [2] Carpaine extracted from Carica papaya trees has been reported to have diverse biological properties, such as anti-malarial, anti-inflammatory, anti-oxidant, and vasodilatory effects. [3] Especially, Carpaine possessed significant anti-plasmodial activity in vitro (IC50 of 0.2 μM) and high selectivity towards the parasites. [4]
Circulatory effects of carpaine were studied in Wistar male rats weighing 314 +/- 13 g, under pentobarbital (30 mg/kg) anesthesia. [5] Increasing dosages of carpaine from 0.5 mg/kg to 2.0 mg/kg resulted in progressive decrease in systolic, diastolic, and mean arterial blood pressure. Selective autonomic nervous blockade with atropine sulfate (1 mg/kg) or propranolol hydrochloride (8 mg/kg) did not alter the circulatory response to carpaine. Carpaine, 2 mg/kg, reduced cardiac output, stroke volume, stroke work, and cardiac power, but the calculated total peripheral resistance remained unchanged. It is concluded from these results that carpaine affects the myocardium directly. The effects of carpaine may be related to its macrocyclic dilactone structure, a possible cation chelating structure.
After the first isolation of Carpaine by Greshoff in 1890, Merck & Company assigned the empirical formula C14H27NO2 to it, which was soon corrected to C14H25NO2 by van Rijn. [2] In 1930s, Barger and his collogues investigated various degradation products of Carpaine and was able to obtain a series of chemical structures of Carpaine. [6]
Then in 1953, Rapoport and his collogues at the University of California obtained a new form of Carpaine chemical structure which they found the nitrogen-containing ring had a piperidine structure instead of the pyrrolidine as previously thought; they also located the position of the lactone ring between atoms numbered 3 and 6 on the piperidine nucleus. Later work from Govindachari & Narasimhan and Tichy and Sicher further confirmed this structural formula. [2]
However, Spiteller-Friedmann and Spiteller used Mass Spectrometry to discover that the molecular weight of Carpaine is closer to 478 g/mol, which is represented by twice of the original empirical formula. [2] The new finding proved that Carpaine consists of two identical halves, which form a 26-membered cyclic diester, or dilactone, with an empirical formula of C28H50N2O4, and the configuration was finally determined by Coke and Rice in 1965. [2]
Carpaine occurs in papaya leaves in concentrations as high as 0.4%, which is enough to make it available commercially at very reasonable costs. [2]
One possible extraction route was accomplished first drying the leaves in an electric blast drying oven and milled to fine powder. The powdered plant material were macerated with a mixed solution of ethanol/water/ HCl for 24 hrs at room temperature. Then the extract was dissolved in water/HCl mixture, filtered, and extracted with petroleum ether to remove fat materials. The acid fraction was adjusted to pH 8.0 ~ 9.0 using NH4OH solution and extracted with chloroform. Finally, the chloroform fractions were pooled and evaporated and the whole operation was repeated again so the crude alkaloid Carpaine was obtained. [7]
Another extraction route reported that mechanical blending of the leaves prior to extraction significantly enhances the yield of Carpaine. After blending the leaves with water and freeze-dried, the samples were soaked in ethanol. This mixture was then concentrated and purified using an acid-base method followed by chloroform extraction to isolate the Carpaine. Finally, the purity and structure were analyzed using NMR and LC-MS. [8]
Recent research highlights the possible efficacy of Carpaine in managing the symptoms and severe complications associated with dengue fever. Carpaine in papaya leaves extract is the major active compounds that contributes to the anti-thrombocytopenic activity (raising the platelet counts in patient's blood). For example, a treatment used for a 45-year-old male patient in Pakistan diagonosed with dengue fever involved administering 25mL of the extracted Carpaine twice daily for five consecutive days. The treatment showed significant improvement in hematological parameters, a substantial increase in platelet and blood cell counts and neutrophil levels. [8]
In the setting of ischemia-reperfusion injury (IRI), studies have shown Carpaine provided significant protection to recover the wounded area affected by the hydrogen peroxide treatment by activating key pathway that promotes cell cycle progression and prevents cell death during stressful condition. Furthermore, Carpaine treatment further demonstrates its cardioprotective effects by improving mitochondrial membrane potential and reducing the overproduction of reactive oxygen species. [9]
Studies have shown Carpaine’s ability to modulate the body’s inflammatory response by inhibiting the production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which would be beneficial in treating chronic disease, including rheumatoid arthritis, asthma, etc. [10]
The enhanced anti-oxidant activity in papaya leaves demonstrated in studies is due to the high concentration of polyphenols, which are known for their strong anti-oxidant properties for combatting oxidative stress in the body, that can lead to cellular damage and various chronic diseases. The anti-oxidant capacity was measured using the DPPH (1,1-diphenyl-2-picrylhydrazyl) assay, where blended young papaya leaves exhibited significantly lower IC50 values (IC50 = 293 μg/mL per 100 mg) with a stronger anti-oxidant potency than old leaves (IC50 = 382 μg/mL per 100 mg). [8]
Aconitine is an alkaloid toxin produced by various plant species belonging to the genus Aconitum, commonly known by the names wolfsbane and monkshood. Aconitine is notorious for its toxic properties.
Solanine is a glycoalkaloid poison found in species of the nightshade family within the genus Solanum, such as the potato, the tomato, and the eggplant. It can occur naturally in any part of the plant, including the leaves, fruit, and tubers. Solanine has pesticidal properties, and it is one of the plant's natural defenses. Solanine was first isolated in 1820 from the berries of the European black nightshade, after which it was named. It belongs to the chemical family of saponins.
Hyperforin is a phytochemical produced by some of the members of the plant genus Hypericum, notably Hypericum perforatum. Hyperforin may be involved in the pharmacological effects of St. John's wort, specifically in its antidepressant effects.
Synephrine, or, more specifically, p-synephrine, is an alkaloid, occurring naturally in some plants and animals, and also in approved drugs products as its m-substituted analog known as neo-synephrine. p-Synephrine and m-synephrine are known for their longer acting adrenergic effects compared to epinephrine and norepinephrine. This substance is present at very low concentrations in common foodstuffs such as orange juice and other orange products, both of the "sweet" and "bitter" variety. The preparations used in traditional Chinese medicine (TCM), also known as Zhi Shi (枳实), are the immature and dried whole oranges from Citrus aurantium. Extracts of the same material or purified synephrine are also marketed in the US, sometimes in combination with caffeine, as a weight-loss-promoting dietary supplement for oral consumption. While the traditional preparations have been in use for millennia as a component of TCM-formulas, synephrine itself is not an approved over the counter drug. As a pharmaceutical, m-synephrine (phenylephrine) is still used as a sympathomimetic, mostly by injection for the treatment of emergencies such as shock, and rarely orally for the treatment of bronchial problems associated with asthma and hay-fever.
Samandarin or Samandarine is the main steroidal alkaloid secreted by the fire salamander (Salamandra salamandra). The compound is extremely toxic (LD50 = 70 μg/kg in mice). Poisoning can cause convulsions, respiratory paralysis, and eventual death. Samandarin is also believed to be the active ingredient in Salamander brandy, a Slovenian traditional medicinal alcoholic drink with purported hallucinogenic and aphrodisiac effects.
Withania somnifera, known commonly as ashwagandha, is an evergreen shrub in the Solanaceae or nightshade family that grows in India, the Middle East, and parts of Africa. Several other species in the genus Withania are morphologically similar.
Aporphine is an alkaloid with the chemical formula C17H17N. It is the core chemical substructure of the aporphine alkaloids, a subclass of quinoline alkaloids. It can exist in either of two enantiomeric forms, (R)-aporphine and (S)-aporphine.
Methyllycaconitine (MLA) is a diterpenoid alkaloid found in many species of Delphinium (larkspurs). In common with many other diterpenoid alkaloids, it is toxic to animals, although the acute toxicity varies with species. Methyllycaconitine was identified one of the principal toxins in larkspurs responsible for livestock poisoning in the mountain rangelands of North America. Methyllycaconitine has been explored as a possible therapeutic agent for the treatment of spastic paralysis, and it has been shown to have insecticidal properties. It has become an important molecular probe for studying the pharmacology of the nicotinic acetylcholine receptor.
Mesembrine is an alkaloid present in Sceletium tortuosum (kanna). It has been shown to act as a serotonin reuptake inhibitor (Ki = 1.4 nM), and has also been found to behave as a weak inhibitor of the enzyme phosphodiesterase 4 (PDE4) (Ki = 7,800 nM). In an in vitro study published in 2015, researchers concluded that "a high-mesembrine Sceletium extract" may exert anti-depressant effects by acting as a monoamine releasing agent." As such, mesembrine likely plays a dominant role in the antidepressant effects of kanna. The levorotatory isomer, (−)-mesembrine, is the natural form.
Pravadoline (WIN 48,098) is an anti-inflammatory and analgesic drug with an IC50 of 4.9 μM and a Ki of 2511 nM at CB1, related in structure to nonsteroidal anti-inflammatory drugs (NSAIDs) such as indometacin. It was developed in the 1980s as a new antiinflammatory and prostaglandin synthesis inhibitor, acting through inhibition of the enzyme cyclooxygenase (COX).
Delphinine is a toxic diterpenoid alkaloid found in plants from the Delphinium (larkspur) and Atragene genera, both in the family Ranunculaceae. Delphinine is the principal alkaloid found in Delphinium staphisagria seeds – at one time, under the name stavesacre, a very well known herbal treatment for body lice. It is related in structure and has similar effects to aconitine, acting as an allosteric modulator of voltage gated sodium channels, and producing low blood pressure, slowed heart rate and abnormal heart rhythms. These effects make it highly poisonous. While it has been used in some alternative medicines, most of the medical community does not recommend using it due to its extreme toxicity.
Chymopapain is a proteolytic enzyme isolated from the latex of papaya. It is a cysteine protease which belongs to the papain-like protease (PLCP) group. Because of its proteolytic activity, it is the main molecule in the process of chemonucleolysis, used in some procedures like the treatment of herniated lower lumbar discs in the spine by a nonsurgical method.
Ibogamine is an anti-convulsant, anti-addictive, CNS stimulant alkaloid found in Tabernanthe iboga and Crepe Jasmine. Basic research related to how addiction affects the brain has used this chemical.
Nimbin is a triterpenoid isolated from the neem tree. Nimbin is thought to be responsible for much of the biological activities of neem oil, and is reported to have anti-inflammatory, antipyretic, fungicidal, antihistamine and antiseptic properties. The neem tree is found in multiple Asian countries such as China, Thailand, and India. Nimbin is part of the chemical family of limonoids and triterpenoids. Nimbin was first extracted in 1942 from neem seeds by Siddiqi et al. Its molecular formula was established by mass-spectrometry along with salannin, a compound whose chemical formula and properties are very close those of nimbin. Nimbin can be extracted from different parts of the neem tree with a solvent or supercritical carbon dioxide. Nimbin is used for different purposes because it has multiple properties such as insecticide, antiviral, antimicrobial, anti-inflammatory, and anti-fungal. Nimbin was commonly used in traditional Indian and Chinese medicine. For example, it can be used to treat skin conditions like eczema and psoriasis.
Gelsemine (C20H22N2O2) is an indole alkaloid isolated from flowering plants of the genus Gelsemium, a plant native to the subtropical and tropical Americas, and southeast Asia, and is a highly toxic compound that acts as a paralytic, exposure to which can result in death. It has generally potent activity as an agonist of the mammalian glycine receptor, the activation of which leads to an inhibitory postsynaptic potential in neurons following chloride ion influx, and systemically, to muscle relaxation of varying intensity and deleterious effect. Despite its danger and toxicity, recent pharmacological research has suggested that the biological activities of this compound may offer opportunities for developing treatments related to xenobiotic or diet-induced oxidative stress, and of anxiety and other conditions, with ongoing research including attempts to identify safer derivatives and analogs to make use of gelsemine's beneficial effects.
Theacrine, also known as 1,3,7,9-tetramethyluric acid, is a purine alkaloid found in Cupuaçu and in a Chinese tea known as kucha. It shows anti-inflammatory and analgesic effects and appears to affect adenosine signalling in a manner similar to caffeine. In kucha leaves, theacrine is synthesized from caffeine in what is thought to be a three-step pathway. Theacrine and caffeine are structurally similar.
Corydaline is an acetylcholinesterase inhibitor isolated from Corydalis yanhusuo.
Taxine alkaloids, which are often named under the collective title of taxines, are the toxic chemicals that can be isolated from the yew tree. The amount of taxine alkaloids depends on the species of yew, with Taxus baccata and Taxus cuspidata containing the most. The major taxine alkaloids are taxine A and taxine B although there are at least 10 different alkaloids. Until 1956, it was believed that all the taxine alkaloids were one single compound named taxine.
Cyclobuxine is an alkaloid, which can be found in Buxus sempervirens better known as common boxwood, and is derived from the cholesterol skeleton. Alkaloids can be found in the whole plant, but the largest amounts of alkaloids including cyclobuxine can be found in the leaves and bark.
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