Description, Distribution, and Uses of Heimia salicifolia
Heimia salicifolia, a small shrub of the Lythraceae is the source of biphenylquinolizidine lactones and related alkaloids. Heimia is distributed throughout the tropical and subtropical climates of the American Continent and has been described as reaching 0.5-3 m in height. It has sessile, linear lanceolate leaves that are generally opposite. The yellow flowers are solitary and axillary. The fruit is a capsule filled with small (ca. 0.5 mm diameter) ovoid seeds.
H. salicifolia has received several common names. In Mexico it is mostly known as sinicuiche and less frequently as sinicuilche, sinicuil, huachinol, anchinol and xonecuili. In Brazil it is locally known as abre-o-sol, herva da vida and quebra arado and in Argentina as quiebra arado. The Mexican name sinicuiche is of most common use.
H. salicifolia has been used as a folk remedy especially in Mexico. It has been employed as a diuretic, laxative, antisyphilitic, emetic, vulnerary, digestive and to treat cases of dysentery, inflammation of the uterus, bronchitis, and other chest ailments. In addition, inhibition of a beverage produced from the fermented plant is said to cause a mild state of intoxication with visual, auditory, and time perception disorders.
The major alkaloids vertine (cryogenine) (7) and nesodine (6) have been shown to possess significant oral anti-inflammatory activity and this action may explain several of the reported uses of H. salicifolia as a folk remedy. The alkaloids are not yet marketed as therapeutic agents.
Products of Secondary Metabolism
Alkaloids. H. salicifolia is a good source of biphenylquinolizidine lactones. This class of family-specific alkaloids has to this date been relatively rare – only five additional species have produced it. Whereas vertine (7) and lyfoline (7) are the major compounds, the biphenyl-quinolizidines sinicuichine (2), heimidine (4), lythrine (5), nesodine (6), dehydrodecodine (8) and lythridine (9) accumulate in the field-grown plants, and in much larger amounts than the biogenetically simpler phenylquinolizidinyl esters abresoline (75), demethoxyabresoline (14) and its H-10 epimer (77). The phenyl-quinolizidinols demethyllasubine-I (70) and -II (12) are only metabolites of young (5- to 10-day-old) plantlets.
Non-Nitrogenous Compounds. The triterpenes ursolic acid and sitosterol as well as ellagic acid and mannitol have been isolated, but non-alkaloidal compounds of less universal occurrence have not yet been shown to occur in Heimia.
H. salicifolia produces numerous seeds that readily germinate in moisture and light. The plants grow easily in humid areas. Thus, special precautions are probably not necessary for its propagation in the tropical regions where it is indigenous.
In our laboratory, the plant is propagated from seeds. Plantlets are first developed for 6 to 10 months in the greenhouse and plotted in the field in June. In late August or September the aboveground parts are collected for alkaloid isolation. Some plants are left in the field to yield seeds that are harvested in late October; the residual plant may be taken into the greenhouse and replotted in the following spring. A good yield of alkaloids can be obtained from 16- to 18-month-old plants, which implies a 2-year growth period.
The majority of the pharmacologic investigations on H. salicifolia and its alkaloids were carried out in the laboratory of M. H. Malone. The studies dealt principally with the major biphenylquinolizidine lactone vertine (7) (cryogenine), and this subject has been recently reviewed. This has partially been summarized below. Cryogenine (vertine) possesses oral anti-inflammatory activity in several pharmacologic systems. It has been shown to reduce carrageenan-in-duced pedal edema and to modify adjuvant-induced polyarthritis in rats, being equivalent to phenylbutazone in both models. The alkaloid was shown to be less effective than phenylbutazone in modifying cotton pellet-induced granuloma formation in the rat. Vertine (7) also showed significant anti-inflammatory activity in histamine-induced intradermal wheal formation in rabbits, thermal-induced hind-leg edema in rats, serotonin-induced pedal edema in rats and croton oil-induced ear edema in mice. Cryogenine (vertine) was shown to cause hyperglycemia in normal rats and it also elevated alloxan-induced hyperglycemia.
Passivity was the most prominent symptom upon parenteral administration. Intraperitoneally administered cryogenine (vertine) selectively blocked discrete conditioned avoidance responding (25 mg 1 being equivalent to 2 mg chlorpromazine in this test), but was shown to be less effective in blocking continuous conditioned avoidance responding. Additional pharmacological, as well as toxicity studies, have been reviewed by Malone.
Prostaglandin synthetase inhibition studies were recently carried out by Lema et al. (1986). It was shown that cryogenine (vertine) (7) and nesodine (6) were respectively 2.48 and 2.24 times as active as aspirin as inhibitors of prostaglandin synthetase isolated from bovine seminal vesicles (phenylbutazone and indomethacin were respectively 2800 and 8.75 times as potent inhibitors). This enzyme-inhibitory effect may explain much of the anti-inflammatory activity of the alkaloids.
Heimia salicifolia: Conclusions
Shoot culture of Heimia salicifolia is a reliable system for the in vitro production of both biphenylquinolizidine lactones and phenylquinolizidines. The metabolic activity of the culture – as it relates to alkaloid synthesis and accumulation – is a combination of the activities expressed by young seedlings and older field-grown plants. However, not all the alkaloids produced by the mature plants accumulate in the multiple shoots.
The reproducibility of the alkaloid production by the biological system delineated in this review reinforces the conclusions that shoot organ cultures offer a possible alternative to cell cultures, for the in vitro production of secondary plant products.
Selections from the book: “Medicinal and Aromatic Plants II”, 1989.