Distribution and Importance of Phyllanthus Species
Phyllanthus is a large and complex genus in the Euphorbiaceae, currently thought to contain between 550 and 750 species in 11 subgenera. While most commonly found in the tropics, species occur from tropical to mildly temperate zones on all continents except Europe and Antarctica. Some weedy species have become dispersed throughout most of the tropics, but many others are fairly restricted in known range. Two fruit-bearing trees, P. acidus L. and P. emblica L., have been minor items of commerce for centuries. Some species have widely dispersed records of medicinal use, but generally the plants so used have not been cultivated.
Webster, who is working on a global revision of the genus, believes the subgenera fall into the evolutionary affinity groupings of: (a) Isocladus; (b) Kirganelia-Cicca-Emblica; (c) Phyllanthus; (d) Conami-Gomphidium-Phyllanthodendron; (e) Xylophylla-Botryanthus; and (f) Eriococcus. Species of the subgenera Eriococcus and Phyllanthodendron are known only from Asia. Species of the affinity grouping Xylophylla-Botryanthus are known only from the Americas, including the West Indies. The remaining affinity groups all include species indigenous to the Americas, Africa, Asia, and Oceania, although members of Cicca are believed to be strictly New World and members of Emblica strictly Old World. Species pertaining to Isocladus, Phyllanthus, and some species of Kirganelia are generally encountered as herbs; species of the other subgenera are generally shrubs or trees.
Like many members of the Euphorbiaceae, Phyllanthus contains compounds known to be biologically active. Reports of biological activity have tended to follow subgeneric taxonomy, as ellaborated in Unander et al.. Multiple reports of toxicity have been associated with some sections of Isocladus and of Kirganelia, for example, whereas species in other sections are associated with panacea-type folk usage. The fruits of P. acidus (subgenus Cicca) and P. emblica (subgenus Emblica) have been consumed or applied for many types of internal and external complaints. Medicinal use of fruits of P. emblica can be documented to the 9th century (Al-Kindi 850).
The herbaceous species of subgenus Phyllanthus are the most widely used medicinal plants in this genus. The list of diseases treated with some of them suggests perception in some cultures as a panacea, similar to some of the species in subgenus Isocladus. Applications have included external uses, such as poultices to treat wounds, and internal, such as decoctions to treat fevers, pain, jaundice, etc.. Recent interest in possible antiviral effects has focused on the subgenus Phyllanthus, particularly the species P. amarus Schum. & Thonn. and P. urinaria L.
The trees of subgenus Conami have been traditionally used as fish poisons, and antineoplastic compounds have been characterized from the roots. The subgenera Gomphidium, Phyllanthodendron and Botryanthus have few or no reports of ethnobotanical usage or biological activity. There are slightly more references for members of the subgenera Eriococcus and Xylophyllus, but data are still scarce to develop themes of usage or possible effect.
Caution is needed regarding synonyms and taxonomic errors in this large genus. Unander et al. attempted to clarify known synonyms and errors for Phyllanthus species with records of medicinal use for future workers. One very common error is to reference P. niruri L., when P. amarus, P. debilis Klein ex Willd. or P.fraternus Webster is intended. There are numerous citations of similar, but different plants in Africa and Asia under the name P. niruri. The herbarium type of P. niruri was collected in Barbados, West Indies (Linnaeus 1738), and true P. niruri has never been confirmed outside the Americas. This particular issue is further discussed in Webster and Unander.
Conventional Practices for Propagation, and Production of Medicinal Compounds
With the exceptions of P. acidus and P. emblica, Phyllanthus species have generally been collected from wild stands rather than being cultivated. Propagation and culture recommendations for P. acidus and P. emblica are similar to many tropical fruit trees; nothing unusual is required, and they can be propagated by seeds or by several types of cuttings. In southern China, recommendations for cultivation of the herb P. urinaria include warm, well-drained, sandy soil, well-fertilized with N and K (Kangsu Medical Institute 1975). Data from herbarium sheets, personal observations, and the taxonomic literature all suggest a habitat preference for calcareous sites in humid tropical areas by the herbaceous subgenus Phyllanthus ().
Unander et al. tested methods of cultivation for production of both good yields of P. amarus and inhibition of the viral DNA polymerase (DNAp) of hepadnaviruses, (the hepatitis B virus group), equivalent to that in plants collected from the wild. This species grew slowly, and was a poor competitor with aggressive weeds. Maximum size and vigor was reached between 5 and 7 months after sowing; after that time, additional growth seemed limited, and plants gradually senesced or succumbed to disease. Best results were obtained using a plastic mulch to control weeds and additional fertilization supplied by trickle irrigation. Under south Florida conditions, in a field of crushed limestone soil, the highest yields (30-50 g/plant, dry weight), occurred following sowing in the winter dry season and harvesting in mid-summer before the arrival of heavy rains. Cultivated plants in south Florida had inhibition of viral DNAp equivalent to plants from the wild in India or Puerto Rico. Different levels of fertilization had only small effects on the level of DNAp inhibition by aqueous extracts. Extracts of P. amarus prepared from plants of many different sizes, or from shoots and roots gave similar inhibition of the viral DNAp of hepadnaviruses (Unander et al. 1993). This suggested that the active compound(s) was generally present, and hence also obtainable from a callus culture.
Seeds of P. amarus require light to germinate. Six-month old seeds of P. amarus were sown in Petri plates containing filter paper and a cellulose gel. Plates were either wrapped completely in aluminum foil or unwrapped and kept under continuous light in a growth chamber. Replicated treatments were given 0, 40, 160, or 480 h of light. An additional set of replicates was kept in continuous dark for 6 weeks (1008 h). Seeds kept continuously in the dark showed no germination. The regression of percent germination on the hours of light exposure was highly significant. For 40, 160, and 480 h of light exposure, the average germination percentages were 0.3%±0.66, 11.3%+4.7 and 33.3% ± 14.5, respectively. For cultivation, the best stands with the small seeds of P. amarus (approx. 0.15 mg each) were obtained by sowing seeds in a shallow medium on top of the soil or by using transplants with seeds similarly sown in small pots.
Ishimaru et al. successfully grew P. niruri hydroponically, although the details are not given in their paper. Leaves and stems of these plants contained hydrolyzable tannins similar to the plants collected from the wild in Peru.
There are perhaps three groups of Phyllanthus species that have been the focus of attention; these are briefly considered here.
The fruits of P. acidus and P. emblica are widely used as folk remedies for a variety of ailments, mostly internal, and the preferred form is generally some sort of preparation of the fruit pulp. A variety of research reports support some type of biological activity. A single tree of either species is capable of producing impressive quantities of fruit. No shortage seems to exist for the current market, and if there were, it would be most economically filled by additional trees.
For the herbaceous species of the subgenus Phyllanthus, the demand for use in traditional medicine seems currently to be met by collection from the wild or from relatively simple cultivation schemes. The plants that are widely used from this subgenus are all common colonizers of disturbed sites in the tropics, especially calcareous locations, including cracks in concrete. Hence, none of them seems endangered by harvesting at the current level.
Although there has been considerable interest in possible antiviral effects against hepatitis B or retro viruses, consistent positive results in vivo have not yet been shown. In vitro effects exist in a number of the species in the subgenera Isocladus and Phyllanthus, (), but it is not yet clear what these results mean in vivo. Reports of antiviral effects in animal or human trials with hepadnaviruses have so far not been repeatable. Other avenues of research in the subgenus Phyllanthus have been less explored. There has been, for example, little experimentation with effects on other virus families.
The herbs of the subgenus Phyllanthus have been as widely used as folk medicines to treat malaria as they have to treat any viral diseases, but have likewise so far demonstrated no consistent effects in vivo against Plasmodium spp.. We hypothesized the existence of an analgesic effect as a possible explanation of the wide usage. Some recent results support the presence of analgesic compounds, possibly with novel properties.
The third group of plants are the trees of the subgenus Conami which possess a number of novel antineoplastic compounds. These are currently being evaluated in clinical trials. If results continue to be positive, these plants seem one of the best targets for tissue culture production and extraction of active components. At present, all material is being obtained from roots of trees growing in Central America.
Although much less well studied, there are also a number of other interesting leads for drug research that are being pursued among the 550+ other species. If successful, any of these might also create a need for a tissue culture production system for a purified active ingredient.
Phyllanthus Species: Summary
No difficulty was encountered in successful tissue culture of several species of Phyllanthus. Extracts of in vitro culture and of whole plants are abundant in hydrolyzable tannins, some of which demonstrate biological activity which may be of medical interest. This large genus, typical of the family Euphorbiaceae, contains many secondary metabolites, but in vitro production of nontannin components has not been pursued to date.
Although there are many records of medicinal use for members of this genus, good data to confirm or disprove these uses are often lacking. In the case of trees of the subgenus Conami, traditional use as a fish poison might be related to putative antineoplastic glycosides isolated from the roots. One of these compounds has shown sufficient promise to advance to clinical trials. The supply, however, still depends on extraction from whole roots from P. acuminatus, and this seems to be the best current candidate for developing a system of secondary metabolite production in vitro.
Selections from the book: “Medicinal and Aromatic Plants IX” (1996).