Antiprotozoal and antihelminthic properties of plants ingested by wild Japanese macaques (Macaca fuscata yakui) in Yakushima Island.

ETHNOPHARMACOLOGICAL RELEVANCE: Primates forage on a variety of plant parts to balance their dietary intake to meet requirements of energy, nutrition and maintenance, however the reason(s) leading them to ingest some plants which have no nutritional value and/or contain bioactive or even toxic secondary metabolites is recently gaining closer attention. The growing literature suggests that primates consume plants for medicinal purposes (self-medication) as well, particularly when infected with parasites and pathogens (bacteria, viruses, microbes). Interestingly, some of the plants they consume are also used by humans for similar purposes or may have potential uses for humans. MATERIALS AND METHODS: As part of a 16-month study of the parasite ecology of a sub-species of Japanese macaques (Macaca fuscata yakui) on the island of Yakushima, we surveyed their feeding habits and collected a subset of plants and plant parts observed being ingested by macaques. The ethnomedicinal value of these plants was surveyed and methanolic extracts of 45 plant parts were tested in vitro against important parasites of humans, including four protozoan parasites Plasmodium falciparum, Trypanosoma brucei rhodesiense, T. cruzi and Leishmania donovani, and the trematode flatworm Schistosoma mansoni. Potential toxicity of the extracts was also assessed on mammalian cells. RESULTS: A wide range of ethnomedicinal uses in Asia for these plants is noted, with 37% associated with the treatment of parasites, pathogens and related symptoms. Additionally, the 45 extracts tested showed broad and significant activity against our test organisms. All extracts were active against T. b. rhodesiense. The majority (over 80%) inhibited the growth of P. falciparum and L. donovani. Half of the extracts also displayed antiprotozoal potential against T. cruzi while only several extracts were active against both larval and adult stages of S. mansoni. Cytotoxicity was generally low, although several extracts lacked specific toxicity to test parasites. CONCLUSIONS: Our results indicated a number of plants and their parts to have antiparasitic activity not previously reported in the ethnopharmacological literature. Enhanced understanding of the primate diets, particularly during periods of intensified parasite infection risk may help to further narrow down plants of interest for lead compound development. The study of animal self-medication is a complementary approach, with precedence, to drug discovery of new lead drug compounds against human parasitic diseases.

Paleomedicine and the use of plant secondary compounds in the Paleolithic and Early Neolithic.

Reconstructing plant use before domestication is challenging due to a lack of evidence. Yet, on the small number of sites with assemblages, the wide range of different plant species cannot be explained simply in terms of nutrition. Assemblages from the Lower Paleolithic to the Early Neolithic were examined to investigate the relative edible and medicinal properties of the plants. The assemblages contain a mixture of edible species, plants that are both edible and medicinal, and plants with only medicinal properties. The proportion of medicinal plants at all sites is well above the natural average and increases over time. Mechanisms for preventing intestinal parasitic infections are common among animals and together with chimpanzees' preventative and curative self-medication practices suggest an evolutionary context for this behavior. A broad-spectrum approach to plant collection is likely to have been in place throughout the Paleolithic driven, in part, by the need for medicinal compounds.

Relative abilities of young sheep and goats to self-medicate with tannin-rich sainfoin when infected with gastrointestinal nematodes.

Plant secondary metabolites (PSM) are one of the promising options to control gastrointestinal nematodes in sheep and goats. The objective of this study was to assess the abilities of sheep and goats to self-medicate with tannin-rich sainfoin (Onobrychis viciifolia) (SF) when infected with gastrointestinal nematodes, using a cafeteria and an operant conditioning trial. Hypotheses were that parasitized (P) lambs and goat kids would show greater intake and preference for SF than their non-parasitized (NP) counterparts, that kids would eat more SF than lambs (due to their lower resistance against parasites and their greater ability to consume PSM), and that SF intake would increase over time for P animals. We used 20 female kids and 20 ewe lambs aged 3 months. Half of the animals per species (n = 10) were experimentally infected with 170 L3 larvae of Haemonchus contortus/kg of BW (P). The other half were free from parasites throughout the study (NP). Five weeks after infection, animals were exposed to a 24-day cafeteria trial (three 8-day periods) offering a free choice between two legume pellets: SF (3.8% condensed tannins) and alfalfa (ALF, Medicago sativa; no tannin). Subsequently, animals were involved in an operant conditioning trial of two 4-day long sessions, to assess in short-term tests their motivation to walk for a SF reward when offered in choice with freely available ALF. In the cafeteria trial, SF preference was greater in kids than in lambs, particularly in the first two periods. We did not observe a greater preference for SF in P animals, which was even greater in NP animals for periods 1 and 2. Sainfoin intake increased through periods for P animals, which led to similar SF preferences for all groups during period 3. In the operant-conditioning trial, motivation to get the SF reward was similar between P and NP animals. These results support the hypotheses that goats are more willing to consume tanniferous feeds than sheep, and that P animals increased SF intake through time. However, the emergence of a curative self-medicative behaviour was not supported, as P individuals did not show greater SF intake, preference, nor a greater motivation to get SF than NP animals, regardless of animal species. These findings are discussed with previous results and some explanations are presented.

Potential self-medication using millipede secretions in red-fronted lemurs: combining anointment and ingestion for a joint action against gastrointestinal parasites?

Self-anointing, referring to the behaviour of rubbing a material object or foreign substance over different parts of the body, has been observed in several vertebrate species, including primates. Several functions, such as detoxifying a rich food source, social communication and protection against ectoparasites, have been proposed to explain this behaviour. Here, we report observations of six wild red-fronted lemurs (Eulemur rufifrons) of both sexes and different age classes anointing their perianal-genital areas and tails with chewed millipedes. Several individuals also ingested millipedes after prolonged chewing. In light of the features of the observed interactions with millipedes, and the nature and potential metabolic pathways of the released chemicals, we suggest a potential self-medicative function. Specifically, we propose that anointing combined with the ingestion of millipedes' benzoquinone secretions by red-fronted lemurs may act in a complementary fashion against gastrointestinal parasite infections, and more specifically Oxyuridae nematodes, providing both prophylactic and therapeutic effects.

Ruminant self-medication against gastrointestinal nematodes: evidence, mechanism, and origins.

Gastrointestinal helminths challenge ruminants in ways that reduce their fitness. In turn, ruminants have evolved physiological and behavioral adaptations that counteract this challenge. Ruminants display anorexia and avoidance behaviors, which tend to reduce the incidence of parasitism. In addition, ruminants appear to learn to self-medicate against gastrointestinal parasites by increasing consumption of plant secondary compounds with antiparasitic actions. This selective feeding improves health and fitness. Here, we review the evidence for self-medication in ruminants, propose a hypothesis to explain self-medicative behaviors (based on post-ingestive consequences), and discuss mechanisms (e.g., enhanced neophilia, social transmission) that may underlie the ontogeny and spread of self-medicative behaviors in social groups. A better understanding of the mechanisms that underlie and trigger self-medication in parasitized animals will help scientists devise innovative and more sustainable management strategies for improving ruminant health and well-being.

New evidence for self-medication in bonobos: Manniophyton fulvum leaf- and stemstrip-swallowing from LuiKotale, Salonga National Park, DR Congo.

The swallowing of entire leaves by apes across Africa without chewing has been observed for over 40 plant species. Here we add evidence for (a) a new site, LuiKotale where leaf-swallowing of Manniophyton fulvum (Euphorbiaceae) is observed in bonobos, (b) a so far unreported ingestion of unchewed stemstrips of M. fulvum, we name stemstrip-swallowing; and (c) a test of some of the requirements put forward by Huffman for the assessment of plants ingested for medical purpose. As ecological correlates we analyzed M. fulvum phenological data and examined 1,094 dung piles collected between 2002 and 2009. By that we assessed availability and choice of leaves. In addition, we provide the first full description of the behavior related to this plant species' use by chimpanzees or bonobos using 56 bouts of M. fulvum ingestion observed between October 2007 and February 2010. With these data we tested and met 4 of the 6 requirements given by Huffman, supporting ingestion of this species as self-medication. Despite species' year-round availability and abundance, M. fulvum was ingested only at specific times, in very small amounts, and by a small proportion of individuals per party. In the absence of our own parasitological data, we used M. fulvum swallowing as evidence for parasite infestation, and seasonality as a proxy for stressors underlying seasonal fluctuation and impacting immune responses. Using these indirect factors available, we investigated conditions for a parasite to develop to its infective stage as well as conditions for the host to cope with infections. Both rain and temperature were good predictors for M. fulvum ingestion. We discuss the use of M. fulvum with respect to its hispidity and subsequent purging properties and provide insight into its ethnomedicinal uses by humans, stimulating speculations about potentially additional pharmacological effects.

High frequency of leaf swallowing and its relationship to intestinal parasite expulsion in "village" chimpanzees at Bulindi, Uganda.

Self-medication by great apes to control intestinal parasite infections has been documented at sites across Africa. Chimpanzees (Pan troglodytes) swallow the leaves of certain plant species whole, without chewing. Previous studies demonstrated a relationship between chimpanzee leaf swallowing and expulsion of nematode worms (Oesophagostomum sp.) and tapeworms (Bertiella sp.) in dung. We investigated the relationship between leaf swallowing and parasite expulsion in chimpanzees inhabiting a fragmented forest-farm mosaic at Bulindi, Uganda. During 13 months whole undigested leaves occurred in chimpanzee dung at a considerably higher frequency (10.4% of dungs) than at other sites (0.4-4.0%). Leaf swallowing occurred year-round and showed no pronounced seasonality. Chimpanzees egested adults of multiple species of Oesophagostomum (including O. stephanostomum) and proglottids of two tapeworms-Bertiella sp. and probably Raillietina sp. The latter may not be a true infection, but the byproduct of predation on domestic fowl. Compared to previous studies, the co-occurrence of whole leaves and parasites in chimpanzee dung was low. Whereas the presence of leaves in dung increased the probability of adult nematode expulsion, no association between leaf swallowing and the shedding of tapeworm proglottids was apparent. Anthropogenic habitat changes have been linked to alterations in host-parasite interactions. At Bulindi, deforestation for agriculture has increased contact between apes and people. Elevated levels of leaf swallowing could indicate these chimpanzees are especially vulnerable to parasite infections, possibly due to environmental changes and/or increased stress levels arising from a high frequency of contact with humans. Frequent self-medication by chimpanzees in a high-risk environment could be a generalized adaptation to multiple parasite infections that respond differently to the behavior. Future parasitological surveys of apes and humans at Bulindi are needed for chimpanzee health monitoring and management, and to investigate the potential for disease transmission among apes, people, and domestic animals.

A self-medicating applicator for control of ticks on deer.

A self-medicating applicator for killing ticks on deer and domestic ungulates by passive transfer of acaricides during feeding is described. The applicator consists of a barrel divided into a food bin (above) and a sealed self-contained acaricide reservoir (below) with a vertical, centrally-located ceramic column that extends from the reservoir into the food bin. Acaricide is drawn up the column from the sealed reservoir by absorption. Animals attracted to the food in the device acquire the acaricide during feeding when they contact the uppermost portion of the column. White-tailed deer (Odocoileus virginianus) readily utilize the applicator in penned and natural conditions. In a field study, examination of hunter-killed deer demonstrated that animals from a treated site were infested with many fewer Ixodes scapularis (3.4 +/- 1.1) than those from a control site (10.8 +/- 3.0). Chromatographic analysis of hair samples revealed traces of permethrin on three of the four animals examined, suggesting use of applicators by these deer. In a study using penned goats (Capra hircus) infested with Amblyomma americanum ticks, treatment efficacy reached 86.4% within 4 days of exposure to the applicators. Visual observations confirmed that all animals used the applicators. Gas chromatographic analysis of goat hair samples indicated that permethrin was detectable on all of the treated animals exposed to the device.