Available online 11 March 2015
Some popular medicinal plants and diseases of the Upper Palaeolithic in Western Georgia
Abstract
Ethnopharmacological relevance
Palynological
studies of cultural layers of cave sediments have been used in order to
better understand traditional practices. The Upper Palaeolithic in
Georgia (36,000−11,000 cal. BP) provides a rich source of such material.
However, up to day from such sediments the identification of medicinal
plants has hardly been achieved. Large quantities of pollen most notably
from entomophilous taxa in fossil spectra can serve as a tool to
identify traditionally important species. As these plants are used in
modern popular medicine on the territory of Georgia (like Achillea millefolium L., Artemisia annua L., Artemisia absinthium L., Centaurea jacea L., Urtica dioica
L.) can be served as an indirect evidence for their medicinal relevance
from the Palaeolithic Period up to days. Their modern uses may point
that the main diseases during the Upper Palaeolithic were the same as
today.
Materials and methods
The
Upper Palaeolithic sediments were studied palynologically come from
four caves: Dzudzuana, Satsurblia, Kotias Klde and Bondi. Modern
sediments were investigated from 6 caves. Fossil and modern samples were
taken according to the standard procedure in palynology. The laboratory
treatment was carried out as follows: first, 50 g of the sample was
boiled in 10% KOH. At the second stage, centrifuging of the material in
cadmium liquid was performed. At the final stage, acetolysis treatment
was used.
Results
Pollen of A. absinthium L. (Asteraceae), A. annua L. (Asteraceae), A. millefolium L. (Asteraceae), C. jacea L. (Asteraceae), and U. dioica
L. (Urticaceae) are identified to species level. This species are not
edible and are popular in present-day folk medicine. In the Upper
Palaeolithic layers, significant amounts of studies species pollen were
recorded in the cave, likely due to their flowering branches being
brought in by humans for use. Detailed consideration of the
pharmacological characteristics of the examined species showed that
almost all of them have anti-inflammatory, antibacterial, antimicrobial
and antipyretic activity.
Conclusion
The fossil pollen complex of medicinal herbs, dominated by A. millefolium and Artemisia (A. annua and A. absinthium),
suggests that the ancient population living in the studied caves could
have been prone to malaria, rheumatism and gastrointestinal diseases. In
the Upper Palaeolithic, the population inhabiting cave sites might have
suffered from gout and callouses.
Graphical abstract
Keywords
- Upper Palaeolithic cave;
- Palynology;
- Medicinal plants;
- Paleopharmacology;
- Population diseases
1. Introduction
Palynological
studies of cultural layers of cave sediments make it possible to
reconstruct palaeoecological conditions, due to the transport of large
quantities of plant pollen and spores into the cave (Carrión, 1992, Carrión et al., 1999, Navarro et al., 2000, Navarro et al., 2002, Arobba and Caramiello, 2009, Kvavadze et al., 2011 and Kvavadze et al., 2012). Palynological data are very important for inferring prehistoric uses of medicinal plants (Chaves and Reinhard, 2003). Pollen data have demonstrated that medicinal plants were used by Neanderthals around 60,000 cal. BP (Petrovska, 2012)
and work at the archaeological site of Shanidar IV in present-day Iraq
has shown that Middle Palaeolithic communities used many medicinal
plants (Leroi-Gourhan, 1975 and Lietava, 1992), including Ephedra altissima and Centaurea solstitialis. Achillea, Muscari-type, Althae-type, Senecio-type.
Pollen of medicinal plants has been found in archaeological material from other prehistoric sites worldwide (Merlin, 2003, Chaves and Reinhard, 2003, Eshleman, 2003, Martkopilshvili et al., 2012 and Magyari et al., 2013). Yet there are very few data in the literature regarding the medicines used by Upper Palaeolithic humans (Roberts and Manchester, 1995 and Chaves and Reinhard, 2003).
To solve the problems of palaeopharmacology, caves are the most
suitable object of study since Palaeolithic people used caves as
dwellings and for storage of medicinal remedies.
The
study of modern sediments of caves has shown that they predominantly
contain pollen of anemophilous plants that can easily be transported by
winds over long distances (Burney and Burney, 1993, Navarro et al., 2002 and Eugenia de Porras et al., 2011). As for entomophilous taxa, their role is not very important in recent pollen spectra (Navarro et al., 2000 and Kvavadze et al., 2011).
The
presence of large quantities of entomophilous taxa in fossil spectra is
therefore attributed to direct introduction by humans. Humans may have
brought in edible plants, medicinal herbs, brushwood, branches and wood
to make fire, moss polsters and leaves to cover the cave floor, etc.
In
the foothills of Imereti (western Georgia) the palynological
exploration of cave layers began in the 1980s and 1990s. In Dzudzuana
cave, 19 samples taken from the Upper Palaeolithic layers were studied
by David Lordkipanidze (Meshveliani et al., 1990).
Though the palynological material was not very rich, the researcher
could identify a rather long list of taxa which included pollen of
medicinal plants (Meshveliani et al., 1990). Systematic studies of the Dzudzuana cave started in 2007 (Kvavadze et al., 2009b, Kvavadze et al., 2010a, Meshveliani et al., 2010, Meshveliani et al., 2011 and Bar-Yosef et al., 2011)
and have elevated Dzudzuana cave to a unique site of global
significance since the discovery of twisted and dyed flax and wool
fibres as old as 35,000–30,000 years (Kvavadze et al., 2009b, Kvavadze et al., 2010a and Kvavadze et al., 2011).
These discoveries have significantly changed our understanding of the
activity of Upper Palaeolithic humans, who were not only
hunter-gatherers, but also might have been artisans.
The
objective of the present publication is to investigate the range of
medicinal plants found in the pollen spectra of the Upper Palaeolithic
layers of karst caves in the western part of Georgia and are not edible
and are popular in present-day folk medicine. However, the selection of
taxa was also guided by the possibilities to identify species using
light microscopy. We could unambiguously determine Centaurea jacea L. (Asteraceae), Artemisia annua L. (Asteraceae), Artemisia absinthium L. (Asteraceae), Achillea millefolium L. (Asteraceae), and Urtica dioica L. (Urticaceae), which allowed us to specify their curative properties.
The
main goals of our research are: 1) to consider the pharmacological
properties of medicinal herbs found in the cave sediments and their uses
in modern and traditional medicine; 2) to establish the diseases
typical for the Stone Age population based on modern pharmacological
data for the species identified.
2. Material and methods
2.1. Material, recent environment and palaeoenvironment
The
Upper Palaeolithic sediments we have studied palynologically come from
four caves: Dzudzuana, Satsurblia, Kotias Klde and Bondi. Modern
sediments were investigated from Samertskhle Klde, Khvedelidzeebis,
Datvis, Dzudzuana, Satsrublia and Kotias Klde caves. Fossil and modern
samples were taken according to the standard procedure in palynology (Moore et al., 1991).
The need to study modern sediments inside and outside the cave is
determined by the fact that we do not know how the pollen of different
species is preserved (or not preserved) in the specific conditions (type
of soil, microflora, climate, etc.). It should be noted that medicinal
species such as A. absinthium L., A. millefolium L., C. jacea L and U. dioica
L. grow in the neighbourhood of the caves studied. As ruderal (weedy)
plants they follow human activity, growing in disturbed habitats along
the roads and paths and other trampled places ( Nakhutsrishvili, 2013). Pollen grains of the said medicinal species disperse readily over long distances.
The karst cave Dzudzuana is located near the village Darkveti of the Chiatura municipality at an altitude of 560 m a.s.l. (Fig. 1).
The cave is located in a deep gorge closed in deciduous forest with
predominance of hornbeam and oak. The climate here, as in whole of
Imereti, is warm and humid. The average annual temperature is 13 °C and
the average annual rainfall is 1100–1200 mm (Bondyrev et al., 2014).
- Fig. 1.Map of Georgia (B) and location of investigated sites in the Imereti region (A): 1-Dzudzuana Cave; 2-Satsurblia Cave; 3-Kotias Klde Cave; 4-Bondi Cave; 5-Samerckhle cave; 6-Khvedelidzeebis Cave; 7-Datvis Klde Cave. Triangles indicate studied caves with Upper Palaeolithic layers; circles indicate caves where only modern sediments were investigated. Kutaisi is the capital of Imereti.
In
the cave, 5 profiles were made, from which 86 samples were taken and
investigated palynologically. Each stratigraphic layer was studied and
the absolute age of the whole sequence was defined by 23 radiocarbon
readings (Meshveliani et al., 2006, Meshveliani et al., 2010 and Meshveliani et al., 2011;
Bar Yosef et al. 2011) covering the period from 36,000 to 6000 cal. BP.
The palynological studies have shown that during the formation of the
layer D the climate, on the whole, was cooler than during the formation
of the layer C (Kvavadze et al., 2012).
Unit D (36,000−31,000 cal. BP) represents the early Upper Palaeolithic
Period, which comprises 21 samples. The upper limit of the birch and
pine forest zone was situated near the cave at the time of deposition of
layer D. The climate at this time appears to be cold and dry. Later,
during the formation of layer C, the climate became warm and wet.
Broad-leaved forests of oak, lime, walnut were growing in the vicinity
of the cave. Wignut (Pterocarya pterocarpa), a good indicator
of the warm climate, was growing in the river floodplain. During the
formation of the layer B the climatic conditions became worse (LGM
cooling), and dark coniferous high-mountain forests were spread around
the cave ( Kvavadze et al., 2012).
The Satsurblia karst cave is located in the Tskhaltubo region near the village Kumistavi at an altitude of 360 m a.s.l. (Fig. 1).
Natural vegetation around the cave is almost entirely destroyed and
occupied by crops of corn and other agricultural crops. Climatic
conditions are very similar to those in the vicinity of Dzudzuana cave (Bondyrev et al., 2014).
In this cave, two profiles, as well as the second and the third floor layer dated to the Upper Palaeolithic, were studied (Meshveliani et al., 2013, Kvavadze et al., 2011 and Pinhasi et al., 2014). The floor layers were dated between 17,895−16,215 cal. BP (Pinhasi et al., 2014).
Altogether, 22 samples were investigated from Sarsurblia Cave and six
samples of modern soils and moss were taken inside the cave and at its
entrance. From this material 10 samples, dating of Upper Palaeolithic
Period were chosen here, similar to the Dzudzuana environs, during
climate warmings there grew broad-leaved forests. However, during the
last glacial period (LGM) all the environs of the cave were occupied by
coniferous forests (Pinhasi et al., 2014).
The
cave Kotias Klde is located in the Chiatura region near the village
Sveri at an altitude of 719 m a.s.l. and occupation levels are dated to
10,900−9940 cal. BP (Meshveliani et al., 2006).
Landscapes around the cave are partially agricultural and partially
covered with deciduous forests of hornbeam, oak, chestnut and beech.
Clearings contain many azalea thickets (Rhododendron luteum Sweet). The climate is warm and humid ( Bondyrev et al., 2014).
Altogether,
9 samples were obtained from the Upper Palaeolithic layers. In
addition, samples of modern sediments were taken inside the cave, at the
entrance, and around the cave. The pollen spectra of the material
considered here documents that 11,000−10,000 years ago the climate
around the cave Kotias Klde remained cool, since pine pollen is
predominant.
The cave Bondi is 6 km away from Chiatura, by the village Tsirkvali (Fig. 1).
Its elevation is 477 m a.s.l. The absolute age of the earliest layers
is 38,700−35,000 cal. BP, while the upper layers (layer III) date to
26,600−14,000 cal. BP (Tushabramishvili et al., 2013).
The cave is located on a bluff of the river Tabagrebi and the
landscapes are domesticated, occupied by gardens and crops. The climate
is warm and humid (Bondyrev et al., 2014).
It
is a rather large karst cave and 11 samples (Profile 1 and floor) were
taken from the Upper Palaeolithic layers and investigated (Tushabramishvili et al., 2009).
The lowest layers VII–V corresponding to the layer D from the cave
Dzudzuana also reflect colder climatic conditions when the cave was
surrounded by coniferous forests with admixture of fir. The upper layers
formed during the LGM cooling were distinguished by more severe
climatic conditions, and in the landscape, spruce and pine became more
important.
2.2. Method
The
laboratory treatment was carried out as follows: first, 50 g of the
sample was boiled in 10% KOH. The solution was washed with distilled
water and settled. At the second stage, centrifuging of the material in
cadmium liquid was performed. At the final stage, acetolysis treatment
was used. Identification and counting of the material was conducted in
glycerine on a light photomiscroscope Olympus BX43 with magnifications
up to 1000×.
Existing atlases, publications and comparative collections of recent material were used in identification. The determination of C. jacea
is based on descriptions and micrographs of pollen grains from pollen
atlases of Reille (1992) and Beug (2004). The morphology of pollen
grains from A.a annua, A. absinthium, A. millefolium, U. dioica
is described in detail by various authors (Kuprianova and Alyoshina
1978; Reille 1992; Beug 2004). To plot the diagrams, the “Tilia”
software ( Grimm, 2004) was used. In all block-diagrams ( Fig. 3, Fig. 4, Fig. 5 and Fig. 6) the absolute abundances (number of pollen grains) are shown. The relative abundances shown in Fig. 7 and Fig. 8 are based on the pollen sum of the five species investigated in this study.
2.3. Characteristics of pollen spectra of modern sediments inside and outside the caves
Modern
samples have been studied from the Dzudzuana, Satsurblia, and Kotias
Klde, caves that also contain archaeological material. Surface samples
have also been taken from another three karst caves in the same region:
Khvedelidzeebis, Samercxle and Datvis Klde caves (Fig. 1). The results of palynological studies are shown in Table 1 and Fig. 2. The presence of five important medicinal species – A. absinthium L. (Asteraceae), A. annua L. (Asteraceae), A. millefolium L. (Asteraceae), C. jacea L. (Asteraceae), and U. dioica
L. (Urticaceae) – in the landscapes of the region is recorded perfectly
in the palynological spectra of the samples from outside the caves.
However, as for the modern spectra of the samples taken from within the
caves, they are either not reflected or the amount of pollen is strongly
underestimated. The presence of nettle (U. dioica) pollen is
especially poorly recorded in the palynological spectra of the caves,
although in soils and mosses around the caves Satsrublia and
Khvedelidzeebis its pollen was found in fairly large amounts ( Table 1). Wormwood pollen (from the few species of Artemisia)
is also poorly reflected in the spectra inside the cave, but in the
subfossil spectra outside the cave its pollen is rather well
represented. The quantity of A. millefolium pollen and C. jacea pollen grains are also three and four times lower inside the caves compared to outside.
- Table 1. Abundance of pollen in modern pollen spectra.
Caves Achillea millefolium L.
Centaurea jacea L.
Urtica dioica L.
Artemisia
Inside Outside Inside Outside Inside Outside Inside Outside Dzudzuana Cave 2 9 1 2 1 1 1 Satsurblia Cave 3 4 7 1 4 Kotias Klde Cave 7 2 2 16 Khvedelidzeebis Cave 11 25 7 11 3 10 1 15 Samertskhle Klde Cave 7 22 1 4 2 3 Datvis Cave 4 5 2 2 Total sum of pollen 20 70 9 28 3 24 3 41
- Fig. 2.Pollen of investigated medicinal plants: 1,2,3-Centaurea jacea from Satsurblia Cave; 4,5-Urtica dioica from Satsurblia Cave; 6,7-Artemisia absinthium from Bondi Cave; 8-Achillea millefolium from Dzudzuana Cave; 9-Artemisia annua from Dzudzuana Cave;10- Centaurea jacea from Bondi Cave; 11,12-Centaurea jacea from Kotias Klde Cave; 13-Centaurea jacea from Dzudzuana Cave;14,15-Achillea millefolium from Kotias Klde Cave; 16-Artemisia absinthium from Kotias Klde Cave; 17-Artemisia annua from Satsurblia Cave.
Thus we can conclude that: 1) nettle (U. dioica)
pollen is generally not transported into caves by wind in the study
region and is most abundant directly near source plants; 2) Artemisia pollen is also very poorly dispersed; 3) the majority of the yarrow (A. millefolium) and knapweed (C. jacea) pollen (70–80%) is also accumulated near populations of these plants.
Poor wind-dispersal of pollen grains of Achillea and Urtica as well as of Centaurea and Artemisia in the humid zones of the Caucasus is indicated not only by sub-recent spectra of soils and mosses ( Stuchlik and Kvavadze, 1987), but also by the results of pollen monitoring conducted in Georgia since 1996 ( Kvavadze, 1999, Kvavadze, 2001, Hicks et al., 2001, van der Knaap et al., 2010 and Kvavadze et al., 2009a).
3. Archaeological and palynological results from Palaeolithic layers
3.1. Cave Dzudzuana
In this cave, there are four stratigraphic layers belonging to the Palaeolithic and the Upper Eneolithic (Bar-Yosef et al., 2011).
Unit D (36,000−31,000 cal. BP) represents the early Upper Palaeolithic
tool-kit of unidirectional short blades and small bladelets. The lithic
industry in Unit C (27,000−24,000 cal. BP) is dominated by small
bladelets detached from carinated cores. Unit B (16,000−13,000 cal. BP)
is rich in blades and bladelets removed from bipolar cores, shaped into
microgravettes, elongated straight-backed items and numerous end
scrapers. Unit A (6000−5000 cal. BP) represents admixture of Late
Neolithic/Eneolithic and historical occupations. All the units contain
worked bone artifacts, including a perforated needle from Unit C, as
well as groundstone utensils and faunal remains.
During
the accumulation of layers D and C in Dzudzuana Cave, humans occupied
the cave for a sustained period and, in addition to the abundance of
stone tools, numerous charred tracheal cells of wood left after the
fire, as well as fibres of flax yarn or textile were found (Bar-Yosef et al., 2011).
However, at the boundary of the D and C layers (after 27,000 cal. BP) a
significant deterioration of climatic conditions is observed (Kvavadze et al., 2012).
Archaeological and palynological data suggest that during the said
cooling, humans abandoned the cave. The cave was then occupied by wild
animals, whose presence was recorded in the spectra by spores of
coprophilous fungi and microscopic remains of mites and insects that
parasitized on animals (Kvavadze et al., 2010b).
During the formation of the upper part of layer C, the climate again warmed, and humans returned to Dzudzuana Cave (Bar-Yosef et al., 2011). In Unit D and the upper part of Unit C, textile fibres, tracheal cells of burnt wood and Pooidea phytoliths indicate that humans lived in the cave. Pollen spectra of this period contain a significant amount of A. absinthium L., A. annua L., A. millefolium L., C. jacea L., and U. dioica L. pollen ( Fig. 2 and Fig. 3).
Pollen grains of these plants are observed in all five studied
profiles. In this paper we give the results for the profile where, on
the whole, the highest amount of plant pollen and spores have been
counted. The pollen diagram of profile II ( Fig. 3)
clearly shows that more intensive habitation of the cave occurred
during the accumulation of the upper part of the layer D. Here, the
increase in pollen of edible plants and medicinal herbs is clearly seen.
For example, the quantity of pollen of wild grasses eaten by people
increases. Carduus (its young green twigs are sweet and juicy), Polygonum and Chenopodiaceae are also edible. In the D-5 layer, the content of hazel (Corylus), walnut (Juglans) and vine (Vitis) pollen increases, since these plants were also part of the diet of Stone Age communities.
- Fig. 3.Absolute abundances of pollen from the investigated species in Profile II from Dzudzuana Cave; the right column gives the total sum of pollen grains in the samples.
3.2. Cave Satsurblia
In
this cave, 22 samples have been studied, but in this paper we give the
results only for 10 studied samples (from the Upper Palaeolithic
layers). Their pollen spectra also contain medicinal herbs, including C. jacea L., A. annua L., A. absinthium L., A. millefolium L. and U. dioica L. ( Fig. 4). U. dioica pollen grains were also found in the second and the third floor layers ( Pinhasi et al., 2014).
In these samples, the amount of pollen of edible plants (hazelnut,
chestnut, beech, wild grasses, etc.) increases, which shows that during
the accumulation of the layers from which samples 16 and 19 were taken,
humans had been living in the cave for quite a long time. The continued
presence of humans, in addition to the archaeological and palynological
material, is also recorded by an increase in the amount of flax textile
fibres and charred tracheal cells of wood left after fires.
- Fig. 4.Absolute abundances of pollen from the investigated species in the Upper Palaeolithic layers of Satsurblia Cave; the right column gives the total sum of pollen grains in the samples.
3.3. Cave Kotias Klde
Pollen of many medicinal plants is well represented in the Upper Palaeolithic layers of the cave Kotias Klde (Fig. 5).
- Fig. 5.Absolute abundances of pollen from the investigated species in the Upper Palaeolithic layers of Cave Kotias Klde; the right column gives the total sum of pollen grains in the samples.
In the Upper Palaeolithic layers, the maximum content of C. jacea, A. annua, A. absinthium, A. millefolium and U. dioica
pollen is observed in samples 5 and 6. Here, there are also large
quantities of pollen of edible plants and especially of chestnut (Castanea), hazel (Corylus), walnut (Juglans) and wild grasses (Poaceae), which indicates human habitation in the cave for prolonged periods.
3.4. Cave Bondi
Despite the fact that this karst cave contained rather small quantities of pollen (Tushabramishvili et al., 2009), medicinal plant pollen grains were found in nearly all studied layers (Fig. 6). Wormwood (A. annua) pollen was recorded in the bottom and top layers of the profile. Yarrow (A. millefolium) and brown knapweed (C. jacea) are better represented in top layer 2. Pollen grains of nettle (U. dioica)
were not found at all, which might be explained by poor conditions of
pollen preservation. Of edible plants, the pollen of wild grasses
(Poaceae), hazel (Corylus), dogwood (Cornus), buckwheat (Polygonum aviculare, Polygonum-type)
was found in the Upper Palaeolithic layers of Bondi cave. In the layers
accumulated during the long human habitation, an increase in the amount
of flax and wool textile fibres and tracheal cells of charred wood is
observed. These non-pollen palynomorphs belong to the group of
anthropogenic indicators ( Tushabramishvili et al., 2009 and Tushabramishvili et al., 2013).
- Fig. 6.Absolute abundances of pollen from the investigated species in the Upper Palaeolithic layers of Bondi Cave; the right column gives the total sum of pollen grains in the samples.
4. Some phytochemical and pharmacological data on the studied species
4.1. Achillea millefolium L.
A. millefolium
L. prefers open and dry slopes, though it also grows near human
dwellings, along the roads and in waste places. It is considered a
ruderal plant ( Radusiene and Gudaityte, 2006, Gagnidze, 2007 and Nakhutsrishvili, 2013). The main pharmacological components of A. millefolium
are flavonoids, phenolic acids, alkaloids, terpens (cineol, borneol,
pinens, camphor, azulen), tannins, cis-Carveol, achillin and leucosis ( Shahbazi and Zadeh, 2008, Bimbirait et al., 2008, Raju et al., 2009, Lakshmi et al., 2011 and Feizpour et al., 2013). Flavonoids and phenol carbonic acids of yarrow constitute the most important groups of pharmacologically active substances ( Shahbazi and Zadeh, 2008, Bimbirait et al., 2008, Raju et al., 2009, Lakshmi et al., 2011 and Feizpour et al., 2013). The most noticeable effects of this plant are on antioxidant and antimicrobial activity ( Candan et al., 2003 and Lakshmi et al., 2011); anti-inflammatory ( Goldberg et al., 2006); antihypertensive, bronchodilatory, ( Khan and Gilani, 2011), gastrointestinal antispasmodic (cramps, indigestion, epigastric distension, flatulence, and intestinal colic), ( Benedek and Kopp, 2007 and Lakshmi et al., 2011), diuretic, urinary antiseptic ( Bag et al., 2008) and astringent and antihemorrhagic effects ( Işcan et al., 2006).
According to the traditions of folk medicine, A. millefolium is mainly used for the treatment of gastrointestinal diseases, anaemia and as antistyptic ( Odisharia and Sabakhtarashvili, 1993, Chevallier, 1996, Moerman, 1998, Menković et al., 2011, Zlatović et al., 2014 and Jamila and Mostafa, 2014). According to other authors, yarrow treats diabetes, hypertension and can be used as an antimicrobial agent ( Said et al., 2002 and Hassawi and Kharma, 2006).
It has also traditionally been used as an abortifacient, emmenagogue,
contraceptive, and for stimulating uterine contractions ( Lakshmi et al., 2011). For this reason, it is contra-indicated for use in pregnancy. There has, however, been little scientific research ( Lakshmi et al., 2011).
4.2. Artemisia annua L.
A. annua L. as a medicinal plant was first investigated in 1971 in China, and the medicine made from it had the name artemisinin ( White, 2008).
Artemisinin is a key-ingredient in the leading treatment for malaria
and is an extract of an ancient medicinal plant. The re-discovery of A. annua as a medicinal plant reveals something that Dalrymple (2008) calls a “golden triangle” – an interaction between traditional medicine, modern medicine and science ( Mueller et al., 2004, Ferreira, 2004, Mamedov and Craker, 2008, Adams et al., 2009 and Meier zu Biesen, 2010). A. annua produces at least 36 flavonoids. Many of these have antimalarial activity in vitro,
although the inhibitory concentration is 50% (IC50). Five of these,
artemetin, casticin, chrysoplenetin, chrysosplenol-D, and cirsilineol,
have been shown selectively to affect the in vitro activity of artemisinin against Plasmodium falciparum ( Liu et al., 1992).
The effect of all the flavones in combination with artemisinin has not
yet been investigated. Other flavones, and indeed other components of A. annua,
may have a similar effect; they have not all been tested because it is
difficult to purify them. The antimalarial properties of the traditional
preparation of A. annua most probably reside in the combination of many constituents, not just artemisinin (see Willcox et al., 2004).
The fact that artemisinin-based combination therapies are ‘ancient’ in
their use and ‘modern’ in their formulation shows the transformative
potential of the plant itself (see Meier zu Biesen, 2010).
4.3. Artemisia absinthium L.
A. absinthium L. is a ruderal plant ( Radusiene and Gudaityte, 2006, Gagnidze, 2007 and Nakhutsrishvili, 2013). Flavonoids, tannins, glucosides, carotenoids, andphenolic compounds are major phytoconstituents of A. absinthium ( Nikhat et al., 2013). Flavonoids components include quercitin 3-glucoside and 3-rhamnoglucoside, spinacetin 3-glucoside and 3-rhamnoglucoside ( Nikhat et al., 2013).
One drug derived from wormwood is Afsantin, which has been reported as
an anti-inflammatory, antipyretic, hepatoprotective, antidepressant,
antioxidant, deobstruents, analgesic, antiseptic and antimicrobial ( Dettling et al., 2004, Lopes-Lutz, 2008, Carner, 2008, Movilla Pires, 2009, Mahmoudi et al., 2009, Tariq, 2009, Amat and Upur, 2010, Karabegoviæ, 2011, Singhal and Gupta, 2012, Saxena and Shukla, 2012 and Efferth, 2014).
Owing to these properties, it has been used to treat various diseases,
such as atherosclerosis, cardiovascular diseases, fever, abdominal pain,
intestinal worms, cognitive dysfunctions, hepatitis, malarial fever,
cancer and rheumatism ( Halliwell, 1997, Nikhat et al., 2013 and Menale and Muoio, 2014).
Research shows that it is highly effective and carries a low risk of
toxicity and side effects. There is a need to scientifically establish
its efficacy and safety in order to achieve global acceptance ( Nikhat et al., 2013).
4.4. Centaurea jacea L.
In the Caucasus C. jacea generally grows on forest edges and in clearings ( Agababyan and Fajvush, 1991, Agababyan, 1997, Gagnidze, 2007 and Nakhutsrishvili, 2013).
Different
types of secondary metabolites (flavonoids, sesquiterpenes) were found
to be responsible for the anti-tumour effects of extracts of C. jacea;
the highest activity was exerted by centaureidin, in addition to
moderately active compounds: cirsiliol, isokaempferide, apigenin,
hispidulin, cnicin and 4′-acetylcnicin ( Forgo et al., 2012). The chloroform extract of C. jacea
afforded the isolation of cirsiliol, apigenin, hispidulin, eupatorin,
isokaempferide, axillarin, centaureidin, 6-methoxykaempferol 3-methyl
ether, trachelogenin, cnicin, 4′-acetylcnicin and three aliphatic
glucose diesters, including the new natural product
1β-isobutanoyl-2-angeloyl-glucose ( Forgo et al., 2012).
In the Turkish folk medicine C. jacea was particularly recommended against inflammatory conditions and to reduce fever ( Yesilada, 2002).
Other species of Centaurea have been used in traditional medicine as a diuretic and to treat fever and diabetes ( Font Quer, 1995). Many Centaurea were added to tonics in the belief that they stimulate the flow of saliva and stomach acids, returning appetite to invalids ( Bernhardt, 2008). Centaurea
species are famous in folk medicine to have anti-diarrheic,
anti-dandruff, anti-rheumatic, anti-inflammatory, cholagogue,
choleretic, digestive, stomachic, menstrual, astringent, hypotensive,
anti-pyretic, cytotoxic as well as anti-bacterial effects and are used
alone or mixed with other plants ( Farrag et al., 1993, Barrero et al., 1997, Orallo et al., 1998 and Köse et al., 2007).
4.5. Urtica dioica L.
U. dioica L. (nettle), being a ruderal species, grows in trampled, shaded areas along paths and near human dwellings ( Gagnidze, 2007 and Nakhutsrishvili, 2013).
Nettle leaves contain 1–2% flavonoids, (particularly glycosides and
rutosides of quercetin, kaemferol and isohamnetin). The herbal substance
contains silicates in a relatively large quantity (1–4% SiO2)
partly as water-soluble silicates. Characteristic components are
scopoletin, sitosterol with its 3-O-βD-glucoside and caffeic acid
esters. Other constituents include chlorophyll (approximately 2.7%),
proteins, fats, carbohydrates, traces of nicotine and, in the stinging
hairs, small amounts of acetylcholine, serotonin, formic acid and
leukotrines ( Asgarpanah and Mohajerani, 2012 and Wichtl, 2002). According to other authors, alkaloids, tannins and terpenoids are present in nettles ( Kais Kassim Ghaima et al., 2013). The available literature shows that U. dioica L. has antioxidant ( Kanter et al., 2005), anti-inflammatory ( Hajhashemi and Klooshani, 2012), anti-ulcer ( Gülçin et al., 2004), anticancer, antimicrobial ( Nisha et al., 2011), cardiovascular ( Asgarpanah and Mohajerani, 2012) and hepatoprotective ( Kanter et al., 2005) properties.
U. dioica is considered a good remedy for rheumatism, asthma, anaemia and gout ( Launert, 1981, Foster and Duke, 1990, Adams et al., 2009, Hayta et al., 2014 and Zlatović et al., 2014). Moreover, nettles are used to treat burns, viral, bacterial and fungal diseases ( Foster and Duke, 1990 and Adams et al., 2009). Nettle is also a good pain reliever for rheumatism ( Randall et al., 1999, Bown, 1995 and Hajhashemi and Klooshani, 2012).
New investigations showed that these recent results confirm the
folkloric use of the plant extract to treat painful and inflammatory
conditions. Further studies are needed to characterise the active
constituents and the mechanism of action of the plant extract ( Hajhashemi and Klooshani, 2012).
5. Discussion
The study of modern spectra of cave sediments inside and outside the cave and the significant representation of C. jacea L., A. annua L., A. absinthium L., A. millefolium L. and U. dioica
L. pollen showed that pollen grains of these species in the study
region are not always transported by wind over long distances. Therefore
the amount of their pollen in present-day caves tends to be very small.
However, they are quite well represented in the palynological spectra
of sediments taken outside the cave. In this regard, the substantial
presence of pollen from medicinal species – C. jacea, A. annua, A. absinthium, A. millefolium and U. dioica –
in the Upper Palaeolithic layers of the caves is best explained by the
fact that humans brought their flowering branches inside for their
needs. Thus, the presence of C. jacea, A. annua, A. absinthium, A. millefolium and U. dioica,
established by the pollen found in the cultural layers in all four
studied Upper Palaeolithic caves, may help to reveal many details of
palaeopharmacology and diseases of prehistoric humans. As already noted,
there are currently very few data on Upper Palaeolithic
palaeopharmacology, so palynology is very important for finding
solutions to this problem ( Chaves and Reinhard, 2003).
The overview of the literature on the therapeutic properties of the
studied plants shows a fairly wide range of applications for all five
species ( Table 2). Nettle (U. dioica) is unique as it has the largest number of indications for treating many (about 14) diseases ( Kais kassim Ghaima et al., 2013). Yarrow (A. millefolium)
has more than 11 pharmacological properties. The common pharmacological
characteristics of the studied species provide insights into the
prevailing medical conditions among the cave׳s Palaeolithic population.
For example, all species except A. annua have an
anti-inflammatory activity. Antibacterial, antimicrobial and antipyretic
activities are also common traits (Plate 2) for these species. On the
whole, the five studied species can treat a very large number of
diseases. It is probable that 35−25 thousand years ago, people might
have known the medical properties of these species, collected them and
used them for treating illnesses.
- Table 2. List of medicinal plant species (which pollen found in Upper Palaeolithic sediments) used in traditional medicine.
In the Dzudzuana cave, U. dioica, according to palynological data, was an important remedy in the Upper Palaeolithic ( Fig. 7a); it accounts for 35% of the total counted pollen of the five studied species.
- Fig. 7.Relative abundances of pollen from the investigated medicinal plants in the different caves; a-Dzudzuana Cave; b-Satsurblia Cave; c- Kotias Klde Cave; d-Bondi Cave.
In
the cave Satsurblia, the content of nettle pollen grains is 15%, but in
the layers of the Kotias Klde cave, this figure does not exceed 6%, and
in the Bondi cave nettle pollen is not found at all (Fig. 7b).
It should also be noted that the people could not eat raw, unprocessed
nettle because of its sting. The lack of pottery suggests that nettle
could not be cooked. However, there were stone mortars and cups, one of
which was found in the Dzudzuana cave (Meshveliani et al., 2009),
which were used to grind not only nettle, but also many seeds, roots
and fruits of medicinal plants. This mortar-ground nettle was probably
applied to wounds or aching joints.
In folk medicine, nettle (U. dioica) is considered to be a good remedy for rheumatism, asthma, anaemia and gout ( Launert, 1981, Foster and Duke, 1990, Adams et al., 2009, Hayta et al., 2014 and Zlatović et al., 2014). Moreover, in folk medicine, nettle is often used to treat burns, viral, bacterial and fungal diseases ( Foster and Duke, 1990 and Adams et al., 2009). Nettle is also a good pain reliever for rheumatism ( Randall et al., 1999, Bown, 1995 and Hajhashemi and Klooshani, 2012). It should be mentioned here that, besides nettle, antirheumatic properties are also characteristic for the medicinal plant A. absinthium, which was also found in the layers of the Dzudzuana cave and accounts for 4% of the pollen. A. annua
content reaches 26% in the same layers. Antimalarial activity is a
common trait in the pharmacological properties of these two wormwood
species ( Table 2).
This may indicate that the ancient inhabitants of Dzudzuana, besides
rheumatism, also suffered from malaria. In the Dzudzuana layers, A. millefolium
pollen content is rather high and accounts for 28%. This plant differs
from all other studied species by having gastrointestinal antispasmodic
properties. Yarrow is also a good antidepressant ( Table 2).
According to the tradition of folk medicine, yarrow is mainly used for the treatment of gastrointestinal diseases and anaemia (Odisharia and Sabakhtarashvili, 1993, Chevallier, 1996, Moerman, 1998, Menković et al., 2011, Zlatović et al., 2014 and Jamila and Mostafa, 2014). According to other authors, yarrow treats diabetes and hypertension and can be used as an antimicrobial agent (Said et al., 2002 and Hassawi and Kharma, 2006).
As for the C. jacea
pollen grains, their content is not high, and reaches only 7%. Brown
knapweed is used in folk medicine as a remedy to reduce fever, diabetes,
anaemia, cholecystitis, gastritis and as an antifungal agent ( Yesilada, 2002, Said et al., 2002 and Khammar and Djeddi, 2012).
Based
on the quantitative composition of the studied species, we can conclude
that the ancient population of Dzudzuana cave suffered from several
diseases, with a predominance of rheumatism, malaria, asthma and gastric
diseases.
In the cultural layers of the Satsurblia cave, A. millefolium pollen is predominant and accounts for 45% of the content of all five species ( Fig. 7b).
This may indicate that the ancient population of the Satsrublia
neighbourhood was in greater need of this remedy. Yarrow, as already
noted, is used in folk medicine mainly to treat gastric diseases. Yarrow
is also a urinary antiseptic and diuretic ( Table 2).
In the Upper Palaeolithic layers of Satsurblia cave, the second dominant after yarrow pollen is C. jacea (25%), which treats gastritis, anaemia, reduces fever and diabetes ( Table 2). The pollen of two species of wormwood ( Fig. 7b) accounts for 15% (10% A. annua and 5% A. absithium). The presence of Artemisia
pollen suggests the existence of malaria and rheumatism in the
Satsurblia area. The population might have treated rheumatism using
nettle, the pollen content of which is 15% ( Fig. 7b).
The percentage of pollen of medicinal plants in the Upper Palaeolithic layers of the Kotias Klde cave is noteworthy. Here A. millefolium pollen is predominant and accounts for 46% ( Fig. 7c).
This means that the local population had a great need for yarrow, i.e.
stomach and urological diseases may have been widespread here. C. jacea was also collected and stored; in the palynological spectra it accounts for 20%. The content of A. annua is slightly less than the brown knapweed and accounts for 18%. The share of A. absinthium is 9%. Nettle pollen was not found in large quantities (6%).
The palynological spectra of the Bondi cultural layers (Fig.7d) are dominated by A. annua pollen (58%). The second most prevalent is A. millefolium (19%). C. jacea pollen accounts for 14%. Large amounts of A. annua
collected and used by the Bondi population may be explained by the
widespread occurrence of malaria at that time. This would have been
facilitated by its proximity to the river, the banks of which might have
been swampy. A. millefolium and C. jacea were used to treat other diseases mentioned above
Thus,
summarizing the data for all studied caves, we can see that the Upper
Palaeolithic population used a great deal of yarrow (Fig. 8), which in modern medicine, as noted above, treats more than 14 diseases. A. annua was also extensively used.
- Fig. 8.Total relative abundances of pollen from the investigated medicinal plants summed up for all investigated caves.
A comparison of the total amount of pollen of the five examined genera in the studied caves (Fig. 8) shows that they have different quantities of wormwood (A. annua and A. absinthium), yarrow (A. millefolium), nettle (U. dioica) and brown knapweed (C. jacea)
pollen. The question arises: what caused such a significant difference
in the percentage of medicinal herbs in the above four caves? For
example, why was nettle more widely used by ancient people living in the
Dzudzuana cave than by residents of other caves? The reasons could
certainly be different. Primarily, the said plant genera, depending on
local geographical conditions in the surrounding environment, may have
had a different distribution. Nettle (U. dioica), being a
ruderal species, grows in trampled, shaded areas along paths and near
human dwellings. Animals do not usually eat it, and therefore its
thickets develop quite rapidly.
A. millefolium grows perfectly on pastures, and owing to its strong smell, it is not eaten by herbivores. Animals do not eat any species of Artemisia,
since this plant is bitter. Being a ruderal plant, it grows abundantly
in trampled places, along the roads and paths and near human dwellings.
As for C. jacea, it grows on forest edges and clearings ( Agababyan and Fajvush, 1991, Agababyan, 1997, Gagnidze, 2007 and Nakhutsrishvili, 2013).
Local
geomorphological and geographical conditions could also have influence
on the nature of the most common diseases of the population in the late
Palaeolithic. For example, even at present, the humid climate in western
Georgia (and especially in Imereti due to the proximity of the Black
Sea and the western transport of air masses) causes rheumatism and
arthritis in the local population. Until the advent of appropriate
medicines and mosquito control programmes, malaria was widespread in the
study region. In our opinion, these diseases existed in the Upper
Palaeolithic, since in the identified set of medications there were
plants for treating malaria and rheumatism. The caves located in the
gorges (Dzudzuana Cave and Bondi Cave) and along the rivers were
characterised by high dampness, perhaps making their occupants more
prone to malaria and rheumatism than people living in the caves located
in open and dry places (Satsrublia and Kotias Klde).
In the Upper Palaeolithic, the biggest problem for the population living in cave dwellings was probably gout and callouses.
Since
most herbs are ruderal, communities of the Upper Palaeolithic used for
medical purposes essentially those plants that grew near their
dwellings.
6. Conclusion
The study of modern spectra of cave sediments inside and outside the cave and of the role of C. jacea L., A. annua L., A. absinthium L., A. millefolium L. and U. dioica
L. pollen showed that pollen grains of these species in the study
region are not transported by wind over long distances and therefore in
caves their pollen content is very low.
In the Upper Palaeolithic layers, significant amounts of C. jacea, A. annua, A. absinthium, A. millefolium and U. dioica pollen were recorded in the cave, likely due to their flowering branches being brought in by humans for use.
Detailed
consideration of the pharmacological characteristics of the examined
species showed that almost all of them have anti-inflammatory,
antibacterial, antimicrobial and antipyretic activity and could be used
successfully for the treatment of many inflammatory diseases.
The fossil pollen complex of medicinal herbs, dominated by A. millefolium and A. annua,
suggests that the ancient population living in the studied caves could
have been prone to rheumatism, malaria and gastrointestinal diseases.
In the Upper Palaeolithic, the population inhabiting cave sites might have suffered from gout and callouses.
The
population of the caves located in the gorges and along the rivers and
characterised by high dampness was probably more prone to malaria and
rheumatism than people living in the caves located in open and dry
places.
Acknowledgements
We
thank Dr. Tengiz Meshveliani, Dr. Nino Jakeli, Prof. Ofer Bar-Yosef,
Prof. Anna Belfer-Cohen, Dr. Zinovi Matskevich, Prof. Nikoloz
Tushabaramishvili, Dr. Tamar Agapishvili, Dr. Rusudan Chagelishvili, Dr.
Shalva Barjadze, Prof. Antonio Sagona, Dr. Simon Connor and Dr. Angela
Bruch for helpful comments and help in fieldwork.
References
- Agababyan and Fajvush, 1991
- Centaurea in the Caucasus
- Thaiszia Košice, 1 (1991), pp. 49–53
- Agababyan, 1997
- Centaurea subg. Centaurea (Compositae): delimitation and distribution of sections and subsections
- Lagascalia, 19 (1–2) (1997), pp. 889–902
- Amat and Upur, 2010
- In vivo hepatoprotective activity of the aqueous extract of Artemisia absinthium L. against chemically and immunologically induced liver injuries in mice
- J. Ethnopharmacol., 131 (2) (2010), pp. 478–484
- | | |
- Arobba and Caramiello, 2009
- Archaebotanical studies from Neolithic layers of the Pian del Cilieglo roch shelter (Finale Ligure, Savona)
- Quad. Mus. Archeol. Final., 5 (2009), pp. 117–130
- |
- Asgarpanah and Mohajerani, 2012
- Phytochemistry and pharmacological properties of Urtica dioica L.
- J. Med. Plants Res., 6 (2012), pp. 5714–5719
- Bag et al., 2008
- Medicinal plants and urinary tract infections, an update
- Pharmacogn. Rev., 24 (2008), pp. 277–284
- |
- Barrero et al., 1997
- Cytotoxic Activity of Flavonoids from Carthamus arborescens, Ononis natrix ssp. ramosissima and Centaurea malacitana
- Fitoterapia, 68 (1997), pp. 281–283
- |
- Bar-Yosef et al., 2011
- Dzudzuana: an Upper Palaeolithic cave site in the Caucasus foothills (Georgia)
- Antiquity, 85 (2011), pp. 331–349
- |
- Benedek and Kopp, 2007
- Achillea millefolium L. s.l. revisited: recent findings confirm the traditional use
- Wien. Med. Wochenschr., 157 (2007), pp. 312–314
- | |
- Bernhardt, 2008
- Gods and Goddesses in the Garden: Greco-Roman Mythology and the Scientific Names of Plants
- Rutgers University Press, United States (2008)
- Bimbirait et al., 2008
- Comparison of the chemical composition of four yarrow (Achillea millefolium L.) morphotypes
- Biologija, 54 (2008), pp. 208–212
- Bondyrev et al., 2014
- The Geography of Georgia, problems and perspectives
- Springer (2014)
- Bown, 1995
- Encyclopaedia of Herbs and Their Uses
- Dorling Kindersley, London (1995)
- Burney and Burney, 1993
- Modern pollen deposition in cave sites: experimental results from New York State
- New Phytol., 124 (1993), pp. 523–535
- | |
- Candan et al., 2003
- Antioxidant and antimicrobial activity of the essential oil and methanol extracts of Achillea millefolium subsp. millefolium Afan. (Asteraceae)
- J Ethnopharmacol., 87 (2003), pp. 215–220
- | | |
- Carrión, 1992
- A Palaeoenvironmental study in semi-arid Southeastern Spain: the palynological and sedimentological sequence at Perneras Cave (Lorca, Murcia)
- J. Archaeol. Sci., 22 (1992), pp. 355–367
- Carrión et al., 1999
- The palaeoecological potential of pollen records in caves: the case of Mediterranean Spain
- Q. Sci. Rev., 18 (1999), pp. 1061–1073
- | | |
- Carner, 2008
- Comparison of the effects of Artemisia vulgaris and Artemisia absinthium growing in western Anatolia against trichinellosis (Trichinella spiralis) in rats
- Exp. Parasitol., 119 (1) (2008), pp. 173–179
- Chaves and Reinhard, 2003
- Paleopharmacology and pollen: theory, method, and application
- Mem. Inst. Oswaldo Cruz, 98 (Suppl. I) (2003), pp. S207–S211
- Dettling et al., 2004
- Absinthe: attention performance and mood under the influence of thujone
- J. Stud. Alcohol, 65 (2004), pp. 573–581
- | |
- Efferth, 2014
- The antiviral activities of Artemisinin and Artesunate: stability and antiviral activity against human cytomegalovirus of artemisinin derivatives
- J. Antimicrob. Chemother., 69 (1) (2014), pp. 34–40
- Eugenia de Porras et al., 2011
- Modern pollen analysis in caves at the Patagonian steppe, Argentina
- Rev. Palaeobot. Palynol., 166 (2011), pp. 335–343
- Eshleman, 2003
- Upper Paleolithic imagination & the Construction of the Underworld
- Published by Wesleyan University Press, Middletown (2003), pp. 161–167
- Farrag et al., 1993
- Phytochemical investigation of Centaurea araneosa growing in Egypt, Zag
- J. Pharm. Sci., 2 (1993), pp. 29–45
- |
- Feizpour et al., 2013
- The effect of hydro-ethanolic extract of Achillea millefolium on muscarinic receptors of guinea pig tracheal smooth muscle
- Indian J Pharmacol., 45 (1) (2013), pp. 13–17
- | |
- Font Quer, 1995
- Plantas Medicinales. El Dioscorides Renovado
- (15th ed.)Editorial Labor S.A, Madrid (1995)
- Forgo et al., 2012
- Bioactivity guided isolation of antiproliferative compounds from Centaurea jacea L.
- Fitoterapia, 83 (2012), pp. 921–925
- | | |
- Foster and Duke, 1990
- Peterson Field Guide Series: A Field Guide to Medicinal Plants, Eastern and Central North America
- Houghton Mifflin, Boston (1990), p. 212
- Gagnidze, 2007
- Flora of Georgia
- R. Gagnidze (Ed.)Vol.27Metsniereba, Tbilisi (2007)
- Goldberg et al., 2006
- Isolation of the anti inflammatory principles from Achillea millefolium (compositae)
- J. Pharma. Sci., 58 (2006), pp. 938–941
- Gülçin et al., 2004
- Antioxidant, antimicrobial, antiulcer and analgesic activities of nettle (Urtica dioica L.)
- J. Etnopharmacol., 90 (2004), pp. 205–215
- | | |
- Hajhashemi and Klooshani, 2012
- Antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in animal models
- Avicenna J. Phytomed., 3 (2) (2012), pp. 193–200
- Halliwell, 1997
- Antioxidants and human diseases: a general introduction
- Nutr. Rev., 55 (1997), pp. 44–52
- Hassawi and Kharma, 2006
- Antimicrobial activity of some medicinal plants against Candida albicans
- J. Biol. Sci., 6 (1) (2006), pp. 109–114
- |
- Hayta et al., 2014
- Traditional uses of medicinal plants in Elaziğ (Turkey)
- J. Ethnopharmacol. (2014) http://dx.doi.org.scopeesprx.elsevier.com/10.1016/j.jep.2014.04.026i
- Hicks et al., 2001
- Some comments on spatial variation in arboreal pollen deposition: first records from the Pollen Monitoring Programme (PMP)
- Rev. Palaeobot. Palynol., 117 (2001), pp. 183–194
- | | |
- Işcan et al., 2006
- Biological activity and composition of the essential oils of Achillea schischkinii Sosn. and Achillea aleppica DC. subsp. aleppica
- J. Agric. Food Chem., 54 (2006), pp. 170–173
- | |
- Jamila and Mostafa, 2014
- Ethnobotanical survey of medicinal plants used by people in Oriental Marocco to manage various ailments
- J. Ethnopharmacol., 154 (2014), pp. 76–87
- | | |
- Kais Kassim Ghaima et al., 2013
- Antibacterial and antioxidant activities of ethyl acetate extract of nettle (Urtica dioica) and dandelion (Taraxacum officinale)
- J. Appl. Pharm. Sci., 3 (5) (2013), pp. 096–099
- Kanter et al., 2005
- Hepatoprotective effects of Nigella sativa L. andUrtica dioica L. on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats
- World J. Gastroenterol., 11 (2005), pp. 6684–6688
- |
- Karabegoviæ, 2011
- Comparison of antioxidant and antimicrobial activities of methanolic extracts of the Artemisia sp. recovered by different extraction techniques
- Chin. J. Chem. Eng., 19 (3) (2011), pp. 504–511
- Khammar and Djeddi, 2012
- Pharmacological and Biological Properties of some Centaurea Species
- Eur. J. Sci. Res., 84 (3) (2012), pp. 398–416
- |
- Khan and Gilani, 2011
- Blood pressure lowering, cardiovascular inhibitory and bronchodilatory actions of Achillea millefolium
- Phytother. Res., 25 (2011), pp. 577–583
- | |
- Kvavadze, 1999
- The first results of Pollen Monitoring Programme in the Caucasus mountains (Georgia)
- Acta Palaeobot., 39 (1) (1999), pp. 171–177
- |
- Kvavadze, 2001
- Annual modern pollen deposition in the foothills of the Lagodekhi Reserve (Caucasus, East Georgia), related to vegetation and climate
- Acta Palaeobot., 41 (2) (2001), pp. 355–364
- Kvavadze et al., 2009b
- 30,000-year-old wild flax fibers
- Science, 325 (2009), p. 1359
- | |
- Kvavadze et al., 2010a
- Responze to Comments on “30,000-Year-Old Wild Flax Fibres”
- Science, 328 (2010), p. 1634
- | |
- Köse et al., 2007
- Antimicrobial activity of the essential oil of Centaurea aladagensis
- Fitoterapia, 78 (2007), pp. 53–254
- Lakshmi et al., 2011
- Yarrow (Achillea millefolium Linn.) a herbal medicinal plant with broad therapeutic use – a review
- Int. J. Pharm. Sci. Rev. Res., 9 (2011), pp. 136–141
- |
- Launert, 1981
- Edible and Medicinal Plants
- Hamlyn (1981)
- Leroi-Gourhan, 1975
- The flowers found with Shanidar IV: a neandertal burial in Iraq
- Science, 190 (1975), pp. 562–564
- | |
- Lietava, 1992
- Medicinal plants in a Middle Palaeolithic grave Shanidar IV
- J. Ethnopharmacol., 35 (1992), pp. 263–266
- | | |
- Liu et al., 1992
- Antimalarial activity of Artemisia annua lavonoids from whole plants and cell cultures
- Plant Cell Rep., 11 (1992), pp. 637–640
- |
- Lopes-Lutz, 2008
- Screening of chemical composition, antimicrobial and antioxidant activities of Artemisia essential oils
- Phytochemistry, 9 (8) (2008), pp. 1732–1738
- | | |
- Magyari et al., 2013
- Palaeo-environments of the Balkan Lateglacial and their potential- were humans absent from Garden of Edem?
- Bulg. J. Archaeol., 3 (2013), pp. 1–30
- Mahmoudi et al., 2009
- Antidepressant and antioxidant activities of Artemisia absinthium L. at flowering stage
- Afr. J. Biotechnol., 8 (24) (2009), pp. 7170–7175
- |
- Meier zu Biesen, 2010
- The rise to prominence of Artemisia annua L.- the transformation of a Chinese plant to a global pharmaceutical
- Afr. Sociol. Rev., 14 (2) (2010), pp. 24–46
- Menale and Muoio, 2014
- Use of medicinal plants in the South-Eastern area of the Partenio Region Park (Campania, Southern Italy)
- J. Ethnopharmacol., 153 (2014), pp. 297–307
- | |
- Menković et al., 2011
- Ethnobotanical study on traditional uses of wild medicinal plants in Prokletije Mountains (Montenegro)
- J. Ethnopharmacol., 133 (2011), pp. 97–107
- | | |
- Merlin, 2003
- Archaeological evidence for the tradition of psychoactive plant use in the Old World
- Econ. Bot., 57 (1) (2003), pp. 295–323
- | |
- Meshveliani et al., 2006
- Kotias Klde Cave and the Paleolithic man׳s first burial in Caucasus
- J. Georgian Archaeol., 17–18 (2006), pp. 12–16
- Meshveliani et al., 2013
- The results of the archaeological expedition in Satsurblia Cave in 2012
- J. Georgian Archaeol., 21 (2013), pp. 7–13
- Moerman, 1998
- Native American Ethnobotany
- Timber Press, Oregon (1998)
- Moore et al., 1991
- Pollen Analysis
- Blackwell Scientific Publications, Oxford (1991)
- Movilla Pires, 2009
- Antinociceptive peripheral effect of Achillea millefolium L. and Artemisia vulgaris L.: both plants known popularly by brand names of analgesic drugs
- Phytother. Res., 23 (2) (2009), pp. 212–219
- Mueller et al., 2004
- Randomized controlled trial of a traditional preparation of Artemisia annua L. (Annual Wormwood) in the treatment of malaria
- Trans. R. Soc Trop. Med. Hyg., 98 (5) (2004), pp. 318–321
- | | |
- Nakhutsrishvili, 2013
- The vegetation of Georgia (South Caucasus)
- Pedrotti Franco (Ed.), Geobotany Studies, Basics, Methods and Case Studies, Springer (2013)
- Navarro et al., 2000
- An experimental approach to the palynology of cave deposits
- J. Q. Sci., 15 (2000), pp. 603–619
- Navarro et al., 2002
- Modern Cave pollen in an arid environment and its application to describe palaeorecords
- Complutum, 13 (2002), pp. 7–18
- |
- Nikhat et al., 2013
- Phytochemical and ethmopharmacological perspective of Afsantin (Artemisia absinthium Linn.)
- Ann. Phytomed., 2 (2) (2013), pp. 105–109
- Nisha et al., 2011
- In vitro antifungal potency of plant extracts against five phytopathogens
- Braz. Arch. Biol. Technol., 54 (2011), pp. 1093–1098
- Odisharia and Sabakhtarashvili, 1993
- Medicinal Plants of Georgia and Phytotherapeutic Receipts
- Sinatle Press, Tbilisi (1993)
- Orallo et al., 1998
- Preliminary study of the potential vasodilator effects on rat aorta of Centaurein and Centaureidin, tow flavonoids from Centaurea corcubionensis
- Planta Medica, 64 (1998), pp. 116–119
- | |
- Pinhasi et al., 2014
- Satsurblia: new insights about human response and survival across the Last Glacial Maximum in the southern Caucasus
- PLoS ONE, 9 (10) (2014)
- Petrovska, 2012
- Historical review of medicinal plants usage
- Pharmacogn. Rev., 6 (11) (2012), pp. 1–5
- | |
- Radusiene and Gudaityte, 2006
- Distribution of proazulenes and productivity in Achillea millefolium L. spontaneous populations
- Rev. Bras. Plantas Med., 8 (2006), pp. 155–158
- |
- Randall et al., 1999
- Nettle sting of Urtica dioica for joint pain- an exploratory study of this complementary therapy
- Complement. Ther. Med., 7 (1999), pp. 126–131
- | | |
- Raju et al., 2009
- Evaluation of anti-asthmatic activity of aqueous extract of Achillea mellifolium Linn flowers
- Arch. Appl. Sci. Res., 1 (2009), pp. 287–293
- |
- Roberts and Manchester, 1995
- The Archaeology of Disease
- (2nd ed.)Gloucestershire, Sutton (1995)
- Said et al., 2002
- Ethnopharmacological survey of medicinal herbs in Israel, the Golan Heights and the West Bank region
- J Ethnopharmacol., 83 (2002), pp. 251–265
- | | |
- Saxena and Shukla, 2012
- Reversal of carbon tetrachlorideinduced hepatic injury by aqueous extract of Artemisia absinthium in Sprague–Dawley rats
- J. Environ. Pathol. Toxicol. Oncol., 31 (4) (2012), pp. 325–334
- | |
- Shahbazi and Zadeh, 2008
- In vitro assessment of antimicrobial efficacy of alcoholic extract of Achillea millefolium in comparison with penicillin derivatives
- J. Anim. Vet. Adv., 7 (2008), pp. 508–511
- Singhal and Gupta, 2012
- Hepatoprotective and antioxidant activity of methanolic extract of flowers of Nerium oleander against CCl4-induced liver injury in rats
- Asian Pac. J. Trop. Med., 5 (9) (2012), pp. 677–685
- | | |
- Stuchlik and Kvavadze, 1987
- Subrecent spore-pollen spectra and their relation to recent forest vegetation of Colchis (Western Georgia, USSR)
- Palaeontogr. B., 207 (1987), pp. 133–151 Lfg.1–6
- Tariq, 2009
- Anthelmintic activity of extracts of Artemisia absinthium against ovine nematodes
- Vet. Parasitol., 160 (2009), pp. 83–88
- | | |
- Tushabramishvili et al., 2013
- Human remains from a new Upper Pleistocene sequence in Bondi Cave (Western Georgia)
- J Hum. Evol., 62 (2013), pp. 179–185
- van der Knaap et al., 2010
- Annual pollen traps reveal the complexity of climate on pollen productivity in Europe and Caucasus
- Veg. Hist. Archaeobot., 19 (2010), pp. 285–307
- White, 2008
- Qinghaosu (Artemisinin): the price of success
- Science, 320 (2008), pp. 330–334
- | |
- Willcox et al., 2004
- Artemisia annua as a traditional herbal antimalarial. Traditional medicinal plants and malaria
- CRC press (2004)
- Wichtl, 2002
- Teedrogen und Phytopharmaka
- (4th ed.)Wissenschaftliche Verlagsgesellschaft GmbH, Stuttgart (2002)
- Yesilada, 2002
- Biodiversity in turkish folk medicine
- B. Sener (Ed.), Biodiversity: Biomolecular Aspects of Biodiversity and Innovative Utilization, Kluwer Academic/Plenum Publishers, London, UK (2002), pp. 119–135
- | |
- Zlatović et al., 2014
- Traditional use of the native medicinal plant resource of Mt. Rtanj (Eastern Serbia): ethnobotanical evalution and comparison
- J. Ethnopharmacol., 151 (2014), pp. 704–713
Copyright © 2015 Published by Elsevier Ireland Ltd.
