*3.7. Clusters*

The analysis of the clusters formed by the keywords allows the classification of the different groups into which the research trends are grouped. A first analysis has been made with the documents published between 2009 and 2019 and in two periods, from 2009 to 2014 and from 2015 to 2019. Figure 9 shows the clusters obtained for the period 2009 to 2014, showing seven clusters, which can be distinguished by color, and in Table 6 its main keywords have been collected.

The first of these clusters, in red (1-1), is linked to traditional medicine. This is reflected in the main keywords associated with this cluster: phytotherapy, herbaceous agent, traditional medicine, ethnobotany. Within this cluster, the most cited publications are related to the antioxidant function of plants. This includes the prevention of hyperglycemia hypertension [52], and the prevention of cancer. Of the latter, studies suggest that a reduced risk of cancer is associated with high consumption of vegetables and fruits [53]. Another topic frequently addressed is the antidiabetic properties, as some plants have hypoglycemic properties [34]. It should be remembered that diabetes mellitus is one of the common metabolic disorders, acquiring around 2.8% of the world's population and is expected to double by 2025 [54].

The second cluster, in green (1-2), appears to be the central cluster, and is related to drugs—chemistry. The main keywords are: drug isolation, drug structure, chemistry, drug determination, and molecular structure. Here, the most cited publications are the search for new drugs [55] or in natural antimicrobials for food preservation [56].

The third cluster, in purple (1-3), is focused on in vivo study through studies with laboratory animals, as shown by keywords such as mouse and mice. As it is known that in vivo drug trials are initiated in laboratory animals such as mice, in general studies focused on anti-inflammatory effect [57,58].

The fourth cluster, in yellow (1-4), is engaged in the search for drugs. The main keywords in this regard are unclassified drug and drug screening. Within this cluster, the studies of flavonoids stand out [59]. Flavonoids have been shown to be antioxidant, free radical scavenger, coronary heart disease prevention, hepatoprotective, anti-inflammatory and anticancer, while some flavonoids show possible antiviral activities [60].

**Figure 9.** Network of keywords in medical plants publications: Clusters between 2009–2014.



The fifth cluster, in blue (1-5), is focused on the effectiveness of some drugs, and their experimentation on animals. Some of the most cited publications of this cluster over this period are those focused on genus *Scutellaria* [61], Epimedium (*Berberidaceae*) [62] and Vernonia (*Asteraceae*) [63].

The sixth cluster, in cyan (1-6), is aimed at the effect of extraction solvent/technique on the antioxidant activity. One of the most cited publications in this regard studies the effects on barks of *Azadirachta indica*, *Acacia nilotica*, *Eugenia jambolana*, *Terminalia arjuna*, leaves and roots of *Moringa* *oleifera*, fruit of *Ficus religiosa*, and leaves of *Aloe barbadensis* [64]. Regarding neuroprotection, some publications are the related to genus *Peucedanum* [65] or *Bacopa monnieri* [66]. This cluster is among the clusters of traditional medicine (1-1) and drug efficacy (1-5).

Finally, the seventh orange cluster (1-7) is of small relative importance within this cluster analysis and is focused on malaria. As it is known, malaria is one of the most lethal diseases in the world every year [67]. Malaria causes nearly half a million deaths and was estimated at over 200 million cases, 90 per cent of which occurred in African countries [68]. Of the *Plasmodium* species affecting humans, *Plasmodium falciparum* causes the most deaths, although *Plasmodium vivax* is the most widely spread except in sub-Saharan Africa [69]. On the other hand, this cluster cites *Plasmodium berghei*, which mainly affects mice, and is often used as a model for testing medicines or vaccines [70].

The second period under study, from 2015 to 2019, is shown in Figure 10, where five clusters have been identified, Table 7, as opposed to the previous period which was seven. Now, there is no cluster focusing on malaria. In Figure 10, the colors of the cluster have been unified with those of Figure 9, when the clusters have the same topic as in the previous period.

**Figure 10.** Network of keywords in medical plants publications: Clusters between 2015–2019.


**Table 7.** Main keywords used by the communities detected in the topic in the period 2015–2019.

The first cluster in order of importance (2-1), the red one in Figure 10, can be seen to be that of unclassified drug, which has gone from fourth place (1-4) to first in this last period. In this period, research works include one on the therapeutic potential of spirooxindoles as antiviral agents [71], or the antimicrobial peptides from plants [72].

The second cluster of this last period (2-2), the one in green in Figure 10, is the one assigned to traditional medicine, which has now moved up to second place (1-1) in decreasing order of significance. It seems that this cluster of traditional medicine is now the merging with the drug efficacy cluster of the previous period (1-4). This cluster includes research such as oxidative stress and Parkinson's disease [73].

The cluster from the previous period that was devoted to animals-in vivo study (1-3), we assume is now divided into three new clusters. The first of these would be the third cluster (2-3), blue in Figure 10, which can be considered to be dedicated to cancer. One of the works in this cluster is "Anticancer activity of silver nanoparticles from Panax ginseng fresh leaves in human cancer cells" [74]. Then, the other two are committed to in vivo studies or with animals. The first one seems to be more engaged in vivo study at antidiabetic activity [75,76], would be the cyan-colored cluster 4 (2-4). The other cluster (2-5) involved in testing anti-inflammatory activity, with plants such as Curcumin [77], *Rosmarinus o*ffi*cinalis* [78], would be the purple cluster in Figure 10.
