Chemical and Biological Research on Herbal Medicines Rich in Xanthones

Xanthones, as some of the most active components and widely distributed in various herb medicines, have drawn more and more attention in recent years. So far, 168 species of herbal plants belong to 58 genera, 24 families have been reported to contain xanthones. Among them, Calophyllum, Cratoxylum, Cudrania, Garcinia, Gentiana, Hypericum and Swertia genera are plant resources with great development prospect. This paper summarizes the plant resources, bioactivity and the structure-activity relationships (SARs) of xanthones from references published over the last few decades, which may be useful for new drug research and development on xanthones.


Introdution
Xanthones (IUPAC name 9H-xanthen-9-one) are a kind of phenolic acid with a three-ring skeleton, widely distributed in herbal medicines. These constituents display a vast range of bioactitivies, including anticancer, anti-oxidative, antimicrobial, antidiabetic, antiviral, and anti-inflammatory effects. So far, at least 515 natural xanthones from 20 families of higher plants (122 species in 44 genera) have been summarized in a few reviews [1][2][3]. These reviews were limited to xanthones with anticancer and anti-inflammatory activities [4]. Their structure-activity relationships (SARs) were also not mentioned.
Over the past few decades, xanthones have become an important resource for drug development. For example, gambogic acid, a prenyl xanthone isolated from Garcinia hanburyi (Clusiaceae), exhibited remarkable apoptosis, cell proliferation and tumor angiogenesis bioactivities, along with anti-oxidant, and anti-inflammatory activities [5,6] and synergistic anticancer activity [7,8]. A phase II clinical trial using gambogic acid in combination with anticancer drugs was carried out in China [9]. Besides gambogic acid mentioned above, mangosteen, another of the most well-known xanthones, has been used as a dietary supplement to improve immune function, decrease serum C-reactive protein levels and increase the ratio of T helper cells [10].

Bioactivities of Xanthones
Recently, some xanthones have been reported to be useful in the treatment of cancer, oxidation, microbial infection, diabetes, inflammation, virus infection et al. Target-based and structure-based activity evaluation has revealed that xanthones are good source of medicine for the treatment of various type of disease. In this part, we summarized pharmacological activities and SARs result of xanthones.

Bioactivities of Xanthones
Recently, some xanthones have been reported to be useful in the treatment of cancer, oxidation, microbial infection, diabetes, inflammation, virus infection et al. Target-based and structure-based activity evaluation has revealed that xanthones are good source of medicine for the treatment of various type of disease. In this part, we summarized pharmacological activities and SARs result of xanthones.
Although some xanthones showed significant inhibitory effects on cancer cell growth in vitro, the in vivo validatation report is rare, which limited their potential for development into new drug for anticancer.  (Figure 3) were gained from G. cylindrocarpa [180], along with the increase of methoxy, the anti-proliferative potency against oral epidermoid KB cell line (IC50: 2 (Figure 4) [181]. Moreover, gentiakochianin (49) and gentiacaulein (50) from G. kochiana [106] were also proved to promote cell cycle arrest in G2/M and G0/G1 phases in U251 human glioma cell line. Muchimangin B (51) [172] and allanxanthone A (52) (Figure 4) [23] inhibited the growth of pancreatic cancer (PANC-1), multiple myeloma (RPMI8226) and gastric cancer (BGC-823) cell lines. The SARs of above xanthones were not discussed for limitation on test sample number.
Although some xanthones showed significant inhibitory effects on cancer cell growth in vitro, the in vivo validatation report is rare, which limited their potential for development into new drug for anticancer.

Free Radical Scavenging Activity
Free radicals are defined as atoms with one unpaired electron, which can be formed through natural physiological processes. Overproduction of free radicals can accelerate the progression of cancer, cardiovascular disease, and age-related diseases.

Free Radical Scavenging Activity
Free radicals are defined as atoms with one unpaired electron, which can be formed through natural physiological processes. Overproduction of free radicals can accelerate the progression of cancer, cardiovascular disease, and age-related diseases.

Conclusions
As a class of secondary metabolites obtained from a number of herbal medicines, xanthones are playing more and more important roles in new drug research and development. The pharmacokinetics and toxicity (PK/tox) properties of xanthones, as part of the most crucial preclinical studies, have proved that xanthones are promising drug candidates owing to their high efficacy and low toxicity [186,187].
In this paper, we have summarized the plant sources, bioactivity and the SARs of xanthones from literature published over the last few decades. As a result, 168 species of herbal medicine plants belonging to 58 genera, and 24 families were found to be enriched in xanthones. Among them, the Calophyllum, Cratoxylum, Cudrania, Garcinia, Gentiana, Hypericum and Swertia genera are the plant resource with the most development prospect. Xanthones display multiple bioactivities, which may be useful for new drug development for cancer, inflammation, bacterial, fungal and viral infection, diabetes, and so on.