Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2018, Article ID 4930371, 9 pages https://doi.org/10.1155/2018/4930371 Review Article Gallnuts: A Potential Treasure in Anticancer Drug Discovery Jiayu Gao ,1 Xiao Yang ,2 Weiping Yin ,1 and Ming Li3 1 School of Chemical and Pharmaceutical Engineering, Henan University of Scientifc and Technology, Henan, China 2School of Clinical Medicine, Henan University of Scientifc and Technology, Henan, China 3Luoyang Traditional Chinese Medicine Association, Luoyang, Henan, China Correspondence should be addressed to Jiayu Gao; [email protected] Received 8 September 2017; Revised 17 February 2018; Accepted 21 February 2018; Published 29 March 2018 Academic Editor: Chris Zaslawski Copyright © 2018 Jiayu Gao et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Introduction. In the discovery of more potent and selective anticancer drugs, the research continually expands and explores new bioactive metabolites coming from diferent natural sources. Gallnuts are a group of very special natural products formed through parasitic interaction between plants and insects. Tough it has been traditionally used as a source of drugs for the treatment of cancerous diseases in traditional and folk medicinal systems through centuries, the anticancer properties of gallnuts are barely systematically reviewed. Objective. To evidence the traditional uses and phytochemicals and pharmacological mechanisms in anticancer aspects of gallnuts, a literature review was performed. Materials and Methods. Te systematic review approach consisted of searching web-based scientifc databases including PubMed, Web of Science, and Science Direct. Te keywords for searching include gallnut, Galla Chinensis, Rhus chinensis, Rhus potaninii, Rhus punjabensis,nutgall,galloak,Quercus infectoria, Quercus lusitanica, and galla turcica. Two reviewers extracted papers independently to remove the papers unrelated to the anticancer properties of gallnuts. Patents, abstracts, case reports, and abstracts in symposium and congress were excluded. Results and Conclusion. As a result, 14 articles were eligible to be evaluated. It is primarily evident that gallnuts contain a number of bioactive metabolites, which account for anticancer activities. Te phytochemical and pharmacological studies reviewed strongly underpin a fundamental understanding of anticancer properties for gallnuts (Galla Chinensis and Galla Turcica) and support their ongoing clinical uses in China. Te further bioactive compounds screening and evaluation, pharmacological investigation, and clinical trials are expected to progress gallnut-based development to fnally transform the wild medicinal gallnuts to the valuable authorized anticancer drugs. 1. Introduction Gallnuts are a group of very special natural products char- acterized as the plant-insect symbiont. Tey are formed as the Cancer is a generic term for a vast diversity of diseases that pathological excrescences on the young branches or twigs of can afect any organ system throughout the body. Tough plants as a result of the insect attack and deposition of the eggs great eforts have been invested over recent decades, the lead- [3].Historically,gallnutshavebeenusedbybothWestern ing morbidity and mortality rates of human cancer have not and Eastern cultures as a traditional medicine for various dramatically changed [1]. Te development of more efective body disorders, as an astringent in painful hemorrhoids, an anticancer agents thus remains an ongoing challenge. Natural antiphlogistic for infammatory conditions, a treatment for products are the valuable treasury ofering approximately diarrhea and dysentery, and a remedy for toothache and 75% of drugs currently used for cancer treatment [2]. With dental caries [4, 5]. Galla Chinensis and Galla Turcica are the the aim of discovering more potent, more selective, and less two most signifcant gallnuts as a source of medicine widely toxic compounds than today’s drugs, the research of anti- used in diferent countries [5]. cancer agents continually expands and explores new natural Galla Chinensis is formed when the Chinese sumac aphid products coming from diferent sources, among which the Baker (mainly Melaphis chinensis Bell) parasitizes the leaves insect gallnuts could be quoted as an almost wild resource or petioles of the plants of family Anacardiaceae (mainly Rhus rarely systematically studied. chinensis Mill, Rhus potaninii Maxim, and Rhus punjabensis 2 Evidence-Based Complementary and Alternative Medicine (a) (b) Figure 1: Galla Chinensis (a) and Galla Turcica (b). var. sinica (Diels) Rehd. Et Wils) [6]. Galla Chinensis is native record gallnuts medicine (Galla Turcica), as well as their to and mainly distributed in areas of southern provinces of activities in treating diarrhea through eliminating the toxins China,Sumatra,andMalaysia,butitisalsoproducedinsmall and rebuilding the normal gastrointestinal environment [9]. amounts in India, Japan, and Korea [7]. As shown in Figure 1, Te medical uses of the other gallnut, Galla Chinensis, were these gallnuts are typically 4-5 × 1.5 cm in diameter, horned, also frstly recorded to treat the intestinal dysfunction and and reddish-brown in colour, covered with velvety down. Te diarrhea in (Chinese Materia Medica Gleanings) at 741 AD galls are usually harvested between September and October. [10]. Te microenvironment rebalance of digestive system Te medicine Galla Chinensis is the dry and clean gallnuts could thus be considered as one of the major therapeutic afer removal of the larvae [5, 6]. efects of gallnuts, which was claimed to be a signifcant Galla Turcica is formed on the young branches or twigs progress for cancer treatment in the TCM theories. Tis ( of Quercus infectoria Olivier parasitized by the gall wasps, therapeutic efect was further recorded by Oversea Materia ) ( ) ( Cynips gallae-tinctoriae Olivier [8]. Quercus infectoria Olivier Medica , Compendium of materia medica , Fresh ) ( is a small tree or shrub, native to and widely distributed Chinese Materia Medica ,and Truth Chinese Materia ) in the Mediterranean coast countries, mainly Greece and Medica in the following several centuries [13, 19–21]. Turkey,andalsoIranandSyria[5,8].GallaTurcicaistypically Te other therapeutic efect of gallnuts related to cancer 1–2.5 cm in diameter, being almost spherical in shape, with treatment is the pathogen (toxins and heat in TCM the- ( the tuberculated surface on the upper part. Its colour is gray, ories) scavenging. According to Compendium of mate- ) white-brown, olive green, or dark bluish-green (Figure 1). ria medica , one of the most authoritative encyclopedias Te galls of Quercus infectoria Olivier are usually harvested ofTCM,GallaChinensiscouldbeusedintheremedy between August and September [5]. of phlegm, cough, emesia, analgesic, ulcer, and chancre through clearing the exogenous pathogenic heat and toxins [19]. (Oversea Materia Medica), (Ri Hua Zi Materia 2. Records in TCM Encyclopedia Medica), (Amplifcation on Materia Medica Addendum), and (Truth Chinese Materia Medica) also recorded the As the important traditional medicine dates back centuries, antipathogenic activity of gallnuts (Galla Chinensis and the medicinal uses of gallnuts (Galla Chinensis and Galla Galla Turcica) in diferent periods [13, 14, 17, 21]. Terefore, Turcica) have been widely recorded in more than sixteen clas- the accumulated toxins and heat, which were believed as sical Traditional Chinese Medicine (TCM) pharmacopeias the major carcinogenic factors in TCM theories, could be compiled in diferent dynasties of China (Table 1). Tough efectively eliminated under gallnuts treatment. those books were written in numerous obscure TCM ter- Taken together, though there’s no straight conclusion, the minologies, many of recorded uses of gallnuts have been abstracted information from the ancient TCM encyclopedia proved for treating clinical features associated with cancer. has highlighted the potentials of gallnuts as the efective According to the theories of TCM, cancer is caused by anticancer candidates, thus providing an valuable natural the invasion of exogenous pathogenic factors (accumulated resource for further scientifc study. A systematic review was toxinsandheat)andtheimbalanceofendogenousphysical performed with the aims of collecting and analyzing current conditions (air and blood stasis) [36]. Te main therapeutic knowledge of anticancer aspects for gallnuts, which may efects of gallnuts recorded in TCM pharmacopeias are to underpin the fundamental understanding and inspire the clear the heat and toxins and rebalance the pathological gallnuts-sourced drug development. conditions of human body. ( An important medical compendium, Tang Materia 3. Articles Selection Medica) in 659 AD, is the earliest ofcial medical mono- graph compiled by the state authority in the world [37]. Te authors searched numbers of electronic databases, To the best of our knowledge, it is also the frst book to including PubMed, Web of Science, and Science Direct up Evidence-Based Complementary and Alternative Medicine 3 Table 1: Anticancer uses in Chinese classical pharmaceutical books. Year of Gallnuts Book Medical uses Dynasty References publication Galla Turcica Tang Materia Medica Diarrhea Tang 659 AD [9] Galla Chinensis Chinese Materia Medica Gleanings Intestinal dysfunction, diarrhea Tang