key: cord-339227-2i9q9c8u authors: Djakpo, Odilon; Yao, Weirong title: Rhus chinensis and Galla Chinensis – folklore to modern evidence: review date: 2010-11-22 journal: Phytother Res DOI: 10.1002/ptr.3215 sha: doc_id: 339227 cord_uid: 2i9q9c8u The species Rhus chinensis Mill. (Anacardiaceae) is an important representative of the genus Rhus, which contains over 250 individual species found in temperate and tropical regions worldwide. Rhus chinensis has long been used by folk medicine practitioners in Asia. Leaves, roots, stem, bark, fruit and particularly the galls on Rhus chinensis leaves, Galla chinensis, are recognized to have preventative and therapeutic effects on different ailments (such as diarrhea, dysentery, rectal and intestinal cancer, diabetes mellitus, sepsis, oral diseases and inflammation). However, it is critical to separate evidence from anecdote. Fortunately, recent scientific research has revealed that Rhus chinensis compounds possess strong antiviral, antibacterial, anticancer, hepatoprotective, antidiarrheal and antioxidant activities. Moreover, compounds isolated from the stem of Rhus chinensis significantly suppressed HIV‐1 activity in vitro. Compounds from this plant were also found to inhibit enamel demineralization in vitro and enhance remineralization of dental enamel with fluoride. This review highlights claims from traditional and tribal medicinal lore and makes a contemporary summary of phytochemical, biological and pharmacological findings on this plant material. It aims to show that the pharmaceutical potential of this plant deserves closer attention. Copyright © 2010 John Wiley & Sons, Ltd. Rhus chinensis belongs to the genus Rhus and the Family Anacardiaceae (Miller et al., 2001) . Commonly called sumac, Rhus consists of approximately 250 individual species of fl owering plants, with six species found (four endemics) in China. Like most sumacs, Rhus chinensis is a dioecious shrub that can reach 8 m in height. It bears odd pinnately compound leaves and creamywhite fl owers. The fruits (drupes) are orange or red in color at maturity and contain one seed (Barkley, 1937; Miller et al., 2001; Tianlu and Barfod, 2008) . The species grows in areas with marginal agricultural capacity, and is widely distributed in temperate, subtropical, and tropical regions, including China, Japan, Malaysia, Taiwan and India (Rayne and Mazza, 2007; Ren et al., 2008) . The species Rhus chinensis has two distinct varieties, Rhus chinensis var. chinensis (syn. Rhus (Tianlu and Barfod, 2008; GRIN; TROPICOS) . Galla chinensis or Galla rhois is the term used to describe the gall caused by the Chinese aphid, Schlech-tendalia chinensis (Bell), on the leaves of Rhus chinensis (Lee et al., 1997) . This gall is widely used as a separate drug. Other species in this genus also produce galls that are considered to have an inferior quality. A plethora of traditional medicine references claim curative power for Rhus chinensis, despite its widespread use, many of these claims of effi cacy were not supported by scientifi c evidence, whether for traditional use validation or for drug development endeavors. Fortunately, recent scientifi c research on Rhus chinensis has revealed promising health benefi ts, including anticancer, antiviral, antimicrobial, antidiarrheal and antiinfl ammatory properties (Yang et al., 2005; Gu et al., 2007; Ahn et al., 1998; Chen et al., 2009; Kim et al., 2005) . In recent years, the Chinese herbal medicine Galla chinensis has been discussed widely as a new alternative for carious disease (Chu et al., 2007) . So far, no comprehensive review has been compiled from the literature encompassing the effi cacy of this plant. Widespread claims of the medicinal effectiveness of various Rhus chinensis tree preparations motivated us to bridge the information gap in this area. Among Rhus species, Rhus chinensis and its gall, Galla chinensis, have a long history of use by indigenous peoples for medicinal care and others. Numerous curative properties are ascribed to different parts of this tree, namely root, bark, stem, leaf, fruit, fl owers, seed and gall ( Table 1 ). The leaves and the root are used as depuratives, stimulating blood circulation. Its decoction is used in the treatment of hemoptysis, infl ammations, laryngitis, snakebite, stomachache and traumatic fractures (Duke and Ayensu, 1985; Kao, 1988; Ouyang et al., 2008) . The ripe fruits of this plant have long been used in Asia to treat dysentery and diarrhea, as well as other gastrointestinal disorders (Kala, 2005; Pradhan and Badola, 2008; Bose et al., 2008) . The fruit produces a sour juice when boiled with water. This juice, when diluted with water or/and mixed with raw eggs, treats diarrhea and dysentery (Pradhan and Badola, 2008) . It is used for the treatment of colic (Chopra et al., 1986) and also as a food preservative (Pradhan and Badola, 2008) . The seed is used in the treatment of cough, dysentery, fever, jaundice, malaria and rheumatism (Duke and Ayensu, 1985; Abbasi et al., 2009) . The gall of Rhus chinensis has long been considered to possess natural medicinal properties with numerous benefi ts . Galla chinensis is used internally for its astringent properties to treat disease such as diarrhea and hemorrhage (Duke and Ayensu, 1985) . It is a frequent ingredient in polyherbal prescriptions for diabetes mellitus (Duke and Ayensu, 1985) . It has hemostatic effects, often used to promote clotting following traumatic injuries and to treat burns (Yeung, 1985) . It is also used to treat rectal and intestinal cancer, prolapse of the rectum, seminal enuresis and hemorrhoids (Yeung, 1985; Gao et al., 2000) . In addition to its antiphlogistic and antiseptic uses for treating diseases such as persistent cough, Galla chinensis also has antiinfl ammatory properties (Tian et al., 2009) . It is also used to counteract ulcers in the mouth and to treat fever and malaria (Duke and Ayensu, 1985; Gao et al., 2000) . Phytochemical studies on Rhus species have been reported earlier and resulted in the characterization of several compound groups such as fl avonoids (Taniguchi et al., 2000; Lee et al., 2005; Lin et al., 2008) , triterpenoids (Kuo, 1991; Parveen, 1991; Lee et al., 2005) , phenolics (Parveen and Khan, 1988; Lee et al., 2005; Ouyang et al., 2008) , tannins (Takechi et al., 1985) and aromatic alkanes (Kuo et al., 1991; Lee et al., 2005; Ouyang et al., 2008) . The galls on Rhus chinensis leaves are rich in gallotannin (50-70%), a type of hydrolysable tannin (Kee and Walter, 1999; Xiao et al., 2000) . Gallotannins from Galla chinensis consist of a central glucose core, which is surrounded by several gallic acid units, and further gallic acid units can be attached through depside bonding of additional galloyl residues. Structures containing 1 to 14 galloyl residues result from such processes, yielding tri-, tetra-, penta-, hepta-and nonagalloylglucose, and others (Xiang et al., 2007; Tian et al., 2009b) . Pentagalloylglucose [1], 3-galloyl-gallic acid and 4-galloyl-gallic acid isomers isolated from Galla chinensis are reported to be the primary bioactive gallotannins, possessing numerous medicinal activities and health benefi ts Sakai et al., 1990; Bhimani et al., 1993; Feldman et al., 2001; . Rhus chinensis is rich in well known phenolic compounds, gallic acid [2] and methyl gallate [3] (Ahn et al., 1998 (Ahn et al., , 2005 Bae et al., 1998; Choi et al., 2009 ). According to Buziashvili et al. (1973) Galla chinensis is composed of nearly 20% gallic acid and 7% methyl gallate. A new benzofuranone, 5-hydroxy-3-(propan-2-ylidene)-7-(3,7,11,15-tetramethylhexade-ca-2,6,10, 11-tetraenyl)-2(3H)-benzofuranone [4], together with 16 known bioactive compounds, including 5-hydroxy-7-(3,7,11,15-tetramethylhexadeca-2,6,10,11-tetraenyl)-2(3H)-benzofuranone [5], 3-oxo-6β-hydroxyolean-12en-28-oic acid [6], 3-oxo-6β-hydroxyolean-18-en-28-oic acid [7] moronic acid [8], betulonic acid [9], gallicin [10], dihydroxytoluene [11] and dimethylcaffi c acid [12] , have been isolated from the root stem of Rhus chinensis (Gu et al., 2007; Wang et al., 2008) . Phenol glycosides and lariciresinol-based ligan glycosides compounds have been shown to be present in the butanol extract of Rhus chinensis root (Ouyang et al., 2007 (Ouyang et al., , 2008 . 6-Pentadecylsalicylic acid, an antithrombotic compound [13] (Kuo, 1991) and fi setin (3,7,3-,4-tetrahydroxyfl avone) [14] an antiinfl ammatory, have also been isolated from the stem of Rhus chinensis. The leaves of this plant are rich in essential oils, with palmitic acid, phytol and n-heptacosane as the major components (Zhu et al., 2007) . The high level of gallotannins along with phenolic compounds, gallic acid and methyl gallate, known antimicrobial agents make Galla chinensis very useful in bacterial control (Wu-Yuan et al., 1988; Ahn et al., 1998; Kang et al., 2008; Tian et al., 2009a Tian et al., , 2009b . Extracts from Galla chinensis inhibited several bacteria such as Bacillus subtilis, B. cereus, Escherichia coli, Enterobacter cloacae, Helicobacter pylori, Klebsiella oxytoca, Lactobacillus casei, L. acidophilus, L. salivarius, Salmonella derby, S. minesota, S. typhimurium, S. enteritidis, Shigella dysenteriae, Staphylococcus aureus, Streptococcus mutans, S. sobrinus, Ureaplasma urealyticum, with the minimal inhibitory concentration (MIC) in the range 0.5-8 mg/ mL (Wu-Yuan et al., 1988 , Bae et al., 1998 Choi II et al., 2002; Kang et al., 2008; Zhu et al., 2008; Choi et al., 2009; Tian et al., 2009a) . Tian et al. (2009b) reported that different gallotannins from Galla chinensis separated according to the number of galloylglucose had signifi cant antibacterial activities on Bacillus cereus and Salmonella typhimurium. Structure activity relationship studies indicated that antibacterial activity was positively correlated with the numbers of galloyl groups and generally, gallotannins with higher molecular weights had strong antibacterial activities (Tian et al., 2009a (Tian et al., , 2009b . A methanol extract of Galla chinensis was shown to have signifi cant growth-inhibitory activity towards harmful intestinal bacteria (Ahn et al., 1994 (Ahn et al., , 1998 . Activity-directed fractionation of the methanol extract of Galla chinensis has led to the isolation of gallic acid and its derivative methyl gallate as the major components involved in the observed antimicrobial activity. It was also reported that methyl gallate and gallic acid from Galla chinensis had inhibitory effects on periodontopathic bacteria (MIC = 1 mg/mL) and signifi cantly reduced the in vitro biofi lm formation of S. mutans (methyl gallate, 1 mg/mL gallic acid, 4 mg/mL, p < 0.05) (Kang et al., 2008) . Anti-HIV activity. In a recent study, different fractions of Rhus chinensis showed potent anti-HIV-1 activity (Wang et al., 2006) . Subsequent anti-HIV guided fractionation of Rhus chinensis led to the isolation of 17 compounds with potent anti-HIV-1 activity (Gu et al., 2007; Wang et al., 2008) . Among those compounds, a new class of benzofuranone-type compounds 5-hydroxy-3-(propan-2-ylidene)-7-(3,7,11,15-tetramethylhexadeca-2,6,10,11-tetraenyl)-2(3H)-benzofuranone [4] and 5-hydroxy-7-(3,7,11,15-tetramethylhexadeca-2,6,10,11-tetraenyl)-2(3H)-benzofuranone [5] were found signifi cantly to suppress HIV-1 replication (Gu et al., 2007) . Compound [4] possessed signifi cant anti-HIV-1 activity with a therapeutic index (TI) of 42.40, whereas compound [5] showed moderate anti-HIV-1 activity with a TI of 3.28 (Gu et al., 2007) . Furthermore, the action mechanisms of the two benzofuranonetype compounds were investigated by Wang et al. (2008) . These authors found that both compounds [4] and [5] inhibited HIV-1 replication in chronically infected H9 cells and may target late-stages of the HIV-1 life cycle. Betulonic acid [9] an analogue of betulinic acid, a well known anti-HIV-1 agent (Kashiwada et al., 1996; Soler et al., 1996) exhibited moderate anti-HIV-1 activity with a TI value of 5.27-8.94 μm (Gu et al., 2007; Wang et al., 2008) . 3-Oxo-6β-hydroxyolean-12-en-28-oic acid [6], 3-oxo-6β-hydroxyolean-18-en-28-oic acid [7] and moronic acid [8] are oleanolic acid-related triterpenes previously reported to have potential anti-HIV-1 activity (Pengsuparp et al., 1994; Soler et al., 1996; Kashiwada et al., 1998) . These compounds showed weak anti-HIV activity with TI values of 4.14, 4.74 and 8.22, respectively (Gu et al., 2007; Wang et al., 2008) . Mengoni et al. (2002) described the anti-HIV and the mechanism of action for oleanolic acid, both of which suggested that oleanolic acid inhibits HIV-1 protease activity in vitro. Gallicins [10], gallic acid derivate-type compounds, have been reported to inhibit HIV-1 integrase . The work of Wang et al. (2008) confi rmed the result in cell lines with a therapeutic index of 5.11. Dihydroxytoluene [11] had the same extent of anti-HIV-1 activity with a TI of 5.34. Wang and coworkers also showed that dimethylcaffi c acid [12] , caffeic acid phenylethyl ester derivate, has potent anti-HIV-1 activity with a TI value of 19.07. These values are relatively low compared with the control AZT (TI > 471883) but the resistance and the adverse side effects to available conventional anti-HIV drugs beg the need of identifi cation and development of additional small-molecule inhibitors that can be used in combination with currently available antiviral agents. In vivo studies performed in mice have shown that the hot-water extract of Rhus chinensis had prophylactic and therapeutic efficacy against herpes simplex virus (HSV) type 1 (HSV-1) (Kurokawa et al., 1993 (Kurokawa et al., , 1995a (Kurokawa et al., , 1995b (Kurokawa et al., , 1997 . This extract was also effective against acyclovir-resistant HSV-1 and HSV type 2 (HSV-2) infections in mice (Kurokawa et al., 1995b) and improved the therapeutic effi cacy of acyclovir in mice infected with HSV-1 (Kurokawa et al., 1995a) . Subsequently, Nakano et al. (1998) also investigated the effi cacy of Rhus chinensis extract in vivo, using a guinea-pig primarily infected intravaginally with HSV-2. Prophylactic oral administration of Rhus chinensis at the dose corresponding to human use signifi cantly reduced the incidence and severity of spontaneous skin lesions compared with latently infected guinea-pigs administered water. When recurrent HSV-2 infection was induced by ultraviolet irradiation 3 months after primary infection, prophylaxis with Rhus chinensis was also signifi cantly effective in reducing the severity of ultraviolet-induced skin lesions. Two terpene compounds, moronic acid [8] and betulonic acid [9], were separated from Rhus chinensis and their subsequent anti-HSV activities were assessed in vitro and in vivo . The effective concentrations of moronic acid and betulonic acid for 50% plaque reduction for HSV-1 were consecutively, 3.9 and 2.6 μg/mL. The therapeutic index of moronic acid (10.3-16.3) was larger than that of betulonic acid O. DJAKPO AND W. YAO (6.2). Oral administration of moronic acid thrice a day to mice infected cutaneously with HSV-1, signifi cantly retarded the development of skin lesions and/or prolonged the mean survival of infected mice without toxicity compared with the control. Moronic acid exerted stronger anti-HSV-1 activity in the brain of HSV-1-infected mice than in the skin, similar to the hotwater extract of Rhus chinensis (Kurokawa et al., 1995a . Anti-HCV and anti-SARS-CoV activities. Screening a library of traditional medicines, Duan et al. (2004) found that the EtOAc extract fraction from Galla chinensis was effi cient in inhibiting the NS3 protease activity of hepatitis carcinoma virus (HCV). 1,2,6-Tri-O-galloyl-βd-glucose, 1,2,3,6-tetra-O-galloyl-β-d-glucose and pentagalloylglucose [1] were identifi ed as the active compounds. Tri-, tetra-and pentagalloylglucose inhibited HCV NS3 protease with IC 50 of 1.89, 0.75 and 1.60 μm, respectively (Duan et al., 2004) . Likewise, tetra-O-galloyl-β-d-glucose isolated from Galla chinensis exhibited prominent inhibition against severe acute respiratory syndrome coronavirus (SARS-CoV) with a 50% effective concentration of 4.5 μm (Yi et al., 2004) . Liu et al. (2003) found that crude aqueous extract of Galla chinensis has the ability to inhibit enamel demineralization in vitro. In another study, Chu et al. (2007) evaluated the effects of compounds from Galla chinensis on the remineralization of initial enamel carious lesions using an in vitro pH cycling model. The group demonstrated the potential of three different fractions of Galla chinensis to affect net rehardening of artifi cial carious lesions under dynamic pH-cyclic conditions. Furthermore, Zou et al. (2008) , using the same protocol, demonstrated the potential of Galla chinensis extract to inhibit the demineralization of initial enamel carious lesions. The chemical compounds of Galla chinensis showed effects and combined effects with fl uoride on enhancing remineralization of dental enamel (Cheng et al., 2008) . At this point, the active compound of Galla chinensis involved in remineralization or demineralization is still unknown. Chu et al. (2007) isolated gallic acid [2] and methyl gallate [3], both of which showed poor activity compared with the crude extract. This result was confi rmed by Cheng et al. (2008) testing the combined effects of Galla chinensis extract or gallic acid with fl uoride on remineralization of artifi cial early enamel caries. They found that both the crude extract of Galla chinensis and gallic acid had synergistic effects with fl uoride on remineralization, but with apparent differing mechanisms. Thus, it seemed that gallic acid was not the only possible active constituent of Galla chinensis to enhance remineralization. Zou et al. (2008) similarly attempted to determine which of the constituent chemical fractions of Galla chinensis conferred a potential anticaries benefi t by comparing the effects of four different fractions of Galla chinensis on demineralization of a bovine enamel model. The crude extract was the most active one, prone to some losses of other active compounds during the separation process. Cai et al. (2004) screened 112 Chinese medicinal plants for antioxidant activity; the results showed that the aqueous extract of Galla chinensis contained the highest antioxidant concentration of 17674 μmol TEAC/100 g. More recently, two similar studies have investigated the antioxidant activity of gallotannins in four different systems, namely 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power, β-carotene linoleic acid system and hydroxyl radical scavenging assays. Tian et al. (2009a) tested the antioxidant activity of gallotannins with different polarities and found that all of the consecutive extracts of Galla chinensis possessed remarkable antioxidant activity. For example, DPPH radical scavenging activity, EC 50 were in the sequence ethyl acetate (1.22 μg/mL) > ether (1.44 μg/mL) > ethanol (1.55 μg/mL) > water (2.11 μg/mL). Generally, all fractions showed better capacity to scavenge free radicals than the controls, BHT and TROLOX. The same results trend was observed with ferric reducing activity. Antioxidant activity increased when the polarity of extracts decreased, suggesting that extracts with weaker polarities contained higher molecular weight tannins, and thus had stronger antioxidant effects. Aware of this fi nding, Tian et al. (2009b) isolated different gallotannins, containing 1-10 galloylglucoses (GG), from Galla chinensis and investigated their antioxidant activities in the above systems. Generally, gallotannins of high degrees of galloylation (5-10 GGs) had stronger antioxidant activities than those of low degrees of galloylation (1-4 GGs).The same conclusion was drawn in earlier work by Yokozawa et al. (1998) . Similarly, methyl gallate and gallic acid have been shown through in vivo and in vitro studies to have antioxidant and radical scavenging activity (Chen and Zhang, 2003; Whang et al., 2005; Madsen and Bertelsen, 1995; Peyrat-Maillard et al., 2000) . It has been demonstrated that pentagalloylglucose possesses antioxidant activity and protects rat neuronal cells from oxidative damage Feldman et al., 2001; Oh et al., 2001; Pan et al., 1999) . Piao et al. (2009) showed that pentagalloylglucose exerts antiapoptotic activity through antioxidant properties. Yang et al. (2005) were the fi rst to report the anticancer activity of Rhus chinensis extract on carcinogenic Cdc25 phosphatases. Several molecules found in Rhus chinensis such as pentagalloylglucose and gallic acid have been shown to have anticancer activity (Bhimani et al., 1993; Madsen and Bertelsen, 1995; Chung et al., 1998; Hu et al., 2008; Kuo et al., 2009) . Pentagalloylglucose has been shown to exhibit in vivo anticancer effects against prostate cancer (Hu et al., 2008; Kuo et al., 2009) , lung cancer (Huh et al., 2005) and sarcoma (Miyamoto et al., 1987) , and in vitro inhibitory effects on the growth and/ or invasion of breast cancer, leukemia, melanoma and liver cancer . Pentagalloylglucose can exert anticancer activity via the inhibition of angiogenesis (Lee et al., 2004; Huh et al., 2005) and invasion of melanoma cells in metastasis (Ho et al., 2002) . In vitro studies showed that pentagalloylglucose signifi cantly inhibited the proliferation and tube formation of bFGF- Phytother. Res. 24: 1739-1747 (2010) treated human umbilical vein endothelial cells (HUVEC) with an IC 50 of 8 μm (Huh et al., 2005) . The result is similar to the in vitro antiangiogenic activity of pentagalloylglucose in VEGF-treated HUVECs (Lee et al., 2004) . Daily injection of 4 and 20 mg/kg of pentagalloylglucose signifi cantly inhibited the growth of the highly angiogenesis-dependent Lewis Lung Cancer allograft by 57% and 91%, respectively (Huh et al., 2005) . Similarly, pentagalloylglucose inhibited the invasion of highly metastatic mouse melanoma B16F10 cells in vitro in a dose-and time-dependent manner, with IC 50 of 15 μm (Ho et al., 2002) . Some other investigations have also demonstrated that derivatives of galloylglucose inhibit not only cancer cell growth (Pan et al., 1999; Hu et al., 2008) but also the invasion of HT1080 human fi brosarcoma cells (Ata et al., 1996) . Several studies of natural hepatoprotective agents have revealed that the extract of Galla chinensis showed promising hepatoprotective activity Tian et al., 2005) . Based on an activity-guided separation scheme An et al. (2005) purifi ed pentagalloylglucose [1] and an equilibrium mixture of 3-galloyl-gallic acid and 4-galloyl-gallic acid isomer from the methanol extract of Galla chinensis and validated their hepatoprotective activity. Pentagalloylglucose [1] and the mixture compounds were found to have marked protective effects on tacrine-induced cytotoxicity in human liver-derived Hep G2 cells with EC 50 values of 70.39 ± 5.4 and 29.51 ± 0.7 μm, respectively, and also inhibited nitrofurantoininduced cytotoxicity in Hep G2 cells at 150.9 ± 6.4 and 23.81 ± 0.5 μm respectively. Furthermore, pentagalloylglucose treatment was able to reduce both hepatocyte necrosis induced by tertbutyl hydroperoxide (4 and 20 μm) and apoptosis induced by glycochenodeoxycholic acid (3.125 to 50 μm) in primary rat hepatocytes (Park et al., 2008) . Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose level due to agents such as α-glucosidase enzyme, which boosts the digestion of carbohydrate to monosaccharides in the process of intestinal absorption. Therefore, Shim et al. (2003) tested the inhibitory effect of an aqueous extract from the gall of Rhus chinensis on α-glucosidase activity in in vitro and in vivo models. Galla chinensis inhibited Bacillus α-glucosidase activity with an IC 50 of 0.9 μg/mL. Its inhibition on α-glucosidase was determined to be noncompetitive and reversible when the enzyme-substrate mixture was simultaneously treated with Galla chinensis. Galla chinensis signifi cantly suppressed the increase of blood glucose level in rats after oral administration of sucrose. These results suggest that Galla chinensis might exert antidiabetic effects by suppressing carbohydrate absorption from the intestine and thereby reducing the postprandial increase in the blood glucose. Likewise, tannic acid, a mixture of gallotannins containing pentagalloylglucose, was found to have a hypo-glycemic effect in patients with type 2 diabetes (Gin et al., 1999) . Aware of this result, Li and coworkers hypothesized that pentagalloylglucose could have antidiabetic activity. Using synthetic pentagalloylglucose in vitro and in an animal assay, it was demonstrated that pentagalloylglucose effectively reduced blood glucose and insulin levels in vitro and in animal models (Li et al., 2005) . Unlike most antidiabetic drugs, pentagalloylglucose may reduce blood glucose without increasing adiposity. The methanol extract of the dried ripe fruit of Rhus chinensis was tested in experimental models of castor oil-induced diarrhea in Swiss albino mice (Tangpu and Yadav, 2004; Bose et al., 2008) . At graded doses, the extract showed remarkable antidiarrheal activity evidenced by an 80.70% reduction in the rate of defecation of control animals at a dose of 600 mg/kg body weight. The extract also reduced intestinal fl uid secretion induced by MgSO 4 and gastrointestinal motility after charcoal meal administration in albino mice (Tangpu and Yadav, 2004) . In the same way, Galla chinensis extracts were found to be effective against enterotoxigenic Escherichia coliinduced diarrhea that produces a heat-labile enterotoxin (LT), which binds to the ganglioside G M1 on the surface of intestinal epithelial cells (Holmgren and Svennerholm, 1992) leading to a massive loss of fl uids and ions from cells (Chen et al., 2009) . Using the patent mouse gut assay in vivo study, Chen et al. (2006) found that Galla chinensis extract exhibited an anti-LT-induced diarrheal effect, with an IC 50 value of 4.7 ± 1.3 mg/mL. Competitive GM1-ELISA assay showed that Galla chinensis suppressed (IC 50 = 0.17 ± 0.02 mg/mL) LTinduced fl uid accumulation by blocking the binding of LTB to G M1 . Thin layer chromatography suggests that the most active fraction that inhibited the binding of LTB to GM1 was composed of mainly phenolics, especially gallic acid which signifi cantly blocked the binding of LTB to G M1 , with an IC 50 value of 10.9 ± 0.3 mm, and suppressed the LT-induced fl uid accumulation in a dose-dependent manner, with an IC 50 value of 25.4 ± 11.6 mm. The work of Kim et al. (2005) showed that Galla chinensis had antiinfl ammatory activity in in vivo and in vitro models. Galla chinensis could control all of the infl ammatory mediators, such as histamine, heparin, lipidderived mediators and various cytokines in the model of immediate-type allergic reaction in a dose-dependent manner through different mechanisms. Latter activityguided fractionation and purifi cation of the EtOAc fractions of the Galla chinensis indicated that the main antiallergic component in Galla chinensis was gallic acid. Fisetin a fl avonoid found in the root of Rhus chinensis (Lin et al., 2008) was also found to down-regulate infl ammatory reactions in stimulated human mast cells . Similarly, pentagalloylglucose has been shown through in vivo and in vitro studies to exercise a strong antiinfl ammatory effect (Oh et al., 2004; Lee et al., 2007 Lee et al., , 2003 Kang et al., 2005) . 6-Pentadecylsalicylic acid has been isolated from airdried stems of Rhus chinensis by bioassay-directed fractionation of the n-hexane extract of the stem (Kuo, 1991) . This compound showed antithrombotic activity at 50 μg/mL using the amidolytic method (Kuo, 1991) . It also prolonged clotting time in a dose-dependent manner in the clotting assay of thrombin-fi brinogen interaction. Rhus chinensis species have long been recognized by folk medicine practitioners as having value and have been revealed to have great medicinal potential, much of which was completely unknown to Western scientists. Over the past few decades, the research efforts on Rhus chinensis extracts indicate that the extracts have promising potential as antiviral, anticarie, antidiarrheal, anticancer, antidiabetic and hepatoprotective agents, among others. Although the work reviewed here substantiated most of the traditional claims on its health effectiveness, more research is required for validation of the uses of this plant. The available information on the different bioactive contents in samples of various parts of this medicinal plant is very limited, both qualitatively and quantitatively. The gall on Rhus chinensis leaves has received much scientifi c attention because of its high gallotannin content and subsequent health potential. However, other parts, such as fruits, leaves, and seeds, can also be investigated based on traditional uses and the fi ndings in other Rhus species. , 5-hydroxy-3-(propan-2-ylidene)-7-(3,7,11,15-tetramethylhexade-ca-2,6,10,11-tetraenyl)-2(3H)-benzofuranone [4], 5-hydroxy-7-(3,7,11,15-tetramethylhexadeca-2,6,10,11-tetraenyl)-2(3H)-benzofuranone [5], 3-oxo-6β-hydroxyolean-12-en-28-oic acid [6], 3-oxo-6β-hydroxyolean-18-en-28-oic acid [ So far, Galla chinensis is the only medicine proven to remineralize a hard tissue like enamel. This is a unique potential for this plant, but the active constituent is still unknown. The mechanistic activity of Rhus chinensis material as prophylactic, therapeutic, anti-HSV, anti-HIV and antidiarrheal medicine needs to be further examined. On the other hand, efforts should also be made to survey other sumac species to determine if these properties are generalized across the Rhus genus. The safety of Rhus chinensis still needs to be rigorously established, since cases of toxicity from intake of gallotannins found in Rhus chinensis have been reported in the literature. Different gallotannins such as tri-, tetra-, hexa-, hepta-, octa-, nona-and decagalloylglucose can reduce blood pressure and blood urea nitrogen, as reported in animal studies in the literature (Feldman et al., 1999; Hofmann et al., 2006; Nishizawa et al., 1983) . Nonetheless, tannins diminish protein digestibility when present in high levels in diets with low protein content and also inhibit human salivary α-amylase, thereby causing potential negative effects on starch digestion and food taste. This needs to be taken in account when testing the effi cacy of Rhus chinensis compounds in human beings by clinical trials for drug use validation. 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