Rhus (PROSEA)

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Plant Resources of South-East Asia
Introduction

List of species

Rhus L.

Protologue: Sp. pl. 1: 265 (1753); Gen. pl. ed. 5: 129 (1754).

Family: Anacardiaceae

Chromosome number: x= 13; R. chinensis: 2n= 30, R. succedanea: 2n= 30, R. verniciflua: 2n= 30, 45 (autotriploid)

Major species

Rhus chinensis Miller,
R. succedanea L.

Vernacular names

Sumac, sumach (En).

Origin and geographic distribution

Rhus comprises about 200 species, widely distributed in both hemispheres extending into the subtropics and tropics, abundant in seasonal and dry areas, but surprisingly seldom occurring in Australia; in Malesia some 10 species are found.

Uses

In South-East Asia the galls of R. chinensis are used as an astringent, styptic and a poultice for sores. They are prescribed for haemorrhages, diarrhoea and dysentery, and as an expectorant. Sometimes the fruits are used in diarrhoea. In Papua New Guinea, scrapings of bark or stem of R. taitensis Guillemin (synonym R. simarubaefolia A. Gray) mixed with water is drunk against boils and ulcers. Additionally the bark residue may be placed on boils. R. verniciflua Stokes (synonym R. vernicifera DC.) is a major source of laquer obtained by cutting the bark, and the fruit yields a wax similar to the wax of R. succedanea. Urushiol present in the exudate causes acute dermatitis. In Vietnam it is locally grown intercropped with cinnamon and tea. It may still be cultivated in Malesia for non-commercial purposes. The dried sap is used in traditional Chinese medicine to treat cough in tubercular lung trouble, amenorrhoea and intestinal worms. The leaves are likewise reported to be an anthelmintic and the seeds a haemostatic. Various North American and European Rhus species are used in traditional medicine and are well-known sources of tannin.

R. succedanea is cultivated for the pulpy mesocarp of the fruit yielding a well-known wax, and the stem exudes a highly irritant latex used for laquer. The wax is used as a medium for ointments. R. chinensis is the source of Chinese or Japanese galls known in Europe since the 15th Century, used in tanning and as a blue dye for silk.

Production and international trade

Despite the reported trade of R. chinensis galls from China no information on international trade is available. R. succedanea figures on export lists in India.

Properties

Urushiol is the allergen found in intercellular secretory canals in the stem, leaves and petioles of Rhus. The chemical properties of urushiol have been well studied. The major constituents are pentadec(en)yl catechols, with small amounts of 3-n-heptadec(en)yl catechols. On exposure to the air, the sap turns black due to an oxidation process but still retains its allergenic activity. Urushiol is also found on the surface of the leaves and is thus readily accessible. In contact with the eyes, it may cause swelling of the eyelid and conjunctivitis. If the cornea is involved, pain, photophobia, and blepharospasm may be experienced. Brushing past the foliage with unprotected skin may result in a delayed reaction exhibiting a highly typical linear pattern of vesicular dermatitis. Hypersensitivity may be developed when one comes close to the plants. Urushiol, if allowed to contaminate articles of clothing, animals, tools, etc. may subsequently be transferred to human skin. Even burning the plant material may be hazardous if unburnt particles of the plant, or vaporised urushiol is carried away in the smoke.

The leaves, fruit, and bark of R. succedanea can cause dermatitis, but the sap causes more severe symptoms. Dermatitis develops in workers handling fabrics waterproofed with the wax. This plant is the commonest cause of "poison ivy dermatitis" in Australia. Laccol, isolated from this species, was identified as a 3-heptadec(en)yl catechol.

R. verniciflua and its lacquer can give rise to dermatitis at all stages from the initial collection of the latex to the final application of the lacquer, and even, it appears, a thousand years later. The clinical features are almost infinitely variable, according to the mode and sites of contact, and the degree of sensitivity. Repeated contact may lead to hypersensitization. The lacquer contains 3-pentadec(en)yl catechols. Urushiol constitutes 35-70% of Chinese lacquer, and a somewhat greater proportion of Japanese lacquer. Sensitivity to R. verniciflua is specific with no cross-sensitivity to R. succedanea or R. radicans L.(poison ivy).

The first symptom is intense pruritus; papules soon appear, often in a linear pattern in the case of poison ivy contact, and these evolve into vesicles or bullae. Any and all parts of the body may be affected in severe cases, the allergenic material being easily carried by the fingers to sites remote from the points of initial contact. The allergenic material is not, however, present in the vesicle fluid. Areas of thicker skin are less susceptible. Except in regions well protected by hair, oedema may be considerable, and particularly so on the eyelids and male genitalia. The evolution of the eruption occurs in crops, affecting first the sites where most allergen has been absorbed, and then successively the less heavily contaminated sites or sites of thicker skin. The dermatitis commonly reaches its full extent after 48 hours. Healing occurs within 2-3 weeks unless there is re-exposure to the offending allergen. Scarring does not occur unless secondary infection has been introduced.

Experiments in guinea-pigs showed that urushiol can induce delayed type hypersensitivity. The activity depends on the nature of the ring substituents. Catechol and 3-n-alkyl catechols were equally effective in inducing sensitivity, but the degree of sensitivity as well as cross-reactivity depended upon the length of the alkyl chain. Dermal toxicity was unrelated to sensitising capacity. Further studies emphasised the importance of the alkyl chain in determining antigenic specificity and non-reciprocal cross-reactivity.

Urushiol isolated from the sap of R. verniciflua exhibited cytotoxicity against L1210 (mouse leukaemia cells), PC-9 (human lung adenocarcinoma cells), A427 (human lung adenocarcinoma cells) and KATO III (human stomach adenocarcinoma cells). Urushiol was most active against A427 cells, but was more potent than tetraplatin against KATO III cells. Hinokiflavone isolated from R. succedanea showed cytotoxic activity. Comparison of cytotoxic activity of hinokiflavone and related biflavonoid indicated that ether linkage between two units of apigenin is structurally required.

R. chinensis has been shown to exhibit anti-herpes simplex virus (HSV) activity and potentiate the anti-HSV activity of acyclovir in vitro and in vivo. This hot water extract (obtained from a commercial source in Japan) was examined for its suppressive efficacy on recurrent genital infection in guinea-pigs which were primarily infected intravaginally with HSV type 2 (HSV-2). Prophylactic oral administration of R. chinensis, at the dose corresponding to human use, significantly reduced the incidence, severity and/or frequency of spontaneous and severe skin lesions as compared with latently infected guinea-pigs administered with water. This prophylactic efficacy was confirmed by the crossover administration, for more than 2 months, of R. chinensis and water to the infected guinea-pigs. Toxicity, such as weight loss, from R. chinensis administration was not observed. When recurrent HSV-2 disease was induced by ultraviolet irradiation 3 months after primary infection, the prophylaxis with R. chinensis was also significantly effective in reducing the severity of ultraviolet-induced skin lesions. Thus, prophylaxis of recurrent genital HSV-2 infection with R. chinensis may preserve the efficacy of acyclovir by reducing both the use of acyclovir and the appearance of acyclovir-resistant viruses. R. chinensis extracts show therapeutic anti-herpes simplex virus type 1 (HSV-1) activity. In combination with acyclovir, the standard medication, the effect in mice was stronger, compared with both acyclovir and the herbal extract alone.

R. chinensis exhibits oral therapeutic anti-herpes simplex virus (HSV) activity in mice. Two major anti-HSV compounds, moronic acid and betulonic acid, were isolated from the herbal extract using ethyl acetate at pH 10. Moronic acid was quantitatively the major anti-HSV compound in the ethyl acetate-soluble fraction. The effective concentrations of moronic acid and betulonic acid for 50% plaque reduction of wild-type HSV type 1 (HSV-1) were 3.9 and 2.6 μg/ml, respectively. The therapeutic index of moronic acid (10.3-16.3) was larger than that of betulonic acid (6.2). Susceptibility of acyclovir-phosphonoacetic acid-resistant HSV-1, thymidine kinase-deficient HSV-1, and wild-type HSV type 2 to moronic acid was similar to that of the wild-type HSV-1. When this compound was administered orally to mice infected cutaneously with HSV-1 three times daily, it significantly retarded the development of skin lesions and/or prolonged the mean survival times of infected mice without toxicity compared with the control. Moronic acid furthermore suppressed virus yields in the brain more efficiently than those in the skin. This was consistent with the prolongation of mean survival times. A hot water extract of R. chinensis inhibited replication of human and murine cytomaegalovirus in vitro.

A methanol extract of R. chinensis shows strong in vitro inhibitory activity against Clostridium perfringens under anaerobic conditions.

Methyl gallate (MG) and gallic acid (GA) isolated from galls of R. chinensis show growth inhibitory activity against intestinal bacteria in the impregnated paper disk method. At 10 mg/disk, MG and GA inhibited the growth of Bacteroides fragilis, Clostridium perfringens, C. paraputrificum, Escherichia coli, Eubacterium limosum and Staphylococcus aureus. MG was inactive against Bifidobacterium adolescentis and B. longum. The growth of Bifidobacterium animalis, B. bifidum, B. breve, B. infantis, B. thermophilum, Lactobacillus acidophilus, L. plantarum and Streptococcus faecalis was slightly affected by MG. GA did not adversely affect the growth of bifidobacteria or lactobacilli. At 5 mg/disk, MG significantly inhibited the growth of C. perfringens and C. paraputrificum but did not affect the growth of the bifidobacteria or lactobacilli. At 1 mg/disk, MG inhibited the growth of C. perfringens alone.

Bioassay-directed fractionation of the n-hexane extract of the stem of R. chinensis has led to the isolation of 6-pentadecylsalicylic acid. It showed antithrombin activity at 50 μg/ml in the amidolytic method. It also prolonged the clotting time in a dose-dependent manner in the clotting assay of thrombin-fibrinogen interaction. The extract inhibited cyclooxygenase and lipoxygenase which are the important enzymes involved in the platelet aggregation process. Therefore it may be useful in treating thrombosis and arteriosclerosis. The ether-soluble fraction of R. chinensis was active at only 10 mg/l in arachidonic acid metabolism in rabbit platelets.

A crude methanol extract of R. chinensis was screened for its effect in immunoglobulin A nephropathy, by testing its effect on human mesangial cell proliferation. The extract inhibited human cell proliferation activated by interleukin-1β (IL-1β) and IL-6 at 31 μg/ml, and decreased IL-1β and tumour necrosis factor-αproduction. Moreover, IL-1β mRNA expression was also inhibited by the extract.

Extract of R. chinensis galls (SG) and its major constituent gallic acid (GA) were administered intraperitoneally (i.p.) or orally (p.o.) to rats with CCl₄-induced hepatitis. Both substances significantly prevented the progression of acute liver injury with both p.o. and i.p. administration. It was suggested that the mechanism for this prevention might be due mainly to the protective effect of these substances on cell membranes rather than O₂ radical-scavenging activities.

The leaves of R. succedanea contain 8-10% tannins as a possible good source for commercial tanning.

Robustaflavone, a naturally occurring biflavanoid isolated from the seed kernel extract of R. succedanea, was found to be a potent in vitro inhibitor of hepatitis B, with an effective concentration (EC₅₀) of 0.25 μM and an in vitro selectivity index (IC₅₀/EC₉₀) of 153. Further studies suggested that inhibition of HBV DNA polymerase is the mechanism of action. The methanol extract of R. chinensis showed growth inhibition effect in Brassica rapa L. at a concentration of 500 ppm.

Biflavonoids obtained from the seed kernel of R. succedanea, such as amentoflavone, agathisflavone, robustaflavone, hinokiflavone, rhusflavanone and succedaneaflavone and their acetates rhusflavanone hexaacetate and succedaneaflavone hexaacetate were evaluated for their antiviral activities. The inhibitory activities against a number of viruses including respiratory viruses (influenza A, influenza B, respiratory syncytial, parainfluenza type 3, adenovirus type 5 and measles) and herpes viruses (HSV-1, HSV-2, HCMV and VZV) were investigated in various human and animal cell lines. The results indicated that robustaflavone exhibited strong inhibitory effects against influenza A and influenza B viruses with EC₅₀ values of 2.0 μg/ml and 0.2 μg/ml, respectively, and selectivity index values (SI) of 16 and 454, respectively. Amentoflavone and agathisflavone also demonstrated significant activity against influenza A and B viruses. Amentoflavone and robustaflavone exhibited moderate anti-HSV-1 and anti-HSV-2 activities with EC₅₀ values of 18 μg/ml (HSV-1) and 48 μg/ml (HSV-2), and SI values of > 5.6 (HSV-1) and > 2.1 (HSV-2) for amentoflavone; EC₅₀ values of 8.6 μg/ml (HSV-1) and 8.5 μg/ml (HSV-2), and SI values of > 11.6 (HSV-1) and > 11.8 (HSV-2) for robustaflavone. Rhusflavanone demonstrated inhibitory activities against influenza B, measles and HSV-2 viruses with SI values of 9.3, 8 and > 6.4, respectively. Succedaneaflavanone exhibited inhibitory activities against influenza B virus and VZV with SI values of 15 and < 3.0, respectively.

Robustoflavone and hinokiflavone isolated from the seeds of R. succedanea demonstrated activity against HIV-1 reverse transcriptase in primary human lymphocytes at an IC₅₀ value of 65 μM, amentoflavone and agathisflavone were moderately active at an IC₅₀ value of 119 μM and 100 μM, respectively.

Description

Erect or scandent shrubs, trees or lianas, sometimes hemi-epiphytic, mostly deciduous.
Leaves spirally arranged, imparipinnate, trifoliolate, unifoliolate, rarely simple; leaflets usually (sub)opposite, entire, rarely crenate-dentate, with or without domatia or a spot-like group of papillae or glands; petiolate; stipules absent.
Inflorescence paniculate, rarely racemose and few-flowered, (pseudo-)terminal or axillary.
Flowers unisexual or bisexual, 5-merous; calyx 5-lobed; petals 5; stamens 5; ovary superior, 1-celled, disk present.
Fruit a drupe, 1-celled.
Seed with testa adnate or free; embryo straight, cotyledons free, flat.

Growth and development

The galls on the leaf of R. chinensis are globular or cone-shaped, but as they develop, they become branched or produce horn-like protuberances in each of which is a cavity occupied by the insects. The galls are at first greenish yellow, but later turn dark green with patches of red, they are covered with a dense velvety fur. On reaching maturity on the tree, the galls split open and the insects escape. R. chinensis flowers from July-October, and fruits mature in September-November. R. succedanea flowers in April and fruits mature in August. R. taitiensis flowers and fruits almost throughout the year.

Other botanical information

Here Rhus is considered in a broad sense. Some authors prefer to separate e.g. Toxicodendron, which is to be distinguished by fruits which are not glandular pubescent, by significantly smaller pollen grains and by the presence of a toxic latex.

Ecology

In South-East Asia, Rhus is usually found in primary or montane forest, sometimes in savanna, in mossy and inundated forest, or in secondary vegetation from sea-level up to 2400 m altitude.

Propagation and planting

Most species of Rhus are propagated by seed. R. verniciflua is easily propagated by root cuttings. Soaking the seeds in hot water for 30 seconds significantly increases germination of R. chinensis .

In vitro production of active compounds

Adventitious root cultures of R. chinensis produce large amounts of galloylglucoses (gallotannins) and an anthocyanidin, riccionidin A, found also in liverworts. Production of both galloylglucoses and riccionidin A in the adventitious root culture system is suppressed by light. The root culture showed the highest productivity for those secondary metabolites in a modified Linsmaier-Skoog (LS) liquid medium containing 30 mM NH₄⁺ and 30 mM NO₃^- as N sources in the presence of 10^-6M indole acetic acid.

Husbandry

Casing the gall-forming aphids (Schlechtendalia chinensis) in bags on the tree at the appropriate time increases the number of leaves with galls in R. chinensis. Artificial infestation in spring with aphids that have overwintered in an insectary likewise increases gall yield. In Japan, R. vernicifera is cultivated as coppice, varnish is obtained by making incisions in 3-year-old stems, and when depleted the stems are removed. Important in more temperate China and Japan, it has been tried in plantations in South-East Asia, but failed there.

Diseases and pests

R. succedanea may suffer locally from Fusarium spp. causing wilt.

Harvesting

Galls of R. chinensis are harvested before they split open and the aphids escape. Fruits are harvested when mature. In Japan, fruits of R. succedanea for commercial extraction of wax are harvested before they are fully ripe and stored in straw to mature. In China, however, they are harvested when fully mature.

Yield

Dried galls of R. chinensis contain 50-80% tannin, principally in the form of gallotannic acid.

Handling after harvest

The galls of R. chinensis are immersed in boiling water to kill the insects, and subsequently dried in the sun. Fruits of R. chinensis are eaten fresh, and as such used medicinally. In China, the wax of R. succedanea is extracted by steaming the crushed fruit and running off the melted fat. In Japan, the fruits are crushed, the seeds removed, and the pulp is steamed and pressed for wax.

Genetic resources and breeding

All Rhus species described here have a large area of distribution, either naturally or as a result of cultivation, and do not seem to be at risk of genetic erosion. There are no known breeding programmes of Rhus for medicinal purposes.

Prospects

The potential for cultivation of R. chinensis in other South-East Asian countries appears limited, as traditionally used galls are not produced in the absence of the aphid species. The biological activities of isolated compounds, especially the flavones and moronic acid in the field of virus inhibition are very interesting, and therefore merit further research in order to evaluate their potential in development of future anti-virals.

Literature

Ahn, Y.J., Lee, C.O., Kweon, J.H., Ahn, J.W. & Park, J.H., 1998. Growth-inhibitory effects of Galla Rhois-derived tannins on intestinal bacteria. Journal of Applied Microbiology 84(3): 439-443.
Ding Hou, 1978. Rhus. In: van Steenis, C.G.G.J. (Editor): Flora Malesiana. Series 1, Vol. 8. Sijthoff & Noordhoff International Publishers, Alphen aan den Rijn, the Netherlands. pp. 534-541.
Kanai, S. & Okano, H., 1998. Mechanism of the protective effects of sumac gall extract and gallic acid on the progression of CCl4-induced acute liver injury in rats. American Journal of Chinese Medicine 26(3/4): 333-341.
Kurokawa, M., Basnet, P., Ohsugi, M., Hozumi, T., Kadota, S., Namba, T., Kawana, T. & Shiraki, K., 1999. Anti-herpes simplex virus activity of moronic acid purified from Rhus javanica in vitro and in vivo. Journal of Pharmacology and Experimental Therapeutics 289(1): 72-78.
Lin, Y.M., Flavin, M.T., Schure, R., Chen, F.C., Sidwell, R., Barnard, D.L., Huffman, J.H., Kern, E.R., Lin, Y.M. & Chen, F.C., 1999. Antiviral activities of biflavonoids. Planta Medica 65(2): 120-125.
Nakano, M., Kurokawa, M., Hozumi, T., Saito, A., Ida, M., Morohashi, M., Namba, T., Kawana, T. & Shiraki, K., 1998. Suppression of recurrent genital herpes simplex virus type 2 infection by Rhus javanica in guinea pigs. Antiviral Research 39(1): 25-33.

Selection of species

Authors

S. Aggarwal