analgesic plant

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1 Publicado Phytomedicine 8(4): 310-322, 2001 Plants with central analgesic activity R. N. ALMEIDA 1,2 , D. S. NAVARRO 1 and J.M. BARBOSA-FILHO 1 1 Laboratório de Tecnologia Farmacêutica ; 2 Departamento de Fisiologia e Patologia, Universidade Federal da Paraíba, 58051-970, João Pessoa, Caixa Postal 5009, PB, Brazil Summary The present communication constitutes a global review on plant analgesic activity with special emphasis on those found in different parts of the world, including Brazil, which act on the central nervous system. One hundred and sixty six plants belonging to 79 families are reported. Key words: Antinociceptive effect, central analgesic effect, pain, natural products. Introduction Pain is a sensorial modality which in many cases represents the only symptom for the diagnosis of several diseases. It often has a protective function . Throughout history man has used many different forms of therapy for the relief of pain, among them, medicinal herbs are highlighted due to their wide popular use. An example is Papaver somniferum from which morphine was isolated. It is regarded as the prototype of opiate analgesic drugs. In the relief of pain, opiates are generally considered to act on the central nervous system exercising their effects through three opioid receptors (µ, κ and δ), such drugs are especially important for the treatment of chronic pain. Although morphine has reigned for centuries as the king of painkillers, its rule hasn’t been totally benign. There are concerns about its

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Page 1: Analgesic Plant

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Publicado Phytomedicine 8(4): 310-322, 2001

Plants with central analgesic activity

R. N. ALMEIDA1,2, D. S. NAVARRO1 and J.M. BARBOSA-FILHO1

1Laboratório de Tecnologia Farmacêutica ; 2Departamento de Fisiologia e Patologia, Universidade Federal da Paraíba, 58051-970,

João Pessoa, Caixa Postal 5009, PB, Brazil

Summary

The present communication constitutes a global review on plant

analgesic activity with special emphasis on those found in different parts

of the world, including Brazil, which act on the central nervous system.

One hundred and sixty six plants belonging to 79 families are reported.

Key words: Antinociceptive effect, central analgesic effect, pain, natural products.

Introduction

Pain is a sensorial modality

which in many cases represents the

only symptom for the diagnosis of

several diseases. It often has a

protective function . Throughout

history man has used many different

forms of therapy for the relief of pain,

among them, medicinal herbs are

highlighted due to their wide popular

use. An example is Papaver

somniferum from which morphine

was isolated. It is regarded as the

prototype of opiate analgesic drugs.

In the relief of pain, opiates are

generally considered to act on the

central nervous system exercising

their effects through three opioid

receptors (µ, κ and δ), such drugs are

especially important for the treatment

of chronic pain.

Although morphine has reigned

for centuries as the king of

painkillers, its rule hasn’t been totally

benign. There are concerns about its

Page 2: Analgesic Plant

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addictive properties and side effects,

which include respiratory

depression, drowsiness, decreased

gastrointestinal motility, nausea and

several alterations of the endocrine

and autonomic nervous systems.

The objective of the present work

is to classify medicinal plants in

different parts of the world, including

Brazil, which present central

analgesic activity and potentially may

lead to the development of morphine-

like substances devoid of the side-

effects of morphine and related

drugs.

Materials and methods

A systematic analysis study was

carried out through a recent

computer search of data on Natural

Products Alert (NAPRALERT – SM)

and information from several journal

articles, mainly. The plant selection

was based on the effects presented

in specific animal models for

evaluation of analgesic activity,

involving mechanisms controlled by

the central nervous system, such as:

tail flick response to hot water, tail

flick reaction time test, tail immersion

test, hot water induced analgesia,

naloxon reversed analgesic effect,

inhibited substance P- induced

nociceptive response, hot plate

method, hot wire method and tail

pinch method.

Results and discussion

Current world-wide interest in

traditional medicine has led to rapid

development and studies of many

remedies employed by various ethnic

groups of the world. The information

is recorded in alphabetical order of

plant scientific name, family, part

used, place (country where the study

was developed), route of

administration, dose and reference

(Table 1). In this study we have

enumerated 210 medicinal plants

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involving 79 families in which central

analgesic effect was reported, in

recent years from pharmacological

studies carried out in various

research centers in Africa Australia,

Austria, Brazil, China, Congo,

Dominican Republic, Egypt, Ethiopia,

France, India, Indonesia, Iraq, Iran,

Italy, Jamaica, Japan, Jordan, Korea,

Madagascar, Malaysia, Mexico, New

Hebrides, Nigeria, Pakistan, Peru,

Poland, Roumania, Saudi Arabia,

South Africa, South Korea, Spain,

Sudan, Taiwan, Thailand, Tanzania,

Turkey, United Arab Emirates,

U.S.A. and USSR. Most of the

studies were carried out with crude

extract and the intraperitonial route.

The ten principal families in which

such activity has been reported are

Fabaceae (25), Asteraceae (14),

Lamiaceae (13), Apiaceae (10),

Verbenaceae (7), Euphorbiaceae (7),

Piperaceae (6), Ranunculaceae (6),

Rubiaceae (6) and Menispermaceae

(6).

In conclusion, all the 210 plant

species listed appear to be promising

as narcotic analgesic agents with

activity mediated through opiodergic

receptors. However, further

experiments will possibly define this

pharmacological effect. If confirmed

it, may become of importance for

human clinical treatments.

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4 Table 1 – Plants with central analgesic activity

PLANT FAMILY PART USED PLACE ROUTE GIVEN DOSE REFERENCE Abutilon indicum Malvaceae Fixed oil India i.p. 400 and 600 mg/kg Bagi,1985 Acacia ferruginea Fabaceae Stembark India i.p. 50 mg/kg Dhar,1968 Acacia nilotica Fabaceae Pod Saudi Arabia i.g. 500 mg/kg Dafallah,1996 Achillea ageratum Asteraceae Dried aerial parts Spain i.p. 187 and 254 mg/kg Garcia,1997 Acicarpha tribuloides Calyceraceae Dried aerial parts Peru i.g. 50 mcg/kg Capasso,1996 Aconitum carmichaelii Ranunculaceae Root Japan p.o. 0,1 and 0,3 mg/kg Hikino,1979a Tuber i.g. 500 mg/kg Taki,1998 Dried tuber not given 1 and 300 mg/kg Takizawa,1992 Aconitum flavum Ranunculaceae Dried tuber China i.p. not stated Zhu,1981 Aconitum japonicum Ranunculaceae Dried root Japan s.c. 30 mg/kg Hikino,1979b Acorus calamus Araceae Rhizome, root India i.p. not stated Agarwal,1956 Adansonia digitata Bombacaceae Dried fruit pulp Sudan i.g. 400 and 800 mg/kg Rramadan,1994 Afrormosia laxiflora Fabaceae Dried leaf Africa i.g. 0,5 mg/kg Forestieri,1996 Agastache sinense Lamiaceae Dried root Taiwan i.p. 1,3 , 3,8 and 11,4 mg/kg Chow,1976 Ageratum conyzoides Asteraceae Fresh leaf Congo i.p. 50 mg/kg Abena,1993 Leaf essential oil i.g. 2 mg/kg Abena,1996 Albizia lebbek Fabaceae Dried stembark India i.p. 250 mg/kg Gupta,1982 Alhagi maurorum Fabaceae Aerial parts Saudi Arabia i.g. 500 mg/kg Mohsin,1989 Aloe vera Liliaceae Aerial parts Saudi Arabia i.g. 500 mg/kg Mohsin,1989 Dried leaf juice India i.p. 250 mg/kg Gupta,1982 Fresh leaf juice USA s.c. 100 mg/kg Davis,1988 Amelanchier ovalis Rosaceae Dried branches Spain i.g. 750 mg/kg Lasheras,1986 Anacardium occidentale Anacardiaceae Leaf Indonesia i.p. not stated Sardjono,1976 Leaf essential oil India i.p. 300 mg/kg Garg,1984 Anchomanes difforms Araceae Dried rhizome Nigeria g.i. 100 mg/kg Akah,1990 Annona squamosa Annonaceae Defatted seed India i.g. 250 mg/kg Saluja,1994 Apium graveolens Apiaceae Dried seed Jordan i.g. and i.p. 200 mg/kg Atta,1998 Araujia sericifera Asclepiadaceae Dried fruit Spain i.p. 200 mg/kg Bello,1995a Astragalus siculus Fabaceae Dried root Italy i.p. 0,5 mg/kg Bisignano,1994 Baphia nitida Fabaceae Fresh leaf Nigeria i.g. 100 mg/kg Onwukaeme,1991 Berlinia grandiflora Fabaceae Dried bark Nigeria s.c. 10 mg/kg Asuzu,1993 Brassica rapa Brassicaceae Seed Saudi Arabia i.g. 500 mg/kg Mohsin,1989

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Table 1 - Continuation

PLANT FAMILY PART USED PLACE ROUTE GIVEN DOSE REFERENCE Buddleja cordata Buddlejaceae Dried leaf Mexico i.g. 25 and 100 mg/kg Martinez,1996 Bupleurum chinense Apiaceae Dried entire plant China i.p. not stated Wu,1984 Cadia rubra Fabaceae Dried leaf Madagascar not given 300 mg/kg Pieretti,1993 Caesalpinia ferrea Fabaceae Dried fruit Brazil i.p. 10 and 100 mg/kg Carvalho,1996 Calotropis procera Asclepiadaceae Dried aerial parts Saudi Arabia p.o. and i.g. 500 mg/kg Al-Yahya,1985;

Mossa,1991; Mohsin,1989

Cannabis sativa Cannabaceae Entire plant India i.p. 250 mg/kg Dhar,1968 inflorescence Not specified p.o. 53 mg/kg Sofia,1975 Canthium parviflorum Rubiaceae Aerial parts India i.g. not stated Abraham,1986 Caralluma tuberculata Asclepiadaceae Dried entire plant Pakistan i.g. 125 mg/kg Ahmed,1993 Carthamus tinctorius Asteraceae Flowers Saudi Arabia i.g. 500 mg/kg Mohsin,1989 Cedrus deodara Pinaceae Wood essential oil India i.g. 100 mcg/kg Shinde,1999 Celastrus paniculatus Celastraceae Dried flowers Pakistan i.g. 300 mg/kg Ahmad,1994 Centella asiatica Apiaceae Dried entire plant India i.g. 100 mg/kg Sarma,1996 Dried leaf i.g. 20 mg/kg Sakina,1990 Chasmanthera dependens Menispermaceae Fresh leaf Nigeria i.g. 0,2 ml/kg Onabanjo,1991 Chelidonium majus Papaveraceae Entire plant Austria i.p. 9,5 and 28 mg/kg Kleinrok,1992a Dried entire plant Poland i.p. 19 mg/kg Kleinrok,1992b Chrozophora verbascifolia Euphorbiaceae Dried aerial parts Egypt i.p. 500 mg/kg Harraz,1994 Cinnamomum zeylanicum Lauraceae Dried bark Jordan i.p. and i.g. 200 and 400 mg/kg Atta,1998 Citrullus colocynthis Cucurbitaceae Aerial parts Saudi Arabia i.g. 500 mg/kg Mohsin,1989 Clematis chinensis Ranunculaceae Dried root Taiwan i.p. 6 and 12 mg/kg Chow,1976 Cleome viscose Capparidaceae Dried seed Jamaica s.c. 20 mg/kg Singh,1991a Clerodendrum infortunatum Verbenaceae Entire plant India i.p. 500 mg/kg Dhar,1968 Clitoria ternatea Fabaceae Dried aerial parts India i.p. 230 and 460 mg/kg Kulkarni,1988 Cocculus pendulus Menispermaceae Seed Saudi Arabia i.g. 500 mg/kg Mohsin,1989 Commiphora molmol Burseraceae Gun-resin Italy i.g. 10 ml/kg Dolara,1996a Dried gun-resin Africa i.g. 1 mg/kg Dolara,1996b Oleoresin Saudi Arabia g.i. 200 mg/kg Ageel,1985 Cordia francisci Boraginaceae Dried leaf Italy i.g. 5 ml/kg Rapisarda,1992 Freeze-dried leaf i.g. 500 mg/kg Ficarra,1995

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Table 1 - Continuation

PLANT FAMILY PART USED PLACE ROUTE GIVEN DOSE REFERENCE Cordia martinicensis Boraginaceae Freeze-dried leaf Italy i.g. 1 mg/kg Ficarra,1995 Cordia myxa Boraginaceae Leaf Italy i.g. 500 mg/kg Ficarra,1995 Cordia ulmifolia Boraginaceae Freeze-dried leaf Italy i.g. 1 mg/kg Ficarra,1995 Cucumis trigonus Cucurbitaceae Dried fruit India i.p. 2,5 mg/kg Naik,1980 Culcitium canascens Asteraceae Dried aerial parts Peru i.g. 2 mg/kg Okuyama,1994 Curcuma zedoaria Zingiberaceae Dried rhizome Taiwan i.p. 2,2 and 4,4 mg/kg Chow,1976 Cuscuta chinensis Convolvulaceae Dried entire plant India g.i. 1 mg/kg Akbar,1985 Cyathea nilgirensis Cyatheaceae Aerial parts India i.p. 0,25 mg/kg Dhawan,1977 Cymbopogon schoenanthus Poaceae Entire plant Saudi Arabia i.g. 500 mg/kg Mohsin,1989 Cystoseira usneoides Cystoseiraceae Dried thallus Spain i.p. 6,25 mg/kg Vazquez,1995 Datisca cannabina Datiscaceae Dried flowers-seed India i.p. 100 mg/kg Chandhoke,1979 Desmodium canadense Fabaceae Dried entire plant USSR i.p. not stated Batyuk,1987 Dioclea grandiflora Fabaceae Dried rootbark Brazil i.p. 12,5 and 50 mg/kg Batista,1995 Diodia scandens Rubiaceae Dried entire plant Nigeria i.p. 50 mg/kg Akah,1993 Dolichos falcatus Fabaceae Dried root China i.p. 5 mg/kg Huang,1982 Ducrosia ismaelis Apiaceae Essential oil Saudi Arabia i.p. 1 mg/kg Al-Meshal,1986 Egletes viscosa Asteraceae Flower essential oil Brazil i.g. 400 mg/kg Souza,1998 Elaeagnus kologa Elaeagnaceae Aerial parts India i.g. not stated Abraham,1986 Elaeocarpus canitrus Elaeocarpaceae Fruit India i.p. 100 mg/kg Bhattacharya,1975 Eriobotrya bengalensis Rosaceae Aerial parts India i.g. not stated Abraham,1986 Ervatamia coronaria Apocynaceae Dried stem Brazil i.p. 150 mg/kg Henriques,1996 Eryngium foetidum Apiaceae Dried leaf D. Republic i.g. 250 mg/kg Saenz,1997 Eucaluptus camaldulensis Myrtaceae Dried leaf Jordan i.p. 100 mg/kg Lanhers,1991 Euphorbia hirta Euphorbiaceae Dried entire plant New Hebrides i.p. 20 and 141 mg/kg Atta,1998 Fagraea racemosa Loganiaceae Fresh root Malaysia i.g. 3 mg/kg Okuyama,1995 Ficus glomerata Moraceae Dried leaf Africa i.g. 0.5 mg/kg Forestieri,1996 Foeniculum vulgare Apiaceae Dried fruit Saudi Arabia i.g. 500 mg/kg Tanira,1996 Ganoderma lucidum Ganodermataceae Dried fruitbody japan s.c. 100 and 300mg/kg Kasahara,1987 Genista patens Fabaceae Dried leaf-stem Spain i.p. 200 mg/kg Bello,1995b Glaucium flavum Papaveraceae Dried fruit-leaf-root Spain i.p. 400 mg/kg Cabo,1987 Dried leaf-pericarp i.p. 100 mg/kg Cabo,1988

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Table 1 - Continuation PLANT FAMILY PART USED PLACE ROUTE GIVEN DOSE REFERENCE

Harpagophytum procumbens Pedaliaceae Driet root South Africa oral 20 and 200 mg/kg Erods,1978 Hedera rhombea Araliaceae Dried leaf South Korea i.g. 0,5 and 1 mg/kg Lee,1992 Heracleum hemsleyanum Apiaceae Dried root Taiwan oral 11 mg/kg Chow,1976 i.p. 7,8; 11 and 15 mg/kg Chow,1976 Hibiscus sabdariffa Malvaceae Calyx Saudi Arabia i.g. 500 mg/kg Dafallah,1996 Himanthalia helongata Himanthaliaceae Dried thallus Spain i.p 20; 40 and 100 mg/kg Anca,1993a Fresh thallus i.p. 7,5 mg/kg Anca,1990b Himulus lupulus Cannabaceae Strobilus South Korea i.p 100 mg/kg Lee,1993a Dried strobilus i.p. 250 mg/kg Lee,1993b Hypericum calycinum Clusiaceae Dried aerial parts Turkey i.p. 125 and 250 mg/kg Ozturk,1996;

Ozturk,1997 Hypericum perforatum Clusiaceae Dried aerial parts Turkey i.p. 125 and 250 mg/kg Ozturk,1996a;

Ozturk,1997b Inula crithmoides Asteraceae Dried aerial parts Spain i.p. 200 mg/kg Barrachina,1995 Inula viscosa Asteraceae Dried flowering tops Spain i.g. 250 mg/kg Martin,1987 Ipomoea leari Convolvulaceae Deffated seed India i.p. 60 and 90 mg/kg Mujumdar,1983 Irvingia gabonensis Simaroubaceae Dried stembark Nigeria i.p. 500 mg/kg Okolo,1995 Juniperus oxycedrus Cupressaceae Dried leaf-stem Spain i.p. 200 mg/kg Moreno,1998 Laminaria achroleuca Laminariaceae Dried thallus Spain i.p. 100 mg/kg Vazquez,1994 Lantana camara Verbenaceae Dried leaf Africa i.g. 0.5 mg/kg Forestieri,1996 Lawsonia inermis Lyrthraceae Leaf Saudi Arabia i.g. 500 mg/kg Moshsin,1989 Dried leaf Sudan 1 and 500 mg/kg Ali,1995a Seed oil India 1 mg/kg Bagi,1988 Ledebouriella seseloides Apiaceae Entire plant China not given not stated Wang,1991 Dried root i.g. 40 mg/kg Tan,1988 Lepidium sativum Brassicaceae Seed Saudi Arabia i.g. 500 mg/kg Al-Yahya,1994 Leucas aspera Lamiaceae Dried entire plant India s.c 50 and 400 mg/kg Reddy,1993 Leucojum aestivum Amaryllidaceae Dried bulb Turkey i.p 500 mg/kg Cakici,1997 Ligusticum sinense Apiaceae Dried root Taiwan i.p 8,3 mg/kg Chow,1976 Lippia alba Verbenaceae Fresh leaf Brazil i.g. 1 mg/kg Costa,1989 Lippia geminata Verbenaceae Dried leaf Africa i.g. 0,5 mg/kg Forestieri,1996 Luvunga scandens Rutaceae Fruit India i.p 100 mg/kg Mishra,1988 Lycopodium clavatum Lycopodiaceae Dried aerial parts Taiwan i.p 4,1 and 8,2 mg/kg Chow,1976 Lysimachia christinae Primulaceae Dried aerial parts China i.g. 150 and 250 mg/kg Choi,1997 Maesa ramentacea Myrsinaceae Dried aerial parts India i.g. not stated Bhakuni,1988

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Table 1 - Continuation

PLANT FAMILY PART USED PLACE ROUTE GIVEN DOSE REFERENCE Melaleuca elliptica Myrtaceae Fresh aerial part Egypt not given 0,36 mg/kg Aboutabl,1996 Melaleuca styphelioides Myrtaceae Dried leaf Egypt not given 16.8 mg/kg Aboutabl,1996 Mentha piperita Lamiaceae Dried leaf Jordan i.g. and i.p. 400 mg/kg Atta,1998 Mikania cordata Asteraceae Root India i.p. 100 mg/kg Bhattacharya,1986 Morinda citrifolia Rubiaceae Decorticated root France i.p. 800 mg/kg Younos,1990 Morus alba Moraceae Rootbark Japan oral 2 mg/kg Yamatake,1976 Mucuna pruriens Fabaceae Dried fruit trichomes/leaf Africa i.g. 1 and 2 mg/kg Jauk,1993 Myrica nagi Myricaceae Dried stembark India i.p 250 mg/kg Gupta,1982 Myrtus communis Myrtaceae Dried leaf Iraq i.p 150 mg/kg Twaij,1989 Nepeta caesarea Lamiaceae Aerial part essential oil Turkey i.p 0,03 mg/kg Aydin,1998 Nepeta italica Lamiaceae Leaf essential oil Turkey i.p 0,03 mg/kg Aydin,1999 Neurolaena lobata Asteraceae Dried aerial parts Brazil i.g. 100 mg/kg Gracioso,1998 Nigella sativa Ranunculaceae Seed oil India i.g. 1 mg/kg Khanna,1993 Nyctanthes arbor-tristis Verbenaceae Shade dried leaf India i.g. 2 mg/kg Saxena,1987 Ocimum sanctum Lamiaceae Shade dried leaf India i.g. 250 mg/kg Godhwani,1987 Oplopanax elatus Araliaceae Root essential oil China not given not stated Godhwani,1984 Origanum onites Lamiaceae Essential oil Turkey i.p. 0,03 ml/kg Aydin,1996 Paeonia moutan Paeoniaceae Dried root bark South Korea s.c. 200 mg/kg Suzuki,1983 Panax ginseng Araliaceae Leaf Japan i.p. 400 mg/kg Saito,1973 Dried leaf and root Japan i.p. 100 mg/kg Takagi,1977 Dried root South Korea intrathecal 23 mcg/ml Yoon,1998 g.i. 0,25 and 1 mg/kg Hong,1984 not given 300 mg/kg Shin,1997 i.p. 200 mg/kg Bhargava,1990 Panax ginseng Araliaceae Dried root India i.p. 50 mg/kg Mitra,1996 Panax eudoginseng Araliaceae Dried leaf China i.p. 100 mg/kg Lei,1984 Dried root 100, 200 and 400 mg/kg Song,1981 Pancratium maritimum Amaryllidaceae Dried bulb Turkey i.p 1,2 mg/kg Cakici,1997 Paullinia cupana Sapindaceae Dried seed Brazil i.g. 200 mg/kg Vaz,1997 Peganum harmala Zygophyllaceae Dried entire plant Iraq i.p 150 mg/kg Twaij,1989 Persea americana Lauraceae Dried seed Brazil i.p. 80 mg/kg De Oliveira,1975 Photinia serrulata Rosaceae Dried branches Taiwan i.p. 25 mg/kg Chow,1976 Phyla nodiflora Verbenaceae Dried leaf Africa i.g. 0,5 mg/kg Forestieri,1996

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Table 1 - Continuation

PLANT FAMILY PART USED PLACE ROUTE GIVEN DOSE REFERENCE Phyllanthus niruri Euphorbiaceae Dried entire plant Brazil i.g. 0,31/ 504 mg/kg Santos,1995a i.p. 30 mg/kg Santos,1995a Phyllanthus sellowianus Euphorbiaceae Dried entire plant Brazil i.p and i.g. 0,54 and 251 mg/kg Santos,1995b Phyllanthus tenellus Euphorbiaceae Dried entire plant Brazil i.p and i.g. 0,54 and 50 mg/kg Santos,1995b Phyllanthus urinaria Euphorbiaceae Dried entire plant Brazil i.p and i.g. 0,34 and 121 mg/kg Santos,1995b i.p. 10 mg/kg Santos,1995b Pimpinella anisum Apiaceae Dried seed Iraq i.p. 150 mg/kg Twaij,1987 Pinus koraiensis Pinaceae Leaf essential oil China i.p. 0,217 ml/kg Jiang,1988 Piper abutiloides Piperaceae Fresh leaf Brazil i.g. 1 mg/kg Costa,1989 Piper cincinnatoris Piperaceae Fresh leaf Brazil i.g. 1 mg/kg Costa,1989 Piper lindbergii Piperaceae Fresh leaf Brazil i.g. 1 mg/kg Costa,1989 Piper longum Piperaceae Unripe-dried fruit China i.p. 125 mg/kg Pei,1983 Piper methysticum Piperaceae Not specified Australia i.p. 150 and 250 mg/kg Jamieson,1990 Dried rhizome i.p. Jamieson,1989 Dried rhizome-root i.p. Jamieson,1990 Piper umbellatum Piperaceae Dried leaf Congo i.p. 5 ml/kg Bioka,1990 Piscidia erythrina Fabaceae Dried bark USA i.p. 600 mg/kg Aurousseau,1965 Platycodon grandiflorum Campanulaceae Dried root Roumania s.c 2 mg/kg Racz,1982 Polygala cyparissias Polygalaceae Dried leaf-root Brazil i.p and i.g. 3; 50 and 100 mg/kg De Campos,1997 Polypodium vulgare Polypodiaceae Dried root India i.p. 300 mg/kg Mannan,1989 Pongamia pinnata Fabaceae Dried root India i.p. 50 mg/kg Singh,1997 Portulaca grandiflora Portulacaceae Dried aerial parts United Arab Emirates i.p. 400 mg/kg Islam,1998 Portulaca oleracea Portulacaceae Dried aerial parts United Arab Emirates i.p. 400 mg/kg Islam,1998 Prunus spinosa Rosaceae Dried branches Spain i.g. 750 mg/kg Lasheras,1986 Psammosilene tunicoides Caryophyllaceae Dried root China s.c 5 mg/kg Song,1981b Psidium pohlianum Myrtaceae Leaf essential oil Brazil i.g. 40 and 100 mg/kg Santos,1996 Psychotria brachypodia Rubiaceae Dried leaf Brazil i.p. 350 mg/kg Leal,1996 Psychotria colorata Rubiaceae Dried flowers Brazil i.p. 25 mg/kg Amador,1996 Dried leaf i.p. 15,6 and 20 mg/kg Amador,1996;

Elisabetsky,1995 Pterocarpus indicus Fabaceae Aerial parts India i.g. not stated Abraham,1986

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Table 1 - Continuation

PLANT FAMILY PART USED PLACE ROUTE GIVEN DOSE REFERENCE Ptychopetalum olacoides Olacaceae Dried leaf Brazil i.g. 200 mg/kg Vaz,1997 Pycnocomon rutaefolia Dipsacaceae Dried aerial parts Spain i.g. 300 mg/kg Herrera,1989 Quercus infectoria Fabaceae Galls Iran i.p. not stated Dar,1977 Quercus lineata Fabaceae Stembark India i.p. 50 mg/kg Dhar,1968 Randia siamensis Rubiaceae not specified Thailand s.c 300 mg/kg Reanmongkol,

1995 Ranunculus japonicus Ranunculaceae Dried entire plant China i.v. and i.m. 1 and 2,5 mg/kg Cao,1992 Rhamnus procumbens Rhamnaceae Bark India i.p. 200 mg/kg Rao,1983 Rhazya stricta Apocynaceae Dried aerial parts Saudi Arabia i.g. 500 mg/kg Mohsin,1989 Dried leaf United Arab Emirates i.g. 2 and 4 mg/kg Ali,1995b Ricinus communis Euphorbiaceae Dried rootbark India i.p. 250 mg/kg Gupta,1982 Roylea elegans Lamiaceae Dried leaf India i.p. 350 and 500 mg/kg Kumar,1981 Salvia haematodes Lamiaceae Fresh root India i.g. 500 mg/kg Akbar,1989 Santolina chamaecyparissus Asteraceae Dried aerial parts Spain i.p. 60 and 300 mg/kg Giner,1988 Saussurea involucrata Asteraceae Entire plant China i.p. 20 mg/kg Chen,1981 Scabiosa atropurpurea Dipsacaceae Dried flowering tops Spain i.p. 300 mg/kg Requena,1987 Senna italica Fabaceae Dried leaf United Arab Emirates i.g. 0,25 and 0,5 mg/kg Ali,1997 Serjania communis Sapindaceae Fresh stembark Brazil i.g. 1 mg/kg Di Stasi,1988 Sida cordifolia Malvaceae Dried leaf-stem-root India i.p. and i.g. 600 mg/kg Kanth,1999 Sideritis mugronensis Lamiaceae Dried aerial parts Spain i.p. not stated Esplugues,1982

Siphocampylus verticillatus Campanulaceae Dried leaf-stem Brazil i.p. 300 mg/kg Trentin,1997 oral 485 and 640 mg/kg Trentin,1997 Stephania dinklagei Menispermaceae Dried stem Nigeria not given 0,5 ml/kg Akubue,1983 Stefania wightli Menispermaceae Dried entire plant India i.p. 20 mg/kg Nazimuddeen,

1980 Strychnos nux-vomica Loganiaceae Dried seed China i.p. 0,01, 1 and 100 mcg/kg Cai,1996 Synedrella nodiflora Asteraceae Dried entire plant Africa i.g. 0,5 mg/kg Forestieri,1996 Tabebuia chrysotricha Bignoniaceae Dried wood Brazil i.p. 200 mg/kg Grazziotin,1992

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Table 1 - Continuation

PLANT FAMILY PART USED PLACE ROUTE GIVEN DOSE REFERENCE Tabernaemontana pandacaqui Apocynaceae Dried stem Thailand i.p. 0,5 and 250 mg/kg Taesotikul,1989a;1998b

Tamarix milotica Tamaricaceae Pod Saudi Arabia i.g. 500 mg/kg Mohsin,1989 Taraxacum officinale Asteracea Dried leaf Italy i.p. 0,1 mg/kg Tita,1993 Teclea nobilis Rutaceae Dried leaf Ethiopia i.g. 50 mg/kg Mascolo,1988 Tecomella undulata Bignoniaceae Dried entire plant Pakistan i.g. 300 mg/kg Ahmad,1994 Teucrium carthaginense Lamiaceae Dried leaf-stem Spain i.p. 200 mg/kg Bello,1995c Theobroma leiocarpa Sterculiaceae Dried seed Brazil i.p. 80 mg/kg De Oliveira,1975 Thymus vulgaris Lamiaceae Aerial parts S. Arabia i.g. 500 mg/kg Mohsin,1989 Tillandsia usneoides Bromeliaceae Fresh leaf Brazil i.g. 1 mg/kg Costa,1989 Tinospora cordifolia Menispermaceae Not specified India g.i. not stated Pendse,1981 Dried root India i.g. 100 mg/kg Sarma,1996 Tinospora crispa Menispermaceae Dried stem Indonesia i.g. 6,66 ml Teruna,1987 Torresea cearensis Fabaceae Dried stembark Brazil i.g. 200 and 400 mg/kg Leal,1997 Trachelospermum jasminoides Apocynaceae Dried stem Taiwan i.p. 26,8 mg/kg Chow,1976 Trema guineensis Ulmaceae Dried leaf Tanzania i.g. 500 and 1000 mg/kg Barbera,1992 Trianthema portulacastrum Alzoaceae Dried entire plant India i.p. 100 mg/kg Vohora,1983 Tribulus terrestris Zygophyllaceae Dried aerial parts Iraq i.p. 150 mg/kg Twaij,1987 Dried entire plant Saudi Arabia i.p. 500 mg/kg Tariq,1985 Trichilia catigua Meliaceae Dried bark Brazil i.g. 200 mg/kg Vaz,1997 Trigonella anguina Fabaceae Dried entire plant Saudi Arabia i.p. 500 mg/kg Tariq,1985 Trigonella foenum-graecum Fabaceae Dried leaf Iran i.p. 1000 mg/kg Javan,1997 Dried leaf-stem not given not stated Ghafghazi,1985 Typhonium giganteum Araceae Dried rhizome Taiwan i.p. 7,3 and 14,6 mg/kg Chow,1976 Unidentified species Lamiaceae Dried leaf Jordan i.p. 400 mg/kg Atta,1998 Urtica dioica Urticaceae Dried branches Spain i.g. 1200 mg/kg Lasheras,1986 Valeriana jatamansi Valerianaceae Dried leaf India oral 2 mg Shrivastava,1970 Vernonia condensata Asteraceae Dried leaf Brazil i.g. 241 mg/kg Frutuoso,1994 Viola mandshurica Violaceae Dried aerial parts Korea i.g. 5 mg/kg Ko,1987 Vitex negundo Verbenaceae Fruit India oral 3 mg Shrivastava,1970 Zingiber officinale Zingiberaceae Dried rhizome Brazil i.g. 200 mg/kg Vaz,1997 Indonesia i.g. 199,8 mg Latifah,1987 Ziziphus jujuba Rhamnaceae Dried fruit Pakistan i.g. 500 mg/kg Shah,1989

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Prof. Dr. Reinaldo Nóbrega de Almeida, Laboratório de Tecnologia Farmacêutica, Universidade Federal da Paraíba, Caixa Postal 5009, CEP 58051-970, João Pessoa, PB, Brazil Fax: + 55 83 216-7365; e-mail: [email protected]