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Anti-inflammatory activity of alkaloids: A twenty-century review

Article  in  Revista Brasileira de Farmacognosia · March 2006


DOI: 10.1590/S0102-695X2006000100020

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Revista Brasileira de Farmacognosia
Brazilian Journal of Pharmacognosy
Received 09/29/05. Accepted 01/25/06 16(1): 109-139, Jan./Mar. 2006

Anti-inflammatory activity of alkaloids:


A twenty-century review

Revisão
José M. Barbosa-Filho1*, Márcia R. Piuvezam1, Marcelo D. Moura1, Marcelo S. Silva1, Karla
V. Batista Lima1, Emídio V. Leitão da-Cunha1,2, Ivana M. Fechine3, Orlando S. Takemura4,
1
Laboratório de Tecnologia Farmacêutica “Delby Fernandes de Medeiros”, Universidade Federal da Paraíba,
Caixa Postal 5009, 58051-970, João Pessoa, PB, Brazil,
2
Departamento de Farmácia, Universidade Estadual da Paraíba, CCBN, 58100-000,
Campina Grande, PB, Brasil,
3
Departamento de Química, Universidade Estadual da Paraíba, CCEN, 58100-000,
Campina Grande, PB, Brasil,
4
Laboratorio de Farmacologia, Universidade Paranaense, Caixa-Postal 224,
Centro, 87502-210, Umuarama, PR, Brasil

RESUMO: “Atividade anti-inflamatória de alkalóides: Uma revisão do século XX”. Muitas


substâncias que interferem na resposta inflamatória têm sido isoladas de plantas. Esta revisão mostra
alguns alcalóides de origem vegetal que no período de 1907-2000 foram avaliados quanto a uma
possível atividade anti-inflamatória. Os alcalóides foram classificados em subgrupos de acordo
com suas estruturas químicas e os dados farmacológicos foram obtidos de diferentes modelos
experimentais. Dos 171 alcalóides avaliados, 137 apresentaram atividade anti-inflamatória, e, entre
eles, os alcalóides do tipo isoquinolínicos foram os mais estudados. O modelo de edema de pata
induzido por carragenina foi o mais empregado para avaliação da atividade anti-inflamatória. Nesta
revisão 174 referências foram consultadas.

Unitermos: Alcalóides, atividade anti-inflamatória, inflamação, modelos experimentais.

ABSTRACT: Many substances which interfere with the inflammatory response have been isolated
from plants. This review shows some alkaloids of vegetal origin which in the period of 1907 to
2000 were evaluated regarding a possible anti-inflammatory activity. The alkaloids were classified
in sub-groups in accordance with their chemical structures and the pharmacological data were
obtained from different experimental models. Of the 171 evaluated alkaloids, 137 presented
anti-inflammatory activity, and among those, the isoquinoline type was the most studied. The
Carrageenin-induced paw edema was the most used model for evaluating the anti-inflammatory
activity. In this review, 174 references were cited.

Keywords: Alkaloids, anti-inflammatory activity, inflammation, experimental models.

INTRODUCTION The main pathophysiological pathways for drug


targeting at present are: arachidonic acid metabolism;
Inflammation can be defined as a generalized, the complement cascade; phagocytosis and other cell
nonspecific but beneficial response of tissues to injury. functions; auto-immune processes; protein kinase C and
It comprises a complex array of adaptive responses to others enzymes involved in second messenger systems
tissue injury which are both local and systemic. The (Willianson, 1996). Early inflammation changes in
local responses result in recruitment of phagocytic cells damaged tissues are now known to involve the release
and removal of endogenous or foreign material. The of various biologically active materials from polymorph
systemic responses may alter the ‘milieu interior’ to nuclear leukocytes, lysossomal enzymes and others.
allow these processes to occur more efficiently (Denko, The vascular effects are primarily mediated by kinins,
1992; Henson; Murphy, 1989). The cellular processes prostaglandins and vaso-active amines (e.g. histamine,
of inflammation fall into four major groups: changes released by mast cells), which cause increased vascular
in blood flow caused by changes in smooth muscle cell permeability leading to plasma exudation.
function causing vasodilatation, alterations in vascular The inflammatory process involves a complex
permeability engendered by cytoskeletal contraction in interplay between cells of the blood, the blood vessels
endothelial cells, migration of phagocytic leukocytes to themselves and the cells of the involved tissue. The
the site of inflammation, and phagocytosis (Denko, 1992; process can be seen as a coordinated response of a large
Evans; Whicher, 1992). number of cells to an initial stimulus (Henson; Murphy,

ISSN 0102-695X 109


* E-mail address: jbarbosa@ltf.ufpb.br, Tel/Fax: + 55-83-32167364
José M. Barbosa-Filho, Márcia R. Piuvezam, Marcelo D. Moura, et al.

1989). products and 60–80% of antibacterial and anticancer


The immigrating cells themselves exert drugs were also derived from natural products (Cragg et
little effect by their presence alone, but initiate all the al., 1997). Plants offer a vast source of compounds that
complex reaction of inflammation as a consequence of present different effects in human.
the materials that they secrete or release to the extra The alkaloids comprise the largest single class
cellular environment. Such materials include molecules of secondary plant substances. They have a remarkable
that exacerbate the response by attracting further range of pharmacological activity. The term alkaloids
inflammatory cells, inhibitors that serve to reduce the generally include those basic substances that contain one
severity of the reactions, histotoxic agents such as or more nitrogen atoms, usually in combination as part of
proteases, oxygen metabolites and cations, as well as a ciclic system (Harborne, 1991). They are often toxic to
signals to the surrounding inflammatory and tissue cells man and many have dramatic physiological activities.
to implement some or all of the complex reactions which Different approaches used to analyze the
they are capable (Henson; Murphy, 1989). anti-inflammatory potential of plant and plant-derived
Uncontrolled inflammation is undesirable. The compounds have been developed in the past years
reversible features such as pain redness, heat and swelling (Mascolo, 1987; Alcaraz; Jiménez, 1988; Handa et al.,
are joined by a fifth and less transient feature, namely, 1992; Gorzalczany et al., 1996, Falcão et al., 2005). In
loss of function of involved organs. Therefore control this work we review specially the alkaloids isolated and
of inflammation is sought to protect the body function identified from the plants, previously demonstrated to
(Denko, 1992; Parnham, 1991). have an anti-inflammatory activity. These compounds
In the field of inflammation research, several have been selected, classified in appropriate subgroups
experimental models have been used to evaluate the and the data are reported based on their pharmacological
inflammation. The usual methods of determining activity in different experimental models.
whether compounds have anti-inflammatory activity
are to test them against animal and biochemical models MATERIAL AND METHODS
of inflammation. There is no experimental model of
inflammation that covers all aspects of inflammation The keywords used for this review were anti-
(Lewis, 1989). inflammatory activity plus alkaloids. The search was
The experimental models can be divided into done using Chemical Abstracts, Biological Abstracts and
two broad classes: (1) acute inflammatory models and (2) in the data bank of University of Illinois in Chicago –
chronic inflammatory models. Acute models are designed NAPRALERT (Acronym for NAtural PRoducts ALERT),
to test drugs that modulate blood flow (erythema), updated until December 2000. The references found in
changes in vascular permeability, leukocyte migration and the search were later consulted.
chemotaxis, phagocytosis - PMNLs and other phagocytic
cells, measurement of local pain, antipyretic activity, RESULTS AND DISCUSSION
local analgesic action and rat paw edema. Chronic models
are designed to find drugs that may modulate the disease Alkaloids are most common in flowering plants,
process and these include sponge and pellet implants and and usually in the Papaveraceae (poppies), Papilonaceae
granuloma pouches which deposit granulation tissue, (lupins), Ranunculaceae (aconites), and Solanaceae
adjuvant induced arthritis and rabbit monoarticular (tobacco and potatoes). They are also found in lower
arthritis which have an immune etiology (Lewis, 1989). plants, insects, marine organisms, microorganisms and
Experimental inflammation in whole animal is the animals (Lewis, 1989).
usual starting point for anti-inflammatory testing. These The pharmacological studies in alkaloids have
experiments are varied and widely used, specially the been largely concerned with the effect of alkaloids on
rat paw edema test. It can be adapted in numerous ways physiological processes other than inflammation.
using different inflammatory agents in attempt to mimic Only one alkaloid, colchicine is an established
pathological inflammation and arthritis (Willianson, clinical agent for arthritic disease and leukocytoclastic
1996). vasculitis (Sais et al., 1995). The alkaloid is present
It has been demonstrated numerous in corns and seeds of crocuslike plants. Colchicine is
physiological changes that find a parallel in human best known for its preventive action against gout, but
disorders such as different forms of arthritis and it also reduces pain and swelling in degenerative and
acute inflammation. These responses to inflammation immunological inflammatory disease (Malkinson, 1982).
include variation in temperature, leukocyte counting, Isoquinoline, indole and diterpene alkaloids
sedimentation rate. were the most studied about their activities on
Natural products have long been recognized as an inflammation. Aconitine and others alkaloids from
important source of therapeutically effective medicines. Aconitum genus were screened for anti-inflammatory
Of the 520 new drugs approved between 1983 and 1994, activity. They were effective on different assays including
39% were natural products or derived from natural carrageenin-induced paw o edema, adjuvant-induced
Rev. Bras. Farmacogn.
110 Braz J. Pharmacogn.
16(1):jan/mar. 2006
Anti-inflammatory activity of alkaloids A twenty-century review

arthritis and acetic acid induced vascular permeability helping with the computer aided NAPRALERT search of
tests (Benn; Jacyno, 1983; Luo et al., 1991; Zhang et al., antiinflammatory activity.
1982; Hikino et al., 1982; Saito et al., 1982). There are
about 500 species of Aconitum and the species has been REFERENCES
intensively investigated for the pharmacological activity
of their alkaloids. Since anti-rheumatic properties have Akhter MH, Sabir M, Bhide NK 1977. Anti-inflammatory effect
been associated with this plant, some attention has been of berberine in rats injected locally with cholera
toxin. Indian J Med Res 65: 133-135.
made to the anti-inflammatory activity of alkaloids in
Alcaraz MJ, Jiménez MJ 1988. Flavonoids as anti-inflammatory
Aconitum (Lewis, 1989). agents. Fitoterapia 59: 25-38.
Several isoquinoline alkaloids (berbamine, Alkiewicz J 1983. Clinical evaluation of an aerosol medicinal
berberine, cepharanthine and tetrandine) were examined plant preparation in vibratory therapy of maxillaris
for anti-inflammatory activity. They showed to be active in sinusitis of children. Herba Pol 29: 281-286.
different assays as reported by different authors (Wong et Anonymous 1974. Antipyretic anti-inflammatory and analgesic
al., 1992; Yasukawa et al., 1993; Ono, 1994; Hikino et al., medicine. Patent-Fr Demande-2,215,218, apud
1980). For instance, tetrandrine, a bisbenzylisoquinoline Chemical Abstracts 83: 65461.
alkaloid extracted from the root of the creeper Stephania Apoyan NA, Tumadzhyan AE, Chilingaryan DG, Melik-
Guseinov VV, Mnatsakanyan VA, Murav’eva DA
tetrandra S. Moore (Menispermaceae) has been shown
1984. Anti-inflammatory properties of oridine
to inhibit neutrophil and monocyte functions, including hydrochloride. Biol Zh Arm 37: 603-605, apud
adherence, locomotion and superoxide generation (Seow Chemical Abstracts 101: 183650.
et al., 1986; Seow et al., 1988) and the plant has been Arens H, Fischer H, Leyck S, Romer A, Ulbrich B 1985. Anti-
used for the treatment of rheumatic diseases, silicosis and inflammatory compounds from Plagiorhegma
other chronic inflammatory disease (Binggi et al., 1983). dubium cell culture. Planta Med 51: 52-56.
Several studies showed that the alkaloid suppress antigen Backhouse N, Delporte C, Givernau M, Cassels BK, Valenzuela
and mitogen-induced lymphocyte proliferation, natural- A, Speisky H 1994. Anti-inflammatory and
Killer cell cytotoxicity, histamine release by mast cells, antipyretic effects of boldine. Agents Actions 42:
114-117.
interleukin-1 (IL-1) secretion by human monocytes and
Bamgbose SOA, Noamesi BK 1981. Studies on cryptolepine.
the action of PAF on platelets (Seow et al., 1989). Teh et Planta Med 41: 392-396.
al. (1989 and 1990) showed that tetrandine and its natural Barik BR, Bhowmik T, Dey AK, Patra A, Chatterjee A, Joy S,
analogue, berbamine inhibit prostaglandin and leukotriene Susan T, Alam M, Kundu AB 1992. Premnazole,
generation by human monocytes and neutrophils in dose- an isoxazole alkaloid of Premna integrifolia and
dependent manner. Gmelina arborea with anti-inflammatory activity.
Berbarine is a major compound present in Fitoterapia 63: 295-299.
Phellodendri cortex and Coptidis rhizoma and the plant Basu A, Lahiri SC 1977. Some pharmacological actions of
has been used for the treatment of diarrhea and other solasonine. Indian J Exp Biol 15: 285-289.
Bekemeier H, Leuschner G, Schmollack W 1968. Antipyretic,
gastrointestinal disease in Japan and some Eastern
antiinflammatory, and analgetic effect of
countries. Ivanovsk; Philipov (1996) and Yasukawa et al. damascenine. 4th Meeting Conf Hung Ther Invest
(1991) showed berbarine had an inhibitory effect on the Pharmacol, Soc Pharmacol Hung 449-451.
ear TPA-induced inflammation indicating that this alkaloid Benn MH, Jacyno JM 1983. The toxicology and pharmacology
may have important activity in chronic inflammation. of diterpenoid alkaloids. Alkaloids: Chemical and
The alkaloids tend to be rather toxic, although Biological Perspectives. SW Pelletier (Ed), John
the toxicity appears to be well below the therapeutic Wiley & Sons, NY v 1, 153-210.
levels. The alkaloids appear to offer the considerable Berezhinskaya VV 1972. New neurotropic drugs of the quinoline
promise for further investigation as anti-inflammatory and isoquinoline alkaloid series. Postep Dziedzinie
Leku Rosl Pr Ref Dosw Wygloszone Symp 164-171,
compounds, and some appears to be remarkably active.
apud Chemical Abstracts 78: 119087.
Of the 171 evaluated alkaloids, 137 presented Bertelli A, Cogni G, Testi G 1956. The antipermeability effect
anti-inflammatory activity, and among those, the of reserpine. Boll Soc Ital Biol Sper 32: 832.
isoquinoline type was the most studied. The Carrageenin- Bhat SV, Shah V, Dohadwalla AN, Mandrekar SS, De Souza
induced pedal edema was the most used model for NJ 1986. Isolation of a pharmacologically active
evaluating the anti-inflammatory activity. In this review, substance having the structure of a chromone
174 references were cited. alkaloid from plant(s) belonging to the Meliaceae
family. Patent-Indian-157,282, apud Chemical
Abstracts 106: 38467.
Binggi L, Changgi Z, Yurui L 1983. Studies on the contents
ACKNOWLEDGEMENTS
of glycosaminoglycans from lungs of silicotics rats
and tetrandrine treated silicotic rats. Ecotoxic Envir
The authors wish to express their sincere thanks Safety 7: 323-329.
to College of Pharmacy, The University of Illinois at Birkner C, Stapel G, Leyck S, Fischer H, Christ B, Kesselring K
Chicago, Chicago, Illinois 60612-7231, U.S.A., for 1986. Extraction of hopamidine. Patent-Ger Offen-
Rev. Bras. Farmacogn.
Braz J. Pharmacogn.
111
16(1):jan/mar. 2006
José M. Barbosa-Filho, Márcia R. Piuvezam, Marcelo D. Moura, et al.

Table 1. Alkaloids isoquinoline summary showing anti-inflammatory activity

Isoquinoline Structure Effect Assay References


Alkaloids
Berbamine OMe MeO Active Air-pouch/carrageenin, IL- Wong et al., 1992
1, TNF or PAF-induced
MeN NMe inflammation;
OMe
H O H Aracdonic acid induced Yasukawa et al.,
O inflammation; 1993
TPA induced inflammation; Ono, 1994
OH Adherence, locomotion and Li et al., 1989
3-Hdeoxyglucose uptake
neutrophils were suppressed
Sheep red blood cell; Wong et al., 1991
Trinitrochlorobenzeine and Naidovich et al.,
Brucella abortus induced 1976
delayed type
hypersensitivity

Berbamunine OMe MeO Inactive Carrageenin-induced pedal Sadritdinov, 1980


edema
MeN NMe
OH HO
H H
O

OH

Berberine O Weak Adjuvant-induced arthritis; Ivanovska;


activity Philipov, 1996
N
O Inactive Carrageenin-induced Akhter et al., 1977
OMe inflammation;
Granuloma on chorio- Otsuka et al., 1981a
allantoic membrane of
OMe Active fertilized eggs; Hikino et al., 1977
Xilene-induced ear swelling Zhang et al., 1990
Carrageenin-induced pedal
edema; Akhter et al., 1977
Cholera toxin or formalin
induced inflammation
Croton pellet granuloma
pouch; Endo et al., 1979
Granulation tissue using
fertile eggs; Otsuka et al., 1981a
Cotton oil granuloma Hikino et al., 1980
pouch;
Granulation tissue on chick Otsuka et al., 1982
embryo chorio-allantoic
membrane;

Boldine HO Active Carrageenin-induced pedal Backhouse et al.,


edema 1994
NMe
MeO
H

MeO
OH
Boldine (+) HO Inactive Intracolonic acetic acid- Gotteland et al.,
induced colitis, edema, 1997
NMe neutrophil, infiltration and Grupta; Bhakuni,
MeO
H myeloperoxidase activity 1989
were all decreased; Lanhers et al., 1991

MeO
OH

Boldine, nor HO Inactive In vivo, route not given Grupta; Bhakuni,


Dose not stated 1989
NH
MeO
H

MeO
OH

Rev. Bras. Farmacogn.


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Anti-inflammatory activity of alkaloids A twenty-century review

Cepharanoline OMe O Active Inflammation inhibitor Ono, 1994

MeN NMe
O O
H H

OH

Cepharanthine OMe O Active Aracdonic acid induced Yasukawa et al.,


inflammation; 1993
MeN NMe TPA induced inflammation Ono et al., 1994a
O O
H H Chronic inflammation and
TNF-α production;
O
Carrageenin-induced pedal Ono et al., 1994b
OMe edema;
Crotton-oil-induced edema Yasukawa et al.,
Hstamine induced edema 1991
TPA-inducer ear edema;
Inactive Granuloma formation Fujiwara et al.,
induced with a sc implant of 1980
hcho-soaked filter paper

Chelerythrine O Active Carrageenin-induced pedal Ulrichova et al.,


edema 1984
O Carrageenin-induced pedal Lenfeld et al., 1981
NMe edema
MeO
OMe

Coclaurine MeO Inactive Granuloma pouch Kimura et al., 1985


NH
HO
H

HO

Coclaurine, methyl MeO Inactive Granuloma pouch Kimura et al., 1985


Concanavalin-A induced
NMe inflammation;
HO
H Antigen-antibody IG-E
induced inflammation

HO

Colchiceine MeO Active In vivo, rat Kiselev, 1977


NHAc
MeO
MeO O

OH

Colchicine MeO Active Mustard oil-induced edema; Morita, 1926


NHAc Pericarditis; Millaire; Ducloux,
MeO 1992
Fibromatosis palmar; Pitts-JR, 1995
MeO O Chronic cutaneouos Plotnick et al., 1989
leukocytoclastic vasculitis;
OMe Familiar mediterranean Kiselev, 1977
fever;
Pustulosis palmaris; Takigawa et al.,
1982

Corydaline, MeO Active Edema formation; Matsuda et al.,


dehydro Acetic-acid-induced 1997
N vascular permeability;
MeO
Serotonin or bradykinin-
OMe
Me induced edema;
Histamine-induced edema;
OMe LTC4-induced edema

Rev. Bras. Farmacogn.


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Corydine, iso HO Inactive In vivo Gupta; Bhakuni,


1989
NMe
MeO
H
HO

MeO

Corytuberine MeO Inactive In vivo Gupta; Bhakuni,


1989
NMe
HO
H
HO

MeO

Cycleanine OMe Active In vivo Berezhinskaya,


1972
MeN
OMe
H O H
O MeO
NMe

MeO

Daphnoline OMe MeO Active Rat paw edema model; Yamahara et al.,
1974a
HN NMe Dextran induced pedal Salama et al., 1987
O HO
H H edema; Rios et al., 1989
Carrageenin induced pedal
O
edema
OH

Dauricine OMe MeO Active In vivo Yamahara et al.,


1974b
MeN NMe
OMe MeO
H H

O
OH

Dicentrine O Inactive In vivo Gupta; Bhakuni,


1989
NMe
O
H

MeO
OMe

Dicentrine nor O Inactive In vivo Gupta; Bhakuni,


1989
NH
O
H

MeO
OMe

Emetine MeO Active Decrease of granulation Otsuka et al., 1981c


tissue on chick embryo
N chorioallantoic membrane
MeO
H

H
H
OMe
HN

OMe

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Fetidine OMe MeO Active Formalin-induced pedal Sadritdinov, 1972


edema
MeN NMe
OMe HO
H H
OMe O

OMe MeO

Fangchinoline OMe MeO Actve Cytokine production Onai et al., 1995


inhibition; Choi et al., 2000
MeN NMe Yeast-induced inflammation Hristova; Istatkova,
OH
O of the paw 1999
O

OMe

Glaucine MeO Active Granuloma pouch assay; Nikolov, Peneva,


1978
NMe Inactive Carrageenin-induced pedal Pinto et al., 1998
MeO
H edema

MeO
OMe

Haemanthidine OMe Active Carrageenan-induced pedal Citoglu et al., 1998


OH edema
O
H
N
O
OH
Higenamine HO Active Histamine induced paw Zhang, 1985
edema;
NH As measured by edema Shin et al., 1996
HO
H volume in hind paw

HO

Hydrastine O Inactive Decrease of granulation Kisolov, 1978


tissue on chick embryo
NMe
O chorioallantoic membrane
H H

O
OMe
O OMe

Jatrorrhizine Active In vivo Arens et al., 1985


HO
MeO N

OMe
OMe

Liriodenine O Inactive Granuloma pouch Kimura et al., 1985


N
O

Lycorine OH Active Formalin arthritis; Chen et al., 1965


HO Egg white induced pedal
H edema;
O Egg white induced pedal
H edema in adrenalectomized
N
O rats

Rev. Bras. Farmacogn.


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115
16(1):jan/mar. 2006
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Magnoflorine MeO Inactive In vivo Gupta; Bhakuni,


1989
NMe2
HO
H
HO

MeO

Morphine HO Active Given prior to topical Morita, 1926


mustard oil

O
NMe
H
HO

Narciclasine OH Active Adjuvant-induced arthritis Mikami et al., 1999


OH
H
O
OH
NH
O
OH O

Norarmepavine MeO Inactive Edema in the Randall- Kupchan et al.,


Selitto antiinflammatory test 1963
NH
MeO
H

HO

Obaberine OMe MeO Actve Carrageenin-induced pedal Sadritdinov, 1980


edema
MeN NMe
O MeO
H H

OMe

Oliverine O Active Formalin-induced pedal Sadritdinov;


edema Sultanov, 1971
NMe
O
H
OMe

OMe

Oridine MeO Active Carrageenin-induced pedal Apoyan et al., 1984


edema
NH
HO
H

HO
H

Papaveraldine MeO Actve Carrageenin-induced pedal Buzas et al., 1974


edema
N
MeO
MeO
O

MeO

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Protopine O Active Dext.-induced pedal edema Molokhova et al., 1973


Me
N
O
O
O

Reticuline MeO Inactive Granuloma Pouch Kimura et al., 1985

NMe
HO
H
HO

MeO

Sanguinarine O Active Carrageenin-induced pedal Ulrichova et al., 1984


edema Hu et al., 1979
O Cerna et al., 1984
NMe Lenfeld et al., 1981
O
O

Sinoacutine MeO Active Phlogistic response Dekker et al., 1988

HO

NMe

MeO
O

Sinomenine MeO Active Mustard oil-induced edema Morita, 1926

HO

NMe
H
O
OMe

Taspine MeO NMe2 Active Carrageenin-induced pedal Persinos, 1972


edema;
O Adjuvant-induced arthritis Perdue et al., 1979
O
Cotton pellet granuloma
O
O Adjuvant poly arthritis

OMe

Tetrandrine OMe MeO Active Carrageenin-induced pedal Yamahara, 1974a


edema; Choi et al., 2000
MeN NMe Aseptic or formalin induced Sadritdinov, 1974
OMe
H O H inflammation;
O Carrageenin-induced Wong et al., 1992
inflammation;
OMe Interleukin induced Naidovich et al., 1976
inflammation

Tetrandrine, demethyl OMe MeO Active Aseptic or formalin-induced Sadritdinov, 1974


inflammation
MeN NH
OMe
H O H
O

OMe

Tetrandrine, iso OMe MeO Active Arachidonic acid induced Yasukawa et al., 1993
inflammation;
MeN NMe Phorbol ester induced
OMe
H O H inflammation; Onai et al., 1995
O Cytokine production inhibition.

OMe

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Thalicsimine OMe Active Aseptic or formalin-induced Sadritdinov; Sultanov,


OMe MeO inflammation 1971

MeN NMe
OMe
H O H
O

OMe

Thalieberine, O-methyl OMe MeO Active Mouse pedal edema assay Sadritdinov; Sultanov,
1971
MeN NMe
OMe
H O
O

OH

Thalmine OMe Active Mouse pedal edema assay Sadritdinov; Sultanov


HO
O
1971
MeN NMe
MeO
H H
O

OMe

Trilobine MeO Active In vivo Yamahara et al., 1974b


MeN O
NH
O
H H

O
OMe

Trilobine, iso MeO Active In vivo Yamahara et al., 1974b


MeN O
NMe
O
H H

O
OMe

Tubocurarine OMe Inactive Decrease of granulation tissue Otsuka et al., 1981a


on chick embryo chorioallantoic
Me2N
OH membrane
H O H
O NHMe

OH
MeO

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Table 2. Alkaloids indole summary showing anti-inflammatory activity

Indole Alkaloids Structure Effect Assay References


Ajmaline OH Active Carrageenin-induced pedal Saeed et al., 1993
edema
H
N
N H OH
Me

Alstonine, H Week Carrageenan-induced pedal Kocislski et al., 1972


tetrahydro activity edema
H
N
N
H
Me
H
MeO O

Annomontine Active In vivo Leboeuf et al., 1982


N
N
H
N

N NH2

Annomontine, MeO Active In vivo Lebouef et al., 1982


methoxy
N
N
H
N

N NH2

Brucine H Inactive Carrageenin-induced pedal Tits et al., 1991


N
MeO edema
H
MeO N
H H
O
H O

Cryptolepine Me Active Carrageenin-induced pedal Noamesi; Bamgbose,


N edema 1983
Bamgbose; Noamesi,
1981
N

Evodiamine Active Carrageenan-induced pedal Matsuda et al., 1998


H edema;
N O Serotonin induced edema;
N
H Bradykinin-induced edema;
N
Me Arachidonic acid-induced
ear swelling

Holstiine Me Inactive Carrageenin-induced pedal Bamgbose; Noamesi,


N edema 1981
O
Tits et al., 1991
H
N
H H
O O
H
OH

Melatonin NH Active Carrageenin-induced pedal Mimura et al., 1982


edema
O
N
H

Rev. Bras. Farmacogn.


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Ochropamine MeOOC
H
Active In human, oral Anonymous, 1974

Me
N
N
O
Me

Paniculidine B Active In vivo, IP, rat Somei, 1987


OH

N
OMe

Reserpine Active Egg albumin edema Bertelli et al., 1956


N
MeO N
H H
H
O
H
OMe
MeOOC O
OMe
OMe
OMe

Retuline, iso: O-acetyl N Inactive Carrageenin-induced pedal Tits et al., 1991


edema;

Active Zymosan induced paw edema


N
H
Ac OAc

Rutaecarpine Active Carragennan-induced pedal Moon et al., 1999


edema;
N O
N Active Serotonin-induced edema; Matsuda et al., 1998
Inactive Histamine-induced edema
H N

Staurosporine H Inactive TPA-induced skin inflammation Yamamoto et al., 1989


N O

N N
O

MeO
NHMe

Strychnine N Inactive Decrease of granulation tissue Otsuka et al., 1981a


H on chick embryo chorioallantoic
membrane
H H H
N

O O
H

Tabernaemontanine MeOOC H Active In human, oral Anonymous, 1974

O
NMe
N
H
H

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Vincaleukoblastine Active Claimed useful in the treatment Anonymous, 1974


N
of rheumatoid arthritis
OH
N
H
H N
MeOOC

H
MeO N OAc
H
Me HO COOMe

Vobasine MeOOC H Active In human, oral Schinitsky, 1980

O
NMe
N
H

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Table 3. Alkaloids diterpene summary showing anti-inflammatory activity

Diterpene Alkaloids Structure Effect Assay References


Aconine, 14 anisoyl HO OMe Active Paw-swelling method Murayama et al., 1991

MeO H OBzOMe
H

Et N
OH OH
HO H
OMe OMe

Aconine benzoyl HO OMe Active Carrageenin-induced pedal Benn; Jacyno, 1983


edema
MeO H OBz
H

Et N
OH OH
HO H
OMe OMe

Aconitine HO OMe Inactive Topical mustard oil; Morita, 1926

MeO H OBz Active UV light-induced erythema; Benn; Jacyno, 1983


H Kitagawa et al., 1984
Carrageenin-induced pedal Luo et al., 1991
Et N edema;
OH
OAc
HO H Adjuvant-induced arthritis Benn; Jacyno, 1983
OMe OMe Increase of vascular;
Permeability induced by
acetic acid.

Aconitine, 3 acetyl HO OMe Active Increased of vascular Tang et al., 1984


permeability induced by
MeO H OBz acetic acid;
H Cotton pellet granuloma
Et N
OH
OAc
AcO H
OMe OMe

Delphinine Iso OMe Inactive In vivo Zhang et al., 1982


MeO H OBz
H

Me N
OH
OAc
AcO H
OMe OMe

Hypaconitine HO OMe Active Adjuvant-induced arthritis Luo et al., 1991


Benn; Jacyno, 1983
MeO H OBz Zhang et al., 1982
H

Me N
OH
OAc
AcO H
OMe OMe

Ignavine Active Carrageenin-induced pedal Saito et al., 1983


edema Saito et al., 1982
PhCOO
OH
N OH
HO

Mesaconitine HO OMe Active Adjuvant induced pedal Luo et al., 1991


edema;
MeO H OBz Inactive Carrageenin-induced pedal Hikino, 1982
H edema;
Histamine-induced pedal
Me N edema;
OAc OH
HO H 5-HT-induced pedal edema;
OMe OMe PGE-1-induced pedal edema;
Bradykinin-induced pedal
edema.

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Neoline OMe Active In vivo Zhang et al., 1982

HO H OH
H

Et N
OH
H
OMe OMe

Neoline, 15-alpha- OMe Active In vivo Zhang et al., 1982


hydroxy
HO H OH
H

Et N OH
OH
H
OMe OMe

Pyroaconitine HO OMe Active Carrageenin-induced pedal Murayama et al., 1991


edema
MeO OOCPh

Et N
H O
HO H
OMe OMe

Pyroaconitine, 16 epi HO OMe Active Carrageenin-induced pedal Murayama et al., 1991


edema
MeO OOCPh

Et N
H O
HO H
OMe OMe

Pyrohypaconitine HO OMe Active Carrageenin-induced pedal Murayama et al., 1991


edema
MeO OOCPh

Me N
H O

OMe OMe

Pyrojesaconitine HO OMe Active Carrageenin-induced pedal Murayama et al., 1991


edema
H OBzOMe
H

N
H O
HO H
OMe OMe

Pyrojesaconitine, 16 HO OMe Active Carrageenin-induced pedal Murayama et al., 1991


epi edema
MeO H OBzOMe
H

N
H O
HO H
OMe OMe

Pyromesaconitine HO OMe Active Carrageenin-induced pedal Murayama et al., 1991


edema
MeO H OOCPh
H

Me N
H O
HO H
OMe OMe

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Pyromesaconitine, HO OMe Active Carrageenin-induced pedal Murayama et al., 1991


16 epi edema
MeO H OOCPh
H

Me N
H O
HO H
OMe OMe

Spiramine K Active In vivo Fuji et al., 1991

N
H OH

Thalicsiline OH Active Carrageenin-induced pedal Wu et al., 1988


edema

N O

H
O OAc
H

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Table 4. Alkaloids steroid summary showing anti-inflammatory activity

Steroid Alkaloids Structure Effect Assay References


Cevadine H Inactive Topical mustard-oil Morita, 1926
Endotoxin induced posterior
H uveitis
N
HO
OH
H H OH
O O OH
OH
O H
OH

Cyclobuxine D NHMe Active Formalin-induced arthritis Saidkasymov, 1978

OH Ovalbumin-induced arthritis

MeHN

Edpetiline H Active Kaolin-induced Saidkasymov et al.,


inflammation; 1971
H
N
Egg albumin induced
H H OH inflammation
H H

OH
H H
Glu O H
O

Funtumidine HO Active Edema in the rat's paw Blanpin;


H Quevauviller, 1960

H H
H 2N
H

Funtumine O Active Edema in the rat's paw Blanpin;


Quevauviller, 1960

H H
H2N
H

Gitingensine O O Inactive Histamine-induced Estrada et al., 1966


ventilation overflow
H
H

H H
H 2N

Holamine O Active Not specified Oletta, 1964

H H
H 2N

Holaphyllamine O Active Not specified Oletta, 1964

H H
H2N

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Holaphylline O Active Not specified Oletta, 1964

H H
MeHN

Petiline Active Egg albumin induced Saidkasimov et al.,


inflammation; 1971
H N Kaolin-induced
inflammation

HO
H
O

H
Solasonine Active Cotton pellet granuloma Basu; Lahiri, 1977
NH Carrageenin-induced pedal
H
edema
O
H H

OH
H H
OH O O
OH
O O
OH
OH OH O O
OH Me

OH OH

H
Tomatine Active Carrageenan induced paw Filderman; Kovacs,
NH edema; 1969
H
O Granulation tissue
H H
formation induced by the
OH OH H H
O O
O O O O s.c. implantation of
OH H

OH
OH
OH
OH
carrageenan impregnated
OH OH
O
O
cotton pellets;
OH
OH I.p. injection of acidified
OH
saline and i.v. pontamine
sky blue

Veralosine Active In vivo, rat Saidkasymov, 1978

OAc

OH
OH O O
OH

OH

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Table 5. Alkaloids amide summary showing anti-inflammatory activity

Amide Alkaloids Structure Effect Assay References


Capsaicin O Weak Carrageenin-induced pedal Reddy; Lokesh,
MeO
NH
activity edema; 1994
Active Non-allergic rhinits; De; Ghosh et al.,
HO Mycobacterium tuberculosis- 1988
induced polyarthritis; Clarke, 1993
Rheumatoid arthritis or Cruwys et al., 1995
osteoarthritis;
Carrageenin-induced McCarthy et al.,
inflammation; 1992
Adjuvant-induced arthritis.
Raychaudhuri et
al., 1991
Hara et al., 1984
Joe; Lokesh, 1997

Fagaramide O Active Carrageenin-induced pedal Oriowo, 1982


O
edema
NH

Piperine O Active Carrageenin-induced pedal Reddy; Lokesh,


O
edema; 1994
N Histamine-induced edema; Lee et al., 1984
O
Formalin-induced pedal edema; Munjudar et al.,
Cotton pellet granuloma 1990
Granuloma pouch

Riparin I Inactive Carrageenan-induced pedal Castelo-Branco et


edema al., 2000
NH

O
MeO

Riparin II Inactive Carrageenan-induced pedal Castelo-Branco et


edema al., 2000
NH

O HO
MeO

Riparin III HO Inactive Carrageenan-induced pedal Castelo-Branco et


edema al., 2000
NH

O HO
MeO

Volutamide B Me H NHMe Active Phorbol ester induced ear Montanari et al.,


MeO N N inflammation 1996
O
Br Br

Volutamide C Me H NMe2 Active Phorbol ester induced ear Montanari et al.,


MeO N N inflammation 1996
O
Br Br
Volutamide D Me NMe2 Active Phorbol ester induced ear Montanari et al.,
MeO N inflammation 1996

O
Br Br

Br
OMe

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Table 6. Alkaloids quinolizidine summary showing anti-inflammatory activity

Quinolizidine Structure Effect Assay References


Alkaloids
Cryogenine O Active Carrageenan-induced pedal Kocialski et al., 1972
edema; Kaplan et al., 1967
H O Chronic anti-inflammatory
HO evaluation;
Adjuvant-induced arthrits Omaye et al., 1972
N
H H
MeO
OMe

Lupanine, 17 oxo O Active Carrageenin-induced pedal Murakoshi et al., 1992


H edema
N

N
H
O

Lythrine O Active Carragenin-induced pedal Byrne; Malone, 1981


edema
H O
HO

N
H H
MeO
OMe

Matrine O Active Decrease ear inflammation Tan; Zhang, 1985


H
N
H

H H
N

Matrine, oxy O Active In vivo, rat Ma et al., 1991


H
N
H

H H
N
O

Nesodine O Active Active Handa et al., 1992

H O
HO
MeO
N
H H
MeO

Sparteine O Active Croton-oil induced edema Chang, Malone, 1971


H
N

N
H
O

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Table 7. Alkaloids quinoline summary showing anti-inflammatory activity

Quinoline Alkaloids Structure Effect Assay References


Acronycidine OMe OMe Inactive Erythema block Svoboda; Kattau,
1967

MeO N O
OMe

Cinchonine H Active Mustard oil-induced edema Morita, 1926

HO
H N
H

Quinidine H Active Mustard oil-induced edema Morita, 1926

HO
H N
H
MeO

Quinine H Active Mustard oil-induced edema; Morita, 1926


Decrease of granulation tissue on Otsuka et al., 1981b
HO chick embryo chorioallantoic
H N membrane;
H Carrageenan-induced pedal Santos; Rao, 1998
MeO
edema

Skimmianine OMe Active TPA-induced inflammation Garcia-Argaez et al.,


2000

MeO N O
OMe

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Table 8. Alkaloids purine summary showing anti-inflammatory activity

Purine Alkaloids Structure Effect Assay References


Adenine NH2 Inactive Fertille egg method Otsuka et al., 1974
N
N

N NH

Adenosine NH2 Active Inhibited TNFα mediated Parmely et al., 1993


N
inflammation responses
N

N N
HO
O

OH OH

Caffeine O Active Phorbol acetate induced edema; Yasukawa et al., 1991


Formalin-induced pedal edema.
NMe
MeN Inactive Sawynok et al., 1995
O N N
Me

Theophylline O Active Adjuvant-induced arthritis; Revesz et al., 1992


Dextran-induced pedal edema;
NH
MeN Carrageenin-induced pedal Sullivan et al., 1994
edema
O N N
Me

Table 9. Alkaloids aliphatic summary showing anti-inflammatory activity

Aliphatic Structure Effect Assay References


Alkaloids
Desferrioxamine H2N(CH2)5N(OH)CO(CH2)2CONH(CH2)5N(OH) Active Antigen-induced inflammation Yoshino et al.,
1984
Ac(OH)N(CH2)5NHCO(CH2)5CO

Putrescine H2NCH2CH2CH2CH2NH2 Inactive Effect chemotaxis; Haigh et al., 184


Active Serotonin induced paw edema Suzuki et al., 1983

Spermidine H2N(CH2)3NH(CH2)4NH2 Active Serotonin induced pedal edema Suzuki et al., 1983

Spermine H2N(CH2)3NH(CH2)4NH(CH2)3NH2 Active Serotonin induced pedal edema Suzuki et al., 1983

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Table 10. Alkaloids monoterpene summary showing anti-inflammatory activity

Monoterpene Structure Effect Assay References


Alkaloids
Gentianadine O Active In vivo, oral, rat Sadritdinov, 1972

Gentianamine HO Active Formalin-induced pedal edema Sadritdinov, 1971


O

Gentianidine O O Week Formalin-induced pedal edema Sadritdinov, 1971


activity

Gentianine O Active Mouse paw edema test; Tulyaganov, 1971


Formalin-induced-pedal edema; Sung et al., 1958
O Egg white-induced pedal edema

Table 11. Alkaloids pirrole summary showing anti-inflammatory activity

Pirrole Alkaloids Structure Effect Assay References


Ganoderma A Active In vivo Yang; Yu, 1990
OHC N
OH

Ganoderma B Active In vivo Yang; Yu, 1990

OHC N
OH

Hopamidine H Active Cobra venom. Induced edema Birkner et al., 1986


N

NH

NH2

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Table 12. Alkaloids phenetylamine summary showing anti-inflammatory activity

Phenetylamine Structure Effect Assay References


Alkaloids
Ephedrine CH3 Active Dinitrofluorbenzene-induced Hwang et al., 1990
HO-CH-C-NHCH3 swelling;
H Carrageenin, PGE-1, histamine, Kasahara et al., 1985
serotonin and bradikinin-induced
pedal edema;
Carrageenin-induced pedal Alkiewicz, 1983
Active edema;
Increased vascular permeability Hikino et al., 1980
Inactive induced by acetic acid, resistence
of heat-induced hemolysis of rat
RBC, decrease of granulation
tissue on chick embryo chorio-
allantoic membrane

Ephedrine, N-methyl CH3 Inactive Carrageenin-induced pedal Hikino et al., 1980


HO-CH-CH-N(CH3)2 edema;
Resistence of heat-induced
hemolysis of rat RBC;
Weak Effect on increased vascular
activity permeability induced by acetic
acid

Ephedrine, pseudo H Active Dinitrofluorbenzene-induced Hwang et al., 1990


HO-CH-C-NHCH3 swelling;
CH3 Carrageenin-induced pedal Hikino et al., 1980
edema;
Effect on increased vascular
permeability induced by acetic
acid;
Active Carrageenin-induced pedal Hikino et al., 1980
edema;
Effect on increased vascular
Permeability induced by acetic
acid;
Inactive Resistence of heat-induced
hemolysis of rat RBC;
Weak Decrease of degranulation tissue
activity on chick embryo chorioallantoic
membrane;
Active Croton oil-induced edema Wang et al., 1996

Table 13. Alkaloids piperidine summary showing anti-inflammatory activity

Piperidine Alkaloids Structure Effect Assay references


Arecoline Me Inactive Granulation tissue on chick Otsuka et al., 1981b
N embryo chorioallantoic membrane

OMe

Rohitukine OH O Active Carrageenin-induced pedal edema Naik et al., 1988


Bhat et al., 1986
Lakdawala et al.,
1988
HO O Me
H
OH

N
Me

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Table 14. Alkaloids piridine summary showing anti-inflammatory activity

Piridine Alkaloids Structure Effect Assay references


Anabasamine Active Dextran, serotonin, histamine Mukhamedzhanova
induced pedal edema 1984
N
Me
N

Nicotine Inactive Decrease of granulation tissue Otsuka et al., 1981a


N
on chick embryo chorioallantoic
H membrane
Me
N

Table 15. Alkaloids indolizidine summary showing anti-inflammatory activity


Indolizidine Alkaloids Structure Effect Assay References
Castanospermine OH OH Active Passively induced experimental Willenborg et al., 1990
H allergic encephalomyelitis
HO

N
HO

Tylophorine OMe Active Granuloma pouch assay; Gopalakrishnan et al.,


MeO Cotton pellet granuloma 1979
H

MeO
OMe

Table 16. Alkaloids tropane summary showing anti-inflammatory activity

Tropane Alkaloid Structure Effect Assay References


Cocaine Me
O Active Mustard-oil-induced edema Morita, 1926
N
OMe

H O

Scopolamine Me Inactive Decrease of granuloma tissue Otsuka et al., 1981a


N on chick embryo
chorioallantoic membrane
O
H

OCOCHPhCH2OH

Table 17. Alkaloids imidazolidine summary showing anti-inflammatory activity

Imidazolidine Alkaloids Structure Effect Assay References


Histamine H Inactive Decrease of granulation tissue on Otsuka et al., 1981a
N chick embryo chorioallantoic
membrane
N NH2

Pilocarpine H H Inactive Decrease of granulation tissue on Otsuka et al., 1981a


C2H5 Me
N chick embryo chorioallantoic
membrane
O O N

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Table 18. Alkaloids miscelane summary showing anti-inflammatory activity

Alkaloid-Miscelane Structure Effect Assay references


Allantoin O H Active Conjuctivitis due to irritation Fukahori et al.,
N 1990
H2NCONH N O
H

Anacrotine HO Active Carrageenin, hyaluronidase, Ghosh; Singh, 1974


O bradikinin or PG-induced pedal
edema
O
O O H

HO
N

Anthranilic acid COOH Active In vivo, rat male Yamasaki; Saeki,


1967
NH2

Apiodionen Active In vitro Takahashi et al.,


1992
O
O

N O
H

Arborine O Inactive Yeast-induced pedal edema Svoboda; Kattau,


1967
N

N
Me

Choline Inactive Fertile egg method Otsuka et al., 1974


(CH3)3NCH2CH2OH

Coixol NH Histamine release from rat Mast Otsuka et al., 1988


O cells.
MeO O

Cystine NH2 NH2 Inactive Carrageenan-induced pedal Madan; Al-Motrefi,


HOOC-CH-CH2-S-S-CH2-CH-COOH
edema 1986

Bukittinggine H Active Carrageenin-induced pleurisy; Panthong et al.,


N Carrageenin induced pedal 1988
HH edema;
Coton pellet granuloma;
H Adjuvant induced arthritis
O

Damascenine COOMe Active Formaldehyde-induced edema Bekemeier et al.,


of the rat 1968
NHMe
OMe

Gentianaine O Active Formalin-induced pedal edema Sadritdinov, 1971

NH2

O O

Premnazole N Active Cotton pellet granuloma Barik et al., 1992


O COOMe

Me

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Zoanthenamine, 28-deoxy O Active Phorbol ester induced Rao et al., 1989


H O
OH inflammation Sullivan et al., 1991
H O
O
H

3,506,643. Dekker TG, Fourie TG, Matthee E, Snyckers FO 1988. A


Blanpin O, Quevauviller A, 1960. Comparative pharmacology morphinan alkaloid from Antizoma angustifolia. J
of two alkaloids of steroid structure isolated from Nat Prod 51: 584.
Funtumia latifolia, funtumine and funtumidine. Denko CW 1992. A role of neuropeptides in inflammation. In:
Annales Pharmaceutiques Francaises 18: 177-192. Whicher, J. T. and Evans, S. W. Biochemistry of
Buzas A, Egnell C, Mathieu R, Bourillet F, Potherat JJ, Simon Inflammation. Kluwer Pub. London. 177-181p.
JC 1974. Synthesis and pharmacological properties Endo K, Taguchi T, Taguchi F, Hikino H, Yamahara J, Fujimura
of new papaveraldine oxime derivatives. Eur J Med H 1979. Antinflammatory principles of Atractylodes
Chem Chim 9: 571. C.A. 1975, 82: 171252f. rhizomes. Chem Pharm Bull 27: 2954-2958.
Byrne JA, Malone MH 1981. Protective effects of cryogenine, Estrada, Horacio R, Aguilar-Santos G 1966. Pharmacologic
lythrine and certain derivatives in croton oil induced and chemical studies on gitingensine, a new
inflammation. Proc West Pharmacol Soc 24: 183- azasteroidal alkaloid. Journal of the Philippine
187. Medical Association 42: 703-724.
Castelo-Branco UV, Castelo-Branco UJV, Thomas G, Evans SW, Whicher JT 1992. An overview of the inflammatory
Araújo CC, Barbosa-Filho JM 2000. Preliminary response. In: Whicher, J. T. and Evans, S. W.
pharmacological studies on three benzoyl amides, Biochemistry of inflammation. Kluwer Pub. London.
constituents of Aniba riparia (Lauraceae). Acta 1-15p.
Farm Bonaerense 19: 197-202. Falcão, HS, Lima IO, Santos VL, Dantas HF, Diniz MFFM,
Cerna H, Fiala B, Lenfeld J, Marsalek E, Preininger V, Simanek Barbosa-Filho JM, Batista LM 2005. Review of the
V 1984. Isoquinoline alkaloids in local periodontal plants with anti-infl ammatory activity studied in
disease therapy (preliminary notice). Acta Univ Brazil. Rev Bras Farmacogn 15: 381-391.
Palacki Olomuc Fac Med 107: 159-162. Filderman RB, Kovacs BA 1969. Antiinflammatory activity
Chang YC, Malone MH 1971. Anti-inflammatory and liver of the steroid alkaloid glycoside, tomatine. Brit J
sulfhydryl content-altering effects of certain Pharmacol 37: 748-755.
nonsteroids in the rat. J Pharm Sci 60: 416-419. Fuji K, Noide M, Kaku S, Shu T, Chin S 1991. Anti-inflammatory
Chang L, Yue Y, Zhou HW 1992. Effects of ligustrazine on diterpenes from Chrysanthemums. Patent-Japan
microvessel capillary hemodynamics in peritonitis Kokai Tokkyo Koho-03 86,824, apud Chemical
rabbit. Zhongguo Yike Daxue Xuebao 212: 117- Abstracts 115: 287166k.
119. Fujiwara R, Ono M, Orita K 1980. The effect of cepharanthine
Chen MC, Chin SC, Wang YC 1965. Effect of lycorine on the on granuloma formation in the rats. Igaku No
pituitary-adrenal system. Yao Hsueh Hsueh Pao 12: Ayumi 11: 1056-1057, apud Chemical Abstracts 94:
767-771. 58248u.
Choi HS, Kim HS, Min KR, Kim YS, Lim HK, Chang YK, Chung Fukahori K, Takahashi H, Uchino Y, Eino A 1990. Stable eye
MW 2000. Inflamamtory effects of fangchinoline drops containing vitamin E, FAD sodium salt,
and tetrandrine. J Ethnopharmacol 69: 173. allantoin, and glycyrrhizin. Patent-Japan Kokai
Citoglu G, Tanker M, Gumusel B 1998. Antiinflammatory Tokkyo Koho-02 311,415, apud Chemical Abstracts
effects of lycorine and haemanthidine Phytother 114: 254038
Res 12: 205-206. Garcia-Argaez AN, Ramirez-Apan TO, Delgado HP, Velazquez
Clarke IMC 1993. Peppering pain. Lancet 342 (8880): 1130. G, Martinez-Vasquez M 2000. Anti-inflammatory
Cragg GM, Newman DJ, Snader KM 1997. Natural products activity of coumarins from Decatropis bicolor on
in drug discovery and development. J Nat Prod 60: TPA ear mice model. Planta Med 66: 279-281.
52-60. Ghosh MN, Singh H 1974. Inhibitory effect of a pyrrolizidine
Cruwys SC, Garrett NE, Kidd BL 1995. Sensory denervation alkaloid, crotalaburnine, on rat paw edema and
with capsaicin attenuates inflammation and cotton-pellet granuloma. Brit J Pharmacol 51: 503.
nociception in arthritic rats. Neurosci Lett 193: 205- Gopalakrishnan C, Shankaranarayan D, Kameswaran L,
207. Natarajan S 1979. Pharmacological investigation of
De AK, Ghosh JJ 1988. Inflammatory effects of acute and tylophorine, the major alkaloid of Tylophora indica.
chronic capsaicin treatment on rat paw. Phytother Indian J Med Res 69: 513.
Res 2: 175. C.A. 1989, 110: 109677. Gorzalczany S, Acevedo C, Muschietti L, Martino V, Ferraro
Rev. Bras. Farmacogn.
Braz J. Pharmacogn.
135
16(1):jan/mar. 2006
José M. Barbosa-Filho, Márcia R. Piuvezam, Marcelo D. Moura, et al.

G 1996. Search for antiinflammatory activity in Kadota S, Matsuda S 1985. Anti-inflammatory


Argentine medicinal plants. Phytomedicine 3: 181- effect of neolignans newly isolated from the crude
184. drug “shin-i” (flos magnoliae). Planta Med 51: 291-
Gotteland M, Jimenez I, Brunser O, Guzman L, Romero S, 293.
Cassels BK, Speisky H 1997. Protective effect of Kiselev VV 1977. Relationship of structure and activity in the
boldine in experimental colitis. Planta Med 63: colchicine series. Chem Nat Comp 13: 1-10, apud
311-315. Chemical Abstracts 87: 47840k.
Gupta S, Bhakuni DS 1989. Alkaloids of Litsea deccanensis. Kitagawa I, Chen ZL, Yoshihara M, Kobayahsi K, Yoshikawa
Planta Med 55: 197. M, Ono N, Yoshimura Y 1984. Chemical studies
Haigh CG, Kafy AML, Lewis DA 1984. Observations of the on crude processing. III. Aconiti tuber (2). On the
anti-inflammatory action of putrescine. Brit J constitutents of “pao-fuzi”, the processed tuber of
Pharmacol 82: 283. Aconitum carmichaeli Debx and biological activities
Handa SS, Chawla AS, Sharma AK 1992. Plants with of lipo-alkaloids. Yakugaku Zasshi 104: 858-866.
antiinflammatory activity. Fitoterapia 63: 3-31. Kocialski AB, Malone MH, Marozzi FJ 1972. Effects of certain
Hara A, Sakurada T, Sakurada S, Matsumura H, Andoh R, nonsteroid antiinflammatory drugs, tolbutamide,
Kisara K 1984. Effects of capsaicin on adjuvant- and tetrahydroalstonine on blood-glucose and
induced chronic pain in rats. Ann Rep Tohoku Coll carrageenin-induced pedal edema in rats. J Pharm
Pharm 31: 153-159, apud Chemical Abstracts 103: Sci 61: 1202-1205.
153993n. Kupchan SM, Dasgupta B, Fujita E, King ML 1963. Alkaloids
Harborne JB 1991. Phytochemical methods. 2 ed. Chapman e of American lotus, Nelumbo lutea. Tetrahedron 19:
Hill. 288p. 227-232.
Henson PM, Murphy RC 1989. Mediators of the inflamatory Lakdawala AD, Shirole MV, Mandrekar SS, Dohadwalla
process. Elsevier, Amsterdam, 404p. AN 1988. Immunopharmacological potential of
Hikino H, Taguchi T, Fujimura H, Hiramatsu Y 1977. rohitukine: a novel compound isolated from the plant
Antiinflammatory principles of Caesalpinia sappan Dysoxylum binectariferum. Asia Pac J Pharmacol
wood and of Haematoxylon compechianum wood. 32: 91-98, Chemical Abstracts 109: 183182a.
Planta Med 31: 214-220. Lanhers MC, Joyeux M, Soulimani R, Fleurentin J, Sayag M,
Hikino H, Konno C, Takata H, Tamada M 1980. Studies on the Mortier F, Younos C, Pelt JM 1991. Hepatoprotective
constituents of Ephedra. VI. The validity of oriental and anti-inflammatory effects of a traditional
medicines. XV. Antiinflammatory principle of medicinal plant of chile, Peumus boldus. Planta
Ephedra herbs. Chem Pharm Bull 28: 2900-2904. Med 57: 110.
Hikino H, Takata H, Fujiwara M, Konno C, Ohuchi K 1982. Leboeuf M, Cave A, Forgacs P, Tiberghien R, Provost J, Touche
Mechanism of inhibitory action of mesaconitine in A, Jacquemin H 1982. Alkaloids of the Annonaceae.
acute inflammations. Eur J Pharmacol 82: 65-71. 40. Chemical and pharmacological study of the
Hristova M, Istatkova R 1999. Complement-mediated alkaloids of Annona montana Macf. Plant Med
antiinflammatory effect of bisbenzylisoquinoline Phytother 16: 169-184, apud Chemical Abstracts
alkaloid fangchinoline. Phytomedicine 6: 357-362. 97: 52498r.
Hu ZB, Xu Y, Feng SC, Fan GJ 1979. Studies on the active Lee EB, Shin KH, Woo WS 1984. Pharmacological study on
principles of the fruits of Macleaya cordata piperine. Arch Pharm Res 72: 127-132.
(Willd.) R. Br. Yao Hsueh Hsueh Pao 14: 535-540, Lenfeld J, Kroutil M, Marsalek E, Slavik J, Preininger V,
apud Chemical Abstracts 92: 185791z. Simanek V 1981. Antiinflammatory activity of
Hwang EJ, Kan EM, Yang KS, Park SB, Kim TH 1990. Effects quaternary benzophenanthridine alkaloids from
of ephedrae herba extract on cellular and humoral Chelidonium majus. Planta Med 43: 161-165.
immune responses. Korean J Pharmacog 213: 256. Lewis DA 1989. Anti-flamatory drugs from plant and marine
Ivanovska N, Philipov S 1996. Study on the anti-inflammatory sources. Birkhause Verlag, Basel.
action of Berberis vulgaris root extract, alkaloid Li SY, Ling LH, Teh BS, Seow WK, Thong YH 1989. Anti-
fractions and pure alkaloids. Int J Immunopharmacol inflammatory and immunosuppressive properties of
18: 553-561. the bis-benzylisoquinolines: In vitro comparisons of
Jamieson D, Buckle P 1977. A comparison of anti-inflammatory tetrandrine and berbamine. Int J Immunopharmacol
and other compounds on the spontaneously 11: 395-401.
contracting pregnant rat uterus. J Pharm Pharmacol Lim JK, Lee EB, Woo WS, Lee KR, Ma ES 1994. Analgesic,
29: 112-113, apud Chemical Abstracts 87: 15798m. anti-inflammatory and antiviral effects of melandrin
Joe B, Lokesh BR 1997. Prophylactic and therapeutic effects of derivatives. Yakhak Hoe Chi 38: 345-350.
polyunsaturated fatty acids, capsaicin, and curcumin Luo B, Kobayashi S, Kimura I, Kimura M 1991. Inhibitory
on adjuvant induced arthritis in rats. J Nutr Biochem effects on angiogenesis and pouch fluid exudation by
87: 397-407. aconite alkaloids in adjuvant-induced inflammation
Kaplan HR, Wolke RE, Malone MH 1967. Anti-inflammatory of the mouse. Phytother Res 5: 231-233.
evaluation of cryogenine. J Pharm Sci 56: 1385- Ma JJ, Si LF, Ding Y, Lin ZB, Chen XR, Han CL, Peng QS, Fang
1392. Y 1991. Inhibition of type I-IV allergic reactions by
Kasahara Y, Hikino H, Tsurufuji S, Watanabe M, Ohuchi K oxymatrine. Beijing Yike Daxue Xuebao 23: 445-
1985. Anti-inflammatory actions of ephedrines in 447.
acute inflammations. Planta Med 51: 325-331. McCarthy GM, McCarty DJ 1992. Effect of topical capsaicin in
Kimura M, Suzuki J, Yamada T, Yoshizaki M, Kikuchi T, the therapy of painful osteoarthritis of the hands. J
Rev. Bras. Farmacogn.
136 Braz J. Pharmacogn.
16(1):jan/mar. 2006
Anti-inflammatory activity of alkaloids A twenty-century review

Rhematol 19: 604-607. Berberidaceae family. Interrelation of chemical


Madan BR, Al-Motrefi A 1986. Anti-inflammatory actions of structure and pharmacological activity. Farmatsiya
some amino acids and their derivatives. IRCS Med (Moscow) 25: 33-38.
Sci 14: 288-285, apud Chemical Abstracts 104: Naik RG, Kattige SL, Bhat SV, Alreja B, De Souza NJ, Rupp RH
218520g. 1988. An antiinflammatory cum immunomodulatory
Malkinson FD 1982. Colchicine: new uses of an old, old drug. piperidinylbenzopyranone from Dysoxylum
Arch Dermatol 11: 453-457. binectariferum: isolation, structure and total
Mascolo N 1987. Biological screening of Italian medicinal synthesis.Tetrahedron 44: 2081-2086.
plants for anti-inflammatory activity. Phytother Res Nikolov R, Peneva M 1978. Study of analgesic and
1: 28-31. antiiflammatory action of glaucine. Eksp Med
Matsuda H, Tokuoka K, Shiomoto H, Kubo M 1997. Anti- Morfol 17: 190-194, apud Chemical Abstracts 91:
inflammatory activities of dehydrocorydaline 274w.
isolated from Corydalis tuber. Nat Med 51: 293- Noamesi BK, Bamgbose SOA 1983. Cryptolepine - A
297. pharmacological review. First Int Seminar
Matsuda H, Yoshikawa M, Ko S, Iinuma M, Kubo M 1998. Cryptolepine 41-51.
Antinociceptive and antiinflammatory activities Oletta SA 1964. New alkaloids from Holarrhena species.
of evodiamine and rutaecarpine Nat Med 52: 203- Patent-GB 948485, 6 pp.
208. Omaye ST, Kosersky DS, Malone MH 1972. Proc West
Mikami M, Kitahara M, Katano M, Ariki Y, Mimaki Y, Pharmacol Soc 15: 205-208.
Sashida Y, Yamazaki M, Yui S 1999. Suppressive Onai N, Tsunokawa Y, Suda M, Watanabe N, Nakamura K,
activity of lycoricidinol (narciclasine) against Sugimoto Y, Kobayashi Y 1995. Inhibitory effects
cytotoxicity of neutrophil-derived calprotectin, of bisbenzylisoquinoline alkaloids on induction of
and its suppressive effect on rat adjuvant arthritis proinflammatory cytokines, interleukin-1 and tumor
model. Biol Pharm Bull 22: 674-678. necrosis factor-alpha. Planta Med 61: 497-501.
Millaire A, Ducloux G 1992. Treatment of acute and recurrent Ono M 1994. Inflammation inhibitors containing cepharanoline
pericarditis with colchicine. Lancet 340: 1458- or berbamine. Patent-Japan Kokai Tokkyo Koho-06
1459. 211,661.
Mimura T, Maeda K, Hariyama H, Aonuma S, Satake M, Fujita Ono M, Tanaka N, Moriyasu T 1994a. Anti-inflammatory
T 1982. Studies on biological activities of melanin action of cepharanthine ointment ingredient
from marine animals. I. Purification of melanin from in experimental animals; studies for the acute
Ommastrephes bartrami Lesuel and its inhibitory inflammation. Ensho 14: 431-438, apud Chemical
activity on gastric juice secretion in rats. Chem Abstracts 122: 71610x
Pharm Bull 30: 1381-1386. Ono M, Tanaka N, Moriyasu T 1994b. Anti-inflammatory action
Molokhova LG, Suslina ML, Datskovskii SB, Figurkin BA of cepharanthine ointment ingredient in experimental
1973. Antiinflammatory effect of fumitory alkaloids. animals: Studies on chronic inflammation and TNF-
Tr Permsk Gos Med Inst 118: 26-28. alpha production. Ensho 14: 425-429.
Montanari AM, Fenical W, Lindquist N, Lee AY, Clardy J Oriowo MA 1982. Anti-inflammatory activity of piperonyl-
1996. Volutamides A-E, halogenated alkaloids with 4-acrylic isobutyl amide, an extractive from
atifeedant properties from the atlantic Bryozoan Zanthoxylum zanthoxyloides. Planta Med 44: 54-
Amathia convoluta.Tetrahedron 52: 5371-5380. 56.
Moon TC, Murakami M, Kudo I, Son KH, Kim HP, Kang SS, Otsuka H, Tsukui M, Matsuoka T, Goto M, Fujimura H,
Chang HW 1999. A new class of Cox-2 inhibitor, Hiramatsu Y, Sawada T 1974. Studies on anti-
rutaecarpine from Evoida rutaecarpa. Inflamm Res inflammatory agents. anti-inflammatory screening
48: 621-625. by fertile egg method. Yakugaku Zasshi 94: 796.
Morita G 1926. Antiinflammatory effect of drugs. Folia Jap Otsuka H, Fujimura H, Sawada T, Goto M 1981a. Studies on
Pharmacol 3: 233-244. anti-inflammatory agents. Part 2. anti-inflammatory
Munjudar AM, Dhuley JN, Deshmukh VK, Raman PH, Naik constituents from rhizome of Coptis japonica
SR 1990. Anti-inflammatory activity of piperine. Makino. Yakugaku Zasshi 101: 883-890.
Jpn J Med Sci Biol 43: 95-100, Chemical Abstracts Otsuka H, Fujioka S, Komiya T, Goto M, Hiramatsu Y,
114: 178024w. Fujimura H 1981b. Studies on anti-inflammatory
Murakoshi I, Fujii Y, Kawamura H, Maruyama H 1992. Lupine agents. Part 5. A new anti-inflammatory constituent
alkaloids as anti-inflammatory agents. Patent-Japan of Pyracantha crenulata Roem. Chem Pharm Bull
Kokai Tokkyo Koho-04 295,479, apud Chemical 29: 3099-3104.
Abstracts 119: 45773u. Otsuka H, Komiya T, Fujioka S, Goto M, Hiramatsu Y, Fujimura
Murayama M, Mori T, Bando H, Amiya T 1991. Studies on H 1981c. Studies on anti-inflammatory agents. Part
the constituents of Aconitum species. IX. the 3. An antiinflammatory constituent of the genus
pharmacological properties of pyro-type aconitine Acer. Yakugaku Zasshi 101: 1108-1112.
alkaloids, components of processed aconit powder Otsuka H, Fujioka S, Komeya T, Mizuta E, Takamoto M
‘kako-bushi-matsu’: analgesic, antiinflammatory 1982. Studies on anti-inflammatory agents. Part 6.
and acute toxic activities. J Ethnopharmacol 35: Anti-inflammatory constituents of Cinnamomum
159-164. sieboldii Meissn. Yakugaku Zasshi 102: 162-172.
Naidovich LP, Trutneva EA, Tolkachev ON, Vasil’eva VD 1976. Otsuka H, Hirai Y, Nagao T, Yamasaki K 1988. Anti-
Chemical composition of indigenous species of the inflammatory activity of benzoxazinoids from roots
Rev. Bras. Farmacogn.
Braz J. Pharmacogn.
137
16(1):jan/mar. 2006
José M. Barbosa-Filho, Márcia R. Piuvezam, Marcelo D. Moura, et al.

of Coix lachryma-jobi var. ma-yuen. J Nat Prod 51: 80578a.


74-79. Sadritdinov FS 1980. Pharmacological properties of alkaloids
Panthong A, Kanjanapothi D, Thitiponpunt Y, Taesotikul T, from a Berberis integerrima plant. Med Zh Uzb 2:
Arbain D 1984. Anti-inflammatory activity of the 54-55, apud Chemical Abstracts 92: 174599s.
alkaloid anabasamine. Dokl Akad Nauk Uzssr 198: Saeed SA, Simjee KU, Mahmood F, Rahman NN 1993.
45-47, apud Chemical Abstracts 102: 125224g. Dual inhibition of platelet-activating factor and
Panthong A, Kanjanapothi D, Thitiponpunt Y, Taesotikul T, arachidonic acid metabolism by ajmaline and effect
Arbain D 1998. Anti-inflammatory activity of the on carrageenan-induced rat paw oedema. J Pharm
alkaloid bukittinggine from Sapium baccatum. Pharmacol 45: 715-719.
Planta Med 64: 530-535. Saidkasymov T, Sultanov MB, Umarova SH 1971. Effect of the
Parmely MJ, Zhou WW, Edwards III CK, Borcherding DR, alkaloids edpetiline and petiline on the course of
Silverstein R, Morrison DC 1993. Adenosine and a experimental arthritis in rats. Farmakol Alkaloidov
related carbocyclic nucleoside analogue selectively Glikozidov 19: 187.
inhibit tumor necrossis factor-alpha production and Saidkasymov T 1978. Pharmacology of the alkaloid veralosine.
protect mice against endotox challenge. J Immunol Farmakol Prir Veshchestv 71-74.
151: 389-396. Sais G, Vidaller A, Jucgla A, Gallardo E, Peyri J 1995. Colchicine
Parnham MJ 1991. Drugs in inflammation. Birkhauser Verlag, in the treatment of cutaneous leukocytoclastic
Basel. vasculitis: results of a prospective, randomized
Perdue GP, Blomster RN, Blake DA, Farnsworth NR 1979. controled trial. Arch Dermatol 131: 1399-1402.
South American plants. II. Taspine, isolation and Saito H, Ueyama T, Naka N, Yagi J, Okamoto T 1982.
antiinflammatory activity. J Pharm Sci 68: 124- Pharmacological studies of ignavine, an Aconitum
126. alkaloid. Chem Pharm Bull 30: 1844-1850.
Persinos GJ 1972. Anti-inflammation compositions containing Saito H, Saito S, Okamoto T 1983. Ignavine as an analgesic,
taspine or acid salts thereof and method of use. antipyretic, and anti-inflammatory drug. Patent-
Patent-US-3,694,557. Japan Kokai Tokkyo Koho-58 42,923.
Pinto L, Borrelli F, Bombardelli E, Cristoni A, Capasso F 1998. Salama AM, Lopez MS, Gutierrez M, Achenbach H 1987.
Anti-inflammatory, analgesic and antipyretic effects Antinflammatory and cardio activie glucosides from
of glaucine in rats and mice. Pharm Pharmacol Sechium edule. Rev Latinoamer Quim 18: 132-133.
Commun 4: 502-505. Santos FA, Rao VSN 1998. Study of the anti-pyretic effect
Pitts JR 1995. Colchicine therapy for palmar fibromatosis. N of quinine, an alkaloid effective against cerebral
Engl J Med 333: 393. malaria, on fever induced by bacterial endotoxin
Plotnick S, Huppert AS, Kantor G 1989. Colchicine and and yeast in rats. J Pharm Pharmacol 50: 225-229.
leukocytoclastic vasculitis. Arthritis Rheumatism Sawynok J, Reid AR, Doak GJ 1995. Caffeine antiociception in
32: 1489-1490. the rat hot-plate and formalin tests and locomotor
Rao CH, Rao DV, Raju VSN, Sullivan BW, Faulkner DJ 1989. stimulation: involvement of nonadrenergic
Two new alkaloids from an Indian species of mechanisms. Pain 61: 203-213.
Zoanthus. Heterocycles 28: 103-106. Schinitsky MR 1980. Vinblastine in rheumatoid arthritis.
Raychaudhuri A, Colombo C, Pastor G, Wong M, Jeng AY Patent-US-4,208,414.
1991. Effect of capsaicin on carrageenan-induced Seow WK, Li ST-Ying, Thong YH 1986. Inhibitory effect of
inflammation in rat pleurisy and exudate substances tetrandrine on human neutrophil and monocyte
p level. Agents Actions 34: 251-253. adherence. Immun Lett 13: 83-88.
Reddy ACP, Lokesh BR 1994. Studies on anti-inflammatory Seow WK Ferrante A, Li SY, Thong YH 1988. Antiphagocytic
activity of spice principles and dietary n-2 and anti-oxidant properties of the plant alkaloid
polyunsaturated fatty acids on carrageenan-induced tetrandrine. Int Archs Allergy Appl Immun 85: 404-
inflammation in rats. Ann Nutr Metab 38: 349-358, 409.
apud Chemical Abstracts 122: 104726v. Seow WK, Ferrante A, Li SY, Thong YH 1989. Suppression
Revesz J, Bilkei-Gorzo A, Kormoczy PS 1992. The of human monocyte interleukin 1 production by the
antiinflammatory effect of therophylline. Pharmacol plant alkaloid tetrandrine. Clin Exp Immun 75: 47-
Res 25: 262-263. 51.
Rios JL, Giner RM, Villar A 1989. Isolation and identification Shin KH, Yun-Choi HS, Chung HS, Koo KA, Kim D 1996.
of an antiinflammatory principle from Santolina Antiinflammatory and analgesic effects of
chamaecyparissus. Phytother Res 35: 212-214. higenamine, a component of Aconiti tuber. Nat Prod
Sadritdinov F 1971. Comparative study of the antinflammatory Sci 21: 24-28.
properties of alkaloids from Gentiana plants. Somei M 1987. Processes for the preparation of (+)-paniculidine
Farmakol Alkaloidov Glikozidov 146-148. b as an analgesic or inflammation inhibitor. Patent-
Sadritdinov F, Sultanov MB 1971. Antiinflammatory activity Japan Kokai Tokkyo Koho-62 111,966, apud
of the alkaloids thalmine and O-methylthalieberine. Chemical Abstracts 108: 94825w.
Farmakol Alkaloidov Glikozidov 120. Sullivan BW, Faulkner DJ, Rao CB, Rao DV, Raju VSN 1991.
Sadritdinov F 1972. Antiinflammatory activity of fetidine. New alkaloids from an Indian species of Zoanthus.
Farmakol Alkaloidov Ikh Proizvod 154. Bioact Compd Mar Org Indo-Us Symp 219-224.
Sadritdinov FS 1974. Comparative pharmacological study of Sullivan P, Bekir S, Jaffar Z, Page C, Jeffery, Costello J
thalicsimine, tetrandrine, and demethyltetrandrine. 1994. Anti-inflammatory effects of low-dose oral
Med Zh Uzb 54, apud Chemical Abstracts 82: theophylline in atopic asthma. Lancet 343 (8904):
Rev. Bras. Farmacogn.
138 Braz J. Pharmacogn.
16(1):jan/mar. 2006
Anti-inflammatory activity of alkaloids A twenty-century review

1006-1008. Comparative effects of tetrandrine and berbamine


Sung CY, Chi HC, Liu KT 1958. The Pharmacology of on subcutaneous air pouch inflammation induced by
gentianine. I. Antiphlogistic effect and acion of interleukin 1, tumour necrosis factor and platelet-
pituitary-adrenal function of the rat. Sheng Li Hsueh activating factor. Agents Actions 36: 112-118.
Pao 22: 201-205. Wu YC, Uw TS, Niwa M, Lu ST, Hirata Y, Mc Phail DR, Mc Phail
Suzuki S, Kishi S, Nakasako T, Ohyanagi Y 1983. Anti- AT, Lee KH 1988. Structure and stereochemistry
inflammatory effects of polyamines. Ensho 34: of thalicsiline, a new antiinflammatory C-20
409-410. diterpenoid alkaloid from Thalictrum sessile.
Svoboda GH, Kattau RW 1967. Alkaloids of Acronychia Heterocycles 27: 1813-1816.
baueri (Bauerella australiana) III. CNS depressant Yamahara J, Sawada T, Kozuka M, Fujimura H 1974a.
principles. Lloydia 30: 364-371. Pharmacological actions of the alkaloids of
Takahashi H, Shiraishi A, Iizuka Y, Furuya K, Kagasaki T 1992. Menispermaceous plants. I. Pharmacological
Manufacture of anticancer and anti-inflammatory actions of tetrandrine. Shoyakugaku Zasshi 28: 83-
apiodionen with apiosordaria. Patent-Japankokai 95, apud Chemical Abstracts 83: 53481c.
Tokkyo Koho-04 49,289. Yamahara J, Sawada T, Fujimura H 1974b. Pharmacological
Takigawa M, Miyachi Y, Uehara M, Tagami H 1982. Treatment actions of the alkaloids of Menispermaceous
of pustulosis palmaris et plataris with oral doses of plants. II. Pharmacological actions of trilobine and
colchicine. Arch Dermatol 118: 458-460 isotrilobine. Shoyakugaku Zasshi 28: 96-101, apud
Tan H, Zhang B 1985. An experimental study of matrine‘s anti- Chemical Abstracts 83: 53482d.
hypertensive effect. Chin J Integ Trad West Med 5: Yamamoto S, Kiyoto I, Aizu E, Nakadate T, Hosoda Y, Kato
108-110. R 1989. Differential inhibition by staurosporine,
Tang XC, Lin ZG, Cai W, Chen N, Shen L 1984. Antiinflammatory a potent protein kinase c inhibitor, of 12-O-
effect of 3-acetylaconitine. Chung-Kuo Yao Li tetradecanoylphorbol-13-acetate-caused skin tumor
Hsueh Pao 5: 85-89, apud Chemical Abstracts 101: promotion epidermal ornithine decarboxylase
17013b. induction, hyperplasia and inflammation.
Teh BS, Ioannoni B, Seow WK, McCormack JG, Thong YH Carcinogenesis 10: 1315-1322.
1989. Supresion by tetrandrine of human platelet Yamasaki H, Saeki K 1967. Inhibition of mast-cell degranulation
aggregation induced by platelet-activating factor by anti-inflammatory agents. Arch Int Pharmacodyn
and othe stimulants. Int Archs Allergy Appl Immun Ther 105: 166, apud Chemical Abstracts 67:
88: 267-272. 72108x.
Teh BS, Seow WK, Li SY, Thong YH 1990. Inhibition of Yang JJ, Yu DQ 1990. Synthesis of ganoderma alkaloid A and B.
prostaglandin and leukotriene generation by the Yao Hsueh Hsueh Pao 25: 555-559, apud Chemical
plant alkaloids tetrandrine and berbamine. Int J Abstracts 114: 164574p.
Immunopharmac 12: 321-326. Yasukawa K, Takido M, Ikekawa T, Shimada F, Takeuchi
Tits M, Damas J, Quetin-Leclercq J, Angenot L 1991. From M, Nakagawa S 1991. Relative inhibitory
ethnobotanical uses of Strychnos henningsii to activity of berberine-type alkaloids against 12-
antiinflammatories, analgesics and antispasmodics. o-tetradecanoylphorbol-13-acetate-induced
J Ethnopharmacol 34: 261-267. inflammation in mice. Chem Pharm Bull 39: 1462-
Tulyaganov N, Sadritdinov F 1971. Seasonal fluctuations in the 1465.
activity of antiinflammatory substances. Farmakol Yasukawa K, Akasu M, Takeuchi M, Takido M 1993.
Alkaloidov Glikozidov:125. Bisbenzylisoquinoline alkaloids inhibit tumor
Ulrichova J, Walterova D, Simanek V 1984. Molecular promotion by 12-O-tetradecanoylphorbol-13-
mechanisms of the biological activity of quaternary acetate in two-stage carcinogenesis in mouse skin.:
benzophenanthridine and protoberberine alkaloids. Oncology 50: 137-140.
Acta Univ Palacki Olomuc Fac Med 106:31-37, Yoshino S, Blake DR, Bacon PA 1984. The effect of
apud Chemical Abstracts 102: 1a. desferrioxamine on antigen-induced inflammation
Wang M, Huang YJ, Zhang TH, Tong ZQ 1996. Anti-allergic, in the rat air pouch. J Pharm Pharmacol 36: 543-
anti-histamine and anti-inflammatory effects of 545.
compound pseudoephedrine. Shenyang Yaoke Zhang DH, Li HY, Sang WL 1982. Studies on constituents of
Daxue Xuebao 132:129-133. fu zi (Aconitum carmichaeli). A traditional chinese
Willenborg GO, Cowden DB, Parish CR 1990. Use of medicine. II. Chemical constituents of a processed a
castanospermine as an anti-inflammatory and carmichaeli, bai fu pian. Chung Ts’ao Yao 13: 481-
immunosuppressant agent. Patent-Pct Int Appl-90 484.
01,319, apud Chemical Abstracts 114: 35993a. Zhang J 1985. Yuoxue Xuebao 20: 423, apud Chemical Abstracts
Willianson EM 1996. Selection, preparation and 105: 9093o.
pharmacological evaluation of plant material. John Zhang MF, Shen YQ, Tang CK 1990. Anti-inflammatory and
Wiley and Sons. Chichester, Eng. analgesic actions of berberine. Tianran Chanwu
Wong CW, Seow WK, Zeng TS, Halliday JJ, Thong YH 1991. Yanjiu Yu Kaifa 21: 49-53, apud Chemical Abstracts
Comparative immunopharmacology and toxicology 115: 197979y.
of the bisbenzylisoquinoline alkaloids tetrandrine
and berbamine. Int J Immunopharmacol 13: 579-
585.
Wong CW, Seow WK, O’callaghan JW, Thong YH 1992.
Rev. Bras. Farmacogn.
Braz J. Pharmacogn.
139
16(1):jan/mar. 2006

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