Protective effect of Cissus quadrangularis on neutrophil mediated tissue injury induced by aspirin in rats.

Abstract

Cissus quadrangularis (family: Vitaceae) is well known for the treatment of gastric disorders in traditional medicine, owing to its rich source of carotenoids, triterpenoids and ascorbic acid, and has received considerable attention regarding its role in human nutrition. In the search of new potential antiulcer agents, the present study evaluated the ethanol extract of Cissus quadrangularis (CQE) against the gastric toxicity induced by aspirin in rats. The optimum protective dose of 500 mg/kg of extract was selected by the pretreatment of gastric ulcers with different doses of CQE (250, 500 and 750 mg/kg) for 7 days which showed ulcer protection by 40, 71.2 and 72.6%, respectively, as compared to ranitidine (RTD) (30 mg/kg) by 71.9% in the aspirin model. In addition, results have shown that administration of aspirin increases lipid peroxidation status, xanthine oxidase (XO), myeloperoxidase and decrease in selenium-glutathione peroxidase activities in the gastric mucosa, resulting in mucosal damage at both cellular and subcellular level. Pretreatment with CQE ameliorated the observed effect significantly in the gastric mucosa of ulcerated rats. These findings suggest that the gastroprotective activity of CQE could be mediated possibly through its antioxidant effect as well as by the attenuation of the oxidative mechanism and neutrophil infiltration.

Full text

Page 1

Journal of Ethnopharmacology
Journal of Ethnopharmacology
Volume 104, Issue 3, Pages 295-434 (6 April 2006)
01
A role for physicians in ethnopharmacology and drug discovery • DISCUSSION Pages 297-301 Mohsin Raza
02
Protective effect of Cissus quadrangularis on neutrophil mediated tissue injury induced by aspirin in rats • ARTICLE
Pages 302-305 Mallika Jainu, K. Vijai Mohan and C.S. Shyamala Devi
03
Anti-diabetic activity of methanol/methylene chloride stem bark extracts of Terminalia superba and Canarium schweinfurthi
on streptozotocin-induced diabetic rats • ARTICLE Pages 306-309 P. Kamtchouing, S.M. Kahpui, P.-D. Djomeni Dzeufiet,
L. Tédong, E.A. Asongalem and T. Dimo
04
Anti-inflammatory and antinociceptive activities of Seseli L. species (Apiaceae) growing in Turkey • ARTICLE
Pages 310-314 Esra Küpeli, Alev Tosun and Erdem Yesilada
05
Effects of Urginea sanguinea, a traditional asthma remedy, on embryo neuronal development • ARTICLE Pages 315-321 J.
Marx, E. Pretorius and M.J. Bester
06
Antioxidant activity of Nelumbo nucifera (sacred lotus) seeds • ARTICLE Pages 322-327 Sujay Rai, Atul Wahile, Kakali
Mukherjee, Bishnu Pada Saha and Pulok K. Mukherjee
07
Nitric oxide-dependent vasorelaxation induced by extractive solutions and fractions of Maytenus ilicifolia Mart ex Reissek
(Celastraceae) leaves • ARTICLE Pages 328-335 Yanna D. Rattmann, Thales R. Cipriani, Guilherme L. Sassaki, Marcello
Iacomini, Lia Rieck, Maria C.A. Marques and José E. da Silva-Santos
08
Mechanisms of the vasorelaxant effect of Danshen (Salvia miltiorrhiza) in rat knee joints • ARTICLE Pages 336-344
F.Y. Lam, S.C.W. Ng, J.H.Y. Cheung and J.H.K. Yeung
09
Puerariae radix promotes differentiation and mineralization in human osteoblast-like SaOS-2 cells • ARTICLE
Pages 345-350 Jeong-Eun Huh, Ha-Ru Yang, Dong-Suk Park, Do-Young Choi, Yong-Hyeon Baek, Eun-Mi Cho, Yoon-Je
Cho, Kim Kang-Il, Deog-Yoon Kim and Jae-Dong Lee
10
Antihypertensive and vasodilator effects of methanolic and aqueous extracts of Tribulus terrestris in rats • ARTICLE
Pages 351-355 Oludotun A. Phillips, Koyippalli T. Mathew and Mabayoje A. Oriowo
11
Action of Hygrophila auriculata against streptozotocin-induced oxidative stress • ARTICLE Pages 356-361
M. Vijayakumar, R. Govindarajan, G.M.M. Rao, Ch.V. Rao, A. Shirwaikar, S. Mehrotra and P. Pushpangadan
12
Effect of anemonin on NO, ET-1 and ICAM-1 production in rat intestinal microvascular endothelial cells • RTICLE
Pages 362-366 Huiqin Duan, Yongdong Zhang, Jianqin Xu, Jian Qiao, Zhanwei Suo, Ge Hu and Xiang Mu
13
Antihyperglycemic effect of the fruit-pulp of Eugenia jambolana in experimental diabetes mellitus • ARTICLE
Pages 367-373 Suman Bala Sharma, Afreena Nasir, Krishna Madhava Prabhu and Pothapragada Suryanarayana Murthy

Page 2

14
Huperzia saururus, activity on synaptic transmission in the hippocampus • ARTICLE Pages 374-378 M.G. Ortega, M.G.
Vallejo, J.L. Cabrera, M.F. Pérez, R.S. Almirón, O.A. Ramírez and A.M. Agnese
15
Tissue lipid lowering-effect of a traditional Nigerian anti-diabetic infusion of Rauwolfia vomitoria foilage and Citrus
aurantium fruit • ARTICLE Pages 379-386 Joan I.A. Campbell, Alicja Mortensen and Per Mølgaard
16
The botanical materia medica of the Iatrosophikon—A collection of prescriptions from a monastery in Cyprus • ARTICLE
Pages 387-406 Andreas Lardos
17
Chemoprevention and cytotoxic effect of Bauhinia variegata against N-nitrosodiethylamine induced liver tumors and human
cancer cell lines • SHORT COMMUNICATION Pages 407-409 B. Rajkapoor, B. Jayakar, N. Murugesh and D.
Sakthisekaran
18
Anti-inflammatory activity of Trichodesma indicum root extract in experimental animals • SHORT COMMUNICATION
Pages 410-414 James B. Perianayagam, S.K. Sharma and K.K. Pillai
19
Lepidium meyenii (Maca) does not exert direct androgenic activities • SHORT COMMUNICATION Pages 415-417 P.
Bogani, F. Simonini, M. Iriti, M. Rossoni, F. Faoro, A. Poletti and F. Visioli
20
Screening of plants used in Danish folk medicine to treat memory dysfunction for acetylcholinesterase inhibitory activity •
SHORT COMMUNICATION Pages 418-422 Anne Adsersen, Bente Gauguin, Lene Gudiksen and Anna K. Jäger
21
Free radical scavenging potential of Chlorophytum tuberosum baker • SHORT COMMUNICATION Pages 423-425
Sreevidya Narasimhan, Raghavan Govindarajan, Madhavan Vijayakumar and Shanta Mehrotra
22
Protective effect of bioactive fraction of Sphaeranthus indicus Linn. against cyclophosphamide induced suppression of
humoral immunity in mice• SHORT COMMUNICATION Pages 426-429 A.R. Bafna and S.H. Mishra

Page 3

Journal of Ethnopharmacology 104 (2006) 297–301
Commentary
A role for physicians in ethnopharmacology and drug discovery
Mohsin Raza∗
Department of Physiology, School of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-111, Tehran, Iran
Received 27 October 2005; received in revised form 8 January 2006; accepted 10 January 2006
Available online 3 February 2006
Abstract
Ethnopharmacology investigations classically involved traditional healers, botanists, anthropologists, chemists and pharmacologists. The role
of some groups of researchers but not of physician has been highlighted and well defined in ethnopharmacological investigations. Historical data
showsthatdiscoveryofseveralimportantmoderndrugsofherbaloriginowetothemedicalknowledgeandclinicalexpertiseofphysicians.Current
trends indicate negligible role of physicians in ethnopharmacological studies. Rising cost of modern drug development is attributed to the lack of
classical ethnopharmacological approach. Physicians can play multiple roles in the ethnopharmacological studies to facilitate drug discovery as
well as to rescue authentic traditional knowledge of use of medicinal plants. These include: (1) Ethnopharmacological field work which involves
interviewing healers, interpreting traditional terminologies into their modern counterparts, examining patients consuming herbal remedies and
identifying the disease for which an herbal remedy is used. (2) Interpretation of signs and symptoms mentioned in ancient texts and suggesting
proper use of old traditional remedies in the light of modern medicine. (3) Clinical studies on herbs and their interaction with modern medicines.
(4) Advising pharmacologists to carryout laboratory studies on herbs observed during field studies. (5) Work in collaboration with local healers
to strengthen traditional system of medicine in a community. In conclusion, physician’s involvement in ethnopharmacological studies will lead to
more reliable information on traditional use of medicinal plants both from field and ancient texts, more focused and cheaper natural product based
drug discovery, as well as bridge the gap between traditional and modern medicine.
© 2006 Elsevier Ireland Ltd. All rights reserved.
Keywords: Physician; Ethnopharmacology; Traditional medicine; Drug discovery
1. Introduction
Ethnopharmacology provides an opportunity for both mul-
tidisciplinary and interdisciplinary scientific collaboration
between the investigators of botany, pharmacology and toxi-
cology, chemistry, anthropology and sociology (Schultes, 1962;
Malone, 1983; Sandberg, 1987; Verpoorte, 1989; Etkin, 1993).
Ethnopharmacologic exploration, involving both field visits, as
well as experimental research has lead in past to highly valuable
informationaboutmedicinalplantsusedindifferentculturesand
many were developed into drugs (Bruhn and Holmstedt, 1981;
Holmstedt, 1991; Fabricant and Farnsworth, 2001).
Physicians by their training are exposed to several disci-
plines of science relevant to ethnopharmacological investiga-
tions. Indeed, the need for physicians as an active member of
ethnopharmacological team has been felt in the past and fail-
∗Tel.: +98 21 88011001x3577; fax: +98 21 88013030.
E-mail address: mohsinrazahej@yahoo.com.
ures and limitations have been attributed due to the lack of their
participation (Weniger, 1991; Anonymous, 1993; Farnsworth,
1994; Lozoya, 1994; Cordell and Colvard, 2005). However, no
clear role or scope of activities is defined for physicians. This
articlediscussestherolephysicianscouldplayinvariousaspects
of ethnopharmacological research and discovery of drugs based
on traditional knowledge.
2. Historical background
Enormousethnopharmacologicalresearchwascarriedoutby
physicianswithexpertiseorinterestinchemistry,pharmacology,
botany or anthropology during the early period of medicinal
plant research 250 years ago. The classic example is of Dr.
William Withering, who in 1775 discovered the use of foxglove
in the treatment of ‘dropsy’ (i.e. edema) due to cardiac ailment
(now known as congestive heart failure). The plant was used for
the cure of ‘dropsy’ in the form of aqueous tea of 20 or more
herbs by an old woman in Shropshire. Withering combined his
medical expertise and knowledge of botany and discovered that
0378-8741/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.jep.2006.01.007

Page 4

298
M. Raza / Journal of Ethnopharmacology 104 (2006) 297–301
Table 1
Selected physicians and their contributions in ethnopharmacological investigations
Willem Pies (1611–1678)
William Withering (1741–1799)
Robert Christison (1797–1882)
John Hutton Balfour (1808–1884)
Claude Bernard (1813–1878)
Paolo Mantegazza (1831–1910)
John Kirk (1832–1922)
Symphronio Olympio Cezar Coutinho (1832–1887)
Douglas Argyll Robertson (1837–1909)
Thomas Richard Fraser (1841–1920)
Nagai Nagayoshi (1844–1929)
John Raleigh Briggs (1851–1907)
Arthur Heffter (1860–1925)
Thomas Moreno Y Maiz (1868)a
Medicinal uses of Pilocarpus jaborandi
Use of Foxglove in “Dropsy” (congestive heart failure)
Toxicology of Physostigma venenosum
Description of Physostigma venenosum
Pharmacological investigation of curare
Medicinal uses of coca
Effect of African arrow poison (Strophanthus sp.) on CVS
Investigation of medicinal uses and introduction of Pilocarpus jaborandi in medical practice
Introduction of Physostigma venenosum in ophthalmic medicine
Pharmacology of Physostigma venenosum
Chemistry and pharmacology of ephedrine
Investigation of peyote
Chemistry and pharmacology of peyote alkaloids
Pharmacological investigation of cocaine
For more details see: Aronson (1987), Holmstedt (1972, 1991), Holmstedt et al. (1979), Holmstedt and Fredga (1981) and Heinrich and Gibbons (2001).
aYear of completion of thesis.
foxglove was the active ingredient, and that only dropsy related
to heart ailment was curable (Aronson, 1987).
Several investigators (Table 1) who played leading role in
the discovery and/or use of physostigmine, cocaine, ephedrine,
emetine, pilocarpine, strychnine, etc. from traditional sources
werephysicians(Holmstedt,1972,1991;Holmstedtetal.,1979;
Holmstedt and Fredga, 1981; Heinrich and Gibbons, 2001).
These physicians while working with experts from other disci-
plines performed several roles, from field studies during explo-
rations, to working both as botanists and anthropologists to
conducting lab experiments as chemists and pharmacologists.
With the advancement of synthetic approaches in recent
years, there has been a general lack of classical ethnophar-
macological approaches in medicinal plant research both as a
source of lead compounds for new drugs as well as in published
research (Etkin, 2001; Cordell and Colvard, 2005). For several
years there has also been reduced collaboration between differ-
ent disciplines and clinicians that has contributed to a decline in
the number of new drugs (Farnsworth et al., 1985; Tyler, 1986;
Anonymous, 2002). Due to public reliance on traditional thera-
pies and use of herbal products, the curricula in some countries
have been recently modified (Giordano et al., 2002) and conse-
quently physicians are becoming more familiar with concepts
and practices of traditional medicine systems. In the future they
mayservetointegrateand‘translate’traditionalknowledgeinto
modern medicine.
3. Areas of ethnopharmacological studies where a
physician could contribute
3.1. Ethnopharmacological field work
Field observations of traditional therapies are of pivotal
importance for investigating their pharmacological effects in
humans and isolating their active principles (Holmstedt and
Bruhn, 1982). A physician can carry out field observation of
pharmacological effects of traditional therapies in humans with
precision (Holmstedt and Bruhn, 1982), which in turn could
guide a pharmacologist working in a lab.
3.1.1. Interviewing traditional healers and interpretation of
traditional concepts
Interviewing traditional healers for accurate information
aboutherbalrecipes,theircomponentherbs,theirmedicinaland
other uses constitutes an important activity in ethnopharmaco-
logical field investigation (Lipp, 1989). A major problem has
been the translation of indigenous diseases or concepts of ill-
ness into their modern counterparts and vice versa (Cox, 1994).
Description of a disease and its diagnostic criteria, signs, symp-
toms, treatment, dosage schedule and its progress (Table 2) are
all to be noted by the field worker (Lipp, 1989). Commonly,
confusion in data interpretation occurs when information about
an illness is obtained in the field by a non-physician, such as
an ethnobotanist, biologist, anthropologist or even a trained
interviewer (Lewis and Elvin-Lewis, 1994; Lozoya, 1994). For
example, a mere description of fever, pain at any site, tremor,
skin lesion, fainting, or edema can be interpreted as various
illnesses. (I have personally experienced how difficult it is to
interpretheardorwritteninformationfromanon-physicianfield
worker due to crucial missing data which could point to a spe-
cific illness.) Up to 35% of diseases remain undiagnosed when
a traditional healer is interviewed by a non-physician worker
in the field (Cox, 1994) and essential information is lost only
because physicians were not involved.
New medical discoveries and advancement of associated
technology is further widening the gap between traditional con-
cepts of diseases, their treatment by healers and the present day
physicians. A physician interested in ethnopharmacology could
fill this gap and offer modern explanation of old concepts of
healing. However, all this requires a modest and collaborative
attitude of physicians with healers, botanists and anthropolo-
gists which the key to successful acquisition of the information
(Lozoya, 1994).
For various reasons, it may be difficult to get information on
medicinal uses of plants from healers which could later be used
in biomedical research (Malone, 1983). Direct observations by
physician (vide Table 2 for summary) may reduce the need of
cross-checking information obtained from one healer or using
different interviewing techniques.

Page 5

M. Raza / Journal of Ethnopharmacology 104 (2006) 297–301
299
Table 2
Activities that a physician could perform in ethnopharmacological field work
(adopted from Lipp (1989))
Physician’s role in ethnopharmacology field work
1. General idea about diseases prevalent in a particular area by direct
observation of geographical features of the area and landscape, people,
living conditions, food, sanitation, etc. and informal interview of
translator, local residents or contacts
2. Interviewing the healer and watching her/him treating an illness
3. Interpretation of information obtained from interview and visual
observation
a. Traditional concepts of disease terms
b. Diagnostic criteria used by healer
c. Etiology of illness
d. Signs and symptoms of illness
e. Treatment prescribed, its route of administration, dosage, mode of
effectiveness and total duration with different phases
f. Dietary, sexual or other restrictions
g. Side-effects or contraindications
h. Association with any rituals
i. Social restrictions related to age, sex, class, etc.
j. Whether treatment is prohibited in certain individuals and reason for it
k. Beliefs or myths or other views associated with disease or its specific
treatment with the plant
4. Examination of patient and diagnosis of illness
a. History taking
b. Physical Examination and routine test
c. Diagnosis of illness
d. Follow up
e. Result/s of treatment whether effective or otherwise
5. Analysis and verification of ‘heard’ verses ‘seen’ information collected
from healer, other team members and personal observation
6. Recording information (by means of photographs or video camera)
regarding signs, symptoms of illness, administration of an herbal
treatment and effects of treatment
A physician can comprehend the nature of illness and effec-
tiveness of its treatment, even if the information is translated
from another language. While opening the conversation with a
healer, the physician could ask about common health problems
in the area and have an idea as to the type of diseases or symp-
tomsprevalentbeforeactuallytalkingaboutaspecificcondition.
He can interpret physical signs and symptoms described by the
healer that point either to a systemic illness or a functional one.
Aphysician,byaskingfewrelevantquestions,canformanopin-
ionaboutthenatureofdiseaseandeffectivenessoftheherbused
to treat it.
3.1.2. Medical history, examination and diagnosis of
patients treated by healers
If allowed to take a medical history and examine a patient
being treated by the healer, a physician, by asking few key
questions, and with the help of simple paraphernalia (such as
stethoscope, blood pressure apparatus, otoscope, ophthalmo-
scope, thermometer and the like that can be easily carried in
a brief case) can make a diagnosis. Unlike in the remote past,
several ‘dipstick’ tests are now available to facilitate rapid diag-
nosis. This is particularly important as many traditional healers
are not accustomed to diagnosing disorders where detection of
sign and symptoms requires an apparatus or test. An example
is ‘frightening syndrome’ popular in the South American Jivaro
community, which is characterized by shortness of breath. A
physicianbysimpleexaminationandfewquestionscouldeasily
determine if this is due to respiratory, cardiac or psychological
causes (Lewis and Elvin-Lewis, 1994). He can also differen-
tially diagnose the disease or pathological state if the accurate
diagnosis is not possible, limiting it to few specific diseases.
Improvement in the patient’s condition allows her/him to give
a reasonable explanation of the site of action of the herb and
also the nature of illness. For example, if a definite viral illness
is cured by a herb, this indicates possible presence of antiviral
substances in it or, if a patient had disease symptoms due to
hypertension, a reduction in blood pressure or diuresis point to
a probable site of action or exclude others.
3.2. Systematic study and scrutiny of ancient traditional
literature
Many signs and symptoms described in ancient texts apply
very well to modern day’s clinical medicine. Advancement of
scienceandtechnologyhasaddednewterminologiesandmicro-
scopic depth to human observation, particularly in relation to
diagnosis of illness. However, visual observation by the naked
eyes has not changed. Rather, ancient healers and traditional
medicine systems relied more on direct observation of disease
symptoms and signs. These were observed in more depth and
detail,withoutanysupportfrominstrumentsorequipmentatthat
time and relying only on interpretation of information obtained
throughfivesenses.Inaddition,asopposedtomodernmedicine
whichreliesmoreonlaboratoryinvestigations,inpast,therewas
emphasis on a patient’s medical history. Thus, going through
ancient texts, one finds more graphic description of diseases
and conditions which makes the task of a researching physician
much easier to predict diagnoses or at least broadly categorize a
condition for which herb/s or recipes mentioned in ancient texts
were used.
An enormous amount of ancient literature from Greek and
Latin medical texts, pre-modern Western medicine, Chinese
medicine, Ayurveda and Unani medicine needs to re-examined
inthelightofmodernmedicalknowledge(Holland,1994;Tunon
and Bruhn, 1995; Buenz et al., 2004). It could be very cost
effective if a few plants from ancient medical texts are cho-
sen for targeted pharmacological study. Physicians by carefully
scrutinizing ancient literature for the signs and symptoms for
which a particular herb or herbs were used in the past in one
or more systems of medicine, can actually diagnose or at least
establish a probable diagnosis in many cases. Several disorders
present as syndromes that have three or more signs and symp-
tomsinapatientwhichcouldbeeasiertorecognizeifaphysician
can interpret the terms used in old texts in the light of modern
medicine. A recent example is the description of clinical signs
of a condition known as Kampavata (Kampa is tremor and vata
isresponsibleforallmovementsandsensationsincludingmotor
actions) in ancient Ayurveda text which resembles Parkinson’s
disease (Manyam and Sanchez-Ramos, 1999).
Information related to ethnomedical knowledge and scien-
tific research on medicinal plants is now available in the form
of databases. However, such databases have their own limi-