Content uploaded by Nikhil Gaikwad
Author content
All content in this area was uploaded by Nikhil Gaikwad on Aug 13, 2020
Content may be subject to copyright.
Review
Ethanopharmacology, phytochemistry and pharmacology of medicinally
potent genus Swertia:Anupdate
P.R. Kshirsagar
a,
⁎
,1
,U.B.Jagtap
b,1
,N.B.Gaikwad
c
,V.A.Bapat
a
a
Department of Biotechnology, Shivaji University, Kolhapur 416004, Maharashtra, India
b
Department of Botany, Government Vidarbha Institute of Science and Humanities, Amravati 444604, Maharashtra, India
c
Department of Botany, Shivaji University, Kolhapur 416004, Maharashtra, India
abstractarticle info
Article history:
Received 11 February 2019
Received in revised form 18 May 2019
Accepted 26 May 2019
Available online 21 June 2019
Edited by V Kumar
Swertia is a diverse genus of herbsbelongingto the family Gentianaceaeand comprisingroughly 170speciesdistrib-
uted throughout the world, but is most diversein temperate and subtropical regions and in montane tropics. In
Bhutan, China, India, Japan, and Nepal, some Swertia species are recognized for their anthelmintic, anti-
inflammatory,activity,finding use intraditionalmedicineto treat malariafever, liverdiseases,gastric trouble, jaun-
dice,diabetes,hepatitis, and otherailments. Theaim of the presentreviewis to provideupdated andcomprehensive
information on the genusSwertia, for promotin the development and uses of such ethnomedical resources.
Swertia species have been used in Indian traditional medical systems, the traditional Chinese system, and tradi-
tional Tibetan folk medicine for treating various ailments. In China, it has also been used as medicinal herbs for
treating hepatitis, cholecystitis, pneumonia, osteomyelitis, dysentery, and scabies. Broad spectrums of phyto-
chemicals such as xanthonoids, iridoids/secoiridoids, flavonoid, alkaloids, and terpenoids have been identified
from Swertia spp. The crude extracts and isolated metabolites from Swertia spp. exhibited a wide range of
in vitro and in vivo biological and pharmacological activities, including anticancer, anti-diabetic, antibacterial, an-
tioxidant, anti-hepatitis, anthelmintic, anti-leishmanial, neuroprotective, anticonvulsant, anxiolytic, hepatopro-
tective, gastric emptying and gastrointestinal motility, inhibitors of 5α-reductase, β-glucuronidase inhibitory,
anti-Benign prostatic hyperplasia and anti-mutagenic activities.
The extensiveliterature surveyreveals that Swertia species have beenused for medicinal purposein various parts
of the world and there is significant traditional evidence of their uses. Additional research is required targeting
individual ingredients responsible for the pharmacological effects, elucidating its mechanisms of action as well
as safety and toxicological assessment.
© 2019 SAAB. Published by Elsevier B.V. All rights reserved.
Keywords:
Biological activity
Phytochemistry
Pharmacology
Swertia
Toxicity study
Contents
1. Introduction.............................................................. 445
2. Methods................................................................ 447
South African Journal of Botany 124 (2019) 444–483
Abbreviations: 5-HT, 5-hydroxytr yptamine; AAP, acetaminophen; ABTS-2,2', azino-bis(3-ethylbenzoth iazoline-6-sulphonic acid); ALP, alkaline phosphatase; ALT, alanine
aminotransferase; ANIT, alpha-naphthylisot hiocyanate; AR, androgen receptor; AST, aspartate aminotransferase; AST, aspartate aminotransferase; b.w., body weight; Bax, Bcl-2-associ-
ated X protein; Bcl-2,B-cell CLL/lymphoma (Bcl)-2;BDL, bile duct ligated; bFGF, basicfibroblast growthfactor; BPH, benignprostatic hyperplasia; CA, cholic acid; CC
50
, 50% cytotoxic con-
centration; CCl
4
, carbontetrachloride;CDCA, chenodeoxycholic acid;DCA, deoxycholic acid; DMBA, dimethylbenz(a)anthracene;DPPH-1,1, diphenyl-1-picrylhydrazyl or2,2- diphenyl-1-
picrylhydrazyl; DTH, dichloromethane; EGF, epidermal growth factor; EMT, epithelial–mesenchymal transition; ER, estrogen receptor (ER); ETH, ethanol; GC-MS, gas chromatography
mass spectrometry; GOT, glutamate oxaloacetate transaminase; GPT, glutamate pyruvate transaminase; GPx, glutathione peroxidase; GSH, gluthathione; Gy, gray; H
2
O
2
, hydrogen per-
oxide; HBV,anti-hepatitisB virus; HDL, high density lipoprotein cholesterol;Hep G 2.2.15 cell, humanhepatocellularcarcinoma; HIF, hypoxia-inducible factor; HPLC,high pressure liquid
chromatography; I.p., intraperitoneal; IC
50
, inhibitory concentration 50%; IZD, inhibition zone diameter; LC, MS-Liquid chromatography mass spectrometry; LDL, low density lipoprotein
cholesterol; LOP, lipid peroxides; MIC, minimum inhibitory concentration; MTD, maximum tolerated dose; MTT, 3-(4,5-dimethylthiazol-2-yl), 2,5-diphenyltetrazolium bromide; NDEA,
N-nitrosodiethylamine; PC12 cell, The adrenal phaeochromocytoma cell line isolated from a tumor in the adrenal medulla of a rat; PCNA, proliferating cell nuclear antigen; SCMeOH,
Swertia corymbosa methanolic extract; SOD, superoxide dismutase; STZ, streptozotocin; TBA, total bile acid; TC, total cholesterol; TG, triglyceride; TIXS, total iridoids and xanthones;
TNFα, tumor necrosis factor alpha; Tα/βMCA, tauro-alpha/-beta-muricholic acid; VEGF, vascular endothelial growth factor.
⁎Corresponding author.
E-mail address: nbgaikwadsuk@gmail.com (P.R. Kshirsagar).
1
Both authors contributed equally to this manuscript.
https://doi.org/10.1016/j.sajb.2019.05.030
0254-6299/© 2019 SAAB. Published by Elsevier B.V. All rights reserved.
Contents lists available at ScienceDirect
South African Journal of Botany
journal homepage: www.elsevier.com/locate/sajb
3. Ethnobotany.............................................................. 447
3.1. Taxonomyandgeneralbotanicalaspects.............................................. 447
3.2. Historyandtraditionaluses.................................................... 447
4. Phytochemistry............................................................. 451
5. Biologicalactivities........................................................... 451
5.1. Antioxidantactivity ....................................................... 451
5.2. Antibacterialactivity....................................................... 452
5.3. Anthelminticactivity....................................................... 452
5.4. Antidiabeticactivity....................................................... 452
5.5. Anticonvulsantactivity...................................................... 452
5.6. Anxiolyticproperties....................................................... 453
5.7. Antihepatitisactivity....................................................... 458
5.8. Hepatoprotectiveeffect...................................................... 458
5.9. Neuroprotectiveactivity..................................................... 462
5.10. Anticanceractivity ....................................................... 462
5.11. Effectongastricemptyingandgastrointestinalmotility....................................... 463
5.12. Anti-leishmanialactivity..................................................... 463
5.13. Inhibitors of 5α-reductaseactivity................................................ 463
6. β-glucuronidaseinhibitoryactivity.................................................... 463
6.1. Anti-mutagenicactivity...................................................... 470
6.2. Anti-benignprostatichyperplasiaactivity ............................................. 473
7. Toxicitystudies............................................................. 475
8. Conclusionandfutureprospectus .................................................... 475
Authorcontributionandemailaddresses.................................................... 478
Conflictofinterests ............................................................. 478
Acknowledgements............................................................. 478
References................................................................. 478
1. Introduction
The World Health organization (WHO) estimated that 80% of the
population of developing countries relies on traditional medicines,
mostly herbal, medicines (Ekor, 2013). Some 40,000–70,000 plant spe-
cies have one or more medical applications in various systems of tradi-
tional medicines are inexpensive and readily available (Verpoorte,
2015). Around 60% of the global healthcare product market is domi-
nated by medicinally useful formulations and other health products, de-
rived or developed from plants (Mukherjee et al., 2010). According to
the World Health Organization, in 2008, world trade in herbal medicine
was estimated at US$83 billion which is continuously growing
(Robinson and Zhang, 2011; Booker et al., 2016). In recent years, inter-
est in the fields of secondary metabolites/natural products pertaining to
isolation, characterization, structure elucidation and bioactivity assess-
ment of the natural compounds have been tremendously increased.
The pharmaceutical sector focused attention on the development of
new innovative or indigenous plant-based drugs through investigation
of traditional systems of medicines (Patwardhan and Hooper, 1992;
Newman et al., 2003).
Swertia is one of the most diverse genera of herbs belonging to the
family Gentianaceae and comprising roughly 170 (Brahmachari et al.,
2004) or 135 (Kumar and Van Staden, 2016) species distributed
throughout the world, but are most diverse in temperate and subtropi-
cal regions and in montane tropics. In China, this genus is represented
by 79 species (Cao et al., 2013). In India, this genus is represented by
40 species,which mostly grow on mountainsmainly at the high altitude
(1200–3000 m) in the temperate Himalayan regions ranging from
Kashmir to Bhutan, and also in the Khasia and Western Ghats hills
(Chopra et al., 1956; Anonymous, 1982; and Scartezzini and Speroni,
2000)(Fig. 1).
Swertia spp. has been used globally in traditional medicines for
many years. In Bhutan, China, India, Japan, and Nepal, some Swertia
species are recognized for uses in traditional medicines to treat dif-
ferent diseases and ailments. Every underground and aerial parts of
Swertia species, including the leaf, stem, root, and seed are used in
the preparations of mixtures and decoctions to treat the various
ailments (Awan et al., 2013; Joshi, 2008; Joshi and Dhawan, 2005;
Kirtikar and Basu, 1984). Several books and modern texts have de-
scribed the botanical, phytochemical, ethnobotanical and pharmaco-
logical aspects of Swertia spp. (Khare, 2007; Kumar and Van Staden,
2016).
The genus Swertia exhibit a wide range of biological and pharmaco-
logical activities, including anticancer, anti-diabetic, antibacterial, anti-
oxidant, anti-hepatitis, anthelmintic, anti-leishmanial, neuroprotective.
In China, it has also been used as medicinal herbs for treating hepatitis,
cholecystitis, pneumonia, osteomyelitis, dysentery, and scabies (Cao
et al., 2013). However, traditionally, Swertia being used as a bitter tonic
in stimulating appetite and as a febrifuge in India whereas, in Japan
fortreating gastrointestinal diseases including nausea, gastroparesis,
and gastric atony.
Recently, the pharmacologically active phytochemicals from dif-
ferent Swertia spp. have been studied. Moreover, research has also
shown that Swertia plants yielded structurally diverse compounds in-
cluding xanthonoids, iridoids/secoiridoids, flavonoid, alkaloids, and
terpenoids (Pant et al., 2000). Recent pharmacological studies have
confirmed that the extracts or monomeric compounds of the genus
Swertia possess anticancer, antioxidant, anti-bacterial, hepatoprotec-
tive, and antidiabetic properties (cf. respective sections of this review
and references therein). These wide applications of Swertia spp. indi-
cate presence of several bioactive molecules in this plant enhances its
utility for extraction of drugs of diverse constituents for health
benefits.
Brahmachari et al. (2004) reviewed the chemical and pharmaco-
logical characteristics of Swertia spp. that were established before
2003. Recently, Kumar and Van Staden (2016) reviewed the ethno-
medical uses and biological activities of Swertia chirayita (Roxb. ex
Fleming) H. Karst. plant in traditional Indian medical systems.
These reviews strongly support further research on this genus. Con-
sidering their use in traditional medicine, Swertia spp. May be poten-
tially used to design drugs and healthcare products. Previously
research on this genus focused on its phytochemical characteristics,
whereas, earlier studies have focused on the pharmacological activity
and potential therapeutic applications of these plants. In the up to
445P.R. Kshirsagar et al. / South African Journal of Botany 124 (2019) 444–483
date years, significant advancements have been made on extensive
phytochemical investigations leading to elucidate the chemical and
pharmacological characteristics of the Swertia genus. Additionally,
in-depth studies have revealed the correlation among the
phytochemistry, pharmacological effects and traditional uses of
Swertia. New structurally diverse compounds have been successively
isolated from Swertia species (Brahmachari et al., 2004; Jamwal,
2012;Negi et al., 2011).
abc
de f
gh i
Swertia angustifolia var.
pulchella Swertia corymbosa Swertia densifolia
Swertia lawii Swertia minor Swertia angustifolia
Swertia bimaculata Swertia chirayita Swertia dilatata
j
Swertia nervosa
k
Swertia paniculata
Fig. 1. Morphology of Swertia species:a–e: Swertia species collected from Western Ghats of India; f–k: Swertia species collected from Himalayan region of India.
446 P.R. Kshirsagar et al. / South African Journal of Botany 124 (2019) 444–483
The present review is planned to give at present accessible data
on conventional and local information, issues involved in ethnobo-
tanical studies, a narrative of pharmacologically significant molecules,
and biochemical and pharmacological studies of this useful plant.
2. Methods
This review has been prepared based on a comprehensive survey of
literature conducted using major scientific databases such as Pubmed,
SciFinder, Google Scholar, Web of Science and a library search for arti-
cles published in peer-reviewed journals. In addition, information was
also acquired from available local books on Ethnopharmacology. Taxon-
omy was validated by referring the floras, books and online databases
Tropicos® (http://www.tropicos.org), The Plant List (http://www.
theplantlist.org), and The International Plant Name Index (http://
www.ipni.org) containing taxonomic information on plants. Similar
practice has been used to prepare tables. Keywords used for gathering
the references are Swertia, biological activity of Swertia,traditional
uses of Swertia, phytochemistry, pharmacology, antioxidant activity of
Swertia, antidiabetic, hepatoprotective, xanthones, terpenoids, seco-
Iridoid glycosides, oleanolic acid, antibacterial activity, geoghraphical
distribution and toxicity study. After gathering the references, results
were then analyzed individually and grouped together in a cohesive
presentation according to the theme of the review.
3. Ethnobotany
3.1. Taxonomy and general botanical aspects
The Gentianaceae family consists of 84 genera and about 970 species
in the world (Judd et al., 1999). Members of this family are widely dis-
tributed throughout the world but are most diverse in temperate and
subtropical regions and in montane tropics. The family Gentianaceae
is divided into three tribes: Exaceae, Chironeae, and Swertieae (Clarke,
1885). Cronquist (1988) treated the family under order Gentianales of
subclass Asteridae and class Magnoliopsida, while Judd et al. (1999)
considered it under order Gentianales and clade core asteroids. The
genus Swertia was founded by Linnaeus in 1753 in honor of Emanuele
Sweert (rarely spelled Swert, 1552–1612), a Flemish naturalist, one of
the precursors of the Dutch bulb-growing. The plant was first described
by Roxburgh under the name of Gentiana chyrayta in 1814. Swertia L. is
the most specious genus within the subtribe Swertiinae (Struwe et al.,
2002). Clarke (1885) divided Swertia into three subgenera: Ophelia,
Euswertia, and Poephila. About 170 known Swertia species are mainly
native to temperate regions of the northern hemisphere (Brahmachari
et al., 2004). About 40 species of Swertia are found in India, in the tem-
perate Himalayan region ranging from Kashmir to Bhutan, and also in
the Khasia and Western Ghats hills at high altitude (Chopra et al.,
1956; Anonymous, 1982 and Scartezzini and Speroni, 2000)(Fig. 1).
The botanical names, synonyms, common names, vernacular names
and geographical distribution of Swertia spp. are presented in Table 1
elaborating a wide adaptation of Swertia spp. under different ecological
surroundings. The process of evaluation in plants depended on the
changes in the environment and adapted to ample opportunities as
seen from the diversity in the Swertia species
3.2. History and traditional uses
Swertia species havebeen used in traditional Indian medical systems
(such as the Ayurveda, Unani and Siddha), traditional Chinese systems,
and traditional Tibetan folk medicines (Mukherji, 1953;Kirtikar and
Basu, 1984; Joshi and Dhawan, 2005; Geng et al., 2009a; Ping et al.,
2010). Most of the plants’organs/whole plants of Swertia species are
useful in local/indigenous medicine for the treatment of various ail-
ments (Table 2). Amongst all these species, Swertia chirayita (Roxb. ex
Fleming) H. Karst. is much esteemed by the Ayurvedic physician
because of its febrifuge, anthelmintic, tonic and laxative properties,
and is prescribed in case of malarial fever. The earliest recorded use is
in the Charaka Samhita Sutra (3rd–2nd century BCE), where the species
is recommended for reducing fever (jvaraghna) and purifying breast
milk (stanyasodhana) (Pradhan and Badola, 2015). Its medicinal usage
is reported in Indian pharmaceutical codex, the British and the
American pharmacopeias (Joshi and Dhawan, 2005). Swertia chirayita
(Roxb. ex Fleming) H. Karst. is also mentioned in the literature as
Swertia chirata, Buch.-Ham.; Ophelia chirata Grisebach.; Agathotes
chirayita Don.; Gentiana chirayita Roxburgh and Gentiana floribunda
Don. According to some previous resources, the species name Chirata
comes from the Sanskrit Kirata, the name of a mountain tribe of hunters
that live on high mountains, in wooden houses. A synonym of the plant
is Kirata tikta: tikta means “bitter,”“pungent,”“medicinal plant”which
becomes “the bitter plant of the Kiratas.”Kirata is also one of the names
of the God Shiva. In the Kiratarjuna, a part of the Mahabharata, the most
famous Indian epic poem, Shiva takes the appearance of a wild moun-
taineer called Kirata who fights with Arjuna, the mythical Indian hero
(Scartezzini and Speroni, 2000).
In India, Swertia chirayita (Roxb. ex Fleming) H. Karst is traditionally
being used as a bitter tonic in stimulating appetite, as a febrifuge, also
used against asthmaand liver disorders and it is reported to stop the in-
ternal hemorrhage of the stomach when taken with the sandalwood
paste (Ambasta, 1986). Swertia chirayita is used in British and
American pharmacopeias as tinctures and infusions. However according
to Ayurvedic pharmacology, chirata is described as bitter in the taste
(rasa) due to secoiridoid glycosides amarogentin (most bitter com-
pound isolated till date). The thermal action (virya) of chirata is defined
as cooling (shita). Chirata is light (laghu), i.e. easily digestible, and
ruksha (dry). A concoction of chirata with cardamom, turmeric and
kutki is given for gastrointestinal infections, and along with ginger is
considered good for the fever. To cure various skin problems it given
along with neem, manjishta and gotu kola. In cases of scorpion bite
treatment it is used in combination with other drugs (Joshi and
Dhawan, 2005). Seeds of S. chirayita are bitter, astringent, refrigerant,
diuretic, digestive, anthelmintic, ophthalmic, appetizer, tonic and
water purifier and leaves are used as a poultice, extract of the bark
and roots are used for the remedy of Cholera and Leprosy respectively
(Awan et al., 2013). The S. chirayita plants are dipped in water overnight
and the bitter juice is taken on next morning to cure malarial fever; de-
coction of the plant is used as tonic that influences the digestive organs
and also used as anthelmintic, especially for children; juice of the root is
taken to cure liver diseases; paste of the plant is also used in common
ailments like a cough, cold, asthma, headache, and fever; root paste
rubbed over joints for quick relief and leaves warmed and paste pre-
pared with mustard oil applied over boils and scabies (Joshi, 2008). Dif-
ferent concentrations of S. chirata extract also used in several herbal
formulations such as Ayush-64, Diabecon, Chirayita tablet, GlucoBuster,
DBCare, Himoliv, Mensturyl syrup, and Melicon V ointment as it offers
antipyretic, antifungal, antibacterial and hypoglycemic properties
(Edwin and Chungath, 1988; Mitra et al., 1996; Valecha et al., 2000;
Pradhan and Badola, 2015). It is one of the ingredients in Ayurvedic for-
mulations such as Kabdeen (for treating viral hepatitis), Sudarshan
churna, Mahasudarsana churna, Kiratatiktadai kvatha, Bhunimbadi
kvatha, Kiratadi taila (all for treating fever), Chandra Prabati (for can-
cer), Palas abijadi churna (anthelmintic), Dermafex oil (for skin prob-
lems), and as hair vitalizers (Pradhan and Badola, 2015). Some of the
common traditional and ethnomedicinal properties of Swertia spp.
have been summarized in Table 2.
Other medicinally important Swertia species are S. alata C.B. Clarke.
traditionally used as an appetite tonic and febrifuge (Chopra et al.,
1956), S. minor Knobl. used as a substitute for S. chirayita in the treat-
ment of malarial and other kinds of fever (Ambasta, 1986). Swertia
cordata (Wall. ex G. Don) C.B. Clarke and S. petiolata D. Don, both are
used for typhoid fever, pneumonia fever, throat problems and bronchi-
tis (Khan and Khatoon, 2008). Swertia angustifolia Buch.-Ham. ex D. Don
447P.R. Kshirsagar et al. / South African Journal of Botany 124 (2019) 444–483
Table 1
Common names, synonyms and geographical distribution of some Swertia species.
Sr.
no.
Name Synonyms Common Name Distribution
1Swertia binchuanensis T.N.
Ho& S.W. Liu (Accepted)
No synonyms bin chuan zhang ya
cai (Pinyin, China)
Yunnan, China
2Swertia davidii Franch.
(Accepted)
Swertia longipes. Franch. chuan dong zhang
ya cai (Pinyin,
China)
Hubei, Hunan, Sichuan, Yunnan province China
3Swertia erythrosticta Maxim.
(Accepted)
Swertia erythrosticta var. erythrosticta hong zhi zhang ya
cai (Pinyin, China)
Gansu, Hebei, Hunan, Nei Mongol Zizhiqu, Qinghai,
Shanxi, Sichuan province China; South Korea
4Swertia franchetiana Harry
Sm. (Accepted)
No synonyms bao jing zhang ya
cai (Pinyin, China)
Gansu, Qinghai, Sichuan, Xizang Zizhiqu Province
China
5Swertia japonica Makino.
(Unresolved)
Frasera japonica (Schult.) Toyok.; Gentiana japonica Schult.
(IR)
Sen-buri in
Japanese
Japan
6Swertia mussotii Franch.
(Accepted)
Swertia mussotii var. mussotii Di-da”and “Zang
Yin Chen”in China
high alpine lands of the Tibetan Plateau at altitudes
ranging between 3200 and 3800 m, tropical and
subtropical regions of the Asia, including India, Nepal
7Swertia pseudochinensis H.
Hara. (Accepted)
Ophelia pseudochinensis (H. Hara) Czerep. Frasera
pseudochinensis (H.Hara) Toyok. (IR)
liu mao zhang ya
cai (Pinyin, China)
Hebei, Nei Mongol Zizhiqu, Ningxia Hui, Shaanxi,
Shandong, Shanxi province China; Japan, South Korea
8Swertia pubescens Franch.
(Accepeted)
No synonyms mao zhang ya cai
(Pinyin, China)
Yunnan, China
9Swertia perennis L.
(Accepted)
Swertia punctata Baumg.; Blepharaden perennis (L.) Dulac;
Gentiana palustris All.; Gentiana paniculata Lam.; Swertia
alpestris Baumg.; Swertia manshurica (Kom.) Kitag.; Swertia
obtusa Ledeb.; Swertia perennis var. manshurica Kom.; Swertia
perennis var. obtusa (Ledeb.) Griseb.; Swertia perennis subsp.
obtusa Hara
Western North America, Switzerland
10 Swertia punicea Hemsl.
(Accepted)
Swertia punicea var. punicea “Ganyancao”and
"zi hong zhang ya
cai" (Pinyin, China)
Guizhou, Hubei, Hunan, Sichuan, Yunnan province
China
11 Swertia speciosa Wall.
(Accepted)
No synonyms Western Himalayas (Kashmir to Kumaon) India
12 Swertia alata C.B. Clarke.
(Accepted)
Ophelia alata (D. Don) Griseb. Pakistan, Kashmir (India), Nepal.
13 Swertia angustifolia
Buch.-Ham. ex D. Don
(Accepted)
Swertia angustifolia var. hamiltoniana Burkill; Swertia
angustifolia var. angustifolia
xia ye zhang ya cai
(Pinyin, China)
Pakistan, India, Nepal, Burma, Thailand, China,
Bhutan, Vietnam
14 Swertia bifolia Batalin.
(Accepted)
Swertia heterantha Ling er ye zhang ya cai
(Pinyin, China)
Gansu, Qinghai, Shaanxi, Sichuan, Xizang Zizhiqu
Province China
15 Swertia bimaculata (Siebold
& Zucc.) Hook. f. & Thomson
ex C.B. Clarke (Accepted)
Ophelia bimaculata Siebold & Zucc.; Silene esquirolii H. Lév.;
Swertia bimaculata var. macrocarpa Nakai; Swertia platyphylla
Merr.
zhang ya cai
(Pinyin, China)
Bhutan, Burma, China, India, Japan, Nepal, Vietnam
16 Swertia calycina Franch.
(Accepted)
No synonyms ye e zhang ya cai
(Pinyin, China)
Sichuan, Yunnan Province China
17 Swertia chirata Buch.-Ham.
ex Wall. (Unresolved)
Agathotes chirayta D.Don; Ericoila chirayta Bercht. & J.Presl;
Eyrythalia floribunda G.Don; Ophelia chirata Griseb. (IR)
Chirata (India) Temperate Himalayas (Kashmir to Bhutan) and
Khasia Hills (Meghalaya)
18 Swertia chirayita (Roxb.)
Buch.-Ham.ex C.B.Clarke
(Unresolved)
Gentiana chirayita Roxb. ex Fleming (IR) Sikkim Himalaya region, India
19 Swertia ciliata (D.Don ex G.
Don)B.L.Burtt (Accepted)
Ophelia ciliata D. Don ex G. Don; Ophelia dalhousiana Griseb.;
Ophelia purpurascens Wall. ex D. Don; Ophelia purpurascens
var. ciliata D. Don; Swertia purpurascens Boiss.
pu lan zhang ya cai
(Pinyin, China)
Afganistan, China (Xizang Zizhiqu), India, Nepal
20 Swertia cordata (Wall. ex G.
Don) C.B. Clarke (Accepted)
Ophelia cordata Wall. ex G. Don; Ophelia cordata var. laxa
Griseb.
xin ye zhang ya cai
(Pinyin, China)
Bhutan, Burma, China (Xizang Zizhiqu,Yunnan),
India, Nepal
21 Swertia corymbosa (Griseb.)
Wight ex. C.B. Clarke.
(Unresolved)
“Shirattakuchi”and
Siriaanangai or
“Poovainagai
(India)
Vellingiri hills Coimbatore, India
22 Swertia decora Franch.
(Accepted Name)
No synonyms guan shang zhang
ya cai (Pinyin,
China)
China (Sichuan, Yunnan)
23 Swertia decussata Nimmo ex
C.B.Clarke (Unresolved)
Ophelia alba Wight & Arn.; Ophelia densifolia Griseb.; Ophelia
multiflora Dalzell; Swertia densifolia (Griseb.) Kashyapa (IR)
India
24 Swertia delavayi Franch.
(Accepted)
No synonyms li jiang zhang ya cai
(Pinyin, China)
China (Sichuan, Yunnan)
25 Swertia densifolia (Griseb.)
Kashyapa (Unresolved)
Swertia decussata Nimmo ex C.B.Clarke (IR) India
26 Swertia hookeri C.B. Clarke
(Accepted)
No synonyms cu zhuang zhang ya
cai (Pinyin, China)
Bhutan, China (Xizang Zizhiqu), Nepal
27 Swertia lawii Burkill
(Unresolved)
No synonyms
28 Swertia longifolia Boiss.
*IUCN
Swertia aucheri Boiss.; Swertia persica Griseb. “Maryam Koohi”in
Persian.
Iraq, Iran and Turkey
29 Swertia macrosperma (C.B.
Clarke) C.B. Clarke
(Accepted)
Ophelia macrosperma C.B. Clarke; Swertia randaiensis Hayata da zi zhang ya cai
(Pinyin, China)
Bhutan, Burma, China (Guangxi, Guizhou, Hubei,
Sichuan, Taiwan, Yunnan), India, Nepal
448 P.R. Kshirsagar et al. / South African Journal of Botany 124 (2019) 444–483
plant is crushed and boiled in water and two teaspoonful decoction is
given 2–3 times a day to treat malaria fever and root juice and decoction
is used to give relief from cold and cough, to treat fever, blood purifier
and in bile disease (Joshi, 2008 and Malla and Chhetri, 2009). Swertia
cordata decoction is taken orally to cure gastric trouble and plant pow-
der is taken with warm water twice a day to cure fever (Singh, 2012)
and the whole plant is used in a treatment of disorders of the gall blad-
der (Sharma et al., 2011). Swertia trichotoma Wall. leaf extract serves as
a remedy for wormicidal use in animals (Rajan et al., 2005). Swertia
corymbosa (Griseb.) Wight ex. C.B. Clarke. have been used by Irulars
and Paliyan ethnic medical practitioners for the treatment of diarrhea,
fever, jaundice, diabetic, inflammation, anxiety, promote sleep, antiepi-
leptic, nervous disorders, antidote and as a stomach wash in cattle
(Abraham, 1981 and Brahmachari et al., 2004). Root juice of S. densifolia
(Griseb.) Kashyapa is taken once a day during leprosy (Kamble et al.,
2010).
A decoction of S. ciliate (D.Don ex G.Don) B.L.Burtt is given three
times a day for 5–7 days to control a cough, cold and fever. It is also
used as a substitute for S. chirayita (Joshi, 2008), the whole plant is
used as a tonic and febrifuge by the local inhabitants (Awan et al.,
2011). A paste of S. deltata var pilosa is applied locally to get relief
from joint pains; extract is used to treat scabies; juice of the plant is
taken orally twice a day before the meal to treat fever and headache. A
decoction of S. nervosa (Wall. Ex g. Don) C.B. Clarke root is applied in
skin diseases; plant is crushed and boiled in water and two teaspoonful
decoction is given twice a day in empty stomach to treat malaria fever;
extract of the plant is also given in the morning to cure “Gano”(Gasball)
and stomach problem. The decoction of S. paniculata Wall. is used as a
tonic and plant is used as a substitute for S. chirayita in a treatment of
malarial and other fever. The paste of S. pedicellata Banerji is applied
on the forehead to get relief from a headache. Two teaspoonful decoc-
tion of S. racemosa (Wall. ex Griseb.) C.B. Clarke is given twice a day to
treat fever and cough; paste of this plant is applied locally to treat ec-
zema and pimples; juice of aerial part is taken orally twice a day before
meals to treat jaundice. A decoction of S. ciliata (D.Don ex G.Don) B.L.
Burtt is given three times a day for 5–7 days to control a cough, cold
and fever (Joshi, 2008). The Paste of S. multicaulis D. Don applied over
wounds for healing; two to three teaspoonful of decoction of plant is
given twice a day to cure fever, cough and cold; decoction of plant is
also given for 2–3 days as anthelmintic (Joshi, 2008), this plant is also
used to cure fever, headache, and toothache (Yadav et al., 2010).
Different species of Swertia such as S. corymbosa, S. hookeri C.B.
Clarke, S. macrosperma (C.B. Clarke) C.B. Clarke,S.lawiiBurkill,S.
punctata Baumg., S. calycina Franch., S. petiolata,S. purpurascens Boiss.,
S. bimaculata (Siebold & Zucc.) Hook. f. & Thomson ex C.B. Clarke,S.ja-
ponica Makino.,and S. frachetiana Harry Sm. belong to the traditional
folk medicine and are being used as substitutes for S.chirayita in India,
China, Pakistan, Japan and other Asian countries in the treatment of
liver disorders, fevers, dysentery, diarrhea, stomach problems and
other ailments (Brahmachari et al., 2004). In China, 30 different Swertia
species have been used for medicinal purpose for treating hepatitis, cho-
lecystitis, pneumonia, osteomyelitis, dysentery, and scabies (Geng and
Chen, 2018). The range of bioactive molecules present in Swertia spp.
is vast as evident from the uses of Swertia in numerous health problems.
This possibly could be due to the plant’s exposures related to biotic and
abiotic stresses as well as developmental and metabolic plasticity. Uses
of different Swertia species categorised in different categories and sub-
categories and tabulated in table 3.
Table 1 (continued)
Sr.
no.
Name Synonyms Common Name Distribution
30 Swertia leduci Franch.
(Accepted)
Swertia mileensis T.N. Ho & W.L. Shih (IR) Mengzi
Zhangyacai;
“Qing-Ye-Dan”
Mengzi County of the Yunnan Province China
31 Swertia multicaulis D. Don
(Accepted)
Swertia multicaulis var. multicaulis duo jing zhang ya
cai (Pinyin, China)
Bhutan, China (Xizang Zizhiqu), Nepal
32 Swertia mussotii Franch.
(Accepted)
Swertia mussotii var. mussotii “ZangYinChen”high altitudes (2,000 to 5,000 metres above sea level)
in the Qinghai-Tibetan Plateau area in China
33 Swertia nervosa (Wall. ex G.
Don) C.B. Clarke (Accepted)
Agathotes nervosa Wall. ex G. Don, Swertia cavaleriei H. Lév. ye mai zhang ya cai
(Pinyin, China)
Bhutan, China (Gansu, Guangxi, Guizhou, Shaanxi,
Sichuan, Xizang Zizhiqu, Yunnan), India, Nepal
34 Swertia paniculata Wall.
(Accepted)
Ophelia paniculata D. Don; Ophelia paniculata var.
brachypetala Griseb.; Swertia dilatata C.B. Clarke; Swertia
stricta Collett & Hemsl.
kuan si zhang ya cai
(Pinyin, China)
Bhutan, Burma, china (Xizang Zizhiqu, Yunnan), India
(Kashmir, Mizoram), Nepal
35 Swertia pedicellata Banerji
(Unresolved)
Chiraito Nepal
36 Swertia petiolata D. Don
(Accepted)
No synonyms Afghanistan, Pakistan, India (Kashmir), Nepal, China.
37 Swertia przewalskii Pissjauk.
(Accepted)
No synonyms qi lian zhang ya cai
(Pinyin, China)
China (Qinghai)
38 Swertia quartiniana Hochst.
ex A. Rich. (Accepted)
No synonyms
39 Swertia racemosa (Wall. ex
Griseb.) C.B. Clarke
(Accepted)
Kingdon-wardia codonopsidoides C. Marquand;
Kingdon-wardia racemosa (Wall. ex Griseb.) T.N. Ho; Ophelia
racemosa Wall. ex Griseb.
zang zhang ya cai
(Pinyin, China)
Bhutan, China (Xizang Zizhiqu), India, Nepal
40 Swertia speciosa Wall.
(Accepted)
No synonyms Pakistan
41 Swertia trichotoma Wall.
(Unresolved)
Ophelia trichotoma Wight & Arn. (IR) India
42 Swertia yunnanensis Burkill.
(Accepted)
No synonyms
43 Swertia kouitchensis Franch.
(Accepted)
Swertia elongata T.N. Ho & S.W. Liu “Guizhou
Zhangyacai”,
“Shuihuanglian”or
“Silengcao”
Yunnan, Sichuan, Shaanxi, Hubei, Guizhou, Gansu
province, China
References: Tropicos® (http://www.tropicos.org), The Plant List (http://www.theplantlist.org), and The International Plant Name Index (http://www.ipni.org).
449P.R. Kshirsagar et al. / South African Journal of Botany 124 (2019) 444–483
Table 2
Some of the most important traditional and ethnomedicinal properties of some Swertia species.
Sr.
no.
Name Medicament Indications Route of
Administartion
References
1Swertia japonica
Makino.
Dry plant
decoction
Stomachia, antilaxantia, perfrictia, to treat gastrointestinal diseases including
nausea, gastroparesis, and gastric atony in Japan
El-Sedawy et al. (1989),
Kimura and Sumiyoshi
(2011)
2Swertia mussotii
Franch.
Gall and liver disorders Yang et al. (2005)
3Swertia alata C.B.
Clarke.
Whole plant Infusion of plants used as tonic and febrifuge Bhatt et al. (2007)
4Swertia angustifolia
Buch.-Ham. ex D. Don
Plant aueous
decoction
Malaria fever Joshi (2008),Malla and
Chhetri (2009)
Root juice and
decoction
Cold and cough, to treat fever, blood purifier and in bile disease Joshi (2008),Malla and
Chhetri (2009)
5Swertia chirata
Buch.-Ham.ex Wall.
Whole plant Stomachic, febrifuge and anthelmintic, anti-periodic, cathartic, asthma,
leucorrhoea, analeptic, stomachic, mitigate inflammation, relaxing to pregnant
uterus and never ending fevers
Joshi and Dhawan
(2005),Kirtikar and
Basu (1984)
6Swertia chirayita
(Roxb.) Buch.-Ham.ex
C.B.Clarke
Seeds Stimulates appetite, Asthma, liver disorders, anthelmintic, ophthalmic Awan et al. (2013)
Leaves Paultice Awan et al. (2013)
Root Cholera Awan et al. (2013)
Bark Leprosy Awan et al. (2013)
Overnight aqueous
extract of plant
To cure malarial fever Joshi (2008)
Decoction of the
plant
Anthelmintic Joshi (2008)
Root Juice Liver diseases Joshi (2008)
Plant paste Cough, cold, asthema, headache and fever Joshi (2008)
Root paste Joint pain Joshi (2008)
Warmed leaves
and paste with
mustard oil
Boils and scabies Joshi (2008)
7Swertia ciliata (D.Don
ex G.Don)B.L.Burtt
Decoction of the
plant
Cough, cold, and fever Joshi (2008)
8Swertia cordata (Wall.
ex G. Don) C.B. Clarke
Plant decoction Gastric trouble Oral Singh (2012)
Plant powder with
Warm water
Fever Singh (2012)
Whole plant Gall bladder disorders Sharma et al. (2011)
Unspecified Alterative, febrifuge, and anthelmintic Atta-ur-Rahman et al.
(1994)
9Swertia corymbosa
(Griseb.) Wight ex.
C.B. Clarke.
Unspecified Diarrhea, fever, jaundice, diabetes, inflammation, anxiety, promote sleep,
antiepileptic, nervous disorders, antidote
Abraham (1981),
Brahmachari et al.
(2004)
10 Swertia davidi Franch. Acute bacillary dysentery Kar et al. (2007),Rawat
et al. (2011)
11 Swertia deltata var.
pilosa
Whole plant paste Joint pains Applied
externally
Joshi (2008)
Whole plant
extract
Scabies Joshi (2008)
Whole plant Juice Fever and headache Oral Joshi (2008)
12 Swertia densifolia
(Griseb.) Kashyapa.
Root Juice Leprosy Kamble et al. (2010)
13 Swertia franchetiana
Harry Sm.
Hepatic, choleric, and inflammatory diseases, treatment of hepatogenous
jaundice and cholecystitis
Wang et al. (1994)
14 Swertia hookeri C.B.
Clarke
Whole plant Treatment of microbial infections in man, in hypertension and as a mood
enhancer
Ghosal et al. (1980)
15 Swertia japonica
Makino.
Gastrointestinal diseases including nausea, gastroparesis, and gastric atony Kimura and Sumiyoshi
(2011)
16 Swertia macrosperma
(C.B. Clarke) C.B.
Clarke
Whole plant Hepatitis, pyretic, antidote and diabetes Jia and Xiong (2017)
17 Swertia minor
(Griseb.) knobl.
Malaria and othe fever Kar et al. (2007),Rawat
et al. (2011)
18 Swertia multicaulis D.
Don
Whole plant paste Wounds Applied
externally
Joshi (2008)
Whole plant
Decoction
Fever, cough, cold and anthelmintic Joshi (2008)
unspecified Headache and toothache Yadav et al. (2010)
19 Swertia mussotii
Franch.
Hepatitis, diabetes, hyperlipidaemic effects. Liu et al. (2017)
20 Swertia nervosa (Wall.
Ex g. Don) C.B. Clarke
Root decoction Skin diseases Joshi (2008)
Whole plant
decoction
Malaria fever, Stomach problems Joshi (2008)
21 Swertia paniculata
Wall.
Decoction of the
plant
Malaria and othe fever Joshi (2008)
Certain mental disorders, such as melancholia Chopra et al. (1956)
22 Swertia pedicellata Whole plant paste Headache Joshi (2008)
450 P.R. Kshirsagar et al. / South African Journal of Botany 124 (2019) 444–483
4. Phytochemistry
The detailed and extensive phytochemical investigations on a num-
ber of Swertia species was led to an identification of an array of com-
pounds with varying structural patterns summarized in Tables 4–7.A
substantial number of these compounds are xanthonoids, iridoids/
secoiridoids, flavonoid, alkaloidsand terpenoids were isolated from sev-
eral Swertia spp. (Brahmachari et al., 2004; Jamwal, 2012). Some of
them have shown several bioactivities in vivo or in vitro,andsome
others have been increasingly studied in the fields of chemistry and bi-
ology for their broad spectrum of biological activities and novel struc-
tures (Table 9). Against this background, major benefits emerging
from modern chemistry technologies will assist to extract useful drugs
from several Swertia species. (See Table 8.)
The traditionally used Swertia species are rich sources of
Xanthonoids. Xanthonoids, i.e. 9H-xanthen-9-ones, constitute the
most abundant class of compounds present in Swertia. The xanthene
nucleus may be di-, tri-, tetra-, penta-, or polyoxygenated including gly-
cosidic linkages. Currently, more than 50 xanthonoids have been iso-
lated from Swertia species (Table 4).
There are approximately 40 terpenoids with basic steroidal frame-
works have been isolated from different Swertia species (Table 5). Fur-
thermore, oleanolic acid and ursolic acid were reported from different
Swertia spp. (Yang et al., 2004; Yang et al., 2005; Li et al., 2011; Gupta
et al., 2011). The presence of oleanolic acid in Swertia species and its dif-
ferent parts was studied by different authors (Table 7).
Phytochemical studies of genera Swertia demonstrated that these
species are rich sources of iridoids/iridoid glycosides such as
swertiamarin, amarogentin, amaroswerin and gentiopicroside com-
monly served as chemotaxonomic markers and characteristic com-
pounds within Swertia species (Pan et al., 2002). The secoiridoid
glycosides possess strong bitter principles especially common in theor-
ders Cornales, Dipsacales and Gentianales, are present in many herbal
preparations which are used for the treatment of stomach ailments
(Ghisalberti, 1998). The list of secoiridoid glycosides isolated from dif-
ferent species of Swertia have been given in Table 6 and some of these
compounds identified in Swertia spp.are diverse biological activities in-
cluding anti-allergic, antimicrobial, enzyme inhibitory, anti-parasitic,
anti-carcinogenic and anti-inflammatory which are summarized in
Table 9. Undoubtedly, members of the genus Swertia acquire effective
pharmacological perspective and promising activities of extracts in the
framework of ethnomedicinal knowledge, especially in tropical dis-
eases. Pharmacological research linking traditional mode of preparation
and application and knowledge gained from such studies could also
augment the effectiveness of already existing ethnomedicinal uses
and, therefore, support the cultural value of Swertia species.
5. Biological activities
5.1. Antioxidant activity
Antioxidants have been of interest to pharmacologists, biochemists,
and other health professionals because they are supposed to reduce oxi-
dative damage and protect the cell against oxidative stress caused by ac-
tive free radicals (Zhu et al., 2004). The natural antioxidants in fruits,
vegetables, spices and herbal medicines gained increasing interest
among food scientists, nutrition specialists, and consumers, as they re-
duce the risk of chronic diseases and promote human health (Niki, 2010).
In this context, various Swertia spp. extracts were investigated for
their free radical scavenging activities (Table 10). The antioxidant
capacity can be determined through various in vitro and in vivo antiox-
idant assays such as 1,1-diphenyl-1-picrylhydrazyl or 2,2- diphenyl-1-
picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline- 6-
sulphonic acid) (ABTS), superoxide (O2
•−
), nitric oxide, hydroxyl radi-
cal scavenging activity, ferric reducing antioxidant power, metal ion
chelating activity, anti-lipid peroxidation, chemiluminescence methods
were utilized.
In recent studies, satisfactory IC
50
values were reported which were
lower than those of some natural or synthetic antioxidants. The xanthone
derivatives bellidifolin, norswertianin and desmethylbellidifolin isolated
from Swertia japonica Makino. showed higher antioxidative potential
than those of commercial synthetic antioxidant butylated hydroxytolu-
ene (BHT) and α-tocopherol (Ashida et al., 1994). Similarly, the xan-
thones, 1,7,8-trihydroxy-3-methoxyxanthone (Swertianine) isolated
from Swertia decussata Nimmo ex C.B.Clarke was found to scavenge the
stable DPPH radical with an IC
0.200
value of 6.7 ± 0.2 mM which was
Table 2 (continued)
Sr.
no.
Name Medicament Indications Route of
Administartion
References
Banerji
23 Swertia petiolata D.
Don
Whole plant Cooling potency, anti-inflammatory activity, antitumor, as febrifuge, and as a
liver tonic,
Bader (2014)
Laxative, antialarial Kulanthaivel and
Pelletier (1988)
24 Swertia punicea
Hemsl.
Fever, intoxification, jaundice, and cholecystitis. Du et al. (2010)
25 Swertia racemosa
(Wall. ex Griseb.) C.B.
Clarke
Whole plant
decoction
Fever and Cough Oral Joshi (2008)
Aerial plant part
juice
Jaundice Oral Joshi (2008)
Whole plant paste Eczema and Pimples Applied locally Joshi (2008)
26 Swertia speciosa Wall. Roots Used as substitute for S. chirata Bhatt et al. (2007)
27 Swertia thomsonii C.B.
Clarke.
Whole plant Decoction used in head ache and fever Bhatt et al. (2007)
28 Swertia trichotoma
Wall.
Leaf extract Wormicide (in animals) Rajan et al. (2005)
29 Swertia kouitchensis
Franch.
Jaundice hepatitis, diabetes, dysentery, pneumonia, tonsillitis and gynecological
inflammation in central-western China
Wan et al. (2013b)
Whole plant
extract
Diabetes and hepatitis Cai et al. (2004)
30 Swertia mileensis T.N.
Ho & W.L. Shih
Hepatitis Geng et al. (2009a)
treatment of dark urine, heat astringent pain (painful urination,prostatitis and
BPH)
Wu et al. (2017b)
451P.R. Kshirsagar et al. / South African Journal of Botany 124 (2019) 444–483
extraordinary to that of the well-known antioxidant α-tocopherol show-
ing IC
0.200
value of 11.2 ± 0.1 mM. Additionally, Swertianine (100 μM)
which also showed strong protection against γ-radiation (dose
570 Gy/h for 2.45 min) induced DNA damage in pBR322 (Patro et al.,
2005). The unique structure of xanthones, including the unusual
catecholic moiety and completely conjugated system, enable them to
be the promising antioxidants molecules (Singh et al., 2012).
From the documented studies (Table 10), Swertia spp. showed mod-
erate to good antioxidant activity against the different free radicals.
However, more studies need to be conducted on antioxidant activity-
guided isolation and purification process in order to identify active com-
ponents in Swertia spp. crude extracts.
5.2. Antibacterial activity
The antibacterial activities of the several extracts and phytochemi-
cals from different parts of the Swertia species against different patho-
genic strains are shown in Table 11. The antibacterial activities are
frequently evaluated by using inhibition zone diameter (IZD) and
minimum inhibitory concentration (MIC) approaches. The xanthone,
1,2-dihydroxy-6-methoxyxanthone-8-O-β-D-xylopyranosyl
isolated from Swertia corymbosa (Grieb.) Wight ex C.B. Clark displayed
strongest antibacterial activity against Streptococcus pneumoniae and
Escherichia coli with MIC value of 3.90 μg/mL (Standard Ciprofloxacin
3.90 μg/mL) and 21.21 ± 0.25 (Ciprofloxacin 21.07 ± 0.05) and 20.27
± 0.11 (Ciprofloxacin 21.77 ± 0.11) mm zone of inhibition at 25
μg/mL concentration respectively (Mahendran et al., 2015). It is neces-
sary to purify antibacterial compounds extracted from Swertia, charac-
terized for targeting specific set of harmful bacteria. This will be more
precise for demonstrating the antibacterial activity of Swertia.
5.3. Anthelmintic activity
The effect of the crude aqueous and methanolic extracts of S. chirata
whole plant showed an anthelmintic effect on live Haemonchus
contortus. However, in the in vivo study, whole plant crude powder of
S. chirata administered crude aqueous and methanolic extracts at the
dose of 3 g/kg to sheep naturally infected with mixed species of gastro-
intestinal nematodes. A single oral dose of 7.5 mg/kg levamisole HCl
used as a positive control.
In vitro results indicated the crude methanolic extract (25 mg/ml) of
S. chirata whole plant inhibited completely the mobility of isolated
worms. The same activity was observed with 0.55 mg/ml of levamisole.
The crude methanolic extract and crude powder of S. chirata reveled
58.8 and 58.2% reduction in egg count in sheep at 3 g/kg on day 5
post-treatment respectively. Crude aqueous extract was lower effective
which resulted in 34% decrease in egg count in sheep on day 14 post-
treatment. Compare to this, standard anthelmintic agent levamisole ex-
hibited 99.6% (P N0.05) reduction in egg count with 7.5 mg/kg. These
results demonstrated that S. chirata whole plant has moderate anthel-
mintic activity. The results were supported the utilization of S. chirata
by farmers, in the form of crude powder in “massaulas”(physic
drench/balls) in the ethnoveterinary system of Pakistan as an anthel-
mintic agent (Iqbal et al., 2006). This is another desirable activity of
Swertia which can be exploited further based on accurate scientific
data and analysis.
5.4. Antidiabetic activity
Traditionally, there has been a record of Swertia spp. in the treatment
of diabetes (Chhetri et al., 2005; Li et al., 2004). The antidiabetic activi-
ties of the several extracts and phytochemicals from different parts of
the Swertia species are shown in Table 12. The antidiabetic activities
are often evaluated in vitro and in vivo using different model systems.
A number of Swertia species such as S. chirayita (Chandrasekar et al.,
1990; Bajpai et al., 1991; Saxena et al., 1993; Renu et al., 2011; Alam
et al., 2011 and Verma et al., 2013), S. japonica (Basnet et al., 1994), S.
punicea Hemsl. (Tian et al., 2010); S. mussotii Franch. (Zheng et al.,
2014); S.bimaculata (Liu et al., 2013); S.corymbosa (Mahendran et al.,
2014), S.kouitchensis Franch. (Wan et al., 2013b), S.longifolia
(Saeidnia et al., 2016) were known to have anti-diabetic activity.
Numerous xanthones isolated from these genus, including
bellidifolin, mangiferin and methylswertianin, have been confirmed as
antidiabetic agents (Basnet et al., 1994;Muruganandan et al., 2005;
Tian et al., 2010). Zheng et al. (2014) showed that the 1,3,5,8-
tetrahydroxyxanthone isolated from the S.mussotii was the most active
α-glucosidase andaldose reductase (ALR2) inhibitor, with IC
50
values of
5.2 ± 0.3 μM and 88.6 ± 1.6 nM, respectively. Therefore,
1,3,5,8-tetrahydroxyxanthone is considered most promising multitar-
get antidiabetic agent.
Moreover, the antidiabetic activity of methylswertianin has been
well established in animal models (Tian et al., 2010). The ethyl acetate
fraction of S. punicea Helmsl. containing methylswertianin and
bellidifolin apparently reduced fasting blood glucose levels in
streptozotocin (STZ) induced type 2 diabetic male BABL/c mice, with
the optimal doses of 200 and 100 mg/kg b.w./day, respectively (Tian
et al., 2010). Later, Tian et al. (2010) investigated that methylswertianin
and bellidifolin significantly enhanced the oral glucose tolerance, how-
ever lowered fasting serum insulin (FINS). Moreover, the post-
administration evaluation revealed low-density lipoprotein cholesterol
(LDL), lower serum total cholesterol (TC) and triglyceride (TG) levels
with increased relative high-density lipoprotein cholesterol (HDL) con-
centrations (HDL/TC). Methylswertianin and bellidifolin resulted to im-
prove insulin resistance by enhancing insulin signaling, similarly
expression levels of insulin-receptor a subunit (InsR-a), insulin-
receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI3K)
were also increased. These result concluded that methylswertianin
and bellidifolin could be useful for treating type-2 diabetes, possibly
via improvement in insulin resistance (IR).
Liu et al. (2013) explored the anti-diabetic activities of S. bimaculata.
Based on the glucose consumption of S.bimaculata extracts and different
fractions (petroleum, dichloromethane, ethyl acetate, n-butanol and
water extracts) in 3T3-L1 adipocyte assay, ethanol (ETH) and dichloro-
methane (DTH) extracts had the most effective potency. ETH, DTH and
corymbiferin (the most abundant component of DTH) were evaluated
for anti-diabetic effects and oserved that DTH and corymbiferin displayed
remarkable anti-diabetic activities in high fat and sucrose fed combined
with low dose streptozocin induced diabetic rats. Whereas serum total
cholesterol, density lipoprotein (LDL) and triglyceride levels lowered
and increased ratio of HDL (high density lipoprotein)/LDL were observed.
Increased expressions of insulin-receptor substrate-2, phos-
phatidylinositol 3-kinase and Ser/Thr kinase AKT2The improved insulin
sensitivity. Antioxidant capacity and carbohydrate metabolism improved
by DTH and corymbiferin in diabetic rats, along with improvement of his-
topathology of livers and pancreatic βcells. Corymbiferin was one of the
active constituents, responsible for anti-diabetic properties hence S.
bimaculata could be considered as an alternative agent. Several herbal
products are in the market which is advised as anti-diabetic formulations
but many of these products do not base on clinical studies and also con-
tain anti nutritional factors. It is essential as far as Swertia is concerned
to conduct proper detail studies to use this plant as an antidiabetic source
basedonthereportslistedabove.
5.5. Anticonvulsant activity
Mahendran et al. (2014) explored anticonvulsant activity of the
Swertia corymbosa methanolic extract (SCMeOH) against convulsions
induced by pentylenetetrazole (60 mg/kg b.w., i.p), isoniazid
(250 mg/kg b.w., i.p), and maximal electroshock (60 Hz alternating cur-
rent of 150 mA for 2 s was delivered through the ear electrodes) in al-
bino Swiss mice and Wistar albino rats. The results showed that
SCMeOH at the dose of 250 and 500 mg/kg protected 50.0% and 100%
452 P.R. Kshirsagar et al. / South African Journal of Botany 124 (2019) 444–483
of the mice against pentylenetetrazole induced convulsions, similarly
delayed the duration of isoniazid induced seizures from 56.77 ±
0.19 s in control to 34.62 ± 1.55 s, and 20.99 ± 2.24 s respectively. It
causes significant (Pb0.01 and Pb0.001) dose-dependent increase in
latency of convulsion. Also, administration of SCMeOH
(125–500 mg/kg) showed a dose-dependent increase in the delay of
the onset time of seizures induced by maximal electroshock induced
convulsion and also decreased the duration of tonic hind limb exten-
sion. Besides, HPLC analysis revealed that gentiopicroside
(40.726 mg/g) and swertianin (29.598 mg/g) were major components
of SCMeOH.
5.6. Anxiolytic properties
The anxiolytic activity of the methanolic extract of Swertia
corymbosa (SCMeOH) was tested by Mahendran et al. (2014).This
study was conducted on the behavioral model of young male albino
Swiss mice and Wistar albino rats by an open field, elevated-plus-
maze assessment. Results of this study indicated that the extract has a
selective anxiolytic effect with significantly modifying the locomotor
activity.
Table 3
DescriptionofusesofdifferentSwertia speciesincategoriesandsubcategories.⁎
Use category Use subcategory Description Species used References
Animal food ––––
Construction ––––
Cultural uses ––––
Environmental
uses
–––
Human food Beverages elaboration of unfermented or
fermented drinks Food Edible, generally
with little preparation Food Additives
Ingredients used in the preparation and
processing of foods
–– –
Medicinal and
veterinary
Blood and cardio-vascular system Jaundice S. racemosa; S. franchetiana; S. punicea; S.
kouitchensis
Joshi (2008),Wang et al. (1994),Du et al.
(2010),Wan et al. (2013b)
Dental health Tooth pains, S. multicaulis Yadav et al. (2010)
Digestive System Gastric or intestinal,
liver disorders,
hepatitis
S. chirayita; S. cordata; S.japonica; S.
mussotii; S. franchetiana; Swertia
macrosperma; S. kouitchensis; S. mileensis
Ambasta (1986),Awan et al. (2013),Joshi
(2008),Singh (2012)El-Sedawy et al.
(1989),Liu et al. (2017),Kimura and
Sumiyoshi (2011),Yang et al. (2005),
Wang et al. (1994) Jia and Xiong (2017),
Wan et al. (2013b),Geng et al. (2009b)
Endocrine system Diabetes S. chirata;S. corymbosa; S. macrosperma;
S. mussotii; S. kouitchensis
Mitra et al. (1996),Abraham (1981),
Brahmachari et al. (2004),Jia and Xiong
(2017),Liu et al. (2017),Wan et al.
(2013b)
General ailments with unspecific symptoms Headache, fever S. chirayita; S. cordata; S. petiolata; S.
angustifolia; S. corymbosa; S. ciliate; S.
deltata var pilosa; S. nervosa; S.
paniculata; S. pedicellata; S. racemosa; S.
multicaulis; S. thomsonii
Pradhan and Badola (2015),Joshi (2008),
Khan and Khatoon (2008),Malla and
Chhetri (2009),Abraham (1981),
Brahmachari et al. (2004),Yadav et al.
(2010), Bhatt et al. (2007)
Infections and infestations Malaria,
antihelminthic, scabies
S. chirayita; S. minor; S. deltata var pilosa Ambasta (1986),Joshi (2008), Kar et al.
(2007), Rawat et al. (2011)
Muscular-skeletal system Rheumatism, joints S. chirayita; S. deltata Joshi (2008)
Nervous system and mental health Mental disorders,
nervous disorders;
melancholia
S. corymbosa; S. paniculata Abraham (1981),Brahmachari et al.
(2004),Chopra et al. (1956)
Poisoning Scorpion, antidote S. chirayita, S. macrosperma Joshi and Dhawan (2005),Jia and Xiong
(2017)
Pregnancy, birth and puerperium Relaxing to pregnant
uterus and never
ending fevers
S. chirata Joshi and Dhawan (2005),Kirtikar and
Basu (1984)
Reproductive system and reproductive
health
Dark urine, heat
astringent pain
(painful
urination,prostatitis
and BPH)
S. mileensis Wu et al. (2017)
Respiratory system Flu, cold, cough S. ciliate; S. multicaulis; Swertia
angustifolia
Joshi (2008)
Skin and subcutaneous tissue Boils, eczema and
pimples, wounds
Swertia chirayita; S. nervosa; S. racemosa;
S. multicaulis
Joshi and Dhawan (2005),Joshi (2008)
Urinary system Urinary infections,
cystitis
S. punicea Du et al. (2010)
Other Uses not classifiable
within the previous
subcategories cancer,
anaesthetic, cholera
and leprosy
S. chirayita; S. densifolia Awan et al. (2013),Pradhan and Badola
(2015),Kamble et al. (2010)
Other uses Miscellaneous Hypertension and as a
mood enhancer
Swertia hookeri Ghosal et al. (1980)
⁎Categories and subcategories mentioned in table are described by Macea et al. (2011)
453P.R. Kshirsagar et al. / South African Journal of Botany 124 (2019) 444–483
Table 4
List of Xanthones isolated from Swertia species.
Sr.
no.
Xanthone Species References
1 1,8-dihydroxy-3-(3 hydroxybutoxy)xanthone (daviditin B) S. davidi Franch. Tan et al. (2003)
2 1-hydroxy-3,5-dimethoxyxanthone S. bifolia Batalin. Ji (2005)
S. chirayita
(Roxb.)
Buch.-Ham.ex
C.B.Clarke
Shi et al. (2005)
31-O-[β-D-xylopyranosyl(1 6)-β-Dglucopyranosyl]- 3,5-dimethoxyxanthone S. franchetiana
Harry Sm.
Wang et al. (2004)
4 1-hydroxy-3,7-dimethoxyxanthone S.
pseudochinensis
H. Hara.
Li et al. (2005)
5 1,2,6,8-tetrahydroxyxanthone (norswertianin) S. ciliata (D.Don
ex G.Don)B.L.
Burtt
Rahman et al. (2000)
6 1,2,8-trihydroxy-6-methoxyxanthone (gentiakochianin or swertianin) S. decora Franch. Xiao et al. (2001a)
S. delavayi
Franch.
Xiao et al. (2007)
S. punicea
Hemsl.
Zhang et al. (2007d)
S. yunnanensisi
Burkill.
Zi et al. (2000)
7 1,6,8-trihydroxy-2-methoxyxanthone (isobellidifolin or swertianol) S. longifolia
Boiss.
Hajimehdipour et al. (2006)
8 2,8-dihydroxy-1,6-dimethoxyxanthone (gentiacauleine) S. franchetiana
Harry Sm.
Wang et al. (2003)
S. longifolia
Boiss.
Hajimehdipour et al. (2003)
S. speciosa Wall. Rana and Rawat (2005)
9 1,8-dihydroxy-2,6-dimethoxyxanthone (swertiaperennine) S. longifolia
Boiss.
Hajimehdipour et al. (2003)
10 2,6,8-trihydroxy-1-O-β-Dglucopyranosylxanthone S. punctata
Baumg.
Menkovic et al. (2002)
11 1,3,5,8-tetrahydroxy xanthones (desmethyl bellidifolin) S. davidi Franch. Xu et al. (2005),Zhang et al. (2007e)
S.
pseudochinensis
H. Hara.
Li et al. (2005)
S. pubescens
Franch.
Xu and Yang (2005)
12 1,3,5-trihydroxy-8-O-β- glucopyranosylxanthone (norswertianolin) S. chirata
Buch.-Ham.ex
Wall.
Cai et al. (2006)
S. davidi Franch. Zeng et al. (2004)
S. erythrosticta
Maxim.
Li et al. (2002)
S. pubescens
Franch.
Xu and Yang (2005)
13 1,5,8-trihydroxy-3-methoxyxanthone (bellidifolin) S. binchuanensis
T.N. Ho& S.W.
Liu
Wang et al. (2008)
S. chirayita
(Roxb.)
Buch.-Ham.ex
C.B.Clarke
Shi et al. (2005),Cai et al. (2006)
S. ciliata (D.Don
ex G.Don)B.L.
Burtt
Rahman et al. (2000)
S. corymbosa
(Griseb.) Wight
ex. C.B. Clarke.
Saraswathy and Ariyanathan (2011)
S. davidi Franch. Xu et al. (2005)
S. franchetiana
Harry Sm.
Wang et al. (2003),Li et al. (2007a)
S. japonica
Makino.
Wang et al. (2008)
S. macrosperma
(C.B. Clarke) C.B.
Clarke
Guan et al. (2007),Zhang et al. (2007b)
S. mussotii
Franch.
Yang et al. (2005)
S.
pseudochinensis
H. Hara.
Li et al. (2005),Wang et al. (2008)
S. pubescens
Franch.
Xu and Yang (2005)
454 P.R. Kshirsagar et al. / South African Journal of Botany 124 (2019) 444–483
Table 4 (continued)
Sr.
no.
Xanthone Species References
S. punctata
Baumg.
Menkovic et al. (2002)
S. punicea
Hemsl.
Wang et al. (2008),Zhang et al. (2007d)
S. speciosa Wall. Rana and Rawat (2005)
14 1,8-dihydroxy-3,5-dimethoxyxanthone (methylbellifolin or swerchirin) S. bifolia Franch. Ji (2005)
S. chirayita
(Roxb.)
Buch.-Ham.ex
C.B.Clarke
Shi et al. (2005)
S. longifolia
Boiss.
Hajimehdipour et al. (2003),Hajimehdipoor et al. (2006)
S. macrosperma
(C.B. Clarke) C.B.
Clarke
Guan et al. (2007)
S. mussotii
Franch.
Yang et al. (2005)
S.
pseudochinensis
H. Hara.
Li et al. (2005)
S. punctata
Baumg.
Menkovic et al. (2002)
S. speciosa Wall. Rana and Rawat (2005)
S. yunnanensis
Burkill.
Zi et al. (2000)
15 1,3,8-trihydroxy-5-O-β-Dglucopyranosyl xanthones S. davidi Franch. Zeng et al. (2004)
16 1,5-dihydroxy-8-O-β-Dglucopyranosyl-3-methoxyxanthone (swertianolin) S.
binchuangensis
T.N. Ho& S.W.
Liu
Wang et al. (2008)
S. chirata
Buch.-Ham.ex
Wall.
Cai et al. (2006),Chakravarty et al. (2001)
S. ciliata (D.Don
ex G.Don)B.L.
Burtt
Rahman et al. (2000)
S. davidi Franch. Xu et al. (2005)
S. erythrosticta
Maxim.
Li et al. (2002)
S. franchetiana
Harry Sm.
Wang et al. (2004),Li et al. (2007a),Li et al. (2008),Tian
et al. (2005a)
S. japonica
Makino.
Wang et al. (2008)
S.
pseudochinensis
H. Hara.
Wang et al. (2008),Li et al. (2005)
S. pubescens
Franch.
Xu and Yang (2005)
S. punctata
Baumg.
Wang et al. (2008),Menkovic et al. (2002)
S. punicea
Hemsl.
Wang et al. (2008),Zhang et al. (2007d),Zhang et al.
(2007c),Zhang et al. (2006)
17 1,4,5,8-tetrahydro-1,5-dihydroxy-8-O-β-D-glucopranosyl-3-methoxyxanthone
(tetrahydroswertianolin)
S.
pseudochinensis
H. Hara.
Li et al. (2005)
18 1,8-dihydroxy-5-O-β-Dglucopyranosyl-3-methoxyxanthone (isoswertianolin) S. pubescens
Franch.
Xu and Yang (2005)
S. davidi Franch. Zeng et al. (2004)
19 8-hydroxy-1-O-primeverosyl-3,5-dimethoxyxanthone S. longifolia
Boiss.
Hajimehdipour et al. (2006)
20 3,8-dihydroxy-1-O-primeverosyl-5-methoxyxanthone S. punctata
Baumg.
Menkovic et al. (2002)
21 1,5-dihydroxy-6-O-primeverosyl-3-methoxyxanthone S. longifolia
Boiss.
Hajimehdipour et al. (2006)
22 1,5-dihydroxy-4-O-[β-xylose(2 1)rhamnose]-7-methoxyxanthone (pseudonolin) S. binchuanensis
T.N. Ho& S.W.
Liu
Wang et al. (2008)
S. japonica
Makino.
Wang et al. (2008)
S.
pseudochinensis
H. Hara.
Li et al. (2005)
S. punicea
Hemsl.
Wang et al. (2008)
(continued on next page)
455P.R. Kshirsagar et al. / South African Journal of Botany 124 (2019) 444–483
Table 4 (continued)
Sr.
no.
Xanthone Species References
23 1,3,8-trihydroxy-7-methoxyxanthone (isoswertianin) S. punctata
Baumg.
Menkovic et al. (2002)
24 1,7,8-trihydroxy-3-methoxyxanthone (swertianine) S. alata C.B.
Clarke.
Karan et al. (2005)
S. decussate
Nimmo ex C.B.
Clarke.
Patro et al. (2005)
S. thomsonii C.B.
Clarke
Ahmad et al. (2002)
25 1,7-dihydroxy-3,8-dimethoxyxanthone (gentiacaulien) S. bifolia Franch. Ji (2005)
S. davidi Franch. Tan et al. (2003)
S. nervosa (Wall.
Ex g. Don) C.B.
Clarke
Bhatia et al. (2004)
S. przewalskii
Pissjauk.
Yang et al. (2003)
S. punicea
Hemsl.
Zhang et al. (2007d)
S. thomsonii C.B.
Clarke.
Ahmad et al. (2002)
26 1,8-dihydroxy-3,7-dimethoxyxanthone (methlyswertianin or swertiaperennin) S. alata C.B.
Clarke.
Karan et al. (2005)
S. bifolia Franch. Ji (2005)
S. davidi Franch. Tan et al. (2003)
S. decora Franch. Xiao et al. (2001a)
S. delavayi
Franch.
Xiao et al. (2007)
S. franchetiana
Harry Sm.
Wang et al. (2003)
S. macrosperma
(C.B. Clarke) C.B.
Clarke
Guan et al. (2007)
S. mussotii
Franch.
Yang et al. (2005)
S. nervosa (Wall.
Ex g. Don) C.B.
Clarke
Bhatia et al. (2004)
S. punctata
Baumg.
Menkovic et al. (2002)
S. punicea
Hemsl.
Ming et al. (2000)
27 1-hydroxy-3,7,8-trimethoxyxanthone (decussatin) S. alata C.B.
Clarke.
Karan et al. (2005)
S. bifolia Franch. Ji (2005)
S. decora Franch. Xiao et al. (2001a)
S. franchetiana
Harry Sm.
Wang et al. (2003)
S. macrosperma
(C.B. Clarke) C.B.
Clarke
Guan et al. (2007)
S. nervosa (Wall.
Ex g. Don) C.B.
Clarke
Bhatia et al. (2004)
S. punicea
Hemsl.
Ming et al. (2000)
28 1,8-dihydroxy-7-O-β-D-glucopyranosyl-3-methoxyxanthone S. ciliata (D.Don
ex G.Don)B.L.
Burtt
Rahman et al. (2000)
S. mussotii
Franch.
Ma et al. (2005)
29 8-hydroxy-1-O-primeverosyl-3,7-dimethoxyxanthone S. punicea
Hemsl.
Ming et al. (2000)
30 8-hydroxy-1-O-β-D-glucopyranosyl-3,7-dimethoxyxanthone S. przewalskii
Pissjauk.
Yang et al. (2003)
31 8-hydroxy-1-O-gentiobiosyl-3,7-dimethoxyxanthone S. punctata
Baumg.
Menkovic et al. (2002)
32 1-O-primeverosyl-3,7,8-trimethoxyxanthone S. punicea
Hemsl.
Ming et al. (2000)
33 1,8-dihydroxy-7-O-[α-L-rhamnopyranosyl-(12)-β-D-xylopyranosyl]-3-methoxyxanthone S. franchetiana
Harry Sm.
Li et al. (2007a)
34 7-hydroxy-1-O-[β-D-xylopyranosyl-(1 4)-β-D-xylopyranosyl]-3,8-dimethoxyxanthone S. thomsonii C.B.
Clarke.
Ahmad et al. (2002)
35 1-O-β-D-glucopyranosyl-3,7,8-trimethoxyxanthone S. franchetiana
Harry Sm.
Wang et al. (2004)
36 1,5-dihydroxy-2,3-dimethoxyxanthone S. mileensis T.N. Guo et al. (2003)
456 P.R. Kshirsagar et al. / South African Journal of Botany 124 (2019) 444–483