The genus Stephania - Dr. DS Kothari Postdoctoral Fellowship ...

Journal of Ethnopharmacology 132 (2010) 369–383 

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Journal of Ethnopharmacology 

journal homepage: www.elsevier.com/locate/jethpharm 

Review 

The genus Stephania (Menispermaceae): Chemical and pharmacological 

perspectives 

Deepak Kumar Semwal a,∗ , Ruchi Badoni b , Ravindra Semwal c , Sudhir Kumar Kothiyal b , 

Gur Jas Preet Singh a , Usha Rawat b 

a Department of Chemistry, Punjab University, Sector-14, Chandigarh 160014, Punjab, India 

b Department of Chemistry, University of Garhwal, Srinagar 246174, Uttarakhand, India 

c Faculty of Pharmacy, Dehradun Institute of Technology, Dehradun 248009, Uttarakhand, India 

article 

info 

abstract 

Article history: 

Received 13 June 2010 

Received in revised form 22 August 2010 

Accepted 22 August 2010 

Available online 27 August 2010 

Key words: 

Stephania species 

S. cepharantha 

S. glabra 

S. japonica 

S. venosa 

Berberines 

Antiproliferative 

Hyperglycemia 

The plants of the genus Stephania (Menispermaceae) are widely distributed, and have long been used 

in folk medicine for the treatment of various ailments such as asthma, tuberculosis, dysentery, hyperglycemia, 

malaria, cancer and fever. Over 150 alkaloids together with flavonoids, lignans, steroids, 

terpenoids and coumarins have been identified in the genus, and many of these have been evaluated 

for biological activity. This review presents comprehensive information on the chemistry and pharmacology 

of the genus together with the traditional uses of many of its plants. In addition, this review 

discusses the structure–activity relationship of different compounds as well as recent developments and 

the scope for future research in this aspect. 

© 2010 Elsevier Ireland Ltd. All rights reserved. 

Contents 

1. Introduction .......................................................................................................................................... 370 

2. Traditional uses ...................................................................................................................................... 370 

3. Chemical constituents ............................................................................................................................... 371 

3.1. Stephania abyssinica Walp. ................................................................................................................... 371 

3.2. Stephania aculeata F. M. Bailey ............................................................................................................... 371 

3.3. Stephania bancroftii F. M. Bailey .............................................................................................................. 371 

3.4. Stephania brachyandra Diels .................................................................................................................. 371 

3.5. Stephania cepharantha Hayata ................................................................................................................ 371 

3.6. Stephania dinklagei Diels ..................................................................................................................... 372 

3.7. Stephania delovayi Diels ...................................................................................................................... 372 

3.8. Stephania elegans Hook.f. & Thoms. .......................................................................................................... 372 

3.9. Stephania erecta Craib ........................................................................................................................ 373 

3.10. Stephania excentrica H.S.Lo................................................................................................................. 373 

3.11. Stephania glabra (Roxb.) Miers .............................................................................................................. 373 

3.12. Stephania hernandifolia (Willd.) Walp. ...................................................................................................... 373 

3.13. Stephania intermedia H.S.Lo................................................................................................................ 374 

3.14. Stephania japonica (Thunb.) Miers .......................................................................................................... 374 

3.15. Stephania longa Lour ........................................................................................................................ 374 

3.16. Stephania miyiensis S.Y.Zhao&H.S.Lo.................................................................................................... 374 

∗ Corresponding author. Tel.: +91 9412947995. 

E-mail address: dr dks.1983@yahoo.co.in (D.K. Semwal). 

0378-8741/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. 

doi:10.1016/j.jep.2010.08.047

370 D.K. Semwal et al. / Journal of Ethnopharmacology 132 (2010) 369–383 

3.17. Stephania pierrei Diels ....................................................................................................................... 375 

3.18. Stephania gracilenta Miers .................................................................................................................. 375 

3.19. Stephania rotunda Lour. ..................................................................................................................... 375 

3.20. Stephania sasakii Hayata .................................................................................................................... 375 

3.21. Stephania sinica Diels........................................................................................................................ 375 

3.22. Stephania suberosa L. L. Forman ............................................................................................................. 375 

3.23. Stephania succifera H. S. Lo & Y. Tsoong ..................................................................................................... 375 

3.24. Stephania sutchuenensis H.S.Lo............................................................................................................. 376 

3.25. Stephania tetrandra S. Moore ................................................................................................................ 376 

3.26. Stephania venosa (Blume) Spreng. .......................................................................................................... 376 

4. Biological activities................................................................................................................................... 376 

4.1. Anti-malarial activity ......................................................................................................................... 376 

4.2. Antimicrobial activity ........................................................................................................................ 376 

4.3. Anthelmintic activity ......................................................................................................................... 377 

4.4. Anti-viral activity ............................................................................................................................. 377 

4.5. Anti-proliferative/anti-cancer activity ....................................................................................................... 377 

4.6. Antipsychotic activity ........................................................................................................................ 377 

4.7. Apoptosis inducing effect .................................................................................................................... 377 

4.8. Multidrug resistance reversing activity ...................................................................................................... 377 

4.9. Anti-inflammatory and analgesic activity ................................................................................................... 378 

4.10. Immunomodulating activity ................................................................................................................ 378 

4.11. Antifibrotic effect ........................................................................................................................... 378 

4.12. Anti-hyperglycemic effect .................................................................................................................. 378 

4.13. Ca 2+ channel blocking activity .............................................................................................................. 378 

4.14. Acetylcholinesterase (AChE) inhibitory activity ............................................................................................ 379 

4.15. Vasodilating and hypotensive activities .................................................................................................... 379 

4.16. Inhibition of antinociceptive effect ......................................................................................................... 379 

4.17. Acute hemodynamic effect ................................................................................................................. 379 

4.18. Histamine release inhibition activity ....................................................................................................... 379 

4.19. Antioxidant activity ......................................................................................................................... 379 

4.20. Miscellaneous uses .......................................................................................................................... 379 

4.21. Toxic effects ................................................................................................................................. 380 

5. Future perspectives and conclusion ................................................................................................................. 380 

Acknowledgements .................................................................................................................................. 380 

References ........................................................................................................................................... 380 

1. Introduction 

The genus Stephania belongs to family Menispermaceae, a large 

family of about 65 genera and 350 species, distributed in warmer 

parts of the world. The members of this family are mostly herbs 

or shrubs but rarely trees. The plants of the genus Stephania are 

slender climbers with peltate and membranous leaves. The flowers 

are umbelliform cymes while inflorescence are axillary and arising 

from old leafless stem. These plants have recognized medicinal values 

and traditionally have been used for the treatment of asthma, 

tuberculosis, dysentery, hyperglycemia, cancer, fever, intestinal 

complaints, sleep disturbances and inflammation (Chopra et al., 

1958; Gaur, 1999; Kirtikar and Basu, 2004). 

Over the last five decades, an extensive amount of chemical 

work has been done on many of these plants because of their traditional 

uses which are of interest to researchers. These plants are 

major sources of bioactive alkaloids such as morphines, hasubanalactams, 

hasubanans, aporphines and berberines. The majority 

of the chemical work has been reported on S. tetrandra S. Moore, 

S. cepharantha Hayata, S. glabra (Roxb.) Miers, S. japonica (Thunb.) 

Miers and S. venosa (Blume) Spreng, and more than 70 alkaloids 

along with other minor constituents have been reported from these 

five species alone. Many of these plants are known for their distinct 

biological importance including antitumor and emetine type 

activity (Kuroda et al., 1976; Gupta et al., 1980). 

In past decade, Chinese-herb nephropathy, a progressive interstitial 

nephropathy has been observed among women in Belgium 

after the intake of weight-reducing pills containing S. tetrandra 

S. Moore. Phytochemical analyses of these pills resulted in the 

identification of aristolochic acids (responsible for nephropathy) 

instead of tetrandrine (responsible for weight reduction), confirming 

the replacement of S. tetrandra (han fangji) by Aristolochia 

fangchi (guang fangji/fangchi). These are different plants and the 

chemical composition also different. Similarity in the nomenclature 

of both these plants was only reason behind the substitution 

(Vanherweghem et al., 1993; Debelle et al., 2002; Mosihuzzaman 

and Choudhary, 2008). 

This study is an attempt to compile an up-to-date and comprehensive 

review of the genus Stephania that covers its traditional 

medicinal uses, chemistry and pharmacology. Many plants of this 

genus are pharmacologically known but chemically unknown and 

vice-versa. Therefore, the scope of future research in this aspect is 

also discussed here. 

2. Traditional uses 

In traditional medicine, most of the plants of the genus Stephania 

have been used to treat a wide variety of ailments such as dysentery, 

pyrexia, tuberculosis, diarrhea, dyspepsia, urinary diseases, 

abdominal ills, asthma, ascariasis, dysmenorrhea, indigestion, 

wounds, head-ache, sore-breasts and leprosy. The rhizome extract 

of S. glabra (Roxb.) Miers has long been used as antidysenteric, 

antipyretic, antiasthamatic and antituberculosis agent (Chopra et 

al., 1958; Kirtikar and Basu, 2004). The aqueous concoction of the 

powders of the dried rhizome of S. glabra (Roxb.) Miers and aerial 

root of Trichosanthes multiloba are used as an anthelmintic against 

intestinal worms in Meghalaya (Northeast India) (Das et al., 2004). 

S. venosa (Blume) Spreng is often used as a bitter tonic (Pharadai et 

al., 1985). The stems of S. dinklagei Diels possess vermifuge, aphrodisiac, 

analgesic and sedative effects whereas the leaves has been

D.K. Semwal et al. / Journal of Ethnopharmacology 132 (2010) 369–383 371 

used to treat infertility in the female and impotence in the male. The 

roots of S. hernandifolia (Willd.) Walp. were used in fever, diarrhea, 

dyspepsia and urinary diseases (Chopra et al., 1958). S. rotunda Lour. 

has been used to treat pulmonary consumption, dysentery, fever, 

abdominal ills (tubers), asthma (tubers and stems), ascariasis, dysmenorrhea 

(stems), indigestion, wounds, head-ache, sore-breasts 

(leaves) and leprosy (flowers) (Chopra et al., 1958; Burkill, 1966; 

Phaet-thanesuara, 1967; Khasiphand and Suksah, 1968; Perry, 

1980). The root of S. tetrandra S. Moore have been used in hepatofibrogenic 

disease (Chen et al., 2005), it also used as diuretic, 

antiphlogistic, antirheumatic (Joshi et al., 2008), antipyretic and 

analgesic in China for centuries (Achike and Kwan, 2002). S. cepharantha 

Hayata has been used to treat many acute and chronic diseases, 

including venomous snakebites in Japan (Kimoto et al., 1997). 

In Bangladesh, the vines of S. japonica (Thunb.) Miers were used for 

leucorrhoea, presence of semen in urine, burning sensations during 

urination by Chakma and Tonchonga tribes (Hossan et al., 2010). 

3.3. Stephania bancroftii F. M. Bailey 

(−)-Tetrahydropalmatine (5), (−)-stephanine (6), (−)-crebanine 

(7), ayuthianine (8), (+)-sebiferine and (+)-stepharine (9) 

(Blanchfield et al., 1993, 2003; Bartley et al., 1994). 

3. Chemical constituents 

The reported data showed that alkaloids are the main and 

common phytochemicals of the genus Stephania. More than 

200 alkaloids have been isolated from this genus together 

with flavonoids, lignans, steroids, terpenoids and coumarins. The 

reported phytochemicals from different plants of the genus are 

given as following. 

3.4. Stephania brachyandra Diels 

Sinoacutine, stephanine (6), crebanine (7) and (−)-dicentrine 

(10) (Shulin et al., 1992). 

3.1. Stephania abyssinica Walp. 

4 ′ -O-methylstephavanine (1) and stephavanine (2) (Dagne et 

al., 1993). 

3.5. Stephania cepharantha Hayata 

3.2. Stephania aculeata F. M. Bailey 

7-Hydroxyaporphine, (+)-laudanidine (3) and (−)-amurine (4) 

(Blanchfield et al., 1993, 2003). 

Stephaoxocanine, stephaoxocanidine, romorphinane, cepharanthine, 

cepharanoline, steponine, isotetrandrine, berbamine, 

stecepharine, dehydroreticuline (11), magnoflorine, menisperine, 

oblongine, cyclanoline, cis-N-methylcapaurine, sinomenine, 

cephamerphinanine, D-glucopyranoside, 2 ′ -N-methylisotetrandrine, 

N-methyl stesakine chloride (12), stesakine 9-O--Dglucoside 

(13), N-methylasimilobine-2-O--D-glucopyranoside 

(14), cephamonine, aromoline, zippelianine, cepharamine, aknadinine 

(15), aknadicine (16), cephatonine, (−)-cycleanine (28), 

obamegine, berbamine, isocorydine, anolobine, cotypalline, 

stepharine (9), (+)-reticuline (17), obaberine, homoaromoline, 

fangchinoline, tetrandrine (18), cephamuline (Deng et al., 1992; 

Nakamura et al., 1992; Sugimoto et al., 1993, 1988; Kashiwaba et 

al., 1996, 1997, 2000, 1998, 1994; Nakaoji et al., 1997; Tanahashi 

et al., 2000), berbamine and aromorine (Akasu et al., 1976).


3.6. Stephania dinklagei Diels 

Liriodenine (19), dicentrinone (20), (+)-corydine (21), (+)- 

idocorydine, (−)-roemerine, N-methylliriodendronine (22), 

2-O,N-dimethylliriodendronine (23), aloe-emodin (24), isocorydine, 

aporphines, atheroospermidine, tephalagine and 

dehydrostephalagine (Dwuma et al., 1980; Camacho et al., 

2000; Goren et al., 2003). 

3.7. Stephania delovayi Diels 

Stephodeline (Il’inskaya et al., 1973), 16-oxodelavayine 

(Il’inskaya et al., 1972), delavayine (25) (Fadeeva et al., 1971a) and 

isostephodeline (Perel’son et al., 1975). 

3.8. Stephania elegans Hook.f. & Thoms. 

Epihernandolinol (26), N-methylcorydalmine (27), hasubanonin, 

aknadinin (15), cyclanoline, magnoflorine, isotetrandrine, 

isochondodendrine and cycleanine (28) (Singh et al., 1981).


3.9. Stephania erecta Craib 

Cepharanthine, (+)-2-N-methyltelobine (29), (+)-1,2- 

dehydrotelobine (30), (+)-2-nor-isotetrandrine, (+)-isotetrandrine, 

(+)-2-nor-thalrugosine, (+)-thalrugosine, (+)-homoaromoline, 

(+)-stephibaberine, (+)-dephnandrine, (+)-2-nor-cepharanthine, 

(+)-nor-obaberine, (+)-obaberine (Likhitwitayawuid et al., 1993b; 

Tamez et al., 2005). 

3.11. Stephania glabra (Roxb.) Miers 

(+)-Pronuciferine (33), gindarine, gindaricine, gindarinine, 

hyndarine, magnoflorine, N-thyloxystephanine, 

N-methylhydoxystepharine, remerine, stephararine, cycleanine 

(28), rotundine, capaurine (34), corydalmine (35), stepholidine 

(36), stepharine (9), protoberberine, palmatine (37), dehydrocorydalmine 

(38), jatrorrhizine (39), stepharanine (40), columbamine 

(41), N-desmethycycleanine (42), corynoxidine (43) (Chaudhary 

and Siddiqui, 1950; Chaudhary et al., 1952; Chopra et al., 1956; 

Cava et al., 1964, 1968; Kin et al., 1965; Robinovich et al., 1965; 

Shchelchkova et al., 1965; Doskotch et al., 1967; Dhar et al., 

1968; Thu and Nuhn, 1971; Khanna et al., 1972; Patra et al., 

1980; Bhakuni and Gupta, 1982; Bhakuni, 1984; Mahatma et 

al., 1987; Anonymous, 1989; Rastogi and Mehrotra, 1991; Duke, 

1992; Das et al., 2004), 11-hydroxypalmatine (44) (Semwal et al., 

2010b), glabradine (45) and gindarudine (46) (Semwal and Rawat, 

2009a,b). 

3.10. Stephania excentrica H. S. Lo 

Excentricine (31), N-methylexcentricine (32), roemerine, 4- 

demethylhasubanonine, oxoputerine, oxoanolobine, isoboldine, 

homoaromoline, (+)-coclaurine and sinococuline (Deng and Zhao, 

1997; Miu et al., 1998). 

3.12. Stephania hernandifolia (Willd.) Walp. 

(+)-3 ′ ,4 ′ -Dihydrostephasubine (47), (+)-epistephanine (48), 

(+)-stephasubine (49) (Patra et al., 1988), l-quercitol, isotrilobine, 

-sitosterol, aknadine, aknadinine (15), 4-demethylhasubanonine, 

dl-tetrandrine, fangchinoline (50), d-tetrandrine (18), d- 

isochondrodendrine, aknadicine (16) (Chopra et al., 1956; Moza, 

1960; Kupchan et al., 1961; Kunitomo et al., 1966, 1967, 1969; 

Moza and Basu, 1966; Moza and Bose, 1967; Kupchan et al., 

1968; Moza et al., 1968; Moza et al., 1970; Anonymous, 1994), 

hernandoline (Fadeeva et al., 1967), hernandine (Il’inskaya et al., 

1971), hernandolinol (Fadeeva et al., 1970), methylhernandine 

(Fadeeva et al., 1971b), 3-O-demethylhernandifoline (51)(Fadeeva 

et al., 1972) and hernandifoline (Fesenko et al., 1971).


3.13. Stephania intermedia H. S. Lo 

(−)-Stepholidine (36) (Xin et al., 1992; Ellenbroek et al., 2006). 

3.14. Stephania japonica (Thunb.) Miers 

16-Oxohasubonine, aknadicine (16), aknadine, 16-oxoprotometaphanine, 

aknadinine (15), cyclanoline, cycleanine (28), 

d-fangchinoline (50), oxostephabenine (52), stephabenine 

(53), lanuginosine (54), epistephanine, dehydroepistephanine, 

d-tetrandrine (18), trilobine, epistephamiersine, insularine, 

hasubanonine, hernandoline, obamegine, homoepistephanine, 

steponine, stephasunoline, oxostephasunoline (55), homostephanoline, 

hypoepistephanine, isochondrodendrine, oxostephamiersine, 

isotrilobine, l-quercitol, metaphanine, n-nor-1, 

2-dehydroepistephanine, oxostephanine, plastoquinone, protostephanaberrine, 

prometaphanine, stepinonine, stebisimine, 

oxostephasunodine, stephanaberrine, stephanine (6), prostephanaberrine 

(56), stephamiersine, stephanoline, stepholine, 

stepisimine, viburnitol, protostephanine (57), oxoepistephamiersine 

(58), oxostephamiersine, stephadiamine (Inubushi and Ibuka, 

1977; Matsui and Watanabe, 1984; Matsui et al., 1984, 1973, 

1982a,b; Matsui et al., 1975; Kondo et al., 1983; Taga et al., 1984; 

Yamamura and Matsui, 1985; Matsui and Yamamura, 1986; Duke, 

1992; Hall and Chang, 1997) and bebeerine (59) (Hullatti and 

Sharada, 2010). 

3.15. Stephania longa Lour 

Longitherine (60), stephabyssine, stephaboline (Deng and Zhao, 

1993), isostephaboline, stephalonines A-I, norprostephabyssine 

(61), isoprostephabyssine (62), isoprostephabyssine and isolonganone 

(Zhang and Yue, 2005). 

3.16. Stephania miyiensis S. Y. Zhao & H. S. Lo 

Tetrahydropalmatine (5), stepharine (9), corydalmine (35), jatrorrhizine 

(39), stepharanine (40) and 4-O-demethyljatrorrhizine 

(63) (Anonymous, 1999).


3.20. Stephania sasakii Hayata 

Obaberine, thalrugosine, aknadinine (15), secocepharanthine, 

aknadilactam (70) and O-methylpunjabine (Moza et al., 1970; 

Kunitomo, 1985). 

3.17. Stephania pierrei Diels 

(−)-Asimilobine (64), (−)-asimilobine 2-O--D-glucoside, 

(−)-anonaine, (−)-isolaureline, (−)-xylopine, (−)-roemeroline, 

(−)-dicentrine (10), (−)-nordicentrine, (−)-phanostenine, 

cassythicine, magnoflorine, (−)-tetrahydropalmatine (5), 

(−)-capaurine (34), (−)-thaicanine, (−)-corydalmine (35), 

(−)-N-methyltetrahydropalmatine (65), (−)-xylopinine, 

(−)-tetrahydrostephabine, (+)-reticuline (17), (+)-codamine, (±)- 

oblongine, (−)-delavaine and (−)-salutaridine (Likhitwitayawuid 

et al., 1993a; Angerhofer et al., 1999). 

3.21. Stephania sinica Diels 

Cepharanthine (69), runanine (71) and -sitosterol (Min et al., 

1985). 

3.18. Stephania gracilenta Miers 

Sinoacutine, isosinoacutine (66), magnoflorine and papaverine 

(67) (Khosa et al., 1987). 

3.22. Stephania suberosa L. L. Forman 

3.19. Stephania rotunda Lour. 

Cepharamine (68), cycleanine (28), (+)-stepharine (9), (−)- 

tetrahydropalmatine (5)(Chopra et al., 1958; Burkill, 1966; Tomita 

et al., 1966; Tomita and Kozuka, 1966, 1967; Phaet-thanesuara, 

1967; Perry, 1980; Kozuka et al., 1985; Luger et al., 1998), coclaurine, 

dehassiline, stepholidine (36), corynoxidine (43) (Thuy et 

al., 2006), stepharotudine (Hung et al., 2010), cepharanthine (69), 

fangchinoline (50)(Gulcin et al., 2010), 5-hydroxy-6,7-dimethoxy- 

3,4-dihydroisoquinolin-1(2H)-one, thaicanine 4-O--D-glucoside 

and (−)-thaicanine N-oxide (4-hydroxycorynoxidine) (Thuy et al., 

2005). 

(+)-Cepharanthine (69), (+)-2-norcepharanthine (72), 

(+)-cepharanthine 2 ′ --N-oxide, (+)-stephasubine, (+)- 

norstephasubine, stephasubimine (73) (Patra et al., 1986), 

(−)-tetrahydrostephabine, (−)-kikemanine, (−)-stephabinamine, 

tephabine, stephnubine, (−)-discretine, 8-oxypseudopalmatine, 

(−)-tetrahydropalmatrubine, (−)-stepholidine (36), (−)- 

capaurimine, pseudopalmatine, (−)-coreximine, stephaphylline 

(−)-ctytenchine, (−)-xylopinine and nordelavaine (Patra et al., 

1987; Patra, 1987). 

3.23. Stephania succifera H. S. Lo & Y. Tsoong 

Cepharanone D, N-formyl-asimilobine, N-formyl-annonain 

(Yang et al., 2010a,b), crebanine (7), crebanine-N-oxide, dehydrocrebanine, 

tetrahydropalmatine (5), schefferine, asimilobine (Xue 

et al., 1986), 7-oxodehydrocaaverine, 7-oxocrebanine and aristololactam 

I (Yang et al., 2010a,b).


3.24. Stephania sutchuenensis H. S. Lo 

1-Nitroaknadinine (74) and aknadinine (15)(Wang et al., 1994). 

3.25. Stephania tetrandra S. Moore 

Stephadione (75), oxonantenine (76), cassameridine, nantenine, 

cassythicine, corydione, aristolochic acid I and II, fangchinoline 

A-D (Chen and Chen, 1935; Chen et al., 1937; Si et al., 1992; Zhu 

and Philipson, 1996; Kwan et al., 1996; Kim et al., 1997; Ogino et 

al., 1998b; Wong, 1998; Kim et al., 1999; Nan et al., 2000; Liang 

et al., 2002; Tsutsumi et al., 2003; Fang et al., 2005; Chiou et al., 

2006), fenfangjine A-C (Ogino et al., 1998a), stephaflavone A and 

B(Si et al., 2001), fangchinoline (50), tetrandrine (18) (Lijin et al., 

2009), 2-N-methyltetrandrine and (+)-2-N-merhylfangchinoline 

(77) (Deng et al., 1990). 

well as aqueous extract (SA) and dichloromethane extracts (SD1 

and SD2) from S. rotunda Lour. were tested against Plasmodium falciparum 

W2 in vitro. DN, CN and SD1 were the most active against W2 

with IC 50 values of 0.36, 0.61 M and 0.7 g/mL, respectively. Their 

IC 50 values on human monocytic THP1 cells were 10.8, 10.3 M 

and >250 g/mL, respectively. CN, SD1 and SA were selected for in 

vivo antimalarial testing against Plasmodium berghei in mice. The 

results of SD1 and SA at a dose of 150 mg/kg showed a decrease of 

89 and 74% of parasitaemia by intra-peritoneal injection and 62.5 

and 46.5% of parasitaemia by oral administration, respectively. The 

results for CN at a dose of 10 mg/kg showed a decrease of 47% of 

parasitaemia by intra-peritoneal injection and 50% of parasitaemia 

by oral administration. Drug interaction of chloroquine (CL) and 

major alkaloids indicates that CN–CL and TN–XN associations 

are synergistic (Chea et al., 2007). The bisbenzylisoquinoline 

alkaloids from S. erecta Craib and tetrahydroprotoberberine alkaloids 

from S. pierrei Diels showed anti-malarial activity against 

the D6 (ED, 1540 ng/mL) and W2 (ED, 3130 ng/mL) strains of 

Plasmodium falciparm having ED values of 950 and 470 ng/mL 

in the D6 and W2 strains, respectively. The antimalarial activity 

of S. pierrei Diels was attributed to the nonquaternary aporphine 

alkaloids and the tetrahydroprotoberberines possessing a 

phenolic functionality. None of the isolates showed a degree of 

selectivity comparable to that of antimalarial drugs such as chloroquine, 

quinine, mefloquine, and artemisinin (Likhitwitayawuid 

et al., 1993a,b). Six compounds from S. dinklagei Diels 

3.26. Stephania venosa (Blume) Spreng. 

(−)-O-acetylsukhodianine (78), kamaline, oxoaporphin, 

oxostephanosine (79), (−)-crebanine (7), dehydrocrebanine, 

(+)-N-carboxamidostepharine (80), (−)-kikemanine, 

(−)-tetrahydropalmatine (5), (−)-stepharinosine (81), (+)- 

stepharine (9), liriodenine (19), (−)-O-methylstepharinosine, 

oxocrebanine, dehydrostephanine, (−)-ushinsunine, oxostephanine, 

(−)-sukhodiamine, (−)-sukhodianine--N-oxide, 

(−)-stephadiolamine--N-oxide (Guinaudeau et al., 1981, 1982; 

Pharadai et al., 1985; Charles et al., 1987; Banerji et al., 1994; 

Likhitwitayawuid et al., 1999), stepharanine, cyclanoline and 

N-methyl stepholidine (Ingkaninan et al., 2006). 

including, two zwitterionic oxoaporphine alkaloids [Nmethylliriodendronine 

(22) and 2-O,N-dimethylliriodendronine 

(23)], two oxoaporphine alkaloids [liriodenine (19) and dicentrinone 

(20)], one aporphine alkaloid [corydine (21)] and one 

anthraquinone [aloe-emodine (24)] were tested for antiprotozoal 

and cytotoxic activity in vitro. N-methylliriodendronine was most 

active against Leishmania donovani amastigotes (IC 50 = 36.1 M). 

Liriodenine showed the highest activity against L. donovani, and 

P. falciparum with IC 50 values of 26.16 and 15 M, respectively. 

Aloe-emodin (24) was the only compound active (IC 50 =14M) 

against T.b. brucei (Camacho et al., 2000). The aqueous extract of 

leaves of S. abyssinica Walp. showed significant anti-plasmodial 

activity in vitro against chloroquine sensitive and resistant laboratory 

adapted strains of P. falciparum with IC 50 values >30 gmL −1 

(Muregi et al., 2004). 

4.2. Antimicrobial activity 

4. Biological activities 

4.1. Anti-malarial activity 

Four major alkaloids dehydroroemerine (DN), tetrahydropalmatine 

(TN) (5), xylopinine (XN) and cepharanthine (CN) (69) as 

A hasubanalactam alkaloid, glabradine (45) isolated from the 

tubers of S. glabra (Roxb.) Miers was evaluated for antimicrobial 

activity against Staphylococcus aureus, S. mutans, Microsporum 

gypseum, M. canis and Trichophyton rubrum and displayed potent 

antimicrobial activity superior to those of novobiocin and erythromycin 

with IZD values of 19–27 cm (Semwal and Rawat, 

2009a,b). An ethanolic extract was also evaluated for its antimicrobial 

activity against five bacterial species (S. aureus, S. mutans, S. 

epidermidis, Escherichia coli and Klebsiella pneumonia) and six fungal 

species (Aspergillus niger, A. fumigatus, Penicillum citranum, M. gypseum, 

M. canis and T. rubrum) and found to be active against most


of the tested microorganisms with MIC range of 50–100 g/mL 

(Semwal et al., 2009). The methanolic root extract of S. japonica 

(Thunb.) Miers showed significant in vitro activity together with 

Cissampelos pareira and Cyclea peltata (Hullatti and Sharada, 2007). 

Cepharanone D, N-formyl-asimilobine and N-formylannonain isolated 

from S. succifera H. S. Lo & Y. Tsoong showed significant 

antimicrobial activity in vitro (Yang et al., 2010a,b). 

4.3. Anthelmintic activity 

The alcoholic extract of the dried rhizome of S. glabra (Roxb.) 

Miers was tested against various helminth parasites, i.e. nematode 

(Heterakis gallinarum, Ascaridia galli, Ancylostoma ceylanicum and 

Ascaris suum), cestode (Raillietina echinobothrida) and trematode 

(Fasciolopsis buski) in dosages ranging between 25 and 100 mg/mL 

in 0.9% phosphate buffered saline (PBS, pH 7.2) at 38 ± 1 ◦ C. The 

controls, kept in PBS, survived for an average 22 h (trematode), 

72 h (cestode) and 55 > 380 h (nematodes). The results showed pronounced 

effect on the cestode and trematode, i.e. a dose-dependent 

gradual decline in physical motility was observed in R. echinobothrida 

and F. buski (Das et al., 2004). 

4.4. Anti-viral activity 

The antiviral activity of methanolic extract of S. cepharantha 

Hayata tubers, its chloroform soluble fraction (alkaloid fraction) 

and the major alkaloid FK-3000 were investigated in BALB/c mice 

cutaneously infected with HSV-1 strain 7401H. At oral doses of 

125 and 250 mg/kg body weight, the methanol extract significantly 

delayed skin lesions on score 2 (vesicles in the local region), limited 

the development of further lesions on score 6 (mild zosteriform 

lesion) and prolonged the mean survival time of HSV-1 infected 

mice. After administration of the alkaloid fraction at doses of 25 

and 50 mg/kg or FK-3000 at 10 and 25 mg/kg, similar results were 

obtained. Although the alkaloid improved the survival of infected 

mice, it had a narrow therapeutic index (Nawawi et al., 2001; Liu 

et al., 2004; Zhang et al., 2005). 

4.5. Anti-proliferative/anti-cancer activity 

Four alkaloids (dl-tetrandrine, fangchinoline (50), d-tetrandrine 

and d-isochondrodendrine) isolated from S. hernandifolia (Willd.) 

Walp. showed significant cytotoxicity against human carcinoma 

of the nasopharynx carried in tissue culture (KB), and that dltetradrine 

and d-tetrandrine showed significant inhibitory activity 

in vivo against the Walker 256 intramuscular carcinosarcoma in the 

rat (Kupchan et al., 1968). Ethanolic extract of S. venosa (Blume) 

Spreng. bulb was tested for antiproliferative activity against SKBR3 

human breast adenocarcinoma cell line using MTT assay and 

showed activity in potential range for further investigation on cancer 

cells (Moongkarndi et al., 2004). Aporphine alkaloid isolated 

from S. venosa (Blume) Spreng. exhibited antiproliferation activity 

on SKOV3 human ovarian cancer cell line using MTT assay. 

Aporphine showed strong inhibition activity with an ED 50 value 

of 6 g/mL (Montririttigri et al., 2008). Four bisbenzylisoquinoline 

alkaloids (cepharanthine (69), cepharanoline, isotetrandrine 

and berbamine) from S. cepharantha Hayata showed significant 

effects on proliferation of culture cell from the murine skin in 

the range of 0.01–0.1 g/mL (Nakaoji et al., 1997). Cepharanthine 

(CN) inhibits tumor promotion after topical application 

in two-stage carcinogenesis in mouse skin. Epidermal ornithine 

decarboxylase activities inhibited by topical application of CN, 

with 5 mg/mouse) and mezerein (5 mg/mouse) were found to 

be inhibited by topical application of CN, with a ED 50 values of 

1.2 mM and 1.4 mM, respectively. A diet containing 0.005% CN 

slightly suppressed the two-stage promotion of skin tumors by 

twice-weekly applications of 2.5 Mg TPA for 2 weeks (first stage) 

followed by twice-weekly applications of 2.5 Mg mezerein for 

23 weeks (second stage) in ICR mice following initiation by 50 

Mg 7,12-dimethylbenz[a]anthracene. Oral administration of CN 

inhibits the tumor promotion in two-stage carcinogenesis in mouse 

skin (Yasukawa et al., 1991). S. tetrandra S. Moore demonstrated 

antiproliferative and proapoptotic activities in a rat hepatic stellate 

cell line, HSC-T6 (Chor et al., 2005). The extract, as well as 

two aporphine alkaloids, (−)-asimilobine-2-O--D-glucoside and 

(−)-nordicentrine from S. pierrei Diels, and (+)-2-N-methyltelobine 

from S. errecta Craib showed potent cytotoxic activity against 

the KB (ED 50 3.6 g/mL) and P-388 (ED 50 0.8 g/mL) cell systems. 

It was found that the cytotoxicity of S. pierrei Diels was 

mainly due to the presence of the aporphine alkaloids containing 

the 1,2-methylenedioxy group (Likhitwitayawuid et al., 1993a,b; 

Angerhofer et al., 1999). Five compounds (7-oxodehydrocaaverine, 

7-oxocrebanine, dehydrocrebanine, crebanine and aristololactam 

I) from the tuber of S. succifera H. S. Lo & Y. Tsoong were evaluated 

for their cytotoxic activity by MTT assay. Dehydrocrebanine 

and crebanine showed inhibitory activity towards chronic myelogenous 

leukemia (K562), human gastric carcinoma (SGC-7901) 

and human hepatoma (SMMC-7721) cell lines (Yang et al., 2010a,b). 

Aqueous extract of S. venosa (Blume) Spreng. tubers was studied for 

cytotoxic activity on human peripheral blood mononuclear cells 

(PBMCs) and showed activity with IC 50 value of 300 mg/mL. The 

effect of the extract on apoptotic induction was also evaluated at the 

concentration of 300 mg/mL on PMBCs from healthy subjects and 

from cervical cancer patients and significantly induced apoptosis of 

the PBMCs from both healthy subjects and from the patients. The 

antiproliferative effect was also evaluated on the cells from healthy 

subjects and demonstrated activity with IC 50 value of 40 mg/mL 

(Sueblinvong et al., 2007). 

4.6. Antipsychotic activity 

(−)-Stepholidine (SPD) isolated from S. intermedia H. S. Lo, which 

binds to the dopamine D 1 and D 2 like receptors has been evaluated 

for its antipsychotic effects in animal models. The effects of 

SPD, clozapine and haloperidol in increasing forelimb and hindlimb 

retraction time in the paw test and in reversing the apomorphine 

and MK801-induced disruption of prepulse inhibition was investigated. 

In the paw test, clozapine and SPD increased the hind limb 

retraction time. In the prepulse inhibition paradigm, all three drugs 

reverse the apomorphine-induced disruption in prepulse inhibition, 

while none of the drugs could reverse the MK801-induced 

disruption. SPD even slightly, but significantly potentiated the 

effects of MK801 (Ellenbroek et al., 2006). 

4.7. Apoptosis inducing effect 

Apoptosis inducing effect of tetrandrine (TN), a bisbenzylisoquinoline 

alkaloid derived from S. tetrandra S. Moore on activated 

hepatic stellate cells of rat has been examined. The hepatic stellate 

cells transformed by Simian virus 4 (T-HSC/CL-6) to overcome 

the limitations inherent in studying primary cultures of hepatic 

stellate cells. TN treatment at doses of 25 and 50 g/mL for 

12 h induced apoptosis as confirmed by DNA fragmentation and 

increased sub-G1 DNA content. TN also induced the activation 

of capase-3 protease and subsequent proteolytic cleavage of poly 

(ADP-ribose) polymerase (Zhao et al., 2004). 

4.8. Multidrug resistance reversing activity 

An alkaloidal extract of the vines of S. japonica (Thunb.) Miers 

showed multidrug resistance reversing activity as demonstrated 

by the bicinchoninic acid assay. Insotrilobine and trilobine from


the plant were shown to be as active as verapamil (standard) 

in reversing doxorubicin resistance in human breast cancer cells 

(MCF-7 cells). Isotrilobine has MDR-reversing activity comparable 

to verapamil at concentrations less than the ED 20 of isotrilobine 

on MCF-7/ADR cells. Trilobine has low activity with a slope of 28 

as compared with slopes of 211 and 232 for isotrilobine and verapamil, 

respectively. The greater efficacy of isotrilobine to trilobine 

appears to be a result of the methyl group at N-2 ′ . This is the only 

structural difference between the two compounds and suggests 

that a tertiary amine is preferred at this position to a secondary 

amine. The slightly increased lipophilicity induced by the addition 

of another methyl group may also contribute to the increased 

activity (Hall and Chang, 1997). 

4.9. Anti-inflammatory and analgesic activity 

To investigate the anti-inflammatory effects of S. tetrandra 

S. Moore in vitro and in vivo, its effects on the production of 

IL-6 and inflammatory mediators were analyzed. When human 

monocytes/macrophages (stimulated with silica) were treated 

with 0.1–10 g/mL the plant, the production of IL-6 was inhibited 

up to 50%. It also suppressed the production of IL-6 by 

alveolar macrophages. In addition, it inhibited the release of 

superoxide anion and hydrogen peroxide from human monocytes/macrophages. 

To assess the anti-fibrosis effects of S. tetrandra, 

its effects on in vivo experimental inflammatory models were evaluated. 

In the experimental silicosis model, IL-6 activities in the 

sera and in the culture supernatants of pulmonary fibroblasts were 

also inhibited by it. In vitro and in vivo treatment with S. tetrandra 

reduced collagen production by rat lung fibroblasts and lung 

tissue. It also reduced the levels of serum GOT and GPT in the 

rat cirrhosis model induced by CCl 4 , and was effective in reducing 

hepatic fibrosis and nodular formation (Kang et al., 1996). The antiinflammatory 

constituents, tetrandrine (18) and fangchinoline (50) 

from S. tetrandra have been shown to decrease IL-1beta, IL-6, IL-8 

and TNF-alpha as well as decrease leukotriene and prostaglandin 

generation. Furthermore, tetrandrine has been shown to inhibit the 

production of TNF-alpha and IL-6 by microglial cells (Teh et al., 

1990; Xue et al., 2008). The combined analgesic effect of aconitum 

(Ac) and S. tetrandra (St) was found superior to that of Ac and St 

when used alone. The combined Ac-St showed remarkable analgesic 

activity within 3 h (p < 0.01) in rabbits and mice models (Li et 

al., 2000). 

4.10. Immunomodulating activity 

S. tetrandra S. Moore has been used to treat autoimmune 

diseases such as rheumatoid arthritis and systemic lupus erythe 

matosus. Tetrandrine (18) has potential immunomodulating 

and anti-inflammatory effects. T-lymphocytes play a critical 

role as autoactive and pathogenic population in autoimmune 

and inflammatory diseases. Some experimental data showed 

that, through down-regulating the protein kinase C (PKC) signaling, 

interleukin-2 secretion and the expression of the T 

cell activation antigen (CD71), tetrandrine inhibited phorbol 

12-myristate 13-acetate (PMA)+ionomycin-induced T cell proliferation 

dependent on interleukin-2 receptor chain and CD69, 

such an action was unrelated to Ca 2+ channel blockade (Ho 

et al., 1999). Tetrandrine (0.1–10 ML −1 ) significantly inhibited 

neutrophil-monocyte chemotactic factor-1 upregulation and 

adhesion to fibrinogen induced by N-formyl-methionyl-leucylphenylalanine 

and PMA. Tetrandrine at 0.1–100 ML −1 caused 

dose and time-dependent loss of cell viability of mouse peritoneal 

macrophages, guinea-pig alveolar macrophages and mouse 

macrophage-like J774 cells, reduced production of oxygen free 

radical, down-regulated synthesis and release of some proinflammatory 

cytokines (Pang and Hoult, 1997; Shen et al., 

1999). 

4.11. Antifibrotic effect 

Antifibrotic effect of a methanol extract from S. tetrandra S. 

Moore on experimental liver fibrosis has been investigated. Liver 

fibrosis was induced by bile duct ligation and scission (BDL/S) in 

rats. In BDL/S rats, activity levels of aspirate transaminase, alanine 

transaminase, alkaline phosphatase, concentration of total 

bilirubin in serum, and 100 mg/kg/day or 200 mg/kg/day, (p.o. for 

4 weeks) in BDL/S rats reduced the serum aspirate transaminase, 

alanine transaminase, alkaline phosphatase activity levels significantly 

(p < 0.01) (Nan et al., 2000). 

4.12. Anti-hyperglycemic effect 

The ethanolic extract of the tubers of S. glabra (Roxb.) Miers 

was evaluated for its hyperglycemic effects against alloxan-induced 

diabetic and significantly decreased the blood sugar level in experimental 

animals (Semwal et al., 2010a). A palmatine derivative, 

11-hydroxypalmatine (44) isolated from this plant was also evaluated 

for its anti-hyperglycemic activity. The test compound was 

administered at doses of 25, 50, and 100 mg/kg, p.o., 36 h after 

alloxan injection (60 mg/kg, i.v.). The alloxan-induced diabetic mice 

showed significant reduction in blood glucose after treatment with 

the test compound by 52% as compared to the positive control 

glibenclamide (54%) and the diabetic control (27%) (Semwal et al., 

2010b). S. tetrandra S. Moore roots increases the blood insulin level 

and reduces the blood glucose level in streptozotocin diabetic mice. 

Actions of bisbenzylisoquinoline alkaloids isolated from the plant 

were investigated in the hyperglycemia of diabetic mice. A main 

bisbenzylisoquinoline alkaloid fangchinolin (0.3–3 mg/kg) significantly 

reduced blood glucose level of the diabetic mice. The effect 

of fangchinoline was 3.9 fold greater than that of water extract 

(Tsutsumi et al., 2003). S. tetrandra has a direct effect on the retinal 

capillary of posterior ocular region and suppressed neovascularization 

of retinal capillary in streptozotocin diabetic rats through 

the activation of tetrandrine (Liang et al., 2002). The oral administration 

of ethanol and aqueous extract (400 mg/kg body weight) of 

powdered corm of S. hernandifolia significantly (p < 0.05) decreased 

the blood glucose of normal and Streptozotocin-induced diabetic 

rats up to 12 h. Glibenclamide was used as a standard drug at a dose 

of 0.25 mg/kg (Sharma et al., 2010). 

4.13. Ca 2+ channel blocking activity 

Abnormal Ca 2+ signaling and elevated concentration of intracellular 

free Ca 2+ are the basic pathophysiological events involved 

in various diseases. As a Ca 2+ antagonist, tetrandrine (S. tetrandra) 

can inhibit extracellular Ca 2+ entry, int ervene in the distribution 

of intracellular Ca 2+ , maintain intracellular Ca 2+ homeostasis, and 

then disrupt the pathological processes. As shown in whole cell 

patch-clamp recordings, tetrandrine blocked bovine chromaffin 

cells voltage-operated Ca 2+ channel current in a time and concentration 

dependently manner. In rat phaeochromocytoma PC 12 

cells, 100 mol L −1 tetrandrine abolished high K + (30 mmol L −1 ) 

-induced sustained increase in cytoplasmic Ca 2+ concentration, 

inhibited bombesin-induced inositol triphosphate accumulation in 

NIH/3T3 fibroblast and abolished Ca 2+ entry (Takemura et al., 1996). 

Tetrandrine can affect cardiovascular electrophysiologic properties 

by inhibit the contractility, ±dt/dp max , and automaticity of 

myocardium, prolong the FRP, and exert concentration-dependent 

negative inotropic and chronotropic effects without altering cardiac 

excitability. Tetrandrine directly blocks both T-type and L-type 

calcium current in ventricular cells and vascular smooth muscle


cells, but it does not shift the I–V relationship curve of I Ca . All its 

effects would be beneficial in the treatment of angina, arrhythmias, 

and other cardiovascular disorders. It also directly inhibits 

the activity of BK Ca channel in endothelial cell line and also inhibits 

Ca 2+ -release-activated channels in vessel endothelial cells, which 

might significantly contribute to the change of endothelial cell 

activity (Qian, 2002; Yao and Jiang, 2002). 

4.14. Acetylcholinesterase (AChE) inhibitory activity 

Three quaternary protoberberine alkaloids, stepharanine, 

cyclanoline and N-methyl stepholidine from S. venosa (Blume) 

Spreng. tuber expressed inhibitory activity on AChE with IC 50 values 

of 14.10, 9.23 and 31.30 M, respectively. The AChE inhibitory 

(potential drugs for Alzheimer’s disease) activity of these compounds 

was compared with those of the related compounds, 

palmatine, jatrorrhizine and berberine, as well as with tertiary protoberberine 

alkaloids, stepholidine and corydalmine isolated from 

the same plant. The results suggest that the positive charge at the 

nitrogen of the tetrahydroisoquinoline portion, steric substitution 

at the nitrogen, planarity of the molecule or substitutions at C-2, 

-3, -9, and -10 affect the AChE inhibitory activity of protoberberine 

alkaloids (Ingkaninan et al., 2006). The ethanolic extract of roots 

along with the alkaloids isolated from S. rotunda Lour. showed significant 

AChE inhibitory activity (in vitro) using a rat cortex AChE 

enzyme (Hung et al., 2010). 

4.15. Vasodilating and hypotensive activities 

Comparative studies of the effects of tetrandrine (TN) and 

fangchinoline (FN), two major components of the Radix of S. 

tetrandra S. Moore, on vasodilations and on calcium movement 

in vascular smooth muscle, and studies of hypotensive effects 

on stroke-prone spontaneously hypertensive rats (SHRSP) were 

performed. TN and FN inhibited high K + (65.4 mM) and induced 

sustained contraction in the rat aorta smooth muscle strips. IC 50 

values for TN and FN were 0.27 ± 0.05 M and 9.53 ± 1.57 m, 

respectively, and this inhibition was antagonized by increasing 

the Ca 2+ concentration in the medium. The IC 50 of TN 

for norepinephrine (NE)-induced contraction (0.86 ± 0.04 g) was 

3.08 ± 0.05 m, and the IC 50 of FN for NE-induced contraction 

(0.88 ± 0.07 g) was 14.20 ± 0.40 M. At the molecular level, radiolabelled 

45 Ca 2+ uptake tests revealed that TN and FN also inhibited 

high K + (65.4 mM) and 1 M NE-stimulated Ca 2+ influx in rat aorta 

strips at the maximal concentration was needed to inhibit the 

contraction. TN (3 mg/kg) and FN (30 mg/kg) administered by i.v. 

bolus injection also lowered the mean arterial pressure (MAP) significantly 

during the period of observation in conscious SHRSP, 

respectively. These results showed that TN was more potent than 

FN in blocking calcium channels and antihypertensive activity. The 

compounds were also shown to have hypotensive effects on stroke 

prone spontaneously hypertensive rats (Kim et al., 1997). 

4.16. Inhibition of antinociceptive effect 

Fangchinoline (FN), a non-specific calcium antagonist, from S. 

tetrandra S. Moore showed antagonistic activity on morphineinduced 

antinociception in mice. It has been found that FN (IP) 

attenuated morphine (SC)-induced antinociception in a dosedependent 

manner with significant effect at doses of 30 and 

60 mg/kg body wt (IP) in the tail-flick test but not the tailpinch 

tests. This antagonism was abolished by pretreatment 

with a serotonin precursor, 5-hydroxytryptophan (5-HTP, IP), 

but not by pretreatment with a noradrenaline precursor, L- 

dihydroxyphenylalanine (L-DOPA, IP) in the tail-flick test. The 

serotonergic pathway may be involved in the antagonism of 

morphine-induced antinociception by FN and, in agreement with 

other reports, also indicates the possible dissociation of the morphine 

analgesic effect from its tolerance-development mechanism 

(Fang et al., 2005). 

4.17. Acute hemodynamic effect 

Acute hemodynamic effect of tetrandrine, isolated from S. 

tetrandra was assessed in anesthetized cirrhotic rats. Tetrandrine 

decreases of PVP and MAP, the maximum percentage reduction of 

PVP after drug was 5.4 ± 1.0%, 9.2 ± 0.8% and 23.7 ± 1.2% of base 

line, respectively, for the doses given 2.0, 6.6 and 20.0 mg/kg. Total 

peripheral resistance was also reduced by the drug (Huang et al., 

1999). 

4.18. Histamine release inhibition activity 

Bisbenzylisoquinoline alkaloids from S. cepharantha Hayata 

roots and tubers were tested for histamine release inhibition 

assay. The order of the potency of inhibitory effect was ranked 

as homoaromoline, aromoline, isotetrandrine, cepharanthine (69), 

fangchinoline (50), obaberine and tetrandrine (Nakamura et al., 

1992). 

4.19. Antioxidant activity 

Fangchinoline (50) and cepharanthine (69) isolated from S. 

rotunda Lour. performing different in vitro antioxidant assays, 

including 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical 

scavenging, 2,2 ′ -azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) 

(ABTS) radical scavenging, N,N-dimethyl-p-phenylenediamine 

dihydrochloride (DMPD) radical scavenging, superoxide anion 

(O 2 •− ) radical scavenging, hydrogen peroxide scavenging, total 

antioxidant activity, reducing power, and ferrous ion (Fe 2+ ) chelating 

activities. Cepharanthine and fangchinoline showed 94.6 and 

93.3% inhibition on lipid peroxidation of linoleic acid emulsion 

at 30 g/mL concentration, respectively. On the other hand, 

butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), 

-tocopherol, and trolox indicated inhibitions of 83.3, 92.2, 72.4, 

and 81.3% on peroxidation of linoleic acid emulsion at the same 

concentration (30 g/mL), respectively (Gulcin et al., 2010). The 

ethanol and aqueous extracts (400 mg/kg body weight) of powdered 

corm of S. hernandifolia (Willd.) Walp. strongly scavenged 

DPPH radicals with IC 50 values of 265.33 and 217.90 g/mL, respectively 

in vitro whereas the superoxide radical were scavenged with 

IC 50 values of 526.87 and 440.89 g/mL, respectively. Ascorbic acid, 

a natural antioxidant, was used as positive control (Sharma et al., 

2010). 

4.20. Miscellaneous uses 

Tetrandrine (TN) from the root of S. tetrandra S Moore has been 

used to treat silicosis. Except for its antiinflammatory, antifibrogenetic, 

immunomodulating effects and antioxidant effects, TN 

shows antiallergic effects, inhibitory effects on pulmonary vessels 

and airway smooth muscle contraction, and platelet aggregation 

via its nonspecific calcium channel antagonism that suggested its 

potential in the treatment of asthma, pulmonary hypertension and 

chronic obstructive pulmonary disease (Xie et al., 2002). TN has 

been used to treat silicosis, autoimmune disorders, and hypertension 

in Mainland China for decades. The accumulated studies 

both in vitro and in vivo reveal that it preserves a wide variety 

of immunosuppressive effects. Importantly, the TN-mediated 

immunosuppressive mechanisms are evidently different from 

some known DMARDs. The synergistic effects have also been 

demonstrated between TN and other DMARDs like FK506 and


cyclosporin. TN is a very potential candidate to be considered as one 

of DMARDs in the treatment of autoimmune diseases, especially 

rheumatoid arthritis (Lai, 2002). The stem extract of S. cepharantha 

Hayata (SC) was evaluated for its toxicity, bacteriostatic, antiphlogistic 

and antalgic activity. For toxicity, SC administered to mice by 

i.v. and i.p. routes in solution in physiological serum (water containing 

9 g/L of NaCl) is well tolerated and LD 0 (maximum non-lethal 

dose) was found higher than 500 mg/kg. SC exhibits a bacteriostatic 

activity against Gram (+) and Gram (−) bacteria. For instance 

the MIC values are 2 mg/mL on Staphylococcus aureus London and 

44 mg/mL on a strain of Proteus. The antiphlogistic activity of SC 

was studied on female rats by using phenylbutazone as a positive 

control and inhibits in a statistically significant manner the development 

of the carrageen oedema at 100 mg/kg, the action being 

maximum 3 h after administration. The antalgic activity was carried 

out by i.p. administration of SC and aspirin (standard) to male 

mice of 0.2 mL of an aqueous solution of acetic acid (30 g/L) and 

showed significant results (Debat et al., 1980). Two aporphine alkaloids, 

corydine (21) and atherospermidine isolated from ethanolic 

extract of the stems of S. dinklagei Diels showed DNA damaging 

activity (Goren et al., 2003). Levo-tetrahydropalmatine (l-THP), an 

alkaloid constituent found in many plants of genus Stephania produced 

a rightward and downward shift in the dose–response curve 

for cocaine self-administration and attenuated cocaine-induced 

reinstatement. l-THP also reduced food-reinforced responding and 

locomotor activity (Mantsch et al., 2007). The effects of a leaf extract 

of S. hernandifolia on testicular activities in albino rats at the dose 

of 2 g or 4 g of leaves/mL distilled water/100 g body weight/day 

for 28 days was studied. Treatment with both doses resulted in 

significant reduction in relative weight in the testis, the seminal 

vesicles, the prostate, and the epididymis without any significant 

change in the liver and kidney weight. The extract reduced the 

activities of testicular androgenic key enzymes and plasma level of 

testosterone along with inhibition of spermatogenesis without any 

induction of hepatic and renal toxicity (Ghosh et al., 2002; Jana et al., 

2003). 

4.21. Toxic effects 

Apart from various medicinal uses, rare plants of the genus 

Stephania have been reported for their acute toxic effects. The 

oral administration of aqueous extract of wet and dry root tuber 

of Stephania cepharantha Hayata showed acute toxicity with LD 50 

value of 41.4 g/kg and 22.9 g/kg, respectively (Chen et al., 1999). S. 

cephalantha Hayata (root tubers) and S. epigaea H.S. Lo (root tubers) 

have been recognized as toxic plants in China (Huai et al., 2010). S. 

sinica (an shu ling) was shown to have hepatotoxicity (Haller et al., 

2002). 

5. Future perspectives and conclusion 

Although, an extensive amount of research work has been done 

on some plants of this genus to date, but a large number of species 

are still chemically and/or pharmacologically unknown such as 

S. brevipes Craib, S. tomentella Forman, S. glandulifera Miers and 

S. capitata (Blume) Spreng. Consequently, a broad field of future 

research remains possible in which the isolation of new active principles 

from these species would be of great scientific merit. The 

alkaloids are of particular interest as many are highly potent bioactives 

and perhaps responsible for most of activities shown by 

the plants of this genus. However, the mechanism of their action 

is still unknown. Hence, a detailed study is required to understand 

the structure–activity relationship of these constituents. As literature 

showed, many plant extracts having cytotoxic activity, hence, 

the particular constituent responsible for the activity may be isolated 

for further process. In addition, some plant extracts were only 

screened for their preliminary in vitro activities, so, the advance 

clinical trial of them deserves to be further investigated. Herein, 

we described the possible applications in clinical research but further 

investigations on phytochemical discovery and subsequent 

screening are needed for opening new opportunities to develop 

pharmaceuticals based on Stephania constituents. 

Acknowledgements 

This work was financially supported by UGC New Delhi under 

the Dr. D.S. Kothari Post Doctoral Fellowship Scheme. The authors 

pay their sincere thanks to editor and referees of the journal, for 

their valuable suggestions to improve this article. 

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The genus Stephania - Dr. DS Kothari Postdoctoral Fellowship ...

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