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Antitussive, expectorant, and bronchodilating effects of quinazoline alkaloids ([+ or -])-vasicine, deoxyvasicine, and ([+ or -])-vasicinone from aerial parts of Peganum harmala L.

Introduction

Cough is among the common symptoms associated with many respiratory diseases, such as asthma, chronic bronchitis, and pneumonia (Ce et al., 2009; Irwing and Madison, 2000). These respiratory diseases are usually treated with antitussives, expectorants, mucoiytics, bronchodilators, and glucocorticoids (Perez et al., 2008). However, the available therapies for cough lack effectiveness, and therefore, the patients continue suffering from cough (Wang et al., 2012; Zhang et al., 2009). Many herbs of traditional Chinese medicines have been used for hundreds of years to treat respiratory complaints, such as cough, asthma, expectoration, bronchial inflammatory, and pneumonia; these medicines have showed less or no side effects compared with synthetic drugs (Dorsch and Wagner, 1991 ; Jiangsu New Medical College, 1977; Shang et al., 2010). However, traditional Chinese medicines are not accepted as therapeutic agents in many advanced countries because of insufficient chemical and pharmacological investigations conducted on them (Newman and Cragg, 2007; Shang et al., 2010).

Peganum harmala L. (Zygophyllaceae) grows spontaneously in the arid and semiarid areas North-West China and is also found in North Africa and the Middle East (Cheng et al., 2010; Farouk et al., 2008). The seeds and the aerial parts of P. harmala (APP) have been commonly used as traditional folk medicine to treat various ailments, including cough, asthma, rheumatism, hypertension, diabetes, and jaundice in the Xinjiang Uygur and Mongolian Autonomous Regions of China (Chinese Pharmacopoeia Committee, 1998; Zheng et al., 2009). This plant is also a well-known and effective herbal medicine in Turkey, Iran, Algeria, and Morocco (Bensalem et al., 2014; Farouk et al., 2008; Hemmateenejad et al., 2006). Previous phytochemical studies showed that quinazoline alkaloids and flavonoids are the major constituents of APP, and among alkaloids, vasicine (VAS) and deoxyvasicine (DVAS) are the main ones. Of them, VAS can be spontaneously oxidized to vasicinone (VAO) (Duan et al., 1998; Liu et al., 2015b; Rachana et al., 2011; Sharma et al., 1983). Previous in vitro studies showed that the crude extracts of APP, containing VAS, DVAS, harmine and harmaline, may have effective anti-asthmatic activities (Amin and Mehta, 1959; Hider et al., 1981 ; Nie et al., 2004). Our previous pharmacological studies in vivo showed that the alkaloid fraction of APP have remarkable antitussive, expectorant and bronchodilating activities (Liu et al., 2015a). However, further in vivo studies of relevant alkaloids of these species are lacking. Therefore, a series of experiments was designed to evaluate the antitussive, expectorant, and bronchodilating effects of the three quinazoline alkaloids VAS, DVAS and VAO, in an attempt to confirm whether they are the main active compounds in APP.

Materials and methods

Reagents

Codeine phosphate, phenol red, ammonium chloride, ammonia, hydrogen peroxide, acetone, ethanol, methanol, and ethyl acetate were purchased from Sinopharm Chemical Reagent Co., Ltd (Shanghai, China). Capsaicin, aminophylline, acetylcholine chloride, and histamine phosphate were purchased from Sigma-Aldrich Co. (St. Louis, MO, USA). Standard compounds VAS, DVAS, and VAO were isolated previously from APP in our laboratory and were characterized by NMR and mass spectral data, and these values were compared with those in the literature. The purities of these compounds were determined to be more than 98% by a previously reported HPLC analysis method (Wen et al., 2014).

Collection and preparation of plant material

APP was collected in Urumqi, Xinjiang Province, China in August 2011 and authenticated by Chang-hong Wang, professor of the Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine. Fresh herbs were dried in the shade for one week. The voucher specimens (Voucher number: PH-XJ1104) were deposited at the Herbarium of Shanghai R&D Center for Standardization of Traditional Chinese, Shanghai, China.

Extraction

Dried APP (2500 g) was cut into segments and extracted with 501 of 50% ethanol (v/v) (x 3) in reflux for 2 h. Solutions were combined, filtered, and concentrated under reduced pressure at 45[degrees]C to afford 101 of APP concentrated extract. The solution of concentrated extract was used to prepare the alkaloid fraction (50.8 g) by macroporous resin column chromatography (15 cm x 150 cm; 4 1). The following process was carried out as described previously (Liu et al., 2015a).

Isolation of VAS and DVAS by column chromatography

A portion of the above alkaloid fraction (40 g) was chromatographed over silica gel (100-200 mesh) and eluted with methanol-dichloromethane-ammonia mixtures (3:2:0.1). ([+ or -])-VAS and DVAS were successively eluted and obtained after evaporation under reduced pressure at 45[degrees]C. VAS and DVAS respectively provided a single spot on TLC over silica gel at Rf = 0.52 and Rf = 0.41, respectively, with methanol-dichloromethane-ammonia mixtures (3:2:0.1) as the developing system, and the spots turned orange red upon spraying with Dragendorffs reagent. The actual structures of VAS and DVAS were characterized by NMR data, mass spectral data, and by comparing with standard compounds (Plugar et al., 1983; Liu et al., 2015b).

Oxidation of VAS to VAO by hydrogen peroxide

VAS (5 g) was dissolved in 100 ml of acetone and heated into a 1000 ml glass beaker at 90[degrees]C in a water bath. Hydrogen peroxide 30% (200 ml) was added to the mixture, stirred well, and heated in a water bath (90[degrees]C) for 60 min. The mixture was then poured into water (200 ml). The mixed solution was evaporated under reduced pressure at 45[degrees]C. Then, ([+ or -])-VAO was isolated and purified by preparative HPLC performed with a CAPCELL PAK C18 MG II (20 mm x 250 mm, 5 p.m, SHISEIDO CO., Japan) at 30[degrees]C in a LC3000 liquid chromatograph (Beijing Tong Heng Innovation Technology Co., Beijing, China). The isocratic mobile phase (at a flow rate of 15 ml/min) consisted of methanol (A) and 0.1% aqueous formic acid (B). The detection wavelength was set at 280 nm. VAO (522 mg) was characterized by NMR data, mass spectral data, and by comparison with standard compounds (Liu et al., 2015b). The structures of VAS, DVAS and VAO are showed in Fig. 1.

Animals and drug administration

All animals including the Institute for Cancer Research (ICR) mice of either sex, body weight 20-25 g (for ammonia or capsaicin induced cough studies); ICR mice of either sex, body weight 20-25 g (for phenol red secretion study) and guinea pigs of either sex, body weight 200-300 g (for citric acid-induced guinea pigs cough experiment and bronchodilating tests) were purchased from Experimental Animal Center, Shanghai University of Traditional Chinese Medicine, China.

All animals were housed with free access to food and water. The animals were maintained on a 12 h light-dark cycles (light on from 7:00 to 19:00) at environmental temperature (22[degrees]C-24[degrees]C) and 6065% relative humidity for 7 d. Before the experiments, all animals were fasted for 12 h and fed with water. All animal experimental protocols were in accordance with the regulations of experimental animal administration issued by the State Committee of Science and Technology of People's Republic of China on 14 November 1988.

Several doses of VAS, VAO, and DVAS were dissolved and diluted with 0.5% carboxymethylcellulose (CMC-Na) solution, and 3.6% hydrochloric acid was the pH regulator. Treatments were carried out orally.

Antitussive activity against ammonia-induced mice cough

Ammonia-induced mice cough tests were carried out as described previously (Wang et al., 2012) with slight modifications. Mice (110) were numbered and individually placed into a 500 ml special glass chamber which was positioned upside down. These mice were exposed to 0.1 ml of 25% ammonia solution (loaded in a glass plate, diameter 28 mm, height 10 mm) for 45 s. The latency period (the period from the start to the onset of cough) and the coughing frequency in 2 min were recorded by a trained observer. During observation, only typical cough reflection, which was characterized by obvious contraction of the abdominal cavity and successively distinctive opening of mouth, was counted. After 24 h recovery, these mice were randomly divided into 11 groups of 10 mice. Animals in group 1 were administered with 0.5% CMC-Na. Animals in group 2 (positive control) received 30 mg/kg of codeine phosphate. Animals in groups 3-5 were treated with 5,15, and 45 mg/kg of VAS. Animals in groups 6-8 were treated with 5, 15, and 45 mg/kg of VAO. Animals in groups 9-11 were treated with 5,15, and 45 mg/kg of DVAS. One h after administration, ammonia-exposure treatment was repeated on mice, and all the protocols were strictly the same as those in the first round. The latency period and the coughing frequency before and after treatment were compared.

Antitussive activity against capsaicin-induced mice cough

Capsaicin-induced mice cough tests were performed as previously described (Zhang et al., 2009) with slight modifications. Briefly, mice (110) were placed individually into a 500 ml special glass chamber and sprayed with the nebulized capsaicin solution (100 [micro]mol/l) for 10 s. The latency period and the coughing frequency in 2 min were recorded. After 24 h recovery, these mice were divided into 11 groups of 10 each, randomly. Animals in group 1 were administered with 0.5% CMC-Na. Animals in group 2 (positive control) received 30 mg/kg of codeine phosphate. Animals in groups 3-5 were treated with 5,15, and 45 mg/kg of VAS. Animals in groups 6-8 were treated with 5,15, and 45 mg/kg of VAO. Animals in groups 9-11 were treated with 5, 15, and 45 mg/kg of DVAS. One h after administration, mice were re-exposed to capsaicin treatment, and all the protocols were strictly the same as those in the first round. The latency period and the coughing frequency before and after treatment were compared.

Antitussive activity against citric acid-induced guinea pigs cough

This study was carried out as previously reported (Ge et al., 2009) with slight modifications. Guinea pigs (110) were placed individually into a 3 1 transparent chamber and then sprayed with 33% citric acid solution for 1 min. The period of the first cough since spraying (latency period) and the coughing frequency in 5 min were recorded. Only animals with a coughing frequency between 8 and 30 were included in the next round of evaluation. After 24 h of recovery, these guinea pigs were divided into 11 groups of 10 guinea pigs randomly. Animals in group 1 were treated with 0.5% CMC-Na. Animals in group 2 (positive control) received 30 mg/kg of codeine phosphate. Animals in groups 3-5 were treated with 5,15, and 45 mg/kg of VAS. Animals in groups 6-8 were treated with 5,15, and 45 mg/kg of VAO. Animals in groups 9-11 were treated with 5,15, and 45 mg/kg of DVAS. The second round of antitussive test was performed just 1 h after administration, and all the protocols were strictly the same as those in the first round. The latency period and the coughing frequency before and after treatment were compared.

Expectorant activity

Phenol red secretion experiments were carried out as described (Han et al., 2010) to evaluate the expectorant activities of VAS, VAO, and DVAS. Mice (110) were divided into 11 groups of 10 randomly. Animals in group 1 were administrated with 0.5% CMC-Na. Animals in group 2 (positive control) received 1500 mg/kg of ammonium chloride. Animals in groups 3-5 were treated with 5,15, and 45 mg/kg of VAS. Animals in groups 6-8 were treated with 5,15, and 45 mg/kg of VAO. Animals in groups 9-11 were treated with 5,15, and 45 mg/kg of DVAS. Thirty min after administration, mice were injected with 5% phenol red physiological saline solution (500 mg/kg) intraperitoneally. Another 30 min later, mice were sacrificed without damaging the tracheas. The trachea between the thyroid cartilage and the main stem bronchi was removed and placed into 1.5 ml of physiological saline solution. The solution was sonicated (30 min) to dissolve the phenol red. Then, 100 [micro]l of solution was removed into 96-wells and placed into 100 [micro]l of 0.1 M sodium hydroxide. Optical density of the mixture was measured immediately at 546 nm on a microplate reader (Power wave XS, Bio-Tek Instruments, Winooski, VT, USA). The amount of phenol red was calculated by the regression curve that was developed from a series of concentrations of phenol red at 546 nm on a microplate reader.

Bronchodilating activity

To evaluate the bronchodilating activity of VAS, VAO, and DVAS, a bronchoconstrictive test induced by acetylcholine chloride and histamine in guinea pigs was used (Xu et al., 1991). Briefly, guinea pigs (110, 200-300 g) of either sex were placed individually into a 31 glass chamber and were sprayed with the solution mixture of 2% acetylcholine chloride and 0.1% histamine (1:1, v/v) for 20 s. The time from the spraying of solution to the onset of tumble was recorded (pre-convulsive time). Animals with pre-convulsive times between 30 and 120 s were considered eligible. After 24 h of recovery, eligible animals (110) were divided randomly into 11 groups. Animals in group 1 were treated with 0.5% CMC-Na. Animals in group 2 (positive control) received 50 mg/kg of aminophylline. Animals in groups 3-5 were treated with 5,15, and 45 mg/kg of VAS. Animals in groups 6-8 were treated with 5, 15, and 45 mg/kg of VAO. Animals in groups 9-11 were treated with 5,15, and 45 mg/kg of DVAS. One h after administration, guinea pigs were subjected to bronchoconstrictive treatment again.

Statistical analysis

Data were expressed as mean [+ or -] standard error (S.E.M). Paired sample t test was used to evaluate the differences between results before and after drug administration in the same group. Statistical significance of differences between different groups was assessed by one-way analysis of variance. All calculations were conducted in the SPSS 18.0. A level of P < 0.05 was considered statistically significant.

Results

Antitussive effects

The effects of VAS, VAO, and DVAS on ammonia-induced mice cough are showed in Fig. 2. The coughing frequencies within 2 min were decreased by 24.97%, 42.99%, and 41.69% by VAS treatment at dosages of 5, 15, and 45 mg/kg (P < 0.05), by 28.24%, 35.98%, and 32.07% by VAO treatment at dosages of 5,15, and 45 mg/kg (P < 0.05), and by 36.36%, 43.70%, and 44.835% by DVAS treatment at dosages of 5,15, and 45 mg/kg (P < 0.05), respectively, compared with the frequency before drug administration. The coughing frequency was decreased by 41.99% by treatment with codeine phosphate (30 mg/kg) under the same conditions. In addition, compared with the coughing frequency of control mice after administration, all groups submitted to VAS, VAO and DVAS showed significant decreases in coughing frequency (Fig. 2A, P < 0.05). The latency periods were significantly prolonged for 66.93%, 41.06% and 105.83% by treatment with VAS at dosages of 5, 15, and 45 mg/kg (P < 0.05); for 84.30%, 86.32% and 148.00% by treatment with VAO at dosages of 5,15, and 45 mg/kg (P < 0.05), and for 53.66%, 57.48% and 102.13% by treatment with DVAS at dosages of 5,15, and 45 mg/kg (P < 0.05), respectively, compared with that before treatment. However, the latency period was only prolonged by 65.78% by codeine phosphate treatment at 30 mg/kg. Thus, VAS, VAO, and DVAS were more effective than codeine phosphate at high doses. In addition, all mice treated with VAS, VAO, and DVAS exhibited significant differences compared with control mice (Fig. 2B).

The effects of VAS, VAO, and DVAS on capsaicin-induced coughing mice are showed in Fig. 3. The coughing frequency within 2 min decreased by 20.42%, 25.35%, and 33.57% after treatment with VAS at dosages of 5,15, and 45 mg/kg (P < 0.05); by 19.93%, 28.80%, and 30.75% after treatment with VAO at dosages of 5, 15, and 45 mg/kg (P < 0.05); and by 16.54%, 22.44%, and 24.51% after treatment with DVAS at dosages of 5,15, and 45 mg/kg (P < 0.05), respectively, compared with that before treatment. Codeine phosphate (30 mg/kg) decreased the coughing frequency by 44.37%. In addition, compared with the coughing frequency of the control group, that of the VAS, VAO, and DVAS treatment groups significantly decreased (P < 0.05, Fig. 3A). Also, the latency periods were significantly prolonged by 33.60%, 50.26%, and 70.13% after treatment with VAS at dosages of 5, 15, and 45 mg/kg (P < 0.05); by 39.84%, 49.75%, and 75.32% after treatment with VAO at dosages of 5,15, and 45 mg/kg; and by 33.51 %, 41.88%, and 35.17% after treatment with DVAS at dosages of 5,15, and 45 mg/kg (P < 0.05, Fig. 3B), respectively, compared with that before treatment. By contrast, codeine phosphate (30 mg/kg) prolonged the latency period by 72.65%. In addition, all mice treated with VAS, VAO, and DVAS exhibited significant differences compared with control mice (P < 0.05, Fig. 3).

The antitussive effects of VAS, VAO, and DVAS in guinea pigs are showed in Fig. 4. Compared with that before treatment, coughing frequency in 5 min have been significantly decreased for 37.24%, 47.37%, 63.61% by treatment with VAS at dosages of 5, 15, and 45 mg/kg (P < 0.05); for 53.76% and 73.01% by treatment with VAO at dosages of 15, and 45 mg/kg (P < 0.05); and for 37.94% and 50.48% by treatments with DVAS at dosages of 15 and 45 mg/kg (P < 0.05), respectively. Codeine phosphate (30 mg/kg) decreased the coughing frequency by 73.53%. In addition, compared with that of control group, except for low doses of DVAS treatment group, the coughing frequency in all of the remaining VAS, VAO, and DVAS treatment groups are significantly decreased (P < 0.05) (Fig. 4A). Meanwhile, the latency period is prolonged for 47.37% and 64.93% by treatment with VAS at dosages of 15 and 45 mg/kg (P < 0.05); for 105.75% and 111.55% by treatment with VAO at dosages of 15 and 45 mg/kg; and for 59.02% and 59.08% by treatment with DVAS at dosages of 15 and 45 mg/kg (P < 0.05), respectively, compared with that before treatment. The latency period is prolonged for 88.28% after treatment by codeine phosphate (30 mg/kg). This finding indicated that the antitussive effects of VAO at middle and high dosages were much better than that of codeine phosphate. In addition, the latency period was significantly prolonged after treatment with middle and high doses of VAS, VAO, and DVAS (P < 0.05, Fig. 4B) compared with the latency period in control mice.

Expectorant activity

Expectorant activities were studied by measuring the amount of phenol red secretion in mice tracheas, and the results are given in Fig. 5. The amount of phenol red secretion significantly increased in mice by 0.54-, 0.79-, and 0.97-fold after treatment with VAS at dosages of 5,15, and 45 mg/kg (P < 0.05); by 0.60-, 0.99-, and 1.06-fold after treatment with VAO at dosages of 5, 15, and 45 mg/kg (P < 0.05); and by 0.46-, 0.73-, and 0.96-fold after treatment with DVAS at dosages of 5,15, and 45 mg/kg (P < 0.05) compared with that of the control group. The amount of phenol red secretion increased by 0.97-fold after treatment with standard expectorant drug ammonium chloride (1500 mg/kg) compared with that of the control group. The effects of VAO at of 15 and 45 mg/kg were even better than those of ammonium chloride (1500 mg/kg). This finding indicated that the expectorant effects of VAO (which is an oxidized or metabolized product from VAS) were strong.

Bronchodilating activity

The bronchodilating effects of VAS, VAO, and DVAS in guinea pigs are showed in Fig. 6. On average, standard bronchodilating drug aminophylline prolonged the pre-convulsive time in guinea pigs by 46.98%. The pre-convulsive time was prolonged for 19.70%, 19.46%, and 28.59% after treatments with VAS at dosages of 5, 15, and 45 mg/kg; for 28.87%, 10.82%, and 57.21% after treatment with VAO at dosages of 5,15, and 45 mg/kg; and for 2.31%, 11.11%, and 29.66% after treatment with DVAS at dosages of 5, 15, and 45 mg/kg, respectively, compared with that before treatment. VAS at high doses, VAO at low and high doses, and DVAS at high doses significantly prolonged the pre-convulsive time (P < 0.05), compared with that before treatment.

Discussion

As a traditional folk medicine, the seeds of P. harmala and APP were used to treat various diseases, including cough, asthma, rheumatism, hypertension, diabetes, and jaundice in the Xinjiang Uygur and Mongolian Autonomous Regions of China for a long time (Chinese Pharmacopoeia Committee, 1998; Zheng et al., 2009). In terms of main active components alkaloids, the seeds of P. harmala are rich in /S-carboline alkaloids harmine, harmane, and harmaline which showed to possess hallucinogenic effects (Araujo et al., 2015; Cheng et al., 2010) and are lacking in quinazoline alkaloids, namely, VAS, DVAS, and VAO. By contrast, APP mainly contain the quinazoline alkaloids (VAS, DVAS, and VAO) and contain only trace amounts of ficarboline alkaloids harmine, harmane, and harmaline (Cheng et al., 2010; Liu et al., 2013; Wang et al., 2002; Wen et al., 2014). The fact that APP contains only trace amounts of them, APP appears suitable for the development of an antitussive and expectorant phytomedicine in the future.

In all three antitussive models, the VAS, VAO, and DVAS significantly inhibited coughing frequency and prolonged the cough latency period in animals in a dose-dependent manner. Moreover, high doses of VAS, VAO, and DVAS (45 mg/kg) could produce satisfactory therapeutic activities that are as good as those of codeine phosphate (30 mg/kg) in mice and guinea pigs. In general, VAS, VAO, and DVAS have showed similar effects on the inhibition of coughing frequency. However, VAO has showed more potential than VAS and DVAS in prolonging the cough latency period, especially in guinea pigs cough models induced by citric acid.

In the bronchodilating test, VAS, VAO, and DVAS significantly prolonged the pre-convulsive times in guinea pigs and showed potent bronchodilating effects. The effect of VAO at high doses was stronger than that of aminophylline, which indicated that VAO could be a potent candidate drug or semi-synthetic material for treating bronchial asthma. VAS, DVAS and VAO provided the material basis for the bronchodilating effects of APP alkaloids in a previous study (Liu et al., 2015a).

Conclusion

In conclusion, results of pharmacological evaluation of antitussive, expectorant, and bronchodilating effects confirmed that VAS, VAO, and DVAS were active ingredients of the crude alkaloids extracted from APP.

http://dx.doi.org/10.1016/j.phymed.2015.08.005

ARTICLE INFO

Article history:

Received 10 March 2015

Revised 4 August 2015

Accepted 12 August 2015

Conflict of interest

The authors) declare(s) that there is no conflict of interests regarding the publication of this article.

Acknowledgment

The authors gratefully acknowledge the award from the Key Projects of Joint Funds of the National Natural Science Foundation of China and Xinjiang Uygur Autonomous Region of China (No. U1130303), the National Natural Science Foundation of China (Grant 81173119), the National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program", China (Grants 2012ZX0910320-051), and the Program of Shanghai Subject Chief Scientist (13XD1403500) awarded to Professor Chang-hong Wang for financial support of this study.

References

Amin, A.H., Mehta, D.H., 1959. A bronchodilator alkaloid (vasicinone) from Adhatoda vasica Nees. Nature 184,1317.

Araujo, A.M., Carvalho, E, Bastos, M.L., Guedes de Pinho, P., Carvalho, M., 2015. The hallucinogenic world of tryptamines: an updated review. Arch. Toxicol. 89, 1151-1173.

Bensalem, S., Soubhye, J., Aldib, 1., Bournine, L, Nguyen. A.T., Vanhaeverbeek, M., Duez, P., 2014. Inhibition of myeloperoxidase activity by the alkaloids of Peganum harmala L (Zygophyllaceae).J. Ethnopharmacol. 154, 361-369.

Cheng. X.M., Zhao, T., Yang, T., Wang, C.H., Bligh, S.WA, Wang, Z.T., 2010. HPLC fingerprints combined with principal component analysis, hierarchical cluster analysis and linear discriminant analysis for the classification and differentiation of Peganum sp. indigenous to China. Phytochem. Anal. 21, 279-289.

Chinese Pharmacopoeia Committee, 1998. Drug Standards of the Ministry of Public Health of the People's Republic of China (Uygur Pharmaceutical Section), p. 80.

Dorsch, W.. Wagner, H., 1991. New anti-asthmatic drugs from traditional medicine. Int. Arch Allergy. Appl. Immunol. 94, 262-265.

Duan, J.A., Che, C.T., Zhou, R.H., Zhao, S.X., Wang, M.S., 1998. Studies on the chemical constituents of Peganum multisectum Maxim II. Flavonoids and alkaloids from aerial part of plant. J. China Pharm. U. 29, 100-104.

Farouk, L, Laroubi, A., Aboufatima, R., Benharref, A., Chait, A., 2008. Evaluation of the analgesic effect of alkaloid extract of Peganum harmala L.: Possible mechanisms involved. J. Ethnopharmacol. 115, 449-454.

Ge, Y.B., Liu, J.Q., Su, D.F., 2009. In vivo evaluation of the anti-asthmatic, antitussive and expectorant activities of extracts and fractions from Elaeagnus pungens leaf. J. Ethnopharmacol. 126, 538-542.

Han, N., Chang, C.L., Wang, Y.C., Huang, T., Liu, Z.H., Yin, J., 2010. The in vivo expectorant and antitussive activity of extract and fractions from Reineckia carnea. J. Ethnopharmacol. 131, 220-223.

Hemmateenejad, B., Abbaspour, A., Maghami, H., Miri, R., Panjehshahin, M.R., 2006. Partial least squares-based multivariate spectral calibration method for simultaneous determination of beta-carboline derivatives in Peganum harmala seed extracts. Anal. Chim. Acta 575, 290-299.

Hider, R.C., Smart, L, Suleiman, M.S., 1981. The effect of harmaline and related ficarbolines on the acetylcholine-stimulated contractions of guinea-pig ileum. Eur. J. Pharmacol. 70, 429-436.

Irwing, R.S., Madison, J.M., 2000. The diagnosis and treatment of cough. New Engl. J. Med. 34, 1715-1721.

Jiangsu New Medical College, 1977. Encyclopedia of Chinese Materia Medica (Appendix). Shanghai People's Press, Shanghai, pp. 595-596.

Liu, L., Zhao, T., Cheng, X.M., Wang, C.H., Wang, Z.T., 2013. Characterization and determination of trace alkaloids in seeds extracts from Peganum harmala Linn using LC-ESI-MS and HPLC. Acta Chromatogr. 25, 221-240.

Liu, W., Cheng, X.M., Wang, Y.L, Li, S.P., Zheng, T.H., Gao, Y.Y., Wang, G.F., Qi, S.L., Wang, J.X., Ni, J.Y., Wang, Z.T., Wang, C.H., 2015a. In vivo evaluation of the antitussive, expectorant and bronchodilating effects of extract and fractions from aerial parts of Peganum harmala Linn. J. Ethnopharmacol. 162, 79-86.

Liu, W, Shi, X.Y., Yang, Y.D., Cheng, X.M., Liu, Q,, Han, H., Yang, B.H., He, C.Y., Wang, Y.L, Jiang, B.. Wang, Z.T., Wang, C.H., 2015b. In vitro and in vivo metabolism and inhibitory activities of vasicine, a potent acetylcholinesterase and butyrylcholinesterase inhibitor. PLoS ONE. 10, e0122366.

Newman, D.J., Cragg, G.M., 2007. Natural products as sources of new drugs over the last 25 years. J. Nat. Prod. 70, 461-477.

Nie, Z.G., Liang, C.Y., Gao, C.Y., Wang, S.Y., 2004. Effects of harmala alkaloids on the contraction of isolated guinea-pig tracheal smooth muscle in vitro. West China J. Pharm. Sci. 19, 266-268.

Perez, C.G., Zavala, M.A.S., Ventura, E.R., Perez, S.G., Ponce, H.M., 2008. Evaluation of anti-tussive activity of Chamaedorea tepejilote. J. Ethnopharmacol. 120, 138-140.

Plugar', V.N., Abdullaev, N.D., Rashkes, Ya.V., Yagudaev, M.R., Tulyaganov, N., 1983. Structure of the products of the metabolism of deoxypeganine and of deoxyvasicinone. Chem. Nat. Comp. 19, 720-727.

Rachana, S.B., Pant, M., Kumar, M.P., Saluja, S.. 2011. Review and future perspectives of using vasicine, and related compounds. Indo. Global J. Pharm. Sci. 1, 85-98.

Shang, J.H., Cai, X.H., Zhao, Y.L., Feng, T, Luo, X.D., 2010. Pharmacological evaluation of Alstonia scholaris: Anti-tussive, anti-asthmatic and expectorant activities. J. Ethnopharmacol. 129, 293-298.

Sharma, S.C., Siddiqi, M.A., Zutshi, U., Atal, C.K, 1983.The in vivo metabolism of vasicinea potent uterotonic. Indian Drugs 20, 431-434.

Wang, C.H., Liu. J., Zheng, L.M., Lin, Y.M., Zou, X.G., Chen, M., Sun, D.J., 2002. Analysis of harmine and harmaline of Peganum harmala in different parts and different localities. Chin. Pharm. J. 37, 211-215.

Wang, D.D., Wang, S., Chen, X., Xu, X.L., Zhu, J.Y., Nie, LH., Long, X., 2012. Antitussive, expectorant and anti-inflammatory activities of four alkaloids isolated from Bulbus of Fritillariawabuensis. J. Ethnopharmacol. 139, 189-193.

Wen, F.F., Cheng, X.M., Liu, W., Xuan, M., Zhang, L., Zhao, X., Shan, M., Li, Y., Teng, L, Wang, Z.T., Wang, C.H., 2014. Chemical fingerprint and simultaneous determination of alkaloids and flavonoids in aerial parts of genus Peganum indigenous to China based on HPLC-UV: Application of analysis on secondary metabolites accumulation. Biomed. Chromatogr. 28, 1763-1773.

Xu, S.Y., Bian, R.L., Chen, X., 1991. Pharmacological Experiment Methodology. People's Medical Publishing House. Beijing, China, p, 1167,

Zhang, J.L, Wang, H., Chen, C., Pi, H.F., Ruan, H.L, Zhang, P., Wu, J.Z., 2009. Addictive evaluation of cholic acid-verticinone ester, a potential cough therapeutic agent with agonist action of opioid receptor. Acta Pharmacol. Sin. 30, 559-566.

Zheng, X.Y., Zhang, Z.J., Chou, GX., Wu, T., Cheng, X.M., Wang, C.H., Wang, Z.T., 2009. Acetylcholinesterase inhibitive activity-guided isolation of two new alkaloids from seeds of Peganum nigellastrum Bunge by an in vitro TLC- bioautographic assay. Arch. Pharm. Res. 32, 1245-1251.

Wei Liua, Yongli Wang (a,b), Dan-dan He (a), Shu-ping Li (a), Yu-dan Zhu (a), Bo Jiang (a), Xue-mei Cheng (a,b), Zheng-tao Wang (a,b), Chang-hong Wang (a,b), *

(a) Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, 1200 Cailun Rood, Shanghai 201203, China

(b) Shanghai R&D Centre for Standardization of Chinese Medicines, 199 Guoshoujing Road, Shanghai 201210, China

Abbreviations: APP, aerial parts of Peganum harmala L; VAS, vasicine; DVAS, deoxyvasicine; VAO, vasicinone; CMC-Na, carboxymethylcellulose-sodium; TLC, thin layer chromatography; RF, rate of flow; HPLC, high performance liquid chromatography.

* Corresponding author at: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, 1200 Cailun Rood, Shanghai 201203, China. Tel.: 086 021 51322511; fax: 086 021 51322519.

E-mail address: wchcxm@hotmail.com (C.-h. Wang).
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Author:Liu, Wei; Wang, Yongli; He, Dan-dan; Li, Shu-ping; Zhu, Yu-dan; Jiang, Bo; Cheng, Xue-mei; Wang, Zhe
Publication:Phytomedicine: International Journal of Phytotherapy & Phytopharmacology
Article Type:Report
Geographic Code:9CHIN
Date:Nov 15, 2015
Words:5132
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