The Open Bioactive Compounds Journal




ISSN: 1874-8473 ― Volume 7, 2019

Inhibitory Effects of Two Ferulates from Angelica Sinensis on Platelet Aggregation and Oxytocin-induced Uterine Contraction



Y. Yu1, B. Q. Lin1, L. Yu2, Y. Q. Hua2, J. A. Duan2, S. P. Li1, 2, *
1 Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China
2 Jiangsu Key Laboratory for TCM Formulae Research, Nanjing University of Chinese Medicine, Nanjing, China

Abstract

Ferulic acid (FA) is widely considered as a biologically active component in Angelica sinensis, and used as one of the marker compounds for the quality control of Angelica sinensis. However, in A. sinensis, FA mainly exists as its ester, coniferyl ferulate (CF). CF is unstable and readily hydrolyzed into FA during conventional extraction. Herein, their antiplatelet aggregation activities and relaxant effects on oxytocin-induced mouse uterine muscle contraction were investigated and compared. The results showed that FA inhibited arachidonic acid (AA), adenosine diphosphate (ADP) and thrombin (THR)-induced platelet aggregation with IC50 values of 974.8 ± 97.5, 737.9 ± 40.2 and 244.6 ± 25.6 μg/ml, respectively. The potency of CF is much higher than that of FA, and the IC50 values for AA, ADP and THR were 7.1 ± 0.3, 276.4 ± 53.4 and 77.5 ± 23.1 μg/ml, respectively. IC50 of FA was 23.8 ± 6.2 μg/ml for oxytocin-induced uterine contraction in vitro. CF could only be tested at low concentration and its IC50 could not be calculated thereafter because of its strong hydrophobic property. So CF has more potent antiplatelet aggregation activity, while FA has stronger inhibitory effect on oxytocin-induced uterine contraction in vitro

Keywords: Angelica sinensis, coniferyl ferulate, ferulic acid, antiplatelet aggregation, oxytocin-induced uterine contraction.


Article Information


Identifiers and Pagination:

Year: 2009
Volume: 2
First Page: 43
Last Page: 46
Publisher Id: TOBCJ-2-43
DOI: 10.2174/1874847300902010043

Article History:

Received Date: 14/2/2009
Revision Received Date: 30/7/2009
Acceptance Date: 25/10/2009
Electronic publication date: 23/12/2009
Collection year: 2009

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* Address correspondence to this author at the Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China; Tel: +853-8397 4692; Fax: +853-2884 1358; E-mail: lishaoping@hotmail.com





INTRODUCTION

Angelica sinensis, known as Danggui in China, has been used for thousand years as traditional Chinese, Korean, and Japanese medicine. Nearly 19% of the traditional Chinese medicinal preparations recorded in Chinese Pharmacopeia (2005 edition) contain A. sinensis. A. sinensis can enrich blood, activate blood circulation, regulate menstruation, relieve pain, and relax bowels, and is used for the treatment of anemia with dizziness and palpitation, amenorrhea, dysmenorrhea, constipation, rheumatic arthralgia, traumatic injuries, carbuncles, boils and sores [1The State Pharmacopoeia Commission of the People’s Republic of China Pharmacopoeia of the People s Republic of China 2005; 1: 89.]. Modern studies have shown that A. sinensis has multiple pharmacological activities [2Xia Q, Zhang P, Li SP, Wang YT. The pharmacological progress of the study on Angelica sinensis Lishizhen Med Mater Med Res 2004; 15(3): 164-6.], including anti-inflammatory [3Xie CH, Zhang MS, Zhou YF, et al. Chinese medicine Angelica sinensis suppresses radiation-induced expression of TNF-a and TGF-ß1 in mice Oncol Rep 2006; 15(6 ): 1429-36.], antioxidant [4Wu SJ, Ng LT, Lin CC. Antioxidant activities of some common ingredients of traditional Chinese medicine, Angelica sinensis, Lycium barbarum and Poria cocos Phytother Res 2004; 18(12): 1008-12.
[http://dx.doi.org/10.1002/ptr.1617] [PMID: 15742346]
], immunostimulative [5Yang TH, Jia M, Meng J, Wu H, Mei Q. Immunomodulatory activity of polysaccharide isolated from Angelica sinensis Int J Biol Macromol 2006; 39(4-5): 179-84.
[http://dx.doi.org/10.1016/j.ijbiomac.2006.02.013] [PMID: 16839602]
], antiplatelet aggregation [6Dong WG, Liu SP, Zhu HH, Luo HS, Yu JP. Abnormal function of platelets and role of Angelica sinensis in patients with ulcerative colitis World J Gastroenterol 2004; 10(4 ): 606-9.
[PMID: 14966927]
], antitumor [7Cheng YL, Chang WL, Lee SC, et al. Acetone extract of Angelica sinensis inhibits proliferation of human cancer cells via inducing cell cycle arrest and apoptosis Life Sci 2004; 75(13): 1579-94.
[http://dx.doi.org/10.1016/j.lfs.2004.03.009] [PMID: 15261763]
, 8Tsai NM, Lin SZ, Lee CC, et al. The antitumor effects of Angelica sinensis on malignant brain tumors in vitro and in vivo Clin Cancer Res 2005; 11(9): 3475-84.
[http://dx.doi.org/10.1158/1078-0432.CCR-04-1827] [PMID: 15867250]
] and estrogenic [9Circosta C, Pasquale RD, Palumbo DR, Samperi S, Occhiuto F. Estrogenic activity of standardized extract of Angelica sinensis Phytother Res 2006; 20(8): 665-9.
[http://dx.doi.org/10.1002/ptr.1928] [PMID: 16691630]
] activities. Ferulic acid (FA) is usually considered as a biologically active component, and has been used as one of the marker compounds for the quality control of A. sinensis [1The State Pharmacopoeia Commission of the People’s Republic of China Pharmacopoeia of the People s Republic of China 2005; 1: 89.]. Indeed, FA has antioxidant [10Thyagaraju B M. Muralidhara Ferulic Acid supplements abrogate oxidative impairments in liver and testis in the streptozotocin-diabetic rat Zoolog Sci 2008; 25(8): 854-60.
[http://dx.doi.org/10.2108/zsj.25.854] [PMID: 18795822]
], anti-inflammatory [11Cheng CY, Ho TY, Lee EJ, Su SY, Tang NY, Hsieh CL. Ferulic Acid reduces cerebral infarct through its antioxidative and anti-inflammatory effects following transient focal cerebral ischemia in rats Am J Chin Med 2008; 36(6 ): 1105-19.
[http://dx.doi.org/10.1142/S0192415X08006570] [PMID: 19051339]
], antitumor [12Alias LM, Manoharan S, Vellaichamy L, Balakrishnan S, Ramachandran CR. Protective effect of ferulic acid on 7 12-dimethylbenz[a]anthracene-induced skin carcinogenesis in Swiss albino mice Exp Toxicol Pathol 2009; 61(3): 205-14.], anti-diabetes [13Mandal S, Barik B, Mallick C, De D, Ghosh D. Therapeutic effect of ferulic acid an ethereal fraction of ethanolic extract of seed of Syzygium cumini against streptozotocin-induced diabetes in male rat Methods Find Exp Clin Pharmacol 2008; 30(2 ): 121-8.
[http://dx.doi.org/10.1358/mf.2008.30.2.1143090] [PMID: 18560627]
], antimicrobial [14Gardjeva PA, Dimitrova SZ, Kostadinov ID, et al. A study of chemical composition and antimicrobial activity of Bulgarian propolis Folia Med (Plovdiv) 2007; 49(3-4): 63-9.], anti-hypertension and anti-hyperlipidemia [15ArdiansyahOhsaki Y, Shirakawa H, Koseki T, Komai M. Novel effects of a single administration of ferulic acid on the regulation of blood pressure and the hepatic lipid metabolic profile in stroke-prone spontaneously hypertensive rats J Agric Food Chem 2008; 56(8 ): 2825-30.
[http://dx.doi.org/10.1021/jf072896y] [PMID: 18345632]
] activities, and protective effect on iron- and nicotine-induced toxicity [16Chao HM, Chen YH, Liu JH, et al. Iron-generated hydroxyl radicals kill retinal cells in vivo effect of ferulic acid Hum Exp Toxicol 2008; 27(4): 327-39., 17Adluri RS, Nagarajan D, Periyaswamy V, Venugopal PM. Dose-response effect of ferulic acid against nicotine-induced tissue damage and altered lipid levels in experimental rats a pathohistological evaluation Fundam Clin Pharmacol 2008; 22(5): 557-67.
[http://dx.doi.org/10.1111/j.1472-8206.2008.00622.x] [PMID: 18844727]
]. However, in A. sinensis, FA mainly exists as its ester, coniferyl ferulate (CF). CF is unstable and readily hydrolyzed into FA during conventional extraction [18Lu GH, Chan K, Leung K, Chan CL, Zhao ZZ, Jiang ZH. Assay of free ferulic acid and total ferulic acid for quality assessment of Angelica sinensis J Chromatogr A 2005; 1068(2 ): 209-19.
[http://dx.doi.org/10.1016/j.chroma.2005.01.082] [PMID: 15830926]
, 19Xie JJ, Lu J, Qian ZM, Yu Y, Duan JA, Li SP. Optimization and comparison of five methods for extraction of coniferyl ferulate from Angelica sinensis Molecules 2009; 14(1): 555-65.
[http://dx.doi.org/10.3390/molecules14010555] [PMID: 19169202]
] although CF also has antineoplastic [20Kong L, Yu Z, Bao Y, Su X, Zou H, Li X. Screening and analysis of an antineoplastic compound in Rhizoma Chuanxiong by means of in vitro metabolism and HPLC-MS Anal Bioanal Chem 2006; 386(2): 264-74.
[http://dx.doi.org/10.1007/s00216-006-0621-0] [PMID: 16868728]
], antibacterial [21Chou SC, Everngam MC, Sturtz G, Beck JJ. Antibacterial activity of components from Lomatium californicum Phytother Res 2006; 20(2): 153-6.
[http://dx.doi.org/10.1002/ptr.1828] [PMID: 16444670]
] and antioxidant [22Li SY, Yu Y, Li SP. Identification of antioxidants in essential oil of Radix Angelicae sinensis using HPLC coupled with DAD-MS and ABTS-based assay J Agric Food Chem 2007; 55(9): 3358-62.
[http://dx.doi.org/10.1021/jf070140t] [PMID: 17411069]
] effects. So it is interesting to investigate and compare their potency of pharmacological activities, which will help to improve clinical usesof A. sinensis.

In the present study, antiplatelet aggregation and uterus-regulating activities of FA and CF, two ferulates related to A. sinensis, were investigated and compared.

MATERIALS AND METHODS

Materials

Arachidonic acid (AA), adenosine diphosphate (ADP) and FA (Fig. 1A) were purchased from Sigma (St. Louis, MO, USA). Thrombin (THR) was the product of Dade Behring (Eschborn, Germany). Disposable cuvettes for antiplatelet aggregation assay were from SUCCESS Technology Development Co. Ltd (Beijing, China). Deionized water was prepared using a Millipore Milli Q-Plus system (Millipore, Billerica, MA, USA). All other chemicals not mentioned here were analytical grade from standard sources. CF (purity > 95.0% determined by HPLC, Fig. 1B) was separated and purified from essential oil of A. sinensis in our lab [23Lin LZ, He XG, Lian LZ, King W, Elliott J. Liquid chromatographic-electrospray mass spectrometric study of the phthalides of Angelica sinensis and chemical changes of Z-ligustilide J Chromatogr A 1998; 810(1-2 ): 71-9.
[http://dx.doi.org/10.1016/S0021-9673(98)00201-5]
]. The structure of CF was confirmed by its UV, MS, 1H-NMR and 13C-NMR data [19Xie JJ, Lu J, Qian ZM, Yu Y, Duan JA, Li SP. Optimization and comparison of five methods for extraction of coniferyl ferulate from Angelica sinensis Molecules 2009; 14(1): 555-65.
[http://dx.doi.org/10.3390/molecules14010555] [PMID: 19169202]
, 24Lu XH, Zhang JJ, Liang H, Zhao YY. Chemical constituents of Angelica sinensis J Chin Pharmaceut Sci 2004; 13(1): 1-3.].

Fig. (1)

Chemical structures of ferulic acid (FA) and coniferyl ferulate (CF).



Animals

The experiments were performed in accordance with the Animal Ethics Committee of Nanjing University of Chinese Medicine. Male New Zealand white rabbits (1.8-2.5 kg) and non-pregnant sexually mature female Kunming mice (6-7 weeks, 18-22 g) were obtained from Experimental Animal Center, Nanjing University of Chinese Medicine. All animals were maintained on a pellet diet and water ad libitum and kept under the laboratory condition of light/dark cycle 12/12 hours.

Antiplatelet Aggregation Assay in vitro

Rabbit platelets were used for antiplatelet aggregation assays. Blood from the rabbit carotid artery was collected in plastic tubes and anticoagulated with 3.2% sodium citrate solution (9:1, v/v). The blood sample was centrifuged at 100 × g for 10 min, platelet rich plasma was obtained. Then the precipitate was centrifuged at 1,925 × g for another 10 min to obtain platelet poor plasma. The final count of platelets in platelet rich plasma was adjusted to 7×109 cells/ml with platelet poor plasma.

FA and CF were dissolved in dimethyl sulfoxide. Stock solutions of AA, ADP and THR were prepared with 1% sodium bicarbonate solution, phosphate buffer solution and deionized water, respectively.

Antiplatelet aggregation assays were performed by turbidimetric method [25Born GVR. Aggregation of blood platelets by adenosine diphosphate and its reversal Nature 1962; 194(4832): 927-9.
[http://dx.doi.org/10.1038/194927b0] [PMID: 13871375]
] on a SC-2000 aggregometer (SUCCESS Technology Development Co. Ltd, Beijing). The test samples were pre-incubated with platelets for 5 min at 37 (C. Then the platelet aggregation was induced by addition of AA, ADP or THR solution with final concentration of 330 μM, 15 μM and 0.3 IU, respectively. All tests were performed within 3 h after the collection of blood. Corresponding solvents were used as blank controls for the corresponding test. The antiplatelet aggregation potency is expressed as inhibition (%) which was calculated as follows:

Inhibition% = (A - B) / A × 100%

where A and B were the absorbance values of corresponding blank controls and test samples, respectively.

Oxytocin-induced Uterine Contraction Assay in vitro

Oxytocin-induced female mice uterine contraction assay was tested in vitro [26Chao J, Buse J, Shimamoto K, Margolius HS. Kallikrein-induced uterine contraction independent of kinin formation Proc Natl Acad Sci USA 1981; 78(10 ): 6154-7.
[http://dx.doi.org/10.1073/pnas.78.10.6154] [PMID: 6947218] [PMCID: PMC348996]
]. In brief, synchronistically estrus mice were pretreated with estradiol benzoate (5 mg/kg, s.c.) 24 h prior to the study. On the third day, the mice were sacrificed by cervical dislocation and the uteri were isolated. The whole uterus was taken as one sample. The cervical end was tied to perspex holder, and the two ovarian ends were put together as another end tied to an isometric force transducer. A resting tension of 1 g was applied for superfusion with oxygenated Krebs (95% O2, 5% CO2, pH 7.3) at 37 (C. Equilibration period was not less than 45 min. After establishing a steady basal tone, oxytocin (5 U/ml) was added to baths. Once the contraction reached a plateau, FA and CF of cumulative concentrations were added to organ bath with an interval of about 10 min. Dimethyl sulfoxide (3‰) was taken as vehicle control. Contractions were recorded by PowerLab/8s data recording system (AD Instruments, Australia) which was linked to a mackintosh computer (Powermac 7200/120, Apple, USA) where Chart software (v. 4.2.2 AD Instruments, Australia) was used to display and measure the tension changes of tissues. Antioxytocin effects were expressed as a percentage of relaxation based on 5 U/ml oxytocin-induced plateau contraction.

Statistical Analysis

Data were expressed as the mean ± SD and presented as an average of three replicates. The IC50 (the concentration that providing 50% inhibition) values were calculated based on linear regression of the inhibitory capacities to the concentrations or the logistics of concentration.

RESULTS AND DISCUSSION

The Effects of FA and CF on Platelet Aggregation in vitro

Both FA and CF concentration-dependently inhibited AA, ADP and THR-induced platelet aggregations. As shown in Table 1, FA inhibited platelet aggregation induced by AA, ADP and THR with IC50 values of 974.8 ± 97.5, 737.9 ± 40.2 and 244.6 ± 25.6 μg/ml, respectively. The potency of CF is much higher than that of FA, and the IC50 values for AA, ADP and THR were 7.1 ± 0.3, 276.4 ± 53.4 and 77.5 ± 23.1 μg/ml, respectively. The results of FA agreed with Ou’s report which also showed that FA had antiplatelet aggregation effect [27Ou S, Kwok KC. Ferulic acid: pharmaceutical functions, preparation and applications in food J Sci Food Agric 2004; 84(11 ): 1261-9.
[http://dx.doi.org/10.1002/jsfa.1873]
]. The results accounted for the antiplatelet aggregation mechanismof A. sinensis injection [6Dong WG, Liu SP, Zhu HH, Luo HS, Yu JP. Abnormal function of platelets and role of Angelica sinensis in patients with ulcerative colitis World J Gastroenterol 2004; 10(4 ): 606-9.
[PMID: 14966927]
] and activation blood circulation mechanism of A. sinensis [1The State Pharmacopoeia Commission of the People’s Republic of China Pharmacopoeia of the People s Republic of China 2005; 1: 89.]. CF had stronger effect than FA, but CF is unstable and readily hydrolyzed into FA during conventional extraction, which indicates that we should improve extraction method to reduce such hydrolysis when A. sinensis was mainly used to improve platelet aggregation.

Table 1

Inhibitory Effects of FA and CF on Rabbit Platelet Aggregation Induced by AA (330 µM), ADP (15 µM) and THR (0.3U/ml)In Vitro.




The Effects of FA and CF on Oxytocin-induced Uterine Contraction in vitro

Oxytocin, a nonapeptide hormone, induces uterine and mammary gland contractions. Both tissues express oxytocin receptors. The number of these receptors is increased by estrogen and decreased by progesterone [28Parker KL, Schimmer BP, Brunton LL, Lazo JS, Eds. Goodman & Gilman’s the Pharmacological Basis of Therapeutics In Pituitary Hormones and Their Hypothalamic Releasing Factors 2006; 1489-510.]. So the mice were pretreated with estradiol benzoate 24 h prior to the study to increase the oxytocin receptor numbers and thus increase the sensitivity of uterine to the stimulation of oxytocin in vitro.

The results showed that both FA and CF inhibited oxytocin-induced uterine contraction in a concentration-dependent manner, and FA had more potent inhibitory effect than CF (Fig. 2). Actually, the concentration-dependent response of CF only could be found when the concentration beyond 25 μg/ml according to Fig. (2), and the concentrations of CF below 25 μg/ml had no obvious inhibition on oxytocin-induced mice uterine contraction. IC50 of FA was 23.8 ± 6.2 μg/ml. Potent prostaglandins and potent leukotrienes play an important role in generating primary dysmenorrhea symptoms [29Harel Z. Dysmenorrhea in adolescents and young adults from pathophysiology to pharmacological treatments and management strategies Expert Opin Pharmacother 2008; 9(15): 2661-72.
[http://dx.doi.org/10.1517/14656566.9.15.2661] [PMID: 18803452]
], so the anti-inflammatory effect of A. sinensis may help to treat dysmenorrhea [3Xie CH, Zhang MS, Zhou YF, et al. Chinese medicine Angelica sinensis suppresses radiation-induced expression of TNF-a and TGF-ß1 in mice Oncol Rep 2006; 15(6 ): 1429-36.]. Moreover, in non-pregnant women, the oxytocin receptor density varies over the menstrual cycle and increases markedly at the onset of menstruation. So blocking the uterine oxytocin receptor can inhibit primary dysmenorrhoea [30Akerlund M. Vasopressin and oxytocin in normal reproduction and in the pathophysiology of preterm labour and primary dysmenorrhoea Development of receptor antagonists for therapeutic use in these conditions Rocz Akad Med Bialymst 2004; 49: 18-21.
[PMID: 15631309]
]. Therefore, the potent anti-spasm activity of FA on oxytocin-induced uterine contraction could also partly elucidate the anti-dysmenorrhea mechanism of A. sinensis. Since CF has strong hydrophobic property, it could only be tested at low concentration and its IC50 could not be calculated thereafter. The results suggest that FA is a good form when A. sinensis is used to inhibit the oxytocin-induced uterine contraction.

Fig. (2)

The inhibitory effects of FA and CF on oxytocininduced mice uterine muscle contraction in vitro. The data were expressed as mean ± SD of three replicates.*P<0.05 and **P<0.01 vs. vehicle control.



In conclusion, the pharmacological activities of two ferulates, FA and CF, had their own characters. CF has more potent antiplatelet aggregation activity, while FA has stronger inhibitory effect on oxytocin-induced uterine contraction. The results suggest that different extraction methods of A. sinensis are necessary according to its different treatment purposes.

ACKNOWLEDGEMENTS

The research was supported by grants from Jiangsu Key Laboratory for TCM Formulae Research, Nanjing University of Chinese Medicine (No.022021014003) and University of Macau (RG083/07-08S) to S.P. Li.

REFERENCES

[1] The State Pharmacopoeia Commission of the People’s Republic of China Pharmacopoeia of the People s Republic of China 2005; 1: 89.
[2] Xia Q, Zhang P, Li SP, Wang YT. The pharmacological progress of the study on Angelica sinensis Lishizhen Med Mater Med Res 2004; 15(3): 164-6.
[3] Xie CH, Zhang MS, Zhou YF, et al. Chinese medicine Angelica sinensis suppresses radiation-induced expression of TNF-a and TGF-ß1 in mice Oncol Rep 2006; 15(6 ): 1429-36.
[4] Wu SJ, Ng LT, Lin CC. Antioxidant activities of some common ingredients of traditional Chinese medicine, Angelica sinensis, Lycium barbarum and Poria cocos Phytother Res 2004; 18(12): 1008-12.
[http://dx.doi.org/10.1002/ptr.1617] [PMID: 15742346]
[5] Yang TH, Jia M, Meng J, Wu H, Mei Q. Immunomodulatory activity of polysaccharide isolated from Angelica sinensis Int J Biol Macromol 2006; 39(4-5): 179-84.
[http://dx.doi.org/10.1016/j.ijbiomac.2006.02.013] [PMID: 16839602]
[6] Dong WG, Liu SP, Zhu HH, Luo HS, Yu JP. Abnormal function of platelets and role of Angelica sinensis in patients with ulcerative colitis World J Gastroenterol 2004; 10(4 ): 606-9.
[PMID: 14966927]
[7] Cheng YL, Chang WL, Lee SC, et al. Acetone extract of Angelica sinensis inhibits proliferation of human cancer cells via inducing cell cycle arrest and apoptosis Life Sci 2004; 75(13): 1579-94.
[http://dx.doi.org/10.1016/j.lfs.2004.03.009] [PMID: 15261763]
[8] Tsai NM, Lin SZ, Lee CC, et al. The antitumor effects of Angelica sinensis on malignant brain tumors in vitro and in vivo Clin Cancer Res 2005; 11(9): 3475-84.
[http://dx.doi.org/10.1158/1078-0432.CCR-04-1827] [PMID: 15867250]
[9] Circosta C, Pasquale RD, Palumbo DR, Samperi S, Occhiuto F. Estrogenic activity of standardized extract of Angelica sinensis Phytother Res 2006; 20(8): 665-9.
[http://dx.doi.org/10.1002/ptr.1928] [PMID: 16691630]
[10] Thyagaraju B M. Muralidhara Ferulic Acid supplements abrogate oxidative impairments in liver and testis in the streptozotocin-diabetic rat Zoolog Sci 2008; 25(8): 854-60.
[http://dx.doi.org/10.2108/zsj.25.854] [PMID: 18795822]
[11] Cheng CY, Ho TY, Lee EJ, Su SY, Tang NY, Hsieh CL. Ferulic Acid reduces cerebral infarct through its antioxidative and anti-inflammatory effects following transient focal cerebral ischemia in rats Am J Chin Med 2008; 36(6 ): 1105-19.
[http://dx.doi.org/10.1142/S0192415X08006570] [PMID: 19051339]
[12] Alias LM, Manoharan S, Vellaichamy L, Balakrishnan S, Ramachandran CR. Protective effect of ferulic acid on 7 12-dimethylbenz[a]anthracene-induced skin carcinogenesis in Swiss albino mice Exp Toxicol Pathol 2009; 61(3): 205-14.
[13] Mandal S, Barik B, Mallick C, De D, Ghosh D. Therapeutic effect of ferulic acid an ethereal fraction of ethanolic extract of seed of Syzygium cumini against streptozotocin-induced diabetes in male rat Methods Find Exp Clin Pharmacol 2008; 30(2 ): 121-8.
[http://dx.doi.org/10.1358/mf.2008.30.2.1143090] [PMID: 18560627]
[14] Gardjeva PA, Dimitrova SZ, Kostadinov ID, et al. A study of chemical composition and antimicrobial activity of Bulgarian propolis Folia Med (Plovdiv) 2007; 49(3-4): 63-9.
[15] ArdiansyahOhsaki Y, Shirakawa H, Koseki T, Komai M. Novel effects of a single administration of ferulic acid on the regulation of blood pressure and the hepatic lipid metabolic profile in stroke-prone spontaneously hypertensive rats J Agric Food Chem 2008; 56(8 ): 2825-30.
[http://dx.doi.org/10.1021/jf072896y] [PMID: 18345632]
[16] Chao HM, Chen YH, Liu JH, et al. Iron-generated hydroxyl radicals kill retinal cells in vivo effect of ferulic acid Hum Exp Toxicol 2008; 27(4): 327-39.
[17] Adluri RS, Nagarajan D, Periyaswamy V, Venugopal PM. Dose-response effect of ferulic acid against nicotine-induced tissue damage and altered lipid levels in experimental rats a pathohistological evaluation Fundam Clin Pharmacol 2008; 22(5): 557-67.
[http://dx.doi.org/10.1111/j.1472-8206.2008.00622.x] [PMID: 18844727]
[18] Lu GH, Chan K, Leung K, Chan CL, Zhao ZZ, Jiang ZH. Assay of free ferulic acid and total ferulic acid for quality assessment of Angelica sinensis J Chromatogr A 2005; 1068(2 ): 209-19.
[http://dx.doi.org/10.1016/j.chroma.2005.01.082] [PMID: 15830926]
[19] Xie JJ, Lu J, Qian ZM, Yu Y, Duan JA, Li SP. Optimization and comparison of five methods for extraction of coniferyl ferulate from Angelica sinensis Molecules 2009; 14(1): 555-65.
[http://dx.doi.org/10.3390/molecules14010555] [PMID: 19169202]
[20] Kong L, Yu Z, Bao Y, Su X, Zou H, Li X. Screening and analysis of an antineoplastic compound in Rhizoma Chuanxiong by means of in vitro metabolism and HPLC-MS Anal Bioanal Chem 2006; 386(2): 264-74.
[http://dx.doi.org/10.1007/s00216-006-0621-0] [PMID: 16868728]
[21] Chou SC, Everngam MC, Sturtz G, Beck JJ. Antibacterial activity of components from Lomatium californicum Phytother Res 2006; 20(2): 153-6.
[http://dx.doi.org/10.1002/ptr.1828] [PMID: 16444670]
[22] Li SY, Yu Y, Li SP. Identification of antioxidants in essential oil of Radix Angelicae sinensis using HPLC coupled with DAD-MS and ABTS-based assay J Agric Food Chem 2007; 55(9): 3358-62.
[http://dx.doi.org/10.1021/jf070140t] [PMID: 17411069]
[23] Lin LZ, He XG, Lian LZ, King W, Elliott J. Liquid chromatographic-electrospray mass spectrometric study of the phthalides of Angelica sinensis and chemical changes of Z-ligustilide J Chromatogr A 1998; 810(1-2 ): 71-9.
[http://dx.doi.org/10.1016/S0021-9673(98)00201-5]
[24] Lu XH, Zhang JJ, Liang H, Zhao YY. Chemical constituents of Angelica sinensis J Chin Pharmaceut Sci 2004; 13(1): 1-3.
[25] Born GVR. Aggregation of blood platelets by adenosine diphosphate and its reversal Nature 1962; 194(4832): 927-9.
[http://dx.doi.org/10.1038/194927b0] [PMID: 13871375]
[26] Chao J, Buse J, Shimamoto K, Margolius HS. Kallikrein-induced uterine contraction independent of kinin formation Proc Natl Acad Sci USA 1981; 78(10 ): 6154-7.
[http://dx.doi.org/10.1073/pnas.78.10.6154] [PMID: 6947218] [PMCID: PMC348996]
[27] Ou S, Kwok KC. Ferulic acid: pharmaceutical functions, preparation and applications in food J Sci Food Agric 2004; 84(11 ): 1261-9.
[http://dx.doi.org/10.1002/jsfa.1873]
[28] Parker KL, Schimmer BP, Brunton LL, Lazo JS, Eds. Goodman & Gilman’s the Pharmacological Basis of Therapeutics In Pituitary Hormones and Their Hypothalamic Releasing Factors 2006; 1489-510.
[29] Harel Z. Dysmenorrhea in adolescents and young adults from pathophysiology to pharmacological treatments and management strategies Expert Opin Pharmacother 2008; 9(15): 2661-72.
[http://dx.doi.org/10.1517/14656566.9.15.2661] [PMID: 18803452]
[30] Akerlund M. Vasopressin and oxytocin in normal reproduction and in the pathophysiology of preterm labour and primary dysmenorrhoea Development of receptor antagonists for therapeutic use in these conditions Rocz Akad Med Bialymst 2004; 49: 18-21.
[PMID: 15631309]

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Department of Pharmacy, World University of Bangladesh, Bangladesh


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