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10meditineprescription"hemorrhoidslotion"to washandShengjiyuhong ointmentgauzetochange dressing.
Results and discussion:
30 patients healed completely.Pathologydiagnosis"foreign body granuloma".The healing phase: 26~45days.Patients were followed up for 5 months~4years without recurrence.
2.1.Pathogenesis:In 1830 HerbertMayo firstdescribed this disease.The etiology of this diseaseremains controversial.Congenitalpilonidal sinusis due toincomplete separation between the backofneuroectodermaland skinectoderm,which easily complicated withbacterial meningitis,skinabscess,epidural andsubdural abscess[2] ; howere,acquiredtheory is that pilonidal sinusisdue to a hiptwistand friction in thewalk,hairbetweengluteal cleftstab intonearby skin.Karydakis[3] believes the cause of three elements: loose hair; cause hair into the suction; skin injury.
2.2:Diagnosis:The diseaseoccurs in young adults,a high prevalence ofwhite,and the disease is rare in domestic,higher misdiagnosis and recurrence rate.The disease should beidentifiedbetween perianalabscess,anal fistula,infectionof presacralteratoma,hidradenitis
suppurativa,andfuruncle,carbuncle,granuloma,lymphadenitis.The affected partcanbe seenthe irregularholes inthemidlineskin,the surrounding skinis usuallyseenswollen,some canbe seenhair.The probe canbeinto3~4cm,the woundcanbe dischargedthinsmellyliquid [4].A significant feature is that there ishairinsinus,butreportedpositive rate ofpilonidal sinushair isabout 40%~ 50%[5].
2.3:Treatment:the method of clinicaltreatment is dividedinto two kinds:operationtherapyand nonoperationtherapy.Nonoperationtherapyinclude sclerotherapy,Chinesesupportline and thepad pressuretherapy.At present,there are many methodsforoperation,such as one stage resection andsuture in the treatment,excisionwoundopen surgery,twosuture ofincision and drainage,spindleflapsuture,marsupialization,asymmetricresectionintradermalsuture,excisionwoundst amp graftingtreatment.
2.4Conclusion: the combination ofour hospital in 6monthstotreat 30 patients,the authors believe that the key tothe treatment of this diseasehas two,oneneeds tocompleteremoval of lesions,lesions ofthe residual isrecurrence.Second,postoperativedrainage isessentialto treat the disease,30patients were followed up for 1years,no recurrence.
References
[1]Li Chunyu, Zhang Yousheng. Practical anus operation (M) science. Shenyang: Liaoning science and Technology Press, 2005:258-262.
[2] Li Yuanyang, Shao Tong, Dong Xiaohong, et al. Occipital pilonidal sinus with cerebellar pilonidal sinus cyst [J]. Chinese Journal of surgery, 2006, 44 (2): 144
[3] Akinci OF, Coskun A, Uzunk y A. Simple and effective surgical treatment of pilonidal sinus: asymmetric excision and primary closure using suction drain and subcuticulor skin closure[J].Dis Co-Lon Rectum, 2000, 43 (5): 701-706.
[4] Wang Hong, Deng crane, Ming Shi, Journal of Tianjin University of Traditional Chinese Medicine, 2008:312-332
Bioactive constituents from the seeds of Pharbitis nil
Yanping SUN, Qiuhong WANG,Yanxin LIU, Haixue KUANG*
Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine,
Harbin, China.
Abstracts: Pharbitidis Semen, theseeds of Pharbitis nil Choisy, with the main bioactive constituentsresin glycosides, has been used as a purgative drug in folkloricmedicine. With the deepening of the study, the medicinal value of Pharbitidis Semen is gradually developedshowing a
good application prospect. In this paper, by reviewing the domestic and foreign research results, bioactive constituents and the medicinal value of the seeds of Pharbitis nilwere summarized.
Key words: bioactive constituents; seeds of Pharbitis nil; review
Pharbitidis Semen, the seeds of Pharbitis nil (PNS), comes from the pharbitis (also known as the morning glory), an annual climbing herb found throughout Southeast Asia that many people use as an ornamental plant. PNS, with two different kinds of seeds skin color of which is ash black or yellowish white, have been traditionally used asa purgative drug in Korea, China, and Japan.In traditional Chinese medicine (TCM), PNS has been used as a folk medicine for its analgesic effects against abdominal pain and for the treatment of a variety of digestive problems. In addition, PNSwas reported to exhibit anti-tumor activity, inducing apoptosis in AGC gastric cancer cells. PNS is also reported to produce anti-fungal peptides[1-3].
In recent years, PNShas been carry out in-depth research in many aspects, especially for its various phytochemical compounds, such as resin glycosides[4], phenolic acids[5'6], diterpenoids[7], triterpenoid saponins[8] and hevein homologous peptides[9], therefore this review reports on the main bioactive constituents and their biological characteristics, to provide a theoretical basis for further research of PNS.
1. Materials and methods
Literature survey was performed via electronic search (Pubmed®,SciFinder®, Google Scholar and Web of Science) on papers and patents and by systematic research in literature on chemical components and pharmacological activities of PNSat various university libraries.
2. Results and discussion
2.1Resin glycosides and their bioactivities
It is well known that a characteristic group of complex glycosides, so-called resin glycosides, is widely distributed in the Convolvulaceae plants as the constituents of their resinous purgative principles.
A preliminary investigation on this resin glycoside was made by some investigators in the 19th century and systematic examinations were carried out. And in 1990, alkaline hydrolysis of the ether-insoluble resin glycoside ("convolvulin") fraction, pharbitin, of PNS provided three organic acids, S-2-methylbutyric acid, (2^,3^)-nilic acid and tiglic acid, and a new glycosidic acid named pharbitic acid B along with the known compounds pharbitic acids C and D (Fig. 1).
Jingshu Xu[10]reported that the main ingredients pharbitins encounter bile and intestinal fluid in the intestinal and then they break down the water soluble constituent aglycone like jalapin, with a strong purgative effect, which can act on the central nervous system. So in the long-term or a large amount of use, pharbitins will cause severe irritation of the gastrointestinal tract and neurological symptoms.
2.2 Phenolic acids and their bioactivities
Phenolic acids occur naturally in plants and are their main polyphenols. In the plants, they act as signaling molecules and agents of defense. Since the acids are compounds of phenols, they are more commonly referred to as phenolic compounds.
Kim et al[5]isolated eight phenolic acids namely compounds 1-8 from the ethanol extract of PNS (Fig. 2). They were identified as (E)-ethyl caffeate (1), (E)-p-ethyl coumarate (2), (E)-ferulic acid (3), (E)-p-coumaric acid (4), (E)-caffeic acid (5), 3,4-dihydroxybenzaldehyde (6), (E)-ethyl ferulate 4-0-/9-D-glucopyranoside (7), and osmanthuside J (8). Additionally, Kimet al[6]also isolated two new phenolic amides identified as pharnilatin A (9) and pharnilatin B (10) (Fig. 2).
Among them, compounds 1 and2exhibited significant cytotoxicity against human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) with Rvalues ranging from 8.07 to 28.30 ^M. In addition, compounds 1 and2 potently inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells, a microglia cells with IC50 values ranging from 14.7 to 19.9^M.Compounds 9and 10also exhibited cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 human tumor cells. However, noneof the compounds inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated microglia cells.
14 12
14
12
\
3S COOH
2 Pharbitic acid C
H?O^o O
12C b
HO—^^O
HO^^^-V
O
Glc'
HO
Rha''
hoo
HO
OH
Fig. 1. Resin glycosides
O
R1
1: R1=OH, R2=ethyl 2: R^H, R2=ethyl 3: R1=OCH3, R2=H 4: R^H, R2=H 5: R1=OH, R2=H
OCH3
O o
HO
OH Qui
OH
Rha'
3 Pharbitic acid D
O
HO
H
GlcO
OH 6
O
Wbo^^O ^ - ho^^H
HO OH
OCH3 7
OH
O
Fig. 2. Phenolic acids
HO nh2
r
NH OH
O
2
8
2
2.3 Diterpenes and their bioactivities
Diterpene, a type of terpene, is an organic compound composed of four isoprene units and has the molecular formula C20H32. They derive from geranylgeranyl pyrophosphate. Diterpenes form the basis for biologically important compounds such as retinol, retinal, and phytol. They are known to be antimicrobial and antiinflammatory.
Kim et al[7]isolateda further six new ent-kaurane diterpene glycosides, pharbosidesA-F (1-6), a new ent-gibbane diterpene glycoside, pharboside G(7), and three known ent-kaurane diterpenoids [7/5,16/5,17-Trihydroxy-ent-kauran-6a,19-olide (8), 6/5,7/5,16a,17-Tetrahydroxy-ent-kauranoic acid (9), and 6/9,7/9,16/9,17-Tetrahydroxy-ent-kauranoic acid (10)] from the EtOAc-soluble and BuOH-soluble fractions of the ethanolic extract of PNS (Fig. 3).The isolatedcompounds were evaluated for their cytotoxic activities against four human cancer cell lines.
O^ORi
Ri R2
1 Glc ¡AOH
1a H ¡AOH
2 Glc ¡Aoh
2a H ¡Aoh
O OR O
7
7a
R
Glc H
OR3
or2
O
O
O
8
OR3
or2
Ri R2 R3 Ri R2 R3
3 CH3 Glc H 4 Glc H H
3a H H H 4a H H H
6 H Glc H 5 H H Glc
6a H H H 5a H H H
9 H H H 10 H H H
Fig. 3. Diterpenes
2.4 Triterpenoid saponins
Triterpenoid saponins are triterpenes which belong to the group of saponin compounds. Triterpenes belong to a large group of compounds arranged in a four or five ring configuration of 30 carbons with several oxygens attached.
Jung et al[8]isolatedtwo new oleanene-type triterpene glycosides, pharbitosidesA (1) and B (2), from PNS (Fig. 4). The structure of pharbitoside A (1) was elucidated to be queretaroic acid 3-O-a-L-rhamnopyra-nosyl-(1^2)-O-/9-D-glucopyranosyl-(1^2)-/9-D-glucopyranoside (1). Pharbitoside B (2) is a 21a-hydroxyoleanolicacid saponin carrying the same sugar moiety as that of pharbitoside A (1).
2.5 Hevein homologous peptides
Koo et al[9]purified and obtained two antifungal peptides (Pn-AMP1 and Pn-AMP2) to homogeneity from PNS. Theamino acid sequences of Pn-AMP1(41 amino acid residues) and Pn-AMP2(40 amino
acid residues) were identical exceptthat Pn-AMP1 has an additional serine residue at the carboxyl-terminus (Fig. 5).
Fig. 4. Triterpenoid saponins
Pn-AMP1<QQCGRQASGRLCGNRLCCSQWGYCGSTASYCGAGCQSQCRS Pn-AMP2<QQCGRQASGRLCGNRLCCSQWGYCGSTASYCGAGCQSQCR
Fig. 5. Amino acid sequences of the Pn-AMP1 and 2
Pn-AMPs exhibited potent antifungal activity against both chitin-containing and non-chitin-containing fungi in the cell wall. Concentrations required for 50% inhibition of fungal growth were ranged from 3 to 26 ^g/ml for Pn-AMP1 and from 0.6 to 75^g/ml for Pn-AMP2. The Pn-AMPs penetrated very rapidly into fungal hyphae and localized at septum and hyphal tips of fungi, which caused burst of hyphal tips. 3. Conclusions
There are multiple components in the crude extract of PNS. With the development of the extraction, separation, analysis methods, more effect of PNS will also be found with broad clinical application prospects. References
[1] Lee T.H., Choi J.J., Kim D.H., Choi S., Lee K.R., Son M., Jin M.Gastroprokinetic effects of DA-9701, a new prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber. Phytomedicine. -2008 Oct.-15(10).-P.836-843
[2] Ko S.G., Koh S.H., Jun C.Y., Nam C.G., Bae H.S., Shin M.K.Induction of apoptosis by Saussurea lappa and Pharbitis nil on AGS gastric cancer cells.Biol. Pharm. Bull. -2004 Oct.-27(10).-P.1604-1610
[3] Koo J.C., Lee S.Y., Chun H.J., Cheong Y.H., Choi J.S., KawabataS., Miyagi M., Tsunasawa S., Ha K.S., Bae D.W., Han C.D., Lee B.L., Cho M.J., Biochim. Biophys. Acta. -1998 Jan.-1382(1).-P.80-90
[4] Kawasaki T., Okabe H., Nakatsuka I.Studies on resin glycosides.ChemPharm Bull. -1971. -19.-P.1114-1149
[5] Kim K.H., Choi S.U., Son M.W., Lee K.R. Two New Phenolic Amides from the Seeds of Pharbitis nil. Chem. Pharm. Bull. -2010 Nov. -58(11). -P.1532-1535
[6] Kim K.H., Ha, S.K., Choi, S.U., Kim, S.Y., Lee, K.R. Bioactive Phenolic Constituents from the Seeds of Pharbitis nil. Chem. Pharm. Bull. -2011 Nov. -59(1).-P.1425-1429
[7] Kim K.H., Choi S.U., Lee K.R. Diterpene Glycosides from the Seeds of Pharbitis nil. J. Nat. Prod. -2009Feb.-72(6). -P 1121-1127
[8] Jung D.Y., Ha H., Lee H.Y., Kim C., Lee J.H., Bae K.H., Kim J.S., Kang S.S. Triterpenoid Saponins from the Seeds of Pharbitis nil. Chem. Pharm. Bull. -2008 Feb. -56(2). - P.203-206
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[9] Koo J.C., Lee S.Y., Chun H.J., Cheong Y.H., Choi J.S., Kawabata S., Miyagi M., Tsunasawa S., Ha K.S., Bae D.W., Han C.D., Lee B.L., Cho M.J. Two hevein homologs isolated from the seed of Pharbitis nil L. exhibit potent antifungal activity. Biochim Biophys Acta. -1998 Jan. -1382(1). -P.80-90
[10] Xu J.S. One case of Pharbitidis Semen poisoning. China's basic medical. -1994. -4(4). -P 108
Identification of the metabolites of Baicalin in rat urine by UPLC/ESI-TOF/MS coupled with MetaboLynx XS automated data analysis
Na Wanga, Fang Lua, Xuzhao Lia, Wanru Donga, Na Zhang a, Changfeng Liu a* Shumin Liua'b*
a Traditional Chinese medicine toxicology laboratory, Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, He Ping Road 24, Harbin 150040, China. b The center of GLP, Heilongjiang University of Chinese Medicine, He Ping Road 24, Harbin 150040, China.
Abstracts:To illustrate the main biotransformation pathways of Baicalin in vivo, we elucidated the metabolic profile of Baicalin in rat's urine. The urine was collected from each animal within 12 h after administrating orally Baicalin and distilled water (100mg/kg), and analyzed by ultra-performance liquid chromatography/electrospray ionization time-of-flight mass spectrometry (UPLC/ESI-TOF-MS) at the positive ion mode scanning coupled with MetaboLynx XS (version4.1) automated data analysis method. A total of 26 metabolites were detected, 13 of which were identified. A fairly comprehensive metabolic pathway was proposed for Baicalin include dehydroxylation, methylation, hydroxylation and glucuronidation after deglycosylation. These results are important for understanding the material basis and clinical mechanism of Baicalin for drug discovery, design and clinical application.
Keywords: Baicalin; metabolites; UPLC/ESI-TOF/MS; MetaboLynx XS
Drug metabolism (biotransformation) can contribute significantly to the overall therapeutic and adverse effects of drugs. As part of any drug discovery activity, it is important to analyze the metabolic profile of the parent drug.Baicalin (Fig.1), formulated as 7-D-glucuronic acid-5,6-dihydroxy-flavone, is a major bioactive constituent of Scutellariae Radix (root of Scutellaria Baicalensis Georgi) which has been known to have a multitude of pharmacological properties, such
12 2 3 4
as neuroprotective1, anti-diogenic2, anti-inflammatory2 , anticancer 3anti-bacterial, antioxidative4, antiviral5 and anti-HIV 6, et al. The metabolism of Baicalin has been preliminarily investigated. However, only a fewmetabolites including BBaicalein, oroxylin A, and their glucuronides were identified . Thus, those works only partly understood the metabolic performance of Baicalin.Herein, ultra-performance liquid chromatography/electrospray ionization time-of-flight mass spectrometry (UPLC/ESI-TOF/MS) followed by multiple mass defect filtering was applied to analyze the common and uncommon metabolites of Baicalin in rat urine for the universal understanding of the metabolism of Baicalin.
Materials and methods
Standard of Baicalin was purchased from the National Institute for the Control of Pharmaceutical and Biological Products (Beijing, China). Formic acid (HPLC grade) was purchase from DIKMA Technologies Inc. (Lake Forest, CA, USA). Acetonitrile (HPLC grade) was purchase from Fisher (USA). The distilled water was purchased from Watson's Food & Beverage Co., Ltd. (Guangzhou, China). Leucine enkephalin was purchased from Sigma-Aldrich (St. Louis, MO, USA).Male Wistar rats (220±20 g in weight) were kept in the breeding room with temperature (25°C), humidity (60 ± 5%) and under 12:12-h light-dark cycle conditions,divided into 2 groups
