蠅子草屬植物化學(xué)成分及藥理作用研究進(jìn)展

梁卓菲，梁小飛，吳國(guó)慶，李玉澤，黃文麗，張化為，姜 祎，宋小妹, 2*

蠅子草屬植物化學(xué)成分及藥理作用研究進(jìn)展

梁卓菲1，梁小飛1，吳國(guó)慶1，李玉澤1，黃文麗1，張化為1，姜 祎1，宋小妹1, 2*

1. 陜西中醫(yī)藥大學(xué)藥學(xué)院，陜西 咸陽(yáng) 712046 2. 陜西省中藥基礎(chǔ)與新藥研究重點(diǎn)實(shí)驗(yàn)室，陜西 咸陽(yáng) 712046

蠅子草屬植物資源豐富，全球超過(guò)400種，是世界上最大的屬之一，在民間具有悠久的用藥歷史。該屬化學(xué)成分復(fù)雜，包括蛻皮激素、三萜皂苷、生物堿等多種類結(jié)構(gòu)，具有抗菌、抗?jié)?、抗腫瘤、免疫調(diào)節(jié)、鎮(zhèn)痛抗炎、抗心律失常等藥理作用。但目前關(guān)于蠅子草屬植物綜述性報(bào)道較少，通過(guò)對(duì)CNKI、PubMed等數(shù)據(jù)庫(kù)，對(duì)近30年關(guān)于蠅子草屬化學(xué)成分及藥理作用相關(guān)研究的文獻(xiàn)展開(kāi)綜述，為后續(xù)深入研究蠅子草屬植物提供參考。

蠅子草屬；蛻皮激素；三萜皂苷；鎮(zhèn)痛抗炎；抗菌

石竹科蠅子草屬L.植物在全球已經(jīng)發(fā)現(xiàn)約400種，主要分布北半球溫帶以及非洲和南美洲地區(qū)，我國(guó)有112種、2亞種、17變種，廣布長(zhǎng)江流域和北部各省，目前已研究報(bào)道的蠅子草屬植物有L.L.L.L.L.L.L.L.L.L.L.L.L.L.等35種。該屬植物化學(xué)成分復(fù)雜，植物蛻皮激素類含量高、結(jié)構(gòu)豐富，具有化學(xué)分類學(xué)價(jià)值。蠅子草屬中九子參L.和瓦草L.為云南等地民間常用藥，用藥歷史悠久，常用來(lái)治療風(fēng)濕骨痛、癰腫和腫痛等證?，F(xiàn)代藥理研究表明，蠅子草屬植物具有抗心律失常、抗?jié)?、抗菌、抗腫瘤、中樞抑制、免疫調(diào)節(jié)等作用。目前國(guó)內(nèi)外對(duì)于蠅子草屬的研究較少，對(duì)該屬植物的藥效物質(zhì)基礎(chǔ)研究不夠全面，因此本文對(duì)蠅子草屬現(xiàn)有的文獻(xiàn)進(jìn)行總結(jié)，主要包括化學(xué)成分和藥理作用的綜述，為后續(xù)研究該屬植物提供參考。

1 化學(xué)成分

蠅子草屬植物化學(xué)成分豐富，近30年來(lái)，共從29個(gè)蠅子草屬植物中總結(jié)化合物159種，新化合物89種，主要是蛻皮激素和三萜皂苷，其他類型化合物有黃酮、生物堿、甾醇等。

1.1 蛻皮激素及其苷類

蛻皮激素類化合物是蠅子草屬中重要的一類化合物，蠅子草屬被認(rèn)為是新的蛻皮激素類似物很好的來(lái)源。苷元部分甾體母核上有多個(gè)羥基取代，C6上有羰基，C7有雙鍵，A/B環(huán)大多為順式稠合，個(gè)別為反式，且反式者無(wú)蛻皮活性或活性減弱。目前共從蠅子草屬植物中分離得到86個(gè)蛻皮激素及其衍生物類化合物，其中包括40個(gè)新化合物，其中，Dzhukarova課題組從L.地上部位分離出2個(gè)新化合物蠅子草甾苷F（sileneoside F）[1]和5α-2-去氧-α-蛻皮素-3--β--吡喃葡萄糖苷（5α-2-deoxy-α-ecdysone- 3--β--glucopyranoside）[2]，地下部位分離出1個(gè)新化合物2-去氧-20-羥基蛻皮素-20,22-單縮丙酮（2-deoxy-20-hydroxyecdysone- 20,22-monoacetonide）。Ramazonov課題組從L.植物中分離出2個(gè)新化合物短絨蠅子草甾酮（tomentesterone）A[3]和B[4]，并對(duì)蠅子草屬的4種植物L(fēng).、L.、L.和L.測(cè)定了6種蛻皮激素類化合物積累與植物發(fā)育階段的動(dòng)態(tài)關(guān)系[5]。Bathori從蠅子草屬的3種植物（L.、L.和L.）中共分離得到8個(gè)新化合物[6]。Mamadalieva等[7]在不同時(shí)間分別從中分離出2個(gè)新化合物。Saatov課題組經(jīng)過(guò)對(duì)蠅子草屬植物L(fēng).、L.、L.和L.的研究共發(fā)現(xiàn)6個(gè)新化合物[8-13]。Meng等[14]對(duì)蠅子草屬10個(gè)含蛻皮激素的植物進(jìn)行了分離和鑒定，并利用高效液相色譜法對(duì)6個(gè)主要化學(xué)成分的含量進(jìn)行了測(cè)定，有助于了解蛻皮激素類化合物在蠅子草屬植物中的分布。具體見(jiàn)表1和圖1，表2和圖2。

表1 蠅子草屬植物中的蛻皮激素類成分

續(xù)表1

編號(hào)化合物名稱來(lái)源文獻(xiàn) 372-deoxy-α-ecdysone 3-O-acetate 22-O-benzoateB11 38*2-deoxy-α-ecdysone 3,22-diacetateN8 39*2-deoxy-α-ecdysone 22-O-acetateG、J、K、N2,3,6,8 405α-2-deoxy-α-ecdysone 22-O-acetateG3 41*α-ecdysone 22-sulphateJ9 42*5α-2-deoxy-α-ecdysone 3-O-β-D-glucopyranosideJ1 43polypodin BC、E、F、G、H、I、J、P、Q、R3,5,10,15,16,19,25,28 4426-hydroxypolypodin BH、I18,32 45*2-deoxypolypodin B 3-O-β-D-glucopyranosideR15 46viticosterone EB、C、G、I、J、M3,11,16,32,10,22 47*viticosterone E 22-O-benzoateB12 48viticosterone E 2,3-diacetate 22-O-benzoateB12 49sileneoside AH、J、T5,10,18 50*sileneoside BJ10 51sileneoside CJ10 52sileneoside DF、G、H、J3,5,10,33 53*sileneoside EJ20 54*sileneoside FJ1 55*sileneoside GJ34 56*sileneoside HJ35 57*3-O-[α-D-galactopyranosyl-(1→6)-α-D-galactopyranosyl]-20-hydroxyecdysoneF33 58*tomentesterone AG25 59*tomentesterone B G25 60tomentesterone B 3,22-diacetateG4 6125S-inocosteroneQ、R15 62ponasterone AD、R15,17 63brahuisteroneJ1 64*ecdysterone 22,25-di-O-benzoateN36 652,22-diacetate-20,26-dihydroxyecdysoneH18 6620,26-dihydroxyecdysoneI32 6720-hydroxyecdysone-2-O-acetateI32 6826-hydroxyintegristerone AI32 693,22-diacetate-20,26-dihydroxyecdysoneH18 70*ecdysterone 20,22-monoacetonideN13 71ecdysterone 2,3;20,22-diacetonideN13 72ecdysterone 2,3-monoacetonide 22-O-benzoateN36 73ecdysterone 2,3-monoacetonideN36 74*2-deoxy-20-hydroxyecdysone 20,22-monoacetonideJ2 752-deoxy-21-hydroxyecdysoneR15 76*nusilsteroneE37 77*5β-cholest-7-ene-2β,3β,14α,20R,22R,25-hexahydroxy-6-on-20,22-acetal isovaleric aldehydeO38 78*5β-cholest-7-ene-2β,3β,14α,20R,22R,25-hexahydroxy-6-on-20,22-acetal epiisovaleric aldehydeO38 79*dihydropoststeroneK6 80dacryhainansteroneD17 81abutasteroneS26 82stachysterone AS26 8315-hydroxystachysterone AS26 84tukesteroneC、I16,32 85sidisteroneR15 86*20-hydroxyecdysone 20,22-monoacetonide 25-acetateH39

*表示從蠅子草屬植物中分離得到的新化合物 A-L. B-L. C-L. D-L. E-L. F-L. G-L. H-L. I-L. J-L. K-L. L-L. M-L. N-L. O-L. P-L. Q-L. R-L. S-L. T-L. U-L. V-L. W-L. X-L. Y-L. Z-L. a-L. b-L.c-L.，下同

*denotes a new compound isolated fromA-L. B-L. C-L. D-L. E-L. F-L. G-L. H-L. I-L. J-L. K-L. L-L. M-L. N-L. O-L. P-L. Q-L. R-L. S-L. T-L. U-L. V-L. W-L. X-L. Y-L. Z-L. a-L. b-L.c-L.，same as below

圖1 蠅子草屬植物中蛻皮甾醇類成分的母核結(jié)構(gòu)

1.2 三萜皂苷類

三萜皂苷是蠅子草屬植物中極性較大的一類化合物，苷元部分都是五環(huán)三萜類，基本母核為齊墩果烷型，基本碳架是多氫蒎的五環(huán)母核，環(huán)的構(gòu)型為A/B環(huán)，B/C環(huán)，C/D環(huán)均為反式，而D/E環(huán)為順式，C-3和C-28位一般連有較多數(shù)目的糖基。目前從本屬植物中共分離得到55個(gè)化合物，45個(gè)為新發(fā)現(xiàn)的化合物。Fu等[40-41]對(duì)云南九子參根中水溶性部位分離出9個(gè)新化合物九子參皂苷（silenorubicoside）A～I(xiàn)（87～95），譚寧華等[42]從九子參中得到4個(gè)糖鏈上帶乙?；男氯圃碥?乙酰九子參皂苷（rubicunoside）A～D（111～114）。Takahashi等[43]對(duì)日本產(chǎn)高雪輪L.中分離出一系列的三萜皂苷，其中代表性的有7個(gè)新化合物高雪輪皂苷（armeroside）A～G（116、123、125～128、130）。Bechkri等[44]對(duì)采自阿爾及利亞?wèn)|北部的高盧蠅子草L.中得到11個(gè)新三萜皂苷高盧蠅子草皂苷（silenegallisaponin）A～K（131～141），具體見(jiàn)表3和圖3，表4和圖4。

表2 蠅子草屬植物中的蛻皮激素類成分的結(jié)構(gòu)

續(xù)表2

編號(hào)取代基 R1R2R3R4R5R6R7R8 R9 30HHOAcβ-Hα-HOHOAcOHH 31HHOAcα-Hα-HOHOHOHH 32HHaβ-Hα-HOHOHOHH 33HHOHβ-Hα-HOHOHOHOH 34HHOHβ-Hα-HHβ-O-GlcOHH 35HHOHβ-Hα-HHOBzOHH 36HHOAcβ-Hα-HHOHOHH 37HHOAcβ-Hα-HHOBzOHH 38HHOAcβ-Hα-HHOAcOHH 39HHOHβ-Hα-HHOAcOHH 40HHOHα-Hα-HHOAcOHH 41HHOHβ-Hα-HHbOHH 42HHβ-O-Glcα-Hα-HHOHOHH 43HOHOH β-OHα-HOHOHOHH 44HOHOH β-OHα-HOHOHOHOH 45HHβ-O-Glc β-OHα-HOHOHOHH 46HOHOHβ-Hα-HOHOHOAcH 47HOHOHβ-Hα-HOHOBzOAcH 48HOAcOAcβ-Hα-HOHOBzOAcH 49HOHOHβ-Hα-HOHα-O-GalOHH 50HOHα-O-Galβ-Hα-HOHα-O-GalOHH 51β-OHOHOHβ-Hα-HOHα-O-GalOHH 52HOHα-O-Galβ-Hα-HOHOHOHH 53HHβ-O-Glcβ-Hα-HHOHOHH 54HHβ-O-Glcα-Hα-HHOHOHH 55HOHα-O-Galβ-Hα-HOHα-O-GlcOHH 56β-OHOHOHβ-Hα-HOHα-O-GalOAcH 57HOHcβ-Hα-HOHOHOHH 58HHOHβ-Hα-HHOAcOBzH 59HHOHβ-Hα-HHOHOBzH 60HHOAcβ-Hα-HHOAcOBzH 61HOHOHβ-Hα-HOHOHOHOH 62HOHOHβ-Hα-HOHOHHH 63HHOH β-OHα-HHOHOHH 64HOHOHβ-Hα-HOHOBzOBzH 65HOAcOHβ-Hα-HOHOAcOHOH 66HOHOHβ-Hα-HOHOHOHOH 67HOAcOHβ-Hα-HOHOHOHH 68β-OHOHOHβ-Hα-HOHOHOHOH 69HOHOAcβ-Hα-HOHOAcOHOH a-巴豆鹽酸 b-鹽酸鹽 c-3-O-[α-D-葡萄糖(1→6)-α-D-葡萄糖]a-crotonate b-sulfate c-3-O-[α-D-gal(1→6)-α-D-gal]nn

a-巴豆鹽酸 b-鹽酸鹽 c-3--[α--葡萄糖(1→6)-α--葡萄糖]

a-crotonate b-sulfate c-3--[α--gal(1→6)-α--gal]

表3 蠅子草屬植物中的三萜皂苷類成分

續(xù)表3

編號(hào) 化合物名稱來(lái)源文獻(xiàn) 123*armeroside BZ43 124 sinocrassuloside IZ43 125*armeroside CZ43 126*armeroside DZ43 127*armeroside EZ43 128*armeroside FZ43 129 saponarioside KZ43 130*armeroside GZ43 131* silenegallisaponin Aa44 132* silenegallisaponin Ba44 133* silenegallisaponin Ca44 134* silenegallisaponin Da44 135* silenegallisaponin Ea44 136* silenegallisaponin Fa44 137* silenegallisaponin Ga44 138* silenegallisaponin Ha44 139* silenegallisaponin Ia44 140* silenegallisaponin Ja44 141* silenegallisaponin Ka44

表4 蠅子草屬植物中的三萜皂苷類成分的結(jié)構(gòu)

續(xù)表4

編號(hào)苷元類型取代基R1取代基R2 112IIIβ-D-galactopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucuronopyranosylβ-D-xylopyranosyl-(1→3)-β-D-xylopyra-nosyl-(1→4)-α-L-rhamno-pyranosyl-(1→4)-[β-D-glucopyranosyl-(1→4')-β-D-quinovopyranosyl-(1→2)]-3'-O-acetyl-β-D-fucopyranosyl 113IIIβ-D-galactopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucuronopyranosylβ-D-xylopyranosyl-(1→4)-α-L-rhamnop-yranosyl-(1→4)-[4''-O-acetyl-β-D-glucopyranosyl-(1→2)]-β-D-fucopyranosyl 114IIIβ-D-galactopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-[6'-O-butyl]-β-D-glucuronopyranosylβ-D-xylopyranosyl-(1→3)-β-D-xylopyra-nosyl-(1→4)-α-L-rhamno-pyranosyl-(1→4)-[2''-O-acetyl-β-D-quinovopyranosyl-(1→2)]-3'-O-acetyl-β-D-fucopyranosyl 115IIIβ-D-galactopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucuronopyranosylH 116IIIβ-D-galactopyranosyl-(1→2)-β-D-glucuronopyranosylα-L-rhamnopyranosyl-(1→2)-[ β-D-gluc-opyranosyl-(1→3)]-4-O-acetyl-β-D-fucopyranosyl 117IIIβ-D-galactopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-6-O-butyl-β-D-glucuronopyranosylα-L-rhamnopyranosyl-(1→2)-[3-O-acetyl-4-O-trans-p-methoxycinnamoyl]-β-D-fucopyranosyl 118IIIβ-D-galactopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-6-O-butyl-β-D-glucuronopyranosylα-L-rhamnopyranosyl-(1→2)-[3-O-acetyl-4-O-cis-p-methoxycinnamo-yl]-β-D-fucopyranosyl 119IIIH{α-D-mannopyranosyl-(1→4)-[α-D-gala-ctopyranosyl-(1→6)]-β-D-glucopyranosyl-(1→3)}-[β-D-6-O-((3R)-3-hydroxy-3- methylglutaryl)-glucopyranosyl-(1→6)]-β-D-glucopyranosyl 120IIIβ-D-galactopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-6-O-methyl-β-D-glucuronopyranosylα-L-rhamnopyranosyl-(1→2)-3-O-acetyl-4-O-trans-p-methoxycinnamoyl-β-D-fuc-opyranosyl 121IIIβ-D-galactopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-6-O-methyl-β-D-glucuronopyranosylα-L-rhamnopyranosyl-(1→2)-3-O-acetyl-4-O-cis-p-methoxycinnamoyl-β-D-fucopyranosyl 122IVHβ-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl 123IVHβ-D-glucuronopyranosyl-(1→2)-β-D-glucopyranosyl 124IVHβ-D-glucopyranosyl-(1→3)-[β-D-glucopyranosyl-(1→6)]-β-D-glucopyranosyl 125IVHβ-D-glucuronopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→6)]-β-D-glucopyranosyl 126Xβ-D-glucopyranosylβ-D-(1→3)-[β-D-glucopyranosyl-(1→6)]-β-D-glucopyranosyl 127IVH[β-D-6-O-((3S)-3-hydroxy-3-methylglutaryl)-glucopyranosyl-(1→3)]-[β-D-glucopyranosyl-(1→6)]-β-D-glucopyranosyl 128XIHβ-D-glucopyranosyl-(1→3)-[β-D-glucopyranosyl-(1→6)]-β-D-glucopyranosyl 129VHβ-D-glucopyranosyl-(1→3)-[β-D-glucopyranosyl-(1→6)]-β-D-glucopyranosyl 130VH[β-D-6-methyl-glucuronopyranosyl-(1→2)]-[β-D-glucopyranosyl-(1→6)]-β-D-glucopyranosyl 131VIβ-D-glucuronopyranosylβ-D-glucopyranosyl-(1→3)-[β-D-glucopyranosyl-(1→2)]-β-D-fucopyranosyl 132VIβ-D-glucuronopyranosylβ-D-glucopyranosyl-(1→3)-[3-O-acetyl-β-D-glucopyranosyl-(1→2)]-β-D-fucopyranosyl 133VIβ-D-glucuronopyranosyl[3-O-acetyl-β-D-glucopyranosyl-(1→2)]-β-D-fucopyranosyl 134VIβ-D-glucuronopyranosylβ-D-glucopyranosyl-(1→3)-[6-O-acetyl-β-D-glucopyranosyl-(1→2)]-β-D-fucopyranosyl 135XIIβ-D-glucuronopyranosylβ-D-glucopyranosyl-(1→3)-[3-O-acetyl-β-D-glucopyranosyl-(1→2)]-β-D-fucopyranosyl 136IIIβ-D-glucuronopyranosylβ-D-glucopyranosyl-(1→3)-[3-O-acetyl-β-D-glucopyranosyl-(1→2)]-β-D-fucopyranosyl 137VIβ-D-galactopyranosyl-(1→3)-β-D-glucuronopyranosyl β-D-glucopyranosyl-(1→3)-[β-D-glucopyranosyl-(1→2)]-β-D-fucopyranosyl 138VIβ-D-galactopyranosyl-(1→3)-β-D -glucuronopyranosylβ-D-glucopyranosyl-(1→3)-[6-O-acetyl-β-D-glucopyranosyl-(1→2)]-β-D-fucopyranosyl 139VIβ-D-glucuronopyranosylβ-D-quinovopyranosyl-(1→3)-[3-O-acetyl-β-D-glucopyranosyl-(1→2)]-β-D-fucopyranosyl 140VIβ-D-glucuronopyranosylβ-D-quinovopyranosyl-(1→3)-[β-D-glucopyranosyl-(1→2)]-β-D-fucopyranosyl 141VIβ-D-galactopyranosyl-(1→3)-β-D-glucuronopyranosylβ-D-quinovopyranosyl-(1→3)-[β-D-glucopyranosyl-(1→2)]-β-D-fucopyranosyl

1.3 其他化合物

Seo等[52]從分離出8個(gè)化合物，其中包括4個(gè)新生物堿類化合物siliendines A～D（142～145）；Zemtsova等[53]從L.中分離出4個(gè)黃酮類化合物；王童等[54]從瓦草的乙醇提取物中分離出13個(gè)化合物，10個(gè)為該植物首分。具體結(jié)構(gòu)見(jiàn)圖4和表5。

圖4 蠅子草屬植物中其他類成分的結(jié)構(gòu)

2 藥理作用

2.1 抗心律失常

Golovko等[55]研究發(fā)現(xiàn)從L.植物中得到的果膠多糖—蠅子草果聚糖（silenan）可糾正青蛙心臟竇房區(qū)細(xì)胞間動(dòng)作電位傳導(dǎo)紊亂，主要表現(xiàn)在心律失常的產(chǎn)生和動(dòng)作電位傳播受損等方面，蠅子草果聚糖增加了鹽水的黏度，并形成了與自由羧基數(shù)量呈比例的親水絡(luò)合物，能使心臟竇房區(qū)電活動(dòng)穩(wěn)定，從而達(dá)到抗心律失常的作用。

表5 蠅子草屬植物中的其他類成分

2.2 抗?jié)冏饔?/h3>

Krylova等[56]對(duì)含蛻皮激素的植物L(fēng).和L.的提取物進(jìn)行了抗?jié)兓钚匝芯?，結(jié)果表明提取物能顯著降低乙酰水楊酸所致潰瘍模型的破壞作用，抑制COX-1和COX-2的釋放，說(shuō)明提取物具有增強(qiáng)黏膜屏障的保護(hù)作用和黏膜對(duì)前列腺素合成的抵抗力。

2.3 抗菌作用

Kucukboyaci等[57]通過(guò)體外抑菌實(shí)驗(yàn)發(fā)現(xiàn)，L.和L.種子石油醚提取物都對(duì)革蘭陰性菌肺炎鏈球菌有顯著的抑菌活性，最小抑菌濃度（MIC）為4 μg/mL，對(duì)白色念珠菌生長(zhǎng)有較強(qiáng)的的抗菌活性，MIC為16 μg/mL。此外，2種樣品提取物對(duì)大腸桿菌和奇異桿菌有一定的抑制作用，MIC為32 μg/mL，對(duì)金黃色葡萄球菌和枯草桿菌活性的MIC為64 μg/mL。在抗菌方面具有廣闊的發(fā)展前景。Mamadalieva等[58]研究發(fā)現(xiàn)，L.三氯甲烷提取物對(duì)大腸桿菌鮑曼不動(dòng)桿菌和綠膿桿菌生長(zhǎng)均有不同程度的抑制作用。Bajpai等[59]以水蒸氣蒸餾法提取L.中的揮發(fā)油成分，并測(cè)試總揮發(fā)油抗真菌作用，結(jié)果表明總揮發(fā)油對(duì)辣椒疫霉、赤霉病菌、辣椒炭疽菌、菌核病菌、灰霉病菌和大豆根瘤菌均有顯著的抑菌作用，抑菌幅度為39.6%～67.6%，MIC值為62.5～1000 μg/mL，因此，L.揮發(fā)油具有廣泛的殺真菌活性。

2.4 抗腫瘤作用

Mamadalieva等[58]采用MTT試驗(yàn)法評(píng)價(jià)細(xì)胞毒活性，體外研究表明.L.三氯甲烷提取物能抑制宮頸癌HeLa細(xì)胞的增殖，抑制質(zhì)量濃度為26.58 μg/mL，與對(duì)照組相比，50%的細(xì)胞死亡，說(shuō)明該提取物具有抗腫瘤活性。馬倩等[60]研究，化合物（104～105）對(duì)宮頸癌HeLa細(xì)胞有較強(qiáng)的抑制作用，半數(shù)抑制濃度（IC50）為2.37 μmol/L?；衔铮?04～105）誘導(dǎo)HeLa細(xì)胞凋亡是通過(guò)下調(diào)細(xì)胞周期蛋白（cyclin D1）的表達(dá)和降低Rb蛋白的磷酸化水平，使HeLa細(xì)胞阻滯在G1期。同時(shí)，化合物（104～105）通過(guò)上調(diào)p16蛋白水平和增加β半乳糖酶染色細(xì)胞的數(shù)量誘導(dǎo)HeLa細(xì)胞衰老[60]。

2.5 中樞抑制作用

鄺荔香等[61]研究表明，九子參總皂苷對(duì)中樞神經(jīng)系統(tǒng)有抑制作用，可減少小鼠自發(fā)活動(dòng)，協(xié)同戊巴比妥催眠并有一定的鎮(zhèn)痛作用，無(wú)對(duì)抗戊四氮和電休克驚厥作用，提高小鼠的耐缺氧能力，小鼠ig的半數(shù)致死量（LD50）為1.65 g/kg。

2.6 免疫調(diào)節(jié)作用

Shakhmurova等[62]在輻射、急性毒性肝炎和長(zhǎng)時(shí)間的體力負(fù)荷條件下，觀察從L.中分離的總蛻皮激素對(duì)正常動(dòng)物和繼發(fā)性免疫缺陷小鼠對(duì)免疫系統(tǒng)的影響，結(jié)果表明總蛻皮激素的免疫調(diào)節(jié)活性可與已知的免疫刺激劑T-activin相媲美，說(shuō)明總蛻皮激素具有有效的免疫調(diào)節(jié)作用。

2.7 酶抑制作用

Mamadalieva等[63]通過(guò)對(duì)乙酰膽堿酯酶、丁基膽堿酯酶、酪氨酸酶、淀粉酶和糖苷酶的評(píng)價(jià)，從L.的提取物和分離的化合物表現(xiàn)出相當(dāng)大的酶抑制潛力，抗膽堿酯酶能力按順序排列：20-羥基蛻皮素＞2-去氧-20-羥基蛻皮素＞甲醇提取物＞2-去氧蛻皮素。值得注意的是，甲醇提取物的抗酪氨酸酶和抗淀粉酶作用最強(qiáng)。

2.8 抗氧化作用

Mamadalieva等[63]對(duì)L.植物不同提取方式提取物進(jìn)行了抗氧化活性研究，根據(jù)研究結(jié)果，甲醇提取物對(duì)清除DPPH自由基表現(xiàn)出中等活性，浸提液對(duì)銅離子（34.37 mg/g）的還原活性高于對(duì)照鐵離子（22.19 mg/g）。同時(shí)，萃取物也是一種良好的金屬螯合劑EDTAE，其值為11.23 mg/g。

2.9 抗炎鎮(zhèn)痛作用

Ghonime等[64]對(duì)生長(zhǎng)在埃及的3種蠅子草屬藥用植物提取物進(jìn)行研究，發(fā)現(xiàn)L.和L.提取物能抑制一氧化氮合酶（iNOS）表達(dá)和腫瘤壞死因子（TNF）-α活性，從而降低誘導(dǎo)巨噬細(xì)胞產(chǎn)生的一氧化氮（NO）；L.和L.能顯著抑制巨噬細(xì)胞刺激后產(chǎn)生的COX-2表達(dá)。張冠慶[65]發(fā)現(xiàn)，在FAC所致的大鼠足趾腫脹模型中，瓦草的正丁醇部位能緩解大鼠關(guān)節(jié)腫脹，抗炎機(jī)制可能與抑制血清中炎癥因子白介素（IL）1-β、TNF-α的表達(dá)有關(guān)。

2.10 抑制淋巴細(xì)胞增殖

Gaidi等[47]的實(shí)驗(yàn)證實(shí)，皂苷化合物（107～110）在高濃度（10 μmol/L）時(shí)能抑制T淋巴細(xì)胞DNA合成，從而抑制細(xì)胞增殖，誘導(dǎo)細(xì)胞凋亡。

3 討論

蠅子草屬植物資源廣泛，全球各地均有分布，國(guó)外研究者較多，以化學(xué)成分和藥理研究為主，化學(xué)成分多以分離新化合物為主要目標(biāo)，藥理作用主要為提取物的活性研究。本文對(duì)蠅子草屬近年來(lái)的相關(guān)文獻(xiàn)進(jìn)行了總結(jié)并整理出最新的單體化合物，報(bào)道較多的是蛻皮激素和三萜皂苷類，其他類型化合物報(bào)道較少，今后的研究者可從其他類型化合物入手，豐富蠅子草屬化合物的結(jié)構(gòu)類型。其中，蛻皮激素為該屬植物的標(biāo)志性化合物，含量高、結(jié)構(gòu)豐富，具有調(diào)節(jié)糖代謝、免疫調(diào)節(jié)和治療風(fēng)濕、關(guān)節(jié)炎等藥理作用，我國(guó)傳統(tǒng)著名中藥牛膝及其同屬植物中，蛻皮激素為主要化學(xué)成分[66]，牛膝屬植物的療效確切，臨床應(yīng)用廣泛，蠅子草屬植物可做為其代替品，也可作為生產(chǎn)蛻皮激素的原料植物。近年來(lái)，對(duì)蠅子草屬藥理方面的研究有所增加，主要集中在抗菌、抗氧化、抗炎、抗腫瘤等方面，其中，大多數(shù)蠅子草屬的植物提取物具有不同程度的抗菌作用，抗菌作用廣泛。但對(duì)單體化合物的藥理活性研究較少，只進(jìn)行了初步的活性篩選，沒(méi)有進(jìn)行深入的機(jī)制研究，未能闡明抗菌物質(zhì)基礎(chǔ)。仍需進(jìn)一步分離和篩選單體化合物，結(jié)合藥物靶點(diǎn)，深入研究分子機(jī)制，尋找活性好、毒性低的天然產(chǎn)物進(jìn)行藥品的研發(fā)。

利益沖突 所有作者均聲明不存在利益沖突

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Advances on chemical constituents and pharmacological activities of

LIANG Zhuo-fei1, LIANG Xiao-fei1, WU Guo-qing1, LI Yu-ze1, HUANG Wen-li1, ZHANG Hua-wei1, JIANG Yi1, SONG Xiao-mei1, 2

1.Shaanxi University of Chinese Medicine, College of pharmacy, Xianyang 712046, China 2. Shaanxi Key Laboratory of Traditional Chinese Medicine Foundation and New Drug Research, Xianyang 712046, China

is one of the largest genera in the world with abundant plant resources and over 400 species, which has a long history of medicines in the folk. The chemical constituents of the genusare complex, including ecdysteroids, triterpenoid saponins, alkaloids, and other structures, which have the pharmacological activities of antibacterial, anti-ulcer, anti-tumor, immune regulation, analgesic, anti-inflammatory, anti-arrhythmia, etc. However, there are currently few articles about the genera of. This paper reviewed the literatures on the chemical constituents and pharmacological effects ofin the past 30 years through CNKI, PubMed, and other databases to provide references for the further study on the genera of.

L.; ecdysteroids; triterpenoid saponins; analgesic; antibacterial

R286.6

A

0253 - 2670(2021)07 - 2184 - 15

10.7501/j.issn.0253-2670.2021.07.035

2020-09-06

陜西省科技廳項(xiàng)目（2019ZDLSF04-03-02）；陜西中醫(yī)藥大學(xué)學(xué)科創(chuàng)新團(tuán)隊(duì)項(xiàng)目（2019-YL12）

梁卓菲，碩士研究生，研究方向?yàn)橹胁菟幩幮镔|(zhì)基礎(chǔ)研究。E-mail: 18391000138@163.com

宋小妹，教授，研究方向?yàn)橹兴幩幮镔|(zhì)基礎(chǔ)研究。E-mail: songxiaom@126.com

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