王曉玲，袁綠益

(西南民族大學(xué)藥學(xué)院，四川 成都 610041)

獅耳花的藥學(xué)研究進(jìn)展

王曉玲，袁綠益

(西南民族大學(xué)藥學(xué)院，四川 成都 610041)

目的綜合報道獅耳花在植物學(xué)，藥理學(xué)，植物化學(xué)，生物活性，毒理學(xué)及其商業(yè)方面的研究.方法對1900年～2015年的文獻(xiàn)進(jìn)行廣泛查閱，包括電子數(shù)據(jù)庫Scopus，SciFinder，Pubmed，Google Scholar中的摘要，全文文章和相關(guān)書籍.結(jié)果獅耳花中主要含萜類化合物，尤其是半日花烷型二萜類.還有很多化學(xué)成分被認(rèn)為并非來自獅耳花，比如，具有輕度神經(jīng)興奮性的益母草堿，從未出現(xiàn)在獅耳花提取物中.結(jié)論盡管對獅耳花的研究和應(yīng)用已有很多報道，但是仍需要對該植物中的未知成分進(jìn)行深入研究，尤其對有神經(jīng)性作用的相關(guān)成分進(jìn)行系統(tǒng)分離和鑒定，具有重要的學(xué)術(shù)價值.

獅耳花；半日花烷型二萜類；藥理活性

獅耳花Leonotis leonurus(L.)R.Br.系唇形科獅耳花屬常綠灌木，淺棕色方莖，全株密被柔毛，幼株莖纖細(xì)，灰綠色.單葉對生，葉片紙質(zhì)或亞革質(zhì)，通常鐮狀橢圓形，有時為長圓狀披針形或倒披針形，具粗鋸齒，表面綠色，背面淡綠色，氣味刺鼻，花叢生于莖上部葉腋處，長40至70毫米，花序柄圓柱形，花萼12到16毫米長，直徑4毫米，筒狀花冠40至49毫米長，橙色并且覆蓋橙色毛[1-2].

獅耳花的名字起源于希臘文，“l(fā)eon”譯為獅子，“otis”譯為耳朵，并因其花瓣長得像獅子的耳朵，故取名為獅耳花(如圖1)[3].

圖1 獅耳花Fig.1 Leonotis leonurus

2 民間應(yīng)用

2.1 人類疾病治療

獅耳花，俗稱野生大麻，同時具有藥用價值和神經(jīng)興奮作用，廣泛用于如痔瘡、濕疹、皮疹、癤子、瘙癢、肌肉痙攣、頭痛，癲癇，胸部感染，便秘，蜘蛛和蛇咬傷的治療[4].詳細(xì)的用藥過程是取一湯匙切碎的干葉子(約10g)，加入三杯開水煎煮10分鐘，冷卻一夜，過濾后清洗傷口[5].煎煮后的獅耳花還可以作為治療咳嗽，感冒和支氣管炎的口服藥.獅耳花的粉末可做成藥膏，局部使用可緩解眼部疼痛[6].獅耳花干粉或種子煎煮后可作為緩解痔核的口服藥物，局部使用可緩解頭部和腿部潰爛.根據(jù)Watt和Breyer-Brandwijk報道，獅耳花葉煎煮后可用作瀉藥和調(diào)經(jīng)劑[7].獅耳花的莖、葉和花通過煎煮或吸食可治療普通感冒、癲癇、麻風(fēng)、高血壓[8].

獅耳花的葉和花在非洲南部常用于治療胸部感染、流感、發(fā)燒、痢疾、便秘、頭痛、癲癇、蜘蛛和蛇咬傷、月經(jīng)推遲、腸道蠕蟲、高血壓、蝎子刺[6，9-12].在治療蛇咬傷時，經(jīng)常將獅耳花的根部與其他植物混合使用，如獅耳花與馬錢子刺混合，趁熱口服作催吐劑[9].在南非，祖魯人用熱水浸泡后的莖和葉子治療咳嗽和感冒，用冷水浸泡后的葉子沖洗鼻腔來緩解高燒引起的頭痛.浸泡后的葉子還被報道可治療哮喘和緩解病毒性肝炎[7].Maroyi在2013年發(fā)表的對津巴布韋中南部地區(qū)傳統(tǒng)藥用植物綜述中表明，咀嚼吞咽獅耳花的葉可治療潰瘍[12].吸食獅耳花的葉和花可治療癲癇和局部麻痹[7，11].獅耳花葉經(jīng)常被用作薄荷茶杯沖泡使用，有助于利尿和治療肥胖[6-7，11].獅耳花的民間應(yīng)用詳見表1.

除了表1中的民間應(yīng)用外，獅耳花由于具有神經(jīng)興奮活性還可以用作商品銷售[6，11].據(jù)報道，吸食獅耳花的干燥花、葉具有減輕癲癇的作用，吸食過程中會產(chǎn)生一種類似大麻的作用，不過十分輕微[20].

2.2 傳統(tǒng)獸藥應(yīng)用

在許多發(fā)展中國家，畜牧農(nóng)民經(jīng)常使用本地植物來治療患病牲畜[21].草藥對動物的常見疾病，如輕度腹瀉、腸道寄生蟲、傷口和皮膚感染都有很好的療效，而且價廉易得，是農(nóng)民的首選方法.Masika和Afolayan等人發(fā)現(xiàn)，獅耳花葉的汁液滴入動物的眼睛可治療眼部炎癥[15-17].搗碎的根和葉添加于家禽的飲用水中可以預(yù)防疾病，治療牛邊蟲病[18].獅耳花也可以用來防止牲畜蠕蟲感染[19]，其水提物可以有效預(yù)防山羊胃腸道寄生蟲.

2.3 娛樂性使用

在21世紀(jì)初，許多草藥在互聯(lián)網(wǎng)上被宣傳為大麻的合法代替品[22].獅耳花就是其中的一種，其他如埃及藍(lán)睡蓮，透納樹葉.雖然這些都自稱是“純”草藥產(chǎn)品，但在2008年發(fā)現(xiàn)它們被摻入合成大麻類化合物.這些芳香植物實質(zhì)是作為幫助合成大麻類產(chǎn)品銷售的“綠色飛機(jī)”，這種做法會嚴(yán)重危害到公眾的健康[23].

表1 獅耳草的民間應(yīng)用Table 1 Traditional uses，preparation and mode of administration of Leonotis leonurus

3 化學(xué)成分

獅耳花中提取到的主要化合物有單萜類，倍半萜類和半日花烷型二萜類化合物[24～34]，見圖2.

圖2 獅耳花半日花烷型二萜類化合物基本結(jié)構(gòu)Fig.2 General structure of labdane diterpene

以半日花烷型為母核的二萜類化合物見表2，除二萜類化合物的其它化合物見表3.

表2 獅耳花半日花烷型二萜類化合物Table 2 Labdane diterpenoids from Leonotis leonurus

表3 獅耳花中的雜環(huán)化合物(除二萜類化合物)Table 3 Miscellaneous compounds，other than diterpenes，from Leonotis leonurus

4 藥理活性

獅耳花具有多方面的藥理活性，如抗驚厥、抗菌、抗感染、抗瘧、抗氧化、抗HIV等，獅耳花化學(xué)成分的藥理活性見表2和3.

5 總結(jié)

雖然關(guān)于獅耳花的化學(xué)成分及藥理活性已有大量報道，但是有很多成分仍需要權(quán)威的研究和闡明，包括獅耳花中的生物堿和精油，以及其它部位化學(xué)成分，比如傳統(tǒng)醫(yī)藥學(xué)中廣泛研究的根部.研究已證明獅耳花的粗提物中具有神經(jīng)性作用，所以對具有神經(jīng)性作用的成分進(jìn)行分離和鑒定就顯得尤為重要.在南非，獅耳花作為傳統(tǒng)民間草藥被廣泛使用，如果要為患者提供安全有效的產(chǎn)品，尚需在質(zhì)量控制方面做大量的工作.

[1]IWARSSON M，HARVEY Y.Monograph of the genus Leonotis[J].Kew Bulletin，2003，58:597-645.

[2]HURINANTHAN V.Immune Modulatory Effect of Dichrostachys cinerea，Carpobrotus dimidiatus，Capparis tomentosa and Leonotis leonurus [D].Durban:Durban University of Technology，2009.

[3]BAUDRY N N，GILL E，ALVARO V.“Wild cannabis”:A review of the traditional use and phytochemistry of Leonotis leonurus[J].Journal of Ethnopharmacology，2015，174:520-539.

[4]SCOTT G，SPRINGELD E P，COLDREY N.A pharmacognostical study of 26 South African plant species used as traditional medicines[J]. Pharmaceutical Biology，2004，42:186-213.

[5]MUGABO P，KHAN F，BURGER A.Effect of Leonotis leonurus aqueous extract on the isolated perfused rat heart[J].Journal of Medicinal and Aromatic Plant Sciences，2012，Plants 2:281-292.

[6]HUTCHINGS A，SCOTT A H，LEWIS G，et al.An Inventory[M].Natal，South Africa:University of Natal Press，1996:266-267.

[7]WATT J M，BREYER-BR，WIJK B N.Medicinal and poisonous plantsof Southern and Eastern Africa[M].2nd ed.Churchill Livingstone，Edinburgh，1962:514-520.

[8]DUKE J A.Handbook of medicinal herbs[M].2nd ed.London，New York，Washington D C，Boca Raton:CRC press，2001.

[9]BRYANT A T.Zulu medicine and medicine Men[M].Struik，Cape Town，1909.

[10]J?GER A K，HUTCHINGS A，VAN STADEN J.Screening of Zulu medicinal plants for prostagladin-synthesis inhibitors[J].Journal of Ethnopharmacology，1996，52:95-100.

[11]VAN WYK B E，VAN OUDSHOORN B，GERICKE，N.Medicinal Plants of South Africa[M].2nd edition.Briza Publications Pretoria，South Africa，2000.

[12]STAFFORD G I，PEDERSEN M E，VAN STADEN J，et al.Review on plants with CNS effects used in traditional South African medicine against mental diseases[J].Journal of Ethnopharmacology，2008，119: 513-537.

[13]MAROYI A.Traditional use of medicinal plants in south-central Zimbabwe:review and perspectives[J].Journal of Ethnobiology and Ethnomedicine，2013，9:31.

[14]MABONA U，VAN VUUREN S F.South African medicinal plants used to treat skin diseases.S.Afr[J].Pakistan Journal of Botany，2013，87: 175-193.

[15]MASIKA P J，SONANDI A，et al.Perceived causes，diagnosis and treatment of babesiosis and anaplasmosis in cattle by livestock farmers in communal areas of the central Eastern Cape Province，South Africa [J].Journal of the South African Veterinary Association，1997，68:40-44.

[16]MASIKA P J，VAN AVERBEEKE W，SONANDI A.Use of herbal remedies by smallscale farmers to treat livestock diseases in central Eastren Cape province，South Africa[J].Journal of the South African Veterinary Association，2000，71:87-91.

[17]MASIKA P J，AFOLAYAN A J.An ethnobotanical study of plants used for thetreatment of livestock diseases in the Eastern Cape Province，South Africa[J].Pharmaceutical Biology，2003，41:16-21.

[18]HULME M M.Wild Flowers of Natal[M].Shuter＆Shooter，Pietermaritzburg，1954.

[19]MAPHOSA V，MASIKA P J.In vivo validation of Aloe ferox(Mill) .Elephantorrhiza elephantina Bruch.Skeels.and Leonotis leonurus(L) R.Br as potential anthelmintics and antiprotozoals against mixed infections of gastrointestinal nematodes in goats[J].Parasitology Research，2011，110:103-108.

[20]WU H，LI J，F(xiàn)RONCZEK F R，et al.Labdane diterpenoids from Leonurus leonurus[J].Phytochemstry，2013，91:229-235.

[21]MCGAW L.J，ELOFF J N.Ethnoveterinary use of Southern African plants andscientific evaluation of their medicinal properties[J].Journal of Ethnopharmacology，2008，119:559-574.

[22]ZUBA D，GEPPERT B，SEKULA K，et al.[1-(Tetrahydropyran-4-ylmethyl)-1H-indol-30yl]-(2，2，3，3，-tetramethylcyclopropyl)methanone:a new synthetic cannabinoid identified on the drug market[J]. Forensic Toxicology，2013，31:281-291.

[23]CORNARA L，BORGHESI B，CANALI C，et al.Smart drugs:green shuttle or real drug[J].Journal of Legal Medicine，2013，127:1109-1123.

[24]DEMETZOS C，DIMAS S.Labdane-type diterpenes:chemistry and biological activity[J].Studies in Natural Products Chemistry，2001，35: 235-292.

[25]PURUSHOTHAMAN K K，VASANTH S.Chemical studies on Leonotis–a review[J].Indian Drugs，1988，25:484-491.

[26]PEDRO L G，BARROSO J G，MARQUES N T，et al.Composition of the essential oil from sepals of Leonotis leonurus R Br J Essent[J]. Journal of Essential Oil Research，1991，3:451-453.

[27]CRAGG G M L，LITTLE G E.The extractives of Leonotis leonurus [J].South African Journal of Chemistry，1962，15:29-30.

[28]RIVETT D E A.Isolation of marrubiin from Leonotis leonurus[J]. Chemical Society，1964:1857-1858.

[29]KAPLAN E R，RIVETT D E A.Structures of compounds X and Y，two labdane diterpenoids，from Leonotis leonurus[J].Chemical Society，1968:262-266.

[30]LAONIGRO G，LANZETTA R，PARRILLI M，et al.The conguration of the diterpene spiroethers from Marrubium vulgare and from Leonotis leonurus[J].Gazzella Chimica，1979，109:145-150.

[31]KRUGER G J，RIVETT D E A.Diterpenoids of Leonotis species.Part 7.The crystal and molecular structure of compound X a labdane from Leonotis leonurus[J].South African Journal of Chemistry，1988，41: 124-125.

[32]MCKENZIE J M，GREEN I R，MUGABO P.Leonurun，a novel labdane diterpenoid from Leonotis leonurus[J].South African Journal of Chemistry，2006，59:114-116.

[33]OBIKEZE K C，MCKENZIE J M，GREEN I R，et al.Characterization and cardiovascular effects of(13S)-9α，13α-epoxylabda-6β(19)，15 (14)diol dilactone，a diterpenoid isolated from Leonotis leonurus[J]. South African Journal of Chemistry，2009，61:119-122.

[34]NAIDOO D，MAHARAJ V，CROUCH N R，et al.New labdane-type diterpenoids from Leonotis leonurus support circumscription of Lamiaceae s.l.Biochemstry[J].Biochemical Systematics and Ecology，2011，39:216-219.

[35]BIENVENU E，AMABEOKU G J，EAGLES P K，et al.Anticonvulsant activity of aqueous extract of Leonotis leonurus[J].Journal Phytomedicine，2002，9:217-223.

[36]HE F，LINDQVIST C，HARDING W.Leonurenones A–C:labdane diterpenes from Leonotis leonurus[J].Journal Phytochemdicine，2012，83:168-172.

[37]VON DREELE R B，PETTIT G R，ODE R H，et al.The crystal and molecular structure of the unusual spiro dihydrofuran diterpene，nepe-taefolin[J].Journal of the American Chemical Society，1975，97:6236-6240.

[38]MNONOPI N，LEVENDAL R A，COLEMAN M，et al.The cardioprotectiveeffects of marrubiin，a diterpenoid found in Leonotis leonurus extracts[J].Journal of Ethnopharmacology，2011，138:67-75.

[39]MNONOPI N，LEVENDAL R A，MZILIKAZI N，et al.Marrubiin，a constituent of Leonotis leonurus，alleviates diabetic symptoms[J].Journal Phytomedicin，2012，19:488-493.

[40]POPOOLA K，ELBAGORY M，AMEER F，et al.Marrubiin:a review [J].Molecules，2013，18:9049-9060.

[41]NARUKAWA Y，KOMORI M，NIIMURA A，et al.Two new diterpenoids from Leonotis leonurus R Br[J].Nature Medicine，2015，69:130-134.

[42]CHEN C X，KWAN C Y.Endothelium-independent vasorelaxation by leonurine，a plant alkaloid purified from Chinese motherwort[J].Life Sciences，2001，68:953-960.

[43]KUCHTA K，ORTWEIN J，RAU W，et al.Leonurus japonicus，Leonurus cardiaca，Leonotis leonurus:a novel HPLC study on the occurrenceand content of the pharmacologically active guanidino derivative leonurine[J].Pharmazie，2012，67(12):973-979.

[44]LóPEZ L..Distribution and biological activities of the avonoid luteolin [J].Medical Chemical，2009，9:31-59.

[45]AGNIHOTRI V K，ELSOHLY H N，SMILLIE T J，et al.Constituents of Leonotis leonurus Flowering tops[J].Phytochemistry Letter，1991，2: 103-105.

[46]EL-ANSARI M A，ABOUTABL E A，F(xiàn)ARRAG A R H，et al.Phytochemical and pharmacological studies on Leonotis leonurus[J].Pharmaceutical Biology，1991，47:894-902.

[47]NISHIMURA H，SASAKI H，INAGAKI N，et al.Nine phenethyl alcohol glycosides from Stachys sieboldii[J].Phytochemistry，2001，30: 965-969.

[48]PEDERSEN J A.Distribution and taxonomic im plications of some phenolics in the family Lamiaceae determined by ESR spectroscopy [J].Biochemical Systematics and Ecology，2000，28:229-253.

[49]TADAHIRO T，YUJI N，NORIYASU H.Studies on the constituents of Leonotis nepetifolia[J].Chemical and Pharmaceutical Bulletin，1999，47:284-286.

[50]DE SARRO A，CECCHETTI V，F(xiàn)RAVOLINI V，et al.Effects of novel 6-des uoroquinolones and classic quinolones on pentylenetetrazole-induced seizures in mice.Antimicrob[J].Antimicrobial Agents and Chemotherapy，1999，43:1729-1736.

(責(zé)任編輯:李建忠，付強(qiáng)，張陽，羅敏；英文編輯:周序林，鄭玉才)

Progress in pharmacieticul research of Leonotis leonurus

WANG Xiao-ling，YUAN lv-yi
(School of Pharmacy，Southwest University for Nationalities，Chengdu 610041，P.R.C.)

Objective To summarize the botanical aspects，ethnopharmacology，phytochemistry，biological activity，toxicity and commercial aspects of L.leonurus.Methods An extensive review of the literature from 1900 to 2015 was carried out.Electronic databases including Scopus，Sci Finder，Pubmed，Google Scholar were used as data sources.All abstracts，full-text articles and books written in English were considered.Result L.leonurus contains mainly terpenoids，particularly labdane diterpenes.Other compounds reported by some authors have been isolated from the plant，including the mildly psychoactive alkaloid.Leonurine has however，never been reported in the extracts of L.leonurus.Conclusion Despite the publication of various papers on L.leonurus，there is still demand for definitive research and clarification of other compounds.Research has proven the psychoactive effects of the crude extract of L.leonurus，but confirmation of the presence of psychoactive compounds，as well as isolation and characterization，is still required.

Leonotis Leonurus；labdane diterpenes；pharmacological activities

R28；R29

A

2095-4271(2016)05-0484-08

10.11920/xnmdzk.2016.05.003

2016-07-25

王曉玲(1969—)，女，漢族，四川資陽人，教授，博士，研究方向:天然藥物化學(xué).E-mail:wxl3232＠sina.com

四川省科技廳科技支撐項目(2015SZ0040)