Figures (8)  Tables (3)
    • Figure 1. 

      (a) Whole plant, (b) medicinal portion, and (c) commercial herbal pieces of Lindera aggregata.

    • Figure 2. 

      General geographical distribution of Lindera aggregata in China.

    • Figure 3. 

      Structures of sesquiterpenoids (1−87) isolated from Lindera aggregata.

    • Figure 4. 

      Structures of alkaloids (88-125) isolated from Lindera aggregata.

    • Figure 5. 

      Structures of flavonoids (126−147) isolated from Lindera aggregata.

    • Figure 6. 

      Structures of cyclopentanedione derivatives and enantiomers of ketone derivatives (148−157) isolated from Lindera aggregata.

    • Figure 7. 

      Structures of disesquiterpenoid−geranylbenzofuranone conjugates, benzenoids and benzenoid glycosides and other compounds isolated from Lindera aggregata.

    • Figure 8. 

      The main biological activities and corresponding mechanisms of Lindera aggregata.

    • Preparation nameCompositionRole of LA in prescriptionTraditional and clinical usesReferences
      Suo Quan WanLindera aggregata, Alpinia oxyphylla, Dioscorea polystachyaLeading roleTreatment of nocturnal enuresis and frequent urination caused by kidney deficiencyWeishi Jiacangfang (《魏氏家藏方》)
      Tiantai Wuyao SanLindera aggregata, Aucklandia costus, Foeniculum vulgare, Citrus reticulata, Alpinia officinarum, Areca catechu, Melia azedarach, Croton tigliumLeading roleTreat small intestinal hernia, reduce abdominal pain and induce testiclesSheng Ji Zong Lu (《圣济总录》)
      Wu Yao TangLindera aggregata, Cyperus rotundus, Aucklandia costus, Angelica sinensis, Glycyrrhiza uralensisLeading roleTreatment of irregular menstruation, dysmenorrhea, premenstrual syndrome, chronic pelvic inflammatory disease, chronic hepatitis, hyperplasia of mammary glands, and chronic gastritisJi Yin Gangmu
      (《济阴纲目》)
      Wu Mo Yin ZiLindera aggregata, Aquilaria sinensis, Areca catechu, fruit of Citrus aurantium, Aucklandia costusLeading roleRelieve depression, treat anger and convulsionYifang Jijie
      (《医方集解》)
      Zheng Qi Tian Xiang SanLindera aggregata, Cyperus rotundus, Citrus reticulata, Perilla frutescens, Zingiber officinaleLeading roleTreat menstrual irregularities, chest and side painYixue Gangmu
      (《医学纲目》)
      Wu Yao SanLindera aggregata, Cyperus rotundus, Alpinia officinarum, Paeonia lactifloraLeading roleReconcile milk to treat children's night cryingTherapeutics of Children’s Disease (《小儿药证直诀》)
      Jia Wei Wu Yao TangLindera aggregata, Cyperus rotundus, Amomum villosum, Aucklandia costusLeading rolePromote blood circulation, regulate menstruation, and relieve painJi Yin Gangmu
      (《济阴纲目》)
      Bai He TangLilium brownii var. viridulum, Lindera aggregataSupporting roleTreatment of heartache and epigastric painShifang Kuoge
      (《时方歌括》)
      Bu Xin TangAngelica sinensis, Rehmannia glutinosa, Paeonia lactiflora, Corydalis yanhusuo, Lindera aggregata, Paeonia × suffruticosa, Polygala tenuifolia, (Poria cocos Schw.), Dimocarpus longanSupporting roleTreatment of heartache and limb chillsYu An (《玉案》)
      Si Mo TangPanax ginseng, Areca catechu, Aquilaria sinensis, Lindera aggregataSupporting roleTreatment of chest tightness and anorexiaJi Sheng Fang
      (《济生方》)
      Tong Yu JianAngelica sinensis, Carthamus tinctorius, Crataegus pinnatifida, Lindera aggregata, Citrus reticulata, Cyperus rotundus, Alisma plantago-aquaticaSupporting roleActivating blood circulation and removing blood stasis, promoting “Qi” and relieving painComplete Collection of Jingyue's Treatise (《景岳全书》)
      Nuan Gan JianAngelica sinensis, Lycium chinense, (Poria cocos Schw.), Foeniculum vulgare, Cinnamomum cassia, Lindera aggregata, Aquilaria sinensisSupporting roleTreat liver and kidney colds, abdominal pain, and herniaComplete Collection of Jingyue's Treatise (《景岳全书》)
      Ai Fu Nuan Gong WanAmbrosia artemisiifolia, Cyperus rotundus, Cinnamomum cassia, Angelica sinensis, Paeonia lactiflora Pall. Phlomoides umbrosa (Turcz.) Kamelin & Makhm., Lindera aggregata, Morinda officinalis, Kadsura heteroclitaSupporting roleTreatment of menstrual irregularity and dysmenorrheaShenshi Zhen Sheng Shu
      (《沈氏尊生书》)
      Liu Mo TangAquilaria sinensis, Aucklandia costus, Areca catechu, Lindera aggregata, fruit of Citrus aurantium, Rheum palmatumSupporting roleTreatment of bloating and constipationZhengzhi Zhunshen
      (《证治准绳》)

      Table 1. 

      Examples of traditional Chinese medicine prescriptions containing Lindera aggregata.

    • ClassCompoundsPart of the plantChromatographic methodsType of extractReference
      SesquiterpenesLinderaggredin A 1Whole plantsChromatography, 1H NMR spectrum, HSQC NMR spectral, HMBC spectral, NOESY spectraMethanol extractKuo et al.[25]
      Linderaggredin B 2Whole plantsChromatography, 1H NMR spectrum, HSQC NMR spectral, HMBC spectral, NOESY spectraMethanol extractKuo et al.[25]
      Linderaggredin C 3Whole plantsChromatography, 1H NMR spectrum, HSQC NMR spectral, HMBC spectral, NOESY spectraMethanol extractKuo et al.[25]
      Linderaggredin D 4Whole plantsChromatography, 1H NMR spectrum, HSQC NMR spectral, HMBC spectral, NOESY spectraMethanol extractKuo et al.[25]
      Linderanlide A 5RootsUV, IR, NMR, HR-ESI-MS, and CD spectra, CD spectral, CCEthanol extractQiang et al.[26]
      Linderanlide B 6RootsUV, IR, NMR, HR-ESI-MS, and CD spectra, CD spectral, CCEthanol extractQiang et al.[26]
      Linderanlide C 7RootsUV, IR, NMR, HR-ESI-MS, and CD spectra, CD spectral, CCEthanol extractQiang et al.[26]
      Linderanlide D 8RootsUV, IR, NMR, HR-ESI-MS, and CD spectra, CD spectral, CCEthanol extractQiang et al.[26]
      Linderanlide E 9RootsUV, IR, NMR, HR-ESI-MS, and CD spectra, CD spectral, CCEthanol extractQiang et al.[26]
      Linderanlide F 10RootsUV, IR, NMR, HR-ESI-MS, and CD spectra, CD spectral, CCEthanol extractQiang et al.[26]
      Sesquiterpenoids (6) 11RootsUV, IR, NMR, HR-ESI-MS, and CD spectra, CD spectralEthanol extractQiang et al.[26]
      Sesquiterpenoids (7) 12RootsUV, IR, NMR, HR-ESI-MS, and CD spectra, CD spectralEthanol extractQiang et al.[26]
      Sesquiterpenoids (8) 13RootsUV, IR, NMR, HR-ESI-MS, and CD spectra, CD spectralEthanol extractQiang et al.[26]
      Sesquiterpenoids (9) 14RootsUV, IR, NMR, HR-ESI-MS, and CD spectra, CD spectralEthanol extractQiang et al.[26]
      Sesquiterpenoids (10) 15RootsUV, IR, NMR, HR-ESI-MS, and CD spectra, CD spectralEthanol extractQiang et al.[26]
      Sesquiterpenoids (11) 16RootsUV, IR, NMR, HR-ESI-MS, and CD spectra, CD spectralEthanol extractQiang et al.[26]
      Sesquiterpenoids (13) 17RootsUV, IR, NMR, HR-ESI-MS, and CD spectra, CD spectralEthanol extractQiang et al.[26]
      Sesquiterpenoids (14) 18RootsUV, IR, NMR, HR-ESI-MS, and CD spectra, CD spectralEthanol extractQiang et al.[26]
      Sesquiterpenoids (15) 19RootsUV, IR, NMR, HR-ESI-MS, and CD spectra, CD spectralEthanol extractQiang et al.[26]
      Neolindenenonelactone 20RootsFast atom bom-bardment mass spectroscopy, one-dimensional nuclear magnetic resonance spectroscopy, two-dimensional-nuclear magnetic resonance spectroscopy, ilica gel column chromatography,TLCEtOH extractCheng et al.[27]
      Linderagalactones A 21RootsHRESIMS, 2D NMR, ECD spectra, HMBC spectrum, NOESY spectrum, silica gel GF254
      plates, C18 reversed-phase silica gel, TLC
      EtOH extractGan et al.[28]
      Linderagalactones B 22RootsHRESIMS, 2D NMR, ECD spectra, HMBC spectrum, NOESY spectrum, silica gel GF254
      plates, C18 reversed-phase silica gel, TLC
      EtOH extractGan et al.[28]
      Linderagalactones C 23RootsHRESIMS, 2D NMR, ECD spectra, HMBC spectrum, NOESY spectrum, silica gel GF254
      plates, C18 reversed-phase silica gel, TLC
      EtOH extractGan et al.[28]
      Linderagalactones D 24RootsHRESIMS, 2D NMR, ECD spectra, HMBC spectrum, NOESY spectrum, silica gel GF254
      plates, C18 reversed-phase silica gel, TLC
      EtOH extractGan et al.[28]
      Linderagalactones E 25RootsHRESIMS, 2D NMR, ECD spectra, HMBC spectrum, NOESY spectrum, silica gel GF254
      plates, C18 reversed-phase silica gel, TLC
      EtOH extractGan et al.[28]
      Linderanoid A 26RootsUV spectra, ECD spectra, NMR SpectrumEthanol extractLiu et al.[29]
      Linderanoid B 27RootsUV spectra, ECD spectra, NMR SpectrumEthanol extractLiu et al.[29]
      Linderanoid C 28RootsUV spectra, ECD spectra, NMR SpectrumEthanol extractLiu et al.[29]
      Linderanoid D 29RootsUV spectra, ECD spectra, NMR SpectrumEthanol extractLiu et al.[29]
      Linderanoid E 30RootsUV spectra, ECD spectra, NMR SpectrumEthanol extractLiu et al.[29]
      Linderanoid F 31RootsUV spectra, ECD spectra, NMR SpectrumEthanol extractLiu et al.[29]
      Linderanoid G 32RootsUV spectra, ECD spectra, NMR SpectrumEthanol extractLiu et al.[29]
      Linderanoid H 33RootsUV spectra, ECD spectra, NMR SpectrumEthanol extractLiu et al.[29]
      Linderanoid I 34RootsUV spectra, ECD spectra, NMR SpectrumEthanol extractLiu et al.[29]
      Linderanoid J 35RootsUV spectra, ECD spectra, NMR SpectrumEthanol extractLiu et al.[29]
      Linderanoid K 36RootsUV spectra, ECD spectra, NMR SpectrumEthanol extractLiu et al.[29]
      Linderanoid L 37RootsUV spectra, ECD spectra, NMR SpectrumEthanol extractLiu et al.[29]
      Linderanoid M 38RootsUV spectra, ECD spectra, NMR SpectrumEthanol extractLiu et al.[29]
      Linderanoid N 39RootsUV spectra, ECD spectra, NMR SpectrumEthanol extractLiu et al.[29]
      Linderanoid O 40RootsUV spectra, ECD spectra, NMR SpectrumEthanol extractLiu et al.[29]
      Linderaggrenolide A 41RootsNMR spectra, UV spectra, ECD spectra, HRESIMS, Silica gel column chromatography,
      thin layer chromatography
      EtOH extractLiu et al.[30]
      LinderaggrenolideB 42RootsNMR spectra, UV spectra, ECD spectra, HRESIMS, Silica gel column chromatography,
      thin layer chromatography
      EtOH extractLiu et al.[30]
      Linderaggrenolide C 43RootsNMR spectra, UV spectra, ECD spectra, HRESIMS, Silica gel column chromatography,
      thin layer chromatography
      EtOH extractLiu et al.[30]
      Linderaggrenolide D 44RootsNMR spectra, UV spectra, ECD spectra, HRESIMS, Silica gel column chromatography,
      thin layer chromatography
      EtOH extractLiu et al.[30]
      Linderaggrenolide E 45RootsNMR spectra, UV spectra, ECD spectra, HRESIMS, Silica gel column chromatography,
      thin layer chromatography
      EtOH extractLiu et al.[30]
      Linderaggrenolide F 46RootsNMR spectra, UV spectra, ECD spectra, HRESIMS, Silica gel column chromatography,
      thin layer chromatography
      EtOH extractLiu et al.[30]
      Linderaggrenolide G 47RootsNMR spectra, UV spectra, ECD spectra, HRESIMS, Silica gel column chromatography,
      thin layer chromatography
      EtOH extractLiu et al.[30]
      Linderaggrenolide H 48RootsNMR spectra, UV spectra, ECD spectra, HRESIMS, Silica gel column chromatography,
      thin layer chromatography
      EtOH extractLiu et al.[30]
      Linderaggrenolide I 49RootsNMR spectra, UV spectra, ECD spectra, HRESIMS, Silica gel column chromatography,
      thin layer chromatography
      EtOH extractLiu et al.[30]
      Linderaggrenolide J 50RootsNMR spectra, UV spectra, ECD spectra, HRESIMS, Silica gel column chromatography,
      thin layer chromatography
      EtOH extractLiu et al.[30]
      Linderaggrenolide K 51rootsNMR spectra, UV spectra, ECD spectra, HRESIMS, Silica gel column chromatography,
      thin layer chromatography
      EtOH extractLiu et al.[30]
      Linderaggrenolide L 52rootsNMR spectra, UV spectra, ECD spectra, HRESIMS, Silica gel column chromatography,
      thin layer chromatography
      EtOH extractLiu et al.[30]
      Linderaggrenolide N 53rootsNMR spectra, UV spectra, ECD spectra, HRESIMS, Silica gel column chromatography,
      thin layer chromatography
      EtOH extractLiu et al.[30]
      Linderaggrenolide N 54rootsNMR spectra, UV spectra, ECD spectra, HRESIMS, Silica gel column chromatography,
      thin layer chromatography
      EtOH extractLiu et al.[30]
      Aggreganoid A 55\IR spectrum, NMR spectra, ECD spectraEtOH extractLiu et al.[31]
      Aggreganoid B 56\NMR spectraEtOH extractLiu et al.[31]
      Aggreganoid C 57\positive HR-ESIMS spectrum, NMR spectra, ECD spectraEtOH extractLiu et al.[31]
      Aggreganoid D 58\NMR spectraEtOH extractLiu et al.[31]
      Aggreganoid E 59\NMR spectraEtOH extractLiu et al.[31]
      Aggreganoid F 60\NMR spectraEtOH extractLiu et al.[31]
      Linderolide G 61RootsUV spectra, IR spectra, CD spectra, NMR spectra, EI-mass spectra, CC, TLCMethanol extractLiu et al.[32]
      Linderolide H 62RootsUV spectra, IR spectra, CD spectra, NMR spectra, EI-mass spectra, CC, TLCMethanol extractLiu et al.[32]
      Linderolide I 63RootsUV spectra, IR spectra, CD spectra, NMR spectra, EI-mass spectra, CC, TLCMethanol extractLiu et al.[32]
      Linderolide J 64RootsUV spectra, IR spectra, CD spectra, NMR spectra, EI-mass spectra, CC, TLCMethanol extractLiu et al.[32]
      Linderolide K 65RootsUV spectra, IR spectra, CD spectra, NMR spectra, EI-mass spectra, CC, TLCMethanol extractLiu et al.[32]
      Linderolide L 66RootsUV spectra, IR spectra, CD spectra, NMR spectra, EI-mass spectra, CC, TLCMethanol extractLiu et al.[32]
      Linderolide M 67RootsUV spectra, IR spectra, CD spectra, NMR spectra, EI-mass spectra, CC, TLCMethanol extractLiu et al.[32]
      Lindestrenolide 68RootsUV spectra, IR spectra, CD spectra, NMR spectra, EI-mass spectra, CC, TLCMethanol extractLiu et al.[32]
      Shizukanolide 69RootsUV spectra, IR spectra, CD spectra, NMR spectra, EI-mass spectra, CC, TLCMethanol extractLiu et al.[32]
      Chloranthalactone D 70RootsUV spectra, IR spectra, CD spectra, NMR spectra, EI-mass spectra, CC, TLCMethanol extractLiu et al.[32]
      Lindenene 71RootsUV spectra, IR spectra, CD spectra, NMR spectra, EI-mass spectra, CC, TLCMethanol extractLiu et al.[32]
      Lindenenol 72RootsUV spectra, IR spectra, CD spectra, NMR spectra, EI-mass spectra, CC, TLCMethanol extractLiu et al.[32]
      Lindenonolide H 73RootsUV spectra, IR spectra, CD spectra, NMR spectra, EI-mass spectra, CC, TLCMethanol extractLiu et al.[32]
      Lindenanolide A 74RootsUV spectra, IR spectra, CD spectra, NMR spectra, EI-mass spectra, CC, TLCMethanol extractLiu et al.[32]
      Lindestrene 75RootsUV spectra, IR spectra, CD spectra, NMR spectra, EI-mass spectra, CC, TLCMethanol extractLiu et al.[32]
      8-hydroxyisogermafurenolide 76RootsUV spectra, IR spectra, CD spectra, NMR spectra, EI-mass spectra, CC, TLCMethanol extractLiu et al.[32]
      Linderane 77RootsUV spectra, IR spectra, CD spectra, NMR spectra, EI-mass spectra, CC, TLCMethanol extractLiu et al.[32]
      Dehydrolindestrenolide II 78LeavesNMR spectra, TLC, Silica gel column chromatographyEthanol extractZhang et al.[33]
      Hydroxylinderstrenolide III 79LeavesNMR spectra, TLC, Silica gel column chromatographyEthanol extractZhang et al.[33]
      Linderalactone IV 80LeavesNMR spectra, TLC, Silica gel column chromatographyEthanol extractZhang et al.[33]
      6-acetyl lindenanolide B-1 I 81LeavesNMR spectra, TLC, Silica gel column chromatographyEthanol extractZhang et al.[33]
      6-acetyl lindenanolide B-2 I 82LeavesNMR spectra, TLC, Silica gel column chromatographyEthanol extractZhang et al.[33]
      Lindenanolide H (2) 83LeavesTLC, HPLC, NMR spectraEthanol extractSun et al.[34]
      Lindenanolide A (3) 84LeavesTLC, HPLC, NMR spectraEthanol extractSun et al.[34]
      Atractylenolide III(4) 85LeavesTLC, HPLC, NMR spectraEthanol extractSun et al.[34]
      Linderin A 86RootsIR spectra, NMR spectra, HR-ESI-MS, Thin-layer chromatography, silica gel G
      precoated plates
      Ethanol extractWen et al.[35]
      Linderin B 87RootsIR spectra, NMR spectra, HR-ESI-MS, Thin-layer chromatography, silica gel G
      precoated plates
      Ethanol extractWen et al.[35]
      AlkaloidLinderaggrine B 88Whole plantsChromatography, 1H NMR spectrum, NOESY spectraMethanol extractKuo et al.[25]
      (1′S)-12′-hydroxyl-linderegatine 89RootsUV spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      (1S)-5′-O-p-hydroxybenzoyl norreticuline 90RootsUV spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      (1R, 1′R)-11,11′-biscoclaurine 91RootsUV spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      Costaricine 92RootsUV spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      N-methyllauro-tetanine 93RootsUV, spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      Laurotetanine 94RootsUV, spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      Actinodaphnine 95RootsUV, spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      Isoboldine 96RootsUV, spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      Laurolitsine 97RootsUV, spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      Norisoboldine 98RootsUV, spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      Boldine 99RootsUV, spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      Norjuziphine 100RootsUV, spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      Reticuline 101RootsUV spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      Reticuline n-oxide 102RootsUV spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      Boldine n-oxide 103RootsUV spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      N-methyllaurotetanine n-oxide 104RootsUV spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      Salutaridinen-oxide 105RootsUV spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      Linderegatine 106RootsUV spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      Lindoldhamine 107RootsUV spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      Secolaurolitsine 108RootsUV spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      Secoboldine 109RootsUV spectra, HRESIMS spectra, Waters HPLC column, NMR spectroscopy, ECD spectra,
      Thin-layer chromatography, Silica gel column chromatography
      EtOH extractYang et al.[36]
      (+)-norboldine acetate 110Roots2D NMR spectra, 1H NMR spectra, IR spectra, NMR spectra, RP-18 columnEtOH extractGan et al.[37]
      (+)-norboldine 111Roots2D NMR spectra, 1H NMR spectra, IR spectra, NMR spectra, Silica gel column chromatographyEtOH extractGan et al.[37]
      (+)-boldine 112Roots2D NMR spectra, IR spectra, NMR spectra, RP-18 columnEtOH extractGan et al.[37]
      (+)-laurotetanine 113Roots2D NMR spectra, IR spectra, NMR spectra, Silica gel column chromatographyEtOH extractGan et al.[37]
      (+)-N-methyllaurotetanine114Roots2D NMR spectra, IR spectra, NMR spectra, Silica gel column chromatographyEtOH extractGan et al.[37]
      (+)-reticuline 115Roots2D NMR spectra, IR spectra, NMR spectra, Silica gel column chromatographyEtOH extractGan et al.[37]
      (−)-pronuciferine 116Roots2D NMR spectra, IR spectra, NMR spectra, Silica gel column chromatographyEtOH extractGan et al.[37]
      Pallidine 117Roots2D NMR spectra, IR spectra, NMR spectra, RP-18 columnEtOH extractGan et al.[37]
      Demethylcoclaurine-7-o- glucoside 118Roots\Methanol extractPeng et al.[38]
      Coclaurine 119Roots\Methanol extractPeng et al.[38]
      Magnocurarine 120Roots\Methanol extractPeng et al.[38]
      Boldine 121Roots\Methanol extractPeng et al.[38]
      Reticuline 122Roots\Methanol extractPeng et al.[38]
      Hernangerine 123Roots\Methanol extractPeng et al.[38]
      N-methyllaurotetanine124Roots\Methanol extractPeng et al.[38]
      Karakoramine 125Roots\Methanol extractPeng et al.[38]
      FlavonoidsQuercetin 126LeavesInfrared spectrum, NMR spectra, TLCEthanol extractZhang et al.[39]
      Quercetin-3-O-rhamnoside 127LeavesInfrared spectrum, NMR spectra, TLCEthanol extractZhang et al.[39]
      Kampferol-3-O-L-arabinopyranoside 128LeavesInfrared spectrum, NMR spectra, TLCEthanol extractZhang et al.[39]
      Quercetin-3-O-β-D-galactopyranoside 129LeavesInfrared spectrum, NMR spectra, TLCEthanol extractZhang et al.[39]
      Isorhamnetin-3-O-[β-D-glucopyranosy-l (6→1)- rhamno-side]130LeavesInfrared spectrum, NMR spectra, TLCEthanol extractZhang et al.[39]
      Kampferol-3-O-α-glicurinoside 131LeavesInfrared spectrum, NMR spectra, TLCEthanol extractZhang et al.[39]
      Nubigenol 132LeavesInfrared spectrum, NMR spectra, TLCEthanol extractZhang et al.[40]
      Kaempferol-3-O-(6″-trans-p-coumaroyl)-β-D-glucopyranoside 133LeavesInfrared spectrum, NMR spectra, TLCEthanol extractZhang et al.[40]
      Chrysoeriol-7-β-D-glucopyranoside 134LeavesInfrared spectrum, NMR spectra, TLCEthanol extractZhang et al.[40]
      Rutin 135LeavesInfrared spectrum, NMR spectra, TLCEthanol extractZhang et al.[40]
      Kaempferol-3-O-L-rhamnoside 136LeavesNMR spectra, TLCEthanol extractXiao et al.[41]
      Kaempferol 137LeavesNMR spectra, TLCEthanol extractXiao et al.[41]
      Dihydrokaempferol-3-O-L-rhamnoside 138LeavesNMR spectra, TLCEthanol extractXiao et al.[41]
      Quercetin 139LeavesNMR spectra, TLCEthanol extractXiao et al.[41]
      Kaempferol-3-O-D-glucopyranoside 140LeavesNMR spectra, TLCEthanol extractXiao et al.[41]
      Avicularin 141LeavesNMR spectra, TLCEthanol extractLuo et al.[42]
      Afzelin 142LeavesNMR spectra, TLCEthanol extractLuo et al.[42]
      Dihydrokaempferol 143LeavesNMR spectra, TLCEthanol extractLuo et al.[42]
      Astragaline 144LeavesNMR spectra, TLCEthanol extractLuo et al.[42]
      Kaempfero-l3-O-β-D-xylopyranoside 145LeavesNMR spectra, TLCEthanol extractLuo et al.[42]
      Juglalin 146leavesNMR spectra, TLCEthanol extractLuo et al.[42]
      Kaempfero-l3-O-(2″-O-β-D-glucopyranosyl)-α-L-rhamnopyranoside 147leavesNMR spectra, TLCEthanol extractLuo et al.[42]
      Cyclopentenedione derivatives(±)-lindepentone A 148RootsNMR spectra, ESIMS, HRESIMS, Silica gel column chromatography, High performance liquid chromatographyEtOAc extractChen et al.[45]
      Lindoxepine A 149RootsNMR spectra, ESIMS, HRESIMS, Silica gel column chromatography, High performance liquid chromatographyEtOAc extractChen et al.[45]
      Lindoxepine B 150RootsNMR spectra, ESIMS, HRESIMS, Silica gel column chromatography, High performance liquid chromatographyEtOAc extractChen et al.[45]
      Epi-bi-linderone 151RootsNMR spectra, ESIMS, HRESIMS, Silica gel column chromatography, High performance liquid chromatographyEtOAc extractChen et al.[45]
      Bi-linderone 152RootsNMR spectra, ESIMS, HRESIMS, Silica gel column chromatography, High performance liquid chromatographyEtOAc extractChen et al.[45]
      Linderaspirone A 153RootsNMR spectra, ESIMS, HRESIMS, Silica gel column chromatography, High performance liquid chromatographyEtOAc extractChen et al.[45]
      Methyllinderone 154RootsNMR spectra, ESIMS, HRESIMS, Silica gel column chromatography, High performance liquid chromatographyEtOAc extractChen et al.[45]
      Methyllucidone (a pair of cis–trans isomers, 9a and 9b) 155RootsNMR spectra, ESIMS, HRESIMS, Silica gel column chromatography, High performance liquid chromatographyEtOAc extractChen et al.[45]
      Enantiomers of ketone derivatives(+)-demethoxy-epi-bi-linderone (4a) 156RootsNMR spectra, ESIMS, HRESIMS,Silica gel column chromatography, High performance liquid chromatographyEtOAc extractChen et al.[45]
      (-)-demethoxy-epi-bi-linderone (4b) 157RootsNMR spectra, ESIMS, HRESIMS,Silica gel column chromatography, High performance liquid chromatographyEtOAc extractChen et al.[45]
      Disesquiterpenoid−geranylbenzofuranone conjugatesLinderalide A 158RootsUV spectra, CD spectra, NMR spectra, Waters XBridge C18 (5 μm, 250 × 10 mm2, i.d.) columns, Siliabond C18 ODS column, Silica gel column chromatographyEhanol extractLiu et al.[46]
      Linderalide B 159RootsUV spectra, CD spectra, NMR spectra, Waters XBridge C18 (5 μm, 250 ×10 mm2, i.d.) columns, Siliabond C18 ODS column, Silica gel column chromatographyEhanol extractLiu et al.[46]
      Linderalide C 160RootsUV spectra, CD spectra, NMR spectra, Waters XBridge C18 (5 μm, 250 ×10 mm2, i.d.) columns, Siliabond C18 ODS column, Silica gel column chromatographyEhanol extractLiu et al.[46]
      Linderalide D 161RootsUV spectra, CD spectra, NMR spectra, Waters XBridge C18 (5 μm, 250 ×10 mm2, i.d.) columns, Siliabond C18 ODS column, Silica gel column chromatographyEhanol extractLiu et al.[46]
      Benzenoids andlinderagatin A 162Roots1D (1H, 13C) spectra, 2D NMR (COSY, NOESY, HSQC and HMBC) spectra, ECD spectra, CC, TLCMeOH extractsMa et al.[47]
      linderagatin B (1-2) 163Roots1D (1H, 13C) spectra, 2D NMR (COSY, NOESY, HSQC and HMBC) spectra, ECD spectra, CC, TLCMeOH extractsMa et al.[47]
      benzenoid glycoside6′-O-vanilloyl-5-hydroxy-2,3-dimethoxyphenol 1-O-β-D-gluco-pyranoside 164Whole plantsChromatography, 1H NMR spectrum, HMBC spectral, HSQC NMR spectralMethanol extractKuo et al.[25]
      Others9,9′-dihydroxy-3,4-methylenedioxy-3′-methoxy [7-O-4′,8-5′]Lignans 165LeavesTLC, HPLC, NMR spectraEthanol extractSun et al.[34]
      Hernangerine 166RootsTLC, NMR spectraEthanol extractZhu et al.[48]
      ‘\’ Denotes no useful information found in the study.

      Table 2. 

      The main compounds isolated from Lindera aggregata.

    • Pharmacological activityTested substanceModelTested living system/ organ/cellResultDose rangeTime period of applicationReferences
      Anti-inflammatory activityEthanol extractC57BL/6 miceColonic tissueRegulated the IL-6 signaling pathway to modulate the balance of Th17 and Treg cells, thus attenuated DSS-induced colitis in mice1–1.7 g/kg21 dLai et al.[49]
      Ethanol extractSD ratsFeces and serumExerted anti-UC effects on the rat model induced by TNBS and that the mechanism might be associated with the inhibition of inflammatory cytokines, such as IL-6 and TNF-α0.5, 1, 2 g /kg9 dLai et al.[50]
      \C57BL/6 miceColonic tissuePromoted Treg differentiation and attenuates colitis via targeting glycolysis and subsequent NAD+/SIRT1/SUV39H1/H3K9me3 signaling pathway40 mg/kg10 dQi et al.[51]
      Ethanol extractICR micePawExhibited a potential therapeutic effect on CIA in mice as the main active constituent of LA responsible for the benefits for RA remedy10, 20, 40 mg/kg20 dLuo et al.[52]
      \SD ratsCellBeen able to prevent IL-1b-induced release of IL-6 from rat FLS, key producers of IL-6 in synovial membranes of joints3, 10, 30, 60 mM14 dWei et al.[53]
      \ICR miceCellSuppressed osteoclast differentiation through Preventing the accumulation of TRAF6-TAK1 complexes and activation of MAPKs/NF-kB/c-Fos/NFATc1 Pathways3, 10, 30 mM5 dWei et al.[54]
      \Wistar ratsPawAttenuated osteoclast differentiation and Inflammatory bone Erosion in an aryl hydrocarbon receptor-Dependent Manner15 mg/kg14 dWei et al.[55]
      \Wistar ratsPawAmeliorated collagen-induced arthritis through regulating the balance between Th17 and regulatory T cells in gut-associated lymphoid tissues15, 30 mg/kg14 dTong et al.[56]
      Ethanol extractSD ratsPawHad obvious therapeutic effect on adjuvant arthritis in rats200, 100, 50 mg/kg11 dLiu et al.[57]
      \Sprague – Dawley ratsSynovial tissueReduced the number of blood vessels and the expression of growth factors in the synovium of AA rats, inhibited VEGF-induced in vitro angiogenesis in HUVECs\10 dLu et al.[58]
      Hepatoprotective effectWYSTW (water extract)SD ratsSerum and liver tissueSuppressed NF-κB, TNF- α expression, reducing IL-1β2 g/kg10 dWang et al.[59]
      WYCTW (ethanol extract)SD ratsSerum and liver tissueSignificantly reduced serum ALT content and serum AST content, suppressed NF-κB, TNF-α expression, reducing IL-1β2 g/kg10 dWang et al.[59]
      WYCTC1 (alcohol extract petroleum ether extract)SD ratsSerum and liver tissueSignificantly reduced serum ALT content and serum AST content, suppressed NF-κB, TNF-α expression, reducing IL-1β2 g/kg10 dWang et al.[59]
      WYCTC2 (ethyl acetate extract of LA alcohol extract)SD ratsSerum and liver tissueSignificantly reduced serum ALT content and serum AST content, suppressed NF-κB, TNF-α expression, reducing IL-1β2 g/kg10 dWang et al.[59]
      WYCTC3 (alcohol extract n-butanol extract)SD ratsSerum and liver tissueSignificantly reduced serum ALT content and serum AST content, suppressed NF-κB, TNF-α expression, reducing IL-1β2 g/kg10 dWang et al.[59]
      WYCTC4 (alcohol extract water extract)SD ratsSerum and liver tissueSignificantly reduced serum ALT content and serum AST content, suppressed NF-κB, TNF-α expression, reducing IL-1β2 g/kg10 dWang et al.[59]
      Water extractSD ratsLiver tissue and bloodHad preventive effect on alcoholic liver injury by inhibiting serum ACT and AST levels, and this beneficial effect might be associated with anti-inflammation and anti-oxidation1 ml/100 g10 dWang et al.[62]
      Ethanol extractSD ratsLiver tissue and bloodHad preventive effect on alcoholic liver injury by inhibiting serum ACT and AST levels, and this beneficial effect may be associated with anti-inflammation and anti-oxidation1 ml/100 g10/dWang et al.[62]
      WYSTWSD ratsSerum and small intestine tissueHad the effect of protecting liver4 g/kg33 dJi et al.[63]
      WYCTWSD ratsSerum and small intestine tissueHad the effect of protecting liver4 g/kg33 dJi et al.[63]
      WYCTC1 (alcohol extract petroleum ether extract)SD ratsSerum and small intestine tissueHad the effect of protecting liver4 g/kg33 dJi et al.[63]
      WYCTC2 (ethyl acetate extract of LA alcohol extract)SD ratsSerum and small intestine tissueHad the effect of protecting liver4 g/kg33 dJi et al.[63]
      WYCTC3 (alcohol extract n-butanol extract)SD ratsSerum and small intestine tissueHad the effect of protecting liver4 g/kg33 dJi et al.[63]
      Ethanol extractRAW 264.7 cellsCellInhibitory activities on nitric oxide production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells,
      with IC50 values of 37.8 and 38.7 μM, respectively
      5, 10, 20, 40, 50 μM/ml26 hYang et al.[36]
      WYSTWSD ratsSerum and liver tissueIncreased serum SOD activity, decreased the expression of CYP2E1 mRNA2 g/kg10 dTang et al.[60]
      WYCTWSD ratsSerum and liver tissueIncreased serum SOD activity, decreased the expression of CYP2E1 mRNA2 g/kg10 dTang et al.[60]
      WYCTC1SD ratsSerum and liver tissueIncreased serum SOD activity, decreased the expression of CYP2E1 mRNA2 g/kg10 dTang et al.[60]
      WYCTC2SD ratsSerum and liver tissueIncreased serum SOD activity, decreased the expression of CYP2E1 mRNA2 g/kg10 dTang et al.[60]
      WYCTC3SD ratsSerum and liver tissueIncreased serum SOD activity, decreased the expression of CYP2E1 mRNA2 g/kg10 dTang et al.[60]
      WYCTC4SD ratsSerum and liver tissueIncreased serum SOD activity, decreased the expression of CYP2E1 mRNA2 g/kg10 dTang et al.[60]
      Ethanol extractSD ratsSerum and liver tissueBetter reduced the content of serum MDA, increased the activity of SOD in serum and liver tissue, and reduced the expression of CYP2E1 mRNA in rats with acute alcoholic liver injury1 ml/100 g10 dChen et al.[61]
      Ethanol extractICR miceSerum and liver tissueReduced the serum transaminase activity and the production of lipid peroxidation intermediate MDA in CCl4 liver injured mice, and significantly enhanced the TAOC and SOD activities50, 100, 200 mg/kg7 dGu et al.[64]
      Ethanol extractHuman umbilical vein endothelial cells (HUVEcs)CellImproved the ability of endogenous antioxidation62.5, 125, 250, 500 µM5 hHan et al.[44]
      \SD ratsSerum and liver tissueIncreased the activity of SOD and GSH Px in serum of model rats and reduced the content of MDA, improved the antioxidant capacity against the liver injury induced by CCl4 in rats5, 15, 45 mg/kg6 weeksChen et al.[65]
      Anti-tumor activityEthanol extractHuman colon carcinoma cell line HCT-116CellCytotoxic activities against human colon carcinoma cell line (HCT-116), with IC50 values of 51.4 and 27.1 μM, respectively2.5, 5, 10, 20, 40, 50, 80, 100 μM/ml24~25 hYang et al.[66]
      Ethanol extractHuman colon carcinoma cell line HCT-116CellThe inhibition of cell proliferation in HCT116 occurred via induction of apoptosis and arrested of the G2/M and S cell
      cycle phases
      \\Yang et al.[66]
      Volatile oil extractA549, Eca-109and so onCellLeaf essential oil exhibited significant cytotoxicity against all the cells tested with a potential selectivity for cancerous cells12.5~400 μg/mL28 hYan et al.[68]
      Volatile oil extractHepG2CellInhibited HepG2 cell proliferation and induced HepG2 cell apoptosis50, 100, 150, 200 μg/mL8 hYan et al.[67]
      Volatile oil extractA549CellInhibited cell proliferation6.25, 12.5, 25, 50, 100, 200, 400 μg/ml4 hYan et al.[70]
      Volatile oil extractBel7402CellInhibited cell proliferation6.25, 12.5, 25, 50, 100, 200, 400 μg/ml4 hYan et al.[70]
      Volatile oil extractEca-109CellInhibited cell proliferation6.25, 12.5, 25, 50, 100, 200, 400 μg/ml4 hYan et al.[70]
      Volatile oil extractHeLaCellInhibited cell proliferation6.25, 12.5, 25, 50, 100, 200, 400 μg/ml4 hYan et al.[70]
      Volatile oil extractHT29CellInhibited cell proliferation6.25, 12.5, 25, 50, 100, 200, 400 μg/ml4 hYan et al.[70]
      Volatile oil extractMDA-MB-231CellInhibited cell proliferation6.25, 12.5, 25, 50, 100, 200, 400 μg/ml4 hYan et al.[70]
      Volatile oil extractPC-3CellInhibited cell proliferation6.25, 12.5, 25, 50, 100, 200, 400 μg/ml4 hYan et al.[70]
      Volatile oil extractSGC-7901CellInhibited cell proliferation6.25, 12.5, 25, 50, 100, 200, 400 μg/ml4 hYan et al.[70]
      Volatile oil extractSW1990CellInhibited cell proliferation6.25, 12.5, 25, 50, 100, 200, 400 μg/ml4 hYan et al.[70]
      Volatile oil extractU-2 OSCellInhibited cell proliferation6.25, 12.5, 25, 50, 100, 200, 400 μg/ml4 hYan et al.[70]
      \SGC-7901CellInduced the apoptosis of SGC-7901 by regulating the expression of p53, Bax, Bcl-2 and other key proteins0, 160, 200, 240 μmol/L24 hLiang et al.[69]
      \BALB/c nude miceTumor tissuesRegulated the BCL-2/caspase-3/PARP pathway and suppressed tumor growth in a human glioblastoma multiforme xenograft mouse model1, 2.5, 5 mg/kg,14 dHwang et al.[71]
      \Human A549 lung cancer cellsCellInhibited the invasion and migration of the A549 cancer cells and exhibited a dose-response association.1, 5, 10, 20 µM24 hChuang et al.[72]
      \The human OC cell lines SKOV-3 and OVCAR-3CellDecreased phophorylation of serine 727 and tyrosine 705 of STAT3 and expression of survivin, a STAT3-regulated gene0, 5, 10, 20, 50 µM48 hRajina et al.[73]
      Anti-hyperlipidemic effectWater extractSD ratsSerum and liver tissueHad lipid-lowering effect on hyperlipidemia model of rats1, 3, 9 g/kg6 weeksChen et al.[75]
      Water extractSD ratsSerum and renal tissueSignificantly promoted the reduction of TG, TC and LDL-C in rats fed with high-fat diet0.33, 0.66, 2.00 g/kg·bw45 dChen et al.[76]
      Water extractICR miceSerum and liver tissueHad the effect of lowering blood lipid, improved the steatosis
      of liver cells, and had a good therapeutic effect on fatty liver
      50, 100, 200 mg/kg4 weeksCao et al.[77]
      Water extractICR miceSerumAqLA-L treatment regulated the disorders of the serum lipid and liver function, reduced hepatic GLU contents both in normal and HCL mice0.3, 0.6, 1.2 g/kg10 dWang et al.[78]
      \SD ratsSerum and liver tissueReduced serum lipid level, improved liver cell lipid accumulation, and increased AMPK α Protein phosphorylation level, activating AMPK α to promote lipid metabolism1.6, 0.8 g/kg8 weeksSun et al.[79]
      Water extractrats of SPFSerum and liver tissueHad significant improving effect on changes in pathology of the liver tissues in rat models with hyperlipidemia. Its mechanism is probably realized by blocking TLR- 4/NF- κB signaling pathway, and reducing protein expression of TNF-α and IL-21.6, 0.8 g/kg8 weeksHan et al.[80]
      Antibacterial
      activity
      Polyphenol water extractStaphylococcus aureusDiameter of bacteriostatic ringSignificantly inhibited the growth of Staphylococcus aureus2.5 mg/mL24 hShen et al.[81]
      \H.pyloriBcterial growthIhibited he growth of H.pylori2, 4, 8, 16, 32, 64, 128 μg/mL\Tan et al.[74]
      Analgesic effectWater extractSD ratsSerumInhibited the serum MTL level of IBS-D rats and increased serum Sec level0.94, 1.88, 3.76 g/kg14 dXiao et al.[83]
      Ethanol extractZebrafish modelTotal motion distanceHad analgesic effect100 μg/mL1 hPeng et al.[38]
      Renal protectionEthanol extractSD ratsRenal tissueMitigated adenine-induced CKD by modulating the metabolic profile and TGF-β/Smad signaling pathway150 mg/kg14 dCai et al.[85]
      Water extractSD ratsRenal tissueMitigated adenine-induced CKD by modulating the metabolic profile and TGF-β/Smad signaling pathway150 mg/kg14 dCai et al.[85]
      Inhibition is emptying effectAqueous extractSD ratsPlasmaSuppressed gastric emptying rate, increased the content of cAMP, reduced the content of cGMP, increased the ratio of cAMP / cGMP10 mL/kg20 minNie et al.[86]
      Volatile oil extractSD ratsPlasmaSuppressed gastric emptying rate, increased the content of cAMP, reduced the content of cGMP, increased the ratio of cAMP / cGMP10 mL/kg20 minNie et al.[86]
      Ethanol extractSD ratsPlasmaReduce the content of cGMP10 mL/kg20 minNie et al.[86]
      Ether extractSD ratsPlasma\10 mL/kg20 minNie et al.[86]
      Ethanol-extraction ether extractSD ratsPlasmaSuppressed gastric emptying rate, increased the ratio of
      cAMP/cGMP
      10 mL/kg20 minNie et al.[86]
      Intestinal microbial regulation\SD ratsBlood and faecesImproved the species diversity of intestinal flora in rats, increased the stability of bacterial community structure, and regulated intestinal microorganisms in rats with alcoholic liver injury3, 2, 1 g/kg20 dXu et al.[87]
      Antidepressant effectWater extractC57/BL6 miceBloodReduced the serum level of corticosterone and expression of caspase-3, while increased expression of BDNF in vivo and increased cell viability in corticosterone treated PC12 cells, which was accompanied by decreased caspase-3 expression and the ratio of Bax/Bcl-2 mRNA expression as well as increased BDNF expression in vitro.30, 100, 300 mg/kg2 weeksChoi et al.[88]

      Table 3. 

      Pharmacological activities of Lindera aggregata.