Avanços na pesquisa dos efeitos farmacológicos e desenvolvimento de formulações da geniposídeo

  • role: First author第一作者
  • Affiliation:

    Key Laboratory of Modern Preparation of Traditional Chinese Medicine(TCM), Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004,China

    National Key Laboratory of Modern TCM Creation, Nanchang 330004,China

  • Email:guanym2008@163.com
  • Introduction:E-mailguanym2008@163.com
GUAN Yongmei12,  
  • Affiliation:

    Key Laboratory of Modern Preparation of Traditional Chinese Medicine(TCM), Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004,China

LIU Yidan1,  
  • Affiliation:

    School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang 330004,China

ZHANG Hua3,  
  • Affiliation:

    Key Laboratory of Modern Preparation of Traditional Chinese Medicine(TCM), Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004,China

ZHANG Haiyan1,  
  • role: Corresponding author通信作者
  • Affiliation:

    Key Laboratory of Modern Preparation of Traditional Chinese Medicine(TCM), Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004,China

  • Email:zangzhenzhongvip@163.com
  • Introduction:E-mailzangzhenzhongvip@163.com
ZANG Zhenzhong1*

Resumo

A geniposídeo é o principal componente ativo da medicina tradicional chinesa Gardenia, pertencente à classe dos glicosídeos éter cíclicos solúveis em água. Estudos farmacológicos demonstram que a geniposídeo possui várias atividades biológicas, incluindo proteção hepática, ação anti-inflamatória e analgésica, neuroproteção, efeito antidepressivo e inibição de danos por isquemia-reperfusão. Nos últimos anos, pesquisas revelaram que a geniposídeo também apresenta grande potencial na prevenção e tratamento de doenças como aterosclerose e osteoporose, mostrando amplas perspectivas de aplicação. Diversos experimentos in vivo e in vitro indicam que o mecanismo de ação da geniposídeo está principalmente relacionado à inibição das respostas inflamatórias, estresse oxidativo, melhora do metabolismo lipídico e regulação da apoptose celular. Devido à sua alta solubilidade em água e rápido metabolismo no organismo, sua biodisponibilidade oral é baixa, limitando sua eficácia farmacológica e aplicação clínica. Recentemente, para resolver o problema da biodisponibilidade da geniposídeo, foram desenvolvidas formulações como cremes, líquides cristalinos cúbicos, hidrogel e lipossomas. Este artigo revisa as pesquisas dos últimos 10 anos sobre a atividade farmacológica e o desenvolvimento de formulações da geniposídeo, baseando-se em literatura nacional e internacional, com o objetivo de fornecer fundamentos teóricos para futuras pesquisas e desenvolvimento da geniposídeo e suas formulações.

Palavras-chave

geniposídeo; proteção hepática; anti-inflamatório e analgésico; neuroproteção; formulações

References

  1. 1.
    LIU L P,WU Q,CHEN Y P,et al.Updated pharmacological effects,molecular mechanisms,and therapeutic potential of natural product geniposide[J].Molecules,2022,27(10):3319.
  2. 2.
    XU C K,ZHANG C B,YANG J P,et al.Textual research on gardeniae fructus[J].Chin J Exp Tradit Med Form,2020,26(16):183-191.
  3. 3.
    ZHANG J H,HU T,ZHOU X W,et al.Research progress on the pharmacological effects and clinical application of Zhizi(Gardeniae Fructus)[J].J Liaoning Univ Tradit Chin Med,2024,26(5):93-98.
  4. 4.
    CHEN R,HE Z X,YAN Y,et al.Research progress on pharmacological and toxic effects of Gardeniae Fructus and its main components[J].Chin Tradit Herb Drugs,2023,54(18):6092-6105.
  5. 5.
    Chinese Pharmacopoeia Commission.Pharmacopoeia of the People's Republic of China:Volume 1[M].Beijing:Chinese Medical Science Press,2020:259-260.
  6. 6.
    ZHENG H R,CHU Y,LI W,et al.Research progress on pharmacokinetics of natural iridoids[J].Drug Eval Res,2018,41(6):1147-1153.
  7. 7.
    XU Y P,CHEN L Y,LIU W L,et al.Advances in inflammaging in liver disease[J].J Zhejiang Univ Med Sci,2025,54(1): 90-98.
  8. 8.
    CHEN G,FAN L Q,YANG T,et al.Prognostic nutritional index(PNI) and risk of non-alcoholic fatty liver disease and advanced liver fibrosis in US adults:Evidence from NHANES 2017-2020[J].Heliyon,2024,10(4):e25660.
  9. 9.
    ZHU L,XUE C Y.Research progress of Keap1-Nrf2 signaling pathway in the prevention and treatment of acute UV damage in cornea[J].Mil Med J Southeast China,2021,23(6):637-641.
  10. 10.
    LIU D,LIU Y,HAO Z F.Research progress of miRNAs in improving lipid metabolism disorders by regulating AMPK signaling pathway[J].Hebei Med J,2023,45(10):1564-1569.
  11. 11.
    SHEN B Y,FENG H H,CHENG J Q,et al.Geniposide alleviates non-alcohol fatty liver disease via regulating Nrf2/AMPK/mTOR signalling pathways[J].J Cell Mol Med,2020,24(9):5097-5108.
  12. 12.
    YANG L,BI L P,JIN L L,et al.Geniposide ameliorates liver fibrosis through reducing oxidative stress and inflammatory respose,inhibiting apoptosis and modulating overall metabolism[J].Front Pharmacol,2021,12:772635.
  13. 13.
    WEN M,LIU Y B,CHEN R Y,et al.Geniposide suppresses liver injury in a mouse model of DDC-induced sclerosing cholangitis[J].Phytother Res,2021,35(7):3799-3811.
  14. 14.
    HUANG W J,XIE X L,SHENG Y M.Pharmacological effects and preparation development progress of verbascoside[J].Chin Tradit Herb Drugs,2024,55(23):8256-8268.
  15. 15.
    CHEN X Y,JIANG W W,LIU Y L,et al.Anti-inflammatory action of geniposide promotes wound healing in diabetic rats[J].Pharm Biol,2022,60(1):294-299.
  16. 16.
    DENG R,LI F,WU H,et al.Anti-inflammatory mechanism of geniposide:Inhibiting the hyperpermeability of fibroblast-like synoviocytes via the RhoA/p38 MAPK/NF-κB/F-actin signal pathway[J].Front Pharmacol,2018,9:105.
  17. 17.
    MO F F,ZHOU J J,JIN L L,et al.Gardenoside anti-inflammatory activity in a rat model of ulcerative colitis by regulation of AMPK/ML-CK signaling[J].Zhejiang J Integr Tradit Chin West Med,2021,31(5):418-424.
  18. 18.
    XU B,LI Y L,XU M,et al.Geniposide ameliorates TNBS-induced experimental colitis in rats via reducing inflammatory cytokine release and restoring impaired intestinal barrier function[J].Acta Pharmacol Sin,2017,38(5):688-698.
  19. 19.
    ZHUGE X J,JIN X S,JI T T,et al.Geniposide ameliorates dextran sulfate sodium-induced ulcerative colitis via KEAP1-Nrf2 signaling pathway[J].J Ethnopharmacol,2023,314:116626.
  20. 20.
    FANG S L,LIU Y C,ZHANG Q H,et al.Study on the analgesic and anti-inflammatory effects of geniposide[J].Lishizhen Med Mater Med Res,2008,19(6):1374-1376.
  21. 21.
    YANG Y,YANG G,ZENG X Y.Analgesic effect of geniposide and its underlying mechanisms[J].Med J Chin People's Armed Police Forces,2013,24(3):218-220.
  22. 22.
    WANG M Y.Study on analgesic effect and mechanism of geniposide on inflammatory pain[D].Nanjing:Nanjing University Of Chinese Medicine,2022.
  23. 23.
    JIN G J,YE Q,XU Z L.The analgsic effect and possible mechanisms of Geniposide on type Ⅱ collagen-induced arthritis in rats[J].Chin J New Drugs,2018,27(3):356-360.
  24. 24.
    ZHANG D D.Geniposide lelieves neuropathic pain in CCI rats by inhibiting the EGFR/PI3K/Akt pathway and Ca2+ channels[D].Hangzhou:Zhejiang Chinese Medical University,2023.
  25. 25.
    SCHELTENS P,DE STROOPER B,KIVIPELTO M,et al.Alzheimer's disease[J].Lancet,2021,397(10284):1577-1590.
  26. 26.
    YANG Z Z,LEI P.Copy number variations of proteins associated with neurodegenerative diseases and rare neurological disorders[J].Sci China Life Sci,2025,55(2):189-205.
  27. 27.
    YE J X,HUANG Q H.Research progress on regulation of β-amyloid protein in alzheimer′s disease by geniposide[J].Liaoning J Tradit Chin Med,2023,50(11):249-252.
  28. 28.
    YE J X,WU J Y,AI L,et al.Geniposide effectively safeguards HT22 cells against Aβ-induced damage by activating mitophagy via the PINK1/Parkin signaling pathway[J].Biochem Pharmacol,2024,226:116296.
  29. 29.
    LIU D X,ZHANG D,HU W M,et al.Geniposide protection against Aβ1-42 toxicity correlates with mTOR inhibition and enhancement of autophagy[J].J Integr Neurosci,2021,20(1):67-75.
  30. 30.
    XIANG S T,XU S W,XIAO H,et al.Geniposide exerts neuroprotective effect in Aβ25-35-induced Alzheimer's disease rat model via ERK1/2-Nrf2 signaling pathway[J].Acta Med Univ Sci Technol Huazhong,2018,47(1):27-32.
  31. 31.
    CUI L X.Studies on the Mechanisms of geniposide in the anti-depressant effect mediated by gut microbiota[D].Shanghai:Naval Medical University,2022.
  32. 32.
    WANG M H,YANG L,CHEN Z L,et al.Geniposide ameliorates chronic unpredictable mild stress induced depression-like behavior through inhibition of ceramide-PP2A signaling via the PI3K/Akt/GSK3β axis[J].Psychopharmacology,2021,238(10):2789-2800.
  33. 33.
    CHEN G H,CHEN Q,ZHANG L L,et al.Effects of gardeniin on the expression of collapsin response mediator protein 2 and potential molecular mechanism in prefrontal cortex of depression model rats[J].Front Pharm Sci,2021,24(10):1794-1799.
  34. 34.
    TAN H M,ZHOU L,ZOU H C.Geniposide-mediated GLP-1R/Akt signaling pathway improves cerebral ischemia-reperfusion injury and neuronal apoptosis in rats[J].Drug Eval Res,2022,45(9):1822-1829.
  35. 35.
    ZHOU S,LI H M,ZHANG H H,et al.Effect of baicalin-geniposide compatibility on the brain tissue injury in rats with focal cerebral ischemia-reperfusion via LTB4/BLTR pathway[J].Cent South Pharm,2022,20(6):1255-1261.
  36. 36.
    LIU Z,ZHONG J Y,GAO E N,et al.Synergistic protective effects of gardenoside,ligustrazine and puerarin on ischemia-reperfusion-induced cerebral injury[J].Chin Tradit Pat Med,2020,42(7):1754-1759.
  37. 37.
    LI H Y,YANG D H,ZHANG Y M,et al.Geniposide suppresses NLRP3 inflammasome-mediated pyroptosis via the AMPK signaling pathway to mitigate myocardial ischemia/reperfusion injury[J].Chin Med,2022,17(1):73.
  38. 38.
    MA J A,LIU X M,DENG J F,et al.Protective effect of geniposide against myocardial ischemia reperfusion injuries and its relationship with PI3K/Akt signaling pathway in rats[J].J Clin Exp Med,2018,17(20):2152-2155.
  39. 39.
    MA X F,JIAO Y R,ZHANG J J.Effects of geniposide on inflammatory response,oxidative stress,and PI3K/Akt signal pathway in rats with hepatic ischemia-reperfusion injury[J].Drugs Clin,2023,38(1):29-36.
  40. 40.
    HANG W D,BAN J Y,ZHAO Z Y,et al.Geniposide protects against lung ischemia-reperfusion injury by modulating p-Akt and NF-κB expression[J].Chin Community Doctors,2019,35(4):5-6.
  41. 41.
    CHEN F,WANG Y,LI L S.Protective effects of geniposide on renal ischemic reperfusion injury in mice[J].Pharm J Chin People's Liberation Army,2017,33(6):550-553.
  42. 42.
    GUI K H,ZHANG H Y,HUANG L,et al.Effects of geniposide on the edema and neuronal apoptosis in spinal cord ischemia/reperfusion injury[J].J Clin Exp Med,2017,16(12):1157-1160.
  43. 43.
    YU X,WANG Y,TAO S J,et al.Geniposide plays anti-tumor effects by down-regulation of microRNA-224 in HepG2 and Huh7 cell lines[J].Exp Mol Pathol,2020,112:104349.
  44. 44.
    ZHANG C,WANG N,TAN H Y,et al.Direct inhibition of the TLR4/MyD88 pathway by geniposide suppresses HIF-1α-independent VEGF expression and angiogenesis in hepatocellular carcinoma[J].Br J Pharmacol,2020,177(14):3240-3257.
  45. 45.
    SHI Y L,ZHOU P,WANG X K,et al.Regulation of geniposideon on the proliferation,pyroptosis and invasion of breast cancer cells through AMPK/SIRT1/NF-κB pathway[J].J Guangxi Med Univ,2022,39(11):1700-1705.
  46. 46.
    ZHU L,LIU Z W,CUI Q W,et al.Epigenetic modification of CD4+ T cells into Tregs by 5-azacytidine as cellular therapeutic for atherosclerosis treatment[J].Cell Death Dis,2024,15(9):689.
  47. 47.
    WU J,WU J,XIAO K,et al.Effect of geniposide regulating PI3K/Akt/mTOR signaling pathway on Th17/Treg function during atherogenesis[J].Chin J Integr Med Cardio-Cerebrovasc Dis,2024,22(5):817-822.
  48. 48.
    YANG X D.Based on P2RY12 receptor mediated PI3K/Akt/mTOR autophagy signal pathway to explore the mechanism of GP intervention on AS[D].Guangzhou:Guangzhou University of Chinese Medicine,2023.
  49. 49.
    HE P K,WANG H,CHENG S B,et al.Geniposide ameliorates atherosclerosis by regulating macrophage polarization via perivascular adipocyte-derived CXCL14[J].J Ethnopharmacol,2023,314:116532.
  50. 50.
    XIAO Y S,ZHANG S S,YE Y J,et al.Geniposide suppressed OX-LDL-induced osteoblast apoptosis by regulating the NRF2/NF-κB signaling pathway[J].J Orthop Surg Res,2023,18(1):641.
  51. 51.
    HUANG J S,YE Y J,XIAO Y S,et al.Geniposide ameliorates glucocorticoid-induced osteoblast apoptosis by activating autophagy[J].Biomed Pharmacother,2022,155:113829.
  52. 52.
    XIAO Y S,REN Q,ZHENG Y Z,et al.Geniposide ameliorated dexamethasone-induced endoplasmic reticulum stress and mitochondrial apoptosis in osteoblasts[J].J Ethnopharmacol,2022,291:115154.
  53. 53.
    ZHENG Y Z,XIAO Y S,ZHANG D,et al.Geniposide ameliorated dexamethasone-induced cholesterol accumulation in osteoblasts by mediating the GLP-1R/ABCA1 axis[J].Cells,2021,10(12):3424.
  54. 54.
    XIE B C,WU J H,LI Y M,et al.Geniposide alleviates glucocorticoid-induced inhibition of osteogenic differentiation in MC3T3-E1 cells by ERK pathway[J].Front Pharmacol,2019,10:411.
  55. 55.
    ZHANG H Y.Geniposide/bmcalin cardiovascular function and applied to the stent coatings[D].Chengdu:Southwest Jiaotong University,2014.
  56. 56.
    WANG Y F,XU Q H,DUAN M L.Regulatory effect of geniposide on influenza virus-induced lung injury in mice based on the TLR3/TRIF pathway[J].Chin J Virol,2020,36(1):35-43.
  57. 57.
    ZHANG Y S,QI X,LU X Q,et al.Inhibitory effect of geniposide against influenza A/H1N1 virus[J].J China Pharm Univ,2016,47(2):204-209.
  58. 58.
    CHEN J J,LIU Y,YIN N N,et al.Geniposide alleviates imiquimod-induced psoriasis-like skin lesions in mice via inhibition of angiogenesis[J].Int Immunopharmacol,2024,132:111923.
  59. 59.
    YIN J B,WANG Y X,FAN S S,et al.Geniposide ameliorates bleomycin-induced pulmonary fibrosis in mice by inhibiting TGF-β/Smad and p38 MAPK signaling pathways[J].PLoS One,2024,19(9):e309833.
  60. 60.
    CHANG R R.Isoflavones influence on pharmacokinetic profiles of main iridoids from cardeniae fructus in rat[D].Hefei:Anhui University of Traditional Chinese Medicine,2019.
  61. 61.
    SUN W Q,CHEN X K,JIANG Y,et al.Research progress on the pharmacokinetics of geniposide[J].Biol Chem Eng,2022,8(2):141-143.
  62. 62.
    YANG M,CHEN X Y,ZHANG H Y,et al.Pharmacokinetics of geniposide through 4 routes of administration[J].Chin J New Drugs,2010,19(9):746-749.
  63. 63.
    SHAN M Q,YU S,YAN H,et al.A review on the phytochemistry,pharmacology,pharmacokinetics and toxicology of geniposide,a natural product[J].Molecules,2017,22(10):1689.
  64. 64.
    ZHENG W H,WANG Y J,LIANG J J,et al.Comparison of pharmacokinetics between reduning injection and geniposide monomer in rats in vivo[J].Chin J Exp Tradit Med Form,2014,20(3):95-99.
  65. 65.
    GAO A,ZHANG W S,FENG C Q.Absorption,distribution,metabolism and excretion and the hepatotoxicity of geniposide:A research progress[J].Chin J Pharmacol Toxicol,2022,36(7):552-558.
  66. 66.
    WANG F G,CAO J,HAO J F,et al.Pharmacokinetics,bioavailability and tissue distribution of geniposide following intravenous and peroral administration to rats[J].Biopharm Drug Dispos,2014,35(2):97-103.
  67. 67.
    HU F D,AN J,LI W,et al.UPLC-MS/MS determination and gender-related pharmacokinetic study of five active ingredients in rat plasma after oral administration of Eucommia cortex extract[J].J Ethnopharmacol,2015,169:145-155.
  68. 68.
    XU Y L,PU Y C,ZHU L D,et al.A pharmacokinetic study of berberin and gardenoside in rats after oral administration of Zhizi Baipi tablet[J].Prog Mod Biomed,2019,19(5):834-837.
  69. 69.
    JIANG H Y,YAN S M,WU Q H,et al.Research progress of novel preparations of polysaccharides[J].China J Chin Mater Med,2020,45(19):4582-4588.
  70. 70.
    JAFARI A,DANESHAMOUZ S,GHASEMIYEH P,et al.Ethosomes as dermal/transdermal drug delivery systems:Applications,preparation and characterization[J].J Liposome Res,2023,33(1):34-52.
  71. 71.
    ALMEIDA B,NAG O K,ROGERS K E,et al.Recent progress in bioconjugation strategies for liposome-mediated drug delivery[J].Molecules,2020,25(23):5672.
  72. 72.
    FENG H X,LI P S,LIU Y X,et al.Advances in research and application of liposomes[J].Prog Pharm Sci,2024,48(10):725-734.
  73. 73.
    CAO J,HOU X Q,WANG F G.Optimization on the preparation of gardenoside liposomes by central composite design-response surface method[J].Her Med,2021,40(6):797-801.
  74. 74.
    LI Z X,ZHU H M,LIU H,et al.Synergistic dual cell therapy for atherosclerosis regression:ROS-responsive bio-liposomes co-loaded with geniposide and emodin[J].J Nanobiotechnology,2024,22(1):129.
  75. 75.
    WAN J Y,LONG Y,LIU S Y,et al.Geniposide-loaded liposomes for brain targeting:Development,evaluation,and in vivo studies[J].AAPS Pharm Sci Tech,2021,22(7):222.
  76. 76.
    PAIVA-SANTOS A C,SILVA A L,GUERRA C,et al.Ethosomes as nanocarriers for the development of skin delivery formulations[J].Pharm Res,2021,38(6):947-970.
  77. 77.
    SONG Y L,HAN T F,LI S S,et al.Preparation of nasal ethosome spray of geniposide and its nasal mucosa permeability in vitro[J].Chin Tradit Herb Drugs,2013,44(9):1105-1110.
  78. 78.
    DONG W M,JIANG C Z,YE J C,et al.Advances in penetration promoting approach of transdermal drug delivery systems[J].Chin J New Drugs,2020,29(18):2089-2097.
  79. 79.
    LIANG Y,ZHANG Z R.Research development in transfersome-based drug delivery system[J].J Sichuan Univ:Med Sci Ed,2021,52(4):543-547.
  80. 80.
    LI Z Q,CHEN X,CAO D Y,et al.Research progress on deformable nanocapsular carrier-transferosomes in transdermal preparations[J].Her Med,2024,43(8):1302-1308.
  81. 81.
    YAN H,GAO S Q,LUO H T,et al.Preparation of hyaluronic acid-modified geniposide transfersomes gels and its pharmacodynamic evaluation for adjuvant arthritis[J].Chin Tradit Herb Drugs,2023,54(18):5867-5879.
  82. 82.
    MA P P,LI Q,OU G,et al.The combined therapeutic effects of 5-aminolevulinic acid cubic liquid crystal and light needles for basal cell cancer[J].Acta Pharm Sin,2021,56(3):865-871.
  83. 83.
    SI Q.Preparation of matrine lipid-based cubic liquid crystalline nanoparticle gel and its pharmacological evaluation study[D].Beijing:China Academy of Chinese Medical Sciences,2022.
  84. 84.
    OUYANG W,HUANG X Y,WANG X Y,et al.Preparation,characterization,and in vitro evaluation of geniposide cubic liquid crystal gel[J].J Hunan Univ Chin Med,2024,44(1):38-46.
  85. 85.
    ZENG T Y,HUANG X Y,GAO S Q,et al.Comparison of transdermal capability in vitro and rheology between geniposide cubic liquid crystals gel and its ointment[J].Asia-Pac Tradit Med,2021,17(4):30-36.
  86. 86.
    MCCLEMENTS D J.Advances in nanoparticle and microparticle delivery systems for increasing the dispersibility,stability,and bioactivity of phytochemicals[J].Biotechnol Adv,2020,38:107287.
  87. 87.
    WANG Y T,JIANG S L,WANG H L,et al.A mucoadhesive,thermoreversible in situ nasal gel of geniposide for neurodegenerative diseases[J].PLoS One,2017,12(12):e0189478.
  88. 88.
    LI H Y,TIAN M L,WANG C L,et al.A novel Thermo-responsive hydrogel system ( THS ) loaded with the active ingredient of Gardenia jasminoides J.Ellis exhibits anti-depressant effects in vivo via intranasal administration[J].J Drug Deliv Sci Technol,2023,81:104223.
  89. 89.
    XU W T,BAE E J,LEE M K.Enhanced anticancer activity and intracellular uptake of paclitaxel-containing solid lipid nanoparticles in multidrug-resistant breast cancer cells[J].Int J Nanomed,2018,13:7549-7563.
  90. 90.
    SIVADASAN D,RAMAKRISHNAN K,MAHENDRAN J,et al.Solid lipid nanoparticles:Applications and prospects in cancer treatment[J].Int J Mol Sci,2023,24(7):6199.
  91. 91.
    WANG F G,CAO J,HAO J F,et al.Pharmacokinetics,tissue distribution and relative bioavailability of geniposide-solid lipid nanoparticles following oral administration[J].J Microencapsul,2014,31(4):382-389.
  92. 92.
    TANG L,WU L,SUN B X,et al.Preparation and evaluation of geniposide phospholipids complex[J].J Zhejiang Univ Technol,46(1):110-113.
  93. 93.
    WU T,WANG J Y,YE Q Z,et al.Preparation and evaluation of geniposide phospholipid complex[J].Chin J Pharm:Online Edition,2019,17(1):1-11.
  94. 94.
    TANG L,YU X L,ZHU Z F,et al.Effect of phospholipid complex on the degradation of geniposide by rat intestinal flora in vitro[J].Chin Pharm J,2018,53(24):2090-2095.
  95. 95.
    LI H S,XI Y F,XIN X,et al.Study on mechanism of gardenoside in treatment of nonalcoholic steatohepatitis based on bile acid signaling pathway[J].Chin Arch Tradit Chin Med,2023,41(9):30-36.
  96. 96.
    DU Z,QIU J N,GUO Z,et al.Efficacy/hepatoxicity mechanism of geniposide with different doses and courses in the regulation of chronic cholestasis[J].China J Tradit Chin Med Pharm,2022,37(7):4048-4053.
  97. 97.
    HAN J Q,LIU Z P.Research progress of transdermal drug delivery system[J].Prog Biomed Eng,2022,43(1):24-28.
  98. 98.
    XIN X Y,XIONG J,MAO D H,et al.Research progress on intranasal mucosal drug delivery for ischemic stroke treatment[J].J Pract Tradit Chin Med,2025,41(1):209-214.

Leia o texto completo

The above content is generated by Large Model Translation. The translated content is for reference only. We do not assume any commercial or legal responsibilty for any consequences arising from the use of our website