Disease relevance of Honokiol

• Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and -independent apoptosis [1].
• The natural product honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells [2].
• In vivo, honokiol was highly effective against angiosarcoma in nude mice [3].
• In this study, we first investigated the in vivo effects of honokiol on rat anti-Thy1 nephritis [4].
• Honokiol demonstrated weak activity against HIV-1 in human lymphocytes [5].

Psychiatry related information on Honokiol

• Use of the elevated plus-maze experiment and activity and traction tests in mice have revealed that seven daily treatments with 0.2 mg kg(-1) and higher doses of honokiol, a neolignane derivative extracted from Magnolia bark, had an anxiolytic effect without change in motor activity or muscle tone [6].

High impact information on Honokiol

• Honokiol-induced apoptosis was characterized by the activation of caspase-3, -8, and -9 and cleavage of poly(adenosine diphosphate-ribose) polymerase (PARP) [2].
• Honokiol induced caspase-dependent cell death in all of the B-CLL cells examined and was more toxic toward B-CLL cells than to normal mononuclear cells, suggesting greater susceptibility of the malignant cells [2].
• Exposure of B-CLL cells to honokiol resulted in up-regulation of Bcl2-associated protein (Bax) and down-regulation of the expression of the key survival protein myeloid-cell leukemia sequence 1 (Mcl-1), which is associated with response to treatment in B-CLL patients [2].
• In addition, B-CLL cells pretreated with interleukin-4 (IL-4), a cytokine known to support B-CLL survival, underwent apoptosis when subsequently incubated with honokiol, indicating that honokiol could also overcome the prosurvival effects of IL-4 [2].
• In addition, honokiol demonstrated preferential inhibition of primary human endothelial cells compared with fibroblasts and this inhibition was antagonized by antibodies against TNF alpha-related apoptosis-inducing ligand [3].

Chemical compound and disease context of Honokiol

• These results demonstrated that the neuroprotective effects of honokiol and magnolol may be related to their anti-oxidative actions and antagonism of excitotoxicity induced by excitatory amino acids, suggesting that both compounds may be potential therapeutic agents for neurodegenerative diseases [7].
• We recently demonstrated that honokiol inhibited arterial thrombosis through stimulation of prostacyclin (PGI(2)) generation and endothelial cell protection [8].
• The aim of the present study was to investigate the neuroprotective effects of honokiol and magnolol, two major bioactive constituents of the bark of Magnolia officinalis, against neuron toxicity induced by glucose deprivation, excitatory amino acids and hydrogen peroxide (H(2)O(2)) in cultured rat cerebellar granule cells [7].
• CONCLUSIONS.: The combination of honokiol and low-dose docetaxel may be used to improve patient outcome in androgen-independent prostate cancer with bone metastasis [9].
• Antiarrhythmic effect of magnolol and honokiol during acute phase of coronary occlusion in anesthetized rats: influence of L-NAME and aspirin [10].

Biological context of Honokiol

• The increased intraglomerular proliferating cell nuclear antigen and Akt phosphorylation in nephritic rats could be abolished by the treatment of honokiol [4].
• Magnolol and honokiol isolated from Magnolia officinalis protect rat heart mitochondria against lipid peroxidation [11].
• In summary, our results demonstrate that honokiol suppresses NF-kappaB activation and NF-kappaB-regulated gene expression through the inhibition of IKKs, which provides a possible mechanism for its anti-tumor actions [12].
• Here, we found that honokiol-induced apoptotic cell death was accompanied by upregulation of Bad and downregulation of Bcl-XL, while honokiol had no effect on the levels of Bcl-2, Bcl-XS, Bag-1, Bax and Bak proteins [13].
• In this study, we investigated whether honokiol affects the transcription factor nuclear factor-kappa B (NF-kappaB) which controls a large number of genes involved in angiogenesis, metastasis and cell survival [12].

Anatomical context of Honokiol

• We observed that the tumor necrosis factor-alpha (TNF-alpha)-induced NF-kappaB activation was blocked by honokiol in four different cancer cell lines as evidenced by EMSA [12].
• Moreover, honokiol treatment caused the release of mitochondrial cytochrome c to cytosol and sequential activation of caspases [13].
• In addition, at lower concentration (0.376-3.76 muM), honokiol significantly decreased the percentage of apoptotic endothelial cells induced by oxidized low-density lipoprotein (ox-LDL) and significantly lowered the activity of caspase-3 stimulated by ox-LDL [8].
• The anti-inflammatory effect of honokiol on neutrophils: mechanisms in the inhibition of reactive oxygen species production [14].
• Primary rat hepatocytes were pretreated with honokiol at concentrations of 40, 20 and 10 microM 5 min before glycochenodeoxycholic acid treatment [15].

Associations of Honokiol with other chemical compounds

• Honokiol and magnolol were well separated within 7 min in a 40 cm long capillary at a separation voltage of 15 kV using a 50 mM borate buffer (pH 9.2) [16].
• Carbon nanotube/poly(methyl methacrylate) composite electrode for capillary electrophoretic measurement of honokiol and magnolol in Cortex Magnoliae Officinalis [16].
• The antioxidant effects of magnolol and honokiol purified from Magnolia officinalis were 1000 times higher than that of alpha-tocopherol [11].
• Magnolol and honokiol enhance HL-60 human leukemia cell differentiation induced by 1,25-dihydroxyvitamin D3 and retinoic acid [17].
• Honokiol up-regulates prostacyclin synthease protein expression and inhibits endothelial cell apoptosis [8].

Gene context of Honokiol

• Using a nuclear factor-kappaB (NF-kappaB) luciferase reporter assay system and Western analysis, we identified that magnolol and honokiol exert their anti-inflammatory effects by inhibiting the NF-kappaB element, which exists in Cox-2, IL-8, and TNF-alpha promoters [(15 microM magnolol: 44.8% inhibition), (15 microM honokiol: 42.3% inhibition)] [18].
• The phosphorylation of ERK1/2 enhanced by honokiol was inhibited by PD98059 as well as by KN93, a Ca2+/calmodulin-dependent kinase II (CaMK II) inhibitor [19].
• Cyclooxygenase-2 (Cox-2) activity was also suppressed by them [(15 microM magnolol: 45.8% inhibition), (15 microM honokiol: 66.3% inhibition)] [18].
• Thus, overall, our results indicate that NF-kappaB and NF-kappaB-regulated gene expression inhibited by honokiol enhances apoptosis and suppresses osteoclastogenesis and invasion [20].
• Magnolol and honokiol inhibited the activity of MMP-9, which may have been responsible, in part, for the inhibition of tumor cell invasiveness [21].
• Exposure of human prostate cancer cells (PC-3, LNCaP, and C4-2) to honokiol resulted in apoptotic DNA fragmentation in a concentration- and time-dependent manner irrespective of their androgen responsiveness or p53 status [22].
• Although HNSCC xenograft models did not show significant inhibition of in vivo tumor growth with honokiol treatment alone, the combination of honokiol plus cetuximab, a Food and Drug Administration-approved EGFR inhibitor for this malignancy, significantly enhanced growth inhibition [23].

Analytical, diagnostic and therapeutic context of Honokiol

• The performance of this unique system has been demonstrated by separating and detecting honokiol and magnolol in traditional Chinese medicine, Cortex Magnoliae Officinalis [16].
• In rats subjected to 4 hours coronary ligation, 10(-7) g/kg, 10(-8) g/kg, and 10(-9) g/kg honokiol significantly reduced the infarct zone [24].
• We concluded that honokiol may protect the myocardium against ischemic injury and suppress ventricular arrhythmia during ischemia and reperfusion [24].
• The results showed that there was no significant hemodynamic change after intravenous infusion of honokiol at the dosages of 10(-8), 10(-7) and 10(-6) g/kg in both groups [25].
• Honokiol also inhibited immunoglobulin E-mediated production of these LTs in RBL-2H3 cells, which was measured by a specific radioimmunoassay (RIA) [26].

References