4-Hydroxybenzyl alcohol

Life Sci. 2013 Jul 19;93(1):44-50.

4-hydroxybenzyl alcohol: a novel inhibitor of tumor angiogenesis and growth.[Pubmed: 23743167]

The herbal compound 4-Hydroxybenzyl alcohol (HBA) is a pleiotropic agent, which has been shown to effectively inhibit the development of new blood vessels by targeting multiple mechanisms of the angiogenic process. Because angiogenesis is a major prerequisite for tumor growth, the aim of this study was to analyze for the first time, whether 4-Hydroxybenzyl alcohol may be used for anti-cancer therapy.
METHODS AND RESULTS:
CT26.WT colon carcinoma cells were exposed to different 4-Hydroxybenzyl alcohol doses to study their viability, migration, invasiveness and protein expression compared to vehicle-treated controls. Moreover, CT26.WT cell spheroids were transplanted into the dorsal skinfold chamber of 4-Hydroxybenzyl alcohol-treated and vehicle-treated BALB/c mice for the analysis of tumor vascularization and growth by means of repetitive intravital fluorescence microscopy, histology and immunohistochemistry. As shown by water-soluble tetrazolium (WST)-1 and lactate dehydrogenase (LDH) assays, 4-Hydroxybenzyl alcohol treatment dose-dependently reduced the viability and integrity of the tumor cells. Moreover, phalloidin staining of 4-Hydroxybenzyl alcohol-treated cells revealed a disorganized cytoskeleton, which was associated with a decreased cellular migratory and invasive activity. Finally, 4-Hydroxybenzyl alcohol treatment inhibited the vascularization and growth of newly developing CT26.WT tumors in the mouse dorsal skinfold chamber model without affecting the normal behavior of the animals.
CONCLUSIONS:
These novel findings indicate that 4-Hydroxybenzyl alcohol represents a promising candidate for the establishment of anti-angiogenic treatment strategies in cancer therapy.

J Ethnopharmacol. 2012 Jan 31;139(2):549-57.

Modulation of LPS-stimulated neuroinflammation in BV-2 microglia by Gastrodia elata: 4-hydroxybenzyl alcohol is the bioactive candidate.[Pubmed: 22155394]

4-Hydroxybenzyl alcohol (HBA) is a phenolic plant compound, which has been shown to influence many cellular mechanisms. In the present study, we analysed in vitro and in vivo the anti-angiogenic actions of this pleiotropic agent.
METHODS AND RESULTS:
Migration and protein expression of 4-Hydroxybenzyl alcohol- and vehicle-treated endothelial-like eEND2 cells was assessed by cell migration assay and Western blot analyses. 4-Hydroxybenzyl alcohol action on vascular sprouting was analysed in an aortic ring assay. In vivo anti-angiogenic actions of 4-Hydroxybenzyl alcohol were studied in the dorsal skinfold chamber model of endometriosis in mice. Western blot analyses demonstrated that 4-Hydroxybenzyl alcohol inhibited proliferation of eEND2 cells, as indicated by down-regulation of proliferating cell nuclear antigen expression, and reduced expression of vascular endothelial growth factor and matrix metalloproteinase 9. 4-Hydroxybenzyl alcohol suppressed the migration of eEND2 cells, accompanied by inhibition of actin filament reorganization, revealed by fluorescence staining of the cytoskeleton. In addition, 4-Hydroxybenzyl alcohol reduced vascular sprouting in the aortic ring assay. Finally, we found, in the dorsal skinfold chamber model in vivo using intravital fluorescence microscopy, that 4-Hydroxybenzyl alcohol inhibited the vascularization of developing endometriotic lesions, as indicated by a decreased functional capillary density of lesions in 4-Hydroxybenzyl alcohol-treated mice and a reduced lesion size, compared with control animals.
CONCLUSIONS:
4-Hydroxybenzyl alcohol targets several angiogenic mechanisms and therefore represents a promising anti-angiogenic agent for the treatment of angiogenic diseases, such as endometriosis.

J Pharm Pharmacol. 2007 Sep;59(9):1235-40.

Anti-angiogenic, anti-inflammatory and anti-nociceptive activity of 4-hydroxybenzyl alcohol.[Pubmed: 17883894 ]

METHODS AND RESULTS:
4-Hydroxybenzyl alcohol (HBA), one of the well-known phenolic compounds in diverse plants, displayed a significant inhibition in the chick chorioallantoic membrane (CAM) angiogenesis assay. HBA was shown to contain an anti-inflammatory activity in carrageenan-induced air pouch model in rats and acetic acid-induced permeability model in mice. Anti-nociceptive activity of HBA was also assessed using the acetic acid-induced writhing test in mice. HBA was able to suppress production of nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. In the macrophages, the level of reactive oxygen species (ROS) was diminished by HBA.
CONCLUSIONS:
Taken together, HBA possesses anti-angiogenic, anti-inflammatory and anti-nociceptive activity possibly via its down-regulating activity on NO production, which may be partly responsible for the pharmacological efficacy of several folkloric medicines.

Neurochem Res. 2013 Jul;38(7):1501-16.

4-Hydroxybenzyl alcohol confers neuroprotection through up-regulation of antioxidant protein expression.[Pubmed: 23624876]

An herb-derived phenolic compound, 4-Hydroxybenzyl alcohol (4-HBA), exhibits beneficial effects in cerebral ischemic injury. However, the molecular mechanisms underlying this observation remain unclear.
METHODS AND RESULTS:
Here we used an in vitro ischemic model of oxygen-glucose deprivation followed by reperfusion (OGD/R) and an in vivo ischemic model of middle cerebral artery occlusion to investigate the relevant neuroprotective mechanisms. We demonstrated that 4-HBA reduced the neuronal injury, LDH release, and up-regulation of 8-hydroxydeoxyguanosine (8-OHdG) induced by OGD/R. Furthermore, 4-HBA reduced the cerebral infarct size and improved the behavioral parameters after cerebral ischemia. These neuroprotective effects may be conferred by the 4-HBA mediated upregulation of the transcription factor nuclear factor E2-related factor 2 (Nrf2), peroxiredoxin 6 (Prdx6) and protein disulfide isomerase (PDI) by the use of 4-HBA. Interestingly, LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, blocked the increase in phosphorylation of Akt and abolished the neuroprotection associated with 4-HBA.
CONCLUSIONS:
Our results suggested that 4-HBA protects neurons against cerebral ischemic injury, and this neuroprotection may occur through upregulation of Nrf2, Prdx6, and PDI expression via the PI3K/Akt pathway.

Brain Res. 2010 Jan 13;1308:167-75.

Neuroprotective effect of 4-hydroxybenzyl alcohol against transient focal cerebral ischemia via anti-apoptosis in rats.[Pubmed: 19857470]

4-Hydroxybenzyl alcohol (4-HBA), one of the major active phenolic constituents of Gastrodia elata Blume, a very important traditional Chinese medicinal herb, has been shown to be an effective agent against the central and peripheral nervous disorders.
METHODS AND RESULTS:
In this study, we attempted to explore the possible mechanisms underlying the neuroprotection against transient focal cerebral ischemia by 4-HBA.4-HBA (25, 50 mg/kg) was given 30 min before focal ischemia in rats caused by middle cerebral artery occlusion (1 h of occlusion, 24 h of reperfusion). Under the treatment of 50 mg/kg 4-HBA, total (100.76+/-2.90 mm(3)), cortical (64.91+/-1.46 mm(3)), and sub-cortical (38.77+/-2.78 mm(3)) infarct volumes were significantly decreased in comparison to ischemia-reperfusion values. Neurological evaluation and Nissl-staining of the 4-HBA group were improved significantly compared to the untreated ischemia group. TUNEL-positive cells were reduced significantly in 4-HBA treated group. Results of immunofluorescence staining analysis and Western immunoblot indicated that 4-HBA increased the expression of Bcl-2 and inhibited the activation of caspase-3 ultimately inhibiting apoptosis.
CONCLUSIONS:
These results suggested that 4-HBA ameliorated ischemic injury induced by transient focal cerebral ischemia in rats, and this neuroprotective effect may be partly related to attenuate apoptosis pathway.