4-Hydroxybenzyl alcohol

4-Hydroxybenzyl alcohol derivatives and their sedative-hypnotic activities

4-Hydroxybenzyl alcohol (HBA), one of the characteristic active components of Gastrodia elata, exhibits obvious effects on the human central nervous system. In order to acquire compounds with superior bioactivity, 10 derivatives of HBA were synthesized from HBA and carboxylic acids. The sedative effects of the 10 HBA derivatives were evaluated using a spontaneous locomotor activity test (SLT) in mice, and their hypnotic effects were determined to be synergistic with pentobarbital-induced sleep. The results showed that 4-hydroxybenzyl alcohol 3-furancarboxylic acid diester (2FHBA, 10 mg kg-1) exhibited the strongest sedative-hypnotic activity among HBA and its derivatives, and 2FHBA could reverse the insomnia caused by p-chlorophenylalanine (pCPA), flumazenil (FLU) and thiosemicarbazide (TSC). Meanwhile, 2FHBA and 5-hydroxytryptophan (5-HTP) showed a synergistic effect. The results suggested that 2FHBA might be a potential agent against insomnia, which might be mediated by the serotonergic and GABAergic systems.

[Metabolic engineering study on biosynthesis of 4-hydroxybenzyl alcohol from L-tyrosine in Escherichia coli]

As an important active ingredient in the rare Chinese herb Gastrodiae Rhizoma and also the main precursor for gastrodin biosynthesis, 4-hydroxybenzyl alcohol has multiple pharmacological activities such as anti-inflammation, anti-tumor, and anti-cerebral ischemia. The pharmaceutical products with 4-hydroxybenzyl alcohol as the main component have been increasingly favored. At present, 4-hydroxybenzyl alcohol is mainly obtained by natural extraction and chemical synthesis, both of which, however, exhibit some shortcomings that limit the long-term application of 4-hydroxybenzyl alcohol. The wild and cultivated Gastrodia elata resources are limited. The chemical synthesis requires many steps, long time, and harsh reaction conditions. Besides, the resulting by-products are massive and three reaction wastes are difficult to treat. Therefore, how to artificially prepare 4-hydroxybenzyl alcohol with high yield and purity has become an urgent problem facing the medical researchers. Guided by the theory of microbial metabolic engineering, this study employed the genetic engineering technologies to introduce three genes ThiH, pchF and pchC into Escherichia coli for synthesizing 4-hydroxybenzyl alcohol with L-tyrosine. And the fermentation conditions of engineering strain for producing 4-hydroxybenzyl alcohol in shake flask were also discussed. The experimental results showed that under the conditions of 0.5 mmol﹞L~(-1) IPTG, 15 ⊥ induction temperature, and 40 ⊥ transformation temperature, M9 Y medium containing 200 mg﹞L~(-1) L-tyrosine could be transformed into(69㊣5)mg﹞L~(-1) 4-hydroxybenzyl alcohol, which has laid a foundation for producing 4-hydroxybenzyl alcohol economically and efficiently by further expanding the fermentation scale in the future.

Plants as source of new therapies for endometriosis: a review of preclinical and clinical studies

Background: Given the disadvantages and limitations of current endometriosis therapy, there is a progressive increase in studies focusing on plant-derived agents as a natural treatment option with the intention of achieving high efficiency, avoiding adverse effects and preserving the chance for successful pregnancy. The heterogeneity of these studies in terms of evaluated agents, applied approaches and outcomes illustrates the need for an up-to-date summary and critical view on this rapidly growing field in endometriosis research.
Objective and rationale: This review provides a comprehensive overview of plant-derived agents and natural treatment strategies that are under preclinical or clinical investigation and critically evaluates their potential for future endometriosis therapy.
Search methods: An English language PubMed literature search was performed using variations of the terms 'endometriosis', 'natural therapy', 'herb/herbal', 'plant', 'flavonoid', 'polyphenol', 'phytochemical', 'bioactive', 'Kampo' and 'Chinese medicine'. It included both animal and human studies. Moreover, the Clinicaltrials.gov database was searched with the term 'endometriosis' for clinical trials on plant-derived agents. No restriction was set for the publication date.
Outcomes: Natural therapies can be assigned to three categories: (i) herbal extracts, (ii) specific plant-derived bioactive compounds and (iii) Chinese herbal medicine (CHM). Agents of the first category have been shown to exert anti-proliferative, anti-inflammatory, anti-angiogenic and anti-oxidant effects on endometrial cells and endometriotic lesions. However, the existing evidence supporting their use in endometriosis therapy is quite limited. The most studied specific plant-derived bioactive compounds are resveratrol, epigallocatechin-3-gallate, curcumin, puerarin, ginsenosides, xanthohumol, 4-hydroxybenzyl alcohol, quercetin, apigenin, carnosic acid, rosmarinic acid, wogonin, baicalein, parthenolide, andrographolide and cannabinoids, with solid evidence about their inhibitory activity in experimental endometriosis models. Their mechanisms of action include pleiotropic effects on known signalling effectors: oestrogen receptor-汐, cyclooxygenase-2, interleukin-1 and -6, tumour necrosis factor-汐, intercellular adhesion molecule-1, vascular endothelial growth factor, nuclear factor-kappa B, matrix metalloproteinases as well as reactive oxygen species (ROS) and apoptosis-related proteins. Numerous studies suggest that treatment with CHM is a good choice for endometriosis management. Even under clinical conditions, this approach has already been shown to decrease the size of endometriotic lesions, alleviate chronic pelvic pain and reduce postoperative recurrence rates.
Wider implications: The necessity to manage endometriosis as a chronic disease highlights the importance of identifying novel and affordable long-term safety therapeutics. For this purpose, natural plant-derived agents represent promising candidates. Many of these agents exhibit a pleiotropic action profile, which simultaneously inhibits fundamental processes in the pathogenesis of endometriosis, such as proliferation, inflammation, ROS formation and angiogenesis. Hence, their inclusion into multimodal treatment concepts may essentially contribute to increase the therapeutic efficiency and reduce the side effects of future endometriosis therapy.

4-Hydroxybenzyl alcohol confers neuroprotection through up-regulation of antioxidant protein expression

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. 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. 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.

4-hydroxybenzyl alcohol ameliorates cerebral injury in rats by antioxidant action

4-hydroxybenzyl alcohol (4-HBA), one of the phenolic constituents found in many herbal medicinal plants, exhibits beneficial effects in neurological disorders. In the present study, we evaluated 4-HBA's role in transient cerebral ischemia and its potential mechanism. Pre-treatment with 4-HBA (50,100 mg/kg) significantly reduced the cerebral infarct size and improved the neurological symptoms. Morphological examinations showed 4-HBA reduced the number of degenerated neurons. Oxidative stress was evaluated superoxide dismutase (SOD) activity and malondialdehyde (MDA) level. Anti-oxidative mechanisms were studied by Immunofluorescence staining and western immunoblot analysis. 4-HBA increased the expression of NAD(P)H: quinone oxidoreductase1 (NQO1) and ultimately inhibited oxidative stress. In addition, we evaluated the time course expression of NQO1, which was upregulated in the ischemic brain beginning at 1 h. Taken together, these results suggested that 4-HBA ameliorated cerebral injury in rats, This neuroprotective effect is likely related to its antioxidant activities.