Apitherapy in Post-Ischemic Brain Neurodegeneration of Alzheimer's Disease Proteinopathy: Focus on Honey and Its Flavonoids and Phenolic Acids.

Neurodegeneration of the brain after ischemia is a major cause of severe, long-term disability, dementia, and mortality, which is a global problem. These phenomena are attributed to excitotoxicity, changes in the blood-brain barrier, neuroinflammation, oxidative stress, vasoconstriction, cerebral amyloid angiopathy, amyloid plaques, neurofibrillary tangles, and ultimately neuronal death. In addition, genetic factors such as post-ischemic changes in genetic programming in the expression of amyloid protein precursor, ß-secretase, presenilin-1 and -2, and tau protein play an important role in the irreversible progression of post-ischemic neurodegeneration. Since current treatment is aimed at preventing symptoms such as dementia and disability, the search for causative therapy that would be helpful in preventing and treating post-ischemic neurodegeneration of Alzheimer's disease proteinopathy is ongoing. Numerous studies have shown that the high contents of flavonoids and phenolic acids in honey have antioxidant, anti-inflammatory, anti-apoptotic, anti-amyloid, anti-tau protein, anticholinesterase, serotonergic, and AMPAK activities, influencing signal transmission and neuroprotective effects. Notably, in many preclinical studies, flavonoids and phenolic acids, the main components of honey, were also effective when administered after ischemia, suggesting their possible use in promoting recovery in stroke patients. This review provides new insight into honey's potential to prevent brain ischemia as well as to ameliorate damage in advanced post-ischemic brain neurodegeneration.

Honey for acute cough in children.

BACKGROUND: Cough causes concern for parents and is a major cause of outpatient visits. Cough can impact quality of life, cause anxiety, and affect sleep in children and their parents. Honey has been used to alleviate cough symptoms. This is an update of reviews previously published in 2014, 2012, and 2010. OBJECTIVES: To evaluate the effectiveness of honey for acute cough in children in ambulatory settings. SEARCH METHODS: We searched CENTRAL (2018, Issue 2), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (2014 to 8 February 2018), Embase (2014 to 8 February 2018), CINAHL (2014 to 8 February 2018), EBSCO (2014 to 8 February 2018), Web of Science (2014 to 8 February 2018), and LILACS (2014 to 8 February 2018). We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trial Registry Platform (WHO ICTRP) on 12 February 2018. The 2014 review included searches of AMED and CAB Abstracts, but these were not searched for this update due to lack of institutional access. SELECTION CRITERIA: Randomised controlled trials comparing honey alone, or in combination with antibiotics, versus no treatment, placebo, honey-based cough syrup, or other over-the-counter cough medications for children aged 12 months to 18 years for acute cough in ambulatory settings. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included six randomised controlled trials involving 899 children; we added three studies (331 children) in this update.We assessed two studies as at high risk of performance and detection bias; three studies as at unclear risk of attrition bias; and three studies as at unclear risk of other bias.Studies compared honey with dextromethorphan, diphenhydramine, salbutamol, bromelin (an enzyme from the Bromeliaceae (pineapple) family), no treatment, and placebo. Five studies used 7-point Likert scales to measure symptomatic relief of cough; one used an unclear 5-point scale. In all studies, low score indicated better cough symptom relief.Using a 7-point Likert scale, honey probably reduces cough frequency better than no treatment or placebo (no treatment: mean difference (MD) -1.05, 95% confidence interval (CI) -1.48 to -0.62; I² = 0%; 2 studies; 154 children; moderate-certainty evidence; placebo: MD -1.62, 95% CI -3.02 to -0.22; I² = 0%; 2 studies; 402 children; moderate-certainty evidence). Honey may have a similar effect as dextromethorphan in reducing cough frequency (MD -0.07, 95% CI -1.07 to 0.94; I² = 87%; 2 studies; 149 children; low-certainty evidence). Honey may be better than diphenhydramine in reducing cough frequency (MD -0.57, 95% CI -0.90 to -0.24; 1 study; 80 children; low-certainty evidence).Giving honey for up to three days is probably more effective in relieving cough symptoms compared with placebo or salbutamol. Beyond three days honey probably had no advantage over salbutamol or placebo in reducing cough severity, bothersome cough, and impact of cough on sleep for parents and children (moderate-certainty evidence). With a 5-point cough scale, there was probably little or no difference between the effects of honey and bromelin mixed with honey in reducing cough frequency and severity.Adverse events included nervousness, insomnia, and hyperactivity, experienced by seven children (9.3%) treated with honey and two children (2.7%) treated with dextromethorphan (risk ratio (RR) 2.94, 95% Cl 0.74 to 11.71; I² = 0%; 2 studies; 149 children; low-certainty evidence). Three children (7.5%) in the diphenhydramine group experienced somnolence (RR 0.14, 95% Cl 0.01 to 2.68; 1 study; 80 children; low-certainty evidence). When honey was compared with placebo, 34 children (12%) in the honey group and 13 (11%) in the placebo group complained of gastrointestinal symptoms (RR 1.91, 95% CI 1.12 to 3.24; I² = 0%; 2 studies; 402 children; moderate-certainty evidence). Four children who received salbutamol had rashes compared to one child in the honey group (RR 0.19, 95% CI 0.02 to 1.63; 1 study; 100 children; moderate-certainty evidence). No adverse events were reported in the no-treatment group. AUTHORS' CONCLUSIONS: Honey probably relieves cough symptoms to a greater extent than no treatment, diphenhydramine, and placebo, but may make little or no difference compared to dextromethorphan. Honey probably reduces cough duration better than placebo and salbutamol. There was no strong evidence for or against using honey. Most of the children received treatment for one night, which is a limitation to the results of this review. There was no difference in occurrence of adverse events between the honey and control arms.

Honey for acute cough in children.

BACKGROUND: Cough causes concern for parents and is a major cause of outpatient visits. It can impact on quality of life, cause anxiety and affect sleep in parents and children. Several remedies, including honey, have been used to alleviate cough symptoms. OBJECTIVES: To evaluate the effectiveness of honey for acute cough in children in ambulatory settings. SEARCH METHODS: We searched CENTRAL (2014, Issue 10), MEDLINE (1950 to October week 4, 2014), EMBASE (1990 to November 2014), CINAHL (1981 to November 2014), Web of Science (2000 to November 2014), AMED (1985 to November 2014), LILACS (1982 to November 2014) and CAB abstracts (2009 to January 2014). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing honey given alone, or in combination with antibiotics, versus nothing, placebo or other over-the-counter (OTC) cough medications to participants aged from one to 18 years for acute cough in ambulatory settings. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search results for eligible studies and extracted data on reported outcomes. MAIN RESULTS: We included three RCTs, two at high risk of bias and one at low risk of bias, involving 568 children. The studies compared honey with dextromethorphan, diphenhydramine, 'no treatment' and placebo for the effect on symptomatic relief of cough using a seven-point Likert scale. The lower the score, the better the cough symptom being assessed.Moderate quality evidence showed that honey may be better than 'no treatment' in reducing the frequency of cough (mean difference (MD) -1.05; 95% confidence interval (CI) -1.48 to -0.62; I(2) statistic 23%; two studies, 154 participants). High quality evidence also suggests that honey may be better than placebo for reduction of cough frequency (MD -1.85; 95% Cl -3.36 to -0.33; one study, 300 participants). Moderate quality evidence suggests that honey does not differ significantly from dextromethorphan in reducing cough frequency (MD -0.07; 95% CI -1.07 to 0.94; two studies, 149 participants). Low quality evidence suggests that honey may be slightly better than diphenhydramine in reducing cough frequency (MD -0.57; 95% CI -0.90 to -0.24; one study, 80 participants).Adverse events included mild reactions (nervousness, insomnia and hyperactivity) experienced by seven children (9.3%) from the honey group and two (2.7%) from the dextromethorphan group; the difference was not significant (risk ratio (RR) 2.94; 95% Cl 0.74 to 11.71; two studies, 149 participants). Three children (7.5%) in the diphenhydramine group experienced somnolence (RR 0.14; 95% Cl 0.01 to 2.68; one study, 80 participants). When honey was compared with placebo, four children (1.8%) in the honey group and one (1.3%) from the placebo group complained of gastrointestinal symptoms (RR 1.33; 95% Cl 0.15 to 11.74). However, there was no significant difference between honey versus dextromethorphan, honey versus diphenhydramine or honey versus placebo. No adverse event was reported in the 'no treatment' group. AUTHORS' CONCLUSIONS: Honey may be better than 'no treatment', diphenhydramine and placebo for the symptomatic relief of cough, but it is not better than dextromethorphan. None of the included studies assessed the effect of honey on 'cough duration' because intervention and follow-up were for one night only. There is no strong evidence for or against the use of honey.

Medical honey and its role in paediatric patients.

BACKGROUND: The use of complementary medical treatment in wound management has continued to grow throughout the world. There is a large body of evidence that supports the use of honey as a wound dressing for a wide range of wound types. The authors present an update of present knowledge about honey as a form of complementary medicine in paediatric wound management. METHODS: The literature cited was found by searching the PubMed, BIOSIS and ISI Web of Science databases for the phrase 'honey and wound'. Papers where honey was used in a mixture with other therapeutic substances were excluded. Randomised controlled trials as well as case studies were taken into consideration. RESULTS: This paper reviews data on the effectiveness of honey in wound healing; 80 citations or references were found that matched the criteria. Furthermore, the wound-healing properties of honey are described and the mechanism of action discussed. The authors' data show that honey induced enhanced epithelialisation, minimised scar formations and had an anti-microbiotic effect. CONCLUSION: These results should encourage the use of medical honey in the field of paediatrics. It is a safe and natural substance that induces wound healing at a greater rate than conventional methods.

Live bee acupuncture (Bong-Chim) dermatitis: dermatitis due to live bee acupuncture therapy in Korea.

Live bee acupuncture (Bong-Chim) dermatitis is an iatrogenic disease induced by so-called live bee acupuncture therapy, which applies the honeybee (Apis cerana) stinger directly into the lesion to treat various diseases in Korea. We present two cases of live bee acupuncture dermatitis and review previously published articles about this disease. We classify this entity into three stages: acute, subacute, and chronic. The acute stage is an inflammatory reaction, such as anaphylaxis or urticaria. In the chronic stage, a foreign body granuloma may develop from the remaining stingers, similar to that of a bee sting reaction. However, in the subacute stage, unlike bee stings, we see the characteristic histological "flame" figures resulting from eosinophilic stimulation induced by excessive bee venom exposure. We consider this stage to be different from the adverse skin reaction of accidental bee sting.

Honey for acute cough in children.

BACKGROUND: Cough causes concern for parents and is a major cause of outpatient visits. It can impact on quality of life, cause anxiety and affect sleep in parents and children. Several remedies, including honey, have been used to alleviate cough symptoms. OBJECTIVES: To evaluate the effectiveness of honey for acute cough in children in ambulatory settings. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2011) which contains the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (1950 to December week 4, 2011); EMBASE (1990 to January 2012); CINAHL (1981 to January 2012); Web of Science (2000 to January 2012); AMED (1985 to January 2012); LILACS (1982 to January 2012); and CAB abstracts (2009 to January 2012). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing honey given alone, or in combination with antibiotics, versus nothing, placebo or other over-the-counter (OTC) cough medications to participants aged from two to 18 years for acute cough in ambulatory settings. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search results for eligible studies and extracted data on reported outcomes. MAIN RESULTS: We included two RCTs of high risk of bias involving 265 children. The studies compared the effect of honey with dextromethorphan, diphenhydramine and 'no treatment' on symptomatic relief of cough using the 7-point Likert scale.Honey was better than 'no treatment' in reducing frequency of cough (mean difference (MD) -1.07; 95% confidence interval (CI) -1.53 to -0.60; two studies; 154 participants). Moderate quality evidence suggests honey did not differ significantly from dextromethorphan in reducing cough frequency (MD -0.07; 95% CI -1.07 to 0.94; two studies; 149 participants). Low quality evidence suggests honey may be slightly better than diphenhydramine in reducing cough frequency (MD -0.57; 95% CI -0.90 to -0.24; one study; 80 participants).Adverse events included mild reactions (nervousness, insomnia and hyperactivity) experienced by seven children (9.3%) from the honey group and two (2.7%) from the dextromethorphan group; the difference was not significant (risk ratio (RR) 2.94; 95% Cl 0.74 to 11.71; two studies; 149 participants). Three children (7.5%) in the diphenhydramine group experienced somnolence (RR 0.14; 95% Cl 0.01 to 2.68; one study; 80 participants) but there was no significant difference between honey versus dextromethorphan or honey versus diphenhydramine. No adverse event was reported in the 'no treatment' group. AUTHORS' CONCLUSIONS: Honey may be better than 'no treatment' and diphenhydramine in the symptomatic relief of cough but not better than dextromethorphan. There is no strong evidence for or against the use of honey.

Parents' and primary healthcare practitioners' perspectives on the safety of honey and other traditional paediatric healthcare approaches.

BACKGROUND: Traditional and complementary healthcare approaches (TCA) are widely used for children, often because of perceived safety. Honey is a traditional remedy for upper respiratory tract symptoms in infants. Health officials currently advise limiting honey use because of the risk of botulism. OBJECTIVE: This paper discusses honey as a traditional healthcare approach for children in a multi-ethnic community, and parents' and primary healthcare practitioners' (PHPs) perceptions of its safety. DESIGN: As part of a larger study exploring beliefs about TCA, this paper focuses on perceived safety and use of honey, using data extracted for detailed analysis. Eleven parent focus groups (n= 92) and 30 interviews with PHPs were conducted. Qualitative data analysis used the Framework approach. SETTING: London Boroughs of Brent and Harrow RESULTS: TCA, particularly home remedies, dietary and religious approaches were popular for children. Honey was a particularly common TCA, reportedly used by 27 (29%) parents for their children. Honey was believed to be traditional, acceptable, accessible, natural and safe. It was most commonly used for respiratory tract symptoms and administered with hot water and lemon juice. PHPs were more concerned about the safety of TCA than parents. Almost half (40%) of PHPs mentioned the use of honey for children, few perceived it as a 'treatment' or were concerned about botulism. Others were aware of the risks and some reported challenges in communicating risk to parents. CONCLUSION: TCA are commonly used for children, honey in particular for respiratory tract symptoms. Parents and some PHPs appear unaware of the risk of botulism from honey use in infants. Healthcare practitioners should ask routinely about the use of honey and other TCA, and consider different parental belief systems in ethnically diverse populations. Further research is required on the use and efficacy of honey for infants, to raise awareness of its benefits and risks.

In vivo activity assessment of a "honey-bee pollen mix" formulation.

Honey-bee pollen mix (HBM) formulation is claimed to be effective for the treatment of asthma, bronchitis, cancers, peptic ulcers, colitis, various types of infections including hepatitis B, and rheumatism by the herb dealers in northeast Turkey. In the present study, in vivo antinociceptive, anti-inflammatory, gastroprotective and antioxidant effects of pure honey and HBM formulation were evaluated comparatively. HBM did not show any significant gastroprotective activity in a single administration at 250 mg/kg dose, whereas a weak activity was observed after three days of successive administration at 500 mg/kg dose. On the other hand, HBM displayed significant antinociceptive (p <0.01) and anti-inflammatory (p <0.01) activities at 500 mg/kg dose orally without inducing any apparent acute toxicity or gastric damage. HBM was also shown to possess potent antilipidperoxidant activity (p <0.01) at 500 mg/kg dose against acetaminophen-induced liver necrosis model in mice. On the other hand, pure honey did not exert any remarkable antinociceptive, anti-inflammatory and gastroprotective activity, but a potent antilipidperoxidant activity (p <0.01) was determined. Results have clearly proved that mixing pure honey with bee pollen significantly increased the healing potential of honey and provided additional support for its traditional use. Total phenolic and flavonoid contents of HBM were found to be 145 and 59.3 mg/100 g of honey, which were estimated as gallic acid and quercetin equivalents, respectively.