Amygdalin - A pharmacological and toxicological review.

ETHNOPHARMACOLOGICAL RELEVANCE: Amygdalin is commonly distributed in plants of the Rosaceae, such as peach, plum, loquat, apple and bayberry, but most notably in the seeds (kernels) of apricot almonds. As a naturally aromatic cyanogenic compound, it has long been used in Asia, Europe and other regions for the treatment of various diseases including cough, asthma, nausea, leprosy and leukoderma. Importantly, in recent years, an increasing attention has been paid to its antitumor effect. AIM OF THE STUDY: The paper aims to review the pharmacological activities and toxicological effects of amygdalin and provide a reference and perspective for its further investigation. METHODS: Electronic databases including the Web of Science, Cochrane Library, PubMed, EMBASE, the Chinese Biological Medicine Database, China National Knowledge Infrastructure, Wanfang database and VIP information database were searched up to November 2019 to identify eligible studies. A meticulous review was performed, an in-depth analysis on the pharmacological activity and toxicology of amygdalin was conducted, and perspectives for future research were also discussed. RESULTS: A total of 110 papers about in vitro/in vivo studies on amygdalin have been reviewed. Analysis on the data suggested that this compound presented pharmacological activities of anti-tumor, anti-fibrotic, anti-inflammatory, analgesic, immunomodulatory, anti-atherosclerosis, ameliorating digestive system and reproductive system, improving neurodegeneration and myocardial hypertrophy, as well as reducing blood glucose. In addition, studies revealed that amygdalin's toxicity was caused by its poisonous decomposite product of benzaldehyde and hydrogen cyanide after oral ingestion, toxicity of intravenous administration route was far less than the oral route, and it can be avoidable with an oral dose ranging from 0.6 to 1 g per day. CONCLUSION: This paper has systematically reviewed the pharmacology and toxicology of amygdalin and provided comprehensive information on this compound. We hope this review highlights some perspectives for the future research and development of amygdalin.

Effect of Natural ß-Glucosidase Inhibitors in Reducing Toxicity of Amygdalin in Persicae Semen.

Amygdalin can be decomposed into hydrocyanic acid, which is the primary source of Persicae Semen toxicity, by gut flora. Here, the inhibitory activity of ß-glucosidase for test herb extracts was first determined and compared. In turn, optimization of the ratio of substrate and inhibitor in vitro and LD50 values of extracts, serum and liver contents of amygdalin in vivo was measured. Lycii Cortex was found to be the best inhibitory activity for ß-glucosidase. The ratio of amygdalin-to-Lycii Cortex extract of 7.19:8.18 (mmol L-1 /mg mL-1 ) can be relatively suitable for inhibiting ß-glucosidase activity in test in vitro reaction system. After mixed with Lycii Cortex extract, the toxicity of Persicae Semen ethanol extract in mice is significantly reduced and more amygdalin can be absorbed into the bloodstream. The study provides useful information for reducing toxicity of Persicae Semen and suggests how to better use these natural ß-glucosidase inhibitors in the utilization of glycosides and aglycones. Copyright © 2017 John Wiley & Sons, Ltd.

Stereoselective metabolism of amygdalin-based study of detoxification of Semen Armeniacae Amarum in the Herba Ephedrae-Semen Armeniacae Amarum herb pair.

ETHNOPHARMACOLOGICAL RELEVANCE: The Mahuang-Xingren (MX) herb pair, the combination of Herba Ephedrae (Mahuang in Chinese) and Semen Armeniacae Amarum (Xingren in Chinese), is a core component of traditional Chinese medicine formulations used to treat asthma and bronchitis. Although Xingren is considered to be toxic, MX is widely used in the clinic and has few adverse effects. The mechanism underlying detoxification of Xingren by Mahuang in MX remains unknown and merits investigation. AIM OF THE STUDY: To determine the mechanism underlying detoxification of Xingren by Mahuang in MX. MATERIALS AND METHODS: Acute toxic effects were evaluated in mice after oral administration of Mahuang, Xingren, and MX aqueous extracts. Synergism, additivity, and antagonism were quantified by determining the CI (combination index) and DRI (dose-reduction index), which were calculated by the median effect method. High performance liquid chromatography analysis of bioactive compounds (ephedrine, pseudoephedrine and amygdalin) in aqueous extracts and data from previous pharmacokinetic studies in rats were combined to explore the potential mechanism of toxicity antagonism by the components of MX. Moreover, the cytotoxic effects of amygdalin and amygdalin activated by ß-glucosidase (including different proportions of l-amygdalin and d-amygdalin) were also investigated. RESULTS: Mahuang prevented and antagonized the acute toxicity of Xingren and allowed escalation of the Xingren dose. Pearson correlation analysis indicated that the proportion of d-amygdalin was closely correlated with the antagonism of Xingren toxicity. The antagonism of its acute toxicity was primarily attributed to stereoselective metabolism of amygdalin. Interestingly, the process was facilitated by Mahuang, which led to reduced levels of the d-prunasin in vivo and thus reduced toxicity. Furthermore, the mechanism was also evaluated by testing the cytotoxicity of amygdalin. Metabolism of d-amygdalin was a major cause of cytotoxicity and no stereoselective metabolism occurred in culture medium. CONCLUSIONS: A comprehensive study of Xingren detoxification in the context of the MX combination suggested that stereoselective metabolism of amygdalin facilitated by Mahuang may be the crucial mechanism underlying detoxification of Xingren in the MX combination. Therefore, Mahuang acts to enhance and control the effects of Xingren in the MX combination. These results illustrate the rationale behind the combination of Mahuang and Xingren.

[Accidental poisoning with peach seeds used as anticancer therapy--report of two cases]. / Przypadkowe zatrucie pestkami brzoskwini stosowanymi w celach przeciwnowotworowych--opis dwóch przypadków.

UNLABELLED: We described two cases of poisoning with amygdalin. Clinical signs presented by two females were mild and lasted up to 5 hours. CONCLUSIONS: The usage of amygdalin may be connected with serious side effects. The cyanide and prussic acid which are deliberated in digestive system are responsible for toxicity in such cases. The rarity of poisoning with amygdalin as well as high cost of analysis are responsible for the reason that most labs are not prepare for such procedure.

Amygdalin toxicity studies in rats predict chronic cyanide poisoning in humans.

Significant amounts of cyanide are released when amygdalin (Laetrile), a cyanogenic glycoside, is given orally or intravenously to rats. The amount of cyanide liberated following oral administration is dependent in part on the bacterial flora of the gut and can be suppressed by antibiotic pretreatment of the animals. Bacteria from human feces likewise hydrolyze amygdalin with release of cyanide. Humans taking amygdalin orally in the hope of preventing cancer are likely to be exposed to levels of cyanide in excess of that associated with the development of tropical ataxic neuropathy in people of underdeveloped countries where food containing cyanogenic glycosides is a staple part of the diet.

Laetrile toxicity studies in dogs.

Dogs were fed laetrile and fresh, sweet almonds under various conditions. The doses of laetrile were similar to those prescribed for patients with cancer and ranged on a basis of gram to square meter from an equivalent of the oral dose for man to five times this dose. Six of the ten dogs died of cyanide poisoning. One dog recovered, and three dogs, at the time of sacrifice, demonstrated various levels of neurologic impairment, ranging from difficulty in walking to coma. These studies demonstrate that oral laetrile is highly toxic when taken with some common table foods. We predict that there will be an increased incidence of cyanide poisoning in man as laetrile becomes more readily available.