L-Amygdalin

Amygdalin epimers exert discrepant anti-pulmonary fibrosis activity via inhibiting TGF-beta1/Smad2/3 pathway.[Pubmed:37364767]

Pulm Pharmacol Ther. 2023 Aug;81:102230.

Idiopathic pulmonary fibrosis (IPF) represents a chronic and progressive tissue repair response that leads to irreversible scarring and lung remodeling. The decoction of bitter almond usually contains amygdalin epimers in traditional clinical application for lung disease. To reveal the differences of cytotoxicity and antifibrotic effect between amygdalin epimers, and potential mechanism is also explored. The cytotoxicity of amygdalin epimers were evaluated with MRC-5 cells in vitro. Their antifibrotic activities were evaluated in bleomycin-induced C57BL/6 mice and TGF-beta1-induced MRC-5 cells. Here we demonstrated that L-Amygdalin is more toxic of the amygdalin epimers in MRC-5 cells, and D-amygdalin is more effective in anti-pulmonary fibrosis among the amygdalin epimers in bleomycin-induced C57BL/6 mice. Herein, it was observed that D-amygdalin had a stronger inhibitory effect on inflammation than L-Amygdalin, and had similar results in inhibiting the mRNA and protein expression levels of fibrosis-related biomarkers. The mechanism of anti-pulmonary fibrosis showed that amygdalin epimers suppressing expression of phosphorylation of Smads2/3, which implying deactivation of the TGF-beta1induced Smads2/3 signal pathway. This study evaluates the amygdalin epimers cytotoxicity and antifibrotic effect, and its mechanisms were related to the TGF-beta1/Smads2/3 signal pathway. It provides a reference for clinical safety and effectiveness of amygdalin epimers.

[Evaluation of key production processes of Chan Taoren formula granules based on characteristic chromatogram and D-amygdalin transfer rate].[Pubmed:31872659]

Zhongguo Zhong Yao Za Zhi. 2019 Nov;44(21):4641-4647.

This study aimed to establish characteristic chromatogram and content determination method for Chan Taoren formula granules,evaluate the production processes of Chan Taoren formula granules based on the correlation of characteristic chromatogram and the transfer rate of D-amygdalin,and clarify the key control points. The optimized analytical method was carried out on a Waters CORTECS C18 column(4. 6 mmx150 mm,2. 7 mum) with acetonitrile-0. 1% phosphoric acid aqueous solution as the mobile phase at a flow rate of 0. 6 m L.min-1. The detection wavelength was 207 nm,and the column temperature was 20 ℃ ． As compared with the standard decoction of Chan Taoren,there were five characteristic peaks in the decoction pieces,extracts,concentrates,spray-dried powders and formula granules,basically consistent in relative retention time and peak pattern; in addition,the transfer rate of D-amygdalin from Chan Taoren pieces to the formula granules was within the transfer rate range of standard decoction. The average transfer rate of D-amygdalin was 56.65%,72.85%,94.58% and 99.29% respectively in the extraction,concentration,spray drying and granulation processes. Therefore,the factors affecting D-amygdalin in the extraction process were further studied. The results showed that D-amygdalin was easily converted to L-Amygdalin in the water extraction process,leading to a low transfer rate of D-amygdalin in this process.D-amygdalin was unstable under alkaline conditions and prone to isomerization. Both liquid to solid ratio and extraction time had significant effects on the extraction rate of D-amygdalin. In this study,the key links in the production process of Chan Taoren formula granules was clarified based on the characteristic chromatogram and the quantity transmission of D-amygdalin,which provided a theoretical basis for production and quality control.

Changes of amygdalin and volatile components of apricot kernels during the ultrasonically-accelerated debitterizing.[Pubmed:31450302]

Ultrason Sonochem. 2019 Nov;58:104614.

Ultrasound has been regarded as an efficient novel technique for debitterizing of the apricot kernels, but its influence is severely concerned on the possible epimerization of d-amygdalin to the L-Amygdalin, a more potentially toxigenic compound. Considering this, the experiments were conducted to investigate the epimerization of d-amygdalin and the volatile components in the debitterizing water, which were separated and identified by the high performance liquid chromatography (HPLC) and gas chromatography with a mass spectrometer (GC-MS), respectively. The results indicate that the ultrasonically-debitterizing did not cause the epimerization of d-amygdalin to the L-Amygdalin, while the procedure can be greatly accelerated due to the rapid mass transfer and degradation of d-amygdalin induced by ultrasound irradiation. In addition, the water from the ultrasonically-debitterizing of apricot kernels exerted more aromas compared with that of the conventional debitterizing, which might have more applications about this kind of water. In a word, ultrasound can be safely applied in the debitterizing industry of apricot kernels.

Stereoselective metabolism of amygdalin-based study of detoxification of Semen Armeniacae Amarum in the Herba Ephedrae-Semen Armeniacae Amarum herb pair.[Pubmed:26719286]

J Ethnopharmacol. 2016 Feb 17;179:356-66.

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 beta-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.

A simple method for the estimation of amygdalin in the urine.[Pubmed:566946]

Res Commun Chem Pathol Pharmacol. 1978 May;20(2):367-78.

A procedure for the estimation of D- and D,L-Amygdalin in urine is described. Amygdalin is hydrolyzed by beta-glucosidase and base to benzaldehyde, glucose and cyanide. Benzaldehyde is extracted with methylene chloride and the ultraviolet (UV) absorbence determined at 243 nm. The response of human urine "spiked" with amygdalin was linear between 10 and 75 microgram/ml. Mice administered 100 mg/kg of amygdalin intravenously or orally excreted about 70 and 20% of the administered dose, respectively, over 96 hours. In each instance more than 96% of excreted drug equivalents were obtained within the first 24 hours.