Honey bee colonies change their foraging decisions after in-hive experiences with unsuitable pollen.

Pollen is the protein resource for Apis mellifera and its selection affects colony development and productivity. Honey bee foragers mainly lose their capacity to digest pollen, so we expect that those pollen constituents that can only be evaluated after ingestion will not influence their initial foraging preferences at food sources. We predicted that pollen composition may be evaluated in a delayed manner within the nest, for example, through the effects that the pollen causes on the colony according to its suitability after being used by in-hive bees. To address whether pollen foraging is mediated by in-hive experiences, we conducted dual-choice experiments to test the avoidance of pollen adulterated with amygdalin, a deterrent that causes post-ingestion malaise. In addition, we recorded pollen selection in colonies foraging in the field after being supplied or not with amygdalin-adulterated pollen from one of the dominant flowering plants (Diplotaxis tenuifolia). Dual-choice experiments revealed that foragers did not avoid adulterated pollens at the foraging site; however, they avoided pollen that had been offered adulterated within the nest on the previous days. In field experiments, pollen samples from colonies supplied with amygdalin-adulterated pollen were more diverse than controls, suggesting that pollen foraging was biased towards novel sources. Our findings support the hypothesis that pollen assessment relies on in-hive experiences mediated by pollen that causes post-ingestive malaise.

Recent trends in nanoparticulate delivery system for amygdalin as potential therapeutic herbal bioactive agent for cancer treatment.

Cancer is the deadliest and most serious health problem. The mortality rate of cancer patients has increased significantly worldwide in recent years. There are several treatments available, but these treatments have many limitations, such as non-specific targeting, toxicity, bioavailability, solubility and permeability problems, serious side effects, and a higher dose. Many people prefer phytomedicine because it has fewer side effects. However, amygdalin is a naturally occurring phytoconstituent. It has many harmful effects due to the cyanide group present in the chemical structure. Many scientists and researchers have given their thoughts associated with amygdalin and its toxicities. However, there is a need for a more advanced, effective, and newer delivery system for amygdalin to reduce its toxic effect. Nanotechnology has become a more refined and emerging medical approach, offering innovative ways to treat cancer. This review focuses on the use of amygdaline as herbal medicine encapsulating into several nanoparticulate delivery systems such as silver nanoparticles, graphene oxide nanoparticles, gold nanoparticles, nanofibers, nanocomposites, niosomes, and magnetic nanoparticles in the treatment of cancer. In addition, this article provides information on amygdalin structure and physical properties, pharmacokinetics, toxicity, and challenges with amygdalin.

TMT-Based Proteomics Reveal the Mechanism of Action of Amygdalin against Rheumatoid Arthritis in a Rat Model through Regulation of Complement and Coagulation Cascades.

The limitations of current medications for treating rheumatoid arthritis (RA) emphasize the urgent need for the development of new drugs. This study aimed to investigate the potential anti-RA mechanism of amygdalin using tandem mass tag (TMT)-based quantitative proteomics technology. First, the anti-RA activity of amygdalin was evaluated in a Complete Freund's adjuvant (CFA)-induced rat model. Then, the roles and importance of proteins in the extracted rat joint tissue were evaluated using TMT-based quantitative proteomics technology. A bioinformatics analysis was used to analyze differentially abundant proteins (DAPs). A proteomics analysis identified 297 DAPs in the amygdalin group compared with the model group, of which 53 upregulated proteins and 51 downregulated proteins showed opposite regulatory trends to the DAPs produced after modeling. According to enrichment analyses of the DAPs, the signaling pathways with a high correlation degree were determined to be the complement and coagulation cascades. Furthermore, western blotting and molecular docking were used to further validate the key node proteins, e.g., complement C1s subcomponent (C1s), component C3 (C3) and kininogen 1 (Kng1). These results suggest that amygdalin may be a promising agent for treating RA by regulating the complement and coagulation cascades.

Effectiveness of natural biomaterials in the protection and healing of experimentally induced gastric mucosa Ulcer in rats.

BACKGROUND: A gastric ulcer is a painful lesion of the gastric mucosa that can be debilitating or even fatal. The effectiveness of several plant extracts in the therapy of this illness has been demonstrated in traditional pharmacopoeias. AIM: this study was aimed to see if propolis, ginseng in normal or nano form, and amygdalin might help in preventing the ulcerative effects of absolute ethanol. METHODS: Gastroprotective properties of pretreatments before ethanol gavage in rats were compared to omeprazole. The ulcer and stomach parameters (ulcerated regions) were measured (mm2), ulcer inhibition percentage, the stomachs were assessed macroscopically with gastric biopsy histological examinations. RESULTS: Amygdalin, normal and nano ginseng, nano propolis followed by propolis all showed great efficacy in protecting the cyto-architecture and function of the gastric mucosa. The number of ulcerated sites was greatly reduced, and the percentage of stomach protection was increased. Histopathological examination had confirmed great protective effects of the nanoformulations followed by amygdalin. The protection and healing rate was completed to about 100% in all tested materials while ulcer areas were still partially unhealed in normal propolis and omeprazole. Quantitative assay of the m-RNA levels Enothelin 1(ET-1), leukotriene4 (LT-4), and caspase 3(Cas-3) genes and Histamine were done and revealed significant up-regulations in ethanol group and the maximum protective effect was reported with ginseng nano, moreover the histamine content was significantly decreased with nano- formulated extracts. CONCLUSION: Amygdalin and the nanoformulated ginseng and propolis had exhibited a marked protective effect against the ulcerative toxic effects of ethanol.

Amygdalin as a Promising Anticancer Agent: Molecular Mechanisms and Future Perspectives for the Development of New Nanoformulations for Its Delivery.

Cancer rates are increasing, and cancer is one of the main causes of death worldwide. Amygdalin, also known as vitamin B17 (and laetrile, a synthetic compound), is a cyanogenic glycoside compound that is mainly found in the kernels and pulps of fruits. This compound has been proposed for decades as a promising naturally occurring substance which may provide anticancer effects. This is a comprehensive review which critically summarizes and scrutinizes the available studies exploring the anticancer effect of amygdalin, highlighting its potential anticancer molecular mechanisms as well as the need for a nontoxic formulation of this substance. In-depth research was performed using the most accurate scientific databases, e.g., PubMed, Cochrane, Embase, Medline, Scopus, and Web of Science, applying effective, characteristic, and relevant keywords. There are several pieces of evidence to support the idea that amygdalin can exert anticancer effects against lung, breast, prostate, colorectal, cervical, and gastrointestinal cancers. Amygdalin has been reported to induce apoptosis of cancer cells, inhibiting cancer cells' proliferation and slowing down tumor metastatic spread. However, only a few studies have been performed in in vivo animal models, while clinical studies remain even more scarce. The current evidence cannot support a recommendation of the use of nutritional supplements with amygdalin due to its cyano-moiety which exerts adverse side effects. Preliminary data have shown that the use of nanoparticles may be a promising alternative to enhance the anticancer effects of amygdalin while simultaneously reducing its adverse side effects. Amygdalin seems to be a promising naturally occurring agent against cancer disease development and progression. However, there is a strong demand for in vivo animal studies as well as human clinical studies to explore the potential prevention and/or treatment efficiency of amygdalin against cancer. Moreover, amygdalin could be used as a lead compound by effectively applying recent developments in drug discovery processes.

Isomerization and Stabilization of Amygdalin from Peach Kernels.

In this study, isomerization conditions, cytotoxic activity, and stabilization of amygdalin from peach kernels were analyzed. Temperatures greater than 40 °C and pHs above 9.0 resulted in a quickly increasing isomer ratio (L-amygdalin/D-amygdalin). At acidic pHs, isomerization was significantly inhibited, even at high temperature. Ethanol inhibited isomerization; the isomer rate decreased with the ethanol concentration increasing. The growth-inhibitory effect on HepG2 cells of D-amygdalin was diminished as the isomer ratio increased, indicating that isomerization reduces the pharmacological activity of D-amygdalin. Extracting amygdalin from peach kernels by ultrasonic power at 432 W and 40 °C in 80% ethanol resulted in a 1.76% yield of amygdalin with a 0.04 isomer ratio. Hydrogel beads prepared by 2% sodium alginate successfully encapsulated the amygdalin, and its encapsulation efficiency and drug loading rate reached 85.93% and 19.21%, respectively. The thermal stability of amygdalin encapsulated in hydrogel beads was significantly improved and reached a slow-release effect in in vitro digestion. This study provides guidance for the processing and storage of amygdalin.

Antioxidant, Anti-Inflammatory, and Anti-Cancer Properties of Amygdalin Extracted from Three Cassava Varieties Cultivated in Benin.

Given that cancer is a disease that is rampant in the world and especially in Africa, where the population has enormous difficulty treating it, plants are a safer and less expensive alternative. Cassava is a plant species valued in Benin because of its numerous medicinal and nutritional virtues. This study evaluated the biological activities of amygdalin from the organs of three cassava varieties most commonly produced in Benin (BEN, RB, and MJ). HPLC analysis was used to quantify amygdalin in cassava organs and derivatives. Phytochemical screening was performed to determine secondary metabolite groups. DPPH and FRAP methods were used to assess antioxidant activity. Cytotoxicity of the extracts was tested on Artemia salina larvae. The anti-inflammatory activity was evaluated in vivo in an albino mouse paw edema model induced by 5% formalin. The anticancer activity was evaluated in vivo on Wistar rats rendered cancerous by 1,2-dimethylhydrazine (DMH) using 5-fluorouracil as a reference molecule. The results showed that the organs of all three-cassava varieties contained glycosides, flavonoids, saponosides, steroids, tannins, coumarins, and cyanogenic derivatives. Young stems and fresh cassava leaves had the highest amygdalin concentrations, with 11,142.99 µg 10 g-1 and 9251.14 µg 10 g-1, respectively. The Agbeli derivative was more concentrated in amygdalin, with a content of 401.56 µg 10 g-1 than the other derivatives. The antioxidant activity results showed that the amygdalin extracts were DPPH radical scavengers with IC50 values ranging from 0.18 mg mL-1 to 2.35 mg mL-1. The cytotoxicity test showed no toxicity of the extracts toward shrimp larvae. Administration of amygdalin extracts from the leaves of BEN and MJ varieties prevents inflammatory edema. The percentages of edema inhibition varied between 21.77% and 27.89%. These values are similar (p > 0.05) to those of acetylsalicylic acid (25.20%). Amygdalin extract of the BEN variety significantly (p < 0.0001) reduces edema. Both BEN extracts inhibited cancer induction with DMH. In preventive and curative treatments, rats fed with amygdalin extracts showed low anti-cancer activity under the effect of DMH and a significant difference in biochemical results. Thus, the organs of all three cassava varieties studied have secondary metabolites and good antioxidant activity. The leaves contain high levels of amygdalin and can be used as anti-inflammatory and anticancer agents.

Synergy in symbiosis.

Honeybees rely on their microbial gut symbionts to overcome a potent toxin found in pollen and nectar.

Phytochemistry and pharmacology of Armeniacae semen Amarum: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Armeniacae Semen Amarum (Prunus armeniaca L. var. ansu Maxim., Ku xingren, bitter almond, ASA) is an important medicine in Traditional Chinese Medicine (TCM). It is widely used because of its remarkable curative effect in relieving cough and asthma, moistening intestines and defecating. AIM OF THE REVIEW: This review aims to enlighten the deeper knowledge about ASA, giving a comprehensive overview of its traditional uses, phytochemistry, pharmacology and toxicology for future investigation of plant-based drugs and therapeutic applications. MATERIALS AND METHODS: The databases used are Web of Science, PubMed, Baidu academic, Google academic, CNKI, Wanfang and VIP . In addition, detailed information on ASA was obtained from relevant monographs such as Chinese Pharmacopoeia. RESULTS: The active components of ASA mainly include amygdalin, bitter almond oil, essential oil, protein, vitamin, trace elements and carbohydrates. The pharmacological studies have shown that ASA has beneficial effects such as antitussive, antiasthmatic, anti-inflammatory, analgesic, antioxidant, antitumour, cardioprotective, antifibrotic, immune regulatory, bowel relaxation, insecticidal, etc. CONCLUSIONS: Many reports have been published on ASA's various active ingredients and biological uses. However, only a few reviews on its phytoconstituents and pharmacological uses. In addition, the exploration and development of ASA in other fields also deserve more attention in future research.

Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-ß/Smad Signaling.

OBJECTIVE: To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model, and the underlying mechanisms were partly dissected in vivo and in vitro. METHODS: Thirty-two male mice were randomly divided into 4 groups, including control, model, low- and high-dose amygdalin-treated groups, 8 mice in each group. Except the control group, mice in the other groups were injected intraperitoneally with 10% carbon tetrachloride (CCl4)-olive oil solution 3 times a week for 6 weeks to induce liver fibrosis. At the first 3 weeks, amygdalin (1.35 and 2.7 mg/kg body weight) were administered by gavage once a day. Mice in the control group received equal quantities of subcutaneous olive oil and intragastric water from the fourth week. At the end of 6 weeks, liver tissue samples were harvested to detect the content of hydroxyproline (Hyp). Hematoxylin and eosin and Sirius red staining were used to observe the inflammation and fibrosis of liver tissue. The expressions of collagen I (Col-I), alpha-smooth muscle actin (α-SMA), CD31 and transforming growth factor ß (TGF-ß)/Smad signaling pathway were observed by immunohistochemistry, quantitative real-time polymerase chain reaction and Western blot, respectively. The activation models of hepatic stellate cells, JS-1 and LX-2 cells induced by TGF-ß1 were used in vitro with or without different concentrations of amygdalin (0.1, 1, 10 µmol/L). LSECs. The effect of different concentrations of amygdalin on the expressions of liver sinusoidal endothelial cells (LSECs) dedifferentiation markers CD31 and CD44 were observed. RESULTS: High-dose of amygdalin significantly reduced the Hyp content and percentage of collagen positive area, and decreased the mRNA and protein expressions of Col-I, α-SMA, CD31 and p-Smad2/3 in liver tissues of mice compared to the model group (P<0.01). Amygdalin down-regulated the expressions of Col-I and α-SMA in JS-1 and LX-2 cells, and TGFß R1, TGFß R2 and p-Smad2/3 in LX-2 cells compared to the model group (P<0.05 or P<0.01). Moreover, 1 and 10 µmol/L amygdalin inhibited the mRNA and protein expressions of CD31 in LSECs and increased CD44 expression compared to the model group (P<0.05 or P<0.01). CONCLUSIONS: Amygdalin can dramatically alleviate liver fibrosis induced by CCl4 in mice and inhibit TGF-ß/Smad signaling pathway, consequently suppressing HSCs activation and LSECs dedifferentiation to improve angiogenesis.

Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-β/Smad Signaling / 中国结合医学杂志

OBJECTIVE@#To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model, and the underlying mechanisms were partly dissected in vivo and in vitro.@*METHODS@#Thirty-two male mice were randomly divided into 4 groups, including control, model, low- and high-dose amygdalin-treated groups, 8 mice in each group. Except the control group, mice in the other groups were injected intraperitoneally with 10% carbon tetrachloride (CCl4)-olive oil solution 3 times a week for 6 weeks to induce liver fibrosis. At the first 3 weeks, amygdalin (1.35 and 2.7 mg/kg body weight) were administered by gavage once a day. Mice in the control group received equal quantities of subcutaneous olive oil and intragastric water from the fourth week. At the end of 6 weeks, liver tissue samples were harvested to detect the content of hydroxyproline (Hyp). Hematoxylin and eosin and Sirius red staining were used to observe the inflammation and fibrosis of liver tissue. The expressions of collagen I (Col-I), alpha-smooth muscle actin (α-SMA), CD31 and transforming growth factor β (TGF-β)/Smad signaling pathway were observed by immunohistochemistry, quantitative real-time polymerase chain reaction and Western blot, respectively. The activation models of hepatic stellate cells, JS-1 and LX-2 cells induced by TGF-β1 were used in vitro with or without different concentrations of amygdalin (0.1, 1, 10 µmol/L). LSECs. The effect of different concentrations of amygdalin on the expressions of liver sinusoidal endothelial cells (LSECs) dedifferentiation markers CD31 and CD44 were observed.@*RESULTS@#High-dose of amygdalin significantly reduced the Hyp content and percentage of collagen positive area, and decreased the mRNA and protein expressions of Col-I, α-SMA, CD31 and p-Smad2/3 in liver tissues of mice compared to the model group (P<0.01). Amygdalin down-regulated the expressions of Col-I and α-SMA in JS-1 and LX-2 cells, and TGFβ R1, TGFβ R2 and p-Smad2/3 in LX-2 cells compared to the model group (P<0.05 or P<0.01). Moreover, 1 and 10 µmol/L amygdalin inhibited the mRNA and protein expressions of CD31 in LSECs and increased CD44 expression compared to the model group (P<0.05 or P<0.01).@*CONCLUSIONS@#Amygdalin can dramatically alleviate liver fibrosis induced by CCl4 in mice and inhibit TGF-β/Smad signaling pathway, consequently suppressing HSCs activation and LSECs dedifferentiation to improve angiogenesis.

In Vitro and In Vivo Evaluation of the Effectiveness and Safety of Amygdalin as a Cancer Therapy.

Cancer is one of the most important causes of death worldwide. Several studies have shown the efficacy of apricot kernel seed as a cancer therapy due to the presence of amygdalin. These studies have demonstrated amygdalin's cytotoxicity, antioxidant activity, and apoptosis in vitro using human cancer cell lines. However, no studies have demonstrated their cancer activity in vivo. The aim of this study is to develop an amygdalin-loaded niosomes (ALN) gel formulation as a drug delivery system in order to investigate the selectivity, efficacy, and toxicity of amygdalin as a cancer therapy in vivo using the 7,12-dimethylbenz (a) anthracene (DMBA) carcinoma rat model. Based on pre-formulation studies, the ALN formulation composed of Tween 60: cholesterol: dihexadecyl phosphate in a molar ratio of 1:2:0.1 was chosen as an optimum formulation because it has a percent of EE of 66.52% with a particle size of 269.3 nm and a reflux of 3.54 µg.cm-2.h-1. The ALN gel formulation was integrated into carbopol gel to be evaluated in vivo. Compared to DMBA control, treatment with ALN gel showed a reduction in the carcinoma volume and in the hyperplasia of the epidermis with no signs of edema. In conclusion, the ALN gel formulation could be an efficient cancer therapy.

Amygdalin as a chemoprotective agent in co-treatment with cisplatin.

Amygdalin is a naturally occurring glycoside used in traditional Chinese medicine and is known to have anti-cancer properties. Even though the anti-cancer properties of amygdalin are well known, its effect on normal cells has not been thoroughly investigated. The aim of the present study was to investigate a possible chemo-protective role of amygdalin against the cytotoxic effects of chemotherapy for normal human cells. Specifically, it was tested in combination with a strong chemotherapeutic drug cisplatin. Human non-tumorigenic MCF12F epithelial cell line, human fibroblasts cells, human breast cancer MCF7 and MDA-MB-231 cells were treated with cisplatin in a dose- and time-depended manner in the absence or presence of amygdalin. When MCF12F cells and fibroblasts underwent pre-treatment with amygdalin followed by cisplatin treatment (24 h amygdalin + 24 h cisplatin), the cell viability was increased (22%, p < 0.001) as indicated using MTT assay. As attested by flow cytometry, combination treatment was associated with decreased the percentage of late apoptotic cells compared with monotherapy (fold-change of decrease = 1.6 and 4.5 for 15 and 20 µΜ, respectively). Also, the proteins expression of PUMA, p53, phospho-p53 and Bax decreased, when a combination treatment was used vs. cisplatin alone, while the proapoptotic proteins Bcl-2 and Bcl-xL exhibited an increased tendency in the presence of amygdalin. Moreover, the levels of pro-apoptotic genes PUMA, p53, and BAX mRNA were significantly downregulated (∼83%, ∼66%, and ∼44%, respectively) vs. cisplatin alone, while the mRNA levels of anti-apoptotic genes BCl-2 and Bcl-XL were upregulated (∼44.5% and ∼51%, respectively), vs. cisplatin alone after 24 h of combination treatment. The study on the Combination index (CI) assay indicated that amygdalin could be possibly considered as an antagonist to cisplatin (2.2 and 2.3) for MCF12F and fibroblast cells, respectively. In contrast, for the breast cancer MCF7 and MDA-MB-231 cells, amygdalin and cisplatin indicated a synergistic effect (0.8 and 0.65), respectively. Our present findings suggest that amygdalin has chemo-modulatory effect when used in co-treatment with cisplatin and is able to protect normal breast cells as well as the fibroblasts during chemotherapy treatment, indicating a strong selective chemoprotective ability and may contribute to a better quality of life for cancer patients.

Apricot kernels' extract and amygdalin alter bleomycin-induced Ty1 retrotransposition, mitotic gene conversion in the trp-5 locus and reverse point mutations in ilv1-92 allele in Saccharomyces cerevisiae.

The present study aims to analyze the effect of apricot kernels' extract (AKE) and amygdalin (AMY) on bleomycin-induced genetic alternations. Five endpoints were analyzed: cell survival, Ty1 retrotransposition, mitotic gene conversion in the trp-5 locus, reverse point mutations in ilv1-92 allele, and mitotic crossing-over in the ade2 locus. The present work provides the first experimental evidence that bleomycin induces Ty1 retrotransposition in Saccharomyces cerevisiae. New data is obtained that the degree of DNA protection of AMY and AKE depends on the studied genetic event. AKE has been found to provide significant protection against bleomycin-induced Ty1 retrotransposition due to better-expressed antioxidant potential. On the other side, AMY better-expressed protection against bleomycin-induced mitotic gene conversion and reverse mutations may be attributed to the activation of the repair enzymes.

Anticancer Potential and Other Pharmacological Properties of Prunus armeniaca L.: An Updated Overview.

Prunus armeniaca L. (Rosaceae)-syn. Amygdalus armeniaca (L.) Dumort., Armeniaca armeniaca (L.) Huth, Armeniaca vulgaris Lam is commonly known as the apricot tree. The plant is thought to originate from the northern, north-western, and north-eastern provinces of China, although some data show that it may also come from Korea or Japan. The apricot fruit is used medicinally to treat a variety of ailments, including use as an antipyretic, antiseptic, anti-inflammatory, emetic, and ophthalmic remedy. The Chinese and Korean pharmacopeias describe the apricot seed as an herbal medicinal product. Various parts of the apricot plant are used worldwide for their anticancer properties, either as a primary remedy in traditional medicine or as a complementary or alternative medicine. The purpose of this review was to provide comprehensive and up-to-date information on ethnobotanical data, bioactive phytochemicals, anticancer potential, pharmacological applications, and toxicology of the genus Prunus armeniaca, thus providing new perspectives on future research directions. Included data were obtained from online databases such as PubMed/Medline, Google Scholar, Science direct, and Wiley Online Library. Multiple anticancer mechanisms have been identified in in vitro and in vivo studies, the most important mechanisms being apoptosis, antiproliferation, and cytotoxicity. The anticancer properties are probably mediated by the contained bioactive compounds, which can activate various anticancer mechanisms and signaling pathways such as tumor suppressor proteins that reduce the proliferation of tumor cells. Other pharmacological properties resulting from the analysis of experimental studies include neuroprotective, cardioprotective, antioxidant, immunostimulatory, antihyperlipidemic, antibacterial, and antifungal effects. In addition, data were provided on the toxicity of amygdalin, a compound found in apricot kernel seeds, which limits the long-term use of complementary/alternative products derived from P. armeniaca. This updated review showed that bioactive compounds derived from P. armeniaca are promising compounds for future research due to their important pharmacological properties, especially anticancer. A detailed analysis of the chemical structure of these compounds and their cytotoxicity should be carried out in future research. In addition, translational pharmacological studies are required for the correct determination of pharmacologically active doses in humans.

Amygdalin Induced Mitochondria-Mediated Apoptosis of Lung Cancer Cells via Regulating NF[Formula: see text]B-1/NF[Formula: see text]B Signaling Cascade in Vitro and in Vivo.

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide. Amygdalin, a natural compound commonly distributed in plants of the Rosaceae species, owns anticancer activity, less side effects, wide source, and relatively low price. Although the apoptosis is a central process activated by amygdalin in cancer cells, the underlying molecular mechanisms through which amygdalin induces the apoptosis of lung cancer cells remain poorly understood. In this research work, amygdalin could suppress the proliferation of lung cancer A549 and PC9 cells by CCK8 assay. Amygdalin significantly promoted the apoptosis of lung cancer A549 and PC9 cells stained with Annexin V-FITC/PI by flow cytometry assay. Furthermore, amygdalin dose-dependently decreased the mitochondrial membrane potential (MMP) with JC-1 dye by flow cytometry. To investigate the underlying molecular mechanisms through which amygdalin induced mitochondria-mediated apoptosis of cancer cells, the differentially-expressed genes with a fold change >2.0 and p < 0.05 were acquired from the cDNA microarray analysis. The results of qRT-PCR further confirmed that the differentially-expressed level of the NF[Formula: see text]B-1 gene was most obviously enhanced in lung cancer cells treated with amygdalin. The results of immunofluorescence staining, Western blotting and siRNA knockdown indicated that amygdalin induced mitochondria-mediated apoptosis of lung cancer cells via enhancing the expression of NF[Formula: see text]B-1 and inactivating NF[Formula: see text]B signaling cascade and further changing the expressions of proteins (Bax, Bcl-2, cytochrome C, caspase 9, caspase 3 and PARP) related to apoptosis, which were further checked by in vivo study of the lung cancer cell xenograft mice model accompanying with immunohistochemical staining and TUNEL staining. Our results indicated that amygdalin might be a potential activator of NF[Formula: see text]B-1, which sheds more light on the molecular mechanism of anticancer effects of amygdalin. These results highlighted amygdalin as a potential therapeutic anticancer agent, which warrants its development as a therapy for lung cancer.

Pharmacokinetics and anti-liver fibrosis characteristics of amygdalin: Key role of the deglycosylated metabolite prunasin.

BACKGROUND: Amygdalin (Amy) is a cyanoside and is one of the chief active ingredients in Persicae Semen, Armeniacae Semen Amarum, and Pruni Semen. Amy has extensive and remarkable pharmacological activities, including against anti-hepatic fibrosis. However, the pharmacokinetic and anti-liver fibrosis effects of Amy and its enzyme metabolite prunasin (Pru) in vivo have not been studied and compared, and studies on Pru are limited. PURPOSE: To investigate the pharmacokinetic characteristics and anti-liver fibrosis effect of Amy and its metabolite Pru in vivo and in vitro, and elucidate whether the metabolism of Amy in vivo for Pru is activated. METHODS: Pru was prepared from Amy via the enzymatic hydrolysis of ß-glucosidase, and isolated by silica gel column chromatography. An efficient and sensitive ultrahigh-performance liquid chromatography-Q exactive hybrid quadrupole orbitrap high-resolution accurate mass spectrometry was developed and validated to determine simultaneously Amy and Pru in rat plasma after dosing intravenously and orally for pharmacokinetic studies. The affinities of Amy and Pru for ß-glucosidase were compared by enzyme kinetic experiments to explain the possible reasons for the differences in pharmacokinetic behavior. In vitro, the inhibitory effects of Amy and Pru on hepatic stellate cell activation and macrophage inflammation on JS1 and RAW 264.7 cells were determined. In vivo, the ameliorative effects of Amy and Pru on liver fibrosis effects were comprehensively evaluated by CCl4-induced liver fibrosis model in mice. RESULTS: The standard curves of Amy and Pru in rat plasma showed good linearity within the concentration range of 1.31-5000.00 ng/ml, with acceptable selectivity, carry-over, detection limit and quantification limits, intra- and inter-day precision, accuracy, matrix effect, and stability. The Cmax and AUC(0-∞) of Pru (Cmax = 1835.12 ± 268.09 ng/ml, AUC(0-∞) = 103,913.17 ± 14,202.48 ng•min/ml) were nearly 79.51- and 66.22-fold higher than those of Amy (Cmax = 23.08 ± 5.08 ng/ml, AUC(0-∞) = 1569.22 ± 650.62 ng•min/ml) after the oral administration of Amy. The oral bioavailability of Pru (64.91%) was higher than that of Amy (0.19%). The results of enzyme hydrolysis kinetics assay showed that the Vmax and Km of Pru were lower than those of Amy in commercial ß-glucosidase and intestinal bacteria. In vitro cellular assays showed that Amy and Pru were comparable in inhibiting the NO production in the RAW264.7 cell supernatant and the mRNA expression of α-SMA and Col1A1 in JS1 cells. Amy and Pru were also showed comparable activity in ameliorating CCl4-induced liver fibrosis in mice. CONCLUSION: The pharmacokinetic characteristics of Amy and Pru in rat plasma were significantly different. After the separate gavage of Amy and Pru, Amy was absorbed predominantly as it's metabolite Pru, whereas Pru was absorbed predominantly as a prototype. The anti-liver fibrosis effects of Amy and its deglycosylated metabolite Pru were comparable in vivo and in vitro. The deglycosylated activated metabolite Pru of Amy plays an important role in anti-liver fibrosis. These findings will facilitate the further exploitation of Amy and Pru.

Xuanfei Baidu Decoction reduces acute lung injury by regulating infiltration of neutrophils and macrophages via PD-1/IL17A pathway.

The pathogenic hyper-inflammatory response has been revealed as the major cause of the severity and death of the Corona Virus Disease 2019 (COVID-19). Xuanfei Baidu Decoction (XFBD) as one of the "three medicines and three prescriptions" for the clinically effective treatment of COVID-19 in China, shows unique advantages in the control of symptomatic transition from moderate to severe disease states. However, the roles of XFBD to against hyper-inflammatory response and its mechanism remain unclear. Here, we established acute lung injury (ALI) model induced by lipopolysaccharide (LPS), presenting a hyperinflammatory process to explore the pharmacodynamic effect and molecular mechanism of XFBD on ALI. The in vitro experiments demonstrated that XFBD inhibited the secretion of IL-6 and TNF-α and iNOS activity in LPS-stimulated RAW264.7 macrophages. In vivo, we confirmed that XFBD improved pulmonary injury via down-regulating the expression of proinflammatory cytokines such as IL-6, TNF-α and IL1-ß as well as macrophages and neutrophils infiltration in LPS-induced ALI mice. Mechanically, we revealed that XFBD treated LPS-induced acute lung injury through PD-1/IL17A pathway which regulates the infiltration of neutrophils and macrophages. Additionally, one major compound from XFBD, i.e. glycyrrhizic acid, shows a high binding affinity with IL17A. In conclusion, we demonstrated the therapeutic effects of XFBD, which provides the immune foundations of XFBD and fatherly support its clinical applications.

Life-Threatening Cyanide Intoxication after Ingestion of Amygdalin in Prehospital Care.

Amygdalin is originally a natural cyanogenic glycoside available as a dietary supplement used in the alternative treatment of cancer patients. Amygdalin hydroxylates to toxic cyanide in the body, which can cause life-threatening intoxication. The case report presents a 72-year-old patient with life-threatening cyanide poisoning after ingesting a dietary supplement containing amygdalin identified in prehospital care, which was successfully treated with hydroxocobalamin.

Interactions Between Ephedra sinica and Prunus armeniaca: From Stereoselectivity to Deamination as a Metabolic Detoxification Mechanism of Amygdalin.

Mahuang-Xingren (MX, Ephedra sinica Stapf-Prunus armeniaca L.) is a classic herb pair used in traditional Chinese medicine. This combined preparation reduces the toxicity of Xingren through the stereoselective metabolism of its main active ingredient amygdalin. However, whether stereoselectivity is important in the pharmacokinetic properties of amygdalin either in the traditional decoction or in the dispensing granules is unclear. Amygdalin is hydrolyzed to its metabolite, prunasin, which produces hydrogen cyanide by degradation of the cyano group. A comprehensive study of the metabolic pathway of amygdalin is essential to better understand the detoxification process. In this article, the potential detoxification pathway of MX is further discussed with regard to herb interactions. In this study, the pharmacokinetic parameters and metabolism of amygdalin and prunasin were investigated by comparing the traditional decoction and the dispensing granule preparations. In addition, several potential metabolites were characterized in an incubation system with rat liver microsomes or gut microbial enzymes. The combination of Xingren with Mahuang reduces exposure to D-amygdalin in vivo and contributes to its detoxification, a process that can be further facilitated in the traditional decoction. From the in vitro co-incubation model, 15 metabolites were identified and classified into cyanogenesis and non-cyanogenesis metabolic pathways, and of these, 10 metabolites were described for the first time. The level of detoxified metabolites in the MX traditional decoction was higher than that in the dispensing granules. The metabolism of amygdalin by the gut microbial enzymes occurred more rapidly than that by the rat liver microsomes. These results indicated that combined boiling both herbs during the preparation of the traditional decoction may induce several chemical changes that will influence drug metabolism in vivo. The gut microbiota may play a critical role in amygdalin metabolism. In conclusion, detoxification of MX may result 1) during the preparation of the decoction, in the boiling phase, and 2) from the metabolic pathways activated in vivo. Stereoselective pharmacokinetics and deamination metabolism have been proposed as the detoxification pathway underlying the compatibility of MX. Metabolic detoxification of amygdalin was quite different between the two combinations, which indicates that the MX decoctions should not be completely replaced by their dispensing granules.