Amygdalin: A Review on Its Characteristics, Antioxidant Potential, Gastrointestinal Microbiota Intervention, Anticancer Therapeutic and Mechanisms, Toxicity, and Encapsulation

Abstract

Bioactive amygdalin, found in high concentrations in bitter almonds, has been recognized as a symbol of the cyanogenic glycoside chemical organic substance, which was initially developed as a pharmaceutical for treating cancer after being hydrolyzed to hydrogen cyanide (HCN). Regrettably, research has shown that HCN can also damage normal cells, rendering it non-toxic to the human body. Extreme controversy surrounds both in vivo and in vitro studies, making its use risky. This review provides an extensive update on characteristics, antioxidant potential, gastrointestinal microbiota intervention, anticancer therapeutic, mechanisms, toxicity, and encapsulation of amygdalin. Antioxidant, anti-tumor, anti-fibrotic, antiatherosclerosis, anti-inflammatory, immunomodulatory, and analgesic characteristics, and the ability to improve digestive and reproductive systems, neurodegeneration, and cardiac hypertrophy are just some of the benefits of amygdalin. Studies verified the HCN-produced amygdalin to be harmful orally, but only at very high doses. Although intravenous treatment was less effective than the oral method, the oral route has a dose range of 0.6 to 1 g daily. Amygdalin's toxicity depends heavily on the variety of bacteria in the digestive tract. Unfortunately, there is currently no foolproof method for determining the microbial consortium and providing a safe oral dosage for every patient. Amygdalin encapsulation in alginate-chitosan nanoparticles (ACNPs) is a relatively new area of research. Amygdalin has an enhanced cytotoxic effect on malignant cells, and ACNPs can be employed as an active drug-delivery system to release this compound in a regulated, sustained manner without causing any harm to healthy cells or tissues. In conclusion, a large area of research for a substance that might be the next step in cancer therapy is opened up due to unverified and conflicting data.

Keywords: amygdalin; anticancer; antioxidant; encapsulation; mechanisms; microbiota intervention; toxicity.

Figure 1

Amygdalin (A) and laetrile (B) chemical structures.

Figure 2

Controlling AMD in cancer and normal cells: the function of RHD and BGD [27].

Figure 3

Amygdalin’s anti-tumor effects on cell proliferation.

Figure 4

Amygdalin’s impact on Akt-mTOR signaling and β1 and β4 integrin expression. Lung cancer cell adhesion, migration, and proliferation are slowed when ILK and FAK expression is suppressed. The growth and proliferation of cancer cells are regulated by a phosphorylation cascade that includes the mTOR/Rictor complex, which amygdalin can block.

Figure 5

A schematic depicting how amygdalin induces apoptosis; amygdalin activates Pp38, which increases the level of BAX apoptotic proteins and decreases the quantity of Bcl-2 anti-apoptotic proteins and activates caspase-3.

Figure 6

An illustration showing how anionic and cationic ACNPs loaded with amygdalin are made.

Figure 7

Schematic diagram of preparation process of MNP-β-Glu-PEG.