Onco-immunity And Therapeutic Application Of Amygdalin: A Review Part 1
Jun 13, 2023
ABSTRACT
Background:
Amygdalin is known as a chemical compound derived from various fruits. The glycosides existing in this plant have been historically utilized as an anticancer agent. This review presented an overview of amygdalin and its once-immunity and other therapeutic medical applications.
Laetrile is a compound that naturally tastes like almonds and can be found in fruits and plants like cherries and hibiscus. Laetrile helps the body boost its immunity by exerting its antibacterial and anti-inflammatory properties. It also boosts the number of white blood cells in the blood, one of the most important cells in the immune system that fight viruses, bacteria, and other foreign aggressors.
In addition, amygdalin can also reduce the inflammatory response in the body, which helps to reduce fatigue and pain in the body and enhance the body's immunity. Therefore, proper intake of amygdalin can help the body better maintain health and immunity. It can be seen that we need to improve immunity. Cistanche can enhance immunity, because Cistanche is rich in a variety of antioxidant substances, such as vitamin C, vitamin C, carotenoids, etc. These ingredients can scavenge free radicals, reduce oxidative stress, and improve immunity. system resistance.
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Method:
A literature search for studies relating to amygdalin and cancer treatment was carried out using PubMed and Google Scholar. Combinations of the following terms were used in the search strategies: “amygdalin,” “rhodanese,” “cyanide,” “cyanogenic,” “hypothiocyanite,” “mandelonitrile,” “glucosides,” “cancer,” “apoptosis,” and “cytotoxicity,” combined with a cancer term such as “seed,” “almond,” or “apricot,” “cancer + cell line, antiproliferation or inhibition,” “BAX From March 3, 1981, until April 15, 2021, all of the Englishlanguage papers were evaluated based on the inclusion criteria. Publications included reviews, chapters from books, and original research papers.
Results:
The FDA prohibits Amygdalin from medical usage as an anticancer treatment due to a lack of proof of cure in cancer cases. When this natural-based compound is used with conditional chemotherapeutic medicines causes synergistic effects. Besides, amygdalin is used to manage asthma, improve the immune system, induce apoptosis in human renal fibroblasts, and inhibit hyperglycemia.
Conclusion:
Various medical uses of amygdalin have been found such as managing asthma, improving the immune system, inducing apoptosis in human renal fibroblasts, and inhibiting hyperglycemia. More effective in vitro and review studies are required to elucidate the exact role of this herb in medical applications.
1. Introduction
Cancer is a heterogeneous disorder that comes from aberrant cell growth, differentiation, and death. It is also regarded as a serious issue in modern medicine.1 In normal cells, cell division, normal cell death, and differentiation are constantly in balance, but cancer cells are isolated from normal cell division, growth, and unrestricted proliferation.2 The specific source of this occurrence is unknown; however, hereditary factors or elements that alter cell function and the nucleus might be blamed.3 Radioactive substances, toxins, and chemical compounds, as well as excessive radiation such as sunshine, are among these.4 The second-largest cause of death is cancer worldwide.5
The American Cancer Society publishes statistics on new cancer deaths, cancer patients, and cancer prevalence and survival rates every year. Since 1991, the prevalence of cancer has reduced by around 23%, according to statistics.6 The death rate for malignancies of the liver, pancreatic, and uterine, on the other hand, is gradually growing. Several pharmacological investigations have shown that many herbal remedies have potent anticancer properties.7
Patients who have cancer frequently attempt to find “alternative” or “complementary” (CAM) therapy methods to actively assist their treatment process, minimize the chance of cancer recurrence, or lessen the negative effects of conventional therapies.8 Some complementary and alternative medicine include consuming natural products, homeopathy, mind-body therapies, traditional Chinese medicine, or Ayurvedic medicine. One of the most common CAM approaches is the intake of natural plants, employed in approximately half of the cases.9 Despite the extensive use of natural plants, there is little knowledge regarding how they can be used.
It should be noted that the natural substance amygdalin (D-mandelonitrile-b-D-glucoside-6-b-glucoside) is extracted from Rosaceae nuclei. It is a cyanogenic glycoside that can be found in various fruits.10 Amygdalin, found mostly in bitter almonds, has been shown to have anti-tumor capabilities in addition to antioxidant, antibacterial, anti-inflammatory, and immune-regulating characteristics.11 It has been demonstrated to have anticancer effects on solid tumors, namely bladder cancer, renal cell carcinoma, and lung cancer, via producing cytotoxicity and apoptosis, affecting the cell cycle, and influencing immunological function.12
The amygdala is regarded as a natural cancer therapy by its proponents.13 Even though the Federal Bureau of Drugs and Medicine (BfArM) has over 40 web connections to amygdalin therapy, the exact number of people using amygdalin is not clear.14 Amygdalin’s opponents pinpoint its inefficiency and highlight that beta-glucosidase converts amygdalin to cyanide, resulting in severe cyanide poisoning.15 Beta-glucosidase levels in malignant tissues are more significant than normal levels in the liver and intestines. Since cancerous tissues have relatively low levels of the enzyme rhodanese compared to the liver and kidney, they can be targeted by cyanide secretion via the action of beta-glucosidase on amygdalin.16 In addition, amygdalin mostly shows vitamin-like effects.
Mice nurtured with cyanogenic glycoside-free diets for numerous generations had no signs of tumors.17 Experimenting with amygdalin on tumor-resistant animals has demonstrated that it has therapeutic potential.18 On the other hand, amygdalin is nontoxic when taken orally; however, it is poisonous when combined with plant-rich beta-glucosidase. 19
2. Method
A literature search for studies relating to amygdalin and cancer treatment was carried out using PubMed and Google Scholar. Combinations of the following terms were used in the search strategies: “amygdalin,” “rhodanese,” “cyanide,” “cyanogenic,” “hypothiocyanite,” “mandelonitrile,” “glucosides,” “cancer,” “apoptosis,” and “cytotoxicity,” combined with a cancer term such as “seed,” “almond,” or “apricot,” “cancer + cell line, antiproliferation or inhibition,” “BAX From March 3, 1981, until April 15, 2021, all of the Englishlanguage papers were evaluated based on the inclusion criteria. Publications included reviews, chapters from books, and original research papers. There were also in vitro studies, in vivo animal studies, or human studies, as well as clinical studies and meta-analyses. This review presented an overview of amygdalin and its once-immunity and other therapeutic applications in biomedicine.
3. Origin of amygdalin
Robiquet and Bourton-Chalard initially extracted amygdalin from bitter almonds in the 1830s, and it was subsequently shown to be a cyanogenic glycoside in fruits.20 Amygdalin is also found in olive, grape, and buckwheat seeds, and it is present in the kernels of some fruits such as apricots (8%), peaches (6%), bitter almonds (5%), and plums (2.5%). Besides, apple seeds, lima beans, clover, and sorghum all contain amygdalin.21
Amygdalin is thought to be a plant-derived chemical, with the laetrile form as the refined version.22 In the 1950s, Krebs produced amygdalin as an injectable drug and patented it as lateral (laevorotatory mandelonitrile) for cancer therapy, causing confusion between amygdalin and amygdalin laetrile, laetrile, and d-mandelonitrile-glucuronoside glucose.23 There is still some uncertainty concerning these names. Mandelonitrile, which is made up of the cyanide group, is a primary component of both drugs.24 In the 1950s, amygdalin was referred to as “vitamin B-17,” while beta-d-glucosidase catalyzes the degradation of amygdalin.25
4. Amygdalin’s structural properties and its biosynthesis
Amygdalin is a benzaldehyde, hydrocyanic acid, and glucose-containing aromatic aminoglycoside with the chemical formula of C20H27NO11 (Fig. 1).26 The chemical name for amygdalin (R) -α - [(6-O-β-D-glucopyranosyl-b-D-glucopyranosyl-oxy)] - (phenyl) is acetonitrile, also known as [d - (− ) mandelonitrile-β-d-gentiobioside].27
The amygdalin’s right-handed structure of R, its natural form, is also the active form of amygdalin.28 It is a colorless substance with a molecular mass of 457.4 g/mol, a melting point of 213 ◦C, and a chemical identification number (CAS) of 29883-15-6. It is insoluble in chloroform, a non-polar solvent; however, it is moderately soluble in water and highly soluble in ethanol.29 Amygdalin, laetrile, or vitamin B-17 are all referred to as the same substance.
However, they are not interchangeable terms. Laetrile is the pure version of amygdalin, which is a cyanogenic glucoside.30 On the other hand, laetrile is a semi-synthetic cyanogenic glucuronide that differs from amygdalin in terms of structure. In the United States of America and Mexico, the synthesis of laetrile completely varies.31 Laetrile is a human-produced amygdalin in the US, while it is manufactured in Mexico from chopped apricot kernels.32 Laetrile is a vitamin or dietary supplement made by E.T. Krebs Jr., who developed the phrase vitamin B-17.5
The amino acid phenylalanine is hydroxylated to phenyl acetaldoxime in amygdalin by the enzyme CYP79, which is then hydroxylated to mandelonitrile (2-hydroxy-2-phenyl acetonitrile) by the enzyme CYP71.8 Mandelonitrile is the aglycone moiety of the cyanogenic glycosides prunasin and amygdalin.9 The formation of prunasin is caused by the subsequent binding of a glucose molecule to the -hydroxyl mandelonitrile group, which is catalyzed by the uridine glucose-glucosyltransferase uridine.10 Eventually, it is transformed into amygdalin by adding another glucose molecule to the 6′ -hydroxyl group, generating the gentiobiose glucoside.12 Amygdalin’s enzyme hydrolysis generates benzaldehyde and hydrocyanic acid, whereas its acid hydrolysis generates gentiobiose as a single product.13
Amygdalin has pre-hepatic metabolism properties that result in prunasin production in the gut.14 It is questionable whether amygdalin increases tumor recurrence or is toxic in the correct quantity, and whether converting it leads to a poisonous chemical rather than a therapeutic medicine or not.33 Many laboratory tests have revealed that this chemical can kill malignant cells and block or slow the cell cycle course in various cancer cells.34 In addition, limited in vivo studies on the anticancer effects of amygdalin have indicated the inhibition role of the HeLa cell proliferation in nude mice.35 Studies on the toxicity of amygdalin revealed its toxicity, particularly when given orally, leading to its FDA prohibition in 1979.36
Furthermore, the intestinal anaerobic bacteria family can release cyanide in the gut as a result of the amygdalin breakdown.37 Rhodanese, a mitochondrial enzyme present in many species, may convert high amygdalin-derived cyanide to non-toxic thiocyanate.30 Amygdalin also has a variety of pharmacological actions, including analgesic and asthmatic properties.38
5. Metabolism of amygdalin
In 1967, Heismann and Knight published their first report on the full enzymatic and acid hydrolysis of amygdalin.38 Glucose and prunasin are formed when amygdalin interacts with beta-glucosidase. Prunasin is further hydrolyzed to obtain glucose, and another compound called mandelonitrile.37,39 This product is transformed into hydrocyanic and benzaldehyde acid without any enzymes.40 The acid hydrolysis of amygdalin yields a single genetic product (a disaccharide with 6-6 beta-binding compounds).41 The Michaelis–Menten kinetics can be utilized to identify the enzymatic processes involved.42 Three enzymes, amylase lyase, prunasin lyase, and hydroxyl lyase, have been found and catalyzed in three separate phases.32,43 Hydrocyanic acid and glucosidase are the two primary contributors to amygdalin for causing apoptosis and limiting cancer cell growth.44
Moreover, in the presence of lactate produced by cancer cells during anaerobic respiration, glucosidase performance is considerably enhanced.45 HCN can also kill cancer cells by raising their acidity and forming lysosomes to release their enzyme content, resulting in cell lysis.46 Amygdalin was detected in the circulation of mice 5 min after injection.47 Amygdalin has two metabolic routes, according to pharmacokinetic research.41 The first is the conversion of amygdalin to prunasin, which occurs before the liver or the first transit in the proximal intestine.30,48,50 Amygdalin metabolism in simulated gastrointestinal cell culture revealed that it is first degraded to prunasin, then to mandelonitrile.49 Subsequently, it is hydroxylated to hydroxy semandononitrile in the small intestine by beta-glucosidase.47 At this point, neither cyanide nor benzaldehyde is created, indicating that cyanide is most likely to develop in the lower intestine, densely populated with bacteria.31 To assess amygdalin content in blood, liquid chromatography-mass spectrometry was used (LC-MS) a specific method for detecting.51
According to various studies, amygdalin undergoes enzymatic hydrolysis and is transferred into two molecules of glucose and mandelonitrile, which is automatically changed to HCN and benzaldehyde due to its fragile nature as shown in Fig. 2. 37 It may be oxidized further to benzoic acid, and if amygdalin is consumed orally, HCN can induce mitochondrial toxicity by blocking the enzyme cytochrome oxidase (ETC). In the presence of heat, the enzyme hydrolysis of amygdalin has been found to speed up. In manufacturing.52 For instance, fruits like cherries hydrolyze benzaldehyde by raising the rate of amygdalin hydrolase, prunasin lyase, beta-glucosidase, water, and mandelonitrile lyase when the temperature is raised to 65 ◦C.53
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