The Therapeutic Potential of Apricot Seeds (Armeniacae Semen) as Antiinflammatory, Antiasthmatic, and Immunomodulatory Natural Remedy
Relief for Ulcerative Colitis and Asthma
Apricot seeds (Armeniacae Semen) have long been used in traditional medicine throughout the world, and have a particularly rich history of use in Traditional Chinese Medicine (TCM). Their principal active ingredient, a cyanogenic glycoside, amygdalin, has even been the source of controversy as the notorious anti-cancer drug Laetrile investigated in the 1970s. Here we will look at the studies and try to separate fact from fiction and will examine its properties from a modern research, historical and traditional Chinese perspective in how it has been used and continues to be used effectively within the scope of TCM practice.
Xing Ren (Semen Armeniacae) Apricot Kernel
Channels: Lung / LI, Properties: Bitter, Slightly Warm, Slightly Toxic
“Descends Lung Qi, Disperses Wind-Cold, Stop Cough, Clear Phlegm, Calm Wheezing, Moisten Intestines, Unblock bowels.” Anti-asthmatic, Anti-bacterial, Anti-Diabetic, Anti-mutagenic, Anti-neoplastic, Antitussive (Chen and Chen)
****This herb does have mild toxicity because of its active constituent amygdalin, and so is best used in small doses (5 kernels or less/day) prophylactically for minor asthmatic or intestinal symptoms. To unlock the full therapeutic potential this herb should be used in as part of an herbal formulation under the guidance of an integrative physician or Chinese medicine practitioner as part of an overall protocol.
Armeniacae semen is host to a variety of constituents, potentially with mutually enhancing therapeutic properties; as summarized by Minaiyan et al, 2014:
“Apricot kernel is a good dietary source of protein, oil, fibre, phenolic and cyanogenic compounds [chiefly amygdalin]. Oleic acid and linoleic acid are the main components of the oil fraction and pectin polysaccharides, cellulose and hemicellulose are the main polysaccharides.” [14]
ANTI-INFLAMMATORY AND ANTI-ASTHMATIC
Regarding its use in pulmonary and inflammatory disorders, the current in vitro, and in vivo studies provide evidence for semen armeniacae and its active constituent amygdalin to be potentially effective antitussive [13], anti-inflammatory agents, blocking both the COX-2 pathway in prostaglandin synthesis and the iNOS pathway to reduce NO levels in inflamed tissues [19, 12, 10]. As well it has shown efficacy as an analgesic that inhibits TNF-a and IL-1b expression [10,25], antispasmodic [11] and bronchodilating via inhibition of Histamine H1 receptors [12] and as an agonist for B-2 adrenergic receptors. Other studies point to Armeniacae’s ability to directly modulate the central cough center in the medulla oblongata via its cyanogenic components. [13] Thus, in vitro evidence as well as in vivo evidence (in herbal formulas and as a lone herb) suggest that it may serve as a powerful antiinflammatory, antiasthmatic agent.
Other studies have shown that in vitro semen armeniacae can lower expression by 50% of inflammatory cytokines such as IL-4, IL-5, and IL-6. [18] Regarding transcriptional control of inflammation, another study found, in a mouse model of acute lung injury, amygdalin inhibited activation of the inflammatory transcription factor, NF-kB, and the NLRP3 inflammasome protein, two key intracellular inflammatory mediators. [23] Another study finds it may be effective anti-inflammatory agent in the skin as well, by modulating cytokine expression in keratinocytes. [22]
Some studies have shown that ephedrae herba and semen armeniacae have synergistic effects, and this is highlighted by a study showing their effective use clinically in Ma Xing Shi Gan Tang (MXGST) in China. [13] A study looking at the combination of Ephedrae Herba and Semen Armeniacae in a mouse model of asthma, found that the two herbs inhibited the apoptosis of airway epithelial cells, and additionally, under electron microscopy, that the herbal combination was effective compared to controls to repair the fine ultrastructure of the epithelial cells. [17] This study also found that the two herbs prevented the overexpression of EGFR (Epidermal Growth Factor Receptor) and Bcl-2, both of which promote cell division and can be overexpressed in many cancers. This indicates that herbal combination may have efficacy in preventing inflammation-dependent dysplasia in lung tissue.
IMMUNOMODULATION
As referenced above, various studies suggest that semen armeniacae may prevent histamine induced bronchoconstriction by inhibition of H1 receptors, while also actively stimulating bronchodilation and smooth muscle relaxation via B2 receptors. However, other studies suggest a direct immunomodulatory function as well. In a mouse model of allergic asthma, oral treatment with semen armeniacae inhibited several measures of airway hyperreactivity, including air flow resistance and leukocyte recruitment, especially of eosinophils. [16] Moreover, in this study they found that Semen Armeniacae treated mice had decrease IL-4 expression (a Th2 type / Eosinophilic cytokine) while there was no effect on IFN-y (a Th1 type antiviral cytokine). As allergic asthmatic conditions are generally seen as an overactive Th2 type response, these results were highly significant and led the researchers to suggest that semen armeniacae could be a helpful therapy to reduce hyperactive Th2 responses in allergic conditions like asthma. [16]
T Helper cells are often considered directors of the immune system because of their ability to coordinate immune responses through prolific cytokine production. They can be split into two phenotypes based on the class of cytokines they produce, Th1 or Th2. Th1 cells help protect the body from intracellular pathogens (viruses /cancer) whereas Th2 cells help protect the body from extracellular pathogens, (bacteria / allergens) and ideally these responses should be in a healthy balance.
Another study with a mouse model of atherosclerosis, showed armeniacae semen’s immunomodulatory potential and found that “amygdalin could suppress inflammatory responses and promote the immunomodulation function of Tregs.” [4] The vasculature of the amygdalin treated rats (in injection form) ultimately had “enlarged lumen area and the loss of atherosclerotic plaque… and a 2-fold decrease in triglyceride (TG), 1.5-fold decrease in total cholesterol (TC) and low density lipoprotein (LDL).” [4] It is interesting to note here that the other traditional chinese herb with high amygdalin content, tao ren (semen persicae), is commonly used for blood flow related disorders, termed "blood stasis" in traditional chinese medicine.
Another study found that amygdalin promotes fracture and wound healing through TGF-B signaling. [9] This further indicates a potential role as a bidirectional modulator of inflammation responses.
ULCERATIVE COLITIS (UC)
A 2014 mouse model of ulcerative colitis found that both oral and intraperitoneal injected semen armeniacae extracts were effective in improving several histopathological indicators of disease in IBD.
The study concluded that the tannins in the apricot kernels assisted to “repair intestinal mucosal layers” [14] Tannins are a class of high weight, astringent polyphenolic biomolecules that are large enough to interact with other macromolecules such as proteins. [28] Pectin content in armeniacae is also deemed important in promoting the healing process. Pectin, a soluble fiber, studies have shown, is fermented by the microbiota of our gut to form the important regenerative and antiinflammatory short chain fatty acids (SCFAs) which provide the fuel for cells in the colon mucosal layers. [14] Moreover, apricot kernel extract may also directly “stabilize the cell membrane and prevent the oxidation of membrane lipids” due to its high content of small free radical scavenging molecules. [14]
COVID-19
Due to thousands of years of traditional usage, and the recent efficacy semen armeniacae has shown as a respiratory anti-inflammatory agent, there has been interest in its use for COVID-19 related pathology. A recent 2021 study by Wang, et al, investigated semen armeniacae’s potential therapeutic value to assist in treatment of COVID-19 and concluded that “amygdalin is a candidate compound for COVID-19 treatment by regulating IL6, SRC, MAPK1 EGFR. Meanwhile, amygdalin has a strong affinity for SARS-CoV-2 3CLpro and SARS-CoV-2 ACE2 and therefore prevents the virus transcription and dissemination.” [26] Another recent study analyzed the potential for the asthma formula we discussed above to treat COVID-19: Ma Xing Shi Gan Tang (MXSGT) with the four synergistic herbs (armeniacae semen, ephedrae herba, gypsum fibrosum, and glycyrrhizae rhizome). [27] They found this herbal combination to also hold promise and to deserve further clinical studies.
The most promising herbal formulations which have been studied for COVID-19 include Qing Fei Pai Du Tang, which features semen armeniacae (and the rest of MXSGT) prominently in its 21 ingredient blend based on traditional formulations. This formula is undergoing a clinical trial in the US as well at UCLA estimated completion in 2022.
Another herbal formula containing MXSGT and armeniacae semen, Lian Hua Qing Wen has been heavily investigated in China for COVID-19 and has proved efficacious in several small meta-analyses of several randomized controlled trials.
Other COVID-19 studies of formulas including armeniacae semen:
Figure 2. Amygdalin: a phenyl aromatic ring, attached to a cyanide group and two glucose molecules.
CANCER
There is accumulating in vitro and in vivo evidence that amygdalin, the active constituent in both tao ren (semen persicae), and xing ren (semen armeniacae), has significant anticancer properties in a variety of cancer cell lines, specifically to induce the intrinsic apoptosis pathway and arrest cell cycle in various stages. Studies have documented these effects in bladder, prostate, cervical, colon, hepatic, pancreatic, breast and leukemia cancers in vitro. [1,2,3,5,6,7,8,31,32,33] Several of these studies note how amygdalin affects different cancer cell lines differently, for example it arrests cell cycle in some lines and induces apoptosis in others. However, all effects seem to inhibit growth and prevent invasion and metastasis. Of particular relevance, in 2013, Chen et al, demonstrated that amygdalin was selectively toxic to cervical cancer cells while not being toxic to benign embryonic cells. [3] Moreover, they were able to show significant induction of apoptosis in a live in vivo mouse model of the same cancer. [3] Saleem, et. al. 2018 found that amygdalin induces anticancer effects through promoting apoptosis and inhibiting angiogenesis. The induction of apoptosis was mediated in various studies by increased Bax and caspase production (pro-apoptotic) and decreased Bcl-2 (anti-apoptotic), as well as by arresting the cell cycle in the G0/G1 phase. [1,2,3,5,6,7,8,29]
However, the toxicology in humans needs to be carefully evaluated here, as amygdalin can have a cyanogenic ("cyanide-producing") property when it is hydrolyzed. Animal and human studies verify however, that it is less toxic when used intravenously than when taken orally. [29] Some have hypothesized, this is due to the metabolism of amygdalin. As a cyanogenic glycoside, it is metabolized by B-glucosidases which are present in the intestines. [29] This would cause a local release of benzaldehyde and hydrocyanic acid (HCN). Cyanide (CN-) works its toxicity via inhibition of mitochondrial Complex IV cytochrome c oxidase, which effectively shuts down cellular respiration. Outside of the intestines, glucosidases are expressed at relatively low levels, with the exception of cancer cells which can express from 100%-3600% more B-glucosidase activity than nearby healthy tissues. [29] This is due to the well known glucose affinity that cancer cells have due to their use of fermentation as an additional source of energy. Moreover, cancer cells tend to be deficient in the rhodanese enzyme needed to detoxify HCN. [3,29] This distinction in enzyme activity would lead to a local release of HCN and benzaldehyde (both with documented anticancer properties) local to the cancer microenvironment. Nevertheless, others argue that in light of the pleiotropic effects of amygdalin, assumptions as to the mechanisms of its anticancer effects are premature, and further studies are strongly needed to investigate the biological mechanisms, in particular to discover how it modulates apoptosis and cell cycle protein gene expression. Other mechanisms such as its immunomodulatory actions may play a role in its anticancer mechanisms.
The original controversial research done on amygdalin by Dr. Sugiura at Sloan Kettering in the 1970s was discredited by small clinical trials with ambiguous dosage transparency and a lack of controls by Moertel, et al. However, Dr. Sugiura maintained that amygdalin did show promise, in particular to significantly reduce the likelihood of metastasis in lung cancer mouse models. [24] Further clinical trials are needed with new approaches and modern laboratory technology to fully understand the potential role of amygdalin and amygdalin containing medicinals as an adjunctive cancer therapy. Oral use of semen persicae (peach seed) and semen armeniacae (apricot seed) needs to be carefully approached, due to the cyanogenic property of amygdalin in the intestines. This caution is seen in its usage in Traditional Chinese Medicine, where low dose usage, now studied in animal and clinical settings, are proving to be safe and efficacious for inflammatory intestinal and pulmonary conditions. As well, actions are taken to reduce the amygdalin content of the kernels prior to administration in traditional clinical usage.
TRADITIONAL USAGE
We will end with an analysis of its traditional usage based on Bensky’s Chinese Herbal Medicine: Materia Medica, 3rd edition. [30]
Classified as a bitter, warm and draining herb, xing ren (semen armeniacae) is used traditionally for a wide variety of coughs (both hot or cold), but because of its moistening ability due to its high oil content, it is particularly effective for external dry coughs. Semen armeniacae can descend "rebellious qi" while also dispersing wind-cold and phlegm-damp pathogens from the lungs. Zhang Bing-Cheng describes that it exercises its dispersing quality indirectly by descending and regulating the lung qi; it restores the smooth flow of the qi mechanism and allows the body to effectively release the exterior to dispel the pathogen.
Li Shi-Zhen adds that it can release the muscle layer as it descends qi and reduces accumulations, and can kill parasites and heal sores owing to its toxicity. Xing ren is cautioned for patients with a yin deficiency or severe qi deficiency, and is not advised for patients with diarrhea due to its moistening properties on the intestines, or for children due to its slight toxicity. Traditionally, 10-20 seeds is considered toxic in children and 40-60 seeds is toxic for adults. The powdered seeds will be 4-5 times more toxic than a cooked decoction. When taken as a cooked decoction in normal dosage ranges, no toxicity or side effects are generally expected. Cyanogenic glycosides like amygdalin are generally unstable, and boiling them as in a decoction will reduce toxicity by half or more.
Interestingly, semen armeniacae is often paired with tao ren (semen persicae), which also possesses significant amygdalin content. While semen persicae works to invigorate the blood via the heart and liver channels, semen armeniacae can move the qi, open and restore the movement and function of lungs and large intestine. However semen persicae is also recognized to have an ability to calm wheezing and benefit the lungs in traditional usage, which is interesting given that both herbs possess high levels of the same compound.
CONCLUSION
To conclude, we can see that xing ren (semen armeniacae), the apricot kernel, via its active constituent amygdalin, as well as its other phenolic and fibrous components, have positive effects to modulate inflammation and immune activity, can be a beneficial adjunctive therapy in asthmatic and other pulmonary and intestinal inflammatory conditions, and holds promise as a potential adjunctive therapy for cancer care. We have seen in this review how the modern scientific research bears out many of the previously held traditional wisdom as to semen armeniacae’s therapeutic usage, such as its use in lung and intestinal conditions. Apricot and Peach seeds, are indeed two of the most widely used medicinals in Traditional Chinese Medicine, and modern research is now starting to bear out why.
For practitioners, a list of traditional formulas with xing ren (semen armeniacae) shows its widespread clinical use: Bu Fei E Jiao Tang (Tonify the Lungs with Ass-Hide Gelatin), Da Huang Zhe Chong Wan (Rhubarb and Eupolyphaga Pill), Da Qing Long Tang (Major Bluegreen dragon decoction), Ding Chuan Tang (Arrest Wheezing/Asthma Decoction), Huo Po Xia Ling Tang (Agastache, Magnolia, Pinellia and Poria Decoction), Ma Huang Lian Qiao Chi Xiao Dou Tang (Ephedrae, Forsythia and Aduki Bean Decoction), Ma Huang Tang (Ephedrae Decoction), Ma Xing Shi Gan Tang (Ephedrae, Apricot Kernel, Gypsum and Licorice Decoction), Ma Zi Ren Wan (Hemp Seed Pill), Qing Qi Hua Tan Wan (Clear Qi and transform Phlegm Expectorant Pill), Qing Zao Jiu Fei Tang (Eliminate Dryness and Rescue the Lungs Decoction), Ren Shen Ge Jie San (Ginseng and Geck Powder), San Ren Tang (Three Nut Decoction), Sang Ju Yin (Mulberry Leaf and Chrysanthemum Decoction), Sang Xing Tang (Mulberry Leaf and Apricot Kernel Decoction), Si Wu Ma Zi Ren Wan (Four Substances Cannabis Pill), Wu Hu Tang (Five Tiger Decoction), Wu Ren Wan (Five Seed Pill), Xing Su San (Apricot Kernel and Perilla Leaf Powder).
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