Research and Application of "The Three Treasures of Traditional Chinese Medicine" - Ejiao (Donkey-Hide Gelatin)

Ejiao (Donkey-Hide Gelatin) is a type of solid gelatinous medicine made from the fresh or dried skins of Equidae animals, specifically donkeys, through the processes of hair removal, soaking, boiling, and concentrating, with the addition of rock sugar and soybean oil as auxiliary ingredients. It is also known as Donkey Skin Gelatin. Ejiao is a traditionally valuable Chinese medicinal herb for enriching blood, characterized by its sweet taste and neutral nature. It possesses the effects of nourishing blood and nourishing yin, moistening dryness, and stopping bleeding, and is considered a "substance with emotional qualities."

First recorded in the "Shen Nong's Herbal Classic" (Shennong Bencao Jing), Ejiao is classified as a superior-grade medicine and is renowned as the "Holy Medicine for Enriching Blood." Ejiao, together with ginseng and pilose antler, is known as "The Three Treasures of Traditional Chinese Medicine." According to the pharmacopoeia, Ejiao is used to treat various conditions related to blood deficiency, such as pallor and yellow complexion, dizziness and palpitations, muscular atrophy and weakness, restlessness and insomnia, internal wind due to blood deficiency, dryness-induced coughing, chronic cough with blood-stained sputum, vomiting of blood, hematuria, bloody stool, metrorrhagia and metrostaxis, and bleeding during pregnancy. Additionally, Ejiao has the function of calming the fetus and preventing miscarriage.

Ejiao contains 74.56% to 84.94% protein, with gelatin being the most abundant and biologically active chemical component. Gelatin is a mixture of peptides and proteins resulting from partial collagen hydrolysis. Polysaccharides are another significant component in donkey skin, and so far, only dermatan sulfate has been isolated from Ejiao. Dermatan sulfate is a natural glycosaminoglycan, a type of linear polysaccharide widely found in animal connective tissues, composed of repeated disaccharide units of aminohexoses and uronic acids, along with their isomerized or sulfated residues.

Ejiao has a distinct, fishy odor. Analysis using gas chromatography-mass spectrometry (GC-MS) has identified a total of 23 volatile compounds contributing to this odor. These volatile compounds primarily include esters, ketones, halogenated hydrocarbons, heterocyclic compounds, and others. Furthermore, Ejiao contains various saturated and unsaturated fatty acids, as well as multiple trace metal elements, eight of which are essential for human health. Notably, Ejiao is rich in Zn, Fe, Mg, Cu, Sr, and other trace metals.

Processing of Ejiao

Ejiao in its raw form is typically blocky and hard in texture, offering good stability but posing challenges in dispensing and use. Its low bioavailability and greasy nature can adversely affect the digestive functions of the spleen and stomach if taken for an extended period. By processing Ejiao, it becomes easier to pulverize and digest, significantly enhancing its bioavailability. Therefore, most Ejiao used clinically is in its processed form (Ejiao Zhu). The processing methods of Ejiao can be divided into traditional and modern approaches. Traditional methods include stir-frying with clamshell powder (ge fen) and stir-frying with pollen typhae (pu huang). Modern methods, on the other hand, encompass oven drying, microwave processing, and vacuum drying.

The stir-frying method with clamshell powder (ge fen) is a processing technique that utilizes clamshell powder to transform Ejiao into Ejiao Zhu. This process not only corrects Ejiao's unpleasant odor but also eliminates its inherent greasy nature. Stir-frying with pollen typhae (pu huang) powder is another processing method that uses pollen typhae powder to create Ejiao Zhu. By stir-frying Ejiao with pollen typhae powder, it reduces the adverse effects on the digestive functions of the spleen and stomach while enhancing its hemostatic and blood vessel-stabilizing properties.

Modern processing methods primarily employ modern heating techniques. Among them, the oven drying method utilizes a constant-temperature electric oven to process Ejiao. Microwave processing utilizes microwave heating, while vacuum processing involves the use of a vacuum dryer. During vacuum processing, when the vacuum level reaches -0.08 MPa, the steam valve in the interlayer is opened, and heat is applied to maintain a steam pressure of -0.10 MPa for drying.

Functional Effects of Ejiao

Modern pharmacological research has demonstrated that Ejiao possesses a diverse range of functional effects beyond blood-enriching, hemostatic, immune-enhancing, anti-hypoxic, cold-resistant, and anti-fatigue properties. It also safeguards the brain, increases calcium intake, offers anti-shock protection, inhibits tumor growth, promotes bone healing, and contributes to beauty and skin nourishment.

1. Effects on the Cardiovascular System

Ejiao is effective in treating various blood disorders, exhibiting anti-hemorrhagic anemia and anti-hemolytic anemia effects. It significantly elevates red blood cells, hemoglobin, and white blood cells in mice with hemorrhagic anemia and possesses hemostatic properties.

Ejiao, as a renowned clinical blood-enriching medicine, has a history spanning over two thousand years. The theory of Ejiao improving hematopoietic microenvironment suggests that Ejiao contains microenvironmental substances similar to other embryonic-like tissues, which can enhance the hematopoietic microenvironment. Another theory posits that Ejiao's beneficial effects on hematopoietic stem cells may stem from its collagen content, while the glycosaminoglycans it contains are associated with cellular proliferation and tissue differentiation within the hematopoietic system.

Modern animal experiments have revealed that compound Ejiao syrup can significantly increase the number of peripheral blood cells and bone marrow mononuclear cells in mice, enhance their body weight, and reverse the atrophy of the thymus and spleen. Furthermore, Ejiao has been found to alleviate symptoms in pregnant women with thalassemia without affecting their iron levels.

The hemostatic effect of Ejiao is related to dermatan sulfate (DS). In the process of hemostasis and anticoagulation, the activity of glycosaminoglycans (GAGs) with anionic groups is directly proportional to their polymer length and the number of anionic polysaccharides bound to them, allowing for the regulation of blood coagulation status. Additionally, Ejiao's hemostatic effect is also attributed to its ability to reduce vascular wall permeability, increase platelet count, and facilitate platelet aggregation through the adhesion of collagen to the vascular wall.

2.Anti-tumor Effects

In vitro studies have shown that Ejiao-containing serum can enhance the induction of lymphocyte proliferation and activation by mitogens, increase the ratios of CD3 (T cells) / CD3-CD56+CD16+ (NK cells) and CD3+CD4+/CD3+CD8+, elevate the ratio of Th1 while reducing the ratio of Th2 cells, thereby strengthening the immune response of the body to tumor cells. In vivo studies have also indicated that Ejiao-containing compound formulations exhibit inhibitory effects on the growth of S180 sarcomas and Lewis lung cancer, significantly prolonging the survival time of tumor-bearing mice, promoting the recovery of immune function after radiotherapy/chemotherapy, and reducing mortality from secondary infections. Furthermore, they significantly enhance the phagocytic rate of peritoneal macrophages and lymphocyte transformation rate in mice, while reducing the toxic and side effects of 5-fluorouracil chemotherapy on H22 liver cancer in mice. Ejiao can improve the immune response of the body to tumor cells, alleviate the toxic and side effects of radiotherapy and chemotherapy on patients, facilitate the recovery of body functions after chemotherapy for cancer patients, and improve their quality of life.

3.Immune Regulatory Effects

Ejiao has the ability to enhance the immune system of the body. Research has found that after biomimetic enzymatic hydrolysis, Ejiao becomes more easily absorbed by the human body, thereby further intensifying its immune-boosting effects. Ejiao dates exhibit strong immunomodulatory effects, regulating the immune function, humoral immune function, and macrophage phagocytic function in mice. Ejiao significantly elevates the thymus index in immune-deficient model mice, increases the content of serum hemolysin, enhances delayed-type hypersensitivity and splenic lymphocyte proliferation, improves the phagocytic rate and phagocytic index of peritoneal macrophages in mice towards chicken red blood cells, raises the serum levels of cytokines IL-3 and IFN-γ, reduces IL-4 levels, and increases the IFN-γ/IL-4 ratio.

4.Anti-Fatigue Effects

Studies have shown that Ejiao can significantly extend the time for mice to swim with weights attached, markedly increase the levels of liver glycogen and hemoglobin in mice at rest, and reduce the production of blood lactate and serum urea nitrogen after exercise, indicating that Ejiao has the effect of alleviating fatigue and enhancing exercise endurance. Research speculates that the abundant pharmacologically active amino acids such as Gly, Glu, Asp, and Arg present in Ejiao are crucial active ingredients contributing to its anti-fatigue effects. A study conducted on BALB/C inbred male mice in a weighted swimming test revealed that the levels of serum lactate, malondialdehyde, creatine kinase, and lactate dehydrogenase were significantly reduced in the compound Ejiao syrup group, while hemoglobin, liver glycogen, and serum urea nitrogen levels increased significantly. Additionally, SOD and glutathione peroxidase activities were markedly enhanced, indicating that compound Ejiao syrup can effectively delay the onset of fatigue and improve the body's tolerance to fatigue.

5.Bone Repair Effects

Ejiao possesses the ability to increase bone density and promote bone healing. Ejiao calcium can enhance the levels of serum calcium and phosphorus in rats with osteoporosis and rickets models, elevate serum alkaline phosphatase levels, and increase the content of calcium, phosphorus, and bone density in the femur. Furthermore, Ejiao Xuegai Ping can significantly elevate the levels of serum calcium and phosphorus in rats with osteoporosis induced by retinoic acid, significantly improving bone condition. Ejiao's kidney-nourishing and bone-strengthening formula can delay bone loss, improve bone ultrastructure and bone strength, and increase the concentrations of PICP, OCN, 1,25(OH)2D3, and 25(OH)D3 in the serum of ovariectomized rats. Simultaneously, it upregulates the gene expression level of VDR in the kidney. This indicates that Ejiao's kidney-nourishing and bone-strengthening formula has a favorable preventive and therapeutic effect on osteoporosis in rats, with its mechanism of action involving multi-target, multi-pathway, and multi-link promotion of bone calcium and phosphorus metabolism, bone formation and bone remodeling, as well as inhibition of osteoclast proliferation, bone cell, and osteoblast apoptosis.

In recent years, despite the increasing production of Ejiao in China due to the country's thriving medical and healthcare industry and expanding foreign trade, the demand for Ejiao still cannot be fully met due to the limitation of its raw material, donkey hide. Therefore, there is an urgent need for scientific research and development to create new Ejiao products that can replace donkey hide. Furthermore, while some of the active ingredients in Ejiao have been studied, it remains unclear whether other components participate in certain biological functions. Thus, further research into its active components and pharmacological mechanisms is of great significance for the development of healthcare products and pharmaceutical resources, as well as for promoting Ejiao, which embodies the concept of "medicine and food sharing the same origin," to the world.

References

[1] Du Yibo, Fan Huirong, Yan Zhao. Research Progress on Chemical Constituents and Pharmacological Effects of Ejiao [J]. Journal of Tianjin Medical University, 2018, 24(03): 267-270.

[2] Wu Haiyan, Sun Jiaming, Zhang Hui. Research Progress of Ejiao [J]. Journal of Traditional Chinese Medicine, Jilin, 2016, 36(01): 57-60.

[3] Yi Na, Yang Hua, Wu Yong, Xu Fengxia. Research Progress on Pharmacological Effects of Ejiao [J]. World Latest Medicine Information (Electronic Version), 2017, 17(54): 12-15.

About the Author

Xiaonisha, a food technology professional holding a Master's degree in Food Science, is currently employed at a prominent domestic pharmaceutical research and development company. Her primary focus lies in the development and research of nutritional foods, where she contributes her expertise and passion to create innovative products.