What Are the Medical Uses of Cuttlefish Ink?

Substances extracted from ink sacs from sepia are named for their color and origin. The viscous suspension composed of fine black particles may be a proteoglycan complex connected to melanin, which contains a variety of active ingredients and has high medicinal value.

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As a traditional Chinese medicine, squid ink has long been recorded in the literature. "Compendium of Materia Medica" contains: "Ink in the abdomen, attending stabbing heartache." It is recorded in the "Book of Classics": "Convergent hemostasis, Gujing stop band, acid and pain relief, dehumidification and sore". Squid ink preparations are mainly used as hemostatic agents clinically to treat bleeding disorders such as functional uterine bleeding and gastric bleeding. There are three kinds of sepia inks that can be used for medicinal purposes in the Chinese Marine Medicine Dictionary, mainly Sepia subaculeata Sasaki, Sepia esculenta Hoyle, and Sepia andreana Steenstrup. They are distributed in southern Fujian, Guangdong, China The waters are also distributed in the Japanese waters. Fishing in the spring solstice and summer. After fishing, take squid ink sacs, tighten the sac mouth, dry or roast them, and prepare the ink powder in the ink sacs for future use. Usually squid ink is thrown away as waste. Since Japanese scholars discovered its antitumor activity, the research on squid ink has gradually increased, and many Japanese food companies have begun to use squid ink in food. [15] [16]

Antitumor activity of sepia

In the early 1990s, Japanese researchers demonstrated that squid ink can significantly inhibit or even eliminate the transplanted fiber malignant tumors in rats through animal experiments. At the same time, it is believed that this is not because squid ink directly acts on cancer cells, but kills it by improving immunity cancer cell. Lu Changlong et al. Observed the inhibitory effect of oral squid ink on the growth of transplanted tumors in mice, and found that squid ink significantly inhibited the growth of MethA and S180 sarcomas, with inhibition rates of 95.48% and 73.91%, respectively; To some extent, the formation of transplanted tumors was inhibited, and 67% (6/9) and 50% (5/10) of the mice in the two groups did not form tumors. Huang Mei's study on the antitumor effect of sepia ink showed that high, medium and low doses of sepia ink inhibited tumor weight of human liver cancer HHC15 nude mice by 82.2%, 70.1% and 35.5% (P <0.05), and There was a clear dose-dependent relationship. He Ye et al. Used fibroblast proliferation experiments to test the biological activity of sepia ink-induced macrophages to produce interleukin-1 (IL-1). The results showed that sepia ink can induce IL-1 production in BALB / C mouse macrophages. And the secretory activity is strong, there is a significant difference compared with the control group, the secretory activity is the highest at 48 hours. This result indicates that squid ink has a strong stimulating effect on macrophages, activates macrophages into effector cells, and participates in antitumor immunity. [17-20]
Zero / general / high-dose squid ink for tumor cells [21]
Xie Guanglin and others studied the inducing effect of squid ink on the natural killer (NK) cell activity of mouse spleen cells, and proved that squid ink can enhance the killing activity of NK cells in BALB / C mice, and that activated NK cells synthesize and secrete a variety of cytokines. Directly inhibit tumor cell differentiation and proliferation. At the same time, squid ink can also enhance the killing activity of NK cells in S180 and MethA tumor-bearing mice and shrink the tumor. NK cells have IL-2 affinity receptors on the surface. IL-2 can induce the activation and differentiation of NK cells, and IL-2 can activate tumor infiltrating lymphocytes (TIL). He Zheng et al. Detected the IL-2 secretion activity of mice induced by squid ink by MTT colorimetry, which suggested that squid ink caused the anti-tumor mechanism of NK cells. Wang Qun et al. Demonstrated that squid ink can significantly increase interferon- (IFN-) levels. IFN- is mainly produced by activated T cells and NK cells, and is also an active activator of NK cells, which can enhance the killing activity of NK cells and fully activate monocyte-macrophages. At the same time, their research also showed that squid ink activated lymphokine-activated killer cells (LAK) cells. [22-24]
In addition to the above-mentioned macrophages and NK cells as the main anti-tumor cellular immunity, red blood cell immunity also participates in the anti-tumor immune effect of sepia. Liu Chengyu and others examined the effects of sepia ink on the activity of red blood cell C3b receptors and the ability of red blood cells to adhere to tumor cells in normal and tumor patients. The results show that squid ink has the effect of activating red blood cell C3b receptor activity and enhancing the ability of red blood cells to adhere to tumor cells on red blood cells of normal people and tumor patients. This effect is accomplished by activating red blood cell C3b receptors. The mechanism of sepia ink's activation of C3b receptors in red blood cells may be that the polysaccharides in sepia ink bind to the thiol group of lymphocyte membrane C3b receptors and lymphocyte-associated antigen 3 (LAF-3), causing C3b receptor allosteries and increasing C3b receptor The cluster distribution of the body increases its activity. The enhanced C3b receptor activity of red blood cells not only enhances their ability to immunoadhesion tumor cells, but also increases the immune adhesion and killing effect of leukocytes on tumor cells, which plays an important role in preventing blood cells and lymph node metastasis of tumor cells. Sepia can also enhance the role of cellular immunity as a whole. Xie Guanglin and others orally administered squid ink to mice to determine the effect of squid ink on bone marrow cells in mice. The results showed that squid ink could induce multiple colony-stimulating factors in bone marrow cells of BALB / C mice, and promote the proliferation of bone marrow cells in vitro to form colonies. Multiple colony-stimulating factors can stimulate the proliferation and differentiation of pluripotent stem cells and various progenitor cells, promote the increase of granulocytes, monocytes and macrophages in tissues, thereby exerting anti-tumor effects. [25-26]
Protein kinase is a phosphotransferase that is closely related to the intracellular messenger system. Among them, tyrosine protein kinase (TPK), protein kinase C (PKC), and protein kinase A (PKA) are the most important. PKA is related to cell proliferation, while PKC and TPK are related to dedifferentiation. PKA and PKC play positive and negative regulatory roles in the Ras MAPK signaling system. Hou Xueyun and others used -32P-ATP as a reaction initiator to inject an exogenous substrate to determine the effect of sepia ink on the TPK, PKC and PKA activities of H22 cancer cells. The results showed that the TPK activity of cancer cells was significantly increased and the Membrane TPK activity increased most significantly, PKC activity increased significantly and nucleus PKC increased most significantly, and cytoplasmic PKA activity increased (probably a compensatory increase). After the action of squid ink, the TPK activity and PKC activity of cancer cells decreased significantly, while the cytoplasmic PKA activity continued to increase significantly, which inhibited the Ras MAPK signaling effect, suggesting that squid ink may be a protein kinase inhibitor. It is suggested that one of the antitumor mechanisms of squid ink may be to reverse the abnormal changes in the TPK, PKC and PKA activities of cancer cells, causing the inhibition of the Ras MAPK signaling system, and transforming cancer cells from dedifferentiated proliferation to differentiated proliferation, resulting in anti-cancer promotion. Differentiation effect. The c-fos and c-jun genes are both nuclear genes and belong to early response genes. They regulate gene transcription, cell division, differentiation and proliferation. In quiescent cells, if stimulated by mitogens, they can transiently enhance expression. Their expression is regulated by many signaling systems, especially by changes in Ca2 + levels. After administering squid ink to mice, Wang Chengbin et al. Used Fura 2 / AM fluorescent probe labeling, immunohistochemistry and biochemical methods to measure Ca2 + levels, nuclear membrane Ca2 + / Mg2 + -ATPase activity, and c-jun in H22 cancer cells. The changes in the expressions of c and fos showed that the level of Ca2 + decreased significantly with the increase of the dose. Compared with the control group, the two doses of sepia ink decreased the levels of Ca2 + by 69.4% and 78.6%, respectively. Significance. Decreased Ca2 + level will affect the Ca2 + -dependent Ca2 + / Mg2 + -ATPase activity in the nucleus. After testing the two doses of sepia ink, the enzyme activity decreased by 21% and 37%, respectively, thereby reducing the amount of Ca2 + into the nucleus. The transport weakened the effect of Ca2 + on the expression of c-fos and c-jun, and inhibited cell division and proliferation. [21] [27-28]

Sepia blood activity

According to the Chinese Dictionary of Marine Medicine, squid ink has hemostatic and menstrual effects, and treats functional uterine bleeding, hemoptysis, and menstruation. The dosage is 1-2 grams, twice daily. Tang Zangqi's "Compendium of Materia Medica" recorded the effect of squid ink as "main blood stabbing heartache." It is proved by modern clinical practice that it is a good systemic hemostatic drug, which has significant effects on various bleedings such as gynecology, surgery, and internal medicine, and has no side effects. For example, it has a good effect on bleeding caused by uterine bleeding, pulmonary tuberculosis, hemorrhage caused by gastrointestinal tract, inflammation, etc. It also has different degrees of efficacy on uterine bleeding, hematuria, hemoptysis of lung cancer, and bleeding of cervical cancer. In more than 0 patients with uterine bleeding, 67.5% of the patients received recent control after oral squid ink (bleeding stopped 5-7 days after starting the drug, and 42.1% of patients were cured after one or more cycles of treatment (5-7 days after drug administration) Bleeding stopped and no recurrence occurred within 3 months after discontinuation). This shows that squid ink can not only stop bleeding, but also improve systemic function through effective control of bleeding, and regulate the body's self-regulating function to restore function to normal. Observe 10 cases due to Bleeding caused by ulcer disease, gastritis, etc., was treated with squid ink, and the cure rate was 100%. The control group treated with intramuscular, vitamin K, and p-aminomethylbenzoic acid (PAMBA) intramuscularly or intravenously was cured, However, it is not as effective as squid ink. The average hemostatic days of squid ink is 5.8 days, compared with 8.6 days in the control group. Oral squid ink is used to treat tuberculosis hemoptysis. Of the 18 cases, 13 are invasive tuberculosis and 5 are hollow tuberculosis. , The average days of hemostasis is 6.8 days. The effect is obvious for long-term small hemoptysis, but not for large hemoptysis. For bronchiectasis, epistaxis, hematuria, lung cancer Blood, bleeding cancer also have a certain effect. [15] [29-30]
Xie Dameng and others proved that squid ink can shorten the clotting time of mice and significantly reduce the plasmin activity in rabbit serum, but it has no effect on the number of rabbit platelets. Therefore, the mechanism of hemostatic effect of sepia ink may be through inhibition of fibrinolytic enzyme activity, leading to a decrease in fibrinolysis, thereby promoting coagulation, and its coagulation effect may be related to the higher iron and calcium content in sepia ink. [31-32]
Squid ink has the effect of increasing white blood cells. After intraperitoneal injection of cyclophosphamide (50mg / kg) to mice for two consecutive days, it caused a sharp decrease in peripheral blood white blood cells. The treatment group used feed containing sepia ink to observe the number of white blood cells in the peripheral blood. (WBC). The results showed that the leukocytes of the treatment group that consumed the ink-containing feed picked up quickly, and returned to the normal range in advance, which were higher than the control group by 24.02% and 29.02% at 15-20 days, and returned to the original normal level 5 days earlier than the control group. . The Hb in the control group decreased slightly after the injection of cyclophosphamide. The addition of squid ink in the experimental group had no effect on the Hb. There was no significant difference in body weight between the treatment group and the control group before and after the experiment. It is suggested that squid ink can significantly promote the leukocyte reduction caused by cyclophosphamide. Wang Guang et al.'S study found that sepia polysaccharide can significantly increase the spleen index and anti-oxidative capacity of spleen tissue in mice injured by chemotherapy. The spleen SOD activity of the treatment group mice significantly increased, and the MDA content decreased significantly. Decreased bone marrow DNA content has a significant promotion effect, suggesting that the effect of squid ink on hematopoietic function can be through increasing the spleen tissue's antioxidant function, protecting the hematopoietic system from chemotherapeutic drugs, and alleviating the effects of chemotherapeutic drugs on bone marrow inhibition. According to studies by Chen Long and others, squid ink products can promote bone marrow hematopoiesis, and its action pathway may be through regulating the body's immune function, inducing the production of a variety of cytokines, promoting the proliferation of hematopoietic stem cells and granulocyte progenitor cells, and towards the granulocyte. Differentiation and promotion of myeloid hematopoiesis in mice. [33-35]

Antibacterial activity of sepia

Japanese scholars pointed out that adding squid ink to a marinated and fermented squid product can significantly improve the preservation performance of the product. The squid chemically added with squid ink showed a slow chemical change, and also showed significant differences in the micro-ecological environment during the maturation period, and the storage period was prolonged. Yamanaka et al. Also reported the antibacterial activity of squid ink. When squid meat was added with 3% squid ink during storage, its TVB-N content was lower than that of the control group without squid ink, and the storage period was significantly longer. Du Tieping obtained a light yellow hygroscopic powder from squid ink, which was confirmed to have antibacterial effect on Staphyloccocus aureus Rosenbach and Esaherichia coli by experiments, and the product was lysozyme active The test showed that it does not have lysozyme activity, and its antibacterial mechanism needs to be further explored. In the study of sepia polysaccharide, it was found that the small squid after soaking with sepia polysaccharide had a significantly longer shelf life during refrigeration. The pH value, the total number of colonies, volatile basic nitrogen and sensory scores were significantly better than the blank group. Sepia polysaccharide has a certain fresh-keeping effect. However, when studying the antitumor effect of sepia ink, its species and extraction conditions are not strictly limited. Are the ingredients and effects of sepia ink different in different seas, the same antitumor activity of different types of sepia ink, crude extracts and purified products of sepia ink? Whether there is any difference in the antitumor and immunoregulatory effects of the drug remains to be further studied. [12] [36-38]
Bacteriostasis of sepia extract (4 photos)
Effect picture and microscope picture of the antibacterial effect of sepia extract. [39-40]

Antioxidant effect of sepia

In addition to the direct damage to biological cells caused by ionizing radiation, reactive oxygen radicals such as superoxide anion free radicals and hydroxyl free radicals are mainly induced by indirect effects. Active oxygen free radicals are an important factor in damaging cells and tissues. They can cause DNA oxidation, breaks, or base mismatches in cells, and induce apoptosis. Studies by Chen Shiguo and others show that melanin in sepia ink has an important function of resisting the harm of photooxidation. It plays a role similar to superoxide dismutase, and can catalyze the conversion of O-2 to H2O2 and O2, thereby resisting photooxidation . Zhang Yongjun and others studied the effect of Fufangwuzimo capsule on SOD activity in mice. The results showed that the SOD activity in serum, liver and kidney of the three dose groups of aged mice was significantly higher than that of the control group and showed a good dose-response relationship. The SOD activity in the two dose groups of the mice in the group was significantly higher than that in the control group and had a dose-response relationship. The SOD activity in the liver and kidney was higher in the high dose group than in the control group. This result shows that the compound squid ink capsule can enhance the activity of SOD in serum and tissues, and has a better effect on the aging body. Wang Guang and others in the study of squid ink also found that squid ink can increase the SOD activity in the liver, spleen, myocardium and brain tissue of mice injured by chemotherapy, and reduce its MDA content, suggesting that the protective effect of squid ink on chemotherapy mice may be related to Related to increase the antioxidant capacity of organ tissues. [41-43]

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