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Advances in Researches about Immunoregulatory Functions ofDendrobiumSw.

更新时间:2016-07-05

Supported by Special Fund for Basic Scientific Research Project in Chinese Academy of Agricultural Sciences "Research and Demonstration of Key Technology for Processing of Agricultural Products with Tibetan Characteristics".

1 Introduction

DendrobiumSw. (Orchidaceae) is perennial herb. In the world, there are about 1 500 species of Dendrobium, mainly distributed in tropical regions of Southeast Asia. In China, there are 74 species and two varieties of Dendrobium[1], mainly distributed in Yunnan, Guizhou, Sichuan, Guangxi, Guangdong, and Fujian. Dendrobium is traditional precious medicinal material in China[2]. It was first recorded in DivineFarmersClassicofMateriaMedica and was listed at the top of nine famous precious herbs. According to records of CompendiumofMateriaMedica, Dendrobium has functions of reinforcing yin essence and benefiting semen, and long time taking can improve the stomach and intestine; according to traditional Chinese medicine (TCM) theory, Dendrobium is sweet in taste, slightly cold in nature, belongs to stomach and kidney meridian, and has functions of promoting the production of body fluid and benefiting stomach, nourishing yin and clearing away heat[3]. ChinesePharmacopoeia 2015 received and recorded four species of Dendrobium: Dendrobiumnobile Lindl., DendrobiumofficinaleKimuraet Migo, Dctidrobiumchrysotoxum Lindl., and Dendrobiumfimbriatum Hook. Besides, Dendrobiumdevonianum Paxt.and Dendrobiumhuoshanense have high medicinal value.

Extensive researches have indicated that Dendrobium has regulatory effect on complex immune system. Some polysaccharides, alkaloids, and glycosides in Dendrobium have immune activity and can enhance or inhibit the body’s immune functions. We made an overview of the immunoregulatory functions and mechanism of Dendrobium, in order to lay a foundation for the further development and application of Dendrobium resources.

2 Regulatory effect ofDendrobium to the immune system

Through the immune system, the body can identify and eliminate alien antigenic substances, remove mutated tumor cells, senescent cells, and metamorphic cells, so as to maintain the relative stability of the body[4]. The immune system of the body consists of organs, cells and molecules, while the active components of Dendrobium can act on the body’s immune system[5-7].

2.1 Effects on immune organs The body’s immune reaction and immune function are realized through immune organs, and immune organs play an important role in the play of immunoregulatory function. From Dendrobium, Huang Minquan etal.[8] isolated three kinds of polysaccharides that have immune enhancement, can increase the weight of spleen and thymus of ICR mouse inbred lines, and can significantly proliferate T cells and B cells of the body. The crude polysaccharide extracted by Hou Shazhen etal.[9] from fresh Dendrobiumofficinale Kimura et Migo has a significant anti-inflammatory effect, can significantly reduce the xylene-induced ear swelling in mice, reduce the increase in peritoneal capillary permeability resulted from acetic acid, and inhibit the growth of granuloma induced by implantation of cotton pellets. Besides, crude polysaccharide of Dendrobiumnobile Lindl. also has anti-inflammatory effects[10], can significantly inhibit the permeability of capillaries, reduce leakage of capillary tissue fluid, and reduce bud tissue proliferation and platelet aggregation.

2.2 Effects on immune cells

2.2.2 The proliferation of lymphocytes. Immune cells are divided into T cells and B cells. The active components of Dendrobium promote the body’s immune function through regulation of T and B lymphocytes. Zhao Wushu etal.[14] found that polysaccharides of D. nobile Lindl. can promote mitosis of lymphocytes. The sesquiterpenoid glycosides in D. nobile Lindl. have two-way regulation effect of promotion and inhibition of invitro proliferation of mouse T and B lymphocytes, which is closely related to their components[15]. Han etal.[16] found that the phenanthrene component in the alcohol extract of D. nobile Lindl. could effectively inhibit the invitro proliferation and fibrosis activity of hepatic stellate cells. Gao Jianping etal.[17] carried out a comparative study on the immunoregulatory functions of the original medicinal materials and tissue cultured protocorm-like bodies (PLBs) of D. officinale Kimura et Migo, and the aqueous extracts of both have effect of improving the immune function, and the intensity of action is similar, and tissue cultured protocorm-like bodies can be used as excellent substitute for wild D. officinale Kimura et Migo.

2.2.1 The induction to macrophages. Active components of Dendrobium have different degree of regulation to natural killer cells (NK), macrophages and other immune cells. Studies have shown that D. nobile Lindl. decoction can promote growth of mouse spleen lymphocyte stimulated by Concanavalin A (ConA)[11], significantly promote phagocytosis of mouse macrophages[12], and delay the pathogenic lesions effect of enteric cytopathic human orphan virus ECHO11. At the same time, the phenanthrene and the bibenzyl components in the methanol extract of D. nobile Lindl. can inhibit the ability of LPS-induced mouse macrophage generating NO[13].

Extensive studies are concentrated on the antitumor effect of Dendrobium extracts[11], different extracts have different inhibitory effects. Lee etal.[24] found that ethyl acetate extract of D. nobile Lindl. can significantly inhibit the tumor cells (cancer cell A549, ovarian adenocarcinoma SK-OV-3, HL-60, and S-180), and the active components obtained through isolation and purification were phenanthrene compound; according to the study of Bao Lijuan etal.[25], the inhibition of aqueous extract of D. nobile Lindl. to tumor cells is correlated with the dosage, and it can inhibit, to a certain extent, the human cervical cancer cell line HelaS3 and hepatoma cell HepG2. Luo Wenjuan etal.[26] found that Crepidatin, chrysotobibenzyl and 4, 4’-Dihydroxypropyl-3, 3’, 5-Trimethoxy dibenzyl have different degree of inhibition to hepatoma cell line FHCC-98, and the function of Dihydroxypropyl-Trimethoxy dibenzyl is the most significant. In addition, polysaccharides of Dendrobium also have tumor suppression effect. Luo Huiling etal.[27] found that polysaccharides of Dendrobium can enhance the umbilical cord blood and improve the invitro killing effect of peripheral blood cells of cancer patients. Through the mouse Sarcoma 180 sarcoma inhibition experiment, Wang etal.[28] compared the biological activity of polysaccharides obtained by different extraction methods; the results indicated that tumor inhibitory activity of water-extracted crude polysaccharides was 31%, crude polysaccharides by alkali and acid extraction basically have no tumor inhibitory activity; further separation of crude polysaccharides of D. nobile Lindl. obtained six corresponding components; in Sarcoma180 sarcoma inhibition experiment of mouse, it found that water washing components and 0.1 mol/L NaCl eluted components showed higher inhibitory activity (up to 65% and 61%); through invitro experiments of human cervical cancer cell line HL-60 tumor cells, it found that polysaccharides components of D. nobile Lindl. obtained from all extraction methods showed cell proliferation inhibitory activity, and the inhibition was positively correlated with the dose.

The antitumor function of the body is closely related to its immunoregulation ability, and the immunomodulator plays an irreplaceable role in antitumor activities, and the antitumor function is realized generally through regulating the immune response cytokines[22-23].

3 Antitumor effect ofDendrobium

2.3 Effects on immune molecules Immune molecules are mainly antigens and antibodies, including immune proteins, immune factors, and interferon, they can regulate immune functions of the body and participate in a series of inflammatory reactions[18]. Inflammation is the body’s immune defense response to external stimuli. Experiments show that injecting the immunosuppressive agent cyclophosphamide into mice leads to a significant decline in leucocytes, polysaccharide of D. officinale Kimura et Migo. can promote generation of immune lymphocytes, and offset the side effects of cyclophosphamide-induced mobility suppression index[19]. Polysaccharides of D. nobile Lindl. can reduce the activity of NO synthase and reduce the amount of tumor necrosis factor and nitric oxide synthase secreted by mouse macrophages[20]. Using exogenous lipopolysaccharide, Zhang Junqing etal.[21] activated cerebral cortical astrocytes of rats. Through measuring the cell survival rate, protein of TNFα inflammatory cytokines and expression of inflammation-related genes TNFα and IL-6 mRNA, it indicated that the inhibition of total alkaloids of D. nobile Lindl. to anti-inflammatory mechanism of astrocytes is closely connected with the inhibition of activation of anti-inflammatory astrocytes and release of their inflammatory factors[21].

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Check Xueqiang etal.[34] compared the antioxidant activity of polysaccharides of D. huoshanense and D. officinale Kimura et Migo., and results indicated that both have different degrees of functions of scavenging invitro superoxide anion radical and hydroxyl free radicals, and also can be significantly acted in the linoleic acid oxidation system induced from alkyl free radicals.In addition, in the invitro antioxidant activity experiment, D. nobile Lindl. and Dendrobium moniliforme (L.) Sw.[35-36] have more significant functions.

4 Anti-aging effect ofDendrobium

这种“知”,还在于群体关系发生变化时经常出现的情感失衡和情感断裂。过去的乡情纽带和乡情联系还未结束,新的乡情意识和乡情认同还未形成,过去的文化、传统和历史不能够进一步维护社会秩序,也就无法对道德主体形成认知上的指示,自然也无法对道德行为进行有力的约束和实际的制约。在变化迅速的时代,群体间关系复杂不定,各种类型的“知行不一”或“知而不行”会产生人们产生种种道德失衡,道德焦虑就是其中一种重要的结果。这种无序和失衡对于乡村道德文化起着腐蚀、破坏的作用,也容易产生极大的隐患,使得当代乡村社会的道德秩序面临重建的必要性。

Using chemical method, Cai Yongping etal.[33] determined that D. huoshanense and other two kinds of Dendrobium directly contain highly active antioxidant enzymes, such as superoxide dismutase, peroxidase, catalase, and have a strong antioxidant capacity.

According to modern pharmacological studies, Dendrobium has a more significant invivo and invitro antioxidant and anti-aging effect. Active components of Dendrobium can bring into play the antioxidant effect through the following mechanisms. (i) Superoxide dismutase (SOD) is the primary substance, it can eliminate the harmful substances produced during the metabolism; active components of Dendrobium can significantly increase the SOD level, reduce lipid peroxidation (LPO), adjust the level of nerve mediators, and inhibit monoamine oxidase (MAO), and play the anti-aging role[29-31]. (ii) Direct reaction with within the body, H+ and OH- in Dendrobium polysaccharide C-H chain combine to form H2O, while C can react with to form oxygen free radicals, and finally it can be decomposed into matters not harmful for the body. (iii) Aerobic cells produce a series of reactive oxygen species (ROS) during metabolism. The active components of Dendrobium can complex metal ions (such as Fe2+, Cu2+, etc.) during the process of complexing, so that it can not produce ROS. Chen Zhuxia etal.[32] compared invitro antioxidant capacity (ability of scavenging superoxide anion and hydroxyl radicals) of 12 kinds of Dendrobium crude polysaccharide; except antioxidant capacity of crude polysaccharides of Dendrobium primulinum Lindl. and D. fimbriatum Hook. is not significant, other ten kinds of Dendrobium have different degrees of ability of scavenging superoxide anion.

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Shi Hong etal.[37] used rabbit to study the anti-aging effect of Dendrobium and found that after a period of feeding with Dendrobium, hydroxyproline (HYP) and SOD in the blood of rabbits were significantly increased, while LPO and MAO were significantly decreased, extracts of Dendrobium brought the anti-aging effect into play with the mechanism similar to the inhibition of monoamine oxidase. In the mouse model, Dendrobium extracts also have a more significant anti-aging effect. Through the models of D-Galactose induced sub-acute aging female mice and natural aging female mice, Liang Yingmin[38] compared the anti-aging effect of D. officinale Kimura et Migo., and results indicated that D. officinale Kimura et Migo. could significantly increase the antioxidant enzymes activity of the blood of mice, and improve the learning memory and imunity of mice, showing the anti-aging effect on the whole.

由此可见,转基因产品之所以引起人们的质疑,主要由于它涉及了人们对自身安全的担忧,尤其是与人们生活息息相关的吃的东西。一般而言,吃的东西都叫做食品,包括法律法规中的食品和部分农产品。但是,因为各种原因,一般国家在相关法律法规中,食品并不包括农产品。但是,我们在对转基因产品进行规范时,却不适合将两者分开规定或者舍弃某一部分,所以笔者认为,我们应该确立一个新的概念,即转基因产品。转基因产品既包括转基因食品包括的所有内容,也包括农业转基因生物中的所有内容,即转基因产品是指利用基因工程技术改变基因组构成,产生的用于农业生产或者农产品加工的动植物、微生物及其产品以及经过深加工的转基因食品。

Other components of Dendrobium, such as bibenzyl, phenolic acids and lignan, also have certain antioxidant activity. Zhang Xue etal[39] evaluated the antioxidant activity of bibenzyl and phenolic acids in 16 kinds of Dendrobium. The results showed that all the compounds have different degrees of free radical scavenging ability and oxygen radical scavenging ability, and the structure and activity of the compounds have significant structure activity relationship (SAR). In other words, the antioxidant activity of phenolic compounds to ferric thiocyanate is stronger than that of butylated hydroxyanisole (BHA)[40]; the phenanthrene and lignan components of D. nobile Lindl. also show strong invitro free radical scavenging ability, when there is methoxy in ortho-position of phenolic hydroxyl, the antioxidant activity of phenanthroline and lignan compounds significantly increases[41].

5 Prospects

Immune enhancers keep the body’s immune system in balance through regulating the immune system, including immune organs (spleen and thymus), immune cells (natural killer cells, lymphocytes, macrophages) and immune molecules (immune proteins, immune factors), so as to promote the body’s immunity. Polysaccharides, glycosides, alkaloids, and flavonoids are the main immune regulatory components of Dendrobium. The immune regulation of effective components is two-way, and there is significant difference in the immune regulatory ability of effective components of Dendrobium obtained by different extraction and isolation methods; for the same type of component, there is significant difference in regulatory ability for different immune tissues. The functional components of Dendrobium can effectively reduce inflammatory cytokines, inhibit tumor (cancer cells) and delay aging. In recent years, the researches on immune regulation of Dendrobium are extensive and in-depth. Functions of different varieties and different cultivation methods of Dendrobium are varied. The immune regulatory effect of Dendrobium will lay a solid foundation for the prevention and treatment of diseases. With more in-depth scientific researches, application, and exploration of modern biotechnology, Dendrobium as the immunomodulator will have a broad development prospect.

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国家之败,有事而无业,事则不经;有业而无礼,经则不序;有礼而无威,序则不共;有威而不昭,共则不明。不明弃共,百事不终,所由倾覆也。

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《Medicinal Plant》 2018年第2期
《Medicinal Plant》2018年第2期文献

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