Cordyceps sinensis
1、 Pharmacopoeia standard of Cordyceps sinensis       This product is a dry complex of the ascomycetes and larval corpses parasitized by the ergot fungus Cordyceps sinensis (berk.) sacc. on the larvae of bat moths. At the beginning of summer, when the spores are unearthed and not divergent, they are dug up, dried to 60% or 70% dryness, removed fibrous attachments and impurities, and dried in the sun or at low temperature.
      [character] this product is made by connecting the insect body with the fungal subplate growing from the insect head. The insect body is similar to silkworm, with a length of 3-5cm and a diameter of 0.3-0.8cm; The surface is dark yellow to yellowish brown, with 20-30 rings, and the ring near the head is thin; Head reddish brown; Foot 8 pairs, middle 4 pairs are more obvious; It is brittle, easy to break, with a slightly flat section, yellowish white. The pedestal is slender cylindrical, 4-7cm long, and about 0.3cm in diameter; its surface is dark brown to brown, with fine longitudinal wrinkles, and its upper part is slightly expanded; . The smell is slightly fishy and the taste is slightly bitter.
      [content determination] determine according to HPLC (general rule 0512).
      ; Octadecylsilane bonded silica gel was used as filler; The mobile phase was phosphate buffer (pH6.5) [68.5ml of 0.01mol/l sodium dihydrogen phosphate and 31.5ml of 0.01mol/l sodium dihydrogen phosphate, mixed (pH6.5)] - methanol (85:15); .
      Preparation of reference solution   .
      Preparation of test solution   Take about 0.5g of this product powder (passing through No. 3 screen), weigh accurately, place it in a corked conical flask, add 10ml of 90% methanol precisely, close the stopper, shake well, weigh, heat and reflux for 30 minutes, cool, weigh again, make up the lost weight with 90% methanol, shake well, filter, and take the filtrate.
      Assay   Precisely suck 10 µ l of the control solution and 10 µ l of the test solution respectively, inject them into the liquid chromatograph, and determine.
      The content of adenosine (c10h13n5o4) in this product shall not be less than 0.010%.
      [nature, taste and meridian tropism] sweet and smooth. Return to lung and kidney channels.
      [functions and indications] tonify the kidney and lungs, stop bleeding and resolve phlegm. It is used for kidney deficiency and essence deficiency, impotence and spermatorrhea, waist and knee soreness, long cough and asthma, cough and hemoptysis.
      [usage and dosage] 3 ～ 9g.
      [storage] store in a cool and dry place to prevent moths.


2、 Chemical constituents of Cordyceps sinensis
Cordyceps sinensis contains 25.32% crude protein, and the amino acids obtained from its hydrolysis areL-aspartic acid （L-Asparagine）， Glutamic acid,l-serine （L-serine），l-his （L-histidine），glycine（glucine），L-threonine（L-threonine），L-arginine（L-arginine），l-tyrosine （L-tyrosine），L-alanine（L-alanine），L-tryptophan（L-TCMLIByptophane），L-Methionine （L-methboine），L-valine （L-valine），L-phenylalanine（L-phenylalanine），L-isoleucine（L-isoleucine），l-leucine ,L-lysine（L-lysine）。 It also contains 8.4% fat, including 13.0% saturated fatty acids (stearic acid), 82.2% unsaturated fatty acids (oleic acid 31.69%, β - linoleic acid 68.13%). D-Mannitol（D-mannitol）， Vitamins A, C, B12, nicotinic acid, nicotinic amine,Ergosterol（ergosterol），Uracil（uracil），adenine（adenine），Adenine nucleoside（adenine nucleoside）， Ergosterol peroxide, cholesteryl palmitate and water-soluble polysaccharide galactomannan are composed of 1mol of D-galactose and 1mol of D-mannose respectively. It also contains a variety of trace elements, with the highest content of phosphorus, followed by sodium, potassium, calcium, magnesium, aluminum, manganese, iron, copper, zinc, boron, nickel, etc. Pre test also contains alkaloids. In addition to a large number of amino acids and mannitol, the near subplate part also obtained hypoxanthine nucleoside, thymine, uracil, and hypoxanthine mixture containing a small amount of guanine; Hypoxanthine, guanine,adenineAnd adenosine.

3、 Pharmacological effects of Cordyceps sinensis
1. immunopharmacological effects: 1.1. effects on immune organs: Cordyceps sinensis and Cordyceps militaris extract can significantly increase the spleen weight of mice and antagonize the reduction of spleen weight caused by prednisolone and cyclophosphamide. The mechanism may be through promoting the biosynthesis of spleen DNA, increasing the content of nucleic acids and proteins, and promoting the proliferation of spleen cells. Antagonizing the spleen atrophy caused by corticosteroids and cyclophosphamide is achieved by the effect of Cordyceps Polysaccharide on increasing the nutritional blood flow of spleen. Cordyceps sinensis and Cordyceps militaris extract can also shrink the thymus of mice and aggravate the thymic atrophy caused by prednisolone and cyclophosphamide, but the thymic atrophy caused by them is reversible. Histochemical analysis only showed that the medullary cells of atrophic thymus were slightly enlarged, loose and mitotic, but no inhibition phenomena such as tissue atrophy and cell destruction were found. Therefore, the thymic shrinkage caused by Cordyceps sinensis may be related to the effect of chasing and releasing. In mice with bilateral adrenals removed, the effect of Cordyceps sinensis induced thymic atrophy disappeared, indicating that this effect was achieved through the adrenal cortex. The components that cause thymus shrinking exist in both the body and the part of the subplate of Cordyceps sinensis. In addition, the liver of mice using Cordyceps and Cordyceps fungus will be mildly enlarged. This is mainly achieved by increasing the volume of hepatic ffer's cells, but has no obvious effect on the synthesis of DNA, RNA and protein in hepatocytes.
1.2. enhancing effect on the function of monocyte macrophage system: histological examination and immunohistochemical analysis showed that the peritoneal adhesion cells, splenic macrophages, liver Kupffer's cells increased in size, cytoplasm, nucleoplasm, and intracellular acid phosphatase activity increased in mice treated with Cordyceps or Cordyceps preparation, which were in a state of excitation. The liposome preparation of Cordyceps sinensis has a strong activating effect on cell wall diacyl peptide (MDP). . Carbon clearance test showed that Cordyceps and its preparation could significantly increase the blood carbon clearance rate and liver and spleen phagocytosis coefficient in mice. In vivo phagocytosis test proved that Cordyceps and Cordyceps can significantly improve the phagocytic index and phagocytic percentage of mouse peritoneal macrophages, and can resist the decrease of phagocytic function of membrane cavity macrophages caused by cortisone. They can also increase the number of Fc receptors on the surface of monocytes and macrophages, thereby enhancing their ability to recognize, process and transmit antigen information and the ADCC effect on target cells achieved through Fc receptors. In addition, Cordyceps can also participate in the regulation of immune response by stimulating mouse peritoneal adhesion cells to secrete high titers of IL. The mechanism by which Cordyceps and Cordyceps militaris activate the monocyte macrophage system is still unclear. It may be directly activating this system, or it may be achieved through various cascade activation including TLC and complement properdin system.
. Compared with the stimulatory effect of ConA on thymocytes, the effect of Cordyceps sinensis is not strong, and the stimulation index is only 1 / 56 of ConA. The effect of Cordyceps sinensis on splenocyte proliferation was related to the dose, and 8mg/ml was the optimal dose, but its effect was significantly lower than that of ConA. Mouse splenocytes were treated with anti thy-l serum and complement, and the 3H TDR incorporation method confirmed that T lymphocytes had been completely destroyed, but the treated cells still had proliferative response to Cordyceps sinensis stimulation, and the stimulation index was 18.6, indicating that Cordyceps sinensis had a direct stimulation of spleen thy-l cells, that is, B lymphocyte proliferation. The serum IgG content of mice treated with Cordyceps or Cordyceps polysaccharide increased significantly. Mice were given Cordyceps preparation, and the content of serum hemolysin after chicken blood cell rabbit epidemic was detected. The results showed that the half hemolytic value (HC50) of Cordyceps group was significantly higher than that of the control group (p< 0.01). The HC50 of Cordyceps mycelium powder 0.3ml, Ig mice, for 7 consecutive days, was 55.16% higher than that of the control group; 001, indicating that Cordyceps and its preparation can increase the serum hemolysin (IgM) level in mice. Cordyceps (8mg/ml) was incubated with splenocytes for 48 hours. After treatment, it could partially absorb and remove IL2 from the supernatant, and the absorption percentage was similar to that of ConA activated splenocytes, suggesting that Cordyceps can induce splenocytes to express IL2 receptors, and the number of IL2 receptors induced by Cordyceps is similar to that induced by ConA.
1.4. regulation of cellular immune function: Cordyceps or Cordyceps can inhibit the cellular immune function of the body. . They can also significantly inhibit (p< 0.01 = DNCB induced delayed hypersensitivity in mice. Cordyceps powder 0.6-5mg/ml could significantly inhibit the phagocytosis of peripheral leukocytes, proliferation of splenic lymphocytes, mixed lymphocyte culture and LPS induced IL-1 production of macrophages in mice (p< 0.05-0.01 =. The inhibition intensity was in positive proportion to the amount of Cordyceps powder. 5mg/ml Cordyceps powder could completely inhibit the above cellular immune response, and the dose of drug did not affect the survival rate of cells when co cultured with splenocytes for 5 days. The survival time (12.7 ± 2.2 days) of skin grafts in mice treated with Cordyceps powder 4g/kg daily was significantly longer than that in the control group (8.3 ± 0.7 days) (p< 0.01 =, similar to the effect of cyclosporine A (5mg/kg daily, PO) on inhibiting skin graft rejection (13 ± 2.9 days, P > 0.7). Cordyceps sinensis can significantly reduce the active E rosette (EA) formation rate of human peripheral blood T lymphocytes and prolong the survival of mouse allograft hearts. Using 3H TDR incorporation method to study the T lymphocyte subsets of mice, the results showed that Cordyceps could significantly enhance ConA induced suppressive T lymphocyte (TS) function in mice in vitro, and significantly enhance spontaneous suppressive T lymphocyte (STS) function in vivo, suggesting that it selectively acts on TS cell subsets to play a regulatory role on cellular immune function. However, the research results of Cordyceps and Cordyceps on the regulation of cellular immune function are not consistent, which may be related to drug treatment, animal selection and experimental methods. Therefore, some reports have reported that Cordyceps or Cordyceps fungus can enhance the cellular immune function of the body. . Rabbits taking Cordyceps ((2g/ (kg · day) for 7 days) were determined according to the 3H TDR incorporation method of PHA leaching test. The results showed that Cordyceps could promote T lymphocyte transformation. Cordyceps sinensis ethanol extract can increase the E-rosette formation rate of mouse lymphocytes, and antagonize the decrease of E-rosette rate caused by prednisolone and cyclophosphamide.
1.5. enhancing effect on natural killer cell (NK) activity: 125I release method was used to detect the NK activity in vitro of mice and humans, and 125I clearance method was used to detect the NK activity in vivo of mice. In vivo administration of Cordyceps sinensis alcohol extract could significantly enhance the killing activity of NK on YAC-1 cells in vivo and in vitro of mice, and protect the decrease of NK activity in immunosuppressive mice caused by cyclophosphamide; In vitro treatment of human peripheral blood mononuclear cells with 0.1 and 1.0mg/ml Cordyceps alcohol extract could enhance the activity of NK killing K562 cells in a time-dependent manner.
2. effect on central nervous system: 2.1. effect on spontaneous activity of mice: direct activity tracing method was used. The equivalent crude drug amount of IP Cordyceps sinensis extract was 5g/kg. The control group was treated with normal saline. Sj- Ⅲ physiological recorder was used to trace the curve of spontaneous activity of mice before and 30 minutes after administration. The results showed that Cordyceps group could significantly reduce the spontaneous activity of mice.
2.2. effect on the sleep time of mice caused by sodium pentobarbital: mice were given the above dose of Ig once a day for 4 consecutive days, and the control group was given equal volume of normal saline. One hour after the last administration, IP pentobarbital sodium 40mg/kg. The disappearance of righting reflex was taken as the sleep index, and the sleep time of each group was recorded. The Cordyceps group was 31.68 ± 12.88 minutes (n = 19, p< 0.05), and the normal saline group was 23.60 ± 9.44 minutes (n = 20). The artificially Fermented Cordyceps mycelium extract (CSB) can increase the sedative effect of chlorpromazine and antagonize the excitatory effect of amphetamine in mice. The effect intensity is related to the dose. 5g/kg can reduce the activity of mice by half. The sleep time of pentobarbital sodium could be significantly prolonged by ipcsb10-20g/kg in mice, and the P values were < 0.05 and p< respectively compared with the control group; 0.01.
2.3. anticonvulsant effect: mice were treated with different doses of artificially Fermented Cordyceps mycelium extract (code CSB), and 40 minutes after administration, each mouse was given 1.1mg/kg nicotine IV. results 10 / 10 animals in the control group developed tonic spasm and then died. The mortality rates of 5, 10, and 20g/kg dose groups of CSB were 5 / 10, 2 / 10, and 0 / 9, respectively, which were significantly lower than those of the control group.
2.4. effect on salivation caused by pilocarpine: mouse sccsb10, 20g/kg or normal saline. .
2.5. effect on the body temperature of normal animals: mice were injected with normal saline at sccsb5, 10 and 20g/kg, respectively. LH measured the anal temperature with a semiconductor thermometer. Results the anal temperature in the administration group were 36.89 ± 0.28, 35.99 ± 0.26 and 34.85 ± 0.31 ℃, which were significantly lower than those in the control group (37.98 ± 0.13 ℃) (p< 0.01). .
3. effects on the cardiovascular system: 3.1. effects on blood pressure and heart rate: anesthetized rabbits were given Artificial Cordyceps mycelium alcohol extract (CS-4 for short) and Artificial Cordyceps hair alcohol extract (Dongfa for short) at 0.15 and 0.3g/kg, respectively, to observe the changes of blood pressure and heart rate. The results showed that CS-4 ethanol extract significantly slowed down the heart rate of rabbits (p< 0.005) for more than 1 hour; The general trend of blood pressure decreased. At the dose of 0.3g/kg, the blood pressure decreased significantly within 5 minutes after administration (p< 0.01), but quickly returned to the original level. . When anesthetized dogs were treated with Cordyceps Extract (1:1) 0.5-1.0ml/kg, it had obvious hypotensive effect. During hypotension, the amplitude and frequency of respiration increased. However, IP or im had no effect on blood pressure when given 2ml/kg of 1:1 infusion.
3.2. effects on myocardial ischemia: Rabbits IV Artificial Cordyceps mycelium alcohol extract 0.3g/kg and Artificial Cordyceps fermentation liquid extract 0.1g/kg and 0.15g/kg, as well as equal volume saline or culture liquid as control. Five minutes later, i.v. pituitrin 1.5u/kg, and the electrocardiogram was recorded. The changes of S-T segment and T wave were taken as observation indicators. The results showed that the effect of alcohol extract on ECG was not statistically different from that of the control group (P > 0.05). The 0.1g/kg extract group could significantly resist the vertical rise of T wave (p< 0.05 = and resist the rise of 3-T segment). The alcohol extract also had a protective effect on stress-induced myocardial infarction in rats. The ethanol extract and extract were administered to mice at 2.5 and 5.0g/kgip. After 10 minutes, isoproterenol 300ug/kg was administered to determine the oxygen consumption and death time of mice. Results the alcohol extract could significantly prolong the survival time of hypoxic mice (p< 0.001) and improve the ability of hypoxia tolerance. At the same time, the oxygen consumption of mice in the administration group was significantly decreased (p< 0.05-0.001). The extract group also significantly prolonged the survival time of hypoxic mice (p< 0.001) and significantly reduced their oxygen consumption (p< 0.001 =), but the low-dose group only prolonged the survival time of mice.
3.3. antiarrhythmic effect: the ethanol extract of Artificial Cordyceps mycelium 0.5g/kg can significantly prolong the time of aconitine induced arrhythmia and shorten the duration of arrhythmia, and has statistical significance. The effect on arrhythmia induced by barium chloride could not prolong the time of arrhythmia induced by barium chloride, but could shorten the time of arrhythmia maintenance, with significant difference compared with the control group (p< 0.02).
. Results the serum cholesterol content of mice in each group was; 75.8 ± 12.8 (mg%) in Cordyceps group; The mycelia cultured by artificial fermentation group was 81.8 ± 10.8 (mg%), which was significantly different from 116.2 ± 7.5 (mg%) of the control group (p< 0.05). The results showed that both of them had the effect of reducing serum cholesterol. The ethanol extract of artificial Fermented Cordyceps mycelium had the effect of reducing cholesterol and b-lipoprotein in mice at the dose of 2.5g/kg. Compared with the control group, p< 0.01. Cordyceps sinensis fermentation broth Ig could significantly reduce plasma triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) in normal rats, while high density lipoprotein cholesterol (HDL-C) and HDL-C / TC ratio were significantly increased; It also significantly improved the increase of blood lipids in rats under stress caused by high-dose thyroxine and norepinephrine.
4. effects on the blood system: 4.1. promoting hematopoietic function: Cordyceps has a significant blood promoting effect. The spleen nodule formation test of mouse bone marrow hematopoietic stem cells (CFU-S) showed that the alcohol crystalline preparation of Cordyceps (containing a variety of amino acids, D-mannose and polysaccharide) IP could significantly increase the CFU-S yield and suicide rate, indicating that the preparation could change the cycle state of mouse bone marrow CFU-S, promote them from go phase to S phase, and thus promote CFU-S proliferation.
4.2. effect on platelets: the IM or Ig of Cordyceps sinensis and artificially cultured mycelium aqueous extract were 5g/kg and 10g/kg, respectively, which could increase the spleen coefficient, splenic megakaryocytes proliferation, and the number of platelets in blood. Electron microscopy showed that the ultrastructure of platelets generated by mice in the practical drug group was consistent with that of normal mice, and there were also increased particles, and the tubule system was relatively dense and developed. It was preliminarily confirmed that Cordyceps sinensis preparation promoted mouse platelet generation is closely related to promoting the proliferation, differentiation and maturation of splenic megakaryocytes. The number of platelets generated was not only increased, but also their ultrastructure was the same as that of normal mice. . Results the two preparations had obvious antiplatelet aggregation effect at the dose of 5-10mg/ml (p< 0.05-0.001 =, while the effect was not obvious at the low concentration of 1-2.5mg/ml.
5. effect on smooth muscle: the extract of this product has an inhibitory effect on isolated rabbit ileum and can significantly enhance the effect of epinephrine, but the inhibitory effect on isolated guinea pig intestine is weak, and it also has an inhibitory effect on isolated guinea pig uterus without pregnancy. It was also reported that Cordyceps militaris extract could significantly dilate the smooth muscle of isolated guinea pig trachea. The mixture of artificial Fermented Cordyceps sinensis stock solution and mycelium 3:1, given to mice Ig at 5.0g/kg, has a strong antitussive effect on ammonia fog induced cough, and the antitussive r value is 150%. It can significantly prolong the latent time of cough and reduce the number of coughs in mice. Compared with the normal saline group, the dosage of artificial insect prairie liquid at 5.0g/kg, P< 01, and its action intensity is close to codeine. 3: ; 01, its effect exceeded that of natural Cordyceps and Platycodon grandiflorum. The natural Cordyceps Extract can significantly dilate the isolated guinea pig bronchus, and the concentration of artificial Fermented Cordyceps Extract 5 × l0-3g/ml can also significantly relax the isolated guinea pig tracheal muscle caused by histamine, compared with the normal saline group p< 01), but the antiasthmatic effect was still less than that of aminophylline, and it had no obvious antiasthmatic effect on the overall guinea pig asthma induced by histamine and acetylcholine mixture, and the prolongation rate of latent time was only 57.89%.
6. effects on nucleic acid and protein metabolism: Cordyceps sinensis and cultured Cordyceps sinensis hyphae (referred to as hyphae) were respectively made into a hot infusion, and given to mice sc0.2ml/ mouse, once a day for 4 consecutive days, Cordyceps sinensis could significantly increase the weight of spleen, at the same time, it could increase the amount of DNA, RNA and protein incorporated into spleen by 3H TDR, 3h ur and 3H leucine, and had no effect on the DNA content in spleen, but increased the RNA content and decreased the protein content. It has no effect on the incorporation and content of DNA, RNA and protein in liver, nor on the protein content and incorporation of serum. Hypha has a similar effect.
7. anti inflammatory effect: the ethanol extract of artificially Fermented Cordyceps mycelium was given to mice at SC5, 10 and 20g/kg, and 0.05ml of 0.2% croton oil ether ethanol solution was coated on the left ear of each mouse. The test was conducted according to the routine treatment for 4 hours. Results the difference of ear weight in the treatment group (5, 10, 20g/kg) was 14.2 ± 2.9, 12.2 ± 1.3, and 4.3 ± 0.8mg/kg, which was significantly lower than that in the control group (21.1 ± 1.9mg/kg). Similar results were obtained in the experiments of tangrongjiang et al. . Results both groups could reduce the rat foot swelling induced by egg white, P< 01, but the action time of the latter was only about 1 hour.
8. antibacterial effect: the in vitro test showed that cordycepin had inhibitory effect on Staphylococcus, Streptococcus, Bacillus melioides, Bacillus anthracis, and porcine hemorrhagic sepsis. The decoction of this product has an inhibitory effect on fungi such as tinea mentagrophyte, dermatophyte flocculus, tinea gypsea, and tinea laniformis.
9. anti tumor effect: Cordyceps militaris aqueous solution has certain anti-tumor effect on S180 in mice, and the inhibition rate is 30-40% when sc5g/kg × 3-4 times; . Cordyceps showed no inhibitory effect on ESC and other tumor strains (U14, hep, Lewis, l7212, L7712, W256, Yoshida sarcoma). The effect of Cordyceps militaris aqueous solution on S180 was weaker than that of Cordyceps militaris. When ip5g/kg × 3, there was no tumor inhibition effect. When ip5g/kg × 9-12 times, the tumor inhibition rate was 25% - 67% after 3-4 weeks of observation. Cordyceps militaris also showed no anti-tumor effect on other tumor strains U14, P388, W256, etc. Cordyceps water can also enhance the antitumor effect of 6-mercaptopurine, while Cordyceps water can only enhance the antitumor effect of cyclophosphamide, but not 6-mercaptopurine. . The experiment also showed that the water extract of natural Cordyceps and Artificial Cordyceps mycelium had obvious inhibitory effect on the growth of Lewis lung cancer subcutaneously transplanted in mice, and the tumor inhibition rate was significantly different from that of the control group (p< 0.01), but there was no significant difference between natural Cordyceps and Artificial Cordyceps mycelium.
10. effect on respiratory system: Cordyceps and Cordyceps sinensis water extract have obvious bronchodilator effect, but have no antagonistic effect on histamine induced tracheal contraction. It was also reported that low concentration of Cordyceps and Cordyceps water extract had the effect of contracting isolated guinea pig trachea. It also has expectorant and antiasthmatic effects.
11. other effects: 11.1. androgen like effect: Cordyceps militaris has certain androgen like effect and anti estrogen like effect, which can regulate and restore sexual dysfunction.
11.2. anti aging effect: Artificial Cordyceps reduced the plasma nonessential amino acids in patients with chronic renal failure, and the ratio of essential amino acids to nonessential amino acids increased, which may be related to the supplementation of essential amino acids to improve nitrogen utilization. The effect of Cordyceps mycelium produced by three different factories on MAO-B activity in the brain of rats and mice was detected by radioisotope method. .