Life Cycle Of Cordyceps

Cordyceps is composed of a fungus fruiting body and larva of the host, and its distribution is closely related to the distribution of the host. Many Cordyceps-related species have been found, which are based on different fungi growing on different insect hosts; however, most of them are not considered as Cordyceps for clinical usage except C. sinensis, which is listed in the Chinese Pharmacopoeia (3). China is the major producer of Cordyceps (4). In China, the parasitic complex of the fungus and the caterpillar is found in the soil of a prairie at an elevation of 3500-5000 meters, mainly in the provinces of Qinghai, Tibet, Sichuan, Yunnan, and Gansu (Fig. 2).

Cordyceps can grow on only a few species of insect hosts. At present, possible hosts of C. sinensis have been identified (5-19); they are listed in Table 1. An effective dispersal method of C. sinensis is important for the fungus to find the right host and to survive in nature; the fungus can be dispersed on a large scale through air, rain, and insects (Fig. 3). The host can be invaded in the larval state by C. sinensis that infects through the body wall, stoma, oral cavity, and/or orifices of the host. Another route of infection is

Figure 2 (A) The distribution of Cordyceps in China. (B) The parasitic complex of the fungus and the caterpillar is found in the soil of a prairie at an elevation of 3500-5000 meters, mainly in the provinces of Qinghai, Tibet, Sichuan, Yunnan, and Gansu (a and b). Freshly collected Cordyceps is shown in (c) and (d). Arrowhead in (c) indicates a living Cordyceps.

Figure 2 (A) The distribution of Cordyceps in China. (B) The parasitic complex of the fungus and the caterpillar is found in the soil of a prairie at an elevation of 3500-5000 meters, mainly in the provinces of Qinghai, Tibet, Sichuan, Yunnan, and Gansu (a and b). Freshly collected Cordyceps is shown in (c) and (d). Arrowhead in (c) indicates a living Cordyceps.

Biology of Cordyceps sinensis TABLE 1 Insect Hosts of C. sinensis

Ref. Species Ref. Species Ref

Species

Hepialus armoricanus 5

H. kangdingensis 6

H. yushuensis 6

H. oblifurcus 6

H. menyuanicus 6

H. sichuanus 6

H. baimaensis 7

H. pratensis 9

H. ferrugineus 10

H. jialangensis 12

H. anomopterus 12

H. luquensis 14

H. damxungensis 16

H. bibelteus 17

Hepialiscus sylvinus 18

Phassus giganodus 6

Magnificus zhiduoensis 19

H. devidi 6

H. varians 6

H. zhangmoensis 6

H. zhayuensis 6

H. kangdingroides 6

H. yulongensis 7

H. deqinensis 7

H. yunnanensis 9

H. jinshaensis 11

H. jianchuanensis 12

H. zhongzhiensis 13

H. xunhuaensis 14

H. bagingensis 16

Hepialiscus 6

nepalensis

Bipectilus 6

yunnanensis

Napialus humanesis 6

H. ganna 6

H. nebulosua 6

H. yunlongensis 6

H. lijiangensis 6

H. macilentus 6

H. meiliensis 7

H. renzhiensis 8

H. markamensis 9

H. albipictus 11

H. zaliensis 12

H. cingulatus 14

H. gonggaensis 15

H. latitegumenus 17

Hepialiscus flavus 6

Forkalus xizangensis 6

Magnificus jiuzhiensis 19

Figure 3 Host (H. armoricanus) can be invaded at the state of larva by C. sinensis. After the infection, Cordyceps fungus uses the bowels of the host as nutrient and starts to grow. After the host has died, the coarse mycelia will form a hard tissue. If the condition is suitable, the mycelia in the host will grow out through the oral cavity, and form the fruiting body, forming Cordyceps.

Figure 3 Host (H. armoricanus) can be invaded at the state of larva by C. sinensis. After the infection, Cordyceps fungus uses the bowels of the host as nutrient and starts to grow. After the host has died, the coarse mycelia will form a hard tissue. If the condition is suitable, the mycelia in the host will grow out through the oral cavity, and form the fruiting body, forming Cordyceps.

through food that is contaminated by C. sinensis mycelia or spores. After ingestion of contaminated food, C. sinensis invades the host through the digestive tract. The host body surface is also a route of fungus invasion. The insect body wall is composed of chitin, which can be hydrolyzed by an enzyme secreted by C. sinensis fungus, and thus the damaged body surface is available for fungus invasion. Penetration by mechanical pressure is another mechanism for fungal invasion (4).

Formation of Cordyceps can be divided into three stages: infection, parasitism (development of the fungus before insect death), and saprophyte (growth of the fungus after insect death). After infection, Cordyceps fungus makes use of the bowels of the host as nutrient and starts to grow. The mycelia creep over the insect body while the host is still alive. Subsequently, the color of the host body surface (shell) will fade in a few days from dark brown-yellow

Figure 4 Capillary electrophoresis profiles of water-soluble constituents from fruiting body and worm of natural Cordyceps. Condition: pressure injection 586 kPa for 5 sees, 57 cm x 75 pm ID column, running buffer 200 mM boric acid-sodium hydroxide (pH 8.5). The profile was monitored online at 254 nm, 0.100 AU at a data collection rate of 5 Hz for 40 mins. (A) Adenosine, (G) guanosine, (U) uridine. (Data modified from Ref. 20.)

Figure 4 Capillary electrophoresis profiles of water-soluble constituents from fruiting body and worm of natural Cordyceps. Condition: pressure injection 586 kPa for 5 sees, 57 cm x 75 pm ID column, running buffer 200 mM boric acid-sodium hydroxide (pH 8.5). The profile was monitored online at 254 nm, 0.100 AU at a data collection rate of 5 Hz for 40 mins. (A) Adenosine, (G) guanosine, (U) uridine. (Data modified from Ref. 20.)

and turn into light yellow; then the entire body is covered by gray mycelia. After the host has died, the coarse mycelia will form a hard tissue. If conditions are suitable, the mycelia in the host will grow out through the oral cavity and form the fruiting body, thus forming Cordyceps. The host loses its own biological and chemical characteristics, and eventually is invaded by C. sinensis mycelia. The collected Cordyceps have to be dried before they are sold on the market.

To determine the nature of the worm in Cordyceps, the biological activity and the main constituents of the fruiting body and the worm were investigated (20). The water extracts of the individual parts were analyzed by capillary electrophoresis and the content of nucleosides was determined. The fruiting body and the worm showed a close resemblance in their nucleoside peaks and overall profiles, while the dry naive worm with no Cordyceps mycelia showed a very distinct profile (Fig. 4). The nucleoside contents of the fruiting body and worm of Cordyceps were very similar. In addition, similar amounts of polysaccharides were found in the fruiting body and worm. The antioxidation activity of Cordyceps, from either the fruiting body or worm, was determined; the water extracts of the fruiting body and worm from Cordyceps had similar IC50 values in their inhibition of free-radical formation. On the other hand, the naive worm did not show any antioxidation activity in the range of mg/mL. These results suggest that the function of the worm in Cordyceps is to provide a growth medium for the fruiting body, and eventually, the worm is totally invaded by C. sinensis mycelia (20).

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