. 2022 Nov 28;12(1):20469.

doi: 10.1038/s41598-022-24309-z.

Cordyceps cicadae and Cordyceps gunnii have closer species correlation with Cordyceps sinensis: from the perspective of metabonomic and MaxEnt models

Min Zhang^{1

2}, Xiao Sun¹, Yujing Miao¹, Minhui Li^{3

4}, Linfang Huang⁵

Affiliations

¹ A Key Laboratory of Chinese Medicine Resources Conservation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.
² College of Pharmacy, Baotou Medical College, Baotou, 014040, China.
³ College of Pharmacy, Baotou Medical College, Baotou, 014040, China. prof_liminhui@yeah.net.
⁴ Inner Mongolia Hospital of Traditional Chinese Medicine, Hohhot, 010020, China. prof_liminhui@yeah.net.
⁵ A Key Laboratory of Chinese Medicine Resources Conservation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China. lfhuang@implad.ac.cn.

PMID: 36443322
PMCID: PMC9705360
DOI: 10.1038/s41598-022-24309-z

Cordyceps cicadae and Cordyceps gunnii have closer species correlation with Cordyceps sinensis: from the perspective of metabonomic and MaxEnt models

Min Zhang et al. Sci Rep. 2022.

. 2022 Nov 28;12(1):20469.

doi: 10.1038/s41598-022-24309-z.

Authors

Min Zhang^{1

2}, Xiao Sun¹, Yujing Miao¹, Minhui Li^{3

4}, Linfang Huang⁵

Affiliations

¹ A Key Laboratory of Chinese Medicine Resources Conservation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.
² College of Pharmacy, Baotou Medical College, Baotou, 014040, China.
³ College of Pharmacy, Baotou Medical College, Baotou, 014040, China. prof_liminhui@yeah.net.
⁴ Inner Mongolia Hospital of Traditional Chinese Medicine, Hohhot, 010020, China. prof_liminhui@yeah.net.
⁵ A Key Laboratory of Chinese Medicine Resources Conservation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China. lfhuang@implad.ac.cn.

PMID: 36443322
PMCID: PMC9705360
DOI: 10.1038/s41598-022-24309-z

Abstract

Cordyceps sinensis is a second-class nationally-protected medicinal fungus and functional food. Cordyceps sinensis resources are endangered, and finding new medicinal materials is a fast and economical way to meet the current demonstrated demand, which can effectively solve the shortage of C. sinensis resources. In this study, the metabolite characteristics of Cordyceps were comprehensively revealed by LC-QTOF-MS technology. The maxent model can be used to predict the habitat suitability distribution of Cordyceps and screen out the main climatic factors affecting its distribution. The correlation model between climate factors and chemical components was established by Pearson correlation analysis. Finally, based on the analysis of climate factors and metabolites, we will analyze the high correlation species with C. sinensis, and develop them as possible alternative species of C. sinensis in the future. The results showed that the suitable area of Cordyceps cicadae demonstrated a downward trend, while that of C. sinensis, Cordyceps militaris and Cordyceps gunnii demonstrated an upwards trend. The suitable areas all shifted to the northwest. The temperature seasonality and max temperature of the warmest month are the maximum climatic factors affecting nucleosides. Compared with C. sinensis, the metabolic spectrum similarities of C. cicadae, C. militaris, and C. gunnii were 94.42%, 80.82%, and 91.00%, respectively. Cordyceps sinensis, C. cicadae, and C. gunnii were correlated well for compounds and climate factors. This study will explore whether C. cicadae, C. militaris and C. gunnii can be used as substitutes for C. sinensis. Our results may provide a reference for resource conservation and sustainable utilization of endangered C. sinensis.

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Conflict of interest statement

The authors declare no competing interests.

Figures

**Figure 1**
PCA results of *C. sinensis*, *C. cicadae*, *C. militaris* and *C. gunnii* samples and quality control.

**Figure 2**
Species distribution point and sample photographs of *C. sinensis*, *C. cicadae*, *C. militaris* and *C. gunnii*. The figure was accomplished by ArcGIS (version 10.7, https://www.esri.com/zh-cn/arcgis/) and MaxEnt software (version 3.4.1, https://biodiversityinformatics.amnh.org/open_source/maxent/).

**Figure 3**
OPLS-DA model score diagram and model verification diagram of *C. sinensis*, *C. cicadae*, *C. militaris* and *C. gunnii* samples. (A) Score diagram of OPLS-DA model between *C. sinensis* and *C. cicadae*. (B) Score diagram of OPLS-DA model between *C. sinensis* and *C. militaris*. (C) Score diagram of OPLS-DA model between *C. sinensis* and *C. gunnii*. (D) OPLS-DA model verification diagram between *C. sinensis* and *C. cicadae*. (E) OPLS-DA model verification diagram between *C. sinensis* and *C. militaris*. (F) OPLS-DA model verification diagram between *C. sinensis* and *C. gunnii*.

**Figure 4**
Analysis of total metabolites in *C. sinensis, C. cicadae, C. militaris and C. gunnii*. (A) UpSet venn diagram for the total difference of metabolites between *C. sinensis, C. cicadae, C. militaris and C. gunnii*. (B) Pie chart of grouping proportion of total metabolites in the samples of *C. sinensis* (a), *C. cicadae* (b), *C. militaris* (c)*, C. gunnii* (d). (C) Cluster heat map of total metabolites in the samples of *C. sinensis, C. cicadae, C. militaris and C. gunnii*. (D) Volcanic map of total different metabolites between *C. sinensis* and *C. cicadae* (a), *C. militaris* (b), *C. gunnii* (c).

**Figure 5**
Analysis of nucleoside metabolites of Cordyceps. (A) venn diagram of nucleoside metabolites of *C. sinensis, C. cicadae, C. militaris* and *C. gunnii*. (B) Histogram of the relative contents of major components in nucleoside metabolites of *C. sinensis, C. cicadae, C. militaris* and *C. gunnii*. (C) Pearson correlation heat map of all metabolites of *C. sinensis, C. cicadae, C. militaris* and *C. gunnii.* (D) Pearson correlation heat map of nucleoside metabolites of *C. sinensis, C. cicadae, C. militaris* and *C. gunnii.*

**Figure 6**
(A) Analyze the interspecific correlation heat map of *C. sinensis*, *C. cicadae*, *C. militaris* and *C. gunnii* according to ecological climate factors. (B) The results of the Platts analysis of ecoclimate factors and nucleoside metabolites. (type1: ecoclimate factors, type2: nucleoside metabolites.) (C) Network diagram of correlations between eco-climate factors and nucleoside metabolites. (D) Correlation network diagram of eco-climate factors and major components in nucleoside metabolites.

**Figure 7**
ROC curve of MaxEnt model of *Cordyceps*. (A) ROC curve of MaxEnt model of *C. sinensis*. (B) ROC curve of MaxEnt model of *C. cicadae*. (C) ROC curve of MaxEnt model of *C. militaris*. (D) ROC curve of MaxEnt model of *C. gunnii*.

**Figure 8**
(A) Current situation and potential prediction of spatial suitability distribution of *C. sinensis* in China. (a) Histogram of urban area proportion in high (Class1) and medium (Class2) suitable distribution areas of *C. sinensis* in China at present. (b) Current map of suitable distribution areas of *C. sinensis* in China. (c–f) Map of suitable distribution areas of *C. sinensis* in China from 2021 to 2040, 2041 to 2060, 2061 to 2080 and 2081 to 2100. (B) Current situation and potential prediction of spatial suitability distribution of *C. cicadae* in China. (a) Histogram of urban area proportion in high (Class1) and medium (Class2) suitable distribution areas of *C. cicadae* in China at present. (b) Current map of suitable distribution areas of *C. cicadae* in China. (c–f) Map of suitable distribution areas of *C. cicadae* in China from 2021 to 2040, 2041 to 2060, 2061 to 2080 and 2081 to 2100. (C) Current situation and potential prediction of spatial suitability distribution of *C. militaris* in China. (a) Histogram of urban area proportion in high (Class1) and medium (Class2) suitable distribution areas of *C. militaris* in China at present. (b) Current map of suitable distribution areas of *C. militaris* in China. (c–f) Map of suitable distribution areas of *C. militaris* in China from 2021 to 2040, 2041 to 2060, 2061 to 2080 and 2081 to 2100. (D) Current situation and potential prediction of spatial suitability distribution of *C. gunnii* in China. (a) Histogram of urban area proportion in high (Class1) and medium (Class2) suitable distribution areas of *C. gunnii* in China at present. (b) Current map of suitable distribution areas of *C. gunnii* in China. (c–f) Map of suitable distribution areas of *C. gunnii* in China from 2021 to 2040, 2041 to 2060, 2061 to 2080 and 2081 to 2100. The figure was accomplished by ArcGIS (version 10.7, https://www.esri.com/zh-cn/arcgis/) and MaxEnt software (version 3.4.1, https://biodiversityinformatics.amnh.org/open_source/maxent/).

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Cordyceps cicadae and Cordyceps gunnii have closer species correlation with Cordyceps sinensis: from the perspective of metabonomic and MaxEnt models

Affiliations

Cordyceps cicadae and Cordyceps gunnii have closer species correlation with Cordyceps sinensis: from the perspective of metabonomic and MaxEnt models

Authors

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Abstract

Conflict of interest statement

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