Study on the four Qi of Pfaffia glomerata based on the metabolomics technology and comparison of Dangshen (Radix Codonopsis) in the equivalent substitution prescription

doi:10.19852/j.cnki.jtcm.20240521.001

Abstract

Abstract:

OBJECTIVE: To explore the four Qiof Pfaffia glomerata (PG) and endow this foreign folk herb with the properties of Chinese medicine, make it Chinese medicinal and localized, and could be used as a Chinese medicine.

METHODS: The normal group, six cold herb groups, six hot herb groups, six cool herb groups, PG prescription group (PGPG), and Dangshen (Radix Codonopsis) prescription group (CPPG) were prepared with corresponding concentrations of water extracts, these herb extracts were administered by gavage to Sprague-Dawley rats, and the 12 h urine at night on the 29th day of the SD rats in each group were collected, Liquid Chromatograph Mass Spectrometer system was used to analyze them, the best discriminant models for the medicinal properties of cold-hot and cold-cool were set up, so as to the medicinal properties of PGPG, CPPG and PG were predicted. Based on the Progenesis QI, Human Metabolome Database, Kyoto Encyclopedia of Genes and Genomes, MetaboAnalyst 5.0 database, we enriched metabolic pathway and classification mechanism of medicinal properties of cold-cool Chinese herbs and the molecular mechanism of PG prescription.

RESULTS: We established a best model of cold-hot herbal discrimination in the positive ion mode, then the probability that PGPG was predicted cold property was 88.9%. Furthermore, a model of cold-cool herbal discrimination was established, then the probability of PGPG containing the cool property was 77.8%. In addition, typical cold and cool herbs mainly affected nine biomarkers such as tyrosine-proline, (R)-3',7-Dihydroxy-2',4'-dimethoxyisoflavane in rats. The regulation trend of PGPG on markers was basically as same as the cool herbs and mainly involved in regulating the two pathways of cytochrome P450 and purine metabolism.

CONCLUSION: The results showed PGPG had a cool medicinal property as same as CPPG, and the regulation trend of PGPG on markers was consistent with cool herbs. Therefore, the medicine properties PG and CP should be consistent, and the Traditional Chinese Medicine property of PG was predicted to be neutral.

Key words: Pfaffia glomerata, medicinal properties of Chinese medicine, metabolomics, molecular mechanism, equivalent substitution

SONG Zhenguang, YANG Bin, WANG Fei, YAN Dongmei, ZHOU Xiaoqing, HUANG Liping, GAO Xuemei, LI Bin, HUANG Luqi. Study on the four Qi of Pfaffia glomerata based on the metabolomics technology and comparison of Dangshen (Radix Codonopsis) in the equivalent substitution prescription[J]. Journal of Traditional Chinese Medicine, 2024, 44(4): 713-721.

Figures/Tables 8

Figure 1 Stability heat map of urine QC samples A: stability heat map of QC in positive ion mode; B: stability heat map of QC in negative ion mode. QC: quality control; ESI: electrospray ionization; +: positive ion mode; -: negative ion mode; R2: coefficient of determination.

Figure 2 Establishment of the prediction model for cold-hot medicinal properties in positive ion mode A: the principal components analysis score plots of cold herb and hot herb group in positive ion mode. principal components analysis-X test for intra-group differences, blue dots are cold herbs, green dots are hot herbs. B: the best training set for distinguishing properties of cold-hot herbs in OPLS-DA model, blue dots are cold herbs, green dots are hot herbs. C: the Positive Ion OPLS-DA Model Permutation Test Diagram. OPLS-DA: Orthogonal Partial Least Squares-Discriminant Analysis.

Figure 3 Establishment of the prediction model for cold-hot medicinal properties in negative ion mode A: the principal components analysis score plots of cold herbs and hot herbs group in negative ion mode. principal components analysis-X test for intra-group differences, blue dots are cold herbs, green dots are hot herbs. B: the best training set for distinguishing properties of cold-hot herbs in OPLS-DA model under negative mode, the blue dots are cold herbs, and the green dots are hot herbs. C: the negative ion OPLS-DA model permutation test diagram. OPLS-DA: Orthogonal Partial Least Squares-Discriminant Analysis.

Figure 4 The distribution of PGPG in cold-hot discrimination model A: the distribution of PGPG in cold-hot discrimination model under positive ion mode, the green dots are hot herb, the blue dots are cold herb, the red dots are PGPG. B: the distribution of PGPG in cold-hot discrimination model under negative ion mode, the green dots are hot herb, the blue dots are cold herb, the red dots are PGPG. PGPG: Pfaffia glomerata prescription group.

Table 1 Prediction results of cold-hot medicine properties of PG prescription in the positive ion mode

Item	Samples	1	2	Accuracy (%)
Hot herbs	35	31	4	88.6
Cold herbs	38	7	31	81.6
CPPG	9	1	8	88.9
PGPG	9	1	8	88.9

Table 2 Comparison of PG prescription and CP prescription in cold-hot medicine property distribution area under positive ion mode

Item	Samples	1	2	3	Accuracy (%)
Hot herbs	35	34	4	0	97.14
Cold herbs	38	7	31	0	81.58
CPPG	9	1	0	8	88.89
PGPG	9	1	0	8	88.89

Table 3 The prediction results of cold-cool medicine properties of PGPG and CPPG in the positive ion mode

Item	Members	1	2	Accuracy (%)
Cool herbs	43	42	1	97.7
Cold herbs	38	5	33	86.8
CPPG	9	8	1	88.9
PGPG	9	7	2	77.8

Table 4 Change trend of biomarkers in cold herbs group, cool herbs group and PGPG

M/Z	RT (Min)	HMDB number	Name	Cold medicine group (n = 5)	Cool medicine group (n = 5)	PGPG
330.056	3.06	HMDB0000058	Cyclic AMP	↓^a	↓^a	↓
311.157	5.96	HMDB0029113	Tyrosyl-Proline	↑^b	↑^a	↑
302.135	12.5	HMDB0030717	(R)-3',7-Dihydroxy-2',4'-dimethoxyisoflavan	↓^a	↓^b	↓^b
384.113	5.04	HMDB0014390	Benzatropine	↓^a	↓^b	↓
119.076	16.26	HMDB0030647	Artemidinol	↑^a	↑^b	↑^b
670.41	15.06	HMDB0014602	Acitretin	↓^a	↓^b	↑
419.245	17.24	HMDB0041809	4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol	↓^b	↓^a	↓^a
705.363	15.71	HMDB0030389	Quebrachidine	↓^a	↓^a	↓
518.31	15.61	HMDB0012501	10,11-Dihydro-12R-hydroxy-leukotriene E4	↓^a	↓^a	↓

References 30.

1.	Franco RR, de Almeida Takata L, Chagas K, et al. A 20-hydroxyecdysone-enriched fraction from pfaffia glomerata (spreng.) pedersen roots alleviates stress, anxiety, and depression in mice. J Ethnopharmacol 2021; 267: 113599.
2.	Lian L, Feng Y, Li YW, et al. Two new triterpenes from the roots of Pfaffia glomerata. J Asian Nat Prod Res 2019; 21: 442-8. DOI PMID
3.	Carneiro CS, Costa-pinto FA, Da Silva AP, et al. Pfaffia paniculata (Brazilian ginseng) methanolic extract reduces angiogenesis in mice. Exp Toxicol Pathol 2007; 58: 427-31. PMID
4.	Fernandes NF, Martino-Andrade AJ, Dos Santos Lourenço AC, et al. Supplementation with pfaffia glomerata (sprengel) pedersen does not affect androgenic-anabolic parameters in male rats. J. Ethnopharmacol 2015; 161: 46-52. DOI PMID
5.	Ou M, Liu Y, Qin MZ, et al. Pharmacognostical study on domestic Pfaffia glomerata. Biotic Resources 2021; 43: 370-74.
6.	Wang XR, Cao TT, Tian XM, Wang H, Wang Y. Quantification of "cold-hot" medicinal properties of Chinese medicines based on primary metabolites and fisher's analysis. Comput Math Method M 2022; 2022: 5790893.
7.	Huang NN, Li J, Rao Gx, et al. Evaluation of Shengmaiyin (Dangshen recipe) quality based upon high performance liquid chromatography fingerprint and multiple chemical pattern recognition. Zhong Guo Yi Yuan Yao Xue Za Zhi 2021; 41: 2433-42.
8.	Li B, Huang L, Liu Z, et al, inventor. Traditional Chinese Medicine granules containing brazilian ginseng and its preparation method. China patent CN113952392A. 2022. Jan. 21.
9.	Wen Y, Li HW, Liu FB, Hou ZK. Research progress on the methodology for the quantification research of Traditional Chinese Medicine nature. Zhong Hua Zhong Yi Yao Za Zhi 2017; 32: 1181-3.
10.	Xia YS, Wei GH, Wang ZG, Fu XJ. Review on research methods of cold and heat property of Chinese materia medica. Zhong Hua Zhong Yi Yao Za Zhi 2021; 36: 990-2.
11.	Liu JX, Li JH, Du CH, Yan Y. Metabonomic study of biochemical changes in serum of PCPA-induced insomnia rats after treatment with Suanzaoren decoction. Zhong Guo Zhong Yao Za Zhi 2021; 47: 1632-41.
12.	Liu P, Liu SL, Tian DZ, Wang P. The applications and obstacles of metabonomics in Traditional Chinese Medicine. Evid Based Complement Alternat Med 2011; 2012: 945824.
13.	Huang CD, Chen YF, Li BT, et al. Traditional Chinese Medicine constitution discrimination model based on metabolomics and random forest decision tree algorithm. Evid-Based compl alt 2022; 2022: 3490130.
14.	Xing XY, Zhao YL, Kong WJ, et al. Thinking and practice of animal ethology in study of cold and hot nature of Traditional Chinese Medicine. Zhong Guo Zhong Yao Za Zhi 2011; 36: 519-24.
15.	Manoharan H, Rambola RK, Kshirsagar PR, et al. Aerial separation and receiver arrangements on identifying lung syndromes using the artificial neural network. Comput Intell Neurosci 2022; 2022: 7298903.
16.	Zhong Z, Huang YK, Huang QD, et al. Serum metabolic profiling analysis of gout patients based on UPLC-Q-TOF/MS. Clin Chim Acta 2021; 515: 52-60. DOI PMID
17.	Li ZY, Yang HJ, Tang SH, et al. Study strategies on medicinal properties of foreign medicine introduced to Traditional Chinese Medicine. Zhong Guo Zhong Yao Za Zhi 2019; 44: 2972-9.
18.	He RP, Ma RY, Jin Z, et al. Proteomics and metabolomics unveil Codonopsis pilosula (Franch.) Nannf. ameliorates gastric precancerous lesions via regulating energy metabolism. Front Pharmacol 2022; 13: 933096.
19.	Gong ZG, Zhang SY, Gu BC, et al. Codonopsis pilosula polysaccharides attenuate Escherichia coli-induced acute lung injury in mice. Food Funct 2022; 13: 7999-8011.
20.	Xin Y, Yu KC, Yu Y, Wang HJ. Filtration and qualification for target biomarkers of Traditional Chinese Medicine formula "Fuzi Lizhong decoction" acting on stomach ulcer by UPLC/Q-TOF MS. Pak J Pharm Sci 2022; 35: 519-28. PMID
21.	Wang LY, Wang C, Zhao DP, et al. Construction and application of modern research paradigm of new foreign introducing Traditional Chinese Medicine. Zhong Guo Zhong Yao Za Zhi 2020; 45: 967-77.
22.	Li AR, Li AQ, Deng ZJ, Guo JW, Wu HK. Cross-species annotation of expressed genes and detection of different functional gene modules between 10 cold and 10 hot-propertied Chinese herbal medicines. Front Genet 2020; 11: 532.
23.	Wang CD, Hou XJ, Zhao F, et al. Literature research and Traditional Chinese Medicine properties of aspalathus linearis. Zhong Guo Zhong Yao Za Zhi 2020; 46: 1960-6.
24.	Qian XY, Nie LX, Zhao H, et al. Discovery and molecular elucidation of the anti-influenza material basis of Banlangen granules based on biological activities and ultra-high performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry. J Ethnopharmacol 2022; 298: 115683.
25.	Li J, Li X, Liu XL, et al. Untargeted metabolomic study of acute exacerbation of pediatric asthma via HPLC-Q-Orbitrap-MS. J Pharm Biomed Anal 2022; 215: 114737.
26.	Shi N, Zheng QC, Zhang HX. Molecular basis of the recognition of cholesterol by cytochrome P450 46A1 along the major Access tunnel. Acs Chem Neurosci 2022; 13: 1526-33. DOI PMID
27.	Ma RW, Cheng LM, Song Y, et al. Altered lung microbiome and metabolome profile in children with pulmonary arterial hypertension associated with congenital heart disease. Front Med-Lausanne 2022; 9: 940784.
28.	Song MM, Sheng XJ, Zhang JR, et al. Homeostatic regulation of the aryl hydrocarbon receptor-cytochrome P 450 1a axis by Scutellaria baicalensis-Coptis chinensis herb pair and its main constituents. J Ethnopharmacol 2022; 297: 115545.
29.	Pedley AM, Benkovic SJ. A new view into the regulation of purine metabolism: the purinosome. Trends Biochem Sci 2017; 42: 141-54. DOI PMID
30.	Guo J, Wang JX, Lino K, Tomita M, Soga T. Quantitative and molecular similarity analyses of the metabolites of cold- and hot-natured Chinese herbs. Evid-Based Compl Alt 2021; 2021: 6646507.

[1]	YAN Jing, FENG Huimin, QIU Fang, WANG Haijun, YIN Luyun, JIN Xiaofei, ZHAO Jiyu, WANG Hongyang, YAN Xiaoqin. Effect on serum metabolomics of rats with premature ovarian insufficiency by Zhibian (BL54) through Shuidao (ST28) acupuncture [J]. Journal of Traditional Chinese Medicine, 2024, 44(4): 722-733.
[2]	WANG Xiang, HUANG Jianping, WANG Yupeng, WANG Qilong, JING Yajiang, ZHANG Gang, PENG Liang, GAO Jing, WANG Hongyan, YAN Yonggang. Differential metabolite analysis of the pharmacodynamic differences between different ratios of Dahuang (Radix Et Rhizoma Rhei Palmati)-Taoren (Semen Persicae) herb pair [J]. Journal of Traditional Chinese Medicine, 2024, 44(3): 515-523.
[3]	JING Wenguang, LIN Xiaoyu, LI Chu, ZHAO Xiaoliang, CHENG Xianlong, WANG Penglong, WEI Feng, MA Shuangcheng. Anti-inflammatory mechanism of the non-volatile ingredients originated from Guanghuoxiang (Pogostemonis Herba) based on high performance liquid chromatography-heated electron spray ionization-high resolution mass spectroscope and cell metabolomics [J]. Journal of Traditional Chinese Medicine, 2024, 44(2): 260-267.
[4]	LI Chaoran, YANG Yan, FENG Chuwen, LI Heng, QU Yuanyuan, WANG Yulin, WANG Delong, WANG Qingyong, GUO Jing, SHI Tianyu, SUN Xiaowei, WANG Xue, HOU Yunlong, SUN Zhongren, YANG Tiansong. Integrated 'omics analysis for the gut microbiota response to moxibustion in a rat model of chronic fatigue syndrome [J]. Journal of Traditional Chinese Medicine, 2023, 43(6): 1176-1189.
[5]	WANG Miao, ZHU Yan, ZHAO Hui, ZHAO Hongfang. Moxibustion enables protective effects on rheumatoid arthritis-induced myocardial injury via transforming growth factor beta1 signaling and metabolic reprogramming [J]. Journal of Traditional Chinese Medicine, 2023, 43(6): 1190-1199.
[6]	JIANG Wenjing, JIANG Huaying, YUAN Lihua, SA Yuanhong, XIAO Jimei, SUN Hongqi, SONG Jingyan, SUN Zhengao. Xiaoyi Yusi decoction (消异育嗣汤) improves in vitro fertilization and embryo transfer outcomes in patients with endometriosis [J]. Journal of Traditional Chinese Medicine, 2023, 43(5): 1026-1033.
[7]	LIU Di, ZHANG Yingqi, YU Tianyuan, LIU Zhifeng, JIAO Yi, WANG Hourong, XU Yajing, GUAN Qian, CHEN Lulu, HU Hui. Protective mechanisms of Tuina therapy against lipopolysaccharide-induced fever in young rabbits based on untargeted metabolomics analysis [J]. Journal of Traditional Chinese Medicine, 2023, 43(4): 725-733.
[8]	XUE Nannan, JIA Liyang, LI Qiyan. Potential of natural medicines for treatment of osteoporosis: a narrative review [J]. Journal of Traditional Chinese Medicine, 2023, 43(1): 198-204.
[9]	QIAO Nan, WANG Qinnan, MA Chaoqun, CHEN Dexuan, CHEN Haidong, LU Yaoyao. Mechanism underlying efficacy of Shugan Sanjie decoction (疏肝散结汤) on plasma cell mastitis, based on network pharmacology and experimental verification [J]. Journal of Traditional Chinese Medicine, 2022, 42(3): 400-407.
[10]	HONG Zongchao, CAI Quan, DUAN Xueyun, YANG Yanfang, WU Hezhen, JIANG Nan, FAN Heng. Effect of compound Sophorae decoction in the treatment of ulcerative colitis by tissue extract metabolomics approach [J]. Journal of Traditional Chinese Medicine, 2021, 41(3): 414-423.
[11]	Liu Mi, Shen Jiacheng, Liu Caichun, Zhong Huan, Yang Qing, Shu Wenna, Ma Mingzhu, Dong Jiyang, Yang Zongbao, Chang Xiaorong, She Chang, Yu Shu. Effects of moxibustion and acupuncture at Zusanli(ST 36) and Zhongwan(CV 12) on chronic atrophic gastritis in rats [J]. Journal of Traditional Chinese Medicine, 2020, 40(5): 827-835.
[12]	Lai Xiaohua, Xiu Chengkui, Wang Xue, Fang Jingyi, Yang Jing, Lei Yan. Efficacy of Renshen Sanqi Chuanxiong formula for preventing vascular aging [J]. Journal of Traditional Chinese Medicine, 2019, 39(06): 780-793.
[13]	Feng Xuanchao, Yang Zheng, Chu Yuguang, Du Bai, Su Mei, Li Yi, Wang Yinghong, Jiang Chunying, Hu Yuanhui. ~1H nuclear magnetic resonance-based metabolomic study on efficacy of Qingrehuatan decoction against abundant phlegm-heat syndrome in young adults with essential hypertension [J]. Journal of Traditional Chinese Medicine, 2015, 35(01): 28-35.
[14]	Yin Zhang, Shaodan Li, Ke Cao, Yu Feng, Xiao Zhang, Yueyong Xiao, Jie Li. Mechanism research on combination of decoction for reinforcing lung Qi and argon helium lancet in treatment of non-small cell lung cancer [J]. Journal of Traditional Chinese Medicine, 2013, 33(03): 307-311.

Home

Online First

Author Center

Reviewer Center

Issues

Announcement

About Us