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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES · 2025 · IF 2.8

Total ginsenosides from wild ginseng improve immune regulation in a rat model of spleen qi deficiency by modulating fecal-bacteria-associated short-chain fatty acids and intestinal barrier integrity

Ruobing Bai,Liting Ma,Fangtong Li,Lijia Pan,Yuwen Bao,Xinze Li,Shen Wang,Hao Yue,Fei Zheng

For thousands of years, traditional Chinese medicine (TCM) has made extensive use of wild ginseng. It is thought to provide vital energy effects and to boost immunity. This study aimed to clarify the processes by which short-chain fatty acids (SCFAs) metabolites and the intestinal barrier are used by total ginsenosides wild ginseng (TWG) to modulate immunity. In this study, we analyzed and identified ginsenosides in the colon using UPLC-Q-TOF-MS E methods. In the meantime, a rat model of spleen qi deficiency (SQD) was created using reserpine, and the effects of TWG on intestinal barrier function and short-chain fatty acids in the feces of SQD-affected rats were examined. 28 ginsenosides were found in the colon during this experiment, and the main components were measured. TWG considerably increased fecal concentrations of acetic, propionic and 6 others, according to SCFAs analysis. According to serum immunological markers, TWG reduced IL-17 and IL-1β levels, increased IL-10, IL-22, and TGF-β concentrations, balanced Th17/Treg ratios, and reduced toxicants such DAO and LPS in rats with SQD. TWG improved barrier function, reduced permeability, increased tight junction protein expression, and lessened intestinal injury. A favorable correlation between intestinal barrier proteins and fatty acids was shown by correlation studies. The gut barrier and SCFAs perspectives helped to clarify the mechanism by which TWG controls immune activity. This study offers a fresh theoretical framework for TWG's future advancement and application.

CAS / MDL: 64-18-6
研究领域: 中医药学 · 免疫学 · 胃肠病学 · 微生物组研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Modulating the intestinal flora involves the effect of Atractylodis macrocephalae Rhizoma polysaccharide on spleen deficiency diarrhea

Shiru Huang,Han He,Hanxi Li,Chongyang Li,Fu Wang,Yuan Hu,Youping Liu,Lin Chen,Hongping Chen

Atractylodis macrocephalae Rhizoma (AM), a widely used Chinese herb for treating spleen deficiency diarrhea (SDD), is rich in polysaccharides. However, the precise mechanism underlying the antidiarrheal effects of Atractylodis macrocephalae Rhizoma polysaccharide (AMP) remains unclear. In this study, AMP, with a molecular weight of 69 kDa, is isolated from AM and consists of Glc, Gal, and Ara in a molar ratio of 84.16:6.51:9.33. FTIR and NMR analyses indicate that AMP features a linear backbone of →4,6)-α-D-Glc p -(1→ with branches of →3)-β-D-Glc p -(1→, terminating in →2,4)-β-D-Gal p -(1→. Animal models of SDD induced by Folium sennae demonstrate that AMP alleviates diarrhea symptoms, mitigates colon damage, and enhances spleen index, thymus index, and the expression of CD4 + CD25 + Foxp3 + Treg cells. Further, the potential mechanisms for AMP's antidiarrheal action are explored through the comprehensive approach integrating intestinal flora, polysaccharide utilization loci, short-chain fatty acids (SCFAs), and metabolomics. AMP reduces the abundance of pathogenic c_ Clostridia while promoting beneficial o_Bacteroidales and f_Muribaculaceae, influencing SCFAs production via its strong binding affinities with SusD, GH2, and GH43. This modulation is linked to alterations in linoleic acid metabolism, alpha-linolenic acid metabolism, and primary bile acid biosynthesis. In conclusion, AMP demonstrates significant potential as a therapeutic agent for SDD.

CAS / MDL: 103616-89-3
研究领域: 药理学 · 微生物学 · 免疫学 · 代谢组学 · 中医药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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NEUROGASTROENTEROLOGY AND MOTILITY · 2024 · IF 3.5

Polysaccharide extracted from Atractylodes macrocephala improves the spleen deficiency constipation in mice by regulating the gut microbiota to affect the 5-HT synthesis

Lei Chen,Xiangbing Chang,Chuntao Wu,Guofu Luo,Peifeng Zhang,Wei Tian

Background The traditional herbal medicine Atractylodes macrocephala Koidz. ( A. macrocephala ) is commonly utilized for alleviating symptoms associated with spleen deficiency, abdominal distension, diarrhea, and constipation. These pharmacological effects are attributed to a variety of active constituents. However, the specific bioactive compounds responsible for promoting defecation and gastrointestinal transit in A. macrocephala remain unidentified. Methods The primary polysaccharide characteristics of PAMK was elucidated by HPLC, FT-IR, and HGPGC. Efficacy of PAMK (0.07, 0.14, and 0.28 mg/g) on mice was evaluated in a spleen deficiency constipation mouse model by analyzing stool parameters, constipation-related physiological indexes, and SCFAs. The expression levels of 5-HT 3 R, 5-HT 4 R, and related receptor genes were examined by RT-qPCR, and neurotransmitters were examined using ELISA. Finally, the diversity of gut microbiota was analyzed with 16S rDNA sequencing. Key Results The results showed that PAMK significantly reduced the gastrointestinal transport time and increased the number of fecal pellets and fecal water content in spleen deficiency constipation model mice. PAMK kept the balance of 5-HT, SCFAs, TPH-1, SERT, CgA, and neurotransmitter levels (VIP, SP, MTL) in mice colon. In addition, PAMK could regulate the abundance of gut microbiota such as Alistopes , Bacteroides , and Odoribacter in spleen deficiency constipation model mice gut. Conclusions and Inferences It can be concluded that PAMK effectively ameliorated the symptoms of spleen deficiency constipation in mice by modulating the expression of 5-HT and its associated receptors. The underlying mechanism was elucidated, providing a solid theoretical foundation for the therapeutic application of A. macrocephala in treating spleen deficiency constipation and offering potential for developing novel approaches to address this condition.

研究领域: 药理学 · 胃肠病学 · 微生物学 · 中医
✓ 已验证 产品关联 DOI PubMed 高影响因子
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PHYTOMEDICINE · 2024 · IF 6.7

Insights into Q-markers of honey-fried licorice in treating spleen deficiency based on substance and energy metabolism regulation

Wenxin Xia,Yushu Wang,Jiahui Yue,Xueyan Fu

Background Honey-fried Licorice (HFL) is a dosage form of Glycyrrhizae Radix et Rhizome processed with honey, which has been recorded to exhibit better efficacy in tonifying the spleen compared to the raw product. In contrast, different processing methods of Glycyrrhizae Radix et Rhizome exhibit different efficacies and applications, but their current quality control index components remain consistent. Purpose Based on the discovery and research strategy of traditional Chinese medicine decoction piece quality marker (Q-marker), this study aimed to conduct a multidimensional integration of constituents absorbed into the body and metabolomics based on the tonifying spleen and stomach effects of HFL to effectively identify the Q-marker of HFL. Methods In this study, a spleen deficiency rat model was established using the "exhausted swimming + poor diet" method to investigate the pharmacodynamics of tonifying the spleen and stomach by HFL. The constituents absorbed into blood was conducted using UPLC-Q-TOF/MS, correlation analysis between metabolomics and constituents absorbed into blood recognized the Q-Marker of HFL. Results The pharmacodynamic data demonstrated that HFL exhibited a significant regulatory effect on the disordered levels of PP, trypsin, chymase, PL, α-Glu, MTL, GAS, VIP, IL-2, IFN-γ, and IgA in the spleen deficiency model. Furthermore, HFL was found to improve the pathological changes in the spleen and intestine in the spleen deficiency model, highlighting its significant "tonifying spleen and stomach" effect. In the serum containing HFL, a total of 17 constituents were identified as being absorbed into the blood. Among these, 11 were prototypical components, while 6 were metabolites. Metabolomics data revealed that 9 differentially expressed metabolic markers were observed. Furthermore, the analysis of endogenous metabolic markers indicated that 10 components exhibited significant correlations with these biomarkers. Conclusion The effect of "tonifying spleen and stomach" of HFL is closely related to the regulation of the material and energy metabolism pathway. The Q-Marker of HFL is glycyrrhizic acid and 18 β -glycyrrhetinic acid as the main control standards and liquiritin, isoliquiritin, liquiritin, isoliquiritin, isolicorice flavonol, licorice chalcone C and Formononetin were used as auxiliary standards.

研究领域: 中药学 · 药理学 · 代谢组学 · 药学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2025 · IF 3.1

Comprehensive Analysis of the In Vivo and In Vitro Metabolism of Guishao Yigong Decoction Based on UPLC-Q-TOF/MS

Wenwen Zhou,Xiaoxiao Zhang,Meijuan Liu,Meiyu Wan,Shu Jiang,Erxin Shang,Jinao Duan

Guishao Yigong Decoction (GYD), a classic prescription that tonifies the spleen and qi, has been used in clinical practices for thousands of years to treat spleen deficiency. However, its in vitro and in vivo metabolic characteristics are still unclear. In this study, a rapid and reliable analytical method based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) with automated data processing (MetaboLynx) was established to investigate the metabolites and metabolic pathways of GYD in vivo and in vitro . Based on the characteristics of protonated ions, eleven precursors (ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, atractylenolide I, atractylenolide III, paeoniflorin, glycyrrhizic acid, pachymic acid, liquiritin, nobiletin, and ferulic acid) and their corresponding metabolites were detected and tentatively identified. A total of 81 metabolites were identified, including 53 metabolites in vivo , 40 metabolites of liver microsomes, and 43 metabolites of intestinal flora in vitro . Distinct metabolic patterns were observed between intestinal flora and liver microsomes - the former primarily catalyzed phase I transformations (hydroxylation, methylation, dehydroxylation, demethylation, and reduction), while the latter also executed phase II metabolism, with glucuronidation being the predominant conjugation reaction. The metabolic profiling and pathways of active components in GYD were systematically analyzed, which was helpful in clarifying its potential mechanism and clinical application.

CAS / MDL: 64-18-6
研究领域: 药理学 · 植物化学 · 代谢组学 · 中医药学 · 药物代谢
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES · 2020 · IF 3.004

A metabonomics and lipidomics based network pharmacology study of qi-tonifying effects of honey-processed Astragalus on spleen qi deficiency rats

Li Huang,Mingzhu Ye,Jiacai Wu,Wuping Liu,Hongyuan Chen,Wen Rui

Honey-processed Astragalus is a dosage form of radix Astragali processed with honey, which is deemed to contain better qi-tonifying effects in traditional Chinese medicine theroy. Our previous study has demonstrated that honey-processed Astragalus exhibited a better effect on reinforcing qi (vital energy) and immune improvement toward spleen qi deficiency compared with radix Astragali. However, the detailed mechanisms related to qi-tonifying effects of honey-processed Astragalus is still unclear. In this study, we evaluated the qi-tonifying effects of honey-processed Astragalus on spleen qi deficiency rats and predicted the mechanisms by aggregating metabonomics, lipidomics and network pharmacology. The results revealed that body weights, symptom scores, the levels of red blood cell, white blood cell, lymphocyte, spleen and thymus indexes, and three cytokines (TNF-α, IL-6, IFN-γ) in honey-processed Astragalus treated rats were improved in comparison with spleen qi deficiency rats. In parallel, based on the 26 biomarkers screened in metabonomics and lipidomics, we inferred that glycerophospholipid metabolism significantly regulated in pathway analysis was connected with qi-tonifying effects. Moreover, the network pharmacology analysis concluded that the compounds targets of honey-processed Astragalus CDK2, NOS3, MAPK14, PTGS1 and PTGS2 interacted with markers targets PLA2G(s) family and LYPLA1 could be responsible for regulation of glycerophospholipid metabolism to develop qi-tonifying effects. What’s more, the above processes were possibly through VEGF signaling and MAPK signaling pathways.

CAS / MDL: 540-69-2 108-73-6
研究领域: 中医药 · 药理学 · 代谢组学 · 脂质组学 · 网络药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Cellular and Infection Microbiology · 2022 · IF 6.073

Elucidation of the Reinforcing Spleen Effect of Jujube Fruits Based on Metabolomics and Intestinal Flora Analysis

Yi Yan-ling,Li Yao,Guo Sheng,Yan Hui,Ma Xin-fei,Tao Wei-wei,Shang Er-xin,Niu Yang,Qian Da-wei,Duan Jin-ao

Jujube (Ziziphus jujuba Mill.) fruit (JF) is widely consumed as food in Asian countries due to its potential effects for human health. As a traditional Chinese medicine, JF is often used to treat anorexia, fatigue and loose stools caused by spleen deficiency syndromes in China, but the mechanism underlying this effect has not been thoroughly elucidated. In this study, a rat model of spleen deficiency syndromes was adopted to investigate the therapeutic effect of JF extract and its possible mechanism by metabolomics analyses of plasma and urine as well as the intestinal flora analysis. The results showed that the changes in plasma and urine metabolites caused by spleen deficiency were reversed after administration of JF, and these changed endogenous metabolites were mainly involved in retinol metabolism, pentose and glucuronate interconversions, nicotinate and niacinamide metabolism pathways. The 16S rDNA sequencing results showed that JF could regulate intestinal flora imbalance caused by spleen deficiency. The covariance analysis of intestinal flora structure and metabolome indicated that Aerococcus may be a candidate strain for predicting and treating the metabolic pathways of spleen deficiency and related disorders. In summary, it can be revealed that spleen deficiency, which alters metabolic profiles and the intestinal flora, could be alleviated effectively by JF extract.

CAS / MDL: 6763-34-4
研究领域: 药理学 · 中医中药 · 微生物学 · 代谢组学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2022 · IF 5.195

Deep-fried Atractylodes lancea rhizome alleviates spleen deficiency diarrhea–induced short-chain fatty acid metabolic disorder in mice by remodeling the intestinal flora

Chunlian Liu,Chengcheng Song,Yan Wang,Yangxin Xiao,Zhongshi Zhou,Guosheng Cao,Xiongjie Sun,Yanju Liu

Ethnopharmacological relevance Atractylodes lancea (Thunb.) DC. is a Chinese herb that has been commonly used to treat spleen-deficiency diarrhea (SDD) in China for over a thousand years. However, the underlying mechanism of its antidiarrheal activity is not fully understood. Aim of the study The antidiarrheal effects of the ethanol extract of deep-fried A. lancea rhizome (EEDAR) due to spleen deficiency induced by folium sennae (SE) were determined on the regulation of the short-chain fatty acid (SCFA) metabonomics induced by the intestinal flora . Materials and methods The effects of EEDAR on a SE-induced mouse model of SDD were evaluated by monitoring the animal weight, fecal water content, diarrhea-grade rating, goblet cell loss, and pathological changes in the colon. The expression of inflammatory factors (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-6, IL-10), aquaporins (AQP3, AQP4, and AQP8), and tight junction markers (ZO-1, occludin , claudin-1) in colon tissues were determined using quantitative polymerase chain reaction and western blotting . SCFA metabonomics in the feces of mice treated with EEDAR was evaluated using gas chromatography–mass spectrometry. Furthermore, 16S rDNA sequencing was used to determine the effect of EEDAR on the intestinal flora of SDD mice, and fecal microbiota transplantation (FMT) was used to confirm whether the intestinal flora was essential for the anti-SDD effect of EEDAR. Results Treatment with EEDAR significantly improved the symptoms of mice with SDD by inhibiting the loss of colonic cup cells, alleviating colitis , and promoting the expression of AQPs and tight junction markers. More importantly, the effect of EEDAR on the increase of SCFA content in mice with SDD was closely related to the gut microbiota composition. EEDAR intervention did not significantly improve intestinal inflammation or the barrier of germ-free SDD mice, but FMT was effective. Conclusion EEDAR alleviated SE-induced SDD in mice, as well as the induced SCFA disorder by regulating the imbalance of the intestinal microbiota.

研究领域: 药理学 · 微生物学 · 代谢组学 · 胃肠病学 · 民族药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2023 · IF 5.4

A screening strategy for bioactive components of Bu-Zhong-Yi-Qi-Tang regulating spleen-qi deficiency based on “endobiotics-targets-xenobiotics” association network

Liufang Hu,Jiali Chen,Huifang Duan,Zhenyu Zou,Yuan Qiu,Jing Du,Jiaxu Chen,Xinsheng Yao,Hiroaki Kiyohara,Takayuki Nagai,Zhihong Yao

Ethnopharmacological relevance Bu-Zhong-Yi-Qi-Tang is a famous traditional Chinese medicine formula that has been prevalent in China for over 700 years to treat spleen-qi deficiency related diseases, such as gastrointestinal and respiratory disorders . However, the bioactive components responsible for regulating spleen-qi deficiency remain unclear and have puzzled many researchers. Aim of the study The current study focuses on efficacy evaluation of regulating spleen-qi deficiency and screening the bioactive components of Bu-Zhong-Yi-Qi-Tang. Materials and methods The effects of Bu-Zhong-Yi-Qi-Tang were evaluated through blood routine examination, immune organ index, and biochemical analysis. Metabolomics was utilized to analyze the potential endogenous biomarkers (endobiotics) in the plasma, and the prototypes (xenobiotics) of Bu-Zhong-Yi-Qi-Tang in the bio-samples were characterized using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Then, these endobiotics were used as “bait” to predict targets based on network pharmacology and to screen potential bioactive components from the absorbed prototypes in the plasma by constructing an “endobiotics-targets-xenobiotics” association network. Further, the anti-inflammatory activities of representative compounds (calycosin and nobiletin) were validated through poly(I:C)-induced pulmonary inflammation mice model. Results Bu-Zhong-Yi-Qi-Tang exhibited immunomodulatory and anti-inflammatory activities in spleen-qi deficiency rat, as supported by the observation of increased levels of D-xylose and gastrin in serum, an increase in the thymus index and number of lymphocytes in blood, as well as a reduction in the level of IL-6 in bronchoalveolar lavage fluid. Furthermore, plasma metabolomic analysis revealed a total of 36 Bu-Zhong-Yi-Qi-Tang related endobiotics, which were mainly enriched in primary bile acids biosynthesis, the metabolism of linoleic acid , and the metabolism of phenylalanine pathways. Meanwhile, 95 xenobiotics were characterized in plasma, urine, small intestinal contents, and tissues of spleen-qi deficiency rat after Bu-Zhong-Yi-Qi-Tang treatment. Using an integrated association network, six potential bioactive components of Bu-Zhong-Yi-Qi-Tang were screened. Among them, calycosin was found to significantly reduce the levels of IL-6 and TNF-α in the bronchoalveolar lavage fluid, increase the number of lymphocytes, while nobiletin dramatically decreased the levels of CXCL10, TNF-α, GM-CSF, and IL-6. Conclusion Our study proposed an available strategy for screening bioactive components of BYZQT regulating spleen-qi deficiency based on “endobiotics-targets-xenobiotics” association network.

研究领域: 民族药理学 · 药理学 · 中医 · 代谢组学 · 免疫学 · 炎症研究
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2023 · IF 5.4

Effective substances and mechanism of red ginseng on rats with spleen-deficiency syndrome based on the substance and energy metabolism as well as the “brain-gut” axis

Xu Zhang,Xiaotong Wang,Rui Shi,Xiaoku Ran,Xiahong He,Deqiang Dou

Ethnopharmacological relevance Red ginseng (RG), a processed product of ginseng (GS), is a generally used qi -tonifying medicine in Traditional Chinese Medicine (TCM). According to the TCM principle, RG is also generally applied to spleen-deficiency syndrome (SDS) clinically for its warmer property. However, the effective substances and mechanism of RG on SDS have not been well investigated. Aim of the study The aim of this study was to explore the effective substances and their mechanism of RG on SDS. Materials and methods The SDS model was established with a compound factor method involving an irregular diet, excessive fatigue and sennae folium with a bitter-cold property. The medicine of RG was split by multi-mode separation methods and analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The appearance indexes such as body weight, body temperature, swimming endurance, urine output, and water content of fecal were determined. The biochemical indexes such as D-xylose, SP , VIP and AChE in the digestive system, CRH, ACTH, CORT, E, T3, T4, T, E2 and 5-HT in the endocrine system, CS, NCR , IDH1 , COX and Na + -K + -ATPase in the metabolism of substance and energy, cAMP and cGMP in the cyclic nucleotide system were analyzed by Enzyme-linked immunosorbent assay (ELISA) kits and biochemical kits. The serum metabolites were analyzed by UPLC-QTOF/MS. Furthermore, the gut microbiota and short-chain fatty acids (SCFAs) in feces were analyzed by 16S rRNA sequencing and headspace gas chromatography-mass method. Results The pharmacological experiments showed that total saponin fraction (RGTSF), less polar fraction (RGLPF), and polysaccharides faction (RGPSF) significantly modulated the “brain-gut” axis-related indexes (the levels of VIP, AChE, and 5-HT). Besides, RGTSF also significantly modulated the hypothalamic-pituitary-adrenal (HPA) axis-related indexes as well as the substance and energy metabolism-related indexes (the levels of ACTH, CORT, A, Na + -K + -ATPase, COX, NCR and CS). RGPSF also significantly modulated the hypothalamus-pituitary-thyroid (HPT) axis-related indexes (the levels of T3 and T4). Secondly, metabolomics indicated that RGTSF could significantly regulate the abnormal metabolic pathways associated with the development of SDS, which involved steroid hormone biosynthesis, taurine and hypotaurine metabolism, primary bile acid biosynthesis, and amino acid metabolism. Subsequently, the study of gut microbiota indicated that RGLPF could increase the diversities of the gut microbiota and the relative abundance of Firmicutes in rats with SDS, while RGWEF significantly increased the relative abundance of Bacteroidetes . At the genus level, RGLPF could increase the relative abundance of Lactobacillus in rats with SDS and decrease that of Akkermansia . Meanwhile, the water-eluted fraction (RGWEF) showed a stronger regulation in SCFAs. Conclusion It is for the first time that the effective substances of red ginseng on spleen-deficiency syndrome were studied systematically, and the different mechanisms of the RG fractions involved in substance and energy metabolism as well as the “brain-gut” axis were revealed. The present study demonstrated that RGTSF, RGPSF, and RGLPF were the effective substances of red ginseng for ameliorating spleen-deficiency syndrome, indicating that ginsenosides composed of primary and secondary saponins as well as polysaccharides were the main effective substances for red ginseng in ameliorating spleen-deficiency syndrome.

研究领域: 民族药理学 · 中医药学 · 药理学 · 代谢组学 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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