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BMC Complementary Medicine and Therapies · 2020 ·Vol. 20 ·期 1 ·1-10 · IF 0

“Quantity-effect” research strategy for comparison of antioxidant activity and quality of Rehmanniae Radix and Rehmannia Radix Praeparata by on-line HPLC-UV-ABTS assay

Li Hong-Ying,Fang Jiang-Ji,Shen Hua-Dan,Zhang Xue-Qiong,Ding Xiao-Ping,Liu Jun-Feng

Background Quantitation analysis and chromatographic fingerprint of multi-components are frequently used to evaluate quality of herbal medicines but fail to reveal activity of the components. It is necessary to develop a rational approach of chromatography coupled with activity detection for quality assessment of herbal medicines. Methods An on-line HPLC-ultraviolet detection-2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) free radical scavenging (HPLC-UV-ABTS) method was developed to obtain the chromatographic fingerprints and ABTS +• inhibition profiles (active fingerprints) of Rehmanniae Radix (Dihuang) and Rehmannia Radix Praeparata (Shu Dihuang). Eighteen compounds showing ABTS +• inhibition activity were identified by HPLC-fourier-transform mass spectrometry (HPLC-FTMS). Verbascoside was used as a positive control to evaluate the total activities of the samples and the contribution rate of each compound. The similarities of the chromatographic and active fingerprints were estimated by the vectorial angle cosine method. Results The results showed that the HPLC-UV-ABTS method could efficiently detect antioxidant activity of the herbal medicine samples. The antioxidants were different between the two herbs and several new antioxidants were identified in Shu Dihuang. A function equation was generated in terms of the negative peak area (x) and the concentrations of verbascoside (y, μg/mL), y = 2E-07 ×  4 - 8E-05 ×  3  + 0.0079 ×  2  + 0.5755x + 1.4754, R 2  = 1. Iridoid glycosides were identified as main antioxidants and showed their higher contributions to the total activity of the samples. The total contributions of the three main active components in the Dihuang and Shu Dihuang samples to the total activity, such as echinacoside, verbascoside and an unknown compound, were 39.2–58.1% and 55.9–69.4%, respectively. The potencies of the main active components in the Shu Dihuang samples were two to ten times those in the Dihuang samples. Similarity values for S12 in the chromatographic fingerprints and S03, S12 and P03 in the active fingerprints were less than 0.9. The three batches of samples might show their different quality with the other samples. Conclusions The results suggested that the combination of “quantity-effect” research strategy and the HPLC-UV-ABTS analysis method could comprehensively evaluate the active components and quality of Dihuang and Shu Dhuang.

CAS / MDL: 64-18-6
研究领域: 中药学 · 分析化学 · 药理学
✓ 已验证 产品关联 DOI PubMed
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2025 ·Vol. 26 ·期 8 ·3914 · IF 4.9

Rehmanniae Radix Praeparata in Blood Deficiency Syndrome: UPLC-Q-TOF-MS Profiling, Network Pharmacology, and PI3K-AKT Activation

Ruxi Gao,Fanyi Wang,Xiang Liu,Chu Yuan,Guoshun Shan

This study investigated the therapeutic mechanism of Rehmanniae Radix Praeparata (RRP) in treating blood deficiency syndrome (BDS) through integrated chemical analysis and pharmacological validation. UPLC-Q-TOF-MS identified chemical components of Rehmanniae Radix (RR) and RRP, with network pharmacology analysis suggesting AKT1 and NOS3 in the PI3K-AKT pathway as potential therapeutic targets. Pharmacodynamic evaluations using ELISA, hematological analysis, histopathology, and immunohistochemistry demonstrated RRP’s efficacy in improving hematological parameters, energy metabolism, and organ pathology in BDS mice. Experimental validation via RT-qPCR and Western blot confirmed significant upregulation of AKT1 and NOS3 mRNA and protein expression following RRP treatment. The findings indicate that RRP alleviates BDS by activating the PI3K-Akt signaling pathway to modulate AKT1 and NOS3 expression, providing mechanistic insights into its therapeutic actions.

CAS / MDL: 114-83-0
研究领域: 中药学 · 分子生物学 · 网络药理学 · 病理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2024 · IF 4.8

Radix Rehmanniae Praeparata extracts ameliorate hepatic ischemia-reperfusion injury by restoring lipid metabolism in hepatocytes

Ranyi Luo,Yinhao Zhang,Hong Wang,Bing Xu,Jiaorong Qu,Shuwen Duan,Runping Liu,Jia Liu,Shuo Li,Xiaojiaoyang Li

Ethnopharmacological relevance Hepatic ischemia/reperfusion injury (HIRI) is a common occurrence during or after liver surgery, representing a major cause for postoperative complications or increased morbidity and mortality in liver diseases. Rehmanniae Radix Praeparata (RRP) is a traditional Chinese medicine frequently used and has garnered extensive attention for its therapeutic potential treating cardiovascular and hepatic ailments. Recent studies have indicated the possibility of RRP in regulating lipid accumulation and apoptosis in hepatocytes. Aim of the study This study aimed to investigate the specific mechanisms by which RRP may impede the progression of HIRI through the regulation of lipid metabolism. Materials and methods High-performance liquid chromatography (HPLC) was used to identify the major components of RRP water extract. C57BL/6J mice were orally given RRP at doses of 2.5 g/kg, 5 g/kg, and 10 g/kg for a duration of 7 days before undergoing HIRI surgery. Furthermore, we established a lipid-loaded in vitro model by exposing hepatocytes to oleic acid and palmitic acid (OAPA). The anti-HIRI effect of RRP was determined through transcriptomics and various molecular biology experiments. Results After identifying active ingredients in RRP, we observed that RRP exerted lipid-lowering and hepatoprotective effects on HIRI mice and OAPA-treated hepatocytes. RRP activated AMP-activated protein kinase (AMPK) and inhibited mammalian target of rapamycin (mTOR), which further on the one hand, inhibited the cleavage and activation of sterol regulatory element binding protein 2 (SREBP2) by limiting the movement of SREBPs cleavage-activating protein (SCAP)-SREBP2 complex with the help of endoplasmic reticulum lipid raft-associated protein 1 (ERLIN1) and insulin-induced gene 1 (INSIG1), and on the other hand, promoted liver X receptor α (LXRα) nuclear transportation and subsequent cholesterol efflux. Meanwhile, the anti-lipotoxic effect of RRP can be partly reversed by an LXRα inhibitor but largely blocked by the application of compound C, an AMPK inhibitor. Conclusion Our study elucidated that RRP served as a potential AMPK activator to alleviate HIRI by blocking SREBP2 activation and cholesterol synthesis, while also activating LXRα to facilitate cholesterol efflux. These findings shed new light on the potential therapeutic use of RRP for improving HIRI.

CAS / MDL: 57-10-3
研究领域: 药理学 · 肝病学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMISTRY & BIODIVERSITY · 2024 ·Vol. 21 ·期 8 ·e202302059 · IF 2.3

Preparation of Rehmanniae Radix Praeparata Polysaccharide Iron(III) Complex and Evaluation of Its Biological Activity

Si-Mei Liu,Chong-Ying Liu,Zi-Long Chen,Yan Fang,Fang-Zheng Jiao,Li-Hua Zhang,Ting-Ting Zhang,Peng Zhao

This study extracted and purified a polysaccharide from Rehmanniae radix praeparata (RGP) with an average molecular weight. The structural characteristics of RGP and its iron (III) complex, RGP−Fe(III), were examined for their antioxidant properties and potential in treating iron deficiency anemia (IDA). Analysis revealed that RGP comprised Man, Rha, Gal, and Xyl, with a sugar residue skeleton featuring 1→3; 1→2, 3; and 1→2, 3, 4 linkages, among others. RGP−Fe(III) had a molecular weight of 4.39×10 4 Da. Notably, RGP−Fe(III) exhibited superior antioxidant activity compared to RGP alone. In IDA rat models, treatment with RGP−Fe(III) led to increased weight gain, restoration of key blood parameters including hemoglobin, red blood cells, and mean hemoglobin content, elevated serum iron levels, and decreased total iron-binding capacity. Histological examination revealed no observable toxic effects of RGP−Fe(III) on the liver and spleen. These findings suggest the potential of RGP−Fe(III) as a therapeutic agent for managing IDA and highlight its promising antioxidant properties. Graphical

CAS / MDL: 9004-54-0 9048-71-9
研究领域: 中药学 · 生物化学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICAL & PHARMACEUTICAL BULLETIN · 2020 ·Vol. 68 ·期 5 ·428-435 · IF 1.416

Study on the Changes of Chemical Constituents in Different Compatibilities of Ginseng-Prepared Rehmannia Root and Their Effects on Bone Marrow Inhibition after Chemotherapy

Si-qi Wang,Xiao Yang,Yong-gang Zhang,En-bo Cai,Xiao-man Zheng,Yan Zhao,Ge Li,Mei Han,Li-min Yang

Ginseng (G) and Prepared Rehmannia Root (PRR) are commonly used in traditional Chinese medicine for blood supplementation. This study aimed to study G and PRR with different compatibility ratios changes in chemical composition and inhibition of cyclophosphamide-induced myelosuppression. HPLC was used to determine the chemical constituents of 13 ginsenosides, 5-hydroxymethylfurfural (5-HMF) and verbascoside in different proportions of G-PRR. Balb/c mice were injected intraperitoneally with cyclophosphamide (CTX) to induce bone marrow suppression. The effects of different proportions of G-PRR on peripheral blood, bone marrow nucleated cells, thymus and spleen index of myelosuppressed mice were analyzed. The results showed that the compatibility of G and PRR can promote the dissolution of ginsenosides, and the content of conventional ginsenosides decreased, and the content of rare ginsenosides increased. Different proportions of G-PRR increased the number of peripheral blood and bone marrow nucleated cells in cyclophosphamide-induced bone marrow suppression mice (p < 0.01), increased thymus index (p < 0.01), decreased spleen index (p < 0.01). Different proportions of G-PRR can improve the myelosuppression induced by cyclophosphamide in mice, and the combined effect of G-PRR is better than the single decoction of G and PRR. Among them, G-PRR 2 : 3 and G-PRR 1 : 2 were better than the other groups. These results indicate that different proportion of G-PRR can improve bone marrow suppression, and the combined decoction of G-PRR is better than the separate Decoction in improving bone marrow suppression. This improvement may be related to the changes of the substance basis and active ingredients of G-PRR.

CAS / MDL: 67-47-0 61276-17-3
研究领域: 药理学 · 中医药 · 植物化学 · 肿瘤学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2024 · IF 4.8

Radix Rehmanniae Praeparata promoted zebrafish fin regeneration through aryl hydrocarbon receptor-dependent autophagy

Fengyan Chen,Shiming Pu,Li Tian,Huan Zhang,Huixian Zhou,Yijing Yan,Xiaolin Hu,Qiong Wu,Xueping Chen,Shuk Han Cheng,Shisan Xu

Headings ethnopharmacological relevance Rehmanniae Radix Praeparata (RRP), a staple in traditional Chinese medicine, is derived from Rehmannia glutinosa Libosch and is renowned for its wound-healing properties. Despite its clinical prevalence, the molecular mechanisms underlying RRP's wound-healing effects have not been fully elucidated. Aim of the study This research endeavored to delineate the molecular and cellular mechanisms underlying the beneficial effects of RRP on wound healing, utilizing a zebrafish model. Materials and methods Zebrafish larvae at 3 days post-fertilization were amputated at the fin and subsequently treated with RRP. The pro-wound healing and regenerative effects of RRP were evaluated through morphological analysis, assessment of cell proliferation and apoptosis, Additionally, mechanistic insights were gained through a comprehensive approach encompassing network pharmacology analysis, cell tracing, RNA-sequencing, CRISPR/Cas9 gene editing, and pharmacological inhibition. Results Our findings demonstrate that RRP significantly accelerates caudal fin regeneration in zebrafish following injury by suppressing cell apoptosis, promoting cell proliferation, and upregulating the expression of regenerative-related genes. Furthermore, RRP triggers autophagy signals during the regenerative process, which is attenuated by the autophagy inhibitor chloroquine (CQ). Notably, the administration of RRP enhances the expression of ahr1 and ahr2 in the regenerating fin. Genetic knockout of ahr1a , ahr1b , or ahr2 using CRISPR/Cas9, or pharmacological blockade of AHR signals with the antagonist CH-223191, diminishes the regenerative potential of RRP. Remarkably, zebrafish lacking ahr2 completely lose their fin regeneration ability. Additionally, inhibition of AHR signaling suppresses autophagy signaling during fin regeneration. Conclusions This study uncovers that RRP stimulates fin regeneration in zebrafish by inducing AHR signals and, at least partially, activating the autophagy process. These findings provide novel insights into the molecular mechanisms underlying the wound-healing effects of RRP and may pave the way for the development of novel therapeutic strategies.

CAS / MDL: 886-86-2
研究领域: 药理学 · 分子生物学 · 发育生物学 · 中医
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Pharmacology · 2022 · IF 5.988

Comprehensive Metabolomics and Network Pharmacology to Explore the Mechanism of 5-Hydroxymethyl Furfural in the Treatment of Blood Deficiency Syndrome

Zhang Wensen,Cui Na,Su Fazhi,Wang Yangyang,Yang Bingyou,Sun Yanping,Guan Wei,Kuang Haixue,Wang Qiuhong

Radix Rehmanniae (RR, from Radix Rehmanniae (Gaertn.) DC.) is a natural medicine used in traditional Chinese medicine (TCM) since ancient times for the treatment of blood disorders. RR is steamed to get Rehmanniae Radix Praeparata (RP), which has a tonic effect on blood; the content of 5-hydromethylfurfural (5-HMF) increases more than four times after steaming. Studies have shown that 5-HMF has positive pharmacological effects on cardiovascular and hematological disorders. This study aimed to explore and verify the impact of 5-HMF on rats with chemotherapy-induced blood deficiency syndrome (BDS). Rats were given cyclophosphamide (CP) and acetophenhydrazine (APH) to induce BDS, the coefficients of some organs (liver, spleen, and kidney) were measured, and a routine blood test examined the coefficients of several peripheral blood cells. Metabolomics and network pharmacology were combined to find important biomarkers, targets, and pathways. Western blot was used to detect the expression of CYP17A1 and HSD3B1 proteins in the spleen. All these findings suggested that the 5-HMF significantly increased the number of peripheral blood cells and reversed splenomegaly in rats. In addition, 5-HMF upregulated CYP17A1 and HSD3B1 protein expression in splenic tissues. Also, 5-HMF ameliorated chemotherapy-induced BDS in rats, and its therapeutic mechanism might depend on steroid hormone biosynthesis and other pathways. It acts on blood deficiency via multiple targets and pathways, which is unique to Chinese medicine.

CAS / MDL: 67-47-0
研究领域: 药理学 · 中医药 · 代谢组学 · 网络药理学 · 血液学
✓ 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

Kuntai capsule attenuates premature ovarian insufficiency by activating the FOXO3/SIRT5 signaling pathway in mice: A comprehensive study using UHPLC-LTQ-Orbitrap and integrated pharmacology

Leilei Gong,Jinli Hou,Hongjun Yang,Xueyan Zhang,Jingxia Zhao,Lan Wang,Xiaojie Yin,Xin Feng,Chenghong Yin

Ethnopharmacological relevance Classical prescriptions are not only a primary method of clinical treatment in traditional Chinese medicine (TCM) but also represent breakthroughs in the inheritance and development of this field. Kuntai capsule (KTC), a formulation based on a classical prescription, comprises six TCMs: Rehmanniae Radix Praeparata, Coptidis Rhizoma , Paeoniae Radix Alba , Scutellariae Radix , Asini Corii Colla, and Poria . This formulation possesses various beneficial effects, such as nourishing yin and blood, clearing heat and purging fire, and calming the nerves and relieving annoyance. The investigation of the efficacy and mechanism of KTC in regulating anti-aging factors in the treatment of premature ovarian insufficiency (POI) is not only a prominent topic in classical prescription research but also a crucial issue in the treatment of female reproductive aging using TCM. Aim of the study To evaluate the therapeutic effect of KTC on POI and its underlying mechanism. Materials and methods Healthy and specific pathogen-free (SPF) female Kunming mice aged 6–8 weeks were selected. After acclimatization, the mice were randomly divided into a control, model, and high, middle, and low dose groups of KTC (1.6, 0.8, and 0.4 mg/kg, respectively). Except for the control group, the animals in the other groups were administered a single intraperitoneal injection of 120 mg/kg cyclophosphamide and 30 mg/kg Busulfan to induce the model of POI. After modeling, the mice were treated with the corresponding drugs for 7 days. Serum and ovarian tissues were collected, and the levels of serum follicle-stimulating hormone (FSH), estradiol (E2), and superoxide dismutase 2 (SOD2) were determined using enzyme-linked immunosorbent assay (ELISA). The chemical composition of KTC was characterized and analyzed using ultra-high-pressure liquid chromatography-linear ion trap-Orbitrap tandem mass spectrometry. A “drug-component-target-pathway-disease” network was constructed using network pharmacology research methods to identify the key active components of KTC in treating POI and to elucidate its potential mechanism. The protein expression of the FOXO3/SIRT5 pathway was detected by western blotting . Results Compared to the model group, the high-dose group of KTC showed a significant increase in ovarian index, significant increase in levels of E2 and SOD2, and a significant decrease in FSH levels. Through systematic analysis of the chemical constituents of KTC, 69 compounds were identified, including 7 organic acids, 14 alkaloids, 28 flavonoids , 15 terpenoids , 2 lignans , 2 phenylpropanoids, and 1 sugar. Based on network pharmacology research methods, it was determined that KTC exerts its therapeutic effect on POI through multiple components (paeoniflorin and malic acid), multiple targets (FOXO3 and SIRT5), and multiple pathways (prolactin signaling pathway, longevity regulating pathway, and metabolic pathways). The accuracy of the network pharmacology prediction was further validated by detecting the protein expression of SIRT5 and FOXO3a, which showed a significant increase in the middle and high-dose groups of KTC compared to the model group. Conclusions KTC may effectively treat POI through a multi-component, multi-target, multi-pathway approach, providing an experimental basis for using KTC based on classical prescriptions in the treatment of POI.

CAS / MDL: 55-98-1 50-18-0
研究领域: 药理学 · 中医妇科 · 信号传导 · 分析化学 · 整合药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BMC Complementary Medicine and Therapies · 2022 ·Vol. 22 ·期 1 ·1-14 · IF 2.838

Metabolomic strategies and biochemical analysis of the effect of processed Rehmanniae radix extract on a blood-deficient rat model

Wang Yang-yang,Zhou Ning,Shan Zeng-fu,Ke Ying-ying,Liu Zhen,Liu Zhen-hui,Feng Wei-sheng,Zheng Xiao-ke

Background Rehmanniae Radix (RR), an herb with numerous pharmacological effects, is widely used in traditional Chinese medicine for the treatment of blood deficiency syndrome, either alone or in combination with other herbs. However, the mechanism by which processed Rehmanniae Radix (PRR) improves blood enrichment efficacy has not been clearly defined. Methods Ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) and biochemical methods were combined to explore the hematopoietic functional mechanisms of PRR on blood deficiency in a rat model, as well as the potential active ingredient for blood enrichment efficacy. The pharmacological effects of PRR were evaluated on a rat blood deficiency model induced by cyclophosphamide in combination with 1-acetyl-2-phenylhydrazine. The blood routine index, including white blood cell (WBC), red blood cell (RBC), and platelet (PLT) counts, as well as hemoglobin (HGB) level, and the changing metabolite profile based on urine and serum were assessed. Nontargeted metabolomic studies, combined with biochemical analyses, were employed to clarify pharmacological mechanisms. Results PRR significantly increased the blood routine index levels and reversed the levels of SOD, GSH, and ATP. The PRR group was similar to the control group, as determined from the metabolic profile. All of the 60 biomarkers, representing the typical metabolic characteristics of the blood-deficient rat model, mainly involved energy metabolism dysfunction, the peripheral circulation system, and oxidative damage in the body. This improvement may be attributed to changes in polysaccharide and sixteen non-polysaccharide compounds in PRR, which were caused by processing RR with rice wine. Conclusions The strategies of integrated metabolomic and biochemical analyses were combined, revealing the biological function and effective mechanism of PRR.

CAS / MDL: 114-83-0
研究领域: 药理学 · 中药学 · 代谢组学 · 生物化学 · 动物模型研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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