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1.
Rapid Commun Mass Spectrom ; 38(20): e9893, 2024 Oct 30.
Article in English | MEDLINE | ID: mdl-39185578

ABSTRACT

RATIONALE: Anemarrhenae Rhizoma (AR) has been a frequently utilized traditional Chinese medicine (TCM) for an extended period, with its salt-processed variant being a prevalent application form. Contemporary pharmacological investigations have demonstrated that the salt-processed iteration exhibits a multitude of markedly augmented pharmacological properties. However, whether the pharmacodynamic material basis of this change is related to volatile substances remains unclear. The aim of this study was to develop a strategy to screen volatile pharmacodynamic substances in AR and salt-processed AR (SAR). METHODS: A comprehensive approach was developed to identify volatile pharmacodynamic compounds by integrating plant metabolomics, target network pharmacology, and molecular docking technology. Plant metabolomics using GC-MS analysis was conducted to identify volatile chemical markers distinguishing between AR and SAR. Subsequently, network pharmacology was utilized to investigate the correlation between chemical markers and associated diseases. Following this, molecular docking technology was utilized to explore the correlation between chemical markers and disease targets, resulting in the discovery of potential quality control markers. RESULTS: Fifty volatile compounds were isolated and identified in the salt of AR and SAR. The findings from plant metabolomics analysis demonstrated a distinct differentiation, revealing 13 volatile chemical markers that distinguish between AR and SAR. A target (PPARG) associated with diabetes was identified through target network pharmacology analysis. Thirteen volatile components were subsequently chosen as potential quality markers, taking into account their hypoglycemic activity. CONCLUSIONS: The method developed provides a novel strategy for the identification of pharmacophores in AR and SAR, as well as establishing a foundation for the exploration of the volatile differential components and pharmacodynamics in various processed products of TCMs. Additionally, the findings of this study can serve as a theoretical framework for the development and utilization of volatile components in AR and its processed derivatives.


Subject(s)
Anemarrhena , Drugs, Chinese Herbal , Gas Chromatography-Mass Spectrometry , Metabolomics , Molecular Docking Simulation , Rhizome , Volatile Organic Compounds , Gas Chromatography-Mass Spectrometry/methods , Metabolomics/methods , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/analysis , Volatile Organic Compounds/chemistry , Volatile Organic Compounds/analysis , Volatile Organic Compounds/metabolism , Rhizome/chemistry , Anemarrhena/chemistry , Network Pharmacology
2.
J Ethnopharmacol ; 334: 118539, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-38986754

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Anemarrhena asphodeloides Bunge (Ane) and Phellodendron chinense C. K. Schneid (Phe) is classical herb pair in traditional Chinese medicine, commonly used to ameliorate the symptoms of Benign Prostatic Hyperplasia (BPH). However, the mechanisms underlying this effect are remained indistinct. AIM OF THE STUDY: This study aimed to clarify potential therapeutic mechanisms of herb pair on BPH from a metabolic perspective. MATERIALS AND METHODS: Testosterone propionate-induced BPH rat model was established, prostatic parameters, histopathology and the levels of serum dihydrotestosterone (DHT) and testosterone (T) were used to evaluate the pharmacological effect of the herb pair on BPH. Subsequently, untargeted metabolomics of prostate tissues samples was performed by UHPLC-Q-Exactive-Orbitrap-MS, followed by multivariate statistical analysis. Targeted metabolomics by UHPLC-QQQ-MS was further utilized to verify and supplement the results of lipids and amino acids found by untargeted metabolomics, clarifying the relationship between disease, herbal pair and metabolism pathway. RESULTS: The study found that Ane-Phe could relieve the progression of BPH and regulate metabolic imbalances. The levels of 13 metabolites decreased and 11 increased in prostatic tissues including glycerolphospholipid, arachidonic acid, citric acid and so on, these altered metabolites were primarily associated with TCA cycle, arachidonic acid metabolism, lipid metabolism and amino acid metabolism. Furthermore, targeted metabolomics was fulfilled to further analyze the lipid metabolism disorders, the levels of 5 lipids in serum and 21 in prostatic tissues were changed in the herb pair group compared to the model group, which closely related to glycerophospholipid, sphingolipid and glycerolipid metabolism. Besides, amino acid metabolism may be regulated by activating arginine metabolism pathway. CONCLUSIONS: In this study, the combination of untargeted metabolomics and targeted metabolomics was applied to explore therapeutic mechanisms of Ane-Phe on BPH. In summary, Ane-Phe could improve the levels of endogenous metabolites by regulating multiple metabolic pathways and plays a role in energy supply, anti-inflammation and oxidative stress in BPH treatment.


Subject(s)
Anemarrhena , Metabolomics , Phellodendron , Prostatic Hyperplasia , Rats, Sprague-Dawley , Male , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/metabolism , Prostatic Hyperplasia/pathology , Animals , Phellodendron/chemistry , Anemarrhena/chemistry , Rats , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Prostate/drug effects , Prostate/metabolism , Prostate/pathology , Disease Models, Animal , Chromatography, High Pressure Liquid
3.
J Pharm Biomed Anal ; 248: 116264, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38889577

ABSTRACT

Anemarrhena asphodeloides Bunge-Phellodendron chinense Schneid (AAPC) is one of the most widely accepted herb pairs in Chinese medicine prescription for treating benign prostatic hyperplasia (BPH). However, the mechanisms underlying the combination of the two herbs for anti-BPH are still not completely clear. To uncover the potential mechanism of the AAPC herb pair in the treatment of BPH, chemical profiling, network pharmacology, serum metabonomics and experimental validation were integrated. UHPLC-Q-Exactive Orbitrap-MS was performed to characterize the chemical profiling of the herb pair extract, and network pharmacology was employed to forecast the potential effective components, core targets and key signaling pathways. Then, western blot and RT-PCR experiments were conducted to verify the PI3K/Akt/NF-κB signaling pathway predicted by network pharmacology. Finally, the serum differential metabolites and metabolic pathways were analyzed by serum non-targeted metabonomics, and these results were jointly analyzed by MetScape. 51 chemical components of the AAPC herb pair extract were identified, including phellodendrine, magnoflorine, berberine, mangiferin, anemarsaponin BIII, etc. In network pharmacology, the predicted core targets of these components include AKT1, TNF, EGFR, PTGS2, PIK3CA, etc. The KEGG pathway enrichment analysis indicated that PI3K-Akt, Rap1 and MAPK signaling pathways may play a key role in the AAPC herb pair for the treatment of BPH, and the results of animal experiments demonstrated that the herb pair could significantly inhibit the activation and expression of p-PI3K/PI3K, p-Akt/Akt, p-NF-κB/NF-κB in protein and mRNA levels. Furthermore, 31 serum differential metabolites and three main metabolic pathways were obtained by serum non-targeted metabonomics. And the crucial metabolic pathway of arachidonic acid (AA) was obtained by integrated analysis of network pharmacology and metabonomics results. In conclusion, the AAPC herb pair can improve BPH through inhibiting the activation and expression of the PI3K/Akt/NF-κB signaling pathway and AA metabolism.


Subject(s)
Anemarrhena , Drugs, Chinese Herbal , Metabolomics , Network Pharmacology , Phellodendron , Prostatic Hyperplasia , Signal Transduction , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/blood , Male , Anemarrhena/chemistry , Metabolomics/methods , Network Pharmacology/methods , Phellodendron/chemistry , Animals , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Signal Transduction/drug effects , Chromatography, High Pressure Liquid/methods , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley , NF-kappa B/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Plant Extracts/pharmacology
4.
Zhongguo Zhong Yao Za Zhi ; 49(1): 88-99, 2024 Jan.
Article in Chinese | MEDLINE | ID: mdl-38403342

ABSTRACT

Anemarrhena asphodeloides is a common medicinal material used in clinical prescriptions and Chinese patent medicine. In this study, the Illumina platform was used to obtain the chloroplast genome sequences of seven kinds of A. asphodeloides from different areas. The specific DNA barcodes were screened by comparative genomics analysis, and the DNA barcodes were used to identify the germplasm resources and analyze the genetic diversity of A. asphodeloides samples from different areas in China. All the seven chloroplast genomes had a ring structure. The total length was 156 801-156 930 bp, and 113 genes were annotated, including 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. The comparative genomics analysis showed that rps16, trnG-GCC, atpF, rpoB, ycf3, rpl16, ndhF, trnS-GCU_trnG-GCC, petN-psbM, and ndhF-rpl32 were potential candidates for specific DNA barcodes of A. asphodeloides. In this study, the second intron of ycf3 and atpF intron sequences with a sequence length of 700-800 bp and easy amplification were selected for polymerase chain reaction(PCR) amplification and sequencing of 594 samples from 26 areas. The sequence analysis showed that six and eight haplotypes of ycf3 and atpF sequences could be identified, respectively, and 17 haplotypes could be identified by combined analysis of the two sequences, which were named Hap1-Hap17. The haplotype diversity(H_d), nucleotide diversity(P_i), and genetic distance of A. asphodeloides in 26 populations were 0.68, 0.93×10~(-3), and 0-0.003 1, respectively, indicating that the genetic diversity within the species of A. asphodeloides is rich. The intermediary adjacent network analysis showed that Hap5 was the oldest haplotype, which was mainly distributed in Yixian county of Baoding, Hebei province, Hequ county of Xinzhou, Shanxi province, and Xiangfen county of Linfen, Shanxi province. This study has important guiding significance for the identification of A. asphodeloides species, the protection and development of germplasm resources, and the identification of production areas, and it provides a research basis for further revealing the genetic evolution law of A. asphodeloides.


Subject(s)
Anemarrhena , Anemarrhena/chemistry , DNA Barcoding, Taxonomic , Genetic Variation , China , Phylogeny
5.
J Ethnopharmacol ; 319(Pt 3): 117250, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-37832811

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Based on the theory of traditional Chinese medicine (TCM), diabetic cardiomyopathy (DCM) belongs to the category of "Xiaoke disease" according to the symptoms, and "stasis-heat" is the main pathogenesis of DCM. The Chinese medicine Anemarrhena asphodeloides Bunge (AAB), as a representative of heat-clearing and engendering fluid, is often used clinically in the treatment of DCM. Anemarrhena asphodeloides Bunge total saponins (RATS) are the main bioactive components of AAB, the modern pharmacologic effects of RATS are anti-inflammatory, hypoglycemic, and cardioprotective. However, the potential protective mechanisms of RATS against DCM remain largely undiscovered. AIM OF THE STUDY: The primary goal of this study was to explore the effect of RATS on DCM and its mechanism of action. MATERIALS AND METHODS: Streptozotocin and a high-fat diet were used to induce DCM in rats. UHPLC/Q-TOF-MS was used to determine the chemical components of RATS. The degenerative alterations and apoptotic cells in the heart were assessed by HE staining and TUNEL. Network pharmacology was used to anticipate the probable targets and important pathways of RATS. The alterations in metabolites and main metabolic pathways in heart tissue were discovered using 1 H-NMR metabolomics. Ultimately, immunohistochemistry was used to find critical pathway protein expression. RESULTS: First of all, UHPLC/Q-TOF-MS analysis showed that RATS contained 11 active ingredients. In animal experiments, we found that RATS lowered blood glucose and lipid levels in DCM rats, and alleviated cardiac pathological damage, and decreased cardiomyocyte apoptosis. Furthermore, the study found that RATS effectively reduced inflammatory factor release and the level of oxidative stress. Mechanistically, RATS downregulated the expression levels of PI3K, AKT, HIF-1α, LDHA, and GLUT4 proteins. Additionally, glycolysis was discovered to be a crucial pathway for RATS in the therapy of DCM. CONCLUSIONS: Our findings suggest that the protective effect of RATS on DCM may be attributed to the inhibition of the PI3K/AKT/HIF-1α pathway and the correction of glycolytic metabolism.


Subject(s)
Anemarrhena , Diabetes Mellitus , Diabetic Cardiomyopathies , Saponins , Animals , Diabetic Cardiomyopathies/drug therapy , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Anemarrhena/chemistry , Saponins/pharmacology , Saponins/therapeutic use , Saponins/chemistry , Glycolysis
6.
Int J Biol Macromol ; 249: 126017, 2023 Sep 30.
Article in English | MEDLINE | ID: mdl-37517752

ABSTRACT

Anemarrhena asphodeloides polysaccharide (AAP70-1) was reported to have immunomodulatory effects in our previous report. To further improve the immunomodulatory effects of AAP70-1, an A. asphodeloides polysaccharide-zinc complex (AAP-Zn) was synthesized using a ZnCl2 modification method, and the potential mechanisms by which AAP-Zn activates macrophages were investigated. The results showed that the structural features of AAP-Zn were similar to those of AAP70-1 with a Zn content of 0.2 %, confirming that Zn mainly interacted with AAP70-1 by forming ZnO coordination bonds and Zn…OH bonds. In addition, the administration of AAP70-1 and AAP-Zn effectively improved the immunomodulatory effects by enhancing phagocytosis and upregulating the mRNA expression of cytokines (TNF-α, IL-6, IL-1ß, and IL-18), as well as increasing the production levels of nitric oxide (NO) and reactive oxygen species (ROS) in zebrafish embryos. The intracellular mechanism by which AAP-Zn activates macrophages was found to involve activation of the NF-κB and MAPK signaling pathways. Our findings suggested that AAP-Zn may be a potential immunopotentiator in the field of biomedicine or functional foods.


Subject(s)
Anemarrhena , NF-kappa B , Animals , NF-kappa B/metabolism , Anemarrhena/chemistry , Zinc/pharmacology , Zebrafish/metabolism , Polysaccharides/pharmacology , MAP Kinase Signaling System
7.
Int J Biol Macromol ; 236: 123843, 2023 May 01.
Article in English | MEDLINE | ID: mdl-36858093

ABSTRACT

In this study, an acid polysaccharide (AABP-1B) was extracted from the rhizome of Anemarrhena asphodeloides Bunge and purified using 60 % alcohol precipitation and DEAE-52 cellulose. The molecular weight of AABP-1B was 105 kDa, and it consisted of mannose (Man), rhamnose (Rha), galacturonic acid (GalA), glucose (Glc), galactose (Gal), and arabinose (Ara) in a ratio of 6.3:1.3:1.1:0.2:0.4:0.7. Methylation and NMR analyses revealed that the backbone of AABP-1 consists of 4)-ß-D-Manp-(1 and 4)-2-O-acetyl-ß-D-Manp-(1. In addition, the biological activity assays showed that AABP-1B not only displays potential antioxidant activity but also exhibits the α-glucosidase and α-amylase inhibitory effect. Moreover, AABP-1B enhanced glucose consumption and glycogen synthesis in insulin-resistant (IR) HepG2 cells. These results suggest that AABP-1B has potential hypoglycemic activity.


Subject(s)
Anemarrhena , Hypoglycemic Agents , Humans , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Antioxidants/pharmacology , Anemarrhena/chemistry , Polysaccharides/pharmacology , Polysaccharides/chemistry , Glucose
8.
Int J Biol Macromol ; 231: 123324, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36657544

ABSTRACT

To discover the polysaccharide with anti-diabetic osteoporosis (DOP) activity and clarify its structure, an arabinomannan (PAAP-1B) with a molecular weight of 14.0 kDa was isolated from Anemarrhena asphodeloides Bge. using column chromatography. It consists of arabinose, mannose, and galactose in a molar ratio of 6:3:1. PAAP-1B has a backbone composed of 1,5-α-Araf, 1,4-ß-Manp, and 1,6-ß-Galp residues that are branched at C3 of α-Araf and ß-Galp residues. The side chains are T-α-Araf, T-α-Manp, T-ß-Galp, and 1,6-ß-Galp. PAAP-1B attenuated DOP and reduced ferroptosis in the femurs and tibias of alloxan-induced mice. It also suppressed ferroptosis in advanced glycation end product-induced osteoblasts by decreasing 4-hydroxynonenal, malondialdehyde, mitochondrial reactive oxidative species levels, and lipid peroxidation, while reversing the downregulation of solute carrier family 7 membrane 11 and glutathione expression.


Subject(s)
Anemarrhena , Mice , Animals , Anemarrhena/chemistry , Polysaccharides/chemistry , Mannans , Galactose
9.
Rapid Commun Mass Spectrom ; 37(7): e9473, 2023 Apr 15.
Article in English | MEDLINE | ID: mdl-36645740

ABSTRACT

RATIONALE: Anemarrhenae Rhizoma (AR) has been an often used traditional Chinese medicine (TCM) for a long time. Its salt-processed form is one of the most common application forms. Modern pharmacological research has shown that the salt-processed product has various significantly enhanced pharmacological activities. However, the pharmacodynamic material basis of this change is not yet known. The aim of this study was to develop a strategy to screen pharmacodynamic substances in AR and salt-processed AR (SAR). METHODS: An integrated strategy combining plant metabolomics with molecular docking technology was established to screen pharmacodynamic substances. The plant metabolomics analysis was performed to select the chemical markers between AR and SAR. Then, molecular docking technology was applied to explore the relationship between chemical markers and diabetes targets (α-glucosidase). Finally, potential quality control markers were screened. RESULTS: There were significant differences in the quantification of nine steroidal saponins between AR and SAR. The results of plant metabolomics analysis showed a quite clear discrimination including 29 chemical markers between AR and SAR. Taking the hypoglycemic activity into consideration, 16 steroidal saponins were selected as potential quality markers. CONCLUSIONS: The developed method not only supplied an optional solution to search for pharmacophores in AR and SAR, but also provided a foundation for the study of the differential components and pharmacodynamics in various processed products of TCMs.


Subject(s)
Anemarrhena , Drugs, Chinese Herbal , Saponins , Drugs, Chinese Herbal/chemistry , Molecular Docking Simulation , Anemarrhena/chemistry , Quality Control , Saponins/analysis , Metabolomics
10.
Phytother Res ; 37(5): 1951-1967, 2023 May.
Article in English | MEDLINE | ID: mdl-36631974

ABSTRACT

Increased glycolytic in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) not only contributes to early-stage disease pathogenesis but leads to sustained proliferation of FLS. Given the importance of PKM2 in glycolysis and apoptosis, PKM2 is considered a potential therapeutic and drug discovery target in RA. Total saponins of anemarrhena (TSA), a class of steroid saponins, originated from Anemarrhena asphodeloides Bge. In this study, we verified that 200 mg/kg TSA could significantly alleviate inflammation and the pathological characteristics of RA and inhibit synovial hyperplasia in AA rats. We confirmed that sarsasapogenin (SA) was the principal active ingredient absorbed into the blood of TSA by the UPLC/Q Exactive MS test. Then we used TNF-α-induced MH7A to get the conclusion that 20 µM SA could effectively inhibit the glycolysis by inhibiting the activity of PKM2 tetramer and glucose uptake. Moreover, 20 µM SA could suppress proliferation, migration, invasion, and cytokine release of FLS, interfere with the growth cycle of FLS, and induce FLS apoptosis by depressing the phosphorylation of PKM2. At last, In-1, a potent inhibitor of the PKM2 was used to reverse verify the above results. Taken together, the key mechanisms of SA on RA treatment through downregulating the activity of PKM2 tetramer and phosphorylation of PKM2 inhibited pathological glycolysis and induced apoptosis to exert inhibition on the proliferation and invasion of RA FLS.


Subject(s)
Anemarrhena , Arthritis, Rheumatoid , Synoviocytes , Animals , Rats , Anemarrhena/chemistry , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/pathology , Cell Proliferation , Cells, Cultured , Fibroblasts , Glycolysis , Synovial Membrane , Saponins/pharmacology
11.
Molecules ; 27(6)2022 Mar 21.
Article in English | MEDLINE | ID: mdl-35335393

ABSTRACT

Sarsasapogenin is a natural steroidal sapogenin molecule obtained mainly from Anemarrhena asphodeloides Bunge. Among the various phytosteroids present, sarsasapogenin has emerged as a promising molecule due to the fact of its diverse pharmacological activities. In this review, the chemistry, biosynthesis and pharmacological potentials of sarsasapogenin are summarised. Between 1996 and the present, the relevant literature regarding sarsasapogenin was obtained from scientific databases including PubMed, ScienceDirect, Scopus, and Google Scholar. Overall, sarsasapogenin is a potent molecule with anti-inflammatory, anticancer, antidiabetic, anti-osteoclastogenic and neuroprotective activities. It is also a potential molecule in the treatment for precocious puberty. This review also discusses the metabolism, pharmacokinetics and possible structural modifications as well as obstacles and opportunities for sarsasapogenin to become a drug molecule in the near future. More comprehensive preclinical studies, clinical trials, drug delivery, formulations of effective doses in pharmacokinetics studies, evaluation of adverse effects and potential synergistic effects with other drugs need to be thoroughly investigated to make sarsasapogenin a potential molecule for future drug development.


Subject(s)
Anemarrhena , Spirostans , Anemarrhena/chemistry , Drug Design , Spirostans/chemistry , Spirostans/pharmacology
12.
Food Funct ; 13(4): 1797-1807, 2022 Feb 21.
Article in English | MEDLINE | ID: mdl-35083996

ABSTRACT

A new polysaccharide (AABP-2B) was obtained from Anemarrhena asphodeloides Bunge after purification by gradient alcohol precipitation and DEAE-52 cellulose column chromatography. AABP-2B was confirmed to be a homogeneous polysaccharide with a molecular weight of 5800 Da and was composed of mannose and glucose at a molar ratio of 7.2 : 2.8. Structural analysis demonstrated that the backbone of AABP-2B was mainly composed of 4)-ß-D-Manp-(1, 4,6)-ß-D-Glcp-(1 and 3,6)-ß-D-Manp-(1. The hypoglycaemic effect of AABP-2B was evaluated by its inhibition of α-glucosidase activities and insulin resistance in a HepG2 cell model. The results showed that AABP-2B displayed α-glucosidase inhibitory activities and could significantly improve glucose consumption by activating the IRS-1/PI3K/Akt signalling pathway in insulin-resistant HepG2 cells. Hence, AABP-2B may have potential as a functional food or medicine for diabetes therapy.


Subject(s)
Anemarrhena/chemistry , Glycoside Hydrolase Inhibitors , Insulin Resistance/physiology , Mannans , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Hep G2 Cells , Humans , Mannans/chemistry , Mannans/pharmacology , Signal Transduction/drug effects
13.
Bioorg Chem ; 119: 105546, 2022 02.
Article in English | MEDLINE | ID: mdl-34954573

ABSTRACT

Pulmonary fibrosis is a progressive interstitial lung disease with poor prognosis. Anemarrhenae Rhizoma is a traditional Chinese herbal medicine and has been applied in clinical practice for a long history. Recently, components of Anemarrhenae Rhizoma were reported to possess anti-inflammatory and immunomodulatory features; however, the effect of them on pulmonary fibrosis remains unknown. In this study, we explored the therapeutic effect of total extract of Anemarrhenae Rhizoma (TEAR) on bleomycin-induced pulmonary fibrosis. Pulmonary fibrosis rat model was established by a single intratracheal instillation of bleomycin, three doses of TEAR were intragastrically administered for consecutive 28 days. Subsequent to sacrificing of rats, pulmonary fibrosis was observed in rats treated with bleomycin, but administration of TEAR attenuated lung fibrosis, as evidenced by the improved lung histopathological damage and decreased weight loss and lung index. Moreover, TEAR treatment inhibited the inflammatory response in lung fibrosis, which was shown by the reduced nitrogen oxide level and myeloperoxidase activity. Furthermore, TEAR modulated the redox balance in lung tissue by alleviated lipid peroxidation and enhanced enzymatic antioxidants activity. Meanwhile, TEAR protected the rats from fibrosis in a dose-dependent manner, and the anti-fibrotic activity of TEAR may be related to the modulation of TGF-ß1/Smad signaling pathway. Collectively, TEAR alleviates bleomycin-induced pulmonary fibrosis, indicating perspectives for development of a potential agent for lung fibrosis therapy.


Subject(s)
Anemarrhena/chemistry , Drugs, Chinese Herbal/therapeutic use , Flavonoids/therapeutic use , Pulmonary Fibrosis/drug therapy , Rhizome/chemistry , Saponins/therapeutic use , Animals , Bleomycin , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/isolation & purification , Flavonoids/chemistry , Flavonoids/isolation & purification , Male , Medicine, Chinese Traditional , Molecular Structure , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/pathology , Rats , Rats, Sprague-Dawley , Saponins/chemistry , Saponins/isolation & purification , Structure-Activity Relationship
14.
J Ethnopharmacol ; 284: 114740, 2022 Feb 10.
Article in English | MEDLINE | ID: mdl-34737006

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Flavonoids are the main components of the traditional Chinese medicine Anemarrhenae Rhizoma (dried rhizome of Anemarrhena asphodeloides Bge.), which has been reported to possess activity against inflammation and tumor. AIM OF STUDY: Regulation of the arachidonic acid (AA) cascade through cyclooxygenase (COX) and lipoxygenase (LOX) represent the two major pathways to treat inflammatory of benign prostatic hyperplasia (BPH). In this study, Anemarrhenae Rhizoma flavonoids and its main compounds (mangiferin, neomangiferin and isomangiferin) were investigated for effects on AA metabolism. METHODS: Ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was used to monitor AA metabolites in BPH rats and in PC-3 cells. COX-2 and 5-LOX protein and mRNA levels were measured by Western blot and qPCR, respectively, along with histopathological assessment of prostate tissues. RESULTS: Treatment with flavonoids significantly ameliorated BPH-associated prostate inflammation and inhibited the expression of COX-2 and 5-LOX at the protein and mRNA levels. Quantitative metabolomic analysis of blood plasma showed flavonoids treatment decreased AA levels and its metabolites associated with the COX and LOX pathways. Further exploration of the flavonoid compounds mangiferin, neomangiferin and isomangiferin showed they inhibited AA metabolism to varying degrees in PC-3 cell cultures. CONCLUSION: Anemarrhenae Rhizoma flavonoids act to inhibit BPH-related inflammation in vivo and in vitro by targeting AA metabolism and interfering with COX and LOX pathways. The identification of mangiferin, neomangiferin and isomangiferin as anti-inflammatory components suggests flavonoids interventions represent a promising therapeutic approach for BPH.


Subject(s)
Anemarrhena/chemistry , Flavonoids/pharmacology , Inflammation/drug therapy , Prostatic Hyperplasia/drug therapy , Animals , Arachidonate 5-Lipoxygenase/genetics , Chromatography, High Pressure Liquid , Cyclooxygenase 2/genetics , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Flavonoids/isolation & purification , Humans , Male , Metabolomics , PC-3 Cells , Rats , Rats, Sprague-Dawley , Rhizome , Tandem Mass Spectrometry
15.
Eur J Pharmacol ; 909: 174377, 2021 Oct 15.
Article in English | MEDLINE | ID: mdl-34302815

ABSTRACT

Anemarrhena asphodeloides originated from the rhizome of Liliaceae Anemarrhena asphodeloides. One of the active pharmacological components of Anemarrhena asphodeloides is timosaponin (TSA), which reduces blood lipids and shows antioxidation and anti-inflammatory effects, but its mechanism is unclear. The objective of this study was to investigate the effect of TSA on oxidative stress induced by a long-term high-fat diet in obese rats. Body weight and the obesity index of the rats were measured during the experiment. Total antioxidant capacity (T-AOC), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were used to detect oxidative stress indexes in serum and liver tissue. To observe the effect of TSA on the liver and adipose tissue of rats with oxidative stress, hematoxylin & eosin (H&E) staining was used. The p-NF-κB, NAD(P)H: quinone oxidoreductase 1 (NQO-1), Heme oxygenase 1 (HO-1), and Nrf2 in Nrf2/HO-1 and NF-κB pathways were assayed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. TSA was found to improve oxidative stress in obese rats by reducing MDA levels and increasing T-AOC and GSH-Px levels. Histological examination revealed that TSA effectively attenuated liver damage and improved obesity in rats. TSA was found to down-regulate the protein level of p-NF-κB and up-regulate the protein level of Nrf2/HO-1. These results suggested that TSA could effectively block inflammation and dyslipidemia in obese rats, thus improving oxidative stress, and its mechanism could be related to the Nrf2/HO-1 and NF-κB pathways.


Subject(s)
Anemarrhena/chemistry , Obesity/drug therapy , Saponins/pharmacology , Animals , Diet, High-Fat/adverse effects , Disease Models, Animal , Heme Oxygenase (Decyclizing)/metabolism , Humans , Male , NF-E2-Related Factor 2/agonists , NF-E2-Related Factor 2/metabolism , NF-kappa B/antagonists & inhibitors , NF-kappa B/metabolism , Obesity/etiology , Oxidative Stress/drug effects , Rats , Saponins/therapeutic use , Signal Transduction/drug effects
16.
J Ethnopharmacol ; 277: 114251, 2021 Sep 15.
Article in English | MEDLINE | ID: mdl-34052350

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Anemarrhena asphodeloides is the dry rhizome of Anemarrhena asphodeloides Bge. Anemarrhena Saponins isolated from Anemarrhena asphodeloides are one of the pharmacologically active components of this plant and have blood lipid reduction and blood glucose reduction properties. These facts suggest that these saponins might be helpful in the treatment of insulin resistance. AIM OF THE STUDY: To determine the therapeutic effect of anemarrhena saponins on insulin resistance and the probable underlying mechanism. MATERIALS AND METHODS: Insulin-resistant rats were used as the experimental subject, to observe the therapeutic effect of anemarrhena saponins. The blood glucose and blood lipid parameters were determined using the relevant kits. We used hematoxylin and eosin (H&E) staining to observe the protective effect of anemarrhena saponins on the livers of insulin-resistant rats and reverser transcripition polymerase chain reaction (RT-PCR) to analyze the mRNA expressions patterns of genes related to glucose metabolism and inflammatory factors. The toxicity of anemarrhena saponins to HepG2 cells was calculated using the MTT assay. Further, we conducted in vivo and in vitro experiments, and Western-blot analysis to study the effects of anemarrhena saponins on the IRS-1/PI3K/AKT pathway. RESULTS: Anemarrhena saponins were found to improve dyslipidemia, reduce obesity and inflammation, and alleviate liver injury in insulin-resistant rats. Anemarrhena saponins also reduced the mRNA expression of gluconeogenesis-related genes sunch as G6pase, PEPCK, and GSK3ß in the liver. Moreover, anemarrhena saponins up-regulated the phosphorylation levels of IRS-1, PI3K and AKT, promoted insulin signal transduction, and reduced liver injury induced by insulin resistance. CONCLUSIONS: These findings suggest that anemarrhena saponins could promote insulin signal transduction through the IRS-1/PI3K/AKT pathway, thereby reducing the damage caused by insulin resistance.


Subject(s)
Anemarrhena/chemistry , Insulin Resistance , Obesity/drug therapy , Saponins/pharmacology , Animals , Blood Glucose/drug effects , Diet, High-Fat/adverse effects , Dyslipidemias/drug therapy , Hep G2 Cells , Humans , Inflammation/drug therapy , Insulin/metabolism , Insulin Receptor Substrate Proteins/metabolism , Lipids/blood , Liver/drug effects , Liver/pathology , Male , Obesity/complications , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley , Saponins/isolation & purification
17.
Int J Biol Macromol ; 179: 475-484, 2021 May 15.
Article in English | MEDLINE | ID: mdl-33675837

ABSTRACT

Many Chinese herbs are well known for their neuroprotective and anti-oxidant properties. Extracts of Salvia miltiorrhiza and Anemarrhenae asphodeloides, tanshinone IIA (tanIIA), salvianolic acid B (Sal B) and sarsasapogenin (ML-1), were selected to study their dissociation potential towards Aß42 peptide fibrils and neuroprotective effect on cells. Moreover, derivatives of sarsasapogenin (ML-2, ML-3 and ML-4) have been prepared by the addition of modified carbamate moiety. TanIIA and Sal B have shown to possess a strong ability to dissociate Aß42 fibrils. The dissociation potential of ML-1 increased upon the introduction of carbamate moiety with N-heterocycles. In silico data revealed that derivatives ML-4 and Sal B interact with Aß42 regions responsible for fibril stabilization through hydrogen bonds. Contrary, tanIIA binds close to a central hydrophobic region, which may lead to destabilization of fibrils. Sarsasapogenin derivative ML-2 decreased nitride oxide production, and derivative ML-4 enhanced the growth of neurites. The reported data highlight the possibility of using active compounds to design novel treatment agents for Alzheimer's disease.


Subject(s)
Abietanes/pharmacology , Amyloid beta-Peptides/metabolism , Benzofurans/pharmacology , Neuroprotective Agents/pharmacology , Peptide Fragments/metabolism , Spirostans/pharmacology , Alzheimer Disease/drug therapy , Anemarrhena/chemistry , Cell Line , China , Humans , Plant Extracts , Salvia miltiorrhiza/chemistry
18.
Int J Biol Macromol ; 172: 550-559, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33465362

ABSTRACT

The crude polysaccharide was extracted from A. asphodeloides rhizomes and further purified to produce two fractions F1 (50.0%) and F2 (19.6%). The chemical constitutions of the polysaccharides were neutral sugars (51.4%-89.7%), uronic acids (1.0%-30.2%) and sulfate esters (3.4%-8.1%), with various ratios of monosaccharides including rhamnose (1.4%-6.1%), arabinose (7.1%-21.2%), xylose (0.2%-4.8%), mannose (39.9%-79.0%), glucose (6.0%-11.1%) and galactose (2.6%-22.0%). The molecular properties of the polysaccharides were investigated by the HPSEC-UV-MALLS-RI system, revealing the Mw 130.0 × 103-576.5 × 103 g/moL, Rg 87.6-382.6 nm and SVg 0.3-54.3 cm3/g. The polysaccharides stimulated RAW264.7 cells to produce considerable amounts of NO and up-regulate the expression of TNF-α, IL-1 and COX-2 genes. Polysaccharides exhibited the growth inhibitory effects on cancer cells lines of AGS, MKN-28 and MKN-45, in which F2 fraction exhibited prominent bioactivities. The AGS cells treated with F2 experienced condensed cytoplasm, shrinkage of nucleus and chromatin marginalization with the highest number of cells at early-stage apoptosis reaching 54.6%. The inhibitory effect of F2 polysaccharide on AGS cells was through MAPKs and STAT3 signaling pathways. The backbone of the F2 was mainly linked by (1 â†’ 4)-linked mannopyranosyl and (1 â†’ 3)-linked galactopyranosyl. Taken together, the polysaccharide from A. asphodeloides rhizomes could be utilized as medicinal, pharmacological and functional food ingredients.


Subject(s)
Anemarrhena/chemistry , Gene Expression Regulation/drug effects , Immunologic Factors/pharmacology , Polysaccharides/pharmacology , Rhizome/chemistry , Animals , Apoptosis/drug effects , Apoptosis/genetics , Carbohydrate Sequence , Cell Line, Tumor , Chromatin/chemistry , Chromatin/drug effects , Chromatin/immunology , Cyclooxygenase 2/genetics , Cyclooxygenase 2/immunology , Cytoplasm/drug effects , Cytoplasm/immunology , Cytoplasm/pathology , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Interleukin-1/genetics , Interleukin-1/immunology , Mice , Mitogen-Activated Protein Kinases/genetics , Mitogen-Activated Protein Kinases/immunology , Monosaccharides/chemistry , Monosaccharides/isolation & purification , Nitric Oxide/biosynthesis , Polysaccharides/chemistry , Polysaccharides/isolation & purification , RAW 264.7 Cells , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/immunology , Signal Transduction , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology , Uronic Acids/chemistry , Uronic Acids/isolation & purification
19.
Curr Pharm Biotechnol ; 22(5): 672-681, 2021.
Article in English | MEDLINE | ID: mdl-32634081

ABSTRACT

BACKGROUND: Timosaponin A-III is one of the most promising active saponins from Anemarrhena asphodeloides Bge. As an oral chemotherapeutic agent, there is an urgent need to clarify its biopharmaceutics and pharmacokinetics to improve its development potential. OBJECTIVE: This research explores the bioavailability of timosaponin A-III and clarifies its absorption and metabolism mechanisms by a sensitive and specific HPLC-MS/MS method. METHODS: Pharmacokinetics and bioavailability studies of timosaponin A-III were performed in Sprague- Dawley rats by oral (20 mg/kg) and intravenous administration (2 mg/kg). Control group was given the same volume of normal saline. The absorption of timosaponin A-III was investigated in a rat intestinal perfusion model in situ and a Caco-2 cell transport model in vitro. The metabolic rate of timosaponin A-III was determined in a rat liver microsome incubation system. RESULTS: After the oral administration, timosaponin A-III reached Cmax of 120.90 ± 24.97 ng/mL at 8 h, and the t1/2 was 9.94 h. The absolute oral bioavailability of timosaponin A-III was 9.18%. The permeability coefficients of timosaponin A-III in four intestinal segments ranged from 4.98 to 5.42 × 10-7 cm/s, indicating a difficult absorption. A strikingly high efflux transport of timosaponin A-III was found, PappBA 3.27 ± 0.64 × 10-6 cm/s, which was abolished by a P-gp inhibitor. Rat liver microsome incubation studies showed that timosaponin A-III could hardly be metabolized, with a t1/2 of over 12 h. In addition, the solubility test showed a low solubility in PBS solution, i.e. 30.58 µg/mL. CONCLUSION: Timosaponin A-III exhibited low oral bioavailability by oral and intravenous administration, which was probably caused by its low permeability and solubility. This study may provide a reference for its rational clinical use and further study on the pharmacology or toxicology of timosaponin A-III.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacokinetics , Saponins/pharmacokinetics , Steroids/pharmacokinetics , Administration, Intravenous , Administration, Oral , Anemarrhena/chemistry , Animals , Antineoplastic Agents, Phytogenic/chemistry , Biological Availability , Biopharmaceutics , Caco-2 Cells , Chromatography, High Pressure Liquid , Humans , In Vitro Techniques , Male , Microsomes, Liver/metabolism , Rats , Rats, Sprague-Dawley , Saponins/chemistry , Solubility , Steroids/chemistry , Tandem Mass Spectrometry
20.
Biomed Pharmacother ; 133: 110954, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33378992

ABSTRACT

Anemarrhena asphodeloides is an herb widely used to treat symptoms associated with diabetes in traditional Chinese medicine. However, its key components and metabolites have low bioavailability and poor host absorption. To clarify the anti-diabetic mechanism of A. asphodeloides extract (AAE), we examined the anti-diabetic effects of AAE in rats with diabetes induced by a high-fat diet and streptozotocin. Faeces levels of the main components and metabolites of AAE were significantly higher than levels in plasma, which indicated that gut microbiota might play important roles in its anti-diabetic effect. Microbiological studies showed that unabsorbed components increased the diversity of the gut microbiota, enriched potentially beneficial bacteria, and suppressed potentially harmful bacteria. In vitro studies showed that AAE promoted the proliferation of Blautia coccoides, a bacterium with positive implication for diabetes, in a dose-dependent manner. AAE also promoted pancreatic cell regeneration and restored the function of pancreatic islet cells via peroxiredoxin 4 overexpression. Overall, these results suggest that AAE alleviates diabetes via modulating gut microbiota and protein expression.


Subject(s)
Anemarrhena , Bacteria/drug effects , Blood Glucose/drug effects , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Gastrointestinal Microbiome/drug effects , Hypoglycemic Agents/pharmacology , Intestines/microbiology , Islets of Langerhans/drug effects , Plant Extracts/pharmacology , Anemarrhena/chemistry , Animals , Bacteria/growth & development , Biomarkers/blood , Blood Glucose/metabolism , Cell Proliferation/drug effects , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/microbiology , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/microbiology , Diabetes Mellitus, Type 2/pathology , Diet, High-Fat , Dysbiosis , Hypoglycemic Agents/isolation & purification , Inflammation Mediators/blood , Islets of Langerhans/metabolism , Islets of Langerhans/pathology , Lipids/blood , Male , Peroxiredoxins/metabolism , Plant Extracts/isolation & purification , Rats, Wistar , Streptozocin
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