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1.
Phytomedicine ; 91: 153700, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34425474

RESUMO

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is a standard therapy to treat hepatocellular carcinoma (HCC), but often limited for its complications. Ginsenosides, including total ginsenosides (GS), Rg3, Rh2 and CK, have been clinically used as adjuvants of TACE in HCC therapy. However, partial clinical observations concerning the efficacy and safety of the combinational treatment were contradictory. PURPOSE: To investigate the efficacy and safety of TACE and ginsenosides combination for HCC therapy. METHODS: Randomized controlled trials (RCTs) regarding TACE and ginsenosides for HCC up to May 2021 were screened from six databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese VIP Information and Web of Science). The outcomes of tumor response, adverse reactions (ADRs), quality of life (QOL), survival rates (OS) and liver function were extracted and evaluated by meta-analysis, respectively. RESULTS: A total of 18 RCTs with 1308 HCC patients were enrolled, and most of the eligible studies had unclear bias risk. Compared with TACE, combining ginsenosides improved objective response rate [ORR, risk ratio (RR) 1.39, 95% confidence intervals (CI) 1.20∼1.61], disease control rate (DCR, RR 1.21, 95% CI 1.12∼1.30), QOL (RR 1.54, 95% CI 1.25∼1.90), one- (RR 1.37, 95% CI 1.16∼1.62) and two- (RR 1.43, 95% CI 1.06∼1.95) year OS, and A level of Child-pugh, as well as reduced the risks of nausea and vomiting, pyrexia, ache, hyperbilirubinemia, anorexia, fatigue, leukopenia, thrombocytopenia and myelosuppression. Subgroup analyses showed that both short- and long- treatment durations of ginsenosides enhanced the A level of Child-pugh, and reduced nausea and vomiting, ache and hyperbilirubinemia. Besides, combining Rg3 benefited DCR, ORR and QOL, and alleviated nausea and vomiting, hyperbilirubinemia, leukopenia, myelosuppression, thrombocytopenia and α-fetoprotein, while combining GS alleviated nausea and vomiting, ache and hyperbilirubinemia, combining Rh2 alleviated thrombocytopenia, and combining CK alleviated nausea and vomiting, pyrexia, ache and leukopenia, respectively. CONCLUSION: The results suggested that combining ginsenosides could continuously benefit the efficacy and safety of TACE in HCC treatment, and Rg3 is the prior selection during the combination.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Ginsenosídeos , Neoplasias Hepáticas , Carcinoma Hepatocelular/terapia , Terapia Combinada , Ginsenosídeos/farmacologia , Humanos , Neoplasias Hepáticas/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
2.
J Pharm Biomed Anal ; 203: 114186, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34118572

RESUMO

Chang-Kang-Fang formula (CKF), a multi-herbs traditional Chinese medicine (TCM) prescription for treating irritable bowel syndrome (IBS), has been clinically applied in the traditional form of mixed-herb decoction (MHD), or in the modern form of combined single-herb decoction (cSHD, so called dispensing granule decoction) in the near decades, but the chemical consistency between the MHD and cSHD is still unknown. Herein, a new strategy by integrating multiple-chromatographic approaches to characterize both polysaccharides and small molecules was developed to compare the chemical consistency between MHD and cSHD. Sixteen small molecules were simultaneously qualified and quantified by UPLC-QTOF-MS/MS, the molecular weight distribution of polysaccharides was characterized by HPGPC-ELSD, while the monosaccharide composition and total saccharides content were determined by HPLC-PDA and UV-VIS, respectively. It was found that the molecular weight range and monosaccharide composition of polysaccharides, as well as the composition of small molecules, were identical between MHD and cSHD. However, the contents of berberine, epiberberine, coptisine, palmatine, albiflorin and paeoniflorin in MHD were significantly lower than those in cSHD, whereas the content of polysaccharides in MHD was higher than that in cSHD, indicating that there is a significant difference in the quality between MHD and cSHD, in particular for the relative contents of major small molecules and polysaccharides. Whether or not these quality variations affect the efficacy and safety of CKF deserves further investigation.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Medicina Tradicional Chinesa
3.
Commun Biol ; 4(1): 549, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972672

RESUMO

By a pilot trial on investigating immunomodulatory activity and target of ginsenosides, the major bioactive components of ginseng, here we report that structural analogues in herbal medicines hit a shared target to achieve cumulative bioactivity. A ginsenoside analogues combination with definite immunomodulatory activity in vivo was designed by integrating pharmacodynamics, serum pharmacochemistry and pharmacokinetics approaches. The cumulative bioactivity of the ginsenoside analogues was validated on LPS/ATP-induced RAW264.7 macrophages. The potentially shared target NLRP3 involved in this immunomodulatory activity was predicted by systems pharmacology. The steady binding affinity between each ginsenoside and NLRP3 was defined by molecular docking and bio-layer interferometry assay. The activation of NLRP3 inflammasomes in LPS/ATP-induced RAW264.7 was significantly suppressed by the combination, but not by any individual, and the overexpression of NLRP3 counteracted the immunomodulatory activity of the combination. All these results demonstrate that the ginsenoside analogues jointly hit NLRP3 to achieve cumulative immunomodulatory activity.


Assuntos
Ginsenosídeos/química , Ginsenosídeos/farmacologia , Inflamassomos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Panax/química , Fitoterapia , Animais , Inflamassomos/imunologia , Inflamassomos/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR
4.
Food Funct ; 12(9): 3954-3964, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33977937

RESUMO

The therapeutic effects of water extract of ginseng (WEG) on exercise-induced fatigue (EF) have been reported in several previous studies, but the molecular mechanisms involved remain unexplored. In this study, the anti-EF effects of WEG were studied, and the potential mechanisms were discussed. We characterized the chemical components of WEG by ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS) and high performance liquid chromatography coupled with evaporative light scattering detection (HPLC-ELSD), and then examined the anti-EF effects of WEG on a rat model of weight-loaded swimming with a focus on endogenous metabolism and gut microbiota. WEG contains abundant (90.15%, w/w) saccharides and ginsenosides with structurally diverse glycosyls. WEG taken orally showed strong anti-EF effects by ameliorating energy metabolism abnormality, oxidative stress, lipid peroxidation, inflammatory response, disorders in the metabolism of bile acid, amino acid, fatty acid and lipid, as well as the gut microbiota dysbiosis. Given that gut microbiota is significantly associated with energy expenditure, systemic inflammation and host metabolism, these findings suggest a potential central role of the gut microbiota in mediating the anti-EF effect of WEG. That is, the saccharides and ginsenosides in WEG serve as energy substrates for specific intestinal bacteria, thereby beneficially regulating the gut microbiota, and the reshaped gut microbial ecosystem then triggers several molecular and cellular signaling pathways (e.g. butyrate or TGR5 signals) to achieve the therapeutic effects on EF. The outcomes highlighted here enable deeper insight into how WEG overcomes EF.


Assuntos
Fadiga/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Panax , Esforço Físico , Extratos Vegetais/farmacologia , Aminoácidos/metabolismo , Animais , Bacteroidetes/classificação , Bacteroidetes/crescimento & desenvolvimento , Bacteroidetes/isolamento & purificação , Ácidos e Sais Biliares/metabolismo , Disbiose , Fadiga/etiologia , Ácidos Graxos/metabolismo , Firmicutes/classificação , Firmicutes/crescimento & desenvolvimento , Firmicutes/isolamento & purificação , Metabolismo dos Lipídeos , Masculino , Metaboloma , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-Dawley , Natação
5.
Food Funct ; 12(5): 2225-2241, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33595586

RESUMO

Chemotherapy is applied to treat non-small cell lung cancer (NSCLC), but often limited due to its unstable therapeutic effects and adverse reactions (ADRs). Ginseng and its main ingredients (ginsenosides and polysaccharides) have been clinically used as adjuvants to chemotherapy. However, their efficacies were based on individual trials with relatively small sample sizes, and it is difficult to draw a valid conclusion. In this study, eligible randomized controlled trials (RCTs) were searched in six international and Chinese databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese VIP Information and Wanfang). The outcomes of the objective response rate (ORR), disease control rate (DCR), ADRs, quality of life (QOL), survival rates and immunity were extracted using standard data extraction forms. The efficacies of ginseng and its ingredients as adjuvants to chemotherapy in NSCLC were investigated and compared by meta-analysis and subgroup meta-analysis, respectively. A total of 28 RCTs including 2503 subjects were enrolled, and most of the eligible studies were of low-to-moderate quality. For the evaluation of ginseng and its ingredients as adjuvants to chemotherapy, the risk ratio (RR) or standardized mean difference (SMD) and 95% confidence intervals (CI) of the ORR, DCR, leucopenia, thrombocytopenia, myelosuppression, hepatotoxicity, nausea and vomiting, diarrhea, CD4+/CD8+ and one- and two-year survival rates, and QOL were 1.35 (1.21,1.50), 1.20 (1.14,1.28), 0.59 (0.50, 0.70), 0.53 (0.37, 0.76), 0.30 (0.17, 0.53), 0.67 (0.52, 0.87), 0.67 (0.53, 0.86), 0.42 (0.19, 0.96), 1.39 (0.63, 2.16), 1.35 (1.13, 1.60), 3.21 (1.51, 6.81) and 1.31 (1.22, 1.41) with significant differences. Subgroup analysis showed that ginseng enhanced nausea and vomiting and QOL, ginsenosides increased ORR, DCR, QOL, leucopenia, thrombocytopenia, myelosuppression, hepatotoxicity, diarrhea, CD4+/CD8+, and one- and two-year survival rates, while polysaccharides improved ORR, DCR, leucopenia, thrombocytopenia, myelosuppression, hepatotoxicity and nausea and vomiting during chemotherapy. In conclusion, ginseng and its ingredients facilitated the therapeutic effects of chemotherapy on NSCLC patients. Ginseng had beneficial effects on alleviating ADRs and enhancing QOL, ginsenosides demonstrated beneficial effects on enhancing therapeutic effects, reducing ADRs, improving immunity, prolonging survival rates and promoting QOL, while polysaccharides showed beneficial effects on promoting therapeutic effects and reducing ADRs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Panax , Extratos Vegetais/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Quimioterapia Adjuvante , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/fisiopatologia , Pessoa de Meia-Idade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
J Pharm Biomed Anal ; 192: 113665, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33120311

RESUMO

Cicadae Periostracum (CP), the cast-off shell of Cryptotympana atrata, is specified in Chinese Pharmacopoeia for relieving fever and eliminating ulcer. N-acetyldopamine oligomers are the major characteristic bioactive components with antioxidant and anti-inflammatory activities that may be responsible for the efficacy of CP. However, the exposed components and metabolites of N-acetyldopamine oligomers of CP (NOCP) in vivo are still unknown. In present study, the metabolic profile of total NOCP and N-acetyldopamine dimer B in rats were systematically investigated by ultra-high liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). In biosamples of NOCP group, 34 prototypes and 15 metabolites were identified or tentatively characterized, including 5 metabolites in plasma, 3 prototype and 9 metabolites in urine, 2 metabolites in bile, 34 prototypes and 8 metabolites in feces, respectively. In dimer B group, the prototype and 8 metabolites were identified, including 2 metabolites in plasma, 4 metabolites in urine, 1 metabolite in bile and 5 metabolites in feces, respectively. Oxidation, and hydrogenation were supposed to be the major phase I reactions, while methylation, sulfation, and glucuronidation were the main phase II reactions of NOCP and dimer B. M10 and M13 might undergo enterohepatic circulation in rats. It is concluded that NOCP and dimer B were mainly absorbed in the form of metabolites, and metabolites are probably the major bioactive forms of NOCP and dimer B. The outcomes of this study provided helpful information for extensively elucidating biological and pharmacological mechanisms of NOCP.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão , Dopamina/análogos & derivados , Ratos , Ratos Sprague-Dawley
7.
Eur J Drug Metab Pharmacokinet ; 46(1): 93-104, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32894450

RESUMO

BACKGROUND AND OBJECTIVE: Ginseng is usually consumed as a dietary supplement for health care in the normal state or prescribed as a herbal medicine in pathologic conditions. Although metabolic studies of ginseng are commonly performed on healthy organisms, the metabolic characteristics in pathologic organisms remain unexplored. This study aimed to uncover the difference in intestinal metabolism of ginseng between normal and cyclophosphamide-induced immunosuppressed rats and further discuss the potential mechanisms involved. METHODS: Twelve Sprague-Dawley rats (6-8 weeks old) were randomly divided into two groups: the normal group (NG) and immunosuppressed group (ISG). Rats in the NG and ISG groups were intraperitoneally administered normal saline and cyclophosphamide injections (40 mg/kg) on the 1st, 2nd, 3rd and 10th days; on the 12th day, all rats were intragastrically administered ginseng water extract (900 mg/kg). The difference in intestinal metabolism of ginseng was compared using an ultra-high-performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry-based metabolomics approach, and the diversities of gut microbiota were analyzed by 16S rRNA gene sequencing between the two groups. RESULTS: The intestinal metabolomic characteristics of ginseng were significantly different between the normal and immunosuppressed rats, with the ginsenoside F2 (F2), 20S-ginsenoside Rg3 (20(S)-Rg3), pseudo-ginsenoside Rt5 (Pseudo-Rt5), ginsenoside Rd (Rd), ginsenoside Rh1 (Rh1), 20S-ginsenoside Rg1 (20(S)-Rg1), ginsenoside compound K (CK), ginsenoside Rg2 (Rg2) and 20S-panaxatriol (S-PPT) more abundant in immunosuppressed ones (P < 0.05). Additionally, the composition of gut microbiota was remarkably altered in the two groups, with some specific bacterial communities such as Bacteroides spp., Eubacterium spp. and Lachnospiraceae_UCG-010 spp. increased and Bifidobacterium spp. decreased in immunosuppressed rats compared with normal ones. CONCLUSION: The intestinal metabolism of ginseng in immunosuppressed rats was significantly different from that in normal ones, which might be partly attributed to the changes in the intensity of specific gut bacteria. The outcomes of this study could provide scientific data for rationalization of ginseng use as both a dietary supplement and herbal medicine.


Assuntos
Tolerância Imunológica/efeitos dos fármacos , Imunossupressores/toxicidade , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Panax , Extratos Vegetais/farmacologia , Animais , Ciclofosfamida/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Ginsenosídeos/isolamento & purificação , Ginsenosídeos/farmacologia , Tolerância Imunológica/imunologia , Mucosa Intestinal/imunologia , Masculino , Extratos Vegetais/isolamento & purificação , Ratos , Ratos Sprague-Dawley
8.
J Ethnopharmacol ; 269: 113722, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33352240

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Poria cocos (Schw.) Wolf (Poria) is a well-known traditional medicinal fungus. It has been considered to possess spleen-invigorating (Jianpi) effects in traditional Chinese medicine, and is used clinically to treat spleen deficiency (Pixu) with symptoms of intestinal disorders such as diarrhea, indigestion, mucositis and weight loss. THE AIM OF THIS STUDY: To investigate the protective effects of Poria and its three component fractions (Water-soluble polysaccharides, WP; alkali-soluble polysaccharides, AP; triterpene acids, TA) on cisplatin-induced intestinal injury and explore the underlying mechanisms. MATERIALS AND METHODS: C57BL/6 mice were treated with Poria powder (PP), WP, AP and TA by oral gavage respectively for 13 days, and intraperitoneally injected with 10 mg/kg of cisplatin on day 10 to conduct a cisplatin-induced intestinal injury model. Pathological changes of ileum and colon were examined using H&E staining. The composition of gut microbiota and the alteration of host metabolites were characterized by 16S rDNA amplicon sequencing and UPLC-QTOF-MS/MS based untargeted metabolomics analysis. RESULTS: PP and WP attenuated the cisplatin-induced ileum and colon injury, and WP alleviated the weight loss and reversed the elevation of IL-2, IL-6 in serum. Both PP and WP could mitigate cisplatin-induced dysbiosis of gut microbiota, in particular PP and WP decreased the abundance of pathogenic bacteria including Proteobacteria, Cyanobacteria, Ruminococcaceae and Helicobacteraceae, while WP promoted the abundance of probiotics, such as Erysipelotrichaceae and Prevotellaceae. Moreover, WP attenuated the cisplatin-induced alteration of metabolic profiles. The levels of potential biomarkers, including xanthine, L-tyrosine, uridine, hypoxanthine, butyrylcarnitine, lysoPC (18:0), linoleic acid, (R)-3-hydroxybutyric acid, D-ribose, thiamine monophosphate, indolelactic acid and plamitic acid, showed significant correlations with intestinal flora. CONCLUSIONS: PP and WP possess protective effects against cisplatin-induced intestinal injury via potentially regulating the gut microbiota and metabolic profiles.


Assuntos
Enteropatias/prevenção & controle , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Wolfiporia/química , Álcalis/química , Animais , Biomarcadores Farmacológicos/análise , Peso Corporal/efeitos dos fármacos , Cisplatino/toxicidade , Citocinas/sangue , Modelos Animais de Doenças , Disbiose/induzido quimicamente , Disbiose/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Enteropatias/induzido quimicamente , Enteropatias/patologia , Masculino , Medicina Tradicional Chinesa , Metaboloma/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Pós/administração & dosagem , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/química , Triterpenos/química , Água/química
9.
J Ethnopharmacol ; 265: 113251, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32810615

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Application of cyclosporine A (CsA) as a rescue treatment in acute severe ulcerative colitis (UC) is limited by its narrow therapeutic window and great interpatient variability. As a substrate of cytochrome P450 3A enzyme (CYP3A) and P-glycoprotein (P-gp), the oral pharmacokinetics of CsA is susceptible to disease status and concomitant medications. Combined treatment with ginseng, a famous medicinal herb frequently prescribed for ameliorating abnormal immune response in many diseases including UC, showed immunologic safety in CsA-based immunosuppression. AIM OF THE STUDY: Since the therapeutic levels of CsA can be achieved within 24 h, this study first assessed the impact of acute colitis and ginseng intervention on the single oral dose pharmacokinetics of CsA and explored the underlying mechanisms in dextran sulfate sodium (DSS)-induced colitis rats and Caco-2 cells. MATERIALS AND METHODS: Rats received drinking water (normal group), 5% DSS (UC group), or 5% DSS plus daily oral ginseng extract (GS+UC group). On day 7, GS+UC group only received an oral dose of CsA (5 mg/kg), while animals of normal or UC group received an oral, intravenous (1.25 mg/kg), or intraperitoneal dose of CsA (1.25 mg/kg), respectively. Blood, liver/intestine tissues and fecal samples were collected for determining CsA and main hydroxylated metabolite HO-CsA or measuring hepatic/intestinal CYP3A activity. Caco-2 cells were incubated with gut microbial culture supernatant (CS) of different groups or ginseng (decoction or polysaccharides), and then CYP3A, P-gp and tight junction (TJ) proteins were determined. RESULTS: Oral CsA exhibited enhanced absorption, systemic exposure and tissue accumulation, and lower fecal excretion, while intravenous or intraperitoneal CsA showed lower systemic exposure and enhanced distribution, in colitis rats. Diminished intestinal and hepatic P-gp expression well explained the changes with DSS-induced colitis. Moreover, blood exposures of HO-CsA in both normal and colitis after oral dosing were significantly higher than intravenous/intraperitoneal dosing, supporting the dominant role of intestinal first-pass metabolism. Interestingly, colitis reduced CYP3A expression in intestine and liver but only potentiated intestinal CYP3A activity, causing higher oral systemic exposure of HO-CsA. Oral ginseng mitigated colitis-induced down-regulation of CYP3A and P-gp expression, facilitated HO-CsA production, biliary excretion and colonic sequestration of CsA, while not affected CsA oral systemic exposure. In Caco-2 cells, gut microbial CS from both colitis and GS+UC group diminished P-gp function, while ginseng polysaccharides directly affected ZO-1 distribution and suppressed TJ proteins expression, explaining unaltered oral CsA systemic exposure. CONCLUSIONS: DSS-induced colitis significantly altered oral CsA disposition through regulating intestinal and hepatic P-gp and CYP3A. One-week ginseng treatment enhanced colonic accumulation while not altered the systemic exposure of CsA after single oral dosing, indicating pharmacokinetic compatibility between the two medications.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Ciclosporina/farmacocinética , Panax/química , Extratos Vegetais/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Administração Oral , Animais , Células CACO-2 , Colite Ulcerativa/fisiopatologia , Ciclosporina/administração & dosagem , Citocromo P-450 CYP3A/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Interações Ervas-Drogas , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Mucosa Intestinal/metabolismo , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
10.
J Ethnopharmacol ; 265: 113271, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32853742

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cyclophosphamide (CTX) is a first line chemotherapeutic agent, but often limited for its unstable therapeutic effect and serious side effects. Ginsenosides could facilitate the anti-tumor efficiency of CTX, including benefiting therapeutic effect and decreasing side effects. AIM OF THE STUDY: To investigate the potential mechanism of ginsenosides on benefiting the anti-tumor efficiency of CTX. MATERIALS AND METHODS: Mammary carcinoma mice were applied to investigate the anti-tumor efficiency and potential mechanism of combinational treatment of ginsenosides and CTX. Therapeutic effect was evaluated based on survival rate, tumor burden, tumor growth inhibition rate, and apoptosis and histological changes of tumor tissues. Anti-tumor immunity was studied by measuring serum level of anti-tumor cytokines. Gut mucositis, one of lethal side effects of CTX, was evaluated by diarrhea degree, gut permeability and tight junction proteins expressions. Gut microbial diversity was analyzed by 16S rRNA gene sequencing, and fecal transplant and antibiotics sterilized animals were performed to evaluate the therapeutic effect of gut microbiota on tumor suppression. RESULTS: Ginsenosides facilitated the therapeutic effect of CTX in mice, which manifested as prolonged survival rate, decreased tumor burden, as well as enhanced tumor growth inhibition rate and apoptosis. The favoring effect was related to elevation of anti-tumor immunity which manifested as the increased anti-tumor cytokines (INF-γ, IL-17, IL-2 and IL-6). Further studies indicated the elevation was ascribed to ginsenosides promoted reproduction of gut probiotics including Akkermansia, Bifidobacterium and Lactobacillus. Moreover, co-administration of ginsenosides in mice alleviated CTX-induced gut mucositis, including lower gut permeability, less diarrhea, less epithelium damage and higher tight junction proteins. Further researches suggested the alleviation was related to ginsenosides activated Nrf2 and inhibited NFκB pathways. CONCLUSION: Ginsenosides show dual roles to facilitate the anti-tumor efficiency of CTX, namely promote the anti-tumor immunity through maintaining gut microflora and ameliorate gut mucositis by modulating Nrf2 and NFκB pathways.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Ciclofosfamida/farmacologia , Ginsenosídeos/farmacologia , Neoplasias Mamárias Experimentais/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Apoptose/efeitos dos fármacos , Ciclofosfamida/administração & dosagem , Citocinas/sangue , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Ginsenosídeos/administração & dosagem , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos ICR , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , RNA Ribossômico 16S , Taxa de Sobrevida
11.
Food Funct ; 11(11): 9740-9751, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33064121

RESUMO

In the present study, the hypoglycemic effects of glucomannan (AGM) and its enzyme-degraded products from Amorphophallus albus were investigated. Four degraded products were prepared through ultrafiltration of ß-glucanase-degraded products of AGM. The hypoglycemic activities were evaluated in HFD-STZ-induced type 2 diabetes mellitus (T2DM) mice, and the diversity of gut bacteria was analyzed by 16S rRNA gene sequencing; the fecal short chain fatty acids (SCFAs) and endogenous metabolites were determined by UPLC-QTOF-MS/MS. It was found that AGM and its enzyme-degraded products, though with different molecular weights, had similar ß-glycosidic bonds and monosaccharide compositions, exerted similar strength of hypoglycemic effects, and reinstated with a similar extent the disordered gut microbiota and the contents of SCFAs and endogenous metabolites. It was speculated that the hypoglycemic activity of AGM is decided by not the molecular weight but the glycosidic bonds/monosaccharide composition of AGM, which might be structurally specific to the gut bacteria, and thus certain SCFAs and endogenous metabolites that are related to the occurrence and therapy of T2DM. This study provides a scientific basis for using AGM as potential prebiotics beneficial for prevention or therapeutic treatment of T2DM.


Assuntos
Amorphophallus , Hipoglicemiantes/farmacologia , Mananas/farmacologia , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Modelos Animais de Doenças , Alimento Funcional , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Prebióticos
12.
J Pharm Biomed Anal ; 191: 113581, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32892083

RESUMO

Sulfur fumigation and heating desulfurization are used together in the post-harvest processing of many medicinal herbs. However, little is known about the effects of sulfur fumigation on saccharide components, nor about the effects of heating desulfurization on all herbal constituents. In this study, metabolomics and glycomics were integrated to investigate the effects of these two processes on the chemistry of Codonopsis Radix (CR) as a pilot study. The results showed that both sulfur fumigation and heating desulfurization significantly changed the non-saccharide small-molecule metabolome and the glycome of CR in different ways. Chemical mechanisms, such as esterification, glycosidic hydrolysis, esterolysis, amide bond hydrolysis, oxidation and dehydration, are proposed to be involved. These facts strongly inspire that, in addition to investigations of how sulfur fumigation impacts non-saccharide small-molecule metabolites, researches on heating desulfurization and saccharides should be conducted so as to enable accurate, comprehensive evaluation of the quality of sulfur-fumigated herbs.


Assuntos
Codonopsis , Medicamentos de Ervas Chinesas , Plantas Medicinais , Fumigação , Glicômica , Calefação , Metabolômica , Projetos Piloto , Enxofre
13.
J Ethnopharmacol ; 256: 112799, 2020 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-32243989

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sulfur-fumigation has been developed to prevent insects and molds during post-harvest handling of Panax ginseng C.A. Mey (ginseng) in the near decades. Our previous study indicated sulfur-fumigation could transform ginsenosides, the active components of ginseng, into sulfur-containing derivatives (SFCDs), the artifacts with unknown toxicity. However, whether the biotransformation could be occurred and absorption characteristics between ginsenosides and SFCDs are still needed to further investigate. AIM OF THE STUDY: To evaluate the effect of sulfur-fumigation process on ginseng through comparing the metabolic profile and absorption characteristics between ginsenoside Rg1, Re and their SFCDs. MATERIALS AND METHODS: Intestinal microflora and liver S9 fraction were utilized to compare the metabolic profile, and single-pass intestinal perfusion and Caco-2 cell models were applied to compare the absorption characteristics, between Rg1, Re and their SFCDs. RESULTS: Rg1 and Re were metabolized to 7 none sulfur-containing metabolites, while their SFCDs were metabolized to 18 sulfur-containing metabolites. The intestinal absorption and transport of Rg1 and Re were much greater than their SFCDs. Besides, the uptakes of Rg1 and Re were transport-dependent, but their SFCDs were non-transport-dependent. CONCLUSION: Ginsenosides and their SFCDs could not be bio-transformed with each other and their absorption characteristics were quite different, which suggested that sulfur-fumigation is not a feasible post-harvest process of ginseng.


Assuntos
Absorção Intestinal/efeitos dos fármacos , Panax/química , Enxofre/farmacologia , Animais , Biotransformação/efeitos dos fármacos , Células CACO-2 , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão/métodos , Fumigação/métodos , Ginsenosídeos/farmacologia , Humanos , Intestinos/efeitos dos fármacos , Masculino , Metaboloma/efeitos dos fármacos , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley
14.
J Pharm Biomed Anal ; 179: 112974, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31767224

RESUMO

Cicadae Periostracum, which is derived from the slough of Cicadidae insects, is a commonly used crude drug in traditional Chinese medicine (TCM). As specified in Chinese Pharmacopoeia, Cryptotympana atrata (CA) is the only official species of this crude drug. However, the slough of other three species, i.e., Auritibicen flammatus (AF), Cryptotympana mandrina (CM) and Platypleura kaempferi (PK), have been also used as the origins of Cicadae Periostracum in Chinese herbal market, although whether the quality of these four origins is consistent or not is still unknown. In present study, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was employed to qualitatively and quantitatively compare the chemical profiles of the four origins. Totally, 34 N-acetyldopamine polymers were identified from the four origins, including 4 N-acetyldopamine dimers, 11 N-acetyldopamine trimers, 10 N-acetyldopamine tetramers, and 9 N-acetyldopamine pentamers. AF, CM and PK had similar chemical profiles with that of CA. The contents and compositional ratio of the four types of polymers in CA, AF and CM were consistent with each other, but significantly lower or different in PK. All these results suggested that AF and CM might be considered as the potential resources of Cicadae Periostracum concerning their consistent holistic quality, whereas whether PK could be used as potential origin of Cicadae Periostracum or not need further evaluation for their different compositional ratios and contents of the four types of N-acetyldopamine polymers. This is the first study on chemical profiling and comparison of N-acetyldopamine polymers in four origins of Cicadae Periostracum, which is beneficial for potential resources utilization and quality standard improvement of Cicadae Periostracum.


Assuntos
Dopamina/análogos & derivados , Medicamentos de Ervas Chinesas/química , Hemípteros/química , Animais , Cromatografia Líquida de Alta Pressão , Dopamina/análise , Polímeros/análise , Espectrometria de Massas em Tandem
15.
Phytomedicine ; 74: 152761, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31005370

RESUMO

BACKGROUND: Ginseng has therapeutic potential for treating obesity and the associated gut microbiota dysbiosis. However, whether white ginseng and red ginseng, the two kinds of commonly used processed ginseng, possess different anti-obesity effects remains unknown. PURPOSE: Anti-obesity effects of water extracts of white ginseng and red ginseng (WEWG and WERG) were compared, and the potential mechanisms were discussed. METHODS: Chemical profiles of WEWG and WERG were characterized by ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS) and high performance liquid chromatography coupled with evaporative light scattering detector (HPLC-ELSD). Anti-obesity effects of WEWG/WERG were examined by determining fat accumulation, systemic inflammation, enteric metabolic disorders and gut microbiota dysbiosis in high-fat diet (HFD)-fed obese mice. RESULTS: Both WEWG and WERG exerted anti-obesity effects, with WEWG stronger than WERG. Compared to WERG, WEWG contained less contents of carbohydrates (polysaccharides, oligosaccharides, free monosaccharides) and ginsenosides, but chemical structures or compositions of these components in WEWG were characteristic, i.e. narrower molecular weight distribution and higher molar ratios of glucose residues of polysaccharides; higher content ratios of oligosaccharides DP2-3 (di-/tri-saccharides)-to-oligosaccharides DP4-7 (tetra-/penta-/hexa-/hepta-saccharides), sucrose-to-melibiose, maltose-to-trehalose and high-polar-to-low-polar ginsenosides. WEWG better ameliorated fat accumulation, enteric metabolic disorders and gut microbiota dysbiosis in HFD-fed obese mice than WERG. CONCLUSION: The stronger anti-obesity effect of white ginseng appears to correlate with differences in its chemical profile as compared to red ginseng. The carbohydrates and ginsenosides in WEWG potentially present more structural and compositional specificity to the obesity-associated gut bacteria, allowing more beneficial effects of WEWG on the gut microbiota dysbiosis. This consequently better alleviates the enteric metabolic disorders and systemic inflammation, thereby contributing to the stronger anti-obesity effect of WEWG as compared to WERG.


Assuntos
Fármacos Antiobesidade/farmacologia , Disbiose/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/tratamento farmacológico , Panax/química , Animais , Fármacos Antiobesidade/química , Carboidratos/análise , Cromatografia Líquida de Alta Pressão , Dieta Hiperlipídica/efeitos adversos , Disbiose/microbiologia , Microbioma Gastrointestinal/fisiologia , Ginsenosídeos/análise , Masculino , Camundongos Endogâmicos BALB C , Obesidade/microbiologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/análise , Especificidade da Espécie , Espectrometria de Massas em Tandem
16.
J Chromatogr A ; 1608: 460418, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31420179

RESUMO

High performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (HPLC-QTOF-MS) is widely used to qualitatively characterize the chemical profiles of herbal medicines, in which the generated adducts and fragments are crucial for confirming molecular ion (deprotonated/protonated ion) and deducing structure of detected components. However, how chromatographic and mass spectrometric (LC-MS) conditions/parameters affect the quantity and intensity of adducts and fragments of detected components is scarcely concerned. In present study, three types of triterpene saponins from the root of Ilex asprella (RIA) were selected as a case study to systematically investigate the effects of LC/MS conditions/parameters on their ionization and fragmentation, so as to obtain higher intensity (higher detection sensitivity) and quantity (rich information) of adducts and fragments for the characterization of components in RIA. It was found that for LC conditions, methanol as organic phase was more benefit for generating more adducts with higher intensity; formic acid as a modifier suppressed the formation of [M-2H]2-, thus promoted the generation of other types of adducts at lower concentration but inhibited the generation when the concentration exceeded 0.1%. MS parameters affect scarcely the quantity but mainly intensity of adducts, cone voltage, source temperature and desolvation gas flow have relatively higher impacts when compared with other parameters. Collision energy affected both quantity and intensity of fragments. MS parameters at the medium value largely increased the quantity and intensity of adducts and fragments. Three-types of triterpene saponins presented structurally specific ionization and fragmentation due to their amounts of acidic substitutes. A total of 55 components were detected and definitely or tentatively identified in RIA under the optimized LC-MS conditions, among which 35 triterpene saponins were firstly discovered. This is the first report that proposes and validates a systematic approach for assessing the effects of LC/MS conditions/parameters on the ionization and fragmentation of analytes, which could be helpful for the optimization of LC-MS conditions for effective chemical profiling analysis of herbal medicines.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ilex/química , Extratos Vegetais/química , Saponinas/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Triterpenos/química , Estrutura Molecular , Plantas Medicinais/química
18.
Phytochem Anal ; 30(4): 447-455, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30916852

RESUMO

INTRODUCTION: The Chinese medicine formulation, tumour-shrinking decoction (TSD, FM1523), which consists of 15 natural medicines, is used for uterine fibroids (UFs) therapy and possesses excellent clinical therapeutic effect. OBJECTIVE: To develop a sensitive and validated analytical method for the simultaneous quantification of four crucial bioactive compounds including isorhamnetin-3-O-neohesperidoside, curcumin, peimine and tetrahydropalmatine in the principal formulation of this decoction. METHODS: An ultra-performance liquid chromatography coupled tandem mass spectrometry (UPLC-MS/MS) with an electrospray ionisation (ESI) source in multiple reaction monitoring (MRM) mode was conducted to investigate these bioactive compounds in the TSD. The chromatographic separation was performed on a C18 column when the flow rate was adjusted at 0.2 mL/min with gradient elution of acetonitrile-water with 0.1% formic acid. Accelerated solvent extraction (ASE) method with higher extraction efficiency was employed for TSD sample pre-treatment. RESULTS: The linearity, limit of detection (LOD) and limit of quantification (LOQ) were determined for this analytical method. The mean recoveries of the compounds were determined between 100.23% and 104.02% with satisfactory relative standard deviation (RSD) in the ranges of 2.65% to 3.81%. The precision was evaluated by intra-day and inter-day tests, which revealed RSD within the ranges of 1.21% to 2.14% and 1.24% to 2.32%, respectively. CONCLUSION: The bioactive compounds of TSD samples were successfully quantified via UPLC-MS/MS with MRM mode. This study could help to evaluate the pharmacokinetic study of TSD during clinical applications and present a facile strategy for quantifying bioactive compounds in traditional Chinese Medicine decoction.


Assuntos
Alcaloides de Berberina/química , Cevanas/química , Medicamentos de Ervas Chinesas/química , Leiomioma/tratamento farmacológico , Compostos Fitoquímicos/química , Alcaloides de Berberina/isolamento & purificação , Cevanas/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Humanos , Limite de Detecção , Compostos Fitoquímicos/isolamento & purificação , Espectrometria de Massas em Tandem
19.
ACS Nano ; 13(2): 2654-2662, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30730697

RESUMO

The spatially precise integration of arrays of micropatterned two-dimensional (2D) crystals onto three-dimensionally structured Si/SiO2 substrates represents an attractive, low-cost system-on-chip strategy toward the realization of extended functions in silicon microelectronics. However, the reliable integration of such atomically thin arrays on planar patterned surfaces has proven challenging due to their poor adhesion to underlying substrates, as ruled by weak van der Waals interactions. Here, we report on an integration method utilizing the flexibility of the atomically thin crystals and their physical subsidence in liquids, which enables the reliable fabrication of the micropatterned 2D materials/Si arrays. Our photodiode devices display peak sensitivity as high as 0.35 A/W and external quantum efficiency (EQE) of ∼90%. The nano-subsidence technique represents a viable path to on-chip integration of 2D crystals onto silicon for advanced microelectronics.

20.
Phytochem Anal ; 30(3): 292-310, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30569602

RESUMO

INTRODUCTION: Triterpene acids from the dried sclerotia of Poria cocos (Schw.) Wolf (poria) were recently found to possess anti-cancer activities. Identification of more triterpene acid analogues in poria is worthwhile for high throughput screening in anti-cancer drug discovery. OBJECTIVE: To establish an efficient dereplication strategy for identifying triterpene acid analogues in poria based on ultra-performance liquid chromatography with electrospray ionisation quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-QTOF-MS/MS). METHODOLOGY: The structural characteristics and mass spectrometric data profiles of known triterpene acids previously reported in poria were used to establish a predicted-analogue database. Then, the quasi-molecular ions of components in a poria extract were automatically compared with those in the predicted-analogue database to highlight compounds of potential interest. Tentative structural identification of the compounds of potential interest and discrimination of isomers were achieved by assessing ion fragmentation patterns and chromatographic behaviour prediction based on structure-retention relationship. RESULTS: A total of 62 triterpene acids were unequivocally or tentatively characterised from poria, among which 17 triterpene acids were tentatively identified for the first time in poria. CONCLUSION: This study provided more structure information of triterpene acids in poria for future high throughput screening of anti-cancer candidates. It is suggested that this semi-automated approach in which MS data are automatically compared to a predictive database may also be applicable for efficient screening of other herbal medicines for structural analogues of proven bioactives.


Assuntos
Ácidos/química , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Triterpenos/análise , Wolfiporia/química , Mineração de Dados , Padrões de Referência , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/normas
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