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1.
Angew Chem Int Ed Engl ; : e202404295, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649323

RESUMO

Homogeneous electrocatalysts can indirect oxidate the high overpotential substrates through single-electron transfer on the electrode surface, enabling efficient operation of organic electrosynthesis catalytic cycles. However, the problems of this chemistry still exist such as high dosage, difficult recovery, and low catalytic efficiency. Single-atom catalysts (SACs) exhibit high atom utilization and excellent catalytic activity, hold great promise in addressing the limitations of homogeneous catalysts. In view of this, we have employed Fe-SA@NC as an advanced redox mediator to try to change this situation. Fe-SA@NC was synthesized using an encapsulation-pyrolysis method, and it demonstrated remarkable performance as a redox mediator in a range of reported organic electrosynthesis reactions, and enabling the construction of various C-C/C-X bonds. Moreover, Fe-SA@NC demonstrated a great potential in exploring new synthetic method for organic electrosynthesis. We employed it to develop a new electro-oxidative ring-opening transformation of cyclopropyl amides. In this new reaction system, Fe-SA@NC showed good tolerance to drug molecules with complex structures, as well as enabling flow electrochemical syntheses and gram-scale transformations. This work highlights the great potential of SACs in organic electrosynthesis, thereby opening a new avenue in synthetic chemistry.

2.
Biomed Pharmacother ; 169: 115899, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37984306

RESUMO

As a traditional Chinese medicine, Huangkui capsule (HKC) has been used to treat patients with kidney diseases, including diabetic nephropathy (DN). We have recently demonstrated that HKC could re-regulate the activities of solute carriers (SLC)s in proximal and distal convoluted tubules of kidneys in regression of the development of DN. The main active chemical constituents of HKC are the flavones of Abelmoschus manihot (L.). The current study aims to further evaluate the efficacy of total flavones of A. manihot (TFA) in the regression of DN by analyzing SLC activities in proximal and distal convoluted tubules of kidneys. TFA (0.076 g/kg/d) or vehicle was administered in db/db mice, the animal model of type 2 diabetes and DN, daily via oral gavage for four weeks. Blood glucose levels and urinary albumin-to-creatinine ratio (UACR) were measured and used for the determination of T2D and DN. Ten SLCs, including slc2a2, slc4A1, slc5a2, slc5A3, slc5a8, slc6a20, slc27a2, slc12a3, slc34a1 and slc38a2 were highly expressed in proximal and distinct convoluted tubules of kidneys. Their expression at mRNA and protein levels before and after TFA treatment were analyzed with real-time RT-PCR and immunohistochemistry. Data showed that UACR in the db/db mice after TFA treatment was significantly decreased. Compared with the group of non-diabetic control, slc2a2, slc4A1, slc5a2, slc5A3, slc5a8, slc6a20, slc27a2, slc12a3, slc34a1 and slc38a2 in the group of DN were down-regulated but up-regulated after TFA treatment. Further analyses of whole kidney sections indicated that the numbers and structures of the nephron in db/db mice was increased and improved after TFA treatment. Thereby, the current study provides further evidence that the flavones in A. manihot have pharmacological effects on the treatment of DN by improving the biological function of SLCs in kidneys.


Assuntos
Abelmoschus , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Flavonas , Humanos , Ratos , Camundongos , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Abelmoschus/química , Flavonas/farmacologia , Flavonas/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ratos Sprague-Dawley , Células Epiteliais
3.
Front Pharmacol ; 14: 1215996, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37587982

RESUMO

Introduction: As a traditional Chinese medicine, Abelmoschus manihot (L.) in the form of Huangkui (HK) capsule has been used as a medication for kidney diseases, including diabetic nephropathy (DN), in China. The most significant effect of HK capsule treatment in kidney diseases is the reduction of albuminuria and proteinuria. To evaluate the efficacy of HK capsule in the regression of DN, in the current study, we analyzed the biomarkers in the glomerulus and proximal and distal convoluted tubules in the kidneys of db/db mice, the animal model for type 2 diabetes and DN. Methods: Huangkui capsules (0.84 g/kg/d) or vehicle were administered daily via oral gavage for 4 weeks in db/db mice. Urinary albumin-to-creatinine ratio and blood glucose levels were measured during the whole experimental period. Five biomarkers in the glomerulus and proximal and distal convoluted tubules in the kidneys were selected, namely, col4a3, slc5a2, slc34a1, slc12a3, and slc4a1, and their activities at mRNA and protein levels before and after HK capsule treatment were analyzed by real-time RT-PCR and immunohistochemistry. Result and discussion: After HK capsule treatment for 4 weeks, the urinary albumin-to-creatinine ratio in db/db mice was found to be significantly decreased. The activities of col4a3, slc5a2, slc34a1, slc12a3, and slc4a1 in the kidneys were upregulated in db/db mice prior to the treatment but downregulated after HK capsule treatment. Further analyses of the fields of whole kidney tissue sections demonstrated that the number of nephrons in the kidneys of db/db mice with HK capsule treatment was higher than that in the kidneys of db/db mice without HK capsule treatment. Thereby, the current study provides experimental evidence confirming the medical efficacy of A. manihot in the reduction of albuminuria and proteinuria, suggesting that A. manihot may have pharmacological efficacy in the regression of the development of type 2 diabetes-DN.

4.
Microb Biotechnol ; 16(4): 813-826, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36583468

RESUMO

Huangkui capsule (HKC), a traditional Chinese medicine, has been used for medication of kidney diseases, including diabetic nephropathy (DN). The current study aimed to evaluate the effects of HKC in the modulation of gut microbiota and the amelioration of metabolite levels by using non-obese diabetes (NOD) mice with DN. The microbiota from three parts of intestines (duodenum, ileum and colon) in NOD mice with and without HKC treatment were analysed using 16S rDNA sequencing techniques. Untargeted metabolomics in plasma of NOD mice were analysed with liquid mass spectrometry. Results showed that HKC administration ameliorated DN in NOD mice and the flora in duodenum were more sensitive to HKC intervention, while the flora in colon had more effects on metabolism. The bacterial genera such as Faecalitalea and Muribaculum significantly increased and negatively correlated with most of the altered metabolites after HKC treatment, while Phyllobacterium, Weissella and Akkermansia showed an opposite trend. The plasma metabolites, mainly including amino acids and fatty acids such as methionine sulfoxide, BCAAs and cis-7-Hexadecenoic acid, exhibited a distinct return to normal after HKC treatment. The current study thereby provides experimental evidence suggesting that HKC may modulate gut microbiota and subsequently ameliorate the metabolite levels in DN.


Assuntos
Abelmoschus , Diabetes Mellitus , Nefropatias Diabéticas , Microbioma Gastrointestinal , Ratos , Camundongos , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Rim , Camundongos Endogâmicos NOD , Abelmoschus/química , Ratos Sprague-Dawley , Diabetes Mellitus/metabolismo
5.
J Org Chem ; 86(22): 16121-16127, 2021 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-33599123

RESUMO

The study reported an electrochemically mediated method for the preparation of 2,1-benzoxazoles from o-nitrophenylacetylenes. Different from the traditional electrochemical reduction of nitro to nitroso, the nitro group directly underwent a cyclization reaction with the alkyne activated by selenium cation generated by the anodic oxidation of diphenyl diselenide and finally produced the desired products.


Assuntos
Benzoxazóis , Selênio , Catálise , Ciclização , Oxirredução
6.
Phytother Res ; 35(1): 198-206, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32716080

RESUMO

Abelmoschus manihot, also called as "Huangkui" in Chinese, is an annual flowering herb plant in the family of Malvaceae. As a traditional Chinese medicine, the ethanol extract of the flower in Abelmoschus manihot is made as Huangkui capsule and has been used for medication of the patients with kidney diseases. Its efficacy in clinical symptoms is mainly improving renal function and reducing proteinuria among the patients with chronic kidney disease, diabetic kidney disease or IgA nephropathy. The possible mechanism of Huangkui capsule treatment in kidney diseases may include reducing inflammation and anti-oxidative stress, improving immune response, protecting renal tubular epithelial cells, ameliorating podocyte apoptosis, glomerulosclerosis and mesangial proliferation, as well as inhibiting renal fibrosis. In this review, we first described chemical constituents and pharmacokinetic characteristics in ethanol extract of the flower of Abelmoschus manihot. We then summarized the clinical and epidemiological relevancies of kidney diseases particularly in the mainland of China and discussed the possible molecular mechanisms of Huangkui capsule in the treatment of kidney diseases. Finally, we prospected further research on cellular and molecular mechanisms and application of this Chinese natural medicine in kidney diseases.


Assuntos
Abelmoschus/química , Nefropatias Diabéticas/tratamento farmacológico , Flores/química , Extratos Vegetais/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Animais , China , Medicamentos de Ervas Chinesas/uso terapêutico , Fibrose , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Medicina Tradicional Chinesa , Extratos Vegetais/química , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
J Ethnopharmacol ; 281: 113548, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33152427

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Huangkui capsule (HKC), extracted from Abelmoschus manihot (L.) medic (AM), as a patent proprietary Chinese medicine on the market for approximately 20 years, has been clinically used to treat chronic glomerulonephritis. Renal fibrosis has been implicated in the onset and development of diabetic nephropathy (DN). However, the potential application of HKC for preventing DN has not been evaluated. AIM OF THE STUDY: This study was designed to investigate the efficacy and underlying mechanisms of HKC combined with metformin (MET), the first-line medication for treating type 2 diabetes, in the treatment of renal interstitial fibrosis. MATERIALS AND METHODS: A rat model of diabetes-associated renal fibrosis was established by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg) combined with a high-fat and high-glucose diet. The rats were randomly divided into five groups: normal control, DN, HKC (1.0 g/kg/day), MET (100 mg/kg/d), and HKC plus MET (1.0 g/kg/day + 100 mg/kg/d). Following drug administration for 8 weeks, we collected blood, urine, and kidney tissue for analysis. Biochemical markers and metabolic parameters were detected using commercial kits. Histopathological staining was performed to monitor morphological changes in the rat kidney. High-glucose-induced human kidney HK-2 cells were used to evaluate the renal protective effects of HKC combined with MET (100 µg/mL+10 mmol/L). MTT assay and acridine orange/ethidium bromide were used to examine cell proliferation inhibition rates and apoptosis. Immunofluorescence assay and Western blot analysis were performed to detect renal fibrosis-related proteins including Klotho, TGF-ß1, and phosphorylated (p)-p38. RESULTS: Combination therapy (HKC plus MET) significantly improved the weight, reduced blood glucose (BG), blood urea nitrogen (BUN), total cholesterol (T-CHO), triglycerides (TG), low-density lipoprotein (LDL) and increased the level of high-density lipoprotein (HDL) of DN rats. Combination therapy also significantly reduced urine serum creatinine (SCR) and urine protein (UP) levels as well as reduced the degrees of renal tubule damage and glomerulopathy in DN rats. Combination therapy ameliorated renal fibrosis, as evidenced by reduced levels of alpha-smooth muscle actin and fibronectin and increased expression of E-cadherin in the kidneys. Moreover, HKC plus MET alleviated the degree of DN in part via the Klotho/TGF-ß1/p38MAPK signaling pathway. In vitro experiments showed that combination therapy significantly inhibited cell proliferation and apoptosis and regulated fibrosis-related proteins in high-glucose (HG)-induced HK-2 cells. Further studies revealed that combination therapy suppressed cell proliferation and fibrosis by inhibiting the Klotho-dependent TGF-ß1/p38MAPK pathway. CONCLUSIONS: HKC plus MET in combination suppressed abnormal renal cell proliferation and fibrosis by inhibiting the Klotho-dependent TGF-ß1/p38MAPK pathway. Collectively, HKC combined with MET effectively improved DN by inhibiting renal fibrosis-associated proteins and blocking the Klotho/TGF-ß1/p38MAPK signaling pathway. These findings improve the understanding of the pathogenesis of diabetes-associated complications and support that HKC plus MET combination therapy is a promising strategy for preventing DN.


Assuntos
Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Proteínas Klotho/metabolismo , Metformina/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Experimental , Dieta Hiperlipídica/efeitos adversos , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/administração & dosagem , Glucose/efeitos adversos , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Proteínas Klotho/genética , Masculino , Metformina/administração & dosagem , Fitoterapia , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
8.
Chem Biodivers ; 16(12): e1900467, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31556199

RESUMO

Pulmonary fibrosis (PF) is a chronic obstructive pulmonary disease without effective clinical drug treatment. Qing-Xuan Granule (QX) as a traditional Chinese patent medicine is clinically used to cure children's cough. This study was designed to investigate the effects of QX and possible molecular mechanisms for bleomycin-induced PF. The work used Western blotting and Q-PCR to explore the vitro and vivo mechanisms of QX treatment, while using HPLC-TOF/MS to explore the composition of QX. QX was given daily orally for two weeks after bleomycin intratracheal instillation. The protective effects of QX on lung function, inflammation, growth factors, hydroxyproline content and deposition of extracellular matrix were investigated. QX decreased expression of Col I and α-SMA in lung tissues by down-regulating TGF-ß1-Smad2/3 signaling and suppressed epithelial-mesenchymal transition and effectively reversed abnormal mRNA levels of MMP-1and TIMP-1 as well as LOXL-2 in lung tissues. HPLC-TOF/MS indicate that six substances could be the main active components, which were reported to protect against experimental lung disease.


Assuntos
Substâncias Protetoras/uso terapêutico , Fibrose Pulmonar/tratamento farmacológico , Aminoácido Oxirredutases/genética , Aminoácido Oxirredutases/metabolismo , Animais , Bleomicina/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos C57BL , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Fibrose Pulmonar/induzido quimicamente , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
9.
Phytomedicine ; 57: 203-214, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30785016

RESUMO

BACKGROUND: Huangkui capsule (HKC), an anti-inflammatory Chinese modern patent medicine, has been now widely applied to the clinical therapy of diabetic nephropathy (DN). However, the overall therapeutic mechanisms in vivo are still unclear. Renal tubular epithelial-to-mesenchymal transition (EMT) is one of the major pathogenesis of renal interstitial fibrosis in DN. Recently, the physiological roles of NLRP3 inflammasome activation and toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling are closely linked to EMT. But, it remains elusive whether HKC regulates renal tubular EMT in vivo through targeting NLRP3 inflammasome activation and TLR4/NF-κB signaling in the kidneys. PURPOSE: This study thereby aimed to clarify the therapeutic effects of HKC on renal tubular EMT in DN and its underlying mechanisms in vivo, compared to rapamycin (RAP). METHODS: Thirty-two rats were randomly divided into 4 groups: the Sham group, the Vehicle group, the HKC group and the RAP group. The early DN rat models were induced by unilateral nephrectomy combined with intraperitoneal injection of streptozotocin, and administered with HKC suspension or RAP suspension or vehicle after modeling for 4 weeks. Changes in the incipient renal lesions-related parameters in urine and blood were analyzed, respectively. Renal interstitial tissues were isolated for histomorphometry, immunohistochemistry and Western blotting at sacrifice. RESULTS: For the early DN rat models, HKC at the suitable dose of 2 g/kg/day ameliorated the general condition and biochemical parameters partially including kidney weight (KW), urinary albumin (UAlb), serum creatinine (Scr) and serum albumin (Alb), attenuated renal tubular EMT significantly and inhibited the activation of NLRP3 inflammasome in the kidneys obviously, which was superior to RAP generally. In addition to these, HKC also suppressed TLR4/NF-κB signaling in the kidneys of the DN model rats accurately, which was different from RAP specifically. CONCLUSION: The results of this study further indicated that HKC, different from RAP, can alleviate renal tubular EMT in the DN model rats, likely by inhibiting NLRP3 inflammasome activation and TLR4/NF-κB signaling in the kidneys. Our findings thus provide the more accurate information in vivo about a clinical value of HKC, a traditional anti-inflammatory phytomedicine, in the treatment of the early DN patients.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Modelos Animais de Doenças , Fibrose/tratamento farmacológico , Fibrose/patologia , Inflamassomos/antagonistas & inibidores , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , NF-kappa B/metabolismo , Nefrectomia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia
10.
Aging (Albany NY) ; 10(12): 4197-4212, 2018 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-30585174

RESUMO

The kidney is a typical organ undergoing age and injury. Hyperoside is reported to be useful for preventing aging induced by D-galactose (D-gal). However, therapeutic mechanisms remain unclear. We thereby aimed to verify whether hyperoside, compared to vitamin E (VE), could alleviate renal aging and injury by regulating autophagic activity and its related signaling pathways. In vivo, rats were administered with either hyperoside or VE after renal aging modeling induced by D-gal. Changes in renal aging and injury markers, autophagic activity and AMPK-ULK1 signaling pathway in the kidneys were analysed. In vitro, the NRK-52E cells exposed to D-gal were used to investigate regulative actions of hyperoside and VE on cell viability, renal tubular cellular aging markers, autophagic activity and its related signaling pathways by histomorphometry, immunohistochemistry, immunofluorescence, lentiviral transfection and Western blot. Aging and injury in the kidneys and renal tubular cells induced by D-gal were ameliorated by hyperoside and VE. Hyperoside and VE inhibited autophagic activity through mTOR-independent and AMPK-ULK1 signaling pathways. Hyperoside, as a component of phytomedicine similar to VE, attenuated renal aging and injury induced by D-gal via inhibiting AMPK-ULK1-mediated autophagy. This study provides the first evidence that hyperoside contributes to the prevention of age-associated renal injury.


Assuntos
Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Galactose/toxicidade , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Proteínas Quinases/metabolismo , Quercetina/análogos & derivados , Animais , Autofagia/efeitos dos fármacos , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Proteínas Quinases/genética , Quercetina/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
11.
Molecules ; 23(10)2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30332764

RESUMO

Flower of Abelmoschus manihot (FAM) is clinically effective to treat chronic kidney disease (CKD) with a relatively high dosage. To improve the efficacy and the compliance of patients, macroporous resins were adopted to enrich and purify flavonoids from FAM, which are thought to be the major renal protective constituents in FAM. After screening six different kinds of macroporous resins, HPD-100 was selected for its great adsorption and desorption capacity. Then, orthogonal design tests were used to optimize parameters in the processes of impurity removal and flavonoids of FAM desorption on column chromatogram. Moreover, process scale-up was performed, and purification effects maintained after amplification. After purification, the content of seven main flavonoids in the product increased from 8.29% to 51.43%. Protective and anti-inflammatory effects of crude extract and the flavonoid component of FAM after purification were investigated on the adriamycin-damaged HK-2 cells and lipopolysaccharide-stimulated Raw 264.7 cells models. Both bioactivities were improved greatly after purification for these two cell models. Therefore, the purification process had enriched the main bioactive constituents with potential alleviating kidney injury activities. The flavonoid component of FAM is worthy of being developed as an improved remedy for CKD with better patients' compliance.


Assuntos
Abelmoschus/química , Anti-Inflamatórios/isolamento & purificação , Doxorrubicina/efeitos adversos , Flavonoides/isolamento & purificação , Lipopolissacarídeos/efeitos adversos , Resinas Sintéticas/química , Adsorção , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Linhagem Celular , Flavonoides/química , Flavonoides/farmacologia , Flores/química , Humanos , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Porosidade , Células RAW 264.7
12.
Chin Med ; 13: 5, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29416556

RESUMO

Traditional Chinese medicine (TCM) is currently the best-preserved and most influential traditional medical system with the largest number of users worldwide. In recent years, the trend of TCM adoption has increased greatly, but the process of TCM internationalization has suffered from a series of setbacks for both internal and external reasons. Thus, the process of TCM internationalization faces formidable challenges, although it also has favourable opportunities. Using SWOT analysis, this paper investigates the strengths, weaknesses, opportunities and threats for TCM. These findings can serve as references for TCM enterprises with global ambitions.

13.
Artigo em Inglês | MEDLINE | ID: mdl-28620417

RESUMO

Hyperplasia of mammary glands (HMG) is common in middle-aged women. Danlu capsules (DLCs) can effectively relieve pain and improve clinical symptoms and are safe for treating HMG. However, the active substances in DLCs and the molecular mechanisms of DLCs in HMG remain unclear. This study identified the bioactive compounds and delineated the molecular targets and potential pathways of DLCs by using a systems pharmacology approach. The candidate compounds were retrieved from the traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform. Each candidate's druggability was analyzed according to its oral bioavailability and drug-likeness indices. The candidate proteins and genes were extracted in the TCMSP and UniProt Knowledgebase, respectively. The potential pathways associated with the genes were identified by performing gene enrichment analysis with DAVID Bioinformatics Resources 6.7. A total of 603 compounds were obtained from DLCs, and 39 compounds and 66 targets associated with HMG were obtained. Gene enrichment analysis yielded 10 significant pathways with 34 targets. The integrated HMG pathway revealed that DLCs probably act in patients with HMG through multiple mechanisms of anti-inflammation, analgesic effects, and hormonal regulation. This study provides novel insights into the mechanisms of DLCs in HMG, from the molecular level to the pathway level.

14.
Zhongguo Zhong Yao Za Zhi ; 41(20): 3782-3791, 2016 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-28929656

RESUMO

This research is to analyze the resourceful chemical composition in different tissues (root, stem, leaf and flower) of Abelmoschus manihot and evaluate their utilizing value. The flavonoids, soluble polysaccharides, cellulose, nucleosides and amino acids in the different tissues of A. manihot were determined by HPLC coupled with UV-Vis spectrophotpmetry, and UPLC-TQ/MS. The flowers are rich in the resourceful chemical compositions of flavonoids which mainly consist of hyperoside, isoquercitrin, cotton-8-O-glucuronide, myricetin, quercetin-3'-O-glucoside, rutin and quercetin. The total content of these flavonoids is 25.450 mg•g-1 in the flowers, while they are trace in the other tissues.Different tissues of A. manihot are rich in soluble polysaccharides and celluloses and the stems have the highest content(19.76%) of soluble polysaccharides, while the roots have the highest content (29.88%) of cellulose. Total of 21 amino acids and 9 nucleosides were detected in this plant, and the flowers have the highest content of amino acids(4.737 mg•g⁻¹), while the leaves have the highest content of nucleosides (1.474 mg•g⁻¹). A. manihot is rich in the resourceful chemical compositions, and its constituents and contents are various in different tissues of this plant.The results provided a scientific basis for the utilization and industrial development of A. manihot plants.


Assuntos
Abelmoschus/química , Flavonoides/análise , Cromatografia Líquida de Alta Pressão , Flores/química , Extratos Vegetais/química , Folhas de Planta/química , Raízes de Plantas/química , Caules de Planta/química , Plantas Medicinais/química
15.
J Ethnopharmacol ; 173: 256-65, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26226437

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM), Abelmoschus manihot (L.) medic (AM) is a natural medicinal plant used for the treatment of inflammatory diseases. Recently, Huangkui capsule (HKC), a Chinese patent medicine extracted from AM, has been widely applied to the clinical therapy of renal fibrosis in patients with early diabetic nephropathy (DN). However, the therapeutic mechanisms involved in vivo remain ambiguous. The goal of this study is to expound the mechanism in vivo of HKC in order to deepen the understanding of its clinical effects, by using the approaches of contrasting the dose-effects of HKC on oxidative stress (OS) in the kidney compared to α-lipoic acid (LA), and then demonstrating whether and how anti-oxidative properties of HKC or LA might be beneficial for the treatment of renal fibrosis in vivo. MATERIALS AND METHODS: Thirty-three rats were divided into 5 groups, a Sham group, a Vehicle group, a L-HKC group, a H-HKC group and a LA group. The different doses of HKC, LA and distilled water were daily administrated for 8 weeks after the induction of DN by the unilateral nephrectomy combined with streptozotocin (STZ) intraperitoneal injections. Rat's general status, biochemical parameters, renal histological changes and OS indicators, as well as the key protein expressions in p38 mitogen-activated protein kinase (p38MAPK)/serine-threonine kinase (Akt) signaling pathways and downstream cytokines including transforming growth factor (TGF)-ß1 and tumor necrosis factor (TNF)-α were examined, respectively. RESULTS: HKC and LA ameliorated body weight, kidney weight, urinary albumin and renal function including blood urea nitrogen and serum uric acid, attenuated renal fibrosis including the cell numbers and extracellular matrix rate in glomerulus, and controlled OS indicators including malondialdehyde, total superoxide dismutase, 8-hydroxy-2'-deoxyguanosine and nicotinamide adenine dinucleotide phosphate oxidase 4, but did not lower blood glucose in DN model rats. Among them, the anti-renal fibrosis effect of H-HKC was better than that of LA. In addition, HKC simultaneously down-regulated the protein expressions of phosphorylated p38MAPK, phosphorylated Akt (p-Akt), TGF-ß1 and TNF-α in the kidney of DN model rats, unlike HKC, LA only down-regulated p-Akt and TNF-α protein expressions. CONCLUSION: We have demonstrated that HKC, similar to LA, is renoprotective via attenuating OS and renal fibrosis in the DN rat model. The potential mechanisms by which HKC and LA exert their therapeutic effects in vivo are respectively through down-regulating the activation of p38MAPK and/or Akt pathways as well as the expressions of TGF-ß1 and/or TNF-α in the kidney. Our findings thus provide the useful information about a clinical combination of HKC and LA in early DN patients.


Assuntos
Abelmoschus , Antioxidantes/farmacologia , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Ácido Tióctico/farmacologia , Animais , Antioxidantes/uso terapêutico , Cápsulas , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/patologia , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/uso terapêutico , Fibrose , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Ácido Tióctico/uso terapêutico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
16.
Zhong Yao Cai ; 36(5): 721-5, 2013 May.
Artigo em Chinês | MEDLINE | ID: mdl-24218960

RESUMO

OBJECTIVE: To establish HPLC fingerprint of Ophiopogonis Radix of Sichuan and simultaneously determine two homoisoflavonoids (methylophiopogonanones A and B). METHODS: Full-quantified HPLC fingerprint was used to establish the HPLC fingerprint and determine the active ingredients of the daodi medicinal material Ophiopogonis Radix of Sichuan in Shengmai injection. Chromatographic condition was as follows: The analytical column was Waters symmetry shield RP 18 (4.6 mm x 250 mm, 5 microm) with a pre-column of symmetry shield RP 18. The mobile phase was acetonitrile-water (containing 0.1% phosphoric acid) with gradient elution. The flow rate was 1.0 mL/min, the detection wavelength was set at 280 nm and the column temperature was maintained at 30 degrees C. RESULTS: The HPLC fingerprint of Ophiopogonis Radix of Sichuan was established with good separation and repeatability. 24 common peaks were defined in the HPLC fingerprint. The similarity among batches was more than 0.98. Compared with standard reference substances, No. 14 peak was methylophiopogonanone A and No. 15 peak was methylophiopogonanone B. Similarity determine system was applied to evaluate them. CONCLUSION: This analytical method is highly sensitive with strong specificity, which can be used efficiently in the quality control of Ophiopogonis Radix of Sichuan in Shengmai injection.


Assuntos
Benzodioxóis/análise , Medicamentos de Ervas Chinesas/análise , Isoflavonas/análise , Ophiopogon/química , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/normas , Raízes de Plantas/química , Controle de Qualidade , Reprodutibilidade dos Testes
17.
Zhong Yao Cai ; 36(1): 132-6, 2013 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-23750421

RESUMO

OBJECTIVE: To Set up a method for determining the contents of the five flavonoids simultaneously in the HuangKui capsule and analyze their specific chromatograms. METHODS: HPLC method was used. The analytical column was Thermo scientific Hypersil GOLD (250 mm x 4.6 mm, 5 microm). The mobile phase was composed of acetonitrile (A) and 0.2% orthophosphoric acid (B) with gradient elution. The flow rate was 0.8 mL/min and detection wavelength was 360 nm. The column temperature was maintained at 30 degrees C. RESULTS: Contents of the five flavonoids (Rutin, Hyperoside, Isoquercitrin, Myricetin, Quercitrin) had good resolution with the correlation coefficients exceed 0.9999 and the average percent recovery lied in 98.46% to 100.33%. The chromatograms of the HuangKui capsule shared 15 common peaks in which 5 of them were recognized by the reference standard. Chromatograms of 10 lots of HuangKui capsule were analyzed with the similarities over 0.95. CONCLUSION: The proposed method of contents determination and chromatogram analysis has strong characteristic and specificity. This method is fast, easy and reliable, and can be applied for quality control of the preparation.


Assuntos
Abelmoschus/química , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Flavonoides/análise , Cápsulas , Medicamentos de Ervas Chinesas/normas , Controle de Qualidade , Quercetina/análogos & derivados , Quercetina/análise , Reprodutibilidade dos Testes , Rutina/análise
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