RESUMO
Angelica sinensis, commonly known as Dong Quai in Europe and America and as Dang-gui in China, is a medicinal plant widely utilized for the prevention and treatment of osteoporosis. In this study, we report the discovery of a new category of phthalide from Angelica sinensis, namely falcarinphthalides A and B (1 and 2), which contains two fragments, (3R,8S)-falcarindiol (3) and (Z)-ligustilide (4). Falcarinphthalides A and B (1 and 2) represent two unprecedented carbon skeletons of phthalide in natural products, and their antiosteoporotic activities were evaluated. The structures of 1 and 2, including their absolute configurations, were established using extensive analysis of NMR spectra, chemical derivatization, and ECD/VCD calculations. Based on LC-HR-ESI-MS analysis and DFT calculations, a production mechanism for 1 and 2 involving enzyme-catalyzed Diels-Alder/retro-Diels-Alder reactions was proposed. Falcarinphthalide A (1), the most promising lead compound, exhibits potent in vitro antiosteoporotic activity by inhibiting NF-κB and c-Fos signaling-mediated osteoclastogenesis. Moreover, the bioinspired gram-scale total synthesis of 1, guided by intensive DFT study, has paved the way for further biological investigation. The discovery and gram-scale total synthesis of falcarinphthalide A (1) provide a compelling lead compound and a novel molecular scaffold for treating osteoporosis and other metabolic bone diseases.
RESUMO
Qishen Gubiao granules, a traditional Chinese medicine preparation composed of nine herbs, have been widely used to prevent and treat coronavirus disease 2019 with good clinical efficacy. In the present study, an integrated strategy based on chemical profiling followed by network pharmacology and molecular docking was employed, to explore the active components and potential molecular mechanisms of Qishen Gubiao granules in the therapy of coronavirus disease 2019. Using the ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry technique, a total of 186 ingredients corresponding to eight structure types in Qishen Gubiao preparation were identified or structurally annotated with the elucidation of the fragmentation pathways in the typical compounds. The network pharmacology analysis screened 28 key compounds including quercetin, apigenin, scutellarein, luteolin and naringenin acting on 31 key targets, which possibly modulated signal pathways associated with immune and inflammatory responses in the treatment of coronavirus disease 2019. The molecular docking results observed that the top 5 core compounds had a high affinity for angiotensin-converting enzyme 2 and 3-chymotrypsin-like protease. This study proposed a reliable and feasible approach for elucidating the multi-components, multi-targets, and multi-pathways intervention mechanism of Qishen Gubiao granules against coronavirus disease 2019, providing a scientific basis for its further quality evaluation and clinical application.
Assuntos
COVID-19 , Medicamentos de Ervas Chinesas , Humanos , Cromatografia Líquida de Alta Pressão , Simulação de Acoplamento Molecular , Farmacologia em Rede , Medicina Tradicional Chinesa , Espectrometria de MassasRESUMO
Background: Abelmoschus manihot (L.) Medik ("Huangkui" in Chinese, HK) has been widely used for the treatment of kidney diseases. Nephrotoxicity is the side effect of cisplatin (CDDP), which greatly limits its clinical application. Therefore, CDDP could be used to establish the chronic kidney disease (CKD) model. However, the protective effects of HK on CDDP-induced CKD have not been investigated. Purpose: To explore the protective effect and underlying mechanisms of HK on multiple low-dose CDDP-induced CKD in rats by the integrated analysis of serum, kidney, and urine metabolomics and network pharmacology. Methods: The CKD model was induced by multiple low-dose CDDP. Body weight, organ index, serum biochemical, and kidney histology were examined to evaluate the effect of HK. Serum, kidney, and urine were collected and profiled by HILIC/RPLC-Q-TOF/MS-based metabolomics. Potential biomarkers (PBs) were screened according to the criteria of VIP >1, p < 0.01, and FC > 2, and then identified or assigned. The pathway analysis and PBs enrichment were conducted by MetaboAnalyst and ChemRICH. Furthermore, network pharmacology was adopted to dig out the active components and targets. Finally, the results from metabolomics and network pharmacology were integrated to confirm each other. Results: HK could recover the CDDP-induced abnormal pharmacological and metabolic profile changes. A total of 187 PBs were screened and identified from the serum, kidney, and urine metabolomics. Pathway analysis showed that multiple metabolic pathways, mainly related to amino acid and lipid metabolisms, were involved in the nephroprotective effect of HK, and especially, HK could significantly alleviate the disorder of tryptophan metabolism pathway in serum, kidney, and urine. Meanwhile, network pharmacology analysis revealed that 5 components in HK and 4 key genes could be responsible for the nephroprotection of HK, which also indicated that the metabolism of tryptophan played an important role in HK against CKD. Conclusion: HK has a nephroprotection on CDDP-induced CKD, mainly by restoring the dysregulation of tryptophan metabolism. Integrated analysis of serum, kidney, and urine metabolomics and network pharmacology was a powerful method for exploring pharmacological mechanisms and screening active components and targets of traditional Chinese medicine.
RESUMO
The relationship between folic acid and S-adenosylhomocysteine (SAH) is controversial. This study aims to explore the effect of different doses of folic acid supplementation on SAH levels in hypertensive patients and the modification of methylene-tetrahydrofolate reductase (MTHFR) C677T gene polymorphism. A randomized, double-blind, controlled clinical trial was conducted. Hypertensive patients aged 45-75 years without a history of stroke and cardiovascular disease were selected, who were randomly assigned to one of 8 dose groups. This trial has been registered with Trial Number: ChiCTR1800016135. In the total population, folic acid supplementation of 0.4-2.0â mg/day had no effect on SAH level (ßâ =â 0.47, 95% CI: -0.86-1.79, pâ =â 0.491), while folic acid supplementation of 2.4â mg/day significantly increased SAH level (ßâ =â 1.93, 95% CI: 0.22-3.64, pâ =â 0.027). Stratified analysis found that MTHFR C677T genotype CC supplemented with 2.4â mg/day folic acid had no effect on SAH level (ßâ =â 0.30, 95% CI: -2.74-3.34, pâ =â 0.847), while CT and TT genotype supplemented with 2.4â mg/day folic acid showed a significant increase in SAH level (CT: ßâ =â 2.98, 95% CI: 0.34-5.62, pâ =â 0.027; TT: ßâ =â 3.00, 95% CI: -0.51-6.51, pâ =â 0.095; CT combined with TT: ßâ =â 2.99, 95% CI: 0.90-5.09, pâ =â 0.005). In conclusion, supplementation of 2.4â mg/day folic acid can lead to increased SAH levels, especially in MTHFR C677T genotype CT and TT.
RESUMO
Aim: To investigate the efficacy and safety of adjuvant EGFR tyrosine kinase inhibitors for resected EGFR-mutated non-small-cell lung cancer. Materials & methods: Eligible phase II/III randomized controlled trials were included for the network meta-analyses (PROSPERO CRD42021275150). Results: Nine records and 831 patients were involved. Adjuvant chemotherapy followed with osimertinib significantly prolonged disease-free survival compared with chemotherapy (hazard ratio [HR]: 0.2; 95% CI: 0.14-0.29), chemotherapy followed with erlotinib (HR: 0.33; 95% CI: 0.18-0.6), chemotherapy followed with gefitinib (HR: 0.36; 95% CI: 0.16-0.82), gefitinib (HR: 0.26; 95% CI: 0.17-0.41) and icotinib (HR: 0.56; 95% CI: 0.3-0.98). Icotinib was the least likely to cause grade ≥3 adverse events. Conclusion: Chemotherapy followed with osimertinib brings about the best disease-free survival. Icotinib monotherapy shows the best safety.
Patients with early-stage non-small-cell lung cancer have about a one in five chance of cancer recurrence, even after complete resection. Using agents targeting EGFR, known as adjuvant EGFR tyrosine kinase inhibitors, after surgery is an effective way for patients with EGFR-mutated non-small-cell lung cancer to prevent recurrence. However, the optimal agent with favorable efficacy and safety is yet to be determined. This study showed that adjuvant chemotherapy followed with osimertinib had the best efficacy, while adjuvant icotinib monotherapy had the best safety.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Gefitinibe/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Metanálise em Rede , Inibidores de Proteínas Quinases/efeitos adversosRESUMO
Eleven undescribed and three known pterocarpans were isolated and identified from the traditional Chinese medicine "Huang-qi", Astragali Radix (the root of Astragalus membranaceus var. mongholicus (Bunge) P.K.Hsiao). The structures of these pterocarpans were determined using spectroscopic, X-ray crystallographic, quantum chemical calculation, and chemical methods. Pterocarpans, almost exclusively distributed in the family of Leguminosae, are the second largest subgroup of isoflavanoids. However, pterocarpan glycoside number is limited, most of which are glucosides, and only one pterocarpan apioside was isolated from nature. Notably, nine rare apiosyl-containing pterocarpan glycosides were isolated and identified. The hypoglycemic activities of all these compounds were evaluated using α-glucosidase and DPP-IV inhibitory assays respectively, and some isolates displayed the α-glucosidase inhibitory function. The antioxidant activities of all compounds were evaluated using the ORAC and DPPH radical scavenging assays, respectively. All compounds exhibited varying degrees of oxygen radical absorbance capacity, and some compounds displayed DPPH radical scavenging ability.
Assuntos
Astragalus propinquus , Pterocarpanos , Astragalus propinquus/química , Glicosídeos , Medicina Tradicional Chinesa , alfa-GlucosidasesRESUMO
Low-level laser therapy (LLLT) has been a treatment modality by many androgenetic alopecia (AGA) patients in recent years. It remained unclear as to how long the treatment regime should be maintained, and which characteristics of patients should this be recommended. A real-world study was carried out with an FDA-cleared low-level laser helmet for 1383 patients. Ordinal logistic regression analysis with propensity score matching (PSM) was used to investigate the factors related to efficacy assessment. More than 80% of users were between 18 and 40 years old. The median use times were 133 for mild AGA patients and 142 for moderate-to-severe AGA patients, which equated to 38 weeks and 40 weeks, respectively. The overall clinical effectiveness was nearly 80%. PSM analysis revealed that gender (P = 0.002), use period (P = 0.068), scalp conditions with dandruff, rash, and itchy symptoms were associated with the grading of efficacy assessment. Male users (ordinal OR: 1.35, CI: (1.01, 1.79)); use for more than 180 times or use period for 1 year (ordinal OR: 1.40, CI: (1.11, 1.96)); and those with scalp dandruff (ordinal OR: 1.34, CI: (1.01, 1.87)), rash (ordinal OR: 1.47, CI: (1.04, 2.07)), and itchy symptoms (ordinal OR: 1.51, CI: (1.12, 2.03)) had better efficacy assessments. The recommended treatment regime with low-level laser helmet was more than 1 year or 180 use times. Male patients with dandruff, rash, and itchy symptoms in scalps tended to have a better efficacy assessment.
Assuntos
Caspa , Exantema , Terapia com Luz de Baixa Intensidade , Adolescente , Adulto , Alopecia/radioterapia , Humanos , Masculino , Couro Cabeludo , Resultado do Tratamento , Adulto JovemRESUMO
Biotransformation of α-asarone by Alternaria longipes CGMCC 3.2875 yielded two pairs of new neolignans, (+) (7S, 8S, 7'S, 8'R) iso-magnosalicin (1a)/(-) (7R, 8R, 7'R, 8'S) iso-magnosalicin (1b) and (+) (7R, 8R, 7'S, 8'R) magnosalicin (2a)/(-) (7S, 8S, 7'R, 8'S) magnosalicin (2b), and four known metabolites, (±) acoraminol A (3), (±) acoraminol B (4), asaraldehyde (5), and 2, 4, 5-trimethoxybenzoic acid (6). Their structures, including absolute configurations, were determined by extensive analysis of NMR spectra, X-ray crystallography, and quantum chemical ECD calculations. The cytotoxic activity and Aß42 aggregation inhibitory activity of all the compounds were evaluated. Compound 2 displayed significant anti-Aß42 aggregation activity with an inhibitory rate of 60.81% (the positive control EGCG: 69.17%). In addition, the biotransformation pathway of α-asarone by Alternaria longipes CGMCC 3.2875 was proposed.
Assuntos
Alternaria , Lignanas , Derivados de Alilbenzenos , Anisóis , Biotransformação , Estrutura MolecularRESUMO
Importance: Overtreatment of early-stage breast cancer with favorable tumor biology in older patients may be harmful without affecting recurrence and survival. Guidelines that recommend deimplementation of sentinel lymph node biopsy (SLNB) (Choosing Wisely) and radiotherapy (RT) (National Comprehensive Cancer Network) have been published. Objective: To describe the use rates and association with disease recurrence of SLNB and RT in older women with breast cancer. Design, Setting, and Participants: This cohort study obtained patient and clinical data from an integrated cancer registry and electronic health record of a single health care system in Pennsylvania. The cohort was composed of consecutive female patients 70 years or older who were diagnosed with early-stage, estrogen receptor-positive, ERBB2 (formerly HER2)-negative, clinically node-negative breast cancer from January 1, 2010, to December 31, 2018, who were treated at 15 community and academic hospitals within the health system. Exposures: Sentinel lymph node biopsy and adjuvant RT. Main Outcomes and Measures: Primary outcomes were 5-year locoregional recurrence-free survival (LRFS) rate and disease-free survival (DFS) rate after SLNB and after RT. Secondary outcomes included recurrence rate, subgroups that may benefit from SLNB or RT, and use rate of SLNB and RT over time. Propensity scores were used to create 2 cohorts to separately evaluate the association of SLNB and RT with recurrence outcomes. Cox proportional hazards regression model was used to estimate hazard ratios (HRs). Results: From 2010 to 2018, a total of 3361 women 70 years or older (median [interquartile range {IQR}] age, 77.0 [73.0-82.0] years) with estrogen receptor-positive, ERBB2-negative, clinically node-negative breast cancer were included in the study. Of these women, 2195 (65.3%) received SLNB and 1828 (54.4%) received adjuvant RT. Rates of SLNB steadily increased (1.0% per year), a trend that persisted after the 2016 adoption of the Choosing Wisely guideline. Rates of RT decreased slightly (3.4% per year). To examine patient outcomes and maximize follow-up time, the analysis was limited to cases from 2010 to 2014, identifying 2109 patients with a median (IQR) follow-up time of 4.1 (2.5-5.7) years. In the propensity score-matched cohorts, no association was found between SLNB and either LRFS (HR, 1.26; 95% CI, 0.37-4.30; P = .71) or DFS (HR, 1.92; 95% CI, 0.86-4.32; P = .11). In addition, RT was not associated with LRFS (HR, 0.33; 95% CI, 0.09-1.24; P = .10) or DFS (HR, 0.99; 95% CI, 0.46-2.10; P = .97). Subgroup analysis showed that stratification by tumor grade or comorbidity was not associated with LRFS or DFS. Low absolute rates of recurrence were observed when comparing the groups that received SLNB (3.5%) and those that did not (4.5%) as well as the groups that received RT (2.7%) and those that did not (5.5%). Conclusions and Relevance: This study found that receipt of SLNB or RT was not associated with improved LRFS or DFS in older patients with ER-positive, clinically node-negative breast cancer. Despite limited follow-up time and wide 95% CIs, this study supports the continued deimplementation of both SLNB and RT in accordance with the Choosing Wisely and National Comprehensive Cancer Network guidelines.
Assuntos
Neoplasias da Mama/terapia , Radioterapia Adjuvante/estatística & dados numéricos , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Procedimentos Desnecessários , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Recidiva Local de Neoplasia , Avaliação de Resultados em Cuidados de Saúde , Intervalo Livre de Progressão , Receptor ErbB-2 , Receptores de Estrogênio , Sistema de Registros , Estudos RetrospectivosRESUMO
Coronavirus disease 2019 (COVID-19) pandemic is spreading rapidly around the globe. By the establishment of an integrative system combining both traditional Chinese medicine (TCM) and western medicine, China has achieved good clinical efficacy in the prevention and control of the pandemic. The advantages of TCM in the treatment of COVID-19 include effective relief of symptoms, retarding the development from mild and moderate to severe, improvement of cure rate, reducing death rates, and promotion of rehabilitation. Besides, according to the different severity levels of individual cases, the National Health Commission of the People's Republic of China issued treatment guidelines that provide corresponding prescriptions for patients. From the perspective of TCM, this review aims to analyze the role of a variety of TCM prescriptions in the treatment of COVID-19, focusing on the analysis of the "Three TCM prescriptions and three medicines" recommended by the Chinese authorities during the pandemic. We expect that this review will provide insights into the prevention and treatment of COVID-19 with TCM.
RESUMO
Pumpkins (Cucurbita moschata; Cucurbitaceae) are the rich source of nutrients and valued for their biologically active substances to be used for the treatment of several diseases. The contents, composition, and conformation of starch are the significant quality traits of C. moschata. Two germplasms were targeted for analysis regarding the taste difference. Results indicated that the total starch contents and amylose/amylopectin ratio were high in CMO-X as compared to CMO-E during each fruit development stage. Scanning electron microscopy and transmission electron microscopy observations revealed that smooth surface starch granules fused together to enhance the starch accumulation. For a comparison of fruit development in CMO-E and CMO-X, the putative pathway for starch metabolism was developed and homologs were identified for each key gene involved in the pathway. GBSS and SBE were correlated with the difference in the amylose/amylopectin ratio of CMO-E and CMO-X. Conclusively, the developmental regulation of genes associated with starch accumulation can be considered as an important factor for the determination of fruit quality.
Assuntos
Cucurbita/química , Frutas/crescimento & desenvolvimento , Extratos Vegetais/química , Amido/química , Cucurbita/crescimento & desenvolvimento , Frutas/químicaRESUMO
OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION: Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).
Assuntos
Adenina/análogos & derivados , Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos/uso terapêutico , Adenina/uso terapêutico , Adulto , Antivirais/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Antígenos E da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Humanos , Masculino , Medicina Tradicional Chinesa , Adulto JovemRESUMO
BACKGROUND: Laparoscopic Roux-en-Y gastric bypass is a leading metabolic surgery for obese patients with type 2 diabetes mellitus. However, postoperative nutritional deficiencies and abnormal bone metabolism are possible. In this study, we investigated the mid-term impact on bone metabolism of laparoscopic Roux-en-Y gastric bypass. METHODS: This retrospective study involved 238 patients with type-2 diabetes mellitus and obesity who underwent laparoscopic Roux-en-Y gastric bypass in our institution; patients were followed for 3 years. Patients received a calcium supplement (1,200 mg per day), alfacalcidol (0.5 µg per day), and a multivitamin (1 tablet per day), postoperatively. We recorded and analyzed patients' body mass index, and blood levels of 25-hydroxy-vitamin D, calcium, and parathyroid hormone. Data for 16 patients 6 months postoperatively were selected randomly to evaluate bone-specific alkaline phosphatase and the bone resorption marker, C-terminal crosslinking telopeptide of type I collagen (CTX-1). RESULTS: Of the 238 patients, 111 were women, and 127 were men (mean age: 46.91±12.03 years; mean body mass index: 31.37 kg/m2). 25-hydroxy vitamin D3 levels did not change (P>0.05) compared with preoperative levels during the 3-year follow-up. Parathyroid hormone (PTH) levels increased (P<0.05), while serum calcium decreased (P<0.05). Patients' body mass index decreased sharply 3 months postoperatively (preoperative vs. postoperative mean: 31.37±3.52 vs. 25.60±2.86, respectively; P<0.05). We saw no decrease in 25-hydroxy vitamin D3 levels with supplementation, postoperatively. CTX-1 and bone-specific alkaline phosphatase levels showed no significant changes comparing pre- and postoperative levels at 6-, 12-, and 24 months (P>0.05). However, CTX-1 levels increased in the first 12 months postoperatively, then decreased in the second year; bone alkaline phosphatase levels increased gradually. CONCLUSIONS: Laparoscopic Roux-en-Y gastric bypass is effective for weight loss, but also has an impact on bone metabolism, which increases the risk of fracture. Our results highlight the importance of regular follow-ups and full-dose calcium and vitamin supplementation, postoperatively.
RESUMO
Thermal treatment is an effective technique to modify the physiochemical properties of starch. However, investigation on the effect of repeated dry-heat treatment (RDHT) on the starch properties is limited. In this work, RDHT and continuous dry-heat treatment (CDHT) were conducted on normal maize starch. Both treatments increased pore no on the granule surface and facilitated the granule aggregation. The solubility and swelling power of normal maize starch were improved. The levels of slowly digestible starch (SDS) and resistant starch (RS)â¯+â¯SDS were increased. The structural characteristics, including crystallinity and short-range order, were impaired. The peak viscosity and thermal properties (To, Tp, Tc and ΔH) of starch paste were decreased. When comparing of CDHT samples with the same treating time, RDHT samples showed a lower crystallinity, a weaker thermal stability, a higher paste viscosity and a lower resistance to amylase. These results were useful for industrial application of thermal treatment on starch.
Assuntos
Amido/metabolismo , Zea mays/metabolismo , Amilases/metabolismo , Cristalização , Temperatura Alta , Solubilidade , Amido/química , ViscosidadeRESUMO
The present study has been designed and carried out to evaluate the potential of coptisine on diabetic nephropathy. Diabetes was induced in SD rats through one single intraperitoneal injection of streptozotocin (65 mg/kg) method, and then diabetic rats were orally administered with 25 mg/kg/day coptisine or 50 mg/kg/day coptisine for 8 weeks. Severe impairment of renal function in rats with diabetes was observed as indicated by increased urine protein excretion, kidney hypertrophy index, serum creatinine level, and blood urea nitrogen level. Oxidative stress damage was observed as indicated by increased levels of reactive oxygen species, malondialdehyde, and decreased levels of glutathione, superoxide dismutase, and catalase. However, these alterations in kidneys of rats with diabetes were alleviated by administration of coptisine. Furthermore, the expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2) and its targeted antioxidative genes heme oxygenase 1 and NADPH quinone oxidoreductase 1 in the diabetic kidneys were significantly increased after coptisine treatment. These results suggested that coptisine ameliorated oxidative renal injury in diabetic rats, and the possible mechanisms for the renoprotective effects of coptisine may be related to activation of the Nrf2 signaling pathway.
Assuntos
Berberina/análogos & derivados , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Substâncias Protetoras/uso terapêutico , Animais , Berberina/farmacologia , Berberina/uso terapêutico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Heme Oxigenase (Desciclizante)/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , NAD(P)H Desidrogenase (Quinona)/metabolismo , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including anti-proliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, ß-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.
RESUMO
Atherosclerosis mainly contributes to cardiovascular disease, a leading cause of global morbidity and mortality. Panax notoginseng saponins (PNS) are proved to therapeutically attenuate the formation of atherosclerotic lesions. According to different sapogenin, PNS are generally classified into 20(S)-protopanaxadiol saponins (PDS) and 20(S)-protopanaxatriol saponins (PTS). It was reported that PDS and PTS might exert diverse or even antagonistic bioactivities. In this study, the probable effects of PTS and PDS on atherosclerotic development were investigated and compared in ApoE-deficient mice (ApoE-/-). Male mice were gavaged daily by PNS (200 mg/kg/d), PTS (100 mg/kg/d), or PDS (100 mg/kg/d), respectively for eight weeks. The treatments of PNS and PDS, but not PTS, showed decreased atherosclerotic lesions in the entire aorta by 45.6% and 41.3%, respectively, as evaluated by an en-face method. Both PNS and PDS can improve the plaque vulnerability, as evidenced by the increased collagen fiber, increased expression of α- smooth muscle actin (α-SMA), and decreased Cluster of differentiation 14 (CD14). Additionally, PDS also inhibit the nuclear factor kappa B (NF-κB)-mediated vascular inflammation in the aorta. In conclusion, PDS, but not PTS, might mainly contribute to the anti-atherosclerosis of P. notoginseng.
Assuntos
Panax notoginseng/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Sapogeninas/química , Sapogeninas/farmacologia , Triterpenos/química , Triterpenos/farmacologia , Animais , Apolipoproteínas E/deficiência , Aterosclerose/tratamento farmacológico , Biomarcadores , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Imunofluorescência , Imuno-Histoquímica , Lipídeos/sangue , Camundongos , Camundongos Knockout , Estrutura MolecularRESUMO
This study investigated the effect of a hawthorn polyphenol extract (HPE) on ultraviolet B (UVB)-induced damage in HaCaT cells and mice. High-performance liquid chromatography/electrospray ionization tandem mass spectrometry was used to analyze the phenolic composition of HPE. The protective effects of HPE and its main components were compared in HaCaT cells. An enzyme-linked immunosorbent assay was used to detect DNA damage (8-hydroxydeoxyguanosine levels). Flow cytometry and western blotting were used to measure the extent of apoptosis and the levels of apoptosis-related proteins, respectively. Treatment with HPE or its polyphenol components inhibited the UVB-induced damage by removing an excess of reactive oxygen species (ROS), reducing DNA damage and p53 activation, regulating the protein expression of B-cell lymphoma 2 family members toward antiapoptotic ratios, and reducing caspase activation. Similar effects were observed in a UVB-irradiated mouse skin, as detected using terminal deoxynucleotidyl transferase dUTP nick-end labeling, immunohistochemistry, and western blotting assays. These results suggest that HPE can be used as a natural dietary supplement for the prevention and treatment of UVB radiation-induced skin damage. PRACTICAL APPLICATIONS: Hawthorn (Crataegus pinnatifida) shows antioxidant, anti-inflammatory, and lipid-lowering effects. As natural, healthy, and effective additives, HPEs have been widely used in food and health products. The results of this study reveal the molecular mechanisms underlying HPE effects, showing that HPE reverses the effects of UVB irradiation via removal of an excess of ROS and reduction of DNA damage and p53 expression in vitro and in vivo. Consequently, HPE upregulates the expression of antiapoptotic BCL-2 and downregulates that of proapoptotic BAX, thereby reducing the activation of caspase-3/9 and inhibiting apoptosis. These findings suggest that HPE can be used as the base ingredient for antiphotoaging food products. This study provides both theoretical and experimental background for hawthorn deep processing and utilization.
Assuntos
Crataegus/química , Mitocôndrias/metabolismo , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Envelhecimento da Pele/efeitos da radiação , Proteína Supressora de Tumor p53/metabolismo , Animais , Apoptose/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Feminino , Frutas/química , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Mitocôndrias/efeitos da radiação , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Envelhecimento da Pele/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Raios Ultravioleta/efeitos adversosRESUMO
Five new phthalide derivatives, biscogniphthalides A-D (1, 2, 3a/3b, and 4), were isolated from Biscogniauxia sp. (No. 69-8-7-1), along with one related known phthalide (5). Their structures were determined by comprehensive spectroscopic analyses, chemical derivatization, and quantum chemical ECD calculations. In addition, the anti-acetyl cholinesterase, antimicrobial, and anti-α-glucosidase activities of 1-5 were evaluated.
Assuntos
Benzofuranos/farmacologia , Xylariales/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Benzofuranos/isolamento & purificação , China , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Estrutura MolecularRESUMO
BACKGROUND: The present study was conducted to explore the efficacy of using a free posterior tibial artery perforator flap (FPTAPF) for trachea reconstruction after resection of well-differentiated thyroid carcinoma (WDTC) invading the trachea. METHODS: We retrospectively collected and analyzed clinical and surgical data from 14 patients who underwent tracheal reconstruction using a FPTAPF after resection of WDTC invading the trachea between August 2014 and July 2017. RESULTS: Satisfactory tracheal structure and functional recovery were obtained in 11 of the 14 patients. One patient had breathing difficulties after tracheostomy closure tests because of bilateral recurrent laryngeal nerve damage caused by disease invasion. Tracheostomy incision was not closed in 2 patients because they received postoperative adjuvant radioactive iodine 131 treatment. CONCLUSION: Satisfactory tracheal reconstruction results were achieved in patients with resection of WDTC invading the trachea, indicating that a FPTAPF is a safe and reliable choice for management.