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1.
J Gastrointest Oncol ; 15(3): 1050-1059, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38989411

RESUMEN

Background: Pre-operative chemoradiation for rectal cancer is often associated with severe gastrointestinal (GI) toxicity which can interrupt, delay, and/or lead to termination of treatment. In this study, we evaluated whether the addition of YIV-906, a novel herbal medicine proven to reduce GI toxicity associated with chemotherapy could also reduce GI side effects during standard pre-operative capecitabine and pelvic radiation therapy (RT) in the neoadjuvant setting for the treatment of locally advanced rectal cancer. Methods: This single arm clinical study enrolled 24 patients between Dec 23, 2014-Sep 17, 2018 at Smilow Cancer Hospital, a comprehensive cancer center at Yale New Haven Hospital. All patients were age ≥18 years, Eastern Cooperative Oncology Group 0-1 and with histologically confirmed T3-T4 and N0-N2, M0 adenocarcinoma of the rectum. Median follow-up was 61.9 months. All patients received concurrent pelvic external beam RT (50.4 Gy in 28 fractions), YIV-906 (taken orally 800 mg twice daily on days 1-4 of RT each week), and oral capecitabine delivered in a neo-adjuvant fashion, followed by definitive surgery. Toxicity was assessed weekly during radiation and until acute symptoms resolved and then at 28 days, 4 months, 7 months and 10 months. Toxicities were graded in accordance with Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results: At the time of surgery, 4 patients (16.7%) had a complete or near-complete response. At a median follow-up of 61.9 months, the mean overall survival (OS) of our patient cohort was 74.9 months [95% confidence interval (CI): 67.3-82.5]. The estimated 5-year OS was 82.0%. We observed 0% acute grade 4 toxicities, and only two cases of acute grade 3 diarrhea (8.3%). Conclusions: The addition of YIV-906 to capecitabine based chemoradiation for locally advanced rectal cancer led to reduced rates of GI toxicity compared to historical controls, in particular grade 3 or greater diarrhea. These findings suggest YIV-906 should be evaluated in a randomized clinical trial to further assess potential reductions in the toxicity profile of chemoradiation for GI cancers.

2.
Sci Rep ; 14(1): 14330, 2024 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-38906945

RESUMEN

This study aimed to investigate the association between obesity and herpes zoster (HZ) occurrence. This study used data covering 2 million people in Taiwan in 2000, which were obtained from the National Health Insurance Research Database. The cohort study observed aged 20-100 years with obesity from 2000 to 2017 (tracking to 2018). Obesity was indicated by the presence of two or more outpatient diagnoses or at least one admission record. And, obesity was categorized into non-morbid obesity and morbid obesity. Patients with HZ before the index date were excluded. The obesity cohort and control cohort were matched 1:1 according to age, sex, comorbidities, and index year. There were 18,855 patients in both the obesity and control cohorts. The obesity cohort [adjusted hazard ratio (aHR) 1.09] had a higher risk of HZ than the control cohort. Further analysis, the morbid obesity group (aHR 1.47), had a significantly higher risk of HZ than the non-morbid obesity group. Among the patients without any comorbidities, the patients with obesity had a significantly higher risk of developing HZ than the patients without obesity (aHR 1.18). Obese patients are at a higher risk of HZ development, especially in the patients with morbid obesity. Weight reduction is critical for preventing the onset of chronic diseases and decreasing the risk of HZ in patients with obesity.


Asunto(s)
Herpes Zóster , Obesidad Mórbida , Humanos , Herpes Zóster/epidemiología , Herpes Zóster/complicaciones , Masculino , Femenino , Obesidad Mórbida/complicaciones , Obesidad Mórbida/epidemiología , Persona de Mediana Edad , Anciano , Adulto , Taiwán/epidemiología , Factores de Riesgo , Anciano de 80 o más Años , Comorbilidad , Adulto Joven , Estudios de Cohortes , Obesidad/complicaciones , Obesidad/epidemiología
4.
Eur J Med Res ; 28(1): 550, 2023 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-38042817

RESUMEN

BACKGROUND: Disease-related stress can trigger the occurrence of herpes zoster (HZ). Fatty liver disease (FLD) can have adverse effects on the human body and may induce stress in affected individuals. In this study, we investigated whether FLD is associated with an elevated risk of HZ. METHODS: For this study, we utilized data from the National Health Insurance Research Database, patients with FLD from 2000 to 2017 were observed (follow-up until 2018). Patients were considered to have FLD if they had at least two outpatient visits or at least one admission record with a diagnostic code of FLD. Patients with FLD were matched 1:1 by age, sex, comorbidities, and index year with control patients. Additionally, the FLD was further categorized into non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) groups. Multivariable Cox proportional hazards model was used to calculate the incidence rate and adjusted hazard ratio (aHR) of HZ for FLD and AFLD and for various age groups, sex and comorbidities. Cumulative incidence curve for HZ was plotted through the Kaplan-Meier method, and p-value was calculated using the log-rank test. RESULTS: After 1:1 propensity-score matching, each cohort comprised 62,418 patients. The FLD cohort was further divided into NAFLD and AFLD groups, which respectively comprised 55,709 and 6709 patients. The FLD cohort had a risk of HZ significantly higher than that of the control cohort (aHR = 1.06; p < 0.001). Additionally, the NAFLD group exhibited a significantly higher risk of HZ than did the AFLD group (aHR = 1.22; p < 0.001). Among patients without any comorbidities, those with FLD had a higher risk of HZ than did those without FLD (aHR = 1.14; p < 0.001). CONCLUSION: Patients with FLD are at an increased risk of HZ development. Additionally, NAFLD is associated with a higher risk of HZ than AFLD. Therefore, patients with NAFLD should be informed of their increased risk of HZ.


Asunto(s)
Hígado Graso Alcohólico , Herpes Zóster , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Hígado Graso Alcohólico/complicaciones , Hígado Graso Alcohólico/epidemiología , Comorbilidad , Herpes Zóster/complicaciones , Herpes Zóster/epidemiología , Factores de Edad , Factores de Riesgo
5.
Front Pharmacol ; 14: 1244655, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37860121

RESUMEN

Introduction: Prostate cancer is the second leading cause of cancer death among men in the United States. Castration-Resistant Prostate Cancer (CRPC) often develops resistance to androgen deprivation therapy. Resistance in CRPC is often driven by AR variants and glucocorticoid receptor (GR). Thus, drugs that target both could be vital in overcoming resistance. Methods: Utilizing the STAR Drug Discovery Platform, three hundred medicinal plant extracts were examined across 25 signaling pathways to identify potential drug candidates. Effects of the botanical drug YIV-818-A, derived from optimized water extracts of Rubia cordifolia (R.C.), on Dihydrotestosterone (DHT) or Dexamethasone (DEX) induced luciferase activity were assessed in 22RV1 cells harboring the ARE luciferase reporter. Furthermore, the key active compounds in YIV-818-A were identified through activity guided purification. The inhibitory effects of YIV-818-A, RA-V, and RA-VII on AR and GR activities, their impact on AR target genes, and their roles in modifying epigenetic status were investigated. Finally, the synergistic effects of these compounds with established CRPC drugs were evaluated both in vitro and in vivo. Results: YIV-818-A was found to effectively inhibit DHT or DEX induced luciferase activity in 22RV1 cells. Deoxybouvardin (RA-V) was identified as the key active compound responsible for inhibiting AR and GR activities. Both YIV-818-A and RA-V, along with RA-VII, effectively downregulated AR and AR-V proteins through inhibiting protein synthesis, impacted the expression of AR target genes, and modified the epigenetic status by reducing levels of Bromodomain and Extra-Terminal proteins (Brd2/Brd4) and H3K27Ac. Furthermore, these compounds exhibited synergistic effects with apalutamide, darolutamide, or enzalutamide, and suppressed AR mediated luciferase activity of 22RV1 cells. Co-administration of YIV-818-A and enzalutamide led to a significant reduction of 22RV1 tumor growth in vivo. Different sources of R.C. had variable levels of RA-V, correlating with their potency in AR inhibition. Discussion: YIV-818-A, RA-V, and RA-VII show considerable promise in addressing drug resistance in CRPC by targeting both AR protein and GR function, along with modulation of vital epigenetic markers. Given the established safety profile of YIV-818-A, these findings suggest its potential as a chemopreventive agent and a robust anti-prostate cancer drug.

7.
Acta Pharmacol Sin ; 44(8): 1637-1648, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36882503

RESUMEN

Hepatitis C virus (HCV) infection is one of the major factors to trigger a sustained hepatic inflammatory response and hence hepatocellular carcinoma (HCC), but direct-acting-antiviral (DAAs) was not efficient to suppress HCC development. Heat shock protein 90 kDa (HSP90) is highly abundant in different types of cancers, and especially controls protein translation, endoplasmic reticulum stress, and viral replication. In this study we investigated the correlation between the expression levels of HSP90 isoforms and inflammatory response marker NLRP3 in different types of HCC patients as well as the effect of a natural product celastrol in suppression of HCV translation and associated inflammatory response in vivo. We identified that the expression level of HSP90ß isoform was correlated with that of NLRP3 in the liver tissues of HCV positive HCC patients (R2 = 0.3867, P < 0.0101), but not in hepatitis B virus-associated HCC or cirrhosis patients. We demonstrated that celastrol (3, 10, 30 µM) dose-dependently suppressed the ATPase activity of both HSP90α and HSP90ß, while its anti-HCV activity was dependent on the Ala47 residue in the ATPase pocket of HSP90ß. Celastrol (200 nM) halted HCV internal ribosomal entry site (IRES)-mediated translation at the initial step by disrupting the association between HSP90ß and 4EBP1. The inhibitory activity of celastrol on HCV RNA-dependent RNA polymerase (RdRp)-triggered inflammatory response also depended on the Ala47 residue of HSP90ß. Intravenous injection of adenovirus expressing HCV NS5B (pAde-NS5B) in mice induced severe hepatic inflammatory response characterized by significantly increased infiltration of immune cells and hepatic expression level of Nlrp3, which was dose-dependently ameliorated by pretreatment with celastrol (0.2, 0.5 mg/kg, i.p.). This study reveals a fundamental role of HSP90ß in governing HCV IRES-mediated translation as well as hepatic inflammation, and celastrol as a novel inhibitor of HCV translation and associated inflammation by specifically targeting HSP90ß, which could be developed as a lead for the treatment of HSP90ß positive HCV-associated HCC.


Asunto(s)
Carcinoma Hepatocelular , Hepatitis C , Neoplasias Hepáticas , Ratones , Animales , Hepacivirus , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Proteínas de Choque Térmico , Proteína con Dominio Pirina 3 de la Familia NLR , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Proteínas HSP90 de Choque Térmico/metabolismo , Inflamación/tratamiento farmacológico
8.
Artículo en Inglés | MEDLINE | ID: mdl-36768020

RESUMEN

BACKGROUND: Pulmonary tuberculosis (TB), a global health problem, is typically caused by the bacterium Mycobacterium tuberculosis. Herpes zoster (HZ) is caused by the reactivation of the varicella-zoster virus (VZV). The reactivation of VZV can be caused by stress. We investigated whether pulmonary TB increases the risk of HZ development. METHODS: This study used data that sampled a population of 2 million people in 2000 from the National Health Insurance Research Database. This cohort study observed Taiwanese patients aged 20-100 years with pulmonary TB from 2000 to 2017 (tracked to 2018). Pulmonary TB was defined as having two or more outpatient diagnoses or at least one admission record. To address potential bias caused by confounding factors, the control cohort and pulmonary TB cohort were matched 1:1 by age, gender, index year, and comorbidities. Patients with HZ before the index date were excluded. RESULTS: A total of 30,805 patients were in the pulmonary TB and control cohorts. The incidence rate of HZ in pulmonary TB and control cohorts were 12.00 and 9.66 per 1000 person-years, respectively. The risk of HZ in the pulmonary TB cohort (adjusted hazard ratios = 1.23; 95% confidence interval = 1.16-1.30) was significantly higher than that of in control cohort. Among patients without comorbidities, the patients with TB were 1.28-fold more likely to have HZ than those without TB. CONCLUSION: Patients with TB should be well treated to avoid the potential risk of HZ occurrence. Although we identified the association between pulmonary TB and HZ, further studies are needed to confirm the result.


Asunto(s)
Herpes Zóster , Mycobacterium tuberculosis , Tuberculosis Pulmonar , Humanos , Herpesvirus Humano 3 , Estudios de Cohortes , Herpes Zóster/epidemiología , Comorbilidad , Tuberculosis Pulmonar/epidemiología , Incidencia , Factores de Riesgo , Estudios Retrospectivos
9.
Pharmacol Res ; 187: 106625, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36563870

RESUMEN

Increasing evidence suggests that the failure of clinical antidepressants may be related with neuroinflammation. The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is an intracellular multiprotein complex, and has been considered as a key contributor to the development of neuroinflammation. Inhibition of NLRP3 inflammasome is an effective method for depression treatment. In this review, we summarized current researches highlighting the role of NLRP3 inflammasome in the pathology of depression. Firstly, we discussed NLRP3 inflammasome activation in patients with depression and animal models. Secondly, we outlined the possible mechanisms driving the activation of NLRP3 inflammasome. Thirdly, we discussed the pathogenetic role of NLRP3 inflammasome in depression. Finally, we overviewed the current and potential antidepressants targeting the NLRP3 inflammasome. Overall, the inhibition of NLRP3 inflammasome activation may be a potential therapeutic strategy for inflammation-related depression.


Asunto(s)
Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Depresión/tratamiento farmacológico , Enfermedades Neuroinflamatorias , Antidepresivos/uso terapéutico , Antidepresivos/farmacología
11.
Food Sci Nutr ; 10(12): 4270-4295, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36514751

RESUMEN

Ziziphus jujuba Mill is the dried ripe fruit of the Rhamnaceae family; it is widely distributed in Shandong, Henan, Liaoning, and other places in China. In folk medicine, it was used to restore vital energy, as a blood tonic, and for the treatment of spleen deficiency. To date, a complete investigation of the compounds of Z. jujuba has rarely been performed. Therefore, a reliable strategy based on UHPLC-Q-Exactive Orbitrap MS, combined with trace data acquisition mode (parallel reaction monitoring scanning, PRM) and multiple data processing methods, is necessary for the characterization of compounds in the Z. jujuba. Ultimately, 295 compounds, including 69 flavonoids, 60 alkaloids, 82 phenylpropanoids, 52 organic acids, and 32 other components, were identified in the Z. jujuba; of these, 270 have been reported in Z. jujuba for the first time. This study provides deep insights into the chemistry of Z. jujuba and could be useful for further studies aimed at identifying the factors contributing to the health benefits attributed to this fruit.

12.
BMC Musculoskelet Disord ; 23(1): 961, 2022 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-36348331

RESUMEN

BACKGROUND: The reactivation of herpes zoster (HZ) is associated with disease stress. However, the relationship between chondromalacia patella (CMP) and HZ remains poorly understood. This study investigated the relationship between CMP and the risk of developing HZ. METHODS: Data were collected from the Taiwan's National Health Insurance Research Database. Patients with CMP diagnosed between 2000 and 2017 were assigned to the case group; patients without CMP were randomly selected from the same database and paired with controls matched by age and sex. The primary outcome was a diagnosis of HZ. All patients were followed until their diagnosis of HZ, their withdrawal from the NHI program, their death, or the end of 2017, whichever was earliest. The risk of developing HZ was compared between the case and control groups. RESULTS: In total, 22,710 patients with CMP and 90,840 matched controls were enrolled. The overall incidence rates of HZ in the CMP and control cohorts were 7.94 and 7.35 per 1,000 person-years, respectively. After potential confounders were controlled for, the case group exhibited a higher risk of HZ than did the control group [adjusted hazard ratio (aHR) = 1.06, p < 0.05]. In a stratification analysis by age, patients over 65 years old in the CMP group exhibited a higher risk of HZ than did those in the control group (aHR = 1.22, p < 0.01). In a stratification analysis by sex, women with CMP were at greater risk of developing HZ than women without CMP (aHR = 1.18, p < 0.01). CONCLUSION: Patients with CMP, especially elder adults and women, exhibited a higher risk of HZ. The HZ risk of patients with CMP should thus be assessed, and the necessity of HZ vaccination should be informed.


Asunto(s)
Enfermedades de los Cartílagos , Herpes Zóster , Adulto , Anciano , Femenino , Humanos , Herpes Zóster/epidemiología , Herpes Zóster/complicaciones , Incidencia , Rótula , Estudios Retrospectivos , Factores de Riesgo
13.
Front Pharmacol ; 13: 816029, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35250565

RESUMEN

Ethnopharmacological evidence: In Taiwan, herbal tea is considered a traditional medicine and has been consumed for hundreds of years. In contrast to regular tea, herbal teas are prepared using plants other than the regular tea plant, Camellia sinensis (L.) Kuntze. Bitter tea (kǔ-chá), a series of herbal teas prepared in response to common diseases in Taiwan, is often made from local Taiwanese plants. However, the raw materials and formulations have been kept secret and verbally passed down by store owners across generations without a fixed recipe, and the constituent plant materials have not been disclosed. Aim of the study: The aim was to determine the herbal composition of bitter tea sold in Taiwan, which can facilitate further studies on pharmacological applications and conserve cultural resources. Materials and methods: Interviews were conducted through a semi-structured questionnaire. The surveyed respondents were traditional sellers of traditional herbal tea. The relevant literature was collated for a systematic analysis of the composition, characteristics, and traditional and modern applications of the plant materials used in bitter tea. We also conducted an association analysis of the composition of Taiwanese bitter tea with green herb tea (qing-cao-cha tea), another commonly consumed herbal tea in Taiwan, as well as herbal teas in neighboring areas outside Taiwan. Results: After visiting a total of 59 stores, we identified 32 bitter tea formulations and 73 plant materials. Asteraceae was the most commonly used family, and most stores used whole plants. According to a network analysis of nine plant materials used in high frequency as drug pairs, Tithonia diversifolia and Ajuga nipponensis were found to be the core plant materials used in Taiwanese bitter tea. Conclusion: Plant materials used in Taiwanese bitter tea were distinct, with multiple therapeutic functions. Further research is required to clarify their efficacy and mechanisms.

14.
Artículo en Inglés | MEDLINE | ID: mdl-35270787

RESUMEN

Background: The association between polycystic ovary syndrome (PCOS) and the risk of herpes zoster (HZ) remains unclear. This study investigated the risk of HZ in women with PCOS. Methods: This study used data from the Longitudinal Generation Tracking Database (LGTD 2005) which contains the information of 2 million randomly selected from National Health Insurance beneficiaries. Patients who received a diagnosis of PCOS between 2000 and 2017 were included in the PCOS cohort. Patients who were not diagnosed as having PCOS were randomly selected from the LGTD 2005 and included in the control cohort. Patients who were aged <20 years and had a history of HZ before the index date were excluded. Patients who were in both the cohorts were matched at a ratio of 1:1 through propensity score matching based on age, comorbidities, and medication. The primary outcome was the diagnosis of HZ. Results: A total of 20,142 patients were included in each case and control cohorts. The incidence rates of HZ in the PCOS and control cohorts were 3.92 and 3.17 per 1000 person-years, respectively. The PCOS cohort had a significantly higher risk of HZ than did the control cohort (adjusted hazard ratios [aHR] = 1.26). Among the patients aged 30−39 years, those with PCOS had a significantly higher risk of HZ than did those without PCOS (aHR = 1.31). Among the patients without any comorbidities, those with PCOS had a significantly higher risk of HZ (aHR = 1.26) than did those without PCOS. Conclusion: PCOS is associated with the risk of HZ, especially in young women. The risk of HZ should be addressed while treating patients with PCOS. An HZ vaccine is recommended for these patients.


Asunto(s)
Herpes Zóster , Síndrome del Ovario Poliquístico , Femenino , Herpes Zóster/complicaciones , Herpes Zóster/epidemiología , Humanos , Incidencia , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/epidemiología , Estudios Retrospectivos , Factores de Riesgo
15.
Front Pharmacol ; 13: 873011, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35355733

RESUMEN

[This corrects the article DOI: 10.3389/fphar.2021.681190.].

16.
Front Pharmacol ; 13: 1095186, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36686648

RESUMEN

YIV-906 is a systems biology botanical cancer drug, inspired by a traditional Chinese herbal formulation. Results from eight Phase I/II to II clinical studies demonstrated the potential of YIV-906 to prolong survival and improve the quality of life of cancer patients. As an immunomodulator in the tumor microenvironment, YIV-906 can turn cold tumors hot and potentiate anti-tumor activity for different classes of anticancer agents; and as a cytoprotector in the GI, YIV-906 can reduce non-hematological side effects and speed up damaged tissue recovery. YIV-906 enhanced anti-PD1 action against hepatoma in mice by stimulating both innate and adaptive immunity. In a Jurkat cell-staphylococcal superantigen E (SEE)-Raji cell culture model, YIV-906 promoted T cell activation with upregulation of CD69 by enhancing NFAT activity, with or without PD1-PD-L1 interaction. YIV-906 could trigger the phosphorylation of TCR downstream signaling cascades without the involvement of TCR. YIV-906 could inhibit SHP1 and SHP2 activities, which dephosphorylates TCR downstream proteins due to the PD1-PD-L1 interaction. Therefore, YIV-906 could enhance anti-PD1 action to rescue the depressed NFAT activity of Jurkat cells due to the PD1-PD-L1 interaction. In addition, YIV-906 enhanced the NFAT activity and killing capability of Jurkat cells expressing chimeric antigen receptor (CAR-CD19-CD3z) toward CD19 expressing cells, such as Raji cells, with or without PD1-PD-L1 overexpression. Ingredient herb S (Scutellaria baicalensis Georgi) of YIV-906 and some S compounds were found to play key roles in these activities. In conclusion, YIV-906 modulates adaptive immunity by activating T effector cells mainly through its action on SHP1/2. YIV-906 could also facilitate immune checkpoint blockade therapy or CAR-T cell therapy for cancer treatment.

17.
Front Pharmacol ; 13: 1042756, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36793921

RESUMEN

Introduction: Cytochrome P450 (CYP) 3A4 is a major drug metabolizing enzyme for corticosteroids (CS). Epimedium has been used for asthma and variety of inflammatory conditions with or without CS. It is unknown whether epimedium has an effect on CYP 3A4 and how it interacts with CS. We sought to determine the effects of epimedium on CYP3A4 and whether it affects the anti-inflammatory function of CS and identify the active compound responsible for this effect. Methods: The effect of epimedium on CYP3A4 activity was evaluated using the Vivid CYP high-throughput screening kit. CYP3A4 mRNA expression was determined in human hepatocyte carcinoma (HepG2) cells with or without epimedium, dexamethasone, rifampin, and ketoconazole. TNF-α levels were determined following co-culture of epimedium with dexamethasone in a murine macrophage cell line (Raw 264.7). Active compound (s) derived from epimedium were tested on IL-8 and TNF-α production with or without corticosteroid, on CYP3A4 function and binding affinity. Results: Epimedium inhibited CYP3A4 activity in a dose-dependent manner. Dexamethasone enhanced the expression of CYP3A4 mRNA, while epimedium inhibited the expression of CYP3A4 mRNA and further suppressed dexamethasone enhancement of CYP3A4 mRNA expression in HepG2 cells (p < 0.05). Epimedium and dexamethasone synergistically suppressed TNF-α production by RAW cells (p < 0.001). Eleven epimedium compounds were screened by TCMSP. Among the compounds identified and tested only kaempferol significantly inhibited IL-8 production in a dose dependent manner without any cell cytotoxicity (p < 0.01). Kaempferol in combination with dexamethasone showed complete elimination of TNF-α production (p < 0.001). Furthermore, kaempferol showed a dose dependent inhibition of CYP3A4 activity. Computer docking analysis showed that kaempferol significantly inhibited the catalytic activity of CYP3A4 with a binding affinity of -44.73kJ/mol. Discussion: Inhibition of CYP3A4 function by epimedium and its active compound kaempferol leads to enhancement of CS anti-inflammatory effect.

18.
Adv Drug Deliv Rev ; 178: 113964, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34499982

RESUMEN

Traditional herbal medicine (THM), an ancient science, is a gift from nature. For thousands of years, it has helped humans fight diseases and protect life, health, and reproduction. Nanomedicine, a newer discipline has evolved from exploitation of the unique nanoscale morphology and is widely used in diagnosis, imaging, drug delivery, and other biomedical fields. Although THM and nanomedicine differ greatly in time span and discipline dimensions, they are closely related and are even evolving toward integration and convergence. This review begins with the history and latest research progress of THM and nanomedicine, expounding their respective developmental trajectory. It then discusses the overlapping connectivity and relevance of the two fields, including nanoaggregates generated in herbal medicine decoctions, the application of nanotechnology in the delivery and treatment of natural active ingredients, and the influence of physiological regulatory capability of THM on the in vivo fate of nanoparticles. Finally, future development trends, challenges, and research directions are discussed.


Asunto(s)
Productos Biológicos/uso terapéutico , Medicina de Hierbas , Nanomedicina , Productos Biológicos/química , Humanos
19.
Sci Rep ; 11(1): 13482, 2021 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-34188068

RESUMEN

YIV-906 (PHY906) is a standardized botanical cancer drug candidate developed with a systems biology approach-inspired by a traditional Chinese herbal formulation, historically used to treat gastrointestinal symptoms including diarrhea, nausea and vomiting. In combination with chemotherapy and/or radiation therapy, preclinical and clinical results suggest that YIV-906 has the potential to prolong survival and improve quality of life for cancer patients. Here, we demonstrated that YIV-906 plus anti-PD1 could eradicate all Hepa 1-6 tumors in all tumor bearing mice. YIV-906 was found to have multiple mechanisms of action to enhance adaptive and innate immunity. In combination, YIV-906 reduced PD1 or counteracted PD-L1 induction caused by anti-PD1 which led to higher T-cell activation gene expression of the tumor. In addition, YIV-906 could reduce immune tolerance by modulating IDO activity and reducing monocytic MDSC of the tumor. The combination of anti-PD1 and YIV-906 generated acute inflammation in the tumor microenvironment with more M1-like macrophages. YIV-906 could potentiate the action of interferon gamma (IFNg) to increase M1-like macrophage polarization while inhibiting IL4 action to decrease M2 macrophage polarization. Flavonoids from YIV-906 were responsible for modulating IDO activity and potentiating IFNg action in M1-like macrophage polarization. In conclusion, YIV-906 could act as an immunomodulator and enhance the innate and adaptive immune response and potentiate anti-tumor activity for immunotherapies to treat cancer.


Asunto(s)
Inmunidad Adaptativa/efectos de los fármacos , Carcinoma Hepatocelular/inmunología , Medicamentos Herbarios Chinos/farmacología , Inmunidad Innata/efectos de los fármacos , Neoplasias Hepáticas/inmunología , Proteínas de Neoplasias/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Microambiente Tumoral/efectos de los fármacos , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular Tumoral , Femenino , Neoplasias Hepáticas/dietoterapia , Ratones , Proteínas de Neoplasias/inmunología , Receptor de Muerte Celular Programada 1/inmunología , Microambiente Tumoral/inmunología
20.
Front Pharmacol ; 12: 681190, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35222004

RESUMEN

Kinmen is an outlying island that has the richest plant resources in Taiwan. The objective of this study was to record the methods that people in Kinmen use medicinal plants and to analyze the cultural characteristics of their use. Field investigations were carried out in various towns and villages in Kinmen, and 80 respondents were included in the survey. The search for respondents was conducted through local elderly people and medicinal plant groups. Semi-structured interviews were conducted with the local people to obtain their knowledge of medicinal plants and how they disseminate this information. Informed consent was obtained prior to the interviews, and the following was determined: plant use value (UV), frequency of citation (FC), and factor of informant consensus (Fic). These parameters were used to quantify the data and measure the agreement among the respondents on using plants to treat different diseases. Finally, the survey results were compared with the representative ethnobotanical literature in neighboring areas to evaluate the similarity between plant usage in Kinmen and neighboring areas as well as to determine whether there are new species or novel usages in the study area. In the Kinmen area, phytotherapy is generally used by elderly people with low educational attainments. According to the survey results, 83 medicinal plants belonging to 48 families were collected. These medicinal plants were mainly distributed in the Compositae, Lamiaceae, and Solanaceae families. Eighteen novel uses that have not been previously documented were found, four of which were related to newly recorded medicinal plant species in the Kinmen area. The results showed that 93.98 and 65.06% of the species collected in the present study were also recorded in literature from Taiwan and Fujian, respectively. This study showed that Kinmen's ethnobotanical knowledge is closely related to the Catalogue of Medicinal Plant Resources in Taiwan, and local people indeed shared similar uses of medicinal species with people in Taiwan and Fujian (46.99%). The results from this study highlighted the importance of traditional medicine in the Kinmen area, where people have a specific understanding of using medicinal plants and communication with people in Taiwan and Fujian Province in China. It was found that Kinmen shares ethnobotanical knowledge with Taiwan and Fujian.

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