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Network pharmacology and experimental investigation of Rhizoma polygonati extract targeted kinase with herbzyme activity for potent drug delivery.
Xie, Y, Mu, C, Kazybay, B, Sun, Q, Kutzhanova, A, Nazarbek, G, Xu, N, Nurtay, L, Wang, Q, Amin, A, et al
Drug delivery. 2021;(1):2187-2197
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Abstract
Rhizoma polygonati (Huangjing, RP) has been used for a long history with many chemical components in inducing anti-cancer, anti-aging, anti-diabetes, anti-fatigue, and more prevention of diseases or acts as nutrition sources in food. Here we investigated RP extract combination with kinase inhibitors in anti-cell growth and blockade in pathways targeting kinases. Experimental investigation and network pharmacology analysis were applied to test the potent kinase-mediated signaling. Herbzyme activity was determined by substrate with optical density measurement. Extract of processed RP inhibits cell growth in a much greater manner than alone when applied in combination with inhibitors of mTOR or EGFR. Moreover, processing methods of RP from Mount Tai (RP-Mount Tai) play essential roles in herbzyme activity of phosphatase suggesting the interface is also essential, in addition to the chemical component. The network pharmacology analysis showed the chemical component and target networks involving AKT and mTOR, which is consistent with experimental validation. Finally, EGFR inhibitor could be associated with nano-extract of RP-Mount Tai but not significantly affects the phosphatase herbzyme activity in vitro. Thus the processed extract of RP-Mount Tai may play a dual role in the inhibition of cell proliferation signaling by both chemical component and nanoscale herbzyme of phosphatase activity to inhibit kinases including mTOR/AKT in potent drug delivery of kinase inhibitors.
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Evidence of Astragalus injection combined platinum-based chemotherapy in advanced nonsmall cell lung cancer patients: A systematic review and meta-analysis.
Cao, A, He, H, Wang, Q, Li, L, An, Y, Zhou, X
Medicine. 2019;(11):e14798
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Abstract
BACKGROUND Platinum-based chemotherapy is one of the standard treatments for advanced nonsmall cell lung cancer (NSCLC). Despite on an effective treatment for advanced NSCLC patients, its high toxicity and limited clinical effects have raised big concerns. Astragalus injection (AGI) has been commonly employed as an adjutant chemotherapy drug for NSCLC in China. This review was conducted to evaluate the beneficial of AGI in combination with platinum-based chemotherapy in advanced NSCLC. METHODS We collected all studies about AGI plus platinum-based chemotherapy for advanced NSCLC in the PubMed, EMBASE, China National Knowledge Infrastructure Database, the Cochrane Library, Wanfang Database, China Biological Medicine Database, and Chinese Scientific Journal Database established on July 2018 without language restriction. Cochrane handbook was applied to assess the quality of included trials. Stata (version 12.0) and RevMan (version 5.3) were employed for data analysis. The quality of the evidence was assessed with the GRADE approach. RESULTS Nineteen randomized controlled trials (RCTs) including 1635 patients were included to determine the effectiveness and safety of AGI combined with platinum-based chemotherapy in the treatment of NSCLC. The result of meta-analysis indicated that comparing with chemotherapy alone, AGI combined chemotherapy could significantly improve the objective response rate (relative risk [RR] = 1.19, 95% confidence interval [CI] [1.06, 1.33], P = .002), the Karnofsky performance status (RR = 2.28, 95% CI [1.63, 3.18], P < .00001), and 1-year survival rate (RR = 1.40, 95% CI [1.16, 1.70], P = .0005), meanwhile increase the percentages of CD3 (weighted mean differences [WMD] = 11.98, 95% CI [8.0, 15.96], P < .00001), CD4 (WMD = 2.98, 95% CI [0.45, 5.52], P = .02), CD4/CD8 (WMD = 0.33, 95% CI [0.20, 0.46], P < .00001), and NK cells (WMD = 9.5, 95% CI [7.25, 11.76], P < .00001), decrease the incidence of leukopenia (RR = 0.52, 95% CI [0.44, 0.61], P < .00001), platelet toxicity (RR = 0.62, 95% CI [0.50, 0.76], P < .00001), and vomiting (RR = 0.72, 95% CI [0.60, 0.87], P = .0006). Based on the system evaluation results, the GRADE system recommendation grading method was adopted to evaluate the evidence quality. The results showed that the level of evidence was low. CONCLUSIONS The AGI apparently has attenuation and synergistic efficacy to platinum-based chemotherapy patients. However, considering the limits of articles included in the present researches, the recommendation is likely to be weak. High-quality RCTs are urgently used to generate conclusive results.
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Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active rheumatoid arthritis (TRIFRA): a randomised, controlled clinical trial.
Lv, QW, Zhang, W, Shi, Q, Zheng, WJ, Li, X, Chen, H, Wu, QJ, Jiang, WL, Li, HB, Gong, L, et al
Annals of the rheumatic diseases. 2015;(6):1078-86
Abstract
OBJECTIVES To compare the efficacy and safety of Tripterygium wilfordii Hook F (TwHF) with methotrexate (MTX) in the treatment of active rheumatoid arthritis (RA). METHODS Design: a multicentre, open-label, randomised controlled trial. All patients were assessed by trained investigators who were unaware of the therapeutic regimen. INTERVENTION 207 patients with active RA were randomly allocated (1:1:1) to treatment with MTX 12.5 mg once a week, or TwHF 20 mg three times a day, or the two in combination. At week 12, if reduction of the 28-joint count Disease Activity Score (DAS28) was <30% in the monotherapy groups, the patient was switched to MTX+TwHF. The primary efficacy point was the proportion of patients achieving an American College of Rheumatology (ACR) 50 response at week 24. RESULTS 174/207 (84.1%) patients completed 24 weeks of the trial. In an intention-to-treat analysis, the proportion of patients reaching the ACR50 response criteria was 46.4% (32/69), 55.1% (38/69) and 76.8% (53/69), respectively, in the MTX, TwHF and MTX+TwHF groups (TwHF vs MTX monotherapy, p=0.014; MTX+TwHF vs MTX monotherapy, p<0.001). Similar statistically significant patterns at week 24 were found for ACR20, ACR70, clinical Disease Activity Index good responses, EULAR good response, remission rate and low disease activity rate. Significant improvement in the Health Assessment Questionnaire and 36-item Short-Form Health Survey questionnaire scores from baseline to week 24 was seen in each treatment arm (p<0.05), though no significant difference was found among the treatment arms (p>0.05). The result of per-protocol analysis agreed with that seen in the intention-to-treat analysis. Seven, three and five women in the TwHF, MTX and combination groups, respectively, developed irregular menstruation (TwHF vs MTX monotherapy, p=0.216). CONCLUSIONS TwHF monotherapy was not inferior to, and MTX+TwHF was better than, MTX monotherapy in controlling disease activity in patients with active RA. TRIAL REGISTRATION NUMBER NCT01613079.
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Extraction optimization, characterization and immunity activity of polysaccharides from Fructus Jujubae.
Cui, G, Zhang, W, Wang, Q, Zhang, A, Mu, H, Bai, H, Duan, J
Carbohydrate polymers. 2014;:245-55
Abstract
The versatile Fructus Jujubae is widely used in Chinese and Korean traditional medicine. In this study, the extraction optimization, characterization and immunostimulatory activities of polysaccharides from Fructus Jujubae were investigated. Based on a four-variable-three-level Box-Behnken statistical design, the optimal extraction parameters were optimized as follows: extraction temperature 90 °C, extraction time 3.23 h, water to raw material ratio 33:1 and extraction 3 times. Under these conditions, the experimental yield of polysaccharides was 6.47 ± 0.26%, which was close to the predicted yield value (6.54%). The crude Fructus Jujubae polysaccharide was further purified by DEAE-cellulose chromatography repeatedly, and two homogenous fractions, designated as RQP1d and RQP2d with molecular weight of 83.8 and 123.0 kDa respectively, were obtained. Their structures were determined by chemical analysis, Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). Finally, preliminary immunological tests indicated that both RQP1d and RQP2d significantly stimulated NO production in RAW264.7 macrophages, and promoted LPS-induced splenocyte proliferation. These data implied Fructus Jujubae polysaccharides had the potential to be explored as novel natural immunostimulant for using in functional foods or medicine.