Targeted Drug Delivery Systems for Curcumin in Breast Cancer Therapy.

Breast cancer (BC) is the most prevalent type of cancer in the world and the main reason women die from cancer. Due to the significant side effects of conventional treatments such as chemotherapy and radiotherapy, the search for supplemental and alternative natural drugs with lower toxicity and side effects is of interest to researchers. Curcumin (CUR) is a natural polyphenol extracted from turmeric. Numerous studies have demonstrated that CUR is an effective anticancer drug that works by modifying different intracellular signaling pathways. CUR's therapeutic utility is severely constrained by its short half-life in vivo, low water solubility, poor stability, quick metabolism, low oral bioavailability, and potential for gastrointestinal discomfort with high oral doses. One of the most practical solutions to the aforementioned issues is the development of targeted drug delivery systems (TDDSs) based on nanomaterials. To improve drug targeting and efficacy and to serve as a reference for the development and use of CUR TDDSs in the clinical setting, this review describes the physicochemical properties and bioavailability of CUR and its mechanism of action on BC, with emphasis on recent studies on TDDSs for BC in combination with CUR, including passive TDDSs, active TDDSs and physicochemical TDDSs.

Review targeted drug delivery systems for norcantharidin in cancer therapy.

Norcantharidin (NCTD) is a demethylated derivative of cantharidin (CTD), the main anticancer active ingredient isolated from traditional Chinese medicine Mylabris. NCTD has been approved by the State Food and Drug Administration for the treatment of various solid tumors, especially liver cancer. Although NCTD greatly reduces the toxicity of CTD, there is still a certain degree of urinary toxicity and organ toxicity, and the poor solubility, short half-life, fast metabolism, as well as high venous irritation and weak tumor targeting ability limit its widespread application in the clinic. To reduce its toxicity and improve its efficacy, design of targeted drug delivery systems based on biomaterials and nanomaterials is one of the most feasible strategies. Therefore, this review focused on the studies of targeted drug delivery systems combined with NCTD in recent years, including passive and active targeted drug delivery systems, and physicochemical targeted drug delivery systems for improving drug bioavailability and enhancing its efficacy, as well as increasing drug targeting ability and reducing its adverse effects.

Integrated dose-response metabolomics with therapeutic effects and adverse reactions may demystify the dosage of traditional Chinese medicine.

BACKGROUND: Traditional Chinese medicine (TCM) has been used to treat various diseases for thousands of years. However, the uncertainty of dosage as well as the lack of systemic evaluation of pharmacology and toxicology is one major reason why TCM remains mysterious and is not accepted worldwide. Hence, we aimed to propose an integrated dose-response metabolomics strategy based on both therapeutic effects and adverse reactions to guide the TCM dosage in treatment. METHODS: The proposed methodology of integrated dose-response metabolomics includes four steps: dose design, multiple comparison of metabolic features, response calculation and dose-response curve fitting. By comparing the changes of all metabolites under different doses and calculating these changes through superposition, it is possible to characterize the global disturbance and thus describe the overall effect and toxicity of TCM induced by different doses. Rhubarb, commonly used for constipation treatment, was selected as a representative TCM. RESULTS: This developed strategy was successfully applied to rhubarb. The dose-response curves clearly showed the efficacy and adverse reactions of rhubarb at different doses. The rhubarb dose of 0.69 g/kg (corresponding to 7.66 g in clinic) was selected as the optimal dose because it was 90% of the effective dose and three adverse reactions were acceptable in this case. CONCLUSION: An integrated dose-response metabolomics strategy reflecting both therapeutic effects and adverse reactions was established for the first time, which we believe is helpful to uncover the mysterious veil of TCM dosage. In addition, this strategy benefits the modernization and internationalization of TCM, and broadens the application of metabolomics.

Evaluation of the Clinical Efficacy of the Classic Prescription "Baihe Dihuang Decoction" Based on Meta-Analysis.

Purpose: To explore the clinical application of Baihe Dihuang Decoction. To provide certain data support and theoretical basis for the clinical application of Baihe Dihuang Decoction in the future. Methods: With "Baihe Rehmannia Tang" as the search term, the search was carried out on CNKI, VIP, Wanfang, PubMed and other databases. The statistical analysis of Baihe Dihuang decoction for treating diseases was obtained. Meta-analysis of the data was performed using RevMan 5.3 software to analyze the main therapeutic indicators of the disease. Results: According to the 83 valid literature that can be found, it is shown that 17 are used for the treatment of depression, 14 are used for the treatment of menopausal syndrome, 24 are used for the treatment of insomnia, and 28 are used for the treatment of other diseases. Conclusion: In the treatment of depression, menopausal syndrome, and insomnia combined with Baihe Dihuang Decoction can have a better therapeutic effect and diminish the incidence of adverse reactions. It provides a theoretical basis for the study and experimental study of its active components.

[Application of particle design technology in field of traditional Chinese medicine powder].

Solid preparations account for more than 50% of traditional Chinese medicines(TCM). TCM powder is an important raw material for solid preparations of TCM. Its powder properties directly affect the quality of solid preparations, and even clinical safety and effectiveness. Particle design technology based on the characteristics of powder in TCM is an important means to improve and enhance the quality of solid preparations. This study summarized the relevant principles, methods, characteristics, classification, equipment, and other elements of particle design technology in recent years, analyzed the difficulties in its application in the field of TCM powder, and proposed the strategies in conjunction with the development of computer data mining. The present study is expected to provide a reference for the suitability of particle design in the field of TCM powder.

[Application of design technology for preparing Lingzhu Powder particles based on solvent evaporation method].

Targeting the deficiencies of Lingzhu Powder, this study introduced the particle design technology to improve its quality. Based on the mechanism of particle design for powder and the characteristics of solvent evaporation method, composite particles consisting of Succinum, Cinnabaris, and artificial Bovis Calculus were prepared. And the powder properties of composite particles and physical mixtures as well as the content uniformity of toxic components were investigated for exploring the technological advantages of particle design in improving the quality of Lingzhu Powder. The results showed that the composite particles prepared using solvent evaporation method and particle design technology were micro-particles, and the stable agglomerate structure could be observed under SEM. Composite particles exhibited better fluidity and compliance in oral intake than physical mixtures. The differences in chromatism, bulk density, and content uniformity of the composite particles were smaller than those of physical mixtures, and the corresponding RSD values \[4.8%, 1.8%, 3.4%(bilirubin), and 0.63%(HgS), respectively\] were smaller. The solvent evaporation combined with particle design technology can be utilized to significantly improve the quality of Lingzhu Powder, which has provided new ideas for the optimization of the quality of traditional Chinese medicinal powder.

[Particle design for improving taste and homogeneity of traditional Chinese medicinal powder: taking Zhuhuang Chuihou Powder as an example].

Due to the complex source and different physical and chemical properties of traditional Chinese medicines(TCM) powder, there are many common pharmaceutical problems in its preparation, such as large particle size difference, poor mixing uniformity, and poor compliance with oral intake, which has directly affected the quality of solid preparations as well as their clinical efficacy and safety. This study observed the property of Zhuhuang Chuihou Powder and extract its pharmaceutical defects. It was found that realgar and calcined Borax in Zhuhuang Chuihou Powder were heavy in texture and toxic, and they were easy to be isolated, indicating the potential safety hazard. At the same time, Coptidis Rhizoma and Phellodendri Chinensis Cortex were the main sources of its bitterness. Therefore, based on the idea of "drug-excipients unity", the particle design technology was used to prepare core/shell-type composite particles with bitter medicines as the core and mineral medicines as shell. Both infrared spectroscopy and scanning electron microscopy results indicated the formation of composite particles, and the taste of these composite particles were improved. Compared with the physical mixtures, the composite particles exhibited significantly decreased RSD values in the content uniformity of berberine hydrochloride, arsenic disulfide, and sodium tetraborate and appearance uniformity. The introduction of particle design technology solved the problem of uneven dispersion of Zhuhuang Chuihou Powder, thus ensuring its uniform dispersion, stability, and control and improving the quality of the original preparation. This has provided a scientific basis for the quality control of TCM powder.

[Particle design for improving content uniformity of Hewei Jiangni Capsules].

Targeting the poor powder characteristics of the contents in Hewei Jiangni Capsules, this study characterized the powder properties of the contents and employed particle design technique for improving the content quality. The content composite particles of Hewei Jiangni Capsules prepared by the particle design technique were evaluated by scanning electron microscopy(SEM), followed by infrared ray(IR), content uniformity, and in vitro dissolution detection. It was found that there was a good correlation between the crushed particle size of slices and the crushing time, and the calcined Haematitum was responsible for the poor content uniformity. After the fine powder of calcined Haematitum was super-finely ground for 8.5 min and those of the other contents in the capsule for 1 min, they were prepared into the composite particles, whose property characterizations were compared with those of the physical mixtures. The content uniformity of the prepared composite particles was significantly improved, and the preparation process was stable and reliable. The adoption of particle design technology to correct the poor uniformity of the physical mixture, solve the pharmaceutical defects of Hewei Jiangni Capsules, and improve the quality of prescriptions has provided important reference for the clinical application and development of Chinese medicinal preparations.

[Powder modificationfor improving content uniformity of Ziyin Yiwei Capsules].

Based on the defects in powder properties of the contents of Ziyin Yiwei Capsules, this study screened out the main medicinal slice powders causing the poor powdery properties, and introduced the powder modification process to improve the powdery properties of these slice powders, the pharmaceutical properties of the capsule contents, and the content uniformity of Ziyin Yiwei Capsules, so as to provide a demonstration for the application of powder modification technology to the preparation of Chinese medicinal solid preparations. Through the investigation on the powder properties of the contents of Ziyin Yiwei Capsules, it was clarified that the pulverized particle size of the capsule contents had a good correlation with the pulverization time. According to the measurement results of the powder fluidity and wettability, the quality defects of the capsule contents were caused by the fine powders of Taraxaci Herba and Lungwortlike Herba. "Core-shell" composite particles were prepared from medicinal excipients magnesium stearate and fine powders of Taraxaci Herba and Lungwortlike Herba slices after ultra-fine pulverization to improve the powder properties of the problematic fine powders. Powder characterization data including fluidity and wettability were measured, followed by scanning electron microscopy(SEM) and infrared ray(IR) detection. It was determined that the optimal dosage of magnesium stearate was 2%, and the compositing time was 3 min. The composite particles were then used as content components of the Ziyin Yiwei Capsules. The powder characteristics between the original capsule and the modified composite capsule including the particle size, fluidity, wettability, uniformity of bulk density, and uniformity of chromatism as well as the content uniformity and in vitro dissolution were compared. The results showed that the powder characteristics and content uniformity of the prepared composite capsule were significantly improved, while the material basis of the preparation was not changed before and after modification. The preparation process was proved to be stable and feasible. The powder modification technology solved the pharmaceutical defects that were easy to appear in the preparation of traditional capsules, which has provided experimental evidence for the use of powder modification technology for improving the quality of Chinese medicinal solid preparations and promoting the secondary development and upgrading of traditional Chinese medicinal dosage forms such as capsules.

[Quality evaluation of Aralia taibaiensis based on spectrum-activity relationship].

A spectrum-activity relationship is established with high performance liquid chromatography(HPLC) fingerprints and the in vitro antioxidant activity to improve the quality evaluation system of Aralia taibaiensis. The HPLC profiles of 12 batches of samples were collected, and the similarity evaluation, heat map analysis and principal component analysis were conducted for the chemometric study of the fingerprint data. Combined with grey correlation analysis, the contributions of the common peaks in the fingerprints to the antioxidant activity were clarified, and the important peaks reflecting the efficacy were identified. The results showed that 17 common peaks were found in 12 batches of A. taibaiensis samples, and 6 of them were identified as saponins. Similarity evaluation, heat map analysis and principal component analysis roughly classified the A. taibaiensis herbs into two categories, i.e.,(1) S1-S10, S12 and(2) S11. Twelve batches of samples showed different antioxidant activities in a dose-dependent manner. In particular, S9 had the strongest antioxidant activity, while S11 was the weakest in antioxidant capacity, which was basically consistent with the overall score results. The results of grey correlation analysis demonstrated that the 17 common peaks scavenged DPPH radicals in the following order: X_3>X_(17)>X_4>X_8>X_7>X_(13)>X_2>X_6>X_(11)>X_(10)>X_(16)>X_(12)>X_9>X_5>X_(14)>X_1>X_(15), and scavenged ABTS radicals in the order of X_4>X_3>X_7>X_8>X_2>X_(17)>X_(13)>X_6>X_(16)>X_(11)>X_5>X_(12)>X_(10)>X_9>X_(14)>X_1>X_(15). Among them, X_3, X_4, X_7(araloside C), X_8 and X_(17) were the important peaks reflecting the efficacy of A. taibaiensis, which were basically consistent with those contained in the principal component 1. In this study, the correlation between the HPLC fingerprints of 12 batches of A. taibaiensis and its antioxidant activity provides a reference for the Q-marker screening and quality control of A. taibaiensis.

Exploring the Mechanism of Lingzhu San in Treating Febrile Seizures by Using Network Pharmacology.

OBJECTIVE: Lingzhu San (LZS) is a traditional Chinese medicine (TCM) prescription that can be effective in treating febrile seizures (FS) and there are few research works conducted on its mechanisms. In order to better guide the clinical use of LZS, we used the research ideas and methods of network pharmacology to find the potential core compounds, targets and pathways of LZS in the complex TCM system for the treatment of FS, and predict the mechanism. MATERIALS AND METHODS: Databases such as BATMAN, TCMSP, TCMID, and SWISS TARGET are used to mine the active compounds and targets of LZS, and the target information of FS is obtained through GENECARDS and OMIM. Using Venny2.1.0 and Cytoscape software, the potential core compounds and targets of FS were obtained. The R language and ClusterProfiler software package are adopted to enrich and analyze the KEGG and GO pathways of the core targets and the biological processes and potential mechanisms of the core targets are also revealed. RESULTS: 187 active compounds and 2113 target proteins of LZS were collected. And 38 potential core compounds, 35 core targets and 775 metabolic and functional pathways were screened, which were involved in mediating FS. Finally, the role of the core compounds, targets and pivotal pathways of LZS in regulating FS in the pathogenesis and the therapeutic mechanism of FS were discussed and clarified. CONCLUSION: In this paper, the multi-compounds, multi-targets and multi-pathways mechanism of LZS in the treatment of FS were preliminarily screened through the analysis of network pharmacology data, which are consistent with the principle of multi-compounds' compatibility with TCM prescriptions and a unified treatment of diseases from multiple aspects, and it provides a new way for TCM to treat complex diseases caused by multiple factors.

Analysis of Clinical Efficacy of Traditional Chinese Medicine in Recovery Stage of Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: We provide an updated meta-analysis with detailed information on a combination of TCM and routine treatment. METHODS: Retrieve appropriate articles with no language restrictions on keywords until 8 July 2019 in an electronic database. All trajectories are screened according to certain criteria. The quality of certified research was also evaluated. We made a detailed record of the results of the measurement. Meta-analysis was carried out by using the Revman 5.3 software. RESULTS: Sixty-seven RCTs were included, and 6594 subjects were analyzed. Compared with routine treatment, the total effective rate (TER) of TCM combined with routine treatment was improved, and the recovery of stroke was also significantly accelerated. Regulation of blood lipids by notably shrinking the contents of TC, TG, and LDL and enhancing the levels of HDL. The levels of serum hs-CRP, WHV, and WLV decreased significantly, indicating that the expression of thrombomodulin was decreased after the comprehensive treatment of traditional Chinese medicines (TCMs). The combination of TCM treatment could enhance the protection of neural function by decreasing the NIHSS scoring while increasing the BI scoring. Paeoniae Radix Rubra, Angeticae Sinensis Radix, etc., can effectively improve the clinical symptoms of stroke convalescent patients and promote the recovery of neurological function. ACU of Baihui, Renzhong, etc., can improve the clinical rehabilitation effect of patients. However, our findings must be handled with care because of the small sample size and low quality of clinic trials cited. Other rigorous and large-scale RCTs are in need to confirm these results. CONCLUSION: A combination of TCM and routine treatment in the treatment of stroke could improve TER, and it is beneficial to the rehabilitation of patients in the recovery period of apoplexy. These effects can be mediated by a combination of several mechanisms. Nevertheless, due to the limitations of this study, these results should be handled with caution.

Evaluation of the Therapeutic Effect of Traditional Chinese Medicine on Osteoarthritis: A Systematic Review and Meta-Analysis.

Background: Osteoarthritis (OA) is a common degenerative disease of bone and joint characterized by the damage of articular cartilage and hypertonia, which often occurs in the middle-aged and elderly. Traditional Chinese medicine (TCM) therapy, including acupuncture (ACU), oral administration, and external use of traditional Chinese medicines (TCMs), can significantly improve the therapeutic effect on OA and reduce the occurrence of side effects. We provide a latest meta-analysis on the treatment of OA with TCM. Materials and Methods: In the electronic database, appropriate articles without language restrictions on keywords were selected until August 1, 2019. All trajectories are screened according to certain criteria. The quality of qualified research was also assessed. We have made a detailed record of the results of the measurement. Meta-analysis was carried out with Revman 5.3 software. Results: Forty-four articles involving 4014 patients (2012 cases in the experimental group and 2002 cases in the control group) with OA were selected. This article focuses on the study of the treatment of OA by using the general mode of TCM. The quality evaluation included in the study was evaluated independently according to the Cochrane intervention system evaluation manual. In this meta-analysis, 68.18% of the literature correctly described the conditions for the generation of random assignment sequences, only 6.82% of the literature correctly mentioned the hidden details of allocation, and all studies mentioned randomly assigned participants. Compared with Western medicine, the total effective rate (TER) of OA treatment in TCM was significantly increased and the recurrence rate (RR) was significantly decreased (P < 0.00001). In addition, the experimental group was also superior to the control group in terms of the indicators of joint activity function, inflammatory factor content, and various indicators affecting bone metabolism. It can be showed by the network analysis diagram that Aconiti Radix, Achyranthis Bidentatae Radix, and other TCMs can inhibit inflammatory stimulation and relieve the pain symptoms of patients with OA. ACU at Yinlingquan, Xiyan, and other acupoints can effectively improve the clinical symptoms of patients with OA. Conclusion: TCM therapy in treatment of patients with OA could effectively restore joint function, enhance the TER, and reduce RR. However, the results of this study should be handled with care due to the limitations existing. Some rigorous randomized controlled trials (RCTs) are needed to confirm these findings.

[Experimental study on protective effect and mechanism of Shengdihuang Decoction on ovary of rats with premature ovarian failure].

The aim of this paper was to investigate the protective effect of Shengdihuang Decoction(SDHD) on premature ovarian failure in rats and to explore its protective mechanism. Totally 48 adult female SD rats were randomly divided into six groups with 8 rats in each group: control group,model group,Bujiale group,SDHD high,medium and low dose group(12,6,3 g·kg-1). Rats were administered with Tripterygium Glycosides Tablets for 14 d to make model of premature ovarian failure except for control group. Rats were treated with corresponding medicines for 21 d after that. The oestrous cycle was observed,ovarian index and uterine index were detected,respectively. The variation in contents of E2,P,FSH,LH was detected with radioimmunoassay,the morphological changes of ovary and uterus were observed by HE staining,SOD activity and MDA content were detected in serum. The expression of ERα in ovarian and uterine tissues was detected by SABC,and the expression of ERα in uterus tissue was detected by Western blot. Compared with the model group,the index of the uterus and ovary in the high and middle dose group of Shengdihuang Decoction increased(P<0. 05),the level of serum E2 and P increased(P<0. 01,P<0. 05) and the level of LH decreased(P<0. 01). The number of ovarian follicles increased,the endometrium thickened,and the glands were developed,the activity of SOD was enhanced and the content of MDA decreased in serum,the expression of ERα in the follicle granulosa cells and the epithelial cells of the uterus increased,and the expression of ERα in the uterus increased. Shengdihuang Decoction could improve the morphology and function of the uterus and ovary,and relieve the premature failure of the ovary. The effect may be achieved by enhancing the antioxidant capacity of ovarian granulosa cells,restoring ovarian function,promoting serum estradiol and progesterone secretion,and increasing the expression of ER in uterine mucosal epithelial cells and ovarian granulosa cells.

Therapeutic Efficacy of Kangfuxin Liquid Combined with PPIs in Gastric Ulcer.

OBJECTIVE: To evaluate the clinical efficacy and safety of Kangfuxin liquid (KFX) combined with proton pump inhibitors (PPIs) in the treatment of gastric ulcer (GU). MATERIALS AND METHODS: Electronic databases including PubMed, Wanfang, CNKI, VIP, Embase, Cochrane Library, and CBM were examined for appropriate articles without language limitations on key words before March 10, 2019. RevMan 5.3 software was applied to execute outcome assessment and finish the meta-analysis. RESULTS: 22 articles involving 2,024 patients with a gastric ulcer were selected. Total efficacy rate and efficacy rate of gastroscopy were significantly enhanced for the combination of KFX with PPIs compared to those of PPI treatment alone (OR = 6.95, 95% CI: 4.87, 9.91, P < 0.00001; OR = 2.96, 95% CI: 1.98, 4.42, P < 0.00001, respectively). Same results were found for different PPIs in combination on total efficacy rate, respectively. The combination also significantly reduced the adverse events (OR = 0.39, 95% CI: 0.22, 0.70, P=0.002). In addition, KFX combined with PPI could suppress the inflammation (MD = -6.11, 95% CI: -7.45, -4.77, P < 0.00001), reduce the recurrence rate (OR = 0.31, 95% CI: 0.14, 0.70, P=0.005), and enhance the clearance rate of Helicobacter pylori (HP, OR = 3.76, 95% CI: 1.80, 7.87, P=0.0004). It seemed like the combination would influence immune function by increasing levels of T-lymphocyte subsets CD4 and CD8 but not CD3 (MD = 2.40, 95% CI: 1.25, 3.55, P < 0.0001); MD = 25.72, 95% CI: 14.55, 36.90, P < 0.00001; MD = 0.72, 95% CI: -0.66, 2.09, P=0.31, respectively). CONCLUSION: KFX combined with PPIs in treatment of patients with GU could improve the total efficacy rate and efficacy rate of gastroscopy and reduce adverse events and the recurrence rate. However, the results of this study should be handled with care due to the limitations. Several rigorous RCTs are in need to confirm these findings.

[Extraction kinetics of volatile oil from galangal by steam distillation].

To reveal the extraction regularity of volatile oil from galangal by GC-MS analysis. The volatile oil in galangal was extracted by steam distillation. The extract was collected every 30 min, the oil part and the water part were separated. GC-MS was used to analyze the extraction liquid collected at different time periods. A total of 140 volatile components were obtained by GC-MS analysis. Among them, the main components were eucalyptus oil alcohol, alpha-pine oil alcohol and 4-terpene alcohol; 22 special components were dissolved in water, 77 special components were dissolved in oil and 41 components were dissolved in both oil and water. With the increase of specific components in water, the content of Eucalyptus in water increased in a linear manner. The increase of eucalyptus oil further promoted the dissolution or dispersion of alpha PN in water, and the change of specific components in oil was positively correlated with the content of Eucalyptus and alpha-terpilenol in oil. The results of principal component analysis show that the physical and chemical properties of the compounds were important factors affecting the distribution of components. PC1 (molecular weight, melting point, boiling point positive correlation), PC2 (negative correlation of refractive index) and PC3 (positive correlation of water solubility) were the main components that lead to the differences in composition distribution. The process of extracting volatile oil from galangal through steam distillation was affected by the physical and chemical properties of volatile components. Some components were specifically distributed in the fragrance and volatile oil system. The endemic components of aromatic water increased the content of the main components in the water system, which may lead to the "emulsification", reduction of the yield and low quality of the volatile oil.