Genus Paeonia monoterpene glycosides: A systematic review on their pharmacological activities and molecular mechanisms.

BACKGROUND: Genus Paeonia, which is the main source of Traditional Chinese Medicine (TCM) Paeoniae Radix Rubra (Chishao in Chinese), Paeoniae Radix Alba (Baishao in Chinese) and Moutan Cortex (Mudanpi in Chinese), is rich in active pharmaceutical ingredient such as monoterpenoid glycosides (MPGs). MPGs from Paeonia have extensive pharmacological effects, but the pharmacological effects and molecular mechanisms of MPGs has not been comprehensively reviewed. PURPOSE: MPGs compounds are one of the main chemical components of the genus Paeonia, with a wide variety of compounds and strong pharmacological activities, and the structure of the mother nucleus-pinane skeleton is similar to that of a cage. The purpose of this review is to summarize the pharmacological activity and mechanism of action of MPGs from 2012 to 2023, providing reference direction for the development and utilization of Paeonia resources and preclinical research. METHODS: Keywords and phrases are widely used in database searches, such as PubMed, Web of Science, Google Scholar and X-Mol to search for citations related to the new compounds, extensive pharmacological research and molecular mechanisms of MPGs compounds of genus Paeonia. RESULTS: Modern research confirms that MPGs are the main compounds in Paeonia that exert pharmacological effects. MPGs with extensive pharmacological characteristics are mainly concentrated in two categories: paeoniflorin derivatives and albiflflorin derivatives among MPGs, which contains 32 compounds. Among them, 5 components including paeoniflorin, albiflorin, oxypaeoniflorin, 6'-O-galloylpaeoniflorin and paeoniflorigenone have been extensively studied, while the other 28 components have only been confirmed to have a certain degree of anti-inflammatory and anticomplementary effects. Studies of pharmacological effects are widely involved in nervous system, endocrine system, digestive system, immune system, etc., and some studies have identified clear mechanisms. MPGs exert pharmacological activity through multilateral mechanisms, including anti-inflammatory, antioxidant, inhibition of cell apoptosis, regulation of brain gut axis, regulation of gut microbiota and downregulation of mitochondrial apoptosis, etc. CONCLUSION: This systematic review delved into the pharmacological effects and related molecular mechanisms of MPGs. However, there are still some compounds in MPGs whose pharmacological effects and pharmacological mechanisms have not been clarified. In addition, extensive clinical randomized trials are needed to verify the efficacy and dosage of MPGs.

Long-circulating doxorubicin and Schizandrin A liposome with drug-resistant liver cancer activity: in vitro and in vivo evaluation.

Co-loading doxorubicin (DOX) and Schizandrin A (SchA) long-circulating liposome (SchA-DOX-Lip) have been confirmed to have good antitumor activity in vitro. However, in vivo pharmacodynamics, targeting, safety, and mechanism of action of SchA-DOX-Lip still need to be further verified. We investigated the tumor inhibition effect, targeting, safety evaluation, and regulation of tumor apoptosis-related proteins of the SchA-DOX-Lip. MTT assay was used to investigate the inhibitory effect of SchA-DOX-Lip on CBRH7919 cells. The drug uptake of CBRH7919 cells was observed by inverted fluorescence microscope. The tumor-bearing nude mice models of CBRH7919 were established, and the anti-tumor effect of SchA-DOX-Lip in vivo was evaluated by tumor biological observation, H&E staining, and TUNEL staining. The distribution and targeting of SchA-DOX-Lip in nude mice models were investigated by small animal imaging and tissue distribution experiment of CBRH7919. The biosafety of SchA-DOX-Lip was evaluated by blood routine parameters, biochemical indexes, and H&E staining. The expression of tumor-associated apoptotic proteins (Bcl-2, Bax, and Caspase-3) was detected by immunohistochemistry anvd western blotting. The results showed that SchA-DOX-Lip had cytotoxicity to CBRH7919 cells which effectively inhibited the proliferation of CBRH7919 cells, improved the uptake of drugs by CBRH7919 cells and the targeting effect of drugs on tumor site. H&E staining and biochemical detection results showed that SchA-DOX-Lip had high biosafety and did not cause serious damage to normal tissues. Western-blotting and TUNEL staining results showed that SchA-DOX-Lip could improve the regulatory effect of drugs on tumor apoptosis proteins. It was demonstrated that SchA-DOX-Lip had high safety and strong tumor inhibition effects, providing a new method for the clinical treatment of hepatocellular carcinoma (HCC).

Efficient synthesis and evaluation of novel 6-arylamino-[1,2,4]triazolo[4,3-a]pyridine derivatives as antiproliferative agents.

Based on our previous work, a series of novel 6-arylamino-[1,2,4]triazolo[4,3-a]pyridine derivatives were synthesized, and evaluated for antiproliferative activities. SAR studies revealed that inserting an amino linkage between 6­aryl group and [1,2,4]triazolo[4,3-a]pyridine core led to amuch broaderantitumorspectrum, and the most promising compound 8 l exerted potent andbroad-spectrum antiproliferative activity toward HeLa, HCT116, MCF-7, and A549 cell lines, with IC50 values in the micromolar range of 5.98-12.58 µM, which were more active than the positive control 5-FU. The mechanism investigation illustrated that 8 l dose-dependently caused cell cycle arrest at the G2/M phase, and induced cell apoptosis in HeLa cells. Consequently, these findings suggest the 6-arylamino-[1,2,4]triazolo[4,3-a]pyridines afford significant potential for the discovery of a new highly efficient anticancer agents.

Long-circulating doxorubicin and schizandrin A liposome with drug-resistant liver cancer activity: preparation, characterization, and pharmacokinetic.

The selectivity of chemotherapeutic agents for liver cancer is poor. When they kill tumour cells, they produce serious adverse reactions in the whole body and multidrug resistance (MDR) is also a major hurdle in liver cancer chemotherapy. Combination therapy is a useful method for overcoming MDR and reducing toxic and side effects. In this study, we developed a long-circulating codelivery system, in which doxorubicin (DOX) and schizandrin A (SchA) are combined against MCF-7/ADR cells. The DOX-SchA long-circulating liposome (DOX-SchA-Lip) was prepared using ammonium sulphate gradient method. The two drugs were co-encapsulated into the distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-mPEG2000) liposome and the liposome had an average particle size of (100 ± 3.5) nm and zeta electrical potential of (-31.3 ± 0.5) mV. The average encapsulation rate of DOX was 97.98% and that of SchA was 86.94%. DOX in liposome had good sustained-release effect. The results showed that DOX-SchA-Lip could significantly prolong the half-life (t1/2z) of the DOX and SchA, increase their circulation time in vivo, improve its bioavailability and reduce their side effects. Liposome can effectively induce early apoptosis of HepG2/ADR cells and the cell cycle was blocked in S-phase by DOX-SchA-Lip in a dose-dependent manner. The IC50 of compound liposome to HepG2 and HepG2/ADR were 0.55 µmol/L and 1.38 µmol/L, respectively, which could significantly reverse the resistance of HepG2/ADR and the reversion multiple was 30.28. It was verified that DOX-SchA-Lip can effectively kill tumour cells and reverse MDR.

An in vitro and in vivo study of the role of long non-coding RNA-HOST2 in the proliferation, migration, and invasion of human glioma cells.

Gliomas are the most commonly occurring primary malignant brain tumors in the central nervous system of adults. They are rarely curable and the prognosis for high grade gliomas is generally poor. Recently, long non-coding RNA (lncRNA) human ovarian cancer-specific transcript 2 (HOST2) has been reported to be expressed at high levels in human ovarian cancer, involving tumorigenesis. However, little is still known about whether and how HOST2 regulates glioma development and progression. Therefore, this study aims to investigate the role of HOST2 in human glioma cells. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to determine the expression of lncRNA HOST2, let-7b, and PBX3 in human glioma cells. Cultured human glioma cells were treated with siRNA (si)-lncRNA HOST2, let-7b mimic, si-lncRNA HOST2 + let-7b inhibitor, and si-PBX3. Parameters including cell viability, colony formation, cell migration, and cell invasion were detected by cell counting kit-8 assay, colony formation assay, scratch test, and Transwell assay respectively to determine the effects of down-regulated HOST2 on glioma cells. Tumor formation in nude mice was evaluated by subcutaneous tumor formation experiment. Results showed that HOST2 and PBX3 were highly expressed in glioma tissue whereas let-7b was expressed at much lower levels. In response to treatment with si-lncRNA HOST2, si-PBX3, and let-7b mimic, glioma cell lines exhibited decreased cell viability, suppressed cell migration, invasion, and reduced colony formation of glioma cells. This was accompanied by an attenuated tumor formation with smaller volume and weight in nude mice, suggesting that down-regulated HOST2 could inhibit the tumorigenicity of glioma cells. Lastly, we found that lncRNA HOST2 was highly expressed in glioma tissues and its down-regulation could inhibit the growth and invasion of glioma cells. © 2018 IUBMB Life, 71(1):93-104, 2019.

[Digital Identification Based on Image Processing for Mountain Cultivated Ginseng].

Objective: To identify mountain cultivated ginseng using a digital method. Methods: Image information of mountain cultivated ginseng was processed using the Matlab 2014 a software box. Based on the shape, color and texture features,18 image information from ginseng rhizome, body, grain, peel, fibrous root, were extracted and a digital mountain cultivated ginseng database model was established. Results: Digital identification based on image processing could be met by the features obtained from mountain cultivated ginseng. The recognition rate of ginseng was 96%. Conclusion: A lot of information from ginseng were extracted based on image processing. A fast and accurate digital identification of mountain cultivated ginseng is achieved successfully undamaged.

[Fingerprint comparison of mountain cultivated ginseng and wild ginseng by HPLC].

OBJECTIVE: To establish the fingerprint of mountain cultivated ginseng by HPLC and compare the fingerprint with that of wild ginseng for the quality control. METHODS: The analysis was carried out on a ZORBAX Eclipse XDB-C18 column (150 mm x 4.6 mm, 5 microm) with a mobile phase consisting of water-acetonitrile with gradient elution, and the flow rate was 1 mL/min. The column temperature was set at (30 +/- 0.15) degrees C and UV detection wavelength was set at 203 nm. RESULTS: There were 15 common peaks in the fingerprint of mountain cultivated ginseng. The similarities of 10 batches ginseng were between 0.90 and 1.00. CONCLUSION: This method has good characteristics and specificity, and could be used for quality control of mountain cultivated ginseng. The type and content of components in wild ginseng were slightly higher than those in mountain cultivation ones.

The life of a Canadian doula: successes, confusion, and conflict.

OBJECTIVE: Despite evidence that doulas improve maternal and newborn outcomes, some maternity care professionals have had difficulty both in understanding the role of doulas and in accepting doulas as collaborators. We sought to examine the backgrounds, practices, and professional motivations of doulas and to understand their role and interactions with other maternity care providers. METHODS: We conducted a postal survey of 212 Canadian doulas whose contact information was provided by DONA International. The main outcome measures of the survey were demographics, practices, motivations, perception of working environment, interactions with and acceptance by other maternity care providers, and overall work satisfaction. RESULTS: The most common reasons for becoming a doula were the desire to support women in childbirth, personal interest, and a wish to share their own positive birth experience with others. Only 21.7% described the doula role as a means of achieving personal financial support. Most respondents intended to continue doula work in the next five years. Doulas felt more accepted by midwives than other care providers. Most doulas reported no conflict with other maternity care providers, but on rare occasions, doulas had been excluded from attending birth by maternity care providers, hospital and/or administrative regulations, and rarely by a client. Almost all doulas (98.5%) rated their overall professional experience as good or excellent. CONCLUSION: Better recognition and respect from other providers significantly influenced doulas' satisfaction. This study helps clarify areas of possible conflict and obstacles that doulas may face in their work environment and in their interactions with other maternity care providers.