Plant-derived triterpenoids constitute a large and structurally diverse class of natural products with various implications in industrial and pharmaceutical uses. The oleanane type triterpenoids are widely known for their pharmacological and/or biological activities. The biosynthesis pathway of oleanane triterpenoids is divided into three stages:precursor supply, skeleton synthesis, and terpenoids synthesis. Plant cytochrome P450 monooxygenases enzymes (P450s) are involved in the synthesis and diversification of natural products, and are responsible for other modifications of terpenoids, such as formation of triterpenoids. P450s-catalyzed structural modification prior to glycosylation is crucial for diversification and functionalization of triterpenoid scaffolds. In this paper, the catalyses of P450s on β-amyrin and oleanolic acid in oleanane type triterpenoid saponins biosynthesis were reviewed. Presenegenin is a major aglycon of Polygala saponins. The CYP716A249 in Polygala tenuifolia was used as an example to other P450s participating in the possible biosynthetic pathways of presenegenin. These results provide references for elucidation of the biosynthesis pathways of plant-derived oleanane type triterpenoids.

Myeloproliferative neoplasms (MPNs) result from clonal expansion of haematopoietic stem cells and are characterized by abnormal proliferation of myeloid lineage cells in the bone marrow. Sustained activation of JAK-STAT signaling pathway due to JAK2 phosphorylation is an important cause of MPNs, and mutation of JAK2 kinase can keep it in a state of continuous phosphorylation. The most typical mutation in JAK2 is a site mutation of V617F in the pseudokinase domain. The JAK2V617F-activating mutation is highly prevalent in MPNs, with frequencies estimated at approximately 95% in polycythaemia vera (PV) and 50% in primary myelofibrosis (PMF) and essential thrombocytosis (ET) patients. It is now clear that JAK2 is an important target for treatment of MPNs. Inhibiting aberrant activation of the JAK2-STAT signaling pathway has become a popular trend in research for effective treatment of MPNs. This review summarizes the research progress in developing JAK2 inhibitors for treatment of MPNs in recent years, including the new discoveries of the biological functions of JAK2, the relationship between JAK2 and MPN, and the status of development of JAK2 small molecule inhibitors.

Alzheimer's disease (AD) is characterized clinically as irreversible cognitive dysfunction. Although a significant progress has been made in the study of AD pathogenesis, the effective measures to block AD progress have not been satisfactory. Abnormal autophagy is thought to be involved in the pathogenesis of AD, and regulation of autophagy may become a new strategy for AD treatment. Some medicines, which regulate autophagy by mTOR-dependent and independent (Bcl-2/Beclin-1, GSK-3β, and p-AKT) pathways, have shown excellent effects in alleviating AD symptoms. In addition, certain compounds extracted from plants have also been reported to regulate autophagy and prevent AD progression through multiple pathways and multiple targets. This article reviews the recent advances in the regulation of autophagy and AD treatment. It provides a new theoretical basis for clinical treatment of AD.

CAT3 is a promising anti-brain tumor agent that has significant anti-tumor activity on Daoy or U87MG orthotopic xenograft in nude mice. This study was carried out to investigate the metabolic profiles of CAT3 in mouse/dog/human blood and microsome as well as in humanized recombinant enzymes. All animal care and experimental procedures were reviewed and approved by the Animal Ethics Committee of Chinese Academy of Medical Sciences. Our findings showed that CAT3 could be hydrolyzed to active metabolite PF403 by carboxylesterase, butyrylcholinesterase and serine hydrolase in mouse/dog/human blood. PF403 could be further metabolized to M1 oxidative dehydration product, M2 double oxidation dehydration product, M3 methylation oxidative dehydration product, M4 oxidation product and M5 demethylation product, which were mainly catalyzed by CYP1A2, 1A1, 2C9 and 3A4, and slightly by CYP2B6, 2C8, 2C19 and 2D6. Besides oxidative metabolism, PF403 also was transformed into glucuronylation metabolites GLU-PF403 by Phase Ⅱ enzymes UGT1A1, 1A3 and 1A9. Taken together, the metabolism of CAT3 was a multiple enzyme catalytic reaction. These results could provide valuable information for potential enzyme-mediated DDI in clinic studies.

Urate transporter 1 (URAT1) is a validated target for the treatment of hyperuricemia. Based on the structure of URC-102, which is currently under a phase Ⅱ clinical trial, fourteen novel analogs were designed and synthesized. Among them, four compounds (9b, 9c, 10e and 10g) exhibited substantial inhibitory effect against URAT1. The most active compound 9b showed an IC₅₀ value of 0.061 μmol·L^-1, which is significantly more potent than Lesinurad and Benzbromarone. Preliminary SAR was drawn, providing clues for further structural optimization.

The drug delivery system with "gatekeeper" is designed to achieve a stable entrapment state of the payload under normal physiological conditions through the gatekeepers. With tumor microenvironment or stimulation of exogenous factors, the gatekeeper is detached or altered to promote the responsive release of the drug. In this paper, we focus on applications of stimuli-responsive linkages and stimuli-responsive groups, and review research progresses of drug delivery system with "gatekeeper" developed over the past 10 years.

Five alkaloids were isolated from a decoction of Uncaria rhynchophylla by a combination of various chromatographic techniques, including macroporous adsorbent resin, MCI resin, silica gel, Sephadex LH-20, and reversed phase HPLC. Their structures were characterized by comprehensive analyses of spectroscopic data as monoterpene indole alkaloids (+)-(7R)-3-oxo-7-hydroxy-3, 7-seco-dihydrorhynchohylline (1), (+)-(7S)-3-oxo-7-hydroxy-3, 7-seco-dihydrorhyncho-hylline (2), (+)-(7R)-3-oxo-7-hydroxy-3, 7-seco-rhynchohylline (3) and (+)-(7S)-3-oxo-7-hydroxy-3, 7-seco-rhynchohylline (4), and a β-carboline alkaloid 1, 2, 3, 4-tetrahydro-1-oxo-β-carboline (5). Among them, 1 and 2 are new compounds, 3 and 4 are new natural products that were semi-synthesized from isorhynchohylline with incorrect specific rotations, and 5 is isolated for the first time from the genus Uncaria.

The grading and quality analysis methods for different commercial Glycyrrhiza Polygalae Radix slices were established. The qualities of different grade samples were analyzed and compared, in order to provide useful information for the formulation of the grading standards of Glycyrrhiza Polygalae Radix slices. A total of 34 batches of Glycyrrhiza Polygalae Radix slice samples collected from 12 companies were divided into two grades:first-grade (diameter ≥ 3.0 mm) and second-grade (diameter < 3.0 mm). Thin-layer chromatography (TLC), multi-component content determination and fingerprint analysis were used to analyze the qualities of different grades of Glycyrrhiza Polygalae Radix slices, and the fingerprints were statistically analyzed using partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The results showed that the established TLC method can simultaneously identify three major types of components, including sugar esters, xanthones, and saponins in Glycyrrhiza Polygalae Radix slices, and has obvious advantage compared to the existing methods for its rich information, low cost, and easy or safe operation. The multi-component determination showed that the contents of three index components (polygalaxanthone Ⅲ, 3, 6'-disinapoyl sucrose and tenuifolin) in the first-grade products of Glycyrrhiza Polygalae Radix slices were lower than those in the second-grade products. The results of PLS-DA and OPLS-DA indicated significant differences were observed between the first-grade and second-grade products, with sibiricose A5, sibiricose A6, polygalaxanthone Ⅲ, 3, 6'-disinapoyl sucrose and tenuifoliside A being identifies as the major differentiate markers.

This study was designed to investigate the effect on tumor growth inhibition activity of lizards (Gekkoswinhonis Guenther) with different extent of broiling. Samples were prepared by a traditional drying method combined with broiling on clay tiles. Four groups of samples were all dried before broiling. Group A was without broiling; group B was mildly broiled; group C was moderately broiled; and group D was heavily broiled. Crispiness was detected by the sizes of the generated fragments of different groups and crispiness increased with broiling. Sensory evaluation of vision and olfaction was performed, and scores were generated by evaluators. Moderately broiled group had the highest total score in sensory evaluation. Water content and content of water-soluble extracts were detected according to Chinese Pharmacopoeia. With the increasing broiling extent, content of water-soluble extracts increased while water content decreased. Soluble protein concentration was detected by bicinchoninic acid (BCA) kit and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with the same crude drug content. Soluble protein concentration decreased with the increasing broiling extent. With equal loading of proteins at the same concentration, soluble protein diversity was detected by SDS-PAGE. Band difference was marked by red boxes. Soluble protein molecule weights showed significant difference with the increasing broiling extent. H₂₂ tumor-bearing mice model was established and used to detect tumor growth inhibition rate and immune organ index. Life quality of mice was evaluated. Mice treated with Gekkoswinhonis Guenther had better appetites and higher average weights compared with positive control group treated with fluorouracil (5-FU). Animal experiments were approved by the Ethics Committee of Beijing University of Chinese Medicine. Group A had the highest tumor growth inhibition rate (34.11%), followed by Group B (29.14%) and Group D (28.43%), Group C (21.98%) had the lowest tumor growth inhibition rate, but sensory evaluation was on the contrary. These results indicated that moderately broiling improved sensory evaluation but reduced the tumor growth inhibition activity of Gekkoswinhonis Guenther. The best tumor growth inhibition activity appeared when water content was 7.71%.

Wu-tou decoction (WTD) was originally recorded in the synopsis of the golden chamber and it had been widely used for the treatment of neuropathic pain (NP) with exact therapeutic efficacy. However, the underlying molecular mechanisms still remain unclarified. Thus, in this research, we aimed at clarifying the underlying molecular mechanisms of WTD against NP by combining network analysis and experimental validation based on the spinal nerve ligation (SNL) model. Firstly, the network analysis indicated that key targets of WTD were significantly involved in the MAPK signaling pathway (P=4.04E-12) and four important components of the above pathway, AKT kinase (AKT), MAP kinase kinase 4 (MKK4), c-Jun N-terminal kinase (JNK) and transcription factor AP-1 (JUN) had been reported to play a vital role in neuroinflammation during the disease process of NP. Then, experimental validation results proved that WTD markedly reduce the severity of mechanical allodynia (P < 0.01) and cold hypersensitivity (P < 0.05) of SNL rats. In addition, Western blot results provided evidence that the phosphorylated protein expression levels of AKT, MKK4, JNK and JUN in the superficial lamina of spinal cord of SNL rats were markedly increased (P < 0.001), and WTD could improve the phosphorylated protein expression level of AKT (P < 0.001) which was reported to be nerve protective and attenuate the phosphorylated protein expression levels of MKK4, JNK and JUN (P < 0.01) which were closely involved into neuroinflammation. In conclusion, this study indicated that WTD might exert anti-hyperalgesia action through the inhibition of neuroinflammation mediated by AKT-MKK4-JNK-JUN which belong to the MAPK signaling pathway. These findings also provided scientific evidences that WTD might be a promising candidate for NP. Animal experiments in this study were approved by the Ethics Committee of Experimental Animals of the China Academy of Chinese Medical Sciences.