New chemical structures and liver-protective activity of the diterpenoids from Callicarpa rubella.

Callicarpa rubella is a characteristic folk herb in the genus Callicarpa, and has abundant ethnobotanical usage as indigenous medicine in Lingnan area of P. R. China. However, the phytochemical and pharmacological properties of C. rubella was rarely investigated. Now, three new diterpenoids, named rubellapene A-C (1-3), along with five known analogues (4-8), were isolated from C. rubella. Their structures were determined by spectroscopic methods, quantum chemical electronic circular dichroism calculations and single-crystal X-ray diffraction analysis. Notably, the norditerpenoids C18 of clerodane type (rubellapene B) was rarely found in the genus Callicarpa. The liver protective effects of all of the isolates (1-8) were evaluated by the changes of cell viability and transaminase content of AST and ALT in H2O2-induced BRL cells. Compound 1, 3-8 exhibited that potent liver protective effects at different levels.

Landscape Changes and Optimization in an Ecological Red Line Area: A Case Study in the Upper Reaches of the Ganjiang River.

The key to optimizing ecological management is to study the spatial configuration of the landscape and the dynamic changes and their driving mechanisms at the landscape scale. The ecological red line area in the hilly area of the upper reaches of the Ganjiang River was chosen as the research area in this study. Based on the theory of landscape ecology and the evolution of biological communities, a multiscale coupling model was adopted and combined with remote sensing (RS) and geographical information system (GIS) technologies to systematically study the evolution of key landscape ecosystems such as forests, patch characteristics, and changes in diversity. The study revealed that: (1) forests represented the largest proportion in the study area, followed by croplands and grasslands; (2) the biological community tended to progress toward climax between 1986 and 1995, but then it moved toward regressive successions between 1995 and 2005 before recovering; (3) the study area was characterized by a high proportion of dominant ecosystems, most of which were at their climax with stable ecological species groups, and which were connected by ecological corridors; and (4) during the period from 1995 to 2010, most landscapes showed a trend of fragmentation. However, during the period from 2010 to 2018, the forest patches were gradually connected. The proportion of dominant landscapes increased, and the landscape uniformity was reduced. Based on the findings, we proposed an ecosystem management strategy that includes strengthening crop management, focusing on the natural restoration of the ecosystems and the cultivation of large patches, exploring disturbances due to mining activities, and applying methods to mitigate damage to and optimize the ecosystem.

Changes in rheumatoid arthritis under ultrasound before and after sinomenine injection.

BACKGROUND: Rheumatoid arthritis (RA) is a prevalent clinical autoimmune disease that is commonly treated with diclofenac and methotrexate. In recent years, the application of traditional Chinese medicine in RA has received widespread attention; it promotes blood circulation, strengthens the immune system, and eliminates evil. The sinomenine preparation of Zhingqeng Fengtongning is studied as a possible treatment for patients with RA. AIM: To explore the value of sinomenine injection into the articular cavity for the treatment of RA. METHODS: A total of 94 patients with RA treated from January 2019 to January 2021 were selected and divided into the study and control groups with 47 patients each using a simple random number table method. Both groups received conventional treatment with diclofenac sodium and methotrexate tablets. The control group received diproxone and lidocaine by intra-articular administration while the study group received an intra-articular administration of the sinomenine preparation of Zhengqing Fengning and lidocaine. χ 2 test was used to evaluate the therapeutic effect and synovial thickness, degree of pain through the visual analog scale (VAS), blood flow grade, arthroinflammatory indexes [rheumatoid factor (RF), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR)] before and after treatment in the two groups. RESULTS: The total effective rate of the study group (93.62%) was higher than that of the control group (78.72%) (P < 0.05). Before treatment, there were no significant differences between the two groups in terms of synovial thickness, VAS score, blood flow grading, levels of RF, and ESR (P > 0.05). After treatment, the synovial thickness and VAS score were significantly lower (P < 0.05) in the study group than in the control group (2.05 ± 0.59 mm vs 2.87 ± 0.64 mm and 2.11 ± 0.62 vs 2.90 ± 0.79 scores, respectively). The rate of blood flow at grade 0 in the study group (76.60%) was higher than that in the control group (57.45%), and the rate of blood flow at grade I (10.64%) was lower than that in the control group (31.91%) (P < 0.05). Furthermore, the levels of RF (55.61 ± 6.13 U/mL), CRP (11.43 ± 3.59 mg/L), and ESR (29.60 ± 5.56 mm/h) in the study group were lower than those in the control group (73.04 ± 9.23 U/mL, 15.07 ± 4.06 mg/L, 36.64 ± 6.10 mm/h, respectively) (P < 0.05). CONCLUSION: Sinomenine administration of Zhengqing Fengtongning in the articular cavity with conventional treatment of RA can improve ultrasonographic blood flow and synovial thickness, reduce pain, regulate inflammation, and enhance therapeutic effect.

Syn-2, 3-diols and anti-inflammatory indole derivatives from Streptomyces sp. CB09001.

Two new natural diols, (2S, 3S, 4S)-4-methyl-1-phenylhexane-2,3-diol (1) and (2S, 3S)-4-methyl-1-phenylpentane-2,3-diol (2), together with five known compounds, xenocyloins B-D (3-5), lumichrome (6) and thymidine (7) were isolated from Streptomyces sp. CB09001. The absolute configurations of 1 and 2 were established by crystallographic structure analysis. The anti-inflammatory effects of 1-7 were also investigated in RAW246.7 murine macrophage cells stimulated by lipopolysaccharide. The indole derivative xenocyloin B (3) significantly inhibited inducible nitric oxide synthase expression in RAW264.7 cells and could be a potential anti-inflammatory drug lead.

Natural phenylethanoid glycosides isolated from Callicarpa kwangtungensis suppressed lipopolysaccharide-mediated inflammatory response via activating Keap1/Nrf2/HO-1 pathway in RAW 264.7 macrophages cell.

ETHNOPHARMACOLOGICAL RELEVANCE: Callicarpa kwangtungensis, as a characteristic traditional herb in China, has been widely used as indigenous medicine for thousands of years in the treatment of upper respiratory tract infection, tonsillitis, pneumonia and traumatic bleeding in China. Phenylethanoid glycosides (PhGs), as natural polyphenols, are especially abundant in this herb and can be regarded as the representative active ingredients in C. kwangtungensis. AIM OF THIS STUDY: This study was performed to investigate the anti-inflammatory pharmacodynamic basis of six PhGs (acteoside, forsythoside B, poliumoside, alyssonoside, parvifloroside A, and syringalide A 3'-α-L-rhanmnopyranoside) isolated from C. kwangtungensis from the perspective of antioxidation. MATERIALS AND METHODS: Six PhGs were isolated from the anti-inflammatory extracts of C. kwangtungensis by various chromatographic techniques and their anti-inflammatory activity on RAW 264.7 murine macrophages induced by LPS was investigated by measuring the release of tumor necrosis factor (TNF-α), the colonic interleukin-6 (IL-6), nitric oxide (NO) and reactive oxygen species (ROS). Further, the underlying anti-inflammatory mechanism of two PhGs (forsythoside B and alyssonoside) was explored by determining the expression of Kelch-like ECH-association protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (OH-1) and quinone oxidoreductase 1 (NQO1). Besides, molecular simulation was also employed to evaluate the binding capacity of two PhGs with Keap1. RESULTS: Compared with the model group, six PhGs revealed obviously inhibitory effects on TNF-α, IL-6, NO and the generation of ROS in RAW 264.7 macrophages. Moreover, forsythoside B and alyssonoside could act as the inhibitors of Keap1-Nrf2 interaction, then activated the nuclear translocation of Nrf2 and promoted the upregulated protein expression of HO-1 and NQO1, finally suppressed LPS-induced inflammatory response in RAW 264.7 macrophages. Molecular modeling exhibited hydrogen bonds played a crucial role for the binding of PhGs with the Nrf2 binding site in Keap1 protein. CONCLUSIONS: Natural PhGs-induced protection against LPS-induced inflammatory response via activating Keap1/Nrf2/HO-1 signaling pathway in RAW 264.7 macrophages were confirmed, which provided experimental and theoretical basis for the deeper use of C. Kwangtungensis in the treatment and prevention of diseases related to inflammation and oxidative stress.

Quantitative imaging of intraerythrocytic hemozoin by transient absorption microscopy.

Hemozoin, the heme detoxification end product in malaria parasites during their growth in the red blood cells (RBCs), serves as an important marker for diagnosis and treatment target of malaria disease. However, the current method for hemozoin-targeted drug screening mainly relies on in vitro ß-hematin inhibition assays, which may lead to false-positive events due to under-representation of the real hemozoin crystal. Quantitative in situ imaging of hemozoin is highly desired for high-throughput screening of antimalarial drugs and for elucidating the mechanisms of antimalarial drugs. We present transient absorption (TA) imaging as a high-speed single-cell analysis platform with chemical selectivity to hemozoin. We first demonstrated that TA microscopy is able to identify ß-hematin, the artificial form of hemozoin, from the RBCs. We further utilized time-resolved TA imaging to in situ discern hemozoin from malaria-infected RBCs with optimized imaging conditions. Finally, we quantitatively analyzed the hemozoin amount in RBCs at different infection stages by single-shot TA imaging. These results highlight the potential of TA imaging for efficient antimalarial drug screening and drug mechanism investigation.

[Evolutionary process unveiled by the maximum genetic diversity hypothesis].

As two major popular theories to explain evolutionary facts, the neutral theory and Neo-Darwinism, despite their proven virtues in certain areas, still fail to offer comprehensive explanations to such fundamental evolutionary phenomena as the genetic equidistance result, abundant overlap sites, increase in complexity over time, incomplete understanding of genetic diversity, and inconsistencies with fossil and archaeological records. Maximum genetic diversity hypothesis (MGD), however, constructs a more complete evolutionary genetics theory that incorporates all of the proven virtues of existing theories and adds to them the novel concept of a maximum or optimum limit on genetic distance or diversity. It has yet to meet a contradiction and explained for the first time the half-century old Genetic Equidistance phenomenon as well as most other major evolutionary facts. It provides practical and quantitative ways of studying complexity. Molecular interpretation using MGD-based methods reveal novel insights on the origins of humans and other primates that are consistent with fossil evidence and common sense, and reestablished the important role of China in the evolution of humans. MGD theory has also uncovered an important genetic mechanism in the construction of complex traits and the pathogenesis of complex diseases. We here made a series of sequence comparisons among yeasts, fishes and primates to illustrate the concept of limit on genetic distance. The idea of limit or optimum is in line with the yin-yang paradigm in the traditional Chinese view of the universal creative law in nature.