Structure-based development of potent and selective type-II kinase inhibitors of RIPK1

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

The Effect of Equine Placental Extract on Anti-inflammatory and Anti-oxidant Activity of the Skin / 日本補完代替医療学会誌

The anti-inflammatory and anti-oxidant effect of equine placental extract (ePE) on epidermal keratinocytes was examined. ePE reduced mRNA levels of TNF-α (Tumor Necrosis Factor-α) and IL-6 (Interleukin-6) among the inflammatory cytokines released by epidermal keratinocytes after ultraviolet light (UVB: 290-320 nm) exposure. ePE also activated Nrf2, a transcription factor known to be activated by oxidative stress to promote the expression of antioxidant enzymes and suppress inflammation, and it increased the mRNA level of the antioxidant enzyme HO-1 (Heme Oxygenase-1). These results suggest that ePE suppresses UV-induced inflammation of epidermal keratinocytes via activation of Nrf2.

Clinical research progress on drugs for non-alcoholic steatohepatitis treatment / 药学学报

Nonalcoholic steatohepatitis (NASH) is the leading chronic liver disease worldwide. NASH is commonly associated with metabolic risk factors, including obesity, hypertension, and diabetes. Hepatic glucose and lipid metabolism disorder, bile acid toxicity, oxidative stress, inflammation, fibrosis, intestinal dysbacteriosis, and susceptibility gene variation are involved in the pathogenesis of NASH. Drug development for NASH has been slow, this article focuses on the clinical research and development of several promising NASH drugs and their mechanisms, such as drugs targeting gut-liver axis, improving metabolism, inhibiting inflammation and fibrosis.

The neuroprotective effect of salidroside prophylactic administration on MCAO model rats / 中国药理学通报

Aim To investigate the neuroprotective effect of prophylactic administration of salidroside (Sal) on MCAO rats. Methods A total of 52 SD adult male rats were randomly divided into sham operation group (Sham), model group (MCAO) and salidroside pre-administration group (MCAO + Sal). The dose of Sal was 50 mg·kg

The anti-inflammatory mechanism of Aconitum tanguticum based on network pharmacology and molecular docking / 中国药理学通报

Aim To study the potential molecular anti-inflammatory mechanism of Aconitum tanguticum based on network pharmacology methods,molecular docking technology and cell experiment. Methods The active ingredients targets and disease targets of Aconitum tanguticum were collected through literature and database. The common targets were utilized by mixture of them and the core targets were obtained by constructing the protein protein interaction(PPI)network. Then the component-target-disease network diagram was constructed. The gene ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)analysis were performed for common targets. AutoDock Vina(1.1.2)software was utilized for combining some of the core targets and the diterpenoid alkaloids in the chemical components of Aconitum tanguticum. Finally,the influence of alcoholic extract of Aconitum tanguticum(ATS)on RAW264.7 cell inflammation model was preliminarily verified by MTT assay,Griess reagent and realtime RT-PCR. Results A total 17 main active ingredients were obtained from literature and 284 common targets were obtained via intersecting with disease targets. Altogether 108 pathways were screened by KEGG enrichment,mainly including PI3K-Akt,Ras,MAPK and HIF-1. Molecular docking results indicated that the active ingredients of Aconitum tanguticum had a high affinity with the core target to be docked. In vitro experiment suggested that ATS treatment inhibited LPS-induced NO production and iNOS mRNA in RAW264.7 cells. Realtime RT-PCR detection suggested that ATS played an anti-inflammatory effect by regulating the PI3K-Akt signaling pathway. Conclusions Aconitum tanguticum exerts anti-inflammatory effects through PI3K-Akt pathways,which provides the scientific basis for better promoting the development of Aconitum tanguticum.

Summary of anti-inflammatory and antiviral effects of IFIT1 / 中国药理学通报

IFIT1 is a highly inducible member of the interferon stimulating gene family (ISGs) with tetrapeptide repeats. It mainly exists in the cytoplasm and is regulated by interferon, a variety of antiviral role through a variety of mechanisms and pathways, and many viruses have evolved unique mechanisms to evade the limiting effects of IFIT1 and thus counter the body' s antiviral immunity, the unique anti-inflammatory effect of IFIT1 has been extensively studied in inflammatory diseases, Therefore, we mainly review the anti-inflammatory and antiviral effects of IFIT1 and the related mechanisms, so as to provide new therapeutic targets and ideas for the treatment of related diseases.

Research advance in antiviral effect of sophoridine / 中国药理学通报

Sophoridine is a quinolizidine alkaloid extracted from Sophora in legumes, which is one of the main active ingredients of Sophora alopecuroides L, Sophora flavescentis Ait and Sophora davidii (Franch.) skeels. Its molecular formula is C

GLPS improves EAE demyelination through inhibition of TLR4/NF-KB pathway / 中国药理学通报

Aim To explore the protective effects of ganoderma lucidum polysaccharides (GLPS) on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS) and the underlying mechanism. Methods Thirty C57BL/6 mice were randomly divided into three groups: normal control group, EAE model group and GLPS group (5 mg • kg

A new class of potent liver injury protective compounds: Structural elucidation, total synthesis and bioactivity study

A new class of potent liver injury protective compounds, phychetins A-D ( 1- 4) featuring an unique 6/6/5/6/5 pentacyclic framework, were isolated and structurally characterized from a Chinese medicinal plant Phyllanthus franchetianus. Compounds 2- 4 are three pairs of enantiomers that were initially obtained in a racemic manner, and were further separated by chiral HPLC preparation. Compounds 1- 4 were proposed to be originated biosynthetically from a coexisting lignan via an intramolecular Friedel-Crafts reaction as the key step. A bioinspired total synthesis strategy was thus designated, and allowed the effective syntheses of compounds 2- 4 in high yields. Some of compounds exhibited significant anti-inflammatory activities in vitro via suppressing the production of pro-inflammatory cytokine IL-1β. Notably, compound 4, the most active enantiomeric pair in vitro, displayed prominent potent protecting activity against liver injury at a low dose of 3 mg/kg in mice, which could serve as a promising lead for the development of acute liver injury therapeutic agent.

Anti-inflammatory material basis and mechanism of Artemisia stolonifera based on UPLC-Q-TOF-MS combined with network pharmacology and molecular docking / 中国中药杂志

This study aimed to explore the anti-inflammatory material basis and molecular mechanism of Artemisia stolonifera based on the analysis of the chemical components in different extracted fractions of A. stolonifera and their antioxidant and anti-inflammatory effects in combination with network pharmacology and molecular docking. Thirty-two chemical components were identified from A. stolonifera by ultra-performance liquid chromatography coupled to tandem quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Among them, there were 7, 21 and 22 compounds in water, n-butanol and ethyl acetate fractions, respectively. The antio-xidant capacity of different extracted fractions was evaluated by measuring their scavenging ability against 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl(DPPH) and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid)(ABTS) free radicals and total antioxidant capacity [ferric reducing antioxidant power(FRAP) assay]. The inflammatory model of RAW264.7 cells was induced by lipopolysaccharide(LPS), and the levels of nitrite oxide(NO), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) in the supernatant and the mRNA expression of related inflammatory factors in cells were used to evaluate the anti-inflammatory effects. The results revealed that ethyl acetate fraction of A. stolonifera was the optimal antioxidant and anti-inflammatory fraction. By network pharmacology, it was found that flavonoids such as rhamnazin, eupatilin, jaceosidin, luteolin and nepetin could act on key targets such as TNF, serine/threonine protein kinase 1(AKT1), tumor protein p53(TP53), caspase-3(CASP3) and epidermal growth factor receptor(EGFR), and regulate the phosphatidylinositol-3-kinase-protein kinase B(PI3K-AKT) and mitogen-activated protein kinase(MAPK) signaling pathways to exert the anti-inflammatory effects. Molecular docking further indicated excellent binding properties between the above core components and core targets. This study preliminarily clarified the anti-inflammatory material basis and mechanism of ethyl acetate fraction of A. stolonifera, providing a basis for the follow-up clinical application of A. stolonifera and drug development.

Physicochemical properties and anti-inflammatory and immunomodulatory effects of Shengfupian polysaccharides / 中国中药杂志

In this study, the crude polysaccharides was extracted from Shengfupian and purified by Sevag deproteinization. Then, the purified neutral polysaccharide fragment was obtained by the DEAE-52 cellulose chromatography column and Sephadex G-100 co-lumn. The structure of polysaccharides was characterized by ultraviolet spectroscopy, infrared spectroscopy, ion chromatography, and gel permeation chromatography. To investigate the anti-inflammatory activity of Shengfupian polysaccharides, LPS was used to induce inflammation in RAW264.7 cells. The expression of the CD86 antibody on surface of M1 cells, the function of macrophages, and the content of NO and IL-6 in the supernatant were examined. An immunodepression model of H22 tumor-bearing mice was established, and the immunomodulatory activity of Shengfupian polysaccharides was evaluated based on the tumor inhibition rate, immune organ index and function, and serum cytokine levels. Research indicated that Shengfupian polysaccharides(80 251 Da) was composed of arabinose, galactose, glucose, and fructose with molar ratio of 0.004∶0.018∶0.913∶0.065. It was smooth and lumpy under the scanning electron microscope. In the concentration range of 25-200 μg·mL~(-1), Shengfupian polysaccharides exhibited little or no toxicity to RAW264.7 cells and could inhibit the polarization of cells to the M1 type and reduce the content of NO and IL-6 in the cell supernatant. It could suppress the phagocytosis of cells at the concentration of 25 μg·mL~(-1), while enhancing the phagocytosis of RAW264.7 cells within the concentration range of 100-200 μg·mL~(-1). The 200 mg·kg~(-1) Shengfupian polysaccharides could alleviate the spleen injury caused by cyclophosphamide, increase the levels of IL-1β and IL-6, and decrease the level of TNF-α in the serum of mice. In conclusion, Shengfupian polysaccharides has anti-inflammatory effect and weak immunomodulatory effect, which may the material basis of Aconm Lateralis Radix Praeparaia for dispelling cold and relieving pain.

Antioxidant and anti-inflammatory activities of four kinds of Huangshan chrysanthemum / 药学实践杂志

Objective To investigate the antioxidant and anti-inflammatory activities of four kinds of Huangshan chrysanthemum. Methods ABTS, FRAP and DPPH were used to detect the antioxidant activities of Huangshan golden silk chrysanthemum, Huangshan chrysanthemum, Huangshan gongju, and Huangshan dendranthema. Their anti-inflammatory activities were evaluated by NF-κB reporter gene assay and rat foot swelling models. Results The outcomes of ABTS，FRAP and DPPH showed that the water extracts of four kinds of chrysanthemum all had certain antioxidant activities and the activities of Huangshan golden silk chrysanthemum were strongest, followed by Huangshan chrysanthemum , Huangshan gongju , and Huangshan dendranthema. Results of NF-κB reporter gene assay and rat foot swelling models showed that four extracts of chrysanthemum morifolium could inhibit the transcription of NF-κB induced by LPS and alleviate foot swelling of rat induced by carrageenan, with the strongest activity of Huangshan chrysanthemum, followed by Huangshan golden silk chrysanthemum, Huangshan gongju, and Huangshan dendranthema. Conclusion The antioxidant activities of Huangshan golden silk chrysanthemum were strongest, followed by Huangshan chrysanthemum, Huangshan gongju, and Huangshan dendranthema. The anti-inflammatory activities of Huangshan chrysanthemum were strongest, followed by Huangshan golden silk chrysanthemum, Huangshan gongju, and Huangshan dendranthema.

Anti-swelling and Analgesic Mechanism of Jianpi Tongluo Prescription from MAPKs Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the anti-swelling and analgesic effects of Jianpi Tongluo prescription （JPTL） and to explore its mechanism initially. MethodA total of 120 ICR mice were divided into normal group， model group， JPTL low-， medium- and high-dose groups （5， 10， 20 g·kg-1） and positive drug （celecoxib， 0.03 g·kg-1） group， with 10 in each group （po，once a day）. Complete freund's adjuvant （CFA） was used to induce the model of chronic inflammatory pain， and xylene-induced ear swelling test， hot plate test and acetic acid writhing test were performed to observe the anti-swelling and analgesic effects of different doses of JPTL in these four acute and chronic models. Further， enzyme-linked immunosorbent assay （ELISA） was used to detect the expressions of prostaglandin E2 （PGE2）， interleukin-1β （IL-1β）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in serum and inflammatory paw of mice with chronic inflammatory pain， and the expressions of aquaporin 1 （AQP1）， aquaporin 3 （AQP3）， cyclooxygenase 1 （COX1）， cyclooxygenase 2 （COX2） and mitogen-activated protein kinases （MAPKs） in inflammatory paw were detected by Western blot， to explore the preliminary mechanism of JPTL. ResultCompared with the conditions in the normal group， there was a significant increase in the ear swelling of xylene-induced model mice， a shortened paw withdrawal latency in the hot plate test （P<0.01）. Compared with the model group， JPTL remarkably increased the inhibition rate of xylene-induced ear swelling （P<0.05， P<0.01）， prolonged the latency period of writhing caused by acetic acid and reduced the number of writhing （P<0.05， P<0.01）. Compared with normal group, the degree of feet swelling in chronic inflammatory pain mice was significantly increased， the threshold of mechanical pain was decreased and the threshold of cold pain was increased （P<0.05， P<0.01）， the protein contents of AQP1 and AQP3 in inflammatory feet were increased， and the contents of IL-1β， IL-6， TNF-α， PGE2 and COX2 in inflammatory feet were increased in serum and/or inflammatory feet. The protein expression levels of p-p38 MAPK， p-JNK and p-ERK in inflammatory feet were increased （P<0.01）. Compared with the model group， JPTL relieved paw swelling of mice with chronic inflammatory pain， elevated mechanical withdrawal threshold while decreased cold withdrawal threshold， with analgesia lasting for 4 h and the optimal time point for analgesia being 2 h after administration （P<0.05， P<0.01）. Moreover， JPTL down-regulated AQP1， AQP3， COX2， p-p38 MAPK， p-JNK and p-ERK in inflammatory paw of mice with chronic inflammatory pain and reduced IL-1β， IL-6， TNF-α， and PGE2 in serum and/or inflammatory paw， but it had no significant effect on COX1 （P<0.05， P<0.01）. ConclusionJPTL has anti-swelling and analgesic effects， and its mechanism is related to inhibiting the production of cytokines and inflammatory mediators via the down-regulation of MAPKs signaling pathway， which provides an experimental basis for the clinical application of JPTL.

Effect of Component Compatibility of Gentianae Macrophyllae Radix and Clematidis Radix et Rhizoma on Serum Inflammatory Factors and Expression of NF-κB and VEGF in Ankle Joint of Rats with Rheumatoid Arthritis / 中国实验方剂学杂志

ObjectiveTo investigate the anti-inflammatory effect of the component compatibility of Gentianae Macrophyllae Radix and Clematidis Radix et Rhizoma on the rat model of rheumatoid arthritis （RA） and the mechanism. MethodSeventy-two SPF-grade SD rats （male and female） aged 5 to 6 weeks were selected. Except the blank group， the rat model of collagen-induced arthritis （CIA） was replicated by the type Ⅱ collagen induction method. The 64 rats after successfully modeling were randomly divided into model group， methotrexate group （0.375 mg·kg-1）， gentianoside with magnoflorine group （150.454 1 mg·kg-1+5.061 8 mg·kg-1）， gentianoside with clematichinenoside AR group （150.454 1 mg·kg-1+16.433 1 mg·kg-1）， sweroside with magnoflorine group （3.455 8 mg·kg-1+5.061 8 mg·kg-1）， sweroside with clematichinenoside AR group （3.455 8 mg·kg-1+16.433 1 mg·kg-1）， swertiamarin with magnoflorine group （9.303 2 mg·kg-1+5.061 8 mg·kg-1）， and swertiamarin with clematichinenoside AR group （9.303 2 mg·kg-1+16.433 1 mg·kg-1）， with 8 rats in each group. Each group was given the corresponding medicinal solution or normal saline by gavage for 15 d. During the experiment， the general status， of rats in each group were observed and recorded. Tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， rheumatoid factor （RF）， C reactive protein （CRP）， prostaglandin E2 （PGE2）， and anti-cyclic peptide containing citrulline antibody （anti-CCP Ab） in the serum of rats were measured by enzyme-linked immunosorbent assay （ELISA）. The histopathological changes in rat ankle joints were observed by hematoxylin-eosin （HE） staining. Immunohistochemistry （IHC） and Western blot were used to detect the protein expression of nuclear factor-κB （NF-κB） and vascular endothelial growth factor （VEGF） in rat ankle joints. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of NF-κB and VEGF in rat ankle joints. ResultCompared with those in the blank group， rats in the model group were in poor general conditions with significant foot-plantar swelling， and the content of CRP， anti-CCP Ab， and IL-1β in the rat serum was significantly increased （P<0.01）. In the model group， the tissue structure of the ankle joint was severely damaged， and the protein and mRNA expression of NF-κB and VEGF in the rat ankle joints were significantly up-regulated （P<0.01）. As compared with the model group， the general status of rats in each administration group was significantly improved. The levels of serum TNF-α， IL-1β， RF， CRP， PGE2， and anti-CCP Ab were reduced to different degrees in these administration groups， among which the effects of the gentianoside with clematichinenoside AR group on down-regulating serum TNF-α and IL-1β， the gentianoside with magnoflorine group on down-regulating serum RF and CRP， the sweroside with magnoflorine group on down-regulating serum PGE2， and the swertiamarin with clematichinenoside AR group on lowering serum anti-CCP Ab were better than those of administration groups. The histopathological changes in the ankle joint were improved to different degrees. The protein and mRNA expression of NF-κB and VEGF in rat ankle joints in the administration groups was significantly down-regulated （P<0.05， P<0.01）， and the swertiamarin paired with clematichinenoside AR group had the most significant effect. ConclusionThe component compatibility of Gentianae Macrophyllae Radix and Clematidis Radix et Rhizoma exerts a good therapeutic effect on the rat model of RA， and the compatibility of components from the two medicines has a multi-channel， multi-target， and synergistic effect. The five component compatibility patterns， namely gentiobioside with magnoflorine， gentiobioside with clematichinenoside AR， sweroside with clematichinenoside AR， swertiamarin with magnoflorine， and swertiamarin with clematichinenoside AR， all have potential advantages. The mechanism may be related to the reduction of inflammatory factor secretion and the inhibition of abnormal protein and mRNA expression of NF-κB and VEGF.

Chlorella sp.-ameliorated undesirable microenvironment promotes diabetic wound healing

Chronic diabetic wound remains a critical challenge suffering from the complicated negative microenvironments, such as high-glucose, excessive reactive oxygen species (ROS), hypoxia and malnutrition. Unfortunately, few strategies have been developed to ameliorate the multiple microenvironments simultaneously. In this study, Chlorella sp. (Chlorella) hydrogels were prepared against diabetic wounds. In vitro experiments demonstrated that living Chlorella could produce dissolved oxygen by photosynthesis, actively consume glucose and deplete ROS with the inherent antioxidants, during the daytime. At night, Chlorella was inactivated in situ by chlorine dioxide with human-body harmless concentration to utilize its abundant contents. It was verified in vitro that the inactivated-Chlorella could supply nutrition, relieve inflammation and terminate the oxygen-consumption of Chlorella-respiration. The advantages of living Chlorella and its contents were integrated ingeniously. The abovementioned functions were proven to accelerate cell proliferation, migration and angiogenesis in vitro. Then, streptozotocin-induced diabetic mice were employed for further validation. The in vivo outcomes confirmed that Chlorella could ameliorate the undesirable microenvironments, including hypoxia, high-glucose, excessive-ROS and chronic inflammation, thereby synergistically promoting tissue regeneration. Given the results above, Chlorella is considered as a tailor-made therapeutic strategy for diabetic wound healing.

Anti-inflammatory sesquiterpene polyol esters from the stem and branch of Tripterygium wilfordii / 中国天然药物

The stem and branch extract of Tripterygium wilfordii (Celastraceae) afforded seven new dihydroagarofuran sesquiterpene polyesters [tripterysines A-G (1-7)] and eight known ones (8-15). The chemical structures of these new compounds were established based on combinational analysis of HR-ESI-MS and NMR techniques. The absolute configurations of tripterysines A-C (1-3) and E-G (5-7) were determined by X-ray crystallographic analysis and circular dichroism spectra. All the compounds were screened for their inhibitory effect on inflammation through determining their inhibitory effect on nitric oxide production in LPS-induced RAW 264.7 cells and the secretion of inflammatory cytokines TNF-α and IL-6 in LPS-induced BV2 macrophages. Compound 9 exhibited significant inhibitory activity on NO production with an IC50 value of 8.77 μmol·L-1. Moreover, compound 7 showed the strongest inhibitory effect with the secretion of IL-6 at 27.36%.

Injectable hydrogel microspheres experimental research for the treatment of osteoarthritis / 中国修复重建外科杂志

OBJECTIVE@#To prepare a novel hyaluronic acid methacrylate (HAMA) hydrogel microspheres loaded polyhedral oligomeric silsesquioxane-diclofenac sodium (POSS-DS) patricles, then investigate its physicochemical characteristics and in vitro and in vivo biological properties.@*METHODS@#Using sulfhydryl POSS (POSS-SH) as a nano-construction platform, polyethylene glycol and DS were chemically linked through the "click chemistry" method to construct functional nanoparticle POSS-DS. The composition was analyzed by nuclear magnetic resonance spectroscopy and the morphology was characterized by transmission electron microscopy. In order to achieve drug sustained release, POSS-DS was encapsulated in HAMA, and hybrid hydrogel microspheres were prepared by microfluidic technology, namely HAMA@POSS-DS. The morphology of the hybrid hydrogel microspheres was characterized by optical microscope and scanning electron microscope. The in vitro degradation and drug release efficiency were observed. Cell counting kit 8 (CCK-8) and live/dead staining were used to detect the effect on chondrocyte proliferation. Moreover, a chondrocyte inflammation model was constructed and cultured with HAMA@POSS-DS. The relevant inflammatory indicators, including collagen type Ⅱ, aggrecan (AGG), matrix metalloproteinase 13 (MMP-13), recombinant A disintegrin and metalloproteinase with thrombospondin 5 (Adamts5), and recombinant tachykinin precursor 1 (TAC1) were detected by immunofluorescence staining and real-time fluorescence quantitative PCR, with normal cultured chondrocytes and the chondrocyte inflammation model without treatment as control group and blank group respectively to further evaluate their anti-inflammatory activity. Finally, by constructing a rat model of knee osteoarthritis, the effectiveness of HAMA@POSS-DS on osteoarthritis was evaluated by X-ray film and Micro-CT examination.@*RESULTS@#The overall particle size of POSS-DS nanoparticles was uniform with a diameter of about 100 nm. HAMA@POSS-DS hydrogel microspheres were opaque spheres with a diameter of about 100 μm and a spherical porous structure. The degradation period was 9 weeks, during which the loaded POSS-DS nanoparticles were slowly released. CCK-8 and live/dead staining showed no obvious cytotoxicity at HAMA@POSS-DS, and POSS-DS released by HAMA@POSS-DS significantly promoted cell proliferation (P<0.05). In the chondrocyte anti-inflammatory experiment, the relative expression of collagen type Ⅱ mRNA in HAMA@POSS-DS group was significantly higher than that in control group and blank group (P<0.05). The relative expression level of AGG mRNA was significantly higher than that of blank group (P<0.05). The relative expressions of MMP-13, Adamts5, and TAC1 mRNA in HAMA@POSS-DS group were significantly lower than those in blank group (P<0.05). In vivo experiments showed that the joint space width decreased after operation in rats with osteoarthritis, but HAMA@POSS-DS delayed the process of joint space narrowing and significantly improved the periarticular osteophytosis (P<0.05).@*CONCLUSION@#HAMA@POSS-DS can effectively regulate the local inflammatory microenvironment and significantly promote chondrocyte proliferation, which is conducive to promoting cartilage regeneration and repair in osteoarthritis.

Research progress in pharmacological effectsand mechanism of Fel Ursi against cardiovascular and cerebrovascular diseases / 中国中药杂志

Fel Ursi is a dried product obtained from the gallbladder of Ursidae animals, such as Selenarctos thibetanus or Ursus arctos, through gallbladder surgery for bile drainage. It is one of the rare animal medicinal materials in China and is known for its therapeutic effects, including clearing heat, removing toxins, extinguishing wind, relieving spasms, clearing the liver, and improving vision. Research has also found that Fel Ursi has pharmacological effects against cardiovascular and cerebrovascular diseases, such as anti-inflammatory, anti-apoptotic, and antioxidant stress properties. Recently, numerous studies have confirmed the close relationship between cardiovascular and cerebrovascular diseases and the gut microbiota as well as gut metabolites. Fel Ursi contains bile acid components that may have bidirectional regulatory effects on the gut microbiota and gut metabolites. This aspect could represent a potential therapeutic pathway for Fel Ursi in the treatment of cardiovascular and cerebrovascular diseases. This article comprehensively summarized relevant literature in China and abroad, reviewed the research progress on the pharmacological effects of Fel Ursi against cardiovascular and cerebrovascular diseases, and explored the impact of Fel Ursi on gut microbiota and gut metabolites, thereby aiming to provide references for further in-depth research and clinical application of Fel Ursi.

Functional biomaterials for comprehensive periodontitis therapy

Periodontitis is an inflammatory disease caused by bacterial infection directly, and the dysregulation of host immune-inflammatory response finally destroys periodontal tissues. Current treatment strategies for periodontitis mainly involve mechanical scaling/root planing (SRP), surgical procedures, and systemic or localized delivery of antimicrobial agents. However, SRP or surgical treatment alone has unsatisfactory long-term effects and is easy to relapse. In addition, the existing drugs for local periodontal therapy do not stay in the periodontal pocket long enough and have difficulties in maintaining a steady, effective concentration to obtain a therapeutic effect, and continuous administration always causes drug resistance. Many recent studies have shown that adding bio-functional materials and drug delivery systems upregulates the therapeutic effectiveness of periodontitis. This review focuses on the role of biomaterials in periodontitis treatment and presents an overview of antibacterial therapy, host modulatory therapy, periodontal regeneration, and multifunctional regulation of periodontitis therapy. Biomaterials provide advanced approaches for periodontal therapy, and it is foreseeable that further understanding and applications of biomaterials will promote the development of periodontal therapy.

Five new terpenoids from Viburnum odoratissimum var. sessiliflorum / 中国天然药物

Five new terpenoids, including two vibsane-type diterpenoids (1, 2) and three iridoid allosides (3-5), together with eight known ones, were isolated from the leaves and twigs of Viburnum odoratissimum var.sessiliflorum. Their planar structures and relative configurations were determined by spectroscopic methods, especially 2D NMR techniques. The sugar moieties of the iridoids were confirmed as β-D-allose by GC analysis after acid hydrolysis and acetylation. The absolute configurations of neovibsanin Q (1) and dehydrovibsanol B (2) were determined by quantum chemical calculation of their theoretical electronic circular dichroism (ECD) spectra and Rh2(OCOCF3)4-induced ECD analysis. The anti-inflammatory activities of compounds 1, 3, 4, and 5 were evaluated using an LPS-induced RAW264.7 cell model. Compounds 3suppressed the release of NO in a dose-dependent manner, with an IC50 value of 55.64 μmol·L-1. The cytotoxicities of compounds 1-5 on HCT-116 cells were assessed and the results showed that compounds 2 and 3 exhibited moderate inhibitory activities with IC50 values of 13.8 and 12.3 μmol·L-1, respectively.