Leojaponin inhibits NLRP3 inflammasome activation through restoration of autophagy via upregulating RAPTOR phosphorylation.

ETHNOPHARMACOLOGICAL RELEVANCE: Duan Teng Yimu decoction is a Chinese herbal medicine compound with proven therapeutic effects on inflammasome-related diseases, such as rheumatoid arthritis. This decoction consists of three Chinese herbal medicines, including Leonurus japonicus (L. japonicus), which promotes the blood circulation and exhibits detumescence activity, traditionally curing gynecologic and inflammasome diseases. AIM OF THE STUDY: To explore the anti-inflammasome activity and the underlying mechanisms of action of the compounds from L. japonicus. MATERIALS AND METHODS: A series of compounds were isolated from L. japonicus. Their anti-inflammasome activities were evaluated in macrophages that were co-stimulated by lipopolysaccharide (LPS) and NLRP3 inflammasome inducers. NLRP3 inflammasome formation and apoptosis speck like containing a CARD (ASC) oligomerization were evaluated by immunofluorescent microscopy and Western blot analysis. The regulation of autophagy after treatment of this compound was also evaluated. Lastly, in vivo activity of Leojaponin was analyzed in a mouse acute gouty arthritis model. RESULTS: Here we show that Leojaponin, a diterpenoid compound from L. japonicus, suppressed lactate dehydrogenase and IL-1ß release in Nigericin-stimulated macrophages in a pyroptosis model. Leojaponin inhibits NLRP3 inflammasome activation in both J774A.1 cells and bone marrow-derived macrophages in a dose dependent manner. Moreover, Leojaponin suppressed NLRP3-mediated ASC specks formation and ASC oligomerization. These activities of Leojaponin depend on restoration of autophagy via promoting RAPTOR phosphorylation. Furthermore, Leojaponin ameliorated monosodium urate (MSU)-induced acute gouty arthritis in vivo. CONCLUSION: Our findings suggest that Leojaponin inhibits NLRP3 inflammasome activation through enhancing autophagy via RAPTOR phosphorylation, thereby highlighting Leojaponin as a potent drug for inflammasome-related diseases.

Highly oxygenated lanostane-type triterpenoids and their bioactivity from the fruiting body of Ganoderma gibbosum.

Eight new highly oxygenated lanostane triterpenes, gibbosic acids A-H (1-8), along with three known ones (9-11), were isolated from the fruiting body of Ganoderma gibbosum. The structures of new isolates were assigned by NMR and HRESIMS experiments. The absolute configurations of 1 were further confirmed by single crystal X-ray diffraction data and computational ECD methods. Immunoregulatory effect and anti-inflammatory activities of these compounds were screened in murine lymphocyte proliferation assay and in lipopolysaccharide (LPS)-stimulated RAW-264.7 macrophages, respectively. Compound 2 exhibited immunostimulatory effect both in lymphocyte proliferation assay without any induction and ConA-induced mitogenic activity of T-lymphocyte, and the proportion of lymphocyte proliferation at the concentration of 0.1µM are 20.01% and 21.40%, respectively.

Two new phenolic compounds from the seeds of Machilus yunnanensis.

Chemical constituents investigation on the seeds of Machilus yunnanensis led to two new phenolic compounds 8-O-acetyl-phenylethanoid-4-O-ß-D-glucopyranoside (1) and (E)-2,3-bis(4-hydroxyphenyl)acrylaldehyde (2), together with 16 known compounds. Their structures were elucidated on the basis of spectroscopic data analysis (IR, MS, 1D, and 2D NMR). Meanwhile, compounds 1-3, 6-13, 17, and 18 were evaluated for vasorelaxant effects on the rat endothelium-intact thoracic aorta rings precontracted with phenylephrine (PE) or KCl. The bioassay results showed that compound 17 had significant vasorelaxant effect on the endothelium-intact thoracic aorta rings precontracted with KCl.

Effect of vitamin D on clinical and biochemical parameters in polycystic ovary syndrome women: A meta-analysis.

AIM: Using a meta-analysis framework, we investigated the association between the serum level of vitamin D and the risk of polycystic ovary syndrome (PCOS) and further examined the therapeutic effect of vitamin D on the clinical features of PCOS. MATERIAL AND METHODS: Multiple databases were searched to retrieve studies. We chose clinical studies that investigated the relation between the serum level of vitamin D and the risk of PCOS or the therapeutic effect of vitamin D on PCOS. The search results were screened according to strict inclusion and exclusion criteria to select high-quality studies for inclusion. Statistical analyses were carried out using stata 12.0. RESULTS: Seventeen studies were eligible in this meta-analysis. The levels of 25-hydroxyvitamin D and the quantitative insulin-sensitivity check index in the PCOS group were remarkably lower than in the controls, whereas the homeostasis model assessment of insulin resistance in the PCOS group was markedly higher than in the controls. No statistically significant difference was observed in serum parathyroid hormone levels between the two groups. The 25-hydroxyvitamin D levels were significantly elevated after PCOS patients received vitamin D3 treatment, but serum parathyroid hormone concentration, homeostasis model assessment of insulin resistance and quantitative insulin-sensitivity check index did not show any significant changes, indicating a lack of therapeutic response. CONCLUSION: Our results suggest that the serum level of vitamin D is associated with the risk of PCOS, but the therapeutic effect of vitamin D on PCOS remains to be further explored.

Optimizing ultrasonic ellagic acid extraction conditions from infructescence of Platycarya strobilacea using response surface methodology.

The infructescence of Platycarya strobilacea is a rich source of ellagic acid (EA) which has shown antioxidant, anticancer and antimutagen properties. Response surface methodology (RSM) was used to optimize the conditions for ultrasonic extraction of EA from infructescence of P. strobilacea. A central composite design (CCD) was used for experimental design and analysis of the results to obtain the optimal processing parameters. The content of EA in the extracts was determined by HPLC with UV detection. Three independent variables such as ultrasonic extraction temperature (°C), liquid:solid ratio (mL/g), and ultrasonic extraction time (min) were investigated. The experimental data obtained were fitted to a quadratic equation using multiple regression analysis and also analyzed by appropriate statistical methods. The 3-D response surface and the contour plots derived from the mathematical models were applied to determine the optimal conditions. The optimum ultrasonic extraction conditions were as follows: ultrasonic extraction temperature 70 °C, liquid:solid ratio 22.5, and ultrasonic extraction time 40 min. Under these conditions, the experimental percentage value was 1.961%, which is in close agreement with the value predicted by the model.

[Effect of resveratrol on heart function of rats with adriamycin-induced heart failure].

OBJECTIVE: To observe the protective effects of resveratrol (RES) on the heart function of the rats with adriamycin-induced heart failure. METHOD: Thirty adult male SD rats were randomly divided into 5 groups: normal control (NC) group, adriamycin (ADR) group, RESL + ADR group, RES(H) + ADR group and RES group. RES of 30, 120, 120 mg x kg(-1) x d(-1) was given intraperitoneally (ip) once a day for 3 days in RES(L) + ADR group, RES(H) + ADR group and RES group respectively. The other two groups were given the same amount of normal saline the same way. On the 4h day,ADR of 10 mg x kg(-1) was given intraperitoneally once to induce myocardium injury model. After twenty-four hours, the pathological and biochemical changes of the myocardium were examined. RESULT: As compared with NC group, the MDA, NO and NOS of the ADR group were significantly higher (P < 0.05), and the SOD of the ADR group were markedly lower (P < 0.05). As compared with ADR group, the indexes in RES(L) + ADR group, RES(H) + ADR group were exactly opposing, and took on dose dependance (P < 0.05). Light microscopic morphometry of the heart samples of the rats in ADR + RES(L, H) groups revealed typical diminishing of damage. CONCLUSION: RES can relieve the toxic effects of ADR on myocardium, and the cardioprotective effects may be correlated with its antioxidant activity and downregulation of NO.

[Chinese traditional medicine yi kang ling to treat immunity infertility caused by anti-sperm antibody: the experimental research. I].

OBJECTIVE: To observe the effects of Chinese traditional medicine Yi Kang Ling (YKL) on immunity infertility caused by anti-sperm antibodies (AsAb). METHODS: Based on the animal model of immunity infertility, seventy-five pairs of New Zealand rabbits were divided into three groups: YKL treatment group (sub-divided into mini-, midi- and maxi-dosage groups), prednisone treatment group and non-treatment group. Five pairs of normal rabbits were used as control. The AsAb from the rabbit serum were detected on the 15th, 30th and 45th day of treatment respectively. The sperm density, activity, the mobility and AsAb of seminal plasma from the obedient rabbits were determined. RESULTS: Statistics showed that on the 45th day in mini- and maxi-YKL and prednisone treatment groups the positive serum AsAb reversing ratio reached 100%, and the seminal plasma AsAb reversing ratios were 85% in mini- and maxi-YKL group, 83% in midi-YKL and prednisone groups, while in non-treatment group the reversing ratios of the positive serum AsAb and seminal plasma AsAb were only 20% and 25% respectively. There were also remarkable differences (P < 0.05) in both serum AsAb and seminal plasma AsAb on the 45th day of treatment between YKL, prednisone treatment groups and the non-treatment group. CONCLUSIONS: YKL can effectively reverse the AsAb positive results, hence increasing sperm mobility and improving sperm quality.

[Chinese traditional medicine yi kang ling to treat immunity infertility caused by anti-sperm antibody: the experimental research II].

OBJECTIVE: To observe the effects of Chinese traditional medicine Yi Kang Ling (YKL) on immunity infertility caused by anti-sperm antibodies (AsAb). METHODS: With the AsAb infertile rabbit as the experimental model, seventy-five pairs of New zealand rabbits were divided into three group including YKL treatment group (sub-divided into mini-, midi- and maxi-dosage groups), prednisone treatment group and non-treatment group. Rabbits of the YKL treatment sub-groups were further divided into M+F- (male positive, female negative), M-F+, (male negative, female positive) and M+F+ (male positive, female positive) pairs according to their initial AsAb detection results. The control group consisted of five pairs of normal rabbits. When the expected AsAb reversing ratio was achieved, the rabbits were matted and observed for the number of the pregnant and the weight of the newborn. RESULTS: Statistics showed that in M+F- pairs both the midi-dosage of YKL and prednisone treatment groups had fertility, in the mini- and maxi-dosage of YKL treatment groups, 20% of the female rabbits failed to be pregnant, while in the non-treatment group, 60% female rabbits remained sterile. The sterile ratios of the M-F+ pairs in the mini-, midi- and maxi-dosage of YKL and prednisone treatment groups were 0, 20%, 25% and 25%, respectively, while the sterile ratio in the non-treatment M-F+ group was 40%. In M+F+ groups, the sterile ratios of the three YKL sub-groups, prednisone treatment and non-treatment groups were 20%, 20% and 60% respectively. In the control group the sterile ratio was 20%. The weight of the newborn rabbits were around 50 grams with no visible malformation. CONCLUSIONS: YKL can effectively reverse the AsAb positive results, and restore the fertility of female rabbits. Mini-dosage of YKL for 45 days produced the best results and maxi-dosage of YKL had no negative effects on the weight of the newborn rabbit.