[Mechanism of tetramethylpyrazine attenuates inflammatory injury in endothelial cells by activating the SIRT1 signaling pathway]. / 川芎嗪通过激活SIRT1ä¿¡å·é€šè·¯å‡è½»å† çš®ç»†èƒžç‚Žç—‡æŸä¼¤çš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To study the effects and mechanisms of tetramethylpyrazine (TMP) on tumor necrosis factor-α (TNF-α)-induced inflammatory injury in human coronary artery endothelial cells (HCAEC). METHODS: HCAEC were randomly divided into four groups: the control group (no treatment), the model group (treated with TNF-α, 50 ng/mL for 24 hours), the TMP group (pre-treated with TMP, 80 µg/mL for 12 hours followed by TNF-α treatment for 24 hours), and the SIRT1 inhibitor group (pre-treated with TMP and the specific SIRT1 inhibitor EX527 for 12 hours followed by TNF-α treatment for 24 hours). Cell viability was assessed using the CCK-8 method, lactate dehydrogenase (LDH) activity was measured using an LDH assay kit, reactive oxygen species (ROS) levels were observed using DCFH-DA staining, expression of pyroptosis-related proteins was detected by Western blot, and SIRT1 expression was analyzed using immunofluorescence staining. RESULTS: Compared to the control group, the model group showed decreased cell viability, increased LDH activity, ROS level and expression of pyroptosis-related proteins, and decreased SIRT1 expression (P<0.05). Compared to the model group, the TMP group exhibited increased cell viability, decreased LDH activity, ROS level and expression of pyroptosis-related proteins, and increased SIRT1 expression (P<0.05). In comparison to the TMP group, the SIRT1 inhibitor group showed decreased cell viability, increased LDH activity, ROS level and expression of pyroptosis-related proteins, and decreased SIRT1 expression (P<0.05). CONCLUSIONS: TMP may attenuate TNF-α-induced inflammatory injury in HCAEC, which is associated with the inhibition of pyroptosis and activation of the SIRT1 signaling pathway.

Progress of researches on mechanisms of acupuncture therapy in the treatment of lumbar disc herniation. / é’ˆç¸æ²»ç–—è °æ¤Žé—´ç›˜çªå‡ºç—‡ä½œç”¨æœºåˆ¶ç ”ç©¶è¿›å±•.

Lumbar intervertebral disc herniation (LDH) is a common and frequently-occurring disease, which usually causes lumbar and leg pain. Studies have shown that acupuncture can improve the symptoms of LDH patients. In the present paper, we summarize the progress of researches on the mechanisms of acupuncture underlying improvement of symptoms of LDH in recent 10 years from 1) delaying the intervertibral disc degeneration (by down-regulating the expressions of matrix metalloproteinase ï¼»MMPï¼½-3 and MMP-4, up-regulating the expressions of diosaccharides and polyglycoprotein, inhibiting apoptosis and promoting mitochondrial autophagy of nucleus pulposus cells, etc.), 2) maintaining spinal column stability (by relieving rachiasmus and improving lumbar flexor and extensor muscle strength, lowering the degree of polyfidus edema and fat infiltration, and restoring the biomechanics of the spine), 3) regulating inflammation (by inhibiting the production of proinflammatory factors and increasing the production of anti-inflammatory factors, etc.), 4) regulating immune response (by promoting the activity of T cells and other immune cells, lowering serum levels of MMP-3, transforming growth factor-ß1 and prostaglandin E2, raising serum levels of IgA, IgG and IgM to improve immune function ), 5) modulating neural structure and function (by promoting myelin regeneration of sciatic nerve fibers, and reducing the edema of Schwann cells' cytoplasm and mitochondria, and improving neural ultrastructure, and sensory and motor functions of peripheral nerves, etc.), 6) relieving lumbar pain (by down-regulating expression of Ca2+/calmodulin-dependent protein kinase and activation of lumbar spinal cord glial cells, blocking nociceptive signal conduction, regulating the levels of pain-related factors, etc.), and 7) improving local microcirculation. These results may provide scientific evidence for acupuncture treatment of LDH.

Iboga-type alkaloids with Indolizidino[8,7-b]Indole scaffold and bisindole alkaloids from Tabernaemontana bufalina Lour.

Phytochemical investigation on the aerial parts of Tabernaemontana bufalina Lour. (Apocynaceae) led to the identification of four undescribed monoterpenoid indole alkaloids named taberbufamines A-D, an undescribed natural product, and fourteen known indole alkaloids. The structures of the undescribed alkaloids were established by spectroscopic and computational methods, and their absolute configurations were further determined by quantum chemical TDDFT calculations and the experimental ECD spectra. Taberbufamines A and B possessed an uncommon skeleton incorporating an indolizidino [8,7-b]indole motif with a 2-hydroxymethyl-butyl group attached at the pyrrolidine ring. Biosynthetically, Taberbufamines A and B might be derived from iboga-type alkaloid through rearrangement. Vobatensine C showed significant bioactivity against A-549, Bel-7402, and HCT-116 cells with IC50 values of 2.61, 1.19, and 1.74 µM, respectively. Ervahanine A showed antimicrobial activity against Bacillus subtilis, Mycobacterium smegmatis, and Helicobacter pylori with MIC values of 4, 8, and 16 µg/mL, respectively. 19(S)-hydroxyibogamine was shown as butyrylcholinesterase inhibitor (IC50 of 20.06 µM) and α-glycosidase inhibitor (IC50 of 17.18 µM), while tabernamine, ervahanine B, and ervadivaricatine B only showed α-glycosidase inhibitory activities with IC50 values in the range of 0.95-4.61 µM.

Octahydro-Protoberberine and Protoemetine-Type Alkaloids from the Stems of Alangium salviifolium and Their Cytotoxicity.

Two octahydro-protoberberine alkaloids, alangiifoliumines A (1) and B (2), and two new protoemetine derivatives, alangiifoliumines C (3) and D (4), together with 11 known compounds, have been isolated from the stems of Alangium salviifolium. While the structures of these compounds were elucidated by spectroscopic methods, the absolute configurations of the new alkaloids were determined by conformational analysis and time-dependent density functional theory-electronic circular dichroism spectra calculations on selected stereoisomers. Compounds 1 and 2 represent the first 5,8,8a,9,12,12a,13,13a-octahydro-protoberberine derivatives, in which the aromatic ring D was reduced to cyclohexene. All the compounds isolated were evaluated for their cytotoxic activity against three human cancer cell lines: A-549, HeLa, and SKOV-3. Alkaloids 1, 3, and 6-14 exhibited inhibitory effects against all three human cancer cell lines, with half-maximal inhibitory concentration (IC50) values in the range of 3 nM to 9.4 µM.