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Introduction Piperlongumine (PL) is a bioactive alkaloid and medicinal compound of piperamide isolated from the long pepper (Piper longum Linn). It has demonstrated bactericidal action against Mycobacterium tuberculosis (MTB), the cause of pulmonary tuberculosis; nevertheless, immunomodulatory activity had not been identified for it in MTB-triggered granulomatous inflammation. This study investigated if piperlongumine could inhibit such inflammation. Material and Methods Mycobacterium tuberculosis strain H37Rv was subjected to a broth microdilution assay. Piperlongumine at 5, 15, and 25 μg/mL, 0.2% dimethyl sulphoxide as control or 4 μM of dexamethasone were tested in vitro on MH-S murine alveolar macrophages. BALB/c mice were orally administered PL at 50, 100 and 150 mg/kg b.w. after trehalose-6,6-dimycolate (TDM) stimulation. Chemokine and cytokine concentrations were determined in lung supernatants. Flow cytometry and Western blot analysis were performed to determine phosphorylated spleen tyrosine kinase (Syk), c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways. Results Piperlongumine inhibited inflammatory mediators and adherence of lymphocyte function-associated antigen 1 to MH-S cells following TDM activation. It also improved macrophage clearance of MTB. In TDM-stimulated MH-S cells, PL significantly influenced the macrophage inducible Ca2+-dependent lectin receptor (Mincle)-Syk-ERK signalling pathway. Oral dosing of PL effectively suppressed the development of pulmonary granulomas and inflammatory reactions in the TDM-elicited mouse granuloma model. Conclusion PL as an inhibitor of MTB-triggered granulomatous inflammation may be an effective complementary treatment for mycobacterial infection.

Seasonal hypoxia in water bodies can increase levels of reduced chemical species in the hypolimnion as they are released from anoxic bottom sediments. Water-lifting aeration (WLA) is a technology known to solve this problem by elevating near-sediment dissolved oxygen (DO) and increasing mixing in the water column in a canyon reservoir with deep water (>20 m). The influence of WLA in reservoirs with large surface area and small water depth has not been adequately evaluated. For this purpose, the efficiency of an innovative WLA system was reviewed in Zhoucun Reservoir (ZCR), a mildly eutrophic reservoir with a mean depth of 15 m. Three years of field experiment was performed in ZCR. Water and sediment samples were collected before and after the operation of the WLA system to explore the causes for the deterioration of water quality in ZCR, and the efficiency of the innovative WLA system installed in 2015. With the use of a microporous aerator and a kinetic energy dissipator, the new-style WLA system is different from WLA studied before. As a result of thermal stratification and the long duration of anaerobic environment in the hypolimnion, the sediment oxygen consumption rate in ZCR was calculated to be 16.14 mg m−2 h−1, which was much higher than other reservoirs, and the main pollutants in ZCR were ammonia, phosphorus, manganese and sulphide. After the operation of the new WLA system, the anaerobic environment in the bottom water was completely reversed and the DO concentration in the hypolimnion water has been maintained at more than 6 mg L−1. The release of pollutants from sediments, such as ammonia, phosphorus, manganese and sulphide, was inhibited significantly. Ammonia, phosphorus, manganese and sulphide in water decreased by 89%, 84%, 97% and 87%, respectively. The results of this study demonstrate that employing WLA systems to oxygenate and mix stagnant water bodies is a viable and potentially favourable management strategy for reservoirs with large surface area and relatively small water depth.

Four new cimiacerol-type triterpenoids (1-4), together with three unreported tetranor-cycloartane derivatives (5–7), were isolated from the roots of Cimicifuga foetida. Their structures were elucidated via analysis of spectroscopic and chemical reaction data. The inhibitory effects of the isolated compounds on the mRNA expression of atherosclerosis-related factors CD147 (extracellular matrix metalloproteinase inducer, EMMPRIN), matrix metalloproteinase 2 (MMP-2) and MMP-9 were evaluated by using quantitative real-time PCR (q-PCR) in phorbol-12-myristate-13-acetate (PMA)-induced human monocytic THP-1 cells. All tested compounds were inactive, except the aglycone, compound 4, which dose-dependently (10 μM to 50 μM) suppressed the mRNA expression of CD147, MMP-2, and MMP-9. In addition, the migration of the induced THP-1 cells was also strongly and dose-dependently inhibited by 4.

Eleven new 9,19-cycloartane triterpenes (1–9, 11–12) and one undescribed lanostane-type aglycone (10) were identified from the aerial parts of Cimicifuga yunnanensis. The new structures were elucidated by analysis of spectroscopic data. Compounds 3–5, 7–9, and 11, without obvious cytotoxicity at 50 μM, were evaluated for inhibiting the mRNA expressions of atherosclerosis-related factors of CD147 (extracellular matrix metalloproteinase inducer, EMMPRIN), matrix metalloproteinase 2 (MMP-2) and MMP-9 in phorbol-12-myristate-13-acetate (PMA) induced Human monocytic THP-1 cells by using a quantitative real-time PCR method (q-PCR). Among them, aglycones 7 and 8 showed potent activities, whereas all tested glycosides were inactive. Compounds 7 and 8 suppressed the mRNA expression of CD147 in a dose-dependent manner, with an IC50 value of 3.38 ± 0.27 μM and 8.25 ± 0.33 μM, respectively. Besides, 7 dose-related down-regulated the mRNA expression of MMP-2, and MMP-9, having an IC50 value of 6.32 ± 0.31 μM and 11.57 ± 0.23 μM, respectively. Meanwhile, 8 at 10 μM reduced the mRNA expression of MMP-2 and MMP-9 by 35% and 25%, respectively. Significantly, the migration ability of the induced THP-1 cells was potently and dose-dependently inhibited by 7, with an IC50 value of 5.87 ± 0.27 μM.

The present study investigated the therapeutic potential of omega‐6 fatty acids, according to their effects on antioxidant markers and matrix metalloproteinases (MMPs), in coronary heart disease‐induced rats. Rats were grouped into group I (sham control), group II (control), group III (0.5 g/kg bwt of omega‐6 fatty acids) and group IV (1 g/kg bwt of omega‐6 fatty acids). Reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), catalase, glutathione peroxidase (Gpx) and acetylcholinesterase (AChE) enzyme activities were determined. ROS and MDA were substantially reduced, whereas SOD, catalase, Gpx and AChE were significantly increased, following supplementation with omega‐6 fatty acids. MMP‐2 mRNA expression was drastically increased by 95% in group II. Treatment significantly reduced MMP‐2 mRNA expression by 12.3% and 26.7% in groups III and IV respectively. MMP‐9 mRNA expression drastically increased, by 121%, in group II. Treatment significantly reduced MMP‐9 mRNA expression by 22.6% and 29.4% in groups III and IV respectively. MMP‐2 protein expression was drastically increased, by 81%, in group II. Treatment significantly reduced MMP‐2 protein expression by 9.4% and 26% in groups III and IV respectively. MMP‐9 protein expression was drastically increased, by 100%, in group II. Treatment significantly reduced MMP‐9 protein expression by 18.9% and 26.9% in groups III and IV respectively. In summary, the consumption of omega‐6 fatty acids significantly decreased MDA and ROS, while SOD, catalase, GHS, Gpx and AChE were increased. Furthermore, omega‐6 fatty acids significantly downregulated MMP‐2 and MMP‐9 expression in our coronary heart disease‐induced rat model.

Tuberculosis is a devastating disease responsible for approximately 1.5 million deaths annually especially in developing countries. Although there is recommended and standard treatment for tuberculosis but the non-adherence of the patients to the lengthy treatment, adverse effects of the drugs and the emergence of multi-drug resistant strains hurdles the management of this devastating disease. This study examined the anti-mycobacterial activity of a plant derived triterpenoid, sophoradiol, against the drug-resistant strains of Mycobacterium tuberculosis and also in murine model of tuberculosis. The results showed that sophoradiol exhibits remarkable activity against the H37RV strain with an MIC of 8.5 μg/mL. The MIC of sophoradiol against the drug resistant strains of M. tuberculosis (CX1 to CX5) ranged from 9 to 16 μg/mL. Additionally, sophoradiol exhibited a bactericidal activity against H37RV strain with MBC equal to 2X MIC. Drug interaction studies showed that sophoradiol exhibits additive interaction with isoniazid and synergistic interaction with rifampicin. In the mice model of tuberculosis, sophoradiol also exhibited remarkable efficacy. Finally, cytotoxicity assays showed that sophoradiol exhibits negligible toxicity against the normal human breast cell lines. Taken together, it is concluded that sophoradiol may prove beneficial lead molecule for the management of tuberculosis.

The present study investigated the role of colchicine in the treatment of RSV infection. Treatment of BEAS-2B cells following RSV infection with colchicine caused a significant decrease in the number of viral plaques. In RSV-infected BEAS-2B cells’ treatment with colchicine leads to a significant up-regulation of both IFN-β1 and RIG-I genes. The levels of interleukin, NO, and MDA were suppressed in BEAS-2B cells infected with RSV by colchicine. The phosphorylation of Stat3, COX-2, and p38 was also suppressed significantly by colchicine. The phosphorylation of IkBα was promoted in RSV-infected BEAS-2B cells’ oncolchicine treatment. In neonatal rats, replication of RSV was inhibited significantly by colchicine treatment which was evident by suppression of RSV-L gene expression. A significant decrease in the level of IL-6 and TNF-α was caused in neonatal rat BALF by colchicine treatment. The production of MDA, NO and MPO in the neonatal rat BALF was suppressed markedly by colchicine treatment. Treatment of the neonatal rats infected by RSV with colchicine suppressed the release of IκBα and COX-2 in the pulmonary epithelial cells. Colchicine treatment of the neonatal rats promoted the expression of IFN-α and IFN-β1. In summary, the current study showed that colchicine inhibited RSV infection in neonatal rats through regulation of anti-oxidative factor production. The expression of IFN-β1 and RIG-I genes was also up-regulated in the RSV-infected alveolar epithelial cells by treatment with colchicine. Therefore, colchicine may be developed as the therapeutic agent for the treatment of RSV infection.