Ficus pandurata Hance Inhibits Ulcerative Colitis and Colitis-Associated Secondary Liver Damage of Mice by Enhancing Antioxidation Activity

Inflammatory bowel disease (IBD), a global disease threatening human health, is commonly accompanied by secondary liver damage (SLD) mediated by the gut-liver axis. Oxidative stress acts a critical role in the onset of IBD, during which excessive oxidation would destroy the tight junctions between intestinal cells, promote proinflammatory factors to penetrate, and thereby damage the intestinal mucosa. Ficus pandurata Hance (FPH) is widely used for daily health care in South China. Our previous study showed that FPH protected acute liver damage induced by alcohol. However, there is no study reporting FPH treating ulcerative colitis (UC). This study is designed to investigate whether FPH could inhibit UC and reveal its potential mechanism. The results showed that FPH significantly alleviated the UC disease symptoms including the body weight loss, disease activity index (DAI), stool consistency changing, rectal bleeding, and colon length loss of UC mice induced by dextran sulfate sodium (DSS) and reversed the influences of DSS on myeloperoxidase (MPO) and diamine oxidase activity (DAO). FPH suppressed UC via inhibiting the TLR4/MyD88/NF-κB pathway and strengthened the gut barrier of mice via increasing the expressions of ZO-1 and occludin and enhancing the colonic antioxidative stress property by increasing the levels of T-SOD and GSH-Px and the expressions of NRF2, HO-1, and NQO1 and reducing MDA level and Keap1, p22-phox, and NOX2 expressions. Furthermore, FPH significantly inhibited SLD related to colitis by reducing the abnormal levels of the liver index, ALT, AST, and cytokines including TNFα, LPS, LBP, sCD14, and IL-18 in the livers, as well as decreasing the protein expressions of NLRP3, TNFα, LBP, CD14, TLR4, MyD88, NF-κB, and p-NF-κB, suggesting that FPH alleviated UC-related SLD via suppressing inflammation mediated by inhibiting the TLR4/MyD88/NF-κB pathway. Our study firstly investigates the anticolitis pharmacological efficacy of FPH, suggesting that it can be enlarged to treat colitis and colitis-associated liver diseases in humans.

An Update on Antioxidative Stress Therapy Research for Early Brain Injury After Subarachnoid Hemorrhage

The main reasons for disability and death in aneurysmal subarachnoid hemorrhage (aSAH) may be early brain injury (EBI) and delayed cerebral ischemia (DCI). Despite studies reporting and progressing when DCI is well-treated clinically, the prognosis is not well-improved. According to the present situation, we regard EBI as the main target of future studies, and one of the key phenotype-oxidative stresses may be called for attention in EBI after laboratory subarachnoid hemorrhage (SAH). We summarized the research progress and updated the literature that has been published about the relationship between experimental and clinical SAH-induced EBI and oxidative stress (OS) in PubMed from January 2016 to June 2021. Many signaling pathways are related to the mechanism of OS in EBI after SAH. Several antioxidative stress drugs were studied and showed a protective response against EBI after SAH. The systematical study of antioxidative stress in EBI after laboratory and clinical SAH may supply us with new therapies about SAH.

Shexiang Baoxin Pill for Acute Myocardial Infarction: Clinical Evidence and Molecular Mechanism of Antioxidative Stress

Acute myocardial infarction (AMI) has been a preclinical and clinical concern due to high hospitalization rate and mortality. This study was aimed at evaluating the effectiveness and safety of Shexiang Baoxin Pill (SBP) for AMI and exploring the possible mechanism of oxidative stress. Six databases were searched on March 26, 2021. Twenty-four studies were included and accessed by the RoB 2.0 or SYRCLE tool. Compared with routine treatment (RT), SBP showed the effectiveness in the clinical efficacy ( RR = 1.15 , 95% CI [1.06, 1.25]), left ventricular ejection fraction (LVEF) ( SMD = 0.73 , 95% CI [0.62, 0.95]), glutathione (GSH) ( SMD = 2.07 , 95% CI [1.51, 2.64]), superoxide dismutase (SOD) ( SMD = 0.92 , 95% CI [0.58, 1.26]), malondialdehyde (MDA) ( SMD = − 4.23 , 95% CI [-5.80, -2.66]), creatine kinase-myocardial band (CK-MB) ( SMD = − 4.98 , 95% CI [-5.64, -4.33]), cardiac troponin I (cTnI) ( SMD = − 2.17 , 95% CI [-2.57, -1.76]), high-sensitivity C-reactive protein (Hs-CRP) ( SMD = − 1.34 , 95% CI [-1.56, -1.12]), interleukin-6 (IL-6) ( SMD = − 0.99 , 95% CI [-1.26, -0.71]), triglycerides (TG) ( SMD = − 0.52 , 95% CI [-0.83, -0.22]), flow-mediated dilation (FMD) ( SMD = 1.39 , 95% CI [1.06, 1.72]), von Willebrand Factor (vWF) ( SMD = − 1.77 , 95% CI [-2.39, -1.15]), nitric oxide (NO) ( SMD = 0.89 , 95% CI [0.65, 1.13]), and recurrent rate ( RR = 0.30 , 95% CI [0.15, 0.59]). But SBP adjunctive to RT plus PCI had no improvements in almost pooled outcomes except for the Hs-CRP ( SMD = − 1.19 , 95% CI [-1.44, -0.94]) and TG ( SMD = − 0.25 , 95% CI [-0.48, -0.02]). Laboratory findings showed that SBP enhanced the endothelial nitric oxide synthase (eNOS) activity and regulated laboratory indexes especially for homocysteine. In conclusion, SBP has adjunctive effects on AMI via the mechanism of antioxidative stress. The current evidence supports the use of SBP for mild and moderate AMI patients.

Benefits of the Phytoestrogen Resveratrol for Perimenopausal Women

Endometriosis, characterized by macroscopic lesions in the ovaries, is a serious problem for women who desire conception. Damage to the ovarian cortex is inevitable when lesions are removed via surgery, which finally decreases the ovarian reserve, thereby accelerating the transition to the menopausal state. Soon after cessation of ovarian function, in addition to climacteric symptoms, dyslipidemia and osteopenia are known to occur in women aged >50 years. Epidemiologically, there are sex-related differences in the frequencies of dyslipidemia, hypertension, and osteoporosis. Females are more susceptible to these diseases, prevention of which is important for healthy life expectancy. Dyslipidemia and hypertension are associated with the progression of arteriosclerosis, and arteriosclerotic changes in the large and middle blood vessels are one of the main causes of myocardial and cerebral infarctions. Osteoporosis is associated with aberrant fractures in the spine and hip, which may confine the patients to the bed for long durations. Bone resorption is accelerated by activated osteoclasts, and rapid bone remodeling reduces bone mineral density. Resveratrol, a plant-derived molecule that promotes the function and expression of the sirtuin, SIRT1, has been attracting attention, and many reports have shown that resveratrol might exert cardiovascular protective effects. Preclinical reports also indicate that it can prevent bone loss and endometriosis. In this review, I have described the possible protective effects of resveratrol against arteriosclerosis, osteoporosis, and endometriosis because of its wide-ranging functions, including anti-inflammatory and antioxidative stress functions. As ovarian function inevitably declines after 40 years, intake of resveratrol can be beneficial for women with endometriosis aged <40 years.

The Effects of Two Nrf2 Activators, Bardoxolone Methyl and Omaveloxolone, on Retinal Ganglion Cell Survival during Ischemic Optic Neuropathy

Nonarteritic anterior ischemic optic neuropathy (NAION) is one of the most common acute optic neuropathies that affect the over 55-year-old population. NAION causes the loss of visual function, and it has no safe and effective therapy. Bardoxolone methyl (methyl 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate; CDDO-Me; RTA 402) is a semisynthetic triterpenoid with effects against antioxidative stress and inflammation in neurodegeneration and kidney disease that activates the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Moreover, RTA 402 is an FDA-approved compound for the treatment of solid tumors, lymphoid malignancies, melanoma, and chronic kidney disease. Omaveloxolone (RTA 408) is an activator of Nrf2 and an inhibitor of NFκB, possessing antioxidative and anti-inflammatory activities in mitochondrial bioenergetics. RTA 408 is also under clinical investigation for Friedreich ataxia (FA). In this study, a rodent anterior ischemic optic neuropathy (rAION) model induced by photothrombosis was used to examine the therapeutic effects of RTA 402 and RTA 408. Treatment with RTA402 results in antiapoptotic, antioxidative stress, anti-inflammatory, and myelin-preserving effects on retinal ganglion cell (RGC) survival and visual function via regulation of NQO1 and HO-1, reduced IL-6 and Iba1 expression in macrophages, and promoted microglial expression of TGF-β and Ym1 + 2 in the retina and optic nerve. However, these effects were not observed after RTA 408 treatment. Our results provide explicit evidence that RTA 402 modulates the Nrf2 and NFκB signaling pathways to protect RGCs from apoptosis and maintain the visual function in an rAION model. These findings indicate that RTA 402 may a potential therapeutic agent for ischemic optic neuropathy.

Multiple exposures to high concentration of selenate significantly improve selenate tolerability, red elemental selenium (Se0) and selenoprotein biosynthesis in Herbaspirillum camelliae WT00C

Herbaspirillum camelliae WT00C isolated from tea plant has an intact selenate metabolism pathway but its selenate tolerability is poor. In this study, microbiological properties between the strain WT00C and three strains CT00C, NCT00C and NT00C obtained respectively from 4, 6 and 8 rounds of 24-h exposures to 200 mM selenate were studied and compared. The selenate tolerability and the capability of generating red elemental selenium (Se0) and selenoproteins were significantly improved in H. camelliae WT00C via 4–6 rounds of multiple exposures to high concentration of selenate. The original strain WT00C grew in 200 mM selenate with the lag phase of 12 h and 400 mM selenate with the lag phase of 60 h, whereas the strains CT00C and NCT00C grew in 800 mM selenate and showed quite short lag phase when they grew in 50–400 mM selenate. Two stains also significantly improved the biosynthesis of red elemental selenium (Se0) and selenoproteins besides selenate tolerance. The stains CT00C and NCT00C exhibited more than 30% selenium conversion efficiency and 40% selenoprotein biosynthesis as compared to the original strain WT00C. These characteristics of the strains CT00C and NCT00C make them possible to be applied in pharmaceuticals and feed industries. The strain NT00C obtained from 8 rounds of 24-h exposures to 200 mM selenate was unable to grow in ≥ 400 mM selenate, and its selenium conversion efficiency and selenoprotein biosynthesis were similar to the strain WT00C. Too many exposures caused gene inactivation of some key enzymes involving in selenate metabolism and antioxidative stress. In addition, bacterial cells underwent obviously physiological and morphological changes including gene activity, cell enlargement and surface-roughness alterations during the process of multiple exposures to high concentration of selenate.

NMDA Receptor Mediates the Anticonvulsant Effect of Hydroalcoholic Extract of Artemisia persica in PTZ-Induced Seizure in Mice

It is necessary to seek more effective sources to design new drug against epilepsy. This study aimed to evaluate the effect of hydroalcoholic extract of Artemisia persica on pentylenetetrazole- (PTZ-) induced seizure in male mice by investigating the possible role of the NMDA receptor and antioxidative stress effect. The phenolic profile of A. persica extract was determined by HPLC-DAD analysis. Mice were treated with normal saline or A. persica extract or pentobarbital or a subeffective dose of extract plus ketamine (NMDA receptor antagonist) and/or effective dose of extract plus NMDA. PTZ (90 mg/kg) was injected intravenously for induction of seizure. The seizure threshold was measured. Then mice were euthanized and the antioxidant capacity and the level of malondialdehyde (MDA) of the prefrontal cortex and serum were measured. The gene expression of NMDA receptor subunits (Nr2a and Nr2b) was determined by real-time PCR. Findings showed that A. persica extract increased the seizure threshold, increased antioxidant capacity, and decreased MDA levels in the serum and brain samples. A. persica extract reduced the expression of NMDA receptor subunits. The result showed that ketamine potentiated the effect of the subeffective dose of extract. HPLC analysis showed that quercetin had the highest flavonoid content and also caffeic acid had the highest content of the phenolic acids. A. persica extract probably via NMDA receptor exerts anticonvulsant properties.